PMID- 3324157 TI - Multi-infarct dementia: diagnosis and management. Infarctions produce 20% to 35% of severe dementia cases. PMID- 3324158 TI - Edward G. Billings, M.D.: pioneer of consultation-liaison psychiatry. PMID- 3324159 TI - Pharmacotherapy of social phobia. A condition distinct from panic attacks. PMID- 3324160 TI - Should psychotherapy be considered a biological treatment? PMID- 3324161 TI - Panic disorder in patients with angiographically normal coronary arteries. A pilot study. PMID- 3324162 TI - Sequence-specific assignments and their use in NMR studies of DNA structure. PMID- 3324163 TI - Pharmacologic management of migraine headaches. PMID- 3324164 TI - [Recent advances in the research of hemopoietic factors in relation to cancer]. PMID- 3324165 TI - [Dynamic reciprocity between cell and extracellular matrix]. PMID- 3324166 TI - [Chromosome banding patterns of higher vertebrates and nucleotide sequences of their genes]. PMID- 3324167 TI - [Bioluminescence: principles and applications]. PMID- 3324168 TI - Inhibition of adenosine diphosphate-induced intravascular aggregation of rat platelets in vivo by 6-oxo-prostaglandin E1. AB - The antiaggregatory effects of 6-oxo-PGE1 were evaluated in vivo in the rat using a minimally invasive technique involving 111-Indium labelling of platelets. The antiaggregatory effects on adenosine diphosphate-induced aggregation were compared with those of prostacyclin (PGI2) and prostaglandin E1 (PGE1) following slow infusions and bolus injections. The rank order of antiaggregatory potency was PGI2 greater than 6-oxo-PGE1 greater than PGE1 while the rank order of duration of antiaggregatory effects was PGE1 greater than 6-oxo-PGE1 greater than PGI2. The kinetics of the antiaggregatory effects of these prostaglandins suggests that such actions are not mediated by direct effects on platelets, but through a secondary mechanism. PMID- 3324169 TI - Prostacyclin and thromboxane release from the vessel wall--comparison between an incubation and a perfusion model. AB - Prostacyclin (measured as its stable degradation product 6-keto-PGF1 alpha) and thromboxane (measured as its stable degradation product TxB2) produced by the vascular wall were measured by radioimmunoassay (RIA). Four pieces from the rabbit aorta and four from the caval vein were used. One piece was incubated in Hank's balanced salt solution (HBSS), one piece with additional indomethacin, and the other pieces were mounted in a perfusion system so that only the endothelium was exposed to the buffer solution with or without indomethacin. There was a higher release in the piece incubated in the buffer than in the piece which was perfused, indicating that not only the endothelium releases prostacyclin and thromboxane from the vascular wall. The 6-keto-PGF1 alpha/TxB2 ratio was higher in the perfused than in the incubated samples suggesting that 6-keto-PGF1 alpha release is higher in the endothelium than in the other wall layers and/or that TxB2 production is higher in the outer layers than in the inner layers. No correlation was found between the release from the incubated vessel and from the perfused vessel. There was a higher release of 6-keto-PGF1 alpha from aortas than from caval veins, when incubated or perfused, whereas there was a tendency to a higher release of TxB2 from veins than aortas. PMID- 3324170 TI - Urinary prostaglandin E2 excretion in renal allotransplantation in man. AB - The urinary prostaglandin E2 excretion was measured daily for 28 days in 15 patients (10 men and 5 women) after renal allotransplantation. Patients with acute oliguric renal failure immediately after the transplantation showed high urinary PGE2 concentrations, but no or minimal increase in the total excretion rates. The median PGE2 excretion was 211 micrograms/24 h after establishment of stable renal function, but with great individual variations. Rejection crises were characterized by a two-fold increase in PGE2 excretion, with a subsequent fall induced by the steroid treatment. The PGE2 excretion correlated better with urinary sodium excretion than diuresis. PMID- 3324172 TI - [A vaccine against malaria]. PMID- 3324171 TI - Synthesis of prostaglandins, TXA2 and PGI2, during one lung anesthesia. AB - This study is to determine histamine, serotonin, TXA2 and PGI2 to be the cause of Hypoxic Pulmonary Vasoconstriction (HPV) at the same time of one lung ventilation and thoracotomy. Five patients who were to undergo upper-lobe resection of the right lung, were included in this study. All patients underwent same premedication and anesthetic method. Endotracheal intubation was done with a Univent tracheal tube. Gas analysis and determinations of the substances were done at six times in total. Respiratory Index (RI) began to increase immediately after the start of one lung ventilation. Post-thoracotomy RI further increased. After closing of the thorax, RI returned to the control values. Serotonin and histamine showed no change in any case throughout the experiment. TXB2 began to increase along with the start of one lung ventilation. The 15-min value was 167.2 +/- 85.8 pg/ml and 30-min value was 345.6 +/- 261.2 pg/ml, showing significant increase. The values of 6-keto PGF1 alpha were 22.6 +/- 2.9 pg/ml (15-min value), 89.6 +/- 52.3 pg/ml (30-min value), 290.8 +/- 120.1 pg/ml (post opening value) and 84.4 +/- 21.3 pg/ml (post-closing value). In our study, we concluded that neither serotonin nor histamine was the direct factor of HPV. TXA2 was the direct chemical mediator of HPV and PGI2 showed a negative feedback to the pulmonary vasoconstriction. PMID- 3324174 TI - Borderline personality disorder: validity revisited. PMID- 3324173 TI - [Drug resistance of Proteus vulgaris, Proteus morganii and Providencia rettgeri isolated from diagnostic specimens]. PMID- 3324175 TI - Lithium therapy revisited. PMID- 3324176 TI - Changes in DST before and after a bone marrow transplant conditioning regimen: a pilot study. PMID- 3324177 TI - Sleep laboratory assessment of normal sleep and sleep disorders. PMID- 3324178 TI - Sleep in psychiatric disorders. PMID- 3324179 TI - Sleep disorders in medical illness. PMID- 3324180 TI - Sleep disorders in children. PMID- 3324181 TI - Sleep disorders in the elderly. PMID- 3324182 TI - Role of the sleep laboratory in the evaluation of impotence. PMID- 3324183 TI - Insomnia in hospitalized patients: approaches to management. PMID- 3324184 TI - Treatment of sleep disorders. PMID- 3324185 TI - Is there a dementia of schizophrenia? PMID- 3324186 TI - Psychiatric morbidity in heart patients. PMID- 3324188 TI - Current and future perspectives on psychiatric involvement in bone marrow transplantations. PMID- 3324187 TI - Psychiatric aspects of bone marrow transplantation: a review and current issues. AB - BMT represents a major medical advance and offers to most individuals who undergo this procedure the only hope for long term survival. The current psychiatric literature is anecdotal and mostly restricted to discussion of psychiatric issues related to the BMT hospitalization itself. There is substantial agreement about the important psychiatric issues concerning BMT recipients, their families, and the BMT team. However, many post-BMT hospitalization psychiatric and psychosocial issues need attention: the psychological impact of being a BM donor, the consequences of BMT for donor-recipient relationships, the long-term family consequences of BMT, and the long-term cognitive, neuroendocrine, sexual/reproductive, and psychosocial status of BMT survivors. Hopefully, these issues will be increasingly rigorously and effectively addressed in the near future, so that effective psychiatric and psychosocial interventions can be developed which maximize the psychosocial outcome of those affected by BMT. PMID- 3324189 TI - Clinical EEG correlates of anorexia and bulimia: historical review and current findings. PMID- 3324190 TI - Psychogeriatrics: the relationship between consultation-liaison and inpatient psychiatry. PMID- 3324191 TI - Ethical issues in inpatient practice. PMID- 3324192 TI - Legal problems in inpatient psychiatry. AB - This paper has discussed broadly a panorama of legal issues which may arise in the practice of inpatient psychiatry. Such a discussion can only be general and may not apply in a specific jurisdiction. Psychiatrists in inpatient settings should be familiar with all the issues raised and with local practices. Psychiatry is a field of medicine with a multitude of legal problems, more so than other medical specialties. Psychiatrists therefore have the obligation to themselves, their hospitals, and their patients to be cognizant of the legal issues in psychiatric practice. Hopefully, the more that they know, the less likely they are to be confronted with claims that they did not pay attention to this essential aspect of inpatient psychiatric practice. PMID- 3324193 TI - [Oliver Wendell Holmes--an outstanding American physician and writer]. PMID- 3324194 TI - [Dynamic pulmonary scintigraphy with Tc99m radioaerosol for the evaluation of the permeability of the alveolo-capillary barrier]. AB - Pulmonary clearance of small droplet 99mTc-DTPA radioaerosol was studied in 100 patients (12 normal subjects, N; 10 asymptomatic healthy smokers, FA; 31 patients with interstitial lung diseases, IP; 47 patients with chronic obstructive lung disease, BPCO). The first seven minutes of clearance were described with the function At = Ao*exp (-K*t) and the time constant K was considered representative of the 99mTc-DTPA clearance rate and hence of the alveolar-capillary barrier permeability. Groups FA, IP and BPCO showed a significant (p less than 0.05) or a highly significant (p less than 0.01) increase in permeability when compared to group N. No correlation was found between permeability and bronchial obstruction tests. The following conclusions were drawn: --99mTc-DTPA dynamic lung scanning is an easy, non-invasive method to assess derangements of alveolar-capillary barrier permeability secondary to epithelial damage; --permeability increase is a very early effect of cigarette smoke damage to the epithelium; --other mechanisms of epithelial injury are present in diffuse lung disease; --while the clinical role of this new pathophysiological test is not yet clear, it is likely that it may become a very early marker of pulmonary epithelial damage in diffuse lung disease. PMID- 3324195 TI - [Ultrasonic diagnosis of the central hyperechogenic area in lymph nodes. A sign of benign lymphadenopathy]. AB - When identifying superficial lymphadenopathies by means of echotomography, the only accepted criterium of evaluation is still dimension. Only lymph nodes with a diameter longer than 0.5 cm are considered as potentially pathological, irrespective of their morphological characteristics. In the past two years an echotomographic study of the surface regions was carried out on 300 patients. Some suffered from unspecific solitary lymphadenopathies; most of the others were affected by stationary neoplasias, mainly situated in the cervical region. In many cases it has been possible to correlate the echotomographic and the histological results. Sixty-nine out of the 300 examined patients had lymph nodes with a central hyperechogenic area. Histology showed these lymph nodes to be the site of reactive hyperplasia. This characteristic has never been found in neoplastic lymph nodes. It has been hypothesized that this spot corresponds to the hilus of the lymph node and that, through its identification, it may be possible to distinguish benign from neoplastic lymph nodes. PMID- 3324196 TI - [Structuring and use in clinical research of a software for the diagnosis and features of polypoid lesions of the colorectum]. AB - Double contrast enema and endoscopy are very important in the diagnosis of adenomas and early cancer of the colon and rectum. These exams can not only detect the presence, but also suggest the histologic diagnosis, of polypoid lesions of the colon. An Olivetti M24 Personal Computer was used to create a software to study the results obtained by double contrast enema, and to compare them with endoscopy and pathology. The data base is formed by 7 files: one anagraphic, 3 collecting the characteristics of the diagnosis--namely the radiologic, the endoscopic and the pathologic one-- and 3 multiple files featuring each lesion, as defined by the three diagnostic techniques. The software allows to evaluate the different lesions that can be detected by the three techniques in the same patient and to compare the diagnosis of presence to the morphologic features of each lesion. False negatives and false positives of each technique are easily recognized. It is also possible to characterize the single morphologic feature leading the radiologist and/or the endoscopist to express an opinion about the histologic diagnosis of each lesion and to compare them with pathological features. The first experience in clinical use of the software, in the analysis of the characters of 336 lesions in 218 patients, is described. PMID- 3324197 TI - [Comparison of ultrasound and radiology in the intraoperative diagnosis of nephrolithiasis]. AB - Both intraoperative ultrasonography and radiology were utilized as a surgical aid while operating on 53 patients with renal lithiasis. A thorough comparison was made between the two imaging techniques: intraoperative US showed higher levels of sensitivity and accuracy, while specificity was maximal in intraoperative radiology. Intraoperative US proved to be a versatile and safe diagnostic procedure--as well as easy and quick to perform--whose accuracy in localizing stones as well as residual fragments appeared to be extremely high. Intraoperative US assistance during surgical procedures for renal lithiasis proves thus to be of the utmost importance in urologic practice. PMID- 3324198 TI - [Castleman's pseudolymphoma. Reliability of diagnostic imaging methods and presentation of a rare case]. PMID- 3324199 TI - [Giuseppe Longo (1907-1987)]. PMID- 3324200 TI - The pathogenesis of rheumatoid arthritis. A critical assessment of the role of autologous stimulation in the perpetuation of rheumatoid synovitis. AB - Current models for rheumatoid arthritis emphasize the role of activated T cells and their products in the pathogenesis of synovitis. The data supporting this view are critically reviewed in this article and inconsistencies are discussed. To resolve these contradictions, the authors propose that rheumatoid synovitis represents a localized autologous mixed lymphocyte reaction. PMID- 3324201 TI - The HLA complex and its relationship to rheumatic diseases. AB - The HLA complex has been shown to be involved in the regulation of several aspects of the immune response, and has been shown to be associated with several rheumatologic diseases. The mechanisms by which HLA molecules predispose to disease has been an area of intense interest. Recent work has provided some possible explanations for the lack of absolute associations between a particular disease and a particular HLA antigen. There is now some evidence to suggest that specific epitopes rather than entire class I or II molecules may be responsible for disease predisposition. Furthermore, it appears that these epitopes may be transferred between different class I and II molecules by a mechanism known as gene conversion. Work evaluating the influence of other genes, such as those for the T cell receptor, on disease susceptibility has just begun. Many of the rheumatic diseases are quite diverse in their presentation. If only one of a heterogeneous group of diseases is associated with an HLA antigen, study of the entire group of diseases will of necessity dilute the association. Better definitions of clinical subsets should lead to improved correlations of HLA and disease. Little is known of etiologic agents or pathogenesis. As our knowledge of the interaction of HLA antigens, T cell receptors, and etiologic agents increases, we will come closer to an understanding of the mechanisms by which these molecules predispose to disease. PMID- 3324202 TI - The genetics of rheumatic disease in man. AB - This article reviews the current knowledge of genetic factors conferring susceptibility to several major rheumatic disorders, in particular, rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), systemic lupus erythematosus (SLE), and Sjogren's syndrome. Emphasis is given to major histocompatibility complex associations with these diseases, particularly rapidly evolving knowledge of class II HLA genes and disease-conferring "epitopes." Non-MHC-linked genes, such as T cell receptor and immunoglobulin genes, also may be involved. PMID- 3324204 TI - Progress in the understanding of inducible models of chronic arthritis. AB - Definitive information regarding the etiology of most rheumatic syndromes is not available, but studies of several inducible models of chronic arthritis have helped to identify pathogenetic mechanisms in human inflammatory arthritis. Animal models offer an opportunity to analyze morphologic and biochemical changes occurring during the course of an arthritis, probe the role of genetics, and predict the effects of therapeutic interventions in the human disease. This article describes some contributions obtained from animal studies. PMID- 3324203 TI - Genomic organization and expression of B and T cell antigen receptor genes in murine lupus. AB - Studies with genomic DNAs of lupus mice and monoclonal autoantibodies suggest that autoantibody expression does not result from defects in immunoglobulin germline genes nor in mechanisms generating antibody repertoires. Genomic and expression abnormalities of T cell antigen receptor genes have been identified in lupus mice, but their possible contribution to disease manifestations remains to be established. PMID- 3324205 TI - Rheumatoid factor. AB - Many human RF-associated crossreactive idiotypes (CRIs) have been defined. Since these CRIs probably are the phenotypic markers of Ig variable region genes, the data suggest that human RFs employ several Ig variable region genes which are common among outbred human populations. There are at least four types of stimuli which can trigger RF production. They are aggregated IgG in the form of antigen antibody complexes, exogenous antigens bearing cross-reactive determinants to human IgG, autologous antibodies which mimic the Fc region of human IgG, and polyclonal B cell activators. Transient RF secretion is regularly induced by antigen-antibody complexes during secondary immune responses. In normal human subjects, RFs may be produced primarily by the B cells which bind mouse red cells, or express Leu l markers on their surface. Leu l is the human homolog of Ly l in mice. Upon polyclonal stimulation, these Ly l B cells secrete IgM autoantibodies. Combined protein and DNA sequencing studies reveal that human RFs utilize a small number of light chain variable region genes, together with several heavy chain variable regions genes. In contrast, by mRNA sequencing, murine RFs were found to employ many heavy and light chain variable region genes which belong to various gene families. Two human RF-related light chain variable region genes have been cloned and characterized. One germ-line Vk gene (designated Humkv325) is identical to four RF light chain sequences from unrelated individuals, and differs from the other eight RF light chains by one to seven amino acid residues. These results demonstrate that this RF-related Vk gene is both widely distributed and conserved among outbred human populations. PMID- 3324206 TI - Mechanisms of antinuclear antibody production in the rheumatic diseases. AB - Recent investigations on the mechanisms of ANA production in the rheumatic diseases suggest that these responses frequently emerge in the setting of nonspecific immunoregulatory disturbances. However, the expansion and maturation of these responses to generate pathogenic specificities may require the coexistence of clonal or antigen-specific abnormalities. At the genetic level, ANAs appear to be of diverse origin, including some with representation in the normal B cell repertoire. Since some ANAs are disease-specific, elucidation of the basis of their production should provide insights into the unique pathogenetic features of different rheumatic diseases. PMID- 3324207 TI - Immune complexes in the rheumatic diseases. AB - This article reviews the intrinsic characteristics of immune complexes important in determining tissue deposition and the properties of the two arms of receptor mediated handling of immune complexes in the circulation. The interrelationships between complement receptor (CRl) and Fc receptor mechanisms, including abnormalities found in rheumatic diseases, are discussed as contributing factors to immune complex disease pathogenesis. PMID- 3324208 TI - Differential scanning calorimetry of membrane proteins. PMID- 3324209 TI - Cell membrane proteins. An overview. PMID- 3324210 TI - Probing molecular dynamics of proteins in biological membranes by optical spectroscopy: rotational diffusion. PMID- 3324211 TI - The uncoupling protein from brown adipose tissue mitochondria. PMID- 3324212 TI - Determinisms of odontogenesis. PMID- 3324213 TI - Medical applications of monoclonal antibodies. AB - Since the first publication of the production of monoclonal antibodies in 1975 there has been enormous interest in the possible medical applications. Monoclonal antibodies are now widely used in all areas of biological and medical research as well as in clinical diagnostic tests and in therapy. This review concentrates on the clinical use of antibodies in therapy particularly with regard to the properties of the antibodies which seem most relevant to their usefulness. In vitro tests using human effector systems and in-vivo animal models have demonstrated the importance of the antibody isotype and valency for antigen as well as the specificity of binding. With the appropriate choice of antibody, used either alone, or conjugated to radioisotopes, drugs or toxins, it is possible to specifically deplete subpopulations of cells both in-vitro and in-vivo. Such antibodies can be used for tumour therapy, and for immunosuppression in organ transplantation and in autoimmune disorders. PMID- 3324214 TI - [The centenary of the birth of Gaspar Vianna]. PMID- 3324216 TI - [Natural infection of triatomines in Espiritu Santo with flagellates morphologically similar to Trypanosoma cruzi]. PMID- 3324215 TI - The discovery of urea stibamine. PMID- 3324217 TI - [The use of non-precious metal alloys for dental crowns and bridges]. PMID- 3324218 TI - [Marginal notes on the anatomy of the masticatory system according to Govert Bidloo (1685) and William Cowper (1698)]. PMID- 3324219 TI - [Breeding of Akodon arviculoides (Rodentia, Cricetidae) in the laboratory]. PMID- 3324220 TI - [Long-term results of tibiofibular grafts in the treatment of septic pseudarthroses of the leg]. PMID- 3324222 TI - [Treatment of Parker and Jackson lymphosarcoma]. PMID- 3324221 TI - [Treatment of compound fractures of the leg using pedicled or free muscle flaps and supplemental bone grafts]. PMID- 3324223 TI - [Adjuvant treatment of osteosarcomas. Experience of the Group for the Study of Bone Tumors]. PMID- 3324224 TI - [Prospective studies on 73 cases of boutonneuse fever. Validity of the clinico epidemiological diagnosis and serology with respect to Proteus]. PMID- 3324225 TI - [Determination of beta-2-microglobulin levels in patients with systemic lupus erythematosus: correlation with clinical and biological parameters]. PMID- 3324226 TI - [Ankylosing spondylitis and cardiopathy]. PMID- 3324227 TI - [Control of malaria in Africa: from the eradication of malaria to the control of malaria]. AB - The control strategies usually recommended in Africa south of the Sahara have not been followed by a lasting decline in the endemic level of the disease in the rural environment. The set-backs of the eradication period have revealed the need to redefine control objectives and strategies adapted to each type of malaria. Systematic chemotherapy for attacks of fever is a strategy that can be proposed in all circumstances; it avoids mortality from malaria; it can be carried out in the field on a country scale. The other means of control, directed against the parasites and the vectors, may be used depending of the specific situation in each country and on each type of malaria. Malaria control has to be integrated into the basic health system of each country, and we need to improve health education and develop primary health care. We must continue with our efforts to develop new antimalarial drugs, insecticides and vaccines; urgent steps must be taken to train malariologists capable of adapting the new techniques to the actual situation in the field. It is by associating socioeconomic development with the control means as a whole that we shall be able to control the various types of malaria and to reach out towards the objective of health for all by the year 2000. PMID- 3324228 TI - [Review of statistical procedures for determining the equivalency of two treatments]. AB - The absence of a significant difference in a classical efficacy trial testing the null hypothesis of equality between N and S does not allow us to conclude that the treatments are equivalent. Testing the null hypothesis of N not equivalent to S requires: specifying the definition of "equivalence" by choosing delta L, the upper allowable value of the actual difference between two equivalent treatments. The appropriate statistic D which evaluates the difference between N and S, has a non central distribution under the null hypothesis of inequivalence (Ko:[E(D)] greater than or equal to delta L, two-sided test). Under the null hypothesis for a two-sided test, parameters of noncentral distribution have to be estimated, and the critical p-value is obtained using some approximation. Confidence interval of the true difference delta can also provide a decision rule. Specific calculation of the minimum number of subjects is required when designing an equivalence trial. PMID- 3324229 TI - [Home mechanical ventilation in Duchenne de Boulogne muscular dystrophy. Mandatory ventilation and preventive ventilation]. PMID- 3324230 TI - [Obstructive bronchiolitis]. AB - The term "obstructive bronchiolitis" used in this review covers different clinicopathological aspects. On the one hand, it refers to "small airways disease", where bronchiolar narrowings are widespread, secondary to post inflammatory fibrotic changes linked to tobacco smoke or fibrogenic dust inhalation. These obstructive changes at the level of small airways are responsible for a fixed airflow limitation. The specificity and sensibility of functional tests designed for early detection of such an obstruction (the frequency dependence of compliance, the nitrogen slope and the density dependence of the flow-volume curve) are still controversial. On the other hand, the entity covers a disease described at the beginning of the century under the name "bronchiolitis obliterans". It usually appears as a consequence of various causes: viral infection, toxins acting either inhalation or by systemic route, immunological mechanisms as in connective tissue diseases or in graft versus host reactions. A special emphasis is put on idiopathic bronchiolitis obliterans associated with organizing pneumonia. Some clinicopathologic correlations are of basic interest in relation to etiological factors: bronchiolitis obliterans due to viral infection in children involving mainly membranous bronchioles; by contrast, bronchiolitis obliterans related to other causes seems to extend further down from the terminal bronchioles to the respiratory bronchioles. Lymphoid bronchiolitis appears non specific and is mostly observed in association with systemic connective tissue diseases, such as rheumatoid arthritis. PMID- 3324231 TI - [Bronchial provocation tests using hyperventilation]. AB - The appearance of an asthmatic crisis in the minutes following physical exercise is common in symptomatic asthma. Exercise induced asthma (EIA) is linked to hyperventilation; voluntary isocapnic hyperventilation is capable of triggering a crisis. It is well established at present that EIA and post-hyperventilation asthma (HIA) are triggered by a rise in heat and water loss by the airways, which is inherent in hyperventilation. The respective role of water loss and cooling the airways are uncertain but one tends to think at the present time that the primary stimulus is the variation in osmolality of the liquid lining the epithelium. However, a relationship between the quantity of energy dissipated in the airways and the severity of EIA or HIA exists, although it is less tight than was once thought. This is perhaps not surprising, as the intermediary mechanisms connecting the stimulus to the response of the airways are poorly understood. All in all physical exercise and isocapnic hyperventilation of dry air and possibly cold air are useful and equivalent non-specific bronchial provocation tests, if only the ventilation and physical properties of the inhaled air are the same. Hyperventilation lends itself better than exercise to establishing dose-effect curves linking bronchial response to minute ventilation. Recommendations concerning the interruption of drugs, the measurement of the response and the assessment of the results are the same as with other non specific bronchial provocation tests with irritant substances or pharmacological agents. PMID- 3324232 TI - [Bronchiolitis caused by graft versus host reaction after bone marrow allograft]. AB - Graft versus host reaction (GVH) is a major complication of allogenic marrow transplants. The GVH present is a pluri-visceral syndrome in which certain pulmonary disorders are recognised. Amongst these respiratory failure by bronchiolitis is not an exceptional presentation. The case reported here is of an 18 year old man who developed, immediately following a marrow graft for acute lymphoblastic leukaemia, a lethal obstructive respiratory failure after progression for 2 1/2 years. The respiratory function data (TVO with elevated residual volume (VR) and VR/Total lung capacity (CT) hypoxia which corrected on exercise with normocapnia then hypoxic hypercapnia; compliance normal at low frequency but fell at high frequency and inspiratory and expiratory resistance was raised: DLCO/VA was normal) allowed the confirmation of obstructive respiratory failure by disease of the small airways. The pathogenesis of CVH is equivocal. Recurring infections seem to play a role, favoured by iatrogenic factors such as chemotherapy and total body irradiation. In the case reported here the first pulmonary signs followed an episode of influenza with sero conversion. PMID- 3324233 TI - [New imaging methods in the diagnosis of carcinoma of the gallbladder]. PMID- 3324234 TI - [So-called idiopathic pulmonary hemosiderosis: disease or syndrome?]. PMID- 3324235 TI - [Pancreatic polypeptide]. PMID- 3324236 TI - [Effects of sequentially administered or combined muzolimine and furosemide on water and solute excretion: quantitative and qualitative aspects]. PMID- 3324237 TI - [Immunosuppressive therapy in type 1 diabetes: update]. PMID- 3324238 TI - [Sleep disorders]. PMID- 3324239 TI - Degradation of glomerular basement membrane in diabetes. I. Susceptibility of diabetic and nondiabetic basement membrane to proteolytic degradation of isolated glomeruli. AB - Degradation of glomerular basement membrane in diabetic and nondiabetic rats was measured by incubating isolated basement membrane with a homogenate of glomeruli obtained from metabolically healthy rats. When diabetic basement membrane was used, there was a marked decrease in the amount of collagen-typical (hydroxyproline, hydroxylysine, glycine) and noncollagen-typical amino acids (proline, lysine, leucine) released in the supernatant of the incubation assay. A negative correlation was found between the amount of collagen-typical amino acids released by diabetic basement membrane and the duration of diabetes. The results indicate that the collagenous and noncollagenous peptides of diabetic basement membrane are less susceptible to proteolytic degradation than those of nondiabetic controls. This may be due to increased nonenzymatic glycosylation of diabetic basement membrane. PMID- 3324240 TI - Degradation of glomerular basement membrane in diabetes. II. Proteolytic activity of diabetic and nondiabetic glomeruli. AB - The proteolytic effects of isolated glomeruli of diabetic rats on glomerular basement membrane of nondiabetic rats was investigated at various times after streptozotocin injection. One week after induction of diabetes, proteolytic activity remained unchanged as compared with nondiabetic controls. However, 4 and 10 weeks after streptozotocin injection, glomerular degradation of collagenous (but not noncollagenous) peptides of basement membranes increased (+24% as compared with control experiments). Using diabetic basement membrane as substrate, degradation of collagenous and noncollagenous peptides caused by diabetic glomeruli was 2.6-fold and 1.7-fold higher than in control experiments with nondiabetic glomeruli. The results indicate that the disturbed degradation of glomerular basement membrane in diabetes is not due to a decreased activity of glomerular proteolytic enzymes. In contrast, it can be concluded that the increased resistance of diabetic basement membrane to proteolytic degradation could be partially compensated by quantitative and qualitative changes of the proteolytic potential of diabetic glomeruli. PMID- 3324241 TI - Non-Hodgkin's lymphoma causing fundus picture simulating fundus flavimaculatus. AB - Two apparently healthy patients experienced visual loss and had a peculiar flecked retina simulating fundus flavimaculatus in one eye some months before developing signs and symptoms of the systemic form of non-Hodgkin's large-cell lymphoma. Both experienced spontaneous improvement in visual symptoms and partial resolution of the fundus changes. PMID- 3324242 TI - Normal pubescent growth and sexual maturation. PMID- 3324243 TI - Growth and pubertal pattern in insulin dependent diabetes mellitus. PMID- 3324244 TI - Turner syndrome: a recognizable cause of adolescent short stature. PMID- 3324245 TI - Nutritional dwarfing in adolescents. PMID- 3324246 TI - Constitutional delay in growth and development. PMID- 3324247 TI - Excessive growth. PMID- 3324248 TI - Growth hormone: diagnostic and therapeutic dilemmas. PMID- 3324249 TI - Growth delay from a psychologic perspective. PMID- 3324250 TI - [Thrombocytopenia and thyroid disease. Presentation of 11 cases and review of the literature]. PMID- 3324251 TI - Lupus nephritis: classification, clinical features, and treatment. PMID- 3324252 TI - [In memoriam Alvaro Gomez Leal 1925-1987]. PMID- 3324253 TI - [Disorders of gestural expression in aphasics]. PMID- 3324254 TI - [Cardiovascular reactivity: from the isolated organ to the human being]. PMID- 3324255 TI - [Behavioral pattern of type A, stress and coronary disease. I. Short review of the literature]. PMID- 3324256 TI - The Wingate anaerobic test. An update on methodology, reliability and validity. PMID- 3324258 TI - Fundamentals of computerised data acquisition in the human performance laboratory. AB - Researchers of the future will depend upon computer technology to address questions that previously could not be answered using traditional methods of data acquisition. Recent advances in computer design and software availability have eliminated many of the limitations previously associated with computer use in the laboratory setting. Although computerisation facilitates the acquisition of laboratory data, identification of errors introduced into the measurement is often more difficult. The laboratory computer is only one component of an automated data acquisition system. A system designed to collect physiological data comprises several primary components, including: (a) sensing element; (b) signal amplification/conditioning circuits; (c) analogue display; (d) computer interface; (e) laboratory computer; and (f) acquisition software. The acquisition and conditioning of analogue signals is accomplished using traditional laboratory procedures familiar to the researcher. Converting this analogue signal into a digital format used by the computer, however, represents new techniques. Fundamentals of computerised data acquisition are discussed. An understanding of how an automated data acquisition system is configured and the techniques used to transform the values will assist the user in identifying sources of error introduced into the measurement. Additionally, familiarization with the methods of computerisation will provide insight into future applications of computer technology in the human performance laboratory. PMID- 3324259 TI - Heat tolerance, thermoregulation and ageing. AB - Older individuals, regardless of how one classifies 'old', are the most rapidly growing portion of the population. Statistics from heat waves and other morbidity mortality data strongly suggest that older persons are at greater risk of developing life-threatening manifestations of heat stress such as heat stroke. Most laboratory studies have found that ageing is associated with decreased heat tolerance and alterations in thermoregulatory effector responses. What is not so clear is the role of ageing per se in this decreased heat tolerance (as opposed to some concomitant functional decline, e.g. decreasing VO2max, which accompanies ageing across a population). Studies have shown decrements in resting heat tolerance and responses to thermal transients in older adults. With exercise in warm environments, most research has focused on the sweating response and it appears that whether or not sweating rate declines in the elderly is dependent upon the environment studied. In hot dry environments, older persons (of both sexes) consistently secrete sweat at a lower rate than their younger counterparts. However, as humidity of the environment increases, this difference tends to disappear. A key issue which deserves further attention is that of hydration in the elderly, both in terms of body water content and compartmentalisation, and of skin water content. Finally, ageing is often accompanied by other conditions (e.g. hypertension, diabetes, cardiovascular insufficiencies, long term therapeutic drug modalities) which further affect heat tolerance and thermoregulation. PMID- 3324260 TI - [The cancer patient and alternative medicine--a review]. PMID- 3324257 TI - Effects of ozone exposure at ambient air pollution episode levels on exercise performance. AB - Ozone is a principal component of photochemical air pollution endogenous to numerous metropolitan areas, which may induce irritant effects on the respiratory tract which impair pulmonary function, result in subjective symptoms of respiratory discomfort, including cough and shortness of breath, and can limit exercise performance. The effects of moderate ambient photochemical air pollution observed in a mobile laboratory have also been shown to be similar to those induced in laboratory chamber exposures to the same level of ozone alone. The metabolic demand of exercise increases minute ventilation (VE) and thus, the rate of ozone inhalation over that at rest. Potentially, exercise can also enhance the effects of ozone by: (a) reducing nasal passage absorption; (b) increasing the uniformity of ventilation throughout the lungs; and (c) replacing reacted ozone at a faster rate. However, results from 2-hour intermittent exercise and 1-hour continuous exercise exposures at the same total ventilation and ozone concentration have been shown to yield similar pulmonary function effects. It has been shown via significant variation in exercise intensity, and thus VE, that the simple product of ozone concentration, VE and exposure time (termed the ozone effective dose) predicts pulmonary function and exercise ventilatory pattern (induced rapid, shallow breathing) effects more precisely than ozone concentration alone. Better prediction of pulmonary function effects has been achieved via multiple regression analysis in which ozone concentration is given a greater weighting than VE and exposure time. Light intermittent exercise was first studied in 2-hour laboratory exposures to ozone at concentrations rarely seen in the ambient environment. In recent studies, heavy continuous exercise has been used in 1-hour exposures to ozone at levels routinely observed in photochemical episodes (less than or equal to 0.35 ppm). Statistically significant impairment of exercise performance has been observed at 0.18 ppm, a level reached for 1 hour, or more, on about 180 days per year in the Los Angeles basin. Responses of subpopulation groups, such as children, young adult females, older adults, and those with pre-existing pulmonary disease are not notably different from those of young adult males provided that the ozone effective dose is proportional to body size. Conversely, highly trained endurance athletes demonstrate significant responses at rather low ozone concentrations due to their ability to sustain very high VE over prolonged periods.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3324261 TI - [Trypanosa: enzyme and immunotherapy?]. PMID- 3324262 TI - [From the anatomic substrate to pathologic findings]. PMID- 3324263 TI - [Hypnosis, 100 years ago... review in the light of current knowledge]. PMID- 3324264 TI - [Immunobiology of the normal and tumor astrocyte]. AB - Immunobiology of the normal and tumoral astrocytes studies interactions between these cells and the immune system. Their antigenic characterization defines 3 classes of antigens: glial antigens, tumor associated antigens (neuroectodermal and gliomatous) and lymphoid differentiation antigens which can be modulated by gamma interferon and other cytokines. Glioma associated antibodies could be used for radiolocalization of tumours and for immunotherapy. The enhancement or induction of the Major Histocompatibility Complex antigen expression by interferon gamma could enhance tumour-antigen presentation by glioma cells to helper and cytotoxic T cells and thus activate the host's immune response. The presence of oncogenes and their products in glioma cells, mainly growth factor receptors, brings new potential therapies using oncogenes products as tumoral markers or as targets for monoclonal antibodies blocking their mitogenic activity. Normal and tumoral astrocytes produce lymphokines: interleukin 1, interleukin 3, prostaglandin E as well as a suppressor factor inhibiting interleukin 2 mediated effects and probably responsible for the suppression of glioma infiltrating T cells. The interaction of astrocytes with several humoral factors related to the immune system and their capacity to function as antigen presenting cells underline their importance for immune reactions within the central nervous system. PMID- 3324265 TI - [Controlled release levodopa-benserazide and changes in efficacy during treatment of Parkinson's disease]. AB - Twenty-five patients, 12 men and 13 women, 42 to 79 years (mean 62) were studied to determine possible interest of a controlled release preparation of L. dopa combined with benserazide. All patients were experiencing fluctuations in efficacy over the last 8 +/- 4 years. Their Parkinson disease was of long duration, (16 +/- 5 years), severe (Hoehn and Yahr's stages III to V) and treated with L. dopa for 12 +/- 4 years. Results were evaluated in the short, medium and long term. During the initial period the new treatment was substituted for previous therapy on a dose for dose basis. Long term (300 days) results showed that "end of dose" fluctuations had been improved in 40 p. 100 of cases without concomitant reduction in therapeutic effects, duration of "ON" periods progressing by 60%. The frequency of drug intake was unaltered but daily dosage could be increased by 30% without increasing severity of abnormal movements to a similar degree. The administration of this new presentation can be recommended, especially when frequent fluctuations compromise long term therapeutic effects. PMID- 3324266 TI - [Prescription of Theostat 300 as a single evening dose]. AB - Sixteen patients with asthma and/or chronic obstructive lung disease were treated for 8 days by scored tablets of sustained-release theophylline. Treatment was administered as a single evening dose per day, 2 hours after dinner, at a daily dosage of 10 mg/kg/day of theophylline. The theophylline curve remained in the theoretical therapeutic zone of 8 to 15 mcg/ml for about 14 hours; the clinical efficacy, evaluated on the basis of the improvement in the signs and symptoms, was satisfactory. The clinical acceptability was good apart from insomnia observed during the first 2 days of treatment. PMID- 3324267 TI - [Intrathoracic goiter. Retrospective study of 149 operated cases]. PMID- 3324268 TI - [Appropriate technology in the attendance of women]. PMID- 3324269 TI - [Polychemotherapy, combined or not to oral BCG, in the treatment of advanced breast cancer: final results of a controlled clinical trial]. PMID- 3324270 TI - [Breast feeding: a right of the mother and child]. PMID- 3324271 TI - [Non-hormonal treatment of postmenopausal osteoporosis]. AB - Non hormonal treatments for postmenopausal osteoporosis are curative and preventive treatments that do not call for sex hormones. Curative treatments aim to reduce the frequency of relapsing vertebral fractures and they mainly consist in sodium fluoride (50 mg/day) combined with Calcium (1 g element/day). Preventive treatments are intended to prevent the occurrence of vertebral fractures. They consist in calcium, physical exercise, vitamin D and calcitonin. Calcium and physical exercise are simple and inexpensive means which may be convenient for every woman, with no need for any preselection, and which can be combined together very well. They are however less effective than estrogen- progestogen combination. Vitamin D and its metabolites do not seem to be helpful for prevention of postmenopausal osteoporosis. Calcitonin is likely to offer good prospects for the future, because it has no major side effect and is able to restrain bone loss. Its use however will be dependent on a change in its mode of administration (intranasal), and a lowering of its cost (bacterial synthesis?). Lastly, a great effort has to be directed towards a thorough knowledge of osteoporosis risk factors, in order to carry out their elimination and the screening of high risk female patients. PMID- 3324272 TI - [Atypical hyperplasias of the endometrium]. AB - A review of the literature concerning atypical hyperplasias of the endometrium is presented. The new pathological classifications differentiate structural abnormalities from cellular abnormalities. For atypical hyperplasias with cellular abnormalities, similar classifications to that of Richard for the cervix have been proposed: Intra Endometrial Neoplasia (IEN) grades I to III. Evolution of these lesions toward endometrial adenocarcinoma must guide the treatment. In prospective studies, atypical hyperplasias with structural abnormalities evolve into adenocarcinoma in 1.6 to 22 per cent of the cases. In atypical hyperplasia with cellular abnormalities, they evolve into adenocarcinoma in 23 to 57 per cent of the cases, according to the authors. Total hysterectomy is the treatment which is the most suitable for atypical hyperplasias with cellular abnormalities. Continuous progestational medications before menopause and the same given intermittently before menopause, represent the possible medical treatments. PMID- 3324273 TI - [Clinical study of pivmecillinam hydrochloride in lower urinary tract infections in pregnant women. Apropos of 44 cases]. PMID- 3324274 TI - [Current status of chronic liver diseases]. PMID- 3324275 TI - [Gastrointestinal complications in patients with renal transplant]. PMID- 3324276 TI - [A brief history of endoscopy: chronicle of an achievement]. PMID- 3324277 TI - [Use of a portable pump for the treatment of sterility of hypothalamic origin]. PMID- 3324279 TI - Histopathological patterns of the liver involvement in visceral leishmaniasis. PMID- 3324278 TI - Coral snake venoms: mode of action and pathophysiology of experimental envenomation (1). PMID- 3324280 TI - [Characterization of Plasmodium falciparum strains of the State of Rondonia, Brazil, using microtests of sensitivity to antimalarials, enzyme typing and monoclonal antibodies]. PMID- 3324281 TI - Arhinia revisited. AB - Arhinia is a rare anomaly in which a total absence of the nose and parts of the olfactory system occurs. It is frequently associated with various multiple central nervous system (CNS) and somatic anomalies of different degrees of severity, with high mortality rate. Twelve cases that have been reported in the literature are analyzed according to multiple criteria. The anomalies that have been found to be associated with arhinia are: lack of olfactory bulbs and nerves, missing paranasal sinuses, high arched or cleft palate, various eye anomalies, low set ears - all in a very high incidence. Various degrees of CNS malformations have been found in part of the cases. Somatic anomalies have been reported in 50% of the cases. In two cases chromosome 9 anomalies have been reported. A classification is suggested in which arhinia is classified into arhinia (total absence of the nose and rhinencephalon) and partial arhinia (partial absence of the nose), each may or may not be associated with other malformations (facial, CNS and somatic). PMID- 3324282 TI - On the history of the Ermiro de Lima's approach to the ethmoid, sphenoid and frontal sinuses (preliminary report). PMID- 3324283 TI - Nasal squamous carcinoma in an undertaker--does formaldehyde play a role? PMID- 3324284 TI - 2,2,2-Trifluoroethanol-induced enteropathy in rats: chemically or bacterially mediated effects. AB - The lethal effects of the fluorinated ether anesthetic, fluroxene, in rats are a consequence of its metabolism, which is catalyzed by cytochrome P-450 to the toxic metabolite 2,2,2-trifluoroethanol (TFE). The anesthetic or TFE (0.21 g/kg) caused decreased white blood cell counts, necrosis of bone marrow and lymphocytes, and decreased small intestine dry weight and was associated with septicemia. To elucidate the mechanism of TFE toxicity in rats we undertook histopathologic, ultrastructural and bacteriologic studies. TFE produced severe edema of intestinal lamina propria and submucosae, dilatation of crypts, loss of surface epithelium, vacuolation and necrosis of intestinal epithelial cells, and infiltration of polymorphonuclear leukocytes into the edematous lamina propria. Intestinal epithelial villi lost their cellular tissue integrity. Coccobacillary organisms were numerous in the ulcerated intestine. Hemolytic E. coli were isolated from intestinal tissue at a two-log increase in concentration relative to controls. Hemograms from TFE-treated rats exhibited marked leukopenia and morphologic differences. The platelets lost their discoid shape, extended pseudopods, and centralizing granules. Hemoglobin precipitation as Heinz bodies and crystalloid structures was observed in TFE-treated rats. Together the data suggest that TFE-induced enteropathy was most probably due to E. coli precipitated from TFE-mediated alterations in the population of small intestinal microbes. The antibiotics erythromycin, active against gram-positive bacteria, and streptomycin, active against gram-negative bacteria, and the antiendotoxin, polymyxin B, were administered to rats prior to TFE in an effort to differentiate between these mechanisms by altering the intestinal bacteria populations. The results indicate that the TFE-induced small intestinal lesions are initiated by the direct focal necrotic effect of TFE or its metabolites on the small intestinal epithelium. The focal coagulation necrosis produced by TFE predisposes the animals to lethal enteritis and systemic bacteremia. PMID- 3324285 TI - Polyclonal B-cell activation and autoantibody formation during the course of mosquito-transmitted Plasmodium berghei infection in mice. AB - The time course of polyclonal B cell activation, as measured by titers of antibodies to DNP, FITC, and haemocyanin, as well as the time course of autoantibody formation, was followed in mice infected with Plasmodium berghei via Anopheles stephensi. IgM class antibodies to DNP, FITC, and haemocyanin appeared earlier than IgG class antibodies and persisted until death. Only IgM class anti DNP peaked, the others remained high until death. Although IgM class autoantibodies also appeared earlier than IgG class, they peaked sharply at days 14 to 15, as did antibodies to mouse RBC. Polyclonal B cell activation, as measured by spleen plaque-forming cells (PFC) using SRBC and TNP-SRBC in the direct test, peaked at day 13. This latter event could be correlated with the time course of hypergammaglobulinemia. PMID- 3324286 TI - Acute infectious diarrhea. AB - This review deals with the epidemiology of acute infectious diarrhea mainly with regard to third world countries. It also reports on advances in modern case management, oral rehydration, antibiotic therapy and problems of host resistance and transmission. PMID- 3324287 TI - Bilateral isolated internal iliac aneurysms presenting as pelvic tumours. AB - A case of a bilateral isolated internal iliac aneurysm is presented. A male patient of 74 years of age had a sudden attack of pain in the right lower abdomen. A superficial haematoma was the only finding at primary ultrasonography (US), while seven weeks later a control US visualised a pelvic expansion, but the aetiology was not recognised. The CT finding was pathognomonic for an aneurysm, the diagnosis being "bilateral iliac aneurysms". Digital subtraction angiography (DSA) defined the aneurysms as existing in the internal iliac arteries. PMID- 3324288 TI - The use of laser in neurosurgery. PMID- 3324289 TI - [Lymphocyte subpopulations in blood and articular fluid in rheumatoid polyarthritis]. PMID- 3324290 TI - [Value of protocols of alternating chemotherapy versus melphalan-prednisone during the induction phase of stage III myelomas. Critical review]. PMID- 3324291 TI - Pioneers of world and Romanian endocrinology. PMID- 3324292 TI - Chondrosarcoma of the orofacial region. Review of the literature and report of two cases. AB - Chondrosarcoma of the jaws arises from vestigial rests and is considered a rare entity, although it is more common than its benign counterpart. Occasionally it may be extremely difficult under the microscope to decide whether a case is benign or malignant. The treatment of choice is surgical with wide margins. In our review of the literature we found 169 cases of oro-facial chondrosarcoma including two from our Institution. There was a 2:1 male/female ratio and the maxilla was involved twice as frequently as the mandible. Over half of the cases were between 20 and 50 years old. PMID- 3324293 TI - Computerized laser Doppler interferometric scanning of the vibrating tympanic membrane. AB - The vibrational movements of the tympanic membrane (TM) of in vitro human specimens were studied by computerized laser Doppler interferometry. The versatility of the method for measuring the velocity of the vibrating TM was demonstrated by point measurements, horizontal sweeps, and three-dimensional scans of the entire TM. Single phases of the TM vibration were examined and plotted three-dimensionally. All information was stored digitally, making it possible to recreate the movements as in slow motion on the oscilloscope. The effect of coating the TM with a thin layer of magnesium oxide was studied. The repeatability of the method was demonstrated. TM vibrational patterns at different sound pressure levels and frequencies are displayed and discussed as also are the results of scanning the specimen in different positions. PMID- 3324294 TI - Endoscopic papillotomy. A clinical and experimental study. PMID- 3324295 TI - Loss of echoes from the gallbladder wall in diagnosis of fatty infiltration of the liver. AB - Ultrasonograms taken within 24 h before liver biopsy were evaluated retrospectively for fatty infiltration of the liver in 155 non-ascitic patients with liver diseases. Relatively high amplitude echoes of the liver as compared with the kidney were observed in all of 33 patients whose fatty infiltration of the liver occupied more than 10% of each lobule or pseudolobule irrespective of etiology. Among such patients, loss of echoes from the gallbladder wall was additionally found in 18 of 19 cases uncomplicated by hepatic fibrosis, but only in 3 of 14 cases with this complication. We conclude that fatty infiltration without fibrosis in the liver may be differentiated from that with fibrosis by ultrasonic examination. PMID- 3324296 TI - Gastric secretion kinetics in chronic renal failure. AB - A dose-response gastric secretion test was performed in 87 nondialyzed patients with chronic renal failure (CRF) and in 87 age- and sex-matched controls without renal disease. Twenty-six of the CRF patients were reexamined, 18 undergoing regular hemodialysis and 8 after successful transplantation. The gastric acidity, acid output, and volume output of the nondialyzed CRF subjects were decreased when compared with those of the controls or of patients in the posttransplant phase. This decrease was more marked with low than with high stimulant doses. The decrease in acid output was significantly greater than that in volume output. Moreover, when compared with the dialysis phase the nondialyzed patients had lowered gastric acidity and acid output, but no decrease in volume output was evident. The results indicate that there is an inhibition of gastric secretion in CRF. This inhibition is dependent on strength of stimulation and is abolished by active treatment of CRF, more clearly by transplantation than by maintenance dialysis. In addition, the inhibition is predominantly on the secretion of acid, the output of gastric juice being less affected. PMID- 3324297 TI - Pancreatic secretory response to intestinal stimulants: a review. AB - In humans and many laboratory animals, protein digestion products such as peptides and amino acids and fat digestion products such as fatty acids and monoglycerides are potent intestinal stimulants of pancreatic enzyme secretion. The pancreatic enzyme response to these intestinal stimulants is related to the perfused load (amount per unit time) rather than to concentration. Both neural and hormonal pathways mediate the enzyme response to these intestinal stimulants. Enteropancreatic, cholinergic, vago-vagal reflexes are probably the most important mediators of the enzyme response to low loads of amino acids and fatty acids; hormones, such as cholecystokinin, seem to be the major mediators of the response to high loads of amino acids and fatty acids. Under physiological conditions it is probably the interplay of neural and hormonal mechanisms which regulates the pancreatic response to these stimulants. Gastric acid is the major regulator of postprandial pancreatic bicarbonate secretion. Secretion released by HCl is probably the most important physiological hormonal mediator of postprandial pancreatic bicarbonate secretion; its effect being potentiated by extrinsic (vagal) and intrinsic (intrapancreatic) cholinergic nerves and release of other hormones, such as cholecystokinin. PMID- 3324298 TI - Papers dedicated to Professor Max Michel Forell on the occasion of his 70th birthday. PMID- 3324299 TI - Autoimmunity to pancreatic juice in Crohn's disease. Results of an autoantibody screening in patients with chronic inflammatory bowel disease. AB - The sera of 59 patients with Crohn's disease (CD) and of 46 patients with ulcerative colitis (UC) were tested for autoantibodies (Aab) by indirect immunofluorescence with modern histochemical techniques using 19 different human tissues as antigenic substrates. Control collectives consisted of 19 patients with coeliac disease and of 100 healthy subjects. It was possible to demonstrate a specific marker for CD: Aab against exocrine pancreas (Pab) were present in 39% of the CD sera (UC 4%, coeliac disease 0%, healthy controls 3%). High Pab titres were only detectable in CD sera (29%). The CD-related autoantigen was demonstrated to be a component of normal pancreatic juice. Pab in CD were fundamentally different from those sometimes occurring in chronic and acute pancreatitis. It is suggested that CD is caused by autoimmune reactions against a component of pancreatic juice. Pab in CD correspond to Aab against intestinal goblet cells (Gab), which occurred exclusively in UC (28%). Pab and Gab, but obviously none of the other Aab investigated in this study, are of diagnostic value in chronic inflammatory bowel disease. PMID- 3324300 TI - Indications for endoscopic neodymium-YAG laser treatment in the gastrointestinal tract. Twelve years' experience. AB - Application of clinical endoscopic Nd:YAG laser (lambda = 1.06 micron) therapy has been introduced in 1975. It is suitable to stop all kinds of gastrointestinal bleeding with a primary success rate of 94% (1144/1212). Compared to surgical results a reduction in mortality rate has been achieved. These results have been confirmed worldwide in routine clinical application and in controlled trials with selected patients. Potential bleeding lesions such as Osler haemangiomas and angiodysplasias can be sealed. Recanalization of inoperable obstructed oesophageal and gastric carcinoma by laser vaporization to relieve dysphagia and subsequently endoscopic iridium after loading irradiation show a medium survival time of 7.4 months. Preoperative recanalization of obstructed colorectal carcinoma to relieve ileus or subileus allows preoperative peroral bowel lavage and total colonoscopy to find synchronous cancers and polyps and to perform primary resections without intraoperative colon lavage. Sessile benign neoplastic polyps can be resected curatively by Nd:YAG laser vaporization. Recanalization of peptic stenosis and anastomotic scar stenosis can be performed. PMID- 3324301 TI - Improvement of endoscopic laser therapy in gastrointestinal ulcer bleeding by tissue infiltration. Basic experiments on the dog stomach in vivo. AB - The therapeutic effect of Nd-YAG laser coagulation in arterial ulcer bleeding seems to be improved by local epinephrine infiltration. The purpose of this animal study was to evaluate the safety of this new therapeutic modality. The effect of Nd-YAG laser on normal and on infiltrated gastric mucosa was compared in acute and chronic experiments on 14 beagle dogs. On exposed normal gastric wall, perforation time and power output were inversely correlated. The required energies are nearly constant at different power levels. After infiltration of sodium chloride as well as of epinephrine into the mucosa, however, perforation time increased four- to five-fold. Volumes of mucosa defects and of the coagulation zones were also lower after pretreatment by infiltration. The results encourage further clinical use of this new therapeutic approach. PMID- 3324302 TI - Intravesical ultrasound for staging bladder tumours. AB - Intravesical ultrasonic scanning was performed in 74 patients with 84 bladder tumours. Two tumours located, respectively, at the neck and in the dome of the bladder could not be visualized. In the other 82 the degree of infiltration was ultrasonically assessable. The tumours could be assigned to three categories: superficial, noninfiltrating (Ta to T1), infiltrating the bladder wall (T2 to T3a) and infiltrating extravesically (T3b to T4). The stage was correctly determined with intravesical ultrasound in 77 (94%) of the 82 tumours. The method is particularly valuable for differentiating between superficial, noninfiltrating and more advanced growths. PMID- 3324303 TI - Infection-induced urinary calculi and renal failure. AB - During 1974-1984 altogether 481 patients were treated for end-stage renal disease (ESRD). Eight patients, five women and three men, with chronic pyelonephritis as the primary cause of ESRD, had staghorn urinary calculi as a predisposing factor for renal failure. These eight patients were studied retrospectively concerning epidemiological and bacteriological aspects, the treatment of the stone disease, and the development of uraemia. Anatomical and metabolic abnormalities such as bladder outlet disturbances, primary hyperparathyroidism, phenacetin abuse or metabolic stone disease were found in six patients. The women had all been infected with Proteus mirabilis, whereas the men had been infected with various microorganisms. The average time taken for the development of ESRD, estimated from the first sign of renal impairment, was 7.4 +/- 2.9 (SD) years. Five patients had died before this study commenced. One of the patients still alive was on dialysis treatment. Two patients who were doing well without dialysis were stone free and had sterile urine after successful pyelolithotomy. It is concluded that the prevalence of infectious urinary calculi as a cause of uraemia in patients with ESRD is low. The time taken for uraemia to develop is short in these patients and they often have anatomical abnormalities. Proteus is commonly found in this group of patients. Patients with staghorn calculi, urinary tract infection and impairment of renal function are at risk of developing uraemia. PMID- 3324304 TI - Intestinal bacteria and rheumatic disease. AB - The striking clinical and pathological similarities between certain naturally occurring infectious diseases in animal species and those of some human rheumatic diseases, such as rheumatoid arthritis (RA), have stimulated the search for a microbial etiology of the latter syndrome. A long series of microbial species, including aerobic and anaerobic intestinal bacteria, mycoplasma and several viruses have been put into focus. Most often, however, an initially positive report has been followed by several reports denying an etiological role of the microbial species in focus. However, the concept of a microbial trigger in the etiology and symptomatology of RA is still a subject of intense debate. Recent results have indicated a reversed effect of gram-positive vs. gram-negative intestinal bacteria on adjuvant-induced arthritis in germfree rats and microbial peptidoglycans have been shown to play a major role in this experimental model. It has been shown that the intestinal flora may include bacteria containing antigenic determinant(s) cross-reacting with some markers within the HLA-system. The intestinal flora may also influence upon several digestive and absorptive functions and thereby acting upon parameters of importance in the development of rheumatic disease. PMID- 3324305 TI - The pathogenesis and consequence of non steroidal anti-inflammatory drug induced small intestinal inflammation in man. AB - Non steroidal anti-inflammatory drugs (NSAID's) have recently been shown to cause small intestinal inflammation in the majority of patients receiving these on a regular basis for more than one year. The development of inflammation is preceded by an NSAID effect to increase small intestinal permeability. Increased intestinal permeability is shown to be related to drug potency to inhibit cyclooxygenase and the effect is systemically mediated rather than a local irritant one. More recently, increased intestinal permeability due to NSAID's has been reduced by concomitant prostaglandin administration, showing that prostaglandins are essential for maintaining intestinal integrity in man. It is proposed that altered intestinal permeability allows the mucosa to be exposed to bacterial degradation products or other toxins and together with reduced chemotaxic response and altered neutrophil function due to NSAID's, this series of events leads to bacterial invasion of the mucosa which is evident by the techniques of 111Indium leucocyte scans and faecal collections. The consequence of such inflammation is that it may explain intestinal perforations and strictures which are occasionally seen in subjects on NSAID's. Most patients with NSAID-induced small intestinal inflammation may be bleeding from the intestine, loosing protein and some have ileal dysfunction. The small intestine may be a greater source of morbidity than the stomach, in patients receiving NSAID's. PMID- 3324306 TI - Immunoregulation in arthritis. A review on synovial immune reactions in RA and in some experimental animal models for arthritis. AB - Local synovial immune reactions have during recent years been characterized both in human arthritides, particularly in rheumatoid arthritis (RA), and in animal models for arthritis. Common characteristics of human RA on one hand and experimental adjuvant arthritis and collagen arthritis on the other hand, are induced expression of class II transplantation antigens on synovial cells close to the cartilage and presence of activated T lymphocytes in close proximity to these class II expressing cells. The present review aims to describe some implications of these and subsequent findings both concerning the analysis of the pathogenesis of RA and concerning some therapeutic implications derived from parallel studies on relevant features of the human RA and the respective animal models for arthritis. PMID- 3324307 TI - Clinical assessment of suspected damage from hand-held vibrating tools. AB - The case history is still the cornerstone in the clinical assessment of suspected vibration injury. Objective tests to verify the symptoms are needed for legal reasons in insurance cases and for research purposes. The minimum requirement of a test used to obtain objective signs of Raynaud's phenomenon is that patients with vibration-induced white finger be evaluated along with symptom-free, but vibration-exposed, subjects for reference. The measurement of systolic blood pressure in the finger after local finger and general body cooling is a test that has been evaluated in this way, as has restitution of finger temperature after local cooling and ischemia combined with general body heating. If neurological symptoms are present, electroneurographic examination is essential since carpal tunnel syndrome, a treatable condition, is common in vibration-exposed patients. Measurements of vibration and temperature thresholds are complementary examinations. The so-called vibrogram may be a method with which to obtain objective neurological signs of vibration injury, but the test needs further evaluation. Until more is known of the pathophysiological mechanisms behind the disease, the patient's description of his symptoms, combined with a detailed exposure history, will remain essential for a diagnosis of vibration injury- irrespective of the results of the tests used. PMID- 3324308 TI - Sensorineural stages of the hand-arm vibration syndrome. AB - Recent work has shown that the vascular signs and neurological symptoms commonly associated with exposure of the hand to vibration may develop independently. A classification for the neurological component of the hand-arm vibration syndrome has been developed for those symptoms dominated by sensory afferent involvement, based on the results of objective tests on 634 hands. The first symptomatic stage (1SN) consists essentially of episodic finger numbness with or without tingling, the second involves, in addition, reduced sensory perception (2SN), while the most severe stage (3SN) focuses on reduced tactile discrimination and/or manipulative dexterity. Consistent implementation of this classification by means of objective tests requires one, or more, precise, quantitative measure of peripheral somatosensory dysfunction, in addition to the traditional neurological tests (fine touch, pain, and temperature). Measurements of tactile function by means of esthesiometry or vibrotactile perception appear suited to this purpose. A procedure for staging individual hands may then be based on combining numerical scores assigned to the results of the traditional neurological tests and, additionally, esthesiometer and/or vibrotactile perception thresholds. PMID- 3324309 TI - Ergonomics and the effects of vibration in hand-intensive work. AB - Along with ergonomic factors, such as forceful and repeated exertion and certain postures, vibration has been cited as a factor of chronic nerve and tendon disorders such as carpal tunnel syndrome and tendinitis. The arguments for the contribution of vibration come from epidemiologic studies, clinical case analyses, and studies of short-term effects. It is well established that vibration stimulates muscle contraction, which is called the tonic vibration reflex. It is also known that vibration reduces tactility and that tactility affects the amount of force exerted to hold or manipulate a given object. For localized vibration exposure of the hand and arm to occur, the hand must grip a vibrating object. Vibration may increase the risk of chronic tendon and nerve disorders by increasing the force exerted in repetitive manual tasks. This close relationship between force and vibration, and difficulties in measuring force and vibration in manual work, makes it very difficult to determine their relative contributions in epidemiologic and clinical studies. PMID- 3324310 TI - Bone and joint pathology in workers using hand-held vibrating tools. An overview. AB - A literature evaluation was made with regard to the radiological documentation of bone and joint pathology in the hands and arms of workers using vibrating tools. There is evidence that work with pneumatic percussive tools (such as chipping hammers and scalers) may cause premature elbow and wrist osteoarthrosis, although of very low prevalence. This work-related disorder is not specific to vibration exposure. Instead, it is likely to result from the strong dynamic and static joint loading (often in extreme positions of the joint) and the repetitive hand arm movements (sometimes also repeated minor traumatization) typical for tool manipulation in any heavy labor. Exposure to low-frequency percussion may, however, play a particular etiologic role: damage to the joint cartilage by repeated shocks from the tool, additional articular load (and consequent strain) associated with a vibration-induced increase in the need for joint stabilization and higher gripping forces, the tonic vibration reflex (which increases muscle contraction), and a stronger grip induced when tactile sensibility is diminished by vibration. So far, no investigations have ventured into the great complexity of possible confounders and effect modifiers. -A constitutional susceptibility may be required to produce osteoarthrosis. -The allegation that hand-arm vibration exposure causes an excess prevalence of bone cysts, vacuoles, Kienbock's disease, or pseudarthrosis of the scaphoid has not been validly documented. -Exposure to vibration of higher frequencies (such as from rotating drills, grinders, and chain saws) does not seem to be associated with excess bone and joint pathology. -The observed large variation in the prevalence of skeletal disorders may be explained by biodynamic and ergonomic differences between various occupations. PMID- 3324311 TI - Centrally and locally mediated vasomotor activities in Raynaud's phenomenon. AB - A selective review on the attack of Raynaud's phenomenon in primary Raynaud's phenomenon and vibration-induced white finger is presented with special reference to the location of the primary vasospasm, the nature of the dominant pathophysiological mechanism, and the anatomic location of the abnormal link in this mechanism. It is suggested that the primary vasospasm is a total closure of the main digital arteries, that the arterial spasm is mainly mediated through an exaggerated central sympathetic reflex mechanism, and that the abnormal link in this reflex arch could be the smooth muscle cells of the digital arteries. Other anatomic locations of the abnormal link can however not be excluded as yet. PMID- 3324312 TI - Pathophysiological aspects of peripheral circulatory disorders in the vibration syndrome. AB - A review of current knowledge on the pathophysiological aspects of peripheral circulatory derangements in the hand-arm vibration syndrome is presented. Hemodynamic measurements indicate that the primary factor in vibration-induced white finger is an increase in peripheral resistance of finger circulation, present after local and general cooling. The reason for this increase is not known, but it is postulated that there is an excess affinity for the efferent receptors of vasoactive substances and that this affinity is potentiated during local cooling of the digits. PMID- 3324313 TI - Physiological methods used in Japan for the diagnosis of suspected hand-arm vibration syndrome. AB - In the pathogenesis of hand-arm vibration syndrome, vibration affects the peripheral system, especially the circulatory, nervous, and musculoskeletal systems. Medical questionnaires, physical examinations, and laboratory tests are used to diagnose the hand-arm vibration syndrome. The laboratory tests are satisfactory diagnostic aids for detecting slight disorders of the peripheral circulatory, nervous, and musculoskeletal systems. Peripheral circulatory function tests include skin temperature measured by a thermistor under specific temperature conditions, the nail compression test, and the cold provocation test (10-min immersion in cold water at 5 or 10 degrees C). To assess peripheral nervous function, tests for the pain and vibration senses are included. Peripheral musculoskeletal function tests consist of grip strength, pinch strength and tapping counts. These physiological tests are applied in worker screening twice a year. These tests have been authorized by the Ministry of Labour since 1973. Several criteria for the tests, although not authorized, are widely used. The diagnostic implication of each separate test may be low. Consequently, some laboratory tests should be evaluated, along with medical questionnaires and physical examinations, in the diagnosis of suspected hand-arm vibration syndrome. PMID- 3324314 TI - Finger thermometry in the assessment of subjects with vibration-induced white finger. AB - The measurement of finger skin temperature (FST) is one of the most commonly used methods for evaluating the response of the digital vessels to cold stimulation. In well-controlled experiments a significant correlation has been observed between FST and digital blood flow over a wide range of water temperatures. On the contrary, FST in air is considered an inadequate index of digital skin circulation since, at a given ambient temperature, FST depends not only on the rate of blood flow through the digit but also on environmental conditions. Despite these limitations, FST recording after a cooling procedure has been used in surveys of vibration-induced white finger (VWF), and a delayed finger rewarming time has been proposed as an indicator of digital vasospasm in workers with VWF. Finger skin thermometry can differentiate between VWF groups and healthy groups, but it is unsuitable for diagnosing Raynaud's phenomenon on an individual basis. The thermometric method has good specificity but its sensitivity is lower than that of plethysmographic techniques. FST after cold provocation may be considered a useful screening test in field studies, while more sensitive methods should be employed to confirm VWF symptoms in individuals objectively, especially for insurance compensation purposes. PMID- 3324315 TI - Pathogenic and clinical aspects of polyneuropathies, with reference to the hand arm vibration syndrome. AB - Along with attacks of white finger, symptoms suggesting peripheral sensorimotor neuropathy, ie, polyneuropathy or entrapment neuropathy, are very important in the hand-arm vibration syndrome. Peripheral neuropathies are probably associated with the occurrence of the syndrome because of a selection mechanism. Polyneuropathy may be a contributing factor in the development of entrapment neuropathies in the upper extremities. It has multiple pathogenic mechanisms and numerous causative factors. However, peripheral nerves can react to pathological stimuli in a limited number of ways. Wallerian degeneration, segmental demyelination, and axonal degeneration are the classical neuropathological types of peripheral neuropathies, of which the first two are possible direct consequences of vibration exposure. The clinical manifestations of polyneuropathy range from sensory to motor types, sometimes with autonomic involvement. Whenever polyneuropathy is encountered in the hand-arm vibration syndrome, its etiologic possibilities should be considered. Regardless of the variable criteria used by different authors, individual diagnosis of the syndrome is always a probability diagnosis, and adequate neurological differential diagnostics have to be employed. PMID- 3324316 TI - Clinical neurological methods in the diagnosis of the hand-arm vibration syndrome. AB - Methods for assessing neurological disturbances in the diagnosis of the hand-arm vibration syndrome are described. The clinical examination should comprise a careful history of symptoms and vibration exposure and a consideration of neurological signs known to be associated with vibration exposure. There is as yet no etiologic diagnostic method for vibration-induced neurological lesions. The best method is a relevant clinical examination as described, in combination with a quantitative assessment of sensory modalities (such as the vibration perception threshold) and an electroneuromyographic test. PMID- 3324317 TI - Peripheral neurological assessment methods for workers exposed to hand-arm vibration. An appraisal. AB - Peripheral neurological assessment methods for workers exposed to hand-arm vibration have included vibration perception and esthesiometric threshold testing, electroneurography, handgrip force, and manipulative dexterity. For epidemiologic investigations with the purpose of detecting vibration effects anticipated as moderate to large in size in occupational populations, these methods have demonstrated their usefulness. Concerning their value in the assessment of individual workers, there is little quantitative information, as there have been no studies which have conducted rigorous "gold standard" neurological evaluation with which the results of independently performed diagnostic tests can be compared. However, results from four papers which used depth-sense (or ridge) and two-point discrimination esthesiometry were available for an analysis of the sensitivity of these tests in the detection of Taylor Pelmear stages 2 and 3 of the hand-arm vibration syndrome. With specificity set at 90%, sensitivity ranged from 45 to 96% for depth-sense esthesiometry and from 19 to 75% for two-point discrimination. In addition, likelihood ratios were determined, as a measure of the capacity of the tests to alter pretest probability of disease. Because of their direct clinical interpretation and application, the use of likelihood ratios is suggested for future research on diagnostic methods used for vibration-exposed workers. PMID- 3324318 TI - New techniques for the diagnosis of carpal tunnel syndrome. AB - An overview is presented of the assessment of carpal tunnel syndrome (CTS) in manual workers, with emphasis on the distinction from other compression syndromes and from diffuse polyneuropathy. Clinical examinations, electrodiagnostic studies, the determination of vibration threshold, thermography, and, recently, computerized tomography have been used. This last-mentioned method has also been employed in a study indicating that a subgroup of the general population may possess a risk factor, small carpal canal, associated with the development of CTS. PMID- 3324319 TI - Assessment of concentration peaks in setting exposure limits for air contaminants at workplaces, with special emphasis on narcotic and irritative gases and vapors. AB - In various countries, concentration peaks of gaseous air contamination are assessed by a standard formula. Toxicologic data are not sufficient to warrant occupational short-term exposure limits for the majority of substances. In this article the literature on exposure to concentration peaks is reviewed, and the problem is analyzed from general toxicokinetic and physicochemical points of view. Several ways are suggested to achieve better standards. One straightforward and reasonably simple method is summarized in the following three points, which should be considered in the setting of occupational exposure limits: (i) For substances with fast or moderately fast action, only ceiling limits should be considered; (ii) when structure analogy is justified for narcotic and irritating gases, the correct way is to set the limits at the same thermodynamic activity (relative saturation) of the substances in question and not at the same concentration; (iii) for substances absorbed and eliminated slowly time-weighted exposure limits, combined with rules for excursions, or short-term exposure limits derived from such rules are appropriate, but the possible accumulation of large absolute quantities of the substances should be considered. This point is particularly important when the critical effect is narcosis or irritation, as the thermodynamic equipotency means that the effective concentration of water-soluble gases and vapors is higher than that of substances with low water solubility. PMID- 3324320 TI - Association between spontaneous abortion and ergonomic factors. A literature review of the epidemiologic evidence. AB - This article presents a literature review of seven epidemiologic studies which address the issue of spontaneous abortion and ergonomic factors. The following four ergonomic factors are analyzed: (i) shift work, (ii) piece work, (iii) posture, (iv) heavy lifting and physical effort. Among these factors, the last, heavy lifting and physical effort, is the only one that seems to be associated with an increased risk of spontaneous abortion. PMID- 3324321 TI - Waterborne paints. A review of their chemistry and toxicology and the results of determinations made during their use. AB - This work presents information on the composition of waterborne construction paints used in Denmark, data from determinations of chemicals evaporating from paints applied with a brush or roller, and the toxicology of these chemicals. Seven product types were selected to illustrate the composition of the paints. Measurements at two workplaces were used as models for the work environment during painting. Evaporating chemicals were collected on Tenax TA and analyzed with capillary column gas chromatography after thermal desorption. In smudging work, waterborne paints may result in skin irritation and/or sensitization when safety precautions are not taken. Irritation of the mucous membranes may be expected if airing is not sufficient. This irritation may lead to headache mediated by trigeminal nerve stimulation. No other health hazards (eg, brain damage) are expected. The available information indicates that waterborne paints are a clear improvement over traditional paints which use white spirit as the main solvent. PMID- 3324322 TI - Industrial problem solving with microbeam analysis. AB - The objective of this paper is to provide an overview of the microbeam analytical techniques and to help select the appropriate one to solve complex problems often arising in today's high-tech industries. Case histories are given to show how renowned analytical service laboratories and microbeam experts formulated their strategies to approach a real life problem, what type of conclusions were deduced from the data and, finally, how the problem was solved. PMID- 3324323 TI - An overview of platelet structural physiology. AB - Marion Barnhart and her colleagues used light, phase contrast and scanning electron microscopy to provide a clear picture of platelet surface changes developing in response to aggregating agents. This review, in honor of Marion and her work, has sought to expand the horizon provided through study of surface alterations by peeling back the membrane of the platelet to reveal the dynamic world within. A cytoskeleton consisting of a circumferential microtubule and submembrane actin filaments supports the discoid shape of the resting cell. Following exposure to aggregating agents in suspension, to foreign surfaces or denuded blood vessels and to fibrin strands during clot retraction, the state of assembly and organization of actin and location of the microtubule undergo dramatic alterations. There are differences in the cytoskeletal organization of platelets activated in suspension or on surfaces, during spreading on damaged blood vessels or in the process of clot retraction; yet, the similarities are far more impressive than the differences. The ability to assemble its cytoskeleton and adapt it to a variety of conditions requiring the exercise of contractile force makes the platelet a unique form of muscle cell. PMID- 3324324 TI - Megakaryocyte motility and platelet formation. AB - The mechanism of platelet formation is reviewed with special emphasis on the role of the cytoskeleton. The three major theories for platelet formation are by cytoplasmic budding, cytoplasmic dissolution or pseudopod formation. Most evidence indicates that platelets form as fragments of megakaryocyte pseudopodia. Pseudopodia formation is stimulated in vitro by thrombocytopenic rabbit plasma. It is inhibited by vincristine and altered by taxol. Cytochalasins cause pseudopodia to form in isolated megakaryocytes. Therefore, normal pseudopodia formation may depend on a combination of microfilament disorganization and microtubule elongation. PMID- 3324325 TI - Microvascular corrosion casting of the lung. A state-of-the-art review. AB - Corrosion casting and viewing of replicas with the scanning electron microscope is an excellent way to study the microvascular structure of the lung. This method can demonstrate aspects of the three-dimensional relationships, branching patterns, maximum diameters, arterio-venous connections, unusual sized and shaped capillaries, development and growth, neovascular structures and changes in development and disease better than any other means. Comparisons can be made in many experimental conditions and fundamental information obtained to answer physiologic questions. This paper reviews how the lung microvasculature has been studied by corrosion casting and scanning electron microscopy and indicates new areas where investigation might be pursued in humans and laboratory mammals. Although this technique has already greatly expanded our perception of the microcirculation, it should continue to be developed and become an even more valuable tool to study questions about the pulmonary vascular system. PMID- 3324326 TI - Scanning electron microscopy application in clinical research. AB - Our personal experience on the application of scanning electron microscopy in cardiology, gastroenterology and ophthalmology is reviewed. SEM has not yet significantly contributed to myocardium pathology. However, in the near future, SEM could be a reliable technique to complete the information available from other sources. As to atherosclerosis, SEM allowed us to improve our knowledge of the early stages of the disease; some pathological features, not always detected by conventional morphological examinations, can be documented. An important contribution to gastrointestinal pathology was made by SEM investigations both in the staging of some important diseases (i.e., coeliac disease, peptic ulcer, Crohn's disease, ulcerative colitis) and in the follow-up of mucosal changes during therapy. In the ophthalmological field, SEM provided three-dimensional new information to clinicians, who are familiar with the biomicroscopic images. Our experience in hematology is still limited. However, in the last few years SEM joined to immunocytochemistry allowed us to characterize cell populations in several blood diseases. Some procedures of particular interest in the management of human bioptic specimens are stressed in order to get to a complete correlative microscopy. We conclude that continuous and simultaneous correlations have to be carried out between SEM and other methods and instruments available for morphological investigation. PMID- 3324327 TI - The fine structure of the human placental villus as revealed by scanning electron microscopy. AB - Scanning electron microscopy of the placenta has a history of only twenty years. During that time, however, there have been dramatic advances in instrument technology coupled with the refinement of preparative techniques designed to reduce fixation artifacts to a minimum. As a result many of the early claims must be amended or suitably qualified, and this is one aim of the present review. Much new data on the internal structure of the placental villus is also presented. By means of the partial digestion technique it is now possible to describe the three dimensional configuration of the various components of the villous tree. This review will consider these sequentially, starting externally with the gross morphology of the villi and ending with replicas of the fetal vasculature produced by corrosion casting. PMID- 3324328 TI - Multiplane sectioning and scanning electron microscopy as a method for studying the three-dimensional structure of mature dental enamel. AB - A method is described where teeth are sectioned/ground along at least two planes, etched, and viewed at various angles in the SEM in order to study the three dimensional structure of enamel. This multiplane sectioning-scanning electron microscopy (MPS-SEM) method has been applied to the study of rat and human enamel. The method demonstrates in a direct way the complex three-dimensional structure of rat incisor enamel; the path of prisms and the distribution of interprismatic substance. The different appearance of alternate prism rows as seen in the longitudinal plane is seen to be due to prisms in alternate rows being inclined to different degrees in the transverse plane. In human enamel, the method reveals the three-dimensional nature of Retzius lines. In tangential planes cut at right angles to the prisms, Retzius lines are identified on the basis of an altered size, shape or etching pattern of prisms. Considerable variation in etching pattern within the same tangential plane was observed. Enamel tufts could be observed simultaneously in tangential and longitudinal planes, giving information about their three-dimensional extent and their relationship to Hunter-Schreger bands and to prisms and interprismatic substance. The main advantage of the method is that deduction of three-dimensional structure from the appearance of the structure in one plane is aided by the appearance of the structure in the adjoining plane. PMID- 3324329 TI - The root surface: an illustrated review of some scanning electron microscope studies. AB - This review paper highlights how the advent of a new type of surface microscopy in the late 1960s, scanning electron microscopy (SEM), was responsible for a fresh appraisal of the structure of the root surface. Details of the formation, resorption and repair of cementum, all surface phenomena, and the varied relationships and mineralization patterns of the two sets of fibres within cementum - the hall mark of the tissue - could be seen in a way and at a range of magnifications hitherto impossible. The major interpretational advances were made rapidly using secondary electron imaging of anorganic normal, exposed, carious and instrumented root surfaces. SEM made an important contribution to our knowledge of the composition of the microbial flora overlying the root surface by enabling the survey of plaque still kept intact on the whole tooth. It was possible to appreciate better the existence of distinct microenvironments within the plaque with their unique populations of interacting bacteria, and to see the location and prevalence of regions with special relationships between bacterial forms, such as "corn-cob" arrangements. Aspects of the structure of calculus, and its relationship to the cementum, were revealed in anorganic preparations. More recently, SEM cathodoluminescence and backscattered electron imaging have been applied to the study of normal and diseased root surfaces. The latter technique has proved particularly apt for detecting, in topography-free specimens, small variations and changes in the mineral content of roots and their acquired coatings. PMID- 3324330 TI - [Increased risk of bacterial colonization of intravenous catheters covered with transparent adhesive polyurethane bandages, compared to classical gauze bandages]. AB - While transparent polyurethane dressings are increasingly used for the care of intravenous catheters, concern has recently been expressed regarding their microbiological safety. We have therefore compared the rate of intravenous catheter bacterial colonization after randomly assigning intensive care patients to transparent polyurethane (n = 21) or dry gauze (n = 20) dressings. Polyvinyl chloride catheters were inserted and maintained by the nurses. No antiseptic or antibiotic ointment was used. The two groups of patients were similar regarding risk factors for catheter colonization. Colonization rate was 48% (10/21) among patients with transparent dressings versus 10% (2/20) among patients with dry gauze dressings (p = 0.008). Colonizing bacterial species were Staphylococcus epidermidis (11 strains) and S. aureus (1 strain). No catheter-related bacteremia was observed. These data suggest that the colonization rate of intravenous catheters is increased by the use of polyurethane dressings, possibly increasing the risk of septic phlebitis and bacteremia. PMID- 3324331 TI - [Endocarditis with unusual causative agents]. AB - In the period 1947-1985, 601 patients with infective endocarditis were seen at the University Hospital Zurich and the Kantonsspital Lucerne. Streptococci, enterococci and staphylococci were the predominant causative organisms in two thirds of all cases. In more than 25% of the patients blood cultures remained negative. In 6 patients endocarditis was caused by very rare organisms, viz. Coxiella burnetii (2 cases), Hemophilus parainfluenzae, Corynebacterium bovis (diphtheroids), Brucella melitensis and Aspergillus terreus. The clinical and microbiological characteristics of these cases are described and compared with the results in the literature. Diagnostic and therapeutic problems are discussed. Only with special awareness of the role of these unusual organisms in causing infective endocarditis, especially Q fever endocarditis with its notoriously atypical course, can the number of "culture negative" cases be diminished and the prognosis thereby improved. PMID- 3324332 TI - [Comparative in vivo studies of the marginal accuracy of the fit of Dicor and Cerestore crowns]. PMID- 3324333 TI - [Composite as an attachment cement? Initial clinical experiences in crown and bridge prosthetics]. PMID- 3324334 TI - [Toxicology of amalgams]. PMID- 3324335 TI - [Oral spirochetes and inflammatory periodontal diseases]. PMID- 3324336 TI - [Gene technology and veterinary medicine. II. Vaccines produced by genetic technics and analysis of highly variable DNA segments]. PMID- 3324337 TI - [Use of gentamycin in veterinary medicine: a review of the literature]. PMID- 3324338 TI - [Determination of normal values in the assessment of measurements and side differences in the ultrasonic study of the shoulder joint]. AB - Sonography of the rotator cuff with measurement of relevant soft tissue structures was performed in 120 persons without evidence of shoulder pathology. Although the extension of all structures varied markedly, no significant differences were found on comparing both sides. However, with regard to the variability of side differences, a limited side difference must be accepted as a normal finding. Sex, age and other body-related variables did not correlate well and were not useful in the assessment of the dimension of rotator cuff structures. PMID- 3324339 TI - [Initial experiences with angiodynography (color-coded duplex sonography) in the follow-up of vena cava filters]. AB - In vena cava filter thrombosis, plain films and real-time B-mode ultrasound are not reliably diagnostic. Angiodynography (colour-coded duplex ultrasound) was performed in 15 patients as an alternative to invasive methods. Despite of the relatively low depth of the used 5 MHz transducer, in 14 patients blood flow in the vena cava could be identified successfully. A nearly total occlusion of filter could be demonstrated in one case; in another patient partial thrombosis was not detected. Flow alterations around the filter were seen in the majority of cases. First experiences with the method were satisfying with regard to the particular problem. PMID- 3324340 TI - [Non-invasive diagnosis of the venous system of the leg in pregnancy]. AB - During pregnancy one should largely avoid invasive and radiological diagnostic methods. However, real-time sonography and venous occlusion plethysmography yield non-hazardous information on venous morphology and venous function. It became possible to demonstrate by means of these examination methods that the diameters of the veins are enlarged in pregnancy compared to the situation post partum. The difference in significant. Venous occlusion plethysmography points to a deterioration of venous function post partum, since the difference to the values in the third trimenon is not significant. Venous function measurement often pointed to the existence of an obstacle to flow during pregnancy, whereas sonographically a dilatation of the veins was revealed the existence of an obstacle to flow represented by the pregnant uterus. Hence, it appears meaningful to combine both investigation methods to confirm the occurrence of venous changes during pregnancy. PMID- 3324341 TI - [Sonographic imaging of normal adrenal glands in children and adolescents. An analysis of forms and reflex properties]. AB - 168 sonographic examinations were performed in 156 children and adolescents for evaluation of the adrenal glands. For the ventrolateral approach, real-time sonography was used resulting in 99% visualisation of the adrenal glands on the right and 91% on the left side. In prone position, static scanning provided acceptable imaging of the right adrenal gland in 85% and the left in 95% of examinations. The "success rate" of transverse scanning was relatively low (67%) as compared to longitudinal sections. The reflective property of the adrenal glands was compared with the reflex intensity pattern of the adjacent parenchyma of the normal kidney. In 71% of examinations no distinction could be made between the adrenal glands and the upper pole of the kidney on the basis of echointensity. In 29% the adrenal gland was echolucent in comparison to the kidney's parenchyma. In no instance was the echointensity of the normal adrenal gland greater. Although the shape of the adrenal glands was found to vary according to the angle and position of the transducer, the most common appearance in children of one year or older was that of a triangle, helmet or cap. This caplike appearance and the similarity in echointensity often make it difficult or even impossible to distinguish the adrenal glands from the upper pole of the kidney. It is therefore advisable to examine the adrenal glands in children from both laterally and dorsally to allow for optimum visualization. In contrast to some reports in adults, increased echointensity of the adrenal gland (adrenal cortex) in children should be considered as an abnormal finding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324342 TI - [Abdominal sonography in hereditary angioneurotic edema. A contribution to the early diagnosis of a disease of interdisciplinary significance]. AB - Hereditary angioneurotic oedema is a rare complement-related disorder (C1 esterase-inhibitor deficiency) characterised by recurrent episodic swelling of the limbs, face, gastrointestinal tract, or airways. The mortality rate of the unrecognised disorder is 30 per cent, mainly due to airway obstruction. Two female patients (aged 29 and 61 years) with proven disease were studied by ultrasonography while they suffered from acute abdominal pain: Ultrasound imaging showed a diffuse oedematous but compressible gut wall with reduced bowel motility, distended bowel loops with intraluminal fluid accumulation and free fluid in the peritoneal cavity. The ultrasonographic feature was different from that of other gastrointestinal diseases. In combination with the patient's history, the clinical pattern and the normal routine laboratory findings, abdominal ultrasonography is a suitable tool for early diagnosis of a potentially life-threatening disorder. PMID- 3324344 TI - [Polytrauma--treatment by the staged diagnostic and therapeutic plan]. PMID- 3324343 TI - [Primary sonographic diagnosis of pancreatic duct calculi: the non-uniform aspect]. AB - Four cases of sonographically visualised intraductal pancreatic calculi are reported. In three of these cases the calculi had been caused by chronic pancreatitis, and in one case by carcinoma of the head of the pancreas. The calculi did not present a uniform sonographic pattern, especially as regards echogenicity. A dorsal echo extinction was observed in three cases only. The non uniform sonographic aspect of intraductal pancreatic calculi can probably be ascribed to differences in the lime content. PMID- 3324345 TI - [Principles of surgical therapy of bone tumors with special reference to localization in the pelvis and lower extremity]. PMID- 3324346 TI - [Morphologic correlates of sonographic images of shoulder joints in living probands and autopsy samples]. PMID- 3324347 TI - The intrahepatic biliary epithelium: an area of growing interest in hepatology. PMID- 3324348 TI - New concepts in biliary cirrhosis. PMID- 3324349 TI - Dysmotility disturbances of the biliary tract: classification, diagnosis, and treatment. PMID- 3324350 TI - Direct contact dissolution of gallstones. PMID- 3324351 TI - Fragmentation of gallstones by extracorporeal shock waves. PMID- 3324352 TI - Recent advances in the management of primary sclerosing cholangitis. PMID- 3324353 TI - Pharmacokinetics of NSAID with special reference to the elderly. PMID- 3324354 TI - Quantitation of urinary red blood cells by phase-contrast microscopy: its relationship to severity of glomerular damage. PMID- 3324355 TI - The use of naftifine (Exoderil) cream in the treatment of dermatophytosis. PMID- 3324356 TI - Health insurance coverage of the working poor. AB - This study examines the working poor, and their pattern of health insurance coverage. The data indicate that in 1977 almost 22% of the working poor lack health insurance throughout the year. Moreover, children of the working poor were almost twice as likely as children of the poor nonemployed to be without coverage. The implications of the Omnibus Budget Reconciliation Act of 1981 (OBRA) which restricted the working poor's eligibility for Medicaid are discussed. It is argued that being employed, in itself, does not guarantee poor people access to medical care and may, in fact, serve to restrict it. PMID- 3324357 TI - Genital chlamydial infection: a role for social scientists. AB - Potential sociomedical research contributions to the understanding of genital chlamydial infections are outlined in a six-part sociomedical 'checklist'. Sociomedical research focuses on human behavior and its social, economic, cultural, and psychological determinants. Thus, the author urges sociomedical researchers--primarily medical sociologists, medical anthropologists, social psychologists, and public health economists--to explore the cultural, socioeconomic, and behavioral factors contributing to the current 'epidemic' of genital chlamydial infection, a sexually transmitted disease (STD) that is found worldwide and has now supplanted gonorrhea as the most common STD in the industrialized nations. Control of this STD is particularly important because of its grave consequences for women's and maternal/child health; these include ectopic pregnancy, infertility, and neonatal morbidity. Before effective prevention and control programs can be realized, however, beliefs and behaviors surrounding such areas as sexuality, fertility, contraception, STDs, hygiene, and health care must be discerned for widely based populations in both industrialized and nonindustrialized nations. PMID- 3324358 TI - Historical review of the changing pattern of infant feeding in developing countries: the case of Malaysia, the Caribbean, Nigeria and Zaire. AB - Prolonged lactation and early supplementation have been traditional practices among low-income mothers in Malaysia, the Caribbean, Nigeria and Zaire. Early supplementation is still the norm but there have been some substantial changes in the types of supplement offered. Thus, except in Zaire, there is now widespread use of processed milks as supplements for very young infants. The use of processed milks began in the 1920s in Malaysia and the Caribbean, but not until the 1960s in Nigeria. Processed milks are, as yet, rarely used in Zaire. The use of processed milks has not, however, led to the abandonment of traditional paps. The latter are still given as supplements to young infants in Nigeria and to older infants in Malaysia and the Caribbean. Breast-feeding duration has declined in Malaysia and the Caribbean although initiation is almost universal. In Nigeria and Zaire most low-income mothers continue to breast-feed for at least 12 months. The changes in the types of supplements used and in breast-feeding duration are analogous to the changes observed in industrialised countries from the mid-19th century, and many of the associated factors are similar: urbanisation; female participation in the labour force; increased availability of processed milks and their promotion both by companies and the health sector; and the regimentation of breast-feeding. This review highlights the negative role played by the health sector in the past, and discusses its future role in promoting and supporting breast-feeding. PMID- 3324359 TI - Predicting low birthweight and complicated labor in urban black women: a biopsychosocial perspective. AB - This study explored demographic, biomedical and psychosocial factors as predictors of two adverse pregnancy outcomes: intrapartum complications and low birthweight, in 140 urban black pregnant women. The intrapartum complication rate was 18%. A four factor equation (low family functioning, advanced maternal age, working during pregnancy, and short stature) predicted intrapartum complications (80% sensitivity, 67% specificity and 35% positive predictive value). The low birthweight rate was 14%. Four factors (low family functioning, stressful events, Quetelet's Index, and cigarette smoking) predicted low birthweight (65% sensitivity, 84% specificity and 42% positive predictive value). Family functioning, alone, predicted low birthweight with 65% sensitivity, 64% specificity and 31% positive predictive value. Family functioning, was the only predictor for both outcomes. Family functioning and other psychosocial risk factors may potentially improve identification of high risk pregnant urban black women. PMID- 3324360 TI - [Archaic concepts from the 19th century. The diseases which should not be cured]. PMID- 3324361 TI - Dengue haemorrhagic fever in Malaysia: a review. AB - The historical background, epidemiology and changing pattern of clinical disease as seen in Malaysia is reviewed. The preliminary results of the longitudinal study of epidemiology of dengue in Malaysia is also presented. Studies led by Rudnick et al. over some 18 years have established that the disease is endemically transmitted by both Aedes aegypti and Aedes albopictus causing illnesses ranging from mild febrile episodes through classical dengue fever, dengue haemorrhagic fever and the dengue shock syndrome. The first epidemic occurred in 1962 in Penang, and the second major epidemic in 1974 in Selangor. From then on epidemics seem to occur every 4 years, i.e. 1978, and then in 1982. With increasing number of cases being seen from the end of 1985 and in 1986, and with the increasing numbers of positive virus isolates, another epidemic may occur this year. Though in the early years, mainly children were affected, recently more cases are being seen in 16-30 years age group. There is also a changing pattern in the clinical presentation of the cases. The clinician has to be aware of the various modes of presentation of this sinister disease. A high index of suspicion is needed for early diagnosis, as management is mainly symptomatic and there is no specific drug as yet to combat the shock and bleeding manifestations. PMID- 3324362 TI - Immunological aspects of dengue haemorrhagic fever: studies in Thailand. PMID- 3324363 TI - Antibodies to dengue viral polypeptides. I. Sensitivity and specificity of the viral-antigen-strips/enzymeimmunoassay (VAS/EIA). AB - The authors applied polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE), western blot, and enzymeimmunoassay (EIA) for the detection of antibodies toward individual dengue viral proteins or polypeptides. SDS-PAGE procedure as described by Laemmli et al., was applied and modified. The results can be observed by visualization. The scores, from 0 to 4, can be assigned by comparing the intensity of the color development. Besides being sensitive and rapid, this technique yields information of the polypeptides or molecular level. An increasing of intensities of positive reactions indicated rising in antibodies titers and all serotypes of dengue viruses (from type 1 to type 4) can be tested together allowing reliable comparison among serotypes. With hyperimmune human sera, at least 13 polypeptides reacted with sera while negative non-immune subject showed no reaction. It is highly possible to use this technique as a rapid quantitative and for qualitative analysis of antibodies to individual viral proteins as well. PMID- 3324364 TI - The role of steroids in dengue shock syndrome. PMID- 3324365 TI - Sixth D. J. du Plessis lecture. Research in the field of gastric and duodenal ulceration. PMID- 3324366 TI - [Prevalence and risk factors of peripheral arterial occlusive diseases and coronary heart disease]. PMID- 3324367 TI - Experimental mercury-induced glomerulonephritis. PMID- 3324368 TI - IgA nephropathy. PMID- 3324369 TI - Therapy of idiopathic membranous nephropathy. PMID- 3324371 TI - [Clinical aspects of combined pharmacotherapy in diseases of the internal organs]. PMID- 3324370 TI - Treatment with cyclosporin of patients with idiopathic nephrotic syndrome. PMID- 3324372 TI - [Determination of the size of the myocardial infarct by electrocardiographic methods]. PMID- 3324373 TI - [Minimal change glomerulonephritis]. PMID- 3324374 TI - [Evaluation of the clinical criteria of chronic pyelonephritis]. PMID- 3324375 TI - [Eliazar Markovich Gel'shtein (on the 90th anniversary of his birth)]. PMID- 3324376 TI - [Fibrinogen and fibrin degradation products in the blood of acute myocardial infarct patients at the hospital rehabilitation stage]. AB - An enzyme immunoassay was used for a study of the time course of the content of fibrinogen degradation products (FDP) and free hemoglobin (fHg) in the blood of patients with acute myocardial infarction (AMI) during uncomplicated hospital rehabilitation. A considerable increase in the levels of FDP in the blood serum and fHg in the blood plasma of the AMI patients were noted. These levels were particularly high on the 6-12th day of rehabilitation with further fluctuations on the 22-24th day from the beginning of disease resulting from an increase of the patients' motor activity during rehabilitation which might cause the depletion of endothelial reserves of fibrinolysis activators and an increase in thrombinemia, however changes in the content of FDP and fHg in the blood were more likely associated with DIC-syndrome inherent fluctuations in the system of hemostasis. The content of FDP and fHg in the blood of AMI patients was recommended to be used as a marker of DIC-syndrome and assessment of corrective therapy. PMID- 3324377 TI - [Endoscopic arrest and prevention of recurrences in acute gastroduodenal hemorrhages]. AB - A single use of endoscopic arrest of gastroduodenal hemorrhages slightly improves therapeutic results for this group of patients but does not prevent hemorrhagic recurrence deteriorating sharply prognosis in patients with acute gastroduodenal hemorrhages. Daily endoscopic control with adhesive applications for 5-10 days will make it possible to reduce the number of repeated hemorrhages and to improve the results of therapy of patients with gastroduodenal hemorrhages. However, daily endoscopic inspections are not always possible and economically appropriate. Therefore, the author proposes a search for new methods of endoscopic arrest and prevention of recurrences of acute gastroduodenal hemorrhages. PMID- 3324378 TI - Teflon strip pneumostasis for excision of giant emphysematous bullae. AB - Excision of giant emphysematous bullae commonly results in a persistent air leak that requires prolonged intercostal drainage and delays recovery. To minimise this we have used Teflon (polytetrafluoroethylene) strips to buttress the suture line and secure pneumostasis. During 1976-84 eight bullae were excised in seven patients. One patient had bilateral staged thoracotomies. All chest drains were removed within eight days (mean 4.5 days) and no patient developed pulmonary complications. At long term follow up (1-9 years, mean 5.5 years) no complications attributable to the Teflon felt have been identified. PMID- 3324379 TI - Human immunodeficiency virus infection: screen, be clean, or both? PMID- 3324380 TI - Baboon models of acute arterial thrombosis. AB - In conclusion, we believe that the baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, the effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in different model systems. For example, the AV vascular graft model is efficient, cost effective and well adapted to study interventions for acute arterial thrombosis. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo. PMID- 3324381 TI - On the mechanism of thrombolytic action of thromboxane synthetase inhibitors. AB - Using our in vivo model for studying drugs which prevent deposition of thrombi or dissipate thrombi formed in extra-corporeal circulation over a collagen strip superfused with arterial blood of anaesthetized and heparinized cats, we have found that dazoxiben--a thromboxane synthetase inhibitor--possesses not only antithrombotic but also thrombolytic potency in vivo (ED50 = 3.8 mg/kg i.v.). The thrombolytic potency of dazoxiben was antagonized by aspirin at a dose of 50 mg/kg i.v. Moreover, dazoxiben stimulated the generation of prostacyclin in isolated rat aortic slices incubated in platelet rich plasma, but not in platelet poor plasma. It is suggested that the thrombolytic potency of thromboxane synthetase inhibitors after their systemic administration is associated with the release of prostacyclin and/or prostacyclin-stable metabolites by the vascular endothelium owing to feeding of prostacyclin synthetase with prostaglandin endoperoxides accumulated in platelets following the inhibition of thromboxane synthetase. PMID- 3324382 TI - Hemostatic disturbances associated with implantation of an artificial heart. AB - Coagulation and platelet parameters have been assessed following implantation of a Jarvik 7 artificial heart. Initially an ongoing intravascular coagulation could not be overcome with heparin and coumarin. The in vivo formation of thromboxane A2 (as monitored by measurement of the major urinary metabolite) was increased 3 4 fold. Administration of aspirin every second to third day reduced the thromboxane formation dramatically. In parallel to this, the intravascular coagulation subsided, the demand for heparin decreased considerably and the clinical condition of the patient improved. These events provide evidence for a direct link between thromboxane formation and the coagulation cascade. The thromboxane formation was insufficiently suppressed around the 110th postoperative day. Two weeks later the patient suffered a cerebral embolus, followed by a bleeding in the embolized area. This case illustrates the applicability of antiplatelet treatment when the need for efficient antithrombotic treatment is especially pronounced. Aspirin, however, is not the ideal drug for this purpose. PMID- 3324383 TI - Ethanol stimulates prostacyclin biosynthesis by human neutrophils and potentiates anti-platelet aggregatory effects of prostacyclin. AB - Previous reports on the direct effects of ethanol on human platelet aggregation function have been inconsistent. Ethanol ingestion produces vasodilation and raises intracellular cyclic AMP concentrations, effects similar to those of prostacyclin. We, therefore, hypothesized that ethanol may influence biosynthesis and/or bioactivity of prostacyclin. In our experiments, ethanol in concentrations up to 400 mg% had no consistent inhibitory effect on platelet aggregation in response to epinephrine, ADP, or combination of subthreshold concentrations of epinephrine plus ADP. However, ethanol in concentrations as low as 10 mg% potentiated the platelet aggregation inhibitory effects of prostacyclin. In addition, ethanol (20 mg%) decreased formation of thromboxane A2 in whole blood by 41% and stimulated formation of prostacyclin by 160% (both P less than 0.01). Additional studies using isolated human cells demonstrated synthesis of prostacyclin by neutrophils in the presence of platelets, and this neutrophil prostacyclin formation was enhanced in the presence of ethanol. These effects of alcohol in concentrations achieved after moderate intake may relate to the hemodynamic, biochemical, and cardioprotective effects of ethanol. PMID- 3324384 TI - [Obstructive sleep apnea syndromes. Treatment with nasal continuous positive pressure]. PMID- 3324385 TI - [Tissue adhesives versus conventional skin closure]. PMID- 3324386 TI - [A physician in the Finnmark. Niels Christopher Suhr (1768-1816)]. PMID- 3324387 TI - [Epileptic hallucinations in 1900--poetry or truth?]. PMID- 3324388 TI - [Physicians as murderers]. PMID- 3324390 TI - [Doppler examination of blood flow velocity waveforms in the umbilical artery]. PMID- 3324389 TI - [Amaurosis fugax. Causes, symptomatology, prognosis and therapy]. PMID- 3324392 TI - Summary review of the health effects associated with phenol. AB - Phenol, a monohydroxy derivative of benzene, occurs naturally in animal waste and by decomposition of organic wastes. It is also produced by man, originally by fractional distillation of coal tar, but more recently by cumene hydroperoxidation and toluene oxidation. As a result of large production volume and natural sources, occupational and environmental exposure to phenol is likely. Phenol poisoning can occur by skin absorption, vapor inhalation, or ingestion, and, regardless of route of exposure, can result in detrimental health effects. Acute toxicity has been observed in man and experimental animals, resulting in muscle weakness, convulsions, and coma. In addition, studies have shown that although teratogenic effects have not been associated with exposure to phenol by either inhalation or oral route, high doses of phenol are fetotoxic. This paper addresses these studies and others in an attempt to determine if human health is at risk to those levels of phenol present in the environment and workplace. However, because data are limited, further research is necessary to analyze the mutagenic and carcinogenic potential of this chemical. PMID- 3324391 TI - Correspondence of results from hepatocyte studies with in vivo response. AB - Isolated hepatocyte systems are being examined in our laboratory for a number of applications, including alternatives to animal testing. This report summarizes findings from studies with chlorinated aliphatics, acetaminophen, nitrotoluenes, and cyanide and its antidotes that relate to in vivo toxicity and validation of these systems for cytotoxicity screening. PMID- 3324393 TI - A simple technique to increase depth of focus in low power photomicrography through the compound microscope. PMID- 3324394 TI - Modification of multiwell culture dishes to house tissue sections during processing. PMID- 3324395 TI - [Use of chromosomal analysis in expert testimony with regard to disputed paternity]. PMID- 3324396 TI - [Ultrasonic express paraffin handling of histological specimens]. PMID- 3324397 TI - Fetal liver transplantation. Developments in hematology and immunology. PMID- 3324398 TI - Synopsis and prospectives on fetal liver transplantation. AB - Over 300 individuals have received fetal liver transplants for a spectrum of disorders including immunodeficiencies, aplastic anemia, leukemia and genetic disorders. In some instances, the objective has been to reconstitute the immune system from fetal liver-derived lymphoid stem cells. In aplastic anemia and leukemia two distinct approaches have been used: engraftment of fetal liver derived hematopoietic stem cells or attempts to stimulate recovery of autologous hematopoiesis via factors produced by fetal liver. In genetic disorders, partial engraftment of fetal liver-derived hematopoietic and hepatic cells has been investigated. This report critically reviews data presented at a symposium on fetal liver transplantation in New-Delhi, 1-5 February 1986. PMID- 3324399 TI - Bone marrow recovery following fetal liver infusion (FLI) in aplastic anaemia: morphological studies. AB - Twenty-two of 35 patients with aplastic anaemia who received fetal liver infusion (FLI), responded to this treatment. Detailed review of bone marrow aspirates and biopsies was available in 17. There was a good correlation between clinical improvement and blood counts. The bone marrow cellularity increased to 48 percent in about 18 weeks with repopulation by both erythroid and myeloid cells. The erythroid response was predominant and the earliest to occur (1.5-61 weeks); it lasted for 7.5-100 weeks. Marked dyserythropoiesis was observed. Myeloid response occurred simultaneously in 45 percent of the responders; in the others it was delayed by 1.5 to 4 weeks. Significant dysmyelopoiesis with shift to the left, unrelated to infection, was seen 1.5 to 9.5 weeks after FLI lasting for 9-26 weeks in most cases. Megakaryocytic response either did not occur or was delayed, less marked and often transient. PMID- 3324400 TI - Fetal liver infusion in acute myelogenous leukaemia. AB - Forty-five patients with acute myelogenous leukaemia (AML) received induction chemotherapy with either a conventional dose of cytarabine and daunorubicin (27 patients) or a low dose of cytarabine (18 patients). Maintenance chemotherapy was given to all responders. In 14 of 39 evaluable patients, infusion of fetal liver cells from 10-24 weeks old foetuses was given following induction as well as maintenance therapy. Six of 14 patients (43%) achieved a complete remission; 2 showed evidence of transient engraftment documented by analysis of sex chromosomes and RBC antigens (1 patient each). Fetal liver infusion within 6 days of completing induction chemotherapy appeared more effective than when given later. Five of 25 patients (20%) who did not receive fetal liver infusion achieved a complete remission. The present work suggests that fetal liver infusion given following induction chemotherapy may increase the remission rate in AML either by temporary engraftment or by accelerating the rate of haematological recovery. PMID- 3324401 TI - Sustained recovery of hematopoiesis and immunity following transplantation of fetal liver cells in dogs. AB - We studied the ability of fetal liver cells to reconstitute hematopoiesis and immunity in lethally irradiated dogs. Engraftment and sustained lymphoid and hematopoietic recovery was achieved when the recipients received a preparative regime of high-dose total body irradiation (TBI) alone followed by transplantation of DLA-identical fetal liver. The combination of high-dose TBI and cyclosporine allowed engraftment in DLA-mismatched fetal liver transplants. Typical features of graft-versus-host disease (GvHD) did not occur although autoimmune-like syndromes (myasthenia gravis, immune thrombocytopenia) were observed in some recipients. Hematopoietic recovery was rapid and complete. Recovery of T- and B-lymphocyte function was comparatively delayed, but sufficient to prevent opportunistic infections after the initial 3 months post transplant. These data indicate that cells from a single fetal liver can reconstitute hematopoiesis and immunity in DLA-mismatched recipients and suggest that human fetal liver cell transplantation may be an effective source of stem cells for patients who lack an HLA-identical donor for bone marrow transplantation. PMID- 3324402 TI - HLA status following fetal liver transplantation in aplastic anaemia and acute myeloid leukaemia. AB - Fetal liver infusion (FLI) was tried as an alternate mode of therapy in 40 patients with aplastic anaemia and in 16 patients with acute myeloid leukaemia. The fetal HLA typing carried out on spleen and thymus cells revealed that, while it was more difficult to HLA type the thymus than the spleen cells, 'full house' antigens could be determined only in fetuses of 18 weeks or older. No special effort was made to transfuse HLA- matched or partially matched donor cells into the recipient. The recipients were HLA typed at varying time intervals following FLI in an attempt to document a possible chimerism. None of the patients revealed a 'shift' in their HLA antigen profile and there was no evidence of any donor cell engraftment. No relationship between the HLA match of donor and recipient, and the general condition, the prognosis or the total survival of the patient was evidenced. These data indicate that, even though fetal liver cells express HLA antigens, these cells are functionally incompetent to cause an apparent graft versus-host disease in the host. PMID- 3324403 TI - A comparison between ALG and bone marrow transplantation in treatment of severe aplastic anemia. AB - One hundred patients with severe aplastic anemia were treated and evaluated in a prospective study at our hospital between January 1976 and October 1983. 28 patients had a HLA-identical sibling donor and were treated with bone marrow transplantation. 72 patients without a HLA-identical sibling donor were given antilymphocyte globulin followed by oral low dose androgen therapy. One and a half years to nine years after treatment 13 patients (46%) survive in the transplant group and 53 patients (74%) survive in the second group. All except one in the second group have self-sustaining hematopoiesis without need for transfusions. There is one major difference between the two therapies. Marrow transplantation restores bone marrow function completely and no late hematological complications have been seen in this group. The majority of patients treated with antilymphocyte globulin in contrast have residual abnormalities of hemopoiesis: macrocytosis, mild granulocytopenia and mild thrombocytopenia. Relapse (11 of 72 patients) and clonal hematological disorders, such as paroxysmal nocturnal hemoglobinuria (4 patients) and leukemia (one patient) can occur years after complete bone marrow reconstitution with antilymphocyte globulin. These late disorders are of concern. In spite of this we conclude that antilymphocyte globulin treatment is an effective therapy with low early mortality and morbidity and a high chance for a long sustained remission. Results are better or at least equivalent to bone marrow transplantation and patients with donors should be given the option of transplantation or antilymphocyte globulin. PMID- 3324404 TI - Development of the immune system in human fetal liver. AB - Fetal liver is a major site of development of the human immune system. Pre-B and B-lymphocytes are present in the human fetal liver at 12 weeks in a random distribution and increase with gestation. Most fetal liver cells are pre-B but mature B-cells are also present. Functional assays and transplantation experiments indicate that these B-cells are functional and can transfer immunologic memory, albeit imperfectly, in fetal liver reconstituted recipients. T-cell development, in contrast, occurs predominantly in the thymus. Progenitors of T-cells are present in fetal liver and can restore T-cell immunity in irradiated recipients. Human fetal liver contains 1-2% mature T-cells; functional assays are likewise negative. NK cells have been detected in human fetal liver at low frequency. Fetal liver also contains non-T, non-B cells capable of suppressing the development of alloantigen reactive T-cells; these have been termed veto cells. In summary, human fetal liver contains progenitors of several types of lymphoid cells and is an important site of immune development. It also may play a role in the induction of self tolerance during maturation of the immune system. These features of fetal liver may have important implications for the success of fetal liver transplantation in man. PMID- 3324405 TI - Fetal tissue transplantation, bone marrow transplantation and prospective gene therapy in severe immunodeficiencies and enzyme deficiencies. AB - The successful development of fetal tissue transplantation has resulted in therapeutical solutions for patients with a variety of diseases. Fetal liver transplants as well as bone marrow transplants, can completely cure patients with severe combined immunodeficiency disease. These transplants can also be applied to treat other types of immunodeficiency, hemopathies, and inborn errors of metabolism, in association with immunosuppressive therapy. Despite complete HLA incompatibility between transplanted stem cells and host cells, functional activities of donor-derived T-lymphocytes are not restricted. In severe forms of Di George syndrome, immunological reconstitution can be obtained by fetal thymus transplantation. It is expected that, in the near future, pure stem cell transplants and gene transplants will develop and will provide remarkable solutions for the therapy of a large number of diseases. PMID- 3324406 TI - Fetal liver transplantation in aplastic anemia and leukemia. AB - This study reviews results of fetal liver transplantation in hematologic disorders including aplastic anemia, leukemia and thalassemia. One hundred and twenty two patients received transplants for aplastic anemia; engraftment was reported in 4 patients; graft-versus-host disease (GvHD) did not occur. Complete and partial responses were reported in one-half of patients, the majority of whom had no evidence of engraftment. Thirty-nine patients received transplants for leukemia. Transient engraftment was reported in 40% and two developed GvHD; survival extended to more than 2 years. The higher rate of engraftment in patients with leukemia suggests a role of pretransplant immune suppression. The risk of GvHD appears to be low despite complete HLA-mismatching. These data suggest a possible role for fetal liver transplantation in man. Future studies should probably be based on preclinical data obtained in large animal models. PMID- 3324407 TI - [Ultrastructure and the number of nucleoli in the neurons of the rat cerebellar cortex]. AB - The ultrastructure and number of nucleoli in rat cerebellar nervous cells (the Purkinje and granule cells) were studied using the silver staining procedure and serial ultrathin sections. In the Purkinje cells one large nucleonemal nucleolus about 4 mcm in diameter was usually observed; fibrillar centers are weakly expressed. About 6% of the Purkinje cells had two nucleoli different in size. In granule cells 2-3 nucleoli about 1 mcm in diameter were detected. They contained a distinct fibrillar center and a dense fibrillar RNP-component, RNP-granules were barely visible. These data show that the Purkinje cells are more active transcriptionally than granule cells. The distinctions in the ultrastructure and number of nucleoli in the Purkinje and granule cells correspond to an earlier reported hypothesis about the intra- and interpopulation heterogeneity of cerebellar nervous cells for topography of ribosomal genes. PMID- 3324408 TI - [Polyploidization dynamics of tertiary trophoblast giant cells in the rat placenta]. AB - Polyploidization peculiarities of tertiary giant trophoblast cells during their active detaching from the ectoplacental cone and migrating into decidua basalis are investigated. On the 12th day of gestation, the ploidy of the majority of cell nuclei varies within 4-8c, although there are a few 16c and 32c nuclei. On the 13th and 14th days of gestation, the ploidy level of tertiary giant trophoblast cells enhances; 8c and 16c nuclei prevail, the percentage of 32c nuclei increases, 64c nuclei arising. The ploidy level of tertiary giant cell coincides with the average and/or maximum ploidy degree of precursor cell populations. The significance of polyploidy as indispensable condition of differentiation of the trophoblast cells that actively invade into maternal tissues is discussed. PMID- 3324410 TI - Light microscopic, immunocytochemical and ultrastructural study of a case of Sertoli cell tumor of the testis. AB - A case of testicular specialized gonadal stroma tumor was evaluated by histologic, ultrastructural and immunohistochemical techniques in a young adult male patient. The neoplastic cells were organized in cords or tubular structures delimited by a basement membrane. The ultrastructural findings suggested a diagnosis of a partially differentiated Sertoli cell tumor. This was also supported by the presence of a vimentin rich cytoskeleton, which is normally present in Sertoli and Leydig cells. The tumor cells did not secrete steroid hormones, as suggested by clinical findings, as well as by hormonal, immunohistochemical, and ultrastructural observations. PMID- 3324409 TI - Chronic lymphocytic leukemia (B-cell) in the course of polycythemia vera. Description of a case with an unusual chromosomic anomaly. AB - The present paper describes the case of a patient who developed a B-cell chronic lymphocytic leukemia (B-CLL) 15 months after the diagnosis of polycythemia vera, which had been treated only with phlebotomies. In spite of lymphocytosis and the clinical signs and symptoms of leukemia, the patient exhibited at the same time presumptive elements of polycythemia (high LAP index levels, a high number of neutrophils). Cytogenetic investigations, carried out after the appearance of B CLL, revealed the presence of an unusual abnormality (18 p+) both in bone marrow not stimulated by mitogens and in PWM-stimulated circulating lymphocytes. This case, which is the ninth of its kind described in the literature, offers some interesting observations about the association between myeloproliferative and lymphoproliferative syndromes. PMID- 3324411 TI - Congenital segmental dilatation of the colon with heterotopic esophageal mucosa. PMID- 3324412 TI - Hydrops of the gallbladder in an infant. PMID- 3324413 TI - [Methylglyoxal: metabolism and biological activity]. AB - The enzymic formation of methylglyoxal from dihydroxyacetone phosphate and aminoacetone (metabolites of carbohydrates and proteins) is considered. Methylglyoxal transformation into lactic and pyruvic acids is related to energy metabolism, catabolism and anabolism dissociation processes in carbohydrates and proteins, and, probably, to maintenance of asymmetrical entropy in vivo on the constant level. Attention is paid to the methylglyoxal inhibition of enzymes, its interaction with glutathione and polyamines affecting the mechanisms regulating protein synthesis and cellular division. The methods for obtaining and quantitative determination of methylglyoxal are described. PMID- 3324414 TI - [Cochlear implants. A review of a new treatment of deafness]. PMID- 3324416 TI - [Acute myeloid leukemia]. PMID- 3324415 TI - [Prevention of empyema in lung surgery. A prospective, randomized study]. PMID- 3324417 TI - [Post-apoplectic epilepsy. A review of the most recent literature on epilepsy following cerebral apoplexy]. PMID- 3324418 TI - [Cranial ultrasonography in newborn infants. A method of demonstration intracranial abnormalities]. PMID- 3324419 TI - [Side-effects of lumbar metrizamide myelography in ambulant patients and patients confined to bed]. PMID- 3324420 TI - [Suicide among children and adolescents 1970-1985]. PMID- 3324421 TI - [Postmenopausal hormone therapy]. PMID- 3324422 TI - [Rupture of the quadriceps tendon and quadriceps muscle. 13 cases treated at an orthopedic surgery department 1977-1983]. PMID- 3324423 TI - [1 versus 2 scalpels for surgical incision! Extra scalpels]. PMID- 3324424 TI - [Primary suturing of subcutaneous abscesses in orthopedic surgery patients. A prospective randomized study]. PMID- 3324425 TI - [Captopril and rheumatoid arthritis]. PMID- 3324426 TI - [Ultrasound studies of hypertrophic pyloric stenosis]. PMID- 3324427 TI - [Cleansing of the colon for roentgen studies]. PMID- 3324428 TI - [Congenital neuroblastoma discovered by a prenatal ultrasound study in the 36th week of pregnancy]. PMID- 3324429 TI - [Unstable angina pectoris, acute myocardial infarct, sudden heart death. Patho anatomy and pathophysiology]. PMID- 3324430 TI - [Appendiceal swelling]. PMID- 3324431 TI - [Pyomyositis]. PMID- 3324432 TI - [Neuropathy of the femoral nerve as a complication in anticoagulant treatment]. PMID- 3324433 TI - [Pulmonary sarcoidosis in Scandinavia 1950-1980. Clinical, epidemiological and prognostic aspects]. PMID- 3324434 TI - [Control of bladder tumors. Transabdominal ultrasonic scanning versus cystoscopy]. PMID- 3324435 TI - [Extracranial pseudo-aneurysm of the carotid artery following seat belt injury]. PMID- 3324436 TI - [Consensus development conference: prevention and treatment of osteoporosis]. PMID- 3324437 TI - [Functions of a multidisciplinary pain clinic for cancer patients]. PMID- 3324438 TI - [The nephrotoxicity of methicillin and dicloxacillin. A comparison on the basis of a review of the literature supplemented by 2 case reports of dicloxacillin induced acute interstitial nephritis]. PMID- 3324439 TI - [Carotid sinus massage. Examination technic, diagnostic and therapeutic use]. PMID- 3324440 TI - [Preventive antibiotic treatment in amputation of the lower extremity for ischemia]. PMID- 3324441 TI - Treatment of bacterial infections of the female urinary tract by immunization of the patients. AB - In an open comparative study 400 patients with urinary tract infections were randomly allocated to two treatment groups. In 202 patients an immune stimulation against uropathogenic bacteria was produced with a new preparation, SolcoUrovac, and only in exceptional cases with pronounced symptomatology was antibiotic therapy given, while in the control group (n = 198) all patients were treated with nitrofurantoin or with another appropriate antibiotic, according to the antibiogram. In the subsequent 12-month observation period 28 infections occurred in 23 patients of the immune-stimulated group and 84 in 47 patients of the control group. This difference is statistically significant (p less than or equal to 0.001). The preventive effect of the SolcoUrovac therapy was particularly impressive in patients with recurrent urinary tract infections. Thirty-two patients from each group with similar case histories, as matched pairs, were evaluated separately. The relapse rate in the 12-month observation period amounted to 2 re-infections in the group treated with immunotherapy and to 29 in the control group. All side-effects were recorded. No adverse effects were observed in pregnant women or in their offspring. PMID- 3324442 TI - A new method for early detection of renal allograft rejection. Gel high performance chromatography of urinary IgM. AB - We developed a new device utilizing high-performance chromatography to measure urinary IgM protein in renal transplant recipients. With this device we were able to obtain a reliable result in less than 2 h, requiring much less time than using the conventional method. Urinary IgM was found in 22 of 23 posttransplantation patients (96%) during acute rejection. An increase in urinary IgM excretion was noted 2-3 days before the appearance of clinical signs of acute rejection. PMID- 3324443 TI - Transferrin receptor expression by human bladder transitional cell carcinomas. AB - The expression of transferrin receptors (TFR) by normal and neoplastic urothelial cells was studied in "control" patients and in patients with transitional cell carcinoma of the bladder. These tumours were graded independently and consisted of 19 grade I, 30 grade II and 19 grade III lesions. TFRs were identified using a monoclonal antibody specific for TFR (OKT9) in an immunofluorescent or avidin/biotin-immunoperoxidase technique on fresh frozen sections. TFRs were not detected on normal urothelium. However, positive staining was found to increase with increasing pathological grade and stage of the tumours, ranging from 31.6% of grade I to 78.9% of grade III tumours and 51.2% of pTa (mucosa only lesions) to 87.5% of pT2/pT2+ (muscle invasion +/- deeper) primary urothelial malignancies. PMID- 3324445 TI - [What's new in urology?]. PMID- 3324444 TI - Expression of proto-oncogenes in xenografts of human renal cell carcinomas. AB - In a recent paper, we described the expression pattern of proto-oncogenes in primary human renal cell carcinoma [12]. To test the possibility of using xenografts as a useful alternative for such studies, we analyzed xenografts of a number of human renal cell carcinomas in nu/nu mice. Xenografts included RC2, RC14, RC21, RC43 and NC65. Northern blot analysis indicated that c-Ras was expressed in all these xenografts. The identity of the ras transcripts in the individual xenografts was further specified as c-Ha-ras, c-Ki-ras or N-ras. Expression of c-myc and the p53 gene was also found in a number of these tumors. Only RC21 failed to express the c-myc or the p53 gene. In all xenografts, a 3.0 kb c-fes/fps mRNA was present. In RC2, RC14, RC21 and RC43, low levels of the 4.8 kb ab 1 transcript were detectable. Transcripts of myb and sis could not be detected in any of the xenografts. The results indicated that the expression pattern of a variety of proto-oncogenes in xenografts of human renal cell carcinomas was similar to that in the primary tumors. PMID- 3324446 TI - [Percutaneous reanastomosis of a transplanted kidney]. AB - A case of a successful percutaneous reanastomosis of a transplanted kidney is reported. The kidney had already been operated on several times. The kidney ureter anastomosis was occluded. Using a combination of ureteroscopy and the percutaneous technique, the old anastomosis was bypassed and a new one was made. PMID- 3324447 TI - [Sonography in the early detection of non-palpable second testicular tumors: a prospective study]. AB - As part of the tumor aftercare service afforded by our policlinic, 91 patients were examined one to six times in 18 months following radical orchiectomy for testicular germ cell tumors. The period of observation averaged 35 months (3-147) after the contralateral removal of the testicle. In addition to the usual routine checks, sonography of the residual testicle also formed part of the established followup protocol. Among these patients sonography identified in residual testicles 3 testicular tumors (3.3%) which had escaped detection on palpation. The existence of these second tumors was demonstrated 3, 25 and 38 months following contralateral orchiectomy. In all instances the second lesion differed from the first tumor in histology. In another patient a plum-sized malignancy was revealed within a large concurrent hydrocele by scrotal sonography carried out 18 months following preceding contralateral orchiectomy. Thus, our group of patients gave an incidence of 4.4% for second primary testicular tumors, a poor known incidence rate. Such malignancies can be spotted early by ultrasound, they are genetically obscure just as the increasing morbidity of the unilateral disease. These results urgently suggest that after semicastration for testicular germ cell tumor the residual testicles should be regularly scanned by ultrasonography at four-month intervals. Retrograde sonography has been shown to detect even those small occult testicular tumors which pass unnoticed until metastasizing. PMID- 3324448 TI - [Sonography of the scrotal contents]. AB - In 394 patients with various urological symptoms, the content of the scrotum was examined sonographically. 71 testicular lesions were found, 194 extratesticular pathologies were diagnosed. In 69% the enlargement of the testicle was due to a tumor, in 4 patients due to acute orchitis and in 3 patients due to acute torsion. An unilateral smaller sized testicle was found in chronic inflammation [5], cryptorchism [9], hypoplastic testicle [2] and after corticoid medication [1] and radiation therapy [1]. In normal sized testicles 8 tumors, 19 fibromas of the tunica albuginea, 2 scars after trauma and 1 haematoma were found sonographically. In 91% of patients with epididymitis the epididymis was enlarged. The echo structure was altered in 74%, in 13% abscesses were found. Sonography was useful in evaluation of scrotal herniation, especially when combined with hydroceles. Varicoceles were better detected and graduated by sonography than by clinical examination. PMID- 3324449 TI - [Correction of nose deformities after plastic surgery of unilateral cleft lip]. AB - The author describes the method of operation for the elimination of the recurrent flat wing and tip of the nose after reconstructive chilorhinoplasty in unilateral cleft lips. The method of chilorhinoplasty was used in more than 500 patients. The symmetry of the nose tip was achieved in 85% of the cases which shows the prospects of introduction of the method into wide clinical practice. PMID- 3324451 TI - [Use of ultrasonics in the fixation of autologous skin transplants]. AB - Based upon his clinical experience the author proves advantages of the ultrasonic welding for the transplant fixation in skin plasty with using cyacrine as joining material. PMID- 3324450 TI - [Results of using autologous and demineralized allogeneic bone transplants in reconstructive operations on the mandible in children with the syndrome of the first and second branchial arches]. AB - A comparative clinico-roentgenological assessment of results of transplantation of auto- and allogenic demineralized transplants in reconstructive operations on the mandible was made in 58 children with the syndrome of the first and second branchial arches aged from 1 to 14 years. It was found that the substitution of the transplants by a new bone tissue was developing similarly. Allogenic bone transplants have a number of advantages over autotransplants: a simpler treatment and modelling the absence of an additional trauma to the child and a shorter duration of the operation. PMID- 3324452 TI - [Errors and complications of microsurgical autologous transplantation of tissue in trauma]. AB - Possible errors and complications are analyzed basing on the experience with microsurgical autotransplantation of 87 tissue complexes fulfilled in 81 patients with traumas. Various complications were established in 25 out of 82 patients (30.4%). Acute disturbance of the transplant blood circulation was noted in 17.2%. Reoperations on the vessels reduced the incidence of failures to 8% of all the transplanted complexes of tissues. PMID- 3324453 TI - [The main ways of improving results in treating combined injuries of the major vessels of the extremities]. AB - Based on an analysis of the surgical treatment of 240 patients with traumas of the main extremity vessels (147 associated traumas included) the authors show that favorable outcomes of such injuries are due to such factors as timely diagnosis, successful struggle with the traumatic shock and blood loss, adequate and skillful technique of surgical measures, adequate treatment of concomitant injuries and character of therapy in the postoperative period. PMID- 3324454 TI - Differentiation of Salmonella typhimurium DT204c by plasmid profile and biotyping. AB - Seventy per cent of the United Kingdom isolates of Salmonella typhimurium from calves are phage type 204c and the study of the epidemiology of this organism requires additional methods of strain characterisation. This paper describes the applications of biotyping and plasmid-profile analysis for this purpose. One hundred and eleven isolates from 73 outbreaks of disease were examined. All belonged to the same primary biotype, although strains from 39 of the outbreaks differed in secondary tests in failing to ferment m-inositol at 25 degrees C. Four different antibiotic resistance patterns were detected among the isolates, which possessed seven distinct plasmid profiles. The spread of a distinct type through the calf marketing chain was investigated by using these techniques. PMID- 3324455 TI - Prof. Dr. J. G. van Bekkum's farewell. Festschrift on the occasion of his retirement. PMID- 3324456 TI - Epizootiology of swine fever. AB - In countries with an intensive pig production system, swine fever (SF), where present, may be regarded as one of the economically most important pig diseases. Although reservoirs of virus and pathways of transmission are well understood, field experience has shown that the disease is extremely difficult to eradicate, especially in countries with intensive pig breeding. The virulence of the strains circulating in the field and the measures applied to control the disease determine to a large extent the course of an epizootic. Outbreaks of highly virulent strains are readily recognised. Epizootics caused by low virulent strains are characterised by indistinct signs of disease, slow spread of virus through the herd and the comparatively important role of the 'carrier sow syndrome'. The latter phenomenon may result in the birth of healthy looking but persistently infected and immune-tolerant piglets. This and the occurrence of chronic infections are largely responsible for the perpetuation of the virus in the pig population. The 1982-1985 epizootic of SF in the Netherlands showed an almost equal prevalence of outbreaks in breeding and fattening herds. In proportion to the number of herds in the country, there was in both categories an approximately linear relationship between the risk of infection and the size of the herds. The proportion of affected breeding herds increased as mass vaccination of areas at risk was started earlier in the epizootic. In close-knit communities with large breeding units, man should be regarded as the single most important factor in the herd-to-herd transmission of the virus, whereas in fattening units and in areas with small pig farms, transport and introduction of infected pigs into herds accounts for the majority of outbreaks and for the spread of the disease. Farms visited by persons handling pigs subsequent to contact with an infected herd should, therefore, be included in the epizootiological investigations. Virological and serological methods are indispensable in order to confirm or to rule out the possibility of infection of suspected contacts, especially in outbreaks caused by strains of low virulence. Continuous education of farmers regarding the importance of maintaining precautionary measures against the introduction of contagious diseases and, in the case of an advancing epizootic, special instructions to all people entering piggeries, would contribute greatly to reducing the untraceable pathways of SF spread. PMID- 3324457 TI - In vitro adhesion of K88ab-, K88ac- and K88ad-positive Escherichia coli to intestinal villi, to buccal cells and to erythrocytes of weaned piglets. AB - The phenotype of 21 weaned piglets, concerning adhesion of Escherichia coli possessing K88ab, K88ac or K88ad fimbriae to pig cells, was determined in an in vitro assay. Comparison was made with adhesion of these three K88 variant strains to buccal mucosal epithelial cells and to erythrocytes (haemagglutination) in the same piglets. Whereas adhesion of the three K88 variant strains to intestinal villi was piglet specific, buccal cell adhesion (BCA) and haemagglutination (HA) were not. The K88ab strain was weakly adhesive or non-adhesive in the BCA and negative in the HA test. K88ac strains consistently gave negative and K88ad consistently gave positive results in both assays. After washing the bacteria with phosphate-buffered saline, the K88ab strain revealed a positive HA test. Neither the BCA, nor HA test can be used to determine the pig intestinal adhesive phenotype. PMID- 3324458 TI - Capsule types of Klebsiella pneumoniae isolated from the genital tract of mares with metritis, extra-genital sites of healthy mares and the genital tract of stallions. AB - A survey of K. pneumoniae was performed on cervical swabs, feces and nasal swabs of mares and on samples from the genital tract of stallions from 1980 to 1986 in south-western Hokkaido, Japan. K1 was the predominant type (79 of 88, 89.8%) in the metritis cases due to K. pneumoniae in mares of racing breeds. The same type was isolated from semen and swabs of the fossa glandis of 6 of 20 (30.0%) of the stallions of racing breeds. Heavily encapsulated and less heavily encapsulated K1 strains were isolated from the stallions. Mares bred to stallions carrying heavily encapsulated strains developed metritis, while those bred to stallions carrying less heavily encapsulated strains did not. K39 was isolated from cervical swabs solely from metritis-infected mares of draft breeds and not from any mares of the racing breeds examined. Untypable strains were isolated from cervical swabs in 7 of 88 (8.0%) metritis cases of mares of racing breeds and from semen in 7 of 19 (36.8%) stallions of racing breeds and they were predominant in feces (19 of 21, 90.5%) and nasal swabs (3 of 4, 75.0%) of healthy mares of racing breeds. PMID- 3324459 TI - Bovine leukocyte phagocytosis and bacteria killing monitored by intracellular acridine orange fluorescence and extracellular fluorescence quenching. AB - The time course of phagocytosis and intracellular killing of serum-opsonized Escherichia coli K12 and Staphylococcus aureus SG511 by glass-adherent bovine peripheral blood polymorphonuclear leukocytes (PMNLs) and cultured monocytes (macrophages) was monitored by fluorescence microscopy of single cells using the acridine orange (AO)/crystal violet (CV) technique. After interaction of glass adherent leukocytes (20, 40, 60 min, 37 degrees C) with opsonized bacteria, cells were stained with the fluorescent dye AO. Living bacteria stained green, dead bacteria stained orange. The addition of CV to AO-stained bacteria quenched the fluorescence of extracellular bacteria only. CV does not penetrate living bovine PMNLs which allows the discrimination of ingested (fluorescent) and extracellular (nonfluorescent) bacteria during attachment and phagocytosis of bacteria by adherent PMNLs. We investigated quantitatively phagocytosis and intracellular killing of serum-opsonized bacteria by bovine PMNLs from 22 bulls of 4 different Swiss dairy breeds. Within 60 min maximum uptake (approximately 12 bacteria/PMNL) and killing (approximately 80%) of serum-opsonized Escherichia coli K12 and Staphylococcus aureus SG511 were achieved. The AO/CV technique was also used to quantify the uptake and intracellular killing of serum-opsonized Escherichia coli K12 by cultured monocytes (macrophages). Within 60 min maximum uptake of bacteria (approximately 16/MO) was achieved; approximately 83% of bacteria were killed. PMID- 3324460 TI - A functional and biochemical analysis of bovine class II MHC antigens using monoclonal antibodies. AB - Monoclonal antibodies (MAbs) reacting with bovine (2) ovine (3), murine (1) or human (1) Class II MHC antigens were examined for reactivity with bovine peripheral blood leucocytes (PBL) and lymph node cells (LNC) by immunofluorescence, immunoprecipitation and the capacity to inhibit mixed lymphocyte responses (MLR), lectin- and antigen-induced blastogenesis. The 6 MAbs identified comparable percentages of Class II positive lymphocytes in PBL (40.8 to 54.2%) and LNC (6 to 11.5%) regardless of BoLA-A phenotype. Immunohistological staining of Class II MAb was localized principally to the lymphoid follicles in lymph nodes and to isolated epithelial reticular cells in the thymus. The anti Class II MAb immunoprecipitated alpha- and beta- chains of 26-29K and 32-34K, respectively. These MAb inhibited proliferative responses in the MLR by between 25 and 74%, and diminished blastogenesis induced by specific antigens (purified protein derivative + PPD and ovalbumin) and B-lymphocyte mitogens (PPD, lipopolysaccharide and dextran sulphate) by between 45 and 75%, regardless of BoLA-A phenotype. In contrast, proliferation in response to concanavalin A and phytohaemagglutinin were unaffected by the anti- Class II MAb. Similarly these MAb did not affect lysis by cytotoxic T-lymphocytes, the activity of which was depressed by anti-Class I MAbs and monospecific alloantisera. PMID- 3324461 TI - K88 variants K88ab, K88ac and K88ad in oral vaccination of different porcine adhesive phenotypes. Immunological aspects. AB - Sows of different adhesive phenotypes were vaccinated orally during the last 4 weeks of gestation with K88-positive Escherichia coli. Sows susceptible to adhesion by the K88 variant of the vaccination strain produced a significant IgA class specific anti-K88 response in colostrum and milk and post-farrowing serum. Indications for an IgM and IgG-class specific anti-K88 response were also found in this group but only in milk. In sows resistant to adhesion by the K88 variant of the vaccination strain only an IgA-class specific anti-K88 antibody response was found in mammary secretions and in post-farrowing sera, but titres did not reach the high values of the former group. The response in the second group was attributed to the frequent administration of large quantities of K88-positive E. coli which to some extent can be compared with a colonization effect. Specificity for the serological components of the K88 variants was detectable in colostral IgA of sows susceptible to the vaccination strain only. PMID- 3324462 TI - Adjuvants. AB - A number of adjuvants of importance in veterinary vaccines are reviewed. These include mineral salt adjuvants, oil adjuvants, hydrophilic and hydrophobic bloc polymers, hydrocarbons and surface active agents. The current and future applications of these substances and their possible modes of action are discussed. Creation of an adjuvant register by the newly formed European Adjuvant Group should facilitate accumulation of information on adjuvants. PMID- 3324463 TI - Regulation of immunity by anti-idiotypic antibodies. AB - The immune system is under control by idiotypic-anti-idiotypic regulation. This control can operate according to dose of antigen, age of the individual, route of administration etc. and function as a specific stimulator or inhibitor of immune reactivity against a defined antigen. Data already exist to justify the statement that our immune system contains within itself all foreign structures against which it can react in the form of anti-idiotypic receptors. These "foreign" structures as displayed at the anti-idiotypic level may be more or less like their true counterparts outside the body and can serve as immunogen, for instance as vaccines. The regulation of immune reactivity via idiotypic interactions may also serve as a potent regulatory of fetal-neonatal immune reactivity causing it to resemble that of the mother. Potential clinical use of auto-anti-idiotypic immunity can thus be foreseen both with regard to elimination of unwanted immune reactivity as well as induction of wanted immunity. PMID- 3324464 TI - Bovine interleukin 2: cloning, high level expression, and purification. AB - We utilized a human IL2 probe to isolate bovine IL2 sequences from a lymph node cDNA library. Bovine IL2 was subsequently expressed in both bacteria and yeast. Using a rapid, two-step purification scheme, we have been able to isolate over 20 mg/l of homogenous bovine rIL2 secreted from the yeast. The availability of sizable quantities of bovine rIL2 should make it possible to ascertain potential therapeutic or prophylactic utility of this lymphokine in cattle. PMID- 3324465 TI - Transfection of genes encoding lymphocyte differentiation antigens: applications in veterinary immunology. AB - The work conducted so far in this laboratory has demonstrated the application of the use of genes encoding lymphocyte differentiation molecules, in the isolation of homologous genes from other mammalian species, by the technique of cross species DNA hybridization. The studies have also highlighted the use of transfection as a means of obtaining expression of genes, either from total genomic DNA or cloned in plasmids, which encode lymphocyte antigens. Preliminary work presented in this paper demonstrates the application of these technologies in the isolation and expression of genes for lymphocyte antigens from species in which the gene products have not been fully defined. We favour this approach because it may allow isolation and definition of important immunological molecules independently of the existence of specific antibodies. It therefore seems the most direct way to avoid the frustrating randomness in production of anti lymphocyte subset-specific monoclonal antibodies, and to shorten the time and effort needed to define the specificities of such reagents. Furthermore, the cDNA clones isolated from alternate species (in this case the bovine) have a use in classical immunological studies apart from the application of antibodies made to their products in veterinary immunology. That is, comparisons of the DNA sequences of lymphocyte differentiation antigens from different species provide much important information about structural or functional elements of evolutionarily conserved proteins involved in generation of immune responses. PMID- 3324466 TI - Nematode antigens in protection, diagnosis and pathology. AB - A thorough study of parasite antigens is a prerequisite for control programmes based on protection by vaccination, accurate serodiagnosis and perhaps immune modulation to diminish pathological sequelae. Stage specific surface secreted and somatic antigens may be of particular value in proceeding towards these goals. The design of vaccines is most appropriately focused on surface antigens. With respect to pathology, certain antigens must stimulate humoral and, or cellular immune responses which are responsible for the undesirable immunopathologic consequences of the disease. The ultimate objective, therefore, is identification of those particular antigens followed by appropriate down regulation of the immune system in order to delete such potentially harmful immunological reactions. The relevant illustration presented in this context is an interesting correlation between one particular clinical condition of onchocerciasis ("sowda") and the serological response, defined both in terms of the parasite antigen and an immunoglobulin class restricted antibody response. Current parasitological methods of diagnosis consistently underestimate parasite prevalence. Failure to detect low level patent infections incurs the risk of having a reservoir capable of perpetuating infections. There is, then, an urgent requirement for accurate serodiagnosis, to be used in association with, and for the evaluation of, drug treatment and vector elimination in parasite control programmes. Given the high sensitivity of current immunoassay technology, the only bar to establishing the necessary immunological tests is the choice of suitably specific antibody-antigen systems. Once these are identified, a combination of recombinant nucleic acid biochemistry and hybridoma technology should provide the necessary reagents for inexpensive, robust and specific diagnostic tests. In addition, it may not be many years before the ubiquitous RIA and ELISA technology gives way to the newly developing biosensor systems. Finally, given the sensitivity and specificity of today's nucleic acid hybridization techniques, we may soon expect to see specific identification of infective larvae in their vectors of this, a cloned DNA probe specific for Onchocerca volvulus, and with potential for the detection of infective larvae in blackflies is described. PMID- 3324467 TI - Immunity to Eimeria infections. PMID- 3324468 TI - Synergism between antibody and neutrophils in the ruminant mammary gland. AB - Immunological activities of the mammary gland are important both as a means of transferring immunity from mother to young and for defending the mammary gland itself against infection. The presence of immunoglobulins G1, G2 and A, and of neutrophils, macrophages and complement in the ruminant mammary gland is described, in particular the synergistic role of antibody and neutrophils is discussed and studies of immunization against staphylococcal mastitis are outlined. PMID- 3324469 TI - Enzyme immunoassay: observations on aspects of quality control. PMID- 3324471 TI - Lymphocyte antigens of sheep: identification and characterization using a panel of monoclonal antibodies. AB - A panel of monoclonal antibodies has been developed and used to identify and characterize the lymphocyte antigens of sheep. These studies have shown that sheep lymphocyte antigens display similar, if not identical, tissue distributions to their analogues in other species. Some of the major sheep antigens, including CD5, CD4, CD8, SBU-T19, Pgp-1, LCA and the MHC antigens, are described in detail. PMID- 3324470 TI - Immunologic reconstitution of foals with combined immunodeficiency. AB - Thirty-eight foals with combined immunodeficiency (CID) received transplanted fetal liver cells, fetal liver and thymus cells, histocompatible bone marrow cells, or equine lymphocyte antigen (ELA) haploidentical bone marrow cells in an attempt to reconstitute their deficient immune systems. Engraftment was infrequent, partial, and unpredictable when fetal cells were employed. Three of five CID foals receiving ELA haploidentical bone marrow cells demonstrated partial reconstitution, but engraftment was only temporary. Administration of histocompatible bone marrow cells resulted in rapid, full and sustained engraftment. PMID- 3324472 TI - [Organization of the medical services to the Soviet troops during the defense of Stalingrad (on the 45th anniversary of the battle)]. PMID- 3324473 TI - [Medical supplies at the time of the battle for Stalingrad]. PMID- 3324474 TI - [The oldest military sanatorium (on the 150th anniversary of the Saki Central Military Sanatorium)]. PMID- 3324475 TI - [Ekaterina Mikhailovna Bakulina (on the 175th anniversary of her birth)]. PMID- 3324476 TI - [Achievements in the fields of balneology, physical therapy and medical rehabilitation during 70 years of Soviet rule]. PMID- 3324477 TI - [Role of the State Institute of physiotherapy in the development and use of physical methods of treatment (II)]. PMID- 3324478 TI - [Transforming activity of DNA and proteins in continuous cell cultures and the safety of biologicals]. PMID- 3324479 TI - [Virological studies in fatal outcomes in influenza and its complications in adults during the period of influenza A (H3N2) virus circulation from 1969 to 1983]. AB - In the period of circulation of influenza A (H3N2) virus, 1969-1983, we examined virologically the autopsy specimens from 69 adults who died of influenza and its complications. Immunofluorescence examinations of organ impressions and infected cultures as well as virus isolations were used for postmortem laboratory diagnosis. Influenza viruses were isolated postmortem in all age groups, predominantly in older subjects (over 60), both in cases of early and late (after 7 days) deaths. The viruses were isolated more frequently from respiratory organs, less so from the blood, parenchymatous organs, cerebral tissue. A decrease in the number of lethal outcomes in adults and in the number of positive virus isolations postmortem was noted with the emergence of an antigenic drift variant Victoria/75. Simultaneous employment of several laboratory tests verified virologically the diagnosis of influenza in adults postmortem in 85% of the cases. PMID- 3324480 TI - [Determination of antibodies to the AIDS virus and the viral antigen by an immunoenzyme method using peroxidase and beta-lactamase]. AB - The ELISA test using beta-lactamase for the detection of anti-AIDS virus antibodies and virus antigen in serum is described. The properties of this test system are compared with those of the system based on horseradish peroxidase conjugates. PMID- 3324481 TI - [Optimization of conditions for detecting the internal proteins of influenza A virus in solid-phase immunoenzyme analysis]. PMID- 3324482 TI - [Contribution of L. V. Gromashevskii to the epidemiology of viral infections (on the centenary of his birth)]. PMID- 3324484 TI - [Antibodies against soluble nuclear antigens in rheumatic diseases]. AB - The basic contemporary methods for determination of serum antibodies against DNA are compared. The immunoenzyme methods are recommended because of their accessibility. The high frequency of antibodies against DNA in lupous patients is pointed out. The antibodies against extractable nuclear antigens (Sm and RNP) in rheumatic patients are also determined. The results are compared with these of a control group of healthy persons and patients with non-rheumatic diseases. The antibodies against extractable nuclear antigens are found most frequently in lupous patients. PMID- 3324483 TI - [Potentials and limits of ultrasonic diagnosis in gastroenterology]. AB - The great diagnostic value of ultrasonic tomography in the diagnosis of liver, biliary, pancreatic, gastric, intestinal, abdominal and retroperitoneal disease is reviewed and proved. Best results can be achieved in the indications for its application and the potentialities of the method are well known. The sonographic results should always be assessed with the clinical, laboratory and other instrumental data. The faulty diagnoses are due not to the method itself but to the incompetent interpretation of the sonographic images and to the lack of knowledge for the scope and limitations of sonography. PMID- 3324485 TI - [Fibronectin--its clinical importance, chemical structure and biological interactions]. PMID- 3324486 TI - [Current status of the Q-rickettsial endocarditis problem and the 1st case reported in Bulgaria]. AB - A vast literary review on Q-rickettsial endocarditis is presented--spread, frequency, predilection, clinical course, laboratory findings, diagnosis, treatment, prognosis. The first case of Q-rickettsial endocarditis in Bulgaria is reported. The case was proved by the high titre of the specific antibodies while the patient was still alive and post mortem by visualizing the causative agent in the aortic valve and by its isolation through inoculation of material from the aortic valve. The infection was not influenced by high doses of penicillin, gentamycin and brulamycin but was suppressed by vibramycin in combination with lincomycin and biseptol. The lethal outcome was due to severe heart failure. It is suggested that other cases of Q-rickettsial endocarditis should be expected since Q-fever is widely spread in Bulgaria and the characteristics of the disease, its diagnosis and treatment ought to be well known. PMID- 3324487 TI - [The delta hepatitis virus--what we know 10 years after its discovery]. PMID- 3324488 TI - [Incidence of carotid pathology in patients with chronic arterial insufficiency of the extremities]. AB - The frequency of carotid pathology and of some risk factors in the genesis of atherosclerosis was studied in 189 patients. The patients were classified into two groups: group A--58 persons without clinical data for atherosclerosis (conditionally healthy persons); group B--131 patients with chronic arterial failure in the limbs. By means of Doppler sonography a low incidence of carotid pathology was established in group A (3.4%) and a significantly higher incidence in group B (38%). The results were confirmed angiographically. The risk factor were more frequent in group B than in group A. The atherosclerotic process affects simultaneously the peripheral, carotid and coronary arteries. This implies active screening of the carotid arteries in patients with clinically manifested chronic arterial failure in the limbs of with ischemic heart disease. The method of Doppler sonography is the most suitable for that. PMID- 3324489 TI - [Clinical, laboratory and morphological characteristics of mesangioproliferative glomerulonephritis]. AB - The mesangioproliferative glomerulonephritis (MPGN) is the most frequent morphological type of primary glomerulonephritis and it was found in 42.7% of the patients studied. The MPGN is not a single nosologic entity which is proved by the immunofluorescent findings, clinical and laboratory characteristics. Several immunofluorescent types with characteristic clinico-laboratory constellation and different etiopathogenesis could be defined. The most clearly defined types of MPGN are those with leading IgA and IgM precipitates. The similar immunofluorescent findings, clinico-laboratory characteristics, course and susceptibility to symptomatic and pathogenetic treatment in MPGN with leading IgG and C3 precipitates lead to the suggestion that there may exist different "phase" states in the course of the different types of MPGN. In spite of some characteristic differences in the symptomatology and course of the different types of MPGN their differentiation is possible only by kidney biopsy. PMID- 3324490 TI - [Arterial stenosis in kidney transplant patients]. AB - A short literary review is presented on the frequency and characteristics of the stenosis of the arterial anastomosis or of sections next to it in patients with transplanted kidney. The histories of three patients are reported. In two of the patients in the 6th and 7th month following the transplantation a severe arterial pressure appeared and a systolic murmur could be heard medially from the transplanted kidney. By renal vasography a marked stenosis of the anastomosis of the renal artery with the hypogastric artery was found. The stenosis was not corrected in time which led to its thrombosis and explantation of the kidney. In the third patient the renal vasography did not reveal stenosis of the anastomosis. In this case the symptoms were due to a chronic crisis of rejection of vasal type. The appearance of severe persistent arterial hypertension 6-7 months after a kidney transplantation is a signal for possible stenosis of the arterial anastomosis which requires timely examination and surgical correction if found. PMID- 3324491 TI - [Indications for tonsillectomy]. PMID- 3324492 TI - [Fetal respiratory movements: a research problem or a clinical test?]. PMID- 3324493 TI - [Mechanisms of coronary pain and painless myocardial ischemia]. PMID- 3324495 TI - [Isolated accessory liver (hepar succenturiatum) at the neck of the gallbladder. Case report with review of the literature]. AB - We report on a 34 year-old female patient whose gallbladder was removed because of cholecystolithiasis. On histological examination of the fatty tissue surrounding the neck of the gallbladder an accessory liver was detected. Accessory liver tissue is nearly always an incidental finding at operations and autopsies. It arises in the vicinity of the gallbladder from residual liver cells in the caudal part of the embryonic liver anlage. In the differential diagnosis ectopic liver tissue has to be distinguished from other heterotopic tissues. Accessory livers may also be found in certain other organs and structures which lie in close proximity to the liver during fetal life. PMID- 3324494 TI - [Subacute cutaneous lupus erythematosus: clinical aspects, immunology and therapy]. AB - Subacute cutaneous lupus erythematosus (SCLE) is a distinct subset of cutaneous lupus erythematosus which is defined by clinical and immunological characteristics. With regard to clinical expression and prognosis, SCLE assumes an intermediate position within the spectrum of LE between purely cutaneous discoid and systemic lupus erythematosus. The main clinical characteristics of SCLE are extensive papulosquamous or anular lesions and photosensitivity. The disease is frequently associated with Sjogren's syndrome and systemic symptoms, mainly arthralgia. Renal involvement is, however, rare. Circulating Ro-antibodies represent the main autoimmune phenomenon. An immunogenetic disposition to develop SCLE is evidenced by the detection of the HLA-B8, DR3-phenotype in a large proportion of patients. Drug therapy comprises primarily glucocorticosteroids and antimalarials, but retinoids have recently also proved highly effective. PMID- 3324496 TI - [Thrombolytic therapy in fresh myocardial infarct]. AB - In this overview the characteristics have been defined of those patients with acute myocardial infarction to whom early thrombolytic therapy would offer a major benefit. However, this concerns only the 20% of all patients who are admitted to the hospital with acute myocardial infarction within the specified time limit. It is still unclear whether later thrombolytic therapy with the newer agents might offer benefit to other patients with acute myocardial infarction. Presently, it seems unlikely that patients admitted to the hospital more than six hours after onset of symptoms will benefit from any reperfusion strategy. Patients admitted up to 24 hours after onset of symptoms with symptomatic and extensive ischemia (usually located anteriorly) or with signs of cardiogenic shock constitute a group of high risk patients who might derive further benefit from late reperfusion (42). It is likely that in the near future the new generation of thrombolytic agents (rt-PA, rscu-PA and APSAC) will become first choice for the intravenous initiation of thrombolytic therapy. Then, the indications for either acute or delayed angiography might be different from the present ones. Further cost/benefit analysis will certainly be required to assess the additional value of intracoronary thrombolysis and coronary angioplasty after intravenous administration of rt-PA, rscu-PA or APSAC. The required capacity of catheterization laboratories and facilities for coronary angioplasty and bypass surgery will depend on the results of those analyses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324497 TI - [Therapy of multi-infarct dementia with nicergoline: double-blind, clinical, psychometric and EEG imaging studies with 2 dosage schedules]. AB - In a double-blind study, clinical, psychometric and neurophysiological changes were investigated in patients with MID treated by two different drug administration schedules of nicergoline (20 mg evenings versus 10 mg b.i.d.). 24 hospitalized patients (4 males, 20 females) with a mean age of 78 years were included according to the criteria of DSM-III, an Ischemic-Score of at least 7 points and a specific computed tomogram (CT). After a placebo-period of 2 weeks all patients were randomly assigned to an 8-weeks-treatment with either 20 mg nicergoline h.s. or 2 x 10 mg b.i.d. The evaluation of the detailed psychopathology by means of SCAG, CGI, NOSIE, Hamilton-Depressions-Scale and Mini Mental-Status, as well as psychometric investigations by means of the Nuremberg Aging-Inventory (NAI), thymophysic and psychophysiological measurements showed a significant improvement in both groups as compared with pre-treatment. This improvement was observed slightly earlier in patients with 20 mg h.s. than in those on the b.i.d. schedule. However inter-group-differences reached the level of statistical significance in only 2 variables. Neurophysiological investigations by means of topographic brain-mapping showed interesting relations between functional EEG-images and morphological CT-images. Vigilance-improving patients showed a better therapeutic response than those who did not show neurophysiological changes indicative of improvement in vigilance. Our findings suggest, that a single dose once daily was at least equal to the b.i.d. administration as far as therapeutic efficacy was concerned, even more so in the light of an expected improvement of compliance. PMID- 3324498 TI - Pouch versus esophagojejunostomy after total gastrectomy: a randomized clinical trial. PMID- 3324499 TI - The continent ileostomy. PMID- 3324500 TI - Motor function of the ileal J pouch and its relation to clinical outcome after ileal pouch-anal anastomosis. PMID- 3324501 TI - Restorative proctocolectomy with various types of reservoir. PMID- 3324502 TI - Biological effects of a reservoir at the end of the small bowel. PMID- 3324503 TI - The use of the cecum for cecocystoplasty. PMID- 3324504 TI - High-frequency ventilation. PMID- 3324505 TI - AIDS: overview and VA update. AB - Acquired immune deficiency syndrome (AIDS), a devastating disease with numerous masks (e.g., a primary neurosymptomatic disease), has now been reported in over one hundred countries of the world. Projections by the Public Health Service of the numbers of cases and fatal illnesses in the United States by 1991 stagger the imagination, and we are told that these projections may be understated. The Veterans Administration (VA) has not been immune to this disorder, over 2,000 cases of frank AIDS (as defined by the Centers for Disease Control [CDC] having been reported to VA's Central Office by 111 of the VA's 172 medical centers. These findings do not include AIDS-related complex (ARC) or other manifestations of human immunodeficiency virus (HIV) infection. Seventy-seven percent of this total have been reported from 22 of the VA's largest tertiary care centers. The VA has developed an action plan, one of whose features is the development of a direct discussion and collaboration with other federal health care agencies, including the military. Emphasis is to be placed on the exchange of information among these various executive branches and, most important, on the smooth transfer of patients with AIDS or ARC from the uniformed services into the VA's health care system. In addition to the primary goal of providing timely, compassionate care to these patients, the VA also has a commitment to the dissemination of information to our patients, their families, and our employees. PMID- 3324507 TI - Principles of laboratory isolation and identification of the human immunodeficiency virus (HIV). AB - Diagnosis of human immunodeficiency virus (HIV) infections has relied most frequently on detecting the presence of HIV antibodies in sera. In many situations, however, patients management can be significantly improved if the presence of HIV can be demonstrated in patients' specimens. In this review, the need and value of HIV isolation for confirming the diagnosis of HIV, for disease staging, and for monitoring the effectiveness of antiviral therapy are discussed. The steps involved in isolation of HIV, the cell systems permissive to HIV growth, and the procedures for virus identification are reviewed. Furthermore, methods available for the direct detection of HIV in patients' specimens are summarized. Although isolation of HIV is presently an elaborate procedure, as easier methods become available, it will play a large role in the management of HIV-infected individuals. PMID- 3324506 TI - Epidemic human immunodeficiency virus (HIV) infection among intravenous drug users (IVDU). AB - Human immunodeficiency virus (HIV) infection is epidemic among intravenous drug users (IVDU), particularly in the northeastern United States. IVDU are playing a critical role in the spread of HIV by infecting their heterosexual partners and children, as well as their needle-sharing partners. The epidemiology of HIV infection among IVDU is reviewed here, including a compilation of seroprevalence data. Relevant determinants of the future spread of HIV among IVDU are discussed, including the major risk factors for HIV seropositivity, the modes of HIV transmission, and aspects of the natural history of HIV infection in IVDU. The public health policy implications of these issues include the need for education of adolescents and the general public about the risks of drug injection and heterosexual intercourse with IVDU, as well as motivation of IVDU to stop injecting, never share injection paraphernalia, or, at least, clean needles effectively. PMID- 3324509 TI - [Neurologic complications of chronic alcoholism]. PMID- 3324510 TI - [Smallpox vaccination in Prussia up to the state vaccination law of 1874, with special reference to the Frankfurt (Oder) government district]. PMID- 3324511 TI - [Berlin's public health status 100 years ago. By Adolf Gottstein 1906]. PMID- 3324512 TI - [Adolf Gottstein (1857-1941) and public health in Berlin. An introduction to his essay "Berlins' public health status 100 years ago"]. PMID- 3324508 TI - Pathogenesis of human immunodeficiency virus infection and prospects for control. AB - In just six years after the initial description of the acquired immunodeficiency syndrome, much has been learned about the etiologic agent, the human immunodeficiency virus. The pathogenic mechanisms utilized by this virus to infect selectively and persistently T4+ lymphocytes and monocyte/macrophages, leading to immunodeficiency and neurologic dysfunction, are slowly becoming clear. Better understanding of the pathogenesis of human immunodeficiency virus infection is essential for the rational design of therapeutic and preventive strategies to combat this deadly virus. PMID- 3324513 TI - [The epidemiology of Christoph Wilhelm Hufeland (1762-1836). A contribution to the history of pre-bacteriologic epidemiology]. PMID- 3324514 TI - [Pathogen colonization in the infected root canal]. PMID- 3324515 TI - [New knowledge of the structure and action of animal cell growth and hematopoiesis-regulating factors]. AB - A survey is given of several new growth factors from tissues of animals, in particular of the endothelia cell growth factor (= heparin-binding growth factors), the multipotent growth factors from brain of cattle, the prostatropins as well as the growth factors for fibroblasts and glia-cells. Several more recent recognitions on the importance of the insulinlike growth factors, the tumour growth factors and the chalones are described. For the regulation of the haemotopoiesis the factor furthering the formation of multicolonies (= pluripoetin, interleukin 3), the factor furthering the formation of erythrocyte macrophages colonies, the factor furthering the formation of macrophage-colonies and the erythropoietin are of importance. PMID- 3324516 TI - [Berolina iubilans: Berlin physicians as Halle doctoral candidates (IV). Johann Ulrich Bilguer (1720-1796), Halle doctoral candidate of 1761]. AB - The physician Johann Ulrich Bilguer (1720-1796) born in Chur in Graubunden obtained high posts in military medicine in Prussian services. He had particular merits in the organization of military hospitals. With his doctoral thesis on indication and contraindication of amputations submitted in Halle in 1761 he became the "Father of the conservative surgery" as he was called. During his stay in Berlin for many years Bilguer wrote a number of treatises, in which he expressed his opinion to many medical scientific problems and again to questions of an improved treatment of patients. PMID- 3324517 TI - [Recent knowledge of the biochemical significance of proto-oncogenes, their activation and development of tumors]. AB - In each cytoblast of mammals about 30 protooncogenes are present which during the embryonic, the fetal and the postnatal development, respectively, in certain cell types may temporarily or permanently be used for the formation of certain proteins. A part of these proteins is of importance for the furthering of the division (DNA-replication) and the differentiation of the cells. According to the qualities in the proteins formed by protooncogenes the protein kinases, the GTP binding proteins and the DNA binding proteins are differentiated. Under the influence of carcinogens and of cocarcinogens several protooncogenes are changed in their structure and displaced, respectively, within certain chromosomes. Thus they are transduced into oncogenes and evoke an increased formation of transforming proteins which initiate a dysregulation of the transcription in the nucleus. Several aspects of the activation of protooncogenes, of the development of tumours as well as of the origination of tumours by recessive mutation are described. PMID- 3324518 TI - [Berolina iubilans: Berlin physicians as Halle doctoral candidates (V). Marcus Herz (1747-1803) and Berlin Jewish physicians]. AB - A number of Jewish medical students from Berlin went in for the formalities for taking a doctor's degree at Halle university in the 18th century. Among them there were several physician-personalities whose names are held in high esteem in the history of medicine up to now. In particular Marcus Herz who graduated in Halle in 1774 came into prominence by outstanding achievements in teaching and research. Under his management at that time a whole generation of Jewish medical students in the Jewish hospital found the occasion to a practice-relevant preacademic education. PMID- 3324519 TI - [Rate of complications in acute treatment of stomach ulcer: modification of the incidence by active therapy in placebo-controlled studies]. AB - We evaluated 32 randomized placebo-controlled trials in gastric ulcer patients to determine the ulcer-related complication rate (bleeding, perforation) during short-term therapy. Patients treated with placebo had a significantly greater risk to drop out for ulcer-related complications than patients treated with active drugs (1,2% vs 0%; p less than 0,01), while the number of patients dropping out for other reasons did not differ significantly (8,4% vs 7,3%, p greater than 0,1). Thus, the efficiency of active drug therapy in gastric ulcer episodes is not only reflected by a significantly higher healing rate in 4 to 8 weeks (64,7% vs 41,4%, p less than 0,01) but also by a much lower risk for ulcer related complications. PMID- 3324520 TI - [Lithogenicity and bile acid pattern in choleretic administration (3-n-butoxy-1 phenoxy-propanol: febuprol) in patients with functional right upper quadrant pain]. AB - 10 patients with right upper quadrant pain were treated with a choleretic agent (Febuprol; 3 X 200 mg t. i. d.) and placebo in a cross-over double dummy technique for 16 weeks. Lithogenic index, bile acid profile and serum lipids were determined every 4 weeks. During Febuprol application the clinical symptoms were relieved (0.87 +/- 1.3 vs. 1.39 +/- 0.21 (placebo); p less than 0.05, semiquantitative score). Biliary lithogenicity (1.45 +/- 0.6 vs. 1.09 +/- 0.12; n. s.), bile acid profile and serum lipids showed no statistically significant change, although serum cholesterol levels seemed to fall during Febuprol application. PMID- 3324521 TI - [Changes in uterine circulation in relation to body position in pregnancy]. AB - The present paper reports on studies to determine the influence of body position on uterine blood flow. In ten pregnant patients (around the 35th week of gestation), over 700 measurements of systolic/diastolic action in the uterine vessels were made by Doppler sonography with the patients in various positions: lying down, standing, and sitting on the couch and the balance-variable chair; from the relationship between the systolic and diastolic levels conclusions were then drawn about the uterine blood flow in various body positions. It was found that it was best when the patient was lying down or sitting on the special chair without angling the hips; in contrast, diastole was lower in relation to systole with the patient standing and sitting on the examination couch. This means an increase in resistance or a reduction in blood flow. It appears reasonable to conclude that sitting on the balance-variable chair can be recommended to pregnant patients with signs of deficient fetal blood supply, in addition to bedrest, which is customarily advised. Apart from this, it is wise to use Doppler sonography to establish the body position in which uterine blood flow is best. PMID- 3324522 TI - [Significance of Doppler blood flow studies in twin pregnancies]. AB - Twin pregnancies are characterized by similar uteroplacental but different fetoplacental haemodynamics at the same gestational age. The aim of this study was to investigate the correlation between Doppler blood flow measurements of fetal vessels and the morphological findings of the placenta, fetal growth and signs of fetal hypoxia. The study group consists of 18 twin pregnancies with operative delivery. In all cases the placenta was examined morphologically. We found similar discordancies in the pulsatility index (PI) or the mean blood flow velocity (Vmean) of the fetal aorta (measurements less than 7 days before delivery) and the birth-weight. In twin pregnancies with operative delivery due to fetal indication in 11 out of 12 cases the twin with suspected hypoxia had a relatively lower Vmean and a higher PI value. The association of pathological blood flow velocity waveforms of the umbilical artery, the fetal aorta and the fetal common carotid artery and histomorphological findings of the placenta could be demonstrated. PMID- 3324523 TI - [Amoxicillin in the treatment of asymptomatic bacteriuria in pregnancy--3g single dose versus 3 times 750mg 4-day therapy]. AB - A prospective, randomized, controlled comparative clinical trial was conducted to assess the efficacy and tolerability of 2 regimens of amoxicillin. In group A a single dose of 3 g amoxicillin and in group B a 4-day course of 3 doses of 750 mg amoxicillin tablets were administered 8-hourly. Significant bacteriuria (greater than or equal to 10(5) cfu/ml midstream urine) and of urine samples obtained by bladder catheterization (greater than or equal to 10(4) cfu/ml) was diagnosed with the dip-slide method (Uricult). 91 pregnant women with a mean gestational age of 25 weeks (14-38) were randomly allocated to both treatment groups. Group A consisted of 53 patients, group B of 38. The treatment groups were comparable in terms of age, duration of pregnancy and additional therapy. Control examinations of urine cultures were taken after 1 and 4 weeks following therapy. The predominant bacterial species was E. coli isolated in 60 to 65 percent. Bacteriological cure rates at 1 and 4 weeks were in group A 77% and 74% and in group B 62% each respectively. The differences in cure rates were not significant. Side effects occurred in group A in 4% and in group B in 13%. Our results suggest that for the treatment of asymptomatic bacteriuria in pregnancy a single dose of 3 g of amoxicillin is equally effective and acceptable as a 4-day course with the advantage of a lower total-dose, lower costs and a better compliance. PMID- 3324524 TI - [Persistent pulmonary hypertension of the newborn infant (PPHN)]. AB - Persistent pulmonary hypertension of newborn (PPHN) is due to a defect in the adaptation of pulmonary resistance. The primary form occurs idiopathically, with meconium aspiration syndrome and with hypoplasia of the lung and is characterised by excessive muscular hyperplasia of pulmonary arteries. Secondary PPHN following hypoxia, septicaemia and shock is due to pulmonary vasoconstriction whereby thromboxane, leukotrienes and prostaglandins play a decisive role. Diseases of the pulmonary parenchyma and congenital cardiac malformations have to be excluded. The increased pulmonary resistance can be demonstrated by two dimensional cardiography. The therapy consists of hyperventilation and tolazoline, which can be complicated by severe side-effects. High frequency oscillation and jet-ventilation are employed experimentally, Extracorporeal Membranoxygenation is a promising new method. PMID- 3324525 TI - [Comparative immunofluorescence study of actinic keratosis and chronic discoid lupus erythematosus]. AB - Regarding systemic (SLE) and chronic discoid lupus erythematosus (CDLE), the diagnostic value of the lupus band test ist generally accepted. In the literature, however, there are but few obligatory criteria concerning the definition of a positive lupus band. In order to illustrate the influence of sunlight on the evolution of junctional deposits of immunoglobulins, we examplarily studied actinic keratosis (AK) as a chronic light-dependent dermatosis. The junctional deposits in AK were qualitatively and quantitatively compared with the lupus band typical for CDLE. In CDLE we mostly found more distinct band-like junctional deposits of immunoglobulins and complements. Light dependent, non-specific junctional patterns of immunofluorescence similar to LE, therefore, require clear morphological criteria of immunohistology. PMID- 3324526 TI - Long-term treatment of hypertrophic cardiomyopathy with verapamil or propranolol in matched pairs of patients: results of a multicenter study. AB - The effects of a 2-year treatment with high-dose propranolol (mean, 340 +/- 135 mg/day) and verapamil (mean, 493 +/- 136 mg/day) were compared in two groups of patients with hypertrophic cardiomyopathy. Both groups were broadly identical at the beginning of the trial and were formed of matched pairs. Out of 137 patients entering the study, 37 pairs completed the 2 year follow-up. The mean group symptomatology (NYHA-classification) improved significantly only following verapamil treatment. Individual improvement was seen more often following verapamil (V), but deterioration was almost exclusively seen during propranolol (P) treatment. Reduction of the Sokolow-index was significant in the V group only. Reduction in the resting heart rate and maximum gradient was more pronounced following P. No correlation could be found between the change in clinical symptoms and electrocardiographic, echocardiographic or hemodynamic data, nor to the dosage of V or P administered. From clinical and echocardiographic findings and in respect of side effects, V is advantageous over P in the treatment of hypertrophic cardiomyopathy, although a considerable number of patients improve after P. Objective data do not allow one to anticipate responders or non-responders to either treatment. PMID- 3324527 TI - Dynamic obstruction to left ventricular outflow: the case for its existence in hypertrophic cardiomyopathy. AB - The debate and controversy over the hemodynamics of obstruction and left ventricular ejection in HCM is an interesting and complex one in which periodic disagreement has appeared during the last 20 years. We believe that the available data unequivocally support the concept that in those patients with HCM who have left ventricular outflow gradients measured at catheterization (and who have associated marked SAM) a mechanical impediment to forward flow, and thus true obstruction to left ventricular outflow, does exist. Most importantly, the gradient has critical clinical implications by virtue of the markedly elevated intraventricular systolic pressures associated with it. These chronically elevated pressures are potentially detrimental to the left ventricle (a view held even by investigators opposed to the term "obstruction"), by virtue of increasing systolic myocardial wall stress and myocardial oxygen demand. Therefore, surgical abolition of the obstruction and normalization of these pressures remains an important and rational therapeutic objective in those severely symptomatic patients who have obstruction to left ventricular outflow and who have failed to benefit from drug therapy. PMID- 3324529 TI - Transport and function of L-carnitine and L-propionylcarnitine: relevance to some cardiomyopathies and cardiac ischemia. AB - Carnitine, an essential cofactor in fatty acid oxidation, plays a central role in myocardial metabolism. Interpretation of the biochemical features of disturbed myocardial function, particularly in ischemia, may be facilitated by understanding carnitine biosynthesis, transport and function. Biosynthesis: In man, deoxycarnitine, the immediate precursor of carnitine, is synthesized in all tissues, whereas the last step, the conversion of deoxycarnitine into carnitine may only take place in liver, kidney and brain (Figs. 1 and 2). Deoxycarnitine formed by organs like muscle or heart is released into the plasma, taken up by liver and kidney, converted into carnitine which is secreted into the bloodstream to be taken up by heart or muscle (Fig. 2). Carnitine transport and cellular function: The myocardial uptake of carnitine against a large concentration gradient (Table 1) occurs in an 1:1 exchange-diffusion process. Under physiological conditions, intracellular deoxycarnitine is exported and extracellular carnitine is imported. According to this model, myocardial carnitine deficiency may be due either to a functional alteration of the sarcolemmal carnitine carrier or to a deficient synthesis of deoxycarnitine. D carnitine, acetylcarnitine and long-chain acylcarnitine esters are also transported by the carrier at different rates. This might account for the release of endogenous acylcarnitines accumulated in anoxic or ischemic conditions, contributing to the cardioprotective effect of carnitine by reduction in intracellular long-chain acyl-coenzyme A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324528 TI - [Carnitine metabolism--changes in the end stage of dilated cardiomyopathy and ischemic heart muscle disease]. AB - Biochemical analyses from endomyocardial biopsies indicate that cardiac energy metabolism is altered in patients with end-stage cardiac failure. Myocardial energy production is predominantly based on fatty acid oxidation. Carnitine, a naturally occurring compound, plays an essential role in fatty acid oxidation by carrying long-chain fatty acids into the mitochondrial matrix where they undergo beta-oxidation. In experimental animals, myocardial carnitine deficiency may cause cardiomyopathies which are reversible with carnitine substitution. Rare human diseases, as systemic carnitine deficiency, are associated with impaired cardiac function. We therefore investigated carnitine metabolism in patients with cardiac failure. Plasma and myocardial carnitine levels were measured in 55 patients undergoing cardiac transplantation because of end-stage cardiac failure based on dilated cardiomyopathy (DC, n = 30) or coronary artery disease (CAD, n = 22). Elevated plasma carnitine levels (controls: 49 +/- 12 microM; DC: 82 +/- 38 microM; p less than 0.001, CAD: 86.9 +/- 21.6 microM; p less than 0.05) were found in both patient groups (Fig. 1). Plasma carnitine did not correlate with creatinine (Fig. 2). Compared to controls, myocardial carnitine levels were significantly reduced: DC: 5.9 +/- 1.45 nmol/mg NCP; CAD: 5.84 +/- 1.84 nmol/mg NCP; controls: 15.6 +/- 5.4 nmol/mg NCP (Fig. 3). No correlation between myocardial and plasma levels was found (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324530 TI - Role of carnitine-dependent metabolic pathways in heart disease without primary ischemia. AB - 1. Carnitine and carnitine palmitoyltransferase are active in the transfer of fatty acids into the mitochondria for oxidation. Very long chain fatty acids (C22) are poorly oxidized by mitochondria. Lack of carnitine or overloading with C22 fatty acids leads to lipidosis in heart and other tissues. 2. The oxidation of fatty acids (including C22 fatty acids) in the peroxisomes is not dependent on carnitine. However, carnitine acetyltransferase and carnitine medium chain acyltransferase are presumably auxiliary enzymes in the oxidation of acetyl-CoA and shortened fatty acids formed in the peroxisomes. 3. Branched-chain acylcarnitines may be formed in the mitochondria from branched-chain amino acids. They are also metabolized in the mitochondria. When formed in large amounts, they are released into the circulation and urine by the liver and kidney. 4. The mechanisms leading to secondary carnitine deficiency because of branched-chain acylcarnitine formation in metabolic disturbances are discussed. PMID- 3324531 TI - Effect of insulin on adrenal medulla in two avian species. PMID- 3324532 TI - Cytochemical investigation of plasma membrane bound enzymes in the cerebellar cortex of the Mongolian gerbil (Meriones unguiculatus). PMID- 3324533 TI - [Management of long-standing instabilities of the knee ligaments]. AB - Since 1975, a total of 1015 knee ligament grafts have been carried out in the orthopedic department of the St. Elisabeth-Klinik in Saarlouis. Proceeding from the method of extra-articular stabilization that was taken over and modified by Mittelmeier, the authors initially favored Ellison's method of lateral ligament displacement, supplementing the operation by diverting the nerve tract. Although the results of surgery were not bad, the importance of rotational instability led the authors increasingly to turn to intra-articular stabilization. Today, the most commonly used methods for frontal instability are those modified by Bruckner or Glency, both with good results. With regard to ligament prostheses, the authors tend to be more cautious. Certainly, the alloplastic artificial ligament replacement is an important advance in the case of certain indications, but is probably only a further element of future developments. Many of the problems encountered by Fritz Lange with his first, silk plastic ligament replacement, described by Max Lange in the 1960s, are still applicable today. Here one could mention in particular the surgeon's misgivings concerning indication and the cautious estimates of the changes of success of plastic surgery of the ligaments. PMID- 3324534 TI - [Experiences with the Mittelmeier ceramic screw acetabulum in exchange operations for loose endoprostheses]. AB - This is a report about our experience with the replacement of loosened acetabular endosprotheses by the self locking ceramic Endoprosthesis Mittelmeier. That's an analysis of 60 patients concerning age, sex incidence, indications, primary implant type and long term findings. The clinical findings are illustrated according to the schedule of Merle d' Aubigne. The critical evaluation shows, that the self locking ceramic cup allows the additional implantation of homologous or autologous bone chips and grafts avoiding further allogenous implants. PMID- 3324535 TI - [Sonographic follow-up of hip dysplasia treated with an abduction brace]. AB - 121 children with cdh, which haven been treated between June 84 and December 85 in our out-patient-ward with Aktivspreizhose (abduction-pants), have been followed by ultrasound examination. Reliability of hip ultrasonography, duration of treatment and results have been evaluated. At the beginning of treatment the diagnosis were: 24.8% type IIa, 29.6% type IIb, 13.2% type IIG or IID and 5.8% type IIIa according to Graf; in 6.6% of the cases cdh was diagnosed only by x rays. Hip ultrasonography was highly reliable according to quality controls in comparison to x-rays and short-ended the duration of treatment. With the exception of 3 children (1 Myelodysplasia, 2 start of treatment after the 6 months of life) all children with "Aktivspreizhose" treatment showed anatomic healing. Duration of treatment was 4.2 months on the average, 3.5 months when treatment started in the first 3 months of life, and 4.7 months, when started after the first 3 months of life. X-ray-controls at the end of treatment showed mild forms of femoral head necrosis (type I and II) in two cases, which healed completely according to follow up controls. For the treatment of cdh in babies the Aktivspreizhose is the optimal therapy, especially when started in the first 3 months of life. A general legal orthopaedic clinical and ultrasound screening of babies hip in the first week of life should be introduced. PMID- 3324536 TI - Immunoglobulin therapy for HIV-associated thrombocytopenia. PMID- 3324537 TI - [On the 80th anniversary of the birth of Academician Mikhail Nikolaevich Livanov (1907-1986)]. PMID- 3324538 TI - [Spatial synchronization of the cortical potentials and high-frequency components of neocortical electrical activity during learning]. PMID- 3324539 TI - [Passive smoking. Acute effects on the lung function of sensitive persons]. AB - From the relationship between the degree of air pollution due to tobacco and its acute effects on healthy persons it is possible to estimate the still tolerable level of air pollution for healthy adults. The results and conclusions of the studies published by now on acute effects of passive smoking on patients with bronchial asthma are partially contradictory and do not allow a reliable estimation of the upper limit of tobacco smoke exposure for this particularly sensitive group. Because of methodological problems in studies with symptomatic asthmatics, further studies should be conducted which investigate patients with hayfever and asthma out of the pollen season, clinically healthy subjects with nonspecific bronchial hyperreactivity upon pharmacological challenge, and subjects who claim sensitivity to tobacco smoke. PMID- 3324540 TI - Medical and social service provision for families of children with NTD. AB - The supply of services to the families of children with spina bifida participating in the South Wales longitudinal study was reviewed. Initially general information and contact with other mothers were the commonest needs; as the children grew older the need for practical, material and financial help took priority. Parents were, generally, very satisfied with support provided by hospital staff with whom they had frequent, regular contact. Contact with health visitors and social workers was considered insufficient and unsatisfactory. Mothers of more severely disabled children were most likely to receive visits, but some saw none and contact with the social services decreased as the children got older. The locally organised parents association (SWASBAH) was able to provide information, financial assistance, holiday accommodation, and contact with others in a similar position; all of which were common, but otherwise inadequately met, needs. Despite improvements, particularly in financial benefits, over the course of the study, at 18 years parents appeared largely unsupported as they faced major changes in their children's lives. Throughout the study support from SWASBAH and the interviewer appeared to far outweight the statutory, non-medical, support. PMID- 3324541 TI - Simple help for spina bifida children with anal incontinence. AB - The search for an effective means of helping children with anal incontinence has been facilitated by tissue-compatible material which has already been in use for a long time in proctology. Polyvinyl alcohol foam is characterized by its elasticity, malleability under the influence of liquids and its good tissue compatibility. We have had anal plugs manufactured in the shape of hourglasses. These are available in various sizes and can be adapted individually. We consider their application to be indicated in about one third of myelomeningocele children who either have partial or complete fecal incontinence. We have also tested the plugs in healthy children and experience is available in the meantime in eight children after operation on a high anal atresia and 15 children with spina bifida. The period of application is in childhood. Our experience so far is encouraging. The handling is described in detail. PMID- 3324542 TI - The outcome of pregnancies diagnosed as having a fetus with meningomyelocele. AB - Forty-nine cases of meningomyelocele diagnosed in utero and another 10 cases delivered by prelabor cesarean section (N = 59) are compared to all other cases of meningomyelocele (N = 98) born following labor and seen during the same period. Prenatal diagnosis was established for 19 cases before and 30 cases after 24 weeks gestational age. Ten cases were delivered by prelabor cesarean section for maternal indications. Eight of 12 cases diagnosed before 24 weeks and given a guarded prognosis and one given a poor prognosis, elected cesarean section. One of the 8 was stillborn. Four of the 12 given a guarded prognosis and 6 an extremely poor prognoses elected termination of the pregnancy. Nineteen of the 30 cases diagnosed after 24 weeks were delivered by prelabor cesarean section and two by cesarean section after inadvertent labor. Of the 35 cases born by prelabor cesarean section, 48% have sacral levels or no loss of motor function compared to 14% of the 98 born after labor (P = 0.0001). We recommend prelabor cesarean section before onset of labor to preserve neural function of a baby with meningomyelocele and leg movement in utero when parents refuse termination or have a diagnosis made after 24 weeks gestational age. PMID- 3324543 TI - The route learning ability of young people with spina bifida and hydrocephalus and their able-bodied peers. AB - The ability to find our way about in the environment is taken for granted by older children and adults, the majority of whom find no major difficulties with this task. It is generally accepted that the ability to mentally "map" our environment is developmental, conceptual understanding of space being based upon accurate perceptions. It might therefore be expected that perceptual deficit could affect the ability to form cognitive maps and lead to way finding difficulties. This paper investigates the "cognitive mapping" ability of 9 young adults disabled by spina bifida and hydrocephalus and their able-bodied controls. All Ss were clinically assessed for nonverbal reasoning ability, spatial ability, left-right orientation and memory skills. Each person was driven along two routes, route learning being assessed by (a) directing a driver along the routes (b) marking the routes on sketch maps and (c) drawing freehand sketch maps of the routes. Results indicated that although the able-bodied groups performed better on reasoning and spatial tests, general reasoning ability and mobility experiences were more important than level of perceptual skill alone for route learning in a real life situation. The importance of environmental experiences and independence training for mobility during childhood for those with spina bifida and hydrocephalus is stressed. PMID- 3324544 TI - Magnetic resonance imaging in children suffering from spina bifida. AB - 22 children with myelomeningocele (MMC) were examined by magnetic resonance imaging (MRI). After operative closure a tethered cord was found in 78% of the patients. A primary tethered cord was detected in all patients where a lipomyelomeningocele had not been operated on yet. Additional malformations shown by MRI were hydromyelia and diastematomyelia. No correlation could be found between the degree of morphologic changes and the clinical course. In covered MMCs, MRI investigation is recommended as method of choice before operation. After operative closure a control-MRI should be performed after three months. If there are no pathological findings, further follow-up should be done by ultrasound investigation twice a year. PMID- 3324545 TI - [Current issues in medical liability]. AB - Currently, liability discussions are being dominated by AIDS and the legal problems associated with birth and death. The introduction of routine AIDS tests without the knowledge of those concerned is disputed heatedly and, in fact, may well constitute bodily assault and render those responsible liable to prosecution. In AIDS cases, the apparent breach of the Hippocratic oath of secrecy by Physicians can be justified on the grounds of both the extraordinary circumstances prevailing and conflicting duties. The transmission of AIDS could give rise to prosecution for causing bodily injury or manslaughter. The drawing up of a law to protect embryos is designed to establish legal constraints in the fields of reproduction and gene technology. In reframing section 168 StGB, which provides protection to the dead embryo, legislators assume that the head of a medical clinic is the lawful custodian of the corpse of a person who has died in his institution. This should help to resolve many of the problems arising from post-mortem examinations. The questions of euthanasia and medical assistance in cases of suicide were raised at the 1986 Conference of German Lawyers. Whereas medical treatment that could be considered as interference with the natural process of dying may be withdrawn in the case of irreversible terminal suffering, active euthanasia, i.e. the deliberate killing of a terminal patient, was rejected. With regard to noninterference in a suicide attempt by a third party, the free decision of the person wishing to commit suicide should be respected. In general, however, the maxim in dubio pro vita should be respected and where any doubt exists, an attempt should be made to save the person's life. PMID- 3324546 TI - [Historical retrospect of psychotherapy guidelines]. PMID- 3324547 TI - [Myocardial infarct. (II). Personality pattern and experience]. AB - Coronary disease of different degrees of severity, from short-term angina pectoris to the lethal infarction, is both a result and an expression of certain types of experiences and conflicts in people with a particular personality structure. These people are characterized by a strong drive toward and high degree of activity, by ambition and an aggressive stance. The situation in which coronary disease appears is marked by occupational stress and excessive demands, by lack of satisfaction, lack of success, and a drive toward social subordination; familial problems of the same kind and the loss of someone to whom a person has close ties can also have pathogenic effects. The explanation for the relationship between coronary morbidity and mortality in a social collective lies in particular personality structures and the specific conflict situation. PMID- 3324548 TI - [Inpatient psychotherapy in West Germany. Sociocultural determinants, developmental stages and current status, international comparison]. AB - In the Federal Republic of Germany, stationary psychotherapeutic treatment of the psychogenically ill in independent institutions has undergone and expansion without international parallel in the last few decades. This development is based on a number of particular sociocultural circumstances that have combined to exercise optimal influence. A review of the situation--it is estimated that there are ca. 5,000 beds for psychotherapeutic cases--and an international survey supplement the analysis of an area of care that has developed parallel to out patient psychotherapy. PMID- 3324550 TI - [Our urologic heritage: Carl Posner (1854-1928)]. AB - We remember the Berlin urologist Carl Posner (1854-1928) who by his scientific urological work as well as by his activities as an editor has greatly furthered the development of urology to a scientific subject. After the description of his life particularly his political work in associations is treated, which made him the organizer of the international medical associations in the first half of the 20th century. PMID- 3324549 TI - [Value of antibacterial therapy in chronic obstructive urinary tract infections]. AB - On the basis of a clinical study an analysis about 86 patients with obstructing bilateral nephrolithiasis and chronic obstructive infection of the urinary tract is elaborated. In order to illustrate the change of resistance of the causative agents during a period of 10 years (1973-1982) two separated 5-year analyses are compared. It is made evident that the relations of sensitivity to seven chemotherapeutic drugs in Coli, Proteus and Pseudomonas infections have changed in favour of increasing resistances of causative agents. The results obtained are an expression of the unstableness of antibiotic therapies under palliative purpose when urological basic diseases are not removed. From the analysis the demand for changing the general problems of obstructive pyelonephritis without possible operative sanation becomes evident. early diagnosis and treatment of predisposing factors are the two keystones of our efforts, when the chronic obstructive infection of the urinary tract by resistant causative agents shall not remain a therapeutic problem in the same measure as hitherto. PMID- 3324551 TI - Influence of the antibiotics roxithromycin and erythromycin on the gastro intestinal ecology of mice. PMID- 3324552 TI - [Histogenesis, degeneration, regeneration and adaptation, aging and compensation in the skeletal muscles]. AB - The concept of multicellular histogenesis of skeletal muscle fibre is the basis for understanding embryonal genesis of the voluntary muscles as well as muscle fibre regeneration. Formation and maintenance of the neuromuscular units are preconditions for function. Embryonic development and histogenesis regeneration are described. Changes resulting from metabolic defects, trauma, neurogenic and muscular disease are contrasted. Changes in nerves and synaptic junctions due to degeneration and regeneration are illustrated. Alteration in fibre type composition and muscle fibre diameter are regarded as the principle form of muscle adaptation to a changed loads. A central nervous system mechanism influencing fibre type and a peripheral humoral mechanism influencing the magnitude of peripheral motor units are postulated. The role of intramuscular sprouting is underlined. The structurally recognizable correlates of aging, such as decreased fibre diameter, increasing fibre type grouping and reduction of the total number of muscles fibres should be viewed as physiological phenomena. Sensomotor regulation of compensatory mechanism of muscular activity including fibre type grouping, compensatory hypertrophy, target fibres and ring fibres results in distinctive patterns under etiologically distinct pathological conditions. PMID- 3324553 TI - [The question of IgE activity in the mucosa of the large intestine]. AB - The importance of the IgE mediated inflammatory process of the large bowel mucosa was investigated by examining rectal biopsies using the peroxidase-antiperoxidase method in 172 patients to demonstrate IgE cells in the inflammatory infiltrate. IgE-positive cells could be demonstrated in small numbers in all specimens. The numeration of the plasma cells in the inflammatory infiltrate showed in most cases between 1 and 3% positive cells, only in four specimens between 5 and 6% and in two over 10%. The four groups of the specimen biopsied showed no difference in the frequency of IgE cells. The larger number of such cells in colitis ulcerosa should be viewed as the result of the more intense inflammatory process in the specimen. There was no difference either in the frequencies of mast cells in the mucosa. The findings of this investigation do not support a causative role of IgE mediated processes, in particular of the chronic inflammatory bowel disease. PMID- 3324554 TI - [Pathological anatomy--past, present and future]. AB - Beginning with a brief overview of its history the future developments of pathologic anatomy are anticipated. While the major tasks of the institutes of pathology in hospitals lie in clinical pathology, the emphasis of the university institutes is on teaching and communicating the basis of general pathology and pathological anatomy. Progress requires a more intensive development of experimental and theoretical research as well as new morphologic techniques, taking advantage of recent scientific and technical advances. Clinical pathology should not be among the primary goals of university institutes. One of their major tasks must be the elaboration of cognitive theoretical concepts to further develop the understanding and classification of diseases and neoplasias, and their complex etiologies. The relationship with other medical disciplines is discussed. Pathological anatomy at universities should reflect the spirit of Virchow's pathology as is obvious from its history and traditions. PMID- 3324555 TI - [Adjuvant chemotherapy in cancer surgery]. AB - Isolated surgical approaches to tumor treatment have largely reached a point beyond which prospects appear to be unpromising. The search for more promising therapeutic approaches, therefore, has become a compelling challenge. Surgico adjuvant tumour chemotherapy has been more thoroughly studied than anything else in that direction. The underlying theoretical concept seems to be persuasive, though clinical results have so far stayed below expectations. Secured prolongation of life, following this therapy, has so far proved to be probable only for cases of osteosarcoma, mammary carcinoma with high risk of recurrence, testicular tumours, and neurogenic tumours. Neo-adjuvant chemotherapy seems to work well in cases of ENT tumours. Model studies into Lewis-Lung carcinoma have shown that therapeutic effects cannot be guaranteed unless a sensitised tumour is treated with an effective preparation. This is likely to add to the long-range importance of the individual aspects relating to surgico-adjuvant tumour chemotherapy. Methods have been and continue to be developed for that purpose. Yet, all of them need to be methodologically improved. At present, waiting for such improvement, surgico-adjuvant tumour chemotherapy should be used only within the framework of controlled clinical studies. PMID- 3324556 TI - [Problems of antineoplastic chemotherapy of pancreatic cancer]. AB - Antineoplastic chemotherapy of pancreas carcinoma remains to be an area of intensive research. There are no convincing suggestions for far as to clinical superiority of polychemotherapy. However, combined methods seem to improve survival in cases of both advanced and surgically removed pancreas carcinoma. New, effective pharmaceuticals should be looked for in the foreseeable future. Interdisciplinary approaches will continue to be of great importance. PMID- 3324557 TI - [Combination therapy of malignant melanoma]. AB - Primary treatment of malignant melanoma should be surgical, with due consideration being given to certain peculiarities, including safety distance and radical lymphonodectomy in cases of lymph node metastasation. Adjuvant chemotherapeutic measures have failed to meet expectations in terms of adjuvant or palliative effects on healing. They have simply proved to prolong life with tumour presence. PMID- 3324558 TI - [Our surgical heritage. Contemporary documents and works of art. The painting, "The Founders of the German Society of Surgery" by Ismael Gentz]. PMID- 3324559 TI - [Possibilities and significance of using lasers in gynecology]. AB - Since 1973 laser technology has found its way into gynecology as well as other branches of medicine. CO2-, Neodym-YAG-, and argon-laser have been used. Experience has been made with the laser treatment of benign and precancerous lesions of the vulva, vagina, and cervix uteri. The laser is also being used increasingly for infertility operations, adhesiolysis and treatment of endometriosis. Since 1979, the laser has also been applied pelviscopically for these indications. As an advantage of laser techniques the possibility of operating atraumatically and relatively bloodlessly has been named. Disadvantages have been found in the high cost of the equipment, the special training required of the physician, and the possible danger for the patient and the operation theatre staff. Until now, there has been no definite proof that laser technology gives better results in the various operations mentioned than conventional methods. PMID- 3324560 TI - [Incidence of B streptococci in gynecologic patients, pregnant patients and newborn infants]. AB - 821 patients have been examined with regard to the presence of B streptococci. We isolated B streptococci in 5.4 per cent in gynaecologic outpatients, in 0.4 per cent in 236 pregnant women and in 5.8 per cent in 156 newborns. From 78 to these newborns we were able to examine the mothers during their stay in the delivery room, too. Only in one parturient and her newborn we could detect B streptococci. In three B streptococci positive newborns is was not possible to prove this germ in the vaginal content of their mothers. Clinical symptoms were not present in no case. Antibiograms were not peculiar. PMID- 3324561 TI - [Postcoital contraception with dienogest]. AB - Fifty eight fertile female volunteers between 20 to 45 years were enrolled in a clinical trial to evaluate the efficacy and tolerance of the progestin dienogest (17 alpha-cyanomethyl-17 beta-hydroxyestra-4,9-dien-3-one, VEB Jenapharm Jena GDR) as a postcoital contraceptive. An oral dose of 2 mg dienogest was administered immediately after each coitus. The 58 women reported 872 intercourses during 302 cycles. Frequency of ingestion was on average 3 times per cycle. Pregnancy occurred in 14 women corresponding to a Pearl-index of 55.6. The observed pregnancy rate referring to all intercourses was 1.6 per cent. The incidence of expected pregnancies in relation to the coital exposures was 4.04 per cent. As a result the risk of pregnancy was reduced 2.5 times by dienogest. Menstrual disorders occurred in 18.9 per cent in regard of the total numbers of cycles. The results and an overview of literature suggest that neither dienogest nor other progestins are suitable as a sole contraceptive method when used as a postcoital agent. They are only indicated as a risk-reducing method after so called "contraceptive emergencies". PMID- 3324562 TI - [Status of ultrasound and roentgen diagnosis in prenatal detection of osteochondrodysplasias]. AB - Ultrasound and X-ray investigation have a specific but complementary importance within the prenatal recording of lethal osteochondrodysplasia. In the prenatal diagnoses of thanatophoric dysplasia, asphyxiating thoracic dysplasia, chondrodysplasia punctata and achondroplasia we present our procedure for the investigation. All pregnant women are examined by ultrasound. Where the sonographical findings--according to our previous definition for the above mentioned diseases--suggest that they may be present we recommend referral to an institution with highly-specialized diagnostic possibilities for further investigation. Already in the II. trimester of pregnancy it is possible to make such group diagnoses by ultrasound. To give further specificity to the findings prenatal X-ray investigation should be done preferably in the III. trimester. The importance of confirming the diagnosis by either postnatal or postmortem X-ray investigation should be emphasized. PMID- 3324564 TI - [Intrapartum sonographic study in clinical suspicion of cephalopelvic disproportion]. AB - The realisation of a clinical disproportion is--still nowadays--a high demand for obstetricians. The ultrasonic examination of pelvis represents an intermediate stage between clinical and radiological examination. Description of pelvis by measuring the true conjugate and intrapartal diagnosis of abnormalities of adjustment and bearing of the fetus. It enables in many cases to set the indication of caesarean section earlier and safer. PMID- 3324563 TI - [Tocolysis with clenbuterol tablets]. AB - The authors report on the results of treatment of threatening premature labour with clenbuterol. The daily dose was 40 micrograms twice and later 20 micrograms twice with good efficiency. Action of clenbuterol relating to tocolysis, metabolism and cardiovascular system has been compared with fenoterol perlongettes. 61 pregnant patients were randomized by computer in two groups, 32 ones having clenbuterol tablets and 29 ones having fenoterol perlongettes. No electrocardiographic changes could be demonstrated with clenbuterol, but extrasystolic episodes have to be observed in two following fenoterol perlongettes. No intravenous treatment is necessary using clenbuterol tablets. Therefore cardiac overload caused by liquid supply may be prevented, simultaneously the peril of pulmonary edema can be diminished. In our opinion tocolysis with clenbuterol tablets is a successful method of treatment of premature labor. PMID- 3324565 TI - Epidemiology (1980-1985) and nonspecific prophylaxis of Q fever in the USSR (survey). AB - A review of the epidemiology and nonspecific prophylaxis of Q fever in the USSR during 1980-1985 is presented. Attention is paid of the source to infection, the seroprevalence of antibodies to Coxiella burnetii in man and livestock and the possibilities of prophylaxis against Q fever under conditions of mandatory registration of this disease. PMID- 3324566 TI - Epidemiology and significance of Q fever in Czechoslovakia. AB - Over the last 35 years most parts of Czechoslovakia have experienced Q fever. Of particular note were outbreaks in factories processing imported cotton, wool and hides that had been contaminated in their countries of origin. Some areas of the southern part of Central Slovakia became a natural focus of Q fever with the Dermacentor marginatus tick being the main vector of coxiellae. Currently, Coxiella (C.) burnetii infection appears to be dormant in the country since only sporadic cases are encountered. Cattle vaccination practiced since 1980 may have contributed to the decreasing incidence of human Q fever. PMID- 3324567 TI - Infections with Coxiella burnetii in man and animals in The Netherlands. AB - A serological survey using an indirect micro-immunofluorescence test among people considered to be at risk of contracting an infection with C. burnetii yielded 75.9% seropositives, whereas controls from three geographical regions in the Netherlands showed a mean of 45.5% with considerable differences per region and sex. A comparable retrospective sample from 1968 showed 46% seropositives. Sera from people aged 0 to 19 years yielded 38.3% positives (8). The preliminary data of a survey among cattle using an indirect ELISA showed antibodies against C. burnetii in 21.4% of 1160 animals in 234 dairy herds and lower percentages in other types of herds. Among 3603 sheep from 191 flocks, 3.5% appeared to be seropositive and a limited survey among goats demonstrated specific antibodies in less than 1%. A total of 219 dogs and 26 cats was examined with negative results. The results of a clinical and epidemiological study of 51 cases of human Q fever are summarized. Of these patients, 13 were female and 18 were younger than 3 years of age. In 29 cases the infection could be associated with direct or indirect contact with animals or animal products of different species. Family and other contacts of 29 patients were serologically examined and 61% were positive for specific IgG and 10% also for IgM. In addition, 22 babies from seropositive mothers were serologically examined and none was found positive for specific IgM. The epidemiological implications of these observations are discussed. PMID- 3324568 TI - Q fever in the United Kingdom and Ireland. AB - In Britain, Q fever in man was first reported in 1949. Two years later a serological survey of cattle revealed a prevalence of infection of 2.1%. In the 1970's prevalences of 4.5% and 3.1% were encountered respectively in cows that had aborted or calved normally in central England. In sheep, antibodies to C. burnetii have been detected in approximately 2.8% of sera examined for diagnostic purposes and 0.6% of sheep awaiting export. Since 1975 fewer than 10 incidents of C. burnetii associated disease in cattle have been reported annually while the figure for sheep has been even smaller. Between 100 and 200 cases of human Q fever are encountered annually. The majority are sporadic but occasionally large outbreaks occur. Direct contact with farm livestock or other animals cannot always be established. Despite Public Health interest in Q fever the low economic significance of C. burnetii infection of farm livestock limits opportunities for conjoint medical-veterinary epidemiological investigations. In Ireland, the patterns of animal infection with C. burnetii and of human Q fever are broadly similar to those in Britain. PMID- 3324569 TI - Epidemiology and significance of Q fever in the Federal Republic of Germany. AB - In the Federal Republic of Germany no large Q fever epidemics (more than 200 cases) have been encountered within the last 20 years; however, Q fever was prevalent throughout that period on a constant level (between 27 and 100 officially reported cases per year). Besides classical pneumonic Q fever, chronic forms associated with endocarditis, myocarditis and hepatitis were recently diagnosed for the first time in the Federal Republic of Germany. The disease Q fever in humans is often misdiagnosed as common cold or influenza, and more attention should be paid to this entity by the medical profession. Within ten years there has been a sharp increase of Q fever infections in livestock and pets as proved by seroepidemiologic investigations. Preliminary results of a seroepidemiological study indicate a parallel increase of seropositives in the human population, but further investigations on larger numbers of sera are required for statistic confirmation. There are reasons to believe that, in contrast to general opinion, in the Federal Republic of Germany C. burnetii is involved now in infertility in cattle, and besides being a zoonosis Q fever must be considered as a potentially important infectious disease of cattle causing economic losses in this country. Further investigations on this matter are required. PMID- 3324570 TI - Q fever laboratory diagnostic methods used in Roumania. AB - The methods used presently in Roumania for Q fever laboratory diagnosis are presented. They include Coxiella (C.) burnetii isolation procedures, Q fever serologic tests, and the skin test. The diagnosis by isolation procedures is performed by inoculation into guinea pigs and embryonated eggs. Q fever serologic diagnostic tests are the complement fixation (CF), microagglutination (MA), and IgG-IgM ELISA tests. Results obtained by comparing the CF test with MA and ELISA tests in the diagnosis of acute cases and of previously infected patients are presented. Skin test diagnosis using a C. burnetii corpuscular antigen in animals and a soluble antigen in men was compared with the CF test and proved the reliability of the skin test as an alternative method for Q fever diagnosis, especially in epidemiologic investigations. PMID- 3324571 TI - Detection of Coxiella burnetii by the immunoperoxidase technique. AB - An immunoperoxidase method using Coxiella (C.) burnetii-specific hyperimmune serum raised in rabbits, and swine anti-rabbit horseradish peroxidase conjugate was applied to visualize C. burnetii in BGM cell cultures. The technique proved to be highly specific and did not result in any unspecific background staining. The technique was applied successfully to study the organism during multiplication in vacuoles of epithelial cells and in the phagolysosomes of macrophages. Preliminary results further indicate that the technique may be useful for the detection of the pathogen in tissues and milk samples. PMID- 3324572 TI - Q fever epidemiology in Roumania. AB - A review on Q fever epidemiologic aspects in Roumania from the first case report in 1947 up to the actual cases is presented. It includes the dynamics of the number of cases, features of epidemics, results of surveys on slaughterhouse workers and laboratory-acquired cases, results of serologic surveys in domestic animals, and of wild life studies. Special attention is given to the sporadic character of the present cases in Roumania with emphasis on the seasonal repartition of cases, occupation of subjects, and urban versus rural proportion of cases. The necessity of elucidation of the mechanism of generation of actual cases is emphasized since no relation with the usual animal sources could be established. PMID- 3324573 TI - Q fever vaccines: present status and application in man. AB - Of three Q fever vaccine candidates available at present, i.e., phase I corpuscular untreated, soluble, and phase I corpuscular chloroform-methanol treated vaccines, the first two were tested on hundreds of subjects exposed to Q fever. Based on their sufficient immunogenicity (which depends also on the tests employed) and low reactogenicity (providing that subjects with previous contact with Coxiella (C.) burnetii are excluded from vaccination) these two vaccines can be recommended for vaccination of humans at risk. Further studies are required, however, to answer definitively which vaccine type is the most suitable, and facing the problem of C. burnetii strain heterogeneity, to decide whether a monovalent vaccine will be sufficient or a polyvalent vaccine will be necessary. PMID- 3324575 TI - [Chemonucleolysis. Method, indications and results. Review]. AB - Since 1963 Chemonucleolysis [CNL] with discase and collagenase has served as a supplementation to the surgical approach in the treatment of prolapses of lumbar disks. The world-wide stated rates of successful treatments amount to about 70 per cent. For a further correction of the result surgical treatments are considered to be necessary in about 20 per cent of the cases. Our experience gained with these measures shows a success in 70 per cent of the patients. The frequency of operations still lies around 18 per cent in accordance with the international standard. This therapy, however, should not be considered to be a fully valid alternative or substitute. If exact indications are present, it can make a surgical intervention superfluous in selected cases. PMID- 3324574 TI - Q fever vaccines for animals. AB - The results of different workgroups and those obtained in own investigations with Q fever vaccines for cattle and sheep are reviewed and discussed. In field trials Coxiella (C.) burnetii vaccines of inactivated whole cells (WC) in phase (ph) I as well as WC ph II vaccines prevented infections of cows exposed to naturally infected environments, provided they were vaccinated as noninfected calves. To monitor calves for this purpose the sensitive ELISA has superseded the complement fixation test (CF). WC ph I vaccines failed to prevent shedding by uninfected cattle and sheep which were vaccinated and subsequently challenged by parenteral inoculation with viable organisms, but reduced shedding, and prevented pathological lesions and clinical symptoms. The results obtained in field trials with a commercially available vaccine consisting of killed WC ph II of C. burnetii and inactivated WC of Chlamydia psittaci indicated that vaccination had significantly improved fertility in vaccinated herds. However, the mechanism of protection is unclear because the function of the chlamydial component in this vaccine is not yet defined. Cattle given this vaccine can be distinguished from naturally infected cattle because the former produce predominantly non-complement binding IgG2, detectable by ELISA. This vaccine frequently causes undesirable local reactions. Antigens of C. burnetii (strain "Frankfurt", ph II) prepared by propagation in cell cultures and successive purification by guanidinium hydrochloride- and chloroform/methanol-extraction (CMR), as well as a major protein extracted from these CMR preparations represent potential vaccine candidates without such side effects. PMID- 3324576 TI - Migration of abdominal catheter of ventriculoperitoneal shunt into the scrotum. AB - Two cases are reported in which the abdominal catheters slipped into the scrotum through the unobliterated processus vaginalis. PMID- 3324577 TI - [A new instrument for computerized tomography-guided brain biopsy]. AB - The authors present a new stereotaxic brain biopsy method. After establishment of the CT-and angiographic diagnosis follows the marking of the best suited needle track by means of the CT-scanner Somatom DRG. The trephination is then performed at the operation-theatre during local anesthetization. Repeatedly laying on the CT-table, a low contrasted stereotaxic device is fixed on the patients head. Direction and depth of the puncture are measured and predetermined with an accuracy of +/- 5 mm with a few CT-scans. After guided insertion of a thin-wall nonpaque Teflon-sleeve it is possible to obtain artefactless tomograms or localization control and multiple biopsy probes for histologic evaluation without repeated punctures. Therapeutical interventions may be performed in the same way. PMID- 3324578 TI - A monoclonal antibody to the trichothecene T-2 toxin: screening for the antibody by a direct enzyme immunoassay. PMID- 3324579 TI - [Safety problems in biotechnology. Medical biotechnology and safety]. PMID- 3324580 TI - [Structure of botulinum neurotoxins and their interaction with neuroreceptors]. PMID- 3324581 TI - [Trace elements and infection]. PMID- 3324582 TI - [Comparative study of the morphology and sensitivity to damaging factors of capsular and acapsular variants of Escherichia coli CA 189]. AB - E. coli strain SA 189 has been isolated from a calf with E. coli infection. The cultivation of this strain on a solid culture medium has resulted in its dissociation into two variants due to the loss of the capsule by the cells of the initial culture. Both variants of E. coli strain SA 189 (capsular and acapsular) are equally sensitive to antibiotics. The capsular variant has a narrower range of sensitivity of colicins and shows greater resistance to the bactericidal action of normal blood serum than the acapsular one. Bacteria belonging to these two variants differ perceptibly in the kinetics of disturbances in the barrier properties of their membrane apparatus under the action of cetyltrimethylammonium bromide, a cation detergent. The conditions permitting the differentiation of the capsular and acapsular forms of E. coli strain SA 189 by the kinetics of the damaging action of this detergent have been experimentally selected. PMID- 3324583 TI - [Microcolony morphology as a criterion in bacterial diagnosis. The differentiation of Pneumococcus from alpha-hemolytic Streptococcus]. AB - The authors have developed a method permitting the microscopic study of the morphology of bacteria and their relative position in microcolonies. Thus, the use of this method has made it possible to distinguish Streptococcus pneumoniae from other bacteria by the morphology of their microcolonies. In the study of 75 streptococcal strains, all strains yielding positive results in two or three tests, similarly to all strains pathogenic for mice, formed microcolonies with granular (pneumococcal) morphology, while all strains yielding negative results have been found to form microcolonies with catenulate ("nonpneumococcal") morphology. The authors suggest that the morphology of microcolonies is a more reliable criterion for the identification of S. pneumoniae than other tests used separately. PMID- 3324584 TI - [Effect of the peptide and amino acid composition of nutrient bases on the parameters of microorganism growth]. AB - The parameters of the growth of three microbial strains cultivated in growth media prepared with the use of different nutrient bases, both locally produced and imported, have been studied. The characteristics of the processes of bacterial cultivation have been found to correlate with the peptide composition of hydrolysates used in the experiment. Nutrient bases containing a wide spectrum of peptides with different molecular weight have ensured the most favorable conditions for the growth of microorganisms belonging to the taxonomic groups under study. PMID- 3324585 TI - [Immune system function in candidiasis patients]. AB - To compare the clinical picture and the immunological characteristics, 58 candidiasis patients differing by the severity and dissemination of the disease were examined. Chronic candidiasis of the skin and mucous membranes, the most severe and disseminated form of the disease, is associated with a decrease in the number of T-lymphocytes and changes in their subpopulations, as well as high titers of Candida albicans antigen and antibodies to it in blood sera. The immune system of patients with visceral candidiasis and chronic vulvovaginal candidiasis was similar to that of healthy persons in the characteristics under study. Immediate and mixed hypersensitivity occurred in candidiasis patients more frequently than in healthy persons. In extremely severe forms of Candida infection immediate hypersensitivity prevailed. PMID- 3324586 TI - [Use of liposomes to demonstrate the function of the mononuclear phagocyte system]. AB - The possibility of using liposomes containing an indicator composition (dye or fluorophor) for the determination of the eliminative activity of the system of mononuclear phagocytes (SMP) was studied. Liposomes were obtained by the sonication of the suspension of lecithin, cholesterol and an indicator substance. The rate of the elimination of liposomes from the blood stream after their intravenous injection into Wistar rats (males) was evaluated photometrically or fluorometrically in hemolyzed blood samples taken from the animals at different periods after the injection. The data thus obtained were processed by means of a microcomputer with the use of a specially developed program. The results of this investigation suggest that liposomes can be used for the study of the eliminative activity of SMP. PMID- 3324587 TI - [Comparative analysis of the HBsAg level in human blood preparations]. AB - A total of 218 batches of blood preparations produced from different raw materials have been studied by means of enzyme immunoassay kits (Abbott Laboratories, USA). The assays have revealed that the preparations under study are nonstandard with respect to the content and isolation rate of HBsAg, the marker of hepatitis B virus. These data necessitate search for the ways of improving the quality of blood preparations. PMID- 3324589 TI - [On the 70th anniversary of the Great October Socialist Revolution]. PMID- 3324590 TI - [Diagnosis of Duchenne muscular dystrophy using DNA probes]. PMID- 3324588 TI - [Action of the lactoperoxidase system on Salmonellae and Shigellae]. AB - In vitro experiments have demonstrated that the lactoperoxidase system produces a bactericidal effect on salmonellae and shigellae. The physiological concentrations of the components of this system, making it possible to obtain a pronounced bactericidal effect, have been established. Lactobacilli have been shown to potentiate the effect of the lactoperoxidase system. The possibility of realizing the bactericidal properties of the lactoperoxidase system with respect to salmonellae and shigellae in the preparations of immune lactosera, intended for passive enteral immunization against intestinal infections, has been suggested. PMID- 3324591 TI - The possibilities of real-time sonography in the diagnostics of peripheral pulsating resistances. Our experiences of some cases. AB - Real-time sonography was performed in 5 patients in 7 cases for peripheral pulsating resistances. The change developed in the inguinal fold in one case after arteriography and in 3 patients following a vascular operation. In an additional case, a pulsating mass located in the neck proved to be the kinking of the subclavian artery. After a brief literary review of the ultrasound diagnostics of the vessels, the authors have found sonography a suitable means for judging the relationship between the vessel or graft and the pseudoaneurysm, the size of the communication and eventual thrombus formation. PMID- 3324592 TI - Examination of lymph and bile composition following experimental liver transplantation in rat. AB - The lymph flow of the thoracic duct, the protein content of the lymph, bile flow and bile composition are studied during the first three hours of the recirculation phase in experimental liver transplantation. It is established that the lymph flow and the protein content of the thoracic duct decrease as a result of the interruption of hepatic lymph flow of a high protein concentration. The change in bile composition and flow is due to the reduced bile acid excretion of the transplanted hepatic tissue. PMID- 3324593 TI - Peritoneal lavage in the diagnosis of the acute abdomen of non-traumatic origin. Clinical review. PMID- 3324595 TI - Location of parathyroid glands by thallium-technetium subtraction scintigraphy. AB - In 36 patients with biochemical and clinical evidence of primary or secondary hyperparathyroidism (HPT), preoperative scintigraphic studies were performed with a thallium-technetium subtraction technique. The patients were given 30 MBq technetium pertechnetate and, after a delay of 10-15 minutes, 55 MBq thallium chloride. Data were collected with a gamma camera equipped with a pinhole collimator and dedicated computer. Images were recorded simultaneously in two channels, in order to provide identical positioning for the thallium and technetium images. A standardized gradual computer subtraction was then carried out. Parathyroid adenoma was present in 28 patients, primary parathyroid hyperplasia in two, and secondary hyperplasia due to chronic renal failure in six. The scintigrams located 24 (86%) of the adenomas, but only four (13%) of the total 32 hyperplastic glands. The scintigraphic technique offers considerable advantages in the preoperative location of parathyroid adenomas, which may be of particular interest in persistent or recurrent HPT. PMID- 3324594 TI - Single-dose v. short-term antibiotic therapy for prevention of wound infection in general surgery. A prospective, randomized double-blind trial. AB - To investigate the effectiveness of a single-dose antibiotic regimen for preventing postoperative wound infection, a prospective, randomized double-blind trial was carried out in patients undergoing "clean-contaminated", "contaminated" or "clean" (vascular) surgery. Both elective and emergency operations were included. Single-dose (preoperative) prophylaxis was compared with short-term prophylaxis (1 dose preoperatively and 2 doses postoperatively). The antibiotics were penicillin, tobramycin and metronidazole in various combinations, and comparisons between single-dose and short-term prophylaxis were made with all the regimens. The incidence of wound infection was 5/277 (1.8%) in the short-term group and 9/287 (3.1%) in the single-dose group. The difference was not statistically significant. Nor was statistically significant difference found when the type of operation and the degree of contamination were considered. Single-dose antibiotic prophylaxis thus gave a low incidence of postoperative wound infection, even in "clean-contaminated" or "contaminated" cases. PMID- 3324597 TI - Acute appendicitis caused by metallic foreign body (bullet). Case report. AB - In a patient who had sustained bullet wounding 9 years previously, acute appendicitis was associated with presence of a bullet in the appendix. The case is described. PMID- 3324596 TI - Linear incision and curettage vs. deroofing and drainage in subcutaneous abscess. A randomized clinical trial. AB - Linear incision plus curettage under antibiotic cover was compared with conventional deroofing and drainage of subcutaneous abscess in a randomized study of 50 patients. The median healing time was 9 days following linear incision and curettage and 15 days after deroofing and drainage (p less than 0.05). There was no recurrence of abscess during follow-up for 6 months. Linear incision plus curettage under single-dose antibiotic cover thus proved to be a safe method with significantly shorter healing time than after conventional deroofing an drainage. PMID- 3324598 TI - Interrelation of B lymphoid malignancies. PMID- 3324599 TI - Randomized comparison of imipenem/cilastatin and ceftazidime in the empiric therapy of severe abdominal infections. A multicenter study. PMID- 3324600 TI - Drugs recently released in Belgium. Carboplatin, cefmenoxime, zidovudine. PMID- 3324601 TI - Photosensitive psoriasis. Epidemiological, clinical and experimental studies. PMID- 3324602 TI - A bibliography of epidermolysis bullosa. PMID- 3324603 TI - In memoriam Ronald S. Wilson 1933-1986. PMID- 3324604 TI - Birthweight differences, the transfusion syndrome and the cognitive development of monozygotic twins. AB - Monochorionic twins may differ from dichorionic monozygotic (MZ) twins because of the transfusion syndrome and the timing of the cleavage of the zygote. Intrapair birthweight differences may be an indicator of these intrauterine variables. Previous evidence concerning weight differences and intellectual ability in MZ twins is reviewed with recommendations that future research also incorporates full placental data. Poorer scores on a nonverbal test are found for the lighter male twin of pairs with large intrapair differences in birthweight. Co-twin concordance rates for test scores are also highest for this group indicating that they vary consistently from other groups. Some evidence is presented from the present and earlier studies implicating anomalies of asymmetry or the transfusion syndrome as possible causes of these differences in brain functioning. The study adds further doubts as to the validity of any assumption of developmental equivalence between MZ twins and the general population. PMID- 3324605 TI - [A case of high molecular weight kininogen deficiency--problem of its laboratory diagnosis and low molecular weight kininogen]. PMID- 3324606 TI - [Genetics in clinical hematology. I. The principles of clinical genetics]. PMID- 3324607 TI - [Genetics in clinical hematology. II. Genetically determined hematologic diseases]. PMID- 3324608 TI - [Mast cells and basophil granulocytes]. PMID- 3324609 TI - [Megakaryoblastic leukemia--theories and controversies]. PMID- 3324610 TI - Hemodynamic monitoring: from catheter to display. PMID- 3324611 TI - Respiratory alkalosis: physiological implications and clinical consequences. PMID- 3324612 TI - Buprenorphine as premedication and as analgesic during and after light isoflurane N2O-O2 anaesthesia. A comparison with oxycodone plus fentanyl. AB - Sixty patients undergoing gynaecological laparotomies under isoflurane anaesthesia received 0.4 mg of buprenorphine sublingually or 0.12 mg/kg of oxycodone intramuscularly in random order for preanaesthetic medication. Patients premedicated with buprenorphine were given buprenorphine before, during and after anaesthesia and patients premedicated with oxycodone received fentanyl before and during anaesthesia and oxycodone after anaesthesia. Buprenorphine premedication produced less drowsiness and sedation and alleviated patients' apprehension significantly (P less than 0.05) less than oxycodone. Systolic and diastolic blood pressure and heart rate were significantly (P less than 0.05 to P less than 0.01) higher after intubation in the buprenorphine group when compared with the oxycodone plus fentanyl group. After anaesthesia, spontaneous respiration started rapidly; the return of consciousness and immediate recovery occurred at the same rate in both groups. In the recovery room moderate to severe pain was more common (P less than 0.05) in the oxycodone plus fentanyl group than in the buprenorphine group. The respiratory rate in the recovery room was lower among patients given buprenorphine, and two patients given buprenorphine developed severe respiratory depression. In the ward (2 to 24 h after operation) sublingual buprenorphine provided pain relief as good as intramuscularly administered oxycodone. No differences were noted in the incidence or severity of emetic symptoms between the groups. It is concluded that buprenorphine can provide good postoperative pain relief for gynaecological laparotomies performed under light isoflurane anaesthesia, but patients need to be monitored carefully after operation because of the possibility of respiratory depression. PMID- 3324614 TI - Effects of PEEP on extravascular lung water and central blood volume in the dog. AB - Twenty-four mongrel dogs were anaesthetized and ventilated mechanically in the supine position. Extravascular lung water (EVLW) and central blood volume (CBV) were measured with a double indicator (dye/cold) dilution technique. Both indicators were detected intravascularly in the aortic root with a fibreoptic thermistor catheter. Seven dogs ventilated with a positive end-expiratory pressure (PEEP) of 1.0 kPa (10 cmH2O) for a short period of time (less than 20 min) displayed no significant change in EVLW as measured with the indicator dilution technique (= EVLWi), while reductions were seen in both CBV (15%, P less than 0.01) and cardiac output (CO-thermodilution technique) (10%, P less than 0.05). Another seven dogs ventilated with a PEEP of 1.0 kPa for 8 h showed a gradual increase in EVLWi. After 8 h, a mean increase of 34% (P less than 0.01) was recorded, and the increase was also verified by post-mortem gravimetric determination of EVLW (= EVLWg), displaying an increase of 61% (P less than 0.01). In five dogs ventilated with zero end-expiratory pressure (ZEEP) for 8 h, no changes in EVLWi, CO, and CBV were observed, and EVLWg was mean 4.39 g/kg body weight (BW). Five additional dogs were sacrificed after 15 min of anaesthesia without catheterization and EVLWg was found to be 4.24 g/kg BW. It is concluded that EVLWi does not change measurably during ZEEP or short periods of PEEP. However, long periods (8 h) of PEEP result in elevated EVLWi values. Gravimetry supports these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324613 TI - Decrease in serum potassium concentration during epidural anaesthesia. AB - A mean decrease in the arterial serum potassium concentration (S-K) of 0.40 mmol/l (range 0-1.0) was found in 45 elderly men who were studied before and after induction of epidural anaesthesia (using mepivacaine 2% with adrenaline). The decrease was similar in patients who received acetated Ringer solution or dextran 40 in normal saline as intravenous fluid supplementation. No difference in S-K change was found between patients with a normal (less than 115 mumol/l) or elevated serum creatinine concentration. The decrease in S-K prevailed at the end of surgery except in patients with an elevated serum creatinine. Corrections of S K for changes in arterial blood pH and rectal temperature during induction of anaesthesia did not explain the decrease in S-K. Correlations of clinical parameters such as the extension of anaesthesia, amount of intravenous fluid given and blood pressure changes gave conflicting results. A smaller decrease or no change in S-K was usually seen in arterial (n = 7) and venous (n = 7) samples when no intravenous fluid was given, as well as in venous samples when acetated Ringer solution was given (n = 6). PMID- 3324615 TI - Intravenous diclofenac sodium decreases prostaglandin synthesis and postoperative symptoms after general anaesthesia in outpatients undergoing dental surgery. AB - One hundred unpremedicated patients scheduled for outpatient restorative dentistry and/or oral surgery were given either 75 mg diclofenac sodium (prostaglandin synthesis inhibitor) or a saline placebo i.v. in a double-blind random fashion before induction of anaesthesia with methohexitone (2 mg/kg). Intubation was facilitated with suxamethonium (1.2 mg/kg) and anaesthesia was maintained with isoflurane in 50% nitrous oxide and oxygen using spontaneous respiration. Cuff pressure was continuously monitored and maintained at 10-25 mmHg. The mean duration of anaesthesia was 141 +/- 75 min in the diclofenac group and 150 +/- 73 min in the saline group. Diclofenac inhibited prostaglandin synthesis, as evident from serum thromboxane B2 and urinary 6-keto-prostaglandin F1 alpha data. There was no difference in recovery as assessed from the orientation time (14.2 +/- 5.7 min and 14.5 +/- 6.3 min for diclofenac and saline patients, respectively), perceptual speed and ability to walk along a straight line 30 and 60 min after anaesthesia. Emetic symptoms were equally common in both groups: an overall incidence of 32.6% and 36.7% for the diclofenac and saline patients, respectively. In the whole patient series women became nauseated and vomited more than men (P less than 0.01). Diclofenac reduced the incidence of pain in the throat or oral region 1 h after anaesthesia (P less than 0.05) and other symptoms 1-24 h postoperatively (P less than 0.01). Thus, preoperative intravenous diclofenac appears useful in ambulatory patients undergoing restorative dentistry and oral surgery under isoflurane anaesthesia. PMID- 3324616 TI - Patient-controlled analgesia: a controlled trial. AB - Thirty-six patients undergoing lower abdominal surgery were included in a prospective randomized controlled study to compare the effects of patient controlled analgesia (PCA) and a standard intramuscular/intravenous treatment (conventional analgesia, CA) of postoperative pain. Morphine was used in both groups. There were no significant differences between the two analgesic regimens in respect of linear analogue pain scores, verbal pain-relief scores, amount of morphine used or side-effects. No treatment-induced alterations in vital values were experienced. PMID- 3324617 TI - Insensible water loss and its assessment in adult patients: a review. AB - The nature, magnitude and factors influencing insensible water loss are discussed. A brief overview of the current practice of estimating insensible perspiration in Sweden is presented. Finally, a suggestion is put forward regarding a simplified formula for estimating insensible water loss in adult patients, based on information currently available in the literature. PMID- 3324618 TI - Low-dose acetylsalicylic acid (ASA) plus dipyridamole versus dipyridamole alone in the prevention of stroke in patients with reversible ischemic attacks. AB - A total of 243 patients who had reversible ischemic attacks (RIA) were submitted to clinical trial to determine whether dipyridamole (400 mg/day) (D) or aspirin (100 mg/48 hours) + dipyridamole (300 mg/day) (ASA + D) would produce significant reduction in the subsequent occurrence of RIA and completed stroke. One hundred and fifteen were selected for Group ASA + D and 71 were treated with dipyridamole only. The treatment groups were similar in relation to age, sex, risk factors, duration and presumed vascular territory of RIA, incidence of alterations of arterial supra-aortic trunks, cerebral infarct (CT scan), and platelet function. Patients were followed for a mean time of 21 months. At the end of the study, 21.7% of the ASA + D group and 19.7% in the D group had suffered new episodes of RIA or completed stroke (p = 0.88). Frequency of stroke (reversible ischemic neurologic deficit or completed stroke) was 7.8% in the ASA + D patients and 9.8% in the D patients (p = 0.83). Subgroup analysis did not show significant differences either. It is concluded that ASA + D has no significantly greater beneficial effect than that observed with D alone in the secondary prevention of atherothrombotic cerebral ischemia. However, a statistical Type II error cannot be excluded by the reduced number of recurrences. PMID- 3324619 TI - Creutzfeldt-Jakob disease with plaques and paired helical filaments. AB - A 32-year-old man with rapidly progressive dementia, pyramidal signs, myoclonic jerks and dystonic movements died following brain biopsy. neuropathological examination revealed minimal neuronal loss accompanied by mild spongiform change and astrocytic reaction. Numerous plaques and neurofibrillary tangles composed of paired helical filaments dominated the ultrastructural picture. This patient had features of both Creutzfeldt-Jakob disease and Alzheimer's disease, providing additional support for the existence of an overlap between these disorders. PMID- 3324620 TI - Cerebral blood flow in migraine and cortical spreading depression. AB - Migraine is a common disease which expresses itself by paroxysmal headache, commonly accompanied by transient neurological symptoms. There are at the moment two important theories concerning the cerebral mechanisms of migraine: The vascular theory which attributes migraine to spasm of a cerebral artery causing local hypoxia and transient focal symptoms followed by neurogenically mediated extra- and/or intracranial vasodilation causing headache, i.e. migraine is understood in terms of a primary perturbation of blood vessel function. Another, but neglected viewpoint relates migraine to a paroxysmal, transient depolarization of primarily cortical neurones causing transient focal symptoms and headache, i.e. migraine is understood in terms of a primary perturbance of neuronal function. This review summarizes clinical and experimental studies concerning these two theories with special emphasis on classic migraine, i.e. paroxysmal headache accompanied by focal symptoms of short duration. At begin of the classic migraine attack regional cerebral blood flow (rCBF) declines in the posterior part of the brain. Subsequently the hypoperfused region expands anteriorly, independent of the territories of supply of the large cerebral arteries. This observation speaks clearly against reduced perfusion as consequence of arterial spasm. The rate of spread of the reduced perfusion is about 2 mm/min and the changes of perfusion appear to follow the cortex corresponding to the convexities. Tests of regulation of rCBF show normal blood pressure autoregulation, but reduced responsiveness to change of arterial carbon dioxide tension and in response to mental activation. These observations are consistent with arteriolar vasoconstriction as cause of reduced perfusion. Vascular tone at the arteriolar level is, however, mainly determined by local factors, and change of local neuronal function could therefore be the basis of increased arteriolar tone and reduced rCBF. Analysis of the time course of perfusion reduction and symptoms reveals that perfusion frequently declines before the patient experiences any focal symptoms. The focal symptoms frequently start after spread of the hypoperfusion has begun, but usually ceases altogether within another 30 minutes, while the reduced perfusion persists for a couple of hours, when the patient suffers from headache. This temporal relationship between symptoms and rCBF changes precludes that the focal symptoms are secondary to reduced rCBF. Furthermore, migraine headache is not related to increased rCBF. On this background the acute migraine attack can hardly be explained by a primary arterial vasospasm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3324621 TI - Morphological detection of neurogenic muscle disorders: how can statistical methods aid diagnosis? AB - The light microscopical observation of groups of histochemically similar muscle fibres, referred to as fibre-type grouping, is commonly considered to be evidence of a denervation and reinnervation process affecting the spinal motor neurons or the peripheral nerves. It can be difficult to assess whether such groups have occurred by chance or are due to a slowly progressive pathological process in an early stage of development. Consequently, there is a need for one or more objective methods for assessing the fibre-type arrangement in healthy and diseased human muscles. The purposes here are to review the methods for the detection of fibre-type grouping that have been published in the last two decades, to describe some unsolved problems, and to indicate some likely lines of development. PMID- 3324624 TI - The effect of different prosthetic restorations on the dietary selection in edentulous patients. A longitudinal study of patients initially treated with optimal complete dentures and finally with tissue-integrated prostheses. AB - The effect of prosthetic restoration of masticatory ability on dietary selection was evaluated in 23 edentulous patients with denture adaptation problems. The patients were first given optimal complete dentures and then a fixed prosthesis on tissue-integrated implants in the lower jaw. Changes in dietary selection were evaluated from 4-day records obtained before prosthetic treatment and on six occasions up to 78 months after treatment. With the method used, no significant changes in food selection were recorded during the rehabilitation period, except for a slight increase in intake of crisp bread and fresh fruit after treatment with fixed tissue-integrated prostheses in the mandibular jaw. It is concluded that an improved oral function will not in itself lead to a change in dietary selection and that dietary changes probably require professional and individually given dietary advice by a trained dietitian. PMID- 3324622 TI - Measles virus matrix protein gene expression in a subacute sclerosing panencephalitis patient brain and virus isolate demonstrated by cDNA hybridization and immunocytochemistry. AB - Subacute sclerosing panencephalitis (SSPE) is a rare, fatal disease of children caused by a persistent measles virus infection of the central nervous system. A defect in synthesis of measles virus matrix (M) protein may be a factor in virus persistence in the brain. This study details attempts to detect expression of M protein in the brain of an SSPE patient, in the cell-associated virus isolated from this brain, and in brains of ferrets inoculated with the isolate. In situ hybridization with a tritiated cloned cDNA probe was used to search for RNA encoding M protein. Immunostaining with monospecific antiserum and the avidin biotin-peroxidase technique was done to locate the polypeptide. The data obtained indicate that although nucleotide sequences coding for M protein were detected in the patient and ferret brains, expression of M protein in these tissues could not be detected. In the culture SSPE virus isolate, the results were the same until the infected cells were examined by electron microscopy and a very limited expression of M protein was revealed. This suggests either diminished synthesis and/or rapid degradation of M protein in this cell-associated virus strain. PMID- 3324625 TI - Irreversible immune reactions following keratoplasty. Retrospective clinical and histological evaluation of graft failure in a material of 206 consecutive eyes. AB - A total of 16/206 eyes in 14/186 patients developed irreversible immune reactions. 15 of the rejected eyes belonged to the 'classical' risk groups, i.e. systemic immune disorders (3/3), metaherpetic keratitis (6/41), pseudophakic bullous keratopathy with inflammation (2/6), non herpetic keratitis with vessel invasion (1/23) and 3 regrafts not included in these groups (a total of 7/31 regrafted eyes rejected). Only 1 rejection occurred in the low-risk groups: an aphakic eye with bullous keratopathy. Histopathological examination revealed that discs which later developed irreversible immune reactions had invariably been grafted in eyes which had vascular invasion and/or inflammation of the recipient cornea. In all, 55/206 eyes ended up with opaque grafts, i.e. irreversible immune reactions were responsible for about one third to one-quarter of the graft failures in the present material. The irreversible immune reactions in the material must be considered 'minimum values', since possible abortive, torpid immune reactions may have escaped recording. PMID- 3324623 TI - Substantia nigra damage induced by ischemia in hyperglycemic rats. A light and electron microscopic study. AB - Preischemic hyperglycemia induced by feeding or glucose infusion worsens the brain damage and the clinical outcome following ischemia of a given duration and density, and characteristically causes postischemic seizure activity. Light microscopy has previously showed that, in the rat, transient hyperglycemia ischemia induced by bilateral carotid occlusion in combination with arterial hypotension causes a uni- or bilateral lesion in the pars reticulata of the substantia nigra. Since this region has a central role in preventing seizure discharges the present study was carried out to determine the ultrastructural characteristics of this lesion. In rats with 10 min of transient hyperglycemic ischemia followed by recirculation for 1 to 18 h, the pars reticulata of the substantia nigra showed signs of status spongiosus, as well as extensive nerve cell alterations. These changes were observed after all recovery periods studied. The spongiotic appearance was mainly caused by swelling of dendrites and, to a lesser degree, by astrocytic swelling. The dendrites were expanded at all recovery times but the severity increased during the later periods of recirculation. These swollen dendrites contained severely expanded mitochondrias and endoplasmic reticulum. The cytoskeletal elements showed disordered lining of microtubules. Two major types of nerve cell alterations were present: a "pale" and a "dark" variety. The pale type was the most frequent cell alteration. It occurred in all experimental groups and at all time points. Redistribution of the nuclear chromatin and of cytoplasmic organelles as well as swelling of the same type as in the dendrites were the essential changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324626 TI - Danish ophthalmology at the University of Copenhagen. 100th anniversary of the Chair 26. April 1888-26 April 1988. PMID- 3324627 TI - [Osteogenesis imperfecta. Various observations based on 7 cases]. PMID- 3324628 TI - Acute rupture of the tendo calcaneus. Surgical repair with functional aftertreatment. PMID- 3324629 TI - A protease inhibitor from human allergic nasal secretions. AB - Protease and antiprotease activities were estimated in nasal secretions from patients with chronic sinusitis and nasal allergy, using [3H]-casein as substrate. In the purulent nasal secretions, strong protease activity was measured, but there was less activity in the allergic nasal secretions. In contrast, trypsin inhibitory activity in allergic nasal secretions was much higher than in nasal secretions from the patients with chronic sinusitis. A protease inhibitor was partially isolated from nasal secretions of the nasal allergic patients by Sephadex G-150 gel chromatography and characterized. This protease inhibitor has an apparent molecular weight of 10,000 D, determined by SDS-polyacrylamidegel electrophoresis. It depresses the activities of bovine pancreatic trypsin, bovine pancreatic chymotrypsin and proteases in nasal purulent secretions, whereas it does not inhibit porcine pancreatic elastase, papain, or human plasmin. PMID- 3324631 TI - Treatment of tympanic membrane perforations with hyaluronan in an open pilot study of unselected patients. AB - Twenty-five unselected tympanic membrane (TM) perforations of varying size and duration, from one day to 10 years, were treated by local application of the glycosaminoglycan, hyaluronan, 1%. The treatment was well tolerated without any side-effects. Seventeen of the perforations were closed, though two drums were re perforated. Four perforations not completely covered were markedly reduced in size. No effect of hyaluronan could be observed on moist perforations. The scar formed after treatment with hyaluronan 'normal' appearance. Hyaluronan treatment seems to be an alternative to myringoplasty when treating small and medium-sized dry perforations. PMID- 3324630 TI - Differences in innervation and secretory behaviour of two nasal glandular parts in the rat. AB - The submucosal glands in the rat nose are characterized by the presence of both neutral and acid glycoproteins, which are important constituents of nasal and tracheobronchial secretions. This study is an attempt to gain a better insight into the secretion of these two types of glycoproteins and its neural regulation. Radiobiochemical experiments show a higher sensitivity to methacholine of the nasal glandular region producing acid glycoproteins than the area secreting neutral glycoproteins. Radioligand receptor binding suggests that the binding parameters of the muscarinic receptors in these two areas are mutually different. Furthermore, rat nasal glandular muscarinic receptors appear to be different from those in smooth muscle of rat ileum. PMID- 3324632 TI - The formation of the nasal septum and the etiology of septal deformity. The concept of evolutionary paradox. PMID- 3324633 TI - Spanish multicentre trial on somatrem (1985-1986). AB - In an open multicentre trial, the safety and efficacy of somatrem, 4 IU i.m. three times weekly for 12 months, were evaluated in children with hGH deficiency with or without previous treatment with pituitary hGH. Patients were divided into young and prepubertal groups according to chronological age, and catch-up growth after treatment was greater in the former. Bone age evolved at the same rate as chronological age, irrespective of whether patients were previously untreated (naive) or previously treated. Fewer previously treated patients exhibited anti hGH antibodies than naive patients. Somatrem appears to be a safe, efficient product for treating different degrees of hGH deficiency. PMID- 3324634 TI - Multicentre clinical trial of authentic recombinant somatropin in growth hormone deficiency. AB - A German multicentre trial of recombinant somatropin was commenced in March 1986. A total of 77 patients with hGH deficiency were recruited, with heights at least 2.5 SD below the normal mean. Of these, 49 were previously untreated (naive) and 28 had previously received pituitary hGH. Recombinant somatropin, 12 IU/m2/week was administered subcutaneously, divided into six doses. In the naive group, the height velocity reached 14.9 cm/year in the first 3 months, and thereafter stabilized at 12 cm/year. In the previously treated patients, the growth rate was 10.7 cm/year in the first 3 months, and 8.5 cm/year at 9 and 12 months. There were no abnormal findings in tests of laboratory parameters. No anti-hGH antibodies were detected in any of the patients; seven patients had anti-ECP antibodies, but in six of these the antibodies were already present before treatment. PMID- 3324635 TI - Current clinical trials with authentic recombinant somatropin in Japan. AB - A total of 25 children with hGH deficiency were treated with recombinant somatropin, 0.5 IU/kg/week i.m. for approximately 12 months in a multicentre study. Sixteen patients were previously untreated with any hGH preparation (naive group) and 9 patients had been treated with pituitary hGH for 4-42 months (previously treated group). The height gain after 12 months with the present treatment was 7.7 +/- 1.8 cm/year in the naive group and 5.8 +/- 1.0 cm/year in the previously treated group. Using the criteria proposed by the Foundation for Growth Science in Japan, recombinant somatropin treatment was effective in 15 of 16 patients (93.8%) of the naive group and in all of the 9 patients (100%) in the switched group. Anti-hGH antibody was observed in none of 9 patients in the previously treated group throughout the study period. It was observed in only 2 of 16 patients after 6 months of treatment and 1 of 16 patients after 12 months of treatment in the naive group. No side-effects or abnormalities in laboratory findings were observed. PMID- 3324636 TI - Clinical experience with Genotropin worldwide: an update March 1987. AB - The efficacy and safety of Genotropin (recombinant somatropin, KabiVitrum AB, Sweden) was analysed in 199 children with hGH deficiency, comprising a combined series of four current multicentre trials. Stimulation of linear growth from pretreatment height velocities of 3-4 cm/year to about 10 cm/year was observed after 6 and 9 months of treatment. Statistical analysis revealed significantly greater height velocities (by 2-3 cm/year) when the weekly dose of the hormone was given in 6-7 injections rather than in 3 injections. Immunogenicity seems to be very low, with only about 2% of the children having detectable antibodies during treatment. PMID- 3324637 TI - Physiological role of growth hormone in adult life. AB - Some historical background on the physiological effects of pituitary gland extract and later of purified hGH in experimental animals is given, and the regulatory role of hGH in the human adult is reviewed. The effects of hGH on carbohydrate, protein and lipid metabolism are complex and closely linked to the action of other hormones, particularly insulin. PMID- 3324638 TI - Early initiation of growth hormone treatment: influence on final height. AB - Retrospective growth data for 34 hGH deficient patients who had been treated for at least 3 years with hGH were analysed in a Belgian multicentre study. Final height was related to target height and was usually below it, but it was not determined by chronological or bone ages, bone age delay, height velocity before or during therapy, nor by duration of treatment. Total height gain during long term substitution with hGH is inversely related to chronological and bone ages at the start of therapy, and is positively related to the duration of therapy. Early diagnosis of hGH deficiency is thus important, as it allows catch-up growth to optimal height before puberty, which in turn results in a good pubertal growth spurt. PMID- 3324639 TI - Urine growth hormone determinations compared with other methods in the assessment of growth hormone secretion. AB - Urinary excretion of hGH was studied in children with short stature using a sensitive sandwich enzyme immunoassay technique. Urinary hGH excretion, in terms of hGH: creatinine ratio, showed excellent correlation with the mean and peak hGH values during physiological and pharmacological tests. It seems that the urinary hGH levels reflect serum hGH profiles during the urine collection period. A border zone for the lower limits of normal hGH levels in the urine was 7.5-13.4 ng/g creatinine for the physiological test at night (from 2000 hours to 0600 hours) and 17.4-35.0 ng/g creatinine for the pharmacological tests. Assessment of hGH secretory status by the urinary hGH levels showed good agreement with the serum hGH response. Measurement of urinary hGH could be used as a diagnostic test for impaired hGH secretion, and the multiple blood drawing required in physiological and pharmacological tests might be replaced by urine sampling. PMID- 3324640 TI - An attempt to assess the replacement dose of human growth hormone in the treatment of growth hormone deficient children. AB - In 25 patients with hGH deficiency, who had been treated long-term with hGH, the mode of hGH administration was switched from the conventional method (0.3-0.5 IU/kg/week, in two or three divided doses, intramuscularly) to daily subcutaneous injection at 1900-2100 hours with a dose of 0.46 +/- 0.07 IU/kg/week (equivalent to 14.7 +/- 2.0 IU/m2/week). After 1-3 months of this new mode of hGH administration, blood and urine were sampled at 0900 hours after overnight fasting. Blood glucose, plasma insulin, plasma IGF-1 and plasma total IGF (after extraction) were analysed in blood samples. IGF-1 and hGH were measured in urine samples. These measurements indicated that the dose studied was close to a replacement one, but might be slightly higher than the exact replacement dose. PMID- 3324641 TI - Idiopathic portal hypertension associated with polyclonal hyperimmunoglobulinemia. A case report and review of the literature. AB - We report a case of idiopathic portal hypertension associated with prominent polyclonal hyperimmunoglobulinemia and plasmacytosis in the bone marrow and the spleen. Microscopic examination of the liver showed chronic inflammation in the portal area and abnormal vasculature adjacent to the portal tracts. In the spleen, polyclonal plasma cell proliferation was demonstrated histochemically in addition to the presence of remarkable sinus hyperplasia and periarterial fibrosis. In the present case, a chronic inflammatory state such as connective tissue disease was strongly suspected to exist in the liver, since pancytopenia and hyperimmunoglobulinemia persisted even after splenectomy. It is suggested that the pathogenesis in the present case may have been due to this chronic inflammatory state. PMID- 3324642 TI - Appendiceal endometriosis in pregnancy. Report of a case with perforation and review of the literature. AB - A 25-year old woman at the 26th week of gestation underwent surgery for possible acute appendicitis. Pathological examination of the appendix showed extensive decidual change through the entire wall with perforation and surrounding acute inflammatory cell infiltration. To our knowledge, the present report is the second case of appendiceal endometriosis with this rare complication in the literature. The previously reported cases of appendiceal endometriosis which manifested clinically during pregnancy are briefly reviewed. PMID- 3324643 TI - Leiomyoblastoma of the greater omentum. A case report and review of literature. AB - A case of leiomyoblastoma of the greater omentum, occurring in a 36-year-old man was described. Leiomyoblastoma of the omentum is extremely rare and only 6 cases have been reported in the Japanese and English literature up to date. According to the review of these cases, including the present case, 1) females were affected more frequently than males, and the age ranged from 36 to 76 years; 2) leiomyoblastoma was usually a large tumor which caused abdominal fullness and pain, and occasionally complicated with anemia and bloody ascites; 3) mitosis was rare, and there was no sign of metastasis and recurrence. Finally the morphological criteria and clinical parameters of malignancy in leiomyoblastoma were discussed. PMID- 3324644 TI - Recent advances concerning the cough reflex (chairman's introduction). PMID- 3324645 TI - A new conventional and high-frequency ventilator for small animals. AB - A pressure limited, time controlled ventilator has been designed especially for studies on experimental animals with severe respiratory distress syndrome (SRDS). Inspiration: Expiration (I:E) ratio (1:99-99:1) and frequency can be changed independently. Frequency ranged from 1 to 199/min in conventional ventilation (CV), while in high-frequency jet ventilation (HFJV) from 1 to 30 Hz. The gas delivery system consists of 3 magnetic valves (inspiration, expiration and HFJV, respectively) to ensure superposition of CV with HFJ or to use them separately. A monitoring unit switches off inspiration gas sources during HFJV if intratracheal pressure exceeds the alarm threshold. The device has been used in the following animal models: premature newborn rabbits with surfactant deficient lungs, emphysematous rats and guinea pigs as well as dogs and rabbits with SRDS due to lung lavage. Ventilation was most effective with an I:E ratio of 4:1 during pressure controlled CV, whereas during HFJV optimum gas exchange could be maintained with an I:E ratio of 1:4 and a frequency of 15 Hz in beagle dogs and 10 Hz in rabbits, respectively. PMID- 3324646 TI - [Evaluation of the stability of short-acting insulin preparations]. PMID- 3324647 TI - The prevalence of dementia: a quantitative integration of the literature. AB - Data from studies of dementia prevalence between 1945 to 1985 were analyzed statistically. Prevalence rates were found to vary as a function of methodological differences between studies. However, despite these differences, the relationship between prevalence and age was found to be consistent across studies, with rates doubling every 5.1 years. Across studies, Alzheimer's disease (AD) was found to be more common in women, with a tendency for multi-infarct dementia (MID) to be more common in men. There were also national differences in the relative prevalence of AD and MID, with MID being more common in Japanese and Russian studies, no difference in Finnish and American studies, and an excess of AD in other Western European countries. PMID- 3324648 TI - Citalopram versus maprotiline: a controlled, clinical multicentre trial in depressed patients. AB - In a double-blind trial, comprising 96 depressed patients, citalopram was compared with maprotiline. The trial period was 6 weeks with ratings (MADRS, CGI) and side effects recordings taking place at Weeks 0, 1, 2, 4, and 6. Both drugs were administered as a single evening dose, 40 or 60 mg for citalopram, and 75 or 150 mg for maprotiline. MADRS total scores and CGI scores showed a highly significant reduction in both groups with no significant difference between them, whether the groups were considered as a whole or whether they were subdivided into endogenously/non-endogenously depressed or melancholic/non-melancholic patients. Side effects were not significantly different, but the maprotiline group showed more anticholinergic side effects, whereas the citalopram group showed more nausea, increased sweating and headache. Two patients on maprotiline were withdrawn because of side effects (hypotension and somnolence in the one case; tremor and insomnia in the other). One patient in each group was withdrawn because of increased transaminases, the citalopram-treated patient having increased values, however, already at baseline. Apart from this, no cardiovascular side effects and no pathological laboratory values related to treatment were observed. The authors conclude that citalopram is a safe antidepressant drug and as effective as maprotiline. PMID- 3324649 TI - Intrasphenoidal encephaloceles--a clinical entity. AB - In the current classification basal encephaloceles are grouped together with real transsphenoidal encephaloceles. But those encephaloceles extending only into but not through the sphenoid sinus seem to represent a specific clinical entity and therefore should be regarded as a rare subgroup of sphenoidal encephaloceles. One personal case and six cases from the literature are reviewed, the own case being associated with an empty sella turcica. The initial sign is rhinorrhea, almost invariably. The association with other intracranial anomalies is uncommon. The extradural transsphenoidal or transethmoidal midline approach accompanied by a shunting procedure today is the most suitable method of surgical treatment. PMID- 3324651 TI - Electrically elicited blink reflex and early acoustic evoked potentials in circumscribed and diffuse brain stem lesions. AB - In the present paper, the function of the brain stem in patients with brain stem lesions of various aetiology is investigated with electrophysiological methods. The clinical observations are supplemented by experimental investigations on cats, in which the blink reflex and the early acoustic evoked potentials were registered during the acute elevation of intracranial pressure. The findings in patients with circumscribed space-occupying lesions in the posterior fossa document that the registration of the BR and the BAEP have a functional diagnostic significance above and beyond the neurological and radiological investigation. In the case of the cerebellar space occupations, specific alterations could not be observed. On the contrary, the alterations of BR and BAEP indicate a general disturbance of brain stem function, possibly as a result of a general increase of intracranial pressure. In cerebellopontine angle tumours, both BR and BAEP showed specific alterations which were usually asymmetrical. The BR changes ipsilateral to the tumour are of major topodiagnostic significance, whereas the alterations of the contralateral potential are especially informative in the registration of BAEP. The alterations of BR and BAEP also allow an appraisal of the localization and extent of the lesion in primary space occupations in the brain stem: A pathological R1 indicates a pontine lesion, whereas pathological R2 responses are found in medullary and in oral pontine and mesencephalic lesions. In contrast to cerebellopontine angle tumours, the BAEP tends to show symmetrical alterations in primary brain stem lesions. The prolongations of interpeak latencies correspond to the brain stem segment concerned, and the same also applies to pathological amplitude reduction and deformations of individual potentials. In patients with localized brain stem damage, the reflex pathway of R2 is discussed on the basis of the BR findings. In contrast to the view held up to now that only structures situated caudal of the facial nucleus area are responsible for the genesis of the R2 response, it is assumed on the basis of our own observations that pontomesencephalic structures rostral to the facial nuclei are also important for the genesis of R2. Registration of BR and BAEP in patients with acute diffuse brain stem damage shows that both methods have a high diagnostic and prognostic value. Isolated damage and combined brain stem lesion can be demonstrated and the course can be followed up. Normalization of pathological findings reflects clinical recovery, and conversely a secondary deterioration indicates the presence of complications.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3324650 TI - The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumours. AB - The monoclonal antibody Ki-67 has been tested as a marker of proliferating cells in 52 stereotactic brain tumour biopsies. The antibody reacts with a nuclear protein expressed in G1,S, G2n and M-phases of the cell cycle. Using the immunoperoxidase technique on squash preparations the percentage of Ki-67 positive cells was determined as a fraction of the total number of tumour cells present. This Ki-67 index was in close correlation with the histological grade. Highest values were found in a pineal germinoma (46.3%) and in 3 primary cerebral non-Hodgkin lymphomas (mean 39.5%). Among the gliomas, the highest fraction of proliferating cells was seen in 2 anaplastic paediatric brain stem gliomas (mean 17.4%) and in an anaplastic ependymoma (12.5%). Anaplastic astrocytomas and glioblastomas varied considerably with mean values of 9.5% and 8%, respectively. To some extent this variability may reflect tumour heterogeneity which is more likely to manifest in small stereotactic samples than in large tissue specimens obtained during open surgery. Pilocytic astrocytomas, mixed gliomas and fibrillary astrocytomas had moderate to low percentages. Ki-67 staining of squash preparations can easily be performed on a routine basis and is, in our experience, superior to frozen sections. This method allows the determination of the growth fraction of an individual tumour and could become an important additional criterion for the decision among alternative and potentially harmful therapeutic regimens. PMID- 3324652 TI - Surgical stereotactic treatment for Gilles de la Tourette's syndrome. PMID- 3324653 TI - [Psychogenic pain: depressive changes, psychosomatic syndrome or psychobiological peculiarity? II. Etiopathogenic hypothesis]. PMID- 3324654 TI - [Neuropsychiatric manifestations of Cushing's syndrome. Report of a case]. PMID- 3324655 TI - [Separation anxiety and anxiety attack disorders ("panic disorder"). A comparative study]. PMID- 3324656 TI - The distal nephron in the kidney of fishes. PMID- 3324657 TI - Early development of the shoulder girdle and sternum in marsupials (Mammalia: Metatheria). PMID- 3324658 TI - Cognitive development and adolescent contraception: integrating theory and practice. AB - The cognitive skills that develop during adolescence are crucial to successful contraceptive practice because most birth control methods require at least a minimal ability to plan for, acquire, and utilize them at the appropriate time. Consequently, we must understand the special developmental setting in which adolescent sexual growth and experimentation occurs in order to have an impact on their contraceptive use. To provide optimal service to adolescents, the developmental and medical aspects should be taken into account in order to determine the best choice for each patient. This article demonstrates how mental health and medical providers can work together to better serve the adolescent population. PMID- 3324659 TI - Parent-adolescent conflict: an empirical review. AB - Conflict between parents and adolescents is usually seen as a normal and necessary part of human development. However, treatment approaches for problematic conflict differ depending on several variables including theoretical orientation of the clinician. This article compares and contrasts psychoanalytic, systems, and social learning theories in order to determine the empirical support for each. In addition, several issues inherent in parent-adolescent conflict are reviewed including developmental stage theory, parenting styles, peer pressures, communications skills, marital conflict, drugs, school, and sex. Several studies and reviews of the literature are examined for common conclusions. Finally, an integrated and empirically supported model to explain parent-adolescent conflict is described. PMID- 3324660 TI - Early adolescent egocentrism: a review of six articles. AB - This paper reviews six articles which appear to be representative of the past fifteen years during which researchers have focused on early adolescent egocentrism. Each article is described in chronological order and compared to research findings suggested by the other articles. Although the researchers have suggested some interesting associations, there is a lack of consistency among their findings. The author indicates methodological problems and questions for further research which arise from the reviewed articles. PMID- 3324661 TI - A psychosocial comparison of computer-mediated and face-to-face language use among severely disturbed adolescents. AB - This study analyzes the content of communications among 18 severely disturbed adolescents. Interactions were recorded from two sources: computer-based "conferences" for the group, and small group face-to-face sessions which addressed similar topics. The purpose was to determine whether there are important differences in indications of psychological state, interpersonal interest, and expressive style. The research was significant, given the strong attraction of computers to many adolescents and the paucity of research on social psychological effects of this technology. A content analysis based on a total sample of 10,224 words was performed using the Harvard IV Psychosociological Dictionary. Results indicated that computer-mediated communication was more expressive of feelings and made more frequent mention of interpersonal issues. Further, it displayed a more positive object-relations stance, was less negative in expressive style, and appeared to diminish certain traditional gender differences in group communication. These findings suggest that the computer may have an interesting adjunct role to play in reducing communication deficits commonly observed in severely disturbed adolescent clinical populations. PMID- 3324662 TI - Adolescence: a growth period conductive to alienation. AB - This paper clarifies the relationship of alienation to the period of adolescence by developing a portrait of the alienated and the at-risk adolescent. Current research on adolescent alienation follows two converging themes, the socio psychological, where deviant behavior is viewed as evidence of adolescent estrangement from self and society, and the sociological, where alienation is divided into a series of dimensions for empirical assessment. These two perspectives converge to describe the alienated adolescent. The alienated adolescent is disruptive, rebukes authority, drops out of school or becomes a passive participant, is prone to suicide, abuses drugs and alcohol, and rejects the norms established by family, school, and society in general. Adolescence is a high-risk period wherein the adolescent experiences multiple environments which exacerbates higher levels of alienation. These environments include disorganized or disruptive families, schools that encourage students to become passive participants in the learning process, and a high-pressured pace of life. To lessen the at-risk nature of adolescents toward alienation, society can take steps to humanize their environment. These steps include the intergenerational integration of adolescents, their assimilation into responsible societal activities, providing them with a sense of meaning, and enfranchisement into the decision-making process. PMID- 3324663 TI - Burckhardt Helferich 1887-1982. PMID- 3324664 TI - 13C-nuclear magnetic resonance-spectral studies of labeled glycophorins. PMID- 3324665 TI - F.A.B.-mass spectrometry of carbohydrates. PMID- 3324666 TI - The chemistry and biochemistry of the sweetness of sugars. PMID- 3324667 TI - Francisco Garcia Gonzalez 1902-1983. PMID- 3324668 TI - The circular dichroism of carbohydrates. PMID- 3324669 TI - Insulin-like activity of taurine. PMID- 3324671 TI - Immunocytochemical demonstration of taurine. AB - Amino acid immunocytochemistry represents a new and powerful tool in neuroscience. Antisera are now available to a large number of amino acids, including those that are thought to serve a transmitter role. The antiserum described here against conjugated taurine seems to be of good specificity and can be used to demonstrate taurine in the CNS as well as in other organs; in normal tissue and in experimental and pathological conditions. PMID- 3324670 TI - Taurine system in the normal and ischemic rat hippocampus. PMID- 3324672 TI - Cardiovascular pharmacology and experimental therapeutics of taurine and related compounds. PMID- 3324673 TI - From heart to hypothesis: a mechanism for the calcium modulatory actions of taurine. PMID- 3324674 TI - Molecular biology of coronavirus 1986. PMID- 3324675 TI - Regulation of pulsatile luteinizing hormone release during the estrous cycle and pregnancy in the rat. PMID- 3324676 TI - Role of prolactin in the regulation of sensitivity of the hypothalamic-pituitary system to steroid feedback. AB - During sexual maturation, pituitary gonadotropins stimulate the gonads to produce increasing amounts of biologically active steroids and yet gonadotropin release does not become suppressed until concentrations of sex hormones, LH and FSH, in peripheral circulation stabilizes at a higher adult level. There is a substantial amount of evidence that in many mammals, this transition from prepubertal to adult level of activity of the pituitary-gonadal axis is associated with a reduction in the sensitivity of the hypothalamic-adenohypophyseal system to negative feedback of gonadal steroids. In the female, these changes are accompanied by the appearance of positive estrogen feedback on gonadotropin release. In seasonal breeders, annual transitions between the periods of gonadal activity and quiescence are associated with corresponding shifts in the sensitivity to steroid feedback. Peripheral levels of pituitary prolactin (PRL) typically increase during sexual maturation and exhibit large seasonal fluctuations in response to changes in photoperiod and ambient temperature. We propose that PRL is one of the factors which regulate the sensitivity of gonadotropin release to gonadal steroid feedback. In hyperprolactinemic women, responsiveness to negative estrogen feedback increases, while LH response to positive estrogen feedback is reduced or absent. In hyperprolactinemic men, both LH and testosterone levels are reduced, implying increased sensitivity of LH release to negative testosterone feedback. In the male rat, both physiological amounts of PRL and experimentally-induced hyperprolactinemia increase the ability of exogenous testosterone to suppress LH and FSH release. Different regulatory mechanisms appear to operate in the seasonally breeding male golden hamster, in which short photoperiod causes concomitant suppression of PRL, LH, FSH and testosterone release. In this species, pharmacologic suppression of PRL release leads to increased responsiveness of plasma gonadotropin levels to negative feedback effects of testosterone, while PRL-secreting ectopic pituitary transplants exert an opposite effect. We have examined some of the suspected mechanisms of PRL modulation of testosterone feedback in male golden hamsters. In immature animals, the amount of cytoplasmic androgen receptors in the anterior pituitary was decreased by mild hyperprolactinemia and increased by treatment with bromocriptine, an inhibitor of PRL release. Bromocriptine increased pituitary androgen binding also in adult hamsters. These findings would imply that PRL modulates the responsiveness to negative steroid feedback at the pituitary level.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3324678 TI - Significance of angiogenic and growth factors in ovarian follicular development. PMID- 3324677 TI - Studies of the periovulatory interval in the in vitro perfused ovary. PMID- 3324679 TI - Kinetic aspects of follicular development in the rat. PMID- 3324680 TI - Comparative aspects of the regulation of corpus luteum function in various species. PMID- 3324681 TI - Role of placental lactogen and prolactin in human pregnancy. AB - In summary, studies from our and other laboratories strongly suggest that placental lactogen has direct effects on fetal growth and metabolism as well as on maternal metabolism. Prolactin may be important in the regulation of water and ion transport across the amnion, the production of surfactant by the fetal lung, and the immune response during pregnancy. A summary of the postulated effects of placental lactogen on maternal and fetal physiology is depicted in Figure 9 and a summary of the postulated effects of prolactin during pregnancy is shown in Table 6. Undoubtedly, future studies of the physiology of placental lactogen and prolactin will uncover new functions for these hormones during gestation. PMID- 3324682 TI - Regulation of relaxin secretion and its role in pregnancy. PMID- 3324683 TI - Spermatogenesis in vitro: searching for in vivo correlates. PMID- 3324684 TI - Hormonal regulation of Sertoli cell function. AB - The Sertoli cell is clearly influenced, directly and indirectly, by hormones. Among these are FSH, T, insulin and Vitamin A, but others may also be involved. Mechanisms are still not well understood. The biochemical effects of these hormones can be divided into quantitative and qualitative influences, with the former predominating. Specific cellular and secretory proteins and metabolites are affected, in many cases by more than one hormone. Often these same functions are influenced by other factors in the environment of the testis as well. Hormonal responsiveness of the Sertoli cell is determined in part by the maturational state of the cell. Some secreted products bind to specific cell types in the testis and epididymis and may influence the process of spermatogenesis. However, detailed mechanisms are not known at the present time. Understanding Sertoli cell function at the biochemical level and its control by hormones is clearly of key importance in understanding the control of the spermatogenic process. PMID- 3324685 TI - How does the gonad affect LHRH secretion? Effects of gonadectomy on LHRH release from median eminence nerve terminals incubated in vitro and on LHRH concentration in hypophyseal portal blood. PMID- 3324686 TI - Orchidectomy induces temporal and regional changes in the synthesis and processing of the LHRH prohormone in the rat brain. PMID- 3324687 TI - LH and estradiol secretion after HCG and GNRH treatments in gilts. PMID- 3324688 TI - The steroid-neuropeptide connection in the control of LHRH secretion. PMID- 3324689 TI - On the site of action of the estradiol-induced release of luteinizing hormone (LH) in pigs. PMID- 3324690 TI - Ovarian and decidual relaxins in human pregnancy. PMID- 3324691 TI - Protein F1 and protein kinase C may regulate the persistence, not the initiation, of synaptic potentiation in the hippocampus. PMID- 3324692 TI - Electrophysiologic responses and adenylate cyclase activities of mouse spinal cord-dorsal root ganglion explants rendered tolerant by chronic exposure to morphine or pertussis toxin. PMID- 3324693 TI - Cytoskeletal pathology in neurodegenerative diseases. PMID- 3324694 TI - Polyunsaturated fatty acids and inositol phospholipids at the synapse in neuronal responsiveness. PMID- 3324695 TI - Molecular genetics of development. Dedicated to Ernest W. Caspari. PMID- 3324696 TI - Ernst W. Caspari: geneticist, teacher, and mentor. PMID- 3324697 TI - Heat-shock proteins and development. AB - At the simplest level there is little doubt that the heat shock response is homeostatic, to protect the cell against the ravages of the environmental insult and ensure that the cell can continue its normal life after the crisis has passed. PMID- 3324698 TI - Developmental control and evolution in the chorion gene families of insects. PMID- 3324699 TI - The significance of split genes to developmental genetics. PMID- 3324700 TI - Gene transfer into mice. PMID- 3324702 TI - The molecular basis of the evolution of sex. AB - Traditionally, sexual reproduction has been explained as an adaptation for producing genetic variation through allelic recombination. Serious difficulties with this explanation have led many workers to conclude that the benefit of sex is a major unsolved problem in evolutionary biology. A recent informational approach to this problem has led to the view that the two fundamental aspects of sex, recombination and outcrossing, are adaptive responses to the two major sources of noise in transmitting genetic information, DNA damage and replication errors. We refer to this view as the repair hypothesis, to distinguish it from the traditional variation hypothesis. On the repair hypothesis, recombination is a process for repairing damaged DNA. In dealing with damage, recombination produces a form of informational noise, allelic recombination, as a by-product. Recombinational repair is the only repair process known which can overcome double strand damages in DNA, and such damages are common in nature. Recombinational repair is prevalent from the simplest to the most complex organisms. It is effective against many different types of DNA-damaging agents, and, in particular, is highly efficient in overcoming double-strand damages. Current understanding of the mechanisms of recombination during meiosis suggests that meiosis is designed for repairing DNA. These considerations form the basis for the first part of the repair hypothesis, that recombination is an adaptation for dealing with DNA damage. The evolution of sex can be viewed as a continuum on the repair hypothesis. Sex is presumed to have arisen in primitive RNA-containing protocells whose sexual process was similar to that of recombinational repair in extent segmented, single-stranded RNA viruses, which are among the simplest known organisms. Although this early form of repair occurred by nonenzymatic reassortment of replicas of undamaged RNA segments, it evolved into enzyme mediated breakage and exchange between long DNA molecules. As some lines of descent became more complex, their genome information increased, leading to increased vulnerability to mutation. The diploid stage of the sexual cycle, which was at first transient, became the predominant stage in some lines of descent because it allowed complementation, the masking of deleterious recessive mutations. Out-crossing, the second fundamental aspect of sex, is also maintained by the advantage of masking mutations. However, outcrossing can be abandoned in favor of parthenogenesis or selfing under conditions in which the costs of mating are very high.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3324701 TI - Mechanisms of heat-shock gene activation in higher eukaryotes. PMID- 3324703 TI - Regulatory gene action during eukaryotic development. PMID- 3324704 TI - Potassium supplementation lowers blood pressure in spontaneously hypertensive rats--relationships with urinary prostaglandins and renin. AB - Supplementation with 1% KCl significantly attenuated the blood pressure rise normally observed in SHR's with increasing age. Urine volume and urinary excretions of sodium, potassium and 6-keto-PGF1 alpha were significantly elevated in those animals receiving potassium. Plasma renin activity measured at the end of the study was significantly reduced in potassium supplemented animals compared to controls. PMID- 3324705 TI - Effect of pregnancy on plasma renin activity and glomerular synthesis of prostaglandins and thromboxane in rats. AB - Normal pregnancy in women and rats is characterized by an increased glomerular filtration rate. Because prostaglandin glomerular synthesis has been reported to be increased in 2 other circumstances with glomerular hyperfiltration (streptozotocin-induced diabetes and high protein dietary intake in Heymann nephrilis), we studied prostaglandin biosynthesis in glomeruli obtained from pregnant Wistar rats in comparison with non pregnant rats during the estrus cycle. Comparatively to the 3 first phases of the cycle, and wether or not arachidonic acid was present, PGE2 and PGF2 alpha production rates were found significantly higher in diestrus 2 (2-3 fold increase for both) at 15 days of pregnancy (2 fold increase for PGE2, 5-6 fold increase for PGF2 alpha) and at 21 days of pregnancy (5-6 fold increase for both). On the other hand synthesis of TXB2 was not increased during pregnancy nor during diestrus 2. Plasma renin activity (PRA) was increased during pregnancy. It is concluded that in presence of increased PRA, the increased synthesis of PGE2 may be the hormonal factor explaining, at least in part, the hemodynamic mechanism of glomerular hyperfiltration which has been previously described by micropuncture techniques and characterized by increased renal plasma flow, increased glomerular filtration pressure and decreased ultrafiltration coefficient. PMID- 3324706 TI - Reduced excretion of vasodilator prostaglandins in preeclampsia. AB - The role of prostaglandin (PG) system in preeclampsia (pre-E) was investigated. Urinary excretion of PGE2,6-keto PGF1 alpha,2,3 dinor 6-keto PGF1 alpha, TxB2 and 2,3-dinor-TxB2 and kallikrein were determined in 10 normotensive pregnant women and 14 with pre-E. 6-keto PGF1 alpha and 2,3-dinor 6-keto PGF1 alpha (the main renal and extrarenal metabolites of vasodilator PGI2) and PGE2 excretion was lower in pre-E. TxB2 metabolites in urine were similar in the two groups of women. Our data are consistent with the hypothesis of an imbalance between vasodilator and vasoconstrictor PGs in pre-E. PMID- 3324707 TI - Inhibition of prostaglandins and angiotensin II: effects on renal function in hypertensive patients. PMID- 3324708 TI - Humoral changes during a long-term antihypertensive treatment. PMID- 3324709 TI - Renal production of prostaglandin E2 is not deficient in essential hypertension. PMID- 3324710 TI - Interactions of renal prostaglandins, renin-angiotensin system and renal kallikrein-kinin system in human hypertension. AB - Dietary sodium deprivation lowered blood pressure in patients with essential hypertension, while indomethacin induced a rise in blood pressure with significant decreases in plasma angiotensin II concentration and urinary excretion of sodium and PGE. In contrast, captopril lowered blood pressure in them with significant decrease in plasma angiotensin II concentration and significant increase in urinary excretion of sodium and PGE. These data strongly indicate that the decreased PG generation in the nephron could elevate blood pressure by means of sodium retention caused by the reduced renal excretory function in spite of the decreased R-A system in human, suggesting the involvement of renal tubular PGE2 in the regulation of blood pressure. PMID- 3324711 TI - The pathophysiological role of renal dopamine, kallikrein kinin and prostaglandin systems in essential hypertension. AB - In order to clarify the relationship and the pathophysiological role of renal dopamine, kallikrein-kinin and prostaglandin systems in essential hypertensives, the effects of dopamine on these systems and renal sodium handling were investigated. Basal levels of kallikrein, kinin and prostaglandin E2 in essential hypertensives were significantly lower than those in normotensives. Those of kallikrein and kinin were obviously more suppressed in the low renin group than in the normal renin group, but no significant difference in prostaglandin E2 was found in either subgroup. Urinary dopamine excretion was significantly lower in the low renin essential hypertensives, while no significant difference was found between normotensives and normal renin essential hypertensives. Kallikrein activity and prostaglandin E2 were significantly increased in essential hypertensives by dopamine infusion, and no significant difference was found in kallikrein-quantity and kinin between normotensives and essential hypertensives after the infusion. These increases of kallikrein and kinin were significantly higher in the low renin group than in normal renin group, but those of prostaglandin E2 were not. Urine volume, urinary sodium excretion and fractional excretions of sodium and inorganic phosphorus were all increased in both normotensives and essential hypertensives after dopamine infusion. The increases of these were significantly greater in essential hypertensives than in normotensives, and greater in the low renin group than the normal renin group. From these results, it was suggested that the dopamine, kallikrein-kinin and prostaglandin E2 system have a close relationship with each other, and the suppression of these systems may contribute to the pathophysiology of essential hypertension, especially in the low renin group. PMID- 3324712 TI - Relationship between urinary kallikrein excretion and the extent of circulating inactive renin activation by the kidney. PMID- 3324713 TI - Measurement of circulating kinins, their changes by inhibition of kininase II and their possible blood pressure lowering effect. PMID- 3324714 TI - Diminution by captopril of the diuretic, natriuretic and kallikrein stimulating action of furosemide by reduction in its renal secretion. AB - The effect of furosemide (40 mg iv) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated without and with pretreatment by captopril (100 mg po). Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly (UNaV pre-C: +15, 1 +/- 2.1 ml/min vs. post-C: 7.0 +/- 0.3 ml/min; p less than 0.001). Similar changes in urinary kallikrein and kinin excretion were observed after captopril pretreatment, but because of the great coefficient of variation these changes did not reach statistical significance. The reason for the reduced activity of furosemide after captopril pretreatment was the diminished proximal-tubular secretion of furosemide, as it could be shown by direct measurement of the drug in urine. After furosemide injection changes in plasma aldosterone concentration paralleled changes in renal kallikrein and kinin excretion. However, after captopril there was a sharp dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. PMID- 3324715 TI - Urinary kallikrein excretion can predict the blood pressure response to a single oral dose of captopril. AB - The antihypertensive efficacy of ACE inhibitors depends in theory from the blockade of the angiotensin II formation but also from the inhibition of kinin breakdown. To test whether a blunted activity of the kallikrein-kinin system might account for the failure of ACE inhibitors in lowering BP in patients in whom the renin-angiotensin system is not enhanced, thirty-one essential hypertensives with normal or low PRA were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall both in systolic and diastolic blood pressure (BP) was obtained in the subgroup of patients who were classified as "normal kallikrein hypertensives" according to whether their pretreatment urinary kallikrein excretion was within the normal range, while no significant change in BP was observed in "low kallikrein hypertensives". Furthermore the mean percentage fall in mean BP, throughout the 2 hours following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47, p less than 0.05) in the entire group of patients. Our results suggest that a blunted activity of the kallikrein system might be responsible for failure of captopril in lowering BP in patients in whom the renin-angiotensin system is not pathogenetically implicated. PMID- 3324716 TI - Low urinary excretion of active and total kallikrein in developing spontaneously hypertensive rats and effect of long term converting enzyme inhibition. PMID- 3324717 TI - Lack of a role of circulating bradykinin in the blood pressure response to acute angiotensin converting enzyme inhibition in rats. AB - The role of circulating bradykinin in blood pressure regulation was investigated in conscious normotensive rats using a competitive antagonist of bradykinin. The acute blood pressure effect of this antagonist was also evaluated after inhibition of angiotensin converting enzyme with captopril and during simultaneous infusion of exogenous angiotensin II. No evidence was found for a role of circulating bradykinin in rats studied under normal conditions. Endogenous bradykinin seemed however involved in blood pressure control during angiotensin II infusion. Acute angiotensin converting enzyme inhibition had no influence on the blood pressure response to the bradykinin antagonist. PMID- 3324718 TI - Inhibitory effect of sulindac on prostaglandin synthesis in cultured renal and vascular cells. AB - Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is said to be less toxic to the kidney than the other NSAIDs. To examine this hypothesis we investigated the effects of sulindac and other NSAIDs on prostaglandin (PG) synthesis in cultured rat renal and vascular cells. In all cells examined, indomethacin, tiaprofenic acid, aspirin and ibuprofen (3.3 x 10(-5)-3.3 x 10( 4)M) inhibited both basal and arachidonic acid (AA)-stimulated PGE2 or PGI2 synthesis (measured as 6-keto-PGF1 alpha), while sulindac (3.3 x 10(-5)-3.3 x 10( 4)M) inhibited both basal and AA-stimulated PGE2 synthesis in renal papillary collecting tubule cells but not basal PGI2 synthesis in vascular smooth muscle cells or AA-stimulated PGE2 synthesis in glomerular mesangial cells. The order of potency for NSAIDs to inhibit PG synthesis in these cells was tiaprofenic acid, indomethacin greater than ibuprofen, aspirin greater than sulindac. It is suggested that the prodrug sulindac is biotransformed to the active sulfide in the intact kidney cells, which may be less prominent in glomerular mesangial or vascular smooth muscle cells. PMID- 3324719 TI - Effect of in vitro aging on prostaglandin synthesis in cultured rat vascular smooth muscle cells. AB - Cultured rat vascular smooth muscle cells from mesenteric artery produced prostaglandin (PG)E2, PGF2 alpha, PGI2 and thromboxane (TX)A2 in response to arachidonic acid, calcium ionophore A23187, vasopressin and angiotensin II. PGI2 was the major product among these PGs. PG synthesis in these cells decreased with in vitro aging, but the distribution pattern of PG synthesis did not change up to the passage level 56. Therefore, it is suggested that imbalance among PGs may not be directly implicated in vascular diseases in aging. PMID- 3324720 TI - Vasodepressor lipid of the renomedullary interstitial cells of the renal papilla is a prohormone activated by the liver. PMID- 3324721 TI - A double blind clinical trial of Tigason (Ro 10-9359) versus placebo in psoriasis. PMID- 3324722 TI - Diagnosis, treatment and complications of appendicitis in childhood. A critical review of 3,514 cases.I. Problems of appendicitis in childhood--classification and methods of study. PMID- 3324723 TI - Diagnosis, treatment and complications of appendicitis in childhood. II. Special features in the diagnosis of different forms of appendicitis in children. PMID- 3324724 TI - Diagnosis, treatment and complications of appendicitis in childhood. III. Surgical and general treatment of appendicitis. PMID- 3324725 TI - Diagnosis, treatment and complications of appendicitis in childhood. IV. Postoperative complications of appendicitis. PMID- 3324726 TI - Pharmacotherapy of the postirradiation haemorrhagic syndrome. PMID- 3324727 TI - Comparison of the blood clotting mechanisms in man and some common laboratory animals. PMID- 3324728 TI - Postirradiation haemorrhagic syndrome in man. PMID- 3324729 TI - The influencing of thrombocytopoiesis with irradiation. PMID- 3324730 TI - Postirradiation changes in blood platelet counts. PMID- 3324732 TI - The disorder of the blood platelet reaction with vessel wall after irradiation. PMID- 3324731 TI - Postirradiation morphological, functional and biochemical changes of the blood platelets. PMID- 3324733 TI - Postirradiation changes of plasma coagulation factors and inhibitors of coagulation. PMID- 3324734 TI - The postirradiation changes of fibrinolytic system. PMID- 3324735 TI - Postirradiation changes of the kinin system. PMID- 3324736 TI - The substitution therapy of the postirradiation syndrome with transfusion preparations. PMID- 3324737 TI - [Transrectal longitudinal ultrasonography of the prostate by electronic linear scanning (1)]. AB - Transrectal longitudinal ultrasonography of the prostate was done for 20 patients with prostatic diseases, 12 with benign prostatic hypertrophy, 6 with bladder neck contracture, and 2 with chronic prostatitis. The intravesical protrusion of the prostate and the opening of the bladder neck, which can be easily recognized by this method, were discussed in relation to dysuria, using subjective symptoms, residual urine, and uroflowmetry (peak flow rate) as parameters. The former was slightly correlated to dysuria, and the latter was definitely correlated to dysuria. PMID- 3324738 TI - [Rhabdomyosarcoma of the kidney: report of a case]. AB - A case of rhabdomyosarcoma of the right kidney is presented. A 78-year-old man was admitted with the complaint of abdominal pain and abdominal fullness on March 15, 1985. Radiological examination showed a giant tumor of the right kidney. Radical nephrectomy and right hemicolectomy were performed. Histological findings were embryonal rhabdomyosarcoma of the kidney. Residual tumor in the duodenal area recurred and he died of peri-duodenal abscess 2 months after admission. This case is the 17th case of rhabdomyosarcoma of the kidney in Japan. The literature is reviewed and discussed. PMID- 3324739 TI - [A case of inverted papilloma of the ureter with malignant findings]. AB - A 70-year-old female with inverted papilloma of the ureter is presented. She was hospitalized because of asymptomatic macrohematuria. Excretory urography and retrograde pyelography demonstrated a filling defect with smooth contour at the mid-portion of the right ureter. Abdominal computer tomographic (CT) scan showed mass lesion (CT number 41) at the same portion as the filling defect. She was diagnosed as having an ureteral tumor and right nephroureterectomy was performed. The gross specimen contained a 24 X 12 mm, polypoid, pedunculated and smooth surfaced tumor. Pathological diagnosis was inverted papilloma. However, microscopic examination revealed a malignant finding corresponding to transitional cell carcinoma grade 1. From the Japanese and foreign literature, 25 cases of ureteral inverted papilloma were collected and are reviewed. Clinical and pathological features are discussed. PMID- 3324740 TI - [Inverted papilloma of the ureter]. AB - Two cases of ureteral inverted papilloma are reported. Case 1: A 48-year-old male had asymptomatic gross hematuria and filling defect of left middle ureter on intravenous pyelography. Segmental resection of ureter was performed. The specimen was a 1 cm polypoid lesion with histologic features resembling "multifocal bud-like proliferation", which was reported as the initial stage of the inverted urothelial tumor by Kunze et al. Case 2: A 64-year-old female with asymptomatic gross hematuria and complete obstruction of left middle ureter on ante- and retrograde pyelograms. Total nephroureterectomy was performed. A 4 cm lobulated and pedunculated lesion with histologic features of typical inverted urothelial papilloma was resected. Twenty-one cases of ureteral inverted papilloma in the literature, including our cases, are analyzed. PMID- 3324741 TI - [Recurrence of transitional cell carcinoma in the left pelvis and ureter, and ileal conduit after total cystectomy: a case report]. AB - A 63-year-old male with transitional cell carcinoma of the bladder underwent total cystectomy. Five years later sequential excretory urography and urinary cytologic examination revealed tumor recurrence in the left pelvis and ureter; left nephroureterectomy was performed in July, 1984. In December, 1985, he complained of macrohematuria and urinary cytology was positive. Ileal conduitgraphy showed filling defects at the bilateral uretero-ileal anastomosis, where two papillary lesions were disclosed by endoscopic examination. In January, 1986, total extirpation of the ileal conduit and reconstruction of a new ileal conduit was performed. Macroscopically the two lesions were found to be a papillary tumor at left uretero-ileal anastomosis and a polypoid tumor distal to right uretero-ileal anastomosis. Histological examination revealed both tumors to be grade II transitional cell carcinoma. This rare case is discussed and the literature is reviewed. PMID- 3324742 TI - [A rare case of adenocarcinoma of the bladder following ileocystoplasty]. AB - This is a report of a case of well-differentiated adenocarcinoma found 14 years after ileocystoplasty. Total cystectomy and right ureterocutaneostomy were performed, and the origin of this tumor was proved to be the ileal part of ileocystoplasty. This is a rare case of adenocarcinoma in the ileal part of ileocystoplasty, because a review of the literature revealed only three other such cases. PMID- 3324743 TI - [Seminal vesicle cyst associated with ipsilateral renal agenesis]. AB - A case of seminal vesicle cyst associated with ipsilateral renal agenesis was experienced recently in our clinic. A 23-year-old male presented with a complaint of right hemiscrotal pain. Right kidney was not visualized by excretory urography. Cystoscopic examination revealed the absence of the right half of trigone and the right posterolateral wall bulging into the bladder, suggestive of an extrinsic mass displacing the bladder wall. Ultrasonography and computerized tomographic scan showed a large cystic mass in the right side of the retrovesical region. Exploratory operation disclosed that the cystic mass was part of the dilated seminal vesicle. Seminal vesiculectomy was done. Many cases of seminal vesicle cyst are associated with a simple or complex malformation of ipsilateral upper urinary tract (renal agenesis, dysplasia, hypoplasia and ectopic ureter). We speculate that most of the benign seminal vesicle cysts are formed as a congenital anomaly due to defective mesonephric duct development which causes concomitant malformations in the upper urinary tract. PMID- 3324744 TI - [Mesh-graft urethroplasty: a case report]. AB - We used a meshed free-foreskin transplant in a two-stage procedure for reconstruction of the extended stricture of urethra after direct vision urethrotomy. The results were excellent. Mesh-graft urethroplasty is a useful method for patients with extended strictures of the urethra or recurrent strictures after several operations. PMID- 3324745 TI - A case of penile tumor: combination of leiomyosarcoma and squamous cell carcinoma. AB - Leiomyosarcoma of the penis is a very rare malignant tumor. We describe a patient with a combination of leiomyosarcoma and squamous cell carcinoma, apparently the first case in the world, and review previous cases of leiomyosarcoma. PMID- 3324746 TI - Spermatocytic seminoma: a case report. AB - An 81-year-old man with a painless enlargement of the right testis which developed 11 years ago was treated with right orchiectomy without any combined therapy in 1981. This tumor pathologically proved to be spermatocytic seminoma. The patient has been well and has shown no evidence of recurrence for the past 5 years. PMID- 3324747 TI - [A case of giant obsolete hydrocele testis]. AB - A 58-year-old man visited the urological clinic in Prefectural Tohkamachi Hospital with complaint of swelling of bilateral scrotal contents. He had no history of fever, pain or difficulty of urination. Physical examination revealed a giant mass of adult-head size in right scrotum and left inguinal hernia of fist growth. Surgical extirpation of the right scrotal mass and left inguinal herniorrhaphy was performed and the mass was diagnosed as obsolete hydrocele testis and weighed 1,600 g. The excised hydrocele sac showed marked thickening and dark brown pus amounted to about 1,400 ml, which was negative in bacterial culture. Histological examination revealed partial deposits of cholesterol and calcification in tunica vaginalis with extremely atrophic testis and destructive spermatogenesis. The findings suggested the existence of long-term infection in hydrocele testis. The etiology and pathogenesis of this disease is discussed. PMID- 3324749 TI - Spontaneous relapse of late onset group B streptococcal septicemia. PMID- 3324748 TI - Glucagon, insulin and the thyroid. PMID- 3324751 TI - Subpoenas and discovery of pharmacy records. PMID- 3324750 TI - Computer assisted instruction with deaf children: panacea, placebo or poison? PMID- 3324752 TI - Charles Norris (1868-1935) and Thomas A. Gonzales (1878-1956), New York's forensic pioneers. AB - American forensic medicine is forever indebted to pioneers like George Magrath of Boston, Milton Helpern of New York, LeMoyne Snyder of Michigan, and others, but the organizing of forensic medicine in the formal sense is due to the efforts of Charles Norris (Figure 1) and his successor Thomas A. Gonzales (Figure 2). These men were instrumental in developing the subspecialty as an extension of clinical medicine in which information derived from study of the dead was applied to benefit the living. Their combined efforts between 1918 and 1954 represent the epitome of the application of scientific expertise to medicolegal investigation of deaths in America. Their collaboration from 1918 to 1935 was particularly fruitful. The support of Dr. Alexander Gettler and, in 1938, the addition of Dr. Wiener to the Office of the Chief Medical Examiner made this period a golden era for forensic medicine. PMID- 3324753 TI - Forensic medicine in Great Britain. II. The origins of the British medicolegal system and some historic cases. AB - The British medicolegal system, which today is largely based on the Coroner's Act of 1887, developed slowly, beginning with the election of county coroners in the 12th century. The duties of the medieval coroner included the collection of revenues due to the Crown, recordkeeping, presiding over inquests, and overseeing juries in cases of sudden or unnatural death. However, by the 14th century, the influence of the coroner had diminished and the office fell into disrepute. The practice of forensic medicine in the United Kingdom can be dated from the 17th century, when the first autopsy was recorded. However, the first original textbook on this subject did not appear in Britain until the early 19th century. Around the same time, due to a wave of homicidal poisonings, toxicology emerged as an important discipline. A number of historical cases of homicidal poisoning, as well as several cases of homicide by external wounding, are discussed herein. In the present day, with the passage of various laws, the British coroner deals only with sudden and unnatural death and treasure trove. PMID- 3324754 TI - Evaluation of epidemiologic approaches to the study of lung disease related to cotton dust exposures. AB - Epidemiologic approaches to improved understanding of the several reactions observed in cotton processors began in 1955 with Schilling's symptom classification of Monday-morning chest tightness. To date, epidemiologic studies have identified the importance of increasing years of exposure to the development of both specific and nonspecific chronic respiratory symptoms and of acute change in pulmonary function. The few longitudinal studies suggest similar associations with accelerated loss of pulmonary function. Respirable dust level has been associated, cross-sectionally, with symptoms and with acute function change, but studies have not yet been made with sufficient prospective collection of both exposure and health effects data to estimate accurately the association of continued exposure with accelerated loss of lung function or development of disability. Furthermore, there has been very limited field study comparing exposure to respirable dust distinguished from exposure to endotoxin. With careful attention to features of study design and analytic plans, investigators can take advantage of simple technology to examine the fate of the acute responder, the potential for recovery if exposure is reduced or ceased, and the long-term dose response relationship between different cumulative measures of exposure and chronic disease. PMID- 3324756 TI - Objectives for health monitoring and surveillance. AB - A properly designed respiratory disease monitoring and surveillance program for the effects of cotton dust uses tools similar to those used clinically but provides a different focus--the potential for disease prevention in individuals and the control of excess exposures in groups. Both surveillance and monitoring require the use of standard instruments (questionnaires and pulmonary function equipment) with careful attention to equipment calibration and standard methods for administering tests. Monitoring focuses on the individual to identify early evidence of disease and to detect those subjects who are susceptible even under usually well controlled exposure circumstances. Surveillance is successful when designed to collect information at regular intervals (based on type and level of exposure and previously measured response) and the results are interpreted according to reasonably rigorous criteria. A major additional component is the examination of surveillance results according to groups based on job, exposure, work tenure, and other risk factors (e.g., smoking). PMID- 3324755 TI - The role of endotoxin for reactions after exposure to cotton dust. AB - Gram-negative bacteria and their endotoxins are present on all parts of the cotton plant and occur in large numbers after rain or frost. Endotoxins activate pulmonary macrophages that in turn recruit neutrophils into the airways. Platelets accumulate in pulmonary capillaries. The presence of these cells allows for the initiation of acute and chronic inflammation. Dose-response relationships have been demonstrated between endotoxin and fever, chest tightness, and reduction in air flow (bronchoconstriction) in cotton workers. Limited data suggest that after cotton dust exposure, other symptoms, such as airway hyperreactivity and chronic inflammation, are also related to the endotoxin exposure. Tentative thresholds for airborne endotoxins are presented. PMID- 3324757 TI - Current trends in research on the etiology and pathogenesis of byssinosis. AB - The features of the cotton dust syndrome which need to be considered when formulating a hypothesis on mechanism(s) are: 1) the presence of fever, 2) the "Monday effect," 3) the slow onset of forced expiratory volume in 1 second (FEV1) changes, and 4) the presence of bronchitis in chronic sufferers but the absence of emphysema or fibrosis. The main hypotheses concerning the mechanisms are direct release of histamine triggered by cotton dust components, immune reactions (principally antibody mediated) to cotton dust antigens, and inflammatory response(s) triggered by endotoxins released from bacterial contaminants on the dust. While histamine release and immune reactions may occur as a result of cotton dust inhalation, it is suggested that they are of secondary importance in comparison to inflammation. Evidence is reviewed that implicates bacterial lipopolysaccharide (LPS) present in the dust as the principal etiologic agent in this process. It is postulated that LPS inhalation stimulates a secretory response by lung macrophages, involving the release of effector molecules which trigger coagulation, bronchoconstriction, fever, and mucus production. LPS induced macrophage secretory products also promote the local sequestration and activation of both neutrophils and platelets, which serve to amplify the inflammatory response. Evidence is presented implicating both interstitial and alveolar macrophages in this process. The problems associated with the identification of "high risk" groups of cotton workers will be discussed, from a number of viewpoints; consideration will be given to the role of a variety of environmental factors (including tobacco smoking) in this context, as well as possible genetic factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324758 TI - Strategies for prevention of byssinosis. AB - Cotton dust is a heterogeneous mixture of plant parts and contaminants from the soil, weeds, and microorganisms. Research to control byssinosis has focused on methods to reduce the trash associated with harvested fiber and control the dust in the textile mill environment. Dust control has been effective in reducing the prevalence of byssinosis, but because cotton dust is a heterogeneous mixture of components, simple reduction in dust levels does not always assure the prevention of byssinosis. Research to identify the agents that cause byssinosis and development of methods to eliminate those agents from cotton is needed to prevent new cases of byssinosis. PMID- 3324759 TI - Some opinions on byssinosis in China. AB - On the basis of some study results in China and reports from abroad, a conclusion should be drawn that leads to the recognition of a pneumoconiosis-like lesion of interstitial fibrosis. This disease is called "cotton pneumoconiosis" and we may classify these occupational lesions into four types: 1) byssinosis; 2) chronic obstructive pulmonary disease (COPD); 3) cotton fever; and 4) cotton pneumoconiosis. Byssinosis, COPD, cotton fever and cotton pneumoconiosis may be different types of responses due to the different duration of exposure, the different parts of bronchial tree (upper respiratory tract, small airway, and respiratory part) where deposition occurs, and the different components of cotton dust (broken cotton fibers, bracts, pericarps, bacteria, and fungi). These responses, which include histaminelike reaction, allergy, and stimulation of foreign material, happen in different symptoms of the syndrome among cotton mill workers. But no matter whether responses caused by inhalation of dust are inflammation or allergic reaction, cotton dust is foreign stimulation on deposited sites, causing lung fibrosis after lung stimulation. For the health of cotton workers, we must pay attention not only to the acute effects but also to the chronic lesions. We therefore suggest that these four types of occupational lung disorders caused by inhalation of cotton dust may be called by the joint name, "Byssinosis syndrome." PMID- 3324760 TI - Self-instruction, individual differences, and mental retardation. AB - A general theoretical framework to guide research on self-instructional training was presented. The theory emphasizes that in evaluating self-instructional programs, more attention must be given to the developmental characteristics of the persons to be trained and suggests that self-instruction will be particularly useful to young nonretarded children, mentally retarded persons, and, more generally, individuals who have limited linguistic skills and a limited knowledge base. Further, retarded children taught to self-instruct will show better attention, memory, and motivation and manifest less impulsive behavior, maladaptive perseveration, and field dependency when taught through a self instructional in contrast to an external instructional format. Empirical support for this theory was examined and recommendations for future research made. PMID- 3324761 TI - Acetate metabolism during hemodialysis: metabolic considerations. AB - Acetate is used during regular hemodialysis to replace the bicarbonate lost during dialysis. The temporal changes of plasma bicarbonate and acetate concentrations and the critical role of acetate metabolism for the maintenance of plasma bicarbonate are described. We point out that the maximal rate of acetate oxidation in man is usually reached during dialysis, and we identify physiologic and pathologic factors that may modify this Vmax. A syndrome of 'intolerance to acetate' has been described. This syndrome is analyzed in the light of the metabolic consequences of a rapid flux of acetate oxidation in liver and muscle cells. More specifically, the effects of rapid acetate metabolism on tissue ATP, CoA, adenosine and other ATP degradation products are presented. The possible impact of dialysis-induced depletion of carnitine on optimal acetate metabolism is discussed. The potential clinical consequences produced by these changes are presented in relation to the symptoms sometimes observed during dialysis against acetate: vasodilation, hypotension and angina pectoris. The hypoxemia induced by acetate is also briefly reviewed. Different directions are proposed for future research. PMID- 3324762 TI - False-positive digoxin measurements due to conjugated metabolite accumulation in combined renal and hepatic dysfunction. AB - A 41-year-old man with combined renal and hepatic dysfunction was noted to have marked elevations in serum digoxin concentration subsequent to the discontinuation of digoxin therapy. These elevations (peak value 8.6 ng/ml), as measured by both radioimmunoassay and fluorescence polarization immunoassay, were not associated with electrocardiographic evidence of digitalis toxicity. Using a combined high-performance liquid chromatography/radioimmunoassay, accumulation and immunoassay cross-reactivity of conjugates of digoxigenin monodigitoxoside (cardioinactive metabolites of digoxin) were found to be the basis of the observed false elevation in digoxin concentration. PMID- 3324763 TI - Renal transplantation in systemic lupus erythematosus: one center's experience. AB - A retrospective analysis of 15 renal transplant patients with end-stage renal disease (ESRD) secondary to systemic lupus erythematosus (SLE) was performed. Overall actuarial patient and graft survival at 6 years was 93 and 84%, respectively. Recipients of HLA-identical kidneys did not appear to be at increased risk of allograft failure due to rejection or recurrent disease. Two biopsy-proven cases of recurrent lupus involving the allograft were observed and are discussed. Those patients currently experiencing excellent graft function (creatinine less than 2 mg/dl) had a significantly longer pretransplantation dialytic interval than the group whose most recent serum creatinine exceeds 2 mg/dl (or returned to dialysis). Posttransplantation monitoring of antinuclear antibody, antidouble-stranded DNA, C3, C4, and circulating immune complexes was not predictive of renal or extrarenal disease activity. Renal transplantation should be considered an excellent therapeutic modality for the lupus patient with ESRD, although an interim period on dialysis of at least 1 year seems warranted. PMID- 3324764 TI - Primary renal artery dissection. Presentation of two cases and brief review of the literature. AB - Two cases of primary renal artery dissection in caucasian males, aged 40 and 37 years, respectively, are presented. In both subjects, the clinical picture disclosed renal infarction with transient deterioration of renal function, microhematuria and proteinuria. In 1 patient, a slight, temporary increase in blood pressure was also observed. Both men experienced contralateral relapse 12 days and 7 years, respectively, after the first episode. The diagnosis was based on characteristic (case 1) or suggestive (case 2) arteriographic findings. In 1 subject, control arteriography suggested some progression of the lesion. Both patients were treated conservatively. A comparison with 143 cases previously reported worldwide emphasizes some aspects of this 'not-so-rare' entity. PMID- 3324765 TI - Meningitis due to Campylobacter fetus intestinalis in a kidney transplant recipient. A case report. AB - A 47-year-old man developed Campylobacter fetus intestinalis meningitis 3 years after cadaver renal transplantation. The infection was successfully controlled with chloramphenicol followed by erythromycin. There were no relapses during the past 5 years and the allograft function remains normal. The available evidence suggests that the campylobacter sepsis was associated with nutritional therapy, the patient received in a Mexican clinic. The present case is reported because of its clinical importance and epidemiological implications. PMID- 3324766 TI - Renal physiology of the prostaglandins and the effects of nonsteroidal anti inflammatory agents on the kidney. AB - The prostaglandins are a series of fatty acid products derived from the cellular metabolism of arachidonic acid. The kidney makes prostaglandins and the endogenous renal prostaglandins appear to play a role in the regulation of renal hemodynamics, renal salt and water excretion, and control of the level of activity of the renin-angiotensin system. The administration of nonsteroidal anti inflammatory drugs blocks cyclooxygenase activity, an early step in the synthesis of prostaglandins. This class of drugs, under certain circumstances, leads to sodium retention, hyperkalemia and several different forms of acute and chronic renal failure. The potential role of altered prostaglandin synthesis in leading to these clinical syndromes is reviewed. PMID- 3324767 TI - Occupational therapy in mental health: crisis or opportunity? AB - For at least a decade, concern has been expressed about the status of occupational therapy in mental health. Increases in the number of new jobs and clinicians have not kept pace with growth in other practice areas. Although growing criticism of the practice of deinstitutionalization and an increased focus on cost-effectiveness have recently become major public policy trends in mental health practice, the psychological and nursing professions have responded creatively in order to expand their influence and practice. This paper relates changes in the delivery of mental health services to the systematic study of policy development and careful planning needed to help occupational therapy accomplish the same goals. PMID- 3324769 TI - Homograft ossiculoplasty: long-term results. AB - The use of homograft ossicles and homograft cortical bone has been common practice in chronic ear surgery for reconstruction of the interrupted ossicular chain. However, the possibilities of extrusion, reabsorption, and necrosis of these homografts have jeopardized the fate of such tissue for ossicular reconstruction. This study analyzes the fate of more than 400 homograft ossicles and bone columellas used for ossicular chain reconstruction over more than fifteen years, all of which were previously processed and sculptured in an ear bank. Many of these homografts have been observed for longer than five years. Histologic findings in longstanding homograft ossicles in the middle ear are presented. PMID- 3324768 TI - External electrical tinnitus suppression: a review. AB - Our experience with transcutaneous electrical stimulation for tinnitus suppression has been with the Theraband Headset from Audimax Inc. The purpose of this article is to review the highlights of the patients who exhibited tinnitus suppression and/or tinnitus control, and to provide an update of our results and techniques using external electrical stimulation with prolonged stimulation (stage IV). Patient selection is considered critical to the success of external electrical stimulation for tinnitus suppression. The key elements include the clinical finding of a peripheral site of lesion of the tinnitus; positive maskability of the symptom of tinnitus; absence of active ear disease; absence of a vestibular asymmetry; and absence or minimal evidence of dysfunction of the central auditory system. The protocol described for patient selection allows for tinnitus identification, the differentiation of clinical tinnitus types, and the clinical application of the concept of the dynamic range of electrical tinnitus suppression. External electrical tinnitus suppression is believed effective in a limited number of patients clinically identified as having a tinnitus site of lesion primarily peripheral in location and cochlear in type. The present device is not commercially available at this time. Both specific and general suggestions are proposed for the standardization of methods of reporting results of electrical tinnitus suppression and tinnitus control. PMID- 3324770 TI - Gait changes in adult onset hemiplegia. AB - Multiple parameters of gait were evaluated in 50 adult acquired hemiplegic patients and 30 control patients with no history of gait abnormality and no deviation from normal gait by observational analysis. Findings in the hemiplegic group include: 1) increase in the proportion of the gait cycle spent in stance and double-limb support phases in both the normal and affected limb; 2) consistent deviation from normal gait pattern by observation and objective pattern analysis; 3) abnormal phasic activity of specific muscles and muscle groups in the affected limb; and 4) a consistent electrogoniometric deviation from normal joint ankle progression in the affected hip, knee and ankle. These data lend credence to the hypothesis that gait deviation in adult acquired hemiplegia follows a consistent pattern varying with the severity of central nervous system involvement. These data also provide a baseline from which to measure therapeutic intervention in this complex patient population. PMID- 3324771 TI - Poliomyelitis: late and unusual sequelae. AB - The purpose of this study is to provide a thorough and comprehensive description of the late onset manifestations of poliomyelitis (PM). In addition, unusual findings, seen in the post-poliomyelitis period, have been presented to further increase awareness of the potential diversity of the problem. The scope of PM sequelae is broad. Following a description of acute PM, the various sequelae are addressed categorically. These include neurologic, vascular, orthopedic, respiratory, sleep and psychologic problems; as well as less commonly recognized maladies. Different theories for PM sequelae have been proposed. Thorough electrodiagnostic testing can frequently confirm or negate the clinical impression. The pathophysiology of vascular problems, as well as the correlation between respiratory involvement, sleep disorders, and hypertension, is reviewed. Orthopedic problems and spinal deformities are discussed. Since overuse weakness is frequently present in these patients, the role of slowly progressive non fatiguing exercise in their rehabilitation is emphasized. Of significance are the emotional concerns demonstrated by this group of patients. Further considerations include those sequelae not readily recognized in relation to PM. A brief overview of present epidemiologic trends in the United States, and the immunologic effects of vaccination, is presented. PMID- 3324772 TI - Activity of motor units during concentric and eccentric contractions. AB - Motor unit activity was investigated in the biceps brachii of twelve men during concentric (CC) and eccentric (EC) contractions by means of computer aided intramuscular spike amplitude-frequency (ISAF) histograms and surface EMG frequency power spectral analyses. Simultaneous recordings of the intramuscular and surface EMG signals were made during both types of contractions with the elbow joint angle varying from 30 to 150 degrees in reference to a fully extended position. Results demonstrated that r.m.s. amplitude and mean power frequency of the surface EMG were significantly higher during CC, particularly at shorter muscle length; e.g., 259 vs. 131 microV (p less than 0.01) and 102 vs. 91 Hz (p less than 0.05). The intramuscular spike recordings made at 45, 90 and 135 degrees showed greater motor unit (MU) activities during CC along with the presence of MUs with relatively large spike amplitude. The pooled data on the ISAF histograms revealed significantly greater mean MU spike amplitude and frequency during CC as compared to EC; e.g., 439 vs. 108 microV and 16.1 vs. 13.0 Hz at 135 degrees, respectively. These data suggest that EC is associated with much less pronounced MU recruitment and rate modulation due to economical tension development which might be a result of better utilization of elastic energy, particularly those inherent in the actin-myosin cross bridges and also a favorable length-tension relationship under the present experimental conditions. PMID- 3324773 TI - Schizoid personality disorder: a synthesis of developmental, dynamic, and descriptive features. AB - Various views of schizoid personality disorder in descriptive psychiatry, psychoanalysis, DSM-III and DSM-III-R are reviewed and synthesized to develop a composite picture of the syndrome. The disorder is seen as consisting of characteristic deficits in six areas of psychosocial functioning: (1) self concept, (2) interpersonal relations, (3) social adaptation, (4) ethics, standards and ideals, (5) love and sexuality, and (6) cognitive style. Such a view maintains historical continuity in the use of the term "schizoid," combines descriptive and psychodynamic observations and correlates the behavioral and psychostructural aspects of the schizoid pathology. The paper also identifies guidelines for distinguishing the schizoid personality from other personality disorders as well as areas needing continued research. PMID- 3324774 TI - Testis lesions and cellular and humoral immune responses induced in rats by immunization with laminin. AB - Sixty-six percent of rats immunized with laminin isolated from a mouse Engelbreth Holm-Swarm (EHS) sarcoma developed moderate lesions in the testis characterized by multiple foci of seminiferous tubules with different degrees of sloughing of the germinal epithelium or atrophy intermingled with normal histological areas. Interstitial mononuclear cell infiltrates were seen in the epididymis. By electron microscopy, pathological changes in the basement membranes of the seminiferous tubules, such as splitting and focal thickenings of knob-like projections toward the epithelium, were observed. Moreover, Sertoli cell cytoplasm showed dilated smooth endoplasmic reticulum and large vacuoles. By electron microscopy with the immunoperoxidase technique, staining for in vivo bound rat IgG was detected along the walls of the seminiferous tubules as a bright linear immunofluorescence and as a dense reaction product on the basal lamina. High titers of circulating antilaminin antibodies were detected by ELISA in all the rats immunized with laminin. As revealed by the skin test, a delayed type hypersensitivity reaction to laminin was observed in these rats. PMID- 3324775 TI - The current status of antiplatelet antibodies. AB - The importance of antiplatelet antibodies in clinical medicine was first recognized in 1951. Since that time, a number of syndromes have been described, including autoimmune thrombocytopenia purpura, posttransfusion purpura, neonatal alloimmune thrombocytopenia, and drug-induced thrombocytopenia purpura, that fit into the category of immunologic thrombocytopenias. The laboratory methods for detecting the antiplatelet antibodies present in these diseases are enumerated and discussed along with the currently recognized platelet-specific antigens. Because of the complexities of performance and the lack of agreement among many of the available procedures, it is recommended that antiplatelet antibody testing remain primarily a research tool for the present time. PMID- 3324776 TI - Indirect mixed antiglobulin reaction (MAR) as a screening procedure for antisperm antibodies. II. Clinical studies. AB - In this study the question was raised whether the indirect mixed antiglobulin reaction (MAR) using donor spermatozoa could substitute the direct MAR requiring motile spermatozoa in the patient's ejaculate in the screening for antisperm antibodies. Serum and seminal plasma from 48 men selected on the basis of the results in the direct MAR were tested by the indirect MAR. Both tests were carried out for IgG and IgA antisperm antibodies. A statistically significant correlation was found both between the sperm-bound IgG and the free IgG antisperm antibodies in serum as well as in seminal plasma and between sperm-bound IgA and the free IgA antisperm antibodies in seminal plasma whereas no correlation was found between the sperm-bound IgA and the free IgA antisperm antibodies in serum. This finding strongly supports the concept that the major part of the IgA antisperm antibodies in the ejaculate are locally produced. PMID- 3324777 TI - How should sperm antibody tests be used clinically? AB - Immunoglobulin-specific assays are currently available for detection of patients with antibody-mediated infertility. Care must be taken in insuring that the correct immunoglobulin class is assayed, the assay is directed to the possible interaction of antibodies and sperm in the male or female genital tract, and the antigen employed will not detect antibodies against antigens not found on the plasma membrane of living sperm. PMID- 3324778 TI - Zona pellucida: current status as a candidate antigen for contraceptive vaccine development. AB - The porcine zona pellucida represents a unique immunocontraceptive target antigen. Initial active immunization studies using crude or partially purified zona components as immunogens resulted in adverse, nonreversible effects on ovarian folliculogenesis, but more recent findings in nonhuman primates indicate that such effects are not as severe and are reversible. Consequently, current efforts are directed toward identifying a zona immunogen that elicits contraceptive antibodies that produce no adverse effects on the ovary. Other studies are in progress to determine optimal injection/immunization format, proper immunogen dosage, and appropriate adjuvant for use in the zona-antizona immunocontraceptive system. Recent data have been very encouraging and emphasize the contraceptive efficacy of this approach to reproduction control. PMID- 3324779 TI - Genetic factors in fetal losses. AB - When all known causes of fetal losses are ruled out, there remains a small population of women (0.5-1.0%) who have recurrent fetal losses of unknown etiology. A significant proportion of these recurrent spontaneous abortions may be due to primarily genetic causes. The critical characteristic of couples experiencing such fetal losses is the sharing of HLA antigens between husband and wife. The hypothesis developed here states that the sharing of HLA antigens indicates the sharing of recessive lethal genes linked to the major histocompatibility antigens (MHC) and that the sharing of the antigens per se is not significant. These recessive lethal genes could act alone to cause fetal death, or they could act epistatically with lethal genes on other chromosomes. Several models of such genetic mechanisms and the observations from studies in experimental animals and from studies in humans to support these models are presented. PMID- 3324781 TI - Pathology of otosclerosis: a review. AB - Otosclerosis is a bone disorder of unknown etiology confined to the otic capsule. Failure of remodeling of newly formed vascular, woven bone (otospongiosis) results in sclerotic bone (otosclerosis) with abnormal osteons. Involvement of the oval window causes conductive hearing loss. Electron microscopic, histochemical, and biochemical studies identify normal cellular and matrix components of otosclerotic bone without providing clues to the abnormal bone formation and resorption. Plastic-embedded, nondecalcified histologic sections with in vivo tetracycline labels permit the study of mineralization rates to separate this disorder from other bone dyscrasias that have similar histopathologic appearances. Characterization of the cells, matrix, and their mediators can yield an understanding of abnormalities that disorder bone. PMID- 3324780 TI - New concepts in bone remodeling: an expanding role for the osteoblast. AB - Until recently, the prevailing view regarding the function of osteoblasts and osteoclasts was to attribute bone formation to the former and bone resorption to the latter. While the capacity of the osteoclast to degrade bone matrix remains unquestioned, there is now provocative evidence indicating that the osteoblast plays a critical role in regulating osteoclast resorptive activity as well as in contributing directly to matrix dissolution. The first of these points follows from observations indicating that the osteoblast (but not the osteoclast) 1) exhibits receptors and/or responses to resorption-promoting agents (including parathyroid hormone and vitamin D), and 2) releases agents capable of stimulating bone resorption. The second point is derived from studies demonstrating that the osteoblast produces neutral collagenase (an enzyme specialized to degrade type I collagen, the principal organic constituent of bone matrix) and an inhibitor capable of blocking collagenase activity. The synthesis of both of these proteins is, in part, regulated by parathyroid hormone and other resorption-stimulating agents and appears to involve control at the transcriptional, translational, and secretory levels. Thus, in both physiologic bone remodeling and modeling, as well as the altered bone turnover associated with some disease states, it is the osteoblast rather than the osteoclast that may hold the key to understanding the mechanism of tissue form and function. PMID- 3324782 TI - Otosclerosis and sensorineural hearing loss: a histopathologic study. AB - The precise role and mechanism whereby otosclerosis is associated with sensorineural hearing loss remains unclear. Previous histopathologic reports are inconsistent with regard to the location of the otosclerotic focus, invasion of the otic capsule, and the number of remaining peripheral sensorineural elements. From the combined temporal bone collections of the University of Chicago and the Mayo Clinic, we identified a group of 125 ears from 80 patients, all with confirmed otosclerosis. Six of these ears were associated clinically with sensorineural hearing loss without stapes fixation. The histopathology of the otosclerotic focus was reviewed in terms of its location and depth of invasion. The cochlea and spiral ganglion were reconstructed, and the state of the organ of Corti and the presence or absence of peripheral cochlear nerve fibers were noted. Correlations with ganglion cell counts were made. The present study showed that the pattern of degeneration of peripheral sensory and neural elements in the cases presented is very similar to that found in cases of age-related processes such as presbycusis. PMID- 3324783 TI - [Early echographic diagnosis of periventricular hemorrhage in premature infants]. PMID- 3324784 TI - [Artificial termination of pregnancy in late periods]. PMID- 3324785 TI - [Ultrasonic diagnosis of fetal congenital developmental anomalies]. PMID- 3324786 TI - [Our experience with ultrasonic diagnosis in threatened premature labor]. PMID- 3324787 TI - [The place and technic of vaginal hysterectomy in modern surgical gynecology]. PMID- 3324788 TI - [Our experience in treating women with vaginal candidal mycotic infection using a 0.25% riodoksol ointment]. PMID- 3324790 TI - [A method for the transvesical puncture of ovarian structures under ultrasonic control and local anesthesia]. PMID- 3324789 TI - [Basic lines in the prevention of acquired immunodeficiency syndrome (AIDS) morbidity using the means and potentials of maternal health care services]. PMID- 3324791 TI - [High-energy lasers in gynecological practice]. PMID- 3324792 TI - Neuropathological aspects of infantile spasms. AB - A review of the neuropathological findings in 50 personal autopsy cases and in the available literature (214 confirmed cases) of infantile spasms demonstrates that this type of early infantile epilepsy occurs in a wide range of cerebral lesions caused by various noxae during different stages of brain development. With regard to morphology and the presumed time of occurrence of the CNS lesions, four groups can be distinguished: (1) embryofetal lesions, including a) cerebral malformations or developmental disorders-agyria-pachygyria (lissencephaly), micrencephaly, micropolygyrias, (hemi)megalencephaly, agenesis of corpus callosum, tuberous sclerosis, heterotopias, cortical microdysplasias, b) metabolic disorders (leukodystrophies, neurolipidoses, spongy dystrophies, Leigh and Alpers diseases, aminoacidopathies); (2) perinatal and postnatal encephalopathies, e.g. polycystic brain, diffuse and lobar sclerosis, ulegyrias, white matter and basal ganglia scars, status marmoratus, hippocampal sclerosis, and cerebellar atrophy; (3) combined embryofetal (developmental) and perinatal or postnatal brain lesions, particularly association of microdysplasias with secondary anoxic or vascular changes; (4) acute vascular and inflammatory brain injuries; (5) cases without definite brain pathology. Evaluation of the available data indicates that embryo-fetal lesions alone or accompanied and/or superimposed by perinatal or postnatal lesions account for about 61% of the cases confirmed by autopsy, in which infantile spasms can be regarded as fetal epilepsies, while a smaller group is featured by perinatal or postnatal lesions occurring in early age, i.e. affecting the immature brain. Similar lesions are observed in cases showing transition of West syndrome to Lennox syndrome. Negative pathology findings in a small number of cases do not necessarily implicate negative pathobiology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324793 TI - Neuroradiological aspects of infantile spasms. AB - With the modern noninvasive brain imaging methods, cerebral lesions of different types and degrees can frequently be determined in infants with West syndrome. In CT examinations preceding the spasms and the ACTH therapy, "idiopathic" forms of infantile spasms were rare. The CT findings consistent with perinatal or postnatal encephalopathy were more frequent than those found with embryonic or fetal lesions alone. The fact that pathognomonic changes cannot be determined, may reflect the low specificity of CT diagnosis in infants with chronic CNS diseases. A slight and mostly transient enlargement of CSF spaces during ACTH therapy is a probable side-effect of the medication. In infants with persistent or progressive enlargement of the CSF spaces, however, this alteration appears to be mainly due to pre-existing brain damage. CT examinations of infants with West syndrome should be performed because prognostic information may be obtained and in a few cases operations to drain CSF may be necessary. PMID- 3324794 TI - Rett syndrome--a review and discussion of syndrome delineation and syndrome definition. AB - The current status of clinical genetic and pathogenetic knowledge in Rett syndrome is reviewed and updated. Some of the concepts which are highlighted include among others, casual homogeneity vs heterogeneity; the difficulty of dealing with potential variability while the possibility of heterogeneity still exists; progress in examining genetic hypotheses. We review our experience with 8 new patients, note the evidence for the presence of congenital hypotonia in all and several instances of minor anomalies and again raise the issue of whether girls with the Rett syndrome are in fact normal from the time of birth and in early infancy until the characteristic phenotype is recognizable. Previous recommendations for standardized international history, examination and investigation protocols are strongly reinforced, and the question as to who should study brains of Rett syndrome patients is raised by a parent. As is the case in most conditions now being studied by molecular geneticists, finding a marker will be a major etiologic breakthrough, but the work of delineating the pathogenesis will remain to be done. PMID- 3324795 TI - Rett syndrome: epidemiology and nosology--progress in knowledge 1986--a conference communication. AB - Recent progress from pooled clinical experience is reviewed. The approximate number of documented cases of Rett syndrome (RS) as of October 1986 was 1,100. Three sister pairs, 3 monozygotic twin pairs (both twin girls affected), 3 dizygotic twin pairs (one twin girl affected) are known. Genetics are discussed based on these and other known occurrences. Early seizure-onset variants have been reported in a dozen cases representing various countries. Approximately 20 incomplete RS related cases, also termed "formes frustes," are documented as of October 1986. An actual Swedish series of 66 classical RS, 4 "formes frustes," 2 early seizure-onset variants and 9 other clinically near related atypical cases is summarized. A suggested late stage IV spinal cord impairment is discussed, as well as the whole adult multifacetted complex neurological pattern. Gastrointestinal pathology is discussed with reference to possible generalized neuropeptide disturbances. PMID- 3324797 TI - Rett syndrome bibliography II, 1987. PMID- 3324796 TI - Practical and theoretical considerations concerning the genetics of the Rett syndrome. AB - The Rett syndrome is exclusively found in girls. Considerable interest has been focused on a possible genetic background. The evidence for such an etiology is not conclusive and the findings in support of such a hypothesis are given. The few twin data and family data together with the chromosomal investigation indicate an X-linked inheritance. The recurrence risk in a family with one Rett girl is about 0.3%. Prenatal diagnosis is not recommended for the time being, as the only diagnosis, possible is prenatal sexing and most girls are healthy as the recurrence risk is low. PMID- 3324798 TI - Acute alcohol intoxication: sex comparisons on pharmacokinetic and mood measures. AB - This study explored sex differences in pharmacokinetic and mood state responses to acute alcohol intoxication among socially drinking women demonstrated to be normally cycling across two consecutive menstrual cycles and men with similar drinking habits. Subjects were administered moderate or high alcohol doses in six experimental sessions over a 60-day period. Women were tested during the early follicular, ovulatory, and midluteal phases of the cycle, and men were administered alcohol at comparable time intervals. Results showed that men did not differ in alcohol pharmacokinetics across sessions, but women showed significantly shorter elimination times and faster disappearance rates during the midluteal phase of the menstrual cycle compared to the early follicular and ovulatory phases and to their male counterparts. There were no sex or within group differences in self-reported negative mood states prior to alcohol administration, but women described increased anxiety and depression while intoxicated during the early follicular compared to ovulatory and midluteal phases. Affective responses to intoxication were a complex function of sex, limb of the blood alcohol concentration-time curve, and dose. PMID- 3324799 TI - Alterations in brain aldehyde dehydrogenase activity modify ethanol-induced conditioned taste aversion. AB - The role of peripherally and centrally acting acetaldehyde in ethanol-induced conditioned taste aversion (CTA) was investigated using various enzyme manipulations. Cyanamide, an aldehyde dehydrogenase inhibitor (ALDH) elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole (4MP), an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide. Under both treatment conditions brain and liver ALDH activity is inhibited. Water-deprived rats were pretreated 4 hr prior to fluid presentation with intraperitoneal injections of saline (S+S), 4-methylpyrazole (4MP+S), cyanamide (S+C), or 4-methylpyrazole + cyanamide (4MP+C). Subsequently, animals were presented with a novel saccharin solution followed immediately by intraperitoneal injection of one of three doses of ethanol (0.4, 0.8, or 1.2 g/kg) or saline vehicle on four occasions. Results suggested that animals pretreated with cyanamide (groups S+C and 4MP+C) drank significantly less saccharin after conditioning with a subthreshold dose of ethanol (0.4 g/kg) in comparison to groups S+S and 4MP+S. Moreover, at the conditioning dose of 1.2 g/kg, cyanamide-treated animals demonstrated an attenuation of CTA compared to the other two groups. These effects cannot be attributed to elevated blood acetaldehyde levels since pretreatment with 4MP+C prevented peripheral acetaldehyde accumulation. A characteristic common to both cyanamide-treated groups was the inhibition of brain ALDH. It is therefore suggested that brain ALDH may play a role in the mediation of ethanol-induced CTAs. It is conceivable that ALDH plays this role by regulating the levels of acetaldehyde in brain. PMID- 3324800 TI - Naloxone, ethanol, and the chlorpropamide alcohol flush. AB - The effects of ethanol and subsequent administration of intravenous naloxone were studied in double-blind, placebo-controlled fashion with a group of six male chlorpropamide alcohol flushers (CPAF) and a group of 13 nonflushing males. The effect of ethanol intoxication on fine motor control was measured by a typing test. When sober, the two groups performed in comparable fashion. When intoxicated, the CPAF group displayed significantly greater impairment than the nonflushing group as measured by typing errors committed in 3 min (CPAF: 55.4 +/- 10.1 errors, n = 12; vs. nonflushing: 15.6 +/- 2.3, n = 32; p = 0.0000015 by Student's unpaired t test). Chlorpropamide alcohol flushers appeared to be more sensitive to ethanol. Naloxone reversed this effect for individuals in the CPAF group (saline treatment: 51.0 +/- 11.7 errors per minute; vs. naloxone treatment: 23.7 +/- 4.2; p = 0.034 by Student's paired t test, n = 6). Naloxone had no effect in the nonflushing group. Unlike the normal, nonflushing group, the CPAF group demonstrated an increased sensitivity to ethanol that was partially antagonized by naloxone. PMID- 3324802 TI - Human aldehyde dehydrogenase: metabolism of putrescine and histamine. AB - Imidazoleacetaldehyde and gamma-aminobutyraldehyde, metabolites of histamine and putrescine, respectively, have been shown to be substrates of human liver aldehyde dehydrogenase (EC 1.2.1.3) cytoplasmic (E1) and mitochondrial (E2) isozymes. The Km values at pH 7.4 and 500 microM NAD for imidazoleacetaldehyde and gamma-aminobutyraldehyde for the E1 isozyme are 40 and 800 microM, respectively, and for the E2 isozyme are 50 and 500 microM, respectively. The Km values with gamma-aminobutyraldehyde with both isozymes are high relative to Km values with acetaldehyde (50 microM for E1 and 1 microM for E2). Since activity with both imidazoleacetaldehyde and gamma-aminobutyraldehyde in crude liver homogenates paralleled that of aldehyde dehydrogenase (EC 1.2.1.3) during purification it appears likely that in the human liver this enzyme is responsible for metabolism of both compounds. If this is the case, interaction between metabolism of histamine and putrescine and that of alcohol is likely. Both imidazoleacetaldehyde and gamma-aminobutyraldehyde were synthesized in this laboratory and their stability has been investigated. Procedures for assaying aldehyde dehydrogenase employing synthetic metabolites of histamine and putrescine are provided. PMID- 3324801 TI - Urinary dolichol--a new marker of alcoholism. AB - Urinary dolichol levels of 31 skid-row alcoholics and 49 alcoholics entering a detoxification unit were compared to those of 51 nonalcoholic controls (social drinkers). The mean urinary dolichol content as related to urinary creatinine was significantly (p less than 0.001) higher in the two groups of alcoholics than in the controls. In this material the sensitivity of increased urinary dolichol in the detection of alcoholism was 68% as compared to 44% sensitivity of serum gamma glutamyltransferase. The percentage of false-positives in the control group was 3.9%. Urinary dolichol is suggested as a potential tool for the detection and follow-up of alcohol abuse. PMID- 3324803 TI - Effects of paternal alcohol consumption in mice. AB - Male mice were divided into four groups, one group was given ad libitum access to a liquid alcohol diet containing 35% ethanol derived calories (EDC). A second group was pair fed an isocaloric control diet containing 17.5% EDC whereas a third was similarly treated with a 0% EDC diet for a minimum of 42 days. A fourth group served as ad libitum nontreated controls to assess the role of pair feeding. Males were then mated with nontreated females. The males consuming alcohol had an increased percentage of abnormal sperm and there was a significant effect of paternal alcohol exposure on implantation sites, but no effect on pre- or postnatal mortality or fetal weight. These results suggest that paternal alcohol consumption adversely affects sperm production but does not affect development of offspring in mice. PMID- 3324804 TI - Morphometric parameters of Purkinje dendritic networks after ethanol treatment during aging. AB - Spine densities on terminal branches of Purkinje cell dendrites of Fischer 344 rats were significantly altered by ethanol treatment and aging processes. An effect of the control liquid diet on the lengths of terminal branches and an interaction effect of this diet with age on the numbers of terminal branches/cell also occurred, but there were no detectable interaction effects of ethanol with age on dendritic parameters. Changes in spine density on terminal branches, which accounted for 63-67% of the total dendritic length/cell, represented a major quantitative modulation of synaptic input to these neurons during age and following ethanol treatment. PMID- 3324806 TI - Quantification of individual sensitivities to ethanol in selective breeding experiments: difference scores versus regression residuals. AB - Nagoshi et al. (Alcohol Clin Exp Res 10:343-349, 1986) have argued recently that the use of postdrug minus predrug difference scores to assess individual variability in sensitivity or tolerance to ethanol is not to be recommended. Unreliability of variables can result in biased estimates of response to treatment. Instead of difference scores, they recommend using residual scores from the regression of posttreatment on pretreatment measures. We were interested in the consequences of employing difference scores versus regression residuals for a related, but different purpose: the choice of individual animals to be mated for a selective breeding study. The availability of data from such a selective breeding experiment ongoing in the laboratory of one of us (JCC) allowed us to compare directly the effects of use of change and residual scores as criteria for selection. The selection is for maximal hypothermic sensitivity of mice to an acute dose of ethanol. In our sample, difference scores were highly correlated with regression residuals. In practical terms, almost 75% of the individuals chosen for mating by the change score method would also have been chosen by the residual score method. We conclude that for selective breeding experiments, the use of difference scores does not necessarily introduce sampling bias, is unlikely to affect the ultimate outcome of selection, and may be a more meaningful variable for the physiological process studied. PMID- 3324805 TI - DSM-III criteria for alcohol abuse: associations with alcohol consumption behavior. AB - DSM-III criteria for diagnosing alcohol abuse in a sample of hospitalized alcoholics highly correlated with each other and were poorly correlated with self reported drinking pattern, quantity, and consequences of alcohol consumption. These findings question the specificity and the construct validity of the DSM-III criteria for diagnosing alcohol abuse. PMID- 3324807 TI - Cell cycle phase-specific perturbation of hepatic tumor cell growth kinetics during short-term in vitro exposure to ethanol. AB - Cell cycle events associated with the growth suppressive effects of short-term ethanol exposure on liver cells were investigated using flow cytometric methods to analyze the proliferative kinetics of ethanol-sensitive 32IIIA rat hepatic tumor cells. A 3-day exposure of exponentially growing 32IIIA cells to growth medium containing 100 mM ethyl alcohol decreased final population density (to less than 70% of control values) although viability was unaffected, approximating 94% under all experimental conditions. Comparative flow cytometric analysis of control and ethanol-treated populations revealed significant ethanol-associated alterations in the substate composition of G1 phase hepatic tumor cells. An ethanol-induced 30% increase in mean population doubling time was reflected in an approximately 22% increase in the proportion of G1 phase cells within a culture. Lower overall G1 cellular RNA content typified all ethanol-treated 32IIIA tumor cell populations. The fraction of G1 cells in the immediate pre-DNA-synthetic (G1B) compartment was markedly reduced (by 41-80%) during the period of ethanol exposure as were the percentages of S and G2+M phase cells which derive kinetically from cells in G1B. This reduction in the proportion of cells with normal G1B RNA levels was not reflected solely in the complement of very low RNA content "G1E-type" cells generated during the course of ethanol treatment. Net accumulations (of 19 and 34%) of cells residing in the G1A substate were consistent additional concomitants of ethanol treatment. Short-term ethanol exposure in the 32IIIA hepatic tumor cell system clearly impairs normal progression of such cells through the G1 phase of the cell division cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324808 TI - A preliminary study of hepatitis B virus replication during short-term (7-day) social drinking. AB - The purpose of this study is to determine the effect of short-term social drinking on hepatitis B virus (HBV) replication as measured by serum levels of hepatitis B virus DNA (HBV-DNA). We studied five male carriers of hepatitis B e antigen who were social drinkers. Levels of HBV-DNA, blood alcohol, and aspartate aminotransferase (AST) were measured during abstinence from alcohol, before and during a test dose (29.8 g) of alcohol which followed one week of abstinence, and before and during the same test dose which followed social drinking for one week. We observed no significant changes in HBV-DNA or AST levels. These data suggest that a single one-week period of social drinking in patients with chronic HBV infection does not cause enhanced viral replication. The risks of repeated ingestion of moderate amounts of alcohol by such patients have not been established. Interpretation of our data is limited by the small number of subjects, and further studies are needed. Nevertheless, our results are consistent with published recommendations that social drinking by nonalcoholic HBV carriers should be restricted but need not be totally forbidden. PMID- 3324809 TI - Effect of abstinence on the blood acetaldehyde response to a test dose of alcohol in alcoholics. AB - Following an acute dose of alcohol (0.15 g/kg intravenously), blood levels of acetaldehyde were significantly higher in nonabstinent alcoholics than in controls. After 2 weeks of abstinence, this blood acetaldehyde response significantly decreased in alcoholics and the acetaldehyde returned towards levels comparable to those observed in nonalcoholics. These results suggest that elevated blood acetaldehyde levels in the alcoholics are secondary to the chronic alcohol consumption rather than reflecting a primary preexisting defect. PMID- 3324811 TI - Relationship between acute ethanol-related responses in long-sleep and short sleep mice. AB - Long sleep (LS) and short sleep (SS) lines of mice were derived from a heterogeneous stock of mice (HS) and have been selectively bred on the basis of the time the animals were devoid of the righting reflex (sleep time) following acute ethanol administration. We have tested a large group of the HS mice for sleep time response to ethanol. Animals were then selected from the extremes of the HS sleep time response and designated short sleep (HS-SS) or long sleep (HS LS). The ED50 value for loss of righting reflex was compared between these mice (HS-SS and HS-LS) and animals that had undergone 25 generations of selection (SS and LS mice). The ED50 value was not significantly different for the HS-LS (1.9 g/kg) and LS (2.17 g/kg) mice but was markedly different between HS-SS (3.02 g/kg) and SS (4.21 g/kg) mice. The ED50 values for the eight inbred strains that constituted the HS stock ranged only from 2.33 to 2.78 g/kg. The value for LD50 one hour after ethanol administration was found to be 9.03 g/kg and for SS mice 6.94 g/kg for LS mice, in contrast to our previous findings of no difference in LD50 values between SS and LS mice when ascertained 24 hr after the ethanol dose. Since the two lines were selected only for a sleep time difference, a differential sensitivity to other consequences of acute ethanol exposure, such as the lethal dose, would not be expected unless the effects shared a common genetic mechanism of action with ethanol sleep time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324812 TI - [Infection in bronchial asthma]. PMID- 3324810 TI - Effects of aging and testosterone administration on liver alcohol dehydrogenase activity in male Fischer 344 rats. AB - The activity of alcohol dehydrogenase was measured in liver cytosolic fractions of male Fischer 344 rats at ages representing young adulthood, middle age, and old age. The activities were 1.7 +/- 0.1, 2.3 +/- 0.1, and 2.6 +/- 0.2 mumol/min/g liver in rats aged 4-5, 14-15, and 24-25 months, respectively. Hepatic alcohol dehydrogenase activity in female rats (3.4 +/- 0.2 mumol/min/g liver) was the same in young as in old rats. Castration increased alcohol dehydrogenase activity in young males to levels found in females, and testosterone administration reversed the effect. However, neither physiological nor pharmacological doses of the hormone restored the elevated enzyme activities of old male rats to levels found in young male rats. PMID- 3324813 TI - [Controversy in asthma. I. Staphylococcus aureus as the main factor responsible for bronchospasm]. PMID- 3324815 TI - The EEG and awareness during anaesthesia. PMID- 3324814 TI - [Controversy in asthma. II. A new vaccine prepared with the Cowan I strain of Staphylococcus aureus]. PMID- 3324816 TI - Hepatotoxicity and death following two enflurane anaesthetics. AB - A 67-year-old woman died with massive fatty change in the liver 41 hours after her second enflurane anaesthetic in 28 days. The clinical features of five previously reported similar deaths are summarised. Possible mechanisms of the hepatotoxicity are reviewed briefly. PMID- 3324817 TI - Comparison of the haemodynamic effects of intermittent positive pressure ventilation with high frequency jet ventilation. Studies following valvular heart surgery. AB - The cardiorespiratory effects of intermittent positive pressure ventilation and high frequency jet ventilation with and without positive end expiratory pressure were compared in patients following valvular heart surgery (mitral and/or aortic). Twenty patients received intermittent positive pressure ventilation and high frequency jet ventilation with 0, 0.5 and 1.0 kPa positive end expiratory pressure. High frequency jet ventilation was well tolerated. The addition of 1.0 kPa positive end expiratory pressure was associated with preservation of the arterial oxygen tension without any increase in shunt or significant adverse haemodynamic effect. The results are discussed and compared with a previous study of high frequency jet ventilation following aortocoronary bypass graft surgery. PMID- 3324818 TI - The use of opioids in neonates. A retrospective study of 933 cases. AB - This is a retrospective study on the use of postoperative opioids in neonates admitted to the surgical intensive care unit at Great Ormond Street over a 5-year period (1980-84). A total of 131 (14%) babies received opioids out of 933 neonates admitted to the unit. The use of opioids increased from 9.7% to 27.2% of admitted cases during the survey period. Postoperative ventilation of the lungs was necessary in 240 (25.7%) cases and 88 (36.6%) of these were given opioids. Four babies initially failed to wean from controlled ventilation as a result of opioid induced respiratory depression. A total of 51 (7.35%) spontaneously breathing neonates received opioids and seven (13.7%) of these developed apnoea or respiratory failure thought to be induced by opioids. The administration of opioids by nurses occurred most frequently in the late evening and early hours of the morning, when medical cover is at its lowest level. PMID- 3324819 TI - Molecular weight standards for calibration of gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis: ferritin and apoferritin. AB - Ferritin and apoferritin are widely used for the calibration of gel filtration columns and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and are commercially offered for these purposes as part of molecular weight calibration kits. Many of the reported applications are severely in error as presented in leading references and application manuals. The manufacturers have based their recommendations on incorrect physicochemical parameters in the literature and incorrect or inadmissible assumptions about the protein subunit composition and architecture and have not taken into account the unusual resistance of these proteins to denaturation in SDS. Here the relevant physicochemical parameters of horse spleen apoferritin as reported in the literature are critically reevaluated and the best current estimates are identified as the following: weight average molecular weight of apoferritin, Mw = 481,200; molecular weight of subunits, major subunit, ML = 19,889; minor subunit, MH = 22,200; apparent specific volumes in 0.02 M acetate buffer, pH 5.5, and 0.1 M NaCl, phi = 0.721 ml g-1 and phi' = 0.743 ml g-1; partial specific volume at 20 degrees C, v = 0.738 ml g-1; viscosimetric molar volume, M[n] = 1.78 X 10(6) ml mol-1; Stokes radius, RSt = 67.1 A; viscosimetric radius, Rvis = 65.6 A; sedimentation coefficient S degrees 20, w = 16.6 S; translational diffusion coefficient, D20, w = 3.24 X 10(-7) cm2 s-1. Recommendations are provided for proper application of ferritin and apoferritin for calibration purposes in gel filtration and SDS-polyacrylamide gel electrophoresis. PMID- 3324820 TI - One-step enzyme immunochromatographic assay for theophylline. AB - The convenience of the previously described enzyme immunochromatography method for visually quantifying theophylline in whole blood has been improved with the development of a one-step protocol. The capillary migration and color generation in the two-step enzyme immunochromatographic assay have been combined into a single step. Ascorbic acid is used as a signal inhibitor to delay enzymatic color product formation until the inhibitor itself is consumed. The concept of internal delay reaction is presented and the mechanism of ascorbate's action as an inhibitor to temporarily delay color generation is described. The internal delay reaction has been applied to a practical one-step quantitative visual enzyme immunochromatographic assay for theophylline in whole blood. PMID- 3324821 TI - Isolation of secretory vesicles from Saccharomyces cerevisiae. AB - Purification of secretory vesicles from Saccharomyces cerevisiae has been hindered because these organelles normally represent a small proportion of cellular membranes. In the yeast secretory mutant sec1, secretory vesicles accumulate intracellularly in large quantities. Using a sec1 strain we have devised a procedure for the partial purification of these vesicles. The purification employs differential and density gradient centrifugations and an electrophoretic separation of membranes. The fractions obtained from this procedure are enriched for secretory vesicles at least fivefold over other cellular membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized membrane fractions reveals a distinct set of polypeptides associated with secretory vesicles. PMID- 3324822 TI - Design, construction, and use of an electroporator for plant protoplasts and animal cells. AB - We have designed and constructed an electroporation device capable of efficient transfer of DNA into both plant cell protoplasts and cultured murine lymphocytes. The electroporator design allows various combinations of voltage and capacitance to be used to optimize the electric pulse. Switching of large voltages and currents is accomplished with a silicon-controlled rectifier, yielding excellent reproducibility and long component life. A safety switch is provided to permit complete discharge of the device. Conditions suitable for high levels of transient expression and high frequencies of stable transformation for both plant and animal cell systems have been found. PMID- 3324823 TI - The isolated perfused rat liver: preparation and application. PMID- 3324824 TI - Western blot detection of epidermal growth factor receptor from plasmalemma of culture cells using 125I-labeled epidermal growth factor. AB - We have developed a novel Western blot procedure for the detection of epidermal growth factor (EGF) receptors within a complex mixture of membrane proteins. Purified cell membranes from either human placenta or cultured A431 cells were solubilized, resolved by electrophoresis, and electroblotted onto nitrocellulose paper. With 5-15% gradient gels, electroblotting was completed in 2 h and both the high- and low-molecular-weight proteins were transferred evenly onto the nitrocellulose, as indicated by the radiolabeled protein markers. Upon hybridization with 125I-EGF, the membrane receptor was identified as two adjoining bands on the nitrocellulose of 150 and 170 kDa. Binding of 125I-EGF to the immobilized membrane receptor was specific and was displaced by excess unlabeled EGF. The receptor signal on the autoradiogram was optimized when 1% hemoglobin and 0.05% Tween 20 were present during the hybridization. The ligand binding activity of the immobilized receptor was not affected by sodium dodecyl sulfate detergent or ethylene glycol bis(beta-aminoethyl ether) N,N,N',N' tetraacetic acid, but was drastically reduced by either heat denaturation or the addition of dithiothreitol to the membrane samples. Using this method, we were able to demonstrate that no noticeable difference was observed between the pre- and postphosphorylated EGF receptors in their ability to bind to 125I-EGF. Because it allows both identification and purification of a receptor from a mixture of proteins, this protocol should have general application in characterizing various receptor-ligand systems. PMID- 3324825 TI - Stable isotope dilution assay for prostaglandin E metabolite: 24-hour urinary output in healthy male subjects. AB - A stable isotope dilution assay for the major urinary metabolite of prostaglandins E1 and E2 (PGE-M) was developed. After extraction and purification, the compound was converted to the dimethyl ester bis(O-methyloxime) trimethylsilyl ether derivative and quantified with the 13C-labeled dimethyl ester analog as internal standard. The interassay coefficient of variation was 0.8%, and the intraassay coefficient of variation ranged from 0.9 to 1.7%. The recovery of authentic, underivatized PGE-M added to urine was 99.5 +/- 3.2% (mean +/- SE, N = 9). The equation of the regression curve correlating the amounts added and recovered was Y = 1.05X - 5.84, with R = 0.998. The level of excreted metabolite in healthy male subjects was 13.86 +/- 1.46 micrograms/24 h (N = 24), in good agreement with data from other sources. PMID- 3324826 TI - Native blot and immunotransfer of human prostatic acid phosphatase isozymes. AB - Agarose gel isoelectrofocusing is used to separate the isozymes of human prostatic acid phosphatase with retention of enzyme activity. The native blotting of the isozymes onto a nitrocellulose membrane increases the sensitivity of the enzyme stain and is suitable for analysis of isozymes in prostate tissue, which contains little nonprostatic acid phosphatase. The specificity of the transfer is increased by treating the membrane with antibody to human prostatic acid phosphatase prior to the transfer. The specificity of the antibody is conferred to the membrane resulting in a transfer specific for prostatic acid phosphatase. The immunotransfer procedure is applicable to serum which contains appreciable amounts of nonprostatic acid phosphatase. PMID- 3324827 TI - Galvayne: the mystery surrounding the man and the eponym. PMID- 3324829 TI - Measurement of testosterone in seminal plasma, saliva and serum by solid-phase enzymeimmunoassay. AB - When testosterone concentrations in serum, saliva and seminal plasma were measured with a solid-phase enzymeimmunoassay in which antitestosterone antibody was bound to CNBr-Sepharose-4B, we found the ratios of testosterone in saliva and seminal plasma to that in serum were 2.5 +/- 0.2% and 5.19 +/- 0.42%. Testosterone level in saliva could be an index of free serum testosterone. In addition, we found a correlation between sperm motility and testosterone level in seminal plasma when sperm motility was measured with a transmembrane migration method. This enzymeimmunoassay could be applied to clinical studies of testosterone. PMID- 3324828 TI - Short-term effects of an LHRH-agonist alone or in combination with testosterone propionate or indomethacin on rat testes. Evidence of testosterone independent effects. I. AB - The treatment of adult male Wistar rats with a LHRH-agonist (lutrelin Wyeth/WY 40972) resulted in severe damage of the seminiferous tubules as well as in remarkable changes of the blood vessels within 24 hours. First striking signs of alterations within the blood vessels were already found 6 hours after the injection of lutrelin: the blood vessels were almost totally filled with leucocytes. Neither the effects on the germinal epithelium nor the effects on the blood vessels were prevented by the simultaneous treatment with 3 mg testosterone propionate (TP). The treatment with indomethacin, however, clearly antagonized both events. The complete inefficiency of TP to overcome the inhibitory effects of lutrelin on the testes does argue against an androgen deficiency as the primary cause. The results obtained with indomethacin strengthen the hypothesis, that the early deleterious effects of LHRH-agonists on the germinal epithelium of the rat are primarily caused by circulatory disturbances in the testes and that prostaglandins may act as mediators. PMID- 3324831 TI - [Pathophysiological aspects of endogenous intoxication in intestinal infection in children]. PMID- 3324830 TI - Vimentin expression in spermatogenic and Sertoli cells is stage-related in rat seminiferous epithelium. AB - Monoclonal and polyclonal antibodies were used in indirect immunofluorescence microscopy to localize vimentin intermediate filaments in the rat seminiferous epithelium. During stages XII-V of the epithelial cycle, the Sertoli cells showed a reaction in the perinuclear area and vimentin-positive extensions, projecting toward the developing spermatid bundles, were also seen. During stages VI-XI these extensions were small and narrow. Monoclonal antibody to vimentin gave a granular reaction in the peripheral region of the flagella of steps 16-19 spermatids. Western blotting indicated a specific reaction with a Mr 58,000 polypeptide in isolated seminiferous tubules and in epididymal spermatozoa. Our results suggest that vimentin filaments in Sertoli cells may be regulated cyclically in a stage-dependent manner. The granular reaction in the spermatid flagellum with the monoclonal antibody suggests that vimentin in germ cells is organized differently from that in somatic Sertoli cells. PMID- 3324832 TI - [The concept of re-inhalation and its history in anesthesiology]. PMID- 3324833 TI - [Function of anesthesia systems with different flow rates of fresh gas]. PMID- 3324834 TI - [Injection of halogens: an alternative to the use of vaporizers]. PMID- 3324835 TI - [Closed-circuit: description, heat and humidification]. PMID- 3324836 TI - [Respirators and reinhalation]. PMID- 3324837 TI - [Inhalation anesthetics and closed-circuits. Mathematical model and BASIC program]. PMID- 3324838 TI - [Midazolam used for premedication reinforces sleep induced by flunitrazepam]. AB - This single blind study aimed to discover possible effects of intramuscular premedication with midazolam on the sleep induced by intravenous flunitrazepam. 24 male patients, aged 17 to 71 years, who were to undergo surgery to the distal parts of an upper limb under regional anaesthesia, were randomly assigned to two equal groups: in the midazolam group, an intramuscular premedication of 0.12 mg.kg-1 midazolam with 0.5 mg atropine was given, whereas in the control group atropine only was used. In all patients, 1 mg flunitrazepam was given intravenously 45 min after the premedication, before carrying out regional anaesthesia. No other drug was given. In the midazolam group, the time of loss of spontaneous conversation was reduced (p less than 0.05), as well as the time of eye closure (p less than 0.001), and the time for recovery of the capacity to count backwards was increased (p less than 0.001). So, premedication with 0.12 mg.kg-1 midazolam intravenously 45 min before giving 1 mg flunitrazepam reinforced the sleep induced by the latter. PMID- 3324839 TI - Growth inhibition of Escherichia coli and Klebsiella pneumoniae during involution of the bovine mammary gland: relation to secretion composition. AB - Mammary secretions from 12 Holstein dairy cows were collected to evaluate growth inhibition of Escherichia coli and Klebsiella pneumoniae during involution and during physiologic transitions of the mammary gland. Mammary secretions obtained during late lactation poorly inhibited growth of E coli and K pneumoniae. However, as involution progressed, mammary secretions increasingly inhibited growth of both coliform mastitis pathogens. Greatest inhibition of E coli and K pneumoniae growth was observed when mammary glands were fully involuted. Growth inhibition remained high until 7 days before parturition, and then it decreased significantly (P less than 0.05) to that observed during late lactation. Inhibition of coliform mastitis pathogen growth was associated with high concentrations of lactoferrin and immunoglobulin G, decreased citrate concentration, and a low citrate to lactoferrin molar ratio. These data suggested that differences in susceptibility or resistance to new intramammary infection with coliform mastitis pathogens during the nonlactating period may be attributable, in part, to marked changes in mammary secretion composition that develop during physiologic transitions of the mammary gland. Resistance of the fully involuted mammary gland to coliform infection may be associated with high concentrations of natural protective factors. PMID- 3324840 TI - Fear, prejudice, and neglect. Discrimination against mentally disabled persons. PMID- 3324841 TI - The treatment utility of assessment. A functional approach to evaluating assessment quality. PMID- 3324842 TI - Protection of the patient in nuclear medicine. PMID- 3324843 TI - [What to expect from lymphocyte markers in 1987]. PMID- 3324844 TI - [Chest pains of esophageal origin. Is it possible to identify them and how?]. PMID- 3324845 TI - [Autoimmune neutropenia disclosing AIDS in a child]. AB - A 15 month old child with a history of multiple infectious diseases was admitted to hospital for investigation of pyrexia and general ill health. She was anaemic with a persistent neutropaenia associated with hypergamma globulinemia, indicating intense autoimmune activity: cellular immunity was abnormal with a normal total lymphocyte count but a very low T4/T8 ratio. HIV serology was positive; the virus was isolated from a lymph node biopsy specimen. The parents for the child were HIV positive and the father went on to develop full blown AIDS. The neutropaenia was constant over the two years of follow-up and granulo immunofluorescence studies suggested an autoimmune origin. In contrast to autoimmune thrombocytopaenia and haemolytic anaemia, autoimmune neutropaenia is a rare condition. A few cases have been reported in adult AIDS. Our case is of additional interest as it illustrates the vertical mode of transmission of AIDS. PMID- 3324847 TI - [Indications for the laser in gastroenterology]. PMID- 3324846 TI - [Lupus vasculitis]. AB - Anatomical studies have demonstrated the high incidence of vasculitis in SLE, the appearances of which are variable and non-specific, ranging from necrotizing angiitis which is undistinguishable from periarteritis nodosa, to scarring lesions. Micro-angiitis is easily demonstrated in skin lesions and is also encountered to varying degrees in CNS, renal, cardiac, pulmonary and gastrointestinal localisations. Disease of large vessels is more rare and sometimes causes gangrene of the limbs. In SLE, vasculitis should be distinguished from thrombosis related to lupus anticoagulant and from atherosclerosis favoured by chronic steroid therapy but perhaps initiated by vascular deposits of immune complexes during the acute inflammatory stage. The treatment of lupic angiitis is mainly based on steroid therapy. The results are variable, probably due to the fibrous nature of some of the vascular lesions. PMID- 3324848 TI - [Research methods in metabolic myopathies in children]. PMID- 3324849 TI - Redirection of cellular metabolism. Analysis and synthesis. PMID- 3324850 TI - Determining pathway structure-property relationships through experimentation and analytical frameworks. AB - A brief description of the information content of the experimental methods that are becoming increasingly useful for probing intracellular processes, a framework for interpreting observations, and an example that combines framework results and 13C NMR observations have been presented. Results in terms of structural criterion have been obtained that suggest that it may be possible to develop a glossary of structure-function heuristics. From the engineering point of view, such general work may also provide keys to system/subsystem modeling due to having some classic and nonclassic network properties mapped in advance. However, we note that approaches based solely on kinetics ignore physiochemical processes. A number of potential processes were mentioned earlier. Investigations of the importance of such processes, though, have been limited due to the dominance of in vitro enzyme kinetic and regulation work. Nonetheless, interesting proposals have been advanced by a limited number of workers, such as the suggestion that membrane-bound and soluble populations of enzymes with high and low activity, respectively, exist in eukaryotes (e.g., aldolase22) and the balanced attained between the two populations is an important regulatory mechanism. In an effort to contribute to the evaluation of physiochemical processes, our formalism was recently used to explore the logic of enzyme turnover number-enzyme amount distributions from the standpoint of minimizing excess enzymatic capacity (i.e., minimizing excess energy expenditure for protein biosynthesis) and the use of limited cytoplasmic solvation capacity (i.e., concentrated cytoplasm is water limited; hence, maintaining the solubility of all constituents is difficult). PMID- 3324851 TI - Large-scale culture of hybridoma and mammalian cells in fluidized bed bioreactors. PMID- 3324852 TI - Analysis of mammalian cell growth factor receptor dynamics. AB - We have proposed a mathematical model for the events following binding of EGF to cell surface receptors with the aim of elucidating possible mechanisms associated with a lack of responsiveness to EGF mitogenic stimulation. Comparison of our model calculations with the experiments of Schaudies et al. suggests at least two possible mechanisms: an increase in the rate of receptor synthesis, or an increase in the fraction of internalized receptors that are recycled to the cell surface. Discrimination between these alternatives requires experimental measurement of cell receptor quantities, such as the number of surface complexes or the amount of degraded receptor. At the present time, we speculate that an increase in the fraction of receptors recycled seems to be the more likely explanation. PMID- 3324853 TI - Maximizing productivity in an immobilized cell reactor. AB - A vertical immobilized cell reactor employing Saccharomyces cerevisiae cross linked to a gelatin support with glutaraldehyde has proven to be an effective system to achieve high cell concentrations and high dilution rates. The reactor is very stable over long periods of time, during which the cell concentration increases continuously without achieving steady state. Therefore, periodic regeneration by gas purging is required to remove excess biomass from the interstitial spaces. The glucose concentrations along the reactor follow an exponential profile when plotted as a function of the true residence time. Such profiles are a function of the initial glucose concentration fed to the system. The overall productivity of the reactor is a function of the flow rate and the inlet glucose concentration. For a 99% conversion, the maximum overall productivity is obtained at a substrate concentration of between 15% and 20%. Theoretical cell profiles were obtained and they indicate that mass transfer is promoted at high substrate concentrations and flow rates. The performance of a variety of packing materials having different shapes and materials of construction were compared in a vertical packed bed immobilized cell reactor. With other parameters being constant, the performance of the reactor is dominated by the quantity of cells present. The packing that has the highest surface area per volume of bed yields the most extensive monolayer and gives faster reactor start-up. Packing materials having high biomass loading rates are desirable at prolonged operating periods when growth beyond the monolayer occurs. Ultimately, the packing with the highest initial porosity would be capable of loading the highest cell volume, provided that sufficient interstitial spaces were provided for cell entrapment. When the immobilized cell reactor is operated in the horizontal position, CO2 holdup is decreased, as is evidenced by an increase in liquid holdup. However, the horizontal and vertical reactors showed almost identical substrate profiles at constant cell densities. In addition, under prolonged operation, the performance of the horizontal reactor decayed after several days, while the vertical reactor remained stable for over 40 days. The improved operation of this type of column in the vertical position is attributed to the necessary promotion of mass transfer with CO2 evolution and better liquid distribution. The addition of fatty acids to the media for an ICR results in limiting growth and increasing productivity. Overgrowth can be minimized, thus allowing longer periods of operation without regeneration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3324854 TI - A novel bioreactor system for biopolymer production. PMID- 3324856 TI - Role of motility, chemotaxis, and adhesion in microbial ecology. AB - This review emphasized the implications of recent data pertaining to the role that motility, chemotaxis, and adhesion play in microbial ecology. Some of these processes appear to promote colonization by allowing certain organisms to selectively "seek out" nutrients or sites of colonization. For example, chemotaxis to NO3- and NO2- may provide pseudomonads with such a strong competitive mechanism that it allows this group of bacteria to outcompete other members of the soil microbiota for these chemicals. Likewise, chemotaxis also allows other bacteria to enter and colonize the mucus gel lining the intestinal epithelium and thereby resist physical removal from the gut. On the other hand, the understanding of such mechanisms offers important new possibilities for the deliberate control of microorganisms for the benefit of man. To that end, much remains to be done before a thorough understanding of the ecology of the microflora of any ecosystem can be accomplished. It is hoped that this review will stimulate further work in this area, as well as to lead to collaboration between engineers and microbiologists, which should lead to fruitful and exciting research in the future. PMID- 3324855 TI - Protease production by immobilized Bacillus licheniformis. PMID- 3324857 TI - Microbial colonization of solid-liquid interfaces. PMID- 3324858 TI - Bacterial chemotaxis. Cell flux model, parameter measurement, population dynamics, and genetic manipulation. AB - In this paper, we summarized our recent efforts toward accomplishing four key goals important for control of microbial population dynamics in nonmixed systems: (1) derivation of a cell population flux model based on individual cell properties; (2) measurement of the population random motility and chemotaxis parameters appearing in this model using a simple experimental assay; (3) quantitative understanding of the effects of cell motility and chemotaxis properties on microbial population dynamics; and (4) manipulation of chemotactic responses by genetic modification. PMID- 3324859 TI - Some factors affecting the copy number of specific plasmids in Bacillus species. AB - Some factors affecting the copy number of specific plasmids in different hosts were presented. A low copy number (one copy per chromosome) Kmr Tcr plasmid pTB19 was isolated from thermophilic bacillus. We have constructed 22 derivatives from pTB19 and their copy numbers range from 1 to 214 per chromosome in B. subtilis and B. stearothermophilus. Some recombinant plasmids containing the specific 1.0 MDa EcoRI fragment exhibited high transformation frequency and low copy number in B. stearothermophilus and were stable in the thermophile; on the other hand, those plasmids were unstable in different host B. subtilis, as mentioned earlier. By selecting the best combination of vector plasmid and host strain, both molecular cloning of various enzyme genes (i.e., penicillinase, thermostable alpha-amylase, and thermostable neutral protease) and enhancement of the enzyme production could be easily achieved. PMID- 3324860 TI - Intelligent sensors in biotechnology. Applications for the monitoring of fermentations and cellular metabolism. PMID- 3324861 TI - Control of bacterial fermentations. PMID- 3324862 TI - Bioreactor operating strategies for microbial lipids from carbohydrates. PMID- 3324863 TI - Process development of a prototype extractive fermentation system. PMID- 3324864 TI - Enzymatic synthesis of L-ascorbic acid via D-uronic acids; membrane-reactor integrated recovery of D-galacturonic acid from pectin hydrolysates. PMID- 3324865 TI - Enhanced oxygen transfer using oil-in-water dispersions. PMID- 3324867 TI - Thermalizer. High-temperature short-time sterilization of heat-sensitive biological materials. PMID- 3324866 TI - Scaleup strategies for bioreactors containing non-Newtonian broths. PMID- 3324868 TI - The influence of PEG on alpha-amylase production with Bacillus species. PMID- 3324869 TI - A distributed model of enzymatic lysis of microbial cells. PMID- 3324870 TI - Construction of a vector plasmid that can be maintained stably at higher temperatures in Bacillus stearothermophilus and its application. PMID- 3324871 TI - Jute fiber as a filter medium in microbial air filters. PMID- 3324872 TI - The behavior of immobilized living cells. Characterization using isotopic tracers. PMID- 3324873 TI - Evolutionary patterns in sensory receptors. An exercise in ultrastructural paleontology. PMID- 3324874 TI - Adaptation processes in insect olfactory receptors. Mechanisms and behavioral significance. AB - Adaptation was studied in single olfactory receptor cells of male moths of Bombyx mori and Antheraea polyphemus. Receptor potential and nerve impulse generators have different and very likely, spatially separate adaptation mechanisms possibly located in the outer dendritic segment and the cell soma, respectively. Restricted portions of the receptor cell dendrite can be locally adapted. The impulse generator may exhibit at least two distinct adaptation processes with different kinetics, as deduced from a consideration of the phasic-tonic response and the different adaptation properties of each of these phases. The response characteristics of cells in the same sensillum are different. The "faster" responding cell types resolve odor pulses with frequencies up to 10 per second--a performance that is probably needed for orientation during flight toward a small odor source. PMID- 3324875 TI - Neural derivation of sound source location in the barn owl. An example of a computational map. PMID- 3324876 TI - Organization of olfactory bulb output cells and their local circuits. PMID- 3324877 TI - Cortical organization in gustatory perception. PMID- 3324878 TI - Effects of odorant mixtures on olfactory receptor cells. AB - The general mechanisms by which chemical stimuli may influence the firing frequency of olfactory neurons were briefly described. They include specific mechanisms mediated by receptor molecules and nonspecific mechanisms involving general properties of the chemicals and of cells. It is difficult to imagine that odorant mixtures influence receptor cells by mechanisms that are fundamentally different from those by which homogeneous chemicals act. It is argued that even under the best experimental conditions the presentation of odorants usually or always involves exposing the receptor cells to more than one additional molecular species compared to the unstimulated condition. This is because odorants invariably have contaminants that may be of potency such that their contribution to the odor is large even though their contribution to the number of molecules in the stimulus stream is small. Furthermore, the partition coefficients of the major and minor components are unlikely to be identical; therefore, their relative concentrations in the aqueous environment of the receptor cells can differ greatly from that in the gas phase. Finally, metabolic transformations of odorants in the olfactory mucosa can result in the exposure of receptor cells to mixtures of odorant and metabolites, with the mixture composition varying with time. Finally, some pitfalls in analyzing the effects of odorant mixtures are discussed. At the very least, it is necessary to determine the relation of concentration to response for each odorant in the mixture in order to interpret results in terms of interactions. Even with such data caution must be used, especially in attaching significance to reductions in the apparent maximal responses to one odorant induced by the presence of the other. PMID- 3324879 TI - Coding of chemosensory stimulus mixtures. AB - It appears likely that substantial processing of odor mixtures is done by peripheral olfactory structures. Both physiological and psychophysical data suggest that the first step is differential adsorption of constituents by the olfactory mucus, which separates and concentrates constituents in epithelial regions where neurons are most responsive to them. The second step involves the diffusion of adsorbed odorants through the mucus and activation of the receptor neurons. In contrast to the minute times involved in the first step, the time taken to diffuse through the layer and stimulate neurons is large, varies markedly between odorants, and is concentration dependent. The second step, therefore, provides another process for separating the actions of individual odorants. Both processes either separately or combined can account for mixture phenomena such as suppression and masking. Defining the role of each process with different mixtures of odorants that have different molecular properties is clearly a goal for future studies. PMID- 3324880 TI - Psychophysical models for mixtures of tastants and mixtures of odorants. PMID- 3324881 TI - Electrophysiological responses of olfactory receptor neurons to stimulation with mixtures of individual pheromone components. AB - Multicomponent pheromone systems are the rule in many species. As our knowledge about the number and kinds of different chemical compounds actually employed in the communication system of a particular species has increased, so too has our appreciation for the level of neurobiological complexity that must underlie these capabilities. The supposition that mixtures are differentially processed in the nervous system arises most easily when biologically relevant materials are evaluated, either singly or in multicomponent blends, with modern behavioral assay techniques. It is becoming increasingly clear that this increase in the chemical and behavioral complexity of a particular communication system must be paralleled by an increase in the efficiency of the physiological mechanisms employed for the neural encoding of behaviorally relevant odor compounds and blends. Here we review several studies that have examined the electrical activity elicited in primary olfactory receptor neurons when they are stimulated with mixtures of odorants. Particular attention is given to the responses elicited in a subset of the individual pheromone-sensitive sensilla on the antennae of male cabbage looper moths (Trichoplusia ni). Electrophysiological responses to single- and multiple-component stimuli, each drawn from among the seven known behaviorally active compounds for this insect, were obtained at several different stimulus intensities. Both (Z)7-dodecenyl acetate and (Z)7-dodecenol were effective stimuli for both of the receptor neurons found in one of the two classes of pheromone-sensitive sensilla, even at relatively low stimulus intensities (0.0005 micrograms). Dodecyl acetate, although behaviorally active, did not significantly excite either of these receptor neurons. However, when mixed with either of the unsaturated components, it significantly enhanced the receptor neuron's response to its appropriate parent compound only in the middle range of stimulus intensities. A mixture of all three components did not show this enhancement and at the middle range of intensities actually elicited reduced responses when compared to those elicited by appropriate amounts of any of the one- and two-component stimuli evaluated. Thus, some blends elicited electrical responses from primary olfactory receptor neurons that were not readily predicted from a knowledge of the receptor neurons' response to individual components. PMID- 3324882 TI - Odor-taste mixtures. AB - A solution with both an odor and a taste may be considered to be a mixture that involves two sensory modalities. Estimates of the intensity of such mixtures appear to be additive. If the overall intensity of each of the unmixed components is compared with the overall intensity of the mixture, the additivity approaches 100%. If the intensities of the smell and taste of the unmixed components are compared with the overall intensity of the mixture, the additivity is less than 100%. Thus, the specific question that is given to the subjects influences the magnitude of the estimations. This suggests that the additive process involves a central (cognitive) mechanism. Considering that the perception of complex flavors also involves sensory information of touch, temperature, and possibly vision and hearing, a central interpretation seems appropriate. The influences of smell on the perception of taste also appear to involve a cognitive mechanism. These smell taste confusions appear to be stimulus specific and are usually resolved in favor of taste. This may be true because the sensations of pressure, movement, and resistance are usually localized in the mouth. These accompanying sensations then suggest that the taste organs are active in determining the result even when no true taste is present. The influences of taste on the perception of smell are most pronounced when the tastant contains an odor. This suggests that the effect may be peripheral. That is, odorant molecules may be moving from the pharynx, through the posterior nares, to the olfactory receptors. If this interpretation is correct, the influences of taste on smell may be an odor-odor mixture involving "retronasal" and "nasal" olfaction. PMID- 3324883 TI - Sensory transduction in flagellate bacteria. AB - Flagellate bacteria can respond to a wide range of environmental chemicals and a variety of physical parameters, and integrate those responses. The most important thing for a cell is to maintain its energy level; bacteria therefore respond directly to any changes in their PMF. This has been likened to higher organisms responding to a physiological change, for example, a fall in blood glucose. In addition, if the PMF is high, the cell is free to respond to a limited range of metabolites and possibly move to an area that will allow an increased growth rate. Bacteria do not sense all amino acids, as the space available on the cytoplasmic membrane is limited, and a change in a few important metabolites is probably a good measure of the general environment around the cell. The sensory response does not require either transport into the cell or metabolism of the chemical, only the binding to the specific MCP. The cell could have a mutation in the pathway metabolizing the chemoeffector, but it would still respond to changes in the concentration of that compound. This taken with the ability of the cells to adapt to the stimulus has been considered to be the prokaryotic equivalent of smell and taste. PMID- 3324884 TI - A molecular vocabulary for olfaction. AB - Olfactory research is entering a new phase, in which molecular mechanisms are being revealed that go considerably beyond traditional concepts. New ways of characterizing these mechanisms are needed, and some suggestions toward that goal have been made in this review. These suggestions recognize that, whereas formerly our terms and concepts regarding olfactory stimulus-response characteristics came mainly from organic chemists and psychophysicists, the main impetus at present comes from molecular biology. A desirable terminology, therefore, is one that is familiar to molecular biologists and can facilitate comparisons with other systems--immune, endocrine, nervous--where similar methods and terms are in use. The suggestions made here for the olfactory system could also be adapted for the taste system. Taste stimulation could be characterized, for example, in terms of gustagens interacting with G-cell receptors, stimulation being determined by the gustatope of a particular ion or molecule. It should be emphasized that such terms and mechanisms may not need to be invoked in studies at behavioral or psychophysical levels. However, the need for them at the receptor level may well be an accurate reflection of our progress in applying methods of molecular biology to these systems. PMID- 3324886 TI - [Dental reimplantation and transplantation]. AB - Purpose of the inquiry about dental replantation and transplantation and about principal operating methods is to explain to the practice dentist these technics as an extreme help when he is compelled to save a tooth. A logical utilisation of these therapeutic processes will allow, preserving some dental elements esteemed "lost", to postpone as much as possible in time the prosthesis construction and to maintain physiologically look and function of dental arches. PMID- 3324887 TI - [Role of the obstetrician and the health institution in active involvement of the family nucleus during pregnancy, delivery and puerperium (preliminary note)]. PMID- 3324885 TI - [Insulin-dependent diabetes and pregnancy. A model of coordinated approach]. AB - A historical account of the relation between diabetes and pregnancy is followed by the presentation of a personal series of 10 insulin-dependent diabetic pregnant women (3 White's class B, 2 class C, 3 class D and 2 class F/R) treated in accordance with a newly applied quarterly and fortnightly protocol. Nearly normal blood sugar (HbA1 maintained around 8% in the second and third trimester) was achieved through home blood glucose self-monitoring, in keeping with the Karen Bruni Centre's educational programme. This includes self-management of intensified insulin treatment in the form of 2-3 injections per day (Monotard MC and HM, Actrapid MC and HM), as well as the use of Novo Pen (100 U/ml Actrapid HM) for supplementary insulinisation. Average insulin initial dose: 0.51 U/Kg/day (range 0.2-0.7); final dose 0.83 U/Kg/day (range 0.6-1.2). Delivery was by caesarean section on obstetric indication: 9 at the 36th week, 1 at the 34th for trisymptomatic gestosis. There were no foetal nor neonatal death. All children were subjected to intensive neonatological care. There were 3 cases of macrosomia and 1 tetralogy of Fallot, which followed a benign course. Despite their absence of statistical value, these data show that optimised multidisciplinary treatment can be of utility in preventing neonatal morbidity and mortality in an insulin dependent diabetic pregnancy. They also indicate that a coordinated treatment model can equally be put into effect even in a non centralised structure, provided certain facilities exist: in our case, voluntary support on the part of Karen Bruni Diabetic Association, obstetric interest in diabetology and a neonatological background for treatment of the offspring of diabetic mothers. Lastly, this series substantiate the effectiveness of the programme of self checking and self-management of diabetes in the accomplishment of "optimised" blood glucose control and containment of costly hospitalisation at the time of delivery. PMID- 3324888 TI - [Chronology of dental calcification and eruption in humans]. PMID- 3324890 TI - [Santa Maria dei Faxana Hospital of Vercelli]. PMID- 3324889 TI - [S. Bridget of the Scots Hospital and the Pozzo di Vercelli Boarding School]. PMID- 3324891 TI - [Evolution of the omnivorous dentition]. AB - Authors deal with the evolution of the omnivorous dentition, specially concerning the "changes" determined in men by different functions. PMID- 3324893 TI - [Metastatic Darier-Ferrand dermatofibrosarcoma. Review of the literature apropos of a case]. AB - We report the case of a 56-year old male patient with pulmonary, abdominal and pelvic metastases from a dermatofibrosarcoma (DFS) which had developed 23 years previously in the right scapulo-humeral region and had recurred twice after the first excision, in 1983. Surgery was only performed once. The most remarkable feature of the disease was the progressive transformation, with each recurrence, of a typical DFS into a poorly differentiated and highly malignant tumour, about as active as a fibrosarcoma. A review of the literature yielded 31 cases of histologically proven metastatic DFS. Although the actual incidence of metastases is difficult to determine with accuracy, their frequency may be estimated at 3 p. 100 (most probably a maximum figure). The disease spreads mostly through the blood, but also sometimes through the blood and lymph. However, since lymphatic involvement is rare the usefulness of lymph node excision is extremely doubtful. Pulmonary lesions are the most frequent ones, but various other organs may be affected, although this seldom applies to the liver. Following a first excision, metastases occur within 6 years on average (range: 1 to 33 years). This mean delay is superior to the mean follow-up period for most of the important series without metastases. The histopathological picture is usually one of typical DFS but in some cases, including ours, it is much less typical and may even be frankly malignant. A few reports mention the presence of histiocytic infiltrates associated with the fibroblasts. The prognosis in patients with metastases is particularly poor: in most of the cases reported the patient died within the year following the discovery of metastatic lesions. The very high progressivity of the secondary lesions contrasts with the slow course of the primary tumour. None of the treatments tried (surgery, radiotherapy, chemotherapy) has resulted in a significant prolongation of life. No correlation can be established between the occurrence of metastases and the following parameters taken together: patient's age and sex, tim elapsed between the appearance of the tumour and the date of exicision, and histological features of the initial tumour. The development and number of recurrences seems to be the most significant predictive factor as regards the risk of metastasis. The noxious role of incomplete and/or repeated surgery creating vascular breaks, disrupting the defense barriers and encouraging malignancy in some cases has been mentioned by most authors; it emphasizes the value of the widest possible initial surgery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3324892 TI - [Physiological aspects of deglutition]. AB - Mechanisms of deglutition physiology and fundamental characteristics that allow swallowing to accomplish its absolutely necessary vital function are shortly analysed. PMID- 3324894 TI - [Pemphigus induced by captopril]. PMID- 3324895 TI - [A case for a diagnosis: infantile acropustulosis]. PMID- 3324896 TI - [Congenital dyschromia]. PMID- 3324897 TI - [The problem of a lymphocytic infiltration of the skin of non-specific appearance]. PMID- 3324898 TI - [Skin surface lipids in man: origin, synthesis and regulation]. PMID- 3324899 TI - [Acral lentiginous melanoma]. PMID- 3324900 TI - [Polymorphonuclear eosinophils]. PMID- 3324901 TI - [Current treatment of genital condylomas]. PMID- 3324903 TI - [Management of cardiac murmurs in the newborn infant]. PMID- 3324902 TI - [Erysipelas]. PMID- 3324904 TI - [Management of severe kidney failure in neonates and infants]. PMID- 3324905 TI - [Current status of the detection and treatment of dislocation of the hip in infants]. PMID- 3324906 TI - [Biliary reconstruction by choledocho-jejunal anastomosis with a Y-loop in hepatic transplantation. Analysis of complications]. PMID- 3324907 TI - [Treatment of cystic formations of chronic pancreatitis. Apropos of 41 cases]. PMID- 3324908 TI - [Splenic autotransplantation in splenic injuries]. PMID- 3324909 TI - [Skin expansion in reconstructive surgery]. PMID- 3324910 TI - [Prognostic value of the exercise test after myocardial infarction]. AB - A stress test performed in the early stage after myocardial infarction enables to evaluate directly or indirectly three of the main prognosis factors: alteration of ventricular function, presence of ventricular arrhythmias, residual ischemia. This test, performed around the 15th day, after previous anti-angina treatment have been discontinued, is only done in the absence of the classic contra indications. It permits to detect abnormalities: electrical positivity (with or without pain), disorder of the ventricular rhythm, abnormality of the blood pressure profile, low stress level. The predictive value of these abnormalities has been the subject of many studies. Although all the results are not in agreement, each one of these abnormalities seems to carry an increased risk of cardiac occurrences after myocardial infarction. In addition, an early stress test enables to detect pluritroncular coronary lesions with, however, an average sensitivity. Thallium scintigraphy in conjunction with a stress test improves, however, the performances of this test. The advantage of an early stress test is the rapid screening of high risk patients who should benefit from additional exploratory measures and possibly of myocardial revascularization procedures. PMID- 3324911 TI - [Non-invasive methods of evaluation in hypertensive patients]. AB - Major strides have been made, in the past few years, in the field of arterial hypertension, due to the availability of methods permitting a non-invasive, and precise evaluation, outside of the office, of the blood pressure as well as the cardiac response to chronic pressure surcharge. The devices used to record pressure profiles, in an ambulatory situation, are periodically activated, either automatically or by the patient himself. They are portable blood pressure recorders connected to a conventional inflatable arm cuff. The arterial blood pressure thus measured may be quite different from that measured by a physician. The value of the arterial blood pressure recorded in ambulatory is not predictable on the basis of the values obtained in a medical environment. An important factor is that the risk of cardiovascular complication seems to be better correlated to the blood pressure measurements obtained in the usual patient's environment than to those taken by the physician. Sonocardiography is another non-invasive method allowing a better screening of the patients likely to benefit from an antihypertensive treatment. A left ventricular hypertrophy may be detected quite early in an hypertensive patient. The regression of such anomaly under antihypertensive treatment permits to ascertain the good quality of the blood pressure control obtained with antihypertensive medications. PMID- 3324912 TI - [Myocardial toxicity of free radicals of oxygen during the ischemia revascularization sequence. A re-assertion]. AB - There is at this point a large number of experimental studies suggesting that oxygen free radicals play a major role in the pathogenesis of the myocardial lesions observed during the sequence ischemia-revascularization. Today, it is stressed upon the role of leucocytes as well as iron as major mediators in triggering and maintaining free radicals generating reactions which lead to a lipidic peroxidation of the membranes. It is probable, and anyway desirable, that these converging studies result, in the very near future, in the development of free radicals traps which are clinically usable. Such a development is still undissociable from the identification of specific markers of radicals lesions in the tissues, which is a mandatory condition for a serious evaluation of the procedures likely to bring under control the harmful effects of these unstable oxygen derivatives and therefore complete the arsenal of anti-ischemic treatments. PMID- 3324913 TI - [Cardiac transplantation. Selection of patients and long-term results]. AB - Performed for the first time in the world, in December 1967, by Barnard in Capetown, and for the first time in Europe by our team in April 1968, cardiac transplantation has now 20 years of clinical applications. A best selection of the recipients, a more precise selection of donors, refinements in surgical technique, a better and earlier diagnosis of post-operative complications, more effective therapeutic means especially cyclosporin, have brought us, from 1981, such major improvements that many teams were prompted to resume the procedure. In our experience of more than 400 transplants at La Pitie Hospital, a five-year follow-up shows that 70 p. cent of the patients are alive, having resumed a normal familial, social, professional and often sporting life. Much progress remains to be achieved, but this procedure now seems to be quite common if not routine, only limited by the insufficient number of donors. PMID- 3324914 TI - [Carotido-vertebral study with ultrasonics]. AB - Sonotomography, associated with the Doppler test, permits an atraumatic exploration of quite a satisfactory precision of the carotid and vertebral arteries in their cervical portion. This type of exploration was used in patients with parietal lesions of these vessels, arterio-venous malformations or a cerebral arterial spasm. In these lesions of the wall and lumen of the arteries, the problem is to reconsider the place of this examination as compared to arteriography with injection of contrast material, from the diagnostic as well as pre-therapeutic standpoint. PMID- 3324915 TI - [Acute myocardial infarction. Different treatment, different prognosis?]. AB - Many statistics demonstrate a definite improvement of myocardial infarction during hospitalization, especially a decrease in the mortality. It appears tempting to credit that improvement to the numerous modifications of the treatment of this dangerous disease in the last few decades. The study reported here indicates, however, that other factors must be taken into account. We compared the evolution of two groups of patients hospitalized for acute myocardial infection, 10 years apart: The first group (G1) of 731 patients corresponds to years 1970-1975; the second group (G2) of 729 patients, corresponds to the years 1984-85-86. During these ten years, mortality decreased by 38 p. cent, from 19.2 p. cent (G1) to 11.9 p. cent (G2). This decrease remains significant regardless of age and sex, except in two subgroups with the least number of patients, i.e. women under the age of 65 and men over 65. It should be noted that rhythm disorders occur with the same frequency in both sub-groups while atrio-ventricular blocks seem to have decreased. The difference in the mortality cannot be attributed to the patient's selection. In fact, in both groups, they are comparable regarding the men/women ratio, the age distribution and the presence of main risk factors (tobacco abuse, dyslipidemia, arterial hypertension, diabetes, heredity). The treatment results in many alterations especially concerning diuretics which seem to be used in approximately 30 p. cent of the patients in both groups. On the contrary, steroids, prescribed in 25.3 p. cent of G1 patients are abandoned; electro-systolic stimulation established in 21.2 p. cent of G1 patients, concerned only 4 p. cent of G2 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324916 TI - Innominate artery rupture. A fatal complication of tracheostomy. AB - Tracheo-innominate artery fistula is an uncommon but frequently fatal complication of tracheostomy. The case histories of three patients with tracheo innominate artery fistula are presented, and one is a longterm survivor. The haemorrhage can be controlled by hyperinflation of the cuff of the tracheostomy tube or by direct digital compression of the artery. The damaged segment of the eroded artery should be resected and the ends oversewn. Measures to prevent this complication are described. PMID- 3324917 TI - The effect of washing with chlorhexidine soap on wound infection rate in general surgery. A controlled clinical study. AB - Postoperative wound infections in clean surgery were studied to compare the effect of preoperative whole body disinfection with chlorhexidine soap with that of local washing and no washing at all, respectively. The study includes 1530 operations for biliary tract disease, inguinal hernia and breast cancer. The overall infection rate was 3.4%. Among patient who had a preoperative shower with Chlorhexidine the wound infection rate was significantly reduced. PMID- 3324919 TI - Muscle pedicled bone graft in revascularization of aseptic necrosis of the humeral head. AB - A deltoid muscle-pedicled bone graft was used to treat avascular necrosis of the humeral head. Eighteen months later there was evidence of clinical improvement of the joint function, and plain x-rays and tomography showed signs of graft fusion in the recipient bed with reorganization of the formerly necrotic bone matrix in the humeral head. PMID- 3324918 TI - Treatment of delayed union and non-union of the carpal scaphoid with a compression staple and cancellous bone grafting--new method and preliminary results. AB - Scaphoid non-union (eight cases) and delayed union (three cases) were treated by compression staple and inlay of cancellous bone from iliac crest between the bony fragments. Union was achieved in ten of the cases (91 per cent). The consolidation time was 8-12 weeks in seven cases and 24 weeks or more in three cases. The compression stable fixation connected with bone grafting is a new and simple method to treat chronic fractures of the carpal scaphoid which is a difficult problem. The early results appear promising. PMID- 3324920 TI - Colonoscopic polypectomy as a tool for management of colonic polyps and detection of new lesions. AB - Over the past 14 years 1,000 polyps were removed via colonscope and histologically examined. There were 869 neoplastic polyps including 125 carcinomas. Non-neoplastic polyps included 32 inflammatory polyps, 32 metaplastic polyps, 27 juvenile polyps and 17 Peutz-Jeghers type polyps. Ninety-eight focal carcinomas were adequately treated by polypectomy only, whereas 9 out of 26 invasive carcinoma required further operations with one residual carcinoma in the pararectal tissue and colonic wall respectively. The criteria requiring additional surgery in invasive carcinoma are 1) lymphatic permeation of the submucosa, 2) poorly differentiated carcinoma or 3) massive invasion close to the cut end. Not only polypoid adenomas but also flat adenomas were found to exist and seem to play an important role in the adenoma-carcinoma sequence. It became clear that colonscopic polypectomy was a useful tool for the management of colonic polyps. PMID- 3324921 TI - Biochemical modulation of fluorouracil therapy in advanced colorectal cancer. AB - Fluorouracil has been the mainstay of chemotherapy in colorectal cancer for many years. We report our experience using fluorouracil in combination with other drugs which may modulate the spectrum of activity. Patients have been treated with allopurinol and fluorouracil and with two schedules of methotrexate and fluorouracil. We discuss other possible approaches to modulate fluorouracil action. PMID- 3324922 TI - Ischaemic colitis in systemic lupus erythematosus--report of a case and review of the literature. AB - We report a case of perforation of the colon from systemic lupus erythematosus (SLE) presenting initially with diarrhoea and later with acute abdominal symptoms. She was found to have widespread arteriolitis involving the colon resulting in necrosis, ulceration and perforation with peritonitis and ultimately, death from septicaemia. Although intra-abdominal symptoms are not uncommon in cases of SLE, actual involvement of the gastrointestinal tract of a degree severe enough to warrant surgical intervention is a relatively uncommon phenomenon. PMID- 3324923 TI - Diverticular disease of the colon in Japan. AB - In order to clarify characteristics of diverticular disease in Japan, 625 patients with diverticular disease were studied. The frequency was 13.3% and increasing with years. The right-sided type was seen in 68.8% and was common in the younger patients. 77 patients were complicated with diverticulitis; 61 presented right sided diverticulitis and 16 left-sided diverticulitis. Most of those with right-sided diverticulitis recovered with medical treatment successfully. Drainage and supplemental appendectomy were recommended procedure for emergency operation. Patients with recurring inflammation should receive elective right hemicolectomy. Intraluminal pressure studies disclosed abnormal motility with high intraluminal pressure of the ascending colon in the patients with right-sided diverticular disease. This abnormal motility might play an important role in the pathogenesis of right-sided diverticular disease. PMID- 3324924 TI - [Hormonal control of the differentiation of hypothalamic neurons in cell culture]. AB - Hypothalamic cell cultures represent a suitable model for studying the role of hormones during the development of the hypothalamus. In vitro studies have shown that oestradiol increases the neurite length in some hypothalamic nuclei and the number of LH-RH neurons. Triiodothyronine had no effect on the number of neurons but controlled the size and the neurite length of hypothalamic dopaminergic neurons. In contrast, mesencephalic DA neurons are regulated differently by T3. The effects of hormones in culture are correlated with the presence of specific nuclear binding sites. At last, serum-free cultures have demonstrated the importance of the interaction between hormones (T3, corticosterone) and others diffusible factors (polyunsaturated fatty acids) on the potassium evoked release of thyroliberin and on the maturation of synapses. PMID- 3324925 TI - [Interactions between the central nervous system, the endocrine pancreas and metabolism]. AB - 1. The importance of nervous circuits including neural afferences, their integration by the central nervous system and the resulting efferents is illustrated by comparing glucose tolerance following the spontaneous ingestion or the intragastric administration of a glucose load. When these circuits are by passed (intragastric glucose administration), glucose tolerance is impaired and accompanied by an increased insulin output compared to the situation of normal glucose ingestion. This is due to a decreased glucose utilization in the absence of the numerous reflexes that are elicited by the presence of glucose in the oropharynx. 2. In normal animals, insulin secretion by the B cell of the endocrine pancreas is under an inhibitory tonus by the sympathetic nervous system while the parasympathetic system has no stimulatory tonus. After acute bilateral destruction of the ventromedial hypothalamic nuclei (VMH), such a situation is reversed and there is an activation of the parasympathetic outflow leading to hyperinsulinemia. This hyperinsulinemia is partly responsible for the development of the obesity of VMH-lesioned animals and is accompanied by a decreased activity of some sympathetic efferents amongst which those innervating brown adipose tissue. Analogous data have been obtained when studying genetically obese fa/fa rats. 3. A peptide of around 1'000 daltons extracted from the rat hypothalamus and having insulin secretion promoting activity could possibly be an insulin releasing factor since it is present not only in the hypothalamus but also in the plasma. PMID- 3324926 TI - [Perfusion of the hypothalamus in vitro and release of neurohormones]. AB - A review is presented on the historical, practical and physiological aspects in the use of in vitro superfusion of the hypothalamus as a dynamic approach for studying the regulation of neurohormonal release. Advantages and possibilities brought about by the method are presented: sensibility, reproducibility and dynamic study of the pattern of neurohormone release, without a possible retroactive action of released substances on the perifused tissue. PMID- 3324927 TI - [Hepatitis due to nonsteroidal anti-inflammatory agents]. AB - The extended prescription of non-steroidal anti-inflammatory drugs in medical practice involve numerous adverse effects. Among them, hepatic injuries, rather uncommon, are very diverse with regard to clinical type and evolution scheme, according to the derivatives used. Salicylates, when taken at high doses, increase serum transaminases, mostly without overt clinical symptoms. Phenylbutazone is obviously hepatotoxic: it induces cytolytic hepatitis, in some cases with fatal issue. Among the indole derivatives, indometacine was involved, especially in children; mixed hepatitis have been noted during sulindac therapy, mostly with favourable outcome. In the group of propionic acid derivatives, ibuprofen, pirprofen and naproxen have been implicated in hepatitis of various types; ibufenac and benoxaprofen were quickly retired after occasioning several deaths. Concerning others non-steroidal anti-inflammatory drugs, some cases have been reported with piroxicam and diclofenac. Hepatotoxicity mechanisms are often unknown; they appear different according to each drug. Besides, the rheumatic disease under treatment and pharmacokinetic particularities (sulindac, diclofenac) might be important in this view. Monitoring of serum hepatic-enzyme concentrations seems recommended for patients receiving non-steroidal anti inflammatory for long time therapy. PMID- 3324928 TI - [Pancreatic enzymes with pH-dependent liberation]. PMID- 3324929 TI - [Digestive surgery: which lasers for which surgery?]. PMID- 3324930 TI - The population of a Wiltshire village in the nineteenth century: a reconstitution study of Berwick St James, 1841-71. AB - This paper reports an exploratory reconstruction of the village of Berwick St James in Wiltshire using nominative information from nineteenth-century English censuses and ecclesiastical registers of baptisms, marriages and burials between 1841 and 1871. The data are first described, and a procedure for sorting and linking records from different censuses, and for linking census records to registration records, is outlined. A detailed analysis of population turnover in the village reveals that after 1851 there was a period of heavy net out migration. Those who left the parish were overwhelmingly young people, and females were more likely to move out than males: almost all the females born in the parish between 1841 and 1851 had moved away by 1871. A consequence of this pattern of out-migration was that by 1871 there was a shortage of females in the marriageable age-groups (15-29 years). It is clear that this method of reconstructing English village populations promises new insights into the demography of rural England in the nineteenth-century, including, in addition to population turnover and migration patterns, such aspects as fertility levels and trends. A number of problems with the technique remain, however, notably our ignorance of the typical length of the period between birth and baptism. PMID- 3324931 TI - Males, females and hermaphrodites. An inaugural lecture delivered by Professor Ursula Mittwoch at University College London on 24 October 1985. AB - Ancient myths of an hermaphrodite origin of man and his subsequent bisection into male and female individuals receive unexpected confirmation from the embryological evidence. The genital ridge contains the components to form either a testis or an ovary, while two sets of genital ducts are the forerunners of the male and female reproductive tracts. The presence of potentially hermaphrodite rudiments in different organisms resulted in the failure of attempts to formulate the determination of sex in terms of classical genetics. This, in turn, has led to the hypothesis that the function of the mammalian Y chromosome is to enhance the growth of the gonadal rudiment in male embryos. The hypothesis provides an explanation for the observed bilateral asymmetry of gonadal differentiation in human hermaphrodites in terms of the bilateral asymmetry of growth of human fetal gonads. The human condition can be related to the marked asymmetry of gonadal growth and differentiation in birds. The effect of temperature in the determination of sex in alligators has likewise been explained in terms of gonadal growth. The variety of sex-determining mechanisms met with in vertebrates suggests a non-sex-specific effect adapted to specific biological needs. It is suggested that certain DNA sequences on the human Y chromosome act by enhancing the growth of somatic cells in the gonadal rudiment, leading to precocious differentiation of the testis. PMID- 3324932 TI - Fibroblasts against cancer cells in vitro. AB - In coculture experiments of HeLa cells with normal human fibroblasts, the parameters cell:cell ratio and feeding frequency can be monitored in a way that the growth of fibroblasts can flourish to the point where fibroblasts attack and destroy cancer cells. PMID- 3324933 TI - Physiological aspects of membrane lipid fluidity in malignancy. AB - Membrane lipid bilayer fluidity has a crucial role in signal transduction for a variety of biologically active molecules which activate cellular functions, cell differentiation and proliferation. No general trend is discernible in tumors regarding the direction of alteration in membrane fluidity. In hepatomas, the membrane fluidity decreases, whereas in neural tumors, lymphomas and leukemias, the membrane fluidity seems increased. The capability of cancer cells to metastasize seems to be related to the degree of membrane lipid fluidity. The possibility that cancer cell plasma membrane contains cryptic antidromic antigens becoming exposed by altering the fluidity, has triggered a potentially new approach in the treatment of neoplastic diseases. Further exploration into the mechanisms by which biologically active substances alter the membrane fluidity, may provide clues for understanding the mechanism of tumor growth and cancer metastases. PMID- 3324934 TI - Perspectives for the chemotherapy of AIDS. AB - In the design of selective inhibitors of the human immunodeficiency virus (HIV), the etiologic agent of AIDS, various steps of the virus replicative cycle could be envisaged as targets, i.e. virus adsorption to its cellular receptor (or another early event in virus replication such as penetration or uncoating), transcription of the viral RNA genome to proviral DNA (reverse transcription), trans-activation of viral mRNA transcription and translation, and, finally, virus release ("budding", or another late event in virus replication such as the assembly process). Although some potent HIV inhibitors such as heparin and dextran sulfate may interfere with an early step of the virus replicative cycle (adsorption) and others (interferon and interferon inducers) are assumed to act at a late step (budding), the majority of the anti-HIV agents appear to act at the reverse transcriptase level. Most of these reverse transcriptase inhibitors belong to the class of the 2',3'-dideoxynucleosides (ddN), and within this class of compounds a variety of 2',3'-dideoxy-, 2',3'-didehydro-2',3'-dideoxy-, 3' azido-2',3'-dideoxy- and 3'-fluoro-2',3'-dideoxyribosides of both purines and pyrimidines have been described as potent and selective anti-HIV agents. Akin to 3'-azido-2',3'-dideoxythymidine (AZT), the sole anti-HIV compound that has so far been licensed for clinical use in the treatment of AIDS, all other ddN analogues are postulated to interact as competitive inhibitors (with respect to the natural substrates) and/or chain terminators of the HIV reverse transcriptase. To do so, the ddN analogues need first to be phosphorylated by cellular kinases to the corresponding 5'-triphosphates (ddNTPs), and together with the affinity of the ddNTPs for the HIV reverse transcriptase (relative to their affinity for the cellular DNA polymerases), the extent by which the ddNs are phosphorylated to the ddNTPs are critical determinants of their potency and selectivity as anti-HIV agents. Much more remains to be learned about the in vivo efficacy of the 2',3' dideoxynucleoside analogues, and their pharmacokinetic and toxicological properties, before their true potential in the treatment of AIDS can be fully assessed. PMID- 3324935 TI - Sex-hormone-binding globulin and breast cancer risk. AB - We have measured serum concentrations of SHBG in 5000 women over the age of 35. In both premenopausal and postmenopausal women who were not suffering from cancer or other diseases or taking drugs likely to affect SHBG, the protein decreased with increasing weight and was lower in single nulliparous women than in married nulliparous women or parous women. In premenopausal women, SHBG was higher in women with late menarche. These findings suggest that diminished SHBG concentrations may be associated with the increased risk for breast cancer conferred by nulliparity and early menarche. PMID- 3324936 TI - Evaluation of models for steroid-protein interactions in malignancy. AB - Over the past two decades many model systems have been proposed for the steroid protein interaction in target cells. The most widely used two-step model in malignant tissue is now seriously questioned. With the advent of advancing methodology and monoclonal antibodies the new models support nuclear localisation of the receptor, the clinical significance of this in cancer treatment is far from clear. These latter models are not without drawbacks themselves. Immunological, and immunocytochemical techniques in particular, cannot provide full binding parameters on receptor status, its affinity for a steroid, the number and nature of binding sites. Thus the ligand binding assay still remains useful and in combination with immunological techniques should provide information that neither technique can provide alone. This approach has great promise in the evaluation of receptor status in cancer. The interactions of steroids with intracellular non-steroid proteins and receptor-independent phenomena are indicative of the complexities that the designers of models will have to contend with. PMID- 3324937 TI - Cancers-associated with HIV infection. AB - The spectrum of neoplastic disease seen in patients with the acquired immune deficiency syndrome (AIDS) is similar to that seen in several congenital and iatrogenic immunodeficiency states and provides a human model for studying neoplastic transformation in the immune compromised host. High grade lymphoid neoplasia, particularly of the central nervous system (CNS), as well as a virulent form of Kaposi's sarcoma (KS) and several types of squamous cell carcinomas, are appearing at an alarming rate in patients with AIDS. There is substantial serologic, pathologic and molecular evidence linking cytomegalovirus (CMV) to KS and Epstein-Barr virus (EBV) to squamous cell carcinoma and high grade B-cell non-Hodgkin's lymphoma (NHL). The human T-cell lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV) may be responsible for the permissive immune deficient state allowing for opportunistic neoplasia and the aggressive biologic behavior and atypical anatomic distribution these neoplasms exhibit. The clinical features as well as potential etiopathogenetic mechanisms of these malignancies are reviewed. PMID- 3324938 TI - Use of mutagenicity assays in studies of human cancer. AB - Analysis of human body fluids and excreta for mutagenic activity is used for monitoring occupational exposure to mutagens and carcinogens and for investigating the aetiology of human cancer, especially tumours of the gastro intestinal tract. The assays most commonly used for these studies employ reverse mutation from amino-acid auxotrophy to prototrophy in bacteria. The critical features of such tests are reviewed, together with the major variables which may confound the interpretation of data collected from such studies. The most important confounding variables are use of tobacco, diet and intake of medicines and drugs. The advantages and disadvantages of body-fluid analysis are summarised and a comprehensive bibliography is provided. PMID- 3324939 TI - Meta-analysis of cancer trials: a new approach to the assessment of treatment. AB - Meta-analysis of clinical trials offers the opportunity to pool results from a number of randomised studies so increasing the statistical ability to detect the value of treatment. More accurate estimates of the likely size of such effects can also be obtained. Subset analysis, which is seldom reliable in individual clinical trials, can be made more trustworthy. Meta-analysis of randomised trials of adjuvant therapy in early breast cancer illustrates the value of such analyses. These have helped not only routine clinical practice but also thrown light upon biological mechanisms and directed future research. Meta-analyses or overviews are playing an increasingly prominent role in cancer research. They offer the opportunity to maximise the use of information about a given treatment by combining the results from multiple randomised trials in a meaningful way. Whilst data from studies examining the same issue cannot simply be combined (due to trial heterogeneity), summation of the treatment effect across trials can be performed. It is reasonably assumed that differences between studies are differences in magnitude rather than differences in direction. The net result of such a process is to produce a result which is more accurate in its estimate of treatment benefit than its component parts. PMID- 3324940 TI - Metastases of human tumors in experimental animals. AB - A large variety of models of both artificial and spontaneous metastases have been developed in experimental animals. These models have enabled the characterization of metastatic cancer cells and have helped in understanding the metastatic process. Studies of experimental metastases of human tumors have so far been rather limited; these have been developed by xenografting human tumors in immuno compromised animals, especially athymic nude mice. Although nude mice only seldom develop metastases when grafted with human tumor cells, the selection of human cancer cells with increased metastatic abilities could be obtained in a number of cases. Human melanoma variants and clones with increased metastatic abilities were obtained from melanoma cell lines in nude mice and in immunosuppressed newborn rats. Subcutaneous transplantation in a nude mouse of a human melanoma metastatic nodule resulted in a subcutaneous tumor (NTT) and in spontaneous lung (NTP) and lymph node (NTG) metastases which were first maintained in vivo by subcutaneous passages in nude mice and then cultured in vitro as cell lines. Cytogenetic studies showed that all three tumor lines have a common origin and that metastases resulted from a population selection. After 15 in vitro passages, NTP cells were reinjected s.c. in nude mice: serial transplantation was accompanied by an increase in metastatic abilities of tumor cells. Melanoma cell lines, tumorigenic but non metastatic in nude mice were xenografted to ATS treated newborn rats. 3 weeks after s.c. injection of 10(6) cells, nearly all rats developed tumors and a proportion of them lung and lymph node metastases. Agar cloning of M4Beu line showed that it is heterogeneous and contains poorly tumorigenic but highly metastatic cells. In addition, serial in vivo passages resulted in the selection of highly tumorigenic but poorly metastatic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324941 TI - Purification and biochemical properties of Pitton's type 2 beta-lactamase (SHV 1). AB - A five-step procedure has been developed for purifying Pitton's type 2 plasmid mediated beta-lactamase (PIT-2, also called SHV-1) from cultures of a hyperproducing variant of an Escherichia coli K12 strain carrying the plasmid p453. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed a single protein band with a molecular weight of about 27,500. The amino acid composition of the protein and the amino acid sequence of the NH2-terminal region have been determined. PIT-2 enzyme contains 272 amino acid residues with 2 cysteines. Studies of the S-carboxymethylated protein (previously reduced or unreduced) suggest that these two residues are presumably in the form of free sulphydryl groups in the native protein. Conversely, TEM-2 beta-lactamase contains 2 cysteine residues which are in the form of a disulphide bond. Comparison of PIT-2 with other beta-lactamases was made using the difference index (DI) of Metzger et al. The PIT-2 enzyme appeared more closely related to the TEM-type penicillinases (DI of 6.5). PMID- 3324942 TI - Klebsiella pneumoniae C3 lipopolysaccharide mutants obtained by resistance to bacteriophage FC3-9. AB - Bacteriophage FC3-9 is one of the several bacteriophages of Klebsiella pneumoniae C3 isolated in our laboratory. Mutants resistant to this bacteriophage were isolated and found to be devoid of lipopolysaccharide O antigen, modified in outer-membrane protein composition and sensitive to complement killing (serum sensitive), unlike the wild-type strain. Serum-resistant mutants were isolated from these strains. They regained the lipopolysaccharide O antigen and the wild type outer membrane protein composition and became sensitive to bacteriophage FC3 9. PMID- 3324943 TI - Virulence-associated plasmids of Salmonella serotype Typhimurium in experimental murine infection. AB - The growth pattern of Salmonella enterica subsp. enterica serotype Typhimurium (Typhimurium) was studied in mice to examine the role of the 60-Mdal virulence associated plasmid in the pathogenesis of mouse typhoid. After repeated subcultures at 45 degrees C, isogenic variants harbouring the virulence associated plasmid (strains C52, TM122 and TM332) or having lost this large plasmid (strains C53, TM123 and TM333) were obtained from three parental strains (strains C5, TM12 and TM33, respectively). Plasmid pIP1350, present in strain C52, was tagged by Tn10 and transferred by successive conjugations to strains C53, TM123 and TM333. The behaviour of these three Typhimurium lines was studied in C57BL/6, DBA2, B6D2 (C57BL/6 X DBA2 F1 hybrid) and OF1 mice after oral infection, subcutaneous injection into the hind footpad or intravenous inoculation. The kinetics of organ colonization were followed at intervals after injection by enumeration of viable bacteria in caecum, mesenteric or popliteal lymph node, spleen, liver, kidney and lung depending on the route of infection. Strains harbouring virulence plasmid and their cured derivatives did not differ significantly in their ability to colonize caecal content and to translocate to draining lymph nodes. Elimination of the virulence plasmid was correlated with a significant reduction in the ability of cured variants to colonize spleen and liver. Reintroduction of the virulence plasmid into plasmidless variants restored the virulence to the level originally observed. These data demonstrate that a 60 Mdal plasmid in Typhimurium strains is necessary to ensure colonization of spleen and liver of experimentally infected mice. PMID- 3324945 TI - [The anatomy of erection]. AB - The authors review the current knowledge concerning the anatomy of erection. The nervi erigentes pass through the hypogastric plexus, travel along the cavernous nerve and terminate in the smooth muscle of the erectile bodies. There appears to be three types of nerves: adrenergic nerves, cholinergic nerves and non adrenergic, noncholinergic nerves. The arterial blood supply is derived from branches of the internal pudendal artery. The venous drainage occurs via the circumflex veins towards the deep dorsal vein of the penis. The corpus cavernosum is composed of a thick, extensible albuginea which contains an extensible vascular network surrounded by smooth muscle tissue, which, when it contracts, appears to induce detumescence and, when it relaxes, appears to allow inflow of blood into the erectile bodies. PMID- 3324944 TI - [Epidemiologic significance of the immunofluorescence typing of Chlamydia psittaci]. AB - A group of 39 strains isolated from pigeons, parakeets, parrots, sheep, goats, cats, guinea-pigs, mice and humans were immunotyped by a one-way or two-way cross reaction micro-immunofluorescence test. Eight immunotypes were found. Among them, two new immunotypes were characterized: a cat conjunctivitis strain and a mouse inapparent respiratory infection strain. The immunotypes of feline pneumonitis and guinea-pig conjunctivitis, recently described by Perez-Martinez and Storz, were confirmed. Three human strains were similar to avian isolates, while a fourth was identical to that of feline pneumonitis; this suggests a possible contamination of humans by cats. PMID- 3324946 TI - [Preventive antibiotic treatment in urology. Transactions of a round table at the 80th Congress of the French Society of Urology 1986]. PMID- 3324947 TI - Primary progressive aphasia--differentiation from Alzheimer's disease. PMID- 3324948 TI - On-off phenomenon: relation to levodopa pharmacokinetics and pharmacodynamics. AB - Motor function in the moderately to severely affected parkinsonian patient is critically dependent upon delivery of levodopa to the striatum. This, in turn, is influenced by the fluctuating plasma concentrations of levodopa produced by the drug's short half-life and erratic absorption, and by modifiable transport at the blood-brain barrier. Duration of response to a single dose of levodopa is proportional to peak plasma drug levels, and paradoxical responses may occur when plasma concentrations are in the vicinity of minimum effective concentrations. Thus the strategy of administering frequent, small doses of levodopa may contribute additional unpredictability to a fluctuating clinical response imposed by pharmacokinetic factors. PMID- 3324949 TI - Does papaverine interact with levodopa in Parkinson's disease? PMID- 3324950 TI - Clonidine in Gilles de la Tourette's syndrome. PMID- 3324951 TI - [A means of refining the sterilization criterion]. AB - The process efficiency parameter used in estimation of thermal sterilization of nutrient media known as a sterilization criterion is replaced by a new one. A methodical approach to and the results of experimental determination of corrections for the sterilization criterion pattern connected with the operation factors are presented. The following parameters for measuring the criterion were elucidated: contamination of nutrient media, retention time and kinetic characteristics of test-microbe death. Sterilization conditions were calculated with the routine procedure and the new method. Comparison of the results showed that the retention time calculated with the account of the corrections was much closer to the experimental values for the time of the test-microbe death. PMID- 3324952 TI - [Chemotherapeutic effectiveness of mecillinam and dioxidine in an experiment using polyresistant Escherichia coli]. AB - Chemotherapeutic efficacy of mecillinam and dioxidine was studied on a model of Escherichia coli septicemia of albino mice caused by polyresistant variants of E. coli 675. It was shown that the presence of RI plasmid in the bacterial cells markedly lowered the mecillinam chemotherapeutic efficacy whereas the presence of R64 plasmid did not change the drug efficacy as compared to the plasmid-free controls. It was noted that the presence of RI and R222 plasmids in the pathogen cells increased the dioxidine efficacy while pKM-101 plasmid had a contrary effect. Correlation between the level of dioxidine resistance of E. coli 675 in vitro and the drug chemotherapeutic efficacy in animals was observed. PMID- 3324953 TI - [Dependence of the antimicrobial effect on the antibiotic concentration in modelling pharmacokinetic profiles in vitro: a comparison of 2 regimens for the single intravenous administration of sisomicin]. AB - Kinetics of sisomicin antimicrobial effect on E. coli was studied in an in vitro dynamic model. Pharmacokinetic profiles observed in blood of humans treated with different polar dosing schedules i. e. bolus administration and continuous infusion were simulated. The first set of the experiments included simulating the profiles observed at short-term maintenance (0.25-20 min) of relatively high antibiotic levels after bolus administration (Cmax = 0.125-10 micrograms/ml). The second set included simulating the profiles observed at long-term maintenance (1 15 hours) of relatively low antibiotic levels after infusion (Cmax = 0.125-1.75 micrograms/ml). Changes in the viable count in the dynamic model were estimated microcolorimetrically with BioActivity Monitor LKB 2277-202. The use of the recently developed parameters of antimicrobial effect intensity IE and duration TE provided determination of relationship between IE or TE and logarithm of the area under the concentration-time curve (lg AUC). Its own IE (or TE) vs lg AUC curve including 4 phases corresponded to every administration schedule i. e. bolus and infusion. The 1st and 3rd phases reflected weak changes in IE or TE at significant increasing of the AUC and the 2nd and 4th phases reflected a marked increase in IE or TE at insignificant changing of the AUC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324954 TI - [Structure and biological activity of low-molecular interferon inducers]. PMID- 3324956 TI - Prospective randomized controlled study of ciprofloxacin versus imipenem cilastatin in severe clinical infections. AB - In a randomized prospective study, 66 patients with serious bacterial infections- mainly lower respiratory tract infections--were treated with either imipenem plus cilastatin (32 patients) or ciprofloxacin (34 patients); 30 patients in each group were evaluable for efficacy. Substantial underlying disease was present in most of the patients; pathogens isolated prior to treatment (77 isolates) consisted mainly of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and streptococci. Of the etiologic bacteria, 67% were eradicated by ciprofloxacin treatment and 79% by imipenem therapy; however, two patients (6.7%) failed in the ciprofloxacin group, and six patients (20%) did not respond to imipenem treatment (P = 0.25). All patients with therapeutic failures suffered from severe fatal underlying diseases, which had substantial impact on the outcome of treatment. Therapeutic drug monitoring in the ciprofloxacin patients revealed higher concentrations in serum at days 4 and 8 in comparison with day 1 of treatment, indicating that steady-state conditions were reached between days 1 and 4. The total number of side effects was relatively high--eight imipenem patients (25%) and six ciprofloxacin patients (18%) had reactions. Treatment had to be discontinued due to adverse reactions for three ciprofloxacin patients and two imipenem patients. Major side effects in both groups were gastrointestinal and central nervous system-related symptoms. In terms of clinical and bacteriological efficacy and safety, there was no statistical difference between the two groups, and both groups gave good to excellent results for bacterial infections that were difficult to treat. PMID- 3324955 TI - Trimethoprim resistance. PMID- 3324958 TI - Energy-dependent efflux mediated by class L (tetL) tetracycline resistance determinant from streptococci. AB - The class L (TetL) tetracycline resistance determinant from streptococci specified resistance and an energy-dependent decreased accumulation of tetracycline in both Streptococcus faecalis and Escherichia coli. Using E. coli, we showed that the reduced uptake resulted from active efflux. The streptococcal class M determinant, known to render the protein synthesis machinery of S. faecalis resistant to tetracycline inhibition, did not alter tetracycline transport in either host. PMID- 3324957 TI - Value of antibiotic levels in serum and cardiac vegetations for predicting antibacterial effect of ceftriaxone in experimental Escherichia coli endocarditis. AB - In a rabbit model of Escherichia coli endocarditis, we studied the penetration into infected vegetations and the antibacterial effect of ceftriaxone. Ceftriaxone was given at different dosages, alone or with an interfering agent, diclofenac, a nonsteroidal anti-inflammatory drug, to determine the predictive value of the antibiotic levels in serum or infected vegetations on the antibacterial efficacy. Diclofenac increased the serum terminal half-life of ceftriaxone and increased its extravascular diffusion in tissue cage fluid, as well as in infected vegetations, allowing us to obtain various antibiotic concentrations in the infected site. Two hours after the fourth injection, around the time of peak level in serum, we observed a linear relationship between (i) serum and local antibiotic levels in vegetations, (ii) local antibiotic levels in a range of 142 to 600 X MBC and bacterial titer (log10 CFU/g) in vegetations, and (iii) serum antibiotic levels in a range of 800 to 1,400X MBC and bacterial titer in vegetations. In vivo, antibacterial effect was obtained only with high antibiotic levels in vegetations (greater than or equal to 220X MBC). This was confirmed by incubating vegetations sampled from infected animals in rabbit serum containing ceftriaxone (ex vivo experiment). Given once daily at a therapeutic dosage (30 mg/kg) for 4 days, ceftriaxone exhibited good efficacy (log10 CFU/g of vegetation = 2.41 +/- 2.7 versus 7.41 +/- 0.92 in control animals) and prevented regrowth of bacteria until 24 h after the last injection. We concluded that (i) provided the dose is sufficient, a long-acting cephalosporin can prove effective in severe gram-negative infections even when given infrequently, and (ii) serum antibiotic levels around the peak value, reflecting high effective local levels, could predict the therapeutic efficacy and represent a simple test to monitor the clinical course of a severe infectious process. PMID- 3324959 TI - Effects of beta-lactam antibiotics on proliferating eucaryotic cells. PMID- 3324960 TI - Cryptic tetracycline resistance determinant (class F) from Bacteroides fragilis mediates resistance in Escherichia coli by actively reducing tetracycline accumulation. AB - Escherichia coli bearing a cryptic tetracycline resistance determinant from Bacteroides fragilis expressed low-level constitutive resistance to tetracycline under aerobic, but not anaerobic, growth conditions and accumulated less tetracycline aerobically than did isogenic susceptible cells. This decreased uptake was energy dependent and reversible by increased concentrations of tetracycline, suggesting a saturable carrier-mediated active efflux mechanism. Decreased uptake was not seen when the cells were grown and assayed anaerobically. Other tetracycline resistance determinants (classes A to E) isolated from gram-negative enteric bacteria expressed resistance and generated active efflux of tetracycline under anaerobic as well as aerobic conditions. When the Bacteroides determinant was placed in the same cell with any of the class A to E tetracycline resistance determinants, there was an increase in resistance under aerobic conditions of as much as 48% more than was projected by adding the resistances expressed by the determinants individually. In cells bearing the class A determinant together with the Bacteroides determinant, saturation of the active efflux system required over twofold more exogenous tetracycline than did cells bearing the class A determinant alone. We have designated this new tetracycline resistance determinant class F. PMID- 3324961 TI - Comparative in vitro and in vivo evaluation of N-D-ornithyl amphotericin B methyl ester, amphotericin B methyl ester, and amphotericin B. AB - N-D-Ornithyl amphotericin B methyl ester (O-AME), a semisynthetic derivative of amphotericin B methyl ester (AME), was compared with amphotericin B (AMB) and AME. In vitro, O-AME was more active than the other two against Candida spp. and other fungi and was only slightly affected by inoculum size, addition of serum, or changes in pH. In vivo, the dose of O-AME required to produce a 10,000-fold reduction of Candida albicans in a mouse kidney infection was similar to that of AMB and 1/10 that of AME. After intravenous treatment of infected mice and rats and subcutaneous treatment of mice, average 50% protective doses for O-AME and AMB were similar. Acute intravenous 50% lethal doses in mice indicated that O-AME was one-ninth as toxic as AMB but twice as toxic as AME. Acute renal function tests in rats indicated that Sch 28191 was less than 1/10 as toxic as AMB and slightly more toxic than AME. On this basis, the calculated advantage relative to AMB (with AMB equal to 1) was 8 for O-AME and 1.5 for AME. PMID- 3324962 TI - Comparative activities of ciprofloxacin and ceftazidime against Klebsiella pneumoniae in vitro and in experimental pneumonia in leukopenic rats. AB - The antibacterial activities of ciprofloxacin and ceftazidime against Klebsiella pneumoniae in vitro and in vivo were compared. Although there was only a minor difference between the MBCs of both drugs, the bacterial killing rate of ciprofloxacin in vitro was very fast in comparison with that of ceftazidime. Similarly, the intravenous administration of ciprofloxacin at 1 h after bacterial inoculation resulted in effective bacterial killing in the lungs of leukopenic rats. This killing was dose dependent, in contrast to the dose-independent bactericidal effect of ceftazidime. The high antibacterial activity of ciprofloxacin in the lungs as compared with that of ceftazidime was also reflected in its therapeutic efficacy in K. pneumoniae pneumonia and septicemia in leukopenic rats when these infections were treated at 6-h intervals over 4 days, starting at 5 h after bacterial inoculation. Concentrations of ciprofloxacin and ceftazidime in lung tissue were not significantly different. Regarding the antibacterial activity of both drugs against K. pneumoniae in relation to the bacterial growth rate in vitro and in the lungs of leukopenic rats, ciprofloxacin killed K. pneumoniae organisms that were not actively growing, whereas ceftazidime did not. In addition, it was demonstrated that when the intravenous administration of antibiotic was delayed from 1 h up to 24 h after bacterial inoculation, ceftazidime lost its antibacterial activity in the lungs and blood of leukopenic rats, whereas ciprofloxacin was still very effective. These data suggest that the capacity of an antibiotic to kill bacteria at a slow growth rate may be relevant for its therapeutic effect in established infections, in which slowly growing bacteria form a substantial part of the total bacterial population. PMID- 3324963 TI - Correction for bacterial loss in in vitro dilution models. AB - A new method to correct for bacteria lost to dilution in in vitro kinetic models is presented which includes the influence of the stationary bacterial growth phase. The method imposes an upper limit on bacterial density, in contrast to previous methods. PMID- 3324965 TI - Circadian regulation of feeding in rats: suprachiasmatic versus ventromedial hypothalamic nuclei. AB - The role of the suprachiasmatic nuclei as a major component of a specific circadian system controlling feeding periodicity is reviewed. Evidence is presented supporting the assumption that the ventromedial hypothalamus and the suprachiasmatic nucleus may act as a constant (tonic) regulator and a circadian modulator respectively of feeding in rats. It is concluded that a specific circadian system differing from the metabolic control mechanism superimposes the circadian periodicity of feeding. A model is put forward for the possible functional relationships between circadian and metabolic (homeostatic) control mechanisms of feeding in rats. PMID- 3324964 TI - Is it morphologic type or physiologic state that governs susceptibility of Candida albicans to clotrimazole kill? PMID- 3324966 TI - Increased production of aspartase in Escherichia coli K-12 by use of stabilized aspA recombinant plasmid. AB - Recombinant plasmid pYT471, which consists of the aspartase gene (aspA) and the multicopy vector pBR322, was lost from cells of Escherichia coli K-12 at high frequencies in medium in which aspartase was abundantly formed due to release from catabolite repression. This plasmid loss was not completely prevented by the selective pressure of antibiotic addition. To increase the stability of the aspA plasmid, pNK101 (pBR322::aspA-par) was constructed by using the partition locus (par) derived from the low-copy vector pSC101. In E. coli K-12 cells, pNK101 was lost at a frequency as low as 0.4% per cell generation in nonselective medium, whereas pYT471 was lost at a frequency as high as 8.5%. Cells harboring this stable plasmid produced ca. 30-fold more aspartase than did cells harboring the unstable plasmid after 30 cell generations. Thus, we could increase aspartase production by stabilizing the aspA recombinant plasmid. PMID- 3324967 TI - Enumeration of Vibrio cholerae O1 in Bangladesh waters by fluorescent-antibody direct viable count. AB - A field trial to enumerate Vibrio cholerae O1 in aquatic environments in Bangladesh was conducted, comparing fluorescent-antibody direct viable count with culture detection by the most-probable-number index. Specificity of a monoclonal antibody prepared against the O1 antigen was assessed and incorporated into the fluorescence staining method. All pond and water samples yielded higher counts of viable V. cholerae O1 by fluorescent-antibody direct viable count than by the most-probable-number index. Fluorescence microscopy is a more sensitive detection system than culture methods because it allows the enumeration of both culturable and nonculturable cells and therefore provides more precise monitoring of microbiological water quality. PMID- 3324968 TI - Metabolic activity of bacterial cells enumerated by direct viable count. AB - The direct viable count (DVC) method was modified by incorporating radiolabeled substrates in microautoradiographic analyses to assess bacterial survival in controlled laboratory microcosms. The DVC method, which permits enumeration of culturable and nonculturable cells, discriminates those cells that are responsive to added nutrients but in which division is inhibited by the addition of nalidixic acid. The resulting elongated cells represent all viable cells; this includes those that are culturable on routine media and those that are not. Escherichia coli and Salmonella enteritidis were employed in the microcosm studies, and radiolabeled substrates included [methyl-3H]thymidine or [U 14C]glutamic acid. Samples taken at selected intervals during the survival experiments were examined by epifluorescence microscopy to enumerate cells by the DVC and acridine orange direct count methods, as well as by culture methods. Good correlation was obtained for cell-associated metabolic activity, measured by microautoradiography and substrate responsiveness (by the DVC method) at various stages of survival. Of the cells responsive to nutrients by the DVC method, ca. 90% were metabolically active by the microautoradiographic method. No significant difference was observed between DVC enumerations with or without added radiolabeled substrate. PMID- 3324969 TI - Recovery of a marker strain of Escherichia coli from ozonated water by membrane filtration. AB - Selective and nonselective growth media were evaluated at two incubation temperatures, 35 and 44.5 degrees C, for the recovery of a nalidixic acid resistant marker strain of Escherichia coli ATCC 11775 by membrane filtration from ozonated 0.05 M phosphate buffer (pH 6.9). There were significantly fewer bacteria recovered with the standard m-FC agar when compared with the same growth medium prepared without bile salts and rosolic acid. This effect was particularly noticeable at the elevated incubation temperature of 44.5 degrees C. These findings are contrary to previous work which concluded that the standard American Public Health Association membrane filtration procedure is suitable for recovery of fecal coliform indicator bacteria from ozonated wastewater. PMID- 3324970 TI - Comparison of four membrane filter methods for fecal coliform enumeration in tropical waters. AB - Four membrane filter methods for the enumeration of fecal coliforms were compared for accuracy, specificity, and recovery. Water samples were taken several times from 13 marine, 1 estuarine, and 4 freshwater sites around Puerto Rico, from pristine waters and waters receiving treated and untreated sewage and effluent from a tuna cannery and a rum distillery. Differences of 1 to 3 orders of magnitude in the levels of fecal coliforms were observed in some samples by different recovery techniques. Marine water samples gave poorer results, in terms of specificity, selectivity, and comparability, than freshwater samples for all four fecal coliform methods used. The method using Difco m-FC agar with a resuscitation step gave the best overall results; however, even this method gave higher false-positive error, higher undetected-target error, lower selectivity, and higher recovery of nontarget organisms than the method using MacConkey membrane broth, the worst method for temperate waters. All methods tested were unacceptable for the enumeration of fecal coliforms in tropical fresh and marine waters. Thus, considering the high densities of fecal coliforms observed at most sites in Puerto Rico by all these methods, it would seem that these density estimates are, in many cases, grossly overestimating the degree of recent fecal contamination. Since Escherichia coli appears to be a normal inhabitant of tropical waters, fecal contamination may be indicated when none is present. Using fecal coliforms as an indicator is grossly inadequate for the detection of recent human fecal contamination and associated pathogens in both marine and fresh tropical waters. PMID- 3324971 TI - Testing for bacterial resistance to arsenic in monitoring well water by the direct viable counting method. AB - Direct viable counting of metal-resistant bacteria (DVCMR) has been found to be useful in both enumerating and differentiating metal-resistant and metal sensitive strains of bacteria. The DVCMR bioassay was used to detect effects of low and high concentrations of arsenic and arsenicals on bacterial populations in groundwater. The level of resistance of the bacterial populations to arsenate was determined by the DVCMR bioassay, and the results showed a linear correlation with the total arsenic concentrations in the monitoring well water samples; no correlation was observed by culture methods with the methods employed. Bacteria resistant to 2,000 micrograms of arsenate per ml were isolated from all monitoring well water samples studied. Strains showed similar antibiotic and heavy-metal profiles, suggesting that the arsenic was not a highly selective pressure for arsenic alone. The monitoring well water samples were amended with arsenate and nutrients to determine the biotransformation mechanisms involved. Preliminary results suggest that bacteria indigenous to the monitoring well water samples did not directly transform, i.e., precipitate or volatilize, dissolved arsenic. It was concluded that arsenic contamination of the groundwater can be monitored by the DVCMR bioassay. PMID- 3324972 TI - Cerebral blood flow velocity variability in infants receiving assisted ventilation. AB - Cerebral blood flow velocity was measured using Doppler ultrasonography in 20 babies who weighed less than 2500 g at birth and who were receiving assisted ventilation; their patterns of spontaneous respiration were recorded simultaneously. The babies were induced to breathe synchronously or asynchronously with the ventilator by manipulating the inspiratory and expiratory time settings. The variability of cerebral blood flow velocity (coefficient of variation) was calculated from the area of the maximum Doppler frequency shift envelope for 10 cardiac cycles from 211 recordings made on 42 occasions, and was greatest within 12 hours of birth after which it fell progressively over the next 48 hours. Variability of cerebral blood flow velocity was significantly greater when the infants were breathing out of synchrony with the ventilator (median 11%, interquartile range 8-14%) than when they were either apnoeic (median 5%, 3-7%), or breathing synchronously with the ventilator (median 5%, 3-6%). PMID- 3324973 TI - Inspiratory times when weaning from mechanical ventilation. AB - Two inspiratory times (0.5 and 1.0 seconds) were compared when weaning infants from mechanical ventilation. The shorter inspiratory time was associated with significant increases in minute volume and reduction in active expiration. PMID- 3324975 TI - Initial lesions of HIV-related Kaposi's sarcoma--a histological, immunohistochemical, and ultrastructural study. AB - Kaposi's sarcoma (KS) in human immunodeficiency virus infection (HIV) has become a rather frequent manifestation of the previously rare disease with fatal outcome. Initial lesions of KS were studied by means of histopathology, immunohistology, and electron microscopy in order to define the earliest alterations. The histopathological changes of initial lesions were distinct, consisting of (1) discrete proliferation of capillary vessels, (2) dissection of collagen by proliferating spindle cells which formed slits, (3) atypical spindle cells arranged in an Indian file pattern, and (4) the lack of any inflammatory cellular infiltrate. Double staining with antibodies against vimentin and immunohistochemical markers for endothelial cells revealed that slits forming vimentin-positive spindle cells displayed laminin, factor VIII, and PAL-E. Atypical vimentin-positive spindle cells arranged in an Indian file pattern inconsistently expressed laminin and factor VIII, but not PAL-E. KS cells rarely stained with the lectin UEA I, not even in case of less advanced dedifferentiation. Electron microscopy showed gradual transformation between spindle cells forming slits and those having lost the ability to form incomplete vessel walls. The present findings support the view that KS develops from the endothelial cells of the blood vessels. The proliferation of atypical endothelial cells as early as in initial lesions and the lack of inflammation favors the primary neoplastic genesis of KS. PMID- 3324974 TI - Granulocyte-activating mediators (GRAM). II. Generation by human epidermal cells- relation to GM-CSF. AB - In the present study we investigated the capability of human epidermal cells to generate granulocyte-activating mediators (GRAM). It could be shown that human epidermal cells as well as an epidermoid carcinoma cell line (A431) produce an epidermal cell-derived granulocyte-activating mediator (EC-GRAM) which stimulates human granulocytes to release significant levels of toxic oxygen radicals as measured by a lucigenin-dependent chemiluminescence (CL). For further characterization of EC-GRAM the A431 cell line was used. Supernatants of A431 cells usually contained maximal EC-GRAM levels within 24 h of incubation. Factor production was enhanced by bacterial lipopolysaccharide (LPS), but not by silica particles and PHA. Moreover, freeze-thaw lysates of A431 cells and extracts of heat-separated human epidermis contained significant levels of EC-GRAM. Preincubation of granulocytes with EC-GRAM resulted in an enhanced response to subsequent stimulation with the chemotactic peptide f-met-phe. In contrast EC GRAM did not affect the response to PMA or zymosan particles. However, EC-GRAM treated granulocytes were unresponsive to restimulation with EC-GRAM. Upon high performance liquid chromatography (HPLC) gel filtration EC-GRAM eluted within two major peaks exhibiting a molecular weight of 17 kD and 44 kD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3324976 TI - Bullous pemphigoid blister fluids influence the density distribution of eosinophils. PMID- 3324977 TI - Bacterial synergy in pelvic inflammatory disease. AB - Polymicrobial aerobic and anaerobic flora are responsible for pelvic inflammatory disease (PID). The most frequent pathogens appear to be Neisseria gonorrhoea and anaerobic bacteria (most commonly anaerobic cocci and Bacteroides sp.). Recent studies have demonstrated the recovery of Chlamydia trachomatis in up to a third of these infections. Although N. gonorrhoea is frequently recovered from cervical cultures, it is less commonly recovered from intra-abdominal sites. Recent studies have demonstrated the in-vivo synergistic relationship between N. gonorrhoeae and Bacteroides fragilis. The growth of each component of the mixed infection was enhanced when these were present together in an abscess. Furthermore, the emergence of encapsulated strains was enhanced in these infections. This synergy enables the organisms to cause more severe local and systemic damage to the host. Therapeutic intervention should include the use of antimicrobial agents effective against both the aerobic and anaerobic components of the mixed infection. Unless such therapy is given, the infection may persist. It is also recommended to use antimicrobials that possess synergy between them against the bacterial pathogens. Agents effective against the anaerobic pathogens are metronidazole, clindamycin and cefoxitin. Antimicrobials effective against the Gram-positive aerobic pathogens and N. gonorrhoeae are spiramycin and penicillins. Aminoglycosides or third generation cephalosporins are effective against Gram-negative enterics. The combination of metronidazole and spiramycin has shown to be synergistic against mixed infections of Bacteroides sp. and N. gonorrhoeae. PMID- 3324979 TI - Comparison of the results of vaginal and abdominal follicle scans. AB - The hormonal profile and sonographical assessing of the number and size of the follicles are important in hyperstimulated cycles. Follicular imaging obtained by abdominal scanning may be distorted by echoes from the intestine or by unfavourable location of the ovaries and patients must have a full bladder. We compared the number and size of the follicles at abdominal sonography with the results obtained by vaginal sonography in 37 patients. Vaginal sonography showed more follicles than abdominal sonography because of improved imaging of small follicles on early days of cycle. This might help one to tailor the hyperstimulation to an individual's endocrine response. PMID- 3324980 TI - [Sweet's syndrome and myeloid leukemia. Apropos of a case]. PMID- 3324978 TI - Transmission rate of Ureaplasma urealyticum, Mycoplasma spp., Gardnerella vaginalis, B-streptococci, Candida spp. and Chlamydia trachomatis from the mother to the newborn. AB - In a preliminary study of the transmission rate of Ureaplasma urealyticum, Mycoplasma species, Gardnerella vaginalis, B-Streptococci, Candida species and Chlamydia trachomatis from the mother to the newborn, swabs were taken from 45 parturients and their neonates and cultured by suitable methods. Out of 30 parturients with a positive culture, 8 harboured more than one microorganism investigated. U. urealyticum was found in 11 newborn and all of them had a positive mother. Candida spp. were found in 4 newborn, but 3 of these had a negative mother. G. vaginalis was detected in only 1 infant and the mother was negative. C. trachomatis was not isolated from any mother but was present in 2 newborn infants. Thus only U. urealyticum showed clear evidence of transmission from mother to baby. PMID- 3324981 TI - [Inflammatory fibrous histiocytoma of the stomach. Apropos of a case of xanthogranuloma?]. PMID- 3324982 TI - [Clear cell carcinoma of the thymus. Observation of a case of this exceptional variety of malignant thymoma]. PMID- 3324984 TI - Sperm and seminal plasma antigens from autoimmune men induce immunological infertility. AB - Adult male rabbits were immunized with normal saline (controls), sperm extracts from 2 autoimmune men, seminal plasmas from the same autoimmune men, sperm extract from a fertile nonautoimmune man, and seminal plasma from the same fertile nonautoimmune man. All the sperm donors were free from infections. Rabbits immunized with fertile men's sperm extract and seminal plasma had significantly elevated postimmunization hemagglutinating but not cytotoxic sperm antibodies and reproduced normally. Rabbits immunized with autoimmune men's sperm and seminal plasma antigens developed high titers of cytotoxic and hemagglutinating sperm antibodies in their serum and seminal plasma and their reproduction was markedly reduced. Their sera and seminal plasma reduced motility of sperm from a normal donor. The immune responses were confirmed by electron microscopic immunocytochemistry. This technique revealed membrane-bound endogenous IgG on sperm from only those rabbits immunized with sperm extracts from autoimmune men. These antisera reacted against a protein in the 58,000 D range; antisera to fertile man's sperm extract reacted against three proteins with molecular weights of 15,000, 18,400, 25,000, and 44,000 D, as judged by Western blot. Rabbit antisera to seminal plasma from autoimmune men reacted against several proteins; additionally, it detected two proteins with 43,000 and 68,000 molecular weight detected by antiserum to fertile man's seminal plasma. Sperm and seminal plasma antigens from autoimmune men are different in their elicited immunogenic responses from those of fertile nonautoimmune men. These responses are relevant to infertility. PMID- 3324985 TI - [70th anniversary of the great Socialist October Revolution]. PMID- 3324983 TI - Kallikrein in the male reproductive system. AB - Male genital organs were stained by the peroxidase-antiperoxidase (PAP) method to know the location of kallikrein. Sertoli cells of the testis, epithelial cells that existed from the body to the tail of the epididymis, and glandular cells of the prostate were specifically stained showing that kallikrein was produced in these cells. The concentration of kallikrein in the semen specimens mainly from patients with male sterility and from those who were subjected to vasoligation and in the prostatic fluid specimens from normal controls were measured by radioimmunoassay (RIA). The results of column chromatography suggested that kallikrein combined with the other substances to form a high molecular compound in the semen. The kallikrein level in the semen from the normal control was 40.4 +/- 21.3 ng/ml, which was more than 10 times that in the blood. The value tended to increase with the decrease of the number of spermatozoa. The kallikrein level in the semen from patients with azoospermia was 74.2 +/- 23.5 ng/ml, which was significantly higher than that of the normal control. There was no significant correlation between the kallikrein level and the sperm motility. The kallikrein level in the semen from the patients subjected to vasoligation, which did not contain the semen originated from the testis, and that in the prostatic fluid from the normal control were 20-28 ng/ml. That amount was considered to be secreted from the prostate. The oral administration of hog kallikrein tablet augmented seminal human kallikrein and Acid-P secretion. Moreover, an improvement of seminalysis was observed following long term administration of 600 U/day of hog kallikrein in the male infertile patients. This drug might be useful to treat the male infertile patients with this disorder. PMID- 3324986 TI - [Important points in pathogen-caused diseases in cattle and swine and implications for immunoprophylaxis]. PMID- 3324987 TI - [The use of genetic engineering methods in virology]. PMID- 3324988 TI - [Mechanism of retrovirus-induced malignant transformation]. PMID- 3324989 TI - [The state of knowledge of the viral etiology of human tumors]. PMID- 3324990 TI - Bone matrix and marrow versus cancellous bone in rabbit radial defects. AB - Implants of demineralized bone matrix induce new bone formation. In order to estimate the possible clinical usefulness of this phenomenon, autologous cancellous bone grafts were compared with composite grafts of bone matrix and marrow. Cancellous bone from the tuber ischii of the rabbit was transplanted to a preformed radial defect in the same animal. On the opposite side, a similar defect was filled with a mixture of either allogenous or autogenous bone-matrix particles and autogenous bone marrow. After 25 days, calcium 45 was injected intravenously. Three days later the animals were killed. Standardized segments of the rabbit's forearms, containing the middle of the defect, were cut out, ashed, and analyzed for 45Ca activity. No side difference in 45Ca deposition was found. The callus ash weight of the allogenous matrix-transplanted side was approximately 60% of that of the cancellous bone side. This side difference of ash weights corresponds to the estimated initial mineral content of the cancellous graft. Nontransplanted defects had very low ash weight and 45Ca activity. Thus, in the rabbit, composite grafts of bone matrix and marrow produce a bone yield comparable to that of cancellous bone. PMID- 3324991 TI - What is the efficacy of "soft" and "mid" lasers in therapy of tendinopathies? A double-blind study. AB - The efficacy of "athermic" lasers (HeNe lambda = 632.8 nm and IR diode lambda = 904 nm) in the treatment of tendinopathies was investigated in a randomized double-blind study. On 10 consecutive days, 64 patients (32 therapy, 32 placebo) were treated for 15 minutes each with a switched-on or switched-off laser under otherwise identical conditions. The extent of movement in involved joints (neutral 0 method) and rating on a pain scale for resting pain, movement pain, and pressure pain before treatment, after treatment, and 2 weeks after conclusion of therapy, as well as infrared thermography, served to check therapy. After the end of therapy, a significant reduction (P = less than 0.001) of 50% was shown for resting pain as well as reductions of 30% for movement and 30% for pressure pain. This result was identical in the therapy group and in the placebo group. There was also no indication of a different result of therapy between the therapy and placebo groups with regard to the thermographic control and the extent of movement. The breakdown of the data in terms of age, sex, and duration of disease did not provide any indications of different results for placebo or therapy. It was striking that the patients who reported sensations during or after the treatment (irrespective of whether pleasant or unpleasant) had a greater reduction of pain than the patients without sensations. This laser therapy thus did not show any effect above and beyond that in the untreated group in our double-blind clinical study. PMID- 3324992 TI - The specificity of serum antibodies to the haemagglutinin of influenza B viruses induced by vaccination. PMID- 3324993 TI - Natural inhibitors of complement. II. Isolation of pokeweed complement inhibitor(s) by ion exchange. PMID- 3324994 TI - Improved method of Yersinia enterocolitica isolation in feces. PMID- 3324996 TI - [Assessment of the scientific legacy of J. E. Purkinje in the USSR]. PMID- 3324995 TI - Possible relationship between the incidence of SSPE and some inflammatory syndromes triggered by parasites and bacteria. PMID- 3324998 TI - [Improved histochemical demonstration of adrenergic nerve elements in a solution of glyoxylic acid with the aid of dimethyl sulfoxide (DMSO)]. PMID- 3324997 TI - [Theoretician of anthropological anatomy (on the centenary of the birth of M. A. Gremiatskii)]. PMID- 3324999 TI - [Current concepts of the structure and functions of the lymph node cortex]. PMID- 3325000 TI - [Emergencies in peptic gastroduodenal ulcers]. AB - The authors present an objective review of the main emergencies regarding peptic ulcer disease, gastric and duodenal. The complications, perforation, bleeding and pyloric stenosis, are dealt with in detail, regarding diagnosis and best therapeutic orientation, either clinical or surgical. PMID- 3325001 TI - An unusual presentation of herpes gestationis. PMID- 3325002 TI - Mermaid foetus: a rare case. PMID- 3325003 TI - Clinical significance of CA125 and its assessment with an enzyme immunoassay. PMID- 3325004 TI - Selection for dental practice of chemical disinfectants and sterilants for hepatitis and AIDS. PMID- 3325006 TI - The diagnosis and management of cerebral vascular disease. PMID- 3325005 TI - Automated health testing. PMID- 3325007 TI - Abdominal aortic aneurysms. Diagnosis and management. PMID- 3325008 TI - Middle ear effusion. PMID- 3325009 TI - Doppler ultrasound velocity waveform analysis. PMID- 3325011 TI - Recent advances in bone marrow transplantation. AB - The major barriers to successful bone marrow transplantation (BMT) are graft versus-host disease (GVHD), infection, rejection and relapse. The combination of methotrexate and cyclosporin is significantly better than either alone in controlling GVHD. Removal of T cells from donor marrow prior to BMT has also decreased GVHD significantly, but a 5-10% rejection rate occurs and an increased relapse risk is being reported by some centres. Cyclosporin is valuable in the treatment of both acute and chronic GVHD. Interstitial pneumonitis due to cytomegalovirus (CMV) is a major cause of mortality. Protection can be provided with CMV hyperimmune globulin and also by the avoidance of blood donors who are CMV antibody positive. Fractionated total body irradiation is associated with decreased toxicity compared to single dose. There is a 75% 4 year disease-free survival following BMT for acute non-lymphoblastic leukemia in first remission, a 50% survival for acute lymphoblastic leukemia in second remission and an 88% survival for chronic myeloid leukemia in chronic phase. BMT for beta-thalassaemia major in young patients without organ dysfunction cures 80% of patients and identical results are achieved for severe aplastic anaemia when BMT is undertaken prior to blood product transfusion. PMID- 3325010 TI - Evidence against an immunogenetic basis for diabetes in chronic pancreatitis. AB - A possible immunogenetic basis for diabetes in chronic pancreatitis was explored by studying 19 patients with both disorders, most of whom required treatment with insulin. In contrast to patients with insulin-dependent (Type 1) diabetes, patients with diabetes and chronic pancreatitis had residual beta cell function but blunted C-peptide responses to intravenous glucagon, absence of circulating islet cell antibodies, and HLA-DR types similar to control subjects and patients with chronic pancreatitis without diabetes. Diabetes complicating chronic pancreatitis is therefore not associated with the biochemical or immunogenetic markers characteristic of Type 1 diabetes. PMID- 3325013 TI - The heavenly twins: useful anatomic landmarks in C.T. and ultrasound of the abdomen. PMID- 3325012 TI - Epidemiology and prevention of invasive Haemophilus influenzae type b infection. AB - The use of rifampicin prophylaxis is recommended in close contacts of individuals with invasive Haemophilus influenzae type b infection if they include a child less than 4 years old in whom the risk of secondary infection is relatively high. In practice, delays in administration of rifampicin, contra-indications to its use and the difficulty of identifying all contacts at risk can reduce significantly its efficacy. Only 1-2% of cases of H. influenzae type b diseases are attributable to known contact and, at best, rifampicin prophylaxis can have little impact on the incidence. In the USA, one in 200 children less than 5 years old is affected. The incidence is probably similar in Australia but there are local differences which could affect the value of preventative measures. The vaccine recently licensed in the USA is not effective in children less than 18-24 months of age in whom the incidence of invasive H. influenzae type b infection, other than epiglottitis, is highest. Nevertheless, it could prevent more than 30% of cases if given to children at the age of 24 months. Vaccines effective in younger infants should become available soon. The best chance of prevention is by the optimal use of both rifampicin prophylaxis and immunization. PMID- 3325014 TI - Atypical target pattern: sonography in GIT lesions. PMID- 3325015 TI - Cavernous haemangioma of the liver. A diagnostic problem. PMID- 3325016 TI - Percutaneous real-time ultrasonic guided biopsy in the diagnosis of deep-seated, non-palpable intra-abdominal masses (initial experience). PMID- 3325017 TI - Outcome of singleton infants delivered vaginally or by caesarean section at 23 to 28 weeks' gestation. AB - The survival and impairment rates of 276 inborn singleton infants of 23-28 weeks' gestation were reported according to route of delivery and mode of presentation. The Caesarean section rate was 29% overall, ranging from 13% at 25 weeks to 46% at 28 weeks. In the vertex group, no significant difference in survival or impairment rate was found between Caesarean and vaginal births. In the non-vertex group, Caesarean births had a similar survival rate but a significantly lower impairment rate compared to vaginal births. For Caesarean births, no significant difference in survival or impairment rate was found between vertex and non-vertex groups. In contrast, for vaginal births, the mode of presentation was important: the non-vertex group had a significantly lower survival rate and higher impairment rate compared to the vertex group. We found no evidence to support the use of Caesarean section in extremely preterm infants with vertex presentation, except for recognized maternal or fetal indications. The findings in the non vertex group indicated that there is a definite need for a randomized clinical trial to investigate the possible benefits of Caesarean section in extremely preterm infants with non-vertex presentation. PMID- 3325019 TI - Metronidazole. PMID- 3325018 TI - Cone biopsy of the cervix: does surgical technique influence cytological follow up? AB - A 10-year experience of cone biopsy of the cervix was reviewed to determine whether the surgical method used delayed the diagnosis of recurrent disease. Although there is a trend to selective ablation of cervical intraepithelial neoplasia, cone biopsy is a necessary adjunct to the colposcopist and remains the technique used by many gynaecologists. Two surgical techniques were compared; 1) Sturmdorf sutures, where the denuded cervical stump was covered by squamous epithelium 2) Interrupted vertical sutures, where the cervical epithelium was not covered. There was a 15% incidence of recurrent disease which was related to the completeness of initial excision and the age of the patient. The surgical technique employed did not influence the future cytological follow-up nor delay the diagnosis of recurrent disease. PMID- 3325021 TI - Temperament and psychiatric disorder: the genetic contribution to behaviour in childhood. AB - The studies stemming from the New York longitudinal study of temperament in childhood are summarised and conceptual difficulties and problems arising from them are described. An alternative model of temperament provided by Buss and Plomin is also considered. Finally, a new typology of temperament is proposed. It is based on the suggestion that ordinary, non-pathological behaviours, in extreme form, can be viewed as manifestations of emotional disorder, hyperactivity and antisocial disorder. Empirical evidence derived both from twin studies and from epidemiological investigations is put forward to support this view. PMID- 3325020 TI - Cyclopia with trisomy 13. PMID- 3325022 TI - Stress and coronary heart disease. PMID- 3325023 TI - Assessing dementia. Part II: Clinical, functional, neuropsychological and social issues. AB - Comprehensive assessment of the dementing person entails looking beyond syndromal diagnosis to broader aspects of the individual's functioning and circumstances. Systematic attempts are being made to conceptualize the stage, severity and sub type of dementia and these may prove useful in daily practice. Clinical aspects of a broader assessment include attention to possible coexisting psychiatric syndromes and the disruptive behavioural changes common in dementia. In addition, alternative perspectives to the medical model can contribute valuable information for future planning. Functional assessment can delineate lost abilities that limit the person's adaptive capacity and indicate retained skills necessary for independent living. The neuropsychological approach can identify spared abilities and specific impairments, as well as quantifying changes over time. Attention to social issues can clarify the strengths and deficiencies of the support network and define the burdens of caring. A general approach, which emphasises the need for dementia assessment to be comprehensive, multidisciplinary, naturalistic, intervention oriented, practical and longitudinal, is proposed. This assessment approach is closely linked to the most important role of the clinician, that of continuing care and management. PMID- 3325024 TI - Did schizophrenia exist before the eighteenth century? AB - Madness has resisted a satisfactory categorisation for 2,000 years or more. During the last century attempts to define and understand schizophrenia as an entity within that disorder have failed. This article explores some of the reasons why this may have happened, in particular considering whether the syndrome that we now call schizophrenia has changed in recent years and whether it existed at all four centuries ago. It is based on the author's experience and upon contemporary case histories. PMID- 3325025 TI - Lessons from the insulin story in psychiatry. AB - For nearly 20 years, from the mid-1930s until the mid-1950s, early cases of schizophrenia were treated, and surprisingly successfully treated, by deep insulin coma therapy. This paper is an attempt to explore what, if any, lessons there are to be gained for us 30 years later from a treatment regime that turned out to have nothing to do with insulin per se. Such lessons as there may be from our recent historical past may help us to foster our critical acumen and commonsense as we try in our daily practice to understand how we can best help our patients in safety. PMID- 3325026 TI - Lithium in depression: a review of the antidepressant and prophylactic effects of lithium. AB - The therapeutic effects of lithium in depression are reviewed. The acute antidepressant effect of lithium alone is neither as impressive nor as predictable as its antimanic action, nor is it equivalent to that of tricyclic antidepressants. In patients who are 'refractory' to tricyclics or monoamine oxidase inhibitors, combined treatment with lithium may augment antidepressant response. Lithium is an effective prophylactic treatment in both unipolar and bipolar disorder and in the latter is the drug of choice. Aspects of monitoring, such as range of therapeutic plasma levels, dosage regimen and adverse effects, are discussed. Current evidence suggests that, in patients who fail to respond to lithium or are unable to tolerate side-effects, carbamazepine should be considered. PMID- 3325027 TI - Evolution of longevity in animals. A comparative approach. Proceedings of the 34th Brookhaven Symposium in Biology on Aging processes in animals. October 19 22, 1986, Upton, New York. Dedicated to George Sacher. PMID- 3325028 TI - Scaling of maximal lifespan in mammals: a review. PMID- 3325030 TI - [Review of the history of veterinary medicine: the honorary promotion of Emil Abderhalden in 1937]. PMID- 3325029 TI - Decreased digitalis receptor activity in acute rejecting canine transplanted heart. AB - In the course of acute rejection, myocardial tissue undergoes massive transformation and we hypothetized that for digitalis-like substances, receptor binding characteristics might be altered. Ten canine heterotopic cardiac allografts were carried out and were harvested once rejection had developed (8-10 days post-transplant). Microsomal membrane fractions of those grafts and of native hearts were isolated. Radioligand binding studies were carried out in a medium containing 5 mM Tris PO4, 50 mM Tris HCl, 5 mM MgCl2, pH 7.4 at 37 degrees C, using 3H-ouabain as the ligand. Saturation experiments (n = 10) indicate the presence of one homogeneous population of high affinity binding sites with an affinity constant (Kd) of 8-13 nM and a maximum binding capacity (Bmax) of 47 +/- 3.5 pmol/mg protein. Both saturation and competition binding studies illustrate the fact that acute rejection resulted in a significant decrease in Bmax (43%) without significant alteration in Kd value. These studies indicate that digitalis like substances might not exert significant inotropic activity during rejection, but this hypothesis must be confirmed by in vivo haemodynamic experiments. PMID- 3325031 TI - Influence of pesticides on the utilization of food. PMID- 3325032 TI - The importance of mycotoxins in foods. PMID- 3325033 TI - Immunochemical differentiation of glucose phosphate isomerase (GPI) allozymes of the mouse. AB - Polyclonal xenoantisera against mouse GPI-1B and GPI-1C were produced in rabbits and analyzed for their ability to recognize allozyme-specific determinants. These studies showed a high degree of serological similarity among the three allozymes of mouse glucose phosphate isomerase (GPI). However, GPI-1B and GPI-1C could be differentiated from GPI-1A as well as GPI-1A and GPI-1B from GPI-1C using quantitative solid-phase immunobinding assays. In addition, polyclonal and monoclonal alloantibodies specific for GPI-1C were produced in BALB/c (Gpi-1a/Gpi 1a) mice. As indicated by immunoblotting data, the allozyme specificity of rabbit antisera and monoclonal alloantibodies against GPI-1C is dependent on the native structure of that allozyme. PMID- 3325034 TI - Evidence for different kinases in thylakoid protein phosphorylation. AB - Thylakoid protein phosphorylation was facilitated in darkness by using the ferredoxin-NADPH system. CoCl2 and DBMIB (2,5-dibromo-3-methyl-6-isopropyl-p benzoquinone) were potent inhibitors of LHCP (light-harvesting chlorophyll binding protein) phosphorylation, but 3-(3,4-dichlorophenyl)-1,1-dimethyl-urea and atrazine had no significant effect. Differential effects on phosphorylation of the 9 kDa polypeptide and LHCP were observed in darkness with DBMIB and certain other inhibitors specific for Photosystem-II electron transport. Similarly, during illumination of intact chloroplasts or of the reconstituted chloroplast system, a differential action of bicarbonate was observed on the relative phosphorylation of the two proteins. The degree of phosphorylation of the 9 kDa polypeptide was increased in the presence of bicarbonate compared with its absence, whereas that of LHCP was relatively unchanged. Changes in the degree of phosphorylation of the 32 kDa polypeptide in these experiments did not correlate consistently with changes in phosphorylation of either LHCP or the 9 kDa polypeptide, although changes in the 32 kDa polypeptide more often paralleled phosphorylation of the 9 kDa polypeptide rather than the phosphorylation of LHCP. These observations suggest that the protein kinase that phosphorylates LHCP is distinct from that which phosphorylates the 9 kDa polypeptide. PMID- 3325035 TI - Fatty acid oxidation in bone tissue and bone cells in culture. Characterization and hormonal influences. AB - Fatty acid oxidation and its hormonal modulation were investigated in cultured rat calvaria and in cultivated cell populations. The latter were obtained from calvaria of newborn rats by sequential time-dependent digestion with collagenase, yielding eight cell populations: the early ones containing mainly fibroblasts, the middle ones being osteoblast-like, and late ones osteoblast-osteocyte-like. In calvaria, fatty acid oxidation was increased by adding 0.1 mM- and 1.0 mM palmitate to the medium, containing 10% (v/v) fetal-calf serum. No effect was found after parathyrin addition in vitro or when injected in vivo. All cell populations obtained by sequential digestion were found to oxidize palmitate, whereby the osteoblast-like cells showed a lower oxidation rate than the other populations. Both parathyrin and calcitonin had no effect on fatty acid oxidation. 1,25-Dihydroxycholecalciferol at 1-100 nM and 24,25 dihydroxycholecalciferol at 100 nM increased oxidation primarily in the population enriched with osteoblast-like cells. Insulin at 1.6 microM diminished it in the cell populations enriched with osteoblast-like cells and in the late bone-cell fraction. However, glucagon had no effect. The energy provided by fatty acid oxidation in this system is approx. 40-80% of glucose metabolism, suggesting that this event may be of importance in the energy metabolism of bone. PMID- 3325036 TI - Lysyl-tRNA synthetase from Escherichia coli K12. Chromatographic heterogeneity and the lysU-gene product. AB - In contrast with most aminoacyl-tRNA synthetases, the lysyl-tRNA synthetase of Escherichia coli is coded for by two genes, the normal lysS gene and the inducible lysU gene. During its purification from E. coli K12, lysyl-tRNA synthetase was monitored by its aminoacylation and adenosine(5')tetraphospho(5')adenosine (Ap4A) synthesis activities. Ap4A synthesis was measured by a new assay using DEAE-cellulose filters. The heterogeneity of lysyl-tRNA synthetase (LysRS) was revealed on hydroxyapatite; we focused on the first peak, LysRS1, because of its higher Ap4A/lysyl-tRNA activity ratio at that stage. Additional differences between LysRS1 and LysRS2 (major peak on hydroxyapatite) were collected. LysRS1 was eluted from phosphocellulose in the presence of the substrates, whereas LysRS2 was not. Phosphocellulose chromatography was used to show the increase of LysRS1 in cells submitted to heat shock. Also, the Mg2+ optimum in the Ap4A-synthesis reaction is much higher for LysRS1. LysRS1 showed a higher thermostability, which was specifically enhanced by Zn2+. These results in vivo and in vitro strongly suggest that LysRS1 is the heat-inducible lysU-gene product. PMID- 3325037 TI - Fluorescence and bioluminescence measurement of cytoplasmic free calcium. PMID- 3325038 TI - Characterization of the inositol 1,4,5-trisphosphate-induced Ca2+ release in pancreatic beta-cells. AB - Pancreatic beta-cells isolated from obese-hyperglycaemic mice released intracellular Ca2+ in response to carbamoylcholine, an effect dependent on the presence of glucose. The effective Ca2+ concentration reached was sufficient to evoke a transient release of insulin. When the cells were deficient in Ca2+, the Ca2+ pool sensitive to carbamoylcholine stimulation was equivalent to that released by ionomycin. Unlike intact cells, cells permeabilized by high-voltage discharges failed to generate either inositol 1,4,5-triphosphate (InsP3) or to release Ca2+ after exposure to carbamoylcholine. However, the permeabilized cells released insulin sigmoidally in response to increasing concentrations of Ca2+. Also in the absence of functional mitochondria these cells exhibited a large ATP dependent buffering of Ca2+, enabling the maintenance of an ambient Ca2+ concentration corresponding to about 150 nM even after several additional pulses of Ca2+. InsP3, maximally effective at 6 microM, promoted a rapid and pronounced release of Ca2+. The InsP3-sensitive Ca2+ pool was rapidly filled and lost its Ca2+ late after ATP depletion. The transient nature of the Ca2+ signal was not overcome by repetitive additions of InsP3. It was possible to restore the response to InsP3 after a delay of approx. 20 min, an effect which had less latency after the addition of Ca2+. These latter findings argue against degradation and/or desensitization as factors responsible for the transiency in InsP3 response. It is suggested that Ca2+ released by InsP3 is taken up by a part of the endoplasmic reticulum (ER) not sensitive to InsP3. On metabolism of InsP3, Ca2+ recycles to the InsP3-sensitive pool, implying that this pool indeed has a very high affinity for the ion. The presence of functional mitochondria did not interfere with the recycling process. The ER in pancreatic beta-cells is of major importance in buffering Ca2+, but InsP3 only modulates Ca2+ transport for a restricted period of time following immediately upon its formation. Thereafter the non-sensitive part of the ER takes over the continuous regulation of Ca2+ cycling. PMID- 3325039 TI - Metabolism of 1-aminoethylphosphinate generates acetylphosphinate, a potent inhibitor of pyruvate dehydrogenase. AB - The alanine analogue 1-aminoethylphosphinate [H3C-CH(NH2)-PO2H2] effectively inhibited anthocyanin synthesis in buckwheat hypocotyls and caused an increase in the concentrations of alanine and alanine-derived metabolites. Aminotransferase inhibitors partially alleviated the effects of the analogue. 1 Aminoethylphosphinate did not affect the growth of Klebsiella pneumoniae under anaerobic conditions, but under aerobic conditions it inhibited growth and caused the massive excretion of pyruvate. The analogue inhibited the pyruvate dehydrogenase complex in vitro in the presence of an aminotransferase activity. The transamination product of 1-aminoethylphosphinate, acetylphosphinate (H3C-CO PO2H2), was found to inhibit the pyruvate dehydrogenase complex in a time dependent reaction that followed first-order and saturation kinetics and required the presence of thiamin pyrophosphate. PMID- 3325040 TI - Vmax. activation of pp60c-src tyrosine kinase from neuroblastoma neuro-2A. AB - A kinetic analysis of the tyrosine-specific protein kinase of pp60c-src from the C1300 mouse neuroblastoma cell line Neuro-2A and pp60c-src expressed in fibroblasts was carried out to determine the nature of the increased specific activity of the neuroblastoma enzyme. In immune-complex kinase assays with ATP Mn2+ and the tyrosine-containing peptide angiotensin I as phosphoacceptor substrate, pp60c-src from the neuroblastoma cell line was characterized by a maximum velocity (Vmax.) that was 7-15-fold greater than the Vmax. of pp60c-src from fibroblasts. The neuroblastoma enzyme exhibited Km values for ATP (16 +/- 3 microM) and angiotensin I (6.8 +/- 2.6 mM) that were similar to Km values for ATP (25 +/- 3 microM) and angiotensin I (6.5 +/- 1.7 mM) of pp60c-src from fibroblasts. pp60v-src expressed in Rous-sarcoma-virus-transformed cells exhibited an ATP Km value (25 +/- 4 microM) and an angiotensin I Km value (6.6 +/ 0.5 mM) that approximated the values determined for pp60c-src in neuroblastoma cells and fibroblasts. These results indicate that the pp60c-src kinase from neuroblastoma cells has a higher turnover number than pp60c-src kinase from fibroblasts, and that the neural form of the enzyme would be expected to exhibit increased catalytic activity at the saturating concentrations of ATP that are found intracellularly. PMID- 3325041 TI - Changes in individual rates of pancreatic enzyme and isoenzyme biosynthesis in the obese Zucker rat. AB - Both alterations of enzyme content and a markedly decreased secretory response to selected physiological stimuli have been demonstrated previously in the pancreas of the obese Zucker rat. The purpose of the present investigation was to determine the degree to which alterations of enzyme content could be attributed to changes in enzyme biosynthesis. Amylase content of obese rats was decreased by 50%, whereas lipase and trypsinogens were significantly increased. However, the decrease in amylase content was less than might have been predicted from the rate of amylase biosynthesis (80% decrease), and the increases in content of trypsinogen(s) and lipase were greater than would have been predicted from alterations in the absolute rates of biosynthesis. In view of the rapid turnover of pancreatic enzymes under normal conditions, it seems probable that a markedly decreased secretory response to various stimuli leads to an increased content of some enzymes in the pancreas of the obese rat. Ciglitazone treatment, which decreases insulin resistance in obese animals and leads to normalization of glucose metabolism in their pancreatic tissue, restored the enzyme-synthesis rates towards normal, showing that the abnormalities of enzyme synthesis were linked to the insulin resistance rather than to the obese genotype itself. Lipid inclusion bodies were found in acinar cells of obese rats. These bodies have previously been described in acinar cells of starved animals, which, in common with the acinar tissue of the obese Zucker rat, have decreased glucose metabolism. PMID- 3325044 TI - The role of Ca2+ in the regulation of intramitochondrial energy production in heart. AB - In the heart and other mammalian tissues, there are three exclusively intramitochondrial dehydrogenases that occupy key sites in oxidative metabolism which can be activated by increases in Ca2+ in the range 0.1-10 microM. They are the pyruvate, NAD+-isocitrate and 2-oxoglutarate dehydrogenases. Activation of these enzymes can be demonstrated within intact mitochondria (incubated with Na+ and Mg2+) when extramitochondrial Ca2+ is raised within the expected physiological range (0.05-5 microM). Evidence is presented to suggest that the increase in cytoplasmic [Ca2+] caused by positive inotropic agents in the heart result in increases in intramitochondrial [Ca2+] and activation of the dehydrogenases and hence oxidative energy metabolism. Therefore it is proposed that the main function of the mitochondrial Ca2+-transport system is to regulate matrix rather than cytoplasmic Ca2+. In this way the stimulation of energy utilisation as contraction is enhanced is balanced by a parallel stimulation of ATP producing reactions. PMID- 3325043 TI - Expression of human glutathione S-transferase 2 in Escherichia coli. Immunological comparison with the basic glutathione S-transferases isoenzymes from human liver. AB - A plasmid, termed pTacGST2, which contains the complete coding sequence of a GST2 (glutathione S-transferase 2) subunit and permits the expression of the protein in Escherichia coli was constructed. The expressed protein had the same subunit Mr as the enzyme from normal human liver and retained its catalytic function with both GST and glutathione peroxidase activity. Antiserum raised against the bacterially synthesized protein cross-reacted with all the basic GST isoenzymes in human liver. The electrophoretic mobility in agarose of the bacterially expressed isoenzyme suggested that its pI is identical with that of the cationic isoenzyme from human liver previously termed GST2 type 1. The available evidence suggests that the three common cationic isoenzymes found in human liver are the products of two very similar gene loci. PMID- 3325042 TI - Purification and properties of L-mandelate dehydrogenase and comparison with other membrane-bound dehydrogenases from Acinetobacter calcoaceticus. AB - L-Mandelate dehydrogenase was purified from Acinetobacter calcoaceticus by Triton X-100 extraction from a 'wall + membrane' fraction, ion-exchange chromatography on DEAE-Sephacel, (NH4)2SO4 fractionation and gel filtration followed by further ion-exchange chromatography. The purified enzyme was partially characterized with respect to its subunit Mr (44,000), pH optimum (7.5), pI value (4.2), substrate specificity and susceptibility to various potential inhibitors including thiol blocking reagents. FMN was identified as the non-covalently bound cofactor. The properties of L-mandelate dehydrogenase are compared with those of D-mandelate dehydrogenase, D-lactate dehydrogenase and L-lactate dehydrogenase from A. calcoaceticus. PMID- 3325045 TI - Relevance of eicosanoids for biochemical regulation of cardiac rhythm disturbances. AB - The balance between the eicosanoids seems to be involved in the biochemical regulation of cardiac rhythm. Under several pathophysiological conditions thromboxane (TX) could be an important factor for the genesis of cardiac arrhythmias. Shifting the balance between the arrhythmogenic TX and the antiarrhythmic prostacyclin (PGI2) in favour of PGI2 by substances influencing the arachidonic acid cascade might by useful for the treatment of arrhythmias. PAF induced toxic arrhythmogenicity seems to be mediated by TX. Therefore the suppression of TX influence can antagonize these arrhythmias, too. PMID- 3325046 TI - Effects of computer controlled submaximal glucose utilization on myocardial energy potential and on survival time during acute strophantin intoxication in dogs. AB - We checked the effect of a 4 hourly computer controlled submaximal glucose utilization (CCSGU) of 12.01 +/- 1.19 mg/kg min under normoglycaemic conditions and of a simultaneous diminishing of myocardial NEFA supply on trigger mechanism of ventricular fibrillation during acute strophantin intoxication (4 micrograms/kg min) in 17 mongrel dogs. Dogs treated with CCSGU (protective group, n = 8) showed a nearly 30% (p less than 0.01) major survival time (47.6 +/- 3.6 min) before ventricular fibrillation occurred in comparison to a control group (33.1 +/- 3.7 min, n = 9). CCSGU induced a 90% higher left ventricular hydraulic work (5.18 +/- 0.57 Nm/g heart weight) during strophantin infusion compared to controls (2.75 +/- 0.47). No significant myocardial NEFA extraction was evident in the protective group. During CCSGU myocardial oxygen extraction was on a lower level in rest (15.8 +/- 1.0%, p less than 0.01) as well as during strophantin infusion (11.3 +/- 2.6%, p less than 0.01) compared to controls. In dogs treated with CCSGU nearly equal myocardial levels of HEP and lactate were found compared to controls in spite of a major survival time and higher left ventricular hydraulic work. A higher myocardial glycogen content was observed in the protective group (45.1 +/- 6.7 mumol/g w.w.) in comparison to controls (28.1 +/- 2.9, p less than 0.05). Our results prove that CCSGU using the device system GLUCON induces a shift in substrate utilization from NEFA to glucose, decreases myocardial oxygen extraction, increases myocardial glycogen content, enlarges heart work and protects against strophantin induced ventricular fibrillation. PMID- 3325047 TI - Influence of verapamil and its combination with glucose-insulin-potassium infusion on acute myocardial ischemia in dogs. AB - The influence of verapamil (V) and of V combined with glucose-insulin-potassium (VG) on ischemic injured myocardium was investigated in dogs after ligation of the left anterior descending coronary artery. Three hours after coronary artery ligation with VG application during the last two hours the left ventricular end diastolic pressure (LVEDP) and the pressure rate product were decreased in contrast to the behaviour after V infusion. Contents of ATP and creatine phosphate were preserved in equal extent by V and VG, but the lowest content in inorganic phosphate was found in ischemic and nonischemic left ventricular tissue after VG application. Thus, VG seems to enable the tissue to save more effective energy rich phosphates and to contribute to the economization of cardiac work by reduction of preload. PMID- 3325048 TI - Topological aspects of site-specific DNA-inversion. PMID- 3325049 TI - Clonal heterogeneity in fibroblast phenotype: implications for the control of epithelial-mesenchymal interactions. PMID- 3325050 TI - Kinetic isotope effects and 'metabolic switching' in cytochrome P450-catalyzed reactions. PMID- 3325051 TI - On G0 and cell cycle controls. PMID- 3325052 TI - The Xenopus animal pole blastomere. PMID- 3325053 TI - The Roche Institute of Molecular Biology. PMID- 3325054 TI - Permease on parade: application of site-directed mutagenesis to ion-gradient driven active transport. PMID- 3325055 TI - Regulation of chromosomal replication and transcription during early mammalian development. PMID- 3325056 TI - Eukaryotic DNA methylation and demethylation--sequence and strand specificity. PMID- 3325057 TI - mRNA caps--old and newer hats. PMID- 3325058 TI - A short history of the Roche Institute of Molecular Biology. PMID- 3325059 TI - Tissue specificities of protease A-like esteroprotease in male mice. AB - An esteroprotease hydrolyzing p-tosyl-L-arginine methyl ester (TAME) has been purified to homogeneity from male mice submandibular glands by the ammonium sulphate precipitation, Sephadex gel chromatography and DEAE-cellulose chromatography. The enzyme was shown as a single chain acidic protein (pI = 5.7) with the molecular weight of 27.5 K and evidence was obtained to reveal that it was similar to protease A. Using this enzyme as antigen we prepared anti-TAMEase antibody. The immunoblotting studies on tissue specificity using 20 different tissues from male mice revealed that cross-reactivities with anti-TAMEase antibody were observed in the crude extract from the sublingual gland, parotid gland and pancreas. The species specificity studies with the submandibular glands of 7 different species indicated that only the crude extract from rat submandibular glands reacted against anti-TAMEase antibody but it exerted a low TAMEase activity. PMID- 3325061 TI - DNA bound RNA polymerase activity of the yeast nuclei. AB - A preparation of nuclei from yeast cells is shown to be capable of autodigesting its chromatin in the presence of a series of magnesium containing buffers having different concentrations of potassium. The 'digests' or 'extracts' prepared in this manner contain an active transcription complex which can transcribe endogenous as well as exogenous DNA template. The effects of heparin and actinomycin D on the in vitro transcription by these complexes confirm the presence of RNA polymerase in DNA bound form. Further purification of this transcription complex is attempted by sucrose density gradient centrifugation. Circular dichroic measurements show that the nuclear DNA exists in compact state in the extracts. PMID- 3325060 TI - Hepatic glycoprotein synthesis in streptozotocin diabetic rats. AB - In vitro incorporation of 3H-mannose into dolichol phosphate mannose, dolichol pyrophosphate oligosaccharides, and secretory and membrane glycoproteins was investigated in liver slices from streptozotocin diabetic rats. In addition, 14C leucine incorporation into glycoproteins was studied. 3H-mannose incorporation was significantly less in secretory glycoproteins from diabetic rat liver slices than from control tissues, but 14C-leucine incorporation in these proteins was similar in both groups. Dolichol-phosphate mannose and dolichol-phosphate oligosaccharide synthesis were significantly down-regulated in diabetes. When incubated with insulin, mannosylation of secretory proteins, dolichol-phosphate mannose and dolichol-phosphate oligosaccharides reached control levels in three hours. Dolichol-phosphate mannosyltransferase activity was significantly less in diabetes, while in the presence of insulin, the enzyme activity reached control levels in three hours. These results indicate that key intermediates in glycoprotein biosynthesis are regulated by insulin. PMID- 3325062 TI - Characterization of the substrate-binding sites of the mitochondrial nicotinamide nucleotide transhydrogenase. AB - The mitochondrial energy-linked nicotinamide nucleotide transhydrogenase (TH) is modified and inhibited by p-fluorosulfonylbenzoyl-5'-adenosine (FSBA). The modification appears to occur at the NAD(H)-binding site when TH alone or TH in the presence of NADPH is incubated with FSBA. However, when this site is protected by NADH, then FSBA inhibits TH more slowly and modifies a different, though specific, site. This second site could be the NADP(H)-binding site. Using [3H]FSBA in the presence of NADPH, the NAD(H)-binding site was modified, and a single tryptic peptide carrying the label was isolated and sequenced. The amino acid sequence of this peptide was Glu-Ser-Gly-Glu-Gly-Gln-Gly-Gly-Tyr*-Ala-Lys. The modified residue was Tyr. The labeled peptide isolated after incubating TH with [3H]FSBA in the presence of NADH could not be completely purified. However, amino acid analysis and partial sequencing made it possible to identify this segment on the amino acid sequence of bovine TH as derived from its cDNA by Yamaguchi et al. (private communication). PMID- 3325063 TI - The precursor of acid alpha-glucosidase is synthesized as a membrane-bound enzyme. AB - A pulse-chase study in human skin fibroblasts showed that a 110 kDa precursor of acid alpha-glucosidase was synthesized as a membrane-bound protein, which was solubilized in vitro not by mannose 6-phosphate or 1M KCl but by Triton X-100 or trypsin. This 110 kDa precursor form bound to the membrane was detected in control fibroblasts treated with tunicamycin and in I-cell disease fibroblasts as well. The precursors in human placenta were found also in the membrane fraction. It was concluded that the newly synthesized acid alpha-glucosidase precursor is located on the surface of the membrane, and the phosphomannosyl receptor does not participate in the enzyme-membrane binding. PMID- 3325064 TI - [Interaction of s4U8 region of tRNA Phe with tRNA-(adenine-1-)-methyltransferase from Thermus thermophilus]. AB - Photoaffinity labelling of tRNA (adenine-1-)-methyltransferase with an E. coli tRNA(Phe) derivative bearing 4-azidophenylmercuro group attached to s4U residue as well as direct photocross-linking of the native tRNA(Phe) with the enzyme via s4U residue has been studied. Both techniques labelling gave similar results, leading to covalent attachment of tRNA(Phe) to the enzyme within a specific complex. The data obtained indicate unambigously that s4U residue contacts with tRNA (adenine-1-)-methyltransferase within the corresponding specific complex. PMID- 3325066 TI - Lack of effectiveness of ofloxacin against experimental syphilis in rabbits. AB - Ofloxacin, a new pyridone-carboxylic acid derivative, was evaluated in experimental syphilis in rabbits in comparison with penicillin G. Experimental syphilis was established by intradermal injection of Treponema pallidum subsp. pallidum Nichols. Ten days after infection, the dermal lesions were characterized by syphilitic papula accompanied with central necrosis. These animals were subsequently treated either with ofloxacin twice a day at an oral dose of 10 mg/kg or with penicillin G once a day at an intramuscular dose of 10,000 U/kg for 21 consecutive days. In penicillin G-treated animals, the dermal lesions became smaller as early as day 3 of treatment and almost disappeared during the therapy. In marked contrast to remarkable efficacy of penicillin G was further development of the lesions in ofloxacin-treated animals, showing no difference in pathological manifestations as compared to untreated animals. The results of nontreponemal serologic test correlated well with the response of animals to treatment. PMID- 3325065 TI - Connective tissue activation. XXXI. Identification of two molecular forms of a human mesenchymal cell-derived growth factor, connective tissue activating peptide-V. AB - We previously identified, in normal urine, a growth factor that stimulated monolayer cultures of human synovial, cartilage, and dermal fibroblasts to synthesize incremental amounts of hyaluronic acid, proteoglycans, and DNA. An isolation procedure guided by bioassays and immunologic methods disclosed 2 anionic bioactive polypeptides with Mr of 28,000 and 16,000, respectively, as judged by single bands with sodium dodecyl sulfate-polyacrylamide gel electrophoresis in reduced and nonreduced samples. Rabbit antibodies raised against each purified protein were shown to react, on immunodiffusion and Western blot, with both antigens. Immunohistochemical and immunobinding studies detected the protein in normal human synovial, dermal, and cartilage fibroblasts and in human saphenous vein endothelial cells. The mesenchymal cell-derived growth factor is now designated connective tissue activating peptide-V (CTAP-V). Monospecific polyclonal anti-CTAP-V antibodies were used in a radial immunodiffusion assay for quantitative determination of the antigen in biologic fluids. In normal human plasma the concentration of CTAP-V was below the limit of detection. The CTAP-V concentration in normal urine was 4.5 +/- 2.0 micrograms/ml, calculated from measurements of 5-18-fold concentrated samples. Joint fluid from patients with rheumatic diseases and normal renal function had CTAP-V levels similar to those found in plasma; 2-15-fold increases were detected in plasma and joint fluid of patients with chronic renal failure. Immunodiffusion or dot-blot analysis revealed a CTAP-V-like material in the plasma or serum of 10 mammalian species. It was not detectable in 2 avian species. PMID- 3325067 TI - [Polyps and glandular polyposis of the fundus. Study of 20 cases and review of the literature]. AB - An histological and histochemical study has been performed in 20 cases of fundic gland polyps. In five cases, polyps were numerous and associated, in two cases, with a familial adenomatosis coli. The histological, histochemical characteristics and the study of semi-serial sections suggest that fundic gland polyp is a focal distension of the fundic tube without evidence of an hamartomatous neither a neoplastic origin. Because of a possible association with a familial colonic polyposis, an endoscopical investigation is usefull, specially in fundic gland polyposis. PMID- 3325068 TI - [Fibro-inflammatory polyp with eosinophilic infiltration. Apropos of 3 cases of gastric polyps]. AB - We report three cases of inflammatory fibroid polyp of the stomach (Helwig's pseudo-tumour) and record 127 patients in the literature. The anatomo-clinical features of such a disease are analysed and the larger outline of eosinophilic infiltrations of the gastro intestinal tract are described. Most of the authors class the gastric nodular eosinophilic granuloma as the Helwig's pseudo-tumour, but they are not so unanimous for the exact relationship between inflammatory fibroid polyp and the eosinophilic gastroenteritis. For Helwig, they are two distinct conditions, but for others, they belong to the same anatomo-clinical entity, with a broad diversity of morphological features. PMID- 3325069 TI - [Nemaline myopathy. General review apropos of 3 cases]. AB - Three cases of nemaline myopathy are reported. The first one was characterized by delayed motor milestones, hypotonia and proximal weakness in a 2-year-old girld. The second case was diagnosed at 19 in a boy who suffered from a severe scoliosis without any neurological sign. The third patient was a 31 year-old man who had a progressive muscular weakness of limb girdles. Muscle biopsy revealed rods in muscle fibers with Gomori trichrome staining in two cases, and by electron microscopy in one case only. Variations of fiber calibration, fiber I predominance and a myofibrillar disorganization were seen in two cases. Clinical, histopathological and physiopathological of nemaline myopathy are discussed. PMID- 3325071 TI - [On the article by Korbi, Kapanci and Widgren, "Malignant paraganglioma of the duodenum"]. PMID- 3325070 TI - [Microphotometric system of analysis with automatic scanning and immunodetection: application to tissue sections (breast, endometrium, uterine cervix, ovary]. AB - In the present study the immunodetection of various markers in a large series of tissue samples have been analysed through the computerized system of image analysis referred to as SAMBA 200. The immunodetection of estrogen and progesterone receptors, Laminin and type IV collagen, Ki 67, keratin, papilloma virus have been performed in frozen sections or in imprints and fine needle aspirates from tumorous and non tumorous disorders of human breast, endometrium, cervix and ovaries. Staining procedures varied with the type of the marker studied (PAP, ABC-P, ABC-GO, APAAP). The results obtained by the multiparametric SAMBA analysis were accurate, reproducible and reliable. Therefore, the SAMBA analysis providing a standardized and automatic analysis of immunodetection performed in tissue sections can be routinely used in pathology laboratories particularly for the prognostic evaluation and for the prediction of hormonotherapy and chemotherapy response of patients with solid malignant disorders. PMID- 3325072 TI - Improved nuclear contour indices for lymphoid morphometry. AB - The morphometric analysis of benign and neoplastic lymphoid proliferations relies heavily on nuclear shape factors to identify clefted, cerebriform or convoluted nuclei. Most studies employ the size-independent nuclear contour index (NCI = perimeter/square root area) or the closely related (nuclear) form factor to evaluate the degree of nuclear irregularity. These indices, however, cannot distinguish a truly irregular shape from a perfectly smooth elliptical one. A variation of the standard NCI is therefore proposed in which the NCI of the ellipse (NCIe) that best approximates the nuclear shape is determined to indicate the degree of nuclear elongation or ellipticity and the separate NCI of the nuclear irregularity (NCIni) is determined to indicate the true irregularity of the nuclear perimeter, independent of nuclear elongation. These two new shape factors were tested on a series of shapes and on mantle and follicular-center cells present in 3-micron plastic-embedded sections from three tonsils with reactive lymphoid hyperplasia. Whereas the standard NCI increased with increasing ellipticity or nuclear irregularity, the NCIe increased only with increasing ellipticity and NCIni with increasing nuclear irregularity. Mantle cell and, to a greater extent, follicular-center-cell nuclei showed mean NCIe and NCIni greater than what would be expected from a perfectly round nucleus. These nuclei, therefore, were both more elliptical and more irregular in outline than a perfect circle. The NCIe and NCIni were shown to vary independently in both mantle and follicular-center cells. These new and relatively simple indices should lead to a more accurate morphometric description of lymphoid cells. PMID- 3325073 TI - [Prevalence of viral hepatitis B markers in a sample of students at the School of Medicine and Surgery, University of Brescia]. AB - Seroepidemiologic study on hepatitis B virus markers in a group of students in Medicine at the University of Brescia. The prevalence of hepatitis B virus (HBV) markers was studied in a group of 633 students in Medicine at the University of Brescia. HBsAg was detected in 16 (2.5%) students; anti-HBs and anti-HBc in 73 (11.5%); anti-HBs alone in 4 (0.6%); anti-HBc alone in 9 (1.4%). On the whole 102 (16.1%) students were reactive for one HBV marker at least. Significant differences in frequency of HBV markers were found according to age and to personal and familiar history of viral hepatitis; the prevalence of the markers was not associated with sex, year in school, hospital clinical training, blood transfusions and presence of health-care workers in the family. In this seroepidemiologic study the risk of contracting hepatitis B appears not higher in medical students than in other university students and in general population of the same age, sex and residence area. The results of the investigation suggest that medical students are appropriate candidates for hepatitis B vaccine at the beginning of their post-graduate medical profession. PMID- 3325074 TI - [Epidemiological aspects of imported malaria 1976-1985]. AB - The comparative analysis of the cases of imported malaria in Lombardy and in Italy during the ten-years period 1976-1985 shows that the prevalent factors of risk are, in both case-lists, the young age, the work motivated travelling and the stay in endemic areas of tropical Africa, where P. falciparum is greatly prevalent. Interesting outcomes of comparison of the two consecutive five-years periods 1976-1980 and 1981-1985 are discussed. As far as the african provenience (decreased) and the work motivated travelling (increased) are concerned, the two case lists are consistent and agree, yet P. falciparum malaria cases are decreased in Lombardy only. The increasing habit of chloroquine chemoprophylaxis in Lombardy, the persistant sensitivity of P. vivax to this drug and the widespread extent of chloroquine-resistant P. falciparum strains in Africa are to be taken into account. PMID- 3325075 TI - Asymptomatic parasitic infections in renal transplant recipients and in haemodialysis patients. AB - One hundred and sixty-seven clinically asymptomatic renal transplant recipients and 119 patients on chronic haemodialysis were studied for the presence of intestinal parasites and for the prevalence of anti-Toxoplasma gondii antibodies. Intestinal parasitic infections were more frequently found in transplant recipients than in haemodialysis patients and in controls. Among transplant recipients, the prevalence rate of T. gondii antibodies at high titres was significantly increased, but in these subjects the positivity rate of specific IgM assays was reduced. This seems to indicate a greater occurrence of asymptomatic reactivated infections. Our findings suggest that parasitologic surveys of immunosuppressed patients should be periodically performed also in temperate climates, in order to prevent the possibility of disseminated infections. PMID- 3325076 TI - [Antibody response in cultures of lymphocytes from patients with Hodgkin's lymphoma: role of monocytes]. AB - In the present study we investigated the role of monocytes and of their soluble products (prostaglandins and hydrogen peroxide) in the modulation of the immune response in 50 untreated patients with Hodgkin's disease (HD) compared with a group of healthy donors. The primary response in vitro has been studied with the method of haemolytic colonies in soft agar. A defective in vitro antibody production has been observed in HD patients. Both Indomethacin addition (10(-6) M, final concentration) and depletion of plastic adherent cells, slightly increased the number of haemolytic areas in cultures from HD patients as compared with healthy donors. Similarly, the addition of catalase (8000 U/ml) which destroys H2O2, that is the main mediator of monocytes suppressor activity in normal subjects, did not restore the response of peripheral blood mononuclear cells (PBMC) from HD patients. These results suggest that monocytic cells play a minor role, if any, in the depression of the immune response in HD patients. PMID- 3325077 TI - Rapid assay of poly(ADP-ribose) glycohydrolase. AB - We have developed a rapid, highly reproducible assay to determine poly(ADP ribose) glycohydrolase activity which measures directly the appearance of the reaction product. We also analysed the majority of different techniques which are used to determine poly(ADP-ribose) glycohydrolase activity and found that the apparent activity can vary extensively depending on the method used. Thin-layer chromatography using PEI-F-cellulose was the only method which evaluated directly the specific release of ADP-ribose; by comparison with this method, the other procedures gave an over- or under-estimation of 2- to 10-fold of the enzymatic activity. A rapid method of affinity chromatography has also been developed to synthesize and purify in high yield poly(ADP-ribose) (35% conversion of 1 mM NAD to poly(ADP-ribose)). PMID- 3325078 TI - Limb regeneration in vertebrates: regulatory factors. AB - Various regulatory factors are required in epimorphic regeneration of an adult newt limb. These factors (namely, amputational injury, the wound and apical epithelium, nerves (mitogenic agents), hormones (the hormonal milieu), bioelectric fields, probably the immune system, and possibly cyclic nucleotides and heretofore unknown regulators) act in concert and contribute to the developing microenvironment of the regenerate in support of normal regrowth and differentiation. PMID- 3325079 TI - Cell cycle controls and the role of nerves and the regenerate epithelium in urodele forelimb regeneration: possible modifications of basic concepts. AB - Data from pulse and continuous labeling with [3H]thymidine and from studies with monoclonal antibody WE3 have led to the modification of existing models and established concepts pertinent to understanding limb regeneration. Not all cells of the adult newt blastema are randomly distributed and actively progressing through the cell cycle. Instead, many cells are in a position that we have designated transient quiescence (TQ) and are not actively cycling. We postulate that cells regularly leave the TQ population and enter the actively cycling population and vice versa. The size of the TQ population may be at least partly determined by the quantity of limb innervation. Larval Ambystoma may have only a small or nonexisting TQ, thus accounting for their rapid rate of regeneration. Examination of reactivity of monoclonal antibody WE3 suggests that the early wound epithelium, which is derived from skin epidermis, is later replaced by cells from skin glands concomitant with blastema formation. WE3 provides a useful tool to further investigate the regenerate epithelium. PMID- 3325080 TI - Use of retinoids to analyze the cellular basis of positional memory in regenerating amphibian limbs. AB - Cells of the amphibian limb regeneration blastema inherit memories of their level of origin (positional memory) along the limb axes. These memories serve as boundaries of what is to be regenerated, thus preventing regeneration of any but the missing structures. Because of its importance in determining the boundaries of regenerate pattern, it is essential to understand the cellular and molecular basis of positional memory. One approach to this problem is to look for position related differences in a cell or molecular property along a limb axis and then show, using an agent that modifies regenerate pattern, that the cell or molecular property and the pattern are coordinately modified. We have done this using retinoic acid (RA) as a pattern-modifying agent and an in vivo assay that detects position-related differences in a cell recognition-affinity property along the proximodistal (PD) axis of the regenerating axolotl limb. RA proximalizes positional memory in the PD axis, posteriorizes it in the anteroposterior axis, and ventralizes it in the dorsoventral axis. The level-specific PD cell recognition-affinity property is proximalized by RA, indicating that this property and positional memory are causally related. The effects of RA on positional memory may be mediated through a cellular RA-binding protein (CRABP), since the concentration of unbound (apo) CRABP molecules is highest during early stages of regeneration when the proximalizing effects of RA are greatest. PMID- 3325081 TI - Indications for penetrating keratoplasty: a clinicopathological review of 511 corneal specimens. AB - During the four-and-a-half year period from January 1982 to June 1986, 511 penetrating keratoplasty specimens were submitted to the Pathology Department of The Royal Victorian Eye and Ear Hospital. Seventy per cent were from patients of the RVEEH and the remainder were submitted from outside the Hospital. The cases were classified both clinically and pathologically. The most frequent diagnosis was keratoconus, followed by scarring, regrafts, bullous keratopathy, acute or chronic ulceration, corneal dystrophies and a small miscellaneous group. Post herpetic scarring was the most common cause of scarring. Bullous keratopathy was usually aphakic in origin in 1982, but after 1983 pseudophakic bullous keratopathy (PBK) was the most common cause of bullous keratopathy. Acute ulceration was usually bacterial in origin, not infrequently with hypopyon. PMID- 3325082 TI - First report of the Australian Corneal Graft Registry. AB - In the Australian Corneal Graft Registry's first 18 months of operation, May 1985 to November 1986, data supplied by 53 surgeons relating to 322 graft recipients have been entered and analysed with respect to: the most common presenting diseases (primarily keratoconus, bullous keratopathy and corneal opacities), risk factors (especially prior sensitisation to HLA antigens, corneal vascularisation, past or present anterior segment inflammation and history of raised intraocular pressure [IOP]), donor and recipient sex, cause of donor death, storage procedures for donor eyes, operative procedures accompanying the grafts themselves, and preliminary indications of overall graft survival by actuarial analysis. It is hoped that the establishment of this Registry will not only reinforce the use of actuarial graft survival analysis as the method of choice for transplantation surgeons wishing to monitor the survival of their patients and grafts, but will also provide a useful service for the Australian ophthalmic community in general. PMID- 3325083 TI - Computer-aided area measurement of ocular images. AB - Using a combination of computer-aided measurement techniques and fundus camera images, the area of regions of interest on the fundus can be measured. If these area measurements are corrected for the magnification effects of the patient's visual system, and the fundus camera optics, an estimate of the true anatomical size of the measured object can be determined in physical units. While the results of measuring models indicate a maximum error of 6% for the system, the results of clinical trials demonstrate an average error of 10% for well-defined areas of interest, with increasing error of up to 30% for poorly defined areas of interest. PMID- 3325084 TI - Computer-aided volume measurement of choroidal melanomas. AB - Using a combination of conventional B-scan ultrasonography, standard video techniques, computer image digitization and area analysis, it is possible to measure the volume of choroidal melanomas by area calculation of successive ultrasound image slices, allowing the monitoring of such tumors. The design of a combined water-bath and linear tracking B-scan transducer is presented, together with a description of the instrumentation and computer software required. The results of volume measurements performed upon eye models demonstrated that melanomas of volume greater than 100 mm3 could be measured with an average error of 6%. The problems associated with linear calibration of the system from scan head to analysed image, resolution of the digitised image, reproducibility of the measurements, sources of error and assumptions made in formulating the measurement procedure are discussed. PMID- 3325085 TI - Melanin: blackguard or red herring? Another look at chloroquine retinopathy. PMID- 3325086 TI - Influence of specimen treatment on nonreactive HTLV-III sera. AB - We investigated effects of specimen treatment on HTLV-III antibody assay results. Freezing and thawing specimens 10 times did not increase specimen mean absorbance (A) values measured by the Abbott immunoenzymometric assay (IEMA). Heating blood donor serum specimens at 56 degrees C for at least 10 min inactivates virus, but converted 7.1% of nonreactive specimens to positive when measured by this IEMA. Also heating at 56 degrees C for 30 min increased A values of most specimens; however, the conversion to positive within assay ranged from 0 to 75%, with a mean of 17%. When 56 nonreactive patient specimens were heated, 55% became Abbott IEMA reactive, although ENI IEMA values did not increase and Western blot results remained nonreactive. Binding of immunoglobulins G and A to Abbott IEMA beads did not cause this conversion after heat treatment. We postulate that heating specimens causes alteration of some serum matrices and introduces nonspecific binding to assay bead antigen or antibody reagents. We recommend that for the Abbott IEMA, specimens may be stored frozen, and must not be heated to avoid altered reactivity. PMID- 3325087 TI - [Two cases of intracranial fibromuscular dysplasia whose repeated angiography disclosed progression of the lesion]. AB - Fibromuscular dysplasia (FMD) is well known owing to the characteristic angiographical finding of a "string of beads" appearance, but intracranial involvement with this disease is extremely rare. Moreover, to our knowledge, only seven cases that had repeated angiograms disclosed progression of FMD lesion in the literature. Such cases of intracranial FMD which showed progression in the follow-up angiography are reported. Case 1: A 8-year-old boy was referred to our hospital because of aphasia and right hemiplegia following right hemiconvulsion. Left carotid angiography on the 7th day from the onset revealed a "string of beads" appearance involving the left middle cerebral artery from M1 to M2 portion. He was treated with low molecular dextran, urokinase and steroid. After these drugs were administered, his speech was normalized. A repeat left angiogram performed two months later disclosed definite increase in the degree of stenosis associated with FMD. Perivascular sympathectomy around common and internal carotid artery and superior cervical ganglionectomy on the left side carried out on the 70th day from the onset. Postoperative left carotid angiogram showed improvement of the stenosis markedly, and the motor disturbance was improved gradually. Case 2: A 34-year-old woman presented with head dullness and disorientation suddenly. Left carotid angiogram on the third day from the onset showed a "string of beads" appearance from C1 to M1 portion. Follow-up angiography three days later revealed some progression of the stenosis. Furthermore a repeat left angiogram disclosed occlusion of left internal carotid artery at the C2 portion. Left STA-MCA bypass surgery was performed on the 61st day from the onset.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325088 TI - [Clinical significance of beta 2-microglobulin and carcinoembryonic antigen in intracranial tumors]. AB - Beta 2-microglobulin (beta 2-MG) levels were determined in serum, cerebrospinal fluid (CSF), and tumor cyst fluid obtained from patients with a variety of intracranial tumors. In addition, a simultaneous determination of the carcinoembryonic antigen (CEA) was carried out in some patients. The beta 2-MG levels were elevated in 11/101 intracranial tumors, including glioma (4/34), non glial tumors (1/18), malignant lymphoma (2/18), and metastatic brain tumors (4/31). There were no significant differences in the beta 2-MG levels of serum among the different patient groups. On the other hand, the beta 2-MG levels in CSF were significantly higher in patients with malignant lymphoma and metastatic brain tumors than in those with glioma and non-glial tumors. Fifteen (83.3%) of 18 patients with malignant lymphoma and 6(25.0%) of 24 patients with metastatic brain tumors showed increased the levels of beta 2-MG in CSF. The beta 2-MG levels in the tumor cyst fluid of 11 intracranial tumors exceeded normal serum levels in all but two patients. When the CEA levels in the serum and CSF were measured simultaneously, meaningful differences between malignant lymphoma and metastatic brain tumors were clearly observed. The highest incidence and highest levels of the CEA in serum and CSF were only noted in patients with metastatic brain tumors. Conversely, the serum CEA was slightly raised in 11.8% of malignant lymphoma and the levels of CEA in CSF were within normal range in all these patients. Serial determination of CSF beta 2-MG in patients with malignant lymphoma correlated well with their clinical findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325089 TI - [Epileptogenic properties of quisqualic acid: microinjection into the unilateral amygdala in cats]. AB - The present studies demonstrated that the microinjection of quisqualic acid (QA) into unilateral amygdala in chronically implanted cats resulted in various types of limbic seizures in accordance with injected doses. The epileptogenic potency of QA in the induction of epileptic seizures was lower then that of kainic acid (KA), which has also been demonstrated in our previous studies. Electroencephalographic changes and clinical manifestations of QA-induced epilepsy were less prominent as compared with those of KA-induced epilepsy. Five micrograms of QA resulted in pure amygdaloid seizures. The moderate dose administration of QA (15 micrograms) was suitable to observe limbic status. Both doses of QA elicited similar characteristic epileptic patterns on EEG, which was quite distinguishable from those of KA. In pathological study, mild degeneration of hippocampal pyramidal cell layer was observed in the cases injected 15 micrograms of QA. These electro-clinical and pathological features are interesting in similarities to those of human complex partial seizures, mesial temporal sclerosis. In conclusion, the strict dose dependency of QA in the production of limbic seizures is a valid advantage for an experimental model of a complex partial epilepsy in man. PMID- 3325091 TI - Development of optimal infusion regimens for epoprostenol using radio labelled platelet uptake over atherosclerotic lesions in man. AB - 1. Epoprostenol (prostacyclin, PGI2) has been evaluated in clinical trials in peripheral vascular disease and other conditions chiefly on the basis of its platelet inhibitory properties. These therapeutic evaluations have proceeded in the absence of evidence as to the optimum infusion regimen for epoprostenol and the choice of schedules of administration has been arbitrary. We have tried to establish an optimum infusion regimen in patients with peripheral vascular disease in terms of maximal inhibition of platelet deposition on atherosclerotic lesions in vivo together with maximal inhibition of platelet aggregation ex vivo. 2. One hundred and twenty three patients with atherosclerotic peripheral vascular disease and increased platelet uptake at atherosclerotic sites were selected. Epoprostenol was administered at a fixed dose of 5 mg kg-1 min-1 for 0.5-24 h daily for 3-7 days. 3. Infusion of epoprostenol for 6 h daily for up to 5 days caused maximum decrease in platelet uptake without tachyphylaxis and without loss of the inhibitory effect of epoprostenol on platelet aggregation responses. Longer daily infusion periods were associated with progressive loss of the anti aggregatory effect of epoprostenol without any greater decrease in platelet uptake. Shorter daily infusion periods produced smaller decreases in platelet uptake. PMID- 3325090 TI - Acute and chronic ketanserin in essential hypertension: antihypertensive mechanisms and pharmacokinetics. AB - 1. In nine patients with essential hypertension, following single and multiple doses of ketanserin, assessments were made of blood pressure and heart rate, QT interval, and pressor responses to phenylephrine and angiotensin II. 2. Significant reductions in blood pressure occurred for 6 h after the first dose, on average 23/14 mm Hg supine, and there was a comparable antihypertensive effect after 1 month's treatment. 3. There were small but significant rightward shifts (1.5 to 2-fold) in the phenylephrine pressor-response curves but no changes in the responsiveness to angiotensin II. 4. The QT interval (QTc) was significantly increased after 1 month's treatment: at 1 h after dosing 334 +/- 32 ms after 1 month of ketanserin compared with 302 +/- 31 ms after placebo. 5. The elimination half-life and AUC for ketanserin were both significantly increased at steady state compared with the first dose: respectively 13.4 vs 4.3 h for half-life and 830 vs 437 ng ml-1 h for AUC. 6. Ketanserin had no significant effects on baroreflex function, plasma renin activity, aldosterone, catecholamines and 24 h urinary excretion. PMID- 3325092 TI - Parkinson's disease in the elderly: response to and optimal spacing of night time dosing with levodopa. AB - 1. Insomnia is an even more frequent complaint in elderly patients with Parkinson's disease than might be expected from the effect of age alone on sleep. 2. A double-blind, placebo-controlled trial in eleven patients with Parkinson's disease of mean (s.d.) age 80(5) years, showed that nocturnal dosing with levodopa produced a clinically significant improvement in sleep both as assessed subjectively and by measurement of number of spontaneous moves in bed. 3. Despite the long interval between tablet administration and morning assessment, walking time was faster on mornings following active treatment. PMID- 3325093 TI - Human monoclonal antibodies and monoclonal antibody multispecificity. AB - The majority of human anti-tumour monoclonal antibodies (Mabs) isolated to date have been disappointing. Firstly, they react or cross react with intracellular cytoskeletal proteins or nuclear antigens and therefore are of limited value as blood borne agents. They are also generally of the IgM isotype and show relatively low intrinsic affinity for the primary epitope. Secondly, such Mabs can be generated from normal, non tumour bearing subjects at a frequency comparable to their production from tumour patients. This latter observation is true also for common autoantigens such as DNA and IgG since Mabs to these can also be generated from normal subjects in addition to autoimmune individuals. This article rationalises these observations in the context of the requirement for clinical use for human Mabs. It discusses the evidence that there is a potentially useful B cell response to be immortalised, and examines the consequences of the newly recognised phenomenon of monoclonal antibody multispecificity both on the methodology of their generation and on their subsequent use as imaging and therapeutic tools. PMID- 3325094 TI - A critical appraisal of the immunohistochemical detection of the c-myc oncogene product in colorectal cancer. AB - Expression of c-myc was studied immunohistochemically in 100 colorectal carcinomas, using a monoclonal antibody, Myc 1-6E10, which is purported to recognize the oncoprotein (p62c-myc) in paraffin-embedded material. In normal epithelium, maturing crypt cells and terminally differentiated surface cells were positive, and proliferating basal crypt cells negative. All carcinomas stained positively, but intensity was independent of histological differentiation, Dukes' stage, DNA ploidy and survival. Staining was predominantly cytoplasmic despite the suspected nuclear location of p62c-myc and there was considerable staining of fibroblasts. When staining was compared in frozen and paraffin-embedded sections fixed in different ways, different patterns were observed. Acetone-fixed frozen sections exhibited weak nuclear and cytoplasmic staining or were negative. In formol-saline fixed frozen sections, there was stronger predominantly nuclear staining. In paraffin-embedded sections staining was predominantly cytoplasmic. This study suggests that c-myc expression is enhanced in the majority of colorectal carcinomas and although independent of clinical behaviour, may be a common event in malignant transformation. However, since staining is affected by fixation and processing, data obtained using Myc 1-6E10 on routinely processed specimens should be interpreted with caution. PMID- 3325096 TI - The development of dental education in the United Kingdom with special reference to orthodontics. AB - The history of the developments in Dental Education in the British Isles is discussed starting in the middle of the eighteenth century with the work by John Hunter, and many to the present day. Stress is laid in the preservation of these improvements in both undergraduate and postgraduate education and the needs for close contact with bodies outside of orthodontics. PMID- 3325095 TI - Evaluation of p62c-myc in benign and malignant gastric epithelia. PMID- 3325097 TI - Methods of attachment for palatal arches: an evaluation. AB - Orthodontic appliances attached to the palatal surfaces of molar bands are commonly used to produce, or is an aid to, active tooth movement. The present paper describes a number of the systems available for achieving this attachment and investigates their advantages and disadvantages in clinical practice. PMID- 3325098 TI - An interview with Professor Mills. PMID- 3325099 TI - Rebonding attachments to surgically exposed teeth. PMID- 3325100 TI - [Fiber-reinforced bioactive glass: a possible dental implant material]. PMID- 3325101 TI - Legal issues in perinatal care. PMID- 3325102 TI - An interdisciplinary team approach to diagnostic ultrasound. PMID- 3325103 TI - Chorionic villus sampling: implementing a new genetic diagnostic tool. PMID- 3325104 TI - Liability of treaters for injuries to others: erosion of three immunities. AB - For years treaters of mental patients who harmed other persons were largely protected by three doctrines: the common law rule of nonresponsibility, sovereign immunity, and the "honest error" rule. The present paper examines the erosion of these immunities that has occurred over the last 30 years. As the strength and breadth of these protections have lessened, claims of negligence have expanded. Failure to properly diagnose includes failure to foresee violent acts. Failure to properly treat includes failure to restrain a violent patient. The recently asserted failure to protect others is not necessarily based on failure to diagnose or to treat, or, for that matter, on medical malpractice law. PMID- 3325105 TI - Military combat, posttraumatic stress disorder, and criminal behavior in Vietnam veterans. AB - Although data are inconclusive, popular perception has linked military combat, posttraumatic stress disorder (PTSD), and criminal behavior. This paper discusses the multifactorial elements of this association that include both conscious and unconscious parameters of psychologic functioning. Testimony on combat-related PTSD has been presented in the courtroom to support veterans' claims of not guilty by reason of insanity (NGRI) and diminished capacity and for consideration during judicial sentencing. Because there is a known connection between the degree of combat involvement and PTSD, verification through collateral sources of the veteran's report of combat experiences is an important component of forensic assessment. The DSM-III-defined diagnosis of PTSD and the presence of a dissociative state have particular relevance in NGRI determinations. In other aspects of the judicial process demonstration of the absolute presence or absence of PTSD is often irrelevant and should be replaced by efforts to establish plausible links between provable combat experiences and the circumstances of the crime. PMID- 3325107 TI - The status of dentistry at the time of Frederick the Great: 1712-1786. PMID- 3325108 TI - The true discoverer of the dental air turbine handpiece, Sir John Walsh of New Zealand. PMID- 3325106 TI - [Activated oncogenes in human tumors]. AB - ras oncogenes are cellular genes altered by point mutation in 10 to 30% of human tumors. Under this mutated form they play a role in the malignant process, probably in association with other oncogenes. The different ras genes identified in human cancers, the point mutations that activate the ras genes and the properties of the ras proteins are described. PMID- 3325109 TI - Dentistry in the writings of Albucasis during the Golden Age of Arabian medicine. PMID- 3325110 TI - The American Academy of the History of Dentistry: recollections of a founder. PMID- 3325111 TI - A case of prosthetic dentistry in ancient Egypt. PMID- 3325112 TI - Oddments in dental history: a warning about unskilled extractionists in 19th century England. PMID- 3325113 TI - Choicest "receipts" from "The Complete Servant-maid", London, 1685. PMID- 3325114 TI - On the occasion of the 150th anniversary of the birth of G.V. Black. PMID- 3325115 TI - Dentistry in folk art XXV: The Good Parisians. Honore Victorin Daumier (1808 1879)--French. The Good Parisians--no. 4 lithograph probably published in "Le Charivari", circa 1852. PMID- 3325116 TI - American Academy of the History of Dentistry. Roster of members as of July 15, 1987. PMID- 3325117 TI - Reflections on a dental centennial: 100 years of Meharry's Dental School. PMID- 3325118 TI - The struggle for fluoridation: a personal and historical perspective. PMID- 3325119 TI - Effects of cold on old people. AB - Increased morbidity and mortality from cardiovascular and respiratory disease in the elderly is strongly associated with cold winters in Britain. Though there is often impairment of thermoregulation in old people, deaths from hypothermia are proportionally small. Recent physiological investigations on the effects of cold in the elderly may help to explain the causes of excess winter deaths. PMID- 3325120 TI - Meningococcal meningitis. AB - Meningococci continue to cause outbreaks of disease throughout the world. The UK is currently experiencing an upsurge due to organisms of groups B and C. There is substantial under-reporting of meningococcal disease, only meningitis currently being notifiable. All significant meningococcal strains should be typed by a reference laboratory. New approaches to vaccine development permit cautious optimism for the future. PMID- 3325121 TI - Management of Guillain-Barre syndrome. AB - Guillain-Barre syndrome is a predominantly motor polyradiculoneuropathy in which neurological deficit reaches a peak within 1 month of onset. Seventy per cent of patients recover within 1 year, but 10% die and 20% have residual disability. Plasma exchange is advocated for severe cases early in the course of the disease but the role of steroids has yet to be determined. PMID- 3325122 TI - Prostatic ultrasound. AB - Ultrasonography is a useful method of imaging the prostate gland. Perrectal ultrasonography may be used in the assessment of the enlarged or nodular prostate. Benign hyperplasia, prostatitis and prostatic carcinoma can be differentiated. In the management of patients with prostatic cancer, per-rectal ultrasound scanning is invaluable in the diagnosis, staging, treatment and follow up of the disease. PMID- 3325123 TI - Assessing blood volume, blood loss and blood replacement. AB - Blood volume has two components: red cell volume, which can be measured with reasonable precision, and plasma volume, which is more difficult to measure accurately. Measurement of blood loss is discussed with respect to clinical practice and research, and topical issues concerning blood replacement are reviewed. PMID- 3325124 TI - Myelodysplasia. AB - The myelodysplastic syndrome has recently explained obscure anaemias, neutropenias and thrombocytopenias to haematologists, yet the concept remains puzzling to doctors outside the field. This review aims to introduce to non specialists one of the commonest blood disorders in the elderly. PMID- 3325125 TI - The painful heel. AB - The painful heel syndrome is a common complaint of the middle-aged and elderly. Most patients have no associated disease, except obesity, but young men should be carefully evaluated for ankylosing spondylitis or reactive arthritis. The majority of cases respond to appropriate heel padding, corticosteroid injection or a specially designed insole. PMID- 3325126 TI - Monoamine oxidase inhibitors: have they a place, have they a future? AB - The legacy of the hepatotoxic effect and the "cheese reaction" of monoamine oxidase inhibitors still overshadows these useful drugs, despite near-resolution of many of the problems. This short article reviews the indications, adverse effects and progress and future of these agents in psychopharmacology. PMID- 3325127 TI - Ultrasound diagnosis of Achilles tendon pathology in runners. AB - The great upsurge in popularity of running activities has increased the number of athletes presenting with pathology of the Achilles tendon. A clinical and ultrasonic study was performed on 47 middle and long distance runners referred to the Authors with such problems. The results of this study can be grouped as follows: 1. paratendonitis: enlargement of the antero-posterior diameter of the tendon, and hyperechogenicity of Kager's triangle; 2. tendonitis (with or without paratendonitis): thickening of the tendon, with the presence of degenerative nodules; 3. enthesopathy: thickening of the distal part of the tendon, enlargement of the hypoechogenic area behind the tendon itself and microcalcification. PMID- 3325128 TI - Presence of renin in primary neuronal and glial cells from rat brain. AB - Immunocytochemical and biochemical techniques have been utilized in the present study to characterize renin in brain cell cultures. With the use of renin specific antibody, positive renin staining was seen in neuronal and in astrocytic glial cells using the peroxidase-antiperoxidase method. Renin concentration was pH-dependent with highest concentrations at 5.5, decreasing from pH 6.0 to 6.5. At pH 7.4 no renin was detectable in either glial or neuronal cells. The contribution of cathepsin D to the measured renin was about 10% at pH 5.5; 7% at pH 6.0 and 3% at pH 6.5. Comparison of glial with neuronal cells from WKY rats revealed significantly elevated renin at pH 5.5 in glial cells. No difference was seen between glial and neuronal renin levels in WKY rats at pH 6.0 and 6.5. At pH 5.5 and 6.0 renin was significantly increased in neuronal cells of SHR compared to WKY, whereas at pH 6.5 no difference was observed. The renin concentration in cells kept for 2 days in serum-free medium did not differ from those measured in cells kept in serum-containing medium. The generated peptide was identified as [Ile5]Angiotensin I on reversed-phase HPLC. PMID- 3325129 TI - Pregnanolone, a metabolite of progesterone, stimulates LH-RH release: in vitro and in vivo studies. AB - The effect of 5 beta- and 5 alpha-reduced progestins on luteinizing hormone releasing hormone (LH-RH) release was examined using either an in vitro superfusion or an in vivo push-pull perfusion (PPP) technique. Ovariectomized rats (at least 6 days post operation: OVX) were implanted subcutaneously in the neck region with a silastic capsule containing 17 beta-estradiol (235 micrograms/ml: E2). Two days afterwards, these OVX + E2 rats were subjected to experimental conditions. Pregnanolone(5 beta-pregnane-3 beta-ol-20-one) at a low concentration of 0.01 ng/ml and an apparent latency of 1 h stimulated in vitro LH RH release from superfused hypothalamic fragments containing the preoptic anterior hypothalamic-mediobasal hypothalamic area (POA-AHA-MBH). The stimulatory effect of pregnanolone required estrogen-priming and a pulsatile mode of administration. In addition, the effect appeared quite specific since other closely related steroids such as epipregnanolone, R-5020 and 5 alpha-DHP were ineffective. In OVX + E2 rats bearing a push-pull cannula (PPC) in the hypothalamic area, in vivo infusion of repetitive pulses of pregnanolone through the PPC was also effective, confirming in vivo the stimulatory effect of pregnanolone on LH-RH release obtained from in vitro preparations. In these experiments, the same OVX + E2 rats served both as an experimental animal receiving pulses of pregnanolone and as a control subject when perfused only with medium after a week interval. The basal release rate of LH-RH and the response to pulsatile pregnanolone were variable among animals apparently due to different locations of PPC in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325131 TI - [Present status of drug addiction]. PMID- 3325130 TI - Evidence for differential regulation of corticotropin-releasing factor and vasopressin immunoreactivities in parvocellular neurosecretory and autonomic related projections of the paraventricular nucleus. AB - A combined retrograde transport-immunohistochemical method was used to compare the numbers of corticotropin-releasing factor (CRF) and vasopressin immunoreactive neurons in the paraventricular nucleus of the hypothalamus (PVH) that could be retrogradely labeled after tracer injections in the dorsomedial medulla or the spinal cord in untreated, colchicine-treated, and adrenalectomized (ADX) male rats. In untreated animals, very few CRF-stained cells were retrogradely labeled after tracer injections in either target, while a modest number, comparable to that seen in previous studies, of vasopressinergic cells were found to project to one or both structures. Animals pretreated with colchicine, a non-specific inhibitor of axonal transport, displayed CRF immunoreactivity in a small percentage of retrogradely labeled neurons in the PVH; the number of retrogradely labeled vasopressin-immunoreactive cells was comparable to that seen in untreated rats. Despite the fact that ADX animals displayed enhanced immunostaining for both peptides in the parvocellular division of the PVH, the number of retrogradely labeled cells stained for each peptide was similar to that seen in controls. The results establish that CRF is contained within the long descending projections of the PVH, and are consistent with the view that adrenal steroid withdrawal preferentially enhances the expression of CRF and vasopressin in parvocellular neurosecretory neurons. PMID- 3325132 TI - [Outline of a system for the care and assistance of drug addicts]. PMID- 3325134 TI - [Fate of drug addicts]. PMID- 3325133 TI - [Cocaine and toxicity of endogenous neurotransmitters]. PMID- 3325135 TI - [Diversified therapeutics]. PMID- 3325136 TI - [Certificate of aptitude for physical and sport activities]. PMID- 3325137 TI - [Proposed ordinance to change Article 6 of decree No. 51-953 of 9 July 1951 defining the medical contraindications of BCG vaccination]. PMID- 3325138 TI - [Request for extension of the use of polyphosphates (E 450) and sorbitol (E 420) to fish preparations with a "surimi" base]. PMID- 3325140 TI - [Eulogy of Georges Brouet (1905-1986)]. PMID- 3325139 TI - [Use of a filtration enzyme with dominant beta-glucanase activity produced by Disporotrichum dimorphosporum, in beer brewing]. PMID- 3325142 TI - [The media and AIDS]. PMID- 3325141 TI - [The media and cancer]. PMID- 3325143 TI - [The media and procreation]. PMID- 3325145 TI - [The media and personal colloquy]. PMID- 3325144 TI - [The media and procreation]. PMID- 3325146 TI - [The media and deontology]. PMID- 3325147 TI - [Medicine, physicians and the media]. PMID- 3325148 TI - [Immunological protection against tetanus]. PMID- 3325149 TI - [Orientation of injured patients starting with emergency medical assistance services]. PMID- 3325150 TI - [Use of alcalase 0.6 L for obtaining protein hydrolysates intended for special diets]. PMID- 3325151 TI - [Request for authorization of the ionizing treatment of a film made of plastic material, with the aim of obtaining several unusual functional properties]. PMID- 3325152 TI - [Use of citric acid in the filling of apple tarts]. PMID- 3325153 TI - [Treatment with ionizing radiation of liquid, dehydrated and frozen egg white]. PMID- 3325154 TI - [Occupation of the Academy of Medicine by medical students in May 1987]. PMID- 3325155 TI - [Psychotropic drugs and accidents]. PMID- 3325156 TI - Open label study of ioxaglate in coronary angiography. Multicentre clinical trial. AB - The diagnostic quality and patient tolerance of coronary arteriography using ioxaglate as contrast medium was assessed in 455 patients in a multicentre open label study. Only 0.2% of procedures were considered not diagnostic and side effects were considered nonexistent or mild in the majority of patients. There was no neurological effects such as convulsions, hemiparesis or visual disturbances. PMID- 3325157 TI - The fifth decade of the Canadian Ophthalmological Society. PMID- 3325158 TI - Orbital lymphoproliferative and inflammatory lesions. AB - We reviewed the records and biopsy specimens of 38 patients with clinically similar orbital lymphoproliferative and low-grade inflammatory lesions referred to one ophthalmologist at the University of British Columbia between 1977 and 1984. Twenty-six patients had lymphoproliferative lesions, the main feature being a densely cellular population of small lymphocytes. This group was further divided into reactive lymphoid hyperplasia, malignant lymphoma, Hodgkin's disease and atypical lymphoid hyperplasia. Symptoms and signs were similar within the subgroups. The mean length of follow-up was 3.7 years. Of the 26 patients 14 had extraorbital lymphoproliferative disease, 9 had orbital recurrences and 2 died of widespread disease. Twelve patients had inflammatory lesions with distinctly different histologic features from those of the lymphoproliferative group. Symptoms and signs were similar to those in the latter group. The mean length of follow-up was 2.1 years. Four of the 12 had orbital recurrences; none had extraorbital disease or died of their disease. We feel that orbital lymphoproliferative lesions can easily be separated from clinically similar low grade inflammatory lesions histologically and that they should be staged and followed like small lymphocytic lymphomas. Guidelines are given for handling these specimens in the laboratory. PMID- 3325159 TI - Behavioral intervention for health promotion: developing a partnership between research producers and research consumers. PMID- 3325161 TI - A case of human rabies in western Canada. PMID- 3325160 TI - Worksite smoking cessation: current progress and future directions. PMID- 3325162 TI - A proposed protocol for culturally relevant nursing psychotherapy. PMID- 3325163 TI - The interface of psychiatry and medicine: towards integrated health care. AB - Establishment of closer links with medicine in clinical work, research and teaching represents a major achievement of psychiatry in this century. Development of general hospital psychiatry has played a key role in this regard. Numerous studies quoted in this article have documented a large overlap between psychiatric and physical morbidity in the community and in all health care settings. These findings argue most strongly in favour of continued efforts to expand all activities at the interface of psychiatry and medicine, with truly integrated health care as the ultimate goal. PMID- 3325164 TI - [Unemployment and mental health]. AB - Evidence linking unemployment with psychiatric morbidity is available since the thirties, but it is only in the seventies that a renewed research interest on this subject took place. Two research strategies seem to be emerging: an "ecological" approach establishing correlations between economical and health indicators for a given population. Another approach focuses on the psychiatric morbidity of samples of individuals who have lost their job compared to matched control groups of individuals still employed. Many of those studies did not limit themselves on the mental health of the unemployed but on the "rippling" effect of unemployment on the family and community. Many aspects of the consequences of unemployment on mental health remain to be explored such as the effects of long term unemployment, unemployment among women. Methods of emotional supportive interventions for the unemployed need also to be explored. Furthermore the effects of a high level of unemployment on the programs of deinstitutionalization of the chronic mentally ill as well as the mentally handicapped should be evaluated. PMID- 3325165 TI - Relationship of H1(0) histone to differentiation and cancer. AB - The H1(0) histone was first described by Panyim and Chalkley in 1969 as a new electrophoretic band found with histones of non-replicating tissues. Tissues which are active in DNA replication such as ascites tumor cells or thymus cells were reported to lack this band. In this respect the H1(0) histone differs from the bulk of histones which are generally maintained in a constant ratio with respect to each other and to DNA. An inverse relationship between H1(0) histone levels and growth rate was suggested by the decrease in H1(0) histone concentration during regeneration of the pancreas and liver. The synthesis of H1(0) is unusual but not unique in that, unlike the major histone species, it is not restricted to the S phase of the cell cycle. Although there is a general trend for the levels of H1(0) histone to be lower in neoplastic than normal tissues, exceptions have been observed. Compounds such as sodium butyrate and dimethylsulfoxide, which can induce differentiated properties in neoplastic cells, can bring about the accumulation of increased amounts of H1(0) histones. The relative magnitude of these effects exhibits cell-type specificity. There are two H1(0) histone subtypes (a and b) with ratios which differ according to the tissue examined and whose relative importance is not known. The levels of H1(0) histone appear to be more closely related to the degree of differentiation than to the proliferative activity of cells. PMID- 3325166 TI - The structure of the neuraminic acid-containing capsular polysaccharide of Escherichia coli serotype K9. AB - The acidic capsular polysaccharide isolated from Escherichia coli O9:K9:H12 was investigated by using n.m.r. spectroscopy, methylation analysis, periodate oxidation, and bacteriophage-borne enzyme degradation. The polysaccharide, the structure of which is shown below, is the third E. coli capsular polysaccharide reported to contain neuraminic acid, the others being the K1 and K92 polysaccharides, and it is the first in the E. coli series shown to contain a 4 linked neuraminic acid unit. (formula; see text). PMID- 3325167 TI - The Ross osteounification tooth replacement system: a clinical case report of an immediate extraction site. PMID- 3325168 TI - The first human organ transplant: a tooth. PMID- 3325169 TI - Osseous grafting in periodontal therapy, Part I: Osseous graft materials. PMID- 3325170 TI - Calcium uptake into guinea-pig trachealis: the effect of epithelium removal. AB - Removal of the epithelium from preparations of guinea-pig airways in vitro increases the responsiveness of the smooth muscle of normal and ovalbumin sensitized animals to a number of contractile agents. To determine if epithelium removal results in an increase in Ca2+ entry into the smooth muscle, the effect of removing the epithelium on Ca2+ uptake into the trachealis smooth muscle was studied using a modified La3+-technique. KCl increased Ca2+ uptake in the presence and absence of the epithelium in control and sensitized animals. Methacholine did not promote Ca2+ uptake, whether or not the epithelium was present, in either control or sensitized animals. Ovalbumin did not stimulate Ca2+ uptake into the trachealis of sensitized animals. These results indicate that the increase in responsiveness of airway smooth muscle seen on epithelium removal is not a consequence of a facilitation of Ca2+ entry into the muscle. The increased responsiveness to methacholine in control animals, and to ovalbumin in preparations in tension studies in epithelium-free tissues from sensitized animals, cannot be explained by an increased availability of extracellular Ca2+ into the muscle, but, rather may reflect some other effect of the epithelium derived modulatory factor. PMID- 3325171 TI - Alternatives to restorations. PMID- 3325172 TI - Fixture placement. PMID- 3325173 TI - Tooth preparation. PMID- 3325174 TI - Immunomodulation by cancer chemotherapeutic agents. AB - Cytotoxic agents may specifically interfere with the different components of cellular and humoral immunity, and consequently modulate the responses in opposite directions, by not only inducing impairment but also augmenting some immune functions. They may also modulate tumor antigenic expression, leading to increased immunogenicity. Glucocorticoids at sufficiently high concentrations can inhibit virtually any function of lymphocytes, NK cells, monocytes and macrophages. Azathioprine and other antimetabolites, such as 6-mercaptopurine, methotrexate and cytarabine, have a similar generalized immunosuppressive activity and may be used therapeutically for this purpose in the clinic. Cyclophosphamide exerts an immunosuppressive or an immunostimulating effect when given at high or low doses, respectively. The marked Cy-induced inhibition of T suppressor lymphocytes, the predominant immune cell population in cancer patients favoring tumor growth, may have important therapeutic significance. DX enhances proliferation of lymphocytes in the presence of mitogens, but may inhibit antibody production; it also increases the tumoricidal activity of monocytes and macrophages and does not alter substantially NK cytolytic activity. A detailed study of drug effects on the tumor and host immune system may contribute to their more rational use in cancer chemotherapy with regard to toxicity and efficacy. PMID- 3325175 TI - Amikacin plus ceftazidime versus amikacin plus piperacillin versus amikacin plus aztreonam in infections in neoplastic patients with granulocytopenia. AB - Sixty granulocytopenic patients (granulocytes less than 1000/mm3) affected with solid tumors, previously submitted to antiblastic therapy and with infections, were treated with three antibiotic combinations: amikacin + ceftazidime, amikacin + piperacillin or amikacin + aztreonam. In 68% of the cases the infections were due to gram-negative and in the remaining 32% to gram-positive microorganisms. The results obtained with the three treatments show a slight but significant statistical difference (p less than 0.05), due to the greater efficacy of the amikacin + ceftazidime combination on gram-positive and amikacin + aztreonam on gram-negative bacteria. PMID- 3325176 TI - Results of clinical trials with ciprofloxacin in Italy. AB - The Authors report about the results of 23 clinical trials carried out in Italy with oral formulations of BAY o 9867 (ciprofloxacin) in the treatment of infections in various sites of the body. Altogether 644 patients were evaluated for therapeutic efficacy; positive clinical results were obtained in 95 to 100% of the treated patients, according to the site of the infection. The bacteriological examinations performed on 575 cases show eradication in 89.22%, eradication with relapse or reinfection in 2.26%, and persistence in 6.09%. Adverse reactions were observed in 38 out of 646 patients (5.89%); none of them, however, were severe or irreversible. PMID- 3325177 TI - Role of SCN in daily rhythms of plasma glucose, FFA, insulin and glucagon. AB - The daily changes in plasma glucose, FFA, insulin and glucagon concentrations in rats under 12 hr-12 hr light-dark conditions, and the role of the suprachiasmatic nucleus (SCN) of the hypothalamus in these changes were examined. In sham operated rats, the four parameters showed significant daily rhythms. However, after bilateral lesions of the SCN, daily rhythms could not be detected in these parameters under the present experimental conditions. Furthermore, after the SCN lesions the plasma glucose concentration remained at the minimum level of that in sham-operated rats, while the plasma insulin and glucagon concentrations reduced to approximately the mean level and about half the minimum level of sham-operated rats, respectively, and the FFA concentration lowered to somewhat below the minimum level. Gradual increase in the plasma insulin concentration at the end of the light period was observed in intact rats even after starvation for 24 hr. These findings suggest that the SCN is essential for generation of the daily changes in the plasma glucose, FFA, insulin and glucagon concentrations and also that it plays critical roles in regulation of the secretion of pancreatic hormones. The gradual increase in the plasma insulin level observed at the end of the light period is discussed in connection with initiation of spontaneous feeding behaviour. PMID- 3325178 TI - Synthesis and anti-platelet aggregating activity of 3-hetero analogues of (+) 9(O)-methano-delta 6(9 alpha)-prostaglandin I1. PMID- 3325179 TI - Purification and characterization of the product of chemically synthesized human growth hormone gene expression in Escherichia coli. PMID- 3325180 TI - Conjugative metabolism of 4-methylumbelliferone in the rat liver: verification of the sequestration process in multiple indicator dilution experiments. PMID- 3325181 TI - Synthesis of peptide chloromethyl ketones and examination of their inhibitory effects on human spleen fibrinolytic proteinase (SFP) and human leukocyte elastase (LE). PMID- 3325182 TI - Effect of ultrasonic irradiation on the dissociation of antigen-antibody complexes. Application to homogeneous enzyme immunoassay. PMID- 3325183 TI - Streptococcal diseases worldwide: present status and prospects. AB - Infections caused by streptococci pathogenic for man are some of the most common bacterial diseases in temperate zones and occur very frequently in tropical and subtropical countries. The highest morbidity occurs from infections caused by group A streptococci; these infections can lead to rheumatic fever and acute glomerulonephritis. The incidence of rheumatic fever and the prevalence of rheumatic heart disease are several times higher in tropical countries than temperate countries.Recent developments in fundamental and applied research are throwing light on various aspects of the problem, e.g., the rapid (non-culture) identification of group A streptococcal infection. Analyses of the chemical structure of the M-protein molecule of group A streptococcus and of the biological properties of the epitopes of the M-protein have provided encouraging results. Furthermore, synthetic analogues of the protective immunodominant polypeptides of the M-protein have been prepared. The prospect of a streptococcal vaccine for preventing group A streptococcal diseases is thus more realistic.The control of infections caused by group B streptococci is important for the health of neonates. The identification of the chemical structure of the major group B streptococcal types may lead to development of a vaccine in the future. An alternative approach would entail the use of anti-group-B immunoglobulins, but a number of questions have to be answered before the new control measures can be introduced. The streptococci causing bacterial pneumonia, subacute bacterial endocarditis and possibly dental caries have been widely studied and promising advances have been made towards the introduction of better control of the diseases caused by these pathogens. PMID- 3325184 TI - The epidemiology of drug resistance of malaria parasites: memorandum from a WHO meeting. AB - This Memorandum presents current knowledge concerning the epidemiology of drug resistance of malaria parasites and outlines 33 research proposals which could lead to a better understanding of that epidemiology and to a better management of the problem. PMID- 3325185 TI - Reduction in incidence and prevalence of Plasmodium falciparum in under-5-year old children by permethrin impregnation of mosquito nets. AB - The malaria incidence and prevalence rates among children who slept under permethrin-impregnated mosquito nets in four villages near Madang, Papua New Guinea, were compared with the rates among children who slept under unimpregnated nets in four paired control villages. Immediately following a parasitological survey in the eight villages, malaria parasites were cleared from the children with chemotherapy, and the mosquito nets in the four experimental villages were impregnated with permethrin. Follow-up parasitological surveys were performed 4 and 10 weeks later. Sporozoite rates in female mosquitos of the Anopheles punctulatus complex decreased significantly in two of the experimental villages after impregnation. Also, the incidence of Plasmodium falciparum between the 4 week and 10-week surveys was significantly lower among the 0-4-year olds in villages with impregnated nets than in those with unimpregnated nets, leading to reduced prevalence of P. falciparum in this age group. Use of permethrin impregnated nets had no effect on the incidence or prevalence of P. falciparum among 5-9-year olds or on that of P. vivax among the 0-4- or 5-9-year olds. PMID- 3325186 TI - In vivo response of Plasmodium falciparum to chloroquine in pregnant and non pregnant women in Siaya District, Kenya. AB - Chemoprophylaxis using chloroquine (CQ) in suppressive doses has been recommended to protect pregnant women in malarious areas from the adverse effects of malaria during pregnancy. In a malaria-endemic area of western Kenya with CQ-resistant Plasmodium falciparum, we determined the prevalence and density of falciparum infection in gravid and nulligravid women and compared the in-vivo parasite response to CQ using two regimens: 25 mg/kg body weight (CQ25) divided over a period of three days (for high-density parasitaemias) and 5 mg/kg body weight (CQ5) weekly for 4 weeks (for low-density parasitaemias). P. falciparum infections were present in 102 (42%) of 244 pregnant women. A greater proportion of primigravidae were parasitaemic (68%) than nulligravidae (50%, P=0.02) or multigravidae (33%, P <10(-6)). Primigravidae showed a higher geometric mean parasite density. In the CQ25 treatment group, failure to clear parasites by day 7 was more common in primigravidae than nulligravidae (P=0.008) or multigravidae (P=0.15). In the CQ5 treatment group, primigravidae were more likely to show increasing parasite density than nulligravidae or multigravidae.In this area of Kenya, virtually all women in their first pregnancy are exposed to malaria and are at greatest risk for malaria infection; compared with other women, they show higher parasite densities and are least likely to respond to chloroquine treatment in areas of chloroquine resistance. Malaria control strategies might be targeted to this group of women, but we are pessimistic about the efficacy of weekly CQ5 where there is chloroquine resistance. PMID- 3325187 TI - Malaria on the Thai-Burmese border: treatment of 5192 patients with mefloquine sulfadoxine-pyrimethamine. AB - Multidrug-resistant falciparum malaria is a major health problem along the Thai Burmese border. From July 1985 until December 1986 a total of 5192 patients with falciparum malaria (1734 males, 3458 females) from this area were given supervised treatment with the combination mefloquine-sulfadoxine-pyrimethamine (MSP). The radical cure rate, assessed 21 days after drug administration, was 98.4% for the first 1975 patients, and 98.8% when assessed at 28 days for the remaining 3217 patients. In 3.8% of cases, parasites were still detected in peripheral blood smears on day 7 after treatment but this had fallen to 0.27% by day 9. Adverse reactions among the first 1975 patients were: vertigo (7.5% of patients), vomiting (5.8%), epigastric pain (0.6%), and transient confusional state (one case). MSP is an effective and well-tolerated drug for the treatment of drug-resistant falciparum malaria; however, delayed parasite clearance may give a false impression of RII resistance. PMID- 3325188 TI - HIV infection and routine childhood immunization: a review. PMID- 3325191 TI - Development and clinical application of sensitive enzyme immunoassay for macromolecular antigens--a review. AB - Radioimmunoassay has been a powerful tool to measure haptens and antigens which are important for the investigation and diagnosis of diseases, especially endocrine disorders. However, the use of radioisotopes in radioimmunoassay suffers from serious disadvantages. Radioisotope-labeled reagents are unstable and hazardous to health. The disposal of radioactive wastes is not easy. Furthermore, the sensitivity of radioimmunoassay is limited by the detection limit of radioisotope that depends upon the half-life. The detection limit of the most widely used radioisotope, 125I, with a half-life of 60 days is 5 to 10 amol, when it is carrier-free. By contrast, the use of enzymes has obvious advantages. Some enzymes are very stable and cause no health hazards or waste disposal problems, provided that appropriate substrates are chosen. The detection limits of some enzymes are lower than that of 125I and will be further improved in the future. Therefore, enzyme immunoassay is potentially more sensitive than radioimmunoassay. This article reviews the development and clinical application of sensitive enzyme immunoassay for macromolecular antigens, which has been replacing radioimmunoassay. PMID- 3325189 TI - Psychology and health: contributions of psychology to the improvement of health and health care. AB - Psychology as both a science and a profession has been closely identified with other disciplines in the broad field of health since the turn of the present century. Recent advances in health care have reinforced the growing belief that the promotion of health and the prevention and treatment of illness can be greatly enhanced by incorporating the scientific findings and modern techniques of psychology into everyday practices. This review outlines the contributions of psychology to health care throughout the world; only some of the most timely and relevant issues are mentioned, together with examples of current work in the field. After an introductory overview, special attention is given to each of the major areas within the broad field of health care where psychological applications have been particularly useful. PMID- 3325190 TI - Comparison of nasal responsiveness to histamine, methacholine and phentolamine in allergic rhinitis patients and controls. AB - In a selected group of rhinitis patients with an IgE-mediated allergy to house dust mites the nasal response to insufflation of histamine chloride, methacholine and phentolamine was demonstrated to be higher than in a control group. With the methods used histamine chloride was better at discriminating between healthy subjects and patients than methacholine or phentolamine. This discrimination was shown by assessing the severity of reflex-mediated symptoms such as the number of sneezes and the amount of secretion, and not by differences in nasal airway resistance. PMID- 3325192 TI - Clinical and biological significance of an isozyme tumor marker--PLAP. AB - In 1930 the determination of serum alkaline phosphatase in patients with bone or liver disease ushered in the era of clinical enzymology. The association of elevated (bone) alkaline phosphatase in serum of patients with osteogenic sarcoma was the first evidence that tumor cells themselves produced the enzyme. It became clear, however, in the 1960s that the serum alkaline phosphatase was not a single enzyme but consisted of a family of isozymes originating from liver, bone, intestine, and placenta. This was a consequence of the introduction of a combination of electrophoretic separations, heat inactivation, and organ-specific amino acid inhibitors. This combination of measurements made possible the demonstration of a serum alkaline phosphatase of lung cancer origin, as confirmed by the histochemical visualization in lung cancer of the Regan Isozyme (placental alkaline phosphatase-PLAP). At present, the measurement of PLAP has its greatest utility as a tumor marker in seminoma and ovarian cancer. A PLAP-like isozyme in normal testis and ovary is expressed in these and other neoplasias and appears to be related to rare alleles of placental alkaline phosphatase. Current studies have utilized a panel of monoclonal antibodies to detect useful epitopes that suggest that PLAP and PLAP-like isozymes are coded by different genes. The PLAP gene has now been cloned and sequenced by Millan and others. This fundamental new information is providing a base line that will make it possible to explain the overlapping specificities of intestinal and placental isozymes, the degree of uniqueness of the PLAP-like isozyme, the precise mechanism of uncompetitive inhibition by L-phenylalanine and the evolutionary history of the alkaline phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325193 TI - Lipolytic enzymes as markers of induction and differentiation. AB - Factors leading to microsomal enzyme induction are associated with hypertriglyceridemia in man. Phenobarbital (PB) increases hepatic synthesis of triglyceride but lowers its serum concentration in rats due to increased postheparin plasma activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL); these changes are accompanied by increased activity of these lipolytic enzymes in adipose tissue and liver. The present work explores the cellular mechanisms whereby PB increases the tissue content of these enzymes, using primary cultures of rat liver hepatocytes and a continuous cell line of mouse fibroblasts (preadipocytes) that undergo differentiation into mature fat cells. Secretion and synthesis of HTGL in primary rat hepatocytes increased 50% with insulin; when PB was added with insulin, activity was enhanced an additional 50%. By contrast, insulin inhibited HTGL secretion from the well differentiated rat hepatoma cell line, FU-5-5, C8, and this inhibition was partly overcome by PB. These results suggest that different control mechanisms govern the synthesis and secretion of HTGL in normal rat liver cells and hepatoma. In cultured pre adipocytes (3T3-F442A) insulin promoted differentiation when added to confluent cultures. PB (0.5 mM) resulted in marked enhancement of conversion of adipocytes characterized by a two- to threefold increase in extracellular LPL and a 10-fold increase in intracellular enzyme. These results suggest that PB promotes conversion of uncommitted cells into pre-adipocytes at an early stage in the differentiation of adipose tissue. PMID- 3325194 TI - Sandwich enzyme immunoassay for human interleukin-1 alpha produced in vitro by peripheral blood mononuclear cells. PMID- 3325196 TI - Successful management of Cushing's disease during pregnancy by transsphenoidal adenectomy. AB - Pregnancy in patients with Cushing's syndrome is rare. It is associated with a high fetal loss, increased frequency of preterm labour and excessive maternal morbidity. We describe a patient who became pregnant while investigations for hypertension were being done. Cushing's disease was diagnosed and the patient had transsphenoidal pituitary surgery at 22 weeks gestation. To our knowledge this is the first time this operation has been done during pregnancy for this condition. Cushing's disease was controlled, but because of worsening hypertension, she had a caesarean section at 30 weeks gestation. Subsequently her blood pressure fell and her hydrocortisone replacement therapy is being withdrawn. Her daughter is now thriving after initial problems with pneumothoraces. PMID- 3325195 TI - Determination of transcortin in serum by polyethylenglycol enhanced immunonephelometry. A comparison with equilibrium dialysis and radioimmunoassay. AB - A method for immunonepholometric determination of transcortin has been developed. It is based upon a polyethylenglycol (PEG) enhanced immunonephelometric response using a commercial transcortin antiserum in the assay. It was found that pretreatment of the serum samples with 10% (w/v) PEG 6000 was a necessity in order to obtain satisfactory low blank values. The immunonephelometric assay showed a good correlation with transcortin concentrations as calculated from cortisol binding experiments (r = 0.9501, n = 26). The intraassay coefficient of variation for a standard serum was found to be 3.2% (n = 50) and for a pregnancy serum pool 2.6% (n = 50). The interassay coefficient of variation in ten consecutive analyses of thirteen samples was found to be 7.4%. The sensitivity allows detection of transcortin in 5 microliters of serum. The average concentration in male serum was 35 mg/l (n = 55), in female serum 36 mg/l (n = 55) and in serum from third trimester pregnant women 81 mg/l (n = 30) which agrees with the results in previously published reports. PMID- 3325198 TI - Active and inactive renin-like enzymes in the brain of spontaneously hypertensive rat. AB - Renin-like enzyme(s) in the brain of spontaneously hypertensive rat (SHR) were activated unequivocally by trypsin. The highest concentration of the active renin like enzyme was localized in the hypothalamus (1.03 +/- 0.25 ng angiotensin I/mg of protein per h, mean +/- S.D.), followed by the striatum (0.51 +/- 0.21), thalamus (0.40 +/- 0.08), midbrain (0.33 +/- 0.04), medulla oblongata (0.25 +/- 0.01), cerebral cortex (0.21 +/- 0.03), and cerebellum (0.14 +/- 0.03), while the highest concentration of the inactive renin-like enzyme was localized in the hypothalamus (0.86 +/- 0.17), followed by the striatum (0.47 +/- 0.15), thalamus (0.32 +/- 0.09), cerebellum (0.29 +/- 0.04), midbrain (0.26 +/- 0.02), cerebral cortex (0.24 +/- 0.04), and medulla oblongata (0.10 +/- 0.03). The active renin like activity in the thalamus of SHR was significantly lower than that of age- and sex-matched normotensive Wistar-Kyoto (WKY) rats. Furthermore, the inactive renin-like activity in the striatum, thalamus, cerebellum, midbrain, and medulla oblongata of SHR was significantly lower than that in the corresponding areas of WKY rats. Although the precise mechanisms underlying the conversion of inactive to active renin-like enzyme in the brain remain to be resolved, these results may offer a new aspect for the role of the brain renin-angiotensin system in the initiation and/or development of hypertension of SHR. PMID- 3325197 TI - A study of beta-cell function after glucagon stimulation in thalassaemia major treated by high transfusion programme. AB - An increased incidence of diabetes mellitus and glucose intolerance has been reported in thalassaemia major treated with a high transfusion programme (HTP). To investigate beta-cell function, serum immunoreactive insulin (IRI), C-peptide (CP) and glucose were measured fasting and at 3, 6 and 10 min after i.v. administration of 1 mg glucagon in 20 thalassaemia patients treated by many transfusions and in nine healthy control subjects. Fasting C-peptide concentrations (mean +/- SEM) were higher in the thalassaemic group (2.15 +/- 0.17 ng/ml) than in the controls (1.41 +/- 0.13 ng/ml). After stimulation with glucagon, C-peptide concentrations were consistently higher (P less than 0.01) by approximately 50% in the thalassaemic than in the control group (5.29 +/- 0.31 vs 3.36 +/- 0.21 ng/ml, at 3 min; 5.22 +/- 0.30 vs 3.53 +/- 0.21 ng/ml at 6 min and 4.69 +/- 0.27 vs 3.30 +/- 0.17 ng/ml after 10 min). Plasma IRI concentrations increased in both groups after glucagon stimulation but were not significantly different. The glucose values were approximately 15% higher at each sampling time in the thalassaemic group than those of the normal subjects. It is concluded that disturbances in carbohydrate metabolism in thalassaemia major treated with HTP are the consequence of hepatic cirrhosis which accompanies secondary haemosiderosis, and possibly iron deposition in the beta-cells of the pancreas. PMID- 3325199 TI - Tryptic generation of an angiotensin binding substance. AB - Following trypsin treatment of rat or human plasma, the level of angiotensin I, generated by renin, can be significantly underestimated by radioimmunoassay due to tryptic generation of an angiotensin binding substance. The precursor of the binding substance (void volume-AcA 44 gel) was converted by trypsin to 45K. Analogous to PRC methodology, known concentrations of angiotensin I were added to control and trypsin treated human plasma after the renin incubation step to determine the influence of the binding substance on the measured levels of generated angiotensin I. Using this technique, renin levels in trypsin exposed plasma were approximately two fold higher than when measured by single point conventional assay. If plasma levels of the binding precursor change in response to renin stimulation or suppression, its activation during the trypsin treatment step of the renin assay may explain the relative lack of change of inactive renin observed following numerous in vivo maneuvers. PMID- 3325200 TI - Effects of captopril on sympathetic control of the heart and vasculature in dogs. AB - Experiments were conducted in pentobarbital anesthetized dogs to investigate the effects of captopril on sympathetic neuronal control of the heart and hindlimb vasculature. Captopril, 3.1 mg/kg, i.v. produced marked reductions in blood pressure and hindlimb perfusion pressure, an observation consistent with the high plasma renin activity in the test animals. Increments in hindlimb perfusion pressure elicited by electrical stimulation of the lumbar sympathetic chain were also significantly reduced following captopril administration (p less than .002). The subsequent administration of a ten fold higher dose of captopril, 31.0 mg/kg, produced no further attenuation of the neurally mediated responses. In contrast to the decreased vascular responses to nerve stimulation after captopril, the tachycardia produced by stimulation of pre- or post-ganglionic neurons to the stellate ganglion were not altered. The results of the present study suggest that captopril acts by inhibiting vascular sympathetic neuronal function when the activity of the renin-angiotensin system is elevated. The attenuation of neurally mediated vasoconstriction may be due to the interruption of angiotensin II formation, thereby, preventing the facilitatory effects of angiotensin on sympathetic neurons. PMID- 3325201 TI - Inflammatory cells in murine visceral leishmaniasis express a dendritic cell marker. AB - Immunohistological studies of the murine liver following Leishmania donovani infection have been performed. We describe here the identification of cells expressing a recently defined dendritic cell marker, as detected by monoclonal antibody NLDC 145. Such cells are numerous in the developing inflammatory foci but are not detected individually at any other site in the infected liver. This finding suggests that mature tissue DC are not recruited during infection and that expression of this antigen is under precise microenvironmental control. PMID- 3325202 TI - Comparison between autoantibodies in malaria and leprosy with lupus. AB - Sera from 16 patients with falciparum malaria, 16 patients with vivax malaria and 31 patients with leprosy were tested for autoantibodies to intracellular proteins and nucleic acids. Precipitating antibodies to soluble protein extracts were not detected in any serum. Sera from malaria patients showed prominent immunofluorescence staining of the HEP2 nuclear membrane as well as frequent 75% (24/32) and intense Western blot reactivity. In contrast, only 20% and 36% of patients with leprosy had positive immunofluorescence or positive immunoblots respectively, and reactivity was weak in most cases. Neither the malaria nor leprosy sera contained autoantibodies with specificities similar to the characteristic lupus autoantibodies such as double stranded DNA (dsDNA), Ro/SSA, La/SSB, Sm, RNP and P proteins. Low levels of antibodies to single stranded (ssDNA) were however found in 11 (34%) malaria sera and in seven (23%) leprosy sera. Thirteen percent of patients with leprosy had anti-histone antibodies. These findings demonstrate considerable differences in the capacity of infectious agents to induce autoantibodies and also the infrequency with which autoantibodies characteristic of idiopathic systemic lupus erythematosus are induced. PMID- 3325203 TI - Homogeneous immunoglobulins in the sera of lung carcinoma patients receiving cytotoxic chemotherapy--detection with the use of isoelectric focusing and immunoblotting. AB - Using isoelectric focusing (IEF) with immunoblotting, we have analysed serum immunoglobulins of 15 lung cancer patients on cytotoxic chemotherapy. In five of the patients homogeneous immunoglobulins were found which appeared between 9 and 18 months after beginning of treatment and were monoclonal in two and oligoclonal in three cases. These abnormalities were only partially shown by zonal electrophoresis with immunofixation and not detected by immune electrophoresis. Examination of 10 normal and 10 myeloma sera by the three techniques in parallel confirmed the competence and sensitivity of IEF with immunoblotting in detecting homogeneous immunoglobulins. Thus, this method provides a valuable tool for investigating an abnormal regulation of the immunoglobulin synthesis. PMID- 3325205 TI - Techniques of chorion villus sampling. AB - Whilst randomized studies into the safety of chorionic villus sampling (CVS) are already under way the technique is now offered as an acceptable alternative to amniocentesis in many diagnostic centres. In counselling, the obstetrician can now quote a risk to the pregnancy of 2-4% which, even if the inevitable losses before 16 weeks are excluded, represents probably at least twice the risk of amniocentesis. The evolution of the obstetric procedures has meant that the transcervical approach to CVS has been the most popular to date but there is now increasing interest in transabdominal aspiration as it minimizes the possibility of infection. The two best known transcervical methods are aspiration with a plastic or metal cannula and biopsy with rigid forceps. The majority of aspirations have been performed using the Portex cannula technique. Using this, three centres (Milan, Chicago and Philadelphia) have had experience of over 5000 cases with a failure rate of less than 1% and a minimal fetal loss of 2.2%. However, the proportion of fetal losses may be between 4 and 7% by the time complete obstetric follow-up is available (Brambati et al, 1985). A similar technique has been used with a variety of cannulae. The experience of the first 1000 cases from San Francisco (Hogge et al, 1986) led them to conclude that CVS by this technique was acceptably safe but that continuing investigation was needed before CVS was offered routinely as an alternative to amniocentesis. The only other transcervical technique that is practical for routine use is biopsy with rigid forceps. The failure and fetal loss rates associated with this method are comparable to the aspiration technique. The pioneering work of Hahnemann and his colleague Smidt-Jensen has established transabdominal aspiration as a reliable alternative approach. Its main advantage should be to minimize the risk of infection which is inherent in all transcervical techniques. In addition, it does not need to be confined to 9-11 weeks gestation and thus offers couples the possibility of diagnosis between 12 and 14 weeks rather than waiting for amniocentesis at 16 weeks. The quality and quantity of the sample depends on the size of the needle used and the technique is said to have high patient acceptability. Nevertheless, fetal losses occur following the procedure (1.8 3.2%) and it may not always be successful (failure rate 1.9-4.2%). PMID- 3325204 TI - Detection of anti-mitochondrial antibodies by ELISA and Western-blot techniques and identification by one and two-dimensional gel electrophoresis of M2 target antigens. AB - Seven hundred and eleven sera were simultaneously studied by immunofluorescence (IF), complement fixation test (CFT) and ELISA for the detection of anti mitochondrial antibodies (AMA). One hundred and nineteen of these sera were also studied by Western-blot techniques, while some of them were examined by two dimensional gel electrophoresis so as to identify the polypeptides recognized by M2 antibodies. The results indicated that: (1) ELISA is a more sensitive technique for detecting type M2 AMA (27 scored positive in 27 primary biliary cirrhosis (PBC), as compared to 21/27 by IF and 16/27 by CFT). (2) Although ELISA appeared to be a promising screening method, some false positive results were observed that necessitated a double confirmation of positive sera by another technique. (3) Western-blot experiments with rat mitochondrial purified preparation indicated that sera from AMA type 2 could recognize eight different polypeptides and that most of them identified 63-60, 48, 44, and 35-33 kD polypeptides, whereas the 54 and 27 kD were less frequently recognized. A trypsin treatment of antigens confirmed the enzyme sensitivity of most of these antigens. These results suggested some heterogeneity among M2 AMA, though this series of PBC was not large enough to relate the heterogeneous pattern noticed in Western blot to the clinical and histological patterns observed in PBC. PMID- 3325206 TI - Fetal diagnosis of inborn errors of metabolism. AB - Nearly 4000 different human disorders are supposed or known to be due to a single gene mutation. In about 10%, an early diagnosis is possible by the demonstration of specific abnormalities of metabolites in blood and/or urine, an abnormal structure/function of a particular (enzyme) protein or by the (in)direct demonstration of the gene mutation using DNA analysis. These methods of molecular analysis can often also be used for carrier detection. Early identification of couples at risk of handicapped offspring followed by genetic counselling forms the basis for prevention. Follow-up studies have shown that more than half of the couples at risk of a child with a genetic disease refrain from pregnancy. An important alternative for couples at risk is prenatal monitoring and selective abortion. During the last 10-15 years, the technology of fetal diagnosis of genetic diseases has improved and the number of Mendelian disorders that can be diagnosed in utero has increased to more than 100. In the second-trimester of pregnancy, about two dozen inborn errors of metabolism have been diagnosed by metabolite analysis of amniotic fluid supernatant using gas chromatography-mass spectrometry or electrophoretic methods. About 5000 pregnancies at risk of different types of haemoglobinopathy, haemophilia, alpha-1-antitrypsin deficiency and a few other diseases not expressed in amniotic fluid cells have been investigated by biochemical analysis after fetal blood sampling. The most common approach towards fetal diagnosis of inborn errors of metabolism has been the demonstration of a specific enzyme deficiency in cultured amniotic fluid cells. In this way some 60 different diseases have been diagnosed, usually after 2-4 weeks of cultivation after amniocentesis at 16 weeks gestation. In addition, some 20 other Mendelian disorders have been diagnosed in utero by ultrasonography and non-biochemical analysis of amniotic fluid cells or fetal skin biopsies. The introduction of chorionic villus sampling has offered the possibility of first trimester fetal diagnosis of a large number of Mendelian disorders. The overall diagnostic experience until mid-1986 amounts to about 1500 pregnancies at risk. Some 45 different inborn errors have been diagnosed by enzyme assays directly on chorionic villus homogenate or after incubation with radiolabelled precursors of intact villi followed by chromatography or other types of analysis. In a few instances, cell cultivation for a period of 2-3 weeks is required to establish a reliable biochemical diagnosis. PMID- 3325207 TI - The impact of DNA analysis on fetal diagnosis. AB - There has been rapid progress in mapping disease-specific gene loci to particular chromosomal regions and in cloning the relevant genes or DNA sequences that can act as genetic markers. These advances will have an impact on fetal diagnosis of monogenic disorders for a number of reasons, the most important being the ability to use chorionic villus DNA taken in the first trimester to make a fetal diagnosis, no matter how tissue-specific the gene defect. Diagnosis based on analysis of the protein gene product requires a tissue that is expressing that gene. In a few disorders the mutation within the gene can be detected directly, but more often an approach, termed gene tracking, will be required to predict the genotype of the fetus. This requires blood samples from a few family members and the analysis must be carried out prior to the chorion sampling and ideally before the pregnancy. This initial family study is required to determine whether gene tracking is possible in that particular family. A number of potential problems, both technical and in clinical management, highlight the need for close collaboration between clinical geneticists, molecular geneticists and obstetricians. PMID- 3325208 TI - Diagnosis and management of fetal malformations. PMID- 3325209 TI - Fetal blood sampling. PMID- 3325210 TI - Fetal diagnosis of cystic fibrosis. AB - Two different methods of prenatal diagnosis of CF are currently available. Both are usually only suitable for couples with a 1 in 4 risk of bearing an affected child. The method of choice is first trimester diagnosis on a chorionic villus sample using linked DNA probes. The advantages are: 1. The very high degree of accuracy of diagnosis, 2. The opportunity of first trimester termination of pregnancy when the fetus is affected. The disadvantages are: 1. The need for a blood sample from an index affected child to establish phase, 2. The requirement for early workup of the nuclear family to ascertain informativeness, 3. The chance that some families will be uninformative or only partially informative for available DNA probes. An alternative form of diagnosis is that using microvillar enzyme testing on second trimester amniocentesis samples. The advantages are: 1. It is suitable for all pregnancies with a 1 in 4 risk of CF, 2. No prior workup of the family is required, 3. Assays can be completed within one hour of receipt of the sample. The disadvantages are: 1. The accuracy of diagnosis leaves some scope for error, 2. If termination of pregnancy is indicated this can only be carried out at about 18 or 19 weeks of gestation. PMID- 3325211 TI - Congenital anomalies in twins. PMID- 3325212 TI - Genetic aspects of congenital malformations. AB - Ninety percent of congenital malformations are wholly or partly genetic in aetiology. They may arise from single gene mutations, multifactorial inheritance or chromosomal abnormalities. The single gene malformation syndromes are especially important to identify as they may carry a high recurrence risk. Further understanding of the genetic mechanisms of human malformation may come from high resolution cytogenetics and the recombinant DNA technology. One particularly exciting new development is the sequencing of genes responsible for embryological development in lower animals and finding that homologous gene sequences are also present in man. PMID- 3325213 TI - Prospects for prenatal diagnosis during preimplantation human development. PMID- 3325215 TI - The relationship between antidepressant response and tricyclic antidepressant plasma concentrations. A retrospective analysis of the literature using logistic regression analysis. AB - The relationship between the antidepressant effect of the tricyclic antidepressants and their plasma concentrations was reviewed. Logistic regression was utilised as an analytical tool to facilitate the evaluation. The currently available literature allowed the construction of 4 tricyclic data sets of sufficient size to warrant statistical analysis. Inspection of the distribution of the data and the logistic regression analyses resulted in several conclusions regarding the existence of 'therapeutic windows' for these drugs. Firstly, no relationship between amitriptyline plasma concentrations and therapeutic response was apparent. Secondly, curvilinear relationships were apparent for 2 of the other tricyclic antidepressants studied. The currently recommended therapeutic range of 60 to 150 micrograms/L for nortriptyline was found to be the range most likely to produce a positive antidepressant effect. Desipramine concentrations between 108 and 158 micrograms/L were most commonly associated with beneficial therapeutic responses. Finally, a linear relationship was noted for imipramine in which an imipramine therapeutic plasma concentration threshold of 244 micrograms/L and above was most commonly associated with a beneficial response to the drug. PMID- 3325216 TI - Ciamexon in the low dose streptozotocin induced diabetes of mice. AB - This article is concerned with suppression of the development of diabetes experimentally induced by multiple injections of subdiabetogenic doses of streptozotocin (4 x 45 mg/kg/d) in mice (CD 1 and C57B16). Streptozotocin injections were followed by hyperglycemia and mononuclear cell infiltration of islets (insulitis). Ciamexon is a new immuno-modulating agent with promising effects in experimental models of autoimmune diseases and practically no toxic side effects. When Ciamexon was given before streptozotocin treatment blood glucose levels in the parenteral glucose tolerance test were suppressed in a dose dependent way. 60 days after streptozotocin application the percentage of islets showing insulitis or even necrosis was reduced in the Ciamexon treated group compared to the streptozotocin only group. In contrast, Cyclosporin A had a detrimental effect on diabetes in this model although blood levels were proved to be in the therapeutic range. From these results we conclude that Ciamexon should be tested for its effect in human type I diabetes. PMID- 3325214 TI - Clinical pharmacokinetics and endocrine disorders. Therapeutic implications. AB - Endocrine disorders are common and produce widespread changes in cellular and organ function. Alterations in the sensitivity of patients with thyroid disorders to digoxin, anticoagulants and sedatives have been recognised for many years. Many of the recently documented kinetic alterations in endocrine patients are explicable on the basis of disease-induced changes in hepatic drug metabolism, protein binding and renal function. In hyperthyroidism the rate of absorption of paracetamol, propranolol and oxazepam is increased due to increased gastrointestinal motility. The volume of distribution of propranolol and digoxin is increased and there is decreased binding of both basic and acidic drugs as a consequence of alterations in alpha 1-acid glycoprotein and albumin concentration. The rate of glucuronidation of paracetamol and oxazepam is increased in hyperthyroidism. While oxidative metabolism of antipyrine, propranolol, metoprolol and theophylline is enhanced, the clearance of a number of other agents, including diazepam, warfarin, antithyroid drugs and phenytoin, is unaltered. The systemic clearance of propranolol is enhanced as a consequence of a 50% increase in liver blood flow. The rate of elimination of a number of endogenous substances, including cortisol, thyroid hormones and insulin, also appear to be enhanced. Hyperthyroidism has a variable effect on renal function, with a possible increase in digoxin elimination, but no effect on the clearance of renally excreted beta-blockers, atenolol, sotalol and nadolol. These kinetic changes suggest that individualization and higher than normal dosage of propranolol is necessary to control hyperthyroidism, and in thyrotoxic atrial fibrillation higher doses of digoxin or additional therapy with beta-blockers, or verapamil, may be indicated. The increased sensitivity of thyrotoxic patients to warfarin suggest care with dosage and frequent monitoring of response are warranted. Less information is available concerning hypothyroidism, but there is a general trend for decreased absorption of paracetamol and propranolol. In addition, the volume of distribution of digoxin is reduced, as is renal clearance. Limited studies suggest no alteration in the glucuronidation of oxazepam, but antipyrine clearance appears to be reduced. Steady-state propranolol concentrations are elevated in hypothyroidism and there appears to be a decreased metabolism of thyroid hormones and cortisol. Preliminary information suggests the binding of propranolol is increased. Thus, in the treatment of hypothyroid patients, a lower dosage of propranolol may be required.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325218 TI - Pancreatic B-cell function during normal pregnancy. AB - 24-h urinary C-peptide excretion was studied in 19 healthy normal weight women with normal glucose tolerance, and related to weight gain and skinfold thickness at 12, 20, 30, 36 weeks of gestation and 6-8 weeks post partum. The urinary C peptide values (total nmoles or nmoles per kg body weight) showed a significant and progressive increase with gestation. The average C-peptide value was already at 12 weeks of gestation 4 times higher than under non-pregnant conditions. The urinary C-peptide excretion was neither related to maternal weight, weight gain or skinfold thickness at any of the observation periods during pregnancy, nor to the plasma C-peptide response to an oral glucose load at 32 weeks of gestation. A significant correlation was found between urinary C-peptide excretion and body weight determined post partum (r = 0.54, p less than 0.05). The increment in urinary C-peptide excretions at 12 weeks of gestation was unrelated to body mass, suggesting that insulin resistance is present already at this early stage of normal gestation. PMID- 3325217 TI - Rapid decrease of insulin-specific IgG antibody levels in insulin-dependent patients transferred to semi-synthetic human insulin. AB - A multicenter, open trial was designed to examine the efficacy and safety of semi synthetic human insulin (SSHI; Novolin R and Novolin L, SQUIBB-NOVO) in patients with insulin-dependent diabetes mellitus who were transferred from other commercially-available insulins. Whether such a change in therapy would reduce circulating IgG antibodies to antibovine insulin was also evaluated. A total of 68 males and females, 8-62 yr of age, were maintained on their original insulin therapy for 4 weeks, when both glycosylated hemoglobin and fasting blood glucose were assessed. IgG antibody titers to antibovine insulin were also measured. All patients were then transferred to SSHI for a period of 20 weeks. The same variables were evaluated at Weeks 2, 4, 8, and 20. Mean fasting blood glucose levels rose monotonically from 189-226.3 mg/dl over the course of the 20-week clinical trial. There was a slight but insignificant increase in glycosylated hemoglobin by the end of the test period. The average value for antibovine insulin IgG antibodies decreased from 2.54 mu/ml at baseline to 1.32 mu/ml by the completion of the trial. Significant decreases were first observed 4 weeks after the patients were placed on SSHI therapy. After transfer to SSHI, 43.3% of the patients achieved some improvement in glycemic control and only 16.4% were worse than at baseline. A decrease in weekly hypoglycemic reactions occurred during the course of the SSHI therapy. It appears that SSHI provides safe and effective treatment for insulin-dependent diabetic patients and that its use results in a rapid and significant decrease in insulin antibody formation. PMID- 3325219 TI - Age-related qualitative and quantitative changes in the endocrine pancreas of the LA/N-corpulent rat. AB - Islets of Langerhans in sections from the tail of the pancreas of corpulent LA/N cp rats and lean controls aged 1, 3, 6 and 9 mo were examined by immunocytochemistry and morphometrically using an automatic image analyzer. The corpulent rats had significantly greater islet volumes at all ages, although islet hypertrophy tended to plateau after 6 mo. By 12 mo age the architecture of the islets was disrupted with large islets fused and showing areas of fibrosis and deposits of hemosiderin. The volume density (v/v, %) of islets in the parenchyma was significantly increased at each age step in corpulent rats reaching over 20% at 9 mo, and was greater in corpulent than in lean rats at all ages. In the corpulent rats, B-cell volume density dramatically with age and at all ages was significantly greater in corpulent than in lean rats. A-cell volume density was significantly greater in the corpulent rats than in lean rats at 1 and 9 mo. The mean B:A cell ratio was greater in corpulent than in lean rats at 3, 6 and 9 mo. There were more D cells per islet in corpulent than in lean rats up to 9 mo. These changes in cell populations were paralleled by qualitative changes in islet morphology and cellular topography such as increasingly irregular islet shape in corpulent animals and by variations in plasma levels of insulin and glucagon. In this strain of rats, obesity is associated with major changes in pancreatic morphology and this correlates strongly with the susceptibility of the strain to atherosclerosis. PMID- 3325220 TI - Multiple insulin injections using a pen injector versus insulin pump treatment in young diabetic patients. AB - Continuous subcutaneous insulin infusion (CSII) of 6 months duration was compared with 6 months of multiple insulin injections (MII) using a pen injector (NovoPen) in a prospective cross-over study with 20 young insulin dependent diabetics by evaluating metabolic control, insulin requirements and patient acceptability. Following both intensified regimens (CSII/MII) serum fructosamine declined significantly from 4.1 +/- 0.7 to 3.4 +/- 0.5 mmol/l and 3.6 +/- 0.7 mmol/l respectively (normal range: 2.2 +/- 0.2 mmol/l). When comparing CSII and MII no significant differences could be demonstrated in mean blood glucose (MBG), fasting plasma ketone bodies, fasting plasma free fatty acids (FFA), fasting plasma human growth hormone (HGH), fasting plasma glucagon or serum fructosamine. Mean insulin requirement was 11.4% higher during MII and glucose instability- demonstrated by the M-values and by the frequency of blood glucose values below 4 mmol/l--was significantly (p less than 0.02) higher during the MII treatment. All of the patients reported a better well-being on both treatment regimens and none of them wanted to go back to conventional therapy (CT). In conclusion, on a long term basis both regimens result in identical metabolic control, but due to physical discomfort during pump treatment, the insulin pen injector was preferred by the majority (80%) of the patients. PMID- 3325221 TI - Primin as the source of sea-urchin hypersensitivity? PMID- 3325223 TI - Bicentennial of the birth of J. E. Purkyne. PMID- 3325222 TI - Contact dermatitis to sesquiterpene lactones in Inula viscosa Aiton. PMID- 3325224 TI - Acute myocardial infarction after renal transplantation. AB - The authors evaluated the incidence of acute myocardial infarction (AMI) in a group of 355 renal graft recipients operated on at the Institute for Clinical and Experimental Medicine between 1976 and 1984. AMI was diagnosed in 12 (3%), mostly male, patients. The age of AMI survivors was higher on the average (47.5 years) than that of other renal graft recipients whose mean age was 37 years. Another difference was a higher proportion of patients aged 50 and more. Compared with a selected control group of transplant recipients (n = 97) of corresponding age and follow-up period, the incidence of AMI rose to 9%. The prognosis of renal graft recipients with AMI was a favourable one, only in two cases was AMI and its complications the immediate cause of death. Cumulative doses of immunosuppressive drugs (prednisone, azathioprine, and methylprednisolone) were higher in AMI patients. The difference was not statistically significant in view of the low number of patients. The observed differences should be taken into account when designing corticosteroid dosing schedules in elderly graft recipients. PMID- 3325225 TI - Mechanism and stereoelectronic effects in the lysozyme reaction. AB - Lysozyme occupies a special place in the history of enzymology as the first enzyme to have its three-dimensional crystal structure elucidated by Phillips and co-workers in 1965. The crystallography, and much biochemical work, revealed three factors likely to be important for the mechanism of action: catalysis by the carboxyl group of Glu-35, catalysis by the ionized carboxyl group of Asp-52, and the conformation of the bound polysaccharide substrate. The work of the last 20 years has defined likely roles for the catalytic groups, but discussion of the conformational question came to a head only very recently with the suggestion that the fundamental stereoelectronic requirements of the glycoside-cleavage reaction might be decisive. Recent work on all three interlinked factors are reviewed. PMID- 3325226 TI - Mechanism of methylmercury cytotoxicity. AB - Although a large number of epidemiological, clinical, and pathological studies on methylmercury intoxication have been published, these investigations have not been able to elucidate the detailed mechanisms by which the metal alkyl causes a wide variety of biological dysfunctions. Thus, the cultured cells which are free from the influence of whole body complexities, such as absorption, distribution, metabolism, etc., which complicate the interpretation of in vivo experimental results, attract the attention of many scientists who are interested in clarifying the mode of toxic action of methylmercury. The aim of this article is to review the recent studies on the toxicity of methylmercury at the cellular level and to outline the mechanisms which have been proposed to be responsible for cell injuries. PMID- 3325227 TI - The toxicology of bromide ion. AB - Inorganic bromide is widely distributed in nature. Its natural physiological role in animal life is unknown. More than a century ago bromide was introduced in medicine as an antiepileptic drug. Nowadays, man is primarily exposed to bromide via food as the result of use of bromide-containing fumigants in intensive horticulture and in the treatment of food stocks. In this review exposure of man to bromide is described, and the pharmacological and toxicological effects of bromide ion are discussed. PMID- 3325228 TI - Indirect food additive migration from polymeric food packaging materials. AB - Many foods contact polymeric packaging materials which contain residues of the polymerization process or additives employed to facilitate processing. The extent of migration of such materials from the packaging to foods is the focus of the present article. A major experimental program using eight polymer-migrant systems is described. Migration was measured to food-simulating liquids (FSL) and to foods. Accelerated tests were conducted with FSL under FDA guidelines conditions so as to develop correlations between such data and those found using foods under normal storage temperatures and shelf lives. In the majority of tests, the migration was found to be approximately proportional to the square root of time, to increase significantly with a rise in temperature, and to be proportional to the initial concentration of migrant in the polymer. Stirring in the FSL or food phase was generally not important except for the system involving dioctyl adipate migrating from polyvinyl chloride film. In some instances, after a period of time, migration rates became very low, and this effect was attributed to saturating the FSL or food phase with migrant. The foods comprised a variety of types, including liquid, semisolid, solid, and dry; both oily and aqueous foods were included. The physical steps involved in migration include the diffusion of the migrant from the interior of the film to the surface, where it can dissolve in the external FSL or food phase. The nature of the FSL or food is shown to be very important in that components can penetrate the polymer and dramatically increase migration rates. Consistent with the FDA guidelines in effect at the time of this study, testing was performed with five FSL (water, 3% acetic acid, 8% and 50% ethanol, and n-heptane) at 49 degrees C. Detailed comparisons were made between the migrations to foods and to FSL; following are the more relevant conclusions. (1) Three percent acetic acid showed no advantage over water as a food simulant even in those cases where the food could be considered acidic in nature. (2) Water, when used as an FSL at 49 degrees C for 5 days, overestimated migration in aqueous foods in about 75% of the cases. In some instances, however, the water phase became saturated with migrant. In other situations, this test protocol underpredicted migration--especially in those cases where there were components in the food that were able to penetrate into the polymer and enhance migration (such as orange juice).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325229 TI - Isosorbide-5-mononitrate and isosorbide dinitrate retard in the treatment of coronary heart disease: a multi-centre study. AB - A multi-centre study was carried out in 200 coronary patients to compare the efficacy and tolerance of isosorbide dinitrate retard (40 mg) and isosorbide-5 mononitrate (20 mg) with regard to the frequency of anginal attacks and consumption of sub-lingual (short acting) nitrates. After receiving treatment for 2 weeks with isosorbide dinitrate retard at a dosage of 2 or 3 tablets per day, only those patients continued the study who had a weekly average of 4 or more anginal attacks during this basal period. The selected patients were divided in 4 groups of 50 patients and received treatment for a further 4 weeks with either isosorbide dinitrate retard at a dosage of 2 tablets (Group D2) or 3 tablets (D3) per day or isosorbide-5-mononitrate at a dosage of 2 tablets (Group M2) or 3 tablets (Group M3) per day. A progressive improvement in symptoms was seen at the end of 2 and 4 weeks with both drugs. The greater therapeutic benefits were obtained in patients in Group M2; the greater difference was observed between Group M2 and D2 (p less than 0.01) and there were also significant differences (p less than 0.05) between Groups M2 and D3 and between Groups M3 and D3. Analysis of the results showed that the more frequently angina attacks had occurred during the basal period, the greater was therapeutic benefit obtained with isosorbide-5 mononitrate compared to isosorbide dinitrate retard at the end of the study. Heart rate at the end of the study showed a slight tendency to increase over initial levels in all groups. In contrast, systolic blood pressure decreased very significantly in all groups (p less than 0.001). Diastolic blood pressure also decreased in all groups but only to a highly significant degree in patients treated with isosorbide-5-mononitrate (p less than 0.001) and the two sub-groups M2 and M3 (p less than 0.005). In patients treated with isosorbide dinitrate retard, the reduction in diastolic pressure was only statistically significant when the 100 patients in the group were considered as a whole (p less than 0.05), while this was not the case for the two sub-groups D2 and D3. The most frequent side-effect was headache, which improved gradually. During treatment there was a progressive dissociation between reduction in the intensity and frequency of this adverse effect and the increasing anti-anginal action of the nitrates. PMID- 3325230 TI - A clinical trial of glycosaminoglycan-peptide complex ('Rumalon') in patients with osteoarthritis of the knee. AB - A clinical trial was undertaken in 50 patients with osteoarthritis of the knee to assess the therapeutic value of glycosaminoglycan-peptide complex in treatment. The first year consisted of a randomized, double-blind, placebo-controlled, parallel-group trial (25 patients in each group), after which all patients received active treatment for a further 2 years. Treatment consisted of three 8 week courses in the first year and 2 such courses per year in subsequent years, each consisting of 2 ml intramuscular injections given 3 times per week. Patients were permitted to continue taking anti-inflammatory drugs and to receive physiotherapy during the trial period. At the end of the first year of the trial (double-blind phase), there were no significant differences between the two treatment groups. However, after the second year, those patients who had received glycosaminoglycan-peptide complex for 2 years had significantly greater improvements in night pain and rest pain than did those who had received active treatment for only 1 year. At the end of 3 years (when half the patients had received active treatment for 2 years and half for 3 years), there were significant overall improvements in relation to rest pain, pain on walking and morning stiffness, but not in respect to night pain, pain on standing or climbing stairs. At the same time, improvements were seen in radiological severity of disease (assessed double-blind) in 16% of patients, with 'no change' in 74% and deterioration in 10%, these figures being considerably better than might be expected with conventional therapy. Glycosaminoglycan-peptide complex was extremely well tolerated. PMID- 3325232 TI - Determinants of regional myocardial oxygen supply in the left ventricle. An experimental study in the in situ working canine heart. AB - The main factors that regulate myocardial oxygen supply include the 1. coronary blood flow controlling the volume flow fraction of red cells, 2. the oxygen carrying capacity of capillary blood dependent on the red cell volume fraction occupying the capillaries, and 3. the density of perfused capillaries affecting the capillary diffusion capacity and the diffusion distance in the tissue. Differences exist between the inner and outer layers of the left ventricle that include differences of systolic and possibly diastolic tissue stresses and oxygen consumption. The highest values were observed in the vicinity of the left ventricular cavity. The regional differences of myocardial oxygenation were studied in anaesthetized open-chest dogs by measuring the myocardial perfusion rate, the microvascular hematocrit, the PS-product of 51Cr-EDTA, and the microvascular blood volume across the left ventricular wall in the heart working in situ. Gradients of blood flow rates were present with the highest flow in deep myocardial layers. Maximally increasing the coronary blood flow at normal perfusion pressure and metabolic load did not change the distribution of blood flow between subendocardial and subepicardial layers. Distal to a coronary stenosis, blood flow was markedly reduced and redistributed away from the subendocardial layers, indicating a relatively severe decrease of fractional red cell flow to the left ventricular myocardium. The microvascular dynamic hematocrit, i.e. the volume fraction of red cells, was evenly distributed across the left ventricular wall, but consistently reduced to 75 per cent of great vessel hematocrit. The maximal increase of coronary blood flow provoked a further reduction of microvascular hematocrit due to a decrease of the red cell volume, possibly by shunt flow of red cells through low resistance vessels of capillary size. At restricted coronary inflow, the microvascular hematocrit was decreased with a redistribution of red cells away from deep myocardial layers. Extern compression of microvessels by the tissue pressure, phase-separation between red cells and plasma at microvascular bifurcations, or decrease of the red cell fluidity may all contribute to this change. Reduction both of microvascular red cell flow fraction and the hematocrit diminishes the red cell flux within capillaries and decreases the ability of blood to deliver oxygen to the tissue, and more so in the subendocardial layers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325231 TI - Fragile X syndrome. AB - The fragile X syndrome is the most common inherited form of mental retardation known. Its phenotype includes large or prominent ears, macroorchidism, and characteristic behavioral problems. It has attracted the interest of cytogeneticists and molecular biologists because of its characteristic fragile site on the X chromosome. It has puzzled geneticists because of its unusual inheritance pattern involving nonpenetrant males. This syndrome has also spearheaded an appreciation of cytogenetic abnormalities in the etiology of all degrees of developmental delay. PMID- 3325233 TI - Anti asthmatic effects and pharmacokinetics of enprofylline--a new xanthine derivate. PMID- 3325234 TI - Kinesiology of the knee joint. An experimental investigation of the ligamentous and capsular restraints preventing knee instability. AB - The purpose of this study was to elucidate the function of the ligamentous and posterior capsular structures of the knee joint and the types of instability that may be caused by lesions to these structures. Despite the use of complicated technical appliances and the defined, uniform conditions, the investigators in measuring the mobility in the knee joint have usually arrived at divergent results. Often, the manner of measuring the various movements has not been mentioned, or the moment or force applied to the knee joint were not well defined, or else the instability was recorded at only a few positions during the extension-flexion movement of the knee. A measuring apparatus was devised which allows continuous registration, accurately, and in a reproducible manner, of the valgus-varus, axial rotatory, and translatory instability in the extension flexion movement of the knee during application of a well-defined, constant moment or force to the knee joint. A lever, fitted with strain gauges and connected to three potentiometers, was fixed to the tibia. The lever was moved manually in a way so that during a "circumduction" of the lever, the moment was constant in the valgus, varus, internal or external axial rotation direction. Likewise, the anteriorly or posteriorly directed force was constant. Anterior posterior tibial displacement was measured by two sliding potentiometers. By means of a computer the resulting movement could be plotted in the form of mobility patterns. Patterns were plotted partly with intact ligaments and partly after isolated and various combinations of transection of the collateral ligaments, the posterior capsule, the cruciate ligaments, and the popliteal tendon. A total of 115 preparations were investigated in this manner. PMID- 3325235 TI - Preferential DNA repair in active genes. AB - We have demonstrated that essential genes in rodent cells and in normal human cells are preferentially repaired after UV damage. In rodent cells, some genes are repaired much more efficiently than the bulk of the genome. This may explain the long standing paradox that their overall genome repair is low, but their UV survival is as high as for proficiently repairing human cells. Rodent cells appear to repair efficiently only genomic regions of vital importance. In normal human cells, we have found that genes are repaired faster than the bulk of the genome, but eventually (after 24 hrs) all genomic regions are proficiently repaired. The demonstration of preferential DNA repair mandates caution in interpreting correlations between overall DNA repair capacity and other biological parameters. Changes in preferential DNA repair could have profound effects on such parameters without noticeably altering overall genome repair levels since the vital regions only constitute less than 1% of the genome. We have correlated overall genome repair, repair in the DHFR gene, and UV resistance for three different cell lines: CHO, XPC and normal human. The results further suggest that determinations of DNA repair in specific genomic sequences may be more important than overall DNA repair measurements for correlations to other biological end points such as resistance to UV damage. Although DNA repair heterogeneity has been demonstrated in XPC, we have found that the preferentially repaired regions in these cells do not include the essential DHFR gene. DNA repair may normally be regulated over the genome in a similar manner to that for transcription, and we propose that this regulation is deficient in the human DNA repair deficient syndrome XPC. We have also analyzed the genomic fine structure of DNA repair in and around the DHFR gene in CHO cells. We find a region of preferential DNA repair of approximately 60-80 kb in length with maximal DNA repair efficiency at the 5' end of the gene and in its 5' flanking sequences. This size corresponds very well with proposed and measured lengths for loops or domains of higher order structure in chromatin, and suggests that DNA repair efficiency in genomic regions might reflect aspects of local chromatin structure, and thus provide us with a probe for the detection of chromatin structural changes. We have found considerable differences in the repair efficiency of different genes within the same cell.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325236 TI - Septicaemia in childhood malignancy. AB - In this study, 44 episodes of septicaemia occurred in 32 children over a 5 1/2 year period. The mean number of hospitalised children with malignant diseases was 88 a year. During the study period, there were a total of 1,818 admissions. The mean age was 7 years (2 months to 16 years) with a male predilection (66%). The majority of septicaemias occurred in children with leukaemia (52%), but their mortality was lower than in children with malignant lymphoma. No children with solid tumours died in connection with septicaemia. All deaths in connection with septicaemia occurred in children with less than 0.5 X 10(9) granulocytes per litre, and none of these children were in remission. Twelve different bacterial species were isolated with Staphylococcus aureus, coagulase negative staphylococci, and Escherichia coli, accounting for 75% of these episodes. The mortality was 14%, most often (67%) in connection with septicaemia caused by Gram negative organisms. It is emphasised that the type of infecting microorganisms and the outcome of the infections must be recorded regularly and the antibiotic regimen adjusted accordingly. PMID- 3325237 TI - Volvulus of the cecum. AB - Twenty-six cases are reported of ileo-cecal volvulus admitted to three community hospitals over a period of six years. The operative management of ileo-cecal volvulus is discussed. Based on the results and review of the literature the authors recommend a right hemicolectomy in the presence of gangrene or perforation, in other cases a cecopexia with fixation in combination with intestinal tube decompression when needed. PMID- 3325238 TI - Negative fetal effects of treatment of hypertension in pregnancy. PMID- 3325239 TI - [AIDS from the viewpoint of the surgeon]. PMID- 3325240 TI - [Semirigid plate osteosyntheses using absorbable polymers as temporary implants. II. Animal experiment studies]. AB - Polylactide-l test rods showed an initial stability of 130 N/mm2 in the three point bending test; the stability decreased after implantation in the dorsal muscle of the rat within 5 weeks to about half the initial value. The copolymer materials showed less initial strength, and the stability decreased under the same conditions much earlier. All materials showed good tissue compatibility. After a transverse section of the beagle radius was stabilized with plates and screws out of polylactide-l, a delayed bony union with callus formation was observed. PMID- 3325241 TI - [Cancer in situ of the gallbladder with an anomaly of the choledochopancreatic junction associated with left unilobar Caroli's disease]. PMID- 3325242 TI - [Modalities of surgical treatment of gastroesophageal reflux and technical deductions: cardioplasty]. PMID- 3325243 TI - [Imaging technics in injuries of the spleen in children. Its significance for indications of conservative treatment]. PMID- 3325244 TI - [Hepatic transplantation in alveolar echinococcosis. 3 attempts]. PMID- 3325245 TI - [Beta 2-microglobulin in IgA nephropathy]. PMID- 3325246 TI - [Thrombolytic therapy: a new method for the treatment of acute myocardial infarction]. PMID- 3325247 TI - [Calcium-channel blockers and the digestive system]. PMID- 3325248 TI - [Os4O4 reacts primarily with -10 and -35 sites of Escherichia coli lacUV5 promoter]. PMID- 3325249 TI - [Preliminary study on plasma 6-keto-prostaglandin F1 alpha levels before and after induction by furosemide in hypertensive patients]. PMID- 3325250 TI - [Clinical significance of using captopril compounds treating primary hypertension]. PMID- 3325251 TI - [Electrophysiologic characteristics of the accessory bundle in W-P-W patients and its clinical significance]. PMID- 3325252 TI - [Treatment of mild hypertension]. PMID- 3325253 TI - Why do controlled-drinking outcomes vary by investigator, by country and by era? Cultural conceptions of release and remission in alcoholism. AB - Variations in the reported rates of controlled drinking by former alcoholics are notable, at times startling. Reports of such outcomes (which in some cases involved a large percentage of subjects) were common for a brief period ending in the mid- to late 1970s. By the early 1980s, a consensus had emerged in the United States that severely alcoholic subjects and patients could not resume moderate drinking. Yet--at a point in the mid-1980s when the rejection of the possibility of a return to controlled drinking appeared to be unanimous--a new burst of studies reported resumption of controlled drinking was quite plausible and did not depend on the initial severity of alcoholics' drinking problems. Variations in controlled-drinking outcomes--and in views about the possibility of such outcomes--involve changes in the scientific climate and differences in individual and cultural outlooks. These cultural factors have clinical implications as well as contributing to the power of scientific models of recovery from alcoholism. PMID- 3325254 TI - Development of resistance to ofloxacin. AB - As a member of the 4-quinolone group of antibacterial agents, ofloxacin shares the almost unique feature of being exempt from plasmid-borne resistance in either Gram-negative or Gram-positive bacteria. In the light of this feature, the development of resistance mediated through chromosomal mutation has been carefully studied, particularly the processes of mutation which confer resistance to levels of ofloxacin approaching those obtained at the site of infection after oral administration. With Escherichia coli strain KL16 being used as a model system, the genetics of the development of resistance to ofloxacin at least 2 mg/L have been studied. In common with many in vitro studies of the development of resistance to the newer 4-quinolones, it has been observed that the mutation frequency was extremely low (in the range 1 X 10(-10) to 1 X 10(-12) with bacteria grown under routine laboratory conditions. The resultant organisms were very slow growing, temperature sensitive and apparently auxotrophic. The mutation(s) were, however, very unstable and the mutants readily reverted to ofloxacin sensitivity in the absence of selection with ofloxacin. Subsequent studies of spontaneous mutation under growth conditions more closely related to the in vivo situation in the lumen of the gut, with limitation of oxygen supply, showed that mutation frequencies were in the order of 1 X 10(-8). Mutants obtained under these conditions displayed the same phenotype as found previously and were equally unstable. Examination of the physiology of the ofloxacin resistant mutants has shown that they display significant metabolic defects with regard to being able to cope with environmental fluctuations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325255 TI - Single doses of ofloxacin in uncomplicated gonorrhoea. AB - The clinical efficacies of 2 different single-dose oral treatments of ofloxacin were evaluated in a double-blind, randomised study of 60 males with gonococcal urethritis. 30 patients received a single dose of ofloxacin 100mg and 30 received a single dose of ofloxacin 200mg. The minimal inhibitory concentrations of ofloxacin against all isolates were less than or equal to 0.25 mg/L. Neisseria gonorrhoeae was eradicated from all 50 patients evaluated and clinical cure was achieved in 84%. In total, 8 patients developed post-gonococcal urethritis, although there was a significantly (p less than 0.05) lower rate of post gonococcal urethritis in the group treated with ofloxacin 200mg. In conclusion, a single oral dose of ofloxacin 100mg could be an alternative treatment for uncomplicated gonorrhoea. PMID- 3325256 TI - Antimicrobial prophylaxis in immunocompromised patients. AB - The results of a randomised, prospective trial to investigate the efficacy of prophylactic treatment with ofloxacin during granulocytopenia after cytostatic treatment are presented. 42 patients with metastasised testicular germ-cell tumours entered the study. Cytostatic treatment consisted of at least 4 courses, 2 of which were succeeded by prophylactic treatment with ofloxacin. Three patients undergoing prophylactic treatment developed fever. Fever occurred in 16 patients during control phases (no ofloxacin prophylaxis) of cytostatic treatment. Seven of the 19 infections could be documented microbiologically. No side effects that related to ofloxacin were noted. In conclusion, ofloxacin was highly effective in the prevention of infection and, therefore, should be given prophylactically to patients with granulocytopenia. PMID- 3325257 TI - Side effects of ofloxacin in clinical trials and in postmarketing surveillance. AB - Data derived from clinical trials of ofloxacin in 15,962 patients show that the incidence rate of adverse drug events was 4.27 per 100 patients. Symptoms were generally mild and related to the gastrointestinal tract, nervous system or hypersensitivity reactions in rank order. On the other hand, spontaneous reports obtained during postmarketing surveillance involving 1.5 million patients showed that the most frequent adverse drug events were related to the nervous system; next in order of frequency were hypersensitivity reactions and gastrointestinal symptoms. A comparison of the data obtained from clinical trials and postmarketing surveillance revealed no change in the favourable overall benefit:risk ratio of ofloxacin. Possible reasons for the different patterns of adverse drug events are discussed. PMID- 3325258 TI - Overview of toxicological studies. AB - Ofloxacin was tested in various toxicological test systems. In common with other 4-quinolone derivatives, ofloxacin caused erosions and eruption of blisters in articular cartilage of immature animals. Such effects have not occurred in adults, and monkeys have tolerated ofloxacin up to 40 mg/kg/day for up to 12 months. Administration of various doses of ofloxacin to rats, dogs and monkeys for 4 weeks or up to 12 months did not cause anaemia. Ofloxacin did not impair male fertility. Pefloxacin, in contrast, caused azoospermia and testicular damage in dogs, and enoxacin caused testicular atrophy in rats and reduced spermatogenesis in dogs. In tests for cataractogenesis, ofloxacin was inactive, and adverse hepatic and renal effects occurred only after doses which were greater than the equivalent therapeutic maximum. Mutagenicity studies were negative. Only a recently conducted unscheduled deoxyribonucleic acid synthesis (UDS) test showed some effects, again at therapeutically non-significant concentrations. PMID- 3325259 TI - The use of quinolones in respiratory tract infections. AB - In a prospective (and continuing) trial, a total of 271 patients with acute purulent exacerbations of chronic respiratory disease (bacteriologically confirmed) were treated with various new oral quinolones including enoxacin (26), pefloxacin (50), ciprofloxacin (80) and ofloxacin (115). Various therapeutic schedules were employed, with differing drug dosages, frequencies of administration and durations of treatment. All patients were investigated microbiologically during and immediately after treatment and after 7 days of follow-up. The best clinical results were noted after ofloxacin 800 mg once daily for 7 days, which showed excellent gastrointestinal absorption and rapid penetration through to the sputum. Some of the treatment failures with enoxacin and pefloxacin could be ascribed to the development of resistance during treatment, rises in minimal inhibitory concentrations (MICs) being noted with Streptococcus pneumoniae and Pseudomonas aeruginosa. PMID- 3325260 TI - Clinical efficacy of ofloxacin in lower respiratory tract infections. A multicentre study. AB - A multicentre clinical trial was carried out to determine the activity and tolerability of ofloxacin in the treatment of lower respiratory tract infections. 667 patients were randomly allocated to 1 of 3 different twice daily dosage regimens: 400 mg (245 patients), 600 mg (211) or 800 mg (211). The mean duration of treatment was 8.77 +/- 2.62 days. Satisfactory overall clinical results (i.e. cured or improved) were obtained in 612 of 667 patients (91.8%). Eradication of pathogens was achieved for 279 of 354 isolated strains (78.8%). Side effects were observed in 31 patients and consisted of gastrointestinal disturbance (22), skin rash (1), neurological disturbance (3) and others (5). No significant alteration of haematological parameters was reported. PMID- 3325261 TI - Ofloxacin in respiratory tract infection. A review of the results of clinical trials in Japan. AB - An open clinical study of ofloxacin in respiratory tract infections was conducted with patients receiving daily doses of ofloxacin 300 mg, 400 mg or 600 mg. The duration of treatment was 6 to 14 days for 70% of the patients. Ofloxacin was effective in 668 of 828 patients analysed (80.7%). Of 293 patients with upper respiratory infections, the efficacy rate was 85.3%. In 535 cases with lower respiratory infections, ofloxacin was effective in 78.1%. It is noteworthy that a 70% efficacy rate was obtained in 80 cases with intractable chronic diffuse panbronchiolitis primarily associated with Pseudomonas aeruginosa. There was no difference in the efficacy rate among various daily doses or severity of infections. In lower respiratory infections the bacterial eradication rate was 80.9% for Gram-positive aerobes (including 80% for Staphylococcus aureus and 76.5% for Streptococcus pneumoniae) and 72.1% for Gram-negative aerobes (including 92.6% for Klebsiella pneumoniae, 32.3% for P. aeruginosa and 97.1% for Haemophilus influenzae). Although there were no serious cases, adverse reactions were noted in 46 of 843 patients (5.5%): 38 cases (4.5%) of gastrointestinal tract reactions (nausea, vomiting, heartburn, etc.), 4 cases (0.5%) of hypersensitivity (e.g. eruption) and 19 (2.3%) of central nervous system effects (e.g. dizziness). Abnormal changes in laboratory findings included elevations of AST (1.2%) and ALT (1.5%) and an increase in the eosinophil count (1.7%). PMID- 3325262 TI - Ruptured tubal pregnancy following tubal sterilization. PMID- 3325263 TI - [Pancreatogastric or jejunal anastomosis following cephalic duodenopancreatectomy -an assessment following animal experiment and clinical studies]. AB - After partial duodenopancreatectomy the authors performed a pancreatogastrostomy with splinting the anastomosis. This method has some advantages vice versa the pancreatojejunostomy. Experiments with animals show that the beneficial effects of pancreatogastral-and pancreatojejunal anastomoses are of limited duration. PMID- 3325264 TI - [Simulation of intestinal microbial overgrowth by continuous culture]. AB - By the aid of continuous flow culture of microbial populations it is possible to answer specific micro_ecological questions even under anaerobic conditions. We present some findings from a continuous flow model of human duodenal juice with microbial overgrowth. Germ counts and species were reproducible in a steady state over several days. Metabolic activity was very high. For example, this model allows the in vitro study of therapeutic possibilities against overgrowth syndrome, microbial fermentation of food, metabolism of drugs and the growth of microorganisms on surfaces in gastrointestinal tract. PMID- 3325265 TI - [Chromosome aberrations and cellular antigens]. AB - A possible role of chromosomal abnormalities in activation of cellular oncogenes is discussed. Data about the types of chromosomal aberrations characteristic of tumours and of expression of oncogenes localized in aberrant chromosomes are compared. For some oncogenes (c-myc, c-myb, c-abl, c-fes, c-fms) a more or less distinct correlation is observed between certain types of chromosomal abnormalities and increase of oncogene expression. On the contrary, one cannot observe such correlation for other group of oncogenes (c-fos, c-ets, c-mos, c-erb A-1, c-sis, c-src). Chromosomal aberrations are probably one of the mechanisms of cellular oncogene activation during the carcinogenesis. PMID- 3325267 TI - [Molecular-genetic aspects of drug therapy of malignant tumors]. AB - State and prospects of the drug cancer therapy are examined in the light of achievements of modern molecular oncology. Special attention is paid to the molecular genetic analysis of the appearance of individual and multiple cellular drug resistance in connection with amplification of definite genes as well as oncogenes. The idea about the possible role of oncogene activation as a universal cell reaction in response to an injury of environmental factors is advanced. It concerns both oncogenesis and induction of cancer cell drug resistance. PMID- 3325266 TI - [Molecular and cellular mechanisms of the induction of differentiation of tumor cells]. AB - Recent data on the mechanism of animal and human tumour cell differentiation induced by different natural and synthetic agents, including antitumour drugs are reviewed. The central role of plasma membranes of the tumour cells and their receptor patterns in the commitment and terminal differentiation of cells is emphasized. Development of a new approach to the cancer therapy based on the combination of tumour cell differentiation induction and cytotoxic effects is discussed. PMID- 3325268 TI - [Antilymphocytic humoral autoimmune response of mice with developing Rauscher leukemia directed against group-specific retrovirus antigens]. AB - The methods of indirect membrane immunofluorescence, immunoenzyme analysis, complement-dependent cytotoxicity and sorption tests were used to demonstrate two types of humoral antilymphocytic autoimmune reactions at the early stage of the Rauscher leukemia in mice of BALB/c, BDF1 and C57B1/6 strains. The first one is directed against group-specific oncoviral antigens (p30, p15) expressed on the lymphocyte membrane of both intact mice and of those with leukemia, the second one is virus-independent and possesses strain specificity. PMID- 3325269 TI - Foreign bodies of the external auditory canal. AB - Most adult patients who have a FB lodged in the EAC will have obvious and uncomplicated presentations; however, the emergency physician must be aware that unusual presentations do exist in adults, and that children frequently do not present with a straightforward history. To date there have not been any controlled studies to help guide the emergency physician in optimal approach to the removal of a FB from the EAC. Currently each clinician must turn to those techniques with which the patient is comfortable and has found successful. Several approaches and instruments are available for removal, including irrigation, suction, forceps extraction, or combinations of these. If the presentation is complicated or attempts at controlled extraction unsuccessful, it is best to refer the patient. PMID- 3325271 TI - Emergency department approach to vertigo. AB - The patient presenting to the Emergency Department with the complaint of "dizziness" is one of the most common as well as most challenging problems confronting the emergency physician today. Because many of these patients are seeking medical help for the first time, it is imperative to have a solid knowledge base of the multiple potential areas capable of producing this symptom. This article is a review of these problems and their specific symptoms. PMID- 3325270 TI - Approach to decreased hearing. AB - This article is designed to review proper procedure by an emergency or primary care physician when evaluating a patient with decreased hearing. It will cover the anatomy and physiology of hearing, as well as the evaluation and initial management of conductive and sensorineural hearing loss. PMID- 3325272 TI - Ear infections. AB - Infections of the ear are among the most frequent causes for patients to seek care in the ED. Although most infections are fairly simple to diagnose and treat, the anatomic complexity of the ear, its shared innervation with other body structures, its proximity to other body systems, and the risk of serious complications necessitate an orderly approach to the care of these problems. This article outlines an approach to the history, physical examination, diagnosis, and management of these infections. Adherence to such an approach should maximize the likelihood of attaining relief and obliteration of pain, prevention of acute and chronic sequelae, and ultimately, patient satisfaction. PMID- 3325273 TI - Ear trauma. AB - Ear trauma, a common problem in emergency medicine is discussed in this review. Although injuries of the ear are not life threatening, they may account for significant morbidity. Patients may experience severe pain, hearing loss, tinnitus, or vertigo. Poor healing of injuries to the external ear may result in a cosmetic deformity as well. Ear trauma may occur secondary to a number of mechanisms, including loud noises, penetrating or blunt trauma, blast injury, chemical exposure, and thermal injury. PMID- 3325274 TI - Removal of foreign bodies of the nose. AB - Nasal foreign bodies are commonly encountered in the emergency department, particularly among children and mentally retarded patients. The diagnosis should be entertained in any patient who presents with a persistent unilateral nasal discharge. Nasal foreign bodies are either inanimate or, less commonly, animate objects. Successful diagnosis and treatment of nasal foreign bodies depends on a careful examination of the nasal cavity. Because of the difficulty in extracting nasal foreign bodies and the lack of cooperation among these patients, general anesthesia should be considered if there is any question concerning the adequacy of nasal examination. PMID- 3325275 TI - Esophageal foreign bodies. AB - Over 80 per cent of ingested foreign bodies pass through the gastrointestinal tract without incident. Sharp (bones, pins, needles, wire) or long (greater than 6.5 cm) foreign bodies are most commonly implicated in perforation. Food boluses are most common in obstruction seen in adult patients and associated esophageal pathology is common in patients aged 60 years and older. Adults with nonfood foreign bodies have a high incidence of psychiatric, social, or chemical derangements. Pediatric patients most commonly ingest coins. Ingestions tend to occur during nonschool months or in high-risk situations, and repeat ingestions are not uncommon. Fatalities and other major complications are linked to type of foreign body, location, and duration of the impaction. Deaths have also occurred with endoscopic and enzymatic modalities of treatment. Glucagon and Foley catheter removal are safe techniques in selected patients, provided resuscitative skill and equipment are available. Based on these data, an algorithmic approach to the management of esophageal foreign bodies by the emergency physician is recommended (Table 5). PMID- 3325276 TI - An approach to throat complaints. Foreign body sensation, difficulty swallowing, and hoarseness. AB - There is a great deal of clinical overlap in patients with throat complaints. Foreign body sensation, difficulty in swallowing, and hoarseness may all stem from one entity or may be totally unrelated. First and foremost, always protect the airway. Thereafter, a thorough history, combined with a directed physical examination and radiologic studies, will provide a concise differential diagnosis. Once the diagnosis is formulated, treatment may take place in the Emergency Department or the patient may be referred to the appropriate specialist for definitive diagnosis or treatment. PMID- 3325277 TI - Approach to acute pharyngitis. AB - The evaluation of the patient with a "sore throat" is deceptively complex. The clinician must first assess the potential for airway compromise. Specific risk factors, reviewed in this article, should be considered, including the presence of a pharyngeal membrane, immunocompromise, potential gonococcal exposure, and prior rheumatic fever. PMID- 3325278 TI - Adenitis, adenopathy, and abscesses of the head and neck. AB - The emergency clinician will continue to be called on to evaluate inflammatory processes of the head and neck on a regular basis. We have attempted to describe the broad range of these problems, as well as our current considerations for diagnosis and management. Our goal has been to promote accurate diagnosis to allow early detection of situations calling for prompt medical or surgical intervention. PMID- 3325279 TI - Maxillofacial trauma. Evaluation and management by the emergency physician. AB - The prominent visibility of the face has placed both significant functional and aesthetic roles on it. It represents a major source of communication and sensory input for the person. Maxillofacial injuries are an infrequent cause of immediate death for the multiply traumatized patient. It is therefore extremely important for the primary physician to recognize and treat facial trauma properly, and in its proper sequence in the management of the multiply traumatized patient. PMID- 3325281 TI - [Effect of SPC 703, a new sulfonylurea derivative, on the secretion and biosynthesis of insulin by isolated pancreatic islets in the rat]. PMID- 3325280 TI - Postprandial glucose, insulin and glucagon responses to meals with different nutrient compositions in non-insulin-dependent diabetes mellitus. AB - Postprandial glycaemic and hormone responses to meals with different nutrient compositions and their heterogeneity were evaluated in 16 non-insulin-dependent diabetic patients and 5 healthy volunteers. Five kinds of nutrient stimulation- 75 g glucose, a Japanese mixed meal (400 kcal, carbohydrate 60%, protein 14%, fat 26%), a high protein meal (300 kcal, C 26%, P 64%, F 10%), a high fat meal (300 kcal, C 23%, P 5%, F 72%) and 20 g iv glucose--was given to each subject. On the average, in both normal and diabetic subjects, the increases in plasma glucose (PG) and insulin (IRI) were the largest with the oral glucose load and the smallest with the high protein meal. The ratio of increase in IRI and PG (sigma delta IRI/sigma delta PG) was the highest with the high protein meal and the lowest with the oral glucose load. sigma delta IRI with the high protein meal and the high fat meal were the same in normal and diabetic subjects. However, each of the 16 NIDDM patients and 5 normal volunteers exhibited a different pattern of response to the nutrient stimuli and no definite subgroup could be classified. There was no correlation between metabolic responses and family history of diabetes mellitus, duration of diabetes, body mass index and fasting plasma glucose. The present results suggest the nearly intact capacity of insulin secretion in NIDDM in response to a high protein or high fat meal and the difficulty of subclassification in NIDDM according to the glycaemic and hormone responses to the different nutrient stimuli. PMID- 3325282 TI - [Renin profiles in patients with diabetes mellitus]. PMID- 3325283 TI - [Neutrophils in endocrine disorders]. PMID- 3325285 TI - Enhanced susceptibility of trypsinized HeLa cells to Chlamydia trachomatis infection. AB - An improved cell culture method for the recovery of Chlamydia trachomatis from clinical samples was evaluated. Freshly trypsinized HeLa 229 cells were infected in suspension culture and compared to a standard monolayer culture method. Among 1085 specimens evaluated, 84 were positive by both methods, 978 were negative by both methods, 2 were positive by the monolayer method only, and 21 were positive by the suspension method only. Inclusion counts were two-fold higher in the suspension culture method than in the monolayer method (p less than .001). It is concluded that freshly trypsinized HeLa 229 cells infected in suspension culture are more susceptible to infection with Chlamydia trachomatis than standard monolayer cells. PMID- 3325286 TI - Enzyme immunoassay for detection of antigen in acute Plasmodium falciparum malaria. AB - A monoclonal antibody specific for an epitope of a 50 kDa Plasmodium falciparum antigen was used in an enzyme immunoassay for detection of the corresponding exo antigen in culture supernatant and in the sera of 31 patients suffering from acute malaria. The assay was specific for Plasmodium falciparum and did not appear to be strain restricted. A parasitaemia level below 0.001% could be detected. PMID- 3325284 TI - Specific and nonspecific immunodiagnostic properties of recombinant and synthetic Plasmodium falciparum antigens. AB - Six Plasmodium falciparum/beta-galactosidase fusion proteins produced by a genomic DNA expression library, and two synthetic Plasmodium falciparum antigens were applied to ELISA and tested for their immunodiagnostic properties. Results were compared to reference methods, i.e. fluorescence antibody test with whole cell antigen and ELISA with detergent-soluble crude schizont antigen. Anti Plasmodium falciparum antibodies could be detected by these molecular antigens to varying extents in human sera. Undesired reactivity to fusion proteins due to the high prevalence of antibodies to beta-galactosidase in human sera and undesired reactivity to one of the synthetic antigens (P12) frequently occurred. The antibodies responsible for the nonspecific reactivity could not be identified. It was concluded that the application of molecular Plasmodium falciparum antigens to ELISA represents a practicable approach to immunodiagnosis of malaria if the construction of epitopes that bind antibodies other than Plasmodium falciparum antibodies can be avoided. PMID- 3325287 TI - Comparison of two selective blood agar media for the culture of group A streptococci from throats. PMID- 3325288 TI - Enhanced efficacy of computerized exercise test by multivariate analysis for the diagnosis of coronary artery disease. A study of 558 men without previous myocardial infarction. AB - Multivariate analysis has been proposed to enhance diagnostic accuracy of the exercise test in coronary artery disease. To quantify the improvement given by multivariate analysis in comparison with ST segment depression alone during exercise test, 558 men without previous myocardial infarction were studied retrospectively. All the patients underwent a symptom-limited Bruce protocol with computer-averaged recordings in V5, aVF, V2. Coronary angiography was performed within the following 90 days. Prevalence of coronary artery disease (diameter narrowing of 50% or greater) was 0.56. Among 12 clinical and exercise parameters studied by stepwise multivariate analysis, five were found to reach the maximal accuracy: (1) exercise duration, (2) history of typical angina, (3) typical angina during the test, (4) age, (5) maximal heart rate. In comparison with ST depression, multivariate analysis significantly improves accuracy (74.6 vs. 66.8%, P less than 0.01) by increasing sensitivity (0.68 vs. 0.59, P less than 0.05) without affecting specificity (0.83 vs. 0.76, NS). Thus, in a group of men without infarction and a low prevalence of coronary artery disease, multivariate analysis with five easily collected variables is more accurate than ST segment depression alone during exercise. In addition, ST depression did not appear as discriminant as exercise duration for diagnostic purposes. This finding emphasises the importance of performing a symptom-limited exercise test. PMID- 3325289 TI - Captopril versus placebo in congestive heart failure: effects on oxygen delivery to exercising skeletal muscle. AB - The effects of captopril versus placebo on oxygen consumption in the exercising leg have been examined using Doppler measurements of femoral flow and arteriovenous oxygen difference. Twenty patients with heart failure were randomized to captopril 25 mg (N = 10) or placebo (N = 10). Maximal supine exercise of one leg was performed before treatment and again 1 h and 4 h afterwards. Systemic haemodynamic variables were unaffected by placebo, but captopril increased stroke index at peak exercise from 26 +/- 3 to 34 +/- 3 ml beat-1 m-2 and reduced pulmonary artery wedge pressure from 26 +/- 3 to 16 +/- 3 mmHg (P less than 0.05). Despite the captopril-induced improvement in left ventricular function, exercise duration did not increase significantly and peak values for femoral flow (1059 +/- 178 to 938 +/- 134 ml min-1, P = NS), and oxygen consumption (134 +/- 26 to 111 +/- 18 ml min-1, P = NS) in the exercising leg were unaffected. Cutaneous flow, as reflected by skin temperature (27.5 +/- 0.4 to 27.6 +/- 0.4 degrees C, P = NS), was also unaffected. In the patients randomized to captopril, the acute improvement in left ventricular function was abbreviated and, after 4 h, all variables had returned towards baseline. Moreover, when the invasive studies were repeated after four weeks chronic treatment responsiveness to converting enzyme inhibition had attenuated and there were no detectable differences between the captopril and placebo groups. These data have demonstrated an acute captopril-induced improvement in left ventricular function in patients with congestive heart failure. Nevertheless the beneficial acute response was abbreviated predicting the development of early tolerance. Oxygen delivery to the exercising leg showed no tendency to increase either acutely when left ventricular function was significantly improved, or chronically when systemic responsiveness had attenuated. Thus irrespective of its effects on left ventricular function, captopril does not increase nutritive flow to exercising skeletal muscle in congestive heart failure. PMID- 3325290 TI - A new approach to image subtraction in immunoscintigraphy: preliminary results. AB - Recently proposed image comparison software is applied to immunoscintigraphy. The software performs geometric and gray level registration of two images and generates an image of the statistically significant differences. It permits the comparison of scintigraphic images recorded at different times. It is used to subtract 113mIn and 111Inphytate colloid liver scans and early (blood pool) images from 131I or 111In-monoclonal Ab images and to compare Ab images recorded at different times. Using the procedures made possible by this software, only images recorded using the same radionuclide or using radionuclides of about the same energy are compared. Anti CEA, 19-9 and OC 125 F(ab)2 fragments labeled with 131I or 111In are used in 32 patients with 47 demonstrated recurrences or metastases of colorectal or ovarian cancers. The overall sensitivities of the unprocessed and processed images are 25/47 and 41/47 respectively. The improvement in sensitivity is particularly high in the liver when In labelled Ab are used. This technique improves the contrast of the images, but the interpretation must take into account the components of the non target activity (kidney, bone marrow, colon...) which are not removed by the image subtraction method. PMID- 3325291 TI - Longitudinal assessment of glomerular filtration rate by gamma camera and portable external detector. AB - Noninvasive isotope chelate methods to assess glomerular filtration rate (GFR) are less accurate than blood sampling. However, some measurement errors would be expected to be constant for an individual, and repeat estimations may be less variable. In 18 patients, estimates of GFR were obtained by 2 gamma camera techniques and a portable external detector at a mean interval of 1 year, to assess accuracy in predicting a change of GFR. Errors in these techniques were not significantly better than those predicted from two independent estimates. Most GFR measurement error for noninvasive methods appears to be random. PMID- 3325292 TI - TCNU: a ray of hope for designer nitrosoureas? PMID- 3325293 TI - Serum beta 2 microglobulin in multiple myeloma. A critical review. PMID- 3325294 TI - Chemotherapy in the elderly. PMID- 3325296 TI - Elevation of plasma prolactin concentrations by intravenous SCH 23390 and SKF 38393 in conscious rats. AB - The effect of the selective dopamine-1 (D-1) antagonist, SCH 23390 and the selective D-1 agonist, SKF 38393 on plasma prolactin levels was investigated in conscious, freely moving male rats. Plasma prolactin was markedly increased by the intravenous injection of either SCH 23390 or SKF 38393 in a dose-related fashion. The maximal prolactin response was observed 15 min after drug injection. The d-isomer of SKF 38393 was significantly more potent than the l-isomer. In urethane-anesthetized rats, the two drugs produced similar effects on prolactin as those in the conscious animal preparation. Both SCH 23390 and SKF 38393 potentiated the sulpiride-induced prolactin elevation. These observations suggest that pharmacologic stimulation, or blockade of D-1 receptors in the living animal, can mimic the action of a D2 antagonist at the anterior pituitary lactotroph. We have speculated on the possible mechanisms in pituitary and higher in the central nervous system which might be responsible for the prolactin changes caused by either SCH 23390 or SKF 38393. PMID- 3325295 TI - Effect of serotonin on cytosolic free calcium in adrenal glomerulosa and vascular smooth muscle cells. AB - In view of its vasoconstricting action and of its stimulating effect on aldosterone biosynthesis, serotonin (5-hydroxytryptamine, 5-HT) could play a role in the genesis and/or maintenance of hypertension. The effects are mediated by different specific receptors whose transmembrane signaling system is not elucidated. We have used the fluorescent probe quin 2 to study the effect of 5-HT on cytosolic free calcium in enzymatically dispersed bovine adrenal glomerulosa cells and in cultured rat aortic smooth muscle cells. We also examined the effect of 5-HT on prostacyclin production by rat aortic smooth muscle cells. Serotonin did not modify the level of cytosolic free calcium in adrenal glomerulosa cells. In contrast, serotonin induced rapid, concentration-dependent (10(-8) -10(-5) M) rises of cytosolic free calcium in monolayers of cultured rat aortic smooth muscle cells, from a basal level of 153 +/- 27 nM to peak levels of about 400 nM. Ketanserin (10(-6) M), a specific 5-HT2-receptor antagonist completely blocked the free calcium rise induced by 5-HT. 5-HT induced a concentration-dependent increase in 6-keto-PGF1 alpha production in smooth muscle cells, which was suppressed by ketanserin, indomethacin or removal of calcium from the incubation medium. In contrast nifedipine (10(-6) M) did not modify the response to 5-HT while it abolished the response to vasopressin and did not modify the response to angiotensin II. We conclude that the 5-HT receptors of adrenal glomerulosa cells and vascular smooth muscle cells are linked to two distinct signalling systems which mediate the different biological responses. PMID- 3325297 TI - Fasting and L-364,718 prevent cholecystokinin-induced elevations of plasma insulin levels. AB - Sulfated CCK-8 but not non-sulfated CCK-8 induced a dose-dependent increase in plasma insulin levels in fed mice. In fasted mice, however, the CCK peptides caused a non-significant to minimal elevation of plasma insulin. Refeeding fasted mice for 1 h prior to CCK-8-S administration was sufficient to cause a significant elevation of plasma insulin levels. The peripheral CCK antagonist, L 364,718, prevented the CCK-8-S-induced elevation of plasma insulin observed in fed mice. In conclusion, CCK produces a nutrition-dependent increase in plasma insulin levels in vivo via an action upon peripheral CCK receptors. PMID- 3325298 TI - [Establishing nonhuman primates as laboratory animals--past, present and future aspects]. PMID- 3325299 TI - Establishment and characteristics of five analbuminemic inbred strains of rats. AB - Five analbuminemic inbred strains of rats (AD/1, AD/2, AD/3, AD/4, AD/5) were established from Nagase analbuminemic rats (NAR). They showed no genetic differences in coat color, biochemical marker gene loci and skin grafting test. Their serum levels of total cholesterol, phospholipids, triglycerides, and beta lipoproteins were compared with normal inbred strains (L) derived from Sprague Dawley rats. Their plasma apoproteins were also examined. All inbred strains of analbuminemic rats showed hyperlipidemia progressing with age although there were slight variations in their lipid and apoprotein levels. These analbuminemic inbred strains of rats may be multigenic models of lipid metabolism abnormality. PMID- 3325300 TI - Convergence of main and accessory olfactory pathways onto single neurons in the hamster amygdala. AB - Chemoreceptor pathways from the vomeronasal organ (VNO), and main olfactory system are known to be separate as they pass into the brain, at least until the level of the amygdala. In the amygdala, vomeronasal pathways project to the posteromedial cortical nucleus (PMCN), and medial nucleus (MN). The main olfactory pathways have terminations in the posterolateral cortical nucleus (PLCN), and anterior cortical nucleus (ACN), both of which project to the PMCN and MN. The anatomy thus suggests that the PMCN and MN are sites for convergence of input from the main and accessory olfactory pathways. We have recorded single units in the amygdala and found that electrical stimulation of either the main olfactory bulbs or the VNO could drive some of the same units in the PMCN. Units were also found that were driven by one system but not the other, and units in which activity driven by one system was suppressed by stimulation of the other system. PMID- 3325301 TI - Failure of prostacyclin effect on the reversal of early ultrastructural changes in cell nuclei of adrenal cortex after complete 15-min cerebral ischemia in rabbit. AB - The experiment was carried out on 18 rabbits in two experimental groups. Group I: animals with complete 15-min cerebral ischemia infused with PGI2 for 3 min before, during and for 15-min after ischemia. Group II = control: animals with complete 15 min cerebral ischemia. In both groups, cell nuclei of the adrenal cortex were examined. In the 3rd and 6th h after ischemia numerous vesicular structures, intranuclear filaments and granulofibrillar bodies were found in the nuclei. The vesicular structures were enclosed in a single smooth membrane, some combined with the nuclear envelope, others remained independent. Amassing in karyoplasm of vesicular structures, intranuclear filaments and granulofibrillar bodies probably leads to death of the adrenal cortex cell after complete cerebral ischemia. It is suggested that vesicular structures may form as the result of disturbances in the water-electrolyte exchange between cytoplasm and karyoplasm of adrenal cells. In the experimental conditions, PGI2 did not affect the development of irreversible ultrastructural changes in adrenal cortex cell nuclei after complete prolonged cerebral ischemia. PMID- 3325302 TI - [Mutagenic and modifying effects of alcohol]. PMID- 3325303 TI - [Antioxidant properties of anti-inflammatory agents]. PMID- 3325304 TI - [Computerized ethological pharmacology]. PMID- 3325306 TI - [70 years of the fight against infectious diseases in the USSR]. PMID- 3325305 TI - Antimycotic action of methyl substituted N-(5-pyrimidinyl)benzenesulfonamide derivatives. AB - Some series of N-(5-pyrimidinyl)benzenesulfonamide variously methylated at the ring and/or sulfonamidic nitrogens and substituted at the benzene with NO2 or NH2 were synthesized and studied spectrometrically (N.M.R). When tested on several strains of Candida albicans and Candida tropicalis, some of the compounds exhibited very slight antimycotic activity. PMID- 3325307 TI - [Martyn Isaevich Gorvits (on the 150th anniversary of his birth)]. PMID- 3325308 TI - [Contribution of L. V. Gromashevskii to the development of the theory and practice of epidemiology (on the centenary of his birth)]. PMID- 3325309 TI - [The development of the physiology of blood circulation in the USSR 1917-1987]. PMID- 3325310 TI - [The development of the physiology of digestion in the USSR 1917-1987]. PMID- 3325311 TI - [The development of the physiology of the kidney and of water-salt metabolism in the USSR 1917-1987]. PMID- 3325312 TI - [The development of the physiology of respiration in the USSR 1917-1987]. PMID- 3325313 TI - [The development of research in the field of endocrinology 1917-1987]. PMID- 3325314 TI - [Studies on the dynamics of insulin secretion and the regulatory mechanism of insulin receptor in fetal rats]. AB - In order to clarify the onset of insulin secretion and the regulatory mechanism of its receptor induction in fetus, blood glucose, serum insulin and its hepatic receptor in situ in fetal rats (D18-D21) were measured and the changes of the levels of insulin and its receptor after the direct injection of glucose (1g/kg) to fetal rats in utero were investigated. In fetal rats (D18-D21), both serum insulin and glucose levels increased as pregnancy progresses and specific binding of insulin in fetal liver microsomal membranes increased on D21 of gestation, mainly due to the increase in binding affinity rather than binding capacity. After the direct injection of glucose to the fetus in utero, the rapid increase in serum insulin and the rapid decrease in insulin specific binding to liver microsomal membranes were observed in a part of D20 and all of D21 fetal rats, which was mainly due to the decrease of binding capacity. This suggests that the acute elevation of endogenous insulin level followed by the decrease of insulin specific binding in fetal rat liver is based on the down regulation mechanism of insulin receptor, because the amounts of insulin separated from liver microsomal membranes were less than one twentieth of the insulin concentration which are enough to decrease the binding capacity of hepatic receptor theoretically. In addition, the dissociation of 125I-insulin from liver microsomal membranes of glucose-treated rats were indistinguishable from that of control. From these results, it can be concluded that the onset of glucose-stimulated insulin secretion appears in fetal rats on D20 of gestation and the elevation of endogeneous insulin rapidly down-regulates the number of hepatic insulin receptor in fetal rats. PMID- 3325315 TI - [Photosensitization]. PMID- 3325316 TI - The efficacy and safety of fentiazac and diclofenac sodium in peri-arthritis of the shoulder: a multi-centre, double-blind comparison. AB - In a double-blind parallel group comparison of efficacy and safety, 19 patients with peri-arthritis of the shoulder received 200 mg fentiazac twice daily and 19 received 50 mg diclofenac sodium twice daily, with both drugs given orally for 3 weeks. In both groups, observers' verbal rating scales of pain severity at rest and on movement showed decreases that were significant by week 1. Both groups also had significant improvement in abduction, external rotation, retroversion and anteversion. At week 1, the patients reported improvement, on a verbal rating scale, of global effectiveness, but there were no subsequent changes. There were no statistically significant differences between the treatments in any of these variables. Five (26%) fentiazac-treated patients and four (21%) diclofenac sodium treated patients reported adverse effects, mostly gastro-intestinal. One case of rash in each group and one case of pruritus in a diclofenac sodium-treated patient were severe enough for the patients to be withdrawn from therapy. There were no clinically significant changes in laboratory values. It was concluded that fentiazac (400 mg/day) and diclofenac sodium (100 mg/day) were equally effective within 1 week in decreasing pain severity and improving shoulder mobility. PMID- 3325317 TI - Influenza immunization in children with cystic fibrosis. AB - Nineteen children with cystic fibrosis and aged between 5 and 13 years were randomized to receive two doses at monthly intervals of either a split-virion influenza vaccine (MFV-Ject, Institut Merieux) or a sub-unit vaccine (Fluvirin, Evans). In those completing the study, there was a satisfactory serological response. There was no statistically significant difference between the immunogenicity of the two vaccines as evaluated by haemagglutination inhibition or single radial haemolysis tests. The incidence of local side-effects was similar in the two groups. PMID- 3325318 TI - Treatment of chronic obstructive pulmonary disease with two sustained-release theophylline preparations. AB - A sustained-release theophylline preparation in capsule form was compared with standard slow-release theophylline tablets for variation in plasma theophylline concentration, effectiveness and tolerability in 30 adults with chronic broncho obstructive pathology. They were administered every 12 h and blood samples were collected after 8 days of treatment during the steady-state period. In this double-dummy crossover study, the sequence of the two regimens (sustained-release capsules versus tablets) was selected at random. The results of this study demonstrate that plasma theophylline levels remain within the therapeutic range for both preparations. Effectiveness and tolerability of the two drugs were satisfactory. PMID- 3325320 TI - Treatment of iron deficiency conditions in blood donors: controlled study of iron sulphate versus iron protein succinylate. AB - Iron protein succinylate is a new iron preparation for oral administration. In a controlled study versus iron sulphate in 40 blood donors with low levels of stored iron, treatment for 30 days with iron protein succinylate resulted in greater iron absorption compared to the reference drug. Serum iron concentration significantly increased compared with baseline values only in patients given iron protein succinylate. The amount of stored iron, evaluated by serum ferritin levels, significantly increased in both treatment groups. PMID- 3325319 TI - Response of some haemocoagulatory and haemorheological variables to maximal exercise in sedentary and active subjects. AB - The purpose of this study was to evaluate how physical conditioning is associated with haemostatic and rheological responses to strenuous exercise. A total of 25 males, divided into two groups differing in exercise fitness (14 sedentary and 11 active), underwent exercise testing on a bicycle ergometer with an initial 25 W workload increasing by the same amount every 3 min. The following variables were evaluated before and after the test: platelet count and aggregability, plasma fibrinogen, fibrinolytic degradation products, viscometry and micro-haematocrit. Significant differences in baseline values between the two groups were found only for blood viscosity. Irrespective of the group, significantly increased values were demonstrated for all the variables, except platelet aggregability and fibrinogen levels, in response to strenuous exercise. It is concluded that the possible protective effect of exercise against cardiovascular disease does not seem to be related to changes in the haemorheological and haemostatic measures evaluated. PMID- 3325322 TI - Asthma management--a new dimension. AB - This report describes a consensus on current asthma management in the UK, indicates areas of clinical concern and provides a rationale for improved therapy. PMID- 3325321 TI - Clinical experience with 0.05% halometasone/1% triclosan cream in the treatment of acute infected and infection-prone eczema in Egypt. AB - This is a report of a non-comparative trial to assess the usefulness of a 0.05% halometasone and 1% triclosan combination in a cream base in the treatment of acute infected and infection-prone eczematous skin disorders. The trial was carried out in three centres. Of the 126 patients admitted to the trial, 25 were lost to follow-up. The remaining 101 patients utilized the cream as the only treatment during the 3-week duration of therapy. Medication was applied to the lesions twice daily without occlusive dressing. The cream gave either excellent or good results in 89% of cases. Infection, which was initially present in 38 cases, disappeared within 5 days from 27 (71%) of them and within 6-10 days from a further six (16%) cases. The therapeutic effect was first noted (in 43 cases) within a mean of 2.7 days (+/- 1.01). The cream did not give rise to any serious local unwanted effects. Systemic unwanted effects were suspected in an 8-month old infant with extensive atopic dermatitis. The findings in this study substantiate those of other investigators that this halometasone/triclosan preparation combines potent and rapid therapeutic effect with excellent local and systemic tolerability. PMID- 3325323 TI - Comparison of human and porcine insulin therapies in children with newly diagnosed diabetes mellitus. AB - A multicenter, longitudinal study of children below the age of 16 years with newly diagnosed Type 1 (insulin-dependent) diabetes treated either with porcine monocomponent insulin (n = 26) or semisynthetic human monocomponent insulin (n = 26) was performed during the first 24 months after onset of diabetes. The two groups were carefully matched for age, duration of disease symptoms, initial metabolic values, islet cell antibodies and HLA-DR antigens. During the 24-month observation period there was no significant difference between the two groups in respect to the clinical course, insulin dosage, HbA1 and residual B-cell activity. No child in either group had a real remission without necessitating insulin therapy. The prevalence of insulin antibodies increased slowly and was 62% in the group treated by human insulin and 52% in the porcine insulin-treated group after 24 months. The titres were generally low and there was no statistical difference between the two groups in respect to insulin antibody formation. PMID- 3325324 TI - Counterregulation in type 2 (non-insulin-dependent) diabetes mellitus. Normal endocrine and glycaemic responses, up to ten years after diagnosis. AB - We have examined hormonal and metabolic responses to insulin-induced hypoglycaemia in 10 Type 2 (non-insulin-dependent) diabetic patients treated with tablets and 10 age, sex and weight matched control subjects. Diabetic patients were under 110% ideal body weight, had no autonomic neuropathy and were well controlled (HbA1, 7.1 +/- 0.2%). After the diabetic patients were kept euglycaemic by an overnight insulin infusion, hypoglycaemia was induced in both groups by intravenous insulin at 30 mU.m-2.min-1 for 60 min and counterregulatory responses measured for 150 min. There were no significant differences between diabetic patients and control subjects in the rate of fall (3.3 +/- 0.3 vs 4.0 +/ 0.3 mmol.l-1.h-1), nadir (2.4 +/- 0.2 vs 2.3 +/- 0.1 mmol/l) and rate of recovery (0.027 +/- 0.002 vs 0.030 +/- 0.003 mmol.l-1.min-1) of blood glucose. Increments of glucagon (60.5 +/- 5.7 vs 70 +/- 9.2 ng/l) and adrenaline (1.22 +/- 0.31 vs 1.45 +/- 0.31 nmol/l) were similar in both groups. When tested using this model, patients with Type 2 diabetes, without microvascular complications and taking oral hypoglycaemic agents show no impairment of the endocrine response and blood glucose recovery following hypoglycaemia. PMID- 3325325 TI - Genetic susceptibility to diabetes in inbred strains of mice: measurements of proinsulin mRNA and response to dexamethasone. AB - The insulin resistance produced by the recessive db mutation has led to more severe diabetes in C57BL/KsJ mice relative to that in C57BL/6J mice, suggesting genetic differences between the two strains affecting insulin production or insulin action. To assess these parameters blood glucose, serum insulin, pancreatic insulin, and proinsulin mRNA were measured in both normal and diabetic (db/db) KsJ and 6J strains. The mice were compared at 5 weeks of age, prior to the development of insulin lack known to occur with age in KsJ db/db mice. As a further provocation to insulin production, another group of the normal and db/db mice were given dexamethasone for 4 days. In normal mice there were no strain differences in blood glucose, serum insulin, pancreatic insulin, or proinsulin mRNA. Dexamethasone, presumably by augmenting insulin resistance, induced increases in serum insulin and proinsulin mRNA to the same extent in KsJ and 6J mice. In db/db mice, while blood glucose, serum insulin, and proinsulin mRNA were considerably higher than in normal mice, there were no strain differences observed. After dexamethasone the db/db mice exhibited strain differences which included higher blood glucose and higher serum insulin levels in KsJ mice. These findings were compatible with greater insulin resistance in KsJ than in 6J db/db mice. While dexamethasone treatment increased serum insulin in KsJ db/db mice, there was no augmentation of proinsulin mRNA in either strain, suggesting a limit to the insulin synthesis. Analysis of serum insulin/glucose and proinsulin mRNA/glucose ratios demonstrated a dexamethasone-induced increase in serum insulin/glucose in normal and diabetic mice of both strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325326 TI - Effects of streptozotocin-induced diabetes and diet on nitrogen loss from organs and on the capacity of urea synthesis in rats. AB - Rats with experimental streptozotocin-induced diabetes (75 mg/kg) were divided into two groups. One group was free fed (n = 8), the other group (n = 7) pair fed to a group of control animals (n = 8). The nitrogen and energy balances of the control rats were positive. In the free-fed diabetic rats the nitrogen balance was neutral and the energy balance higher than in controls. In the pair-fed diabetic rats the nitrogen balance was negative and the energy balance reduced. After 4 weeks the capacity of urea-nitrogen synthesis was: 8.1 +/- 0.6 mumol/(min 100 g body weight) (mean +/- SEM) in controls and 22.2 +/- 2.2 mumol/(min 100 g body weight) in both groups of diabetic rats. Initially, the whole body nitrogen content was 453 +/- 9 mmol. Four weeks later it was 536 +/- 19 mmol in controls, 410 +/- 21 mmol in the free-fed diabetic rats, and 315 +/- 6 mmol in the pair-fed diabetic rats. The largest changes occurred in the muscles, initially containing 278 +/- 6 mmol, 4 weeks later 328 +/- 8 mmol, compared to 234 +/- 19 in the free fed diabetic rats and 166 +/- 18 mmol in the pair-fed diabetic rats. In conclusion uncontrolled diabetes is characterised by loss of nitrogen from muscles and most other organs. The losses from some organs are preventable by increased food intake. Irrespective of food intake the hepatic dynamics of amino nitrogen conversion is changed in a way that favours protein catabolism. PMID- 3325328 TI - [Physiological and non-physiological vagotomy in athletes]. PMID- 3325329 TI - [Right atrial myxoma: echocardiographic diagnosis and review of the literature. Description of a clinical case]. AB - Two-dimensional echocardiography is the method of first choice for diagnosing right atrial myxoma. A case of right atrial myxoma, documented by two-dimensional echocardiography, is here presented. Two-dimensional echocardiography allows accurate assessment of, tumor size, site of attachment, mobility and consistency. This non-invasive technique has replaced angiocardiography in the routine preoperative evaluation of these cases. The myxomatous nature of the mass was confirmed at surgery. PMID- 3325327 TI - Hepatic estrogen and androgen receptors and binding proteins in streptozotocin diabetic male Wistar rats. AB - We have previously shown that there are decreases in the sex differences seen in certain hepatic drug and steroid metabolising enzymes in rats with early (4 day) streptozotocin-induced diabetes. We postulated that hepatic sex hormone receptors or binding proteins might be involved in modulation of the sex differences noted in metabolism. In the present study, we measured the binding kinetics of the hepatic cytosolic estrogen receptor and androgen receptor, along with the high capacity-low affinity estrogen binding protein. At 4 or 10 days post streptozotocin (60 mg/kg intravenously), there was no change in the maximum binding capacity of the estrogen receptor, nor in the hormone affinity of any of the three proteins. However, the binding capacity of the androgen receptor and estrogen binding protein in the diabetic animals was decreased to less than half of control levels. This effect could not be reversed by hormone replacement with any of the following regimens: protamine zinc insulin, 10 U/kg subcutaneously once a day; Toronto insulin, 15 U/kg subcutaneously twice a day; testosterone enanthate, 1 mg/kg s.c. once a day; triiodothyronine, 30 micrograms/kg s.c. daily; ovine growth hormone: 0.02 U/h s.c., 30 micrograms s.c. 7 times daily, 30 micrograms i.v. 4 times daily; or various combinations of these hormones. Stress, such as 4 intravenous injections of saline per day, was noted to decrease the binding capacity of the estrogen binding protein. Therefore, we measured the basal serum corticosterone levels, which were not significantly different from control values in untreated or insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325330 TI - [Treatise of Pathologic Anatomy for Physicians and Medical Students by Prof. Pio Foa (1920-1924)]. PMID- 3325331 TI - [Hypotension in pregnancy, a sequela of adrenal cortex insufficiency?]. AB - Because of certain similarities in the symptoms of hypotension and adrenal cortical insufficiency, etiological connections have long been postulated. In the prospective study reported here the behavior of plasma renin activity, angiotensin II, aldosterone and cortisol values were therefore investigated in 10 normotensive and 20 hypotensive women during pregnancy. Blood samples were taken from all women at the start of the study and 10-14 days later, in each case following orthostatic loading. Following randomization between taking blood samples, the hypotensive gravidae were given either 2 X 1 placebo tablets (n = 10) or 2 X 2.5 mg dihydroergotamine (DETMS retard) (n = 10) daily on a double blind basis and continued to take the tablets until their children were born. Among the hypotensive gravidae there were no low aldosterone or cortisol values typical of Addison's disease, nor any severely increased PRA and angiotensin II values. Therefore, adrenal cortex insufficiency can be ruled out as a cause of their hypotension. While no differences were found between the hypotensives treated with DHE and the normotensive women as regards gestation period, birth weight and body length of the newborn, statistically significant abnormalities were found among the hypotensive patients: the mean gestation period was two weeks shorter, birth weight was around 400 g lower and body length approx. 2 cm shorter. The cause of these obstetrically undesirable results among untreated hypotensive patients cannot be explained by adrenal cortical insufficiency. Rather, a prime etiologic factor seems to be a disorder of venous hemodynamics. PMID- 3325332 TI - Osmotic stress, plasma renin activity, and spermatogenesis in Vipera aspis. AB - Circulating electrolytes (Na+, K+), plasma renin-like activity, testosterone, and testis morphology were investigated in early summer during the spermatogenic progressive phase in Vipera aspis subjected to sodium loading and sodium depletion. After sodium loading, plasma sodium and plasma testosterone levels were significantly elevated compared with those of controls, while plasma renin like activity was depressed, spermiogenesis was increased, the epithelium lining the epididymis was very thick, and the Leydig cells were hypertrophied. After sodium depletion, plasma sodium and plasma testosterone levels were significantly depressed and plasma renin-like activity was significantly elevated. Spermiogenesis seemed to be slightly regressed: the epithelium lining the epididymis was very thin, and the lumen was devoid of spermatozoa. The Leydig cells were hardly visible. All the data strongly suggest that osmotic stress affects gonadal activity in the snake. V. aspis. PMID- 3325333 TI - Gonadal steroid-mediated alteration of luteinizing hormone secretion by anterior pituitary cells of young turkeys. AB - The magnitude of luteinizing hormone (LH) release during a 3-hr test incubation was diminished (P less than 0.05) when anterior pituitary cells from young turkeys were cultured for 24 to 120 hr. This trend was evident with basal LH release and with LH release induced by luteinizing hormone-releasing hormone (LH RH) or hypothalamic extract. Anterior pituitary cells were cultured with various concentrations (10(-14) to 10(-6) M) of estradiol (E2), progesterone (P4), or testosterone (T) for 24 hr and then exposed to LH-RH or control medium for 3 hr, still in the presence of steroids. Basal LH release was potentiated (P less than 0.05) when cells were cultured with 10(-8) or 10(-6) M T, but not with E2 or P4. When cells were cultured with E2, LH release in the presence of 10(-8) M LH-RH was enhanced (P less than 0.05) in a dose-dependent fashion. LH-RH mediated LH release was also enhanced (P less than 0.05) when cells were cultured with 10(-8) M P4 or 10(-6) M T. Gonadal steroids can act directly on the anterior pituitary of the young domestic turkey to modulate LH release, with T enhancing basal LH release and E2 potentiating LH-RH-mediated LH release. PMID- 3325334 TI - Steroids modulate the release of luteinizing hormone from quail pituitary cells. AB - An enzymatically dispersed pituitary preparation from male Japanese quail (Coturnix coturnix) was used to study the effects of gonadal and adrenal steroids on gonadotropin release. Cells were preincubated for 18 hr with or without steroids and then challenged with chicken luteinizing hormone-releasing hormone (cLH-RH I; Gln8-LH-RH). Preincubation with testosterone (T; 10 nM) significantly suppressed (P less than 0.05) luteinizing hormone release in response to cLH-RH I (10 ng/ml). Preincubation with 5 alpha-dihydrotestosterone (5 alpha-DHT) (10 nM) caused even further suppression of LH-RH-stimulated LH release while the same concentration of 5 beta-dihydrotestosterone and estradiol-17 beta had no effect. In addition, preincubation with corticosterone (10 nM) significantly (P less than 0.01) suppressed the amount of LH released in response to cLH-RH I. Pituitary cells from immature males, when stimulated with cLH-RH I, released LH in a dose related manner. Neither T nor 5 alpha-DHT (10 nM) altered the effect of LH-RH. These data suggest that T and 5 alpha-DHT play a role in mediating LH release in the avian pituitary while 5 beta-reduced androgens have no effect. There appears to be no androgen effect in the immature quail. In addition, corticosterone seems to be a factor in controlling gonadotropin secretion in the quail. PMID- 3325335 TI - Sequence and structural features associated with translational initiator regions in yeast--a review. AB - We have compared the translational initiator regions of 131 yeast genes. 95% utilize the first AUG from the 5' end of the message as the start codon for translation. Yeast leader regions in general are rich in adenine nucleotides (nt), have an average length of 52 nt, and are void of significant secondary structure. Sequences immediately adjacent to AUG start codons are preferred, however, the bias in nucleotide distribution (5'-A-YAA-UAAUGUCU-3') does not reflect a higher eukaryotic consensus (5'-CACCAUGG-3') with the exception of an adenine nucleotide preference at the -3 position. A minority of yeast mRNAs that contain AUG codons in the leader region that do not serve as the start codon for the primary gene product differ from the majority of mRNAs by one or more of these general properties. This analysis appears to indicate that basic features associated with yeast leader regions are consistent with a general mechanism of initiation of protein synthesis in eukaryotes, as proposed by the ribosomal 'scanning' model, but perhaps only basic features associated with ribosomal recognition of an AUG start codon are intact. PMID- 3325336 TI - Invertase gene (SUC2) of Saccharomyces cerevisiae as a dominant marker for transformation of Pichia pastoris. AB - A two-step method for the selection of transformants of prototrophic industrial strains of the methylotrophic yeast Pichia pastoris has been developed. This method is based on our observation that P. pastoris cannot use sucrose as the sole carbon source (Suc-) and that introduction of the invertase gene (SUC2) of Saccharomyces cerevisiae renders P. pastoris Suc+. P. pastoris was transformed with a plasmid which contains the SUC2 gene of S. cerevisiae and an autonomously replicating sequence PARS1 from P. pastoris. The transformants were initially allowed to regenerate on medium containing dextrose and the regenerated cells were pooled and plated on sucrose medium to screen for Suc+ transformants. It was shown that the Suc+ transformants of P. pastoris with the autonomously replicating plasmid were highly unstable with respect to the plasmid maintenance, even when grown on sucrose as the sole carbon and energy source. This high instability was attributed to an efficient cross-feeding by Suc- segregants on glucose and fructose generated due to hydrolysis of sucrose by the invertase enzyme secreted by Suc+ cells. Spontaneous integration of the plasmid DNA resulting in a stable Suc+ phenotype was also observed. However, stable Suc+ transformants were obtained more readily by integration of SUC2 into P. pastoris genome following transformation with a linearized plasmid with the ends homologous to P. pastoris HIS4 locus. All such integrants were completely stable for Suc+ phenotype after 20 generations of growth in a nonselective medium. PMID- 3325337 TI - Expression of human pancreatic secretory trypsin inhibitor in Saccharomyces cerevisiae. AB - Human pancreatic secretory trypsin inhibitor (PSTI) cDNA was expressed in Saccharomyces cerevisiae using the yeast acid phosphatase PHO5 promoter. The product encoded by the PSTI-coding cDNA was correctly processed in yeast cells, and the PSTI molecules were efficiently secreted into the medium. The amino acid composition and the N-terminal amino acid sequence of the secreted PSTI molecules were identical to those of the authentic PSTI polypeptides from human pancreas, and the product exhibited trypsin-inhibitory activity. PMID- 3325338 TI - T7 RNA polymerase can direct expression of influenza virus cap-binding protein (PB2) in Escherichia coli. AB - Influenza virus cap-binding protein (PB2; Mr 85,000) is made in Escherichia coli when the cloned cDNA is transcribed by T7 RNA polymerase. Translation begins at the probable natural start codon and also from at least five internal sites in the same reading frame. The eukaryotic initiation site is not typical of protein initiation sites of E. coli, in that the closest potential Shine-Dalgarno sequence is far (15 nucleotides) from the start codon. Nevertheless, protein synthesis initiates efficiently at this site even in competition with a strong upstream prokaryotic initiation site. PB2 is somewhat unstable in the cell, but accumulates to a level where it is easily detectable in electrophoresis patterns of total cell protein. The full-length protein and various subfragments of it are insoluble in crude extracts, but have been useful for producing antibodies. PMID- 3325339 TI - Chemical synthesis and expression of the human calcitonin gene. AB - A gene coding for the peptide hormone, human calcitonin (hCT), has been constructed and expressed in bacteria using a prokaryotic vector containing the strong T5P25 promoter and a strong ribosome-binding site. The bacterial hCT is different from the natural hCT by having an additional Met residue at the N terminus and a non-amidated C terminus. Despite these differences, the bacterial hCT is biologically active in rat cells. The results are important for future structure-function relationship studies using mutants constructed by genetic engineering. PMID- 3325340 TI - [Opopira magna, a pharmaceutical preparation from the Antidotarius magnus]. PMID- 3325341 TI - On the driving out of devils by Beelzebub in therapeutics. PMID- 3325342 TI - [Fettered spirits of disease]. PMID- 3325343 TI - [The birth of histology problematics and the Paris school of clinical medicine]. PMID- 3325344 TI - [Development of physiology in Spain in the 19th century]. PMID- 3325345 TI - [Perception and causality in the writings of the sensory physiologists Hermann von Helmholtz, Johannes von Kries and Victor von Weizsacker. A contribution to the relation of empirical theory and scientific theory in medicine]. PMID- 3325346 TI - [Developmental history of hospital pharmacy with special reference to public health]. PMID- 3325348 TI - [Research on Soemmerring]. PMID- 3325349 TI - [Hospital life in the Age of Enlightenment]. PMID- 3325347 TI - [Another book on longevity. The Pantheum Hygiasticum of Claudius Deodatus 1628]. PMID- 3325350 TI - [Byzantine hospital history]. PMID- 3325351 TI - [The role of the P-450-hydroxylase system in the evaluation of the effect of environmental factors on the body]. PMID- 3325353 TI - [Great October and the problems of occupational hygiene]. PMID- 3325352 TI - [Current problems of hygiene in relation to the presence of surface-active agents in the environment]. PMID- 3325354 TI - [Main stages in the development of Soviet industrial toxicology]. PMID- 3325355 TI - [Achievements and prospects of occupational radiation hygiene]. PMID- 3325356 TI - [Occupational hygiene and industrial-sanitary control in the Ukrainian S.S.R]. PMID- 3325357 TI - [Occupational hygiene in the Lithuanian S.S.R]. PMID- 3325358 TI - [Problem of local vibration in occupational medicine]. PMID- 3325359 TI - [Problems of the prevention of harmful effects of occupational noise]. PMID- 3325360 TI - [Results and prospects of the development of studies of occupational hygiene in exposure to ultrasound]. PMID- 3325361 TI - [Hygienic problems of occupational microclimates]. PMID- 3325362 TI - [Major problems of occupational hygiene in mechanical engineering]. PMID- 3325364 TI - [Main stages in the development of Soviet occupational pathology]. PMID- 3325363 TI - [Results and prospects of the development of occupational hygiene in the chemical industry]. PMID- 3325366 TI - [Soviet public health and the 70th anniversary of the Great October Socialist Revolution]. PMID- 3325365 TI - [Implantation of an artificial heart with calculation of the variants in its placement in the human chest cavity]. PMID- 3325367 TI - [Atresia of the pulmonary artery with an intact interventricular septum]. PMID- 3325368 TI - [Preventive use of ciprofloxacin in vaginal and abdominal hysterectomies: initial results]. PMID- 3325369 TI - [Preoperative antibiotic administration (one-shot- prevention): prevention of wound infections in gynecology]. PMID- 3325370 TI - [Responsibilities of gynecologic radiology in diagnosis and therapy]. PMID- 3325371 TI - [Value of modern imaging procedures in the primary diagnosis and after care of patients with genital cancers]. PMID- 3325372 TI - [Indications for radiotherapy in cervical and uterine cancer following operation]. PMID- 3325373 TI - [Intracavitary brachytherapy with long and short-term afterloading technic in gynecology]. PMID- 3325374 TI - [Radiation side effects and sequelae following radiotherapy of the female genital organs. Incidence, prevention, therapy]. PMID- 3325375 TI - [Significance of mammography for preventive screening of breast cancer]. PMID- 3325376 TI - [Clinical, histopathologic and mammographic prerequisites of radiotherapy in breast-sparing management of breast cancer]. PMID- 3325377 TI - 100 years ago: "first scientific demonstration of bacterial antagonisms". PMID- 3325378 TI - Naturally occurring perylenequinones. PMID- 3325379 TI - [Refraction of the eye following perforating keratoplasty]. PMID- 3325380 TI - [Clinical aspects, course and results of keratoplasty a chaud]. PMID- 3325381 TI - [Comparative intraoperative keratometry for reducing postoperative corneal astigmatism]. PMID- 3325382 TI - [HLA antigens and keratoplasty]. PMID- 3325383 TI - [Comparison of locally applied prostaglandin synthesis inhibitors in Nd:YAG laser surgery--initial results]. PMID- 3325384 TI - [Corneal endothelium and in vivo cytology of intraocular lenses]. PMID- 3325386 TI - [Relation of Polish ophthalmologists of the 19th century to German ophthalmology]. PMID- 3325387 TI - [Therapeutic experiences of hypertensive physicians]. PMID- 3325385 TI - [Congenital meningoencephalocele and its differential diagnosis]. PMID- 3325388 TI - [Ranitidine and cimetidine: effect on ulcer pain. Superior effect of ranitidine on pain symptoms in duodenal ulcer]. PMID- 3325389 TI - [The crisis in psychiatric diagnosis]. AB - The validity of psychiatric diagnosis has been in doubt recently, partly because of its unreliability and partly also as a result of sociopolitical and antipsychiatric trends. Psychiatrists rallied to meet this challenge by developing modern systems of classification. However, these were evolved with a purely descriptive intent and thus became part and parcel of "biological psychiatry". At first, the new classification systems offered the great advantage of making scientific communication easier, but they have been the target of renewed criticism because of problems such as different competing classifications, restriction of characteristic parameters to purely empirical observations, and neglect of clinically important criteria. Although diagnoses are now much more easily classified and rechecked, the development of diagnostic tools seems to have reached a limit requiring a revalidation and reconsideration of the psychopathological fundamentals of psychiatric diagnostics. PMID- 3325391 TI - Antihypertensive drugs and baroreceptor reflex control of heart rate and blood pressure. AB - The arterial baroreceptor reflex (BR; aortic and carotid sinus BR) and the cardiopulmonary BR are the most important reflexes acting as buffer systems for the maintenance of arterial pressure around a fixed physiologic value. They act as permanent inhibitory systems on the central cardiovascular structures and they can be either activated or deactivated by using selective techniques. During chronic hypertension there are structural alterations of the peripheral and/or central components of the BR that become "reset", with a shift in the function curve relating BR activity to blood pressure (BP) in the direction of higher pressure values. As a consequence of the hypertension-induced resetting phenomenon, both the threshold pressure and sensitivity of BR are disturbed. However, if BR resetting during hypertension clearly decreases the sensitivity of BR control of heart rate (HR), BR control of peripheral resistance and arterial pressure as a whole is preserved and even increased when hypertension develops. Thus, this apparent discrepancy between BR control of HR and BP during hypertension demonstrates that evaluation of an antihypertensive therapy on reflex control of HR alone cannot predict what will happen to BR control of the whole cardiovascular system. Regarding BR control of HR, in contrast to the classical arteriolar vasodilators such as hydralazine and its derivatives, the majority of the modern antihypertensive drugs do not evoke reflex tachycardia in response to lowering of BP in normotensive or hypertensive subjects. Although the intrinsic pharmacologic mechanisms of action of these drugs on BR may be quite different (e.g., alpha 1-or beta-adrenoreceptor blocking agents, converting enzyme inhibitors, certain calcium-channel blockers of the phenyldihydropyridine group, and so on), they all shift in a parallel manner the set-point of the BR response curve towards lower pressures, with no change in HR or R-R interval. Generally, this resetting phenomenon occurs after several weeks or months of antihypertensive therapy, but it can also occur acutely (e.g. after IV injection) after administration of drugs such as prazosin or ketanserin. Finally, antihypertensive agents such as clonidine and methyldopa can simultaneously reset the BR and increase its sensitivity, thus leading to almost complete restoration of control of HR response despite the concomitant decrease in BP. Regarding BR control of blood pressure, only captopril and especially celiprolol (a beta 1 adrenoreceptor blocking drug with vasodilating properties) are able to restore almost normal BR control of arterial pressure. PMID- 3325390 TI - [Self-induced water intoxication in schizophrenic patients]. AB - This case report concerns two schizophrenic patients with "psychogenic" polydipsia, without any underlying somatic disease. Although case A showed a correlation between excessive water intake and severity of psychomotor disturbance, this could not be safely diagnosed as a water intoxication because the sodium serum level was normal. The lowered sodium serum level in case B, however, allowed us to conclude that the manifestation of grand mal was a sign of a genuine water intoxication. 27 casuistic studies on 67 patients with the syndrome of self-induced water intoxication in schizophrenics are then reviewed. Finally, a variety of diagnostic and pathogenetic problems of this syndrome is discussed, with special reference to the role of inadequate ADH secretion. PMID- 3325393 TI - Captopril in the treatment of congestive heart failure. AB - This 3-part discussion of captopril, the first oral angiotensin converting enzyme (ACE) inhibitor, focuses on the clinical use and superiority of this agent to standard treatments and the new observations that use can improve the overall poor survival associated with heart failure. Today, as in the past, treatment of CHF includes digoxin and diuretics. Vasodilators have been relegated by some to the role of supplementing therapeutic regimens when patients remain symptomatic. Recently, controlled studies have shown that the introduction and supplementation of therapeutic regimens with ACE inhibitions and specifically captopril is associated with substantial clinical benefits: Symptoms are reduced as hemodynamics and exercise capacity improve, metabolic derangements (including fluid retention, potassium and magnesium loss and sympathetic nervous activation) are reduced with resultant favourable effects on arrhythmia frequency and finally the newest and most dramatic observation of improved survival. This review will briefly summarize these developments and assist in the clinically important aspects of this therapy for practicing physicians. Guidelines for the clinical use of captopril: In patients with confirmed dilated cardiomyopathy, captopril improves stroke volume in response to afterload reduction, but in volume contracted patients vasodilation may be associated with hypotension. Therefore, prior to initiating captopril, the diuretic dosage should be reduced, particularly in low serum sodium concentration states if intravascular volume is depleted. Potassium supplements should be stopped due to the expected decrease of aldosterone production and improved potassium retention. Initial therapy should be started with a low captopril dosage (2 to 3 times 6.25 mg/day), maintenance dosages are 25 or 50 mg b.i.d. or t.i.d. Superiority to other vasodilator drugs and use in mild cases: In studies of acute and chronic CHF, captopril improves hemodynamics, exercise tolerance, and reduces symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325392 TI - [Captopril in hypertensive patients with type II diabetes mellitus]. AB - Since the angiotensin converting enzyme (ACE) is identical with kininase II, the reduction of its activity by an ACE-inhibitor such as captopril will not only decrease the concentration of angiotensin II but also elevate the levels of kinins. Although the slight increase of the latter will not contribute to the antihypertensive action of ACE-inhibitors, we are sure today that it exhibits local metabolic effects in cardiac and skeletal muscle tissue. These endogenous kinins have been shown to improve the utilisation of glucose in the human forearm, the whole organism and the isolated perfused rat heart and seem to exhibit their effects via prostaglandins. A cross-over plot of the glycolytic intermediates at the height of phosphofructokinase induced by bradykinin in rat heart and the activation of the purified enzyme from rabbit heart by PGE2 point to an enhanced glycolytic rate as their mode of action. From these findings similar effects under ACE-inhibitors can be assumed. This was investigated in ten non-insulin-dependent diabetics, whose glucose disposal rate was measured by the glucose clamp technique. After 25 mg of captopril their peripheral insulin resistance was significantly improved, which was found to be due to an accelerated rate of glucose uptake into their forearm muscle tissue. To evaluate the clinical relevance of these data, 15 mildly hypertensive, overweight type II diabetic patients (mean age: 53 years; seven women) were hospitalized. After a seven-day wash-out period, the patients were given 25 mg of captopril twice daily for seven days. During the treatment, systemic kinin concentrations significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325394 TI - [ACE inhibitors and their clinical significance]. AB - With the availability of orally active angiotensin converting enzyme (ACE) inhibitors, it has become possible to chronically inhibit the renin-angiotensin system. When given to hypertensive patients as monotherapy, these agents can normalize the blood pressure in about 50% of all cases like other antihypertensive drugs. If the monotherapy is not sufficient to normalize blood pressure, the addition of a sodium depletion, for instance by administering concomitantly a diuretic, can become necessary to normalize blood pressure. The antihypertensive effect of ACE inhibitors is characterized by some particularly favorable features: ACE inhibitors attenuate the fall in serum potassium and the rise in plasma uric acid induced by diuretics, they do not cause any salt retention nor orthostatic hypotension, they do not raise pulse rate when they reduce blood pressure, and they certainly do not reduce the perfusion rate of the brain, the heart or the kidneys. The same features are apparent when using these agents in patients with congestive heart failure, in whom these drugs enhance cardiac output and exercise capacity by decreasing simultaneously pre- and afterload to the heart. Untoward effects of ACE inhibitors are relatively infrequent and they can mostly be foreseen based on an understanding of the pharmacological mechanisms of these compounds. Thus, with appropriate use, untoward effects are often completely avoided. Recent clinical studies have suggested that ACE inhibitors, when compared to other antihypertensive drugs, can improve the quality of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325395 TI - [Effect of captopril on the life expectancy of patients with chronic heart failure]. AB - Since the introduction of vasodilator therapy, progress has been realized in the management of advanced congestive heart failure (CHF) of different etiologies. The most encouraging influences on hemodynamics, exercise tolerance and symptomatology have been reported with ACE-inhibitors. While hemodynamic parameters do correlate with prognosis in CHF [11, 14, 27], the overall prognosis in CHF is very poor [19], and there is no tight correlation between symptomatology, hemodynamics and prognosis [13]. A powerful influence of ACE inhibitors has been demonstrated not only on hemodynamics and on the neuro endocrine activation in CHF [10], but also on left ventricular hypertrophy [22] and myocardial morphology [16, 23]. On the background of these therapeutic options, we designed a double-blind, randomized, placebo controlled trial on the efficacy of captopril on mortality and morbidity in chronic CHF. The basic population studied consists of patients of a large community, university affiliated hospital, with five sub-specialized divisions in internal medicine, and about 600 medical beds. All patients considered for participation live in the greater Munich area. INCLUSION CRITERIA: With slight modifications, the criteria used in the Framingham Study were used as entrance criteria [19]. Patients were randomized if they were on stable therapy for their chronic congestive heart failure usually on digitalis and diuretics. Endpoints for the double-blind treatment period were either death or severe (with digitalis and diuretics) untractable heart failure NYHA Class IV. Follow-up examinations comprised office visits of the patients every three months for a precise cardiac history over the last three months based on a questionnaire. Captopril was used in a dose of 25 mg b.i.d.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325396 TI - Oestradiol and insulin secretion in the rat: when does oestradiol start stimulating the insulin release? AB - Long-term oestradiol treatments induce hyperinsulinism and low glycaemia. Time related experiments were performed to determine when this effect appears in islets from treated rats. Oestradiol first inhibited the insulin secretion for 2 days and later stimulated the B cells functioning from the 3rd day of treatment onward. This effect of oestradiol was dose-dependent. The beginning of this stimulating action of oestradiol was characterized by a normal tolerance to glucose and normoglycaemia, still maintained in spite of hyperinsulinaemia, hypoglucagonaemia and lowered food intake. This suggested that the long-term oestradiol-induced low glycaemia was a consequence of the hyperinsulinism. PMID- 3325397 TI - Vigilance: basic and applied research. Special issue honoring Dr. Michael Loeb. PMID- 3325398 TI - Automatic and control processing approach to interpreting vigilance performance: a review and reevaluation. PMID- 3325399 TI - Vigilance research--are we ready for countermeasures? PMID- 3325400 TI - Application of vigilance research: rare, medium, or well done? PMID- 3325401 TI - Isolation and characterization of autologous blood mononuclear cells used for auto-infusion together with monoclonal antibodies in tumor treatment. AB - CO17-1A is a tumor associated antigen on colorectal carcinoma cells. A mouse monoclonal antibody of subclass IgG2A (MAb 17-1A) has been previously produced against the antigen for therapy. In a phase II study in patients with metastasizing colorectal carcinomas, leukapheresis was performed and isolated cells armed in vitro with MAb 17-1A. The mixture of MAb 17-1A and cells were infused into the patients. The aim of this procedure was to increase the number of cytotoxic cells in the tumor lesion. Two cell purification techniques (A and B) using an IBM 2991 Blood Cell Processor are described. Procedure B gave the highest yield of mononuclear cells (7.52 x 10(9) vs 5.17 x 10(9), p less than 0.01) as well as significantly higher total numbers of monocytes and NK cells. The relative ADCC activity of the two cell isolates were similar. A positive correlation between the frequency of Leu-M5+ cells (monocytes) and 51Cr release was observed. Increasing amounts of OKM1+ (CD11) cells suppressed ADCC. 35-40% of the cells bound MAb 17-1A after 1h incubation at room temperature. There was no substantial increase in cells binding MAb 17-1A upon further incubation. A strong positive correlation between the numbers of monocytes and cells binding MAb 17-1A was seen but also B lymphocytes, T lymphocytes and NK cells bound MAb 17-1A. More than 97% of the added MAb was unbound. PMID- 3325403 TI - Carcinoembryonic antigen (CEA): production of immunoprecipitating monoclonal antibodies and development of an enzyme immunoassay. PMID- 3325402 TI - Screening for anti-idiotypic monoclonal antibodies on paraformaldehyde-fixed lymphoma cells. AB - Paraformaldehyde-fixed, human lymphoma cells on glass slides were used to screen murine hybridoma supernatants for anti-idiotypic monoclonal antibodies by a rapid indirect immunofluorescence technique. The method is shown to require far fewer cells for screening than current techniques, and it provides results that correlate with the results of screening by flow cytometry or by capture ELISA. We conclude that paraformaldehyde fixation preserves the idiotypic determinants of lymphomas. The assay described in this report, therefore, has significant advantages over current methods for producing anti-idiotypic monoclonal antibodies. PMID- 3325404 TI - Interaction of the apoprotein of 40 kDa photoreactivating enzyme from Escherichia coli with deoxyribonucleic acid. PMID- 3325405 TI - Lytic enzyme induced by lysozyme mutant colitis phage and from a cloned gene. PMID- 3325406 TI - Chromotropic character of bacterial acidic polysaccharides: Part I--Induction of metachromasia in dye neutral red. PMID- 3325407 TI - [Development of viral vaccines]. AB - Great success in the control of infectious diseases has been achieved by vaccination, and especially for virus infections immunization will remain of great significance. Knowledge of the epidemiology of a virus infection, an optimum vaccination strategy as well as the feasibility of a vaccination programme are important factors. Our considerations will lead to the conclusion that further development of conventional (dead/live) vaccines has to be advanced together with "modern" vaccines (obtained by recombinant gen technology). With regard to an "AIDS-vaccine", molecular biology seems to be the method of choice. PMID- 3325408 TI - Complement activation by eggs and microfilariae of filarial parasites. AB - The complement of fresh normal rat serum was activated by filarial eggs and microfilariae (mf). C3 was deposited on the surface of Litomosoides carinii, Brugia pahangi, Brugia malayi and Dipetalonema viteae as seen by immunofluorescence. Intra-uterine and in vitro-derived mf did not bind C3. In contrast, C3 bound to the blood-derived mf of B. pahangi and B. malayi as well as exsheathed mf of L. carinii and B. malayi. Significant consumption of complement was observed with eggs of all filarial species, as well as sheathed mf of B. pahangi, B. malayi and exsheathed mf of L. carinii and B. malayi. These experiments indicated that complement was activated by filarial parasites via the alternative pathway. The bound complement promoted neutrophil-mediated adherence and cytotoxicity. PMID- 3325409 TI - Automated leucocyte adherence inhibition testing in patients with colorectal cancer. AB - This paper details our initial experiences with a semi-automated leucocyte adherence inhibition (SALAI) assay in patients with colorectal disease. Two assay systems were used. Leucocytes from blood donors and patients with different colorectal diagnoses were tested for sensitization to colorectal tumour extracts, and leucocytes from healthy blood donors were assayed with serum from blood donors or patients to determine whether the serum itself contained factors which would react with the non-sensitized leucocytes in the test system. The sensitivity of the SALAI assay using patients' leucocytes was 64%, and the specificity was 68%. Discriminant analysis did not affect the sensitivity of the assay for colorectal cancer (64%), although the specificity was increased for all patients except those with malignant disease other than colorectal cancer. The sensitivity of the SALAI assay using patients' serum was 50% but the specificity was 74%. Discriminant analysis increased the sensitivity of this assay to 80% but specificity was reduced to 61%. Thus, the SALAI assay with patients' serum, although potentially more advantageous than the assay using patients' leucocytes in the clinical setting, was less specific. Furthermore, samples from patients with early colorectal cancers were less reactive making the serum assay unsuitable for screening asymptomatic patients. The SALAI assay using patients' leucocytes, however, has a higher sensitivity than most reported variations of the assay but a slightly lower specificity. It is suggested that the SALAI assay is preferable to other methods for leucocyte adherence inhibition (LAI) testing. PMID- 3325410 TI - Studies on glycoproteins in the human malaria parasite Plasmodium falciparum. Identification of a myristilated 45kDa merozoite membrane glycoprotein. AB - A murine monoclonal antibody has been used to characterise a 45,000 Da antigen that is associated with the surface membrane of merozoites of the human malaria parasite Plasmodium falciparum. The antigen is a glycoprotein and incorporates myristic acid. PMID- 3325411 TI - Mutagenicity of certain para substituted nitrosobenzenes--a structure activity relationship. PMID- 3325412 TI - Evaluation of immunity. AB - Immunodeficiency disease is rapidly increasing in frequency. The AIDS epidemic, the increasing use of transplantation with immunosuppression, the aggressive immunotherapy, the persistent deficiencies after bone marrow transplantation--all contribute to the astronomically increasing numbers of patients with host defense failure. This review has presented my viewpoint as to the approaches which can be utilized by practitioners with varying focal points to provide diagnosis and maximize the potential for a cure today or at least to provide the beginnings of understanding from which will come the cures of tomorrow. PMID- 3325413 TI - The inflammatory theory of asthma. AB - In summary, these observations suggest a model for asthma which is summarized in Table III. Initially, mast cells and possibly other bronchial cells, e.g., alveolar macrophages, are activated either in an IgE-dependent or, in intrinsic asthma, in an IgE-independent fashion. These cells release two sets of mediators which may be either preformed or newly synthesized. One set of mediators is responsible for the immediate bronchospastic response. This bronchospasm is transient, readily reversible, and not associated with either airway inflammation or bronchial hyperreactivity. The second set of mediators, however, promote chemotaxis and activation of neutrophils and eosinophils. The subsequent bronchial inflammation causes damage and desquamation of the respiratory epithelium. The increased exposure of irritant receptors results in hyperreactive airways. In addition, these inflammatory cells induce mast cell degranulation and recurrent bronchospasm. Thus, after the initial exposure to allergen, a vicious cycle of inflammation, hyperreactivity and recurrent mast cell degranulation develops, ultimately leading to the pathological picture of chronic asthma. PMID- 3325414 TI - Maximum occlusal force levels in patients with osseointegrated oral implant prostheses and patients with complete dentures. PMID- 3325415 TI - The Swedish system of osseointegrated implants: problems and complications encountered during a 4-year trial period. PMID- 3325416 TI - The longitudinal clinical efficacy of osseointegrated dental implants: a 3-year report. PMID- 3325417 TI - Enhancement of osseointegration of tricalcium phosphate coated-titanium endosseous implants with collagen gel. PMID- 3325418 TI - Prosthetic-surgical reconstruction of the severely resorbed maxilla with iliac bone grafting and tissue-integrated prostheses. PMID- 3325419 TI - Mandibular staple bone plate: intraoral modifications. PMID- 3325420 TI - Provisional fixed restorations supported by osseointegrated implants in partially edentulous patients. PMID- 3325422 TI - Patient selection for obesity surgery. AB - Patients selected for gastroplasty should be at least 45 kg above ideal weight, between the ages of 18 and 50, and operated on in a center with good results, where team assessment and long-term follow-up is emphasized. Referral by a family doctor who provides local care and support is important. Medical complications need not be present because the idea is to prevent them, but problems such as sleep apnea, adult onset diabetes mellitus, hypertension, osteoarthritis, and infertility, which may be corrected by weight loss, increase the indication for gastroplasty. Patients should have social support and be intelligent enough to understand the postoperative diet and the need for regular follow-up. Those with a history of psychiatric admission require careful preoperative assessment by psychiatrist or psychologist and close follow-up and support. Patients should have made a good supervised attempt at dieting, have had stable weight for 3 to 5 years preoperatively, and have stopped smoking at least 6 weeks prior to operation. Tests to assess personality factors, eating habits, and motivation are developing, but more precise methods of selecting patients for gastroplasty and predicting successful and uncomplicated weight loss are still needed. PMID- 3325423 TI - Psychiatric evaluation of morbidly obese patients. AB - Psychiatric consultation should be integral to the overall evaluation of morbidly obese patients prior to any treatment but particularly before surgery. In addition to clarifying the presence or absence of diagnosable psychiatric illness, which then may affect the decision to proceed to surgery, psychiatric consultation can elicit data on psychological disturbances that are neurotic or indicative of a personality disorder or trait that may affect treatment. Important developmental and life history data contribute to an understanding of the patient and the role of eating behavior in the patient's life, which in turn aids the entire treatment team in establishing a more effective and mutually cooperative approach to treatment. PMID- 3325421 TI - Endocrine abnormalities in morbid obesity. AB - Recognizing the hormonal changes that accompany morbid obesity may prevent inappropriate investigations and treatments as well as provide rational approaches to reducing the morbidity and mortality of this disorder. The secondary nature of some of these metabolic changes can be demonstrated by overfeeding nonobese subjects. The crucial role of achieving adequate weight loss is also emphasized by the reversal of most of the hormonal abnormalities following successful weight loss. PMID- 3325424 TI - Quality of life assessment in obesity: physical, psychological, and social function. AB - This article examines the value of including patients' well being in the clinical assessment of obesity. It also deals with health status measures and the current state of so-called quality-of-life research. The few and limited studies of quality of life in obesity are reviewed and preliminary results of our own work are presented. PMID- 3325425 TI - Treatment of morbid obesity by nonsurgical means: diet, drugs, behavior modification, exercise. AB - Treatment of morbid obesity requires that the patient should achieve a negative energy balance of at least 350,000 kcal. Dietary treatment under metabolic ward control in time achieves any desired weight loss, but few morbidly obese patients can maintain dietary restriction for long enough as outpatients. The objective of both surgical and nonsurgical treatments is, in effect, to encourage (or force) the patient to diet. Drug treatment and exercise are ineffective in long-term massive obesity, but behavior therapy or jaw-wiring followed by the fitting of a waist cord can achieve worthwhile weight loss maintained for 3 years of follow up. PMID- 3325426 TI - Temporary intervention: dental splinting and the intragastric bubble. AB - Morbid obesity is a significant health problem in the United States today. This has resulted in an intensive investigation into temporary interventions for weight control. Dental splinting does not result in long-term weight loss because patients rapidly regain weight following release of jaw fixation. The Garren Edwards intragastric bubble was equally ineffective in achieving weight loss and was fraught with numerous complications. PMID- 3325427 TI - Effects of gastrointestinal surgery on ingestive behavior in animals. AB - Surgical manipulations of the gastrointestinal system can have a major impact on the ingestive behavior of animals. Particularly well-documented are the feeding and drinking effects of JIB and vagotomy. These two surgical procedures are similar in that they reduce the food intake and body weight of obese animals more than that of lean animals, and of hypothalamic obese rats more than that of genetically obese rats. Intermediate effects are obtained with other obesity models. Given the multiple etiologies of human obesity, it is not surprising that gastrointestinal surgery has variable effects in obese humans. The effects of gastric surgery on the ingestive behavior of animals have received relatively little attention. This is unfortunate because gastric bypass is now one of the most widely used methods for surgical treatment of human obesity. In light of recent developments in gastric surgical techniques and new findings concerning the gastric modulation of food intake, the effects of gastric surgery on the feeding behavior of animals should be further investigated. Much remains to be learned about the physiologic and behavioral mechanisms by which gastrointestinal surgery influences ingestive behavior and body weight. Surgical manipulations of the gastrointestinal system may affect ingestive behavior by directly altering the neural and hormonal feedback signals to the brain from the stomach, intestines, and other organs (liver, pancreas), or they may indirectly alter these feedback signals by modifying the preabsorptive and/or postabsorptive flow of nutrients. Seen from a functional perspective, the gut sends to the brain different types of messages that modulate ingestive behavior. Most attention has focused on gut satiety signals, but the gut can also be the source of painful sensations that suppress ingestive behavior. The distinction between satiety and discomfort is not always clear-cut. For example, gut distention may be satiating when it is moderate, but painful when it is extreme. Nevertheless, the distinction is an important one, and the nature of the feeding-inhibitory effects obtained in animal studies must be carefully evaluated. Ideally, obesity surgery should produce minimal aversive consequences, although whether it is possible to reduce food intake and body weight without producing any discomfort remains to be established. In addition to being a source of feeding-inhibitory cues, the gastrointestinal system may also provide excitatory cues that stimulate feeding and modify food preferences. For example, intestinal infusions of carbohydrates increase subsequent food intake under certain conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325429 TI - [Therapeutic studies with branched-chain amino acids in portasystemic encephalopathy]. AB - Published controlled clinical trials with branched chain amino acids (BCAA) in patients with portosystemic encephalopathy (PSE) are described and their results discussed. A positive effect on PSE by BCAA seems probable but without altering mortality rate. Improvement of nutritional state cannot be finally evaluated. PMID- 3325428 TI - Four-year weight loss Roux-Y gastric bypass: anastomotic reinforcement not additive. AB - There were 133 morbidly obese patients who received a Roux-Y gastric bypass in which a 12-mm gastrojejunostomy was sutured with multifilament steel (72 patients) for reinforcement or with interrupted silk (61 patients). Weight loss through 4 years was not different between the two patient groups. Moreover, weight loss in patients whose gastric stomas enlarged up to 16 mm was not different from those in whom the stomas remained at 12 mm. Stoma reinforcement with noncompliant steel did not add to long-term weight loss. PMID- 3325431 TI - Activity of fosmidomycin in an in vitro model of the treatment of bacterial cystitis. AB - The response to fosmidomycin of four strains of Escherichia coli was studied in an in vitro model of the treatment of bacterial cystitis. Three susceptible strains of E. coli responded well to relatively low concentrations of fosmidomycin: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for 13 h or more; however, when the surviving bacteria were challenged with a second dose, a reduced response was observed. When a fully resistant strain was exposed to fosmidomycin, bacterial growth was also suppressed for 13 h or more, even when the peak concentration achieved was below the conventionally determined minimum inhibitory concentration. Resistant variants which emerged after exposure to fosmidomycin were also resistant to fosfomycin in the absence of the potentiating agent, glucose-6-phosphate. In the presence of glucose-6-phosphate, complete (or partial) susceptibility to fosmidomycin and fosfomycin was retained by three of the four strains. These results suggest that fosmidomycin and fosfomycin are transported into E. coli by a similar mechanism, and that deletion of the hexose phosphate transport system does not occur following exposure to fosmidomycin in the absence of glucose-6 phosphate. PMID- 3325432 TI - Co-trimoxazole from the therapeutic viewpoint. PMID- 3325433 TI - Adverse reactions to Bactrim--a retrospective view. AB - A historical survey based on the most important literature is presented as a starting point for further discussion on the significance of possible adverse reactions reported after prescription of cotrimoxazole. The often changing and contradictory assessments made of the situation in different countries and at different times are outlined, and the difficulty of making a balanced and just evaluation of long established drugs is shown, particularly if the available data are derived primarily from spontaneous reports which, besides being almost impossible to verify, are often incomplete. PMID- 3325430 TI - [Significance of branched-chain keto acids for protein metabolism]. AB - Branched chain keto acids may offer therapeutic benefits for clinical conditions associated with nitrogen accumulation or increased proteolysis. The effects of keto acids on protein metabolism are complex. Mechanisms such as (1) transamination to the respective amino acids, (2) inhibition of proteolysis, (3) stimulation of insulin secretion, and (4) augmentation in the activity of BCKA decarboxylase need to be considered. Presently, therapy with branched chain keto acids is still experimental. PMID- 3325434 TI - Microbiological perspectives of co-trimoxazole. AB - Trimethoprim-sulfamethoxazole in vitro activity was compared with ampicillin, tetracycline, sulfonamide and trimethoprim against isolates of 24 gram-negative and 11 gram-positive species. The incidence of more than 10% of strains with minimal inhibitory concentrations above 32 mg/l was restricted to Escherichia coli, Shigella spp., Klebsiella pneumoniae, Providencia rettgeri, Morganella morganii, methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Occasionally, Streptococcus pneumoniae and Haemophilus influenzae strains with MICs above 32 mg/l were identified. Co-trimoxazole in vitro activity was superior to the comparative drugs for the majority of species. Co-trimoxazole remains an active combination against major pathogens of infections of the upper and lower respiratory, urinary tract and enteric infections with a still low incidence of resistant organisms. PMID- 3325436 TI - Organized labor and old age pensions. AB - Organized labor in the United States strongly supported pre-New Deal proposals for state pensions for the elderly. The idea that American labor, unlike its European counterparts, did not contribute to the rise of the welfare state is based on evidence from national organizations and their leaders. Review of the activities of the highly political state federations, and of the campaign for old age pensions in Massachusetts, indicates that labor, rather than middle-class reformers, was responsible for the promotion of new public welfare programs. PMID- 3325435 TI - Hematological side effects of co-trimoxazole. AB - Decrease of blood cells may be induced by either components of co-trimoxazole. Side effects of the trimethoprim component are much more frequent, particularly in risk groups. They are dose dependent, usually not severe, only rarely of clinical significance and easily treated or prevented by folate supplementation. In contrast, side effects of the sulfamethoxazole component seem to be extremely rare. They are similar to the hematological side effects of other sulfonamide drugs. They are idiosyncratic, nonpredictable and mostly mediated by the immune system. They may be of life-threatening severity and no therapy is known except termination of exposure and supportive measures such as substitution of blood cells and antiinfectious therapy by non-related antibiotics. PMID- 3325437 TI - Paraphernalia for teaching, training, and research on blood alcohol concentration. AB - Blood alcohol concentration (BAC) information and paraphernalia designed to predict or measure BAC are relatively common components of alcohol education, research, and treatment programs. The first purpose of this paper is to describe the types and the strengths and weaknesses of blood alcohol concentration paraphernalia. The second purpose is to identify the potential uses and requisite skills for operating BAC paraphernalia for teaching, training, and research. Further research is needed to define the parameters of utility of BAC paraphernalia, so that alcohol professionals can make decisions regarding the selection and use of these devices based on empirical evidence. PMID- 3325438 TI - The psychoanalytic process: a schematic model. AB - Clinical analysis can be usefully conceptualized as a process, with a locus, impetus, direction, and sequential steps. The schematic model proposed of such a process places the locus within the patient's mind; derives the impetus from the assimilative tendencies of the psychic apparatus; defines the direction from neurotic mechanisms to new consolidations; and suggests a sequence of four steps. The four steps are the resistance of character, the resistance of the transference consolidation, the resistance of the revived past, and the post analytic consolidation. A variety of advantages of a careful review of such features are described. Some of the limitations of the model are offered as well. PMID- 3325439 TI - Infant observation from before birth. AB - This paper describes research on the extension of infant observation to pre-natal life with the aid of ultrasounds. First there is some mention of the technique of ultrasounds and of the advances in our knowledge of pre-natal life brought about by it. A description of the research follows: 5-6 ultrasonographic observations lasting about one hour each starting from the 14th-18th week of pregnancy are carried out at monthly intervals till the end of pregnancy. During such observations the behaviour of the foetus is observed and each time the behaviour of the mother is also taken into account. After birth mother and child are then followed at home with infant observations as described by Bick. So far this research seems to be pointing to the possibility of detecting early markers of character already in utero. Two examples are given to illustrate this thesis. PMID- 3325440 TI - Rethinking the unconscious: the unacknowledged contribution of Edward Sapir to Claude Levi-Strauss and Jacques Lacan. AB - Sapir defined the human unconscious as a mechanism (based on phonemes learned during language acquisition) which imposes linguistic forms upon out-of-awareness 'psychic content' or 'elements of experience', rather than as a repository of repressed impulses or ideas striving for expression. In contemporary terms this activity may be regarded as unconscious information processing prequisite to experiential residues becoming available to conscious attention. It also imposes (as in 'projecting') the observer's cultural forms, modified by developmental experience, upon communications from others. This view antedates Levi-Strauss' unconscious which 'transforms' elements of the past 'into language' and Lacan's unconscious structured 'like a language'. The clinical psychoanalytic study of out-of-awareness mental processes, understood as a dialectic shaped by the discrepancy in power between analyst and patient, illuminates the unstable relationship between the words or signifiers selected by the patient from the infinite lexicon of available, usually socially shared, verbal or non-verbal language (his plane of expression) and his varied preconscious collections of signifieds, including cultural as well as personal developmental knowledge (his plane of content). PMID- 3325441 TI - Self-induced pneumoparotitis in an adolescent. Report of a case and review of the literature. AB - Pneumoparotitis is a rare cause of parotid inflammatory disease in both adults and children. A 12-year-old girl is reported who presented with recurrent bilateral parotid swelling. Radiologic evaluation revealed pneumoparotitis associated with masseter muscle hypertrophy. Further investigation revealed the self-induced nature of the condition in this teenager. Self-induced pneumoparotitis has been reported almost exclusively in adolescents who often have psychosocial problems. The clinical presentation, proposed pathophysiology, diagnosis and management of this rare condition are discussed and a review of the literature is presented. PMID- 3325442 TI - The anterior cricoid split explored via the canine model, preliminary studies. AB - Since Cotton and Seid introduced a new surgical procedure, the anterior cricoid split in 1980, the treatment of the difficult-to-extubate infant or child has changed dramatically. The mechanics of how the procedure works are poorly understood. This study was undertaken to investigate the effects of the anterior cricoid split on the cricoid cartilage. The technique was modified so as to allow placement and maintenance of an endotracheal tube but still allow normal activity in the canine subjects. Australian Shepherd puppies were divided into 3 groups. Group 1 underwent the anterior cricoid split procedure with placement of an endotracheal tube stent, Group 2 underwent the anterior cricoid split procedure without the use of a stent, and Group 3 served as controls. All animals were sacrificed at 12 weeks of age. The results show that there was an actual gap in the cricoid cartilage in all animals that underwent the anterior cricoid split procedure. Stenting with an endotracheal tube significantly increased this gap. These results suggest that in the canine model the anterior cricoid split may be used to actually increase the size of the subglottic space. PMID- 3325443 TI - [Therapeutic management and genetic counseling of pregnant patients with chronic inflammatory intestinal diseases]. PMID- 3325444 TI - [Status of current knowledge of the pathogenesis and prevention of postsplenectomy infection (OPSI or "overwhelming post-splenectomy infection"]. PMID- 3325445 TI - [Therapy of disorders of hemostasis in chronic and acute liver damage]. PMID- 3325446 TI - [Treatment of tuberculosis and atypical mycobacterial infections today]. PMID- 3325448 TI - [Susceptibility to edema in a 30-year-old patient]. PMID- 3325447 TI - [What is safe in therapy with conversion inhibitors?]. PMID- 3325449 TI - Human anti-alpha-galactosyl IgG reduces the lung colonization by murine MO4 cells. AB - The lung colonization of MO4 cells, a highly malignant murine cell line, is strongly reduced in syngeneic C3H/He mice by a prior incubation with anti-alpha galactosyl antibody (alpha-Gal Ab), a natural IgG antibody present in high titers in all normal human sera and specifically recognizing Gal alpha(1----3) structures (alpha-D-galactopyranosyl; alpha-D-Galp). The protective effect is due to a binding of alpha-Gal Ab to alpha-D-Galp end groups of MO4 cells, inducing both an increase in their sequestration into the liver and the spleen and a decrease in their sequestration into the lung. The F(ab')2 fragments of this antibody also exhibit a protective effect by inhibiting the homing of MO4 cells into the lung, without modifying their accumulation into the spleen and the liver. Since both the antibody and the alpha-galactosidase pretreatments of MO4 cells block their subsequent attachment to murine laminin in vitro, we suggest that, in this model, the lung colonization may be dependent on the alpha-D-Galp end groups exposed on the surface of MO4 cells. PMID- 3325450 TI - The portrait of an editor: William Doolin. PMID- 3325451 TI - Evaluation of impact on diabetic control of increased surveillance, and of human and U-100 insulins. PMID- 3325452 TI - Spontaneous pneumothorax: aetiology, management and complications. PMID- 3325453 TI - Biographical sketches--67. Petty. PMID- 3325454 TI - Public attitudes to kidney donation. PMID- 3325455 TI - Golden Jubilee Year 1937-1987. PMID- 3325457 TI - The state of cardiac transplantation. PMID- 3325456 TI - Oliver Fitzgerald (1910-1987). PMID- 3325458 TI - Dangers of medical imaging: facts and fiction. PMID- 3325459 TI - Sir Alfred Keogh: doctor and general. PMID- 3325460 TI - Biographical sketches. Purkyne. PMID- 3325461 TI - Biographical sketches. Fechner. PMID- 3325462 TI - Biographical sketches. Forlanini. PMID- 3325463 TI - Biographical sketches. Waksman. PMID- 3325464 TI - Biographical sketches. Hirschsprung. PMID- 3325465 TI - Biographical sketches. Fallot. PMID- 3325466 TI - Ambulatory ECG wave detection for automated analysis: a review. AB - Computerized ECG wave detection techniques have been evolving for the last three decades. Computerized ECG wave detection has been utilized in applications ranging from patient monitoring to computerized ambulatory arrhythmia detection. The most crucial part of any automatic ECG analysis is QRS detection. This review discusses adaptive and nonadaptive threshold techniques utilized in QRS detection. These techniques are suitable for software or hardware implementation. In addition, frequency domain and correlation methods for QRS detection are presented. In the summary a proposed QRS detection approach suitable for VLSI implementation is presented. This method has direct application to portable arrhythmia monitoring. PMID- 3325467 TI - ELISA measurement of antibody titer to purified protein derivative and mycobacteria-derived phosphoglycolipids: tool for diagnosing active pulmonary tuberculosis. AB - There is a continuous search for a rapid, efficient and reliable serodiagnostic technique for active tuberculosis (TB). Using ELISA (enzyme-linked immunosorbent essay) we have determined antibodies reactive to purified protein derivative (PPD) and two phosphoglycolipids extracted from Mycobacterium bovis cell wall, phosphatidyl inositol dimannoside (PID) and phosphatidyl inositol pentamannoside (PIP). Twenty-one patients of Ethiopian origin with active pulmonary TB and 20 healthy control subjects vaccinated with BCG in infancy were evaluated. A significantly higher level of immunoglobins reactive with the antigens was found among the patients with active pulmonary TB. The mean +/- SD of the OD units (x 10(3)) recorded in the sera of TB patients compared with control subjects were as follows: using PPD 250 +/- 210 vs. 120 +/- 150 (P less than 0.025); with PID 1,150 +/- 470 vs. 750 +/- 150 (P less than 0.01); and with PIP 1,170 +/- 500 vs. 780 +/- 160 (P less than 0.025). Accordingly, the sensitivity and specificity levels were: with PPD 81 and 75%, with PID 82 and 80% and with PIP 73 and 70%, respectively. Much more accuracy can be obtained by calculating the results of reactivity toward the combined free antigen assays. It is suggested that ELISA using mycobacterial derived antigens might be useful in the diagnosis and screening of active pulmonary TB in large populations, due to its rapidity and simplicity. PMID- 3325468 TI - Topical application of human fibroblast interferon (IFN) in cutaneous leishmaniasis. AB - Fifteen patients with single or multiple lesions of cutaneous leishmaniasis were randomly assigned to apply either IFN-beta-containing cream or a placebo cream base. Despite 8 weeks of therapy no significant improvement of the lesions was achieved. Although topical IFN-beta was not effective in this study, several laboratory studies suggest that IFN, particularly IFN-gamma, may be of therapeutic value in cutaneous leishmaniasis. PMID- 3325469 TI - Prevalence of postenteritis cow's milk protein intolerance. AB - The object of this study was to ascertain the frequency of postinfectious cow's milk protein hypersensitivity (CMPH). Twenty-four infants less than 3 months old were included in the study. Following hospitalization for acute gastroenteritis, the infants were given a protein hydrolysate formula for a period of 6 weeks, after which an intestinal biopsy was performed. Thereafter, a milk challenge was given. The existence of CMPH was defined as a postchallenge reduction of one or more of the mucosal disaccharidases below the normal levels for our laboratory. A bacterial etiology of the gastroenteritis was found in 10. Nineteen infants had no adverse reaction to cow's milk after 6 weeks on a hypoallergenic formula. Only two could be confidently diagnosed as having developed secondary CMPH; both had been infected by Escherichia coli 0 111. One infant had primary CMPH and one extra-intestinal CMPH. The incidence of secondary CMPH with gastrointestinal manifestations in this series was considerably less than described elsewhere. PMID- 3325470 TI - [Onchocerciasis. Transmission--clinical aspects--diagnosis--treatment--immune relations]. AB - Onchocerciasis is recognized as one of the most important filarial infections of man that involve grave dermatological disorders. The World Health Organization estimates that a total of 40 million people are suffering from this disease. Onchocerciasis means grave socioeconomic problems with very negative effects on general development in most regions where it is endemic. It often forces people to leave fertile agricultural valleys in an attempt to escape the disease and the flies that carry it. Though onchocerciasis has been known to medicine for over 100 years, it is only recently that it has started to be dealt with scientifically. In the last decade more has been learned about the parasite itself and about the medical aspects of infestation with it. This paper presents the mechanism of transmission, the clinico-epidemiological extent, the methods of diagnosis currently available, the immune response and the problems of both individual therapy and disease control. PMID- 3325471 TI - [Diagnosis of vascular impotence: comparison of Doppler sonography and arteriography]. AB - The use of Doppler ultrasonography to examine penile arteries represents an important step in the multidisciplinary evaluation of erectile dysfunction. This noninvasive method for demonstrating the presence of arterial lesions was found to have a sensitivity of 92.6% and an accuracy of 90% when compared with selective arteriography. The necessity of performing selective arteriography can be markedly reduced in cases of erectile dysfunction by investigations using Doppler ultrasonography. PMID- 3325472 TI - [Pili canaliculi, a form of uncombable hair]. AB - Two further cases of the hair abnormality described in 1973 by Dupre et al. as "cheveux incoiffables" and later (1978) termed pili trianguli and canaliculi are reported. This hair abnormality--a distinct anomaly without the associated physical or mental abnormalities encountered in other cases of uncombable hair- starts in the first year of life, tending to improve or to become entirely normal with age. The morphological characteristics of such hairs are grooves along the hairshaft (demonstrable only by scanning electron microscopy), resulting in triangular, reniform, or irregular cross-sections. Of the various terms used to designate the condition, that proposed by Ferrando et al. (1980) pili canaliculi, appears to be the most appropriate. PMID- 3325474 TI - [New developments for reconstruction of the tricuspid valve]. PMID- 3325473 TI - [Hannover synthetic moulages. A singular collection of dermatologic teaching models]. AB - Dermatological moulages rapidly lost their importance during the 1950s. The disadvantages of the classical moulage materials, plaster of Paris and wax, are pointed out. In the 1960s and 1970s modern plastics were introduced to moulage technology at the Linden Dermatological Clinic in Hannover. Silicon-caoutchouc and Vestolit-PVC were the substances used. This paper describes how the Hannover collection of plastic models was assembled and presents its current status. Wax and plastic models are set against each other in the illustrations. PMID- 3325475 TI - [Stress reaction after trauma or major surgery and multiple organ failure]. PMID- 3325476 TI - Localization of enkephalin- and neurotensin-like immunoreactivities in cat adrenal medulla. AB - Enkephalin (ENK)- and neurotensin (NT)-immunoreactivities (IR) were localized in cat adrenal medulla using immunocytochemistry. ENK was localized mainly in adrenaline cells, 70%-80% of which were heavily labelled. About 5%-10% of the noradrenaline cells were ENK-immunoreactive (IR). A dense network of ENK-IR nerves was localized among adrenaline cells. NT was localized only in the noradrenaline cells, 60%-70% of which were immunoreactive. NT- and ENK-IR were localized in separate noradrenaline cells. A dense network of NT-IR nerves was restricted among noradrenaline cells. The present findings confirm that ENK- and NT-like peptides are localized in separate adrenal medullary cells and demonstrate that also the preganglionic nerves are divided in subpopulations according to their neuropeptide content. These nerves have a selective localization among adrenaline and noradrenaline cells and may have physiological significance in the control of secretion of catecholamines and neuropeptides from adrenal medulla. PMID- 3325477 TI - Distribution of enteroglucagon- and polypeptide YY-immunoreactive cells in the gastrointestinal tract of the white-belly opossum (Didelphis albiventris). AB - Several segments of the gastrointestinal tract of the white-belly opossum Didelphis albiventris were investigated immunocytochemically for the occurrence of polypeptide YY (PYY) and enteroglucagon (GLU). PYY- and GLU-immunoreactive cells were observed in the lower part of the ileum, cecum and colon. These cells were seen to emit cytoplasmic basal processes to the neighbouring cells with a number of them reaching the glandular lumen via apical cytoplasmic process. GLU immunoreactive cells were also present in the oxyntic mucosae and in the pancreatic duct. Staining of consecutive sections for the two polypeptides, respectively, revealed the coexistence of immunoreactivity for PYY and GLU in the same cell type. PMID- 3325478 TI - Earliest renin containing cell differentiation during ontogenesis in the rat. An immunocytochemical study. AB - The differentiation of renin containing cells was studied by immunocytochemistry in normal rat fetuses by the use of highly specific renin, angiotensin I and II antisera. Renin synthesizing cells were detectable as early as the 15th day of gestation outside the nephrogen territories within the walls of mesonephrotic gonadic and renal arteries. Intrarenal differentiation began at the 17th day and progressed along the intrarenal arterial tree. AII immunostaining appeared concomitantly in the renin containing cells and developed considerably during ontogenesis, suggesting intracellular biosynthesis. It can be suggested that in the fetus newly synthesized AII may contribute to the early systemic and renal blood pressure regulation. PMID- 3325479 TI - Scanning microfluorometric measurement of immunofluorescently labelled microtubules in cultured cells. Dependence of microtubule content on cell density. AB - A method for evaluation of microtubule content in cultured cells has been developed. The method is based on scanning microfluorometric measurement of immunofluorescently labelled microtubules. The method has been applied to the comparison of microtubule content in epithelial XTH-2 cells grown in culture at various cell densities. The results have shown that the microtubule content in the cells is not dependent on their proliferative state rather than it depends on cellular contacts. PMID- 3325480 TI - Immunocytochemical localization of cathepsins B and H in rat liver. AB - Light and electron microscopic localization of cathepsins B and H in rat liver was investigated by immunoenzyme and protein A-gold techniques. For light microscopy (LM), semi-thin sections of the Epon-embedded material were stained by the immunoenzyme technique after removal of epoxy resin. For electron microscopy (EM), ultra-thin sections of the Lowicryl K4M-embedded material were stained by the protein A-gold technique. By LM, reaction deposits for cathepsins B and H were present in the cytoplasmic granules of parenchymal cells and endothelial cells, and Kupffer cells. The sinus-lining cells and the parenchymal cells showed the similar staining intensity. By EM, gold particles were present exclusively in lysosomes of all the cell types cited above. The same results were obtained from quantitative analysis. In addition, Golgi complexes themselves were mostly negative but some small vesicles on the trans side of them were labeled for these proteinases. The results indicate that cathepsins B and H are present in the lysosomes of rat liver and that these enzymes seem to be transported by small vesicles from endoplasmic reticulum to lysosomes via tubuloreticular network of the trans Golgi region. PMID- 3325481 TI - Relaxation training affects success and activation on a teaching test. AB - We studied the effects of an audiocassette-relaxation training period (ART) and its timing on success at a teaching test (lecture type), on observed tension and on a number of physiological responses. The electrical activity of the upper trapezius muscle (EMG), heart rate (HR) and blood pressure (BP), of female and male instructor candidates, were examined before, during and after the teaching test as well as during its critique. The relaxation period (18 min) was presented either on the preceding night (ARTnt) or immediately before the teaching test (ARTimm). The influence of personality (types A-B and extrovert-introvert) was also studied. ART improved success at the teaching test in both sexes. In males (but not in females), ARTimm decreased EMG level during the test, but ARTnt increased EMG at the test period as compared to the control group. In females, both ARTnt and ARTimm lowered HR more than in the control group. ARTimm lowered systolic BP in both sexes. Personality types affected the ART responses; ART was more beneficial for type A than B subjects. PMID- 3325482 TI - A model of electrical excitation of the mammalian auditory-nerve neuron. AB - A model of the mammalian auditory-nerve neuron has been developed based on the classical work of Frankenhauser and Huxley [(1964) J. Physiol. 171, 302-315], modified by McNeal [(1976) IEEE Trans. Biomed. Eng. BME-23, 329-336], and Reilly et al. [(1985) IEEE Trans. Biomed. Eng. BME-32, 1001-1011], and fine tuned to represent physiological data obtained from single auditory-nerve fiber experiments in squirrel monkeys. The model is capable of reproducing neural action potential waveforms due to electrical stimulation, and can reliably predict action potential thresholds and strength-duration curves. This paper explains the derivation of the mathematical model and the effects of varying certain independent parameters including fiber diameter, length of the nodes of Ranvier, internodal length, and myelin thickness. The model parameters were selected according to the anatomical findings of Liberman and Oliver [(1984) J. Comp. Neurol. 223, 163-176], and Liberman (Pers. Commun.). The length of the unmyelinated termination of the auditory-nerve that survives after aminoglycoside damage to the inner ear has not been experimentally determined. Therefore, it was investigated as an independent variable in the model. An unmyelinated terminal length of 10.0 micron was found to most accurately describe the experimental neural strength-duration curves obtained from aminoglycoside-deafened squirrel monkeys. The parameter that had the next most significant effect on the model was fiber diameter which affects all conduction pathways, across the membrane and through the fiber. Finally the results of the model are compared with behavioral data obtained from patients and monkeys implanted with cochlear prostheses. In the companion paper [(1987) Hear. Res. 31, 267-286] predictions of the model are quantitatively compared with single-neuron data from squirrel monkeys. PMID- 3325483 TI - Production and specificity of monoclonal antibodies and polyclonal antibodies to Escherichia coli. AB - Monoclonal antibodies were produced to whole cells of heat-treated Escherichia coli. Balb/c mice were immunized with a pool of five strains of heat-treated E. coli, and the resulting hybridomas were screened by indirect immunoassay. E. coli strains other than those used for immunization were used for screening to detect hybridomas producing antibody that reacted with a large number of E. coli strains. Of 864 hybridomas, 32 reacted strongly with either two or all three of the strains used for screening; 15 were successfully cloned. Antibody from hybridoma 6H2 reacted with 35 of 68 (51%) E. coli; of 13 non-E. coli tested, only Enterobacter agglomerans was weakly positive. Hybridoma 9B12 antibody reacted with all six E. coli tested. Hybridoma 9B12, however, stopped producing antibody. Five hybridomas produced antibody which reacted with a majority of the bacteria tested whereas antibodies from two other hybridomas reacted with several E. coli and non-E. coli. Polyclonal antibodies produced to two strains of E. coli varied in the numbers of E. coli with which they reacted; both antisera cross-reacted with several non-E. coli. PMID- 3325484 TI - Effects of high-frequency jet ventilation on arterial baroreflex regulation of heart rate. AB - Fifteen anesthetized mechanically ventilated patients recovering from multiple trauma were studied to compare the effects of high-frequency jet ventilation (HFJV) and continuous positive-pressure ventilation (CPPV) on arterial baroreflex regulation of heart rate. Systolic arterial pressure and right atrial pressure were measured using indwelling catheters. Electrocardiogram (ECG) and mean airway pressure were continuously monitored. Lung volumes were measured using two linear differential transformers mounted on thoracic and abdominal belts. Baroreflex testing was performed by sequential intravenous bolus injections of phenylephrine (200 micrograms) and nitroglycerin (200 micrograms) to raise or lower systolic arterial pressure by 20-30 Torr. Baroreflex regulation of heart rate was expressed as the slope of the regression line between R-R interval of the ECG and systolic arterial pressure. In each mode of ventilation the ventilatory settings were chosen to control mean airway pressure and arterial PCO2 (PaCO2). In HFJV a tidal volume of 159 +/- 61 ml was administered at a frequency of 320 +/- 104 breaths/min, whereas in CPPV a tidal volume of 702 +/- 201 ml was administered at a frequency of 13 +/- 2 breaths/min. Control values of systolic arterial pressure, R-R interval, mean pulmonary volume above apneic functional residual capacity, end-expiratory pulmonary volume, right atrial pressure, mean airway pressure, PaCO2, pH, PaO2, and temperature before injection of phenylephrine or nitroglycerin were comparable in HFJV and CPPV. Baroreflex regulation of heart rate after nitroglycerin injection was significantly higher in HFJV (4.1 +/- 2.8 ms/Torr) than in CPPV (1.96 +/- 1.23 ms/Torr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325485 TI - Airway closure with methacholine-induced bronchoconstriction. AB - We examined airway closure with methacholine-induced bronchoconstriction in eight normal seated adults at a mean lung volume of 39% total lung capacity. Closure was evaluated in two ways. Regional closure was examined by comparing the regional distributions of 133Xe boluses distributed according to N2O uptake with those distributed by pulmonary perfusion; regions that exhibited less N2O uptake than perfusion were interpreted as having airway closure. In addition, we measured single-breath washouts of the same boluses; differences between the washouts indicated closure that was not necessarily regional. Basal airway closure increased with methacholine inhalation from 21 +/- 3 to 46 +/- 4% (means +/- SE; P less than 0.001). This was due to both decreased basal N2O uptake and a relative increase of basal perfusion. Washout curves of boluses distributed by perfusion did not change with bronchoconstriction. Before bronchoconstriction, washouts of boluses distributed by N2O uptake did not differ significantly from those distributed by perfusion. During bronchoconstriction, single-breath washouts of boluses distributed by N2O uptake showed increased concentration differences (P less than 0.015) that were significantly greater than those resulting from boluses delivered by perfusion. Changes in basal closure did not correlate with washout changes. We conclude that methacholine inhalation induced bronchoconstriction-increased basal airway closure and also increased airway closure in other lung regions in a way that did not relate to basal closure. PMID- 3325486 TI - Insulin action and secretion in endurance-trained and untrained humans. AB - To evaluate insulin sensitivity and responsiveness, a two-stage hyperinsulinemic euglycemic clamp procedure (insulin infusions of 40 and 400 mU.m-2.min-1) was performed on 11 endurance-trained and 11 untrained volunteers. A 3-h hyperglycemic clamp procedure (plasma glucose approximately 180 mg/dl) was used to study the insulin response to a fixed glycemic stimulus in 15 trained and 12 untrained subjects. During the 40-mU.m-2.min-1 insulin infusion, the glucose disposal rate was 10.2 +/- 0.5 mg.kg fat-free mass (FFM)-1.min-1 in the trained group compared with 8.0 +/- 0.6 mg.kg FFM-1.min-1 in the untrained group (P less than 0.01). In contrast, there was no significant difference in maximally stimulated glucose disposal: 17.7 +/- 0.6 in the trained vs. 16.7 +/- 0.7 mg.kg FFM-1.min-1 in the untrained group. During the hyperglycemic clamp procedure, the incremental area for plasma insulin was lower in the trained subjects for both early (0-10 min: 140 +/- 18 vs. 223 +/- 23 microU.ml-1.min; P less than 0.005) and late (10-180 min: 4,582 +/- 689 vs. 8,895 +/- 1,316 microU.ml-1.min; P less than 0.005) insulin secretory phases. These data demonstrate that 1) the improved insulin action in healthy trained subjects is due to increased sensitivity to insulin, with no change in responsiveness to insulin, and 2) trained subjects have a smaller plasma insulin response to an identical glucose stimulus than untrained individuals. PMID- 3325487 TI - Relationship between lactate threshold during running and relative gastrocnemius area. AB - This study examined the relationship between the work rate at which blood lactate accumulation begins (lactate threshold) during running and relative gastrocnemius area in four different groups. Twenty nonathletic and 11 athletic boys (age 9-12 yr), 15 female adult runners, and 11 male nonathletic students participated in this study. The muscle composition of the leg and thigh were measured by ultrasound. The lactate threshold was assessed in terms of both the absolute work rate (ml.kg-1.min-1) and relative work rate. The relative cross-sectional area of the gastrocnemius to the plantar flexor (relative gastrocnemius area) was significantly negatively related to the absolute and relative lactate threshold in all groups. These results suggest that the relative gastrocnemius area may play an important role in determining the relative and absolute lactate threshold during running. PMID- 3325488 TI - Reversal of fatigue during prolonged exercise by carbohydrate infusion or ingestion. AB - Seven cyclists exercised at 70% of maximal O2 uptake (VO2max) until fatigue (170 +/- 9 min) on three occasions, 1 wk apart. During these trials, plasma glucose declined from 5.0 +/- 0.1 to 3.1 +/- 0.1 mM (P less than 0.001) and respiratory exchange ratio (R) fell from 0.87 +/- 0.01 to 0.81 +/- 0.01 (P less than 0.001). After resting 20 min the subjects attempted to continue exercise either 1) after ingesting a placebo, 2) after ingesting glucose polymers (3 g/kg), or 3) when glucose was infused intravenously ("euglycemic clamp"). Placebo ingestion did not restore euglycemia or R. Plasma glucose increased (P less than 0.001) initially to approximately 5 mM and R rose (P less than 0.001) to approximately 0.83 with glucose infusion or carbohydrate ingestion. Plasma glucose and R then fell gradually to 3.9 +/- 0.3 mM and 0.81 +/- 0.01, respectively, after carbohydrate ingestion but were maintained at 5.1 +/- 0.1 mM and 0.83 +/- 0.01, respectively, by glucose infusion. Time to fatigue during this second exercise bout was significantly longer during the carbohydrate ingestion (26 +/- 4 min; P less than 0.05) or glucose infusion (43 +/- 5 min; P less than 0.01) trials compared with the placebo trial (10 +/- 1 min). Plasma insulin (approximately 10 microU/ml) and vastus lateralis muscle glycogen (approximately 40 mmol glucosyl U/kg) did not change during glucose infusion, with three-fourths of total carbohydrate oxidation during the second exercise bout accounted for by the euglycemic glucose infusion rate (1.13 +/- 0.08 g/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325489 TI - Dynamics of hepatic lactate and glucose balances during prolonged exercise and recovery in the dog. AB - The present experiments were undertaken to assess dynamics of hepatic lactate and glucose balance in the over-night-fasted dog during 150 min of moderate-intensity treadmill exercise and 90 min of exercise recovery. Catheters were implanted chronically in an artery and portal and hepatic veins 16 days before experimentation. 3-3H-glucose was infused to determine hepatic glucose uptake, as well as tracer-determined glucose production by isotope dilution (Ra). At rest, net hepatic lactate output was 0.33 +/- 0.15 mg.kg-1.min-1 and increased to 2.26 +/- 0.82 mg.kg-1.min-1 after 10 min of exercise, after which it fell such that the liver was a net lactate consumer by the end of exercise and through recovery. In contrast to the rapid release of lactate, net hepatic glucose output rose gradually from 2.58 +/- 0.20 mg.kg-1.min-1 at rest to 8.87 +/- 0.85 mg.kg-1.min-1 after 60 min of exercise, beyond which it did not change significantly until the cessation of exercise. Hepatic glucose uptake at rest was 1.38 +/- 0.42 mg.kg 1.min-1 and did not change appreciably during exercise or recovery. Absolute hepatic glucose output (net glucose output plus uptake) rose from 3.96 +/- 0.45 mg.kg-1.min-1 at rest to 10.20 +/- 1.09 mg.kg-1.min-1 after 60 min of exercise and was 9.65 +/- 1.15 mg.kg-1.min-1 at 150 min of exercise. Ra rose from 3.34 +/- 0.21 mg.kg-1.min-1 to 7.58 +/- 0.73 and 8.59 +/- 0.77 mg.kg-1.min-1 at 60 and 150 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325492 TI - An interview with H. Lou Gibson, RBP, FBPA. Interview by John Swartz. PMID- 3325490 TI - Running endurance in 27-h-fasted humans. AB - Nine male marathon runners were exercised to exhaustion to determine the effects of a 27-h fast on endurance performance. Each subject completed two exercise tests at the same treadmill speed (set at 70% maximal O2 uptake), one following a 27-h fast and one 3 h after a preexercise meal, in random order. Fasting caused a 44.7 +/- 5.8% (SE) decrease in endurance performance (P less than 0.01). Blood, muscle, psychological, and ventilatory data were examined to determine the cause of the decreased performance. Fasting caused significant increases in O2 uptake (9.3 +/- 2.0%), heart rate (8.4 +/- 2.4%), and rating of perceived exertion, ventilation, and psychological fatigue, evident within the first 60 min of exercise. There were no differences in plasma glucose or epinephrine levels. Muscle glycogen degraded at the same rate (0.482 +/- 0.146 vs. 0.470 +/- 0.281 mumol.g-1.min-1 in the nonfasted and fasted tests, respectively) despite lower respiratory exchange ratio and elevated free fatty acid levels, which may partially explain the elevated O2 uptake. Lactate, insulin, and norepinephrine were all increased in the fasted test (P less than 0.05). The increase in norepinephrine (r = 0.79, P less than 0.01), the diameter of type I muscle fibers (r = 0.70, P less than 0.05), and ending insulin levels (r = -0.88, P less than 0.01) were correlated with endurance time in the fasted state. Fatigue in endurance running for 27-h fasted humans appears to be related to a combination of physiological, psychological, metabolic, and hormonal changes. PMID- 3325491 TI - Rapid fluorogenic enumeration of Escherichia coli in selected, naturally contaminated high moisture foods. AB - An assay for the enzyme glucuronidase was used to determine the presence of Escherichia coli in selected, naturally contaminated high moisture foods. Raw pork sausage, ground turkey, and ground beef were inoculated into tubes containing the substrate 4-methylumbelliferyl beta-D-glucuronide (MUG) in lauryl tryptose (LT) medium. After incubation at 35 degrees C for 24 h, the inoculated LT-MUG tubes were examined under longwave ultraviolet light for the presence of a fluorogenic glucuronidase end product. A fluorescing tube indicated the presumptive presence of E. coli. The 10 day most probable number method of the AOAC and the LT-MUG procedure gave comparable recoveries of E. coli. PMID- 3325493 TI - Prevention of pre- and perinatal acquired hearing defects, Part I: Study of causes. AB - After recalling some notions of embryology, the authors review in the light of recent literature the main causes of prenatal acquired hypoacusias (of viral, bacterial, parasitic, endocrinologic, toxic or other origins) and of perinatal acquired hypoacusias (prematurity, neonatal hypoxia, obstetrical traumatism, nuclear icterus, toxicity and others) by following a systematic course (incidence, clinical signs in the mother and child, audiologic diagnosis, anatamopathology, physiopathology, prevention, and treatment). PMID- 3325494 TI - A comparative study of captopril & propranolol in essential hypertension. PMID- 3325496 TI - Malnutrition related diabetes mellitus. PMID- 3325495 TI - Acute myocarditis in association with Klebsiella pneumonia. PMID- 3325497 TI - Malpractices and renal transplantation. PMID- 3325498 TI - Regulation of reductive production of succinate under anaerobic conditions in baker's yeast. AB - When baker's yeast grown aerobically on ethanol as a carbon source was anaerobically cultured in a medium containing glucose, the activity of a cytoplasmic fumarate reductase irreversibly catalyzing the conversion of fumarate to succinate increased, reaching about 3 times the original activity after 12 h, while the activity of succinate dehydrogenase was almost lost after 10 h. These results indicate that the citrate cycle is partially modified to become a reductive pathway leading to succinate during the anaerobic cultivation. In non proliferating cells grown anaerobically on glucose, the rates of accumulating succinate and pyruvate were decreased and increased, respectively, with increasing concentrations of L-aspartate or NH4Cl in the medium containing glucose as a substrate. These changes were accompanied with increase in the cellular content of aspartate, an inhibitor of pyruvate carboxylase that is involved in supplying the intermediates of the citrate cycle, and pyruvate, a substrate of the enzyme. The aminotransferase inhibitor, aminooxyacetate, prevented the changes in succinate accumulation and cellular aspartate following the addition of NH4Cl. The addition of L-glutamate caused a marked increase in the rate of succinate accumulation without changing the cellular content of aspartate. Neither L-glutamate nor L-aspartate had the ability to produce succinate. The rate of glucose consumption was not changed upon adding these nitrogen compounds. Similar findings were also observed in experiments using proliferating cells. This report presents evidence that in cells containing a large amount of the fumarate reductase, the production of succinate from glucose is regulated by the cellular level of aspartate through the pyruvate carboxylase reaction and that glutamate regulates the succinate production by a mechanism distinct from that involved in the regulation by L-aspartate. PMID- 3325499 TI - Expression of murine interleukin-2 cDNA in E. coli and biological activities of recombinant murine interleukin-2. AB - Murine interleukin-2 (MIL-2) cDNA was inserted into an expression vector carrying an Escherichia coli tryptophan promoter and was expressed in E. coli. Recombinant MIL-2 produced by E. coli supported the growth of murine CTLL-2 cells, but not that of human T-cell blasts. Recombinant MIL-2 strongly inhibited the binding of recombinant human IL-2 (HIL-2) to murine responder cells, but only very weakly inhibited the binding to human responder cells. Moreover, recombinant MIL-2 induced secondary alloantigen specific cytotoxic T lymphocytes (2 degrees CTL) from memory CTL and activated natural killer (NK) cells in murine systems in the same manner as recombinant HIL-2. The results suggest that the species hierarchy (that MIL-2 derived from native cell culture does not act on human T-cells) is due to the protein moiety, not the sugar moiety, and is to be ascribed to the difference in binding affinity of MIL-2 and HIL-2 to murine and human responder cells respectively, and that recombinant MIL-2 shares identical biological and immunological activities with recombinant HIL-2. Thus, MIL-2 might be a convenient tool for extensive studies of the pharmacological and physiological activities of IL-2 in murine models. PMID- 3325500 TI - Role of unique consecutive glutamine repeats in active murine interleukin-2 molecule. AB - Murine interleukin-2 (MIL-2) cDNA deleted of 11 repeats of a CAG sequence, and that encoded from 33Met to 149Gln were inserted into an expression vector carrying an Escherichia coli tryptophan promoter and were expressed in E. coli, respectively. Recombinant MIL-2 deleted of 11 glutamine repeats (MIL-2(-Gln] supported the growth of murine CTLL-2 cells but recombinant MIL-2 initiated from 34Asp (34Asp-MIL-2) did not. The growth of human T-cell blasts was not supported by MIL-2(-Gln) or 34Asp-MIL-2. MIL-2(-Gln) had identical biological and immunological activities with intact MIL-2, but 34Asp-MIL-2 did not. These results suggest that the consecutive glutamine repeats do not play a role in the biological and immunological activities of MIL-2, but that the peptide sequence around them does, and the species hierarchy that MIL-2 does not act on human lymphocyte is not due to the presence of glutamine repeats in MIL-2. PMID- 3325501 TI - Conversion of Trp 62 of hen egg-white lysozyme to Tyr by site-directed mutagenesis. AB - An expression plasmid for hen egg-white lysozyme in Saccharomyces cerevisiae was constructed by inserting almost full-length cDNA (about 600 base pairs) encoding hen egg-white pre-lysozyme into a yeast expression vector, pAM 82. The hen lysozyme was expressed under the control of the repressible acid phosphatase promoter of pAM 82 in S. cerevisiae. About half of the expressed lysozyme was secreted in the yeast growth medium as a precise mature protein which exhibited specific activity consistent with that of authentic hen egg-white lysozyme. The replacement of Trp 62 of hen egg-white lysozyme with a tyrosine residue was performed by site-directed mutagenesis using a 19-mer oligodeoxyribonucleotide. The mutant lysozyme with Tyr 62 was found to exhibit enhanced bacteriolytic activity. PMID- 3325502 TI - DNA polymerase A and its stimulative factor of baker's yeast: purification and characterization. AB - DNA polymerase A (I or major) and its stimulative factor were purified from 15-20 kg wet weight of baker's yeast by several procedures, which were varied in order to examine the possible occurrence of proteolysis. The extraction was carried out in the presence of 10 or 3 mM phenylmethylsulfonyl fluoride (PMSF), followed by either batchwise adsorption-elution or column chromatography on DEAE-Sepharose (rapid or time-consuming, respectively). These early steps were followed by column chromatographies on DEAE-, CM-, and heparin-Sepharoses, phosphocellulose, and Sephacryl S-300. Preparations of the polymerase obtained by all the procedures described above showed a single protein band at Mr of about 145,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), unless they had been treated with 2-mercaptoethanol (ME). After ME treatment, however, they showed two protein bands at Mr of about 145,000 and 75,000 in SDS-PAGE, except for those obtained by the procedure involving 10 mM PMSF and the batchwise adsorption-elution. All the preparations described above showed practically the same specific activity. This indicates that in intact cells, the polymerase consisted of a single peptide with Mr of about 145,000, and that after cell disruption, it was artificially hydrolyzed in a limited fashion into two peptides with Mr of about 75,000, which were still active and were linked to each other through a disulfide bond. Preparations of the factor obtained by all the procedures described above showed a single protein band at Mr of about 20,000 in SDS-PAGE before and after ME treatment. The relative activities of the purified polymerase were (100%), 123, 21, 37, 196, and 38% with native and denatured salmon sperm DNA, native and denatured calf thymus DNA, poly(dA-dT), and poly(dA).oligo(dT)10, respectively. With the addition of the purified factor, they were 173, 272, 173, 217, 173, and 247%, respectively, i.e., significantly stimulated. The purified factor also stimulated the activity of calf thymus DNA polymerase alpha by 150% with denatured salmon sperm DNA; Km was about 5 X 10( 10)M, practically the same as that of yeast DNA polymerase A. However, it hardly influenced the activities of Escherichia coli enzyme I or Micrococcus luteus enzyme. PMID- 3325503 TI - The effect of polymerization of horseradish peroxidase on the peroxidase activity in the presence of excess H2O2: a background for a homogeneous enzyme immunoassay. AB - The phenol oxidation catalyzed by horseradish peroxidase (HRP) is slowed down by the presence of excess H2O2. This inhibition is due to accumulation of Compound III, which is a catalytically sluggish form of HRP. When HRP is polymerized through covalent bonds, Compound III becomes unstable and the peroxidase activity is less sensitive to excess H2O2. Under suitable experimental conditions, the phenol oxidation is increased by about 20-fold upon polymerization of the enzyme. This fact represents the principle of a homogeneous enzyme immunoassay reported by Hoshino et al. (J. Biochem. 97, 113-118 (1985)). The ratio of the peroxidase activities of monomeric and polymerized HRPs is 1 : 4 when phenol is replaced by resorcinol, and the difference is no larger when guaiacol and catechol are used as electron donors. PMID- 3325504 TI - Variations in the enzymatic properties of human complement subcomponent C1s by treatment with human plasma kallikrein. AB - We have investigated the effect of plasma kallikrein digestion upon hydrolytic activities of human C1s. Incubation of C1s (85 kDa) with plasma kallikrein led to progressive cleavages on the heavy chain to yield C1s-K1 (70 kDa) then C1s-K2 (53 kDa). Although these cleavages caused little change in the C2 hydrolytic and esterase activities of C1s, a marked loss in the C4 hydrolytic activity was observed. C1s-K1 and C1s-K2 were purified by DE-52 chromatography and it was found that the proteolysis of C1s into C1s-K1 was accompanied with a decrease in the C4 hydrolytic activity. Although the turnover numbers for the hydrolysis of C4 by C1s-K1 and C1s-K2 were almost the same as that of intact C1s, the Kms for C4 of C1s-K1 and C1s-K2 were found to be increased to 10 times that of intact C1s. This result suggests that the apparent decrease in the C4 hydrolytic activity upon plasma kallikrein digestion of C1s is not due to disruption in the active site but is due to decrease in the affinity between C4 and the C1s derivatives. In support of this assumption, C1s-K1 was found to be devoid of the ability to bind C4b-Sepharose. C1s is capable of forming a dimer through the C1s binding domain in the N-terminal side of the heavy chain. Although C1s-K1 is still capable of forming a dimer, C1s-K2 fails to form a dimer, suggesting that the N-terminal C1s-binding site is released during cleavage of C1s-K1 into C1s K2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325506 TI - A chicken embryo-specific myosin light chain (L23) appears to be identical with one of brain myosin light chains. AB - A novel embryo-specific myosin light chain of 23 kDa molecular weight (L23) was found previously in embryonic chicken skeletal, cardiac, and smooth muscles (Takano-Ohmuro et al. (1985) J. Cell Biol. 100, 2025-2030). When we examined myosin in embryonic and adult brain by two-dimensional electrophoresis, 23 kDa myosin light chain present in brain (Burridge & Bray (1975) J. Mol. Biol. 99, 1 14) comigrated with L23. Two monoclonal antibodies, EL-64 and MT-185d, were applied to clarify the identity of the brain 23 kDa myosin light chain and the chicken embryonic muscle L23. The two antibodies recognize different antigenic determinants in the L23 molecule; the former antibody is specific for L23, whereas the latter recognizes the sequence common to fast skeletal muscle myosin light chains 1 and 3, and also L23. The immunoblots combined with two-dimensional gel electrophoresis showed that both EL-64 and MT-185d can bind to the brain 23 kDa myosin light chain as well as the chicken embryonic muscle L23. These results indicate that chicken brain and chicken embryonic muscles contain a common myosin light chain of 23 kDa molecular weight. PMID- 3325505 TI - The potentiations by insulin-stimulating peptide from bovine serum albumin of the effects of insulin mimickers and insulin in stimulating glucose utilization by rat adipocytes. AB - An insulin-stimulating peptide derived from bovine serum albumin by digestion with trypsin was shown to inhibit insulin degradation. Addition of this peptide (1.2 microM) to the medium of isolated rat adipocytes markedly inhibited the degradation of insulin in the medium, but had a little effect on degradation of cell-associated insulin. Moreover, this peptide did not prevent dissociation of cell-associated insulin, suggesting that it is a bacitracin-type, not a chloroquine-type inhibitor of insulin degradation. The peptide also potentiated the stimulation by insulin mimickers of glucose oxidation by rat adipocytes, strongly indicating that it has some other effects besides inhibition of insulin degradation. Therefore, the effect of the peptide on activation of pyruvate dehydrogenase (PDH), one of the postbinding actions of insulin, was studied. Addition of the peptide (4 microM) to adipocytes was found to activate PDH in the absence or presence of insulin. This stimulatory effect of the peptide on PDH was dose-dependent and was observed in both whole cells and subcellular fractions of rat adipocytes. The peptide also stimulated PDH in a subcellular system of either plasma membranes and mitochondria or mitochondria only. Sodium fluoride, an inhibitor of phosphatase, blocked the action of the peptide almost completely, suggesting that the stimulatory effect of the peptide on PDH activity is at least partly due to its activation of PDH phosphatase. The mechanisms of action of the peptide are discussed. The peptide should be useful in studies on modulation of the action of insulin. PMID- 3325507 TI - Molecular assembly of the lipoprotein trimer on the peptidoglycan layer of Escherichia coli. AB - The molecular assembly of the major outer membrane lipoprotein on the peptidoglycan layer was studied using two hybrid genes coding for different OmpF lipoprotein hybrid proteins. One gene codes for a "lipoprotein" in which the diacylglyceryl cysteine residue is replaced with the Ala-Glu residue of the NH2 terminus of the OmpF protein (hybrid protein I). The other gene codes for the lipid-free "lipoprotein" from which the COOH-terminal lysine residue was further deleted (hybrid protein II). Hybrid protein I existed as a trimer. A significant portion of it was found to be composed of only the free form, which was noncovalently associated with the peptidoglycan layer. The purified hybrid protein I trimer was dissociated into the subunit in the presence of guanidine HCl and reassociated on dialysis. Both the native and reassociated trimers were bound to the lipoprotein-free peptidoglycan layer. No enhancement of the binding was observed when the reassociation reaction was carried out simultaneously. Hybrid protein II, on the other hand, did not exhibit association with peptidoglycan in both the cellular fractionation and in vitro binding experiments, although it existed as a trimer. It is concluded that 1) the protein domain of the lipoprotein exists as a trimer which is noncovalently as well as covalently associated with the peptidoglycan layer and 2) although the deletion of the COOH terminal lysine residue did not interfere with the trimerization, it interfered with the noncovalent interaction with the peptidoglycan layer. PMID- 3325508 TI - Trauma, sepsis, and the immune response. AB - Burn patients, multiple trauma patients, and patients undergoing major surgical operations often suffer from acquired immunologic deficits that predispose them to life-threatening sepsis. This paper reviews the current research in this area, with emphasis on identifying the components of the immune response affected by injury, elucidating the mediators of immunologic change, and determining new therapeutic approaches for correcting immunologic deficits. Lessons learned from the study of immune deficiency disease are reviewed, as are basic observations of burn- and trauma-induced immune depression. PMID- 3325509 TI - Anesthesia and the immune system. AB - While the direct effects of anesthesia on immunological competence have not yet been fully elucidated, it is clear that the use of certain anesthetics and anesthetic procedures contributes to reduced immune function, as demonstrated by such clinical markers as increased infection and tumor growth. This review evaluates evidence of the participation of anesthesia in suppression or activation of the immune system, and discusses the implications of these changes to patient care and outcome. PMID- 3325510 TI - Iron and immunologic function. AB - This short review focuses on the immunological functions of iron-containing compounds. Five such compounds--transferrin, haptoglobin, hemopexin, albumin, and lactoferrin--are thought to contribute to normal infection resistance. Experimental results that demonstrate the ability of these compounds to inhibit the growth of an important pathogen, Klebsiella pneumoniae, are discussed. PMID- 3325511 TI - Granulocyte kinetics in burns. AB - Granulocytes, predominantly polymorphonuclear neutrophils, are the major components of the body's defense against acute infections. Starting from pioneering work done 20 years ago by Alexander and coworkers, neutrophil dysfunction after major thermal injury has been well documented. Defects in neutrophil function have been recognized as being serum-borne. Additionally, a review of granulocyte function in burns was presented in 1984, at the Conference on the Immune Consequences of Thermal and Traumatic Injuries. Because of methodologic difficulties, however, our knowledge of granulocyte kinetics has increased very slowly. Although the bone marrow produces 1.5 billion granulocytes per kg body weight per day and the marrow granulocyte reserve is enormous, the hematopoietic tissues, along with the release, distribution, and possible role of granulocytes in the pathophysiology of burns, have not been studied thoroughly. This article presents a current review of our knowledge of granulocyte kinetics in burns and the production and possible fate of granulocytes in tissues. PMID- 3325514 TI - [The caudal lobe of the liver. Anatomical study. Surgical applications]. AB - The caudal lobe of liver is an independent sector astride the right and left liver regions. It is formed of two parts, right and left, distinguished exteriorly by the caudal and papillary processes, and can now be explored (ultrasound and CT imaging) allowing its surgical removal (tumoral lesion of the superior biliary confluent). PMID- 3325512 TI - Generation and activity of suppressor peptides following traumatic injury. AB - Severe trauma is known to produce pathophysiologic changes leading to the generation of immunosuppressive compounds. With recent advances in biotechnology, a number of these factors have been identified and characterized. Many of these substances have been found to be degradation products of normal serum and tissue proteins. These degradation products have profound biologic activity both in vivo and in vitro. This report briefly focuses on a number of these factors and summarizes the current work involved in the determination of the identity and mechanisms of a previously reported suppressor-active peptide isolated from the serum of trauma patients. PMID- 3325513 TI - Cyclosporine-induced long-term allograft survival and its potential in posttrauma tissue replacement. AB - This report is a partial review of our work to date concerning the use of cyclosporine and integumentary/musculoskeletal allografts for posttrauma tissue replacement. Our ultimate goals for such allografts are their lifesaving capabilities in addition to their utilization in functional and aesthetic surgical reconstructions. The potential for such a treatment regimen to produce anatomical replacement of lost parts is a primary motivating reason to pursue such studies. Permanent host-accepted integumentary/musculoskeletal allografts would appear to offer much greater promise in comparison with recent synthetic and cultured tissue replacements. Summarized topics covered in this review include short- and long-term use of cyclosporine in a 30% body surface area rat burn model; bacterial studies in this model; primary wound excision and use of cyclosporine in a massive 80% body surface area rat burn model; pathological skin alterations in cyclosporine-treated rats; the synergistic immunosuppressive effects of prior blood transfusions and cyclosporine; long-term residual cyclosporine levels assayed in various long-term surviving allograft-recipients; and the use of cyclosporine and cadaver skin allografts to treat massive full thickness burns in patients. PMID- 3325515 TI - [Pyosalpinx: anatomo-clinical experience and therapeutic inferences. Apropos of a retrospective study of 58 cases]. AB - Data from a series of 58 patients admitted with pyosalpinx, and representing 17.3% of cases of upper genital infections, were used to provide detailed information on therapy. Diagnosis was confirmed by celioscopy or laparotomy in all cases, and treatment essentially multiple antibiotic therapy by parenteral administration of wide spectrum compounds. Three subgroups of patients were distinguished: group 1 (15 cases) received immediate surgery due to severity of clinical picture or doubt as to diagnosis: in 54% the treatment was radical (hysterectomy-castration); group II (26 cases) received medical treatment only; group III (17 cases) underwent surgery after failure of medical treatment; operation was conservative in 52% of cases. Failure of medical treatment was related to a pyosalpinx volume of 8 cm3 or more in 86% of cases. No patient needed recovery surgery, while 3 had long term complications. Microbial flora was mainly anaerobic, diagnosis being dependent of celioscopy findings. Medical treatment alone allowed young women desiring pregnancy to conserve their genital apparatus in 44.8% of cases. When there is a lack of response to treatment, incomplete regression or recurrence then only surgery can be curative: the uterus and ovarian parenchyma should be conserved as far as possible because of new therapeutic perspectives. PMID- 3325516 TI - [False aneurysm of the superior mesenteric artery complicating a pancreatic pseudocyst. Report of a case and review of the literature]. AB - The authors report a case of a pancreatic pseudocyst complicated by a false aneurysm of the superior mesenteric artery. The diagnosis was made possible thanks to the evocative images of echography and C.T. scanning permitting to perform on time the arteriography. The surgical treatment consisted on the exclusion of the false aneurysm, which necessitated a distal bypass to revascularise the intestinal tract, and the drainage of the pseudocyst by a Roux en-Y loop. A review of literature is made. PMID- 3325517 TI - [Launois-Bensaude disease. Apropos of 2 new cases]. AB - Data relating to Launois-Bensaude disease are reviewed and two cases reported. Both patients were dyspneic, one of them presenting preoperative trachea deviation, a complication reported in only about 2% of cases documented in the literature. Dissection of these non-encapsulated fatty tumors is difficult and can lead to complications, but surgical excision remains the only possible treatment. PMID- 3325518 TI - [Utero-ovarian actinomycosis and intrauterine contraceptive devices]. AB - Up to now a rare affection difficult to diagnose in its abdominal localizations, actinomycosis is becoming of topical interest because of the appearance of a new form of the disease: utero-ovarian infection associated with an intra-uterine contraceptive device (IUD). A recent case, of surgical expression, is reported and used as a basis for an update of epidemiologic and pathogenic data concerning the affection. Diagnosis should be facilitated by regular cytobacteriologic examinations in women with the IUD, and simple preventive measures should limit the number of severe forms sometimes requiring more or less extensive excision. PMID- 3325519 TI - Scientific issues in the conduct of case studies. PMID- 3325520 TI - On the familial transmission of child psychiatric disorder. PMID- 3325521 TI - Concentrations of free and conjugated morphine in blood in twenty cases of heroin related deaths. PMID- 3325522 TI - [Problems in anti-leukemic drugs chemotherapy of childhood acute leukemia]. PMID- 3325524 TI - Prevalence and distribution of chromosome abnormalities in a sample of first trimester internal abortions. AB - Cytogenetic analysis was performed directly on villus material from 202 samples obtained at the evacuation of the uterine cavity in cases of retained abortion in the first trimester, identified as such by ultrasound examination. A precise delineation of the karyotype was obtained in 94% of the cases, while the efficiency of karyotype analysis in samples of spontaneous abortion was not higher than 50%. An abnormal chromosome constitution was found in 145 fetuses (76.7%) of which 117, including mosaics, were aneuploid (70%), 16 polyploid (8.5%) and 12 had structural abnormalities (6.3%). The relative proportion of chromosome abnormalities in this material is higher than that found in spontaneous abortion for trisomies and double trisomies, but lower for 45,X and polyploidy. The method was found to be efficient in obtaining fetal karyotypes also in those cases in which the villous material was scarce (1 mg), and thus it seems appropriate for routine cytogenetic studies in the first trimester abortions. PMID- 3325523 TI - HLA and TLX antigen expression on the human oocyte, zona pellucida and granulosa cells. AB - The expression of human leukocyte antigen (HLA) class I and class II molecules and one trophoblast-lymphocyte crossreactive (TLX) antigen by human oocytes and granulosa cells was investigated. Well-defined monoclonal antibodies directed against HLA class I and class II molecules as well as beta 2-microglobulin and a TLX molecule were used in a standard indirect immunofluorescence test and some immunogold techniques at the electron microscopic level. Single unfertilizable or multiply fertilized oocytes and granulosa cells obtained from an in-vitro fertilization programme as well as oocytes in primary, secondary and tertiary follicles of ovaries were studied. Neither HLA class I or class II molecules, nor beta 2-microglobulin, nor a TLX molecule were detected on cultured oocytes or oocytes in human ovarian follicles or in their zona pellucida. Granulosa cells taken from a culture medium and those in follicles at various stages of development expressed class I antigens, while granulosa cells from tertiary follicles also expressed HLA-DR antigens. These results confirm that the female human gamete belongs to that very small group of cells that lack major histocompatibility complex antigens. Since spermatozoa also lack HLA antigens, human germ cells are entirely different from other nucleated human cells with regard to the antigenic structures expressed on the cell surface. This would prevent recognition of these cells by the cellular immune system. Furthermore, HLA and TLX antigens are not involved in fertilization and early differentiation. PMID- 3325526 TI - Surgical management of longstanding temporomandibular joint ankylosis and resultant skeletal deformity. PMID- 3325525 TI - Tribute to Professor Friedrich Seidel on the occasion of his 90th birthday. PMID- 3325527 TI - Magnetic resonance imaging of the temporomandibular joint: preliminary work. PMID- 3325528 TI - Assessment of bite force: a review. PMID- 3325529 TI - Panic disorder and agoraphobia: fear of fear or fear of the symptoms produced by hyperventilation? AB - Two versions of the fear-of-fear hypothesis of panic disorder are discussed. The fear-of-the-somatic-effects-of-fear version, which is distinguished from the classical conditioning version, is compared with the hyperventilation theory of panic disorder and agoraphobia. The fear-of-the-somatic-effects-of-fear hypothesis is criticized on the basis of its inability to explain adequately (a) the initiation of panic attacks, (b) the growth in intensity of panic attacks, and (c) the termination of panic attacks. The tenability of the hyperventilation theory is supported by evidence from programs of treatment derived from the basic assumptions of the theory. PMID- 3325530 TI - Compartmental model analysis in pharmacokinetics. PMID- 3325531 TI - Verapamil and lithium in maintenance therapy of manic patients. AB - A year-long double-blind cross-over study was used to compare the long-term therapeutic effects of lithium versus verapamil in a group of 20 manic volunteers. Subjects received each medication for six months. Before cross-over, verapamil patients showed a significant improvement after 60 days, lithium treated patients after 180 days. After cross-over, verapamil-treated subjects showed improvement at day 240. Lithium-treated patients showed no improvement after cross-over. The data indicate that verapamil may be effective as an agent in the maintenance treatment of manic patients. PMID- 3325533 TI - The major histocompatibility complex and the Fugu aspect of immunity. PMID- 3325532 TI - Morphology and distribution of serotoninergic and oculomotor internuclear neurons in the cat midbrain. AB - Serotoninergic fibers have been reported in both the abducens and facial nuclei of the cat. Furthermore, serotoninergic dorsal raphe and oculomotor internuclear neurons occupy similar locations in the periaqueductal gray overlying the oculomotor and trochlear motor nuclei. To resolve the issue of whether these two populations of neurons overlap, serotoninergic fibers were assayed in the abducens and facial nucleus; then the morphologies and distributions of identified serotoninergic neurons and oculomotor internuclear neurons were determined. Both the abducens and facial nuclei contained varicosities labelled with antibody to serotonin, but a much higher density of immunoreactive fibers was present in the latter, especially in its medial aspect. Distinct synaptic profiles labelled with antibodies to serotonin were observed in both nuclei. In both cases, terminal profiles contained numerous small, predominantly spheroidal, synaptic vesicles as well as a few, large, dense-core vesicles. These profiles made synaptic contacts onto dendritic and, in the facial nucleus, somatic profiles that occasionally displayed asymmetric, postsynaptic, membrane densifications. Following injection of horseradish peroxidase into either the abducens or facial nuclei, double-label immunohistochemical techniques demonstrated that the serotoninergic and oculomotor internuclear neurons form two distinct cell populations. The immunoreactive serotoninergic cells were distributed within the dorsal raphe nucleus, predominantly caudal to the retrogradely labelled oculomotor internuclear neurons. The latter were located in the oculomotor nucleus along its dorsal border and in the adjacent supraoculomotor area. Intracellular injection of horseradish peroxidase revealed that oculomotor internuclear neurons have multipolar somata with up to ten long, tapering dendrites that bifurcate approximately five times. Their dendritic fields were generally contained within the nucleus and adjacent supraoculomotor area. In contrast, putative serotoninergic neurons were often spindle-shaped and exhibited far fewer primary dendrites. Many of these long, narrow, sparsely branched dendrites crossed the midline and extended to the surface of the cerebral aqueduct. In the vicinity of the aqueduct they branched repeatedly to form a dendritic thicket. The axons of the intracellularly stained serotoninergic neurons emerged either from the somata or the end of a process with dendritic morphology, and in some cases they produced axon collaterals within the periaqueductal gray. Thus the oculomotor internuclear and serotoninergic populations differ in both distribution and morphology.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325534 TI - Clinical characteristics of pigmented macules on palms and/or soles appearing after middle age in Japan. PMID- 3325535 TI - Incidence of friction melanosis in young Japanese women induced by using nylon towels and brushes. PMID- 3325536 TI - The mechanisms of histological incontinence of pigment: light and electron microscopic studies of lesions and patch test sites in female facial melanosis and DNCB reactions in guinea pigs. PMID- 3325537 TI - Ultrastructural sites of blister formation in dermatitis herpetiformis: report of a case and retrospective electron microscopy using routine histologic preparations. PMID- 3325538 TI - Cutaneous infection caused by Fusarium solani and Fusarium oxysporum. PMID- 3325539 TI - Microsporum ferrugineum infection with unusual clinical features. PMID- 3325540 TI - Systemic mastocytosis--case report and literature review. PMID- 3325541 TI - Erythema dyschromicum perstans/ashy dermatosis--a report of eight cases from Singapore. PMID- 3325542 TI - A new keratinolytic proteinase from clinical isolates of Trichophyton mentagrophytes. PMID- 3325543 TI - Dermatomal pruritus of the upper limb: a manifestation of nerve root compression due to degenerative spine disease? PMID- 3325544 TI - Update and future perspectives of a thymic biological response modifier (Thymomodulin). AB - Thymomodulin (Ellem Industria Farmaceutica spa, Milan, Italy) is a calf thymus acid lysate with immunomodulating activities. It is composed of several peptides with a molecular weight range of 1-10kD. Extensive studies in animal systems showed that Thymomodulin exhibited no, or very little toxicity even when used at high doses. Studies done in vitro and in vivo demonstrated that Thymomodulin is a biologically active compound which regulates the maturation of human and murine pre T lymphocytes, as well as modulate the functions of apparently mature human and animal B and T lymphocytes. It was observed that Thymomodulin can promote myelopoiesis as demonstrated by an increase of granulocyte-macrophage colonies in agar. Although additional studies to examine its target cell lineage are required, it appears that Thymomodulin exhibits specificity toward T cells. Therefore, enhancement of other cell lineage functions by Thymomodulin may be indirect, and mainly due to its effect on T cells. Of major importance is to note that Thymomodulin is prepared in a manner which allows it to maintain its biological activity when administered orally. PMID- 3325545 TI - Influence of heavy metals on the resistance of mice toward infection. AB - Previous studies have shown that heavy metals may exert marked immunomodulatory effects, at least in rodents, despite some discrepancies. However, the mechanism of their influence on the immune system is still unclear. As host resistance assays against experimental infections are generally considered as the most relevant criteria when predicting the immunotoxicity of drugs and chemicals, the effects of lead acetate, nickel chloride and sodium selenite on the resistance toward experimental Klebsiella pneumoniae infection was investigated in mice, with particular emphasis on the interference of the time of toxic exposure with the infectious challenge. Interestingly, one single intraperitoneal dose of 24 mg/kg lead or 4 mg/kg nickel enhanced the resistance of mice against Klebsiella pneumoniae when administered 24 hours before the infectious challenge, whereas host resistance proved to be impaired when the same dose was injected 5 hours after the infectious challenge. A 3-day pretreatment with 8 or 12 mg/kg lead also enhanced the resistance of mice but decreased it with 0.5 or 1 mg/kg nickel. In all cases, sodium selenite increased the resistance of mice toward infection. As lead, nickel and selenium appear to exert complex and possibly opposite effects on antibody response and phagocytosis, it remains to establish which immunotoxic consequences if any, an acute or chronic exposure to these heavy metals is likely to have in man. PMID- 3325546 TI - Enhanced hematopoietic recovery in irradiated mice pretreated with interleukin-1 (IL-1). AB - Data in this report compare the number of colony-forming cells (CFC) in bone marrow from irradiated and pre-irradiated C57Bl/6J mice injected with saline or recombinant interleukin-1-alpha (rIL-1). Eight to 12 days after sublethal or lethal irradiation, there were more CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units erythroid), GM-CFC (granulocyte-macrophage colony-forming cells), and day 8 CFU-S (colony-forming units-spleen) in bone marrow from rIL-1 injected mice than from saline injected mice. Prior to irradiation, there was no increase in number of CFC in bone marrow from rIL-1 injected mice. However, as determined by sensitivity to hydroxyurea, rIL-1 injection stimulated GM-CFC into cell cycle. These results demonstrate that rIL-1 injection increases the number of CFC that survive in irradiated mice and may be a consequence of the stimulation of CFC into cell cycle prior to irradiation. PMID- 3325547 TI - Hymenolepis citelli, H. diminuta and H. microstoma: immunoglobulin-containing cells in the lamina propria of the mouse gut during primary and secondary infections. AB - The indirect immunofluorescent technique was used to determine the occurrence of IgA, IgM and IgG1 immunoglobulin-containing cells in local intestinal mucosal immune responses to Hymenolepis citelli, H. diminuta and H. microstoma infections in mice. In the intestinal lamina propria of H. citelli and H. diminuta infected mice there was no increase in the mean numbers of immunoglobulin-containing cells when compared with uninfected control mice, but there was in H. microstoma infected mice. The numbers of IgG1- positive cells in both infected and uninfected mice were very small relative to IgA and IgM immunocytes. The distribution of immunocytes in the lamina propria of infected and uninfected mice was essentially similar and the localization of isotypes in duodenal sections showed no immunoglobulins in the villous epithelial cells. There was also no marked difference between primary and secondary infections indicating that immunoglobulin-containing cells play no major role in functional immunity against hymenolepid infections in the mouse. The presence of IgA and IgM was also demonstrated on the tegument of the tapeworms, although the distribution was patchy and more abundant on H. microstoma than on H. diminuta or H. citelli. The time of appearance of both isotypes was latest on H. citelli. PMID- 3325548 TI - Medical museum notes (Hon. Oliver Hampton Smith). PMID- 3325550 TI - Radionuclide scintigraphy in the diagnosis of small bowel disease. PMID- 3325551 TI - The pathophysiology of the juvenile bunion. AB - While the surgeon may tend to use one procedure in the repair of a hallux valgus deformity, versatility is most important when treating the juvenile bunion. Using a distal soft-tissue repair when subluxation is solely at the metatarsophalangeal joint is an acceptable approach. A metatarsal or cuneiform osteotomy is necessary if the intermetatarsal angle is abnormally large. It is important not to stretch the indications for a bunion technique in order to correct the hallux valgus deformity. If a more severe deformity is present, a more aggressive technique must be used to correct the abnormality. That varying success rates are reported with different techniques testifies to the fact that the juvenile bunion is not suited for a standard hallux valgus repair. The surgical technique used to repair a specific juvenile bunion depends upon the anatomic and physiologic abnormalities present in each patient. PMID- 3325549 TI - An evaluation of sucralfate in the treatment of peptic ulcer disease. A 'clinical real life study' of 54 patients in Indiana. PMID- 3325552 TI - Evaluation of fixation methods in cruciate ligament replacement. AB - Laboratory studies designed to simulate in vivo loading of a ligament graft and fixation method are affected by the age of the cadaveric donor, the types of tissue and fixation device employed, and the testing methods used. The use of older donors compromises the graft bone, underlying bone bed, and soft tissue. Staples, sutures, and screws all provide different fixation strengths depending on the tissue to be held. Cyclic testing of the graft better evaluates the performance of the composite during the activities of daily living, while high speed failure tests indicate the replacement's ability to resist a traumatic injury. Several studies were examined in light of these factors. Each study had certain merits but also limitations. Further studies are required for careful evaluation of the cyclic response of cancellous screws of different sizes, barbed staples, and other methods of graft fixation. Only then can recommendations be made as to the best device to use for achieving the clinical goals of joint stability, adequate resistance to traumatic loads, and proper graft attachment healing. PMID- 3325553 TI - Preoperative planning for high tibial osteotomy. PMID- 3325554 TI - The orthopaedic management of the ankle, foot, and knee in patients with cerebral palsy. AB - The surgical treatment of children with spastic cerebral palsy should be directed at all the problems of the child rather than focusing on one problem area at a time. Although the difficulties encountered by these children can be divided into separate areas for discussion, treating one problem without consideration of the others will result in unnecessary additional hospitalization for subsequent operations. In addition, since each joint is intimately linked to another, surgical treatment of one joint problem may lead to worsening of an adjacent joint deformity unless it too is addressed. Thus, the surgical care of the lower extremities in spastic cerebral palsy requires that the entire patient be evaluated and all necessary surgical procedures be coordinated. PMID- 3325555 TI - Bone structure and function. AB - Bone is a complex, living, constantly changing tissue. The architecture and composition of cancellous and cortical bone allow the skeleton to perform its essential mechanical functions. The stiffer cortical bone responds more slowly to changes in loads while cancellous bone has a much larger surface area per unit volume and a greater rate of metabolic activity. Periosteum covers the external surface of bone and consists of two layers: an outer fibrous layer and an inner more cellular and vascular layer. The inner osteogenic layer or cambium layer can form new bone while the outer layer forms part of the insertions of tendons, ligaments and muscles. The cortical bone of diaphyses and metaphyses has a dual blood supply that allows loss of one source of circulation without adversely affecting the viability of the tissue. Many epiphyses, even in adults, depend only on a single source of blood supply, the penetrating epiphyseal vessels. For this reason epiphyseal bone may infarct more easily than metaphyseal or diaphyseal bone. The bone matrix has an organic component, primarily type I collagen, which gives it tensile strength and an inorganic component, primarily hydroxyapatite, which gives it stiffness to compression. Specialized populations of bone cells form, maintain and remodel this matrix. We recognize four types of bone cells based on their locations, morphology and functions: osteoprogenitor cells, osteoblasts, osteocytes and osteoclasts. Osteoblasts develop from undifferentiated cells while osteocytes form from osteoblasts. Osteoclasts have a separate stem cell line, blood-borne monocytes. Bone matrix apparently attracts these monocytes and stimulates their differentiation into osteoclasts. The processes of bone modeling and remodeling require osteoclastic resorption of bone matrix and deposition of a new matrix by osteoblasts. Modeling shapes and reshapes bones during growth and stops at skeletal maturity. Physiologic remodeling does not change bone shape and consists of bone resorption followed by bone deposition in approximately the same location. Since it continues throughout life it appears to be important for maintenance of the skeleton, but its exact function remains obscure. Adaptive remodeling is the response of the bone to altered loads and may alter the strength, density and shape of bone. In recent years understanding of the control of bone cell function has increased significantly. The study of electrical effects on bone formation has lead to new treatments of nonunions and delayed unions. Physicians have applied understanding of matrix-induced bone formation to reconstruction of skeletal defects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325556 TI - Orthopaedic management of the lower extremities in spina bifida. AB - Myelodysplasia is a multisystem disease that requires a multidisciplinary approach. The orthopaedist is often the first to identify a changing neurologic picture or deformity and must work closely with neurosurgical colleagues to identify correctable neurologic lesions. The role of the orthopaedist begins at the birth of the child with spina bifida. At this time, the level of neurologic involvement can be determined. Education of the parents can then begin by outlining the expected ambulatory potential of the child, and predicting deformities or complications that might be anticipated depending on the level of neurologic involvement. The orthopaedist must also emphasize the extreme importance of neurosurgical care in preventing deterioration of neurologic function, so that goals for ambulation and musculoskeletal function can be achieved. As the child gets older, motor milestones paralleling those of a normal child should be sought with use of a corner chair or sitting device, followed by the use of a standing frame if needed. If appropriate, the child will then progress to full-control braces, with weaning as determined by neurologic level of involvement . Long-term mobility may be achieved by bracing or by the use of a wheelchair. A realistic approach must be taken in goal-setting, so that a child is not pressured to achieve unrealistic goals yet is enabled to achieve full functional capacity. PMID- 3325557 TI - Neuromuscular spine deformities. PMID- 3325558 TI - Longitudinal bone growth: the growth plate and its dysfunctions. PMID- 3325559 TI - Modern concepts in functional fracture bracing: the upper limb. PMID- 3325560 TI - Modern concepts in functional fracture bracing: the lower limb. PMID- 3325561 TI - External fixation of the upper extremity. AB - External fixation of forearm and arm fractures is an excellent treatment option, particularly in compound, comminuted fractures that result from high-energy trauma. Limb salvage and good function have been achieved in 75% of cases by applying the principles outlined. Problems with delayed bone union have been recognized and emphasize the importance of supplemental bone grafting. A number of external fixation systems are applicable to these upper limb fractures, and the authors have not found one system superior to the others. Open pin insertion is preferred, and pins (three proximal and three distal) are ideally placed near the fracture site for optimal stability. PMID- 3325563 TI - Soft-tissue injuries of the lower cervical spine. PMID- 3325562 TI - The nature of the mineral component of bone and the mechanism of calcification. AB - From the physical chemical standpoint, the formation of a solid phase of Ca-P in bone represents a phase transformation, a process exemplified by the formation of ice from water. Considering the structural complexity and abundance of highly organized macromolecules in the cells and extracellular tissue spaces of mineralized tissues generally and in bone particularly, it is inconceivable that this phase transformation occurs by homogeneous nucleation, i.e., without the active participation of an organic component acting as a nucleator. This is almost surely true in biologic mineralization in general. Electron micrographs and low-angle neutron and X-ray diffraction studies clearly show that calcification of collagen fibrils occurs in an extremely intimate and highly organized fashion: initiation of crystal formation within the collagen fibrils in the hole zone region, with the long axes (c-axis) of the crystals aligned roughly parallel to the long axis of the fibril within which they are located. Crystals are initially formed in hole zone regions within individual fibrils separated by unmineralized regions. Calcification is initiated in spatially distinct nucleation sites. This indicates that such regions within a single, undirectional fibril represents independent sites for heterogeneous nucleation. Clearly, sites where mineralization is initiated in adjacent collagen fibrils are even further separated, emphasizing even more clearly that the process of progressive calcification of the collagen fibrils and therefore of the tissue is characterized principally by the presence of increasing numbers of independent nucleation sites within additional hole zone regions of the collagen fibrils. The increase in the mass of Ca-P apatite accrues principally by multiplication of more crystals, mostly by secondary nucleation from the crystals initially deposited in the hole zone region. Very little additional growth of the crystals occurs with time, the additional increase in mineral mass being principally the result of increase in the number of crystals (multiplication), not size of the crystals (crystal growth). The crystals within the collagen fibers grow in number and possibly in size to extend into the overlap zone of the collagen fibrils ("pores") so that all of the available space within the fibrils, which has possibly expanded in volume from its uncalcified level, is eventually occupied by the mineral crystals. It must be recognized that the calcification of separate tissue components and compartments (collagen, mitochondria, matrix vesicles) must be an independent physical chemical event.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325564 TI - Osteoporosis: the structural and reparative consequences for the skeleton. AB - We have discussed the biomechanical and biomaterial properties of bone with emphasis on the microenvironment. The microdensity of bone tissues determines the resistance to compressive forces (strength = density2). The structural orientation of bone determines the ability of bone to withstand torsion and bending forces. Highly remodeled bone is brittle and fractures easily because of the multiple reversal planes within the bone plates. Conversely, augmentation of bone on the periphery by modeling leads to increased material microstrength and structural macrostrength. Consequently, appositional modeling augments whereas remodeling diminishes bone strength. Hip fractures, spinal fractures, Colles' fractures, and pelvic fractures have been discussed in terms of their pathophysiology and treatment. An algorithm (Fig. 4-7) has been presented for the differential diagnosis of patients with recently discovered spinal compression fractures. Lastly, a discussion of exercise demonstrated its beneficial role, especially in the retention of bone mass. PMID- 3325566 TI - [Left ventricular pseudoaneurysm after surgical treatment of ventricular septal rupture and left ventricular aneurysm complicated by acute myocardial infarction]. PMID- 3325565 TI - Benign and malignant cartilage tumors. PMID- 3325567 TI - [Valve replacement in infectious endocarditis with mycotic cerebral aneurysm]. PMID- 3325568 TI - [A case of recurrent left atrial myxoma]. PMID- 3325569 TI - [A case of intrathoracic multiple schwannoma and a review of the Japanese literature]. PMID- 3325570 TI - [Radical-free and highly reducible two dimensional polyacrylamide gel electrophoresis--application to the analysis of ribosomal proteins]. PMID- 3325571 TI - Workshop on Experimental Chemotherapy of Leprosy. Osaka, Japan, 11-20 November 1986. Dedicated to the memory of Dr. C.C. Shepard. PMID- 3325572 TI - Multiplication of Mycobacterium leprae in normal mice. PMID- 3325573 TI - Mouse breeding and husbandry. PMID- 3325574 TI - Application of the mouse foot-pad technique in immunologically normal mice in support of clinical drug trials, and a review of earlier clinical drug trials in lepromatous leprosy. PMID- 3325575 TI - Drug susceptibility testing of Mycobacterium leprae. PMID- 3325576 TI - Screening of drugs for activity against Mycobacterium leprae. PMID- 3325577 TI - The normal mouse in experimental chemotherapy. PMID- 3325578 TI - Pharmacokinetics in drug screening. PMID- 3325579 TI - Application of the thymectomized-irradiated mouse to the detection of persisting Mycobacterium leprae. PMID- 3325580 TI - The THELEP controlled clinical drug trials. Subcommittee on Clinical Trials of the Chemotherapy of Leprosy (THELEP). Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. PMID- 3325581 TI - Detection of persisting Mycobacterium leprae by inoculation of the neonatally thymectomized rat. PMID- 3325582 TI - The neonatally thymectomized rat as a model of the lepromatous patient. PMID- 3325583 TI - Multiplication of Mycobacterium leprae in the nude mouse, and some applications of nude mice to experimental leprosy. AB - Two aspects of the immune deficiency of nude mice make these animals particularly useful tools for leprosy research. Nude mice are capable of supporting multiplication of M. leprae to levels approaching 10(10) per g in peripheral body tissues. In addition, nude mice may be inoculated with greater than 10(4) (in fact, with as many as 10(8) organisms per foot pad, without provoking an immune response that prevents multiplication of the organisms. Thus, the nude mouse should be particularly suitable for detecting persisting M. leprae in treated patients, and as a model of the patient for evaluating chemotherapeutic regimens. PMID- 3325584 TI - Infection of other experimental animals with Mycobacterium leprae. PMID- 3325585 TI - [Observation of the superior mesenteric artery by ultrasonography: for prediction of the superior mesenteric artery syndrome]. AB - Superior mesenteric artery (SMA) syndrome is a major complication after scoliosis surgery. The author reports an ultrasonic observation of the SMA in normal and scoliotic individuals. There are three patterns of the SMA anatomy: Type I in which the SMA runs very close and parallel to the aorta, Type II in which the SMA branches off the aorta at a certain angle and Type III in which the SMA runs parallel to the aorta. Dynamic observation revealed that passage of food displaces the SMA anteriorly and to the left and that turning to the left from a supine position displaces the SMA from just anterior to the left of the aorta in normal individuals and from the right to the left side of the aorta in scoliosis cases. AMA itself has no significance in the occurrence of SMA syndrome because the SMA moves rather freely with the passage of food or position change. When this natural movement of the SMA is disturbed, one should carefully look for the possibility of SMA syndrome. PMID- 3325586 TI - [Therapy of foot deformities in spina bifida]. PMID- 3325587 TI - [Clinical studies on sarcoidosis]. PMID- 3325588 TI - [17 alpha-hydroxylase deficiency syndrome with hyperaldosteronism. A case report]. PMID- 3325589 TI - [An autopsy case of mycoplasma pneumonia in 81-year-old female associated with severe hemolytic anemia, multiple small lung abscess, disseminated intravascular coagulation and acute renal failure]. PMID- 3325591 TI - Kienbock's disease--the influence of arthrosis on ulnar variance determination. PMID- 3325590 TI - [A case report of giant retroperitoneal hemolymphangioma]. PMID- 3325592 TI - Experimental embryology as applied to the upper limb. PMID- 3325593 TI - Comparison of 1% lignocaine with 0.5% bupivacaine in digital ring blocks. AB - In a randomised double-blind trial comparing 1% lignocaine with 0.5% bupivacaine in digital ring block, the mean time of onset of complete anaesthesia was 5.8 minutes (range 5 to 10 minutes) for lignocaine and 11.2 minutes (range 8 to 20 minutes) for bupivacaine. The duration of action was 59.6 minutes (S.D. +/- 28.7 minutes) for lignocaine and 476 minutes (S.D. +/- 277 minutes) for bupivacaine. We describe how these differences can be exploited in clinical practice. PMID- 3325594 TI - Osteoid osteoma of the distal phalanx: a report of four cases and review of the literature. AB - Four cases of osteoid osteoma of the distal phalanx are described. The difficulty of diagnosis is stressed. Complete removal of the nidus is essential for surgical cure. Other modes of treatment are discussed and our series compared to other similar cases described in the literature. PMID- 3325595 TI - Osteoid osteomata of the distal phalanx. AB - Osteoid osteomata are rarely found in the distal phalanges of the hand. The 23 cases in the English language literature are discussed and two additional cases are described. The usual presenting features are chronic pain, nail enlargement and increase in size of the terminal part of the digit. Diagnosis is difficult but surgical excision is effective for treating the patients' pain. PMID- 3325596 TI - Richard J. Smith, M.D. 13 June, 1930-30 March, 1987. PMID- 3325597 TI - A hypothesis introducing a new calculation for discal reduction: emphasis on stenotic factors and manipulative treatment. AB - A literature review of the incidence and effects of manipulation on intervertebral disc protrusion is given. A case presented had a 14% reduction of the disc bulge following manipulative care with complete relief of sciatic and low back pain. A system to evaluate the size of disc herniation in computed tomography scans performed before and after manipulative treatment of disc protrusions is offered. Stenosis, with the critical compounded factors of vertebral canal size, dural sac cross-sectional area and soft tissue stenosis in protrusion of the ligamentum flavum and disc, as well as degenerative facet joint changes, is discussed to illustrate the complexity surrounding nerve root compression etiology. Understanding this integration of causative factors can help to explain low back symptoms and outline effective treatment plans. PMID- 3325598 TI - Michel Foucault and the philosophy of medicine. Introduction. PMID- 3325600 TI - The power of medicine, the power of ethics. AB - Foucault's genealogies and archeologies provide occasions in which one may come to know the powers, accidents, and influences that have structured a particular knowledge or discipline. The Birth of the Clinic shows the development of modern medicine in a process by which rational inference and emphasis on the history of a disease are replaced by pathological anatomy. In modern anatomy, the corpse, not reason, became the "space" of modern medical knowledge. In this "space" developed a confederation of dead body, knowledge, trained and noninferential gaze, organic unity, and the increased importance of bodily space instead of physical time. The discussion shows how Foucault's genealogy of modern medicine is influenced by and overcomes the knowledge that it describes. In this context, his genealogy is also shown to be self-overcoming and to raise important questions for medical ethics when ethical thought is conceived within the structures of knowledge that have been exposed by the genealogy. PMID- 3325601 TI - The place of space in The Birth of the Clinic. AB - This paper offers an account of the role of the concept of space in Foucault's The Birth of the Clinic, and, particularly, of the challenge it poses for conventional philosophical accounts of space and time. The question of the relation between conceptual, bodily, and institutional spaces is also treated. PMID- 3325602 TI - Confession and signification: the systematic inscription of body consciousness. AB - Formulas designed to reduce the overweight body flourish in American culture, yet 98% of all weight loss efforts end in failure. Numerous experts note that women, more frequently than men, are overweight and have greater difficulty adhering to reducing diets. I analyze the discourse of weight loss by taking up Foucault's concepts of confession and surveillance. Specifically, I argue that reducing techniques weave the language of science, deviance, and theology to fuel the perpetuation of a wholly transparent female subject. The weight conscious woman is divided within herself (mind versus body), and must, ironically, become and remain body conscious to alleviate body consciousness. Foucault's work, by describing the means by which bodies are inscribed in discursive practice, provides the diagnostic tools needed to assess the relation of dogma (reducing discourse) and individual (female body in need of alteration). PMID- 3325603 TI - Foucault's strategy: knowledge, power, and the specificity of truth. AB - This paper investigates the exemplarity of medicine in Foucault's analyses of knowledge generally. By tracing the development of his concept of power and its relation to knowledge, it offers an account of Foucault's unconventional philosophical project. Finally, it specifies Foucault's strategy for undermining processes of normalisation. PMID- 3325604 TI - An introduction to the medical epistemology of Georges Canguilhem: moving beyond Michel Foucault. AB - Although American philosophers and physicians are generally familiar with the writings of Claude Bernard (1813-1878), especially his Introduction to the Study of Experimental Medicine (1865), the medical epistemology of Georges Canguilhem, born in 1904, is virtually unknown in English speaking nations. Although indebted to Bernard for his conception of the methods to be employed in the acquisition of medical knowledge, Canguilhem radically reformulates Bernard's concepts of 'disease', 'health', 'illness', and 'pathology'. Contemporary exhortations to medical professionals and medical students that they "pay more attention to the whole patient" take on significance in working through the writings of Canguilhem; of crucial importance is the relation that obtains between a patient's unique symptomatology and the proper drug regiment that is required. PMID- 3325605 TI - Immunohistochemical demonstration of marked changes in the LHRH system of photosensitive and photorefractory European starlings (Sturnus vulgaris). AB - Immunocytochemistry was used to determine the effects of photoperiod on the LHRH neurosecretory system in the brain of male European starlings. In this species, as in other birds, reproduction is triggered by long daylengths but continued exposure leads to photorefractoriness and to a complete shut-down of the reproductive system. These effects are thought to be mediated through changes in the secretion of LHRH. In starlings exposed to a photoperiod of 11 h light:13 h darkness (11L:13D) and with fully developed testes there was strong immunostaining of both LHRH perikarya (n = 522 +/- 43 S.E.M.) and fibres. Photosensitive short-day (8L:16D) starlings with undeveloped testes had an almost identical distribution of strongly immunoreactive perikarya (n = 523 +/- 62) but there were fewer fibres. In the median eminence, fibre number was reduced significantly (P less than 0.01) by some 30%. In long-day (18L:6D) photorefractory starlings with fully regressed testes there was an even more obvious change in the LHRH system. Perikarya were only weakly immunoreactive and there was a significant (P less than 0.01) reduction in mean diameter from 10 to 6.5 micron. In addition, there was a significant (P less than 0.05) reduction in cell number (312 +/- 62), although this may well result from the fact that some weakly stained cells fell below the limits of resolution and could not be counted. LHRH fibres disappeared almost entirely from the median eminence, and were not visible elsewhere in the brain. The higher neural pathways regulating photorefractoriness induced by long days are unknown but clearly both production of LHRH in the perikarya and release/storage of LHRH in the terminals is being profoundly modified. PMID- 3325606 TI - Effect of low temperatures on glucose-induced insulin secretion and ionic fluxes in rat pancreatic islets. AB - The direct effect of cold on the inhibition of B cell secretion is well known in hibernating and experimentally hypothermic mammals. This temperature dependency may result from the inhibition of ion transport across the membranes. In order to verify this hypothesis, ionic effluxes and insulin secretion from rat islets loaded with 86Rb+ and 45Ca+ were measured during perifusion. At 37 degrees C, the rise in glucose concentration from zero to 16.7 mmol/l provoked a rapid decrease in 86Rb+ efflux, an early fall and subsequent rise in 45Ca2+ efflux and a typical biphasic pattern of insulin secretion. At 27 degrees C, glucose induced only a very slight increase in insulin secretion, while the fluxes of radioactive ions were not significantly modified in amplitude but were clearly delayed. At 17 degrees C, no insulin response to glucose was observed and the decrease in K+ conductance indicated by 86Rb+ flux decrease was less temperature-dependent than the movement of Ca2+. After supplementary stimulation with a high extracellular concentration of Ca2+, insulin secretion was enhanced at 27 degrees C and reached levels induced by glucose alone at 37 degrees C. An increase in hormone secretion occurred even at 17 degrees C, but only during a first phase of secretion. Regular increases in temperature potentiated insulin secretion and provoked changes in ionic fluxes which suggest that B cell depolarization (86Rb+ flux decrease) induced by glucose can occur at 15 degrees C but cannot induce the opening of voltage-dependent Ca2+ channels (increase in 45Ca2+ efflux) until temperatures higher than 27 degrees C are reached.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325607 TI - Effect of thyroid hormones on angiotensinogen production in the rat in vivo and in vitro. AB - The influence of thyroid hormones on angiotensinogen production was studied in vitro and in vivo. In the in-vitro system, angiotensinogen production rate (APR) of monolayer cultures of rat hepatocytes in response to tri-iodothyronine (T3) and thyroxine (T4) was assayed. In the in-vivo system, plasma angiotensinogen concentration (PAC) and liver angiotensinogen content (LAC) were measured in hyper- and hypothyroid rats. In both thyroid dysfunctions, a significant decrease of PAC was found compared with that in control animals; however, LAC showed a significant increase in hyperthyroidism and a marked decrease in hypothyroidism. As PAC is dependent upon both angiotensinogen production by the liver and angiotensinogen degradation by renin, the decrease in PAC observed in hyperthyroidism could be due to an increase in plasma renin concentration, which would overcome the increased synthesis of liver angiotensinogen observed in these animals. In fact, addition of various concentrations of T4 or T3 to monolayer cultures of adult rat hepatocytes significantly enhanced APR. This increase was greater and started earlier with T3 (1196.1 +/- 143.7 (S.D.) pg/mg protein per 6 h incubation; significant differences at the third hour of incubation) than with T4 (858.3 +/- 88.2 pg/mg protein per 6-h incubation; significant differences at the sixth hour of incubation). In addition, a close dose-response relationship was found in the cultures supplemented with T3. The different time-course in the response elicited by T3 and T4 on APR could be a consequence of the necessary transformation of T4 into T3 to acquire biological activity. PMID- 3325608 TI - Sex differences in the LH responses to chicken LHRH-I and -II in the domestic fowl. AB - Maximal incremental changes in plasma LH were compared in adult hens and cockerels after i.v. injection of chicken (c) LHRH-I (pGlu1-His2-Trp3-Ser4-Tyr5 Gly6-Leu7-Gln8-Pro9-Gly10-N H2) or cLHRH-II (pGlu1-His2-Trp3-Ser4-His5-Gly6-Trp7 Tyr8-Pro9-G ly10-NH2). The LH response to cLHRH-I and -II was more rapid and greater in cockerels than in hens. The potencies of the two decapeptides were the same in cockerels but different in hens. Relative to cLHRH-I, the potency of cLHRH-II was 0.91 (0.6-1.2; 95% confidence limits) in cockerels and 36.5 (16.8 128.6) in hens. The greater potency of cLHRH-II relative to cLHRH-I in the hen than in the cockerel could not be accounted for by sex differences in the half lives of the decapeptides in the peripheral circulation. The half-lives of both decapeptides in hens and cockerels ranged between 2.42 and 3.77 min. It is concluded that the interaction between LHRH-I and -II and the gonadotrophs is sexually differentiated in the domestic fowl. A new homologous radioimmunoassay was established for cLH. As in other chicken LH radioimmunoassays, there was evidence of cross-reactivity with TSH. PMID- 3325609 TI - Pulsatile administration of luteinizing hormone releasing hormone (LHRH) for inducing ovulation. PMID- 3325610 TI - Sonographic patterns of abdominal lymphoma. PMID- 3325611 TI - Splenic hamartoma: report of a case and review of the literature. PMID- 3325612 TI - [Fatal multiple pterygium syndrome and nuchal hygroma]. AB - A turkish family with three sibs (including twins) affected by the lethal multiple syndrome is reported. PMID- 3325614 TI - Anticandidal activity of eupolauridine and onychine, alkaloids from Cleistopholis patens. PMID- 3325613 TI - Antimalarial agents, 4. Synthesis of a brusatol analog and biological activity of brusatol-related compounds. AB - The quassinoids bruceoside-A [1], brusatol [2], and bruceolide [3] were tested for antimalarial activity in vitro against the chloroquine-resistant (Smith) isolates of Plasmodium falciparum. Compound 2 was quite active, 1 was not active, and 3 showed only a trace of activity. The fact that 15 [(E)-non-2-enoyl] bruceolide [7] synthesized from 2 was eight times less active than 2 would indicate that the requirement of a C-15 ester moiety for enhanced antimalarial activity among brusatol related quassinoids could be quite specific. PMID- 3325616 TI - Migrainous olfactory hallucinations. AB - Three patients with olfactory hallucinations related to migraine are described. PMID- 3325615 TI - Oligodendroglioma occurring after radiation therapy for pituitary adenoma. AB - A 38 year old male dentist developed an oligodendroglioma of the left medial temporal lobe and parasellar region 12 years after radiotherapy with 6600 rads of acromegaly. The 30 cases of radiation-induced gliomas reported in the English literature are reviewed and analysed. The criteria for defining radiation-induced tumours of the central nervous system are proposed as follows: the tumour has a long quiescent "latency period", a location in the previously irradiated field, a verified histological difference from a primary condition, and does not arise from a primary condition associated with a genetic syndrome such as neurofibromatosis or tuberous sclerosis. The reported case fulfilled these criteria but appears to be the only reported radiation-induced oligodendroglioma. PMID- 3325617 TI - Recovery from myocardial infarction: a review of psychosocial determinants. PMID- 3325619 TI - Types of patients with crowns in general dental practices. AB - Based on data from patient records of 9996 crowns constructed in forty general practices, it is discussed what crown types have been constructed in different patient categories. It was found that female 'crown patients' received on average more crowns than male patients. Hardly any difference was found between the average number of crowns the patients with or without reimbursement had received. In the younger patients (less than 21 years) more jacket crowns were constructed. The 21-30 year group received more full metal crowns, whereas the oldest group (greater than 51 years) had more metal-porcelain crowns. Sick-fund patients received more jacket crowns and metal-porcelain crowns on front teeth, while private patients received more full-metal crowns. PMID- 3325618 TI - Edentulousness--an oral handicap. Patient reactions to treatment with jawbone anchored prostheses. AB - A questionnaire was sent to all 189 edentulous patients with denture adaptation problems who were treated with fixed prostheses on osseointegrated oral implants during the period 1965-1978. One hundred and fifty-two patients (80%) responded. Practically all had adapted well to the prostheses and were most satisfied with the rehabilitated oral function, including chewing ability. Four out of five patients regarded the bridge as part of their own body instead of a foreign object, and 90% would not hesitate to have the treatment performed again, if necessary. Parallel with the improved oral function the patients reported a definite reduction of psychosocial problems associated with their previous oral invalidity, and increased security and self-esteem. PMID- 3325620 TI - The nematode's cuticle--its surface and the epidermis: function, homology, analogy--a current consensus. PMID- 3325621 TI - Struvite precipitation by Trypanosoma cruzi. PMID- 3325622 TI - Ultrastructural localization of protective and nonprotective Plasmodium falciparum proteins using serum samples from vaccinated Aotus monkeys. AB - Postembedding immunoelectron microscopy, using pooled serum samples from a recent vaccination experiment involving Aotus monkeys, was used to localize immune targets in Plasmodium falciparum-infected erythrocytes and free merozoites. Serum samples from Aotus monkeys, protected completely by immunization with the P. falciparum merozoite surface coat precursor protein, identified immune targets on the surface of free and intracellular merozoites as well as the cytoplasm, plasma membrane, and parasitophorous vacuole membrane of immature schizonts. Serum samples from unprotected monkeys, which had been immunized with a complex of 143 kDa, 132-kDa, and 102-kDa polypeptides reacted specifically with the rhoptries of immature schizonts and mature merozoites. PMID- 3325623 TI - Wheat germ agglutinin specifically binds to the surface of infective larvae of Wuchereria bancrofti. PMID- 3325624 TI - A rapid method for screening antibodies to Plasmodium yoelii liver stages by immunofluorescence. PMID- 3325625 TI - The role of rat C3 and C3 receptor-bearing alveolar macrophages in in vitro attrition of infective larvae of Nippostrongylus brasiliensis. PMID- 3325626 TI - Predation of cattle fever ticks by hispid cotton rats in south Texas. PMID- 3325627 TI - The effect of membrane filtration upon protein conformation. PMID- 3325628 TI - Induction of protection against candidiasis in tumor-bearing mice by vaccination with Candida albicans ribosomes. AB - The aim of this study was to determine whether vaccination of tumor-bearing mice with ribosomes of Candida albicans would result in the induction of protective immunity. Therefore, (BB)F1 mice were inoculated intraperitoneally with the thymoma, EL-4, then immunized with ribosomes purified from C. albicans, and challenged intravenously with C. albicans to assess the protective response. Unimmunized mice, both normal and tumor-bearing, treated in the same manner served as controls. Both normal and tumor-bearing mice developed protective immunity in response to immunization with ribosomes. The protected mice had fewer colony-forming units in their kidneys 3 days after intravenous challenge than the unimmunized control animals, regardless of tumor status. Moreover, all unimmunized mice, tumor-bearing and normal, developed delayed hypersensitivity to the ribosomes, as well as ribosome-specific antibody, both of which were of the same order of magnitude. Therefore, the EL-4 thymoma does not suppress the immune system of mice, and they are capable of responding immunologically in a normal manner to C. albicans. PMID- 3325629 TI - Evaluation of a test to detect circulating Aspergillus fumigatus antigen in a survey of immunocompromised patients with proven or suspected invasive disease. AB - An ELISA for the detection and measurement of Aspergillus antigenaemia has been developed and evaluated by examining sera submitted over a 12-month period from immunocompromised patients with a likelihood of invasive aspergillosis. Results from proven cases of invasive aspergillosis confirmed at post-mortem and specimens from individuals with suspected disease showed that tests on single serum samples were often negative. Multiple specimens from the same patient greatly increased the frequency of detection. Repeated monitoring of sera from a single patient showed wide fluctuations in antigen level, which was considered to be due partly to the medical regimen to which the patient was subject. Control sera from healthy laboratory personnel were consistently negative, but a number of 'at-risk' patients without other evidence of invasive aspergillosis sometimes had low amounts of antigen. Concentrations of Aspergillus antigen of 100 ng ml-1 or higher were considered to be strongly suggestive of fungal invasion. PMID- 3325630 TI - Inhibition of phagocyte migration and spreading by spore diffusates of Aspergillus fumigatus. AB - Previous studies have shown that spores of Aspergillus fumigatus inhibit phagocytosis and killing by macrophages and polymorphonuclear leucocytes. In order to identify the mechanisms of this interference with host defences, we have examined the effects of A. fumigatus spore diffusates on phagocytic cell function. For comparison, we have used spore diffusates of the non-pathogenic fungus Penicillium ochrochloron. The diffusates of A. fumigatus reduced the number of human polymorphonuclear leukocytes migrating towards a known chemoattractant by approximately 50% (p less than 0.001). In addition spore diffusates of A. fumigatus significantly decreased (p less than 0.001) the capacity of primed mouse peritoneal exudate cells to spread on glass. Spore diffusates of P. ochrochloron showed no comparable inhibitory effects. These studies have shown that spore diffusates of A. fumigatus inhibit the movement of the phagocytic cell membrane and are thus able to interfere with a primary function of phagocytic cells. PMID- 3325631 TI - Nasal phaeohyphomycosis caused by Bipolaris hawaiiensis. AB - A bilateral nasal phaeohyphomycotic infection caused by Bipolaris hawaiiensis in an immunocompromised woman from India is described. Repeated direct microscopic examinations of the nasal scrapings revealed the presence of septate, branched, pigmented hyphal fragments intermingled with cells that divided internally by one transverse septum and a few cells that were chestnut brown dividing internally by septa in different planes to become muriform. Cultures of the scrapings yielded B. hawaiiensis. Local excision of the crusted lesion followed by application of 0.03% nystatin solution four times a day for 3 weeks cured the infection. PMID- 3325632 TI - Extracellular iron chelation in Cryptococcus neoformans. AB - Low-iron minimal medium supported growth of Cryptococcus neoformans but spent medium contained no hydroxamates, organic acids or other iron chelators. Exogenous deferoxamine stimulated growth in extreme iron-limitation, while neither organic acids nor quartersaturated transferrins were stimulatory. These results suggest two iron uptake mechanisms, one dependent upon exogenous hydroxamate, the other hydroxamate-independent. PMID- 3325633 TI - Incidence and prediction of periventricular-intraventricular hemorrhage in very preterm infants. AB - During a prospective national survey of mortality and morbidity in infants born before 32 weeks gestation in the Netherlands in 1983, the incidence of periventricular-intraventricular hemorrhage (PIVH) was studied with ultrasound, in 484 of those infants. Stepwise logistic regression analyses were used to examine the predictive value of several maternal, prenatal and postnatal factors for the development of neonatal PIVH. PIVH was detected in 140 infants (28.9%); of these, 36 were grade I, 39 grade II, 22 grade III and 43 grade IV. The mortality rate increased from 3 to 84% with increasing severity of PIVH. Gestational age appeared to be the strongest predictive factor for both incidence and severity of PIVH, followed by idiopathic respiratory distress syndrome (IRDS), prolonged rupture of membranes and birth weight. Of the maternal and prenatal factors studied, only prolonged rupture of membranes (greater than 24 hours) and preeclampsia appeared to influence the risk of developing PIVH. Both were associated with a 50% reduction in the incidence of PIVH. None of the intrapartum factors studied showed a significant association with subsequent development of PIVH. Development of IRDS appeared to result in a twofold increase in the incidence of PIVH. PMID- 3325634 TI - Transcutaneous fetal Pco2 monitoring during labor--an introduction to the EEC multicenter trial. PMID- 3325635 TI - The European Community Project "Perinatal Monitoring". PMID- 3325636 TI - Measurement and processing of fetal transcutaneous Pco2 levels. AB - Because asphyxia is not the only factor influencing fetal heart rhythm, a non optimal cardiotachogram is not necessarily a sign of fetal distress. It makes further evaluation of the fetal condition advisable, especially determination of the acid-base equilibrium. The method of fetal blood sampling, introduced by Saling, has a number of disadvantages for mother and fetus, because of the invasiveness for both. Further, the measured acid-base equilibrium is only representative for a very short period of time and often repeated micro-blood sampling is necessary. A major problem with regard to determination of the acid base equilibrium in intermittently obtained fetal blood samples is the inclusion of air bubbles in the sample. When they are introduced into the electrode cuvettes, the measured values cannot be considered reliable. The problem was solved in the Department of Obstetrics and Gynecology of the Vrije Universiteit of Amsterdam with a "pipe" shaped special collecting vessel. Similar measuring results were obtained with the formerly used glass capillary method and the special collecting vessel method. Continuous, non-invasive methods have been pursued to avoid the above mentioned problems. Fetal transcutaneous Po2 measurement has been possible for years, but does not provide adequate information during the important second stage of labor because of methodological problems. Continuous fetal tissue pH surveillance is possible, but it also has an invasive character and is technically difficult to perform, leading to many methodological failures. Recently, continuous transcutaneous Pco2 measurement tcPco2 became available. A good correlation was found with simultaneously measured Pco2 levels in fetal blood samples and with those of umbilical artery blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325638 TI - Clinical experience on tcPco2 during labor. AB - tcPco2 measurements in the fetus during labor were evaluated by analysing the clinical experience in 224 cases. This additional mode of supervision was performed in combination with continuous cardiotocography (CTG) and intermittent fetal blood sampling (FBA) in cases with suspect, prepathologic or pathologic heart rate patterns. The prechosen measuring temperature was 39 degrees C in 105 and 44 degrees C in 119 cases. The normal range of the tcPco2 was defined by calculating the mean value and two standard deviations in cases without hypoxic complications. The absolute values of the normal range were different according to the measuring temperature, when no correction factor was used. After adjusting the transcutaneous values to the blood gas level by means of the Severinghaus formular no significant differences in the tcPco2 values were notified for the two applied temperatures (39 degrees C and 44 degrees C). There is an obvious rise of tcPco2 with the progress of labor. Comparing the tcPco2 values with the pH values in the fetal blood we found a statistically significant correlation at either temperatures (p less than 0.001). Aiming at an early detection of raising acidity in the fetal blood, an action line of 55 mmHg after correction (80 mmHg at 44 degrees C, 63 mmHg at 39 degrees C) is an adequate basis for clinical intervention as all acidotic (pH less than 7.20) and the majority of preacidotic value (pH 7.20-7.24) can be excluded. One clinical benefit that can be expected by the additional use of tcPco2 is the reduction in the necessity of fetal blood sampling in a number of cases with abnormal heart rate patterns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325637 TI - Glue fixation of the tcPco2 electrode for fetal monitoring. AB - tcPco2 monitoring on the fetal scalp potentially is a beneficial and additional new tool for the surveillance of the unborn child. During a clinical trial we investigated the tcPco2 monitoring using the glue fixation technique. A modified Severingshaus electrode was applied on a prepared area on the fetal scalp by means of an endoscope. The attempt of application was successful in 224 out of 245 cases, while reapplication was only necessary in 8 cases. The accuracy of the tcPco2 measurement using glue fixation was sufficient at both measuring temperatures (39 degrees C and 44 degrees C). The correlation coefficient comparing the data with the tcPco2 of the fetal blood was 0.74 respectively 0.81. The development of a caput succedaneum leads to higher absolute values of the tcPco2. When a caput succedaneum has developed in the measuring area the mean value of the tcPco2 is significantly higher (62.70 mmHg instead of 55.14 mmHg respectively 68.98 mmHg instead of 65.98 mmHg) at 39 degrees C respectively 44 degrees C. No significant influence of different preparation techniques of the measuring site has been found during this investigation. The glue fixation technique leads to a reliable recording of tcPco2 in the fetus during labor, when the electrode is placed in a central and not compressed position on the lower pole of the fetus. The disadvantage is the necessity of extensive training of the personnel and the large number of instruments, factors that will interfere with a more widespread use in clinical routine. PMID- 3325639 TI - Seronegative rheumatoid arthritis and HLA-DR4: proposal for criteria. PMID- 3325640 TI - The arthritis of brucellosis: a perspective one hundred years after Bruce's discovery. PMID- 3325641 TI - Silicone synovitis. PMID- 3325643 TI - Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. AB - Methotrexate pneumonitis is emerging as one of the most unpredictable and potentially serious adverse effects associated with the use of low dose, pulse methotrexate in treating rheumatoid arthritis (RA). We report 4 new cases of methotrexate pneumonitis in patients with RA and review 6 published cases. A greater than expected proportion of patients had a smoking history, preexisting pulmonary disease and were male. Prognosis was better in those patients treated with corticosteroids. PMID- 3325642 TI - Adult Still's disease: review of 228 cases from the literature. AB - To clarify the clinical pictures of adult Still's disease, 228 cases reported in the past 15 years since Bywaters' first description were reviewed. These included our 9 new cases and an additional 25 cases from the Japanese literature, none of which had been described in previous English reviews. Most of the patients with long followup showed frequent recurrences. About one third developed deforming arthritis with ankylosis. There were 6 deaths. Of interest was the remarkably elevated levels of serum ferritin and prostaglandin E1 in some patients. PMID- 3325645 TI - A microcomputer-based procedure for carrying out rhinomanometry. AB - The determination of nasal airway resistance by the technique of anterior rhinomanometry is made difficult by several factors. Among these are the variability in the breath by breath measurement of airflow and pressure, the effect of under or over breathing, and the ability to produce a smooth transition between inspiration and expiration during which period the measurements are made. To overcome some of these problems a standard procedure has been developed (in our laboratory) for active anterior rhinomanometry. The nasal resistance is calculated from the mean of three sets of three readings with a rest interval between each set. To enable the procedure to be carried out with consistency it has been implemented on a BBC microcomputer. This enables a breathing guide to be provided for the subject, as well as providing a display of each flow pressure curve, a display of the mean curve, plus and minus one standard deviation, and the calculation of left, right and total nasal airway resistance. PMID- 3325644 TI - A review of medical applications of magnet attraction and detection. PMID- 3325646 TI - Research on mental handicap, 1957-1987: a selective review. AB - Some of the major advances in research over the last 30 years are outlined. While primarily offering an account of the behavioural sciences as applied to this field, some attention is devoted to major biomedical findings which have revolutionized our potential for preventive action. Mental handicap research has been a powerful influence in changing practices. PMID- 3325647 TI - Cognitive psychology and mental handicap. AB - The psychology of mental handicap has been influenced by two traditions in general psychology, pychometric measurement following Binet and experimental psychology first initiated by Wundt. The weakness of the former is its lack of explanatory power and, of the latter, its lack of sound alignment with the neuropathology of mental handicap. A closer association of experimental psychology and neuropathology might help us to reframe our concepts of intelligence, cognitive functions and their handicaps. PMID- 3325648 TI - The American mental retardation service system. AB - Significant changes have occurred in the United States in the last 30 years relative to the delivery of services to mentally retarded people. This paper explores the development of community service options in the United States since the late 1950s. The development of these new services is viewed relative to concerns with both deinstitutionalization and normalization. From the vantage point of the mid-1980s, the paper also explores the importance of information on the continuum of care cycle of mentally retarded individuals throughout the life cycle as an important guide to the understanding of how the American mental retardation service system functions. PMID- 3325649 TI - Development, disintegration and dementia. AB - It has been argued that there is an important group of conditions, seen for the first time in late infancy and early childhood, which are both remarkably persistent and pervasive in their influence on cognitive and social development. They combine features of childhood autism, mental retardation and cognitive deterioration and the term 'disintegrative' most precisely characterizes their impact on development. The term 'psychosis' is only usually appropriate in describing the severity of the psychiatric symptoms. In order to avoid confusion with the psychoses or dementia of adult life, the term 'disintegrative disorder of development' may be preferred. While specific pathology is being identified in an increasing number of cases, the combined use of psychiatric and physical diagnostic categories perhaps best serves to draw attention to this important group of disorders. It is likely that, with increasing knowledge, the need for such an interim diagnostic category may become unnecessary. PMID- 3325650 TI - Epidemiological issues in mental retardation. AB - The basic epidemiological issues have not changed fundamentally in 30 years but emphases are different. Clarity of concept and definition is essential; we need several definitions for different purposes, and should distinguish global criteria defining groups in some way specifically 'retarded' and partial criteria defining groups not exclusive to retardation. Of global definitions, we can distinguish Intellectual Impairment based on IQ, Learning Disability based on educational criteria, and Mental Handicap or Retardation based on service or administrative criteria. The first and second may be co-terminous for children. The first and third are usually co-terminous below a certain IQ level, conventionally 50, as SII and SMH/R. This is not so for higher ability groups: MII and MMR are conceived and defined differently, and suit different research purposes. There may be much unknown need because there have been so few studies of total IQ defined groups above 50. Although organic and psychological factors are very important, the study of MMR needs to recognize its primarily social nature, reflecting determinants of selection into MMR status in legal, organizational and professional structures, activities and attitudes characteristic of particular communities and cultures. If the primary focus is on aetiological factors, natural history, and preventive possibilities, study group should be aetiologically defined and preferably not limited to MR. The same applies to specific impairments, disabilities, diseases, behaviours and disadvantages. The services are also susceptible to epidemiological approaches, descriptive, analytic, interventionist and evaluative, but little is yet available on agency structure and function, professional activities, attitudes and training, legal contexts, and financial constraints. Rigorous outcome studies would greatly benefit rapidly developing services. We know quite a lot about the distribution and associations of SII/SMR, though more is needed, especially to clarify issues of social class distribution. There is a dearth of good research in MII or MMR, and several large scale new studies could be justified. Work on the epidemiology of aetiological entities has progressed, though there are many gaps. Because of their rarity, we should be looking to bring together all the data on aetiological diagnosis now accumulating in good paediatric units throughout the UK. PMID- 3325651 TI - The effect of doxorubicin (adriamycin) on cytoplasmic microtubule system in cardiac cells. AB - The objective of this study was to determine whether the antineoplastic agent doxorubicin (adriamycin) affects the microtubule system in isolated cardiac cells. Embryonic chick heart cultures were exposed to adriamycin concentrations of 40, 80, or 200 microM for 3, 12, or 24 h before fixation prior to immunofluorescence. Adriamycin produced marked distortions in the normal microtubule system. This was a function of adriamycin concentration and the duration of the exposure to adriamycin. Even when adriamycin was removed from the medium for a 12 h period, cells treated with adriamycin showed abnormalities of the microtubule system. The effect of adriamycin on the microtubule system extends to its reassembly after colchicine. Cells allowed to recover after colchicine in the presence of adriamycin (40 microM) showed impairment in microtubule regeneration. These data indicate that the microtubule system in cardiac myocytes is affected by adriamycin both by damaging microtubule structure and by impairing microtubule reassembly. PMID- 3325652 TI - Neurochemical analysis of single neurons: a mini-review dedicated to Oliver H. Lowry. PMID- 3325653 TI - The AIDS epidemic and the drug substance abuse patient. PMID- 3325654 TI - Emotional aspects of AIDS--implications for care providers. PMID- 3325655 TI - The relationship of addiction, tolerance, and dependence to alcohol and drugs: a neurochemical approach. AB - Alcohol and drug addiction are defined in behavioral terms as the preoccupation with, compulsive use of, and relapse to drugs that are descriptive and confirmatory. The basis of addiction may involve neurochemical changes in the brain that distort and redirect the drive states (instincts). Tolerance and dependence may only be incidentally associated with addiction as a result of a nonspecific adaptation by the body to the presence of a drug. The cellular adaptation may be the same in all organs. Addiction to alcohol and drugs may have no specific relationship to tolerance and dependence. Addiction occurs in the absence of observable tolerance and dependence to alcohol and drugs. Alcohol and drug addiction is probably more complex than tolerance and dependence. Addiction is difficult to study because of the variability of behavioral phenomena and the underlying intricacies of the neurosubstrates. Tolerance and dependence are still useful as they are indicators of drug use. It is a misconception that long term chronic use is necessary for tolerance and dependence to develop. Some studies have shown that tolerance can develop within hours and days to a single dose of alcohol or other drugs. Anxiety, depression and insomnia can occur after a single dose of ethanol in humans. These symptoms of withdrawal from the alcohol or drug constitute dependence. Redefining the criteria for addiction tolerance and dependence to alcohol and other drugs may be in order. A neurochemical model may provide a more definitive and uniform basis for considering addiction, tolerance, and dependence to alcohol and drugs. PMID- 3325656 TI - Effects of calcium loading in DOCA-salt hypertensive rats. AB - The effects of oral calcium loading on blood pressure (BP) of DOCA (deoxycorticosterone acetate)-salt hypertensive rats (D-S rats) were investigated. Calcium loading was performed by adding 1% CaCl2 (calcium chloride) to the drinking water. Calcium loading attenuated the development of high BP in D S rats, and at the end of a two week experiment, BP was 141 +/- 3 (calcium treated) vs. 174 +/- 7 mmHg (non-calcium treated) (p less than 0.01). However, calcium loading did not cause any changes in BP in normotensive rats. Further, in established D-S rats [after four weeks of DOCA and 1% NaCl (sodium chloride) treatment], calcium loading for 4 weeks also reduced BP [144 +/- 6 (calcium treated) vs. 181 +/- 4 mmHg (non-calcium treated), p less than 0.01, at the end of experiment]. With calcium treatment, there were no significant changes in sodium-water balance, plasma levels of epinephrine and norepinephrine, plasma renin activity, plasma aldosterone concentration and serum electrolytes both in developing and established D-S rats. The depressor mechanism of calcium loading was studied by observing vascular responsiveness to norepinephrine both in whole body and in hind limb preparations. Vascular reactivity in both developing and established D-S rats was significantly attenuated by calcium treatment. These results suggest that the antihypertensive effects of calcium treatment in D-S rats are mainly caused by attenuation of vascular reactivity. PMID- 3325658 TI - [Cyclosporine in allogeneic bone marrow transplantation in children]. PMID- 3325659 TI - [A case of refractory anemia complicated by pyoderma gangrenosum]. PMID- 3325657 TI - [Immuno-phenotype of hairy cell leukemia in the Japanese]. PMID- 3325660 TI - [Transplantation of T cell-depleted marrow from parents in a case of severe combined immunodeficiency with adenosine deaminase deficiency]. PMID- 3325661 TI - [Progress in the hematologic tests in 30 years: serological examinations]. PMID- 3325662 TI - [Prostatic acid phosphatase measured by amplified enzyme linked immunoassay. Its application to mass screening for prostatic tumor and monitoring the clinical course of prostatic cancer patients]. PMID- 3325664 TI - [A case of amyloidosis with severe intrahepatic cholestasis]. PMID- 3325665 TI - [Mucin-producing pancreatic cancer with unfused main pancreatic duct--a case report]. PMID- 3325663 TI - [Ultrasonographic studies of the gallbladder in acute viral hepatitis--with special reference to the relationship between evolution of jaundice and diameter of the gallbladder lumen]. PMID- 3325667 TI - DNA replication study in a female infant with a karyotype of 45,X/46,X, psu dic(X) (p22::p22) and review of the literature. PMID- 3325666 TI - [Renal handling of beta 2-microglobulin and creatinine among residents in a cadmium-polluted area]. PMID- 3325668 TI - Cell growth-inhibitory action of SAGP, an antitumor glycoprotein from Streptococcus pyogenes (Su strain). AB - An antitumor acidic glycoprotein (SAGP) from Streptococcus pyogenes (Su strain) inhibited the growth of BALB/3T3 cells in culture in a dose-dependent manner (0.03-10.0 micrograms/ml). This effect of SAGP was abolished by washing the cells, suggesting that SAGP weakly binds to the cell membrane. The ability of the cells to form colonies was unaffected by three days exposure to SAGP. Cell cycle analysis by flow cytometry revealed an accumulation of SAGP-treated cells in the S-phase. SAGP (3 micrograms/ml) reduced the incorporation of 3H-thymidine into the cells to approximately half of the control level. These results suggest that SAGP inhibits the growth of target cells by acting on their surface membrane and decreasing the rate of DNA synthesis. PMID- 3325669 TI - Surgical treatment of inflammatory bowel disease--a review of some current opinions and controversies. AB - There are many controversial issues regarding the treatment of patients with inflammatory bowel disease. From this review we have concluded that the longer surgery for Crohn's disease is delayed, the higher the rate is of pre- and postoperative complications. A plea is thus made for relatively early surgical intervention. For Crohn's disease, the general policy today is to perform resections, even if relatively limited ones, rather than to perform by-passes of the macroscopically involved intestine. Indeterminate colitis, as well as self limiting colitis, are differential diagnoses that the surgeon must be aware of, especially when selecting the appropriate operative method. Due to the existent risk of cancer in ulcerative colitis, some authors advocate prophylactic colectomy after 10 to 15 years, but the most current policy seems to be one of close surveillance, with surgery only in the cases of severe dysplasia or if a so called dysplasia associated lesion or mass (DALM) is diagnosed. Coloproctectomy has been the standard procedure for patients with ulcerative colitis, however, good or even excellent results are often seen after ileorectal anastomosis and pelvic pouch operations. Although all patients cannot benefit from the latter operation it is likely that it will become the principal operation for patients with ulcerative colitis. PMID- 3325670 TI - Operation for ascending aortic aneurysm and aortic regurgitation--pathological influence on survival. AB - The author briefly reviews the early operations of treatment of aortic aneurysm and aortic regurgitation leading to his description, in 1968, of the first composite graft replacement of the ascending aorta and aortic valve, with anastomosis of the coronary arteries into the graft. The original operation is described with reference to modifications suggested by a number of authors throughout the last 20 years. Methods of achieving coronary artery continuity by Carrel patch and pull-through by saphenous vein interposition and by synthetic graft techniques are discussed. While any of these methods may be needed in individual cases the preference of the author remains for simplicity. The arguments for and against excision of the aneurysmal sac are considered in relation to the control of haemorrhage. The early and medium term results of operation are good but in comparing results world-wide a lack of uniform diagnostic criteria is apparent. The full clinical Marfan syndrome presents little difficulty but the status of "annuloaortic ectasia", Erdheim's medionecrosis, "cystic medial necrosis" and many other pathological descriptions are not defined: "forme fruste" of Marfan's disease has been used for any of the above. Interpretation of surgical results remains difficult and often impossible in the absence of clear definitions. Recent work on elastic tissue and on the chemistry of collagen together with the hope of identification of the genetic background now offers real hope of clearer understanding. PMID- 3325672 TI - Accuracy of suture techniques of surgeons with different surgical experience. AB - The pinpoint accuracy in the suturing techniques of 35 surgeons was measured by the distance deviated from an expected needle exit. The grip of the needle holder used by the surgeons was their habitual one. Accuracy was tested using two ways of suturing; namely with, and without wavering a needle to aim at an exit after suturing began. Where the surgeons did not waver the needle, accuracy improved both when the surgical experience was greater than one year (p less than 0.05) and again when the experience exceeded 10-15 years (not significant). Difference of the accuracy between individual surgeons disappeared in those surgeons with 15 to 20 years experience. Where the surgeons wavered the needle, improvement was more marked in the former period and less in the latter. Wavering improved the accuracy in each group (p less than 0.01), but with the possible danger of injuring tissue. In conclusion, accuracy was not as precise as most surgeons' confidence believed. A significant improvement was observed with 1-year experience, but the improvement thereafter was poor. Fifteen to 20 years experience was not enough to acquire a suturing technique not necessitating needle wavering in the tissue, still yielding a 1.7 mm deviation in a 2 cm suture stride. It was however enough to eliminate surgeons' individual differences in accuracy. PMID- 3325671 TI - Factors influencing insulin secretion after pancreatoduodenectomy. AB - Preoperative patients with periampullary cancer had a higher mean sigma IRI value than that of normal controls, and also had a delayed pattern of insulin response and a lower insulinogenic index during oral-GTT. sigma IRI levels after pancreatoduodenectomy were similar to those of normal controls when the pancreatic remnants were histologically intact at the time of surgery. Postoperative sigma IRI levels could not be predicted based on the extent of histological fibrosis of the distal pancreas at the time of surgery. Patency of pancreatojejunostomy was obtained with the modified Warren's method in 39 out of 40 patients, and sigma IRI levels were maintained up to 5 years postoperatively. No significant difference was found in sigma IRI levels between pancreatoduodenectomised patients with the conventional Roux-en-Y procedure and those with the inverted Roux-en-Y with jejunal interposition. The mean insulin peak value and sigma IRI level were higher in pancreatoduodenectomised patients than in normal controls, and higher in gastrectomised patients than in pancreatoduodenectomised patients. Pancreatoduodenectomy with superior mesenteric arterial dissection resulted in remarkably low sigma IRI levels. PMID- 3325674 TI - A surgically recovered case of spontaneous rupture of the esophagus--the significance of preoperative esophagoscopy for direct suture. AB - A 65-year-old man with spontaneous rupture of the esophagus survived with a direct suture of the esophagus 15 hours after the onset of symptoms. Endoscopic examination of the esophagus was especially of great help in determining the surgical procedure in this patient, and we want to stress the importance of prompt diagnosis and immediate surgery for this disease. PMID- 3325673 TI - A stomach oncofetal antigen recognized by monoclonal antibody GC302. AB - A monoclonal antibody, GC302, was established by fusing murine myeloma NS/1 cells with the splenocytes of a BALB/c mouse immunized with a human gastric cancer cell line, NU-GC-3. The serological specificity of GC302 was analyzed by an anti-mouse Ig mixed-hemadsorption (MHA) test on a panel of human cell lines, and an immunoperoxidase method using the frozen sections of tumors and normal tissues of adult and fetus. GC302 reacted with cancers of the stomach and colorectum but did not react with hepatocellular carcinomas, melanomas, or astrocytomas in the MHA tests. By the immunoperoxidase method, GC302 was found not to react with normal adult gastric mucosa, but to react with the mucosa in the fetal stomach, intestinal metaplasia, and almost all of the cancer of the stomach. GC302 also reacted with the normal mucosa of the intestine, colon, and rectum as well as with cancers of these origins. In normal liver sections, the antibody reacted with the bile ducts, but not with the hepatic cells. These results indicate that the antigen detected by GC302 is characterized as an oncofetal antigen in the stomach, and also as a differentiation antigen whose localization discriminates between the gastrointestinal tracts of the forgut origin and those of the midgut and hindgut origin. The molecular weight of the GC302 antigen was estimated to be ca. 40,000 by the Western blot analysis. Periodic acid treatment on the antigen suggested that the antigenic determinant is a carbohydrate. PMID- 3325675 TI - [A case of myocardial bridging successfully treated by supra-arterial myotomy using CUSA (Cavitron ultrasonic surgical aspirator)]. PMID- 3325676 TI - [Studies on renal damage in percutaneous nephroureterolithotomy. Part 1: A functional study]. PMID- 3325677 TI - [Combined cisplatin and radiation therapy in patients with invasive bladder cancer]. PMID- 3325678 TI - [A clinical and statistical study of 333 cases of renal cell carcinoma. III. Operations, operative findings and results]. PMID- 3325679 TI - [Selective renal biopsy for renal tumor]. PMID- 3325680 TI - Biology of progression of chronic renal diseases. PMID- 3325681 TI - Modulation of brain acetylcholine levels with cholinesterase inhibitors as a treatment of Alzheimer disease. PMID- 3325682 TI - [Decreased lipid levels in arteriosclerotic plaques of the human aorta after LDL apheresis (an in vitro study)]. AB - A comparative study of the effects of LDLP-apheresis on lipids in short-lived organ culture and primary cell culture of human atherosclerotic aorta demonstrated that a fall in free cholesterol, triglycerides, phospholipids and cholesterol esters was largely due to reduced concentration of extracellular lipids. PMID- 3325683 TI - [Electric atrial stimulation in the diagnosis of ischemic heart disease]. PMID- 3325685 TI - [Lasers in cardiology surgery]. PMID- 3325684 TI - [Calcium-regulating hormones and the cardiovascular system: pathophysiological and clinical aspects of their interaction]. PMID- 3325686 TI - [20-year experience with continuous endocardial stimulation of the heart]. AB - Twenty years' experience with continuous endocardial stimulation of the heart is summed up. The bulk of the reviewed data falls to the period of 1980 through 1985, when 1776 primary implantations were performed, whereas more than 3,000 implantations have been performed in the past 6 years. Opinions are voiced on many aspects related to endocardial stimulation. Endocardial application of electrodes is believed to be the principal method, while myocardial stimulation should only be done simultaneously with heart surgery. Electrode application via puncture is discussed with special reference to its advantages (possible application of two electrodes at once, small cosmetic defect) and possible side effects. The results obtained with a borer electrode, designed by the authors, are reported (130 cases). Complications associated with developing rhythm competition are discussed. It is proposed that the manufacture of asynchronous pacemakers be limited considerably, and that they should mostly be implanted in cases of clinically manifest myopotential inhibition. PMID- 3325687 TI - [70th anniversary of Soviet public health and its main objectives]. PMID- 3325688 TI - [Pharmacological protection of the liver in the donor's body for its preservation and transplantation]. PMID- 3325689 TI - [Immunotherapy of bladder carcinoma]. PMID- 3325690 TI - [Preoperative preparation of the large intestine and rectum for planned surgical interventions]. PMID- 3325691 TI - [Diagnostic puncture in abdominal fluid collections]. PMID- 3325692 TI - [Combined surgical method for preventing suppuration of the skin wound after abdominal operations]. PMID- 3325693 TI - [Advantages of the vertical pi-shaped suture of the skin with gauze rolls over the single interrupted suture in abdominal operations]. PMID- 3325694 TI - [Unexplained edema in females--diuretic-induced or idiopathic?]. AB - Both women with diuretic induced edema and with idiopathic edema present a typical history leading to the diagnosis in most cases. These women are almost exclusively in the reproductive age and they tend to have some other characteristics in common additionally. There is controversy whether idiopathic edema exists as a syndrome with multifactorial pathogenesis or if fluid retention in these women is due to diuretic abuse. In either case the use of diuretics is not indicated as they can increase and perpetuate the edema and moreover may bring about impairment of renal function. Abstinence of diuretic intake is the only way out of the vicious circle of fluid retention induced by intermittent diuretic intake resulting in intermittent edema and prostrained use of diuretics. Therapy of idiopathic edema is difficult; it includes physical therapy, psychotherapy and pharmacotherapy with aldosterone antagonists or ACE-inhibitors in some severe cases. PMID- 3325695 TI - [Anti-infectious plant therapies of the forest and savanna regions of Senegal (western Africa). I. A listing]. AB - The use of medicinal plants for the treatment of infectious diseases, by the Diola-boulouf in the Basse Casamance, the South of Senegal, has been studied. The preparation and the indications of 50 plants are described. These data are supplemented with previous reports on the anti-infectious use of these plants. PMID- 3325696 TI - Antimicrobial activity of selected plants employed in the Spanish Mediterranean area. AB - Eighty-one plants from the Spanish Mediterranean area employed as antimicrobial agents in folk medicine have been identified. The in vitro antimicrobial activity of chloroform and methanol extracts of the plants were studied using the agar dilution method against six selected microorganisms. Thirty extracts had activity against some of the microorganisms tested. Bioautography showed that the antimicrobial activity is probably due to flavonoids, terpenoids and phenolic acids. PMID- 3325697 TI - Retinal wholemounts: a simple method for precise mapping. AB - A simple and inexpensive method to analyse retinal wholemounts is described. It allows the definition of regularly spaced sites to map regional specializations of the retina under light microscopy. After attaching a piece of translucent millimetre graph paper behind the slide holding the preparation, the two grid patterns of the graph paper and of the eye-piece grid are used in combination for the definition of sites for analysis and the return to specific areas as small as 50-100 microns2. The present method is simpler and offers several advantages when compared to others based on X-Y movements of the microscope stage or on photographic montage. PMID- 3325698 TI - Calcium entry blocking drugs: their classification and sites of action in smooth muscle cells. AB - This article reviews some of the current thinking regarding the classification of calcium antagonists and explores some of their postulated sites of action in smooth muscle. The relative importance of each reported site of action is discussed. PMID- 3325699 TI - Regulatory functions of adenosine. AB - Adenosine has emerged as an important regulator of many physiological processes. This review briefly describes the formation and inactivation of the nucleoside, its effects in different tissues and the mechanism by which these effects are executed. PMID- 3325700 TI - Morphogenetic effects of glucose on mouse islet-cell re-aggregation in culture. AB - The re-aggregation of dispersed islet cells from non-inbred ob/ob-mice was studied by light and electron microscopy. After 3 days of culture, spontaneously formed aggregates with more than 95% beta-cells were up to 0.5 mm in diameter and exhibited a high degree of viability on dye exclusion tests. In comparison with cultures at 1 or 3 mM D-glucose, or 1 mM D-glucose in combination with 19 mM 3-0 methyl-D-glucose, aggregates formed in 20 mM D-glucose were more closely packed, had a smoother circumference with elongated peripheral beta-cells, and exhibited well developed micro-villi in localized intercellular widenings. A stereological analysis of electron micrographs showed that beta-cells aggregated at 20 mM D glucose exhibited the same individual profile area but a significantly lower form factor, and a significant reduction in granule volume density as compared with aggregates at 3 mM D-glucose. It is concluded that D-glucose has morphogenetic effects on both the cellular and the micro-anatomical level of pseudo-islet structure in culture. PMID- 3325701 TI - [Contact dermatitis caused by nickel]. AB - This paper attempts to explain the initial onset in which the population are sensitized to nickel at an early age, above all in females. A study has been made on 200 controls who tolerated metals and on 964 patents who did not tolerate them. The study comprised of patch tests with 8 distinct washers, made of a variety of metals and alloys all containing nickel, and with nickel sulphate to 1% in petrolatum and cobalt salts to 1% in petrolatum. The results, professional and atopic relationship and other considerations are commented. PMID- 3325702 TI - [Localized cutaneous infantile myofibromatosis. Apropos of a congenital self limiting case]. AB - A case of a 8 year girl presenting a congenital tumoral lesion of the lumbar region is reported. Histologically a hamartomatous fibromatosis was found. A review of the literature was made. The final diagnosis was solitary infantile myofibromatosis, cutaneous type (peculiar form of congenital generalized fibromatosis, also named infantile myofibromatosis). Probably this variety is less rare than thought, because biopsies of apparently benign superficial lesions on children are not usually performed. PMID- 3325703 TI - [Contact dermatitis caused by perfumes and essences contained in various preparations for topical use]. AB - Regarding two cases of allergic contact dermatitis caused by geraniol, containing in two different pharmaceutical products, a revision has been made of the preparations of topical application which contain this and other fragrances. At the same time the clinical picture and examination of these cause is reported. PMID- 3325704 TI - [Chronic disseminated histoplasmosis as an opportunistic infection]. AB - Sixty four patients suffering a chronic disseminated histoplasmosis were studied with the aim of fingind if they had predisposing factors. Thirty cases (46.8%) presented the following predisposing conditions: long treatment with low doses of corticosteroids in 7, ethilic hepatopathy in 7, diabetes in 4, lymphoma in 3, epitheliomas in 3, epitheliomas and diabetes in 1, renal insufficiency in 1, toxic hepatitis in 1, radiations in 1, long treatment with psychotropics in 1 and primary combined immunodeficiency in 1. Only slight differences were detected between these two groups of patients; those who exhibited predisposing factors presented an increased number of clinical localizations, altered cell mediated immunological tests were more frequent as well as the number of patients with multiple relapses and deaths. Histoplasmosis was not the cause of death in any case. It is possible that if a more frequent aggressive exploration, as hepatic biopsy, would be done a higher number of patients with predisposing factors would have been demonstrated. PMID- 3325705 TI - [Painful palmoplantar nodules as the initial manifestation of sarcoidosis]. AB - A 23 year-old woman with sarcoidosis initiated her illness with painful nodules located in palms and soles. This is un unusual clinical finding. Sarcoidosis must be included in the differential diagnosis of painful palmoplantar nodules. PMID- 3325706 TI - [Behcet's disease and pregnancy]. AB - A patient 34 years old, who was diagnosed of Behcet's disease during the third quarter of her pregnancy, is presented here. She was admitted to hospital because a large painful genital ulcer. The treatment with low doses of systemic steroids and steroid ointments allowed us the disease control and the fetal maturing. The fetus was removed by caesarean operation in the 39 week of pregnancy, without complications. PMID- 3325707 TI - [Tuberculous ulcer of the palate. Apropos of a case]. AB - We present a case of orificial tuberculosis in a male of 51, consisting on an ulcer in the pallatum. This diagnosis lead us into finding an advanced active pulmonary tuberculosis which the patient ignored. We want also to emphasize the importance of a correct differential diagnosis regarding oral cavity ulcers, among which we must always keep in mind that tuberculosis is still quite common in our environment, as well as squamous cell carcinoma, reticulum cell sarcoma, eosinophilic granuloma, stomatitis ulceromembranous. PMID- 3325708 TI - [Chromomycosis]. AB - A case of chromomycosis with an evolution of 25 years, in a caucasoid man, aged 57, living in Mozambique, is reported. Fonsecae pedrosoi, the most frequently responsible agent of chromomycosis in Mozambique's cases, was isolated. Prognosis seemed poor since good results from therapy were unexpected, considering the long course of disease, the extensive and fibrotic lesions, and the unsuccessful treatment with 5-fluorocytosine and ketoconazole. The patient was treated with associated amphotericin B-5-fluorocytosine, and topical heat. Clinical improvement and mycologic negative studies were obtained. PMID- 3325709 TI - [Augmentation of the phagocytic activity of monocytes in patients with Darier's disease by the oral administration of retinoic acid]. AB - Other tissue involvement has been described in Darier's disease, eg: susceptibility to infection. In order to know if this susceptibility is due to abnormal phagocytosis and if this can revert by administration of retinoic acid (RA), blood monocyte-derived macrophages, from four individuals with Darier's disease were obtained prior and after administration of RA to determine in them morphological, cytochemical and phagocytic activity changes. It was observed that phagocytosis was diminished and RA administration increased it, without changes in enzyme distribution. This modification of phagocytosis could be due to a reordenation of cytoskeleton. PMID- 3325710 TI - [Candida folliculitis in heroin addicts. Histological study]. AB - Results of histopathologic study of five parenteral heroin users with candida folliculitis are exposed. Candida was found in four, pseudohyphae were observed within the hair, on the keratin of the infundibulum, within the abscess surrounding the hair follicle and horny layer. Blastospores were observed into one arteriole of the dermis. PMID- 3325711 TI - [Behavior of delayed-type hypersensitivity in parapsoriasis]. AB - The authors present a study of behaviour of the late hypersensitivity in fourteen patients carrying parapsoriasis with age varying from 36 to 64 years being nine men and five women with time of the illness development from one to eleven years. There were thirteen white sick people and a yellow one. The parapsoriasis diagnosis was confirmed in all of them clinica and histopathologica. The patients were not getting any therapeutic with corticosteroids or immunosuppressive drugs at the time of study. They were studied immunological through methods in vivo. 1. Methods in vivo. a) Intradermoreactions with the infectious antigens: PPD, trichophytin, levedurin, E. coli. It was used as a control group of fourty normal fellows. b) Sensibility to DNCB. The results obtained allow the following thesis: 1. Low table of positivity to the intradermal reactions to the late reading only one of the antigens tested on the patients (E. coli) related to the others. According to these elements we cannot get at a conclusion for depression of the inespecific cellular immunity in our sick patients. 2. Significant statistics difference on the sensibility test to DNCB on the sick patients related to the controls, a fact which shows a certain degree of the depression of the inespecific cellular immunity. 3. The sick patients with parapsoriasis before taking some treatment should go through the study of a late hypersensitivity. PMID- 3325712 TI - [Hodgkin's disease of the skin]. AB - The authors study a case of Hodgkin's disease type Rye III with specific infiltration of the skin. In cutaneous biopsy we find Reed-Stenberg cells. With treatment the cutaneous lesion diminishes without disappearing. A discussion is made about the Hodgkin's disease and its relation with lymphomatoid papulosis and its differential diagnostic with cutaneous lymphomas and the pathogenic way of cutaneous infiltration. PMID- 3325713 TI - Immunomodulation by oxazaphosphorines. Proceedings of the Oxazaphosphorine Workshop. Bielefeld, June 6, 1986. Dedicated to Prof. Norbert Brock on the occasion of his 75th birthday on May 26, 1987). PMID- 3325714 TI - The MOPC-315 tumor as a model for the immunomodulatory effects of cyclophosphamide. PMID- 3325715 TI - Aspects of the experimental immunopharmacology of oxazaphosphorines. PMID- 3325716 TI - Enhancement of the delayed-type hypersensitivity reaction by oxazaphosphorines. AB - Delayed hypersensitivity reactions include tuberculin type, Jones Mote type reactions and contact sensitivity. These reactions are increased in guinea pigs and other species by pretreating the animals with a single dose of up to 300 mg/kg cyclophosphamide (CY). CY also reverses immunological tolerance and other forms of immunological unresponsiveness, including antigenic competition. Regulation of these hypersensitivity responses may be controlled by CY-sensitive B- or T-suppressor cells, depending on the species and the model. CY does not appear to act by increasing IL-2 production in the same way as other anti-cancer agents. PMID- 3325717 TI - Immunotherapeutic effects of local chemotherapy with an active metabolite of cyclophosphamide. AB - A new approach is described for the use of cytostatic drugs as biological response modifiers (BRM's). Under restricted conditions, strong potentiation of T effector function can be obtained through preferential elimination of suppressor cells. Recent studies from our group have demonstrated that such conditions are fulfilled when low dosages of certain drugs are injected at a site of low antigenic stimulation. Furthermore, local injection of cytostatic drugs not only enhances the development of cell-mediated immunity in non-sensitized animals, but also facilitates the reversal of existing immunological tolerance. These data shed new light on the tumor regression and induction of tumor immunity observed upon intralesional chemotherapy in experimental tumor models. PMID- 3325718 TI - Influence of aldehyde dehydrogenase activity on the sensitivity of lymphocytes and other blood cells to oxazaphosphorines. PMID- 3325719 TI - Preclinical and early clinical trial with mafosfamide as immune modulator. AB - Low doses of cyclophosphamide (CPA) modulate immune responses and induce complete tumor regression and cures in mice. The mechanism of action is related to the development of a T-cell-dependent immune reaction. We started a trial with mafosfamide (MAF), the active metabolite of CPA and found that the response of Ehrlich ascites-tumor (EAT) cells in vivo to this compound is biphasic. The highest cure rate (70%) is obtained with a low i.p. dose of 7 mg/kg/d. Hematologic side effects were not observed. Arguments for an immune mechanism involved are that (1) mice treated with MAF showed a statistically significant increase in spleen weight compared with untreated controls, (2) after treatment large numbers of mononuclear cells appeared in the ascites, and (3) long-term surviving mice were resistant to further challenge with large inocula of EAT. We started a pilot trial in patients with metastasizing and advanced renal cell carcinoma - a disease which can be considered to be influenced by the immunologic response of the tumor host. The starting dose of MAF was 24 mg/m2/d administered i.v. Therapy was repeated at 14 days interval on an out-patient basis. Monitoring of mononuclear cells in the peripheral blood with monoclonal antibodies using a FACS IV were performed two times a week. There are eleven patients on study. Up to now, four out of them have been fully evaluated with respect to toxicity, immune modulation and tumor response. With respect to response to treatment, 2 patients had no change of disease, 1 patient had a mixed and 1 patient a partial response. No hematological or other toxicities could be observed. All patients showed an increase in monocytes/macrophages as well as NK-cells--clearly related to therapy. PMID- 3325720 TI - [Manual suture or stapler technic in anastomoses of the esophago-intestinal tract?]. PMID- 3325722 TI - [Intestinal microflora and the methods of detecting dysbacteriosis]. PMID- 3325721 TI - [Controlled study comparing mechanical and manual esophago-jejunostomy following gastrectomy]. AB - 40 patients with gastric malignancies were entered into a prospective randomised study of mechanical stapling (EEA) vs. manual single layer suturing of the esophago-jejunostomy following total gastrectomy. The groups were well matched with respect to clinical features, medical risk factors and tumor stage. Following manual technique, no anastomotic leak was observed. In the group with automatic mechanical suturing one technical failure and one insufficiency was seen. This difference, however, is not statistically significant. One patient died (cardiac infarction). The analysis of operating time, morbidity and hospital stay showed no significant differences. These results indicate that by use of a precise standardized conventional suture technique the same security performing an esophago-jejunostomy can be achieved as with mechanical staplers. PMID- 3325723 TI - [Ultrasonic diagnosis of liver diseases]. PMID- 3325724 TI - [Veterans of war and work. A survey of materials submitted to Meditsinskaia Sestra]. PMID- 3325725 TI - In situ hybridization and the detection of biotinylated DNA probes. PMID- 3325726 TI - Sequence variation in S-antigen genes of Plasmodium falciparum. AB - S-antigens are soluble heat-stable antigens released into the circulation at the time of schizogony of Plasmodium falciparum. Many serologically distinct S antigens exist and we have shown that this diversity results from repetitive sequences that vary in repeat number, length, sequence and/or reading frame among different S-antigens. We present here the complete sequence of the S-antigen of a Vietnamese isolate V1. The major repeat of 33 base-pairs can be considered to be derived by a deletion event from a 45 base-pair sequence that is located at the 3' repeat boundary and is related in sequence to all S-antigen repeats known so far. We also show that the non-repetitive coding region of the S-antigen gene of V1 is identical to that of K1 and only two amino acids different to that of NF7. In contrast, the sequences are considerably different to those of the FC27 and Wellcome isolates. We conclude that S-antigen genes are highly polymorphic in the repetitive regions but show more restricted diversity in non-repetitive regions. PMID- 3325727 TI - 1987, what happened in Washington. PMID- 3325728 TI - Depressive symptoms displayed by persons with mental retardation: a review. PMID- 3325729 TI - The effect of Michler's ketone on cell division, chromosome number and structure in cultured Chinese hamster cells. AB - The industrial chemical Michler's ketone (MK) has been examined for its ability to induce abnormalities of mitotic cell division and the production of chromosomal aberrations and aneuploidy. MK was shown to produce aberrant cell division stages in cultured mammalian cells probably by interference with centrosome replication leading to the production of monopolar spindles during metaphase, and multipolar telophase spindles, in the first division after exposure. Cells in the second division after exposure to MK showed increased levels of chromosome aneuploidy which is presumed to result from aberrant cell division. There was also some evidence of increased levels of chromosome structural aberrations at concentrations of 1.5 microgram/ml. PMID- 3325730 TI - Disomic and diploid meiotic products induced in Saccharomyces cerevisiae by the salts of 27 elements. AB - The effects of salts of 27 elements on recombination and on the production of disomic and/or diploid spores during meiosis of Saccharomyces cerevisiae has been investigated. Be(NO3)2, MgSO4, FeSO4, CuSO4, AgNO3, Na2HAsO4 were inactive on the events studied during meiotic cell division. AuCl4, CdCl2, C4H6O4Pb, SnCl2, K2Cr2O7, RbCl induced both disomic and diploid spores. LiCl acted similarly and also affected recombination. Activity in the induction of disomic spores was shown by MnSO4, HgCl2 and SrCl2. CsCl, CaCl2, Na2MoO4, NiCl2, K2PtCl4 increased the frequency of diploid spores, while NaWO4, VOSO4, KCl, BaCl2 already increased recombination frequency. NaBiO3 showed an effect on meiotic recombination only. A decrease in the occurrence of both diploid and disomic spores was suggested by the data obtained with CoCl2. PMID- 3325731 TI - cdc7 alleles and the control of induced mutagenesis in yeast. AB - Four cdc7 alleles have been tested for their effects on the u.v.-induced reversion of arg4-17, a highly u.v.-revertible ochre mutant. The extent to which mutability is suppressed parallels the temperature sensitivity of growth of the mutants. The implication is that the pleiotropic consequences of the cdc7 mutations are different manifestations of a single function activity. PMID- 3325732 TI - The prospects for a simplified and internationally harmonized approach to the detection of possible human carcinogens and mutagens. AB - It is proposed that the many sets of Regulatory Guidelines for the assessment of chemical carcinogenicity and mutagenicity should be simplified and harmonized in light of current experimental data. Data are discussed which illustrate that an absolute distinction would be drawn between assays conducted in vitro from those in vivo, and that the genotoxicity of a chemical can be adequately defined using a combination of the Salmonella mutation assay and one for the assessment of chromosome aberrations in vitro. It is specifically recommended that once a chemical has shown a clear positive response in vitro, further short-term assays should be conducted in vivo; this avoids considering the 'weight of evidence' of in vitro data, the dangers of which are illustrated. It has now been unequivocally established that not all in vitro genotoxins prove carcinogenic to mammals. It is therefore recommended that all new in vitro genotoxins should be assessed in vivo using the mouse bone marrow micronucleus assay, and if a negative response is observed, a liver genotoxicity test. At present an assay for the induction of unscheduled DNA synthesis (UDS) in the liver is the most well developed for this purpose. Current data indicate that an in vitro genotoxin found to be inactive in these two in vivo assays will be neither carcinogenic nor mutagenic to the germ cells of mammals. Equally, genotoxicity produced in mammals indicates a carcinogenic and mutagenic potential which can usually only be countered by appropriate chronic bioassays. The use of short-term in vivo assays in this critical role requires attention to the selection of appropriate dose levels and routes of exposure - these issues are discussed. The above testing strategy will not detect certain animal carcinogens, some of which are specifically discussed. These carcinogens have been variously referred to in the literature as epigenetic/non-genotoxic/hormonal/toxic/ambiguous or ambivalent carcinogens. It is suggested that they present a minor potential hazard to man when compared with that of genotoxic carcinogens and that their short-term detection can only be achieved by the development of new whole mammal assays employing non-genetic endpoints. This is in contrast to the present tendency to employ additional genotoxicity assays for their detection in the unjustified belief that they possess an exquisite specificity of genotoxic action. This article represents a personal view, but the testing strategy proposed is based to a large extent on the original three-tier approach of Bridges.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325733 TI - In vivo studies in male mice on the mutagenic effects of inorganic arsenic. AB - The ability of sodium meta-arsenite (NaAsO2) to produce genetic damage in vivo has been evaluated in mice by the micronucleus test on bone marrow cells and the dominant lethality and sperm abnormality assays on male germ cells. The dose related linear increase of micronuclei observed in somatic cells together with the negative results obtained in reproductive cells suggest that NaAsO2, under the conditions of the present experiments, displays clastogenic properties in vivo in laboratory animals, but is unable to produce heritable damage. PMID- 3325734 TI - Structure-activity relationships in the mutagenicity of N-substituted derivatives of phenanthrene-9,10-imine. AB - A series of K-region, N-substituted phenanthrene imines were tested for mutagenicity in Salmonella typhimurium TA100. All chemicals were mutagenic in the absence of an exogenous metabolic activation system. The apparent decay times of the mutagenic species in diffusion plates and their alkylating activities were also measured. The unsubstituted phenanthrene-9,10-imine was approximately 70 fold more mutagenic than the corresponding phenanthrene-9,10-oxide. N substitution with electron-releasing groups resulted in chemicals that were more mutagenic than those substituted with electron-withdrawing groups. The mutagenic activity of the latter group of chemicals was comparable with that of phenanthrene-9,10-oxide. Except for N-chlorophenanthrene imine, both alkylation of p-nitrothiophenol and apparent decay times in diffusion plates were inversely correlated with mutagenicity. It is hypothesized that reactivity towards p nitrothiophenol (alkylating activity) and mutagenicity reflect different reactions, in contrast to other chemical mutagens. The results suggest that the high potency of phenanthrene imines as mutagens is possibly due to DNA binding via an aziridinium ion rather than a carbonium ion. PMID- 3325735 TI - Effect of post-treatments with caffeine during G2 on the frequencies of chromosome-type aberrations produced by X-rays in human lymphocytes during G0 and G1. AB - Human lymphocytes were irradiated with X-rays in G0 and G1, grown in the presence of 5-bromodeoxyuridine, and harvested at different times from 48 to 80 h after stimulation. Some cultures were exposed to 2.5-5 mM caffeine during the last 3 h before harvesting. The frequencies of chromosome-type aberrations were scored in first division (M1) metaphases. The post-treatment with caffeine increased the frequencies of mitoses and chromosome-type aberrations in irradiated cultures. The results suggest that cells carrying chromosome-type aberrations are delayed in G2 and that caffeine increases the frequencies of aberrations in dividing cells by removing this G2-block. PMID- 3325736 TI - Further studies on the detection of mutagenic and genotoxic activity in human faeces: aerobic and anaerobic fluctuation tests with S. typhimurium and E. coli, and the SOS Chromotest. AB - The product of six complete bowel movements were collected from one man (consuming a normal western diet) over a period of 5 months. Aqueous faecal extracts were prepared (0.75 g wet wt./ml water) under aerobic and anaerobic conditions. Graded doses were assayed aerobically and anaerobically for mutagenicity in replicate microtitre fluctuation tests employing histidine reversion in Salmonella typhimurium TA100 and tryptophan reversion in Escherichia coli WP2uvrA(pKM101), and in aerobic SOS Chromotests, using E. coli PQ37. The histidine and tryptophan content of each extract was determined by (i) pre-column derivatisation with o-phthaldialdehyde followed by reverse-phase h.p.l.c. and (ii) by aerobic and anaerobic bioassays employing appropriate auxotrophic strains of S. typhimurium and E. coli. All six faecal samples contained enough histidine and tryptophan or their precursors to compromise the interpretation of fluctuation tests. The h.p.l.c. technique, though quantitatively detecting free tryptophan added to faecal extracts, did not account for growth-enhancing effects of faecal extracts detected by bioassay using bacteria with a requirement for tryptophan. However, h.p.l.c. detected histidine more efficiently than bioassays. A combination of reconstruction experiments and bioassays enabled construction of 'growth windows' within which, in fluctuation tests, dose-related increases in numbers of positive wells could be ascribed to mutation rather than to feeding of auxotrophic bacteria. Under aerobic conditions of extraction and assay, five out of six samples were mutagenic to S. typhimurium TA100, and all six were mutagenic to E. coli WP2uvrA(pKM101). None of the samples extracted and assayed anaerobically was mutagenic to S. typhimurium, but all six were positive in E. coli WP2uvrA(pKM101). There was an increase both in faecal histidine and tryptophan and in mutagenicity during the period of collection, the association between faecal tryptophan and faecal mutagenicity being statistically significant. All the samples were negative in the SOS Chromotests. We conclude that this donor regularly excretes faeces which contain at least two classes of water-soluble directly-acting mutagens which are not detected in SOS Chromotest at doses five times those giving positive effects in fluctuation tests. PMID- 3325737 TI - Abstracts of papers presented at the 9th annual meeting of the United Kingdom Environmental Mutagen Society. Portsmouth, Hampshire, UK, 1-3 April 1985. PMID- 3325738 TI - Sequence of centromere separation: a possible role for repetitive DNA. AB - The centromeres of a mitotic cell at the meta-anaphase junction separate in a non random, genetically controlled sequence before anaphase migration ensues. In several, but not all, of the organisms studied so far it appears that the timing of separation of a centromere into two visible units depends upon the quantity of pericentric heterochromatin. A critical analysis of this parameter of cell cycle suggests that the sequence of centromere separation is influenced by repetitive DNA present in the pericentric region. In those cases with qualitatively uniform repetitive DNA in centromeric regions, the chromosomes carrying lesser quantities separate earlier than those with greater amounts. However, the overall pattern of separation may be determined by interactions between both quantitative and qualitative parameters of the repetitive DNA. It has been suggested that repetitive DNA has no transcriptional properties. It is probably only a structural component which acts as a site for the accumulation of protein molecules synthesized by some locus not present in the centromeric region. These proteins accumulate to saturate the centromeric repetitive DNA resulting in a (trilaminar) structure called the kinetochore. The longer the stretch to be saturated, the larger would be the kinetochore-like structure. Once saturated, the centromere splits into two subunits. Premature separation results in a lack of saturation and formation of an 'immature' kinetochore. This may lead to chromosome malsegregation. Thus, indirectly, one property of repetitive DNA in the centromeric region appears to be the maintenance of diploidy. PMID- 3325739 TI - Evaluation of potential mammalian genotoxins using Drosophila: the need for a change in test strategy. AB - Recent developments in the field of genetic toxicology testing, in particular the outcome of several international collaborative studies, necessitate a re appraisal of the potential use of Drosophila assays for mutagen testing. For an evaluation of the test performance of the classical sex-linked recessive lethal (SLRL) assay to detect as mutagens mammalian carcinogens, the parameters sensitivity, specificity and accuracy were compared, using as a database the Gene Tox Report and the results of two international collaborative studies (CSSTT and IPCS). A characteristic of the assay's performance is its low sensitivity (0.33 0.79) and low accuracy (0.50-0.73), when genotoxins other than direct-acting agents and simple promutagens (single-step activation) were included in the analysis. However, the high specificity (0.86-1.0) of the SLRL assay means that in general a positive result has considerable value for prediction of potential genotoxicity in mammals. Experience in the field of carcinogenesis dictates that organ specificity in one species cannot be predicted on the basis of observations in another. It is concluded here that any attempt to use Drosophila assays on the basis of just exposure dose as predictors of effects likely to occur in specific organs in mammals will fail. Examples are provided by the procarcinogens diethylnitrosamine (DEN), vinyl chloride (VC) and hexamethylphosphoramide (HMPA), as well as by the direct-acting mutagens diethylsulphate (DES), N-methyl-N'-nitro N-nitrosoguanidine (MNNG) and hycanthone. This view is that it would be highly desirable to compare the Drosophila results on germ cells with in vivo mammalian germ-line tests on the basis of molecular dosimetry studies as proposed by Lee. This approach then should enable the comparison on an adequate basis of mechanism of mutagenesis in Drosophila and rodents. It is specifically concluded that the potential value of the SLRL and any other Drosophila germ-cell assay should be judged against their capability of predicting mammalian genotoxicity in a broad sense but certainly not in specific organs. In this function, germ-line assays will have to compete with the novel tests measuring somatic mutation/mitotic recombination (SMART) in Drosophila. The values obtained for sensitivity (0.75 0.78) and accuracy (0.83-0.86) for the latter tests were clearly better than those found for the SLRL test, suggesting that SMART assays present a promising new development. However, the final judgement of their probable role as complementary or confirmatory methods of genotoxic activity observed in Salmonella must await the outcome of the evaluation studies in progress in several laboratories. PMID- 3325740 TI - Experimental model for evaluating the effects of genetic and exogenous factors on transplacental mutagenesis. AB - Cyclophosphamide (CP)-induced micronuclei were evaluated in females of two strains of mice (C57BL and CD1), in F1 hybrid females and in fetuses (day 13 of gestation) obtained from different crosses. F1 adult hybrids from a cross between the strain with a high level of induced micronuclei (C57BL) and the strain with a low response (CD1) exhibited micronuclei values closer to the latter. CD1/CD1 fetuses showed a higher susceptibility than C57BL/C57BL ones. Heterozygous fetuses from reciprocal crosses, whatever the maternal genotype, showed the same sensitivity, which is very close to that of C57BL/C57BL fetuses. Phenobarbital (PB) pre-treatment modified the mutagenic response to CP depending on the genotype of the treated animal. These results demonstrate that the response to a pro-mutagen requiring metabolic activation depends to a large extent on the genetic background of the target animals, and that mother-fetus interactions in transplacental mutagenesis seem to depend more on the fetal than on the maternal genotype. PMID- 3325741 TI - Etoposide (VP16) and teniposide (VM26): novel anticancer drugs, strongly mutagenic in mammalian but not prokaryotic test systems. AB - The mutagenic effect of the antineoplastic drugs VP16 (etoposide; 4' demethylepipodophyllotoxin-ethylidene-beta-D-glucopyranoside) and VM26 (teniposide; 4'-demethylepipodophyllotoxin-thenylidene-beta-D-glucopyr ano side) in mammalian and prokaryotic test systems have been compared. Both VP16 and VM26 which interact with mammalian DNA topoisomerase II, are strongly mutagenic in Chinese hamster ovary cells as indicated by the induction of mutations at the hypoxanthine-guanine phosphoribosyl transferase and adenosine kinase loci, and production of DNA strand breaks and sister-chromatid exchanges. Mouse L cells treated with these drugs also show a large dose-dependent (0.05-0.2 microgram/ml for VM26 and 0.5-1.5 micrograms/ml for VP16) increase in the frequency of 6 thioguanine-resistant mutants and extensive fragmentation of cellular DNA. In contrast to the results obtained with mammalian cells, VP16, which was extensively investigated, showed no increase in revertant frequencies in the Salmonella typhimurium strains TA98 and TA100 at concentrations up to greater than 500 micrograms/plate, in either the absence or presence of an exogenous rat liver activation system. However, a very weak mutagenic response to VP16 and VM26 (less than 2-fold increase in revertant frequency) at very high drug concentrations was observed in the strain TA102. VP16 also failed to show any mutagenic response (up to greater than 500 micrograms/ml) in an excision repair proficient Escherichia coli strain 113/143 employing two different forward mutation detection systems [viz. ability to grow in galactose (Gal+) or in presence of 5-methyltryptophan], which are capable of detecting various types of genetic lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325742 TI - Induction of the cytoplasmic 'petite' mutation in pso mutants of Saccharomyces cerevisiae by photoaddition of furocoumarins or by ultraviolet radiation. AB - The induction of the cytoplasmic 'petite' mutation (or rho-) after photoaddition of either 8-methoxypsoralen (8-MOP) or 3-carbethoxypsoralen (3-CPs), after 254 nm u.v. and after 6-N-hydroxyaminopurine treatment was examined in three pso mutants in comparison to wild-type Saccharomyces cerevisiae. In three pso mutants which are defective in the induction of nuclear reverse and forward mutations, the photoaddition of 8-MOP enhanced the induction of rho-. This was true for cells in both exponential and stationary phases of growth. After photoaddition of 3-CPs in both growth phases the frequency of rho- was enhanced in pso3-1 whereas pso1-1 showed the same response as the wild-type. In pso2-1 the frequency of rho- was reduced. After treatment with 254 nm u.v. in the stationary phase of growth, rho- induction was increased in pso1-1 and pso3-1 cells as compared to wild-type cells. However, when treated in the exponential phase of growth all three pso mutants showed reduced rho- frequency. The data indicate that the defect in the repair of furocoumarins plus light-induced lesions controlled by nuclear genes (pso) interferes to various extents with the fate of mitochondrial lesions. The frequency of rho- mutants induced in the pso mutants by an analogue of adenine, 6 N-hydroxyaminopurine, was similar to that observed in the wild-type strain, suggesting that this drug may also act at the mitochondrial level as a direct mutagen in yeast. PMID- 3325743 TI - The activity of MNNG in the mouse bone marrow micronucleus assay. AB - N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) is established herein as reproducibly active in the mouse bone marrow micronucleus assay. Activity was evident in two strains of mice, using suspensions in water or corn oil, and using two routes of exposure (oral gavage and i.p. injection). Activity was greatest when using the i.p. injection route, but a weak positive response was evident following oral gavage dosing of MNNG as an homogenate in corn oil. The latter weak response was statistically significant and was confirmed by both extended assessment of the slides and by re-analysis of selected slides in an independent laboratory. However, only some of the animals responded, as observed by others earlier. It is concluded that several earlier literature reports of the inactivity of this agent in this assay must be due either to the hydrolysis of MNNG prior to dosing, or to inadequate methods of data acquisition. PMID- 3325744 TI - Cytosolic potentiation of the rat hepatic microsome mediated mutagenicity of benzidine. AB - The role of the cytosolic fraction in the S9-mediated metabolic activation of benzidine to mutagens in the Ames test was investigated using hamster and rat hepatic preparations. Rat microsomes alone were poor activators of benzidine compared to hamster microsomes, at least partly explaining the well known superiority of S9 preparations from the latter species in activating this amine. Supplementation of rat microsomal preparations with the cytosolic fraction from hamsters and to a lesser extent from rats enhanced the bioactivation of benzidine. When hamster microsomal preparations were supplemented with rat or hamster cytosolic fractions no significant effect was observed. Cytosolic fractions from either species could not activate benzidine to mutagens in the absence of microsomes. The cytosolic potentiation of the microsome-mediated activation of the amine was not inducible by Aroclor 1254. Similarly, the microsome-mediated activation of benzidine was not enhanced by Aroclor 1254 pre treatment of the rats, when mutagenicity is expressed per nmol of cytochrome P 450. It is concluded that (i) the cytosolic fraction may play an important role in the metabolic activation by S9 preparations of chemical carcinogens such as benzidine, and (ii) the Aroclor-induced isozymes of cytochrome P-450 do not catalyse the N-hydroxylation of benzidine. PMID- 3325745 TI - Detection of mutagenicity in drinking water using a micronucleus test in newt larvae (Pleurodeles waltl). AB - We have previously described a micronucleus test using erythrocytes from larvae of the urodele amphibians Pleurodeles waltl (pleurodele) and Ambystoma mexicanum (axolotl). The test is based on a comparison of the levels of micronucleated erythrocytes in blood smears from larvae reared in water containing a clastogen, with the levels from larvae reared in purified water. Using larvae from the pleurodele, we have employed this test to evaluate mutagenic activity in drinking water. Groups of larvae were reared in tap water, while control groups were reared in tap water which had been filtered over sand and active carbon to remove micropollutants. Seven separate tests carried out between October 1985 and May 1986 all gave positive results of varying degree depending on the time of year. This test is therefore able to detect clastogens in normal drinking water. It could be used for quality control of drinking water during the various stages in the treatment of raw water without any requirement for prior extraction or concentration of micropollutants. PMID- 3325746 TI - Comparison of the dominant lethal effects of acrylonitrile and acrylamide in male Fischer 344 rats. AB - Acrylonitrile (ACN) and acrylamide (AA), structurally similar vinyl monomers, are both animal carcinogens. ACN is weakly mutagenic in bacteria and induces sister chromatid exchange, unscheduled DNA synthesis and cell transformation in cells in culture. AA induces chromosomal aberrations in bone marrow, blood and germ cells in vivo, and dominant lethal mutations in the germ cells of male mice and rats. In the current study, the ability of AA and ACN to induce dominant lethal mutations in the germ cells of male Fischer 344 rats was compared. Three groups of 50 males were gavaged daily for 5 days with ACN (60 mg/kg in normal saline), AA (30 mg/kg in normal saline) or vehicle only; an additional group of 20 males received a single i.p. injection of 0.2 mg/kg triethylenemelamine (TEM) on the afternoon of day 5. Starting 1 day after exposure, each male was bred to one female per week for 4 weeks (TEM-exposed group) or 10 weeks (ACN, AA and control groups). Mating rates were reduced only during week 1 in the TEM-treated group; pregnancy rates were reduced only during week 2 in the AA-exposed group and week 4 in the TEM-treated group. Females were necropsied 13 days after the end of the appropriate mating week and the amount of pre- and post-implantation loss calculated. ACN treatment of male rats induced no increases in either pre- or post-implantation loss in females in any of the 10 weeks post-exposure examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325747 TI - The hepatic conversion of some heterocyclic amines to bacterial mutagens is modified by dietary fat and cholesterol. AB - Groups of Sprague-Dawley rats were fed on diets containing increasing amounts of beef dripping, but having a constant cholesterol content. One group of rats was fed on a diet containing no dripping and no added cholesterol (control). We have studied the ability of individual hepatic S9 preparations to activate the cooked food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4 dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline (MeIQX) to bacterial mutagens using Salmonella typhimurium TA98 as indicator. Hepatic preparations from animals fed on a high cholesterol, low-fat diet were less effective in activating the mutagens than preparations from rats fed on the control diet. It was also observed that the capacity of hepatic preparations to activate these mutagens increased as the amount of dripping in the diet increased. These results suggest that it is the triglyceride rather than the cholesterol content of beef dripping which promotes increased mutagen activation capacity in the liver. PMID- 3325748 TI - Unambiguous synthesis of asymmetrically substituted chlorinated benzidines, and a study of their mutagenicity in the Ames test: potent activity of 3,5,3' trichlorobenzidine. AB - 3,5-Dichlorobenzidine and 3,5,3'-trichlorobenzidine were prepared by the reaction of 2,6-dichloronitrosobenzene with aniline and 2-chloroaniline, respectively, to give the appropriate substituted azobenzene; reduction and rearrangement gave the desired benzidine derivatives. The products were purified and characterized by mass spectrometry and [1H] nuclear magnetic resonance spectroscopy. The mutagenic activities of the chlorinated benzidines were determined, using the Ames tester strain TA98. 3,5,3'-Trichlorobenzidine is the most potent benzidine derivative yet reported. The activities of five chlorinated benzidines are compared, and rules for the effect of substitution on activity are discussed. PMID- 3325749 TI - Alkaline elution of yeast DNA: a simple method of detection of DNA single-strand breaks. AB - A method of analysis has been developed to study the induction and repair of single-strand breaks in yeast DNA by alkaline elution from filters. By this technique sphaeroplasts obtained from yeast cells were lysed on the filters and single-strand DNA fragments selectively eluted by alkaline elution. Three different approaches are proposed: (i) pH step alkaline elution from the filters; (ii) alkaline elution from the filters using one selected level of pH; (iii) alkaline elution from the filter in which fractions were collected directly on Whatman 17 glass filter paper, thus simplifying the procedure. We found that the first method was the most sensitive, while the next two were much simpler but less sensitive. On the other hand, these two methods enabled us to express semiquantitatively the degree of DNA damage and repair. PMID- 3325751 TI - Mutagenicity testing: new National Toxicology Program (NTP) data confirm old data but question old interpretations. PMID- 3325750 TI - On the mechanism of mitotic segregation induction in Aspergillus nidulans by benzene hydroxy metabolites. AB - The principal hydroxy-metabolites of benzene--hydroquinone, catechol and phenol- were assayed in tests for mitotic segregation induction in Aspergillus nidulans diploid strain 19. Hydroquinone was the most effective chemical, increasing the frequency of mitotic segregants up to 10-fold at 1-3 mM. Catechol was similarly active at 10-20 mM and phenol was weakly positive at 15 mM. Genetic characterization of induced abnormal segregating colonies by replating and complementary assays with haploid strain 35 suggest that gross chromosomal aberrations, instead of numerical abnormalities, are the primary genetic damages induced by hydroxybenzenes in A. nidulans. The protecting activity exerted by L cysteine against equimolar concentrations of hydroquinone supports a free radical mechanism for hydroxybenzenes genotoxicity in A. nidulans. PMID- 3325752 TI - The clastogenicity of chemicals in cultured mammalian cells. PMID- 3325753 TI - The use of in vivo-like concentrations of chemicals for validation of in vitro short-term genotoxicity assays--an in vivo equivalent dose concept. PMID- 3325754 TI - Anaerobic incubation and mutagenicity of nitracrine analogues in Salmonella typhimurium. AB - Nitracrine [1-nitro-9-(dimethylaminopropylamino)-acridine] is a clinical antitumour agent with hypoxia-selective cytotoxicity and radiosensitizing activity. Developments in tumour therapy using either nitracrine itself or some of its analogues under development are likely to be targeted at anaerobic regions of tumours. We have investigated the effects of anaerobiosis on mutagenic activity of nitracrine and a small series of analogues in three derivatives of Salmonella typhimurium frameshift strain hisC3076. Nitracrine-induced mutagenicity was apparently enhanced by a period of anaerobic incubation followed by an aerobic period, with maximal mutagenic effectiveness (as revertants/nmol) being seen at 24 h anaerobiosis. However, the maximal number of nitracrine induced revertants was not increased by anaerobic incubation, and the relationship between mutagenicity and toxicity remained similar. Comparisons of the effects of anaerobiosis on mutagenicity of bacterial strains with different DNA repair capacities suggested that anaerobiosis was not simply depressing 'SOS' repair. Comparisons of nitracrine with four of its analogues showed that this effect was not a universal characteristic of either acridine derivatives or of nitracrine analogues. Rather, the dose displacements obtained paralleled hypoxic cell selective cytotoxicity in mammalian cells. If this result extends to other compounds, experiments of this nature using the bacterial strains could provide a novel and useful screening system to identify hypoxia-selective cytotoxic anticancer drugs of potential clinical value. PMID- 3325755 TI - Mutagenicity of extracts of brown and black masheri, pyrolysed products of tobacco using short-term tests. AB - Black and brown varieties of masheri, which are pyrolysed tobacco products were analysed for their mutagenic potentials using a battery of test systems. Both materials were found to be mutagenic in Salmonella typhimurium strain TA98 with metabolic activation and also in V79 Chinese Hamster cells producing 8-azaguanine resistant mutations. Both varieties were found to induce statistically significant increases in micronuclei formation as compared to those produced in the solvent controls. Both varieties induced structural chromosomal aberrations in bone marrow cells of mice. Our data suggest that masheri is a potent mutagen in a variety of test systems and is likely to have a mutagenic potential vis a vis humans. PMID- 3325757 TI - Mutagenic compounds in an extract from rutae herba (Ruta graveolens L.). I. Mutagenicity is partially caused by furoquinoline alkaloids. AB - Mutagenicity testing of a commercial extract from Rutae Herba (Tinctura Rutae) revealed a strong effect in Salmonella typhimurium strain TA98 without S9 mix. In the presence of S9 mix only a weak response was observed. Moderate mutagenic effects were detected with and without S9 mix using strain TA100. The extract used contained the furoquinoline alkaloids dictamnine, gamma-fagarine, skimmianine, pteleine and kokusaginine, as indicated by g.c. and g.c.-m.s. analysis. The pure compounds exhibited a mutagenic activity only in the presence of S9 mix in strain TA98 as well as in strain TA100, but their specific mutagenicity differed greatly in strain TA98. We conclude that the extract studied contains different mutagenic activities and that these are only partially due to the furoquinolines present in the extract. PMID- 3325756 TI - Benzidine and 3,3'-dichlorobenzidine (DCB) induce micronuclei in the bone marrow and the fetal liver of mice after gavage. AB - Single oral dose of benzidine (300 mg/kg) and DCB (1000 mg/kg) to male ICR mice elicited positive response in the bone marrow micronucleus test. In the transplacental micronucleus test, the compounds were administered to pregnant females in the same manner. A significant increase in the frequency of micronuclei occurred in the fetal liver, but not in the bone marrow of mothers. The relative values of bone marrow and transplacental micronucleus tests for the prediction of carcinogenicity of these compounds is discussed. PMID- 3325758 TI - Methylglyoxal: genotoxicity studies and its effect in vivo on the hepatic microsomal mono-oxygenase system of the mouse. AB - The genotoxic potential of methylglyoxal (MG) was studied in Saccharomyces cerevisiae D7 and in Salmonella typhimurium TA97 and TA102 in the presence and in the absence of metabolic activation system (S9 fraction) prepared from mouse liver induced with beta-naphthoflavone (beta-NF) and sodium phenobarbital (PB). The in vivo effects on the hepatic microsomal mixed function mono-oxygenase system induced by MG were studied in untreated, beta-NF or PB pre-treated mice. MG was a direct-acting mutagen in S. typhimurium TA97 and TA102 when tested up to a maximum concentration of 0.47 mg/plate. Mitotic gene conversion was also induced by MG in the yeast S. cerevisiae D7. A weak but significant effect on reverse point mutation was also found in S. cerevisiae. Genetic activity was lower in the presence of S9 fraction in yeast test. In the in vivo studies, MG (at the total dose of 600 mg/kg) was shown to increase the aminopyrine N demethylase (APD) and p-nitroanisole O-demethylase (p-NAD) activities in uninduced mice. Cytochrome P-450 content (cyt P-450) and ethoxycoumarin O deethylase activity (ECD) were also weakly enhanced by MG treatment. In contrast, no significant changes in mono-oxygenase activities were seen in beta-NF- or PB treated mice after MG injection. PMID- 3325759 TI - Metabolic activation of 3-nitroperylene in the Salmonella/S9 assay. AB - The mutagenicity of 3-nitroperylene (nitroPer), a nitrated polycyclic aromatic hydrocarbon (PAH) has been extensively studied using the Ames Salmonella test. In accord with previous work, nitroPer proved to be a potent frameshift mutagen which requires activation by mixed function oxidases (MFOs) in the microsomes of rat liver S9 preparations. The concentration of S9 required for optimal activation of this mutagen is several times lower than that recommended for routine screening by the Ames test. Studies with the MFO inducers Aroclor 1254, phenobarbital, 3-methylcholanthrene and beta-naphthoflavone, as well as with some MFO inhibitors indicate that both P450b and P450c appear to be involved in the activation of nitroPer. Two non-mutagenic PAHs (perylene and benzo[e]pyrene) inhibited the mutagenicity of nitroPer in a competitive fashion. The mutagenic activity of nitroPer was greatly decreased in a strain of bacteria (TA98/1,8 DNP6) that lacks an acetyltransferase needed for the activation of many nitroarenes. Incubation of nitroPer with microsomes from Aroclor-treated rats plus appropriate cofactors led to the formation of several metabolites which could be separated from one another and from nitroPer by h.p.l.c. Three of these were direct-acting mutagens with Salmonella typhimurium strain TA98, while another required microsomal activation. We postulate that the metabolic activation of nitroPer requires three steps: (i) metabolism by MOF enzymes to yield a ring-oxidized compound which is absorbed by the bacteria; (ii) reduction of this compound to the hydroxylamine by a bacterial nitroreductase; and (iii) O acetylation of the hydroxylamine to yield a reactive ultimate mutagen. PMID- 3325761 TI - An antioxidant protects against the clastogenic effects of benzo[a]-pyrene in the newt in vivo. AB - The clastogenic effect of benzo[a]pyrene (B[a]P) was observed in newt larvae by the formation of micronuclei in circulating red blood cells (RBCs). The level of micronucleated RBCs depended on the concentration of B[a]P (0.025, 0.05 and 0.1 p.p.m.) in the water in which the animals were reared. The synthetic antioxidant, 2(3)-tert-butyl(4) hydroxyanisole (BHA), currently used as a food additive (E 320), was added to the water at concentrations of 0.5, 1.0 and 1.5 p.p.m. It reduced the clastogenic effect of B[a]P in the test larvae, with the most marked effect at a concentration of 0.5 p.p.m. The genotoxicity of B[a]P and the protective action of BHA in the newt are discussed. PMID- 3325760 TI - Synthesis and mutagenicity of selectively methylated analogs of tris(2,3 dibromopropyl)phosphate and 1,2-dibromo-3-chloropropane. AB - Five selectively methylated analogs of the flame retardant tris(2,3 dibromopropyl)phosphate (Tris-BP) and of the nematocide 1,2-dibromo-3 chloropropane (DBCP) were synthesized and their relative mutagenicities determined in Salmonella typhimurium TA100 in the presence of rat liver microsomes. In all cases, methylation decreased mutagenicity relative to the parent compound, but the relative degree of reduced mutagenicity varied considerably depending on the position of the methyl substitution. The mutagenicity studies with the selectively methylated analogs and with suspected mutagenic metabolites (2-bromocrotonaldehyde and methyl 1-dibromovinyl ketone) supported earlier work with selectively deuterated analogs of Tris-BP and DBCP. They demonstrated that initial oxidation at C-3, followed by spontaneous dehydrohalogenation and dehydrophosphorylation, was the major route of formation of mutagenic metabolites from Tris-BP. In the case of DBCP, formation of mutagenic metabolites can result following initial oxidation at either C-1 or C 3. PMID- 3325762 TI - Excision repair and mutagenesis in Saccharomyces cerevisiae. PMID- 3325763 TI - Reply: u.v. mutagenesis in yeast in Escherichia coli. PMID- 3325764 TI - Mutagenicity testing. PMID- 3325765 TI - Post-radiolabelling for detecting DNA damage. PMID- 3325766 TI - Molecular analyses of in vivo hprt mutations in human T-lymphocytes. I. Studies of low frequency 'spontaneous' mutants by Southern blots. AB - Fifty wild-type and 164 in vivo-derived hprt mutant T-cell clones obtained from eight non-mutagen-exposed adult males with mutant frequency values in the normal range (usually less than 10 X 10(-6) were studied by Southern blot analyses to determine frequency and extent of gross structural alterations in the hprt gene. Sixteen (9.8%) of the mutant clones showed hprt changes. No site or type of lesion predominated. Relative frequencies of gross structural alterations in the recovered hprt mutants did not differ among the eight individuals, within limits detectable by the study. DNA from 201 of these 214 clones was also studied with a T-cell receptor (TCR) beta gene probe as a marker for independence of in vivo derived clones. Some clones were also studied with a TCR gamma gene probe. Ninety four percent of wild-type and 89% of the hprt mutants were found to originate from independent in vivo precursors. Therefore, most of the recovered hprt mutants in the study were presumably derived from separate in vivo mutations. For non-mutagenized adults with normal mutant frequencies, in vivo mutant frequencies are thus reasonable approximations of in vivo mutation frequencies, although elsewhere we show that this is not necessarily true for individuals with grossly elevated mutant frequencies. PMID- 3325767 TI - New evidence for the presence of chromosomes in micronuclei of human and Chinese hamster cells. AB - The aim of this work was to demonstrate the presence of intact chromosomes in micronuclei. Such evidence was based on the re-expression of metaphase chromosomes by micronuclei fused with whole cells. Three different experimental approaches were used; they differed only in the criteria used to discriminate between the chromosomes of micronuclear origin and those present in the cell to which micronuclei were fused. These methods involved the expression of: (a) human chromosomes in mouse cells, (b) radioactively labelled human chromosomes in unlabelled human lymphocytes and (c) Chinese hamster chromosomes in Chinese hamster cells with differentially stained chromosomes. With all methods, evidence for the presence of one or few chromosomes in micronuclei was obtained. PMID- 3325768 TI - The effect of 9-beta-D-arabinofuranosyladenine on the formation of X-ray induced chromatid aberrations in X-irradiated G2 human cells. AB - The effects of the nucleoside analogue 9-beta-D-arabinofuranosyladenine (are A) alone or in combination with X-rays on the induction of G2-phase chromosomal damage were studied in immortalized human fibroblasts of lung origin (MRC5-SV1). Ara A is known to be an S-phase specific clastogen, a powerful inhibitor of DNA synthesis and an inhibitor of DNA double-strand break (dsb) repair. The length of the G2-phase of this cell line could be defined as approximately 4 h from data for treatment of cells with ara A alone in which a sharp rise in number of chromatid aberrations was found to occur when ara A treatment times exceeded 4 h; i.e. when cells were in late S-phase at the time of treatment. The frequency of chromatid deletions in X-irradiated G2-phase cells was found to decrease as the time between irradiation and fixation increased. This was interpreted as reflecting the underlying repair of dsb. When X-irradiated cells were treated with ara A between irradiation and fixation, the decrease in deletions found after X-rays alone was not observed. This was interpreted as reflecting the inhibition of dsb repair. Unlike deletions, the yield of exchanges increased during incubation of G2-phase cells after X-ray exposure and the rate of this increase was found to be trebled by the addition of ara A to the medium. We postulate that the increased rate of exchange aberration formation in the absence of dsb repair indicates the existence of a second 'error-prone' misjoining mechanism which is independent of DNA synthesis. PMID- 3325769 TI - The toxicity and mutagenicity of the anti-tumour drug 5-aziridino-2,4 dinitrobenzamide (CB1954) is greatly reduced in a nitroreductase-deficient strain of E. coli. AB - In the 1970s it was shown that the monofunctional alkylating agent CB1954 (5 aziridino-2,4-dinitrobenzamide) kills the Walker rat carcinoma 256 in vivo and in vitro, but is inactive against several other tumours. In studies with bacteria, the large differences in survival in DNA-repair-proficient and deficient strains of Escherichia coli B treated with CB1954 were characteristic of a difunctional cross-linking agent. It was concluded that DNA was the only target large enough to receive significantly more than one lethal hit per molecule and that mono alkylation alone could not account for the lethal effects of CB1954. In 1986 it was shown that CB1954 induced DNA interstrand cross-links in CB1954-sensitive cultured Walker 256 cells, but not in resistant Chinese hamster V79 cells, suggesting that the sensitivity of Walker cells results mainly from their activation of the drug to a difunctional agent by nitroreduction. To test this, we assayed the toxicity and mutagenicity of CB1954 in nitroreductase-plus and minus strains of E. coli WP2uvrA. Agar-overlay assays showed that CB1954 was mutagenic to several strains of E. coli WP2, in a dose range 1-100 micrograms per plate, with slopes (mutants/nmol) of 7.1, 1.05 and 0.16 for WP2uvrA pKM101, WP2uvrA and WP2. Assays with nitrofurazone showed that these strains possessed nitroreductase activity. However, E. coli NFR-343, a nitrofurazone-resistant mutant of WP2uvrA which lacks nitroreductase activity was markedly less sensitive to the mutagenicity of CB1954, giving a mean slope of 0.12 compared with 1.15 for WP2uvrA. Aroclor-induced rat-liver S9 did not change these responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325770 TI - Methods of analysis of data on mitotic aneuploidy. AB - The induction of aneuploidy in cultured mammalian cells has been studied using two chemical agents, diethylstilboestrol dipropionate and Colcemid, which act on the mitotic spindle, in order to investigate different methods of scoring and statistical analysis. Two cell lines, one human and the other Chinese hamster, were each exposed to one test agent, and metaphase preparations scored (a) counting all the chromosomes and (b) counting only the chromosomes of a selected group within the karyotype, to assess which would be the more rapid means of scoring metaphases for aneuploidy. Both the numbers of aneuploid cells and, where appropriate, the total numbers of chromosomes lost and gained were analysed using regression analysis, G-statistics and chi 2 or Fisher's exact test. The results indicate that counting selective chromosomes may in certain circumstances be advantageous, but will result in many more metaphases being required to be scored. Regression analysis to demonstrate dose response is suitable for the analysis of strong positives, but it is suggested that with weak inducers of aneuploidy, the additional tests cited above, using either the number of aneuploid cells or the actual number of chromosomes lost and gained are more sensitive measures of the effects. PMID- 3325772 TI - Mutagenicity testing. PMID- 3325771 TI - Critical features of bacterial mutation assays. AB - This review discusses features of the standard protocols currently used in bacterial mutation assays which can have a critical effect upon the test outcome. Such features if not strictly controlled may affect the results qualitatively as well as quantitatively. These include the dose-intervals of the test compound used; the number of bacterial cells exposed to the test compound; the phase of growth such cells are in during exposure; and the length of time that the cells are exposed prior to the addition of soft agar (in the Salmonella/plate incorporation assay). The following possible modulating effects will also be discussed: the nature of the solvent used; the nature and quantity of the exogenous metabolizing system (usually liver S9-fraction) and the quantity of amino-acid (e.g. histidine) within the test system being that either deliberately added or present unavoidably within the test sample (e.g. biological fluids). If bacterial mutagenicity assays are to realize their full potential for the detection of genotoxic carcinogens, the use of rigid protocols should be discouraged. Where possible, consideration of the compound's structure should lead to the employment of the optimal protocol for the detection of genotoxic carcinogens within that chemical class. The relative speed and low cost of bacterial assays should be exploited in this way to avoid the generation of false negative results during the primary screening of novel compounds. PMID- 3325773 TI - Identification of the domain of Saccharomyces cerevisiae adenylate cyclase associated with the regulatory function of RAS products. AB - Various truncated CYR1 genes of Saccharomyces cerevisiae were fused to efficient promoters and expressed in Escherichia coli and S. cerevisiae cells with or without the RAS genes. The catalytic domain of adenylate cyclase encoded by the 3'-terminal 1.3 kb region of the open reading frame of the CYR1 gene produced cyclic AMP, irrespective of the presence of RAS genes. The product of the 3' terminal 2.1 kb region of CYR1 showed guanine nucleotide-dependent adenylate cyclase activity and produced a large amount of cAMP in the presence of the RAS gene. Thus, the domain encoded by the 0.8 kb region adjacent to the catalytic domain is associated with the regulatory function of the RAS products. The cyr1 RAS1 RAS2 cells carrying the 3'-terminal 1.3 kb region of CYR1 were unable to respond to environmental signals such as sulfur starvation and temperature shift, but the cyr1 cells carrying the 2.1 kb region and at least one RAS gene were able to respond to these signals. The environmental signals may be transferred to the adenylate cyclase system through the RAS products. PMID- 3325774 TI - Isolation and characterization of Escherichia coli birA intragenic suppressors. AB - The biotin (bio) operon in Escherichia coli is negatively regulated by BirA, a bifunctional protein with both repressor and biotin-activating functions. Twenty five heat-resistant revertants of three temperature-sensitive birA alleles (birA85, birA104 and birA879) were isolated and categorized into five growth and six repression classes. The revertants appear to increase biotin activation by raising the specific activity of BirA and/or increasing the number of enzyme molecules. The 19 birA85 revertants displayed a broad range of activity for both enzyme and repressor functions, and may represent intragenic second-site suppressor mutations. The birA85 revertants included a novel class of bio superrepressor mutations. Repressor titration experiments suggested that many of the birA85 revertants increase BirA concentrations above wild-type levels because the repressors were not competed from the chromosomal bio operator by multicopy bio operator plasmids. The majority of the birA104 revertants resulted in both wild-type repressor and enzyme activity; they are possibly true revertants in which the amino acid residue altered by the birA104 mutation has been substituted by the wild-type or a chemically similar amino acid. PMID- 3325775 TI - Expression of the Escherichia coli trpE gene in E. coli K12 bacteria: maximum level, rate and time of initiation of anthranilate synthetase production. AB - We have investigated the effect of alterations in the structure of the plasmid borne Escherichia coli tryptophan (trp) coding region and other regions of the same replicon on the level, rate and time of initiation of anthranilate synthetase component I (ASase) synthesis in E. coli K12. The maximum level of ASase produced corresponds to 60%-65% of the total cellular proteins. Adding sequences downstream of the trpE coding region decreases the level but does not affect the time of initiation and rate of trpE expression (ASase synthesis). The presence of additional protein coding sequences on the plasmid outside the trpE-A region causes ASase production to start earlier and decreases the rate of ASase synthesis. A second copy of the trpE coding sequences, if present within or outside the trpE-A coding region on the same replicon, doubles the rate of synthesis of ASase and slightly increases its final level of production. The initiation of ASase production occurs earlier when the two trpE copies are located within two distinct transcription units. PMID- 3325776 TI - CAN1-SUC2 gene fusion studies in Saccharomyces cerevisiae. AB - Various gene fusions between the arginine permease and invertase have been constructed in order to obtain information about whether parts of the CAN1 gene product can induce secretion of biologically active invertase missing its own signal sequence. A construction containing 30 N-terminal amino acid residues of the CAN1 gene product fused to invertase was not secreted. When the CAN1 portion was elongated to 477 or 560 amino acid residues, secretion of the fusion proteins was observed. A fusion lacking 59 amino acids at the amino-terminal end of the arginine permease was also secreted. These results indicate that the amino terminal end of the arginine permease is neither sufficient nor essential for membrane insertion; instead this enzyme should contain an internal targeting sequence facilitating secretion. Some general implications on the biosynthesis and topology of membrane proteins are also discussed as well as the homology with histidine permease. PMID- 3325777 TI - Transductional analysis of chromosome replication time. AB - Following transduction of exponentially growing cultures of Escherichia coli with phage P1, cells with recombinant phenotype begin to increase in number after an initial lag of about one generation time. We show that transductants for markers located at different positions on the chromosome begin to increase at different times, in reverse order to that in which they are replicated. The period over which this happens is equal in duration to the time taken to replicate the chromosome and we have used this relationship to calculate the C-period of E. coli K12 growing at 30 degrees C. We exclude transduction-induced filamentation as the cause of the initial lag and suggest that the lag may result from the way in which donor DNA is inherited. PMID- 3325778 TI - The Saccharomyces cerevisiae MET3 gene: nucleotide sequence and relationship of the 5' non-coding region to that of MET25. AB - In Saccharomyces cerevisiae, the expression of several genes implicated in methionine biosynthesis is co-regulated by a specific negative control. To elucidate the molecular basis of this regulation, we have cloned two of these genes, MET3 and MET25. The sequence of MET25 has already been determined (Kerjan et al. 1986). Here, we report the nucleotide sequence of the MET3 gene along with its 5' and 3' flanking regions. Plasmids bearing different deletions upstream of the transcribed region of MET3 were constructed. They were introduced into yeast cells and tested for their ability to complement met3 mutations and to respond to regulation by exogenous methionine. The regulatory region was located within a 100 bp region. The sequence of this regulatory region was compared with that of MET25. A short common sequence which occurs 250-280 bp upstream of the translation initiation codon of the gene was found. This sequence is a good candidate for the cis-acting regulatory element. PMID- 3325779 TI - The organization of the fuc regulon specifying L-fucose dissimilation in Escherichia coli K12 as determined by gene cloning. AB - In Escherichia coli the six known genes specifying the utilization of L-fucose as carbon and energy source cluster at 60.2 min and constitute a regulon. These genes include fucP (encoding L-fucose permease), fucI (encoding L-fucose isomerase), fucK (encoding L-fuculose kinase), fucA (encoding L-fuculose 1 phosphate aldolase), fucO (encoding L-1,2-propanediol oxidoreductase), and fucR (encoding the regulatory protein). In this study the fuc genes were cloned and their positions on the chromosome were established by restriction endonuclease and complementation analyses. Clockwise, the gene order is: fucO-fucA-fucP-fucI fucK-fucR. The operons comprising the structural genes and the direction of transcription were determined by complementation analysis and Southern blot hybridization. The fucPIK and fucA operons are transcribed clockwise. The fucO operon is transcribed counterclockwise. The fucR gene product activates the three structural operons in trans. PMID- 3325780 TI - Direct evidence for rifampicin-promoted readthrough of the partial terminator tL7 in the rpoBC operon of Escherichia coli. AB - The RNA polymerase subunits beta and beta' of Escherichia coli, encoded by the genes rpoB and rpoC, are co-transcribed with four 50 S ribosomal protein genes, rplKAJL. After treatment with the antibiotic rifampicin a partial uncoupling of rpoBC from rplKAJL transcription occurs. We have been investigating the role played in uncoupling by tL7, an 80% efficient terminator of transcription present in the 319 bp intercistronic space between rplL and rpoB, using S1 nuclease mapping of transcripts produced in vivo in normal (rpoBC haploid) strains. Our results show directly that rifampicin stimulates readthrough of tL7 on the chromosome by approximately twofold, an effect sufficient to explain the observed increase in beta beta' protein synthesis. We also provide preliminary evidence for the map position of PL7, and show that both this and P beta, two very weak promoters which might in principle be activated by rifampicin, are not in fact stimulated by the drug. PMID- 3325781 TI - Nucleotide sequence of putC, the regulatory region for the put regulon of Escherichia coli K12. AB - The nucleotide sequence of the putC region, from which divergent transcription of the putP and putA genes starts, was determined. The promoter region for the putA gene was restricted to the location between the HindIII site and the NcoI site or at the NcoI site by using putA-lacZ fusion plasmids and the transcriptional start for the putA gene was identified in the region between the HindIII site and the NcoI site by Sl mapping. This region also contains a potential CAP binding site, a ribosome binding site, and a sequence that is highly homologous to argTr. Five potential promoters (putPp1-putPp5) for the putP gene, which were separate from the promoter region for the putA gene, were indicated by S1 mapping analysis of the putP gene transcripts. We concluded that the putC region is 419 bp long and contains two independent sets of promoters, regulating the expression of putP and putA genes in opposite directions. In addition, this region was found to contain an open reading frame (orf) capable of encoding a polypeptide of 111 amino acids in overlapping fashion. But studies using an orf-lacZ fusion gene showed that this open reading frame was not expressed. PMID- 3325783 TI - Fluorometric enzyme-linked immunosorbent assay for the measurement of IgE antibody to mite Dermatophagoides farinae. AB - We have developed a fluorometric enzyme-linked immunosorbent assay for measuring IgE antibody to Dermatophagoides farinae. Polystyrene microplates were coated with proteins extracted from the mites. The IgE antibody which attached to the solid-phase antigen was detected by anti-IgE antibody conjugated with beta galactosidase. Four-methylumbelliferyl-beta-D-galactoside was used as the enzyme substrate and the fluorescence intensity of the reaction product was measured. The antibody levels determined by this method well correlated with those determined by the radioallergosorbent test (RAST). This method is simpler and less expensive to carry out than the RAST when dealing with a large number of serum specimens for seroepidemiological studies of asthma and nasal allergy. PMID- 3325784 TI - [Constipation and laxatives]. PMID- 3325782 TI - Effect of aculeacin A on reverting protoplasts of Candida albicans. AB - Protoplasts of Candida albicans were prepared by digestion with Zymolyase and the effect of aculeacin A, a wall-active antibiotic, on the synthesis of microfibrillar structures by the protoplasts incubated for 5 hr in an osmotically stabilized medium was studied using several electron microscopical techniques. Chemical analyses of the protoplasts before and after reversion with or without the antibiotic were also performed. Aculeacin A not only inhibited synthesis of microfibrils mainly composed of alkali-insoluble beta-glucan, but also their assembly to form thicker bundles. The antibiotic appeared to have no effect on other wall components constituting the surface structure of reverting protoplasts. These data confirmed our previous postulation that aculeacin A is a specific and potent inhibitor of beta-glucan synthesis as well as biogenesis of cell walls including beta-glucans in susceptible yeasts. PMID- 3325785 TI - [Anti-arrhythmia drugs--administration and effectiveness]. PMID- 3325786 TI - [Familial hypercholesterolemia]. PMID- 3325787 TI - [Laboratory model of alveolar hydatid disease of the liver]. PMID- 3325788 TI - [Clinico-immunological aspects of parasite-host relations]. PMID- 3325789 TI - [Case of clonorchiasis undiagnosed during life]. PMID- 3325790 TI - [Economic loss from dysentery combined with ascariasis and trichocephaliasis]. PMID- 3325791 TI - [Biochemical principles of the action of drugs in malaria]. PMID- 3325792 TI - [On the centenary of the birth of Fedor Mikhailovich Toporkov (1887-1950)]. PMID- 3325793 TI - Plasmid incompatibility. PMID- 3325796 TI - [Jarcho-Levin syndrome. Description of a familial case and review of the literature]. PMID- 3325795 TI - Regulation of solute transport in streptococci by external and internal pH values. PMID- 3325794 TI - Bacterial uptake of aminoglycoside antibiotics. PMID- 3325797 TI - [Autologous bone marrow transplantation in Burkitt's lymphoma]. PMID- 3325799 TI - [Intracranial hemorrhage in the newborn infant. Etiopathogenesis and instrumental diagnosis]. PMID- 3325798 TI - [Pretreatment growth rate and response to therapy with growth hormone (HGH)]. PMID- 3325801 TI - Complexity of neurotoxicological assessment. AB - One of the central objections to routine behavioral testing concerns the difficulty in interpreting behavioral effects. This paper discusses the assessment of neurotoxic hazard using data from both conventional toxicity studies and behavioral studies. It describes the breadth and complex expression of neurotoxic effects, the inference of neurotoxicity from behavioral and other data, and the validity and interpretation of behavioral effects. The basic questions asked by regulatory petition reviewers include: (1) can an effect be identified; (2) can the effect be considered to be a function of exposure; (3) can the effect be considered to be a direct effect on the nervous system; and (4) can the effect be considered to be an adverse effect? Approaches and options for improving the interpretability of current testing strategies are described. These include improvements and additions to existing studies, explicit testing, and development of generic testing requirements for specific chemical classes. PMID- 3325800 TI - The use of traditional toxicologic data in assessing neurobehavioral dysfunction. AB - In the United States, the regulation and testing of chemicals that may impact on human health is mandated by a number of different laws and regulated by several government agencies. Toxicologic screening in laboratory animals has created a major database for predicting adverse health effects of drugs, food and cosmetic ingredients, and manufactured chemicals. Test protocols and reporting requirements frequently differ between government agencies within the United States and between nations. Until recently, the emphasis for this required testing has been to identify those chemicals that may result in cancer or birth defects with little or no emphasis placed on neurobehavioral testing. The so called "traditional toxicologic screen" presently includes acute, subchronic, chronic, teratology, and reproductive multispecies testing. The report for each segment of the test screen contains a myriad of data elements that have been observed by numerous technicians in the testing laboratory. These laboratory tests vary from general animal observations of animal body weight and food consumption to tests for hematology, blood chemistry, urinalysis, and histopathology. In addition, specialized tests may include other physiological measurements, neurologic tests, eye exams as well as functional testing to evaluate performance (e.g., open field, swimming maze, and T-maze). Reliability, quality control, and the difficulty in converting technician observation into quantifiable data elements that are free from bias is a primary concern for all testing laboratories. This paper focuses on the neurotoxicologic and behavioral information that can be gleaned from traditional toxicologic screens, the collection of study data, the effect of model selection, and the environmental considerations that may affect study outcome. The paper includes examples of compounds previously reported in the literature. PMID- 3325802 TI - Mechanisms of CNS injury in behavioral dysfunction. AB - Advances in the neurosciences have led to a greater understanding of the anatomical, biochemical, and molecular loci involved in injury to, and adaptation of, the central nervous system. Recent research has permitted the elucidation of the mechanisms for some neurotoxicants whose actions have been studied for decades, as in the example of the pyrethroid insecticides. In contrast, the mechanism of the neurotoxicity of the organophosphate insecticides and nerve gases has been known for many years, but our understanding of the many resulting sequelae has been markedly increased by recent discoveries. Two examples illustrate the strengths and weaknesses of such methods in predicting neurotoxicity. Studies of the parkinsonian-like toxicity caused by 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) (a by-product of synthesis of illicit opiates) exemplify the best application of current methods in neurotoxicology. It has been shown that the expression of MPTP toxicity requires both metabolism of MPTP to the proximal toxicant 1-methyl-4-phenylpyridinium (MPP+) and active uptake into central dopamine neurons. The discovery of binding sites of MPP+ in these cells has clarified how dopamine neurons are destroyed, thereby causing neurological signs. This illustrates two key concepts: first, the bioconversion of compounds to proximal toxicants is often ignored, and second, these events are unlikely to be detectable by in vitro studies that focus on a few biochemical endpoints. Another useful example was that of erythrosin (FD&C Red No. 3), in which numerous in vitro studies suggested that this food color was a potential neurotoxicant. However, this was shown to be an artifact of the ability of this color to disrupt biomembranes at high in vitro concentrations, and this idea was supported by negative data from both behavioral and clinical studies. Thus, the plethora of possible molecular and biochemical targets in the central nervous system (receptors, second messenger events, transmitter-modulator synthesis, storage and release, membrane maintenance, etc.) preclude the likelihood of developing a single test or a battery of neurochemical or biochemical tests that will be able to screen for neurotoxicants randomly or efficiently. Use of in vitro methods is likely to detect both false positives and negatives. While the availability of theoretical or phenomenological data provides the best start to the application of available biochemical and molecular techniques, predictions of neurotoxicity best can come from theoretical comparison of the structure of suspect compounds (and hypothesized metabolites) with known target sites in the CNS.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3325804 TI - Reliability, sensitivity and validity of behavioral indices of neurotoxicity. AB - Adequate sensitivity, reliability, and validity are features of scientific testing in all fields. Accordingly, these have been central concerns in the development of behavioral methods for assessing neurotoxicity. Advances during the last 10 years have established behavioral tests that show high degrees of sensitivity and reliability both within and across laboratories. This was demonstrated in the recently completed National Center for Toxicological Research (NCTR) Collaborative Behavioral Teratology Study and other collaborative studies. Validity of behavioral testing has been based on: (a) the use of known neurotoxins; (b) comparison of agents causing behavioral dysfunction in humans; and (c) theoretical considerations of domain of central nervous system (CNS) function to be evaluated. These approaches have worked well, however, the neurochemical/neuropathologic to behavior correlations have been effective only under circumstances where a neurotoxic compound, as recognized by an identifiable neurobiologic signature, has been available. Behavioral methods are important in neurotoxicity evaluations because they provide an assessment of overall CNS functional integrity, whereas other methods in the neurosciences are directed towards specific subsystems. This presentation discusses the validity of measurements in: (1) behavioral testing; (2) neuropathologic evaluations; (3) neurochemical tests; and (4) electrophysiological techniques for detecting neurotoxicity. PMID- 3325803 TI - Behavioral indices of neurotoxicity: what can be measured? AB - The ability to identify and characterize the potential neurotoxicity of chemicals is an important and necessary function of various regulatory agencies. Behavioral assessments of toxicity may be important because of their relative sensitivity to some chemicals, their generally noninvasive characteristics, and their ability to measure toxicity in organ systems other than the nervous system. Behavioral tests can be classified by several criteria including traditional experimental definitions, their desired experimental usage, the neurobehavioral functions they are designed to assess, and the strategy chosen for their use in the evaluation of chemicals. Examples of neurobehavioral tests used to evaluate the effects of chemicals for toxicity include those that evaluate motor (spontaneous motor activity, motor coordination, weakness, abnormal movement or posture, tremor, and on-going performance), sensory (screening, reflex modification, and instrumental conditioning), learning/memory (nonassociative and associative), instrumental performance (schedules of reinforcement), and naturally occurring responses (consummatory behaviors). Behavioral procedures have also been utilized in select ways in toxicological research to detect latent damage, to study mechanisms of action, and to screen for functional dysfunction following exposure during development. Many considerations, such as the behavioral mechanism of action, definition of an adverse effect, problem of functional reserve, and several statistical questions, should be taken into account in the use and interpretation of data obtained from behavioral tests. During the last decade, there have been numerous recommendations from groups within the United States and, most recently, the World Health Organization, suggesting that systematic observational assessments may be appropriate when carried out within already existing toxicological protocols. PMID- 3325805 TI - Psychoneuroimmunology, new approaches to neurobehavioral testing. AB - A review of the literature in the field of psychoneuroimmunology was reported by Robert Ader [1]. Basically, three research approaches have been used to demonstrate a relationship between central sites within the brain that have modulatory influences on the immune system. These include: (1) both the electrical stimulation and surgical lesioning of nuclei in the hypothalamus; (2) traditional behavioral conditioning; and (3) behavioral stress studies. The mechanisms of action for the psychoneuroimmunologic response appear to be focused in three areas: (1) the autonomic nervous system, where direct anatomical connections from the brain to the immune system have been recently demonstrated; (2) the endocrine system where the individual hormones have direct and indirect effects on the immune system; and (3) enkephalins-endorphins in the brain, pituitary, and adrenals that also have direct and indirect effects on the immune system. Examples of drug effects on the above complex systems will be centered on morphine and the enkephalins-endorphins with reference to drugs of abuse, food additives, and cosmetics. PMID- 3325806 TI - Financing care for the seriously mentally ill. PMID- 3325807 TI - Outpatient commitment for the chronically mentally ill: law and policy. PMID- 3325808 TI - Mental health policy in post-World War II America. PMID- 3325809 TI - Evolution of mental health services and areas for change. PMID- 3325810 TI - Help-seeking processes and mental health services. PMID- 3325811 TI - Services organization and quality of life among the seriously mentally ill. PMID- 3325812 TI - Issues in case management for the chronically mentally ill. PMID- 3325813 TI - Obstacles in urban housing policy for the chronically mentally ill. PMID- 3325814 TI - Substituted judgment and protective intervention. PMID- 3325815 TI - The political context of mental health care. PMID- 3325816 TI - The molecular pathology of IgG4 in allergic conditions. AB - In the time available, I have built up a picture of the molecular pathology of IgE antibodies; and considered that of IgG4 antibodies in comparison. As will have become apparent, much less direct evidence is available on the latter; partly because of lack of reliable and relevant in vitro functional assays. Nevertheless, I hope that in speculating on the possible molecular pathology of IgG4 antibodies, I have said enough to convince you that their likely mode of action in immediate-type hypersensitivity reactions will prove to be fundamentally different to that of IgE antibodies. It is important to bear this in mind in attempts to devise suitable assays of use in clinical diagnosis; and in considering their unique contributions to allergic reactions. PMID- 3325817 TI - A review of in-vitro assays for IgG and IgG4 antibodies: concept and potential applications. AB - In-vitro assays for the diagnosis of allergy presently are quite common, having been demonstrated by a number of investigators to possess a high degree of specificity and sensitivity. These assays are for the most part rapid, flexible, and when utilized properly, cost effective. It has long been known that antibodies, other than the homocytotropic antibodies, are involved in allergy. The concept of "blocking antibodies" was first introduced by Cooke in 1935. He demonstrated that these antibodies could neutralize the effects of reagins present in the sera of allergic individuals. Since that time investigators have developed a series of techniques to assess and define blocking antibodies. These techniques include inhibition of antigen-induced histamine release from peripheral blood leukocytes, hemagglutination with allergen coated erythrocytes, radio-allergo-sorbent test (RAST), define antigen substrate sphere (DASS), antigen binding radioimmuno assay, and more recently, enzyme-linked immunosorbent assays (ELISA). These methods have been utilized to show that "blocking antibodies" are predominantly of the IgG class. Recently, several assays have been introduced to the clinical laboratory for the purpose of monitoring the production of blocking antibodies (i.e., IgG) in response to immunotherapy. These assays, while adding an important tool to the arsenal of the clinical practitioner, may have limited utility because of a lack of specificity and sensitivity. Recently, 3M Diagnostic Systems (3MDS) has introduced an assay via its Reference Laboratory designed for the measurement of what many investigators feel is the appropriate marker for monitoring immunotherapy . . . the IgG4 subclass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325818 TI - IgG subclass antibody markers in grass pollen immunotherapy. AB - Rye grass immunotherapy was clinically effective in seasonal allergic asthma and induced serologic changes different from those of natural exposure. These included the blunting of the seasonal rise in IgE antibody and much greater increases in blocking IgG antibodies. Blocking antibody responses to rye grass antigens were restricted to the IgG1 and IgG4 subclasses. Nonatopic individuals had similar preseasonal levels of IgG1 antibodies, but low or undetectable levels of IgG4 or IgE, compared to allergic subjects. Immunotherapy induced increases in both IgG1 and IgG4 antibodies, but IgG4 was dominant and the rise was much more dramatic. Rye grass extract contained at least eight IgE binding allergens and 11 IgG binding antigens, by far the most important of which was antigen I. IgE and IgG binding antigens generally showed concurrence in individuals, but heterogeneity between individuals for non-Rye 1 antigens. Finally, while IgG4 quantitatively dominated the blocking response, early clinical benefits might involve IgG1 antibodies, suggested by an observed inverse correlation between individual symptom medication scores individuals and IgG1 antibody levels. PMID- 3325819 TI - The development of specific IgG4 after immunotherapy with standardized extracts. AB - A significant reduction in symptoms scores was observed in those patients who elected to continue their immunotherapy after achieving maintenance. All of those patients developed allergen specific IgG4 within a year of post-maintenance injections. These findings suggest that a reduction of allergic symptoms is accompanied by a rise in specific IgG4 antibody against the offending allergen(s). These specific IgG4 antibodies can be induced by appropriate immunotherapy. Lastly, allergen specific IgG4 antibodies were rapidly and accurately determined using the 3M IgG4 FAST test. PMID- 3325820 TI - IgG subclass antibody response to hymenoptera venom. AB - Venom immunotherapy provides clinical protection against hymenoptera stings in almost all treated allergic patients. Venom specific IgG antibodies often rise during immunotherapy and some studies found an association between their levels and clinical protection in subjects treated with Yellow Jacket venom. It is interesting to report that, among IgG subclasses, venom specific IgG4 show the most significant increase but IgG1 could represent a relevant immunological mechanism, exerting a regulatory function on venom specific IgE levels. We observed in patients submitted to Honey Bee venom immunotherapy a significant increase of venom specific IgG1 and IgG4 antibodies, while IgG2 showed an insignificant increase only in some patients. Persistent high levels of IgG4 with respect to decreasing levels of IgG1 were observed only after prolonged treatment. PMID- 3325821 TI - Human neutrophil plasma membrane. Specific labelling, topological distribution of proteins and surface antigen detection. AB - We describe here the major protein components of a highly purified human neutrophil plasma membrane fraction analyzed by uni- and two-dimensional gel electrophoresis, as well as their glycoprotein nature as determined by PAS staining, [125I]-Con A binding and [3H]-sodium borohydride labelling. A polypeptide of about 150 kDa appeared as the main Con A binding protein. The topology of the polypeptides has also been determined by protein labelling from the outside of the cell surface by lactoperoxidase catalyzed iodination and from within the bilayer by using the hydrophobic reagent [125I]-iodonaphtylazide. The antigenic features of some cell surface polypeptides have also been determined by the use of monoclonal antibodies. In this context we have detected by immunoprecipitation in human neutrophils the antigen MAC 120, previously found in monocytes and putatively associated with antigen presenting function. PMID- 3325822 TI - Replication and segregation of plasmids containing cis-acting regulatory sites of silent mating-type genes in Saccharomyces cerevisiae are controlled by the SIR genes. AB - In Saccharomyces cerevisiae, two cis-acting regulatory sites called E and I flank the silent mating-type gene, HMRa, and mediate SIR-dependent transcriptional repression of the a1-a2 promoters. It has been shown previously that the E and I sites have plasmid replicator (ARS) activity. We show in this report that the ARS activity of the E and I sites is governed by the SIR genotype of the cell. In wild-type cells, a plasmid carrying the E site from HMRa (HMR E) in the vector YIp5 exhibited very high mitotic stability at a copy number of approximately 25 per cell. However, in sir2, sir3, or sir4 mutants, plasmids with HMR E had the low mitotic stability characteristic of plasmids containing ARS1, a SIR independent replicator. Elevated mitotic stability of plasmids that carry HMR E is due to a segregation mechanism provided by SIR and HMR E. In sir2 and sir4 mutants, the plasmid copy number was significantly lowered, suggesting that these gene products also participate in the replication of plasmids carrying HMR E. The phenotype of point mutations introduced at an 11-base-pair ARS consensus sequence present at HMR E indicated that this sequence is functional but not absolutely required for autonomous replication of the plasmid and that it is not required for SIR-dependent mitotic stabilization. A plasmid carrying both a centromere and HMR E exhibited reduced mitotic stability in wild-type cells. This destabilization appeared to be due to antagonism between the segregation functions provided by the centromere and by HMR E. PMID- 3325823 TI - Protease B of the lysosomelike vacuole of the yeast Saccharomyces cerevisiae is homologous to the subtilisin family of serine proteases. AB - The PRB1 gene of Saccharomyces cerevisiae encodes the vacuolar endoprotease protease B. We have determined the DNA sequence of the PRB1 gene and the amino acid sequence of the amino terminus of mature protease B. The deduced amino acid sequence of this serine protease shares extensive homology with those of subtilisin, proteinase K, and related proteases. The open reading frame of PRB1 consists of 635 codons and, therefore, encodes a very large protein (molecular weight, greater than 69,000) relative to the observed size of mature protease B (molecular weight, 33,000). Examination of the gene sequence, the determined amino-terminal sequence, and empirical molecular weight determinations suggests that the preproenzyme must be processed at both amino and carboxy termini and that asparagine-linked glycosylation occurs at an unusual tripeptide acceptor sequence. PMID- 3325824 TI - A normal mitochondrial protein is selectively synthesized and accumulated during heat shock in Tetrahymena thermophila. AB - We have identified and purified a 58-kilodalton protein of Tetrahymena thermophila whose synthesis during heat shock parallels that of the major heat shock proteins. This protein, hsp58, was found in both non-heat-shocked as well as heat-shocked cells; however, its concentration in the cell increased approximately two- to threefold during heat shock. The majority of hsp58 in both non-heat-shocked and heat-shocked cells was found by both cell fractionation studies and immunocytochemical techniques to be mitochondrially associated. During heat shock, the additional hsp58 was found to selectively accumulate in mitochondria. Nondenatured hsp58 released from mitochondria of non-heat-shocked or heat-shocked cells sedimented in sucrose gradients as a 20S to 25S complex. We suggest that this protein may play a role in mitochondria analogous to the role the major heat shock proteins play in the nucleus and cytosol. PMID- 3325825 TI - Functional domains of SIR4, a gene required for position effect regulation in Saccharomyces cerevisiae. AB - The product of the Saccharomyces cerevisiae SIR4 gene, in conjunction with at least three other gene products, prevents expression of mating-type genes resident at loci at either end of chromosome III, but not of the same genes resident at the MAT locus in the middle of the chromosome. To address the mechanism of this novel position effect regulation, we have conducted a structural and genetic analysis of the SIR4 gene. We have determined the nucleotide sequence of the gene and found that it encodes a lysine-rich, serine rich protein of 152 kilodaltons. Expression of the carboxy half of the protein complements a chromosomal nonsense mutation of sir4 but not a complete deletion of the gene. These results suggest that SIR4 protein activity resides in two portions of the molecule, but that these domains need not be covalently linked to execute their biological function. We also found that high-level expression of the carboxy domain of the protein yields dominant derepression of the silent loci. This anti-Sir activity can be reversed by increased expression of the SIR3 gene, whose product is normally also required for maintaining repression of the silent loci. These results are consistent with the hypothesis that SIR3 and SIR4 proteins physically associate to form a multicomponent complex required for repression of the silent mating-type loci. PMID- 3325826 TI - Rapid cytoplasmic turnover of c-myc mRNA: requirement of the 3' untranslated sequences. AB - Expression of the c-myc gene can be controlled by transcriptional or posttranscriptional mechanisms (or both), depending on the cell type and the growth conditions. An important mechanism of posttranscriptional regulation is modulation of cytoplasmic c-myc mRNA stability; normal human and murine c-myc mRNAs have cytoplasmic half-lives of 30 min or less. To elucidate the c-myc sequences which impart this unusually high rate of cytoplasmic transcript turnover, we have constructed various deletion and hybrid c-myc genes and analyzed the cytoplasmic stability of the mRNAs produced from them in stably transfected murine fibroblasts. The results indicate that sequences contained within the 5' and 3' ends of the c-myc transcript can affect cytoplasmic stability. Specifically, the 3' untranslated sequences of c-myc exon 3 are required for, but do not ensure, a high rate of transcript turnover in the cytoplasm. Exon 2 coding sequences do not seem to be involved, and exon 1 sequences at the 5' end of the transcript have only a small effect on cytoplasmic transcript stability. The sequences that are primarily responsible for the short c-myc RNA half-life were localized to a region of 140 bases in the 3' untranslated region. PMID- 3325827 TI - Induction of neurite formation in PC12 cells by microinjection of proto-oncogenic Ha-ras protein preincubated with guanosine-5'-O-(3-thiotriphosphate). AB - Rat pheochromocytoma (PC12) cells differentiate to neuronal cells in response to nerve growth factor. It has been shown that microinjection of oncogenic but not proto-oncogenic p21 protein induces morphological differentiation in PC12 cells (D. Bar-Sagi and J. R. Feramisco, Cell 42:841-848, 1985). In this paper we describe a recombinant human proto-oncogenic Ha-ras protein which can effectively induce neurite extension of PC12 cells when microinjected as a complex with guanosine-5'-O-(3-thiotriphosphate). The protein was found to be less effective when complexed with GTP. On the other hand, an oncogenic ras protein coinjected with guanosine-5'-O-(2-thiodiphosphate) was entirely inactive. These results indicate that the binary p21-GTP complex, but not the p21-GDP complex, is effective in inducing differentiation in PC12 cells, irrespective of the oncogenic or the proto-oncogenic protein. PMID- 3325829 TI - Heat-induced expression of albumin during early stages of rat embryo development. AB - An examination of heat-induced expression of proteins in tissues from adult and embryonic liver in rats shows that albumin, which is constitutively expressed in adult liver and is not synthesized in embryos before 16 days of gestation, appears in liver cells at earlier stages of development upon heat shock. On the basis of available evidence for the expression of heat shock proteins at distinct stages of development and on the basis of our findings, it may be argued that there could be common molecular events taking place during development and as a result of heat shock. We suggest also that one of the consequences of heat shock could be an internal change of pH within the cell which, in turn, might trigger alterations in gene expression. PMID- 3325830 TI - Cross-idiotypic specificity among human rheumatoid factors. PMID- 3325828 TI - Plasminogen activator inhibitor 2: regulation of gene transcription during phorbol ester-mediated differentiation of U-937 human histiocytic lymphoma cells. AB - We have isolated and sequenced two cDNA clones coding for plasminogen activator inhibitor 2 (PAI-2). The cDNA was used to study the regulation of PAI-2 gene transcription by the tumor-promoting phorbol ester phorbol 12-myristate 13 acetate in the human histiocytic lymphoma cell line U-937. The tumor promoter caused a transient, 50-fold increase of PAI-2 gene transcription. PMID- 3325831 TI - Analyses of human rheumatoid factors with anti-idiotypes induced by synthetic peptides. PMID- 3325832 TI - Anti-idiotype antibodies reveal the existence of somatic mutation in human B cell lymphoma. PMID- 3325834 TI - Henry Kunkel. In memoriam. PMID- 3325833 TI - Jacques Oudin. In memoriam. PMID- 3325835 TI - Autoimmune network. PMID- 3325836 TI - Idiotypes and anti-idiotypes of human autoantibodies to the acetylcholine receptor in myasthenia gravis. PMID- 3325837 TI - [Does the IIa hip need treatment? Results of a longitudinal study of sonographically controlled hips of infants less than 3 months of age]. AB - In a randomized retrospective study we followed hips classified as Type II a by ultrasound. The classification as "Type IIa" only was found inadequate. It is important to further differentiate the so-called physiologically immature hip, namely to distinguish between joints that, while immature, are appropriate for age [Type IIa(+)], and those hips with a maturation deficit exceeding a tolerable degree [Type IIa(-)]. The follow-up showed that hips classified as Type IIa(-) and treated before the age of 6 weeks had a clearly better healing result than the hips treated only after the sixth week. Thus, to achieve optimal healing and to keep to a minimum the dysplasias requiring treatment after 3 months' age, an ultrasound study of the hip should be done as early as possible. The total percentage of ultrasonically recognized abnormal joints requiring treatment (independently of the patient's age) was 6.6%. This corresponds to the regional average before the advent of ultrasound. However, because of extensive very early screening in our area, we found not a single hip dislocation later then at the age of 10 weeks during the last 2 years. PMID- 3325838 TI - [Is hip sonography in premature infants necessary as a screening procedure?]. AB - Screening sonography of the hip in 132 premature infants indicates that prematurity is not a risk for congenital dysplasia/dislocation of the hip. However, for reasons explained in the text, screening should be carried out before discharge from hospital. Follow-up examinations are necessary only for infants with known risk factors for dysplasia/dislocation of the hip. PMID- 3325839 TI - [Acute focal bacterial nephritis in childhood]. AB - The clinical findings and sonographic observations in four patients with AFBN in childhood are described. AFBN in childhood is an acute interstitial nephritis presenting with septicaemia. The patients show a rapid deterioration of condition, weight loss, flank pain and often leucocyturia without detection of bacteria. The diagnosis is confirmed by renal sonography, showing typical focal alterations. Sonographic follow-up is important to prove the diagnosis. Even without detection of bacteria intravenous broad-spectrum antibiotic therapy is required. The antibiotic should be active against gram-negative organisms and Staphylococci. Medication should be given for 2-3 weeks. After adequate treatment the clinical condition will improve within a few days whereas sonographic alterations return to normal after 2-4 weeks. In childhood, a bacterial infection of other organs preceding AFBN is more common than anomalies of the urinary tract as predisposing factors. Therefore in most cases a hemotogenous infection must be presumed and its focus discovered and eliminated by appropriate antibiotics since otherwise AFBN may recur. PMID- 3325840 TI - [Clinical variants of idiopathic hypercalciuria in children]. AB - Out of five children with hypercalciuria, four had nephrocalcinosis and one recurrent bladder calculi. Two out of four patients with nephrocalcinosis (patients 1 and 2) had the "hyperprostaglandin E syndrome" and the other two (patients 3 and 4, siblings) had the Royer syndrome (osteopathy, dwarfism, secondary hyperparathyroidism). Treatment with hydrochlorothiazide is effective in patients without increased urinary excretion of prostaglandin, whereas patients with increased prostaglandin excretion respond better to indomethacin therapy. PMID- 3325842 TI - Rapid identification of the two varieties of Cryptococcus neoformans by D-proline assimilation. PMID- 3325841 TI - A series of serological tests for the detection of antigens and specific antibodies in deep-seated candidosis: experimental aspects. PMID- 3325843 TI - [Oxiconazole in dermatomycosis--a double-blind, randomized therapy compared with bifonazole]. PMID- 3325845 TI - [A case of systemic lupus erythematosus associated with an aneurysm of the lenticulostriate artery]. AB - We describe a patient with established systemic lupus erythematosus (SLE) in whom an intracerebral hemorrhage developed secondary to a ruptured aneurysm of the lenticulostriate artery (LSA). A 24-year-old woman with a four-year history of SLE was admitted to the department of internal medicine of Iwate Medical University for the treatment of lupus nephritis in 1985. She suddenly complained of severe headache and nausea, and soon lost consciousness. The computed tomographic scan revealed intracerebral hemorrhage in the left front-temporal region and subarachnoid hemorrhage. Left common carotid angiography demonstrated a 3 X 3 mm aneurysm of the LSA and displacement of other LSAs and anterior cerebral artery. The incidence of intracerebral hemorrhage in SLE was about ten percent in the reported central nervous system SLE, and it seemed that the prognosis of SLE with intracerebral hemorrhage was poor. The mechanisms of the intracerebral hemorrhage and the aneurysmal formation in SLE seemed to be due to lupus angiitis, but without clinical, radiologic and pathologic correlation. In operation, a ruptured aneurysm without neck was found in LSA and extirpated. In the pathological study, there was transmural angiitis, which fibrinoid necrosis, elastic tissue disruption and infiltration of inflammatory cells were found. Inflammatory cells were chiefly lymphohistiocytic with some polymorphonuclear leukocytes. It seemed that pathologic studies confirmed transmural angiitis with secondary aneurysm formation. PMID- 3325844 TI - Salidiuretic action of the calcium antagonist nitrendipine in dogs. AB - In an attempt to define the effects of a calcium antagonist, nitrendipine, on renal function, intrarenal hemodynamics, and renin release, we infused the drug into the renal artery of anesthetized dogs. Infusion of nitrendipine at a rate of 5 micrograms/min in both hydropenic and hydrated dogs resulted in a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow and renin release, with no change in systemic blood pressure, indicating a significant renal vasodilation. The urinary excretion rate of sodium increased by the same proportion as that of calcium. The intrarenal blood flow as measured by hydrogen washout rate showed that the outer cortical flow increased by the same proportion as the inner cortical flow. During nitrendipine infusion, free water reabsorption rate (TcH2O) in hydropenic dogs or free water clearance (CH2O) in hydrated dogs increased in proportion to the urine flow. Neither the ratio of TcH2O nor that of CH2O to osmolar clearance changed throughout the experiment. These data suggest that nitrendipine may not inhibit sodium transport in the medullary portion of the ascending limb of Henle and may induce an enhancement of the delivery of sodium to the Henle loop. Thus, nitrendipine exerts its diuretic and natriuretic actions via the alteration of renal hemodynamic and the inhibitory effect on proximal sodium reabsorption. PMID- 3325846 TI - [Chronic calcified subdural hematoma--report of a case]. AB - An 82-year-old woman was admitted to the Department of Neurosurgery, Saiseikai Fukuoka General Hospital with complaints of persistent headache and left hemiparesis. Neurological examination on admission revealed mild left hemiparesis with hyperreflexia. However, no choked disc nor pathological reflexes were noted. Roentgenograms of the skull showed thickening of the bone in the right temporoparietal region with intracranial calcification. CT showed a large right frontoparietal mixed dense space-occupying lesion bordered by a high dense calcified rim. The right lateral ventricle was compressed while the left exhibited a deviation to the left. Furthermore, thickening of the right frontal and parietal bone around the margin of mass was noted. The patient was operated upon under the diagnosis of calcified chronic subdural hematoma. A large osteoplastic flap was turned down on the right front parietal area and hypertrophy of the skull, especially around the hematoma, was noticed. Over the dura just beneath the hypertrophic lesion of the calvaria, a soft, reddish granulation tissue was noted. The dura was stripped easily from the outer membrane. The capsule was opened and the content was found to be of compact consistency, screeching when cut, and it appeared to be filled with large clots, not all homogeneously organized and made out of a substance composed of reddish yellow material. The inner membrane was removed except for the frontal lesion where remarkable adhesion to the arachnoid membrane was noted. The postoperative course was uneventful. At the time of the patient's dismissal, her symptoms had completely disappeared. Histologically, the granulation tissue to be the bone marrow consisted of three hematopoietic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325847 TI - Pharmacological protection against the toxicity of N-methyl-D-aspartate in immature rat cerebellar slices. AB - In order to delineate the pharmacological characteristics of the toxicity of N methyl-D-aspartate (NMDA), slices of cerebellum from 7-day old rats were incubated with NMDA, together with various putative protective agents. These comprised three different groups: (i) a competitive receptor antagonist (kynurenic acid), (ii) direct (cobalt ions, flunarizine) and indirect (taurine) calcium entry blockers, (iii) cyclo-oxygenase inhibitors (indomethacin and acetylsalicylic acid) and a blocker of calcium-activated, neutral proteases (leupeptin). When the slices were incubated for 30 min in medium containing 100 microM NMDA, postmigratory granule cell nuclei were rounded and swollen. After 90 min of recovery in normal medium, the nuclei were pyknotic and the cells were irreversibly injured. As expected, these changes were completely blocked by kynurenate, indicating that NMDA receptors mediate the cell death. Cobalt ions abolished the acute toxicity of NMDA, but after recovery, some granule cell nuclei were swollen. This effect could be attributed to the toxicity of cobalt ions and not to delayed toxicity of NMDA. The other inhibitors of the uptake of calcium, flunarizine and taurine, did neither affect acute nor persistent toxicity of NMDA. These results support the previous finding that the toxicity of NMDA is calcium-dependent and that organic calcium channel blockers are ineffective against NMDA-induced uptake of calcium. Leupeptin had no effect on the toxicity of NMDA, suggesting that calcium-activated proteolysis was not the crucial event in excitotoxic necrosis. Indomethacin, but not acetylsalicylic acid, prevented neuronal degeneration provoked by NMDA, but only in very large concentrations (greater than or equal to 100 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325848 TI - Craniopagi: anatomical characteristics and classification. AB - The incidence, embryology, anatomical features of the site of junction, associated abnormalities, and survival of the 79 craniopagi reported from 1496 to 1987 have been reviewed. All craniopagi upon whom sufficient information is available have been classified on the basis of the deepest shared anatomical structure. PMID- 3325849 TI - Surgical division of craniopagi. AB - The world's surgical experience on the division of craniopagi is reviewed, and a new case is reported. The problems, including ethical considerations, that must be addressed in selecting patients for operation and in preparing for the procedure are discussed in detail. Hemodynamic stability and the problem of intraoperative gravitational distortion of the brain are addressed. The importance of careful planning is stressed. Survival of the 31 craniopagi after operation is discussed in relation to types of junction. PMID- 3325850 TI - Clinicopathological relations of cerebral cavernous angiomas: observations in eleven cases. AB - Eleven cases of cerebral cavernous angiomas (cavernomas) were observed within a period of 3 years. Two patients presented with cerebral hemorrhage, five with epilepsy, three each with a progressive focal neurological deficit, and one with papilledema. The unruptured lesions had a heterogeneous density on computed tomography with relatively little contrast enhancement. Two lesions contained major cysts. In one of these cases, the cyst measured 5.5 cm in diameter, had an enhancing membrane, and was surrounded by brain edema. Angiography did not show hypervascularity in any instance. During exploration and histological processing, special attention was paid to signs of previous silent hemorrhages and to the degree of encapsulation of the lesion. Iron deposits (signs of previous hemorrhages) were seen to varying degrees inside all cavernomas as well as in the surrounding gliotic cerebrum, and a causal relation between iron deposits and epileptic seizures seems likely. Encapsulation was minimal with the ruptured cavernomas and particularly prominent with the cystic lesions. The membrane of the giant cystic lesion with peripheral brain edema had a histological structure similar to that of the membranes of chronic subdural hematomas. It is suggested that continuous growth of cavernoma cysts is the result of recurrent hemorrhages from sinusoids of the malformation and from the neocapillary network of the cyst membranes. PMID- 3325851 TI - Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature. AB - Since the senior author's (J.E.A.) first report in 1972 of the use of deep brain stimulation (DBS) to control chronic pain, electrodes for DBS have been implanted in 141 patients. Of reported series, this one has the largest number of patients and the longest period of follow-up. The mean age of patients in this study was 51.2 years. The mean length of follow-up was 80 months. Patients had experienced pain for a mean period of 65 months before DBS was attempted; all patients had exhausted other medical and surgical therapies. For the purposes of this study, pain states were characterized as being either nociceptive or deafferentation in nature. Nociceptive pain was treated primarily by stimulation of the periaqueductal or periventricular gray, and deafferentation pain was treated primarily by stimulation of the sensory thalamus. Eighty-four patients were treated for deafferentation pain, which included the thalamic pain syndrome (25 cases), peripheral neuropathic pain (16 cases), anesthesia dolorosa (12 cases), paraplegia pain (11 cases), postcordotomy dyesthesia (5 cases), phantom limb pain (5 cases), thoracic neuralgia (4 cases), and miscellaneous pain states (6 cases). We treated 57 patients with nociceptive pain states, 51 for low back and skeletal pain and 6 for pain from the invasion of cancer. Initial relief of pain was obtained by 83 patients (59%). After the mean follow-up period of 80 months, 42 patients (31%) continued to obtain significant pain relief with DBS. Some pain states, particularly anesthesia dolorosa and paraplegia pain, did not seem to respond to DBS. Major complications of therapy included wound infection (12%) and intracranial hemorrhage (3.5%); there was one death in the series (0.7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325852 TI - Angiographic revascularization of the brain after encephaloduroarteriosynangiosis: a case report. AB - Preoperative and postoperative angiograms of a 13-year-old Japanese girl with moyamoya disease are compared. She underwent an indirect extracranial/intracranial bypass operation called encephaloduroarteriosynangiosis (EDAS). Post-EDAS angiograms clearly show revascularization of the brain through the donor scalp artery and decrease in moyamoya vessels, leptomeningeal anastomoses, and preexisting spontaneous transdural anastomoses. PMID- 3325853 TI - Topographic localization of neuromedin U-like structures in the rat brain: an immunohistochemical study. AB - The distribution of neuromedin Us, uterus-stimulating and hypertensive peptides newly identified in porcine spinal cord, was examined in the rat brain by the indirect immunofluorescent method. Neuromedin U-like immunoreactive structures were found to be unevenly distributed in the neuronal system. Neuromedin U-like immunoreactive neurons were present in the cranial motor nuclei, reticular nuclei, nucleus vestibularis lateralis, trigeminal sensory nuclei, colliculus superior and inferior, lemniscus lateralis, nucleus pontis, nucleus ruber, zona incerta, substantia innominata, horizontal limb of the diagonal band and cerebral cortex. The immunoreactive fibres were found in the above areas, particularly near the labelled cells, forming a fibre plexus with various intensities of immunoreactivity. In addition, dense plexuses were also seen in the nucleus reticularis thalami, nucleus ventralis posteromedialis, nucleus ventralis posterolateralis, nucleus tegmentalis dorsalis and ventralis, vertical limb of the diagonal band, nucleus olivaris superior, and nucleus pontis. In the first six structures, no labelled neurons were present and in the remaining structures, a few scattered neurons were noted. This indicates that these fibres are probably of extrinsic origin. PMID- 3325854 TI - Grafting genetically modified cells to the brain: possibilities for the future. AB - Diagnostic and therapeutic approaches to disorders of the central nervous system (CNS) are particularly difficult to develop because of the relative inaccessibility of the mammalian brain to study and chemical treatment, the complexity and interconnectedness of CNS subsystems, and the profound and continued lack of fundamental understanding of the relationship between structure and function in the CNS. Neural grafting in the CNS has recently suggested a potential approach to CNS therapy through the selective replacement of cells lost as a result of disease or damage. Independently, studies aimed at direct genetic therapy in model systems have recently begun to suggest conceptually new approaches to the treatment of several kinds of human genetic disease, especially those caused by single-gene enzyme deficiencies. We suggest that a combination of these two approaches, namely the grafting into the CNS of genetically modified cells, may provide a new approach toward the restoration of some functions in the damaged or diseased CNS. We present evidence for the feasibility of this approach, including a description of some current techniques for mammalian cell gene transfer and CNS grafting, and several possible approaches to clinical applications. PMID- 3325855 TI - A quantitative approach to cross-reaction problems in immunocytochemistry. PMID- 3325856 TI - [Cardiovascular and metabolic effects of controlled hypotension with isoflurane in neurosurgery]. PMID- 3325858 TI - [Anesthesiologic problems in relation to advanced neurosurgical technology]. PMID- 3325859 TI - The biosynthesis of polyketides. PMID- 3325857 TI - [Changes in central venous pressure and intracranial pressure following the introduction of positive end-expiratory pressure ventilation in supine and seated position during neurosurgery]. PMID- 3325860 TI - Diterpenoids. PMID- 3325861 TI - Indolizidine and quinolizidine alkaloids. PMID- 3325862 TI - The biosynthesis of plant alkaloids and nitrogenous microbial metabolites. PMID- 3325863 TI - The biosynthesis of porphyrins, chlorophylls, and vitamin B12. PMID- 3325864 TI - Catecholamines and attention. I: Animal and clinical studies. AB - One important function of the catecholamine innervation of the cerebral cortex may be the control of attention. Of particular interest are the catecholamine projections to the cerebral cortex from the reticular formation, namely the dopamine neurons of the ventral tegmentum of the midbrain and the noradrenergic neurons of the locus coeruleus in the upper pons. Animal studies implicate noradrenaline and dopamine in a wide range of attention-related behaviours involving search and exploratory activity, distractibility, response rate, discriminability and the switching of attention. Most human studies come from the clinical literature relating to schizophrenia, Parkinson's disease and attention deficit disorder. An association has been claimed in each of these conditions between abnormal catecholamine activity (in particular dopamine) and attentional dysfunction. In particular, difficulty with the attachment of appropriate responses to environmental stimuli, akin to those observed in animals with lesions to central dopamine pathways, indicates a role for dopamine in response selection processes. Overall, the animal and human studies reviewed indicate a role for central noradrenaline and dopamine in the early and late processing of information, respectively. PMID- 3325865 TI - Catecholamines and attention. II: Pharmacological studies in normal humans. AB - Part I of this review [17] found evidence from animal and clinical studies of a role for catecholamines in the control of attention. This part of the review examines the results of a systematic study of the acute effects of a number of catecholamine active drugs on measures of attention in normal adults. The results are interpreted within the context of a general capacity model of information processing in which level of arousal determines the capacity to process stimulus information and level of activation the capacity for processing response demands. Whilst the dopamine antagonist, droperidol, and the alpha agonist, clonidine, had similar effects on behavioural indices of processing capacity and reports of the degree of effort required to carry out processing, they differentially affected subjective state and measures of activation and arousal. These differences provide some support for the hypothesis that central noradrenaline and dopamine modulate the capacity for early and late processing of information, respectively, in humans. PMID- 3325867 TI - [Ultrasonic echoosteometry in metaepiphyseal fractures]. PMID- 3325866 TI - AL721, a novel membrane fluidizer. AB - AL721, which is a novel lipid mixture extracted from egg yolks, is believed to be a therapeutic pharmacologic agent. AL721 interacts with membranes of various types of cells with a common mode of action. AL721 modifies cellular membrane composition and fluidity through passive extraction and/or exchange of cholesterol. Physiologically diminished cell function due to rigidification of its membrane is reversible both in vitro and in vivo by AL721. Fluidization of aged membranes with AL721 has been shown to restore brain serotonin receptor function both in vitro and in vivo. AL721 can also successfully restore deficient immune responsiveness of lymphocytes to mitogen stimulation in aged subjects. Drug tolerance to morphine and ethanol develops upon elevation of the viscosity of neuronal cell membranes in order to counteract the fluidization effect of the drug. Treatment of rigidified cellular membranes with AL721 in vivo can markedly reduce withdrawal symptoms. The virucidal effect of AL721 on the human immunodeficiency virus is believed to operate by lowering of viral membrane cholesterol thus interfering with the binding of the viral antigen to the host cell. Non-toxicity of AL721 is clearly demonstrated in animal and human safety studies. PMID- 3325868 TI - [Surgical treatment of hallux valgus]. PMID- 3325869 TI - [A method of correcting skin defects in the areas of the Achilles tendon and posterior surface of the heel]. PMID- 3325871 TI - [Alcoholic intoxication and injuries (review of the literature)]. PMID- 3325870 TI - [Instrumental methods in the diagnosis of injuries of the major blood vessels of the extremities]. PMID- 3325873 TI - [Suicidal behavior--from the clinician's view]. PMID- 3325872 TI - [Early stomach cancer--results and doubts 15 years later]. PMID- 3325874 TI - [Diagnosis of cystic fibrosis based on restriction fragment length polymorphism of DNA]. PMID- 3325875 TI - Elevated expression of an exogenous c-myc gene is insufficient for transformation and tumorigenic conversion of established fibroblasts. AB - Two established rat fibroblast lines, differing only by their number of generations in culture, show dramatically different responses to the elevated c myc expression delivered by an efficient murine c-myc retrovirus vector. Thus, a late passage (60 generation) FR3T3 line acquires a transformed and tumorigenic phenotype upon introduction of this activated c-myc gene as indicated by its altered morphology, high efficiency of focus formation, soft agar clonability, saturation density in monolayer culture, and short latency of tumorigenicity in syngeneic hosts. Remarkably, none of these characteristics, except for an increased refractility in monolayers and an epidermal growth factor (EGF) dependent agar clonability, were observed in a variety of early passage (10 generation) FR3T3 c-myc clones. BALB/c A31 fibroblasts transfected with this c myc retroviral vector behaved essentially the same as the FR3T3 early line except for their inability to grow in suspension in response to EGF. However, transformation and tumorigenic conversion of each of these three fibroblast lines was achieved by an activated ras oncogene. Hence, elevated c-myc expression is insufficient for transformation of established fibroblasts but depends upon other acquired cooperating functions which are not necessary for ras induced transformation. We also demonstrate that endogenous c-myc expression remains unaffected even in clones expressing a 100-fold excess of exogenous c-myc RNAs demonstrating that c-myc autoregulation is not operative in these cells. PMID- 3325876 TI - Detection of PDGF-2 homodimers in human tumor cells. AB - The v-sis oncogene encodes a protein structurally and functionally related to human platelet-derived growth factor (PDGF). In the present studies, we show that the primary translational product of the human sis proto-oncogene is a 26-kd protein, p26c-sis. This product is processed to yield a disulfide-linked homodimer, p56c-sis, which is further processed to a 35,000-dalton dimer, p35c sis. Like the v-sis gene product, the PDGF-2 precursor undergoes N-linked glycosylation, implying its processing through the endoplasmic reticulum. The PDGF-2 product was shown to possess functional properties of PDGF. Whereas lysates of control COS-1 cells lacked mitogenic activity, lysates of COS-1 cells transfected with a c-sis/PDGF-2 expression vector specifically stimulated DNA synthesis of quiescent fibroblasts. Moreover, this activity was completely inhibitable by PDGF antibody. Identical forms of the sis/PDGF-2 product were identified in human tumor cells that expressed c-sis/PDGF-2 transcripts. These proteins were shown to be specifically associated with the membrane component of the tumor cells and were not detectably secreted into the culture medium. These findings support the concept that expression of the sis/PDGF-2 product in human cells responsive to its proliferative actions can be an important step in the processes leading to malignancy. PMID- 3325877 TI - Bryostatin induces changes in protein kinase C location and activity without altering c-myc gene expression in human promyelocytic leukemia cells (HL-60). AB - When human promyelocytic leukemia cells (HL-60) are induced by phorbol esters to differentiate to macrophages, the process is accompanied by immediate activation of protein kinase C (PK-C) in the cytoplasm and later changes in DNA and RNA synthesis. Although these events are temporarily related, it remains unclear how activation of this protein kinase leads to changes in nuclear transcription. In this study, we find that bryostatin, a macrocyclic lactone which does not induce differentiation of HL-60 cells but activates PK-C, mimics the effects of phorbol esters on protein phosphorylation and PK-C location. Treatment of HL-60 cells with bryostatin stimulates phosphorylation of the surface transferrin receptor and in the cytoplasm of five proteins having the molecular weights of 17-43 kDa over the same time course as that stimulated by phorbol esters. Similarly, prolonged treatment with bryostatin, like that with phorbol esters, causes the loss of all cellular PK-C activity. Unlike the phosphorylation studies, bryostatin treatment, over a 1-100 nM concentration range and for varying lengths of time, did not affect HL-60 c-myc RNA levels, while phorbol ester treatment rapidly decreased c-myc RNA levels. These data suggest that neither the activation of PK-C and the phosphorylation of specific substrates nor the loss of total cellular PK-C activity from HL-60 cells is sufficient to induce marked decreases in c-myc levels and differentiation of HL-60 cells. PMID- 3325878 TI - N-methyl-N-nitrosourea-induced transformation of rat urothelial cells in vitro is not mediated by activation of ras oncogenes. AB - Adult rat urothelial cells were transformed in vitro following treatment with a single dose of N-methyl-N-nitrosourea (MNU) or MNU treatment followed by promotion with sodium saccharin. This in vitro transformation process involves multiple steps: slow-growing 'pre-neoplastic' epithelial foci are induced 70-100 days after MNU treatment and from such foci rapidly proliferating immortal cell lines were established, some of which became tumorigenic after a further latent period. A series of epithelial cell lines and a single fibroblast cell line established in this way were analysed for the presence of transforming genes by DNA transfection into NIH3T3 cells. None of the epithelial cell lines induced foci in a focus formation assay. The single non-epithelial line induced foci and was found to contain an activated c-Ki-ras gene with a G----A transition in codon 12. To assay for the possible presence of transforming genes which were not active in a focus formation assay, two of the epithelial lines were analysed further by co-transfection with a dominant selectable marker, followed by selection and inoculation into nude mice. No tumours were induced within the latent period for tumour production by control cells transfected with NIH3T3 cell DNA (40-60 days). These results suggest that there is cell type specificity for oncogene activation during in vitro rat bladder transformation initiated by a single carcinogen and that ras gene activation is not a necessary step in urothelial transformation in vitro. PMID- 3325879 TI - Metastatic potential of SP1 mouse mammary adenocarcinoma cells is differentially induced by activated and normal forms of c-H-ras. AB - The mouse mammary adenocarcinoma cell line SP1 was transfected with either the activated T24-H-ras or the normal c-H-ras gene and assessed for metastatic potential in syngeneic CBA/J or nude mice. Unlike the parental control cells, which were tumorigenic but unable to metastasize from a subcutaneous site, all SP1 transfectants expressing the T24-H-ras gene were able to metastasize (predominantly to the lung). In contrast, a much smaller fraction of the clones obtained following transfection with either normal c-H-ras or pSV2neo were metastatic and, significantly, elevated expression of the c-H-ras proto-oncogene did not correlate with acquisition of metastatic potential. We conclude that activated and normal forms of the c-H-ras gene differ in their ability to confer metastatic potential to SP1 mouse mammary adenocarcinoma cells. PMID- 3325880 TI - Expression of normal and mutant ras proteins in human acute leukemia. AB - The expression of normal and mutant ras genes in human acute leukemias was assessed by the direct analysis of p21ras polypeptides, using immunoprecipitation with monoclonal antibodies. High-resolution two-dimensional gel electrophoresis permits the identification of a wide array of activated ras alleles encoding proteins with single amino acid substitutions at any of several positions. The products of three ras genes, H-ras, N-ras, and K-ras, were detected in each of 33 specimens of fresh leukemic cells. The normal K-ras and N-ras polypeptides were substantially more abundant than H-ras p21 in all samples. In over three-fourths of the cases the total amount of p21ras exceeded that seen in control hematopoietic cell lines. The level of ras expression did not correlate simply with clinical parameters, although the two samples with the most abundant p21ras were obtained from patients with relapsed T-cell acute lymphocytic leukemia (ALL). Abnormal p21ras, consistent with oncogenic activation, was found in eight patients. Six of 11 samples from acute myelocytic leukemia (AML) patients displayed a mutant N-ras p21, while only one of 20 ALL specimens had abnormal N ras, and one had a mutant H-ras. In every case the mutant protein comprised a minority of total p21ras. In two T-cell ALL cell lines both normal and activated N-ras gene products were expressed at equal levels. By contrast, in five fresh AML samples the abnormal N-ras protein was several-fold less abundant than the normal N-ras p21. This finding implies that only a proportion of leukemic cells in an individual patient may carry the mutant ras oncogene. PMID- 3325881 TI - Novel transforming sequences in human acute myelocytic leukemia cell lines. AB - DNA transfection analyses using the tumorigenicity assay were performed on seven human acute myelocytic leukemia (AML) cell lines. DNAs from all cell lines induced tumors in nude mice. Respective transforming sequences could be identified as activated N-ras genes in AML cell lines THP-1, KG-1 and Rc2a. We observed the transfer of five putative novel transforming sequences from DNAs of cell lines U937, ML-1, HEL and CTV-2. These sequences appear to be unrelated to each other and previously known oncogenes. Transfections containing these transforming genes show distinctive biological and morphological characteristics. Our data suggest that the transforming sequences reported here became activated during the transfection process rather than the AML cell line. PMID- 3325882 TI - Analysis of Fos protein complexes and Fos-related antigens by high-resolution two dimensional gel electrophoresis. AB - Protein complexes containing the c-fos protein (Fos) and (Fos)-related antigens were isolated from serum-stimulated fibroblasts and from nerve growth factor plus benzodiazepine-treated pheochromocytoma (PC12) cells, and investigated by high resolution two-dimensional gel electrophoresis. The results show that Fos is complexed with a basic 39-kDa protein (p39) in fibroblasts, and primarily with an acidic 40-kDa protein (p40) in PC12 cells. Whole cells lysates from both cell types contain p40, suggesting that the interaction of Fos and other cellular proteins is dependent on the differentiated state of the cell. In addition to p39 and p40, a heterogeneous population of polypeptides of approximately 48 kDa are present in Fos complexes isolated from non-denatured extracts of either cell type. These proteins may represent a minor class of Fos-binding proteins. Analysis of extracts prepared under denaturing conditions using antisera raised against a Fos peptide (amino acids 127-152) reveals a series of Fos-related antigens. These antigens are induced, some with a slower kinetics than Fos, in fibroblasts and PC12 cells. Thus, c-fos may represent a marker for a family of genes, some of which are antigenically related, that are part of an early cellular transcriptional response to diverse extracellular stimuli. PMID- 3325883 TI - Primary structure of the met protein tyrosine kinase domain. AB - The primary structure of the protein tyrosine kinase domain of the human met gene has been determined from cDNA clones prepared from transcripts of the activated human met gene. These analyses reveal that the met kinase domain (located on human chromosome 7) possesses unique features that distinguish met from other members of the src family of protein tyrosine kinases. The results also demonstrate that the product of the activated met gene is a fusion protein and that the amino terminal end of this fusion protein, which is encoded by human chromosome 1, exhibits homology to laminin B1. PMID- 3325884 TI - Characterization of the protein product of bcl-2, the gene involved in human follicular lymphoma. AB - A protein corresponding in size to the bcl-2 alpha protein obtained after in vitro transcription and in vitro translation in a rabbit reticulocyte lysate was specifically immunoprecipitated from a human B-cell extract using rabbit polyclonal antiserum raised against a beta-galactosidase/bcl-2 fusion protein. Peptide mapping with V8 protease confirmed the identity of this protein as human bcl-2 alpha. Subcellular fractionation of cellular protein followed by immunoprecipitation showed that the bcl-2 alpha protein is associated with the cell membrane. PMID- 3325885 TI - Different regulation of N- and c-myc expression during phorbol ester-induced maturation of human SH-SY5Y neuroblastoma cells. AB - The mRNA expression of c-myc and N-myc in the human neuroblastoma cell line SH SY5Y was found not to change appreciably during the cell cycle and was also unaffected by proliferative inhibition induced by serum starvation or polyamine depletion. However, an early (0.5-8.0 h post-induction) transient reduction of c- and N-myc transcripts were observed in these cells upon induction to differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment of these neuroblastoma cells with TPA for longer periods (1-8 days), which induces morphological and functional differentiation and growth arrest, was followed by decreased expression of both myc genes. However, the rate of disappearance differed considerably. The N-myc mRNA level was slightly decreased after 4 days and was still detectable 8 days after induction, whereas the c-myc transcript was down-regulated much faster. In contrast, when the cells were exposed to retinoic acid, which results in a maturation along an alternative pathway, the inhibition of N-myc and c-myc expression was similar. The c-fos mRNA expression increased in TPA-treated SH-SY5Y cells and remained high during extended exposure to the drug. The highest c-fos transcript level in induced cells coincided in time with the transient reduction of N-myc and c-myc. Thus, the TPA-induced neuronal differentiation of SH-SY5Y cells was compatible with high c-fos and a substantial N-myc mRNA expression. PMID- 3325886 TI - Isolation and characterization of the c-fos(rat) cDNA and analysis of post translational modification in vitro. AB - c-fos mRNA accumulates to a level of 0.2% of cellular poly(A)-containing RNA 45 min after treatment of rat pheochromocytoma (PC12) cells with 1 mM barium chloride. Several clones of the c-fos(rat) cDNA were isolated from a cDNA library constructed from this RNA population. Nucleotide sequence analysis of a full length cDNA clone reveals striking conservation among the c-fos genes isolated from rat, mouse and human cells, and confirms the c-fos gene structure predicted from an analysis of c-fos genomic clones. Translation of an SP6-derived transcript of the c-fos(rat) cDNA in a messenger-dependent rabbit reticulocyte lysate yields the complete c-fos protein. It undergoes extensive post translational modification in the lysate, particularly in the presence of additional cAMP. The c-fos protein synthesized in vitro appears to be phosphorylated by the cAMP-dependent protein kinase. PMID- 3325888 TI - Beta 2 microglobulin in renal function of patients with jengkol intoxication. PMID- 3325887 TI - Chicken proto-oncogene c-ros cDNA clones: identification of a c-ros RNA transcript and deduction of the amino acid sequence of the carboxyl terminus of the c-ros product. AB - Three overlapping cDNA clones that hybridized to a v-ros probe were isolated from a cDNA library constructed from chicken kidney mRNA. Sequence analysis of these clones showed that they were all derived from c-ros mRNA. Using hybridization probes synthesized from the cDNA clones, a c-ros mRNA transcript of approximately 8.3 kb was detected in chicken kidney RNA, but not in chick embryo fibroblast RNA. The amino acid sequence predicted from the cDNA sequence indicates that the carboxyl terminus of the chicken c-ros protein contains 58 amino acids which are not present in v-ros. The predicted amino acid sequence of the chicken c-ros protein differs by 25% from that of its closest known human counterparts within the tyrosine protein kinase catalytic domain, and by 66% downstream of this domain. Despite these differences, both the chicken and human amino acid sequences share a potential site of tyrosine phosphorylation near their carboxyl termini that is absent from v-ros. PMID- 3325890 TI - [Bioclinical research: basic and applied]. PMID- 3325889 TI - [Pharmacotherapy of different forms of hypertension in childhood]. AB - Plasma volume, total peripheral resistance, and cardiac output are the predominant factors for maintaining adequate blood pressure. However, mineralocorticoid excess, as in certain types of adrenogenital syndrome, an increased plasma volume may lead to hypertension. Renal diseases with activation of the renin-angiotensin-system induce hypertension by augmentation of the total peripheral resistance. Finally, increased cardiac output in the juvenile hyperkinetic syndrome is the primary factor for arterial hypertension. This simplified concept of the pathogenesis of hypertension appears to be helpful for the first choice of three categories of antihypertensive agents, which are diuretics, vasodilators and beta-adrenergic blockers. However, it has to be considered that changing one of the three blood pressure determining parameters may have an effect on the two others counteracting the pharmacotherapeutic intervention. So vasodilatation leads to increased fluid retention and raised plasma volume and/or induces reflex tachycardia with increased cardiac output. Thus, a combined treatment with two or three drugs with different antihypertensive effects are frequently needed. A standard combination may include all three antihypertensive principles, such as hydrochlorothiazide--as a diuretic and a mild vasodilator--and propranolol. When blood pressure level does not return to normal under these antihypertensive regimen despite adequate dosage, a specialist ought to be consulted who may consider additional pharmacointerventions with e.g. a potent direct vasodilator, such as minoxidil, the alpha-adrenergic blocker prazosin, the calcium-antagonist nifedipine or the converting enzyme inhibitor captopril. In case of malignant hypertension transfer of the patient to a specialized center is mandatory. PMID- 3325891 TI - [What has become of preliminary transfusion protocols in kidney transplantation?]. AB - Many studies have demonstrated that pretransplant blood transfusions improved cadaver kidney graft outcome. The nature and the frequency of transfusions induced lymphocytotoxic antibodies depends of sex, previous pregnancies and kidney grafts, and transfusional patterns. This provoked immunisation is not a hindrance to beneficial effects of transfusions. Numerous reports have investigated the responsible mechanism for this effect. Controversial data concern the optimum number of blood units. In a previous prospective study in patients who received anti-lymphocyte globulins as part of immunosuppressive therapy, we have shown that a multiple transfusions policy does not give better results than only one. Recently, the beneficial effect of transfusions has been questioned, either entirely, or for particular patients according to age, sex, immunosuppressive treatment including cyclosporin or not. This leaded us to reassess benefits of transfusions. PMID- 3325892 TI - [Chemiluminescence of phagocytic cells in chronic gingivitis and adult periodontitis]. AB - Measurement of chemiluminescence (CL) produced by phagocytic cells spontaneously or upon stimulation by phorbol myristate acetate (PMA) was performed in patients with gingivitis and adult periodontitis, and in control healthy subjects. The study was performed simultaneously on phagocytic cells obtained from peripheral blood and from gingival blood, and on crevicular leukocytes. An elevated CL production was obtained in quiescent and PMA-stimulated phagocytic cells from peripheral blood in patients with gingivitis or periodontitis compared to non diseased controls. Chemiluminescence produced by unstimulated crevicular phagocytes was similar to that of peripheral blood phagocytes in normal subjects, but it was decreased in periodontitis. Upon PMA stimulation, the CL response of crevicular phagocytes remained low in the three groups of subjects. PMID- 3325893 TI - [Hemorheological disorders linked to alcoholism]. AB - Haemorheological parameters were studied in 138 alcoholic subjects at different stages of the liver disease, compared to non alcoholic liver diseases and controls. Results showed 1) a decrease in whole blood filterability in the three groups of alcoholic patients associated with a decrease in erythrocyte ATP level, 2) an increase in blood and plasma viscosities, 3) morphological alterations visualized by scanning electron microscopy. These disturbances are correlated to the abnormalities of red cell membrane lipids composition: increase in cholesterol/phospholipids ratio, increase in saturated fatty acids and decrease in polyunsaturated fatty acids (arachidonic and linoleic acids). The responsibility of alcohol itself, in the genesis of these disturbances has been demonstrated by acute alcohol drinking experiments in healthy subjects. PMID- 3325894 TI - [Value of computer processing of data acquired by cytofluorometry for biological analyses]. AB - The amount of informations relative to cell analysis generated on a flow cytometer must often be processed on a computer so that accurate and efficient analysis can be performed on the stored data, and have the power to consider complex signal distributions. A Ortho 50H flow cytometer was complemented with a Persona 1600 microcomputer (LogAbax) via an acquisition system directly connected to the photomultiplier assemblies. In the configuration we used, three primary signals are processed and stored simultaneously, thus providing six parameters for each cell. The analysis of the data can be delayed or operated immediately after each acquisition. Turbo Pascal was used for all programming. The implanted programs are available for the processing of histograms relative to immunofluorescence or DNA analyses. They allow the user to operate on data obtained after selecting the cells on a two-parameter basis. Examples of immunofluorescence and DNA analyses obtained on experimental preparations are presented. PMID- 3325895 TI - [Mechanisms of infection and cure]. PMID- 3325896 TI - [Bacteria, host defense mechanisms and antibiotics]. AB - If immunopharmacological studies of antibiotics have to be done, it urgently involves the development of a better knowledge of the relationships existing between the bacterial virulence factors, the non specific and specific host defense mechanisms and the antibiotics. This will lead to a better and deeper analysis of the antibiotics immune targets at the cellular and molecular levels and will produce and validate new in vivo and ex vivo experimental models, being standardized and closed to clinical setting. These two conditions would permit a better choice of antibiotics in infected patients, taking into account all the factors needed for the recovery. PMID- 3325897 TI - [Bacterial adhesion: its consequences in antibiotherapy]. AB - The aim of the present review is to analyze the influence of antibiotics on bacterial adhesion and to anticipate this approach as an alternative possibility of prophylactic or therapeutic interference with the infectious process. Adhesive interactions between bacteria and substratum including solid and cellular surfaces were briefly documented. Bacteria displays a very large variety of adhesins and this implies complex mechanisms in the adhesion process. Anti adhesive therapy must take into account several factors: particularly interference with the colonization of mucosal surfaces by normal flora and phagocytic defense system in which adhesion plays a very important role as well. PMID- 3325898 TI - Effects of antibiotics on bacterial structure and their pathogenicity. AB - Subinhibitory concentrations of beta-lactam antibiotics as well as some other antibacterial agents alter the ultrastructure of bacteria. The separation of replicated genomes of Gram positive cocci is inhibited, and results in clusters of as many as 30 organisms held together by thick cross walls. The separation of the replicated genomes of Gram negative bacilli is also inhibited and results in the formation filaments. These altered forms of bacteria usually exhibit lower pathogenicity than their respective normal counterparts such as; decreased adherence to epithelial cells, higher susceptibility to phagocytosis and decreased output of bacterial enzymes. Contrary to common belief, subinhibitory concentrations do not generate a significant increase in bacterial resistance to the respective drug. PMID- 3325899 TI - Changes in expression of bacterial surface antigens induced by antibiotics and their influence on host defenses. AB - Concomitant with the discovery that a number of antibiotics were able to induce profound morphological changes (increased septation, thickened walls, filamentation) at low concentrations their ability to inhibit bacterial protein/polysaccharide synthesis was determined. In particular toxin and extracellular enzyme biosynthesis could be repressed by the lincosamines, fusidic acid, erythromycin and streptomycin in Staphylococcus aureus, Streptococcus pyogenes, Propionibacterium acnes, Pseudomonas aeruginosa and Escherichia coli. Several of these exoproducts act as antigens associated with microbial virulence and are therefore of importance in pathogenicity. Likewise structural components such as fimbriae in Escherichia coli, M protein in Streptococcus pyogenes, protein A in Staphylococcus aureus and capsule in Bacteroides fragilis and Haemophilus influenzae were not synthesised when the producer bacteria were grown in low concentrations of antibiotic. These products, through their importance as impedins of opsonization and subsequent phagocytosis by white blood cells, are important determinants in the host-parasite relationship. By their loss during drug exposure, potentiation of opsonophagocytosis occurred leading to more rapid killing of the pathogen. The immunogenicity of the antibiotic-damaged bacteria was also changed under these circumstances. PMID- 3325901 TI - [The role of 4-quinolones and antibiotics in the elimination of virulence plasmids of Enterobacteriaceae]. AB - Twenty-six antibiotics belonging to thirteen different chemical families had been tested on seven Enterobacteriaceae harbouring a virulence plasmid (Shigella sonnei, S. flexneri, S. dysenteriae, Escherichia coli (two plasmids). Yersinia and Salmonella dublin). Novobiocin and rifampicin were found to be most efficient eliminating three plasmids of which two come from Shigella. Clindamycin, cotrimoxazole, nifurzide, ciprofloxacin, and tilbroquinol were also efficient, but at lower rate. Four virulence plasmids (from the three Shigella sp and Y. pestis) were eliminated by one or several antibiotics. The frequency of elimination was low (at best 10% bacteria per generation). The plasmid pWR105 from S. sonnei was the less stable. PMID- 3325900 TI - [Effect of antibiotics at subinhibitory concentrations on alpha-hemolysin production in uropathogenic Escherichia coli]. AB - The action of subinhibitory concentrations of seven antibiotics (Mezlocillin, Streptomycin, Tobramycin, Chloramphenicol, Tetracycline, Nalidixic acid and Pefloxacin) on the ability to produce alpha-hemolysin are studied on six strains of uropathogenic E. coli. At CMI 2 most of the antibiotics have an inhibitory action. At lower concentrations Pefloxacin, Tetracycline, Streptomycin (in the decrease order) have still an action. Some variations in determinations are observed in function of the choice of the antibiotics and also in function of the stains of E. coli studied. PMID- 3325902 TI - [Functions of neutrophils in vivo on the human skin. Applications to the study of psoriasis and anti-inflammatory agents]. AB - A reproducible method for sequential study of migration out of human skin, phagocytosis and bactericidal activity of neutrophils is described. Untreated psoriatics exhibit an early increase of chemotactic activity (0-8 h, p less than 0.02) and subsequently a strong inhibition of chemotaxis (8-24 h, p less than 0.01), a slight decrease of phagocytosis and a decrease in bactericidal activity (20 mn, p less than 0.02; 30 mn, p less than 0.003); 60 mn, p less than 0.001; 120 mn, p less than 0.001) as compared with controls. After clearing of skin lesions, the early increased chemotactic activity returned to normal values but the subsequent chemotactic inhibition remains as strong as before treatment. Phagocytosis increased to normal values (p less than 0.02) and bactericidal activity also increased but remained significantly low. The abnormalities were more evident in migrating than in circulating neutrophils, underlining the sensitivity of the described method. Using the same method we have shown that the aromatic retinoid etretinate (Ro 10-9359) and its main metabolite (Ro 10-1670) significantly inhibit the migration of neutrophils from the blood to tissues when applied into skin chambers (0.1 mg/ml) or when given orally (1 mg/kg/day) for 8 days to normal volunteers. This pharmacological property could be closely linked to the antipsoriatic properties of these drugs. PMID- 3325903 TI - [Physiopathology of the mechanism of activation of neutrophils: a future pathway?]. AB - Numerous agonists such as chemotactic factors, phorbol esters, calcium ionophores, arachidonic acid or particles induce a cascade of events associated to oxygen reduction, the oxidative burst, in phagocytes and specially in neutrophils. Diverse transductional pathways involved in the oxidative burst were described. Moreover, various pathologies of the transductional pathways in different cell systems were recently observed. We think that the study of neutrophils constitutes first an excellent model of Cell Biology and second a putative model of the physiopathology of the transductional pathways. PMID- 3325904 TI - [Antibiotics and chemotaxis in agarose. The role of incubation conditions and application to several fluoroquinolones]. AB - Nelson's agarose technique for the in vitro measurement of leukocyte chemotaxis proved to be well suited in the context of pharmaco-toxicological testings, despite several discrepancies in the literature, probably due to varied incubation conditions. Thus, doxycycline (25 micrograms/ml) when added to both the leukocyte suspension and the agarose was shown to exert a significantly more pronounced depressant effect. Using these conditions of improved sensitivity, three fluoroquinolones, i.e. norfloxacin, ofloxacin and pefloxacin (2, 10 or 25 micrograms/ml) failed to depress chemotaxis markedly. PMID- 3325905 TI - [In vitro effect of amphotericin B on polymorphonuclear chemotaxis and large granular lymphocytes with natural killer activity]. AB - Amphotericin B (AB) is known as an inhibitor of PMN chemotaxis. The chemotaxis of "large granular lymphocytes" (LGL) which are hypothesized to be involved in the antifungal defenses has been only recently investigated. Therefore we have studied the effect of AB on the LGL chemotaxis. LGL are prepared by centrifugation of peripheral blood non adherent cells on a discontinuous gradient of Percoll. They are more susceptible than PMN to the toxicity and chemotactic inhibition induced by colloidal suspension of AB Fungizone i.v. whereas the microparticular suspension has no effect. Deoxycholate (DOC) used for the AB solubilization is responsible at high doses of Fungizone i.v. (1 and 10(-1) mg/ml) of the toxic effect observed. The particular size seems to be also important. Morever at the therapeutic concentrations (2 to 4 X 10(-3) mg/ml) only the chemotaxis of PMN and LGL induced by FMLP is reduced whereas there is a stimulation of the PMN response to zymosan. The differences in the susceptibility of LGL and PMN to AB may explain the immunomodulation induced by this drug. PMID- 3325906 TI - [Antibiotics and hematopoiesis: toxicity of beta-lactam on in vitro granulopoiesis]. AB - The neutropenia induced by beta-lactam antibiotics conduct us to study the in vitro effect of these antibiotics on human granulopoiesis. We use a semi-solid medium (agar) with placenta conditioned medium as support of granulo-monocytic progenitors growth. We tested the inhibitory effect of prolonged exposure of bone marrow cells to several classes of beta-lactam antibiotics. We found a dose dependent inhibition in all cases, more pronounced for cephalosporins than for ureido-penicillins. A short (1 hour) exposure was less toxic and could explain the rare occurrence of neutropenia in patients treated with these drugs. PMID- 3325908 TI - [Interactions between macrophages and anti-infective agents]. AB - Direct effects of antimicrobial agents on macrophages functions are not well precised. However, antimicrobials can enhance phagocytosis of bacteria by macrophages in vitro, at subinhibitory concentrations. This enhancement is related to the antibiotic effect. It is dependent of the nature of the antimicrobial agent, of the experimental procedure and some discrepancies appeared in the results. The precise mechanism, effect on the bacterial wall, or on the bacterial protein synthesis is uncertain. The third type of interaction concerns the intracellular penetration and activity of antimicrobial agents within macrophages. In a human monocyte-derived macrophage model, the intracellular growth of Legionella pneumophila was inhibited by erythromycin, rifampicin and fluoroquinolones at concentrations clearly lower than their MICs; doxycycline and cotrimoxazole were inhibitory at concentrations closed to their MICs. Cefoxitin was not inhibitory even at high concentrations despite a low MIC value. This confirms the good intracellular activity of macrolides and fluoroquinolones and the low intracellular activity of beta-lactams. PMID- 3325907 TI - [Alveolar macrophages and antibiotics. Review]. AB - Although alveolar macrophages play a key role in pulmonary defence against infections, little is known about interactions of these cells with antibiotics. In vitro, some drugs fail to enter alveolar macrophages readily; in contrast, other antimicrobial agents (clindamycin, erythromycin, ethambutol) are highly concentrated by these cells, as well as josamycin, erythromycin and spiramycin in vivo. Moreover, clindamycin, erythromycin, chloramphenicol, rifampin and pefloxacin lead to an increased phagocytosis by alveolar macrophages, either by compromising bacterial antiphagocytic components or stimulating proper phagocytic activity of the cell. The influence of antibiotics upon mechanisms of microorganisms destruction (production of oxygen metabolites, oxygen independent system), upon regulation of lymphocyte functions (interleukin 1, prostaglandin E2) or other secretory activities (enzymes, modulators of cell activities, various bioactive products) have not been extensively studied and require further investigations. PMID- 3325909 TI - [Effect of antibiotics on IL-1 in vitro production by human monocytes]. AB - The effects of penicillin, macrolides (spiramycin and erythromycin), cephalosporins (cefaclor and cefadroxil), cycline (doxycycline) and quinolones (pefloxacin, ciprofloxacin and ofloxacin) on extracellular and cell-associated interleukin-1 activity from human monocytes were investigated in vitro. When cells were treated with 10 micrograms/ml of quinolones, cephalosporins or penicillin, no effect on IL-1 production could be detected. Using 100 micrograms/ml, extracellular IL-1 activity was found to be decreased by quinolones (about 35% of the control without antibiotic) without modification of the cell-associated IL-1 activity. Extra and intracellular IL-1 was only slightly decreased by cephalosporins, while penicillin did not alter the IL-1 activities. Spiramycin and doxycycline using 100 micrograms/ml increased extracellular IL-1 while cell-associated was decreased. A toxic effect may have been exerted by these antimicrobial agents. PMID- 3325910 TI - [Quinolones and phagocytosis]. AB - Fluoroquinolones as pefloxacin (PEF), ciprofloxacin (CIP), ofloxacin (OFL), norfloxacin (NOR) and enoxacin (ENO), are able to interfere with phagocyte bacteria interaction. Active forms of PEF, CIP and OFL are concentrated in macrophages (MA) and polymorphonuclear leukocytes (PMN). These molecules appear to be free in MA cytoplasm and their release is rapid after withdrawal of extracellular antibiotic. Pretreatment of different species of bacteria (Enterobacteriaceae, S. aureus) with sub-CMIs of CIP and PEF, leads to morphologic modifications of bacteria and increases their engulfment by PMNs. Pretreatment of PMNs with therapeutic concentrations of PEF, NOR and ENO, but not CIP, increases phagocytic capacity and/or chemiluminescence. S. aureus pretreatment with sub-CMIs of CIP enhances intracellular killing. Adding of PEF after L. pneumophila phagocytosis by MA, involves a significant intracellular killing even after withdrawal of the extracellular drug. These different properties could explain good therapeutic results in severe infection treatment when the antibacterial activity of an antibiotic is not really sufficient to cure the infectious disease. PMID- 3325911 TI - [Effect of various antibiotics on granulopoiesis, in mice treated with cyclophosphamide, in an in vivo model of experimental C. albicans infection]. AB - The effect of piperacillin (PIP), cefotaxime (CTX), cefoxitin (CXT) on the natural resistance to C. albicans infection has been evaluated in vivo, in normal or neutropenic mice, in correlation with the PMN count in the peripheral blood. In neutropenic mice treated with PIP or CTX, the number of PNN increased more rapidly and higher than in CXT treated or control mice. A dose dependent increased resistance to infection was observed in PIP treated mice. It did not parallelled the PMN level found in different group of mice. The explanations might be a decrease of functional activity of PMN and/or an increase proliferation and differentiation of others effector cytotoxic cells. PMID- 3325912 TI - [Effect of antibiotics on T lymphocyte responses]. AB - T lymphocytes play a central role in the immune response. Coming from the bone marrow, they are attracted by the thymus where they are educated, they mature and differentiate into two main subsets: helper T-cells and suppressor/cytotoxicity T cells. T lymphocytes are involved in the immune response at different levels. As "conductor" of the whole lymphoid system, they are able to recognize foreign antigens and to induce the activation and the regulation of other T-cells and also B cells by the way of many soluble factors named lymphokines. As effector cells of cell-mediated immune responses, they are able to provoke delayed type hypersensitivity reactions and to specifically kill target cells (anti-viral cytotoxicity, for instance). The in vitro effect of some antibiotics on T-cells has been investigated. Clearly, a lot of them are able to modulate T-cell functions. PMID- 3325913 TI - Cellular requirements of IgE-antibody regulation. AB - Regulation of IgE antibody response is T-cell dependent. It has been suggested that IL-4 (BSF-1) induces the expression of Fc epsilon RII on B-lymphocytes. Soluble molecules of the FC epsilon RII with various molecular weights represent IgE-binding factors which according to the current opinion either enhance or suppress the IgE-antibody response. In mice IgE suppressive factors were obtained, which inhibited IgE-synthesis in vitro and in vivo. IgE suppressive factors were also obtained by incubating MLN-cells with monoclonal IgE. In humans IgE binding factors are present within serum of normal donors. In atopics IgE-BF is apparently complexed with IgE. Thus, it becomes clear that the expression of IgE-bearing lymphocytes as well as the secretion of IgE is cytokine mediated. PMID- 3325914 TI - [The role of IgE in recurrent ORL infections in children]. AB - The high incidence of bacterial super-infection in atopic individuals has long been known, especially in asthma and atopic dermatitis. In recurrent ENT infections in children, increased IgE levels are found in half the cases; this increase results from two main mechanisms: a predisposition to allergy (often with positive RASTs), and certain viral infections: respiratory syncytial virus, para-influenzae, and measles, that trigger production of partly non-specific serum IgEs. In the latter situation, the increased IgE levels are both a cause and a consequence of recurrent infections. More recently, in some forms of atopic dermatitis (infant and Buckley syndrome), attention has been drawn to the severity of viral superinfections (herpes, chickenpox, vaccine), which is directly correlated with the IgE levels. The mechanism of such infections is unclear: the local increase in IgE levels is responsible for degranulation of mastocytes which in turn results in edema, fissures of mucosae and congestion; an effect on the lymphocytic response is possible, with inhibition of the production of certain lymphokines, especially interleukins. PMID- 3325915 TI - [Beneficial effects of the combination of antibiotics and immunomodulating lipopeptides]. AB - Although antibiotics are efficient therapeutic weapons, their actions is limited in immunocompromised patients. The efficacy of immunomodulators which restore the immune system could be improved if they were associated to infra-active doses of antibiotics which prepare the bacteria to the immune system attack. Thus it seems possible to obtain a therapeutic gain with such an association and, consequently, to avoid the emergence of antibiotic-resistant germs. PMID- 3325916 TI - [Effect of cephalosporins on lymphocyte proliferation and immunoglobulin E production]. AB - We studied the effects of three cephalosporins (cefadroxil, cefaclor, cephalexin) on an in vitro model of human mononuclear cell proliferation in response to polyclonal mitogens. Cefadroxil, and to a lesser extent cefaclor and cephalexin, induced a decrease of proliferative responses to phytohaemagglutinin and concanavalin A. This decrease was not due to a direct effect on lymphocytes, but depended on the presence of adherent monocytes in the cultures. Cephalosporins stimulated the release of prostaglandins E2 by monocytes, generating a suppressive activity. Cefadroxil and cephalexin were in vivo given to Brown Norway rats sensitized to DNP-OVA to induce a primary and secondary IgE specific response. The administration of cefadroxil provoked a clear decrease of the secondary IgE response. As the IgE production closely depends on T suppressor cells, we hypothesize that cefadroxil could interfere with that production by stimulating a suppressor cell activity linked to an increased PGE2-release. PMID- 3325917 TI - Pavlov's conceptualization of unconditional reflexes, or instincts, within the framework of the theory of higher nervous activity. AB - According to I. P. Pavlov's theory of higher nervous activity, the establishment and dissolution of conditional reflexes enhances the higher organism's adaptation to the external environment. Pavlov asserted that, ontogenetically, conditional reflexes are based upon innate, unconditional reflexes (UR) or instincts. Pavlov did not distinguish between URs and instincts, but he preferred the former term. Phylogenetically the URs emerged out of well-established conditional reflexes during the development of higher organisms. An outgrowth of the experimental conditioning procedure, developed during the second decade of this century, was the observation and delineation of new URs. While studying human nervous and psychiatric disorders in the 1930s, Pavlov elucidated other URs. Pavlov identified 13 major URs, but he failed to formulate an exhaustive classification scheme of URs. PMID- 3325918 TI - Gantt, Pavlov and Freud: a comparison. AB - Contrasts between classical Pavlovianism and classical psychoanalysis have been emphasized, but there are also significant similarities of which I write. A recent edition of a textbook of psychiatry which is widely used in the United States (Kaplan and Sadock 1985) indexes neither Pavlov nor Gantt, although it provides extensive coverage of psychoanalysis. PMID- 3325919 TI - Horsley Gantt: through the camera eye. PMID- 3325920 TI - [A strategy for studying a mutation]. AB - In this short survey, the author analyzes the main principles and some of the methods used for the analysis, at the molecular level, of a mutation causing a monogenic disease. The recent advances in molecular biology techniques allow the identification of such a molecular lesion in the human genome. A molecular probe, i.e. an isolated fragment of DNA, is the main tool for such a purpose; it is necessary for recognizing, isolating and analyzing an abnormal gene. When no molecular probe is available or when the primary defect responsible for the disease is unknown (Duchenne muscular dystrophy, cystic fibrosis), the strategy of "reverse genetics" briefly exposed here is a breakthrough in the molecular genetics of hereditary diseases. PMID- 3325921 TI - [Keratosis follicularis decalvans: nosological discussion of Siemens' disease. Apropos of 3 cases]. AB - We describe 3 cases of keratosis follicularis decalvans (Siemens' disease): a 15 year old boy and a 7 year old boy and his father. They represent 2 different patterns of the disease with different clinical courses and genetic background: an autosomal dominant type of good prognosis with elevated argininemia and absence of follicular atrophy in both father and son, a sporadic type, clinically severe, with follicular atrophy. This raises the question of the nosology of the so-called Siemens' disease, since it includes actually different diseases of variable prognosis. PMID- 3325922 TI - [A migrating ear of barley: a curious story of an intrabronchial foreign body]. AB - A case of migrating inhaled ear of barley in a 2 1/2 year old boy is reported with: 1) mild initial symptoms at the time of inhalation followed by a symptomless interval of 8 days; 2) at day 9 fever and dyspnea, right paracardiac infiltrate with pleural reaction on X-rays, normal bronchoscopy; 3) at day 11 extensive right pneumothorax; 4) at day 20, right axillary inflammatory lesion; 5) at day 28 expulsion of an ear of barley from this lesion, followed by complete recovery. PMID- 3325923 TI - [Digestive cystic duplications: contribution of ultrasonography in the neonatal period. Apropos of 3 cases]. AB - Three cases of enteric duplication cysts in newborns are reported. The importance of the ultrasonographic exploration for the diagnosis is outlined. PMID- 3325924 TI - [High-frequency ventilation]. AB - The authors describe the methodology of high frequency ventilation in the newborn infant. Ventilation by oscillator (HFO) actually represents the best method for ventilation in newborn infants; the rate of ventilation is between 15 and 25 Hz/min. They report their experience of HFO use for the treatment of hyaline membrane disease in newborns. PMID- 3325925 TI - Family kinetic drawings as a screening instrument. PMID- 3325926 TI - Pharmacokinetics of the newer fluoroquinolones. AB - A large number of pharmacokinetic studies have been carried out using 4 quinolones in order to estimate total and renal clearance, to examine tissue penetration, to establish suitable dosage regimens and to determine the influence of kidney and liver impairment on the pharmacokinetic behaviour. Although the quinolones are poorly water soluble over the physiological pH range (6-8) they are well absorbed following oral administration. Ofloxacin is almost completely absorbed and ciprofloxacin has been shown to have an absolute bioavailability of 0.70. Plasma protein binding varies greatly from quinolone to quinolone ranging from about 10% in the case of norfloxacin to more than 90% in the case of nalidixic acid. Penetration of the quinolones into the prostate is generally good. Most quinolones, too, have been shown to penetrate blister fluid rapidly and this model has proved useful in distribution studies. Some quinolones, like ofloxacin, are excreted largely unchanged while others like pefloxacin and acrosoxacin, are almost completely metabolized. Conjugation to very water-soluble glucuronides is not common although other types of metabolites have been shown. Little information appears to have been published on the effect of liver disease on the metabolism of the quinolones. This must be an important consideration for this type of drugs which are subject to hepatic transformation. The pharmacokinetic behaviour of quinolones in patients with impaired renal function has been extensively studied. The interaction of food on the absorption does not seem to be great, there is however evidence of a drug interaction between theophylline and some of the newer quinolones. Sucralfate and antacids containing Mg2+ or (and) Al3+-ions can markedly impair the absorption of quinolone antibiotics. PMID- 3325927 TI - Comparative activities of five antimicrobial agents in experimental Proteus pyelonephritis in mice. AB - Five antimicrobial agents, ciprofloxacin, ticarcillin, piperacillin, aztreonam and gentamicin, were compared both in vitro (MIC's, time-kill studies) and in vivo, in the treatment of experimental Proteus mirabilis pyelonephritis in mice. In the treatment of the pyelonephritis, ciprofloxacin was clearly superior to the other agents, both with respect to the percentage of sterile kidneys after treatment as with respect to the mean numbers of bacteria per kidney. The results can only be partially explained by the in vitro activities of the different antibiotics. PMID- 3325928 TI - Influence of dose frequency on the therapeutic efficacies of ciprofloxacin and ceftazidime in experimental Klebsiella pneumoniae pneumonia and septicemia in relation to their bactericidal activities in vitro. AB - The antibacterial activities of ciprofloxacin versus ceftazidime against Klebsiella pneumoniae in vitro and in vivo were compared. Although there was only a minor difference in MBC values between both drugs ciprofloxacin demonstrated a high and dose-dependent bacterial killing rate in vitro and in lungs of leukopenic rats in contrast to the more time-dependent bactericidal activity of ceftazidime. After treatment of a K.pneumoniae pneumonia and septicemia the efficacy of ciprofloxacin was only slightly influenced by the mode of administration, either at 6-h intervals or continuously, whereas ceftazidime was far more effective after continuous administration. This resulted in a superior efficacy of ciprofloxacin after intermittent treatment as compared to ceftazidime, whereas ceftazidime was more effective after continuous administration as compared to ciprofloxacin. Also ciprofloxacin proved to be bactericidal against bacteria that were not actively growing, both in vitro and in vivo, whereas ceftazidime was not. PMID- 3325929 TI - Ciprofloxacin for infection prevention in patients with acute leukemia. AB - Ciprofloxacin, a new quinolone derivative, was given prophylactically (500 mg twice daily) to 15 patients with acute leukemia during remission induction treatment. The effect on the microbial flora of the alimentary tract was evaluated. A rapid elimination of Enterobacteriaceae was observed. Bacteriodes and Clostridium species were not affected. Few ciprofloxacin resistant strains were isolated but did not lead to colonization. In a randomized study 56 patients with acute leukemia received either ciprofloxacin or trimethoprim sulfamethoxazole plus colistin for prevention of infections. Six major infections occurred in 28 patients receiving ciprofloxacin, and 11 major infections in 28 patients receiving trimethoprim-sulfamethoxazole plus colistin. No infections caused by Gram-negative bacilli were seen in the ciprofloxacin group compared to 17 in the other group (p less than 0.02). Ciprofloxacin prevented colonization with resistant Gram-negative bacilli while 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole (p less than 0.01). Ciprofloxacin was better tolerated than trimethoprim-sulfamethoxazole + colistin; fewer side effects occurred. PMID- 3325930 TI - Treatment of respiratory tract infections with pefloxacin in critically ill patients hospitalized in a surgical intensive care unit. AB - Respiratory tract infections were treated with pefloxacin in fifteen patients, who were hospitalized in the intensive care unit and required artificial ventilation. The treatment was successful in ten patients. Development of resistance was observed in Staphylococcus aureus (two times) and Pseudomonas aeruginosa (four times). No adverse reactions were seen. PMID- 3325931 TI - Ciprofloxacin for respiratory tract infection with Pseudomonas aeruginosa. AB - Thirty one patients were treated with oral ciprofloxacin for bronchitis with Pseudomonas aeruginosa. Twenty eight patients had permanent and 14 transient risk factors. Nine patients had a hospital infection with Pseudomonas aeruginosa. Sixteen patients were cured, complete or partial, but Pseudomonas aeruginosa persisted or recurred in 19 patients. Patients with hospital infection did better than other patients. There was a significant decrease in in vitro susceptibility of persisting strains of Pseudomonas aeruginosa to ciprofloxacin and a tendency of recovery of susceptibility for the drug after treatment. PMID- 3325932 TI - Treatment of multi-resistant urinary tract infections in patients with multiple sclerosis. AB - Multi-resistant nosocomial urinary tract infections occurring in thirty patients with neurogenic bladder dysfunction were treated with ciprofloxacin 100 mg twice daily Early bacteriological eradication was obtained in 48.3%, persistence in 34.5% and superinfection in 17.2%. Recurrence, 30 days after initial eradication occurred in 50% while late eradication was maintained in 35% and reinfection with another germ was noted in 15%. Most recurring and reinfecting germs were still susceptible to ciprofloxacin. The drug was well tolerated. The overall outcome was mainly determined by the vesico-urethral dysfunction itself and by the presence of indwelling bladder catheters. PMID- 3325933 TI - Treatment of chronic bacterial prostatitis with ciprofloxacin. AB - Thirty two patients with proven chronic bacterial prostatitis were treated with ciprofloxacin 500 mg twice daily orally for four weeks. The causative organisms, cultured from prostatic fluid were Enterobacteriaceae (19 patients), enterococci (9), staphylococci (4), streptococci (3), non-fermentative Gram-negative rods (2) and anaerobic bacteria (9). Nineteen patients had pure cultures, 13 mixed cultures. The susceptibility of all organisms to ciprofloxacin, sulfamethoxazole, trimethoprim and doxycyclin was determined by agar dilution. The effect of therapy was measured by clinical parameters and by repeated cultures of prostatic fluid during and after therapy up to six months. Clinical cure (at one month after therapy) was obtained in 22 patients, improvement in seven; two patients did not respond, one patient had to stop during therapy because of severe nausea. No other side effects were noted. Ciprofloxacin may be a useful alternative drug in the treatment of prostatitis. PMID- 3325934 TI - Quinolones in the treatment of gonorrhoea and Chlamydia trachomatis infections. AB - The results of two therapeutic trials in female patients with uncomplicated urogenital gonorrhoea (A) and in male patients with uncomplicated urethral gonorrhoea (B) treated with either 200 mg and 400 mg enoxacin orally, of one therapeutic trial in male patients with uncomplicated urogenital gonorrhoea treated with either 250 mg or 500 mg ciprofloxacin orally (C) and of one therapeutic trial in male patients with non-gonococcal urethritis (NGU) treated with ciprofloxacin 1 g daily during seven days (D) are presented and compared with the results of other investigators. The cure rate in study A was 100% (n = 40) in the 400 mg group and 95.7% (n = 46) in the 200 mg group. The cure rate in study B was 92% (n = 78) in the 400 mg group and 90% (n = 77) in the 200 mg group. In both studies no antichlamydial effect of enoxacin was observed. The cure rates in study C were 100% with 250 and 500 mg. An antichlamydial effect seemed to be present. In studies A, B and C side effects were minor and rare and were mainly nausea and headache. In study D (100 patients suffering from NGU) disappearance of Chlamydia trachomatis and Ureaplasma urealyticum one day after the end of treatment was observed in 29 of 32 (91%) and 28 of 32 (88%) cases, respectively. Pyuria disappeared in 44% and 74% of the patients showed clinical cure. However, two weeks after the end of treatment Chlamydia trachomatis and Ureaplasma urealyticum were observed in respectively six and eight cases. In 30% pyuria was still absent. Side effects were only minor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3325935 TI - The use of fluoroquinolones in chronic otitis suppurativa. AB - The present review covers fluoroquinolone usage in chronic otitis suppurativa (COS) in case of chronic otitis media, cholesteatoma, radical mastoid cavity infection and chronic or relapsing otitis externa. A total of six publications were included in the final evaluation. Enoxacin was effective in 35%; ciprofloxacin (five publications) was used in 82 patients with 67% effectivity in otitis externa and otitis media and 61% effectivity in radical mastoid cavity infection. No serious adverse reactions were reported. The promising efficacy of otitis media and otitis externa and safety profile needs further confirmation in double blind prospective clinical studies, that will provide a firm basis for changing the current treatment schedules of COS. PMID- 3325936 TI - Treatment of chronic postsurgical osteomyelitis with ciprofloxacin. AB - Sixteen patients (11F, 5M, age 18-83, mean 59.8 years) with chronic postsurgical osteomyelitis were treated with ciprofloxacin. The dosage was 500 or 750 mg twice daily orally during one to six months; four patients started with 300 mg twice daily intravenously and changed after 3-7 days to oral therapy. Twelve patients had implanted prostheses. The organisms involved were Enterobacteriaceae (11), Pseudomonas aeruginosa (7), Staphylococcus aureus (5), Streptococcus faecalis (4) and Bacteroides fragilis (1). Nine patients had pure cultures, seven mixed cultures. Cure (disappearance of infection symptoms, return of normal function with negative cultures, without resurgery) was obtained in 11 patients, improvement (resurgery required to obtain complete cure) in two. Three patients with infections by Staphylococcus aureus (2) and Pseudomonas aeruginosa (1) failed to respond after one and four months treatment respectively. No side effects were observed. PMID- 3325937 TI - Is there a dichotomy between the clinician and the pathologist in hematology? PMID- 3325938 TI - [Basophil leukemia, development of a chronic myeloid leukemia. Apropos of a case and review of the literature]. AB - Basophilic leukemia is a rare disease accounting for less than 2% of all hematopoietic malignancies and little is known about the best therapeutical approach. We report a case of basophilic leukemia occurring as an accelerated phase of chronic myelogenic leukemia in a 50 year old man with a past history of uranium and thorium exposure. He was successfully treated with intensive chemotherapy and total body irradiation followed by autologous peripheral stem cell transplantation. Such an approach has never been reported in this disease. However, the benefit on survival could not be evaluated because of a fatal opportunistic infection. The cases of basophilic leukemia reported in the literature are discussed. PMID- 3325939 TI - [Myeloid differentiation antigens: characterization and expression in acute myeloblastic leukemias]. AB - We report the main characteristics of myeloid clusters of differentiation, recently described and confirmed at the 3rd International Workshop on Human Leukocyte Differentiation Antigens (Oxford, September 1986). The principal studies concerning immunopheno-typing of acute myeloblastic leukemias, its concordance with the FAB classification, and its prognostic implications are analysed. PMID- 3325940 TI - Quantitative evaluation of myocardial stress/rest 201TL SPECT: results of a ROI based method in 108 patients with CHD. AB - ROI-based polar maps (33 ROIs) were employed to evaluate quantitatively stress/rest myocardial 201Tl SPECT in 108 patients with angiographically proven coronary heart disease (CHD) in comparison with 30 controls. Sensitivity in detecting a CHD with stenoses of greater than 50% of luminal diameter was determined versus normal regional values (+/- 2.5 SD) employing vitality (VI) and wash-out corrected redistribution (RD). The method was evaluated referring to the severity of the disease, to the number of ROIs displaying changes [(a) 1 ROI, (b) greater than 2 ROIs], to validity of VI, RD or a combination thereof, and for specificity. Wash-out values were found to depend on degree of stress individually achieved and thus were not used as a threshold criterion. Sensitivity in supply areas with old myocardial infarctions was 95% (a) and 86% (b), resp. With no infarction, it was 96% (a) and 79% (b), resp. VI in stenosis greater than 75% was more sensitive than RD. However, combined evaluation of VI and RD yielded sensitivities from 91-100% (a) and 77-94% (b), resp. for different main supply areas. In stenosis less than 50% with normal VI, RD was positive in 18-31%. Specificity turned out to be 91% (a) and 97% (b), resp. We conclude that the method presented is reliable to quantify numerically 201Tl kinetics in myocardial SPECT, aimed at detecting and describing CHD. PMID- 3325941 TI - [Malignant melanoma: the present state of knowledge and research]. PMID- 3325942 TI - [Chronic respiratory insufficiency, its pathophysiology and treatment]. PMID- 3325943 TI - [Effect of betamethasone on the lipid composition of pulmonary surfactant, ependymal cells and lung tissue after surgical procedures on the thorax of dogs]. AB - The lipid composition of pulmonary surfactant, ependymal cells and pulmonary tissue after surgery on the thorax in dogs was determined. 24 hrs after removal of one lung, in the other one there occurred changes in the quantity of respective classes of phospholipids of the pulmonary surfactant, manifesting themselves by a considerable drop in the amount of phosphatidylcholine (by 25%), phosphatidylethylamine (by 47%), phosphatidylglycerol (by 98%) and phosphatidylcholine: sphingomyelin ratio (by 63%), as well as by a rise in the amount of lysophosphatidylcholine (by 83%), phosphatidylserine (by 54%) and sphingomyelin (by 25%). In dogs receiving betamethasone in the post-operative period the changes were less intense: the amount of phosphatidylcholine decreased by 15%, phosphatidylethanolamine by 29%, phosphatidylglycerol by 94% and phosphatidylcholine: sphingomyelin ratio by 63%. The amount of lysophosphatidylcholine increased by 26.7%, phosphatidylserine by 29.1% and sphingomyelin by 22.2%. Similar changes were observed in the phospholipids of lining cells, while changes in the composition of phospholipids of pulmonary tissue in most cases appeared insignificant. Insignificant, too, were changes in the composition of neutral lipids of the tissular fractions examined. The described changes in dogs not receiving betamethasone correspond to those found in man in the course of acute respiratory insufficiency syndrome. Betamethasone was found to exert a protective effect on the phospholipids of pulmonary surfactant, soothing the biochemical changes brought about by surgical removal of one lung. PMID- 3325944 TI - [Studies of the mechanism of bacterial inactivation after administration of the preparation Polchlor K]. AB - The purpose of the study was to determine the effect of chloroiodic complex compound with non-ionic surface active substances such as Polchlor K on the kinetics of dying, activity of bacterial dehydrogenases and glucosidases as well as ultrastructure of bacterial cells on the example of Escherichia coli and Staphylococcus aureus. The evaluation of the kinetics of bacteria dying under the preparation activity revealed higher activity against E. coli than S. aureus. It was found that the preparation in bactericidal concentrations decreased significantly dehydrogenase activity in the examined microorganisms and also affects the changes in their ultrastructure. The cell dying was mainly due to structure-functional lesions in the cytoplasmic membrane--initially inactivation of respiratory enzymes localized inside the cytoplasmic membrane and furthermore its structural lesion. PMID- 3325946 TI - [Effect of diseases of the digestive system on vitamin D and calcium metabolism]. PMID- 3325945 TI - [Remote results of the treatment of perforated peptic ulcer using sutures]. PMID- 3325947 TI - [Successful treatment by plasmapheresis of progressive edematous-infiltrative ophthalmopathy after corticotherapy failure]. PMID- 3325949 TI - [Current problems in injuries of the spine and spinal cord]. PMID- 3325948 TI - [Use of plasmapheresis in diseases of the nervous system]. PMID- 3325950 TI - Prognostic factors in borderline and invasive ovarian tumors of the common epithelial type. AB - Present reports show that surgical factors, response to therapy and histological criteria are important for predicting the prognosis of patients with common epithelial types of ovarian tumors. Newer techniques such as morphometry, DNA cytometry, immunological and immunopathological techniques may help to define prognostic factors even more accurately. As a result, these recently developed methods may enhance the value of well-established classical predictors of the outcome in case of borderline or invasive ovarian tumour. PMID- 3325951 TI - What's new in oncogenes and growth factors? PMID- 3325952 TI - Antipyretic activity of copper salicylate. AB - Thermal responses to copper II salicylate (200 mg/kg iv) were investigated in febrile rabbits (treated with E. coli lipopolysaccharide) at 3 ambient temperatures (Ta) of 5, 20, 28 degrees C. The compound produced antipyresis, which unlike that induced by sodium salicylate (200 mg/kg iv), increased with the drop of Ta. This antipyretic activity was accompanied by enhanced heat elimination which became most evident in thermoneutral conditions. The metabolic rate was intensified after treatment with both compounds. Possible mechanisms responsible for copper salicylate antipyresis are discussed. PMID- 3325954 TI - Current management of low-grade astrocytomas of childhood. AB - Astrocytomas are the most frequently encountered brain neoplasms in the pediatric age group. Current management strategies consist of surgery, radiation therapy, chemotherapy and immunotherapy, although the optimal treatment is yet to be defined. It is hoped that new treatment modalities, and reassessment of current regimens will improve outcome, better in terms of survival and quality of life. PMID- 3325955 TI - [Characteristics of cellular receptors for immunoglobulin fragments Fc]. PMID- 3325953 TI - Neurosonographic and biochemical correlates of periventricular leukomalacia in low-birth-weight infants. AB - The incidence of periventricular leukomalacia (PVL) was investigated by ultrasound in a group of 119 consecutively scanned low-birth-weight infants during a period of 3 years. The overall incidence of PVL was 6.7% while the incidence of peri-intraventricular hemorrhage was 44.5%. Ultrasound evidence of posthemorrhagic lesions was seen early and related strongly to follow-up findings. Evidence of cystic degeneration appeared later. The presence of PVL was confirmed by computed tomography at 5 months of age and anticipated by serial measurements of creatine kinase brain isoenzyme performed in the first 60 h of life. A significant correlation was observed between neurosonographic findings of PVL and high cord blood values of enzymatic pattern (p less than 0.02). Both were correlated with poor neurodevelopmental outcome at 12 months corrected age. PMID- 3325956 TI - [Determining the role of granulopoiesis (CSF)in the pathogenesis of human leukemia]. PMID- 3325957 TI - [Epidemiology of leukemia. I. Descriptive statistics]. PMID- 3325958 TI - [Metabolism of collagen in the process of liver fibrosis]. PMID- 3325959 TI - [Phenol]. PMID- 3325960 TI - Biological studies in human exposure to and poisoning with organic solvents. With special reference to kinetics, haematology, and serum chemistry. PMID- 3325961 TI - [Therapy of the sleep apnea syndrome]. PMID- 3325962 TI - [Nasal continuous positive airway pressure (nCPAP) therapy--practical experiences in 54 patients]. PMID- 3325963 TI - [Therapy of sleep apnea with an evening dose of retard theophylline (Euphylong)]. PMID- 3325965 TI - [Nocturnal home ventilation in patients with chronic respiratory failure caused by thoracic deformity and neuromuscular weakness]. PMID- 3325964 TI - [Therapy of nocturnal bronchial asthma: comparison of various doses of retard theophylline]. PMID- 3325966 TI - [Pulmonary and respiratory syndromes. 2]. PMID- 3325967 TI - Improved purification and some molecular and kinetic properties of sn-glycerol-3 phosphate dehydrogenase from Saccharomyces cerevisiae. AB - The purification procedure for isolating sn-glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) from Saccharomyces cerevisiae was improved by the introduction of an ion-exchange step. Enzyme yields were doubled and the specific activity was increased as compared to the original procedure. A new value of 42,000 was obtained for the molecular weight by several denaturing methods. By native gel chromatography the molecular weight appears to be 31,000 as reported earlier. Michaelis constants were found to be 0.37 mM with dihydroxyacetone phosphate as the variable substrate and 0.018 mM for NADH as the variable substrate. PMID- 3325968 TI - Control of placental glucose transfer. AB - There is little evidence to suggest that the membrane transfer mechanism of the placenta for glucose becomes saturated until maternal blood glucose concentrations are quite high. Also, recent evidence suggests that the membrane transport system for glucose in the placenta is not stimulated by maternal or fetal insulin. Furthermore, there is no solid evidence that hormonal or non hormonal factors function in vivo to limit membrane transport of glucose in the placenta. Therefore, the limited data which are available suggest that there are no specific mechanisms which acutely regulate placental membrane transport of glucose, and that this membrane transport mechanism operates to maximize maternal to-fetal glucose transfer. The rate of maternal-to-fetal glucose transfer is a function of the transplacental concentration gradient. This gradient appears to be under the control of fetal insulin and placental lactogen. The available data suggest that both hormones act to increase this concentration gradient: insulin by decreasing fetal blood glucose, and placental lactogen by both decreasing fetal and increasing maternal blood glucose concentrations. Furthermore, high rates of glucose uptake by fetal erythrocytes tend to promote maintenance of this concentration gradient. Therefore, these influences of the maternal-fetal concentration gradient promote transplacental glucose flux to the fetus. As illustrated by the fetal complications associated with maternal hyperglycaemia, the cellular and organismic physiology of the fetus and placenta appears to maximize, rather than optimize, glucose availability to the fetus. It may be, however, that during normal pregnancy, maximal availability is optimal for fetal development. PMID- 3325969 TI - Direct chromosomal preparation for studying hydatidiform moles. AB - This report describes a simple direct method to obtain chromosomes from hydatidiform moles. Of 24 moles, 20 have been successfully karyotyped by this method. Of the 20 cases, 14 were complete and six were partial. The karyotype of complete moles was invariably diploid. Three of the partial moles were triploid (69,XXX), but three showed diploid/tetraploid mosaicism. PMID- 3325970 TI - [70th anniversary of the Great October Socialist Revolution]. PMID- 3325971 TI - [Insulin therapy and its complications]. PMID- 3325972 TI - [A histofluorimetric method of evaluating the insulin level of pancreatic islets]. AB - Up to now results of the histochemical luminiscent reaction to insulin in pancreatic islet beta cells (the pseudoisocyanin test) were assessed by a visual method which permitted establishing the difference only in substantial variations of fluorescence intensity. The authors employed a quantitative method for assessment of the results of the test using a microfluorimetric attachment designed by them. They also provided data on the measurement of the insulin content in pancreatic islet beta cells of rats in different experimental exposures using this method. PMID- 3325973 TI - [Autoimmune aspects of insulin-dependent diabetes mellitus. Humoral immunity]. PMID- 3325975 TI - [The systems approach in space biology and medicine]. PMID- 3325974 TI - [Diabetic angiopathies of the legs (clinical aspects, diagnosis and treatment)]. PMID- 3325976 TI - [Status of the anti-tuberculosis activities in the USSR and the objectives with regard to their further improvement]. PMID- 3325977 TI - [Proteinases of alveolar macrophages and the liquid phase of bronchoalveolar washings in guinea pigs during the development of experimental tuberculosis]. PMID- 3325978 TI - [Therapeutic properties of sodium succinate in pulmonary tuberculosis]. PMID- 3325979 TI - Effect of phorbol-12-myristate-13-acetate (PMA) on the fine structure of Trypanosoma cruzi and its interaction with activated and resident macrophages. AB - Epimastigotes of Trypanosoma cruzi showed many filopodium-like projections from the flagellar membrane when incubated in the presence of 100 ng/ml (a concentration which does not interfere with cell motility and viability) phorbol 12-myristate-13-acetate (PMA). PMA is a substance which binds to the membrane associated protein kinase C. Few of these projections were observed in control parasites. PMA, when added to the interaction medium, significantly increased the attachment of epimastigotes to the surface and their ingestion by resident or activated mouse peritoneal macrophages maintained in vitro. PMA, however, did not interfere with the ingestion of trypomastigotes. PMID- 3325980 TI - Plasmodium berghei malaria: effect of acute phase serum on immunity generated in rats by infection and by vaccination. AB - Acute phase serum (APS) given at the time of challenge with Plasmodium berghei inhibited the generation to immunity to the infecting plasmodia. Administered with a single dose of vaccine, it inhibited induction of immunity by the vaccine. Three weekly doses, the last given two weeks before infection, induced immunity. Administration of vaccine simultaneously with infection neither aggravated nor ameliorated the infection. These results indicate that the effect of administration of APS on immunity generated by immunization or infection is dose- and time-dependent. The depression of immunity induced by this serum is thus temporary, the host finally overcoming the depression and responding to the plasmodial antigen in the serum. The interaction of vaccine and infection observed indicates that the introduction of vaccine is not detrimental to the individual incubating infection; rather, the vaccine is rendered useless, the reducing the aggregate benefit of the immunization to the group. PMID- 3325982 TI - Islet morphology in young, genetically diabetic Chinese hamsters during the hyperinsulinemic phase. AB - Plasma glucose and insulin levels were measured in genetically diabetic (subline L) hamsters from 2 1/2 weeks to over 1 year of age. This nonobese subline is known for subnormal pancreatic insulin release. Hyperglycemia was seen from 4 weeks onward. A short period of hyperinsulinemia was seen at 6 weeks of age, after which plasma insulin levels were not different from normal. During the hyperinsulinemia phase (age 6 weeks), pancreatic insulin content was subnormal, islet volume (as percent of pancreas cross-sectional area) and islet size (as islet cross-sectional area in micron2) were not different from normal, islet morphology appeared normal in electron micrographs, but granule volume was slightly but significantly below normal. Because the islets appeared morphologically normal, except for the slight degranulation during the hyperinsulinemic phase, these data suggest (a) that the islets "hypersecrete" to reduce hyperglycemia; but (b) synthesis does not increase enough to maintain a normal pancreatic insulin content; (c) that the first sign of pancreatic failure may be degranulation and decreased insulin synthesis or content; (d) that early peripheral resistance to insulin, rather than early islet failure, may cause the early hyperglycemia, and (e) that early hyperglycemia or insulin resistance contributes to the later islet exhaustion, which is seen in these diabetic animals when adult. PMID- 3325981 TI - Bovine babesiosis: induction of protective immunity with culture-derived Babesia bovis and Babesia bigemina immunogens. AB - The comparative protective efficacy of culture-derived Babesia bovis and B. bigemina immunogens against challenge exposure of susceptible crossbred cattle to heterologous strains was examined and correlated with the antigenic threshold requirements for induction of protective immunity. Strong protection was observed in animals vaccinated with 10 ml-equivalent doses of soluble, B. bovis exoantigen containing supernatant fluids. Similar protective responses to B. bigemina exoantigens were evident even at 1 ml-equivalent dosages. In addition, the efficacy of a combined B. bovis-B. bigemina immunogen was assessed with a dose response analysis in highly susceptible, purebred cattle. Vaccinated animals were protected against clinical babesiosis, and significant weight gains were recorded after challenge infection with virulent parasites. PMID- 3325983 TI - Rat fetal islets as a useful model for the study of insulin release failure. AB - To study the mechanism of imparied insulin secretion from rat fetal islets, the insulin responsiveness of islets from fetuses (day 21.5 of gestation) to a variety of secretagogues was compared with that of adult rat islets. Forskolin (30 microM)-induced insulin release from fetal and adult islets was 2.7-and 2.5 fold higher, respectively, than that from islets treated with 5.6 mM glucose alone. The effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (200 nM) were also similar in fetal and adult islets. Thus, the responsiveness to forskolin and TPA showed no significant difference in adult and fetal islets. A synergistic effect of combinations of various insulin secretagogues was observed in adult islets; however, a weak synergistic effect was present with gliclazide plus TPA only in fetal islets. After islets were cultured in RPMI 1640 (containing 11.1 mM glucose), gliclazide-, forskolin-, and TPA-induced insulin release reached the levels obtained in adult islets. However, the synergistic effect of gliclazide and TPA disappeared after culture of the islets. These results suggest that the poor insulin secretion from fetal islets is not due to a defect in the activating system of either cAMP or C-kinase, but to the immaturity of the interaction of those messenger systems. PMID- 3325984 TI - Anomeric specificity of the insulin and glucagon secretory responses to D-glucose in lean and obese Zucker rats. AB - The perfused pancreas of lean and obese Zucker rats was exposed, in the presence of L-leucine, to the anomers of D-glucose, which were administered on four successive occasions in the alpha/beta/alpha/beta or beta/alpha/beta/alpha sequence. In 5 lean and 6 obese rats, alpha-D-glucose was more efficient than beta-D-glucose in both stimulating insulin secretion and suppressing glucagon release. Although D-glucose evoked a greater release of insulin and, during prolonged exposure to the hexose, a less pronounced suppression of glucagon secretion in obese than lean rats, the anomeric specificity of these secretory responses was not different in the two groups of animals. In one lean rat, however, alpha-D-glucose, while efficiently stimulating insulin release, failed on two occasions to inhibit glucagon secretion. This isolated observation raises the possibility that the anomeric specificity of functional events evoked by D glucose in the endocrine pancreas may occasionally be perturbed. PMID- 3325985 TI - Exocrine pancreatic function in dogs with denervated pancreas. AB - There is strong evidence that the vagus nerve plays an important role in exocrine pancreatic secretion. In the present study we examined the effect of total extrinsic denervation of the pancreas on exocrine pancreatic secretion to different stimuli in dogs. In the experiments we used the model of the orthotopic autotransplanted dog pancreas as described by Debas et al. Denervation of the gland did not significantly alter water and bicarbonate response to secretin. The dose-response curve of caerulein showed the denervated pancreas as sensitive as the intact gland. However, autotransplantation of the pancreas caused a significant decrease (p less than 0.05) in protein secretion during intraintestinal L-tryptophan in increasing doses. Furthermore, bicarbonate and protein secretion after food intake was significantly decreased in the denervated pancreas (protein: peak levels 380 mg/15 min and 135 mg/15 min; bicarbonate: 3.2 mEq/15 min and 1.4 mEq/15 min) (p less than 0.02). From our data we conclude that the denervated pancreas is as sensitive as the intact pancreas to stimulation by exogenous secretin and caerulein, whereas denervation of the pancreas causes an important influence in the intestinal phase of pancreatic secretion. PMID- 3325986 TI - [The role of bile and biliary salts in drug absorption]. PMID- 3325987 TI - [Zeta potential--fundamentals, measurement methods and application to pharmacy]. PMID- 3325988 TI - Development of progesterone antagonists as fertility regulating agents. PMID- 3325990 TI - Effect of age on the induction of in vitro drug metabolism by pregnenolone-16 alpha-carbonitrile (PCN); effect of age and PCN on immune responses. AB - The drug metabolizing capacity and the immune responses of normal and PCN treated young, adult and old rats were studied. In normal young and old rats the drug metabolism in general and the immune responses were reduced in comparison to adult animals. PCN treatment caused significant increase of drug metabolism in all age groups of animals due to induction of the microsomal enzymes of the liver. However, there were certain drug dependant variations in the different age groups of rats. PCN given in vivo affected differently the responses of T and B cells in the young, adult and old animals. PCN is a non-hormonal microsomal enzyme inducer and the question a-rises as to whether there is any connection between this process and the immune system. PMID- 3325989 TI - Preparation and properties of GnRH-loaded multilamellar liposomes. AB - Binding of the decapeptide gonadotropin releasing hormone (GnRH) to multilamellar liposomes was investigated with variation of the lipid matrix and of the medium conditions. It is demonstrated, that binding capacity of liposomes may be varied within wide limits if negatively charged phosphatidic acid is made a constituent part of the liposomes. Binding to liposomes is protecting GnRH against enzymatic hydrolysis by proteases, if structural integrity of liposomes is maintained. These properties are in favour of the application of liposomes as a drug carrier system for GnRH. The determination of the binding capacity and of the association constant for a definite system GnRH/lipid and, additionally, comparison of these data with analogous results concerning substance P [Pharmazie 39, 765 (1984)] furnish some new information with respect to the interaction of oppositely charged peptides and lipids. PMID- 3325991 TI - Pharmacokinetics of gonadotropin-releasing hormone and stimulation of luteinizing hormone secretion after single dose administration of GnRH incorporated into liposomes. AB - The properties of liposomes as a carrier for sustained release of gonadotropin releasing hormone (GnRH) was investigated. A mixture of egg phosphatidylcholine/egg-phosphatidic acid, binding GnRH with high capacity, was used for preparation of GnRH-carrier liposomes, which were of the multilamellar type in most experiments. As test animals we used rabbits and pigs, the last mentioned for checking the LH4 response to GnRH-injections, which was via the i.m. route throughout in this investigation. By measuring the kinetics of removal of GnRH from the injection site and by following the GnRH invasion into the circulation, it was demonstrated that GnRH release from liposomal depots is strongly slowed down, compared with injections of the free hormone. Further, plasma levels of GnRH were detectable up to 8 h generally, sometimes up to 20 h after injection. However, a considerable portion of GnRH bound to multilamellar liposomes was released so slowly in our case, that the concentration decreased even below the RIA detection limit. This appears clearly from our kinetic data. For this reason the resorption of GnRH from liposomes seems to be less efficient than after i.m. injections of the free hormone. With pigs also the LH response to the injection of GnRH-liposomes was relatively poor. Apparently, biological activity is missing with very low GnRH concentrations. The results furnish good information on how to modify the liposome carrier in order to produce preparations with changed rates of GnRH release. PMID- 3325992 TI - [Scheele as a pharmacist]. PMID- 3325994 TI - [Pharmaceutical education and scientific life in Berlin--then and now]. PMID- 3325993 TI - [Biochemical basis of pharmaceutical chemistry. 2. Chemotherapeutics]. PMID- 3325995 TI - [Berlin pharmacies over time]. PMID- 3325996 TI - [The development of the pharmaceutical industry in Berlin]. PMID- 3325997 TI - [Development of the nationally owned pharmaceutical wholesaler in Berlin]. PMID- 3325998 TI - Merocyanine 540. PMID- 3325999 TI - The effects of the ultraviolet wavelengths of radiation present in sunlight on human cells in vitro. PMID- 3326000 TI - Ocular photosensitization. PMID- 3326001 TI - Photodamage to the eye. PMID- 3326002 TI - Mandibular reconstruction using vascularized iliac bone grafts. PMID- 3326004 TI - Psychoanalytic aspects of obsessive compulsive disorders: some aspects of anal object relationships on the characterological features of control and possession. PMID- 3326003 TI - The use of psychopharmacology in obsessive compulsive disorders. PMID- 3326005 TI - Obsessive compulsive phenomena in adult obsessionality, compulsive personality disorder and obsessive compulsive disorder (neurosis). PMID- 3326006 TI - Research perspectives in obsessive compulsive disorders. PMID- 3326007 TI - Behavioral approaches to obsessive compulsive disorders: theoretical and clinical issues. PMID- 3326008 TI - Obsessive compulsive disorder in children. PMID- 3326009 TI - Characterization of the affective diathesis as it relates to bulimia. PMID- 3326010 TI - Validation of the Middlesex Hospital Questionnaire as a self-rating screening instrument for clinically significant psychological distress. PMID- 3326011 TI - Involuntary self-intoxication with triazolam. PMID- 3326012 TI - Catatonic stupor: unusual manifestation of temporal lobe epilepsy. PMID- 3326013 TI - Breaking with tradition: medication and psychotherapy. PMID- 3326014 TI - Management, administration, leadership: what's in a name? AB - In summary, I have argued that while research and publications in the field have tended to deal with management and administration--examining issues as if they were predominately structural, organizational and authority-oriented, the area that cries out for further attention is that of leadership. For, while managers can do, and administrators oversee--it is only leaders who can move us ahead. The field is in for a turbulent, difficult, but I suspect, exhilarating next new years. Our work is truly very different from that in most businesses--and while good "managers" may make money for business enterprises, for us, leadership is the critical ingredient. (I'm not even so sure that despite some experts disclaimer of the lack of importance of leadership in business, a closer look would not inevitably reveal a Kroc, Hewlett, DiLorenzo or Iacocca behind every successful corporate initiative anyway). With that in mind, we should increase both our study of the development of leaders and our attention to their development. To do less is to increase our difficulties, court further new disasters, and have even less control over our work and our future. We deserve and can achieve a better destiny. PMID- 3326015 TI - Cumulative index of Volumes 1-15 (1971-1985). PMID- 3326017 TI - Determining psychosis in retarded adults through psychological tests. PMID- 3326016 TI - Arthur Wigan and The Duality of the Mind. AB - It is not easy to see a simple outline in the progress of the idea of duality, because it did not develop evenly or reach the stage of general acceptance. From the seventeenth century there were shifts in some of the basic assumptions about how the brain and mind functioned, and there are some useful markers along the way to an era of more systematic studies. Descartes is the most convenient base. He had earlier firmly separated mind and matter in his philosophy, and is still chiefly known for that. But at the end of his life (1649) he tried to reconcile them by the device of a specific 'seat of the soul' in the brain through which information passed between brain and mind. Symmetry of the operation of the hemispheres was assumed. This theory had currency into the eighteenth century. At the end of that century Franz Gall of Austria and France was assigning discrete faculties to numerous parts of the brain on no strong evidence, and nothing the double form of the brain, without claiming independent action of the hemispheres. Hewett Watson in 1836 discussed duality more directly than had been the case before, and Arthur Wigan in 1844 asserted the duality of the mind roundly and treated the two hemispheres, not consistently, as two independent brains. He was not satisfied with independence, however, and tried various ways of allowing for joint action by the two sides of the brain, as well as for substitution, with one side having the power to act on behalf of both in cases of disease or injury. He also considered that one hemisphere, usually the left, was generally dominant; but he did not see the two hemispheres as differently constituted. Recognition of differentiation of function between the two sides came chiefly out of the largely French discussions, in the 1820s and after, about the location--frontal or not- of 'language', and out of the work and arguments of the middle of the century. Broca's left frontal language centre became widely known, though its experimental base was weak and he himself seems to have been more interested in the fact that it was frontal (the older debate) than in its one-sidedness. Brown-Sequard did not accept Broca's findings because of his general opposition to specific locations for particular functions; but he enthusiastically revived Wigan's notions of duality, without developing them further.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3326018 TI - Relaxation training and home practice in the treatment of anxiety. PMID- 3326019 TI - Assessing the effects of psychotherapy. I. Analysis and critique of present conventions of estimating change. AB - The use of the difference between pre- and posttherapy status as an estimate of change and of the regression transformation as an adjustment for initial status variation is discussed in reliability and scaling terms. Also, the quantitative view of psychotherapeutic change implied by difference scores is set in contrast to a qualitative view of change as inner (re)structuring. Further, it is argued that psychotherapeutic goals should be conceived in terms of metapsychology rather than as the acquisition of desirable surface traits. Finally, the therapeutic and research consequences of testing and interviewing are compared. PMID- 3326020 TI - [Significance of psychosomatic concepts for rehabilitation of patients following myocardial infarct: remarks on a controversy]. PMID- 3326021 TI - [Guidelines for the psychotherapeutic management of schizophrenic patients. What do various schools and methods have in common?]. PMID- 3326022 TI - Heart transplant candidates rejected on psychiatric indications. PMID- 3326023 TI - Calcium channel blockers in psychiatry. PMID- 3326024 TI - [Analysis of errors in imaging diagnosis of varicocele. Duplex sonography, plate thermography and phlebography]. AB - Comparative investigations were done by duplex sonography, thermography and phlebography in 142 patients with 158 varicoceles. Verification of clinical varicoceles (130/158) was performed by duplex sonography in all cases and by thermography in 93%. Measurement errors were due to dorsally located varicoceles near the radix of the penis (3/130) and by small, two-sided varicoceles (6/130). Small subclinical varicoceles (28/158) were detected by real-time sonography in 89%, by Doppler sonography in 64%, and by thermography in 53%. In three patients with normal real-time sonography, subclinical varicoceles were found by Doppler sonography alone. The combination of both sonographic methods is highly sensitive for the detection of subclinical varicoceles and should be done in all cases without therapeutic results. PMID- 3326025 TI - Comparative study between iohexol and iopromide for aortofemoral arteriography. AB - A double-blind clinical trial was performed on 50 patients in order to compare omnipague (iohexol) and Ultravist-300 (iopromide) for peripheral arteriography. Both contrast media were well tolerated, but there was less body heat and pain in the Ultravist group. There were no idiosyncratic reactions or significant changes in blood pressure before and after the injection. PMID- 3326026 TI - Pharmacogenetics and its clinical implications: N-acetylation polymorphism. PMID- 3326027 TI - Pharmacology of local anesthetic agents. PMID- 3326028 TI - Ribonucleotide reductase inhibitors as anticancer and antiviral agents. PMID- 3326029 TI - Enzyme inhibitors of the renin-angiotensin system. PMID- 3326030 TI - Cooperative effects in drug-DNA interactions. PMID- 3326032 TI - Risk assessment problems in chemical oncogenesis. PMID- 3326031 TI - Quinolones. PMID- 3326033 TI - The pharmacology of caffeine. PMID- 3326034 TI - In vitro models for the study of antibiotic activities. PMID- 3326035 TI - Light and dark as a "drug". PMID- 3326036 TI - High resolution nuclear magnetic resonance spectroscopy of biological samples as an aid to drug development. PMID- 3326037 TI - Treatment of helminth diseases--challenges and achievements. PMID- 3326038 TI - Messenger RNA capping enzymes from eukaryotic cells. PMID- 3326040 TI - Proteins covalently linked to viral genomes. PMID- 3326039 TI - Foreign gene expression in plant cells. PMID- 3326041 TI - The genome of Mycoplasma capricolum. PMID- 3326042 TI - Transport of mRNA from nucleus to cytoplasm. PMID- 3326043 TI - Membrane glycoconjugates as potential mediators of alcohol effects. AB - 1. Membrane glycoconjugates include glycoproteins and glycolipids that have many important functions in a wide variety of tissues, especially brain. 2. Alcohol's ability to fluidize and swell plasma membranes could be expected to alter the orientation and conformation of the embedded glycoconjugates. 3. Both kinds of glycoconjugates can contain terminal moieties of sialic acid, which has been shown to be decreased by single doses of alcohol. Chronic exposure to alcohol may have no effect on sialic acid, except in very young animals. 4. Glycolipids containing sialic acid (gangliosides) are also decreased by acute doses of alcohol, but chronic alcohol has little effect. Thus, gangliosides may have a role in the development and expression of tolerance. 5. Glycoproteins containing sialic acid may also be involved in alcohol action, but there has been less research in this area. 6. Alcohol-induced disruptions in membrane glycoconjugates could affect the important cellular functions that glycoconjugates have, and thus research on alcohol effects on glycoconjugates could lead to important discoveries of diagnostic and therapeutic value for alcohol abuse and alcoholism. PMID- 3326044 TI - Treatment of alcohol organic mental disorder with piracetam. AB - 1. The paper presents an investigation of the efficiency of piracetam in alcohol organic mental disorder. 2. A double blind placebo controlled study design was used to compare two dosages of the substance (2 x 3g versus 2 x 12g). 3. The cognitive functions of the patients, especially short term memory and concentration, were assessed on the days 0, 7, 14, 28 and 42 using various psychological instruments. 4. An analysis of 39 patients showed an improvement of cognitive functions in all three groups. 5. Patients receiving drug treatment showed earlier responses than patients receiving placebo; differences between the three investigational groups were not statistically significant. 6. The results achieved make the effect of piracetam appear somewhat questionable. PMID- 3326045 TI - [Lipophorin in insects]. PMID- 3326046 TI - [Molecular theory of the catalytic function of phospholipase A2]. PMID- 3326047 TI - [Alexander Mitscherlich's "Rider Book"]. PMID- 3326048 TI - [The mourning process of the von Humboldt family]. PMID- 3326049 TI - [Marc Chagall--approaches to a psychobiography]. PMID- 3326050 TI - [Acute peritonitis--current clinical classification]. PMID- 3326051 TI - [Hypercalcemia: increasing diagnostic possibilities increase the number of known causes]. PMID- 3326052 TI - [Dr. Feliks Jelonek--physician, lover of the Tatra mountains and writer]. PMID- 3326053 TI - [Syndromes resembling systemic scleroderma induced by chemical agents]. PMID- 3326054 TI - [Current criteria of brain death]. PMID- 3326055 TI - [Stanislaus Augustus at the Krzeszowice health resort]. PMID- 3326056 TI - gamma 2-[corrected]-MSH-like immunoreactivity in porcine pituitary and adrenal medulla. An immunochemical and immunocytochemical study. AB - A sensitive and specific radioimmunoassay for gamma 2-melanotropin (gamma 2-MSH) has been developed that does not recognize alpha-, beta-, gamma 1- or gamma 3 MSH. gamma 2-MSH-like immunoreactivity could be demonstrated in the porcine pituitary and adrenal gland. The highest concentrations were detected in the neurointermediate lobe regardless of extraction procedure. The anterior lobe harboured lower concentrations and in adrenal gland extracts only small amounts were measured. Gel chromatography and high performance liquid chromatography of extracts of both pituitary and adrenal gland revealed several peaks of immunoreactive material, one of which eluted close to the position of synthetic gamma 2-MSH. By immunocytochemistry gamma 2-MSH immunoreactivity was localized to the adrenocorticotropin/alpha-MSH cells in the pituitary and to a subpopulation of the noradrenaline-storing cells in the adrenal medulla. Together, the immunocytochemical and immunochemical findings indicate the existence of gamma 2 MSH-like material in the porcine pituitary and adrenal medulla. PMID- 3326057 TI - [Prenatal irradiation and developmental disorders of the brain--present state of investigation and the problem]. PMID- 3326058 TI - The role of metabolism in the testing of developmental toxicants. AB - The delivery of potential developmental toxicants to the conceptus is dependent on several metabolic and pharmacokinetic factors. Within the maternal embryo/fetal unit, maternal, placental, and embryo/fetal factors must be considered. These factors include blood flow, permeability, biotransformation, and elimination. Pharmacokinetic models based on data gathered from appropriate in vivo and in vitro studies may be used to describe the effect of these factors on toxicant delivery to the conceptus. Several known human developmental toxicants are discussed in terms of the metabolic and pharmacokinetic factors controlling their delivery to the conceptus. Metabolic events, including activation and/or detoxification, have been reported for the majority of the toxicants examined. Thus it would appear that the role of metabolism should be considered during the testing of potential developmental toxicants. PMID- 3326059 TI - A new approach for using short-term tests to screen complex mixtures. AB - This paper suggests a framework for developing parsimonious batteries of rapid, inexpensive biological assays which provide quantifiable estimates of human risk. The framework for the statistical design is tier testing. The framework develops an unusual perspective for using chemical spiking to evaluate the toxicity of a complex mixture to a battery of bioassays. This framework allows immediate evaluation of hazardous wastes and identifies important problems to provide focus for basic research. PMID- 3326060 TI - Design and interpretation of bioassays for carcinogenicity. AB - A description is presented of the difficulties often met in developing meaningful scientific discussions regarding regulatory policy, with examples. In particular, the design and interpretation of rodent bioassays evoke strong emotional responses in many areas. It is suggested that interested parties engage in a scientific debate on some of the more important issues in the appropriate journals, with the purpose of seeking consensus whenever that may be found. PMID- 3326061 TI - Toxicology then and now. AB - A review of the history of the evolution of the science of toxicology from the original concepts of Paracelsus through the early development of analytical chemistry and its contributions to the detection of toxic substances in foods and drugs as these have led to modern regulatory rules for public protection is presented. The legal actions taken to protect against adulteration of food prior to the early steps by the U.S. Department of Agriculture that concluded with the passage of the 1906 Food and Drug Act are systematically documented. The history is reviewed of the Food and Drug Administration's role in the use of animal toxicity studies to develop reasonable criteria for safety of foods and drugs for man. Modern concepts of molecular distribution, metabolism, and excretion of substances in the animal body are discussed as these impinge on the so-called "protection index." The legal and often litigious controversies over the claimed carcinogenicity of chemical substances is documented with comments on the Delaney dilemma and the role of in vitro tests in toxicology. The review concludes with a discussion of the hazards of use of stochastic mathematical models to assess carcinogenicity and suggests that the criteria employed in the report of the Scientific Committee of the Food Safety Council are properly structured to give a contemporary evaluation of all the currently available data. References give documentation of events over the past 200 years that explain the present state of toxicology as a discipline. PMID- 3326062 TI - [Value and limitations of echography in oral medicine]. PMID- 3326063 TI - [The use of non-precious metal alloys for dental crowns and bridges. A review of the literature. 3]. PMID- 3326064 TI - [The oral medicine of Govert Bidloo (1685), William Cowper (1698) and James Drake (1707)]. PMID- 3326065 TI - [Congenital pseudarthrosis of the tibia and fibula in children. Results of the treatment of 18 cases with nails and bone grafts]. AB - Eighteen cases of congenital pseudarthrosis of the leg in 17 children were treated by nailing and tibio-fibular graft with a mean follow-up of six years (from one to twelve years). Six patients had reached the end of growth. Primary union was obtained in 17 cases in a mean time of 6.5 months (from 3.5 to 18 months), but one case developed a new pseudarthrosis at the level of an associated upper tibial osteotomy. Only one case required a supplementary graft. Walking was usually achieved without any apparatus after five-and-a-half months, the tibia being protected by a nail which was left in place until the end of growth. In two cases, a fracture produced by trauma occurred in the limb long after consolidation. These two fractures healed in the normal time. Inequality of limb length was present in all the cases, but its progress varied. On three occasions it was treated by femoral lengthening. Stiffness of the ankle and subtaloid joints resulted from nailing of the hindfoot in nine cases and improved very little after freeing of the joints. The use of telescopic rods avoids the need for further operations to change the rod during growth. We consider that this is a reliable method but that, in certain cases, the effects on growth and on the foot can be diminished by appropriate modifications of technique. PMID- 3326066 TI - [Coverage of cutaneous loss of substance in the lower limb]. AB - In the light of 10 years experience with more than 200 operative cases, the author presents the various operative techniques for the cover of skin loss in the lower limb. The different techniques are reviewed: muscle rotation flaps, myocutaneous flaps, pure cutaneous flaps, neurovascular island flaps and free vascular flaps. These procedures are described in detail, particularly those most often used. Indications are considered in terms of levels. At the present time, the author's preference is for muscle rotation or cutaneous flaps; his use of free vascular flaps has much diminished in recent years. The indications also depend on the patient's age, the condition of his joints and the state of his vessels. PMID- 3326067 TI - [Development of antitumor drugs: current and future situation]. PMID- 3326068 TI - [Lymphoid neoplasms after therapy with hydantoins. Study of 5 cases and review of the literature]. PMID- 3326069 TI - [Pre-S proteins in hepatitis B]. PMID- 3326070 TI - [Treatment of peptic ulcer: an economics perspective]. PMID- 3326071 TI - [Research in pediatric nursing]. PMID- 3326072 TI - [A thesaurus in Portuguese for nursing: the elaboration of a vocabulary of descriptors--1]. PMID- 3326074 TI - [Electrophysiology and analysis of the image of the development of Purkinje cells in culture and in the intact animal]. AB - The electrophysiological and morphological properties of the Purkinje cells (P cells) grown in organotypic cultures were studied in HRP intracellulary labelled neurons and compared to Golgi stained P cells from kitten of different ages. The effects of afferent fiber depletions on the final dendritic topological parameters were investigated by 3-dimensional reconstructions and computerized methods. In culture, the P cell dendritic trees always appeared reduced in size when compared to their in vivo counterparts. A discriminant analysis permitted the recognition of 3 populations of cultured P cells according to the type of deafferentation. In intact animals, the dendritic organization appeared biplanar around day 13. These results demonstrate that the presence of all normal inputs is required to achieve the full elaboration and the monoplanar disposition of the P cell dendrites. PMID- 3326073 TI - [The concept of biological rhythm in psychopathology]. AB - The chronobiological hypotheses of depression are based on epidemiological, biological as well as therapeutical pieces of evidence. The seasonal pattern of depression and suicide rates tend to link affective disorders and the daylight duration. Disturbances of circadian rhythms have been reported in endogenous depression. Treatments of depression, such as manipulations of the sleep/wake cycle, phototherapy or tricyclics, may involve chronobiological mechanisms on endogenous pacemakers. Beside the phase advance hypothesis of depression, present data seem to involve a disturbance of the mechanisms of entrainment of the internal clocks by external synchronizers. Other psychiatric illnesses may thus be linked to chronobiological abnormalities. PMID- 3326075 TI - [Hepatic nodular regenerative hyperplasia: apropos of a case and review of the literature]. PMID- 3326076 TI - [The ileocecal sphincter in the functional dynamics of the digestive tract: collective review]. PMID- 3326077 TI - [Structure of the neural plexus of the gallbladder of dogs]. PMID- 3326078 TI - [Arterial hypertension in the adult]. PMID- 3326079 TI - [Acquired immunodeficiency syndrome]. PMID- 3326080 TI - Failure of diterpenes from Jatropha curcas to induce mutation in Salmonella typhimurium TA98 and TA100. AB - No mutagenicity of five diterpenes isolated from the roots of Jatropha curcas was detected by Ame's test using both TA98 and TA100 tester strains with or without S 9 fraction from livers of rats treated with polychlorinated biphenyl. PMID- 3326081 TI - Intravenous platelet activating factor does not affect lung epithelial permeability. AB - Administration of platelet activating factor has been shown to produce lung edema in several species including the rabbit. To determine if platelet activating factor increases lung alveolar epithelial permeability, we studied the effect of intravenous platelet activating factor administration on clearance of 99mTc-DTPA from the lung of the rabbit. Intravenous platelet activating factor produced marked hemodynamic and cellular responses but did not increase the clearance of 99mTc-DTPA from lung to blood. We conclude that although platelet activating factor can induce lung edema in the rabbit, it does not produce an acute increase in alveolar epithelial permeability. PMID- 3326082 TI - Effects of continuous positive airway pressure in acute asthma. AB - We studied flow changes, airway pressures, breathing patterns and subjective sensation during tidal breathing on continuous positive airway pressure (CPAP) in 21 acutely ill asthmatic patients and 19 controls. The measurements obtained at various levels of CPAP were compared to the value at zero end-expiratory pressure. The fractional inspiratory time (TI/TTOT) was significantly reduced in both the patients and the control group (p less than 0.01). Patients noticed the best sensation of comfort at CPAP of 5.3 +/- (SD) 2.8 and the control group at 1.6 +/- 2.5. We noted a reduction in peak tidal expiratory flow and an increase in late-phase expiratory flow during tidal breathing in both groups although these changes were not statistically significant. There was improvement in sensation of comfort during low to medium levels of CPAP in acutely ill asthmatics. We conclude that low to medium levels of CPAP may be beneficial in acute asthma by assisting inspiratory muscles. As CPAP is increased, the beneficial effects of increased end-expiratory flow rate may be offset by the reduction in peak tidal expiratory flow rates. PMID- 3326084 TI - Idiopathic and symptomatic plastic bronchitis in childhood. A report of three cases and review of the literature. AB - During a one-year period we could observe 3 children with the rare disease of plastic bronchitis. Two of them showed a symptomatic form, one with constrictive pericarditis, the other with bronchial asthma as primary diseases. No underlying disease could be found in the third case. Bronchial casts had to be extracted during endoscopy in all children. No relapse occurred after 2-3 years. Reviewing the literature, 37 cases of plastic bronchitis in childhood could be found, most of them had been reported before 1954. PMID- 3326083 TI - Fiberoptic bronchoscopy in the diagnosis of pulmonary lymphomas. AB - Fiberoptic bronchoscopy was useful for the diagnosis of 7 of 9 pulmonary lymphomas (5 primary lung lymphomas, 4 lung involvement in systemic disease). Radiologic and endoscopic findings were variable. The importance of immunohistochemical markers for successful diagnosis is emphasized. PMID- 3326085 TI - [Disorders of respiration in patients before and after liver transplantation]. AB - In 61 patients with chronic hepatic insufficiency parameters of regulation of ventilation, mechanics of breathing and gas exchange were determined pre and in 16 patients post liver transplantation. Preoperatively disturbances of control with increased central respiratory drive resulting in chronic hyperventilation and maladaptation of perfusion to ventilation were found. Successful liver transplantation resulted in regression of these disturbances to different degrees. We therefore conclude that disturbances of respiration in patients with chronic hepatic insufficiency are reversible after successful liver transplantation. PMID- 3326086 TI - [Intracellular calcium measurement using X-ray microprobe analysis]. PMID- 3326087 TI - The common and uncommon clinical presentations and treatment of periodontal disease in the dog and cat. PMID- 3326089 TI - Stagnant loop syndrome in the dog and cat. PMID- 3326088 TI - Indications and techniques of partial gastrectomy in the dog. PMID- 3326090 TI - The use of adsorbents to treat gastrointestinal problems in small animals. PMID- 3326091 TI - The role of gastrointestinal immunity in parasitic infections of small animals. PMID- 3326092 TI - Acute pancreatitis: diagnostic dilemmas. PMID- 3326093 TI - Hepatic pathophysiology and biopsy interpretation. PMID- 3326094 TI - Identification and surgical management of portosystemic shunts in the dog and cat. PMID- 3326095 TI - Microbial content in fresh vegetables: roots, tubers and bulbs. PMID- 3326096 TI - [Leishmaniasis in Mexico]. PMID- 3326097 TI - [Alternative technologies for alcoholic fermentation in Saccharomyces cerevisiae]. PMID- 3326098 TI - Ethanol fermentation of enzymatically hydrolysed leached beet cosette using Trichoderma harzianum cellulases and Saccharomyces cerevisiae. PMID- 3326099 TI - [A new medium for the isolation, culture and identification of Mycobacterium]. PMID- 3326100 TI - Laboratory diagnosis of Trichomonas vaginalis among women attending a venereal diseases control division. First report. PMID- 3326101 TI - Refractory hypertension in childhood--efficacy of captopril therapy. AB - Because of the advance of techniques and age-matched apparatus for blood pressure measurement, and because of the availability of age-related normal values in childhood, the knowledge of the number of children having elevated blood pressures has recently improved. In a group of healthy children, the first important task is to determine how many incidences of "essential hypertension" there are among them, which may appear in childhood and persist into adulthood. This should urge us to undertake periodical examinations of healthy children. On the other hand, the treatment of "secondary hypertension" has similarly been improved. Since 1979 in particular, captopril, an orally active angiotensin I converting enzyme inhibitor, has successfully been administered to treat children with malignant hypertension and who respond poorly to conventional antihypertensive therapies. We report 3 cases that received captopril for refractory hypertension: a 2-year-old boy with renal and renovascular anomalies, a 7-year-old boy with moyamoya disease after surgical operation, and a 17-year old youth with Cushingoid syndrome due to chronic administration of steroids against mixed connective tissue disease. After the introduction of captopril, good pressure control was obtained in all 3 cases, although reasonable effects of measurement values of the renin-angiotensin-aldosterone system (decrease in angiotensin I & II, increase in I/II ratio, etc.) were found only in the first case. PMID- 3326102 TI - [The difficulty of distinguishing retroperitoneal schwannoma from liver tumor in the caudate lobe]. AB - A 68-year-old woman was admitted to our hospital for the evaluation of an abdominal tumor. Both ultrasonography and computerized tomography revealed a mass at the caudate lobe of the liver. However, it was difficult to distinguish the mass from a liver tumor in the caudate lobe. The laboratory data showed only a slight elevation of the serum gamma-GTP level and ICG retention. The abdominal arteriography revealed a vascular tumor located in the retroperitoneal space, which was receiving its blood supply from the right inferior phrenic artery. When a laparotomy was performed, a yellowish solid mass (8 X 6 X 4.5 cm) was found behind the lateral segment of the left liver lobe. Histological examination showed interlacing bands of uniform spindle cells of which elongated nuclei were arranged in a palisading pattern. The tumor was diagnosed as schwannoma. Literatures on retroperitoneal schwannoma are reviewed, as this tumor is relatively rare. PMID- 3326103 TI - Statistical facts about cancers on which Doctor Rigoni-Stern based his contribution to the Surgeons' Subgroup of the IV Congress of the Italian Scientists on 23 September 1842. (translation) PMID- 3326104 TI - Some points on the use of 'independent Bayes' to diagnose acute abdominal pain. AB - This paper outlines some of the difficulties encountered when using independent Bayes as a statistical decision aid for acute abdominal pain. Methods of reducing the resultant problems are suggested. Restriction of the number of facets in the system reduces violation of the simplifying assumption of symptom independence without adversely affecting efficiency. Introduction of a realistic utility structure is investigated as is the potential transportability of the decision aid. Generalizations of the results are discussed and potential uses of medical decision aids are considered. PMID- 3326105 TI - Improved estimates of discordance ratios in twin studies. AB - In the study of monozygotic twins relative to disease and risk factors, particular interest focuses on the subset who are discordant for some suspected risk factor (for example, smoking), since such twins constitute a natural case control pair. In such studies, questionnaires designed to identify the status of all twin pairs are sometimes error prone and can yield misleading estimates of the concordance-discordance ratios. Greater efforts to verify the characteristics of apparently discordant pairs than to verify those of apparently concordant pairs can result in the 'unequal ascertainment' fallacy. Using the results of a questionnaire with known error rates and the 'apparent' frequencies yielded, we present unbiased, maximum likelihood estimates of the 'true' proportions of concordant and discordant pairs. concordant and discordant pairs. We also present approximate covariances among these estimates. PMID- 3326106 TI - [The life and works of Robert Danis]. PMID- 3326107 TI - [Some current data on immunopharmacology]. PMID- 3326108 TI - [Skin tumors with fibroblastic differentiation]. PMID- 3326109 TI - [Dengue and yellow fever arboviruses]. PMID- 3326110 TI - [Wobe-Mugos: a proteolytic enzyme combination for tumor therapy. Documentation No. 7]. PMID- 3326111 TI - [Polyneuropathies during prolonged stays in resuscitation]. AB - Extensive multiple neuropathies were observed in four patients after prolonged stay in intensive care units. Date of onset of the multiple disorders was difficult to determine due to disturbed consciousness of all patients during the first few weeks of intensive care: it was probably between the 10th and 30th days. Electrophysiological examinations in the 4 patients, and ultrastructural study of musculocutaneous nerve of leg in 2 cases, suggested an acute axonal lesion. All patients survived the causal affection which had justified prolonged intensive care, 3 recovering from the multiple neuropathy within 3 to 4 months, the last patient having marked neuromuscular sequelae. Several factors can be incriminated at the origin of this multiple neuropathy. Whereas retrospective studies allowed exclusion of a toxic, infectious or drug-related cause, severe nutritional deficiencies existed; proteins in all cases and vitamins in one patient despite enteral re-nutrition judged as satisfactory. Additionally, a role for a previous lesion of peripheral nerves from chronic hypoxia was possible in 2 cases as well as for a non-insulin dependent diabetes in one of these two patients. A rarely reported but probably not exceptional complication, diagnosis is assisted by early electrophysiologic exploration. Correction of nutritional disorders may require parenteral feeding exclusively, this possibly accelerating neurologic recovery, as proposed in the several rare studies reported in the literature. PMID- 3326112 TI - [Behcet's diseases with multiple intracranial arterial aneurysms]. AB - A case of multiple intracranial arterial aneurysms occurring in a 43 year-old patient with an 8-year history of Behcet's disease is reported. The diagnosis was based upon the past occurrence of polyarthritis, oral and scrotal aphthous ulcers and cutaneous hypersensitivity. There was a three year remission after a brief treatment with corticosteroids. At the end of this period, a left hemiplegia occurred. CT scan showed an infarction in the right middle cerebral artery territory. Angiography showed fusiform aneurysms of the intracranial right internal carotid, right anterior and middle cerebral arteries. The draining veins and sinuses were normal. Careful angiographic examination of visceral and peripheral arteries showed only bilateral retinal artery aneurysms. Large artery involvement is a rare complication of Behcet's disease, and a thorough review of the literature showed only one reported case of an intracranial aneurysm. PMID- 3326113 TI - Dose-response effects of zopiclone on night sleep and on nighttime and daytime functioning. AB - Six normal volunteers, aged 20 to 39 years, underwent 2 adaptation nights and three sessions of 2 consecutive experimental nights and days at 1-week intervals, according to a latin-square design. In the three sessions, subjects received either zopiclone, 3.75 mg or 7.5 mg, or placebo at 2215 h in a double-blind protocol. On nights 1 and 2 of each session, subjects were continuously monitored polygraphically, except for a 45-min provoked wake episode 135 min after sleep onset on night 2. Degree of daytime somnolence was assessed during day 1 by means of a multiple sleep latency test (MSLT) and performance evaluation was carried out during night 2 (0000 h) and day 2 (800 h and 1200 h) by means of a battery of four tests. NREM sleep stages 3 and 4 increased significantly after 3.75 mg and 7.5 mg zopiclone (p less than 0.05). No significant differences between placebo and 3.75 mg and 7.5 mg zopiclone were found at any time in the MSLT. Two performance tests (eye-hand coordination test and choice reaction time test) showed a highly significant impairment (p less than 0.01) at 0000 h with 7.5 mg zopiclone; one test (eye-hand coordination test) showed a significant impairment (p less than 0.05) at 0800 h also with 7.5 mg zopiclone and none at 1200 h. From a subjective point of view, depth and quality of sleep were improved, whereas number of awakenings and feeling on awakening were not modified. Side effects (bitter taste, jitteriness, difficulty to concentrate) were reported only with 7.5 mg zopiclone. PMID- 3326114 TI - Efficacy of zopiclone in middle age. AB - Effects of zopiclone (5.0, 7.5, and 10 mg) on sleep and on performance were studied in middle-aged subjects. Zopiclone (5.0-10.0 mg) reduced awake activity and the number of awakenings, and increased the duration of stage 2 sleep. The appearance of REM sleep was delayed, but this effect was without reduction over the whole night. There were no impairments in the digit symbol substitution test when zopiclone was compared with placebo, although there were less substitutions with 10.0 mg than with 5.0 mg. Symbol copying and choice reaction time were unaltered. Zopiclone would appear to be a useful hypnotic for those involved in skilled work. Based on the results obtained in healthy volunteers, the 5.0 mg dose would be appropriate for many; if in insomniac patients, 7.5 mg was needed, then it is likely to be free of undue impairment of performance the next day. PMID- 3326115 TI - Residual effects of zopiclone (Imovane). AB - A double-blind, randomized, cross-over study has been conducted with zopiclone (Imovane), a new cyclopyrrolone hypnotic in ten healthy volunteers. Hypnotic efficacy has previously been demonstrated at a dose of 7.5 mg. The present study was designed to determine the overnight residual effects of different doses of the drug ranging from 2.5 to 10 mg. Measurement of complex reaction time was used as an objective test of impairment of psychomotor function. To supplement this, the volunteers were asked to report, by means of visual analogue scales, any perceived changes in their performance in the complex reaction time test, in their mood, and in the onset and quality of sleep. Complex reaction time testing revealed no significant impairment except at 12 h after the 10 mg dose. Subjective assessments of onset of sleep showed a dose-dependent shortening of sleep latency, confirming the hypnotic action of the drug. Volunteers were aware of a decline in psychomotor performance, of some sleepiness on awakening, and decreased alertness after previous night doses of 7.5 and 10 mg. It is concluded that a dose of 7.5 mg is optimal, producing significant hypnotic effect with minimal residual impairment. PMID- 3326117 TI - Chronic administration of zopiclone and nitrazepam in the treatment of insomnia. AB - The hypnotic effects of 7.5 mg zopiclone, as well as its unwanted and residual effects, were compared with those of 5 mg nitrazepam in a double-blind, randomized, multicenter, parallel group study. After an initial, 7-day, placebo wash-out period, insomniac out-patients under the care of general practitioners received either 7.5 mg zopiclone or 5 mg nitrazepam for 6 weeks. Everyday, the patients filled in a diary (analogue scales for sleep parameters and condition during daytime); a sleep questionnaire was filled in at baseline and at the end of active treatment period; every 2 weeks, a somatic complaint check-list inventory and a mood rating scale were filled in and psychomotor tests performed; and at the end of the study, a global evaluation of efficacy and acceptability was given by the investigator. Clinical laboratory tests were performed before and after the active treatment period. From the diary, sleep onset latency, as well as sleep quality, were similarly improved by both drugs throughout the whole study. From the sleep questionnaire, all sleep parameters measured were improved at the end of the 6-week treatment period in both groups. No statistical differences in the various psychomotor tests were observed between the two treatment groups, and a significant improvement in the working ability of patients was noted with both drugs. Some significant differences were observed in the mood rating scale and the somatic complaint check list, probably related to differences in pharmacokinetics of the two drugs. PMID- 3326116 TI - Zopiclone and nitrazepam: a multicenter placebo controlled comparative study of efficacy and tolerance in insomniac patients in general practice. AB - The efficacy and tolerance of zopiclone were compared with nitrazepam and placebo in a multicenter double-blind parallel-group study in insomniac patients. Following a 7-day placebo washout period, 99 patients (age range 20 to 69 years) received oral capsules of 7.5 mg zopiclone or 5 mg nitrazepam or placebo for 2 weeks. During the fourth week all patients received placebo treatment. Sleep assessments by the patients showed that, compared with placebo, zopiclone and nitrazepam improved all sleep measures of efficacy from the first night and that effectiveness was maintained throughout treatment. The physicians global assessment of efficacy also favored zopiclone and nitrazepam over placebo treatment. Subjective morning drowsiness during treatment was significantly less for zopiclone than for either nitrazepam or placebo and represents a clear advantage for ambulatory patients. No rebound insomnia was evident during a 7 day post-treatment withdrawal period for either zopiclone or nitrazepam. Tolerance was good for all treatments. PMID- 3326119 TI - Mixed bacterial meningitis. AB - Two recent cases of mixed bacterial meningitis at the Kansas City Veterans Administration Medical Center were studied. A review of the literature suggests that 1% of all cases of meningitis are caused by more than one bacterial species. Before 1950 such cases occurred predominantly in children and were caused by combinations of bacteria commonly associated with meningitis. Since 1950 a largely adult population has been affected by mixed bacterial meningitis, with a higher incidence of gram-negative bacillary organisms cultured from the cerebrospinal fluid. Common predisposing factors in this older group of patients include infection at contiguous foci, tumors in close proximity to the central nervous system, or fistulous communications with the central nervous system. Mortality was 26% for cases occurring before 1950 and 63% for those occurring after 1950. Failure to recognize one of the organisms present in the cerebrospinal fluid may result in the initiation of inadequate therapy in as many as 67% of cases. Empiric broad-spectrum antimicrobial therapy is indicated in symptomatic patients predisposed to mixed bacterial meningitis until culture results become available. PMID- 3326118 TI - Zopiclone versus nitrazepam: a double-blind comparative study of efficacy and tolerance in elderly patients with chronic insomnia. AB - A randomized, double-blind, comparative trial of zopiclone versus nitrazepam was conducted in 74 geriatric chronic insomniac patients. Following a 7-day wash-out period, two parallel groups, successively received a placebo for 7 days, then either 7.5 mg zopiclone or 5 mg nitrazepam for another 7-day period. Efficacy on sleep was assessed by a sleep analogue scale and the Spiegel Sleep Questionnaire, residual effects by psychometric tests and tolerance by a standardized question, as well as by clinical and laboratory tests. Zopiclone and nitrazepam were more active than placebo on all tests of efficacy. In contrast with nitrazepam, zopiclone was devoid of effect on neurological function. In addition, the condition on awakening was better with zopiclone. PMID- 3326120 TI - Influence of subinhibitory concentrations of antibiotics on virulence of staphylococci. AB - The understanding and control of infections caused by staphylococci are still far from complete, and staphylococcal infections continue to be a serious problem. The organisms possess numerous virulence factors that can act independently to induce various symptoms and lesions. Chemotherapy has changed the clinical spectrum of staphylococci but has not eradicated serious staphylococcal infections. An evaluation of the interaction of antibiotics, staphylococci, and host defense will help to identify those factors that determine the success or failure of therapy for staphylococcal infections. The activity of antibiotics is usually expressed in terms of concentrations that either inhibit or kill microorganisms in vitro or in experimental infections. Subinhibitory concentrations of antibiotics may induce changes in bacterial properties both in vitro and in vivo. An understanding of the mechanism of such changes would allow a more rational application of antibiotics that have both specific antistaphylococcal action and positive effects on host defense mechanisms. PMID- 3326121 TI - Does serum protein binding inhibit tissue penetration of antibiotics? AB - Accumulated data on the penetration of 15 antibacterial agents into peripheral human lymph are reviewed. The major factor determining extravascular penetration is the level of serum protein binding. The penetration ratios of extravascular and serum levels diminish gradually as the level of protein binding increases. However, even at the highest protein-binding levels, distinct lymph concentrations are observed. The degree of penetration ranges from 100% for the antibiotic with the lowest level of serum protein binding (gentamicin, no drug bound) to 20% for that with the highest level of protein binding (flucloxacillin, 96% bound). PMID- 3326122 TI - Bacteremia with Anaerobiospirillum succiniciproducens. AB - Anaerobiospirillum succiniciproducens is a motile, spiral anaerobic bacterium with bipolar tufts of flagella. Reports of clinical illness due to A. succiniciproducens are rare. In a retrospective review of anaerobic isolates referred to the Centers for Disease Control (CDC) from January 1, 1975, through January 31, 1986, isolates of A. succiniciproducens from the blood of 21 patients were identified. A single patient whose blood isolate had not been received at CDC was included in the review. These 22 patients were from 15 states. Their mean age was 58.6 years. Underlying disorders included alcoholism, atherosclerosis, malignancy, surgery, diabetes mellitus, and dental caries. Clinical features included gastrointestinal tract signs and symptoms in 17 (77%) of 22, fever greater than 38 degrees C in seven (37%) of 19, and leukocytosis of more than 10,000 cells/mm3 in 11 (58%) of 19. Although 16 patients received antimicrobial therapy, its effect on outcome was unclear. A. succiniciproducens was reported to have contributed to the deaths of seven patients. Disorders predisposing patients to anaerobic infections may put them at increased risk for A. succiniciproducens bacteremia. The presence of antecedent gastrointestinal tract signs and symptoms suggests that the gastrointestinal tract might be the primary portal of entry. PMID- 3326123 TI - Clinical spectrum in 107 cases of toxoplasmic lymphadenopathy. AB - Lymphadenopathy is the most frequent clinical manifestation of acute acquired infection with Toxoplasma in the immunocompetent individual. One hundred seven cases of histologically verified toxoplasmic lymphadenitis were reviewed in an effort to determine the usual modes of clinical presentation and the incidence of extranodal disease. Toxoplasmic lymphadenitis most frequently involved a solitary lymph node in the head and neck regions, without systemic symptoms or extranodal disease and with a benign clinical course. However, serious extranodal disease did occur in some patients and included myocarditis, pneumonitis, encephalitis, chorioretinitis, and transmission of the infection to the fetus. Case histories are presented to illustrate important points with respect to clinical presentation, complications, and diagnosis. PMID- 3326124 TI - Bacteroides fragilis meningitis. AB - Bacteroides fragilis is a rare cause of bacterial meningitis. In the antibiotic era nine cases have been reported. Seven of these nine cases occurred in premature infants and neonates. Of the nine patients with B. fragilis meningitis, two died, four survived with neurologic sequelae, and three survived without sequelae. Predisposing conditions included abdominal sepsis, chronic otitis media, and ventriculoatrial shunt infection. Metronidazole, which is bactericidal, has been the most effective therapy for B. fragilis meningitis. PMID- 3326125 TI - Endocarditis caused by Kingella indologenes. AB - The first known case of endocarditis caused by Kingella indologenes is reported. A review of the literature reveals only seven cases of endocarditis caused by the other two species of the genus Kingella (Kingella kingae, six cases; Kingella denitrificens, one case). Kingella organisms appear to be sensitive to a wide variety of antimicrobial agents. The available data suggest that endocarditis caused by Kingella species occurs rarely and is associated with a benign clinical course. PMID- 3326126 TI - Treatment of pulmonary sporotrichosis with ketoconazole. AB - Antifungal therapy that included ketoconazole failed in a 44-year-old woman with pulmonary sporotrichosis progressing slowly over a seven-year period. On the basis of this case and the modest amount of experience reported in the literature, ketoconazole does not appear to be effective in the treatment of pulmonary sporotrichosis. PMID- 3326127 TI - Alternaria infection in a patient with acquired immunodeficiency syndrome: case report and review of invasive alternaria infections. AB - A 31-year-old man with AIDS developed a necrotic lesion on his nasal septum due to Alternaria alternata. Excision and treatment with amphotericin B resulted in cure. This case expands the spectrum of opportunistic pathogens that infect patients with AIDS. Visceral and mucosal infections due to Alternaria have been reported in at least seven other patients. PMID- 3326128 TI - Brucellar meningitis. AB - Neurobrucellosis develops in less than 5% of cases of systemic brucellosis; however, most patients with neurobrucellosis have meningeal involvement. Seven new cases of brucellar meningitis and 17 cases from the Spanish- and English language medical literature are analyzed in terms of epidemiologic data, clinical manifestations, laboratory results for cerebrospinal fluid and serum, treatment, and course of the disease. Brucellar meningitis mimics other neurologic and non neurologic conditions, and its diagnosis is only suggested in the presence of adequate epidemiologic information. Isolation of Brucella from the cerebrospinal fluid is uncommon. Treatment is accomplished with the combination of tetracycline or doxycycline and streptomycin, rifampin, or both. Mean length of therapy in the seven new cases was 8.5 months. Brucellar meningitis has a better prognosis than other forms of chronic meningitis, and mortality is low for reasons that are not clear; however, the incidence of minor sequelae is high. PMID- 3326129 TI - Epidemiology and ecology of rickettsial diseases in the People's Republic of China. AB - Since 1949, information on rickettsial diseases in the People's Republic of China has been virtually nonexistent in the West. This is the first comprehensive review of the ecology and epidemiology of Chinese rickettsial diseases to be published outside the People's Republic. At least five rickettsioses exist in China: scrub typhus, murine typhus, epidemic typhus, Q fever, and one or more spotted fever-group (SFG) rickettsioses. Although epidemic typhus has been controlled and scrub typhus has abated in many areas, murine typhus, Q fever, and SFG rickettsiosis are important public health problems. Serologic surveys indicate high prevalences of antibodies to Coxiella burnetii, Rickettsia tsutsugamushi, and SFG rickettsiae in some regions; these rickettsiae have been isolated from humans, arthropods, and animals. Doxycycline has emerged as the best treatment for murine typhus, epidemic typhus, and scrub typhus. China offers both opportunities and challenges for the investigation and alleviation of the problems of rickettsial diseases. PMID- 3326130 TI - Fibronectin: a brief overview of its structure, function, and physiology. AB - Fibronectin is a large glycoprotein that is composed of blocks of three types of repeating, homologous peptide sequences. Several of the homologous blocks form functional domains that are organized in a linear array on two nearly identical subunit arms. Specific domains allow fibronectin to promote cell-to-cell adhesion, cell-to-basement-membrane attachment, clot stabilization, embryogenesis, nerve regeneration, fibroblast migration, macrophage function, and pathogen (virus, fungus, bacteria, and protozoa) binding to mammalian cells and extracellular matrix. Thus, this complex and multifunctional protein is involved in the pathogenesis of infections from the initiation of the infection through the final stages of wound healing. PMID- 3326132 TI - Interactions of fibronectin with streptococci: the role of fibronectin as a receptor for Streptococcus pyogenes. AB - Current evidence suggests that lipoteichoic acid (LTA) on the surface of Streptococcus pyogenes is centrally involved in the adherence of these bacteria to the oral mucosa. The major receptor on the surface of buccal mucosal cells for S. pyogenes is fibronectin. Fibronectin is a complex glycoprotein found in blood, extracellular matrices, and saliva. Many species of streptococci bind to fibronectin, although the characteristics of these interactions are different. Furthermore, whereas LTA is an efficient inhibitor of the binding of fibronectin to group A streptococci, it has little ability to inhibit the binding of fibronectin to Streptococcus pneumoniae or Staphylococcus aureus. Studies conducted with fibronectin show that different bacteria bind to different sites. The ability of various bacteria to interact with different domains on the fibronectin molecule may play an important role in bacterial adherence and tissue tropism. PMID- 3326133 TI - Role of fibronectin in the pathogenesis of syphilis. AB - In recent years studies concerned with the attachment of Treponema pallidum to host cells have focused on the possible, role of fibronectin in mediation of this event. Although our understanding of in vitro fibronectin-T. pallidum interactions has increased markedly, considerable controversy exists concerning not only the kinetics of binding but whether fibronectin is the only matrix protein involved in attachment. Moreover, a unifying hypothesis concerned with the role of fibronectin in the pathogenesis of syphilis cannot be limited solely to early events. Further characterization of fibronectin-T. pallidum interactions must also take into consideration that the natural infection, characterized by distinct stages, is accompanied by immunologic responses that undoubtedly impact on those cellular interactions. PMID- 3326131 TI - Adherence of Staphylococcus aureus to squamous epithelium: role of fibronectin and teichoic acid. AB - For bacteria to colonize mucosal surfaces, they must be able to attach to epithelial cells. One of the most important factors in determining this attachment is bacterial adherence. The preferential adherence of a bacteria to a particular tissue influences the site of infection and the virulence of the organism. The glycoprotein fibronectin mediates adhesion of the bacteria to eukaryotic cells. Recent investigations have revealed that the precise locations of the binding sites for Staphylococcus aureus are close to the NH2-terminal and at the COOH-terminal regions of the fibronectin molecule. Teichoic acids are major cell-wall components of staphylococci that have been found to mediate the capacity of the bacteria to adhere to epithelial cells. By use of biologic assays based on the specific adherence of S. aureus to nasal epithelium, it was determined that the binding site for fibronectin appears to be teichoic acid. PMID- 3326134 TI - Fibronectin in parasitic diseases. AB - Fibronectin, a major interstitial matrix protein with binding sites for a variety of molecules and with multiple biologic activities, may play an important role in certain parasitic diseases. Leishmania and Trypanosoma cruzi bind host fibronectin, which, in turn, facilitates their association with the cells they parasitize. Invasive Entamoeba histolytica and Schistosoma produce proteases that degrade fibronectin and other matrix proteins, presumably facilitating the breaching of intestinal mucosa and dermal barriers to infection. The granulomatous inflammation that accompanies tissue deposition of schistosomal eggs promotes excess matrix production and scar formation. Granuloma macrophages and fibroblasts secrete fibronectin, which may serve to recruit additional fibroblasts and also may aid in maintaining the structural integrity of the granulomas. These early findings suggest that parasite-fibronectin interactions may be a fertile area for further research. PMID- 3326135 TI - Role of fibronectin in the pathogenesis of candidal infections. AB - Adherence of Candida albicans yeast cells to mammalian cells in vitro is promoted by a cell-surface adhesin that is probably a mannan or a mannoprotein. This observation is based on results of studies that utilized either lectins or antibodies to Candida that block attachment. Selective enzymatic degradation of cell wall constituents has been used to define the surface ligand of the candidal cell. Recently, nonadhering, spontaneous mutants of C. albicans, from both yeast and mycelial forms, that lack specific mannoproteins have been described. In addition, such mutants are avirulent, an indication that attachment plays a role in the disease process. The mammalian receptor for Candida has not been identified, but in endocarditis it could be fibronectin, both because fibronectin is present at the endocardial lesion and because those Candida species that bind to fibronectin in vitro exhibit a high disease potential; i.e., Candida species that bind to fibronectin in vitro also cause endocarditis, while those that do not bind in vitro do not cause disease. Attachment of yeast cells both to human buccal and vaginal epithelial cells is reduced significantly if yeast cells are preincubated with fibronectin, a finding that indicates a possible role for fibronectin as the epithelial surface receptor for Candida. PMID- 3326137 TI - Fibronectin: an enhancer of phagocyte function. AB - Although fibronectin does not act as a direct opsonin as originally described, it does mediate important interactions with phagocytes throughout the inflammatory process. Fragments of fibronectin released by neutrophil proteases are chemoattractants for monocytes. Moreover, subendothelial matrix fibronectin and "inflammatory" fibronectin released from phagocytes enhance phagocyte adherence to host tissues at an inflammatory site. Fibronectin also increases chemokinesis. Once the phagocyte enters tissues, fibronectin promotes C3- and Fc-receptor activation, allowing complement-coated bacteria to be ingested. Finally, fibronectin enhances the bactericidal activity of monocytes. Thus, fibronectin plays an important, but indirect role, in the activities of phagocytes. PMID- 3326136 TI - Fibronectin and viral pathogenesis. AB - Fibronectin is a dimeric high-molecular-weight glycoprotein composed of two similar but not identical subunits. Differences have been observed between plasma and cell-derived fibronectins, and molecular and sequencing studies have revealed a domain structure. The characteristic features of fibronectin include its various molecular and biologic interactions, which can be assigned to the different domains of the molecule. Fibronectin was originally discovered as a protein missing from the surfaces of virus-transformed cells. The importance of functional oncogenes in the loss of extracellular matrices was later established in a number of studies using virus mutants that are temperature-sensitive for transformation. The loss of the extracellular matrix appears to be a result of multiple events in cells but is not a prerequisite for malignant growth in vivo. There appear to be multiple transformed phenotypes, and the loss of extracellular fibronectin may be due in part to proteolytic activity by the cells and other alterations caused by functioning oncogenes. The wide distribution of tissue and soluble forms of fibronectin offers multiple occasions for interactions with other molecules. Binding of fibronectin to viruses and purified viral proteins has been observed in a number of studies. Neuraminidase-sensitive virus-binding sites in the fibronectin molecule have tentatively been identified. Fibronectin also is capable of binding to various complement components, possibly making clearance of viral antigen-antibody-complement complexes, which are observed in the circulation during viral infection, more rapid. The virus-binding ability of fibronectin may play a role in modifying viral infections in the body. PMID- 3326139 TI - [Observations on the sensitivity to antibiotics and chemotherapeutic agents of E. coli strains]. PMID- 3326138 TI - Plasma fibronectin and fibronectin therapy in sepsis and critical illness. AB - Plasma fibronectin may be an important component of host defense in critically ill patients, particularly after trauma and during sepsis. This paper reviews recent studies that have sought to characterize the natural history of plasma fibronectin during sepsis, as well as those studies that tested the effect of therapy with concentrated fibronectin in sepsis. The decrease in plasma fibronectin that generally is seen in humans during sepsis probably is due to many factors, and it has been difficult to produce a similar pattern in animal models. Depletion of plasma fibronectin is not a sensitive or specific predictor of imminent sepsis, and once sepsis is established, the concentration of plasma fibronectin is no more sensitive a predictor of mortality than are many other clinical markers. Early, uncontrolled trials of therapy with a fibronectin concentrate in patients with sepsis appeared to indicate a propitious effect on organ function. However, more recent controlled trials have failed to show a significant effect of therapy with fibronectin concentrate on either organ function or patient survival. PMID- 3326140 TI - [Avoidance of peptonic sulfamide antagonism and the testing of E. coli sensitivity to neoxazol]. PMID- 3326141 TI - [A nosological entity as yet unknown in Romania: adiaspiromycosis]. PMID- 3326142 TI - [Prof. Gheorghe Marinescu, an admirer of research in veterinary medicine in Romania]. PMID- 3326143 TI - Autoimmune conditions induced by epithelial solid tumors. PMID- 3326144 TI - Evaluation of CD5-positive B cells in blood and synovial fluid of patients with rheumatic diseases. AB - CD5 (OKT1, Leu-1) is an antigen originally associated only with T cells. This antigen has recently been detected on a population of B cells that have been implicated in autoimmune diseases, particularly in rheumatoid arthritis (RA). We determined the percentage of these cells in the peripheral blood (PB) and synovial fluid (SF) of patients with RA and other joint diseases (OJD) using flow cytometry and two-colour fluorescence. No significant difference was observed between the percentages of CD5-positive B cells in the PB of these two patient groups or healthy individuals. In comparison with PB, significantly higher percentages of these cells were observed in the SF of patients with RA, but not in SF of OJD patients. Higher percentages of B cells were also noted in RA SF. However, when B-cell percentages were accounted for, no significant difference was observed between the numbers of B cells expressing CD5 in SF. No correlation was observed between the percentages of CD5-positive B cells and the levels of rheumatoid factor (RF) or C-reactive protein (CRP). We conclude that CD5-positive B cells are an integral part of the B-cell pool of PB and that there is increased representation of B cells in SF. The increased percentages of B cells in RA SF, compared with OJD, may reflect the autoimmune phenomenon occurring in the rheumatoid joint. PMID- 3326145 TI - Pathogenetic aspects of organ-specific autoimmunity. AB - In the last few years a great deal of information on the etiopathogenetic aspects of organ-specific autoimmune diseases (OSADS) has been obtained. It has been shown that genetic factors play an etiologic fundamental role. They are responsible for the dysregulation of the immune system and for the target organ susceptibility which favour the onset of the diseases. Putative environmental factors, such as viral infections, can act as initiating or precipitating events only in genetically predisposed individuals. Immunological mechanisms capable of triggering autoimmune responses have been demonstrated. Data obtained from experimental models and from humans suggest that the ongoing expansion of autoreactive T cells with specificity for autoantigens (AAgs) can be considered as the main immunological event capable of inducing and maintaining the target organ damage. These cells can activate different effector systems, i.e., autoantibody (AAb)-producing B cells, cells with cytotoxic activity, etc., by releasing different combinations of lymphokines. In overt diseases AAbs are directly involved in the pathogenesis of lesions due to autoimmune responses against functional molecules and cellular receptors. The pathogenesis of the common inflammatory destructive lesions of the target organs is more complex and not yet clarified. A large proportion of T cells present in the inflammatory infiltrates are apparently not directed to the AAgs. Most cells display cytolytic activity and may contribute to tissue damage by releasing lymphokines which activate other cells and cascade the process. Vicious cycles, i.e., upregulation of class II and I molecules, alterations of the cytokine network, etc., are supposed to be involved in the maintenance of target organ lesions. PMID- 3326146 TI - [The abused child syndrome]. PMID- 3326147 TI - [Preventive medicine in primary care]. PMID- 3326148 TI - [Historiography of the development of immunology and comparative pathology in relation to anti-smallpox immunization and vaccination]. PMID- 3326149 TI - [Project for an automated data management system for the control of arterial hypertension]. PMID- 3326150 TI - [Problems of luxations and fractures of the mandible. A global summarizing overview]. AB - A general synthesis of the diagnostic and therapeutic problems related with the mandibular contusions, luxations and fractures is proposed. Emphasis is laid on the evolution of treatment methods, particularly on the various osteosynthesis developed for the last twenty years. PMID- 3326152 TI - [The role of macrophages in microorganism-host interactions]. PMID- 3326153 TI - [Metabolism of indolylacrylic acid. III. Effect of intestinal microbes on the excretion of indolylacryloylglycine in urine]. PMID- 3326151 TI - [Regression equations for calculating the volume of the left heart ventricle in children]. PMID- 3326154 TI - [Technic for processing salivary glands for scanning electron microscopy]. PMID- 3326156 TI - Papers dedicated to Paul O. Madsen on the occasion of his sixtieth birthday, July 26, 1987. PMID- 3326155 TI - [New etiopathogenic and therapeutic findings in bullous skin diseases]. PMID- 3326158 TI - Christian Fenger--another Danish surgeon in the Middle West. PMID- 3326157 TI - An experimental study of the treatment of bacterial epididymitis. AB - Two groups of rats were treated for epididymitis in an experimental study. The developing infection of E. coli was treated effectively by a single dose of cephalosporin in one group of rats. In the other group, where abscess formation had taken place, no effect of up to 9 days of treatment could be demonstrated, indicating the importance of early antibiotic treatment in bacterial epididymitis. PMID- 3326159 TI - Antimicrobials for the treatment of bacterial prostatitis. Historical developments and current trends. AB - The treatment of bacterial prostatitis has always been difficult since only few substances have proven effects in clinical practice. The reason for this was investigated by animal studies in two steps. First a model of experimental bacterial prostatitis was developed. Then pharmacological studies with determination of penetration of various antimicrobial substances into serum, interstitial fluid, urine and prostatic secretion were performed. As a result we could show, that the place of the inflammatory process is the interstitium with only little effects in the prostatic acini. Thus only substances with good concentration in the interstitium can be expected to be effective in the eradication of bacterial invasion of the prostate gland. These are the basic macrolide erythromycin for gram-positive germs, the amphoteric tetracyclines or the newest quinolones for gram-negative bacteria, mycoplasma or chlamydiae. PMID- 3326160 TI - Studies toward the subcortical pathogenesis of schizophrenia. AB - In addition to introducing the six articles joined by our thematic outlook, this article addresses the importance of subcortical structures as they may be related to information processing and the life experience of schizophrenic patients. This is a heuristic exercise aimed at bridging the conceptual gaps between clinical and research approaches to schizophrenia. A brief overview is then provided of current conceptualizations of a number of subcortical structures, each of which may play a part in the subcortical pathogenesis of schizophrenia in specific patients. The central concepts are failures in the "automaticity" with which prior experience may be recreated in parallel with current stimulus input in schizophrenia (with concomitant failures in future orientation or contextually generated expectancy), and the view of subcortical structures as constituting a "system" in which no single type of defect may be common to all schizophrenic patients. PMID- 3326161 TI - Role of the thalamus in language: is it related to schizophrenic thought disorder? AB - Crosson (1985) proposed a model for language production which integrated cortical with subcortical functions. The implications of this model for schizophrenia are explored. One conclusion is that neural systems, as opposed to a single neural focus, account for schizophrenic symptoms. In this light, data regarding dysfunction in the limbic system, nucleus accumbens, globus pallidus, and prefrontal cortex, which are often seen as contradictory, can be viewed as complementary. Another conclusion is that Crosson's model may have implications specific to schizophrenic thought disorder. Random triggering of semantic segments and inability to maintain contextual referents are discussed in the context of the language production theory. PMID- 3326162 TI - Orienting response research in schizophrenia: where we have come and where we might go. AB - This review and critique of orienting response (OR) research in schizophrenia examines the initial Western work, outlines current positions, and notes several areas in which further lines of research are needed. Discussion involves characteristics of schizophrenic patients who are OR nonresponders; OR nonresponding as a possible trait marker; the question of OR nonresponding in child patients; the association between negative symptoms and OR nonresponding as well as the possible existence of a specific subgroup marked by emotional withdrawal and cognitive disorganization; slow habituation as a prognostic index in high-risk children and adult acute patients; the need for research into defensive and startle responses as well as the OR, and possible interactions among them; electroencephalographic-autonomic differences in OR; and the need to explore the functional meaning of OR nonresponding in schizophrenia. PMID- 3326163 TI - Visual masking and the schizophrenia spectrum: interfacing clinical and experimental methods. AB - The present article reviews and evaluates 20 studies of susceptibility to visual masking among individuals within the schizophrenia spectrum using a neurophysiological framework provided by a multichannel model of masking. Particular emphasis is placed upon methodological considerations within the context of the current experimental visual masking literature. While there is ample evidence to suggest that individuals within the schizophrenia spectrum frequently exhibit a backward masking deficit, very little can be understood about the specific nature of the deficit. To gain increased understanding of the specific nature of this deficit, researchers need to use some contemporary theory of masking and derive a theoretical design rationale that facilitates a priori predictions in addition to the more typical post hoc theorizing. PMID- 3326164 TI - One more look at propranolol for the treatment of refractory schizophrenia. AB - Propranolol, a beta-adrenergic blocking agent, has been proposed previously as potentially useful in the treatment of certain otherwise treatment-unresponsive psychotic patients. This article reviews the published clinical trials of the efficacy of propranolol in schizophrenia to characterize those patients in whom it might be helpful and for whom future clinical trials should be designed. Despite a large number of inconsistent reports, the evidence to date favors its potential value as an adjunct to neuroleptic therapy in neuroleptic-resistant chronic schizophrenic patients. Several recommendations are made to improve the methodology of future clinical trials with this agent for the treatment of schizophrenia. PMID- 3326165 TI - Social functioning of schizophrenic patients: clinical and research issues. AB - Social dysfunction is generally considered an essential feature of schizophrenia. However, despite considerable interest in the social functioning of schizophrenic patients, the precise nature of the social deficits exhibited by these patients remains unspecified. No widely accepted criterion of social competence has been used to investigate their social functioning. Also, social skills researchers have often failed to recognize the heterogeneity of schizophrenia and the impact that this heterogeneity may have on attempts to implement psychosocial interventions. The adverse findings regarding the social behavior of schizophrenic patients are reviewed. Factors relating to schizophrenia that may affect their social functioning are discussed, as are directions for future research that may lead to more effective psychosocial interventions for schizophrenia. PMID- 3326166 TI - Evolution of veterinary anatomy teaching. PMID- 3326167 TI - [Gene technology and veterinary medicine. III. Transgenic animals: facts and perspectives]. PMID- 3326168 TI - [A modified Buhner suture for the elimination of vaginal prolapse in the cow]. PMID- 3326169 TI - Place cells in the brain: evidence for a cognitive map. PMID- 3326170 TI - Regulation of body weight and food intake. PMID- 3326172 TI - [Stress and immunity]. PMID- 3326171 TI - Molecular cloning and nucleotide sequence analysis of a transforming gene from human gastrocarcinoma cell line. AB - Mouse and rat fibroblasts were transfected with total DNA from human gastrocarcinoma cell line BGC-823. It was shown by hybridization assay that the genome of one of the rat secondary foci contains transforming genes from the human gastrocarcinoma cell line, which are homologous to the protooncogene c-Ha ras in the normal cells. The genomic library of the rat secondary foci was constructed, using lambda phage EMBL3 as the vector. The transforming gene Ha-ras of the human gastrocarcinoma cell was thus cloned by screening the library with the probes of human Alu repeat sequence and c-Ha-ras. The nucleotide sequences of the first and second exons were analysed by M13-dideoxy method. The result shows that the nucleotide sequence of the transforming gene is the same as that of the normal protooncogene except one nucleotide difference in the first exon. PMID- 3326173 TI - [The Soviet Red Cross and public health]. PMID- 3326174 TI - [Vladimir Il'ich Lenin and N. A. Semashko]. PMID- 3326175 TI - [Bolshevik physicians at the sources of Soviet public health]. PMID- 3326176 TI - [Foreign internationalists in the medical and health institutions of the Soviet Republic]. PMID- 3326177 TI - [Development of the epidemiological health service in Dagestan]. PMID- 3326178 TI - [Shaping of a health-oriented culture among the population of Bashkiria in the first decade of Soviet power]. PMID- 3326179 TI - [The Bolshevik physician R. S. Obraztsova]. PMID- 3326180 TI - [New material on Academician N. I. Grashchenkov]. PMID- 3326181 TI - [Candide in the land of health services research]. PMID- 3326183 TI - [Methodology and imaging contrast in shoulder arthrography]. PMID- 3326182 TI - [Non-ionic contrast medium (iopamidol) for esophagography in risk patients]. PMID- 3326184 TI - [Surgical treatment without prosthesis for aseptic bone necrosis of the femoral head]. PMID- 3326186 TI - [Polycystic kidney disease: recent developments]. PMID- 3326185 TI - Gonococcal endocarditis: a case report and review of the literature. AB - Despite the increasing incidence of gonococcal urethritis and cervicitis, endocarditis has become an infrequent consequence of infection with Neisseria gonorrhoeae. However, we recently had the opportunity to diagnose and treat a patient with this uncommon infection. He presented with febrile illness and a history of dysuria. After six days of incubation, cultures of blood yielded an isolate of N. gonorrhoeae. Treatment with penicillin plus streptomycin led to rapid resolution of the fever. Sequelae included left ventricular dilatation and aortic valve insufficiency. The latter was corrected by surgery. Our experience with this patient, as well as the 33 other cases reported in the literature since 1949, indicate that the diagnosis of gonococcal endocarditis should be suspected for any sexually active adult who presents with fever and a heart murmur. PMID- 3326187 TI - [Role of the basement membrane in the pathogenesis of polycystic kidney: a new pathogenetic hypothesis based on an experimental model]. PMID- 3326188 TI - [Treatment of urinary tract infection in the course of autosomal dominant polycystic kidney disease: new advances]. PMID- 3326189 TI - [Acquired cystic kidney dysplasia in the patient with chronic renal insufficiency]. PMID- 3326190 TI - [Patients with polycystic kidney in hemodialysis therapy and candidates for kidney transplantation]. PMID- 3326191 TI - [Lectin histochemistry in the study of the renal tubule, with special reference to the developmental phases of rejection]. PMID- 3326192 TI - [Immunoenzymatic study of the peripheral blood and bone marrow in chronic lymphatic leukemia]. PMID- 3326193 TI - [Myelodysplastic syndromes as preleukemic states]. PMID- 3326194 TI - [Foreign bodies in the esophagus]. PMID- 3326195 TI - [We congratulate--Ulleval across 100 years]. PMID- 3326196 TI - [Norwegian Nurses' Association exists 75 years: festive anniversary day in Oslo City Hall]. PMID- 3326197 TI - [This is my fondest memory: with a rescue ship to the hospital in a full-blown gale]. PMID- 3326198 TI - [Sports from a preventive medicine perspective]. PMID- 3326199 TI - [Types of training and their effects on muscle structure]. PMID- 3326200 TI - [Diagnosis and prevention of muscular imbalances]. PMID- 3326202 TI - [Inventory of presumed ergogenic dietary supplements]. PMID- 3326201 TI - [Sports and the child]. PMID- 3326203 TI - Effect of Sensit (fendiline) in the light of new data. PMID- 3326204 TI - In memoriam Adam Politzer. PMID- 3326205 TI - Development of modern European schools of ophthalmology. PMID- 3326206 TI - Dementias: recent experimental evidence and clinical perspectives. PMID- 3326207 TI - Observations with intensive Mydocalm treatment in neurological cases. PMID- 3326208 TI - Treatment of hypertension. Starting treatment, gradualness, effectivity and individualization. PMID- 3326209 TI - Observations with Viskaldix, a combined antihypertensive agent. PMID- 3326210 TI - On generalised septic vessel diseases. By Friedrich Wegener, 1937 (translation) PMID- 3326211 TI - Wegener and Wegener's granulomatosis. PMID- 3326214 TI - [Articles from then and now. The first Dutch female veterinarian, 1931]. PMID- 3326212 TI - Failure of aerosolised 99mTc DTPA clearance to predict outcome in patients with adult respiratory distress syndrome. AB - The rate of clearance of technetium-99m labelled diethylene triamine pentacetic acid (99mTc DTPA) was measured in 32 patients with adult respiratory distress syndrome to determine if a more rapid clearance rate, possibly reflecting a more severe abnormality of pulmonary function, was associated with a reduced likelihood of recovery from pulmonary failure. Although the mean rate of clearance from lung to blood (T1/2LB) of 99mTc DTPA was more rapid in the patients (T1/2LB = 29 (SEM 3.2) min than in 42 normal subjects (T1/2LB = 59 (1.8)min), there was no difference between the clearance rate in the 18 patients who recovered from respiratory failure (T1/2LB = 31 (5) min) and the 14 who died (T1/2LB = 27 (4) min). Additionally, not all patients studied had abnormally rapid clearance rates. In 12 of the 32 patients the T1/2 fell within the range for normal individuals; this was found more commonly in patients who were predisposed to develop adult respiratory distress syndrome by pancreatitis or massive blood transfusion. These data suggest that a single measurement of 99mTc DTPA clearance in patients with established respiratory failure and adult respiratory distress syndrome is of no value in assessing the likelihood of recovery from this condition. PMID- 3326215 TI - [The female veterinarian: then and now]. AB - The position of the female student in Europe and the USA in the past, both in veterinary medicine and in other disciplines, is discussed. On the other hand the present situation is described. The first female veterinarian in the Netherlands was Jeanette Voet, who graduated in 1930. Of the Faculty of Veterinary Medicine in Utrecht 1403 students are currently enrolled, 628 of them being females. In 1987, 70 per cent of the first-year undergraduates are females. The functions of female veterinarians who graduated are reviewed. PMID- 3326213 TI - Enteric coated microspheres of pancreatin in the treatment of cystic fibrosis: comparison with a standard enteric coated preparation. AB - In an open, randomised crossover study enteric coated microspheres of pancreatin were compared with a standard preparation of enteric coated pancreatin over two consecutive 28 day treatment periods in 23 adults with steatorrhoea due to cystic fibrosis. Lipase intake was equal to the patients' previous requirements and was the same during the two months. Patients performed 72 hour faecal collections at the end of each month and completed diary cards daily throughout. Comparison of the month of treatment with enteric coated microspheres with the month of standard enteric coated tablets showed a significant increase in body weight on microsphere capsules (p less than 0.02). There was also a reduced frequency of bowel actions (p less than 0.001) and abdominal pain (p less than 0.05), and improvement in stool character (p less than 0.001) on microsphere capsules. Faecal fat excretion was reduced by 44% with the microsphere capsules (p less than 0.01), and 86% of patients showed an increased coefficient of fat absorption (mean increase 13%, 95% confidence limits 6.5-19.1%; p less than 0.001). Eighty one per cent of patients preferred microsphere capsules of the two treatments. Thus enteric coated microsphere capsules are more effective in treating steatorrhoea in cystic fibrosis than standard enteric coated tablets. PMID- 3326216 TI - HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease. AB - Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP incompatible BM, but in none of five recipients of DP-compatible BM. This difference was highly significant (p less than 0.001, Fisher's exact test). Moreover, severe acute GVHD was significantly increased in recipients of haploidentical, DR compatible, but DP incompatible BM as compared to severe acute GVHD in 88 recipients of HLA identical BM (p less than 0.0001). In contrast, there was no difference in acute GVHD between recipients of haploidentical, DR and DP compatible BM and recipients of HLA-identical BM. The data presented here provide strong evidence for the first time that HLA-DP antigens play a role as transplantation antigens. PMID- 3326217 TI - Inhibition by the mushroom toxins alpha-amanitin and phalloidin of hepatopoietin induced 3H-thymidine incorporation into rat liver DNA and of plasma protein production in hepatocyte cultures. AB - In primary cultures of rat hepatocytes the induction of 3H-thymidine uptake into DNA of liver cells by the liver cell proliferation factor hepatopoietin demonstrates that this factor is active not only in vivo but also in vitro. Addition of the mushroom toxins alpha-amanitin or phalloidin to liver cell culture decreased the uptake of 3H-thymidine into hepatocytes (in the absence or presence of hepatopoietin) as well as the attachment of the hepatocyte cultures. Mushroom toxins also inhibited the production of plasma proteins in hepatocyte cultures. The inhibition, observed at toxin concentrations from 10(-5) to 10(-7) M, was dose-dependent. At low concentrations of phalloidin the inhibition appears to be selective for certain proteins. PMID- 3326219 TI - [Arterialization of bone grafts of the mandible in an experiment]. PMID- 3326218 TI - [New method of treating progenia by longitudinal ostectomy of the mandibular rami with bone autoplasty]. PMID- 3326220 TI - [Development of pins for artificial teeth and of a reinforcing element for filling materials]. PMID- 3326222 TI - John Chalmers DaCosta, M.D. PMID- 3326221 TI - [Determination of mucosal overload areas of the prosthetic bed following fixation of a removal denture]. PMID- 3326223 TI - Insanity: evolution of a medicolegal concept. PMID- 3326224 TI - Victor Robinson, M.D. (1886-1947): a centennial tribute to a pioneer medical historian. PMID- 3326226 TI - Remarks made at the rededication of the grave site of Dr. Benjamin Rush, Christ Church Cemetery, Fifth and Arch Streets, Philadelphia, Pennsylvania, Sunday, April 26, 1987. PMID- 3326225 TI - Science and medicine in the social construction of woman: from Aristotle to the corpus callosum. PMID- 3326227 TI - Sketch of Dr. Benjamin Rush. PMID- 3326228 TI - The bicentennial of the College of Physicians of Philadelphia. PMID- 3326229 TI - Julian Johnson 1906-1987. PMID- 3326230 TI - The Blockley politician. By John C. DaCosta, 1931. PMID- 3326231 TI - [The 70th anniversary of the October Revolution and the science of cytology in the USSR]. PMID- 3326233 TI - [Non-insulin-dependent diabetes in obesity (type IIB): study of insulin secretion, insulin receptors and response to low-calorie diet]. PMID- 3326232 TI - [Dependence of the proliferation of cell line 3T6 on a totally serum-free medium on epidermal growth factor]. AB - The Eagle medium containing the epidermal growth factor (EGF), insulin, transferrin and a source of iron is able to support proliferation of 3T6 cells in the absence of serum. The formation of 3T6 cell clones in the similar medium supplemented with non-essential amino acids confirms the usefulness of such a medium for cell cultivation. It has been found that the exclusion of EGF rather than other above components from the medium inhibits most highly the increase in cell number. PMID- 3326234 TI - [Characteristics of the etiology, pathogenesis, clinical course and treatment of various forms of acute infectious diseases of the kidneys]. PMID- 3326235 TI - [Treatment of hypospadias in children]. PMID- 3326236 TI - [Diagnosis and treatment of arterial hypertension in patients with terminal stage of chronic renal failure and after transplantation of the kidney]. PMID- 3326237 TI - [Neurophysiological diagnosis of neurogenic bladder]. PMID- 3326239 TI - The nubbin sign on computed tomography and sonography. AB - The loss of parenchyma in the lower pole of a kidney with a duplicated collecting system may mimic a mass on urography ("the nubbin sign"). Computed tomographic findings of this entity are diagnostic. The diagnosis may be difficult to make using sonography alone. PMID- 3326238 TI - [Etiology and pathogenesis of ovarian varicocele]. PMID- 3326240 TI - CT demonstration of extension of renal angiomyolipoma into the inferior vena cava in a patient with tuberous sclerosis. AB - The authors present a case of tumor thrombus in the inferior vena cava produced by angiomyolipoma in a young woman with tuberous sclerosis. Diagnosis was made by computed tomography (CT) by measuring the attenuation values of the tumor thrombus. The values obtained were characteristic of fat, demonstrating that tumoral invasion was the cause of the thrombus. To our knowledge, this is the first description of such an association shown by CT in the literature. PMID- 3326241 TI - Calcified ganglioneuroma of the bladder. AB - Ganglioneuromas involving the genitourinary tract are extremely rare but are potentially serious tumors. We describe a patient, known to have von Recklinghausen's disease, who presented with a calcified ganglioneuroma of the bladder demonstrated by intravenous urography, sonography, and computed tomography. PMID- 3326242 TI - Bladder hemangioma: ultrasonographic demonstration. AB - We report a child with bladder hemangioma, which is a very rare benign vascular tumor. Postvoid excretory urography and ultrasound of the bladder demonstrated the lesions. The merits and demerits of various imaging modalities and the possible role of computed tomography (CT) and magnetic resonance imaging (MRI) are also discussed. PMID- 3326243 TI - [Achievements and prospects of the development of pediatric otorhinolaryngology]. PMID- 3326244 TI - Potential arthropod vectors of African swine fever virus in North America and the Caribbean basin. AB - In an effort to identify arthropods that might serve as vectors and perhaps reservoirs of African swine fever virus (ASFV) if it were to enter the U.S.A., the blood-sucking insect Triatoma gerstaeckeri and four species of ticks of the genus Ornithodoros were established in colonies capable of reproducing in numbers sufficient to enable thorough studies to be made of their ASFV vector potentials. A nymphal stage of T. gerstaeckeri carried the virus for 41 days and retained it through one molt, but was unable to transmit it to susceptible pigs. Studies on O. coriaceus revealed that the species is able to harbor and transmit the virus for greater than 440 days, passing it trans-stadially from the first nymphal stage to the adult, sustaining it through at least four molts. Trans-ovarial passage was not demonstrated and nearly 40% of the ticks died, apparently, of the ASFV infection. O. turicata collected in Florida was also found to be capable of becoming infected with ASFV and transmitting it by bite to susceptible pigs. O. puertoricensis collected during the ASF eradication programs in the Dominican Republic and Haiti was not only readily infected experimentally, but it was also able to transmit the virus trans-stadially and trans-ovarially. However, ASFV was not isolated from any of the 350 O. puertoricensis collected in the Dominican Republic and Haiti. O. parkeri from a long-established laboratory colony were able to carry the virus through at least one molt, but they were unable to transmit it to susceptible pigs. PMID- 3326245 TI - Binding of fibronectin to Escherichia coli isolated from bovine mastitis from different geographical regions. AB - Seventy strains of Escherichia coli, isolated from bovine mastitis in Australia, Denmark, Norway and the U.S.A., were tested for their ability to bind fibronectin. Fifty-three strains (76%) interacted with iodinated fibronectin at a level exceeding 5% of the total radioactivity added. Binding of the amino terminal (29 kD) fragment of fibronectin was tested for 15 strains, and 6 strains (40%) bound greater than 5%. Bacteria binding the 29 kD fragment at greater than or equal to 19% of the added protein, consistently showed "high" attachment to bovine skin fibroblasts. These cells were shown by immunofluorescence to produce extracellular matrix containing fibronectin. Strains binding lower amounts of fibronectin or 29 kD fragment adhered poorly to these fibroblasts. PMID- 3326246 TI - Cytotoxins in non-enterotoxigenic strains of Escherichia coli isolated from feces of diarrheic calves. AB - We have examined the cytotoxic responses produced in HeLa and Vero cell cultures by sonicates from 15 non-enterotoxigenic (STa-, LT-) strains of E. coli, highly lethal for mice parenterally LD50 less than 3 X 10(7) CFU), which had been isolated from feces of diarrheic calves. Three types of cytotoxic responses were observed. Type 1 (five strains) consisted of enlargement, rounding and polynucleation of HeLa cells, an effect previously reported with cytotoxic necrotizing factor (CNF) in E. coli from infant and piglet enteritis. Type 2 toxicity (three strains and the control Vir strain S5) was also characterized by enlargement and polynucleation of HeLa cells, but in contrast to Type 2 effect, cells were elongated. Sonicates from the latter strains were lethal for chickens, producing the lesions previously described with Vir strains. Type 3 toxicity (two strains and the control VT strain H19), produced an extensive destruction of both Vero and HeLa cell cultures. Cytotoxic effects were completely abolished upon heating for 1 h at 60 degrees C for Type 1 and 2 extracts and at 80 degrees C for Type 3 extracts. Seroneutralization assays showed that cytotoxins of the same type were closely related antigenically. In addition, a slight cross neutralization was observed between Type 1 (CNF) and Type 2 (Vir) toxins. PMID- 3326247 TI - Possible relationship of proliferative enteritis in pigs and hamsters. AB - Three- to six-week-old hamsters were orally inoculated with broths containing one of the following cultures: Campylobacter mucosalis; C. hyointestinalis; C. coli; C. jejuni, all of porcine proliferative enteritis origin, or else C. jejuni of hamster origin. Hamsters given the last of those organisms were shown to have colonisation of their intestines by C. jejuni and 36 of 40 developed an acute enteritis. Mild hyperplasia of enterocytes in ileal crypts was evident in one hamster 2 days after it was given C. coli. No other lesions were detected. Further 3-week-old hamsters were orally inoculated with homogenised intestinal mucosa collected from 4 pigs (A-D) affected by proliferative enteritis. Lesions of proliferative enteritis were detected in 7 of 41 hamsters necropsied 10-21 days after being dosed with mucosas B or D. Marked hyperplasia of ileal enterocytes, associated with numerous intracellular Campylobacter-like organisms, were invariably detected in experimentally affected hamsters. No particular Campylobacter sp. was consistently isolated. None of the controls had demonstrable lesions. The results suggested that cross-species transmission of proliferative enteritis was possible from pigs to hamsters. Therefore a common initiating or aetiological agent may be present. No specific organism was identified as filling this role by inoculation of hamsters with pure cultures. PMID- 3326248 TI - Preparation and characterisation of envelope proteins from Haemophilus pleuropneumoniae. AB - Envelope proteins of Haemophilus pleuropneumoniae were extracted by 3 methods and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE). Three major envelope proteins (45,000 Mr, 41,000 Mr, 31,500 Mr) were distinguished in sonicated cell envelopes together with minor proteins. Using selective solubilisation with sodium lauryl sarcosinate or Triton X-100, outer membrane proteins were distinguished from those of the cytoplasmic membrane. Extraction into LiCl produced a similar profile, but the 41,000 Mr and 31,500 Mr bands were present in reduced amounts. Extraction into saline at 60 degrees C produced a grossly different pattern, with a major band at 20,000 Mr. All 3 major envelope proteins were shown to be heat-modifiable, and the 31,500 Mr band was found to be the non-heat-modified form of a 43,000 Mr protein, which showed similar properties to the Protein d of H. influenzae which is related to the OmpA protein of E. coli K-12. The 45,000 Mr major protein was also weakly associated with the peptidoglycan in SDS/Triton at low temperature. PMID- 3326249 TI - [Experiments to identify Mycoplasma isolates from cell cultures]. AB - Identified were various species of Mycoplasma organisms isolated from three continuous cell lines--BHK-21, SPZF, and TT. On the base of cultural, biochemical, and serological investigations the isolates were defined as M. bovirhinis, M. arginini, and A. laidlawii. The bovine sera, used to culture the cell lines were shown to be the basic source of contamination with Mycoplasma organisms. This made it necessary to carry out a preliminary study on each batch of serum for Mycoplasma contamination prior to its use for laboratory and productional needs. PMID- 3326250 TI - [Survival of pathogenic microorganisms in the Black Sea mussel with an experimental infection]. AB - The survival rate was followed up of S. typhimurium, S. enteritidis, S. aureus, and E. coli in the organs of M. galloprovincialis L. in experimental conditions. A vat was used with 30 mussels in 10 l of sea water contaminated with 10 cm3 broth culture in conc. of 2.10(4) bacterial cells per cub. cm. The water was changed at 24-hour intervals. Microbiologic studies were carried out of the gills, liver, and meat of the mussels and of the sampled sea water. Lowest survival rate showed S. aureus--up to the second day, S. typhimurium and S. orientalis--up to the 4th days (in the gills only), and E. coli--up to the sixth day (in the gills and liver). None of the experimental strains to the sixth day (in the gills and liver). None of the experimental strains was isolated from the meat. With regard to the periods of investigation cited M. galloprovincialis L. could play the role of a carrier, resp. vector of the infection and could bring about a disease after consumption. Stated is the important part played by mussels as biofilter, and, at the same time, as source of pathogenic bacterial microflora. PMID- 3326252 TI - [Homage to the Pasteur Institute of Paris]. PMID- 3326253 TI - [The 70th anniversary of the Great October Socialist Revolution and our health services]. PMID- 3326254 TI - [Jan Evangelista Purkinje. 200 years' since the birth of the Czech genius]. PMID- 3326251 TI - 75 years since the publication of the "Traite de la Rage" by Victor Babes. PMID- 3326255 TI - [The diabetic in the inpatient internal medicine department]. PMID- 3326256 TI - [Insulin dosage in Czechoslovakia (on the question of insulin utilization)]. PMID- 3326257 TI - [Training and development of military personnel in medical colleges]. PMID- 3326258 TI - [Organization of the medical support for Soviet troops in the Stalingrad offensive operation (on the 45th anniversary of the Battle of Stalingrad)]. PMID- 3326259 TI - [Characteristics of the medical support for the 64th Army during the destruction of the encircled enemy troops at Stalingrad]. PMID- 3326260 TI - [Ultrasonic diagnosis of joint diseases and injuries]. PMID- 3326262 TI - [The medical service of the Red Army during the civil war and the first postwar years]. PMID- 3326261 TI - [Surgical treatment of ptosis using a silicone suture]. PMID- 3326263 TI - [Medical and materiel-housing support for military servicewomen during World War II]. PMID- 3326264 TI - [Effectors of energy metabolism]. PMID- 3326265 TI - [Present-day status of an old concept (vegetarianism)]. PMID- 3326266 TI - [Radioactive iodine isotopes in food products]. PMID- 3326267 TI - Clinical use of antithrombin III concentrates. AB - The biochemical and biological properties of antithrombin III (AT III) and the clinical consequences of a deficiency of this inhibitor are described. Therapy with concentrates of purified AT III has been carried out for about 10 years and the present experience is reviewed. In a relatively small number of patients with congenital AT III deficiency it is necessary, under certain condition to substitute AT III. A considerably more frequent use of AT III concentrates has been made in acquired AT III deficiency, especially in shock and diffuse intravascular coagulation (DIC). This therapy was shown to be promising since the duration of DIC could be considerably shortened and the frequency of fatal events could be significantly diminished. No undesirable side effects of substitution with virus-sterilized AT III concentrates have been hitherto observed. PMID- 3326268 TI - A simple method to obtain low density marrow cells for human marrow transplantation. AB - Removal of more than 99% of the erythrocytes and 74% of the nucleated cells from marrow grafts was achieved by density floatation separation in Percoll gradients with a density of 1.070 g/ml in eight 250-ml tubes, containing up to 3 X 10(9) nucleated cells per gradient. More than 90% of the myeloid and erythroid progenitor cells were recovered in the low density fraction. It appeared mandatory to use a centrifuge with the possibility of a gradual acceleration and deceleration. Twenty-five patients received a marrow graft from a histocompatible sibling after additional lymphocyte depletion by counterflow centrifugation, and 5 patients with T lymphoblastic malignancies received an autograft after in vitro purging with immunotoxins. All evaluable patients engrafted within normal limits, except 1 patient with an autoimmune pancytopenia who responded to steroids and 1 patient with a CMV infection. Four patients died too early for complete evaluation. The described separation method is easy, cheap and requires only 2 h for the complete processing of a marrow graft. PMID- 3326269 TI - Detection of the human erythrocyte surface antigen gerbich by flow cytometry using human antibodies and phycoerythrin for extreme immunofluorescence sensitivity. AB - We used indirect immunofluorescence and flow cytometry to detect the human erythrocyte surface antigen Gerbich. The procedure consisted of sequential erythrocyte-labeling with human antibody to Gerbich, biotinylated goat anti-human IgG and finally phycoerythrin-conjugated streptavidin. With maximal excitation of phycoerythrin at 546 nm, an increase in the fluorescence sensitivity was achieved. All erythrocytes from normal controls had detectable Gerbich antigen with little variation in antigen density between individuals. Six Gerbich negative patients had no detectable antigen. By diluting the erythrocytes, as few as 0.1% antigen-positive cells in an antigen-negative population could be detected. These studies indicate that flow cytometry is a useful technique for the detection of erythrocyte surface antigens. PMID- 3326270 TI - [Lev Vasil'evich Gromashevskii (on the centenary of his birth)]. PMID- 3326271 TI - [On the 50th anniversary of the Chair of Tuberculosis at the Kiev Medical Institute]. PMID- 3326272 TI - [Levels of cortisol, immunoreactive insulin and somatotropic hormone in the blood of patients with chronic ischemic heart disease]. PMID- 3326273 TI - [Plant preparations in the complex therapy of patients with diabetes mellitus (review of the literature)]. PMID- 3326274 TI - [Broncholytic efficacy of berotec and spontaneous respiration with positive end expiratory pressure]. PMID- 3326275 TI - [Effect of the medicinal form and routes of administration of drugs on their pharmacokinetics and biological availability (review of the literature)]. PMID- 3326276 TI - [Monoclonal antibodies--their clinical and diagnostic importance]. PMID- 3326277 TI - [A case of spontaneous pneumoperitoneum in a female patient with pneumatosis cystoides intestinalis]. AB - A case of a woman with spontaneous pneumoperitoneum as result of pneumatosis cystoides intestinalis is reported. A brief review of this rare disease and its pathogenetic mechanisms is presented. The clinical course of the pneumatosis cystoides intestinalis was characterized by abdominal pain and distention, vomiting. The disease was proved by contrast X-ray examination. The pneumoperitoneum was the result of subserous cyst rupture and had a benign course. It was treated successfully with chemotherapeutics. The participation of extensive bacterial growth in the pathogenesis of the pneumoperitoneum is discussed. PMID- 3326278 TI - [Polyunsaturated fatty acids, hyperlipidemia and atherosclerosis]. PMID- 3326279 TI - [The echographic histogram--its use in the diagnosis of diffuse liver diseases]. AB - Quantitative evaluation of the echographic findings in patients with chronic liver diseases was carried out. 64 persons were examined--15 patients with liver steatosis, 21 patients with chronic hepatitis, 17 patients with liver cirrhosis and 15 healthy persons as controls. The diagnosis in all patients was confirmed by liver biopsy. With the help of the computer device of the echograph and by the same experimental conditions were measured: the mean echogenicity of a certain area (in units of density), the most frequent echogenicity and the maximal number of points with most frequent echogenicity. The analysis of the results showed that ultrasound examination allows the differentiation from the normal liver structure of the diffuse liver lesions (echogenicity above 20) and of liver steatosis (echogenicity above 26). The echographic histogram cannot differentiate chronic hepatitis from liver cirrhosis. This is possible by other echographic criteria. PMID- 3326280 TI - [Insulin secretion and action in acromegaly]. AB - 17 patients with active acromegaly (7 of them had diabetes mellitus, too), 13 patients with type I diabetes mellitus and 20 healthy controls were examined. The residual beta-cell secretion was determined by venous Tolbutamide test and the insulin sensitivity was determined by euglycemic clamp-technique. A positive correlation was found between the growth hormone level and prolactin and the size of the basic insulin secretion. In acromegaly (with or without diabetes) the sensitivity of beta-cell apparatus towards the stimulant Tolbutamide is preserved but the insulin reserves are diminished. There exists a positive correlation between the growth hormone level and the degree of insulin resistance and between the increased prolactin level and the degree of insulin resistance in acromegalic patients. PMID- 3326281 TI - [Modern diagnostic tests to determine nonspecific bronchial hyperreactivity in bronchial asthma patients]. PMID- 3326282 TI - [Diagnostic potentials of echography in renal vein thrombosis]. AB - The authors have followed up by ultrasound two cases of secondary thrombosis of the left renal vein in patients with chronic aggravated glomerulonephritis with nephrotic syndrome and present the echographic findings in the acute stage as well as in the reverse course of the disease. The purposeful ultrasound examination is recommended in patients with nephrotic syndrome for the discovery of the secondary thrombosis of the renal vein which is rarely diagnosed. PMID- 3326283 TI - [Experimental infection and immunity of enteroinvasive Escherichia coli in the cornea of guinea pigs]. PMID- 3326284 TI - Splenic metastases in ovarian carcinoma. PMID- 3326285 TI - [Effect of captopril on plasma renin activity and blood aldosterone in patients with chronic pyelonephritis and urinary tract infection]. PMID- 3326286 TI - [Treatment of hypertension using converting enzyme inhibitors]. PMID- 3326288 TI - [Axel Munthe, physician and writer]. PMID- 3326287 TI - [Plasma inhibitors of interleukin 2 in normal conditions and in pathological states]. PMID- 3326289 TI - [Localization of adrenal tumors]. AB - The application of newly developed methods to localization of adrenal tumours has improved diagnostic accuracy, yet the challenge still exists. The sensitivity of ultrasound is too low for imaging small adrenal tumours, thus reducing sonography to a screening method. Computed tomography is a fast and sensitive localizing method, even for small tumours, with a low radiation exposure. Endocrine-active tumours with high hormone-secreting activity or displaying a tendency to additional extra-adrenal presentation will generally be best localized by scintigraphic imaging. Sonography and computed tomography as non-invasive methods and invasive puncture of the tumour or of the cyst with consequent cytological examination of the obtained material are most important procedures in the diagnosis of endocrine-inactive adrenal masses. PMID- 3326290 TI - [Use of sonography at the peripheral hospital in the diagnosis of kidney tumors]. AB - 33 kidney tumours were detected in 15,500 routine scans of the upper abdomen. 13.7 per cent of these tumours were asymptomatic at the time of diagnosis. The size of these accidentally detected tumours was evidently smaller than in the case of symptomatic ones and the patients were younger at the time of diagnosis. The diagnosis was falsely positive in one case and falsely negative in 3 cases. In 2 cases of incorrect negative findings the sonographic diagnosis was hydronephrosis, but IVP and cytology of the specimen proved that these tumours were urothelial carcinomas. Apparently the weak point in sonographic diagnosis is the diagnosis of urothelial carcinomas. In cases of suspected kidney tumour or a sonographic diagnosis of hydronephrosis additional diagnostic methods must be undertaken. Our results show that adequate and cost-effective diagnostic information in the detection of kidney tumours is obtained in the majority of cases by sonography and urography. PMID- 3326291 TI - [Forensic medicine aspects of resuscitation]. AB - Nowadays, in almost all cases of clinical death, there is at least a remote chance of resuscitation, of restoring breathing and circulation by means of modern methods of cardiopulmonary resuscitation. Statistically, there are more cases of cardiocirculatory arrest due to an internal cause than to a traumatic cause. Just as medical activity in general, resuscitation is increasingly discussed in its legal and ethical aspects. The duty to exercise due care and proper qualification require a very specific approach in the case of resuscitation, as the chain of persons potentially involved in life saving stretches from the medical layman to the specialist trained to deal with emergency situations. As opposed to conditions in other countries, in Austria the duty to render aid and assistance as statutory provision of the penal code can be of great importance in such cases. Criteria and definition, especially in the ad hoc establishment of death, assume a special significance in resuscitation. Over the past years, resuscitation measures within the complex of the procurement of death have repeatedly been put up for discussion. Examples from US judicature may help to define the problem more clearly and also to offer solutions for similar cases. Such decisions should essentially be guided by the consideration of the presumed will of the patient who no longer is in a position to exercise the right of self-determination. PMID- 3326292 TI - [Neomysticism in medicine. The example of homeopathy]. AB - The revival of neomysticism, especially promoted by nonqualified representatives of press and tv, leads to a worldwide trend to homoeopathy, acupuncture, herb cure, Christian-Science, and to many others. According to the comprehensive publications of Prokop, the successful treatment by paramedical methods are due to placebo and self-healing. The statements of paramedical representatives will be accepted by the public, if representatives of science do not offer adequate criticism. Successful healing by any kind of treatment--e.g. of disturbances of well-being--is well established. Representatives of paramedicine applying "mystical treatment" to humans are obliged with necessity to explain success as "mysticism". In any case it is unwise to use the basis of natural science to explain mystic phenomena, as the representative of paramedicine--and occasionally a "mystic-oriented" representative of natural science--proves his lack of sound judgement. PMID- 3326294 TI - [Contraindications and complications in vaccinations]. AB - By immunizations many infectious diseases and their associated severe complications can be prevented. The high importance of vaccinations must be emphasized by the paediatricians. But it is also very important to know the contraindications and especially the rare complications and also adverse reactions following some immunizations e.g. against pertussis, tuberculosis, measles, rubella, diphtheria, tetanus and polio, which must be carefully investigated. The contraindications to immunizations must be paid attention, but they should not be dramatized. Slight adverse reactions following some immunizations some hours or days later may not be considered as complications (e.g. some children develop fever, become restless or have a broken sleep in the following night; reddening at the place of injection, a transitory exanthem and others). Incomplete knowledges and informations in side of some physicians must be removed by permanent graduate medical education. PMID- 3326293 TI - [Heavy metal and trace element deviations. A comparison of idiopathic dilated cardiomyopathy and coronary heart disease]. AB - Blood, serum and urine (24-hour-samples) concentrations of cadmium, zinc, calcium and magnesium were determined by means of atomic absorption spectrophotometry in 60 patients, therefrom 30 patients with idiopathic dilated cardiomyopathy (IDC) and 30 patients with coronary heart disease (CHD). The data of heavy metal and trace element concentrations of IDC and CHD patients were compared with each other and furthermore, for each group separately, correlated with patients history data, laboratory evaluations and data from heart catherization protocol. IDC patients showed higher blood cadmium concentrations (p less than 0.001) and lower serum zinc concentrations (p less than 0.001) compared to CHD patients. Serum levels of calcium and magnesium were not different in both groups. In urine samples IDC patients had lower concentrations of calcium (p less than 0.01) and magnesium (p less than 0.01) compared to CHD patients. Urine concentrations of cadmium and zinc were in the same range in both groups. The comparison of heavy metal and trace element concentrations with clinical data did not reveal definite correlations, however, data from experimental studies pointing out interactions of heavy metals and trace elements, could serve as useful interpretations. Hypomagnesemia in both patient groups (IDC, CHD) requires clinical follow up and substitution treatment. PMID- 3326295 TI - [Comparative review of various resuscitation procedures]. AB - During the last 10 years many experiments have confirmed the theory that blood flow during CPR likely occurs as a result of manipulation of intrathoracic pressure. In order to improve vital organ perfusion by increasing intrathoracic pressure many different techniques of CPR have been developed. These include "new CPR" (simultaneous ventilation and compression), asynchronous ventilation, prolonged compression, and continuous or interposed abdominal compression. Other methods like open chest CPR and the use of mechanized CPR or even cardiopulmonary bypass have also recently been proposed. All these techniques are reviewed in detail. PMID- 3326296 TI - [Drug use and ionizing radiation in early pregnancy. Risk assessment and postpartum results]. AB - The influence of medical drugs and X-rays upon early pregnancy causes problems of great responsibility for the physician. He is supposed to grant optimum consultation to the anxious women who finally have to decide to carry on their pregnancy or not. This topic is difficult to value as controlled prospective studies are not practicable for ethical reasons, and the results of animal experiments are rarely transferable to human medicine. In this paper the facts and data of our consulting activities are summarized from April 1985 to May 1986 in the sense of a prospective study. Over all 64 consultations were performed in these 14 months, up to now 30 women have been delivered of a newborn. The procedure and the principles of our consultations and the postnatal results are presented below. PMID- 3326297 TI - [Pathologic enzyme patterns in sonographically verified liver metastases]. AB - The serum enzyme pattern, consisting of GOT, GPT, lactate dehydrogenase, gamma glutamyl transpeptidase and alkaline phosphatase, was investigated in 128 patients with sonographically verified liver metastases. Gamma glutamyl transpeptidase and alkaline phosphatase turned out to be the most sensitive enzymes, being elevated in 89% and 88%, respectively. The GOT was elevated in 45% GPT in 37.5% and lactate dehydrogenase in 56% of all cases. The enzyme elevation did not correlate with the degree of liver involvement. In conclusion, pathological serum enzyme patterns are useful for the detection and follow up of liver metastases. Normal serum enzyme levels do not rule out the presence of liver metastases. PMID- 3326298 TI - The elimination of furazolidone and its open-chain cyano-derivative from adult swine. AB - 1. A sensitive method for the determination of 3-(4-cyano-2-oxobutylidene amino) 2-oxazolidone, the open-chain cyano-derivative of the veterinary drug furazolidone, in swine plasma and tissues is described. 2. After dosing adult swine orally with furazolidone (690 mg/animal per day) for 10 days no furazolidone was detected in liver, kidney and muscle (less than 2 ng/g). The half life of furazolidone as measured from the terminal phase of the plasma curves was 45 minutes. In urine, small amounts (less than 0.3% of total dose) of furazolidone were detected. 3. In contrast to other animals, 3-(4-cyano-2 oxobutylidene amino)-2-oxazolidone is a minor metabolite in swine with a plasma half life of 4 h. No cyano-derivative was detected in liver and kidney (less than 5 ng/g) 2 h after the last administration of furazolidone; 24 h after the last administration, the concentration in plasma was less than 2 ng/ml and in muscle less than 5/g. 4. The cyano-derivative was not mutagenic in the Salmonella/microsome test, with or without metabolic activation. PMID- 3326300 TI - Computed tomographic mammography in the diagnosis of breast diseases. PMID- 3326299 TI - A review of the methods of chemical synthesis of sulphate and glucuronide conjugates. AB - 1. Methods for the synthesis of drug conjugates with sulphuric acid have been reviewed. 2. Some analytical methods are presented for the analysis of sulphate conjugates. 3. The synthesis of several types of N, O and C beta-D-glucuronides is reviewed. Different beta-coupling reactions of protected glucuronides are presented. 4. Application of n.m.r. and mass spectrometry to the analysis of beta D-glucuronides is discussed. PMID- 3326301 TI - [Bernard Langenbeck as a teacher of physiology and pathologic anatomy in Gottingen]. PMID- 3326302 TI - [Nosologic aspects and trends in the science of schizophrenia]. PMID- 3326303 TI - [A historical digression on the development of the specialist in public health]. PMID- 3326304 TI - [Rational hemostaseologic diagnosis]. PMID- 3326306 TI - [Dresden public health efforts and their fate in the 1st half of the 20th century]. PMID- 3326305 TI - Blood glucose and plasma insulin responses to fat-free milk and low-lactose fat free milk in young type 1 diabetics. AB - The blood glucose and plasma insulin responses to test milk samples were studied in eight insulin-dependent diabetics. After an overnight fast, the subjects (aged 20-45 years) were given a breakfast containing two Weetabix biscuits (20 g carbohydrate) with 500 ml of either regular (S) fat-free milk (25 g lactose) or 500 ml of a new low-lactose (D) fat-free milk (3.75 g lactose and 4.25 g fructose). The regular morning insulin dose was omitted. Mean basal plasma glucose level was slightly higher before S milk (11.4 vs. 10.1 mmol/l). The peak increment in plasma glucose was higher in S milk (9.4 vs. 6.6 mmol/l). The rise was 83% above basal (S) vs. 65% (D). Although the final mean plasma glucose concentration was not significantly higher 3 h after S milk compared with D milk (17.9 vs. 14.3 mmol/l) the incremental area under the plasma glucose curve was much greater (p less than 0.001) with S milk than with D milk (1266 +/- 295 units vs. 909 +/- 242 units). No galactose was detectable in any sample and there was no difference in plasma beta-hydroxybutyrate levels. The results suggest that the low-lactose fat-free milk (D) may be suitable for diabetic diets and weight reducing diets due to the lower contribution of energy. The results suggest that fat-free milk does not exert a fast action on blood glucose concentration and therefore fat-free milk and especially low-lactose fat-free milk may also prove to be suitable for diabetic diets. PMID- 3326307 TI - [Development of public health as a university discipline in Dresden]. PMID- 3326308 TI - [Role of Pseudomonas maltophilia and "Pseudomonas like bacteria group Va" in the etiology of Crohn disease]. AB - In 1976, Parent and Mitchell isolated cell-wall defective bacteria of the species Pseudomonas maltophilia and Pseudomonas like bacteria group Va from resected bowel tissue of 8 consecutively operated patients with Crohn's disease. The control group, which included patients with ulcerative colitis, was negative in this respect. The isolated strains were available for our own investigations. New Zealand white rabbits were inoculated with killed bacteria to produce specific antisera. Frozen sections of affected tissue from 6 consecutively operated Crohn patients were incubated with the various antisera and investigated by indirect immunofluorescence. No positive reactions were demonstrable in repeated tests with different dilutions of antisera. Our results do not support the hypothesis that bacteria of the species Pseudomonas maltophilia and Pseudomonas like bacteria group Va are an etiologic factor in Crohn's disease. PMID- 3326309 TI - [Interdigestive motility and secretion of the gastrointestinal tract]. AB - In the fasting state, the digestive tract is not inactive but displays periodic motor and secretory activity. Each gastrointestinal motility cycle can be divided into specific phases of activity: a period of inactivity (phase I), followed by a longer period of irregular activity (phase II) and by a brief, conclusive period (phase III) of maximal, rhythmic contractions, the migrating motor complex (MMC), which migrates from the gastroduodenal region to the distal small bowel within one motility cycle. A short, inconstant transition segment between phases III and I is termed phase IV. Lower esophageal, gallbladder and sphincter of Oddi motilities are also linked to this functional cycle. In contrast, colonic motility follows independent patterns. Closely correlated to upper gastrointestinal motility are secretory activities: Output rates of gastric, pancreatic and bile secretions increase and decrease periodically, in concert with upper gastrointestinal motor activities. The physiologic role of periodic interdigestive activity is not fully understood. It is probably important for regular mechanical and enzymatic cleansing ot the gastrointestinal lumen and may serve to remove indigestible and/or foreign material, to prevent bacterial overgrowth or pathologic activation of pancreatic enzymes, and to revert duodeno gastric and ceco-ileal refluxes. Control of the interdigestive cycle and mechanisms of motor/secretory coupling have been only partly uncovered; however, recent findings suggest that interactions between vagal and intrinsic cholinergic pathways and gastrointestinal hormones may play pivotal regulatory roles. PMID- 3326310 TI - [Single dose treatment with H2-receptor-antagonists: is bedtime administration too late?]. PMID- 3326312 TI - [Imaging of aortocoronary bypasses with intravenous digital subtraction angiography]. AB - We examined 24 patients with 52 coronary bypass grafts, an average of 18 months after their respective operations. During the course of 1 week, a coronary angiography and a digital subtraction angiography (DSA) incorporating an intravenous injection of contrast medium were performed. Conventional coronary angiograms showed 40 bypasses as being open, ten as being occluded, and two could not be displayed at all. With the aid of digital angiography, 50 out of 52 bypasses could be classified as either open or occluded. In 44 out of 52 bypasses, DSA and coronary angiogram results were identical. Using DSA, three out of ten angiographically occluded bypasses were falsely diagnosed as being open and three out of 40 open bypasses as occluded. Two bypasses could not be interpreted due to poor picture quality. In the diagnosis "open bypass" the degree of both sensitivity and specificity subsequently amounted to 92.5%, and 70% in the diagnosis "occluded bypass". The distal part of the bypasses, as well as the proximal and distal part of the anastomoses, could not be evaluated for the most part. Furthermore, on account of the comparatively inferior quality of the pictures, detection of bypass stenosis is not reliable using digital subtraction angiography. Intravenous digital subtraction angiography may therefore serve as a screening method in the evaluation of coronary bypass grafts. PMID- 3326311 TI - [Reactions to fragrances and textiles]. AB - Allergic reactions to fragrances are caused by perfumes and perfume-containing items of our environment. The most important allergen is cinnamic aldehyde. By means of the mixed perfume test recommended by the International Contact Dermatitis Research Group (ICDRG), however, we are not able to detect more than half of the patients suffering from perfume allergy. Thus we suggest to make use of two new test series comprising most of the relevant fragrance components. Allergic reactions to textiles are mostly due to textile dyes. Special regard must be given to the disperse dyes of the azo group in nylon stockings and tights. The three most important allergens are disperse yellow 3, disperse orange 3, and disperse red 1. According to our experiments, the sensitizing potency of these dyes is comparatively low. In contrast, two recently introduced azo dyes (disperse blue 106 and 124), which are mainly used in blouses and trousers, proved to be strong sensitizers. PMID- 3326313 TI - Technology and laboratory investigation of perfusion and transfusion techniques. PMID- 3326314 TI - Changing concepts in the diagnosis and management of patients with valvular heart disease: a clinician's view. AB - The epidemiology, natural history, diagnostic evaluation and therapy of patients with valvular heart disease have changed during the last 25 years in developed countries. The incidence of rheumatic heart disease has declined, while degenerative forms of valvular heart disease have become more common; arteriosclerotic heart disease commonly complicates valvular disease. A variety of non-invasive techniques demonstrate with considerable accuracy the presence and severity of valvular lesions. Both medical and surgical therapy for valvular heart disease have improved; the prognosis for these patients is far better today than it was 25 years ago. PMID- 3326315 TI - [Competence in the aged]. AB - Cohort-sequential analyses of intelligence, personality variables, health and social data show that prerequisites for aging in competence today are better met in industrialized societies than a few decades ago. It is argued that a competence model of aging should complement the traditional defect and disuse models. Competence is defined by situational demands as well as by a person's resources to meet these. Emphasis on competence allows for specific (not general), variable (not constant), and relatively individual (not universal) descriptions and explanations of development. Chances for intervention with the aged are illustrated. PMID- 3326316 TI - [Maintaining competence by physical activity and sports--circulatory physiologic and sports medicine prerequisites]. AB - With increasing age, there is a change in the mitochondrial pattern of muscle tissue which leads to a loss of compliance of the arterial vessel wall and therefore to a slight change in contraction mode of the heart and also to a decrease of stroke and circulation volume. In the same way, lung function parameters such as vital capacity and forced ventilatory capacity are changes in the elderly. In addition to these, a higher incidence of general disease will change the organism, particularly heart circulation and the pulmonary system. In order to judge physical performance and sporting activity, certain physiological and pathophysiological features of aging have to be taken into consideration in the elderly. Avoiding any risks should be always above to intention of gaining a better physical condition, although this is desirable in principle. PMID- 3326317 TI - [Competent aging with sports]. AB - This contribution deals with the significance of sports for competence in old people. It presents evidence for positive effects of sporting activities on the solution of self-development tasks, like maintaining social participation in old age, pursuing one's own interests, or on keeping active in general, as well as on indices of life-satisfaction like the feeling of well-being, emotional adjustment, or a sense of self-control. In its second part, the paper develops a series of recommendations concerning the motivation of aging persons to sports and the realization of sporting activities for them. PMID- 3326318 TI - [Coping in the aged--results and problems of psychological studies of coping behavior in the elderly]. AB - Recent research in the psychology of aging places increasing emphasis on the coping concept as a means of explaining the psychological consequences of stresses and demands at old age. Nevertheless, only a few empirical studies on the coping behavior of aging people have been made. These studies show the following: (a) coping varies with age, as well as with sex differences, (b) coping strategies differ according to the actual characteristics of daily hassles, critical life events, and persistent life-strains, (c) coping strategies differ also according to the subjective appraisal of these events, (d) there is no evidence for the protective function of coping behavior in general, but only for specific coping strategies. Although there is some speculation about the "growth" and "regression" hypotheses, there are, as yet, no studies on this question. The author concludes by considering some theoretical and methodical problems of coping research in gerontology. PMID- 3326319 TI - [Subjective well-being in the aged. Status of research and theoretical development]. AB - A review of research on well-being in later life is given, to achieve a theoretical elaboration of the field. The independence of positive from negative affect is shown first of all. This confirms well-being as autonomous psychological construct. A review of empirical research on the variations of well being in later life indicates almost no coherent trends. This leads to severe problems in well-being research: uncomparable research instruments, contamination of indicators and correlates, ideological biases, ahistoricity, and lack of theoretical foundations. A review of factor analyses of well-being and theoretical considerations support a four-component approach: joy, negative affect, life satisfaction, and happiness. Together with familiar constructs, they are arranged in to a conceptual field of well-being. Finally fragments of theory are collected to develop a model of causal factors of well-being. PMID- 3326320 TI - [Neopterin as a parameter for the early detection of acute graft rejection following heart transplantation]. PMID- 3326321 TI - [Modification of isolated malate dehydrogenase and aspartate aminotransferase by E. coli endotoxin]. PMID- 3326322 TI - [The history of Salzburg and its university and the development of pathology in this country]. PMID- 3326323 TI - [The biology of the pancreas]. PMID- 3326325 TI - [Pathology of the pancreas in chronic type 1 diabetes mellitus: B-cell content, exocrine atrophy and angiopathy]. PMID- 3326324 TI - [Comparative pancreatic pathology]. PMID- 3326326 TI - [Immunohistochemical and electron microscopy studies of the donor pancreas]. PMID- 3326327 TI - [Pathophysiology of the exocrine pancreas]. PMID- 3326328 TI - [Acute pancreatitis. Morphology and pathogenesis]. PMID- 3326329 TI - [Pancreatic cancer]. PMID- 3326330 TI - [The "new morphology" in pancreatic diagnosis--ultrasound, computerized tomography, nuclear magnetic resonance imaging]. PMID- 3326332 TI - [Immunologic therapeutic approaches in malignant diseases, especially in pancreatic tumors]. PMID- 3326333 TI - [The endocrine pancreas in chronic pancreatitis]. PMID- 3326331 TI - [Compartmentation and protein transport in the acinar cell of the pancreas as a pathophysiologic concept]. PMID- 3326334 TI - [Immunohistochemical demonstration of the diffuse neuroendocrine system in various pancreatic lesions]. PMID- 3326335 TI - [Value of various neuroendocrine cell markers in the immunohistochemical diagnosis of neuroendocrine tumors of the gastroenteropancreatic system]. PMID- 3326336 TI - [Chromogranin A and B and secretogranin II in the endocrine pancreas]. PMID- 3326337 TI - [Inflammatory pseudotumor of the pancreas with persistent hyper-insulinemia and hypoglycemia following long-term pancreatic transplantation]. PMID- 3326338 TI - [Salzburg and Paracelsus]. PMID- 3326339 TI - [The exocrine and endocrine pancreas and their reciprocal relations]. PMID- 3326340 TI - [The papilla of Vater and the pancreas]. PMID- 3326341 TI - [The bile ducts and pancreas]. PMID- 3326342 TI - [Werner Schopper (4 September 1899-20 December 1984)]. PMID- 3326343 TI - [Hermann Hager (12 June 1923-22 July 1986)]. PMID- 3326345 TI - [German Society for Pathology: list of members]. PMID- 3326344 TI - [Jaroslav Svejda (31 July 1915-26 September 1986)]. PMID- 3326346 TI - [Pancreatic diseases and other organs]. PMID- 3326347 TI - [Systemic diseases and the pancreas]. PMID- 3326348 TI - [Pancreas transplantation]. PMID- 3326349 TI - [Morphometric studies of the development of the human pancreas from the 12th to the 30th week of pregnancy in relation to the mesenchyme, parenchyma, islands and free cell groups]. PMID- 3326350 TI - [Etiology and pathogenesis of bullous pemphigoid]. PMID- 3326351 TI - [2 cases of cicatricial pemphigoid with skin lesions]. PMID- 3326352 TI - [Atrophic pustulosis of the legs]. PMID- 3326353 TI - [Thermoregulation in rodents of different ecological niches in experimental adaptation to cold]. PMID- 3326355 TI - Antenatal torsion of the uterine adnexa in a neonate. AB - An antenatal detection of unilateral torsion of uterine adnexa was made by means of ultrasonography on the 32nd gestational week. This presented as an asymptomatic large "pseudo-cystic" mass, and was resected electively at the age of two weeks. A "fluid-fluid" level on ultrasonography is highly suggestive of this rare entity. This is the fourth case in the English literature to have been detected antenatally, and among the first dozen to be reported in the neonatal period. PMID- 3326354 TI - [Standstill in the epizootology of plague--the reasons for it and the means of surmounting it]. PMID- 3326356 TI - [Generalized tendomyopathy: psychological profile of a patient group in the course of integrated treatment]. AB - 27 patients suffering from fibrositis were studied using a series of psychological tests in the course of an integrated group treatment program. In addition, their behaviour in the treatment program was observed and information about their behaviour in interpersonal conflicts was gathered. The results confirmed earlier observations that these patients show similar patterns in a projective test (Rosenzweig Picture Frustration Test) as patients with other rheumatic or other psychosomatic affections. The observations in the group sessions gave further support to these findings. However, in their self evaluation with a personality inventory (Freiburger Personlichkeits-Inventar), these people described themselves as more disturbed than the other kinds of patients mentioned. But this disturbance seems to be rather the consequence than the cause of this chronic illness of unclear origin. These signs of emotional disturbance were more distinct in those patients who had been suffering for longer from their illness and showed a poorer response to our treatment program. PMID- 3326357 TI - [CRST syndrome and primary biliary cirrhosis]. AB - The case of a female patient with the history of amanita poisoning, CRST syndrome and primary biliary cirrhosis (PBC) is reported. Immunological features (IgM rheumatoid factor, antinuclear-, anticentromere- and antimitochondrial antibodies) and HLA-antigens are studied. Immunological abnormalities occurring in CRST and PBC suggest a common autoimmune base, which also makes concomitance of these two disease states more than coincidental. PMID- 3326358 TI - [Arthritis in colitis ulcerosa and Crohn disease]. PMID- 3326359 TI - [Surface structures of potentially arthritogenic microorganisms]. PMID- 3326360 TI - [Inflammatory diseases of the intestine]. PMID- 3326361 TI - [Reactive arthritis in enteral infections]. AB - Certain gastrointestinal tract infections can trigger reactive arthritis. The best known triggering agents are yersinia, salmonella, shigella, campylobacter jejuni, and possibly clostridium difficile. The clinical findings show a subacute onset of mono- or oligoarthritis, less often of asymmetric polyarthritis with predominance of the lower limbs. The clinical picture is somewhat modified by the genetic constitution (HLA type) of the patient. HLA-B27-positive patients appear to have more severe symptoms, extraarticular features and incomplete or complete Reiter's syndrome than HLA-B27-negative patients. Diagnosis of postenteritic reactive arthritis is based on bacteriological stool analysis and/or examination of serumantibodies to the corresponding agents. Reactive arthritis is usually self-limiting and therefore treatment of the disease has to be mainly symptomatic. Only more severe chronic or destroying arthritis is thought to be treated locally (i.e. by synoviorthesis) or by immunoregulatory drugs. PMID- 3326362 TI - [Immune phenomena in liver diseases]. PMID- 3326363 TI - [Arthritis in liver and pancreatic diseases]. PMID- 3326364 TI - [Involvement of the gastrointestinal tract in connective tissue diseases]. PMID- 3326365 TI - [Side effects of antirheumatic therapy on the gastrointestinal tract]. PMID- 3326367 TI - [Our surgical heritage. The 1st surgeon of Berlin University--on the 200th birthday of Carl Ferdinand von Graefe]. PMID- 3326366 TI - [Our urologic heritage: Leopold Casper (1859-1959)]. AB - It is reminded of the outstanding Berlin urologist Leopold Casper (1859-1959), whose work reflects half a century of the history of Berlin urology. As founder of the ureteral catheterisation and the functional renal diagnostics he helped the urology, for the recognition of which as an undependent subject he fought a life-long struggle, to further reputation. PMID- 3326368 TI - Studies on clonal assignment of urinary Escherichia coli O1:K1 strains. AB - Fifty-nine Escherichia coli strains belonging to two clonal groupings were investigated for major outer membrane proteins, colicin production, and partly for plasmid DNA content. The membrane protein patterns of the 01:K1:H7(H-):F11 and O1:K1:H-:F9 strains obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were distinctly different from each other and, therefore, are useful for clonal assignment. All of the F11 isolates had one plasmid of about 85 Md in common which is suggested to be characteristic for the clone. Their content of smaller plasmid DNA was heterogeneous and showed geographical differences. The F9 strains showed a plasmid pattern different from the F11 strains. A plasmid of 2.6 Md was found in all of these isolates. Colicin production was found to be useful for clonal assignment only in two thirds of the F9 and not in the F11 strains. Some strains with identical properties seem to be of epidemic importance. PMID- 3326369 TI - Evaluation of a small "conventional" identification system for fermentative gramnegative rods using a computerized data base. AB - A small "conventional" identification system consisting of six tubed media totalling eleven reactions was used to identify 467 strains of Enterobacteriaceae, 15 strains of Aeromonas sp., and 3 strains of Plesiomonas shigelloides. The system identified 371 strains (76.5%) correctly to maximum identification (species or genus) level and an additional 13 strains (2.7%) to genus level where species level identification would have been possible. Ninety strains (18.6%) were not identified. Only 11 strains (2.3%) were misidentified. The system is inexpensive compared with commercial systems and can be used for primary identification of fermentative gramnegative bacteria in a clinical microbiology laboratory. It comes with a computerized data base in the form of an identification manual. PMID- 3326370 TI - Phenotypic differentiation of members of the family Vibrionaceae using miniaturized biochemical tests. AB - Enzymatic hydrolysis of 27 different chromogenic substrates and the assimilation of 44 carbon sources by 144 strains of Vibrio species of clinical importance, Aeromonas hydrophila and Plesiomonas shigelloides were studied by standardized micromethods. Some classical biochemical tests were also performed using the test kit TTE-AS (Flow Laboratories GmbH, Meckenheim, FRG). Reading of results was done automatically by a photometer and test data were recorded and stored by a microcomputer. All species investigated could be differentiated using a set of 16 miniaturized biochemical tests which are: Indole production, esculin hydrolysis, lysine decarboxylase, ornithine decarboxylase, arginine dihydrolase, fermentation of sucrose, enzymatic hydrolysis of o-nitrophenyl-beta-D-galactopyranoside, gamma L-glutamic acid-p-nitroanilide and the assimilation of L-arabinose, D-cellobiose, D-mannose, sucrose, D-mannitol, i-inositol, acetate and DL-lactate. Comparing the TTE-AS tests to conventional test results, 94.4% overall agreement was found. 87.6% of the miniaturized assimilation tests agreed to literature data. The described tests are easy to perform and seem to be suitable for routine laboratory use. PMID- 3326371 TI - Simplified identification of bacteria belonging to the genus Salmonella. AB - A new, simplified procedure for identification of bacteria belonging to the genus Salmonella is reported. By this procedure which is a new combination of well know tests, Salmonella spp. are easily and reproducibly differentiated from non Salmonella spp. after 6 h of incubation at 37 degrees C. PMID- 3326372 TI - Fatal Legionella pneumonia: retrospective examination of lung tissue using direct and indirect fluorescent-antibody methods. AB - Lung tissue sections of patients who died of pneumonia within one year were screened retrospectively for Legionnaires' disease bacteria using simultaneously a direct fluorescent antibody test (DFA) and an indirect fluorescent antibody system (IFA). The IFA has shown to provide a rapid screen for the increasing number of known Legionella species and serogroups recently. In 10/168 (6%) of our cases legionellae were the pneumonia causing agents detected with both methods. Although we should have been able to detect 25 serological variants of Legionella species and serogroups with the IFA, we found Legionella pneumophila serogroup 1 only. The IFA test has proven to be a reliable means for the screening of lung tissue sections. PMID- 3326373 TI - [Comparison of the results of the measurement of O2 consumption with a conventional bacteriologic method for urine obtained by bladder puncture]. AB - A method is described which utilizes the O2 consumption of aerobes and facultative aerobes from urinary tract infections for their detection. Urines obtained by puncture and the corresponding midstream urines were examined for verification. Irrespective of secondary contamination and the presence of non causative organisms, the O2 consumption method permits the detection of a bacterial urinary tract infection within 1 h. When this method was used, a comparison between midstream urine and urine obtained by puncture showed a complete coincidence. The O2 method has shown a sensitivity of 96.9% at a specificity of almost 100% for bacterial concentrations of more than 10(5)/ml in the urine obtained by puncture. PMID- 3326374 TI - Investigations on the binding of erythrogenic toxin A of Streptococcus pyogenes on human peripheral blood lymphocytes. I. Light and electron microscopical demonstration of cell surface receptors using colloidal gold-labelled toxin. AB - Receptors for erythrogenic toxin A (ETA) of Streptococcus pyogenes (strain NY-5) were demonstrated on human peripheral blood lymphocytes by binding of ETA-gold conjugates to the cell surface. The specificity of the binding was proved in control experiments. The dark-red granules observed by light microscopy on unfixed cells were revealed by transmission electron microscopy to be patches of gold particles. By light microscopy on samples from 48 blood donors a mean value of 34 +/- 13% of ETA-receptor bearing lymphocytes was ascertained. The predominant part of the cells exhibited only a weak or moderate labelling. Transmission electron microscopy of prefixed cells revealed an attachment of single gold particles distributed over the whole cell surface. Counts of gold particles on serial sections yielded depending on prefixation values of 50-600 receptors/cell (1% glutaraldehyde) and 1000-7000 receptors/cell (0.26% glutaraldehyde), respectively. ETA cloned in Streptococcus sanguis as well as the toxoid of ETA exhibited a comparable binding as ETA (NY-5). PMID- 3326375 TI - Hydrophobicity of Candida albicans related to their adherence to mucosal epithelial cells. AB - A total of 150 Candida albicans strains were examined, using a salt aggregation test (SAT) and an improved salt aggregation test (ISAT). The fungal strains were isolated from patients or taken from a collection. Out of 150 strains, 20.7% were autoaggregating in the ISAT. In the SAT, 12% of the strains were autoaggregating in saline and 14% in phosphate buffer. The remaining strains did not clump. Pretreatment of the autoaggregating strains with detergents (Tween 80 and ethylene glycol) prevented aggregation in some of them. The adherence capacity to buccal epithelial cells of the fungal strains autoaggregating in the SAT and ISAT, was compared to that of the nonaggregating ones. The autoaggregating strains revealed significantly higher adherence values (p less than 0.002). The adherence ability to buccal epithelial cells of the autoaggregating strains before and after their pretreatment with detergents was compared. The adherence values after pretreatment were significantly lower (p less than 0.001). PMID- 3326376 TI - The role of cell population kinetics in the efficacy of penicillin--an experimental analysis and stochastic modeling of the tumour tetanus and wound tetanus of the mouse. AB - When investigating tetanus lethality summation curves of mice under comparable quantitative conditions following a temporarily limited administration of penicillin, the curves obtained can be calculated by the kinetics of tumour cells or wound fibroblasts. In particular, it has been shown that the optimal efficacy of penicillin, after short-time usage as compared with a long-time administration schedule, is determined by the generation time of the tetanus rods as a function of the mitotic cycle of the "pace-making" tumour cells or wound fibroblasts. Further variables of the mathematical model imply the pharmacokinetics of penicillin and the recovery process of the "hit" tetanus rods. From these results some basic experimental and clinical tetanus issues can be elucidated; thus, the mitosis theory of tetanus is being verified for the stage of incubation and of clinical manifestation, while the classical necrosis theory of the pathogenesis of tetanus infection should be valid only for the final stage. PMID- 3326377 TI - [State control of animal epidemics and their occurrence in the European Community]. PMID- 3326378 TI - Testing phagocytic capacity of porcine blood polymorphonuclear leucocytes using laser flow cytometry. PMID- 3326379 TI - [The development of evolutionary physiology and biochemistry in the USSR]. PMID- 3326380 TI - Prevalence of residual B-cell function related to age at onset and genetic profile in newly diagnosed type I diabetics. AB - Patients with type I (insulin-dependent) diabetes mellitus maintain B-cell function for a varying period of time after onset. This is commonly held to account for post-initial remission. To estimate residual B-cell function we measured plasma and 24-h urinary C-peptide in 68 type I diabetic patients (age range 4-35 years, within 10-180 days of the onset of symptoms, typed for HLA-A, B, -C and DR loci. A positive correlation (r = 0.26; p less than 0.05) was found between urinary C-peptide levels and the age of the patient. The analysis of variance of urinary C-peptide values on the basis of the presence or absence of DR3 and DR4 antigens revealed that the DR3-positive patients had reduced excretion (15.2 +/- 9.2 SD micrograms/24h) with respect to the others (22.7 +/- 15.5 SD micrograms/24h) (F = 6.35; p less than 0.05). No interaction effect was found in DR3/4 positive patients. Hence, late onset patients appear to have higher residual C-peptide secretion. In the light of these findings, the assessment of B-cell function and genetic profile may be useful in predicting which patients are likely to have remission periods and identifying the metabolic consequences of even minimal endogenous insulin secretion. PMID- 3326382 TI - [Anorectal melanomas. Presentation of a case and literature review]. PMID- 3326383 TI - Hepatobiliary complications in chronic inflammatory bowel disease. PMID- 3326381 TI - Hyperglycemic effects of hydrochlorothiazide and propranolol. A biochemical and ultrastructural study. AB - The authors studied the glycemic disturbances provoked by two antihypertensive drugs, propranolol and hydrochlorothiazide, administered alone or in combination to normal and diabetic rats, using biochemical and ultrastructural parameters. It was found that hydrochlorothiazide raised fasting glucose concentration significantly; propranolol alone caused an insignificant rise of glucose, but significantly aggravated the effect of hydrochlorothiazide with an additive interaction. The ultrastructural findings, as well as the urinary C-peptide excretion, confirmed that the glycemic effects should not be thought to be due to a direct action of the drugs used on the endocrine pancreas. PMID- 3326384 TI - [Orthotopic liver transplantation. Belgian experience up to 1986]. PMID- 3326385 TI - [Prognosis of hepatic transplantation as a function of biological, immunological and functional preoperative findings]. PMID- 3326386 TI - [Medical expert and consultation systems: review and examples for their use]. AB - After a general introduction into the area of medical expert and consultation systems, a survey about different types of medical expert systems is given. The different objectives and modes of application of medical expert systems are presented and explained in detail. In the second part of this paper, the applicability of computer systems for fully automated interpretation of hepatitis serology findings in the clinical laboratory and for aiding differential diagnosis in internal medicine is described. With the examples given, it is demonstrated that expert systems for clinical decision aid can be of great benefit for the physician in the hospital or the doctor's office. PMID- 3326387 TI - [Objective tissue differentiation in sonography using local texture analysis]. AB - An approach to differentiating tissues by means of local texture analysis is described and its diagnostic power is evaluated using various diseases of the liver, kidney and the prostate. PMID- 3326388 TI - Antibiotic resistance and plasmid profiles of Escherichia coli and Klebsiella isolated from in-patients receiving prolonged antibiotic therapy. AB - Distribution by serogroup, phage type, colicin production, colicin type, sensitivity to antibiotics and plasmid characteristics of 74 Escherichia coli and 11 Klebsiella strains isolated from hospitalized patients receiving prolonged antibiotic therapy indicated that the infections were not associated with the hospital environment. Resistance was tested to 26 antibiotics, some of them being not generally used in therapy; 30 strains were resistant to 4 to 17 antibiotics. There was a significant difference in the antibiotic resistance of strains derived from patients with urinary-tract infections (UTI) and with leukaemia (LP). As compared to the UTI group, among E. coli strains in the LP group the frequency of multiple resistance was significantly higher, the MIC values were higher and R-plasmids were more frequent. Out of 30 multiple resistant E. coli strains 27 were R-plasmid carriers. Three different kinds of plasmid profile were shown in more than one strain (2 out of 10 UTI strains and 3 and 2 out of 10 LP strains). The rest of the isolates differed in plasmid profile from these and from one another; the presence of "epidemic plasmid" was not demonstrated. Plasmid epidemiological examinations may forecast the efficacy of an antibiotic or of a group of antibiotics. PMID- 3326390 TI - Protective value of the plasmid-coded outer membrane protein of enteroinvasive Escherichia coli. AB - O-antigenically not related enteroinvasive Escherichia coli strains and rabbit sera prepared with them were used to study the role of plasmid-coded outer membrane proteins in protective immunity. Active immunization experiments were performed using a mouse model based on a long-lasting symptomless carriership after elimination of the bowel flora by streptomycin. Preliminary histological studies showed adhesion, penetration, intraepithelial multiplication, and epithelial desquamation after infection. In active immunization experiments only massive oral doses evoked protective immunity. Seroconversion against the plasmid coded antigens was not observed in mice. Passive immunization was carried out in chick embryos with unabsorbed sera. A high level of protectivity was reached by serogroup-specific sera and a very low but significant protection was yielded by antibodies against the plasmid-coded protein antigens. PMID- 3326389 TI - IgG response of dysenteric patients to antigens coded by the virulence plasmid of enteroinvasive pathogens. AB - IgG antibody response to antigens coded by the virulence plasmid of enteroinvasive pathogens was studied in dysenteric patients by ELISA. A plasmidless Escherichia coli K-12 strain and its transconjugant harbouring the 140 megadalton plasmid of a virulent E. coli 0124 strain were used as antigens. Sera of 12 dysenteric patients taken on the first, third an twelfth week after Shigella sonnei infection were examined. For comparison sera of 23 nondysenteric persons were also applied. Titres of the first week samples did not differ significantly from those of the controls. Patients' sera taken on the third week showed a fivefold rise in titres as compared to the first week ones. Antibody activity remained on a comparable high level till the twelfth week. The data prove that there is a considerable IgG response to plasmid coded antigens common in shigellae and enteroinvasive E. coli. PMID- 3326391 TI - Paper-disc method for Campylobacter hippurate-hydrolysis test. A note. AB - Paper discs were impregnated with sodium hippurate dissolved in 1/15 phosphate buffer pH 7.2. The discs, each containing 2 mg substrate, were stored in dry state at room temperature. After adding a disc to bacteria suspended in distilled water, and incubated at 37 degrees C for 2 h, one drop of Skirrow and Benjamin's ninhydrin reagent was added and the reaction was read after re-incubation at 37 degrees C for 10 min. 169 campylobacter strains were tested. The results for a total of 169 strains were identical with those obtained with the modified rapid method of Skirrow and Benjamin. Of 92 campylobacter strains isolated from human faecal samples 59.8%, of 36 strains isolated from slaughtered poultry 41.7% proved to be Campylobacter jejuni. PMID- 3326392 TI - Background factors and management of ectopic pregnancy in Sweden. Changes over a decade. AB - Hospital records of all women operated on for ectopic pregnancy (EP) in four Swedish towns during 1970-72 and 1980-82 were elaborated. The gynecological and obstetrical background was noted and the clinical picture and management was recorded and analysed. The incidence of EP more than doubled between the two periods. There was no major change in classical background factors between the periods, but the proportion of IUCD users rose from 4 to 16 percent. The use of hCG assays, curettage and ultrasound in establishing the diagnosis increased markedly and the proportion of women with ruptured tubes and heavy intra abdominal bleeding decreased. Moreover there was a clear tendency towards a more conservative surgical approach in the latter period. PMID- 3326393 TI - Induction of labor and cervical ripening with oral PGE2 in risk pregnancies. A placebo-controlled study. AB - A double-blind, placebo-controlled study was undertaken to evaluate the priming effect on the cervix and also the effect on the subsequent induction of labor. 0.5 mg oral PGE2 or placebo was given hourly for two 12-h periods. A total of 191 women with risk pregnancies and Bishop score less than or equal to 5 were studied. The induction of labor was carried out with oxytocin or oral PGE2 in a randomized manner. Labor was induced in 39% of the women during the PGE2 priming. The best result, 71% vaginal deliveries, was achieved with the combination of PGE2 priming and induction of labor with oxytocin. PMID- 3326394 TI - Sonography of umbilical cord hematoma following genetic amniocentesis. AB - A case of umbilical cord hematoma, following genetic amniocentesis, is reported. Spontaneous resorption of the hematoma was observed at sonography. A normal infant was born vaginally at term. PMID- 3326395 TI - Characteristics of histiocytic lesions in the reticuloendothelial system of NZB mice. AB - The so-called Potter's lesion, previously described as preneoplastic in the lymph nodes of C58 mice, develops frequently in autoimmune NZB mice. These lesions were characterized in the present study by bands or sheets of pale-staining histiocytic cells in the cortex and medulla of the lymph node, and multiple small nodules of the same cells were found in the red pulp of the spleen and the liver. Electron microscopically, the cells had pleomorphic cytoplasm with long processes, electron-dense bodies, abundant mitochondria, and a characteristic labyrinth structure with many C-type viruses. Mac-1 antigen, IgG-Fc receptor, ferritin, and ACPase activity were identified on these cells. Intraperitoneally injected iron colloids were found in the lesions of the spleen and liver but not in those of the lymph nodes. The lymph node lesions appeared when the mice were about 3 months of age and enlarged until the mice were around 10 months old, after which they gradually receded and were replaced by small vessels and fibroblastic cells. These data indicate that the lesions represent reactive hyperplasia of the macrophage system and may have no direct association with the development of malignant lymphoma in NZB mice. PMID- 3326396 TI - Studies on glomerular immune solubilization by complement in patients with IgA nephropathy. AB - A study of the solubilization of glomerular immune deposits by serum or complement in patients with IgA nephropathy is described. Renal biopsy specimens were obtained from 15 patients with IgA nephropathy. These specimens were incubated with fresh and heated sera from healthy adults or with lyophilized complement components, i.e., C3 and C4, at 37 degrees C for one hour in plastic tubes. The sections were then stained with fluorescein isothiocyanate (FITC) labelled anti-human IgA antisera and examined by fluorescence microscopy. Normal sera showed a marked capacity to solubilize the glomerular immune deposits characteristic of IgA nephropathy. The solubilization capacity was reduced after inactivation and absorption of sera with anti-human C3 antiserum. Lyophilized C3 or C4 did not show any ability to solubilize such deposits. It was concluded that the solubilization of glomerular immune deposits may require whole active (fresh) components of complement related to the alternative pathway. PMID- 3326397 TI - Familial hemophagocytic reticulosis. Clinicopathologic findings and cytochemical, immunohistochemical and electron microscopic studies. AB - Clinicopathologic findings of a case of familial hemophagocytic reticulosis (FHR), for which splenectomy, and biopsy of the liver and mesenteric lymph nodes were performed, is reported. Histologically, the proliferated cells consisted of not only histiocytes showing severe erythrophagocytosis, but also lymphoid cells of various sizes. The lymphoid cells had atypical features including mitotic figures and convoluted nuclei, and were suspected to be T cells as a result of immunohistochemical studies. We therefore consider that FHR is a special type of lymphoproliferative disease accompanied by severe proliferation of erythrophagocytic histiocytes rather than being a true histiocytic disease. Cytochemical and electron microscopic findings of the involved spleen are also presented. PMID- 3326398 TI - In vitro activity of ceftazidime, cefotaxime and gentamicin against 11,521 clinical isolates of bacteria. AB - The in vitro activity of ceftazidime has been compared with those of another third-generation cephalosporin, cefotaxime, and the aminocyclitol aminoglycoside, gentamicin. A total of 11,521 clinical isolates of aerobic bacteria were employed, and an agar diffusion method was used for sensitivity testing. The MIC values were calculated from regression lines. The mean inhibition zones for ceftazidime against Gram-positive organisms were significantly less than those against Gram-negative isolates (23 mm vs. 33 mm, p less than 0.0001). Cefotaxime inhibited 74.0%, gentamicin 66.3% and ceftazidime 20.4% of the Gram-positive isolates at a concentration of less than or equal to 2 mg/ml. Ceftazidime and cefotaxime were equally active against fermentative Gram-negative rods, inhibiting 92.7% of each of these isolates at 2 mg/l. Against Ps. aeruginosa, ceftazidime (MIC90 2.2 mg/l) was found to be almost as active as gentamicin (MIC90 1.2 mg/l), and far more active than cefotaxime (MIC90 434 mg/l). Gentamicin was the most active agent against Acinetobacter sp. (MIC90 6.0 mg/l), followed by ceftazidime (MIC90 18 mg/l) and cefotaxime (MIC90 83 mg/l). PMID- 3326400 TI - Correlation of the fibrinogen level with blood pressure and plasma renin activity in rats with early Goldblatt hypertension. AB - Goldblatt hypertension was induced in rats by constricting the renal artery on one side. In one group of animals the contralateral kidney remained untouched (two-kidney hypertension), while in the other it was removed (one-kidney hypertension). In the two-kidney hypertension group, renin activity was higher than in the control animals, the fibrinogen was normal both in arterial and venous blood while in one-kidney hypertension the PRA was normal, but the fibrinogen was increased. A close significant correlation could be demonstrated between blood pressure and fibrinogen. PMID- 3326399 TI - Ascending urinary tract infections in rats induced by Staphylococcus saprophyticus and Proteus mirabilis. AB - Ascending pyelonephritis was induced by Staphylococcus saprophyticus and Proteus mirabilis both by inoculating the organisms separately and in combination into rat bladders. Bacterial cultures of tissue homogenates showed that pyelonephritis by both bacteria occurred significantly more often in rats where the two organisms were instilled concomitantly, suggesting a synergistic virulence between the two species. The antibody response to the different organisms was the same either the bacteria were instilled separately or in combination. PMID- 3326401 TI - Hormonal regulation of sodium-fluid balance and some hemodynamic parameters in the rat. II. The effect of sodium depletion and sodium loading on rats with inherited diabetes insipidus (Brattleboro strain). AB - The effect of furanthril after an acute (24 hours) and chronic administration (7 days), and the effect of 7-days sodium loading was followed on control Long Evans (LE) and Brattleboro rats with inherited hypothalamic diabetes insipidus (DI). In addition to the routine sodium-fluid balance study, plasma renin activity and prostaglandins excretion were examined. In control LE rats was found a typical diuretic- and natriuretic effect of furanthril only after an acute (14 hours) administration of the drug. This effect was attributed to the stimulation of renal PGE2 synthesis. In sodium-depleted state (7 days after administration of furanthril) the diuretic- and natriuretic effect was missing due to the extensive sodium deficit. In DI rats was found a paradoxical antidiuretic effect of furanthril after either an acute or chronic treatment, which was attributed to the per se stimulated renin-angiotensin system and suppressed PG-synthesis typical for these rats. The conclusion of this studies was that an availability of ADH is necessary for PG-response to sodium depletion. After sodium loading, an exaggerated natriuresis, decreased PRA, and depressed PG-synthesis was found in DI rats. The feedback mechanism between renin axis and prostaglandin system in the absence of ADH was discussed. PMID- 3326402 TI - [Effect of a newly synthesized immunosuppressor on the course of experimental pyelonephritis in mice]. PMID- 3326403 TI - Neural mechanisms of somatic sensory regulation of catecholamine secretion from the adrenal gland. AB - The reflex regulation of catecholamine secretion of the adrenal gland by various somatic afferent stimuli via sympathetic nerves in the efferent limb of the reflex has been of physiological interest since W.B. Cannon studied the subject. The reflex regulation is characteristically interfered with by emotional involvement which made it difficult to analyze the neural mechanisms in conscious subjects and delayed these studies. However, for the last several years, electrophysiological and endocrinological approaches have advanced with the aid of anesthesia. Recent studies on anesthetized animals have proven that the adrenal sympatho-medullary functions are influenced by various somatic afferent stimuli, either natural or electrical stimulation, and that the somatically induced adrenal sympathetic reflex responses result in changes in catecholamine secretions from the adrenal gland. Somato-adrenal sympathetic reflexes contain both spinal and supraspinal reflex components, the spinal component having a segmental reflex organization, whereas the supraspinal component is generalized and non-segmental. The reflexes are excitatory or inhibitory, depending on the stimuli and species of animals, e.g., excitatory by pinching and inhibitory by brushing in rats. The excitatory responses are mainly mediated by somatic unmyelinated C afferent fiber activation, whereas the inhibitory responses are carried by somatic myelinated A afferent activation. The recent finding that sympatho-adrenal medullary function increases at rest in normal rats during aging, and in SHR-SP even during their youth was reviewed. Although no neural mechanism governing the increase in adrenal sympathetic nerve activity for these cases has been determined, the reflex regulation of such activity by somatic afferent and arterial baroreceptor afferent stimulation is well maintained in aged normal rats. These facts suggest the possibility that the sympatho-adrenal medullary functions can somatically be regulated in the aged. The recent study demonstrating that i.c.v. administered CRF increases in sympatho-adrenal medullary functions was reviewed, because central CRF seems to play an important role in controlling the somatically induced sympatho-adrenal medullary reflex. Finally, all these findings from anesthetized animals seem useful in understanding the neural mechanism of the somato-adrenal sympathetic reflex in conscious subjects. PMID- 3326404 TI - Developments in protein microsequencing. AB - The author has described here several methods which have been developed in his laboratory. These methods are explained in the following order: [I] gel electrophoresis; 1) extraction from the conventional polyacrylamide gel, 2) a new polyacrylamide gel electrophoresis system for small peptides. [II] Amino acid composition (rapid and micro methods for hydrolysis of proteins); 1) hydrolysis with a mixture of trifluoroacetic acid and hydrochloric acid, 2) vapour hydrolysis, 3) tryptophan micro-analysis. [III] Amino-terminal sequencing; 1) a sensitive detection method of Edman degradation, 2) N-terminal specific labeling method. [IV] Carboxy-terminal sequencing by carboxypeptidase digestion; 1) field desorption mass spectrometry, 2) the use of detergents or alcohols. [V] Monitoring of amino groups at the DNA binding site of protein. As mentioned in the beginning, techniques in the protein field tend to be behind comparable techniques in the DNA field. In addition, the fact that the most important biological molecules presently studied are made in such small amounts in the cell has demanded the development of techniques using precisely and quickly only micro amounts of protein. Such developments of protein chemistry techniques for purification, composition, sequencing, and chemical modification are very much needed in the cell biology field and close collaboration is required between protein chemistry, biophysics, and modern biology in order to develop the above methodology. PMID- 3326405 TI - Some stereological recommendations for analysis of spongious bone. PMID- 3326406 TI - Evaluation of some osteopathies according to histometric parameters. PMID- 3326407 TI - Histopathology and ultrastructure of tumours and tumour-like lesions of bone. AB - The monograph summarizes the most important data and experience based on the clinicopathological analysis, histological and histoenzymatic examinations of more than 1000 primary tumours and 400 tumour-like lesions of bones. The diagnosis of them has been based on the WHO classification of bone tumours which appeared to be the best in meeting the needs of diagnostic practice. However, in our collection of cases also occurred such cases which did not fit into the WHO diagnostic scheme. They included lesions the separate existence of which could be proved only recently or has remained the matter of discussion, such as periosteal osteosarcoma, clear-cell and dedifferentiated chondrosarcoma, malignant fibrous histiocytoma, the so-called parachordoma, resorptive giant-cell granuloma, reactive periostitis of tubular bones of hands and feet, and the tibial lesion reminiscent of cementifying fibroma. In the majority of types of the tumours and tumour-like lesions of bones electron microscopical examination was carried out (203 cases), the results of which are presented here in a considerable extent. On the one hand, electron microscopy facilitated the diagnosis in some cases, and, on the other hand, it proved as extremely important in solving the problems of histogenesis of some of the lesions. PMID- 3326408 TI - Life stress and psychopathology: progress on research begun with Barbara Snell Dohrenwend. AB - This is a progress report on some of the research that was planned and begun with Barbara Dohrenwend before she died in 1982. The main focus is on two of the studies. One was conducted in New York City; the other is still underway in Israel. The New York study is a retrospective case/control study of social and psychological factors that may put people at risk for developing schizophrenic episodes and episodes of major depression. The Israel research consists of epidemiological, case/control, and family studies of these two disorders together with other types of psychopathology that are inversely related to social class. Preliminary findings from both studies are reported, and their implications for primary prevention are discussed. PMID- 3326409 TI - Buffer effects and threshold effects: an alternative interpretation of nonlinearities in the relationship between social support, stress, and depression. AB - The common interpretation of statistical interactions of global measures of social support and stress in their effects on depression (the "buffer effect" of social support) as reflecting interactive processes within individuals was examined. It was argued that its adequacy depends on incorrect assumptions about the distribution of depressive symptoms within individuals over time and/or different levels of psychosocial adversity. With hypothetical data sets generated under the assumption of a threshold effect in the development of depression and of additive, rather than interactive, effects of social support and stress, it was demonstrated that spurious "buffer effects" of social support can appear in analyses of cross-sectional data. Methodological and substantive implications are discussed, and strategies for study design and data analysis are proposed that allow to assess whether empirical deviations from linearity are more adequately interpreted as a buffer or as a threshold effect. PMID- 3326410 TI - Use of lactate as a base in hemodialysis. AB - The purpose of our study was to investigate the feasibility of using lactate as a complete or partial substitute for acetate in hemodialysis solutions. Six patients, each serving as his own control, were dialyzed once against a dialysis solution containing 40 mM acetate, once against a dialysis solution containing 40 mM DL-lactate and once against a dialysis solution containing 20 mM each of acetate and DL-lactate. Six additional patients underwent hemodialysis using acetate + lactate for a 3-week period, and the blood acid-base values during this period were compared to those obtained during periods when acetate was used. All dialysis treatments were well tolerated without hypotension or other clinical manifestations. When acetate + lactate was used, only a slight delay in the correction of acidosis during dialysis occurred and the net change in the plasma bicarbonate value appeared to be comparable to that measured with acetate. On the other hand, when lactate was used, the increase in the plasma bicarbonate level during and immediately after dialysis was reduced. With acetate + lactate, intradialytic blood D-lactate levels remained between 1 and 2 mM and returned promptly to near baseline within 1 h after dialysis. During 3 weeks of dialysis using acetate + lactate, predialysis plasma bicarbonate values were similar to those achieved when using acetate, but with acetate + lactate, the intradialytic plasma acetate levels were reduced by 50%. The results suggest that DL-lactate merits further evaluation as a potential base for hemodialysis solutions, and that both the D- and the L-lactate isomers are metabolized in maintenance hemodialysis patients. PMID- 3326411 TI - Long-standing spontaneous clinical remission and glomerular improvement in primary IgA nephropathy (Berger's disease). AB - Of the 244 cases of IgA nephropathy diagnosed at Necker Hospital before 1981, 9 patients (3.7%) developed spontaneous clinical remission of long duration. Three of these 9 patients presented with gross hematuria, while in the others the disease was discovered by the finding of proteinuria at routine urinalysis. During the disease course 5 patients had recurrent episodes of gross hematuria, lasting several years in 4. At the time of the first biopsy all patients had hematuria and permanent proteinuria. In 1 patient, renal biopsy showed only an increase in mesangial matrix while in the others segmentary lesions were observed, affecting less than 30% of the glomeruli in 6. Diffuse mesangial deposits of IgA were present in all. During the follow-up, proteinuria and microscopic hematuria gradually decreased and completely disappeared within 4-14 years after the onset of the disease. A repeat biopsy performed during remission in 4 patients showed, in 3, an improvement of glomerular lesions and a significant decrease in IgA mesangial deposits in parallel with clinical recovery. As in other types of 'primary' glomerulonephritis, these data indicate that the initial disorder in IgA nephropathy may be spontaneously reversible even after a long course of the disease. PMID- 3326413 TI - [Developmental defects of the uterus and their surgical correction to restore reproductive function]. PMID- 3326412 TI - Hypocomplementemic glomerulonephritis in an infant and mother. Evidence for an abnormal form of C3. AB - A mother developed hematuria during the fourth month of pregnancy, and her nursing infant son from this otherwise uncomplicated pregnancy developed hematuria at 3.5 months of age. Both had a mild glomerulonephritis characterized by mesangial prominence, focal thickening and mottling of the glomerular basement membrane and electron-dense deposits, predominantly in the intramembranous and subendothelial positions. Immunofluorescence studies revealed striking accumulations of C3 and other complement components associated with alternative complement pathway activation within glomeruli, and the presence of small or equivocal amounts of immunoglobulin. C1q, C4 and factor B were not detectable. The glomerular lesion was accompanied by hypocomplementemia. Sera of both mother and infant displayed half normal levels of C3 and factor B, increased levels of C4, and normal levels of 12 other complement proteins. High normal or slight elevation in nephritic factor-like activity was observed in serial serum samples. Studies suggested that this mother and son represent the second kindred having an abnormal form of C3 which produces an alternative complement pathway C3 convertase, C3b, Bb, resistant to control by factor H. No additional affected family members were identified. The course of the nephritis over 7 years without drug therapy has been mild with resolving hematuria and no abnormal proteinuria or decrease in creatinine clearance. PMID- 3326414 TI - [Comparative effectiveness of various immunocorrective drugs in chronic salpingo oophoritis]. PMID- 3326415 TI - [Current methods of treatment of infertility in minor forms of endometriosis]. PMID- 3326416 TI - [Obstetrics in Russia on the eve of the Great October Socialist Revolution]. PMID- 3326417 TI - [Current methods of specific therapy of candidiasis of the urogenital system in women]. PMID- 3326418 TI - Treatment of acute lymphoblastic leukemia in children with the BFM protocol. A cooperative pilot study. AB - From January 1981 through July 1983, 141 children with newly diagnosed acute lymphoblastic leukemia were registered in a cooperative clinical study whose objective was to evaluate the toxicity and the feasibility of the German Berlin Frankfort-Munster (BFM) protocol. The results were comparable with those reported by the BFM group. For the 133 patients (94%) who achieved complete remission, the actuarial disease-free survival was 67% at 4 years. These results were obtained in spite of a high rate of deaths in complete remission during the initial year of the study. Subsequently, probably as a result of improved expertise in the handling of the protocol, the proportion of toxic deaths declined sharply. Although the current BFM protocol adjusts for aggressiveness of therapy according to the volume of the liver and spleen, splenomegaly (but not hepatomegaly) remained of prognostic significance. Moreover, for patients with bad risk features, an initial high hemoglobin level was found to represent an additional factor of negative significance. PMID- 3326419 TI - Haploidentical bone marrow transplantation for osteopetrosis. AB - HLA-matched bone marrow transplantation is an effective form of treatment for some patients with malignant osteopetrosis, a defect of osteoclast function. Following transplant, normal osteoclasts differentiate from donor-derived marrow stem cells and can function normally in some of these patients. For patients without an HLA-matched marrow donor, pharmacologic treatments have not yet proved effective. This article demonstrates that normal osteoclast function can be obtained following the transplantation of HLA-nonidentical marrow that has been purged of T lymphocytes in vitro. PMID- 3326421 TI - History of Medicine in Alaska. J. Ray Langdon, M.D. PMID- 3326422 TI - Glimpses of Alaskan medical history. A frustrated doctor at the Shumagin Islands (1741). PMID- 3326420 TI - Treatment of non-Hodgkin's lymphoma in Mexican children. The effectiveness of chemotherapy during malnutrition. AB - The histological diagnosis of non-Hodgkin's lymphoma (Burkitt's lymphoma excluded) in 147 children was reviewed. The most common site of presentation was in the abdomen (32.6%). The most frequent site of metastatic disease at diagnosis was the bone marrow (27.2%). The most common histology was diffuse undifferentiated non-Burkitt type (37.4%). According to the Murphy staging system, 40.1% were stage III and 27.2% were stage IV. In a nonrandomized prospective study, 121 patients were submitted to a treatment regimen (protocol 8001) and compared with 26 historical controls treated with the COP regimen, consisting of cyclophosphamide, vincristine, and prednisone. Of those patients treated with protocol 8001, nine had intestinal perforation at the site of primary disease. All patients in this group were malnourished at the time of perforation. The overall rate of initial complete remission in those patients treated with protocol 8001 was 90.7%. The duration of remission was from 16 to 108 months, with a median of 39 months. The actuarial rate of disease-free survival was 69% at 2 years and 63% at 6 years, compared with 36% at 6 years of the control group (COP) (p less than 0.01). None of the patients have relapsed after 4 years. PMID- 3326423 TI - [Transdermal scopolamine or droperidol in the prevention of postoperative nausea and vomiting in cholecystectomy patients]. AB - Scopolamine, applicable without severe side effects as a transdermal therapeutic system (TTS), has a pronounced postoperative antiemetic effect. In one publication there was found even a 50% reduction of emetic symptoms compared with placebo. In this study TTS-Scopolamine was compared with a single dose of 7.5 mg Droperidol in a group of 40 Patients undergoing cholecystectomy under standardised balanced anesthesia. After cholecystectomy patients are very much inclined for postoperative nausea and vomiting since it is an abdominal operation and it is more often necessary in women than in men. In this randomized, one-side blind study the antinausea and antiemetic effect of transdermal Scopolamine was insufficient and significantly less than with Droperidol. In the Droperidol-group there were 45% of patients without emetic symptoms, in the Scopolamine-group only 15%. Vomiting occurred in 25% of patients in the Droperidol-group and in 50% of patients in the Scopolamine-group. Unfavourable CNS-side-effects could not be found either with transdermal scopolamine or with Droperidol. As favourable side effects there was found a more even postoperative blood-pressure-curve in the Droperidol-group and a better scoring of preoperative sleep in the Scopolamine group. Overall there is need for an exact indication for transdermal Scopolamine as a postoperative antiemetic. In this study Droperidol turned out to be a much stronger antiemetic for patients undergoing cholecystectomy. PMID- 3326424 TI - [Elimination of drugs by hemofiltration. Principles and literature data]. AB - The elimination of substances during hemofiltration depends on the special properties of the used wide-porous membranes. High filtration-fractions are achieved and, in practice, all substances with a molecular weight below 10,000 Dalton pass the membrane. Also drugs are filtrated equivalent to their unbound free plasma-fraction. A quantitative elimination of drugs during hemofiltration is to expect, 1. if a sufficient ultrafiltration rate of 10 ml/min or more is reached, which is the upper limit of spontaneous CAVH, 2. if the sieving coefficient or plasma-protein-binding enables a sufficient passage and 3. if the serum concentration of the drug related to its administered dose is high, i.e. the volume of distribution is small. An adjustment of drugs is partially necessary during hemofiltration. A simple way is to calculate the total creatinine-clearance to derive dosage modifications. PMID- 3326425 TI - Index issue: Cumulative indexes for Volumes 128-167, 1983-1987. PMID- 3326426 TI - Analytical approaches involving recombinant DNA techniques in the diagnosis of human genetic disorders. A review. PMID- 3326427 TI - [The history of congenital malformations with special reference to conjoined twins. 2. The 18th to the 20th centuries]. AB - Thoughts concerning teratology became increasingly scientific in the 18th century, and research into congenital malformations received a considerable impetus through discoveries concerning early embryonic development. The term "teratology" was coined in the 19th century and the introduction of photography enabled truly objective illustrations. Animal experiments were carried out to an increasing extent, the work of Roux and Speman being particularly notable. The great interest in teratological research in the 20th century was stimulated by observation of the effects of viral infection, radioactivity, thalidomide and diosin on embryonal development. This has led to the current major research capacity available to identify the causes of congenital malformation and to prevent them. PMID- 3326428 TI - [Experiences with reduced formalin fixation of specimens and formalin-free preservation of anatomic samples]. PMID- 3326429 TI - The treatment of trigeminal neuralgia. AB - The etiology of trigeminal neuralgia has yet to be elucidated. Thus it is not surprising that no ideal treatment is currently available. The current treatment of choice is medical; Pharmacologic management should be tried to its fullest extent. Increasing dosages and using combination drug therapies are recommended before considering a surgical approach. If drug therapy does not alleviate the pain, a surgical approach may be indicated, although 100% effectivity is not expected. Until the true etiology of trigeminal neuralgia is established, controversy will remain in the treatment of this complex disorder. PMID- 3326430 TI - Respiratory monitoring for anesthesia and sedation. AB - This article reviews the theory and practice of routine respiratory monitoring during anesthesia and sedation. Oxygen monitoring and capnography methods are reviewed. The current ventilation monitoring system of choice is considered a combination of the pulse oximeter and capnography. Guidelines are provided for monitoring standards. PMID- 3326431 TI - The role of research in pain control for dentistry. PMID- 3326432 TI - Nosocomial bacterial pneumonia: an overview. AB - Nosocomial pneumonia accounts for 10% to 20% of all nosocomial infections and represents one of the most serious complications of hospitalization. This review focuses on the etiology, pathogenesis, and prevention of nosocomial pneumonia, with emphasis on infection control procedures to prevent and minimize its occurrence. PMID- 3326434 TI - Comparing HEp-2 cell line with rat liver in routine screening test for antinuclear and antinucleolar autoantibodies in autoimmune diseases. AB - The comparative study of the human tumor cell line HEp-2 and rat liver for the detection of antinuclear and antinucleolar autoantibodies by the indirect immunofluorescence technic in routine screening test demonstrate that, taking titer and staining pattern into account, both substrates are able to separate autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, scleroderma and primary biliary cirrhosis) patients from healthy subjects. The minimal screening test must include sera diluted 1:20 and 1:80. The capability of the HEp-2 substrate to reveal and to discriminate different speckled nuclear and nucleolar patterns explain its greater performance, notably in detecting anticentromere antibodies highly specific for the CREST syndrome and a speckled nuclear antibody frequently associated with primary biliary cirrhosis, allowing an earlier diagnosis of autoimmune diseases presenting these patterns. PMID- 3326435 TI - Problems of quantitative urine analysis. AB - Quantitative determinations of various analytes in urine represent only a small part of all analyses performed in the routine clinical chemistry laboratory. Consequently, analytical as well as pre-analytical problems are less often considered in urine analysis. In the first part of this paper, pre-analytical factors affecting quantitative determinations are discussed, e.g., physical activity, posture, circadian rhythms, different solubilities of the various substances, errors in urine collecting, or drug effects. Subsequently, aspects of linearity and specificity of the routine determinations will be illustrated with special consideration given to protein, calcium, and enzyme determinations as well as some specialized measurements, e.g., porphyrins, catecholamines and their metabolites, or 5-hydroxyindole-acetic acid. Effects of pre-analytical and analytical factors on intra-assay and between-assay variations found in urine analysis are discussed. Using the results of surveys, it is shown that the standardization of methods as well as the use of suitable standards are mandatory for an effective amelioration of the present quality of quantitative urine analysis. PMID- 3326436 TI - [Does the fibrinogen-fixing factor of Candida albicans play a role in the physiopathology of candidiasis?]. PMID- 3326433 TI - Draft guideline for use of topical antimicrobial agents. PMID- 3326438 TI - [5-Fluorocytosine and combinations]. AB - The antimycotic and pharmacological properties of 5-fluorocytosine are presented. Especially the aspect of good gastrointestinal absorption, elimination by the kidney, unwanted side effects and appearance of primary and secondary resistance are discussed. The indication of 5 FC monotherapy or combination therapy is shown in various manifestations of deep candidiasis. PMID- 3326437 TI - [Local production of specific antibodies in the aqueous humor in experimental Candida endophthalmia in rabbits]. AB - An increasing frequency of ocular lesions due to Candida albicans has been reported, but clinical detection of lesions, which may cause permanent blindness, remains difficult. Hematogenous endophthalmitis caused by Candida albicans in the rabbit is a useful model to study the pathogenesis of the disease, and perhaps to find new methods of biological diagnosis. A suspension of Candida albicans was injected in 15 rabbits, according to the method described by Edwards et al. In 1975, causing uni or bilateral chorioretinitis in 12 of them. Unaffected eyes were chosen as controls. After aspiration of the anterior chamber fluid, serum and aqueous humour titres of specific antibodies were determined. A local synthesis of IgG antibodies was detected, after comparison of the titres of specific antibodies in the aqueous humour and in the serum, related to the serum and aqueous humour concentrations of IgG antibodies. According to a formula proposed by Witmer and Desmonts in ocular lesions due to different pathological agents, we calculated the "C" coefficient: C = antibody titres aqueous humor/serum x IgG serum/aqueous humor. A local synthesis of specific antibodies in cases of experimental endophthalmitis leads us to believe that aqueous humour aspiration could be used in the diagnosis of endophthalmitis in humans. PMID- 3326440 TI - [Optimization of sensitivity tests to ketoconazole. Value of experience planning in the choice of a medium]. AB - Using factorial design, the authors evaluate the factors which influence in vitro, the anti-fungal activity of ketoconazole against a strain of Candida albicans (CBS 562). With the four mediums most frequently used, (Sabouraud, Casitone, MEM, YNB) they precise the results concerning inoculum, pH, incubation temperature, growth time, serum concentration, and shaking. This method allows the evaluation of each factor in optimal conditions of test. In most cases, the best results are obtained with a 10(4) UFC/ml inoculum, a pH = 7, in absence of serum and without shaking. The influence of temperature is very small. In these conditions, the Casitone medium seems the most satisfactory. PMID- 3326439 TI - [Current role of amphotericin B in the treatment of deep mycoses]. AB - Amphotericin B (Am. B), a polyene heptaene, is an antifungal antibiotic substance produced by Streptomyces nodosus, a telluric actinomycetal from Venezuela. Although it is a very toxic substance and its pharmacokinetic is not completely known, Am. B is yet the former antifungal substance utilised against number of pathogenic agents of systemic mycoses. Am. B binds irreversibly to sterols of fungal cytoplasmic membranes causing a leak of potassium and other impairments leading the fungal cell to death. Further, Am. B might to induce an enhancement of humoral and cellular immunity. After intravenous perfusion, 95 per cent of Am. B binds to plasma lipoproteins. Only a low proportion of the Am. B serum level is detected in the CSF. Distribution of Am. B to extravascular inflammatory fluids and secretions might be letter. Am. B might be eliminated essentially by biliary way. Am. B toxic effects are very frequent. Generalized reactions are observed to the earlier doses. Toxic visceral, above all, nephrotoxic manifestations, appearing later. Recent results, from experimental and human infections suggest that Am. B encapsulated in liposomal vesicles is more active, less toxic and more easily administered. PMID- 3326441 TI - [Prevention of nephrotoxicity of amphotericin B during the treatment of deep candidiasis]. AB - Previous observations suggest that tubulo-glomerular feedback could be involved in amphotericin B nephrotoxicity. We then investigated the influence of sodium status on the occurrence of renal damage during amphotericin B therapy. A retrospective survey demonstrated that impaired renal function occurred during therapy in 67 per cent of the patients who received amphotericin B alone and in 12 per cent of the patients who received amphotericin B and ticarcillin (parenteral sodium supplement of 100-150 meq per day). Prospective studies were then undertaken both in adults and children. Intravenous sodium supplement was given intravenously as routine prophylaxis with amphotericin B therapy. In all courses amphotericin B was successfully administered without deterioration in renal function. These results support the hypothesis that parenteral sodium supplementation reduces the frequency of developing impaired renal function during amphotericin B therapy. PMID- 3326442 TI - [Treatment of acute leukemia. Current status and perspectives]. PMID- 3326443 TI - [Biological significance of the endogenous secretion of insulin in response to breakfast in diabetic children]. AB - In 20 insulin dependent diabetics and in eight age-matched healthy children, we have measured basally HbA1 and the plasma lipid profile; and both basally and after a standard breakfast of 400 cal, blood glucose, C-peptide (CPR), immunoreactive glucagon (IRG), growth hormone and nonesterified fatty acids (NEFA). No difference was found in the lipid profile of diabetic and non diabetic children. In diabetics basal blood glucose was significantly correlated to both basal C-peptide (r = 0.5332, p less than 0.05) and to the ratio C peptide/glucagon (r = 0.8563, p less than 0.01). The C-peptide response to the breakfast was accompanied of a significant increase in IRG and NEFA in diabetics, while in non-diabetics there was no change in IRG and a significant decrease in NEFA levels. Diabetic children with basal C-peptide levels higher than 0.6 ng/ml had lower blood glucose levels (187 +/- 43 vs 315 +/- 20 mg/dl, p less than 0.02), but no difference in blood glucose or any other parameter was observed as a function of the increase in CPR after breakfast. From these results we conclude that the evaluation of residual B-cell function in diabetic children by measuring the C-peptide response to a provocative stimulus is not more informative than the single basal measurement of C-peptide and does not have an additional biological significance, at least in hyperglycaemic insulin dependent diabetic children. PMID- 3326444 TI - [Semilobar holoprosencephaly associated with central diabetes insipidus]. AB - The clinical and neuroradiological findings in a case of semilobar holoprosencephaly associated to hypernatremia behaving like diabetes insipidus are described. The differential diagnosis with a neurogenic hypernatremia is discussed. The advantages of ultrasounds in the diagnosis of this malformation are pointed out. So are the characteristics which differentiate it from other neurological malformations and the importance of a dorsal sac to delimitate the more serous clinical forms. PMID- 3326445 TI - [Idiopathic perforation of the choledocus in childhood]. AB - The purpose of this report is to describe a seven-years-old patient with an idiopathic perforation of the common bile duct. This disorder is more frequent in the first weeks of life, and the clinical features are not well known. Properly treated, the majority of infants survive without sequelae. Furthermore, a review of the literature is made. PMID- 3326446 TI - [General therapy of acute poisoning in primary care]. PMID- 3326447 TI - [Traumatic lesions of the liver: clinical review of 50 cases]. PMID- 3326448 TI - [Surgical indications in solitary thyroid nodules]. PMID- 3326449 TI - [The artificial pancreas as an adjuvant method in a surgical environment. Indications and field of action]. PMID- 3326450 TI - [Can diabetic nephropathy be prevented? Or what is the point of no return?]. PMID- 3326451 TI - [Polyneuropathy and solitary bone plasmacytoma. A new case]. AB - The authors report a case of acute polyneuropathy revealing a solitary osseous plasmacytoma with osteo-dense and osteolytic bone lesions. Initially, the rapid progression of the sensory and motor loss led to treatment by plasma exchanges and irradiation of the plasmacytoma. Four months later, despite a significant improvement of the neurological condition, serum protein electrophoresis continued to show a peak of monoclonal immunoglobulin. Chemotherapy with cyclophosphamide and prednisone was administered for one year whilst the neuropathy continued to regress. This case, which presents many classical features of plasma cell dyscrasia (polyneuropathy with albumino-cytological dissociation, radiological osseous condensation, low concentrations of lambda light chain protein), illustrates some unusual features of solitary plasmacytomas associated with peripheral neuropathy: the young age of our patient, an acute progression of the neuropathy in the early stages, tumoral localisation in the diaphysis of a long bone. PMID- 3326452 TI - [Lymphoblastic leukemia and immunological markers]. AB - Acute lymphoblastic leukemia (ALL) is a heterogeneous entity that can be subcategorized on the basis of morphologic aspects, membrane antigens, caryotypic analysis and enzymatic content of the blast cells. Subgroups corresponding to T cells, Band pre-B cells, and non T non B lymphocytes derivations can be defined by immunologic markers. These studies ease the diagnosis and characterisation of ALL, perhaps their treatment, and enhance understanding of the disease. PMID- 3326453 TI - [Incipient diabetic nephropathy]. PMID- 3326454 TI - 13C and 31P NMR studies of hepatic metabolism in two experimental models of diabetes. PMID- 3326455 TI - Nuclear magnetic resonance spectroscopy in the cancer clinic. PMID- 3326456 TI - Monitoring cancer therapy by NMR spectroscopy. PMID- 3326457 TI - NMR spectroscopy for clinical medicine. Animal models and clinical examples. AB - Magnetic resonance spectroscopy is able to measure noninvasively a variety of important metabolites involved in cell energetics. These include phosphocreatine, ATP, inorganic phosphate, pH, and lactate. Anoxia, ischemia, and infarction produce rapid loss of high-energy phosphates and accumulation of hydrolysis products. Many animal studies have shown that MRS monitors metabolic changes in various models of human disease. The availability of large, high field magnets and the development of noninvasive localization techniques permits MRS to be performed on selected volumes within the body. It is now clear that MRS in humans will be immediately useful in several areas including studies of malignancy, ischemia, and infarction of various organs and metabolic disorders. It is expected that human MRS will be increasingly used for clinical investigation and eventually for medical diagnosis. PMID- 3326458 TI - The biochemistry of human diseases as studied by 31P NMR in man and animal models. PMID- 3326459 TI - Spatial localization in NMR spectroscopy in vivo. AB - Spatial localization techniques are necessary for in vivo NMR spectroscopy involving heterogeneous organisms. Localization by surface coil NMR detection alone is generally inadequate for deep-lying organs due to contaminating signals from intervening surface tissues. However, localization to preselected planar volumes can be accomplished using a single selective excitation pulse in the presence of a pulsed magnetic field gradient, yielding depth-resolved surface coil spectra (DRESS). Within selected planes, DRESS are spatially restricted by the surface coil sensitivity profiles to disk-shaped volumes whose radii increase with depth, notwithstanding variations in the NMR signal density distribution. Nevertheless, DRESS is a simple and versatile localization procedure that is readily adaptable to spectral relaxation time measurements by adding inversion or spin-echo refocusing pulses or to in vivo solvent-suppressed spectroscopy of proton (1H) metabolites using a combination of chemical-selective RF pulses. Also, the spatial information gathering efficiency of the technique can be improved to provide simultaneous acquisition of spectra from multiple volumes by interleaving excitation of adjacent planes within the normal relaxation recovery period. The spatial selectivity can be improved by adding additional selective excitation spin-echo refocusing pulses to achieve full, three-dimensional point resolved spectroscopy (PRESS) in a single excitation sequence. Alternatively, for samples with short spin-spin relaxation times, DRESS can be combined with other localization schemes, such as image-selected in vivo spectroscopy (ISIS), to provide complete gradient controlled three-dimensional localization with a reduced number of sequence cycles. PMID- 3326460 TI - NMR microscopic studies of eyes and tumors with histological correlation. PMID- 3326461 TI - NMR investigations of cellular energy metabolism. PMID- 3326462 TI - Hematopoietic growth factors as therapeutic agents. PMID- 3326464 TI - Molecular mechanisms of chromosome translocation in human B- and T-cell neoplasia. AB - Our understanding of the molecular biology of many tumors is still rudimentary. The genes involved in most solid tumors, and the mechanisms giving rise to their activation, are virtually unknown. In contrast, for hematopoietic malignancies, we have identified several genes important in oncogenesis, and we understand in at least a limited sense the mechanisms by which translocations impart these genes with the capacity to support malignant growth. It is becoming increasingly apparent that these mechanisms involve very subtle changes in the pattern of gene expression. Similarly, the studies on the mechanisms of chromosome translocation described here underscore the proposition that malignancy may arise by slight perturbations of normal function. The enzymes that physiologically recombine Ig and TCR genes do so with high fidelity under normal circumstances. But occasionally misrecognition of target sequences may lead to chromosome translocation and neoplasia. A deeper understanding of this process will be facilitated by a more certain grasp of normal B- and T-lymphocyte differentiation and proliferation. PMID- 3326463 TI - Interactions of retroviral and cellular transforming genes with hematopoietic cells. PMID- 3326465 TI - Mechanism of activation of the myb oncogene in myeloid leukemias. PMID- 3326467 TI - Comparison of oncogene expression in human normal bone marrow and leukemia. PMID- 3326466 TI - Induction of transformed cells to terminal differentiation. AB - HMBA induces MEL cells to terminal erythroid differentiation. HMBA causes a decrease in diacylglycerol concentration, a decrease in Ca+2 and phospholipid dependent protein kinase C activity (within 2 hr). There is an early (within 1-2 hrs) suppression of c-myb and c-myc gene transcription and an increase in c-fos mRNA (within 4 hrs). During the early or "latent" period there is no detectable commitment of MELC to terminal cell division or expression of differentiated genes such as alpha 1 or beta maj globin genes. HMBA-induced commitment to terminal differentiation is detected by 12 hrs and over 95% become committed cells by 48-60 hrs. Commitment is associated with persistent suppression of c-myb gene transcription and elevated levels of c-fos mRNA, whereas the level of c-myc mRNA returns to that of uninduced cells. By 36-48 hrs, transcription of the alpha 1 and beta maj globin genes increases 10-30 fold, and that of rRNA genes is suppressed. Changes in expression of c-myb, c-myc, c-fos and p53 genes that occur early during HMBA-induced differentiation may be important in the multistep process involved in commitment of MEL cells to terminal differentiation. Continued suppression of c-myb gene expression may be required for terminal differentiation of these cells. PMID- 3326468 TI - C-myc gene effects on cell growth and transformation. PMID- 3326469 TI - A novel type of c-myc translocation in a T lymphoma cell line. PMID- 3326470 TI - Tumor promoters enhance v-myc-induced focus formation in mammalian cell lines. PMID- 3326471 TI - Early hemopoietic differentiation: the action of multi-CSF is complemented by lineage specific growth factors. AB - Although mechanisms controlling differentiation of hemopoietic stem and early progenitor cells are still poorly understood, it is generally conceded that a pivotal role is played by hemopoietic growth factors (HGFs). However, in-vitro analysis of their action on early progenitors may be obscured by cell-cell interaction, as well as by the presence of fetal bovine serum (FBS). To overcome these limitations, we investigated the action of pure multipotent or lineage specific HGFs on purified progenitors grown in FBS-free cultures. In the murine system, highly purified progenitors were cultured in the presence of multipotent colony-stimulating factor (multi-CSF, also termed interleukin-3), erythropoietin (Ep) and macrophagic-CSF (M-CSF). Each HGF was unable by itself to induce significant colony growth. However, combined addition of multi-CSF and either Ep or M-CSF gave rise only to pure erythroid or macrophagic colonies, respectively. Partly purified human progenitors were challenged by human granulomonocytic-CSF (GM-CSF), pluripotent CSF (PPO, also termed granulocytic-CSF, G-CSF) and Ep. Here again, each HGF was unable per se to promote colony growth, but combined addition of GM-CSF or PPO and Ep gave rise only to pure erythroid colonies. These results support a model of early hemopoietic differentiation according to which multi lineage HGFs represent "competence" GFs, the action of which is complemented by lineage-specific "progression" HGFs. PMID- 3326472 TI - Sequential pilot studies of intensive postremission chemotherapy for acute nonlymphocytic leukemia. PMID- 3326473 TI - The role of residual host immunity in graft failures following T-cell-depleted marrow transplants for leukemia. PMID- 3326474 TI - Clinical problems associated with T cell depletion for bone marrow transplantation. PMID- 3326475 TI - Bone marrow transplantation in thalassemia after busulphan and cyclophosphamide. Report on 88 cases. PMID- 3326476 TI - The role of autologous bone marrow transplantation in acute leukemia. AB - One hundred and twenty-seven patients with acute leukemia were treated with high dose cytoreductive programs in conjunction with autologous marrow. Transplantation in relapse resulted in a complete remission rate ranging from 33% to 72%, depending on the time of transplantation, the conditioning regimen used and the performance status of the patient. Remission duration was short, ranging from three to nine months. Transplantation in second or subsequent remission did not change the natural history of the disease. In 14% of the cases, transplantation remissions were obtained exceeding the duration of the preceding remission, results equivalent to those obtained by normal dose chemotherapy. Transplantation in first remission (CR1) resulted in a projected two-year disease free survival of 72% (13% SE) in acute myelogenous leukemia and of 45% (17% SE) in acute lymphocytic leukemia. We conclude from these data that the results look promising in CR1 and that in second and subsequent remissions a realistic study design is possible by which the influence on the natural history of disease by changing the bone marrow transplantation program, such as purging in vitro, can be studied. PMID- 3326478 TI - Molecular cloning and production in microorganisms of hemopoietic growth factors. PMID- 3326477 TI - Autologous bone marrow transplantation for patients with acute myelogenous leukemia in complete remission. PMID- 3326480 TI - Thrombogenic and nonthrombogenic biological surfaces. PMID- 3326479 TI - Hemopoietic cell progenitors in the avian embryo: origin and migrations. PMID- 3326481 TI - Activation of endothelial cells. PMID- 3326483 TI - Adhesion of blood platelets to the extracellular matrix of cultured human endothelial cells. PMID- 3326482 TI - Regulation of platelet-fibrin thrombi on subendothelium. PMID- 3326484 TI - Cells and aggregates at surfaces. PMID- 3326485 TI - Video microscopic and immunochemical evaluation of cells at surfaces. PMID- 3326486 TI - Methods of assessment of thrombosis in vivo. AB - The contributions of platelets and clotting factors in thrombosis on injured vessel and cardiovascular prostheses have been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and humans with 111In-labeled platelets, 123I- and 131I-labeled fibrinogen, 111In labeled antibody to the fibrinogen receptor on the platelet membrane and to fibrin. Thrombus localization by imaging was possible for large thrombus in vessel with deep injury of thrombogenic surface in the acute phase. A single layer of adherent platelet could not be imaged, due to the high background radioactivity present in blood. Thrombogenicity of graft was compared with that of contralateral vessel. The dynamic process of platelet deposition could be followed accurately using the in vivo imaging technique. In addition, in vitro quantification permits determination of platelet and fibrin density and of the number of fibrin monomers per platelet in thrombus. The roles of prostacyclin, thromboxane inhibitors, and nonsteroidal antiinflammatory drugs have also been evaluated in animals models and humans. The tracer techniques thus provide invaluable information about platelet-fibrin deposition, its organization and dissolution, and for development of less thrombogenic surfaces for use in cardiovascular prostheses. PMID- 3326487 TI - Methods of assessment of thrombosis ex vivo. PMID- 3326488 TI - Evolution of thrombosis. PMID- 3326489 TI - Animal models for the evolution of thrombotic disease. AB - Naturally occurring hemorrhagic and thrombotic diseases of animals closely parallel their human counterparts. While such models may be particularly useful in studying the pathogenesis of human disease, it is usually more realistic to depend upon experimentally induced disease models. The species selected for use is therefore of major importance in providing meaningful extrapolation to humans, as are the experimental design and type of procedure (in vitro, ex vivo, in vivo). Regardless of the test system used when in vitro procedures are employed, these must be translated eventually to the in vivo situation. Information about the normal aging process of different species is important here and should influence selection of the species and test system. The ideal situation may not be feasible or pertain because of cost, availability, size, and investigator familiarity, or lack thereof, with the most suitable species or model. PMID- 3326490 TI - Selected methods of investigation for blood-contact surfaces. AB - It is imperative that operating personnel and regulatory agencies have secure, advance, and accurate knowledge of the true surface properties of materials to be contacted with flowing blood. The actual devices must be characterized in their sterile, immediate pre-exposure states. Although very sensitive electronic instrumental analysis techniques are available, the requirements for small specimens exposed to high vacuums and energetic beams hinder their use with practical prosthetic implants. Thus, it remains important that classical estimation of the "wettability" of nonphysiologic materials by simple contact angle measurements can document their real surface qualities in the condition and environment of their intended application. These data, acquired quickly and nondestructively, together with confirming laboratory results from internal reflection infrared spectroscopy, scanning microscopy, and X-ray analysis, are the most useful indicators of material safety and effectiveness for blood contact uses. Experience has shown that the critical surface tensions of materials, determined from contact angle measurements in air rather than underwater, are generally predictive of the tenacity of bioadhesion at their boundaries with blood and other living tissues. Overall, it is now recommended that the surface chemistry of all implant materials be characterized before any exposure to flowing blood, as a minimum requirement of good practice. PMID- 3326491 TI - Influence of endogenous albumin binding on blood-material interactions. AB - A method has been developed to enhance the albumin affinity of a number of medical polymers, based on alkylation of the surface with straight-chain 16- or 18-carbon alkyl groups. This method has been demonstrated to induce the rapid binding of albumin from single and binary protein solutions, from plasma, and apparently, from whole blood. The bound albumin resists fluid shear or chemically induced desorption. Fibrinogen adsorption is inhibited in vitro and in vivo. Complement protein C3 activation from plasma is inhibited. Fibrin formation and platelet aggregation is inhibited in short-term in vivo experiments. Long-term catheter implant studies suggest that the C18 alkylation is more effective than most, if not all, currently available treatments for the retention of a clean, biocompatible, blood-contacting surface. No data have been obtained to date that conflict with the hypothesis that a renewable albumin layer, so formed, blocks the adsorption or conformational alteration of plasma proteins that otherwise might initiate or participate in various host defenses. PMID- 3326492 TI - Issue dedicated to William Henry Walton, OBE, on the occasion of his 75th birthday and his retirement as Honorary Editor-in-Chief 1972-1987. PMID- 3326493 TI - [The plant cell in vitro: characteristics and utilization]. PMID- 3326494 TI - [Isolation of producing cell strains: exploitation of plant cell variability in vitro]. PMID- 3326495 TI - [Optimization of metabolite production by plant cells in vitro]. PMID- 3326496 TI - [Plant cell culture and metabolite production. Evaluation of production]. PMID- 3326497 TI - [Technology and strategies for production of mass cultures of plant cells]. PMID- 3326498 TI - [In vitro culture of plant cells. Developments and perspectives]. PMID- 3326499 TI - Osseointegrated denture in a vascularized bone transfer: functional jaw reconstruction. AB - Total functional reconstruction of the lower jaw often falls short of ideal goals. While reconstructive techniques are available to close large defects with both hard and soft tissue, the insertion of a prosthetic dental appliance and the return to normal masticatory function are often technically impossible or not even attempted. Presented here is a case report of a patient successfully rehabilitated with a fixed dental appliance supported by jaw fixtures osseointegrated into a vascularized iliac crest mandibular reconstruction. At present, 6 additional patients have had mandibular reconstructions and are in various phases of functional dental rehabilitation. When these data are complete, a series report will be presented for publication. PMID- 3326500 TI - New imaging of cerebral ischaemic lesions. High frequency probes and pulsed Doppler. PMID- 3326501 TI - The value of pulsed Doppler in cerebral haemorrhage of the newborn. PMID- 3326502 TI - Common use of diagnostic imaging for childhood wetting (enuresis): a survey of practicing paediatricians in the Federal Republic of Germany and West Berlin. PMID- 3326503 TI - Evaluation of sub-ureteric Teflon injection as an antireflux procedure. PMID- 3326504 TI - Symptomatic patent urachus in children: the contribution of ultrasound. PMID- 3326505 TI - Ectopic ureterocele in the male. PMID- 3326507 TI - Diagnosis of ovarian cysts in the perinatal period and therapeutic implications (20 cases). PMID- 3326506 TI - Local evaluation of abdominal neuroblastoma stage III and IV: use of US, CT, and 123 I-meta-iodobenzylguanidine (MIBG) scintigraphy. PMID- 3326508 TI - Sonography of the neonatal hip: a dynamic approach. PMID- 3326509 TI - Budd-Chiari syndrome in children: radiologic investigation. PMID- 3326510 TI - Acute intestinal intussusception in children. Contribution of ultrasonography (145 cases). PMID- 3326511 TI - [Splenic parenchymal complications in chronic pancreatitis]. PMID- 3326512 TI - [Management in the case of an echo-free pelvic image]. PMID- 3326513 TI - Salivary gland tumors accessioned from west Africa. PMID- 3326514 TI - Treatment of odontogenic myxoma. Review of the literature and report of three cases. PMID- 3326515 TI - Erupted compound odontoma. Review and report of case. PMID- 3326516 TI - Burkitt's lymphoma. Two cases in treatment. PMID- 3326517 TI - The New York Academy of Dentistry. Fellowship list 1987-88. PMID- 3326518 TI - Graft-versus-host disease. A clinicopathologic review. PMID- 3326519 TI - [Design of a hybrid gene coding for the leader sequence of Bacillus amyloliquefaciens alpha-amylase and for human proinsulin]. AB - The chemically synthesized structure gene of human proinsulin was cloned in E. coli on the secretory vector containing regulatory elements of the Bacillus amyloliquefaciens alpha-amylase gene. The proinsulin gene was inserted by the EcoRI site located immediately after the DNA area encoding the alpha-amylase signal peptide. The E. coli cells transformed by such a plasmid produced hybrid protein consisting of the alpha-amylase signal peptide, five amino acid residues after the gene mating and human proinsulin. For accurate mating of the alpha amylase gene leader sequence and proinsulin gene directed mutagenesis was performed on the filiform phage M13 mp9 with synthetic oligonucleotide. The hybrid gene was transferred to the vector molecule capable of replicating in Bacillus subtilis. It was shown that in the cells of both E. coli and B. subtilis there is synthesized protein interacting by the radio-immunological data with antibodies to porcine insulin, a large portion of immunologically active protein being detected in the periplasmic space of E. coli cells and in the culture fluid of B. subtilis cells which was indicative of proinsulin secretion directed by the alpha-amilase regulatory elements. PMID- 3326520 TI - [Sensitivity to beta-lactam and aminoglycoside antibiotics of clinical Proteus strains as dependent upon on their species classification and the source of their isolation]. AB - Sensitivity of 130 Proteus clinical strains was studied. Among beta-lactam antibiotics cefotaxime showed marked advantages with respect to various Proteus species. All the isolates of Proteus mirabilis were sensitive to cefuroxime. Cefamezin and cephapirin were inferior by their activity to cefotaxime and cefuroxime. They were characterized by close antibacterial activity and almost complete cross resistance. Ampicillin and carbenicillin proved to be the least efficient among the tested beta-lactam antibiotics. Isolates of Proteus vulgaris and Proteus penneri were more resistant to the penicillins and cephalosporins than the cultures of Proteus mirabilis. Sensitivity of separate Proteus species to gentamicin, tobramycin, sisomicin and amikacin was close. No cross resistance to the aminoglycosides was detected. Studies on the effect of different doses of the antibiotics revealed pronounced heterogeneity of Proteus by the feature of sensitivity to the tested antibiotics. The level of the heterogeneity was not the same for separate antibiotics. Cultures of Proteus mirabilis resistant to ampicillin, carbenicillin, cefamezin and cephapirin were more frequent in patients with urogenital infections as compared to patients with intestinal infections and suppurative-inflammatory processes of other localization. PMID- 3326521 TI - [Cellular immunity and enzyme activity of xenobiotic metabolism in the lymphocytes of normal minipigs and in alcohol and anabol exposures]. AB - Immunological indices and activity of xenobiotic metabolism enzymes in lymphocytes were studied on minipigs under normal conditions, under conditions of chronic alcoholic intoxication and after administration of anabol (an immunomodulator) to normal healthy animals and to animals with alcohol intoxication. Age-related differences with respect to the number of T-lymphocytes and activity of lymphocyte glutathione S-transferase were observed in the normal animals, the other indices such as activity of natural killer cells, K-cells, blast cell transformation with concanavalin A and activity of cytochrome c reductase being independent of the age. Administration of anabol to healthy animals did not alter their immunoenzymatic status. Chronic alcohol intoxication was accompanied by development of secondary immune deficiency characterized by lower immunological indices and lower activity of xenobiotic metabolism enzymes in lymphocytes. Daily exposure to 0.8 g of anabol for 12 days at this background resulted in normalization of the above indices. PMID- 3326522 TI - [New semisynthetic and natural cephalosporins]. PMID- 3326523 TI - [Effect of surface-active substances on carbohydrate metabolism in the producer of oleandomycin]. AB - Activity of glucose-6-phosphate dehydrogenase (I), fructose diphosphate aldolase (II) and succinate dehydrogenase (III) and content of pyruvate (IV) in the mycelium of the oleandomycin-producing organism were studied during increased intensity of the antibiotic synthesis. The increase in the intensity of the antibiotic synthesis was induced by exposure of the spores to a surface active substance, twin-21. After the exposure a rise in the activity of all the three enzymes in the phase of the culture intensive growth was observed. During the antibiotic intensive production the cultures with increased antibiotic production levels were characterized by significantly higher activity of I as compared to the control while the activity levels of II and III were approximately the same. It was shown that concentration of IV in the mycelium during the antibiotic intensive biosynthesis decreased and the decrease was more pronounced after exposure to twin-21. PMID- 3326524 TI - Antifungal susceptibility tests. PMID- 3326525 TI - Pharmacology and toxicity of high-dose ketoconazole. AB - One hundred sixty patients were entered in two multicenter protocols to receive 400 to 2,000 mg of ketoconazole once daily for nonmeningeal or meningeal coccidiodomycosis. For 24 h after administration of all doses, mean concentrations in serum exceeded MICs for Coccidioides immitis (trough concentrations, greater than 1 microgram/ml). Mean peak concentrations occurred 4 to 6 h after administration, ranging from 7 to 17 micrograms/ml for doses of 400 to 2,000 mg. Incremental increases in peak concentrations in serum were greatest at doses of less than or equal to 1,200 mg. To investigate whether long-term therapy altered concentrations in serum, serial data were studied by several methods. The results suggested a trend to increased levels in serum with prolonged therapy, but were not statistically significant. All 168 cerebrospinal fluid (CSF) samples from meningitis patients contained less than or equal to 2.9 micrograms/ml, and only 6 contained greater than 1 microgram/ml. There was no apparent relation between dose, time after dose, site of CSF sampling, or concurrent inflammation and CSF ketoconazole concentration. Neither concentration in serum, toxicity, nor outcome correlated with dose, calculated in milligrams per kilogram at the fixed doses (400-mg increments) under study. Likewise, at the various doses, concentration in serum did not correlate with outcome or toxicity, suggesting that individual drug disposition was not an important factor in outcome or toxicity. Toxicity was reversible, and principal side effects were nausea and vomiting (50%), gynecomastia (21%), decreased libido (13%), alopecia (8%), elevated liver function tests (5%), pruritus (5%), and rash (4%). Gastrointestinal and endocrinologic toxicity were dose related and increased at doses greater than 800 mg. The cumulative percent toxicity requiring discontinuation of drug was 6, 17, 23, and 56% at 400-, 800-, 1,200-, and 1,600 mg doses. Doses of >400 mg are thus markedly more toxic, and efficacy data for nonmeningeal disease have not demonstrated that they are more efficacious. PMID- 3326526 TI - Outer membrane penetration by (2,3)-methylenepenams. AB - The penetration of the Escherichia coli outer membrane by two sterically restricted analogs of penicillin G was determined. The analog corresponding to the "open" conformation of penicillin G penetrated faster than the "closed"-form analog did, and both analogs penetrated faster than penicillin G did. The results suggest that the conformation of the beta-lactam nucleus may affect penetrability via the porin-mediated pathway. PMID- 3326527 TI - In vitro activities of ICI 194008 and ICI 193428, two new cephem antimicrobial agents. AB - The in vitro activities of two new cephem antibiotics, ICI 193428 and ICI 194008, were compared with those of cefpirome, cefotaxime, ceftazidime, and piperacillin. Essentially all strains of the family Enterobacteriaceae were inhibited by both study drugs at concentrations of less than or equal to 4 micrograms/ml. Both new cephems were comparable to ceftazidime against Pseudomonas aeruginosa (MIC for 90% of strains, 8 micrograms/ml) and were the most active agents tested against Pseudomonas maltophilia (MIC for 90% of strains, 16 micrograms/ml). PMID- 3326528 TI - Susceptibility of Nocardia asteroides to new quinolones and beta-lactams. AB - The susceptibility of 31 strains of Nocardia asteroides to various quinolones and beta-lactams, as well as coumermycin, amikacin, and minocycline, was determined by the agar dilution technique. Ciprofloxacin was the most active fluoroquinolone tested on a weight basis, as it inhibited approximately 50% of the isolates at achievable drug levels in serum. Ceftriaxone and cefpirome were the most active cephalosporins in this system with MICs of 8 micrograms/ml for 80% of strains tested. Imipenem, amikacin, and minocycline were the most effective agents tested. PMID- 3326529 TI - [Morphological study of the renal parenchyma (the tubule system and interstitial tissue) of Wistar rats in shock induced by experimental with E. coli infection]. PMID- 3326530 TI - [Uretero-ureteral anastomosis in rats using a horizontal en-U suture]. PMID- 3326531 TI - [Leiomyosarcoma of the inferior vena cava. Contribution of a new case]. PMID- 3326532 TI - [Conservative renal surgery of tumors. Enucleation]. PMID- 3326533 TI - [The urethra of the patient cystectomized for bladder carcinoma: role of total urethrectomy]. PMID- 3326534 TI - [Current treatment of cystine lithiasis]. PMID- 3326535 TI - [A case of epidermoid carcinoma of the prostate]. PMID- 3326536 TI - Associated movements, postural adjustments and synergies: some comments about the history and significance of three motor concepts. AB - Associated movements, postural adjustments and synergies are three motor concepts directly related to each other, although their historical developments have followed relatively independent paths. We show in this study how some notions, often very old, are evolving and become more precise as the number of observations and experimental results increases. We show also how the relationships between these notions and the terms associated with them may vary depending on the historical period and on the authors. The various kinds of muscular activity related to a movement, which are the object of this review, present several aspects, each of them being often described by different terms, which are analyzed. On the other hand we study the various meanings of some terms or expressions, which may correspond to very different aspects of the motor system. The three concepts analyzed have in common a definition from final manifestations (essentially muscular and mechanical) of motor activity. This characteristic is probably due to the lack of enough experimental data to use more refined criteria for definition, like those based upon nervous structures implicated, mechanisms involved or functional significance. The situation may change in the near future, as this field of investigation is now entering a phase of rapid development. PMID- 3326537 TI - [Echocardiographic assessment in the selection of mitral prostheses]. PMID- 3326538 TI - [Mechanical cardiac prostheses: what they are, how they are and how they behave]. PMID- 3326539 TI - [Kindling: from experimental model to psychiatric clinic]. PMID- 3326540 TI - [Glial reaction in 2 cases of Creutzfeld-Jacob disease]. PMID- 3326542 TI - Desmin distribution in the cardiac outflow tract of the chick embryo during aortico-pulmonary septation. AB - The appearance and distribution of desmin, a muscle type intermediate filament, was examined in the truncus arteriosus of the chick embryonic heart during AP septation by an indirect immunofluorescence method. Prior to septation, on the 4th day of incubation, staining with antidesmin antibody was observed in the AP septum anlagen in the distal truncus. No staining with the antibody was detected in the developing tunica media of the great arteries in the distal truncus at this stage. During septation, on the 5th day of incubation, intense staining with the antidesmin antibody was observed in the cell condensation of the AP septum. In the 6-day-old embryo, the staining in the AP septum was reduced, but fluorescence by staining with the antibody was observed in the developing tunica media. No fluorescence was detected in other mesenchymal cells in the truncal swellings. Because of the time of appearance and the localization of antidesmin reactivity in the developing AP septum, it is suggested that muscle-type cells exist in the AP septum, and that these cells may perform an important function in septation. PMID- 3326541 TI - [Primary melanoma of the leptomeninges. An optical and ultrastructural study]. PMID- 3326543 TI - Three-dimensional organization of the connective tissue fibers of the human pancreas: a scanning electron microscopic study of NaOH treated-tissues. AB - A method for scanning electron microscope (SEM) study of reticular fibers in their original shapes and locations is described. This technique was employed to demonstrate the three-dimensional organization of the reticular fibers of the human pancreas. The cellular elements were effectively removed by treatment of the tissue pieces with a 10% aqueous solution of NaOH for 3-4 days at room temperature. Thin layers of the reticular fibers surrounding the acini and ducts formed a three-dimensional interstitial compartment. The reticular fiber sheaths for the blood vessels coursed through the compartment. In the lobule, there were scattered round or oval capsules for the islets of Langerhans. The capsule also consisted of reticular fibers. Within the capsule, reticular fiber sheaths for accommodating islet capillaries, representing the pericapillary spaces, formed a three-dimensionally anastomosing network. The channels for the capillaries ensheathed by the reticular fibers in the islet were continuous with those in the surrounding exocrine pancreas; thus, the insulo-acinar portal system was confirmed to exist in the human pancreas. This study also maintains that the present method is useful for examining the microvascular organization of the islet. PMID- 3326544 TI - Structure of the 0-specific polysaccharide of Proteus mirabilis S 1959. AB - The complete structure of the 0-specific polysaccharide of the strain Proteus mirabilis S 1959, as analyzed by 13C NMR, is presented. Some data demonstrating the significant heterogeneity of the 0-specific chain in the investigated lipopolysaccharide are also described. PMID- 3326545 TI - Effect of outer membrane proteins of Shigella on delayed hypersensitivity in mice to sheep red blood cells. AB - Small doses of outer membrane proteins (OMP) of Shigella flexneri injected intraperitoneally into mice 1 to 3 days before or 3 days after sensitization of animals with sheep erythrocytes were found to increase delayed hypersensitivity as measured by the footpad reaction. In contrast, administration of higher doses of OMP resulted in suppression of hypersensitivity response. Cell transfer experiments showed that the spleen cells from sensitized and OMP treated mice transferred stimulating and suppressing activity to normal recipients. Suppression of hypersensitivity was also observed when recipients were injected with OMP 24 h before they were infused with spleen cells obtained from donor mice sensitized with sheep erythrocytes. PMID- 3326546 TI - Efficacy of a combination of acetylcholinesterase reactivators, HI-6 and obidoxime, against tabun and soman poisoning of mice. AB - The bispyridinium oxime HI-6, 1-((((4-amino-carbonyl)pyridinio)methoxy) methyl)-2 (hydroxyimino)methyl)pyridinium dichloride monohydrate, combined with atropine is an effective treatment for soman (pinacolyl methylphosphonofluoridate) poisoning but is relatively ineffective against tabun (ethyl N-dimethyl phosphoroamidocyanidate) poisoning in mice. This contrasts with those results obtained using the bispyridinium oxime obidoxime[1,1'-(oxy bis(methylene)) bis(4 (hydroxyimino)methyl) pyridinium dibromide]. The purpose of this study was to investigate the efficacy of the combination of HI-6 and obidoxime plus atropine against poisoning by tabun and soman in mice. The combination of ineffective single doses of obidoxime (5 or 10 mg/kg) and HI-6 (25 or 50 mg/kg) improved the treatment of tabun poisoning over either oxime alone. Combinations employing higher concentrations of obidoxime (25 or 50 mg/kg) and HI-6 (100 or 200 mg/kg) resulted in significant toxicity in the absence of organophosphate poisoning. Against soman poisoning the addition of obidoxime to HI-6 did not attenuate the efficacy of HI-6. The half-life of elimination and peak serum concentrations of HI-6 and obidoxime were not altered following administration of the combined injection. Reactivation of tabun-inhibited acetylcholinesterase was found consistently in the diaphragm but not in the brain. Using response surface methods it was possible to estimate the optimal therapy against soman and tabun poisoning (74.5 mg/kg HI-6 + 31.9 mg obidoxime against 1052 microns/kg obidoxime against 390 microns/kg challenge of soman).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3326548 TI - Rem sleep deprivation in an experimental model of Parkinson's disease. AB - Previous investigations have shown that REM sleep deprived (REM SD) rats display an enhanced response to dopamine agonists. This action seems to be mediated through a supersensitivity of dopamine post-synaptic receptors. Accordingly, REM SD was performed on rats with an experimental model of Parkinson's disease. The animals were bilaterally lesioned in the nigrostriatal pathway through a stereotaxically directed electrical current. Seven days after the surgery the animals were REM SD for 72 hours and immediately after the end of this period were observed in an open field for ambulation, rearing, grooming, and latency. In comparison with non-deprived rats there was a significant increase in ambulation and rearing, a response that appeared again after a second REM SD period on day 21th after the surgery. These data of improvement of two parameters of an experimental model of Parkinson's disease suggest that SD may be useful in this condition. PMID- 3326550 TI - [Electroencephalogram before and after hemodialysis, peritoneal dialysis and renal transplantation: study of correlations between background activity and plasma biochemistry]. AB - We report disorganization of background activity in the EEG of 49 patients with chronic renal failure. An electroencephalographic and biochemical study was performed in 20 patients before and after dialysis sessions. We did the same study before and after peritoneal dialysis in 14 patients. We analysed the EEG compared to biochemical blood abnormalities before and after renal transplantation in 15 patients. We observed worsening of the EEG after hemodialysis and peritoneal dialysis and improvement after renal transplantation, suggesting that in our patients the abnormalities in EEG caused by chronic renal failure were reversible. From our results, we found it difficult to establish correlations between the EEG and the biochemical blood abnormalities. However, there is statistical correlation between hypernatremia, improvement of metabolic acidosis, increase of the ratio of zinc to copper and worsening of the background activity in EEG. PMID- 3326549 TI - [High-dose intravenous penicillin therapy in neurosyphilis. III. Evaluation of antitreponemal antibodies of the IgM class in cerebrospinal fluid and serum]. AB - IgM antibodies against Treponema pallidum were investigated in the serum and in the CSF of 9 patients with symptomatic neurosyphilis, before the treatment and in several occasions after the treatment. Tests used were the FTA-Abs test, the IgM solid phase hemadsorption test and an IgM-Elisa test. Titers of reactions decreased after treatment but they were still reactive in the blood and in the CSF during the second year after the treatment. PMID- 3326551 TI - [Central pontine and extrapontine myelinolysis: report of an autopsied case and review of the literature]. AB - An autopsied case of central pontine and extrapontine myelinolysis in a 16-year old diabetic girl is described. Due to dehydration she was treated vigorously with daily intravenous isotonic saline, from the first day of hospitalization. In the first three days the serum sodium level increased by more than 30 mEq/l when compared with the initial level. By the next days the serum sodium level, after a mild drop, rose again and was maintained above normal range for a further 12 days. On the sixth day of this new and sustained serum sodium increase, the patient presented progressive neurological manifestations that remained until her death, characterized by mutism, inability to eat, to move her head, trunk, and members and, in addition, retention of respiratory secretions. The neuropathological examination showed massive central pontine myelinolysis and similar myelinolytic lesions in the subcortical white matter of the temporal lobe, the right optic tract, the external and extreme capsules to the right, the main mammillary tract and the subcortical white matter of the left cerebellar hemisphere. The review of the literature on central pontine and extrapontine myelinolysis shows that the present case is the 30th of such condition. The clinical picture and the etiopathogenesis of central pontine and extrapontine myelinolysis are commented upon. It is suggested, as possible causative factors, the persistent and rapid correction of serum sodium concentration as well as its fluctuation in patients with hyponatremia and/or dehydration. PMID- 3326547 TI - Passively inhaled tobacco smoke: a challenge to toxicology and preventive medicine. AB - The difficulties in defining the exposure of a passive smoker might explain the controversial results regarding an association between passive smoking on one hand and lung cancer, tumors of all sites and ischemic heart diseases on the other. The plausibility of these epidemiological observations will be discussed in the light of analytical, toxicological, biochemical and oncological data. The minute amounts of nicotine and particulate matter, even the much higher concentrations of volatile substances, such as nitrosamines, NOx, acroleine and formaldehyde, present in diluted sidestream compared to mainstream smoke and breathed by involuntarily smoking people, cannot explain their relatively high cancer risk. It is plausible if one considers the high capacity of cigarette smoke to induce drug metabolizing enzymes. Diluted sidestream smoke, however, lacks compounds which induce several iso-enzymes of cyt. P-450 monooxygenase in the tissues. The best evidence is the up to 100-fold increase in placental enzymes if pregnant women smoke, whereas passively inhaled tobacco smoke is ineffective as inducer. The small amounts of paternal smoke inhaled by pregnant women, containing teratogenic and carcinogenic compounds, which are supposedly not detoxified in the placenta, seem to explain the higher risk for malformations of the fetus and the same or even increased risk for perinatal mortality, compared with the outcome of pregnancy if the mother smoked. The induction of placental enzymes very probably protects the fetus against the much higher amounts of toxic agents inhaled by the smoking mother. The increased activity of placental enzymes seems to be a model for the probably greater capacity of certain cyt. P-450 iso-enzymes in the lung and other tissues to convert carcinogens to inactive metabolites when the individual smokes actively. It is well known that concomitant administration of carcinogens with inducing agents inhibits tumor growth in animals because of a shift in the metabolism which favours the formation of ineffective substances. The negligible amounts of nicotine and CO in passively inhaled tobacco smoke cannot be responsible for the surprisingly high risk for ischemic heart diseases of passive smokers. A plausible explanation is offered by experiments with doves and chicken, which develop atherosclerotic lesions due to the action of carcinogens which are metabolized by certain inducible cyt. P-450 iso-enzymes in the aortic wall. Much circumstantial evidence will be presented, indicating that PAHs, contrary to the propagated opinion, play a minor role for the initiation of cancer in active smokers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3326552 TI - [Schistosomiasis of the spinal cord: tumor form. Report of a case]. AB - A case of schistosomiasis of the spinal cord is presented. A 16 years old boy developed a progressive spinal cord compression syndrome suggesting an intramedullary tumor. At the operation a granulomatous mass of the conus and epiconus was found and partially resected. The histopathological examination showed a granulomatous reaction surrounding Schistosoma mansoni eggs. The authors review the various aspects of spinal cord schistosomiasis, particularly the tumoral or granulomatous form. A comprehensive review of the literature is made. PMID- 3326553 TI - Cerebral vasospasm. AB - Cerebral vasospasm is an important component of pathological entities such as migraine, subarachnoid hemorrhage (SAH), head trauma, post cerebral ischemia and/or hypoxia. The mechanisms underlying cerebral vasospasm in these diseases are not completely understood. Neurochemical and morphological factors involved in the cerebral circulation control are reviewed in this article. The circulatory changes observed after subarachnoid hemorrhage are taken as a model. It is concluded that multiple biochemical, physiological and morphological factors are involved in the cerebral vascular responses after SAH. Possible treatment alternatives for cerebral vasospasm based on its etiology are discussed. PMID- 3326554 TI - John P. Merrill Celebration Symposium. October 11-12, 1985, Boston. PMID- 3326555 TI - John Putnam Merrill: an appreciation. PMID- 3326556 TI - About John P. Merrill. PMID- 3326557 TI - J. P. Merrill: a founder of scientific clinical nephrology. PMID- 3326558 TI - Management of the sensitized patient awaiting a cadaver allograft. AB - One of the most difficult problems in renal transplantation, and one that is steadily worsening, is finding acceptable kidneys for the highly sensitized transplant candidate whose antibody level may translate into years of waiting for a cadaver kidney. The causes of such sensitization are well known to be prior allografts, pregnancies, and transfusions. The longer a transplant center has been in existence, the larger is its pool of such highly sensitized patients. Patients who have rejected a previous transplant are a major contributor to this pool, especially when that transplant was poorly matched. Even though rejection losses have been cut from about 50 to 25% since 1973, the dramatic increase in the number of transplants and the sharply lower mortality rate together have led to twice as many patients being returned to waiting lists. As a preventive measure, better human lymphocyte antigen (HLA) matching would help to reduce rejection rates further and, for those that do reject, would lessen their sensitization levels and their waiting time for a second kidney. Measures to diminish the consequences of sensitization have included determining a patient's antibody specificities in order to create a profile of safe donor antigens. Making sensitized patients priority patients and sharing kidneys for them are important measures as well, but the proper definition of a highly sensitized patient requires more than a simple panel reactive antibody (PRA) value. The calculation of the combined probability (pc) of transplantation, based on HLA and ABO gene frequencies, more accurately reflects the true transplantability of a potential recipient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3326559 TI - Renal innervation and denervation: lessons from renal transplantation reconsidered. AB - Renal transplantation assures complete denervation of the kidney. Human renal transplantation provided an opportunity to examine the consequences of renal denervation on renal functional capacity in human subjects. These initial studies led to an anatomical and physiological assessment of the time course of renal neural degeneration and reinnervation following renal transplantation or surgical division of the renal nerves. Together with a growing body of information concerning the extensive intrinsic innervation of the kidney's structural components, there has developed a comprehensive understanding of the overall neural control of kidney function. PMID- 3326560 TI - Pathways for water absorption and physiological role of the lateral interspaces in the kidney tubule. AB - Possible routes for water and salt flow and the most likely theories that describe coupling between water and salt flow across leaky epithelia are presented. The osmotic theories seem the most likely ones. However, several of the theories have weaknesses that render them unsatisfactory, in particular because of the possibility of paracellular water flow in these epithelia. Puzzling are the findings that measurements of the cellular water osmotic permeability give figures that are too low for some of the exclusively transcellular theories to work. If these observations hold in the future, it may be shown that part of the water moves through paracellular pathways in these leaky epithelia. This view is supported by the observation that large extracellular markers are dragged by volume flow. Finally, experimental evidence is reviewed indicating that changes in the luminal area concentration may modulate the functional state of the nephron junctional complexes. PMID- 3326561 TI - Therapeutic application of phenylalanine immunoadsorbent with on-line regeneration. AB - To improve the adsorption capacity of the artificial reticuloendothelial system containing phenylalanine as a ligand, a regeneration method for the adsorbent during plasma perfusion was developed. The adsorbed rheumatoid factor, immunoglobulins, and complements were demonstrated to be elutable from the adsorbent with a 5% glucose solution in vitro. The regeneration method was applied to the treatment of a patient with rheumatoid arthritis. During each plasma perfusion, the adsorbent was regenerated, usually twice, with a 5% glucose solution at a flow rate of 50 ml/min. After each regeneration, the adsorption capacity of the adsorbent was found to be improved by determining the pre- and post-column plasma titers of a rheumatoid arthritis hemagglutination test. PMID- 3326562 TI - Effects of membrane structure on removal of low molecular weight proteins. AB - Much attention is being devoted to the efficient removal of beta 2-microglobulin from patients on hemodialysis as it may cause amyloidosis. The objective of the present article is to clarify the beta 2-microglobulin removal characteristics of dialysis membranes having varying water contents and pore radii. For membranes of regenerated cellulose, polymethylmethacrylate (PMMA) and ethylenevinyl alcohol (EVA), solute and pure water permeability and water content were determined by the standard methods. Data analysis using a tortuous pore model allows determination of pore radius, surface porosity, and tortuosity, and hence, the sieving coefficient as a function of Stokes radius. Based on the tortuous pore model calculation, little beta 2-microglobulin is removed from patients on hemodialysis by regenerated cellulose and PMMA membranes, but EVA membranes, with a sieving coefficient of 0.5, are capable of removing it. The solute permeability for urea is about 2 orders greater than that for beta 2-microglobulin. PMID- 3326564 TI - Animals in surgical research. PMID- 3326563 TI - Immunohistological reaction patterns of cervical lymph nodes in patients with laryngeal carcinomas. AB - An attempt was made to assess the immunological importance of regional lymph node histology in relation to the survival of 107 patients with carcinoma of the larynx, operated on from 1973 to 1982 at the ENT-Clinic in Marburg. A total of 2765 sections of lymph nodes removed during neck dissections were examined microscopically to evaluate the morphological patterns of response. Microscopically, four distinct patterns were defined. Patients whose lymph nodes demonstrated immunological responses according to patterns I and II in the form of either expanded inner cortices or increased numbers of germinal centers had a greater 5-year survival rate than those patients whose lymph nodes showed an unstimulated pattern. Eight patients whose lymph nodes showed a depleted pattern, IV, did not survive more than 3 years. Morphological assessment of immunological activity in lymph nodes draining malignant tumors seems to be of value in predicting survival. The evaluation of the reaction pattern and difficulties in methodology, however, set definite limitations to our study. PMID- 3326565 TI - The 50th George Adlington Syme oration. Hartigan's syndrome. PMID- 3326566 TI - Merkel cell carcinoma: a review of behaviour patterns and management strategies. AB - Eleven patients with Merkel cell carcinoma of the skin were reviewed retrospectively. The aggressive nature of this tumour is reflected by the incidence of local recurrence, regional nodal metastases and systemic dissemination, which is 36%, 55%, and 18% respectively. This high frequency of local recurrence and metastases is confirmed in the literature. Management strategies should be planned accordingly, following accurate assessment of the extent of disease. Wide excision, with or without nodal dissection, together with adjuvant wide field irradiation is necessary for loco-regional control of this radiosensitive tumour. Radiotherapy alone may be appropriate treatment for extensive loco-regional tumours or in those that have already metastasized. Although the role of chemotherapy is unclear, there are an increasing number of reports of chemosensitivity and further investigation in this area is required. PMID- 3326567 TI - The use of an iodophor-impregnated plastic incise drape in abdominal surgery--a controlled clinical trial. AB - A prospective randomized clinical trial comparing the use of a new iodophor impregnated incise drape with a standard skin preparation technique in 1102 patients undergoing abdominal surgical procedures is reported. The effect of the incise drape on wound bacterial contamination and subsequent wound infections is compared. The iodophor-impregnated plastic incise drape reduced the contamination of the wound. In particular, isolates of normal skin organisms were less frequent when the drape was used in clean and clean contaminated procedures. However, no difference was found between the wound infection rates for the patients on whom the iodophor drape was used and those patients on whom the drape was not used. PMID- 3326568 TI - Early anatomists of the Adelaide Medical School. PMID- 3326569 TI - Organ transplantation--the state of play. PMID- 3326570 TI - Acute appendicitis in childhood: a feasibility study of computer-assisted diagnosis. AB - The case records of 169 children admitted to hospital with suspected appendicitis were subjected to Bayesian analysis in order to determine whether computer assisted diagnosis would be likely to reduce the negative laparotomy rate. The results suggest that the negative laparotomy rate could be reduced from 27% to 18% if computer-assisted diagnosis was used. PMID- 3326571 TI - Management of ascending aortic dissection: experience with the USCI intraluminal prosthesis and a method of aortic valve repair. AB - Ten consecutive cases of acute ascending aortic dissection operated on using the USCI intraluminal prosthesis from 1983 to 1986 were reviewed. Diagnosis was achieved by conventional angiography in six cases, by intraarterial digital subtraction angiography in one case, by computerized tomography (CT) scan in two cases and by echocardiography and abdominal ultrasound in one case. An entry site was seen in only five out of six conventional angiograms. At operation six of the 10 had a degree of tamponade. Aortic regurgitation was seen five times, due to dissection in four cases and to Marfan's disease in one. The entry site was controlled in eight cases. Repair using intraluminal prosthesis only was achieved in five cases. Aortic valve repair was added in four out of 10 cases, and in one of these an aorta-to-right coronary graft was also added. One case required aortic valve replacement. A method of aortic valve repair is presented. There were nine survivors, 1-36 months postoperatively. Of these, eight were asymptomatic on no medication. One had severe aortic regurgitation noted 2 months postoperatively and has mildly reduced exercise tolerance. Surgical treatment can be planned if the presence of dissection is proven and involvement of the ascending aorta is demonstrated. Early surgery is important, since six of the 10 cases in this series had tamponade. The intraluminal graft will reliably redirect flow to the true lumen and exclude the dissection from the pericardium. Aortic valve repair can be successful though late replacement may be necessary in some cases. Control of the entry site is not essential to achieve a good clinical result. PMID- 3326572 TI - The consequences of child sexual abuse: a review of recent research. PMID- 3326573 TI - Is asthma really changing? PMID- 3326574 TI - Comparison of a positive expiratory pressure (PEP) mask with postural drainage in patients with cystic fibrosis. AB - The use of a positive expiratory pressure (PEP) mask was compared with postural drainage in the treatment of 10 patients with cystic fibrosis. The patients were allocated randomly in a crossover fashion to the two regimens and evaluated initially by a physiotherapist and over a 4 week treatment period by use of a diary card. There was no significant difference in sputum production or change in lung function between each technique as assessed by the physiotherapist. Diary card evaluation also failed to demonstrate a difference in sputum production, symptom score or peak expiratory flow rate between the 4 week treatment periods. It was concluded that PEP mask therapy is an acceptable and effective alternative to postural drainage in interval therapy of patients with cystic fibrosis, although the patients have tended to revert to postural drainage during acute exacerbations. PMID- 3326575 TI - Parenteral absorption of insulin from the lung in diabetic children. AB - Semi-synthetic human insulin was delivered via a novel nebulizer to the respiratory tracts of six diabetic children. Blood glucose control obtained was at least as good as a control day when they received their usual dose of subcutaneous insulin. PMID- 3326576 TI - Spontaneous resolution of extrahepatic biliary obstruction in a neonate. AB - A patient with spontaneous resolution of complete extrahepatic biliary obstruction shortly after the neonatal period is described. Liver biopsy prior to resolution revealed widened portal tracts and extensive fibrosis; these changes normalized following resolution. The aetiology was not established but possibilities included a choledochal cyst, localized inflammation; for example, pancreatitis, a calculus of the common bile duct or a congenital membrane. Management of this patient would have been advanced if there were a paediatric size side-viewing duodenoscope which would have diagnostic and therapeutic potentials. PMID- 3326578 TI - Diversity in Hawaiian drosophilids: a tribute to Dr. Hampton L. Carson upon his retirement. International symposium. Honolulu, Hawaii, June 18-22, 1986. PMID- 3326579 TI - The dynamics of sexual selection and its pleiotropic effects. PMID- 3326577 TI - Adrenal haemorrhage presenting as an abdominal mass in the newborn. AB - Adrenal haemorrhage in the newborn, an entity well recognized at autopsy and as a cause of massive haemorrhage, may present as an asymptomatic abdominal mass. Three cases of neonatal adrenal haemorrhage are described and the literature is reviewed. Most of the affected babies were of normal birthweight, full term and with no history of difficult delivery or neonatal asphyxia. Most presented with a flank mass and jaundice. The haemoglobin was not always low. Intravenous urography and sonography were the investigations of choice. The most serious condition in the differential diagnosis is neuroblastoma, but the chance of this presenting in the newborn period with normal catecholamine secretion and no evident metastases is sufficiently rare to justify expectant management. Follow up physical examination and repeat sonography at 1 month are recommended. This interval is long enough to allow resolution of a mass caused by adrenal haemorrhage. PMID- 3326580 TI - Significance of anti-HTLV-III testing of volunteer blood donors. PMID- 3326581 TI - [The Tubingen concept of transfusion medical care in bone marrow transplants]. PMID- 3326582 TI - [Supportive therapy with thrombocyte concentrates in bone marrow transplant patients]. PMID- 3326583 TI - [HIV antibodies: test methods in the group trial]. PMID- 3326584 TI - [Cytapheresis for autoadoptive immunotherapy of tumors]. PMID- 3326585 TI - [Activation of peripheral blood granulocytes and monocytes by lymphokines in vitro]. PMID- 3326587 TI - [Results and current status of bone marrow transplantation with unrelated donors]. PMID- 3326586 TI - [Immunoenzyme demonstration of human interleukin-2 denaturation and renaturation]. PMID- 3326588 TI - [Experiences in the search for a histocompatible bone marrow donor in the family and in an unrelated population]. PMID- 3326589 TI - [ABO incompatibility in allogeneic bone marrow transplantation]. PMID- 3326590 TI - [A simple and cell-sparing method for obtaining stem cells slightly contaminated by erythrocytes in bone marrow transplantation with major ABO incompatibility]. PMID- 3326591 TI - [Importance of class-III and GLO alleles in the selection of HLA-identical bone marrow donors]. PMID- 3326592 TI - [Therapy of severe aplastic anemia (SAA) by bone marrow transplantation (BMT) or immunosuppression?]. PMID- 3326593 TI - [Changes in MHC expression after orthoptic liver transplantation]. PMID- 3326594 TI - [Induction of class-I MHC antigens on myocytes after heart transplantation: the pathomechanisms of the rejection reaction]. PMID- 3326595 TI - [A sensitive competitive enzyme immunoassay (CELIA) for the simultaneous measurement of platelet-associated immunoglobulins (IgG, IgM, IgA) and complement (C3c, C3d)]. PMID- 3326596 TI - [Demonstration of autoantibodies against extractable nuclear antigens(ENA) in immunoenzyme assay (ELISA) and in transmigratory electrophoresis]. PMID- 3326597 TI - [Safety of immunoglobulins in view of the transmission of LAV/HTLV-III]. PMID- 3326598 TI - [Transfusion-induced malaria tropica]. PMID- 3326599 TI - [Autologous autotransfusion]. PMID- 3326600 TI - [Importance of the HLA system for blood transfusion]. PMID- 3326601 TI - [Unusual migration of a Kirschner wire following drill wire fixation of a subcapital humerus fracture]. PMID- 3326602 TI - An ultraviolet light sensitive target in nitrate reductase of Escherichia coli K 12. AB - Ultraviolet light was shown to inactivate purified nitrate reductase in the presence of reduced benzyl viologen. Loss of activity was not complete, reaching 60 to 70%. Photolysis was maximum at 345 nm. The differential spectrum between native and irradiated enzyme exhibited absorption bands at 216, 275, 314 and 365 nm. The photosensitive electron carrier could be extracted by organic solvents. It had the following absorption bands: 225, 275 and 285 nm. It was reduced by Nile blue A but not by methylene blue. The precise nature of this light sensitive molecule could not be determined although the results support the idea that this chromophore might be a naphthoquinone. PMID- 3326603 TI - The antioxidative properties of carnosine, a natural histidine containing dipeptide. AB - The experimental results suggest that the antioxidative function of carnosine is one of the most important manifestations of its biological role. The ability of carnosine to interact directly with lipid peroxidation products was demonstrated. The effects of carnosine on partial restoration of lens transparency in dog eyes with senile cataract which is known to be caused by lipid peroxidation were demonstrated "in vitro" and "in vivo". PMID- 3326604 TI - Mutagenicity studies on thymomodulin. AB - Thymomodulin (Leucotrofina), an orally administrable thymic derivative endowed with interesting immunomodulating and myelomodulating properties, was tested for mutagenicity by means of the following in vitro and in vivo tests: mutagenesis on S. typhimurium with and without metabolic activation system (S-9), gene conversion on S. cerevisiae D 7 with and without metabolic activation, urinary assay in the mouse with and without metabolic activation, urinary assay in the mouse with S. cerevisiae D 7, host mediated assay in the mouse with S. cerevisiae and DNA repair test with and without metabolic activation. On the basis of the results obtained thymomodulin proved to be free of mutagenic activity. PMID- 3326606 TI - [Interactions of retroviruses and oncogenes with a cellular genomes. 2]. PMID- 3326605 TI - Comparison of antitumor properties of nitracrine and amsacrine analogs. AB - For seven new methoxy and/or nitro derivatives of acridine antitumor drugs, nitracrine and amsacrine, biological activity in a few in vitro tests, as well as activity against experimental murine tumors Sarcoma-180 and Leukemia L1210 were investigated. Acute toxicity on mice (LD50) was also determined. High activity in vitro and specific activity against Sa-180 were found to be characteristic features of nitracrine, whereas amsacrine was characterized by high antileukemic activity. Methoxylation of position 2 of the acridine ring in both drugs suppressed their characteristic activity. Besides, substitution of the aminoalkyl side chain in nitracrine by methanesulfon-m-anisidine group suppressed its high antitumor activity, and the presence of a nitro group in position 1 of amsacrine suppressed its antileukemic activity. Comparison of biological properties of nitracrine, amsacrine and their analogs indicated differences in some steps of their mode of action. PMID- 3326607 TI - [Pulmonary abscess: current concepts and treatment]. PMID- 3326608 TI - Nutritional problems in the elderly. PMID- 3326609 TI - Open-chest cardiac massage for non-traumatic cardiac arrest. PMID- 3326610 TI - The role of the suprachiasmatic nuclei in the regulation of circadian rhythms in mammals. PMID- 3326611 TI - [Integrative regulation of lactation]. PMID- 3326612 TI - Controlled-release therapeutic systems: technology applicable to the treatment of oral disease. PMID- 3326613 TI - Replacement therapy of the prevention of dental disease. PMID- 3326614 TI - Factor limiting dental diagnosis: a conceptual overview. PMID- 3326615 TI - Sonic diagnosis of skeletal defects: a preliminary study. PMID- 3326616 TI - The caries lesion under the scanning acoustic microscope. PMID- 3326617 TI - The elastic properties of a human mandible. PMID- 3326618 TI - Diagnostic imaging: finding the critical features. PMID- 3326619 TI - Computer-based reconstruction and temporal subtraction of radiographs. PMID- 3326620 TI - Dental holography--earlier investigations and prospective possibilities. PMID- 3326621 TI - NMR imaging in dentistry: relaxation and diffusion studies. PMID- 3326622 TI - The use of DNA probes in dental diagnosis and therapy. PMID- 3326623 TI - Resistance and susceptibility of mice to Leishmania major: a view from Melbourne. PMID- 3326624 TI - Analysis of host-protective and disease-promoting T cells. PMID- 3326625 TI - Anti-infectious responses in Leishmania major-infected BALB/c mice injected with recombinant granulocyte-macrophage colony-stimulating factor. PMID- 3326627 TI - ["Other intoxicating drugs" in traffic law]. PMID- 3326626 TI - Effects of relaxation training on recovery from myocardial infarction. PMID- 3326628 TI - [Phenotypic and genotypic properties of 4 virulence plasmids of Salmonella typhimurium]. AB - Virulence-associated plasmids pLT2, pIP1350, pIP1360 and pIP1370 coded for the fi+ character. These plasmids did not code for the synthesis of classical adhesins, aerobactin or colicins. Nor did they mediate resistance to the metals Hg, Te, As, Cd or flavomycin. Plasmids pLT2, pIP1350 and pIP1370 contained DNA sequences homologous to the incFIIA and incFIB replicons. Plasmid pIP1360 contained a single sequence homologous to incFIIA replicon. PMID- 3326629 TI - Effects of temperature inactivation of penicillin-binding protein 2 on envelope growth in Escherichia coli. AB - The transition from rod-shaped to spheroidal cells was studied in a temperature sensitive strain (SP45) of Escherichia coli K12, carrying a mutation (pbpA) in the gene coding for penicillin-binding protein 2 (PBP-2). This transition imposed by the restrictive temperature was associated with reduction of peptidoglycan/surface area and of cellular osmotic stability. Addition of nalidixic acid (20 micrograms/ml) at the temperature shift from 30 to 42 degrees C resulted in lysis of some cells and appearance of spheroidal bulges along the cylinders in other cells, consistent with the hypothesis of envelope weakening due to inactivation of PBP-2. PMID- 3326631 TI - Hypertension in pregnancy: whom and how to treat. AB - 1. Elucidation of some of the mechanisms responsible for blood pressure elevation in pregnancy has permitted therapy to be based on more rational principles. The decreased arterial reactivity encountered in normotensive pregnancy is most likely mediated by prostaglandins; preventive therapy using low dose aspirin is an option to prevent development of proteinuria in pre-existing hypertension and provide prophylaxis against pregnancy-induced hypertension. 2. Antihypertensive therapy utilizing sympathetic inhibition with either methyldopa or alpha- and beta-adrenoceptor blockade yields the most promising results. Vasodilation with hydralazine, calcium entry blockers (nifedipine), intravenous labetalol or diazoxide is primarily used in severely hypertensive patients. The use of orally administered nifedipine in severely hypertensive women is associated with encouraging results. 3. It is clear that women with blood pressure levels greater than 170/110 mm Hg need antihypertensive therapy for maternal safety; it remains to be proven to what extent foetal growth and welfare can be improved in women with diastolic pressure levels 85-110 mm Hg when adrenoceptor blocking agents are used for blood pressure control. Initial studies are suggestive of improved foetal growth, prevention of proteinuria and the respiratory distress syndrome but more long-term controlled studies are required. 4. In a recent study, at our institution, of foetal growth during long term antihypertensive therapy, treatment with pindolol yielded better foetal growth than therapy with atenolol. It is as yet unclear whether the ISA or beta 2-mediated vasodilation associated with pindolol was responsible for the improved foetal growth. Further controlled studies are indicated in hypertension in pregnancy to confirm the suggested benefits of beta-adrenoceptor blocker therapy. PMID- 3326630 TI - Attempts to establish phage typing as an epidemiological marker for Salmonella enteritidis. AB - The notable increase in the number of Salmonella enteritidis strains seen in Spain in recent years (from 27.10% in 1980 to 66.36% in 1985) makes it necessary to find an additional epidemiological marker for this serotype. Phage typing was considered because of its discriminatory capacity toward other Salmonella serotypes. Wild and lysogenic bacteriophages were sought for a set of autochthonous bacteriophages. Our set consisted of 6 bacteriophages, 5 wild and 1 lysogenic. When tested on 1,500 selected strains, they produced 9 different phage types. The most abundant phage types were A (74.66%) and B (19.73%). The percentage of non-typable strains was low: only 1.4% from a total of 1,500 strains failed to produce lysis with our set. This reflects the high typability of the bacteriophage set proposed. PMID- 3326632 TI - The large studies in hypertension: what have they shown? PMID- 3326633 TI - ISA--vasodilatation: improvement of organ perfusion. AB - 1. In almost all forms of established hypertension the increase in blood pressure can be attributed to increased total peripheral vascular resistance. 2. beta adrenoceptor blocking compounds, which are frequently used as first-line therapy in hypertension, may compromise blood flow to vital organs in view of the fact that they reduce cardiac output both acutely and during long-term treatment. 3. beta-adrenoceptor blocking agents with a marked intrinsic sympathomimetic activity (ISA) such as pindolol differ in this respect by lowering arterial pressure without lowering cardiac output while causing a reduction in total peripheral resistance. 4. Direct vascular effects of beta-adrenoceptor blockers with marked ISA could contribute to the normalisation of hypertension-induced structural arteriolar changes. The effect appears to be dissociated from the effect caused by the lowering of blood pressure per se. PMID- 3326635 TI - Reversibility of structural changes in the resistance vessels in hypertension: a review of studies with pindolol. AB - 1. In recent years evidence has accumulated which indicates that although various beta-adrenoceptor antagonists are equally effective in lowering blood pressure in patients with essential hypertension the mechanisms of action of the different drugs are heterogeneous. 2. Pindolol, a beta-adrenoceptor antagonist with pronounced intrinsic sympathomimetic activity (ISA) appears, to some extent, to act via peripheral vascular mechanisms. 3. Following prolonged treatment with pindolol in essential hypertension peripheral vascular resistance at maximal vasodilatation has been found to be decreased compared with the pretreatment values suggesting that the structural vascular changes characteristic of established hypertension may be reversible. PMID- 3326634 TI - Comparison of the onset of the antihypertensive action of pindolol and propranolol. A 24 h haemodynamic study. AB - 1. Haemodynamic changes during the onset of the antihypertensive action of pindolol, 10 mg twice daily, and propranolol, 80 mg three times daily, were studied for 24 h in two groups of 10 patients with uncomplicated essential hypertension. 2. Baseline haemodynamics were not different between the two groups. 3. Pindolol, with considerable intrinsic sympathomimetic activity (ISA) exerted its maximal antihypertensive efficacy within 3-4 after dosing (-15 +/- 3%, mean +/- s.e. mean, P less than 0.001). This effect was maintained for 24 h. 4. After propranolol, which is devoid of ISA, arterial pressure fell more gradually, but after 24 h the two drugs shared an equal antihypertensive effect. 5. Cardiac output rose after pindolol by 16 +/- 5% (P less than 0.01). It decreased transiently by 16 +/- 6% (P less than 0.01) 1-4 h after propranolol. At that time vascular resistance had risen by 18 +/- 5% (P less than 0.001). 6. The onset of the antihypertensive action of the two drugs was associated with reductions in vascular resistance. Since reflex vasoconstriction did not occur after pindolol, vascular resistance was always lower on this drug than on propranolol (-29 +/- 4%, P less than 0.001 vs -15 +/- 5%, P less than 0.01). 7. Cardiac filling pressures, pulmonary artery pressure and pulmonary vascular resistance did not change after pindolol but they rose after propranolol. 8. During the onset of the vasodilator and antihypertensive effects of the two beta adrenoceptor blockers heart rate, stroke volume and cardiac output rose, despite cardiac beta-adrenoceptor blockade, suggesting a reduction of parasympathetic tone and an increase in venous return.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3326636 TI - Comparison of the effect of pindolol vs propranolol on the lipid profile in patients treated for hypertension. PMID- 3326637 TI - The living cell as an energy-transducing machine. A minimal model of myocardial metabolism. PMID- 3326638 TI - [Isolation and characteristics of surface proteins from Streptococcus group A]. AB - Cell wall surface proteins of group A Streptococcus type 29 were extracted with 1 M hydroxylamine pH 6.0. The purification procedure included fractionation with ammonium sulfate and gel filtration on Sephadex G-150. SDS polyacrylamide gel electrophoresis revealed a number of proteins (approximately 20) with molecular mass of 70 kD; the difference in Mr between the proteins was 5-10 kD. Isoelectrofocusing demonstrated that the proteins are either acid (pI = 3.7) or weakly alkaline (pI = 7.7). Possible reasons for the heterogeneity of Streptococcus cell wall surface proteins are discussed. PMID- 3326639 TI - [Biochemical characteristics of new thermosensitive secretory mutants of yeasts]. AB - New thermosensitive mutants of the yeast Saccharomyces cerevisiae which block the secretion of periplasmic enzymes at restriction temperature have been obtained. These mutants accumulate active low molecular weight and mature invertase species in the cell; the buoyant density of the cells in a Percoll gradient is higher than that in the wild strain cells. The mutant cells transferred to permissive temperature (25 degrees C) in the absence of protein synthesis can secrete some amount of accumulated invertase. It was found that the secretory defects of conditional mutants do not affect the activity of cytoplasmic enzymes (e.g., alcohol dehydrogenase) or the level of total protein synthesis and glycosylation and do not induce non-specific disturbances in energy metabolism and plasma membrane functions at restriction temperature. Some strains of new secretory mutants revealed uncoupled defective secretion of periplasmic enzymes and intrinsic membrane proteins (proline permease). The possibility of branching of the secretory pathway for periplasmic enzymes and cytoplasmic membrane proteins is discussed. PMID- 3326640 TI - [Constructive ecological approach to the problems of protecting the biosphere]. PMID- 3326641 TI - Artificial intelligence and artificial organs. PMID- 3326642 TI - [Academic eulogy of Prof. van den Branden, titular member and former president]. PMID- 3326644 TI - Seronegative spondylarthropathies. PMID- 3326643 TI - Chagas' cardiopathy and Trypanosoma cruzi zymodemes in Chile. PMID- 3326645 TI - [Removal and exchange of intraocular lenses]. PMID- 3326646 TI - Sequential appearance of cytoskeletal components during the early stages of neurite outgrowth from cerebellar granule cells in vitro. AB - Cerebellar granule cells derived from one-week-old rat pups have been placed into culture to examine the expression of microfilament, microtubular and neurofilament proteins in developing neurites up to 2 days in vitro. Immunofluorescence and rhodamine-phalloidin studies have shown that the first cytoskeletal element to appear in the developing neurite was the microfilament network which was present in cell processes and expansions from at least 8 minutes in vitro. Rhodamine-phalloidin fluorescence was maintained in the developing neurite over 2 days and was enriched in some growth cones. At between 30 and 60 min in culture microtubules (reacting with anti alpha-tubulin antibodies) appeared in the neurites but did not ramify throughout the growth cone at this or later time points. The expression of tyrosylated alpha-tubulin in microtubules of the developing neurite appeared to precede that of acetylated alpha-tubulin. Only one of the neurofilament subunits, the 200 kDa subunit, could be positively identified in granule cell processes in these cultures. The developmental pattern of cytoskeletal protein expression in granule cell neurites in vitro may reflect a process of stabilisation of the growing neurite behind an active, motile growth cone. PMID- 3326647 TI - Paraventricular neurons control hamster photoperiodism by a predominantly uncrossed descending pathway. AB - Exposure of Syrian hamsters (Mesocricetus auratus) to short daylengths triggers testicular regression through a pathway involving hypothalamic regulation of sympathetic control over melatonin production in the pineal gland. Destruction of the hypothalamic paraventricular nucleus (PVN) blocks this response. In order to determine whether descending paraventricular influences are crossed or uncrossed, we removed the superior cervical ganglion unilaterally and destroyed the PVN on the same or opposite side. Ipsilateral PVN lesions were consistent with gonadal regression and high nocturnal pineal melatonin levels, while contralateral lesions blocked regression and significantly reduced the melatonin content of the gland. In order to determine whether PVN cell bodies are critical to the photoperiodic response, we produced axon-sparing lesions by injection of ibotenic acid. Lesions which produced cell loss as verified by both Nissl staining and immunocytochemistry blocked gonadal regression in hamsters exposed to short days. These findings indicate that PVN cells regulate pineal function, and hence gonadal regression, by a predominantly uncrossed pathway. PMID- 3326648 TI - Immunological detection of high molecular weight proteins by gel and blot overlay. AB - The sensitivity and specificity of the gel overlay and western blot methods of immunodetection are compared for spectrins, typical high molecular weight proteins. The gel overlay method is more sensitive and specific for the immunodetection of brain spectrin (240/235) and rbc spectrin. As the western blot technique will remain the method of choice for many applications because of its relative speed, we discuss methods for optimizing its sensitivity and selectivity. PMID- 3326649 TI - Immunocytochemical distribution of [Met]enkephalin-Arg-Gly-Leu immunoreactivity in the rat diencephalon. AB - Recently, [Met]Enkephalin-Arg-Gly-Leu (MEAGL) was isolated from bovine adrenal glands, and it was found to be derived exclusively from proenkephalin. Therefore, we investigated the distribution of MEAGL-like immunoreactive neuronal perikarya and fibers in the rat diencephalon pretreated with colchicine by PAP immunocytochemistry. In the thalamus MEAGL immunoreactive neuronal perikarya were distributed in the paraventricular nucleus and the ventral part of the lateral geniculate nucleus. Immunoreactive fibers were found in the paraventricular, paracentral, anteroventral, reuniens and rhomboid nuclei. In addition, immunoreactive fibers were also noted in the anterior pretectal nucleus. In the hypothalamus, immunoreactive neuronal perikarya were observed in the medial preoptic area, anterior and lateral hypothalamic nuclei, perifornical region, parvocellular and postero-magnocellular regions of paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus, arcuate nucleus, premammillary, medial mammillary and lateral mammillary nuclei. The distribution of immunoreactive fibers was similar to that of neuronal perikarya. However, immunoreactive fibers were also observed in the supraoptic and suprachiasmatic nuclei where no immunoreactive neuronal perikarya were detected. Numerous immunoreactive fibers were detected in the external layer of the median eminence, but there were few in the internal layer. The similarity and difference in the distribution between MEAGL and other proenkephalin peptides such as [Met]enkephalin were also discussed. PMID- 3326650 TI - [Increasing insulin binding and degradation in isolated human erythrocytes with n heptane and n-hexane and the effect of trypsin and dithiothreitol]. PMID- 3326651 TI - Acute monocytic leukemia in children. Response to VP-16-213 as a single agent. AB - Three patients were studied: two infants with acute monocytic leukemia who failed to respond to the initial combination therapy of daunorubicin with cytosine arabinoside, and an adolescent with relapsed acute monocytic leukemia. They were intensively treated with epipodophyllotoxin (VP-16-213) alone and subsequently had complete remission. One patient showed apparently dose-dependent cytotoxic effect. All three patients have maintained complete remission for 6, 7, and 11 months, respectively. Toxicities, including myelosuppression, alopecia, nausea, vomiting, and renal dysfunction, were well tolerated. Intensive treatment with VP 16-213 alone was thus found to have a potent therapeutic effect on acute monocytic leukemia in children. VP-16-213 deserves a further assessment in the therapeutic protocol for patients with childhood acute monocytic leukemia. PMID- 3326652 TI - Poorly differentiated, neuron-specific enolase positive round cell tumor with two translocations t(11;22) and t(21;22). AB - The authors describe a highly malignant, disseminated round cell tumor originating in the ninth rib of a 14-year-old boy. Extensive studies by means of light and electron microscopic examination, histocytochemistry and immunocytochemistry and cytogenetic analysis revealed an undifferentiated, neuron specific enolase positive round cell tumor with a unique karyotype: 45,XY, 21,t(11;22)(q23;q11), der(22)t(21;22)(q11.2;p11). Thus, despite the absence of definite morphologic features, such as Homer-Wright rosettes, neurosecretory granules and cytoplasmatic processes, these findings suggest a neuroectodermal origin of this bone tumor. PMID- 3326653 TI - Cancer of the pancreas. 50 years of surgery. AB - The course of 196 patients with proven carcinoma of the pancreas seen at Yale New Haven Hospital from 1972 to 1982 was analyzed. Only 73% of the patients were preoperatively expected to have cancer of the pancreas. The patients who underwent resection had the longest mean survival but also the longest total hospital stay. Twenty-seven patients survived 1 year or more, but nonresected patients constituted 81.5% of this group. The only 5-year survivor did not undergo resection. Forty-seven percent of patients who survived 1 year and had not undergone gastroduodenal bypass, developed duodenal obstruction. It was not possible to identify a subset of patients with a favorable prognosis. A review totaling approximately 37000 patients, of whom 4100 had undergone resections, revealed only 156 survivors, 12 of whom had not been resected, for an overall survival rate of only 0.4%. No author had more than 3.4% of the total number of patients as 5-year survivors. PMID- 3326654 TI - Primary osteosarcoma of the liver. AB - Extraskeletal osteosarcomas are infrequent, and those that arise within parenchymal organs are very rare indeed. This case of a 71-year-old man with a primary osteosarcoma of the liver is the second reported in man. Pathologic findings, including ultrastructural features, at surgery and autopsy are presented. The differential diagnosis is discussed in detail. PMID- 3326655 TI - Stress and cancer. AB - Stress is a term that has been variously defined in the literature. In the context of research into psychophysiological aspects of cancer, 'stress' usually refers to stressful events occurring in people's lives, such as bereavement or unemployment. The effects of stress in terms of psychological morbidity and physical illness are being studied more and more. Experimental work has been conducted using animals but the results are contradictory and inconclusive. It is postulated that the effects of stress are mediated hormonally or immunologically, and there is evidence in support of this view from both animal experiments and human studies. Other mechanisms may also exist. Observations that stress is implicated in the onset of cancer have been traced back to the sixteenth and seventeenth centuries. Early studies were methodologically flawed, however, and results from recent, more carefully controlled investigations have not supported consistently the connection between stress and cancer. The methodological problems to be overcome in this area are still enormous, not least that of causality: because the data of onset of malignancy is uncertain, it is impossible to know whether a stressful event preceded or followed the genesis of cancer. Recurrence of cancer is easier to date and more amenable to study. The contributory role of stress in recurrence or reactivation of tumour growth may be a more fruitful line of inquiry. Different methods for measuring stress are available. Questionnaires which patients complete themselves have been criticized on the grounds that they ignore the meaning and context of stressful events, and because their scoring systems imply additivity. Interview methods are superior and reliable, although more costly and time consuming. Studies that seek to measure the effects of stress on the course of cancer should control for intervening variables such as personality and social support. PMID- 3326656 TI - The psychiatrist's role in cancer care. PMID- 3326658 TI - Psychological and social consequences of cancer. PMID- 3326657 TI - Mental adjustment to cancer: its measurement and prognostic importance. AB - Can the mental adjustment of patients to cancer influence the course of their disease? This question is considered in a critical review of relevant studies. Salient problems in this field of research are identified and basic methodological requirements outlined. The few systematic, prospective investigations which meet these requirements show evidence for an association between mental adjustment to cancer and subsequent outcome in patients with 'early'--ie non-metastatic disease. The evidence, however, should be regarded as provisional rather than conclusive. A definitive answer will require further carefully controlled long-term follow-up studies. In such studies, a crucial methodological issue is the measurement of mental adjustment to cancer. Hitherto, this has been based solely on clinical assessments. The development of a new measure of mental adjustment to cancer is reported. The MAC scale is a 40-item self-rating questionnaire. Initial results based on a study of 235 patients with a variety of cancers indicate that the scale is acceptable to patients, easy to administer in busy oncology clinics, reliable and stable over time. Its validity as measured by spouses' ratings appears satisfactory. Further evaluation is required. These preliminary results suggest that the MAC scale is a suitable, easily replicable method of measuring adjustment to cancer in studies of large numbers of patients. PMID- 3326659 TI - Psychiatric aspects of cancer in the aged. AB - The greatest risk factor for cancer is ageing, yet little is known about the epidemiology and treatment of psychiatric disorders in the aged cancer population. This is particularly true for the group over 75 years of age. Four important areas of psychiatric treatment relevant to the aged cancer patient are: illness behaviour, cognitive disorders, depression and psychosocial adaptation. Within these areas the following four conclusions can be made: (a) Symptom presentation and health promoting practices are two important aspects of illness behaviour that affect the detection and prevention of cancer in the aged. (b) It is likely that there will be an increased co-occurrence of dementia and cancer, raising important issues of treatment and informed consent. (c) There appears to be evidence that depression in cancer patients does not increase with age. (d) Similar to depression, despite widely differing methods and age cutoffs, the results of several studies have shown that psychosocial adaptation to cancer is maintained with age. With respect to psychiatric treatment, no patient should be denied full use of appropriate therapy on grounds of old age alone, and more attention should be given to the systematic detection and evaluation of reversible cognitive disorders. PMID- 3326660 TI - Measurement of quality of life in patients with cancer. PMID- 3326661 TI - Personality, coping style, emotion and cancer: towards an integrative model. AB - What this paper attempts, which may be different than previous reviews of the literature regarding the role of certain psychosocial factors and cancer initiation/progression, is to propose a model wherein seemingly discrepant findings may be integrated and understood. For this task, a representative but not an exhaustive review of studies was conducted, which revealed surprising consistencies, given the heterogeneity of designs, measures and cancer sites. Evidence converges on a constellation of factors that appears to predispose some individuals to develop cancer more readily or to progress more quickly through its stages. These factors include (a) certain personality traits or coping styles, which were discussed under the rubric of 'Type C'; (b) difficulty in expressing emotions; and (c) an attitude or tendency toward helplessness/hopelessness. Next, illustrative discrepancies across studies were presented. In order to make sense of these seemingly discrepant results, a process model of coping style and psychological-physiological homoeostasis was proposed. This model may be used to understand why some studies have found that Type C is associated with cancer outcome measures, while others have found that helplessness/hopelessness or emotional expression is related to outcome. We would expect that these differences are attributable to the point in the cancer and coping process at which psychological assessment was conducted. PMID- 3326662 TI - Improving the therapeutic index of systemic therapy with special emphasis on cisplatin and carboplatin. PMID- 3326664 TI - Bone marrow transplantation. PMID- 3326663 TI - In vitro screening of new drugs and analogues--specificity and selectivity. AB - The use of human tumors for in vitro evaluation of new drugs and analogues is currently receiving widespread attention. Results from initial preclinical studies have definitely provided the impetus for continuing such investigations, refining the methodologies and establishing larger series of cell lines from biopsies so as to increase the validity of attempts to define tumour types most responsive to active new agents or specific drug combinations. PMID- 3326665 TI - Improvement of therapeutic index in gastrointestinal cancer. PMID- 3326666 TI - Treatment toxicity reduction: breast cancer. AB - Since curative treatment of advanced breast cancer is still beyond our reach, the importance of reducing overall toxicity of systemic treatment must be stressed. This seems to be possible by adapting the form and intensity of therapy to the prognosis and stage of disease and by using drugs exhibiting high antitumoral efficacy combined with low systemic toxicity. In 475 patients with metastatic breast cancer, we initiated a prognosis-oriented therapeutic strategy. We developed a prognostic score so as to classify patients into 'high' and 'low' risk groups. In this way we were able to separate patients into two groups with statistically different survival times. In addition, we found that the impact of the first polychemotherapy on survival is different when comparing patient with favourable and unfavourable prognostic scores. Patients with favourable prognostic factors had exactly the same survival time independent of tumour progression, stable disease or even partial remission. Only patients achieving a complete remission survived longer. In contrast, patients with unfavourable prognostic factors apparently benefited from chemotherapy. Patients achieving stable disease or objective tumour remission had a significantly longer survival time than those patients with immediate tumour progression. Additionally, for most of the patients in this group, chemotherapy induced a transient stabilization or improvement of tumour induced symptoms. Therefore, we conclude that chemotherapy of advanced breast cancer is necessary. However, to reduce overall toxicity, it must be planned and administered according to the prognostic picture of the individual patient. PMID- 3326667 TI - Mitoxantrone: an active, new antitumor agent with an improved therapeutic index. PMID- 3326668 TI - Daunomycin- and adriamycin-N-(2-hydroxypropyl)methacrylamide copolymer conjugates; toxicity reduction by improved drug-delivery. PMID- 3326669 TI - Biologic considerations for drug targeting in cancer patients. AB - There is a great need for more specific targeting of chemotherapeutic agents, but development of specific therapy will be difficult in light of the barriers which separate a tumor from the vasculature, tumor cell heterogeneity and instability, technological advances necessary for drug delivery design and introduction into the clinic and mechanisms for assessment of efficacy (Table 5). While imposing, these problems are not insurmountable. A clearer understanding of the specific goal of a drug delivery/drug targeting approach will make the expectations more realistic and the chances for success greater. Primary to improving drug targeting is a better understanding of the biology of tumors. There are a number of limitations to drug targeting technology mentioned above, but, at present, the more difficult limitations are imposed by tumors themselves and the host's response to a tumor. Currently available technology does not offer Erlich's magic bullet and it does not appear that a single entity will suffice for cancer. Perhaps a mixture of drug delivery systems, each reducing the toxicity of a particular component of therapy will provide the first realistic goal in drug targeting. Each form of drug targeting is limited by biochemical and biophysical properties of the host, tumor cells, drug delivery system and interactions between them. Successes in vitro are moot without corresponding data in the (unfortunately) more complex organismic level. Development of drug targeting approaches will also require a critical, thorough evaluation of the ability to specifically deliver drug in vivo. PMID- 3326670 TI - Some procedures to reduce cis-platinum toxicity reduce antitumour activity. PMID- 3326671 TI - The use of maxillary centrals and laterals in the overdenture patient. PMID- 3326672 TI - Microleakage of type C preventive resin restorations. PMID- 3326673 TI - Osseous grafting in periodontal therapy, Part II: Nonosseous graft materials. PMID- 3326674 TI - An overview of the use of posterior composites in clinical practice. PMID- 3326675 TI - Splenic blood flow measurements by Doppler ultrasound: a preliminary report. AB - Splenic blood flow and splenic volume were measured by Doppler and cross sectional ultrasound in 72 human subjects consisting of 61 patients with splenomegaly and 11 normal subjects. This non-invasive and relatively simple method yielded satisfactory results in 76% of the subjects studied; failures were due to obesity, debility, distorted vascular anatomy, and excessive gas in the stomach. These preliminary results suggest that the Doppler ultrasound technique is a practical clinical method for measuring splenic blood flow. PMID- 3326676 TI - Double-blind comparison of meclofenamate sodium with codeine and placebo for the pain of episiotomy. AB - Meclofenamate sodium, a nonsteroidal anti-inflammatory agent, was compared at two dose levels (100 mg and 200 mg) with codeine (60 mg) and placebo in a double blind, randomized study of 218 women after normal vaginal delivery. The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain. Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity. The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain. Adverse experiences with the study medications were minimal (6.4%). Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium. Meclofenamate sodium is a safe, effective analgesic for acute episiotomy pain. PMID- 3326677 TI - Comparison of meclofenamate sodium with codeine and placebo for the treatment of episiotomy pain. AB - Meclofenamate sodium, a nonsteroidal anti-inflammatory drug with proven analgesic effects, was compared at two dose levels (200 mg and 100 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 327 women experiencing episiotomy pain after normal delivery. Meclofenamate sodium at either dose was significantly better than codeine or placebo in reducing pain intensity and increasing pain relief, and it had a longer duration of action. Adverse effects were minimal, and their frequency did not differ significantly among treatment groups. Meclofenamate sodium appears to be as safe as and more effective than codeine for the management of episiotomy pain. PMID- 3326678 TI - Comparison of meclofenamate sodium with buffered aspirin and placebo for the relief of postoperative dental pain. AB - The analgesic effect of meclofenamate sodium at two dose levels (100 mg and 200 mg) was compared with the effects of buffered aspirin (600 mg) and placebo in a double-blind, randomized study of 105 dental outpatients with acute pain following third-molar extraction. Meclofenamate sodium at either dose level was significantly superior to both buffered aspirin and placebo, resulting in significantly greater relief of pain. All four treatments were well tolerated, and side effects were minimal. Meclofenamate sodium is a safe, highly effective analgesic for the relief of acute pain. PMID- 3326679 TI - Comparative efficacy and safety of immediate-release and controlled-release hydralazine in black hypertensive patients. AB - Twenty-nine black hypertensive patients were randomized to treatment with controlled-release hydralazine capsules administered BID or QD, or immediate release hydralazine tablets administered TID, for at least four weeks in a double blind, parallel study. Hydralazine was begun after a two-week to four-week period in which blood pressure was not adequately controlled with diuretics alone. Each patient initially received 75 mg/day of the assigned drug. The dosage could be increased to 150 or 300 mg/day at weekly intervals if sitting diastolic blood pressure was not adequately controlled (greater than 90 mmHg). A beta-blocker (80 mg/day of nadolol) was added only for patients who had beta-blocker-responsive adverse effects that could not be controlled otherwise. Nine patients were considered unevaluable because of protocol violations or withdrawal from the study before completion of four weeks of treatment, primarily because of adverse effects. Twenty patients were included in the efficacy evaluation. Controlled release hydralazine BID produced statistically significant mean falls from baseline in sitting diastolic blood pressure and in standing systolic blood pressure and an almost significant drop in standing diastolic blood pressure. Although the other two treatment groups also had substantial falls in all blood pressure measurements, the changes from baseline were not statistically significant. No significant difference in response was noted between patients who received a beta-blocker and those who did not. There were no statistically significant differences among the three treatment groups in incidence and severity of adverse effects or electrocardiographic abnormalities. A statistically, but not clinically, significant fall in hemoglobin, hematocrit, and red blood cell count was observed in all three treatment groups. PMID- 3326680 TI - The existence of renin-angiotensinogen system in the rat fetal brain: I. Immunocytochemical localization of renin-like activity at the 19th day of gestation. PMID- 3326681 TI - The existence of renin-angiotensinogen system in the rat fetal brain: II. Immunocytochemical localization of angiotensinogen in the telencephalon and the diencephalon. PMID- 3326682 TI - Trypanosoma cruzi: cardiac myocells alterations due to spontaneous or therapeutically induced intracellular parasite disintegration. PMID- 3326684 TI - Pulmonary valvotomy. PMID- 3326685 TI - [Advances in research on respiratory tract diseases with reference to immune processes]. PMID- 3326686 TI - [Georges Fabiani (1908-1987)]. PMID- 3326683 TI - Regulatory properties of brain glutamate decarboxylase. AB - 1. Glutamate decarboxylase is a focal point for controlling gamma-aminobutyric acid (GABA) synthesis in brain. Several factors that appear to be important in the regulation of GABA synthesis have been identified by relating studies of purified glutamate decarboxylase to conditions in vivo. 2. The interaction of glutamate decarboxylase with its cofactor, pyridoxal 5'-phosphate, is a regulated process and appears to be one of the major means of controlling enzyme activity. The enzyme is present in brain predominantly as apoenzyme (inactive enzyme without bound cofactor). Studies with purified enzyme indicate that the relative amounts of apo- and holoenzyme are determined by the balance in a cycle that continuously interconverts the two. 3. The cycle that interconverts apo- and holoenzyme is part of the normal catalytic mechanism of the enzyme and is strongly affected by several probable regulatory compounds including pyridoxal 5' phosphate, ATP, inorganic phosphate, and the amino acids glutamate, GABA, and aspartate. ATP and the amino acids promote apoenzyme formation and pyridoxal 5' phosphate and inorganic phosphate promote holoenzyme formation. 4. Numerous studies indicate that brain contains multiple molecular forms of glutamate decarboxylase. Multiple forms that differ markedly in kinetic properties including their interactions with the cofactor have been isolated and characterized. The kinetic differences among the forms suggest that they play a significant role in the regulation of GABA synthesis. PMID- 3326687 TI - The histopathology of naturally-occurring cutaneous leishmaniasis in the reservoir host, Psammomys obesus. AB - Ears from infected Psammomys obesus, the gerbil reservoir host of Leishmania major, were histopathologically studied. The histopathology was a chronic localized infection consisting of an epithelioid granuloma with greatly increased populations of mast cells, melanocytes and melanophores; ulceration was present and parasites were always very few and inside parasitophorus vacuoles. PMID- 3326688 TI - [Apropos of the origin of some diseases raging in Madagascar]. AB - Madagascar had been separated from african continent since 5 millions years and, if flora and fauna are endemic (40 species of lemuriens) all of parasites and humans populations are imported, from africa with respect to P. falciparum, P. malariae, S. mansoni and S. haematobium (but snails are endemic ), Fasciola gigantica (imported with zebus) and perhaps P. vivax, and from Asia with respect to W. bancrofti, N. americanus, C. cellulosae (imported with pigs) and perhaps P. vivax, chromoblastomycosis is autochthonous and of high frequency. Malagasy were natives of Indonesia, Africa, Arabia and Europe. PMID- 3326689 TI - The effect of two new alpha-glucosidase inhibitors on metabolic responses to a mixed meal in normal volunteers. AB - 1. alpha-Glucosidase inhibitors delay carbohydrate absorption and have been proposed as adjunctive therapy for diabetes mellitus. 2. To determine the effects of two new alpha-glucosidase inhibitors, Bay-m-1099 and Bay-o-1248, on meal carbohydrate and lipid tolerance, plasma glucose, insulin and triglyceride levels were measured at 15-60 min intervals over 12 h after ingestion of a standard breakfast, lunch and dinner of identical composition in 31 normal volunteers. 3. The volunteers were randomized to receive either Bay-m-1099 (50 or 25 mg) or placebo prior to each meal, or the single administration of Bay-o-1248 (20 or 10 mg) or placebo prior to breakfast. 4. Only Bay-m-1099 at the 50 mg dose reduced significantly the postprandial increase in plasma insulin levels after each meal when compared with placebo (25, 36, 54% at breakfast, lunch, and dinner, respectively; P less than 0.05). Both drugs were well tolerated, with side effects limited to complaints of flatulence. 5. Thus, with the dosage schedule employed, Bay-m-1099, but not Bay-o-1248, significantly reduced postprandial increments in plasma insulin. PMID- 3326690 TI - The role of interleukin 1 in the pathogenesis of rheumatoid arthritis. PMID- 3326692 TI - The arthropathy of chronic haemodialysis. AB - The occurrence of rheumatic disorders in patients treated by long-term haemodialysis (HD) has been emphasized for several years. Complications include carpal tunnel syndrome and various arthropathies. Together with renal osteodystrophy, they are the main limiting factors for the quality of long-term survivals. The pathophysiology is still poorly understood but apatite crystal deposition, aluminum or iron overload and the articular deposition of a new type of amyloid may play a part. We will attempt here to review the available data on these rheumatic disorders in dialysis patients. PMID- 3326691 TI - Scleroderma: DR antigens, autoantibodies and clinical manifestations. AB - The relationship between anticentromere antibodies (ACA), antitopoisomerase I or Scleroderma 70 (Scl-70) antibodies, HLA-DR antigens, and clinical manifestations of scleroderma were examined in 51 patients defined by ARA criteria. No association between a given HLA-DR antigen and either ACA or anti-Scl-70 was found. Statistically significant associations were noted for patients with ACA who had a lower frequency of arthritis and longer disease duration; anti-Scl-70 patients were more likely to be males with a higher frequency of pulmonary, cardiac and sicca symptoms. PMID- 3326693 TI - Genetic control of susceptibility to atherosclerosis (with special emphasis on the role of the macrophage). AB - The pathogenesis of atherosclerosis involves a complex interplay of arterial endothelium, multiple cellular constituents, and circulating lipo/apolipoproteins. Early work implicated a single etiology--either excess of circulating lipids, disruption of endothelial integrity, or clonal proliferation of smooth muscle cells. However, current research supports a hypothesis unifying endothelial disruption with lipid imbibation. The macrophage is recognized as having an integral role in atherogenesis due to its capacity to adhere to endothelium, internalize and metabolize lipids, and liberate proteases, apolipoproteins, and mitogens. Genetically determined susceptibility or resistance to atherosclerosis has long been described in animals and man, and differences in lipo/apolipoproteins have been proposed to explain these variations. Genetically defined variants of inbred mice have been used to pursue hereditary influences in atherogenesis. Strain variations in lipid metabolism have been advanced as one possibility to explain a polygenic mode of inheritance- those strains most replete in cholesterol-enriched lipoproteins demonstrating the greatest susceptibility. However, there is now a substantial body of evidence suggesting that the diverse functions of the macrophage may be the mechanism underlying the genetic polymorphism in atherosclerosis. Recombinant inbred strains of mice may serve as a vehicle through which this concept can be explored. PMID- 3326694 TI - Hemodynamic and neurohumoral factors in the response of hypertensives to hydrochlorothiazide therapy. AB - We investigated the roles of the renin-angiotensin-aldosterone axis, the sympathetic nervous system, and the responses of the forearm vascular bed in the antihypertensive action of hydrochlorothiazide. Plasma renin activity, aldosterone, catecholamines, blood pressure, and forearm blood flow were measured before and after 8 weeks of hydrochlorothiazide therapy in 21 hypertensive patients whose blood pressures responded to the diuretic, and were then compared to a similar group of 19 hypertensives who did not respond to the thiazide therapy. Dietary salt intake was stable and comparable for the two groups. In the responsive patients, administration of the diuretic caused a significant fall in supine systolic and diastolic blood pressure and forearm vascular resistance, with constant forearm blood flow. No significant changes were noted in these parameters in the non-responsive group. Plasma renin activity and aldosterone concentration was increased in both groups to a comparable extent but plasma norepinephrine and epinephrine concentrations were increased to a greater extent (p less than 0.01) in the responsive group. Heart rate did not change significantly in either group in spite of significant increases in circulating epinephrine. The results are consistent with minimal thiazide-induced volume and salt depletion in either study group. The reduction in blood pressure and forearm vascular resistance observed in the responsive group appears to be the result of diminished target-organ sensitivity towards catecholamines and possibly angiotensin II. PMID- 3326695 TI - Mechanical properties of vascular smooth muscle in hypertension. AB - Reports from several laboratories indicate that the early part of smooth muscle contraction is achieved by normally cycling crossbridges, while the later part is subserved by slowly cycling or latch-bridges. We have recently found that the early bridges are responsible for almost 75% of the maximum shortening of the muscle. The latch bridges appear to be responsible for force production. The earliest change in the mechanical properties of caudal arteries from spontaneously hypertensive rats (SHR) is an increase in maximum shortening ability (delta Lmax), at a time when there is no detectable change in maximal isometric tetanic tension (Po). This substantiates the hypothesis that changes in Po are late indices of disease. The increased delta Lmax is associated with increased maximal velocity of shortening (Vo) of early cross-bridges, whereas latch bridge activity is normal. This provides the first subcellular explanation for the increase in delta Lmax. Since hypertension must result from narrowing of blood vessels, delta Lmax is, parenthetically, the important variable to study. Changes in Po, while contributing to increased vascular wall stiffness, do not directly account for the increased resistance. The cause of the increased cycling rate of crossbridges is probably increased myosin ATPase activity, or myosin light-chain phosphorylation by the specific kinase. Studies in helical sections of caudal, and segments of mesenteric resistance arteries provided similar results, confirming the suitability of caudal arteries as a model of resistance vascular units. The larger vessel is of course much easier to work with. PMID- 3326696 TI - Abnormalities in the regulation of sympathetic activity in human hypertension. AB - Various biochemical, pharmacologic, and physiologic techniques were used to evaluate the sympathetic tone and reactivity in labile and sustained hypertension in humans. The results of these studies suggest the existence of an important subgroup of hypertensive patients characterized by increased basal sympathetic tone and reactivity to standing. Such abnormalities could be the result of various dysfunctions, involving the activity of central and peripheral cardiovascular sympathetic fibers, the presynaptic modulation of sympathetic fibers (including the interaction with the parasympathetic system), the inactivation of circulating norepinephrine, and the sensitivity of the efferent cells. The increase in circulating norepinephrine in a group of hypertensive patients seems to reflect a functional increase in the sympathetic tone as shown by the presence of hyperkinetic cardiac functions in hyperadrenergic patients (elevated catecholamine levels), while cardiac functions are normal in normoadrenergic patients (catecholamine levels within normal range). Moreover, the better hypotensive response, combined with normalization of the basal and reactive circulating norepinephrine levels following beta-blockade in hyperadrenergic hypertensive patients, strongly supports the participation of the sympathetic system in the maintenance of hypertension in those patients. The identification and characterization of this subpopulation of patients may be helpful in the development of more rational therapeutic approaches and could eventually permit us to devise better predictors of outcome in hypertension. PMID- 3326697 TI - Difference in sodium sensitivity in human hypertensives. AB - The concept of sodium sensitivity of the blood pressure is discussed in relation to the "early" studies on rigid sodium restriction and the more recent studies on moderate sodium restriction in hypertensive patients. Data on the antihypertensive efficacy of moderate sodium restriction are conflicting, probably as a result of differences in sodium sensitivity of the study populations. Evidence is presented that the renin-angiotensin-aldosterone system and the adrenergic nervous system are important determinants of the blood pressure response to sodium depletion and sodium loading, respectively. The fact that sodium sensitivity is related to age and to the height of the blood pressure limits the therapeutic application of moderate sodium restriction in clinical practice. PMID- 3326698 TI - Electrolyte profiles in a hypertensive population: The Newfoundland Study. AB - Analysis of the electrolyte composition of the diets of 4 population samples in Newfoundland demonstrated: high sodium and low potassium, calcium, magnesium, and zinc contents. It is suggested that these nutritional factors could contribute to the high prevalence of hypertension in this Province. PMID- 3326699 TI - Anti-atherosclerotic effects of calcium antagonists: a brief review. AB - Drugs influencing calcium metabolism in animals fed high-fat diets may modify the progression of atherosclerosis. Agents that enhance calcium transport (catecholamines, vitamin D, parathyroid hormone) may accelerate atherogenesis. Conversely, agents with calcium chelating (diphosphonic acid and thiophene carboxylic acid derivatives), calcium channel blocking (dihydropyridine derivatives, verapamil and its derivatives, diltiazem), and anti-adrenergic (beta blockers) properties have been demonstrated to suppress atherogenesis in rabbits and monkeys. Possible mechanisms of action include lowering of arterial pressure, minor changes in circulating lipoproteins, altered receptor-dependent lipoprotein uptake and lipoprotein metabolism, inhibition of cell migration and cell proliferation, and non-specific protection of injured cells in atheromatous lesions. PMID- 3326700 TI - Electrocardiographic abnormalities and coronary heart disease mortality among hypertensive men in the Multiple Risk Factor Intervention Trial. AB - The Multiple Risk Factor Intervention Trial (MRFIT) was a primary prevention trial involving 12,286 middle-aged men at high risk of future heart attack, about two-thirds of them considered hypertensive at entry. The mortality results suggested an increased risk of coronary heart disease (CHD) death, particularly sudden death, possibly associated with hypertension control, following a stepped care protocol including diuretics, among hypertensive MRFIT special-intervention (SI) participants with abnormalities in their rest ECG. No such adverse association was evident in the usual care (UC) group. ECG data from the Dalhousie ECG program revealed that for nearly every ECG abnormality considered, the risk of CHD death for hypertensive SI men was greater than for hypertensive UC men. The exception to this was ischemic response to exercise, for which the associated relative risk for UC men was 2.96 and for SI men 1.35 (p = 0.03 for SI/UC difference). The risk of CHD death for SI men with any ECG abnormalities compared to those without ECG abnormalities was 3.30. For UC men the corresponding relative risk was 1.22 (p = 0.03 for difference in relative risk). The results suggest that the influence of the presence of ECG abnormalities on the response to hypertension intervention may be heterogeneous, in that certain abnormalities (particularly repolarization abnormalities at rest, and absent or low-amplitude U waves at rest and in post-exercise ECG) may be associated with an adverse response or reduced effectiveness of hypertension intervention, whereas an ischemic ST response to exercise may be associated with a beneficial response to intensive hypertension control efforts. PMID- 3326701 TI - Results of MRC (UK) trial of drug therapy for mild hypertension. AB - The main aim of the trial was to determine whether drug treatment of mild hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates of stroke, of death due to hypertension, and of coronary events, in men and women aged 35-64 years. A total of 17,354 patients was recruited, and 85,572 patient years of observation accrued. Patients were randomly allocated at entry to take bendrofluazide or placebo, or propranolol or placebo. The stroke rate was reduced with treatment (60 strokes, vs 109 in the placebo groups), being 1.4 and 2.6 per 1,000 patient-years of observation, respectively (p less than 0.01), but overall rates of coronary events were not different (222 with treatment and 234 with placebos). The incidence of all cardiovascular events was reduced with treatment (286 events, vs 352 with placebos; p less than 0.05). For rates of mortality from all causes, treatment made no difference. Several post hoc analyses of subgroup results were performed. The all-cause mortality was reduced in men on treatment (157 deaths, vs 181 in placebo groups) but increased in women on treatment (91 deaths, vs 72 with placebos); this difference between the sexes was significant (p = 0.05). The reduction in stroke rate was greater with bendrofluazide than with propranolol (p = 0.002). The rate of strokes was reduced in both smokers and non-smokers taking bendrofluazide, but only in non-smokers taking propranolol; this difference between the drugs was significant (p = 0.03). The coronary-event rate was not reduced by bendrofluazide, whatever the smoking habit, nor in smokers taking propranolol, but it was reduced in non-smokers taking propranolol. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3326703 TI - [A clinico-pathological study of Machado-Joseph disease]. PMID- 3326702 TI - [Immunohistochemical and quantitative observations on pathologic human skeletal muscle fiber--in special reference to complement components and immunoglobulin G reactivities]. PMID- 3326704 TI - Adult hip disease and total hip replacement. PMID- 3326706 TI - Candida vertebral osteomyelitis: report of three cases and a review of the literature. AB - We have recently treated three patients with Candida vertebral osteomyelitis. In each patient there was at least one characteristic prodromal condition, including trauma, multiple antibiotics following bowel surgery, and acute nonlymphocytic leukemia. All patients were treated successfully with amphotericin B. Based on our findings and a review of the literature, we would recommend a 1.0-1.2 gm total dosage of amphotericin B. Alternative therapeutic choices such as 5FC and/or ketoconazole, under specific clinical conditions, have been successfully employed. However, cure can best be confirmed by post-treatment biopsy. PMID- 3326705 TI - Evaluation of a new latex agglutination test for detection of streptococcal antibodies. AB - A liposome-enhanced latex agglutination test (Leapstrep, Cooper Biomedical, Inc., Malvern, PA) was evaluated for its efficacy as a screening test for antistreptolysin O (ASO) and antideoxyribonuclease B (ADNB) antibodies. A total of 179 sera were tested by both Leapstrep and reference ASO and ADNB test methods. The Leapstrep test had a sensitivity of 77% and a specificity of 69% for ASO antibodies when compared to a microtiter adaptation of the Todd-Hewitt ASO tube test. It had a sensitivity of 76% and 75% specificity for ADNB antibodies as compared to the ADNB microtiter enzyme neutralization test. The overall sensitivity of Leapstrep for detecting ASO and/or ADNB antibodies was 73%. The Leapstrep test failed to detect elevated levels of ASO and/or ADNB antibodies in eight patients with streptococcal infections or poststreptococcal sequelae. The Leapstrep test appears to have insufficient sensitivity to be recommended as a screening test for streptococcal antibodies. PMID- 3326707 TI - Nocardial osteomyelitis: a case report and review of the literature. AB - The occurrence of human nocardiosis is increasing in both immunocompetent as well as immunosuppressed patients. A 63-yr-old male construction worker presented with complaints of left hip pain and rapidly enlarging masses on his left neck and chest. He had been treated for a pneumonia of unknown etiology 3 mo prior to admission. A debridement of the left femur was performed and the curetted material was positive for Nocardia asteroides. Osteomyelitis due to the hematogenous spread of Nocardia asteroides is rare, but will undoubtedly be seen with increasing frequency. The literature, as well as 11 reported cases of the hematogenous spread of this organism, are reviewed. PMID- 3326708 TI - Combined testing for antibodies to rubella non-structural and envelope proteins sentinels infections in two outbreaks. AB - Two separate outbreaks of Rubella occurred in Hamilton, Ontario, Canada, 7 yrs apart, with a peak incidence for both in the month of April. A total of 138 cases, 51 in 1978 and 87 in 1985, was observed, the majority being in adolescents and young adults 15-25 years of age. Cases were diagnosed by the presence of Rubella IgM antibody or the combination of a negative passive hemagglutination (Rubacell-Abbott) and a positive enzyme immunoassay (EIA) or hemagglutination inhibition (HI) test on a single serum or by seroconversion for Rubella IgG antibody. Routine screening of sera with the Rubacell test, which measures antibodies to nonstructural rubella proteins together with HI or EIA testing of the negatives, served as a sentinel for rubella infection in the community during both outbreaks. Rubacell antibodies usually appeared 2-3 wk after onset of infections, and when present contained either or both IgG and IgM. Only 8/103 cases had a history of Rubella vaccination. Two of three products of conception yielded rubella virus in cell culture. PMID- 3326709 TI - Comparison of scrape, swab, and cytobrush samples for the diagnosis of cervical chlamydial infection by immunofluorescence. AB - An endocervical swab, cytologic scraper, and endocervical cytobrush were used to prepare simultaneous full-slide smears for immunofluorescence for the diagnosis of cervical chlamydial infection. The cytobrush produced the best sample, with significantly higher numbers of organisms. Most of the false negative results were obtained with the cytologic scraper. The optimum technique appears to be to use a cytobrush sample; however, a swab should be used with pregnant patients. PMID- 3326710 TI - Hemophilus aphrophilus vertebral osteomyelitis: a case report and literature review. AB - We report a 60-yr-old diabetic female who developed vertebral osteomyelitis and discitis due to Hemophilus aphrophilus, and review three previously reported cases of this uncommon infection. Predisposing factors, clinical features, and treatment of H. aphrophilus vertebral osteomyelitis are discussed. PMID- 3326711 TI - Multiple drug-resistance in Shigella flexneri isolated from a patient with human immunodeficiency virus. AB - Persistent shigellosis, due to Shigella flexneri resistant to multiple antibiotics, developed in a 40-yr-old homosexual man with human immunodeficiency virus infection. The Shigella strain demonstrated resistance to ampicillin, tetracycline, and trimethoprim-sulfamethoxazole. Although Shigella flexneri isolates resistant to trimethoprim-sulfamethoxazole are uncommon in the United States, laboratories should monitor resistance patterns through routine in vitro susceptibility testing. PMID- 3326712 TI - Precocious puberty. PMID- 3326713 TI - Management of thyrotoxicosis. PMID- 3326714 TI - Cushing's syndrome: current concepts in diagnosis and treatment. PMID- 3326715 TI - New concepts: growth disorders in children. PMID- 3326717 TI - Controversies in anaerobic infections in childhood. PMID- 3326716 TI - Recruitment experience in clinical trials: literature summary and annotated bibliography. AB - A literature review was conducted to determine what problems exist in accruing adequate numbers of patients for clinical trials. Accrual rates are often not clearly reported, and most studies report that the time period for accrual was extended. Delays in recruitment have an impact on costs and workload throughout the trial. Other problems with the recruitment outcomes include miscalculations in the number of eligible participants in the total population, variations in yield from different types of recruitment sources, and level of community awareness. Planning for recruitment should be part of the overall trial design. Ideally, recruitment planning should be conducted in harmony between the national and local levels. Local community members should be involved. Data-based management of recruitment is necessary and should include a comprehensive data monitoring system with strong administrative support at both central and local levels. Recruitment goals and provisions for corrective action if recruitment lags should be included. Socioeconomic characteristics and attitudes of patients and physicians should be considered in recruitment efforts because they can affect patient participation during all phases of the study. PMID- 3326719 TI - [Pathologic classification of 2659 autopsy cases of congenital heart disease in children]. PMID- 3326718 TI - [Trends of research on the bio-social bases of criminal behavior in foreign countries]. PMID- 3326720 TI - [Serum levels of apolipoprotein CI and CII in 443 cases of healthy adults in Chengdu district]. PMID- 3326721 TI - Hormonal responses during development of streptozotocin diabetes in rats. AB - The pancreatic B-cytolytic agent streptozotocin (STZ) was administered at high and low doses to male Sprague-Dawley rats at the time of weaning (20-30 d). During the next 15 weeks growth, food intake, glycemia and circulating insulin (IRI), glucagon (IRG) and corticosterone (CS) levels were measured at regular intervals. Within seven days after receiving the highest dose of STZ the rats exhibited a severe and persistent diabetes characterized by depressed growth, elevated food intake, insulinopenia and increased concentrations of IRG and CS. With lower doses, a slowly developing hyperglycemia was observed which after a delay of 4 to 6 weeks equalled in severity that of the high dose group. There were also corresponding delays in the appearance of the other major symptoms of the diabetes. Glucose tolerance tests performed 6 weeks after STZ showed that both high and low dose groups were severely glucose intolerant and neither group exhibited an IRI response to glucose challenge. Multiple regression analyses of the hormone levels of individual rats during the developing diabetes revealed that hyperglucagonemia and hyperglycemia arose simultaneously, while insulinopenia was delayed in appearance and only correlated significantly to glycemia late in the experiment. These data suggest that streptozotocin diabetes initially arises from increased glucagon production coupled with a limited capacity of the pancreas to secrete insulin in response to hyperglycemia. Subsequently, the contribution of other factors including continued B-cytolysis, insulinopenia, and elevated adrenal cortical hormones results in the development of the full diabetic syndrome. PMID- 3326723 TI - Development of predictable periapical lesion monitored by subtraction radiography. PMID- 3326722 TI - Tissue response to dental caries. PMID- 3326724 TI - Endodontic-access adhesive bridges. PMID- 3326725 TI - Evaluation of statistics and desirable experimental design of a histomorphometrical method for studies of root resorption. PMID- 3326726 TI - A technique to reinforce weakened roots with post canals. PMID- 3326727 TI - Endodontic failures marked by lack of three-dimensional seal. PMID- 3326728 TI - Chemical diagnosis of inherited defects of fatty acid metabolism and ketogenesis. AB - Urinary organic acid profiles in patients with inherited defects of fatty acid metabolism and ketogenesis are described. Medium-chain acyl-CoA dehydrogenase, short-chain acyl-CoA dehydrogenase, multiple acyl-CoA dehydrogenase, and 3 hydroxy-3-methyl-glutaryl-CoA lyase deficiencies can be recognized at the metabolite level. Data on long-chain acyl-CoA dehydrogenase and systemic carnitine deficiencies are scarce. In the latter disorders, dicarboxylic aciduria is rather nonspecific and points to a modest omega-oxidation of long chain fatty acids. PMID- 3326729 TI - Disorders of lysosomal membrane transport--cystinosis and Salla disease. AB - Two lysosomal storage diseases are now known to result from impaired transport of small molecules across the lysosomal membrane. In cystinosis, the disulfide amino acid, cystine, accumulates and in free sialic acid storage disorders, N acetylneuraminic acid is stored. The lysosomal cystine carrier exhibits saturability, counter-transport, temperature dependence, and stereospecificity; it is highly specific for molecules resembling cystine. Less is known about sialic acid transport, but its temperature dependence and deficiency in certain autosomal-recessive human mutations strongly suggests that it is a carrier mediated process. Cystine and sialic acid serve as prototypes for amino acids and sugars transported by specific lysosomal membrane carriers, whose impairment results in lysosomal storage disorders. PMID- 3326730 TI - Experience with bone marrow transplantation for inborn errors of metabolism. AB - Westminster experience had by 1973 evolved the concept of displacement bone marrow transplantation and extended the donors from matched siblings to other family and unrelated donors. The principles of its use to install donor bone marrow as a component factory for the life of the recipient, together with the importance of immunoprophylaxis are detailed. Satisfying correction has been achieved for 48 previously fatal genetic diseases, partial correction for another 5 with failure for 3 diseases. Displacement bone marrow transplantation is not a panacea, but could be applied to about 7% of known inborn errors, devising in vitro tests which can predict in vivo donor effects, especially since some 80% of our patients are not found in known families and could not have been prevented. PMID- 3326731 TI - Urea cycle disorders, hyperammonemia and neurotransmitter changes. AB - In congenital urea cycle disorders, detoxification of ammonia is impaired, leading to hyperammonemia. Ammonia is the major component causing the acute neurological disturbances. It may influence the supply of substrate and its transport at the blood-brain barrier (BBB) which results in alterations in the synthesis and catabolism of neurotransmitters in the brain. In hyperammonemic rats, the uptake of tryptophan into the brain is increased with an augmented flux through the serotonin pathway. In the forebrain, glutamine as well as amino acids transported with the same L-carrier system, such as phenylalanine, tyrosine and tryptophan, are elevated. It is postulated that the increased transport of tryptophan at the BBB occurs in exchange with glutamine. Methionine sulfoximine (MSO) inhibits glutamine synthetase in the cerebral cortex. The activity drops from 5.85 +/- 0.38 to 1.07 +/- 0.37 mumol/min/g wet weight. Under MSO, the brain tryptophan uptake also decreased to 64.2 +/- 4.5% in hyperammonemic rats, to 54.1 +/- 8.0% in untreated hyperammonemic rats, whereas without MSO an increase of tryptophan uptake was observed. An effect of glutamine on tryptophan transport could also be demonstrated using brain microvessel preparations as a model for the BBB. Our findings indicate that preloading isolated microvessels with L glutamine increases tryptophan uptake into the endothelia when L-glutamine is at concentrations found in brain homogenates under hyperammonemia. Since brain microvessels do not contain glutamine synthetase activity, enzymes from the gamma glutamyl cycle may be involved in the glutamine-mediated tryptophan transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3326733 TI - Recent progress of lysosomal diseases. AB - The majority of lysosomal storage diseases results from genetic inability to express one or another of the many activities of the lysosomal hydrolases. A few lysosomal diseases are caused by a defective transport of certain metabolites across the lysosomal membrane. The recognition of the specific lysosomal defects led to diagnostic tests also for first trimester prenatal diagnosis. The availability of cloned genes for a number of lysosomal enzymes marks the beginning of an understanding of the precise defects responsible for lysosomal storage diseases. PMID- 3326732 TI - Treatment of urea cycle disorders. AB - Recent advances in the treatment of inborn errors of urea synthesis have significantly decreased mortality. Treatment has included combining a high quality low-protein diet with supplements of deficient metabolites and stimulation of alternate pathways of waste nitrogen excretion. Long-term alternate pathway therapy, using sodium benzoate and sodium phenylacetate, has generally been unassociated with signs of toxicity. However, acute intoxications have simulated hyperammonemic crises. Neurologic outcome appears to be primarily a function of duration of neonatal hyperammonemic coma, although ongoing accumulation of urea cycle intermediates may also play a role. Early recognition and treatment are critical if a good outcome is to be possible. PMID- 3326734 TI - Enzymology of the phenylalanine-hydroxylating system. AB - The phenylalanine-hydroxylating system consists of 3 essential components, phenylalanine hydroxylase (PAH), dihydropteridine reductase (DHPR) and the coenzyme, tetrahydrobiopterin (BH4). DHPR and BH4 are also essential components of the trosine- and tryptophan-hydroxylating systems. During the hydroxylation reaction, BH4 is converted to the quinonoid dihydrobiopterin. The reduction of this latter compound back to BH4 is catalyzed by the reductase in the presence of NADH. In addition to the classic form of phenylketonuria, which is caused by a lack of PAH, a form is caused by a lack of DHPR and another by a deficiency of BH4 caused by the lack of an enzyme involved in its de novo biosynthesis. Besides hyperphenylalaninemia, these variant forms are characterized by neurological deterioration. PMID- 3326736 TI - Maternal phenylketonuria. Review with emphasis on pathogenesis. AB - Maternal phenylketonuria (PKU) refers to fetal damage from PKU in the pregnant woman. The progeny from such pregnancies are almost always microcephalic and mentally subnormal and have an increased frequency of congenital heart disease and low birth weight. Treatment with a phenylalanine-restricted diet, if begun before conception, seems to protect the fetus. The degree of protection is much less if dietary treatment is delayed until the pregnancy is in progress. The origin of fetal damage in maternal PKU is not known. Due to placental concentration of amino acids, the fetus is exposed to a higher concentration of phenylalanine than that in the mother, but it is not certain that phenylalanine is the toxic agent. Animal models made hyperphenylalaninemic by the administration of phenylalanine, often accompanied by a phenylalanine hydroxylase inhibitor, do not reproduce the full maternal PKU syndrome; but fetuses and newborns from these models have had reduced growth of the body and brain, and offspring later may show evidence of impaired learning ability. PMID- 3326735 TI - Tetrahydrobiopterin biosynthetic pathway and deficiency. AB - It has been proven that the most common defect in the tetrahydrobiopterin biosynthesis is caused by 6-pyruvoyl tetrahydropterin synthase deficiency. The enzyme 6-pyruvoyl tetrahydropterin synthase consists of four identical subunits which convert dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin in the presence of magnesium. UV, NMR, and MS data prove that the enzyme catalyzes the elimination of triphosphate as well as the intramolecular rearrangement. The 6 pyruvoyl tetrahydropterin synthase activity was measured in fetal erythrocytes and together with the neopterin and biopterin measurements in amniotic fluid this enabled performing prenatal diagnosis of 6-pyruvoyl tetrahydropterin synthase deficiency. Peripheral tetrahydrobiopterin deficiency was shown to be due to an incomplete 6-pyruvoyl tetrahydropterin synthase deficiency or heterozygosity. PMID- 3326737 TI - The cystic fibrosis locus. AB - The identification of the cystic fibrosis locus (CF) provides a model for the study of single gene defects where the biochemical lesion is not known. Using families each of which has several affected siblings, it was possible to exclude a number of 'candidate genes' which had previously been proposed as possible sites of the CF mutation. Exclusion mapping of the genome using polymorphic protein and DNA markers showed that CF is on the long arm of human chromosome 7. The most closely linked flanking markers were identified, and human chromosome fragments containing them (and therefore the CF locus) were isolated in rodent cell lines by chromosome-mediated gene transfer. The transgenome was then analysed using cosmid contig mapping, pulse-field gel electrophoresis, HTF island identification and linkage disequilibrium. In this way, a candidate coding sequence has been identified which always segregates with CF. PMID- 3326738 TI - Molecular basis of isovaleric acidemia and medium-chain acyl-CoA dehydrogenase deficiency. AB - Our early study of isovaleric acidemia (IVA) indicated that isovaleryl-CoA is dehydrogenated by an enzyme that is specific for isovaleryl-CoA. We subsequently identified and purified isovaleryl-CoA dehydrogenase (IVD) and 2-methyl-branched chain acyl-CoA dehydrogenase, which were previously unknown. We also purified and characterized three previously known acyl-CoA dehydrogenases. Five acyl-CoA dehydrogenases share similar molecular features and reaction mechanisms, indicating a close evolutionary relationship. Using the tritium release assay and [35S]methionine labeling/immunoprecipitation, we showed that IVA is due to a mutation of IVD. We also demonstrated that there are at least 5 distinct forms of mutant IVD, indicating an extensive molecular heterogeneity. Furthermore, we cloned cDNAs encoding IVD and medium-chain acyl-CoA dehydrogenases. The comparison of their complete primary sequences revealed a high degree of homology, indicating that these enzymes belong to a gene family, the acyl-CoA dehydrogenase family. PMID- 3326739 TI - Overview of drugs available for ITU sedation. PMID- 3326740 TI - Pneumonia--1987: new developments. PMID- 3326741 TI - Efficacy of oral fluoroquinolones versus conventional intravenous antipseudomonal chemotherapy in treatment of cystic fibrosis. AB - The clinical efficacy of the conventional aminoglycoside plus beta-lactam treatment was compared to that of monotherapy with oral quinolones in 26 adult cystic fibrosis patients in an open prospective clinical trial in which six two week courses of antipseudomonas treatment were administered with an interval of approximately three months between treatments. In each patient two courses of conventional treatment were followed by two courses of quinolone treatment and then by another two courses of conventional treatment. The observed improvements in pulmonary function were somewhat higher when the patients received conventional treatments, and in the most seriously affected patients conventional treatment was significantly better than quinolone treatment. On the basis of these findings it is suggested that quinolone monotherapy cannot replace conventional antipseudomonal chemotherapy in patients with severe pulmonary involvement. PMID- 3326742 TI - Predictive value of surveillance cultures for systemic infection due to Candida species. AB - Weekly fungal surveillance cultures (1,542 cultures) of urine (475), stool (520) and oropharyngeal (547) specimens from 111 patients on the bone marrow transplant and hematologic malignancy services were analyzed. Forty-three percent of the patients were colonized by Candida albicans and 10.8% by Candida tropicalis. There were 22 proven systemic fungal infections, ten due to Candida albicans, eight to Candida tropicalis, one each to Candida pseudotropicalis and Torulopsis glabrata, and two to Aspergillus species. Positive surveillance cultures for Candida tropicalis were highly predictive of systemic infection. The finding of two or more positive cultures yielded high positive predictive values (100%) as a function of body site. Positive surveillance cultures for Candida albicans were not predictive of disease but negative cultures for Candida albicans and Candida tropicalis had a high negative predictive value (95-99%). Surveillance culture data for specific Candida species may aid in diagnostic and therapeutic decision making. PMID- 3326743 TI - Adverse reactions and immunogenicity in adults to regular and increased dosage of diphtheria vaccine. AB - Booster doses of 3 Lf or 7.5 Lf of a regular diphtheria vaccine were given to 200 previously immunized adult volunteers. The toxoid was prepared from toxin with a purity of 2100 Lf/mg protein nitrogen and adsorbed to aluminium phosphate. Systemic reactions were rare and no severe symptoms were observed. Local reactions occurred in 40-50% of the vaccinees, but in only 7.5% were they of clinical significance, i.e. an area of redness/swelling greater than 5 cm. The two doses did not cause significant differences in reaction rates, and the 7.5 Lf dose elicited a better antitoxin response. Thus, a dose of 7.5 Lf diphtheria toxoid of similar purity can safely be given to adults in vaccines. PMID- 3326744 TI - Enzyme immunoassay and enzyme-linked fluoroimmunoassay for detection of Chlamydia trachomatis antigen. AB - An enzyme immunoassay (EIA) and an enzyme-linked fluoroimmunoassay (ELFIA) utilizing monoclonal antibody to major outer membrane protein of Chlamydia trachomatis L2 were developed for rapid detection of chlamydial antigen in clinical samples. The EIA and ELFIA could detect levels of purified chlamydial outer membrane protein as low as 1.0 and 0.2 ng/ml respectively. However, when EIA and ELFIA were compared to chlamydial isolation using 160 patient samples, the sensitivity rate was 68% and 85% respectively. The sensitivity of the antigen detection method might be increased by simply using less diluted samples than in the present study. Chlamydial antigen was also demonstrated by EIA and ELFIA in 15% and 23% of culture-negative samples. The reason for these false-positive findings remains undetermined. PMID- 3326745 TI - Transient fungemia and Candida arthritis due to Candida zeylanoides. AB - A 37 year old man developed transient fungemia caused by Candida zeylanoides following a kidney and pancreas transplant. For the next seven months the patient had signs and symptoms of right knee arthritis. Candida zeylanoides was finally identified as the aetiological agent. Treatment with intravenous amphotericin B was successful. To our knowledge this is the first report of Candida zeylanoides arthritis. PMID- 3326747 TI - Carbohydrate profiling of bacteria by gas chromatography-mass spectrometry: chemical derivatization and analytical pyrolysis. AB - Carbohydrate profiling by gas chromatography-mass spectrometry is a powerful tool for the identification and detection of bacteria. Its increasing applicability in the microbiology laboratory is illustrated by three examples. In the first, differentiation of legionellae by their sugar composition was determined with alditol acetate derivatization followed by selected- ion monitoring. In the second example, a carbohydrate pyrolysis product from Streptococcus agalactiae was used to differentiate group B streptococci from other Lancefield groups after direct sampling from culture plates. The third example employed the carbohydrates rhamnose and muramic acid as chemical markers for the direct detection of bacterial cell wall degradation products in mammalian tissues. The analysis of carbohydrate markers for bacteria by gas chromatography-mass spectrometry has great potential for use in clinical identification of isolated bacteria as well as in the rapid diagnosis of bacterial infections without prior culture. PMID- 3326746 TI - Analysis of dimycocerosates of glycosylphenolphthiocerols in the identification of some clinically significant mycobacteria. AB - Extracts of representative mycobacteria were examined by thin-layer chromatography for glycosylphenolphthiocerol dimycocerosates. The glycolipid typical of Mycobacterium bovis was also found in Mycobacterium africanum and Mycobacterium microti, but it was absent in Mycobacterium bovis AN 5. Mycobacterium gastri strains contained a glycolipid which was chromatographically similar to that in Mycobacterium kansasii. Representatives of Mycobacterium marinum produced a distinct glycolipid type, and one strain had major amounts of a more polar variant. The sugar moieties of purified lipids, including that from Mycobacterium leprae, were identified by thin-layer chromatography of methyl glycosides in acid methanolysates. PMID- 3326749 TI - Historical dateline of cancer control in Delaware. PMID- 3326748 TI - Stereoselective inhibition of chloride transport by loop diuretics in pancreatic beta-cells. AB - The effects of loop diuretics on 36Cl- uptake was tested in isolated beta-cell rich pancreatic islets. Bumetanide reduced the 36Cl- influx and the levorotatory form of ozolinone reduced both the influx and equilibrium content of 36Cl- in the islets, whereas the dextrorotatory form was largely inactive. The data suggest that the beta-cells are equipped with a loop diuretic-sensitive system for 36Cl- uptake and that this system is confined to a sterically well-defined structure. PMID- 3326750 TI - Progress towards a malaria vaccine. PMID- 3326751 TI - Antiparasitic agents. Part 7--Antimalarial activity of alkyl 5(6)-(4-aminophenyl) sulphonobenzimidazole-2-carbamates. PMID- 3326752 TI - Studies on the comparative gametocytaemia of P. berghei (NK 65) in male and female Mastomys natalensis. PMID- 3326754 TI - Detection of Plasmodium vivax in human blood using synthetic DNA probe. PMID- 3326753 TI - Effect of zinc diet on xanthine oxidase activity of liver of mice infected with Plasmodium berghei. PMID- 3326755 TI - Dynamics of P. falciparum ratio--an indication of malaria resistance or a result of control measures? PMID- 3326756 TI - Report of a case of P. falciparum malaria resistant to chloroquine and combination of sulfalene and pyrimethamine in Delhi. PMID- 3326757 TI - A review of fixed phagocytic and pinocytotic cells of decapod crustaceans, with remarks on hemocytes. AB - Clearance of foreign materials from the hemocoel of decapod crustaceans involves several distinct kinds of cells. Proteins, and possibly viruses below 30 nm diameter, are known to be removed by the branchial podocytes, which are specialized pinocytotic nephrocytes located in the gills. These cells, and podocytes of the antennal gland (excretory organ) which may also be of importance in clearance, are similar to podocytes of Bowman's capsule of the vertebrate kidney. Phagocytic clearance of particulate material (with possible exception of the small viruses) is accomplished by three kinds of cells, one free and the other two fixed to tissues facing hemal spaces. The hemocytes, free cells suspended in the hemolymph, are the most abundant and generalized of these phagocytic cells. Phagocytic reserve cells are applied to myofibers in the heart of penaeid and palaemonid shrimp, and probably the same as reserve cells found throughout the hemocoel of all decapods. They are minimally involved in clearance of injected carbon and carmine, but are not known to phagocytize naturally occurring particles such as bacteria or viruses. The fixed phagocytes are very important in the clearance of some substances. They are located on the exterior surfaces of arterioles in hemal spaces of the hepatopancreas. They are highly specialized cells designed to sequester large amounts of various types of particulate matter, not only through phagocytosis but by trapping and retaining vast numbers of particles within a net- or sievelike layer of granular material which surrounds the free surface of the fixed phagocyte. Derivation, morphology, development, and function of the above cell types are described and discussed. PMID- 3326758 TI - Phylogeny of lymphocyte heterogeneity: identification and separation of functionally distinct subpopulations of channel catfish lymphocytes with monoclonal antibodies. AB - The purpose of this study was to identify monoclonal antibodies reactive with channel catfish T cells. Since a variety of commercially available anti-human and mouse T cell reagents failed to react with channel catfish leucocytes, the development of anti-fish T cell monoclonal antibodies was undertaken. One of these reagents, designated mAb 13C10, reacted with channel catfish surface immunoglobulin negative, but not positive, lymphocytes. This reagent, when used in "panning" protocols, was able to isolate those channel catfish lymphocytes which provide helper activity for antibody synthesis to a thymus dependent antigen. In addition, this antibody was observed to react with most thymocytes, neutrophils, and thrombocytes, few hepatocytes, and with some brain cells (possibly neurons). It was concluded that this antibody reacts with relatively high molecular weight antigens on channel catfish T cells and that it may be a pan anti-T cell reagent (possibly akin to Thy-2) for this species. PMID- 3326759 TI - Accuracy of stone, epoxy and silver plate-acrylic models. PMID- 3326760 TI - Tensile bond strengths of resin luting cements for resin-bonded bridges to etched enamel. PMID- 3326761 TI - Relationship between surface-free energies of dental resins and bond strengths to etched enamel. PMID- 3326762 TI - Crown retention: a comparative study of core type and luting agent. PMID- 3326763 TI - The effect of fatigue impact forces upon the retention of various designs of resin-retained bridgework. PMID- 3326764 TI - Influences on the bulk fracture incidence of amalgam restorations: a 7-year controlled clinical trial. PMID- 3326766 TI - A new dental Pd-Co alloy for ceramic veneering. PMID- 3326765 TI - The control of marginal microleakage in amalgam restorations using a dentin adhesive: a pilot study. PMID- 3326768 TI - The effect of storage solutions and mounting media on the bond strengths of a dentinal adhesive to dentin. PMID- 3326767 TI - Bonding agent strengths with processed composite resin veneers. PMID- 3326769 TI - Concentration of solutions for electrolytically etching Rexillium III. PMID- 3326770 TI - Delayed hygroscopic expansion of phosphate-bonded investments. PMID- 3326771 TI - Gold-based bonding agents between palladium-alloys and ceramic veneer. PMID- 3326772 TI - Forces fracturing cements at die interfaces and their dependence on film thickness. PMID- 3326773 TI - Microleakage and bond strength of resin restorations with various bonding agents. PMID- 3326774 TI - A clinical study of the composite/bonding resin-tooth interface. PMID- 3326775 TI - Effects of saliva contamination and phosphoric acid composition on bond strength. PMID- 3326776 TI - Effect of 5% sodium hypochlorite or Tubulicid pretreatment in vivo on the marginal adaptation of dental adhesives and glass ionomer cements. PMID- 3326777 TI - Casting of dental alloys: mold and alloy temperature effects. PMID- 3326778 TI - Bond strength of dentinal bonding agents to chemomechanically prepared dentin. PMID- 3326779 TI - In vitro measurement of vertical denture displacement by denture adhesives. PMID- 3326780 TI - Zinc, impaired immunity, and oral disease in the geriatric patient. PMID- 3326783 TI - [Genetic analysis of the polyauxotrophy of the early mitotic progeny of Saccharomyces cerevisiae zygotes. III. The behavior of the chromosome-III markers in polyauxotrophic clones and their mitotic and meiotic segregants]. AB - Cloning and segregation analysis of polyauxotrophic (PA) progeny, as well as the study of diploid segregants, revealed an unusual state of the diploid genome in these strains. Analysis of linkage markers of chromosome III in all crosses may be expected to illuminate relationships between the homologous chromosomes. All PA strains were assigned to two major classes. In the class of PA strains with recombinant chromosome III, the effect of approachment of third linkage markers was noted. In other strains, transposition of genetic marker metA1 to chromosome III and its linkage to leu2 were discovered. The present study has demonstrated that the unusual state of the diploid genome of PA strains induces multiple nonspecific alterations in chromosome relationship and structure. It is likely that these alterations are the consequence of disturbance in mitotic apparatus of cell. PMID- 3326782 TI - An elderly patient with iatrogenic damage from repeated scaling. PMID- 3326781 TI - Effect of denture stability, retention, and tooth form on masticatory function in the elderly. PMID- 3326784 TI - [Genetic study of plasmid integration into yeast chromosomes. VI. Patterns of the destabilization of chimeric chromosomes and their use in gene mapping]. AB - The 2 microns DNA-dependent destabilization of yeast chimeric chromosomes III, IV, V was analysed. The comparison of its peculiarities with the earlier localized sites of episomal plasmid integration allowed to derive genetic regularities of destabilization process. Two destabilization rules that describe patterns of the loss of genetic information in the chromosome were formulated. The usefulness of this for mitotic intrachromosomal gene mapping in yeast was demonstrated using plasmid integration site mapping in chromosome I. PMID- 3326785 TI - [Chromosome stability in saccharomycete yeasts]. AB - Mutants with high instability of chromosome III designated Chl+ (chromosome loss) were obtained after irradiation with UV the Z4221-3c1 haploid disomic for chromosome III. The Chl+ mutants can be divided into two classes: 1) CL2, CL3, CL7, CL9, CL11, CL12, CL13 with elevated level of spontaneous inter- and intragenic recombination; 2) CL4, CL8 which unstable maintenance of chromosome III not accompanied with elevation of mitotic recombination frequency. The CL4 and CL8 mutants also reveal, in contrast to other mutants, unstable maintenance of artificial mini-chromosomes with chromosomal replicator ARS1 and centromeric loci CEN3, CEN4, CEN5, CEN6, CEN11. Substitution of ARS1 for other yeast replicators (ARS2, ARS of 2 micron plasmid) leads to no stabilization of mini chromosomes in mutants. The noncentromeric plasmids containing homologous replicator (or replicators) from Candida maltosa are maintained with the same frequency both in wild type and in mutants. So, the stability of mini-chromosomes in CL4 and CL8 is not connected with uneffective replication of these chromosomes. Instability of chromosome III and mini-chromosomes in CL4 and CL8 is controlled by two nonallelic genes designated chl14 and chl18. We suppose that these genes control the process of centromere interaction with mitotic spindle microtubules. PMID- 3326786 TI - Determination of the nucleotide sequence for the glutamate synthase structural genes of Escherichia coli K-12. AB - We have determined the complete nucleotide sequence of a 6.3-kb chromosomal HpaI EcoRI fragment, that contains the structural genes for both the large and small subunits of the Escherichia coli K-12 glutamate synthase (GOGAT) enzyme, as well as the 5'- and 3'-flanking and intercistronic DNA regions. The Mrs of the two subunits, as deduced from the nucleotide (nt) sequence, were estimated as 166,208 and 52,246. Partial amino acid sequence of the GOGAT enzyme revealed that the large subunit starts with a cysteine residue that is probably generated by a proteolytic cleavage. Northern blotting experiments revealed a transcript of approximately 7300 nt, that at least contains the cistrons for both subunits. A transcriptional start point and a functional promoter were identified in the 5' DNA flanking region of the large subunit gene. The messenger RNA nontranslated leader region has 120 nt and shares identity with the leader regions of E. coli ribosomal operons, in particular around the so-called boxA sequence implicated in antitermination. Other possible regulatory sequences are described. PMID- 3326788 TI - Indirect bonding procedure for laminate veneers. A dental adjunct to esthetic surgery. PMID- 3326787 TI - Allele-specific complementation of an Escherichia coli leuB mutation by a Lactobacillus bulgaricus tRNA gene. AB - A Lactobacillus bulgaricus gene encoding a serine tRNA with the anticodon CGA was isolated from a L. bulgaricus clone bank and characterized. This gene is expressed and active in Escherichia coli. The wild-type form of the gene allele specifically complements the E. coli leuB6 mutation. This process depends on gene copy number; high copy number restores leucine prototrophy, while low copy number does not. We suggest that restoration of activity of the mutant leuB6 allele occurs by missense suppression. The L. bulgaricus tRNA(CGASer) when overproduced in E. coli is misacylated at a low frequency, leading to the insertion of an amino acid other than serine in response to the presumed mutant codon UCG in the leuB6 gene. Nucleotide (nt) sequences flanking the tRNA coding region are present in the L. bulgaricus tRNA gene, closely resembling E. coli promoter and terminator elements. A noteworthy feature of this tRNA gene is the extreme length (22 nt) of its extra arm. The 3'-terminal CCA of the tRNA is not encoded in this tRNA gene and thus must be added posttranscriptionally. PMID- 3326790 TI - Mandibular reconstruction after cancer surgery. PMID- 3326789 TI - The radiant smile. PMID- 3326791 TI - Effective use of the team approach in facial malignancy. PMID- 3326792 TI - Moh's surgical treatment and reconstruction of lesions near the lip. PMID- 3326793 TI - Methods of therapy and reconstruction of malignant auricular neoplasms. PMID- 3326794 TI - Moh's surgical treatment and reconstruction of cutaneous malignancies of the nose. PMID- 3326795 TI - Moh's surgical treatment and reconstruction of lesions in the medial orbit. PMID- 3326796 TI - Parallel histologic sections for head and neck mucosal cancer. PMID- 3326797 TI - Energy and protein relations in the broiler. 5. Lipogenesis, glucose production and metabolic hormone levels as functions of age and dietary protein levels. AB - Both a decrease in the dietary carbohydrate level and an increase in the protein level decrease lipogenesis in chicks. Interpreting results of previous experiments can be confounded by alterations in the quantity of carbohydrate because as protein was added to the diets used in these studies, carbohydrate was decreased. In the present study, diets containing 13, 16, 19 or 23% protein and 70% carbohydrate calories were fed to Ross male chicks from 1 to 4 weeks of age to determine the effect of dietary protein level (% crude protein) on growth and intermediary metabolism in 2, 3, and 4-wk old chicks. All treatment groups were limited to that amount of feed consumed by the 23% protein group. There were no significant differences in body weights among the treatment groups at 4 wk of age. An increase in dietary protein (23 vs. 13%) increased (P less than 0.05) in vitro glucose production by liver slices from 4-wk old chicks. In contrast, the same increase in dietary protein decreased (P less than 0.05) in vitro lipogenesis by liver slices from 2, 3, and 4-wk old chicks. The same increase in dietary protein increased (P less than 0.05) both insulin (INS) and thyroxine (T4) and decreased (P less than 0.05) triiodothyronine (T3). Serum T3 and T4 concentrations were less (P less than 0.05) and INS concentrations were greater (P less than 0.05) in 4-wk old chicks compared to 2-wk old chicks. PMID- 3326798 TI - [Combined insulin-sulfonylurea in type II diabetes mellitus--an update]. PMID- 3326799 TI - [The aging process--facts and theories]. PMID- 3326800 TI - [Prevention of eye scarring by 5-fluorouracil]. PMID- 3326801 TI - [Organic acidemias: clinical, laboratory and therapeutic approach]. PMID- 3326802 TI - [The cough as a challenge]. PMID- 3326803 TI - [Ribavirin in viral bronchiolitis]. PMID- 3326804 TI - [Tinea pedis]. PMID- 3326805 TI - [The laser in urology]. PMID- 3326806 TI - [Vaccine for AIDS--obstacles and approaches to solutions]. PMID- 3326807 TI - [Shoulder dystocia--the obstetrician's nightmare]. PMID- 3326808 TI - [Continuous passive motion in the treatment of joint injuries]. PMID- 3326809 TI - [The temporomandibular disorders--etiology and management]. PMID- 3326810 TI - [Nonrespiratory tuberculosis]. PMID- 3326811 TI - [Novel aspects of natural killer cell function: regulation of immune response and hematopoiesis]. PMID- 3326812 TI - MODY--a model for understanding the pathogeneses and natural history of type II diabetes. PMID- 3326813 TI - Urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) excretion and its relation to plasma renin activity in hyperthyroidism. PMID- 3326814 TI - S-100 protein: a prognostic indicator in cutaneous malignant melanoma? AB - A series of 215 cases of cutaneous malignant melanoma referred to a single department of clinical oncology between 1940 and 1969 was studied to assess the accuracy of the Breslow thickness and the role of S-100 protein in predicting the clinical prognosis. Histological examination of these tumours showed that although the Breslow thickness correlated well with prognosis, in a significant number of cases it did not reliably forecast clinical outcome. From this series, tissue from those patients who survived disease-free for more than 10 years and those who died within a year of diagnosis was stained immunohistochemically for S 100 protein. Contrary to the findings of earlier studies, strong staining for S 100 protein was associated with improved survival (P less than 0.001). A marked increase in the incidence of cutaneous malignant melanoma was noted during the period of the study. PMID- 3326815 TI - The contribution of immunohistochemical staining in tumour diagnosis. AB - With the increasing use of immunohistochemical stains in the diagnostic laboratory, it becomes relevant to review the contributions of this new technology in the area of tumour diagnosis. During 1986, our laboratory received 21,479 biopsy specimens of which 2013 were tumours. Nine hundred and fifty-eight tumours (47.5%) were subjected to immunohistochemical analysis. The biopsy and immunohistochemistry reports of 200 consecutive tumours, including 41 consultation cases, were retrospectively reviewed and assigned to one of the five categories. Immunohistochemical stains confirmed the preferred H & E diagnosis in 106 cases (53%); made the definitive diagnosis from a list of differential diagnosis in 29 cases (14.5%); provided contributory information in 36 cases (18%); were non-contributory in 27 cases (13.5%); and rendered an unsuspected diagnosis in two cases (1%). Immunohistochemical stains were particularly useful in distinguishing between malignant lymphoma and anaplastic carcinoma and in the identification of amelanotic melanoma. The application of a panel of antibodies chosen in accordance with the differential diagnoses considered was very useful in the typing of anaplastic round cell and spindle cell tumours. In 27 cases (13.5%), immunohistochemical stains were non-contributory. About half of these were referred cases and the failure to demonstrate the relevant antigens in normal tissues which served as in-built controls suggested that part of the problem may be due to differences in methods of fixation which led to sub-optimal preservation of tissue antigens. We conclude that immunohistochemical stains provide important and sometimes essential information for definitive typing of anaplastic tumours. Often the information derived was of therapeutic and prognostic relevance. We argue that this is a cost-effective test although we would caution that in all circumstances the interpretation of immunostaining must be made in the context of the histological as well as the clinical and laboratory data. PMID- 3326817 TI - Cells containing factor XIII subunit a in benign and soft tissue tumours. PMID- 3326816 TI - Adenocarcinoma of the endocervix--a histochemical study. AB - The histological distinction between endometrial and endocervical adenocarcinoma may present diagnostic difficulties. Several reports have suggested that differences in the histochemical staining of the tumours may indicate their histogenesis. In this paper we have compared the staining properties of 20 endocervical adenocarcinomas (14 invasive and six in situ) with 12 cases of endometrial adenocarcinoma. Unequivocal examples were used where the site of origin was not in doubt. Sections were stained using a monoclonal antibody to carcinoembryonic antigen (CEA), alcian blue at pH 1.0 and pH 2.5, PAS-diastase and toluidine blue. The results were graded by two pathologists and results compared. Three poorly differentiated invasive endocervical tumours were completely negative for CEA. Seventeen out of the remaining 20 endocervical tumours and 7/12 endometrial adenocarcinomas showed a non-specific apical staining pattern. This also occurred in normal and dysplastic endocervical glands. Intense intracytoplasmic staining for CEA was found in 7/14 invasive and 3/6 in situ endocervical adenocarcinomas. Normal endocervix never showed this staining reaction. However, 4/12 endometrial tumours showed a similar pattern. Mucin stains showed no specific staining pattern for either tumour. In an individual case where the site of origin is in doubt, histochemical methods are of little value in confidently resolving the problem. PMID- 3326818 TI - L3T4 and the immunoglobulin gene superfamily: new relationships between the immune system and the nervous system. AB - L3T4 is a mouse cell surface protein expressed on most thymocytes and on the subset of mature T cells that recognizes class II MHC molecules. Its primary function on T cells is most likely that of increasing the avidity of the interaction between T cells and antigen-presenting or target cells. It may accomplish this by binding to a nonpolymorphic region on class II MHC molecules. The cDNA and gene encoding L3T4 have been isolated and sequenced. Analysis of the amino acid sequence predicted by the nucleotide sequence indicates that L3T4 is a member of the Ig gene superfamily. It is most closely related to Ig and Tcr V regions. Although the amino-terminal domain of L3T4 is the portion of the molecule that is most similar to V-regions, L3T4 is one of the polydomain members of the Ig gene superfamily. Studies of the expression of L3T4 mRNA in various tissues led to the surprising finding that this gene is transcribed not only in T lymphoid cells, but also in brain. The predominant form of L3T4 mRNA expressed in brain is foreshortened as compared to that in T lineage cells, and it is most likely the product of a distinct transcriptional start site. If translated, the protein encoded by this brain transcript would be 217 amino acids in length and would lack the signal peptide and the amino-terminal 214 amino acids of the mature protein. It is not known whether a stable protein product is synthesized from this mRNA or what its function might be. However, these findings place L3T4 in an intriguing class of Ig gene superfamily members characterized by coexpression in the immune system and the nervous system. PMID- 3326820 TI - Immune-mediated encephalitis: on the role of antigen-presenting cells in brain tissue. PMID- 3326819 TI - CAMs and Igs: cell adhesion and the evolutionary origins of immunity. AB - The lymphoid system and cells of immunity are as morphologically well defined as those of any complex organ but in addition they show dynamic long-range interactions between the fluid tissues (lymphocytes, monocytes, etc.) and the solid, vascular and generative tissues and organs which they comprise. Given the observation that CAMs are present in epithelial components of lymphoid organs, it appears that, in their ontogeny, the organs of immunity will share a common principle of morphoregulation by CAMs with brains, feathers and other parts of the phenotype. As discussed here, this principle is a regulatory one operating across many levels of organization from the genes to tissues and back again (see Fig. 1). At some early point in the evolution of the immune system, a gene corresponding to an N-CAM precursor must have duplicated to provide a basis for the Ig superfamily with its increasing specializations for recognition and for cellular regulation during the immune response. Lymphocyte cellular families also developed later specializations (along with other leukocytes) for adhesive functions accessory to specific recognition. As far as we can see, the molecules for these accessory functions only remotely resemble CAMs, but closely resemble receptors for matrix molecules and SAMs. What CAMs and Ig superfamily members have in common is an evolutionary path and important roles in mediating complex regulatory responses that arise from cell-cell interactions. In the one case, this regulation leads to morphology, and in the other, to immune recognition. The first depends directly upon pattern (the formation of definite tissue structure); the regulation of the second also depends upon pattern to the extent that its function is dependent upon the morphology of lymphoid organs and vasculature. But although specific immune recognition depends locally upon adhesion through special mechanisms, it does not lead to morphology. One must not therefore impute too much in the physiological sense to the resemblance among brain molecules and molecules of the immune system. CAMs themselves are not directly histotypic at the level of individual differentiated cells but rather are used to link early tissue boundaries in induction and function in a wide variety of different tissues. As a consequence, N-CAM is central to the formation and maintenance of neural tissue but has a much wider tissue distribution and a fundamental role in very early embryogenesis as is the case with other primary CAMs. Thus, the immune system did not evolve from the nervous system, but from a cell adhesion system essential to both.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3326821 TI - Neuroleukin: basic biology and functional interaction with human immunodeficiency virus. PMID- 3326823 TI - A molecular genetic approach to the identification of genes expressed predominantly in the neuroendocrine and immune systems. AB - Our results demonstrate that expression of neuropeptide tyrosine, one of the most abundant and widespread peptides in the mammalian nervous system, occurs in non neuronal cells, in keeping with the emerging view that neuropeptide synthesis is not restricted to cells of the nervous system. RNA blot analyses and radioimmunoassays detected both NPY mRNA and NPY peptide in rat and mouse spleen, bone marrow, and peripheral blood cells. Immunohistochemical staining of sections from rat bone marrow with an NPY-specific antiserum revealed NPY-like immunoreactivity in megakaryocytes. In situ hybridization confirmed that the NPY like peptide detected in megakaryocytes was synthesized de novo from NPY mRNA present in these cells. Megakaryocytes, the platelet-forming cells, originate from pluripotent hematopoietic stem cells present in the bone marrow as well as in the spleen of rodents. During microvascular damage, platelets aggregate at the damaged site and release bioactive substances. NPY is known to be a potent vasoconstrictor. Therefore, we propose that megakaryocyte-derived NPY is stored in platelets and released during platelet aggregation, resulting in a long lasting vasoconstriction. Greatly elevated levels of megakaryocyte-derived NPY, as compared to the level found in BALB/C mice, were found in several mouse strains (NZB, NZB x W, and BXSB) which develop an autoimmune disease resembling systemic lupus erythematosus. Whether the elevation of megakaryocyte-derived NPY plays a role in the autoimmune disease progression in these mice or whether it merely reflects a related hematopoietic abnormality remains to be determined. Subtractive hybridization was used to isolate two cDNA clones that are predominantly expressed in the brain and the immune system. These and similarly derived cDNA clones will be used as molecular probes to study the mechanisms governing tissue-specific expression in the nervous and immune systems. Discovering the function of the proteins encoded by such cDNA clones may reveal evolutionary mechanisms shared by the nervous and immune systems, as well as a molecular basis for the interaction between these systems. PMID- 3326822 TI - Noradrenergic sympathetic neural interactions with the immune system: structure and function. PMID- 3326824 TI - T cells in multiple sclerosis and inflammatory central nervous system diseases. AB - Using murine monoclonal antibodies to mark total T cells, we have found rapid migration of T cells into the CSF in progressive multiple sclerosis patients, suggesting that the ongoing inflammatory responses in the CNS may depend on the continued movement of cells from the periphery into the target organ. Cloning experiments have indicated that the T cells present in the CSF during viral and post-viral encephalomyelitis represent sequestered populations of antigen specific cells. In more chronic disease processes, these cells may also have restricted clonality as measured by the frequency of different T-cell receptor gene rearrangements on Southern blotting. It is known that there is restricted clonality of the B-cell immunoglobulin response in the CSF compartment with inflammatory CNS diseases, and with infections the majority of these so-called oligoclonal antibodies are directed against the exciting antigen and are synthesized in the CNS. Although we believe that T cells in the CNS originate from the blood, during the course of an inflammatory response the antigen and clonally-restricted populations found in the CSF may represent either selective migration or selective accumulation in the CNS. Selective migration might occur at the endothelial barrier as these cells can express Class II MHC antigens and act as antigen-presenting cells in the CNS (McCarron et al. 1985). Selective accumulation of T cells in the CNS might occur after non-specific migration of cells into the CNS followed by proliferation and expansion of T cells that have been induced by antigens in the brain. Antigen-presenting cells that are present in situ, such as astrocytes, may also play a role in the selective expansion of T cells in the CSF (Fontana et al. 1984). Alternatively, it is possible that T cells are induced to expand in the target CNS tissue non-specifically, e.g., via the CD2 pathway. In this regard, we have observed that CSF T cells exhibit alterations in stimulation by anti-T112 + anti-T113 monoclonal antibodies. The mechanism of damage to CNS tissue by immune cells is essentially unknown. For example there are no clear links between antibodies present in the CNS and CNS damage in SSPE where high titers of anti-measles antibodies are present. Whereas we did not observe high frequencies of measles-reactive cells in the CSF of a subject with SSPE, we did observe MHC non-restricted cytotoxic T cells which expressed TCR-gamma chains rather than alpha-beta chains.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3326826 TI - The immune logical brain. PMID- 3326825 TI - Neuropeptide regulation of mucosal immunity. PMID- 3326828 TI - The 100th volume of Immunological Reviews. PMID- 3326827 TI - Immunological studies of the diversity and development of the mammalian visual system. PMID- 3326829 TI - Sir Peter Medawar, 1915-1987. PMID- 3326830 TI - Effect of physical work during pregnancy on birth weight. PMID- 3326832 TI - Chronic myelogenous leukemia of childhood. PMID- 3326833 TI - Hodgkin's disease. PMID- 3326831 TI - Short-term diazepam prophylaxis in febrile convulsions--a new approach. PMID- 3326834 TI - Advances in management of non-Hodgkin lymphoma. PMID- 3326835 TI - Bone marrow transplantation in India. PMID- 3326836 TI - Brain tumors. PMID- 3326838 TI - Enteropathogenic Escherichia coli diarrhea in hospitalized children at Delhi. PMID- 3326839 TI - Etiological factors and perinatal risks in symmetrical and asymmetrical intrauterine growth retardation. PMID- 3326837 TI - Oncogenes and their role in human neoplasia. PMID- 3326840 TI - Tumors of the liver, other than primary hepatocellular carcinoma. AB - Hepatic angiosarcoma is the second most common primary malignant neoplasm of the liver. Although comprising only 2 per cent of all hepatic primary tumors, it represents a major clinical problem because of its strong association with industrial vinyl chloride exposure and its incurability. Strict ceilings on the amount of exposure for vinyl chloride workers has reduced the incidence of this devastating tumor. In addition, recent chemotherapeutic trials have provided both improved performance status and prolonged survival in several patients. PMID- 3326841 TI - Mistakes in treatment of accident cases before reaching hospital. PMID- 3326842 TI - Ceramics: their place in dentistry. AB - A transfer molded ceramic coping material, Cerestore, and a castable ceramic, Dicor, are commercially available for fabrication of all-ceramic crowns. The manufacturers indicate their use should be in single unit anterior or posterior crowns. Tooth preparations are similar and should have rounded lines angles to avoid sharp points which may cause stress concentration. The amounts of tooth reduction are also similar and range from 1.0 to 2.0 mm depending on the location of surfaces. There are variations in fabricating procedures but both involve heat treatment and special equipment. Cerestore requires eventual veneer build-up and shading. Dicor requires surface shading. Both are evaluated and classified by the Council on Dental Materials, Instruments and Equipment of the American Dental Association. At least three other ceramic systems are being developed but are not yet commercially available. PMID- 3326843 TI - Role of the general practitioner in data collection and cross matching. AB - Dental records used in identification procedures are most often obtained from the offices of general practitioners. The family dentist is required to provide accurate and well documented data to assist in the identification process. The forensic team participating in a mass disaster identification may also utilize the services of general practitioners. They play an active role in the oral autopsy, the oral radiographic procedure, and the identification process itself. PMID- 3326844 TI - The diagnostic properties of laboratory tests for rabies. AB - We have prospectively followed 915 victims bitten by 664 dogs between January 1984 and December 1985 to assess death and severe neurological disability. These dogs were brought either by the owner or bite victims to Ta Pra Diagnostic Centre for detection of rabies. Each patient was followed every three months by mail for at least one year after the bite. In addition, intensive follow-up in the community was undertaken on 235 patients who failed to respond to mail follow-up, all 23 who reported events as well as 523 of the 720 mail-responders. Hospital records were examined for all patients requiring treatment. All patients with non fatal events were also examined at the university hospital. Blind independent comparison of the three diagnostic tests (Sellers stain, fluorescent antibody test and mouse inoculation test) for the presence or absence of rabies in animal brains were performed to assess the accuracy of local routine diagnostic test methods. In case of disagreement between test methods, the result on mouse inoculation was considered definitive for the presence or absence of rabies. Test results were mailed to all victims. Seven hundred and twenty out of 955 subjects responded to the mail follow-up giving a response rate of 75.4%. Intensive follow ups were successful in all subjects who responded. Of 235 subjects who did not respond to the mail follow-up, only 195 (83%) were located. The remaining 40 bite victims who did not respond to mail follow-up and could not be located were all bitten by animals who did not have rabies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3326845 TI - Relationship of body fat distribution to the metabolic clearance of insulin in premenopausal women. AB - The effects of body fat distribution on the metabolic clearance rate of insulin (MCR) and its relationship to peripheral insulin sensitivity (M/I) and androgenic activity were assessed in six nonobese and 20 obese premenopausal women with varying waist-to-hip girth ratio (WHR). As an index of androgenic activity, plasma levels of the sex hormone binding globulin (SHBG) and percentage free testosterone (%FT) were determined. The mean MCR in the obese and nonobese groups were similar (571 +/- 29 vs 578 +/- 31 ml/min/m2). Within the obese group, MCR varied between 401 and 822 ml/min/m2 and was inversely correlated with the WHR (r = -0.50, P less than 0.05). The reduction in MCR with upper body fat localization was observed at both sub- and supra-maximal plasma insulin levels. MCR correlated negatively with fasting and postglucose challenge plasma insulin levels and positively with M/I. MCR also correlated with plasma SHBG and %FT levels. We conclude that upper body fat localization is associated with diminished insulin clearance. This diminution is closely aligned with the degree of peripheral insulinemia and insulin sensitivity. The increase in androgenic activity may contribute to the aberrant insulin clearance observed in upper body obese subjects. PMID- 3326846 TI - Drug treatment of obesity: an overview. PMID- 3326847 TI - A pharmacotherapeutic approach to the regulation of hyperinsulinemia and obesity. AB - A selective inhibitor of thromboxane synthase, Ro 22-3581 has been shown to be a useful tool for investigating the relationship between hyperinsulinemia and obesity. These studies have established that the pharmacologic normalization of the hyperinsulinemia associated with elevated weights in genetically obese and diet-induced obese rats resulted in decreased weight gain or weight loss. This effect was shown to be reversible, partially independent of the suppression of food intake, dependent on a functional endocrine pancreas, and not diabetogenic. However, these studies have not established a cause and effect relationship between the inhibition of thromboxane synthase activity by Ro 22-3581 and its suppression of insulin secretion and circulating insulin levels. PMID- 3326848 TI - Differential effects of sugars and the alpha-glucosidase inhibitor acarbose (Bay g 5421) on satiety in the Zucker obese rat. AB - To examine the satiety responses of Zucker obese and lean rats to simple sugars, adult male rats were given equicaloric intragastric infusions of fructose, glucose, and sucrose. All three sugars reduced the short-term intakes of both genotypes, although no reliable between-genotype differences in the satiety effects of the sugars were observed. Within each genotype, fructose had a larger satiety effect than sucrose. To examine a potential basis for the observed effects, rats were given sucrose infusions containing the intestinal glucosidase inhibitor acarbose (Bay g 5421). In obese rats, addition of a low dose of acarbose increased the satiety effect of sucrose infusion. Delaying carbohydrate absorption via acarbose administration may alter gastrointestinal and/or postabsorptive satiety processes, and may prove useful as a probe for investigating the nature of satiety signals. PMID- 3326849 TI - Insulin binding and glucose transport in adipocytes of acarbose-treated Zucker lean and obese rats. AB - The intestinal glucosidase inhibitor acarbose was administered as a dietary admix (30 mg/100 g chow diet) to male Zucker obese and lean rats. After 15 weeks, epidiymal fat pads were removed and adipocytes isolated by collagenase digestion. Equilibrium binding of A-14 tyrosine 125I-insulin, and transport of U-14C-glucose was determined was adipocytes incubated for 50 min at 37 degrees C in 0-16000 pM insulin. Insulin binding/cell was enhanced two-fold in lean (P less than 0.01) and obese (n.s.) drug groups. In drug-treated leans, increased sensitivity of glucose transport to submaximally stimulating concentrations of insulin was observed (P less than 0.02). For both genotypes, acarbose mildly decreased insulin levels and body weight gain, although adipocyte size was unaffected. Results indicate that enhanced insulin binding accompanies metabolic improvements induced by acarbose in lean Zucker rats. PMID- 3326850 TI - Nutrient balance: new insights into obesity. AB - This overview of nutrient balance suggests the following general conclusions. Nutrient balance is in part regulated by the two limbs of the autonomic nervous system. Hypothalamic and genetic obesity are associated with lower levels of sympathetic activity. Conversely the reduced weight of animals with lateral hypothalamic lesions is associated with increased sympathetic activity. Thus the activity of the sympathetic nervous system appears to be inversely related to energy stores. The levels of hormones such as insulin, adrenal steroids, gonadal steroids and growth hormone play an important role in modulating nutrient intake and storage. The data seem to fit the hypothesis that nutrient stores are regulated systems with afferent feedback systems acting on a central controller which regulates intake, storage and metabolism of nutrients through modulation of the autonomic nervous system and motor control of food seeking. PMID- 3326851 TI - Protein and amino acids in the regulation of quantitative and qualitative aspects of food intake. PMID- 3326852 TI - Professor Augusto Corradetti 1907-1986. PMID- 3326853 TI - Centenary biographical note. David Keilin 1887-1963. PMID- 3326854 TI - Solid-phase peptide synthesis: a silver anniversary report. AB - It has been a quarter of a century since Merrifield's initial report on solid phase peptide synthesis. The field has matured significantly in recent years with a better understanding of the underlying chemistry. This is reflected by new, milder orthogonal protection schemes and more efficient coupling methods, some of which have been incorporated into automated systems. Advances in purification, especially high performance liquid chromatography, have had a major impact. The efficacy of these improvements has been demonstrated by an impressive litany of applications to biological problems. PMID- 3326855 TI - Psychiatric training for primary care residents: proposed standards. AB - Most of the nation's psychiatric care is provided by primary care physicians, and this trend is expected to continue. Primary care physicians see themselves as poorly trained in psychiatry, and evidence supports a high incidence of missed diagnosis and inadequate or inappropriate treatment. In addition, poor training may underlie the indifference to psychiatric problems often demonstrated by primary physicians. The Ohio Psychiatric Association Foundation has designated an annual award to be given to the primary care program which provides the best psychiatric training in the state, and the psychiatric training directors met to develop criteria for selecting the recipients. The resulting standards emphasize the importance of training which is relevant to a medical care setting, provided by psychiatrists, and supportive of the integration of psychiatric methods into medical care. PMID- 3326856 TI - Masked depression: its interrelations with somatization, hypochondriasis and conversion. AB - Masked depression appears to be a common clinical phenomenon. Most depressions present with some somatic complaints in addition to affective and cognitive ones. About one half of all depressions seen by primary care physicians initially present predominantly or exclusively with somatic symptoms. Many of these depressions are not recognized or are misdiagnosed and mistreated. The possible reasons for this are discussed here. The phenomenon of somatization in depressions and other conditions is reviewed and the interface with other related clinical problems like hypochondriasis and conversion is delineated. It is hypothesized that the proportion of depressions that are masked is positively correlated to the patients' tendency to somatize and negatively correlated to the doctors' ability to recognize depressions that hide behind somatic complaints. Suggestions for the diagnosis and treatment of masked depressions are given. PMID- 3326857 TI - Percutaneous and extracorporeal management of urolithiasis. PMID- 3326858 TI - One hundred twelfth critical bibliography of the history of science and its cultural influences. PMID- 3326860 TI - Quinidine-induced lupus erythematosus-like syndrome: three case reports and a review of the literature. AB - Three patients with an LE-like syndrome secondary to quinidine are described. Twenty-two similar cases are reviewed. The clinical picture is characterized mainly by polyarthritis, pleuritis, fever and dermatitis. The common laboratory findings are positive antinuclear antibodies, absence of anti-DNA antibodies, thrombocytopenia, leukopenia and abnormal liver function tests. This LE-like syndrome may appear within days or up to several years after the start of quinidine treatment and disappears completely a few weeks after discontinuation of the drug. PMID- 3326859 TI - Relationship between plasma renin activity and distal nephron sodium delivery and reabsorption in man. AB - The relationship between plasma renin activity and distal tubular sodium delivery and reabsorption was examined in man. Distal sodium delivery and reabsorption were measured during hypotonic volume expansion by the free water clearance method, or during hydropenia or isotonic volume expansion by the lithium clearance method. The maximal water diuresis method and the lithium clearance method both showed a negative correlation between plasma renin activity and distal sodium delivery and reabsorption. Only with the lithium clearance method, however, was it possible to measure plasma renin activity, distal sodium delivery and reabsorption in hydropenia without disturbances of water and electrolyte balance and plasma renin activity level. In hydropenia the plasma renin activity was higher and the fractional distal sodium delivery and reabsorption lower than during volume expansion. Our results support the idea that sodium chloride reabsorption at the macula densa region is negatively correlated to the plasma renin activity in man. PMID- 3326861 TI - Severe cholestatic jaundice due to sulpiride. PMID- 3326864 TI - L-forms: evolution or revolution? PMID- 3326862 TI - Localization of a multi-catalytic, high-molecular mass proteinase in the nuclei of muscle cells. AB - A multi-catalytic protease in muscle cells was uniquely localized to the nucleus of muscle cells, both in cell culture and in sections of muscle tissue. Although no specific substructure of the nucleus could be identified as the site of the enzyme by immunocytochemical techniques, the enzyme was nevertheless present in all muscle cell nuclei. It appears that MCP is a useful marker for nuclei found specifically in muscle tissue. PMID- 3326865 TI - The combined effect of sub-optimal temperature and sub-optimal pH on growth and toxin formation from spores of Clostridium botulinum. AB - Low-acid foods (pH greater than or equal to 4.5) are not sufficiently acidic to prevent growth of Clostridium botulinum in otherwise optimal conditions. The combination of sub-optimal pH and sub-optimal temperature may, however, result in a very significant reduction in the risk of growth of this bacterium compared with the risk in optimal conditions. The combined effect of incubation temperatures of 12 degrees and 16 degrees C and pH values between 5.2 and 5.5 on growth and toxin production from spores of Cl. botulinum during incubation for 28 d has been investigated. Growth and formation of toxin (type B) were detected only in medium at pH 5.5 and incubated at 16 degrees C, corresponding to a probability of growth from a single spore within 14 d of 1.6 x 10(-5). The probability of growth in 28 d in the remaining conditions was less than 9 x 10( 6). After transfer of inoculated media from 12 degrees to 30 degrees C growth occurred at pH 5.2-5.5 within 19 d. After transfer of inoculated media from 12 degrees to 20 degrees C growth occurred at pH 5.5 and 5.4 but not at pH 5.3 or 5.2 in 40 d. Growth at pH 5.2-5.5 was accompanied by formation of toxin, in most cases of types A or B. In addition to the effect of sub-optimal temperature and pH, chelation of divalent metal ions by citrate may have contributed to inhibition. PMID- 3326863 TI - In situ hybridization: alkaline phosphatase visualization of biotinylated probes in cryostat and paraffin sections. AB - Alkaline phosphatase immunochemical systems were evaluated for use in the demonstration of in situ hybridized biotin-labelled probes in frozen and fixed sections of tonsil. Three probes were used: total genomic DNA, pHY2.1, a human repetitive sequence which hybridizes to a 2.12 KB sequence on the Y chromosome (2000 repeats) and a 2.0 KB sequence on the autosomes (100-200 repeats), and human papilloma virus type II. Indirect, three- and five-stage detection methods were compared on cryostat sections. The indirect method involved the application of a streptavidin, biotinylated alkaline phosphatase sequence. The three-stage procedure comprised a mouse monoclonal anti-biotin, rabbit anti-(mouse immunoglobulin), mouse APAAP system. In the five-stage method the indirect and three-stage reagents were sequentially applied. Alkaline phosphatase was demonstrated using a Fast Red naphthol-capture method. The total genomic DNA probe was used initially to investigate hybridization conditions including the optimum temperature of denaturation, which was found to be higher than previously reported. The five-stage detection method gave the most sensitive results for the Y sequence probe, with intense demonstration of the Y body in male nuclei and autosomal sequences in female nuclei. This method was then applied to fixed tissue sections and gave Y body signals on Bouin's and Carnoy's fixed tissue. On the other hand tissue fixed using formalin-based solutions required proteolytic digestion as a pretreatment to hybridization for a Y body signal. The application of this methodology to viral diagnosis in routine fixed anogenital tissue and cytological preparations was also demonstrated. PMID- 3326866 TI - Antibody response to bacterial antigens covalently bound to biodegradable polymerized serum albumin beads. AB - Model vaccines have been made by covalently linking Clostridium botulinum type D toxin and Klebsiella pneumoniae capsular polysaccharide antigen to polymerized rabbit serum albumin beads. When injected into rabbits these bead vaccines induced an enhanced production of specific humoral antibody without causing adverse reactions. The adjuvant effect is due to a slow release from the bead structure and offers an alternative to oil emulsions and mineral salt adsorbents. PMID- 3326867 TI - Effect of the method of preparation of bacille Calmette-Guerin (BCG) vaccine on the properties of four daughter strains. AB - Samples of Bacille Calmette-Guerin (BCG) vaccines from four collaborating production laboratories, each of which had prepared vaccine from four different daughter strains of BCG, had previously been monitored for changes in colony morphology and the present study was undertaken to determine whether the changes observed were reflected in the patterns of protein secretion and lipid content. In the samples examined there was evidence for a correlation between colony morphology and the presence or absence of mycoside B. As the components of BCG that determine virulence and protective immunity are unknown, care must be taken to ensure constancy of the strains during the manufacture of vaccines. PMID- 3326868 TI - Human toxocariasis. PMID- 3326869 TI - Bacterial mutagenicity and the 4-quinolones. PMID- 3326870 TI - Antimicrobial drugs in human cardiac valves and endocarditic lesions. PMID- 3326871 TI - Origin and evolution of genes specifying resistance to macrolide, lincosamide and streptogramin antibiotics: data and hypotheses. AB - Resistance to macrolide, lincosamide and streptogramin antibiotics is due to alteration of the target site or detoxification of the antibiotic. Postranscriptional methylation of 23S ribosomal rRNA confers resistance to macrolide (M), lincosamide (L) and streptogramin (S) B-type antibiotics, the so called MLSB phenotype. Several classes of rRNA methylases conferring resistance to MLSB antibiotics have been characterized in Gram-positive cocci, in Bacillus spp, and in strains of actinomycetes producing erythromycin. The enzymes catalyze N6-dimethylation of an adenine residue situated in a highly conserved region of prokaryotic 23S rRNA. In this review, we compare the amino acid sequences of the rRNA methylases and analyze the codon usage in the corresponding erm (erythromycin resistance methylase) genes. The homology detected at the protein level is consistent with the notion that an ancestor of the erm genes was implicated in erythromycin resistance in a producing strain. However, the rRNA methylases of producers and non-producers present substantial sequence diversity. In Gram-positive bacteria the preferential codon usage in the erm genes reflects the guanosine plus cytosine content of the chromosome of the host. These observations suggest that the presence of erm genes in these micro-organisms is ancient. By contrast, it would appear that enterobacteria have acquired only recently an rRNA methylase gene of the ermB class from a Gram-positive coccus since the genes isolated in Escherichia coli and in Gram-positive cocci are highly homologous (homology greater than 98%) and present a codon usage typical of the latter micro-organisms. As opposed to the MLSB phenotype which results from a single biochemical mechanism, inactivation of structurally related antibiotics of the MLS group involves synthesis of various other enzymes. In enterobacteria, resistance to erythromycin and oleandomycin is due to production of erythromycin esterases which hydrolyze the lactone ring of the 14-membered macrolides. We recently reported the nucleotide sequence of ereA and ereB (erythromycin resistance esterase) genes which encode erythromycin esterases type I and II, respectively. The amino acid sequences of the two isozymes do not exhibit statistically significant homology. Analysis of codon usage in both genes suggests that esterase type I is indigenous to E. coli, whereas the type II enzyme was acquired by E. coli from a phylogenetically remote micro-organism. Inactivation of lincosamides, first reported in staphylococci and lactobacilli of animal origin, was also recently detected in Gram-positive cocci isolated from humans.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3326872 TI - AAC(1): a new aminoglycoside-acetylating enzyme modifying the Cl aminogroup of apramycin. AB - An aminoglycoside-acetylating enzyme produced by a strain of Escherichia coli with an unusual resistance phenotype was characterized. This enzyme was found to mono-acetylate apramycin, butirosin, lividomycin and paromomycin and diacetylate ribostamycin and neomycin to give reaction products which were distinguishable by HPLC analysis from those of AAC(2'), AAC(3) and AAC(6') enzymes. The enzyme, however, was not found to acetylate amikacin, fortimicin, geneticin, gentamicin, kanamycin A, netilmicin or tobramycin. The reaction product from the action of this enzyme on apramycin was purified and identified by nuclear magnetic resonance studies as 1-N-acetyl apramycin. The second site at which ribostamycin and neomycin B were modified by this enzyme was not determined but is postulated as the 6'-amino group. It is proposed that this enzyme be named AAC(1). PMID- 3326873 TI - Effect of ceftriaxone-induced alterations of bacteria on neutrophil bactericidal function. AB - Two bacterial strains (Staphylococcus aureus and Klebsiella pneumoniae) were exposed to subinhibitory concentrations of ceftriaxone. After an overnight culture in presence of 1 MIC of ceftriaxone either in broth or on solid medium S. aureus showed enlarged forms which were better phagocytosed (increase about 40%) and killed (increase about 50%) than control staphylococci. Exposure of K. pneumoniae to 0.1 MIC ceftriaxone resulted in filamentation of bacteria. When grown in the presence of 0.01 MIC, K. pneumoniae did not elongate into filaments but were significantly more phagocytosed (increase about 40%) or killed (increase about 170%) than control bacilli. The mechanism of the greater sensitivity to PMN killing of the altered S. aureus and K. pneumoniae was assessed either with phenylbutazone-treated PMN or by in-vitro exposure to crude granule extracts of PMN. The altered bacteria displayed a significant susceptibility to the non oxidative killing mechanism while untreated bacteria were unaffected by the non oxidative system. These data could explain the synergy observed between ceftriaxone and leucocytes in the killing of some micro-organisms. PMID- 3326875 TI - Novel beta-lactamase in a clinical isolate of Klebsiella pneumoniae conferring unusual resistance to beta-lactam antibiotics. PMID- 3326874 TI - Intranasal chalcone, Ro 09-0410, as prophylaxis against rhinovirus infection in human volunteers. AB - The antirhinovirus agent chalcone Ro 09-0410 was tested in double-blind place controlled volunteer trials for its protective efficacy against experimental rhinovirus infection. Fifty volunteers received either drug (26 volunteers) or placebo (24 volunteers) both before and after challenge with 20-40 tissue culture infecting dose (TCID50) of human rhinovirus 2 (RV2). There was no evidence that medication significantly reduced the incidence of infection or illness, indeed there was some increase in the nasal secretion produced. PMID- 3326876 TI - Identification of cardiac rejection with magnetic resonance imaging in heterotopic heart transplantation model. AB - It is important to evaluate the severity and extent of cardiac rejection in heart transplantations. Eight heterotopic heart transplantations using mongrel dogs were performed, and grated magnetic resonance imaging (MRI) of the donor hearts was carried out. High signal intensity was obtained in the rejected myocardium at the time of cardiac rejection, especially from the right ventricular wall to the intraventricular septal wall compared with the left ventricular posterolateral wall. In addition, MRI was performed in the excised heart. High signal intensity was also observed in the same region of the excised donor hearts. The histopathological rejection scores were well in agreement with prolonged T1 and T2 relaxation times; severe and mild rejection of the myocardium were distinguished by the T1 and T2 relaxation times. Our results suggest that MRI is able to visualize the transplanted myocardium undergoing rejection and that the right ventricular wall is more sensitive to cardiac rejection than the left. MRI may allow noninvasive evaluation of the severity and extent of cardiac rejection. PMID- 3326877 TI - Cardiac transplantation in dogs: evaluation with gated MRI and Gd-DTPA contrast enhancement. AB - It is important to evaluate the severity and extent of cardiac rejection in heart transplantation. Six heterotopic heart transplantation models in the peritoneal cavity were prepared with 12 adult mongrel dogs and in vivo imaging of the donor heart was performed using gated magnetic resonance imaging, (MRI) and Gd-DTPA contrast enhancement. In cardiac rejection, high signal intensity was obtained in the rejected myocardium, especially from the right ventricular wall to the intraventricular septal wall. The rejected myocardium was clearly visualized after administration of Gd-DTPA (0.5 mmol/kg body weight) via the femoral vein in all donor hearts. The mean ratios of signal intensity calculated from the rejected and normal myocardium were also increased from 25% to 42% after administration of Gd-DTPA. On the other hand, in the cases with no rejection, whole myocardium was visualized homogeneously before and after Gd-DTPA and there was no high signal intensity. Thus, our method has the potential of assessing the extent and severity of cardiac rejection using gated MRI and Gd-DTPA contrast enhancement. PMID- 3326878 TI - Outcome measurement in stroke rehabilitation research. AB - The use of outcome measures in stroke rehabilitation research is examined in a sample of 50 representative articles. Research studies are found not adequately to reflect the aims of stroke rehabilitation expressed by leading practitioners in the field. In particular, evaluations of rehabilitation programmes tend to use physical and self-care measures to the exclusion of broader aims. Recent advances in health measurement are reviewed, and it is recommended that researchers in this area make greater use of measures of subjective evaluations of health status, family involvement in rehabilitation, patient satisfaction, and quality of life. PMID- 3326879 TI - Transfer of vascularized grafts of iliac bone to the extremities. AB - We treated sixteen patients, all of whom had a large segmental defect of bone in an extremity, with transfer of a vascularized graft of the iliac crest. Thirteen patients had an open defect that required an osteomuscular or osteocutaneous graft; the other three had a closed segmental osseous defect and the graft of the iliac crest was transferred without soft tissue. The average length of the osseous defect was seven centimeters. For the defects of the lower extremity, the average time to osseous union was 8.8 months. For the defects of the upper extremity, it was four months. Three patients had delayed union due to difficulty in positioning the graft on the tibia and maintaining circulation to the overlying skin; this led us to modify our method of transfer. In six patients, we used an osteomuscular graft and a separate skin graft instead of the osteocutaneous flap. When performing the transfers to the tibia, we tried to place the graft in the coronal plane against the fibula for better alignment and stability. For the transfers to the distal part of the forearm, we did a double microvascular anastomosis. PMID- 3326880 TI - Dermatitis due to orthopaedic implants. A review of the literature and report of three cases. AB - The cases of three patients who had dermatosis that was caused by an orthopaedic implant are reported. The main clinical pattern was localized or generalized eczema or urticaria. The diagnostic criteria that have been proposed by various authors are reviewed. Removal of the implant did not always result in rapid disappearance of the dermatosis, presumably because a few particles of metal remained in the area of the implant. PMID- 3326881 TI - Biological fixation of porous-coated implants. PMID- 3326884 TI - Beta-blockers and cardioprotection--is there any good news from the recent trials? PMID- 3326882 TI - Pro-opiomelanocortin gene: a model for negative regulation of transcription by glucocorticoids. AB - The gene encoding pro-opiomelanocortin (POMC) offers an interesting model system to study negative control of transcription in eucaryotes. Indeed, glucocorticoid hormones specifically inhibit transcription of the POMC gene in the anterior pituitary. The POMC gene is predominantly expressed in the anterior and intermediate lobes of the pituitary. However, only anterior pituitary POMC transcription is inhibited by glucocorticoids and stimulated by corticotropin releasing hormone (CRH). Rat POMC promoter sequences required for anterior pituitary-specific expression were localized between positions -480 and -34 base pairs (bp) by DNA-mediated gene transfer into the POMC-expressing tumor cells. AtT-20. These POMC promoter sequences also confer glucocorticoid inhibition of transcription. While two of the six in vitro binding sites for purified glucocorticoid receptor identified in the rat POMC gene are within these sequences, only one is required for glucocorticoid inhibition; this binding site is located at position -63 bp in the promoter and overlaps a putative CCAAT box sequence. The DNA sequence of the POMC -63 bp receptor binding site is homologous to receptor binding sites identified in the glucocorticoid responsive element (GRE) of glucocorticoid-inducible genes. However, DNA sequence divergencies between these sites, in particular within the conserved hexanucleotide sequence 5'-TGTYCT-3', may be involved in their opposite transcriptional activity. Alternatively, binding of the receptor in the promoter proximal region of the POMC gene may inhibit transcription by a hormone-dependent repressor mechanism. PMID- 3326883 TI - Human teratocarcinoma stem cells: glycolipid antigen expression and modulation during differentiation. AB - Teratocarcinomas are germ cell tumors in which pluripotent stem cells, embryonal carcinoma (EC) cells, undergo differentiation along the pathways resembling those occurring during early embryogenesis. Human EC cell lines established in vitro provide a model for studying embryonic cellular differentiation in a way that is pertinent to early human development. The predominant glycolipid antigens expressed by EC cells of both humans and mice have globoseries core structures; in humans they are terminally modified to yield the monoclonal antibody-defined stage-specific embryonic antigens SSEA-3 and SSEA-4, and also globo-ABH antigens; in the mouse terminal modification yields the Forssman antigen rather than SSEA-3 and -4. These observations focus attention on the possible role of the P-blood group system, which regulates synthesis of globoseries oligosaccharides, in the behavior of cells in the early embryo and in teratocarcinomas. Marked changes in the core structures of the cell surface glycolipids occur as the EC cells differentiate; thus globoseries structures rapidly diminish and are replaced by lactoseries and then by ganglioseries glycolipids. During differentiation of the NTERA-2 line of pluripotent human EC cells into neurons and other cell types, the various subsets of differentiated cells that arise are distinguished by their differential expression of new glycolipid antigens, particularly ganglioside GT3 (recognized by antibody A2B5), and ganglioside 9-0-acetyl GD3 (recognized by antibody ME311). Neurons are found among the A2B5+/ME311- cells. PMID- 3326885 TI - Therapeutic progress--review. XXIX. Is there a role for low-dose angiotensin converting enzyme inhibitors in the treatment of mild to moderate hypertension? PMID- 3326887 TI - The pharmaceutical industry in the U.S.S.R. PMID- 3326886 TI - A comparative study of the microbial antiadherence capacities of three antimicrobial agents. AB - The antimicrobioal agents, taurolidine, chlorhexidine and povidone-iodine were examined for microbial anti-adherence activity. Two adherence systems were investigated using light microscopic and radio-isotopic assay methods: that of an oral isolate of Candida albicans to human buccal epithelial cells and of a urine isolate of Escherichia coli to human uroepithelial cells. Each of the three agents exhibited significant anti-adherence activity which was concentration dependent. The activity was expressed at subminimum inhibitory concentrations of the agents. Treatment of either the microbial or epithelial cells resulted in significant reductions in adhering micro-organisms. Consideration of the data in respect of the skewness coefficient and percentage clear epithelial cells indicated that the agents exhibited a broadly based anti-adherence capacity. PMID- 3326888 TI - The stability of carboplatin in ambulatory continuous infusion regimes. AB - Several anti-cancer agents are administered by continuous infusion in an attempt to improve the therapeutic index obtained with solid tumours. In Exeter this approach, combined with the use of ambulatory infusion pumps, forms the basis of a home oncology programme in which a complete course of medication in pre-filled syringes is supplied on an out-patient basis. It is essential to ensure that the drug remains stable during storage prior to use and also during infusion where the temperature of the drug solution in a holster-worn ambulatory pump can reach 37 degrees C. In this study the stability of a carboplatin infusion (20 mg in 2 ml) in pre-filled syringes under storage and in-use conditions was determined using a stability-indicating HPLC assay. There was no loss of carboplatin from pre-filled syringes stored at 4 degrees C for 5 days. At 37 degrees C, the loss of carboplatin was 3.1% over 24 h. PMID- 3326889 TI - Development of cardiac sympathetic and adrenal-medullary responses in borderline hypertensive rats. AB - Borderline hypertensive (BHR) rats are the first generation offspring of a cross of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats. In adulthood, BHRs have systolic blood pressures in the 140-160 mm Hg range. If subjected to chronic stress paradigms, however, BHRs develop sustained and permanent elevations in systolic blood pressure (180-200 mm Hg). In the present study, we examined the functional development of cardiac and adrenal medullary responses to reflex activation of the sympathetic nervous system in preweanling BHR and WKY rats. Pups of the two groups were injected with insulin or saline at 4, 8, 12, or 16 days of age and sacrificed 3 h later. Insulin produces an acute lowering of blood glucose which is attended by a centrally mediated increase in sympathetic activity. The induction of ornithine decarboxylase (ODC) activity in heart and the depletion of epinephrine from the adrenal medulla were biochemical indicators of functional sympathetic neurotransmission. WKY and BHR pups had similar levels of cardiac ODC activity under basal conditions and following administration of insulin. In contrast, BHRs had higher amounts of adrenal norepinephrine and epinephrine from 4 to 16 days of age and greater depletion of adrenal epinephrine following insulin administration at 8, 12 and 16 days of age. These findings indicate that BHRs have a greater capacity for catecholamine biosynthesis, storage and release in the adrenal medulla during the preweanling period compared to age-matched normotensive WKY controls. This alteration in the adrenal medulla during the preweanling period may contribute to the susceptibility of adult BHR rats to stress-induced hypertension. PMID- 3326890 TI - In vivo insulin antagonism but evanescent in vitro tissue effect in rats with growth hormone-secreting tumors. AB - Rats bearing mammosomatotropic tumors have raised insulin but lowered glucose concentrations. To determine if growth hormone (GH) secreted by these tumors causes insulin antagonism, pancreatic suppression tests utilizing infusions (per kg per min) of glucose (8 mg), insulin (200 ng) and somatostatin (1.4 micrograms) for 130 min were performed. Although the steady state plasma glucose and insulin levels (mean of 90, 100, 110, 120 and 130 min samples) were similar in 8 control and 13 tumor-bearing rats, the decrease from the already depressed basal glucose concentration (mmoles/l +/- SE) in the tumor animals was less than in the controls (0.90 +/- 0.30 vs. 2.56 +/- 0.040, p less than 0.005). Since the interpretation of these results was not entirely clear, glucose and insulin glucose tolerance tests were performed. The glucose disappearance rates (%/min +/ SE) in the glucose tolerance test were lower in 17 tumor rats (2.00 +/- 0.13) compared to 17 control animals (2.51 +/- 0.22). This difference just missed statistical significance (t = 2.00, value of 2.04 necessary for p = 0.05). The decrease occurred in the presence of increased insulin (nmoles/l X 16 min) levels (4.29 +/- 0.38 vs. 2.58 +/- 0.29, p less than 0.005) suggesting insulin antagonism. The glucose disappearance rates (%/min +/- SE) in the insulin-glucose tolerance test were less in 12 tumor-bearing rats compared to 11 control animals (2.80 +/- 0.29 vs. 4.12 +/- 0.35, p less than 0.02). Thus, these GH-secreting tumors cause insulin antagonism in vivo. Freshly isolated hepatocytes from these tumor-bearing animals manifest decreased insulin binding and action (Diabetologia 25:60, 1983). In the present study, however, insulin binding and action (net glucose-C14 incorporation into glycogen) were normal after the hepatocytes were cultured for two days. This suggests that the changes induced by GH in vivo that lead to insulin antagonism are short-lived. PMID- 3326891 TI - Insulin as a factor of increased androgen production in women with obesity and polycystic ovaries. AB - To evaluate the possible role of moderate hyperinsulinemia on abnormal androgen secretion, we examined 4 age and weight-matched groups of obese subjects: 2 groups of women with normal menses whose fasting insulin (IRI) levels were less than or equal to 20 microU/ml (OB-I) or greater than or equal to 40 microU/ml (OB I) and 2 groups of women with polycystic ovaries who were similarly grouped. All subjects underwent an oral glucose tolerance test, blood sex hormone determination and multiple LH determinations. Compared to OB, OB-PCO women showed significantly higher values of LH, androgen and estrogen concentrations. OB-I and OB-II showed similar hormonal patterns. On the contrary, OB-PCO-II presented significantly (p less than 0.05) higher androstenedione concentrations (348.7 +/- 129.9 ng/dl) (m +/- SD) than OB-PCO-I women (237.0 +/- 73.7 ng/dl). These differences were evident despite similar plasma LH concentrations. In conclusion, these results suggest that insulin may be a factor amplifying LH-dependent androgen secretion in hyperandrogenized women with obesity and PCO. PMID- 3326892 TI - Isolated glucocorticoid deficiency. AB - A three-month-old boy with hypoglycemic episodes, feeding problems and hyperpigmentation is described. Hormone assays revealed elevated serum ACTH values and low levels of plasma cortisol that did not rise after exogenous ACTH administration; blood pressure, serum electrolytes and earlier plasma aldosterone and renin activity were in the normal range. These data suggest a diagnosis of an isolated glucocorticoid deficiency, secondary to unresponsiveness to ACTH. Replacement therapy with glucocorticoids was highly effective. Despite replacement therapy, during follow-up he had an increase in basal plasma renin activity with aldosterone concentration normal. In our patient, a mineralcorticoid deficiency might eventually develop; therefore, the selective glucocorticoid deficiency might also be part of a progressive defect involving the glomerulosa too. PMID- 3326895 TI - [Continent enterocystoplasty for diversion and replacement in adults]. PMID- 3326893 TI - Factitious hyperinsulinemic hypoglycemia: confirmation of the diagnosis by a species-specific insulin radioimmunoassay. AB - Surreptitious self-administration of insulin is an important cause of hypoglycemia. A 28-year-old female hospital ward clerk presented with hypoglycemia associated with an elevated plasma insulin level and a low plasma C peptide concentration. Factitious illness was denied by the patient until it was definitively proven by using a species-specific insulin radioimmunoassay that the type of insulin circulating at the time of hypoglycemia was of animal rather than of human origin. The differential diagnosis of hypoglycemia associated with hyperinsulinemia and the current laboratory methods which may be employed to distinguish between factitious hypoglycemia and endogenous hyperinsulinism are discussed. PMID- 3326896 TI - [Renal failure caused by renal artery stenosis: effects of revascularization]. AB - From 1972 to 1986, 22 patients underwent surgical treatment for severe renovascular hypertension and rapidly progressive renal failure caused by atherosclerotic disease of the renal artery or dysplasia (group A), or by post transplant renal artery stenosis (group B). 1. Group A (n = 16): These patients were assessed preoperatively with the measurement of serum creatinine and blood urea levels (means 271 +/- 204 mumol/l and 15.6 +/- 10.3 mmol/l respectively) and renal clearances. 5 patients underwent aorto-renal bypass (bilateral in one case) and 11 patients were treated by autotransplantation of the kidney. Operative mortality was 6.2%. Improvement in renal function was statistically significant at 1 and 6 months postoperatively (p less than 0.05). After a mean follow-up of 31 +/- 12 months, renal function was normal in 8 patients, improved in 4, unchanged in 1 and worse in 2. At short and long-term, 81% of the patients were normotensive without medication of with an improved blood pressure (p less than 0.001). 2. Group B (n = 6): Transplant revascularisation was performed on average 10 +/- 8 months after renal transplantation. 5 patients had renal function impairment (mean serum creatinine 241 +/- 96 mumol/l, mean blood-urea 16 +/- 17 mumol/l) and 1 patient a posttransplant anuria. Resection of anastomotic (n = 2) or post-anastomotic (n = 4) lesions was carried out in all case with a new anastomosis (n = 2) or a "crossed" anastomosis (n = 4). On the 24th hour one patient underwent a second revascularization because of immediate postoperative anuria secondary to another anastomotic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3326897 TI - [Contusion on horseshoe kidney. Apropos of 2 cases]. AB - Based on the personal observation of two cases and a series of 40 patients reported in the literature, the specific problems related to injuries to horseshoe kidney are evoked. The first case involved crushing of the isthmus against the spine recognized at operation on the 5th day and suggested by urography, CT scan and arteriography data. Abstention from surgery in the second case was decided on initial urography and ultrasound findings and the rapid, spontaneously favorable course. A literature review failed to provide much original data related to the anatomical anomaly, too frequently detected during emergency surgery. The only particularity is related to rupture of isthmus which may damage upper excretory pathways; this explains the interest for the authors of pyelostomy in case of conservative surgery in this context. When surgery is indicated this should be reserved to severe forms and postponed. It is important to carry out arteriography in addition to urography and a CT scan because of the particularity of the vascularization of this type of kidney: the anterior transperitoneal approach appears to be the best adapted. PMID- 3326894 TI - Circulating thyroid hormone autoantibodies. PMID- 3326898 TI - [Natural history of cancer of the prostate]. AB - Based on a literature review, the natural history of cancer of prostate is analyzed stage by stage. Included in the study were only untreated patients or those in whom treatment had not affected the course of this neoplasm. Clinico pathologic correlations, conversion rate of localized to metastatic forms and 5 and 10 year survival rates were determined for each stage. For stage A (25%) the criteria of size and tumoral grade should be analyzed relative to their incidence on the neoplastic course and patient survival rate. The problem of stage A1 prostate cancer in a young patient is analyzed. For stage B (25%) the determining factor for local extension and the presence of metastatic pelvic glands is the grade. Emphasis in stage C (20%) is placed on the importance of the distinction between penetration and extension through the capsule, on which the possible need for adjuvant radiotherapy is based. For stage D (30%) a more detailed analysis is made of the problems raised by elevated plasma acid phosphatases levels in the presence of a negative finding for extension of tumor and the significance of pelvic gland metastases. PMID- 3326899 TI - [Uretero-ileal anastomosis using the modified Leduc-Camey technic. Surgical technic]. AB - A modified Leduc-Camey technic for uretero-ileal anastomosis was used in 96 patients over a period of one year, complications related to this type of anastomosis, and requiring recovery surgery, being noted in 2 cases. When compared with more than 300 anastomoses performed using the original Leduc-Camey technic, this modified procedure using absorbable sutures appeared to be simple, effective and very rapid. It is a valid method for Camey type reconstruction bladders and also for Bricker type or Kock's pouch type continent diversion operations. PMID- 3326900 TI - [How to examine an non-contractile bladder]. AB - Bladder contractility is dependent on the quality of the detrusor muscle and its innervation, and acontractility can therefore result from muscular or neurologic dysfunction. Etiologic factors involved in this functional disorder include collagen overload of the bladder wall and/or denervation or inhibition phenomena. Cystometric conditions necessary and sufficient for recognition of the disorder are indicated, the stop-test being an indispensable exploration to establish diagnosis. The Lapides test is reliable when peripheral neurologic lesions are involved but the lesion must be complete; for incomplete lesions greater sensitivity is obtained with electrophysiologic tests such as analytic electromyography, sacral evoked potentials or rapid cystometry. Tests using an alpha-blocker allow recognition and lifting of reflex inhibition, particularly in neurologic patients with high level lesions. Proof of the psychogenic nature of the retention in hysterical patients is more difficult to obtain, and a specific test is not available, apart from histology, for diagnosis of bladder collagenosis. PMID- 3326901 TI - [Extension to the upper urinary tract of excreto-urinary carcinoma of the bladder. Apropos of 6 cases]. AB - Of a total of 261 patients with carcinoma of bladder, 6 (2.3%) presented secondary lesions in upper urinary tract 3 to 13 years after initial diagnosis, including one only after total cysto-prostatectomy. These 6 patients represent 12 renal units, including 5 with iatrogenic reflux, and all had secondary urethral localizations. Urine cytology was particularly reliable since results were positive after treatment of bladder lesion and before detection of upper urinary tract foci. The latter developed whatever the stage or grade of the bladder tumor, from carcinoma in situ, through grade I stage O (3 cases), to undifferentiated and infiltrating tumor. Treatment included surgical excision, endoscopic resection including upper urinary tract (2 cases) and radio-chemo and immuno-therapy (BCG). Results were only fair with 2 deaths and 4 survivors, all with recurrence, although one has not had surgery and is in comfort without dialysis after 18 years. Two hypotheses have been invoked for the origin of these secondary upper tract tumoral localizations: grafting of tumoral cells propulsed upwards by vesicorenal reflux, almost always iatrogenic and a mysterious carcinogenic factor in urine responsible for the multicentric origin of lesions. Both are probable in part, the former appearing well established statistically. These widespread lesions require the application of all urologic resources but treatment is deceiving: since no test exists to determine evolutive potential with accuracy, treatment of bladder cancer lies between the risk of doing too much or too little. PMID- 3326902 TI - Recombinant DNA technology and its application to leprosy research. PMID- 3326903 TI - Histiocytic lymphoma simulating lepromatous leprosy--a case report. AB - Histiocytic lymphomas are known to begin with skin lesions and remain localised to the skin for months or years before visceral involvement becomes evident. We report a case of nodular histiocytic lymphoma with clinical features simulating lepromatous leprosy. PMID- 3326904 TI - Mycobacterium leprae can penetrate nasal mucosa. PMID- 3326905 TI - On the "Culture medium for cultivation of M. leprae" published by Dr. Laszlo Kato. PMID- 3326906 TI - The recipients of IFCC's premier awards 1987. PMID- 3326908 TI - [Urinary enzymes in research and in clinical medicine. Report on a symposium of the Humboldt-Universitat Berlin and the Bezirkskrankenhaus Frankfurt/Oder in Frankfurt/Oder, 22-25 April 1987]. AB - The symposium was dedicated exclusively to the subject of urine enzymes. Thirty nine lectures were given, in which 58 participants from 10 countries presented and discussed our present state of knowledge in the field of urine enzyme diagnosis, covering all aspects from fundamental research to its clinical application. This report summarizes the essential points of interest that arose from the lectures and discussions. PMID- 3326907 TI - Inflammation and phagocytosis. Report on the workshop conference of the German and Austrian Societies for Clinical Chemistry and Immunology in Igls, Tirol, February 6-7, 1987. PMID- 3326909 TI - The use of scanning electron microscopy in the dating of human skeletal remains. PMID- 3326910 TI - Involvement of hippocampus in Creutzfeldt-Jakob disease. AB - The hippocampus is generally believed to be only rarely affected in Creutzfeldt Jakob disease. In a systematic study of the hippocampus in 6 cases of Creutzfeldt Jakob disease, the stratum moleculare-lacunosum showed a definite spongiform change with gliosis in 5 cases. The stratum radiatum et pyramidale showed spongiform change in 3 of the 5 cases. The subiculum, presubiculum, parasubiculum and entorhinal cortex were involved in all the cases. These results suggest that involvement of the hippocampus may not be uncommon in Creutzfeldt-Jakob disease. The stratum moleculare-lacunosum seems to be the site preferentially affected. This pathology may contribute to progression of dementia in Creutzfeldt-Jakob disease. PMID- 3326911 TI - Comparison of the effects of continuous subcutaneous infusion and split-mixed injection of insulin on nerve function in type I diabetes mellitus. AB - Comparable groups of type I diabetic patients (n = 19) were matched for age, duration of diabetes, mean HbA1 values, insulin requirements, degree of neuropathy, and the mean of nerve conduction velocities (CV) in median, ulnar, and peroneal motor and median, ulnar, and sural sensory nerves. One group (n = 9) was managed with continuous subcutaneous infusion of (regular) insulin (CSII); the other (n = 10) with split-mixed injections of (intermediate and regular) insulin (SMII). After 12 months, glucose regulation was equally and significantly improved in both groups (P less than 0.005), although it was not sufficiently intense to normalize mean total glycosylated hemoglobin values in either group. Furthermore treatment produced no difference between groups in the values for mean amplitude of glycemic excursions, 12 month average of consecutive M-values or in clinical evaluation. However, in the CSII group, mean CV had increased 6.4% (2.75 + 0.56 m/s; mean +/- SEM) versus 1.3% (0.57 +/- 0.54 m/s) in the SMII group (P less than 0.005). Multivariate analysis on a nerve-by-nerve basis found significantly improved conduction in 2/6 nerves (median motor; ulnar sensory) in the CSII group compared to the SMII group. These results suggest that CSII may provide a more favorable microenvironment for nerve repair. PMID- 3326912 TI - Spongiform encephalopathy with extensive involvement of white matter. AB - We report a proven case of CJD with prolonged clinical course and white matter involvement which consisted of severe, widespread myelin damage in the forebrain and cerebellum but with sparing of the internal capsule. Histologically, there was status spongiosus of the involved white matter with axonal loss, proliferation of hypertrophic astrocytes and scattered and perivascular foamy macrophages. White matter lesions have not been considered to be a significant feature of CJD. In the last few years, however, a few cases have been described with prominent degeneration of cerebral white matter. We believe that our findings corroborate the existence of an entity that at present may only be defined as spongiform panencephalopathy. PMID- 3326913 TI - MRI of spinal cord congenital malformations. Chiari malformations and dysraphism. PMID- 3326914 TI - Intracranial vascular sarcomas. A series of 12 cases and a review of the literature. PMID- 3326915 TI - Quality of life with antihypertensive medication. AB - Mild to moderate hypertension is often an asymptomatic disease, but it is strongly associated with increased risk of cardiovascular, renal and central nervous system morbidity and mortality. Because of the chronic nature of the disease, treatment involves the reduction of blood pressure without functional impairment. Since the adverse effects of pharmacological agents greatly reduce compliance, it is of prime importance not only to control blood pressure but also to preserve the patient's quality of life. Previous studies have demonstrated the adverse effects observed in patients treated with antihypertensive medications, but few have attempted to analyse the impact on the quality of life. Therefore, a multicentre trial was carried out to investigate the quality of life in hypertensive patients before and after treatment with the beta-adrenergic blocker propranolol or the calcium channel blocker nitrendipine. Both treatments were effective in the reduction of blood pressure. Preliminary results indicated that patients taking nitrendipine were more vigorous (P less than 0.01) and less fatigued (P less than 0.05) than those taking propranolol. In addition, patients in the propranolol group perceived a decrease in a partner's sexual satisfaction (P less than 0.05). No other major negative impacts on the quality of life were caused by either drug. These preliminary data indicate that nitrendipine and propranolol reduced blood pressure equally, but that nitrendipine caused less of a negative impact on the quality of life than propranolol. PMID- 3326916 TI - Age and antihypertensive response to calcium antagonists. AB - Calcium antagonists are being increasingly used for the treatment of hypertension. Analysis of response patterns shows that they are particularly effective in older, low-renin and black patients. Although the reasons for this pattern are not quite clear there is evidence that the attenuated cardiovascular reflex responses may be important in these groups. Baroreflex responses are blunted in older subjects and even more so in older hypertensive patients. Patients with low-renin hypertension also show impaired sympathetic nervous system response and black subjects often have low renin levels. A diminished counter-regulatory response to the vasodilating effects of calcium antagonists may partly explain the good clinical responses of older, low-renin and black patients. PMID- 3326917 TI - Calcium antagonists as antihypertensive agents are effective in all age groups. AB - Calcium antagonists have added a new dimension to the therapy of hypertension. They have proved to be versatile, effective drugs for the short- and long-term management of hypertension. Since these drugs have favourable effects on tissue blood flow, they offer the hope of providing tissue protection in hypertensive patients. Some investigators have claimed that the effectiveness of calcium antagonists in hypertension is age-dependent, older subjects showing a better response than younger individuals. However, a careful analysis reveals that calcium antagonists are effective in all age groups and the magnitude of response may be related to the level of pretreatment blood pressure. PMID- 3326918 TI - Calcium antagonists and responsiveness of the adrenal glands to aldosterone releasing stimuli in hypertensive patients. AB - This study was designed to determine whether a reduced responsiveness of adrenal zona glomerulosa to physiological stimuli could be responsible for the lack of a proportional rise in plasma renin activity and plasma aldosterone during administration of calcium antagonists. We selected 11 hypertensive patients and measured the rise in plasma aldosterone in response to infusions of angiotensin II or potassium chloride before and after a 7-day treatment with fully antihypertensive doses of nifedipine (20 mg twice a day), while the patients were kept on a constant daily intake of sodium (100 mmol) and potassium (40 mmol). The treatment with nifedipine induced a significant reduction in both systolic and diastolic blood pressures; the infusions of angiotensin II (0.150, 0.375 and 0.750 microgram/min, each rate for 30 min) and of potassium chloride (50 mmol in 500 ml of 5% glucose in 50 min) caused similar rises in plasma aldosterone before and during the administration of the calcium antagonist. Therefore, our results indicate that responsiveness of the adrenal zona glomerulosa to physiological stimuli is maintained despite blockade of calcium channels capable of significantly lowering arterial blood pressure. PMID- 3326919 TI - Calcium antagonists and diuretics as combined therapy. AB - Whether a diuretic confers an additional antihypertensive effect on patients receiving treatment with calcium channel blocking drugs remains controversial. The results of seven recently reported trials are summarized, with the conclusion that much of the confusion arises because of inadequacies in trial design, particularly the failure to take into account placebo responses and period effect, and the inclusion of too few subjects to give the trial sufficient power to demonstrate a significant fall in blood pressure. Further difficulties in comparing one trial with another include differences with respect to age, race, severity of hypertension and renin status in the patient populations under investigation, since all these factors may influence responsiveness to therapy with both classes of agent. Although there may be theoretical grounds for believing that, under circumstances of optimal calcium entry blockade in vascular smooth muscle, diuretics might not cause any further reduction in blood pressure, until such time as full dose-response relationships are established for each class of agent alone and in combination, the problem will remain unresolved. PMID- 3326920 TI - Captopril and nifedipine interactions in the treatment of essential hypertensives: a crossover study. AB - In order to evaluate the antihypertensive effect and the tolerability of combination therapy with an angiotensin converting enzyme inhibitor (captopril) and a dihydropyridine calcium antagonist (nifedipine) compared with monotherapy and placebo, we studied 32 uncomplicated essential hypertensives. At the end of a 1-month placebo washout period, their diastolic blood pressure was greater than 105 and less than 120 mmHg. The subjects then received, according to a double blind randomized crossover design, captopril (50 mg twice daily), nifedipine (20 mg twice daily), captopril plus nifedipine at the same doses and the corresponding placebo, each treatment being given for 1 month. Both captopril and nifedipine significantly reduced mean blood pressure, which was further and significantly reduced by the combination of the two drugs. The decreases in mean blood pressure induced by nifedipine were significantly greater than those induced by captopril, and those induced by the combined therapy were significantly greater than those induced by either drug on monotherapy. The heart rate was significantly increased only by nifedipine, and to a similar, but not significant, extent by the combination therapy. Plasma renin activity was similarly and significantly increased and urinary aldosterone tended to decrease to a similar extent under the three active treatments. Adverse effects were mild to moderate in intensity; their incidence under captopril was lower than that under placebo, while the incidence under nifedipine and combined therapy was greater than under placebo. Ankle oedema disappeared under the combined therapy in three out of four patients who developed this side effect under nifedipine, although one additional patient developed ankle oedema under combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3326921 TI - Cerebral blood flow and calcium antagonists in hypertension. AB - Antihypertensive treatment reduces the risk of ischaemic strokes and cerebral haemorrhage as complications of excessive or long-standing hypertension. However, neurological dysfunction and brain damage may also accompany acute and, under certain conditions, even chronic antihypertensive treatment. Treatment should therefore be instituted restrictively and cautiously, with special regard to the action of antihypertensive drugs on cerebral perfusion in patients with an increased risk for treatment-induced cerebral ischaemic complications, e.g. patients with hypertensive encephalopathy, patients with autonomic dysfunction or elderly patients with suspected sclerotic stenosis of cerebral or neck arteries. The present study is a review of the structural and functional lesions of cerebral vessels observed in acute and chronic hypertension, together with the effects of antihypertensive drugs on cerebral blood flow. Calcium channel blockers such as nifedipine, nitrendipine and verapamil may have advantages as first-line drugs in the treatment of patients with an elevated risk for cerebral hypoperfusion, because of their selective action on vasoconstricted vessels and their differential effects in different regional vascular beds. The particular efficacy of calcium antagonists in acute antihypertensive treatment, with a significant increase in cerebral blood flow in the case of nifedipine, and also in chronic antihypertensive therapy without decreasing cerebral blood flow, may change the traditional management of hypertensive emergencies, as well as of other patients at risk of treatment-induced complications. PMID- 3326922 TI - Effects of calcium antagonists on glucose homeostasis and serum lipids in non diabetic and diabetic subjects: a review. AB - Results from early in vitro experiments have led to the assumption that a deterioration in carbohydrate metabolism must be expected if diabetic patients are treated with calcium antagonists. In order to determine the truth of this assumption, we reviewed 74 publications reporting effects on glucose homeostasis from acute, short-term and long-term therapy with calcium antagonists in non diabetic patients, and 35 papers and abstracts dealing with the same problem in diabetic patients. The analogous question concerning the influence of calcium antagonists on the serum lipid profile was pursued in 43 recent communications. Long-term studies in particular suggest that although minor transitory changes under special circumstances cannot be excluded, in all likelihood neither glucose nor lipid homeostases are unfavourably altered by current clinical dosages of calcium antagonists in non-diabetic subjects or in patients with diabetes mellitus. Therefore, the benefit of antihypertensive or anti-anginal treatment with these medications is not compromised by untoward metabolic cardiovascular risks. PMID- 3326923 TI - Preceptors and stewardship--our heritage of excellence in pediatric surgery. PMID- 3326924 TI - Pyelonephritis following pediatric renal transplant: increased incidence with vesicoureteral reflux. AB - The association between pyelonephritis and vesicoureteral reflux (VUR) following pediatric renal transplantation is unclear. To understand the relationship of vesicoureteral reflux with urinary tract infection (UTI) and pyelonephritis, 67 patients were evaluated for reflux and pyelonephritis. Sixty-seven pediatric patients, aged 2 to 18 (39 males and 28 females) underwent renal transplantation. Beginning in 1982, all patients underwent voiding cystourethrography or radionuclide voiding studies 1 to 3 months postoperatively to assess the incidence of VUR. Techniques of ureteroneocystostomy (UNC) included the Leadbetter-Politano (L-p) in 39 cases, and two different modifications of the LICH (herein called LICH-1 and LICH-2) in 30 cases. Urinary cultures were performed routinely. Pyelonephritis was considered present in any patient with UTI and increased serum creatinine or fever greater than 38.5. VUR occurred in 36% of patients; highest in LICH-1 (79%), intermediate in L-P (22%), and lowest in LICH-2 (9%). VUR was not statistically significantly higher in females (43%) v males (31%). UTI occurred in 37% of patients. The difference in incidence between females (54%) and males (26%) was significant (P less than .05). The frequency of UTI in patients with VUR was 46% v 33% in patients without reflux (NS). However, pyelonephritis that occurred in 16% of cases overall was present in 82% of UTIs in patients with reflux v 14% of UTIs in patient without reflux (P less than .01). Pyelonephritis is significantly increased in pediatric renal transplant patients with UTI was have VUR. A nonrefluxing UNC is advocated in all patients. All renal transplant patients should have routine monitoring of urinary cultures and should be evaluated of VUR posttransplant. PMID- 3326925 TI - Blunt injury to the pancreas in children: selective management based on ultrasound. AB - Twenty-one children with blunt injuries to the pancreas were treated over a 5 year period. Group I consisted of 12 patients brought to our hospital within 24 hours of injury. Group II included nine patients who were referred to us more than 24 hours after injury following initial treatment at another hospital. Two group I patients died within four hours of admission from other causes. Three had early laparotomy for other injuries. Of these, two had a contusion and one had a complete transection of the pancreas. All recovered uneventfully after appropriate surgical treatment. The remaining seven were all treated nonoperatively. Two had obstructive pancreatitis secondary to duodenal hematomas, three had pancreatic contusions, and two developed pancreatic pseudocysts. All seven recovered completely without operation. In group II, three patients had undergone laparotomy elsewhere. All three had pancreatic contusions. However, only one had appropriate drainage of the injured pancreas; he recovered uneventfully. Two, who were not drained, developed pseudocysts and one of these required surgical drainage by cystgastrostomy. The other six patients in group II presented to our hospital with established pseudocysts. Three of these resolved with nonoperative treatment but three required drainage. Overall, six of ten posttraumatic pancreatic pseudocysts resolved without surgical treatment. The single most useful diagnostic test in the management of these patients was abdominal ultrasound (US). US revealed specific anatomic lesions of the pancreas- contusion, obstructive pancreatitis, or pseudocyst--and provided an objective guide to management. Surgical intervention is not necessary in all cases of pancreatic trauma. PMID- 3326927 TI - Reversal of ischemic liver failure by intrasplenic liver cell transplantation. AB - A model of ischemic hepatic failure in Sprague-Dawley rats (SD) with 100% mortality has been developed by one-hour occlusion of the right portal vein and hepatic artery followed by left 70% hepatectomy. The intrasplenic injection of 40 x 10(6) syngeneic adult or three-day neonatal single liver cell suspensions decreased the mortality from 100% to 50% and 36%, respectively. Mortality decreased with increasing time from the intrasplenic injection of neonatal liver cells to the time of acute hepatic ischemia. Mortality also decreased with increasing interval between hepatic ischemia and removal of the transplanted liver cells by splenectomy. Intrasplenic injection of graded doses of neonatal liver cells decreased mortality from 75% at a dose of 10 x 10(6) cells, to 36% at 160 x 10(6) cells. Treatment of neonatal liver cells with metabolic inhibitors did not significantly affect their ability to reverse acute hepatic ischemia. PMID- 3326926 TI - Why luteinizing-hormone-releasing-hormone nasal spray will not replace orchiopexy in the treatment of boys with undescended testes. AB - Two courses of LHRH nasal spray (400 micrograms three times a day for 28 days), partly administered in a double-blind placebo-controlled study, resulted in the descent of 48 of 281 testes (18%) in 237 prepuberal boys. Logistic regression analysis confirmed the clinical observation that pretreatment testicular position was the major factor influencing treatment results: the lower the pretreatment testicular position, the better the result. Of the unsuccessfully treated boys, 170 with 196 undescended testes subsequently underwent orchiopexy revealing anatomic anomalies that accounted for failure of hormonal treatment in 80% of the cases. Most frequent finding amounted to an underdeveloped processus vaginalis, extending no further than the level of the pubic bone, often associated with major epididymal deformities and a lack of obliteration of the processus vaginalis (107 of 196 operations). Obstruction of the scrotal entrance due to abnormal Scarpa's fascia or abnormal gubernacular remnant was found in 35 and testicular absence in 15 cases. LHRH nasal spray might be effective when the testis can be manipulated to at least the scrotal entrance before treatment, but in view of our surgical findings, LHRH nasal spray will not replace orchiopexy. PMID- 3326928 TI - Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1 nitrosourea (TA-077). II. Hydrolysis by tissue homogenates and drug uptake by tumor cells in vitro. AB - 1-(2-Chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077) was hydrolyzed to its glucosyl metabolite TA-G by homogenates of guinea pig organs, rabbit VX-2 carcinoma and rat Yoshida sarcoma. The rate of TA-G formation by the kidney was the highest among the tissues examined and that by the diluted blood was undetectably low, reflecting their maltase activities. TA-077 was also hydrolyzed by suspensions of Yoshida sarcoma, AH130 hepatoma, L1210 leukemia, P388 leukemia and DBLA-10/C leukemia cells. The rate of TA-G formation was increased 10 fold by homogenizing the tumor cells. TA-G was taken up by the tumor cells much more efficiently than TA-077, explaining the higher sensitivities of the cultured tumor cells to TA-G than to TA-077. However, neither the maltase activity nor the membrane permeability to the drugs was a factor influential enough to explain the differences in drug sensitivity among the tumor cell lines. PMID- 3326930 TI - [Recent advances in immunoassay. Technical progress and its application to laboratory medicine]. PMID- 3326929 TI - Possible mechanism involved in the inhibitory action of U-50, 488H, an opioid kappa agonist, on guinea pig hippocampal CA3 pyramidal neurons in vitro. AB - Intracellular recordings of the CA3 pyramidal neurons in the guinea pig hippocampus were made in vitro. U-50 488H (100 microM), a selective opioid kappa agonist, decreased the synaptic response produced by stimulation of the mossy fibers but did not affect the membrane potential, the input resistance and the generation of the Na+ spikes or the Ca2+ spikes. Iontophoretically applied U-50 488H depressed the depolarization produced by L-glutamate. U-50 488H (100 microM) also depressed the consistent depolarization produced by veratrine (3 X 10(-5) g/ml) and this effect was partially antagonized by naloxone. Moreover, application of U-50 488H led to a disappearance of the anomalous rectification. These results suggest that U-50 488H depresses the synaptic activities of the CA3 pyramidal neurons by inhibiting a subtype of the Na+ channel, "Na+ channel type II" which slowly closes, of the soma and/or the dendrites of the neurons. PMID- 3326931 TI - Effects of sodium 5-methoxysalicylate on macromolecule absorption and mucosal morphology in a vascularly perfused rat gut preparation in vivo. AB - The effect of sodium 5-methoxysalicylate on absorption was assessed by measurement of the appearance of test compounds in the portal blood output of a perfused rat gut model. The test compounds were a hexapeptide analogue of somatostatin, insulin, and horseradish peroxidase. Considerable amounts of sodium 5-methoxysalicylate were present in the portal blood 10 min after intraduodenal administration. When co-administered with sodium 5-methoxysalicylate (60 mg), a marked increase in the concentrations of the test substances occurred at t = 15 min which lasted for a further 15 min. Quantities of less than 60 mg had much reduced adjuvant effects. In control experiments with no adjuvant, the concentrations of the test substances remained low throughout the 1-h period of blood collection. After the administration of 60 mg of sodium 5 methoxysalicylate, slight mucosal damage was apparent at 10 min. This became progressively worse with time and, at 1 h, extensive mucosal stripping had occurred. The results suggest, although they do not prove, that apparent adjuvant effects in the small intestine may be a direct consequence of serious mucosal damage. This means that care must be taken in the investigation of adjuvant properties to exclude the possibility that an observed increase in transport is due to gross loss of integrity of the membrane. PMID- 3326932 TI - [Cerebral cortical control of masticatory movements]. PMID- 3326933 TI - Psychiatric genetics and psychiatric nosology. AB - At the present time, family and twin data are used in psychiatry to test clinical concepts at issue, and, in particular, to validate or reject diagnostic classifications. The dichotomy between the schizophrenias and the effective disorders, as suggested by Kraepelin, has been supported by contemporary family and twin studies and also is corroborated by modern family and adoption studies. In the atypical psychoses it is demonstrated impressively how family data vary with different sampling procedures and diagnostic practices. In the affective disorders, the family findings at first favored the separation of unipolar and bipolar disorders but, subsequently, this concept was questioned and revised. Currently, psychiatric genetics attempts to contribute to the understanding of the affective disorders, in particular the depressions, by delineating subgroups and by looking for possible genetic relations between depression and frequently associated disorders, such as anxiety or anorexia. PMID- 3326934 TI - Problems of diagnoses in family studies. AB - This paper discusses applications of advances in psychiatric diagnostic practice to genetic research. Diagnostic misclassification and unreliability can lead to spurious conclusions about patterns of familial aggregation and co-aggregation of psychiatric disorders. Subject, occasion, information, observation and criterion variance are the major components of unreliability in diagnosis. Structured diagnostic criteria are useful for reducing errors; they may, however, lead to unjustified confidence due to their algorithmic and semi-quantitative format. Six misconceptions regarding such criteria are discussed. The choice of instruments and method of implementation must take into account the qualifications of interviewers and the need for blindness in the experimental design. A fundamental design decision in psychiatric genetic research is the choice between the family history or family study method. The costs and benefits of each method are examined. Finally, the psychiatric geneticist must face the problem of defining the ill phenotype. This is made difficult by the presence of phenocopies and the possibility that milder spectrum disorders and some symptom-free individuals may carry the genotype that underlies the phenotype of the more severe clinical form of the disorder. PMID- 3326935 TI - High-risk research in schizophrenia: a summary of what has been learned. AB - High-risk research on schizophrenia has been concerned chiefly with two types of issues: (1) description of background factors in the early lives of high-risk subjects; and (2) identification of biological variables that may be markers of the genetic liability to schizophrenic disorders. It is concluded that efforts to describe background factors have led to some conflicting results, have shown little evidence of specificity of the factors under study to risk for schizophrenia, and may not be generalizable to most individuals who develop schizophrenia. Results of research focusing on biological variables are summarized under the headings of attention and information processing (AIP), smooth pursuit eye movement (SPEM), neurological signs, electrodermal responding, event related potentials, and ventricular size. Of these, certain AIP and SPEM dysfunctions show substantial evidence of serving as biological markers, certain other AIP impairments are promising in this regard, electrodermal responsivity is not, and the other three categories present uncertain or conflicting results. Several methodological issues that have hampered the first generation of high risk research are discussed. PMID- 3326936 TI - Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia. AB - It is concluded from a review of the literature and a pilot survey that schizophrenic patients more frequently have a history of obstetric complications (OCs) than do other psychiatric patients and normal subjects. OCs are associated with increased cerebral ventricular size in both infancy and adulthood, and are more common among non-familial schizophrenic patients. Neonatal cerebrovascular events consequent upon OCs provide a mechanism to explain the increased risk of neurodevelopmental deviance and later schizophrenia. PMID- 3326937 TI - The genetics of alcoholisms and related disorders. AB - The inheritance of alcohol abuse and other psychopathology in 862 men and 913 women adopted by non-relatives, was studied. Both male and female adoptees were at greater risk to develop alcohol abuse if their biological, but not their adoptive, parents were alcoholic. Three types of families with alcoholism were distinguished that differed in frequency of alcohol abuse, somatoform disorders in women and in relation to antisocial behaviour in male adoptees. The combination of both genetic and environmental risk factors was necessary for the development of alcoholism in the most common, milieu-limited type of alcoholism. In families with a less common, male-limited, type of vulnerability, alcohol abuse was highly heritable in men, but women had multiple somatic complaints and seldom abuse. In a third type of family the common vulnerability was expressed as antisocial behavior with violent criminality and recurrent alcohol abuse in males, but as high frequency somatization in female relatives. PMID- 3326938 TI - Neurogenetic mechanisms of learning: a phylogenetic perspective. AB - Common psychiatric disorders often involve abnormal patterns of adaptive response to environmental stimuli. Thus, an understanding of the pathophysiology and inheritance of such maladaptation requires specification of the underlying neural mechanisms involved in learning, which is broadly defined as the modification of behavior as a result of individual experience. The phylogenetic development of learning ability in animals is shown to proceed by a sequence of discrete steps in which non-associative learning is augmented successively by classical conditioning to aversive stimuli, followed by classical conditioning to food and other rewarding stimuli, then exploratory learning about novel habitats and operant conditioning of behavioral responses, and finally conceptual learning ability. As a result of this complex phylogenetic history, adaptive responses to the environment in mammals including human beings is multidimensional. A model of the structure of stimulus-response and cognitive-processing characteristics in human beings is described. The model is discussed in terms of its evolutionary advantages for survival and reproductive fitness as well as its importance in understanding susceptibility to psychiatric disorders, including personality and anxiety disorders. PMID- 3326939 TI - Studying biological vulnerability and heterogeneity--a long way ahead. AB - Common diseases are usually the consequence of a variety of etiologies. This rule applies, for example, to mental retardation and epilepsy. There is evidence that genetic factors influence the propensity to utilize alcohol on an addictive basis at two levels of interaction between the drug and the body. It is doubtful that psychiatric symptoms are specific for defined etiologies. Individuals who are heterozygous for autosomal-recessive alleles may show slight deviations toward the homozygous genotype. These findings are applied to a polygenic concept of psychiatric disorders. Data are presented that would be compatible with a slightly increased incidence of heterozygotes for Wilson's disease and metachromatic leucodystrophy in psychiatric patients. PMID- 3326940 TI - The outlook for linkage research in psychiatric disorders. AB - Analysis of the distribution of diagnoses in families (segregation analysis) has not, so far, advanced us toward the goal of resolving the inheritance of the major psychiatric disorders. Recent advances in genetics, particularly the development of new molecular genetic linkage methods, have made it, at least theoretically, feasible to scan the entire human genome, so that in a properly designed and executed set of studies it will be possible to demonstrate whether there exists single locus transmission for a particular disorder, and to map the locus. We present here an analysis of feasibility of moderate-sized pedigrees (approximately 15 persons, two generations) and affected-sib-pair sets in such studies. Eight to ten moderate-sized pedigrees are sufficient to perform definitive mapping under the tested conditions, of recessive or additive inheritance, low penetrance of the heterozygote, and a genetically homogeneous disorder. The affected-sib-pair method required 25 pairs of sibs to detect linkage under such conditions in a recessive model, and 45 in a dominant model. When there is genetic heterogeneity, moderate-sized pedigrees are much less useful, but the affected-sib-pair method retains considerable power. PMID- 3326941 TI - Research design considerations for linkage studies of affective disorders using recombinant DNA markers. AB - A genetic linkage study is one approach to resolving the etiology of a major psychiatric disorder either by testing involvement of a specific candidate gene or by demonstrating the existence of some unidentified gene in a specific place on the genome. Because of the complexities of psychiatric disorders, a successful linkage study must be built upon accurate and reliable diagnosis, families with multiple affected members, highly informative genetic markers, and powerful multipoint linkage methods. Over the last decade, great advances have been made in all these areas. Linkage studies are not only appropriate for affective and other major psychiatric disorders but are already beginning to yield promising results. PMID- 3326942 TI - Genetic linkage: sampling issues and multipoint mapping. AB - Genetic linkage is an important tool in determining the genetic contribution to the etiology of behavior disorders and psychiatric disease. Successful linkage studies employ large sample sizes. It is of particular relevance in psychiatric diseases, where the clinical workup is so extensive, to evaluate sample requirements critically. Recent studies indicate that extensive sampling, out to second-degree relatives, will not assist in identifying linkages although it may inflate the sample size considerably. The impact of the assumption about the mode of inheritance of the psychiatric trait and the effect of reduced penetrance are discussed. Multipoint mapping has the added advantage of using information from many markers simultaneously. This is helpful both in identifying individuals at risk to develop disease and in locating a gene with sufficient precision to determine the gene product. There are complications in applying multipoint mapping but these are generally of a technical nature and soluble. Recent suggestions for handling complications for multipoint mapping are evaluated. The correct design of the sampling procedure for selecting families and for selecting marker loci to use will greatly reduce the volume of work required for linkage studies and enhance the chances for success. PMID- 3326944 TI - A new technique of oesophagogastric anastomosis using autosuture stapling equipment. PMID- 3326943 TI - Treatment of displaced subcapital femoral fractures by primary total hip replacement. PMID- 3326945 TI - Two cases of aneurysm of the inferior pancreatico-duodenal artery: a review of treatment. PMID- 3326946 TI - Smokeless tobacco--health hazards from a good 'ole habit. PMID- 3326948 TI - Biomechanical aspects of playing surfaces. AB - The purpose of this paper is to discuss some biomechanical aspects of playing surfaces with special focus on (a) surface induced injuries, (b) methodologies used to assess surfaces and (c) findings from various sports. The paper concentrates primarily on questions related to load on the athlete's body. Data from epidemiological studies suggest strongly that the surface is an important factor in the aetiology of injuries. Injury frequencies are reported to be significantly different for different surfaces in several sports. The methodologies used to assess surfaces with respect to load or performance include material tests and tests using experimental subjects. There is only little correlation between the results of these two approaches. Material tests used in many standardized test procedures are not validated which suggests that one should exercise restraint in the interpretation of these results. Point elastic surfaces are widely studied while area elastic surfaces have received little attention to date. Questions of energy losses on sport surfaces have rarely been studied scientifically. PMID- 3326947 TI - Dual level control of the Escherichia coli pheST-himA operon expression. tRNA(Phe)-dependent attenuation and transcriptional operator-repressor control by himA and the SOS network. AB - Previous studies of phenylalanyl-tRNA synthetase expression in Escherichia coli have established that the pheST operon transcription is controlled by a Phe tRNA(Phe)-mediated attenuation mechanism. More recently, the himA gene, encoding the alpha-subunit of integration host factor, was recognized immediately downstream from pheT, possibly forming part of the same transcriptional unit. By using the in-vitro transcription and S1 mapping techniques, transcription termination after pheT could be excluded, indicating that himA can be expressed from polycistronic messenger RNAs encompassing the pheST region. However, the presence of a secondary promoter able to express himA and located within pheT is demonstrated. To further investigate the regulation of the pheST-himA operon expression, genetic fusions between various parts of this operon and the lacZ gene were constructed and studied. Our results confirm the autoregulation of himA previously described, and demonstrate that it occurs through the modulation of the secondary promoter activity within pheT. Surprisingly, it is found that the pheST promoter is also submitted to the same control. Consistent with this, DNA sequences homologous to the integration host factor binding site consensus are present at the level of both promoters. However, evidence in favor of two different repressor complexes is provided. Previously observed SOS induction of the himA expression is shown to occur through the modulation of both promoter activities. Contrasting with the other genes under SOS control, the LexA protein binding site consensus sequence could not be found in the two promoter regions. This suggests that either the LexA protein directly participates in the formation of an active holorepressor, or that the product of an SOS gene is able to inhibit the formation or the binding of such a repressor. Finally, our results indicate that the pheST-himA operon expression is controlled by two different mechanisms acting independently. (1) The phenylalanyl-tRNA synthetase and the himA product expressions are controlled by an operator-repressor type mechanism, in which the himA product and the SOS network are involved. (2) Through its partial cotranscription with pheST, himA expression is also under attenuation control. The latter control may provide a way to couple the intracellular concentration of the himA product to the functional state of the translational apparatus. PMID- 3326949 TI - Bone dynamics: stress, strain and fracture. AB - Bone is a dynamic tissue whose functional mass is controlled by the balance between the endocrine drive towards bone resorption and the mechanically engendered drive towards bone formation. Strain is the key intermediate variable between loading forces and bone remodelling. Animal studies have shown that static loading of bone has no osteogenic effect; bone loss occurs as if there were no loading at all. However, dynamic loading, that is, cyclic change in internal strain, is strongly osteogenic, with relatively few cycles required for maximum effect. However, if a sufficient number of cycles is applied, repetitive loading can cause stress fractures. This number decreases as internal strains increase. Thus strain redistribution within bone, as caused by muscle fatigue or improper sports equipment, is a significant cause of fracture. PMID- 3326950 TI - [Immunohistochemical observation of infiltrated lymphocytes in squamous cell carcinoma]. PMID- 3326951 TI - [A case of eosinophilic peritonitis]. PMID- 3326952 TI - [A case of ulcerative colitis associated with asymptomatic primary sclerosing cholangitis, the lesion of which extends from intrahepatic bile duct to extrahepatic bile duct]. PMID- 3326953 TI - [Urinary excretion of kallikrein and prostaglandins before and after sodium deprivation and their relationships to plasma vasopressive substances]. PMID- 3326954 TI - [Plasma renin substrate in normal subjects and various diseases--influence of sodium chloride and various medicines]. PMID- 3326955 TI - [The effect of inhibitor of angiotensin-converting enzyme on uric acid metabolism]. PMID- 3326956 TI - [Parapelvic renal cyst is almost asymptomatic, so clinical case is rare]. PMID- 3326957 TI - [Development of a CRT-diagnosis system in nuclear medicine using a personal computer]. PMID- 3326958 TI - [Diagnosis of Pseudomonas pneumonia at autopsy by immunofluorescent-staining with monoclonal antibody]. PMID- 3326960 TI - [Review: tracheobronchoplasty]. PMID- 3326959 TI - [Benign clear cell tumor of the lung: a case report]. PMID- 3326961 TI - A molecular biological approach to the study of anion transport. PMID- 3326962 TI - Membrane receptors that mediate glycoprotein endocytosis: structure and biosynthesis. PMID- 3326964 TI - [Biology, epidemiology and pathobiology of Toxoplasma gondii (Nicolle and Manceaux 1908)]. PMID- 3326963 TI - The molecular biology of insulin action on protein synthesis. PMID- 3326966 TI - [Development of a national medico-scientific society of pediatricians in East Germany. 2. Stages in the formation of the Society of Pediatrics of East Germany and its forerunners following the Weimar Health conference 1960]. PMID- 3326965 TI - [Metabolic adaptation in the fasting test in children with glycogenosis type I]. PMID- 3326967 TI - [Keratoplasty in children and adolescents]. AB - In a retrospective study 37 penetrating keratoplasties performed on 33 eyes of 29 patients under age 12 were evaluated. One year postoperatively, 19 of 35 grafts were clear and 16 of 35 had failed. In the group aged under 3, most of whom had congenital anomalies, 4 of 14 had clear grafts and 10 of 14 failed grafts after one year. Two patients were not investigated one year after keratoplasty, but probably had cloudy grafts at that time. Loosening of the sutures and keratitis were the main complications in the postoperative course. Graft rejection was clinically diagnosed in 11 of 37 cases. PMID- 3326968 TI - ["Umbrella syndrome," a contribution to pseudoretinoblastoma]. AB - In two children referred to the author's clinic because of suspected retinoblastoma, pathologic fibroglial tissue was observed unilaterally in front of the macula and optic disk. Fluorescein angiography and ultrasonography indicated a posterior PHPV. In view of the morphological appearance the condition was termed "umbrella syndrome". There were no therapeutic consequences. PMID- 3326969 TI - [Digital subtraction dacryocystography]. AB - A comparison of 17 radiological examinations of the lacrimal pathways performed on twelve patients using digital subtraction and conventional film technique showed that digital subtraction dacryocystography yields images of superior quality. Digital subtraction makes enhanced imaging of the opacified tear duct as well as elimination of super-imposing skeletal structures possible, which with conventional techniques frequently impair diagnostic accuracy. In measurements of the radiation dose sustained by the crystalline lens, the radiation level with digital subtraction was found to be considerably lower than with the conventional method. PMID- 3326970 TI - [Pilots through 125 years of ophthalmologic science and practice. Karl Wilhelm v. Zehender (1819-1916)]. PMID- 3326972 TI - Healthful school living: environmental health in the school. AB - The author defines environmental health as it relates to schools, and identifies site, chemical, biological, and physical environmental health hazards. Recommendations and precautions to help achieve optimal health, safety, and comfort are presented. Resources from which personnel can get assistance to help improve the environmental health of their schools are noted. PMID- 3326973 TI - Integrated school and community programs. AB - Collaboration and coordination among school nurses, health teachers, guidance counselors, food service directors, principals, administrators, parents, and community agencies have the potential to upgrade school health programs. Benefits derived from an integrated school and community program are documented. Three models that have effectively brought together schools and community agencies are described. PMID- 3326974 TI - School health promotion: child nutrition programs. AB - Since 1946, with the enactment of the National School Lunch Act, an important and integral part of the comprehensive school health program has been ensuring the nutritional needs of students are met. This article describes the history of the school nutrition program and how it has adapted to meet the needs of today's students. The modern menu is more healthful, foods are prepared with less salt, sugar, and fat, and nutrition education complements food choices. Through collaboration, nutrition education has been integrated into health education and the other elements of the total school health program to better meet students needs. PMID- 3326971 TI - School health education: a foundation for school health programs. AB - This article describes the present status of health instruction--one of the original three components of the school health program--and suggests ways to improve its effectiveness as one of the eight components of a comprehensive school health promotion program. The article also demonstrates the complexity of the theory base, content, methodology, and outcome expectations of health instruction; a complexity that demands the subject be taught by teachers who are thoroughly prepared and committed to teaching health. PMID- 3326975 TI - Plants used in traditional medicine in eastern Tanzania. I. Pteridophytes and angiosperms (Acanthaceae to Canellaceae). AB - Seventy-seven plants are listed, which are used by traditional healers in five regions of eastern Tanzania, Coast, Dar es Salaam, Kilimanjaro, Morogoro and Tanga. For each species are given the botanical name, vernacular name, collection number, locality, habit, distribution and medical uses. Results of a literature survey are also reported, including medical use, isolated constituents and pharmacological effects. PMID- 3326977 TI - Becoming a father: a review of nursing research on expectant fatherhood. AB - A review and analysis of nursing research focused on understanding the experiences of men becoming fathers is presented. Designs, sampling, methods, and substantive findings of the research studies are summarized. Implications for nursing are given. PMID- 3326976 TI - Blood pressure and plasma renin activity after magnesium supplementation in the spontaneously hypertensive rat: a study during developing and established hypertension. AB - The effects of a dietary magnesium supplementation have been studied both on systolic blood pressure and plasma renin activity in the spontaneously hypertensive rat (SHR). This study has been conducted in young (developing hypertension) and mature (established hypertension) male SHR fed during 6 weeks with a normal magnesium diet or with a high magnesium diet. After 6 weeks of diets, the systolic blood pressure was lower in young and mature SHR fed with an increased dietary amount of magnesium than in the young and mature SHR fed with a normal amount of dietary magnesium. Plasma renin activity was similar after the two different diets in young SHR while it was greater in mature SHR receiving a high magnesium diet than in mature SHR receiving a normal diet. Hence, dietary supplementation with magnesium inhibits the development of hypertension in young SHR, and reduces arterial blood pressure in mature SHR. The hypotensive effect observed during magnesium supplementation is not related to an inhibition of the renin release. PMID- 3326978 TI - Quantifying risk and accuracy in cancer risk assessment: the process and its role in risk management problem-solving. AB - A better understanding of chemical-induced cancer has led to appreciation of similarities to problems addressed by risk management of radiation-induced toxicity. Techniques developed for cancer risk assessment of toxic substances can be generalized to toxic agents. A recent problem-solving approach for risk management of toxic substances developed for the U.S. Department of Health and Human Services, and the role of risk assessment and how uncertainty should be treated within the context of this approach, is discussed. Finally, two different methods, research into the assumptions underlying risk assessment and the modification of risk assessment/risk management documents, are used to illustrate how the technique can be applied. PMID- 3326979 TI - Cancer and leukemia risks after low level radiation--controversy, facts and future. AB - Quantification of delayed low dose radiation (LDR) effects is still controversial. The current concept of the shape of the dose-response curve, particularly at the very low levels, is derived primarily by extrapolation from high doses and is affected by economic, social and political implications of cancer yield. Evidence based on epidemiological studies of populations exposed to fallout, occupational, intrauterine or background LDR is limited, due to methodological drawbacks and the need for extremely large sample sizes. Nevertheless, recent data indicate that LDR-induced childhood leukemia and thyroid cancer may exceed the rates predicted on the basis of the linear quadratic curve. The high yield in utero and in early childhood could be associated with low cumulative load of background radiation, and a consequently more effective radiation increment. A long term follow up of children exposed to 90 mSv after scalp X-irradiation revealed a relative risk of 3.8 and an excess risk of about 1.08 per 1000 man-sievert per year for thyroid cancer. Application of these findings to the post-Chernobyl state of events suggests that an increment of up to 20% in thyroid cancer might occur in a population exposed to 5 mSv as an aftermath of a similar accident. Prediction of future risk estimates should therefore be made with alertness and an open mind. PMID- 3326981 TI - Have we reduced the risk of getting cancer or of dying from cancer? An update. AB - We have examined trends in cancer mortality, incidence and survival in the United States to update our earlier work and respond to criticisms. [Bailar, J.C., Smith, E.M.: New Engl. J. Med. 314, 1226 (1986).] Here we concentrate on the years 1975-1984, and show that overall cancer mortality has increased, incidence has increased and case survival is virtually unchanged. This generally unfavorable picture is scarcely changed when lung cancer is excluded from the trends. While trends for individual cancers have been mixed, overall progress in both curative treatment and prevention has been minimal. This evaluation does not deny the marked progress in treating some uncommon forms of cancer, improved palliation, reduced extent or severity of treatment, or benefits of cancer research that can be applied in other areas of medicine. While our finding of limited progress is not new, we believe that it requires increased attention in setting the course of future research initiatives, demonstration programs, medical training and clinical practice. PMID- 3326982 TI - Leukaemia and lymphoma risks derived from solvents. AB - Results of epidemiologic studies indicating an association between solvent exposure and the development of malignancies affecting haematopoietic and lymphatic tissues are reviewed. Clinical and cytogenetic data supporting this association are discussed. A variety of malignant disorders have been associated with solvent exposure, i.e. acute leukaemia, Hodgkin's disease (odds ratio 2.8 6.6), non-Hodgkin's lymphoma (odds ratio 3.3) and myeloma, and there are some indications that solvent exposure may be a risk factor for myelofibrosis. The carcinogenic effect of benzene is epidemiologically and experimentally well documented and there are some indications that other solvents may also be hazardous. Possible mechanisms bringing about malignant transformation are discussed. The need for further epidemiologic, cytogenetic and clinical studies on the association between solvent exposure and malignant diseases is emphasised. PMID- 3326984 TI - Towards the reduction of lung cancer. AB - The epidemiology of lung cancer clearly demonstrates the preventive opportunities that exist for major causes of cancer death. We have the opportunity to affect lung cancer rates by reducing the effects of smoking. Such activities, in increasing order of importance, include low-yield cigarettes, tobacco smoking cessation and tobacco smoking prevention. Within a community these activities could best be conducted and carried out through a Disease Prevention Unit (DPU), the nature of which is briefly described in this paper. PMID- 3326985 TI - Nutritional cancer risks derived from energy and fat. AB - Both animal and human studies indicate that increased caloric intake and increases in body weight and obesity are associated with increased risk of cancer of the breast, endometrium, ovaries, colon, rectum and prostate. Recent animal studies indicate that it is the total caloric intake, rather than the percent of fat in the diet, that is associated with tumorigenesis and carcinogenesis, and that tumor development depends on a complex interaction involving energy intake, energy expenditure, energy retention within the body (body fat vs lean body mass) and body size. Omega-3 fatty acids inhibit tumorigenesis and tumor growth in many cancer models in rodents. Exercise diminishes tumor formation in mice, rats and humans. Exercise delays mortality from all causes, and life-long exercise is associated with decreased cancers of the breast and reproductive system in women, and cancer of the colon in women and men. PMID- 3326980 TI - Cancer genes generated by rare chromosomal rearrangements rather than activation of oncogenes. AB - The 20 known transforming onc genes of retroviruses are defined by sequences that are transduced from cellular genes, termed proto-oncogenes or cellular oncogenes. Based on these sequences, viral onc genes have been postulated to be transduced cellular cancer genes and proto-onc genes have been postulated to be latent cancer genes that can be activated from within the cell to cause virus-negative tumors. The hypothesis is popular because it promises direct access to cellular cancer genes. However, the existence of latent cancer genes presents a paradox since such genes are clearly undesirable. The hypothesis predicts (i) that viral onc genes and proto-onc genes are isogenic, (ii) that expression of proto-onc genes induces tumors, (iii) that activated proto-onc genes transform diploid cells upon transfection, like viral onc genes, and (iv) that diploid tumors exist that differ from normal cells only in transcriptionally or mutationally activated proto-onc genes. As yet, none of these predictions is confirmed. Moreover, the probability of spontaneous transformation in vivo is at least 10(9) times lower than predicted from the mechanisms thought to activate proto-onc genes. Therefore the hypothesis, that proto-onc genes are latent cellular oncogenes, appears to be an overinterpretation of sequence homology to structural and functional homology with viral onc genes. Here it is proposed that only rare truncations and illegitimate recombinations that alter the germline configuration of cellular genes, generate viral and possibly cellular cancer genes. The clonal chromosome abnormalities that are consistently found in tumor cells are microscopic evidence for rearrangements that may generate cancer genes. The clonality indicates that the tumors are initiated with, and possibly by, these abnormalities as predicted by Boveri in 1914 (Zur Frage der Entstehung maligner Tumoren, Jena, Fischer). PMID- 3326986 TI - Cancer risks derived from alcohol. AB - Most cancers of the upper aero-digestive tract are related to alcohol consumption. For the mouth, oesophagus and larynx a positive dose-response relationship has been observed, as well as a combination effect with tobacco smoking--according to a multiplicative model in the case of the oesophagus. Nutritional factors also play a role. For other cancer sites, the role of alcohol is controversial, except for primary liver cancer which often develops on a cirrhotic liver. The mechanisms by which alcohol increases cancer risk are still obscure. It is not considered to be a carcinogen by itself but rather as a co carcinogen, facilitating or enhancing the role of other carcinogens. Another mechanism might be the induction of microsomal enzymes activating pro carcinogens. As in the case for smoking, prevention can be achieved by abstention or reduction of consumption. This has to be considered seriously in countries where alcohol consumption is increasing. PMID- 3326983 TI - Pesticides and cancer risks in agriculture. AB - The work environment in agriculture is complex, with many potentially hazardous exposures, but the overall mortality from cancer and other causes is rather low among farmers. However, several studies have consistently indicated an excess of certain cancer forms. Lymphomas, leukemias, multiple myeloma and also malignancies of connective tissue attract special interest, as being possibly associated with the use of pesticides. Phenoxy acid herbicides may play an etiological role, especially for non-Hodgkin's lymphoma, whereas the findings are more ambiguous for Hodgkin's disease and soft-tissue sarcoma, perhaps indicating an interaction with co-factors. The issue has been controversial for many years, however, and one of its aspects involves the use of phenoxy acids in the Vietnam war. Furthermore, DDT has been associated with lung cancer in mixed exposure situations, and with chronic lymphatic leukemia. Arsenical pesticides may have caused skin cancer in vine-growers. Further studies, especially of specific user groups and producers, may avoid the complex exposure situation in agriculture. PMID- 3326988 TI - Psychological reactions to cancer risks after the Chernobyl accident. AB - This is a report on an investigation of people's reactions to the Chernobyl accident. Interviews and mail surveys were conducted in July-September 1986 with pregnant women, parents of newborn children, farmers, adolescents and men who were not parents, in various areas of Sweden, differing as to the amount of Chernobyl fallout they had received. The accident had probably doubled the number of people who were negative to nuclear power in the most affected area. Radiation risks were highly salient in most groups. Areas differed in the expected direction, people in the more exposed areas being more concerned. Women were more worried and more negative to nuclear power than men while adolescents appeared to be the group least affected by the accident. Farmers were also strongly opposed to nuclear power and concerned about its risks. Nuclear attitude could be well accounted for by attitude statements and rated basic life values. It was quite stable over a 1 month period. PMID- 3326990 TI - Changes in insulin secretion and calcium distribution within B cells induced by gliclazide. AB - Using the pyroantimonate technique, the ultracytochemical distribution of calcium within B cells was studied in isolated rat pancreatic islets incubated during 5, 15 and 30 min with 8.3 mM glucose alone or together with 76 microgram glicazide. Glucose alone produced a continuous increment in the total number of calcium pyroantimonate precipitates (CPP) throughout the incubation period studied. The CPP were mainly associated to the cytoplasmic matrix and the secretory granules at 5 and 15 min and almost evenly distributed between these structures and the plasma membrane at 30 min. Gliclazide plus glucose produced a significant increment, above the glucose values, of the total CPP at 5 min and a later decrease of such values at 15 and 30 min. At 5 min, the incremented total CPP was mainly associated to the secretory granules and the cytoplasmic matrix. The increment in CPP preceded the largest effect of gliclazide on insulin secretion. The latter diminution of CPP induced by gliclazide could contribute to the failure of this drug, as well as other oral hypoglycemic agents, to elicit a second phase of insulin secretion. Changes induced by gliclazide upon B-cell CPP content and distribution might suggest that beyond the effective role of cytosolic calcium in the control of insulin secretion, the cation might reach a threshold concentration in some cell structures to assure the normal development of the secretory process. PMID- 3326989 TI - Cancer risks and cancer prevention in Sweden. AB - Sweden has had cancer and population registers since 1958, indicating an increasing total age-adjusted cancer incidence. The incidence of liver, prostate and urinary tract cancer, as well as of melanoma and lymphoma, is increasing, whereas that of stomach cancer and Hodgkin's lymphoma is decreasing. National public recommendations by the nutrition and exercise committee of the National Board of Health and Welfare to reduce fat, salt, energy and sugar intake and to increase fiber intake and exercise have existed for 20 yr. The purpose was initially to prevent cardiovascular diseases, later also to prevent breast and prostatic cancer. Since the 1970s, Swedish women have been offered systematic gynecological health checks, resulting in a reduced incidence and mortality of cervix carcinoma. Local Swedish studies suggest that systematic mammography, which is now recommended on a national basis, can reduce breast cancer mortality by 30%. It is estimated that between 300 and 1100 cases of bronchopulmonary carcinoma are partly caused by a dwelling environment with over 400 Bq radon m-3. General rebuilding of the 40,000 houses concerned is at present being considered. PMID- 3326991 TI - [70th anniversary of the Great October Revolution]. PMID- 3326987 TI - The iatrogenic leukaemias induced by radio- and/or chemotherapy. AB - A short review, limited to recently published series of data, has been compiled on the 'therapy-induced' secondary malignancies. Their frequency, peak of incidence, haematological and clinical criteria, the influence of age, treated primary disease, choice of drug(s) and modality of prescription and the role of genetic and environmental factors are analyzed. The risk varies between 0.6 and 20.5% after different treatment forms. Some suggestions for the choice of treatment of chronic malignant disorders, and for the design of future epidemiological studies are given. PMID- 3326992 TI - [Partisan--nurse Elena Struk]. PMID- 3326993 TI - [Basic parameters and testing methods for medical roentgen screens]. AB - The basic parameters characterizing the optical properties of the roentgen screens of all types included in the CMEA Standards and GOSTs have been considered. The classification of screens is given. The measurement principles for the absolute and relative characteristics of their effectiveness are described. The properties of the screens determining their effect on the image quality such as the definition of the picture, the graininess and the minimal size of observed details have been considered. The methods of controlling the persistence of the screens and the presence of radionuclide tracks have been described. PMID- 3326994 TI - Alternating versus sequential therapy in advanced breast cancer. PMID- 3326995 TI - [ABO incompatible renal transplantation of a related living donor]. PMID- 3326996 TI - [Hepatic abscesses and sepsis in a young man]. PMID- 3326997 TI - [A new approach to immunotherapy of cancer based on autologous T-lymphocytes]. PMID- 3326998 TI - [Analysis of the metastatic process]. PMID- 3326999 TI - [Therapy and prevention of infectious endocarditis in adults]. PMID- 3327000 TI - [The Stomatology Section of the Medical Society of Vojvodina (1962-1987)]. PMID- 3327001 TI - Ultrasonic tissue characterization and echographic imaging. AB - In this survey paper it is attempted to present the state of the art in ultrasonic tissue characterization. Analysis of raw radiofrequency data allows for the estimation of acoustic tissue parameters like velocity, attenuation and backscattering. It is argued that prior to analysis and processing of two dimensional (i.e. B-mode) echographic images corrections for the influences of equipment, sound field and intervening tissue are absolutely necessary. Then promising characteristics of tissue structure can be derived from texture analysis. Postprocessing of echographic images till now did not yield valuable results. Synthetic aperture systems and computerized tomography techniques may bring a break-through. PMID- 3327002 TI - Analysis with solid phase reagent carriers. AB - Solid-phase chemistry is a category of analytical techniques characterized by three features: dry reagents fixed on or in an inert carrier; they are transformed into a liquid state of reactivity solely by fluid from the sample, movement of fluid in the carrier happens through capillary surface forces. A number of industrial laboratories have adapted these technologies to a majority of parameters of blood or serum respectively. The most frequently used measuring devices are new developed reflectometers; in one system (Ektachem) disposable ion selective electrodes have been newly developed in addition. The most important systems on the market are Ektachem (Kodak), Reflotron (Boehringer, Mannheim) and Seralyzer (Ames). These systems differ with respect to the construction of the reagent carriers and of the reflectometers. Solid-phase chemistry has the following advantages over the conventional analytical techniques: The sample volume is small, and the instrumentation is not complicated. The reagents are ready for use, and one system permits the use of whole blood without centrifugation. In this way it is possible to perform decentralized analyses at the patient's bedside, or in the physician's office. The disadvantages are the complete dependency of the user on the manufacturer with respect to the methodology and the quality of the reagents and instrumentation, the relative high price of the test-elements, and the limited possibility for the processing of long series. Additional problems are associated with quality control and drug interference. Nevertheless it can be expected that in the future increasing numbers of clinical chemical analyses will be performed by solid-phase chemistry, especially in general practice. PMID- 3327003 TI - Biophysica and medical aspects of fast NMR-imaging. AB - Nuclear magnetic resonance (NMR) imaging is a promising new technique for non invasive medical diagnosis. Following a decade of technical improvements and preliminary medical experiences, the measuring time of several minutes remained the major drawback of the method. The recent development of a fast NMR-imaging technique, the so-called FLASH (Fast Low Angle SHot) method, opens a new field of medical applications. This article deals with a few applications and aspects of FLASH imaging. Using the technique cross-sectional images can be taken within a few seconds without loss in spatial resolution. Therefore dynamic investigations of the function of internal organs and images of blood vessels become possible. Furthermore three-dimensional volume imaging of the whole object provides the full anatomical information. FLASH imaging is also applicable in combination with localized NMR-spectroscopy. Thus, biochemical information from NMR-spectroscopy and structural and functional information from NMR-tomography can easily be combined. PMID- 3327004 TI - History of black mortality and health before 1940. AB - This article documents the history of black mortality between 1850 and 1940 and begins the process of placing that history into the context of the more general history of mortality decline in the United States. One aspect of this process has been to discuss the trends in mortality among blacks and whites living in the same general geographic areas--for example, comparing southern rural blacks with southern rural whites. A second part has been to relate black mortality to many of the factors that have been discussed as determinants of general mortality trends--such as water and sanitation, the urban disadvantage in mortality, and child care and feeding practices. During the second half of the nineteenth century, black mortality declined only slightly or not at all. Between 1850 and 1880 there may have been some decline in child mortality, but the trends in adult mortality are indeterminate. Between 1880 and 1900 both child and adult mortality rates were constant. Sometime between 1900 and 1910 mortality rates among blacks began to decline at all ages, especially in urban areas. During the first four decades of this century mortality rates among American blacks declined substantially. Expectation of life at birth increased from about 35 years to about 54 years, which represents a significant improvement in health and living standards. The life expectancy among blacks in 1940, however, was still two years below the value for whites in the death registration area in 1920. (This may exaggerate the difference slightly since the mortality rates for 1919 and 1920 were artificially low following the pandemic of influenza in 1918. In addition, the mortality rates in the DRA may not have been representative of the whole white population.) Throughout the period studied, blacks had substantially higher mortality rates than whites living in the same area. Although the amount of excessive mortality among blacks differed from place to place and period to period, we did not find a single area or time when black mortality rates were close to those of whites. The examination of causes of death among whites and blacks in 1920 showed that racial differences in the amount of tuberculosis explained a substantial part of the mortality differences in New York and North Carolina, but blacks probably had excessive mortality due to all causes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327006 TI - Public versus employment-related health insurance: experience and implications for black and nonblack Americans. AB - Despite a complex web of private and public health insurance programs, over 6 million black and almost 31 million nonblack Americans were uninsured in 1985. Although the situation since 1980 had deteriorated relatively less for them, nonelderly blacks remained 1.5 times more likely to be uninsured. Because of differences in family structure and economic circumstances, blacks less frequently have employment-related insurance and are more often covered by a public program. Mandated employment-related insurance is less likely to benefit blacks than would expansion of Medicaid. A combined approach may be needed to reduce the total number of uninsured Americans. PMID- 3327005 TI - Health differentials between blacks and whites: recent trends in mortality and morbidity. AB - Black Americans continue to have large numbers of premature and excess deaths, measured against white experience, from seven major causes. Major differences in chronic disease, disability and case fatality rates persist despite similarities in the amount of health care received; the nature and quality of care is likely to be dissimilar. Epidemiological and clinical evidence suggests various strategies to reduce these differentials through well-designed public health efforts at prevention. These will have to deal with harsh realities of sociocultural, economic, and political contexts. PMID- 3327007 TI - Health care for black Americans: the public sector role. AB - Most of the improvement--both absolute and relative--in the health status of black Americans over the past two decades can be traced to major gains in access to health care services. Public payment programs, most notably Medicaid and Medicare, have not only reduced financial barriers, but have also combatted those of racial discrimination. Other federal programs supporting targeted local services have been especially effective in reducing infant mortality. But the redistributive effects have been uneven and unequal across populations; many categorical gaps remain and increasing numbers are potentially without access to essential primary care services. PMID- 3327008 TI - Black demographic trends in the 1980s. AB - Most of the black demographic trends witnessed in the 1970s have continued during the first half of the 1980s, but the pace of demographic change has slowed in some areas and quickened in others. A short summarization of the major trends is provided below; 1. The black population is growing faster than the white population and blacks are becoming a larger share of the total population. 2. Blacks continue to move out of the North and into the South and West. 3. Blacks continue to move out of central cities into suburbs, but blacks are not moving out of central cities as fast as whites and central city populations are becoming increasingly black. 4. The growth rates of preschool-age blacks increased in the 1980s, but the growth rates of the school age and young adult populations declined. 5. The fertility rates of blacks continued to fall and to approach convergence with those of whites, although there still is a significant gap between black and white fertility rates. 6. Teen birthrates for unmarried blacks continued to fall during the first half of the 1980s. 7. Life expectancy for blacks continued to increase during the 1980s, but at a somewhat slower pace than seen during the 1970s. 8. The share of black children living in single parent families continued to grow during the 1980s at a faster rate than seen during the 1970s. 9. The share of black children living with a never-married parent grew much more rapidly in the 1980s than in the 1970s. PMID- 3327009 TI - Conceptual and methodological issues in the use of race as a variable: policy implications. AB - The history, reality, and prolonged effects of racial stratification and its supportive ideology in the United States require systematic study of the impact of racial perceptions in the health sphere and in every facet of American life (Berry 1965; Berreman 1985; Blackwell 1985). In this regard, the use of race as an independent variable in social research is, in principle, similar to the presumed explanatory power of other status characteristics such as class or economic position. Depending on which meaning is intended, the potential policy, health services, and sociopolitical outcomes could be diametrically opposed to one another. Far from being an esoteric subject among intellectuals, any definition of race has fundamental and practical extensions to cultural and political realities. Essentially, studies and discussions of racial similarities and differences in health matters, whether intended or not, go beyond statistical compilations and correlations and reflect norms, values, the country's common beliefs (Praeger 1982), and the structural positions of majority and minority groups. Presumably, these are among the reasons that racial categories are studied in social science. They are assumed to represent socially relevant and unique histories, experiences, and statuses which differentiate black and white Americans in particular. The risks in epidemiologic and in social science research involve the preoccupation with disparities in the health difficulties among them; the attribution of racial biology and genetic traits to virtually all health spheres; the assumed preponderance of disabling conditions for blacks; and the unrelenting focus on only two racial populations despite our having a multiethnic society (Wilkinson 1987). Since health behaviors are directly associated with a group's "way of life," they should be carefully scrutinized within relevant socio-environmental contexts as part of the scientific processes of discovery, for the underlying premises, ideological translations, and practical applications of their studies especially with respect to race-specific health research. It is likely that systematic probing beyond demographic or constitutional factors will enable social scientists and health researchers to discover that for certain behaviors (e.g., prevention), individual attributes such as race and sex--and even knowledge, roles, attitudes, and diets--may explain far less than will environmental hazards and basic structural variables such as the organization of the health care delivery system, availability of and access to care, ability to pay, provider patterns, diagnostic processes, institutional operations, and quality of care.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327010 TI - Black-white differences in health status: methods or substance? AB - Apparent differences in the health status of blacks and whites vary according to methods of measurement, errors in the measurement process and interpretation of the measures, and types of measures used. This article uses the literature and secondary analysis of available data to explore the impact of methods on health status comparisons by race. Methods to measure health status include records, direct observations, and self-reports. Blacks generally show the greatest health deficits based on observation and least on some types of self-reports. Major types of errors in health status estimates are random errors and biases. Random errors tend to be greater for blacks because samples used to estimate their characteristics have often been smaller than white samples. Biases include noncoverage or failure to include some types of individuals in the reporting systems at all, nonresponse or lack of complete information on some persons, and use of inaccurate information due to faulty data collection or processing. Such biases tend to be greater for black persons than for whites. Their impact often is to give the illusion that blacks may be in better health than is actually the case. The types of measures that show blacks in the poorest health status are those considered to be most objective: mortality rates and some clinical examinations and health provider records. Subjective measures of dissatisfaction with health level also show blacks to be much less healthy than whites. In contrast, self-reports of illness conditions, symptoms, and restricted-activity days show blacks, particularly children, to be relatively well off compared to whites. These self-reports may be misleading due to differential perceptions of illness and reporting biases between blacks and whites. There is no doubt that measured differences in the health status of blacks and whites often reflect substance. There are also significant methodological problems, however, in comparing health status by race, which tend to underestimate the problems experienced by the black population. This article and others in this volume stress the need to know much more about the sources and impact of these methodological problems. In the meantime, these problems need to be recognized and adjusted for, where possible, when health status measures are compared. It is particularly important to consider them when policy questions of equity and resource allocation are to be decided using indicators of health status. PMID- 3327011 TI - The quality of life for black Americans twenty years after the civil rights revolution. AB - The United States has an extensive statistical system that generates hundreds of indicators of the health and economic status of its population components. Yet, there is no consensus about how different indicators should be weighted and interpreted to judge the absolute and relative progress of black Americans. Neither a "melting pot" nor a "polarization" model adequately describes the conflicting areas of gain, pervasive stagnation, and substantial loss in racial equality of life. PMID- 3327012 TI - Geriatric assessment methods for clinical decisionmaking. PMID- 3327013 TI - [Pterins: pigments, cofactors and signal connections in cell interactions]. AB - Pteridines were originally described as pigments of insects and lower vertebrates. The electron-donating function of tetrahydrobiopterin for aromatic amino acid hydroxylation and thus, for neurotransmitter biosynthesis adduced the participation of unconjugated pterins in cellular metabolism. There has been increasing evidence moreover that they are signal molecules for intercellular recognition in primitive eucaryotes, as well as modifiers of signal polypeptides in higher vertebrates. PMID- 3327014 TI - [Pesticide residues in food plants: the role of plant metabolism]. AB - The plant metabolism of pesticides typically leads to various classes of persistent "soluble" and "insoluble" conjugates whose structures and modes of formation and storage have been characterized only in recent years. Pesticide risk assessment should include studies on animal bioavailability and toxicological properties of the conjugates. PMID- 3327016 TI - The sheep terminal nerve: coexistence of LHRH- and AChE-containing neurons. AB - The intracranial course of the terminal nerve was studied in the sheep. Luteinizing hormone-releasing hormone (LHRH) immunohistochemistry and acetylcholinesterase (AChE) activity detected histochemically revealed the existence of a major bundle of neural fibers coursing along the anterior cerebral artery, from the olfactory tubercle to the olfactory bulbs, at the surface of which the fibers spread out in a dense plexus, before reaching the cribiform plate. There were ganglia along the nerve, which contained at least two separate populations of identified cells: one possessing AChE activity and the other presenting LHRH immunoreactivity. PMID- 3327015 TI - [Calcium regulation of muscle contraction: the molecular regulation mechanisms of contracility]. AB - The role of calcium in muscle activation is described with particular emphasis on interactions occurring between the regulatory proteins troponin-C, troponin-I, actin and myosin. These interactions depend on calcium, but in turn they also influence the calcium binding to troponin-C. They may be affected by short "competitive" peptides whose sequences are similar to the amino-acid sequences on the protein-interaction sites. They may be also affected by certain drugs (cardiotonic calcium sensitizers) that influence the calcium sensitivity of myofilaments. PMID- 3327017 TI - Glycine potentiates N-methyl-D-aspartate-induced [3H]TCP binding to rat cortical membranes. AB - In extensively washed preparations of rat cortical membranes, N-methyl-D aspartate (NMDA) increases the specific binding of [3H]TCP by over 4-fold in a concentration dependent manner (EC50 = 3.1 microM). Glycine (1 microM) potentiates the maximal effect of NMDA by a factor of 1.7. The effect of glycine is concentration dependent (EC50 = 380 nM) and strychnine insensitive. These data are discussed with reference to the recently reported effects of glycine on the NMDA operated cation channel and the relationship between the PCP and NMDA receptors. PMID- 3327018 TI - The rapid reversibility of effects of changing lung volume on the clearance rate of inhaled 99Tcm-DTPA in man. AB - Five normal non-smoking subjects inhaled an aerosol of 99Tcm-DTPA in saline with a mass median aerodynamic diameter of 0.6 micron. The rate of clearance (k) of the inhaled 99Tcm-DTPA from lung to blood was measured using a gamma scintillation camera with computer data acquisition. During a single clearance study the subjects voluntarily breathed close to total lung capacity (TLC) and close to residual volume (RV). They breathed at one volume for 5 min, then at the opposite volume for 5 min and finally reverted to the original volume for 5 min with a 1 min pause between each manoeuvre. The order in which each subject performed these breathing patterns was randomized. Tidal volume, respiratory frequency and end expired volume were measured with a water spirometer. When they breathed close to TLC the rate of clearance increased (k = 4.62 +/- 1.03%/min) compared with breathing close to RV (k = 1.96 +/- 0.5%/min). This effect of changing volume was immediately reversible after adopting each new lung volume. There were no significant changes in tidal volume or respiratory frequency between each 5 min period. There was no significant difference between the clearance increased (k = 4.62 +/- 1.03%/min) compared with breathing close to RV (k = 1.96 +/- 0.5%/min). This effect of changing volume was immediately reversible after adopting immediate and reversible. PMID- 3327019 TI - [Results of using hyperbaric oxygenation as an immunodepressant agent in total keratoplasty in an experiment]. PMID- 3327020 TI - [Peripheral iridectomy in the treatment of closed-angle glaucoma]. PMID- 3327021 TI - [Remission in phase II and phase III studies: criteria and prerequisites]. AB - We identify factors of influence for the observed variability of published rates of remission and we derive from these findings prerequisites and criteria for the assessment of remission in cancer therapy. As a consequence we postulate a separate assessment of patients with measurable and with non-measurable disease and a complete documentation of those patient characteristics in order to compare rates of remission of different studies. Several methods for the determination of sample sizes in phase II and phase III clinical trials are presented and discussed. PMID- 3327022 TI - [Phase III study of chemotherapy in low-malignancy non-Hodgkin's lymphomas: comparison of vincristine-vindesine combination chemotherapy]. AB - In a phase-III study in non-Hodgkin's lymphoma of low malignancy we compared a combination therapy with vincristine (COP) with a vindesine combination (CEP). Remission rates, duration of remission and survival was favorable for the CEP combination without reaching the level of significance. The peripheral neurotoxicity of grade 2 and 3 according to WHO criteria was observed more frequently with vincristine. The vincristine-induced neurotoxicity in 6 patients was not impaired when a change was made to vindesine treatment. PMID- 3327023 TI - [Distant metastases of malignant thyroid cancer. A retrospective study of 892 cases]. AB - In 892 patients with thyroid carcinoma, distant metastases developed in 151 cases, and these were classified according to conventional pathohistological types and--in particular--to the incidence of surgically treatable solitary sites. The aim of the present study was also to investigate whether the histological diagnosis is of value in predicting the pattern of metastatic spread. Distant metastases of anaplastic carcinoma and sarcoma were found most frequently in the lungs (70 out of 81 patients, this is 86%), with 4 cases being solitary tumors. Metastatic spread into the skeleton, however, occurred rarely (14 out of 81 patients, 17.3%), when compared with differentiated carcinoma (64.8%). Moreover, with the exception of 1 case, metastatic growth was not solitary but involved more areas in bone. On the other hand, the well differentiated carcinoma displayed a greater predilection for the metastatic spread to the skeleton: 35 cases of bone involvement were identified in 54 patients with distant metastases (64.8%), and out of these cases, 10 metastases were solitary. Metastatic spread into the lungs occurred less often (30 of the 54 patients, 55.5%) and always displayed a diffuse pattern or involved multiple sites. In some cases, solitary metastases of different histological types were also identified in other organs. Our findings suggest that the pathohistological classification appears to be of use in guiding the clinical approach to a curative extirpation of distant solitary metastases in selected patients. PMID- 3327024 TI - [Concept of treatment of metastatic breast cancer outside university clinics: description of the method and evaluation of efficacy]. AB - It has been recognized during the past decade that it may be advantageous to develop complex strategies for treatment of metastatic breast cancer (MBC). In these strategies the type and efficacy of preceding therapies and the compliance of the patients have to be considered. Since about 80% of all patients with MBC are treated outside university hospitals it should be tested if a complex strategy for treatment of MBC can be realized in these institutions. The method was based on three principles: There was an exchange of data between participating institutions and study center after each visit of a patient. Second, there was one data sheet for admission of a patient to the study and fifteen sheets for follow-up documentation each with a different bottom line; in the bottom line of these sheets two therapies according to the strategy were proposed, one in case of 'no progression' and another in case of 'progression' of the disease. Third, a copy of completed sheets had to be returned to the study center; the study center provided the next sheet with the appropriate treatment recommendation. 335 evaluable patients were prospectively recruited from 27 participating institutions between January 1983 and December 1985. Based on the estimated incidence of MBC in the region, it was calculated that 45% of all MBC patients of the region had been admitted to the study. Only 27% of these patients were treated at the university hospital indicating that 85% of all MBC patients of the region were treated outside university hospitals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327025 TI - Retinal pigment epithelial cells produce fibronectin. AB - Antichick fibronectin antiserum, noncross-reactive to bovine fibronectin, was prepared to determine the production of fibronectin by cultured chick retinal pigment epithelial cells which were grown in the presence of fetal bovine serum. The typical fibrillary net pattern of fibronectin was observed by an indirect immunofluorescent technique when this specific antiserum reacted with cultured chick retinal pigment epithelial cells. Cultured chick retinal pigment epithelial cells were shown to produce fibronectin. PMID- 3327027 TI - Impingement syndrome in the absence of rotator cuff tear (stages 1 and 2). AB - Impingement syndrome affects a wide range of today's active population with various pathologies and presentations. Tendinitis can cause further subacromial loading, unless specific attention is directed at interrupting this disorder. Today's emphasis in high-risk populations, such as pitchers and swimmers, is on prophylaxis. Once symptoms occur, the majority can be successfully managed with nonoperative measures. Prolonged failure of conservative care prior to rotator cuff tear requires surgical decompression with predictable success in most. Results can be optimalized if strict attention is paid to patient selection, surgical technique, and a carefully supervised rehabilitation program following surgery. PMID- 3327026 TI - Ultrasonography of the shoulder. Static and dynamic imaging. AB - High-resolution, real-time ultrasonography is an effective diagnostic technique for evaluating rotator cuff movements and is useful in detecting aberrations that correlate with rotator cuff biomechanics and impingement syndrome. PMID- 3327028 TI - Ruptures of the rotator cuff. AB - Tears of the rotator cuff are a common entity. These tears frequently require surgical decompression and reconstruction. A number of options are available, depending on the quality of the tissues and one's ability to close the tear directly. Fortunately, in almost all cases direct closure of the cuff is possible after decompression. Early postoperative passive motion is useful in hastening recovery. Resistive exercises should be avoided early in the rehabilitation period. PMID- 3327029 TI - Anterior shoulder instability. AB - Current concepts for the diagnosis and treatment of anterior dislocation and subluxation, including classification of injuries, are presented. The pathophysiology, clinical and radiologic examination, and treatment protocols are discussed. PMID- 3327030 TI - Posterior shoulder instability. AB - The incidence, basic pathophysiology, and clinical and radiologic examination in posterior instability of the shoulder are discussed. Conservative treatment protocols and surgical procedures are presented. PMID- 3327031 TI - Displaced proximal humeral fractures. Selecting treatment, avoiding pitfalls. AB - This article, based on years of modified classification of displaced proximal humeral fractures, presents the treatment alternative for each type of injury and the problems to be avoided with each method. The authors recommend reduction and fixation in active patients with displaced proximal humeral fractures. Percutaneous pin fixation for two-part fractures, tension band fixation for three part fractures, and hemiarthroplasty for four-part fractures are advocated. PMID- 3327032 TI - Constrained arthroplasty of the shoulder. AB - Constrained replacement, like all prosthetic replacements, is constantly undergoing change and will improve as the current state of the art changes. It is not a standard, usual operation like unconstrained arthroplasty, and it should be reserved for the patient who requires arthroplasty and does not have a functional rotator cuff mechanism. If, in addition, the acromial fulcrum and loss of deltoid is present, then there is a greater reason for constrained replacement; it is a salvage procedure that is not as durable as the unconstrained device. Constrained arthroplasty has much merit if the risks and possible complications are well understood; however, pain relief and improved function will be lost if the device fails. The dislocation feature of the MRTS is desirable in order to minimize the risk of scapular fracture. Its disadvantage is that, with this complication, open operation is needed to reduce the assembly and insert new polyethylene components. The method of surface mounting of the metal glenoid component without removing the glenoid subchondral plate or cancellous bone of the vault is believed to lessen the risk of glenoid component loosening or pull-out. Finally, active function always depends upon residual deltoid muscle power. Thus, a poor or absent deltoid will only permit passive motion. PMID- 3327033 TI - [Traumatic avulsion of the skin]. PMID- 3327034 TI - [A method of crural amputation]. PMID- 3327036 TI - [Treatment of juvenile epiphysiolysis of the femur head (review of the literature)]. PMID- 3327035 TI - [Coating made of fetal membranes in the treatment of wounds (review of the literature)]. PMID- 3327037 TI - [Compression syndromes of the shoulder and their differential diagnosis]. AB - Compared to other painful conditions on the shoulder suprascapular nerve entrapment is an obscure and uncommon syndrome causing severe shoulder pain and disability, and is easily cured if only it is recognized. The condition was described by Thompson and Kopell in 1959, Schilf reported a case of isolated suprascapular entrapment in 1952. The nerve passes through the suprascapular notch, the roof of the notch is formed by the transverse scapular ligament. The shape of the suprascapular notch may be guilty for entrapment symptoms. Suprascapular nerve compression may result of acute trauma, of transmitted forces, fracture of collum scapulae, of kinking or traction of the nerve over the edge of the foramen, of sling effect, of compression by ganglia, or its cause may be idiopathic. The hallmark of suprascapular nerve entrapment is a deep and poorly delineated pain, localized to the posterior and lateral aspect of the shoulder. Atrophy and weakness of the supraspinatus and infraspinatus may be noted. Adduction of the extended arm across the body tenses the nerve, increasing the pain. Blocking the nerve by local anesthetic a dramatic, but not long lasting pain relief may be achieved. Electromyographically a decrease in the amplitude or marked polyphasicity of evoked potentials is significant as well as an increased latency time, indicating an impaired conductibility. A surgical release is indicated in case of constant pain and pathological changes of EMG-patterns. From a postero-superior approach decompression of the nerve is performed by simple removal of the transverse scapular ligament. PMID- 3327038 TI - [Unexplained pain conditions of the upper extremity]. AB - Diagnosis can be very difficult in the case of painful conditions of the upper extremity, since this is a region where the site of the changes and pathologic conditions precipitating or causing the pain is not always identical with the area where the pain is felt. This is particularly so in the case of pain resulting from vascular disease and irritation of peripheral nerves and in the thoracic outlet and inlet syndrome. Recent observations and studies suggest that this is extremely important for the etiology and pathogenesis of epicondylar periostitis and tendovaginitis, carpal tunnel syndrome, and some trophic conditions affecting the hand. Stenosis of the subclavian vein can be responsible for post-traumatic and postoperative edema of the hand and for similar changes whose "cause is unclear", and also for certain difficulties with wound healing. Preliminary experience suggests that Sudeck's dystrophy may be the most severe form of the thoracic outlet and inlet syndrome. Accordingly, transaxillary decompression of the neurovascular cord with upper thoracic sympathectomy can be recommended as a last resort for refractory Sudeck's dystrophy. The problem of epicondylitis of the lateral humerus is discussed in some detail, as is the pathogenesis of pain resulting from neuroma. PMID- 3327039 TI - [The ER-ICA, Lee and Taylor technics in breast carcinoma]. PMID- 3327040 TI - [Prognostic value of hormonal receptors determined by a histochemical method in operable carcinoma of the breast. Multicenter study]. PMID- 3327041 TI - [Various methods for the determination of receptors: how effective and how used in clinical medicine?]. PMID- 3327043 TI - [Use of receptor data in clinical oncology]. PMID- 3327042 TI - [Prognostic value of hormonal receptors]. PMID- 3327044 TI - [Presence of binding sites for steroid hormones in urothelial tumors]. PMID- 3327045 TI - [Immunoperoxidases in the study of hormone receptors in colorectal cancer]. PMID- 3327046 TI - [Carcinoma of the colon and rectum: comparison of grading, estrogen and progesterone receptor status and proliferative activity]. PMID- 3327047 TI - [Determination of estrogen receptors of breast carcinoma with the PAP method. Retrospective study from 1979 to 1985]. PMID- 3327048 TI - [Morphologic and immunohistochemical aspects of Barrett esophagus]. PMID- 3327049 TI - Juvenile hyaline fibromatosis. Case report and review of the literature. PMID- 3327050 TI - Osteogenic sarcoma symptomatic metastases presenting as obstruction to the right heart. Case report and review of the literature. PMID- 3327051 TI - Study of a possible induction of a production of anti-methotrexate antibody. PMID- 3327052 TI - Supraventricular and ventricular arrhythmias in the postoperative patients. PMID- 3327053 TI - [Neonatal oxygen therapy. Monitoring of PO2 by using capillary microsample]. AB - Capillary blood obtained from puncture of a warmed heel was tested for PO2 monitoring in management of 31 infants (1215-3920 g) with perinatal asphyxia and/or RDS. PO2 means during O2 administration were referred to mean values +/- I sigma for 108 normal term infants. All infants survived, with only a neurological complication due to a severe RDS with pneumothorax during CPAP treatment. We confirm the reliability of capillary microsampling collected blood for PO2 monitoring in RDS management too. PMID- 3327054 TI - [Usefulness of fructosamine determination in short-term monitoring of metabolic control in children with insulin-dependent diabetes mellitus at onset]. AB - The present study was undertaken to determine the clinical usefulness of fructosamine estimations in monitoring the short term changing in metabolic control in 5 newly diagnosed type 1 diabetic children (3 boys, 2 girls, aged 3-13 years). Mean glycaemic values, HbAlc (normal range: 4.77 +/- 0.67%), fructosamine (normal range: 2.65 +/- 0.65 mmol/l) were determined at the admission and after 1, 2, 3, 4 weeks. Normoglycaemia was achieved within 1 week (mean values: 232 +/- 107 mg% at admission; 98 +/- 39 mg% after 1 week of insulin therapy), HbAlc slightly decreased from 12 +/- 0.71 at admission to 9.90 +/- 1.81 after 4 weeks, but not reached normal values. Fructosamine decreased from 5.49 mmol/l to near normal values (3.02 +/- 0.67) after 4 weeks. The validity of the method was confirmed by the comparison of HbAlc and fructosamine in 22 stable long-standing diabetic children (r = 0.77, p less than 0.01). Compared with HbAlc, fructosamine appeared more useful in monitoring short term (3 weeks) changes in metabolic control. Additional advantages were lower cost and technical simplicity of measurement. PMID- 3327055 TI - [Immunofluorescence in the determination of gliadin antibodies in celiac disease]. AB - IgG gliadin antibodies (AGA-IgG) were detected by immunofluorescence in 78 celiac children diagnosed by jejunal biopsy. AGA-IgG were also detected in patients affected by other gastrointestinal disease, in patients with diabetes, in health children and in children with normal mucosa. AGA-IgG were found in 81% of celiac patients, while they were not detected in patients affected by other intestinal or extraintestinal diseases, neither in healthy controls. It is conclude that determination of AGA-IgG is a very specific and sensitive enough screening test before small intestinal biopsy. PMID- 3327057 TI - Endogenous opiates: 1986. AB - This is the ninth installment of our annual review of research involving the endogenous opiate peptides. It is restricted to the non-analgesic and behavioral studies of the opiate peptides published in 1986. The specific topics this year include stress; tolerance and dependence; eating; drinking; gastrointestinal, renal, and hepatic processes; mental illness; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; activity; sex, pregnancy, and development; and some other behaviors. PMID- 3327056 TI - [Iridocyclitis and juvenile rheumatoid arthritis]. AB - Iridocyclitis is a common complication of juvenile rheumatoid arthritis. It affects particularly female patients with mono-oligoarthritis. A positivity of ANA-test is usually observed, representing a marker for the disease. The course is chronic, leading potentially to scarring and blindness. The insidious onset, often not parallel to arthritis, requires careful ophthalmologic examination of all patients at risk, in order to achieve early diagnosis and treatment. PMID- 3327058 TI - [Pulmonary and respiratory syndromes. 1]. PMID- 3327059 TI - [Status of sonography in the diagnosis of Pancoast syndrome]. PMID- 3327060 TI - [Virulence of the microbial preparation Bactorodencide for various animal species]. AB - The virulence of the biological preparation for plant protection Bactorodencite is studied in 6 species of wild and domestic animals and game. Its high specificity concerning rodents is established at the highest rate in Ratus Norvegicus and inbred mice - C57 Black. Indocile to S. enteritidis var. issatschenko (active start of the Bactorodencite) are the grey pigeons, hens, ducks, pheasants, lambs and pigs. The time for clearing the organism of the indocile animals depends on the quantity (dose) absorbed bacteria, the specy of animals, and is not longer than 18-20 days. PMID- 3327061 TI - Role of specific cellular targets in the hematoporphyrin-sensitized photoinactivation of microbial cells. PMID- 3327062 TI - Phthalocyanine photosensitization for in vitro elimination of residual acute non lymphoblastic leukaemia: preliminary evaluation. PMID- 3327063 TI - Photodynamic therapy of head and neck squamous cell carcinoma: optical dosimetry and clinical trial. PMID- 3327064 TI - Passive immunization of fetal rats with antiserum to luteinizing hormone releasing hormone (LHRH) or transection of the central roots of the nervus terminalis does not affect rat pups' preference for home nest. AB - Luteinizing hormone-releasing hormone (LHRH) is found immunocytochemically in cell bodies and fibers of the nervus terminalis, a cranial nerve which courses from the nasal septum through the cribriform plate of the ethmoid bone (medial to the olfactory and vomeronasal nerves) and enters the forebrain, caudal to the olfactory bulbs. Immunoreactive LHRH is first detected in the nervus terminalis of the fetal rat at 15 days of gestation, preceding its detection by immunocytochemistry in any other area of the brain, including the median eminence, and preceding detection of immunoreactive luteinizing hormone (LH) in the anterior pituitary. During development of the rat fetus, the nervus terminalis is the principal source of LHRH in the nervous system from days 15 through 19 of a 21 day gestation period. We tested the notion that the LHRH system of the nervus terminalis is important for olfactory performance by examining the effects of administration of antisera to LHRH during fetal development (versus saline controls), or medial olfactory peduncle transections, in the neonatal rat, which would sever the central projections of the nervus terminalis (versus lateral peduncle transection, complete transection of the olfactory peduncles and the central nervus terminalis or controls) on preferences of rat pups for home nest. The hypothesis that LHRH is important for this chemosensory response was not confirmed. Neither antisera to LHRH nor medical olfactory peduncle transection disrupted preference for home shavings. Only complete olfactory peduncle transection had a significant effect compared to unoperated and sham-operated controls. PMID- 3327065 TI - [The journal function of Pielegniarka polska]. PMID- 3327067 TI - [Some considerations on "paternalism" and "self-determination" in psychiatric practice]. PMID- 3327066 TI - [Present trends in the diagnosis of chronic naso-paranasal sinus inflammation]. PMID- 3327068 TI - [Hermann Emminghaus--100 years of the psychopathology of childhood and adolescence]. AB - The centenary of Hermann Emminghaus's monograph "Die psychischen Storungen des Kindesalters" ("The Psychic Disorders of Childhood") gives occasion to appreciate the life and work of the founder of modern children and youth psychiatry. Children and youth psychiatry, in the G.D.R., operates on the principle of sub specialization out of its parent subjects. In this, Hermann Emminghaus's basic views, as expressed in his monograph of 1887, are confirmed. PMID- 3327070 TI - [Theodor Ziehen (12 November 1862-29 December 1950)--his life and work]. AB - Biography and scientific development of Theodor Ziehen as neurophysiologist, neuroanatomist, psychologist, psychiatrist, neurologist and philosopher are described. PMID- 3327069 TI - [Psychodynamic aspects of depression and suicidal behavior in childhood and adolescence--with reference to the monograph by Hermann Emminghaus 1887]. AB - The centenary of the first monograph on children psychiatry gives occasion to stress the topicality of a syndrome-oriented children and youth psychopathology, as well as the special importance of anxiety symptomatology as an index symptom of depressive interrelational disorders within the psycho-social field of experience during development. The paper discusses both multi-dimensional and psychodynamic approaches. PMID- 3327071 TI - [Brain structures related to the mechanisms of depression and the mechanisms of action of antidepressive drugs]. PMID- 3327072 TI - [Effect of lithium on mechanisms of membrane transport and adenyl cyclase activity]. PMID- 3327073 TI - The unknown Fechner. PMID- 3327074 TI - Outline of a new principle of mathematical psychology (1851). By Gustav Theodor Fechner (translation) PMID- 3327075 TI - Some thoughts on the psychophysical representation of memories (1882). By Gustav Theodor Fechner (translation) PMID- 3327076 TI - My own viewpoint on mental measurement (1887). By Gustav Theodor Fechner (translation) PMID- 3327078 TI - [Bacteriophages, lysogeny and its genetic determinism]. PMID- 3327077 TI - The methodological and statistical evaluation of medical tests: the dexamethasone suppression test in psychiatry. AB - Presented herein is a step-by-step discussion of the statistical evaluation of a medical test, using the literature concerning the DST to provide good and bad examples of its implementations. Specific topics of concern include: (1) conceptualization issues such as the definition of a test and its purpose; (2) implementation issues such as sampling and blindness; (3) analytic issues such as choice of statistical measures of quality; (4) issues of correct and realistic interpretation of results; and, finally (5) cost-benefit issues. PMID- 3327079 TI - Animal generation and the mechanical philosophy: some light on the role of biology in the scientific revolution. PMID- 3327080 TI - What counts as evidence or who was Franz Moewus and why was everybody saying such terrible things about him? PMID- 3327082 TI - Sociobiology and ethics. "Taking Darwin Seriously". By Michael Ruse. Essay review. PMID- 3327081 TI - Forgotten data on the introduction of aseptic techniques. PMID- 3327083 TI - [Life science and philosophy in the l7th and l8th centuries. "Metaphysics of the Embryo. Science of Life and Philosophy from Malpighi to Spallanzani (1672-1793)". By Walter Bernardi. Essay review]. PMID- 3327084 TI - [Physiology as pacesetter for surgery in the works of Theodor Kocher. "Nobel Prize Winner Theodor Kocher 1841-1917". By Ulrich Trohler. Essay review]. PMID- 3327085 TI - Evolutionary epistemology as a philosophy of nature. "What can we know?" By Gerhard Vollmer. Essay review. PMID- 3327086 TI - Quantum mechanical calculations of NMR chemical shifts in nucleic acids. PMID- 3327087 TI - Microscopic imaging of cells. PMID- 3327088 TI - [Evaluation of a computerized system for the analysis of urine]. AB - The computer's use permits an easy evaluation and a fast revision for urinalysis too. In the present experience, we report a study about the comparison among computerized data, the clinical requirement and the quality of urinalysis, sent to the laboratory of the Children's Hospital "Burlo Garofolo" of Trieste (Italy). PMID- 3327090 TI - [Ultrasound examinations in endocrine ophthalmopathy]. PMID- 3327089 TI - [Importance of the laboratory in optimizing anti-asthma therapy with theophylline]. AB - In relation to antiasthmatic treatment of hospitalized patients with theophyllines, results concerning: a) a retrospective analysis of plasma levels observed over a 18-month period; b) a pharmacokinetic study and consequent determination of an efficient individual posology are reported. On the 194 serum drug tests (each comprehensive of the trough and peak concentrations) evaluated, 58 (30%) entered the retrospective study, after screening by predetermined criteria. 96 out of 194 (49%) tests were eliminated because of inappropriate sample collection or irrational dosage regimen. The theophylline blood levels, distinguished by drug formulation and posology, were spread over very large ranges (coefficient of variation up to 88%, mean of 55%), so that many concentrations were subtherapeutic or potentially toxic. The kinetic study, undergone by 22 patients, was carried out by administering and intravenous test dose of aminophylline, followed by collection of blood samples at determined times. Elimination half-life, clearance and volume of distribution were then calculated by means of the plasma theophylline concentrations and subsequently an individual optimized dosage regimen (so as to keep the blood drug levels within the 8-16 mg.l-1 range) was determined. The considerable variability of elimination rate observed among patients (extreme values of half-life and clearance differ 10-fold) mainly account for the unforeseeability of plasma levels obtainable with a given posology. Even if the factors affecting the elimination rate of theophylline (i.e. cigarette smoking, obesity, congestive heart failure, chronic obstructive pulmonary disease, pneumonia) are taken into account, the blood concentrations are frequently unforeseeable. Therefore, the monitoring of plasma levels is necessary for every patient treated with theophyllines and a pharmacokinetic study is desirable in some cases. PMID- 3327092 TI - Detection of lymphocyte cytotoxicity in autoimmune thyroid disorders on porcine thyroid cell culture. PMID- 3327093 TI - Dot immunobinding assay for antibodies to TSH receptor. PMID- 3327091 TI - Ultrasound and CT-diagnostics of endocrine orbitopathy. PMID- 3327094 TI - Comparison of radioimmunoassay with enzyme-immunoassay and other methods for thyroid antimicrosomal antibodies determination. PMID- 3327096 TI - Histologic and cytologic problems of the diagnosis of thyroid cancer. PMID- 3327095 TI - The significance of estimating TSH-receptor-autoantibodies (TRAK-assay) for diagnostics of thyroid diseases. PMID- 3327097 TI - The thyroid carcinoma and malignancy in ultrasound and CT. PMID- 3327098 TI - Folding and association of proteins. PMID- 3327099 TI - Fluorescence energy transfer and membrane potential measurements monitor dynamic properties of cell membranes: a critical review. PMID- 3327100 TI - Genetics and biochemistry of the assembly of proteins into the outer membrane of E. coli. PMID- 3327102 TI - [Risks of recurrence in children with epilepsy after withdrawal of anticonvulsant drugs]. PMID- 3327101 TI - [Acute glomerulonephritis in children. Prospective study of clinical, histopathologic and immunologic aspects]. PMID- 3327103 TI - [Hereditary spherocytosis in the neonatal period]. PMID- 3327104 TI - [Comparative study of epidemiologic surveys on the occurrence of leprosy from 1980 to 1984 in the municipalities of 10 de Octubre and Arroyo Naranjo]. PMID- 3327105 TI - [Effect of the suppression of the popliteal ganglion in the reproduction of Mycobacterium leprae in the foot-pad of mice. Preliminary report]. PMID- 3327106 TI - [Cell-mediated immunity in patients with leprosy treated with rifampicin]. PMID- 3327107 TI - [Sites of outdoors posthematophagous rest of Anopheles (A.) crucians Wiedemann, 1828 (Diptera: Culicidae)]. PMID- 3327109 TI - [An epidemiologic group at high-risk. Cases of Plasmodium falciparum malaria, imported from the People's Republic of Angola, resistant to drugs. First report]. PMID- 3327108 TI - [Comparative study of the infestation of Romanomermis culicivorax (Ross and Smith, 1976), Rhabditida, Mermithidae in larvae of the mosquito Culex quinquefasciatus Say 1823 under laboratory conditions]. PMID- 3327110 TI - [50 anniversary of the founding of the Pedro Kouri Institute of Tropical Medicine]. PMID- 3327111 TI - [Various social characteristics of leprosy patients in Havana City]. PMID- 3327113 TI - [Hematophagous activity of Culicidae (Diptera: Culicidae) and Simuliidae (Diptera: Simuliidae) in the Isla de la Juventud. Preliminary study]. PMID- 3327112 TI - [Biological risk associated with in the field work: report of 2 cases of histoplasmosis]. PMID- 3327114 TI - [Dermatophytic flora in Cuban soils]. PMID- 3327115 TI - [Comparative study of lipid fractions of strains 220, 337 and 493 of Mycobacterium habana and strains W55, 1595 and 7729 of Mycobacterium simiae using the technics of thin layer chromatography and high performance liquid chromatography]. PMID- 3327117 TI - [Current status of Hartmann's operation]. PMID- 3327116 TI - [Usefulness of mechanical sutures in colorectal reconstruction after intervention by the Hartmann method]. PMID- 3327118 TI - [Hepatic metabolism of cholesterol, formation of biliary calculi and frequency of colorectal cancer]. PMID- 3327119 TI - [Epidemiology and clinical forms of presentation of celiac disease]. PMID- 3327120 TI - [Drug treatment of left ventricular insufficiency. Current aspects]. AB - The medical treatment of left ventricular failure classically relies upon the use of diuretics with or without digitalis. The recent arrival of vasodilators allows for both an improvement in the quality of life as well as a prolongation of survival for people in heart failure. The "new" positive inotropic agents which can be used orally in the longterm have not yet given the results which were anticipated. The prognosis of left ventricular failure remains poor, underlining the importance of preventive treatment and in the last resort the possibility of cardiac transplantation. PMID- 3327121 TI - Role of fluid replacement, increased oxygen availability by perfluorochemicals and enhanced RES function in the treatment of mesenteric occlusion shock. AB - Experiments were carried out on 183 rats to study the effect of a complex therapy for treatment of mesenteric shock. The superior mesenteric artery (SMA) was temporarily ligated for 90 min under ether anesthesia; this was followed by an analgesic treatment. After release of the ligated artery, fluid therapy was instituted by administering the equivalent of 7.5% of body weight of one of three different solutions: ringer lactate (RL), hydroxyethyl starch (HES) in RL, and perfluorochemicals (PFC, 4 g/kg b.wt. in RL with HES), the latter with the aim to improve the oxygen transport to the tissue. The same fluid therapy was carried out on rats pretreated with E. coli endotoxin. Endotoxin pretreatment was chosen to compensate the negative effect of PFC on the reticuloendothelial system (RES) as shown in previous studies. Survival time and survival rate were recorded as well as hematocrit values at different times before and after treatment. Experimental groups were: CONTROLS: (1) SMA occlusion without release; (2) 90-min occlusion without therapy. Treated animals: (3) RL therapy; (4) therapy with HES in RL; (5) therapy with PFC in RL and HES; (6), (7), and (8) identical therapies as Groups 3, 4, and 5, respectively, but with endotoxin pretreatment. Survival time increased to the same extent if HES or PFC were added to RL. There was a further increase both in survival times and rates with endotoxin pretreatment (Groups 6, 7, and 8 vs. Groups 3, 4, and 5). The highest survival time and rate were obtained in Group 8, which received PFC therapy with endotoxin pretreatment. There was a slight negative correlation between survival time and hematocrit values if all groups were considered together.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327122 TI - Principles of wound healing and tissue transfer techniques useful for genitourinary reconstructive surgery. PMID- 3327124 TI - Hypospadias. PMID- 3327123 TI - Application of tissue transfer techniques to the management of urethral structures. PMID- 3327125 TI - Operative procedures for epispadias and exstrophy of the bladder. PMID- 3327126 TI - Bent penis. PMID- 3327127 TI - [25 years of gerontology. A look backward and perspectives]. PMID- 3327128 TI - [Heinrich Meng, 1887-1972. Pioneer of mental hygiene in Switzerland]. PMID- 3327129 TI - [Preventive treatment in thromboembolic disease in surgical patients]. PMID- 3327130 TI - [Role of the fibrinolytic system in thrombosis]. PMID- 3327131 TI - [New thrombolytic agents: present and future]. PMID- 3327132 TI - [Thrombosis and hypercoagulable states]. PMID- 3327133 TI - [The bone bank of the University Clinic in Navarra]. AB - The Bone bank at the University Clinic is described along with its three units: Electrical freezer (-40 degrees). Liquid nitrogen freezer (-197 degrees). Temperature programmer descend. The first unit is used for the preservation of cancellous bone, for a limited lapse of time; the second unit is employed for preserving cortical grafts for an unlimited period. The third unit allows to control the temperature descend rate, in order to preserve the viability of chondrocytes in grafts including epiphyseal ends. Clinical applications of bone grafts are currently enlarging in areas such as tumour surgery, spine surgery and arthrodesis and reconstructive procedures of the hip joint. PMID- 3327134 TI - [Campylobacter pyloridis: the etiologic agent of gastritis and peptic ulcer?]. PMID- 3327135 TI - [Relapsing polychondritis. Aspects of the associated renal lesion]. PMID- 3327136 TI - [Experimental study regarding the persistence of the yeast Candida albicans in river water]. PMID- 3327137 TI - [Correlation between the concentration of secretory antibodies and the distribution of vaginal flora]. PMID- 3327140 TI - [Study of leptospirosis in our country, from the early beginnings to the present]. PMID- 3327139 TI - ["Influenza"--panic of the 1889 influenza epidemic. The medical mentality at the time]. PMID- 3327138 TI - [Epidemics and the Bran Pass. The anti-epidemic role of Bran]. PMID- 3327141 TI - [Pasteur and veterinary medicine]. PMID- 3327142 TI - Dunnifilaria meningica sp. n. (Filarioidea: Onchocercidae) from the central nervous system of the wood-rat (Neotoma micropus) in Mexico. AB - Dunnifilaria meningica sp. n. (Filarioidea: Onchocercidae) is described from the wood-rat, Neotoma micropus, trapped in Nuevo Leon State, Mexico. The adult worms are characteristically found in the subarachnoid spaces along the cerebellum and the medulla oblongata. The short, sheathed microfilariae are found in the peripheral blood. They do not show a periodicity. The adults are of small size (female worms are approximately 50 mm long, males about 25 mm). Female worms are didelphic. Male worms have subequal, dissimilar spicules and peri- and postanal papillae. This is the third species of the genus Dunnifilaria. It differs from the other species in its habitat in the host, the size of the body, the female tail length, the number and arrangement of the caudal papillae. PMID- 3327144 TI - Risk in a national malaria control programme in Mali: underdosage of antimalarials. AB - In order to be able to start malaria control activities based on the systematic treatment of episodes of fever in the context of a primary health care programme in the Selingue dam area, it was necessary to determine the sensibility of P. falciparum to chloroquine given at 25 mg/kg body weight for 3 days. The WHO 7-day test was adopted and administered to schoolchildren aged 7 to 14 years. Out of a total of 259 children screened, the parasitological examination of the thick blood film revealed the presence of hematozoids in 107 children (i.e. a parasite index of 41.3%). Of the 107,59 had parasitaemia appropriate for the in vivo test, but only 43 could be observed till the end of the 7-day test period. The results of the in vivo study indicated a single case where no elimination of the parasites was observed until day 6. The remaining 42 cases became negative between day 3 and day 4. The mean elimination time for the parasite in our study was 3.6 days. The prolonged parasite clearance rate was explained by the fact that the chloroquine tablets contained only 65% of the declared contents of chloroquine base. PMID- 3327143 TI - Neuraminidase fluorescence test for the differentiation of Trypanosoma cruzi and Trypanosoma rangeli. AB - The cell free supernatants of 13 stocks of Trypanosoma rangeli/T. rangeli-like, 50 stocks of T. cruzi/T. cruzi-like and 3 stocks of T. conorhini grown in culture were examined by using the 2-(4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid) test. It could be demonstrated that only the supernatants of the T. rangeli/T. rangeli-like stocks showed a white-yellow fluorescence under UV light. In contrast, the cell free supernatants of the T. cruzi/T. cruzi-like and T. conorhini stocks showed an ash-grey colour under UV light undistinguishable from that of the control reactions. The 4-MUAc test could be a method of choice for the routine detection of T. rangeli/T. rangeli-like flagellates in culture. PMID- 3327145 TI - Effects of the two new anthelmintic agents CGP 6140 and CGP 20376 on adult Paragonimus uterobilateralis in the experimental host Sigmodon hispidus. AB - The new compounds CGP 6140 and CGP 20376 were tested for their anthelmintic activity against adult Paragonimus uterobilateralis in experimentally infected Sigmodon hispidus. Both drugs were effective at a dosage of 2 x 100 mg/kg b.w. given orally with an interval of six hours between the doses. This regimen killed 80% of the flukes collected on Days 7 and 11 after treatment with CGP 6140 and 100% of the flukes collected on Days 5, 7, and 11 after therapy with CGP 20376. Both compounds showed no effect at single doses of 25, 50 and 100 mg/kg or with 12.5 and 25 mg/kg/day given on four consecutive days. PMID- 3327146 TI - [Habitual shoulder dislocation--its surgical treatment]. PMID- 3327147 TI - Cytotolerance of new dental alloys with a low gold content. PMID- 3327148 TI - Changing pattern of neonatal meningitis in Sweden. A comparative study 1976 vs. 1983. AB - A nationwide retrospective epidemiological survey of neonatal meningitis in Sweden was performed in order to estimate possible changes in incidence, etiology and mortality. The total number of newborns with meningitis was 137 and 40 (29%) were preterm (less than 37 gestational weeks) infants and 27 of these preterm boys (20%). Meningitis from group B streptococci and Escherichia coli, the two major causative organisms in 1976, had decreased markedly in 1983. The identification rate of viral origin was more frequent during 1983 compared to 1976. The total incidence of meningitis was 8.9/10,000 livebirths in 1983 vs. 5.6/10,000 in 1976 but the rate of verified bacterial meningitis had decreased from 3.6/10,000 (1976) to 1.9/10,000 (1983). The total outcome was improved significantly since the combined mortality and handicap rates decreased from 34% in 1976 to 15% in 1983. PMID- 3327149 TI - Twice-a-day regimen of erythromycin base is effective in the treatment of acute streptococcal tonsillitis. AB - A multicenter clinical trial on the efficacy and safety of a twice-a-day administration of erythromycin base was performed on 261 adolescent or adult patients with acute tonsillitis. The patients were randomized for each doctor separately into q.i.d. (4 x 250 mg) and b.i.d. (2 x 500 mg) groups. Throat swabs were cultured for group A beta-haemolytic streptococci before the treatment and, in positive cases (100 patients), 2-3 days after completing the treatment of at least 7 days. No significant difference in the efficacy between the two regimens was observed as judged by clinical evaluation or bacteriological examination. About 90% of patients were completely healed by both criteria in both treatment groups. Side-effects were reported in 40 and 44% respectively, in the treatment groups. However, only 9/244 (3.7%) had to stop the treatment because of side effects. Six of these belonged to the b.i.d. group and 3 to the q.i.d. group. This difference is not statistically significant (p greater than or equal to 0.05). Our results suggest that twice-a-day regimen of erythromycin base is an effective and well-tolerated treatment of streptococcal tonsillitis. PMID- 3327150 TI - Failure of a single dose of 100 mg ofloxacin in lower urinary tract infections in females. AB - A single dose of 100 mg ofloxacin was compared with a multiple dose of cotrimoxazole in lower urinary tract infections in 137 women. The elimination rate was significantly lower in the single dose treated group of patients in spite of all strains being in vitro susceptible in this group. PMID- 3327151 TI - Prefertile vas lesion as a cause of sperm antibody formation: an experimental and clinical study. AB - It is well known that vasectomy in adult men can induce formation of sperm antibody (SPA) and that the presence of such antibodies can be correlated to decreased fertility. Operations close to the vas, e.g. herniorrhaphy, are common in childhood, implying a potential risk of a vas lesion. However, very little is known about the consequences of a vas lesion at prefertile age with respect to SPA formation in adulthood. The aim of this study was to determine whether a vas lesion at prefertile age can induce SPA formation after puberty; if so, is it possible to prevent the occurrence of such antibodies by microsurgical reconstruction of the vas lumen before puberty? Prefertile rats (aged 3-6 weeks) were subjected to uni- and bilateral vasectomy, uni- and bilateral crush injury to the vas and bilateral injury to the ductal artery. SPA could be demonstrated in all groups of animals at the age of 18-20 weeks by means of indirect immunofluorescence technique. Prefertile uni- and bilateral vasectomy caused SPA formation to the same extent as did adult bilateral vasectomy (90% of the animals SPA-positive), whereas the prefertile vas appeared more sensitive to crush injury than the adult vas (70% and 11% SPA-positive, respectively). In rats subjected to vasectomy at the age of 3-4 weeks, it was possible to prevent SPA formation in adulthood by vas reconstruction before puberty. It was further shown that the vas repair did not have to be performed immediately after injury but could be delayed several weeks postvasectomy provided it was still performed before puberty. By using a tissue glueing agent (fibrin glue) it was found possible to improve the anastomosis healing in vasovasostomies. This was probably due to the fact that the fibrin glue minimises sperm leakage at the site of anastomosis in animals with an ongoing sperm flow through the vas at the time of vasovasostomy procedure. With this vasovasostomy technique, it was also possible to delay the vas reconstruction after prefertile vasectomy until puberty, still preventing the formation of SPA. The clinical implications of these experimental findings were underlined by the findings in a review of 31 postpubertal boys (mean age 17 years) operated upon for inguinal hernia in childhood. In this group, there was 100% accordance between the occurrence of SPA in the blood and vas obstruction. The findings in this clinical study further indicated that there may be a significant risk of acquiring an accidental, unknown vas lesion during herniorrhaphy in childhood.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327152 TI - The surgical treatment of acute facial burns. AB - Over a five-year period selected patients with acute facial burns have been treated with early excision and skin grafting. Guidelines on the experience gained are outlined. On admission a tentative diagnosis of the depth of the burn was made and saline dressings were applied. When the patient was considered to be out of immediate danger the wounds were re-examined under anaesthesia following surgical cleaning. Deep dermal and subdermal burns of the face in patients without potentially fatal injuries were tangentially excised (or were subjected to dermabrasion) and covered with skin grafts within the first three days. Deep dermal and subdermal burns combined with potentially fatal injuries were treated conservatively. Early excision and skin grafting performed under optimum conditions give excellent functional and good aesthetic results. PMID- 3327153 TI - The treatment of deep dermal burns by abrasion. AB - Deep dermal burns usually heal by a combination of epithelialisation and granulation tissue formation, and may form hypertrophic scars. Sometimes, however, they heal spontaneously and early with no hypertrophy. Early tangential excision and grafting is practised by many surgeons for these burn wounds, but, because of the problems of diagnosis and therefore the risks of unnecessary surgery, we have practised a policy of abrasion of burn wounds unhealed at two weeks after injury. The wounds were over-grafted or not depending on the appearance of the remaining dermis. Healing was generally rapid. Long term results show good scar formation with few problems from scar hypertrophy or contracture. PMID- 3327154 TI - The grafting of burns with cultured epidermis as autografts in man. Two case reports. AB - In two patients full-thickness burns were grafted with cultured autologous epidermis obtained using the technique described by H. Green. The grafts only took partially but produced satisfactory covering. Better efficiency and more information about the long-term characteristics of the resulting skin are necessary before routine use can be recommended. PMID- 3327156 TI - Management of fingernail deformities after thermal injury. AB - Fingernail deformities after thermal injury can be very disfiguring and troublesome. The fingernails may be discoloured, cleft or vertically deviated. From the pathophysiology of the nail growth in general, the specific features of the nail deformities after deep burn can be deduced, as can guidelines for the treatment. Over a two-year period, 153 patients with burned hands were treated in the Groningen Burn Centre. Seven of these patients developed abnormal quality and growth pattern of the fingernails. In two patients an effort was made to correct the deformity by incising the dorsal skin at the base of the nail fold, reflecting the nail fold and covering the acquired defect with a full thickness skin graft. Although the patients were satisfied with the results achieved, one year after the operation little or no improvement in the nail growth was found. A cautious policy should be followed in correcting these deformities, since dislocation of the eponychium together with damage to the nail matrix and the nail bed play a complex role in the process of deformation. PMID- 3327155 TI - Fixation of skin transplants in burns with SurfaSoft and staples. An analysis of the results. AB - The use of SurfaSoft and staples enables a rapid and adequate fixation of (meshed) skin grafts, even when large wounds and anatomically difficult areas are involved. The smooth, porous and transparent structure of SurfaSoft makes frequent inspection of the transplanted skin possible and allows dressing changes to be carried out from the first day after operation onwards. Analysis of 232 skin transplantations shows that on a surgical wound bed the mean take rate is 71% when full sheet or meshed transplants are used. A mean take rate of 96% can be achieved when expanded autograft and specially prepared allografts are used together for covering large wound areas. Transplantation of meshed skin on a granulating wound surface results in a mean take rate of 82%. PMID- 3327157 TI - Resurfacing full thickness burns of scalp: 'the cross-word technique'. Practical note. AB - A technique for the closure of extensive scalp defects resulting from burns is described which is particularly suitable for elderly subjects not able to withstand extensive surgical treatment. This technique is safe, swift and effective for cases of extensive exposure of the bony outer table of the skull devoid of periosteum following trauma. PMID- 3327158 TI - In vitro suppression of the epidermal Langerhans' cells in necro split skin. AB - The effect of ultraviolet light B irradiation and glucocorticosteroid incubation on the epidermal Langerhans' cell density and tissue viability was investigated, in vitro, on human thin necro split skin. PMID- 3327159 TI - Ceftazidime treatment in severe burns. Serious infections in patients with severe burns treated with ceftazidime. AB - In combination with active surgical and general management, ceftazidime is a useful antibiotic for the treatment of Gram negative septic complications in patients with severe burn wounds. Against S. aureus, however, ceftazidime is not the therapy of choice. PMID- 3327160 TI - HydroColloid dressing (Duoderm) for the treatment of superficial and deep partial thickness burns. AB - HydroColloid Dressing (Duoderm, HCD) is a new kind of dressing, based on the fact that occlusion can provide an optimum wound environment for quick re epithelialization. Seventy patients with superficial and deep partial thickness burns of up to 7% TBSA were treated with HCD. In 16 patients a second burned area, similar in size and depth of the burn treated with HCD, was treated with human allografts or silversulfadiazine (SSD). Five patients with very small full thickness burns were also treated with HCD. In three patients (4.5%) the treatment with HCD had to be discontinued before total re-epithelialization had occurred, for various reasons. Statistically, HCD provided faster re epithelialization than allografts or SSD. The cosmetic and functional results were excellent. After six months only one patient was found to have a small area of hypertrophy. In this study HCD was found to be a very good dressing for the treatment of smaller partial thickness burns. PMID- 3327161 TI - Immunity of the burned patient. An overview. AB - The study of mortality in severe burns shows very clearly that most patients die because of septic problems. Surgery and intensive care in burn patients are actually well established, but the fight against infection and septicemia is still difficult. The risk arises due to poor host defence, leading to an unfair struggle and very often ending in death. Today it has become necessary for every burn surgeon and plastic surgeon to understand why this immune depression occurs and how it can be prevented or treated. PMID- 3327162 TI - The continuing enigma of sudden infant death 1882-91--1977-86. PMID- 3327163 TI - Measles and human experience. PMID- 3327164 TI - 50th anniversary of the opening of Tennent Institute of Ophthalmology, University of Glasgow. PMID- 3327166 TI - Choice of NSAID: safety profile. PMID- 3327165 TI - Perthshire pioneer of anti-inflammatory agents (Thomas John Maclagan). AB - The achievements of Thomas John Maclagan (1838-1903) include the first specific use of salicin to cure acute articular rheumatism. He began salicin treatment in 1874 in Dundee, where he was a medical practitioner from 1869 to 1879. Maclagan was also the resident medical superintendent at Dundee Royal Infirmary from 1864 1866, where he was the first in Scotland to make investigative use of the clinical thermometer during the fever epidemics. From 1879-1903 he maintained a fashionable practice in London. His contributions to medicine and in particular to the development of aspirin, once ranked as equivalent to the achievements of Lister and Simpson, have now largely been forgotten. This account is a tribute to a life rich in individual endeavour, observation and effort before the "teamwork" era began. PMID- 3327167 TI - Current surgical strategies in ovarian carcinoma--a review. PMID- 3327168 TI - Skin immunofluorescence patterns in SLE patients in Singapore. PMID- 3327169 TI - Neonatal hypoglycemia due to nesidioblastosis--a case report. PMID- 3327170 TI - [History of the prevention of alcoholism in Russia (medical literature, 1800 1860)]. PMID- 3327171 TI - [Role of M.V. Lomonosov in the development of medical and health services]. PMID- 3327172 TI - Thoracic facetectomy and bone grafting in the surgical treatment of adult idiopathic scoliosis. AB - A retrospective study of adult patients with surgically treated idiopathic scoliosis was carried out to determine the importance of thoracic facetectomy and bone grafting. The results indicate that failure to excise and bone graft the thoracic facets was not associated with a significant impairment of initial correction or loss of correction after a mean follow-up of 2 years. The incidence of pseudarthrosis was comparable to other series. It also was established that the use of Bobechko hooks without postoperative bracing gave satisfactory results. PMID- 3327173 TI - The vertebral canal: I. Nutrition and development, an archaeological study. AB - The lumbar vertebral canal was measured in adult spines from two archaeological populations, and was compared with four physiological stress indicators, (cribra orbitalia, porotic hyperostosis, dental hypoplasia and Harris lines). The stature of 38 juvenile skeletons and their canal size were compared with those of the adults. By 4 years of age the midsagittal diameter and the area of the vertebral canal was fully mature and the mean interpedicular diameter 87% of adult size. There was a differential pattern of growth, with the proximal spine maturing first. The trefoil shape was not seen at L5 before puberty. Dental hypoplasia correlated with a small interpedicular diameter at L1, L2 and L3, and Harris lines with a small midsagittal diameter at L1, L3 and L5, a small area at L5 and a more trefoil canal at L4 and L5. There is evidence that adverse environmental factors are associated with the development of spinal stenosis. PMID- 3327174 TI - Monostotic fibrous dysplasia of the thoracic spine. PMID- 3327175 TI - Annual Statistical Supplement, 1987. PMID- 3327176 TI - [Problem-oriented teaching in the study of internal diseases]. PMID- 3327177 TI - [Blood insulinase activity in patients with diabetes mellitus]. AB - An original method was used for a study of blood insulinase activity in patients with type I (insulin-dependent) diabetes mellitus which was decreased as compared to that in healthy persons and in persons with disturbed glucose tolerance. A GTT caused no significant variations of this index. Relations between lowered blood capability to degenerate insulin in diabetes mellitus and a rise of antiinsulinase activity of the plasma with preserved normal insulinase activity of erythrocytic hemolysate were established. PMID- 3327178 TI - [Excess body mass, its fatty and muscular components in the diagnosis of primary degrees of alimentary obesity in women]. AB - In 235 women with excess body mass from 10 to 49% the fatty layer thickness was measured using a ut-40stsp T-40CIIII ultrasonic adipometer, and the fat and muscular mass of the body was determined on the basis of Ya. Mateika's formula. The comparison of values of the excess body mass index and the content of the adipose and muscular tissue revealed its limited informative value in the assessment of a degree of adipopexis in women with primary degrees of obesity. The content of the studied components and a value of the musculoadipose index made it possible to distinguish the imbalance (in 87.2% of the cases) and balance (in 12.8% of the cases) types of obesity. In the first type an increase in the adipose tissue is accompanied by a decrease in the muscular component whereas in the second one both components are equally on the increase. PMID- 3327179 TI - [Main indices of blood lipid composition in elderly persons and centenarians]. PMID- 3327180 TI - [Cellular aspects of immuno-inflammatory involvement of the kidneys]. PMID- 3327182 TI - [Diabetes mellitus: prospects for therapy and the prevention of late complications]. PMID- 3327181 TI - [Use of high-purity insulins in the treatment of patients with diabetes mellitus]. AB - A total of 43 patients aged 16-62 with moderately severe and severe type I diabetes mellitus of 2-27 years duration were observed. The patients were admitted to hospital with decompensation of metabolic processes. In order to achieve compensation monocomponent insulins were administered in an individual dose depending on the levels of glycemia and glucosuria and a scheme of drug administration (2 times continuously, i.v. using the Biostator apparatus). The duration of therapy was 4 months. A hypoglycemic effect in relation to immunological and hemorheological indices was assessed. A hypoglycemic effect was noted in all the patients. A positive effect of high-purity insulins on immunological and hemorheological indices was revealed. These insulins can be used for prevention of diabetic angiopathies. PMID- 3327184 TI - [Application of echography to the diagnosis of chromaffinomas of extra-adrenal localization]. AB - Sixty-one patients with chromaffinoma were examined by echography. Of these, 6 patients (9.8%) had extraadrenal tumors. Application of echography permitted a correct topical diagnosis to be made in 5 patients. In 2 persons, the tumor was located in Zuckerkandl's fascia, in 2 in the paraaortal ganglia at the level of the splenic vein and the left hilus renalis, and in 1 patient, it was located in the urinary bladder. In one of the cases, no chromaffinoma was found. Since the majority of extraadrenal chromaffinomas (96%) are located in the retroperitoneal space echography can successfully be used for diagnosing such tumors with the exception of intrathoracic tumors which cannot be visualized in connection with the presence of air in the lungs. In such cases use should be made of computer aided tomography. PMID- 3327183 TI - [Effect of corinfar on the course of angina pectoris and indices of carbohydrate metabolism in relation to the type of glucose tolerance]. AB - Nifedipine influence on a clinical course of angina pectoris, some indices of hemodynamics, glucose and insulin was studied in 39 male patients suffering from coronary heart disease (CHD) with different glucose tolerance. In CHD patients with normal glucose tolerance (NGT) nifedipine therapy did not cause any considerable changes in the blood levels of glucose and insulin whereas in patients with lowered glucose tolerance (LGT) a hypoglycemic effect of the drug and an increase in the level of insulin were noted during therapy. An increase in physical exercise tolerance, a decrease in the frequency of anginal attacks, and a decrease in the number of nitroglycerin tablets administered by CHD patients with LGT per week were significant. The study showed that nifedipine was indicated for CHD patients with LGT. PMID- 3327185 TI - [Pathophysiological features of arterial hypertension in chronic nephritis]. AB - The activity of the renin-angiotensin-aldosterone system (RAAS), excretion of renal prostaglandins, renal hemodynamics, water-electrolyte balance were studied in 110 patients with chronic nephritis with arterial hypertension: 47 with hypertonic nephritis and 63 patients at the stage of renal insufficiency. Some investigations, the results of data processing, an analysis of the results of cross-group comparative studies, and the use of captopril (a drug that inhibits the activity of angiotensin-converting enzymes) confirmed the RAAS involvement in the pathogenesis of arterial hypertension in nephritides. Pathophysiological features of arterial hypertension in nephritides are the following: disturbances of physiological interrelationships between renin plasma activity and the state of water-electrolyte balance; hyperaldosteronism and depression of renal prostaglandin synthesis revealed both in unchanged and lowered renal function. The peculiarity of arterial hypertension at the stage of marked renal insufficiency is invariability of renin production resulting from structural reserves of the renal juxtaglomerular apparatus. PMID- 3327186 TI - [New goals in the teaching of curriculum internal diseases (on 80th birthday of Z. A. Bondar')]. PMID- 3327187 TI - [Incidence, significance and epidemiology of drug side effects]. PMID- 3327188 TI - [Hematologic side effects of drugs]. PMID- 3327189 TI - [Cardiovascular side effects of drugs]. PMID- 3327190 TI - [Gastrointestinal and hepatic side effects of drugs]. PMID- 3327191 TI - Two hundred years of digitalis treatment: 1785-1985. PMID- 3327192 TI - [Extraction of drugs by dialysis]. PMID- 3327193 TI - [Cardiovascular manifestations in acute poisoning by antidepressive agents. Discussion and review of the literature]. PMID- 3327194 TI - [Reye's syndrome]. AB - Reye's syndrome, characterized by acute encephalopathy and fatty degeneration of the viscera with hepatic failure, is a life-threatening illness that affects children of all ages. Although Reye's syndrome has been investigated extensively, its etiology and pathogenesis remain obscure. Metabolic pathophysiology appears to include a process affecting liver mitochondria. Recently disturbances in fatty acid oxidation have been described with a similar clinical picture. The cause of these events is presumably related to triggering viral illnesses, in ways that are unclear. Since prompt treatment might provide a better chance for recovery, early diagnosis is important. PMID- 3327195 TI - [Prognosis in the cri-du-chat syndrome]. AB - Cri-du-chat syndrome (5p-) is one of the most frequently occurring chromosomal deletion syndromes in man. Clinical findings have been described extensively in literature, but documentation of the patients' mental development has been poor. Recently the clinical heterogeneity and variance in psychomotor development was studied in a large series of patients. Review of the literature revealed that some 15% of the cases were found to be familial, there appears to be a slight correlation between karyotype and phenotype and the positive effects of early stimulation programs on the patients' prognosis is pointed out. Some 60% of the patients need regular medical care and nearly all are mentally retarded. However a wide spectrum of developmental abilities is displayed and a number of patients can be reared at home for several years. Life expectancy depends on the number and severity of birth defects. PMID- 3327196 TI - [Diagnosis of liver diseases in dogs, cats and horses]. AB - Clinical symptoms of hepatopathies are not specific and must be verified by further investigation. Laboratory diagnosis is a very useful method to decide if liver disease is present or not. In individual cases laboratory methods can give hints as to the aetiology of the illness. If necessary, biopsy, angiography or/and cholecystography can be carried out for further clarification of the diagnosis. PMID- 3327197 TI - [Stomach torsion in swine]. AB - Sudden death in mature sows due to torsion of abdominal organs (stomach, spleen, liver) is described. Hepatic torsion is seen only separately, but gastric torsion and torsion of spleen appear by themselves as well as in combination with each other. Often no clinical symptoms are observed. Acute cardiovascular failure is responsible for death in these sows. Authors unanimously report on feeding as a possible aetiological factor. Both the composition and technique of feeding should therefore be examined in problematic live stock. Excitement and excessive movements before and during feeding as well as the rapid intake of large amounts of water and feed seem to predispose to the development of gastric dilatation or torsion in sows. Suitable prophylactic measures should be taken. PMID- 3327198 TI - [Injection technics for birds]. AB - In view of numerous legal cases of recourse on the basis of injections incorrectly carried out in birds, a description of the most important injection techniques was compiled with reference to existing literature on this subject. Intramuscular and subcutaneous injections are preferable methods of parenteral application. Intracutaneous application and its indication are briefly mentioned. Intravenous injection, blood sampling as well as different methods of euthanasia are described as well. PMID- 3327199 TI - [Anesthesia in birds]. AB - Anaesthesia in birds is ordered by law and is also necessary for various operations and manipulations. Anaesthesia by injection of Ketamin, which in special cases may be combined with Diazepam, has been found useful. Anaesthesia by inhalation with Halothan, Methoxyfluran or Isofluran is the most careful method. Local anaesthesia has few indications. PMID- 3327201 TI - Surgical correction of astigmatism. PMID- 3327200 TI - [Proteases and protease inhibitors of possible clinical relevance in COPD of horses]. AB - The importance of proteases and protease inhibitors for the pathogenesis of pulmonary emphysema and chronic bronchitis of the horse is described. Endogenous elastases from neutrophil granulocytes and macrophages, which probably provoke emphysema in the human being, are not relevant in horse emphysema. Exogenous elastases from different species of streptomyces may be responsible for emphysema generation in this species. Part of the exogenous elastases are poorly or not inhibited at all by the equine blood protease inhibitors especially by alpha 1 protease inhibitors. A disorder similar to genetic alpha 1-protease inhibitor deficiency in the human being could not be found in the horse. Proteases and protease inhibitors are probably also relevant for the pathogenesis of chronic bronchitis. Neutral proteases from neutrophil granulocytes may be relevant as initiators or amplifiers of an inflammation in the human being and in the horse. Under physiological conditions the proteases are controlled by the secretory protease inhibitor called HUSI-1 in the human being. In contrast, the horse lacks a protease inhibitor proper to secretion in its respiratory ducts. Protease activity, which correlates with the degree of the COPD, was detected in equine inflamed tracheobronchial secretions. This finding is useful in diagnostic evaluation of the individual disease. PMID- 3327202 TI - Refractive errors encountered with the triple procedure. PMID- 3327203 TI - Pathologic findings in cases of refractive corneal surgery. PMID- 3327204 TI - Triple procedure: comparison with standard extracapsular technique. PMID- 3327205 TI - Cystoid macular edema in keratoplasty. PMID- 3327207 TI - Prevention and correction of astigmatism: intraocular lens implants. PMID- 3327206 TI - Surgical correction of hyperopia and aphakia. PMID- 3327208 TI - Technical aspects; histopathology; surgical alternatives. PMID- 3327209 TI - Current concepts in extended wear. PMID- 3327211 TI - Variables in radial keratotomy. PMID- 3327210 TI - Structural considerations in refractive surgery. PMID- 3327212 TI - [Fluorescence cytochemistry of nucleic acids. The current status and outlook: on the 35th anniversary of the method]. AB - Most important fields of the fluorescence cytochemistry of nucleic acids are reviewed, special attention being paid to the following aspects of the problem: physicochemical basis of different methods of staining; new methods of cell analysis, including flow cytometry; functional studies, i.e. the use of fluorescence approaches to obtain information about the functional state of individual cells and cell aggregates. PMID- 3327213 TI - [Characteristics of the ultrastructural organization of the nuclei of somatic cell hybrids]. AB - A study was made of the ultrastructure of cell nuclei of two types of hybrid clones obtained from the fusion of Chinese hamster with human skin fibroblasts, and from that of mouse hepatoma cells with mink fibroblasts. In cell nuclei of the eight hybrid clones deep invaginations of the inner membrane, not characteristic of the parent cells, were revealed. Analysis of serial sections, and application of electron microscopic radioautography and histochemistry have suggested that these structures are associated with the nuclear envelope which is necessary for regulating the superfluous chromosome localization in the hybrid nucleus. PMID- 3327214 TI - [A method of intestinal "end-to-end" anastomosis]. PMID- 3327215 TI - [Modified jejunostomy in cancer of the stomach]. PMID- 3327217 TI - [Acute acalculous cholecystitis]. PMID- 3327216 TI - [Suppurative and septic complications of acute pancreatitis]. PMID- 3327218 TI - [Stomach-draining operations in vagotomy for duodenal ulcer]. PMID- 3327219 TI - [Development of traumatology and orthopedics during the 70-year period of the Soviet rule]. AB - The article elucidates the development of soviet traumatology and orthopedy. There appeared institutes, chairs at medical institutes and institutes for advanced postgraduate training. A network of ambulatory medical institutions and hospitals has been created in rural regions and towns. Scientific societies and Journal "Orthopedy, Traumatology and Prostheses" have made great contribution in the development of traumatology and orthopedy. PMID- 3327220 TI - [Use of myocardial electric stimulation for the treatment of cardiac rhythm disorders]. AB - Under study were 3 kinds of national sutureless myocardial electrodes compared with sutured electrodes. Sutureless electrodes were simply and reliably implanted into the ventricles and right auricle of the heart, they had better biophysical properties than sutured electrodes. The application of sutureless electrodes and special elevator of the breast bone allows to decrease the duration and traumatism of operations of myocardial electrocardiostimulation, lethality can be reduced to 1%, the amount of hospital complications to 5%. PMID- 3327221 TI - [Use of computerized tomography and echography in the diagnosis and treatment of abscesses of the abdominal cavity and retroperitoneal space]. AB - An analysis of complex use of computer tomography and echography for diagnostics, aimed biopsy and following measures in 32 patients with foci of purulent infection in organs of the abdominal cavity and retroperitoneal space has been made. In 11 patients with small abscesses not more than 5 cm in diameter percutaneous aimed punctures of the pus cavity were fulfilled followed by the aspiration of the content and introduction of an antibiotic. In 21 patients percutaneous drains were introduced into the abscesses by Seldinger's method or through a trocar. Curative punctures and percutaneous drainage in 85.7% of the patients gave successful results. PMID- 3327222 TI - [Treatment of sequelae of hand and finger burns in children]. AB - An experience with the treatment of 228 children aged from 10 months to 14 years with postburn deformities of 305 hands has shown expediency of preoperative preparation in burn traumas older than 2 years. The take of the transplanted free skin flap on the hand was proved to be influenced by the degree of immobilization of the hand operated on and the transplanted graft, the efficiency of permanent anesthesia of the humeral plexus of the operated arm and by tissue therapy with the amnion suspension. PMID- 3327223 TI - [Semicircular acetabuloplasty in dysplasia of the acetabulum in children]. PMID- 3327224 TI - [A method of plastic surgery of the mandible using autotransplants]. PMID- 3327225 TI - [Kuibyshev Military Medical Academy]. PMID- 3327226 TI - [Activities of the military medical hospital commissions during World War II]. PMID- 3327227 TI - [Responsibility for assigned matters (Aleksandr Ivanovich Korovin)]. PMID- 3327228 TI - [The use of computer analysis of electroencephalograms in psychiatry]. PMID- 3327229 TI - [Training of military field surgeons for the Russian army]. PMID- 3327230 TI - [The medical service during the military reform and technical reconstruction of the Red Army]. PMID- 3327231 TI - Women and nutrition. PMID- 3327232 TI - Effects of total energy and individual nutrient intakes on energy balance. PMID- 3327233 TI - Phytate in foods. PMID- 3327234 TI - Nutrient utilization during pregnancy. PMID- 3327235 TI - Technical, ethical and ideological responsibilities in nutrition. PMID- 3327236 TI - The biochemical mechanism of brown fat thermogenesis. PMID- 3327237 TI - Traditional practices concerning feeding during and after diarrhoea (with special reference to acute dehydrating diarrhoea in young children). PMID- 3327238 TI - From analysis to reality: bioavailability in nutrition and toxicology--a misunderstood concept. PMID- 3327239 TI - Nutrition and growth. PMID- 3327240 TI - The state of food and nutrition in the Arabian Gulf countries. PMID- 3327241 TI - Perplexities and controversies on diet and dental caries. PMID- 3327242 TI - Iron deficiency in Africa. PMID- 3327243 TI - The role of zinc in human nutrition. PMID- 3327244 TI - Aluminum and tin. PMID- 3327245 TI - Digestibility of protein and bioavailability of amino acids in foods. Effects on protein quality assessment. PMID- 3327246 TI - Psycho-social studies of malnutrition in southern Africa. PMID- 3327248 TI - [Bacterial endocarditis--a review]. PMID- 3327247 TI - [Indications for splenectomy from the internal medicine-hematologic viewpoint]. PMID- 3327249 TI - [J.E. Purkyne in the early history of modern physiology and histology]. PMID- 3327250 TI - [Contributions to the controversy on the effect of coffee and tea consumption on the human body in medical and popular scientific literature of the 18th and 19th century]. PMID- 3327251 TI - [Significance of sports training in diabetes mellitus]. PMID- 3327252 TI - [Acknowledgement of Schneeberg lung disease as an occupational disease in the 1st occupational disease decree of 1925]. PMID- 3327253 TI - [The wolf, Canis lupus L., as a rabies vector in the 16th and 17th centuries]. PMID- 3327254 TI - [Health education aspects in the historical assessment of the Jewish day of rest]. PMID- 3327255 TI - [30-year existence of the Institute of General and Community Health of the Rostock Wilhelm-Pieck University]. PMID- 3327256 TI - [Metabolism of free fatty acids in fatty tissue]. AB - Hyperlipacidaemias play a role as etiological partial factor in the pathogenesis of various acute and chronic functional disturbances and are essentially the sequel of a disturbed metabolism of the free fatty acids of the fatty tissue. With regard to its clinical relevance a survey is given of the free fatty acid metabolism of the fatty tissue and its free fatty acid net balance as resultants from lipolysis and triglyceride synthesis is described. The author deals with the regulation of the lipolysis by cyclic mononucleotides, adenosine triphosphate, adenosine, fatty acids, ions, beta-hydroxybutyrate, lactate as well as hormones and finally with the control of the triglyceride synthesis. PMID- 3327258 TI - [The auxiliary transplantation of a portion of liver in an animal experiment]. AB - The authors inform about a model for auxiliary liver part transplantation in pig. Intra-abdominal narrowness which can lead to failure of the transplant can avoided by this model. In the transplant was carried out an extensive left resection with purse-string ligature of all visible vessels and cystic ducts. The resection surface is sealed by a tissue adhesive. An auxiliary transplanted part of the liver can also operate on a heterotopic location of the organism. PMID- 3327257 TI - [Berolina iubilans: Berlin physicians as Halle doctoral candidates (VI). Curt Schimmelbusch (1860-1895), Halle doctoral candidate of 1886]. AB - The history of asepsis is closely connected with the name of Curt Schimmelbusch. The physician who was awarded the doctor's degree in Halle in 1886 as co-worker of the histologist and pathologist Eberth at first dealt with research in the field of thrombosis. He became famous all over the world by his investigations concerning the development and scientific fundamentation of mechanical sterilisation methods which he performed under Ernst von Bergmann in Berlin. In this field the name of Curt Schimmelbusch is rooted in the special terminology. PMID- 3327260 TI - [Former dietary measures in dermatology--a historical review]. AB - A historical view will be given on forms of diet formerly used in dermatoses (especially psoriasis, tuberculosis, atopic dermatitis, acne, rosacea and seborrhoeal eczema). The use of raw food, milk, and fruit, abstinence diets and juice cures in dermatological therapy still remain just as questionable as the effects of acidified or alkalised forms of food. Their abundance and diversity leads to the assumption that it is clearly not so much the composition of food, but more in the change of food and the extensive natural state of the basic foodstuffs used, which play an essential role in the influence on the progress of dermatoses. PMID- 3327259 TI - [Basic research in ultrasound surgery. VII. Comparative animal experiments after intestinal anastomosis by suturing, ligament gluing with Fimomed and ultrasound sealing with ligament Fimomed]. AB - Animal experimental anastomoses in the small intestine of Mini-Lewe-pigs showed that even sufficient anastomoses free of stenosis can be obtained by using the sticking respectively the ultrasound sealing method. The foreign-body reaction in the surroundings of the suture was approximately equally strong as on the gluten. All animals did not show any specialty in the postoperative course. The use of butylcyanidacrylic is possible in the human intestine as also shown in the literature. The use is indicated if advantages are to be expected in face of a suture anastomosis in clinical sight. PMID- 3327261 TI - [Skin reactions to food and food constituents--allergic and pseudoallergic reactions]. AB - Which skin reactions, with allergic or pseudo-allergic mechanism, are actuated by food? Contact urticaria or "forme-fruste-anaphylaxis" is the most common. Tests, using purchasable allergen extracts, mostly produce negative results, due to inadequate natural identity. Therefore, scratchtests with the natural antigens are necessary. Apart from the acute and chronic urticaria, classic other reaction types (Coombs and Gell) within the scope of real food allergy are also present (allergic vasculitis from meat containing penicillin, thrombocyopenic purpura after taking aspirin or quinine); cellular immune reactions to food and its components are also not uncommon. The importance of natural salicylate for the aetiopathogenesis of chronic urticaria has not yet been ascertained; nevertheless, a suitable diet is recommended on the understanding that degranulation of the mast cells, possibly due to subclinical stimuli, is triggered off. PMID- 3327262 TI - [Clinical aspects of renal ischemia and acute renal failure]. AB - The rapid breakdown of renal excretory function termed "acute renal failure" (ARF) is accompanied by an increase in nitrogenous substances in the blood, usually eliminated with the urine (azotemia). Important causes of renal injury are renal ischaemia and the application of nephrotoxic drugs. The period of increasing symptoms (initiation) may be reversed by early therapeutic interventions, while the advanced stage with persistent oligo-/anuria (maintenance) requires haemodialysis treatment. The phase of repair (recovery) is initiated by the polyuric stage of ARF. Even in uncomplicated cases, one should expect only partial restoration of renal concentration ability. PMID- 3327263 TI - [Pathophysiology of global ischemia of the heart]. PMID- 3327264 TI - [Clinical aspects of regional ischemia of the heart]. AB - The clinical aspects of regional myocardial ischemia can be discussed under 3 headings: 1. The clinical pathophysiology comprises: progression of the arteriosclerotic process, modulation of the coronary tone (coronary spasm)- including its underlying factors--, thrombosis and hemorrhagic dissection, as well as modulating factors such as catecholamine release. 2. In the diagnosis the transition of reversible and irreversible myocardial damage may be of special importance. This may be achieved by the ECG, by determination of marker proteins in the serum, and by nuclearcardiology techniques. The diagnosis of variant- or Prizmetal-angina is difficult because if insufficient specificity of the tests. Likewise, for the detection of silent myocardial ischemia by Holter-monitoring, sensitivity and specificity are not yet determined. 3. There are 3 main therapeutic goals: affecting of the arteriosclerotic process, improving prognosis, i.g. in secondary prevention after myocardial infarction, as well as limitation of irreversible myocardial ischemia (myocardial infarction). In this survey all these aspects are discussed in more detail. PMID- 3327265 TI - [The pathophysiology of cerebral circulation]. AB - Local and generalized decreases in cerebral circulation most frequently cause severe functional and morphological disturbances in the central nervous system. During a generalized cerebral ischemia, the appearance of signs of disturbances in electrical and metabolic functions follows a characteristic course. These changes have been demonstrated in experimental examples. In severe hypoxia with occlusion of cerebral arteries, the changes in energy metabolism and electrical phenomena are similar to those in ischemia. The typical signs of oligemic hypoxia, anoxic and hypoxic hypoxia, anemic hypoxia, venous hypoxia and histotoxic hypoxia are characterized in this review. In energy deficient brain tissue the ionic fluxes across the membranes of nerve cells, as well as across the smooth muscle cell membranes of the cerebral artery walls, are of particular interest. Cations have been investigated frequently and in this report the interactions between ions which participate in the regulation of vessel wall tension are discussed. Finally, the redistribution of blood flow after occlusion of single brain-supplying arteries is described. PMID- 3327266 TI - [Experimental principles of tolerance of the brain to ischemia]. AB - The resistance of the brain to ischemia depends not only on the duration and severity of flow reduction but also on a number of pre- and post-ischemic metabolic and hemodynamic factors which are able to improve or impair the post ischemic recovery process. Among pre-ischemic protective factors, the suppression of metabolic rate by drugs or hypothermia, the increase of brain tissue energy reserves and the inhibition of membrane permeability of cations are of particular importance. In contrast, increase of metabolic rate and increase of tissue acidosis induced by hyperglycemia or residual blood flow, reduce the ischemic tolerance of the brain. As long as cell membranes do not depolarize during ischemia, restitution of blood flow results in spontaneous recovery. After depolarization of membranes, however, numerous post-ischemic complications evolve, such as the no-reflow phenomenon, post-ischemic hypoperfusion, post ischemic brain edema, disturbances of the coupling between metabolic activity and blood flow, etc. These complications require therapeutic intervention in order to prevent irreversible injury. By optimizing this therapy in a model of 1 hour complete normothermic brain ischemia in cat and monkeys, post-ischemic recovery of energy metabolism, protein synthesis, spontaneous and evoked electrocortical activity and even integrative neurological performance were observed. The resistance of the brain to ischemia, in consequence, is much higher than previously assumed and can be substantially improved by adequate post-ischemic treatment. PMID- 3327267 TI - Blood-brain barrier and ischaemic brain oedema. AB - According to classification of brain oedema into the cytotoxic and vasogenic types, the latter is closely related to the changes in permeability of the BBB. In cerebral ischaemia, although both types of oedema are involved, the important role of vasogenic oedema, associated with BBB changes, is increasingly recognized. This particularly applies to temporary arterial occlusions in which a biphasic character of two independent BBB openings has been described. The first opening, related mainly to haemodynamic factors, allows leakage of serum proteins into brain tissue and induces vasogenic oedema. The intensity of this oedema can be diminished by reducing the reactive hyperaemia, which promptly follows the release of arterial occlusion. According to recent investigations, infusion of aminophylline appears to be promising in this respect. The other circulatory disturbance, which can affect development of post-ischaemic oedema, is related to the post-ischaemic hypoperfusion which follows reactive hyperaemia. The repeated ischaemic insults during the period of hypoperfusion lead to a pronounced cumulative effect intensifying greatly ischaemic brain oedema and tissue injury. PMID- 3327268 TI - [Johannes Muller in the light of modern scientific history]. PMID- 3327269 TI - [Pathophysiology of renal ischemia]. AB - Renal ischaemia results, early in its course, in cell swelling of those tubule segments which are specifically susceptible to damage. These segments are the straight proximal tubules in the outer stripe of the outer medulla and the medullary thick ascending limb of the loop of Henle in the outer and inner stripe of the outer medulla. One causal predisposing factor for both nephron segments is the sharp decline in the partial pressure of oxygen in the outer medulla. Another important cause for the vulnerability of the thick ascending limb is its strict dependence on a continuous supply of metabolic substrates. The cell swelling caused by ischaemia can be explained, for all nephron segments, as an unchanged uptake of Na+ across the luminal membrane in the face of a reduced pump rate of the basolateral (Na+ + K+)-ATPase. The swelling can be prevented if, for example, in the thick ascending limb the Na+ uptake is inhibited by furosemide. In addition to cell damage by cell swelling, other pathomechanisms are operative in ischaemia. One such mechanism is the damage caused by oxygen radicals. The concentration of these radicals is increased during ischaemia, especially during the initiation of reperfusion. Additionally, the concentration of radical scavengers such as glutathion, is reduced during ischaemia. Future work is needed to define more closely the damage produced by oxygen radicals in terms of lipid peroxidation, ATP and enzyme degradation. PMID- 3327270 TI - [Therapy of cerebral ischemia]. AB - The primary cause of ischaemic neuronal damage is the reduction in the regional cerebral blood flow below the threshold critical for preservation of nervous structures. The development of infarction, however, is not determined only by the severity of ischaemia but also by the duration of a blood flow disturbance below a critical level. During the ischaemic period, and also after reperfusion, secondary mechanisms are triggered (cytotoxic and vasogenic oedema, tissue lactacidosis, entry of Ca++, synthesis of prostaglandins and leukotrienes, production of free radicals and liberation of neurotransmitters), which contribute to the ischaemic cell damage. These pathophysiological mechanisms in the development of ischaemic cell damage suggest three approaches for therapeutic intervention: a. Improvement of cell tolerance against ischaemia b. Increased cerebral blood flow c. Inhibition of secondary damage. a. An improvement of the tolerance of brain cells to ischaemia can be experimentally achieved by hypothermia and barbiturate loading; due to severe side effects, these therapeutical regimens are not clinically applicable. b. An increase in cerebral blood flow, which must be induced within a short period of time, can be obtained by various drugs with different modes of action. While vasodilators are not clinically efficient, haemodilution with low molecular dextran has been shown to be a promising therapeutic concept. Other strategies to improve rheological properties of blood (venesection, other haemodiluting infusions, hydroxyethyl starch drugs acting directly on blood rheology, such as extract of ginkgo biloba) can also be applied. Anticoagulation can be performed only in a few special cases with ischaemic infarction. The increase in perfusion pressure is helpful in hypotonic patients to improve blood supply in the ischaemic region. Cerebral perfusion can also be augmented by drugs which activate function and metabolism. c. Secondary damage to cells surviving the primary ischaemic insult can be inhibited by suppression or diminution of perifocal brain oedema; under ischaemic conditions, osmotherapy is superior to corticosteroids for this purpose. Pathological biochemical mechanisms initiated during or shortly after the ischaemic episode and causing additional cell damage can be influenced by pharmacological interaction (Ca++ entry blockers, inhibitors of prostaglandin synthesis, scavengers of free radicals, e.g. flavones, opiate antagonists). However, the routine application of these drugs in clinical practice still necessitates more controlled trials. Excessive lactacidosis can be controlled by regulation of plasma glucose levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327271 TI - [Pathology of renal ischemia and acute renal failure]. AB - The morphological consequences of acute or chronic renal ischemia may consist of an anemic kidney infarction, bilateral cortical necrosis, acute tubular lesions in circulatory renal failure, so-called subinfarction, as well as arteriosclerotic endstage kidney. In renal biopsies obtained from patients with acute renal failure, renal dysfunction can be morphologically explained by acute intra- and extracapillary necrotizing glomerulonephritis in 50% of cases, and by solely acute tubular lesions in 30% of cases. It is suggested that the development of acute tubular lesions during circulatory insufficiency might be favoured by an angiotensin II-dependent vas efferens constriction, leading to a reduction of peritubular blood flow in the presence of preserved glomerular filtration. The balance between demand and supply of oxygen within the tubular epithelial cells might thereby be critically disturbed. PMID- 3327272 TI - [The lymphatic system--terra incognita? Demonstrated by morphological assessment of resorption processes]. AB - The lymphatic system has been demonstrated by means of special microscopic investigations, using morphologically comprehensive resorption procedures. References has been made to the literature which gives an account of the available knowledge about the lymphatic system and the scientific concepts produced in the course of the centuries. After going into the fundamental morphological principles of parenteral resorption and resorption in the bovine uterus, a description is given of the transport of the vital dyes patent blue violet and Japanese ink, which was followed microscopically in the lymphatic system. A further phenomenon emerges with the concept of persorption, where the particles are in the micron range and have also been identified microscopically in the pathways of the lymphatic system. PMID- 3327274 TI - [Chronicity--an immunologic problem. An analysis exemplified by viral and autoimmune hepatitis]. PMID- 3327275 TI - [Clinical aspects of hypophyseal-hypothalamic diseases]. PMID- 3327273 TI - [Staging in Hodgkin's lymphoma. Exploratory laparotomy with splenectomy]. AB - In the present paper, 66 Studies on exploratory laparotomy with splenectomy in Hodgkin's lymphoma from Western Europe and the USA are presented in tables. This statistical compilation on 7183 laparotomies shows that the spleen was involved in 39.9% (2685 out of 6900 cases investigated), the liver in only 7.7% (446 out of 5789) and the abdominal lymph nodes were involved in 30.3% (1389 out of 4578) of the cases. Altogether, laparotomy with splenectomy led to a change in staging in 33% of the patients (1892 out of 5745). In the period from 1970 to 1986, 123 patients with Hodgkin's lymphoma were laparotomized (and also splenectomied apart from one exception) at the Surgical Division, University of Gottingen. The patients comprised 52 cases in the context of primary staging and 71 cases in the context of secondary staging. In 43 cases (35.2%) the spleen was affected, in seven cases (5.7%) the liver was affected, and there was combination with spleen involvement in each case. Infiltration of abdominal lymph nodes was shown in 38.2% (26/68). Exploratory laparotomy led to a change in stage in 46 cases (37.1%) comprising 28 improvements and 18 deteriorations. Before laparotomy, 15 patients were in stage I, 29 in stage II, 44 in stage III and 21 in stage IV. After pathological staging, 14 were in stage I, 40 were in stage II, 47 were in stage II and 19 were in stage IV. Out of the 14 patients who could not be assigned to any stage before the operation, 11 could be definitively staged afterwards. In addition, lymphography was performed in 103 patients, liver and spleen scintigraphy in 51 patients, sonography in 30 patients and computer tomography in 22 patients. In the re-examination of the lymph node situation in the retroperitoneal space, lymphography attained a specificity of 48% and a sensitivity of 71.4% with a positive prediction precision of 35.7% and a negative prediction precision of 88.8%. PMID- 3327276 TI - Identification of peptidergic nervous control of gastrointestinal functions. PMID- 3327277 TI - [Evolution of the insulin molecule]. PMID- 3327278 TI - [Mechanism of action of insulin]. PMID- 3327279 TI - [Current aspects of diabetic diet]. PMID- 3327280 TI - [Immunopathomechanisms of graft rejection]. PMID- 3327281 TI - [Diabetic retinopathies--internal medicine aspects]. PMID- 3327283 TI - [Indications for drug therapy of arterial hypertension]. PMID- 3327282 TI - [Diabetic polyneuropathies]. PMID- 3327284 TI - [Problems of organ procurement]. PMID- 3327285 TI - [Serologic diagnosis of autoimmune liver diseases]. PMID- 3327287 TI - [Indirect ambulatory, automatic 24 h blood pressure determination: possibilities and limits]. PMID- 3327286 TI - Implications of diabetes in pregnancy for developmental biology. PMID- 3327288 TI - [Historical review: initial attempts at continuous blood glucose determination]. PMID- 3327289 TI - [Infection and septic shock. Pathophysiology (microcirculation and the clinical picture)]. PMID- 3327290 TI - [Role of the artificial heart in heart transplantation]. PMID- 3327291 TI - [Neuropeptides in evolution]. PMID- 3327292 TI - [Gastrointestinal peptides and eating]. PMID- 3327293 TI - [Epidemiology of arteriosclerosis in diabetes mellitus]. PMID- 3327294 TI - [Status of kidney transplantation in the treatment of chronic renal failure]. PMID- 3327295 TI - Obesity, atherosclerosis and diabetes mellitus. PMID- 3327297 TI - [Physiologic and pathophysiologic principles of glomerular permeability to plasma proteins]. PMID- 3327296 TI - [Forms of obesity and metabolic disorders]. PMID- 3327298 TI - [Surgical aspects of kidney transplantation]. PMID- 3327299 TI - [Proteinuria in systemic diseases]. PMID- 3327300 TI - [Diabetes in insulin resistance]. PMID- 3327301 TI - Maturity onset diabetes of the young in Asian Indians. PMID- 3327302 TI - Renal diabetes (primary renal glycosuria): a short overview. PMID- 3327303 TI - [Indications and results of liver transplantation]. PMID- 3327304 TI - [Clinical bone marrow transplantation--indications and results]. PMID- 3327305 TI - [Autoimmunity and internal secretion]. PMID- 3327306 TI - Visual display terminals and workers' health. World Health Organization. PMID- 3327308 TI - Interleukin 2-activated killer lymphocytes in man. PMID- 3327307 TI - The metamorphosis of immunologic science. PMID- 3327309 TI - Secreted class I molecules encoded by the major histocompatibility complex. PMID- 3327310 TI - The major histocompatibility complex and autoimmunity. AB - Study of two diseases with autoimmune characteristics (IDDM and SLE) has demonstrated that alleles carried in the MHC can confer disease susceptibility. The MHC alleles most strongly associated with the development of IDDM are encoded within the class II region (HLA-DR or -DQ). Recent studies indicating that the class III gene products TNF alpha and beta may play a critical role in the initiation of the autoimmune attack on the pancreatic beta-cells have suggested the possibility that the class III region may also contribute to genetic susceptibility in IDDM. In SLE, although there is some evidence suggesting that certain alleles of class II genes may confer disease risk, a more striking association has been detected in the class III region. Deficiency of the class III encoded C4A molecule (either homozygously or heterozygously) shows a high correlation with disease risk. This finding is attractive because C4A plays a central role in the metabolism of immune complexes, the aberrant deposition of which leads to the most prominent alterations in SLE. PMID- 3327311 TI - Autoimmune endocrine diseases. PMID- 3327312 TI - Autoantigen-reactive T cells in neuroimmunology. PMID- 3327313 TI - Lymphocyte hybridomas: 1986. PMID- 3327314 TI - Producing novel antibodies by expression of recombinant immunoglobulin genes. PMID- 3327315 TI - Structure, molecular genetics, and function of complement control proteins: an update. PMID- 3327317 TI - Immunologic developments in AIDS--1986. PMID- 3327316 TI - Toward understanding the mechanism of ciclosporin (cyclosporine) immunosuppression. PMID- 3327318 TI - The prothymocyte: toward a mechanism of commitment? PMID- 3327319 TI - Immunotoxicology--1986. PMID- 3327320 TI - Molecular biology of the T cell receptor. PMID- 3327321 TI - Regulation of the T cell receptor genes: the beginnings of the evidence. PMID- 3327322 TI - Immunocompetent dendritic cells. PMID- 3327324 TI - [Congresses of the East German Society of Surgery. A retrospective review of 4 decades, 1947-1987]. PMID- 3327323 TI - [Our urologic heritage. Eugen Joseph (1879-1933)]. AB - We remember the urologist Eugen Joseph (1879-1933), working in Berlin. After a short description of his life from his extensive scientific work particularly the chromocystoscopy, the chemocoagulation of the tumours of the urinary bladder and the medical technological studies are emphasized, by which he considerably influenced the development of urology in Germany. PMID- 3327325 TI - [Genetic and peristatic aspects of research on twins]. AB - The incidence of multiplets according to Hellin is no more valid in the last years. The reasons have been discussed. Different comprehensions about the valence of the different methodic variants of twin research have been explained. PMID- 3327326 TI - [Bacteriologic studies in premature rupture of fetal membranes and correlation with the clinical aspects of chorioamnionitis and the amnion infection syndrome]. AB - One of the major complications following premature rupture of the membranes (PROM) is ascending infection. In this aspect the bacteria of the vaginal flora play a major part. Bacterial spectra of a group with PROM and another control group with punctual rupture of the membranes are comparatively analysed. This analysis is based on swabs taken from vagina and newborns. Data are interpreted in correlation to clinical picture of chorioamnionitis and amnion infection syndrome (AIS). Twelve newborns clinical suspected to have a neonatal infection are retrospectively judged. In the group with pregnant women with PROM potential pathological germs such as group B streptococci and E. coli are found more often, whereas physiological flora, specially Lactobacillus species, are clearly reduced. In newborns with AIS even germs can be detected, which so far have seemed to be more apathogenic, such as Gardnerella vaginalis. Bacteriological findings are discussed in connection with clinical parameters, specially group B streptococci are looked at more precisely. In newborns with AIS microbiological results are demonstrated including course of pregnancy and delivery. For the management of PROM alternatives are shown and advice for prophylaxis is given. PMID- 3327327 TI - [Endovascular neurosurgery--reflections on the problem in the journal "Voprosy neirokhirurgii"]. PMID- 3327328 TI - [The journal "Voprosy neirokhirurgii im. N.N. Burdenko"--50th anniversary]. PMID- 3327330 TI - [Closed craniocerebral trauma]. PMID- 3327329 TI - [Inventions in neurosurgery in the last 10 years]. PMID- 3327331 TI - [Achievements of vascular neurosurgery]. PMID- 3327332 TI - [Oxidative cellular damage in the digestive system]. PMID- 3327333 TI - Resuscitation and evaluation of victims of blunt multisystem trauma. AB - The initial management of hemodynamically unstable polytrauma patients can be challenging. Although there are other possible causes of hypotension, such as tension pneumothorax, CNS injury and hemopericardium, in the vast majority of blunt trauma victims shock is due to blood loss. Whereas the diagnosis of circulatory collapse is clearcut, the rapid identification and control of the bleeding source may not be a straightforward matter. Such patients often have injuries to several body systems and thus have numerous potential sites of hemorrhage. Ideally, the injury pattern should be defined during resuscitation. The use of a trauma team and standardized protocols facilitate patient management. Clearly, airway patency and adequacy of ventilation must have top priority. Cervical spine immobilization should be maintained until a fracture has been ruled out. In concert with respiratory management, other members of the trauma team should secure adequate vascular access, resuscitate the patient and perform a physical examination. Physical findings dictate the order of further diagnostic and therapeutic maneuvers. In unstable patients the potential need for urgent surgical intervention must not be overlooked. PMID- 3327334 TI - The disposal of intravenous glucose studied using glucose and insulin clamp techniques in sepsis and trauma in man. AB - Whole body glucose uptake and oxidation during a hyperglycemic clamp have been shown to be depressed in hypermetabolic septic patients compared to control subjects despite similar plasma insulin concentrations. Forearm glucose uptake was similarly impaired. Metabolic rate was not increased further by the glucose infusion in the patients although a 20% rise was elicited in the controls. This resistance to the effects of insulin was also clearly demonstrated in trauma patients using the euglycemic clamp technique. The maximal rate of glucose disposal after injury was half that found in controls and the pattern of response was consistent with the insulin resistance being a post-receptor defect. PMID- 3327335 TI - Mediators in trauma. AB - Mediator release associated with polytrauma is responsible for the multifactorial process of posttraumatic organ failure. Mediator action is part of a complex network characterised by a number of major events. Tissue trauma activates specific and unspecific proteolysis in different humoral systems, such as the complement, fibrinolysis and coagulation systems as well as the kallikrein cascade. These provoke release of mediators known to stimulate cellular elements like platelets, granulocytes and macrophages. Activated phagocytes are known to release numerous tissue-damaging and toxic mediators. These are responsible for organ failure, which may terminate as a multi-organ failure syndrome. PMID- 3327336 TI - Anesthesia for trauma. AB - Anesthesia of polytraumatized patients represents a considerable risk for them. The proper treatment of a polytraumatized patient comprises the rapid stabilisation of all his vital functions. At the same time, the attempt must be made to achieve a complete picture of all his injuries in order to be able to select a reliable and safe anesthetic procedure. Over and beyond this, a continuation of all intensive care measures, in particular the optimalization of blood volume, the maintenance of gas exchange, the support of the cardiac, and the balancing of the acid-base and electrolytes, is of the greatest importance for an effective treatment of the polytraumatized patient. PMID- 3327337 TI - Anesthetic management of aortic trauma. AB - Most of the increasing number of ruptures of the thoracic aorta are caused by traffic accidents. Only a minority arrive sufficiently in time at the hospital to receive medical attention. The diagnosis is very difficult to make both on clinical and radiologic findings alone. An aortography is necessary when there is the slightest suspicion of aortic lesion. The lesions are mostly found in the isthmic region of the descending aorta. This and other localisations are easily explained when some specific anatomic, mechanical and congenital factors are considered. Surgical repair should be carried out in all cases as fast as possible. During repair attention must be directed toward the prevention of kidney and spinal cord injury and equally to prevent proximal hypertension and overload during clamping of the aorta. PMID- 3327338 TI - Complications of splenectomy. AB - During the last three decades it has become clear that removal of the spleen, for any reason, is not a benign procedure. In both adults and children splenectomy places the patient at significantly higher risk of overwhelming infection, compared to the normal population. The risk of the post-splenectomy septic syndrome is lifelong and is not eliminated by the administration of polyvalent pneumococcal vaccine. Thus far, the reported rate of overwhelming sepsis in asplenic individuals has ranged from 2.5-13.5%. As more long-term follow-up data become available, it is likely that the true incidence will be 5-10%. In addition to this late complication, splenectomy increases the frequency of adverse events, including death, in the immediate postoperative period. Infections, particularly pulmonary and abdominal sepsis, constitute the majority of the complications. The mortality rate from postoperative sepsis is substantial. Atelectasis, pancreatitis/fistula, pulmonary embolism and bleeding at the operative site are also relatively common occurrences following splenic removal. These alarming statistics have spurred surgeons to change their attitudes concerning splenectomy for trauma, both accidental and iatrogenic. Nonoperative management of hemodynamically stable patients with isolated splenic injury and splenorrhaphy in patients requiring laparotomy are now firmly entrenched in the surgical armamentarium. Patients in whom splenectomy is necessary are given polyvalent pneumococcal vaccine and are instructed to seek early medical attention for febrile illnesses. Splenic autotransplantation and lifelong prophylactic antibiotic therapy have been used in some centers, but their clinical value remains to be proven. PMID- 3327339 TI - Nosocomial infections in severely traumatized patients: magnitude of problem, pathogenesis, prevention and therapy. PMID- 3327340 TI - Assessment of impaired consciousness. PMID- 3327341 TI - Biochemical markers in head injury. PMID- 3327342 TI - Death, brain death. PMID- 3327344 TI - Posttraumatic stress disorder. AB - Posttraumatic stress disorder is an affective disorder resulting from external stress that is beyond what is usual and tolerable for most people. Symptomatology includes particularly intrusive thoughts or dreams and a conscious avoidance of feelings, ideas, or situations related to stressful event. Some psychological reactions seen in the intensive care units can meet the diagnostic criteria for posttraumatic stress. PMID- 3327343 TI - Non-surgical management of spinal cord injuries: a review of studies with the glucocorticoid steroid methylprednisolone. PMID- 3327345 TI - Beneficial effects of the 21-aminosteroid U74006F in acute CNS trauma and hypovolemic shock. PMID- 3327346 TI - Less than severe head injury--an overview. PMID- 3327348 TI - [Experimental leprosy]. PMID- 3327347 TI - [Leprosy in Burundi: apropos of 351 new cases diagnosed in 20 months]. PMID- 3327349 TI - Thesis and proposition for short-term and long-term support of leprosy sufferers. The leprosy bacillus must be cultivated. PMID- 3327350 TI - The difficult decision when to discontinue multidrug therapy in leprosy. PMID- 3327351 TI - [Various classifications of leprosy and their application to the treatment of Hansen disease]. PMID- 3327352 TI - [Clinical and immunological monitoring: intradermal reaction with lepromin. Intra domiciliary contact subjects in Martinique (1980-1985)]. PMID- 3327353 TI - Prevention of thromboembolism in total hip replacement. Aspirin versus dihydroergotamine-heparin. AB - In a prospective and controlled study, we compared the prophylactic effect of high-dose acetylsalicylic acid (ASA) and dihydroergotamine-heparin (DHEH) in 82 patients over 50 years of age undergoing total hip replacement. The patients were screened by pulmonary scan and 125I fibrinogen uptake. Phlebography was done if the 125 I fibrinogen test was positive. According to our criteria, thromboembolism developed in 9 of 40 receiving ASA and in 5 of 42 patients receiving DHEH. The effect of ASA was limited to men; in 16 men on this therapy, none had thromboembolism versus 9 of 24 women. Twenty-two patients showed wound hematomas, but none needed surgical intervention. PMID- 3327354 TI - Penicillin G versus cefuroxime for prophylaxis in lower limb amputation. AB - Out of 457 patients amputated below or above the knee, we randomized 288 to receive penicillin G and 229 cefuroxime as prophylaxis against infection. We also stratified the patients into two groups: Group A (313 patients) who did not receive antibiotic treatment within 48 hours prior to the operation and Group B (88 patients) who did. There were 56 dropouts according to protocol regulations. The patients were evaluated for efficacy on the 21st postoperative day. In Group A, 20 of 158 (13 per cent) penicillin G-treated and 27 of 155 (17 per cent) cefuroxime-treated had wound sepsis; 5 (3 per cent) penicillin G-treated and 4 (3 per cent) cefuroxime-treated patients had been reamputated by Day 21 (P greater than 0.05). We concluded that prophylactic penicillin G prevents infection as effectively as cefuroxime after lower limb amputation. PMID- 3327355 TI - Initiation and enhancement of bone formation. A review. AB - Knowledge of some of the fundamental biochemical factors that may influence the initiation and continued growth of bone-forming cell lines is presented. The discussion is limited to those factors shown experimentally to be present locally in bone tissue and synthesized in the environment of bone-forming cells. The current state of knowledge of basic research findings on osteogenic factors is given in detail. Cooperative actions of these locally produced and systemic factors are the primary stimuli that result in increased bone growth and volume. PMID- 3327356 TI - Lars Ingvar Hansson 1937-1987. PMID- 3327357 TI - Slipped capital femoral epiphysis in southern Sweden 1910-1982. AB - This work is based on 532 cases of physiolysis colli femoris (PCF) in southern Sweden from 1910 through 1982. The material was analyzed epidemiologically. Subsets were used for different investigations aimed at surveying the etiology of PCF, and long-term follow-ups were conducted after various methods of treatment. Finally, the short-term results after hook-pinning, a new device, were evaluated. After radiographic examination of anatomic specimens and normal hips, a method to diagnose and grade PCF was developed. The calcar femoral was found to be of constant shape and position and was used as a landmark to which the position of the femoral head was related. The advantage of this method is that it is easy to use and it is able to determine PCF also after growthplate closure. Epidemiologic analysis of the total material revealed large changes during the 20th century. The disease is more common in males than in females, but the male predominance has decreased from about 90 per cent to about 60 per cent during the period of investigation. Mean age at onset of slipping has decreased by about 3 years in males to 12.7 years and by about 1 year in females to 11.8 years. The incidence has followed a periodic pattern with peaks approximately every 20th year. The mean incidence was 6/10,000 in boys and 3/10,000 in girls. Boys living in the country have always been at higher risk than those living in cities. They were also at higher risk of sustaining bilateral slipping. In girls, there is a seasonal variation, with a higher incidence between May and August. The etiologic investigations dealt with hereditary, mechanical, and hormonal aspects. Radiographic examination revealed PCF in about 10 per cent of the first-degree relatives of 50 consecutive patients with PCF. One third of the families had 2 or more members with PCF. This familial accumulation is much higher than shown in earlier investigations based on questionnaires or clinical reports, and higher than expected from the incidence calculations. The growth analysis using the ICP model showed in both sexes an above average body height before puberty. However, at maturity the heights were almost normal, and accordingly the pubertal gain in height was lower than normal. Both the boys and the girls were markedly overweight before puberty and remained so at maturity. The ICP model accords with what is known about hormonal regulation of growth, and the growth abnormalities indicate a disturbed hormonal growth regulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327358 TI - [Use of carbon fibers in surgery of recent and old lesions of the antero-external cruciate ligament of the knee. Experimental studies in sheep and initial results in human practice]. PMID- 3327359 TI - Developmental stenosis of the bony lumbar vertebral canal. PMID- 3327360 TI - Inhibition of human lymphocyte proliferative response by serum from Plasmodium falciparum infected patients. AB - Malaria infection has been shown to induce alterations in immune reactivity. This report describes the effect of serum obtained from Plasmodium falciparum infected patients on in vitro proliferation of human blood mononuclear cells (BMNC) isolated from healthy individuals. Serum obtained before initiation of treatment suppressed the in vitro lymphocyte proliferative response to both Plasmodium derived antigens and an unrelated antigen (PPD-tuberculin). The suppressive effect was lost if the serum was incubated at 56 degrees C for 30 min, and the effect was not HLA-restricted since the inhibition was seen on both autologous and heterologous BMNC. The degree of suppression was not correlated to the duration of the disease, the degree of parasitemia, or the use of chemoprophylaxis. Sera from 7 patients before and from 3 patients 30 days after initiation of treatment were pooled and fractionated. It was found that the strongest suppressive activity was in the serum fraction containing molecules from 30-100 kD. PMID- 3327361 TI - Degradation of IgA1, IgA2, and S-IgA by Candida and Torulopsis species. AB - Nine strains, isolated from leukoplakias or normal mucosa of the oral cavity, and representing the species Candida albicans, C.tropicalis, and Torulopsis glabrata were tested for the capacity to degrade IgA1, IgA2, and S-IgA in liquid cultures. IgA fragments were characterized by SDS-PAGE of culture supernatants in combination with immunoblotting analysis using antibodies specific for heavy chain and light chain determinants. Strains of C.albicans and C.tropicalis were found to express stronger proteolytic activity than a strain of T.glabrata. The three types of IgA were all degraded, alpha-chains being the primary targets. Immunoblotting analysis indicated that divalent fragments corresponding to the deletion of one or both of the Fc alpha constant domains (F(abc)2 alpha or F(ab)2 alpha) were produced. Monovalent half-molecules corresponding to these fragments could also be detected, suggesting that the yeast strains were capable of cleaving inter-alpha-chain disulphide bridges. The possible consequences of yeast induced degradation for the function of IgA antibodies are discussed. PMID- 3327362 TI - Effects of adenosine on autonomic control of heart rate in man. AB - Six healthy subjects (two female) aged 23-40 years participated in a double-blind randomized cross-over study to investigate autonomic mechanisms involved in the chronotropic effect of adenosine in conscious man. Adenosine was infused in increasing doses following saline, propranolol (0.2 mg kg-1 body weight) or propranolol (0.2 mg kg-1 plus atropine (0.04 mg kg-1). Heart rate and blood pressure were measured supine, on standing and during a Valsalva manoeuvre. Plasma catecholamines were measured in the supine and standing positions. Following saline, adenosine (up to 120 micrograms kg-1 min-1) caused a dose related increase in heart rate (mean +/- SD maximum increase 18 +/- 8 bpm; P less than 0.01). The change in heart rate with adenosine after propranolol (12 +/- 9 bpm; P less than 0.05) did not differ significantly from the corresponding change following saline but was abolished by propranolol plus atropine, which, in turn, was associated with a mean maximum decrease in heart rate of 5 +/- 3 bpm (P less than 0.01). The increase in heart rate during the initial 30 s on standing was augmented with adenosine compared with saline (16 +/- 5 bpm; P less than 0.01). A significant increase in plasma noradrenaline on standing was also found with adenosine compared with saline (6.37 +/- 2.86 vs. 4.77 +/- 1.79 nmol 1(-1); P less than 0.05). The heart rate response to the Valsalva manoeuvre was not affected by adenosine. These results suggest that the positive chronotropic effect of infused adenosine in conscious man may in part be caused by an inhibition of cardiac vagal tone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327363 TI - Interaction of noradrenaline, NPY and VIP with the neurogenic cholinergic response of the rat uterine cervix in vitro. AB - Quantitative pharmacological studies were performed on isolated uterine cervix which was obtained from oophorectomized and oestrogen-treated rats and therefore showed no spontaneous contractility. The concentration-response curves to ACh and carbacholine were to a varying degree depressed and right-shifted in the presence of NA, but not NPY or VIP. The electrically induced cholinergic contraction was potentiated in tissues from animals pretreated with reserpine or 6-OHDA, but only at high stimulation frequencies. Histochemically, both sympatholytics abolished NA from the cervical fibres, whereas immunoreactive NPY was still encountered. Tyramine in the organ bath reduced the contraction amplitude during electrical nerve stimulation concentration-dependently by a beta-adrenoceptor-sensitive mechanism. In the presence of neostigmine the amplitude was reduced by NA, but not by NPY or VIP, which, on the other hand, had an inhibitory effect in the absence of neostigmine. The results offer further support for the view that, although the cervical smooth muscle cells are equipped with adrenoceptors, the neurogenic motor response at low stimulation frequencies (around 3 HZ) is mainly cholinergic. It appears that neurally released NA is able to influence these muscle cells primarily at high frequencies. There is no clear-cut evidence that the inhibitory effects of neural NPY or VIP on the cervix of spayed, oestrogen treated rats are mediated by postjunctional receptors. PMID- 3327364 TI - Effect of insulin-like growth factor-I on metabolism in bovine mesenteric arteries. AB - The effect of insulin-like growth factor-I (IGF-I) on glucose accumulation, amino acid uptake and incorporation of amino acid into protein was studied in arterial smooth muscle. Accumulation of [14C]glucose, uptake of [14C]alpha-aminoisobutyric acid (AIB) and incorporation of [14C]phenylalanine into protein were measured in intima-media preparations of bovine mesenteric arteries (BMA) incubated with IGF I for 2, 4 or 6 h. IGF-I (2.2 nmol l-1) increased the accumulation of glucose into BMA after 4 h (P = 0.0079) and 6 h incubation (P = 0.0027) and in a concentration of 22 nmol l-1) also after 2 h (P = 0.015). The uptake of AIB and the incorporation of phenylalanine were increased after 4 h incubation with 2.2 nmol l-1) IGF-I (P = 0.0045 and P = 0.026, respectively). The effects of IGF-I on all of the metabolic parameters were dependent on incubation time and concentration of IGF-I. Concentration-effect curves were determined for the effect of IGF-I and also for insulin on glucose accumulation in BMA incubated for 6 h. The concentration-effect relationships for IGF-I and insulin were very similar with pD2 values of 7.6 +/- 0.2 (EC50 = 27 nmol l-1) and 7.5 +/- 0.2 (EC50 = 34 nmol l-1), respectively. No additive effect of IGF-I and insulin in supra physiological concentrations (1.0 mumol l-1) could be demonstrated. These results show that IGF-I has metabolic effects which are similar to the effects of insulin in vascular smooth muscle and suggest that IGF-I may be of importance for the metabolism in vascular smooth muscle. PMID- 3327365 TI - Transient expression of insulin-like growth factor I immunoreactivity in skeletal muscle cells during postnatal development in the rat. AB - The immunohistochemical expression of insulin-like growth factor I (IGF-I; somatomedin C) was investigated in hindlimb skeletal muscle of rats during postnatal development. IGF-I immunoreactivity could be demonstrated in satellite fibres and myotubes 1, 2 and 3 days after birth, while no IGF-I immunoreactivity could be demonstrated in the more mature primary fibres. Five days after birth only scattered cells showed IGF-I immunoreactivity and 10 days after birth no specific IGF-I immunoreactivity could be demonstrated in muscle cells, i.e. the adult pattern was established. It is concluded that IGF-I immunoreactivity is expressed during a limited period of postnatal skeletal muscle maturation in rats. IGF-I is probably synthesized by IGF-I immunoreactive muscle cells and contributes to the differentiation/maturation process by autocrine and/or paracrine mechanisms. PMID- 3327366 TI - [Theory of mass madness. Epilogue of the Research Program on Psychiatric Epidemiology of the National Council of Scientific and Technical Research]. AB - This "Metaphysics of Madness" appears as a "sinister mirror of madness", and the madman as a victim of the violence of his conflicts. This has come to reinforce the "tragic" anthropology which was already latent in the ancient pests, in the battles, in the mass suicides. An effort was made to determine the space where madness operates in our cultural context by means of an internationally guaranteed survey of symptoms. The analysis of madness lays out hermeneutics of multiple levels through which the most profound and conflictive structures of our culture become visible. Even if madness is principally entered upon as a psychiatric category, it presents a similar incidence as a category of cultural anthropology, it being necessary to add besides its importance as a literary category, the deciphering of the psychotic discourse as a linguistic category, the necessity of a sociological contextualization and its foundation on philosophic and even theological categories. Madness as a category of the spirit is the daring effort of understanding its liberation "in this deceit of destiny which fools it as to a liberty it has not conquered". After a consideration of texts of two decisive figures related to the philosophic history of madness--Kant and Hegel--the important position of Ludwig Binswanger and his conception of the Ideenflucht (flight of ideas) in the history of psychiatry is brought out. Finally, the theory of the madness of the masses (Massenwahntheorie) stated by Broch--a double madness, of fragmentation, on the one hand, and of aberration and paranoia of power, on the other--shows a universally valid analysis in which the particular, recurrent tragic model of our culture inscribes itself. This model is to be identified with Massenwahntheorie VII, i.e., as a prolongation of the prodigious work carried out by Broch. PMID- 3327368 TI - [Prevention of drug addiction]. PMID- 3327369 TI - Schizoaffective disorder: a dimensional approach. AB - The current categorical approach has not proved successful in resolving the problem of classifying patients with both affective and schizophrenic features. A dimensional approach is suggested; postulating two interacting factors; "dissociotaxia", a neurointegrative abnormality; and "hyperactivation", an abnormality in activation regulation. The latter factor can convert dissociotaxia to associative dyscontrol and produce mixed schizoaffective features. Clinical phenomenological, prognostic, genetic-familial, treatment response and biological evidence is reconsidered from this standpoint; and the preferability of the dimensional approach is suggested, both for understanding the underlying psychopathology, and for constructing a different classification system, extensible to other areas of psychiatry. PMID- 3327367 TI - [2 psychoses and a symbiotic link]. AB - On the basis of the pathology described by Lasegue & Falret, this papers intends to further a psychoanalytic distinction between both types of psychosis which exemplify 'folie a deux'. Hypothesis are proposed which refer to the difference in the psychic structure, in view of the 'body into pieces' experience in Type I delirium cases and a mainly neurotic organization in Type II delirium cases. A case in brought up where part of the interview reveals the rigid as well as sealed bond organization between significant and meaning. Reference is also made to the qualities of symbiotic attachment between both partners in the delirious intercourse, and to the importance the consideration of this diagnostic difference has with regards to the therapeutic strategy. PMID- 3327370 TI - Clonazepam/haloperidol combination therapy in schizophrenia: a double blind study. AB - Clonazepam (CLN), a benzodiazepine originally used as an anti-epileptic, was tested in schizophrenia in a double blind comparison in combination with haloperidol (HL). Twenty-four schizophrenic inpatients, diagnosed according to DSM III were treated with HL and CLN (Group 1) or HL and placebo (Group 2) for 4 weeks. The Brief Psychiatric Rating Scale (BPRS) and the Extrapyramidal Side Effect Scale (EPSE) were used for assessing psychopathological features and extrapyramidal side-effects before treatment and then weekly. No differences in specific schizophrenic symptoms were detected between the two groups, but in Group 1 an early significant BPRS amelioration was noticed compared to Group 2. Moreover, the excitement item improved significantly in Group 1 only, from the second week. Less severe EPSE scores were observed in Group 1 in comparison to Group 2. In conclusion the combination of CLN and HL seems to be preferred to HL alone in cases of psychotic excitement and in order to reduce the severity of extrapyramidal side-effects. PMID- 3327371 TI - Clonidine. AB - Clonidine has provided a nonaddicting solution to an ancient problem, opiate withdrawal without opiates. Gold and colleagues' initial demonstration that this alpha 2 adrenergic agonist could be used to detoxify opiate addicts provided the first nonaddicting treatment for opiate dependency. This discovery has also led to research investigating the utility of clonidine for a number of other neuropsychiatric conditions as well. Clonidine has been studied for use in neonatal narcotic addiction, alcohol detoxification, akathisia, mania, narcolepsy, attention deficit disorder, panic disorder, and alcohol amnestic disorder. Additionally, the clinical application of clonidine was based upon a large body of preclinical research and has opened up other avenues of investigation for non-addictive treatment of opiate dependency. PMID- 3327372 TI - Clonidine and alcohol withdrawal. AB - Clonidine attenuates opiate withdrawal syndrome, via reduction in catecholamine activity in the brain, most probably at the locus ceruleus. Clonidine and locus ceruleus lesions, in animals with alcohol dependency as with the opiates, modify alcohol withdrawal. Both alcohol loading and withdrawal from steady alcohol use alter catecholamines in man and animals. Clonidine's potential to treat alcoholics in withdrawal is reviewed. Several double blind studies showed clonidine, or similar analogues, to be somewhat superior to placebo in acute alcohol withdrawal. Major improvements were in pulse, blood pressure and composite alcohol withdrawal scores. Side effects were minor and mainly included mild sedation, or postural hypotension. In the only available published study clonidine compared reasonably well to a standard sedative in alcohol withdrawal, and greatly influential in plasma catecholamine levels. Other components of alcohol withdrawal, as seizures and hallucinations-delirium tremens have not been documented to change with clonidine. The alpha-2-adrenergic agonists in alcohol treatment seemed modestly effective for treatment of some parts of alcohol withdrawal. They represent a promising, novel, but still investigational approach. Additional data, particularly comparing them to the benzodiazepines, are needed before their potential in therapeutics can be assessed. PMID- 3327374 TI - [Dental pathology (2): Cysts and tumors]. PMID- 3327373 TI - [Studies on ultrasonic diagnosis and ophthalmology (Report 22). Power spectrum analysis of ultrasonic radio-frequency signals in vitreous diseases]. PMID- 3327375 TI - [Ethibloc--a nonsurgical alternative in the treatment of cervicofacial lymphangiomas in children]. PMID- 3327376 TI - Mental health services for deaf students in California. PMID- 3327378 TI - Radon gas: contractor liability for an indoor health hazard. AB - Many families throughout the United States have recently detected dangerously high concentrations of radon gas inside their homes. Radon, a carcinogenic gas produced from uranium, has been discovered in structures overlying uranium bearing rock. This discovery may result in litigation to determine contractor liability for building upon radon-releasing rock sites. This Note examines the strengths and weaknesses of the various theories of contractor liability and considers potential statutory claims under the Clean Air Act. The Note suggests, as an alternative approach to recovery, a proposed regulatory scheme and implementation plan. PMID- 3327377 TI - Deregulating mandatory medical prescription. AB - This Article links the legal evolution of mandatory medical prescription since 1900 to the police-power's prohibition of alcohol and the opiates as well as to the self-interested monopolization of new drugs by physicians. The Article advances a theory of professionalization consistent with the evidence that mandatory prescription is not in the public interest. The Article suggests that the supremacy of self-medication is consistent with competition policy, the medical profession's fiduciary duty to clients, reduced medical costs and improved health. The author analyzes the consequences of regulating drug production, testing, marketing and consumtion by granting decision-making authority to the lowest-cost risk avoider, suggesting this as a plausible basis for legal reform. PMID- 3327379 TI - The kidney: cause or consequence in essential hypertension. AB - Several lines of evidence have implicated the kidney as having a pivotal role in the pathogenesis of essential hypertension. Whatever the initiating factors in an individual patient, it is becoming clear that a renal response must be involved to sustain the elevated blood pressure. There are a number of suggested mechanisms by which the kidney may influence arterial blood pressure. The importance of fluid volume and the role of sodium renal perfusion in elevated blood pressure has been well established. Recent investigations have suggested that sodium and calcium transport defects may exist in patients with essential hypertension. The accumulation of sodium can lead to calcium accumulation; calcium may therefore play an important role in the development of hypertension. Since the key role played by calcium ions in many biologic processes has been recognized, the role of calcium on peripheral vessels as well as the microvasculature of the kidney has become an area of stimulating and exciting research efforts. PMID- 3327380 TI - Calcium-channel-blocking drugs and renal sodium excretion. AB - The administration of calcium-blocking drugs exerts a natriuretic response. Acute studies in isolated perfused kidneys and in experimental animals, as well as in man, consistently demonstrate diuresis, natriuresis, calciuresis, and generally kaliuresis, even in the face of arterial blood pressure reduction. Clearance methodology suggests that calcium-blocking drugs exert their natriuretic response by exerting hemodynamic effects, as well as by acting directly on the proximal tubule. Micropuncture studies and experiments utilizing the toad urinary bladder suggest that calcium-blocking drugs impair sodium reabsorption in the distal tubule. Chronic studies in both animals and man, in which sequential urine collections were made in the face of a known sodium intake, corroborate the natriuretic effects of calcium-blocking drugs. Moreover, these studies suggest that the effects of these medications are likely to be clinically important. PMID- 3327381 TI - Do calcium channel blockers protect against renal ischemia? AB - Data from several studies have indicated that calcium channel blockers may prevent acute renal damage caused by ischemia. If this is true, then the obvious clinical application of this premise would be in surgical cases requiring cross clamping of the aorta, or in patients experiencing prolonged hypotension. Evidence for the mechanism by which calcium channel blockers mitigate injury include the prevention or amelioration of renal vasoconstriction and/or their ability to inhibit calcium entry into cells, thereby possibly preventing toxic calcium 'overload'. Studies of animal models examining ischemic acute renal failure produced either by infusion of vasoconstrictors or by interrupting renal artery blood flow have provided conflicting results. Certain calcium channel blockers afford some degree of protection only when administered prior to the ischemic episode, while others may protect even if given after the insult. Several investigations have been carried out to determine the mechanism(s) of this protective effect. The results indicate cellular calcium accumulation occurs in cells during the anoxic period; this is most pronounced during reflow. This accumulation of calcium appears to be temporally related to both mitochondrial dysfunction and cell death. The ability of the calcium channel blockers to prevent calcium entry into cells may explain their role in protecting the cell and ameliorating ischemic injury. PMID- 3327382 TI - Calcium channel blockers in systemic hypertension. AB - Calcium channel blockers selectively inhibit transmembrane flux of calcium in excitable tissue. Their ability to block calcium-mediated electromechanical coupling in contractile tissue produces peripheral vasodilation and has led to their clinical use in patients with systemic hypertension. The drugs appear to be well tolerated and have excellent safety profiles. Sustained-release preparations allow the drugs to be used once or twice daily. The calcium channel blockers will play an important role in the management of patients with mild, moderate, and severe hypertension when used as monotherapy or when combined with other antihypertensive medications. They can also be used in patients with concomitant diseases, such as angina pectoris and arrhythmia. PMID- 3327383 TI - A radiographic study of porotic hyperostosis. AB - Skull lesions known as porotic hyperostosis have been of interest to researchers since the mid-19th century. The etiology of porotic hyperostosis has long been a matter for speculation yet there has never been complete acceptance or substantiation of any one of the many theories proposed. Today the most widely accepted theory suggests that anemias of either acquired or genetic origin are responsible for porotic hyperostosis. The present study tests this hypothesis using criteria which were chosen after the examination of clinical radiographs of patients with various types of anemia. These criteria are: the presence of "hair on-end" trabeculation, outer table thinning, texture changes, diploic thickening, orbital roof thickening, orbital rim changes, and the underdevelopment of frontal sinuses. A comparison of these criteria from the clinical X-rays with X-rays of skulls with porotic hyperostosis provides a more rigorous, repeatable, and standardized method upon which to base a diagnosis. This approach enables radiography to provide the necessary link between the clinical and anthropological with which to investigate the origin of porotic hyperostosis. PMID- 3327385 TI - American Association of Physical Anthropologists. Membership List. PMID- 3327384 TI - Porotic hyperostosis: new evidence to support the anemia theory. AB - The etiology of skull lesions known as porotic hyperostosis has long been a matter for speculation. The most widely accepted theory at present suggests that an anemia, either acquired or genetic, is responsible for lesion development. However, acceptance of this theory is not universal and the nature of the relationship between orbital and vault lesions remains a controversial issue. This paper provides a much broader field of supportive evidence on which to base the anemia theory. This involves a synthesis of information from the clinical and anthropological literature as well as new data from two skeletal collections: Poundbury Camp, a Romano-British series, and the Hodgson collection, a 19th century East Asian series. A comparison is made between clinical and anthropological data at the macroscopic, microscopic, radiographic, and demographic levels of analysis. This approach reveals the similarities in expression between clinically diagnosed anemias and porotic hyperostosis. PMID- 3327386 TI - [Ultrasonic screening of pregnant women]. PMID- 3327387 TI - [Clinical research on Kalipsol (ketamine hydrochloride) used in subanesthetic doses in minor operations in obstetrics and gynecology]. PMID- 3327388 TI - [Use of echography in the diagnosis of gynatresia in girls]. PMID- 3327390 TI - [Clinical trial of the use of escin in the postoperative treatment of episiotomies]. PMID- 3327389 TI - [Estrogen production in physiological and pathological states]. PMID- 3327391 TI - [Hemodynamic changes caused by laparotomy during aorto-iliac surgery]. AB - A haemodynamic study was carried out on 53 patients undergoing elective surgery of the abdominal aorta in order to assess the haemodynamic changes consequent to abdominal manipulations prior to aortic clamping. Surgery was carried out under general anaesthesia and ventilation was controlled. The following parameters were monitored: mean arterial pressure (Pa), cardiac index (CI), systolic index (SI), systemic vascular resistances (Rsa), pulmonary vascular resistances (Rpa), heart rate (fC). Cutaneous circulation was monitored using a photoplethysmographic transducer. The following haemodynamic pattern was seen as the peritoneal cavity was opened and traction on the mesentery was applied: CI +40.7%; fC +28.61%; SI +9.85%; Rsa -39.16%; Rpa -28.43%; Pa -15.7%. The recording of the facial cutaneous photoplethysmographic wave showed an increase of 50%. In some extreme cases, a state of cardiovascular collapse with marked cutaneous erythema strongly resembling anaphylactic shock ensued. The physiopathology of these cardiovascular reactions is unclear, but the haemodynamic pattern as well as the cutaneous vasodilation suggest a stimulation of both vagal and sympathetic nervous systems and the release of vasoactive substances into the general circulation. PMID- 3327392 TI - [Effects of anesthetic agents on hepatic blood flow]. PMID- 3327393 TI - [Anesthesia and peroperative resuscitation in liver transplantation]. PMID- 3327394 TI - [Early diagnosis in pediatrics]. PMID- 3327395 TI - [Early diagnosis of pathology of the urinary tract. Round table]. PMID- 3327396 TI - [Symptoms and signs of alarm in pediatrics]. PMID- 3327397 TI - [Prospective and retrospective analysis of Spanish pediatrics in the last few years]. PMID- 3327398 TI - [Pediatric education in the last 40 years]. PMID- 3327400 TI - [Outpatient care]. PMID- 3327399 TI - [Methods of screening and early diagnosis]. PMID- 3327401 TI - [Hospital care]. PMID- 3327403 TI - [Psychological problems of the sick child]. PMID- 3327402 TI - [Nutrition and chronic disease]. PMID- 3327404 TI - [Malformations of the central nervous system. Round table]. PMID- 3327405 TI - [The meaning of Pierre Janet's work]. PMID- 3327406 TI - [Electroconvulsive therapy: new technical aspects]. PMID- 3327407 TI - Magnetic microspheres for the targeted controlled release of drugs and diagnostic agents. PMID- 3327408 TI - Biopharmaceutics of microparticulate drug carriers. PMID- 3327409 TI - Drug delivery to macrophages for the therapy of cancer and infectious diseases. AB - The mechanisms by which mononuclear phagocytes discriminate between self and nonself, recognize foreign materials, senescent, damaged, old, or effete cells, and tumor cells are unknown. However, regardless of the mechanism(s) involved, once activated by the appropriate signal(s), macrophages are able to selectively recognize and destroy neoplastic cells in vitro and in vivo. Liposomes injected intravenously, in common with other particulate or polymeric matrices, localize preferentially in organs with high mononuclear phagocyte activity and in circulating blood monocytes. This behavior allows microparticulates to serve as a convenient system for the selective delivery of encapsulated drugs to cells of the mononuclear phagocyte series in vivo. Liposomes are a particularly attractive experimental system because of their capacity to incorporate a wide variety of water-soluble and lipid-soluble drugs. At this time, however, there is no reason to assume that a liposome-based drug delivery system will offer any significant therapeutic advantage compared to other microparticulate drug delivery systems. As in commercial development of any pharmaceutical preparation, considerations of cost-of-goods, shelf life, and acceptance of the formulation and dosing regimen by both physicians and patients will be of major importance in determining success and widespread clinical use. Liposomes containing macrophage-activating agents are highly effective at augmenting macrophage-mediated tumoricidal activity in vitro eradicating tumor metastasis in vivo, as well as protecting animals from a wide variety of microbial and viral infections. Although the demands of solving the scientific and technical problems associated with liposome development are substantial, the rapid rate of progress in biology and in pharmaceutical sciences enhances the prospect of success for at least several aspects of liposome-mediated drug delivery. The next few years will be crucial in determining whether the commercial development of liposomes is feasible or whether they will join the ranks of other drug carrier designs that have failed to fulfill their initial promise. PMID- 3327410 TI - Development of an immunotoxin with in vivo efficacy for murine systems. PMID- 3327411 TI - Intracellular pathways of ricin A chain cytotoxins. AB - Ricin A chain, a potent ribosomal poison, was disulfide linked either to the iron transport protein, transferrin, or to anti-transferrin receptor antibodies to produce highly specific derivative toxins, Tf-A and TfR-A, respectively. The ability of these agents to gain access to and damage ribosomes within the cell was accelerated in the presence of carboxylic ionophores. Their effectiveness for killing clonogenic target cells was correspondingly enhanced by 5 logs after a brief treatment with Tf-A plus ionophore. Intracellular trafficking of Tf-A and TfR-A was monitored by a variety of methods to better understand their mechanism of action. Data obtained with 125I-labeled A chain and 59Fe3+-labeled toxin probes indicated that the natural iron delivery pathway was initially followed. This was characterized by specific attachment to surface receptors, internalization, entry into low-density acidic vesicles, uncoupling of iron, an absence of lysosomal degradation, and sustained cycling. Ultrastructural studies using a colloidal gold-labeled anti-A chain probe confirmed the presence of these toxins within the structural elements associated with endocytosis. Toxic Tf-A molecules, however, diverged from this pathway (t1/2 = 88 min) to eventually kill cells as witnessed by a gradual loss in the ability to rescue cells using excess transferrin. Potentiating agents, such as carboxylic ionophores or B chain, seem to act by speeding the divergence of Tf-A and TfR-A from the normal endocytotoxic cycle. PMID- 3327412 TI - Genetically engineered antibody molecules and their application. AB - Immunoglobulin genes can be efficiently expressed following transfection into myeloma cells. Using protoplast fusion, transfection frequencies greater than 10( 3) can be achieved. Compatible plasmids containing two different selectible markers are used to simultaneously deliver heavy and light chain genes to the same cell. To produce molecules with differing specificities the rearranged and expressed variable regions can be cloned from the appropriate hybridoma. In some cases, variable regions from cDNAs can be inserted into the expression vectors. It is possible to manipulate the immunoglobulin genes and produce novel antibody molecules. Antibodies have been produced in which the variable regions from mouse antibodies have been joined to human constant regions. In addition, antibodies with altered constant regions have been produced. These genetically engineered antibodies provide a unique set of reagents to study structure-function relationships within the molecule. They also can potentially be used in the diagnosis and therapy of human disease. PMID- 3327414 TI - Targeting enzyme albumin conjugates. Examining the magic bullet. PMID- 3327413 TI - The pharmacology of monoclonal antibodies. PMID- 3327416 TI - Retrovirus-mediated gene transfer into hematopoietic stem cells. AB - The ability to transfer new genetic information into murine and human hematopoietic cells with retrovirus vectors offers a powerful approach to identifying the molecular mechanisms governing stem cell development. The newly integrated provirus also serves as a clonal marker for elucidating the lineage relationships of the cells in the stem cell hierarchy. High efficiency gene transfer into human cells opens the way to developing new therapy for treating genetic diseases by introducing functional genes into deficient cells. Present transplantation technology would only permit gene therapy with bone marrow cells. However, as gene transfer and transplantation technologies improve it may be possible to consider treating diseases that affect other organs and tissues. I would like to acknowledge the support of Alan Bernstein and R. Phillips in whose labs the murine work was carried out during a post-doctoral fellowship. I also thank Sharon Kerbel for excellent assistance in the preparation of this manuscript. PMID- 3327415 TI - An approach to chemotherapy based on base sequence information and nucleic acid chemistry. Matagen (masking tape for gene expression). PMID- 3327417 TI - Some perspectives on targeted delivery with prodrugs. AB - Targeted delivery using prodrugs is becoming an important means for studying approaches to the efficient delivery for complex and often toxic molecules to specific sites within the body. Especially true for polymeric prodrugs containing targeting moieties, the future offers many possibilities for improvement of the therapeutic ratio by delivering drugs exclusively to diseased cellular and subcellular components within the organism. The fact that this type of research is highly interdisciplinary in nature requires the creative input of the biology disciplines as well as chemistry and pharmaceutical science. Our perspective on what constitutes the true delivery system, as it applies to targeted delivery, needs to be redefined. The use of the prodrug to target drug molecules to specific sites is merely the chemical delivery device that has been conceived and designed after considering the implications of those biochemical, physiological, and immunological processes that ultimately affect the transport and distribution of the prodrug within the host organism. PMID- 3327418 TI - Transdermal iontophoretic delivery of therapeutic peptides/proteins. I: Insulin. PMID- 3327419 TI - Targeting of liposomes to tumor cells in vivo. PMID- 3327420 TI - Lipid emulsions as drug delivery systems. PMID- 3327421 TI - The hypothalamic-pituitary-adrenal axis revisited. A symposium in honor of Dorothy Krieger and Edward Herbert. New York, April 6-8, 1987. PMID- 3327422 TI - The CRH motoneuron: differential peptide regulation in neurons with possible synaptic, paracrine, and endocrine outputs. PMID- 3327423 TI - The synthesis and processing of pro-ACTH/endorphin in the developing rat pituitary. AB - In many aspects of pro-ACTH/endorphin processing, newborn melanocytes are mature by birth. The newborn melanocytes correctly process precursor to many of the expected products including alpha MSH and beta-endorphin, the melanocytes perform tissue-specific modifications such as alpha-N-acetylation and additional proteolytic steps and they respond to dopaminergic agents but not to physiological levels of CRF or glucocorticoids. These features are retained in serum-free cultures of newborn intermediate pituitary cells. Thus, the major developmental alterations in the intermediate pituitary melanotropes involve the net 150-fold rise in pro-ACTH/endorphin synthetic rate, from birth to adulthood. In contrast, processing of pro-ACTH/endorphin in the newborn anterior lobe is not mature by birth. Both in vivo and in vitro newborn anterior pituitary corticotropes contain a large pool of pro-ACTH/endorphin, and a substantial amount of ACTH(1-39) is cleaved to ACTH(1-13)NH2 and CLIP. Surprisingly, the amount of ACTH(1-13)NH2 and beta-endorphin rises with increasing time in culture, but alpha-N-acetylation of ACTH(1-13)NH2 or beta-endorphin is not seen in the corticotropes. As in the adult, the synthesis of pro-ACTH/endorphin in newborn corticotropes is subject to regulation by CRF and glucocorticoids. In addition, glucocorticoid treatment of newborn corticotropes acts to suppress the cleavage of ACTH(1-39) to ACTH(1-13)NH2 and of beta-LPH to beta-endorphin, rendering the treated corticotropes more like the adult corticotropes. This plasticity in processing observed in the newborn corticotropes is not seen in the adult. It will be important to examine whether peptide processing patterns which are changed during this period of plasticity are permanently altered, and then what the consequences of those altered processing patterns might be. PMID- 3327424 TI - Corticosteroid receptor types in brain: regulation and putative function. PMID- 3327425 TI - Corticosteroid receptors in brain: relationship of receptors to effects in stress and aging. PMID- 3327426 TI - Mechanisms of chemical-induced porphyrinopathies. PMID- 3327427 TI - Genetic regulation of the heme pathway. PMID- 3327428 TI - Porphyrinurias and occupational disease. AB - Pathologic porphyrinuria in man is based on a complex etiology and pathogenesis. In hepatic porphyrias, coproporphyrinuria is usually only one of the pathognomostic porphyrin parameters in the urine. Secondary coproporphyrinuria means that an increased excretion of coproporphyrin occurs as the biochemically dominant symptom of a disturbance in porphyrin and heme metabolism during an intoxication, individual condition, or basic disease. Certain foreign and environmental chemicals, such as hexachlorobenzene, polyhalogenated aromatic hydrocarbons, vinyl chloride, and dioxin, alter the heme pathway functionally. Increased porphyrinuria can follow as a toxic response that is differentiated into secondary coproporphyrinuria and chronic hepatic porphyria. This is characterized by a simultaneous increase in hepatic and urinary uroporphyrin and heptacarboxylic porphyrins, owing to inhibition of hepatic uroporphyrinogen decarboxylase. Most of the coproporphyrinurias observed in man are caused by alcohol ingestion. Dioxin, vinyl chloride, and polyhalogenated biphenyls induce an incipient subclinical stage of chronic hepatic porphyria in persons with normal red cell uroporphyrinogen decarboxylase. In contrast, exposure to dioxin on the part of persons with inherited uroporphyrinogen decarboxylase deficiency can cause latent chronic hepatic porphyria to develop into PCT. Coproporphyrinuria and latent chronic hepatic porphyria do not produce clinical symptoms. Secondary porphyrinuria with transition to chronic hepatic porphyria is a metabolic response following various toxic and pathologic conditions; it serves as a sensitive index for chemical exposure and occupational disease. PMID- 3327429 TI - Hormonal regulation of the heme pathway. PMID- 3327430 TI - The dermatologic manifestations of human porphyria. PMID- 3327431 TI - Alterations in renal heme biosynthesis during metal nephrotoxicity. AB - The regulation of the heme biosynthetic pathway in the kidney by various metals has been reviewed. In addition, a study on the effects of lead on renal heme biosynthesis after acute treatment of rats has been reported. Chronic low-level lead exposure in rats results in relatively small effects on renal heme biosynthetic pathway enzymes. After acute treatment of rats with lead, no effects on ALAD or UROS and mild, transitory effects on ALAS and ferrochelatase are observed. The intracellular binding of lead within intranuclear inclusion bodies in the proximal tubule cells and to high-affinity cytosolic lead-binding proteins probably protects sensitive subcellular systems, such as the heme pathway, from lead toxicity. Chronic exposure to methyl mercury results in increased urinary excretion of uro- and coproporphyrins in rats, mediated via inhibition of ferrochelatase and UROS and stimulation of ALAS. A tissue-specific inhibition of ALAD occurs in the kidney after treatment of rats with indium. Acute treatment of rats with nickel, platinum, tin, antimony, bismuth, and cobalt results in induction of heme oxygenase, followed by decreased microsomal heme content and ALAS stimulation in the kidney. PMID- 3327433 TI - Occurrence and biological properties of N-methyl protoporphyrin. PMID- 3327434 TI - Mechanisms of toxicity of photoactivated artificial porphyrins. Role of porphyrin protein interactions. PMID- 3327432 TI - Lead-induced abnormalities of porphyrin metabolism. The relationship with iron deficiency. PMID- 3327435 TI - Principles for application of porphyrin markers in epidemiological studies. PMID- 3327436 TI - Metal-induced alterations of delta-aminolevulinic acid dehydratase. AB - ALAD is a cytoplasmic enzyme that catalyzes the second step of the heme biosynthesis pathway, that is, the condensation of two molecules of delta aminolevulinic acid into porphobilinogen. ALAD is a zinc-dependent enzyme; thiol groups are essential for its activity; and in vitro experiments show that ALAD can be activated or inhibited by several metal ions including A;3+, Pb2+, Cd2+, Hg2+, Ag2+, and Cu2+. To explain these effects, it has been postulated that metals bind to thiol groups of allosteric sites and, according to their structure, provoke allosteric transitions to the active or inactive form of the enzyme. Under current environmental and occupational exposure levels, lead is practically the only metal that can affect ALAD activity. Erythrocyte ALAD is the most sensitive indicator of lead exposure: effects of exposure are detectable even when blood lead levels are within the "normal" range. Zinc protects ALAD in vitro and in vivo from the inhibitory effect of lead. There is also some suggestion that aluminum could be responsible for the decreased erythrocyte ALAD activity observed in patients on chronic hemodialysis. PMID- 3327437 TI - Metal alteration of uroporphyrinogen decarboxylase and coproporphyrinogen oxidase. AB - Both UD and CO are susceptible to alteration by sulfhydryl-directed binding agents including a variety of trace metals. UD apparently requires a functional SH group or groups for catalytic activity, and the various steps of decarboxylation catalyzed by the enzyme can be differentially inhibited by divalent cations such as Hg2+ at very low concentrations. There is evidence that tissue-specific factors such as the endogenous GSH concentration may influence the susceptibility of UD in some tissues to metal inhibition, and this circumstance could be highly relevant to the etiology of porphyrinopathies or porphyrinurias that arise during prolonged metal exposures. CO does not appear to have a requirement for functional SH groups at the active site, but several SH groups on the enzyme appear to be involved in maintaining the protein's noncovalent structural characteristics. CO appears to be substantially more readily inhibited by metals in vivo than in vitro. This observation may reflect effects of metals on both the structural integrity of the enzyme is functionally associated in the intact cell. Finally, it seems reasonable to suggest that tissues, such as the kidney, that ordinarily contribute only sparingly to total excreted porphyrin levels may assume increased importance in this regard when challenged by specific porphyrinogenic chemicals such as trace metals. Advantage might be taken of such chemical- and organ-specific changes in porphyrin metabolism and porphyrin excretion patterns in monitoring prolonged, subclinical exposure to such chemicals in human populations. PMID- 3327438 TI - Metal induction of heme oxygenase. AB - The experimental data that have been reviewed support the following conclusions regarding metal induction of microsomal heme oxygenase activity: 1. Induction of heme oxygenase in liver, kidney, and other organs of rodents is a nonspecific, toxic response to parenteral administration of numerous metal compounds. 2. The Co2+ and Cd2+ ions are especially potent for induction of heme oxygenase in rat liver; Sn2+, Ni2+, and As3+ are especially potent for induction of the enzyme in rat kidney; Hg2+ is especially potent for induction of the enzyme in rat adrenal. 3. Rat spleen, testis, and brain are relatively refractory to metal induction of heme oxygenase activity; in testicular microsomes from Cd2+-treated rats, heme oxygenase activity is markedly inhibited. 4. Metal induction of heme oxygenase requires de novo synthesis of mRNA and protein, based on 1) experiments with metabolic inhibitors (actinomycin D, puromycin, and cycloheximide) and 2) translation assays of heme oxygenase mRNA. 5. Heme oxygenase induction by metals is generally suppressed by treatments with SH compounds (for example, cysteine and glutathione) and enhanced by agents that deplete tissue SH levels (for example, diethyl maleate), suggesting that the induction mechanism may involve binding of metal ions to SH-containing regulatory molecules. 6. Administration of DDC exerts a pronounced synergistic effect on Ni2+ induction of heme oxygenase activity in rat tissues, attributable in part to enhanced cellular uptake of nickel. 7. Induction of heme oxygenase is not sustained during repeated daily treatments of rats with NiCl2, pointing to an adaptive mechanism for tolerance to the enzyme inducer. Investigations of metal induction of heme oxygenase activity have commonly involved sc or ip administration of the test compounds to rats. The paucity of studies in other species and the dearth of experiments with oral or respiratory exposures hinder extrapolations of the animal data to human environmental or occupational exposures to metal compounds. PMID- 3327439 TI - Zinc protoporphyrin. Past, present, and future. AB - The course of zinc protoporphyrin research has progressed at an increasingly rapid pace on several fronts. A variety of biochemical and clinical evidence viewed in toto now suggests that ferrochelatase catalyzes zinc protoporphyrin formation in states of relative iron-deficient erythropoiesis and in lead inhibited iron metabolism. Furthermore, a redefinition of the relationship of zinc protoporphyrin to certain other parameters of iron status has been made based upon changes during the earliest states of iron depletion. These clinical studies show that the zinc protoporphyrin level and the ferritin level vary in concert but that changes in the percent transferrin saturation and in the hematocrit results are less consistent. Thus zinc protoporphyrin and ferritin are closely linked metabolically such that iron-deficient erythropoiesis becomes an initial manifestation of iron depletion. The measurement and expression of results as mumoles zinc protoporphyrin/mole heme have improved the quality of results, partly by the elimination of the assumed hematocrit designed into existing instruments. Other refinements in hematofluorometry technology have permitted exploration of the potentially extensive applications of zinc protoporphyrin measurements for lead surveillance and diagnosis, blood banking, pediatrics, obstetrics, sports medicine, and other clinical situations where a very sensitive, cost-effective indication of iron status is required. PMID- 3327440 TI - Role of cytochrome P-450 in porphyria caused by halogenated aromatic compounds. PMID- 3327441 TI - [Recurrence of cervical carcinoma (bibliographic review)]. PMID- 3327442 TI - [Screening for Chlamydia trachomatis and Streptococcus beta hemolyticus group B in the course of amnioscopy]. PMID- 3327443 TI - Dietary recommendations in cancer prevention. AB - In order to prevent diet-induced cancer, many countries regulate the use of food additives (e.g. nitrites) and control the level of harmful substances, such as pesticide residues and mycotoxins in food. In most affluent countries therefore, these factors play a minor role in cancer causation. The dietary intake of agents preventing cancer, such as nutrients, dietary fibre and some natural components in plants is probably of much greater importance in cancer prevention. So far there are only general recommendations promoting increased consumption of food rich in these substances. Some international and national organizations have published dietary guidelines specifically intended to decrease the risk of cancer. In many respects, the recommendations given in these guidelines do not differ from those published during the last decades with the aim of preventing, for example, cardiovascular diseases. They all stress the need to decrease the intake of fat and sodium and to increase the consumption of foods rich in dietary fibre and nutrients such as vitamins A, C and E. PMID- 3327444 TI - Sonography as an adjunct to plain film in the evaluation of acute abdominal pain. AB - A prospective clinical study was made in order to determine the value of routine sonography in conjunction with plain abdominal films on 150 patients with acute abdominal symptoms. In 23% important diagnostic information was achieved, most commonly in acute biliary disease. Less important pathological entities were revealed in 21% of the patients. In 1% sonography yielded misleading information. The use of sonography should be increased and it might be recommended as an adjunct to plain film evaluation in patients with acute abdomen if plain films do not reveal the reason for abdominal symptoms. PMID- 3327446 TI - The development of human linkage analysis. AB - The principles of linkage detection and measurement are traced from the first discovery of linkage to its present-day use in human genetics. Some indications are given of their success and of the present problems and challenges facing them. PMID- 3327445 TI - Intravenous indomethacin as postoperative analgesic in children: acute effects on blood pressure, heart rate, body temperature and bleeding. AB - To study the effect of intravenous indomethacin on blood pressure, heart rate, body temperature and post-operative bleeding we performed a double-blind, placebo controlled study on 100 operated children, aged 1-16 years. At the end of operation intravenous indomethacin 0.35 mg/kg followed by an infusion of 0.07 mg/kg/h for 24 h combined with standard doses of morphine according to clinical needs resulted in better postoperative analgesia than morphine alone. During the two first hours the systolic and diastolic blood pressure and ventilation rate did not differ between the groups. The heart rate was significantly lower (p less than 0.001) in the indomethacin group. Indomethacin did not prolong the bleeding time. Mild to moderate bleeding was observed in 13 indomethacin--and five placebo treated patients (p less than 0.05). The bleeding did not, however, require any intervention. The mean body temperature did not differ between the two groups in the evening following the operation, but was significantly lower (p less than 0.01) on the first postoperative morning in the indomethacin group. Six patients (12%) in the placebo group had fever over 38 degrees C and paracetamol was administered to four of them. Clinically diminished diuresis was not observed. Since prophylactic indomethacin infusion improves the postoperative analgesia in children and no clinically important unwanted effects were seen, it may be used in children, over one year of age in whom non-steroidal anti-inflammatory drugs are not contraindicated. PMID- 3327447 TI - A general survey of genetics and cancer. AB - As the molecular details of cancer have begun to unfold, it has become apparent that the cellular genetic apparatus is defective in the malignant cell. Accordingly, we have attempted to review the prominent aspects of genetics research as it impinges on the problem of cancer. Although the field is immense, we have tried to cover four major areas: human genetics, molecular genetics, somatic cell genetics, and developmental genetics. Oncogenes are considered in detail in all of these areas, and a new map (42 entries) of oncogene positions on human chromosomes is presented. PMID- 3327448 TI - Induction of differentiation of human phaeochromocytoma cells in culture by epidermal growth factor and insulin. AB - A primary culture of malignant phaeochromocytoma cells obtained from a left adrenal tumor of a 56 year old woman complaining of occasional palpitation and headache was established. The addition of epidermal growth factor (EGF) and insulin to the culture medium induced a profound development of network formation of axon-like processes. At the same time, the secretion of catecholamines from cultured cells was also increased. EGF and insulin were demonstrated to induce the differentiation of malignant phaeochromocytoma cells in primary culture. PMID- 3327449 TI - Immunofluorescent studies of the anti-microtubule effects of the anti-cancer drug estramustine. AB - Immunofluorescent studies in human prostatic carcinoma cells (DU 145) and cultured squirrel fish epithelial cells (a non-cancer cell) revealed that estramustine, a conjugate of estradiol and nor-nitrogen mustard, possessed microtubule disassembly properties. Sixty microM estramustine produced disassembly at both the proximal and distal ends of microtubules, producing short pieces of less than 2 microM which were "wavy" and oriented in a random manner. With increased time of drug exposure these short microtubules disappeared, to be accompanied by a gradual disassembly of a small population of longer microtubules (greater than 7-8 microM). In dividing DU 145 cells it was possible to show a different degree of sensitivity of specific microtubule-containing cellular structures. In mitotic figures the asters were most sensitive and disappeared completely following exposure to estramustine. These were followed by the "pole to-pole" and "chromosomal" fibers. In cytokinesis, the intercellular fibers between daughter cells were comparatively resistant to the drug. Estramustine did not induce disassembly of the vimentin filaments in non-dividing or dividing cells but did cause their collapse around the nucleus or the mitotic apparatus. These data suggest that specific microtubules have differing sensitivity to estramustine. PMID- 3327450 TI - Natural antibodies against the carcinoembryonic antigen (CEA) and a related antigen, NCA, in human sera. AB - Natural antibodies directed against CEA and a related antigen, NCA, have been demonstrated in all normal and pathological sera using an EIA, although they have never been detected by RIA. These antibodies are not anti-blood group antibodies, as their titer was decreased only slightly by absorption with blood group substances. The study of their reactivity with deglycosylated antigens demonstrated that they were directed against peptidic epitopes. Antibodies against NCA or CEA, purified using specific immunosorbents, cross-reacted with all the antigens of the "CEA family" but not or only weakly with unrelated antigens. PMID- 3327452 TI - Cytotoxic and antitumor effect of a fraction from cell-free extract of group A Streptococcus on transplantable tumor cells. AB - A fraction (60F) which had cytotoxic and antitumor activity could be obtained by precipitating cell-free extract (CFE) of group A streptococcus (Su strain) with a 50% to 60% saturation of ammonium sulfate. 60F exhibited a potent inhibitory effect on the incorporation of 3H-thymidine into various types of transplantable tumor cells. The activity of 60F was reduced by proteases and heating at 45 degrees C, but not by glycosidases and nucleases. Furthermore, 60F showed antitumor activity, such as cure and prolongation of life, in animals bearing EAC, MM-2, and S-180 tumors. These results show that 60F is probably protein and essentially exerts cytotoxic action against every cell line of tumor tested in vitro, and that the antitumor activity of 60F in vivo depends on the transplantability of tumor cells. PMID- 3327451 TI - Testing a predictive regression model for response in adult acute myeloid leukemia comparing two induction regimens of the E.O.R.T.C. -AML-5 and AML-6 trial. AB - Pretreatment characteristics of 295 adults with acute myeloid leukemia who were treated in a large cooperative group of the E.O.R.T.C. between 1976 and 1982 (AML 5) have been evaluated to assess their value as prognostic indicators. Logistic regression methods were applied to derive a model for prediction of achievement of CR. The model was tested prospectively in an independent group of 274 subsequent patients treated with a different but similar induction regimen (AML 6), who were matched in all eligibility criteria. The concordance between the observed percentage of response in the AML-6 trial population and the expected response given by the model built on the AML-5 study was very close for the good response subgroups (WBC less than 50,000/mm3 and age less than 60 yrs), while the discrepancies in the poor prognostic groups were considerable. Furthermore, our study shows that the prognostic value of factors may shift as treatment strategies change and that caution is necessary in applying conclusions from a preceding trial to a current patient population. PMID- 3327453 TI - Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. AB - Mitoxantrone is similar to Adriblastin in its mechanism of action and antitumor activity. Objective remissions were obtained in 20-30% pretreated patients and in 23-44% of untreated patients by single-drug treatment of patients suffering from metastatic breast cancer. The objective response rates to Mitoxantrone in combination with CTX, 5-FU, MTX, VCR, MMC. Prednimustine or Vindesine were 16-46% in treatment and 38-89% in primary treatment. Randomized studies comparing Mitoxantrone with Adriblastin in single-drug and combination treatment did not show any significant differences in efficacy. However, Mitoxantrone was significantly less toxic. Remission rates of between 24 and 54% were achieved by single-drug treatment in pretreated patients suffering from non-Hodgkin lymphoma. Mitoxantrone appears to be active in ovarian cancer, lung cancer and hepatocellular carcinoma. PMID- 3327454 TI - Interleukin 3 like activity secreted from human ras or myc transfected rodent cells. AB - We have examined the secretion of IL-3 like activity from recipient normal mouse, rat and Chinese or Syrian hamster cells and their derivative cell lines obtained after transfection with recombinant plasmids carrying an exogenous human ras or myc gene. IL-3 like activity was determined by two cell proliferation assays which employed the FDC-P1 and 32D IL-3 dependent mouse cell lines. The colorimetric MTT assay, where a tetrazolium salt is employed, and the trypan blue dye exclusion assay were used. Low serum containing supernatants from rat or Syrian hamster lines expressing an exogenous human normal or mutant T24 H-ras1 gene supported the proliferation of the IL-3 dependent FDC-P1 or 32D cells. However, supernatants from mouse BalbC or Chinese hamster cells expressing the normal or mutant T24 H-ras1 gene failed to support the proliferation of these cells. In addition, supernatants from rat 208F or BalbC cells transfected with recombinant plasmids carrying a human myc gene supported the proliferation of the two IL-3 dependent cell lines. Our results suggest that introduction of the human Ha-ras1 or human myc gene can trigger the secretion of IL-3 like growth factors in some but not all rodent cells. PMID- 3327455 TI - Elevated expression of the myc gene in human benign and malignant breast lesions compared to normal tissue. AB - Expression of the c-myc gene in human breast lesions and in adjacent normal tissue was studied by immunohistochemical analysis. The previously described monoclonal antibody Myc1-9E10 (1) which recognizes the p62 c-myc protein was used in paraffin tissue sections. A total of 101 cases of breast disease examined included 38 simple and complex cystic disease, 18 simple and hyperplastic fibroadenomas, 36 ductal and lobular carcinomas and 9 in situ carcinomas. Whereas the adjacent normal tissue was slightly positive, 25 out of 38 cystic disease, 7 out of 18 fibroadenoma, 36 out of 36 carcinoma and 9 out of 9 in situ carcinoma specimens showed moderate to high levels of p62 c-myc expression as indicated by staining intensity. These results suggest that the c-myc protein may play a role in breast neoplasia. PMID- 3327457 TI - Volume dedicated to the memory of Laurence M. Sandler (1929-1987). PMID- 3327456 TI - Epidemiologic aspects of malignant melanoma (review). AB - The incidence of malignant melanoma has increased worldwide, the rate in Germany being about 12 per 100,000. Geographic variations are due to genetic or racial factors rather than to excess sun exposure. A white complexion with freckles or multiple dysplastic nevi are important danger signs. Large and even small congenital nevi are potential precursors to melanoma. The prevention of melanoma is based on the recognition of risk factors, the identification and removal of precursor lesions and an improved detection of initial melanomas by physicians and lay persons. The so-called millimeter rule has proved to be useful in this connection. PMID- 3327458 TI - Population genetics history: a personal view. PMID- 3327459 TI - DNA methylation in Escherichia coli. PMID- 3327460 TI - Sex determination and dosage compensation in Caenorhabditis elegans. PMID- 3327462 TI - Mechanism and control of homologous recombination in Escherichia coli. PMID- 3327461 TI - The genetics of active transport in bacteria. PMID- 3327464 TI - Genetics of biological rhythms in Drosophila. PMID- 3327465 TI - Genetic recombination in bacteria: a discovery account. PMID- 3327463 TI - Analysis of alcohol dehydrogenase gene expression in Drosophila. PMID- 3327466 TI - Genetic analysis of the yeast cytoskeleton. PMID- 3327467 TI - The bithorax complex. PMID- 3327468 TI - Oncogene activation by chromosome translocation in human malignancy. PMID- 3327469 TI - The essential role of recombination in phage T4 growth. PMID- 3327470 TI - Regulation of DNA replication during Drosophila development. PMID- 3327471 TI - The genetic system, the deme, and the origin of species. PMID- 3327472 TI - Regulatory proteins in yeast. PMID- 3327473 TI - Natural variation in the genetic code. PMID- 3327474 TI - Arabidopsis thaliana. PMID- 3327475 TI - Neural induction. AB - The molecular mechanism of neural induction of embryonic cells is an important but poorly understood problem in neuroembryology. Glycoconjugates in the target cell plasma membrane and/or its structural organization play a key role in the reception of the inductive signal. It is the competent target tissue itself which probably contains the capacity and specificity for neuralization. However, the mechanism of transmission of the signal which leads to activation of the intracellular machinery involved in the process of neural determination remains to be elucidated. With respect to the information acquired by the target cells during neural induction, and the early events in differentiation, neuronal precursor cells have been shown to have acquired the potential to display a high degree of biochemical and phenotypic differentiation, even in the absence of further embryonic influences. PMID- 3327476 TI - [20 years' existence of the Parasitology Service of the Medical Faculty of Kinshasa, Zaire]. PMID- 3327477 TI - [Risk of infection with chemoresistant Plasmodium falciparum according to Anopheles density and infectivity. Application to West and Central Africa]. PMID- 3327478 TI - Clinical manifestations of Wuchereria bancrofti filariasis in an endemic village in the Nile Delta. PMID- 3327479 TI - [Histologic aspects of pleural mesothelioma]. AB - The authors present four cases of malignant mesothelioma of pleura. Mean of age of our patients is 34 years. Two of them are men, the two others are women. The histologic study shows that our cases are represented by one of epithelial type, one of sarcomatoid type and the two last of mixed biphasic type. The authors insist, in the basis of literature data, in the importance of the positive and differential diagnosis concerning the primitive and secondary epithelial tumors of the lung. The means of diagnosis are represented currently by cytology and histopathology and also by cytochemistry and immunohistochemistry. PMID- 3327480 TI - [Endosalpingosis: apropos of a case of colonic localization]. AB - The endosalpingosis is a benign affection which is in the most often asymptomatic. It means the presence of tubal mucosa in ectopic location; often in the tubal wall; the pelvic peritoneal and adjacent lymph node. We present here a colic endosalpingosis case with intestinal occlusion. We review in this purpose the literature, and discuss the etiopathogenicity. It shows that a previously tubal affection can have a great part in the birth of this pathology. PMID- 3327482 TI - Correlations between titres from direct immunofluorescence and bioassay for assessment of potency of "Celvivac" swine fever live vaccine. PMID- 3327481 TI - [Fibro-inflammatory polyposis of the stomach: apropos of a case]. AB - The stomach fibro-inflammatory-polyp is distinguished from the eosinophilic granuloma by some authors because of their geographic assessments. It is an inflammatory affection represented by a pseudo tumoral lesion. We present a case concerning a woman, 62 years old, who presented since 10 years a Biermer anaemia; a neoplastic affection was suspected, and then denied by histopathologic exam. We shall discuss the pathogenic and therapeutic data proposed by the literature. Recently, the treatment of this benign lesion consists in endoscopic resection. There no recurrence or malignant degeneration. PMID- 3327483 TI - [Idiopathic aortic thrombosis in a full-term newborn infant]. AB - A case of idiopathic aortic thrombosis in a term neonate is reported. Ultrasound examination led to diagnosis and an embolectomy was carried out. Literature data concerning etiology and treatment of neonatal aortic thrombosis are reviewed. PMID- 3327484 TI - [Cholestatic form of viral hepatitis and thickening of the walls of the intrahepatic bile ducts]. AB - A biphasic acute hepatitis A is reported in a child. The cholestatic form of the second episode was associated with an ultrasonographic thickening of the gallbladder and intrahepatic bile duct walls. A possible relationship between the abnormal US appearance of intrahepatic bile ducts and cholestasis is discussed. PMID- 3327485 TI - [Various indications for antibiotherapy in perinatal Streptococcus B infections]. PMID- 3327486 TI - [Studies on the mechanism developing bronchial asthma due to Candida albicans. 4. Relationship of three different antibodies against Candida albicans (Candida), IgE antibody, precipitin and hemagglutinin to severity of Candida-induced asthma and to type of response after bronchial provocation test]. PMID- 3327487 TI - Allergic bronchopulmonary aspergillosis. PMID- 3327488 TI - [The effects of lead on reproduction: review of data from human studies and animal experiments]. PMID- 3327489 TI - [Gastric epithelioid leiomyoma (leiomyoblastoma). Analysis of a case and review of the literature]. AB - The authors report a case of gastric epithelial leiomyoma (leiomyoblastoma). Macroscopically, such tumors resemble leiomyoma, with a biological behavior between leiomyoma and leiomyosarcoma. A review of the medical literature indicates that gastrointestinal bleeding is the most usual manifestation. Gastrointestinal seriography and endoscopy are the most utilized diagnostic exams. The endoscopic biopsy, many times, is unable to confirm the malignant or benign nature of the tumor. It is emphasized the importance of identifying the potentially malignant tendency of the tumor, indicated, mainly, by histology and mitotic counting. The treatment is surgical and consists of local or gastric resection, according to the neoplastic localization, its extension, infiltration, biological nature and the presence of multiple tumors. In the case reported, the patient was operated in urgency because of hemoperitoneum and the source of bleeding was a neoplastic vessel in the anterior wall of the antrum, which was not resected at that time. Later on, a biopsy of the gastric tumor performed during a routine surgery disclosed the real nature of the disease. Once the histopathological diagnostic was made and its potential malignant evolution detected the patient was re-operated. A partial gastrectomy with removal of the antrum was performed. Now, the patient has been asymptomatic with no evidences of metastasis after 30 months of the diagnostic. PMID- 3327490 TI - [Breast feeding vs. acute diarrhea]. AB - The defense factors found in human breast milk and the correlation between shortened duration of breast feeding in low income populations, with gastroenteritis and diarrhea, are revised. The changes in intestinal flora and the morbidity and mortality caused by early weaning are detailed. PMID- 3327491 TI - Effects of exogenous growth hormone on milk production and nutrient uptake by muscle and mammary tissues of dairy cows in mid-lactation. AB - Responses to exogenous growth hormone were measured in lactating dairy cows surgically prepared to allow measurement of nutrient exchanges across mammary and hind-limb muscle tissues. Cows were injected daily with either saline or growth hormone, at a dose of 0.1 mg/kg liveweight, over periods of 6 days. During administration of growth hormone milk yield, milk fat content and yields of milk fat protein and lactose increased. Arterial plasma concentrations of glucose and non-esterified fatty acids were increased, uptake of glucose by leg muscle tissue decreased, lactate release from leg muscle tended to increase, mammary uptake of non-esterified fatty acids increased, blood flow to leg muscle tended to increase and blood flow to mammary tissue increased during injection of growth hormone. The results show that growth hormone affects supply to and utilization of key nutrients by tissues, resulting in the supply to the mammary gland of additional precursors for milk synthesis. PMID- 3327493 TI - Immunologic effects of low levels of ochratoxin A in ovo: utilization of a chicken embryo model. AB - Ochratoxin A (OA) was administered to 13-day-old chicken embryos via the chorioallantoic membrane. The 7-day LD50 value (day 20 incubation) of OA was calculated at 7.9 micrograms of OA. Ochratoxin-treated embryos (2.5 micrograms) had slight but significant changes in numbers of immunoglobulin-bearing cells in the bursa but not in the spleen. Chicks hatched from in ovo-treated eggs were challenged with 9 X 10(4) colony-forming units (CFU) of beta-hemolytic Escherichia coli (O1:K1) at 7 days of age via the thoracic air sac. Lesion scores of OA-treated chicks were equal to or less severe than those of controls. Hatchmates of the above chicks were vaccinated with a homologous killed E. coli bacterin (O1:K1) at both 2 and 4 weeks of age and challenged with 10(4) CFU of E. coli at 7 weeks. Post-challenge lesions were present in three vaccinated untreated controls and no OA-treated chicks. We conclude that although in ovo exposure to OA may marginally suppress immunoglobulin-bearing cells of bursa, chicks hatched from OA-treated eggs respond as well as controls to an antigen and resist infection by a virulent organism. PMID- 3327492 TI - Control of steroidogenesis in small and large bovine luteal cells. AB - Evidence was cited to show that: (1) prostacyclin (PGI2) plays a luteotrophic role in the bovine corpus luteum and that products of the lipoxygenase pathway of arachidonic acid metabolism, especially 5-hydroxyeicosatetraenoic acid play luteolytic roles; (2) oxytocin of luteal cell origin plays a role in development, and possibly in regression, of the bovine corpus luteum; and (3) luteal cells arise from two sources; the characteristic small luteal cells at all stages of the oestrous cycle and pregnancy are of theca cell origin; the large cells are of granulosa cell origin early in the cycle, but a population of theca-derived large cells appears later in the cycle. Results of in vitro studies with total dispersed cells and essentially pure preparations of large and small luteal cells indicate that: (1) the recently described Ca2+-polyphosphoinositol-protein kinase C second messenger system is involved in progesterone synthesis in the bovine corpus luteum; (2) activation of protein kinase C is stimulatory to progesterone synthesis in the small luteal cells; (3) activation of protein kinase C has no effect on progesterone synthesis in the large luteal cells; and (4) protein kinase C exerts its luteotrophic effect in total cell preparations, in part at least, by stimulating the production of prostacyclin. The protein kinase C system may cause down regulation of LH receptors in the large cells. PMID- 3327494 TI - Stress-induced activation of the sympathetic nervous system. AB - Discrepancies between perceptions of internal or external circumstances and innate or acquired expectations lead to patterned stress responses involving several homeostatic systems, of which the sympathoadrenomedullary system (SAMS) is one. Severe, generalized threats such as hypoglycaemia, hypoxia, haemorrhage, circulatory collapse, and fight/flight situations elicit generalized SAMS activation, including cardiac stimulation, splanchnic, cutaneous, and renal vasoconstriction, and usually preserved skeletal muscle blood flow. Patterned sympathetic neural responses, resulting in redistribution of blood volume or changes in glandular activity, occur during orthostasis, exercise, altered environmental temperature, the postprandial state, and performance of attention requiring tasks. In all these situations, SAMS activity is co-ordinated with that of the parasympathetic nervous system, the pituitary-adrenocortical system, and probably several neuropeptide systems. Although acute stress-induced SAMS activation can be a health hazard, the role of chronically repeated, stress induced SAMS activation in the development of cardiovascular disease remains unclear. Benzodiazepines, beta-adrenoceptor blockers, and alpha 2-adrenoceptor agonists can attenuate effects of stress-induced SAMS activation, but pressor responses often are maintained. PMID- 3327495 TI - Physical stress and catecholamine release. AB - In both health and disease, noradrenaline and adrenaline concentrations in plasma increase with intensity and duration of exercise (Figure 1). These changes are only to a minor extent due to decreased catecholamine clearance (Figure 2). The increase in sympathoadrenal activity during exercise is primarily elicited by feed-forward stimulation from motor centres in the brain (Figure 3, Table 1), and by afferent impulses from working muscles (Figure 4). During continued exercise, changes in internal milieu may enhance the catecholamine response. Of particular interest from a metabolic point of view is the fact that during exercise a decrease in plasma glucose causes a relatively large increase in plasma adrenaline (Figure 5). Sympathoadrenal activity is of major importance for exercise capacity. By depressing insulin secretion, as well as by direct effects on target tissues, sympathoadrenal activity enhances mobilization of glycogen as well as triglyceride from both extra- and intramuscular depots. After training, noradrenaline responses to given absolute work loads are reduced, while responses to given relative loads, i.e. work load in percent of individual work capacity, VO2/VO2max%, are unchanged. Prolonged endurance training may increase the size and secretory capacity of the adrenal medulla (Figure 7, Table 2), an adaptation which may improve exercise capacity. Differences in catecholamine levels cannot explain the fact that physically-active individuals have a lower cardiac mortality than inactive ones. PMID- 3327496 TI - The neuroendocrinology of physical injury. AB - Physical injury of any sort--accidental injury, burns or elective surgery- provokes an immediate neuroendocrine response. Neural input arising from the cerebral cortex, damaged tissues and receptors detecting fluid loss leads to increased secretion of ACTH, growth hormone, prolactin and vasopressin from the pituitary, and to a general activation of the sympathetic nervous system, with rises in adrenaline and noradrenaline concentrations. Secondary changes include stimulation of cortisol and aldosterone and inhibition of insulin and somatomedin secretion. The glucagon concentration and plasma renin activity may also be increased, either immediately or after a delay. The duration of these responses generally depends upon the severity of the injury and differs considerably between hormones, for reasons that are not understood. The only endocrine changes consistently seen at later times after trauma are an increase in insulin secretion, which supersedes the initial suppression, and decreases in the concentrations of T3 and gonadal steroids. Some of the changes in steroid, thyroid and pancreatic hormones differ temporally or even qualitatively from those of their usual stimuli and are unexplained. The initial neuroendocrine response to injury can be construed as playing a defensive role, but the function of the later changes is not understood; it seems likely that they are adaptive in nature, but the scope for therapeutic intervention remains unclear. PMID- 3327497 TI - The effects of stress on salt and water balance. AB - The effect of 'stress' on salt and water balance is largely determined by intrinsic renal factors supported by a series of inter-related neuro-humoral mechanisms which serve to enhance salt and water reabsorption and to maintain arterial pressure. As shown by acute hypovolaemic stress, the hormone response is characterized by increased renin-angiotensin production and associated hyperaldosteronism, which is further augmented by states of Na+ depletion. As well as increasing aldosterone secretion, angiotensin II has a direct renal effect to increase Na+ retention, and may stimulate both thirst and arginine vasopressin secretion. Additional support to volume homeostasis is provided by increased secretion of hypothalamic hormones (arginine vasopressin and corticotrophin releasing factor) and activation of the sympathetic nervous system, which further enhances renin secretion. These mechanisms, in restoring extracellular fluid volume and renal perfusion pressure, eventually diminish the stimuli to renin once normovolaemia is achieved. A variety of other acute 'stressors', not associated with major changes in ECF volume or hypotension, also stimulate adrenocortical hormones (cortisol and aldosterone), renin and arginine vasopressin. The biological significance of these changes is uncertain, but their brief duration make it unlikely that the responses contribute significantly to changes in salt or water balance. Atrial peptide hormones could also be important in ECF volume regulation. However, recent studies show little if any change in basal plasma atrial natriuretic peptide levels during acute hypovolaemic stress, whereas severe treadmill exercise (but not surgical stress or acute hypoglycaemia) stimulates venous levels in man. The relevance of these findings to the regulation of salt and water balance during stress clearly requires further study. PMID- 3327498 TI - Prolactin, growth hormone and thyrotropin-thyroid hormone secretion during stress states in man. AB - Changes in hormone secretion and/or metabolism almost constantly accompany stressful events. The hormonal response to stress is directly related to the intensity of the stimulus, and greatly depends on the individual's perception of potentially stressful situations. Hypoglycaemia, surgery and exercise represent physical, metabolic and psychological stressful events where the activation of the endocrine system plays a great role. These endocrine responses also include the secretion of GH and prolactin, but the response pattern varies with the stimulus. Hypoglycaemia, exercise and surgery are potent stimuli to GH and prolactin release, both in men and women. The available data suggest that prolactin is more responsive than GH to surgical stress, whereas physical exercise and hypoglycaemia preferentially stimulate GH secretion. Prolactin levels during hypoglycaemia rise solely when symptomatic neuroglycopenia is achieved. By contrast, prolactin and GH responses to purely psychological stress are rarely seen, although some forms of reproductive stress may potentiate prolactin release in women. A teleologically satisfactory rationale for the acute GH and prolactin rise in response to these stressful stimuli is not clearly apparent in man. No definite metabolic activity of prolactin on intermediate metabolism has been demonstrated, although prolactin is mildly diabetogenic. The known metabolic actions of GH do not appear to be critical during surgery or acute hypoglycaemia, although GH probably participates in the regulation of metabolic homeostasis during chronic hypoglycaemia and chronic exercise. Changes in secretion and/or metabolism of hypothalamic neurotransmitters can increase the secretion of GH by increasing the secretion of GHRH or by decreasing the secretion of somatostatin. The prolactin rise is brought about by either a decrease in dopamine activity, an increased secretion of a hypothetical PRF, or by both mechanisms. Since multiple neuronal pathways converge on the hypothalamus from many other parts of the brain, the pronounced effects of hypoglycaemia, exercise and surgery on the secretion of GH and prolactin also reflect the action of different and complex neural inputs on the activity of the hypothalamic pituitary axis. However, the morpho-functional mapping of these excitatory pathways still remains incomplete. TSH secretion is tightly regulated by the negative feed-back mechanism exerted by thyroid hormones. The small changes in TSH level observed during surgery and physical exercise seem to reflect mainly alterations in peripheral T4 metabolism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327499 TI - Opioid peptides in blood and cerebrospinal fluid during acute stress. AB - The opioid peptides beta-endorphin and [met]enkephalin are present in the peripheral circulation. Plasma beta-endorphin originates from the pituitary gland and its cosecretion with ACTH is stimulated by a variety of noxious stimuli. Although the adrenal medulla contains high concentrations of [met]enkephalin containing polypeptides which are costored with catecholamines, and although the adrenal gland appears to secrete [met]enkephalin into the adrenal vein, the relative adrenal contribution to plasma [met]enkephalin appears to be negligible. Plasma concentrations of immunoreactive [met]enkephalin may be increased by insulin and by endotoxic shock, but they are not significantly altered by acute haemorrhagic stress nor by surgical stress. Thus blood plasma concentrations of beta-endorphin, but not of [met]enkephalin, are generally increased during acute stress. The physiological significance of endogenous opioids in the circulation is not known. It is unlikely that transient increases in the concentrations of opioid peptides in peripherally circulating blood modulate nociception, since the peptides do not enter ventricular cerebrospinal fluid in detectable amounts under these conditions. Recent evidence has raised the possibility that circulating opioids may be involved in regulating blood glucose and in activating the immune system. It is also possible that circulating beta-endorphin and related polypeptides have non-opioid actions on a variety of peripheral tissues. PMID- 3327501 TI - Neuroendocrine responses to social stress. PMID- 3327500 TI - Cardiovascular responses to stress: the role of opioid peptides. PMID- 3327503 TI - Neuro-anaesthesia: the present position. AB - Over the years the basic principles underlying the practice of neuroanaesthesia have not changed, but introduction of new anaesthetic agents and associated techniques have improved the ability of the neuroanaesthetist to "fine tune" the patients physiological state. This has improved the capacity of the neuroanaesthetist to mitigate the inevitable fluctuations which occur and prevent their ill effects. Further improvement is still desirable and possible. It takes years for the correct plan of usage of new drugs to be formulated for the clinical situation, and their relationships established to new techniques of patient monitoring. Like neurosurgery itself neuroanaesthesia shows no signs of approaching a final definitive state in the forseeable future. PMID- 3327502 TI - [Study of the structural-functional properties of immunoglobulins G and their fragments using 1H-NMR]. AB - Data on NMR-spectroscopy studies of the structure-function interrelation in immunoglobulins G and their proteolytic fragments are reviewed. Relationship between structural and dynamic characteristics of immunoglobulins G and their functional properties is discussed. PMID- 3327505 TI - Physiological, inflammatory and neuropathic pain. PMID- 3327504 TI - Stable xenon CT/CBF imaging: laboratory and clinical experience. PMID- 3327507 TI - Dorsal root entry zone (DREZ) thermocoagulation. PMID- 3327506 TI - Spinal cord stimulation for spasticity. PMID- 3327508 TI - [Diagnosis and therapy of hemorrhage caused by esophageal varices]. PMID- 3327509 TI - [Glossary of commonly used expressions in the undergraduate courses of human parasitology]. PMID- 3327510 TI - [Immunologic aspects of idiopathic dilated cardiomyopathy]. AB - Pathological and clinical aspects of primary cardiomyopathies are briefly discussed in the first part of the review. The immunological mechanisms involved in the pathogenesis of dilated cardiomyopathy are then summarized with more details, owing to the elevated number of scientific data concerning the disease. The Authors also discuss about the fields to be further clarified in the next future in order to gain better knowledge on the pathogenesis of idiopathic dilated cardiomyopathy. PMID- 3327511 TI - [Multicenter study of antirabies antibodies in vaccinated subjects: comparison of serologic methods]. AB - Polycentric research is performed in three laboratories to value the immunological response in vaccinated persons against rabies. The serological methods were: the immunoenzymatic test with virus of HDCV vaccine (EIA-V) and viral glycoprotein purified (EIA-P), the neutralizing in vitro test (RFFIT) and the immunofluorescent indirect test (IFI). The sera of 119 subjects were examined by three laboratories, every performed a different test. It is observed a concordance of 98.3% between RFFIT and EIA-V, of 86.8% between RFFIT and EIA-P, of 80.5% between RFFIT and IFI. The RFFIT is the method more sensible and specific for rabies antibody, but more expensive and difficult. The IFI showed late nucleocapsid antibodies and more false positive and negative cases. The EIA V and EIA-P are efficient, sensible, specific, and not expensive routine methods to point out protective titres of antibodies, above 0.5 UI/ml after 15 day the inoculation of vaccine HDCV. PMID- 3327512 TI - Indirect immunofluorescence application in the epidemiological study of hepatitis A. AB - We used IIF test for seroepidemiological study on 531 sera divided in age-groups obtained from apparently healthy subjects of Rome. Our results confirm the endemicity of HAV (Hepatitis A virus) infection in Rome with a prevalence of more than 50%. The application of the anti-HAV IIF (Indirect Immunofluorescence) test to a large number of sera demonstrated its usefulness as a quantitative and qualitative test in the epidemiological field. PMID- 3327513 TI - Thymopentine treatment improves clinical and immunological functions in aged subjects with chronic bronchitis. AB - The effect of in vivo thymopentine treatment (50 mg/subcutaneously every other day for six weeks) on clinical features and in vitro immunological parameters was evaluated in ten aged patients with chronic bronchitis. In vitro immunological studies were performed before and after treatment both on phenotypic (OK monoclonal defined lymphocyte subpopulations) and functional parameters (blastogenic responses to polyclonal mitogens Concanavalin-A and Phytoemagglutinine). Thymopentine did not significantly affect lymphocyte subpopulations, which were reduced before pharmacological treatment, when compared to those of young healthy controls. Peripheral blood lymphocytes blastogenic response to polyclonal mitogens was restored, even though proliferation did not reach the values of young healthy subjects. Thymopentine treatment significantly improved lymphocyte functions, without being able, however, to overcome completely the age-dependent loss of blastogenic responses. Nevertheless the favourable evolution of clinical symptoms we observed in our study may be, at least in part, related to the improvement in vivo of those immunological functions that we studied in vitro. Eight out of ten patients showed an evident improvement of symptoms and signs of chronic bronchitis after thymopentine treatment and four of them arrived to a complete remission from infectious episodes. No side effects were noted. Although still preliminary, these results seem to be encouraging as thymopentine could be used with success as an immunomodulating agent in aged people. PMID- 3327514 TI - [Morphology of astrocytes--past, present, and future]. PMID- 3327515 TI - [Light and electron microscopic observations of cysts in the brain from an autopsy case of cryptococcus meningitis]. AB - We gave some considerations to the significance of cyst formation in a case of cryptococcus meningitis by examining the cysts themselves and comparing the organisms in the cysts with those disseminated throughout the subarachnoid space by light and electron microscopy. An 18-year-old girl had complained of headache, stiffneck and fever at the onset. These symptoms worsened into confusion without any definite diagnosis, then resulted in an arrest of spontaneous respiration which led to use of respirator for 12 days. The patient died 40 days after the onset. The brain weighed 1440 g and showed moderate swelling with opacity of the leptomeninges, which was very evident over the convexity and around the basal side of the pons. Subarachnoid fresh hemorrhage was also observed around the basal side of the brain stem. Microscopic examination of the subarachnoid space revealed widely disseminated Cryptococcus neoformans varied in size, whose cell wall showed a positive staining reaction to PAS. The organisms had characteristic spicules positively stained with cresyl violet radiating out of the cell body, and were associated with infiltration of lymphocytes, macrophages and polymorphonuclear leukocytes throughout the subarachnoid space. Some portions of arachnoid membrane, dura mater and vessel walls in the subarachnoid space especially the adventitia of the basilar artery were replaced by multiple cysts. The cysts were tightly filled with large numbers of small uniformly sized organisms which often showed budding. These cysts showed no histological evidence for inflammation. Further studies to demonstrate those differences were carried out with electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327516 TI - [Traumatic posterior fossa hematoma]. AB - The traumatic posterior fossa hematoma was regarded as relatively rare thing, but recently, as the result of the prevalence of CT scanners, the number of reported cases is increasing. We report nine cases of traumatic posterior fossa hematoma. We divided into two categories: one was the acute epidural hematoma, the other was the acute subdural hematoma with cerebellar contusion. Five were cases of the acute epidural hematoma, three were cases of the acute subdural hematoma with cerebellar contusion and a case had both an epidural and a subdural hematoma. All the cases had struck the occipital region and had the occipital bone fracture. The prognosis of the five cases of the acute epidural hematoma was excellent, but that of the four cases of the acute subdural hematoma with cerebellar contusion was poor and they all died inspite of the removal of the hematoma executed in three cases. We estimated that the hitting forth was extremely strong in cases of the subdural hematoma with cerebellar contusion, and that the momentary deformity of the occipital bone might injure the cerebellum directly. Once a hematoma was produced in the posterior fossa, it oppresses the brainstem and causes the acute hydrocephalus, so the state of consciousness and respiration deteriorate suddenly. In cases of the acute epidural hematoma, appropriate surgical intervention could save the patients and resulted in good outcome. But in some cases of the fulminant type acute epidural hematoma of the posterior fossa caused by tearing the sinuses, though we have not experienced, patients die before the diagnosis and treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327517 TI - Age-related increase in a cathepsin D like protease that degrades brain microtubule-associated proteins. AB - In microtubules isolated from brains of very old rats, two of the major microtubule-associated proteins, MAP1 and MAP2, are found only in degraded form. MAP1 is present as a piece whose molecular weight on sodium dodecyl sulfate polyacrylamide gel electrophoresis is circa 50,000 smaller than the native protein, and MAP2 is extensively fragmented. The native forms of both proteins are present in tissue homogenates but are rapidly degraded during microtubule isolation. The proteolytic activity responsible for this degradation is cathepsin D like, being more active at acid pH than neutral and being completely blocked by pepstatin at 10(-7) M. Fractionation of aged brain supernatant by gel permeation chromatography showed that the MAP1 and MAP2 degrading activity elutes with a single peak of cathepsin D like activity. MAP1 and MAP2 are known to promote microtubule assembly, and their degradation by a protease whose levels increase with age could be related to defective microtubule assembly which is known to occur in age-related degenerative conditions such as Alzheimer's disease. PMID- 3327518 TI - Mechanism of action of Escherichia coli endonuclease III. AB - Endonuclease III isolated from Escherichia coli has been shown to have both N glycosylase and apurinic/apyrimidinic (AP) endonuclease activities. A nicking assay was used to show that the enzyme exhibited a preference for form I DNA when DNA containing thymine glycol was used as a substrate. This preference was reduced or eliminated either when the DNA was relaxed or when the type of damage was altered to urea residues or AP sites. The combined N-glycosylase/AP endonuclease activity was at least 10-fold higher than the AP endonuclease activity alone when urea-containing DNA was used as a substrate as compared to AP DNA. When DNA containing thymine glycol was used as a substrate, the combined N glycosylase/AP endonuclease activity was about 2-fold higher than the AP endonuclease activity. Yet, when DNA containing thymine glycol or urea was used as substrate, no apurinic sites remained. Furthermore, magnesium selectively inhibited endonuclease III activity when AP DNA was used as a substrate but had no effect when DNA containing either urea or thymine glycol was used as substrate. These data suggest that both the N-glycosylase and AP endonuclease activities of endonuclease III reside on the same molecule or are in very tight association and that these activities act in concert, with the N-glycosylase reaction preceding the AP endonuclease reaction. PMID- 3327520 TI - Protection of oligonucleotide primers against degradation by DNA polymerase I. AB - By use of a mutational assay employing an octadecamer with a mismatch in the center, it is shown that the introduction of phosphorothioate groups near the 5' end can protect the mismatch against degradation by the 5'-3'-exonuclease activity of Escherichia coli DNA polymerase I. An optimal level of protection is achieved when the phosphorothioate groups are incorporated in at least the second and third internucleotidic linkages from the 5'-end. However, gel electrophoretic analysis as well as the use of an octadecamer with a mismatch closer to the 5' end in the mutational assay reveals that degradation of the oligonucleotide is not completely blocked but only slowed down. PMID- 3327519 TI - Role of a bulged A residue in a specific RNA-protein interaction. AB - The translational operator of the R17 replicase gene contains a bulged A residue that is essential for the specific binding to R17 coat protein. A large number of operator variants have been synthesized to more precisely examine the role of the bulged A residue on this specific protein-RNA interaction. By use of RNA ligase and transcription of synthetic DNA templates by T7 RNA polymerase, 14 different nucleotides were introduced to the bulged A position of three different coat protein binding fragments. The affinity between coat protein and each fragment was determined by a nitrocellulose filter binding assay. The data indicate that while functional groups on N1, C2, C6, N7, and 2'OH of the bulged A can be substituted without greatly changing protein binding, bulky substituents cannot be tolerated at these positions. Data from additional fragments that have base pair changes adjacent to the bulged A suggest that the propensity of the bulged A to intercalate into the helix can affect protein binding. PMID- 3327521 TI - Specificity of cotranslational amino-terminal processing of proteins in yeast. AB - Polypeptides synthesized in the cytoplasm of eukaryotes are generally initiated with methionine, but N-terminal methionine is absent from most mature proteins. Many proteins are also N alpha-acetylated. The removal of N-terminal methionine and N alpha-acetylation are catalyzed by two enzymes during translation. The substrate preferences of the methionine aminopeptidase (EC 3.4.11.x) and N alpha acetyltransferase (EC 2.3.1.x) have been partially inferred from the distribution of amino-terminal residues and/or mutations found for appropriate mature proteins, but with some contradictions. In this study, a synthetic gene corresponding to the mature amino acid sequence of the plant protein thaumatin, expressed in yeast as a nonexported protein, i.e., lacking a signal peptide, has been used to delineate the specificities of these enzymes with respect to the penultimate amino acid. Site-directed mutagenesis, employing synthetic oligonucleotides, was utilized to construct genes encoding each of the 20 amino acids following the initiation methionine codon, and each protein derivative was isolated and characterized with respect to its amino-terminal structure. All four possible N-terminal variants--those with and without methionine and those with and without N alpha-acetylation--were obtained. These results define the specificity of these enzymes in situ and suggest that the nature of the penultimate amino-terminal residue is the major determinant of their selectivity. PMID- 3327522 TI - Kinetic mechanism of DNA polymerase I (Klenow). AB - The minimal kinetic scheme for DNA polymerization catalyzed by the Klenow fragment of DNA polymerase I (KF) from Escherichia coli has been determined with short DNA oligomers of defined sequence. A key feature of this scheme is a minimal two-step sequence that interconverts the ternary KF.DNAn.dNTP and KF.DNAn+1.PPi complexes. The rate is not limited by the actual polymerization but by a separate step, possibly important in ensuring fidelity [Mizrahi, V., Henrie, R. N., Marlier, J. F., Johnson, K. A., & Benkovic, S. J. (1985) Biochemistry 24, 4010-4018]. Evidence for this sequence is supplied by the observation of biphasic kinetics in single-turnover pyrophosphorolysis experiments (the microscopic reverse of polymerization). Data analysis then provides an estimate of the internal equilibrium constant. The dissociations of DNA, dNTP, and PPi from the various binary and ternary complexes were measured by partitioning (isotope trapping) experiments. The rate constant for DNA dissociation from KF is sequence dependent and is rate limiting during nonprocessive DNA synthesis. The combination of single-turnover (both directions) and isotope-trapping experiments provides sufficient information to permit a quantitative evaluation of the kinetic scheme for specific DNA sequences. PMID- 3327523 TI - Specific proteolysis of native alanine racemases from Salmonella typhimurium: identification of the cleavage site and characterization of the clipped two domain proteins. AB - Native DadB and Alr alanine racemases (Mr 39,000) from Salmonella typhimurium are proteolyzed at homologous positions by alpha-chymotrypsin, trypsin, and subtilisin to generate in all cases two nonoverlapping polypeptides of Mr 28,000 and 11,000. Under nondenaturing conditions, chymotryptic digest results in an associated form of the two fragments which possesses 3% of the original catalytic activity, incorporates 0.76 equiv of the mechanism-based inactivator beta-chloro [14C]-D-alanine [Badet, B., Roise, D., & Walsh, C. T. (1984) Biochemistry 23, 5188], and exhibits a UV circular dichroism profile identical with that of native enzyme. Protein sequence analysis of the denatured chymotryptic fragments indicates the presence of a tetrapeptide interdomain hinge (DadB, residues 254 257; Alr, residues 256-259) that is attacked at both ends during proteolysis. Under the previously employed digest conditions, NaB3H4-reduced DadB holoenzyme is resistant to alpha-chymotrypsin and trypsin and is labile only toward subtilisin. These data suggest that the hinge structure is essential for a catalytically efficient enzyme species and is sensitive to active site geometry. The sequence at the hinge region is also conserved in alanine racemases from Gram positive bacteria. PMID- 3327525 TI - Catalytic mechanism and inhibition of tRNA (uracil-5-)methyltransferase: evidence for covalent catalysis. AB - tRNA (Ura-5-)methyltransferase catalyzes the transfer of a methyl group from S adenosylmethionine (AdoMet) to the 5-carbon of a specific Urd residue in tRNA. This results in stoichiometric release of tritium from [5-3H]Urd-labeled substrate tRNA isolated from methyltransferase-deficient Escherichia coli. The enzyme also catalyzes an AdoMet-independent exchange reaction between [5-3H]-Urd labeled substrate tRNA and protons of water at a rate that is about 1% that of the normal methylation reaction, but with identical stoichiometry. S Adenosylhomocysteine inhibits the rate of the exchange reaction by 2-3-fold, whereas an analogue having the sulfur of AdoMet replaced by nitrogen accelerates the exchange reaction 9-fold. In the presence (but not absence) of AdoMet, 5 fluorouracil-substituted tRNA (FUra-tRNA) leads to the first-order inactivation of the enzyme. This is accompanied by the formation of a stable covalent complex containing the enzyme, FUra-tRNA, and the methyl group of AdoMet. A mechanism for catalysis is proposed that explains both the 5-H exchange reaction and the inhibition by FUra-tRNA: the enzyme forms a covalent Michael adduct with substrate or inhibitor tRNA by attack of a nucleophilic group of the enzyme at carbon 6 of the pyrimidine residue to be modified. As a result, an anion equivalent is generated at carbon 5 that is sufficiently reactive to be methylated by AdoMet. Preliminary experiments and precedents suggest that the nucleophilic catalyst of the enzyme is a thiol group of cysteine. The potent irreversible inhibition by FUra-tRNA suggests that a mechanism for the "RNA" effects of FUra may also involve irreversible inhibition of RNA-modifying enzymes. PMID- 3327524 TI - Internal motions in yeast phenylalanine transfer RNA from 13C NMR relaxation rates of modified base methyl groups: a model-free approach. AB - Internal motions at specific locations through yeast phenylalanine tRNA were measured by using nucleic acid biosynthetically enriched in 13C at modified base methyl groups. Carbon NMR spectra of isotopically enriched tRNA(Phe) reveal 12 individual peaks for 13 of the 14 methyl groups known to be present. The two methyls of N2,N2-dimethylguanosine (m22G-26) have indistinguishable resonances, whereas the fourteenth methyl bound to ring carbon-11 of the hypermodified nucleoside 3' adjacent to the anticodon, wyosine (Y-37), does not come from the [methyl-13C]methionine substrate. Assignments to individual nucleosides within the tRNA were made on the basis of chemical shifts of the mononucleosides [Agris, P. F., Kovacs, S. A. H., Smith, C., Kopper, R. A., & Schmidt, P. G. (1983) Biochemistry 22, 1402-1408; Smith, C., Schmidt, P. G., Petsch, J., & Agris, P. F. (1985) Biochemistry 24, 1434-1440] and correlation of 13C resonances with proton NMR chemical shifts via two-dimensional heteronuclear proton-carbon correlation spectroscopy [Agris, P. F., Sierzputowska-Gracz, H., & Smith, C. (1986) Biochemistry 25, 5126-5131]. Values of 13C longitudinal relaxation (T1) and the nuclear Overhauser enhancements (NOE) were determined at 22.5, 75.5, and 118 MHz for tRNA(Phe) in a physiological buffer solution with 10 mM MgCl2, at 22 degrees C. These data were used to extract two physical parameters that define the system with regard to fast internal motion: the generalized order parameters (S2) and effective correlation times (tau e) for internal motion of the C-H internuclear vectors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327526 TI - Occurrence and significance of riboflavin deficiency in preterm infants. AB - Few studies have explored the importance of riboflavin deficiency in premature infants. Infants receiving human milk during the first 2 weeks become biochemically riboflavin-deficient, partly through photodegradation of riboflavin during the banking and delivery of human milk. Animal studies have shown that the metabolic lesions of riboflavin deficiency in sucking neonates differ in important ways from those seen later after weaning. Techniques are described for non-invasive study of functional riboflavin requirements by premature infants. It appears prudent to supplement human milk-fed babies with at least 300 micrograms riboflavin/day; but the potential danger of over supplementation in infants exposed to phototherapy is discussed. PMID- 3327527 TI - Vitamin D metabolism in preterm infants. AB - Perinatal metabolism of vitamin D was studied in premature babies with the aim of: (1) reporting the relationship between the pregnant mother and her preterm infant and the metabolism of vitamin D during the first weeks of life, and (2) assessing the effect of vitamin D metabolites on phosphorus calcium and magnesium intestinal absorption. There was only a positive correlation between plasma cord calcium and 25-hydroxyvitamin D levels and the mother's plasma levels at birth. During the hypocalcemic episode observed during the first week of life, vitamin D activation did occur, but later on rickets or osteomalacia cannot be due to the low levels of vitamin D metabolites in the preterm receiving an adequate dose of vitamin D (1,000-1,200 IU of D2). Calcitriol, the major metabolite of vitamin D, is acting on the intestine and promotes calcium absorption even in very tiny prematures. The pathogenesis of hypomineralization in the preterm infant is due to the low intake of calcium or phosphorus and/or poor absorption of calcium in the case of vitamin D deficiency. PMID- 3327528 TI - Effect of vitamin E substitution in very low birth weight infants. Active and inactive forms of vitamin E in plasma and red cells after moderate intramuscular supplementation. AB - Vitamin E supplementation was investigated in 38 very low birth weight infants after intramuscular substitution with two doses of 25 mg given on the 1st and 3rd day of life. Plasma and red cell concentrations of the biologically inactive tocopherol acetate and the active tocopherol were followed during the first month of life. Plasma levels of this substitution regime were compared with recent clinical studies. Although the applied dose was low in comparison to other studies, the levels obtained exceed the critical concentration of 12 microM which was reported to prevent retinopathy. Concentrations associated with side effects (84 microM) were found in nearly 50% of the babies but only for short duration (24 h). In more than 80% of the infants, biologically inactive tocopherol acetate was detected in plasma up to 1 day after substitution but not in red cells. PMID- 3327529 TI - Does diet in preterm infants influence clinical outcome? AB - After several decades of intensive research into feeding preterm infants, it is important to question why there is persisting uncertainty over their dietary management. The evolution of scientific investigation in this field is compared with that in other areas of clinical science, where a three-phase pattern emerges: phase 1, reports of anecdotal observation and clinical experience; phase 2, epidemiological observation and physiological experiment; and phase 3, controlled prospective trials of specific interventions on clinical outcome. It is argued that research into feeding preterm infants has not evolved beyond physiological experiment (phase 2) and that the absence of clinical outcome data (phase 3 research) explains major uncertainties in clinical practice. Data from a large randomized multicentre outcome study of preterm nutrition are used to demonstrate how the wealth of previous and current 'physiological' information cannot be used satisfactorily to predict desirable clinical outcome responses to early diet. PMID- 3327530 TI - Energy balance and composition of body weight. AB - Weight gain composition of growing very low birthweight (VLBW) premature infants can be assessed by a combined technique of nutrient balance and indirect calorimetry measurement. Both protein and energy intakes play an important role in the rate of growth and in the amount of non-protein energy (i.e. fat) storage. High energy intake is not always correlated with a higher rate of growth and can lead to high fat storage. PMID- 3327531 TI - Protein metabolism and postnatal growth in very low birthweight infants. AB - Due to the development of new 'bedside' investigative methods, relatively abstract physiologic concepts such as energy cost of growth, efficiency of protein gain, metabolic cost of protein gain and protein turnover have been quantified in very low birthweight infants. 'Healthy' premature infants expend about 30% of their energy to cover the metabolic cost of growth. Stable isotope techniques using 15N-(or 13C)-labeled amino acids gave a new insight into this very high energy demanding process represented by the protein accretion in growing tissues. It has been demonstrated that the rate of protein synthesis (10 12 g/kg/day) greatly exceeds that necessary for net protein gain (2 g/kg/day). The postnatal growth and protein metabolism have different characteristics in 'healthy', 'sick' or 'intrauterine undernourished' very low birthweight infants. PMID- 3327532 TI - New perspectives in neonatal nutrition. AB - Modern techniques of cardiopulmonary life support, particularly for very low birthweight infants and those suffering from major surgical conditions, has presented the neonatologist with a completely new population of infants for whom continued survival and further normal physical and mental growth and development are critically dependent on adequate nutrition. The uncertainties surrounding the definition of 'adequacy' as well as the techniques and difficulties of its attainment and assessment are exposed. This paper examines desirable goals to be aimed for in the nutrition of the neonate in relation to genetic potential for growth, development and body composition. There is discussion of current research into the intermediary metabolism and utilisation of macronutrients and certain minerals for energy production and tissue growth and of methodology for determining body composition. The editor has also allowed a certain licence for speculation concerning future directions in neonatal nutrition. PMID- 3327533 TI - Significance of plasma amino acid pattern in preterm infants. AB - Nutritional studies frequently take into consideration plasma amino acid concentrations in order to evaluate the adequacy of protein intake in preterm infants. From our data of more than 100 determinations of plasma amino acid concentrations in preterm infants, we review the factors influencing the aminogram. Method and moment of sampling, protein intake and composition, protein turnover rate, energy supply, and gestational age, all may influence plasma amino acid concentrations. It is suggested that the cord blood amino acid concentration may be considered as an appropriate value of reference and a safe level for growing preterm infants. PMID- 3327534 TI - Lipid metabolism in premature infants. AB - Fats provide 40-50% of the total calories in human milk or infant formula. The milk secreted by mothers of preterm infants differs in fat composition from that of mothers of full-term infants in having higher levels of medium chain fatty acids (C12, C14) throughout the first 3 months of lactation, and higher levels of long chain polyenoic fatty acids during the first 3 months of lactation. These differences in composition benefit the preterm infant by providing higher levels of rapidly absorbed medium chain fatty acids and long chain polyenoic fatty acids needed for brain development. Fat digestion: The low levels of pancreatic lipase and bile salts in the preterm infant are compensated for by lipolysis in the stomach by lingual and gastric lipase and by the intestinal hydrolysis of fat through the action of human milk bile salt-stimulated lipase. Fat digestion is efficient in the preterm infant who absorbs about 80-90% of ingested fat. Lipid clearing from the circulation depends upon the activity of the enzymes lipoprotein lipase, hepatic lipase, and lecithin-cholesterol acyltransferase. The activity of these enzymes is lower or equal to that of term infants, depending upon the degree of prematurity and the nutritional regimen, especially in parenterally fed infants. PMID- 3327536 TI - Taurine and the premature. AB - In the human fetus and in the early postnatal period, during development, the total body taurine content, particularly of the brain, increases markedly. It can be estimated that the human fetus accumulates approximately 50-60 mumol/24 h during the last 4 weeks of pregnancy. As there is evidence for the relative inability of infants to synthesize taurine, this nitrogen compound has to be wholly supplied by the mother during pregnancy and by diet after birth, particularly for the prematures who have to constitute appreciable reserves in their tissues. In adults (mammals and humans), it has been shown that the slowly exchangeable pool of taurine (mainly brain and muscles) cannot be increased by exogenous taurine but, in growing mammals, taurine from diet is rapidly transferred to tissues. Although no real proof yet exists, it seems probable that taurine should be considered an essential nutrient for premature infants. PMID- 3327535 TI - Carnitine and the premature. AB - After birth, the main energy fuel for the newborn is constituted by fat. Carnitine is necessary for the beta-oxidation of long chain fatty acids at the mitochondrial level, and seems also to have a role in the metabolism of the branched-chain amino acids, in ammonia detoxification, and in urea production. Colostrum is particularly rich in carnitine whereas semi-elemental formulae and soy-based formulae contain little or no carnitine. Since the newborn has a low capacity for carnitine biosynthesis, it seems useful to administer L-carnitine to infants on total parenteral nutrition, soy-based or semi-elemental formulae. PMID- 3327537 TI - Stable isotope tracers and the determination of fuel fluxes in newborn infants. AB - After birth, newborns adapt from the in utero situation of a continuous fuel supply to the postnatal situation of feeding and fasting periods. In order to maintain adequate fluxes of energetic substrates to their various organs and tissues, neonates must rapidly activate the release of glucose, free fatty acids and ketone bodies into the blood stream. This review will summarize some of the techniques and results available today regarding the in vivo kinetics of an energetic substrate in early postnatal life: the rate of production of this substrate, the overall rate of its uptake by the tissues, its rate of oxidation and contribution to the total caloric demand, the rate of conversion of a precursor into this substrate. PMID- 3327538 TI - Vitamins and the premature. AB - Vitamins are organic compounds essential in small amounts for metabolic functions. Since they cannot be synthesized in the body they must be supplied with the diet. While fat-soluble vitamins cross the placenta by single and/or facilitated diffusion the water-soluble vitamins are actively transported with the exception of vitamin C. An adequate supply of fat-soluble vitamins to the fetus seems to be dependent on maternal blood levels during gestation. On the contrary, the transfer of water-soluble vitamins is relatively independent of the levels in maternal blood. Due to their immaturity preterm and low birth weight infants require higher dosages of some vitamins compared to healthy full-term newborns. PMID- 3327539 TI - Hormonal effects of lead acetate in the male rat: mechanism of action. AB - Environmental exposure to toxic levels of lead occurs in a number of industries with potential adverse effects on the reproductive capacity of exposed men. Using a rat model, we previously reported that dietary exposure to lead resulted in suppressed spermatogenesis and testosterone levels without significant changes in luteinizing hormone (LH). In this study, to identify more specifically the site of lead's toxic actions on the hypothalamic-pituitary-testicular axis, the response of lead-treated male rats as compared to control animals to naloxone, gonadotropin-releasing hormone (GnRH), and LH stimulation was studied. Three groups of 52-day-old Wistar rats were allowed access to either deionized distilled water containing no lead acetate or a 0.3% lead acetate solution for 30 days. In each study group, 10 control and 10 lead-treated animals were anesthetized prior to cardiac puncture and collection of serum for the measurement of lead level and baseline LH (Groups I and II) or testosterone levels (Group III). In Group I, 20 min after an i.p. injection of naloxone (1.5 mg/kg/BW), the animals were killed by decapitation, and serum was collected for LH measurement. Thirty minutes after an i.p. injection of GnRH (100 ng/100 gm BW), Group II animals were killed by decapitation, and serum was collected for LH. Sixty minutes after an injection of LH (100 mg/100 mg BW), serum was collected from Group III animals for testosterone measurement. All control animals and lead-treated animals consumed similar volumes of water. Control animals had undetectable levels of lead in their blood. Lead-treated animals had mean blood lead values of 30 micrograms/dl +/- 5 micrograms/dl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327540 TI - In-vitro pulsatile luteinizing hormone-releasing hormone output is dependent on hypothalamic region and the stage of the estrous cycle. AB - In the following experiments, the role of the preoptic-suprachiasmatic area (POA SCN) in the control of luteinizing hormone-releasing (LHRH) release was examined by in vitro superfusion of either mediobasal hypothalamus (MBH) or MBH-POA-SCN fragments obtained from cycling rats killed on various days of the estrous cycle. The lowest level of LHRH output occurred during estrus, highest levels during diestrus, and intermediate levels on proestrus in the MBH-POA-SCN preparation. As expected, significant decreases in LHRH output from the MBH alone occurred during both days of diestrus and on proestrus, as compared to output from the MBH-POA SCN tissue, since this structure contains most of the LHRH perikarya. However, similar LHRH secretion patterns were detected in estrus from both preparations. The average period of the LHRH pulses for the estrous cycle in the MBH-POA-SCN was 30.9 +/- 1.2 min compared to 97.7 +/- 25.1 min in the MBH, with significant differences occurring on diestrus 2. The increase and extreme variability of the period of LHRH pulses in the MBH region, compared to the MBH-POA-SCN region, suggests that it is the latter region that contains the neural circuits that control the LHRH pulse generator. The LHRH pulse amplitudes from both hypothalamic regions were similar during all phases of the estrous cycle, except diestrus 2, when the LHRH pulse amplitude from the MBH region was significantly lower than the LHRH pulse amplitude from MBH-POA-SCN. The percentage of LHRH released in the MBH did not vary with the estrous cycle, however, in the MBH-POA SCN significant changes were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327541 TI - Neurophysin in the large luteal cell of the nonpregnant water buffalo (Bubalus bubalis): immunohistochemical localization. AB - Light microscopy immunohistochemistry was used to localize neurophysin in the corpus luteum of the mid-luteal phase of the estrous cycle of the water buffalo (Bubalus bubalis). Corpora lutea weighing 0.39-0.65 g from a recent ovulation showed no staining. Corpora lutea identified with the late luteal phase showed only weak evidence of staining. The neurophysin staining was confined to a specific region of large oval-shaped cells (20-30 microns diameter), which had a very eosinophilic cytoplasm. The intense localization of staining to a distinct area of the cytoplasm was previously only observed in the corpus luteum of the cow. Corpora lutea obtained from all quadrants of pregnancy did not stain. Controls in which the neurophysin antiserum was substituted with serum from an unimmunized rabbit (normal rabbit serum) or neurophysin antiserum preabsorbed with bovine oxytocin-associated neurophysin I also did not stain. These data indicate the neurophysin is present in the mature corpus luteum of the nonpregnant water buffalo as it is in other nonpregnant ruminants, the ewe and cow. PMID- 3327542 TI - Prostacyclin stimulates relaxin release from cultured porcine luteal cells. AB - The release of relaxin from cultured porcine luteal cells (derived from pregnant sows) was detected by a reverse hemolytic plaque assay. In this assay, luteal cells are cocultured in monolayers with protein-A-coupled ovine erythrocytes. In the presence of porcine relaxin antiserum and complement, a zone of hemolysis--a plaque--develops around relaxin-releasing luteal cells. Treatment with a prostacyclin analogue (carba-prostacyclin; 10 and 100 ng/ml) significantly accelerated the rate of plaque formation in a dose-dependent manner. In contrast, the culture of luteal cells in the presence of cyclooxygenase inhibitors (indomethacin, ibuprofen, and diclofenac sodium) resulted in no change in the rate of basal relaxin release. These results add weight to the view that prostacyclin may contribute alone, or perhaps in combination with other prostanoids, to the overall regulation of ovarian endocrine function and relaxin release during pregnancy in the pig. However, the data are inconsistent with the possibility that prostacyclin arises from relaxin-releasing luteal cells themselves. PMID- 3327543 TI - Immunocytochemistry of extracellular matrix in the lamina propria of the rat testis: electron microscopic localization. AB - The distribution of laminin, type IV collagen, heparan sulfate proteoglycan, and fibronectin was investigated in the rat testicular lamina propria by electron microscopic immunocytochemistry. Distinct patterns were observed for each antigen within the extracellular matrix (ECM) layers of the lamina propria. Laminin, type IV collagen, and heparan sulfate proteoglycan all localized to the seminiferous tubule basement membrane. Type IV collagen and heparan sulfate proteoglycan, but not laminin, localized to the seminiferous tubule side of the peritubular myoid cells. All four of the antigens were localized between the peritubular and lymphatic endothelial cells. Failure to localize fibronectin in the ECM layer between the Sertoli and peritubular myoid cells tends to support the concept that adult Sertoli cells do not produce this protein in vivo. Intracellular immunostaining was insufficient to allow unambiguous identification of the cellular source of any of the ECM molecules. PMID- 3327544 TI - Detection of relaxin by immunohistochemistry in the corpus luteum during lactation. AB - The occurrence of relaxin in corpora lutea (CL) throughout lactation was studied in rats and pigs using the avidin-biotin immunoperoxidase procedure and homologous antisera to purified relaxins. In the rat, both CL from the previous pregnancy (CLp) and CL formed after postpartum ovulation, termed CL of lactation (CLL), were studied. In the rat, relaxin was localized only in cells of the CLp in early lactation, and immunostaining declined with advancing lactation. In late lactation (Days 16-20), immunoreactive relaxin first appeared in cells of the CLL, although the intensity was less relative to that observed in the CLp in early lactation. Cells of the CLp were sensitive to the effects of exogenous prostaglandins (PG) as shown by a loss of relaxin immunostaining at both 12 and 48 h after a PGF2 alpha challenge. In the sow, the CLp showed highest immunostaining in early lactation with a gradual reduction as lactation progressed, such that by Day 20 lactation, immunostaining was lost. These localization studies show that immunoreactive relaxin is present in the CL during lactation. Low levels of relaxin localized in the CLL of late lactation in the rat probably represents newly formed hormone, whereas the immunostaining in the CLp of the pig and rat appears to be residual relaxin and an indicator of the degeneration of the CLp with advancing lactation. PMID- 3327545 TI - Localization of a pore-forming protein (perforin) in granulated metrial gland cells. AB - Several studies have suggested that the granulated metrial gland (GMG) cells of the metrial gland (MG) may be natural killer (NK)-like cells. The cytotoxicity of NK cells involves secretion of a pore-forming protein termed perforin, which can polymerize on the target cell membrane to form transmembrane pores that are thought to be involved in target cell death. In the present study, we used an antiserum against perforin to determine whether this protein can be detected immunohistochemically in GMG cells. Mouse uteri were fixed by vascular perfusion with several fixatives on Day 14 of pregnancy, and tissue sections were labeled by an indirect immunofluorescence method. Specific perforin labeling was detected in GMG cells throughout the MG, in the decidua basalis, and in the labyrinthine placenta. The presence of perforin in GMG cells supports the suggestion that they may be NK-like cells. PMID- 3327546 TI - [Problems posed by the morphologic demonstration of estrogen receptors]. AB - The different morphological methods that can be used to detect and localize estrogen receptors into the cell are reviewed. Sex steroid receptors measurements are useful for clinicians and studies on breast cancer demonstrated their predictive value in the management of patients. Beside the routinely used radiochemical assay, morphological detection of receptors can be realized by two different ways: an indirect way, using markers of estrogen and its detection when linked to the receptor. One can use radioactive estrogen and autoradiography; fluorescent estrogen and U-V microscope; or anti-estrogen antibody linkage and immunocytodetection. All these methods face two complex problems: the large diffusibility of steroid hormone and their affinity for many other ligands than their specific receptor; a direct way, irrespective of the presence or absence of hormone, using a monoclonal antibody generated against receptor protein from human breast cancer. Using this antibody, estrogen receptors are strictly localized into the nuclei of cells (no cytoplasmic localization). This appears to be the best morphological method and a useful complement of radiochemical assay. PMID- 3327547 TI - [Development of the curvature of the cervical spine in utero. Attempted interpretation]. AB - It is conventional saying that the fetal rachis shows only one ventral concavity. An echographic study allowed to observe in utero the rachis of more than a hundred live fetuses. The radius of this curvature gradually increases according to the development, revealed by the disappearance of the cervical curvature under the influence of the weight of the head and the uterine constraints. The sagittal curvatures of the vertebral column explains mans adaptability to the erected position. The authors think that the conventional conception, in which ontogenetic development is comparable with phylogenetic development, needs to be reconsidered: the cervical curvature is a prime curvature setting the evolutionist question about the origins of the rachidian curvatures. PMID- 3327549 TI - The lymphomas. Histopathology and immunobiology. PMID- 3327548 TI - [Isolated azygos continuation of the inferior vena cava. (Absence of the retrohepatic segment of the inferior vena cava)]. AB - The isolated azygos continuation of the inferior vena cave is a very rare variation of this organ. It is accompanied by the absence of the retrohepatic segment of the vena cava with two new observations, the literature is revised and the origin discussed. PMID- 3327550 TI - Treatment of Hodgkin's disease. PMID- 3327551 TI - Follicular non-Hodgkin's lymphoma. AB - FL is usually widely disseminated at presentation and responds to radiotherapy, single agent chemotherapy and combination therapy. The disease pursues a remitting and relapsing course with continuing sensitivity to brief periods of treatment until a terminal phase of drug resistance, transformation, or bone marrow failure is reached. Newly recognized prognostic factors indicative of tumour bulk include hepatosplenomegaly, B symptoms, anaemia and abnormal liver function. Using these factors it is possible to identify those patients at first diagnosis for whom conservative management is appropriate and those with a much less favourable prognosis for whom experimental treatments are being investigated. PMID- 3327552 TI - Management of high-grade non-Hodgkin's lymphoma in adults. PMID- 3327553 TI - Preserving fertility in Hodgkin's disease. PMID- 3327554 TI - Second malignancy in lymphoma. PMID- 3327555 TI - Special aspects of treatment of paediatric lymphomas. PMID- 3327556 TI - Multicentre studies and the treatment of lymphomas. PMID- 3327557 TI - Epidemiology of the lymphomas in the United Kingdom: recent developments. AB - A discussion of the difficulties associated with classification of the lymphomas, particularly by subtype, precedes the descriptive epidemiology of the disease. Recent data collected in the United Kingdom and Yorkshire are presented to illustrate demographic features and variations in lymphoma incidence, both in relation to certain time periods and geographical distribution. Lymphoma aetiology is addressed in the light of current epidemiological approaches, using as an example data from a Yorkshire based case-control study. Three broad areas of aetiological significance--genetics, viruses and immunity--form the bases for presenting descriptions of known or suspected aetiological factors associated with Hodgkin's disease and non-Hodgkin's lymphoma. The final overview points the way to relevant future research. PMID- 3327558 TI - The radiology of lymphoma. AB - The development of new imaging techniques over recent years has improved the accuracy with which the extent of the disease can be demonstrated in patients with lymphoma. These methods either complement or replace existing conventional radiological methods such as plain films, bariums, intravenous urograms or lymphography. CT in particular, and to a lesser extent ultrasound and radionuclides, now plays an important part in helping the clinician to manage patients with lymphoma. It is impractical and unnecessary to use all available imaging studies. More than ever, close co-operation between the clinician and radiologist is essential to derive the maximum amount of information from the studies and to use the techniques effectively and appropriately. This chapter has reviewed the advantages and limitations of each imaging method, stressing the role of each in staging the lymphomas and in monitoring response to treatment. The common radiological appearances of the effects of lymphoma on each organ system have been described. The possible contribution that other techniques may make in the future has been discussed. PMID- 3327560 TI - Rheology of the absolute polycythaemias. AB - The absolute polycythaemias include all patients who have a raised red cell mass. They may be divided by clinical and laboratory investigation into: primary proliferative polycythaemia (polycythaemia rubra vera), secondary polycythaemias, and idiopathic erythrocytosis. In vitro, the PCV is the single most important determinant of whole blood viscosity with the most marked effects at low shear rates. Yield stress is also dominantly influenced by PCV. Thus in the absolute polycythaemias, from whatever cause, whole blood viscosity and yield stress are high. However, flow conditions in vivo are much more complex than those usually used in in-vitro measurements. Under normal physiological conditions, whole blood viscosity probably does not determine flow in vivo. The observed in-vitro changes are only of relevance in vivo when local or general abnormalities of flow occur. In primary proliferative polycythaemia (PPP) and idiopathic erythrocytosis, presentation with ischaemia or thrombosis (either arterial or venous) is common, and the cerebral circulation is at particular risk. The incidence of vascular occlusion is positively correlated with the PCV. There is an inverse correlation between PCV and cerebral blood flow (CBF), with untreated patients having low CBF values. This is probably a 'physiological' change related to the increased oxygen carrying capacity at high PCV values. However, in many patients, cerebral oxygen carriage actually increases on reduction of the PCV to normal. This explains the improvement in cerebral ischaemic symptoms and mental performance which may be observed following treatment. Platelet contact and adhesion to the vessel wall are increased at high PCV values and, combined with the lower blood flow in both the arteries and veins, tend to favour thrombus formation. Ischaemia causes vessel dilatation but when this is maximal the high whole-blood viscosity demonstrated in vitro is a major determinant of flow. Hence in man and experimental animals, as demonstrated in the brain, the area of ischaemia or non perfusion following arterial occlusion is greatest at high PCV values. Patients with polycythaemia due to hypoxic lung disease have a poor prognosis. The hypoxic pulmonary vasoconstriction combined with the high blood viscosity causes an increase in pulmonary vessel resistance. PCV reduction of 0.50-0.52 leads to an improvement in work performance and mental alertness, and reduction in pulmonary vascular resistance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327559 TI - Blood rheology in vitro and in vivo. AB - Blood rheology tests are traditionally used for detection of organic disease and for monitoring disease activity. More recently they have been used for prediction of blood flow in vivo, not only in overt hyperviscosity syndromes but also in the covert hyperviscosity of low-flow states. The traditional ESR test result increases with red cell aggregation induced by increases in large, asymmetrical plasma globulins. However, small increases in haematocrit and large increases in plasma viscosity each decrease the ESR, reducing both its diagnostic utility and its ability to predict blood flow in vivo. The ESR should be corrected to a standard haematocrit, or else replaced by the ZSR or plasma viscosity, which are more rapid, simple, sensitive and independent of haematocrit. For prediction of blood flow in vivo, these tests can be supplemented by measurement of whole-blood viscosity, which can be performed simply and cheaply in capillary viscometers at high shear rates. Whole-blood viscosity is determined by plasma viscosity, haematocrit and red cell deformability at high shear rates. Its measurement is useful in overt hyperviscosity syndromes, particularly in estimating the effect of red cell transfusion in anaemic patients with plasma hyperviscosity, hyperleukocytic leukaemias or sickling disorders. Blood viscosity should be related to the haematocrit or haemoglobin concentration in order to estimate oxygen delivery to tissues. Changes in blood viscosity can be compensated readily in the normal circulation but not in the compromised, low-flow circulation. In these circumstances, systemic increases in plasma viscosity, haematocrit, whole blood viscosity, red cell aggregation and in the numbers of circulating rigid red or white blood cells can perpetuate low-flow states and ischaemia. Red cell deformability in narrow vessels is best measured by micropore filtration systems, in which the effect of white cells has been eliminated. Red cell deformability is reduced by change in shape, decrease in the ratio of surface area to volume, decreased membrane flexibility and increased internal viscosity (MCHC and inclusions). White cells have negligible effects on bulk-blood viscosity but have important effects on blood flow in narrow vessels, due to their high internal viscosity and their adhesiveness when activated. White cell filterability is lowest for monocytes and for activated granulocytes and these adhesive and rigid cells may have important effects on microcirculatory blood flow in low-flow states. PMID- 3327561 TI - The contracted plasma volume syndromes (relative polycythaemias) and their haemorheological significance. AB - Relative polycythaemia is a general term which includes patients with a normal red cell mass but a contraction of the plasma volume as the cause for the polycythaemia. The relative polycythaemias can broadly be divided into two groups. Firstly, relative polycythaemia may be due to a primary loss of plasma volume due to dehydration, capillary leak or hypo-oncotic pressure. Secondly, relative polycythaemia may be due to a primary contraction of the vascular compartment (i.e. reduced venous compliance). It is this second group which is the least understood and is analysed in detail in this review. In general, this group of polycythaemias is secondary to exogenous or endogenous stress and is mediated via the sympathetic nervous system. Hypoxia, smoking, neurological disorders, myocardial infarction and acute psychological stress have all been demonstrated as possible factors. In many cases of chronic stress polycythaemias aetiological factors may be identified, whereas in others the term idiopathic is probably appropriate. There appears to be a relationship between the idiopathic stress polycythaemias, hypertension and psychological stress. Other patients may have primarily a disorder of blood volume control involving the autonomic nervous system and its receptors. The haemorheological significance of relative polycythaemia and its management are discussed. Treatment is generally dictated by the underlying cause. In stress polycythaemias the stimulus should be removed as far as possible. However, in some patients with chronic idiopathic stress polycythaemia, regular venesection may be required to maintain the venous haematocrit at an appropriate level. PMID- 3327562 TI - Rheology of paraproteinaemias and the plasma hyperviscosity syndrome. AB - The proper understanding of the causes, pathophysiology, diagnosis and management of the plasma hyperviscosity syndrome is based on good knowledge of malignant paraproteinaemias, properties of immunoglobulins, rheology of blood in the microcirculation, and modern plasma separation techniques. This multifaceted syndrome complicates less than ten per cent of IgA and IgG myelomas, and up to one-third of Waldenstrom's macroglobulinaemias. A few cases of HVS have also been reported in association with polyclonal hypergammaglobulinaemias. Excessive paraproteinaemia may cause the plasma HVS, especially when paraproteins are extraordinarily large, asymmetrical or cryosensitive, or if they aggregate into hyperviscous macroaggregates. The resultant severe microcirculatory impairment is mainly due to the combined effects of plasma hyperviscosity, significant plasma volume expansion and intense red cell aggregation. The individually variable general symptoms, bleeding tendency, ocular, neurological, cardiovascular, and renal manifestations and laboratory parameters of the HVS are summarized briefly. The majority of patients present hyperviscosity manifestations when the plasma viscosity exceeds 5-6 mPa.s. Plasmapheresis or plasma exchange have established themselves as efficient and safe modes of therapy of hyperviscosity and hypervolaemia. The therapeutic guidelines for the plasma HVS are briefly discussed with regard to recent experience with developing plasma separation techniques. Diagnostic and therapeutic advances combined with increasing haemorheological knowledge have greatly improved the proper management of this potentially lethal complication of paraproteinaemias. PMID- 3327563 TI - Hyperleukocytic leukaemia: rheological and clinical features and management. PMID- 3327564 TI - Rheology of the sickle cell disorders. AB - The sickling process causes secondary changes in cell shape, size, cation and water content, and membrane structure that contribute to the impairment of intrinsic cell deformability (Figure 2). This rheological defect is partially compensated by a low haematocrit, which moderates the rise in whole-blood viscosity, and by a rise in cardiac output which increases capillary flow velocity (Berger and King, 1982). A delicate balance exists between these mechanisms and any local disturbance of this balance by pathological changes in factors extrinsic to the sickle cell (Figure 2) can precipitate vaso-occlusion. There is still considerable controversy over the site (arteriolar, capillary, or venular) of vaso-occlusion, the type of sickle cell (reversibly sickled or irreversibly sickled) that is primarily involved, and the relative importance of extra-erythrocytic precipitating factors such as stasis, hypoxia, hyperosmolality, acidosis, alteration in temperature, acute-phase rise in plasma proteins and leukocytes, prothrombotic changes in coagulation factors and platelets, and adhesion of blood cells to vascular endothelium (Figure 2). A low grade hypercoagulable state has been described in patients with SS (Leichtman and Brewer, 1978; Richardson et al, 1979) which may be related to the procoagulant effect of the shift of phosphatidyl serine to the outer lipid bilayer of the sickle cell (Chiu et al, 1981; Franck et al, 1985). Platelets appear to accumulate at sites of vaso-occlusion (Siegel et al, 1985) and their migration to the vessel wall may be enhanced by the presence of poorly deformable erythrocytes (Aarts et al, 1984). Endothelial cell damage in the arterial or venous circulation may also contribute (Klug et al, 1982). Thus vaso-occlusion appears to result from a complex interaction between blood cells, plasma proteins and endothelium and any one of several precipitating factors may disturb the fragile steady state and cause a painful crisis. The study of sickle cells by rheological methods has considerable potential for investigating the pathophysiology of vaso occlusive episodes in the SCD and for monitoring, both in vitro and ex vivo, the efficacy of antisickling compounds. Because of the multiple intrinsic and extrinsic factors that contribute to the rheological defect, it is not yet known which of these should be the primary target for an antisickling agent. In-vitro rheological studies in which different metabolic stresses can be applied to intact sickle cells in the presence of a putative antisickling drug should help to answer this question.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327565 TI - Blood rheology and pregnancy. AB - Pregnancy is a hypervolaemic situation with early expanded plasma volume, a high cardiac output and a decrease in the vascular and rheological resistance. The increase in plasma volume correlates better with fetal size than maternal size. The hypervolaemic and vasodilated state that accompanies normal pregnancy results in a high flow in the uterine arteries. In contrast, patients with PIH (pregnancy induced hypertension) or placental insufficiency may have a contracted plasma volume secondary to diffuse vasoconstriction. In spite of the intense vasospasm and hypovolaemia, pre-eclampsia has generally a cardiac output which may be equal, higher or lower compared with non-eclamptic pregnancy. Hypovolaemia is reflected in a higher haematocrit than normal. In the case of a hypovolaemic state, haemoconcentration is associated with high red cell aggregation. In fetal distress and severe PIH, the rheological status (haemoconcentration and elevated red cell aggregation) has a high predictive value for perinatal complications. In patients with severe PIH, erythrocyte filtration is impaired. The increased leukocyte count in patients with PIH may occlude small vessels and could be a factor impairing intervillous blood flow. The increased erythrocyte rigidity may result from a re-distribution of cellular calcium metabolism (Blaustein concept). We conclude that there is an optimal haematocrit during pregnancy between 30% and 38%. The presence of a high haematocrit and in addition elevated red cell aggregation should alert the physician to an increased risk of fetal compromise. PMID- 3327566 TI - Blood rheology in the newborn infant. AB - The blood in neonates shows several peculiar properties which affect its rheological properties. 1. The haematocrit in neonates may be as high as 0.65 l/l without any clinical signs. 2. Both plasma viscosity and red cell aggregation are markedly lower in neonates than in adults because of low protein levels in neonates. This results in decreased blood viscosity at given haematocrit, particularly at low shear forces. 3. Deformability of neonatal red cells is similar to that of adult cells when studied under controlled conditions (e.g. rheoscope, ektacytometer). However, neonatal red cells are less filterable and require higher pressures for entering narrow micropipettes than adult red cells due to the larger size of neonatal red cells. 4. Neonatal leukocytes require higher pressure for the passage of 5 microns filter pores or 5 microns micropipettes than adult cells. The following haemorheological disorders have been observed in neonates: 1. Polycythaemia in infants with late cord-clamping, severe asphyxia, growth retardation and diabetic mothers. 2. Markedly decreased red cell deformability in septicaemia, necrotizing enterocolitis and in vitamin E deficiency (after exposure to oxidizing agents). 3. Moderately decreased red cell deformability in infants with diabetic mothers, growth retardation and severe acidosis. 4. Increased red cell aggregation in septicaemia. 5. Lack of red cell aggregation in immature neonates. 6. Decreased ability of leukocytes from septic neonates to pass filter pores and micropipettes. Treatment may be either haemodilution (in polycythaemia) or exchange transfusion (in septicaemia and necrotizing enterocolitis). Haemorheological drugs have not been used in neonates. PMID- 3327567 TI - Blood rheology in general medicine and surgery. AB - Traditionally, blood rheology tests have been used in diagnosis and monitoring of infection, rheumatic diseases and malignancy, and are still of clinical value in these conditions. In the last twenty years, clinical and epidemiological studies have shown that the haematological determinants of blood flow resistance (haematocrit, fibrinogen, white cell count and altered red and white cell rigidity) are also associated with nutritional, metabolic, endocrine and vascular disorders. Decreased red cell deformability may contribute to reduced red cell survival and anaemia in burns, malaria, liver disease and kidney failure. In trauma and inflammatory disease, overt hyperviscosity is usually prevented by vasodilatation and reduction in the haematocrit. However, low-flow states may arise systemically from haemoconcentration (contracted plasma volume, Chapter 3) in severe burns, inappropriate red cell transfusion, or dehydration due to illness; systemically in circulatory shock; and locally in venous thrombosis or arterial disease. In such circumstances, the intrinsic flow resistance of blood may perpetuate flow disturbance, ischaemia and thrombosis. Conversely, optimal levels of haematocrit, fibrinogen and white cell count may be lower than normal in low-flow states. Haemodilution by colloid infusion is beneficial in burns, shock, major surgery, prevention of postoperative venous thrombosis, chronic stable claudication and possibly in acute stroke and retinal vein thrombosis. Plasma exchange may be beneficial in severe Raynaud's phenomenon. Defibrination with ancrod is effective in prevention and treatment of venous thrombosis but its role in arterial disease is unproven. The benefits of streptokinase therapy in venous thrombo-embolism and acute myocardial infarction may be partly rheological, due to fibrinogen depletion. Drugs with rheological effects may be beneficial in intermittent claudication. PMID- 3327568 TI - Tropical myelopathies and myeloneuropathies. PMID- 3327569 TI - The Wallace memorial lecture, 1986. Is it new? PMID- 3327571 TI - Preparation for blood group-incompatible bone marrow transplantation: comparison of two techniques. AB - Two similar techniques of red cell depletion of blood group-incompatible marrow prior to bone marrow transplantation were compared in 8 patients. The first method involved a single sedimentation step and removed a mean of 91% of marrow red cells and 33% of marrow nucleated cells. The second method involved multiple sedimentation steps and removed a mean of 96% of red cells and 29% of nucleated cells. Both methods can be recommended to a transfusion service newly involved in a bone marrow transplantation program. PMID- 3327570 TI - Autoantibodies in 16 patients with extensive burns and a review of the literature. AB - Serum samples were taken during the first 3 weeks and 1 year after discharge from hospital of 16 patients with burns covering more than 35 per cent of the body surface area. The sera were tested for the presence of antinuclear, antimitochondrial, anti smooth muscle, anti brush border and anti gastric parietal cell autoantibodies using the technique of indirect immunofluorescence. Compared with measurements for the same autoantibodies, in sera from 25 healthy blood donors, the burned patients' sera showed the presence of anti smooth muscle autoantibodies in 81.2 per cent, anti brush border autoantibodies in 56.2 per cent, antimitochondrial autoantibodies in 31.2 per cent and antinuclear autoantibodies in 12.5 per cent of the sera. Autoantibodies to gastric parietal cells were not detected. A correlation was noted between the presence of antimitochondrial autoantibodies and alterations in liver function. In contrast, no correlations were found between the raised levels of the various autoantibodies and resuscitative fluid or antibiotic therapy, intercurrent infections, serum immunoglobulin levels, surgical treatment or the duration of stay in hospital. The high titre of autoantibodies to anti smooth muscle could have arisen from tissue protein degradation associated with the raised requirements for energy by the hypermetabolic patients. PMID- 3327572 TI - Applications of immunocytochemistry to clinical cytology. AB - This article reviews the recent studies reporting the applications of immunocytochemistry to diagnostic problems in clinical cytology. A series of studies with monoclonal antibody (MAb) B72.3 is discussed in detail. MAb B72.3, reactive with a high molecular weight, glycoprotein, tumor-associated antigen, designated TAG-72, has been shown previously to be reactive with formalin-fixed, paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon, and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct to diagnose carcinoma in cell block and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from the majority of patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected tumor cells in effusion specimens from most of the patients with "non-small cell" carcinoma of the lung and with carcinoma of the ovary. MAb B72.3 was also used with fine needle aspiration biopsies (FNABs) and corresponding surgically excised tumors to determine cellular reactivity. Positive staining with MAb B72.3 was observed in needle aspirates of the great majority of "non-small cell" carcinomas of the lung, adenocarcinomas of the breast, adenocarcinomas of the colon, and carcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, sarcomas, and glial tumors stained negatively with the antibody. Most benign lesions from the breast, lung, pancreas, parotid, and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B723. In more than 90% of these patients, the staining patterns of tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, is most selectively expressed in carcinomas, and may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in FNABs. PMID- 3327573 TI - Perioperative blood transfusion and solid tumor recurrence--a review. AB - Evidence regarding the association of blood transfusions with recurrence of solid tumors is largely conflicting. This is perhaps not surprising given the retrospective nature of the studies, the complexity of the disease and its treatment, and variations in local transfusion practices. Nonetheless, data demonstrating that transfusions of whole blood are associated with earlier cancer recurrence are most readily explained by a cause and effect relationship. There is a growing literature documenting previously unforeseen immunologic consequences of homologous blood transfusion. These possible clinical consequences may include earlier cancer recurrence, and increased susceptibility to infection with bacteria and viruses. The questions raised in this review will likely be answered by further studies. For the present, the prudent clinician will select red blood cells rather than whole blood for transfusion, and recognize that blood transfusion is a therapy with considerable benefits, but also considerable risks. PMID- 3327574 TI - Angioimmunoblastic lymphadenopathy: comprehensive review. PMID- 3327576 TI - [Subgingival access in fixed prosthetics: tissue consequences, guiding of healing]. PMID- 3327575 TI - [A case of portal system gas]. PMID- 3327577 TI - [Large provisional restorations: occlusal aspect]. PMID- 3327578 TI - [Implementation of the equipoise clasp]. PMID- 3327580 TI - When doctors went to war. PMID- 3327581 TI - War ended decades ago but PoWs' problems continue. PMID- 3327582 TI - [Activity of the Slovak Medical Society 1981-1986]. PMID- 3327579 TI - Hypogammaglobulinemia: therapeutic rationale. AB - Hypogammaglobulinemia is a feature of several B-cell disorders and is manifested clinically by recurrent infection, most commonly chronic upper and lower respiratory tract disease. Immunoglobulin replacement therapy is available, with at least four different routes of administration. There are as yet no convincing data that allow comparison of the cost-effectiveness of these methods. However, by individualizing therapy for each patient, it is possible to prevent life threatening acute infections, reduce the severity of chronic upper and lower respiratory tract disease, improve pulmonary function and achieve normal levels of IgG. These are the currently acceptable goals of therapy in patients with hypogammaglobulinemia. PMID- 3327583 TI - [In the steps of Jan Evangelista Purkinje in Wroclaw]. PMID- 3327584 TI - ["Roentgen" and Jan Evangelista Purkinje]. PMID- 3327585 TI - [Determination of T-lymphocyte subpopulations using monoclonal antibodies bound to colloidal gold. Correlation with the double immunofluorescence technic]. PMID- 3327587 TI - [The research work of Jan Evangelista Purkinje in cardiology]. PMID- 3327586 TI - [Medical experiments on humans and Purkinje's observations on his own body]. PMID- 3327588 TI - [Bacterial infection complications in the early period after kidney transplantation: azathioprine vs cyclosporin A]. PMID- 3327589 TI - [History of Purkinje's fibers of the heart]. PMID- 3327590 TI - [100 years of electrocardiography]. PMID- 3327591 TI - [Comparative study of the efficacy of hepatitis B virus (HBV) vaccine combined with hepatitis B immunoglobulin(HBIG) versus vaccine alone in the interruption of the perinatal transmission of HBV carrier state]. PMID- 3327592 TI - [Comparison of the different micro-blood sampling methods in the indirect fluorescent antibody test (IFAT) of malaria]. PMID- 3327593 TI - [Recent progress in research on toxoplasmosis in China]. PMID- 3327594 TI - Yawning: neurochemistry, physiology and pathology. PMID- 3327596 TI - When pain afferent neurons fire automatically. PMID- 3327595 TI - Anatomical and biochemical strategy of pain suppressing systems. PMID- 3327597 TI - Treatment of headache among children by progressive relaxation. PMID- 3327599 TI - [Thoughts on Purkinje's concept of the role of science and the scientist in society's development]. PMID- 3327598 TI - Physiology and pharmacology of nociceptive rhythms. PMID- 3327600 TI - [The relation of Jan Evangelista Purkinje to Czech pharmacy]. PMID- 3327601 TI - [Purkinje's journal "Ziva" and pharmacists]. PMID- 3327602 TI - Yeast adenylate cyclase catalytic domain is carboxy terminal. AB - Subcloning of DNA fragments from the gene coding for yeast adenylate cyclase has permitted, after complementation studies in S. cerevisiae cdc35 mutants as well as E. coli cya mutants, to identify the sequence coding for the catalytic domain of the protein. No homology is found between the yeast cyclase catalytic domain and the homologous domain found in E. coli adenylate cyclase. Analysis by Northern blotting of yeast polyA mRNA has shown the existence of multiple transcriptional products of the gene. A putative origin of a major transcript (3.5 kb) would allow synthesis of a ca. 100,000 dalton protein exhibiting cyclase activity in its carboxy terminal domain, and having 7 repeats of 17 amino acids at its amino terminal end. Several note-worthy features, including the possibility of transcriptional control by the general control of amino acids biosynthesis, are present at this putative origin. Data are presented suggesting that a much longer gene product might also be synthesized from the CDC35 gene. Neither the gene organization nor the amino acid sequence of the protein does display any homology with the adenylate cyclase gene and protein of Escherichia coli. This suggests a case of evolutionary convergence for the synthesis of cAMP in prokaryotes and eukaryotes. PMID- 3327603 TI - Genetic characterization of an alpha-specific gene responsible for sexual agglutinability in Saccharomyces cerevisiae: mapping and gene dose effect. AB - A recessive ag alpha 1 mutation leads to specific defect in sexual agglutinability specifically in alpha cells of the yeast Saccharomyces cerevisiae. The cryptopleurine resistance gene cryR 1, closely linked to the mating type locus, was used to select alpha/alpha strains which emerged from alpha/alpha strains by mitotic nonreciprocal recombination, to genetically analyse ag alpha 1, since ag alpha 1 is expressed only in alpha mating type. The ag alpha 1 gene was found to be linked to the centromere tightly, to met3 at 4.4 cM, and to ilv 3 at 12 cM on chromosome X. Sexual agglutinability of alpha cells was shown to be dependent on the dose of the AG alpha 1 gene, using alpha/alpha isogenic strains carrying AG alpha 1/AG alpha 1, AG alpha 1/ag alpha 1 or ag alpha 1/ag alpha 1. The sst2-1 mutation did not suppress the ag alpha 1 mutation. Based on these results, function of the AG alpha 1 gene is discussed. PMID- 3327604 TI - The REC46 gene of Saccharomyces cerevisiae controls mitotic chromosomal stability, recombination and sporulation: cell-type and life cycle stage-specific expression of the rec46-1 mutation. AB - The recessive hyperrecombination mutation rec46-1, isolated by ultraviolet light mutagenesis of the MAT alpha n+1 chromosome VII disomic strain LBL1 (Esposito et al. 1982), enhances the mitotic rates of spontaneous gene conversion, intergenic recombination and restitution of haploidy (due to chromosomal loss or mitotic nondisjunction) in MAT alpha n+1 chromosome VII disomic strains. The rec46-1 mutation does not prevent HO directed homothallic interconversion of mating types. MATa/MaT alpha rec46-1/rec46-1 diploids exhibit the same degree of hyperrecombinational activity as MAT alpha rec46-1 n+1 chromosome VII disomics with respect to gene conversion and intragenic recombination resulting in prototrophy. When compared to MAT alpha rec46-1 n+1 disomics however, MATa/MAT alpha rec46-1/rec46-1 diploids exhibit a ten fold reduced level of hyperrecombinational activity with respect to intergenic recombination and present no evidence of chromosomal loss or nondisjunction resulting in 2n-1 monosomic segregants. MATa/MAT alpha rec46-1/rec46-1 diploids are sporulation deficient. The results obtained demonstrate that the REC46 gene product modulates mitotic chromosomal stability and recombination and is essential for sporulation (meiosis and ascospore formation). PMID- 3327605 TI - Cloned mitochondrial DNA from the zygomycete Absidia glauca promotes autonomous replication in Saccharomyces cerevisiae. AB - We have cloned fragments from mitochondrial and chromosomal DNA of the zygomycete Absidia glauca in Saccharomyces cerevisiae using the ARS selection vector YIp5. Though it has not been possible to select ARS elements from chromosomal DNA, we succeeded in isolating two clones of mitochondrial origin that support autonomous replication in bakers' yeast. DNA from these plasmids has been shown to hybridize with mitochondrial DNA from both mating types. Generation times of the transformed yeast strain in selective medium are around 20 h. In liquid minimal medium only 6% of the cells contain the plasmid; in complete medium a mitotic stability of 50% has been determined. PMID- 3327607 TI - The RAD50 gene of Saccharomyces cerevisiae is not essential for vegetative growth. AB - The gene RAD50 was located by the ability of subclones to restore the Rad+ phenotype following transformation of a rad50-1 mutant. Disruption of the gene was achieved by directed integration of a plasmid carrying a fragment internal to RAD50. Haploids with the disrupted gene are viable and do not differ in growth rate or plating efficiency from isogenic rad50-1 or Rad+ strains. PMID- 3327606 TI - Aspergillus nidulans 5S rRNA genes and pseudogenes. AB - The sequence of four Aspergillus nidulans 5S rRNA genes and of two pseudogenes has been determined. A conserved sequence about 100 bp upstream of the 5S rRNA coding sequences has been found in three genes and one pseudogene. The two pseudogenes correspond to the 5' half of the 5S rRNA coding sequence and their 3' flanking sequences which are not homologous to 5S rRNA are strongly conserved. PMID- 3327608 TI - A new negative control gene for amino acid biosynthesis in Saccharomyces cerevisiae. AB - Enzyme levels in multiple amino acid biosynthetic pathways in yeast are coregulated. This control is effected largely at the transcriptional level by a number of regulatory genes. We report the isolation and characterization of a new negative regulatory gene, GCD4, for this general control system. GCD4 mutations are recessive and define a single Medelian gene on chromosome III. A gcd4 mutation results in resistance to different amino acid analogs and elevated, but fully inducible, mRNA levels of genes under general control. Epistasis analysis indicates that GCD4 acts more directly than the positive regulators GCN1, GCN2, GCN3 and GCN5, but less directly than GCN4, on the transcription of the amino acid biosynthetic genes. These data imply that GCD4 is a negative regulator of the positive effector, GCN4. Although GCD4 occupies the same position relative to the GCN genes as other GCD genes, it produces a unique phenotype. These results illustrate the diversity of function of negative regulators in general control. PMID- 3327609 TI - Immunological homologies between ribosomal proteins amongst lower eukaryotes. AB - Polyclonal antibodies were raised against the purified ribosomal proteins L1 and L2, the 5S rRNA binding protein L3, all from Saccharomyces cerevisiae, and against L1 and L2 from Schizosaccharomyces pombe (numbering according to Otaka and Osawa 1981; Otaka et al. 1983, respectively). For clarity prefixes Sc and Sp have been added to the numbering of proteins derived from S. cerevisiae and S. pombe, respectively. Ribosomal proteins from these yeasts and from Kluyveromyces marxianus, Rhodotorula glutinis, the slime mold Dictyostelium discoideum and the protozoan Tetrahymena thermophila were checked for antigenic cross-reactivity by the immunoblot technique. Anti-ScL1 bound to the largest ribosomal proteins of all organisms but not with equal strength. A fast migrating protein band from R. glutinis was also reactive. Anti-ScL2 reacted strongly with L2 or analogous proteins derived exclusively from the yeasts. Anti-ScL3 cross-reacted only with one protein band from K. marxianus, whereas anti-SpL1 cross-reacted with L1 or its analogues from the other organisms, but also with proteins of lower molecular weight. In S. cerevisiae, these proteins are located exclusively on the small ribosomal subunit. L2 or analogous ribosomal proteins of all organisms were recognized by anti-SpL2 but additionally the ribosomal protein YL28 of S. cerevisiae and fast migrating proteins of T. thermophila exhibited anti-SpL2 binding. PMID- 3327610 TI - A direct study of the relative synthesis of petite and grande mitochondrial DNA in zygotes from crosses involving suppressive petite mutants of Saccharomyces cerevisiae. AB - Work in recent years has produced indirect evidence to support the view that the phenomenon of suppressiveness in yeast is the result of the ability of the petite mtDNA to out-replicate the wild-type genome. We have developed a method, based on fluorography of gels containing restriction fragments of radioactively labelled zygotic mtDNA, by which it has been possible to follow directly the incorporation of label into the two mtDNA species and hence their relative synthesis. Four petite isolates of 70%, 43%, 23% and 12% suppressiveness were tested by this method in crosses with a grande strain. Only the mtDNA from the 70% suppressive petite showed a replicative advantage over the grande mtDNA. The mtDNA from the 43% and 23% suppressive actually appeared to undergo, if anything, less replication in the zygote than the grande mtDNA. It is concluded that while some petites may exhibit suppressiveness as a result of enhanced replicative efficiency of their mtDNA, this cannot be the explanation for all suppressive petite strains. PMID- 3327611 TI - Inhibition of DNA replication in Saccharomyces cerevisiae by araCMP. AB - Cytosine arabinoside (araC), a potent inhibitor of DNA replication in mammalian cells, was found to be completely ineffective in Saccharomyces cerevisiae. The 5' monophosphate derivative, araCMP, is toxic and effectively inhibits both nuclear and mitochondrial DNA synthesis in this organism. Although wild-type strains can be inhibited by araCMP, dTMP permeable (tup-) strains were found to be much more sensitive to the analogue. In vivo labelling experiments indicate that araC enters yeast cells; however, it is extensively catabolized by deamination and breakage of the glycosidic bond. In addition, the analogue is not efficiently phosphorylated in S. cerevisiae owing to an apparent lack of deoxynucleoside kinase activity. These results provide further evidence that deoxyribonucleotides can be synthesized only through de novo pathways in this organism. Finally, araCMP was found to be recombinagenic in S. cerevisiae which suggests, together with other previous studies, that, in general, inhibition of DNA synthesis in yeast promotes mitotic recombination events. PMID- 3327612 TI - Yeast arginine permease: nucleotide sequence of the CAN1 gene. AB - The yeast CAN1 gene, thought to encode arginine permease, has found use in genetics as a selectable locus. We have sequenced the cloned CAN1 gene, which contains an open reading frame of 1770 nucleotides, encoding a polypeptide of calculated molecular weight 65,766. Disruption of this open reading frame largely abolishes CAN1 gene expression, while subcloned fragments of the open reading frame hybridize strand-specifically to a 2.3 kb yeast RNA message. The encoded protein has no leader signal sequence, and is highly hydrophobic, with a possible twelve membrane-spanning domains, several of which have the high hydrophobic moments seen in channel-forming or permease proteins. This protein structure is consistent with the CAN1 product being the plasma membrane arginine permease. PMID- 3327613 TI - Genetic and molecular characterization of argB+ transformants of Aspergillus nidulans. AB - Thirty-three argB- to argB+ transformants of Aspergillus nidulans have been subjected to genetic and molecular analysis. Two showed high levels of mitotic instability although it is suggested that this is a consequence of heterokaryosis rather than instability of the transformation event. Most transformants resulted from the integration of the transforming DNA in tandem with the chromosomal argB locus. The maximum number of inserted sequences was two, to generate three copies of the argB locus. The other main transformant type showed replacement of the argB- mutation by the wild-type allele present on the transforming plasmid. Transformants were also recovered in which the transforming DNA had integrated into non-homologous chromosomal regions. Selfed or hybrid cleistothetica from all transformants, except the gene replacement types gave arginine requiring recombinants. Most transformants showed low levels of meiotic instability. Others displayed varying levels which in some cases differed between selfed and hybrid cleistotheticia. There was some correlation between meiotic instability and the nature of the transformation event. Diploid parasexual and aneuploid analysis located the integrated DNA in each transformant to chromosome III. Two transformants were isolated as heterozygous diploids. A third diploid was isolated as a stable mitotic segregant from one of the mitotically unstable transformants. PMID- 3327615 TI - Defective karyogamy in meiotic segregants of a Candida utilis-Saccharomyces cerevisiae hybrid. AB - Meiotic segregants derived from a Candida utilis--Saccharomyces cerevisiae hybrid obtained by protoplast fusion were crossed to several standard S. cerevisiae laboratory strains. Random spore and tetrad analysis suggested that in these segregants, karyogamy is impaired and internuclear chromosome transfer occurs. PMID- 3327614 TI - Mitotic recombination in stable and unstable chromosome III disomics of Aspergillus nidulans. AB - Approximately 2% of the haploid breakdown sectors of heterozygous chromosome III disomics of Aspergillus nidulans are the result of recombination between the homologous chromosomes. The exchanges are concentrated between the two mutations spanning the centromere. Comparisons are made between disomics hemizygous for the sodIII A1 mutation (Upshall et al. 1979) which are stable when grown at 37 degrees C, and disomics carrying the wild type allele of the sodIII A1 locus, which are unstable under all conditions. It is shown that neither temperature nor the sodIII A1 mutation affect the frequency or pattern of recombination between the homologues. PMID- 3327616 TI - [Dates in the life of Jan Evangelista Purkinje]. PMID- 3327617 TI - [Jan Evangelista Purkinje and his studies on vertigo]. PMID- 3327619 TI - [Sexual aggression. A review of present views]. PMID- 3327620 TI - [Jan Evangelista Purkinje and mental hygiene]. PMID- 3327621 TI - [The theoretical orientation of Prof. A. Heveroch in psychiatry]. PMID- 3327618 TI - [Jan Evangelista Purkinje (1787-1869)]. PMID- 3327623 TI - [Academician Derer (on his unattained 90th birthday)]. PMID- 3327622 TI - [The 70th anniversary of the Great October Socialist Revolution]. PMID- 3327624 TI - Studies on structure-activity relationships of prostacyclin analogs based on molecular mechanics and molecular orbital methods. PMID- 3327626 TI - An investigation into the efficacy of imagery compared with biofeedback in the management of stress in nurses. PMID- 3327625 TI - [Uses of mechanical ventilation after open heart surgery]. PMID- 3327627 TI - Histological localization of 4-S-cysteinylphenol in melanoma-bearing mice. AB - 4-S-cysteinylphenol (4-S-CP), the S-homologue of tyrosine, has been recently synthesized as a selective chemotherapeutic agent against malignant melanoma and has been shown to be a specific substrate for tyrosinase in vitro. In vivo incorporation of 4-S-CP into the B16 and Harding Passey (HP) melanomas and the systemic organs have been evaluated by the autoradiographic method. The distribution of the silver grains indicated that 4-S-CP was selectively incorporated into both the B16 and HP melanomas. 4-S-CP was excreted mainly from the kidneys and there was an accumulation of 4-S-CP in the reticulo-endothelial system. These results seemed to contribute to the utilization of 4-S-CP and other related compounds as chemotherapeutic agents against malignant melanoma. PMID- 3327629 TI - Assessment of the risks associated with the use of chemical carcinogens in biomedical research. AB - Estimates of occupational exposure to chemical carcinogens in biomedical research based on environmental monitoring data, efficiency of containment devices, and accident data suggest that workers may be exposed to a few tenths of a microgram of these carcinogens per work day. Environmental exposure to carcinogenic polycyclic aromatic hydrocarbons and N-nitroso compounds exceeds one microgram per day. Because occupational exposure to chemical carcinogens in the laboratory can be readily controlled and because environmental exposure appears to be greater than the occupational exposure that does occur, the relative risk of occupational exposure does not seem to constitute a major health problem. PMID- 3327631 TI - Positron emission tomography and in vivo measurements of tumour perfusion and oxygen utilisation. AB - The advent of positron emission tomography has provided the clinical investigator with a tool for performing noninvasive (patho)-physiological measurements in humans. The method has been used extensively in the study of cerebral and cardiovascular disease. Oncological applications have been described by a more limited number of centres and have mainly concentrated on cerebral tumours. The first part of this review discusses principles of positron emission tomography and requirements for performing quantitative studies. The second part describes results of one of the most important quantitative techniques: the measurement of tumour blood flow and oxygen metabolism. PMID- 3327630 TI - Can cancer chemotherapy enhance the malignant behaviour of tumours? AB - Cancer chemotherapy is currently undergoing an intensive reappraisal because of its unimpressive performance against the major common cancers. There are a number of possible reasons for this lack of success; one considered here is that under some circumstances anti-neoplastic drug treatment actually increases the malignant behaviour of tumours. Support for this idea comes mainly from experimental studies in which drug treatments increased metastatic spread. Investigation of this phenomenon shows that drug induced modifications of the host, including immunosuppression and vascular damage, can indeed facilitate metastasis. In addition, new data are presented demonstrating that the direct action of drugs on the tumour cells themselves can have similar enhancing effects. The possible mechanisms underlying such direct effects are discussed and the ability of anti-cancer drugs to cause genetic mutations, amplify genes, and alter gene expression are considered. While the nature and extent of this facilitation of tumour malignancy is not fully understood, it is suggested that this possibility should be considered in the design of treatment protocols. PMID- 3327628 TI - Membrane transport and the antineoplastic action of nucleoside analogues. AB - This article summarizes recent studies characterizing nucleoside transport in mammalian cells and discusses evidence for a role of membrane transport in the pharmacologic action of nucleoside analogues. Some of these studies have also addressed the controversy concerning the multiplicity in transport routes. It seems clear that erythrocytes and, perhaps, some other mammalian cells possess a single, broadly specific system for transporting nucleosides. However, substantial evidence from valid studies discriminating between transport and intracellular metabolism suggests that at least some mammalian cells, including some tumor cells, possess more than a single system. Evidence now exists for a determining role of membrane transport of nucleoside analogues in their cytotoxicity and, in the case of one pyrimidine nucleoside (AraC), in therapeutic responsiveness in leukemic patients. There are also numerous examples of transport-related resistance to nucleoside analogues. Included in this article are the results of studies from the authors' laboratory pertaining to the therapeutic activity of the purine nucleoside, FAraA, in murine tumor models. These studies provide evidence for a determining role of both membrane transport and intracellular phosphorylation in the selective antitumor action of this agent against murine leukemia. Substantially increased transport inward of FAraA occurs at pharmacologically achievable concentrations of this agent in tumor cells as compared to drug-limiting, normal proliferative epithelium of the small intestine. The basis for this differential appears to be the kinetic duality of FAraA and adenosine transport inward found in tumor cells, but not in proliferative intestinal epithelial cells. Tumor cells have highly saturable (low influx Km) and poorly saturable (high influx Km) systems for adenosine transport, both of which are shared by FAraA. In contrast, proliferative epithelial cells have only a poorly saturable system for these substrates. If a similar kinetic duality of nucleoside transport is found in other tumor cells certain implications arise concerning the significance of the duality to neoplastic transformation. PMID- 3327632 TI - The structural relationship of blood group-related oligosaccharides in human carcinoma to biological function: a perspective. AB - Blood group-related oligosaccharides have been isolated from a limited number of carcinomas. The carcinoma-associated oligosaccharides show chain elongation, for example due to repeating Gal 1,4 GlcNAc 1,3 sequences, or a higher degree of branching, which permit increased sialylation and fucosylation. Abnormal carbohydrate structures have been demonstrated on tumor cell membranes by immunological techniques, which suggests deletion of ABH, accumulation of 'crypt' antigens such as I and T antigens, and abnormal expression of Lewis antigens. Changes in carcinoma-associated oligosaccharides can result from altered biosynthetic processing in the Golgi apparatus or the occurrence of abnormal tumor glycosyltransferase isoenzymes. Structural alterations of oligosaccharides on the tumor cell membrane are related to the regulation of tumor growth, cell cell interaction, cell differentiation, and metastasis. Glycoproteins secreted by tumor cells into the circulation evoke cellular and humoral immunity and cause immune suppression by binding to cytotoxic T lymphocytes and lymphocyte subsets. The relationship of oligosaccharide structures to biologic function awaits elucidation. PMID- 3327636 TI - Experimental strategies for modification of histocompatibility antigens in tumor cells. AB - Cancer may be thought of as an immunological disorder that arises because certain 'transformed' cells, endowed with the propensity to divide, have learned to evade detection by the immune system. The prospect of intervention by 'immunotherapy' depends very much on our ability to either [1] render cancer cells more recognizable to the immune system, or [2] potentiate the immune system towards a more effective recognition of cancer cells. There is now direct evidence that suppression of the major histocompatibility complex class I antigens, a family of cell-surface glycoproteins required for the presentation of cancer cells to the immune system, is directly responsible for the ability of tumor cells to escape immune surveillance. It has been shown that cancer cells can be made immunogenic either by the expression of an exogenous class I gene introduced by DNA-mediated gene transfer, or by the derepression of endogenous class I genes with interferon; these cells are efficiently rejected by the immune system. Even more interesting is the finding that the immune system can be potentiated to reject tumors by immunization with homologous tumor cells that have been manipulated to express normal levels of class I antigens. Since increasing numbers of human tumors have been found to have greatly reduced levels of class I antigens, these findings suggest a direct route to immunotherapy that involves debulking of the tumor mass, raising the level of class I antigens in a small number of explanted tumor cells, and re-immunizing the host. PMID- 3327637 TI - Systemic antibiotic prophylaxis and reconstructive ear surgery. AB - This paper reports a multicentre, controlled, blind, prospective, randomized study into the use of prophylactic systemic antibiotics in myringoplasty surgery. Seventy-one individuals were clinically and bacteriologically assessed both preoperatively, and for a period of 8 weeks postoperatively. The results showed that antibiotic prophylaxis did not eradicate bacterial pathogens already present in preoperative ears, nor did it prevent their development during the postoperative period. The observation that an ear was wet or dry gave no indication of the actual presence or absence of pathogenic organisms. PMID- 3327635 TI - Combination therapy in stage C and D prostatic cancer: rationale and five year clinical experience. AB - In 1941, Huggins and his colleagues discovered that testicular androgens exert a stimulatory effect on prostate cancer growth. Our group has made the key observations that the human adrenals, in addition to the tests, also secrete important amounts of androgens and cancer cells exhibit a marked heterogeneity of androgen sensitivity. In fact, human adrenals secrete large amounts of precursor steroids that are converted into active androgens in peripheral tissues (including the prostate), thus providing 40% to 50% of total androgens in adult men. The action of these androgens remaining after castration can be inhibited in prostatic cancer tissue by administering a pure antiandrogen that also decreases the local concentration of dihydrotestosterone (DHT). The castration levels of serum testosterone left in men after castration have an important stimulatory activity on the growth of androgen-sensitive normal as well as cancer tissues. Cancer cells have markedly different requirements for androgens. Some cell clones can grow in the presence of minimal amounts of androgens, requiring more complete androgen blockade and more potent antiandrogens for inhibiting growth. Among the compounds recommended as antiandrogens, the most unexpected finding is that many of them are devoid of any antiandrogenic activity. In fact, medroxyprogesterone acetate, chlormadinone acetate, and megestrol acetate have androgenic activity, but do not inhibit the peripheral action of DHT in prostatic tissue. These compounds should not be classified as antiandrogens. Cyproterone acetate, on the other hand, is a mixed agonist-antagonist. The only compounds showing pure antiandrogenic activity are Flutamide and its analogues. There is thus a need for a more complete blockade of androgens of both testicular and adrenal origins in order to exert a maximal inhibitory effect on cancer growth. We have therefore performed clinical studies in previously untreated stage D2 and C prostate cancer patients with the combination therapy using the LHRH agonist [D-Trp6, des Gly NH2(10)] LHRH ethylamide and the antiandrogen Flutamide. There was a significant increase in patients with a complete response, as compared with studies limited to the removal or blockade of testicular androgens. There was also a significant decrease in the number of non-responders, an increased duration of positive response, and a decrease in the death rate. This was achieved with minimal or no side effects, thus preserving a good quality of life. PMID- 3327634 TI - The application of lectins to the characterization and isolation of mammalian cell populations. AB - Mammalian cells invariably contain a vast array of glycosylated moieties, both inside the cell and on the cell surface. There is an increasing awareness of the utility of these carbohydrates in delineating the phenotype or function of many populations of cells. To this end lectins are extremely useful reagents. Lectins are carbohydrate-binding proteins and glycoproteins of non-immune origin derived from numerous plants and animals. A wide variety of lectins with many distinct carbohydrate specificities have been isolated. Historically the most common laboratory techniques utilizing lectins have been agglutination, mitogen stimulation, and fluorescence techniques. Recent advances in the development and conjugation procedure for labels and matrices have led to the creation of numerous novel lectin-based assays. Lectins are currently used not only to identify cells with specified carbohydrate groups, but also to quantitate the carbohydrate groups or to isolate the carbohydrate-bearing cells or structures. PMID- 3327638 TI - Haemodynamic and renal effects of a novel prostaglandin analogue (L644,122(+isomer)) in sheep. AB - 1. Merino-cross ewes were given an intravenous injection of a prostaglandin analogue, (+)-4-(3-[3-[2-(1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]- propyl) benzoic acid, at doses of 0.01, 0.05 and 0.10 mg/kg, on separate days, to determine renal and haemodynamic responses. 2. Peripheral vasodilatory effects, indicated by increases in heart rate and cardiac output, and falls in total peripheral resistance, peaked at 20 min at the two highest doses. By 60 min most values had returned to pre-injection levels. There were no changes in mean arterial pressure. 3. At the highest dose of 0.10 mg/kg there was a fall in glomerular filtration rate, renal blood flow and effective renal plasma flow within 20 min. Urinary sodium and potassium excretion also fell with all three doses tested. 4. Plasma renin concentration increased at the 0.05 and 0.10 mg/kg doses and was still elevated at 60 min. 5. The results of this study in the sheep contrast with others in the dog, where renal blood flow is increased and the rat, where blood pressure is increased, and indicate a species specificity in regard to the analogue's actions. PMID- 3327639 TI - Long-term prognosis of diffuse lupus nephritis. AB - The follow-up of 43 patients with diffuse proliferative lupus nephritis is reported. After histological diagnosis, all patients were treated with 3 intravenous high-dose methylprednisolone pulses and then with low-dose oral steroids and 31 with cytotoxic drugs. Renal and extra-renal exacerbations were also treated with intravenous high-dose steroids. Patients were followed for 1 to 13 years. At 10 years the patient survival rate was 87% and the kidney survival rate was 79%. If 3 extra-renal deaths are excluded, the actuarial 10-year kidney survival rate is 91%. At present, 21 patients do not show any renal abnormalities, 13 patients have normal plasma creatinine but proteinuria, 3 patients have stable renal function impairment, 2 patients have worsening of their renal function, 1 is on regular dialysis. The other 3 patients died (from cardiac failure, cerebral hemorrhage and a car accident). The incidence of flare ups was low (0.1 episodes per year). Severe side effects were rare in this series. It is concluded that the long-term prognosis of diffuse lupus nephritis is becoming considerably better. Therapy based on a short course of intravenous high-dose methylprednisolone and on a maintenance regimen with low doses of steroid and cytotoxic agents can contribute to preserving renal function while avoiding severe side effects. PMID- 3327633 TI - Transport of molecules across tumor vasculature. AB - The vascular-extravascular exchange of fluid and solute molecules in a tissue is determined by three transport parameters (vascular permeability, P, hydraulic conductivity, Lp, and reflection coefficient, sigma); the surface area for exchange, A; and the transluminal concentration and pressure gradients. The transport parameters and the exchange area for a given molecule are governed by the structure of the vessel wall. In general, tumor vessels have wide interendothelial junctions; large number of fenestrae and transendothelial channels formed by vesicles; and discontinuous or absent basement membrane. While these factors favor movement of molecules across tumor vessels, high interstitial pressure and low microvascular pressure may retard extravasation of molecules and cells, especially in large tumors. These characteristics of the transvascular transport have significant implications in tumor growth, metastasis, detection and treatment. PMID- 3327640 TI - ABO blood group incompatible kidney transplantation: a case report and review of the literature. AB - A patient with end-stage renal failure, two previously failed kidney transplants and high serum lymphocytotoxic antibody levels was transplanted electively with an ABO-mismatched, HLA-identical kidney from his sibling. Immunosuppression consisted of pretransplant splenectomy and plasma exchange, followed by rabbit antithymocyte serum, azathioprine, prednisone and plasma exchange in the early post-transplant period. He is now 3 years post-transplant with normal renal function on conventional immunosuppressive therapy. This case, and a review of the literature, suggest that ABO blood group incompatibility need not be an absolute barrier to successful kidney transplantation. ABO incompatible kidney transplantation may be a potentially fruitful area for further research as the demand for donor organs continues to outstrip the supply. PMID- 3327641 TI - Aspects of C1-inhibitor biochemistry and pathophysiology. AB - During the last few years, the structure and function of human C1-inhibitor have been elucidated. Chromogenic substrate assays for determination of C1-inhibitor activity in plasma are available, and have proved to be of value not only for the diagnosis of hereditary angioedema but also in acquired diseases involving C1 inhibitor, such as cold urticaria and autoimmune disorders as well as acute-phase types of disease states. PMID- 3327642 TI - Chlamydia trachomatis serology in ankylosing spondylitis. AB - Demonstration of chlamydial antibodies in patients with ankylosing spondylitis (AS) could show an etiological role of Chlamydia trachomatis in this condition. We studied serum specimens from 50 HLA-B27 positive patients with AS (Group I), 34 HLA-B27 positive patients with other rheumatic diseases (Group II), 67 HLA-B27 positive healthy blood donors (Group III) and 37 healthy untyped blood donors. (Group IV). Measured by an immunoperoxidase assay (IPA) chlamydial IgA (titre greater than or equal to 1:20) was more prevalent in the HLA-B27 positive persons than in the healthy controls not selected for HLA-group (Groups I + II + III vs IV : p less than 0.02). Chlamydia trachomatis IgA-IPA containing sera also had specific IgG-IPA antibodies (greater than or equal to 1:80) in 29 (96%) out of 30 sera from HLA-B27 positive individuals and controls. Conversely, 45% of specific IgG-positive (greater than or equal to 1:80) AS sera, 27.7% sera in Group II, 39.4% Group III sera vs. 11.1% of sera in Group IV had concomitant chlamydial IgA (greater than or equal to 1:20). The differences in the prevalence of specific IgA were statistically significant: Group I vs. IV : p less than 0.01; Group III vs. IV :p less than 0.05 and Gr. I + II + III vs. IV: p less than 0.05. Our data suggest an enhanced antibody production against Chlamydia trachomatis among the HLA-B27 positive individuals whether they have AS or are healthy. PMID- 3327644 TI - Frostbite arthritis consequence of first papal visit to Scotland? PMID- 3327643 TI - A legacy for rheumatology from Sir William Osler. AB - "Of the altruistic instincts, veneration is not the most developed at the present day; but I hold strongly with the statement that it is a sign of a dry age when the great men of the past are held in light esteem". PMID- 3327645 TI - Polychondritis and rheumatoid arthritis. Case report and review of the literature. AB - We present the case history of a 50-year-old man with seropositive erosive rheumatoid arthritis of 30-years standing who developed polychondritis simultaneously with several extra-articular rheumatoid manifestations, such as anaemia, subcutaneous nodules, pericarditis and episcleritis. The relevant literature is reviewed. Gradually, all symptoms and signs disappeared after start of treatment with 30 mg prednisone and 100 mg azathioprine daily. We suggest that the polychondritis in this patient was also an extra-articular manifestation of rheumatoid arthritis. PMID- 3327646 TI - Is the RDW-MCV classification of anaemia useful? PMID- 3327647 TI - Enzyme enhancement for the measurement of protein C. AB - Protein C measurement is now a necessary work-up of a patient with thrombosis. We described an enzyme enhancement of Laurell's immunoelectrophoresis for assay of protein C antigen. With this modification, the rockets are well defined and easily visualized and the sensitivity of the assay increased (2.5%). Samples with low protein C antigen are easily assayed. PMID- 3327649 TI - Effects of hemodialysis on platelets. PMID- 3327648 TI - Oral micronized progesterone. Bioavailability pharmacokinetics, pharmacological and therapeutic implications--a review. AB - Progesterone (P), the natural hormone, binds to its specific receptors to induce specific progestational effects. In addition to this binding, P is able to interfere with the binding sites of other steroids. Therefore the natural hormone exhibits an anti-estrogenic activity, and anti-androgenic activity and also exerts anti-mineralocorticoid effects. For a long time progesterone could not be used in clinical applications because of a rapid liver inactivation after oral administration. An oral micronized preparation of progesterone is now available which produces adequate plasma and tissue levels of progesterone. The preparation reproduces the anti-estrogenic effect of the natural hormone on the endometrium at the dose of 200 mg daily. It also reproduces the anti-mineralocorticoid effect and has no androgenic action. No side effects have been reported as far as lipids profile, coagulation factors and blood pressure are concerned. Therefore oral micronized progesterone appears suitable for hormonal replacement therapy in various areas, essentially postmenopause therapy, premenstrual syndrome, correction of irregular cycles and pregnancy maintenance. PMID- 3327650 TI - The properties of human C5a anaphylatoxin. The significance of C5a formation during hemodialysis. AB - Human C5a anaphylatoxin is a potent bioactive molecule that possesses both spasmogenic and leukocyte-related properties. As such, it normally serves as a local mediator of the acute inflammatory response. Additionally, C5a, through its actions of mononuclear phagocytes, may act to bridge the gap in the acute-chronic inflammatory continuum. While these properties are critical to normal host defense mechanisms, it is now apparent that this anaphylatoxin and/or its des Arg74 derivative, may exert significant systemic effects that are manifest as cardiopulmonary abnormalities and intravascular activation of granulocytes. Knowledge of these properties is critically important for understanding the clinical sequelae exhibited by patients undergoing extracorporeal circulation since we now know that both hemodialysis and cardiopulmonary bypass [28-30] procedures promote intravascular complement activation and C5a formation. Viewed in this context, it seems reasonable to postulate that many of the immediate and delayed responses to extracorporeal circulation might be mediated by C5a formed in the extracorporeal circuit (table IV). For example, it is now recognized that a few particularly susceptible patients display adverse reactions during the initial phases of hemodialysis. The symptoms of this so-called 'first-use syndrome' may range from severe urticaria and angioedema to life-threatening bronchospasm, hypotension, and cardiopulmonary collapse. Some investigators have presented data which suggest that complement-derived products may be causative of these symptoms in some patients [31]. While this hypothesis remains to be confirmed, present evidence clearly demonstrates that C5a alone may produce many of the observed phenomena. In addition to the acute effects produced by C5a, both our own basic studies and the clinical investigations presented by others at this conference suggest that the long-term effects of repeated C5a exposure in the dialyzed patient may be considerable. Thus, there has been a great deal of interest in the role of complement-derived mediators as initiators of leukocyte degranulation and toxic oxygen radical production and an exploration of the significance of these events in the eventual development of chronic pulmonary fibrosis in the dialyzed patient. Similarly, the effects of repeated exposure to IL-1 that has been postulated to occur as a result of C5a triggering of monocytes during dialysis is currently an active area of investigation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327651 TI - Beta-2-microglobulin-related amyloidosis in long-term hemodialysis patients: possible pathogenetic mechanisms. PMID- 3327652 TI - Stochastic curtailing for comparison of slopes in longitudinal studies. AB - In some clinical trials, rate of change of a physiological function is used as a surrogate for a more serious outcome. We assume an expected change linear in time for each study participant with variation in slopes and intercepts from individual to individual and repeated measures over time for each individual. We also assume that deviations of response for an individual from expected response have zero mean, constant variance, and are uncorrelated. Under these assumptions we describe ways in which stochastic curtailing as defined by Lan, Simon, and Halperin (Commun Stat Seq Anal 1:207-219, 1982) can be implemented in a two treatment trial for one-sided comparison of slopes in the two groups. Staggered entry is taken into account, as is the possibility that some of an individual's responses are not available; this is assumed to be random. The analysis assumes the number of participants in each group is large and that most individuals have at least two measurements (including baseline value). The possibility that rate of change is not constant and its consequences are discussed. PMID- 3327653 TI - Issues in designing sequential stopping rules for monitoring side effects in clinical trials. AB - In a clinical trial of a new treatment, severe side effects may be a problem, and the trial may have to be stopped if the incidence is too high. We need to anticipate the need for such a decision to halt the trial early, and possibly design formal stopping rules for an excess of untoward events. The work presented here discusses the issues involved in such monitoring in comparison with more conventional analysis of the outcome variable. Stopping rules are derived by application of the sequential probability ratio test (SPRT), followed by computation of the exact size and power and adjustments of the consequent rules to achieve chosen operating characteristics appropriate to a monitoring situation. Rules are also derived from a Bayesian approach. These rules are applied to an illustrative trial and compared to the actual conditions that lead to the closing the trial. PMID- 3327654 TI - The Cholesterol Lowering Atherosclerosis Study (CLAS): design, methods, and baseline results. AB - The Cholesterol Lowering Atherosclerosis Study (CLAS) is a prospective, placebo controlled, angiographic trial designed to test the hypothesis that aggressive lowering of LDL cholesterol with concomitant increase in HDL cholesterol will reverse or retard the atherosclerotic process. Specifically, CLAS was designed to determine whether combined therapy with colestipol plus niacin will produce clinically significant change in coronary, carotid, and femoral artery atherosclerosis and coronary bypass graft lesions. To this purpose, 188 subjects were randomized to diet plus drug or diet plus placebo. We report on methodological aspects of planning and evaluating this study, including the choice of the study population, procedures for recruitment, the experimental design including sample size considerations, methods for evaluating outcome, and methods for evaluating compliance to treatment. Comparison of baseline data indicated no significant differences between groups at the time of randomization. Subjects were predominantly male, Caucasian, 54 years of age, 20% above ideal weight, with normal blood pressure. The average age at bypass was 50 years. The average lipids were cholesterol (243 mg/dL), HDL (45 mg/dL), and LDL (168 mg/dL). Finally, the distribution of baseline coronary stenosis was equivalent between the two groups (average number of lesions per subject = 10.6). PMID- 3327655 TI - Grammatical morphology in aphasia: evidence from three languages. AB - Aspects of grammatical morphology in Broca's and Wernicke's aphasia were elicited under controlled conditions in three language groups: English, Italian and German. Results suggest that the agrammatism/paragrammatism distinction does not work well for richly-inflected languages. Language-specific ratios of closed class morphology were preserved even among non-fluent patients, with significantly more morphology produced by German and Italian patients. German and Italian patients were also much more likely to furnish the article before nouns- despite or perhaps because of the fact that articles are more complex and informative in those languages. Although patients assigned the correct article most of the time, there were a significant number of article errors (i.e. paragrammatic substitution). Error analyses showed that substitutions are not random, reflecting difficulty in access rather than loss. Substitutions were more common in German, where the complex case and gender markings on the article increase the probability of error. Within each language, error patterns were quite similar for Broca's and Wernicke's aphasics. However, at a detailed level patient group differences in error production were detected. German Broca's aphasics tend to avoid difficult case forms by substituting a simpler, less marked morphosyntactic frame. Wernicke's aphasics try instead to produce the more marked, oblique constructions, resulting in a less conservative error pattern. PMID- 3327656 TI - Eosinophilic granuloma of the cervical spine without vertebrae plana. AB - A case of eosinophilic granuloma of the cervical spine is described. Cervical radiography and computed tomography demonstrated destruction of pedicles and posterior portions of the neural arch. Vertebral body heights were essentially preserved and the importance of this finding is underscored. Computed tomography played an important role in evaluating the extent of this disease. PMID- 3327657 TI - Magnetic resonance imaging appearance of primary squamous cell carcinoma of the breast. AB - Primary squamous cell carcinoma is a rare form of carcinoma of the breast. This article reports on two such lesions with their appearance in magnetic resonance imaging and reviews the scant English literature of the past 10 years. Most of these tumors are circumscribed and have areas of necrosis. The prognosis in patients with this disease is the same as that of adenocarcinoma of the same size and stage. PMID- 3327658 TI - Aortic valve stenosis: etiology, pathophysiology, evaluation, and management. AB - More patients with valvular aortic stenosis are being recognized, especially elderly patients with degenerative disease of the aortic valve. For nearly all patients with aortic valvular stenosis, 2-D and Doppler echocardiography have been found to be reliable for both the diagnosis and the establishment of severity (by gradient and valve area) of stenosis as well as for assessment of left ventricular function. Therefore, we project a lesser role for cardiac catheterization in the future, limited to definition of the coronary anatomy. Aortic valve replacement remains the proven therapy for patients with symptomatic aortic stenosis, although the decalcification/lithotripsy and balloon valvuloplasty techniques appear to be promising options in selected patients. PMID- 3327659 TI - Radiology of the lymphomas. AB - Lymphomas are a group of diseases that provide the radiologist and clinician with unusual challenges. In most cases, an understanding of the histologic classification and staging is essential to design the imaging workup for the patient. Precise staging is critical, particularly for patients with HD and extranodal NHL. The malignant lymphomas share many similar radiographic features, yet have notable differences. An understanding of the pattern of extension of HD is useful in choosing an imaging modality for both staging and follow-up. Contiguous extension of HD follows lymphatic channels and is primarily limited to nodal compartments in the mediastinum and retroperitoneal lymph nodes. On the other hand, NHL may be either widespread or extranodal and localized. In the first instance, the histology will be low grade; in the second, intermediate or high grade. An understanding of these histologic clues is critical to the structuring of an efficient staging workup for the patient with NHL. Posttreatment follow-up imaging strategies should be governed by the fact that in both HD and NHL, recurrences are usually apparent within two years following initial treatment. Treatment complications must be separated from the manifestations of recurrent disease, a particularly important consideration in following up the patient with HD. PMID- 3327660 TI - The limping child. PMID- 3327662 TI - [Comparison of human monocomponent insulin with beef and pork monocomponent insulin in the treatment of a diabetic with insulin resistance]. PMID- 3327661 TI - [Advances and current status of clinical research on endometriosis]. PMID- 3327663 TI - [Indirect immunoperoxidase assay: a useful diagnostic method for trichinosis]. PMID- 3327664 TI - Gene therapy: efforts at developing large animal models for autologous bone marrow transplant and gene transfer with retroviral vectors. AB - Two new large animal models, non-human primates and fetal sheep, have been developed in an effort to determine the feasibility of using retroviruses for gene therapy. The retroviral vectors N2 and SAX have been used to introduce the genes for neomycin phosphotransferase (neoR, conferring resistance to the antibiotic G418) and human adenosine deaminase (ADA; EC 3.5.4.17), respectively. Varying levels of human ADA activity have been detected in six of the eight SAX treated monkeys analysed. In the monkey with the greatest activity, human ADA levels approximately 0.5% of endogenous monkey ADA levels were detected. By in situ hybridization, roughly one in 100 bone marrow cells were found to express vector DNA. Sheep have been used for studies of the infectability of fetal blood progenitors in vivo. Blood cells were treated with the N2 vector at the 96th day of gestation, and marrow cells were assayed for the presence of G418-resistant haematopoietic progenitors, starting from one week after birth (62 days after treatment). Up to 33% of colony-forming progenitors were drug resistant initially and, although the proportion of resistant colony-forming units declined, a level of 10% has been found 153 days after transplantation. Human bone marrow has also been treated with the N2 vector, resulting in 1-2% G418-resistant progenitors. PMID- 3327666 TI - [Four outbreaks of clonorchiasis sinensis in Suibin Farm, Heilongjiang Province]. PMID- 3327665 TI - Genetic architecture of inter-individual variability in apolipoprotein, lipoprotein and lipid phenotypes. AB - Phenotypes that predict coronary heart disease (CHD) are the consequence of interactions between many genetic and environmental factors. Quantitative measures of plasma apolipoproteins, lipoproteins and lipids are examples of phenotypes that link genetic and environmental factors to the CHD end-point. Population studies in Hawaii, Michigan and elsewhere have established that a significant fraction of variability in these phenotypes is attributable to genetic differences among individuals. Recent advances in molecular biology provide measures of the gene loci that code for the apolipoproteins, the cellular receptors for lipoprotein particles and the catalysts and cofactors in lipoprotein metabolism. By measuring polymorphic protein variability and restriction site variability in small regions of DNA known to contain genes that code for the proteins involved in these functions, it is possible to assign polygenetic effects to specific alleles or haplotypes. This 'measured genotype' approach may be used to study the genetic architecture (number of loci involved, the frequencies and effects of their alleles, and the type of loci, i.e., structural or regulatory) of quantitative variation in the plasma apolipoproteins, lipoproteins and lipids. This paper reviews statistical models, sampling designs and results of studies designed to estimate the genetic architecture of selected apolipoproteins, lipoproteins and lipids. The usefulness of these studies for answering questions about the prediction of CHD in the population, the family and the individual are discussed and the directions that human quantitative genetic studies will take in the future are considered. PMID- 3327667 TI - [Progress in the research on soil sanitary standards in the USSR and my tentative ideas on the research projects in China]. PMID- 3327668 TI - Recent advances in non-steroid anti-inflammatory drugs. AB - Recent advances in NSAID, particularly those developed in Japan, are described. They may be classified into some categories. Firstly, useful new compounds such as propionic acids which have an excellent pharmacological activity with mild side-effects have been developed. Secondly, the progress of drug delivery systems (DDS) has been observed in the treatment with NSAID. Thirdly, a new type of NSAID, whose mechanism of action is different from the inhibition of cyclooxygenase. Lastly, NSAID are widely used against not only inflammatory disease but also the other diseases in which prostaglandins and thrombosis have an important role in pathogenesis. PMID- 3327669 TI - Pirprofen, naproxen and placebo in the treatment of primary dysmenorrhoea. AB - In a double-blind between-patient clinical trial, 82 patients were admitted to the study and after a preliminary period with placebo administered in single blindness, they were divided into two groups: "placebo-responders" and "placebo non-responders". Responders were treated with pirprofen capsules (400 mg, b.i.d.) or placebo capsules b.i.d.; non-responders were treated with pirprofen capsules (400 mg, b.i.d.) or naproxen capsules (250 mg, b.i.d.) according to two different randomisation lists, for four menstrual cycles. A complete medical examination, including evaluation of associated symptomatology, menstrual flow entity and global efficacy, was performed after each cycle. In the responders group results were significantly better with pirprofen than with placebo after only the second cycle of treatment (p less than 0.01). In the non-responders group both treatments showed "good" or "excellent" results in more than 80% of patients in all cycles. In all patients there were no significant differences in the evaluation of the menstrual flow entity, of the associated symptomatology and of the number of side-effects. PMID- 3327670 TI - Monoclonal antibodies against components of the myoplasm of eggs of the ascidian Ciona intestinalis partially block the development of muscle-specific acetylcholinesterase. AB - The myoplasm of Ciona intestinalis eggs, believed to contain cytoplasmic determinants responsible for muscle cell differentiation in ascidian embryos, emits weak pale-blue autonomous fluorescence. Utilizing this feature as a marker, the cytoplasm was isolated according to the method described by Jeffery (1985b). Electron microscopy showed that the isolated cytoplasm contained mitochondria, pigment granules, yolk particles and fine granular materials; these are ultrastructural components of the myoplasm of the intact egg. Monoclonal antibodies were prepared against the isolated cytoplasm. Twelve monoclonal antibodies, identified by indirect immunofluorescence, stained the myoplasmic region. When unfertilized eggs were centrifuged, stratifying their mitochondria and some other cytoplasmic components, components identified by several antibodies, for example IIG6B2, remained at the peripheral cytoplasm of the egg. Other antibodies recognized components stratified as the mitochondrial layer. Four representative antibodies were microinjected into fertilized eggs in order to examine their inhibitory effects on the muscle differentiation; the IIG6B2 antibody blocked the development of muscle-specific acetylcholinesterase in more than 80% of the embryos tested. PMID- 3327671 TI - An ECM substratum allows mouse mesodermal cells isolated from the primitive streak to exhibit motility similar to that inside the embryo and reveals a deficiency in the T/T mutant cells. AB - The mesodermal cell layer is created by ingression and migration of the cells from the primitive streak region in mouse embryos on day 7 of pregnancy. In order to study the mechanisms of mesodermal cell migration during development, the mesodermal cells isolated from the primitive streak were cultured on various substrata, and cell behaviour and motility were analysed with a time-lapse video system. The mesodermal cells on the surface of extracellular matrix (ECM)-coated dishes (ECM produced by bovine corneal endothelial cells) showed extensive migration at a mean rate of approx. 50 micron h-1. They also showed frequent cell division and exhibited contact paralysis of lamellipodia and contact inhibition of movement. On plastic or glass surfaces, however, the mesodermal cells became more flattened and less motile (approx. 20-30 micron h-1). Cell shape and mean rate of movement on the ECM were very similar to those in situ, as investigated in a previous study (Nakatsuji, Snow & Wylie, 1986). Therefore, this culture condition could provide a useful experimental system for analysing the cellular basis of normal and abnormal morphogenetic movements in mouse embryos. Employing such a culture system, we studied motility of the mesodermal cells from embryos homozygous for Brachyury (T) mutation, which are lethal at the midgestation stage in utero. Histological observations have suggested that anomalous morphogenesis of the T/T embryos may be brought about by defects in migration of the mesodermal cells derived from the primitive streak. When mesodermal cells from the primitive streak of the T/T mutant embryos on days 8-9 were cultured on the ECM substratum, mean rate of cell migration was significantly reduced compared to cells from normal embryos. Results support the idea of retarded migration by the mutant mesodermal cells as an important factor causing abnormalities in morphogenesis. PMID- 3327672 TI - Trophectoderm surface expression of the cell adhesion molecule cell-CAM 105 on rat blastocysts. AB - A variety of cellular interactions is involved in the process of implantation of the mammalian embryo into the uterine tissue. Recent discoveries have demonstrated that intercellular recognition and adhesive events are governed by a class of cell surface molecules known as cell adhesion molecules (CAMs). In the present report, we have investigated the occurrence of the well-characterized cell adhesion molecule cell-CAM 105 on the surface of rat pre- and peri implantation embryos of various stages. This was carried out by indirect immunofluorescence microscopy employing affinity-purified rabbit antibodies against cell-CAM 105. The embryonal stages investigated comprised morulae, normal day-4 blastocysts, and delayed and adhesive blastocysts obtained by using the method of experimentally delayed implantation. Cell-CAM 105 was absent in the early-morula stage, but in normal day-4 blastocysts and delayed blastocysts a specific staining for cell-CAM 105 was seen on the entire surface. However, adhesive-stage blastocysts exhibited a marked polarity with staining of the polar trophoblast cells. Scanning electron microscopy of adhesive-stage blastocysts revealed that the stronger staining of the polar region was not due to a greater number of microvilli on the polar trophoblast cells. Thus, it seems as if cell CAM 105 is lost or masked from the surface of the mural trophoblast cells of adhesive-stage rat blastocysts. Since the mural trophoblast cells are the first to adhere to the uterine luminal epithelium during the onset of implantation and subsequently invade the uterine stroma, we suggest that the apparent downregulation of cell-CAM 105 in the mural trophoblast cells might be linked to the acquisition of trophoblast invasiveness. PMID- 3327673 TI - The use of felodipine in the treatment of severe hypertension. AB - To investigate the use of felodipine in severe hypertension 2 separate studies were carried out. In the first study, 101 patients on a fixed combination of atenolol 100mg and chlorthalidone 25mg who required additional or 'third line' therapy for proper control, were randomised to either felodipine or hydralazine and the dosage was increased if the supine diastolic blood pressure was greater than 90mm Hg. Felodipine reduced blood pressure more effectively than hydralazine and the incidence of adverse reactions was similar in both groups. In the second study, 17 patients with severe hypertension (WHO stage III), who had not been controlled by therapy with atenolol, thiazide diuretic and hydralazine, prazosin or nifedipine were studied. Patients were subsequently controlled by a combination of atenolol, frusemide or bumetanide, and minoxidil. Once stabilised, the patients then took part in a double-blind crossover study comparing minoxidil and felodipine. The patients' blood pressure was the same on both treatment regimes but their bodyweight was lower after felodipine administration. Felodipine is probably more effective than hydralazine and as effective as minoxidil in treating severe hypertension. As felodipine is usually well tolerated it should prove a useful drug in treating refractory hypertension. PMID- 3327674 TI - Aspects on the benefit-risk balance of felodipine in hypertension. AB - This review attempts to evaluate the benefit-risk balance of felodipine in the treatment of hypertension. Known positive and negative properties of felodipine are considered. Although accurate benefit-risk statements may be difficult even for old, well-established drugs it is concluded that felodipine appears to be an effective and well tolerated new antihypertensive drug. The reduction in blood pressure during felodipine treatment has been superior to that seen with established antihypertensive drugs in controlled studies. PMID- 3327675 TI - Hypertension in the elderly. Its diagnosis in general practice and treatment with felodipine and metoprolol. PMID- 3327676 TI - Clinical pharmacokinetics of felodipine. A summary. AB - Felodipine is completely absorbed from the gastrointestinal tract. However, the amount reaching the systemic circulation is reduced to about 15% because of first pass degradation. The bioavailability is constant within the dose interval of 5 to 40mg orally. The frequency histogram of the area under the plasma concentration-time curve (AUC) seems to be normally distributed. The disposition of felodipine is independent of the administered dose over the intravenous dose interval (1-3 mg). The plasma concentration-time curve declines in 3 distinct phases. The mean elimination half-life of felodipine is approximately 25h. Felodipine is extensively distributed to extravascular tissues. The volume of distribution of felodipine is about 10 L/kg, implying that less than 1% of the amount of drug in the body is localised in the blood. Felodipine is more than 99% bound to plasma proteins. Mean total clearance from the blood is 1 to 1.5 L/min and, therefore, felodipine is considered a high clearance drug. Felodipine is metabolised completely and no unchanged drug is eliminated in the urine. The first step in the metabolism involves oxidation to the corresponding pyridine derivative by the cytochrome P-450 system. Identified metabolites in plasma and urine are devoid of vasodilating activity. Long term treatment, and the presence of hypertension and impaired renal function do not affect the disposition of felodipine. Elderly people may have higher plasma levels than the young and middle-aged. Impaired liver function significantly decreases systemic clearance. Cimetidine and food affect felodipine kinetics, but with negligible clinical implications. Therapeutic concentrations of felodipine do not interact with highly protein-bound drugs and these drugs have no effect on the binding of felodipine to human plasma proteins in vitro. Plasma levels of digoxin and metoprolol tended to increase during felodipine treatment. There is a significant correlation between plasma concentrations of felodipine and haemodynamic effects in both healthy subjects and hypertensive patients during short term as well as during long term treatment. PMID- 3327677 TI - Felodipine versus Moduretic. A double-blind parallel-group multicentre study. AB - In a double-blind parallel-group study 133 patients with mild to moderate essential hypertension were randomised to felodipine 5mg twice daily or Moduretic mite every morning after a run-in placebo period of 1 to 2 weeks. All previous antihypertensive therapy was withdrawn at the start of the run-in period. After 4 weeks the dose of felodipine was increased to 10mg twice daily, and Moduretic mite was replaced by Moduretic in patients with a diastolic blood pressure of greater than 80mm Hg. On the low dose, the supine blood pressure on felodipine was reduced by 24/14mm Hg from 174/105mm Hg, and on Moduretic mite by 19/11mm Hg from 171/103mm Hg. After the increase in dosage blood pressure was lowered further. There was no statistically significant difference in blood pressure reduction between the 2 groups. Severe adverse drug experiences (ADEs) were few and equally distributed. However, more felodipine patients were withdrawn because of ADEs. Potassium levels decreased and uric acid levels increased significantly in the Moduretic group. PMID- 3327678 TI - Effects of felodipine and metoprolol on blood pressure, plasma renin, angiotensin II, aldosterone and catecholamines in hypertensive patients. AB - Oral administration of felodipine to 10 patients with mild essential hypertension acutely reduced the brachial artery pressure by 15/13mm Hg. The tachycardia which occurred was sustained for 90 minutes together with an elevated plasma noradrenaline concentration. Addition of intravascular metoprolol after 90 minutes decreased heart rate. The felodipine-induced increase of plasma renin activity (100%; p less than 0.001) was completely reversed by metoprolol. Plasma angiotensin II (PA II) rose by 15% (p less than 0.05) during felodipine, whereas plasma aldosterone concentration was not significantly affected. PMID- 3327679 TI - Short and long term treatment of essential hypertension with felodipine as monotherapy. PMID- 3327680 TI - Felodipine monotherapy in systolic hypertension in the elderly. PMID- 3327681 TI - Baroreflex control of renin release in spontaneously hypertensive rats after administration of felodipine. AB - The baroreflex control of heart rate will be rapidly reset to operate at a lower pressure level after blood pressure reduction by felodipine. The present study investigates whether the baroreflex control of renin release in spontaneously hypertensive rats (SHR) will also be reset after prolonged felodipine administration. Conscious SHR, fitted with catheters in the tail artery and vein, were given felodipine intravenously for 5 hours. The initial reflexogenic elevation in plasma renin activity and heart rate caused by felodipine-induced blood pressure reduction were successively normalised with time. Heart rate returned to pre-drug values after 3 hours and plasma renin activity after 5 hours of stable blood pressure reduction. This indicates rapid resetting of baroreflex control of both cardiac and renal function after blood pressure reduction by felodipine. PMID- 3327682 TI - Pharmacodynamic properties of felodipine. AB - This overview presents the pharmacodynamic properties of felodipine as studied in animal experiments with emphasis on results from our laboratory. Felodipine is 100-fold more potent in causing inhibition of spontaneously active vascular smooth muscle than myocardium in vitro. This vascular selectivity is significantly greater than that of nifedipine (potency ratio 15). Verapamil, D 600, La3+ and reduction of [Ca2+]o lack selectivity. The cellular mechanisms underlying this variable selectivity are not clear at present. In conscious spontaneously hypertensive rats (SHR), the plasma concentration required for 20% reduction of mean arterial pressure is approximately 10 nmol. Mean arterial pressure is lowered dose-dependently as a result of reduced peripheral vascular resistance accompanied by increased cardiac output due to transient tachycardia and increased stroke volume. There was rapid resetting of the baroreflex set point but unaltered sensitivity after felodipine and hydralazine in SHR. Therefore, the reflexogenic increase in heart rate and plasma renin activity subsided within 3 to 5 hours of continuous felodipine administration in SHR. In addition, there was a uniform dilatation of the peripheral vascular beds after felodipine administration. During long term treatment of SHR with felodipine, progression of left ventricular and vascular wall hypertrophy was prevented. Within the 'therapeutic dose range', the only primary effect observed in addition to arterial vasodilation is diuresis/natriuresis caused by a renal tubular action. PMID- 3327683 TI - Felodipine in ischaemic heart disease. AB - The effects of felodipine on haemodynamics and exercise capacity have been studied in patients with angina pectoris. In a study of 11 patients undergoing cardiac catheterisation with concomitant beta-blockade, oral felodipine (0.075 mg/kg) increased resting heart rate by 16%. During atrial pacing at 100 beats per minute, felodipine decreased mean systemic arterial pressure by 9.6% and systemic vascular resistance by 30% and increased cardiac index by 30%. There was no significant effect on pulmonary haemodynamics or left ventricular end-diastolic pressure and the isovolumic and ejection phase indices of left ventricular contractility were unchanged. In a randomised double-blind study of 14 patients, felodipine, when added to regular beta-blockade, reduced the frequency of episodes of angina and the amount of glyceryl trinitrate consumed. At a similar plasma concentration to that in the above study, felodipine significantly increased exercise tolerance by 16%, without producing a change in the maximal double product. Resting supine heart rate was increased by 7.3% after felodipine administration; supine systolic and diastolic blood pressures were decreased by 13% and 12%, respectively, and erect systolic and diastolic blood pressures by 14% and 10%, respectively. Only minor adverse effects were reported. Because of its systemic vasodilating properties, felodipine should be a useful adjunct to beta-blockade in patients with angina pectoris. PMID- 3327684 TI - Felodipine in heart failure. A double-blind, randomised, placebo-controlled parallel-group study in 23 patients. PMID- 3327685 TI - Glucose tolerance and secretion and clearance of insulin during long term felodipine treatment. PMID- 3327686 TI - GUS fusions: beta-glucuronidase as a sensitive and versatile gene fusion marker in higher plants. AB - We have used the Escherichia coli beta-glucuronidase gene (GUS) as a gene fusion marker for analysis of gene expression in transformed plants. Higher plants tested lack intrinsic beta-glucuronidase activity, thus enhancing the sensitivity with which measurements can be made. We have constructed gene fusions using the cauliflower mosaic virus (CaMV) 35S promoter or the promoter from a gene encoding the small subunit of ribulose bisphosphate carboxylase (rbcS) to direct the expression of beta-glucuronidase in transformed plants. Expression of GUS can be measured accurately using fluorometric assays of very small amounts of transformed plant tissue. Plants expressing GUS are normal, healthy and fertile. GUS is very stable, and tissue extracts continue to show high levels of GUS activity after prolonged storage. Histochemical analysis has been used to demonstrate the localization of gene activity in cells and tissues of transformed plants. PMID- 3327687 TI - cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, p150,95. AB - The leukocyte adhesion receptors, p150,95, Mac-1 and LFA-1 are integral membrane glycoproteins which contain distinct alpha subunits of 180,000-150,000 Mr associated with identical beta subunits of 95,000 Mr in alpha beta complexes. p150,95 alpha subunit tryptic peptides were used to specify oligonucleotide probes and a cDNA clone of 4.7 kb containing the entire coding sequence was isolated from a size-selected myeloid cell cDNA library. The 4.7-kb cDNA clone encodes a signal sequence, an extracellular domain of 1081 amino acids containing 10 potential glycosylation sites, a transmembrane domain of 26 amino acids, and a C-terminal cytoplasmic tail of 29 residues. The extracellular domain contains three tandem homologous repeats of approximately 60 amino acids with putative divalent cation-binding sites, and four weaker repeats which lack such binding sites. The cDNA clone hybridizes with a mRNA of 4.7 kb which is induced during in vitro differentiation of myeloid cell lines. The p150,95 alpha subunit is homologous to the alpha subunits of receptors which recognize the RGD sequence in extracellular matrix components, as has previously been shown for the beta subunits, supporting the concept that receptors involved in both cell-cell and cell-matrix interactions belong to a single gene superfamily termed the integrins. Distinctive features of the p150,95 alpha subunit include an insertion of 126 residues N-terminal to the putative metal binding region and a deletion of the region in which the matrix receptors are proteolytically cleaved during processing. PMID- 3327688 TI - A naturally occurring gene encoding the major surface antigen precursor p190 of Plasmodium falciparum lacks tripeptide repeats. AB - Plasmodium falciparum merozoites have variable surface proteins that are processed from a 190-kd precursor protein (p190). The gene encoding p190 exists in two allelic forms and cross-over events occurring mainly near the 5' end, combined with isolate-specific tripeptide repeats, contribute to its antigen diversity. We have sequenced a large portion of the p190 gene from the parasite isolate RO-33 (Ghana). Remarkably, the typical N-terminal tripeptide repeat structure is lacking. Apart from mutations in the variable parts, the gene appears identical to the MAD-20 allele (Papua, New Guinea). Southern blot analysis detects p190 genes similar to RO-33 in other parasite isolates independent of their geographical origin. The lack of p190 repeats in RO-33 eliminates the possibility that they are involved in host cell recognition or integration and restricts their function to immune escape. PMID- 3327689 TI - A yeast small nuclear RNA is required for normal processing of pre-ribosomal RNA. AB - In Saccharomyces cerevisiae, seven snRNAs (snR3, 4, 5, 8, 9, 10 and 17) are retained in the nucleus under conditions in which nucleoplasmic RNAs are lost, and may be nucleolar. All of these snRNAs show properties consistent with hydrogen bonding to pre-ribosomal RNAs; snR5 and 8 with 20S pre-rRNA, snR3, 4, 10 and 17 with 35S pre-rRNA and snR9 with 20-35S RNA. Strains lacking snR10 are impaired in growth and specifically defective in the processing of 35S RNA. Processing is slowed, leading to 35S RNA accumulation and most cleavage occurs, not at the normal sites, but at sites which in wild-type strains are used for subsequent steps in rRNA maturation. PMID- 3327692 TI - Restriction of the human kidney band 3-like anion exchanger to specialized subdomains of the basolateral plasma membrane of intercalated cells. AB - In this study, the kidney analog of the erythrocyte anion exchanger, band 3, served as the first example of an anion translocating membrane protein in a nucleated cell type to be localized at the ultrastructural level. Kidney band 3 was found to be confined to the basolateral membrane of the intercalated cells in the human collecting duct. The immunogold label displayed a striking non-uniform distribution along the basolateral plasma membrane with a preferential concentration at pleated areas of the membrane surface. The pleated portions are suggested to represent specialized subdomains to which the band 3 analog might be restricted by linkage via ankyrin to the spectrin-based membrane cytoskeleton. The immunolabel did not extend apically to the level of the zonula adherens and zonula occludens indicating that tight junctions might not be important for maintaining the polarized distribution of this integral membrane protein. Association of antibody label with the rough endoplasmic reticulum and other types of cytoplasmic membranes indicate pathways in the biosynthesis and degradation of this anion exchanger. PMID- 3327690 TI - Preferential recombination between GC clusters in yeast mitochondrial DNA. AB - Yeast mitochondrial DNA molecules have long, AT-rich intergenic spacers punctuated by short GC clusters. GC-rich elements have previously been characterized by others as preferred sites for intramolecular recombination leading to the formation of subgenomic petite molecules. In the present study we show that GC clusters are favored sites for intermolecular recombination between a petite and the wild-type grande genome. The petite studied retains 6.5 kb of mitochondrial DNA reiterated tandemly to form molecules consisting of repeated units. Genetic selection for integration of tandem 6.5 kb repeats of the petite into the grande genome yielded a novel recombination event. One of two crossovers in a double exchange event occurred as expected in the 6.5 kb of matching sequence between the genomes, whereas the second exchange involved a 44 bp GC cluster in the petite and another 44 bp GC cluster in the grande genome 700 bp proximal to the region of homology. Creation of a mitochondrial DNA molecule with a repetitive region led to secondary recombination events that generated a family of molecules with zero to several petite units. The finding that 44 bp GC clusters are preferred as sites for intermolecular exchange adds to the data on petite excision implicating these elements as recombinational hotspots in the yeast mitochondrial genome. PMID- 3327691 TI - Mutants of elongation factor Tu promote ribosomal frameshifting and nonsense readthrough. AB - This is the first report of ribosomal frameshifting promoted by mutants of the elongation factor Tu (EF-Tu). EF-Tu mutants can suppress both -1 and +1 frameshift mutations. The level of nonsense readthrough is also increased at some UGA (this paper) and UAG (Hughes, 1987) sites by these mutants. Suppression occurs when a mutant tuf allele is paired with a wild-type copy of the other tuf gene but is most efficient when both tuf genes are mutant. Frameshifting mediated by the tuf alleles studied, tufA8 and tufB103, is not general; indeed most frameshift mutations are not suppressed. Several possible mechanisms by which mutant EF-Tu may cause frameshifting are discussed. PMID- 3327694 TI - Psychophysiological mechanisms in silent myocardial ischaemia. AB - Six levels of coronary pain are defined and for each of them explanations for absence of pain in asymptomatic myocardial ischaemia are given: Level I: Myocardial ischaemia which can be less pronounced in amount during asymptomatic episodes. Level II: Adequate stimulus (chemical, mechanical) where biosynthesis of algogesic substances, degree of local mechanical involvement and spatial distribution may be different. Level III: For neuronal encoding the intensity theory is mainly for coronary pain, presupposing a central pain threshold which is higher in asymptomatic patients. Level IV: Conduction of painful information may be interrupted by destruction of afferent nerve ways. Level V: Spinal transmission: resting tone and ability to activate neural and humoral (endorphinergic) pain inhibition systems are stronger in asymptomatic patients. Level VI: Central processing: cognitive mechanisms (coping style) affect perception of coronary pain with differences in symptomatic and silent myocardial ischaemia. PMID- 3327693 TI - Streptococcal protein G-gold complex: comparison with staphylococcal protein A gold complex for spot blotting and immunolabeling. AB - Protein G, a cell wall protein isolated from human group G streptococci strain G148, binds in a similar manner as protein A from Staphylococcus aureus to the Fc portion of IgG molecules. Indeed, protein G has been proposed as a superior Fc binding protein due to its broader species reactivity. Thus, we have prepared a complex of protein G with particles of colloidal gold and determined its applicability for spot-blot analysis and postembedding immunolabeling by comparing it with protein A-gold complex. By spot-blot analysis no difference in binding of protein G-gold or protein A-gold to IgG molecules from a whole spectrum of animal species was observed. Moreover, using rabbit, sheep, or goat anti-rat albumin antibodies to detect nitrocellulose-immobilized rat albumin or antigenic sites in paraffin and Lowicryl K4M thin sections from rat liver, no difference was found with protein G-gold or protein A-gold. Similarly, no difference in binding to protein G-gold or protein A-gold was observed with a battery of monoclonal antibodies. However, in contrast to expectations, protein A gold reacted well with both sheep and goat IgG molecules; indeed, for the light and electron microscopic localization of albumin with sheep or goat antibodies it was as efficient as protein G-gold. These results demonstrate, therefore, that both protein G-gold and protein A-gold are useful second step reagents for immunolabeling and that protein G-gold was not a superior probe in the systems tested. PMID- 3327695 TI - Is cisplatin useful for breast cancer? PMID- 3327696 TI - Prostate cancer: evaluation of response to treatment, response criteria, and the need for standardization of the reporting of results. AB - Response criteria and the reporting of results in clinical trials on drug therapy of stage D prostate cancer were evaluated by examination of studies listed in the Index Medicus 1980-1984. During this 5-year period, 70 studies (51 phase II and 16 phase III) were listed, comprising 3184 evaluable patients. Among 346 patients reported as having evaluable disease according to the WHO criteria, 198 had well defined evaluable disease. A variety of response criteria were used, the NPCP criteria being the most frequent. Only three studies included solely patients with evaluable disease according to the WHO criteria. Reporting of results was often inadequate. The value of the most frequently used response parameters such as acid phosphatase, bone scan, per-rectal ultrasound, CT scan, bone pain and performance status is discussed. A system to standardise the reporting of results is proposed. PMID- 3327697 TI - Changes in haemodynamics and left ventricular function during intravenous nifedipine infusion with and without additional propranolol in patients with coronary artery disease. A randomized, placebo controlled trial. AB - The haemodynamic effects of a combined intravenous treatment of nifedipine and propranolol in ten patients with coronary artery disease compared to a single treatment with nifedipine or placebo were investigated. Nifedipine infusion resulted in a reduction of left ventricular (LV) afterload and LV volumes with an increase in heart rate and EF and no change of the double product, coronary sinus flow, LV diastolic parameters and dp/dtmax. Addition of propranolol lowers myocardial oxygen demand by reducing heart rate and dp/dtmax together with a sustained afterload reduction with no change in LV volumes and EF. The vasodilatatory action of nifedipine pretreatment balanced the negative effects of acute beta-receptor blockade on LV function and allows the reduction of myocardial oxygen demand without a deterioration of LV function. PMID- 3327698 TI - Disposition of monodesethylamodiaquine after a single oral dose of amodiaquine and three regimens for prophylaxis against Plasmodium falciparum malaria. AB - The disposition of monodesethylamodiaquine was studied in four healthy subjects after a single oral dose of 10 mg/kg amodiaquine base. Amodiaquine was not found in any sample, but the major metabolite monodesethylamodiaquine was detected and was assumed to be the sole derivative that contributed significantly to antimalarial activity in the blood. The best fit for the decay of the metabolite was obtained with a three-compartment model. The half-lives of the first two phases were 3.2 to 11.4 h for t1/2 alpha 1 and 22.7 to 50.3 h for t1/2 alpha 2 in plasma. The half-life of the terminal phase (t1/2 beta) was between 9 and 18.2 days. The concentration in whole blood was 4- to 6-times higher than in plasma. Three schedules (alternate days, weekly, daily) of the conventional prophylactic dose of 10 mg/kg per week were compared in six other healthy subjects. There were significant differences in the plasma monodesethylamodiaquine levels between the three schedules. PMID- 3327700 TI - Morphology and function of blood monocytes after incubation with lung surfactant. AB - Human blood monocytes were incubated for different periods of time with lung surfactant (phospholipid concentration 1-2.5 mg/ml). After short-term (30 min) incubation, there was an increase in the nitroblue tetrazolium (NBT) reduction of the monocytes both at rest and during stimulation with E. coli bacteria, and enhanced ingestion of fluorescein-labelled yeast particles. Electron microscopic examination of the same monocytes showed an active cell surface with numerous protrusions. Long-term (24 h) incubation with surfactant resulted in a reduced ability of the cells to adhere to plastic dishes. Although the NBT-reduction of resting monocytes was increased after long-term incubation with surfactant, the additional enhancement of NBT-reduction after stimulation with bacteria was decreased. These cells were rounded, usually devoid of surface structures, their nuclei were condensed, and their cytoplasm filled with surfactant material. Thus, monocytes are initially activated in the presence of surfactant, but if the cells become overfed with surfactant lipids their functional capacity decreases. PMID- 3327699 TI - Assessment of airway secretions by pulmonary function tests. PMID- 3327701 TI - Pulmonary manifestations of temporal arteritis. AB - Temporal arteritis is a well-recognized multi-systemic disease. Pulmonary manifestations, however, are extremely rare. In two patients with biopsy-proven temporal arteritis, lung involvement was observed. One patient presented with multinodular pulmonary lesions, while the second had a diffuse interstitial pattern. Both patients responded well to corticosteroid treatment. In a review of the literature, only four additional cases associating lung involvement with temporal arteritis were found. The possibility of primary pulmonary vasculitis should be considered in elderly patients with temporal arteritis. PMID- 3327702 TI - Proteolytic activity of human tumor cell lines deriving from bronchial squamous cell carcinoma, pulmonary metastasis of rhabdomyosarcoma and pleural metastasis of mesothelioma. AB - The proteolytic activities of human tumor cell lines deriving from bronchial squamous cell carcinoma, a lung metastasis of an embryonal rhabdomyosarcoma and a pleural mesothelioma were measured by use of chromogenic substrates. N-acetyl alanine aminopeptidase activity, plasminogen activator activity, H-D-Ile-Pro-Arg p-NA splitting activity as well as plasmin-like activity, cathepsin G-like activity and plasma-kallikrein-like activity were found in cell lysates. The enzymatic activity of N-acetyl-alanine aminopeptidase, plasminogen activator and H-D-Ile-Pro-Arg-p-NA splitting activity changed during culturing. Plasminogen activator and H-D-Ile-Pro-Arg-p-NA splitting activity decreased to very low values, whereas N-acetyl-alanine aminopeptidase activity leveled at 1 x 10(-5) mU/cell. Unlike other proteolytic activities, plasminogen activator was released into the medium. Plasminogen activator activity could be measured in culture medium which contained no fetal calf serum. PMID- 3327704 TI - The concept of the "perisinusoidal functional unit" of the liver--importance to pathological processes. AB - Non-hepatocytes account for 30 per cent of cells in the liver, with sinusoid coating endothelial and Kupffer cells being the most common types. In addition, there are some scattered pit cells in the wall. Ito cells (perisinusoidal cells, lipocytes) are located in the Disse space. In this paper a review is given of structural and functional changes of cells in response to pathological conditions with reference to the importance of such changes due to diseases of the liver and the organism in large. Cooperation and interaction among non-hepatocytes, the vascular pole of hepatocytes, and Disse space as the site of reaction are summarised under the concept of the "Perisinusoidal Functional Unit", and the concept is explained in greater detail by examples (lipoprotein catabolism, processes of phagocytosis, vitamin A storage, virus infections, accumulation of pathological substances, fibrosis, and capillarization). PMID- 3327703 TI - Duration of protection by oxitropium bromide against cholinergic challenge. AB - In order to determine the duration of action of the inhaled anticholinergic agent oxitropium bromide, a controlled study of the effect of pre-treatment with oxitropium bromide 200 micrograms against cholinergic challenge was carried out in ten asthmatic subjects (6 children, 4 adults). After baseline measurements of lung function (FEV1 and sGaw) and methacholine PC20 (the concentration of methacholine to produce a 20% fall in FEV1) oxitropium bromide or placebo were inhaled double-blind on 2 separate days. Lung function and methacholine PC20 were then measured at 1, 3 and 6 h post dosing. Oxitropium bromide caused significant protection from methacholine challenge for 6 h (p less than 0.05). PMID- 3327705 TI - The effect of hypoxia and hypokinesia on prostacyclin (PGI2) production of vessel wall. PMID- 3327706 TI - [Structural biochemical properties of the membrane of nucleus-free erythrocytes]. PMID- 3327707 TI - [Comparative characteristics of the pancreatic exocrine activity in rats of various ages]. AB - Activity of alpha-amylase, lipase and protease in the pancreatic gland homogenate was shown to be considerably depressed in 24-month old animals as compared with the 12-month old ones. The same was true for the pancreatic gland secretory response (juice volume, alpha-amylase, lipase and protease excretion) to administration of 0.1 N hydrochloric acid. PMID- 3327708 TI - [Down regulation of insulin receptors in the rat liver in aging]. AB - No decrease in the specific binding of 125I-insulin in the liver plasmatic membranes in response to insulin administration (2 units per 100 g/w) occurred in 24-26 month old rats whereas the response was obvious in 5-6 month old animals. The older animals showed a less obvious response of insulin receptors to 2-week administration of the hormone. PMID- 3327709 TI - Duke-Elder lecture. Retinal arteritis, retinal vasculitis and autoimmune retinal vasculitis. PMID- 3327711 TI - [Model of signal transduction through insulin receptors]. PMID- 3327712 TI - [Insulin resistance]. PMID- 3327710 TI - Air, methylcellulose, sodium hyaluronate and the corneal endothelium. Endothelial protective agents. AB - In a randomised trial the endothelial protective agent used during extracapsular cataract extraction and intraocular lens insertion was air in 19 eyes (group 1), methylcellulose in 25 eyes (group 2) and sodium hyaluronate in 22 (group 3). The cell population densities of each eye were estimated immediately before and three months after the operations to determine the degree of cell loss. Eyes showing mechanical (touch) damage on the second postoperative day were eliminated. The numbers of eyes in each group which showed a statistically significant cell loss were compared, and the mean cell losses in each group were tested for significant differences. It appears that air actually damages the endothelium while methylcellulose and Na-hyaluronate are not harmful, and afford a high, essentially equal degree of endothelial protection. PMID- 3327713 TI - [Transient neonatal thyroid dysfunction]. PMID- 3327714 TI - [The role of vitamin D in the abnormal action of parathyroid hormone]. PMID- 3327715 TI - [Localized bullous pemphigoid in a young adult]. PMID- 3327716 TI - Differences in growth factor sensitivity between primary and transformed murine cell cultures revealed by BrdU/Hoechst flow cytometry. AB - Spontaneous cell transformation is a common feature of all murine cell cultures grown in vitro for extended periods of time. During early passages, these cultures show either progressively reduced growth or complete cessation of growth; after such a 'crisis' they display increasing growth rates and unlimited lifespan. Here we use a novel bromodeoxyuridine/Hoechst flow-cytometric technique to examine the growth response of diploid and transformed cells of the murine species Micromys minutus under a variety of growth conditions. After spontaneous transformation, growth factor exposure results in increased G0/G1 cell recruitment and higher growth rates than shown by the nontransformed diploid cell fraction. Despite clonal heterogeneity, this difference is seen at all fetal calf serum (FCS) concentrations, although it is most pronounced with low serum. Epidermal growth factor and insulin are shown to act synergistically and promote growth equal to exposures of transformed cultures to 10% FCS. The observed differences in growth factor response between diploid and aneuploid cells could explain the reported lack of a classical growth crisis in growth factor supplemented media during the spontaneous in vitro transformation of primary cell cultures. PMID- 3327717 TI - Liver membrane antibodies in chronic delta hepatitis. AB - The correlation between the presence of liver membrane antibodies (LMA) and delta superinfection in chronic hepatitis B was studied in 136 chronic hepatitis patients, 20 hepatitis B surface antigen asymptomatic carriers and 50 healthy controls, by testing for the presence of LMA, hepatitis B virus markers and anti delta (anti-HD). Neither anti-HD nor LMA were detected in controls or in asymptomatic carriers. LMA positivity was statistically higher (p less than 0.001) in anti-HD-positive patients than in those with no anti-HD. Gamma globulin and glutamic pyruvic transaminase values were increased both in anti-HD- and LMA positive patients with respect to those who were negative. In conclusion, a close association between the positivity to anti-HD and the presence of circulating LMA was found. PMID- 3327718 TI - The histone H1(0)/H5 variant and terminal differentiation of cells during development of Xenopus laevis. AB - The maintenance of the differentiated condition is supposed to be associated with the presence of a histone of the H1(0)/H5 subclass. If the H1(0)/H5 variant has an important role in differentiation distinct from that of H1, it should display differential expression in time and position during development. Here we report that this prediction is verified during Xenopus laevis development, in which tadpoles exhibit a very characteristic, developmentally regulated pattern of histone H1(0)/H5 expression that is different for the derivatives of each embryonic germ layer. However, the pattern of appearance of this variant during development does not reflect a simple correlation between its presence and the state of differentiation. Therefore, these results are pertinent to current ideas on differentiation and the involvement of lysine-rich histones in the repression of eukaryotic genes. PMID- 3327719 TI - The enlarged retrozygomatic fossa: a case report of an anatomic variation. PMID- 3327720 TI - Self-assessed chewing ability of Finnish adults with removable dentures. PMID- 3327721 TI - [The Great October Socialist Revolution and the development of the main trends in human physiology]. PMID- 3327722 TI - Ring-like distribution of IgG-containing cells around the lymph follicle in the human intestine. AB - Immunoglobulin (Ig)-containing cells were studied in the lamina propria of the normal human large bowel and around the lymph follicle, including Peyer's patches, in the normal intestine. Ig-containing cells were identified by the indirect immunoperoxidase staining method, using mouse anti-human Ig monoclonal antibodies. In the lamina propria in the large bowel, the mean percentage of IgA+ (IgA1+ cells and IgA2+ cells), IgM+, IgD+, IgG+ and IgE+ cells was 75.9, 8.5, 7.3, 5.8, 2.5, respectively (total 100), namely there was a marked preponderance of IgA+ cells in comparison to IgG+ cells. However, IgG+ cells were observed not only on the epithelial but also in the serosal side of lymph follicles, showing a ring-like pattern. Ig+ cells of the other four classes did not show such a pattern. The ring-like distribution of IgG+ cells around lymph follicles was observed in both the large and small intestine including Peyer's patches. This tendency was observed in 9 out of 14 follicles (64.3 per cent). A large number of IgG+ cells were observed outside lymph follicles, while a small number of IgG+ cells were observed at the most outer rim of lymph follicles which suggested a local maturation of IgG+ cells. The significance and the role of the newly recognized IgG+ cells in the vicinity of lymph follicles remain to be resolved. PMID- 3327723 TI - The role of plasma secretin during starvation in dogs. AB - Plasma secretin levels were measured during a 72-hour starvation period in dogs. Plasma secretin rose significantly and insulin levels fell significantly during starvation. Intravenous glucose loading at the end of the 72-hour starvation period suppressed plasma secretin and free fatty acid levels with a concomitant rise of glucose and insulin levels. These findings suggest that secretin might be regulated by plasma glucose and insulin levels and might play a role in lipolysis during starvation. PMID- 3327724 TI - Low dose aminophylline accelerates recovery from diazepam premedication for digestive endoscopy. AB - The value of intravenous aminophylline in accelerating recovery from premedication with diazepam was assessed against placebo in a randomized, double blind trial. One hundred ten patients undergoing routine diagnostic upper gastrointestinal endoscopy received diazepam intravenously in a dosage sufficient to achieve adequate sedation. On completion of the endoscopy, patients received either aminophylline (1.5 mg/kg) or placebo. Recovery from sedation was assessed on clinical grounds by a nurse, objectively using a serial reaction time test, and by the patient on a visual analogue scale. The number of patients judged to be fully alert at 30 and 60 min after the procedure was significantly greater in the aminophylline group than in the placebo group. Compared with values obtained before sedation, the placebo group had significantly prolonged reaction times 30 min after completion of the endoscopy, whereas patients who received aminophylline did not. However, according to their self-assessments, patients in both groups felt more uncoordinated following sedation. Aminophylline appears to hasten recovery from sedation with diazepam, and its use may permit earlier mobilization of patients after endoscopy. PMID- 3327726 TI - [A service for the immunological typing of blood and bone marrow donors (work results and outlook)]. PMID- 3327725 TI - [Problems in the creation and use of a contingent of typed bone marrow donors]. PMID- 3327727 TI - [Serodiagnosis of the agent causing the acquired immunodeficiency syndrome (AIDS)]. PMID- 3327728 TI - [Work experience in the organization of a bank of typed cadaveric bone marrow]. PMID- 3327729 TI - [Association of HLA antigens with the intensity of the immune response to tetanus anatoxin]. PMID- 3327730 TI - Effects of reduced acid conditioning time on enamel microleakage. PMID- 3327731 TI - Gingival crevicular fluid response to subgingival composite resin restoration. PMID- 3327732 TI - Prefabricated post systems. PMID- 3327733 TI - Effectiveness of ultrasonic scalers: a literature review. PMID- 3327734 TI - A composite resin and gold onlay restoration. PMID- 3327735 TI - Correction of defective sibilant phonation created by a complete maxillary artificial denture. PMID- 3327736 TI - The dangers of do-it-yourself dentistry. PMID- 3327737 TI - Health implications of mercury in dental amalgam. PMID- 3327738 TI - Posterior composite resin: current trends in restorative techniques. Part 1: Pre preparation considerations, preparation, dentin treatment, etching/bonding. PMID- 3327739 TI - Basic intraoral suturing. PMID- 3327740 TI - Alternative sweeteners: a review. PMID- 3327741 TI - Steroids in third molar surgery: a review. PMID- 3327742 TI - Seating the cast restoration. PMID- 3327743 TI - Submandibular sialolithiasis. PMID- 3327745 TI - Resin-bonded bridge modification. PMID- 3327744 TI - Posterior composite resin: current trends in restorative techniques. Part 2: Insertion, finishing, and polishing. PMID- 3327746 TI - Untoward reactions to local anesthetics. PMID- 3327747 TI - Jan Evangelista Purkyne (1787-1869). PMID- 3327748 TI - Synthesis of an active hybrid growth factor (GF) in bacteria: transforming GF alpha/vaccinia GF fusion protein. AB - A hybrid gene encoding for a polypeptide consisting of the first 33 N-terminal amino acid (aa) residues of transforming growth factor-alpha (TGF-alpha) and a C terminus consisting of 20 aa residues of vaccinia growth factor (VGF) was chemically synthesized and expressed as a fusion protein in Escherichia coli. The primary structure of the hybrid gene product maintained the same positioning of the three disulfide bonds found in each parent molecule thus conserving the first two loop regions of TGF-alpha and the third loop region of VGF. After cleavage with CNBr its renatured biological activity was found to be comparable to TGF alpha and VGF with respect to binding to the epidermal growth factor receptor, stimulation of DNA synthesis and induction of anchorage-independent growth of NRK cells in the presence of TGF-beta. Thus, we suggest that similar domains can be interchanged within the same family of molecules and equivalent functionality maintained. PMID- 3327749 TI - Carbohydrate-binding protein 35: molecular cloning and expression of a recombinant polypeptide with lectin activity in Escherichia coli. AB - Affinity-purified antibodies directed against carbohydrate-binding protein 35 (CBP35), a galactose-specific lectin, were used to screen a lambda gt 11 expression library derived from mRNA of 3T3 fibroblasts. This screening yielded several putative clones containing cDNA for CBP35, one of which was characterized in terms of its expression of a fusion protein containing beta-galactosidase and CBP35 sequences. Limited proteolysis of lysates containing the fusion protein, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with anti-CBP35, yielded a peptide mapping pattern comparable to that obtained from parallel treatment of authentic CBP35. Such a limited proteolysis followed by affinity chromatography on a Sepharose column coupled with galactose also yielded a 30-kDa polypeptide that exhibited carbohydrate binding activity. This polypeptide can be immunoblotted with anti-CBP35, but not with antibodies directed against beta-galactosidase. These results indicate that we have identified a cDNA clone for CBP35 that yields a recombinant polypeptide with lectin activity produced in Escherichia coli. Using this cDNA clone as a probe, Northern-blot analysis showed an increased expression of the CBP35 gene when quiescent 3T3 cells were activated by the addition of serum growth factors. PMID- 3327750 TI - A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. AB - A set of genomic plasmid banks was constructed using the centromere-containing yeast shuttle vector YCp50. The centromere-containing vector is useful for the isolation of genes that are toxic to yeast when present in high copy number. Fourteen independent banks were prepared each with an average representation of two to three times the yeast genome. Any individual plasmid from a given bank is guaranteed to be of independent origin from plasmids obtained from each of the other banks. The banks were constructed from three different size classes of DNA fragments that resulted from varying conditions of partial digestion with Sau3A. This avoided the bias caused by differential sensitivity of sites to cleavage with Sau3A. Insert DNA is sufficiently large that most genes will be present in the set of plasmid banks at a frequency of about 0.1%. PMID- 3327751 TI - pUC12-W1: a plasmid vector for the study of cloned DNA conformation. AB - pUC12-W1 is a new cloning vector for the study of torsion-induced structural transitions of insert DNA. It was derived from pUC12 by deleting three A + T-rich sequences which can undergo structural transitions when torsionally stressed. Transitions at these sites have low energy of activation and undefined structures. They complicate studies on transitions of DNA inserts by diverting torsional force and causing the vector to be undefined in helical and energetic terms. The new vector pUC12-W1, from which these segments have been deleted, will facilitate studies of torsion-induced structural transitions of insert DNA. PMID- 3327752 TI - Expression of the alpha and beta tubulin genes of the African trypanosome in Escherichia coli. AB - The African trypanosome, Trypanosoma brucei, contains multiple genes for both alpha- and beta-tubulins, which code for similar if not identical proteins. Studies of the structure and function of trypanosome microtubules have been limited due to the difficulties in obtaining sufficient amounts of purified tubulin. To produce large amounts of purified tubulin for studies of structure and function and to begin developing a system for producing systematic alterations of tubulin structure we have cloned and expressed the alpha- and beta tubulin genes of T. brucei in Escherichia coli to produce the unfused proteins. Controlled high-level expression of both alpha- and beta-tubulin was achieved using a plasmid vector, pOTS, in which expression is controlled by phage lambda promoter/operator and a temperature-sensitive lambda repressor. The tubulins produced are insoluble, as has been found for many other proteins expressed to high levels in E. coli; they are readily purified to near homogeneity by chromatography on DEAE-cellulose in 7 M urea. N-terminal analysis of the purified proteins indicates that they are initiated correctly and that the N-formyl group is removed from the initiating methionine. This factor will probably prove important in the reconstitution of biologically active tubulin. PMID- 3327753 TI - High-copy-number and low-copy-number plasmid vectors for lacZ alpha complementation and chloramphenicol- or kanamycin-resistance selection. AB - Three types of alpha-complementation plasmid vectors were constructed which contain a chloramphenicol- or kanamycin-resistance (CmR or KmR) gene and polylinker cloning sites within the coding region of lacZ'. These vectors are essentially based on high- or low-copy-number replicons. The low-copy-number vectors, 3.61 kb in size, confer CmR and contain the pSC101 replicon and pUC8 /pUC9-type polylinker. On the other hand, the high-copy-number vectors, 2.21 to 2.68 kb in size, confer either CmR or KmR, and contain the pBR322 replicon and pUC18-/pUC19-type or other modified polylinkers. All cloning sites except HindIII and SmaI sites in the KmR vectors are unique in each plasmid. Since almost all frequently used plasmid vectors confer ampicillin resistance, these vectors may be useful to simplify the subcloning/DNA joining experiments due to unnecessity of radioisotope labelling, size fractionation and purification of foreign DNA segments. PMID- 3327754 TI - Isolation of an ompC-like outer membrane protein gene from Salmonella typhi. AB - We have isolated the structural gene for an outer membrane protein of Salmonella typhi, from a genomic library constructed in bacteriophage lambda 1059, using the Escherichia coli ompC gene as a heterologous probe. E. coli ompC codes for an outer membrane pore protein (porin) that is induced preferentially at high osmolarity and high temperature. The S. typhi ompC-like gene was subcloned in pBR322 and introduced into E. coli HB101 and into P678-54, a minicell-producing strain. In both strains it expressed a 38.5-kDa protein, which was incorporated into the outer membrane envelope and comigrated with an S. typhi outer membrane protein which was expressed both at low and high osmolarity in vivo. PMID- 3327756 TI - Anomalous dinucleotide frequencies in both coding and non-coding regions from the genome of the human malaria parasite Plasmodium falciparum. AB - We have statistically analysed the distribution of nucleotides and dinucleotides in 21 genes of the 81% A + T-rich human malaria parasite Plasmodium falciparum. The mRNA-synonymous strands of this protozoan show in general a marked excess of purines over pyrimidines, correlated with abnormally high levels of Lys and Glu. We have used the large differences in base composition between coding and non coding regions to estimate that the parasite possesses in the range of 2700-5400 genes. The dinucleotide preference patterns are compared with consensus patterns derived from other organisms [Nussinov, Nucl. Acids Res. 12 (1984) 1749-1763]. Patterns in the coding regions surprisingly resemble those of higher, rather than lower eukaryotes, particularly with respect to TG elevation and CG suppression. The latter is correlated with an abnormally low level of Arg in these parasites. In the non-coding regions, the four dinucleotides made up of C and/or G are found with significantly higher frequencies than expected (approx. 50-150%), specifically to the 5' side of the coding regions. The possible role of these dinucleotides in control sequences is discussed. PMID- 3327755 TI - Extracellular production of cloned alpha-amylase by Escherichia coli. AB - Overexpression of Bacillus stearothermophilus gene coding for thermostable alpha amylase in Escherichia coli was shown to cause outer-membrane damage leading to extracellular location of periplasmic proteins. Prolonged high expression of the alpha-amylase gene under lacZpo control eventually also lysed cells. Surprisingly, expression controlled by the pL promoter of phage lambda allowed specific release of periplasmic proteins into the growth medium without total cell lysis. Accumulation of alpha-amylase in the growth medium continued for at least 24 h under lambda pL control, whereas beta-lactamase activity ceased to increase beyond the exponential growth phase. The extent of outer membrane damage caused by alpha-amylase expression was monitored by following growth kinetics in the presence of lysozyme and by electron microscopy of the cells. Supplementing growth medium with Mg2+ restored the normal growth kinetics. It is suggested that periplasmic protein release caused by alpha-amylase overexpression is a stress response of the cell. A role for induced autolytic activity of the cell as a final effector of protein release is also proposed. PMID- 3327757 TI - Peripheral tissue insulin sensitivity in healthy elderly subjects. AB - To determine whether the decline in glucose tolerance with age is related to changes in peripheral tissue insulin sensitivity, 11 healthy older (65-85 years) and 12 healthy younger (20-38 years) subjects, matched for physical activity and body mass index, were studied. The glucose-insulin infusion technique, in which glucose and insulin are infused at constant rates over 150 min, was used to assess peripheral tissue insulin sensitivity. The metabolic clearance rate (MCR) of glucose, which reflects peripheral tissue insulin sensitivity, is derived from the resulting steady-state blood glucose. Fasting blood glucose was similar in the two groups, but mean blood glucose 2 h after an oral glucose load was higher in the older group. MCR of glucose expressed per kilogram lean body mass was almost identical in both groups (13.3 +/- 1.3 vs. 13.5 +/- 1.3 ml/kg lean body mass/min, respectively). Evidence of decreased glucose tolerance with normal peripheral tissue insulin sensitivity suggests that changes in other factors may be more important than previously recognised. PMID- 3327758 TI - [Characteristics of planning an experiment and multi-dimensional statistical analysis in determining the threshold and safe levels of toxic chemical substances]. PMID- 3327760 TI - [Methods of evaluating the health status of the population in relation to atmospheric air pollution by emissions from different industrial plants]. PMID- 3327759 TI - [Current hygienic aspects of the accumulation of persistent organochlorine pesticides in human biosubstrates]. PMID- 3327761 TI - [Use of tranquanalgesia as a method of anesthesia during the cerclage of the cervix uteri in pregnancy]. PMID- 3327762 TI - [Migration of spermatozoa]. PMID- 3327763 TI - [Selected cardiological problems in obstetrics. II. Arrhythmia, conduction disorders and arterial hypertension]. PMID- 3327764 TI - [Analysis of the incidence of recurrence in vaginal mycoses]. PMID- 3327765 TI - [Complete transverse vaginal septum. Case report and review of the literature]. PMID- 3327766 TI - Histochemical and immunohistochemical study of noradrenergic, serotonergic and peptidergic innervation of the cerebral circulation. AB - Using fluorescence histochemistry, we have examined the origin of noradrenaline (NA)-, 5-hydroxytryptamine (5-HT)- and neuropeptide Y (NPY)-containing perivascular nerve fibres supplying the major cerebral arteries of the gerbil, and the effect of superior cervical ganglionectomy on their cerebrovascular density and distribution. Bilateral ganglionectomy resulted in a complete loss of these perivascular nerve types in the anterior circulation, while a few fibres still persisted in the posterior circulatory bed. In addition, we demonstrate the presence of both 5-HT- and NPY-positive cell bodies in the superior cervical ganglion (SCG) of adult gerbils, suggesting that the main origin of cerebrovascular 5-HT- and NPY- (as well as NA-) containing nerve fibres is in the SCG. PMID- 3327767 TI - Orthodontic bonding. Direct bonding. PMID- 3327768 TI - Orthodontic bonding. Indirect bonding. PMID- 3327769 TI - Hemopoietic growth factors and oncogenes in myeloid leukemia development. AB - Most primary myeloid leukemias are dependent for proliferative stimulation on the glycoprotein colony-stimulating factors. These agents are therefore mandatory co factors in the development of myeloid leukemia. The CSFs also modify oncogene transcription, and in model leukemogenesis experiments GM-CSF has been shown to be a proto-oncogene. However, most evidence is against an autocrine hypothesis of myeloid leukemia based solely on CSF production by emerging leukemic cells. Because the CSFs also have differentiation commitment actions, they can induce differentiation in myeloid leukemic cells, and G-CSF in particular has an impressive capacity to suppress myeloid leukemic populations by this action. The antagonistic actions of the CSFs on myeloid leukemic cells make it difficult to predict whether they will prove to be useful agents in the management of myeloid leukemias. PMID- 3327770 TI - Amino acid substitution at position 13 of the N-ras gene in a non-Hodgkin's lymphoma patient. PMID- 3327771 TI - Leukemic colony-forming cells in acute myeloblastic leukemia: maturation hierarchy and growth conditions. PMID- 3327772 TI - Molecular properties and biological activity of human macrophage growth factor, CSF-1. PMID- 3327773 TI - Clinical implications of tumor heterogeneity. PMID- 3327774 TI - Treatment results in childhood AML, with special reference to the German studies BFM-78 and BFM-83. PMID- 3327775 TI - Formation of a hybrid bcl-2/immunoglobulin transcript as a result of t(14;18) chromosomal translocation. PMID- 3327777 TI - Long-term follow-up after therapy cessation in childhood acute lymphoblastic leukemia. PMID- 3327776 TI - The treatment of acute myelogenous leukemia. PMID- 3327778 TI - Progress in treatment of advanced non-Hodgkin's lymphoma in children--report on behalf of the Polish Children's Leukemia/Lymphoma Study Group. PMID- 3327779 TI - Strategies for the future chemotherapy of human immunodeficiency virus (HIV). PMID- 3327780 TI - Oncogenes: clinical relevance. PMID- 3327781 TI - Activation of the met proto-oncogene in a human cell line. PMID- 3327782 TI - Molecular-genetic analysis of myc and c-Ha-ras proto-oncogene alterations in human carcinoma. PMID- 3327783 TI - Monoclonal antibodies against the viral and human cellular myb gene product. PMID- 3327784 TI - Cancer genes generated by rare chromosomal rearrangements rather than activation of oncogenes. PMID- 3327785 TI - Intra-arterial cis-platinum in osteosarcoma. PMID- 3327786 TI - In vitro treatment of bone marrow from patients with T-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma using the immunotoxin WT1-ricin A. PMID- 3327788 TI - Use of autologous bone marrow transplantation in acute myeloid leukemia. PMID- 3327787 TI - Ablative therapy supported by autologous bone marrow transplantation with in vitro treatment of marrow in patients with B-cell malignancy. PMID- 3327789 TI - The use of cultured bone marrow cells for autologous transplantation in patients with acute myeloblastic leukemia. PMID- 3327790 TI - Bone marrow transplantation in leukemia in the absence of an HLA-identical sibling donor. PMID- 3327791 TI - Bone-marrow purging with monoclonal antibodies and human complement in ALL and AML. PMID- 3327792 TI - Purging of bone marrow with a cocktail of monoclonal antibodies (VIB-pool) for autologous transplantation. PMID- 3327793 TI - Autologous bone marrow transplantation in paediatric solid tumours. PMID- 3327794 TI - Cytokines with possible clinical utility. PMID- 3327795 TI - L-arginine methylester reduces Ca2+/Cl(-)-dependent L-[3H]glutamate binding and Ca2+-activated neutral protease activity in rat hippocampal membranes. AB - Specific binding of L-[3H]glutamate was measured in Tris-HCl buffer in rat hippocampal membranes. In these experimental conditions 1 mM CaCl2 induced an increase in binding due to an increase in Bmax. L-Arginine methylester did not modify the Cl(-)-dependent binding of L-[3H]glutamate, but it decreased Ca2+/Cl( )-stimulated binding in a dose-dependent manner, decreasing Bmax without changing KD. L-Arginine methylester reduced calcium-activated neutral protease activity in a dose-dependent manner. Serine protease inhibitors (aprotinin and di isopropylfluorophosphate) did not affect L-[3H]glutamate binding, whereas leupeptin reduced it in a dose-dependent manner. L-Arginine did not mimic the effect of L-arginine methylester in either model. PMID- 3327796 TI - Extrapituitary effects of corticotropin-releasing factor. AB - Corticotropin-releasing factor (CRF) has been identified in brain regions that participate in the regulation of the autonomic nervous system and behavioral responses. This paper summarizes the central nervous system as well as the peripheral effects of CRF that are different from those on the anterior pituitary. CRF acts within the brain to increase plasma concentrations of adrenaline and noradrenaline resulting in increased plasma concentrations of glucagon and in hyperglycemia. In the dog, CRF also acts within the brain to increase plasma concentrations of vasopressin. The intracerebroventricular administration of CRF results in a decrease of gastric acid secretion stimulated exogenously by pentagastrin and 2-deoxy-D-glucose or stimulated endogenously by a protein meal. CRF also acts within the brain to decrease gastric emptying and small intestinal transit but to increase large bowel transit and fecal excretions. The central administration of CRF produces hypertension, tachycardia and an elevated oxygen consumption. The effects of CRF on behavior are numerous. CRF induces a reduction in food intake, increases grooming behavior, locomotor activity, vocalization and induces an aroused state but decreases sexual receptivity. Intravenous administration of CRF decreases gastric acid secretion, gastric emptying and blood pressure but increases heart rate, plasma vasopressin concentrations, mesenteric and aortic blood flow, venous return to the heart and pancreatic bicarbonate and protein secretions. The physiological significance of these peripheral actions of CRF on various organ systems is not known.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327797 TI - Distribution of Immunoreactive CRH in man. PMID- 3327798 TI - Regulation of gene S-14 by triiodothyronine in liver. PMID- 3327800 TI - c-myc expression in the thyroid. I: Normal, adenomatous, and cancerous thyroid tissue. AB - Recent investigations have suggested that myc oncogene expression may be important in the development or progression of thyroid tumors. The purposes of the present study were to assess cellular (c)-myc expression in thyroid adenomas (n = 5), as well as in thyroid cancer (n = 4) and in normal thyrocytes (n = 7). Total RNA was prepared by extraction with guanididium thiocyanate and ultracentrifugation through a CsCl2 cushion. 30 micrograms total RNA was size fractionated on a 1% (w/v) agarose/formaldehyde gel and transferred to nylon membranes. These membranes were hybridized to a 32P-labelled third exon c-myc DNA. Following hybridization, blots were washed under high stringency and subjected to autoradiography; radioautographic bands were assessed visually or were quantitated by scanning densitometry. Nodular tissue had approximately the same degree of expression of the 2.4 Kb c-myc message as the surrounding normal tissue from the same gland (0.66 +/- 0.09 vs. 1.0 +/- 0.26, respectively); normal thyrocytes were capable in every instance of expressing the 2.4 Kb c-myc message. Thyroid cancer tissue expressed this message (0.91 +/- 0.17) but only at a level comparable to normal tissue. No other bands of hybridization were detected in any samples. We conclude that c-myc oncogene expression is comparable in normal thyrocytes and in thyroid nodules or thyroid cancer samples. These findings support a role for c-myc in both normal and neoplastic thyrocyte growth. PMID- 3327801 TI - c-myc expression in the thyroid. II: Thyrocytes and peripheral and intrathyroidal lymphocytes from patients with autoimmune thyroid disease. AB - Enhanced oncogene expression observed in lymphocytes from patients with systemic lupus erythematosus has suggested the importance of studying oncogene expression and regulation in the cellular events of autoimmune thyroid diseases (AITD). The present study examines oncogene expression in peripheral and intrathyroidal lymphocytes from patients with Hashimoto's disease (HD) and Graves' disease (GD). Intrathyroidal lymphocytes from a patient with primary thyroid lymphoma were also examined. Lymphocytes were isolated by Ficoll-Hypaque gradients, and total RNA was prepared by extraction with guanididium thiocyanate and ultracentrifugation through a cesium chloride cushion. RNA concentrations were determined by O.D. readings at 260/280 nm and each sample subjected to gel electrophoresis with ethidium bromide staining to assure the integrity of the RNA. 30 micrograms total RNA was size fractionated on a 1% (w/v) agarose/formaldehyde gel and transferred to nylon membranes. These membranes were hybridized with nick-translated 32P labelled c-myc DNA (exon III), washed at high stringency and subjected to autoradiography. Specific bands were quantitated by scanning densitometry. Five RNA samples from GD thyroids had 2.4 Kb bands corresponding to c-myc with a mean O.D. (+/- SD) of 0.76 +/- 0.23, whereas 7 from normal thyroid glands had mean O.D. of 1.0 +/- 0.26. Peripheral lymphocytes from 7 GD patients had a mean O.D. of 1.41 +/- 0.25, 4 HD patients had a mean O.D. of 1.05 +/- 0.10 and 2 normal patients had a mean O.D. of 1.4 +/- 0.14. The readings for a sample obtained from intrathyroidal lymphocytes of a patient with HD and thyroid lymphoma were 1.0 and 1.4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327802 TI - Relaxation, biofeedback training and cancer: an annotated bibliography, 1960 1985. PMID- 3327799 TI - Similarities and differences of steroid response elements. PMID- 3327803 TI - The human sex ratio. Part 2: A hypothesis and a program of research. PMID- 3327804 TI - Expression of two cross-reactive idiotypes on mouse antibodies against bromelain treated mouse erythrocytes. AB - Two cross-reactive anti-idiotype (Id) antibodies were previously prepared from sera of rabbits immunized with mouse monoclonal antibodies against bromelain treated mouse erythrocytes (BrMRBC). Most of the anti-BrMRBC plaque-forming cells (PFC) were suppressed by either of the two anti-Id antibodies. The Id profiles of anti-BrMRBC PFC were almost identical among various cell populations in a strain, but different among various mouse strains. Mouse sera contained both of the Id bearing immunoglobulins Ig, and a significant part of the Id-bearing Ig were eliminated by absorption with BrMRBC. Nude BALB/c mice were almost equal to normal BALB/c mice in the Id patterns of anti-BrMRBC PFC and in the concentrations of the Id-bearing Ig. The injections of anti-Id antibodies into suckling mice suppressed, specifically, the development of the B cells to produce the homologous Id-bearing Ig, but the injection of Id-bearing monoclonal antibodies barely affected Id expression. It is suggested that the two Id are encoded in germ-line genes of mice, and are expressed independently of each other and Id-anti-Id regulations by T cells or B cells. PMID- 3327805 TI - Restoration of the LPS responsive phenotype in C3H/HeJ macrophage hybrids: LPS regulation of hepatocyte-stimulating factor production. AB - The fusion of thioglycollate-elicited peritoneal macrophages from lipopolysaccharide (LPS) non-responsive C3H/HeJ mice to an HPRT-negative variant of the murine macrophage cell line P388D1 has resulted in the derivation of a series of macrophage hybrids. Following exposure to LPS, these hybrids now produce the cytokine hepatocyte-stimulating factor (HSF) which induces the synthesis of the acute-phase reactant alpha 2-macroglobulin in primary rat hepatocyte cultures. The concentration of extracellular HSF was dependent upon both the duration and amount of LPS, with optimal HSF being detected after 72 hr incubation with 10 micrograms/ml of LPS. Parallel LPS-stimulated cultures treated with 10(-6)M dexamethasone did not secrete detectable amounts of HSF. Both the molecular weight (29,000 MW), and the fact that HSF activity was not inhibited by an antiserum directed against murine interleukin-1 alpha (IL-1 alpha), suggests that HSF and IL-1 are distinct cytokines. Therefore, macrophage hybrids have been derived which have acquired the LPS-responsive phenotype and which synthesize the cytokine HSF following LPS stimulation. This phenotype appears stable since similar results have been observed with these hybrids after in vitro culture for over 8 months. PMID- 3327806 TI - Prevention of murine cerebral malaria by low-dose cyclosporin A. AB - The effects of cyclosporin A (CsA) were investigated in an experimental model of cerebral malaria. In this model, Plasmodium berghei ANKA-infected CBA/Ca mice develop a clinically and histologically characterized neurological syndrome which is considered to be the result of immunopathological reactions mediated by L3T4+ T cells. It was shown that CsA displayed a strong protective effect on neurological complications when given at a dose 1 mg/kg/day for 5 consecutive days (Days 4-8), which had no effect on the parasite. Paradoxically, this protection against neurological complications was not seen when parasiticidal doses were used during this limited 5-day period. A similar protective effect was observed with two CsA derivatives, C5-34 and H7-94. The mechanisms by which CsA and the two derivatives could prevent murine cerebral malaria are unknown but can be related to exquisite effects on some lymphocyte functions. In view of these results, it might be conceivable to investigate the benefits of using low doses of CsA in man, in conjunction with the classical antiparasite therapy, for the management of cerebral malaria. PMID- 3327807 TI - [Clinical usefulness of the lupus band test]. PMID- 3327808 TI - [Eosinophilic acropustulosis in infancy]. PMID- 3327809 TI - The activities of cytokines are pleiotropic and interdependent. AB - Many cytokines with multiple effects on the growth and functions of a wide variety of target cells have been discovered. Consequently, cytokines may exhibit considerable overlap in their biological effects on lymphoid, myeloid and connective tissue target cells. Even biologically distinct cytokines may have similar effects by initiating the production of a cascade of identical cytokines or of one another. The benefits of this apparent redundancy and interdependence of these activities remain to be established. Our information concerning cytokines is still far from complete, as illustrated by the recent characterization of a novel chemotactic cytokine and identification of a family of related mediators. PMID- 3327810 TI - Developmental change in the second half of life--strategies for modification of selected compartments of aging. AB - Age-related changes of different individuals multicentric and polymorphic. We have approached this problem of age-related changes by examining (1) membrane densities of receptors of various ligands in different organs, and (2) changes in different classes of T cells and of antibody response. Three strategies have been developed to modify progression of age-related changes to different extents in different compartments in which age-related changes occur. The first is based on administration of hormones, the second on administration of purine analogues and the third on administration of diets which differ in fatty acid content. Details of this last approach are reviewed in this paper. Lifespan of different species is a component of the evolution of each species. The variables which are decisive in the evolutionary processes which affect lifespans of different species are not necessarily variables which play a decisive role in the different health span of different individuals of the same species. For each individual of a given species, relative health span represents variations within the limits of the evolved lifespan of the species and depends on alleles of many different genes. PMID- 3327811 TI - Gene cloning and structure--function relationship of cytokines such as TNF and interleukins. AB - The genes for a number of proteins, potentially useful in cancer therapy and collectively called "biological response modifiers", have been cloned and expressed in micro-organisms in recent years. These recombinant proteins, which are now available in pure form in nearly unlimited quantities, include interferons, interleukins and cytotoxins such as Tumor Necrosis Factor (TNF) and lymphotoxin. Most often the human gene has been cloned and expressed, with view to possible applications in medicine, but usually the mouse equivalent gene was also characterized in order to carry out syngeneic animal model experiments. TNF is selectively toxic for many transformed cell lines, either alone or in combination with interferon or inhibitors of RNA or protein synthesis. Cells sensitive to the cytotoxic action of TNF and cells unaffected by it nonetheless usually carry about an equal number of TNF receptors; hence it is the secondary, intracellular signal which makes the difference between a transformed cell and a normal, diploid cell. TNF can induce a number of different genes in a variety of cells; for example, endothelial cells express a surface antigen responsible for adherence of leucocytes. Another gene which is induced by TNF is interleukin 6 (also called 26 kDa protein or BSF-2). This interleukin, IL-6, is a growth and differentiation factor for B cells as well as for T cells; it is responsible for functions previously ascribed to hepatocyte-stimulating factor, but has no interferon activity. The toxic action of TNF on tumor cells must involve the release of arachidonic acid as phospholipase inhibitors block the TNF-induced effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327812 TI - Cell stimulation by haemopoietic lymphokines. AB - Haemopoietic cells appear to respond to two distinct classes of growth factors, cell-bound molecules and lymphokines. Stimulation by lymphokines can be modelled by IL-3-dependent cell lines, and evidence is presented that such stimulation may represent a novel system of cell signalling unrelated to those where stimulation is a progression from a resting cell state into DNA synthesis and mitosis. The concept of a "rolling" cycle is introduced, and discussed in relationship to recent results suggesting that phosphorylation of a specific 33 kDa protein may be part of the control mechanism. Based on responses to different IL-3s, it is suggested that one function of lymphokines is to modulate responses to others by mechanisms other than regulation of receptor expression. PMID- 3327813 TI - Recombinant live virus vaccines. AB - Many successful vaccines are based on live attenuated viruses. An attractive idea is to genetically engineer these live attenuated vaccines so that they express protective antigens from other pathogens. Vaccinia virus, the smallpox vaccine, can be considered as the prototype for this sort of approach. Over one hundred examples of vaccinia virus recombinants are recorded in the literature and many of these have been shown to protect animals against challenge with the appropriate pathogen. Several problems need to be overcome before these recombinants can be tested in humans; however, the potential advantages of this approach ensure vigorous study of these difficulties. Vaccinia virus recombinants can also be used to dissect the cell-mediated and humoral immune responses to pathogens, and have thus proved to be valuable laboratory tools. However, it remains to be seen if they will also be used in other than experimental situations. PMID- 3327815 TI - Regulatory facilitation reaction and active tolerance: a non-euclidian view of the immune reaction authenticated by immunology of reproduction. PMID- 3327814 TI - The genetic origin of murine lupus-associated autoantibodies. AB - Systemic lupus erythematosus and rheumatoid arthritis in human and murine systems are characterized by circulating autoantibodies and immune complex deposition in various organs causing tissue damage and disease. To define the molecular and clonotypic origin of these anti-self responses, and to determine whether abnormalities in Ig genes or somatic mechanisms generating autoantibody diversity may contribute to lupus etiology, we performed molecular analyses of the Ig germline gene organization and the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice. Comparative restriction fragment length polymorphism analysis of a large number of Ig gene loci from autoimmune and normal mice indicated that (a) lupus can develop in different Ig heavy and kappa light chain variable region gene haplotypes, and (b) the Ig germline genes in lupus mice might be normal. To determine whether autoantibodies are encoded by unique Ig gene segments present in the normal germline repertoire, but not expressed in exogenous responses, we compared nucleic acid sequences encoding lupus autoantibodies and antibodies against foreign antigens. Similar, and in some instances even identical, gene segments were expressed in both types of antibodies, indicating that anti-self and anti-foreign responses use the same, or at least an overlapping, germline gene repertoire. A large variety of Ig variable, diversity, and joining gene segments encoded these autoantibodies with different specificities. Hence, the overall murine lupus-associated anti-self response may be essentially unrestricted. Furthermore, limited evidence has been obtained that both germline genes and somatically mutated genes encode autospecificity, making gross abnormalities in mechanisms for somatic mutation of Ig variable genes unlikely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327816 TI - Progress in the development of vaccines against parasitic diseases. AB - Vaccines for parasitic diseases have lagged behind the development of vaccines for important viral and bacterial diseases. Among the reasons for this is the extreme antigenic complexity of parasites and also the adaptive ability of parasites to co-exist with their host, often through modulation of the host's immune response. Advances in technology including in vitro cultivation, hybridoma and recombinant DNA methods have provided valuable tools for the study of parasite immunology and have resulted in major strides toward vaccines for several protozoan and helminth parasites. PMID- 3327817 TI - Neuroimmune interactions: experimental and clinical strategies. AB - This historical mini-review is devoted to the 30th Anniversary of the research activities of the Neuroimmunomodulation Group at the Immunology Research Center of Belgrade. During the past 30 years, these scientists have contributed to: (a) the definition of the structural and functional complexity and the lymphoneuroendocrine web of the immune microenvironment; (b) the structural and functional dissection of the neuron, brain and mind by means of anti-neural antibodies; (c) the antigenic relationship among the multiple components of the nervous and lymphoid tissues; (d) the methodological and conceptual aspects of the influence of lesioning and stimulation of various brain structures on immune responsiveness; (e) the lymphoneuroendocrine relationships during embryonic development; (f) the definition of immunopsychiatric diseases, i.e., neural tissue immunologic hypersensitivity in psychiatric diseases; (g) the immunomodulating and regulating activity of methionine-enkephalin and leucine enkephalin; (h) the correlations between associative learning and immunity (behavioral immunology). The theoretical, experimental and clinical devices created, and observations collected from 1957 to 1987 by the Belgrade group of neuroimmunologists proved to be useful for elucidation of the complex interactions between the immune system and the nervous system, and provided a broad perspective for research in neuroimmunomodulation. PMID- 3327818 TI - Melatonin: a principal neuroimmunoregulatory and anti-stress hormone: its anti aging effects. AB - Major environmental variables such as daily and seasonal changes of light and temperature regulate the daily circadian variations of synthesis and release of the pineal neurohormone N-acetyl-5-methoxytryptamine (melatonin). Melatonin has now been shown to be a potent immunoregulatory agent, and to be able to antagonize the immunosuppressive effects of acute anxiety stress in mice, as measured by antibody production, by thymus weight, and by the capacity of stressed- and evening-melatonin-treated mice to react against a lethal virus. Both psychogenic factors and infectious agents such as viruses can act as "stressors" and induce an immunosuppression. Their combination is a determinant for the course of infectious diseases and, perhaps, cancer. Circadian (evening) melatonin possesses thus the singular ability to up-regulate the immunosuppression of stressed mice. This effect of melatonin is not exerted directly on immunocompetent cells, but mediated via the endogenous opioid system upon antigen-activation of T cells. Melatonin being a short-lived hormone with negligible side-effects which is rapidly degraded and eliminated by the body, the use of melatonin offers a new approach to the physiological control of stress and stress-related infectious diseases. In addition, melatonin could be used for the potentiation of primary immunization (vaccination) against antigens of the most varied nature which do not evoke a robust or longlasting secondary (memory) response. The regulatory function of pineal melatonin is discussed also in relation to hematopoiesis, to its oncostatic effects, and to its possible dual role in reproduction physiology and generation of immunocompetence and tolerance during ontogeny. PMID- 3327819 TI - Natural and synthetic peptides (other than neuropeptides) endowed with immunomodulating activities. AB - A large number of peptides, in most cases of low or relatively low molecular weight, exert immunomodulating activities, i.e., they interact in vitro with various cell populations of the immune system and, in vivo, enhance or depress, according to the case, cell-mediated and humoral immune functions. Immunomodulating peptides include glycopeptides from the bacterial cell wall, natural acyloligopeptide ciclosporin, peptidic hormones from the thytide cyclosporine, peptidic hormones from the thymus, peptidic fragments of immunoglobulins and other plasma proteins, as well as peptides isolated from food proteins. An amazing diversity of structure exists among the various immunomodulating peptides. The molecular mechanisms of interaction between these peptides and the cells of the immune system remain, in most cases, to be elucidated. Possibilities of therapeutic applications exist for many of these immunomodulating peptides: one of them (ciclosporin) is widely used as an immunosuppressive drug, several others (glycopeptides, lipopeptides, tuftsin, thymic peptides) are under clinical investigation as immunostimulating and/or immunorestoring agents. PMID- 3327821 TI - Adherence of Klebsiella to human buccal epithelial cells. PMID- 3327820 TI - Comparison of betamethasone dipropionate (0.05%) and betamethasone valerate (0.1%) ointments in psoriasis and other dermatoses--a multicentric double-blind clinical study. PMID- 3327822 TI - Susceptibility of Klebsiella pneumoniae to heavy metal ions in vitro. PMID- 3327823 TI - Orbituary of Lt. Col. V. Rangachari. PMID- 3327824 TI - Infant and childhood mortality. PMID- 3327826 TI - Farber's lipogranulomatosis. PMID- 3327825 TI - Genes and neoplasms. PMID- 3327827 TI - [Organic mineralized allografts]. PMID- 3327828 TI - [Coronoplasty of teeth supporting a removable partial denture]. PMID- 3327829 TI - [Esthetic presentation]. PMID- 3327830 TI - [Dental surgery in the Royal Navy from the 18th century to the present]. PMID- 3327831 TI - [Composite resin restorations and leakage. An in vitro study of the marginal seal between the restoration and root dentin]. PMID- 3327832 TI - [Taking the 1st impressions: psychological aspects in the child]. PMID- 3327833 TI - [Instrument dynamics applied in closed and curved canals in endodontics]. PMID- 3327834 TI - An investigation into the bond strength between a root canal sealer and root filling points. PMID- 3327835 TI - Prostacyclin and hemolytic uremic syndrome: from the laboratory to an international registry. PMID- 3327836 TI - Prognosis after donor nephrectomy: an update. PMID- 3327837 TI - Silicon and chronic hemodialysis patients. PMID- 3327838 TI - Oxygen free radicals in nephrology. AB - For living creatures with an aerobic metabolism, the univalent reduction of oxygen can lead to formation within the cell of intermediate products with marked chemical instability and strong potential toxicity. These are the free radicals (FR) superoxide and hydroxyl, hydrogen peroxide and the singlet 1O2. Their toxicity is primarily expressed through the peroxidation of membrane lipids, resulting in mitochondrial, lysosomal and parietal damage. It is enhanced by the presence of metals in trace amounts. Imbalance between the production of FR and the availability of FR scavengers (superoxide dismutase, catalase, glutathione peroxidase, etc.) may underlie different human pathologies. FR have been thought to play a part in inflammation, the aging process, carcinomatous transformations, damage due to recirculation and autoimmune diseases. As far as the kidney is concerned, the intervention of FR has been demonstrated or can be postulated in various contexts in the light of what has been observed in other pathologies: immunological nephritis, toxic nephropathies, microthrombotic and microangiopathic processes, damage caused by post-ischemic reflow, and problems in the preservation and rejection of transplants. FR have also been incriminated in lung lesions following intradialytic leukostasis and some aspects of toxicity ascribable to uremia. Subject to the precautions imposed by the need for theoretical, experimental and clinical verification, FR biochemistry offers new keys to the interpretation of a variety of kidney pathologies and opens up new prospects for treatment, both through a better understanding of the mechanism of action of drugs already known and employed, and with regard to the practical possibility of using alternative or combined forms of therapy. PMID- 3327839 TI - Leprosy in children. PMID- 3327840 TI - Is pemphigus herpetiformis an entity? AB - Clinical, histologic, and immunofluorescence studies were performed in 15 patients with pemphigus herpetiformis. The initial diagnosis was dermatitis herpetiformis, IgA linear bullous dermatosis or bullous pemphigoid. The histology varied depending on the character of skin lesions, and showed eosinophilic spongiosis or slight acantholysis and/or polymorphonuclear papillary microabscesses. Direct immunofluorescence showed invariably intercellular IgG staining, and indirect immunofluorescence on monkey esophagus substrate was positive, at some periods, in five cases. About half of the patients responded to therapy with sulfones and prednisone, and only one patient responded to sulfones alone. Half of the patients required combined therapy with prednisone and cyclophosphamide or with higher doses of prednisone. In consecutive relapses, nine patients retained the pattern of pemphigus herpetiformis: in the others, lesions were mostly of pemphigus seborrheicus-foliaceus type. PMID- 3327841 TI - Of asklepiads, quacks, and early caretakers of the skin. PMID- 3327843 TI - Bereavement research in Israel--a critical review of the literature. PMID- 3327842 TI - Conjugal bereavement and immunity. PMID- 3327844 TI - Current state of research in the field of bereavement. PMID- 3327845 TI - Oral salbutamol vs fenoterol in childhood asthma. AB - A study to compare the effects of single oral doses of salbutamol (4 mg) and fenoterol (5 mg) was carried out in 22 asthmatic children aged 6-14 years. The patients received both drugs sequentially on two consecutive days within a week in a randomized, double-blind, crossover fashion. Peak expiratory flow rate, spirometry, flow-volume loops and whole body plethysmography were performed basally, at half-an-hour and hourly from 1 through 6 h. In 17 cases, all four pulmonary tests were performed also 8 h after drug administration. No significant difference in bronchodilator power was observed. Both drugs produced a significant increase in heart rate, which was more pronounced after fenoterol. These data suggest that, at the doses used, salbutamol may be a preferable choice. PMID- 3327847 TI - [Hemihypertrophy in a boy with polycystic kidney]. AB - Ultrasonographic and radiological examination of a male newborn with a mass in the left lumbar region revealed bilateral polycystic kidneys. At the age of 6 months, a moderate hemihypertrophy of the left side was detected and confirmed with 2 1/2 years. Growth, development and renal functions are normal. The association of hemihypertrophy with nephroblastoma is well known, with polycystic kidneys, however, very rare. PMID- 3327846 TI - Effect of high doses intravenous IgG in newly diagnosed diabetic children. AB - A controlled trial was carried out on type I diabetic children in order to evaluate the clinical effect of high doses intravenous gammaglobulins (i.v. IgG). Twenty newly diagnosed patients were admitted to the trial, ten of whom received 400 mg/kg body weight of i.v. IgG on 5 consecutive alternate days and subsequently after 15 days and monthly thereafter for up to six months, while ten patients served as controls. Insulin requirement in the treated and untreated groups was essentially similar at the start of the trial (0.94 +/- 0.47 vs 1.11 +/- 0.28) but showed a statistically significant difference at 3 (0.40 +/- 0.28 vs 0.66 +/- 0.26), 6 (0.36 +/- 0.19 vs 0.63 +/- 0.27) and 9 (0.38 +/- 0.20 vs 0.62 +/- 0.25) months. The difference was still evident at 12 months but no longer reached statistical significance. The reduced requirement of insulin was accompanied by a parallel increase in the C-peptide serum levels. Lymphocyte subpopulations, C3 and C4 and immune-complex levels did not show any significant modification after i.v. IgG administration. PMID- 3327849 TI - Biochemical and physiological indicators of selenium status in animals. AB - Selenium (Se) concentrations in animal tissues vary with the tissue and with the amount and chemical form of Se in the diet. In cattle, sheep and swine, Se concentrations rank in kidney greater than liver greater than heart greater than skeletal muscle greater than adipose tissue. Selenium concentrations (wet basis) in skeletal muscle of swine (.03 to .52 ppm) reflect natural dietary Se concentrations ranging from .03 to .49 ppm. Inorganic Se additions to diets low in natural Se (.05 ppm) increase skeletal muscle Se concentrations until dietary Se levels are adequate. After a period of Se repletion, skeletal muscle Se concentrations should be at least .08 ppm on a wet basis. Selenium concentrations in plasma, serum or whole blood are also related to inorganic Se intake and rise in direct relation to each other in the deficient to adequate range. Plasma or serum Se concentrations of .08 to .12 ppm are consistent with dietary adequacy. Selenium-dependent glutathione peroxidase (GSH-Px) activity of plasma or whole blood may also be used to assess Se status in some animals since plasma or whole blood Se concentrations are positively correlated with GSH-Px activity in animals that are low to adequate in dietary inorganic Se. However, inter-laboratory variation in GSH-Px values is large, and it is doubtful that limits of normalcy developed in one laboratory are applicable in others. In certain tissues it is important to distinguish between GSH-Px and glutathione (GSH) S-transferases, which can reduce organic hydroperoxides but which are not Se-dependent. It is also important that the instability of GSH-Px be considered so that losses in activity during handling and storage may be minimized. Urinary Se excretion and Se retention as percentages of Se intake may be helpful in assessing Se status when facilities for metabolism studies are available. PMID- 3327848 TI - Biochemical and physiological indicators of mineral status in animals: copper, cobalt and zinc. AB - The value of estimates of trace element requirements or of data on tissue trace element content for identifying and controlling trace element-related disorders is often limited by inadequate data on the relationships of such criteria to physiological performance. Investigations of metabolic events initiating early pathological responses to deficiency are beginning to suggest more effective indicators of physiologically relevant abnormalities in trace element intake or status. Progress in studies of metabolic responses to deficiencies of copper, cobalt and zinc is reviewed. PMID- 3327850 TI - Interactions of calcium, phosphorus, magnesium and vitamin D that influence their status in domestic meat animals. AB - Known and possible interactions between Ca, P, Mg, parathyroid hormone (PTH), calcitonin (CT), vitamin D and its metabolites, and interactions of each of these with other factors plus complexities and possible variations between and within domestic animal species, such as age, sex, physiologic state (i.e., pregnancy, lactation and growth) and diet, make Ca, P and Mg metabolism extremely dynamic and complex. Many advances have been made in understanding these interactions and how each of these factors is controlled, secreted or metabolized within the body. Some interactions among these factors are discussed in detail, mostly with a view to understanding mechanisms by which homeostasis of Ca, P and Mg is maintained. Also, three of the major diseases of mineral metabolism of cattle (milk fever, grass tetany and wheat pasture poisoning) provide excellent models to study the complex soil, plant and animal interrelationships among Ca, P, Mg and the factors that influence and control the ultimate utilization of these minerals in animals. These diseases are used to illustrate some of the interactions among many of the factors that influence Ca, Mg and P metabolism in domestic animals. PMID- 3327851 TI - Assessment of cadmium, lead and vanadium status of large animals as related to the human food chain. AB - Cadmium (Cd) and lead (Pb) are of established toxicological significance for humans, and it is important that intakes from foods not cause excessive exposure. Both elements concentrate to high levels in liver and kidneys of large, domestic food animals (cattle, sheep and swine), and Pb also concentrates in bone, which is sometimes used in the form of bone meal as a dietary supplement. Milk is a significant source of Cd and Pb for infants and toddlers. Levels of these elements in domestic food animal tissues and milk are presently within acceptable ranges for human consumption. Vanadium (V) sources to animals may increase and create potential human food problems; however, at the present time meats and milk are safe to consume with respect to this element. PMID- 3327852 TI - Hair analysis as an indicator of mineral status of livestock. AB - Despite several inherent characteristics that would appear to make hair a useful biopsy tissue, many problems make interpretation of data derived from hair analysis difficult. Endogenous minerals are incorporated into hair by several routes. Most attention on hair mineral incorporation has focused on element uptake within the hair follicle. Minerals incorporated within the follicle are presumably chemically or physically associated with cortical cells of the hair shaft and reflect mineral status at the time that the hair filament was synthesized. Because hair follicles in most species regularly go through cycles of intense metabolic activity and quiescence, mineral incorporation through the follicle is not a continual process. Mineral deposition onto hair does not cease when the follicle is not producing a hair fiber. The hair shaft is continuously exposed to several elements through contact with secretions from sebaceous, apocrine and eccrine glands. Significant quantities of major and trace elements of endogenous origin are adsorbed onto the hair surface via these secretions, especially when hair growth is not occurring or is very slow. For several elements significant correlations exist between mineral concentrations in hair and mineral intake. These correlations, however, are usually quite low. Non dietary factors such as sex, age, hair color, sire, body location and contamination affect mineral levels in hair. Dietary intake of calcium, phosphorus and iron are also known to affect uptake of other elements in hair. Because many factors cause variation in mineral content in hair, hair analyses are not precise indicators of mineral status. Hair mineral analyses may be useful, however, when combined with other indicators of mineral status to provide a more precise assessment of mineral status in livestock. PMID- 3327853 TI - Ovarian response to pregnant mare serum gonadotropin and porcine pituitary extract in gilts actively immunized against gonadotropin releasing hormone. AB - Two experiments were conducted to determine the effect of exogenous gonadotropins on follicular development in gilts actively immunized against gonadotropin releasing hormone (GnRH). Four gilts, which had become acyclic after immunization against GnRH, and four control gilts were given 1,000 IU pregnant mare serum gonadotropin (PMSG), while four additional control gilts were given saline. Control animals were prepuberal crossbred gilts averaging 100 kg body weight. Control gilts given saline had ovaries containing antral follicles (4 to 6 mm in diameter). Control gilts given PMSG exhibited estrus and their ovaries contained corpora hemorrhagica and corpora lutea. PMSG failed to stimulate follicular growth in gilts immunized against GnRH, and ovaries contained regressed corpora albicantia and small antral follicles (less than 1 mm in diameter). Concentrations of luteinizing hormone (LH) and estradiol-17 beta (E2) were non detectable in gilts immunized against GnRH and given PMSG. In the second experiment, five gilts actively immunized against GnRH were given increasing doses of PMSG every third day until unilateral ovariectomy on d 50. PMSG failed to stimulate follicular growth, and concentrations of follicle stimulating hormone (FSH), E2 and LH were not detectable. Six weeks later, gilts were given a booster immunization and then were given 112 micrograms LH and 15 micrograms FSH intravenously every 6 h for 9 d. The remaining ovary was removed on d 10. Although LH and FSH concentrations were elevated, administration of gonadotropins did not stimulate follicular growth or increase E2 concentrations. These results indicate that neither PMSG or exogenous LH and FSH can induce E2 synthesis or sustain follicular development in gilts actively immunized against GnRH. PMID- 3327855 TI - First complete description of the aspirin idiosyncrasy-asthma-nasal polyposis syndrome (plus urticaria)--1922 (with a note on aspirin desensitization). By F. Widal, P. Abrami, J. Lermoyez. PMID- 3327854 TI - Comparison of nifedipine with a new calcium channel blocker, flordipine, in exercise-induced asthma. AB - Four patients with documented exercise-induced asthma (EIA) were pretreated orally in random, double-blind fashion with the calcium channel blockers nifedipine 20 mg and flordipine 25 and 50 mg and placebo, then subjected to exercise challenge on a cycloergometer. Each patient served as his own control, undergoing exercise challenge with the different pretreatments on 4 separate days. No statistically significant protection from EIA was found with either nifedipine or flordipine. PMID- 3327856 TI - Plasma histamine after methacholine, allergen, and aspirin challenges. AB - Plasma histamine levels were measured by radio-enzymatic technique in seven patients following 10 challenges: five methacholine challenge tests, four antigen inhalation challenge tests, and one oral aspirin challenge test. Baseline plasma histamine was the same in all patients except in the aspirin-challenged patient, who had a higher baseline histamine level. There was no statistical change in the level of histamine throughout the test in either the methacholine-challenged or the antigen-challenged patients, whereas there was a marked increase in histamine levels in the aspirin challenged patient. A possible explanation is that methacholine and antigen are inhaled and therefore have primarily local effects on the lung, whereas oral aspirin has a systemic effect with consequently systemic changes in histamine which are detectable as changes in plasma level. PMID- 3327857 TI - [The adhesion of metallic structures treated with tin oxide (O.V.S.) using wettability technics]. PMID- 3327858 TI - [Tensile strength of bonded metal frameworks]. PMID- 3327859 TI - [Composites. 1: Traditional composites]. PMID- 3327860 TI - [Effect of dentin structure on the adhesion of a composite resin]. PMID- 3327861 TI - Growth factors involved in haemopoiesis. PMID- 3327862 TI - The rearrangement of cytoskeletal systems in epithelial cells accompanying the transition from a stationary to a motile state at the start of epithelial spreading. AB - The changes in the alignment of F-actin bundles in epithelial cells were studied, mainly using NBD-phallacidin, as the isolated corneal epithelium started to spread along the surface of Millipore filter. The epithelial cells at the margin were found to make the transition from a stationary to a motile state in two steps: first, from polygonal cells, in which F-actin was deposited along the cell border, to hemispherical cells, in which F-actin was distributed homogeneously along the inner cell surface; and second, from the hemispherical cells to spread cells in which F-actin bundles ran radially or in parallel to each other through the leading lamella from a cytocentre to the edges, as in fibroblastic cells. During the second step, an amorphous mass of F-actin was transiently accumulated at the distal end in the half-extended lamella and structured into bundles during development of the lamella. Since this proceeded only on substrata to which marginal cells could make contact firmly enough to enable the cells to extend, it was concluded that F-actin bundles were aligned within extending lamellae in relation to the tension exerted by the lamellae, and might be associated with other components to be microfilaments. PMID- 3327863 TI - The microtubule-organizing complex and the Golgi apparatus are co-localized around the entire nuclear envelope of interphase cardiac myocytes. AB - In most animal cells, the microtubule-organizing centre (MTOC) and the Golgi apparatus (GA) are co-localized on one side of the nucleus, an arrangement that allows these cells to acquire a functional polarity. An exception has been reported in the skeletal muscle myotube, where the MTOC and GA exhibit a circumnuclear distribution. We wished to determine if this unusual distribution of the MTOC and GA was peculiar to syncytial myotubes or reflected a pattern found in muscle cells generally. Immunofluorescence microscopic studies of cultured chicken skeletal muscle, cardiac muscle and gizzard smooth muscle cells were carried out using preimmune sera that recognized the pericentriolar material, anti-tubulin antibodies to label the MTOC, and fluorescent wheat-germ agglutinin to label the GA. These studies have shown that cardiac myocytes possess a circumnuclear distribution of their MTOC and GA as do skeletal myotubes, but smooth muscle cells exhibit the centrosomal MTOC and GA distribution found in most other cells. The circumnuclear MTOC/GA distribution therefore is associated with striated muscle cells. We also found that as embryonic cardiac myocytes pass through the cell cycle the microtubule-organizing activity in these cells switches from a circumnuclear distribution in interphase to the conventional centrosomal location during mitosis. Thus, cardiac myocytes provide a rare example of mononucleated animal cells that do not display a centrosomal MTOC or a polarized GA, and also reveal a system in which the MTOC structure can be reversibly altered in a cell cycle-dependent manner. PMID- 3327865 TI - Characterization of a heat shock-induced insoluble complex in the nuclei of cells. AB - The formation of an insoluble complex in isolated nuclei incubated at physiological temperature (37 degrees C) is demonstrated. A similar complex is shown to form in the nuclei of intact cells subjected to temperatures that induce the classical heat-shock response. The formation of this complex occurs rapidly in response to hyperthermia and is induced by small increases in temperature both in vitro and in vivo. We have characterized the formation of the complex in isolated nuclei and the nuclei of intact cells. A small number of the subset of nuclear proteins involved in the complex have been identified. The significance of the loss of solubility of these proteins in the nucleus following hyperthermia is discussed. PMID- 3327864 TI - Expression of c-myc during differentiation of the human teratocarcinoma cell line Tera-2. AB - The quantity of c-myc mRNA was measured during the retinoic-acid-induced differentiation of the pluripotent human teratoma cell line, Tera-2 cl. 13. As the cells were exposed to retinoic acid for longer periods of time the duration of the cell cycle progressively increased (measured by the rate of S phase entry) until the cells were effectively quiescent and expressed characteristic differentiation markers. Under these circumstances steady-state levels of c-myc expression increased by up to 1.6-fold with respect to rapidly growing undifferentiated cells. Southern blot analysis of the c-myc genes in Tera-2 indicated no major rearrangement or amplification in the cell line. PMID- 3327866 TI - Lampbrush chromosomes. PMID- 3327867 TI - Assay, purification and characterization of a recombinant malaria circumsporozoite fusion protein by high-performance liquid chromatography. AB - The immunodominant repeat region of the malaria circumsporozoite protein from Plasmodium falciparum was purified from a recombinant Escherichia coli to study as a potential subunit vaccine. The recombinant protein, R32Leu-Arg, is composed of 32 tetrapeptide repeat sequences from the circumsporozoite protein (R32) linked to the dipeptide, Leu-Arg. R32Leu-Arg was purified by a series of precipitation steps including temperature, ammonium sulfate, and acid pH treatments; followed by reversed-phase high-performance liquid chromatography (RP HPLC). An automated RP-HPLC assay was developed to measure the R32Leu-Arg concentration during both fermentation and purification. This assay was used in a variety of applications including measurement of production levels of the antigen during fermentation, evaluation of the protein purification process, quantitation of protein recovery, and as one criterion of protein purity. With minimal changes, the assay conditions were easily adapted to the semi-preparative level to produce 200 mg of purified product. The purified product was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; amino acid composition; and analytical size-exclusion and RP-HPLC. PMID- 3327868 TI - Specificity of the immunoadsorbent used for large-scale recovery of interferon alpha-2a. AB - After immunoaffinity chromatography, interferon alpha-2a synthesized in bacteria is not homogeneous. Beside oligomers and monomers, a fragment of molecular weight 15,000 was observed. Amino acid analysis and the determination of the amino terminal amino acid sequence of the fragment indicate that this polypeptide represents an interferon alpha-2a molecule lacking the 22 terminal amino acids. In order to define the epitope on the interferon alpha-2a molecule recognized by the immunoadsorbent, the binding to the immunoadsorbent of interferon alpha-2a fragments prepared by cyanogen bromide cleavage was studied. The results suggest that cyanogen bromide fragments Arg 22-Met 59 and Lys 112-Met 148 are recognized. Since the oligomers, the monomers and the fragment of molecular weight 15,000 of interferon alpha-2a share these sequences, the different forms are as expected co purified on the immunoadsorbent. PMID- 3327869 TI - Characterization of adsorption on the stationary phase using high-performance immunoaffinity chromatography. AB - Low-level adsorption on the stationary phase has been studied using immunochemical reagents. An immunoaffinity column has been evaluated using affinity-purified radioisotope-labeled monoclonal antibodies. Recovery experiments including continuous immunosorbent monitoring have been performed. Proper characterization of an immunoaffinity separation can result in the recovery of immunologically active material in high yield. PMID- 3327870 TI - The pathology of lymphoreticular and genital tissues of silvered leaf monkeys (Presbytis cristata) experimentally infected with Wuchereria bancrofti. AB - The discovery of the silvered leaf monkey, Presbytis cristata, as a suitable experimental host for the human filarial parasite, Wuchereria bancrofti, opened the door for major advances in our understanding of the disease caused by this parasite. To study the pathogenesis of bancroftian filariasis in this model, 15 adult P. cristata which had been experimentally infected with 250 infective third stage larvae of the parasite were examined. After inoculation with larvae, the monkeys were maintained under study for periods of 2 to 3 years, at which time all had achieved patent infections. At necropsy, Wuchereria-induced macroscopic lesions were not detected in experimentally infected monkeys. Microscopic findings included nematodiasis, microfilariasis, lymphadenitis, lymphangiectasis, perilymphangitis, splenitis, orchitis, periorchitis, epididymitis and funiculitis. Sections of normal adult worms were most often found in lymphatic vessels near lymph nodes, or in the lymphatics of the male genital system. These worms caused microfiliariasis in some regional lymph nodes. Inflammatory responses to filariae were most prominent in proximity to degenerated and dead worms, whereas intact, normal appearing adult worms elicited only minimal cellular response. PMID- 3327871 TI - Effects of trypsin on the in situ identification of epidermal cell membrane antigens. AB - In this work the role of trypsin in revealing epidermal cell surface antigens, with the use of immunological markers, was investigated. Two monoclonal antibodies (MCA) were used, the first: D47, belongs to the first cluster of differentiation and recognizes a membrane antigen of human thymocytes; the second HLA-ABC-m3, is an anti-HLA-B27 MCA. Preliminary treatment with various concentrations of trypsin was performed on frozen skin sections and followed by indirect immunofluorescence. D47 reacted with epidermal dendritic cells only after trypsin pretreatment of skin sections. In addition a mild preliminary trypsinization was shown to increase in situ immunoreactivity of MCA HLA-ABC-m3 with epidermal cells. Best results were obtained when trypsin concentrations ranging from 2.5 to 5 micrograms/ml were applied for 10 min at 37 degrees C. Preliminary trypsinization may be of interest for a better exposure of some surface antigens to immunohistochemical markers. PMID- 3327875 TI - [Lasers applied to the treatment of glaucoma (excluding trabeculoplasties with the argon laser)]. PMID- 3327873 TI - [Acanthamoeba keratitis. Clinical, histological and ultrastructural study]. AB - Acanthamoeba keratitis is a rare but very severe necrotizing stromal keratitis due to a non-parasitic free-living soil and freshwater amoeba. It affects more readily soft and hard lens wearers. It is often clinically mistaken for herpetic keratitis because of the similarity of the signs and the difficulty in performing the specific microbiological tests. This is the reason why the diagnosis is most often made at the time of penetrating keratoplasty and histological study of the buttons with special stains. Medical treatment is effective only when starting at the beginning of the disease. PMID- 3327877 TI - [Maturation of immature teratomas of the ovary. Apropos of a case and review of the literature]. AB - We report a case history of a 20 year old woman, primiparous, who had an immature teratoma of the ovary that developed. In June 1982 the diagnosis of an ovarian tumour of the right ovary was made after she had complained of pain in her pelvis, of metrorrhagia and ascites had been discovered. At that time we removed her right tube and ovary. There were no other lesions in the abdomen. The anatomopathological examination of the specimen revealed an immature grade II teratoma. She received six cycles of chemotherapy which consisted of a combination of Bleomycin, Velbe and Cysplatin between July and December. A second look laparotomy was carried out in February 1983. This showed that she had multiple secondary diffuse peritoneal lesions. Because of this total hysterectomy with the removal of the other tube and ovary and omentectomy were carried out. Histological examination showed lesions of a mature teratoma-grade 0. In October 1986 ultrasound showed two parenchymatous lesions in the liver. These were removed and the anatomopathological study showed that these were mature teratomata, identical to those that had been found at the second-look laparotomy. The patient is now considered to be cured after being free from trouble for the last 58 months. Looking through the international publications on these conditions has turned up 40 similar cases. The phenomenon of maturation seems to be of a good prognosis as compared with those where the teratomas stayed immature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327878 TI - [Value of a meiotic study of male sterility]. AB - Both in men where the somatic karyotype is abnormal as well as in cases where it is normal, it is worth while studying meiosis in the male. The picture of meiosis has been studied in the main from testicular biopsies and also partly from spermatic line cells found in sperm. Studying the haploid portion of the male pronucleus using the hamster test reflects the process of meiosis. In this way it has been possible to individualise different pathological entities such as asynapsis or desynapsis, alterations in synaptic complexes, the presence of several nucleoli or micronucleoli in the pachytene stage, hyper or hypo polidies, the presence of univalents and the breakdown of bivalents, oligochiasmatasis, chain or ring pictures or early desynapsis of the sexual vesicle in the diacinesis and in the first metaphase stage. Aneuploidies have been found in the second metaphase stage or when carrying out chromosome analysis on the male pronucleus. The abnormalities in the number of chromosomes which are found with the formula 47,XXY, may be due to faults in spermatogenesis, but in the case of the double Y in 47,XYY the extra Y will rarely be found during meiotic divisions. The Robertsonian translocations causing abnormalities in structure are due to the formation of trivalents whereas reciprocal translocations give rise to the idea of quadrivalent pictures mainly associated with faults in spermatogenesis. Finally, autosomal chromosome translocations seem to have more severe meiotic repercussions, particularly in cases where the inactive autosomal X chromosome is involved. Even where a somatic karyotype is normal in a fertile subject that does not mean that there is no meiotic abnormality present, because 8-10% of the cells that were studied showed such an abnormality. PMID- 3327872 TI - Isoelectric focusing of basic proteases in immobilized pH gradients. AB - By exploiting a new, alkaline immobilized pH gradient spanning the pH 10-11 interval, it has been possible to focus and to detect, by in situ zymogramming with cellulose acetate foils impregnated with fluorogenic substrates, 2 alkaline proteases, namely elastase and trypsin. Elastase gave a sharp array of 3 bands, with the following pIs (at 10 degrees C): 10.60 (major component), 10.53 (intermediate species) and 10.45 (minor isoform). Trypsin was resolved into 2, about equally abundant, species having pIs of 10.70 and 10.53. However, the latter enzyme gave smears in between these 2 forms and also anodic to the lower pI species. As hydrophobic interaction with the Immobiline matrix was excluded, it is suggested that these smears represent product of auto-digestion due to the very alkaline pH during the focusing process. PMID- 3327876 TI - [The priority of the surgical treatment of ovarian cysts or dispute with the Anglo-Saxons]. AB - It seems likely the first oophorectomy which was carried out in France must have been in the years 1847-1848 (Woyeikowsky and Vaullegard). This surgical procedure, however, was carried out much earlier. In Germany Chrysmar carried out the operation in 1819 and Ephraim McDowell in America, in Kentucky, did it in 3 cases between 1809 and 1816. Whereas Robert Houstoun operated on a woman in Glasgow in 1701, he did not carry out oophorectomy but punctured the cyst through a laparotomy incision. PMID- 3327874 TI - [Endophthalmos caused by intravitreal caterpillar hairs. Treatment by direct photocoagulation with argon laser]. AB - We describe an infrequent case of endophthalmitis due to intraocular caterpillar hairs. We report a notable decrease of inflammation after Argon laser photocoagulation of the caterpillar hairs. We also present optical and electronic microscope photographs of one of the hairs extracted from the patient's conjunctiva. PMID- 3327879 TI - [Echographic diagnosis of cystic hygroma. Apropos of a case]. AB - A case of nuchal cystic hygroma associated with non immune hydrops fetalis and renal malformation in one of two twins observed at 18th week of gestation is reported. Occurrence of acute polyhydramnios and severity of the anomalies showed by serial ultrasound scans has led to termination of pregnancy induced by prostaglandin E. This rare malformation is related to an abnormality of the lymphatic system and is usually associated with monosomy 45 XO or Turner syndrome. But a review of some 191 reported cases shows that this condition may be connected with various chromosomic or congenital anomalies. This may worsen the prognosis and accurate diagnosis is mandatory to guide the genetic counseling for future pregnancy. Ultrasonography allows precise diagnosis of cystic hygroma as soon as the end of the first trimester. The potentially lethal associated malformations and anomalies of karyotype will condition the management of this malformation. The prognosis usually fatal in utero will often lead to termination of pregnancy. PMID- 3327880 TI - [Ovarian pregnancy. Apropos of 32 cases]. AB - Ovarian pregnancies usually are diagnosed by the trophoblast which has gone into the ovarian tissue being found histologically. These pregnancies usually suggest haemorrhage from the corpus luteum or a rupture of ovarian cysts. The average age at which they appear is 29, just as it is the age for tubal pregnancies, but they do differ because there are few signs of infection and of infertility, and there are more multipara and women who are wearing an IUD. Two-thirds of ovarian pregnancies are on the peritoneal surface or in the hilum, away from the corpus luteum, and one-third are situated on the scar of the follicular ostium and have later infiltrated into the follicle. Most of these cases can be explained by reflux of the oocyte into the peritoneum. PMID- 3327882 TI - Somatomedins/insulin-like growth factors and fetal growth. PMID- 3327881 TI - [Long-term results of the treatment with physical agents exclusively in a series of cancers of the uterine cervix. Cooperative study of 1,383 cases]. AB - The authors present a study of 1,383 cases of invasive carcinoma of the cervix treated exclusively by radiotherapy between 1970 and 1981. Combination external radiotherapy followed by intra-cavitary applications was carried out. The study was carried out in 9 different radiotherapy centres in France using the same protocol and the same recording systems. The therapeutic results which have been recorded at every stage are among the best obtained until now, with 90% success for stage I after 5 years, 80% success for stage II, 52% for stage III growths. Only 2.1% failures occurred in the cervico-vaginal region. Pelvic recurrences were 7% in stage I and IIA, 14% in stage IIB and 24% in stage III. These recurrence rates are lower than have generally been recorded. Complication rates are also low and became less as the study continued, thanks to better use of dose distribution in individual cases which took note of doses received by neighbouring organs. The prognostic value of lymphography was analysed. PMID- 3327883 TI - Treatment of cryptosporidiosis with spiramycin in AIDS. An "N of 1" trial. AB - We describe a randomized, double-blind, placebo-controlled, crossover trial with spiramycin in a single patient with acquired immune deficiency syndrome (AIDS) and a severe secretory diarrhea caused by cryptosporidium. Spiramycin, a potentially harmful antibiotic, had no clinical or microbiological effect in this patient. The application of the single patient (N of 1) trial to common clinical problems is a simple way to analyze the value of different therapeutic approaches. The time-consuming, expensive, multi-patient trial with ultimate extrapolation to the individual patient can be avoided. Single-patient trials can influence management and improve patient care and have potentially wide use in patients with gastrointestinal disease. PMID- 3327884 TI - Comparison of ranitidine and cimetidine ulcer maintenance therapy. AB - We used published results from clinical trials to evaluate the efficacy of ranitidine and cimetidine as maintenance therapy following healing of acute duodenal ulcers. Only studies in which patients were treated with an evening-meal or bedtime dose of ranitidine (150 mg) or cimetidine (400 mg) over a 12-month period were used. The results from the analysis of seven clinical trials where ranitidine was directly compared to cimetidine indicated that 8.4% fewer patients experienced an ulcer recurrence on ranitidine (p less than 0.01). The estimate of the common odds ratio was 1.63, which indicated higher odds of recurrence versus nonrecurrence for cimetidine than ranitidine patients. The 95% confidence interval for the odds ratio ranged from 1.21 to 2.21. When data from placebo trials were included in the analysis, ulcer recurrence was 6.8% lower for ranitidine than for cimetidine (p less than 0.01). PMID- 3327885 TI - Immunosuppressant therapy of inflammatory bowel disease. Pharmacologic and clinical aspects. AB - The history of immunosuppressant drug use, both azathioprine (Aza) and 6 mercaptopurine (6-MP), in inflammatory bowel disease (IBD) over the past 20 years is briefly reviewed. The two drugs appear identical in their pharmacologic and biologic effects. Azathioprine is converted to 6-MP while in the body. Conflicting reports on the effectiveness of Aza have been published. The major National Cooperative Crohn's Disease Study (NCCDS) has found no advantage in Aza over placebo. In contrast, 6-MP was found to be effective in a large randomized trial. The shortcomings of the NCCDS reports are discussed with possible explanations for their negative findings. Our own studies, dating from 1968, are reviewed with 38 patients having been treated for up to 18 years, always in combination with small doses of steroids. Our results with Aza are similar to those of Present and Korelitz with 6-MP; about 70% of previously intractable patients improved substantially. Both Aza and 6-MP bring about healing and closure of most fistulas. Side effects can be serious but are usually manageable and, to some extent, preventable by appropriate dosage schedules. Since Aza has been approved for another benign, presumably autoimmune disease--rheumatoid arthritis--and because of its extensive use in other autoimmune diseases, we prefer to use Aza in selected patients with Crohn's disease who have failed to respond to more conventional modes of therapy. The use of immunosuppressants in ulcerative colitis is less clearly indicated. PMID- 3327886 TI - Gallbladder perforation. An imaging analysis. AB - We evaluated the radiologic studies of 23 patients with surgically or autopsy documented gallbladder perforation. Extravasation was shown by cholescintigraphy and cholangiography in seven patients and corresponded to free perforation or large pericholecystic loculation. In 16 patients, ultrasonography and computed tomography detected fluid and abscesses outside the gallbladder ranging from 1 to 2 mm pericholecystic fluid collections to large phlegmonous masses. A right, upper-quadrant mass on plain films and scattered calcification in this area suggested perforation. Gallbladder perforation could be diagnosed or suspected preoperatively in ten patients and antemortem in 22 of 23 individuals. This rate of recognition, higher than previously reported, may be ascribed in part to improvements in biliary imaging. PMID- 3327887 TI - Aortogastric fistula from hiatal hernia ulcer. A cause of massive upper gastrointestinal bleeding. AB - An 83-year-old woman with no history of vascular surgery presented with a fatal upper gastrointestinal bleed from an aortogastric fistula secondary to a penetrating gastric ulcer. The fistula was between the thoracic aorta and the gastric ulcer in a hiatus hernia. On autopsy, a discrete 1-cm ulcer had perforated into the otherwise normal thoracic aorta. Aortogastric fistula involving the thoracic aorta and a gastric ulcer is rare in the absence of vascular graft surgery or aneurysm. We review the pertinent literature. PMID- 3327888 TI - Serological examinations of HIV-I virus in Sudan. AB - 1614 blood samples from men and women in the Upper Nile region, Melut district (southern Sudan) were examined for HIV-antibodies. 109 samples were positive twice in the ELISA test, and 18 (1.1%) were confirmed by the IFT and Western Blot test. PMID- 3327889 TI - Serological examination for HIV-I antibodies in Nicaragua, Columbia and El Salvador. AB - 22 of 182 sera samples from Nicaragua, 6 of 111 samples from Columbia, and 25 of 388 samples from El Salvador were positive in the ELISA test. 37 of the 53 positive sera samples were positive again in a further ELISA test, and 1 of them was positive in the IFT and Western Blot test. PMID- 3327890 TI - A comparison of serological tests for the detection of HIV-antibodies. The clinical and serological course of one AIDS patient with seroconversion. AB - 240 serum samples originating from various AIDS risk groups were tested for HIV antibodies comparing an immunofluorescence test with the Western Blot and ELISA methods. In 95% of cases the results of the Western Blot and the immunofluorescence test were in accordance. In 12 samples the immunofluorescence test yielded positive results whereas there was no reaction in the Western Blot. Four of the sera were confirmed by the RIPA and yielded results which were in conformity with the immunofluorescence findings. A noteworthy case is a patient under observation since 1975 who had repeatedly shown negative Western Blot results but positive immunofluorescence responses and who had developed already marked clinical manifestations of AIDS. These findings indicate that the immunofluorescence test, employed as a confirmation method, is comparable to the Western Blot in its specificity (95.6%) but superior as far as sensitivity is concerned. Simplicity of performance and duration of test are the same for the immunofluorescence test and ELISA. PMID- 3327891 TI - [Solid tumors of the renal parenchyma in the adult. Does the absence of symptoms modify the prognosis?]. AB - Of 220 solid tumors of renal parenchyma reviewed, 26% (57 tumors) were asymptomatic and discovered by chance, either by radiology (45.5%), ultrasound (21%), biology (16%), clinical (10.5%) or histopathology examination (7%). The asymptomatic tumors were benign in 20% of cases whereas this was the case with only 3% of symptomatic tumors. For a given age, asymptomatic malignant tumors were in a less advanced stage than symptomatic tumors. These findings suggest the need for routine investigation for renal tumor syndromes. Whenever possible and whatever the indication for an examination. PMID- 3327893 TI - [Late results of the endourethral injection of Teflon in urinary stress incontinence]. AB - Results are presented after 2 and 4 years of follow up of 20 women with urinary stress incontinence treated by endourethral injections of teflon. Good results were obtained in 6 cases, the other 14 women obtaining no benefit, and it is concluded that the method is of little effectiveness. PMID- 3327892 TI - [Results of the double-blind use of an alpha blockader, nicergoline, in cervico prostatic dysfunctions]. AB - A double-blind prospective trial investigated effects of Nicergoline on micturitional disorders in 60 selected patients with dysuria in the absence of prostate hypertrophy and neurologic disease. Results evaluated from 29 men treated with the product and 25 receiving placebo, taking into account functional improvement and urinary output variations, showed a statistically significant improvement in patients in the Nicergoline group. PMID- 3327894 TI - [Premature ejaculation]. AB - Premature ejaculation (PE) is important in the sexual relations of couples. After emphasizing that certain PE are of curable etiology (eg. short frenum of prepuce), the different stage of PE are analyzed and classified as a function of the severity, and in consequence the reversibility, of the repercussions of the life of couples. A therapeutic technic is described that is based on the target proposed by Masters and Johnson. PMID- 3327895 TI - [Renal myeloid metaplasia. Value of the cytologic puncture of the kidney. Apropos of 2 cases]. PMID- 3327896 TI - [Reconstruction of the urinary tract before kidney transplantation]. PMID- 3327897 TI - [Medullasin]. PMID- 3327899 TI - [Progress in biological mass spectrometry--the history and prospects]. PMID- 3327898 TI - [Acidic proteins involved in calcification of tooth or shell]. PMID- 3327901 TI - [Ethanol fermentation in bacteria]. PMID- 3327900 TI - [Glycophospholipid-linked membrane proteins]. PMID- 3327902 TI - Endoscopic hemostasis of active upper gastrointestinal hemorrhage by local injection of adrenalin. PMID- 3327904 TI - The sealing ability of injection-molded thermoplasticized gutta-percha with and without the use of sealers. PMID- 3327905 TI - Leakage evaluation in vitro of two calcium hydroxide and two zinc oxide-eugenol based sealers. PMID- 3327903 TI - Impaired glucose counterregulation after insulin-induced hypoglycemia in thalassemic patients. PMID- 3327906 TI - Pain suppression after pulpectomy with preoperative flurbiprofen. PMID- 3327907 TI - Pioneers in endodontics. PMID- 3327909 TI - List of publications: Journal of the Formosan Medical Association. 1946-1986. PMID- 3327910 TI - Plasma zinc level in hemodialysis, continuous ambulatory peritoneal dialysis and renal transplantation. PMID- 3327908 TI - Is asthma increasing? PMID- 3327911 TI - Aspergillosis of the brain: report of an autopsy proven case. PMID- 3327912 TI - Endometriosis of the urinary bladder: report of a case. PMID- 3327913 TI - A rapid and efficient method for plasmid transformation of Klebsiella pneumoniae and Escherichia coli. AB - A rapid and efficient method for plasmid transformation of Klebsiella pneumoniae M5a1 and Escherichia coli K12 has been developed. The method, which uses a freeze thaw cycle in the presence of CaCl2 to facilitate DNA uptake, is substantially more efficient for K. pneumoniae M5a1 than the conventional transformation procedure for E. coli. The simplicity and speed of the method makes it very attractive for routine transformation of K. pneumoniae M5a1 and E. coli K12. PMID- 3327914 TI - A mutant of Candida albicans deficient in beta-N-acetylglucosaminidase (chitobiase). AB - A mutant of Candida albicans ATCC 10261 was isolated that was defective in the production of beta-N-acetylglucosaminidase (chitobiase). The mutant grew normally in minimal medium supplemented with either glucose or N-acetyl-D-glucosamine (GlcNAc) as carbon and energy source, and the cells formed germ-tubes at 37 degrees C when induced to do so with GlcNAc. However, unlike the wild-type parent strain, the mutant strain did not utilize N,N'-diacetylchitobiose for growth. The mutant and parent strains had similar growth rates on glucose or GlcNAc, similar rates of uptake of these sugars and similar rates of 14C-labelled amino acid incorporation. The chitobiase mutant did, however, contain 53-85% more chitin than the wild-type strain. No reversion of the mutant phenotype was observed following induction of mitotic recombination with UV light, suggesting that the mutant allele (chi) was carried homozygously in the chitobiase-deficient mutant. Although the chitobiase-deficient mutant was pathogenic, it was not as virulent as the wild-type strain. PMID- 3327915 TI - Purification and characterization of chloramphenicol acetyltransferase from Flavobacterium CB60. AB - From the highly chloramphenicol-resistant cytophaga-like bacterium Flavobacterium CB60, which can both acetylate chloramphenicol and degrade it in co-metabolism, the chloramphenicol acetyltransferase (CAT) was purified to homogeneity and characterized. The purification included fractional precipitation with ammonium sulphate and two affinity chromatography steps, eluting CAT the first time with 5 mM-chloramphenicol and the second time with a linear gradient (0-10 mM) of chloramphenicol. The purification was 3979-fold. Properties of this CAT were investigated and compared with CATs from other bacteria. Although CAT from Flavobacterium CB60 shares some properties with the enzymes from Escherichia coli and other Gram-negative bacteria--especially with CATII and CATIII--it has distinct properties like extreme heat lability and the inability to produce diacetylchloramphenicol, so that it might be regarded as a new variant. PMID- 3327916 TI - Production of long-chain alcohols by yeasts. AB - Fourteen yeast strains from six genera were analysed for the presence of long chain alcohols. Six strains from three genera contained long-chain alcohols, highest levels being found in Candida albicans. The alcohols were identified and determined by TLC, GLC and GLC-MS. The major long-chain alcohols synthesized by these organisms were saturated, primary alcohols with C14, C16 or C18 chain length. Unsaturated long-chain alcohols were not detected. In all strains that produced long-chain alcohols, the relative proportions were C16 greater than C18 greater than C14. Long-chain alcohol contents were higher in organisms from anaerobically, as compared with aerobically, grown cultures reaching about 650 micrograms (g dry wt organisms)-1 in stationary-phase cultures of C. albicans. In cultures of C. albicans, synthesis of long-chain alcohols occurred only after the end of exponential growth. The alcohols were predominantly present as free alcohols. The fatty-acyl chain-length profile of the triacylglycerol and to a lesser extent the sterol/wax ester fractions from C. albicans reflected that of the long-chain alcohols produced by this yeast. PMID- 3327917 TI - Hexagonal periodicity in the outer membrane of Bacteroides buccae. AB - In Bacteroides buccae, a hexagonally arranged periodic structure was found in the outer membrane (OM), in addition to hexagonal lattices present in its external surface layer (S-layer). This crystalline OM protein (COMP) was present as patches on the concave fracture face (the outer leaflet) of the OM in freeze fractured cells. Occasionally, hexagonally arranged structures could also be seen on the convex fracture face of the OM as 'fingerprints' of the COMP. The OM proteins were isolated and analysed by gel electrophoresis. The major band protein had an apparent molecular mass of 17 kDa. Whether the minor band proteins are also components in the structure of the COMP remains to be elucidated. Other oral Gram-negative anaerobic rods studied did not show any periodicity in their OM. PMID- 3327918 TI - Formation of a new cell wall by protoplasts of Candida albicans: effect of papulacandin B, tunicamycin and Nikkomycin. AB - Incorporation of polysaccharides into the walls of regenerating protoplasts of Candida albicans was followed in the presence of papulacandin B, tunicamycin and nikkomycin. With the first drug, chitin was incorporated normally whereas incorporation of glucans and mannoproteins was significantly decreased. Tunicamycin decreased incorporation of all wall polymers when added at the beginning of the regeneration process but blocked only mannan and alkali insoluble glucan incorporation when added after 5 h. Nikkomycin inhibited chitin synthesis, and the walls formed by the protoplasts were enriched in alkali soluble glucan. Pulse-chase experiments suggested that a precursor-product relationship between the alkali-soluble and alkali-insoluble glucans existed in the wall. The results obtained with the antibiotics were confirmed and extended by cytological studies using wheat-germ agglutinin labelled with colloidal gold and concanavalin A-ferritin as specific markers of chitin and mannoproteins respectively. The results support the idea that regeneration of walls by protoplasts occurs in two steps: firstly, a chitin microfibrillar skeleton is formed, and in a later step glucan-mannoprotein complexes are added to the growing structure. The chitin skeleton probably allows the orderly spatial arrangement of the other polymers giving rise to the regenerated cell wall. PMID- 3327920 TI - Toxic trace elements associated with airborne particulate matter: a review. PMID- 3327921 TI - A review of sampling methods for polyaromatic hydrocarbons in air. PMID- 3327919 TI - Biologically active compounds from plants with reputed medicinal and sweetening properties. AB - Examples are presented of plants with folkloric reputations that have recently afforded constituents with great potential for use as drugs or pharmaceutical excipients. Described are the results of laboratory investigations at this institution on the biologically active compounds of four plants with reputed medicinal properties and of six sweet plants used by local populations in various regions of the world. It is concluded that folklore information should be considered seriously in programs designed to yield prototype, biologically active molecules from plant sources. PMID- 3327922 TI - The sizes of particulate sulfate and nitrate in the atmosphere--a review. PMID- 3327923 TI - Acid particles and the tracheobronchial region of the respiratory system--an "irritation-signaling" model for possible health effects. PMID- 3327924 TI - Variability of hemodynamic parameters in young healthy subjects with and without hypertensive family history. PMID- 3327925 TI - The sympathetic nervous system response to stress in chronic vitamin E-deficient rats. AB - This study was undertaken to examine whether some stressful conditions affected urinary output of catecholamine of 3- and 18-month-old vitamin E-deficient rats and control rats. Basal levels of urinary norepinephrine (NE) and epinephrine (E) excretion of aged vitamin E-deficient rats was 2- to 3-fold higher than those of control rats. In both groups of young rats, cold exposure, administration of insulin, and immobilization stress provoked a marked increase in urinary output of NE, E, NE and E, respectively. However, the urinary catecholamine responses to these stresses were markedly diminished in aged rats. No significant changes were observed in excretion of catecholamine during these stresses in aged rats receiving vitamin E-deficient diet. Therefore, these results suggested that the responses of sympathetic nervous activity to these stresses were significantly lowered in the chronic vitamin E-deficient rats compared to control rats. PMID- 3327926 TI - Effect of short-term consumption of a high fat diet on glucose tolerance and insulin sensitivity in the rat. AB - The mechanism by which the consumption of high fat, low carbohydrate diets impair glucose tolerance and decrease insulin sensitivity is poorly understood. In an attempt to clarify this question, intravenous glucose tolerance and insulin action in the liver and skeletal muscle were examined in rats after two weeks feeding of either a high fat (HF: 66% energy as fat) or a low fat (LF: 12% energy as fat) diet. Both diets had a P/S ratio (ratio of polyunsaturated to saturated fat in the diet) of 1.3. The high fat diet resulted in mild impairment of intravenous glucose tolerance. Postprandial glucose levels were elevated in the presence of a sustained insulin response. In vitro insulin-stimulated glucose utilisation was decreased significantly in soleus muscle of HF rats, as indicated by decreased [14C]glucose incorporation into muscle glycogen. In contrast, muscle lipogenesis from glucose was not affected by dietary composition. There was no difference in insulin binding to soleus muscle of HF and LF rats, indicating a dissociation between insulin receptor binding and post-receptor metabolic events. Dietary composition did not influence the incorporation of increasing [14C]glucose loads into muscle glycogen or lipid in vivo. However, the HF diet was associated with reduced incorporation of [14C]glucose into lipids and glycogen in the liver and, to a smaller extent, reduced incorporation into adipose tissue lipids in vivo. These results suggest that the mechanism by which HF diets impaired glucose tolerance was mainly hepatic in origin. Decreased glucose uptake, secondary to reduced glucokinase activity, may result in a reduction in glucose utilisation in the liver. PMID- 3327927 TI - Vasopressin is increased in mineralocorticoid-induced blood pressure increase in man. AB - Vasopressin has been studied intensively in DOCA-salt rats and seems to play an important role in this model of hypertension. In the present study we investigated plasma vasopressin in seven normotensive young volunteers during the early phase of mineralocorticoid-induced hypertension. We administered 0.8 mg/day fludrocortisone for 1 week. Body weight, blood pressure, plasma vasopressin, plasma osmolality and electrolytes, as well as plasma renin activity, were evaluated on days 0, 3 and 7. Blood pressure increased significantly from 117/67 to 121/76 mmHg (P less than 0.05) within 1 week, while plasma osmolality remained unaltered at 284 +/- 3 mOsmol/l. Plasma vasopressin (0.45 +/- 0.1 pg/ml) was increased after 3 days (0.68 +/- 0.5 pg/ml) and rose further to 1.53 +/- 0.27 pg/ml after 1 week (P less than 0.05). Changes in plasma vasopressin concentration were not correlated with alterations in blood pressure. Our results show an increase in plasma vasopressin in the early phase of mineralocorticoid induced hypertension in man. However, the observed increase is moderate and does not seem to explain the increase in blood pressure alone, but could contribute to the blood pressure increase during mineralocorticoid treatment. PMID- 3327928 TI - Endothelium and responsiveness of vascular smooth muscle. AB - The endothelium of a wide variety of arteries can release a potent vasodilator substance (endothelium-derived relaxing factor). The relaxation of smooth muscle cells evoked by endothelium-derived relaxing factor is associated with activation of guanylate cyclase. Under certain conditions the endothelium can produce contracting factors as well. Dysfunction of the endothelium may lead to abnormal behaviour of the underlying smooth muscle, e.g. vasospasm. PMID- 3327929 TI - Diet and hypertension: critical concepts and controversies. AB - Diet, alcohol consumption and physical activity stand out as the major influences on blood pressure levels and hypertension. Many studies on the effects of different nutrients on blood pressure have been confounded by methodological problems, but a careful appraisal of these problems leads to new concepts in interpreting the literature, and allows some interesting conclusions to be drawn. PMID- 3327930 TI - Haemodynamic (systemic and renal) and humoral interactions between nicardipine and domperidone in hypertensives. AB - We studied the haemodynamic (systemic and renal) and humoral effects of nicardipine, a dihydropyridine calcium entry blocker in essential hypertensives and whether DA2 dopaminergic receptor blockade, induced by domperidone, might modify these effects. Eight uncomplicated mild to moderate hypertensives received placebo (saline) for 30 min followed by i.v. nicardipine (0.06 mg/min) for 30 min and repeated the same sequence introducing domperidone (10 mg i.v.) between saline and nicardipine; the effects of each treatment were followed for 30 min. The sequence was randomized with a 72-h interval between each study. Compared with placebo, nicardipine significantly reduced mean blood pressure (-14%) and renovascular resistance (-28%), increased heart rate (+15%), renal plasma flow (RPF; +21%), glomerular filtration rate (GFR; +43%) and urinary sodium excretion (+181%). The acute natriuretic effect of nicardipine was associated with an increase in the amount of filtered sodium (+43%) and with fractional sodium excretion (+110%), and a direct correlation was found between changes in RPF and in urinary sodium excretion (r = 0.68) and fractional sodium excretion (r = 0.57). Plasma renin activity (PRA) did not change, plasma aldosterone was significantly reduced (-10%) and plasma noradrenaline significantly increased (+63%). Domperidone pretreatment prevented the GFR increase induced by nicardipine and increased the noradrenaline response (+107%), but did not change the other actions of nicardipine. These data show that nicardipine, when acutely infused in essential hypertensives, while reducing blood pressure and reflexly activating the sympathetic nervous system, significantly increases urinary sodium excretion, RPF and GFR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3327931 TI - Antihypertensive efficacy and tolerability of captopril in the elderly: comparison with hydrochlorothiazide and placebo in a multicentre, double-blind study. AB - In this study we compared the antihypertensive efficacy and tolerability of captopril at 25 mg twice daily, hydrochlorothiazide (HCTZ), 12.5 mg twice daily and placebo in a multicentre, double-blind, randomized study that included 152 essential hypertensive patients (77 males, 75 females, 87 WHO stage I, 65 WHO stage II, aged 69 +/- 4 years, mean +/- s.d.). Supine and standing blood pressure were similarly reduced by captopril and HCTZ (P less than 0.01 for both compared with placebo). The heart rate did not change. Captopril (25-30 mg twice daily) and HCTZ (12.5 mg twice daily), alone or in combination, maintained their antihypertensive effect during a 24-week single-blind follow-up study. During the follow-up, diastolic blood pressure remained less than 100 mmHg in seven essential hypertensives on placebo, in 45 on captopril and in 25 on HCTZ. Side effects were observed in seven essential hypertensives during placebo (treatment withdrawn in two), in eight during HCTZ and in three during captopril. Serum potassium was reduced (P less than 0.05) and uric acid was increased (P less than 0.01) only during HCTZ. We conclude that captopril and HCTZ have similar antihypertensive efficacy in the elderly; however, captopril appears to be better tolerated. PMID- 3327932 TI - Problems in the treatment of hypertension. AB - The major problems discussed and the responses are: (1) Is blood pressure measurement by ordinary sphygmomanometer still valid as a guide to decisions? Yes. (2) Is translation of population into individual risk based on blood pressure alone appropriate as the sole criterion for treatment? No. All risk factors and observation time are important. (3) Does a good response to medical treatment preclude full investigation? No. Knowledge is better than ignorance. (4) Are trial results useful clinically? Yes, if selection of subjects, major risk factors, and relative benefits of treatment are clearly presented. (5) Do some drugs have beneficial effects on stroke and myocardial infarct other than purely those due to lowering of pressure? Yes: bendrofluazide and stroke. (6) Can smoking interfere with beneficial effects? Yes: propranolol and stroke. (7) Have some drugs serious adverse effects? Possibly thiazide in myocardial ischaemia. (8) Is it dangerous to lower the diastolic pressure below 90 mmHg? Possibly. (9) Is there a hypertension treatment paradox in stroke and myocardial infarct? Yes. PMID- 3327933 TI - Pulpal responses after the avulsion and replantation of permanent teeth. PMID- 3327934 TI - Macroglossia of the past: surgery and orthopedics. PMID- 3327935 TI - Clinical evaluation of glass cementation on stainless steel crown retention. PMID- 3327936 TI - Development and application of weighted criteria to assess stainless steel crown restorations on primary teeth. PMID- 3327937 TI - Primary anterior strip crowns: a new technique for severely decayed anterior primary teeth. PMID- 3327938 TI - New approaches to hormonal acceleration of fetal lung maturation. AB - The paper reviews the effects on lung maturation of glucocorticoids in animals and humans and presents relevant recent findings from the author's laboratory. It is now well established that antenatal glucocorticoid treatment reduces the incidence and severity of the respiratory distress syndrome (RDS) in prematurely born infants. The recommended doses of glucocorticoids produce fetal glucocorticoid activity levels similar to those of newborns with RDS or prolonged rupture of the membranes. Extensive follow-up studies have shown that adverse effects on child development are unlikely to occur. It is also evident that a significant number of fetuses do not respond to the treatment, which is of particular consequence in fetuses of less than 28 weeks gestation. These fetuses are less likely to respond to glucocorticoid therapy that fetuses between 28 and 32 weeks gestation and are at a higher risk of developing complications due to their immaturity. In fetal sheep, there is a similar decrease in the efficacy of glucocorticoids on lung maturation with decreasing gestational age. Simultaneous infusion of cortisol, triiodothyronine and prolactin but not of any of these hormones administered singly or in combination of two produced mature lungs in fetal sheep of 125 days gestation. Similar results were obtained with thyrotropin releasing hormone (TRH) and cortisol. It remains to be seen whether the combined administration of glucocorticoids and TRH accelerates lung maturation in human fetuses. PMID- 3327939 TI - Surfactant substitution in the newborn by application of artificial surfactant. AB - A protein-free artificial surfactant (ALEC) composed of two phospholipids when given as a prophylactic treatment at birth to very premature babies in randomized controlled trials. It was shown to reduce the severity of RDS, the ventilator pressure, the inspired oxygen requirements, the compliance of the respiratory system, the neonatal mortality and the incidence of ventricular hemorrhage. There are no apparent side effects from this treatment. PMID- 3327940 TI - [Clinical drug information system]. PMID- 3327941 TI - [Study on insulin-like efficacy and insulin release activity of meat, fishes and shellfish in vitro. I]. PMID- 3327942 TI - [Use of fermenter dialysis culture technic to grow clinically important bacteria which carry capsules. I. Escherichia coli K1]. AB - For mass culture of Escherichia coli K1 a fermenter dialysis culture technique based on an artificial hollowfiber kidney and substrate feeding is described and compared with conventional shaking culture and fermenter batch culture techniques. Important growth parameters as bacterial dry weight, optical density and live cell counts demonstrate the advantage of this new method. On the basis of bacterial yields, effectivity had increased about 100 fold. The synthesis of K1 capsular polysaccharides, which is influenced by a number of factors, proved to be good. Thus it was possible to obtain the quantities of native capsular substance necessary for bed-side diagnostics and the investigation of this virulence marker. PMID- 3327943 TI - Nutritional management of infants on continuous peritoneal dialysis. PMID- 3327944 TI - Rat jejunal disaccharidase activity increases biphasically during early post natal development. AB - 1. Injection of hydrocortisone into 9-day-old rats induces the early appearance of sucrase in jejunal homogenates, the time course of the subsequent increase and magnitude of the final effect being similar to that seen to start on day 16 during normal development. 2. Cytochemical comparison of the effect of hydrocortisone and normal development on the appearance of a mixture of sucrase, maltase, isomaltase and trehalase disaccharidases (alpha-glucosidase activity) shows this enzyme to appear first in enterocytes at the base of the villus. Enzyme activity then increases and spreads along the whole villus during the next 96 h. 3. The rate at which enterocytes migrate along the villus after hydrocortisone injection is not significantly different from that measured during the early phase of normal development. The later phase of normal development is associated with a threefold increase in cell migration rate and a twofold increase in crypt depth. 4. The rate at which alpha-glucosidase activity increases in enterocytes at the base of the villus during early normal development is similar to that determined after hydrocortisone injection into younger animals. This rate of appearance increases eight to tenfold during normal development, shortly after the appearance of solid food in the stomach of normal control animals. 5. Injection of steroid hormones into young rats is generally supposed to mimic events taking place normally at weaning. Present results show alpha-glucosidase induction during normal development to be under more complicated control than had been previously suspected. PMID- 3327945 TI - Protein kinase C activators inhibit the inositol trisphosphate-mediated muscarinic current responses in rat lacrimal cells. AB - 1. Pre-incubation (1-5 min) with 12-O-tetradecanoylphorbol-13-acetate (TPA, 8-16 nM), a tumour-promoting phorbol ester known to activate protein kinase C, was found to inhibit acetylcholine-induced Ca2+-dependent K+ and Cl- currents in cells isolated from rat lacrimal glands. 2. Previous work showed that the same currents may be elicited by dialysing cells with a high-Ca2+ (1.0 microM) solution, with inositol trisphosphate (InsP3), or with guanosine 5'-[gamma thio]triphosphate (GTP-gamma-S). 3. After TPA incubation both types of currents could be elicited by dialysis with elevated Ca2+ solutions, although the magnitude of the K+ current was slightly reduced in comparison with control cells. 4. Responses to intracellular dialysis with InsP3 (20 microM) were similar to those in untreated cells, indicating that the Ca2+ release process was unaffected. 5. However, the response to GTP-gamma-S (0.2-0.5 mM) dialysis was strongly inhibited in TPA-treated cells. 6. These results suggest that protein kinase C exerts an inhibitory action on the pathway leading from receptor activation to inositol trisphosphate production. PMID- 3327946 TI - 4-Methyl-pyrazole. Monograph. PMID- 3327947 TI - [Reservoirs of resistance plasmids]. PMID- 3327948 TI - DNA methylation, gene expression and chemical carcinogenesis. PMID- 3327949 TI - Porcine cardiac valvular subendothelial cells in culture: cell isolation and growth characteristics. AB - We established culture lines derived from the subendothelial region of the porcine aortic valve. These cells were isolated by extensive collagenase digestion of valvular tissue and were serially propagated with stable morphology. In sparse culture, valve subendothelial cells resembled skin fibroblasts. When confluent, the valve subendothelial cells formed ridges and piles similar to vascular smooth muscle cells. Endogenous in vitro labeling experiments using 35S methionine showed that valve subendothelial cells synthesized and released several proteins not observed in parallel experiments using porcine skin fibroblasts and smooth muscle cells. Mitogen assays using media conditioned by porcine aortic valvular endothelial cells showed that the valve subendothelial cells, when compared to skin fibroblasts and smooth muscle cells, were particularly avid responders to the growth factors released by valve endothelial cells in vitro. The valve subendothelial cells also released 10-fold more prostacyclin in response to arachidonate than did skin fibroblasts or smooth muscle cells. We conclude that valve subendothelial cells show features that distinguish them from other cultured mesenchymal cells, and that this culture system will be useful for studies of the cellular basis of valvular heart disease. PMID- 3327950 TI - Antibody titer to group A streptococcal polysaccharide in rheumatic fever and rheumatic heart disease. AB - Antibody to group A streptococcal polysaccharide (ASP) is the only antibody of cellular components which is now detectable in clinical practice. Streptococcal polysaccharide is known to have cross-immunity with the glycoprotein of human heart tissue, and has been discussed as a pathogenesis of rheumatic carditis and valvular heart disease. In this study, ASP titer was determined by passive hemagglutination technique in patients with rheumatic fever and rheumatic heart disease. ASP titer showed higher levels in these patients compared to control children, but there was no specificity in rheumatic carditis or rheumatic heart disease. PMID- 3327951 TI - Anti-streptopolysaccharide antibody in children with rheumatic fever and scarlet fever. AB - As the serological test of streptococcal infection, the measurement of anti exotoxin antibodies such as ASO is widely practiced. M protein of the cell wall of group A streptococcus has type specificity. To detect the anti M protein antibody is very significant, but it is not easy to apply this to clinical practice because there are many types and because of the difficulty of purifying M protein. C polypeptide has group specificity, so the measurement of the antibody to C polypeptide is very important as the serological test of group A streptococcus. PMID- 3327952 TI - Study of antibody response to 4 streptococcal antigens in rheumatic fever and Kawasaki disease with or without cardiovascular lesions. AB - Patients with rheumatic fever (RF) and Kawasaki disease (MCLS) were divided into two groups, one with and the other without cardiovascular lesions, and their sera were examined for antibodies to 4 streptococcal antigens: anti-streptococcal polysaccharide (ASP), anti-deoxyribonuclease B (ADN-B), anti-streptolysin O (ASO) and anti-streptokinase (ASK) in order to clarify the relationship between group A streptococci and these two diseases. In RF the frequency of positive levels of ASP at its early stage was lower than those of the other 3 antibodies, but the ASP titer tended to persist at elevated levels. The frequency of ADN-B in patients with rheumatic heart disease (RHD) was higher than that in those without RHD, but with regard to the other antibodies no difference was found between the two. Of the 4 antibodies the frequency of at least one positive level was 100% in all the sera of RF patients within 3 months from onset. The differences in the frequencies of positive levels of all 4 antibodies in both MCLS and the controls did not prove to be significant. The frequencies of ASP, ADN-B and ASO in the sera of patients without cardiovascular lesions tended to be slightly higher than those in patients with cardiovascular lesions. PMID- 3327954 TI - [History of modern anesthesiology: from a neuropathologist's point of view]. PMID- 3327953 TI - Coronary arteritis in mice after systemic injection of bacterial cell wall peptidoglycan. AB - We examined cell wall peptidoglycan (PGL) derived from group A streptococcus and other bacteria for possible induction of coronary arteritis in mouse strains. The histological finding of the main trunk of the coronary arteries of BALB/c, DBA/1J, C57BL/6 and DBA/2 mice, which were given an intravenous injection of sonicated PGL fragments of st. pyogenes at 500 micrograms per mouse 4 times at intervals of 1 week, showed diffuse cellular infiltration in the vascular wall as well as perivascular space. Marked hyperplasia of the endothelial cells was noted and necrosis of the medial smooth muscle of the coronary artery also was observed. The elastica stain clearly demonstrated fragmentation and degeneration of the elastic fibers. The histological change of the originating site of the aorta also noted swelling or hyperplasia of the endothelial cells and perivascular cellular infiltration. PGL fragments of st. mutans, st. sanguis and s. aureus did not cause any heart lesions. Coronary arteritis induced by st. pyogenes PGL could be very useful as an experimental animal model of Kawasaki's disease. PMID- 3327955 TI - [Clinical evaluation of isoflurane--a multicenter clinical trial]. PMID- 3327956 TI - [Clinical evaluation of isoflurane vs enflurane--a multicenter well-controlled study]. PMID- 3327957 TI - [Nitrous oxide increases cerebral artery flow velocity and cerebrospinal fluid pressure in man]. PMID- 3327959 TI - [Anesthesia and theophylline]. PMID- 3327958 TI - [Endocrine stress response during spinal and epidural anesthesia for cesarean section]. PMID- 3327960 TI - [History of spinal anesthesia in Japan (2). 1901-1907]. PMID- 3327961 TI - [New antimicrobial agent series XXV: imipenem/cilastatin sodium]. PMID- 3327962 TI - [New antimicrobial agent series XXVI: cefteram pivoxil]. PMID- 3327963 TI - [Clinical trials on cefuzonam in obstetrics and gynecological infections]. AB - Ten patients (3 cases of abscess of vaginal cuff, 1 case of abscess of vaginal cuff complicated with parametritis, 2 cases of pyosalpinx, 1 case each of abscess of abdominal wall, pelvic cellulitis, pyometra with cervical cancer and paraovarian abscess were treated with cefuzonam (CZON), which was administrated by intravenous drip infusion at a dose of 1,000 mg twice a day for 3 to 10 days (6 g to 19 g total). The clinical effectiveness reached 70.0% including 1 excellent case, 6 good cases and 3 poor cases. Bacteria were detected in all the 10 cases, and with CZON treatment, bacterial eradication were obtained in 3 cases, bacteria decreased in 3 cases, no change in 2 cases and bacterial replacement occurred in 2 cases. No abnormal laboratory findings and side effects were noted. From the above results, CZON seemed to be a highly effective and useful agent for gynecological infections. PMID- 3327965 TI - [The antimicrobial activity of sisomicin against fresh clinical isolates]. AB - Antimicrobial activities of sisomicin (SISO) against clinical isolates obtained in the second half of 1986 were investigated together with other 4 aminoglycosides (AGs) (gentamicin (GM), tobramycin (TOB), dibekacin (DKB), amikacin (AMK] and 2 cephems (cefotiam, cefotaxime), and were compared to the results reported in the period of late 1970's through early 1980's in Japan. 1. The incidence of SISO-resistant Staphylococcus aureus in the present study was 18% and is comparable to that of the other studies suggesting that the incidence of SISO resistant strains remains on the stable level. The incidence of SISO resistant Pseudomonas aeruginosa showed the tendency of slight increase. 2. SISO resistant strains of Enterobacter spp., Serratia marcescens and Citrobacter freundii did not show increase from the 1970/1980 levels. 3. Isolation rates of SISO-resistant indole(+) Proteus varied depending on strains. Isolation rates of SISO-resistant P. vulgaris and Morganella morganii were both as low as 4%, but that of Providencia rettgeri was as high as 60%. Refering to an American study reporting that the Genus Providencia including P. rettgeri showed high incidence of resistance to SISO as well as to GM or TOB, we pointed out that the antimicrobial activity of AGs against Genus Providencia should be evaluated separately from those of other indole(+) Proteus strains. 4. No SISO-resistant strains of Escherichia coli, Klebsiella pneumoniae or P. mirabilis were found. 5. SISO had good antimicrobial activity against most of the investigated species and SISO may still be regarded as one of the clinically useful AGs. PMID- 3327964 TI - [Laboratory and clinical studies of flomoxef]. AB - Laboratory and clinical studies were performed on a new oxacephem antibiotic, flomoxef (FMOX, 6315-S). In vitro antibacterial activity of FMOX was evaluated in comparison to latamoxef (LMOX), cefmetazole (CMZ), cefazolin (CEZ) using clinically isolated strains of Gram-negative and Gram-positive bacteria. Antibacterial activities of FMOX were stronger than LMOX, CMZ, CEZ against Escherichia coli, Klebsiella but only slightly effective against Staphylococcus aureus. This antibiotic drug was administered to 5 patients consisting of 2 cases with pneumonia, one each with pyelonephritis, chronic bronchitis and urinary tract infection. The drug was given in 1 g drip infusion twice a day for 8 to 13 days. Clinical efficacies of FMOX were excellent in 1 case, good in 2, fair in 1, and unevaluable in 1. As for bacteriological effect of FMOX, organisms were eradicated in 3 cases. No side effect was noted and there was no abnormal change in laboratory findings. PMID- 3327966 TI - [Clinical laboratory approach for estimating the effective administrative dose of latamoxef. Significance of a 4-category system interpretation of the latamoxef disc susceptibility test]. AB - In vitro activities of latamoxef (LMOX) against 249 clinical isolates were determined using the agar dilution method at an inoculum level of 10(6) CFU/ml. LMOX was highly active against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis (except 2 out of 30 strains) and Proteus vulgaris with MIC values below 3.13 micrograms/ml. It was also active against Enterobacter aerogenes with MIC80 of 1.56 micrograms/ml. LMOX was less active against Serratia marcescens, inhibiting about 43% of strains at a level of 6.25 micrograms/ml. It was also less active against Staphylococcus aureus and Staphylococcus epidermidis, showing MIC80 of 12.5 and 50 micrograms/ml, respectively. LMOX was not active against Enterococcus faecalis and Pseudomonas aeruginosa. The reliability of the LMOX disc diffusion susceptibility test for quantitative estimation of antimicrobial activities was also investigated using 8 mm diameter discs (Showa) and 6 mm diameter discs (Difco), both of which contained 30 micrograms/disc of LMOX. These disc susceptibility test results were well correlated with MICs, hence the LMOX disc susceptibility test should be useful for the estimation of proper dose levels of LMOX. For the interpretation of LMOX disc test results, if uniform break points of zone diameters were used to test all bacteria, inhibitory zone diameters of Showa discs used on Staphylococcus were relatively large compared to MICs determined, probably due to decarboxylation of LMOX sodium salt in the discs. However, those of Difco discs were not, because Difco discs use LMOX ammonium salt. Both discs also showed relatively large inhibitory zone diameters compared to MICs determined against P. aeruginosa. Using different break points from those used for other bacteria to interpret inhibition zones for Staphylococcus and P. aeruginosa, these disc susceptivility tests should be useful to estimate approximate MICs. A 3 category system for the interpretation of disc test results has been used in USA and Europe, but a 4 category system is generally used in Japan. The 3 category system uses break points to classify bacteria into 3 categories of susceptibility according to MIC values as follows: Resistant (R) MIC greater than or equal to 64 micrograms/ml, intermediate (I) MIC 16-32 micrograms/ml, and susceptible (S) MIC less than or equal to 8 micrograms/ml. The 4 category system uses break points as follows: MIC less than or equal to 3 micrograms/ml, MIC greater than 3-15 micrograms/ml, (+) MIC greater than 15-60 micrograms/ml, (-) MIC greater than 60 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3327967 TI - [The compromised host]. PMID- 3327968 TI - The effects of isosorbide dinitrate on exercise-induced ST-segment elevation at the infarcted area in old myocardial infarction. AB - To clarify the clinical significance and therapeutic implication of exercise induced ST elevation at the infarcted area in old myocardial infarction (OMI), 30 patients with exercise-induced ST elevation underwent treadmill exercise testing. The patients with transient perfusion defects at the infarcted area on thallium 201 stress myocardial scintigraphy (group I: n = 12) revealed a decreased rate of ST elevation expressed as delta ST/delta HR X 10(2) after 10 mg of isosorbide dinitrate (ISDN), compared to the results of treadmill exercise testing under no medication (3.1 +/- 2.5 vs. 4.7 +/- 2.6, p less than 0.001). Exercise capacity and anginal threshold were improved after ISDN in group I. In contrast, the patients without transient perfusion defects (group II: n = 18) revealed an increased rate of ST elevation after ISDN (2.4 +/- 1.1 vs. 2.0 +/- 0.8, p less than 0.05). It is concluded from the above results that if exercise-induced ST elevation at the infarcted area reflects transient myocardial ischemia, ISDN can decrease it by its anti-anginal effect. Additionally, treadmill exercise testing with ISDN is a useful means of clarifying the underlying pathophysiology and management in OMI cases with this effect on exercise-induced ST elevation at the infarcted area. PMID- 3327969 TI - [Diagnostic imaging of endocrine diseases. Thyroid tumors]. PMID- 3327970 TI - [Diagnostic imaging of endocrine diseases. Parathyroid glands]. PMID- 3327971 TI - [Diagnostic imaging of endocrine diseases. Pheochromocytoma]. PMID- 3327972 TI - [Gene and molecular structure of cytochrome p-450]. PMID- 3327973 TI - [Structure of steroid receptors and functional analysis]. PMID- 3327974 TI - [Application of immunologic methods to the rapid diagnosis of bacterial infections]. PMID- 3327975 TI - [Reactivities of sera with enzyme immunoassay kits for human immunodeficiency virus antibody]. PMID- 3327977 TI - [Advance of human chromosome examination and its clinical application]. PMID- 3327976 TI - [Fundamental studies and reference values of cancer associated antigen NCC-ST 439]. PMID- 3327978 TI - [The ability of MRI under non-breathing to depict the hepatic veins and portal veins]. PMID- 3327979 TI - [A case of the megacystis-microcolon-intestinal hypoperistalsis syndrome]. PMID- 3327980 TI - [Studies on superoxide dismutase in the human skin. (5). Changes in the SOD induced by aging]. PMID- 3327981 TI - [Isolation and characterization of extracellular proteinases from Sporothrix schenckii]. PMID- 3327982 TI - Medicolegal identification of seminal fluid by the radioimmunoassay of prostatic acid phosphatase. PMID- 3327984 TI - [Changes in midwifery practice. Conclusion. Lessons in the history of midwifery]. PMID- 3327983 TI - [The detection test for spot of seminal fluid using anti-gamma-seminoprotein serum and anti-beta-microseminoprotein serum--forensic immunological studies of body fluids and secretion, report XXXI]. PMID- 3327985 TI - [History of nursing in Japan. 5. Medical care and nursing in the medieval age]. PMID- 3327986 TI - [Preoperative stage diagnosis by ultrasonography and evaluation of the echo pattern of renal cell carcinoma]. PMID- 3327987 TI - [Clinical study of 513 kidney transplantations]. PMID- 3327988 TI - [Diagnosis on bladder invasion of uterine cervical carcinoma by using transurethral radial scan ultrasound echotomography]. PMID- 3327990 TI - [A case of primary adenocarcinoma of renal pelvis]. PMID- 3327989 TI - [Localization of lumbosacral spinal neurons innervating the external urethral and anal sphincters]. PMID- 3327991 TI - Pre and post operative management of a child with burns. PMID- 3327992 TI - [Mechanisms of development of cardiac glycoside poisoning and its drug prevention in circulatory failure]. PMID- 3327993 TI - [Modern approach to the study of cardiohemodynamics of the right ventricle in myocardial diseases]. PMID- 3327994 TI - [Variants of chronic heart failure in ischemic heart disease patients and optimization of their treatment]. AB - Computer-assisted classification of hemodynamic data was performed in 172 patients with coronary heart disease aggravated by chronic heart failure. Six groups of patients have been identified, and an individual treatment algorithm has been proposed for each of those. The use of optimum individual treatment schedules has produced good or satisfactory clinical effect in 87.3%. PMID- 3327997 TI - [Achievements of surgical endocrinology in the Ukraine]. PMID- 3327995 TI - [Effect of anaprilin on the clinical course of stenocardia and the carbohydrate metabolic indices of ischemic heart disease patients in relation to the nature of their glucose tolerance]. AB - Fourteen-day anaprilin treatment of coronary patients with varying glucose tolerance has demonstrated that the drug's therapeutic efficiency was greater in patients with normal glucose tolerance. Anaprilin caused a moderate drop in baseline glucose level and considerably limited the degree of hyperglycemia in response to the glucose tolerance test in coronary patients with abnormally low glucose tolerance. Insulin content was virtually unaffected by the drug, irrespective of the type of glucose tolerance. PMID- 3327996 TI - [Status and prospects of the development of emergency surgical services in the Ukraine]. PMID- 3327998 TI - [Brief outline of the development of cardiological surgery in the Ukraine]. PMID- 3328000 TI - [A method of pancreatectomy in destructive pancreatitis]. PMID- 3327999 TI - [Duodenal obstruction as a complication of pancreatitis]. PMID- 3328001 TI - [A method of hermetization of pancreatojejunoanastomosis]. PMID- 3328002 TI - [Tubular gastrectomy with formation of an rectangular oblique gastrojejunal anastomosis]. PMID- 3328003 TI - [Comparative morphofunctional evaluation of ligation methods for hemostasis in resection of the kidney]. PMID- 3328004 TI - [A method for forming a biliodigestive anastomosis]. PMID- 3328005 TI - [Hemostatic therapy in bloodless methods of correcting hemophilic arthropathy]. PMID- 3328006 TI - [Ultrasonic echo location in the diagnosis of recurrent forms of goiter]. PMID- 3328007 TI - [The use of computerized static perimetry in patients with glaucoma]. PMID- 3328008 TI - [The contribution of D.D. Pletnev to the description of masked depression]. PMID- 3328009 TI - [Zinovii Moiseevich Volynskii (on the 90th anniversary of his birth)]. PMID- 3328010 TI - [Vitol'd Martselievich Novodvorskii (on the centenary of his birth)]. PMID- 3328011 TI - [Intersystemic clinical relations in gastroenterologic diseases]. PMID- 3328012 TI - [Exercise-induced asthma and calcium ion antagonists]. PMID- 3328013 TI - [Effect of calcitrin on the course of chronic obstructive bronchitis]. PMID- 3328014 TI - [Pulmonary tuberculosis in adults in the Soviet Union over the past 70 years]. PMID- 3328015 TI - Subcutaneous fat measurements of the leg using three protocols. PMID- 3328016 TI - An objective method for measurement of musculo-skeletal size in children and youth. PMID- 3328017 TI - Exercise, aging and fine motor performance: an assessment. PMID- 3328018 TI - A comprehensive model of the crypts of the small intestine of the mouse provides insight into the mechanisms of cell migration and the proliferation hierarchy. AB - A comprehensive model has been formulated for the proliferative behaviour of the crypts of the small intestine based on individual cell to cell relationships rather than on the average effects of all cells. The model accommodates a wide range of cell kinetic data and provides an insight into the mechanisms involved in cell movement within the columnar sheet of cells and into the relationship between the stem cells and their progeny. The model permits the number of stem cells and transit generations to be estimated. The number of stem cells is predicted to be not less than 4 and not more than 16 per crypt with cell cycle times of between 12 and 32 h respectively. Certain conclusions can be drawn concerning the mechanisms involved in the initial cell displacements after cell division. The model also allows an estimation of parameters which cannot be measured directly such as the degree of cell generation disorder and the amount of dispersion of cells within a cell lineage. PMID- 3328019 TI - Critical amino acids of p21 protein are located within beta-turns: further evaluation. AB - It has been shown that malignant activation of ras proto-oncogenes was mediated by point mutations which resulted in the single amino acid conversions at positions 12, 13 or 61 of the ras gene products (p21 proteins). By analyzing randomly mutated ras genes, it has been demonstrated that amino acid substitutions at residues 12, 13, 59 and 63 activated p21. Furthermore, it has been shown that residues 16, 116 and 119 in p21 played critical roles in the guanine nucleotide binding and, consequently, the ability of the protein to induce changes characteristic of cellular transformation. By using the protein conformational prediction method of Chou and Fasman, the present work predicts that these critical amino acids, except glutamic acid at position 63, are located within beta-turns. The major "hot spots" for ras activation are codons 12 and 61. The author has predicted in an earlier paper that the single amino acid conversions at positions 12 and 61 would occur at beta-turn conformation consisting of residues 10-13 and 58-61, respectively. In the present study, probabilities of beta-turn occurrence at residues 10-13 or 58-61 of the p21 proteins encoded by various ras genes are compared. The probability for the normal p21 containing glycine as residue 12 is greatest, and the cancer associated variants show less probabilities. The single amino acid substitutions at position 61 do not cause so decreased probabilities of beta-turn potential at residues 58-61, except the replacement by histidine. Histidine at position 61 is not predicted as occurring within a beta-turn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3328020 TI - The story of the Apricot Grove. PMID- 3328021 TI - A pioneer in establishing the tradition of keeping case records. PMID- 3328022 TI - Classics on dietotherapy. PMID- 3328023 TI - Contrasting patterns of lymphatic and blood circulatory disorders. PMID- 3328024 TI - Differences in lymphatic and blood capillary permeability: ultrastructural functional correlations. AB - The major structural features of lymphatic capillaries, as they contrast with blood capillaries and as they pertain to endothelial permeability, are reviewed briefly with special emphasis on intrarenal vessels. The most characteristic structural feature of lymphatic endothelium is the discontinuity of the basal lamina. Basal laminae of blood vessels, such as renal glomerular capillaries, are prominent and are known to play a role in preventing extravasation of plasma proteins. By analogy, the lack of a basal lamina around lymphatic capillaries can be considered to be of major functional importance in facilitating access of interstitial macromolecules to the abluminal surface of endothelial cells and thus to the transport pathways that provide entry to the lymph. Tracer studies with horseradish peroxidase, for example, reveal that the protein enters the intraendothelial cytoplasmic vesicular system suggesting that this system may provide a transport pathway. Tracer is also seen between adjacent endothelial cells but in the kidney, liver and thyroid these intercellular channels comprise relatively narrow spaces of about 20 nanometers or less and do not form prominent gaps such as are seen in lymphatics of the diaphragm and skin. Evidence that macromolecular transport across endothelial cells may be asymmetric, favoring movement from interstitium to lymph, is derived from 1) studies using isolated perfused lymphatics, 2) differential luminal and abluminal membrane staining with cationic stains, 3) the presence of charged microdomains on lymphatic endothelial cell surfaces revealed with macromolecules of different charges, and 4) studies on cultured monolayers of porcine arterial endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3328025 TI - Comparison of viscoelastic properties of walls and functional characteristics of valves in lymphatic and venous vessels. AB - The principal function of the lymphatic and venous system is to maintain a favorable environment for cells of the body. As a consequence mainly of hydrostatic forces, shifts of fluid usually occur between the vascular system and the extracellular space. To compensate for these shifts the veins are capable of active and passive changes in capacity that serve to modulate the filling pressure of the heart by adjusting the central blood volume. In addition to the venous function, the lymphatic function also contributes to compensate for the fluid shifts by drainage from the interstitial space. Namely, the general function of the lymphatic system is to return fluid and protein which escapes from the blood capillaries to the lymph circulation. To elucidate the mode of venous and lymph transport, therefore, it is of essential importance to obtain basic knowledge of the mechanical characteristics of the walls of the vessels and the functional characteristics of the lymphatic and venous valves dividing two adjacent compartments. In this communication, in order to answer the question, "Are Lymphatics Different From Blood Vessels?", I would like to review a comparison of viscoelastic properties of walls and functional characteristics of valves in lymph and venous vessels by use of our original data obtained with isolated canine veins and thoracic ducts and with isolated bovine mesenteric lymphatics (1-9). PMID- 3328027 TI - Experimental studies on the role of alkyl lysophospholipids in autologous bone marrow transplantation. AB - The selective cytocidal effect of alkyl lysophospholipids against neoplastic cells while sparing normal cells make these ideal candidates for purging leukemic cells from bone marrows obtained during remission. To test the feasibility of such an approach, a murine model and an in vitro human cell model were developed. In the murine system a mixture of normal bone marrow cells and WEHI IIIB myelomonocytic leukemic cells was incubated with varying doses of 1-O-octadecyl-2 O-methyl-rac-glycero-3-phosphocholine (ET-Me) for 24 hr before being injected into tail veins of lethally irradiated Balb/c mice. At doses of 20 and 100 micrograms/ml, long-term survivors were noted. The additional steps of freezing and thawing following incubation resulted in significantly longer survival with doses of 10 to 50 micrograms/ml, but were toxic to marrow stem cells at 100 micrograms/ml. In the in vitro model, normal marrow progenitor cells and leukemic cells (the promyelocytic cell line HL60) were exposed to varying concentrations of ET-Me for 1 and 4 hr alone or mixed, and clonogenicity was assayed by colony formation in semisolid medium during 7-14 days' incubation. At doses up to 100 micrograms/ml exposed for 4 hr normal progenitor cells were spared and HL60 colonies eliminated. Other phospholipids analogues were less effective in eliminating leukemic cells, but spared normal progenitor cells. A survey of fresh leukemic cells found varying degrees of sensitivity to ET-Me, indicating the need for testing a variety of compounds. These studies clearly indicated the potential usefulness of alkyl lysophospholipid compounds in selectively purging leukemic cells from remission marrows for autologous bone marrow transplantation. PMID- 3328026 TI - Biosynthesis and biotransformation of ether lipids. AB - Some naturally occurring as well as synthetic ether lipids are biologically active. In certain cases, the effects of these substances are enhanced, in others, they are inhibited by compounds that were isolated from natural sources or prepared by chemical synthesis. The biotransformation of natural or "unnatural" ether lipids in microorganisms, plant or animal tissue also can lead to substances that elicit biological effects. The production of such compounds through various biotechnological techniques is a field wide open for future exploration. In addition to animal cell cultures, plant cell cultures may become useful tools in biomedical studies concerned with ether lipids. PMID- 3328028 TI - Phase I trial of the thioether phospholipid analogue BM 41.440 in cancer patients. AB - BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is a new thioether phospholipid, which has been shown to possess antineoplastic, antimetastatic, anti-invasive and immunomodulating properties in several tumor models. The mechanism whereby this compound exerts its direct antineoplastic effect is thought to be related to specific interference with the normal phospholipid metabolism, preferentially of neoplastic cells. BM 41.440 was evaluated in a multicenter phase I study in patients (pts) with refractory cancers. In phase I A, 34 pts were orally treated with doses ranging from 0.5 to 7.0 mg/kg body weight (bw). Three different formulations were tested. The maximum tolerated dose (MTD) was ca. 5 mg/kg bw. The limiting side effects were nausea and vomiting. There was no evidence for systemic toxicities like myelosuppression, nephro-, neuro-, hepatotoxicity or hematological side effects. The current phase I B is designed to determine the MTD of BM 41.440 administered orally on a daily schedule for at least eight weeks. So far, 19 pts have entered this trial at dose levels ranging from 1.0 to 5.0 mg/kg bw/day. Some pts receiving 1.0 and 2.5 mg/kg bw/day, respectively, have been treated, up to now, for more than nine months. Clinical progress was followed with at-least-weekly blood counts, chemistry profiles, urine analysis, liver function tests and recordings of side effects. Tumor parameters were evaluated at eight-week intervals. In parallel, pharmacokinetic investigations were performed in some pts in phase I A and IB. First results on tolerability and therapeutic efficacy of the long-term BM 41.440 treatment are reported in this intermediate evaluation. PMID- 3328029 TI - Clinical phase I pilot study of the alkyl lysophospholipid derivative ET-18-OCH3. AB - Sixteen patients suffering from widespread malignant disease, the majority pretreated and found in poor general health, were treated in a phase I pilot study with the alkyl lysophospholipid derivative 1-O-octadecyl-2-O-methyl-rac glycero-3-phosphocholine (ET-18-OCH3). Eleven patients were treated intravenously, and five were given oral therapy. Prolonged IV administration of 15-20 mg/kg/day at a concentration of 5 mg ET-18-OCH3 per 1 ml 20% human serum albumin could be continued safely. The maximum-tolerated dose was either 50 mg/kg as a single injection or 20 mg/kg during daily dispensions. Grade 2-4 toxicity, as pulmonary edema and impairment of hepatic function, then occurred during daily treatment. Toxicity was reversible. Mitogen stimulation and mixed lymphocyte culture studies revealed possible immunosuppressive effects of higher doses of ET 18-OCH3. There were no chromosomal changes in cytogenetic studies. Frequent post mortem examinations revealed no further toxicity. IV and oral treatment showed few encouraging response data since there were two partial remissions in non small cell lung cancers and a reduction of leukemic blasts to less than 10% in an acute myelomonocytic leukemia. PMID- 3328031 TI - [Alpha 1-antitrypsin phenotypes and their role in medical diagnosis]. AB - Alpha-1-antitrypsin is a glycoprotein of blood exhibiting the properties of a proteolytic enzymes inhibitor. It occurs in a number of polymorphic variants transmitted genetically, the differentiation of which enables to use electrophoretic methods. The authors surveys literature, involving also her own experience, on the diagnostic use of alpha-1-antitrypsin phenotypes. The variants related to alpha-1-AT deficiency are associated with an increased incidence of certain diseases: obstructive pulmonary disease, liver cirrhosis in children, cancer. An early establishment of alpha-1-antitrypsin phenotype may be significant for occupational prevention, furthermore, it may be helpful in the highlighting of etiology of certain liver diseases in early childhood. PMID- 3328032 TI - The effect of biotransformation of 2,4-dinitrotoluene on its mutagenic potential. AB - Because both oxidative and reductive metabolism of the hepatocarcinogen 2,4 dinitrotoluene (2,4-DNT) can occur in vivo, we have examined the mutagenicity of compounds which can be formed from 2,4-DNT in an attempt to establish which metabolic pathways contribute to the formation of genotoxic products. A quantitative reversion assay using Salmonella typhimurium TA98 was used to evaluate the mutagenicity of these compounds. 2,4-Dinitrobenzyl alcohol, 2-amino 4-nitrotoluene and 2-nitroso-4-nitrotoluene were found to be more mutagenic to S. typhimurium than is 2,4-DNT and did not require metabolic activation by post mitochondrial supernatants of Aroclor-induced rat liver homogenates (S9) for their effect. 2-Amino-4-nitrobenzoic acid was also mutagenic to S. typhimurium TA98 in the absence of S9, but its mutagenicity was enhanced when S9 was included in the incubation mixture. 2,4-Diaminotoluene required S9 for demonstration of mutagenicity and was approximately as effective, on a molar basis, as 2,4-DNT in inducing reversion to histidine prototrophy. These results suggest that both oxidative and reductive metabolism may be involved in production of mutagenic metabolites of 2,4-DNT. PMID- 3328030 TI - Ether lipids and analogs in experimental cancer therapy. A brief review of the Munich experience. AB - This review covers the work of our laboratory on the antineoplastic activity of some ether lipids and derivatives that are related to platelet-activating factor (PAF). Various 1-O-alkyl lysophospholipid derivatives (ALP) show therapeutic activity in mouse transplant tumor models and in metastatic 3-Lewis lung carcinoma in vivo. However, certain autochthonous mouse leukemias and radiation induced lymphomas are resistant to ALP treatment. The therapeutic effects of these compounds are partially due to the activation of cytotoxic macrophages and direct cytotoxicity. Approximately 20 ether lipids and derivatives were tested for direct cytotoxicity in cells from human solid tumors and leukemias using [3H]thymidine uptake, trypan blue dye exclusion, human tumor clonogenic assays (HTCA) and cell morphology as criteria. Certain ALP, thioether lysophospholipid derivatives (TLP), ether-linked lipoidal amines, sn-2 analogs of PAF, and conjugates of ether lipids and cytosine arabinoside were found cytotoxic in a dose- and time-dependent fashion. Cytotoxicity of some of the ether lipids tested is based on destruction of cell membranes. Structure-activity studies were performed to better understand the mechanisms leading to accumulation and cytotoxicity of ALP. Comparative studies with normal bone marrow cells and leukemic blasts from humans revealed preferential anti-leukemic cytotoxicity of three ether lipids. PMID- 3328033 TI - Assay of ptaquiloside, the carcinogenic principle of bracken, Pteridium aquilinum, by mutagenicity testing in Salmonella typhimurium. AB - The mutagenicity of ptaquiloside, the carcinogenic principle of Pteridium aquilinum, was tested in Salmonella typhimurium TA100 and TA98. Under weakly basic conditions (pH 8.5), ptaquiloside decomposed into a conjugated dienone (considered to be the ultimate form), which was mutagenic in both strains. A novel bioassay, using the pre-incubation method at pH 8.5 with S. typhimurium tester strains was developed for the assay of ptaquiloside extracted from plants. By this bioassay the ptaquiloside content of ferns collected at different localities during various seasons, and in various parts of the plant was determined. The ubiquitous presence of ptaquiloside in fresh plant materials was confirmed. Bracken processed in alkali was found not to contain the carcinogen. PMID- 3328035 TI - Study of the genotoxic potential of 17 mycotoxins with the SOS Chromotest. AB - Seventeen mycotoxins [aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1), G2 (AFG2), aflatoxicol, sterigmatocystin, patulin, citrinin, penicillic acid, T-2 toxin, diacetoxyscirpenol, zearalenone, zearalenol (alpha and beta isomers 1:1), ochratoxin A, norsolorinic acid, averufin, versicolorin A] were tested using the SOS Chromotest (PQ37 and PQ35). Six of the mycotoxins (AFB1, AFG1, AFB2, aflatoxicol, sterigmatocystin and versicolorin A) were genotoxic on PQ37 strain with and without metabolic activation. The results obtained with metabolic activation are in agreement with positive results obtained in other tests of genotoxicity. Except for AFB2, the presence of a double bond C8-C9 in the dihydrobenzofurane (DHBF) ring explained the activity due to the formation of an epoxide, but the coumarin cyclopentenone ring also plays a role in the qualitative differences of genotoxic activity. The wild-type uvrB gene in PQ35 decreases the genotoxic response with and without metabolic activation. Without metabolic activation, only mycotoxins possessing the DHBF ring group and double linkage C8-C9 exhibit a genotoxic effect. PMID- 3328034 TI - Sequential and differing nitroreductive pathways for mutagenic nitropyrenes in Salmonella typhimurium. AB - The nitro group of nitropyrenes is required for mutagenicity in Salmonella typhimurium. 1-Nitropyrene and 1,3-dinitropyrene are reduced by the 'classical' nitroreductase, which involves a single electron transfer, while the reduction of the first nitro group of 1,6- and 1,8-dinitropyrene proceeds by a two-electron transfer mechanism and involves a different enzyme. However, reduction of the second nitro group, which is not necessary for the mutagenicity of nitropyrenes but is required for the mutagenicity of aminonitropyrenes, is catalyzed by the 'classical' nitroreductase. PMID- 3328036 TI - Genotoxicity of two fecal steroids in murine colonic epithelium assessed by the sister chromatid exchange technique. AB - Two components of human feces are known to induce nuclear anomalies in mice when applied intrarectally, but to be nonmutagenic in Salmonella. We have tested these two compounds for their ability to induce sister chromatid exchanges in the colonic epithelium of mice, the same tissue in which they induce nuclear anomalies when administered by the same route. One, 4-cholesten-3-one, induced sister chromatid exchanges whereas the other, 5-alpha-cholestan-3-one did not, even at the maximum feasible dose. The results suggest that 4-cholesten-3-one is more likely to be a significant factor in human colon cancer than the 5-alpha analog. PMID- 3328037 TI - Chemical and physical agents assayed in tests for mitotic intergenic and intragenic recombination in Aspergillus nidulans diploid strains. AB - Data from Aspergillus nidulans mitotic recombination assays published over the period 1960-1986 are briefly reviewed. The results of the testing of 104 chemical agents and three physical agents are summarized. A tentative comparison of the performance of recombinational, mutational and aneuploidy assays in A. nidulans suggests that the former can effectively detect DNA-damaging agents which either induce true genetic recombination (intergenic or intragenic crossing-over) or mimic it by inducing chromosome structural damage which allows the expression of recessive genetic markers. On the other hand, aneuploidy tests proved to be sensitive both to chemicals directly affecting chromosome segregation (e.g. spindle poisons) and to the majority of DNA-reactive compounds assayed. PMID- 3328039 TI - Protection of Chinese hamster cells against the cytotoxic and mutagenic effects of alkylating agents by transfection of the Escherichia coli alkyltransferase gene and a truncated derivative. AB - The cytotoxic and mutagenic effects of various monofunctional and bifunctional alkylating agents have been assessed in V79 Chinese hamster cells that express either the entire O6-alkylguanine (O6AG) and alkylphosphotriester alkyltransferase (ATase) gene (clone 8 cells) or a truncated form that codes only for O6AG ATase activity (clone SB cells). Protection ratios, as determined by D37 values, were greater for clone 8 cells than for SB cells. Significant protection against the mutagenic effects of N-methyl-N-nitrosourea and ethylmethanesulphonate at the hypoxanthine phosphoribosyltransferase (HPRT) locus was observed in clone 8 and SB cells. Streptozotocin and the haloethyl nitrosoureas, chlorozotocin and bis-chloroethylnitrosourea were less efficient in inducing HPRT-deficient mutants and a smaller degree of protection was afforded by the transfected genes. This is possibly due to the propensity of these compounds to induce multi-locus deletions. Southern analysis of DNA from clone 8 and SB cells indicated the presence of multiple copies of the plasmid integrated into clone 8 cells but few copies in clone SB cells. The copy number did not change but ATase levels fell when cells were grown in the absence of G418. PMID- 3328038 TI - Genotoxicity of compounds from cooked beef in repair-deficient CHO cells versus Salmonella mutagenicity. AB - A series of compounds isolated on the basis of their mutagenicity in the Ames/Salmonella reversion assay were previously identified in fried beef and chemically synthesized for further evaluation. In this study three of these compounds were tested for genotoxic effects in the UV5 line of Chinese hamster ovary (CHO) cells, which is deficient in nucleotide excision repair. Both 2-amino 3,4-dimethyl-imidazo]4,5-f]quinoline (MeIQ) and 2-amino-3,8-dimethyl-imidazo[4,5 f]quinoxaline (MeIQx) gave very weak responses for cell killing, hprt mutation induction and sister chromatid exchange. These effects occurred at doses in the range of 100-800 micrograms/ml (approximately solubility limit), and dose dependent increases were not observed. Induction of chromosomal aberrations did not occur with either compound. Nor did either of these compounds produce differential cytotoxicity in normal CHO cells versus UV5 cells, indicating that potentially repairable DNA damage was not responsible for the observed cell killing. In contrast to these results, 2-amino-1-methyl-6-phenylimidazo [4,5 b]pyridine (PhIP), which constitutes greater than 90% of the mass of bacterial mutagens in beef, was strongly positive for all endpoints at doses in the range 1 3 micrograms/ml. PhIP also gave marked differential cytotoxicity (ratio of 6) and cell survival curves that were strongly dependent on repair capacity. Because PhIP is 50- to 300-fold less mutagenic than MeIQ and MeIQx in Salmonella TA1538, these results point to major differences between the bacterial and mammalian assays in terms of the relative potency of these food-related compounds. PMID- 3328040 TI - Sodium fluoride and chromosome damage (in vitro human lymphocyte and in vivo micronucleus assays). AB - The clastogenic potential of sodium fluoride was determined both in vitro (using cultured human lymphocytes) and in vivo (using the rat bone-marrow micronucleus test). The incidence of chromosome aberrations in human lymphocyte cultures exposed to 20 or 40 micrograms/ml sodium fluoride (3 and 9% respectively) was significantly increased compared with control cultures (0.5%). However, the incidence of micronucleated polychromatic erythrocytes in male AP rats dosed 1000 mg/kg NaF (the maximum tolerated dose over 24 h) or 500 mg/kg NaF was similar to that in the animals dosed distilled water (vehicle control). Thus, sodium fluoride is clastogenic in vitro but not in vivo. PMID- 3328041 TI - Proteinase production and pathogenicity of Candida albicans. I. Invasion into chorioallantoic membrane by C. albicans strains of different proteinase activity. AB - In order to investigate a role of proteinase in the pathogenesis of Candida infections, invasion of C. albicans strains of different proteinase activity into the chorioallantoic membrane (CAM) of developing chicks was studied. Eight strains were used after examining the inducible proteinase activity in the culture containing bovine serum albumin as the sole source of nitrogen. Six were proteinase-producing strains (type I) and two were proteinase-deficient ones (type II). Type I strains were subdivided into type Ia strains in which the proteinase activity persisted for a week in the in vitro culture and type Ib ones in which the enzyme activity was lost by the 7th day after inoculation. By inoculation onto CAM, the type I strains could invade the tissue in which secreted proteinase was detected on the periphery of the invading Candida cells by immunohistochemical method. At an early stage of the infection, proteinase secretion was detected on the surface of the yeast cells before their entry into the tissue. The type II strains remained on the surface of the CAM and did not invade the tissue where the secretion of the enzyme was not detected. The mortality rate of the chick embryo was not correlated with the degree of proteinase production of these strains. Two type Ib strains invaded the CAM tissue and elicited some tissue reactions by the host, yielding a low mortality rate of the chick embryos. These results suggested that the secretion of proteinase was an important factor for the invasion of CAM but other factors were also involved for the pathogenicity of C. albicans. PMID- 3328042 TI - Proteinase production and pathogenicity of Candida albicans. II. Virulence for mice of C. albicans strains of different proteinase activity. AB - We have studied the virulence for mice of Candida albicans strains with different proteinase activity in the culture. The mortality rates for mice infected with the type Ia strains, which secrete proteinase whose activity porsisted for a week in vitro, were higher than those infected with the type Ib strains, which secrete proteinase whose activity declined at 2 or 3 days in vitro and the type II proteinase-deficient strains. This was substantiated by the number of colony forming units (CFU) recovered from kidneys of mice infected with C. albicans. In the kidney tissues of mice infected with the type Ia strains, extensive invasion by fungal cells and the secretion of proteinase were histologically demonstrated, while in those infected with the type Ib and II strains fungal cells were rarely found. However, the mice infected with the type Ib strain NUM 978 were an exception; the recovery of CFU from the kidney was high, but the animals survived longer. Histologically, Candida cells were not colonized but interspersed in the tissue. Type II strain NUM 584 was found to be moderately virulent when infected at a high dose. These observations indicate that the proteinase plays a role in type Ia strains but that other factors are involved in the type Ib or II strains for the establishment of pathogenicity of C. albicans. PMID- 3328043 TI - Nucleotide sequence of the pnd gene in plasmid R483 and role of the pnd gene product in plasmolysis. AB - The pnd gene of R plasmid R483, like the srnB gene of the F plasmid, increases the degradation of stable RNA in Escherichia coli. The nucleotide sequence of the pnd locus was determined and compared with that of the srnB locus. The genes have open reading frames that are 54% homologous, and both have an upstream inverted repeat sequence. The pnd gene expression seems to decrease the osmotic barrier of the cytoplasmic membrane, since no plasmolytic vacuoles were formed in the cells carrying the gene when the cells were exposed to hypertonic sucrose solution. This result suggests that RNase I in the periplasm passes through the altered membrane to degrade stable RNA in the cytoplasm. PMID- 3328044 TI - [Molecular basis for constructing artificial immunogens]. AB - The molecular and cellular mechanisms of the effect of synthetic polyions on immunogenesis are discussed in the paper. The data on the basic properties of polyion immune stimulants and on the mechanisms of cellular reactions to these stimulants were used for constructing artificial antigen-polyion complexes having enhanced immunogenic properties. The vaccinating properties of a number of macromolecular complexes conjugated to bacterial and viral antigens are analyzed. PMID- 3328045 TI - [The correlation between biotype and antifungal sensitivity of Candida albicans]. PMID- 3328046 TI - Electronmicroscopic observation on protoplastization of Saccharomyces cerevisiae (uvarum) and Candida albicans under calcium deficiency. PMID- 3328047 TI - The effect of the morpholine derivate amorolfin (Roche 14-4767/002) on the ultrastructure of Candida albicans. PMID- 3328049 TI - Putting patients in the picture. PMID- 3328048 TI - Birth in the Bible. PMID- 3328050 TI - A child at risk. PMID- 3328051 TI - How to lift. PMID- 3328053 TI - Stroke. Interview by Laura Swaffield. PMID- 3328052 TI - Child centred nursing. PMID- 3328054 TI - Nursing under fire. PMID- 3328055 TI - Our shiftwork family. PMID- 3328056 TI - An ordinary life. PMID- 3328058 TI - Hepatitis B--at a glance. PMID- 3328059 TI - Coping with the death of a child. PMID- 3328057 TI - ABT: autologous blood transfusion. PMID- 3328062 TI - Nursing on the rocks. PMID- 3328061 TI - AIDS testing. PMID- 3328060 TI - A welcome reform: tailoring education to a nurse's need. PMID- 3328063 TI - Sickle cell disease. PMID- 3328064 TI - Standards in care. PMID- 3328065 TI - The need for sleep. PMID- 3328066 TI - Policing TB in the community. PMID- 3328067 TI - Measuring pain. PMID- 3328068 TI - Symptom relief: how you can help. PMID- 3328069 TI - AIDS and the nurse. PMID- 3328070 TI - Children in their proper place. PMID- 3328072 TI - Injection protection. PMID- 3328073 TI - Incontinence: what every nurse needs to know. PMID- 3328071 TI - Nursing Standard-Harris Poll survey: what's wrong with nursing? PMID- 3328074 TI - Dealing with normality. PMID- 3328077 TI - Professionally speaking. PMID- 3328075 TI - Student starter pack. PMID- 3328076 TI - Bringing up baby and keeping your career. PMID- 3328078 TI - Visual AIDS. Interview by Pauline Chudley. PMID- 3328079 TI - Rayner scrutiny. PMID- 3328081 TI - Urodynamic discoveries. PMID- 3328080 TI - Teach yourself nursing: how student nurses are often left alone in the ward to learn. PMID- 3328082 TI - Normal ageing. PMID- 3328083 TI - The human M.O.T.: how Oxfordshire is fighting heart disease. PMID- 3328084 TI - Have hospital, will travel. PMID- 3328085 TI - Little hole--big problem. PMID- 3328087 TI - Flexible friends. PMID- 3328086 TI - State of the union. PMID- 3328088 TI - Bad practice (to keep the blues away). Interview by Pauline Chudley. PMID- 3328089 TI - Taking control. PMID- 3328090 TI - Open learning. PMID- 3328092 TI - No place like home. PMID- 3328091 TI - What is deafness? PMID- 3328093 TI - Shift yourself. PMID- 3328094 TI - Raising a glass to retirement. Interview by Pauline Chudley. PMID- 3328095 TI - Stress. Interview by Pauline Chudley. PMID- 3328096 TI - Human frailties. Interview by Pauline Chudley. PMID- 3328097 TI - Rea of the Bailey. Interview by Pauline Chudley. PMID- 3328098 TI - [Selective posterior rhizotomy at the posterior radiculomedullary junction in the treatment of hyperspasticity and pain in the lower limbs]. AB - The authors report a series of 53 bedridden patients having harmful spasticity in one (6) or both (47) lower limb(s) and treated with selective posterior rhizotomy (SPR) in the dorsal root entry zone (DREZ). This severe spasticity was associated with irreducible flexion contracture in 49 cases and hyperextension in 3 others. 37 of these patients also had painful manifestations. The method was introduced in 1972 on the basis of anatomical studies of the DREZ in humans which showed a topographical segregation of the afferent roots according to their anatomico functional destinations. The technique consists of a 2 mm deep DREZ microsurgical cut directed at a 45 degree angle into the posterior lateral sulcus just ventral to DREZ and Lissauer's tract of the spinal cord. The procedure was carried out at each sensory rootlet considered to be responsible for the harmful spasticity and pain. SPR interrupts selectively the lateral nociceptive and central myotactic afferent fibers curving toward Lissauer's tract and the anterior spinal cord, while sparing most of the medial lemniscal fibers curving toward the dorsal columns, as well as the fibers of the inhibitory circuitry of Lissauer's tract and dorsal horn. The results were evaluated after a 1 to 14 year follow-up. Mild to severe complications occurred in 25 patients (47.1%) and were responsible for death in 5 (9.4%). Both spasticity and spasm were significantly decreased or completely eliminated in 75% and 88.2% respectively; when present, pain was relieved without a total suppression of sensation in 91.6%. These benefits combined with complementary orthopedic surgery in 23 patients--resulted in either a complete resolution or marked reduction of the abnormal postures and articular limitations (85.2% complete and 96.75 marked reduction). Because of the extreme severity of the pre-operative neurological deficits in almost all the patients in this series, surgery improved voluntary movements with a significant functional benefit in only 5 cases and vesico-sphincter function in none. Thanks to its valuable effects on hyperspasticity and pain, SPR in the DREZ made it possible for these very disable patients to be more comfortable in bed and wheel-chair and it allowed effective nursing and kinesitherapy to be resumed. PMID- 3328099 TI - [Value of bifocal stereotaxic destruction in case of dyskinesia in patients with a motor deficit of cerebral origin]. AB - Authors report a study concerning 12 dyskinetic patients with cerebral palsy. The clinical pre-operative examination shows that many signs and symptoms are associated: volitional and postural dyskinesia, athetosis and dystonia, pyramidal deficit and spasticity. Talairach's stereotactic methodology has been used for bifocal (VPL thalamic nucleus and internal pallidum) Yttrium 90 implantation. After stereotactic bifocal lesions, involuntary movements have been reduced in 45.5% of cases and have disappeared in 27% of cases. Impairment of previous motor deficit has been observed in 3% of cases; volitional and postural dyskinesia seems to be the most curable symptomatology. Clinical results in athetoid involuntary movements and dystonia are less rewarding. Because of important anatomical modifications often observed cerebral palsy patients, the authors stress the interest of individual acute neurophysiological study and discuss about the stereotactic targets and the modalities of destruction. They insist upon the necessity of rigorous selection of indications based on acute clinical examination in the perspective of improvement of global functional capacities. PMID- 3328100 TI - [Isolated dissection of the renal artery treated by conservative surgery in 3 patients]. AB - We reported 3 cases of male patients with isolated dissecting aneurysm of the renal artery. The clinical presentation included lumbar pain followed by hypertension (malignant in 2 cases) in the next 3 months. These three patients have underwent surgical renal artery repair. At maximal follow-up (4, 5, 11 years after surgery), the blood pressure was normalized in these 3 patients (with one antihypertensive drug in 2) and the renal function remained stable. PMID- 3328101 TI - [Cardiovascular risk of diuretics in the treatment of arterial hypertension]. AB - During the last 25 years, diuretics have been widely used with safety and efficacy in the treatment of arterial hypertension and edematous states. Nevertheless, recent intervention trials failed to show a significant decrease in mortality of ischemic heart disease in hypertensive patients given pharmacological treatment. These results led to reassessment of cardiovascular risks of antihypertensive drugs per se and particularly diuretics. Diuretics have a kaliuretic effect and long-term administration decreases serum potassium levels by 0.3 to 0.6 mmol/l. The long-term consequences of hypokaliemia are not well defined. The incidence of hypokaliema-induced ventricular arrhythmias has been studied with exercise or continuous ambulatory electrocardiograms but results are still conflicting. Patients with digitalis treatment, or with preexisting ischemic heart disease or left ventricular hypertrophy may be at high risk for developing ventricular arrhythmias. Glucose intolerance is related in part to the degree of hypokalemia and its incidence decreases with lower dosage of diuretics. Lipid disturbances including hypertriglyceridemia and increase in LDL-cholesterol have not been found to be persistent in long-term administration (1 yr or more) of diuretics. PMID- 3328102 TI - [Intravenous digital angiography in the kidney transplant patient: results of a systematic prospective study in 164 patients]. AB - A prospective study on digital intravenous angiography (DIVA) in 164 renal transplant recipients performed from 1 to 2 months post-transplant was conducted to assess its usefulness in the screening of post-transplant renal artery stenosis (RAS). DIVA was uninterpretable in 32 patients (19%) on technical grounds (blood vessel or metallic clip superimposed). The global prevalence of RAS was 10.7% in 132 patients whose DIVA was informative. No correlation was found between the prevalence of RAS and renal function. The prevalence of RAS was significantly higher (p less than 0.01) in the hypertensive (26%) than in the normotensive group (6.6%), but RAS may occur in normotensive or even asymptomatic patients. Our data confirm the usefulness of routine post-transplant renal artery screening but arterial way will be preferred. PMID- 3328103 TI - [Comparison of 3 high-permeability dialysers]. AB - Three capillary dialyzers, with highly permeable membranes, have been compared for their capacity of epuration of blood urea nitrogen, creatinine, phosphorus, uric acid and beta 2 microglobulin, and for their respective protein losses. There were very little differences between the dialyzers for epuration of small uremic molecules, with no benefit due to high permeability membranes in comparison with conventional dialyzers. Protein losses may be important and have to be known. About beta 2 microglobulin, filtered quantities are not correlated to changes in serum levels, suggesting the presence of other mechanisms (adsorption on the membrane and generation during hemodialysis) which influence, together with epuration, perdialytic changes of serum beta 2 microglobulin concentrations. PMID- 3328106 TI - [Intrauterine neurosurgical intervention in a case of congenital hydrocephalus]. AB - The authors point to new perspectives of fetosurgery development in Poland describing a case of hydrocephalus with intracranial haematoma treated by an intrauterine procedure under USG control. After birth the newborn was subjected to an operation for coexistent myelomeningocele and ventriculo-atrial shunt was implanted for prevention of secondary hydrocephalus development. Attention is called to the necessity of observation of indications to these operations, and precise ultrasonographic teratological diagnosis. Legal and deontological problems created by fetosurgery are discussed. PMID- 3328105 TI - [Late results of the treatment of multiple sclerosis with large doses of Enkorton]. AB - A group of MS patients treated with large doses of Prednisone (3960 mg over a period of 54 days with initial dose 200 mg per day) was observed during 4 years after the therapy and the results were compared with the control group treated with medium doses of Prednisone (initial dose 60 mg). The difference between two therapeutic groups estimated according to Kurtzke disability scale is statistically not significant. We cannot also conclude, that the large doses of Prednisone decrease the relapse rate. However it should be stressed that in patients treated with megadoses of Prednisone the secondary chronic progressive course of MS, more rarely developed than in cases treated with medium doses. PMID- 3328107 TI - [Sleep apnea syndromes]. PMID- 3328108 TI - Oncocytic transformation in papilloma of the choroid plexus. Light-microscopic study of 2 cases. PMID- 3328104 TI - [Diagnostic value of ultrasonography and ophthalmodynamometry in the diagnosis of stenosis and occlusion of the internal carotid artery]. AB - The results of ultrasonographic and ophthalmodynamometric investigations were evaluated in 40 patients with stenosis or occlusion of the internal carotid artery. An agreement was demonstrated between the results of ultrasonographic and angiographic investigations in 85% of cases, and between ophthalmodynamometric and angiographic findings in 65% of cases. In 20% of cases ophthalmodynamometrically silent occlusion of the internal carotid artery was demonstrated. These results show that supplementation of ophthalmodynamometric investigations with ultrasonography increases the proportion of correct diagnoses. PMID- 3328109 TI - [Consumption of coffee and ischemic cardiopathy. Review of the literature]. PMID- 3328111 TI - [Squamous papilloma of the esophagus]. PMID- 3328110 TI - [Study of the efficacy of l-sulpiride on dyspepsia and on the motor dynamics of the gallbladder. Controlled test versus domperidone]. PMID- 3328112 TI - [Diagnosis of a pregnant non-communicating rudimentary uterine horn in a woman requesting an abortion]. PMID- 3328113 TI - [Current aspects of hormone therapy in carcinoma of the breast]. PMID- 3328114 TI - [Post-micturition bladder residue after vaginal hysterectomy assessed by ultrasonographic method]. PMID- 3328115 TI - Food intolerance: our practice. AB - This paper describes the clinical presentation of food allergy and/or intolerance (F.A.I.). The role of a diagnostic dietary trial is reviewed. Finally dietary management is discussed. PMID- 3328116 TI - Are the changes of mood in children with coeliac disease due to abnormal serotonin metabolism? AB - Children with untreated coeliac disease are characteristically unhappy and after a few days of treatment with a gluten-free diet their mood improves. This improvement in mood can be rapidly reversed by introducing gluten into their diet again which suggests that a humoral agent could be involved in this process. As serotonin is a neurotransmitter in the brain and abnormalities of serotonin metabolism have been reported in coeliac disease, this biogenic amine could be the humoral agent that mediates the changes of mood in coeliac disease. In this review the relationship between the mood changes in coeliac disease and serotonin metabolism will be further examined. PMID- 3328117 TI - Food, growth and congenital heart disease. AB - The effect of congenital heart disease on growth is reviewed. Whether being small matters is questioned, and reasons why infants with congenital heart disease are small are discussed. Methods of improving growth, and catch-up growth are described. Finally management of the child with CHD and failure to thrive is considered. PMID- 3328118 TI - Nutritional management of infants and toddlers with chronic renal failure. AB - Normal renal function is an essential prerequisite for normal nutrition. Renal failure results in malnutrition and growth retardation, which are particularly marked when renal failure has its onset early in life. Conversely, the careful application of nutritional therapy can ameliorate the effects of renal failure and allow improved well being and growth and possibly retard the rate of progression of renal failure. Nutritional therapy includes the provision of an adequate energy intake, appropriate intakes of water, electrolytes, vitamins and minerals and regulation of protein and phosphorus intakes. In this paper the theoretical considerations underlying these objectives are reviewed and practical ways of achieving them with least disruption to the child and his family suggested. PMID- 3328119 TI - Galactosaemia. AB - This paper reviews galactosaemia and describes the experience of the Willink Biochemical Genetics Unit in the management of classical galactosaemia. Galactokinase and UDPgalactose-4-epimerase deficiency are dealt with briefly. The former disorder is readily treated with a galactose free diet and if this is started early in life, the only complication, cataracts, is avoided. Epimerase deficiency is a relatively 'new' disorder and little is known about the eventual outcome of affected patients. Early observations suggest that the prognosis is likely to be poor even in those patients diagnosed and treated soon after birth. Classical galactosaemia leads to a number of long term complications. The prognosis for normal mental development in affected patients is poor. Unfortunately this does not appear to be reversible by early diagnosis and treatment and whilst every effort should be made to establish an early diagnosis our experience suggests that there is no difference in the ultimate mental development between those who are detected within the first two weeks of life and those before the age of six weeks. In addition female homozygotes are at a very high risk of developing ovarian failure at an early age. PMID- 3328120 TI - Does it matter how we feed premature babies? AB - The multiplicity of dietary regimes available for low birthweight infants is a measure of clinical uncertainty in this field. The reasons for this persisting uncertainty are analysed: few studies have examined whether early diet matters in terms of clinical outcome; instead, management decisions have been based on short term 'physiological' studies on nutrient accretion, growth and metabolism. Data from this Unit's multicentre outcome trials on nearly 1000 preterm infants, randomly assigned to early diet, are used to demonstrate that whilst diet influences many aspects of the infants 'physiology' in the short term, such physiological responses have limited value in predicting clinical outcome. Preliminary data from the early follow-up of this cohort to 18 months post-term suggest that the diet used in the neonatal period may have persisting consequences in terms of motor and mental development and growth. The longer-term significance of these findings is being investigated. PMID- 3328121 TI - Foods, fads, and fats in under fives. AB - Does manipulation of a child's diet in the first five years of life result in a reduced prevalence of coronary artery disease in later life? The findings of a recently published study (Bogalusa) are compared with British recommendations. Suitable modifications of the under fives' diet are suggested. PMID- 3328122 TI - Surgical procedures for inflammatory tubal disease. AB - Microsurgical techniques using optical magnification and fine instruments in association with delicate tissue-handling yield improved success rates for tubal disease. This observation seems to be true despite the effects of tubal disease factors involving ovum pickup and transport. All data that seem to be comparable show nearly a twofold improvement in the success rate for distal and proximal disease and for salpingostomy, anastomosis, fimbriolysis, and salpingolysis. Of utmost importance are appropriate diagnosis and adequate evaluation of all fertility factors before recommendations are made for operation. Both the patient and her partner must be aware of the risks and the chances of success. Attempts should be made to determine all prognostic factors so that thorough discussion can be carried out and an informed patient is allowed to make the decision. Prospective studies should try to evaluate the specific factors that may be of importance in an attempt to improve the fertility of patients with diseased tubes. PMID- 3328123 TI - Reproductive uterine surgery. AB - Uterine reconstructive surgery may be accomplished through both the abdomen and the hysteroscope. It is important to obtain a complete evaluation of infertility or repeated pregnancy wastage prior to surgery. Newer approaches include the hysteroscopic resection of the uterine septum and medical therapy with GnRH analogues for reduction of fibroid size, volume, and symptoms. In some instances, larger fibroids may be approached through the hysteroscope or resectoscope after medical therapy. PMID- 3328124 TI - Immunologic infertility. AB - In general, the management of antibody-mediated infertility has been plagued by misdiagnosis due to the choice of assay system, therapies that may be associated with major side effects, and a failure to learn from the models of other antibody mediated diseases. An important consideration in diagnosing antibody-mediated infertility is to use an immunoglobulin-specific technique that employs intact or living spermatozoa. Once this is done, a search should be made for what functional deficits in reproduction are associated with the presence of the antisperm antibodies. This would include postcoital testing, tests for ovum penetration (human sperm/hamster egg penetration assay), and tests for the ability of the sperm in the presence of antibody to undergo the acrosome reaction. Once the extent of the reproductive deficit is known, appropriate therapy can then be suggested. I believe that a "case" must be built to prove that antibody-mediated fertility actually exists in a particular couple, even in the presence of a positive test that is known to be highly specific. Sperm antibodies can attach to the sperm's surface without detrimentally affecting reproductive function. In a similar vein, low levels of sperm antibodies could give a positive test result, but the level may be insufficient to be a major detriment to fertility. It is hoped that in the near future isolation of specific sperm antigens will be used to identify antibodies against antigens critical to reproductive function. It may be possible to determine the minimal amount of antisperm antibody that is necessary to disturb each individual step in reproductive function. If a patient is found to have sperm antibodies whose quantity exceeds this amount, then the patient can be appropriately labeled as having antibody-mediated infertility. The array of therapies available for the couple's unique fertility problem(s) can then be described to the patient, and an appropriate therapeutic choice made. PMID- 3328125 TI - In-vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). AB - In the past decade, the use of in-vitro fertilization and embryo transfer (IVF ET) procedures as a means of treatment of infertility has become a clinical reality. More recently, similar yet differing techniques have been described that further expand options of treatment of infertile couples. This article summarizes recent advances in IVF and compares it with the most widely recognized of these alternatives, gamete intrafallopian transfer (GIFT). In addition to comparing and contrasting these new technologies, the authors attempt to highlight unresolved questions about their use. PMID- 3328126 TI - Recurrent aneuploidic and euploidic abortion. AB - The evaluation of recurrent embryopathy in man is one of the most difficult tasks. The physician must clearly recognize which couples are experiencing recurrent euploidic abortion and which couples are experiencing recurrent aneuploidic abortion. A firm knowledge of the cytogenetic character of the abortion material enables one to make the next step, namely to determine the source of error in gametogenesis. Techniques are gradually becoming available to identify the source of the parental gametogenic area. In addition, new methods to detect molecular mutation in euploidic abortion are gradually evolving. The establishment of normal protein profiles by two-dimensional gel electrophoresis in normal abortions should enable one to screen recurrent embryopathy in man for abnormal proteins. Abnormal proteins, once identified, can enable us to identify the specific DNA mutation that may be at the heart of the problem. PMID- 3328128 TI - Luteal phase deficiency. An underdiagnosed and overtreated reproductive endocrine disorder. AB - Although luteal phase deficiency is rather time consuming, expensive, and sometimes painful to diagnose and treat, this disease entity is associated with a high degree of treatment success. Physicians are encouraged to become more aware of luteal phase deficiency as a potential diagnosis in the infertile woman. If the recommendations are followed in the diagnosis and treatment of luteal phase deficiency, a high degree of success can be achieved in infertile couples who otherwise would be diagnosed as having idiopathic infertility (and be ineffectively treated). PMID- 3328127 TI - Evaluation of the infertile couple. AB - Evaluation of the infertile couple involves confirming the diagnosis of infertility based on history and a review of coital practices. A complete examination should include the following components: general evaluation, history, physical examination, assessment of ovulatory factor, tubal factor, peritoneal factors, uterine factors, and cervical factor, and assessment of male factor. PMID- 3328129 TI - Cervical and uterine factors in infertility. AB - The uterus plays a pivotal role in many aspects of human reproduction. The cervix and its secretion are actively involved in sperm transport. Postcoital tests and other in-vitro and in-vivo tests evaluate sperm-cervical mucus interaction and should be an integral part of infertility investigation. Various diagnostic tests should help clinicians evaluate developmental and organic disorders of the uterine body. Adequate management of cervical and uterine factors in infertility is commonly rewarded by restoration of fertility in a high proportion of cases, when impairment of fertility is due to these conditions. PMID- 3328130 TI - Therapeutic insemination. AB - Except in special circumstances, therapeutic insemination with a husband's sample has a low success rate. Couples in whom oligozoospermia has been identified as the principal cause of infertility do not benefit from therapeutic insemination by husband. Because of this low success rate, intrauterine insemination to provide sperm in closer proximity to the egg has become popular, but intrauterine insemination also has a low success rate. We suggest that intrauterine insemination should be approached aggressively in cases of male factor infertility. The recipient should be stimulated to enhance egg production and closely monitored for ovulation. A semen specimen of not less than 1 X 10(6) motile sperm with antibiotics added should be placed in the uterus the day after ovulation. If no pregnancies occur within four cycles, alternate approaches should be considered. Therapeutic insemination by donor involves careful donor selection to avoid inheritance of malformations and familial diseases. Because of the possibilities of sexually transmitted diseases, careful and repeated screening should be conducted. A complete sexual history should be obtained, and donors should be excluded if they have had any homosexual contact since 1978, if they have been an intravenous drug user, if they come from a geographic area where the sex ratio of AIDS is close to 1:1, or if they have recently had multiple sexual partners. A permanent record preserving the confidentiality but allowing the tracing of genetic anomalies, even if not present at birth, should be kept. PMID- 3328132 TI - Current concepts and treatment of hyperprolactinemia. AB - The present information relative to hyperprolactinemia is designed to give the reader insight into the possible central abnormalities occurring in women with elevated prolactin levels. It appears that in the presence of elevated prolactin levels appropriate testing should evaluate the pituitary gland, and that this should be performed in association with thyroid function studies. The treatment of high prolactin levels is mainly based on the clinical findings, but in most of the instances, a medical approach utilizing bromocriptine appears to be advantageous. Long-term results appear to indicate that bromocriptine is effective with a wide margin of safety. PMID- 3328133 TI - Pelvic endometriosis. AB - The recent heightened interest in endometriosis has led to remarkable progress in the elucidation of the pathophysiology of this enigmatic disease. Presently, it is not clear why some individuals with endometriosis develop infertility and pelvic pain, whereas others with a similar degree of disease do not. Several tantalizing clues have been extracted from studies of the molecular pathogenesis, immunology, and biochemistry of endometriosis. Investigations are now under way to determine the specific relevance to infertility of macrophage aggregation; prostaglandin and related metabolite production by endometriotic lesions and macrophages; specific factors released by endometriosis that might directly impair ovum pick-up, fertilization, embryo transfer, or implantation; and ovulatory dysfunction including luteal phase deficiency and LUFS. There are probably a host of potential mechanisms of infertility in endometriosis; additional research should enable us to determine their regulatory features and to formulate effective clinical intervention. We now have a broader array of options for the treatment of endometriosis than ever before. However, most of the extant reported clinical experience consists of case reports and limited series of patients without the use of controls, follow-up intervals, and appropriate statistical analysis. The diverse course and presentation of the disease have limited our ability to develop a staging system that provides consistent scoring among different clinicians and appropriate relative emphasis on the various manifestations of the disease. Some additional resolution will be necessary to assess the relative contribution to infertility by fresh and recurrent lesions, endometriomas, and adhesions. These problems are now in sharp focus, and data should be available in the future giving us an accurate appraisal of the clinical effectiveness of danazol, gestrinone, GnRH analogues, conservative surgery, laparoscopic surgery including use of the laser, IVF-ET, and GIFT. Also, it is anticipated that potentially fertile patients with endometriosis might be identified so that they could avoid therapy altogether. PMID- 3328131 TI - Polycystic ovarian disease. AB - Polycystic ovarian disease has a variety of biochemical and clinical features with great individual variation. In our clinical experience, oligo-ovulation, manifested as oligomenorrhea or frank amenorrhea, associated with an acyclic estrogen milieu, is a consistent finding. This may be associated with hyperandrogenemia, hirsutism, inappropriate gonadotropin levels, hyperprolactinemia, obesity, insulin resistance, and ultrasound evidence of multicystic enlarged ovaries. A common presentation is infertility or irregular menstruation secondary to oligo-ovulation and hirsutism secondary to altered androgen metabolism. A challenge in diagnosis is to differentiate polycystic ovarian disease from latent cases of congenital adrenal hyperplasia. Although the precise mechanism in the pathogenesis of polycystic ovarian disease remains undefined, altered function of the hypothalamic-pituitary-ovarian and adrenal axes is both involved and integrated. Results from clinical trials of ovulation induction using different agents have implicated one site or another as the major progenitor of the "vicious cycle" but with no definitive pathway established. Restoring fertility to these patients can be challenging in that not all patients with polycystic ovarian disease respond to clomiphene or do so satisfactorily. The use of glucocorticoid suppression, pituitary suppression with GnRH analogues, or the use of FSH alone may be of benefit in clomiphene treatment failures. PMID- 3328134 TI - [Refractive changes and correction of ametropia after penetrating keratoplasty]. PMID- 3328135 TI - A new donor cornea marker and punch for penetrating keratoplasty. AB - We describe a new device to mark and punch donor corneas for penetrating keratoplasty. The device contains eight marking-suction holes that make circular marks in the periphery of the donor cornea and fix the tissue in position during trephination. The eight peripheral marks correspond in location to meridians of an eight-blade radial keratotomy marker. When used in conjunction with this marker for the host bed, the donor cornea marker facilitates alignment of meridians on donor and host tissues, radial placement of sutures, and quantitative placement of sutures equi-distant from the wound margin. PMID- 3328136 TI - A comparative study of the growth of Campylobacter fetus strains in liquid media. AB - The growth of C. fetus fetus, C. fetus venerealis and C. fetus venerealis biotype intermedius was examined in 10 liquid media. From the data obtained, a 10% inoculum size and an oxygen level of 6% seemed imperative for consistent growth, especially for the C. fetus venerealis strain. A lowered redox potential obtained by the addition of 0, 1% cysteine-HC1 to the media was stimulatory. The medium which yielded the best growth was the one described by Dennis & Jones (1959). The fastidious C. fetus venerealis strain yielded maximum values of 0,5% packed cell volumes after 48 h cultivation in a microaerophilic atmosphere on this medium. The other strains yielded higher values. PMID- 3328137 TI - [Epineural and perineural nerve suture in children]. PMID- 3328138 TI - Human leukocyte antigens: an update on structure, function and nomenclature. AB - The study of human leukocyte antigens, predominantly by monoclonal antibody techniques, is a rapidly changing area of basic research and clinical investigation. This review outlines some of the results and trends of research in this field. Of particular importance is the updating of the current nomenclature. The CD classification of these antigens has become the standard form in published literature and provides a basis for standardization of clinical reporting. The current CD classification is presented in the form of a list, with a brief summary of each antigen beside each entry. The results reviewed range from the section on CD1 antigen in which the data presented are primarily concerned with the underlying biology of the antigens to the section on clinical application which has little biological content. PMID- 3328139 TI - Immunohistological evaluation of MHC class I and II antigen expression on nevi and melanoma: relation to biology of melanoma. AB - MHC antigen expression on 20 nevi, and 35 primary and 95 metastatic melanomas was studied by immunoperoxidase techniques using monoclonal antibodies to identify the antigens on frozen tissue sections. DR antigens were not detected on nevi but were detected on 71% of primary melanomas and 56% of metastases, suggesting that this antigen may be a useful marker of malignant transformation of nevi. Expression of class II antigen could not be related to other prognostic histological features of primary melanoma such as tumour thickness, but comparison of the common phenotypes of primary and metastatic melanoma suggested that expression of DR antigens alone in the absence of DP, DQ and ABC antigens may be an indicator of metastatic potential. Class I (HLA-A,B,C) antigens were also expressed infrequently on nevi but were detected on 43% of primary melanomas and 34% of metastases. HLA-A,B,C expression was inversely related to thickness of the primary melanoma. This as well as the lower expression of class I antigens on metastases, may indicate that growth and spread of melanoma may be inhibited by MHC (class I) dependent cytotoxic T cell responses. Expression of class I MHC antigens was unrelated to class II antigens. Expression of DR was more common than DP or DQ, but the latter with one exception, were not expressed in the absence of DR antigens. Significant differences were not found in MHC antigen expression on metastases in lymph nodes compared to those in subcutaneous sites, but further studies are needed to determine whether such differences may exist between metastases in other visceral sites. PMID- 3328140 TI - Autoantibody to aldolase in acute and chronic hepatitis. AB - Sera from 82 patients with acute or chronic hepatitis and 40 chronic carriers of hepatitis B were examined by ELISA and immunoblotting for reactivity with the glycolytic enzyme aldolase. The results of the ELISA tests, expressed as a percentage of a positive control, were compared to those obtained with sera from 39 patients with rubella, 11 with cytomegalovirus infection and 74 healthy subjects. The ELISA reaction with sera, expressed as mean +/- standard deviation was, for 15 patients with hepatitis A, 58.3 +/- 20.5%; 15 with hepatitis B, 59.5 +/- 42.18; 23 with hepatitis non-A, non-B 51.1 +/- 34.4%; 11 with HBsAg positive chronic active hepatitis, 70.1 +/- 31.5%; and 17 with autoimmune chronic active hepatitis, 66.8 +/- 21.4%. All values were significantly (p less than 0.05-p - less than 0.001) higher than those obtained with sera from carriers of hepatitis B surface antigen, 25.6 +/- 27.2%; rubella, 21.1 +/- 20.0%; cytomegalovirus infection, 19.2 +/- 27.8%; or healthy subjects, 20.9 +/- 16.2%. In two randomly selected sera, reactivity with aldolase by ELISA was neutralized by absorption with the enzyme. Selected sera showing reactivity by ELISA reacted by immunoblotting with aldolase. The findings suggest that acute or chronic liver damage may provoke the production of autoantibodies to aldolase. PMID- 3328142 TI - Cysteine requirements of naturally occurring cysteine auxotrophs of Escherichia coli. AB - The requirements for cysteine of naturally occurring cysteine auxotrophs of Escherichia coli were determined in a defined liquid medium. Maximal growth was obtained in the presence of cysteine concentrations between 20 and 250 mg/l. At concentrations below 20 mg/l growth of the auxotrophs, but not the prototrophic control, was suboptimal in this system. In the presence of cysteine concentrations in excess of 250 mg/l, growth of both auxotrophic and prototrophic E. coli was inhibited with lower growth yields, a decreased specific growth rate and an extended lag phase being observed. These effects were minimised in the presence of 2 mM L-leucine, L-isoleucine and L-valine. PMID- 3328141 TI - Complete Freund's adjuvant has a differential amplification action on the induction of diabetes by streptozotocin in various murine strains: CFA amplifies STZ in murine diabetes. AB - The effect of complete Freunds Adjuvant (CFA) has been investigated on the multi low-dose streptozotocin (STZ) model of diabetes in mice of the H-2b (C57Bl/6) and of the H-2k (A/J, CBA) genotypes. Physiological (glycemia and body weight) and morphological (insulitis) parameters were monitored. STZ was used at standard and sub-diabetogenic dose levels (45 and 22.5 mg/kg STZ, for five consecutive days respectively) and CFA was given as a single dose (0.1 ml) on the first dosage day. In H-2k mice, CFA was synergistic with STZ at 45 mg/kg but did not cause the 22.5 mg/kg dose to raise glycemia to diabetic levels. By comparison, CFA was not synergistic with STZ at 45 mg/kg in H-2b mice, but did convert the subdiabetogenic dose to a diabetogenic action in these animals. Histologically, it was noted that insulitis was a more prominent and persistent feature of the H 2k mice. It occurred at the subdiabetogenic dose level of STZ in H-2k mice, in the absence of increased glycemia, suggesting that these two phenomena are not related. CFA, either alone, or with STZ, caused severe persistent perilobular inflammation of the exocrine pancreas. It did not increase the incidence or severity of insulitis. A possible mechanism whereby CFA is synergistic with STZ at different doses in H-2b and H-2k mice is suggested. PMID- 3328144 TI - Detection of alpha-1-antitrypsin in hepatocytes in acute and chronic hepatitis. AB - Twelve of sixteen consecutive needle biopsies of liver with either acute or chronic hepatitis showed positive immunohistochemical staining for alpha-1 antitrypsin (AAT). Only two of the positive biopsies contained numerous, large periodic acid-Schiff positive, diastase resistant (PAS-D) globules in periportal hepatocytes; both patients were Pi MZ but only one had a low serum AAT concentration. The other 15 patients had normal or elevated serum AAT. The accumulation of AAT in hepatocytes, demonstrated by sensitive immunohistochemical staining, may indicate increased synthesis and/or impaired secretion of AAT occurring in association with various types of hepatitis. PMID- 3328143 TI - Observer variability in microcomputer-assisted morphometric study of nuclear parameters. AB - To evaluate observer variability during microcomputer-assisted planimetry, nuclear features (area, perimeter, and form factor) were studied in a case of malignant lymphoma. Tissue fixed in glutaraldehyde, embedded in plastic and sectioned at 1 micron was studied using a Zeiss Kontron IBAS 2000 image analysis system. Manual tracing of nuclear outline was performed to obtain the parameters. Both interindividual and intraindividual reproducibilities were evaluated, the former among 8 observers and the latter by the observers repeating the measurements. With the present technique, intraindividual reproducibility was high and correlation was excellent for area, perimeter and form factor measurements. A high degree of interindividual inconsistency was demonstrated for all parameters. Interindividual correlation was poor for form factor. It is concluded that poor interindividual reproducibility even when the objective method of morphometry is used may be a significant problem in tissue investigations, especially when results from different laboratories are being compared. PMID- 3328145 TI - [Prostaglandins and the heart]. PMID- 3328146 TI - [Effect of subdiaphragmatic vagotomy on the enteroinsular axis]. PMID- 3328147 TI - [A method of preparing routine histologic specimens for examination using a scanning electron microscope and roentgenologic microanalyser]. PMID- 3328148 TI - [Current theories on various disorders of uric acid metabolism in the body]. PMID- 3328149 TI - [Hyperammonemias of childhood. I. Enzymopathies of the urea cycle]. PMID- 3328150 TI - [A simple method of controlling the psychomotor development of children up to 5 years of age using the Lingam method]. PMID- 3328151 TI - [The history of one of Warsaw's hospitals during the 1944 Uprising and its later fate. II]. PMID- 3328153 TI - [Current theories on the pathogenesis of celiac disease]. PMID- 3328152 TI - [Achievements of the science of pediatrics in the Ukraine]. PMID- 3328155 TI - [Neo-natal chylothorax: antenatal echographic diagnosis and favourable outcome]. AB - A case of right chylothorax in a male neonate is reported. A sonographic diagnosis was made during the 35th week of pregnancy. A complete recovery was obtained with appropriate dietetic therapy. PMID- 3328154 TI - [The role of immunosuppressive agents in the treatment of nephrosis in children]. AB - Good clinical results are well known with the use of immunosuppressive therapy in children with idiopathic nephrotic syndrome; more recently, biological data have enhanced immunological anomalies, concerning mainly T helper lymphocytes. The need for steroids may decrease when relapsing nephrotic syndrome is associated with steroid intoxication and is absent when corticoresistance occurs. In these cases, the use of immunosuppressive agents is justified, but limited by side effects and toxicity. In patients treated with alkylating agents and now cyclosporine, good responses are often seen in frequently relapsing children whereas the course of steroid-resistant nephrotic syndrome is not significantly modified. However, the definite appreciation of such therapeutic results has to be further precised by both histological data and multicentric studies concerning new protocols. PMID- 3328157 TI - [Interstitial pulmonary fibrosis of unknown etiology]. PMID- 3328156 TI - [Ovarian cyst in newborn infants: what attitude should we adopt? (apropos of 8 cases)]. AB - With the advent of routine fetal ultrasonography, the frequency of prenatal diagnosis of ovarian cysts has considerably increased. Based upon a personal experience of 8 cases and a review of published series, the authors discuss the management of perinatal ovarian cysts. Before birth punction of the cyst under sonographic guidance or cesarean delivery may be considered in order to avoid the rupture during normal delivery. After birth, surgery should be performed in case or voluminous or complicated cyst or uncertain diagnosis. Homogenuos medium sized cysts or cysts with functional cytology should be followed by echography, before surgery being considered. PMID- 3328158 TI - [Food allergy and psychosomatic medicine. New frontiers]. AB - Within the area of psychosomatic and behaviour disorders in childhood, a few problems worthy of clinical investigation in order to investigate the hypothetical role of trophoallergy: colics, hyporexia, and sleep disorders within the first year of life; toddler diarrhoea and irritable bowel syndrome; hyperactivity, learning disabilities, migraine and tension fatigue syndrome in later years. Personal data and literature strongly supporting a causative role of food allergy in a significant percentage of such a kind of cases are presented. The possible pathways, and the guide-lines for a clinical approach are presented. PMID- 3328159 TI - [Clinical features of food allergy in children]. AB - Food allergy (FA) (especially cow's milk allergy) is a frequent complaint in children. The clinical features of FA are protean and depend not only on the organ predisposition, but also on the immunological mechanism involved in the reaction. In this paper, the Authors review current knowledge regarding the clinical spectrum of FA in children, focusing the attention not only on classic clinical syndromes like anaphylaxis, atopic dermatitis and enteropathies, but also discussing less known problems like FA in breast feed infants, respiratory complaints, unusual gastrointestinal manifestations, cortical hyperostosis and also behavioural disturbances. PMID- 3328160 TI - [Headache in childhood with special reference to migraine. Discussion of a personal case material of 94 subjects]. AB - After having characterized epidemiologically, etiopathogenetically diagnostically, prognostically and psychologically the childhood headache, the A.A. refer data relative to 94 children of age in between 6 and 16 years, of which 51 females and 43 males, suffering for migraine (diagnosed by Bille's criteria). The ratio between migraine and sex, age, relationships, clinical symptomatology, onset time, crisis appearance frequency and causing factors have been studied. The relations between migraine and spasmophilia have been treated with particular remark in our casuistry, since similar studies don't appear in the literature. The work ends with some informations about migraine's common therapy, our particular one and the results that we obtained. PMID- 3328161 TI - [Transient alkaline hyperphosphatemia of childhood. Description of a clinical case]. AB - Transient idiopathic alkaline hyperphosphatasemia is a syndrome of unknown etiology unrelated to any specific disease, characterized by a marked transient increase of the serum level of alkaline phosphatase. About fifty-two cases of them included from thirty-seven to two months have been reported in Literature till now. A new case of a little girl four years and three months old is reported here. PMID- 3328163 TI - [Retroperitoneal teratoma. Description of a case]. AB - The Authors describe a case of asymptomatic retroperitoneal teratoma discovered on a routine examination in a six year-old male. Diagnosis was made pre operatively on the base of CT scan imaging. Surgery allowed radical excision of the teratoma, which turned to be a totally benign entity. PMID- 3328164 TI - Topical minoxidil in the treatment of male pattern alopecia. AB - Male pattern hair loss (androgenetic alopecia) is a common problem. In fact, it affects nearly all males to some degree. Expression of the disorder is variable, and while it is never life-threatening, it often becomes a major source of consternation. The biology of the process is poorly understood, and no current therapy can halt or reverse the process. Only cosmetic surgery, which is painful, time consuming, and expensive, has been effective. In the past 7 years, since it was noted that a patient taking minoxidil for hypertension had reversal of male pattern hair loss, awareness of a possible therapeutic role for topical minoxidil in the management of this disorder has grown among physicians, scientists, and the general public. It can be concluded from available data that topical application of minoxidil is effective in providing cosmetically satisfying thickening of hair in a select group of individuals with male pattern hair loss. The drug's mechanism of action remains obscure. No serious side effects have been demonstrated with its use, however, and it is therefore advised in selected patients. PMID- 3328162 TI - [Osteomyelitis and arthritis caused by Streptococcus group B in a 40-day-old boy]. AB - Group B streptococci (GBS) have gained much attention in recent years as a cause of serious infection in the newborn. Traditionally two clinical syndromes have been defined as "early onset", with fulminant septicemia, pneumonia and meningitis, and "late onset", with a mild meningitis. More recently some previously unrecognized clinical presentations of GBS disease have been documented. These include asymptomatic bacteremia, septic arthritis, osteomyelitis, ethmoiditis with orbital cellulitis, pneumoniae with empyema, conjunctivitis. The literature to date reports 30 instances of osteomyelitis due to GBS. This report describes a forty days infant with a group B streptococcal osteomyelitis of the proximal humerus. Has been also emphasized the increased frequency and the benign clinical course of streptococcal osteomyelitis in the neonate. PMID- 3328165 TI - Lovastatin: a new cholesterol-lowering agent. AB - Lovastatin is a potent new drug for lowering serum cholesterol through inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme for cholesterol biosynthesis. Metabolic studies with lovastatin in healthy volunteers and patients with hypercholesterolemia suggest reduced synthesis of low-density lipoprotein cholesterol (LDL-C) as well as enhanced catabolism LDL-C mediated through LDL receptors as the principal mechanisms for lipid-lowering effects. Total cholesterol and LDL-C are reduced by 30% or more on average when added to baseline therapy, with the effects being more pronounced in nonfamilial than in familial hypercholesterolemia. Optimal dosing appears to be 20 mg given twice a day. The most common adverse effects are gastrointestinal, while the most serious are elevated transaminase levels and the potential for lens opacities. Lovastatin is the first of a new class of lipid-lowering agents, and is effective when added to diet therapy or in combination with other drugs. PMID- 3328167 TI - Immunologic effects of cimetidine: potential uses. AB - Suppressor T lymphocytes play a major regulatory role in the function of the immune system. Since the discovery of histamine (H2) receptors on the surface of these immune cells, studies have demonstrated that cimetidine diminishes the effect of suppressor T cells in both cellular- and humoral-mediated (antibody) immune reactions. Preliminary clinical results demonstrate that cimetidine has a beneficial effect on a variety of immune functions. An antineoplastic effect among tumor-bearing animals has also been found, suggesting the drug may be effective against certain human cancers, probably as an immune potentiator. Cimetidine has been used in the treatment of human cancer in combination with interferon or coumarin and as a single agent. Modest tumor response rates have been observed. The finding that cimetidine accelerates healing of herpesvirus infections is intriguing. These encouraging, albeit preliminary, results emphasize the need for additional studies on the drug's antiviral properties. PMID- 3328166 TI - Stress-related mucosal damage: critical evaluation of potential new therapeutic agents. AB - Cell injury produced by hydrochloric acid is the final common denominator for stress-related mucosal damage. Actions of therapeutic agents designed to prevent such damage are directed toward either inhibiting acid secretion or stimulating protective mechanisms. Newer agents that fall into the former category include omeprazole, an inhibitor of the H+-K+-ATPase pump, prostaglandins, and somatostatin. In addition to inhibiting acid, prostaglandins stimulate mucus and bicarbonate secretion and therefore provide a two-pronged protective action. Tranexamic acid is an antifibrinolytic agent that is postulated to promote clotting at bleeding sites in upper gastrointestinal lesions. Analyses of composite data suggest that (1) prostaglandin E preparations appear to be as effective as currently recognized forms of therapy, such as antacid and H2 receptor antagonist administration; (2) little enthusiasm can currently be generated for use of somatostatin or tranexamic acid; and (3) omeprazole is a theoretically attractive agent that remains to be tested in the prophylactic treatment of gastrointestinal ulceration due to severe stress. PMID- 3328170 TI - Recognizing, setting therapeutic goals, and selecting therapy for the prevention and treatment of stress-related mucosal damage. AB - Advances in the care of critically ill patients and in diagnostic techniques, such as fiberoptic endoscopy, have enabled greater recognition of stress-related mucosal damage (SRMD). This condition is distinguished from chronic peptic ulcer disease by its greater number of lesions, proximal location in the acid-producing portion of the stomach, and superficial bleeding. Endoscopy is considered the best method for detecting and monitoring mucosal damage. The onset of SRMD occurs early, within hours of the traumatic insult. Pharmacologic treatment has been oriented toward suppressing intraluminal acid and enhancing mucosal defense mechanisms. Antacid therapy is considered the best method for treatment of SRMD, although extensive experience has been gained with the H2-receptor antagonists. The vast majority of experience with the H2-receptor antagonists has been with cimetidine, which is as effective as antacids, as shown by endoscopy. Investigations of alternative forms of therapy (e.g., prostaglandins) are in progress. PMID- 3328169 TI - Pathophysiology and mechanisms of stress ulcer injury. AB - Stress ulceration, a disease associated with the stress of severe injury, sepsis, and organ failure, has declined in frequency during the last decade. Factors contributing to this decrease include more rapid transport of trauma patients, early resuscitation, avoidance and treatment of complications, and prophylactic maintenance of increased gastric mucosal pH. The pathophysiology of these lesions remains to be elucidated completely; however, both aggressive factors (acid, duodenal reflux, etc.) and a deficiency in defensive mechanisms (gastric mucosal blood flow, gastric mucosal barrier, mucus, bicarbonate, etc.) play a role in their inception. The hemorrhagic complication of stress ulcer, which is usually seen between the fifth and tenth days after admission, remains a sequela associated with a significant rate of mortality. PMID- 3328168 TI - Potential use of cimetidine for treatment of acetaminophen overdose. AB - Acetaminophen, a drug frequently taken in intentional and accidental overdose, causes liver toxicity when concentration of the cytochrome P-450-derived metabolite exceeds the metabolic capacity of available glutathione. Present treatment of acetaminophen overdose involves oral N-acetylcysteine (NAC), which enhances liver glutathione synthesis. An alternative or additive approach to therapy would be to inhibit the formation of the toxic metabolite by inhibiting the cytochrome P-450 system. The H2-receptor antagonist cimetidine inhibits the cytochrome P-450 system, does not interfere with the administration or function of NAC, and therefore affords additive protection. Also, it has little effect on the nontoxic routes of elimination of acetaminophen and is itself quite nontoxic. That cimetidine protects against acetaminophen toxicity in animal models has been demonstrated on the basis of improved survival, as well as decreases in several critical elements used to monitor acetaminophen toxicity: classic histologic changes, aminotransferase activity, metabolite covalent binding, and liver glutathione depletion. Administration of cimetidine well after the overdose is also protective. In contrast, animal models of acetaminophen toxicity demonstrate that ranitidine does not afford protection from acetaminophen hepatotoxicity. Clinical data in well-done trials in humans will be needed to support the experimental animal data. PMID- 3328171 TI - Cosmetic solaria and malignancies of the skin. PMID- 3328173 TI - Dark effect of 8-methoxypsoralen on lymphocyte surface markers. PMID- 3328172 TI - Passive transfer of photosensitivity by intradermal injection of vesiculobullous lupus erythematosus serum and ultraviolet light irradiation in the guinea pig. AB - To study the effect of ultraviolet light (UVL) exposure on the pathogenesis of vesiculobullous lupus erythematosus (VBLE), the back of depilated Strain 2 female guinea pigs was injected with sera from 2 patients with VBLE, 3 patients with non bullous systemic lupus erythematosus (SLE) (disease control) and 4 normal human adults (normal control). Normal saline was also used as an additional control. Of the 20 injected areas, only half (10) were then irradiated with one minimal erythema dose of UVB (310 nm). The clinical and histologic features of the areas injected with VBLE sera and then irradiated showed significant differences from the areas only injected, as well as from the areas receiving injection and irradiation of the control sera (both disease and normal). Immunofluorescence studies, on the other hand, showed similar results in the areas injected with either VBLE or SLE sera. These results suggest that the most likely mechanism for induction of VBLE blisters is photoactivation of circulating factor(s) that damage the dermoepidermal junction of both sun-exposed and non-sun-exposed skin. PMID- 3328175 TI - [Pathogenesis of acute ischemic kidney failure]. PMID- 3328174 TI - An adaptation of the Candida albicans phototoxicity test to demonstrate photosensitizer action spectra. AB - The Candida albicans assay is widely used for the testing of potential photosensitizers, especially furocoumarins. A novel adaptation of this assay is described which provides a rapid, inexpensive and easy-to-perform method of producing action spectra. The use of filter paper rectangles with central apertures instead of the usual discs, and monochromatic irradiation with a liquid light guide reduces some of the problems associated with the standard assay. Action spectra for 8-methoxypsoralen and a new pyrrolocoumarin derivative are presented as illustrative examples. PMID- 3328176 TI - [Pathogenesis of chronic kidney failure]. PMID- 3328177 TI - [Problems of anesthesia in patients with chronic kidney failure]. PMID- 3328178 TI - [Treatment of patients with disorders of the biotransformation function of the liver with (+)-cyanidanol-3]. PMID- 3328179 TI - [Hepatological update (7). 2 different phases of chronic hepatitis B--2 different methods of treatment?]. PMID- 3328181 TI - [Myocardial ischemia without anginal pains]. PMID- 3328182 TI - [Dietary proteins and kidney function. Pathophysiological and therapeutic aspects]. PMID- 3328180 TI - [Value of fendiline in the treatment of patients with stable angina pectoris]. PMID- 3328183 TI - [Hereditary orotic aciduria]. PMID- 3328184 TI - Diseases of the nails in children. PMID- 3328186 TI - The Sturge-Weber syndrome. AB - The Sturge-Weber syndrome is characterized by angiomas of the leptomeninges overlying the cerebral cortex in association with a facial nevus flammeus. Although frequently included with other neurocutaneous genodermatoses, the syndrome is almost always sporadic in occurrence. The most common associated neurologic abnormality is seizures, which are controlled in more than 50% of patients by the administration of anticonvulsants. Laser therapy is the most promising therapeutic option for cosmetic management of the facial nevus flammeus. PMID- 3328185 TI - Sarcoidosis in children. AB - Sarcoidosis is a multisystem disease of unknown etiology that is rarely diagnosed in children. When mass screening is performed, the incidence of the disease in children approaches that of adults with similar demographics. Most childhood cases occur around ages 9 to 15 years, with small clusters of cases occurring in children under age 4 years. The disease in these two age groups has very different clinical features. Children under age 4 have a clinical triad of rash, arthritis, and uveitis. The classic syndrome in older children involves primarily lungs, lymph nodes, and eyes. In older children, constitutional symptoms (fatigue, lethargy, malaise) and pulmonary symptoms (cough, dyspnea) predominate. Mortality in childhood sarcoidosis is about 5%, with long-term sequelae in 10% to 20%. Early recognition may prevent complications such as blindness, pulmonary insufficiency, and renal impairment. PMID- 3328187 TI - Childhood bullous lichen planus. AB - A child with previous lichenoid lesions had bullae refractory to antistaphylococcal antibiotics. Biopsy of a bulla showed histologic changes of bullous lichen planus. Indirect immunofluorescence using the patient's serum on a perilesional bulla biopsy showed positive staining for IgA and IgG in the stratum granulosum and stratum corneum, confirming the diagnosis. The lesions resolved with dapsone treatment. PMID- 3328188 TI - Diagnosis and decisions--can we do better? PMID- 3328189 TI - The clinical use of cerebrospinal fluid studies in demyelinating neurological diseases. AB - The clinical diagnosis of definite multiple sclerosis is supported by abnormalities in the cerebrospinal fluid: variable mild pleocytosis and elevation of total protein, moderately elevated total IgG in most patients, and the almost invariable presence of discrete immunoglobulins after electrophoresis, the oligoclonal bands. The oligoclonal bands are non-specific, and are seen in most diseases of the nervous system, but their temporal uniformity in each patient with multiple sclerosis is characteristic. Prognostically, patients with a single episode of optic neuritis or paraesthesia who have oligoclonal bands are more likely to develop multiple sclerosis than if the spinal fluid were normal. In the Guillain-Barre syndrome, the spinal fluid total protein is transiently elevated, with no pleocytosis. Oligoclonal bands are usually found in the acute phase and only persist in those patients with chronic or relapsing polyneuropathy. PMID- 3328191 TI - Pulmonary berylliosis on corticosteroid therapy, with cavitating lung lesions and aspergillomata--report on a fatal case. AB - A fatal case of pulmonary berylliosis in a 42 year old male is described. The patient was exposed to beryllium while working in a chemical plant over a 9 year period, and presented two years after ceasing such employment. The berylliosis was diagnosed on open lung biopsy in 1971. The patient was commenced on steriod therapy at that time. He suffered progressive dyspnoea from severe restrictive lung disease over the next 14 years. A chest X-ray of June 1985 revealed a lesion in the left upper lobe suggestive of a mycetoma. Before any therapy could be instituted he suffered a massive haemoptysis and died. Post-mortem examination revealed two large mycetomata in the right and left upper lobes. Parenchymal histology showed evidence of chronic inflammation with non-caseating granulomata and the cavity wall showed localized invasion by Aspergillus fumigatus. It is possible that the long term steroid therapy with multiple boosters of treatment may have contributed to the development of the mycetoma. This is the first case report known to the authors of a fatal aspergilloma in association with chronic berylliosis treated with steroids. PMID- 3328190 TI - Investigation of cereal toxicity in coeliac disease. AB - Coeliac disease is exacerbated by wheat gluten. A review of methods for the purification, identification and quantitation of wheat proteins to investigate coeliac disease is presented. Recent developments including amino acid sequencing and expression of wheat protein peptides in E. coli should permit characterization of the cereal peptide that exacerbates coeliac disease. PMID- 3328192 TI - Acute renal failure following Yersinia pseudotuberculosis septicaemia. AB - Although Yersinia pseudotuberculosis has not been previously reported to cause acute renal failure, it accounted for two cases reported here out of eighty referrals with acute renal failure to our renal unit over the last year. This may suggest that the incidence of Yersinia pseudotuberculosis may be greater than that previously reported, and it should be suspected in patients presenting with bloody diarrhoea in association with renal failure. The septicaemic form of the disease is life threatening and requires intensive supportive therapy. PMID- 3328193 TI - [The course of compulsive disease in childhood and adolescence]. PMID- 3328194 TI - [Contested childhood--on the discussion of the long-term effects of early experiences]. PMID- 3328195 TI - [Peter Villaume (1746-1825): a pedagogue of enlightenment as forerunner of behavior therapy in children]. PMID- 3328196 TI - [Improvement of bacteriological diagnosis of tuberculosis using new nutrient media]. PMID- 3328197 TI - [On the 100th anniversary of the birth of V. S. Khol'tsman]. PMID- 3328199 TI - Major depression associated with endocrine disease. AB - The discovery of specific behavioral effects of several neuropeptides and the expanded appreciation of a wide range of endocrine disturbances in depressive illness have recently renewed interest in the nature of the relationship between mood and endocrine changes. Major depressive disorders are a major and life threatening complication of Cushing's syndrome, Addison's disease, hyperthyroidism, hypothyroidism and hyperprolactinemic amenorrhea. A treatment primarily directed to the physical condition may be more effective than antidepressant drugs in such organic affective syndromes. The influence of hormonal disturbances in the development of depression in Conn's disease, pheochromocytoma, parathyroid disturbances, SIADH, acromegaly, hirsutism and other endocrine diseases should be individually evaluated. Antidepressant drugs remain the most specific and readily available treatment of major depressive disorders in the setting of endocrine illness. PMID- 3328198 TI - Psychiatric aspects of epilepsy. AB - The relationship between epilepsy and psychiatry is reviewed. It is concluded that patients with epilepsy display more psychopathology than control populations and that patients with temporal lobe epilepsy are especially susceptible to more severe psychiatric illness. Psychosis, particularly with a schizophrenia-like presentation seems associated with dominant hemisphere pathology especially with altered function. The relationship between personality disorder and epilepsy is less clear. Affective disorder is a common clinical problem, although earlier reports of a link with the non-dominant hemisphere have not been replicated in some recent studies. The problem of cognitive decline is examined and it is concluded that many patients with epilepsy show either selective or more generalized impairments of abilities. This may be related to the effects of anticonvulsant drugs, and the possibility that carbamazepine may possess psychotropic properties is noted. PMID- 3328200 TI - The structure of psychopharmacological revolutions. AB - Thomas Kuhn's model of the structure of scientific procedure is outlined and applied to salient aspects of recent psychopharmacological research into the bioneural substrates of the affective disorders. It is argued that the amine hypotheses of these disorders are irrefutable in practice although not in principle and that their survival despite a lack of convincing supporting evidence and dis-proof of their initial premises suggests that they serve a paradigmatic function and that the core of this paradigm is psychological in nature rather than neurobiological. An attempt is made to show how an awareness of such functions may help explain otherwise puzzling features of the literature on the psychopharmacology of the affective disorders. Such an awareness may also help to indicate the steps necessary to replace the amine hypotheses or the likely future prospects for these hypotheses. PMID- 3328202 TI - PGI2-receptors and molecular mechanisms in platelets and vasculature: state of the art. PMID- 3328201 TI - Some aspects of respiratory allergy in certain areas of China. PMID- 3328203 TI - [Elemental-organic combinations in medicine]. PMID- 3328204 TI - [Drugs and the body (VI)--Transdermal therapeutic systems]. PMID- 3328205 TI - Recent developments in iodophor disinfectants. PMID- 3328206 TI - [Determination of insulin release from triglyceride suppositories by radiochemical means]. PMID- 3328207 TI - [The etio-epigenetic nosographic system as an illustration of multiaxial diagnosis in psychiatry]. AB - Basing on earlier work done by Essen-Moller in Sweden, Leme Lopez in Brazil, and Tadeusz Bilikiewicz in Poland, a survey is presented of the development of the concepts known an etioepigenetic psychiatric nosography. The significance of these systems in the classification of mental disorders is illustrated by examples. The etioepigenetic system involves three axes of development methods of the complex structure of the psyche. The first axis embraoes the genotypic period, the second the effects of etioepigenetic factors, and the third the formation of psychopathologic (neurotic or psychiatric) syndromes. PMID- 3328208 TI - [Computerized tomography and infusion test as a simultaneous study method in post traumatic hydrocephalus]. AB - The cerebral compression of a patient with posttraumatic hydrocephalus was measured intraventricularly, and an intrathecas infusion test was made simultaneously with computed tomography. Substractive computed tomography pictures show that continuously increasing volume does not imply uniform enlargement of the ventricular system, the cornua of the lateral ventricles in particular exhibiting a frontal increase in size. PMID- 3328209 TI - [Adolf Strumpell and the issue of "traumatic neurosis"]. AB - By his introduction of the term "psychisches Trauma", Strumpell exerted an influence on Oppenheims concept of traumatic neurosis. What he termed "Begehrensvorstellungen", too, had an important part to play in the ensuing discussion on the origin of traumatic neuroses. That the two sides in dispute nonetheless appealed to the authority of the internist and neurologist Strumpell in matters of expert opinion, is an indication of his discernment in these problematic open questions. PMID- 3328210 TI - Strongyloides stercoralis hyperinfection syndrome: how often is it missed? PMID- 3328211 TI - Recent advances in the management of fungal infections. PMID- 3328212 TI - Cardiac failure in the elderly. PMID- 3328213 TI - Reversal of severe neurological manifestations of Wilson's disease following orthotopic liver transplantation. AB - Experience with liver transplantation for patients with Wilson's disease who have major neurological impairment is limited, and this report describes the results obtained in two such patients. The first was a 30-year-old man with a 14-month history of hepatic and neurological impairment. In spite of treatment with d penicillamine, he developed increasing dysarthria, dysphagia, akinesia and rigidity of all four limbs, and required continuous nursing care. Following transplantation, liver function was almost normal from four weeks onwards, but recovery of neurological function was much slower and was not seen until two to three months after surgery. By four months he was sufficiently mobile to be discharged, and when he returned for assessment at eight months, no abnormal neurological signs were detectable. The second patient was a 27-year-old woman with worsening liver dysfunction for eight years; one year previously she had developed dysarthria, akinesia, a fine tremor and moderate rigidity of all limbs as well as marked psychological impairment. There was no improvement on treatment with d-penicillamine or trientine, but as liver function returned to normal two months after liver grafting, her neurological and psychological function began to improve so that by three months she could be discharged. PMID- 3328215 TI - Hypothesis testing in ecology: psychological aspects and the importance of theory maturation. AB - Proper hypothesis testing is the subject of much debate in ecology. According to studies in cognitive psychology, confirmation bias (a tendency to seek confirming evidence) and theory tenacity (persistent belief in a theory in spite of contrary evidence) pervasively influence actual problem solving and hypothesis testing, often interfering with effective testing of alternative hypotheses. On the other hand, these psychological factors play a positive role in the process of theory maturation by helping to protect and nurture a new idea until it is suitable for critical evaluation. As a theory matures it increases in empirical content and its predictions become more distinct. Efficient hypothesis testing is often not possible when theories are in an immature state, as is the case in much of ecology. Problem areas in ecology are examined in light of these considerations, including failure to publish negative results, misuses of mathematical models, confusion resulting from ambiguous terms (such as "diversity" and "niche"), and biases against new ideas. PMID- 3328214 TI - Treatment of myasthenia gravis: an audit. AB - Although treatment of myasthenia gravis with anticholinesterase drugs and thymectomy was based on wrong models of pathogenesis the resulting saving of life has not been improved by immunosuppressive treatment based on a current autoimmune model. Immunosuppression with steroids or azathioprine may reduce morbidity but as these drugs can rarely be withdrawn without causing relapse, the long-term hazards are serious, including increased mortality. PMID- 3328216 TI - [Use of the effective equivalent dose for assessing the risk to patients of radiodiagnosis]. PMID- 3328217 TI - [The chronology of scientific life. 50 years of biophysics]. PMID- 3328218 TI - Current and potential indications for Ca2+ antagonists. PMID- 3328219 TI - Threads of cultural nutrition: arts and humanities. AB - Cultural nutrition encompasses a wide sweep of food-related themes within three major categories: arts and humanities, social sciences, and biological-natural sciences. The paper, first of three, considers the arts and humanities. Topics include food and diet expressed through art, film, music, and dance. The essay then examines food and diet in representative works of literature, both ancient and modern. The place of food and diet within folklore, mythology, and religion is treated, with consideration of symbolic roles played by food throughout the human life cycle, especially with birth and infancy, coming-of-age, marriage, and death. Religion, a major theme in cultural nutrition, is explored and the food dietary patterns of Jews, Christians, Moslems, Hindus, and Shintos are treated. Ethics and philosophy are examined as both relate to programs of international food relief and vegetarianism. The essay concludes with a review of work by historians, especially themes of famine and approaches taken to refeed populations during combat and hostilities. PMID- 3328220 TI - Women, nutrition and exercise: a review of athletes' intakes and a discussion of energy balance in active women. AB - Given the heightened interest in nutritional aspects of exercise, and an increase in athletic participation by women, it appeared timely to review the nutritional implications of exercise in women. The initial part of this paper contains a compilation of published studies on the nutrient intakes of female athletes. These reveal that most groups of athletes have adequate nutrient intakes, and that their vitamin and mineral intakes appear to be superior to those of nonathletic women. The average energy intake of athletes in studies summarized in this paper was 2069 kcal, and for certain groups of athletes, energy intakes were even lower. How these women manage to train intensely while consuming energy intakes similar to those of sedentary women is not readily apparent, and for this reason, the remainder of the paper discusses energy balance as affected by activity. Methodological considerations related to assessment of the components of the energy balance equation (food intake, energy expenditure, and body energy stores) are presented, with a focus on considerations in women. The effects of activity on each of these components are then discussed in an attempt to determine whether some form of energy conservation may occur. Finally, effects of activity on the menstrual cycle are reviewed. The observed changes are discussed in relation to nutrition 1) in terms of how nutrition may play a role in their causation; and 2) in terms of their nutritional implications for the amenorrheic athlete, specifically as regards energy balance and bone density. PMID- 3328222 TI - [The history of the development of electrophoresis in Uppsala]. PMID- 3328221 TI - Metal protein interactions. AB - Proteins associated with metals serve many important biological functions. The amino acid residues provide the functional groups in a protein which are the potential ligands for a metallic cation. Metals impart various effects on protein structure and bring about overall structural stability. These effects are seen in quarternary, secondary and tertiary structures of the protein. There are varieties of approaches to study metal protein interactions. The earliest technique being the equilibrium dialysis which is still used extensibly to determine the binding strength and the number of metals bound per protein molecule. There are a number of other techniques available which provide precise information about the nature of metal binding sites. They include electron spin resonance, UV and visible spectoscopy, nuclear magnetic resonance, resonance Raman, X-ray crystallography, X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (XAFS), etc. Selected metal protein interactions are discussed in this review. Albumin is the major plasma protein in blood which transports a number of metals. Detailed studies of Cu(II) and Ni(II) binding to albumin suggests that both metals have the same specific binding site at the NH2-terminal tripeptide sequence (Asp1-Ala2-His3...) involving the Asp alpha-NH2, His3 N (1) imidazole, two deprotonated peptide nitrogens (Ala2NH and His3NH), and Asp1 COO- group. Transferrin transports Fe(III) in blood. The protein possesses two metal-binding sites, each within a domain of bilobal proteins. Presence of carbonate is an important feature of Fe(III)-binding to transferrin. The binding site has been postulated as one involving Tyr 185 and Tyr 188 and suggests that two of the three histidines His 119, His 207 and His 249 also serve as ligands. Arginine 145 is a likely anchor for the carbonate anion. Superoxide dismutase is an enzyme found in erythrocytes which catalyzes the dismutation of superoxide radical. The protein is a dimer made up of two equivalent subunits. The subunits are held together by noncovalent interactions. For optimal enzymatic activity, at least two of the protein's four metal ions must be cupric. The results of the X-ray crystal structural analysis for Cu(II) and Zn(II) containing protein have been reported. In the metal-binding region of one subunit, Cu(II) and Zn(II) are separated by approximately 6A. The Cu(II) is bound to imidazole side chains of histidines 44, 46, 61 and 118 in a distorted square planar arrangement. The imidazole ring of histidine 61 is believed to be deprotonated and to serve as a bridge between Cu(II) and Zn(II).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3328223 TI - Primary cerebral histiocytosis X: case report. PMID- 3328224 TI - Prevalence of cholelithiasis in diabetes mellitus: a cholecystosonographic study. PMID- 3328225 TI - Complete duplication of the male urethra: report of a case and review of the literature. PMID- 3328227 TI - Radiobiological considerations of total body irradiation in bone marrow transplant conditioning: hyperfractionation of dose and early results. PMID- 3328226 TI - Radiation therapy of cancer of paranasal sinuses: a report on 86 patients. PMID- 3328228 TI - A trial of automatic kidney detection in a dynamic renal study. AB - We developed an automatic kidney detection procedure designed to do away with extraneous margins such as the liver or spleen while leaving the kidney margins intact using Laplacian operations and concurrence calculations. We evaluated the detectability of kidneys using our procedures and found that the renal margins were successfully detected in 84 cases of 100 subjects (84%) including 176 kidneys out of a total of 198 kidneys (89%). It was shown that as the renal function decreased the detectability of the renal margin decreased. In eight cases (16 kidneys) out of 9 patients who later resultantly received hemodialysis even manual settings of the renal ROI were very difficult. After excluding these 8 cases the detectability was 92% for all the cases and 95% for the kidneys. It was our conclusion that this method is sufficient for clinical application. PMID- 3328229 TI - [Use of the natural abundance of stable isotopes in animal physiology]. PMID- 3328230 TI - [Introduction to experiments on genetic engineering. II. Preparation of competence cells for DNA-transformation]. PMID- 3328232 TI - [Osteoclasia and resorptions. Review of the literature]. PMID- 3328233 TI - [Comparative evaluation of apical seal obtained in vitro using the Canal Finder System]. PMID- 3328231 TI - [Calcium hydroxide in endodontics]. PMID- 3328234 TI - [Clodomiro Picado and the evolution of the concept of autoantibodies]. PMID- 3328235 TI - [Growth hormone. Human or biosynthetic?]. PMID- 3328236 TI - [Platelet antibodies in idiopathic thrombocytopenic purpura in children]. PMID- 3328237 TI - [Evaluation of the routine administration of antibiotics in infants with acute lower respiratory infections]. PMID- 3328238 TI - [Prevalence of bacteriuria in preschool children]. PMID- 3328239 TI - [Usefulness of C-reactive protein in the early diagnosis and follow-up of severe neonatal infections]. PMID- 3328241 TI - [Current aspects of blast injuries to the ear]. PMID- 3328240 TI - Proteinuria in the dog: a pathomorphological study of 51 proteinuric dogs. AB - Renal cortical biopsies of 51 dogs with spontaneous proteinuria were examined by histology, electron microscopy and immunofluorescence. Glomerular lesions were classified in four groups: mesangioproliferative, membranoproliferative and membranous glomerulonephritis and amyloidosis. The glomerular and the tubulointerstitial lesions were graded, using a semiquantitative system. The results were used for the calculation of correlation coefficients between several parameters. A positive correlation was found between the severity of glomerular and tubulointerstitial lesions. Fibrin detection by immunofluorescence and histochemical methods appeared not to be correlated. The presence of electron dense deposits correlated only with the fluorescence for IgG and C3. Fluorescence for IgA and IgM was frequently observed in cases with or without dense deposits. PMID- 3328242 TI - [Double-blind clinical valuation of Actisoufre by endonasal route with nasosinusal ultrasonography]. PMID- 3328243 TI - The testicular biopsy in the evaluation of male infertility. AB - A testicular biopsy is often useful in male infertility to evaluate the degree of damage and the patient's prognosis. The major issues in the interpretation of the histologic specimens are the adoption of a simple reproducible classification of testicular abnormalities, and the recognition of specific causes of damage. This review is concerned with the clinical scope of testicular biopsy for infertility, the technical handling of the specimen, and a practical stepwise approach to the histologic diagnosis. PMID- 3328244 TI - Intratubular germ cell neoplasia. AB - Intratubular germ cell neoplasia is now well established as a precursor to invasive germ cell tumors of the testis. The lesion is usually associated with subsequent development of typical invasive tumors if orchiectomy is not performed. Pathologic findings in intratubular neoplasia consist of germ cell abnormalities within the seminiferous tubules. The atypical cells have large round nuclei, prominent nucleoli, and abundant clear cytoplasm. They have ultrastructural and immunohistochemical characteristics of spermatogenic precursor cells present in the fetal and postnatal testis. Intratubular collections of abnormal germ cells have been found adjacent to invasive germ cell tumors in a high proportion of cases. Intratubular neoplasia occurring in the absence of testicular enlargement has been found in the following situations: cryptorchidism, in testes of some infertile men, dysgenetic testes, and in the contralateral testis following orchiectomy for germ cell cancer. Recognition of intratubular germ cell neoplasia is of special importance because detection of the most common forms of testicular cancer can be accomplished at a preinvasive stage and, therefore, prior to the opportunity for metastasis. PMID- 3328245 TI - The role of IgG, IgM, and C3 in experimental murine IgA nephropathy. PMID- 3328247 TI - Do local hemodynamic alterations mediate injury in IgA nephropathy? PMID- 3328246 TI - IgA-associated renal diseases: immunochemical studies of IgA1 proteins, circulating immune complexes, and cellular interactions. PMID- 3328248 TI - Evolution of IgA glomerulonephritis: relation to morphology, immunogenetics, and BP. PMID- 3328249 TI - [Retroperitoneal tumors]. PMID- 3328250 TI - [Cutaneous complications in a diabetic patient treated by the insulin pump. Value of an 100 U/ml insulin preparation]. PMID- 3328251 TI - [Macrolides and immunity]. AB - In order to counteract an ever increasing bacterial resistance, a new trend in antibiotic therapy is to try and obtain compounds with "immunostimulating" properties. Although the macrolides have been known for more than 30 years, their interaction with the host defence system has been poorly investigated. These drugs display an outstanding ability to penetrate and concentrate in phagocytes. Few depressive effects on phagocyte functions have been reported, while some macrolides have been shown to exert an immunostimulating effect in vitro and ex vivo. The data published on this subject are summarized in this review paper. Further studies would be required for a better understanding of structure immunomodulating activity relationships. PMID- 3328253 TI - [Simultaneous myeloma in husband and wife. Description and review of the literature]. PMID- 3328252 TI - [New aspects of macrolides: contribution of roxithromycin]. AB - Roxithromycin (RU 28965) is a new semi-synthetic derivative of erythromycin. Its antibacterial activity is of the same order as that of other macrolides, although its MIC's against Legionella pneumophila are lower. In double-blind comparative studies there was no significant difference in therapeutic effectiveness between roxithromycin and the reference antibiotics tested. However, this new macrolide exhibits exceptional pharmacological properties (prolonged half-life, excellent tissue penetration and intracellular activity), and it is very well tolerated both clinically and biochemically. PMID- 3328254 TI - [Radionuclides and protective diets]. PMID- 3328255 TI - [Facts and hypotheses on the mechanism of synaptic release of the mediator]. PMID- 3328257 TI - [Experimental studies of clinical psychology in psychiatric evaluation]. PMID- 3328256 TI - [Epidemiologic research and diagnostic criteria in psychiatry]. PMID- 3328258 TI - [Progressive cranial fracture]. PMID- 3328259 TI - [Forms of health education during gnatho-prosthetic treatment]. PMID- 3328260 TI - [Influence of casting forces on the structure of implements used in dental practice]. PMID- 3328261 TI - [A manuscript of homemade drug recipes from the 18th century]. PMID- 3328263 TI - [Interview granted by Prof. Gheorghe Chipail from IMF Iasi to Prof. C. Gh. Marinescu, chairman of the methodologic office of the alumni of IMF Iasi]. PMID- 3328262 TI - [Treatment with digitalis in chronic atrial fibrillation]. PMID- 3328264 TI - [Prof. Gheorghe Nastase. Centenary of his birth (1887-1987)]. PMID- 3328265 TI - [Current status of surgery of portal hypertension]. PMID- 3328267 TI - [Chronic infection by hepatitis B virus and development of primary carcinoma of the liver]. PMID- 3328266 TI - [Orthotopic liver transplant in dogs. The importance of using a veno-venous portasystemic shunt]. PMID- 3328268 TI - [Physiology of intestinal transport: recent advances (I)]. PMID- 3328269 TI - [Retrospective remembrance and citations of gastroenterology. The future]. PMID- 3328270 TI - Physiopathogenesis of chronic subdural hematomas: a new look to an old problem. AB - The genesis and development of a CSDH are presently explained in terms of a) neoformation of a subdural membrane; b) abnormal vascular permeability; c) defective local hemostasis (hyperfibrinolysis) and chronic rebleeding. Many etiological factors are involved, mechanical, hematogenic and vasogenic in nature. Both clinical and experimental evidence supports the hypothesis that hormonal factors, in addition to the above mentioned ones, could play a role in the pathogenesis of CSDHs. PMID- 3328271 TI - [High signal intensity of flowing blood in MR tomograms as an indication of changed flow characteristics]. AB - A case report points to a venous obstruction expressed by high signal intensities in the MR tomogram that had not been noted so far when using this method. PMID- 3328272 TI - [Jan Evangelista Purkinje 1787-1869]. PMID- 3328274 TI - Therapeutic plasmapheresis (review of the literature and own clinical experience). PMID- 3328273 TI - [Observations on the medical collection in the library of J.E. Purkinje]. PMID- 3328275 TI - History of the Purkyne fibres in the heart. On the occasion of bicentenary of Jan Evangelista Purkyne's birth (December 17, 1787). PMID- 3328276 TI - Hormonal therapy in postmenopausal women. PMID- 3328277 TI - Dexamethasone suppression test in psychiatry. PMID- 3328278 TI - Our experience, technique and indication for meniscus suture. PMID- 3328279 TI - Gastroduodenal ulcer disease. Aetiology, symptomatology, complications and diagnostics. PMID- 3328280 TI - Quality assurance in clinical chemistry. PMID- 3328281 TI - Gastroprotection by sucralfate against acetylsalicylic acid in humans. Role of endogenous prostaglandins. AB - Sucralfate has been shown to prevent the formation of acute gastric lesions induced by nonsteroidal antiinflammatory drugs such as aspirin (ASA) in animals, but little is known about the prevention by this agent of ASA-induced gastric damage in humans. This report describes the effects of sucralfate on mucosal formation of prostaglandins (PG), gastric microbleeding and DNA loss in intact and ASA-challenged stomach. Two groups of 12 healthy volunteers were used in a double-blind, placebo controlled trial to assess the effects of sucralfate 1.0g qid on the stomach in subjects without (group A) and with administration of 2.5g ASA during 2 days (group B). Sucralfate treatment during 4 days significantly reduced spontaneous gastric bleeding and DNA loss in group A and prevented blood loss caused by ASA in group B. The protective effects of sucralfate on spontaneous gastric blood loss were accompanied by increased mucosal biosynthesis and luminal release of PGE2 and 6-keto-PGF1 alpha with decreased release of TXB2. In ASA-treated subjects mucosal generation and luminal release of PG and TXB2 were greatly suppressed and sucralfate treatment did not influence these PGs in spite of the decreased mucosal damage. It is concluded that sucralfate has a potent protective action on spontaneous and ASA-treated gastric bleeding in man and that this protection may be partly due to the increased mucosal biosynthesis of prostaglandins. PMID- 3328282 TI - Clinical efficacy of sucralfate in reflux oesophagitis. AB - Sucralfate has been evaluated in reflux esophagitis. The rationale for its effectiveness is based on its protective adherence to denuded mucosal surfaces and its bile salt binding properties. According to Weiss et al (5), healing occurred in 72% and improvement in 14% of sucralfate treated patients, compared respectively to 40% and 20% receiving placebo (p less than 0.05). According to Laitinen et al (6) esophagitis healed in 53% of patients receiving sucralfate, against 34% of an alginate/antacid-treated group. Symptoms disappeared, or improved in almost 70% of both groups. Hameeteman et al (7) found improvement of esophagitis in 53% and healing in 31% after sucralfate, compared with 67% and 14% respectively after cimetidine. Symptomatic improvement was good and comparable in both groups. Simon et al (8) found endoscopic healing in 64% and improvement in 27% of sucralfate-healed patients, compared with 68% and 21% respectively after ranitidine. Symptom relief and antacid consumption was comparable in both groups. Sucralfate appears to be a safe and efficacious locally active mucosal protecting agent for the treatment of reflux esophagitis. Its efficacy is comparable to that of H2-receptor blockers. PMID- 3328283 TI - The efficacy, safety and dosage of sucralfate in ulcer therapy. AB - This paper reviews the results of placebo and cimetidine/ranitidine controlled studies in the short-term healing and maintenance therapy of duodenal (DU) and gastric (GU) ulcer, the status of newer dosage regimens, and safety aspects of the drug. The efficacy of sucralfate 1g qid in DU and GU healing has been amply confirmed in placebo and cimetidine or ranitidine-controlled studies. Healing rates have been reported in 60 to 83% DU patients after 4 weeks treatment with sucralfate but as with other drugs the rates tend to be lower in GU patients. The DU relapse rate after sucralfate healing is perhaps lower than after cimetidine healing, and sucralfate healing rates in DU are not compromised by concomitant cimetidine therapy, or by smoking. The value of maintenance therapy with sucralfate 1 g bd in reducing the relapse rate in patients with recently healed DU is well documented. The relapse rate is reduced from the order of 60 to 20% after 6 months, and from 81% to about 30% after one year. Available data also suggests that sucralfate is at least as effective as cimetidine in maintenance therapy. Sucralfate is effective in the prevention of GU relapse in the dose of 1g in the morning and 2g nocte. Sucralfate is particularly well tolerated. Constipation occurs in 2% of patients and nausea is occasionally encountered. The more convenient dose of sucralfate 2g bd is as effective as the conventional one of 1g qid in DU healing and recent evidence suggests that a single nocturnal dose of 2g nocte offers effective maintenance therapy in DU and GU disease. PMID- 3328284 TI - Treatment of peptic ulcers--acid reduction or cytoprotection? AB - In a Swedish multicenter double blind trial cimetidine was compared to sucralfate in the treatment of peptic ulcer. Patients with endoscopically verified gastric, prepyloric and duodenal ulcers were treated with cimetidine 400 mg x 2 or sucralfate 1 g x 4 for four to eight weeks. Gastric ulcers were treated up to 12 weeks. Patients with healed ulcers were followed for up to 12 months. During follow-up without any anti ulcer treatment control endoscopy was performed 2-4 and 9-11 months after endoscopic healing and at symptomatic recurrence. 647 patients were studied (334 cimetidine and 313 sucralfate). 258 patients were included in the 12 months' follow up: of these 143 were previously treated with cimetidine and 115 with sucralfate. Healing rates were 92% in patients treated with cimetidine and 87% in those given sucralfate (ns). Symptomatic relief and ulcer recurrence did not differ between the treatments. Smoking significantly increased recurrence rate and shortened the time to recurrence in the cimetidine treated patients, but not in the sucralfate group. Cimetidine and sucralfate compared well in all aspects of acute peptic ulcer treatment and recurrence during one year of follow up. PMID- 3328285 TI - Efficacy of sucralfate in the prevention of recurrence of peptic ulcer--double blind multicenter study with cimetidine. AB - A double blind, multicenter, six-month maintenance study was performed to assess the efficacy and safety of sucralfate (S), cimetidine (C), and their combination (S + C) in the prevention of peptic ulcer recurrence in a six-month observation period. 127 patients with gastric ulcer (GU) (group S: 39, group S + C: 48, group C:40) and 103 patients with duodenal ulcer (DU) (group S: 35, group S + C: 36, group C:32) were available for statistical analysis. Six to 12 months after healing of GU, the cumulative recurrence prevention rates by Kaplan-Meier method were 89.7----80.3% in group S, 97.6----72.6% in group S + C, 84.5----44.6% in group C. In duodenal ulcer they were 75.9----41.9% in group S, 87.8----47.7% in group S + C, 80.8----40.5% in group C. These results indicate that maintenance therapies of S and S + C are effective and safe for the prevention of gastric ulcer recurrence. PMID- 3328286 TI - Sucralfate versus cimetidine in duodenal ulcer--factors affecting healing and relapse. AB - An understanding of the factors affecting duodenal ulcer healing by different pharmacological agents should give some insight into the underlying pathophysiology of healing. PMID- 3328287 TI - Urodynamic aspects of continent urinary diversion. Review. AB - Continence following urinary diversion depends on factors related to the reservoir and outlet. The reservoir should possess good compliance and no or atmost low pressured phasic contractions. The outlet should provide adequate outflow resistance to allow expulsion of urine under voluntary control and at convenient intervals. Overcoming high intra-reservoir pressures by producing high outlet resistance may endanger the upper urinary tracts. There is evidence that a low pressure reservoir may be constructed from any part of the bowel as long as detubularization of the segment is performed. All types of intussuscepted valves possess an inherent tendency to dessuscept despite various techniques which are employed to stabilize them. The causes are discussed and a recently described technique to overcome this problem is reviewed. PMID- 3328288 TI - Ceftazidime as prophylactic treatment in renal stone surgery. Clinical evaluation and pharmacokinetics in renal tissue. AB - The effect of ceftazidime in surgery of renal stones associated with urinary tract infection was investigated and its pharmacokinetics in serum and renal tissue was compared in 14 patients (15 kidneys) operated on for renal calculi associated with multiple urinary tract infection. Two to four days preoperatively ureteric catheterization was performed to localize the level of the infection and 2 g of ceftazidime was given intravenously twice daily for 10 days. Renal biopsy, serum samples and in one patient renal lymphatic fluid were taken simultaneously for antibiotic assay. Urine cultures were performed at regular intervals pre- and postoperatively. Ten patients had bacterial growth in the stone-carrying renal pelvis. The same strain was found in the bladder as in the pelvis. Nine patients had sterile urine after 3-5 days of treatment. One patient with bilateral stones did not get sterile urine until after seven days of treatment. Bacterial growth was found in two out of six cultured stones obtained from patients with bacterial growth in the pelvis. The decreases in concentration of ceftazidime in serum and renal tissue seemed to be parallel. Slight reversible elevation of liver transaminases was noted in 5/14 patients. It is concluded that the concentration of ceftazidime in serum parallels that in renal tissue. Ceftazidime seems to be an effective prophylactic in renal stone surgery and the preoperative dose should be given close to the operation. PMID- 3328290 TI - [Jan Evangelista Purkinje and forensic medicine]. PMID- 3328291 TI - [Maternal deprivation manifested through children's drawings]. PMID- 3328289 TI - Necrotizing fasciitis: a serious soft tissue infection. PMID- 3328292 TI - [Great October--the most important event in the 20th century]. PMID- 3328293 TI - [Great October and health services for the working people]. PMID- 3328294 TI - [Achievements of Soviet surgery]. PMID- 3328295 TI - [Achievements and prospects of the development of internal medicine]. PMID- 3328296 TI - [Anti-tuberculosis measures during the past 70 years]. PMID- 3328298 TI - [Advances in Soviet health resort medicine]. PMID- 3328297 TI - [70 years of Soviet endocrinology]. PMID- 3328299 TI - [Stages in the development of Soviet medicine during the past 70 years]. PMID- 3328300 TI - [Pathological anatomy: current status and the prospects of its development]. PMID- 3328301 TI - [Immunologic response to streptococcal cell wall proteins in rheumatoid arthritis]. PMID- 3328302 TI - [The functional state of the thyroid in autoimmune thyroiditis]. PMID- 3328304 TI - [The use of expectorant agents]. PMID- 3328303 TI - [Development of higher medical education during the 70-year Soviet rule]. PMID- 3328305 TI - [Method for determining the degree of suppurative wound contamination by direct phase contrast microscopy]. PMID- 3328307 TI - [Extraintestinal complications of nonspecific ulcerative colitis and Crohn's disease]. PMID- 3328306 TI - [Alcohol and progeny]. PMID- 3328308 TI - [Role of immune changes in thyroid diseases]. PMID- 3328309 TI - [Echocardiography for the prognosis of acute myocardial infarct (based on the results of using an algorithm for image recognition)]. PMID- 3328311 TI - [A direct, rapid method for the identification of Streptococcus pyogenes from throat smears]. PMID- 3328310 TI - [Taeniasis and cysticercosis in Mexico (a bibliographic review)]. PMID- 3328312 TI - [Streptococcal angina, rheumatic fever and rheumatic heart disease]. PMID- 3328313 TI - [Timothy grass in the respiratory tract in children]. PMID- 3328314 TI - [Importance of preparation for childbirth]. PMID- 3328316 TI - Neodymium:YAG laser iridotomy. AB - During the past several years the Neodymium:YAG laser has become increasingly popular for performing peripheral iridotomy. Using energy levels of 2-8 millijoules per shot and 1-3 shots per treatment, most irides can be penetrated in one sitting. Nd:YAG laser iridotomies show very little tendency to close, except in patients with active intraocular inflammation. A small amount of hemorrhage is common following YAG laser iridotomy, but clinically significant hyphema is rare. Significant lenticular or corneal damage is extremely rare. Although longterm follow-up of large numbers of patients is lacking, Nd:YAG laser iridotomy appears to be a safe and effective alternative to Argon laser iridotomy in selected patients. PMID- 3328315 TI - Wound healing in glaucoma filtering surgery. AB - Successful glaucoma filtering surgery is characterized by the passage of aqueous humor from the anterior chamber to the subconjunctival space, which results in the formation of a filtering bleb. Aqueous in the subconjunctival space may then exit by multiple pathways. Bleb failure most often results from fibroblast proliferation and subconjunctival fibrosis. Factors associated with an increased risk of bleb failure include youth, aphakia, active anterior segment neovascularization, inflammation, previously failed glaucoma filtering surgery, and, possibly, race. Several surgical and pharmacologic techniques have recently been introduced to enhance success in eyes with poor surgical prognoses. To elucidate the scientific rationale of these methods, we summarize the process of wound healing after glaucoma filtering surgery and describe postoperative clinical and histopathologic features, factors which may affect success, and specific methods to improve surgical success. PMID- 3328317 TI - Contemporary antihypertensive therapy. AB - Pharmacotherapy of human hypertension is effective, safe and well-tolerated. Antihypertensive drugs are of three broad classes: diuretics, sympatholytics and vasodilators. The use of each class is discussed and a summary of therapeutic considerations offered for representative agents. Recent trends in antihypertensive therapy are identified. PMID- 3328318 TI - A nineteenth century view of the optic commissure. AB - Historically, ophthalmologists and anatomists have been intrigued by the optic nerve and its decussation. Isaac Newton was the first to describe and suggest the significance of the chiasmal crossing, while W.H. Wollaston defined the importance of hemiretinal differentiation in 1824. However, at that time, the vertical meridian separating nasal from temporal retina was believed to be located at the optic papillae. This theory was disproved in 1870 by two Philadelphia ophthalmologists, who demonstrated and documented the vertical meridian at the macula during their examination of an injured Civil War soldier. PMID- 3328319 TI - Guidelines for the use of animals in biomedical research. PMID- 3328320 TI - Different prevalence of thromboembolism in the subtypes of congenital antithrombin III deficiency: review of 404 cases. PMID- 3328321 TI - Sample size in the planning and interpretation of clinical trials. AB - An understanding of sample size determination is important in both planning and interpreting the results of clinical trials. A Type II error occurs when it is concluded that there is no difference between treatment groups, when in truth there is a difference. Such a false negative conclusion results from too few patients in a trial. In this review the principles of estimating sample size before a trial is commenced and evaluating the results of a negative completed trial are reviewed. Clinically relevant examples are used to illustrate these concepts. PMID- 3328322 TI - Transitory decrease of platelet count, aggregation and adhesion after plasmapheresis and immunosorption procedures. PMID- 3328323 TI - [Single-dose treatment of lower urinary tract infections in women. A statistical summary of original studies]. PMID- 3328325 TI - Ultrastructural analysis of meiotic recombination and chiasma formation. AB - Meiotic recombination appears to be mediated by recombination nodules, small electron dense spheres, associated with the central region of the synaptonemal complex. These structures are a prerequisite for, not the result of crossing over and they undergo complex structural, numerical and distributional changes before the final distribution of crossovers is achieved. In the organisms studied the nodules are placed randomly along and among the bivalents at zygotene. Subsequently, the distribution is modified to insure that each bivalent and generally each bivalent arm attain a nodule and that close spacing of nodules is minimized. Analysis of the number and location of recombination nodules at pachytene provides knowledge of the number and physical distribution of crossovers in the individual bivalents. Chiasmata originate from recombination nodules. At early diplotene the chiasma consists of a retained segment of synaptonemal complex containing a derivative of a recombination nodule. At late meiotic prophase the segment is eliminated after the formation of a chromatin chiasma. PMID- 3328324 TI - Meiosis as a sexual dimorphic character of germinal cell differentiation. PMID- 3328327 TI - Natural infections of Wuchereria bancrofti in Aedes (Stegomyia) polynesiensis and Aedes (Finlaya) samoanus in Samoa. AB - Seven years after the 2nd mass treatment of the population with diethylcarbamazine, transmission of subperiodic Wuchereria bancrofti was studied in four villages in Samoa during one year by means of biting catches of Aedes polynesiensis and A. samoanus. 2 villages were coastal, one inland bush and the other an inland coconut plantation community. Overall infection and infective rates from 6702 Ae. polynesiensis were 0.84 and 0.27% respectively, and the infection rate from 2858 Ae. samoanus, collected in 10-minute catches from 24 sites, was 0.65%. No infective Ae. samoanus was found in these samples. 12-hour all-day catches in the 2 coastal villages confirmed active transmission by Ae. polynesiensis. 12-hour all-night catches in the same 2 villages recorded high transmission by Ae. samoanus although there was little evidence of local breeding. The annual transmission potential for Ae. polynesiensis and Ae. samoanus was high in one of the coastal villages and low in the other. A total of 221 infected Ae. polynesiensis and 40 Ae. samoanus were recorded. Of the 72 infective Ae. polynesiensis, 59.1% contained 1 to 2 larvae each (median density 1.4); 70% of the 40 infected Ae. samoanus had 1 to 2 larvae (median density 1.1). From the proportion of infective Ae. polynesiensis the mean probability of survival was estimated as 0.917. PMID- 3328326 TI - Cytochromes P-450 and the regulation of steroid synthesis. PMID- 3328328 TI - Distribution of vectors, transmission indices and microfilaria rates of subperiodic Wuchereria bancrofti in relation to village ecotypes in Samoa. AB - Aedes polynesiensis and Ae. samoanus biting densities and Wuchereria bancrofti infection and infective rates were studied in 47 villages throughout the islands of Samoa Upolu, Manono and Savaii during 1978-79, and microfilaria (mf) rates were surveyed in 28 of the villages. The mf rate was correlated with both infection and infective rates of Ae. polynesiensis in Upolu, but not of Ae. samoanus. In Upolu, Ae. polynesiensis was apparently the major vector. It was relatively more abundant in more cultivated and populated areas, along the northern coast of Upolu, except Apia town area. In Savaii, Ae. samoanus predominated over Ae. polynesiensis except in "plantation" villages. Relatively high biting densities and rates of infection and infectivity indicated that Ae. samoanus was not less important than Ae. polynesiensis as a vector in Savaii. Ae. samoanus preferred natural vegetation, in contrast to Ae. polynesiensis which was found near human habitations in cultivated land. There was no difference between the biting densities of Ae. polynesiensis in "coastal" and "inland" villages, indicating that crab holes (numerous only in some coastal villages) may not influence the density of Ae. polynesiensis. Higher mf rates were associated with villages where Ae. polynesiensis, rather than Ae. samoanus, was dominant, indicating that Ae. polynesiensis was generally a more efficient vector. In the former villages, the difference in mf rates between males and females was smaller than in the latter, probably reflecting a difference in biting habits of the vectors. Ae. polynesiensis infections were recorded in plantations over 2 km from any village, suggesting that both habitats were foci of transmission. PMID- 3328329 TI - Double-blind study to assess the efficacy of chlorproguanil given alone or in combination with chloroquine for malaria chemoprophylaxis in an area with Plasmodium falciparum resistance to chloroquine, pyrimethamine and cycloguanil. AB - In this study the efficacy of chlorproguanil (20 mg base weekly) was compared in schoolchildren with that of chloroquine (200 mg base weekly) and that of both drugs combined (20 mg base + 200 mg base weekly). The double blind trial was performed in the rice field area of the Ruzizi valley in Burundi, where Plasmodium falciparum is widely resistant to chloroquine, and where pyrimethamine resistance with cycloguanil cross-resistance had been demonstrated. After 17 weeks, when the trial was ended, 60% breakthroughs had been observed among the children taking chloroquine, 72% among those under chlorproguanil and 61% among those under chlorproguanil and chloroquine. In children weighing between 15 and 24 kg, the failure rate was significantly higher in those treated with chlorproguanil than in the group treated with chloroquine. No difference in efficacy was observed in children weighing 25 to 39 kg. There was no significant increase of efficacy when chlorproguanil was given in association with chloroquine. The mean titre of fluorescent antibodies was the same in each treated group on week 5 and week 15. The comparison of these data with the infection rates in non-protected children suggests that malaria could not be prevented with any of the drug regimens utilized in the study. PMID- 3328330 TI - Amodiaquine fails to cure chloroquine resistant Plasmodium falciparum in the Punjab. AB - We evaluated amodiaquine as a replacement drug for treating falciparum malaria in an area of Pakistani Punjab where chloroquine-resistant Plasmodium falciparum has recently emerged. Amodiaquine appeared to be 4 to 8 times more effective than chloroquine when P. falciparum isolates were tested in vitro. However, the recrudescence rate was greater than 50% after oral treatment with 20 mg/kg amodiaquine given over two successive days. This lack of therapeutic response from amodiaquine may have been due to selection of resistant parasites in the villages where the study was performed through extensive use of chloroquine for presumptive malaria treatment during the preceding 18 months. We conclude that amodiaquine is not a suitable replacement for chloroquine for treating falciparum malaria in our study area despite in vitro sensitivity data suggesting that it would be efficacious. Baseline in vitro sensitivity to mefloquine is also reported. PMID- 3328331 TI - Emergence of Plasmodium falciparum chloroquine resistance in the Sahel part of West Africa. PMID- 3328332 TI - In vitro response of Plasmodium falciparum to mefloquine in south-eastern Iran. PMID- 3328334 TI - Endemic malaria in four villages of the Pakistani province of Punjab. AB - The prevalence of malaria in 4 villages 60 km south of Lahore, Punjab, where Anopheles culicifacies is the vector was estimated from blood films made during three mass malaria surveys (MS) and at 204 clinics (CS) held over 18 consecutive months. The highest parasite rate occurred during October 1984 when 43% of the CS population had parasitaemias. Plasmodium vivax predominated early in the major transmission season (23% and 15% vivax parasitaemias in August 1983 and 1984 respectively) whereas P. falciparum was the most common species later in the transmission season (an average falciparum prevalence of 37% in October and November 1984) and following the transmission season through March. Despite the proximity and habitat similarity of the 4 villages, both total and species malaria prevalence rates showed inter-village differences. Asexual stage and gametocyte parasite rates in children were 2 to 5 times higher than in adults. No increased mortality due to malaria was detected among the 4000 study population. Malaria was stable and endemic, albeit seasonally transmitted, in these 4 villages during 1983 and 1984. PMID- 3328333 TI - Plasmodium vivax: isolation of mature asexual stages and gametocytes from infected human blood by colloidal silica (Percoll) gradient centrifugation. AB - The densities of human erythrocytes infected with P. vivax obtained from infected patients were determined by isopycnic centrifugation in continuous gradients of Percoll. The approximate densities of erythrocytes infected with rings were 1.086 to 1.1, trophozoites (amoeboid stages) 1.053 to 1.086, schizonts and gametocytes 1.053 to 1.056 and of the other cellular elements of blood, uninfected erythrocytes, 1.086 to 1.1, polymorphonuclear leucocytes 1.073 to 1.086 and mononuclear cells 1.062 to 1.073 g/ml. Based on these values, a one-step gradient of 47% Percoll was devised to separate erythrocytes infected with the more mature stages (trophozoites, schizonts and gametocytes) from uninfected erythrocytes. By this method it is possible to obtain parasitaemias of 88% to 98% from blood with starting parasitaemias of less than 0.7%. This method is therefore being routinely used for immunological, biochemical and molecular biological studies on P. vivax. PMID- 3328335 TI - Pseudomonas aeruginosa septicaemia in a patient with severe Plasmodium falciparum. AB - This report describes a Danish patient with severe Plasmodium falciparum infection and Pseudomonas aeruginosa septicaemia. The patient had been sailing along the coast of West Africa for ten years without taking any antimalaria prophylaxis and without any apparent previous history of malaria. He presented with severe form of malaria, progressing rapidly into coma and died within a short time. P. aeruginosa was isolated from his blood taken on the day of admission. His neutrophils were all occupied by P. falciparum. The unusual combination of severe falciparum malaria infection and P. aeruginosa septicaemia with extensive involvement of neutrophils lends further support for the role of phagocytic defence in malaria. PMID- 3328336 TI - Reduction in erythrocytic GSH level and stability in Plasmodium vivax malaria. AB - The existence of haemolytic anaemia in malaria indicates disturbances in red cell stability due to physical as well as metabolic stress attributable to the malarial parasite. As erythrocytic reduced glutathione (GSH) is involved in maintaining the integrity of red cells, the status of erythrocytic GSH was studied in 40 patients infected with Plasmodium vivax before and after therapy with chloroquine. 40 normal subjects, age- and sex-matched, were studied as controls. The level of erythrocytic GSH of malaria patients during infection and before therapy was significantly lower in comparison with controls (P less than 0.0005). Instability of GSH was recorded in 17 of 40 patients, while none of the controls showed such a defect. There was a progressive decrease in GSH level and stability of the host red cells with increasing parasitaemia. Normal values were obtained following therapy and cure of malaria indicating that the changes in GSH level and stability are induced by P. vivax. Alterations in the GSH metabolism may represent one of the factors contributing to the severity of anaemia in malaria due to P. vivax infection. PMID- 3328337 TI - Detection of homologous and heterologous malaria antibodies by application of Plasmodium falciparum merozoite antigen to an ELISA. AB - Sera of patients with anti-plasmodial antibodies determined by indirect fluorescence antibody test (IFAT) were used to evaluate an enzyme immunoassay (IgG ELISA) for determining antibodies to Plasmodium falciparum merozoite antigen. The two tests correlated well. Antibodies to species other than P. falciparum, however, were detected by P. falciparum merozoite antigen to a limited extent only. PMID- 3328338 TI - Insulin-dependent ketosis-resistant diabetes in Ethiopia. AB - Anthropometric, clinical and biochemical findings were compared in 30 rural (group A), 18 urban insulin-requiring (group B) and 45 urban oral-agent responsive (group C) newly diagnosed diabetics. Mean ages at onset were 28.3 +/- 12.0, 25.6 +/- 14.5 and 42.1 +/- 10.5 years respectively. The differences between A and C and between B and C were significant. Group A were poor and malnourished, with body mass index (BMI) 15.9 +/- 1.9 and 17.2 +/- 3.7 kg/m2 for males and females respectively, presented with a long history of classical diabetes without ketoacidosis and required insulin in modest doses. 3 of 10 cases had excess stool fat but none of 13 unselected cases had pancreatic calcification. Group C were better nourished, with BMI 22.6 +/- 2.8 and 22.4 +/- 4.5 kg/m2, and responded to oral agents. Group B, with BMI 17.2 +/- 2.6 and 18.6 +/- 3.1 kg/m2, required insulin for control but had C-peptide levels above 0.02 nmol/1 in 10 of 15 cases. Anthropometric indices for males, but not for females, were significantly lower in group A than in group B or C. There were significant differences in levels of glucose between A and B and A and C, free fatty acids between A and C and B and C, insulin between A and B and A and C and C-peptide between A and C and B and C. Of the 3 groups the rural type most closely resembled the tropical variants. PMID- 3328339 TI - Differential clinical features and stool findings in shigellosis and amoebic dysentery. AB - To obtain information that could assist the clinician to differentiate between shigellosis and amoebic dysentery, we compared clinical features and stool findings in 58 adult male patients in Bangladesh. Mean values indicated that patients with invasive amoebiasis were older and had a longer prehospital illness, a lower body weight, less frequent fever, a lower haematocrit and a higher white blood cell count than patients with shigellosis. The mean number of faecal leucocytes per mm3 was significantly higher in shigellosis than in amoebiasis (28,700 vs 10,300) and correlated with the estimated number of faecal leucocytes per microscopic high power field in a wet mount preparation. Patients with shigellosis more often had over 50 white blood cells per high power field. Although the mean stool pH in amoebiasis was lower than in shigellosis (6.26 vs 6.60), the difference was not statistically significant. Concentrations of stool electrolytes did not differ between the two diseases. These findings indicate that age, duration of illness, the presence of fever and the number of faecal leucocytes may help to differentiate between shigellosis and amoebic dysentery. PMID- 3328340 TI - The aetiology of diarrhoea in a farming community in Zimbabwe. AB - A survey of enteric pathogens in 143 children with diarrhoea, 116 age-matched controls and 524 asymptomatic people of all ages in a commercial farming area was carried out over a period of one year. Giardia lamblia was detected in 34% of the cases, 29% of the controls and 23% of asymptomatic people of all ages. Various bacterial pathogens (Campylobacter, Shigella, Salmonella and enteropathogenic Escherichia coli) were isolated from 23% of the cases and 15% of the controls. Enteropathogenic E. coli was isolated as frequently from the cases as from the controls and asymptomatic people of all ages. PMID- 3328341 TI - The effect of combinations of qinghaosu (artemisinin) with standard antimalarial drugs in the suppressive treatment of malaria in mice. AB - Artemisinin is a novel antimalarial drug isolated in China from the wormwood plant Artemisia annua L. Studies with rodent malaria were carried out to detect antagonism and synergism with a variety of antimalarial drugs. Isobolograms of drug interaction were plotted at the ED90 level. With a normally susceptible strain of Plasmodium berghei, marked potentiative synergism was found with mefloquine, tetracycline and spiramycin. There was some synergism also with primaquine. Combinations of artemisinin with dapsone, sulfadiazine, sulfadoxine, pyrimethamine, pyrimethamine/sulfadoxine and cycloguanil showed antagonism. A high degree of potentiation was shown between artemisinin and primaquine with a primaquine-resistant strain, whilst the combination with mefloquine showed enhanced potentiation with a mefloquine-resistant strain. Combinations of artemisinin with mefloquine, primaquine, tetracycline or clindamycin showed marked potentiation with an artemisinin-resistant strain. The mechanisms underlying the drug interactions observed are discussed. PMID- 3328342 TI - A controlled clinical trial of artemether (qinghaosu derivative) versus quinine in complicated and severe falciparum malaria. AB - 31 pairs of patients with complicated falciparum malaria (with anaemia, jaundice, raised blood urea, hyperpyrexia or more than 2% of erythrocytes parasitized) were treated with artemether or quinine. All patients in the artemether group survived but 2 of those treated with quinine died. Fever clearance time and parasite clearance time of patients treated with artemether were significantly shorter than in the quinine-treated group. One patient who failed to respond to quinine within 72 h was saved with artemether. Follow-up of the patients showed that 9 of 23 (39.1%) recrudesced on day 28 in the artemether group. In the quinine group the recrudescence rate was 9% (2 of 22). Hence artemether may be considered as one of the drugs of choice for severely ill patients; it may even be better than quinine. PMID- 3328343 TI - A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children. AB - A trial was undertaken in a rural area of The Gambia to investigate the impact of permethrin-treated bed nets on malaria. Two groups of children, matched for age, sex, and malaria exposure, were followed through the rainy season of 1985 for illness and febrile episodes. One group of 205 children slept under permethrin treated bed nets (0.5 g/m2); 184 children who slept under placebo-treated nets formed the control group. At the end of the rains the children were examined for splenomegaly and blood samples were taken for determination of packed cell volume (PCV) and parasitaemia. Permethrin treatment of bed nets was well accepted and was without side-effects. Children who slept under treated nets had significantly fewer episodes of clinical malaria than control children. However, at the end of the rains there was no significant difference in the prevalence of splenomegaly or parasitaemia or in the mean PCV between the groups. It is suggested that permethrin treatment of nets may have a greater effect on the duration of probing by mosquitoes for a blood meal than on the number of bites received. PMID- 3328344 TI - Inhibition of intra-erythrocytic growth of Plasmodium falciparum by human sera from Papua New Guinea. AB - Plasmodium falciparum was cultured through a single intra-erythrocytic cycle of growth in the presence of sera from various areas of Papua New Guinea. Of 194 sera tested from healthy individuals or subjects with hyperreactive malarious splenomegaly (HMS), 107 (55%) significantly inhibited parasite development. Inhibition did not correlate with malaria experience or HMS, though it was to some extent a seasonal phenomenon. Sera with inhibitory activity lost this after dialysis. A possible explanation for these findings is the occurrence of a dietary toxin with antimalarial properties detectable in vitro. PMID- 3328345 TI - Ahaptoglobinaemia in Melanesia: DNA and malarial antibody studies. AB - To assess the relative contributions of genetic and acquired factors, particularly malaria, to the high frequencies of ahaptoglobinaemia found in Melanesia we have performed DNA and malarial antibody studies in a population from Vanuatu. No gene deletion or rearrangement was found on gene mapping in any ahaptoglobinaemic individual and the frequencies of the Hp1 and Hp2 alleles in the ahaptoglobinaemic group were similar to controls. However, antibodies to Plasmodium falciparum were significantly elevated in the ahaptoglobinaemics. These data suggest that malaria rather than genetic factors is the major cause of ahaptoglobinaemia in Melanesia. PMID- 3328346 TI - Evaluation of a newly developed direct agglutination test (DAT) for serodiagnosis and sero-epidemiological studies of visceral leishmaniasis: comparison with IFAT and ELISA. AB - A newly developed direct agglutination test (DAT) for visceral leishmaniasis, IFAT and ELISA were applied to sera of patients with visceral leishmaniasis, African and American trypanosomiasis, other parasitic infections and healthy controls. The sensitivities of the 3 tests were comparable (96.3% to 100%); excluding patients with African and American trypanosomiasis, the specificities of DAT and IFAT were 100% and ELISA 87.3%. When trypanosomiasis sera were included, the specificities were 72.6%, 94.3% and 79.4% in DAT, IFAT and ELISA respectively. In 273 sera from a leishmaniasis endemic area (Baringo District, Kenya), the sensitivity was 80% in DAT and IFAT and 60% in ELISA, specificities being 99.6% (DAT), 98.5% (IFAT) and 62.5% (ELISA). As the new DAT is economical and easy to perform, it is recommended for sero-epidemiological field work on visceral leishmaniasis. PMID- 3328347 TI - Comparison between bloodstream and procyclic form trypanosomes for serological diagnosis of African human trypanosomiasis. AB - Trypanosoma brucei brucei MiTat 1.2 bloodstream and corresponding procyclic forms, as well as procyclics of T. b. gambiense and T. b. rhodesiense, were fixed, in suspension, using a mixture of 80% acetone and 0.25% (v/v) formalin in saline and used as antigens for diagnosis of African human trypanosomiasis by the indirect immunofluorescent antibody test. T. b. brucei bloodstream forms detected 41/42 and 37/41 parasitologically diagnosed cases of T. b. rhodesiense and T. b. gambiense trypanosomiasis, respectively, while the procyclic stages detected the same number (41/42) of T. b. rhodesiense, but fewer (29/41) T. b. gambiense infections. PMID- 3328348 TI - First record of Trypanosoma (Schizotrypanum) cruzi from the western Amazon basin, Caqueta, Colombia. PMID- 3328349 TI - Bancroftian filariasis in coastal north Trinidad: the effects of mass chemotherapy using spaced doses of diethylcarbamazine citrate on human microfilaraemias and vector infection rates. AB - The effects of a mass chemotherapy programme using spaced doses of diethylcarbamazine citrate on Wuchereria bancrofti microfilaraemias and vector infection rates were studied in an isolated rural community of 650 people in north Trinidad where a microfilaria rate of 15% had previously been recorded. A single oral dose of 6 mg/kg body weight was given at monthly intervals for one year. After 6 months, 79% (52/66) of persons previously microfilaraemic had become negative. After 12 months the negative proportion had increased to 90% (63/70). The geometric mean microfilaria density of those still microfilaraemic was reduced from 19.7 to 4.6 per 100 mm3 of blood. Of 147 initially negative persons, none had become positive following treatment. Filarial infection rates in Culex quinquefasciatus from randomly sampled houses fell from 6.4% to zero; in houses where occupants with microfilaraemia had been identified before treatment, the rate was reduced from 15.8% to zero. In a supplementary study, however, weekly collections from one initially positive house showed a rapid decline in the vector infection rate from 43% to 2% after three months but an additional 3 months elapsed before the index reached zero. There was negligible microfilarial uptake by the vectors from residual low-density microfilaraemias (less than 10 microfilariae per 100 mm3 of blood) after chemotherapy. PMID- 3328350 TI - [Development of cytological research in the Ukrainian SSR]. PMID- 3328351 TI - [Development of medical genetics in the Ukraine: successes and tasks]. PMID- 3328353 TI - [Suturing of the menisci and arthroscopic evaluation]. PMID- 3328352 TI - [Mutagenic action of latex polymerization stabilizers in various test systems]. AB - The cytogenetic activity of latex polymerization stabilizers (monoethanolamine, triethanolamine and neozon-D) is investigated in three different test systems. It is shown that monoethanolamine and triethanolamine are weak inductors of chromosome breaks in the culture of human lymphocytes and in the Crepis capillaris seeds and induce low levels of gene mutations in the Ames systems. The third stabilizer--neozon-D manifests higher mutagenic activity and definite cytotoxic effect. Monoethanolamine and triethanolamine as to their weak mutagenic effect are recommended as preferable stabilizers to be used in the latex industry. PMID- 3328355 TI - [Diabetic neuropathy: theories on its metabolic pathogenesis]. PMID- 3328354 TI - [Verapamil poisoning. A case with fatal course and literature review]. PMID- 3328356 TI - [The diagnosis of vaginitis in general practice]. PMID- 3328358 TI - [Borderline tumor of the ovary. II. Pathology, treatment and prognosis]. PMID- 3328357 TI - [Borderline tumor of the ovary. I. History, classification, anamnesis and etiology]. PMID- 3328359 TI - [Ovarian cancer--potential risk factors]. PMID- 3328360 TI - [Diet, nutritional status and ovarian cancer--is there a connection?]. PMID- 3328361 TI - [Ovarian cancer in Denmark 1943-1982]. PMID- 3328362 TI - Death rates from diabetes mellitus in Ireland 1833-1983: a historical commentary. AB - A world-wide increase in diabetic deaths and a varying rate of increase between one country and another over the past hundred years has long been recognised. During the nineteenth century, the incidence of diabetes was low in Ireland as measured by mortality. Nevertheless, the rising trend found elsewhere was also apparent in Ireland. Recorded deaths were 0.22/100,000 of the population in 1840, rising to 13.2 by 1972. Most of the increase occurred between the 1880s and 1911, but only 15% of this can be accounted for by an ageing population. It is, therefore, necessary to seek other explanations. During the period, sugar and fat consumption in Ireland rose sharply. It has not been possible precisely to relate dietary causes to the incidence of diabetes, but the Irish experience suggests that such a link may exist. PMID- 3328363 TI - Salmonella in a chicken hatchery. PMID- 3328364 TI - External fixation in contemporary fracture management. AB - Important advances have been made within the last two decades in the field of fracture management. The development of the AO internal fixation system and the advances in cast bracing techniques are but two of the improvements worthy of mention. It is, however, in the field of external fixation of fractures that the greatest advances have been made. This paper traces the history of external fixation up to the present day and discusses, with examples, the application of external fixation in the management of complex limb fractures. PMID- 3328365 TI - Sesquicentenary of the Belfast Medical School. Symposium to mark the 150th anniversary of the foundation of the Medical School in Belfast. 16 May 1986. PMID- 3328366 TI - The personalities and problems of 60 years ago. PMID- 3328368 TI - The early medical school: foundation and first crisis--the 'college hospital' affair. PMID- 3328367 TI - The 'wild geese'. PMID- 3328369 TI - The Ulster Hospital--a short history. PMID- 3328370 TI - The Mater Infirmorum Hospital. PMID- 3328371 TI - A view from the United States. PMID- 3328373 TI - Anaesthetics. With special reference to Ivan Magill. PMID- 3328374 TI - Advances in the treatment of trauma. PMID- 3328372 TI - Transplantation. PMID- 3328375 TI - The pre-clinical departments. PMID- 3328377 TI - Relation between criteria: case-finding method and prevalence. AB - In order to test some hypothesis of possible causes of different figures of prevalence reported for especially mild mental retardation ten Scandinavian studies 1961-1986 are reviewed, compared and critically analyzed. Theoretical definitions of mental retardation in these studies are found to correspond well. The operational procedures and measures used, in contrast, are much more heterogeneous and still more so the case-finding methods: sampling, screening or other identification procedures. It is concluded that case-finding methods are the most decisive factors for the resulting prevalence figures in epidemiological studies, especially concerning mild mental retardation. In an analogous way numbers of persons identified as mentally retarded within the special services (administratively classified by BPSMR) in different countries are determined by criteria for inclusion and social processes of different kinds. PMID- 3328376 TI - Aspects on the prevention of mental handicap associated with intrauterine growth retardation. PMID- 3328378 TI - The mental age deficit: explanation and treatment. AB - Mildly and moderately retarded persons perform in many psychological tasks, by definition, at lower levels than do nonretarded persons of equal chronological age (CA), but they also perform often at lower levels than do younger nonretarded persons of equal mental age (MA). "MA deficit" appears to derive in large part from experience, especially in four domains: (a) behavioral incompetence; (b) deficient cognitive structures, including the special case of communicative incompetence; (c) relative task-extrinsic motivational orientation; (d) negative social ecology, i.e., unproductive person-setting matches. The very experience of being retarded makes one more so. Treatment designed at least to overcome the MA deficit should be focused on these domains. PMID- 3328379 TI - Aspects of prenatal prevention. AB - There has been strong progress in the field of prenatal prevention during the last decade. New technical advances have made it possible to diagnose new disorders prenatally and in the near future intrauterine treatment will become feasible for some of them. PMID- 3328380 TI - Traditional views and new perspectives on the genetics of mild mental retardation. AB - Normal intelligence and mild mental retardation are generally assumed to be determined by additive polygenes. This old and basic theory is challenged by findings from modern population studies. The discrepancies concern frequency of mild mental retardation, sex ratio, and additional somatic handicaps in populations with mild mental retardation. PMID- 3328381 TI - Sex differences in the classification of children as mildly mentally retarded. AB - A consistent finding in epidemiological studies of mild mental retardation (MMR) is a somewhat higher prevalence of boys than girls. Our own study in Aberdeen agreed with these findings. Examination of the numbers of boys and girls at different levels of retardation within our study population revealed the greatest excess at the highest IQ levels of greater than or equal to 75. This was found to be true in other studies as well. Since this IQ range is above the generally agreed upon cut-off point used to classify children as MMR, these findings suggest that boys remaining in regular classes may be having more difficulty in school performance than girls. Possible reasons for this are examined. PMID- 3328382 TI - Ultrasonography for fetal weight estimation: the Birnholz equation. AB - In the population of 563 normal live births, subject to the selection criteria of this study, the mean ultrasonographically-estimated fetal weight calculated using the Birnholz equation accurately predicts the mean true birth weight with less than 1 percent error. However, on a pairwise basis, the error was found to be systematic (rather than random) with a large standard error of the estimate (+/- 300 g). The equation consistently underestimated the mean birth weight between 1500-3750 g and consistently overestimated it thereafter. PMID- 3328383 TI - [Ocular hypotensive effect of low doses of timolol]. PMID- 3328384 TI - [Initial experience with endocapsular fixation of intraocular lenses with their attachment to the anterior capsule of the lens]. PMID- 3328385 TI - [Ophthalmological manifestations of the side effects of cardiovascular drugs]. PMID- 3328387 TI - [Combined microsurgical forceps for joining the edges of the operative wound of the fibrous capsule of the eye]. PMID- 3328386 TI - [A case of long-term presence of caterpillar hairs in the eye]. PMID- 3328388 TI - Fleas and related disease. AB - This article considers the clinical signs of flea allergy dermatitis, and the diagnosis and general principles of flea control for the pet and its environment. PMID- 3328389 TI - Mites and related disease. AB - Parasitic mites cause a variety of dermatoses in domestic animals. The clinical signs, diagnosis, and treatment of canine and feline demodicosis, canine scabies, notoedric mange, cheyletiellosis, otodectic mange, and other mite infestations are discussed. PMID- 3328390 TI - Tapeworms. AB - Dogs and cats become infected with tapeworms by ingesting intermediate hosts that contain encysted juvenile tapeworms called larvae. The dog or cat is said to be the definitive host because it shelters the sexually reproductive, egg-producing stage of the tapeworm. The intermediate hosts, which are vertebrates in the case of Taenia and Mesocestoides and insects in the case of Dipylidium and Hymenolepis, become infected by ingesting unhatched but infective tapeworm eggs discharged in the feces of the dog or cat. The relatively less common Diphyllobothrium and Spirometra tapeworms discharge eggs that are undeveloped when passed in the feces and must fall into water to undergo development to the coracidium stage. Diphyllobothrium and Spirometra may have two or three aquatic intermediate hosts in series. The first of these, a copepod, ingests the free swimming coracidium or ciliated oncosphere that has hatched from the egg. The final intermediate host containing the larva (plerocercoid) infective for the dog or cat is an aquatic vertebrate (fish, frog, water snake). Thus, dogs and cats become infected with tapeworms by eating uncooked meat or fish or by ingesting certain insects. These intermediate hosts are infected with juvenile tapeworms called larvae, which are the infective form for the dog or cat. The intermediate hosts, in turn, become infected by ingesting tapeworm eggs discharged in the feces of the dog or cat or, in the case of Diphyllobothrium and Spirometra, by ingesting coracidia that have subsequently developed in and hatched from such eggs. By far the most common tapeworms of dogs and cats in North America are D. caninum, T. pisiformis, and T. hydatigena. Therefore, the most common sources of tapeworm infection are, respectively, fleas, wild rabbits, and the uncooked meat and offal of ruminants and swine. Whenever a dose of tapeworm remedy is administered or dispensed, the client should be informed of these potential sources of reinfection. There is considerable overlap in the spectra of activity of currently available cestocides. Mebendazole, fenbendazole, niclosamide, bunamidine, and praziquantel are all effective against Taenia spp. Bunamidine is the drug of choice against Spirometra, Diphyllobothrium, and Mesocestoides. Praziquantel is the drug of choice against Echinococcus and Dipylidium. PMID- 3328391 TI - Ascarid infections of cats and dogs. AB - The ascarids Toxocara canis, Toxocara cati, and Toxascaris leonina are probably the most common gastrointestinal helminths encountered in small animal practice. Both T. canis and T. cati can cause serious disease in kittens and puppies; T. leonina is generally less pathogenic. Prenatal transmission assures that virtually all puppies are born infected with T. canis. Transmammary transmission is probably the major route of infection for kittens with T. cati. In addition, all three species of worm produce resistant eggs and use paratenic hosts to facilitate transmission. Much is now known about the complex biology and life history of T. canis. However, many questions, such as those concerning the mechanisms of larval survival within host tissues and of larval reactivation and migration during pregnancy, await further study. The mechanism of resistance to ascarid infections in cats and dogs has not been clearly defined. Ascariasis is traditionally thought to be a disease of young animals, with older animals being considered immune. However, at least in the case of T. canis, adult dogs can be repeatedly infected. A wide range of anthelmintics is available with extremely high efficacy against patent ascarid infections. The problem of prenatal infection with T. canis may be overcome by strategic use of the newer benzimidazole-carbamates, and the production of ascarid-free puppies now seems possible. However, complete larvicidal activity against somatic stages has not been convincingly demonstrated. Visceral larva migrans-like syndromes are now being recognized in dogs and cats. In addition, visceral larva migrans in children due to T. canis continues to be a significant zoonotic disease in North America and underscores the need for the veterinary profession to control ascarid infections in cats and dogs at every opportunity. PMID- 3328392 TI - Hookworms of dogs and cats. AB - Hookworms are probably the most faithful intestinal parasites of dogs and cats. Infecting all ages, they are life-threatening to the very young and potentially so to the fully mature hookworm-resistant host. Discussed in this article are the diagnosis of hookworm infection, the life cycle of hookworms, the cutaneous and intestinal manifestations of hookworm infection and disease, and the treatment and prevention of infection. PMID- 3328393 TI - Whipworms and intestinal threadworms. AB - Whipworms (genus Trichuris) parasitize the lower bowel of humans, domestic animals, and wild animals. The species of Trichuris that are important in small animal practice are T. vulpis in the dog and T. campanula and T. serrata in the cat. Intestinal threadworms (Strongyloides stercoralis in the dog and S. tumefaciens in the cat) parasitize the small intestine. The identification of whipworms and threadworms, their life cycles, and the diagnosis, treatment, and control of infection are discussed in this article. PMID- 3328394 TI - Giardiasis. AB - Giardia spp. are common, yet frequently overlooked, parasites of small animals. These parasites may cause chronic diarrhea in dogs and cats. This article discusses the clinical signs of giardiasis, and its diagnosis, treatment, and control. PMID- 3328395 TI - Toxoplasmosis. AB - Toxoplasma gondii is a protozoan parasite that infects most species of warm blooded animals, including human beings. Infection in cats is of particular interest because Felidae (domestic and wild) are the only known definitive hosts for T. gondii and thus are the main reservoirs of infection. Clinical and public health aspects of T. gondii infections in cats and dogs are discussed in this article. PMID- 3328396 TI - Parasites of the respiratory tract. AB - The author discusses the parasites that infect the nasal passages, trachea, bronchi, and lung parenchyma of dogs and cats. The clinical signs, diagnosis, epidemiology, treatment, and control of infection are also considered. PMID- 3328398 TI - Heartworm infection. AB - Dirofilaria immitis is an epizootic filarial parasite that most often infects domestic dogs. This article provides information about the life cycle of Dirofilaria immitis as well as the epidemiology, diagnosis, clinical signs, and treatment of heartworm infection. PMID- 3328397 TI - Erythrocytic rickettsia and protozoa of the dog and cat. AB - This article summarizes the biologic and clinical features of the rickettsia and protozoa of canine and feline erythrocytes that are significant in North America: Haemobartonella canis, Haemobartonella felis, Cytauxzoon felis, Babesia canis, and Babesia gibsoni. PMID- 3328400 TI - [Current concepts of bone remodeling and their significance in x-ray diagnosis]. PMID- 3328399 TI - Vitamin E. AB - Vitamin E activity was first identified as a dietary factor essential for reproduction in the rat. It is now known that this vitamin has a far wider range of functions in the body than its role in fertility. It interacts with selenium containing glutathione peroxidase to prevent the oxidative breakdown of tissue membranes associated with the hydroperoxides of polyunsaturated fatty acids. Relationships with other factors such as stress and vitamin C, have been proposed. The symptoms of deficiency of vitamin E vary according to species. With so many variables it is difficult to estimate the optimum allowances of the vitamin for the many types of livestock diets. These problems are discussed and the calculation of allowances of vitamin E in rations for both monogastric and ruminant animals is explained. PMID- 3328401 TI - Fever, anorexia and forestomach hypomotility in ruminants. AB - Acute febrile diseases are characterized by specific and non-specific symptoms. The non-specific responses include among other signs fever, dullness, anorexia and changes in gastric function. It is the purpose of this review to describe present concepts of fever and the associated reactions produced by bacterial pyrogens and the mechanisms of those reactions. The available data indicate that interleukin-1 is a key mediator of host responses to bacterial infections. However, many questions have not yet been clearly answered. In particular, more detailed studies of the processes within the CNS responsible for anorexia are still required. PMID- 3328403 TI - [Folk medicine manuscript books. Their general characteristics]. PMID- 3328402 TI - A review of new approaches to assessing hepatic function in animals. AB - Although a multitude of effective liver function tests are available for use in animals, a variety of modifications of currently used tests have been recently reported. In addition, newer procedures now used in human medicine may also provide unique insights into assessing and detecting acquired hepatic disorders in animals. Examples of new procedures are: assessing microsomal mixed function oxidase activity by plasma caffeine clearance; estimating the extent of active hepatic fibrogenesis through serum procollagen-III peptide levels; determining hepatic blood flow and functional mass by the galactose elimination capacity; detecting primary hepatocellular cancer through serum or urinary ligandin levels; and to estimate the liver's maximal capacity to excrete indocyanine green independent of blood flow. In evaluating drugs as to their hepatotoxicity, function tests should be included in the liver profile which measure specific metabolic alterations unique to the compound under study. PMID- 3328406 TI - [Incidence of symptomless kidney diseases in ultrasonography studies]. PMID- 3328404 TI - [Arterial vessels of the kidney in domestic swine]. AB - By histological preparation, measuring, corrosion and angiography were studied the arterial blood vessels of 120 kidneys from 60 individuals at different ages. It was established that the kidney artery in the most cases (70%) divides by the dichotomous type in cranial and caudal or in dorsal and ventral branches, and rarely (30%) by the disseminated type in 3 branches--two cranial and one caudal. Investigated were the position, course and branching of the prelobar, interlobar, the arcuate, the inter- and intra-lobular arteries. PMID- 3328405 TI - Proprioceptive knowledge of eye position. AB - The peripheral and central apparatus for extraretinal (non-visual) sensing of eye position by proprioception (inflow) is documented. The functional significance of this inflowing signal is shown by its role in (1) providing oculomotor stability in fixation and conjugacy, (2) specification of visual direction, (3) development of some visual functions, and (4) depth and vergence responses. Inflow is seen as a slowly-operating calibrator of eye position, with outflow signals read out from the underlying inflow signal. Good "preparations" for studying inflow include humans having their extraocular muscles surgically manipulated in some way for treatment, or those with some deficit in the afferent pathways. A complete understanding of the oculomotor system, in normal and pathological conditions, demands the inclusion of inflow. PMID- 3328407 TI - [Hypertension, the present status of therapy and prevention throughout the world]. PMID- 3328408 TI - [Combination injury caused by sarin and gamma irradiation]. PMID- 3328409 TI - [State of nonspecific resistance of the body in patients with reactive arthritis as affected by whole-body UV radiation]. PMID- 3328410 TI - [Physical factors in the combination therapy of patients with ureteral calculi]. PMID- 3328411 TI - [Clinico-pathophysiological aspects of low-frequency impulse electrotherapy of chronic nonspecific salpingo-oophoritis]. PMID- 3328412 TI - [Biochemical and regulatory aspects of the function of ketone bodies in the body (review of the literature)]. PMID- 3328413 TI - [Effect of proliferation-stimulating factors on cholesterol esterification in the serum of rats with acute tetrachloromethane poisoning]. AB - Three phases of cholesterolemia were detected in rats after single administration of CCl4 at a dose of 0.3 ml of oil solution per 100 g of body mass. Factors, stimulating proliferation of hepatocytes and isolated from regenerating liver tissue, did not affect the type of cholesterolemia whereas they stimulated cholesterol esters formation in circulation. PMID- 3328414 TI - [Physiological role and clinical significance of 3-methoxy-4 hydroxyethyleneglycol, a noradrenaline metabolite (review of the literature)]. AB - Biochemical pathways of noradrenaline conversion into free and bound forms of 3 methoxy-4-hydroxyphenyl ethyleneglycol (MOPEG) in central and peripheral noradrenergic neurones, content of free and bound forms of MOPEG in various biological fluids as well as relative amount of the substance in central and peripheral pools and, at last, clinical importance of the noradrenaline metabolite study are reviewed. The first part of the review considers the experimental data of noradrenaline metabolism in animal brain, the second and third parts deal with experimental and clinical studies of content, role and importance of MOPEG in a human body. Perspectives of MOPEG studies for diagnostic purposes as well as for the more accurate analysis of catecholamine metabolism and of sympathoadrenal system functional state under clinical and experimental conditions are considered. PMID- 3328417 TI - [Study of the problem of parkinsonism and aging (review of the literature)]. PMID- 3328416 TI - [Functional disorders of the insular system of the pancreas in middle-aged and elderly patients with pulmonary tuberculosis]. PMID- 3328415 TI - [Drug interactions in middle-aged and elderly patients (review of the literature)]. PMID- 3328418 TI - [The role of the mycotic carrier state in the development of manifest forms of fungal foot infection]. PMID- 3328421 TI - [Detection of the rabies virus in the brain and salivary glands of animals by using an immunoenzyme method]. PMID- 3328422 TI - [The action of trimetazidine (TMZ)]. PMID- 3328419 TI - [Viktor Mikhailovich Zhdanov]. PMID- 3328423 TI - [Favorable effect of peritoneal dialysis in a patient with bacterial endocarditis complicated by renal failure and congestive circulatory failure]. PMID- 3328420 TI - [Genome structure and gene expression of the human immunodeficiency virus (a review of the foreign literature)]. PMID- 3328424 TI - [Vitamin A and neoplasms]. PMID- 3328425 TI - [Hemorrhage as a complication of Salmonella infection]. PMID- 3328426 TI - [Intrarenal manometry of transplanted kidneys]. PMID- 3328427 TI - [Molsidomine in the treatment of ischemic heart disease]. PMID- 3328428 TI - [Fibrinogen: physiological and pathological aspects]. PMID- 3328429 TI - [The Great October Socialist Revolution and health politics]. PMID- 3328430 TI - [Effects of oral contraceptives on liver function and structure]. PMID- 3328431 TI - [The status of prenatal diagnosis of abnormalities at the Berlin Gynecologic University Clinic]. PMID- 3328432 TI - [Possible aerogenic pathogen transmission in surgery]. PMID- 3328433 TI - [A. R. Luria (1902-1977) and the neurosciences]. PMID- 3328435 TI - [Status of "blood coagulation active human citrate plasma" within the scope of blood component therapy]. PMID- 3328434 TI - [Angiotensin-converting enzyme inhibition--new methods in the treatment of arterial hypertension and heart failure]. PMID- 3328436 TI - [Possibilities and trends in the development of new sensitizers for photodynamic therapy and fluorescence diagnosis of tumors]. AB - The Photodynamic Therapy (PDT) is a new method in the treatment of tumors, which is highly effective in early stages of cancers. The efficacy of the therapy is mostly determined by the properties of the sensitizer used. On the basis of biophysical investigations and determination of photophysical parameters it is possible to suggest new potential photosensitizers. This approach allows a systematical research for new and more effective photosensitizers. PMID- 3328437 TI - [Current therapy of chronic arterial occlusive diseases of the lower extremities]. AB - Angiologists, vascular surgeons, and angiographers inform about the actual state of the therapy of the arterial occlusive diseases of the legs. The degree I of therapy comprises the conservative treatment for the improvement of the macrocirculation and the normalisation of the disturbed microcirculation, taking into particular consideration the therapy with antiviscositant drugs. The main chapter ends with the possibilities of the influence on the arteriosclerotic vascular processes as well as with the necessary rehabilitative measures. In the paragraph about the degree II of therapy the indications, contraindications, methods and results of the isolated and combined percutaneous transluminal angioplasty, the systemic and local fibrinolysis as well as the reconstructive vascular operations are represented. PMID- 3328438 TI - [Some new biochemical knowledge on the effect of nutritional factors on brain function]. AB - A survey is given of the importance of the sufficient supply of the brain with amino acids, with glucose, fatty substances (in particular with linoleic acid), with vitamins (A, E, B1, B2, B6, nicotinamide, choline, B12), with mineral substances and with trace elements (in particular with Fe, Zn, and Cu), taking into particular consideration findings of animal experiments. The transport capacity for the transfer of the substrates and essential nutritional factors into the nerve cells is different. In a high activity the formation of noradrenaline, of acetyl choline and of serotonin is in certain nerve cells influenced by the size of the uptake of the molecules necessary for this. By a protein-rich nutrition the formation of the noradrenaline and acetyl choline which are important for the maintenance of the waking state, by a carbohydrate rich diet the formation of the serotonin which is among others important for the evocation of sleep are furthered. PMID- 3328439 TI - [50 years of Garz theses]. AB - 50 years after the publication of the Garz theses by Gerhardt Katsch is tested what remains even nowadays still actual for the treatment of diabetics from the previous concept. It can be stated that the largest part of the then therapeutic recommendations since that time has frequently stood the test in practice and is in force still at present. This is of importance above all for the dietary regulations. - The Garz dietary prescriptions from 1930 to 1954 are summarizingly described here for the first time. They confirm the advantages of a fat restriction in the diabetes diet which are in general acknowledged at present. PMID- 3328440 TI - Innervation of the smooth muscle in human large intestine during ontogenesis. PMID- 3328441 TI - [Progress in the development of immunoenzyme assays]. PMID- 3328442 TI - [Computerized methods in the diagnosis and assessment of the efficacy of the surgical treatment of heart arrhythmias]. PMID- 3328443 TI - Storage methods for the preservation of intestinal microflora from mice and rats. PMID- 3328444 TI - [Intermediate cells in the pancreas and cell transformation]. AB - The paper reviews the medical literature concerning the occurrence and several possible explanations of the origin nature of pancreatic intermediate cells present. Electron microscopic studies of the human pancreas and results of animal experiments in the last years strongly suggest that cells in the wall of small pancreatic ducts (ductules) may develop into duct cells, exocrine pancreatic cells (acinar cells), endocrine islet cells, and hepatocytes even in the adult organism. This suggests that transitional cells arise from the known types of pancreatic intermediate cells during this process. The development of the different cells may start from a pool of omnipotent cells (entodermal stem cells of the foregut) present in the walls of the ductules, or from undifferentiated cells, reflecting their embryonic potential as a result of proliferation of duct cells (i.e. indirect cellular transformation = metaplasia of duct cells). PMID- 3328445 TI - Pseudolymphoma (inflammatory pseudotumor) of the liver. AB - Two small pseudolymphomas of the right liver lobe were incidentally detected at autopsy in a 85 year old female patient with a large ulcerating carcinoma of the stomach. Most of the lymphocytes and plasma cells produced IgA and lambda light chains, a few also kappa light chains. These tumors may also be classified as inflammatory pseudotumors of the liver. PMID- 3328446 TI - [History of the Pathologic Museum of the Berlin Charite. 3. On the microcephalic brothers Michael and Friedrich Sohn of Kiwitsblott]. AB - The historical events relating to 2 microencephalic brothers born in Prussia around 1815 and 1822 are presented. After their deaths in 1835 and 1842 respectively they were made accessible to the anatomical museum of the Berlin University. Later the skulls, casts and detailed contemporary descriptions of their development and behaviour as well as original correspondence relating to obtaining the specimens came to the Pathologic Museum of the Charite where they can be found today (recently rediscovered). PMID- 3328447 TI - [Special conditions for the cultivation of genetically engineered microorganisms]. AB - Using recombinant strains recently the cultivation of microorganisms for biotechnological purposes has reached a qualitative new level. With respect to the optimization of such cultivation processes appropriate variations of genetical, physiological and biochemical parameters will be necessary. This review summarizes trends of construction of vectors and problems of correlations between hosts and vectors with regard to their application in discontinuous and continuous bioreactor-procedures. PMID- 3328448 TI - [Transabdominal ultrasound tomography of the lumbar intervertebral disks and the lumbar canal]. AB - The transabdominal sonographic examination of the lumbar intervertebral discs and the lumbar canal was carried out on 50 patients, for whom no existed clinical symptoms for a lumbosacral nerve root lesion. The sonographic device used was a mechanical sector scanner with a transducer with a frequency of 3.5 MHz. The transversal representation of the lumbar intervertebral discs and the lumbar canal was successful mainly at the height of the intervertebral space L4/5 (96%), less frequent at the height L3/4 (74%), L5/S1 (70%) and L2/3 (18%). The intervertebral disc and the intraspinal space at the height of the disc can be assessed in a transversal section, and thus the noninvasive sonographic method represents an improvement of the conventional X-ray-examination of the lumbar spine. PMID- 3328449 TI - [Spinal ultrasound tomography in the diagnosis of lumbar intervertebral disk displacement]. AB - By comparative sonographic and myelographic investigations of 61 patients with lumbar disc herniations and other nerval compressive syndromes, the value of the spinal sonography in the diagnosis of lumbar disc herniation is demonstrated. The transversal transabdominal representation of lumbar disc herniations is successful in 82% of all cases. The sensitivity of sonography amounts to 0.73 in the segment L5/S1 and to 0.92 in the segment L4/5. In connection with the neurological investigation and X-ray films of the lumbar spine, the spinal sonography as a noninvasive procedure can represent an useful alternative to the myelographic diagnosis of the lumbar disc herniation. PMID- 3328450 TI - [Microsurgical ventral surgery in cervical intervertebral disk displacement]. AB - The author deals with his microsurgical method for the removal of cervical intervertebral disk prolapses. Almost the whole intervertebral space is cleared and subsequently stabilised with bones of the patient's iliac crest. PMID- 3328451 TI - [Late results following treatment of peripheral nerve injuries of the upper extremity]. AB - The authors re-examine cases of complete peripheral nerve injury of the upper extremity. Motor activity and sensibility assessment make use of Highet's scale. Some general principles of surgical treatment of peripheral nerve injuries are presented and individual factors which influence its results are worked out, e.g. moment of diagnosis, kind of nerve suture, moment of operation, age of patient, grade of injury, concomitant injuries, and length of graft. Conclusions are drawn for the concept of treatment. PMID- 3328452 TI - [Immunology and the immunodiagnosis of campylobacteriosis]. PMID- 3328453 TI - [Heterogeneity of Shigella flexneri during selective synchronization]. AB - The study of a number of main growth characteristics of S. flexneri (S) cells during the first and second cycles of their cultivation in a solid culture medium in Peshkov's chamber from seed material, nonsynchronized and synchronized by C. E. Helmstetter's method, has revealed that this method does not permit obtaining completely synchronized cultures. Four physiological cell clusters, differing in the time of generation, growth rate, size at the beginning and the end of the cycle and the time of adaptation, have been detected. PMID- 3328454 TI - [Prevention of the formation of the infectious process with biologically active thymic factors in the Salmonella typhimurium challenge of mice coincident with macrophage activation]. AB - A single injection of thymostimulin into mice in a dose of 45 micrograms/kg b.w. enhances the functional activity of macrophages, reaching it maximum on day 10, which prevents the formation of an infectious process in mice challenged with S. typhimurium (LD50). The irradiation of the animals in a sublethal dose leads to the complete abolition of the stimulating effect of thymostimulin on macrophages. The presence of an inducer mechanism of the activation of macrophages by thymostimulin, realized in the production of lymphokines, is suggested. PMID- 3328456 TI - [Epidemiology of candidal infection]. PMID- 3328455 TI - [Modern principles and methods of studying the taxonomy and identification of microorganisms]. PMID- 3328457 TI - [Comparative epidemiological data on cholera during the 7th pandemic in Africa]. PMID- 3328459 TI - [Immunoelectron microscopy study of the progenitors of the granulocytic series in human embryonal and fetal liver]. PMID- 3328458 TI - An import factor in reticulocyte lysates which stimulates processing of several precursors destined for the rat liver mitochondrial inner membrane. PMID- 3328460 TI - [Malignant histiocytosis accompanied by severe hemolytic anemia and hypercalcemia: report of a case and review of the literature]. PMID- 3328461 TI - [A case of celiaco-mesenteric trunk]. PMID- 3328463 TI - Primary T-cell lymphoma of the thyroid. AB - A rare case of non-Hodgkin's malignant T-cell lymphoma of the thyroid in a 79 year-old woman is reported. Light microscopically, the tumor showed diffuse proliferation of lymphoid cells, revealing prominent nuclear irregularity and occasional multilobulated nuclei, and was diagnosed as a diffuse lymphoma of medium-sized cell type. Electron microscopically, the tumor cells were seen to possess irregularly indented nuclei. Immunologic surface marker studies showed that the lymphoma cells were positive for T-lymphocyte-lineage antigens, OKT4 and OKT11, and did not react with B-lymphocyte-associated antigens. These findings indicated that the lymphoma had a T-cell phenotype. PMID- 3328464 TI - [Sensitivities of different stages of erythrocytic Plasmodium falciparum to pyronaridine]. PMID- 3328462 TI - New aspects of clinical and cellular pharmacodynamics of methotrexate with special emphasis on its role in the treatment of acute lymphoblastic leukemia in children. PMID- 3328465 TI - [Determination of the activity of globinase from Plasmodium berghei by radiometry with mouse [3H]globin as a substrate]. PMID- 3328466 TI - [Advantages of ultrasound in the diagnosis of hip development in the neonate]. PMID- 3328467 TI - [Euthyroid endocrine ophthalmopathy]. PMID- 3328468 TI - Effect of water immersion on plasma renin activity, aldosteronaemia and vasopressinaemia in patients with acute non-inflammatory renal failure. PMID- 3328469 TI - Effect of water immersion on plasma renin activity, aldosteronaemia and vasopressinaemia in hypertensive patients before and during the treatment with nifedipine. PMID- 3328473 TI - Pavlovian orienting reflex. AB - The concept of the orienting reflex is discussed from the historical perspective. The following conclusions are proposed: (1) in accordance with the spirit of Pavlov's concept the orienting reflex is a response to a stimulus unexpected in a given situation; (2) the reflex consists of targeting, arousal and perceptual components; (3) the reflex has three stages, which in the targeting component are represented by the movement towards the stimulus, the maintenance of fixation of the stimulus and the return movement; (4) when the reflex is evoked by a new stimulus, perceptual learning occurs in its second stage. The non-orienting targeting reflexes are reviewed. The pretrigeminal cat is discussed as a model for investigation of the ocular orienting reflex. PMID- 3328470 TI - A review of the immunological activities of prostaglandins. PMID- 3328472 TI - Monoaminergic control of affective aggression. AB - The aim of the present study is to present the experimental evidence, mainly that collected over recent years by the author, in support of the involvement of the dopaminergic mesolimbic system in the mechanism of affective aggression in the rat and its interactions with other monoaminergic systems. Dopamine has been found to play an important facilitatory role in affective aggression, accomplished, at least in its essential part by the mesolimbic A10 neurons projecting into the nucleus accumbens septi (NAS). Norepinephrine inhibits this behavior, the effect being mediated by the locus coeruleus ascending neurons reaching NAS and the amygdala (AMY), and involving activation of alpha 1 adrenoceptors. Also serotonergic effects on affective aggression are of inhibitory nature. They are conveyed by the neurons of the dorsal raphe, but not of the median raphe, projecting into the AMY. The NAS does not play any important part in the serotonergic control of aggression. There appears to exist a reciprocal interaction between these three monoaminergic systems in respect to their modulatory function in affective aggression. The significance of these findings for diagnosis, treatment and prevention of violent behavior in the clinic is discussed. PMID- 3328471 TI - Calcium antagonism with felodipine in essential hypertension. Effects on cardiovascular and renal function, the sympathetic and the renin-angiotensin aldosterone systems, glucose tolerance and glucoregulatory hormones. PMID- 3328475 TI - [Xylitol, a cariostatic sugar substitute]. PMID- 3328474 TI - Transplantation to the brain--a new therapeutic principle or useless venture? AB - On the basis of remarkable results from transplantation experiments in animals, the author in 1979 suggested autologous transplantation of catecholamine tissue to the brain as tentative treatment for parkinsonism. Experiences from four patients thus treated are reported comprehensively. Transitory rewarding effects were seen when the transplant was deposited in the putamen. The potential prospects for this principally new therapeutic paradigm are discussed, as well as possible improvements in the method. PMID- 3328476 TI - [Bonding and silver amalgam: basic approach]. PMID- 3328477 TI - [Bonding and silver amalgam. A new clinical approach]. PMID- 3328479 TI - [Prescribed antibiotics in dental therapeutics: innocuousness and toxicity in pregnant women]. PMID- 3328480 TI - [Correlation between bacterial percentages and various clinical indices]. PMID- 3328478 TI - [Variations in the biocompatibility of a dentin adhesive during its clinical use]. PMID- 3328481 TI - The prediction of ovulation and monitoring of the fertile period. AB - Simple and reliable methods have been sought for both predicting and confirming ovulation. Application of these methods could include management of infertile couples to aid in conception and for increasing the reliability of natural family planning (NFP) as a method of birth control. With the advent of specific hormone assays, serial measurements of estrogens, progesterone (and metabolites), and luteinizing hormone have been the gold standard of monitoring ovarian function in women. However, newer and simpler methodologies have been described and are currently either in use or being tested. These include the measurement of basal body temperature (BBT), the evaluation of the volume, consistency and electro conductivity of cervicovaginal fluid, salivary steroid content and cellular enzymatic activity, the use of enzyme-linked immunosorbent assays applied to solid-phase formats, and the investigation of new hormonal molecules as markers of reproductive state and function. These new technologies are described herein and their potential for monitoring ovarian function is discussed. PMID- 3328482 TI - Carcinogen risk assessment. PMID- 3328483 TI - Chocolate. PMID- 3328484 TI - Endogenous proteolytic enzymes in skeletal muscle: their significance in muscle physiology and during postmortem aging events in carcasses. PMID- 3328485 TI - Olive oil: a review. PMID- 3328486 TI - A review of current literature on N-nitroso compounds in foods. PMID- 3328487 TI - The lipid secretion of the meibomian glands. PMID- 3328488 TI - Hypo- and hyperresponders: individual differences in the response of serum cholesterol concentration to changes in diet. AB - The feeding of cholesterol-rich diets to random-bred animals results in marked interindividual differences in the response of serum cholesterol. Certain animals show only small responses (hyporesponders), whereas others develop high degrees of hypercholesterolemia (hyperresponders). Inbred strains of rabbits, rats, and mice differing in their sensitivity to dietary cholesterol are available. In these animals, and also in monkeys, the responsiveness to high-cholesterol diets has a strong genetic basis. The existence of hyper- and hyporesponders also holds in humans, though not as pronounced as in laboratory animals. Repeated trials with the same subjects have shown that persons exist with a consistently low or high response to increased intakes of cholesterol. However, "spontaneous," diet independent within-person variations in the level of serum cholesterol markedly inflate the between-person variation in the response of serum cholesterol; both variations are of the same order of magnitude. Hypo- and hyperresponsiveness to dietary cholesterol extends to other hypercholesterolemic components of the diet. In humans and rabbits hyperresponsiveness to dietary cholesterol is associated with responsiveness to dietary saturated fatty acids. The mechanisms underlying hypo- and hyperresponsiveness to dietary cholesterol have not yet been unraveled. On the basis of available data, we propose that in hyperresponders, compared with hyporesponders, there is a higher hepatic efflux of cholesterol in low-density lipoproteins (LDL), or its precursors, after cholesterol consumption. This may be caused by insufficient inhibition of cholesterol biosynthesis and/or the high capacity of cholesterol absorption in the hyperresponders. The stimulation of LDL production accounts for the increase in LDL cholesterol in serum. The number of hepatic LDL receptors, which may be already decreased in hyperresponders, will decrease further through down-regulation. The receptor-mediated LDL clearance decreases, but the absolute amount of LDL cholesterol taken up by the cells via the receptor and by the receptor-independent pathway increases because of the increased level of LDL cholesterol. In this way a new equilibrium is reached in which LDL production equals LDL catabolism. The phenomenon of hypo- and hyperresponsiveness may have implications for counseling subjects who attempt to lower their serum cholesterol by diet. However, identification of true hyper- and hyporesponders is greatly hampered by within-person fluctuations of the level of serum cholesterol. No simple test is available to discriminate hypo- from hyperresponders.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3328489 TI - The role of dietary cholesterol in the regulation of human body cholesterol metabolism. PMID- 3328491 TI - Aflatoxin and human disease. PMID- 3328490 TI - Sterol carrier and lipid transfer proteins. PMID- 3328492 TI - Reye's syndrome--a continuing enigma. PMID- 3328493 TI - [Chronic lead poisoning with special reference to environmental pollution and childhood. A review]. PMID- 3328494 TI - Aesthetic considerations in the reconstruction of the anophthalmic orbit. AB - Twenty-four patients with severe anophthalmic orbit syndrome were treated with a combination of techniques utilizing autogenous tissue. Autogenous corticocancellous bone grafts were used in the orbit as a volume filler. The temporalis muscle and a fasciae flap with a pericranial flap were used as a curtain to cover the bone grafts and to give a softening effect. The prosthesis used was a regular eye shell. With this method it can be smaller, thinner, and lighter to produce less deformation of the lower lid, particularly when used for a long period of time. In children who have this deformity compounded by small orbits after oncologic treatment, three-wall orbital enlargement is done to achieve a larger orbit, so as to match the normal unaffected socket and produce symmetry. PMID- 3328495 TI - Mechanisms of bone loss: rheumatoid arthritis, periodontal disease and osteoporosis. PMID- 3328496 TI - Influence of rosmarinic acid on opsonization and intracellular killing of Escherichia coli and Staphylococcus aureus by porcine and human polymorphonuclear leucocytes. AB - The influence of rosmarinic acid on the function of porcine and human polymorphonuclear leucocytes was tested. Rosmarinic acid inhibited the chemiluminescence of PMNL, induced by preopsonized Zymosan or phorbol myristate acetate. The killing of Escherichia coli was inhibited by rosmarinic acid at a concentration of 2 mM, but not that of Staphylococcus aureus. The inhibition of the killing was due to an impaired opsonization, caused by an adverse influence of rosmarinic acid on complement activation. Direct effects of rosmarinic acid on the killing mechanisms of PMNL were not observed. PMID- 3328498 TI - [Experimental study of the cellular response on the intraocular lens surface (1). Transmission electron microscopic observation after trypsin treatment]. PMID- 3328497 TI - [Experimental study of the cellular response on the intraocular lens surface]. PMID- 3328500 TI - [Serum beta 2-microglobulin in spinal cord injury patients--its efficacy as a screening test of renal function]. AB - We evaluated the reliability of serum beta 2-microglobulin (beta 2-MG) in comparison with serum creatinine, blood urea nitrogen and creatinine clearance in 164 patients with spinal cord injury. The value of serum beta 2-MG demonstrated the highest correlation coefficient (r = -0.927) in relation to creatinine clearance. The beta 2-MG value reflected the severity of hydronephrosis on excretory urography, with very few false negative values. The value of beta 2-MG is concluded to be one of the best screening tests in evaluating renal function in spinal cord injury patients. PMID- 3328499 TI - [Pheochromocytoma: review of 22 patients and 23 operations]. AB - Twenty-two cases of pheochromocytoma encountered at our department between 1965 and 1986 are reviewed. Eighteen of the patients were adults (26 to 62 years old) and 4 were children (9 to 13 years old). Thirteen were males and 9 were females. In a total of 23 operative procedures, 31 tumors were resected excluding lymph node metastasis. The preoperative accuracy of the diagnostic methods for locating the tumor was as follows. KUB and intravenous pyelography with tomography in 12 of 31 tumors (39%), aortography and/or selective arteriography in 21 of 27 (78%), selective venous sampling for catecholamine level in 4 of 4 (100%), computed tomography in 10 of 10 (100%), ultrasonography in 4 of 6 (67%), and iodine-131 metaiodobenzylguanidine scintigraphy in 4 of 6 (67%) tumors. The tumors resected were cases, as followings, a single unilateral adrenal tumor in 14 (right 6, left 8), bilateral adrenal tumors, bilateral adrenal plus extraadrenal tumors and unilateral adrenal plus extraadrenal in each, one case and extraadrenal tumor in six cases (single 5, multiple 1). Either lumbar or thoracolumbar surgery methods were adapted in 9 of 14 cases with single adrenal and one of 5 with single extraadrenal tumors, and in the remaining 13 cases transperitoneal methods were selected. One patient died on the 6th day after operation from gastrointestinal bleeding. Thus the surgical mortality rate in our series was 4.4%. Of the 3 patients with malignant pheochromocytoma, two (9 and 13 years old) are alive each 192 and 67 months after operation. The former is in a tumor-free condition, however in the latter multiple bone metastasis was detected 37 months after operation. The third patient (29 years old) died 62 months after operation from metastatic hemorrhagic tumors in the liver. PMID- 3328501 TI - [A case of bilateral testicular tumors--a review of 115 cases in Japanese literature]. AB - A case of bilateral testicular tumours of germ cell origin is reported. A 35-year old man with bilateral testicular swelling visited our clinic. Bilateral high orchiectomy was performed. Histological examination of both resected testis revealed typical seminoma. Postoperative irradiation was performed. The patient is doing well after one year of postoperative follow-up without any sign of metastasis. Besides this case, we found 115 cases of bilateral testicular germ cell tumours in the Japanese literature. There were 39 cases with different and 76 cases with similar histology between the left and right testis. The age distribution, location of testis, time of onset and histological classification of these cases is discussed. PMID- 3328502 TI - [Evaluation of a monoclonal antibody-based enzyme immunoassay (IQ(Bio) PAP-AELIA kit) for prostatic acid phosphatase]. AB - The clinical application of enzyme immunoassay (EIA) for prostatic acid phosphatase (PAP) is reported. PAP concentration was measured by an IQ(Bio)PAP AELIA kit. Serum samples were collected from 20 healthy individuals, 31 patients with benign prostatic hypertrophy, 14 patients with prostatis, 23 patients (47 samples) with prostatic cancer and 29 patients with various other malignancies. The coefficients of variation (%CV) in intraassay and interassay ranged from 2.3 to 4.4%, and from 3.0 to 3.6%, respectively. The recovery rate in the dilution test and recovery test were 106.2 +/- 8.9% and 101.3 +/- 6.9% respectively. A significant correlation (r = 0.994, p less than 0.01) was observed between EIA and RIA methods in the prostatic cancer patients. PAP concentration was elevated above 2.0 ng/ml in 0/2 (0%) of the treated patients with stage B prostatic cancer, 1/5 (20%) of those with stage C, 6/16 (38%) of those with stage D, and in 4/5 (80%) of the untreated patients with stage D prostatic cancer. False positive results were seen in 2/31 (6%) of the patients with benign prostatic hypertrophy, 3/14 (21%) with prostatis and 3/29 (10%) of the patients with various other malignancies. In the majority of the false positive cases, elevated levels were only just above the normal value. In conclusion, the PAP level measured by this EIA kit was correlated with the clinical response to hormone therapy for prostatic cancer. PMID- 3328503 TI - [Morphological studies of Escherichia coli in the urine of patients with acute simple cystitis treated with cefbuperazone]. AB - The effects of cefbuperazone (CBPZ) on the morphology of Escherichia coli in the urine of 10 patients with acute simple cystitis were studied by differential interference contrast microscopy and electron microscopy. The urine specimens were collected via catheter before, 5, 10, 15 and 30 minutes after intravenous administration of 0.25 g CBPZ. The minimum inhibitory concentrations for 8 Escherichia coli strains isolated from 8 patients against CBPZ were from 0.05 to 0.2 mcg/ml except one strain. The mean urinary concentrations at 5, 10, 15 and 30 minutes after administration of CBPZ were 274.8, 1181.5, 1343.4 and 931.5 mcg/ml, respectively. Urinalysis improved within 30 minutes after the administration. Filamentous cells of Escherichia coli were observed until 30 minutes after the administration. They had vacuole-like, and spheroplast and bulge formation were also observed in tested cases. CBPZ is suggested to have a high affinity for penicillin-binding protein (PBP) 3 and moderate affinity for PBP 1b and PBP 1a. PMID- 3328504 TI - [Clinical evaluation of combination therapy with Fortimicin and Cefotax in the treatment of complicated urinary tract infections]. AB - Clinical efficacy of combination therapy using Fortimicin (ASTM) and Cefotax (CTX) was studied in 63 patients with complicated urinary tract infections. The patients received 200 mg of ASTM i.m. and 1 g of CTX i.v. twice a day. The overall clinical efficacy of the treatment was evaluated by criteria proposed by the Japanese UTI Committee. The overall clinical efficacy rate was 68.3%. The rate was 67.3% in the patients with single bacterial infection and 72.7% in those with mixed infections. Subjective side effects were observed in one of the patients. Drug related aggravation in laboratory tests was observed in 8 items in 8 patients, but these were mild changes. We concluded that combination therapy with ASTM and CTX was useful for the treatment of complicated urinary tract infections. PMID- 3328505 TI - [Ultrasonic kidney size measurement. 1. In infants and children]. AB - Ultrasonography in a sector scanner at real time was performed on the normal kidneys of 126 males and 101 females up to 12 years of age including infants. The growth of the kidneys was well correlated with the age, height and body weight, but the following findings of the kidney length were obtained when the male and female kidneys were measured in a comprehensive manner. 1) y (mm) = 2.987 X age + 55.029 with 0.864 correlation coefficient and less than 1% risk rate showed a positive correlation with the age. 2) y (mm) = 0.407 X height + 28.045 with 0.879 correlation coefficient and less than 1% risk rate showed a positive correlation with the height. 3) y (mm) = 0.949 X body weight + 50.904 with 0.878 correlation coefficient and less than 1% risk rate showed a positive correlation with the body weight. No difference was recognized between both sexes and the right and left kidneys of infants and school students in their kidney length and thickness. PMID- 3328506 TI - [Ultrasonic kidney size measurement. 2. In normal adolescents]. AB - Ultrasonography of both kidneys was performed, on 231 male and 220 females normal junior and senior high school age adolescents. 12 and 20 years. Kidneys grew in correlation with the age, height and body weight. 1) Relationship between the kidney length and the age was y (mm) = 1.747x + 67,663 with 0.489 correlation coefficient and less than 1% risk rate in males, and y (mm) = 1.550x + 76,719 with 0.374 correlation coefficient and less than 1% risk rate in females. 2) Relationship between the kidney length and the height was y (mm) V 0.305x + 43.852 with 0.360 correlation coefficient and less than 1% risk rate in males, and y (mm) = 0.589x + 9.042 with 0.367 correlation coefficient and less than 1% risk rate in females. 3) Relationship between the kidney length and the body weight was y (mm) = 0.290x + 78.258 with 0.373 correlation coefficient and less than 1% risk rate in males, and y (mm) = 0.490x + 76,286 with 0.450 correlation coefficient and less than 1% risk rate in females. No difference the right and left kidney length was recognized in either sex. The growth of female kidneys was faster than that of male kidneys between the ages of 14-17. No difference was observed in length of the right or left kidney or sex with the age group of 18 or over. PMID- 3328508 TI - [Statistical survey of metastasis of bladder tumors--from the annual of pathological autopsy cases in Japan]. AB - We analyzed 1,821 cases of bladder tumors collected from the Annual of the Pathological Autopsy Cases in Japan, 1978-1982, published by the Japanese Pathological Society to determine the frequency of metastasis and metastatic sites. Study of age distribution revealed that the highest incidence was found in the 70-79 age group and that the male to female ratio was 2.95:1. Histologically, the tumors were transitional cell carcinoma in 1,393 cases (80.5%), squamous cell carcinoma in 185 cases (10.7%), adenocarcinoma in 64 cases (3.7%) and anaplastic cell carcinoma in 62 cases (3.6%). Metastasis was found in 1,275 cases (70.0%). The frequency of metastasis according to histological type was transitional cell carcinoma in 960 (69.8%), squamous cell carcinoma in 127 cases (76.5%), adenocarcinoma in 51 cases (86.4%) and anaplastic cell carcinoma in 53 cases (89.8%). Metastasis occurred in order of decreasing frequency in lymph nodes, lungs, liver, bones, peritoneum, kidneys, intestines, prostate, ureters and uterus. These findings were compatible with several previous statistical surveys of autopsy cases of bladder tumor. PMID- 3328507 TI - [Complication during the period of anuria after cadaveric transplantation--with special reference to wound bleeding]. AB - Some period of anuria is usually expected after cadaveric renal transplantation, and hemodialysis is necessary during the period. Postoperative bleeding in the anuric period is not uncommon and usually can be easily controlled with adequate conservative treatment. However, it becomes uncontrollable in some cases and causes a series of serious complications. Out of 22 patients having undergone cadaveric renal transplantation in our hospital, six patients had postoperative bleeding. On investigation of these cases, we found that not only a hemorrhagic tendency due to uremia but also hemodialysis is a risk factor of bleeding in the wound. PMID- 3328509 TI - [Two cases of synchronous bilateral renal tumors]. AB - Case 1: A 56-year-old man visited us complaining of gross hematuria. Because of his refusal to undergo a surgical operation, we performed embolization and chemotherapy, which were ineffective and he died of cancerous cachexia. Case 2: A 59-year-old female with microscopic hematuria was referred to our clinic. Left partial nephrectomy and right radical nephrectomy were done in a two-stage operation at a 3 month interval. She is now well without sign of recurrence at 9 months after the last operation. PMID- 3328510 TI - [A case of primary psoas abscess with paravesical extension]. AB - We report a case of primary psoas abscess with paravesical extension. A 16-year old man who had suffered from remittent fever for two months was admitted to our clinic. He had no urological symptoms or walking disturbances, but ultrasonography showed a well-defined echoic mass at the right paravesical space. Computed tomography confirmed this finding, and right psoas muscle appeared to be enlarged with irregular low density areas. Percutaneous drainage for right paravesical abscess was performed, and 15 ml of pus was obtained. The bacterial and fungal culture of the specimen resulted in no growth of any organisms. Six days after percutaneous drainage, he received en bloc resection of right paravesical abscess with segmental resection of bladder wall and peritoneum adherent to it. Furthermore, the affected region of the right psoas muscle was salvaged as highly upward as possible. Surgical specimen disclosed, pathologically, a non-specific granuloma with stellate necrosis. This finding suggested a feature of cat-scratch disease, tularemia, lymphogranuloma venereum and Yersinia infection. We reviewed the related literature on diagnostic images such as CT, ultrasonography and 67Ga scintigraphy. Moreover, bacterial causes and therapy of primary psoas abscess are discussed. PMID- 3328511 TI - [A case report of leiomyoma of the urinary bladder]. AB - A 69-year-old male patient developed gross hematuria. Cystoscopy revealed a very small mass growing from the dome. The patient underwent transurethral resection of the mass under epidural anesthesia. Pathological examination of the resected specimen revealed submucosal leiomyoma of the bladder. The pathology, clinical manifestations, radiological and cystoscopic findings, treatment and prognosis of vesical leiomyoma are reviewed. PMID- 3328512 TI - [Rhabdomyosarcoma of the prostate: report of a case and review of the literature]. AB - Rhabdomyosarcoma of the prostate is a rare tumor and its prognosis is extremely poor. However, the survival rate has been gradually improved by using combined chemotherapy. A 17-year-old man with the chief complaint of dysuria was referred to our hospital on April 7, 1986. Prostatic needle biopsy was performed and pathological diagnosis was rhabdomyosarcoma of the prostate. The patient was given preoperative combined chemotherapy consisting of actinomycin D and cyclophosphamide. Total cystoprostaurethrectomy and ileal conduit were performed on April 30, 1986. He underwent postoperative combined chemotherapy (vincristine, actinomycin D, cyclophosphamide). He is well 13 months after his initial symptoms and is clinically free of tumor 12 months postoperatively. Forty-two cases of rhabdomyosarcoma of the prostate including our case were collected from the Japanese literature and reviewed with respect to the multimodal treatment and prognosis. PMID- 3328513 TI - The evaluation of immediate hypersensitivity reactions: current concepts and future directions. AB - In the past, and for the majority of clinicians, methods of evaluating allergic reactions have centered on attempts to associate specific allergen contact with induction of symptoms. In this regard, it has always been emphasized that a careful history obtained by a knowledgeable physician is the single most important aspect of an allergic evaluation. Attention to the nature of the reaction and its proximity to possible allergic contact, and variations based on seasonal, regional and climatic changes, as well as avoidance and modification by medication can do more to establish a probable cause and effect relationship than any isolated test. However, there are now a multitude of in vivo and in vitro tests which may be employed to confirm or deny a clinical suspicion of a specific allergen-induced reaction. The majority of these procedures have less variability but suffer from the traditional problems of the imprecision of allergens. Additionally, in the case of skin testing, inhalation challenges and histamine release, these tests may be used to quantitate the degree of reactivity by titration of the response with varying doses of antigen. The improvement in allergy testing has occurred because of the better quantitation of some in vitro testing and will improve with standardization of extracts. The latter may some day include the use of recombinant allergens. PMID- 3328514 TI - Retrospective study of ketotifen protective action in different allergopathies. AB - There is no doubt that ketotifen has continued to be an effective prophylactic anti-allergic drug throughout the years since its discovery. Therefore, we decided to perform a retrospective study of this pharmacologic agent to evaluate its efficacy, duration of treatment, as well as its tolerance in different allergic processes. A total of 1,000 histories of allergic patients were reviewed and 450 were selected by chance from 1981 through 1984. The patients were divided as to their diagnostic etiology, whether affected by pollen or house dust. Ketotifen efficacy was graded from 0-3 (bad, regular, good and excellent), according to its clinical evaluation. In general, children responded better to ketotifen treatment than adults (reduction in other symptomatic drug intake), although statistical significance was found in both populations. However, drug efficacy was better in pollen than house dust. Induced asthma and rhinitis in the children population. On the other hand, no statistical difference was found between sensitization to house dust or pollens in the adult population. To be truly effective, ketotifen should be taken for at least 3 months or more. We only found 12 (2.66%) patients who presented somnolence: the rest tolerated the drug well, with no secondary side effects. PMID- 3328516 TI - [Status of the hemostasis system in physiologic pregnancy, labor and the puerperium]. PMID- 3328515 TI - Eosinophilic gastroenteritis: a description of a new case with serous affectation. AB - We discuss a case of a 51 year old female who presented periodic episodes of abdominal pain, nausea and vomitus consisting of food elements and in addition in the last crisis presented ascites and increased abdominal circumference. The laboratory studies performed included the remarkable increase in eosinophils found in peripheral blood and ascitic fluid with the rest of the laboratory findings within the normal limits (biochemical, proteinogram, Igs, urine and stool examination, and negative food provocation test). Radiography demonstrated swelling of the gastric wall at antral level and the small intestinal wall. A gastric sample was taken via endoscopy which established the diagnosis of EG. EG is a disease of still disputable etiopathogenesis. Some think it is mediated by type I hypersensitivity mechanism and others (like our case) mediated by immunologic mechanism different from atopy which on occasions form part of a systemic feature. Regarding the role of eosinophil, it seems to be important as latest studies have found a relation between the degree of cell degranulation and the degree of histologic lesion. From the distinct form of EG (muscular, mucosa, serosa), EG with involvement of the serosa layer is the less frequent. It is usually associated to some other layer (generally muscular) and presenting ascites. Some authors denominate mixed-type EG to these forms whereby important involvement of more than one layer of the digestive tract is demonstrated. PMID- 3328518 TI - [Ultrasonic and telethermographic diagnosis of serous mastitis]. PMID- 3328517 TI - [Various indicators of endocrine function of the feto-placental complex in women with diabetes mellitus. Diabetic fetal macro- and microsomia]. PMID- 3328520 TI - Amatus Lusitanus on tumors of the skin. PMID- 3328519 TI - Peroxisomal disorders. AB - The different types of adrenoleukodystrophy are considered with their clinical and biochemical features, particularly the excess of very-long-chain fatty acids. Then other conditions which show this latter finding are described, including the Zellweger cerebrohepatorenal syndrome, hyperpipecolic acidemia and Refsum disease. The role of peroxisomes is discussed and the different ways in which their functions can be disordered. The possibilities of treating these diseases is at the moment limited but examples are given of research already carried out in this field. PMID- 3328522 TI - [New technics applied to embryology (horseradish peroxidase and monoclonal antibodies)]. PMID- 3328521 TI - Chaucer and medicine. PMID- 3328525 TI - [Hemochromatosis]. PMID- 3328524 TI - [Surgery of obesity]. PMID- 3328523 TI - [Articular chondroprotection]. PMID- 3328526 TI - [Porphyria hepatocutaneous tarda. Etiopathogenesis and physiopathologic treatment]. PMID- 3328527 TI - [Clinical aspects of porphyria hepatocutaneous tarda]. PMID- 3328528 TI - [Effect of spontaneous positive pressure breathing on the lung function in patients with diffuse peritonitis]. PMID- 3328529 TI - [Sphaerospora renicola (Myxosporidia), the agent of protozoal swim bladder inflammation in young carp (renicola sphaerosporosis)]. PMID- 3328530 TI - [A historical survey of the nomenclature of the lanceolate liver fluke Dicrocoelium dendriticum]. AB - The correctness of the name Discrocoelium dendriticum given to the lanceolate liver luke is discussed in the form of a literature review. Possible reasons are discussed for the peculiar first finding of this parasite in the gut of a swordfish. D. dendriticum is regarded as the valid name of this fluke. PMID- 3328532 TI - Endocytic activities of Sertoli cells in the rat. PMID- 3328533 TI - Role of basement membranes in cell differentiation. AB - Extracellular matrices have diverse biological effects, including promoting the growth and differentiation of various cells of epithelial origin. The components of one of these matrices, the basement membrane, are discussed, as well as studies using these components alone or in combination with cells in culture. The particular response observed varies with the cell type examined and appears to be dependent on multiple interactions with components of the matrix. Potential uses for a basement membrane-derived matrix in vitro and in vivo are being developed. PMID- 3328531 TI - Biochemistry of Haemonchus--a review. AB - Haemonchus biochemistry has been reviewed under the subheadings chemical composition (carbohydrates, lipids, proteins, amino acids, nucleic acids, hormones, inorganic elements, pigments), absorption/transport, biosynthesis (carbohydrates, lipids, proteins, amino acids, nucleic acids), catabolism/utilization (carbohydrates-glycolysis, TCA cycle, CO2 fixation, electron transport system, pentose pathways, glyoxylate cycle, strain variations in energy metabolism; lipids, proteins), biochemistry in taxonomy and miscellaneous. PMID- 3328534 TI - Cell-cell interactions in the testis. AB - In conclusion, the information available indicates that the interactions between different cell types in the testis play an important role in the control and maintenance of testicular functions. Further characterization of these interactions will clearly provide insight into the cell biology of the testis and into the regulation of cellular differentiation, function, and growth. It is apparent that no testicular cell type is autonomous, but that there is communication and cooperation between all cell types in the testis. PMID- 3328535 TI - Gonadal development and gametogenesis in the hypogonadal mouse are restored by gene transfer. AB - These results describe controlled regulation of a mammalian neural gene in transgenic mice. Analysis of truncated GnRH-GAP genes in transgenic mice will enable us to define the DNA sequences responsible for this control. Furthermore, by separate mutation of the GnRH and GAP coding sequences we will be able to determine the relative importance of these two peptides in the development and maintenance of reproductive function. PMID- 3328536 TI - The role of the epididymal epithelium in the development of mammalian sperm fertilizing capacity in vivo and in vitro. PMID- 3328537 TI - Preliminary observations on a second Mr approximately equal to 24,000 membrane molecule from rat spermatozoa. AB - Preliminary data are presented to show that the integral membrane glycoprotein found on rat cauda epididymal spermatozoa is one of two Mr = approximately 24,000 molecules that are associated with sperm membranes. The second molecule can be differentiated from the glycoprotein by a variety of antibodies and can be shown to be present in spermatozoa and in residual bodies present in the epididymal fluid. The second molecule can be localized immunocytochemically in spermatids and Leydig cells in the testis. PMID- 3328538 TI - Further characterization of a model system for the study of human epididymal physiology and its relation to sperm maturation. AB - Some preliminary speculations about the possible participation of epididymal antigens in sperm function may be supported by the above data. On the one hand, the reduction in the amount of antigens and their abnormal localization on spermatozoa from infertile patients may be coincident with our view about participation of epididymal antigens in the development of zona pellucida binding ability and fertilizing capacity by spermatozoa during maturation. This hypothesis is derived from experiments showing that immature hamster spermatozoa gain their ability to recognize and bind to zona pellucida and to penetrate homologous oocytes when exposed to preparations enriched in androgen-dependent epididymal secretory proteins or preincubated in conditions that favor their interaction with these proteins. Supporting our viewpoint for such a role in humans is evidence showing the progressive development of the ability to interact with hamster denuded oocytes as human spermatozoa pass along the epididymis. On the other hand, the apparent correlation between the loss of epididymal antigens during capacitation and the increased fertilization of human oocytes in vitro may be reminiscent of the removal of a decapacitation or acrosome stabilizing factor known to occur in many species and that must be removed prior to fertilization. Pending further understanding of their physiological role, the androgen-dependent epididymal proteins may become a useful marker of epididymal function and/or of sperm capacitation in humans. Within this context, we wish to stress the potential value of the model system that we have developed for the study of human epididymal physiology. PMID- 3328540 TI - Sex-reversed mice and sex determination. PMID- 3328539 TI - Cytoskeletal assemblies of mammalian spermatozoa. AB - It is becoming increasingly evident that the different domains of the mammalian spermatozoa possess distinct cytoskeletal assemblies. In this paper we have discussed three assemblies, found in the acrosomal, postacrosomal, and midpiece segment, respectively. Each has a distinct substructure and associates with specific sperm-membrane systems. Their protein compositions are currently unidentified, and they may be comprised of sperm-specific polypeptides. Analysis of their formation and fate during sperm-egg interaction should provide valuable insight into their role in the development of cell polarity and in the membrane mediated steps of fertilization. PMID- 3328541 TI - Acquisition of hormone-mediated mechanisms regulating testicular steroidogenesis during development. AB - Our studies have demonstrated that in the fetal rat Leydig cell, estradiol causes an up-regulation of its receptor and an induction of the regulatory mechanism (late steroidogenic lesion) that is similar to that observed in the adult rat Leydig cell. The absence of this regulation in fetal life is due to a very low level of aromatization capacity, with lack of up-regulation and/or induction of estrogen receptor by estradiol. Higher doses or frequent administration of LH is able to elevate aromatase activity and consequent E2-receptor-mediated action for the induction of gonadotropin-mediated desensitization in fetal cells. Our studies have revealed a small population of adult-like Leydig cells in the fetal testis and the emergence of a functional adult-like population from the fetal Leydig cell induced by gonadotropin treatment. The in vitro fetal Leydig cell culture system has permitted the analysis of cellular actions of gonadotropin with particular reference to the role of tropic hormone and estrogen in the development of late steroidogenic lesions during Leydig cell maturation. Future research with this system will help to clarify further the modulatory mechanisms responsible for emergence of the adult cell population. PMID- 3328542 TI - The occurrence and distribution of lamin proteins during mammalian spermatogenesis and early embryonic development. AB - Based on current evidence it is apparent that the lamins undergo a dynamic reorganization during both spermatogenesis and early embryonic development, processes that presumably underscore unusual requirements in germ-cell differentiation and embryonic development. PMID- 3328544 TI - [Maxillofacial abnormalities of syndromes of the 1st branchial arch]. AB - Hemifacial microsomia and Treacher Collins syndrome are the most frequent among the first and second branchial arch syndromes to include anomalies of the facial skeleton. Hemifacial microsomia is almost always unilateral and is characterised by hypoplasia or agenesis of the mandibular ramus. Treacher Collins syndrome is always bilateral and involves specifically the zygomatic bones. The treatment of skeletal anomalies is seldom started before 10-12 years of age, except in severe form with major aesthetic impairment. Such cases are treated at the beginning of school age, on and after 6-8 years. Several operations, including osteotomies of the jaws and bone grafts, are usually necessary to achieve an acceptable result. PMID- 3328545 TI - [Paris Dermatology Seminar, 11-14 March 1987. Papers. Issue dedicated to the memory of Prof. Robert Degos]. PMID- 3328547 TI - [Necrosis of the scalp and cranial vault in Horton's disease]. PMID- 3328543 TI - [Solid cold thyroid nodule. Current data]. AB - Attitudes adopted when confronted with a solid cold thyroid nodule are analyzed in the light of recent developments in paraclinical data represented essentially by results of immunological, ultrasound and fine needle cytopuncture examinations. The use of these new surveillance technics frequently allows surgery to be deferred, while if on the contrary operation is decided then it usually now involves both thyroid lobes to avoid nodular recurrence and repeat surgery. Postoperative follow up surveillance is essential to ensure individual adaptation of attitude: therapeutic abstention, suppressive or possibly compensatory treatment. PMID- 3328548 TI - [Disorders of tryptophan metabolism in dermatology]. PMID- 3328549 TI - [Psychogenic buccal paresthesias (stomatodynia and glossodynia)]. PMID- 3328546 TI - [Cutis marmorata telangiectatica congenita. 4 new cases and review of the literature]. AB - Cutis marmorata telangiectatica congenita (CMTC) is characterized by a persistent vascular mottling of the skin, usually on the limbs. Four cases (2 males and 2 females) followed up for varying lengths of time are reported. In the first patient, whose vascular lesions were mild, careful re-examination after 10 years revealed some scars. In the second patient the lesions were located on the right side of the body, notably on the leg; 6 years later atrophic scars and a brownish plaque were visible on that leg. In the third patient the lesions occupied almost the entire body, although one side was more affected than the other and hypotrophic; the child's face was asymmetrical because of hypoplasia of the jaw and curvature of the nose; after 1 year the patient's general condition was satisfactory and the skin lesions were less evident but still present. In the fourth patient hypoplasia of a lumbar vertebra was discovered; the skin lesions were similar to those observed in the third patient. Examination of the deep vessels, performed whenever possible, did not show any abnormality, but the possibility of future vascular defects, such as varicosities, must be considered. While some authors emphasize the functional character of the disease, in our opinion the high frequency of multiple associated congenital abnormalities makes CMTC not only a vascular disorder but also a syndrome including other neuroectodermal and mesodermal defects. Therefore, any patient presenting with the cutaneous changes typical of CMTC should be examined with this in mind. PMID- 3328550 TI - [Ingrown nails]. PMID- 3328551 TI - [Linear IgA disease in adults. Review of the literature]. PMID- 3328552 TI - Aetiology of diarrhoea in Singapore. AB - Stools from acute diarrhoea were investigated for bacterial and viral pathogens. In one study involving 63 young children in a paediatric ward, 70% of the stools were positive for the pathogens looked for of which 37% contained bacteria, 22% viruses and 11% mixed cultures of bacteria and viruses. In another study in which 130 watery stools from routine specimens of patients of all ages were investigated, 36% were positive for pathogens with 11% bacteria, 18% viruses and 7% mixed pathogens. The high incidence of bacterial diarrhoea in young children was attributed to gastroenteritis caused by Salmonella species. Salmonella and rotavirus were found the most common pathogens in bacterial and viral diarrhoeas, and the most susceptible age group was under 5 years-old. PMID- 3328553 TI - Sero-survey for Legionella pneumophila antibodies--Singapore experience. AB - One hundred and fifty blood bank donors were sero-surveyed for legionella antibodies by indirect immunofluorescence test using a polyvalent antigen group (1 to 4). 20% of the group surveyed had an antibody titre greater than or equal to 16 to the organism. This paper also reports a study on 166 hospitalised acute pneumonia patients. The sera from these patients were screened for L. pneumophila antibodies; 5 of the patients had significant antibody titre greater than or equal to 256 which is diagnostic of legionellosis. PMID- 3328554 TI - Leprosy in Singapore. AB - The incidence of leprosy in Singapore is declining over the past 20 years. More than one third of new cases are now over 50 years while no child under 5 years has been affected since 1970. Male to female ratio is 2:1. Indians are more significantly affected compared to the other races and a higher proportion has tuberculoid leprosy. Tuberculoid leprosy accounts for 50.4% of cases seen during the past decade. Case detections from household contacts is still worthwhile as it accounts for 3% to 13.5% of the yearly incidence of the disease. The first four cases of dapsone resistance was confirmed in 1969. Since then the yearly incidence of clinically diagnosed dapsone resistant cases averaged 2.9 per thousand. Hence, various regimens of multiple drug therapy have been instituted. PMID- 3328555 TI - Newer methods for the detection of Chlamydia trachomatis in genital specimen. AB - Conventional culture isolation methods for detecting Chlamydia trachomatis infections are laborious, expensive, technically demanding and not widely available. Recently, non-culture methods which detect chlamydial antigens have been introduced. These methods utilise immunofluorescence (IF), enzyme immunoassay (EIA) or DNA hybridisation techniques. DNA hybridisation techniques are presently, still experimental. IF and EIA tests are widely available and are suitable alternatives to culture isolation for laboratories who wish to provide a chlamydia-service. The sensitivities and specificities, and advantages and disadvantages of these systems are discussed. PMID- 3328556 TI - Chancroid--a review. AB - Chancroid is a sexually transmitted disease caused by Haemophilus ducreyi. The infection is reported to be more common in the tropics. Isolation of H. ducreyi is difficult even in the best of hands. The diagnosis of chancroid is often clinical. Most chancroidal ulcers are polymicrobial in nature and this has resulted in conflicting reports of the efficacy of antibiotics used in the treatment of chancroid. In-vitro testing of clinical isolates indicated a wide variation in the prevalence of resistance to various antibiotics in different geographic areas. This paper reviews the epidemiology, diagnosis and management of chancroid. PMID- 3328557 TI - Parasitic infections in Singapore. AB - This paper describes various parasitic infections which are encountered in Singapore. These include the soil transmitted helminths, pinworms, Clonorchis/Opisthorchis, Hymenolepis, filariae, malarial parasites, Toxoplasma and other protozoal infections. The reasons for the transmission of these parasites in the republic are discussed. Some of the problems associated with their diagnosis are highlighted. PMID- 3328558 TI - Water resource development and prevention of malaria. AB - The construction of dams across the mouths of major tidal rivers in the development of the Kranji Reservoir, Western Catchments Scheme and the Sungei Seletar Reservoir in Singapore created suitable environmental conditions for the propagation of anopheline brackish-water breeders. The employment of foreign contract workers from malarious areas for the projects further increased the potential risk of malaria transmission. However, constant vigilance and environmental management aimed at the permanent elimination of vector breeding habitats, supplemented with chemical control and anti-parasite measures successfully prevented the reintroduction of malaria in these highly receptive and vulnerable areas. PMID- 3328560 TI - [Value of angioscanography in the morphologic exploration of hypophyseal adenomas]. AB - Considerable progress has been made in the morphologic study of pituitary due to the availability of angioscan programs. An exceptional case is presented of a persistent intrasellar trigeminal artery associated with prolactinoma. Based on technological progress in CT scan imaging the place of angiographic explorations in the investigation of pituitary adenoma is reconsidered. PMID- 3328561 TI - Experimental animal models of eating disorders. Recent pharmacological studies. AB - Until recently, the amount of standardized laboratory food eaten--during a short period of time--by starved young and lean animals was the only parameter used to determine the effects of drugs on feeding behaviours. Now with the introduction of recent physio-pathological concepts and new behavioural designs the information obtained from pharmacological studies is much more elaborate. It concerns not only the ingestive behaviours but also the peri-prandial behaviours. It gives specific indications on how the effects of different drugs may be affected by changes in the "milieu interieur" and by the characteristics of environmental factors. Different experimental models are described; results obtained with these models are discussed. PMID- 3328559 TI - [Inhibin]. AB - Chemical structure of inhibins is known: there are molecules constituted by two subunits alpha and beta (A or B). Inhibin displays actions at hypophyseal, hypothalamic and gonadal levels. Produced by granulosa cells in female and by Sertoli cells in male, inhibin synthesis is stimulated by FSH, androgens and reduced by hypophysectomy and progesterone. At the present time, there is no evidence for a signal from germinal cells to modify inhibin production. Inhibin secretion parallels with follicular maturation as aromatase activity whereas luteinization arrests its production. Sperm inhibin levels are correlated with spermatozoa number. Its administration to the sheep induces either an anovulation or an increase of ovulation rate according to the scheme of treatment. PMID- 3328563 TI - S-100 protein and neuron specific enolase (NSE) immunoreactivity in pleomorphic adenomas of the salivary glands and its relationship to the composition of their extracellular matrix. PMID- 3328562 TI - Ultrastructural-immunocytochemical localization of endogenous calcitonin in osteoblasts of silicon-treated rats. AB - Immunoreactivity to endogenous calcitonin was studied in osteoblasts from calvaria of neonatal rats, by immunocytochemistry with the use of ultrathin sections obtained by cryoultramicrotomy. The influence of a silicon-treatment on the localization of endogenous calcitonin in osteoblasts of rats, was tested. Endogenous calcitonin-like immunoreactivity was observed in osteoblasts of calvaria of control and of silicon-treated rats, and showed a similar subcellular localization in both types of rats. Calcitonin was observed at the plasma membrane level, in the cytoplasmic matrix, and in the nucleus. The results provide immunocytological evidence for: 1) the internalization of calcitonin in osteoblasts of rat calvaria; 2) a similar localization of calcitonin in osteoblasts of control or silicon-treated rats. PMID- 3328564 TI - [Immunohistochemical demonstration of intermediate filaments. Value in routine histopathological diagnosis]. PMID- 3328565 TI - In vitro chemosensitivity of Plasmodium falciparum to four chloroquine derivatives. AB - The antimalarial activity of four chloroquine derivatives has been assessed in vitro by the Trager and Jensen technique against the strain of Plasmodium falciparum FCC, 2spp. Monodesethyl-chloroquine possessed a significant activity, reducing the parasitaemia to 5% with 2 nM ml-1 (base). The hydroxy-metabolite showed a slight activity, reducing the parasitaemia to 39.5% with 2 nM ml-1 (base). No activity was found with the amino-metabolite and the pyrrolidinyl chemical derivative. The anti-malarial activity of monodesethyl-chloroquine should be considered for pharmacokinetics and for optimizing chloroquine treatments. PMID- 3328566 TI - Echinococcus multilocularis: variation among samples of cyst fluid in binding of parasite-specific antibodies. AB - Some of the factors influencing the sensitivity of ELISA in serodiagnosis of infections with Echinococcus multilocularis were examined. The results obtained suggest that, in contrast to E. granulosus, the variability in the antibody binding capacity of various samples of cyst fluid of E. multilocularis cannot be explained by differences among parasite strains, species of host, cyst locations within the host, cyst fertility or protein concentration of the sample. PMID- 3328567 TI - Ancylostoma ceylanicum: migratory behaviour in golden hamsters after oral and parenteral infection. AB - The infectivity and migratory pattern of Ancylostoma ceylanicum infective larvae (L3) were investigated in hamsters infected by various routes. Following oral administration 40-70% of L3 attained maturity and there was no tissue migration. Following subcutaneous inoculation a small number (1-1.2%) of L3 attained maturity in the intestine after completing the broncho-oesophageal journey. Larvae which penetrated the skin also became adult in the intestine. Most of the larvae entering parenterally remained at the site of infection and in the tracheal region for more than 100 days without undergoing any development, other than desheathment. Those transmitted orally to naive hamsters developed in the normal way. Larvae inoculated parenterally into female hamsters were able to infect offspring in milk, but could not cross the placental barrier. PMID- 3328568 TI - A mark-recapture experiment with the filariasis vector Anopheles punctulatus in Papua New Guinea. AB - A capture-recapture experiment with the filariasis vector Anopheles punctulatus from Papua New Guinea (PNG) is described. Eight hundred and ninety-seven engorged females collected indoor resting or in landing catches were released, and 82 were subsequently recaptured. Infection rates were higher in recaptured mosquitoes than in unmarked ones. Recapture rates declined exponentially with distance from the release site, but an infected female was recaptured 1.8 km from the release site. The estimated oviposition interval of 2.90 days was shorter than that obtained from the same species elsewhere in PNG, but daily survival rates were similar. Infection with Wuchereria bancrofti did not appear to affect the survival of the mosquito. Collections adequately sampled the resting population from inside a room of an experimental house. PMID- 3328569 TI - Antimalarial activity of bisdesethylchloroquine against P. falciparum and P. berghei berghei. PMID- 3328570 TI - XAC, a functionalized congener of 1,3-dialkylxanthine, antagonizes A1 adenosine receptor-mediated inhibition of renin secretion in vitro. AB - Previous studies have shown that activation of A1 and A2 adenosine receptors leads to inhibition and stimulation respectively of renin secretion by rat renal cortical slices. In the present studies, rat renal cortical slices were incubated in the presence of adenosine deaminase, to destroy any adenosine released from the preparation. N6-cyclohexyladenosine (CHA) had a biphasic effect on renin secretion: submicromolar concentrations inhibited concentration-dependently, and there was an inflection in the dose-response curve near 1 microM CHA such that higher concentrations produced a concentration-dependent relative stimulation, which became an absolute stimulation (i.e., secretory rate was higher than control) at 50 microM. These findings are consistent with A1 and A2 adenosine receptor-mediated inhibition and stimulation of renin secretion, respectively. Xanthine amine congener ["XAC," 8-(4-((2-aminoethyl) aminocarbonylmethyloxy)phenyl-1,3-dipropyl xant hine] has been shown by others to be a very potent adenosine receptor antagonist with selectivity for A1 receptors. It antagonized both CHA-induced inhibition (Ki approximately 2 x 10(-9) M) and CHA-induced stimulation (Ki approximately 5 x 10(-8) M) of renin secretion. Thus, XAC exhibited a 25-fold selectivity for CHA-induced inhibition of renin secretion in comparison with CHA-induced stimulation. In comparison with previous results, XAC is approximately 3 orders of magnitude more potent than theophylline. In conclusion, occupation of adenosine receptors can lead either to inhibition (A1 receptor-mediated) or stimulation (A2 receptor-mediated) of renin secretion, and XAC is a very potent and selective antagonist of CHA-induced changes in renin secretion. PMID- 3328571 TI - [Studies on ultrasonic diagnosis of pancreatic cancer]. PMID- 3328572 TI - [Cerebral abscess caused by Proteus mirabilis in the neonatal period]. AB - Eight cases of cerebral abscesses due to Proteus mirabilis in the newborn period are reported. The authors emphasize the insidiousness of the clinical features, and the use of ultrasound screening for an early recognition, essential for the therapeutic results. PMID- 3328573 TI - [Group B streptococcal inguinal adenitis and cellulitis in newborn infant]. PMID- 3328574 TI - [Treatment of diabetes in children under 3 years of age. Indications, methods and results]. AB - Before modern methods of diabetes management were available, the achievement of strict glycemic control was considered almost impossible in most children with early onset of the disease. The present results obtained over 2 years in 31 children aged 21 +/- 2 (SEM) months at the onset of the disease indicate the efficiency of intensive conventional therapy in 21 of them: glycosylated hemoglobin averaged 7.0 +/- 0.3% (N = 4.7 +/- 0.7%) during the observed 26 +/- 7 months, with only 0.02 +/- 0.01 hypoglycemic attack per patient-month and no diabetic ketoacidosis. In the remaining 10 children, who resisted intensive conventional therapy, we used insulin pumps to improve blood glucose control, with the following results over 21 +/- 4 months: Glycosylated hemoglobin decreased from 9.3 +/- 0.3% (before pump) to 8.0 +/- 0.4% (p less than 0.05). The frequency of hypoglycemia decreased dramatically from 1.7 +/- 0.7 to 0.03 +/- 0.01 episode per patient-month. The frequency of ketonuria and ketoacidosis was unchanged. We concluded that intensification of therapy through conventional means, or pump treatment if necessary, allows a long term efficient control of blood glucose in preschool children. PMID- 3328576 TI - [Nemaline myopathy: a syndrome with severe neonatal manifestation]. PMID- 3328575 TI - [Congenital nephrotic syndrome associated with congenital toxoplasmosis]. AB - The authors report the case of a 1 month-old infant presenting with congenital toxoplasmosis associated with nephrotic syndrome and microscopic hematuria. Percutaneous renal biopsy showed a diffuse mild increase in mesangial cells and matrix, but immunofluorescence was negative. Electron microscopy revealed the presence of extensive fusion of foot processes. A review of the nephropathy of congenital toxoplasmosis is presented. Outcome seems to be favorable under steroid therapy. The pathophysiology of nephropathy is discussed, as well as the relationships or coincidence between congenital toxoplasmosis and nephrotic syndrome. PMID- 3328577 TI - [Anti-measles vaccination and malaria]. PMID- 3328578 TI - [Echoes of a great discovery. On the centenary of the introduction of rabies vaccination]. PMID- 3328579 TI - [Military hospitals in Warsaw during the November Uprising. IV]. PMID- 3328580 TI - [The origins of music therapy as a new medicinal discipline]. PMID- 3328581 TI - Cystic fibrosis in the XIX century. PMID- 3328582 TI - [Doctoral dissertations at the Purkinje School of Physiology in Breslau]. PMID- 3328583 TI - [Activities of factory hospitals in the Kingdom of Poland in the 19th century]. PMID- 3328584 TI - [Various general aspects of medical education in Germany in the 19th and 20th centuries]. PMID- 3328585 TI - [The pill doctors. The pill as a form of clinical treatment in the second half of the 19th century]. PMID- 3328586 TI - [Dr. Alexander Rytel (1896-1984)]. PMID- 3328588 TI - [Soviet medical anthropology over the last 70 years]. PMID- 3328587 TI - [A method for the azure toning of black-and-white slides]. PMID- 3328589 TI - [The evolution of chemoreception]. PMID- 3328591 TI - [Structural interrelations of the air-blood barrier and terminal sections of the lymphatic link in the pulmonary microcirculatory bed in chronic hypervolemia]. AB - The interalveolar septa of the human lungs are known to have no lymphatic capillaries. The topography of the pulmonary lymphatic system origin under conditions of chronic hypervolemia is still not investigated. Lungs of 24 corpses of persons, died from non-pulmonary pathology (control) and lungs of 34 corpses of persons, died from congenital and acquired heart disease accompanied with pre- and postcapillary forms of the pulmonary circulation hypertension, have been investigated. Decreased efficiency of the microcirculation, increased permeability of the blood capillary walls against the background of hypoxia result in an elevated production of lymph. Intensified collagen formation in the blood vessel walls and in the interalveolar septa is the prerequisite for reorganization of the pulmonary lymphatic bed. Lymphatic capillaries are found to grow into some sclerotic interalveolar septa and into deep structures of the blood capillary walls. This demonstrates a high plasticity of the lymphatic link terminal parts of the microcirculatory bed in pathologically changed lungs. PMID- 3328590 TI - [Age-related characteristics of capsular angioarchitectonics of large human joints]. AB - Angioarchitectonics of 127 capsules of large joints in superior (brachial, ulnar, radiocarpal) and inferior (coxofemoral, genicular, talocrural) extremities have been studied using a complex of anatomical and histological techniques and morphometry. As demonstrate the investigations, in the fibrous and synovial membranes of the capsules in these joints, there are certain differences in the architectonics and in depth of the blood network arrangement. In accordance with the diameter of these vessels, density and character of distribution in the capsule membranes of the joints, it is possible to distinguish four circulatory networks. They have numerous anastomoses and form a united volumetric network of vessels. Certain general regularities are noted in the structure of the vascular networks of the capsule membrane in the extremity joints, as well as changes of their angioarchitectonics are revealed as adaptations to age morphofunctional changes in the connective tissue formations of the capsules. PMID- 3328592 TI - [Therapeutic pathomorphosis of bone tumors]. AB - A comparative study of therapeutic pathomorphosis of bone tumors has shown that radiosensitive and radioresistant tumors differ in the time-course and nature of radiation-induced pathomorphosis. In radiosensitive tumors, the resultant changes arise earlier, are more strongly marked, and, as a rule, necrosis of the tumor with its replacement with fibrous tissue is observed. In radioresistant tumors, signs of radiation pathomorphosis appear later, "therapeutic giants" are typically seen to appear, and the direction in which tumor cell differentiate may change. PMID- 3328593 TI - [Theory and practice of the morphometry of human tumors]. AB - It is stated that if adequate qualitative and quantitative knowledge of tumor development is to be gained, a systems approach must be used, in which a given process is considered as representing the sum total of hierarchically organized and interrelated parts, and that quantitative data on processes of tumor development are needed for cognitive, diagnostic, evaluative, and prognostic purposes. PMID- 3328594 TI - [Bihormonal apudoma of the pancreas]. AB - A pancreatic tumor that displayed bihormonal activity is described: the tumor elaborated insulin, resulting in a hyperinsulinism syndrome (spontaneous hypoglycemia) as well as a second hormone, apparently gastrin or a gastrin-like polypeptide, which led to the development of Zollinger-Ellison syndrome. The presence of these two syndromes complicated both the diagnosis and treatment of the disease. A histologic examination using an argyrophilic (Grimelius) reaction confirmed that the tumor had originated from endocrine cells of the gastrointestinal tract and was a bihormonal apudoma of the pancreas. PMID- 3328595 TI - [Intestinal metaplasia and stomach cancer]. AB - Foci of intestinal metaplasia of gastric mucosa are known to be heterogeneous both morphologically and functionally, and several types of such metaplasia are now recognized. However, different authors use different criteria for their identification and, moreover, evaluate the signs of metaplasia in different ways. Also, the relationship of different types of intestinal metaplasia to one another and to dysplastic changes in the epithelium and to gastric cancer is a matter of controversy. Variants of intestinal metaplasia with sulfomucin secretion are considered as precancerous states that may give rise to gastric cancer of an intestinal type. PMID- 3328596 TI - [Left ventricular pseudoaneurysm. Report of a case and review of the literature]. PMID- 3328598 TI - [Pharmacological aspects of calcium channel blockers: therapeutic implications]. PMID- 3328597 TI - [Biochemical bases of platelet activity in hemostasis and thrombogenesis. II]. PMID- 3328599 TI - [Multicenter studies for evaluating the surgical treatment of coronary disease: what do they mean for the practitioner?]. PMID- 3328600 TI - [Smoking and circulatory system diseases]. PMID- 3328602 TI - [Is it worth treating mild hypertension with drugs?]. PMID- 3328601 TI - [Biochemical bases of platelet activity in homeostasis and thrombogenesis. III]. PMID- 3328604 TI - [The myocardial bridge]. PMID- 3328603 TI - [Valsalva's maneuver: mechanisms and clinical applications]. PMID- 3328605 TI - The effects of surface roughness and surface area on the retention of crowns luted with zinc phosphate cement. PMID- 3328606 TI - Strategies for cancer prevention. PMID- 3328607 TI - Antibacterial chemotherapy. Part One. B-lactam antibiotics. PMID- 3328608 TI - Lupus and non-lupus cutaneous manifestations in systemic lupus erythematosus. AB - Mucocutaneous manifestations occur frequently in systemic lupus erythematosus (SLE). Common non-lupus dermatoses may be confused with lupus rashes, with important clinical consequences. A study of 84 consecutive patients with SLE was performed to determine the comparative frequency of lupus and non-lupus mucocutaneous abnormalities, the comparative sensitivity of routine histology and immunofluorescence in the diagnosis of lupus rashes, and the association of skin manifestations with other clinical and serological features. Thirty-five patients had dermatoses attributable to SLE (mean 3.7 per patient) and 58 had dermatoses which were not directly attributable to SLE (mean 2.1 per patient), highlighting the need for accurate diagnosis of skin rashes in SLE patients. Routine histology confirmed the clinical diagnosis of typical cutaneous lupus in 100% of malar lupus rashes and in approximately 90% of subacute cutaneous and discoid lupus rashes. Direct immunofluorescence of the affected skin provided supportive evidence of cutaneous lupus in 60% of malar lupus rashes and approximately 50% of subacute cutaneous and discoid lupus rashes. This reaffirmed the poor sensitivity of immunofluorescence, compared with routine histology, in the diagnosis of lupus rashes. The association of subacute cutaneous lupus with anti-Ro antibodies was confirmed. PMID- 3328609 TI - Aminophylline in acute asthma. PMID- 3328610 TI - Cardiopulmonary resuscitation: new concepts and strategies. PMID- 3328611 TI - A rapid and preparative method for the separation of yeast ribosomal proteins by using high-performance liquid chromatography. AB - Ribosomal proteins from the yeast Saccharomyces cerevisiae were separated, on a preparative scale, by ion-exchange h.p.l.c. Proteins from the small and large ribosomal subunits were resolved, respectively, into 33 and 23 peaks, and most of the proteins present in these peaks were identified by using one- and two dimensional gel electrophoresis. Several of the peaks appeared to contain a single protein uncontaminated by other species. Ribosomal proteins were also separated by using reverse-phase h.p.l.c. Analysis of the peaks resolved indicated that the order of elution for the proteins of both ribosomal subunits is, in certain cases, different for each of the two h.p.l.c. techniques used. Thus a combination of the two chromatographic methods employed here has the potential to facilitate the rapid and preparative separation of each of the proteins present in yeast ribosomes. PMID- 3328614 TI - Quinolones: a review. PMID- 3328615 TI - Cardiac rehabilitation: an overview. PMID- 3328613 TI - Epidermal growth factor, but not insulin, stimulates tyrosine phosphorylation of an endogenous protein of Mr 95,000 in triton extracts of human placental syncytiotrophoblast membranes. AB - 1. Triton extracts of syncytiotrophoblast membranes were incubated with [gamma 32P]ATP, MgCl2 and MnCl2. Addition of epidermal growth factor (EGF) resulted in increased phosphorylation not only of the EGF receptor and a Mr-35,000 protein as previously described, but also a protein of Mr 95,000 on both tyrosine and serine residues. In addition, a small increase in the phosphorylation of a protein of Mr 105,000 was observed. Spermine had a similar effect on the phosphorylation of the Mr-95,000 protein, without affecting the phosphorylation of the other proteins. In the absence of MnCl2, the effect of spermine on the phosphorylation of Mr 95,000 protein was still evident, whereas that of EGF was greatly diminished. 2. The Mr-95,000 protein bound poorly to wheat-germ-lectin-Sepharose and was not precipitated by antisera specific for insulin and EGF receptors. The protein continued to exhibit serine and tyrosine phosphorylation on addition of [gamma 32P]ATP, MgCl2 and MnCl2 to a glycoprotein-depleted fraction prepared by chromatography on wheat-germ-lectin-Sepharose. The extent of phosphorylation was no longer increased by spermine or EGF, but was inhibited by heparin. 3. It is suggested that the Mr-95,000 protein not only is a possible direct substrate for the EGF-receptor (but not the insulin receptor) tyrosine kinase but is a substrate for other endogenous kinases, including a protein tyrosine kinase which is probably not a glycoprotein, and a protein serine kinase with properties similar to those of casein kinase II. PMID- 3328616 TI - Surgery of coronary artery disease. I). Historical notes. PMID- 3328612 TI - Effects of prolonged elevation of plasma adrenaline concentration in vivo on insulin-sensitivity in soleus muscle of the rat. AB - 1. Prolonged elevation of the plasma adrenaline concentration was produced in rats by implantation of adrenaline-releasing retard-tablets. With this technique, a hyperadrenalinaemic state is maintained for at least 5 days. 2. At 6 h after implantation of the retard-tablet it was found that plasma glucose and fatty acid concentrations increased and insulin concentration decreased compared with values obtained from placebo-tablet-implanted rats. Administration of a subcutaneous glucose load demonstrated an impaired glucose tolerance in vivo, and incubation of soleus muscle strips from 6 h-hyperadrenalinaemic rats in vitro demonstrated a decreased sensitivity of the rates of glycolysis and glucose transport to insulin. 3. The sensitivities of the rates of glycolysis, glucose transport and glycogen synthesis to insulin were determined for the incubated soleus muscle preparation isolated from animals after 48 h, 72 h and 120 h duration of hyperadrenalinaemia. At 48 h after retard-tablet implantation, the sensitivity of the processes of glucose transport and glycolysis was decreased; at 72 h, the insulin-sensitivities of the rates of glycolysis and glucose transport in skeletal muscle were similar to those determined for control animals; at 120 h, however, the sensitivities of the processes of glucose transport and glycolysis were both statistically significantly increased. In contrast, no changes in the sensitivity of the process of glycogen synthesis were observed at any of the time intervals studied. 4. The possible biochemical basis for the observed changes in skeletal-muscle insulin-sensitivity with prolonged hyperadrenalinaemia is discussed. PMID- 3328617 TI - [The practice of modern medicine and the concept of risk management]. PMID- 3328620 TI - Design principles and clinical possibilities with a new generation of radiation therapy equipment. A review. AB - The main steps in the development of isocentric megavoltage external beam radiation therapy machines are briefly reviewed identifying three principal types or generations of equipment to date. The new fourth generation of equipment presented here is characterized by considerably increased flexibility in dose delivery through the use of scanned elementary electron and photon beams of very high quality. Furthermore the wide energy range and the possibility of using high resolution multileaf collimation with all beam modalities makes it possible to simplify irradiation techniques and increase the accuracy in dose delivery. The main design features are described including a dual dipole magnet scanning system, a photon beam purging magnet, a helium atmosphere in the treatment head, a beam's eye view video read-out system of the collimator setting and a radiotherapeutic computed tomography facility. Some of the clinical applications of this new type of radiation therapy machine are finally reviewed, such as the ease of performing beam flattening, beam filtering and compensation, and the simplification of many treatment techniques using the wide spectrum of high quality electron and photon beams. Finally the interesting possibility of doing conformation and more general isocentric treatments with non-uniform beams using the multileaf collimator and the scanning system are demonstrated. PMID- 3328618 TI - [Public relations as an instrument in risk control]. PMID- 3328619 TI - [Acardiac monster: acardius mylacephalus]. PMID- 3328622 TI - Pain relief after inguinal herniorrhaphy. Ineffectiveness of pulsed electromagnetic energy. PMID- 3328623 TI - Dr. Arthur M. Sackler. PMID- 3328621 TI - [Pathophysiology and treatment of ruptured cerebral aneurysm]. PMID- 3328625 TI - Hyponatraemia associated with diuretics. PMID- 3328624 TI - Insertion technique, the key to avoiding infusion phlebitis: a prospective clinical trial. PMID- 3328626 TI - A critique of the methods used to assess leucocyte behaviour. AB - Methods for assessing the adhesive and locomotory properties of leucocytes are reviewed critically and a suggestion made as to the best strategy for testing an unknown compound on leucocyte behaviour. In particular the distinction is made between reductionist assays, where a single property is being investigated, and realistic assays where an attempt is made to mimic the situation in vivo. The realistic assays are often difficult (or impossible) to interpret in behavioural terms, because more than one cell activity is involved, but such assays (e.g. simple Boyden chambers), used with caution, may be preferable for initial screening, If effects are obvious in an assay of this type then more complex reductionist assays, to determine the cause of the altered behaviour, can be tried. In discussing adhesion, data from a flow-chamber system is presented to show the very rapid changes in adhesiveness when cells encounter an immune complex-coated surface. A fully automated tracking system for obtaining speed and persistence parameters for neutrophils is described, and some of the problems involved in estimating these parameters are illustrated. Movement of neutrophils in collagen gels provides a more realistic model of the environment in which they must operate in vivo, and the effects of incorporating immune complexes into such gels are reported. PMID- 3328627 TI - Shape, movement and function of neutrophil granulocytes. AB - Evidence that distinct types of shapes and movement can be induced by different neutrophil-activating agents like the chemotactic peptides and PMA is reviewed. Front-tail polarity seems to be preferentially associated with locomotion, whereas non-polar cells with surface projections show preferentially pinocytosis. The following partially hypothetical concept on neutrophil shape changes has been derived from these experiments: Neutrophils are capable to perform distinct types of movements depending on the stimulus or stimuli. Distinct movements are preferentially associated with distinct functions such as locomotion, pinocytosis or others. The underlying cytoskeletal changes may differ accordingly. PMID- 3328628 TI - Chemotactic activity of aldehydes. Structural requirements. Role in inflammatory process. AB - The lipid peroxidation product 4-hydroxy-2,3-transnonenal (HNE) and its homologous compounds were found to induce a high significant stimulation of rat neutrophil oriented migration and morphological polarization at concentrations within a pico-micromolar range. These effects are weak with respect to the potent chemoattractant formyl-peptides. The structural requirements for the chemotactic activity of aldehydes were studied and the trans C-C double bond was found to be the essential requirement. The problem of the mechanism by which alpha, beta unsaturated aldehydes interact with neutrophils is unsolved. With regard to this point, some hypotheses are discussed. The possibility that chemotactic unsaturated aldehydes are present in vivo in the inflammatory site at a concentration at which they are chemotactic in vitro was studied. Rat pleural exudates collected 1,2,3,4 hours after a pleurisy induction were analyzed and HNE was detected both in the supernatant of exudate and in cells. Its concentration in the liquid part of the exudate increased with time, in parallel with an increase in the number of cells in the exudate. It is reasonable that this aldehyde might be formed as a consequence of lipid peroxidation reactions concomitant to the phlogistic process. The hypothesis is proposed that HNE could participate in the neutrophil recruitment in the inflammatory area. PMID- 3328629 TI - Lymphocyte locomotion "in vitro": the role of growth activators and chemoattractants. AB - Studies of lymphocyte locomotion in vitro are reviewed. This locomotion is important (a) for recirculation and the traversing of high endothelial venules in lymphoid tissue; (b) for recruitment of lymphocytes into inflammatory sites. In the latter situation, activated lymphocytes migrate more actively than resting lymphocytes. Our studies indicate that lymphocyte activators such as PHA, anti CD3 antibodies, or the Cowan staphylococcus confer locomotor capacity on populations of human blood lymphocytes which, in the resting state, are immotile. Locomotor capacity is acquired in the G1 phase of growth and requires protein and RNA synthesis but not DNA synthesis. Anti-CD3-driven locomotor activation is inhibited by cyclosporin A, suggesting that new gene expression is required. The mitogens do not act directly as locomotor stimulants, i.e. they are not themselves chemotactic or chemokinetic factors. Rather they activate the potential for motility of lymphocytes and also cause release of lymphokines which are the direct stimulants for locomotion. One of these lymphokines (lymphocyte chemotactic factor: LCF) has been partially characterized. PMID- 3328630 TI - Locomotion of tumor cells as an element of invasion and metastasis. AB - Malignant tumor cells are endowed with the ability to invade host tissues and to produce metastases. In this review, tumor cell locomotion as an important pathogenic mechanism in the invasive process is discussed. The traffic of neoplastic cells along preformed or newly created tissue pathways will not only depend on cellular cues and/or extracellular stimulatory or inhibitory soluble factors, but also on the interactions of tumor cells with the invaded tissue. Normal tissue exerts its influence on tumor cell migration mainly by providing contact surfaces, as both the growth and locomotor phenomena of tumor cells depend on the cells ability to adhere to structures present along the invasion front. Migrating tumor cells are morphologically characterized by a cell shape change typical for locomoting cells, i.e. polarization. This locomotor phenotype is associated with altered functions of the cytoskeleton induced by agents acting on cell surface receptors, on the signal cascade, or on the cytoskeletal apparatus itself, or evoked by mutations of cytoskeletal proteins. The search for stop signals of tumor cell locomotion is of particular interest, as this may represent an approach to exert an influence on the invasive process. PMID- 3328632 TI - Cardiovascular toxicity and tricyclic antidepressants. AB - This article reviews the cardiovascular effects of the standard tricyclic antidepressants and what is known of the cardiovascular effects of the newer antidepressants. The cardiovascular effects of the standard tricyclics are orthostatic hypotension, conduction delay and a potent antiarrhythmic effect. Patients who have congestive heart failure and are on cardiac medications are at greatly increased risk for orthostatic hypotension, while patients who have pre existing conduction delay are at risk for heart block. PMID- 3328631 TI - Clinical aspects of neutrophil locomotion disorders. AB - Cellular locomotion is a crucial function for conditioning the arrival to and the behavior of neutrophils in the inflammatory site. It can be spontaneous or stimulated by chemical agents, along chemical gradient (chemotaxis) or in absence of a gradient (chemokinesis). The availability of in vitro and in vivo assays has permitted the definition of specific congenital and acquired neutrophil abnormalities, which are associated with defective host resistance. The appreciation of complex and often adverse effects of certain systemic diseases and drugs on neutrophil locomotion as well as the use of new approaches to therapy suggest the importance of assessing the role of the neutrophil in states of impaired host defense. PMID- 3328634 TI - Importance of convection to the enhancement of erythrocyte sedimentation rates in inclined tubes. AB - Erythrocytes were settled from whole blood in standard 200 x 2.5 mm erythrocyte settling rate tubes placed vertically and at various angles from 85 degrees to 15 degrees from the horizontal. In all cases sedimentation rates measured along the slope increased with decreasing angle from the horizontal. Vertical settled distances rapidly increased down to an angle of 70 degrees and then changed very little even down to angles as shallow as 30 degrees. Evidence is presented that convection plays a significant role in the inclined settling of erythrocytes, as has already been demonstrated with clay, or glass bead suspensions in water. Inclined settling enhancements obtained are quite similar to those observed under similar conditions with yeast cells in aqueous glucose. PMID- 3328633 TI - Neurochemical actions of ethylketocyclazocine and ketocyclazocine in different regions of rat brain. AB - The effects of ethylketocyclazocine (EKC) and ketocyclazocine (KC), benzomorphan derivatives proposed as kappa opioid receptor agonists, were studied by measuring changes in the levels of dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT), and their major metabolites, DOPAC, HVA, MHPG-SO4, 5-HIAA, in different regions of rat brain. Doses ranging from 1 to 10 mg/kg were tested. EKC decreased the levels of DOPAC and HVA in striatum, and increased DA concentrations, EKC markedly increased the levels of MHPG-SO4 in hypothalamus, but not in cortex, midbrain and pons-medulla. There was a non-significant decrease in NA concentrations. EKC increased the levels of 5-HIAA in hypothalamus and also in cortex, midbrain and pons-medulla, while the levels of 5-HT were increased. On the whole, similar neurochemical effects were observed after KC administration. These data were discussed in relation to the behavioral actions caused in rats by EKC and KC, including the increase in food intake, and they raise the possibility that the hypothalamic noradrenergic system participate in feeding behavior of these drugs. PMID- 3328635 TI - Such is military: Dr. George Martin Trowbridge's letters from Sherman's Army, 1863-1865. PMID- 3328636 TI - Charleston, South Carolina, 1824-1839: an early town and gown medical battle. PMID- 3328637 TI - AIDS-related psychiatric disorder. AB - The background to HIV infection, its mode of transmission, and its neurological and psychiatric complications are described. The management of AIDS-related psychiatric disorder and problems encountered among staff involved in the management of patients suffering from AIDS are considered. There is a need for appropriate educational programmes. Although the incidence of AIDS in the UK has been appreciably lower than in many other countries, there are no grounds for complacency; psychiatric disorder associated with HIV infection will be encountered much more frequently in the future. Psychiatric staff are urged to inform and prepare themselves in anticipation of this development. PMID- 3328638 TI - Marital problems and treatment outcome in depressed women. A clinical trial of social work intervention. AB - In a clinical trial investigating the effectiveness of social work intervention with depressed women patients in general practice, 80 women were randomly allocated to an experimental group for referral to attached social workers or to a control group for routine treatment by their GPs. They were reassessed at 6 and 12 months. The results indicated that women who had major marital problems were more likely to be depressed at follow-up than those with good relationships. However, patients with marital difficulties in the experimental group made more improvement than the controls. Women initially assessed as suffering from 'acute on chronic' depression and having major marital difficulties were found to benefit most from social work intervention. PMID- 3328639 TI - Mental handicap and double-blind trial design. PMID- 3328641 TI - Investigation of a Providencia rettgeri strain that has enterobacterial common antigen in the immunogenic state. AB - Antigenic material obtained by phenol-water extraction from Providencia rettgeri strains, Escherichia coli O:14 strains, and mutants of the E. coli O:14 strain were examined by the passive (indirect) hemagglutination technique, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and by immune blotting (lipopolysaccharide (LPS) blotting). Providencia rettgeri 965, like E. coli O:14, was demonstrated to have an enterobacterial common antigen (ECA) in the immunogenic form but, unlike E. coli O:14, it possessed characteristics of a smooth strain. Two populations of molecules were observed to occur in P. rettgeri 965 phenol-water extracts: one consisting of LPS identifiable with specific O antisera and the other of ECA molecules identifiable with E. coli O:14 antiserum or with a monoclonal antibody against ECA. PMID- 3328640 TI - Quantitative review of the effects of environmental temperature on food intake, egg output and energy balance in laying pullets. AB - 1. Data from 30 published experiments have been analysed to examine the relationships between environmental temperature and the long-term, adapted responses of laying pullets, measured as metabolisable energy intake, egg output and body weight change. Heat production was also estimated indirectly from the other three variables. 2. The majority of experiments employed White Leghorns, but there were 8 large trials in which brown crossbred pullets had been compared directly with White Leghorns. These trials were used to estimate differences in energy intake and heat output between brown and white birds. 3. A total of over 26,000 birds was involved in the analysis. Individual trials varied in scale from 9 birds to 2,280 birds per treatment and in duration from 8 to 61 weeks. The constant temperatures investigated ranged from 10 degrees C to 34 degrees C, but there were no data for brown pullets beyond 30 degrees C. 4. The relationship between temperature and metabolisable energy intake is curvilinear, with food intake declining more steeply as ambient temperature approaches body temperature. Adapted heat production per bird is also a curvilinear function of temperature, tending towards a value of zero when extrapolated to the point at which ambient temperature equals normal body temperature. However no satisfactory data are available for fully adapted responses in the range 34 to 42 degrees C because egg production declines continuously when these temperatures are maintained for long periods. 5. When energy intake and heat output are expressed as functions of metabolic body size (kg 0.75) they can be represented as linear functions of temperature within the range 15 to 30 degrees C, but the slope must change outside this range. 6. It is calculated that the energy available for production is at a maximum at 23 degrees C for brown birds and at 24 degrees C for White Leghorns. Gross energetic efficiency is at a maximum at 30 degrees C, but egg output is reduced at this temperature. The optimum operating temperature for laying houses will depend upon the local cost of modifying ambient temperature and on the cost of supplying diets of appropriate protein content. PMID- 3328642 TI - Effect of chlorine injury on heat-labile enterotoxin production in enterotoxigenic Escherichia coli. AB - Heat-labile enterotoxin (LT) production was examined in chlorine-injured and noninjured populations of enterotoxigenic Escherichia coli (ETEC) by passive immune hemolysis and Y-1 mouse adrenal tumor cell assays. Sublethally injured populations showed reduced LT production after 1, 2.5, and 4 h incubation in trypticase soy broth plus 0.25% glucose, pH 8.0. Reduction was observed during injury, resuscitation, and for at least 1.5 h following repair. LT levels comparable with that present in noninjured cells were found after 24 h incubation in the same medium, indicating delayed toxigenesis rather than permanent damage. Chlorinated populations failed to incorporate [14C]glucose until repair was completed suggesting a possible explanation for delayed toxin production. The results indicate a temporary loss of virulence among sublethally injured ETEC in chlorinated waters. PMID- 3328643 TI - History of dermatologic surgery. From the beginnings to late antiquity. AB - We stop short, with Celsus, our glimpse of ancient dermatologic surgery in the West. As was stated at the beginning of the chapter, only a few examples and speculations are mentioned in this brief account. Much has gone unmentioned, including the contributions of great Eastern civilizations, such as ancient India, China, and Persia; the Bible; and the "ancient" inhabitants of the "new" world. We note especially the omission of the amazing ancient Hindu cosmetic operations that successfully employed rotating pedicle flaps in reconstructing amputated ears and noses. Important names before Celsus are missing from this account, especially the two Alexandrian physician-surgeons who flourished three centuries earlier--Herophilus (the Father of Anatomy) and Erasistratus (the Father of Physiology). Except for a few extant anatomic fragments, the works of Herophilus and Erasistratus are completely lost. We may with confidence, however, infer from the writings of Celsus and Galen that the brillant anatomy and physiology of the Alexandrian period made for good surgical diagnosis and practice. We must remember, too, that after Celsus' time, the slow disintergration of the Roman Empire took more than 500 years. This period of 500 years saw a number of important Roman physician-surgeons who contributed significantly with daring new operations and original surgical concepts and techniques: Heliodorus, Soranus, Rufus, Archigenes, Galen, Antyllus, Leonides, Oribasius, Aetius, Paulus, and others. The positive surgical contributions of these giants would be lost and rediscovered, many times. PMID- 3328644 TI - Nail surgery. AB - An update of recent surgical techniques as applied to the nail unit is presented. The procedures discussed touch on areas of internal medicine, oncology, biomechanics, trauma, podiatry, infectious disease, and genodermatoses. It is evident in reviewing the literature that a mushrooming of interest in the nail unit is taking place and that this structure has inherent importance in that it may involve all facets of health care. I hope that the reader will emerge from this chapter with a greater respect for the nail and will be stimulated to learn more about it. PMID- 3328646 TI - Dermabrasive surgery. State of the art. PMID- 3328645 TI - The chemical peel. AB - The spectrum of chemical peeling encompasses a diverse group of peeling agents with the ability to produce a wide range of cutaneous burns. The most spectacular peels are produced by the phenol formulas. The physician, however, is restricted in the number of potential candidates as determined by skin color and potential toxicity. While not as impressive, trichloroacetic acid peels are an excellent modality for treatment of actinic keratoses, actinic dermatitis and lentigoes. Improvement of rhytides, skin tone, and texture can be impressive. Utilization of TCA may require repetitive peeling to obtain the desired result. With the alarming increase in the incidence of severe facial solar radiation as manifested by multiple premalignant and in situ malignant lesions, therapeutic chemical peeling has become an increasingly important procedure. The dermatologic surgeon can not only eradicate the multitude of facial lesions present but also markedly diminish the incidence of new lesions. PMID- 3328647 TI - Blood flow velocity and systolic time intervals measured by pulsed Doppler ultrasound: reproducibility of measurements. AB - The reproducibility of measurements of blood flow velocity in the aorta and systolic time intervals using pulsed ultrasound Doppler was determined in 10 subjects. Measurements were made in both the ascending aorta and the aortic arch, and instant maximum as well as instant mean velocities were measured. The smallest variation was found when the maximum velocity was measured in the ascending aorta. The coefficient of variation in measurements was between 6.9% and 13.1%, when determined at intervals of 10-15 min. Again the smallest variation was when the maximum velocity was measured in the ascending aorta. The intraobserver variation was smaller than the interobserver variation (6.9% compared with 10.6%) in the ascending aorta. Both the intraobserver and interobserver variations in systolic time intervals were very small. The mean coefficients of variation were 1.7% for the pre-ejection period (PEP), 1.7% for left ventricular ejection time (LVET), 1.4% for electromechanical systole (QS2), and 2.9% for the PEP:LVET ratio. The mean values of pre-ejection period and left ventricular ejection time were 154 ms and 377 ms, which are a little longer and shorter respectively than measurements made by phonocardiography and pulse pressure monitoring, whereas QS2 was the same (531 ms). The interobserver variations were 2.6%, 2.0%, 1.4%, and 3.9% respectively. It is concluded that pulsed Doppler ultrasound is a reliable method of measuring blood flow velocity and systolic time intervals. Changes in blood flow velocity of 10-12% can be detected by this method. PMID- 3328648 TI - Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. AB - To determine the biochemical basis of abnormal diastolic properties in human dilated cardiomyopathy calcium uptake by the sarcoplasmic reticulum in ventricular homogenates of biopsy specimens from 21 patients with dilated cardiomyopathy was compared with that in nine normal controls. As a group, patients with cardiomyopathy had considerably lower calcium uptake rates (3.3(0.6) nmol.mg-1.min-1 vs 6.5(0.5) nmol.mg-1.min-1, p less than 0.01). Calcium uptake rates correlated modestly with resting haemodynamic values and significantly with plasma noradrenaline concentrations but not with plasma renin activity. These results show that sarcoplasmic reticulum function is impaired in human dilated cardiomyopathy and that this impairment is related both to the severity of haemodynamic dysfunction and to the extent of sympathetic nervous system activation. PMID- 3328649 TI - Clinical and research implications of new concepts in the assessment of cardiac pumping performance in heart failure. AB - Every cardiac pump has its own maximum performance, which denotes its pumping capability. The difference between the performance in the resting state and that at maximum is called pumping reserve. Cardiac pumping performance is therefore best quantified by its hydraulic power output. Cardiac pumping capability is predictive of the ultimate prognosis of patients in severe heart failure whereas pumping reserve is a major determinant of exercise capacity. The therapeutic efficacy of cardiotonic drugs used in the treatment of ambulant heart failure patients should be evaluated with reference to the way they alter the relation between cardiac pumping reserve and exercise capacity. PMID- 3328650 TI - Non-invasive assessment of the age related changes in stiffness of major branches of the human arteries. AB - The static mechanical properties of major branches of the human arteries (common carotid artery, abdominal aorta, femoral artery, and brachial artery) were studied in 39 subjects, aged 6-81 years, using an ultrasonic phase locked echo tracking system that allows continuous transcutaneous measurement of the diameter of the artery. The stiffness indices were calculated from the relation between systemic blood pressure and arterial diameter. With advancing age there was a significant increase in the diameter of all arteries with a reduction in percentage change in diameter. The stiffness index increased with age in all arteries; however, in the brachial and femoral arteries there was considerable variation in the individual values for a given age. The age associated increase in stiffness was statistically significant only in the common carotid artery and the abdominal aorta. Although the mechanical properties of the peripheral arteries were significantly influenced by the measuring environment, the calculated stiffness indices were less vulnerable to these stimuli in the central arteries. These results indicate that the stiffness indices of the peripheral muscular arteries are modified appreciably by vasoactive stimuli and that the mechanical properties of the deeper elastic arteries provide sufficiently reliable information about changes caused by aging and arteriosclerosis. The new ultrasonic method used appears to be suitable for this analysis. PMID- 3328651 TI - Phenotypic suppression and nuclear accommodation of the mit- oxi1-V25 mutation in isolated yeast mitochondria. AB - Phenotypic suppression by the antibiotic, paromomycin, of the mitochondrial oxi1- -V25 mutation, a mutation which arrests by premature ochre codon the synthesis of the cox II subunit, was studied in isolated yeast mitochondria competent in translation. This antibiotic is known to suppress the mutation in vivo (Dujardin et al. 1984) and allowed in vitro, at concentrations of 20-1100 micrograms per ml. the synthesis of the cox II subunit. This strongly suggests that phenotypic suppression of mit- mutations is due to the direct action of paromomycin on mitochondrial ribosomes. The effect of paromomycin bears a resemblance to the function of the omnipotent nuclear suppressor mutation R705. The nuclear suppression was expressed in isolated mitochondria; suppressor mutation influenced the structure of the mitoribosome. Therefore, it appears that mitoribosomes are indeed the common target in the phenotypical and genetic nuclear suppression of the oxi1-V25 mutation. PMID- 3328652 TI - [Textual studies of fenshu and yanshu (two kinds of mouse)]. PMID- 3328653 TI - [A survey and pharmaceutical prospects of Rabdosia species]. PMID- 3328654 TI - [Textual research on sources of yanhusuo (Corydalis spp.)]. PMID- 3328655 TI - [Antipuretic, antimicrobic action of gegen qinlian tang]. PMID- 3328656 TI - [Epithelial neoplasms of Vater's ampulla: anatomico-clinical and immunohistochemical study]. AB - 3 adenomas and 5 carcinomas of the ampulla of Vater are studied to evaluate their histogenesis and diagnostic significance of the antigen defined by the monoclonal antibody CA 19/9. In the adenomas, some dysplastic glands show a faint positivity for CA 19/9 antigen, whereas in the ampullomas this antigen is present in adenomatous residue and in well differentiated adenocarcinomatous areas. The present observations indicate that the endoscopical and macro-microscopical examinations are fundamental to evaluate the location of the ampullary neoplasia. Moreover, the immunohistochemical finding of the CA 19/9 antigen in adenomas and carcinomas suggests their histogenetic relationship, but it is not useful in their differential diagnosis. PMID- 3328657 TI - [Malignant schwannoma of the ileum: an extremely rare disease entity (presentation of a case and review of the literature)]. AB - The authors examine a case of malignant ileal schwannoma successfully treated in the Verona Surgical Clinic. They compare their experience with the data reported in the literature, confirming the extreme difficulty encountered in diagnosing the disease. Therapy is discussed, and the authors stress that, in the presence of an intestinal haemorrhage the origin of which traditional diagnostic investigations are unable to establish, one should always bear in mind the possibility of schwannoma despite its rarity. PMID- 3328658 TI - Warfarin skin necrosis treated with prostacyclin. PMID- 3328659 TI - [Restoration of masticatory function using endosseous implants following iliac crest grafting with microsurgical vascular connection. Preliminary report]. PMID- 3328660 TI - [Alfred Berndorfer 1904-1985. A piece of medical history]. PMID- 3328661 TI - ["I feel that I am gradually approaching my disintegration...". Charles V--ruler and ruled alike]. PMID- 3328662 TI - [Heterotransplantation and its effect on structure and differentiation as illustrated by the oral mucosa]. PMID- 3328663 TI - [Modified use of the myocutaneous latissimus dorsi flap for repairing defects in the oral and maxillofacial region]. PMID- 3328664 TI - [Membrane characterization of human gingival mucosa using lectin and autoantibody binding]. PMID- 3328665 TI - [Professor Dr. B. Spiessl 65 years old]. PMID- 3328666 TI - [Tumors of the scalp. Possibilities of surgical treatment and defect repair]. PMID- 3328667 TI - [Long-term results after mandibular reconstruction using a titanium mesh system]. PMID- 3328668 TI - [Bone augmentation of an atrophic mandible using a vascularized pedicled iliac crest]. PMID- 3328669 TI - In vivo administration of antibodies against type I collagen in rat: the specific accumulation in spleen. AB - [125I]-labelled rabbit antibodies against rat type I collagen and non-immune IgG were injected into rat circulation. The kinetics of their clearance and the biodistribution in different organs were studied. Both preparations showed very similar clearance rate, the kinetics fitting bi-exponential approximation with characteristic parameters t1,1/2 = 201 +/- 20 min before 320 min and t2,1/2 = 1350 +/- 450 min at times over 320 min for antibodies and 258 +/- 45 min and 890 +/- 140 min for IgG. The specific affinity of the circulating antibodies did not decrease within 24 hours. The antibodies were specifically accumulated in spleen, where their accumulation was 5-fold higher than that of non-immune IgG. Accumulation of antibodies was maximal 3 hours after the injection. The localization ratio (i.e. the ratio of the amount of the antibodies per g of tissue to that per g of blood) reached a maximum 24 hours after the injection and remained stable for 120 hours. Immunofluorescent staining of spleen sections resulted in a bright fluorescence of dense collagenous structures in the trabeculae and in the wall of the central follicular arterium, bright spot fluorescence in the marginal zone of the follicle, and diffuse fluorescence in the red pulp. These findings suggest an unusually high accessibility of collagen type I in spleen to circulating blood plasma components. PMID- 3328670 TI - Corynebacterium pyogenes mastitis outbreak in inbred heifers in a California dairy. AB - An outbreak of Corynebacterium pyogenes mastitis ("Summer Mastitis") was observed in a group of 96 heifers. The outbreak affected 8 animals, of which 7 were too young for breeding. The disease incidence was highest in calves 2 to 4 months old. Cases were observed over an initial estimated 14 day period with a further case being detected 14 days subsequently. Corynebacterium pyogenes mastitis has not been reported in calves this age. Factors postulated to influence the outbreak include the presence of large numbers of flies, intersucking of calves, and possible viral disease. PMID- 3328671 TI - Evoked potential and electroencephalographic assessment of central blindness due to brain abscesses in a steer. AB - Central blindness in a 3.5-year-old crossbred steer was evaluated by electrodiagnostic techniques. When admitted the steer was depressed, head pressed, and circled to the left. Ptosis and absence of menace response were seen with the right eye, while the left eye was normal; direct and consensual pupillary light responses were normal in both eyes. Brainstem auditory evoked potentials and electroretinograms were essentially normal. The flash visual evoked potential (VEP) was greatly reduced upon stimulation of the right eye, while no VEP peaks could be recognized after flash stimuli were presented to the left eye. The amplitude of the electroencephalogram was depressed over right occipital cortex. Multiple brain abscesses were detected on postmortem examination adjacent to the left thalamus, in the left caudal cerebrum, and right frontal cerebrum. Corynebacterium pyogenes was cultured from abscess exudate; however, no origin for the infection could be determined. Both eyes were microscopically normal. The thalamic abscesses were postulated to have produced the EEG depression. Correlations between the VEP abnormalities and the abscess locations are discussed, based on proposed central nervous system generators of the VEP. PMID- 3328674 TI - [Cardiopulmonary allotransplantation in dogs]. PMID- 3328673 TI - [Pheochromocytoma in children]. PMID- 3328672 TI - [Value of digital subtraction hepatic arteriography in the diagnosis of liver cancer]. PMID- 3328676 TI - Molecular and cellular aspects of patterning sensory neurone connections in the vertebrate nervous system. PMID- 3328675 TI - [Current status of omentum transposition to the brain in China]. PMID- 3328678 TI - [Academician Atanas Maleev--outstanding physician, scientist and organizer of medical science and public health]. PMID- 3328679 TI - [Liposomes--prospective vectors of pharmacological agents]. PMID- 3328677 TI - [Management of refractory and fulminating colitis]. PMID- 3328680 TI - Low-dose fentanyl analgesia modified by calcium channel blockers in cardiac surgery. AB - The hypothesis that calcium channel blockers can potentiate and prolong the anti nociceptive effects of opioids was tested. Forty-five men scheduled for aorto coronary bypass operation received fentanyl according to their individual demands (haemodynamics, clinical parameters). The patients were allocated at random into three groups receiving either nimodipine 1.0 microgram kg-1 min-1 (Group 1, n = 15), nifedipine 0.70 microgram kg-1 min-1 (Group 2, n = 15), or no calcium channel blocker (Group 3, n = 15). Cerebral activity was monitored using a computerized spectral analysing system before and during the operation. The total amount of fentanyl required was significantly lower in the nimodipine group than the control group (-71%, P less than 0.001), whereas the nifedipine group did not differ from the control group. Quality of intra-operative anaesthesia was comparable in the three groups with respect to clinical observations (amnesia, sweat, tears, pupils), and the post-operative course was similar in all patients as well. Cerebral activity during the nimodipine-supplemented opioid anaesthesia was higher in the faster frequency bands (13-30 Hz). Power level in the beta range was most pronounced in Group 1, whereas power in the alpha range was similar in the calcium channel-blocker groups. The major conclusion was that nimodipine but not nifedipine administration can reduce fentanyl requirements during surgical procedures without influencing the quality of anaesthesia. PMID- 3328681 TI - Epidural analgesia for post-caesarean pain relief: a comparison between morphine and fentanyl. AB - In 20 post-operative patients who had undergone caesarean section, morphine 2 mg or fentanyl 75 micrograms in 0.9% saline were given epidurally in a randomized study, to compare their effectiveness in providing post-operative pain relief and the incidence of untoward reaction. There was a faster onset of action (P less than 0.01) and the quality of pain relief was substantially better after epidural fentanyl (P less than 0.01). However, the duration of action was markedly longer after epidural morphine (P less than 0.01). There was a significantly greater incidence of urinary retention after morphine administration (P less than 0.05). It is suggested that fentanyl gives better relief of pain than morphine when given epidurally. PMID- 3328682 TI - Ketanserin and the cardiovascular response to intubation: a preliminary report. AB - Several methods of attenuating the adverse cardiovascular effects of laryngoscopy and intubation are available. The obtunding effect of ketanserin 0.5 mg kg-1 versus that of a placebo, given 5 min prior to intubation, was investigated in a randomized double-blind trial in a group of 40 patients. Blood pressure (systolic, mean and diastolic) and pulse rate were measured at 1-min intervals with an Accutor blood pressure apparatus for 5 min before and 5 min after the injection of ketanserin or placebo, as well as for 6 min after a standardized induction (thiopentone and suxamethonium), laryngoscopy and intubation. The patients who had received ketanserin had a statistically significant lower systolic blood pressure (1 and 4 min), as well as significantly lower mean and diastolic blood pressures at 1, 2, 3 and 4 min. There were no unexpected untoward side-effects. Further investigations are suggested using ketanserin as part of a multi-faceted pharmacological approach to decrease the adverse effects of laryngoscopy and intubation. PMID- 3328683 TI - Ionized calcium levels during liver transplantation. AB - Plasma ionized calcium and total calcium concentrations were measured during 26 liver transplant operations. The level of ionized calcium decreased during the early part of the operation, reaching its lowest point during the anhepatic period, but rose again after revascularization of the new liver. Calcium chloride was given with the aim of reversing these decreases, which were associated with the use of blood products preserved in citrate-phosphate-dextrose anti-coagulant containing adenine (CPD-A). Ionic hypocalcaemia is a result of intra-operative citrate loading in the presence of poor or absent (during the anhepatic phase) liver function; aggressive correction of low ionized calcium levels, especially during the early stages of the operation, is required to prevent this effect. PMID- 3328684 TI - Peri-operative blood loss and non-steroidal anti-inflammatory drugs: an investigation using diclofenac in patients undergoing transurethral resection of the prostate. AB - Peri-operative blood loss was compared in a prospective, randomized double-blind study between two groups of patients undergoing transurethral prostatectomy (TURP) under spinal (subarachnoid) analgesia: the first received the non steroidal anti-inflammatory drug diclofenac sodium, the second group received placebo. The total blood loss and the blood loss per gram of prostate resected did not differ significantly. Some 80% of patients were completely pain free at 8 and 24 h post-operation, and low pain scores recorded by the remaining 20% of patients supported the conclusion that TURP performed under spinal analgesia is not commonly associated with severe post-operative pain. PMID- 3328686 TI - Nifedipine and metoprolol in suspected unstable angina. The Holland Interuniversity Nifedipine/Metoprolol Trial. PMID- 3328685 TI - EMLA cream reduces the pain of venepuncture in children. AB - EMLA cream (eutectic mixture of local anaesthetics) was tested in a double-blind clinical trial to examine its effect on the pain of venepuncture at induction of anaesthesia in 40 children (aged 3-13 yrs). Four pain-assessment methods were used and an assessment of the technical ease of venepuncture was made. EMLA was found to reduce significantly the pain and technical difficulty of venepuncture. This study confirms that EMLA is an effective method of reducing the pain and technical difficulty of paediatric venepuncture using 25-gauge needles for induction of anaesthesia in children. PMID- 3328687 TI - Nifedipine and metoprolol in suspected unstable angina. Principles of intervention research. PMID- 3328688 TI - Nifedipine and metoprolol in suspected unstable angina. Formation of the HINT cohort. PMID- 3328690 TI - Nifedipine and metoprolol in suspected unstable angina. Data analysis. PMID- 3328689 TI - Nifedipine and metoprolol in suspected unstable angina. Treatment, observations, and outcome events. PMID- 3328691 TI - Nifedipine and metoprolol in suspected unstable angina. Planning and conduct. PMID- 3328692 TI - Nifedipine and metoprolol in suspected unstable angina. Progress monitoring and termination. PMID- 3328694 TI - [Experience in using the Anamnez-MT automated electrocardiographic unit in the polyclinic]. PMID- 3328693 TI - Can hepatocytes proliferate when transplanted into the spleen? Demonstration by autohistoradiography in the rat. AB - The aim of this work was to study hepatocyte multiplication after transplantation into the spleen, in order to apply this technique to the treatment of chronic liver disease. Hepatocytes isolated by an in situ collagenase perfusion technique in Wistar Furth rats were injected into the splenic parenchyma of three groups of syngeneic rats: controls with normal liver (group 1), 75% hepatectomies (group 2), and end-to-side portacaval shunts (group 3). The proliferation of transplanted hepatocytes was studied by autohistoradiography after the intraperitoneal administration of 0.6 microCi/g body weight of [3H]-thymidine, at 1, 3, 7 and 15 days after transplantation of hepatocytes. Significant incorporation of [3H]-thymidine by the transplanted hepatocytes during the study period was observed mostly in groups 2 and 3. The incorporation, although delayed was sustained and of greatest magnitude in the portacaval-shunted animals. The ability of transplanted hepatocytes to proliferate in the spleen, particularly after a portacaval shunt, indicates that this procedure may have therapeutic applications in the treatment of chronic liver disease. PMID- 3328695 TI - [The traditional medicine of China: its history and contemporaneity]. PMID- 3328696 TI - [Soviet medicine at the service of achieving the Great October Revolution (1917 1987)]. PMID- 3328697 TI - [Jan (Johannes) Evangelista Purkinje (on the 200th anniversary of his birth)]. PMID- 3328698 TI - [Hydramnios]. PMID- 3328699 TI - [Aleksandr Vasil'evich Nagornyi (on the centenary of his birth)]. PMID- 3328700 TI - [The respiratory center as an autogenerator and regulator of the respiratory system]. PMID- 3328701 TI - Epidemiology and risk factors for cataract. AB - Cataract is the major cause of blindness worldwide. It is a greater problem in third world countries than in the West and several attempts have been made to explain the excess in these countries. This paper provides an overview of the literature especially on studies designed to identify risk factors for cataract. There is an association between poverty and cataract and, more specifically, between cataract and a history of severe diarrhoea-dehydration. Recent results from a case-control-led study of cataract in Oxford are also presented with the quantitation of risks associated with a number of factors including diarrhoea, renal failure and diabetes. In this study an apparently protective effect of aspirin, paracetamol and similar drugs was observed. This protective effect applies to the risk associated with diabetes. PMID- 3328702 TI - Medical treatment of cataract. PMID- 3328703 TI - Penetrating keratoplasty and cataract surgery: the advantages of an extracapsular technique combined with posterior chamber intraocular implantation. AB - The results of 28 consecutive triple procedures and 33 cases of combined penetrating keratoplasty and extracapsular extraction are presented. All the eyes with the triple procedure maintained a clear graft; 77 per cent achieved an acuity of 6/12 or better. The average time before a refractive correction could be dispensed was 8.2 months, while after a combined procedure the interval was 17.4 months, although in both groups the average time until the best visual acuity was reached was similar. PMID- 3328704 TI - The correction of post-keratoplasty astigmatism. AB - The results of refractive surgery for post-keratoplasty astigmatism in 41 eyes are presented. Thirty-nine eyes regained a functional vision of 6/12 or better. Relieving incisions and compression sutures are the most useful procedures, but more than one operation may be required. PMID- 3328705 TI - Insulin secretion--the ups and downs. PMID- 3328706 TI - Glucose homoeostasis in pregnancy and lactation. PMID- 3328707 TI - Artificial enzymes. PMID- 3328709 TI - Amphiphiles in biology: Kenneth S. Dodgson Memorial Symposium. Cardiff, 31 March 1 April, 1987. Proceedings. PMID- 3328708 TI - Amphiphile orientation: physical chemistry and biological function. AB - The critical role that amphiphiles play in biology is to provide an orienting force, probably the single most important force for structural organization in living matter. It is responsible for the organization of biological lipids into the membranes that define a living cell and prevent mixing of intracellular contents with the inanimate outside world. The same force, much reduced in magnitude, is responsible for the folding of protein polypeptide chains to specific three-dimensional structures, thereby creating the multitude of enzymes of the living cell, and the proteins that traverse the cell membrane for communication between inside and outside. Study of these phenomena has a long and fascinating history, but many important questions--all at the interface between biological and physical chemistry--remain unanswered. What is the mechanism of vesiculation of phospholipid bilayers? What is the functional role of cholesterol in cell membranes? Knowing that molecular clusters are important elements in the structure of liquid water, how do we explain the smooth extrapolation of thermodynamic data from very large to very small hydrophobic interfacial areas? PMID- 3328710 TI - Perspectives on microbial surfactants. PMID- 3328711 TI - The structural roles of amphiphilic molecules. PMID- 3328712 TI - Dynamics and structure of biomembranes. PMID- 3328713 TI - Outer membranes of gram-negative bacteria. PMID- 3328715 TI - Bile salts and biliary lipids. PMID- 3328714 TI - Liposomes in vivo; conversion of liposomal cholesterol to bile salts. PMID- 3328716 TI - Lung surfactant. PMID- 3328717 TI - Human insulin: much ado about hypoglycaemia (un)awareness. AB - The biological effects, hypoglycaemic symptoms, endocrine counterregulatory responses and glucose recovery following the injection of purified porcine and human insulin preparations were compared in a number of controlled clinical investigations and prospective clinical trials. In these studies involving healthy volunteers, Type 1 (insulin-dependent) diabetic patients on continuous subcutaneous insulin infusion or intensified conventional insulin therapy and insulin treated Type 2 (non-insulin-dependent) diabetic patients, no differences with regard to biological effects, counterregulatory responses, hypoglycaemic awareness or the long-term incidence of severe hypoglycaemia between porcine and human insulin preparations were identified. These data fail to confirm any specific risk of severe hypoglycaemia attributable to the use of human insulin preparations in the treatment of patients with diabetes mellitus. PMID- 3328718 TI - Enhanced hepatic insulin sensitivity, but peripheral insulin resistance in patients with type 1 (insulin-dependent) diabetes. AB - Sensitivity to insulin in vivo was studied in 8 normal weight C-peptide negative Type 1 (insulin-dependent) diabetic patients (age 23 +/- 1 years, diabetes duration 6 +/- 2 years), and in 8 age, weight and sex matched healthy subjects, using the euglycaemic clamp and 3-3H-glucose tracer technique. Prior to the study diabetic patients were maintained normoglycaemic overnight by a glucose controlled insulin infusion. Sequential infusions of insulin in 3 periods of 2 h resulted in mean steady state insulin levels of 12 +/- 2 versus 11 +/- 1, 18 +/- 2 versus 18 +/- 2 and 28 +/- 3 versus 24 +/- 2 microU/ml in diabetic patients and control subjects. Corresponding glucose utilization rates were 2.4 +/- 0.2 versus 2.4 +/- 0.1, 2.4 +/- 0.2 versus 3.0 +/- 0.3 and 2.9 +/- 0.3 versus 4.6 +/- 0.6 mg.kg-1.min-1, p less than 0.02. Portal insulin values in the three periods were calculated to 12 +/- 2 versus 25 +/- 3, 18 +/- 2 versus 32 +/- 3 and 28 +/- 3 versus 37 +/- 3 microU/ml in the diabetic patients and control subjects using peripheral insulin and C-peptide concentrations and assuming a portal to peripheral insulin concentration gradient of 1 in diabetic patients and of 2.4 in control subjects. Corresponding glucose production rates were 2.5 +/- 0.2 versus 2.4 +/- 0.1, 1.6 +/- 0.1 versus 0.9 +/- 0.2 and 0.7 +/- 0.1 versus 0.4 +/- 0.2 mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3328719 TI - The effects of insulin-induced hypoglycaemia on cardiovascular function in normal man: studies using radionuclide ventriculography. AB - The cardiovascular effects of an intravenous injection of soluble insulin and of acute hypoglycaemia were examined in six normal male subjects using multiple gated radionuclide ventriculography. The basal left ventricular ejection fraction rose significantly from 47 +/- 3% (mean +/- SEM) to 54 +/- 3% p less than 0.01, within 5 min of the intravenous injection of insulin, and before any significant changes occurred in the blood glucose concentration. The ejection fraction subsequently rose to a peak of 72 +/- 5% coinciding with the onset of the acute hypoglycaemic reaction. This corresponded to the nadir of blood glucose and was associated with rises in heart rate, stroke volume and cardiac output. The heart rate returned to the resting value within 30 min of the acute hypoglycaemic reaction, but the ejection fraction, stroke volume and cardiac output were still elevated 90 min later. The peak ejection fraction value immediately preceded the maximal increment of plasma catecholamines released in response to hypoglycaemia. Thus, administration of intravenous insulin had a small, immediate, discernible effect on the cardiovascular system. A subsequent rise in left ventricular ejection fraction of much greater magnitude was stimulated by the development of acute hypoglycaemia, and was associated temporally with sympatho-adrenal activation. The use of radionuclide ventriculography showed that the haemodynamic changes provoked by hypoglycaemia produced a sustained effect on cardiac contractility. PMID- 3328720 TI - Effect of the enteroinsular axis on both the A- and B-cell response to arginine after oral glucose in man. AB - Studies were made on the effect of the enteroinsular axis on amino acid-induced insulin and glucagon secretion during hyperglycaemia in man. The responses of plasma immunoreactive insulin, C-peptide, and immunoreactive glucagon to arginine infusion were investigated in nine healthy subjects after induction of hyperglycaemia by an oral glucose load and by intravenous glucose infusion to produce similar glucose concentrations in the arterialised blood. The plasma immunoreactive insulin and C-peptide levels increased to higher levels after an oral glucose load than after an intravenous infusion of glucose. The incremental areas under the immunoreactive insulin and C-peptide curves during arginine infusion were significantly greater (p less than 0.01) after oral than after intravenous glucose administration. The plasma immunoreactive glucagon level was suppressed equally after oral and intravenous glucose loads. However, during subsequent arginine infusion, the plasma immunoreactive glucagon level rose more in the presence of hyperglycaemia induced by oral than intravenous glucose. The incremental area under the plasma immunoreactive glucagon curve during arginine infusion was 1.6-fold greater after glucose ingestion than after intravenous glucose infusion. These results suggest that the enteroinsular axis has a stimulatory effect on the responses of pancreatic A and B cells to arginine after oral glucose administration. PMID- 3328721 TI - Prolonged insulin resistance following insulin-induced hypoglycaemia. AB - Nineteen normal male volunteers underwent a 10-h glucose clamp study to examine the duration and mechanism of insulin resistance after hypoglycaemia. Dextrose delivery by the Biostator to maintain the target blood glucose level fell below baseline 2 h after induction of hypoglycaemia and remained suppressed for at least 7 h after insulin hypoglycaemia. Insulin secretion as manifested by C peptide levels remained suppressed for 3-4 h after insulin hypoglycaemia despite return of blood glucose to baseline by 90 min. Glucose kinetic data (3-3H glucose) performed in six of the subjects indicated that the prolonged insulin resistance was due to significantly increased hepatic glucose production and to suppressed glucose utilisation, persisting for at least 4 h after counterregulatory hormone levels had returned to normal. Post-hypoglycaemic insulin resistance as determined by dextrose delivery was markedly attenuated and the rise in hepatic glucose output totally eliminated in five hypopituitary subjects without growth hormone or cortisol responses to hypoglycaemia. We conclude that post-hypoglycaemic insulin resistance occurs in non-diabetic subjects and persists for at least 7 h following hypoglycaemia. This prolonged insulin resistance is largely related to release of growth hormone and cortisol. PMID- 3328722 TI - Serum C3 and C4 levels and complement-dependent antibody-mediated cytotoxic activity of islet cell surface antibody in type 1 (insulin-dependent) diabetic children. AB - The role of complement in the pathogenesis of diabetes was studied in 31 Type 1 (insulin-dependent) diabetic children by assaying serum islet cell surface antibody, C3, C4 and serum complement-dependent antibody-mediated cytotoxicity. Nine of 21 islet cell surface antibody-positive children were within 5 months of disease onset and showed significantly lower serum C3 and C4 levels than either 1 year later or the remainder of the islet cell surface antibody-positive children at 6-12 months after disease onset. The overall trend of all islet cell surface antibody-positive diabetic children within 1 year of disease onset was toward increased serum C3 and C4 levels as the disease progressed. Serum C4 concentration and complement-dependent antibody-mediated cytotoxicity which showed an initial negative correlation were uncorrelated 1 year later. Four children who were initially strongly islet cell surface antibody-positive but negative 1 year later also exhibited significantly higher (p less than 0.05) mean serum C4 levels after 1 year. There was a significant decrease in complement dependent antibody-mediated cytotoxicity when sera from the diabetic children were treated with either ethylene glycol tetra-acetic acid or ethylene diamine tetra-acetic acid. These data strongly suggest that complement-dependent antibody mediated cytotoxicity induced by the classical complement pathway involving an islet cell surface antibody may play an important role in the pathogenesis of Type 1 diabetes. PMID- 3328724 TI - Alberto Monroy 23 August 1986. PMID- 3328723 TI - Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals. AB - A novel peptide, islet amyloid polypeptide (IAPP), with structural resemblance to calcitonin gene-related peptide has recently been purified from amyloid deposits in an insulinoma and from islets of Langerhans. By immunohistochemical methods, using antisera to a synthetic undecapeptide of IAPP and to insulin, we show that freshly fixed islet B cells in man, guinea pig, rat, mouse and hamster exhibit strong IAPP-immunoreactivity while A cells are unreactive. In human autopsy material, all of 11 non-diabetic individuals had IAPP immunoreactivity of the islets. In comparison 8 of the 13 patients with Type 2 (non-insulin-dependent) diabetes had no IAPP immunoreactive cells. The proportion of islet cells having IAPP immunoreactivity exceeded 10% in only 1 of the 5 remaining diabetic patients while in all 13 patients substantially more than 10% of the islet cells contained immunoreactive insulin. IAPP-positive amyloid deposits were found in 20-99% of the islets in 12 of the Type 2 diabetic patients while 6 of 11 non-diabetic subjects had amyloid in 3-11% of their islets. In islets with IAPP-immunoreactive amyloid, very few IAPP-cells were seen despite a strong reaction of the B cells with antiserum to insulin. This study shows that IAPP is a normal islet B cell component and that IAPP immunoreactivity in B cells is diminished in Type 2 diabetes while IAPP is deposited as amyloid fibrils in the islets of Langerhans. Although the function of IAPP is unknown, its occurrence in the islet B cells and its structural relation to calcitonin gene-related peptide makes a hormonal nature probable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3328725 TI - Cellular mechanism of action of thyroid hormones. AB - It has emerged in the last decade that the molecular mechanism of action of thyroid hormones resembles that of steroids; thyroid hormones indeed exert their effects mainly by directly regulating gene expression, on association with specific chromatin-bound receptors. Of the two thyroid hormones, thyroxine (T4) appears to be a sort of prohormone, whereas triiodothyronine (T3) seems to be the active form; in this respect, T4-deiodination, which occurs at the level of the target tissues, may be crucial in the local homeostasis of T3. Moreover, many cellular compartments, other than the nucleus, can bind thyroid hormone, and at least some of these further sites might play some role in modulating T3 supply to the nucleus. The binding of the T3-receptor complex to chromatin is likely to regulate the structural organization of specific genes and, in some instances, of the chromatin as a whole. PMID- 3328726 TI - Induction of the five urea-cycle enzymes by glucagon in cultured foetal rat hepatocytes. AB - Foetal hepatocytes obtained from rats at different stages were cultured in order to investigate the inducibility of the five urea-cycle enzymes by glucagon and dibutyryl cyclic AMP (Bt2cAMP). When 18.5-day-old hepatocytes were cultured for 3 days with 10(-7) M glucagon, the activities of carbamoyl phosphate synthetase (CPS), argininosuccinase (ASL) and arginase were increased by 1.4-, 1.8- and 1.9 fold, respectively, as compared to controls. These effects were mimicked by 10( 4) M Bt2cAMP, but the activities of ornithine transcarbamylase (OTC) and argininosuccinate synthetase (ASS) were never changed by the addition of these compounds. Hepatocytes cultured at earlier stages were not responsive to glucagon unless dexamethasone was added simultaneously, suggesting that this steroid might induce some steps necessary for glucagon action. Bt2cAMP was effective as early as day 16.5 without requiring the presence of steroids. In addition, the effect of the cyclic nucleotide appeared additive or synergistic with that of dexamethasone. The simultaneous addition of actinomycin D did not affect the glucagon-induced increase in enzyme levels, thus suggesting a post transcriptional effect of the hormone on the foetal enzyme activities. Insulin itself did not have any effect on the basal level of the enzyme activities and had only a moderate inhibitory effect on glucagon-induced ASL activity. This slight effect of insulin is in contrast with the marked inhibitory effect of dexamethasone on this enzyme activity that we described previously. PMID- 3328727 TI - Embryonic kidney in organ culture. AB - Organotypic cultures can be used for cultivating embryonic kidney rudiments either intact or dissociated into two interacting tissue components. This allows micromanipulations that would hardly be possible in vivo. Especially beneficial is the transfilter technique in which the interacting components are cultured on the opposite sides of a porous filter membrane. This model system allows precise timing of inductive interaction and temporal correlation of various developmental events. On the other hand, the manipulations and the in vitro conditions seem to cause metabolic changes, and long-term cultivation will result in damage to the tissues due to insufficient nutrition. Induced mesenchymal cells cultivated in monolayer cultures behave differently from those in three-dimensional organotypic explants: in the former, differentiation is largely impaired whereas in the latter, development closely resembles that in vivo. Although an organ culture system can never fully mimic embryogenesis in vivo, it offers advantages over cell cultures. PMID- 3328728 TI - Intestinal tissue and cell cultures. AB - The culture of animal cells and tissues is a widely used technique in the field of cellular and molecular biology; one of the most interesting aspect being linked to the study of the mechanisms of cell differentiation. In the specific case of intestinal epithelial cells, various tissue culture technologies have proved to be important tools for the study of precise facets related to intestinal function, pathology and differentiation. Concerning this latter aspect, organ culture experiments have brought about interesting data on the hormonal or nutritional control of intestinal maturation. Nevertheless, the study of the precise mechanisms underlying epithelial proliferation and/or differentiation at the cellular level needs more adequate cell culture model systems. One of them has been described for two cell lines derived from human colonic adenocarcinomas, in which the cells can be induced to achieve enterocytic like differentiation. Up to date, none of the continuous cell lines starting from normal undifferentiated cells have allowed generation of morphological or functional enterocytic polarity. In contrast, primary cell cultures which allow maintenance of a more physiological environment for the epithelial cells like contacts with their in vivo counterparts, mesenchymal cells or extracellular matrix molecules, have proved to be promising approaches. PMID- 3328729 TI - [ECG-gated angiocardioscintigraphy in the evaluation of ischemic cardiopathy]. PMID- 3328730 TI - [Acute isolated infarct of the right ventricle with an unusual hemodynamic and electrocardiographic pattern]. AB - The Authors reports on a case of isolated infarction of the right ventricle, with electrocardiographic pattern of non-transmural anterior myocardial infarction and haemodynamic profile suggestive of important diastolic disfunction. Clinical, angiographic and haemodynamic data are discussed along with review of the literature. PMID- 3328731 TI - A new shuttle cosmid vector, pKC505, for streptomycetes: its use in the cloning of three different spiramycin-resistance genes from a Streptomyces ambofaciens library. AB - A new shuttle cosmid vector, pKC505, was constructed for the cloning of Streptomyces DNA. This vector, which can be conjugally transferred between different streptomycetes, was used to construct a genomic library from a spiramycin-producing S. ambofaciens strain. By transformation of the spiramycin sensitive S. griseofuscus with the library, three phenotypically different spiramycin-resistance genes were isolated. S. ambofaciens DNA in these clones was colinear with the chromosome, and the cloned DNA was stable in E. coli, S. griseofuscus and S. fradiae. These cosmids could be isolated easily from S. griseofuscus, an improvement over the previous shuttle cosmid vector, pKC462a [Stanzak et al., Bio/Technology 4 (1986) 229-232], which was somewhat difficult to isolate from S. lividans. PMID- 3328732 TI - High level expression of proinsulin in the yeast, Saccharomyces cerevisiae. AB - Human proinsulin (PI) has been expressed to a high level (100 mg/liter) as a human superoxide dismutase-PI fusion protein in the yeast, Saccharomyces cerevisiae. At the junction of the two proteins is a methionine residue, allowing PI to be released from the fusion by reaction with cyanogen bromide. The fusion is expressed using a regulated, hybrid promoter containing the regulatory region of the alcohol dehydrogenase II promoter and the 3' end of a glyceraldehyde-3 phosphate dehydrogenase promoter, allowing the recombinant yeast cells to be stably maintained. Production of the fusion protein is induced by growth in medium lacking a fermentable carbon source. The heterologous fusion protein is probably insoluble within the cell, since electron microscopy reveals the presence of 'inclusion bodies'. In a cell-free extract the fusion protein is also insoluble, but can be solubilized with sodium dodecyl sulfate, and cleaved with cyanogen bromide. The PI that is produced contains incorrect disulfide bonds. After sulfitolysis, the product can be easily purified, renatured, and processed to yield insulin. PMID- 3328734 TI - [Effects of high-intensity microwave irradiation after a single exposure of rats in an irradiation field]. PMID- 3328735 TI - [Planning aspects of attachment dentures]. PMID- 3328733 TI - Cloning, mapping and molecular analysis of the pyrG (orotidine-5'-phosphate decarboxylase) gene of Aspergillus nidulans. AB - We have modified the transformation procedures of Ballance et al. [Biochem. Biophys. Res. Commun. 112 (1983) 284-289] to give increased rates of transformation in Aspergillus nidulans. With the modified procedures we have been able to complement pyrG89, a mutation in the orotidine-5'-phosphate decarboxylase gene of A. nidulans, by transformation with a library of wild-type (wt) sequences in pBR329. We have recovered, by marker rescue from one such transformant, a plasmid (pJR15) that carries an A. nidulans sequence that complements pyrG89 efficiently. In three experiments, this plasmid gave an average of 1985 stable transformants/micrograms of transforming DNA. We have analyzed ten of these genetically and by Southern hybridization. In five transformants a single copy of the transforming plasmid had integrated at the pyrG locus, in one transformant several copies of pJR15 had integrated at this locus, in one transformant several copies of the plasmid had integrated into other sites, and in three transformants, the wt allele had apparently replaced the mutant allele with no integration of pBR329 sequences. Sequence and S1 nuclease protection analysis revealed that pJR15 contains a gene that predicts an amino acid sequence with regions of strong homology to the orotidine-5'-phosphate decarboxylases of Neurospora crassa and Saccharomyces cerevisiae. We conclude that this gene is the wt pyrG allele. Finally, we have compared the 5'- and 3'-noncoding sequences and intron splice sequences to other genes of A. nidulans and have mapped the pyrG locus to a region between the fpaB and galD loci on linkage group I. PMID- 3328736 TI - Automated DNA sequencing and analysis of the human genome. AB - In the past few years, striking advances have been made in automating DNA sequence analysis. Currently, efforts are underway to automate and improve DNA purification, mapping, and data processing procedures. The predictable advances in these technologies should soon place us in a position to sequence the entire human genome. The information derived from this project will have profound implications for basic biology and clinical medicine alike. PMID- 3328737 TI - X-linked genetic homologies between mouse and man. AB - X-linked genes are conserved among all mammalian species, but the organization of genes on the X chromosome varies from one species to another. This review summarizes the evidence for established gene homologies between mice and human beings. It also describes genes that are possible homologies because of their locations in the human and murine X chromosomes and similarities in the phenotypes they produce. Based on current knowledge of homologous gene location, the human and murine X chromosomes appear to contain four highly conserved segments and differ in organization by only three to four simple chromosomal rearrangements. PMID- 3328738 TI - The origins of human gene mapping. With particular reference to the contributions of J. B. S. Haldane. AB - Methods in human gene mapping, including those developed by Bell and Haldane, Morton, and the more recent ones using somatic cell fusion, restriction fragment length polymorphism (RFLP), and multipoint linkage, are briefly reviewed. PMID- 3328739 TI - Mutagenic and toxic effects of methylisocyanate (MIC) in Salmonella typhimurium. PMID- 3328740 TI - [Quality of oral hygiene and the effects of fixed orthodontic appliances on the periodontium]. PMID- 3328741 TI - The clinical nurse specialist: review of the literature 1965-1982. PMID- 3328742 TI - Graduation address. PMID- 3328745 TI - The effects of noise on histological measures of the cochlear vasculature and red blood cells: a review. AB - This paper compiles the results from seven experiments which have investigated noise exposure effects on histological measures of the cochlear vasculature and red blood cells. Two of these studies included at least two experimental conditions and all evaluated numerous histological parameters in several cochlear vessels. The combined results suggest that noise has a consistent general effect of reducing apparent cochlear blood flow as indicated by decreased RBC density, increased aggregation of RBCs, increased variability in RBC density, decreased number of RBC columns, increased vessel lumen irregularity and encroachment of perivascular cells upon the lumen wall. When considered at the level of the individual vessels, however, inconsistent results were observed. Fewer effects were noted in experiments which permitted animals to survive after the noise exposure than in those which sacrificed the animals immediately. Impulse noise resulted in more frequent vascular sequelae than did continuous noise. Further, impulse noise more frequently influenced vessels of the external wall than did continuous noise. PMID- 3328743 TI - [Intraperitoneal pancreatic segment--allograft with delayed percutaneous duct obliteration. The 1986 results]. PMID- 3328746 TI - Cardiovascular effects of physical exercise. PMID- 3328744 TI - Variation of the ferret skull (Mustela putorius furo L.) in relation to stereotaxic landmarks. AB - The ferret skull was investigated to identify reliable extracranial landmarks for stereotaxy. The skulls of 56 ferrets of both sexes were measured in a stereotaxic apparatus. Neither body weight nor an index of skull length proved to be reliable predictors of intracranial location. Sutures fused too early in life for lambda and bregma to be useful as landmarks in adult ferrets. The position of extracranial features was used to predict the position of intracranial features. For rostral intracranial features, the supraorbital processes were found to be the best predictors. Although the occipital crest was not the best predictor for posterior structures, it was the most practical. Using these landmarks, the prediction of intracranial location could be improved by more than 30%. Sexual dimorphism was found for all features examined except those nearest the interaural line. Female skulls were significantly smaller than male skulls and had less prominent sagittal and occipital crests. Males showed a substantial variation in the structures surrounding the pituitary gland. Fitches were also found to differ from albinos in having a more marked development of the sagittal crest. PMID- 3328747 TI - Primary plasma cell leukaemia. PMID- 3328748 TI - New trends in diabetic management. PMID- 3328749 TI - Peripheral vasculitis associated with falciparum malaria. PMID- 3328750 TI - An orthopedic approach to the treatment of Class III malocclusion in young patients. PMID- 3328751 TI - Ocular hypertension or early undetected glaucoma? AB - This paper reviews the diagnostic process and the utilization of specific testing procedures - including patient history, anterior chamber evaluation, intraocular pressure measurement, optic disc evaluation, nerve fiber layer evaluation, visual field evaluation, and psychophysical and electrophysiological testing - for the clinical differentiation of ocular hypertension and primary open-angle glaucoma. PMID- 3328752 TI - Postoperative osteomyelitis following implant arthroplasty of the foot: diagnosis with indium-111 white blood cell scintigraphy. AB - Many complications can occur following insertion of silicone elastomer implants into the foot. Postoperative infection may be difficult to distinguish from other conditions such as dislodgment, fracture, ectopic and heterotopic new bone formation, synovitis, and bursitis. White blood cell scintigraphy, in conjunction with the clinical scenario, may prove to be an invaluable tool in the diagnosis of postoperative osteomyelitis, subsequent to implant arthroplasties. PMID- 3328753 TI - Adhesive capsulitis of the ankle. AB - Adhesive capsulitis is a rheumatologic complication that may be encountered in the ankle joint in posttraumatic situations. The condition presents with chronic ankle pain, stiffness, and swelling. The diagnosis can be confirmed arthrographically. A report is made of a severe case that was successfully treated with arthroscopic surgery. The shortcomings of the existing literature are discussed. The authors suggest that, where applicable, arthroscopy should be utilized in the diagnosis and treatment of this condition. PMID- 3328754 TI - Vasoconstrictive agents commonly used in combination with local anesthetics: a literature review. AB - A review of the current medical literature concerning the use of various vasoconstrictive agents with local anesthetics is presented. These agents are employed in podiatry primarily for the purpose of prolonging the duration of anesthesia and surgical hemostasis. Epinephrine, phenylephrine, levonordefrin, felypressin, and norepinephrine have all been utilized in conjunction with the local anesthetics by the various medical professions. Although controversy surrounds the use of these agents, this article should assist the podiatric physician in making an informed decision. PMID- 3328756 TI - [Optimal myocardial temperature during long-time ischemic cardiac arrest induced by GIK-cardioplegia--an experimental study]. PMID- 3328755 TI - Kaposi's sarcoma. AB - Recognition of Kaposi's sarcoma and its prevalence in the lower extremities is reviewed in light of a recent association with the acquired immunodeficiency syndrome (AIDS). PMID- 3328757 TI - [Pneumothorax due to pulmonary metastasis from malignant hemangioendothelioma of the scalp--a case report]. PMID- 3328758 TI - [A case of pulmonary plasma cell granuloma in a child]. PMID- 3328759 TI - [A case of successfully operated double mitral valve]. PMID- 3328760 TI - [Two successful cases of surgical treatment of chronic traumatic aneurysm of the thoracic aorta]. PMID- 3328761 TI - [Extended endocardial resection with intraoperative mapping for drug-resistant sustained ventricular tachycardia occurring early after acute myocardial infarction]. PMID- 3328762 TI - [A case report of primary leiomyosarcoma of the heart]. PMID- 3328764 TI - [Subacute cardiac rupture following myocardial infarction--report of three cases and review of the literature]. PMID- 3328763 TI - [Extramedullary plasmacytoma of the trachea--a surgical case and review of the literature]. PMID- 3328765 TI - [A case of congenital massive hiatal hernia in adult associated with organoaxial gastric volvulus]. PMID- 3328766 TI - [An adult case of congenital esophagobronchial fistula complicated with pyothorax]. PMID- 3328767 TI - [Surgical treatment of double outlet left atrium, report of a case]. PMID- 3328768 TI - [Infected pseudoaneurysm of the ascending aorta following aortic and mitral valve replacement--a report of successful operation]. PMID- 3328769 TI - A cast preparation technique for scanning electron microscopic study of the vascular architecture of human pulp. PMID- 3328770 TI - Clinical trial of intracanal corticosteroid in root canal therapy. PMID- 3328771 TI - Enzymes for purine synthesis and scavenging in pathogenic mycobacteria and their distribution in Mycobacterium leprae. AB - Three enzymes catalysing the synthesis of four intermediates (phosphoribosylglycinamide, phosphoribosylaminoimidazole-succinocarboxamide, phosphoribosylaminoimidazole-carboxamide and AMP) in the purine biosynthetic pathway were detected in extracts of Mycobacterium microti and M. avium, even when the organisms had been grown in mice. However only one of the three enzymes, adenylosuccinate AMP-lyase (catalysing the synthesis of the last two of the four intermediates listed above) was detected in M. leprae. Phosphoribosyltransferases, which convert adenine, guanine and hypoxanthine to the corresponding nucleoside monophosphates, and adenosine kinase were the major enzymes for purine scavenging in all mycobacteria studied. In contrast to enzymes in the synthetic pathway, evidence for metabolic regulation of the purine scavenging enzymes was obtained. In particular, 20-80-fold differences in the activities of guanine phosphoribosyltransferase and adenosine kinase were observed when M. microti was grown in media with or without purines, or in mice. In M. leprae, activities of all phosphoribosyltransferases were low in comparison with activities in M. microti and M. avium (specific activity less than 2% when comparisons were made between extracts of host-grown mycobacteria). However, activity of adenosine kinase was higher in host-grown M. leprae than in host grown M. microti or M. avium. PMID- 3328772 TI - Isolation and genetic analysis of operator-constitutive mutants of the H1 operon in Salmonella typhimurium. AB - In phase-2 cells of diphasic Salmonella strains, expression of H1 is repressor, coded for by the rh1 gene. A procedure for the isolation of operator-constitutive (H1-Oc) mutants of the H1 operon is described. Using three-factor crosses between an H1-Oc H1 strain and H1-O+ H1 strains, where motility recovery via H1-phase (or phase 1) flagellation was used as the selected marker and the H1-O character was the unselected marker, the relative position of the H1-Oc site to the H1 gene was determined. A diphasic H1-Oc strain produced, in phase 2, copolymer filaments composed of H1 and H2 flagellin. PMID- 3328773 TI - The synthesis of heat-shock proteins after a decrease in translational capacity in Escherichia coli. AB - Various conditions which decrease translational capacity and enhance the synthesis of ribosomal components were analysed with respect to the synthesis of heat-shock proteins in Escherichia coli: (a) deprivation of streptomycin from a streptomycin-dependent mutant, (b) addition of tetracycline to a partially tetracycline-resistant strain, and (c) nutritional shift-up conditions. In all cases, the rate of synthesis of the heat-shock proteins DnaK, GroEL and C62.5 decreased while the synthesis of ribosomal components increased. Thus inhibition of ribosome formation or a decrease in translational capacity do not induce the stress proteins, but have the opposite effect. PMID- 3328774 TI - Proline-induced germ-tube formation in Candida albicans: role of proline uptake and nitrogen metabolism. AB - Proline-induced germ-tube formation and cell-cell aggregation in four strains of Candida albicans were completely inhibited when the pH of the medium was 5.0 or lower, whereas morphogenesis induced by N-acetylglucosamine (GlcNAc) was unaffected even at pH 4.5. The pH sensitivity of proline-induced germ-tube formation was not caused by a modulation of proline uptake, which was unchanged over the pH range 4.5-6.5. The proline uptake system was specific, constitutive and subject to ammonium repression, and only one permease was detected, with a Km of 179 microM. Cultures deprived of nitrogen in the presence of glucose were derepressed for proline uptake but the yeast-mycelial transition could not be mediated by either proline or GlcNAc. The inhibition of morphogenesis was reversed when the nitrogen starvation was relieved by the addition of ammonium ions, proline, or certain amino acids. These results indicate that the nitrogen status of the cells is critical for the morphogenesis of C. albicans. PMID- 3328775 TI - Iron uptake by the yeast Saccharomyces cerevisiae: involvement of a reduction step. AB - Among several parameters affecting the rate and amount of iron uptake by Saccharomyces cerevisiae, the oxidation state of iron appeared to be determinant. Iron presented as Fe(II) was taken up faster than Fe(III) and the kinetic parameters were different. Iron was taken up by the cells from different ferric chelates, at rates that did not depend on their stability constants, and uptake was strongly inhibited by an iron(II)-trapping reagent like ferrozine. Iron was physiologically reduced by a transplasmamembrane redox system, which was induced in iron-deficient conditions. We propose that iron must be reduced to be taken up by the cells in the same way as other divalent cations. PMID- 3328776 TI - Incineration of hazardous waste. A critical review. PMID- 3328777 TI - [Essential elements and rheumatic diseases. Physiopathologic aspects and therapeutic implications of copper, zinc and selenium]. PMID- 3328778 TI - Studies on the promoting effects of medium chain fatty acid salts on the nasal absorption of insulin in rats. AB - We investigated the promoting effect of medium chain fatty acid salts such as sodium caprylate, sodium caprate (Na C10) and sodium laurate on rat nasal absorption of insulin. Further, we studied the possible mechanism of the absorption promoting effect by fatty acid salts in terms of hemolytic activity, osmotic pressure, chelating effect and inhibition of leucine aminopeptidase activity. Na C10 exhibited the strongest absorption promoting effect on insulin among these fatty acid salts. The promoting effect of Na C10 was very rapid reaching the maximum immunoreactive insulin level within 5 min and its optimum concentration was about 1%. The amount of insulin absorbed after a nasal administration with Na C10 was about 98% of one half subcutaneous dose. The absorption promoting effect of fatty acid salts on insulin was at least in part associated with the chelating ability for calcium ions and the inhibitory action on leucine aminopeptidase activity. PMID- 3328779 TI - Characteristics of L-glutamine transport in perfused rat skeletal muscle. AB - 1. We have investigated glutamine transport in the perfused rat hindlimb using the paired-tracer isotope dilution technique. 2. Uptake of L-glutamine was stereospecific, saturable, sodium dependent, insulin sensitive and pH insensitive in the physiological range. The maximum capacity of transport (Vmax) under normal perfusate conditions at 37 degrees C, 145 mM-Na+ and in the absence of insulin was 1156 +/- 193 nmol min-1 g-1 with transport being half-maximal at a perfusate glutamine concentration of 9.25 +/- 1.15 mM. 3. The kinetics of Na+ dependence strongly suggested co-transport of Na+ and glutamine with a stoichiometry of 1:1; furthermore, Na+ activated the carrier without any change in the concentration of glutamine at which transport was half-maximal, i.e. a 'Vmax effect' rather than a 'Km effect'. 4. The characteristics of glutamine transport, especially its substrate specificity and the pattern of competitive and non-competitive inhibition of glutamine transport by other amino acids, suggest that it is mediated by a carrier or carriers for which asparagine and histidine are also suitable substrates. 5. The characteristics of muscle glutamine transport are related but distinct from those of system N identified in hepatocytes; we suggest that they are sufficiently distinct to justify the identification of a new variant of mammalian amino acid transport systems which may be identified by the symbol Nm. 6. The kinetic characteristics of system Nm are such that glutamine is likely to be the most rapidly exchanging amino acid across the muscle membrane at physiological intra- and extracellular glutamine concentrations. Its hormone and ion sensitivities are likely to be important in the physiological modulation of whole-body glutamine metabolism and also during derangements observed in disease and after injury. PMID- 3328780 TI - The role of angiotensin II in the renal responses to somatic nerve stimulation in the rat. AB - 1. Electrical stimulation of the brachial nerves at 3 Hz (15 V, 0.2 ms), in sodium pentobarbitone-anaesthetized rats whose renal arterial pressure was held constant, elicited a 26% increase in systemic blood pressure, a 15% rise in heart rate, an 11% reduction in renal blood flow, did not alter glomerular filtration rate and significantly reduced absolute and fractional sodium excretions and urine flow by 44, 49 and 31%, respectively. 2. In a separate group of rats, brachial nerve stimulation at 3 Hz increased plasma renin activity approximately 2-fold, while in animals in which the brachial nerves were not stimulated plasma renin activity did not change. 3. Following inhibition of the renin-angiotensin system with captopril or sar-1-ile-8-angiotensin II, brachial nerve stimulation resulted in similar increases in systemic blood pressure and heart rate as in the animals with an intact renin-angiotensin system but, in captopril-infused rats, did not change renal haemodynamics or urine flow while absolute and fractional sodium excretions were reduced by 20 and 25%, respectively. In sar-1-ile-8 angiotensin II-infused animals, similar nerve stimulation decreased renal blood flow by 12%, glomerular filtration rate by 7% and absolute and fractional sodium excretions and urine flow by 25, 18 and 18%, respectively. These decreases in sodium and water output were significantly smaller than those observed in animals with an intact renin-angiotensin system. 4. Stimulation of the brachial nerves increased post-ganglionic efferent renal nerve activity by 20% and the magnitude of this response was unaffected following inhibition of the renin-angiotensin system. 5. The results show that low rates of brachial nerve stimulation in the rat can increase efferent renal nerve activity and result in an antinatriuresis and antidiuresis which is dependent on the presence of angiotensin II, and appears to be due to an action of angiotensin II at the level of the kidney. PMID- 3328781 TI - The effects of frusemide, saralasin and hypotension on fetal plasma renin activity and on fetal renal function. AB - 1. In eleven chronically catheterized fetal sheep aged 124-142 days, hypotension caused by infusion of sodium nitroprusside (1.6-3.3 mg/h) and competitive antagonism of angiotensin II by saralasin (3.3 mg/h) both caused a fall in fetal urine flow (P less than 0.02 and P less than 0.05, respectively), and in sodium excretion (P less than 0.05 and P less than 0.01) because they both caused a fall in glomerular filtration rate (G.F.R., P less than 0.02 and P less than 0.01). Neither hypotension nor saralasin had any significant effect on fractional sodium reabsorption. Saralasin only caused a significant fall in systolic pressure (P = 0.05) while infusion of sodium nitroprusside caused a fall in both systolic and diastolic pressure (P less than 0.005 and P less than 0.02). 2. Frusemide (6 mg I.V) caused a marked natriuresis and diuresis (F = 24.9, P less than 0.005 and F = 30.5, P less than 0.005). This effect was maximal within 30 min. There was no change in fetal G.F.R. and there was a significant decrease in the fraction of the filtered sodium load that was reabsorbed (F = 10.44, P less than 0.0025). Fetal mean plasma renin activity (p.r.a.) rose progressively throughout (F = 9.3, P less than 0.005). When frusemide was given to fetal sheep which were hypotensive because they were infused with sodium nitroprusside, it still caused a diuresis (F = 5.73, P less than 0.025) and the fraction of the filtered sodium load that was reabsorbed decreased (F = 4.06, P less than 0.05) to a similar extent to that seen in animals given frusemide alone. On the other hand, frusemide was ineffective as a diuretic i.e. it had no effect on fractional sodium reabsorption, when given to fetal sheep which were infused with saralasin. 3. Injection of frusemide was associated with a significant rise in the diastolic pressures of hypotensive fetuses (P less than 0.05). Furthermore, when the infusion of saralasin was terminated 1.5 h after frusemide injection, blood pressure rose significantly (F = 11.19, P less than 0.0005 for systolic pressure and F = 7.15, P less than 0.005 for diastolic pressure) and p.r.a. fell (F = 4.78, P less than 0.025). 4. It is concluded that the fetal renin-angiotensin system can play a significant role in regulation of fetal blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3328782 TI - Respiratory modulation of left ventricular stroke volume in man measured using pulsed Doppler ultrasound. AB - 1. Beat-by-beat changes in left ventricular stroke volume (l.v.s.v.) with breathing were recorded in four normal subjects using pulsed Doppler ultrasound. The l.v.s.v. fell during inspiration and rose during expiration; these changes were exaggerated at high tidal volumes. 2. Respiratory changes in l.v.s.v. persisted when respiratory rate was increased to 25 breaths/min despite an associated reduction in the degree of sinus arrhythmia. 3. During relaxed breath holding, respiratory variations in l.v.s.v. ceased immediately, and on resumption of breathing a significant fall in l.v.s.v. occurred with the first inspiratory effort. 4. Inspiratory efforts against an occluded mouthpiece were accompanied by significant variations in l.v.s.v., although the magnitude of these changes was smaller than during unoccluded breathing with similar pleural pressure changes. 5. A resistive inspiratory load increased the respiratory variations in l.v.s.v. in the three subjects studied. 6. In three patients with implanted dual-chamber pacemakers set to constant heart rates, breathing was associated with larger variations in l.v.s.v. 7. In two patients who had undergone pericardectomy, the magnitude of respiratory changes in l.v.s.v. was less than in the normal subjects. 8. We conclude that inspiration directly lowers l.v.s.v. in man by a direct mechanism which is largely independent of lung volume changes, is dependent on changes in pleural pressure, and persists in the absence of sinus arrhythmia. All these results, particularly those in pericardectomy patients, are compatible with previous animal work on the anatomical and functional interdependence of right and left ventricles during breathing. PMID- 3328783 TI - Salt appetite in the pigeon in response to pharmacological treatments. AB - 1. In response to furosemide-induced sodium depletion pigeons showed a robust salt appetite. Following the 1st depletion they started to ingest 3% NaCl after a latency of 373 +/- 69 s and in 24 h they took 21.16 +/- 3.07 ml of this solution (vs. a daily mean intake of 1-2 ml prior to the depletion). 2. The appetite was selective as shown by the fact that when, after depletion, 0.34 M-CaCl2 was offered (which is equiosmotic to 3% NaCl) pigeons took just a trivial amount of it. 3. Analysis of sodium losses following the natriuretic treatment revealed that pigeons respond to sodium depletion with an excessive overconsumption of NaCl solution. In the 2 h after access to salt they took about 3 times the amount of sodium lost. 4. Repeated sodium depletions sharply reduced the latency to the ingestion of salt and produced larger intakes. However, the overall amount of salt taken in 24 h after the later depletions was very similar and statistically indistinguishable from that taken following the 1st depletion. 5. Subchronic deoxycorticosterone acetate treatment (2 mg pigeon-1 day-1 I.M.) increased daily 3% NaCl intake, but large variability was observed in the response. 4 mg pigeon-1 day-1 evoked a reliable 3% NaCl intake which was particularly marked from the 5th day of the treatment. 6. Pulse intracerebroventricular (I.C.V.) injection of purified hog renin evoked water intake within about 1 min of injection, followed (about 6 h later) by increased salt intake. In the 24 h after renin injection pigeons took 16.58 +/- 2.89 ml of 3% NaCl. On the 2nd day following injection salt intake was still higher than in controls. 7. In conclusion, our results show that pigeons respond to sodium depletion with a robust salt appetite. Moreover, salt appetite can be evoked by deoxycorticosterone acetate as well as by renin. These findings suggest that in the pigeon salt appetite may be an endocrine induced behaviour controlled by mineralocorticoids and by the renin-angiotensin system. PMID- 3328784 TI - Epidermal growth factor selectively increases maltase and sucrase activities in neonatal piglet intestine. AB - 1. Pig intestinal sucrase and maltase activities increase markedly, and lactase activity decreases, during the second week of post-natal life. Correlations noted between the time course describing these changes and that found previously to describe a decline in the ability of the pig intestine to take up macromolecules suggest that both events are subject to the same type of developmental control. 2. Injection of epidermal growth factor (EGF) into 3-day-old piglets increase sucrase and maltase activities measured 3 days later. These increases, which are not seen when measuring other hydrolase enzymes, are confined to the mid and distal regions of the small intestine. 3. Dexamethasone injected into 3-day-old piglets inhibits lactase and, on occasion, sucrase activities without affecting other intestinal hydrolases. Significant increases in sucrase and maltase activities also occur in distal intestine following injection of EGF plus dexamethasone into 3-day-old pigs. 4. Cytochemical analysis shows EGF effects on sucrase and maltase activities to be exerted in crypt and basal villus enterocytes produced post-natally. Dexamethasone inhibits lactase activity mainly by acting on mid and upper villus enterocytes produced before birth. 5. EGF appears to increase sucrase and maltase activities by extending the time during which young enterocytes continue to accumulate these enzymes in their brush border membranes. Dexamethasone appears to cause a more fundamental change in the biochemistry of older enterocytes. accompanied by an increasing ability of these cells to transport neutral amino acids through a sodium-dependent mechanism (see James, Smith, Tivey & Wilson, 1987a). PMID- 3328786 TI - [Iodine, the thyroid and the radiologist]. PMID- 3328785 TI - [Neural control mechanisms of head movements by descending pathways]. PMID- 3328787 TI - [Magnetic resonance imaging, with surface coil, of a transplanted kidney]. AB - MR appearance of the kidney transplant is evaluated on a series of 80 examinations performed on a supraconductive unit operating at 0.5 T. Normal function kidneys displayed a clearly delineated corticomedullary differentiation (CMD); the ratio between the thickness of cortex and medulla didn't exceed 0.6. The same appearance was observed in non complicated acute tubular necrosis. Complete loss of CMD was the major finding in acute rejection (74% of the cases), but it was not specific as it was also observed in chronic rejection and in acute glomerulonephritis. Cortex thickening was helpful for the detection of rejected transplants with visible CMD. The sensitivity of MR in the detection of acute rejection was 94%. Specificity of MR findings for acute rejection depended on the transplant age: it varied from 100% for examinations performed during the first 3 months after transplantation, to less than 50% for examinations of the second year. PMID- 3328788 TI - [Intra-abdominal hemangiopericytoma. Presentation of 5 cases and review of the literature]. AB - Intra-abdominal hemangiopericytomas are rare lesions, accounting of only 10% of all hemangiopericytomas. A total of five cases are reviewed: two malignant gastric lesions, two intraperitoneal malignancies, and one "benign" pancreatic lesion with a malignant hepatic recurrence. The images obtained by ultrasonographic and CT studies corresponded either to predominantly cystic or to solid lesions. Aside from the 50% of hemangiopericytomas that are malignant from the outset, the major problem with such lesions is the uncertain nature of their natural course. PMID- 3328789 TI - [Teratoma of the parotid region: an uncommon disease. Apropos of a case with review of the literature]. AB - Cervicofacial teratoma is an infrequently reported tumor that is usually diagnosed at birth and is very rarely seen after one year of age. In the case reported, an exceptional finding was a teratoma of the parotid region in an adolescent. A literature review underlines the rarity of the lesion, diagnosis being assisted by radiologic and CT scan imaging. PMID- 3328791 TI - Capsicum and capsaicin--a review: case report of the use of hot peppers in child abuse. AB - Capsaicin, the active principle of hot peppers of the genus Capsicum, exhibits broad bioactivity. It targets neuronal structures which contain substance P, clinically seen as gastrointestinal and dermatologic irritation, bronchospasm and fibrinolysis. As a research tool, capsaicin profoundly alters neurologic anatomy and function. We review the toxicity of capsaicin and comment briefly on the use of hot peppers in child abuse. PMID- 3328790 TI - [Hemodynamic effects of a new iso-osmotic contrast medium in selective left ventriculography]. AB - To evaluate the myocardial hemodynamic effects of a new iso-osmotic contrast agent (Hexabrix 160: H 16) a randomized cross-over study was performed comparing Hexabrix 160 with Sodium Meglumine diatrizoate (Radioselectan 76: R 76) in 20 patients with ischemic heart disease. H 16 produced substantially smaller (p less than 0.001) increases in heart rate (68 +/- 11 to 73 +/- 12) than R 76 (69 +/- 12 to 88 +/- 15) and smaller decreases in left systolic ventricular pressure (131 +/ 15 to 128 +/- mmHg) than R 76 (132 +/- 14 to 94 +/- 15 mmHg). Both contrast media resulted in an increase in contractility beginning three to five seconds after the onset of the injection and reached its maximum at 45 seconds. However the increases in contractility was smaller with H 16 than R 76: H 16 caused a significantly smaller (p less than 0.01) increases in V max. (0.1 CIRC/s) than R 76 (0.35 CIR/s). The hemodynamic effects of H 16 were probably in relation with the Frank-starling mechanism. The lowest variation of preload observed (left ventricle end-diastolic pressure: 12 +/- 4 to 14 +/- 5 mmHg) showed that this contrast medium appeared to behave like isotonic serum. These results suggest that H 16 may preferable for digital left ventriculography. PMID- 3328792 TI - [Anesthesia for cadaveric renal transplantation]. PMID- 3328793 TI - [Effects of a intravenous or subarachnoid PGI2 analog (OP-41483) on cerebral and spinal cord blood flow in dogs]. PMID- 3328794 TI - [Theophylline in anesthesiology II]. PMID- 3328795 TI - [History of spinal anesthesia in Japan (3)--from 1908 to 1912]. PMID- 3328796 TI - [Malignant hyperthermia]. PMID- 3328797 TI - [Present status and new developments in neonatal medicine in Japan]. PMID- 3328798 TI - [Improvement of allogeneic bone marrow transplantation and analysis of contributing factors]. PMID- 3328799 TI - [An autopsy case of acute megakaryoblastic leukemia--identification by ABC immunoperoxidase technic employing monoclonal antibody (HPL1 and HPL7) reactive with GPIIb-IIIa and GPIb]. PMID- 3328800 TI - [Oncogenes in hematopoietic malignancies and genetic diagnosis]. PMID- 3328801 TI - [Oncogenes and its products in hematopoietic malignancies]. PMID- 3328802 TI - [Trends and methods of molecular biology in hereditary hematologic diseases]. PMID- 3328803 TI - [Mechanism of tumor metastasis--cell-to-cell interaction]. PMID- 3328804 TI - [High-frequency parotid gland ultrasonography]. PMID- 3328805 TI - [IVDSA (intravenous digital subtraction angiography) in the evaluation of congenital anomalies of the great vessels in the thorax]. PMID- 3328806 TI - [Abnormal arteriovenous communications in the mesenteric vessels]. PMID- 3328807 TI - [Acute gastric dilatation after endoscopy of the esophagus]. PMID- 3328808 TI - [A case of primary leiomyosarcoma of the greater omentum]. PMID- 3328809 TI - [Characterization of masticatory EMG during movement by a locally quasi stationary processing]. PMID- 3328811 TI - High-speed high-resolution ultrasonography. PMID- 3328810 TI - [A case of constrictive pericarditis demonstrated specific changes by 99mTc cardiac SPECT]. PMID- 3328812 TI - [Role of the Red Cross in training sisters of mercy]. PMID- 3328813 TI - [Experience in the medical evacuation support of the partisan forces in World War II 1941-1945]. PMID- 3328814 TI - Molecular evolution of rodent insulins. AB - Several trees of amino acid sequences of rodent insulins were derived with the maximum-parsimony procedure. Possible orthologous and paralogous relationships were investigated. Except for a recent gene duplication in the ancestor of rat and mouse, there are no strong arguments for other paralogous relationships. Therefore, a tree in agreement with other biological data is the most reasonable one. According to this tree, the capacity to form zinc-binding hexamers was lost once in the ancestor of the hystricomorph rodents, followed by moderately increased evolutionary rates in the lineages to African porcupine and chinchilla but highly increased rates in at least three independent lines to other taxa of this suborder: guinea pig, cuis, and Octodontoidea (coypu and casiragua). PMID- 3328816 TI - The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias. AB - Genes sequences from Escherichia coli, Salmonella typhimurium, and other members of the Enterobacteriaceae show a negative correlation between the degree of synonymous-codon usage bias and the rate of nucleotide substitution at synonymous sites. In particular, very highly expressed genes have very biased codon usage and accumulate synonymous substitutions very slowly. In contrast, there is little correlation between the degree of codon bias and the rate of protein evolution. It is concluded that both the rate of synonymous substitution and the degree of codon usage bias largely reflect the intensity of selection at the translational level. Because of the high variability among genes in rates of synonymous substitution, separate molecular clocks of synonymous substitution might be required for different genes. PMID- 3328815 TI - Slipped-strand mispairing: a major mechanism for DNA sequence evolution. AB - Simple repetitive DNA sequences are a widespread and abundant feature of genomic DNA. The following several features characterize such sequences: (1) they typically consist of a variety of repeated motifs of 1-10 bases--but may include much larger repeats as well; (2) larger repeat units often include shorter ones within them; (3) long polypyrimidine and poly-CA tracts are often found; and (4) tandem arrangements of closely related motifs are often found. We propose that slipped-strand mispairing events, in concert with unequal crossing-over, can readily account for all of these features. The frequent occurrence of long tandem repeats of particular motifs (polypyrimidine and poly-CA tracts) appears to result from nonrandom patterns of nucleotide substitution. We argue that the intrahelical process of slipped-strand mispairing is much more likely to be the major factor in the initial expansion of short repeated motifs and that, after initial expansion, simple tandem repeats may be predisposed to further expansion by unequal crossing-over or other interhelical events because of their propensity to mispair. Evidence is presented that single-base repeats (the shortest possible motifs) are represented by longer runs in mammalian introns than would be expected on a random basis, supporting the idea that SSM may be a ubiquitous force in the evolution of the eukaryotic genome. Simple repetitive sequences may therefore represent a natural ground state of DNA unselected for coding functions. PMID- 3328817 TI - [Campylobacter jejuni in patients with diarrhea]. AB - In this study the stools 125 patients with diarrhea applied to Research Hospital of Medical School of Ataturk University and the stools of 69 healthy persons were investigated for gastroenteritis agents C. jejuni as well as Salmonella and Shigella. Of the zooparasiter agents protozoon and helminths were also investigated. We determined the mentioned agents in 28 of 125 patients (% 22.40). C. jejuni was isolated the most frequent cause of diarrhea with 8.80 percent. C. jejuni was isolated in high ratio from women more than men and from children more than adults. No bacterial infection agents were determined in control group but intestinal zooparasites were found with 18.85 percent. PMID- 3328818 TI - [Susceptibility of gram-negative bacilli to aminoglycosides]. AB - In this study, the antibiotic sensitivity results of some gram-negative bacilli to aminoglycosides have been presented. 704 E. coli, 152 Klebsiella, 158 Proteus, 155 Pseudomonas strains were examined. These bacilli were isolated from the clinical samples at the bacteriology lab.in Ibni Sina Hospital, between January 1986-January 1987. The percents of E. coli strains susceptible to gentamicin, tobramycin, netilmicin and amikacin were 74%, 84%, 90%, 85% respectively. The sensitivity pattern of Proteus strains to the same antibiotic at the same order was 45%, 57%, 68, 84%. On the other hand 52%, 61%, 87%, 92% of Klebsiella strains and 32%, 53%, 86%, 81% of Pseudomonas strains have been found to be susceptible to gentamicin, tobramycin, netilmicin and amikacin respectively. According to these results, the resistance of gram-negative bacilli to aminoglycosides (including amikacin) is relatively high in our hospital, but amikacin or netilmicin should be preferred to others in which cases aminoglycoside therapy is considered. PMID- 3328821 TI - [Ultrasonic echo level and histogram in thyroid disease]. PMID- 3328820 TI - [Canine orthotopic liver transplantation]. AB - For the purpose of increasing long-term survival in canine orthotopic hepatic allotransplantation, immunosuppression by mizoribine and/or cyclosporin was instituted with the following results: 1) The survival of control dogs without treatment (n = 5) was 10.0 +/- 2.9 days (Mean +/- S.E.), and the survival of dogs treated with mizoribine (n = 15) was 44.6 +/- 31.8 days. There was no statistical difference between the two groups. On the other hand, the mean survival of dogs that were initially treated with cyclosporin and were then switched to mizoribine at one to three months after transplantation reached 145.4 +/- 70.8 days. The survival rate of dogs in the cyclosporin-mizoribine group was significantly greater than that of control group (p less than 0.02); and the survival rate of the former group proved also significantly better than that of the mizoribine group at 20 days after transplantation (X2, p less than 0.05); 2) in cases of acute rejection of the allograft, a gradual increase of the serum bilirubin level with a concomitant rise of S-GPT and alkaline phosphatase was generally observed. For an accurate diagnosis, however, an assessment of the biopsy findings of the allograft is important; 3) in chronic rejection, one animal developed the selective disappearance of interlobular bile ducts, often referred to as the "vanishing bile duct syndrome"; and 4) for differential diagnosis of vascular and/or biliary tract complications, specific morphological diagnostic procedures such as vascular and/or biliary tract angiographies are needed. PMID- 3328819 TI - [Evaluation of immunosuppressive properties of fluid from healing wounds and influence of prostaglandins]. AB - In this experiment, wound fluid (WF) was obtained by subcutaneous implantation of a stainless steel mesh cylinder through a 7 cm incision in the dorsal skin of Lewis male rats. On the tenth day after implantation, the fluid in the cylinder was aspirated. The rats in the three groups were studied after receiving dermal allografts from ACI rats. The group which received daily intraperitoneal injections of WF was found to have a graft survival time twice as long as the control groups. Two other groups were studied after receiving dermal xenografts of lyophilized porcine dermis. Until the seventh day the grafts remained elastic but then began to show signs of rejection. There was no difference in graft survival time between the group receiving WF injections and the control group. Although burn wound fluid was found to have a level of PGE 139 times normal, fluid obtained from a 7 cm skin incision on the tenth post-wounding day did not have a dramatic increase in PGE. WF appears to prolong survival of allografts but not xenografts; It is possible that PGE does not play a significant role in immunosuppressive properties of WF. PMID- 3328822 TI - [Studies on placental anemia-inducing factor (PAIF)--macroscopic immunofluorescence stain for early gastric cancer using anti-AIF antibody]. PMID- 3328823 TI - [Molecular biology in the USSR during the 70th anniversary of the Great October Revolution]. PMID- 3328824 TI - [A 2-um plasmid of Saccharomyces]. AB - The review of yeast endogenous 2 micron plasmid and of some 2 micron plasmid based vectors is devoted to structure--function relationships with a particular emphasis on the stable replication control mechanisms. Some original data on possible novel plasmid encoded proteins are provided. PMID- 3328825 TI - [Structural and functional organization of the colicin operon in the ColD-CA23 plasmid]. AB - The organization of the genes involved in colicin D synthesis was studied. These are colicin, immunity and lysis genes. The nucleotide sequence of the immunity gene, its structural and regulatory regions were determined. This gene was shown to be located next to the colicin gene on the same strand and followed by the lysis gene. When colicin synthesis is induced with mitomycin C the immunity gene is transcribed from the general SOS-dependent promotor as a part of the colicin operon. However it has its own SOS-independent promotor in normal growth conditions. A high homology in amino acid sequences of Co1D lysis protein and that of Co1E1, Co1E2, Co1E3, Co1DF13, Co1A was revealed. A detailed scheme of Co1D-CA23 colicin operon structural organization is suggested. PMID- 3328826 TI - [Genetic determinants of antibiotic resistance in enterobacteria]. AB - Antibiotic resistance of enterobacterial strains from population isolated in Krasnodar region is rather often controlled by the "plasmid" genes. The conclusion is based on using the colony hybridization with [32P]-DNA fragments of plasmids, carrying the genetic determinants of antibiotic resistance, as a method for antibiotic resistance, genes screening. Kanamycin resistance in the majority of strains is coded by APH (3') II gene, streptomycin resistance by APH (3") gene, chloramphenicol resistance by CATI, sulphonilamide resistance by DHPS type II gene. Tetracycline resistance of the studied enterobacterial strains is not connected with the widespread genetic determinants of a new class tetracycline resistance. PMID- 3328827 TI - [Processes of the survival of embryonic amygdala tissue after transplantation into different parts of the brain of adult rats]. AB - Histological examination of the Nissl and Golgi stained neurons revealed that the amygdalar embryonic grafts survive in the adult rat brain. Some quantitative characteristics, such as index of the parenchymal integration, growth potential, neuronal density and vascularization index were used for objective estimation of the graft development. The qualitative and quantitative analysis have shown that the localization of the graft in the host brain is one of the main factors determining the survival success. The grafts revealed the least survival in the host cortex. The grafts which were placed in the ventricular cavity displayed better survival. Amygdalar grafts with subcortical localization gave the best results of survival. In the "good" grafts normally differentiated neurons and glial cells were observed. The ingrowth of capillaries in the grafts could be found. The Golgi impregnation revealed the formation of the common neuropile between the grafts and the host brain. Structural integration of donor and host brain tissues provides a good model for investigation not only of the functional recovery of the neural interconnections, but also of changes in the behavior controlled by amygdalar structures. PMID- 3328829 TI - Natural sesquiterpenoids. PMID- 3328828 TI - Macrophage populations associated with multiple sclerosis plaques. AB - The macrophage population within and outside plaques from eight cases of multiple sclerosis (MS) (two clinically acute, four chronic progressive and two chronic non-progressive) has been examined in fresh frozen sections with a panel of monoclonal antibodies of macrophage, monocyte and MHC class II specificity. The majority of cells in active, hypercellular plaques, and at active borders, reacted with macrophage- and class II MHC-specific antibodies, and such cells extended beyond the border between demyelinated and myelinated parenchyma. In inactive plaques such cells that reacted with macrophage-specific antibodies were sparse and reacted only inconstantly with class II MHC-specific antibodies. Macrophage heterogeneity was evident in as much as one macrophage antibody, RFD7, reacted only with perivascular and not parenchymal macrophages in most plaques, but reacted with a variable proportion of parenchymal macrophages in active plaques. It is suggested that the RFD7 antibody may identify a sub-population of acute plaques, and that its use may clarify interpretation of findings related to other inflammatory cell populations by providing greater precision of classification of active plaques. PMID- 3328831 TI - Marine natural products. PMID- 3328830 TI - Pyrrolidine, piperidine, and pyridine alkaloids. PMID- 3328832 TI - Pyrrolizidine alkaloids. PMID- 3328833 TI - Eicosanoids, plasma membranes, and molecular mechanisms of spinal cord injury. PMID- 3328834 TI - Platelet aggregation and platelet-inhibiting drugs. AB - Platelet function may cause a progression of central gray matter damage after cerebrospinal hemorrhage or trauma because of the thrombotic occlusion of injured vessels or a vasospasm induced by extravasated blood. It has therefore been suggested that antiplatelet drugs could limit the extent of the neurological lesions produced by a spinal trauma. In view of this possibility, the hemostatic functions of platelets and the mechanism of action of antiplatelet drugs are briefly reviewed. PMID- 3328835 TI - Spinal cord extracellular microenvironment. Can the changes resulting from trauma be graded? AB - It is now clear that alternatives are available to the standard method of producing spinal injury with the Allen drop technique. We have shown that small groups of animals with predictably consistent mechanical injury descriptors can now be produced for studies of this type. These groups can easily be selected to have minimal or maximal injury results, depending upon this series of mechanical descriptors. In addition, important physiological variables seem to show acute recovery patterns consistent with recovery of function in chronic animals. Since marginal injuries are likely to be more responsive to pharmacological or surgical intervention, a sensible approach would be to design studies in which animals are close to, but not at, some degree of injury from which they will spontaneously recover. Shifts of the acute physiological, chronic behavioral, or histopathological recovery curves would then indicate the potential therapeutic index of different interventions. Only in this way can significant advances be made in the selection of protocols for human trials. PMID- 3328836 TI - The multimolecular cascade of spinal cord injury. Studies on prostanoids, calcium, and proteinases. AB - Experimental spinal cord injury in animals induced by weight drop produces neurological deficit and paralysis. Correlation of the progressive morphological changes in the lesion by both light and electron microscopy with the biochemical alterations revealed ischemia, edema, hemorrhage, tissue necrosis, granular changes in axons, vesicular degeneration of myelin and axonal calcification. The biochemical pathology was that of degradation of axonal (neurofilaments) and myelin proteins (MBP and PLP) with increased activities of proteolytic enzymes and particularly the neutral proteinase. The level of total calcium increased progressively in the lesion to a peak at 8 hrs. and subsequently remained constant thereafter. The capacity of calcium for activating proteinases and lipases and fostering the degradation of axon and myelin proteins as well as the liberation of arachidonic acid required for the synthesis of prostanoids must be relevant. An increased production of prostanoids is indicated by elevation of thromboxane (TxB2), a stable metabolite of TXA2 at 1 hour after injury. The 6 keto-PG1(1)a was also increased but to a lesser extent. We suspect that the activation of arachidonic acid metabolism contributes to post-traumatic vascular injury and the progressive ischemia. These putative roles for calcium in proteolysis and lipolysis, inducing degradation of macromolecules and production of prostanoids which initiate edema, lysolecithin a myelinolytic factor and mitochondrial dysfunction in spinal cord injury are discussed. PMID- 3328837 TI - Early membrane lipid changes in laminectomized and traumatized cat spinal cord. AB - The effects of surgical exposure (laminectomy) and compression trauma on various aspects of membrane lipid metabolism in the feline spinal cord were determined in this study. Tissue samples were frozen in situ and grossly dissected into gray and white portions prior to lipid analyses. Laminectomy alone resulted in measurable changes in spinal cord lipid metabolism, including increases in gray matter free fatty acids, diacylglycerols, and eicosanoids. A 90-min recovery period greatly reduced the levels of these compounds. Compression of the spinal cord with a 170-g weight (following a 90-min recovery period) caused very large increases in gray matter free fatty acids, diacylglycerols, and eicosanoids, and decreases in cholesterol and ethanolamine plasmalogens. Similar, but time delayed changes in these compounds were also observed in white matter. PMID- 3328839 TI - Medicare payment suggestion. PMID- 3328840 TI - The Ohio Medicaid Drug Formulary. PMID- 3328838 TI - Phospholipases, lysophospholipases, and lipases and their involvement in various diseases. PMID- 3328841 TI - [Patient cooperation (compliance) in orthodontics. An overview]. PMID- 3328842 TI - [Osteo-integrated 2-phase Branemark implants. Experiments with the therapeutic concept to restore the chewing function in atrophic jaws]. PMID- 3328843 TI - [A model of genetic therapy of selected disease entities]. PMID- 3328844 TI - [Clinical trial of cimetidine in the treatment of vertigo]. PMID- 3328845 TI - [Postoperative pain]. PMID- 3328846 TI - The use of liposomes in the diagnosis and treatment of malignant disease. PMID- 3328847 TI - Familial hypocalciuric hypercalcaemia--familial benign hypercalcaemia: a review. PMID- 3328849 TI - Transient atrial fibrillation precipitated by hypoglycaemia: two case reports. AB - We describe two insulin-dependent diabetic females who presented with severe hypoglycaemia associated with atrial fibrillation which reverted to sinus rhythm after intravenous dextrose. Atrial fibrillation has not previously been reported as a complication of hypoglycaemia in insulin-dependent diabetic patients. PMID- 3328850 TI - Carcinoma of the duodenum. AB - We report two patients with primary adenocarcinoma of the duodenum who underwent successful pancreatico-duodenectomy (modified Whipple operation). One patient died from an unrelated cause three years following surgery whilst the other remains well and clinically free of disease 3 years after resection. An aggressive surgical policy in patients with this rare tumour seems justified. PMID- 3328848 TI - When to use insulin in the maturity onset diabetic. PMID- 3328851 TI - Flupirtine: the first Italian experience. AB - This paper reports the results of five single-dose short-term, controlled clinical trials conducted in Italy with the structurally new analgesic flupirtine. A total of 200 patients were enrolled in the trials. One hundred and two patients received flupirtine, 61 were treated with reference drugs (suprofen and paracetamol) and 37 were on placebo. Analgesic efficacy was evaluated in post episiotomy pain (2 studies and 70 patients), post-traumatic pain (2 studies and 100 patients) and in 30 post-operative patients. Flupirtine was given as a single dose of 100 mg (one capsule) or as a single day's treatment (100 mg t.i.d.). For suprofen and paracetamol, oral doses of 200 mg and 500 mg respectively were used. A semi-quantitative four- or five-point scale or a linear analogue scale was used to determine the degree of pain. In post-episiotomy pain, the time required to achieve a reduction of 50% of the initial pain was also used. In post-operative pain, flupirtine induced a 69% reduction in the pain score 6 hours after administration, compared with 26% in the placebo group. In post-episiotomy pain and pain due to sport injury, flupirtine showed greater efficacy as judged by the number of patients reporting good and acceptable pain relief, and a faster onset of pain relief than suprofen (episiotomy) or paracetamol plus massage (sport injury). The adverse reaction, nausea, was complained of once only during treatment with flupirtine. PMID- 3328852 TI - Pharmacology of centrally acting analgesics: an introduction. AB - Aspirin-like drugs, paracetamol and amidopyrine exert their analgesic action predominantly at the site of origin of pain, e.g. in inflamed or functionally altered tissues. Opioids are thought to inhibit processing of pain-related neuronal inputs in the CNS including the spinal cord. This hypothesis has been extended by the discovery of opioid receptors, enkephalins and endorphins and interactions of these mediators with others including substance P, serotonin and other aminergic neurotransmitters. A review of the present situation is presented focussing on possible new sites of action of centrally acting analgesics. PMID- 3328853 TI - Flupirtine in the treatment of post-operative pain. AB - Flupirtine maleate (referred to throughout this paper as flupirtine) capsules 100 mg and suppositories 150 mg were found to be safe and efficacious in several randomized, controlled, double-blind parallel group clinical trials. 586 patients (40 children) suffering from post-operative pain were treated. Flupirtine was significantly more effective than placebo and as well tolerated. It was as effective and acceptable as pentazocine and dihydrocodeine for the treatment of post-operative pain, but offered advantages in terms of fewer central nervous system side effects. It was at least as effective as the non-narcotics metamizole, paracetamol and naproxen. PMID- 3328854 TI - Clinical experience with flupirtine in the U.S. AB - Flupirtine, a chemically unique, orally effective, non-narcotic, centrally acting analgesic was evaluated for efficacy and safety in five parallel, double-blind randomized clinical trials which included both placebo and active control comparisons. Flupirtine was given in oral doses of 100 to 300 mg, with a maximum daily dose of 600 mg to patients with pain resulting from episiotomy, surgical or dental procedures. Patients rated pain intensity, pain relief and adverse experiences at regular intervals up to 6 hours following medication. Assessments of efficacy included measures of the sum of pain intensity differences (SPID), total pain relief (TOPAR) and peak analgesia (PPID). More than 1300 patients have been evaluated at 26 study sites in the United States. More than 170 of them received flupirtine 100 mg, 250 received 200 mg and 50 received 300 mg. An additional 415 patients received positive control medications (paracetamol 650 mg, codeine 60 mg, pentazocine 50 mg or oxycodone 10 mg plus paracetamol 650 mg). All doses of flupirtine produced analgesia after a single dose. Pharmacokinetic evaluations have shown linear kinetics for flupirtine and a 100 mg t.i.d. dosage schedule produces average steady-state blood levels equivalent to the peak response for a single 200 mg dose. Adverse experiences occurring in flupirtine clinical studies have been minimal in incidence, nature and degree, with drowsiness being the most frequently reported reaction (approximately 10%). PMID- 3328855 TI - Assessment of analgesia by evoked cerebral potential measurements in humans. AB - This paper gives a brief account of new methods for the evaluation of pain and analgesia in healthy male volunteers by use of evoked cerebral potentials. In pain research, the so-called late components with latencies between 100 and 400 ms are usually used, but these potentials are non-specific, depending on a variety of factors e.g. on the activity of the ongoing electroencephalogram (EEG) on the subject's arousal/attention mechanisms, on the novelty of the stimulus and on its painfulness. Therefore, if evoked cerebral potentials in response to phasic pain stimuli are to be evaluated quantitatively, constant experimental conditions are essential, including subject selection to obtain as uniform a sample of volunteers as possible. Latency variation in evoked potential components in single studies makes signal averaging methods rather inaccurate to predict the effects of weak analgesics upon cerebral potentials in relation to time. Therefore single trial studies have been performed using transformation of post-stimulus EEG activity in terms of frequency. Because of the short duration of the evoked potentials, various parametric spectral estimators have been investigated for their advantages in EEG analysis. Frequency transformation of stimulus-induced cerebral activity by means of the maximum entropy method gives an enormous increase in the power in the 2-4 Hz frequency band with a very constantly located maximum. Examples are given showing that in this way it might be possible to monitor the time course of efficacy of even so-called weak analgesics. PMID- 3328856 TI - Dependence of lymphoma growth on 'reversed immunological surveillance'. PMID- 3328857 TI - Detection of human somatic cell structural gene mutations by two-dimensional electrophoresis. AB - The feasibility of detecting human somatic structural gene mutations by two dimensional electrophoresis has been investigated. A lymphoblastoid cell line was grown as a mass culture in the presence of ethylnitrosourea, after which cells were regrown as single cell clones. A total of 257 polypeptide spots were analyzed in gels derived from 186 clones. Four structural mutations were detected by visual analysis of the gels. Computer analysis of gels corresponding to the mutant clones was also undertaken. At a spot size threshold of 200 spots to be matched using a computer algorithm, all four mutant polypeptides were detected. These results indicate the usefulness of the two-dimensional approach for mutagenesis studies at the protein level. PMID- 3328858 TI - Subunit assembly and metabolic stability of E. coli RNA polymerase. AB - Immunological cross-reaction was employed for identification of proteolytic fragments of E. coli RNA polymerase generated both in vitro and in vivo. Several species of partially denatured but assembled RNA polymerase were isolated, which were composed of fragments of the two large subunits, beta and beta', and the two small and intact subunits, alpha and sigma. Comparison of the rate and pathway of proteolytic cleavage in vitro of unassembled subunits, subassemblies, and intact enzymes indicated that the susceptibility of RNA polymerase subunits to proteolytic degradation was dependent on the assembly state. Using this method, degradation in vivo was found for some, but not all, of the amber fragments of beta subunit in merodiploid cells carrying both wild-type and mutant rpoB genes. Although the RNA polymerase is a metabolically stable component in exponentially growing cells of E. coli, degradation of the full-sized subunits was found in two cases, i.e., several temperature-sensitive E. coli mutants with a defect in the assembly of RNA polymerase and the stationary-phase cells of a wild-type E. coli. The in vivo degradation of RNA polymerase was indicated to be initiated by alteration of the enzyme structure. PMID- 3328859 TI - Characterization of a slow folding reaction for the alpha subunit of tryptophan synthase. AB - The equilibria and kinetics of urea-induced unfolding and refolding of the alpha subunit of tryptophan synthase of E. coli have been examined for their dependences on viscosity, pH, and temperature in order to investigate the properties of one of the rate-limiting steps, domain association. A viscosity enhancer, 0.58 M sucrose, was found to slow unfolding and accelerate refolding. This apparently anomalous result was shown to be due to the stabilizing effect of sucrose on the folding reaction. After accounting for this stabilization effect by using linear free-energy plots, the unfolding and refolding kinetics were found to have a viscosity dependence. A decrease in pH was found to stabilize the domain association reaction by increasing the refolding rate and decreasing the unfolding rate. This effect was accounted for by protonation of a single residue with a pK value of 8.8 in the native state and 7.1 in the intermediate, in which the two domains are not yet associated. The activation energy of unfolding is 4.8 kcal/mol, close to the diffusion limit. The negative activation entropy of unfolding, -47 cal/deg-mol, which controls this reaction, may result from ordering of solvent about the newly exposed domain interface of the transition state. These results may provide information on the types of noncovalent interactions involved in domain association and improve the ability to interpret the folding of mutants with single amino-acid substitutions at the interface. PMID- 3328860 TI - Prediction of secondary structure by evolutionary comparison: application to the alpha subunit of tryptophan synthase. AB - The amino acid sequences of the a subunits of tryptophan synthase from ten different microorganisms were aligned by standard procedures. The alpha helices, beta strands and turns of each sequence were predicted separately by two standard prediction algorithms and averaged at homologous sequence positions. Additional evidence for conserved secondary structure was derived from profiles of average hydropathy and chain flexibility values, leading to a joint prediction. There is good agreement between (1) predicted beta strands, maximal hydropathy and minimal flexibility, and (2) predicted loops, great chain flexibility, and protein segments that accept insertions of various lengths in individual sequences. The a subunit is predicted to have eight repeated beta-loop-alpha-loop motifs with an extra N-terminal alpha helix and an intercalated segment of highly conserved residues. This pattern suggests that the territory structure of the a subunit is an eightfold alpha/beta barrel. The distribution of conserved amino acid residues and published data on limited proteolysis, chemical modification, and mutagenesis are consistent with the alpha/beta barrel structure. Both the active site of the a subunit and the combining site for the beta 2 subunit are at the end of the barrel formed by the carboxyl-termini of the beta strands. PMID- 3328861 TI - Hybrid immunoglobulin isotypes of identical specificity produced by genetic recombination in Escherichia coli and expression in lymphoid cells. AB - We have produced a series of hybrid IgG1.IgG2a mouse immunoglobulins with identical light chains (L) and variable regions to facilitate the identification of structural features associated with functional differences between immunoglobulin isotypes. Hybrid heavy chain (H) constant region gene segments were generated by genetic recombination in Escherichia coli between plasmids carrying mouse gamma 1 and gamma 2a gene segments. Crossovers occurred throughout these segments although the frequency was highest in regions of high nucleotide sequence homology. Eleven variant immunoglobulins produced by transfected hybridoma cell lines are assembled into H2L2 tetramers and properly glycosylated. In addition, all 11 immunoglobulins have identical antigen combining sites specific for the fluorescent hapten epsilon-dansyl-L-lysine. Protein A binding was used as a probe of the structural integrity of the Fc portion of these variant antibodies. Differences in protein A binding between IgG1 and IgG2a appear to be due to amino acid differences at positions 252 (Thr----Met) and 254 (Thr----Ser) of the heavy chain (EU numbering). PMID- 3328862 TI - Prediction of the tertiary structure of the alpha-subunit of tryptophan synthase. AB - The tertiary structure of the alpha-subunit of tryptophan synthase was proposed using a combination of experimental data and computational methods. The vacuum ultraviolet circular dichroism spectrum was used to assign the protein to the alpha/beta-class of supersecondary structures. The two-domain structure of the alpha-subunit (Miles et al.: Biochemistry 21:2586, 1982; Beasty and Matthews: Biochemistry 24:3547, 1985) eliminated consideration of a barrel structure and focused attention on a beta-sheet structure. An algorithm (Cohen et al.: Biochemistry 22:4894, 1983) was used to generate a secondary structure prediction that was consistent with the sequence data of the alpha-subunit from five species. Three potential secondary structures were then packed into tertiary structures using other algorithms. The assumption of nearest neighbors from second-site revertant data eliminated 97% of the possible tertiary structures; consideration of conserved hydrophobic packing regions on the beta-sheet eliminated all but one structure. The native structure is predicted to have a parallel beta-sheet flanked on both sides by alpha-helices, and is consistent with the available data on chemical cross-linking, chemical modification, and limited proteolysis. In addition, an active site region containing appropriate residues could be identified as well as an interface for beta 2-subunit association. The ability of experimental data to facilitate the prediction of protein structure is discussed. PMID- 3328864 TI - [Study of venous insufficiency in the light of ambulatory phlebectomy]. AB - Considering an ambulatory phlebectomy is, first, a thorough analysis of the venous insufficiency: visual and manual analysis, provides macroscopic informations on the varicose veins disease; superficial venous Doppler is irreplaceable to monitor the reflux and screen varicose tracts and insufficient perforators, without clinical manifestations, as well as recurrent sources if neglected; ultra-sonography and varicose veins phlebography will enlighten borderline cases; the evaluation of the results of previous treatments on the tissues (surgery, sclerosis, thrombectomy), of trophic complications (sclerous hypodermatitis, calcinosis) and of scarred or pigmented abnormalities, will permit to "evaluate the area" of this ambulatory phlebectomy. PMID- 3328863 TI - [Phlebology consultation services open to physicians]. PMID- 3328865 TI - [50 years of stereophlebography]. AB - The utilization criteria of stereophlebography since his creation by Cid dos Santos fifty years ago are analysed. During many years it was applied on all varicose and thrombophlebotic patients. At present, it is used only in cases where history, physical signs and non-invasive tests are not able to give a perfect knowledge of the situation. A replacement of the phlebography in its actual fashion in future time by some non-invasive technics like duplex-scan may be admitted. However, at present, it is still the more efficient and the most exact method for diagnosis of the venous disease of the limbs. PMID- 3328866 TI - [Value of venous ultrasonic tomography in the screening for unusual emboli causing foci]. AB - In certain cases of pulmonary embolism, phlebography of the lower extremities remains normal. The study of 219 consecutive cases of pulmonary embolism shows the advantage of venous ultrasonic tomography which, alone, enables to screen the embolic focus in 10% of the cases, either because the phlebographic data are insufficient (5%), or because the embolic focus cannot be reached with phlebography (5%), especially in deep femoral and internal saphenous thromboses. On the other hand, popliteal venous aneurysms, which represent 1% of all embolic foci in this study, are always discovered by ultrasonography. Therefore this technique appears absolutely necessary for the diagnosis of an embolic venous focus. PMID- 3328867 TI - [Role of grafts in the treatment of resistant ulcers]. AB - Despite a correction as complete as possible of the venous stasis, certain ulcers prove resistant to treatment. In these cases, grafts, whose active mechanism is still not well known in many respects, can turn out to be effective. PMID- 3328868 TI - [3 key problems. From the reminiscences of a female activist. 5]. PMID- 3328870 TI - [Trace elements in mental disorders]. PMID- 3328869 TI - Carbamazepine and physostigmine eyedrops in the treatment of early alcohol withdrawal and alcohol-related hypertension. PMID- 3328872 TI - [Psychosocial and social problems related to multiple sclerosis]. PMID- 3328871 TI - [Electroconvulsive therapy: pro's and con's in the light of the review of current literature]. PMID- 3328873 TI - DARPP-32, a dopamine-regulated phosphoprotein. PMID- 3328874 TI - The role of inositol phosphates in intracellular calcium mobilization. PMID- 3328875 TI - Structural and functional aspects of epidermal growth factor (EGF) and its receptor. PMID- 3328876 TI - Protein phosphorylation in the nerve growth cone. PMID- 3328878 TI - The role of protein kinases in the control of prolonged changes in neuronal excitability. PMID- 3328877 TI - Possible roles of protein kinase C in signal transduction in nervous tissues. PMID- 3328879 TI - Stress on personnel working in a critical care unit. AB - This article has examined individual and overall stresses on personnel working in a critical care unit. Burnout behaviors have been identified and discussed. Strategies have been outlined for identifying, adapting and alleviating stress, that have application not only to critical care units but to hospital settings in general. PMID- 3328881 TI - [Social aspects of epilepsy]. PMID- 3328880 TI - New technology: morphine pump. PMID- 3328882 TI - [The need for supplementing vitamin D and calcium in chronic diseases of the digestive system]. PMID- 3328884 TI - [John Keats--physician and poet]. PMID- 3328885 TI - [Reminiscence of Prof. Wincenty Wcislo]. PMID- 3328883 TI - [Ren sentaneus (the tortoise-shaped kidney)]. PMID- 3328886 TI - [Application of radioisotopes in the studies of glucoconjugates]. PMID- 3328887 TI - [Introduction to the experiments of genetic engineering. III. Gene library (microorganism)]. PMID- 3328888 TI - Unilateral renal arterial infusion and renal vein catheterization in rabbits. Study of renal function and renin release. AB - This study evaluates the direct effects of verapamil and furosemide infused into the unilateral renal artery on renal function and the renin secretion rate in renal vein-catheterized rabbits. Catheterization did not alter the renal function parameters of the kidney. Verapamil and furosemide increased renal blood flow, urine flow, and urinary sodium, potassium and chloride excretions confined to the infused kidney. Verapamil increased the glomerular filtration rate and free water clearance. The renin secretion rate was increased by furosemide but not by verapamil. The present study shows that the technique is applicable to renal function studies in which unilateral renal arterial infusion of the agents studied is required. The contralateral kidney can be a reliable control for the infused kidney. It also provides a useful technique for the study of renin release in rabbits. PMID- 3328889 TI - Classification of the legionellae. AB - This article reviews the classification and identification of the 23 described species, the 11 unnamed species, and the 49 serogroups presently known in the family Legionellaceae and the genus Legionella. The events leading to the isolation and classification of the first species, Legionella pneumophila, are summarized; these include the outbreak of legionnaires' disease at the 1976 American Legion Convention in Philadelphia, the five outbreaks preceding the Philadelphia outbreak, and the isolation of three Legionella species before 1976. The phenotypic characteristics of legionellae are described, including growth requirements, isolation media, biochemical tests, cellular fatty acids, quinones, and the guanine-plus-cytosine (G + C) content of DNA. Identification of legionellae by serology, monoclonal antibodies, and gene probes is described. Each species is listed with an explanation of its name, the source, location of its isolation, its involvement, if any, in human disease, its type strain, and the person who isolated it. The basis of taxonomy by DNA hybridization at the species level and evidence consistent with all species in a single genus and family are described. Problems with identification of legionellae at the species level and with their classification, especially at the genus level, are discussed. PMID- 3328890 TI - The epidemiology of Legionella pneumophila infections. AB - The study of outbreaks of Legionella pneumophila has been essential in understanding the organism, the disease, and its pathogenesis. Early epidemics defined the clinical spectrum: Pontiac fever is an acute, self-limited, febrile illness with an attack rate of 95% to 100% and an incubation period of 36 hours. In contrast, legionnaires' disease is a life-threatening bronchopneumonia with an attack rate of 2% to 7% and an incubation period of two to ten days. Three times as many males as females are affected with legionnaires' disease, and age, cigarette smoking, and chronic medical disease (particularly immunosuppression) appear to be separate risk factors. Furthermore, L pneumophila is responsible for approximately 1% to 3% of community-acquired pneumonias, 13% of those acquired in the hospital and as many as 26% of atypical pneumonias. Diverse environmental reservoirs have been identified, including cooling systems, potable or domestic water systems, respiratory therapy devices, industrial coolants, and whirlpool spas. Hot water temperature, stagnant water, sediment, and the presence of other microorganisms are important factors in the amplification of the Legionellaceae. Although airborne transmission has been widely suggested, aspiration may be an important mode in certain patients. Regional and national surveillance may identify common sources and allow the introduction of early control measures. The latter have included primarily pulse and continuous hyperchlorination and super heating hot water systems to 50 to 60 degrees C. Experimental data suggest that ozone and UV light may be useful in the future. Additionally, cooling towers and evaporative condensers have been decontaminated and maintained with a variety of biocides. The prevention of outbreaks requires thoughtful planning, redesign, and good engineering practices. PMID- 3328891 TI - Pathogenesis and pathology of legionellosis. AB - Infection with members of the genus Legionella can produce a wide spectrum of disease ranging from a self-limiting febrile illness to life-threatening pneumonia. The primary site of infection in the pneumonic form of the disease appears to be the lung, but dissemination to other organs is possible. Infection results in an intense alveolitis with infiltration by large numbers of mixed inflammatory cells. The legionellae are facultative intracellular pathogens which multiply within host phagocytic cells, primarily alveolar macrophages, and disrupt the bactericidal mechanisms of these cells. The role of the polymorphonuclear leukocyte is less clearly understood. Many members of the genus produce a number of toxins which may be responsible for some of the pulmonary and extrapulmonary manifestations of disease. PMID- 3328892 TI - Clinical and laboratory aspects of Legionnaire's disease. AB - Legionnaires' disease is an illness with protean manifestations that are due to infection with Legionella pneumophila. It occurs both in epidemic and sporadic form and usually presents as an atypical pneumonia. Relative bradycardia, abnormal liver function test results, and a patient presenting with an atypical pneumonia should alert the clinician to the possibility of Legionella. The presence of systemic involvement, specifically neurological, gastrointestinal, and renal abnormalities, should further suggest the diagnosis. Patients may demonstrate multiple extrapulmonary manifestations of legionnaires' disease, sometimes without pneumonia. Several methods are available to aid the clinician in making the diagnosis of legionnaires' disease, and the use of all tests will increase the overall sensitivity. PMID- 3328893 TI - The laboratory diagnosis of Legionnaires' disease. AB - Legionnaires' disease can be diagnosed by culture, by direct detection of the bacterium or its products by using immunologic means, with a DNA probe, and by serologic means. Culture diagnosis is the most specific and sensitive test. Legionellae can be isolated from sputum samples by using selective techniques. Antibody detection is more suited for epidemiologic purposes than for use in individual cases. Immunofluorescent microscopy is a useful and rapid means of diagnosis. Alternative rapid and specific tests are urinary antigen detection and the use of a DNA probe. Culture must always be performed for optimal sensitivity and for epidemiologic purposes. PMID- 3328895 TI - Nosocomial Legionnaires' disease. AB - Members of the family Legionellaceae have emerged as important nosocomial pathogens. Bronchopneumonia is the typical illness and mimics other nosocomial pneumonias. On rare occasion, surgical wound infections may be due to legionellae. Legionella pneumophila is the species causing most human illness, but other species may predominate in individual institutions. Pneumonia is acquired by inhalation of environmental aerosols from water sources contaminated by Legionella sp. In the hospital setting contaminated water sources include potable water, heat-exchange systems, and cooling towers. Water temperature control and maintenance programs may prevent colonization of water systems. Should clinical cases and water colonization occur, aggressive suppression/eradication programs--by chlorination or heat/flush--must be instituted. Surveillance of pneumonias in high-risk patient groups is essential for early detection of a nosocomial outbreak. There has been no evidence of person-to-person transmission. Familiarity with diagnostic techniques and their pitfalls will permit institution of effective antimicrobial therapy. PMID- 3328894 TI - The radiologic manifestations of Legionella pneumonia. AB - A number of radiologic features on chest X-ray may aid in diagnosis and management of the patient with legionella infection. The infiltrates in legionnaires' disease frequently progress despite initiation of appropriate antibiotic therapy. Pleural effusion is common and occasionally seen even in the absence of lung field infiltrates. Pleural-based infiltrates associated with pleuritic pain may mimic pulmonary embolism. Circumscribed peripheral densities are commonly seen in immunosuppressed patients. Cavitation is also a prominent feature in this patient group and may develop during clinical improvement. Radiographic severity does not correlate with clinical outcome. Resolution of infiltrates may be slow, and the tendency for delayed clearing should be considered before initiating further invasive diagnostic investigation. Infections due to Tatlockia (Legionella) micdadei and Legionella bozemanii are more commonly reported in immunocompromised hosts; the radiographic manifestations are similar to those seen in Legionella pneumophila infection in the immunosuppressed. PMID- 3328896 TI - Infections caused by the Pittsburgh pneumonia agent. AB - Of the Legionellaceae family, Pittsburgh pneumonia agent (Tatlockia micdadei, Legionella micdadei) is second only to Legionella pneumophila in causing human pneumonia. In nosocomial infection, the patients tend to be immunosuppressed. The clinical presentation is nonspecific, although in immunosuppressed hosts the presentation may mimic that of pulmonary embolus (pleuritic chest pain, nonproductive cough, pleural-based densities on chest rontgenogram). The reservoir for the organism is water, and prevention of nosocomial infections can be accomplished by disinfection of the water supply. Diagnosis is best established by isolation of the organism from respiratory secretions by using selective, dye-containing buffered charcoal-yeast extract agar. The organisms can be acid-fast when clinical specimens are stained. Erythromycin is the antibiotic of choice, although tetracyclines, trimethoprim-sulfamethoxazole, and rifampin have also proved to be efficacious. PMID- 3328897 TI - Legionella-like organisms. AB - The family Legionellaceae contains the new genus and species Legionella pneumophila; organisms that resemble L pneumophila but differ in one or more phenotypes are called legionella-like organisms and constitute a growing list of new species now numbering over two dozen, and the characterization of additional species of legionellae continues to expand. Similar to L pneumophila, some of these new species have additional serogroups within the species. These new species have varying degrees of clinical and epidemiological importance. We will review historical, laboratory, and clinical aspects of Legionella species other than L pneumophila and L micdadei. PMID- 3328898 TI - Therapeutic considerations in the treatment of Legionella infections. AB - Selection of therapy for legionella infections originated with the clinical observation after the 1976 Philadelphia outbreak that patients treated with erythromycin or tetracycline did better than those who received cephalosporins or aminoglycosides. Early in vitro antibiotic susceptibility studies suggested that rifampin and erythromycin were both active against Legionella pneumophila. However, subsequent in vitro susceptibility studies to other antibiotics have produced variable results, depending on the medium and methodology used. Antibiotic studies within polymorphonuclear leukocytes and alveolar macrophages indicate that those actively concentrated within these cells are predictive of successful therapy. These include erythromycin, rifampin, and certain quinolones. On the other hand, beta-lactam antibiotics such as penicillin, cefoxitin, and imipenem are less likely to be successful because of their lack of concentration within phagocytes. These observations have been confirmed in animal model studies where erythromycin, rifampin, and quinolones have demonstrated efficacy. The addition of rifampin to erythromycin or to doxycycline may be more effective than therapeutic results with either antibiotic alone. Although erythromycin is presently the treatment of choice for legionellosis, the addition of rifampin is recommended, particularly in immunocompromised patients. Doxycycline has served as an appropriate alternative agent, the newer quinolones may be useful and are deserving of carefully designed clinical trials. PMID- 3328900 TI - [Transplantation. A new heart is a new life]. PMID- 3328899 TI - Manual of culture methodology for Legionella. PMID- 3328901 TI - [Ultrasonic study of the stomach and colon]. PMID- 3328902 TI - [Attitude of community physicians and patients with hypertension toward implementation of rehabilitation measures in ambulatory clinics]. AB - Altogether 500 persons with borderline arterial hypertension and patients with essential hypertension and 58 community internists were interviewed with the help of special questionnaires as to opportunities of various rehabilitation measures in outpatient clinics. The problem of the internists' and patients' attitude towards nonmedicamentous (salt-free diet, exercise therapy and autotraining) and medicamentous (intermittent and continuous antihypertensive therapy) methods was discussed. The authors provided information on the main reasons for the rejection of patients with essential hypertension of regular treatment in a clinic. PMID- 3328903 TI - [Interleukin 1 and its role in human pathology]. PMID- 3328904 TI - [Dissolving of biliary calculi by oral solvents]. PMID- 3328905 TI - [Auriculo-electropuncture in rheumatoid arthritis (a double-blind study)]. AB - A study of the efficacy of auriculo-electropuncture (AEP) by a double blind method was conducted in 16 patients with rheumatoid arthritis (RA). Points on the auricle were looked for by means of an device of individual use. After that during true AEP (the study group of 10 patients) the device was switched on to the stimulation mode, during false AEP (the control group of 6 patients) it was switched off. Each patient was given 10 procedures except one patient of the study group in whom treatment had to be discontinued after the 3rd procedure because of the development of phlebitis of the left crural veins. Subjective assessment showed improvement in all the patients of the study group (considerable improvement in 2 patients), in the control group improvement was noted in one patient only, no effect--in 3 patients, deterioration--in 2 patients; objective assessment showed improvement in 6 (considerable improvement in one patient) and in one patient, no effect--in 2 and 2, deterioration in one and 3, respectively. In the study group a positive time course of all 8 indices characterizing a degree of pain and inflammatory activity was noted (it was statistically significant for 7 of them), in the control group a positive time course of 3 indices was noted, 5 indices grew worse. A statistically significant decrease in the initially elevated level of blood alpha (2)-globulin was noted against a background of true AEP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3328906 TI - [Comparative effectiveness of chrysanol and auranofin in rheumatoid arthritis]. AB - A randomized study of 46 patients with classic and definite rheumatoid arthritis on chrysotherapy (25 patients--auranofin orally and 21--allochrysine intramuscularly) showed a therapeutic effect of both drugs. Allochrysine turned out more effective, it was not abandoned in any patients as a result of its inefficacy. However as compared to allochrysine auranofin was slightly better tolerated. PMID- 3328907 TI - [Hepatopancreatic syndrome in chronic alcoholism]. AB - The results of puncture biopsy of the liver, ultrasonic and angiographic investigation of the liver and pancreas in 114 patients with chronic alcoholism revealed an increment of changes in these organs in parallel with an increase in the duration of chronic alcoholic intoxication. A simultaneous study of immunoreactive insulin (IRI) and C-peptide showed that an increase in the IRI basal level in the patients suffering from alcoholism up to 10 yrs was determined mainly by an increase in the activity of beta-cells. In a long period of alcoholism an increase in the IRI basal level resulted from a decrease in the rate of insulin degradation in the liver as assessed by a lower level of C peptide. In liver cirrhosis a noticeable decrease in pancreatic incretory function was combined with noticeable disturbance of insulin degradation in the liver. The above investigations showed that there were morphological, functional and clinical signs of the "hepatopancreatic syndrome" in chronic alcoholism. PMID- 3328908 TI - Theoretical basis of antilipolytic and phospholipase inhibitory therapy in acute myocardial ischaemia. PMID- 3328909 TI - Hungarian physicians abroad in the past centuries. PMID- 3328910 TI - Pharmacotherapy of neurotic patients. PMID- 3328911 TI - Present-day situation of the "aspirin dilemma". PMID- 3328912 TI - Doxycycline in clinical practice. PMID- 3328913 TI - Reference list of biomedical and clinical publications, Uppsala 1986. PMID- 3328914 TI - American Ophthalmological Society. Directory. PMID- 3328915 TI - Solar retinopathy: a photobiological and geophysical analysis. PMID- 3328916 TI - A common pathway for developmental glaucomas. AB - In a clinicopathologic study of ten patients, utilizing a modified trabeculectomy technique for acquisition of histologic specimens, a high insertion of the iris was observed in four types of developmental glaucoma. A survey of the literature revealed additional developmental disorders with this abnormality of the anterior chamber angle. The common defect is believed to arise from a developmental arrest during the third trimester of gestation of tissues derived from cranial neural crest cells. The mechanism by which this developmental defect leads to aqueous outflow obstruction may, in some cases, be a paradoxical collapse of the trabecular meshwork and Schlemm's canal in response to contraction of the ciliary musculature, while other patients may have additional developmental abnormalities in the aqueous outflow system as the possible mechanism of glaucoma. PMID- 3328918 TI - Penetrating keratoplasty for the treatment of pseudophakic corneal edema associated with posterior chamber lens implantation. PMID- 3328917 TI - Assessment of success and complications of triple procedure surgery. PMID- 3328920 TI - Computerized ultrasonic biometry and imaging of intraocular tumors for the monitoring of therapy. PMID- 3328919 TI - The efficacy of conjunctival biopsy as a screening technique in lysosomal storage disorders. PMID- 3328923 TI - [Mechanism of adenovirus transcription]. PMID- 3328922 TI - [Pathogenesis and immunology of lactic dehydrogenase virus (LDV)]. PMID- 3328924 TI - [Results of molecular genetic studies of cultured and pathogenic strains of Treponema pallidum]. PMID- 3328921 TI - Characterization of the choroidal mast cell. AB - The experimental studies performed on nonpigmented rat choroids and the review of the important literature covered in this thesis seem to justify the following statements: 1. Mast cells are present in the choroid in significant numbers. 2. Mast cell numbers vary considerably from one individual to another and from one location in the choroid to another. 3. The major concentration of mast cells in the uvea is in the posterior choroid. 4. The mast cells of the choroid have a preferential location along arterial vessels. 5. Choroidal mast cell population density apparently decreases with senescence. 6. Mast cell products are present in sufficient quantity to exert substantial effects on physiologic, immunologic, and inflammatory responses in the choroid. 7. Choroidal mast cell products are released with appropriate stimulation and share some properties with the connective-tissue mast cell. 8. Choroidal mast cell demonstrate enough differences to suggest that a local differentiation may be present and may represent a locally controlled modulating effect for choroidal physiologic, immunologic, and inflammatory reactions. PMID- 3328926 TI - Development of mathematical models for an in vitro-phagocytosis test system. AB - Phagocytosis tests have been carried out by many authors using different methods under different conditions. The results have been interpreted in different ways, as well sometimes with conflicting notations. In order to get to a more systematic data analysis and to separate intrinsic from methodic influences, the possibility to apply mathematical models to a phagocytosis test has been studied. In agreement with previous experiences that phagocytosis can well be represented by a mathematical treatment as Michaelis-Menten-type enzyme kinetics concerning its initial rate and by an exponential function under in vivo conditions, in vitro-phagocytosis was phenomenologically described as an analogon of an irreversible bimolecular chemical reaction. In this way, rate and capacity of phagocytosis may be quantified separately. On the basis of systematic deviations of the data from this model, modifications have been developed which could be connected with pertinent observations. The design of further experiments from preliminary results on the basis of our models is discussed. PMID- 3328925 TI - [Viral papillomas of man]. PMID- 3328927 TI - Active immunization of NMRI mice against Serratia marcescens. II. K-antigen extracts. AB - The minimal active immunogenic doses (intraperitoneal administration) of crude K antigen extracts of Serratia marcescens for NMRI mice were 80 ng. Following ultracentrifugation (300,000 x g, 16 h), supernatant fluids of three K-antigen extracts were free of contaminating DNA, RNA, and 2-keto-3-deoxy-D-manno-octonic acid (KDO), and the contents of Limulus amoebocyte lysate-reactive lipopolysaccharide (LPS) had been reduced from 100- to 1000-fold. The minimal active immunogenic doses of two ultracentrifuged K-antigen extracts were 2 and 10 micrograms, respectively. A mucoid strain of S. marcescens (SM 20-M; serotype O6/O14:H12) yielded nonmucoid (= SM 29-NM) variants that had lost most of the O6/O14 O-antigen (LPS) and all of the SM 29-M K-antigen extract reactivity (ELISA test) and which were ca. 5-fold less mouse-virulent. Crude K-antigen extracts from S. marcescens strain SM 29-M and variant SM 29-NM failed to protect NMRI mice against strain SM 29-M. PMID- 3328928 TI - [Prevention of vascular diseases of the nervous system]. AB - On the basis of the literature data and the findings of their own studies the authors consider methodological aspects of the prevention of vascular diseases of the nervous system. Epidemiological, prenosological, systemic, individualized and rehabilitative approaches to the creation of the system for the prevention of vascular diseases of the nervous system have been determined. PMID- 3328930 TI - [Dynamics of the recovery of motor functions after the stereotaxic removal of intracerebral hematomas (clinical computed tomographic study)]. AB - The recovery of impaired motor functions in patients with intracerebral haemorrhages depends on many factors. It has been proved that surgical removal of intracerebral hematomas improves the survival rate. Yet, the results of recovery primarily depend on the type of surgery. A new method of stereotaxic removal of intracerebral hematomas has a number of advantages over the open method, primarily low traumatism. The prognosis of the recovery of motor ability is determined by not only the type of surgery but by a number of other factors as well, namely, the volume and localization of the hematoma, the degree of deformation of the brain stem and the timing of surgical intervention. The results of clinical employment of the new method in 51 patients should be considered encouraging while the operation of stereotaxic removal of intracerebral hematomas appears rather promising. PMID- 3328929 TI - [Double ultrasonic scanning in the diagnosis of occlusive lesions of the brachiocephalic arteries in patients with atherosclerotic circulatory encephalopathy]. AB - In a series of 84 patients with various stages of atherosclerotic circulatory encephalopathy (ADE) the authors studied the possibility of detecting by ultrasound double scanning (UDS) of occlusive lesions of the brachiocephalic arteries and compared the results with the findings provided by cerebral angiography (AG). In a study of 35 healthy subjects normal parameters of the spectrograms of the extracranial arteries were established. In 84 patients with ADE, ultrasound double scanning revealed stenoses and occlusions of the brachiocephalic arteries in 47 cases. They were confirmed by AG and were classified into five categories. Comparison of the data demonstrated that the diagnostic reliability of UDS versus AG was 95.9%. UDS makes it possible to diagnose accurately occlusive lesions of the brachiocephalic arteries in patients with ADE and to determine indications for AG and thus may be used for screening purposes. PMID- 3328931 TI - [Informational value of the premorbid psychosocial characteristics of patients with schizophrenia for the prognosis of results of rehabilitative therapy in the clinic]. AB - The authors have compared standardized case reports contained in the data bank of "Rehabilitation Automatic Information System" of two groups of schizophrenic patients who received a course of rehabilitation therapy. The first group comprised 173 patients with A and B remissions; the second, 155 patients with C, D, O remissions. A total of 343 signs characterizing the premorbid condition of the patient have been analyzed. Eighty of them have been found to differentiate the two groups on a statistically significant level. Fifty of the most prognostically informative indicators have been used for developing on the basis of image recognition algorithms of the principal rules for the individual prognosis of the type of remission. PMID- 3328932 TI - [Torpid schizophrenia--myth or clinical reality?]. PMID- 3328933 TI - [Histologic-morphometric studies to determine the cervical marginal fit of single and pontic crowns]. PMID- 3328934 TI - [The management of missing teeth in children and adolescents (an interdisciplinary problem)]. PMID- 3328935 TI - [Oral hygiene and esthetics in the management of edentulousness]. PMID- 3328936 TI - [Orthodontics in the scope of unified oral medicine]. PMID- 3328937 TI - [Oro-maxillofacial surgery in cooperation with prosthodontics and orthodontics]. PMID- 3328938 TI - [Forced maxillary expansion. 1: Patients without malformations]. PMID- 3328939 TI - [Forced maxillary expansion. 2: Patients with cleft lip, jaw and palate]. PMID- 3328940 TI - [Dimensional characteristics in various impression methods with viscoelastic materials for inlays, crowns and bridges]. PMID- 3328941 TI - [Static latent bone cavities of the mandible]. PMID- 3328943 TI - Pyruvate kinase deficiency. PMID- 3328942 TI - [Do graphite markings on etched enamel affect the adhesion of bonded brackets?]. PMID- 3328944 TI - Red cell metabolism and hemolysis. PMID- 3328945 TI - Hematological cytochemistry: current status. PMID- 3328947 TI - Human granulocyte colony-stimulating factor: its biological actions and clinical implication. PMID- 3328946 TI - Gene structure of colony-stimulating factors. PMID- 3328948 TI - Role and mode of action of non-MHC genes that determine F1 hybrid resistance to parental lymphocyte-induced GvHR-associated immunosuppression. PMID- 3328949 TI - Significance of graft-versus-host disease in allogeneic bone marrow transplantation. PMID- 3328950 TI - Immunological approaches to the study of the mechanism of hemostasis and thrombosis: applications of monoclonal antibodies against factor IX; a review. PMID- 3328951 TI - Parathyroid hormone: a uremic toxin. PMID- 3328952 TI - Intellectual impairment in chronic renal failure. PMID- 3328953 TI - Uremic dysmetabolism and its effect on immunocompetent and erythroid cell function. PMID- 3328954 TI - Kinetics of solute removal in hemodialysis. PMID- 3328955 TI - Paired filtration-dialysis (PFD): a separate convective-diffusive system for extracorporeal blood purification in uraemic patients. PMID- 3328956 TI - The Abiko factor. PMID- 3328957 TI - Enhanced growth of E. coli in whey from sows with agalactia syndrome. PMID- 3328958 TI - [Monitoring of ventilation under positive end expiratory pressure with measurement of transcutaneous oxygen pressure (PtcO2)]. PMID- 3328960 TI - [Cholelithiasis in childhood. Apropos of 4 cases]. AB - Authors review four patients diagnosed of cholelithiasis during between 1976 1986. They emphasize the importance of abdominal ultrasonography as the technic of first choice when cholelithiasis is suspected, due to its' harmlessness and diagnostic reliability. They recommend surgical treatment even in asymptomatic cases to avoid possible complications derived from a passive attitude. PMID- 3328959 TI - [How to recognize an allergic child]. AB - The morphological signs and functional characteristics which allow the suspicion, by clinical observation, of atopy in a child are described; they are called atopic stigmata; none of them is pathognomonic and is in conjunction of possible allergic disease when they are more valuable. We stress on the significance of the family history and personal antecedents of atopic allergy. If there is atopic disease in one or both parents or some brother or sister, then the allergy-risk in the child is very important. Indications of assess serum IgE levels, as well as their limitations, are discussed. The value of cord blood IgE is useful as a predictive parameter. Diagnostic research must be restricted to what is indicated by a complete and detailed anamnesis and physical exploration. PMID- 3328962 TI - Annals index 1984/1985. PMID- 3328961 TI - Biological correlates of spatial ability and mathematical performance. PMID- 3328963 TI - Effectiveness of single dose treatment with chloroquine of malaria in West Africa and measurement of chloroquine urinary excretion. PMID- 3328964 TI - [Topography and parameters of the intertrabecular spaces of the heart ventricles in man and laboratory animals]. AB - The heart of the man, dog, cat and rabbit have been investigated using biometry and corrosive methods. In the horizontal sections the volume of the intertrabecular spaces (IS) of the ventricles has been estimated and the "coefficient of the myocardial sponginess" has been calculated as the ratio of the cavities volume to the myocardial volume. In the corrosive casts of the ventricular cavities the deviation angles of the IS casts from the axial line along the afferent and deferent tracts have been measured. Differences in manifestation of the IS in the hearts of the mammals studied have been revealed. The IS are best pronounced in the human heart, less in the dog heart and still less in the cat and rabbit hearts. For all the hearts studied predominance of the volume of the IS in the right ventricle is specific. The deviation angle of the IS casts from the axial line along the afferent tract increases from the cardiac basis towards its apex, while the deviation angle of the IS along the deferent tract decreases from the apex towards the basis. The functional predisposition of the IS is supposed to consist in providing systolic reserves of the cardiac ventricular cavities. The results of the mathematical analysis of the changes in the cast deviation angles of the IS along the afferent and deferent tracts demonstrate their role in twisting and acceleration of the blood stream in the systolic phase and slowing down of the blood stream in the diastolic phase. PMID- 3328965 TI - [Are-related morphometric characteristics of the human pancreas]. AB - Quantitative characteristics of the parenchyma and stroma of the pancreas has been determined at the age of 3 days up to 92 years. The data obtained concretize the character and dynamics of involutive changes. To take them into consideration is necessary at estimation of various pathological processes, revealed in the pancreas. PMID- 3328966 TI - [P.F. Lesgaft and V.L. Gruber]. PMID- 3328967 TI - [P.F. Lesgaft and the Chair of Anatomy of the Military-Medical Academy]. PMID- 3328969 TI - [Outstanding scientist and enthusiastic teacher (on the 150th anniversary of birth of P. F. Lesgaft)]. PMID- 3328968 TI - [Connections between the anterior thalamic nuclei in turtles (data of the peroxidase method)]. AB - It turtles, Testudo horsfieldi (Gray) connections of anterior dorsomedial and dorsolateral thalamic nuclei have been investigated by means of horseradish peroxidase, injected ionophoretically. Retrogradely labelled neurons are predominantly revealed ipsilaterally in the cerebral structures belonging to the limbic system: in the forebrain--basal parts of the hemisphere, septum, adjoining nucleus, nuclei of the anterior and hippocampal commissures, hippocampal cortex, preoptic area; in the diencephalon--in the subthalamus (suprapeduncular nucleus), in some hypothalamic structures (para- and periventricular nuclei, posterior nucleus, lateral hypothalamic area, mamillary complex); in the brain stem- ventral tegmental area, superior nucleus of the suture. Less vast connections are with nonlimbic cerebral formations: projections to the striatum, afferents from the laminar nucleus of the acoustic torus, nuclei of the posterior commissure. Similarity and difference of the nuclei investigated in the turtles with the thalamic anterior nuclei in lizards, with the anterior and intralaminar nuclei in Mammalia are discussed. An idea is suggested on functional heterogeneity of the anterior nuclei in reptiles and on their role for ensuring limbic functions at the thalamic level. PMID- 3328970 TI - [Creative legacy of P.F. Lesgaft in anatomy]. PMID- 3328971 TI - [P.F. Lesgaft and the revolutionary movement in St. Petersburg at the end of the 19th and the beginning of the 20th centuries]. PMID- 3328972 TI - [P.F. Lesgaft--one of the founders of Russian anthropology]. PMID- 3328973 TI - [P.F. Lesgaft and the origin of Russian biomechanics]. PMID- 3328974 TI - Evaluation of replica techniques for the surface ultrastructure of rodent and human palatal mucosa. AB - Two replicating techniques currently used for scanning electron microscopy were investigated qualitatively and quantitatively. The most accurate and reliable replicating material was an epoxy resin; this was superior to copper plating as the model material, despite some dimensional inaccuracies. The selected method was then used to obtain accurate elastomeric replicas of rodent and human palatal mucosa. Salivary-duct openings, epithelial cell boundaries, desquamating cells and cell-surface micropits were identified. In some areas, coccal organisms could be seen colonizing the epithelial surface. PMID- 3328975 TI - The serological response to the phenolic glycolipid of Mycobacterium leprae in Australian and Nepali leprosy patients. AB - Antibodies to the species-specific phenolic glycolipid (PGL-1) of Mycobacterium leprae and a crude M. leprae sonicate were measured by ELISA in sera from newly diagnosed and treated leprosy patients from Sydney and Nepal. IgM anti-PGL-1 antibodies were present in 88-90% of untreated patients at the lepromatous pole of the clinical spectrum and 35-55% of those at the tuberculoid pole. In treated patients with either form of the disease, IgM anti-PGL-1 antibodies were within the normal range or minimally elevated. In contrast, high levels of IgG anti-PGL 1 antibodies were detected in both treated and untreated patients. Neither IgM nor IgG anti-PGL-1 antibodies were elevated in sera from Mantoux negative controls and only one out of 15 sera from patients with untreated tuberculosis contained significant amounts of antibody. Comparison of the data from the anti PGL-1 assay with the antibody response to a crude M. leprae sonicate revealed that the latter assay yielded more variable results and discriminated less well between lepromatous and tuberculoid subjects and between untreated patients and those on therapy. Thus the IgM anti-PGL-1 response signifies the presence of active disease, particularly in multi-bacillary cases, and has the potential to be used not only to monitor the response of these patients to therapy, but also to detect subclinical leprosy in high-risk groups such as the relatives of patients with lepromatous disease. PMID- 3328976 TI - Orbital myositis: a study of six cases. AB - Orbital myositis implies orbital inflammation confined to one or more of the extraocular muscles. Orbital computerised tomography (CT) demonstrates irregular extraocular muscle enlargement which extends anteriorly to involve the tendon (muscle insertion). Six cases of presumed orbital myositis are reported, in each of whom the diagnosis was suspected clinically and confirmed by the orbital CT scan appearances. The mean age of the patients was 33 years (range 8-45 years). All presented with painful ophthalmoplegia and the majority manifested proptosis (five cases), conjunctival congestion (five cases) and periorbital and eyelid edema (two cases). Systemic corticosteroid therapy was used in two patients initially and also in another patient who relapsed, with rapid and dramatic responses. Extraocular muscle biopsy was performed in one case, disclosing features of non-specific muscle inflammation and no evidence of vasculitis. It is considered that orbital myositis is a discrete, identifiable subgroup within the spectrum of the nonspecific idiopathic orbital inflammatory syndromes; termed previously orbital 'pseudotumours'. Although the clinical features are frequently suggestive, they are nonspecific, and non-invasive investigations such as orbital ultra-sonography and CT scanning are required for precise anatomical tissue localisation and diagnosis. The role of ocular muscle biopsy is probably limited to atypical cases, or those unresponsive to steroid therapy, particularly to exclude neoplasia. Orbital myositis may be acute, subacute or recurrent. The acute form responds well to high doses of oral corticosteroids tapered gradually, but it may recur or become chronic. The subacute form of the disease responds less well. PMID- 3328977 TI - Non-Hodgkin's lymphoma as a cause of hypoadrenalism. AB - Non-Hodgkin's lymphoma which presents as adrenocortical insufficiency is rare, however, it should be a well-recognised entity because, in addition to specific chemotherapy or radiotherapy, it needs hormonal replacement. We report a patient with diffuse histiocytic lymphoma, who had remission for seven years and relapsed with Addisonian crisis. PMID- 3328979 TI - A study of real-time ultrasonography for predicting ovine foetal growth under field conditions. PMID- 3328978 TI - Chlamydial disease in koalas. PMID- 3328981 TI - Repeated sequence elements in the high molecular weight basic nuclear proteins from the winter flounder. AB - In maturing sperm of the winter flounder, histones are not replaced by protamines but instead joined by a group of high molecular weight basic nuclear proteins. Despite their large size and number of components, these proteins were reduced to a relatively simple set of peptides by a "limit" digestion with endoprotease Lys C. Nine of these peptides, that together account for half of the mass of the digest, were purified by two rounds of chromatography on a C18 reverse-phase high pressure liquid chromatographic column and analysed by sequential Edman degradation. Their sequences can be divided into two homology groups. Seven of the peptides contain all or part of a dodecapeptide consensus sequence, NH2-Ser Pro-Met-Arg-Ser-Arg-Ser-Pro-Ser-Arg-Ser-Lys-COOH, which appears to be tandemly repeated. This dodecapeptide contains a previously recognized consensus phosphorylation sequence, NH2-Arg-Ser-Arg-Ser-Pro-COOH, in which both serines are phosphorylated during the early stages of spermiogenesis. The other homology group has the sequence NH2-Arg-Arg-Val-X-X-Pro-Lys-COOH, where X-X is either Gln Thr or Pro-Ser. The dodecapeptide and heptapeptide sequences form at least 35 and 11%, respectively, of the high molecular weight basic nuclear proteins and are, therefore, repeated many times over in these proteins. A search for identical or homologous sequences within the Protein Sequence Database indicated that they are unique. The closest matches were to protamines and some viral DNA-binding proteins. PMID- 3328982 TI - The relation between stroke volume and aortic pressure at different levels of positive end expiratory pressure. PMID- 3328980 TI - Characterization of UMP synthase in dairy cattle heterozygous for a lethal recessive trait. AB - UMP synthase was characterized biochemically in dairy cattle heterozygous for a deficiency of this enzyme. Both activities comprising this bifunctional enzyme are decreased, with OMP decarboxylase more affected than orotate phosphoribosyltransferase. Immunotitration of UMP synthase activity revealed the presence of the protein product of the mutant allele in the heterozygous animals. UMP synthases from normal and deficient cattle were not distinguished from one another by kinetic constants, responses to inhibitors, pH profiles, or thermal lability. It was concluded that the 50% reduction in enzyme activity in heterozygous cattle is the result of the presence of only half the normal level of catalytically active UMP synthase. PMID- 3328983 TI - A change of hats: my experiences in the Queen Alexandra's Royal Army Corps (QUARANC). PMID- 3328984 TI - [p-Nitroanilides of amino acids and peptides and fluorescence peptide with inner fluorescence quenching as substrates for cathepsins H, B, D and high molecular weight aspartic peptidase in the brain]. AB - p-Nitroanilides of amino acids and peptides were used to study the specificity of cathepsins H and B from human and bovine brain, respectively. The specific activity of cathepsin H decreased in the following order: Arg-pNa greater than or equal to Leu-pNa greater than Ala-pNa greater than or equal to Phe-pNa greater than Pro-pNa greater than Glu-pNa; Arg-pNa was split by the enzyme 12 times as fast as Bz-Arg-pNa. Among other oligopeptide p-nitroanilides tested (Ala-Ala, Ala Leu, Ala-Ala-Ala, Ala-Ala-Leu, Gly-Gly-Leu, Gly-Gly-Phe, Gly-Leu-Phe, pGlu-Phe Leu, pGlu-Phe-Ala, pGlu-Phe), PGlu-Phe-Leu and pGlu-Phe-Ala appeared to be the best substrates for cathepsin B; Km for hydrolysis were 0.1 mM and 0.165 mM, respectively, kcat were 5.1 and 8.3 s-1, respectively. A comparative study of substrate specificity of cathepsin D and high molecular weight aspartic peptidase with the use of fluorescent substrate with inner fluorescence quenching, Abz-Ala Ala-Phe-Phe-pNa, revealed that both peptidases hydrolyzed the single bond between two phenylalanine residues, resulting in the increase of fluorescence (4.5-5 fold) of anthraniloyl tripeptide. The Km values for the substrate hydrolysis by cathepsin D and high molecular weight aspartic peptidase were 6.2 microM and 11.2 microM; kcat were 7.2 s-1 and 1.3 s-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3328987 TI - Modified hemoglobin as red blood cell substitutes. PMID- 3328986 TI - The Stockholm trial on adjuvant tamoxifen in early breast cancer. Correlation between estrogen receptor level and treatment effect. AB - The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P less than 0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P less than 0.01) and deaths by 7% (P greater than 0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor. PMID- 3328985 TI - Endocrine therapy of human breast cancer grown in nude mice. AB - Although there have been extensive studies of rodent breast tumor models, and of human breast cancer cell lines in culture, there is still need for a human tumor model which can be manipulated experimentally but also provides a valid expression of the tumor cells in a host environment. Athymic nude mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2. endocrinology and pharmacology of hormonal agents in the nude mouse; 3. endocrine sensitivity of heterotransplanted tumors; and 4. applicability and limitations of this model for the study of human breast cancer. PMID- 3328989 TI - The fight against tuberculosis in China in the last 100 years and the present situation. PMID- 3328988 TI - Microencapsulated hepatocytes: an in vitro and in vivo study. AB - Using a modified alginate-polylysine membrane, we have successfully encapsulated rat hepatocytes with little loss of viability. Urea and albumin release from encapsulated liver cells was comparable to that from non-encapsulated cells during the first 4 days in culture. Histological studies also showed that more than 50% of the encapsulated hepatocytes remained viable 35 days after implantation in the peritoneal cavity of both normal rats and rats with galactosamine induced fulminant hepatic failure. Transplantation of microencapsulated hepatocytes provides a potential clinical treatment for liver failure. PMID- 3328990 TI - Mental health in Africa: II. The nature of mental disorder in Africa today. Some clinical observations. AB - Aspects of clinical psychiatric syndromes described in Africa which are discussed include the issue of schizophrenic disorders having a better prognosis in developing countries; controversy over this is by no means at an end. There is an increasing realisation as to the frequency of affective disorders in Africa; while somatisation is common, cherished beliefs, such as the absence of guilt, have not been confirmed by more recent research. Nor is suicide as infrequent as has been suggested. The relationship of background physiological abnormalities of cerebral functioning may be relevant to some of the clinical issues that are currently under discussion in African psychiatry. PMID- 3328992 TI - Anxiety management for persistent generalised anxiety. AB - A preliminary controlled investigation of the effectiveness of Anxiety Management as a treatment for generalised anxiety disorder (GAD) is described. Patients with a primary diagnosis of GAD, in which the current episode had lasted for at least 6 months but not more than 2 years, were included. Anxiety Management, a self help treatment including procedures for managing somatic and cognitive symptoms, and for dealing with avoidance and low self-confidence, was given either immediately or after a 12-week waiting period. The average length of treatment was 8.7 sessions. Highly significant changes in anxiety, depression, and problem ratings were shown after treatment. These changes were replicated when the waiting list group had also received treatment, and gains were maintained by both groups for 6 months. Similar degrees of improvement and maintenance of change were shown in subgroups with and without minor depressive disorder or recurrent panic attacks. PMID- 3328991 TI - Is there more dementia, depression and neurosis in New York? A comparative study of the elderly in New York and London using the computer diagnosis AGECAT. AB - A computerised diagnosis, AGECAT, is applied to data from random community samples of the elderly in New York and London in order to examine the prevalence of mental illness in the two cities, especially the result reported from the same study, using a different diagnostic procedure, that the proportion of dementia was higher in New York. The greater proportion of dementia in New York is confirmed for all AGECAT's levels of diagnostic confidence, for both sexes and at all half-decades over 65 years. Provided that this difference is upheld and genetic differences can be discounted, these findings would seem to support a contributory environmental cause for dementia. Proportions of depression as a whole are similar in both cities. Syndrome case and sub-case levels of neurotic disorder are generally higher in London. PMID- 3328993 TI - History of mental handicap in Bristol and Bath. Part II. PMID- 3328995 TI - [Toward the disappearance of the French radiology industry]. PMID- 3328994 TI - [Current state of knowledge about Listeria and listeriosis]. PMID- 3328996 TI - [Strategy for a global policy on the prevention of cardiovascular complications of atherosclerosis]. PMID- 3328997 TI - [Progressive supranuclear palsy: a model of subcortical dementias]. PMID- 3328998 TI - [Development of therapeutic strategies in infertility of the couple]. PMID- 3328999 TI - [A cohort of 3000 persons treated by crenotherapy and followed over a 3-year period by the national health control service]. PMID- 3329000 TI - [Eulogy of Andre Lambling (1899-1986)]. PMID- 3329001 TI - [Parallel or diversified therapeutic measures]. PMID- 3329002 TI - Biochemical and immunochemical analyses of detergent solubilized antigens from membrane vesicles of Aspergillus fumigatus. AB - A membrane vesicle fraction isolated from exponentially growing Aspergillus fumigatus strain Ag 507 cultures was obtained by mechanical disruption of intact Aspergillus cells under specific osmotic conditions followed by a pH fractionation technique. Electron micrographs of the membrane vesicles indicated unit membrane structures free from cell wall material. High glucose-6-phosphatase and low lactate dehydrogenase activities verified the relative purity of the membrane vesicle fraction. Allergic bronchopulmonary aspergillosis (ABPA) patient and normal human sera were incubated with the membrane vesicle fraction followed by colloidal gold tagged rabbit antiserum to human IgG or IgE. Electron micrographs indicated ABPA patient sera possessed specific IgG and IgE antibodies to membranous components. The detergent octyl-beta-D-glucopyranoside was used to extract membrane vesicle components (MC). The enzyme profile of MC compared with cell sap components (CS) showed differences in types of enzymes. Two-dimensional polyacrylamide gel electrophoretic analyses of MC and CS detected components shared as well as unique to each fraction. In crossed immunoelectrophoresis using both rabbit antisera raised to MC and ABPA patient sera, 5 peaks were detected, while analysis of CS using rabbit antisera raised to CS produced 20 major peaks. Immunoelectrophoresis and double immunodiffusion data supported the crossed immunoelectrophoretic data: MC differed from CS. Enzyme-linked immunosorbent assay indicated high specific IgG and IgE antibody levels to MC in ABPA patient sera. Crossed immuno-affinoelectrophoresis with concanavalin A partially characterized the MC, which consist of components which have glycoprotein elements (i.e., containing alpha-D-glucose or alpha-D-mannose). PMID- 3329003 TI - [Diuretics in the treatment of congestive heart failure]. PMID- 3329004 TI - [Coronary vascular and extravascular resistance]. PMID- 3329005 TI - [Myogenic mechanism and elastic factor in the regulation of coronary vascular resistance]. PMID- 3329006 TI - [Hemodynamics of stenosis of the large coronary vessels]. PMID- 3329007 TI - [Energetics and ventricular work in relation to coronary circulation]. PMID- 3329009 TI - [Digital or traditional angiography]. PMID- 3329008 TI - [X-ray computerized tomography and magnetic resonance in vascular pathology]. PMID- 3329010 TI - [Doppler of the supra-aortic and intracranial vessels]. PMID- 3329011 TI - [Doppler of the limbs]. PMID- 3329012 TI - [Model for the quantitative evaluation of the Allwood phenomenon by laser-Doppler flowmetry]. PMID- 3329013 TI - [New methods for the diagnosis of vasculopathies: reflexion light rheography and transcutaneous oximetry]. PMID- 3329014 TI - [Hemodynamic control and myocardial biopsy technic in the follow-up of patients undergoing heart transplantation. Multicenter experience in Italy]. PMID- 3329015 TI - [Measurement of cardiac enzymes and infarct size]. PMID- 3329017 TI - [2-dimensional echocardiography. I]. PMID- 3329016 TI - [Hemodynamics and angiography]. PMID- 3329018 TI - [Doppler echocardiography. II]. PMID- 3329019 TI - [Dynamic electrocardiography and electrophysiological study]. PMID- 3329020 TI - [Dopamine receptors in the cardiocirculatory system: an autoradiographic study]. PMID- 3329021 TI - [Dopaminergic receptors in the cardiovascular system: their biochemical characterization and pharmacological importance]. PMID- 3329022 TI - [Dopaminergic stimulation in cardiology: its current status and future strategies]. PMID- 3329023 TI - [Sinus node disease]. PMID- 3329024 TI - [Complex arrhythmias]. PMID- 3329025 TI - [Pre-excitation syndromes]. PMID- 3329026 TI - [Paroxysmal supraventricular tachycardias]. PMID- 3329028 TI - [Radioisotope studies]. PMID- 3329027 TI - [Paroxysmal ventricular tachycardias]. PMID- 3329029 TI - Reflexes elicitable in jaw muscles and their role during jaw function and dysfunction: a review of the literature. Part III. Reflexes in human jaw muscles during function and dysfunction of the masticatory system. PMID- 3329030 TI - Orthodontic/orthopedic therapy for craniomandibular pain dysfunction. Part A. Anterior disk displacement, review of the literature. PMID- 3329031 TI - IMPATH: microcomputer assessment of behavioral and psychosocial factors in craniomandibular disorders. PMID- 3329032 TI - The oli1 gene and flanking sequences in mitochondrial DNA of Saccharomyces cerevisiae: the complete nucleotide sequence of a 1.35 kilobase petite mitochondrial DNA genome covering the oli1 gene. AB - As part of our genetic and molecular analysis of mutants of Saccharomyces cerevisiae affected in the oli1 gene (coding for mitochondrial ATPase subunit 9) we have determined the complete nucleotide sequence of the mtDNA genome of a petite (23-3) carrying this gene. Petite 23-3 (1,355 base pairs) retains a continuous segment of the relevant wild-type (J69-1B) mtDNA genome extending 983 nucleotides upstream, and 126 nucleotides downstream, of the 231 nucleotide oli1 coding region. There is a 15-nucleotide excision sequence in petite 23-3 mtDNA which occurs as a direct repeat in the wild-type mtDNA sequence flanking the unique petite mtDNA segment (interestingly, this excision sequence in petite 23-3 carries a single base substitution relative to the parental wild-type sequence). The putative replication origin of petite 23-3 is considered to be in its single G,C rich cluster, which differs in just one nucleotide from the standard oriS sequence. The DNA sequences in the intergenic regions flanking the oli1 gene of strain J69-1B (and its derivatives) have been systematically compared to those of the corresponding regions of mtDNA in strains derived from the D273-10B parent (sequences from the laboratory of A. Tzagoloff). The nature and distribution of the sequence divergences (base substitutions, base deletions or insertions, and more extensive rearrangements) are considered in the context of functions associated with mitochondrial gene expression which are ascribed to specialized sequences in the intergenic regions of the yeast mitochondrial genome. PMID- 3329033 TI - The cellular level of yeast ribosomal protein L25 is controlled principally by rapid degradation of excess protein. AB - When the gene dosage for the primary rRNA-binding ribosomal protein L25 in yeast cells was raised about 50-fold, the level of mature L25 transcripts was found to increase almost proportionally. The plasmid-derived L25 transcripts were structurally indistinguishable from their genomic counterparts, freely entered polysomes in vivo and were fully translatable in a heterologous in vitro system. Nevertheless, pulse-labelling for periods varying from 3-20 min did not reveal a significant elevation of the intracellular level of L25-protein. When pulse-times were decreased to 10-45 s, however, we did detect a substantial overproduction of L25. We conclude that, despite the strong RNA-binding capacity of the protein, accumulation of L25 is not controlled by an autogenous (pre-)mRNA-targeted mechanism similar to that operating in bacteria, but rather by extremely rapid degradation of excess protein produced. PMID- 3329035 TI - Heat shock phenomena in Aspergillus nidulans. I. The effect of heat on mycelial protein synthesis. AB - Heat shock was found to induce characteristic changes in the pattern of protein synthesis in Aspergillus nidulans as analysed by SDS-polyacrylamide gel electrophoresis. Six to seven new bands were found to show increased incorporation to 35S-methionine at 43 degrees C compared to 37 degrees C, the standard temperature for this organism. The heat shock response of five different strains of A. nidulans was examined. This comparative study showed that these strains (haploids and diploids) show exactly the same set of heat shock proteins. PMID- 3329034 TI - Behaviour of recombinant plasmids in Aspergillus nidulans: structure and stability. AB - A pyrG- Aspergillus strain was transformed with plasmid pDJB-1, derived from pBR325 by insertion of the Neurospora crassa pyr4 gene (orotidine 5'-phosphate carboxylase), giving mitotically unstable transformants. Aspergillus DNA which acted as an "autonomously replicating sequence" (ARS) in yeast was inserted into pDJB-1 and the resulting construct, pDJB12.1, gave mitotically stable transformants when introduced into Aspergillus. Transformants obtained with pDJB 1 and pDJB12.1 gave few pyr- progeny in crosses to a pyrG+ strain. Southern hybridisation analysis of pyr+ transformants obtained with pDJB-1 revealed restriction fragments expected for integrated plasmid but transformants obtained with pDJB12-1 showed only bands derived from free plasmid. pDJB-1 and derivatives of pDJB12.1 could be recovered from transformants. These derivatives could not be explained by straightforward excision of integrated pDJB12.1 sequences but could result from recombination between plasmid molecules. Hybridisation of undigested transformant DNAs showed that the transforming DNA was present in a high molecular weight form. These results suggest: (1) pDJB12.1 derivatives and possibly pDJB-1 can replicate autonomously in Aspergillus; (2) A. nidulans DNA acting as an ARS in yeast enhances replication and/or segregation of transforming plasmids in Aspergillus; and (3) recombinant plasmids may undergo rearrangements when introduced into Aspergillus. PMID- 3329038 TI - Alpha-factor enhancement of hybrid formation by protoplast fusion in Saccharomyces cerevisiae II. AB - When Mat a cells are treated with alpha-factor prior to being protoplasted and fused, the frequency of karyogamy is higher than in unarrested controls. PMID- 3329036 TI - Analysis of mutagenic DNA repair in a thermoconditional mutant of Saccharomyces cerevisiae. IV. Influence of DNA replication and excision repair on REV2 dependent UV-mutagenesis and repair. AB - A double mutant being thermoconditionally defective in mutation induction as well as in repair of pre-lethal UV-induced DNA damage (rev2ts) and deficient in excision repair (rad3-2) was studied in temperature-shift experiments. The influence of inhibitors of DNA replication (hydroxyurea, aphidicolin) was determined. Additionally, an analysis of the dose-response pattern of mutation induction ("mutation kinetics") at several ochre alleles was carried out. It was concluded that the UV-inducible REV2 dependent mutagenic repair process is not induced in excision-deficient cells. In excision-deficient cells, REV2 dependent mutation fixation is slow and mostly post-replicative though not dependent on DNA replication. The REV2 mediated mutagenic process could be separated from the repair function. PMID- 3329037 TI - The CDC25 "Start" gene of Saccharomyces cerevisiae: sequencing of the active C terminal fragment and regional homologies with rhodopsin and cytochrome P450. AB - The CDC25 Start gene whose product appears to be required for traversing the Go phase of the cell cycle in Saccharomyces cerevisiae, has been previously cloned (J. Daniel and G. Simchen (1986), Curr Genet 10:643-646). By nucleotide sequencing of an active subclone, we found that only a region of the gene that codes for the C-terminal portion of the CDC25 protein was required for full suppression of the cdc25 mutation. The codon usage in this region indicates a poor translation of the transcript compared to genes encoding abundant proteins. The derived CDC25 protein fragment contains two regions of homology, one with the rhodopsin family, the other with the cytochrome P450 family. Strikingly, these two regions of homology are adjacent on the CDC25 protein. In view of the likely involvement of the CDC25 protein in the regulation of adenylate cyclase activity, a working hypothesis is proposed that accounts for the observed homologies. PMID- 3329039 TI - Clones from two different genomic regions complement the cdc25 start mutation of Saccharomyces cerevisiae. AB - We have cloned the CDC25 gene of Saccharomyces cerevisiae whose product is required for traversing the Go phase of the cell cycle. A preliminary physical characterization of the CDC25 gene region is presented. In addition, we show that another gene, when cloned in a high-copy number plasmid, is able to partially suppress growth thermosensitivity of a strain carrying the cdc25 mutation. We briefly discuss the possible interaction of these gene products with adenylate cyclase encoded by the CDC35 gene. PMID- 3329040 TI - Alkylation mutagenesis in Saccharomyces cerevisiae: lack of evidence for an adaptive response. AB - We have found no evidence for an adaptive response for either lethality or mutagenesis following treatment of Saccharomyces cerevisiae with N-methyl-N' nitro-N-nitrosoguanidine (MNNG). The rad6 and rad52 mutants of S. cerevisiae are highly defective in MNNG and ethyl methanesulfonate induced mutagenesis of both stationary and exponential phase cells. These and other observations indicate that the mechanisms of repair of alkylation damage and mutagenesis differ markedly between S. cerevisiae and Escherichia coli. PMID- 3329041 TI - Identification and characterization of four new GCD genes in Saccharomyces cerevisiae. AB - Mutant strains, resistant against the amino acid analogues 5-methyltryptophan, 5 fluorotryptophan and canavanine were isolated, starting with a trp2 leaky auxotrophic strain. Of 10 such strains, only four turned out to be of the "general control derepressed" (gcd) mutant type. Three other isolates were shown to be defective in the general amino acid permease system, while the remaining three strains displayed low spore viability and were not further investigated. Complementation tests amongst the four new gcd-mutant strains, including strain RH558 gcd2-1 isolated earlier, yielded five complementation groups: GCD2, GCD3, GCD4, GCD5, and GCD6. All mutant strains showed a dual phenotype, which was not separable by wild type backcrosses: "constitutive derepression" and "slow growth". Epistasis of all gcd mutations over gcn1-1, gcn2-1 and gcn3-1 was found with respect to both phenotypes, except for gcd5-1, which was lethal in these combinations. On the other hand gcn4-101 was found to be epistatic over all gcd mutations, but only with respect to the "constitutive derepression" phenotype, and not to "slow growth"; again the combination with gcd5-1 was lethal. Mutation gcd2-1 was mapped on chromosome VII, 50 cM from leu1 and 22 cM from ade6. A new model is discussed, in which GCD-genes are involved in the amino acid uptake into the vacuoles. PMID- 3329042 TI - Genetic mapping of nuclear mucidin resistance mutations in Saccharomyces cerevisiae. A new pdr locus on chromosome II. AB - In the yeast Saccharomyces cerevisiae, two nuclear pleiotropic drug resistance mutations pdr3-1 (former designation mucPR) and pdr3-2 (former designation DRI9/T7) have been selected as resistant to mucidin and as resistant to chloramphenicol plus cycloheximide, respectively. The pdr3 mutations were found not to affect the plasma membrane ATPase activity measured in a crude membrane fraction. Meiotic mapping using strains with standard genetic markers revealed that mutation pdr3-1 is centromere linked on the left arm of chromosome II at a distance of 5.9 +/- 3.3 cM from its centromere and 11.6 +/- 3.1 cM from the marker pet9. The centromere linked pdr3-2 mutation exhibited also genetic linkage to pet9 with a map distance of 9.8 +/- 3.2 cM. These results indicate that pdr3-1 and pdr3-2 are alleles of the same pleiotropic drug resistance locus PDR3 which is involved in the control of the plasma membrane permeability in yeast. PMID- 3329043 TI - Effects of T-2 toxin on induction of petite mutants and mitochondrial function in Saccharomyces cerevisiae. AB - The influence of the trichothecene mycotoxin T-2 on the mitochondria of Saccharomyces cerevisiae was studied. T-2 is a cytotoxic molecule inhibiting growth and macromolecular synthesis in S. cerevisiae. At low concentrations, T-2 toxin arrested yeast growth on glycerol medium and at higher concentrations, it arrested growth on glucose medium. The toxin was not capable itself of inducing petite mutations. Its inhibitory effect on the growth of petite strains, of both chromosomally isogenic and non-isogenic strains was less than that of grande strains. One exception to this was equally low susceptibility of psi+ SUP4-3 strain in both rho+ and rho- state. T-2 toxin was also capable of retarding the petite inducing activity of the mutagen, ethidium bromide. T-2 toxin inhibited the polymerization of P-ribo-sylaminoimidazole in an ade2 strain of S. cerevisiae. These results show that T-2 toxin is capable of interfering with the activity of the mitochondria in addition to its well studied effects on cytoplasmic protein synthesis. PMID- 3329044 TI - Segregant-defective heterokaryons of Candida albicans. AB - Heterokaryons (hets) of the asexual, pathogenic yeast Candida albicans obtained by fusing protoplasts of complementing auxotrophic strains generate large numbers of parental-type auxotrophic monokaryons by random assortment of single nuclei into blastospores, and smaller numbers of monokaryons bearing hybrid nuclei formed through either karyogamy or the transfer of genetic material from one het nucleus to another. Het populations grown at 30 degrees C or 37 degrees C contain high frequencies (approx. 5%-10%) of two kinds of stable variants peculiar specifically for segregation of parental-type monokaryons: NS variants produce inviable auxotrophic monokaryons of one or both parental classes while AT variants yield parental-type monokaryons which grow very slowly. Variant frequencies are not affected by the wild-type strain background of hets, or the auxotrophies used to force heterokaryosis. However, both kinds of variants are induced by growth at 25 degrees C or by treatments with certain chemical or physical metabolic inhibitors. Evidence is presented that variant nuclei of independent origins carry different nutritionally irreparable recessive lethal (NS) or debilitating (AT) defects acquired in the course of actual or potential internuclear transfers of genetic material within het cells. The high incidence of variants, therefore, indicates considerable intrinsic genetic instability among het nuclei. Significances of these observations for parasexual genetic analyses of C. albicans and other yeasts through protoplast fusions are considered. PMID- 3329046 TI - Transformation of psi- Saccharomyces cerevisiae to psi+ with DNA co-purified with 3 micron circles. AB - DNA enriched for supercoiled plasmids prepared from the 3 micron plasmid enriched, [psi+], [2 micron degrees] strain 6-1G-P188 and from the [2 micron+] [psi+] strain LL20 can be used to transform a psi- recipient strain to psi+. Fractionation of the former preparation by electrophoresis showed that the 3 micron plasmid band contained the transforming activity. PMID- 3329047 TI - Induction of yeast DNA ligase genes in exponential and stationary phase cultures in response to DNA damaging agents. AB - UV-irradiation of stationary phase cells of Saccharomyces cerevisiae and Schizosaccharomyces pombe leads to a 9-fold and 90-fold increase in transcript levels from the respective DNA ligase genes CDC9 and CDC17, whereas exponential cells show only 3-fold and 2-fold increases. Induction of CDC9 after MMS treatment and gamma-irradiation was also observed by using a CDC9-lacZ translational fusion and assaying for beta-galactosidase. Surprisingly, irradiation of S. cerevisiae induces only a 50% increase in DNA ligase itself, probably reflecting the extremely high in vivo stability of the enzyme. The UV induction of ligase may be part of a "fail-safe" mechanism which, together with the enzyme stability, ensures adequate supplies of this essential enzyme. PMID- 3329045 TI - Two yeast nuclear genes, CBS1 and CBS2, are required for translation of mitochondrial transcripts bearing the 5'-untranslated COB leader. AB - Mutations in one of the yeast nuclear genes CBS1 or CBS2 both prevent the excision of the maturase-coding introns bI2, bI3 and bI4 from the mitochondrial COB precursor transcript. Mutant strain MK2 (cbs1-1) has recently been reported to be primarily defective in the translation of COB transcripts, as it can be suppressed by a fusion of the COB structural gene with the 5' untranslated leader of the mitochondrial OLI1 gene (G. Rodel, A. Korte and F. Kaudewitz, Curr Genet 9: 641-648). Here I report that the effect of mutation cbs2-1, too, is suppressed by this gene rearrangement. CBS2 is the second nuclear gene identified which is involved in the translation of mitochondrial transcripts bearing the 5' untranslated COB leader. Gene specific translation control appears to be a major mode of regulation of mitochondrial gene expression in Saccharomyces cerevisiae. PMID- 3329048 TI - Trehalose and maltose metabolism in yeast transformed by a MAL4 regulatory gene cloned from a constitutive donor strain. AB - A 6.8 kb fragment of DNA containing the regulatory sequence MAL4p has been cloned from a genomic library prepared from Saccharomyces cerevisiae strain 1403-7A which ferments maltose constitutively. The library was prepared by ligation of 5 20 kb Sau3AI restriction fragments of total yeast DNA into the BamH1 restriction site of shuttle vector YEp13. A restriction map of the cloned fragment indicates that it encompasses a 2.6 kb segment which closely resembles the regulatory MAL6 gene previously identified (Needleman et al. 1984). The hybrid plasmid, p(MAL4p)4, could transform maltose-nonfermenting strains which contain cryptic alpha-glucosidase and maltose permease genes (malp MALg), but could not transform strains containing a functional regulatory sequence and a defective maltase permease region (MAlp malg). A correlated absence of maltase and permease DNA from the cloned fragment was indicated by the restriction map. Although the cloned DNA fragment was derived from a constitutive strain, maltose fermentation and alpha-glucosidase formation by yeast transformed with p(MAL4p)4 was largely inducible by maltose and sensitive to catabolite repression. Moreover, the active trehalose accumulation pattern (TAC(+) phenotype) linked to the complete MAL4 locus in strain 1403-7A and other constitutive MAL strains (Oliveira et al. 1981b) was not found in p(MAL4p)4 transformants. It may be concluded that constitutivity of maltose fermentation and the associated active trehalose accumulation are not merely consequences of a cis-dominant mutation causing constitutive formation of the MALp regulatory product. Moreover, constitutivity may not be caused solely by a mutation within the structural region of the MALp gene. PMID- 3329049 TI - DNA repair genes of Saccharomyces cerevisiae: complementing rad4 and rev2 mutations by plasmids which cannot be propagated in Escherichia coli. AB - The RAD4 gene of yeast required for the incision step of DNA excision repair and the REV2 (= RAD5) gene involved in mutagenic DNA repair could not be isolated from genomic libraries propagated in E. coli regardless of copy number of the shuttle vector in yeast. Transformants with plasmids conferring UV resistance to a rad4-4 or a rev2-1 mutant were only recovered if yeast was transformed directly without previous amplification of the gene bank in E. coli. DNA preparations from these yeast clones yielded no transformants in E. coli but retransformation of yeast was possible. This lead to the isolation of a defective derivative of the rad4 complementing plasmid. The modified plasmid was now capable of transforming E. coli but still interfered significantly with its growth. PMID- 3329050 TI - Isolation and genetical and biochemical characterization of mutants resistant to the alkaloid lycorine. AB - Mutants resistant to 200 micrograms/ml of the alkaloid lycorine (LYCR) in non fermentable substrate were isolated after nitrosoguanidine mutagenesis. Tetrad analysis and growth of heterozygous (LYCR/lycS) diploids from two different mutants revealed that a single nuclear and dominant mutation is responsible for the resistant phenotype. In the wild type total protein synthesis is only slightly inhibited, whereas DNA and RNA synthesis is lowered to about 30% of the control. In the lycorine resistant mutants all macromolecular syntheses are unaffected by the drug. PMID- 3329052 TI - Induced cellular resistance to ultraviolet light in Saccharomyces cerevisiae is not accompanied by increased repair of plasmid DNA. AB - Many reports show that resistance of Saccharomyces cerevisiae to a large UV dose can be enhanced by pre-induction with a smaller one given some hours before. This work tests if such increased cell survival is associated with increased DNA repair on UV damaged plasmid transformed into yeast. There was no change in transformation efficiency of UV-damaged plasmid DNA under conditions where RAD cell survival increased 5-fold, and where rad1-1 and rad6-1 survival increased 2 fold. It is concluded that DNA repair activity involving the RAD6 and RAD3 pathways is either not inducible or is unable to work on plasmid DNA. It is suggested that the enhancement of cellular survival detected may be based on changes in cell-cycle behaviour which permit cells generally proficient in repair a greater chance to recover. PMID- 3329051 TI - A mitochondrial frameshift-suppressor (+1) [corrected] of the yeast S. cerevisiae maps in the mitochondrial 15S rRNA locus. AB - The first case of a +1 "extrageneic" frameshift suppressor (MF1), mapping in the yeast mitochondrial 15S rRNA gene is reported. The suppressor was identified by genetic analyses in a leaky mitochondrial oxil frameshift mutant and the respective wild-type strain 777-3A of the yeast S. cerevisiae. This is in accordance with the finding that all mitochondrial frameshift mutants isolated from this strain tend to be leaky to a variable degree. MF1 does not suppress known nonsense mutations created by a direct basepair exchange in strain 777-3A. These mutants exhibit a non-leaky phenotype (Weiss-Brummer et al. 1984). PMID- 3329053 TI - Nuclearly-encoded CBP1 interacts with the 5' end of mitochondrial cytochrome b pre-mRNA. AB - CBP1 is a nuclearly-encoded protein that is imported into mitochondria and confers stability on the mRNA for cytochrome b. Previous work has shown that CBP1 interacts with the cytochrome b transcript upstream of the coding sequence; a region encompassing some 1,100 nucleotides. The work presented here narrows the site of action of CBP1 to the distal third of this upstream sequence through analysis of mRNA produced from a novel recombinant gene containing segments of the gene for cytochrome b, cob, and the ATP synthase subunit 9 gene, olil. In a wild-type CBP1 strain, the cob-olil-cob gene produces stable, mature mRNA that is translated and contributes a portion of the cytochrome b necessary for optimal growth on non-fermentable medium. PMID- 3329054 TI - Meiotic instability of tandemly iterated plasmid sequences in the yeast chromosome. AB - The stability of tandemly arrayed plasmid sequences in the yeast genome has been studied. Haploid strains carrying 75 copies of a 25 kb plasmid repeat did not undergo significant loss of copy number during mitosis. Diploids in which only one chromosome contained the multiple iterated sequences displayed a similarly low level of mitotic instability. In contrast, 60-90% of the meiotic diploid progeny showed significant decreases in the number of iterated sequences. Segregation for the integrated sequences was generally 2:2, indicating that interchromosomal recombination was not the cause of meiotic instability. Meiotic progeny from diploids in which both chromosomes contained multiple integrated sequences also showed the same high rate of loss of iterated sequences. These results suggest that the meiotic instability is a result of intrachromosomal recombination, a process which is enhanced during meiosis. PMID- 3329057 TI - A simple method of studying cardiac conducting tissues. PMID- 3329055 TI - Induction and isolation of mutants in fungi at low mutagen doses. AB - Since the yield of mutants per surviving cell increases in general with increasing dose of mutagen, it has often been concluded in the literature that it is the most efficient to apply high mutagen doses so that most spores are killed. As high doses of mutagen produce chromosome rearrangements and unnoticed mutations which disturb the genetic background, the relationship between mutant frequency and survival was analyzed with Aspergillus nidulans as a model. It is shown that for different types of mutants the highest mutant yield is obtained at low mutagen doses (20-50% survival). Mutant frequency increases with increasing dose of mutagen but levels off and even decreases at higher dosages. There is no simple linear relationship between mutant frequency and the logarithm of the mutagen dose or the logarithm of the surviving fraction. If appropriate enrichment procedures are also available auxotrophic mutants can best be isolated at low doses of mutagen. Taking into account the disturbance of the genetic background, mutation induction should be done preferentially at a survival level of at least 70%. PMID- 3329058 TI - [Current status of research on chronic atrophic gastritis in traditional Chinese medicine and Western medicine]. PMID- 3329056 TI - The isolation of specific genes from the basidiomycete Schizophyllum commune. AB - We have developed a routine way to isolate genes directly from the basidiomycete fungus, Schizophyllum commune. Plasmid DNA from a genomic gene library was used to isolate five specific genes by complementation of Schizophyllum mutations via transformation. The mutant strains were deficient in the ability to synthesize either adenine (ade2 and ade5), uracil (ura1, encoding orotidine-5'-phosphate decarboxylase; OMPdecase), tryptophan (trp1, encoding indole-3-glycerol phosphate synthetase; IGPS) or para aminobenzoic acid (pab1). In each case, Southern analysis revealed that transformation to prototrophy was concomitant with the integration of vector sequence into the genome of the S. commune mutant. Total DNA from transformants was restricted, religated, and used to transform E. coli. Ampicillin resistant plasmids were recovered from E. coli and tested for their ability to transform the corresponding mutant of S. commune. Plasmids complementing the ade2, ade5, pab1, trp1, and ura1 mutations were recovered. PMID- 3329059 TI - [Acute intestinal invagination in infants and children, critical evaluation of the diagnostic and therapeutic strategy. Apropos of a series of 163 cases]. AB - This study concerns a homogenous series of 163 cases of intussusceptions in children, seen in the Visceral Pediatric Surgical Unit of Montpellier from 1974 to 1985. The authors differentiate and compare two periods with regard to the year 1980: the first one (P1 = 64 cases) during which, surgery was always the rule;the current one (P2 = 99 cases) where non operative treatment is the modality of choice under precise conditions. Synthetic analysis and comparison of the different therapeutic groups which have been distinguished in every period lead to the following data. 14% of intussusceptions are directly operated whatever the period or the modality of management probably because this group represents the absolute contra-indications of a barium enema--It concerns children with a long duration of the disease, obstructive or peritonitis signs and late diagnosis--Laparotomy is mandatory and finds a high percentage of leading points and ileo-ileal forms. Intestinal resection was necessary in 59.5% of cases. Because of this and a poor general condition, morbidity was high and Hospital stay was long. 56.4% of intussusceptions are operated after failure of barium enema reduction. This hydrostatic irreducibility is probably explained by the prevalence of ileo-colic forms (53.3%) in this group. A shorter duration of the disease (less than 2 days in 43.1%) and a strong majority of idiopathic intussusception (90.5%) are surely responsible of a high percentage (80%) of successful manual reduction without the need of a resection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3329061 TI - [Pancreas divisum: anatomic variation with or without true disease? Description of a case and discussion]. PMID- 3329060 TI - [Ureteral triplication]. AB - Two cases of ureteral triplication are reported, on in a child of 4 years the other in a 2-week-old baby. In both cases the triplication was associated with one or two ureteroceles. A literature review is used as a basis for describing the characteristics of this rare malformation. PMID- 3329063 TI - Arterial embolization of the spleen. PMID- 3329062 TI - [Integrated approach to abdominal abscesses by diagnostic and interventional imaging]. PMID- 3329064 TI - [Immunopathological mechanisms in the origin of human glomerular nephropathies]. PMID- 3329065 TI - Detection of periodontal disease: parameters to assess periodontal disease activity. PMID- 3329066 TI - [A preliminary study on the infectivity of different geographic strains of Plasmodium vivax to Anopheles sinensis]. PMID- 3329068 TI - [Studies on control measures of vivax malaria in Juye County, Shandong Province]. PMID- 3329069 TI - [Detection of serum antibodies in bancroftian filariasis patients with antigens from different developmental stages of Brugia malayi]. PMID- 3329070 TI - [Combined use of pyronaridine, sulfadoxine and primaquine in areas with chloroquine-resistant falciparum malaria]. PMID- 3329067 TI - [Susceptibility of Plasmodium falciparum to chloroquine, piperaquine, amodiaquine, mefloquine and quinine with in vitro microtechnique in Hainan Island]. PMID- 3329071 TI - A 20-year retrospective study of the use of contact lenses in keratoconus. PMID- 3329072 TI - Paecilomyces lilacinus keratitis: two case reports in extended wear contact lens wearers. PMID- 3329074 TI - Facilitation of drug entry into brain by osmotic opening of the blood-brain barrier. AB - 1. After osmotic opening, the blood-brain barrier (BBB) has been shown to reclose more rapidly to large than to small neutral, water-soluble molecules. Quantitative analysis of these data supports the creation of interendothelial pores with radii of about 200 A through which such molecules pass by both restricted diffusion and bulk flow (with solute drag) from blood to brain. 2. The major reduction in BBB permeability from 6 to 35 min following osmotic opening seems to be due to a reduction in bulk flow by a factor of about 10, rather than marked decreases in pore densities or effective pore size. On this basis, quantitative predictions of brain uptake of neutral, water soluble substances are made for various times after osmotic opening of the BBB, as a function of molecular size. 3. Implications of these results are discussed for enhancement of uptake of drugs, including enzymes and certain anti-cancer agents, by the brain. 4. The idea of a 'therapeutic window' as the period of time, following reversible osmotic opening, during which the permeability of the BBB is enhanced significantly for a particular compound, is introduced. Since the BBB is normally highly impermeable to plasma proteins, the effect of BBB opening on the uptake of highly protein-bound drugs is discussed briefly. 5. The effect of molecular charge on the passage of molecules through interendothelial pores into the brain is also discussed. PMID- 3329075 TI - [Report on an autopsy of a cancer patient with Carmofur (HCFU) leukoencephalopathy]. PMID- 3329073 TI - Amitriptyline action on sympathetic neuronal function in depressed women. AB - 1. Noradrenaline plasma levels and cardiovascular function modifications with orthostatic challenge during therapy were studied in 59 female depressed inpatients treated with 100 mg amitriptyline daily by intramuscular route for 4 weeks. 2. Therapy induced an increase in pulse rate in supine and upright positions, a decrease of noradrenaline levels and modified standing systolic and (partially) diastolic blood pressure, particularly in elderly subjects. 3. No correlation between neurotransmitter or functional changes and drug plasma levels was noted. 4. The supposed lower noradrenergic output together with blood pressure drop in both positions suggests a reduced sympathetic tone. PMID- 3329077 TI - Sensitive immunoenzymatic assay for urinary immunoglobulin subclasses of different pH: its significance in diabetic patients. AB - In search of a marker for monitoring the progression of diabetic nephropathy from the stage of charge- to that of size-selectivity loss, attention has been focused on the evaluation of immunoglobulin G (IgG) subclasses in the urine. We have developed a new sensitive enzyme immunoassay for the quantitation of urinary IgG1 and IgG4. Mouse monoclonal antibodies specific for each subclass were bound to microtitre wells precoated with rabbit anti-mouse immunoglobulin antibody. IgG1 and IgG4 of standard preparations (or of samples to be tested) were revealed using peroxidase-conjugated rabbit anti-human IgG. The procedure was carried out at 4 degrees C. This method can detect about 2 ng/ml of IgG4 and 20 ng/ml of IgG1. The monoclonal antibodies used were shown to be highly subclass-specific. IgG1 and IgG4 have a similar molecular weight but a different pH (about 9 and 4.6 respectively); a change in their ratio in the urine of diabetic patients may indicate a progressive deterioration of kidney function at the stage of incipient diabetic nephropathy. PMID- 3329076 TI - Electron microscopical investigations on lymphocyte cytotoxicity against beta cells in recent onset IDDM. AB - The effect of lymphocytes from patients with newly diagnosed insulin dependent diabetes on isolated rat or human islets during a 20 h in vitro incubation was investigated by morphological and biochemical methods. All stages of target cell reaction of lymphocytes against beta-cells were observed. Cytoplasmic projections towards and contacts with beta-cells, circumscribed lysis of the outer cell membrane at the contact side and complete lysis of beta-cells were seen. Such findings could not be registered with alpha- or other non beta-cells and in control experiments using lymphocytes from healthy persons. In some cases the lymphocytes were phenotyped using monoclonal antibodies by the indirect immuno gold technique. It could be demonstrated that lymphocytes in contact with necrotic beta-cells were of the CD8+ve subset. In addition the morphological investigations were supplemented by quantitative biochemical studies measuring the non-secretory insulin release ("cytotoxic" release) from islets into the culture medium and their ability to respond to a consecutive stimulation by arginin with insulin and glucagon secretion. The mean cytotoxic insulin release was 11.3 +/- 1.5 ng/islet/20 h (n = 25) in the diabetic group versus 0.56 +/- 0.15 ng/islet/20 h (n = 15) in the control subjects (alpha less than 0.001). Functional testing of the islets following incubation with lymphocytes from diabetic patients showed diminished insulin (58.6 +/- 5.1%, n = 18, alpha less than 0.001) and unchanged glucagon response (103.0 +/- 3.4%, n = 10, n.s.) when compared with untreated islets (= 100%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3329078 TI - Clinical acceptability, use-patterns and use-effectiveness of the vaginal contraceptive sponge and Neo Sampoon tablets--an international multi-center randomized clinical trial. AB - This paper describes the results from a randomized clinical trial comparing the Collatex vaginal contraceptive sponge (a predecessor of the Today sponge) and Neo Sampoon foaming vaginal contraceptive tablets; the trial was conducted from 1979 to 1983 in four centers located in three countries (two in Yugoslavia and one each in Taiwan and Bangladesh). The sponge was associated with more insertion and retention problems than the tablet, especially in the two Asian centers. More Neo Sampoon users complained of a burning or stinging sensation. This complaint, however, seemed to be well-tolerated and was not a frequent reason for irregular use and/or discontinuation of use of the tablets. Clinically significant medical complications were rarely reported for either method. Sponge users were more likely to report irregular use than tablet users, primarily due to inconvenience of use. Rates of discontinuation at six months of use were also consistently higher among sponge users than Neo Sampoon users in the four centers. Life-table pregnancy rates at 12 months of use ranged from 3.8 to 18.2 per 100 sponge users and 6.2 to 29.9 per 100 Neo Sampoon users, based on data from the two Yugoslavian centers and the Taiwan center (data from the Bangladesh center were excluded from analysis of pregnancy rates). Practical implications of these findings are discussed. PMID- 3329079 TI - A comparative study of Norinyl 1/35 versus Norinyl 1/50 in Belgrade, Yugoslavia. AB - A comparative study of Norinyl 1/35 and Norinyl 1/50 was conducted at the Dom Zdravlja Stari Grad in Belgrade, Yugoslavia. The study sought to evaluate the differences in continuation rates as well as the frequency of selected side effects which might contribute to method discontinuation. The trial included 299 women who were randomly allocated to one of the two oral contraceptives. In the Norinyl 1/35 group, significantly more women (p less than .05) reported a complaint of vaginal discharge as well as an increase in the occurrence of vaginal discharge compared to the Norinyl 1/50 group. There was no significant difference in continuation rates or for particular discontinuation reasons for the Norinyl 1/35 and Norinyl 1/50 groups. No accidental pregnancies were reported during this study. Both oral contraceptives appear to be safe and effective; there appears to be no difference in the acceptability of one oral contraceptive over the other among this group of Yugoslavian women. PMID- 3329080 TI - [1917-1987: 70th anniversary of the periodical Chirurgia degli Organi di Movimento. Homage to Vittorio Putti (1880-1940)]. PMID- 3329081 TI - [Ultrasonographic study in the evaluation of acute capsulo-ligamentous lesions of the medial compartment of the knee]. PMID- 3329082 TI - [Removal of bone cement in reinterventions in arthroprosthesis of the hip]. PMID- 3329083 TI - [Experimental study on freeze-dried homogenic brephobone graft]. PMID- 3329084 TI - [Experimental study on recombined xenogeneic bone transplants in the mandible]. PMID- 3329085 TI - [Clinical application of decalcified allogeneic bones]. PMID- 3329086 TI - [Etched casting resin bonded bridge: a laboratory study of electrolytic etching of a Co-Cr alloy]. PMID- 3329087 TI - [Application of NOSIE in the study of neuroleptic treatment]. PMID- 3329088 TI - [Atherosclerotic lesions of the extracranial portion of the carotid artery system in transient cerebral ischemia patients]. PMID- 3329089 TI - [Behavior of fatty acid patterns in serum lipids in type I diabetic patients in intensive conventional insulin therapy]. AB - The relationship between an improvement of the carbohydrate metabolism due to a four-week intensified conventional insulin treatment and changes in fatty acid patterns of serum lipids was investigated in 12 insulin-dependent diabetic patients. At the commencement of the study the diabetic patients were characterized by higher relative linolic acid contents in the serum cholesterolesters and phospholipids in comparison with control subjects. The intensified insulin treatment was associated with a significant improvement of the glycaemic control, whereas the fatty acid patterns of the serum lipids remained unchanged. The results demonstrate that short-time improvement of the carbohydrate metabolism is not associated with qualitative changes of serum lipids in insulin-dependent diabetic patients. Remains to be established the long term effect of improved metabolic control on fatty acid metabolism. PMID- 3329091 TI - Changes in adrenal responsiveness and potassium balance with shifts in sodium intake. AB - Dietary sodium modulates the aldosterone response to angiotensin, but available evidence does not indicate whether there is a gradual change in adrenal responsiveness with intermediate sodium intakes or a sharp shift from a low to a high responsive level at some threshold sodium intake. Nine normal subjects received angiotensin II infusions while in balance on five levels of sodium intake over two orders of magnitude, 3 to 300 mEq sodium per day. Basal plasma renin activity, plasma aldosterone and plasma angiotensin II concentrations gradually fell as dietary sodium intake increased. The adrenal was quite sensitive to the state of sodium balance since a shift in sodium intake of as little as 20 mEq (e.g. 10 to 30 mEq/day) induced a significant change in basal plasma aldosterone. Adrenal responsiveness to infused angiotensin varied inversely with the log of urinary sodium excretion over the entire range of sodium intake, indicating that there is a gradual modulation of adrenal responsiveness with changes in dietary sodium. In addition, despite a constant dietary potassium intake, serum potassium gradually fell from 4.55 +/- .06 to 3.98 +/- .07 mEq/l, (P less than 0.02), as sodium intake increased, partly due to increased urinary potassium excretion (mean cumulative potassium loss of 129 mEq). Thus, changes in potassium balance may be important in modulating the sodium-associated variation in aldosterone secretion. PMID- 3329090 TI - Neuropeptide Y and calcitonin gene-related peptide: effects on glucagon and insulin secretion in the mouse. AB - Neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) are both intrapancreatic neuropeptides that are known to inhibit stimulated insulin secretion. In the present study, we examined their influences on basal and stimulated glucagon and insulin secretion in the mouse. Either NPY or CGRP was injected intravenously at two dose levels (0.85 or 4.25 nmol/kg). When injected alone, neither of them did affect basal plasma glucagon levels but CGRP reduced basal plasma insulin levels. Glucagon secretion stimulated by the cholinergic agonist carbachol was modestly inhibited by NPY at 4.25 nmol/kg (P less than 0.01) but not affected by CGRP. In contrast, glucagon secretion stimulated by the beta 2-adrenoceptor agonist terbutaline was markedly inhibited by NPY already at the lower dose level (P less than 0.01) and potentiated by CGRP (P less than 0.01). Insulin secretion stimulated by carbachol was inhibited by CGRP (P less than 0.01) but not affected by NPY, whereas terbutaline-induced insulin secretion was inhibited by both NPY (P less than 0.05) and CGRP (P less than 0.01). We conclude that the two intrapancreatic neuropeptides NPY and CGRP have opposite actions on stimulated glucagon secretion in the mouse: NPY in an inhibitory and CGRP in a potentiatory direction. Both peptides, however, inhibit insulin secretion stimulated by terbutaline. PMID- 3329093 TI - Somatomedin C/insulin-like growth factor I production by human fetal lung tissue maintained in vitro. AB - The production of somatomedin C/insulin-like growth factor I (Sm-C/IGFI) by human fetal lung tissue maintained in vitro was examined in the present study. We have shown that epithelial cells in human fetal lung explants maintained in vitro differentiate into type II cells within 4-6 days. During the first 24 h of culture, the fetal lung explants released 2.74 +/- 0.14 ng Sm-C/IGFI/mg tissue protein into the culture medium. At this time the explants contained 0.24 +/- 0.02 ng Sm-C/IGFI/mg tissue protein. During the next 4 days of culture, explant Sm-C/IGFI content and the rate of Sm-C/IGFI secretion into the medium declined by approximately 50%. Sm-C/IGFI secretion was inhibited significantly when fetal lung explants were cultured in media that contained cortisol (10(-7) M), a hormone that is known to stimulate fetal lung type II cell differentiation. The effect of cortisol was both concentration- and time-dependent. While insulin, bovine prolactin, and human growth hormone had no apparent effect on Sm-C/IGFI production by the explants, human prolactin and human placental lactogen both decreased Sm-C/IGFI production. These findings are unprecedented and are suggestive that Sm-C/IGFI synthesis may be regulated in a unique fashion in the fetal lung. The decline in Sm-C/IGFI production by fetal lung tissue temporally correlates with the initiation of fetal lung type II cell differentiation in the human fetal lung explants. PMID- 3329092 TI - The effect of substratum and serum on the lipid synthesis and morphology of alveolar type II cells in vitro. AB - To determine the effect of various culture conditions on the maintenance of lipid synthesis and morphology in alveolar type II cells, we cultured isolated adult rat alveolar type II cells on either plastic or denuded human amnionic basement membrane (ABM) in medium supplemented with either fetal bovine, porcine, horse, rat, or human serum. Lipid synthesis was assessed by incubation with [1 14C]acetate and determination of the distribution of radiolabel into individual lipid classes. Cells cultured on ABM incorporated significantly higher percentages of acetate into either phosphatidylcholine (PC) or phosphatidylglycerol (PG), and retained lamellar inclusions and a more characteristic cuboidal shape for longer periods than did cells cultured on plastic. Compared to other sera, cells cultured in the presence of rat serum incorporated the highest percentages of acetate into PC and saturated PC, had the best preservation of lamellar-body ultrastructure, and also appeared to contain more multivesicular bodies. The percent composition of linoleic acid, an essential fatty acid, was found to vary widely among the different sera. Supplementing media with linoleic acid resulted in a marked increase in acetate incorporation into saturated PC and a decreased incorporation into PG. We conclude that for maintenance of differentiated function of adult rat alveolar type II cells in primary culture (1) ABM is preferable to plastic as a culture substratum, (2) rat serum is preferable to fetal bovine serum as a serum supplement, and (3) the regulation of lipid synthesis by linoleic acid causes disparate effects on PG and saturated PC synthesis. PMID- 3329094 TI - Effects of time-variant exposure on toxic substance response. AB - Sources of time-variant exposure to toxic substances are identified and examined for their effects on the estimation of response. It is shown that only time averaged target tissue concentrations are required to obtain rigorous risk estimates from the one-hit and multihit models. In contrast, detailed concentration histories need to be retained throughout analyses involving two event models with intermediate-stage clonal growth advantage (clonal two-stage) and multistage models. Cumulative incidence ratios, based on the exact to time averaged treatment of concentration time dependencies, are evaluated for substances whose toxic responses exhibit moderate (arsenic) and strong (ethylene dibromide) dependence on time of actual exposure. These ratios reveal that time averaged dose approximations may lead to several orders of magnitude error in both the multistage and clonal two-stage models if exposure periods are short, and that 3.4-fold (arsenic) and 8-fold (ethylene dibromide) errors still exist even when an actual two-thirds lifetime exposure is averaged over a full lifetime. Finally, the effects of time-variant exposure on risk estimation due to migration and birth-death in an epidemiological setting are examined. A residence time distribution calculation shows that, if these effects are ignored for a population orally exposed to arsenic and characterized by an out-migration rate in excess of 5%/yr, response errors will exceed an order of magnitude. PMID- 3329095 TI - Human hypervariable sequences in risk assessment: rare Ha-ras alleles in cancer patients. AB - A variable tandem repeat (VTR) is responsible for the hyperallelism one kilobase 3' to the human c-Ha-ras-1 (Ha-ras) gene. Thirty-two distinct restriction fragments, comprising 3 allelic classes by frequency of occurrence, have thus far been detected in a sample size of approximately 800 caucasians. Rare Ha-ras alleles, 21 in all, are almost exclusively confined to the genomes of cancer patients (p less than 0.001). From our data we have computed the relative cancer risk associated with possession of a rare Ha-ras allele to be 27. To understand the molecular basis for this phenomenon, we have begun to clone Ha-ras fragments from nontumor DNA of cancer patients. We report here the weak activation, as detected by transfection and transformation of NIH 3T3 mouse cells, of two Ha-ras genes which were obtained from lymphocyte DNA of a melanoma patient. We have mapped the regions that confer this transforming activity to the fragment containing the VTR in one Ha-ras clone and the fragment containing gene coding sequences in the other. PMID- 3329096 TI - Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts. AB - Ethylene dibromide (1,2-dibromoethane, EDB) can be activated to electrophilic species by either oxidative metabolism or conjugation with glutathione. Although conjugation is generally a route of detoxication, in this case it leads to genetic damage. The major DNA adduct has been identified as S-[2-(N7 guanyl)ethyl]glutathione, which is believed to arise via half-mustard and episulfonium ion intermediates. The adduct has a half-life of about 70 to 100 hr and does not appear to migrate to other DNA sites. Glutathione-dependent DNA damage by EDB was also demonstrated in human hepatocyte preparations. The possible relevance of this DNA adduct to genetic damage is discussed. PMID- 3329097 TI - Nearest neighbor affects G:C to A:T transitions induced by alkylating agents. AB - The influence of local DNA sequence on the distribution of G:C to A:T transitions induced in the lacI gene of E. coli by a series of alkylating agents has been analyzed. In the case of nitrosoguanidine, two nitrosoureas and a nitrosamine, a strong preference for mutation at sites proceeded 5' by a purine base was noted. This preference was observed with both methyl and ethyl donors where the predicted common ultimate alkylating species is the alkyl diazonium ion. In contrast, this preference was not seen following treatment with ethylmethanesulfonate. The observed preference for 5'PuG-3' site over 5'-PyG-3' sites corresponds well with alterations observed in the Ha-ras oncogene recovered after treatment with NMU. This indicates that the mutations recovered in the oncogenes are likely the direct consequence of the alkylation treatment and that the local sequence effects seen in E. coli also appear to occur in mammalian cells. PMID- 3329098 TI - Long-term treatment of rheumatoid arthritis: results of a two-year study with tenoxicam. PMID- 3329099 TI - Double-blind study of tenoxicam 20 mg versus piroxicam 20 mg in rheumatoid arthritis. PMID- 3329100 TI - A long-term, double-blind, comparative study of tenoxicam (Ro 12-0068) and piroxicam in gonarthrosis and coxarthrosis. PMID- 3329102 TI - Long-term treatment with tenoxicam in rheumatoid arthritis. PMID- 3329101 TI - Tenoxicam (Ro 12-0068) in patients with extra-articular rheumatism. PMID- 3329103 TI - Tenoxicam (Ro 12-0068) in ankylosing spondylitis. PMID- 3329104 TI - Long-term study with tenoxicam (Ro 12-0068) in the treatment of gonarthrosis and coxarthrosis. PMID- 3329105 TI - Double-blind parallel study of tenoxicam (20 mg vs. 40 mg) in extra-articular inflammation. PMID- 3329106 TI - Use of tenoxicam in patients with acute gouty arthritis. PMID- 3329107 TI - Overview on the pharmacokinetics of tenoxicam. AB - Tenoxicam, a new non-steroidal anti-inflammatory drug (NSAID) with an oxicam structure, is entirely ionised at physiological pH, has minimal lipophilic properties, high plasma protein binding, does not accumulate in fatty tissue and skin and thus has a small volume of distribution. Tenoxicam is rapidly and completely absorbed after oral administration. It is entirely metabolised via oxidation and conjugation pathways before elimination. The extraction ratio in the liver is small resulting in a long elimination half-life with a mean of 72 hours. Since no unchanged drug is found in the bile the low half-life cannot be explained by enterohepatic recirculation of parent compound. The low elimination rate of tenoxicam allows for a once-daily dosage (20 mg) regimen. Following multiple dosing during the first two weeks of therapy tenoxicam reaches steady state levels within 10-20% of predicted values. Several pharmacokinetic factors help make tenoxicam therapy safe and straightforward: it is completely absorbed when taken orally even with meals or antacids, it penetrates easily into synovial fluid, and is excreted as inactive metabolites. Furthermore, drug disposition is not influenced by age, sex or rheumatic disease and unexpected accumulation is not observed. PMID- 3329108 TI - Evaluation of tenoxicam in rheumatology--clinical trial results in Argentina and Brazil. AB - The therapeutic activity of tenoxicam, a thienothiazine derivative with analgesic and anti-inflammatory properties, has been studied by 15 investigators in Argentina and Brazil. Twenty-nine clinical trials were performed in a total of 747 patients suffering from rheumatoid arthritis (270), cox- and gonarthrosis (190), extra-articular inflammation (250) and acute gout (37). Out of the patients studied, 507 received tenoxicam and 240 were given comparative preparations. In 76% of the patients 20 mg tenoxicam was given as a single daily dose. In most patients duration of treatment was either six weeks or six months. Therapeutic results were evaluated according to the evolution of pain in various conditions as well as that of the articular, clinical and functional status. Once treatment was concluded a global evaluation of efficacy and tolerance was performed. The statistical analysis showed a significant improvement, in comparison to baseline, in all parameters considered under the different conditions. Double-blind studies showed no significant statistical differences between tenoxicam and the comparative preparations. Tolerance to tenoxicam was considered excellent, granting that some patients referred to adverse effects of the gastrointestinal type, such as epigastric discomfort, pyrosis and flatulence of moderate intensity. Tenoxicam is a new non-steroidal anti-inflammatory compound which is well tolerated and has excellent activity in the treatment of diverse rheumatoid conditions. PMID- 3329109 TI - Efficacy and tolerability of tenoxicam--an overview. AB - One-hundred and thirty-three clinical studies have been conducted with tenoxicam in patients with rheumatoid arthritis, osteoarthrosis, extra-articular rheumatism, ankylosing spondylitis and acute gouty arthritis. Its efficacy has been demonstrated in double-blind comparative studies against placebo, and dose finding studies have found the optimal dose to be 20 mg. Most trials comparing tenoxicam with another NSAID have used piroxicam, an earlier oxicam derivative which also has a long half-life. In general, efficacy was similar in both drugs with a trend in favour of tenoxicam. The tolerability of tenoxicam has also been studied in detail. In short-term studies 11% of patients receiving 20 mg tenoxicam and 18% on 40 mg tenoxicam experienced side-effects (p less than 0.01), as did 20% treated with 20 mg piroxicam (p less than 0.01 against 20 mg tenoxicam). In long-term studies clinical tolerability of 20 mg tenoxicam was found to be superior to that of 20 mg piroxicam. The types of side-effects encountered were mainly gastrointestinal disturbances, followed in frequency by skin rashes. However, all side-effects were generally mild and reversible. The efficacy of tenoxicam is clearly established and its tolerability is acceptable with a 20 mg dose. Tenoxicam thus seems a promising drug and a useful addition to the therapeutic armamentarium. PMID- 3329111 TI - Double-blind, parallel clinical trial of tenoxicam (Ro 12-0068) versus piroxicam in patients with ankylosing spondylitis. PMID- 3329110 TI - A long-term randomised trial on tenoxicam and piroxicam in osteoarthritis of the hip or knee: a 24-month interim report focusing on the 12-24 month interval. AB - The long-acting antiphlogistics tenoxicam (Ro 12-0068, Tilcotil) and piroxicam in single daily oral doses of 20 mg are compared in a double-blind, group comparative, randomised trial planned to last for five years. Results of 12 months' treatment of 108 patients with osteoarthritis of the hip or knee have been reported. This interim analysis focuses mainly on the 12 to 24 month interval. The clinical improvements obtained within the first 12 months persisted during the second year in the 55 patients remaining on treatment. After 24 months, 53 patients had been withdrawn prematurely, three-quarters because of inefficacy or intolerance. Only six patients were withdrawn between 12 and 24 months, three for lack of efficacy, two for side-effects and one for reasons unrelated to therapy. There was no difference between the treatment groups with regard to incidence, time or reason for withdrawal, and only small, insignificant differences in efficacy and tolerability. This trial shows that long-term treatment of osteoarthritis with tenoxicam and with piroxicam is beneficial. Once efficacy and tolerability have been established, maintenance of therapy is feasible. PMID- 3329112 TI - Clinical, double-blind long-term study of tenoxicam 20 mg (Ro 12-0068) versus piroxicam 20 mg in patients with gonarthrosis. PMID- 3329113 TI - Tenoxicam or diclofenac in the treatment of gonarthrosis. PMID- 3329115 TI - Long-term study with tenoxicam in rheumatoid arthritis. PMID- 3329114 TI - Tenoxicam in the treatment of extra-articular inflammatory processes. PMID- 3329116 TI - Tenoxicam, a new non-steroidal anti-inflammatory drug in the prolonged treatment of rheumatoid arthritis. PMID- 3329117 TI - Comparative evaluation of tenoxicam and piroxicam in the treatment of humeroscapular periarthritis. PMID- 3329118 TI - Symptomatic long-term treatment of arthrosis with tenoxicam. PMID- 3329119 TI - Determination of glycated plasma proteins in normal and diabetic subjects utilizing aminophenylboronic acid columns. AB - The characteristics and clinical utility of a commercially prepared method for measuring glycated plasma proteins (glyc PP) by aminophenylboronic acid affinity chromatography is described. The measured glyc PPs after loading columns with 0.05 ml (5.9%) or 0.025 ml (6.1%) plasma were greater than the glyc PP values when using 0.20 ml (4.5%) or 0.10 ml (5.0%). The glyc PPs in otherwise identical plasma containing 0, 1 gm/l, 2 gm/l and 4 gm/l glucose were not significantly different. Elimination of the aldimine component by dialyzing plasma against saline did not alter the amount of glyc PP. In vitro glycosylation of plasma proteins was dependent on glucose concentration and length of incubation. Maximum in vitro glycosylation (19.5%) occurred at 14 days of incubation with 5.7 gm/l glucose. The mean glyc PP (8.2%) of 24 diabetic subjects was greater than the mean glyc PP (2.7%) of 15 normal controls. Glyc PP and HbA1 values positively correlated (n = 39 r = 0.89 p less than 0.01). After 2 weeks of improved glycemic control, the glyc PPs from 5 patients diminished from 6.8% to 3.3% (p less than 0.01). In conclusion, we characterize an aminophenylboronic acid affinity chromatographic method of assaying glyc PP which is simple, reproducible, requires a maximal protein load of 0.05 mg, is uneffected by ambient glucose, and measures the ketoamine composent of glyc PP. This is an ideal method to evaluate 2 week alterations of glycemic control of diabetic patients. PMID- 3329120 TI - Insulin clearance and microsomal glutathione-insulin transhydrogenase in perfused livers of fed and fasted rats. AB - Clearance of exogenous insulin measured in perfused livers from rats fed ad lib or fasted X 24 or X 48 h was correlated with changes in activity and distribution of the insulin-degrading enzyme glutathione-insulin transhydrogenase measured in microsome fractions, post-perfusion. For comparison with endogenous insulin removal (Endocr. Res. Commun. 7: 231, 1980), a single-pass perfusion mode was used and clearance of insulin at levels (less than or equal to 15 ng/ml) typically observed in perfused rat liver-pancreases during glucose stimulation was studied. Similar to the endogenous data, exogenous insulin removal followed an ogival pattern during fasting. In the fed state, clearance was relatively low, corresponding to a hepatic extraction of approximately 29%. Insulin extraction increased nearly 2-fold after a 24 h fast to approximately 48% (p less than .01), declining to approximately 30% (p less than .025) when fasting was prolonged (X 48 h). At portal insulin concentrations greater than 8 ng/ml (approximately 200 microUnits/ml), clearance tended to decrease in all 3 nutritional states, with apparent saturation of the insulin capturing mechanism being strongest in the 24 h fasted state. In conjunction with these changes in whole organ insulin removal, GSH-insulin transhydrogenase nonlatency, viz., nonlatent activity in intact microsomes relative to total activity in disrupted microsomes, did not change during the first 24 h of fasting; whereas the proportion of nonlatent activity was significantly decreased (p less than .01) after 48 h. Homogenate activity remained essentially constant during the initial fasting period, and declined by approximately 16% (p less than .01) after 48 h of fasting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3329121 TI - Inhibitory effects of metformin on insulin and glucagon action in rat hepatocytes involve post-receptor alterations. AB - The effect of the hypoglycaemic biguanide, metformin, on insulin binding and insulin action was investigated in rat hepatocyte monolayers. The binding of insulin was not modified in cultured cells exposed for 24 or 48 h to metformin at concentrations ranging from 1 mumol/l to 1 mmol/l, and no effect could be detected on insulin-induced down regulation. Metformin did not alter insulin stimulation of amino acid transport but the stimulatory effect of insulin on glycogen synthesis was reduced by 20%, 30% and 63% for metformin at 0.01, 0.1 and 1 mmol/l, respectively. Both responsiveness and sensitivity were altered by the biguanide. Metformin also inhibited basal glycogen synthesis and cellular glycogen contents were markedly decreased after exposure of cells to metformin (0.01-1 mmol/l). We also investigated the effect of metformin on glucagon action and metformin (0.1-1 mmol/l) was found to decrease the stimulatory effect of glucagon on amino acid uptake and on gluconeogenesis from alanine. These inhibitory effects of the biguanide were still observed when glucagon was replaced by dibutyryl cAMP. These in vitro studies demonstrate that: 1) metformin has no direct effect on insulin binding in hepatocytes, indicating that alteration of insulin stimulation of glycogen synthesis is due to modifications at the post receptor level. 2) metformin alters the action of glucagon in hepatocytes at a post AMP cyclase step. They also suggest that one of the mechanism of action of metformin may be to antagonize the effect of glucagon rather than to potentiate the action of insulin. PMID- 3329122 TI - Prolonged weight loss with dexfenfluramine treatment in obese patients. AB - 17 patients with refractory obesity, who had gained an average of 0.7 +/- 1.9 kg during 12 weeks treatment with diet and placebo, lost a mean of 2.9 +/- 0.5 kg after 12 weeks sequential treatment with dexfenfluramine 15 mg twice daily (p less than 0.001). In a second trial, 29 patients were treated for 24 weeks with dexfenfluramine; average cumulative weight loss after 12 weeks in these patients (5.7 +/- 0.1 kg) was significantly greater than in the patients who had been treated initially with placebo. After 24 weeks of dexfenfluramine treatment there was a further significant increase in cumulative weight loss (7.0 +/- 0.8 kg; p = 0.05). The incidence of side effects in both trials was lower than that reported in previous studies of racemic dlfenfluramine. The clinically significant weight loss, and low incidence of unwanted effects, suggest that dexfenfluramine has a role in the treatment of refractory obesity. PMID- 3329123 TI - Glucose and insulin responses to meals containing milk, lactose, glucose or fructose in subjects with non-insulin-dependent diabetes. AB - The postprandial blood glucose and serum insulin responses to liquid test meals containing 40 g carbohydrate from milk, lactose, glucose or fructose and equal amounts of energy were compared in 10 non-insulin-dependent (type 2) diabetic patients. The meals were consumed in random order on consecutive days after an overnight fast. Significant differences (p less than 0.001, ANOVA) were observed between the glucose and insulin responses to the meals. The glucose response was significantly higher after the glucose containing meal and lower after the fructose meal as compared with the other meals. The insulin response was significantly higher after the lactose and glucose meals than after the milk and fructose meals. After the milk and lactose meals the blood glucose responses were similar whereas the insulin response was significantly lower after the milk meal. As lactose apparently was similarly absorbed from the two meals the difference in the insulin response was probably due to different insulinogenic effects of the protein components or to differences in the physical properties of the respective meals. PMID- 3329124 TI - Insulin receptor binding to monocytes and erythrocytes in gestational diabetes. AB - Insulin receptor binding to monocytes and erythrocytes was measured at the time of diagnosis and again postpartum in 23 normal weight gestational diabetics. In 16 women, insulin receptor binding was studied after a period of dietary treatment. In patients diagnosed early in pregnancy, an increase in insulin binding to both monocytes and erythrocytes was observed during dietary treatment (p less than 0.001), while no similar changes were observed in patients diagnosed later in pregnancy. Postpartum, insulin receptor binding to erythrocytes decreased in all women compared to the time of diagnosis (p less than 0.01) while insulin binding to monocytes either decreased (p less than 0.001) or remained unchanged depending on the time of diagnosis. Insulin binding was similar in those women who remained glucose intolerant and those who returned to normal glucose tolerance postpartum. The findings indicate that factors other than insulin receptor binding are involved in the pathogenesis of gestational diabetes. PMID- 3329125 TI - [Value of combined subcutaneous infusion of insulin and metformin in 10 insulin dependent obese diabetics]. AB - Combined continuous subcutaneous insulin infusion (CSII) and metformin (M) was tested in 10 overweighted insulin requiring diabetic patients (body mass index 27.9 +/- 4.9 kg/m2). They were still poorly controlled (HbA1 9.6 +/- 0.8%) despite large doses of lente insulin (Novo) (51.7 +/- 19.6 IU/24 h) injected once daily. With CSII after two weeks on placebo (P) they were enrolled in a randomized double blind cross-over trial with two successive one month periods of M (2550 mg/day) or P. At the end of the two-weeks period CSII--initial P, the daily regular insulin requirement decreased significantly (40.1 +/- 18.1). During M and P body weight and HbA1 were unchanged (respectively 28.6 +/- 6.0 vs 29.0 +/ 59 kg/m2 and 7.7 +/- 1.1 vs 7.7 +/- 0.8%). With M daily insulin requirements decreased significantly (32.0 +/- 16.8 vs 38.4 +/- 18.2 IU, p less than 0.05). During test-meals, M compared to placebo also reduced peripheral free insulin concentrations (-24.9 +/- 26.0%) while plasma glucose and C peptide remained comparable. In the conditions of this study, combined CSII and M reduced the insulin resistance observed in overweighted insulin requiring diabetic patients. PMID- 3329126 TI - Effect of the addition of simple sugars to mixed meals on the glycemic control of insulin treated diabetic patients. AB - In order to evaluate the long term effects of a daily intake of simple sugars upon the glycemic control, 10 insulin treated diabetic outpatients received, according to a randomized cross over design, a conventional or a sucrose-enriched isocaloric, isoglucidic diet (about 20 g sucrose per day, given as desserts and/or soft drinks during or after mixed meals) for 3 months each. The daily insulin doses remained identical during both diets: 0.58 +/- 0.07 vs 0.58 +/- 0.06 U/kg body weight (mean +/- SEM) after conventional and sugar-enriched diet, respectively. The percentages of short acting insulin were also similar: 50 +/- 4 vs 49 +/- 4%. The mean glycemic profiles after lunch and dinner were comparable with both regimens. Moreover, glycosylated hemoglobin levels were 10.0 +/- 0.3 vs 9.9 +/- 0.4% after conventional and sucrose enriched diet, respectively. Plasma cholesterol and triglycerides remained unchanged. In conclusion, a relatively small daily intake of sucrose for 3 months has no clinical and/or metabolic side effects. Therefore, it seems no longer justified to completely ban sucrose from the diet of diabetic patients. PMID- 3329127 TI - Dietary control of protein turnover. AB - The balance between protein synthesis and breakdown (protein turnover) regulates whole-body protein mass. The relationships between dietary changes (amount and composition of food) and protein synthesis, protein breakdown and amino acid oxidation have been explored in order to better understand adaptations of protein and amino acid metabolism. Methods for measuring protein synthesis, especially whole-body protein synthesis, can be divided into two groups: the 15N end-product method (urea and/or ammonia), and the incorporation of labelled amino acid(s) into proteins. Assumptions and limitations of the widely used two-pool model (free amino acid and protein pools) are discussed. Results obtained with different methods and for amino acids have been compared, to assess their ability to detect changes in protein synthesis rates. Methods of measuring protein breakdown have also been described briefly. Food intake affects whole-body and tissue protein turnover throughout development of animals and humans in different ways. Protein metabolism fluctuates during the 24-hour period in response to intermittent food intake. During the post-prandial period, a net whole-body protein deposition occurs. This is essentially due to increased protein synthesis. The free amino acid pool and amino acid oxidation rates also increase. Consequently, amino acids are used to a great extent as energy substrates. In contrast, a decrease in protein breakdown could enhance protein deposition. During fasting, the rates of whole-body protein synthesis are lower than those of protein breakdown. This results in protein loss, essentially because the drop in protein synthesis rate in muscle is pronounced. N balance is controlled by the amounts and composition of the diet and by changes in protein synthesis and breakdown. Increasing food intake above levels of energy equilibrium can produce growth by enhancing both the whole-body protein synthesis and breakdown rates. Below energy equilibrium, whole-body protein loss occurs because of decreased protein synthesis which becomes lower than protein breakdown. Protein synthesis rate is the main factor controlling N balance in response to alterations in food intake. Increasing dietary protein, especially the essential amino acids, involves increased rates of whole-body protein synthesis and breakdown. The improved N balance obtained by enhancing dietary non-protein energy (carbohydrate, fat) can be brought on by reducing amino acid oxidation and slightly increasing protein synthesis. The effects of dietary protein and energy on protein turnover are apparently additive. PMID- 3329130 TI - [The arthroses]. PMID- 3329129 TI - [The insulin injection pen: gadget or therapeutic progress?]. PMID- 3329128 TI - [New antihypertensive therapy in diabetics]. AB - According to the W.H.O. criteria (160/95 mmHg), arterial hypertension is present in about one third of diabetic patients. But the W.H.O. criteria are not appropriate in insulin-dependent diabetics. There is increasing evidence that a slight increase of blood pressure values may have a deleterious effect on various localizations of diabetic angiopathy. Arterial blood pressure is a major predictive factor for stroke or death due to coronary heart disease. The incidence and prevalence of diabetic retinopathy are significantly correlated with systolic and/or diastolic blood pressure values. In patients with incipient diabetic nephropathy, a slight elevation of blood pressure values is usually observed, an antihypertensive treatment may reduce albumin excretion rate and may prevent clinical diabetic nephropathy. Antihypertensive treatment is the more effective and the best tolerated of all interventions dedicated to reduce albumin excretion. Calcium antagonists and angiotensin converting enzyme inhibitors are at the present time the drugs to be used in the treatment of hypertensive diabetic patients as they are more effective and better tolerated than the usual antihypertensive agents. A part from their antihypertensive effect, they also improve cardiac, cerebral and intra-renal haemodynamics. PMID- 3329131 TI - [Blood insulin and arterial pressure in patients with chronic uremia in hemodialysis]. PMID- 3329134 TI - [Basic concepts of today's immunology (2)]. PMID- 3329133 TI - [Consequences of pancreatectomy in a patient with type 2 diabetes mellitus (non insulin-dependent). Clinico-therapeutic aspects]. PMID- 3329132 TI - [Wegener's granulomatosis. Review of the literature and description of a case]. PMID- 3329135 TI - [Thrombocytopenia caused by drugs: new molecules as the cause]. PMID- 3329136 TI - [Gastric lesions caused by anti-inflammatory drugs]. PMID- 3329137 TI - [Alkaline phosphatase]. PMID- 3329138 TI - [Digitalis therapy]. PMID- 3329139 TI - [Acquired immunodeficiency syndrome (AIDS)]. PMID- 3329140 TI - [Nutritional analysis and diet therapy: the role of computers]. PMID- 3329141 TI - [Pharmacologic treatment of senile mental deterioration]. PMID- 3329142 TI - Reduced insulin secretions in acute myocarditis produced by scorpion (Buthus tamulus) venom injection in rabbits. PMID- 3329143 TI - Cor pulmonale. PMID- 3329144 TI - [Infectious balanoposthitis and "erythroplastic" balanoposthitis. Review of cases for the years 1983-1984]. PMID- 3329145 TI - [Flier's syndrome: an autonomous entity?]. PMID- 3329146 TI - [Histiocytosis X. A case with unusual clinical polymorphism]. PMID- 3329147 TI - [Gonococcal urethritis and cervicitis: microbiological studies]. PMID- 3329148 TI - [Cutaneous manifestations in kidney transplant patients. 2 cases of Kaposi's sarcoma]. PMID- 3329150 TI - [Treatment of induratio penis plastica with intralesional infiltration of orgotein. Our experience in 5 cases]. PMID- 3329149 TI - [Controlled study of the efficacy of topical immunotherapy in alopecia areata: squaric acid versus placebo]. PMID- 3329151 TI - Physiological development of the infant and its implications for complementary feeding. PMID- 3329152 TI - Decalcified freeze-dried bone allografts: a successful procedure in the reduction of intrabony defects. PMID- 3329153 TI - Diagnostic dilemma: to bond, laminate, or crown? PMID- 3329154 TI - The dorsal skin-fold preparation of awake Syrian golden hamsters for assessment of microvascular permeability and microhaemodynamics with leukotriene C4. AB - This study has quantitated the effects of topically-applied leukotriene C4 (LTC4) upon vessel diameters, red blood cell velocities and vascular permeability to macromolecules in an animal model, namely, the dorsal skin-fold preparation of Syrian golden hamsters. Furthermore, we studied the efficacy of the leukotriene receptor blocking agent FPL 55712 in this preparation in order to establish a model for testing antiinflammatory compounds possibly involved in the lipoxygenase cascade. PMID- 3329155 TI - Changes in serum insulin levels during orthotopic liver transplantation in the pig. AB - Insulin and glucose levels were measured in 13 orthotopic liver transplantations in pigs. After portal revascularization a significant increase in the glucose levels takes place (p less than 0.01). When the infrahepatic vena cava clamp is removed, a significant increase in glucose and insulin concentrations (p less than 0.05) takes place. After the end of the operation the insulin levels decrease significantly with respect to initial values (p less than 0.05). PMID- 3329156 TI - Technique and endoscopic monitoring of the healing process in bilioenteric anastomoses. AB - Thirty-three patients were given cholangiojejunoanastomoses: 13 for benign postoperative stenoses of the biliary tract (BT) with or without lithiasis; five for massive intra and extra-hepatic lithiasis; 15 for malignant stenoses on the upper third of the biliary ways. The 15 patients in Group A were given a muco mucosal anastomosis and the 18 in Group B extramucosal anastomosis after excision of the excess mucosa on the jejunotomy. In both groups an interrupted suture using fine, slow-absorption thread was employed. Three patients (two from Group A and one from Group B) were excluded from the study due to postoperative filtration of the anastomosis. Transhepatic cholangioscopic monitoring of the healing process on the 15th, 20th, 30th and 40th day showed that while both types of anastomosis were equally secure, the extramucosal suture after excision of excess mucosa produced wider anastomoses and is therefore advisable in all cases of bilioenteric anastomosis (BEA) but especially when the biliary ways are narrow or tendentially thin-walled. PMID- 3329157 TI - Autorenal transplantation in the treatment of renovascular hypertension. AB - Autorenal transplantation was performed on 32 renal units including three bilateral transplants, in 29 renovascular hypertensive patients. Aortoarteritis in 18, fibromuscular dysplasia in six, and atherosclerosis in five were the causative renal arterial lesions. Young patients with severe or uncontrolled hypertension but with functioning kidneys were selected for this procedure. Follow-up varied from one to seven years. Twenty-two patients were cured of hypertension, four showed improvement and in three the transplanted kidneys failed to function due to vascular thrombosis postoperatively. There was no death in the series. PMID- 3329158 TI - Minor liver resection guided by echography. PMID- 3329159 TI - Isis at seventy-five. PMID- 3329160 TI - Darwin's Malthusian metaphor and Russian evolutionary thought, 1859-1917. PMID- 3329161 TI - Tissue CEA as prognostic indicator in a series of 44 cases of colorectal cancer. AB - The role of tissue CEA determination as a complementary test in the staging of colorectal cancer and monitoring of the marker in the follow-up of patients, is stressed. In a group of 44 colorectal cancer patients, tissue CEA was determined by the immunoperoxidase assay in the apical and cytoplasmic portion of tumor cells, stroma, glandular lumen, and cytoplasm of superficial and deep cells. A correlation has been observed between spread and stage of tumor and CEA localization at the level of the stroma and cytoplasm of deep cells. It has been also evidenced that in all cases where CEA was present in the stroma and cytoplasm of deep cells, high serum levels of the marker were detected. PMID- 3329162 TI - Clinical, biochemical and ultrasonographic findings of choledochal sphincteroplasty. A 1 to 14 year follow-up study. AB - Sixty patients, who underwent choledochal sphincteroplasty and then yearly referred to the department for a diagnostic check-up, entered this study. Follow up ranged from 1 to 14 years after surgery. Check-up examination included: 1) clinical assessment, 2) serum liver and pancreas function tests, and 3) ultrasonography. Good long-term clinical results were obtained in 50 cases. Seven patients complained of mild and temporary hepatic symptoms or digestive troubles. Three subjects developed severe symptoms: jaundice, fever, pain or ascites. The causes of the failures were: 1) recurrent stones in the distal portion of the common bile duct with cholangitis, 2) common hepatic duct stricture with recurrent stones and cholangitis, and 3) alcoholic cirrhosis. The following conclusions may be drawn: 1) Sphincteroplasty achieved a fourteen year success rate of 90% 2) Cholangitis, which supervened in 2 patients, was associated with bile duct strictures and recurrent stones. 3) The great majority of patients who had undergone sphincteroplasty, showed normal size of the bile ducts. However, 10% of patients still retained some degree of intrahepatic ductal dilatation. 4) Since recurrent bile duct stenoses occurred as far as 6 and 8 years after surgery, long-term follow-up is mandatory. PMID- 3329163 TI - Biologic catalysis by RNA. PMID- 3329164 TI - Why study the cytoskeleton in yeast? PMID- 3329165 TI - Anion-exchange and glucose transport proteins: structure, function, and distribution. PMID- 3329166 TI - Mechanisms of human beta-interferon gene regulation. PMID- 3329167 TI - Pituitary metastasis: lung cancer presenting as bitemporal hemianopsia with diabetes insipidus and anterior pituitary deficiency. PMID- 3329169 TI - Naltrexone does not affect adrenal steroidogenesis in women with hirsutism/oligomenorrhea. PMID- 3329168 TI - Prolonged remission of Cushing's disease following bromocriptine therapy. PMID- 3329170 TI - Neurobehavioral symptoms in mild primary hyperparathyroidism: related to hypercalcemia but not improved by parathyroidectomy. PMID- 3329172 TI - An overview of magnetic resonance imaging of the appendicular musculoskeletal system. PMID- 3329173 TI - Management of extramedullary plasmacytomas. PMID- 3329171 TI - Effects of weight reduction, exercise, and diet modification on lipids and apolipoproteins A-1 and B in severely obese persons. PMID- 3329174 TI - T-cell lymphoma in renal transplant recipient. PMID- 3329175 TI - Obstructing giant pseudopolyposis of the colon in ulcerative colitis. PMID- 3329176 TI - Melvin A. Block, MD. PMID- 3329177 TI - A new secured technique for suprahepatic vena caval anastomosis in porcine liver transplantation. PMID- 3329178 TI - Lessons from the anemia of prematurity. AB - In our view, three main lessons stem from consideration of the refractory early anemia of prematurity (REAP). These are: (1) Hemoglobin concentration is not enough to describe the anemia. (2) The REAP may be clinically very severe but is often easily missed. It interacts with and worsens other causes of anemia in preterm infants, such as blood losses. Its pathogenesis is multifactorial, but it is generally interrelated with short gestation and its other complications. (3) Prevention, prophylaxis, and if necessary, adequate management are very important. PMID- 3329179 TI - New insights on vitamin K. AB - Vitamin K catalyzes the post-translational carboxylation of coagulation proteins C, S, and factors II, VII, XI, and X. Detection of the noncarboxylated forms allows an indirect and specific measure of the vitamin K deficiency found in early, classic, and late hemorrhagic disease of the newborn (HDN), malabsorption syndromes, and drug related (warfarin, anticonvulsants, and antibiotics) states. Idiopathic late HDN (CNS bleeding) occurs in exclusively breast-fed infants and is prevented by appropriate parenteral and oral vitamin K prophylaxis given at birth. All newborn infants and older infants with malabsorption syndromes should receive prophylactic vitamin K. PMID- 3329181 TI - The diagnostic utility of measurements of erythrocyte porphyrins. AB - This article summarizes the diagnostic usefulness of measurements of erythrocyte porphyrins in several hematologic conditions, including lead poisoning, iron deficiency, and sickle cell anemia. It discusses the various available methods and their validity in the diagnosis of hematologic disorders and abnormalities of porphyrin metabolism. PMID- 3329180 TI - Human immunodeficiency virus (HIV) infection in children. AB - HIV infection in pediatric patients is a multisystem chronic disease that manifests as a clinical spectrum from asymptomatic infection through symptomatic infection with opportunistic infections and malignancies. The hematopoietic system is involved early in the systemic manifestations of this disease. The hematologic abnormalities seen are most probably a reflection of persistent viral infection, inflammation, and immune dysregulation, and may be complicated by secondary infections, chronic disease, drug toxicities, and nutritional deficiencies. Anemia and lymphopenia are commonly found in adult AIDS patients. Although both are also seen in pediatric patients, lymphopenia is much less common. Atypical lymphocytes with plasmacytoid characteristics have been identified in both adults and children. Pediatric bone marrow evaluation has shown an increase in plasma cells and plasmacytoid lymphocytes. Besides these findings, adult marrow findings include an increase in reticulum and lymphocytes appearing in a diffuse or aggregate pattern. PMID- 3329183 TI - Suggested guidelines for the treatment of children with sickle cell anemia. AB - It is the purpose of this article to provide guidelines used in our sickle cell center for the treatment of several frequent medical complications that occur in children with sickle cell anemia. PMID- 3329182 TI - Behavioral alterations in iron deficiency. AB - This review has examined recent evidence from human studies that iron deficiency adversely affects behavior by impairing cognitive function, producing noncognitive disturbances, and limiting activity and work capacity. The body of research taken as a whole provides increasingly persuasive arguments for intensifying efforts to prevent and treat iron deficiency anemia. Cognitive Function. There is reasonably good evidence that mental and motor developmental test scores are lowered among infants with iron deficiency anemia. Although the research on cognitive function in iron-deficient older children and adults is sparse and diverse, it suggests that there may be alterations in attentional processes associated with iron deficiency. Iron therapy has not yet been shown effective in completely correcting the observed disturbances. Although some aspects of cognitive function seem to change with iron therapy, lower developmental, IQ, and achievement test scores have still been noted after treatment. Noncognitive Disturbances. A variety of noncognitive alterations during infant developmental testing has also been observed, including failure to respond to test stimuli, short attention span, unhappiness, increased fearfulness, withdrawal from the examiner, and increased body tension. Exploratory analyses suggest that such behavioral abnormalities may account for poor developmental test performance in infants with iron deficiency anemia. These studies indicate the fruitfulness of examining noncognitive aspects of behavior, such as affect and activity, in addition to specific cognitive processes. Activity and Work Capacity. There has been a steady accumulation of evidence that iron deficiency anemia limits maximal physical performance, submaximal endurance, and spontaneous activity in the adult, resulting in diminished work productivity with attendant economic losses. The mechanisms underlying these effects, the extent to which anemia or iron deficiency separate from anemia is responsible, and the counterpart in infants and children remain to be established. PMID- 3329184 TI - Thalassemia syndromes. Recent advances. AB - Laboratory and clinical investigators in the past several years have provided many advancements in the understanding of the thalassemia syndromes and in the care of affected patients. The diversity of genetic defects causing thalassemia has been extensively explored, with major benefits to our knowledge of normal globin gene function and of the consequences of specific mutations. In addition, the use of molecular biology methods in these studies has provided major advances in population genetics, gene transfer, and prenatal diagnosis of thalassemia. In the clinical area, guidelines for transfusion, splenectomy, prevention of postsplenectomy infection, and effective iron chelation have been considerably improved, and bone marrow transplantation is now available as an alternative means of treatment. Despite these advances, a great deal remains to be done in the areas of understanding the developmental regulation of globin gene expression, effective gene transfer, oral chelation therapy, safer blood products, and other important areas that will benefit patients afflicted with thalassemia. PMID- 3329185 TI - Management of iron overload in the pediatric patient. AB - Iron overload is a major complication of long-term transfusion therapy. In the absence of treatment, the excessive iron causes diffuse organ damage, usually culminating in death from heart disease. Deferoxamine, an iron-chelating drug, removes tissue iron, prevents iron-induced organ dysfunction, and prolongs life. Proper administration of deferoxamine requires careful attention to dose, route and duration of administration, and compliance. Better chelators are needed but are unlikely to be available soon. Other methods for preventing or reducing iron accumulation involve alterations in the transfusion program or the blood product. Prevention of iron overload should improve the lives of patients with transfusion dependent anemias and extend the usefulness of transfusion in chronic hematologic disorders. PMID- 3329187 TI - [The value of transfontanelle echography in early complications of neonatal bacterial meningitis]. PMID- 3329186 TI - [Hepatobiliary involvement of histiocytosis X: apropos of a case report. Echographic study and review of the literature]. PMID- 3329188 TI - The comparative impact of real time ultrasound and mammography in the diagnosis of T0T1 and T2T4 breast tumors. PMID- 3329189 TI - Importance of imaging in treatment planning. PMID- 3329190 TI - [Indications and limitations of pelvic ultrasonography in young girls]. PMID- 3329192 TI - Tuberculous peritonitis. PMID- 3329193 TI - Radiological diagnosis of abdominal disease. PMID- 3329191 TI - A complicated case of mesosigmoid fibrosarcoma. PMID- 3329194 TI - Postoperative fluid collection after renal transplantation. PMID- 3329195 TI - Self association of Streptomyces subtilisin inhibitor: sedimentation equilibrium and 1H NMR studies. AB - The self association of Streptomyces subtilisin inhibitor, a dimeric protein molecule of MW 23,000 in an aqueous environment has been investigated by the combined use of sedimentation equilibrium analysis and 1H nuclear magnetic resonance (NMR) spectroscopy. A significant degree of self association was found using the sedimentation equilibrium method in the concentration range between 5 and 20 mg/ml. Furthermore, the use of 1H NMR spectroscopy in conjunction with the sedimentation equilibrium method enabled us to study the self association in a much higher concentration range (up to 60 mg/ml or more). The self association reaction in the concentration range of 10-40 mg/ml fits reasonably well a "successive polymerization model" in which each step of the polymerization reaction consists of the addition of one intrinsic dimer of Streptomyces subtilisin inhibitor to the previously formed polymeric species, with an equilibrium constant common to all the steps of 400 M-1. The 1H NMR chemical shift and line broadening data show that the dimer-dimer interaction probably involves the reactive-site segment of this inhibitor without a significant conformational change in the major part of the protein structure. PMID- 3329196 TI - Affinity chromatography on immobilized anhydrotrypsin: general utility for selective isolation of C-terminal peptides from protease digests of proteins. AB - Recently we have succeeded in the efficient isolation of the C-terminal peptides from tryptic digests of the tail sheath protein (with C-terminal Gly) and the tube protein (with C-terminal Glu) of bacteriophage T4, by taking advantage of a unique property of immobilized anhydrotrypsin, that is, a strong specific affinity for peptides containing Arg or Lys residues at their C-termini. In this study, the utility of affinity chromatography on immobilized anhydrotrypsin was further demonstrated in the cases of Streptomyces subtilisin inhibitor (as a reduced and S-carboxymethylated form, with C-terminal Phe) and alpha 1 antitrypsin (with C-terminal Lys). By subjecting a tryptic digest of the former protein and a chymotryptic digest of the latter protein to the affinity chromatography, the C-terminal peptides were specifically recovered in the breakthrough fraction and in the adsorbed fraction, respectively. It was further shown that immobilized anhydrotrypsin can also adsorb peptides with C-terminal S aminoethyl-Cys residues and exerts adsorptive ability even toward the peptides in solution containing urea at a high concentration if appropriate precautions are taken. These findings suggest the general utility of this simple method for C terminal peptide isolation, which is extremely helpful for studies to confirm amino acid sequences deduced from nucleotide sequences of the cDNA (or genomic DNA) of proteins. PMID- 3329197 TI - Strategies and mechanisms for the control of transcriptional initiation of mammalian protein-coding genes. PMID- 3329198 TI - Preliminary characterization of maturation-promoting factor from yeast Saccharomyces cerevisiae. AB - It has been known for some time that maturation-promoting factor (MPF) appears in a wide variety of eukaryotic cells at M phase and exerts equal M-phase-promoting activity in both meiotic cells and mitotic cells in a non-specific manner. MPF was extracted from cdc20 mutant cells of the yeast Saccharomyces cerevisiae synchronized at M phase by incubation at the restrictive temperature. When injected into immature oocytes of Xenopus laevis, yeast MPF caused meiosis reinitiation in a dose-dependent manner and even in the presence of cycloheximide. Yeast MPF exerted its activity in starfish oocytes as well. MPF activity was obtained only from cells in M phase and not from G1, S or G2 phase cells, indicating cyclical changes during the yeast mitotic cell cycle. Preliminary characterization of yeast MPF revealed that its activity was associated with a heat-labile protein having a sedimentation coefficient value of 6 S. In contrast to the current assumption that MPF is a Ca-sensitive phosphoprotein stabilized by phosphorylated small molecules, such as ATP and Na beta-glycerophosphate, the present study revealed that yeast MPF was still active even after treatment with either Ca2+ or alkaline phosphatase. Furthermore, it was found that yeast MPF and these phosphorylated small molecules were complementary in inducing reinitiation of meiosis, since the meiosis-reinitiating activity was detected only when both were present simultaneously and almost undetectable when either of them was present alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3329199 TI - Organization of the boar spermatozoan plasma membrane: evidence for separate domains (subdomains) of integral membrane proteins in the plasma membrane overlying the principal segment of the acrosome. AB - Indirect immunofluorescence microscopy and freeze-fracture have been used to identify overlapping subdomains at the peripheral rim of the sperm-head plasma membrane (PM) and the margin of the outer acrosomal membrane (OAM) comprising the principal segment of the acrosome of the boar spermatozoon. An array of ridge like structures (spaced 12-16 nm centre-to-centre), originally observed on the OAM by Aguas & Pinto da Silva, lies just beneath an area of the PM that is sparsely populated with large intramembranous particles compared to that of other regions of the head PM. This region has a high specificity for the lectin arachis hypogaea (peanut agglutinin). We suggest that the OAM at the rim of the sperm head may be rich in acidic phospholipids and that the close apposition of this membrane with a region of the PM relatively poor in integral membrane proteins may provide sites for initiating the acrosome reaction. PMID- 3329200 TI - Dairy animal welfare: current and needed research. AB - Of 25 milestones in dairy animal welfare, 10 were linked to laws and regulations, 9 to research, education, and development, 4 to books and publications, and 2 to human error (accidents). Animal rightists have attacked the dairy industry because of farm conditions, bovine somatotropin, overproduction of milk, dairy lobbies, and advertising of milk products. Evidence from Europe suggests that animal welfare has been largely promoted as a sociopolitical issue by nonagriculturalists. Codes, guidelines, and recommendations are well-established for northern Europe. The American Veterinary Medical Association Animal Welfare Committee has prepared the pamphlet on food animal welfare and addressed specific bovine welfare issues in its guide for veal calf care and production. From 1978 to 1986, only four US experiment station projects were concerned with dairy animal welfare. Needed research includes studying learned helplessness; analysis and economics of alternative husbandry systems for veal calves (and cows) freestall design and surfaces; and shade, cooling, and misting of mangers and holding pens prior to entering the parlor. Alert caretakers are encouraged to read behavior signals of cattle. Increased standing of cattle is often taken now as a sign of discomfort or discontent in studies of cow and calf confinement. Criteria that should be considered in assessing welfare or well-being are behavior, health, musculoskeletal soundness, productivity, physiological and biochemical characteristics, and reproduction. PMID- 3329201 TI - Immune function: relationship of nutrition and disease control. Vitamin A and beta-carotene on host defense. AB - Even though the protective role played by vitamin A and beta-carotene against numerous diseases has been clearly demonstrated, the exact mechanism by which they afford this protection is not completely understood. Impairment of the animal's immune system resulting from the vitamin deficiency may account for increased susceptibility to infection. This article attempts to draw from available information on the effects of vitamin A and beta-carotene on specific and nonspecific host defense mechanisms as they relate to disease. PMID- 3329202 TI - [An orbitocranial foreign body. Diagnostic reflections]. AB - The authors demonstrate how a delay in diagnosis, in the case of an orbito cranial foreign body, serves to underscore importance of CT in even minor, orbito facial injuries, when there is some suspicion of intracranial penetration. This examination, which should be requested as soon as possible in such cases, usually permits detection of the intracranial foreign body. However, if the image is much clearer than those of conventional X-rays, it can in certain cases, remain a matter of subtle interpretation, particularly in cases of less dense materials such as wood. PMID- 3329204 TI - [The Octopus G1 program. Description and use]. AB - The Octopus global analysis Program G1 was developed as a glaucoma program. It is the combination in a single program of: examination procedures, visual field assessment methods. The whole examination is carried out in three phases: the first phase measures 59 test locations in the central 30 degrees field. All locations are measured with the normal strategy. The local threshold is precisely determined to +/- 1 dB by the proven bracketing method. At the end of the first phase, the system automatically calculates the key values (visual field indices) for mean defect and loss variance. the second phase, which retests the same central field, starts from the threshold values measured during phase one. The additional indices corrected loss variance and short term fluctuation, are calculated. in the last phase 14 selected peripheral points between 30 and 60 degrees excentricity with particular emphasis on the superior and inferior nasal step are determined in a qualitative test. Visual field changes can be detected and categorized in three major groups: (Flammer and coll., 1985). 1. local defects or scotomas in varying depths and sizes. 2. diffused depression of the whole field. 3. Increased short-term. The original index called Corrected Loss Variance could determine an early defect before the existence of a light scotoma. Particularly, an increased Corrected Loss Variance indicates that the deviations are due to real scotomas and not just to scattering effects. The therapeutic decision could be more rational. PMID- 3329203 TI - [The eye and chronic inflammatory diseases of the intestines. Immunopathological and genetic aspects. Apropos of 3 cases]. AB - This study tried to approximate the mechanisms of ocular changes in Crohn's disease and ulcerative colitis. First, we reported a series of three patients with ocular complications and chronic inflammatory bowel disease. In all cases, we reported the association of ocular disorders with: various infections: intestinal, extra-intestinal complications, immunological troubles, genetic background: HLA B 27. Second, we reviewed the literature concerning ocular changes in ulcerative colitis and Crohn's disease. Recent immunological developments are studied, regarding: genetic aspects, allergic manifestations. immune complexes and role of IgA antibodies. Practically, uveitis, retinal inflammation or vasculitis can be associated with Crohn's disease and ulcerative colitis. Immunological studies of these patients will allow a better understanding of the mechanisms of the ocular lesions, which remain is complex, multiple and non specific. PMID- 3329205 TI - Recent advances in organ microcirculation research. AB - This review article dealt with progress in the research of gastroenterological organ microcirculation in Japan. It must be emphasized that this remarkable progress particularly in intravital microcirculatory observations at organ level is attributable to great improvement of microscopic devices combined with computerized system, development of new techniques for measuring microcirculatory blood flow and pioneering of a variety of fluorescent and isotope-labelled tracers. Little attention has been directed toward the fact that microvascular manifestations are perhaps the earliest signs of "cells and tissues" dysfunction in disease processes. The microvasculature undergoes a substantial remodeling not only in vascular wall structures, but also in network characteristics themselves especially in chronic disease. Those microvascular alterations in an organ system, which primarily originate in adaptations to the microenvironmental changes, would lead to the chronicity and self-perpetuation of disease. As has been noted in the IVth World Congress for Microcirculation organized by the Japanese Society for Microcirculation, which was held in Tokyo, July 26-30, 1987, further progress has been made in the research of organ microcirculation in the gastroenterological and other fields. It is the cornerstone for better understanding of the pathogenesis of organ diseases to clarify the earliest alterations in the microvasculature of an organ system from a combined aspect of microhemo- and microlymphocirculation using the newly developed techniques for microcirculation study. PMID- 3329206 TI - Antithrombotic and vasodilating effects of OP-41483, a prostacyclin derivative. AB - Anti-platelet and vasodilating actions of OP-41483, a derivative of prostacyclin, were studied experimentally and clinically. The ADP-induced human platelet aggregation was significantly inhibited in vitro, the rate being 59% with a dose of 3 micrograms/ml, 75% with 6 micrograms/ml and over 90% with 18 micrograms/ml or more. A significant reduction in deposition of platelet and mural thrombi on the chemically injured luminal surface of the canine femoral vein was observed by treatment with topical administration of the solution (10 micrograms/ml) and/or intravenous infusion (10 ng/kg/min). The blood flow rate of the normal canine femoral artery and the anterior or posterior tibial artery of patients with peripheral arterial occlusive disease at the ankle was moderately increased in cases of intravenous infusion of the compound at a rate of 10 ng/kg/min. PMID- 3329208 TI - [Study on mechanism and prevention of systematic complications during dental procedures]. PMID- 3329207 TI - The effectiveness of ketanserin in patients with primary Raynaud's phenomenon. A randomized, double blind, placebo controlled study. AB - In 41 patients with Primary Raynaud's Phenomenon (PRP) the effectiveness of the serotonin receptor blocker ketanserin has been studied in a double blind cross over study. Subjective assessments included: frequency and duration of the attacks (both per se and combined to a severity score), cold sensation, numbness, paresthesia, pain, cold water and cold weather provocation and the appearance of spontaneous attacks. The objective measurements comprised Digital Skin Temperature (DST), Digital systolic Blood Pressure (DBP) and Doppler Spectral Analysis (DOSA) of the radial and ulnar arteries. All measurements were performed both at room temperature and after instant cold provocation. The severity score, the occurrence of numbness and paresthesia and cold weather provocation improved significantly on ketanserin treatment. All objective measurements with the exception of the end-diastolic blood flow velocity of DOSA did not show significant improvements. Neither blood chemistry nor systemic blood pressure showed any significant change during ketanserin treatment. However, in the 6 (15%) patients with hypertension both systolic and diastolic blood pressure normalized. Although in objective measurements hardly any significant effects of ketanserin could be demonstrated, the results of the study suggest that orally administered ketanserin is effective for minimizing subjective complaints in patients with PRP. Ketanserin did not show any side effects. PMID- 3329209 TI - [Studies on Ni-Ti alloys for dental casting. Part 2: Improvement of corrosion resistance of Ni-Ti-Cu alloys by added elements]. PMID- 3329210 TI - A dentist in jeopardy. PMID- 3329211 TI - The effect of Eikenella corrodens endotoxin on periapical bone. PMID- 3329212 TI - Cloning and expression in Escherichia coli of Proteus vulgaris genes for 16S ribosomal RNA. AB - In contrast to the established systems of plasmid-coded homologous ribosomal DNA (rDNA) cistrons in Escherichia coli little is known about the fate of heterologous rRNA. In order to study expression of foreign rDNA, rRNA cistrons from Proteus vulgaris were cloned in phage vector Charon 35, subcloned in pBR322 and transformed in E. coli. The inserts of two clones (pPM2 and pPM14) were characterized by restriction analysis and Southern hybridization. Each of them harboured a complete rrn cistron. The location of rRNA genes of clone pPM2 was also verified by R-loop analysis. The 5' flanking region of the 16S rRNA of pPM2 was sequenced and compared to the E. coli counterparts. High-level homologies exist in the functional parts of this region, e.g. promoters, box A and RNAase III recognition site. The copy number of pPM2 and pPM14 was estimated to be 8 and 10, respectively. Clones showed a markedly reduced growth rate (generation time about 57 to 70 min) as compared to the non-transformed cells (generation time 40 min). rDNA cistrons of P. vulgaris were properly expressed and the transcripts are processed as demonstrated by the presence of 16S rRNA from P. vulgaris in both ribosomes and 30S ribosomal subunits isolated from the transformed E. coli cells. The fraction of heterologous rRNA in ribosomes was about 25%. PMID- 3329213 TI - An unmodified form of the ColE2 lysis protein, an envelope lipoprotein, retains reduced ability to promote colicin E2 release and lysis of producing cells. AB - Site-directed mutagenesis was used to replace the codon for the N-terminal cysteine residue of pColE2-P9-encoded mature lysis protein (CelB) by an arginine codon. In contrast to the wild-type CelB protein, the product of the mutated gene, which has an altered signal peptidase cleavage site, was neither processed nor acylated. However, the mutant protein retained sufficient residual activity to cause partial, Mg2+-suppressible lysis and could activate envelope phospholipase A1-A2 and promote colicin release, albeit with reduced efficiency compared to the wild-type protein. We propose that the uncleaved signal peptide of the mutant protein acts as the functional equivalent of the fatty acyl groups normally linked to the N-terminal cysteine residue of the wild-type protein, thereby anchoring the protein in the cell envelope where it exerts its various effects. PMID- 3329215 TI - Genetic analysis of conjugational recombination in Escherichia coli K12 strains deficient in RecBCD enzyme. AB - Conjugational recombination in Escherichia coli was investigated by comparing the effects of recN, recO, ruv and lexA mutations on the formation of recombinants in crosses with strains lacking RecBCD enzyme. The results presented reveal that recN and ruv mutations do not abolish residual recombination in a recB mutant, and have only a rather modest effect on recombination in recBC sbcA strains; in these respects they are quite different from recF, recJ and recO mutations. The differences between these two groups of genes are discussed in relation to the molecular exchanges needed to produce viable recombinants. PMID- 3329214 TI - Proteolysis of hexokinase PII is not the triggering signal of carbon catabolite derepression in Saccharomyces cerevisiae. AB - The role of hexokinase PII in mediating carbon catabolite derepression in yeast has been examined. Hexokinase isoenzyme PII (EC 2.7.1.1) was partially degraded when protease inhibitors were omitted from the buffer used for preparation of cell-free extracts. The hexokinase PII inactivation induced by D-xylose was correlated with derepression of maltase (EC 3.2.1.20) in the wild-type strain Saccharomyces cerevisiae G-517 and in D.308.3, a strain that contains the cloned hexokinase PII gene on a multicopy plasmid. This inactivation was not correlated with the loss of hexokinase PII protein as assayed by immunoblotting. We conclude that during the derepression process there is no release of proteolytic peptides from hexokinase PII. PMID- 3329216 TI - Qualitative evidence for expression of Klebsiella pneumoniae nif in Pseudomonas putida. AB - Pseudomonas putida MT20-3 carrying the Klebsiella pneumoniae nif plasmids pRD1 or pMF250 showed highly O2-sensitive aerobic acetylene reduction on low-N pyruvate or glucose agar. This finding confirms unequivocally that K. pneumoniae nif can be expressed in an obligate aerobe. PMID- 3329217 TI - Binding and cytotoxic effects of Clostridium botulinum type A, C1 and E toxins in primary neuron cultures from foetal mouse brains. AB - Binding of purified Clostridium botulinum type A, C1 and E toxins to cultured cells was studied by an immunocytochemical method. Type A and C1 toxins bound strongly to neuron cultures prepared from brains of foetal mice, but binding of type E toxin was weak. None of the toxin types bound to the feeder layer, composed of non-neuronal cells. The heavy-chain component of the type C1 toxin bound to neurons, but the light chain component did not. Type C1 toxin also bound only to cell lines of neuronal origin. When type C1 toxin [final concentration 4 x 10(2) LD50 (10 ng) per well] was added to primary neuron cultures in 96-well plates, degeneration of neuronal processes and rounding of neuronal somas were observed, but type A and E toxins did not produce such changes. The binding and cytotoxic activities of type C1 toxin were blocked by heat treatment (80 degrees C for 30 min) or by preincubation of the toxin with polyclonal anti-C1 IgG and some of the monoclonal antibodies which neutralized the toxin activity in mice. In the neuronal processes treated with C1 toxin, many degenerated mitochondria, membranous dense bodies and vesicles were observed by electron microscopy; these ultrastructural changes were similar to those of Wallerian degeneration in vivo. PMID- 3329218 TI - A case of aspergillosis of the maxillary sinus. PMID- 3329220 TI - Earlier orthodontic intervention: a view from prehistory. PMID- 3329219 TI - A preliminary report on bone transplantation. 1. An immunohistochemical study on the distribution and proportions of lymphocyte subsets in lymphoid organs of normal rats. PMID- 3329221 TI - Hine sight (Dr. Horace Wells). PMID- 3329222 TI - Child abuse: detecting and reporting. PMID- 3329224 TI - Spontaneous rupture of a splenic vascular malformation. A report of three cases and review of the literature. PMID- 3329223 TI - [Non-invasive assessment of the peak pressure gradient between the aorta and pulmonary artery in patent ductus arteriosus]. AB - The validity of continuous wave Doppler ultrasound estimation of the peak pressure gradient between the aorta (Ao) and pulmonary artery (PA) in patients with patent ductus arteriosus (PDA) was evaluated. Ten patients, all without other anomalies, underwent cardiac catheterization and cine-angiography, and the peak pressure gradient between the Ao and PA (dP(C)) was measured during catheterization. In all cases the mean PA pressure was less than 35 mmHg. According to the angiographic findings, the patients were categorized as Group A, consisting of seven patients whose features of the ductus were wedge- or tube like in configuration; Group B, consisting of two patients whose features were termed "orifice-like" stenosis including one with abrupt narrowing on the PA side of the ductus and the other with a short segmental ductus. Group C consisted of one patient who had a long curved segmental ductus. The maximum velocity of ductus flow was measured by continuous wave Doppler ultrasonography, and the estimated peak pressure gradient between the Ao and PA by Doppler (dP(D] was calculated using the simplified Bernoulli equation (dP = 4V2). In group A, dP(D) was overestimated compared to dP(C) in all patients by 19 to 51 mmHg (mean 34 mmHg). However, in group B, the difference between dP(D) and dP(C) was small, 5 mmHg and 7 mmHg, respectively. In group C, dP(D) was underestimated as opposed to dP(C). Thus, in the limited cases, the simplified Bernoulli equation could be used in estimating the peak pressure gradient between the Ao and PA. However, this equation leads to overestimation in many cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3329225 TI - A simple method for the detection of Chlamydia trachomatis infections in general practice. AB - Chlamydial infection is an important cause of genital tract disease in women and is often silent. Collection, storage and transportation of specimens required for culture pose problems which have made studies difficult and diagnosis impractical outside hospitals or sexually transmitted disease clinics.The direct monoclonal antibody test (MicroTrak, Syva) for detecting chlamydiae is comparable with the traditional culture method in sensitivity and specificity. The test requires only the preparation of a smear on a slide, making it convenient for use in general practice. The feasibility of using this procedure in an inner city practice was demonstrated in tests on 188 women who required pelvic examination. Of 169 women from whom valid specimens were obtained 18 (10.7%) were found to have a chlamydial infection. Only three of the infected women were asymptomatic and the organisms were associated particularly with dysuria. The value of the test in comparison with other procedures currently available for detecting chlamydiae is emphasized. PMID- 3329226 TI - No laughing matter. PMID- 3329227 TI - Immunological studies in children with type I diabetes mellitus and their healthy relatives: in vitro antigen stimulated IgM production, T-cell subsets and islet cell antibodies. AB - Several defects in immunoregulation have been described in patients with insulin dependent diabetes mellitus (IDDM). We have looked at immunoregulatory T-cell subsets autoantibodies and in vitro IgM production in IDDM patients and their healthy first degree relatives. The proportions of total T-cells (OKT11+), helper/inducer (OKT4+), suppressor/cytotoxic T-cells (OKT8+) and OKT4/OKT8 ratio were normal in 8 patients as well as in their 26 family members and in 40 age matched controls. Anti islet-cell antibodies (ICA) were found in sera of 6 out of 17 patients (35%) in 1 out of 62 (1.6%) family members and in none of the age matched healthy controls. A significant increase of in vitro IgM production was found in 8 patients (130 +/- 10 PFC/10(6) cultured cells, mean +/- S.E.) as compared to 21 healthy controls (57 +/- 5.0) (p less than 0.01). In vitro IgM production by B-cells of 22 family members was also increased compared to controls (83 +/- 8.0) (p greater than 0.05). This increased antibody production is characteristic for clinical states associated with impaired immunoregulation, and reflects perturbation of immunoregulatory mechanisms in IDDM. PMID- 3329228 TI - A component of Mycobacterium leprae as immunomodulating agent for immune deficient cells of leprosy patients. AB - The delipidified component of the insoluble portion which presumably is the cell wall of Mycobacterium leprae (DCW) was able to induce lymphocyte proliferation in the leucocyte culture from the peripheral blood of lepromatous leprosy patients. Normally these cells show no lymphocyte proliferation in response to M. leprae or their sonicated extract. The delipidified component (DCW) appears to be proteinaceous and able to induce antibodies in rabbit. The DCW has affinity to the sera from lepromatous leprosy patients but not sera from normal healthy individuals or tuberculoid leprosy patients. The ability to induce lymphocyte proliferation is blocked by agglutination of DCW with patient sera, heat treatment of DCW or protease treatment of the component. Along with lymphocyte proliferation, DCW also induces ability in the macrophages to render phagocytosed M. leprae non viable. Thus it is proposed that DCW of M. leprae could be a potent immunomodulator for immunedeficient cells of leprosy patients. The efficacy of DCW as a probable immunoprotector for M. leprae infection in mice has already been demonstrated earlier. PMID- 3329229 TI - Cardiac glycosides in traditional Chinese medicine. PMID- 3329231 TI - The anesthetic management of allo-pancreatic transplantation. PMID- 3329230 TI - Reinnervation of free transferred muscle by nerve suture and nerve implantation in combination--an experimental study. PMID- 3329232 TI - [Intussusception in adults--report of nine cases]. PMID- 3329233 TI - [A study of bile enterotoxin in cholelithiasis]. PMID- 3329234 TI - Ultrastructure of the human pituitary adenoma. PMID- 3329235 TI - The efficacy of nonsurgical periodontal therapy by ultrasonic scaling and root planning. I. Clinical evaluation of probing pocket depth. PMID- 3329236 TI - The changing role of microbiology in a changing global society. PMID- 3329237 TI - [Stress distribution on different marginal preparations of cast post-core--a finite element stress analysis]. PMID- 3329238 TI - [Myelolipoma of the adrenal gland--a case report]. PMID- 3329239 TI - Nonparasitic true splenic cyst: a case report of lymphangioma of the spleen. PMID- 3329240 TI - [Assessment of bile regurgitation in obstructive jaundice by an intrahepatic choledochal injection method]. PMID- 3329241 TI - A study of the relationship between beta-glucuronidase and cholelithiasis. II: Activity of E. coli and their OK antigen serotypes. PMID- 3329243 TI - [Cloning and expression in Escherichia coli of Vibrio parahaemolyticus thermostable direct hemolysin and thermolabile hemolysin genes]. PMID- 3329242 TI - [New antimicrobial agent series XXVIII: cefuzonam]. PMID- 3329244 TI - [Chemotherapy of compromised hosts]. PMID- 3329245 TI - [The problems of chemotherapy from a bacteriological point of view: recent alternation of bacterial resistance. B. Gram negative bacilli]. PMID- 3329246 TI - [Antitumor effects of a novel immunomodulator, holding many bioactivities in common with endotoxins, derived from Mycobacterium bovis BCG]. PMID- 3329248 TI - [Trends in research in developing new type of vaccines--aiming at efficacy and safety. Viral hepatitis B vaccine]. PMID- 3329247 TI - [New technology of vaccine production--international prospect of the development- subunit vaccine obtained by genetic engineering. a. Application of genetic engineering using Saccharomyces cerevisiae]. PMID- 3329249 TI - [Mechanism of the oncogenesis of Herpesviridae]. PMID- 3329250 TI - [From clinical tests to etiology: analysis of clinical features]. PMID- 3329251 TI - [Clinical application of energy subtraction imaging using digital radiography for excretory urography in infants]. PMID- 3329252 TI - [Diagnosis of thyroid nodules--a comparative study of soft-tissue radiography, ultrasonography and aspiration biopsy cytology]. PMID- 3329253 TI - [A case of solar urticaria--a view of the mechanism of inhibition spectrum]. PMID- 3329254 TI - The first trimester prenatal diagnosis of Pompe's disease at risk. PMID- 3329255 TI - [Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation]. PMID- 3329256 TI - [Rapid diagnosis of pulmonary tuberculosis by detection of tuberculostearic acid with gas chromatography/mass spectrometry]. PMID- 3329257 TI - [Errors and complications of endovascular occlusion of patent ductus arteriosus]. PMID- 3329258 TI - [Arrest of hemorrhage from the ascending aorta during operations under artificial circulation]. PMID- 3329259 TI - [Successful surgical treatment of rupture of an aneurysm of the abdominal aorta into the inferior vena cava]. PMID- 3329260 TI - [Artificial arteriovenous fistula in the treatment of chronic arterial insufficiency of the extremities (review of the literature)]. PMID- 3329261 TI - [Surgical tactics in complicated forms of cancer of the colon (review of the literature)]. PMID- 3329262 TI - [Calendar of anniversary dates in the history of surgery 1988]. PMID- 3329263 TI - [Dopplerometry in determining the optimal level of amputation of the leg]. PMID- 3329265 TI - Assessment of acupuncture in the prevention of sudden death from coronary heart disease. PMID- 3329264 TI - [Extirpation of the esophagus with simultaneous gastroplasty]. PMID- 3329266 TI - Xu ZhiCai, a famous physician of the Northern Dynasty. PMID- 3329267 TI - The earliest officially published pharmacopoeia in the world. PMID- 3329268 TI - The effect of neuropeptides on cellular proliferation. PMID- 3329270 TI - Neuropeptides--the present state of research work. PMID- 3329271 TI - Neuropeptides and the cerebral bioelectric activity. PMID- 3329269 TI - Vasopressin and oxytocin release into the cerebrospinal fluid. PMID- 3329272 TI - Circulatory and metabolic effects of neuropeptides in stomach and intestine. PMID- 3329273 TI - The role of opioid peptides in the control of secretion of pituitary hormones. PMID- 3329274 TI - [Salt and arterial hypertension]. PMID- 3329275 TI - [Diagnosis and treatment of idiopathic hemochromatosis]. PMID- 3329276 TI - [Extra-hospital pneumonia caused by Escherichia coli. Review of 15 cases]. PMID- 3329278 TI - [Idiopathic intracranial hypertension. Diagnosis and treatment]. PMID- 3329277 TI - [Postmortem study of renal lesions in 4 recipients of liver transplants treated with cyclosporin A]. PMID- 3329279 TI - [Calcium antagonists in cerebral resuscitation]. PMID- 3329280 TI - [Anesthetic management for surgical patients with paraquat intoxication--case report and literature review]. PMID- 3329281 TI - Nucleotide sequence and transcriptional startpoint of the glpT gene of Escherichia coli: extensive sequence homology of the glycerol-3-phosphate transport protein with components of the hexose-6-phosphate transport system. AB - The nucleotide sequences of the glpT gene of Escherichia coli and its regulatory region have been elucidated and the primary structure of the glycerol-3-phosphate transport protein deduced. Extensive amino acid sequence homology was found with two other cytoplasmic membrane proteins: the functionally related hexose-6 phosphate transport protein, and the UHPC protein involved in regulating hexose-6 phosphate uptake. Although no significant amino acid sequence homology was found with other transport proteins, such as the arabinose, citrate, glucose, melibiose, lactose or xylose transporters, all of these proteins share a common secondary structure arrangement with the GLP T protein as they apparently contain twelve membrane-spanning alpha-helical segments. The promoter for glpT was located by transcript mapping and shown to overlap a site to which catabolite activator protein binds in vitro. These findings indicate how catabolite repression may be mediated but do not explain its physiological significance in glycerol metabolism. PMID- 3329282 TI - Effects of deletions in the spacer region of the rrnB operon on the transcription of the large ribosomal RNAs from Escherichia coli. AB - A series of deletions was constructed within the spacer region of the genes for the 16S and 23S RNA on plasmids bearing the rrnB operon. The accumulation and synthesis rates for the 16S and 23S RNAs were determined from normal growing cells and maxicells after transformation with the mutated plasmids. A marked difference in the transcription efficiency of the plasmid-encoded ribosomal 16S and 23S RNAs was observed with cells carrying plasmids, where a sequence motif analogous to the antitermination recognition sequence (Box A) had been deleted. The overall synthesis rate of ribosomal RNAs of such cells was not altered, however, indicating that the difference in transcription rates from the plasmid genes is compensated by altered transcription rates of the corresponding chromosomal genes. In addition, the accumulation of various tRNA species encoded on rRNA operons and non rRNA operons was quantitated and compared. From these results we infer that the regulation of ribosomal RNA transcription does not only occur at the promoter sites but sequence regions possibly involved in antitermination within the operon are crucial for a coordinated synthesis of all ribosomal RNAs. PMID- 3329283 TI - [Cell wall permeability and export of proteins into the culture broth of Saccharomyces cerevisiae]. AB - The upper limit of Saccharomyces cerevisiae cell wall permeability is such that only molecules with a mass not greater than 2-3 kDa can pass across the cell wall. However, proteins with a much higher molecular mass are exported into the cultural broth when the organism is cultivated in a liquid medium with peptone. Under certain conditions, exogenous proteins interact with the cytoplasmic membrane. These as well as some other findings imply that the cell wall may have microplots with an anomalous permeability, via which the regulated exchange of macromolecules is realized between the intracellular and outer media. PMID- 3329285 TI - [Role of membrane damage in the inactivation of yeast cells by visible light]. PMID- 3329286 TI - [Relation of fluctuations in the physiological traits of a continuous Saccharomyces cerevisiae culture to the cell division cycle]. AB - Such physiological characteristics of a continuous Saccharomyces cerevisiae culture as the rate of O2 uptake and CO2 evolution, the rate at which the medium was acidified, were found to vary. When the flow rate was increased from 0.05 to 0.1 h-1, the period of variations also rose (from 3 to 33 h) and two maxima were detected in the quantity of budding cells within one 33-h period of the variations. These findings indicate that the variations do not depend on changes in the physiology of the cell in the course of its division cycle. PMID- 3329284 TI - [Importance of Bdellovibrio in regulating microbial cenoses and self-purification processes in domestic sewage]. AB - The bacterial parasite Bdellovibrio was directly proved to be involved in the regulation of microbial cenoses and in the self-purification of domestic waste waters. The incidence of heterotrophs, Gram-negative bacteria, E. coli and Bdellovibrio was followed up in dynamics in the microecological system of waste waters for ten days. In control experiments, bdellovibrions were removed using pteridine as a vibriostatic agent. In the absence of bdellovibrions, the cell number of the studied microorganisms did not increase after reaching a stationary level. In the control, the total incidence of heterotrophs decreased 1355 times, that of Gram-negative bacteria fell down 527 times, and that of E. coli cells dropped 3419 times due to the interaction between the host bacteria and Bdellovibrio. The variations in the number of interacting cells were characteristic of a two-component parasite-host system. PMID- 3329287 TI - [Effectiveness of the immunoenzyme method in the diagnosis of opisthorchiasis]. PMID- 3329288 TI - [Acid phosphatase activity of circulating leukocytes in mice in experimental malaria]. PMID- 3329289 TI - [Achievements in the control of the chief parasitic diseases in the Ukrainian SSR (1917-1987)]. PMID- 3329290 TI - [The role of anthropogenic factors in the formation of foci of diphyllobothriasis in reservoirs]. PMID- 3329291 TI - [Experience in creating a system of scientific information support for research work and branch programs in the field of parasitic diseases]. PMID- 3329292 TI - [Trigeminal neuralgia due to ill-fitting dentures]. PMID- 3329293 TI - [Immunohistological aspects of a case of radicular cyst complicated by reparative granuloma]. PMID- 3329295 TI - [The glorious jubilee of the land of the Soviets]. PMID- 3329294 TI - Surgical-stress-related suppression of natural killer cell activity: a possible role in tumor metastasis. PMID- 3329296 TI - [Corticofugal effects on the neuronal activity of the vestibular nuclei in the cat]. AB - Neuronal responses to stimulation of vestibular (V1), motor and orbital brain cortex were recorded extracellularly in lateral and medial vestibular nuclei of bulbar complex in experiments carried on nonanesthetized immobilized cats. Both phasic and (more often) tonic responses mainly of inhibitory type were observed. In morphological experiments the horseradish peroxidase was injected into the above nuclei. Marked neurons were found in the anterior supra- and ectosylvian brain gyri, in the region of cruciform sulcus and orbital cerebral cortex. The obtained data are discussed in the aspect of corticovestibular interaction. PMID- 3329297 TI - [Afferent connections of the dorsal sections of the pars magnocellularis in the red nucleus of the cat]. AB - Location of retrogradely labelled neurons in various structures of the central nervous system was studied by microiontophoretic injection of horseradish peroxidase into dorsal sections of the magnocellular part of the cat red nucleus. Projections were revealed from some hypothalamic nuclei, centrum medianum, as well as from nucleus parafascicularis and subthalamic nucleus; from zone incerta, field of Forel, nucleus medialis habenulae; from reticular formation of the pons, medulla oblongata and midbrain, central gray matter, colliculus superior, nucleus interstitialis Cajal; from contralateral red nucleus, nucleus fastigii and facial nucleus; from nucleus vestibularis lateralis (pars dorsalis) and nucleus vestibularis medialis as well as from ventral horn of the spinal cord cervical segments. Connections between substantia nigra and the red nucleus have been studied more accurately. Bilateral trajectories of retrogradely labelled fibre systems are described. PMID- 3329298 TI - [Pineal metastasis--a case report and a review of literature]. AB - This is a report of a rare case of pineal metastasis from gastric adenocarcinoma. A 75-year-old male with a previous medical history of subtotal gastrectomy for cancer of the cardia was diagnosed as having hydrocephalus 6 months later. After undergoing a V-P shunt operation, he was transferred to Kyoto First Red Cross Hospital. The patient had neurological abnormalities: bilateral paralysis of upward eye movement, and bilateral sluggish reflex to light. Ten days later the patient suddenly fell into a coma due to intratumoral hemorrhage. The patient soon regained consciousness and received Cobalt-therapy. However he died two months later of pulmonary malfunction due to pulmonary metastasis. An autopsy revealed a pineal tumor metastasized from gastric adenocarcinoma. The tumor involved the body of the pineal gland, and was expanded having a sharply defined margin which extended to the posterior portion of the third ventricle and the bilateral basal ganglia. PMID- 3329299 TI - [A case of iatrogenic traumatic intracranial aneurysm]. AB - A case of traumatic aneurysm due to an arterial injury during removal of a tuberculum sellae meningioma is reported. A 43-year-old man had undergone craniotomy for removal of the tumor. It was very hard with many feeders from bilateral anterior cerebral arteries (ACA), so the resection between the left ACA and the tumor was difficult. A small artery was accidentally pulled out from the left ACA and bleeding occurred from the small artery in the artery. The ACA was trapped temporarily with two clips and was coated using Oxycell and Biobond. The bleeding was stopped by this procedure and the blood reflowed. This tumor was removed totally, but postoperative CT scan showed an enhancing small lesion in the anterior part of the left basal ganglia 10 days after operation. The angiograms performed next day revealed a fusiform aneurysm of the left proximal ACA near the anterior communicating artery. The skull was reopened to treat the aneurysm. The aneurysm arising from just a bleeding point in the previous operation was oval in shape without neck, so it was trapped by two small aneurysm clips and resected. The patient's condition was uneventful after the second operation. Pathological diagnosis of the aneurysm was confirmed a false aneurysm. Iatrogenic traumatic aneurysms caused by neurosurgical procedure has been reported in 29 cases. Eighteen cases showed bleeding from injured artery during surgery and a half of them showed rupture from the aneurysm within one month after operation. Such doubtful cases of traumatic aneurysm should be diagnosed by angiography and operated as early as possible. PMID- 3329300 TI - Automated measurements of cerebral atrophy in multiple sclerosis. AB - An automated method of measuring cerebral atrophy is introduced. Using this method we studied patients with multiple sclerosis and a control group showing premature cerebral atrophy in multiple sclerosis (P = 1,32 x 10(-8) for male and P = 3,6 x 10(-14) for female). There was only a weak correlation between cerebral atrophy and psychological deficits. Multivariate analysis did not show any significant correlation between cerebral atrophy, duration of disease, clinical manifestations and progression of disease. We conclude that our method to measure cerebral atrophy is more accurate and less time-consuming than the use of linear indices. It might be appropriate for further investigations in evaluating atrophic processes in cerebro-vascular, degenerative and exogen-toxic disease of brain. PMID- 3329301 TI - Long-term follow-up of children with magnetic resonance imaging and ultrasound after treatment of brain tumors. AB - This paper compares the results of MRI and US follow-up examinations of 46 children who had undergone surgery for brain tumors. The cases included 42 posterior fossa tumors, 3 supratentorial tumors and 1 upper cervical spinal cord tumor. US examination proved to be less specific and sensitive than MRI. However, when a "bone window" is available, US is, because of the ease of its application, better suited for frequent routine examinations. Long-term follow-up should, therefore, consist of frequent regular US examinations combined with yearly MRI examinations. PMID- 3329302 TI - Survey of clinical experience with nimodipine in patients with subarachnoid hemorrhage. AB - The present studies show that nimodipine prevents and/or improves permanent ischemic neurological deficits in patients with subarachnoid hemorrhage. This was particularly marked in four double-blind, placebo-controlled studies in which statistically significant reductions in mortality and morbidity as consequence of cerebral vasospasm were found. The drug has been shown to increase cerebral blood flow, to reduce vasoconstriction, although not to fully prevent angiographic vasospasm, and to improve central conduction time. Nimodipine did not increase the rate of rebleeding. Its administration during anesthesia does not result in management problems. In general, nimodipine was well tolerated. Side effects were recorded mainly in open studies using the intravenous formulation and consisted mainly of decreases in blood pressure and headaches. Transient increases in liver enzymes may be due to the organic solvent. Hence, all results indicate that patients with subarachnoid hemorrhage will benefit from preventive or therapeutic nimodipine treatment. PMID- 3329304 TI - [Gastric plication in upper intrathoracic mechanical esophagogastrostomy]. PMID- 3329303 TI - Sonography and computed tomography in the diagnosis of orbitocranial malformations and tumors. AB - Standardized sonography and CT scanning have distinct advantages and disadvantages in the evaluation of patients with orbital diseases. Echography provides an efficient screening examination in patients presenting with signs and symptoms of orbital pathology. It allows the detection, localization, measurement and in almost 80% differentiation of orbital lesions. High resolution CT scanning gives an excellent topographic display of masses in the orbit. In visualization of intracranial causes of orbital processes and demonstration of changes in the posterior third of the orbit, in the orbital bones and the periorbital sinuses it is superior to ultrasonography. PMID- 3329305 TI - [Current trends in the diagnosis of tumors of the bladder]. PMID- 3329306 TI - [Epidemiology of deep venous thrombosis and pulmonary embolism]. PMID- 3329307 TI - [Thrombolytic therapy in acute deep venous thrombosis of the lower limbs: selection, indications and limits]. PMID- 3329308 TI - The historical background and global importance of heartwater. AB - The first written record of what probably could have been heartwater originates from South Africa and dates back to 1838. Since then, the disease was described from almost all the African countries south of the Sahara as well as from Madagascar, Sao Tome, Reunion, Mauritius and a number of islands in the Caribbean. Most research on the disease, at least until recently, was conducted in South Africa. Progress in research was slow but a few outstanding findings are mentioned in this paper. Despite inadequate information on its actual economic impact on livestock production, it is generally accepted that heartwater is either the most or second most important tick-borne disease in Africa. Depending on the area, heartwater ranks either second or third amongst diseases such as East Coast fever, tsetse-transmitted trypanosomiasis, rinderpest and perhaps also schistosomiasis. Heartwater is a major obstacle with regard to the introduction of highly producing animals intended for the upgrading of local breeds. Furthermore, it remains a major threat to areas such as the American mainland, where potential vectors are present but where the disease does not occur. PMID- 3329309 TI - Heartwater. The development and life cycle of Cowdria ruminantium in the vertebrate host, ticks and cultured endothelial cells. AB - Various aspects of the development and life cycle of Cowdria ruminantium are discussed. C. ruminantium is transmitted transstadially by certain Amblyomma species. Apparently organisms initially develop in the gut epithelial cells of ticks and subsequent stages of C. ruminantium invade and develop in the salivary gland acini cells of the vector. Stages at which transmission to the final host are attained appear to be coordinated with the feeding cycle of the ticks and the vertebrate host is infected via salivary glands of the tick. In the vertebrate host, ticks and cultured endothelial cells, different morphological forms of C. ruminantium (electron-dense and reticulated forms) are found. Organisms enter cells through a process resembling phagocytosis and reticulated forms of the organisms appear to be the main vegetative stage. In the vertebrate host, organisms proliferate in vascular endothelial cells, neutrophils, macrophages and reticulo-endothelial cells. PMID- 3329310 TI - The present state of Cowdria ruminantium cultivation in cell lines. AB - Attempts were made to grow 4 isolates of Cowdria ruminantium in cell lines. Three of these isolates, viz. Ball 3, Welgevonden and Kwanyanga, could be cultivated in a calf endothelial cell line, but experiments with the Kumm isolate have so far failed. The successful in vitro cultivation of 2 isolates (Welgevonden and Kwanyanga), which are also pathogenic for mice, has great potential for future studies and these aspects are discussed in this review. PMID- 3329311 TI - Metabolism and genetics of chlamydias and rickettsias. AB - Chlamydial and rickettsial diseases pose a hazard to man and to domesticated and wild animals. The virulence mechanisms which aid the establishment of these obligate intracellular parasites in the eukaryotic host are still not within our grasp. Recent knowledge of the biochemical stratagem, the metabolic capabilities and the genetic diversity of these microbes illustrate fundamental differences in ecology and evolutionary divergence. The preferred site of intracellular residence determines the strategy for uptake, for nutrient assimilation and also for evasion of the host's immunological defenses. The Chlamydia, Rickettsia, and Coxiella are the most extensively studied of the genera. Whereas the Ehrlichia and Cowdria are poorly understood, they are also the most intriguing of the Rickettsiae. A number of antigenically and genetically distinct species are identified for the genera Chlamydia, Rickettsia, and Ehrlichia, whereas the Coxiella and Cowdria may not represent such a wide diversity. Recent information on the genetic heterogeneity of the chromosomal and plasmid DNAs of the strains of Coxiella suggest the diversity is greater than was originally envisioned. New information regarding the antigenic structure of Cowdria and their cellular tropisms suggests that they are closely related to the Ehrlichia. In this review we compare the metabolic capabilities and the genetic diversity of these different intracellular bacteria. PMID- 3329313 TI - Purification of Cowdria ruminantium by lectin cellular affinity chromatography. AB - This review covers the isolation of Cowdria ruminantium by lectin cellular affinity chromatography from different Amblyomma hebraeum sources. Cellular affinity chromatography has been reviewed with special attention being given to the application of this technique in the isolation of rickettsiae. PMID- 3329312 TI - Purification of Cowdria ruminantium by density gradient centrifugation. AB - The isolation of Cowdria ruminantium by differential and isopycnic density gradient centrifugation is reviewed with special reference to the suitability of Percoll as density gradient medium. Infected sheep brain, Amblyomma hebraeum nymphae and various mouse organs were used as starting material. By these methods, partially purified viable populations of the organism with distinctly different densities were obtained. The conclusions are based upon results of analyses of density fractions by inoculation into sheep or mice, protein determination, electron microscopy and enzyme-linked immunosorbent assay. Morphological differences were observed in the density fractions obtained from infected brain tissue and A. hebraeum. PMID- 3329314 TI - Purification of Cowdria ruminantium by immunoadsorbent affinity chromatography. AB - Immunoselective methods with special reference to immunoadsorbent affinity chromatography as a means for the isolation of Cowdria ruminantium are reviewed. Attention is given to the source of the organism, immunization, purification of antibodies, coupling of antibodies to insoluble matrixes and desorption procedures. PMID- 3329315 TI - Heartwater. An overview of the clinical signs, susceptibility and differential diagnoses of the disease in domestic ruminants. AB - Heartwater is a frequently fatal tick-borne disease of ruminants caused by Cowdria ruminantium. In domestic ruminants the incubation period varies considerably and depends on the route of infection, virulence of the isolate and amount of infective material administered. Adult cattle of all breeds appear to be equally susceptible to heartwater. It is generally accepted that calves up to the age of 3 weeks have a high degree of natural resistance which is not related to the immune status of the dam. Nervous symptoms are frequently seen in animals affected by the peracute and acute forms of heartwater and can easily be confused with similar signs caused by infectious conditions, toxic plants, acaricide and heavy metal poisonings. PMID- 3329317 TI - Heartwater in hosts other than domestic ruminants. AB - The importance of further research on the susceptibility of wild hosts to Cowdria ruminantium infection is discussed. The literature is surveyed and an attempt is made to divide the various species described into susceptible and refractory hosts. The reasons for the numerous apparently conflicting reports are considered and it is suggested that those making further inquiries in this field of work take these factors into account. PMID- 3329316 TI - Cowdria ruminantium infection in the mouse: a review. AB - The current knowledge of the pathogenicity, clinical signs and mortality of artificial infections by syringe inoculation of Cowdria ruminantium in laboratory and wild strains of mice is reviewed. It is concluded that a wide spectrum of pathogenicity for mice exists in stocks of the organism. PMID- 3329318 TI - Heartwater. The artificial transmission of Cowdria ruminantium in domestic ruminants and mice. AB - The artificial transmission of Cowdria ruminantium with infected blood, organ homogenates, peritoneal macrophages, tick stabilate and tissue culture cells is discussed. Organ homogenates prepared from the myocardium, spleen, kidneys and liver of diseased animals are commonly used to infect mice. The efficacy of organ homogenates as a source of C. ruminantium depends on factors such as the route of inoculation and the heartwater isolate used. Heartwater is artificially transmitted with infected tick stabilate, haemocytes, rectal ampules and hypodermal homogenates. The infectivity of saliva collected from Amblyomma hebraeum female ticks was very low compared to the ground-up suspensions prepared from the same group of ticks. PMID- 3329319 TI - The pathology of heartwater. III. A review. AB - The pathological changes in cattle, sheep, goats, mice and various game species infected with Cowdria ruminantium are summarized. Macroscopical lesions in most animals include effusion of body cavities, oedema of the lungs and lymph nodes and splenomegaly. Apart from the presence of heartwater organisms in most organs the histopathological lesions are not striking. The ultrastructural lesions in the lungs of sheep and goats infected with the Ba11 3 strain of heartwater, and mice infected with the Welgevonden strain, are discussed. Damage to capillary endothelial cells of the alveoli is limited and the mild cytopathic changes in parasitized cells indicate that the damage caused by the organisms is most probably not responsible for the increased vascular permeability associated with the disease. Pathological changes in domestic ruminants and game animals are briefly compared. PMID- 3329320 TI - The clinical pathology and pathophysiology of heartwater: a review. AB - This paper reviews the available literature on the clinical pathology and pathophysiology of heartwater and makes comparisons with unpublished results obtained from a recent study in experimentally-induced heartwater in calves. The pathophysiological changes seem to center on an increased capillary permeability the result of which is reflected most noticeably in cardiac and lung function. There is a marked drop in cardiac output in severe cases and some workers have recorded a severe drop in diastolic blood pressure in the advanced stage of the disease. Changes in lung function are variable, depending on the stage of the disease, and may change from a respiratory alkalosis in the early febrile stage to a respiratory acidosis in more advanced cases. The basic cause for the increased capillary permeability is not known. The main clinical pathological changes measured include a progressive anaemia, fluctuations in total and differential white cell count, of which an eosinopenia and a lymphocytosis are the most marked, increases in total bilirubin which coincide with darkening of plasma colour, and a drop in total serum proteins mostly shown in the albumin levels. PMID- 3329321 TI - The pathogenesis of heartwater. AB - Hypotheses on the pathogenesis of heartwater, which have been published so far, are briefly reviewed. Attempts were made at counteracting the effects of vaso active substances released by mast cells by treating mice infected with Cowdria ruminantium with antagonists to histamin and serotonin on one hand, and with mast cell stabilizers on the other, but were not successful. Preliminary findings suggest that a hypersensitive type of reaction, triggered by the release of pharmacologically active substances, may possibly be basic to the pathogenesis of heartwater. Complement, and the products of arachidonic acid metabolism, possibly play a role in the release of the vaso-active substances. PMID- 3329322 TI - The application of the indirect fluorescent antibody test in research on heartwater. AB - The preparation of the antigen, details of the reagents, the titration of the antispecies conjugates and the execution of the indirect fluorescent antibody test are described. The sensitivity and specificity of the test and its applicability to the detection of antibodies to Cowdria ruminantium are recorded. The test is both highly specific and sensitive and can be applied to a wide range of studies on heartwater, including epidemiology, determination of the C. ruminantium infection rate of Amblyomma ticks and the evaluation of immunization against heartwater. The test can also be used to detect antibodies to the heartwater agent in the sera of game. PMID- 3329323 TI - Heartwater serology: some problems with the interpretation of results. AB - Antibodies in the sera of domestic ruminants that have been infected with Ehrlichia bovis and other ehrlichial agents cross-react with the Kumm strain of Cowdria ruminantium used in the indirect fluorescent antibody test as antigen. These cross-reactions are also shown by the Elisa test in which the Ball 3 strain of the heartwater agent is used as antigen. PMID- 3329324 TI - Natural transmission of heartwater. AB - Heartwater has been transmitted experimentally by 12 Amblyomma species. Their importance depends on the extent of their distribution, adaptation to domestic stock and their efficacy as vectors. Except for one report of transovarial transmission, transmission is transstadial. Ticks may obtain the infection while feeding on reacting animals, subclinically infected hosts or perhaps on immune animals after reinfection. There is a marked increase in the infectivity of infected ticks during feeding but this decreases before and during moulting. The demonstration of Cowdria ruminantium in salivary glands of ticks suggests that transmission takes place via the saliva and that regurgitation from the gut may not be as important as previously thought. Transmission takes place on the 2nd day from the time infected nymphae were placed on the animals and on the 4th-day in the case of adult ticks. PMID- 3329325 TI - The tick vectors of Cowdria ruminantium (Ixodoidea, Ixodidae, genus Amblyomma) and their distribution. AB - Twelve species of Amblyomma are presently known to be capable of transmitting Cowdria ruminantium. Of these A. variegatum is the most important and widely distributed vector in Africa. It has also extended its range considerably outside this continent, eastward to the Yemen Arab Republic and to the islands of Madagascar, Reunion and Mauritius, and westward to the Cape Verde islands and to some of the West Indian islands. A. hebraeum is probably the only field vector in most parts of southern Africa. A 3rd species, A. lepidum, is known to have been involved in field outbreaks of heartwater in the Sudan. Two other species are also currently regarded as field vectors of Cowdria: A. astrion on the islands of Sao Tome and Principe, and A. pomposum in Angola. Another 5 African species (A. cohaerens, A. gemma, A. tholloni, A. sparsum and A. marmoreum) have proved to be capable of transmitting heartwater in the laboratory, as have 2 American species (A. maculatum and A. cajennense), but none of these ticks have been implicated in field outbreaks of the disease. PMID- 3329326 TI - The ecology of the African vectors of heartwater, with particular reference to Amblyomma hebraeum and Amblyomma variegatum. AB - The hosts, sites of attachment, life cycle, habitat requirements and seasonal abundance of Amblyomma astrion, Amblyomma cohaerens, Amblyomma gemma, Amblyomma hebraeum, Amblyomma lepidum, Amblyomma marmoreum, Amblyomma pomposum, Amblyomma sparsum, Amblyomma tholloni and Amblyomma variegatum, the 10 potential vectors of heartwater in Africa, are listed. Factors influencing the distribution and abundance of the ticks as well as interactions with other species and the role of predators and pathogens are discussed. PMID- 3329327 TI - Some avian and mammalian hosts of Amblyomma hebraeum and Amblyomma marmoreum (Acari: Ixodidae). AB - Large numbers of birds, wild mammals and domestic stock from a variety of localities within the Republic of South Africa were examined for infestation with the ixodid ticks Amblyomma hebraeum and Amblyomma marmoreum. Every warthog (Phacochoerus aethiopicus), Burchell's zebra (Equus burchelli), impala (Aepyceros melampus) and kudu (Tragelaphus strepsiceros) from the Kruger National Park in the north-eastern Transvaal Lowveld was infested with A. hebraeum. In the eastern Cape Province every helmeted guinea fowl (Numida meleagris), scrub hare (Lepus saxatilis) and kudu from the Andries Vosloo Kudu Reserve; all but 1 of the 22 domestic cattle examined on the farm "Bucklands"; and all Angora goats plus nearly all Boer goats examined on the farm "Brakhill" were infested with this tick. Most animals examined appeared to be good hosts of the immature stages, and the larger the host species the greater the chances of it harbouring large numbers of adult ticks. The largest animals examined, such as eland, buffalo, giraffe and rhinoceros, harboured very large numbers of adult A. hebraeum. No adult A. marmoreum was recovered from any host. However, 50% or more of helmeted guinea fowl and kudu from the Andries Vosloo Kudu Reserve; helmeted guinea fowl, scrub hares and eland (Taurotragus oryx) from the Mountain Zebra National Park; helmeted guinea fowl, kudu, domestic sheep, goats and cattle on the farm "Bucklands", and caracal (Felis caracal) from the Cradock and Southwell areas of the eastern Cape Province were infested with immature A. marmoreum. In the Bontebok National Park in the south-western Cape Province more than 35% of scrub hares, vaal ribbok (Pelea capreolus) and bontebok (Damaliscus dorcas dorcas) were infested with immature ticks. PMID- 3329328 TI - Danger of introducing heartwater onto the American mainland: potential role of indigenous and exotic Amblyomma ticks. AB - The existence of heartwater on 3 islands of the Central Lesser Antilles and the presence of an efficient vector originating from Africa, Amblyomma variegatum, on most of the islands of this region constitute a serious threat for livestock on the American mainland. The disease can be introduced there either by infected animals or infected ticks. The most likely way is probably the transportation of domestic animals which are heavily infested by ticks. Due to the low rate of infection of ticks in endemic areas and the low rate of infestation of wild animals by ticks, the risk of transportation by migratory birds (among which the cattle egret is the most important) seems negligible compared with domestic animals, especially ruminants and dogs. The establishment and spread of the disease on the mainland could result from indigenous American Amblyomma species, of which at least 2, Amblyomma cajennense and, more especially, Amblyomma maculatum, are experimental vectors. The biological and ecological features of these ticks conform to some extent with the characteristics necessary for them to act as vectors. They are widespread and sufficiently well adapted to ruminants to ensure the continuation of the epidemiological cycle. Disease could evolve in wild life (deer) or, as seems more likely, in livestock, of which the population density is very high on most of the mainland. However, the establishment of the disease is more likely to occur if the well adapted vector of heartwater, Amblyomma variegatum, is introduced as well. This exotic species would find environmental conditions favourable for its survival and spread in most of the tropical and subtropical Western Hemisphere. Protection of the American mainland and the disease-free islands of the area must be based on strict control of domestic animal movement in the Caribbean, on the decrease of the vector population by tick control campaigns and, if possible, on the eradication of Amblyomma variegatum from the focus of heartwater on the islands. PMID- 3329329 TI - Tick pheromones. AB - According to their activity profiles tick pheromones can be characterized as assembly pheromones, aggregation/attachment pheromones, pre-attachment or pre feeding pheromones, attractant sex pheromones, contact sex pheromones, fecundity reducing pheromone and various ungrouped pheromones. This paper gives a short review of the chemical characteristics, biological roles, and activity periods as well as the sites of production and release of tick pheromones. PMID- 3329330 TI - Biochemical studies on the salivary glands and haemolymph of Amblyomma hebraeum. AB - The functional significance of some components of salivary glands and of their secretion and of haemolymph of Amblyomma hebraeum and other tick species is reviewed with respect to host responses at the attachment site, the survival of specific pathogens in the vector, the transmission of pathogens and immunological responses of the host to tick infestation. PMID- 3329332 TI - The production of heartwater vaccine. AB - The events leading to the production of an effective vaccine against heartwater are summarized. The production techniques used at Onderstepoort to produce and control the quality of the infected blood and nymph suspension vaccines, and covering their respective advantages and disadvantages, are compared. The many problems of these vaccines and how they may be overcome are discussed. PMID- 3329331 TI - The treatment of heartwater. AB - This paper reviews the available literature on the treatment of heartwater and draws comparisons with results obtained from recent work on experimentally induced heartwater in sheep, calves and mice. PMID- 3329333 TI - The infection and treatment method of vaccination against heartwater. AB - The history of vaccination techniques against heartwater and the development of the infection and treatment method are reviewed briefly. Present techniques and their shortcomings are defined and possible areas of improvement discussed. PMID- 3329334 TI - The block method of vaccination against heartwater. AB - A critical evaluation is made of reports in the literature on the block method of vaccination and the relevant factors that play a role in the immunization against heartwater are also discussed. The most important of these is the fact that in heartwater immunogenicity parallels pathogenicity. It is shown that the more severe the reaction of the host to the immunizing infection, the stronger its immunity to subsequent challenge. The importance of this principle in the block method is emphasized. Other factors that play a role are the average incubation periods recorded in the different domestic ruminants after experimental infection and differences in age and breed susceptibility. The survival rate of experimentally infected Bonsmara cattle and Merino sheep that were treated on different days of the febrile reaction also serve as a guideline to determine the day after infection on which block treatment can be applied. The danger of a fatal recrudescent infection if block treatment is given too early, necessitating additional treatment and close observation, is indicated. In conclusion, recommendations on the day of block treatment are made for each domestic ruminant species. It is emphasized that the other methods of immunization of large groups of animals, such as treatment only after the commencement of the febrile reaction determined by the daily recording of early morning temperatures, or the prolonged prophylactic chemotherapy of susceptible stock exposed to heavy tick challenge, are preferable to the block method. The block method does, however, find application in certain instances where these procedures are impractical or inappropriate. PMID- 3329335 TI - Chemical control of the heartwater vectors. AB - This paper reviews available literature on the efficacy of acaricides against Amblyomma hebraeum and other tick species, and presents information on tests done with registered chemicals in the laboratory. Little published information is available on the efficacy of chemicals specifically against A. hebraeum. A host of formulations are registered for use as acaricides on cattle, sheep, and goats in South Africa and thus, by implication, against this species. Resistance has only been described to arsenic and toxaphene in Southern Africa; the other registered products are generally considered to be effective. In contrast, many efficacy tests of various chemicals in different formulations against other Amblyomma spp. have been described. These publications have mainly emanated from the USA, where bite-wounds of these ticks serve as oviposition sites for screwworm flies. In this paper, Amblyomma maculatum and Amblyomma variegatum are included as potential heartwater vectors. The acaricidal efficacy of a number of compounds, representative of different chemical classes, was tested in South Africa against an arsenic and organochlorine resistant strain of A. hebraeum. The engorged adult female immersion method was used. A disconcerting discovery was that several of these registered products failed to control this tick when used at their recommended concentrations. It is concluded that many chemicals which fail against A. hebraeum on cattle do so because of insufficient persistence. Exposure of this tick to lower levels of existing chemicals, but for longer periods, ought to provide satisfactory control for many years. PMID- 3329337 TI - The natural control of heartwater vectors. AB - Socio-economic factors and environmental considerations have increasingly encouraged the search for methods of tick control other than acaricidal treatment. Biological control management regimes have, so far, not proved to be sound replacements for acaricides. The major natural control methods employed successfully at present are host resistance and pasture management. The former has been extensively studied and utilized in a one-host-tick situation, and its potential specificity for the Amblyomma species is discussed. Pasture management in the form of tick-resistant plants and habitat modification affecting vector ecology and viability is discussed, as is host availability. Parasites and predators affecting tick populations are gleaned over with the accent on predacious birds (Buphagus species) which may play a limited role in integrated control programmes. Reference is made to the possibilities of genetic manipulation, problems accompanying the implementation of sterile male techniques, and hybrid sterility. In conclusion, a plea is made to ensure a thorough understanding of target vector ecology before any control measures are employed. This should be preferably from an integrated point of view rather than from a standpoint of unilateral reliance. PMID- 3329336 TI - The control of heartwater by means of tick control. AB - Two main methods are currently being used by farmers in the heartwater regions to control this disease in cattle and other stock, namely strategic control of ticks and total control of ticks. Some farmers make successful use of the latter method, particularly in areas which are marginal for the disease. Total tick control requires top managerial skills, which includes continual expert supervision, a relatively rare asset. The majority of farmers, often unintentionally, apply strategic control of ticks to control heartwater, either without or with vaccination against the disease. In this case the objective of tick control is to minimize "tick worry" without interfering too drastically with natural transmission of the disease. This method would make provision for natural immunization of young animals (a more uncertain method than vaccination) and the maintenance of immunity. In practice these methods appear to diminish deaths from heartwater appreciably, but do not protect all animals from the disease. Furthermore, they appear to be more effective in cattle than other stock. Although strategic control has an evolutionary background and considerable merit under African conditions, it is being applied in an empirical way because of paucity of information on the epidemiology of heartwater. More information on the infection rate in and infectivity of ticks (percentage of infected ticks) offer challenging research possibilities. PMID- 3329338 TI - [Major beta-thalassemia and bone marrow allograft. Two cases and a study of the literature]. AB - A 5 year 9 month-old boy has received a bone marrow allograft for beta thalassaemia major. Conditioning included busulfan: 16 mg/kg, cyclophosphamide 200 mg/kg and a (6 Gy) thoracoabdominal irradiation. After a 16 months follow-up, the child is currently in complete remission without treatment with all the markers of his donor. His 9 year-old sister has been allografted for beta thalassaemia major, with the same conditioning regimen. After engraftment, rejection occurred at day 85 with severe aplastic anaemia. A second graft was performed with the same donor without engraftment and the patient died at day 18 of pneumonitis. A review of the literature is proposed and the ethical choices are discussed. PMID- 3329339 TI - A case report and review of deciduous molar ankylosis. PMID- 3329341 TI - Assessment of animal models for investigating the cardiovascular adaptations to obesity. AB - Several animal models of obesity have been reviewed with respect to the cardiovascular adaptations to this disorder. While some cardiovascular data are available for each model reviewed, the spontaneously obese rat has been most extensively characterized. Biochemical adaptations of the myocardium to experimental obesity have been reported, but this area has not been investigated extensively. The combined effects of obesity and hypertension upon the heart have been observed recently in the aortic-coarcted, obese rat, which may serve in the future as a useful model for investigating the basis of heart failure that occurs when these disorders are observed concurrently in the clinical setting. PMID- 3329340 TI - Cell-mediated immune functions in multiple sclerosis. PMID- 3329342 TI - [An appraisal of the criteria of cerebral death. Review of the literature and the usefulness of single photon emission CT]. PMID- 3329343 TI - [Problems of the vegetative state]. PMID- 3329345 TI - Retraction. PMID- 3329346 TI - [Breast cancer. Diagnosis and prognosis--what is the status in 1987?]. PMID- 3329344 TI - Immunohistochemical studies of colorectal carcinoma with a monoclonal antibody against carcinoembryonic antigen. AB - Immunoperoxidase localization of carcinoembryonic antigen (CEA) was performed on tissue sections of colorectal carcinoma using a monoclonal antibody (MAb) against CEA. CEA has been demonstrated in 20 out of 22 rectum carcinomas (90.9%), in all of 23 colonic carcinomas, in none of 4 hyperplastic polyps and in 2 out of 6 adenomatous polyps (33.3%). CEA was found more often, and the intensity of the staining was stronger in well-differentiated carcinomas than in moderately and poorly differentiated carcinomas. No correlation was found between the presence of CEA in colorectal carcinoma and the stages of the disease. The mean values of serum CEA in patients with colorectal carcinoma and polyps with negative, weakly and strongly positive staining were 5.4 +/- 3.9 ng/ml, 28.3 +/- 23.8 ng/ml and 99.8 +/- 145.3 ng/ml respectively. Elevation of serum CEA occurred in 30 out of 39 (78.9%) cases with strongly positive CEA staining, in 4 out of 6 (66.7%) with weakly positive and in 1 out 9 (11.1%) with negative staining. A significant difference was found in serum CEA activity between the group with negative CEA staining and positive CEA staining (P less than 0.01). Our results suggest that the monoclonal antibody (MAb C27) can be used for the localization of CEA in conventionally prepared tissues of colorectal carcinomas by immunoperoxidase techniques for routine immunopathological diagnosis. PMID- 3329347 TI - Psychotherapy for the cancer patient. PMID- 3329348 TI - The use of psychotropic medication in cancer patients. PMID- 3329350 TI - Psychosocial consequences of prostate cancer--my father's illness and review of literature. PMID- 3329349 TI - Behavioral approaches for the management of adversive side effects of cancer treatment. PMID- 3329351 TI - Sexual problems in cancer patients and their management. PMID- 3329352 TI - Consultation and liaison issues in cancer care. PMID- 3329354 TI - Behavioral modification in the treatment of smoking. PMID- 3329353 TI - Lifestyle and cancer prevention. PMID- 3329355 TI - [Hypnotic effect of homeopathic medication and placebo. Evaluation by double blind and crossing technics]. PMID- 3329356 TI - Radiology of lumbar vertebral pedicles: variants, anomalies and pathologic conditions. AB - Close scrutiny of the size, shape, density and margins of the pedicles may permit the clinical radiologist to suggest a wide variety of systemic diseases. PMID- 3329358 TI - Heterotopic heart transplantation: a radiographic review. AB - Heterotopic heart transplantation can be performed in the presence of high pulmonary vascular resistance. The authors call attention to a rare, but potentially life-saving procedure. PMID- 3329357 TI - Is the community radiation oncologist ready for clinical hyperthermia? AB - The author, in assessing this "new" therapeutic modality, clearly identifies the many problems associated with it and emphasizes its still experimental nature. PMID- 3329359 TI - Sonography of the pancreatic head aided by water and glucagon. AB - The administration of water and glucagon facilitates the ultrasonic evaluation of the pancreas in the author's experience. He believes it obviates the need for more costly CT in most cases. PMID- 3329360 TI - Ultrasound case of the day. Twin pregnancy, intrauterine death of one twin with disseminated intravascular coagulation resulting in the development of a cerebral infarct in the surviving twin. PMID- 3329361 TI - Ultrasound case of the day. Resolving hepatic and duodenal (retroperitoneal) hematomas. PMID- 3329362 TI - The use of transrectal ultrasound in the diagnosis, guided biopsy, staging and screening of prostate cancer. AB - In the authors' experience, transrectal sonography has the ability not only to stage prostatic cancer accurately, but also to detect such lesions before they become palpable. PMID- 3329363 TI - Radiographic evaluation of modern orthopedic fixation devices. AB - Orthopedic surgeons employ a wide variety of modern fixation devices in the treatment of fractures. In order to assess these instruments correctly, the radiologist should be aware of both their purpose and their normal appearance. A review of the common internal and external fixation devices used at a major trauma center and the complications of their use has been presented. PMID- 3329364 TI - Pediatric case of the day. Abdominal aortic aneurysm in a patient with tuberous sclerosis. PMID- 3329365 TI - Ultrasound case of the day. Neurofibroma. PMID- 3329366 TI - [Lupus and pregnancy]. PMID- 3329367 TI - [Fine-needle puncture-aspiration of the breast as a preoperative diagnostic technic: evaluation of the method and review of the literature]. PMID- 3329368 TI - [Hypersensitivity of the carotid sinus: critical review]. PMID- 3329369 TI - [Spontaneous peritonitis in liver cirrhosis caused by Streptococcus group B (S. agalactiae): 2 cases]. PMID- 3329370 TI - [Segmental autotransplant of the pancreas to the neck in the dog]. PMID- 3329372 TI - [Rheological properties of sputum and expectorants]. PMID- 3329371 TI - [Diagnostic importance of ultrasonic non-visualization of the gallbladder as a sign of gallbladder disease]. PMID- 3329373 TI - [Neural control of the heart]. PMID- 3329374 TI - [Ultrasound in the diagnosis and percutaneous drainage in hepatic abscess]. PMID- 3329375 TI - [Digestive hormones]. PMID- 3329376 TI - [Sydney Ringer and the discovery of the isotonic solution in 1882. Hommage by reason of the 1st centennial]. PMID- 3329377 TI - [Phenotypic characteristics and insulin secretion in 25 cases of non-insulin dependent diabetes mellitus, subtype MODY (maturity onset diabetes in the young people)]. PMID- 3329378 TI - [Frequency of diabetes mellitus and beta pancreatic secretion in offspring of patients with MODY (maturity onset diabetes in the young)]. PMID- 3329379 TI - [The variety MODY of diabetes mellitus]. PMID- 3329380 TI - [Sydenham's chorea in the Southeastern Metropolitan Service: epidemiological report]. PMID- 3329381 TI - [Deposits of amyloid substance and plasma levels of beta 2 microglobulin in patients in chronic hemodialysis]. PMID- 3329382 TI - [Genes and chromosomes in common diseases]. PMID- 3329383 TI - [The present-day course of rheumatism and the evolution of rheumatic heart defects in adults (clinico-morphologic study)]. PMID- 3329384 TI - [Detection of patients with reactive urogenic arthritis]. PMID- 3329385 TI - [Possibilities of roentgenography using direct image magnification and processing by analog computers in the differential diagnosis of primary osteoarthrosis deformans and rheumatoid arthritis]. PMID- 3329386 TI - [Ultrastructure and function of thrombocytes in children with rheumatoid arthritis]. PMID- 3329387 TI - [Oxygen supply and capillary blood flow in the skin of patients with scleroderma (data on complex polarography)]. PMID- 3329388 TI - [Use of laser Doppler flowmetry in various rheumatic diseases]. PMID- 3329389 TI - [Differential diagnosis of dilated cardiomyopathy and rheumatic heart defects]. PMID- 3329391 TI - [The development of rheumatology in Soviet Lithuania]. PMID- 3329390 TI - [Surgical treatment of combined mitral and aortic heart defects]. PMID- 3329393 TI - [Behcet's syndrome]. PMID- 3329392 TI - [Involutional osteoporosis]. PMID- 3329395 TI - Biochemical and immunologic diagnosis of cancer. Growth factors and growth factor receptors. PMID- 3329394 TI - [Pediatric aspects of the classification and nomenclature of rheumatic disease (discussion of the plan for the classification and nomenclature of rheumatic diseases, 1986)]. PMID- 3329397 TI - Biochemical and immunologic diagnosis of cancer. Central nervous system tumors. PMID- 3329396 TI - Biochemical and immunologic diagnosis of cancer. Neuroblastoma. PMID- 3329398 TI - Biochemical and immunologic diagnosis of cancer. Melanoma. PMID- 3329400 TI - Biochemical and immunologic diagnosis of cancer. Myeloma. PMID- 3329399 TI - Biochemical and immunologic diagnosis of cancer. Leukemia and lymphoma. PMID- 3329401 TI - Biochemical and immunologic diagnosis of cancer. Molecular probes and tumors in general. PMID- 3329402 TI - Biochemical and immunologic diagnosis of cancer. The timing of tests in tumor monitoring. PMID- 3329403 TI - Biochemical and immunologic diagnosis of cancer. General cancer tests. PMID- 3329404 TI - Biochemical and immunologic diagnosis of cancer. Colorectal cancer. PMID- 3329405 TI - Biochemical and immunologic diagnosis of cancer. Renal and transitional carcinomas. PMID- 3329406 TI - Immunoadsorbent purification of carcinoembryonic antigen using a monoclonal antibody: a direct comparison with a conventional method. AB - Carcinoembryonic antigen (CEA) has been extracted and purified by two different methods from a single aqueous homogenate of liver metastases from a primary adenocarcinoma of the colon, thus enabling direct comparison to be made between a conventional technique using gel filtration and a monoclonal antibody immunoadsorbent method. Yield, immunoreactivity and purity have been determined in both cases by direct weighing, enzyme-linked immunoadsorbent assay, radioimmunoassay and SDS-polyacrylamide gel electrophoresis. Reactivity of the antigen with monoclonal and polyclonal anti-CEA antibodies recognising different epitopes was analysed by Western blotting. There appears to be no significant difference in immunoreactivity or purity by these criteria, but the immunoadsorbent method gave a higher yield of CEA for far less expenditure of time and effort. A variant of CEA with a lower molecular weight was also identified in both preparations. PMID- 3329407 TI - Nonesterified fatty acids: role in the molecular events linking endocrinology and oncology via nutrition. AB - It is more and more clear from recent studies that both steroid and peptide (hormone and growth factor)-mediated pathways of mitogenesis are closely linked. These two pathways are intertwined into a highly regulated network. The two main points of connection are at the level of lipase and protease biosynthesis and regulating systems. Both enzymes are steroid-regulated. Furthermore, free fatty acids can be considered as positive or negative common modulators and/or messengers of the steroids and the peptide factors regulating the mitogenic processes. PMID- 3329408 TI - Immunization in urban Southeast Asia. AB - By the year 2000 half the population in the world is expected to reside in large urban areas. "Improving immunization services to the disadvantaged in urban areas" is considered one of the priorities for the Expanded Programme on Immunization (EPI). A review of the current situation with regard to immunization coverage and disease surveillance in urban Southeast Asia shows that acceleration of immunization activities in urban areas is needed to achieve and sustain the goal of Universal Child Immunization by the year 1990. PMID- 3329410 TI - Immunoperoxidase study on paraffin sections of gastrointestinal lymphoreticular lesions. AB - Seventy-five cases of lymphoreticular lesions of the gastrointestinal tract were studied by the immunoperoxidase method on paraffin sections which demonstrated cytoplasmic markers, in particular immunoglobulin (Ig) in B-lymphocytes and alpha 1-antichymotrypsin in histiocytes. There were 4 cases of benign immunoproliferative disease (IPD), 1 in the stomach, 3 in the small intestine; their reactions were polyclonal. Large cell non-Hodgkin's lymphoma was subdivided into 21 cases with IPD ("Mediterranean Abdominal Lymphoma") and 29 cases without. Eight cases of lymphoma with IPD were gastric and 13 intestinal; 7 gastric and 12 intestinal lymphomas were of B-cell origin; 1 gastric tumour was histiocytic; 1 intestinal neoplasm had no detectable marker. Sixteen cases of lymphoma without IPD were gastric and 13 intestinal; 4 gastric and 4 intestinal lymphomas were of B-cell type; 3 gastric and 2 intestinal neoplasms were histiocytic; 1 intestinal tumour was a composite of B-cells and histiocytes, in separate but contiguous foci; 9 gastric and 4 intestinal lymphomas had no identifiable marker. One of 18 cases of mixed and small cell lymphoma was accompanied by IPD. In these types of lymphoma Ig was found only in 10-30% of cells, mainly with plasmacytoid differentiation. PMID- 3329409 TI - In vitro mefloquine resistance of Plasmodium falciparum isolated from the Burmese border region of Thailand. AB - The in vitro susceptibility of twenty isolates of Plasmodium falciparum from Tha Song Yang, Tak province, Thailand were determined. The isolates were resistant to chloroquine (IC50 = 220 nM; MIC = 762 nM), quinine (IC50 = 252 nM; MIC = 1010 nM), and pyrimethamine (IC50 = 16400 nM; MIC = 43100 nM) but generally sensitive to mefloquine (IC50 = 6.90 nM; MIC = 20.9 nM) and halofantrine (IC50 = 8.73 nM; MIC = 2.71 nM). Two isolates were identified which appeared resistant to mefloquine (IC50 = 23.1 nM; MIC = 56.6 nM). These isolates may represent an extension of a population of parasites from eastern Thailand. PMID- 3329411 TI - Spleen in falciparum malaria: ultrastructural study. AB - An ultrastructural study was undertaken of the spleen of 13 year-old-boy who died of falciparum malaria. The spleen revealed the following: both parasitized and non-parasitized erythrocytes are phagocytosed in large numbers by macrophages, littoral and reticular cells. Blood congestion and trapping of parasitized erythrocytes are commonly seen in splenic sinusoids and cords. Erythrocytes forming rosette structure around immuno-presenting cells is observed. The results of this study provide evidence that the mechanisms underlying splenic host defence in malaria include both immunological and non-immunological interaction with erythrocytes. Splenic trapping of parasitized erythrocytes is an important defence mechanism and the phagocytosis of erythrocytes probably accounts for anaemia. PMID- 3329413 TI - Detection of specific IgM in dengue infection. AB - A modification of the IgM-capture ELISA which can provide an early diagnosis for dengue infection is presented. The test is technically simple compared to HI and appears to be more sensitive. It has the advantage over HIT for the detection of specific IgM in that it is more sensitive and the reading of the result is not subjective. There is the possibility of the test being able to replace HI and HIT in the future. PMID- 3329414 TI - [The problems of infection after total joint replacement]. PMID- 3329412 TI - Analysis of Opisthorchis viverrini antigens: physicochemical characterization and antigen localization. AB - Antigens of Opisthorchis viverrini were identified and characterized by enzyme linked immunosorbent assay, polyacrylamide gel electrophoresis following radioimmuno-precipitation, and indirect immunofluorescence. The immunoreactive protein with a relative molecular weight (Mr) of 89 kD was the predominating component of the parasite metabolic products. An immunofluorescence study showed it to be associated with parasite eggs, linings of the reproductive system and secretions therein. Protein of the surface tegument had Mr of greater than 116, 108, 64, 38, 34, 20 and 16-17 kD. The 16-17 kD surface molecule was the predominant protein, representing approximately 50% of the total protein in crude aqueous extracts of adult worms. However, it was poorly immunogenic when compared with the 89 kD molecule. Together with data presented previously, it appears that in addition to the 89 kD protein, several tegumental molecules are also specific for O. viverrini and have immuno-diagnostic potential. PMID- 3329415 TI - [Clinical trials of nabumetone in therapy of rheumatoid arthritis]. PMID- 3329416 TI - Social work in health care: needs, challenges and implications for structuring practice. AB - A structured multivariate practice model is proposed for improving social workers' capabilities to effectively satisfy patients' psychosocial needs. The model bases practice activities on an explicit theoretical framework. Using this approach may enhance the professional authority social work needs but which the biomedical framework of existing health care delivery systems frequently threatens: to autonomously make informed decisions to meet the psychosocial needs of populations at risk. The approach can also contribute to the development of an indigenous professional body of knowledge. PMID- 3329418 TI - Intrinsic regulation of the blood flow to the endocrine and exocrine parts of the rat pancreas. AB - To evaluate possible differences in the local regulation of blood flow between the endocrine and exocrine pancreatic parenchyma, the blood perfusion of the pancreas and the pancreatic islets has been measured after a 90-second period of anoxia or a 5-min period of increased venous pressure. After anoxia, caused by interruption of arterial blood flow, there was a significant increase (P less than 0.01) in islet blood flow (IBF) while whole pancreatic blood flow (PBF) remained unchanged. Arterial occlusion also increased the serum glucose (P less than 0.01) and serum insulin concentrations (P less than 0.001). Vagotomy prevented the increase in IBF but did not affect the increase in serum glucose or serum insulin concentration, which suggests that the increase in IBF was due to the increased serum glucose concentration. An increased venous pressure in the portal vein did not affect IBF, PBF, serum glucose or serum insulin concentrations. It is concluded that, in the rat pancreas, the local control of PBF and IBF is of minor importance in the regulation of blood flow. PMID- 3329417 TI - Computed tomography-controlled stereotactic surgery: the logic and the operative procedures. PMID- 3329419 TI - Relations between clinical signs of right and left cardiac decompensation and radiological signs thereof. AB - Ten consecutive patients arriving at the emergency department for severe systemic cardiac decompensation were investigated in respect of 17 clinical and laboratory parameters indicative of right or left heart failure. Investigations were made at arrival to the hospital and after completed in-hospital care. In respect of left heart failure the presence of rales and signs of interstitial oedema had a similar sensitivity. Both were of diagnostic value. Right heart failure was best diagnosed with clinical parameters such as pitting oedema, filling of the jugular vein, and liver enlargement. The laboratory parameters were less sensitive and appeared to have not a diagnostic but well a confirmatory value. PMID- 3329420 TI - Early and late discharge after hospital birth. Health of mother and infant in the postpartum period. AB - Early discharge, defined as hospital leave 24-48 hours after birth, was introduced at Falun Hospital in 1984. 164 women interested in participating in an evaluative study of the program were randomly allocated in late pregnancy to an Experimental group (EG) offered early discharge, and a Control group (CG) offered the regular postpartum care in hospital. After medical and other withdrawals 24 h after the birth, 50 women remained in EG and 54 in CG. Infant morbidity and number of prescribed medicaments during the first 6 months after the birth were lower in EG than in CG, but the difference was not statistically significant. EG mothers made fewer visits to the Child Health Centre nurse than did CG mothers (p less than 0.05). No significant difference in puerperal complications was demonstrated, but the intake of sedatives by EG mothers was smaller than that of CG mothers during the first puerperal week (p less than 0.01). PMID- 3329421 TI - Detection of ABH antigens via exfoliated urinary cells. A preliminary report. AB - The expression of ABH blood group antigens of bladder carcinomas heralds a relatively benign clinical course, whereas the antigen's deletion in tumors is often predictive of tumor recurrence and invasion. Using exfoliated urinary cells, we tried the prospective detection of ABH antigens. Though interpretations were independent, the status of antigens on exfoliated cells accorded with that on tissue sections. Detection of blood group antigens via exfoliated urinary cells is a noninvasive, reliable test that could be used for screening and surveillance of patients with bladder tumors. This method permits monitoring of patient ABH isoantigens by prospective screening. PMID- 3329422 TI - Renal cell carcinoma with heterotopic bone formation. Case report and review of the Japanese literature. AB - A case of renal cell carcinoma with heterotopic bone formation is presented. We will review the reports and radiographic findings of Japanese cases and comment on their hypovascularity. PMID- 3329423 TI - Spontaneous regression of pulmonary metastasis from renal pelvic cancer. AB - A case of spontaneous regression of multiple pulmonary metastases of transitional cell carcinoma is reported. Spontaneous regression of metastatic pulmonary lesions seldom occurs in transitional cell cancer, and only 3 such cases have been reported in the literature. A 42-year-old male with multiple pulmonary metastases which had regressed spontaneously for a significant period of time is herein reported. The lesions were shown to be transitional cell carcinoma, originating from the left renal pelvis. The serial immunological examinations suggest that the phenomenon might be attributed to the augmented immune response of the patient. PMID- 3329424 TI - [Construction of a typhoid-dysentery bivalent strain with typhoid ty21a and dysentery T32-Istrati strains]. PMID- 3329425 TI - [The isolation and identification of a Clostridium botulinum type D strain]. PMID- 3329426 TI - Illness-engendered poverty among the elderly. AB - This paper presents an overview of the economic situation of elderly women in the United States. Its focus is on "illness-engendered poverty," a type of poverty that results from the inadequacies of Medicare coverage of long-term care and the subsequent need of many elderly to "spend down" into poverty in order to qualify for means-tested, publicly financed health and social programs. The consequences of Medicaid eligibility requirements and system incentives on the economic and social well-being of older women and their families are discussed. PMID- 3329427 TI - Changing patterns of health insurance coverage: special concerns for women. AB - Health care expenditures and utilization have increased dramatically in recent years, but gaps in health insurance coverage restrict access to care for a growing portion of the population. Women are especially vulnerable given the structure of insurance coverage and demographic factors. The erosion of insurance coverage can be attributed to several trends, particularly employer cost containment strategies, restricted public program eligibility and changes in the characteristics of the work force. Numerous measures have been adopted at the federal and state levels to maintain or expand coverage on an incremental basis. As broader segments of the population suffer reduction or loss of coverage, a comprehensive approach will be necessary to ensure universal access to health care. PMID- 3329428 TI - A research agenda on issues affecting poor and minority women: a model for understanding their health needs. AB - Acquiring data on quality of life indicators such as health, mental health and family roles of poor and minority women remains a low research priority. This paper provides an assessment of current knowledge in this area and an overview of the context in which poor and racial/ethnic women utilize health care services. A model that encompasses the interactive effects of race, gender and class variables is proposed. Such a model is a necessity for understanding the health needs of poor and racial/ethnic women. Suggestions for future research and policy formulation are given. PMID- 3329429 TI - Is being poor a mental health hazard? AB - From a perspective of needs, risks and tasks of women throughout the life and family cycle the paper examines relationships between mental health and poverty by reviewing observed determinants and concomitants of poverty as well as stressors and risks associated with women's socioeconomic position, environmental conditions, and social roles. As a tool for policy development, a three-anchor needs proposition and a coping schema and formula are proposed as a new conceptual framework for appraising women's hazards and strengths. The poverty status of women in Canada is also reviewed. PMID- 3329431 TI - [The forgotten body. Phenomenologic remarks on the body, soul and disease]. PMID- 3329430 TI - [Critical analysis of cognitive therapies from the viewpoint of the Lazarus and Weiner cognitive emotions theories]. PMID- 3329433 TI - Regulation of protein kinase C and its role in metabolic regulation and cell proliferation. PMID- 3329432 TI - [Vitamin D status of the aged subject]. PMID- 3329434 TI - [The neuropsychology of the emotions and personality structure]. PMID- 3329435 TI - [Rapid and simple technic for the isolation of Cladosporium carrionii in samples of xerophilic vegetation]. PMID- 3329436 TI - Age dependent effect of toxic and detoxified endotoxins on the natural anti-DNA antibody level in rats. AB - Toxic endotoxin (LPS) and its irradiated detoxified form (RD-LPS) induced only small changes in the DNA level in the sera of 4, 12 and 18 months old rats. Changes in the anti-DNA titres were age-dependent. In 4 months old rats one or two injections of the LPS preparations failed to increase the circulating anti DNA level. In 12 and 18 months old rats both toxic and detoxified LPS preparations raised the anti-DNA titres. The second LPS injection evoked a smaller response in 18 months old rats than the first one. PMID- 3329437 TI - The effects of cannabinoids and cannabispiro compounds on Escherichia coli adhesion to tissue culture cells and on leukocyte functions in vitro. AB - delta 9-Tetrahydrocannabinol, cannabidiol, cannabidiolic acid, tetrahydrocannabidiolic acid, cannabispirol, acetylcannabispirol, cannabispirone, and cannabispirenone in a low concentration did not affect the adhesion of Escherichia coli on cultured HEp-2 cells. Cannabinoids at 10(-6) M increased the chemiluminescence of human polymorphonuclear leukocytes, while the cannabispiro compounds failed to enhance the oxidative burst of leukocytes. In lymphocyte and granulocyte function tests (E- and EA-rosette formation, blast transformation of T-lymphocytes in the presence of phytohaemagglutinin and concanavalin-A, ADCC and phagocytosis) all compounds displayed immunosuppressive effect at 1.5 X 10(-5) M. Tetrahydrocannabidiolic acid exerted the weakest immunosuppression on human leukocyte functions. PMID- 3329438 TI - Effect of organic volatiles from Saccharomyces on the spore germination of fungi. AB - Common volatile organic compounds (acetaldehyde, ethylacetate, ethanol, n propanol, isobutanol, 2-methyl-butanol, 3-methyl butanol) tested singly and in combination inhibited the spore (conidium) germination of Helminthosporium oryzae, Cercospora personata, Cunnighamella blakesleeana, Colletotrichum capsici, and Alternaria solani. PMID- 3329439 TI - The effect of luteinizing hormone releasing hormone (LHRH) on steroidogenesis by the human luteal tissue. AB - The effect of luteinizing hormone releasing hormone (LHRH) on progesterone and estradiol production was studied in human luteal tissue. Tissue slices were incubated in Ham's F-10 medium under an atmosphere of 95% O2: 5% CO2 at 37 degrees C for 4 h. Slices were treated with or without human chorionic gonadotropin (HCG) in the presence or absence of LHRH. HCG stimulated progesterone and estradiol production by human luteal tissue in a time- and dose related manner. LHRH stimulated the basal progesterone production in five (one early luteal and four mid-luteal) of 17 corpora lutea, and stimulated the basal estradiol production in three (all mid-luteal) of 16 corpora lutea. On the other hand, LHRH inhibited HCG-stimulated progesterone production in four (two early luteal and two mid-luteal) of 22 corpora lutea, and inhibited HCG-stimulated estradiol production in four (one early luteal and three mid-luteal) of 18 corpora lutea. In the acute short-term incubations of human luteal tissue, therefore, LHRH had little effect on basal and HCG-stimulated steroidogenesis. However, in a few corpora lutea taken in the early or mid-luteal phase, LHRH stimulated basal steroidogenesis and inhibited HCG-stimulated steroidogenesis. PMID- 3329440 TI - Search for circulating immune complexes and activation of the complement system in relation to estrogen treatment. AB - By employing an ammonium sulphate precipitation technique, previous studies have shown circulating immune complexes (cIC) in an increased proportion of women using oral contraceptives, as compared with non-users. The pathogenicity of cIC is well established, as deposition in organs may lead to activation of the complement system and thereby inflammation and tissue destruction. The purpose of the present study was to determine whether estrogen treatment could induce the formation of cIC, as measured by more specific immune complex assays. To test for complement activation, plasma samples were analysed for the complement split product C3d. Thirty-one women treated with estrogen for menopausal hormone deficiency symptoms and 38 untreated controls were analysed for cIC. Using a solid-phase C1q-anti-IgG binding assay, the mean level of cIC in the estrogen treated group did not differ significantly from that of the untreated control group (p greater than 0.05). In a solid-phase C1q-protein A binding assay a very small average increase in the cIC values for the estrogen-treated group in comparison with the untreated group was found, expressing a significant difference (p = 0.04). Moreover, the C3d levels for the estrogen-treated group did not differ from the untreated control group. Finally, no differences could be demonstrated in cIC and C3d levels between patients treated with synthetic estrogens and patients treated with natural estrogens. PMID- 3329442 TI - Sinusoidal-like fetal heart-rate pattern. Real-time ultrasound may help in differential diagnosis. AB - Cases of benign sinusoidal-like fetal heart-rate pattern, associated with rhythmic movements of the fetal mouth, are reported as probably physiological. The importance of fetal behavior observation during prepartum fetal heart-rate monitoring is stressed as a quick way to improve diagnostic accuracy in similar cases. PMID- 3329441 TI - Warm tub bath during delivery. AB - In a prospective study, 88 women bathed in a warm tub bath for 1/2-2 hours during first stage labor after a strictly normal pregnancy, ending with spontaneous onset of labor at term. A control group consisted of 72 women fulfilling the same criteria of normality during pregnancy and labor, but who did not want to take a warm tub bath during labor. Apart from the bath, the two groups followed the usual obstetric procedures of the Department. The cervical dilatation in the "bath group" was 2 1/2 cm/h compared with 1 1/4 cm/h in the "control group". Mean pain score in the bath group was higher at the start of the study, before the bath, and they experienced a pain relief during bath which was not observed in the control group. This difference may be due to bias. The use of morfica and the need for stimulation of labor contractions were both twice as high in the control group, but this difference was not significant. No differences were observed with regard to operative delivery, vaginal or perineal laceration or in bleeding during labor or postpartum. The total duration of labor was the same in the two groups and no differences in neonatal condition were observed. The bacterial contamination of the bath water was insignificant and there were no significant febrile episodes post partum. PMID- 3329443 TI - Disappearance of human chorionic gonadotropin following removal of the fetus and placenta left in situ in a case of advanced abdominal pregnancy. AB - In a case of abdominal pregnancy, human chorionic gonadotropin (hCG) was determined twice during the first trimester and serially after removal of the fetus and placenta left in situ. From the 5th to the 7th week of gestation, the hCG values increased, from 5980 to 10000 U/l. After operation the hCG level decreased to 197 U/l after 51 days and hCG was not detectable 72 days postoperatively. PMID- 3329444 TI - Discrepancy between aldosterone production and renin-angiotensin system activity in Brattleboro rats. AB - It was demonstrated before that in addition to their typical changes in water sodium-potassium balance Brattleboro rats, homozygous for hypothalamic diabetes insipidus (DI), revealed a discrepancy between aldosterone level and plasma renin activity (PRA). In the present study PRA was significantly increased (79%), and concomitantly juxtaglomerular (JG) index was increased, reflecting an increased secretory activity of renin-producing JG cells. Plasma concentration of aldosterone was significantly lower (-36%) in DI rats than in their Long Evans (LE) controls. Adrenal blood flow rates were not significantly different in both groups of rats but aldosterone concentrations in the adrenal venous effluents were significantly lower (-66%) in DI rats than in LE rats, suggesting that in vivo production rate of aldosterone was reduced in DI rats. This assumption was confirmed by morphometric data of zona glomerulosa. Our results demonstrated a significant reduction (50%) of angiotensin II receptors in the adrenal glands of DI rats, referring to the number of binding sites and to Kd. This finding threw light on the dissociation between a decreased aldosterone production and stimulated renin-angiotensin system in DI rats. PMID- 3329445 TI - Neurocognitive impairment in alcoholics: review and comparison with cognitive impairment due to AIDS. AB - This review indicates that cognitive dysfunction and dementia, specifically caused by chronic alcohol use, consist of subtle changes in cognition which are easily missed and/or forgotten. The nature of the dysfunction and specific neuropsychiatric and neurodiagnostic tests will be reviewed. There are important treatment implications regarding these subtle changes in mental function. Treatment implications will also be summarized. Finally, a comparison will be made between the cognitive impairment experience by patients with Acquired Immune Deficiency Syndrome from that experienced by alcoholics. PMID- 3329446 TI - The response of state agencies to AIDS, addiction, and alcoholism. AB - State agencies have been profoundly impacted by the AIDS epidemic. In the absence of a vaccine that would prevent AIDS or of medicines that would cure it, the primary strategies of such agencies have focused on reducing the spread of AIDS by promoting cessation of high risk behaviors and thus preventing or slowing its transmission. Recent research indicates that the primary route of AIDS transmission into the general heterosexual population is by intravenous (IV) drug abusers, who directly account for about 17% of AIDS cases nationwide. Reducing the spread of AIDS within this group would not only reduce the overall toll of the disease but should limit its spread to the population at large. Infection by the human immunodeficiency virus (HIV) can be minimized by reducing or eliminating certain high-risk activities. In the IV drug using community, the primary intervention strategies include: educating IV drug users about the hazards of AIDS and sharing of needles; enrolling them in treatment programs to reduce drug use; promoting the use of new or sterilized syringes and needles among those who will not abstain from drug use; and discouraging high-risk sexual activity among those who are already infected by HIV. The State of California has already increased the number of treatment slots for IV drug users and, through the Department of Alcohol and Drug Programs, is scaling up its educational, prevention, and intervention activities, particularly those related to safe sex, promoting the cessation of IV drug use, and improving equipment hygiene by those who continue use. PMID- 3329447 TI - Acquired immune deficiency syndrome and chemical dependency. PMID- 3329449 TI - The impact of AIDS on the chemical dependency field. PMID- 3329450 TI - Alcohol and drugs as co-factors for AIDS. AB - Opiate use in humans is associated with a reduction in the number of circulating T-lymphocytes and in their ability to undergo transformation, probably resulting from opiate binding to T-cell antigens. (See Table 4). Patients also manifest a diffuse hyperglobulinemia, without change in circulating B-cell numbers. In vitro exposure of rodent and human lymphocytes to cannabinoids depresses their transformation, natural killer activity, and interferon production. Similar results occur with in vivo exposure of rodents, but data in man are mixed. Cannabinoids also inhibit primary and secondary antibody responses in rodents. Data regarding the effects of CNS stimulants are too scanty to allow comment. Barbiturate anesthesia in man and animals produces a short-lived depression of lymphocyte transformation, NK activity, and ADCC; no studies of the effects of chronic exposure have been performed. Amyl nitrite has not been proven to possess any immunosuppressive activity. PMID- 3329448 TI - AIDS update--1987. AB - Human immunodeficiency virus (HIV) infection produces a spectrum of clinical syndromes, progressing in severity from asymptomatic infection through the life threatening diseases of the acquired immunodeficiency syndrome (AIDS). Current knowledge about the epidemiology, virology, and clinical manifestations of HIV infection and AIDS are reviewed. PMID- 3329451 TI - [Biochemical aspects of an endotoxin model for endogenous uveitis]. PMID- 3329452 TI - [The origin of fibronectin in healing corneal epithelial wounds evaluated by immunoelectron microscopy]. PMID- 3329453 TI - [Clinical studies of gamma-seminoprotein in prostatic disease. I. Clinical evaluation of serum gamma-seminoprotein]. AB - Serum gamma-seminoprotein (gamma-Sm) in patients with prostatic disease was determined by enzyme immunoassay. A total of 136 patients including 13 untreated and 40 treated patients with prostatic cancer, 45 patients with benign prostatic hyperplasia (BPH) and 38 patients with other urological diseases were analyzed. The mean +/- SD of serum gamma-Sm in the 13 patients with untreated prostatic cancer and the 45 patients with BPH was 31.7 +/- 46.1 and 3.7 +/- 6.6 ng/ml, respectively, there being a statistically significant difference between the two groups. All patients with untreated stage A or B prostatic cancer had a serum gamma-Sm of less than 4 ng/ml (cut off value). The mean level of serum gamma-Sm was 5.1 +/- 1.9 ng/ml for all patients with untreated stage C prostatic cancer; 66% of them had a value above the cut off value. However, it was 55.9 +/- 52.6 ng/ml in all patients with untreated stage D prostatic cancer; 87.5% of them had a value above the cut-off value. These results suggest that gamma-Sm may be a useful tumor marker in the management of patients with prostatic cancer. PMID- 3329454 TI - [Clinical studies of gamma-seminoprotein in prostatic disease. II. Immunohistochemical study of gamma-seminoprotein]. AB - Localization of gamma-seminoprotein (gamma-Sm) was examined using horseradish peroxidase-labeled anti-gamma-Sm antibody (Chugai Corp. Ltd., Tokyo, Japan) by the enzyme-labeled antibody method in paraffin embedded specimens of 18 benign prostatic hyperplasias and 32 untreated prostatic cancers. The level of serum gamma-Sm was also determined by enzyme immunoassay in 10 untreated patients with prostatic cancer and 18 with benign prostatic hyperplasia. Specific gamma-Sm staining was detected in prostatic glandular epithelial cells and prostatic secretion of all specimens of benign prostatic hyperplasias and a half of the specimens of prostatic cancers. Specific gamma-Sm staining was shown to correlate with histological differentiation of the prostatic cancer, but no correlation was found between specific gamma-Sm staining and the level of serum gamma-Sm. PMID- 3329455 TI - [A case report: surgical reconstruction of the external genitalia in adrenogenital syndrome]. AB - This is a case report of a 5-year-old girl with congenital adrenal hyperplasia (CAH) who had clitoral hypertrophy and vagina opening at verumontanum between the bladder neck and external urethral sphincter. Female pseudohermaphroditism with CAH is the most common type of intersex problem seen in children. In females with this disorder, the internal genital organs are usually normal, but variable degrees of virilization can be observed externally. We discussed the indication of the surgical correction of ambiguous external genitalia in this syndrome in view of sexual function and cosmetic problems. PMID- 3329456 TI - [Squamous cell carcinoma of renal pelvis: a case report and review of the Japanese literature]. AB - Squamous cell carcinoma of renal pelvis is relatively rare and its prognosis is very poor. A 72-year-old man was introduced to our institute because of macroscopic hematuria. He had no history of urolithiasis or urinary tract infection. Excretory urography showed a nonfunctioning right kidney. Cytologic examination of urine was positive for malignant cell from squamous cell carcinoma. Preoperative diagnosis was made as right renal pelvic tumor, but it appeared to be renal tumor on the roentgenogram. Right radical nephrectomy and transurethral ureterectomy was performed. Radiation therapy was done after operation. Pathological diagnosis was squamous cell carcinoma of renal pelvis extensively infiltrating to the renal parenchyma. The patient is alive with no recurrence or metastasis for eight months after operation. Statistical analysis was made on 136 cases of squamous cell carcinoma of renal pelvis reported in the Japanese literature including our case, and this disease is also briefly reviewed. PMID- 3329457 TI - [A case of left inferior vena cava discovered by chance at nephrectomy for renal transplantation]. AB - A case of left inferior vena cava, in a 35-year-old woman, discovered by chance at nephrectomy for renal transplantation is reported. She was admitted to our hospital as a donor of the kidney to her son. She had no remarkable physical signs on chest or abdomen. All laboratory tests were within normal limits. Intravenous pyelogram showed no major abnormality except for the lower position of left kidney than right one. Abdominal aortogram and selective renal arteriogram revealed no abnormality. Bilateral renal arteries were single. Left nephrectomy for transplantation was performed on April 13, 1983. In this operation the left sided inferior vena cava was discovered by chance. Inferior vena cavography was taken postoperatively. It showed the left sided inferior vena cava, type C. Knowledge of the abnormalities of the left renal vein and inferior vena cava is of surgical importance for the urologist when renal transplantation is being considered. PMID- 3329458 TI - [A case of ureteral polyp in childhood]. AB - A case of ureteral polyp in a 7-year-old boy with the chief complaint of left flank pain was reported. The excretory urogram and retrograde pyelography showed left hydronephrosis and a filling defect at the pelvic-ureteric junction. Partial resection of the ureter containing the lesion and Anderson-Hynes pyeloplasty were performed. The pathological diagnosis was benign polyp of the ureter. Convalescence was uneventful and excretory urogram showed improvement of the hydronephrosis. Along with our case, 19 cases of ureteral polyp in childhood are briefly discussed. PMID- 3329460 TI - [The cost of nosocomial infection and its prevention. Projection and limitations of an economic analysis]. PMID- 3329459 TI - [A case of retrovesical abscess due to Crohn's disease]. AB - A 29-year-old man was admitted with pain on urination and high grade fever-up. Mass was palpated above the right lobe of prostate. Cystoscopy revealed an edematous region in the upward to the right ureteral orifice. CT revealed the retrovesical mass in the same region. The surgical specimen obtained by transurethral resection showed severe inflammatory changes, but no malignancy was found. Antimicrobial chemotherapy had been continued, but the mass did not disappear on palpation and computed tomography and cystoscopy revealed pus discharge from the center of the edematous region was found. An operation was performed under the diagnosis of retrovesical abscess. The terminal ileum had formed adhesion to the posterior bladder wall. Segmental resection of the ileum and partial resection of involved segment of the bladder were performed. The pathological diagnosis was Crohn's disease. Inflammation of ileum seemed to infiltrate the bladder wall and formed an abscess. After the operation symptoms disappeared. PMID- 3329462 TI - Development of adipose tissues. AB - Studies on the development of brown and white adipose tissues and their relationship to ordinary connective tissue are the subject of the present review, which is updated to the fall of 1985. Primordial entities described as "primitive organs" have been noted at sites of adipose tissue development by numerous investigators. These "primitive organs" are clearly delineated from surrounding connective tissue and possess a well-defined vascular network in the interstices of which cellular organization takes place. The precursor cells of brown and white adipocytes appear to acquire their distinctive cytogenetic properties at a very early stage in the embryo. These progenitor cells temporarily exhibit structural similarities to fibroblasts and endothelial cells. This resemblance has led to speculation that fibroblasts and/or endothelial cells may be ancestral to adipocytes. However, recent in vivo and in vitro observations suggest that the brown adipose precursor cell is morphogenetically distinct from the white adipose precursor cell on one hand, and from fibroblasts and endothelial cells on the other. In vitro studies have also shown that the pericytic elements present in both brown and white adipose tissue depots in the adult are quiescent precursor cells that may be recruited under certain circumstances. Areas for further inquiry by means of recently developed techniques are indicated. PMID- 3329461 TI - [Olfactory neuroblastoma. Review of the Spanish literature and presentation of 2 cases]. PMID- 3329464 TI - [Contributions and difficulties of the social approach in psychiatry: apropos of the American forces in Vietnam and veterans]. AB - The high frequency of the psychiatric manifestations ascertained among american Vietnam veterans contrasts with the low incidence observed during the conflict, at least initially. That one increased from 1969: at the time of the military stalemate and of the progressive withdrawing, which were accompanied with a support of these post-adolescents by their groups and by an unconcerned or divided national opinion, still weaker than previously, on one hand; at the occasion of the spread of drugs, on the other hand. If we only consider the latters, their large availability and the often compensating function which they exerted concurred with an accentuation then observed in the United States. Among others ones, this example shows the difficulties encountered in order to discriminate the different variables, particularly social, which interfere. It is necessary to avoid the danger of generalizations based on small samples, not comparable at all times. PMID- 3329463 TI - Coordinated three-dimensional reconstruction from serial sections at macroscopic and microscopic levels of resolution: the human heart. AB - This report describes procedures we have developed for obtaining correlated quantitative structural information at two very different levels of resolution. Accurate reconstructions of entire organs and samples of tissue within organs were produced in correct scalar and topographical relationship using computer assisted techniques. A specially designed sectioning apparatus, a macrovibratome, was used to section serially the ventricles of the human heart macroscopically. Photographs were taken of every slice. A tissue block excised from a slice at a specified locus in the left ventricular wall was embedded in plastic; serial-3 micron sections were cut in each of two orthogonal orientations. Photomicrographs were taken by semi-automated microscopy. Images of both macroscopic and microscopic sections were projected onto a bitpad and manually digitized. The resulting tables of x-, y-, and z-coordinates were reassembled on a VAX 11/750 computer, then transferred to a high-performance graphics workstation and displayed as three-dimensional images. Microscopic images were shown in the correct reference frame with respect to the macroscopic (parent) structure. PMID- 3329465 TI - Phylogeny of luteinizing hormone-releasing hormone systems in protochordates and vertebrates. PMID- 3329466 TI - The nervus terminalis in the mouse: light and electron microscopic immunocytochemical studies. AB - The distribution of gonadotropin-releasing hormone (GnRH)-containing neurons and fibers in the olfactory bulb was studied with light and electron microscopic immunohistochemistry in combination with retrograde transport of "True Blue" and horseradish peroxidase and lesion experiments. GnRH-positive neurons are found in the septal roots of the nervus terminalis, in the ganglion terminale, intrafascicularly throughout the nervus terminalis, in a dorso-ventral band in the caudal olfactory bulb, in various layers of the main and accessory olfactory bulb, and in the basal aspects of the nasal epithelium. Electron microscopic studies show that the nerve fibers in the nervus terminalis are not myelinated and are not surrounded by Schwann cell sheaths. In the ganglion terminale, "smooth" GnRH neurons are seen in juxtaposition to immunonegative neurons. Occasionally, axosomatic specializations are found in the ganglion terminale, but such synaptic contacts are not seen intrafascicularly in the nervus terminalis. Retrograde transport studies indicate that certain GnRH neurons in the septal roots of the nervus terminalis were linked to the amygdala. In addition, a subpopulation of nervus terminalis-related GnRH neurons has access to fenestrated capillaries whereas other GnRH neurons terminate at the nasal epithelium. Lesions of the nervus terminalis caudal to the ganglion terminale result in sprouting of GnRH fibers at both sites of the knife cut. The results suggest that GnRH in the olfactory system of the mouse can influence a variety of target sites either via the blood stream, via the external cerebrospinal fluid or via synaptic/asynaptic contacts with, for example, the receptor cells in the nasal mucosa. PMID- 3329467 TI - The terminal nerve in odontocete cetaceans. PMID- 3329468 TI - The immunocytochemical localization of luteinizing hormone-releasing hormone in the brain of the gray short-tailed opossum (Monodelphis domestica). PMID- 3329469 TI - Luteinizing hormone-releasing hormone in the vomeronasal system and terminal nerve of the hamster. PMID- 3329471 TI - Vertebrate gonadotropin-releasing hormones: phylogeny and structure-function relationships. PMID- 3329470 TI - The chemistry of vomeronasally detected pheromones: characterization of an aphrodisiac protein. PMID- 3329472 TI - Innervation of the cerebral circulation. PMID- 3329473 TI - The involvement of nerve terminals in the paraganglionic chemoreceptor system. PMID- 3329475 TI - Immunochemical studies of the location of luteinizing hormone-releasing hormone neurons in the nervus terminalis of the mouse. PMID- 3329474 TI - Studies on the terminal nerve and its central connections in goldfish. PMID- 3329476 TI - Reproductive biology of the terminal nerve (nucleus olfactoretinalis) and other LHRH pathways in teleost fishes. PMID- 3329477 TI - Functional-anatomical studies on the terminal nerve projection to the retina of bony fishes. AB - We have explored the structure and actions of terminal nerve (TN) fibers in the teleostean retina, the most accessible of TN projections. Using immunocytochemistry we have shown that the goldfish TN contains neuropeptides related to the molluscan cardioexcitatory peptide (FMRFamide) as well as luteinizing hormone-releasing hormone (LHRH). Retinal TN terminals were found upon major dendrites in the distal inner plexiform layer and neuronal cell bodies in the amacrine cell layer. Electron-microscopic double-labeling revealed TN terminals applied to the surface of [3H]-dopamine-, glycine-, and gamma aminobutyric acid (GABA)-accumulating cells. Synthetic LHRH and FMRFamide at less than 1 microM modified spontaneous and light-evoked activity of ganglion cells in isolated superfused goldfish retina, especially during the active breeding season. Salmon(I)-LHRH was 10-30 times as potent as mammalian LHRH and caused rapid, prolonged desensitization. We conclude that LHRH- and FMRFamide-like peptides may be released by retinal TN endings, probably in concert with reproductive activity, and that they act independently through horizontal and/or amacrine cell pathways to modify visual information processing in the retina. PMID- 3329478 TI - [Comparison of the antibiotics most commonly used in dental practice]. PMID- 3329479 TI - [Antibiotic therapy in odontostomatology: various considerations]. PMID- 3329482 TI - [From the cosmetic art to cosmetology]. PMID- 3329480 TI - [Risks deriving from the use of mercury in dental practice]. PMID- 3329481 TI - [Miocamycin in pediatrics. Results of multicenter study in Piedmont and Valle d'Aosta]. AB - A multicenter clinical trial has been fulfilled by 18 Paediatric Hospital Centers in the regions of Piedmont and Aosta Valley, on 139 cases, concerning the use of a new macrolide, miocamycin, in the therapy of various infective diseases, such as upper and lower respiratory tract infections, ear and nose, throat, teeth affections, minor surgery, some contagious diseases. The results of this trial show a good effectiveness of the drug, consisting in a rapid disappearance of the clinical symptoms, a high degree of systemic and gastroenteric tolerability, and very poor side effects. PMID- 3329484 TI - [The pellagra that hit the Canavese between the 1700's and 1800's in the writings of various Canavese physicians]. PMID- 3329485 TI - [Books on Piedmont medicine of the 1600's in the Simeom Collection of the Historical Archives of the City of Turin]. PMID- 3329486 TI - [Combined analysis by ultrasonography and scintigraphy of a tablet along the digestive tract. Preliminary study with 4 cases]. PMID- 3329483 TI - [Electrotherapy, between the 1700's and 1800's, in the works of Carlo Stefano Giulio, Francesco Rossi and Giuseppe Berruti]. PMID- 3329487 TI - [Radioclinical aspects of stress fractures (or Pauzat's disease) of the femoral neck]. PMID- 3329488 TI - [Biological foundations of dyslexia. A review]. AB - This is a review that summarizes the work done in our laboratory during the last three years. We have studied four dyslexic brains. They all bear a symmetric anatomical pattern in a structure closely related to the language areas (planum temporale), which is more commonly asymmetric in normal brains. In addition, their microscopic examination shows numerous ectopias and dysplasias in the cerebral cortex. The high incidence of immune disease in dyslexics and their families suggests a more general developmental problem in developmental dyslexia. The hypothesis is raised that fetal effects of testosterone are involved in regulating neurological as well as immunological development, whereby abnormally high testosterone activity would produce a twofold deficit. Finally, strains of immune-defective mice have been found that bear the same cortical abnormalities as seen in the dyslexic brains previously studied. The immune-defective mouse may prove to be an excellent model for the study of the neuropathological basis of developmental dyslexia. PMID- 3329489 TI - Recent burns of the hand. Early excision-graft versus conventional treatment. A retrospective study during two years. AB - Early excision-graft of burned hands seems to have totally superseded the conventional method of progressive detorsion often with late grafting. Does this treatment merit acceptance under these conditions? Do the theoretical advantages of aggressive methods counter-balance the primary difficulty of diagnosing the initial depth of burn? Are these fewer difficulties and risks in early excision graft than in the slower methods? Can we ascribe the failure of conventional method to a poor technical realisation? Following a short summary of the principles of the two methods, we attempt to answer these questions by a retrospective study comparing identical series of patients. We have begun a prospective randomized trial and present the preliminary results here. PMID- 3329490 TI - [Boutonniere deformity]. AB - This paper was presented at the 1986 Congress of the GEM, as a teaching conference on treatment of the boutonniere deformity, based on the experience of the Nancy Hand Unit. The results of early treatment namely prevention of deformities and stiffness, are in most cases satisfactory, in contrast with late surgical correction which necessitates extensive exposure and tenolysis, and complicated repairs. Conservative rehabilitation and dynamic splinting should always precede, prepare and facilitate late operations, and sometimes avoids any surgery. PMID- 3329491 TI - Resin corrosion cast in experimental evaluation of femoral microanastomosis. AB - In order to obtain more information about the site of microvascular anastomosis, the authors used the methylmethacrylate resin corrosion casts. 80 microvascular anastomoses were performed in Wistar albino rats and divided into two groups: in the Group 1 (40 anastomoses), the resin was injected into the vessel whereas in Group 2, the tissues were prepared without injecting resin. Both groups were compared under the scanning electron microscope (SEM). The SEM preparation was easier in the Group 1 and the artefacts were significantly reduced. The anastomotic site was better appreciated in Group 1 in three-dimensional views. The resin corrosion cast is a promising technique for the evaluation of the microvascular anastomosis. PMID- 3329492 TI - [Classification and heterogeneity of hyperphenylalaninemias linked to a phenylalanine hydroxylase deficiency]. PMID- 3329493 TI - [Hyperphenylalaninemias. The Canadian and Quebec experience]. PMID- 3329494 TI - [Definition and nomenclature of hypothyroidism in children]. PMID- 3329495 TI - [Critical analysis of the method of screening congenital hypothyroidism in France]. PMID- 3329496 TI - [Neonatal screening of hypothyroidism. Methods of confirming the diagnosis by the analysis of free hormones]. PMID- 3329497 TI - [Ultrasonics in the etiologic diagnosis of congenital hypothyroidism]. PMID- 3329498 TI - [Transient anomalies of thyroid function in the newborn infant]. PMID- 3329501 TI - [Neonatal screening of mucoviscidosis]. PMID- 3329500 TI - [Autoimmunity and congenital hypothyroidism]. PMID- 3329499 TI - [Congenital hypothyroidism. Elements of prognosis and bone maturation]. PMID- 3329502 TI - [Reflections on the neonatal screening of mucoviscidosis]. PMID- 3329503 TI - [Neonatal screening of congenital hyperplasia of the adrenal glands caused by 21 hydroxylase deficiency. Realities and perspectives]. PMID- 3329504 TI - Outlook on the cell culture applications. PMID- 3329505 TI - The hemolytic activity of some strains belonging to genus Vibrio. PMID- 3329506 TI - [Myasthenia gravis. Clinical and therapeutic evaluation of 55 cases]. AB - It is reported the study of 55 myasthenia gravis cases, with a review of the symptoms and signals, comparing initial symptoms ant those found at the time of the first evaluation. The mean age of the patients was 31.05 +/- 18.46 and the mean time of follow-up 5.88 +/- 5.47 years. Also the results of the diagnostic tests is reported, as well as the results of the treatment. The patients were treated with anticholinesterasics, corticosteroids, azathioprine, plasma-exchange and thymectomy. A statistical analysis with the chi-square test was unable to show a difference between the above procedures, regarding the definitive resolution of the disease. From the 55 cases, 9 (16.6%) had total remission, 41 (74.5%) remained with symptoms and need some kind of treatment, and 5 (9.09%) died (three patients with thymoma, one patient with congenital myasthenia gravis, severe kyphoscoliosis and pulmonary restriction, and one patient during the thymectomy procedure). It was found a relation between the signs of respiratory insufficiency, myasthenic crisis and thymoma only in the group of patients who died. A review about the diagnostic methods and treatment in the current days is made. PMID- 3329507 TI - [Stereotaxic radiosurgery in the treatment of cerebral arteriovenous malformations]. AB - Since March 1983 we are attempting for the first time in Brazil to develop improvements on stereotactic radiosurgery techniques. We have been using the multifocal irradiation method attaching to this purpose the Barcia IV stereotactic frame to a 4 MV linear accelerator. We show details about the centralisation technique and the security patterns in our system. From October 1983 to November 1986, 25 patients with arteriovenous malformations of the brain were submitted to a radiosurgery treatment in our service. Good results obtained on the follow-up from one to three years are analysed. PMID- 3329509 TI - Hyaluronic acid and hyaluronidase activity in gingival exudate from sites of acute ulcerative gingivitis in man. AB - Gingival exudates from sites of acute ulcerative gingivitis (AUG) and chronic gingivitis (CG) in adults were investigated by cellulose-acetate electrophoresis for the hyaluronic acid (HA) content and assayed for the levels of HA-degrading enzymes. HA was the only glycosaminoglycan (GAG) in gingival exudate from CG sites. HA was not detected at untreated AUG sites but was evident, at increasing levels, after two and seven days of effective antibacterial treatment. In AUG exudates, the total HA-degrading enzyme activity, of bacterial origin, decreased to approx. 30 and 10 per cent of the high initial levels after two and seven days of treatment respectively, to that level found at sites of CG. The specific activity of HA-degrading enzyme of lysosomal origin was low initially and increased with treatment to a level comparable to CG. The notable absence of HA from gingival exudate from sites of untreated AUG thus appears to result from the increased levels of bacterial hyaluronidase. Electrophoresis of gingival exudate may be an indirect method of monitoring the rate of response of AUG to different antibacterial treatments. PMID- 3329508 TI - [Neurocryptococcosis in childhood. Report of 3 cases in the 1st decade of life]. AB - The authors report three cases of central nervous system cryptococcosis in children in the first decade of life, from Rio Grande do Sul State, Brazil. Diagnosis was supported by demonstration of Cryptococcus neoformans with India ink preparations of the spinal fluid and Sabouraud's media culture. Clinical presentation included acute, subacute and chronic forms. Increased intracranial pressure and hydrocephalus were the complications during the course of the disease, and a ventriculoperitoneal shunt was used in one case. Undernutrition was associated with all cases and tubercle bacillus infection with one. Specific therapy was administered to the three patients. One patient was cured and the other two died. PMID- 3329511 TI - Incest: what do we really know about it? AB - The literature on incest is reviewed. Current knowledge rests on a very insecure scientific basis and has been mainly derived from small, highly selected clinical series. Recently, some important epidemiological studies of general populations have been reported, but the results of prevalence are inconsistent. Overall, however, it appears that incest, when defined in terms of sexual intercourse, occurs in less than 1% of the population, but other forms of intrafamilial sexual activity may affect 10% of females before they are 16 years of age. Some children are more at risk than others. Because information has generally been derived from court or treatment samples, we are unclear about the long-term effects of incest experiences but, overall, the impression is that incest has markedly adverse effects, especially if it is accompanied by violence and threats and is directed, as it usually is, at the young pre-pubescent child. PMID- 3329510 TI - Benign schwannoma of the pterygopalatine fossa with intracranial extension: a case report. AB - The authors present a rare case of benign schwannoma arising in the pterygopalatine fossa. The patient, an 18-year-old female, initially noticed blurring of her left eye but later, sudden loss of her left vision occurred. Radiological and computed tomographic studies outlined a mass occupying the left pterygopalatine fossa, which extended into the middle cranial fossa, the maxillary, ethmoid and sphenoid sinuses and the orbit. The histology of a transantral biopsy was reported as a benign schwannoma. The tumor was successfully removed by a transmaxillary approach. The eye symptoms disappeared four weeks following surgery. The nerve of origin of the tumor was not identified. The authors posturate that erosion of the skull base with mild to moderate extension into the middle cranial fossa, does not appear to be a contraindication for excising a schwannoma by the transmaxillary approach in this area. PMID- 3329512 TI - The pharmacological treatment of tricyclic-resistant depression: review and management guidelines. AB - Despite the introduction of a wide range of antidepressant drugs since the late 1950s, approximately 30-50% of depressed subjects do not respond to these agents. Various treatment strategies, both pharmacological and non-pharmacological, have been proposed for treatment-resistant depression. This paper critically reviews the studies of single and combined pharmacological treatments for tricyclic resistant patients, with a particular discussion of lithium augmentation. The major inadequacies of these studies have been the frequent lack of definitions of treatment resistance, the heterogeneity of the depressed samples, and the infrequent use of double-blind, placebo-controlled designs. Two central issues, definition of treatment resistance and clinical predictors of response to pharmacological treatments, are discussed in detail. Finally, a suggested guideline for the management of tricyclic-resistant depression is proposed. PMID- 3329513 TI - Sex differences in neuroticism: a quantitative synthesis of published research. AB - The personality trait of neuroticism is thought to be an important risk factor for depression. To ascertain the possible role of neuroticism in producing sex differences in depression, a meta-analysis was carried out on published studies reporting sex- and age-specific norms for neuroticism inventories. A general sex difference was found, with females having higher scores. However, the sex difference was greater in young and middle-aged adults than in children or the very elderly. This age trend in sex differences for neuroticism is similar in form to that previously reported for depression, except that the sex difference for depression completely disappeared in the very young and very old, but the sex difference in neuroticism did not. PMID- 3329514 TI - The secret and the self: on a new direction in psychotherapy. AB - This paper briefly describes some principles of a self-psychology, this term being used in a broad sense. As a heuristic device, the theme of evolution of self is woven about the formation of its boundary. Boundary formation is seen to be fostered by therapeutic responses that 'match' inner states. This notion is linked to other means of enhancing a sense of 'innerness'. They include a respect for the distinction between the realms of public and private, a potentiation of the 'ownership' of experience and the use of certain forms of language. Through a consideration of the concept of 'the secret', self-psychology is contrasted with the traditional or ego psychologies. What emerges is a therapeutic approach to personality disorder that resembles important aspects of the work of Kohut and Winnicott, the major contributors to this developing body of theory. PMID- 3329515 TI - Learning and memory impairment with benzhexol. AB - A double-blind trial to determine the effects of a single dose of 2 mg benzhexol on cognitive functioning was undertaken using normal volunteers. Ninety minutes after the drug or placebo was taken, subjects completed a battery of psychological tests designed to measure learning, memory and motor skills. Benzhexol ingestion was associated with significant impairment of short-term memory and slowing of the rate of new learning. PMID- 3329517 TI - [Preliminary results in malaria control by a sporozoite vaccine]. PMID- 3329516 TI - Diuretic and uricosuric effects of traxanox sodium in healthy subjects. Single dose study. AB - A new compound, 9-chloro-5-oxo-7-(1H-tetrazol-5-yl)-5H-[1]-benzopyrano[2,3- b]pyridine sodium salt pentahydrate (traxanox sodium, Y-12141) has been shown to exert uricosuric effect in animal experiments. This study was performed to investigate the pharmacokinetics and pharmacological effects of this compound in healthy subjects by double-blind, cross-over comparison with placebo. The urine volume and urinary electrolytes increased significantly after single oral doses of 120 and 360 mg. Urinary excretion of uric acid tended to increase and serum uric acid decreased significantly. Traxanox sodium did not induce any significant change in blood pressure and pulse rate. These results suggest that traxanox sodium is a useful diuretic agent with uricosuric effect. PMID- 3329518 TI - Iscom--an immunostimulating complex. PMID- 3329519 TI - Angioimmunoblastic lymphadenopathy with dysproteinemia in Thailand. AB - Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a disease of unknown etiology and pathogenesis. It has the features of hyperimmunity and immune deficiency, and its behavior resembles malignant lymphoma. We report a review of 16 patients with AILD seen at Ramathibodi Hospital from 1982 to 1986. Thirteen patients had fever and seven had pruritus and rashes. Lymphadenopathy was found in all 16 cases; generalized in 14 and localized in 2. Hepatomegaly was present in 14 patients while only 7 had splenomegaly. Laboratory findings included autoimmune hemolytic anemia, lymphocytosis and polyclonal hypergammaglobulinemia. Pulmonary involvement was seen in 5 cases, and bone marrow showed the characteristic features of the disease in 9 cases. Two patients went on to develop diffuse lymphocytic, poorly differentiated lymphoma. Fourteen patients were treated with prednisolone initially. Five responded with complete recovery, eight responded with partial recovery, and one died with extensive involvement of the disease. Six of the patients that recovered partially were later treated with cyclophosphamide, vincristine and prednisolone. One patient recovered completely and two partially. Three died from extensive involvement. Two patients with malignant lymphoma were treated by combination chemotherapy. One case went to complete remission while the other died from infection. One patient was lost to follow up before any treatment was started. PMID- 3329520 TI - Fractionation and characterization of urinary filarial antigen in bancroftian filariasis. AB - Urine samples from microfilaraemic patients were concentrated and fractionated by gel chromatography on Ultrogel AcA 44. Four protein fractions labelled as UFA C1, UFA C2, UFA C3 and UFA C4 were tested for filarial antigenicity by sandwich ELISA. UFA C1 and UFA C2 showed antigenic activity. On further analysis by SDS PAGE, UFA C1 and UFA C2 showed antigenic components with MW ranging from 10.4 K to 123 K. UFA C1-1 and UFA C2-2 showed high antigen titre in ELISA. Urinary albumin was observed as a major component in UFA C2. Absorption of albumin from UFA C2 enhanced its antigenic activity considerably. As little as 0.01 pg antigenic protein per test was found to be sufficient for the detection of filarial antibody in ELISA. Biochemical characterization indicated a glycoprotein nature of UFA C2. PMID- 3329521 TI - Immunodiagnosis of snake venom poisoning. AB - Uncertainty as to the species diagnosis remains a serious problem in the management of snake venom poisoning. This is particularly so in areas inhabited by numerous species, the venoms of which elicit similar pharmacological effects and clinical symptoms and against which para-specific cross-neutralizing antivenom is not available. Attempts have been made to eliminate some of this ambiguity through the development of various immunodiagnostic tests. Tests based on ELISA are sensitive, specific and even quantitative and adaptable to field application. In the development of diagnostic tests for use in developing countries, however, practical consideration must be given to speed, cost, simplicity in terms of equipment and expertise, and stability to the climate and storage conditions. This may dictate further modification or selection of more suitable alternative methodologies. Furthermore, the test may have to allow more flexibility in accommodating local species distributions and to address probable complications of heterophile antibodies in test samples from rural people. PMID- 3329522 TI - A new approach to chemotherapy based on molecular biology and nucleic acid chemistry: Matagen (masking tape for gene expression). AB - The nucleotide sequences of genes contain information which can potentially be used to understand gene function and thus the biological properties of living organisms. This information can also be used to develop innovative new strategies for chemotherapy employing sequence-specific non-ionic oligonucleoside methylphosphonates. These oligonucleotide analogs, termed Matagen (an acronym for masking tape for gene expression), have the following properties: (1) the negatively charged phosphodiester linkage normally found in nucleic acids is replaced with a non-charged methylphosphonate group which confers increased lipophilicity to the oligomer; (2) the oligomers form stable hydrogen-bonded complexes with complementary nucleic acid sequences and retain the fidelity of Watson-Crick base pairing; (3) the lipophilic oligomers cross the cell membrane and also enter various organs of the body; and (4) the methylphosphonate backbone is inherently resistant to nuclease hydrolysis and thus oligomers are taken up intact from cell culture media and remain stable within the cellular environment. Two general strategies are used to block gene expression by Matagens at the mRNA level in mammalian cells. In the first approach, Matagens complementary to specific sites such as the initiation codon region are used to block translation of mRNA. Thus Matagens specifically inhibit translation of rabbit globin mRNA in cell-free systems and rabbit reticulocytes, and vesicular stomatitis virus protein synthesis, but not cellular protein synthesis, in virus-infected cells. In the second approach, Matagens complementary to splice junctions of precursor mRNAs are used to inhibit splicing. For example, a Matagen complementary to the donor splice junction of simian virus 40 (SV40) large T-antigen mRNA inhibits T antigen synthesis in SV40-infected cells, and a Matagen complementary to the acceptor splice junction of herpes simplex virus (HSV) immediate early pre-mRNA 4 + 5 inhibits HSV replication in virus-infected cells. Two new types of Matagen, one derivatized with the photoactivatable cross-linking group psoralen and the other derivatized with a hydroxyl radical-producing group, EDTA-Fe(II), have been designed to improve the efficacy of Matagen and to overcome some of the problems inherent in physical binding of Matagens to complementary nucleic acids. The Matagen approach provides a new way to design antiviral and chemotherapeutic agents in a rational manner. It combines nucleic acid chemistry and chemotherapy to form a common basis for drug development as well as to provide fundamental knowledge about organisms and humans. PMID- 3329523 TI - Targeting calmodulin for the development of novel cancer chemotherapeutic agents. AB - The calcium-messenger system is involved in the regulation of cellular proliferation. Alterations in any of the components of this system could lead to states of abnormal cellular proliferation. We have focused our attention on drugs that antagonize the actions of calmodulin, a central calcium regulatory protein. Following purification of calmodulin from normal and malignant cells by preparative polyacrylamide gel electrophoresis, we determined the sensitivity of the molecule to several classes of calmodulin antagonists and found a direct correlation between antagonism of calmodulin and inhibition of cellular viability. Fluphenazine mustard was shown to be an irreversible calmodulin antagonist and an extremely potent inhibitor of leukemic cell growth. Dequalinium and rhodamine-123, drugs selectively accumulated in malignant cells, were found to be potent calmodulin antagonists, and inhibited the growth of C6 astrocytoma cells. Further studies led to the observation that the combination of calmodulin antagonists with bleomycin produced synergistic cell-kill that was related to enhanced DNA damage. The combination of trifluoperazine and bleomycin was safely administered to 19 heavily pre-treated cancer patients, of whom four had excellent clinical responses. These studies suggest that calmodulin might be an important target for the development of new antineoplastic drugs. PMID- 3329524 TI - Therapeutic selectivity of vinca alkaloids: a role for guanosine 5'-triphosphate? AB - Tubulin, the protein subunit of microtubules, is considered a target for antimitotic agents such as colchicine, maytansine and the vinca alkaloids vincristine and vinblastine. Of these agents, only vincristine and vinblastine have been found to have clinical utility for treatment of human neoplastic disease. The basis for therapeutic selectivity was examined in a comprehensive model in which human rhabdomyosarcomas were grown as xenografts in mice. This model has allowed a detailed examination of differences between neoplastic and non-neoplastic tissues with respect to binding, retention and metabolism of vinca alkaloids. Of note is that in tumor tissue, vincristine is tenaciously bound whereas vinblastine is not. In non-neoplastic tissue, retention of both agents is poor. The mechanisms responsible for differential retention between vinca alkaloids and between neoplastic and non-neoplastic tissues were examined. Results suggest that guanosine 5-triphosphate may be implicated in the formation and stability of vinca-tubulin complexes in tissue cytosols. Two models consistent with the data are proposed, and the significance to therapeutic efficacy is discussed. PMID- 3329525 TI - DNA repair, ADP-ribosylation and pyridine nucleotide metabolism as targets for cancer chemotherapy. AB - DNA repair mechanisms serve as useful targets for modulating the cytotoxic and chemotherapeutic effects of many agents whose mechanism of action involves the induction of DNA damage. For example, the modified base O6-methylguanine can inactivate the repair protein O6-alkylguanine alkyltransferase, thereby sensitizing cells to the cytotoxic effects of clinically useful nitrosoureas such as BCNU. Some of the cytotoxic DNA adducts induced by BCNU are repaired by O6 alkylguanine alkyltransferase; thus, inactivation of the protein by O6 methylguanine converts cells that are relatively resistant to BCNU into sensitive cells. Another cellular enzyme, poly(ADP-ribose) polymerase, responds to DNA strand breaks by cleaving its substrate, NAD+, and using the resultant ADP-ribose moieties to synthesize homopolymers of ADP-ribose. The use of agents such as benzamide derivatives to inhibit enzyme function results in the accumulation of DNA strand breaks and potentiates the tumoricidal effects of some DNA strand breaking agents such as bleomycin. Poly(ADP-ribose) polymerase can also affect pyridine nucleotide metabolism in a manner that initiates biochemical alterations leading directly to cell death. Thus, the amount of NAD used in the synthesis of poly(ADP-ribose) is dependent on the number of DNA strand breaks present in the cells. DNA damage can sufficiently activate the enzyme to rapidly consume NAD and consequently deplete ATP levels, resulting in the cessation of all energy dependent functions and cell death. Understanding this biochemical pathway that leads to cell death provides a new basis for modulating chemotherapy. For example, agents such as Tiazofurin and/or 6-aminonicotinamide can each be used to alter pyridine nucleotide metabolism, lower NAD pools and potentiate the cytotoxic effects of other chemotherapeutic agents whose primary target is the induction of DNA damage. PMID- 3329526 TI - Synthesis and ribonucleotide reductase inhibitory activity of analogues of 2,3 dihydro-1H-imidazo[1,2-b]pyrazole (IMPY). AB - A series of derivatives of the ribonucleotide reductase inhibitory anti-tumour agent 2,3-dihydro-1H-imidazo[1,2-b]pyrazole (IMPY), including all the methyl analogues, have been synthesised. IMPY itself caused 50% inhibition of L1210 tumour-derived ribonucleotide reductase at a concentration of 0.39 mM, comparable with enzyme obtained from other sources. The analogues proved to be no better than IMPY, either as inhibitors of this enzyme or of the growth of L1210 cells in vitro. No correlation was apparent between biological activity and position of substitution. PMID- 3329527 TI - Immunological agents in the respiratory tract: their role in homeostasis and immunopathogenesis of some morbid conditions of the airways. AB - Some immunological agents, which are expected to interfere with homeostasis and immunopathogenesis of some morbid conditions of the airways, have been reviewed. Attention was focused on some immunoglobulins (IgG, IgA, IgE) and other immunoeffectors such as alveolar macrophages, eosinophils, lymphocyte subsets, interleukins. Other substances, which prospective relation with immunity has been lately highlighted, were considered as well (fibronectin, neuropeptides). The possible pathological role of these immunoeffectors has been discussed. PMID- 3329528 TI - Double-blind comparison of long acting propranolol and sustained release metoprolol in the treatment of angina pectoris. PMID- 3329529 TI - Intrathoracic complications of acute pancreatitis. AB - Acute pancreatitis has an incidence of approximately 50 cases per million of the United Kingdom population and a mortality of 10-18%. Intrathoracic complications have been implicated as the major factor in 22-29% and a contributing factor in a further 29-39% of all deaths. Sixty per cent of deaths occur in the first week of hospital admission and in these the pleuropulmonary complication rate is 94%. In the survivors there is little residual lung damage and the recovery of the pulmonary function is invariably complete. Knowledge of the pleuropulmonary complications of acute pancreatitis may aid with the identification of high risk groups so that supportive measures (including mechanical ventilation) can be implemented early in the course of the illness. This article reviews the major intrathoracic complications of acute pancreatitis (Fig. 1) under the broad headings of: 1. pleural effusion 2. acute pulmonary dysfunction (a) hypoxaemia without pulmonary infiltrates (b) hypoxaemia with pulmonary infiltrates (including the adult respiratory distress syndrome; ARDS). PMID- 3329530 TI - Oral Fabrol (oral N-acetyl-cysteine) in chronic bronchitis. AB - Five hundred and twenty-six patients suffering from chronic bronchitis were randomized to receive either N-acetylcysteine (NAC) or placebo during a 6-month period. The aim was to compare the number of acute exacerbations in the two groups. General practitioners were asked to enter patients with a diagnosis of chronic bronchitis, based on the MRC criteria. We failed to find any statistically significant difference in the number of exacerbations between the two treatment groups although there was a slight trend towards improvement in the NAC group during the first 3 months of the trial. The tolerability was similar for both treatments. Patients taking NAC showed a reduction in number of days on which they were incapacitated and this result was statistically significant. PMID- 3329531 TI - A controlled trial of nebulized aminoglycoside and oral flucloxacillin versus placebo in the outpatient management of children with cystic fibrosis. AB - Six children with cystic fibrosis who had persistently had Pseudomonas aeruginosa isolated from their respiratory tract, completed a double-blind cross-over comparison of oral flucloxacillin and nebulized aminoglycoside versus double placebo. The patients had higher FEV1 results at the end of the month of active treatment than after the month of placebo. PMID- 3329533 TI - Lipid fluidity and membrane protein dynamics. AB - Membrane fluidity plays an important role in cellular functions. Membrane proteins are mobile in the lipid fluid environment; lateral diffusion of membrane proteins is slower than expected by theory, due to both the effect of protein crowding in the membrane and to constraints from the aqueous matrix. A major aspect of diffusion is in macromolecular associations: reduction of dimensionality for membrane diffusion facilitates collisional encounters, as those concerned with receptor-mediated signal transduction and with electron transfer chains. In mitochondrial electron transfer, diffusional control is prevented by the excess of collisional encounters between fast-diffusing ubiquinone and the respiratory complexes. Another aspect of dynamics of membrane proteins is their conformational flexibility. Lipids may induce the optimal conformation for catalytic activity. Breaks in Arrhenius plots of membrane-bound enzymes may be related to lipid fluidity: the break could occur when a limiting viscosity is reached for catalytic activity. Viscosity can affect protein conformational changes by inhibiting thermal fluctuations to the inner core of the protein molecule. PMID- 3329532 TI - Effect of terbutaline administered from metered dose inhaler (2 mg) and subcutaneously (0.25 mg) on tracheobronchial clearance in mild asthma. AB - Tracheobronchial mucus clearance was measured in nine mild asthmatics, using an objective radioaerosol technique, on 3 separate days at intervals of 1 week. Immediately after radioaerosol inhalation, drug or placebo was administered via subcutaneous injection (SC) plus metered dose inhaler (MDI)--2 puffs. Three randomized treatments were used: saline placebo SC plus 2 mg terbutaline by MDI (1 mg per puff); 0.25 mg terbutaline SC plus placebo (propellants and surfactant only) by MDI; and double placebo. Changes in lung mucociliary clearance showed an inverse relationship to baseline clearance of both proximal and distal ciliated airways following inhaled terbutaline, whereas terbutaline SC related inversely only to baseline clearance of the distal ciliated airways. This may reflect the surface concentrations of drug, established by each route. PMID- 3329534 TI - Quantitative energy dispersive X-ray microanalysis of eight elements in pancreatic endocrine and exocrine cells after cryo-fixation. AB - Quantitative X-ray microanalysis of 8 elements was performed on ultrathin, freeze dried sections of islets and pancreas pieces from non-inbred ob/ob-mice. Diffusion of elements was reduced to a minimum by rapidly freezing the tissue samples between nitrogen-cooled polished copper surfaces and avoiding the use of chemical fixatives and stains. The ultrastructural morphology was adequately maintained to allow measurements on secretory granules, mitochondria, cell nuclei, and cytoplasm free of these organelles. The distribution of the various elements between cellular compartments was similar in islet beta-cells and exocrine pancreas cells. However, the insulin secretory granules were outstanding in exhibiting the highest concentrations of zinc and calcium. In comparison with cytoplasm in the beta-cells, the insulin granules accumulated calcium 2-fold and zinc as much as 40-fold. As no correlation could be made for endoplasmic reticulum in the cytoplasmic measurements areas, the true accumulations above cytosol are likely to be even higher. PMID- 3329535 TI - The effects of meal-feeding and the diurnal cycle on lipogenesis in brown adipose tissue of rats. AB - A significant diurnal variation in the rates of lipogenesis in vivo in brown adipose tissue occurred in both virgin and lactating rats. On a meal-feeding regime of either a chow, high-sucrose, or high-lipid diet, there was a very large increase in BAT lipogenesis following the meal. The rates observed after the sucrose meal are the highest so far reported. There was no significant difference in BAT lipogenesis between lactating and virgin rats, contrary to previous reports by others. The pattern of stimulation of BAT lipogenesis by these feeding regimes was different from that for white adipose tissue and liver and was not correlated with plasma insulin levels. PMID- 3329536 TI - Hormone-sensitive lipase in brown adipose tissue: identification and effect of cold exposure. AB - Hormone-sensitive lipase (HSL) in brown adipose tissue from mice was identified through immunoprecipitation with a polyclonal antibody (anti-HSL) towards rat white fat HSL and Western blotting. An 82 kDa polypeptide, slightly smaller than the rat white fat HSL 84 kDa subunit, was detected and its identity as HSL verified by inhibition properties. The HSL concentration per g tissue was several fold higher in the mouse brown adipose tissue than in the rat white adipose tissue, but the specific activities per mg protein were similar. Cold-exposure (4 degrees C) of the mice for 24 h approximately doubled the HSL concentration but this increase parallelled the overall protein increase and did not reflect a specific effect on the HSL. PMID- 3329537 TI - Applications of artificial cells in medicine and biotechnology. AB - This article summarizes those research activities in the area of artificial cells which are related to medicine and biotechnology. This includes the applications of artificial cells in: (1) chronic renal failure, (2) drug poisoning, (3) aluminium and iron removal, (4) fulminant hepatic failure, (5) immunosorbent for direct blood perfusion, (6) enzyme therapy and metabolic function replacement, (7) immobilized cell cultures for Bioartificial Organs, (8) blood substitutes, (9) microencapsulation, (10) biotechnology and other areas. PMID- 3329538 TI - Intraperitoneal immunoglobulin (IG) treatment in prophylaxis of bacterial peritonitis in CAPD. AB - To evaluate peritoneal immunological defences and to find a possible cure for alterations in the mechanism, we studied the capacity of peritoneal dialysis effluent (PDE) to opsonize bacteria and the phagocytic activity of peritoneal macrophages (PM). Subjects were 40 uremic patients followed for a mean period of 36 months and 40 normal women who underwent laparoscopy (Controls). Opsonic capacity for S.epidermidis of undiluted PDE from CAPD patients with low peritonitis occurrence (LPI) proved similar to that of 10% control serum. It was, however, noticeably inferior when patients were of high peritonitis incidence (HPI). In these cases IgG concentration in PDE was lower than in patients of LPI. A significant correlation was revealed between opsonization capacity for bacteria and IgG concentration values in PDE. We found inverse correlation between opsonic capacity of PDE and number of episodes of peritonitis. Phagocytic capacity of PM from CAPD patients was similar to that of control PM when microorganisms were preopsonized by control serum. Intraperitoneal Immunoglobulin treatment raised PDE opsonization capacity and lowered peritonitis incidence in patients of previously HPI, thus demonstrating the importance of abnormal organization in CAPD peritonitis and the possibility of preventing infections by intraperitoneal Immunoglobulin treatment. These prevention results do not occur with intravenous Immunoglobulin treatment. PMID- 3329539 TI - Hemosorption and other efferent methods in medicine. PMID- 3329542 TI - pH measurement in the oesophagus. PMID- 3329541 TI - Recent views on the pathogenesis of gastro-oesophageal reflux disease. AB - The pathogenesis of GORD depends on a mix of factors which vary amongst individual patients. The central issue in the pathogenesis of gastro-oesophageal reflux is understanding of the mechanisms that lead to reflux, since the effects of all other factors depend on this event. Consequently, new information and views about the mechanisms of gastro-oesophageal reflux have been presented in detail. This information suggests that defective lower oesophageal sphincter motility is the most important abnormality that underlies pathological gastro oesophageal reflux. Two major forms of LOS dysfunction have been identified as responsible for pathological gastro-oesophageal reflux in the horizontal position: (1) an excessively frequent rate of occurrence of transient LOS relaxations; and (2) defective basal LOS tone. Both of these dysfunctions appear to arise from abnormal neural control of the LOS, probably by the central nervous system. The effect of these LOS dysfunctions on gastro-oesophageal competence is probably significantly influenced by non-sphincteric factors, the most important of these apparently being hiatus hernia. Though there is currently poor understanding about the ways in which hiatus hernia impairs gastro-oesophageal competence, measurement techniques have now advanced sufficiently to allow significant accrual of knowledge in this field. Once reflux has occurred, the efficiency of oesophageal acid clearance plays a major role in determining the impact of reflux on the oesophageal mucosa. Recent studies have shown that oesophageal acid clearance depends on both effective volume clearance and neutralization by saliva of residual acid in the oesophageal lumen. The efficiency of oesophageal volume clearance of both stimulated and real reflux has not been studied formally in GORD patients, but the high incidence of peristaltic dysfunction in reflux disease suggests that volume clearance will be defective in some patients. The limited information available about salivation in GORD patients suggests that salivary secretion is no different from that of age matched controls, but that there is an age-dependent loss of the salivary response to oesophageal acidification. This impairment of salivary response may produce an age-dependent decline of the efficiency of oesophageal acid clearance. Unusually aggressive refluxate and impaired mucosal resistance to injury have been proposed as significant variables which contribute to pathogenesis of reflux disease. The evidence for these factors is circumstantial and scanty. Their importance has probably been overestimated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3329540 TI - Adsorption of immunologically relevant molecules--its present and future. AB - The development of numerous adsorbents of various types oblige us to define the used terms. Adsorbents functioning on the same principle as that of the binding between antigen and antibody should be designated as specific adsorbents or immunoadsorbents. All other kinds of adsorbing materials act more or less selectively. A review is given concerning investigations about selective adsorbents. The removal of IgG antibodies is possible with adsorbents of the protein A type. Synthetic materials with IgE and IgM binding properties are presented and are under development. The blocking of the complement system by binding certain components and breakdown products can be a worthwhile feature in view of the biocompatibility of adsorbing materials. PMID- 3329543 TI - Barrett's oesophagus or columnar epithelium of the lower oesophagus. PMID- 3329544 TI - Techniques, results and complications of oesophageal dilatation. AB - The scope of therapeutic endoscopy, especially in the context of oesophageal dilatation, has greatly expanded in recent years. In this chapter we have described the currently used wire-guided systems and their dilatation technique. This technique can be used with most dilatation instrumentation now on the market. Perforation, the major risk of dilatation, is now rare (0.22% out of 909 dilatations with Savary-Gilliard bougies). Finally, we have presented the results of our own comparative studies for the Eder-Puestow, Savary Gilliard and Biomed systems and those of other authors for systems with which we have had no experience. In our opinion Savary-Gilliard bougies are the best, not only because of their greater flexibility and progressivity but also because of the improved safety tip of the guide wire. PMID- 3329545 TI - Early and long-term results of antireflux surgery: a critical look. PMID- 3329546 TI - Angina-like chest pain of oesophageal origin. AB - Angina-like chest pain of non-cardiac origin is a major diagnostic and therapeutic problem. The oesophagus is frequently suspected to be the cause of the chest pain in these patients. However, a positive statement for the oesophageal origin of the pain can only be made when during manometry or pH monitoring the familiar pain attack appears to be accompanied by reflux, severe motor disorders or a combination of both. Due to the intermittent nature of the pain this is only rarely the case during short-listing conventional examinations. Provocation tests have been used to induce the familiar chest pain. The Bernstein acid perfusion test and the edrophonium test yield the best results. Prolonged (24-hour) ambulatory recording of intra-oesophageal pressure and pH to increase the chances of recording chest pain concomitantly with an episode of reflux and/or motor disorders appears to be the most sensitive and also the most physiological test. It is the only test that provides reliable information on the underlying mechanism of the pain, especially in patients with the syndrome of irritable oesophagus, thus contributing in establishing the appropriate therapy for these patients. PMID- 3329547 TI - Diagnosis and preoperative staging of oesophageal malignancies. PMID- 3329548 TI - Cultural patterns of drug and alcohol use: an analysis of host and agent in the cultural environment. AB - Applying the public health approach, the author of this article analyses the problems of drug abuse and alcoholism in the context of the interactions between the host (person), drugs and the environment in order to understand better the nature, extent, spread, patterns and associated aspects of these problems. Whenever the problems arising from drug or alcohol use reach a critical level in society there is a tendency to view them as an entirely new and unique phenomenon, although such problems relating to socially accepted substances have already occurred in numerous societies over the past few centuries. Patterns of drug use evolve from the meanings, values, attitudes, beliefs and norms that a society assigns to any particular drug. Cultures differ widely in the psychological and social functions that are assigned to drug use. A drug whose use has been woven into the fabric of a stable society runs less risk of being problematic for that society. Increased drug-related problems in societies around the globe often appear as a result of diffusion, or the spread of a given drug or its mode of administration, from one culture to another. Migration, affluence, urbanization and rapid cultural change also contribute to changes in drug use. Cross-cultural studies of drug problems show that certain social strategies concerning drug use hinder the development of such problems and help to reduce and prevent the abuse of drugs and alcohol, while certain other strategies are liable to add to drug problems. PMID- 3329549 TI - Lack of mutagenicity of tetramethylsuccinonitrile in Salmonella typhimurium TA strains. PMID- 3329550 TI - [On contamination of anaerobic spore-forming bacteria in honey under the Japanese pharmacopoeia]. PMID- 3329551 TI - [On the Japanese pharmacopoeia standard "Insulin Standard (854)"]. PMID- 3329552 TI - [Current aspects of medical deontology in the armed forces]. PMID- 3329553 TI - [Sheehan's syndrome (acute steatosis of the liver in pregnancy). Apropos of 8 cases]. PMID- 3329554 TI - [Man and his urine]. PMID- 3329555 TI - [What happened to Voltaire's brain?]. PMID- 3329556 TI - [Implantology and esthetics]. PMID- 3329557 TI - [Glass ceramic inlays-onlays: toward a new form of restorative dentistry]. PMID- 3329559 TI - [Conventional ceramic onlays: a durable esthetic solution]. PMID- 3329558 TI - [Enameling of teeth using glass ceramic veneers]. PMID- 3329560 TI - [The bonded ceramic veneer: a response to an esthetic problem. 1) Clinical steps. 2) Laboratory steps]. PMID- 3329561 TI - [Ceramic inlays. The Cerestore technic]. PMID- 3329562 TI - [Esthetics in complete denture: from prosthetic teeth to "natural" teeth]. PMID- 3329563 TI - Alterations in tissue antioxidant systems in the spontaneously diabetic (BB Wistar) rat. AB - Tissue antioxidant status in insulin-dependent spontaneously diabetic BB Wistar rats (ISDBB), diabetes-prone nondiabetic littermates (NDLM), and weight-matched non-BB control Wistar rats was investigated in pancreas, heart, and liver, as well as kidney. Pancreatic activities of CuZn-superoxide dismutase and glutathione reductase (GSSG-RD) were higher in ISDBB rats, while catalase (CAT) activities were elevated in both ISDBB and their NDLM compared with control animals. On the other hand, pancreatic reduced glutathione (GSH) levels were decreased in both ISDBB and NDLM rats. Cardiac tissues of ISDBB rats had higher activities of CAT and GSSG-RD and elevated levels of GSH compared with weight matched control rats. Hepatic GSH levels in both ISDBB and their NDLM were lower than those of control rats. ISDBB rats showed higher renal activities of glutathione peroxidase compared with control rats. Our results demonstrate the presence of alterations in tissue antioxidant status in BB Wistar rats (both diabetic BB rats and their diabetes-prone nondiabetic littermates). The fact that most of the enzyme changes present in BB rats with overt diabetes paralleled those we have previously reported in rats with uncontrolled streptozotocin induced diabetes and the fact that the latter alterations were corrected with insulin therapy suggest that the alterations in diabetic BB rats were probably related to suboptimal insulin therapy. The significance of the alterations in antioxidant status seen in the nondiabetic BB animals is as yet unknown. PMID- 3329564 TI - Excitation of rat hippocampal neurones by the stereoisomers of cis- and trans-1 amino-1,3-cyclopentane dicarboxylate. AB - Intracellular recordings were obtained from rat hippocampal neurons during the microiontophoretic ejection of the stereoisomers of cis- and trans-1-amino-1,3 cyclopentane dicarboxylate into the dendritic region (stratum radiatum) of the impaled cells. L-(+)-cis-1-Amino-1,3-cyclopentane dicarboxylate, D(+)-trans-1 amino-1,3-cyclopentane dicarboxylate, and L-(-)-trans-1-amino-1,3-cyclopentane dicarboxylate all evoked patterns of excitation resembling that elicited by kainate. All of these responses were unaffected by D-(-)-2-amino-5 phosphonovalerate but were antagonized at comparable currents by kynurenate. The excitation produced by D-(-)-cis-1-amino-1,3-cyclopentane dicarboxylate was similar to that evoked by N-methyl-D-aspartate. At low ejection currents a slow depolarization triggered rhythmic burst firing, each burst consisting of a depolarizing shift in membrane potential upon which were superimposed four to five action potentials. These responses were antagonized both by D-(-)-2-amino-5 phosphonovalerate and by kynurenate. The results are discussed with respect to the conformational requirements considered to be necessary for interaction at the kainate and N-methyl-D-aspartate receptors on CA1 pyramidal neurones. It is important to note that the isopropylene side chain of kainate is absent from the 1-amino-1-3-cyclopentane dicarboxylate molecule. PMID- 3329565 TI - Ultrastructural study of the effect of insulin dosage on the myocardium of spontaneously diabetic BB rats. AB - Cardiac ultrastructure was studied in spontaneously diabetic BB rats maintained on two different regimens of insulin daily. For 3 months from the onset of overt diabetes, one diabetic group was well controlled with daily subcutaneous administration of sufficient insulin to prevent glycosuria (9.0-13.0 U/kg). Approximately half of this dose (4.5 U/kg) of insulin was given daily to a second group of diabetic rats. Normal Wistar rats and nondiabetic BB rats were used as controls. Blood glucose values were three- to four-fold higher with respect to these controls in the diabetic BB rats receiving the smaller dose of insulin but were significantly lower than controls in diabetic animals receiving the higher insulin dose. A 30% difference in body weight with respect to the Wistar controls, obvious hyperliposis, and some nerve degeneration were seen in the low dose insulin group of diabetics. Such changes did not occur in the well controlled insulin-treated group. Electron microscopic examination of the left ventricular tissue revealed mild damage in both groups of diabetics consisting of small focal lesions and mild edema along the sarcoplasmic reticulum and sometimes adjacent to the sarcolemma. Thus, insulin treatment, which prevented glycosuria, resulted in normal tissue lipid levels and prevented nerve damage but had little effect on the other diabetes-induced ultrastructural alterations in the myocardium of these rats. PMID- 3329566 TI - Effect of exercise training on insulin binding and glucose metabolism in mouse soleus muscle. AB - Training stimulates glucose uptake and metabolism by muscles independent of a rise in serum glucose. Whether this increased insulin action is associated with enhanced insulin binding in muscles is unknown. We studied the effect of 6 weeks of treadmill running on insulin binding, uptake of 2-deoxy-D-glucose, glycolysis, and glycogenesis by the soleus muscle of Swiss Webster mice. Training was progressively increased. The in vitro studies using intact soleus preparations were done 48 h after the last exercise bout. Training increased insulin binding, insulin-stimulated uptake of 2-deoxy-D-glucose, and glycogenesis but not glycolysis in the soleus. Our data suggest that the enhanced glucose uptake and metabolism in muscles induced by exercise training are associated with an increase in insulin binding. PMID- 3329567 TI - Renin substrate (angiotensinogen) preparations in the determination of prorenin and renin: evidence for extrarenal plasma prorenin and its renal "convertase". AB - Standard methods for determining prorenin-renin concentrations in plasma (PRC) and other tissues require the addition of exogenous renin substrate (angiotensinogen) to improve the kinetics of the renin reaction. We studied the effects of substrate prepared from normal human plasma fraction Cohn IV-4, or from nephrectomized (2NX) sheep plasma, on PRC of normal and 2NX human plasmas before and after prorenin activation by acid, cold, and trypsin, and compared the results with plasma renin activities (PRA, no added substrate). Plasmas from 2NX men exhibited negligible basal PRA, indicating that very little, if any, renin had been formed from the extrarenal prorenin they contained, and suggesting the lack of an endogenous prorenin activating mechanism, or "convertase," of probable renal origin. Prorenin was demonstrable by tryptic activation, more than by acid or cold, at up to about 30% of normal. Addition of Cohn IV-4 substrate to 2NX plasma unexpectedly produced (i) a basal PRC value higher than in normal plasma, (ii) total renin values after activation by acid, cold, and trypsin that were much closer to normal values than reflected by PRA methodology, without a commensurate increase (if anything a decrease) in prorenin as a percentage of total renin estimated by all activation methods, and (iii) substantial equalization of activation effects such that trypsin was no longer more effective than acid and cold (and this was also noted with normal plasma). The skewing effect of adding Cohn IV-4 substrate on the PRC of 2NX plasma was much greater than in normal plasma, even though 2NX plasma already had an above normal level of endogenous substrate and should have been influenced less. Enhancement of PRC was very pronounced even when Cohn IV-4 was added to make up only 9% of total (endogenous + exogenous) substrate in the incubation system, suggesting that it was not the added substrate but a renin-generating contaminant that inflated the PRC. Such inflation could be blocked by adding protease inhibitors, suggesting that the responsible protease(s) acted as a prorenin "convertase" that generated new renin from renal and (or) extrarenal prorenin contributed by the added substrate, as well as by the plasma being assayed. One component of convertase could be kallikrein, which was identified by chromogenic assay, the importance of which relative to total convertase activity is unknown.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3329568 TI - The 1986 Borden award lecture. The role of the kidney in amino acid metabolism and nutrition. AB - Measurement of the arteriovenous differences for free amino acids across rat kidney reveals that glycine and citrulline are removed and serine and arginine are added to the circulation. In addition, glutamine is taken up in large quantities by kidneys of animals that need to excrete large quantities of acid (e.g., diabetic animals, NH4Cl-fed animals, and animals fed a high protein diet). Glutamine is the major precursor of urinary ammonia and thus renal glutamine metabolism plays a key role in acid-base homeostasis. This process occurs primarily in the cells of the convoluted proximal tubule. Glutamine carbon is converted to glucose in acidotic rats and is totally oxidized in dogs. Regulation of glutamine metabolism occurs at two levels: acute regulation and chronic regulation. Acute regulation is, in part, mediated through a fall in intracellular [H+]. This activates alpha-ketoglutarate dehydrogenase and, ultimately, glutaminase. Chronic regulation involves induction of key enzymes, including, in the rat, glutaminase, glutamate dehydrogenase, and phosphoenolpyruvate carboxykinase. During the acidosis of prolonged starvation, the kidneys' requirement for glutamine must be met from muscle proteolysis and thus becomes a drain on lean body mass. Serine synthesis occurs by two separate pathways: from glycine by the combined actions of the glycine cleavage enzyme and serine hydroxymethyltransferase and from gluconeogenic precursors using the phosphorylated-intermediate pathway. Both pathways are located in the cells of the proximal tubule. Conversion of glycine to serine is ammoniagenic and the activity of the glycine cleavage enzyme is increased in acidosis. The function of serine synthesis by the phosphorylated-intermediate pathway is not apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3329569 TI - Isolation of nonciliated bronchiolar epithelial (Clara) cells and alveolar type II cells from mouse lungs. AB - A method is described for the isolation of alveolar type II cells and nonciliated bronchiolar epithelial (Clara) cells from mouse lungs. Following digestion of lung tissue with Sigma type I protease, viable cells were isolated to 65% purity for type II cells (6.4 +/- 1.5 X 10(5) cells/mouse) and 55-60% purity for Clara cells (2.6 +/- 0.9 X 10(5) cells/mouse). Viability, as assessed by trypan blue exclusion, was routinely greater than 90% in all enriched cell fractions. Although minor mitochondrial changes occurred during isolation, the morphology of the cells showed good preservation, as revealed by electron microscopy. The isolated cells were found to be metabolically active, as indicated by the presence of 7-ethoxycoumarin deethylase (a cytochrome P-450-mediated activity). The highest activity of this enzyme (278 +/- 116 pmol.min-1.mg protein-1) was found in the fraction enriched in Clara cells. The results indicate that this method produces viable cell populations that can be of value in investigations of the cellular distribution of lung metabolism activities. PMID- 3329570 TI - Renal medullary plasma flow rate and reabsorption of salt and water from inner medullary collecting duct. AB - It has been proposed that medullary washout secondary to increased blood flow will limit maximal urine osmolality and reabsorption of salt and water from the inner medullary collecting duct. We have tested this prediction. The function of the inner medullary collecting duct was examined by microcatheterization. Acetylcholine was infused directly into the renal circulation, captopril was infused intravenously, and angiotensin II was infused into the renal circulation in rats which also received captopril. Medullary plasma flow rate, measured by dye-dilution in parallel experiments, was not significantly increased by acetylcholine; it was increased 30% (p less than 0.02) by systemic infusion of captopril, and was returned to control by angiotensin II. Acetylcholine increased both urine flow rate and sodium excretion (p less than 0.01, p less than 0.001, respectively), while captopril increased only sodium excretion (p less than 0.025). Angiotensin II blocked the natriuresis due to captopril. None of the treatments altered urine osmolality (p greater than 0.4 in all cases). Acetylcholine increased the loads of water, sodium, chloride, and total solute delivered to the inner medullary collecting duct. Angiotensin II reduced delivery of water and solutes compared with captopril alone. None of the treatments affected load dependency of reabsorption of water, sodium, chloride, or total solute in the inner medullary collecting duct. We conclude that there is, at most, a weak interaction between medullary blood flow and reabsorption from the inner medullary collecting duct. PMID- 3329571 TI - [A study on the theoretical distribution of the long-incubation tertian malaria in a period of one year]. PMID- 3329572 TI - [Significance of neuroepidemiologic research as viewed from the international distribution pattern of cerebrovascular diseases]. PMID- 3329573 TI - Gene conversion, unequal crossing-over and mispairing at a non-tandem duplication during meiosis of Saccharomyces cerevisiae. AB - We have developed a novel system to examine conversion, exchange and mispairing involving a non-tandem duplication of the ade8 locus in yeast by monitoring the segregation of heterozygous markers between the duplicated sequence. Plasmid Yrp17 carries the yeast selectable markers URA3+ and TRP1+. Yrp17 derivatives with a 4 kb insert carrying ade8-18 were used to clone the mutations trp1-1 and ura3-1 by gap repair. Integrants of the resulting plasmids at the Ade8 locus were crossed to yield diploid hybrids with a non-tandem duplication of Ade8 and heterozygosity for the plasmid markers between the duplicated sequences. 1192 complete, unselected asci were analyzed and 270 exhibiting recombination of the markers contributed by the plasmid were analyzed by Southern transfers to detect changes in plasmid sequences. Twenty-seven tetrads had unequal homologous exchanges and five had unequal sister-chromatid exchanges. Seven tetrads carry an additional copy of the integrated plasmid and ten are missing one. We propose that these two classes represent conversions of the entire 11 kb plasmid, which occur after misalignment and formation of an unpaired loop. Mispairing is a frequent event, and occurs in approximately fifty percent of all meioses. The system described provides a means to determine the meiotic rules of conversion, exchange and pairing for duplicated DNA sequences. PMID- 3329574 TI - A DNA sequence which shows genomic variation in a, alpha and HO strains of Saccharomyces cerevisiae. AB - HindIII digested DNA from various mutant strains of Saccharomyces cerevisiae probed with a 340 bp nucleotide sequence in M13mp8 derived from a mouse liver cDNA clone p1581 showed strong hybridization to a 4.1 kb DNA fragment class. This was limited to the DNA of cells of alpha mating type but the fragments concerned apparently do not originate from chromosome III. The pattern of hybridization was modified in strains carrying the HO gene consistent with there being extra copies of the Bkm-homologous sequence in these cells. Northern analysis of RNA from cells synchronised in various stages of the mitotic and meiotic cell cycle probed with M13mp8/p1581 indicated related transcripts in meiotic cells. PMID- 3329575 TI - Functional in vivo verification in E. coli of promoter activities from the rDNA/tDNA(Val)(GAC) leader region of Zea mays chloroplasts. AB - Restriction fragments containing upstream sequences of the rRNA operon from Zea mays chloroplasts were tested for promoter activity in vivo by insertion into an E. coli promoter-probe vector. The expression of this vector's reporter gene, which codes for alkaline phosphatase, was stimulated more than 1,500-fold upon linkage with the chloroplast rRNA promoter. Site specific mutagenesis of the invariant T of the -10 sequence of this promoter reduced the expression of the reporter gene to 2% of the wild type. This indicates that the chloroplast rRNA promoter, which directs transcriptional initiation 117 bp upstream of the 16S rRNA gene, is also active in the bacterial system. A restriction fragment further upstream containing the gene for tRNA(Val) (GAC) also showed strong promoter activity (29% as compared with the rRNA promoter). This promoter activity probably reflects the chloroplast promoter directing the synthesis of the tRNA(Val) (GAC) primary transcript. Surprisingly, this restriction fragment also displayed promoter activity (13% compared with the rRNA promoter) in reverse orientation. PMID- 3329576 TI - The gene for the 9 kd polypeptide, a possible apoprotein for the iron-sulfur centers A and B of the photosystem I complex, in tobacco chloroplast DNA. AB - The gene for the 9 kd polypeptide (a possible apoprotein for the iron-sulfur centers A and B) of photosystem I has been located in the small single-copy region of tobacco chloroplast DNA. This gene (psaC) was identified by comparing the N-terminal amino acid sequence of the spinach 9 kd polypeptide with the entire sequence of tobacco chloroplast genome. The gene organization is ndhE (101 codons)--263 bp spacer--psaC (81 codons)--94 bp spacer--ndhD (509 codons). Northern blot hybridization revealed that psaC is transcribed in the chloroplasts. The deduced amino acid sequence and secondary structure are presented. The predicted polypeptide is rich in cysteine residues and contains a unique repeated sequence. PMID- 3329578 TI - [Evaluation of the bacteriological diagnosis of lower respiratory tract infections]. PMID- 3329577 TI - [Immunological pathogenesis of pulmonary sarcoidosis]. PMID- 3329580 TI - [Effect of panaxadiol-saponins from ginseng flowers and leaves on DNA synthesis in mouse ascitic reticulocytic sarcoma cells]. PMID- 3329579 TI - [Historical studies on the processing of the fruits of Croton tiglium L.)]. PMID- 3329581 TI - [Advances in the treatment of sick sinus syndrome with traditional Chinese medicine]. PMID- 3329582 TI - [Postoperative astigmatism in cataract. Results of current techniques and perspectives of refractive surgery]. PMID- 3329583 TI - Placing gingival retraction cord. PMID- 3329584 TI - A tribute to Oliver H. Dabiezies, Jr., MD. PMID- 3329585 TI - Pseudomonas ulcers following patching of corneal abrasions associated with contact lens wear. PMID- 3329587 TI - Analysis of corneal thickness and corneal curvature in infants. PMID- 3329586 TI - Microbial keratitis in graft vs. host disease. PMID- 3329588 TI - [The IMZ implant system. Method--clinical aspects--results]. PMID- 3329589 TI - The contribution of William Hunter (1718-1783) to the study of bone and joint disease. AB - William Hunter (1718-1783), the elder of the two famous Hunter brothers, is best known for his remarkable book The Anatomy to the Human Gravid Uterus, and for his contributions to the art of midwifery. However, Hunter also made significant observations in cardiovascular disease, in comparative anatomy, and paleopathology. It is perhaps not sufficiently known that he also made significant contributions in rheumatic disease, and in particular, the anatomy and physiology of cartilage. PMID- 3329590 TI - A six-month follow-up study of a slow-release indomethacin tablet in rheumatic diseases. PMID- 3329591 TI - Comparison of two enzyme-linked immunosorbent assay (EIA) kits with immunofluorescence and isolation in cell culture for detection of respiratory syncytial virus (RSV). AB - Rapid diagnosis of respiratory syncytial virus (RSV) infections is based upon detection of viral antigen in cells obtained from the respiratory tract and usually employs immunofluorescence (IF) reactions or enzyme-linked immunosorbent assays (EIA). The Pathfinder EIA kit (Kallestad Diagnostics) was compared with the Abbott EIA kit by evaluating each against isolation of RSV in cell culture and detection of antigen by IF. The Pathfinder kit identified 116 of 129 culture positive and 72 of 90 culture-negative specimens; the sensitivity was 90 percent and the specificity was 80 percent. The sensitivity of the Abbott EIA test compared to isolation of RSV in cell culture was 91% (115 of 127), and the specificity was 83% (74 of 89). Of 165 specimens evaluated by IF, the Pathfinder kit detected 97 of 105 IF-positive and 45 of 60 IF-negative specimens, giving a sensitivity of 92% and a specificity of 75%. The Abbott EIA compared similarly with IF, showing a sensitivity of 91% (98 of 108) and a specificity (42 of 54) of 78%. Visual reading of the Kallestad test resulted in a sensitivity of 92%, a specificity of 91%, positive predictive value of 95%, and negative predictive value of 86%. The Pathfinder EIA kit compared well with IF and the Abbott EIA for detection of RSV antigen but performed faster than the Abbott test and offers the option of a visual reading. PMID- 3329593 TI - Osseointegrated implants. PMID- 3329592 TI - Rapid identification of Escherichia coli with a fluorogenic beta-glucuronidase assay. AB - We evaluated three fluorogenic methods (MUG; Remel, Lenexa, KS) for the rapid (less than 1 hr) identification of E. coli by detecting beta-glucuronidase activity. The methods included: direct disk inoculation test, tube test, and liquid spot reagent test. Fluorogenic tests were performed on pure cultures of lactose fermenters and compared with identification by Enterotube II (Roche Diagnostics; Nutley, NJ). Organisms yielding disparate results were further analyzed by API 20E (Analytab Products Inc.; Plainview, NY). The tube test was evaluated with isolates subcultured on both MacConkey and blood agars; the direct disk and liquid spot reagent methods were tested with isolates subcultured on blood agar only. All methods were highly specific (greater than 97%). Sensitivity of the beta-glucuronidase tests were method and media dependent, but exceeded 85% in all cases. The direct disk and tube tests also permitted detection of indole formation; results of indole testing, however, contributed little to accurately identifying E. coli. PMID- 3329594 TI - A critical review of EMG-controlled electrical stimulation in paraplegics. AB - This review presents a description and provides a comparative performance evaluation of EMG control vs. other approaches to controlling functional electrical stimulation (FES) in upper-motor-neuron paraplegics to provide them with a certain degree of walking ability with walker support. EMG control is considered in terms of a combination of above-lesion EMG control and below-lesion response-EMG control. The above-lesion EMG is to control the activation of different limb functions involved in standing up and walking via FES. This control is accomplished by analyzing raw surface EMG time-series patterns to discriminate between upper-trunk muscle contraction patterns which, in turn, are correlated with intended lower-limb functions involved in walking, so that natural and instinctive balance changes of paraplegics are reflected and controlled by the patient only above the lesion. The below-lesion response-EMG is the EMG produced in response to the FES pulses at the stimulation sites, for adjusting stimulation levels as needed when contractions weaken due to muscle fatigue. Above-lesion EMG is a stochastic (random-like) signal, being a response to unsynchronized motor-neuron firings, whereas the below-lesion EMG is a deterministic signal responding to synchronized firings that result solely from the FES pulses. The present review discusses the merits and difficulties of EMG control and attempts to give a critical evaluation of patient performance under such control, contrasted to other methods of control, noting that FES-activated walking without adequate and patient-responsive control is of very limited attraction and use to paraplegics. Of the various control methods, only foot- or hand-switch control comes close in overall performance to above-lesion EMG control. Although one cannot categorically prefer EMG control to foot- or hand switch control performance-wise, psychologically, EMG control has the advantage in that concentration is not diverted to the patient's fingers, whereas foot switches are inadequate for patients lacking reasonable natural (non-FES) pelvic thrust control. However, for stimulation-level control, below-lesion response-EMG appears to be the clear answer. It is shown that below-lesion EMG control of stimulation levels can be used independent of above-lesion EMG control. Below lesion EMG control can thus be combined also with hand-switch control or, in case of low level upper-motor-neuron lesions, with pelvis control. Hence, and since FES-activated walking is as good as its control, we conclude that EMG control should be given serious consideration in any FES walking.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3329595 TI - Phonocardiogram signal analysis: a review. AB - Many disease of the heart cause changes in heart sounds and additional murmurs before other signs and symptoms appear. Hence, heart sound analysis by auscultation is the primary test conducted by physicians to assess the condition of the heart. Yet, heart sound analysis by auscultation as well as analysis of the phonocardiogram (PCG) signal have not gained widespread acceptance. This is due mainly to many controversies regarding the genesis of the sounds and the lack of quantitative techniques for reliable analysis of the signal features. The heart sound signal has much more information than can be assessed by the human ear or by visual inspection of the signal tracings on paper as currently practiced. Here, we review the nature of the heart sound signal and the various signal-processing techniques that have been applied to PCG analysis. Some new research directions are also outlined. PMID- 3329597 TI - [The Tourtet framework. Evolution or revolution in removable partial denture?]. PMID- 3329596 TI - A critical review of Compton imaging. AB - This paper reviews the basic aspects, problems, and applications of Compton imaging including those related to nonmedical applications. The physics and technology at the base of this specific methodology are analyzed and the relative differences and merits with respect to other imaging techniques, using ionizing radiations, are reviewed. The basic Compton imaging approaches, i.e., point-by point, line-by-line, and plane-by-plane, are analyzed. Specifically, physical design and technological aspects are reviewed and discussed. Furthermore, the most important clinical applications of the different methods are presented and discussed. Finally, possibilities and applications of the Compton imaging method to other nonmedical fields, as in the case of the important area of object defects recognition, are analyzed and reviewed. PMID- 3329598 TI - [Orodental care in long-term geriatric facilities]. PMID- 3329599 TI - [Impressions with combined reversible hydrocolloid-alginate (hydroalginate)]. PMID- 3329600 TI - [A dangerous error: etching of glass ionomers in the sandwich technic]. PMID- 3329601 TI - [The tooth "worm" in Mesopotamia and ancient Egypt]. PMID- 3329602 TI - [Bacteriological control of water in dental equipment. Study of 9 health units]. PMID- 3329603 TI - [Saint Apollonia, muse of the avant garde or oral medicine meets modern art]. PMID- 3329604 TI - Serological survey of immune response to tetanus toxoid using antitoxin enzyme immunoassay. AB - A method for testing serum tetanus immunoglobulin (TIG) was set up using enzyme immunoassay kit (EIA kit) and prepared by competitive principle in this laboratory. Forty-eight human sera tested by both EIA and toxin neutralization test (NT) in mice were in good agreement. Determination coefficient (r2) of the EIA and NT was 0.922. The lowest detectable dose was 0.1 IU/mL ELISA value. Many authors believe this ELISA value to be a safe protection TIG level. For serological survey of immune response to tetanus toxoid, sera from two groups of subjects were examined. Among 83 subjects, each over 40 years of age, only 47.0% were positive to TIG EIA level. Forty-six subjects with undetectable EIA titres to tetanus toxoid (TT) were immunized against two doses of TT at an interval of four weeks; 44 (95.6%) demonstrated TIG concentration of greater than or equal to 0.2 IU/mL within two weeks to one month following the last dose vaccination. The TIG positive rates of 725 school students' sera, selected by multistage sampling from 2395 specimens, were reported. Those were collected by simple random sampling from geographical area in the North, South, Central, Central Mountain, and East areas of Taiwan according to age groups. They were 80.8%, 65.1%, 56.0%, and 42.0% to the age groups of 0-4, 5-9, 10-14, and 15-17 years respectively. The probabilities of each near by two groups were p less than 0.1; p less than 0.05; p less than 0.05. The differences of positive rates in the last three groups were significant. PMID- 3329605 TI - [Esophageal exclusion by autosuture stapling. Its value in the treatment of spontaneous rupture of the esophagus. Apropos of 5 recent cases]. PMID- 3329606 TI - [Complications and limitations of silicone prostheses in the treatment of neoplastic biliary obstruction. Apropos of 33 personal cases and 500 cases]. PMID- 3329607 TI - [Long-term results of Jean Kunlin's first venous autograft. Apropos of the report of M. J. Descotes et al]. PMID- 3329608 TI - [The centennial of appendicectomy. Apropos of the report of B. Godquin]. PMID- 3329610 TI - [Congenital coarctation of the aorta and kinking deformity of the aortic arch: evaluation of digital subtraction angiography]. PMID- 3329609 TI - [Postoperative jaundice]. PMID- 3329611 TI - [Clinical effect of indapamide on hypertension]. PMID- 3329613 TI - Resin-bonded retainers: a review of the literature (1984-1987). Look where we are today! PMID- 3329612 TI - [Antibacterial and antifungal compounds. VIII. Synthesis and antifungal activity of pyrrol derivatives similar to trichostatin A]. AB - Some p-methylbenzolpyrrole acrylic acids and related compounds were synthesized. The new pyrrole derivatives have structural features in common with trichostatin A, an antifungal antibiotic. The above acids and derivatives were tested against Candida albicans and Candida sp in comparison with miconazole, pyrrolnitrin and amphotericin B and showed very weak antifungal activities. Occasionally some activity was found against a few strains of Candida albicans and against Candida pseudotropicalis. PMID- 3329614 TI - Flaming spear dentist's creation. PMID- 3329615 TI - Stained glass hobby reflects holiday spirit. PMID- 3329616 TI - Counseling makes a difference. PMID- 3329617 TI - [Congenital cystic dilatation of the common bile duct, anomaly of the biliopancreatic junction and cancer of the bile ducts]. AB - The choledochus and pancreatic duct ordinarily enter the duodenum either separately or via a common channel located in the duodenal wall. The usual maximal length of the common channel is approximately 0.5 cm. An anomalous junction of the pancreaticobiliary tract is defined by the presence of an unusually long common channel whose length is 1 cm or longer. During the last 8 years, we studied 9 cases of congenital dilatation of the bile duct. Besides the choledochal cyst, all patients had a common channel which measured 1.5 cm or longer. The mean age of patients (6 females, 3 males) was 36.5 years. Three patients had extrahepatic bile tract carcinoma. One patient, a 51-year old man, had gallbladder carcinoma without stones while the two other patients, a 43-year old woman and a 32-year old man, had carcinoma arising from the wall of the cystic dilatation. These two patients had undergone a simple internal drainage procedure 16 and 8 years before, respectively. Our study suggests that the anomalous junction of the pancreaticobiliary tract, an embryonic anomaly which allows the reflux of pancreatic juice into the bile duct and gallbladder, may be responsible for congenital bile duct dilatation and biliary tract carcinoma. Total excision of the cystic dilatation and the gallbladder with hepaticojejunostomy is the appropriate surgical treatment. PMID- 3329619 TI - [Human pancreatic proteins in normal and pathological states]. PMID- 3329618 TI - [HID-blue alcian (high iron diamine-alcian blue) and the histochemistry of mucins in colonic pathology: 20 years later]. PMID- 3329621 TI - [Colonic Crohn disease disclosed in an acute outbreak: a target population for therapeutic trials?]. PMID- 3329620 TI - [Small-cell anaplastic neuroendocrine carcinoma of the rectum]. AB - A pediculed tumor of the rectum was discovered in a 63 years old man. Within the tumor adenomatous dysplastic proliferation was associated with a neuroendocrine small-cell anaplastic carcinoma. The neuroendocrine nature of the tumor was suspected on conventional optic microscopy and confirmed by a positive Grimelius technique. Specific typical granules were also found on electron microscopy. Immunohistochemical techniques using neurospecific enolase were also positive. Carcinomatous invasion was limited to the submucosa, but the surgical specimen showed that one lymph node was metastatic. Three months later, hepatic metastasis was suspected on physical examination and the patient died of hepatic failure ten months after the discovery of the tumor. Twenty-two similar cases were found in the literature: of these five cases were associated with benign adenomatous lesions. In all cases the patients died of early metastatic diffusion. This tumor raises the problems of diagnosis, terminology, classification and therapy: only aggressive chemotherapy, similar to that applied to the same type of carcinoma in the respiratory tract might improve prognosis. PMID- 3329622 TI - [Significance of time and language in view of the process of medical diagnostic processes. Philosophical methodologic preliminaries]. AB - The understanding of the patient is a prerequisite to philosophical and methodological thinking about the process of medical diagnosis-making. In regard to the philosophical discussion about the recently development of scientific knowledge, the comprehension of the medical object and the conceptions of health and illness has been modified. The human state of illness as a "Zeitgestalt" of intra- and intersubjective disturbances of communication is joined with the individuality and complexity of the subjective experiences of the patient. The modified conceptions of health and illness can help to overcome the division between subject and object, a consequence of Cartesian rationalistic thought. In this way new connections within medical thinking and a new comprehension of medical diagnosis appear. The medical diagnosis-making is simultaneously a process of knowledge to the physician and an instruction for his therapeutical action. The special significance of the medical diagnosis at all is the irreversibility and the temporal openness of the therapeutical action. Medical diagnosis is a form of communication leading to the action of the diagnosis making physician and therefore a inseparable part of the physician-patient relation. The adequate valuation of the multi-dimensionality of the individual pathogenesis (physic, psychic, social) is possible only within this relation. The prediction of critical states presupposes the knowledge of the individual pathogenesis. Of course, such predictions are not completely quantifiable. PMID- 3329623 TI - Metaphase association of mammalian chromosomes. AB - The association behavior of chromosomes bearing nucleolar organizer region (NOR) and (or) C-heterochromatin in metaphase plates was analyzed. Different species with an informative chromosomal localization of NOR and C-heterochromatin were evaluated. Several examples indicate that the well-known metaphase association is not due to NORs or NOR activity per se. Other mechanisms such as ectopic pairing are responsible for the association. These types of pairing seem to be enhanced by the chromatin-decondensing effect of nearby NOR activity. PMID- 3329625 TI - [Growth patterns of different interstitial histiocytes and reticulum cells in lymphocytic lymphoma]. PMID- 3329624 TI - [The relation between resistance of organisms to benzothiazole-rifamycin and the membrane barrier of cells]. PMID- 3329626 TI - The only dentist/mayor in Illinois. Dr. Roger Dettro of Mattoon. PMID- 3329627 TI - Functional role of enzyme conformational changes in metabolism. PMID- 3329629 TI - The interconversion of E. coli tryptophan synthase intermediates is modulated by allosteric interactions. PMID- 3329628 TI - Role of glutathione (GSH) and GSH S-transferases in conjugation of reactive metabolites of chemical carcinogens. PMID- 3329630 TI - Maintenance of pancreatic endocrine cells of the neonatal rat: Part XII- Development of the response by infant rat pancreatic monolayer-cultured B cells. PMID- 3329631 TI - Use of algae, Chlorella vulgaris (Beij) and Scenedesmus quadricauda (Turp) Bre'b and bacterium, Escherichia coli in the treatment of pulp and polyfibre wastewater. PMID- 3329632 TI - Kidney changes in rheumatoid arthritis. PMID- 3329633 TI - Oncocytoma of the kidney: an unusual case with literature review. PMID- 3329634 TI - Statistical methods in cancer research. Volume II--The design and analysis of cohort studies. PMID- 3329635 TI - [Crown-root amputation of mandibular molars]. PMID- 3329636 TI - [Dentin adhesives in crown reconstructions in pedodontics]. PMID- 3329637 TI - [The periodontal probe and periodontal probing]. PMID- 3329638 TI - Renal and urinary tract abnormalities associated with chromosome aberrations. AB - The frequency of malformations of the kidney and urinary tract is much higher in patients with chromosome aberrations than in the general population. Sixty to 100% of "cat-eye" syndrome, 60 to 80% of Turner, 75% of trisomy 8, 33 to 70% of trisomy 18, 50 to 60% of trisomy 13, and over 50% of triploidy and tetraploidy patients may have such abnormalities. Renal and urinary tract malformations should be looked for in all patients with chromosome aberrations. Moreover, a chromosome study is indicated in any fetus with an ultrasonographic evidence of urinary tract abnormality. PMID- 3329639 TI - [Titanium and its applications in dentistry: review of the literature]. PMID- 3329641 TI - [Fixed dentures in periodontopathy]. PMID- 3329642 TI - [Gingivoplasty]. PMID- 3329640 TI - [The contact point in conservative and prosthetic dentistry]. PMID- 3329643 TI - [Sterilization of gutta percha cones: analysis of the literature]. PMID- 3329645 TI - [The etched combination bridge]. PMID- 3329644 TI - [The real or fictitious role of the fiber barrier in the progression of periodontal disease]. PMID- 3329646 TI - [Aspects of removable dentures in periodontopathy]. PMID- 3329648 TI - [A method for electron microscopic observation of human leproma]. PMID- 3329647 TI - Characterization of genotypic and phenotypic variation in plaque-purified strains of HzSNPV Elkar isolate. AB - Twenty plaque-purified strains of Heliothis zea S-type nuclear polyhedrosis virus (HzSNPV) were characterized based upon restriction endonuclease digests of viral DNAs, structural protein profiles, and larval melanization response. Each of the 20 strains had a unique genotype. Genomic heterogeneity between strains was localized to 4 regions of the HzSNPV genome. Differences in protein profiles of occluded virus were noted for each strain relative to the wild-type isolate. The strains were separated into 3 groups based upon differences in relative virulence and rate of larval melanization upon death. There was no correlation between differences in pathology and specific alterations in either genotype or structural proteins. The genotype of strain HzS-15 was extensively characterized. Physical maps were constructed for the HzS-15 strain and all of the plaque purified strains. PMID- 3329649 TI - Spontaneous termination and initiation of ventricular fibrillation as a function of heart size, age, autonomic autoregulation, and drugs: a comparative study on different species of different age. PMID- 3329651 TI - The role of cytokines in the pathophysiology of T cell mediated skin disease. PMID- 3329650 TI - Malaria presenting as purpura. PMID- 3329652 TI - Immunohistochemical characterization of Spitz's nevus: differentiation from common melanocytic nevus, dysplastic melanocytic nevus and malignant melanoma. PMID- 3329653 TI - Amyloidogenesis in a case of cutaneous amyloidosis: an electron microscopic study using the refixation-reembedding method. PMID- 3329654 TI - Mechanism of blister formation in porphyria cutanea tarda. I. Histopathological observation of blisters in three cases of porphyria cutanea tarda. PMID- 3329656 TI - Mechanisms of reactive oxygen species-induced skin erythema and superoxide dismutase activities in guinea pigs. PMID- 3329655 TI - Cutaneous nerves in patients with diabetic neuropathy--an electron microscopic study. PMID- 3329657 TI - Leukocyte chemotactic activity and circulating immune complexes in psoriasis. PMID- 3329659 TI - Cutaneous changes in trichinellosis seen in Japan. PMID- 3329658 TI - Contemplative immune mechanism of Lucio phenomenon and its global status. PMID- 3329660 TI - Fiberglass dermatitis in Japan--report of four cases. PMID- 3329661 TI - Two unusual cases of deep lymphangioma. PMID- 3329662 TI - Urticarial vasculitis with circulating immune complexes and mixed cryoglobulins: studies on pathogenesis. PMID- 3329663 TI - Multiple necrotizing fasciitis: its etiology and histopathological features. PMID- 3329664 TI - Sebaceous nevus with sweat-gland duct proliferation around the suture material. PMID- 3329666 TI - Evolution in the management of eclampsia. PMID- 3329665 TI - Medical termination of pregnancy and pelvic infections. PMID- 3329667 TI - [Turnover of the fatty acid moiety of complex lipids in blood cell membrane and its physiological significance--activation mechanism of platelet phospholipase A2]. PMID- 3329668 TI - [Regulation of fibroin gene expression and secretion of fibroin in the silk gland]. PMID- 3329669 TI - [Recent development in tetrodotoxin research]. PMID- 3329670 TI - [Bacterial hemoglobin]. PMID- 3329671 TI - [Phospholipase A2 in platelets]. PMID- 3329672 TI - [Protective effect of selenium against heavy metal toxicity and its application in clinical treatments]. PMID- 3329673 TI - Ultrastructural visualization of secretory products by exocytosis in the rat parathyroid gland by using the tannic acid-Ringer incubation method. PMID- 3329674 TI - A multicellular basket for the preparative process in electron microscopy. PMID- 3329675 TI - Identification of the Escherichia coli cysM gene encoding O-acetylserine sulphydrylase B by cloning with mini-Mu-lac containing a plasmid replicon. AB - A region located at around 52' on the Escherichia coli chromosome was cloned by use of mini-Mu-lac containing a plasmid replicon and recloned into pBR322. Enzyme assays on transformants carrying the cloned fragments indicated the presence in the latter of the cysA and cysM genes coding for sulphate permease and O acetylserine sulphydrylase B, respectively. PMID- 3329676 TI - Transformation frequency increases with increase in agitation rate of chemostat cultivated Escherichia coli K12, strain C-600. AB - The transformation frequency of Escherichia coli C-600, continuously cultivated in a chemostat operated at constant dilution rate, increased with increase in agitation rate (impeller speed). Cell counts at each impeller speed remained approximately constant. The phenomenon correlated with changes in mean cell volume associated with the changes in agitation rate. PMID- 3329677 TI - Escherichia coli mutants resistant to uncouplers of oxidative phosphorylation. AB - Two mutant strains of Escherichia coli K 12 Doc-S resistant to the uncoupling agents 4,5,6,7-tetrachloro-2-trifluoromethyl benzimidazole and carbonyl cyanide m chlorophenylhydrazone were isolated. These strains, designated TUV and CUV, were capable of (a) growth, (b) the transport of succinate and L-proline and (c) electron-transport-linked oxidative synthesis of ATP in the presence of titres of uncoupler which inhibited these processes in strain Doc-S. The inhibition of transport of L-proline by a fixed titre of uncoupler was sharply pH dependent in strain Doc-S: uptake was unaffected at pH 7.6 but completely inhibited at pH 5.6. This pH dependence was not shown by the resistant strains. We believe that uncouplers were equally accessible to their site(s) of action in the energy conserving membrane of the sensitive and resistant strains. We conclude that uncoupler resistance in these strains of E. coli has arisen as a consequence of mutations which directly affect a specific site of uncoupler action within the cytoplasmic membrane, rather than as a consequence of a decrease in the permeability of cells to uncoupler. PMID- 3329678 TI - Segregation of proteinase-negative mutants from heterozygous Candida albicans. AB - The extracellular acidic proteinase (EC 3.4.23.6) produced by Candida albicans has been reported to be a virulence factor. In studying the role of this proteinase in human disease, we determined the optimum conditions for stimulating proteinase production in order to isolate proteinase-negative (Prt-) mutants. We found that in liquid medium containing bovine serum albumin (BSA) as the sole nitrogen source, at pH 4 and 27 degrees C, the sensitivity of proteinase detection was considerably greater than when assayed on BSA agar at 37 degrees C. This observation is due, in part, to temperature sensitivity of proteinase induction. Nitrogen starvation did not induce proteinase. Proteinase production on agar was increased by adding 0.01% yeast extract (YE) to BSA medium. Using BSA + YE agar to isolate mutants, it was discovered that C. albicans ATCC 28366 was heterozygous for a Prt- mutation. Spontaneous Prt- mutants occurred at a frequency of 2 x 10(-3). Ultraviolet light increased the mitotic segregation of Prt- cells to a frequency of 1 x 10(-2). The Prt- phenotype showed a large inoculum effect, Prt- segregants reverted with a high frequency, and the revertants were unstable. PMID- 3329679 TI - Cloning and expression in Escherichia coli of an insecticidal crystal protein gene from Bacillus thuringiensis var. aizawai HD-133. AB - Using a gene probe derived from the cloned var. sotto insecticidal crystal protein (ICP) gene, we have cloned a Bacillus thuringiensis var. aizawai HD-133 ICP gene in Escherichia coli. The gene encodes a polypeptide that is toxic to Lepidoptera in vivo and in vitro. The protein is expressed at a level sufficient to produce phase-bright inclusions in recombinant E. coli strains, and these inclusions can be partially purified using discontinuous sucrose density gradients. Immunoblotting shows that the inclusions contain a 135 kDa polypeptide which reacts strongly with antiserum raised against the B. thuringiensis var. kurstaki HD-1 P1 polypeptide. PMID- 3329680 TI - Familial meningiomas. Report of two cases. AB - The Authors report a case of intracranial meningioma in two sisters, with no evidence of neurofibromatosis. A study of the karyotype has been performed; in one patient we have found a pericentric inversion of one chromosome 9. The possible role of the genetical factors in the develop of familial meningiomas is discussed. PMID- 3329681 TI - Pregnancy, epilepsy and pharmacotherapy. PMID- 3329682 TI - Rare poisoning with Cerebra thevetia (a case report). PMID- 3329683 TI - Transient hyperglycemia in neonate (a case report with review of literature). PMID- 3329685 TI - Skeletons give clues to health of fourteenth century London. PMID- 3329684 TI - William Pickles lecture 1987. The professionals. PMID- 3329686 TI - [Sociometric status of children with attention deficit disorder]. PMID- 3329687 TI - [An epidemiological study on renal dysfunction of inhabitants in Cd-exposed areas in the Kakehashi River basin in Ishikawa Prefecture]. PMID- 3329688 TI - Skin vasoconstriction induced by local skin heating. AB - Skin vessels of the human finger and toe can constrict in response to local skin heating. This vascular response is, therefore, not confined only to the skin of animals, such as the sheep's leg, rat's tail, rabbit's ear, and kangaroo's tail. The target of this response appears to be arteriovenous anastomoses of the glabrous side of hand and foot. This "heat-induced" vasoconstriction appears to retard heat input from hot exterior environment. PMID- 3329689 TI - Local effect of vasoactive intestinal polypeptide on human sweat-gland function. AB - Physiological significance of vasoactive intestinal polypeptide (VIP), a putative co-transmitter of the cholinergic neuron innervating sweat glands, was investigated by its local effect on drug-induced sweating. VIP, methacholine chloride (MCH), or VIP plus MCH dissolved in 0.1 ml of 0.9% NaCl solution to a specified concentration was injected intradermally at the center of a forearm test area of 15 cm2 and the sweat rate was recorded continuously by capacitance hygrometry. In a cool environment (Ta, 23 degrees C), VIP failed to cause sweat secretion, but increased the rate of MCH-induced sweating, most markedly at a concentration of 10(-5) g/ml, where the rise in local skin temperature was the greatest. On an area anesthetized by nerve block in a hot environment (Ta, 35 degrees C), the effect was less obvious and less consistent, indicating that the sweat-facilitatory effect of VIP is reduced under the condition of passive cutaneous vasodilation. It may be postulated that VIP plays a role in securing ample oxygen supply to functioning sweat glands, especially with a relatively high cutaneous vasoconstrictor tone. PMID- 3329690 TI - [A clinical study on CEA, TPA, ADA, ferritin, beta 2 microglobulin and sialic acid levels in pleural effusion]. PMID- 3329691 TI - [A case of pulmonary leiomyoma]. PMID- 3329692 TI - An historical survey and prospects of research on EDRF. PMID- 3329693 TI - A medical literature that comments on the theory 'five yun and six qi'. PMID- 3329694 TI - Ventricular fibrillation detection by a regression test on the autocorrelation function. PMID- 3329696 TI - Presence in the 'silent' terminus region of the Escherichia coli K12 chromosome of cryptic gene(s) encoding a new nitrate reductase. AB - A cosmid complementing narG mutants defective in nitrate reductase activity was isolated from a genomic library of Escherichia coli. The restriction map of the insert differed from that of the narGHI operon. The new enzyme, termed NarZ, required molybdenum for activity. The expression of narZ was not affected by the factors controlling narGHI. Insertion mutations indicated that the narZ locus covered about 8 kb of DNA; narZ is located at 32.5 U on the chromosome, in the cotransduction gap near the replication terminus. Southern blot experiments under stringent conditions using narGHI or narZ DNA as probes revealed a large extent of homology, with a small area of very high homology. We propose that narZ and narGHI have descended from a common ancestor by gene duplication. PMID- 3329695 TI - Analysis of the Klebsiella pneumoniae ntrB gene by site-directed in vitro mutagenesis. AB - A number of in-frame insertion and deletion mutations have been constructed in vitro in the Klebsiella pneumoniae ntrB gene and the effects of each mutant NtrB protein on NtrC activity have been assessed after reintroduction of the ntrB mutation into the glnA ntrBC operon. These experiments suggest that the phosphorylation of NtrC catalysed by NtrB not only makes NtrC competent as a transcriptional activator but also improves the DNA-binding properties and hence the negative control functions of NtrC. The variety of NtrB phenotypes obtained suggest a structure/function model for the protein. PMID- 3329697 TI - A gene fusion approach to the study of pullulanase export and secretion in Escherichia coli. AB - A series of fusions between the gene for the Klebsiella pneumoniae secreted lipoprotein pullulanase (pulA) and the genes for cytoplasmic beta-galactosidase (lacZ) or periplasmic alkaline phosphatase (phoA) were created by transposon mutagenesis using mini-MudII1681 or TnphoA, respectively. The hybrid genes were expressed in Escherichia coli K-12 with or without the K. pneumoniae genes that promote pullulanase secretion in E. coli. We characterized seven different pulA lacZ gene fusions encoding hybrid polypeptides containing from 14 to c. 1060 residues of pro-pullulanase. All but the smallest hybrid were fatty acylated and were toxic to producing cells, causing the accumulation of precursors of other exported proteins. Four different pulA-phoA gene fusions encoded hybrids with alkaline phosphatase activity. All four hybrids were fatty acylated, but were not toxic. Although the hybrids were apparently membrane-associated, they were not secreted into the medium either by E. coli carrying pullulanase secretion genes or by K. pneumoniae. Immunofluorescence tests indicated that the pullulanase secretion genes promoted the localization of one of these hybrids to the outer face of the E. coli outer membrane, which may have important implications for the design of live vaccine strains and of immobilized enzymes. PMID- 3329698 TI - [Possible mechanisms of the formation of structures in bacterial populations consisting of motile cells]. AB - The formation of fixed and moving structures was studied in Escherichia coli populations. The moving and fixed structures were shown to be formed only by bacteria with a taxis system. The moving structures caused an uneven distribution of the substrate concentration. Bacterial growth on agar with the unevenly distributed substrate led to the appearance of fixed structures. Mechanisms responsible for the formation of bacterial structures remain obscure. PMID- 3329699 TI - [Fibrinolytic activity of natural variants of Bacillus mesentericus]. AB - The natural variability of the ability to synthesize proteinases by Bacillus mesentericus 64 was studied. The population of this strain was shown to be heterogeneous. Three types of variants (S, M and P) differed in the morphology of their colonies and in the culture characteristics from the typical colonies of the parent strain. The caseinolytic activity of the M variant was three times as high as that of the parent strain, and it also had an elevated fibrinolytic activity and a high rate of blood thrombolysis in experiments in vitro. The rate of proteinase synthesis correlated with the morphological types of sporogenic bacteria. PMID- 3329700 TI - Carcinogenicity and mutagenicity of N-nitroso compounds. AB - The carcinogenic activities in rats and hamsters and the mutagenic activity in Salmonella of a number of N-nitroso compounds belonging to various classes have been compared. While most directly acting N-nitroso compounds and those requiring metabolic activation are mutagenic with appropriate activation and seem to alkylate DNA in vivo, there are exceptions. Some of these are mutagens that are not carcinogenic; others are carcinogens that are nonmutagenic. Even among the mutagenic carcinogens, there is no quantitative relationship between mutagenic and carcinogenic activities. This implies to directly acting compounds and to those requiring metabolic activation. The lack of congruence between the two activities among the nitrosamines is due to the complexity of the metabolic activating processes leading to formation of proximate carcinogens. The deficiencies in the mutagenesis assay appear to arise from a lack of the necessary enzymes in the liver microsomal fractions used for activation. Nitrosamines bearing oxygen on the beta carbon of an alkyl chain are not oxidized by rat microsomal enzymes and hence are not converted to bacterial mutagens by rat liver microsomes. Bacterial mutagenicity is not a guide to carcinogenic activity of N-nitroso compounds or to the mechanisms by which these compounds induce cancer. PMID- 3329701 TI - [Prof. Zofia Majewska (on her 80th birthday)]. PMID- 3329702 TI - [Verbal, visual and aural memory in the early postoperative period in patients treated by thalamotomy]. AB - Verbal memory and learning ability were determined before the operation and immediately 3-4 weeks after stereotactic surgery in 11 patients with extrapyramidal motor disturbances treated by ventrolateral (VL and Vim) thalamotomy. Preoperative examinations demonstrated disturbances of short-term verbal memory with narrowing of its extent and increased susceptibility of the trace to interference. Long-term memory was disturbed also, with presence of difficulties in recall and difficulties in memorization of verbal materials. Directly after the operation, in relation to the preoperative testing, increased disturbances were demonstrated in all stages of verbal memory, after damage to the border area of VL and Vim nuclei in the left as well as in the right thalamus. It was possible to detect some functional differentiation between thalamic lesions, with a tendency for increased disturbances of short-term verbal visual memory after right-sided thalamotomy and verbal auditory memory after left sided thalamotomy. PMID- 3329703 TI - [Update in the therapy of fibrocystic mastopathy]. PMID- 3329704 TI - [Mammography, thermography and ultrasonics in the follow-up of breasts subjected to conservative treatment (quadrantectomy and radiotherapy)]. PMID- 3329706 TI - [Suture material and single layer in cesarean section today]. PMID- 3329705 TI - [Clinical evaluation of desogestrel, the first new-generation progestagen, practil 21, on 13,290 women and 74,967 cycles]. PMID- 3329707 TI - beta-Phenylethylamines and the isoquinoline alkaloids. PMID- 3329709 TI - Comparison of the human and mouse PIM-1 cDNAs: nucleotide sequence and immunological identification of the in vitro synthesized PIM-1 protein. AB - Pim-1 is a putative oncogene which was discovered as a target for transcriptionally activating proviral insertions in T-cell lymphomas in mice. Its genomic and cDNA sequence have been published (Selten et al., 1986, Cell 46, 603 611). We have isolated and sequenced pim-1 cDNA clones from the human leukemia cell line K562 (h-pim-1). Comparison of human and mouse cDNA sequences reveals that both contain: (i) a GC rich leader sequence, (ii) an open reading frame encoding a 313 amino acid protein (94% conserved) showing obvious homology to protein kinases and (iii) a 1.3 kb 3' untranslated region with two polyadenylation signals and five copies of the mRNA destabilizing motif ATTTA. "In vitro" translation experiments show that both mouse and human cDNA derived RNA can translate into a protein of the expected size. Their identity was confirmed by immuno-precipitation with antisera raised against synthetic pim-1 oligopeptides. PMID- 3329708 TI - Measurement of liver haemodynamics. PMID- 3329710 TI - Murine c-myc retroviruses alter the growth requirements of myeloid cell lines. AB - Recombinant retroviruses encoding a murine c-myc gene were utilised to explore the consequences of constitutive c-myc expression for interleukin 3-dependent murine myeloid cell lines. The c-myc virus-infected cells exhibited a diminished requirement for growth factor and serum when grown in soft agar, but no factor independent cells could be isolated and the cells were not tumorigenic. Thus deregulated expression of a c-myc gene at physiological levels apparently renders myeloid cells more responsive to growth factors but cannot abrogate this requirement or render the cells malignant. PMID- 3329711 TI - Characterization of the human PIM-1 gene: a putative proto-oncogene coding for a tissue specific member of the protein kinase family. AB - The mouse PIM-1 gene is involved in the pathogenesis of virally-induced mouse lymphomas. We have cloned and analyzed the human homologue of the mouse PIM-1 gene to investigate its role in human lymphoma and leukemia. Overlapping cDNA clones from a K562 (human erythroleukemia cell line) library were isolated and sequenced. The deduced amino acid sequence showed significant homology to a number of the protein kinases but did not have a transmembrane region. Genomic clones from the 380 cell line (human B cell leukemia) were analyzed. The PIM-1 transcript was found to derive from 5 Kb of genomic DNA. Six exons and five introns were identified. The promoter region has no TATA or CAAT boxes, but did have multiple potential Sp1 binding sites (CCGCCC). Studies of expression of this gene using Northern blots of human cell lines showed it to be transcribed primarily in B lymphoid and myeloid cell lines. The characterization of the human PIM-1 gene will allow the definition of its role in hemopoietic malignancies and in hematolymphoid differentiation. PMID- 3329712 TI - Two adjacent mutations at position 12 activate the K-ras2 oncogene of a human mammary tumor cell line. AB - Among 10 human mammary tumor cell lines analyzed for transforming genes by transfection of NIH 3T3 cells, one carcinoma cell line, H-466B, established from an ascitic effusion of a woman with an adenocarcinoma of the breast was scored as positive. The transforming gene was identified as the K-ras2 oncogene. Nucleotide sequencing of exons 1 and 2 of the activated gene revealed two adjacent G----T transversions at the first and second position in codon 12 leading to the replacement of the normally encoded glycine by a phenylalanine. Since the phenylalanine substitution had never been observed in any type of tumor, this raises the question about the frequency as well as the cell type specificity of this K-ras2 activation in mammary tumors. PMID- 3329713 TI - Human ros1 and mas1 oncogenes located in regions of chromosome 6 associated with tumor-specific rearrangements. AB - Oncogenes have been implicated in tumorigenesis based on their localization to chromosomal sites associated with tumor-specific structural rearrangements. We have mapped the human ros1 (formerly mcf3) and mas1 oncogenes to the distal half of chromosome 6q, within a region frequently rearranged in malignant cells. Chromosomal mapping of these two new human transforming genes may help elucidate the involvement of the long arm of chromosome 6 in diverse tumor types. PMID- 3329714 TI - Expression of c-myc is under dietary control in rat liver. AB - Expression of c-myc has often been related to the control of growth and differentiation of a variety of cell types. However, in some cases, such a relation has not been found. The rate of cell division is very low in liver, but c-myc expression is yet easily detected. We show here that a short-time physiological fasting results in a dramatic decrease of c-myc expression in rat liver. This effect does not seem to be dependent on glucagon, since administration of glucagon leads to an increase in c-myc mRNA. This is to our knowledge, the first evidence of a physiological variation of proto-oncogene expression linked to food intake, and we suggest that this variation could play a role in liver cell growth control. PMID- 3329715 TI - Multiple activated oncogenes in human tumors. PMID- 3329717 TI - The human int-1 gene is located at chromosome region 12q12-12q13 and is not rearranged in myxoid liposarcoma with t(12;16) (q13;p11). AB - The mouse cellular oncogene int-1 is often transcriptionally activated as a consequence of nearby proviral insertions in mouse mammary tumors. A highly conserved sequence has been found in the human genome, called int-1 gene, the role of which in human tumors is not known. By somatic hybrids, the human int-1 gene has been assigned to the segment 12q14-12pter. Using a genomic DNA clone containing the fourth exon of the human int-1 gene we have mapped the human int-1 gene to 12q12-12q13. To determine whether this gene, which is located close to the 12q13 breakpoint associated with myxoid liposarcoma, is rearranged in these tumors, we have performed Southern blot analysis of DNA from myxoid liposarcomas carrying the translocation t(12;16) (q13;p11). In the two tumors investigated, the translocation does not disrupt the int-1 gene. PMID- 3329716 TI - The human EGF receptor gene: structure of the 110 kb locus and identification of sequences regulating its transcription. AB - The human epidermal growth factor receptor (EGFR) proto-oncogene is shown to span 110 kb of DNA divided into 26 exons. Analysis of sequences surrounding exon 1 reveals a highly CG rich region which promotes transcription. The activity of the EGF receptor promoter can be modulated by E1A protein and receptor RNA levels increased by stimulation with phorbol ester or fetal calf serum. Promoter activity is assayed by linkage to the chloramphenicol acetyl transferase gene and transfection in three cell lines, with quantitation of plasmid DNA uptake by isolation of a Hirt supernatent from each transfection. Deletion analysis of the CG rich promoter region of the gene and construction of chimeric EGFR/SV40 promoters are used to demonstrate positive transcription elements located both within exon 1 and 5' to the start of transcription. Negative regulation of transcription by sequences within a -140 to +80 region is suggested. Cotransfection experiments suggest a requirement for the interaction of DNA binding protein Sp1 for maximal activity. Finally, derepression of a positive regulatory sequence located in exon 1 during cotransfection experiments is shown. Results are discussed in reference to the multilevel regulation of EGF receptor expression. PMID- 3329718 TI - Human cellular fps/fes cDNA rescued via retroviral shuttle vector encodes myeloid cell NCP92 and has transforming potential. AB - We have generated a cDNA copy of human c-fps/fes from a 13 kb genomic DNA by means of a retroviral shuttle vector, and have begun characterization of its biological and biochemical properties. The cDNA was able to direct the in vitro synthesis of a protein that was indistinguishable from myeloid cell c-fps/fes NCP92 by immunoprecipitation with specific antisera, electrophoretic mobility, tryptic fingerprint analysis, and its associated protein kinase activity. When the coding sequence of the gag-v-fps/fes P108 fusion protein in Gardner Arnstein Feline sarcoma virus was substituted with the recovered cDNA, the recombinant plasmid directed the expression of NCP92 in NIH 3T3 cells but no morphological transformation was observed. By contrast, when viral gag sequences were linked to the N-terminus of NCP92, the chimeric gene induced foci of transformed cells. These transformants were capable of anchorage independent growth, were tumorigenic in nude mice, and expressed a gag fusion protein kinase of high specific activity. The biological properties of this recombinant are discussed. We conclude that normal human c-fps/fes can be activated by N-terminal linkage to gag. PMID- 3329719 TI - Forskolin and a tumor promoter are able to induce c-fos and c-myc expression in normal, but not in a v-ras-transformed rat thyroid cell line. AB - The rat thyroid cell line (FRTL5) is dependent on thyrotropic hormone (TSH) for its growth. c-fos and c-myc oncogenes expression was measured in these cells after addition of their specific growth factor TSH and after treatment with either forskolin, an activator of adenylate cyclase or with a tumor promoter, TPA. Transient expression of oncogenes coding for nuclear products and a slight increase in ras-h oncogene expression were observed in normal rat thyroid cells after all treatments. In contrast, in v-ras-transformed rat thyroid cells, which express very high levels of p21, treatment with either TSH, forskolin or TPA does not induce c-fos gene expression, while c-myc expression was constitutive. Normal unstimulated cells show no c-myc expression. PMID- 3329720 TI - S. Burt Wolbach, MD: 1880-1954. PMID- 3329722 TI - An immunohistochemical study of islet cells with macronuclei in infancy. AB - The presence of hypertrophic islet cells in infancy as evidenced by nuclear enlargement (2 to 6 times normal size) has been mentioned as a morphological accompaniment of hyperinsulinemic hypoglycemia of infancy. We report an immunohistochemical and semiquantitative study of hypertrophic islet cells in 14 infants with neonatal hypoglycemia (10 with documented persistent neonatal hypoglycemia and 4 with probable persistent neonatal hypoglycemia) and 6 infants born to diabetic mothers (IDM), using an indirect immunoperoxidase methods for the demonstration of insulin, somatostatin, and glucagon. Quantitation of immunoreactivity was performed in each case on 20 hypertrophic cells. Polyploid cells were positive for insulin and somatostatin but negative for glucagon; insulin-positive cells outnumbered somatostatin-positive cells in both groups. As nuclear hypertrophy is considered to be a sign of hyperfunction, our findings are in accordance with the concept that IDM involves reactive beta-cell hypertrophy and similar findings in the pancreases of infants with persistent neonatal hypoglycemia (PNH) suggest a primary dysfunction of their beta cells, too. PMID- 3329721 TI - Renal histopathology in Alagille's syndrome. AB - Various renal abnormalities have been reported in Alagille's syndrome (arteriohepatic dysplasia), usually as single case reports. The renal findings at autopsy of four patients with Alagille's syndrome, ranging in age from 4 1/2 months to 7 years, 2 of whom had evidence of renal dysfunction, are described and are compared with kidneys from patients with other cholestatic liver diseases of childhood. Two of the Alagille's patients had histologic findings suggestive of membranous nephropathy and special stains revealed accumulation of lipid in the glomerular and tubular basement membranes. Immunofluorescence of 1 revealed extensive accumulation of IgG and IgM. One patient had medullary cysts and mild interstitial fibrosis, and the fourth had a large subcapsular cyst and mild tubulointerstitial nephritis. All 4 cases, when examined with the electron microscope, revealed varying degrees of basement membrane thickening, splitting, and vacuolation with dense osmiophilic particles, most prominent in the patients with membranous nephropathy. These ultrastructural findings did not correlate with the degree of hyperlipidemia, but rather with the patient's age, and were also observed in other cholestatic diseases. The findings suggest that Alagille's syndrome is frequently associated with renal abnormalities, including lipid deposition, which may in some instances, lead to clinically significant renal impairment. PMID- 3329723 TI - Tinnitus. PMID- 3329724 TI - Radiological investigations of the urinary tract. PMID- 3329725 TI - A domain of the Klenow fragment of Escherichia coli DNA polymerase I has polymerase but no exonuclease activity. AB - The Klenow fragment of DNA polymerase I from Escherichia coli has two enzymatic activities: DNA polymerase and 3'-5' exonuclease. The crystal structure showed that the fragment is folded into two distinct domains. The smaller domain has a binding site for deoxynucleoside monophosphate and a divalent metal ion that is thought to identify the 3'-5' exonuclease active site. The larger C-terminal domain contains a deep cleft that is believed to bind duplex DNA. Several lines of evidence suggested that the large domain also contains the polymerase active site. To test this hypothesis, we have cloned the DNA coding for the large domain into an expression system and purified the protein product. We find that the C terminal domain has polymerase activity (albeit at a lower specific activity than the native Klenow fragment) but no measurable 3'-5' exonuclease activity. These data are consistent with the hypothesis that each of the three enzymatic activities of DNA polymerase I from E. coli resides on a separate protein structural domain. PMID- 3329726 TI - Cloning, expression, and nucleotide sequence of livR, the repressor for high affinity branched-chain amino acid transport in Escherichia coli. AB - The livR gene encoding the repressor for high-affinity branched-chain amino acid transport in Escherichia coli has been cloned from a library prepared from the episome F106. The inserted DNA fragment from the initial cloned plasmid, pANT1, complemented two independent, spontaneously derived, regulatory mutations. Subcloning as well as the creation of deletions with Bal31 exonuclease revealed that the entire regulatory region is contained within a 1.1-kb RsaI-SalI fragment. Expression of the pANT plasmids in E. coli minicells showed that the regulatory region encodes one detectable protein with an apparent molecular weight of 21,000. DNA sequencing revealed one open reading frame of 501 bp encoding a protein with a calculated MW of 19,155. The potential secondary structure of the regulatory protein has been predicted and it suggests that the carboxy terminus may fold into three consecutive alpha helices. These results suggest that the livR gene encodes a repressor which plays a role in the regulation of expression of the livJ and the livK transport genes. PMID- 3329727 TI - Isolation and characterization of native human renin derived from Chinese hamster ovary cells. AB - Transfection of Chinese hamster ovary (CHO) cells with a plasmid containing the cDNA for human preprorenin has provided cell lines that secrete 15 mg of native prorenin per liter of culture medium. Tryptic activation of the prorenin occurs by selective cleavage of the Arg66-Leu67 bond (numbering as in preprorenin). The renin product, purified in a single step and in high yield by affinity chromatography, is fully stable for as long as 8 months when stored in solution at 4 degrees C and pH 6.5. Purity of the renin was judged to be greater than 95% by gel electrophoresis, compositional and N-terminal sequence analyses, and specific enzyme activity. An important aspect of the present work is the development of a direct assay for renin which permits accurate and reproducible evaluation of enzyme units and kinetic parameters. Application of methods described herein, combined with appropriate scale-up fermentation capabilities, provides the means for generating gram quantities of human renin and its zymogen. PMID- 3329728 TI - Set of novel, conserved proteins fold pre-messenger RNA into ribonucleosomes. PMID- 3329730 TI - Kinetic characterization of early intermediates in the folding of E. coli tryptophan-synthase beta 2 subunit. AB - This report describes the use of fluorescence energy transfer between an intrinsic energy donor (tryptophan 177) and two chemically added acceptors to study intermediates in the folding of the beta 2 subunit of E. coli tryptophan synthase. Two early folding steps are thus identified and characterized. One is very rapid (its rate constant at 12 degrees C is 0.02 sec-1) and corresponds to the folding of the N-terminal domain into a structure whose overall features approximate well those of the native domain. The second step is somewhat slower (its rate constant at 12 degrees C is 0.008 sec-1) and involves a conformational rearrangement of the N-terminal domain brought about by the interactions between the N- and C-terminal domains within a monomeric beta chain. This brings to five the number of intermediates which have been identified and ordered on the folding pathway of the dimeric beta 2 subunit. PMID- 3329729 TI - The DNA replication inhibitor microcin B17 is a forty-three-amino-acid protein containing sixty percent glycine. AB - Microcin B17 is a low-molecular-weight protein that inhibits DNA replication in a number of enteric bacteria. It is produced by bacterial strains which harbor a 70 kilobase plasmid called pMccB17. Four plasmid genes (named mcbABCD) are required for its production. The product of the mcbA gene was identified by labelling minicells. The mcbA gene product was slightly larger when a mutation in any of the other three production genes was present. This indicates that these genes are involved in processing the primary mcbA product to yield the active molecule. The mcbA gene product predicted from the nucleotide sequence has 69 amino acids including 28 glycine residues. Microcin B17 was extracted from the cells by boiling in 100 mM acetic acid, 1 mM EDTA, and purified to homogeneity in a single step by high-performance liquid chromatography through a C18 column. The N terminal amino acid sequence and amino acid composition demonstrated that mcbA is the structural gene for microcin B17. The active molecule is a processed product lacking the first 26 N-terminal residues. The 43 remaining residues include 26 glycines. While microcin B17 is an exported protein, the cleaved N-terminal peptide does not have the characteristic properties of a "signal sequence", which suggests that it is secreted by a mechanism different from that used by most secreted proteins of E. coli. PMID- 3329731 TI - Molecular structure and evolution of adrenergic and cholinergic receptors. PMID- 3329732 TI - Primary structure of the reaction center from Rhodopseudomonas sphaeroides. AB - The reaction center is a pigment-protein complex that mediates the initial photochemical steps of photosynthesis. The amino-terminal sequences of the L, M, and H subunits and the nucleotide and derived amino acid sequences of the L and M structural genes from Rhodopseudomonas sphaeroides have previously been determined. We report here the sequence of the H subunit, completing the primary structure determination of the reaction center from R. sphaeroides. The nucleotide sequence of the gene encoding the H subunit was determined by the dideoxy method after subcloning fragments into single-stranded M13 phage vectors. This information was used to derive the amino acid sequence of the corresponding polypeptide. The termini of the primary structure of the H subunit were established by means of the amino and carboxy terminal sequences of the polypeptide. The data showed that the H subunit is composed of 260 residues, corresponding to a molecular weight of 28,003. A molecular weight of 100,858 for the reaction center was calculated from the primary structures of the subunits and the cofactors. Examination of the genes encoding the reaction center shows that the codon usage is strongly biased towards codons ending in G and C. Hydropathy analysis of the H subunit sequence reveals one stretch of hydrophobic residues near the amino terminus; the L and M subunits contain five such stretches. From a comparison of the sequences of homologous proteins found in bacterial reaction centers and photosystem II of plants, an evolutionary tree was constructed. The analysis of evolutionary relationships showed that the L and M subunits of reaction centers and the D1 and D2 proteins of photosystem II are descended from a common ancestor, and that the rate of change in these proteins was much higher in the first billion years after the divergence of the reaction center and photosystem II than in the subsequent billion years represented by the divergence of the species containing these proteins. PMID- 3329733 TI - Proteases of enhanced stability: characterization of a thermostable variant of subtilisin. AB - A procedure has been developed for the isolation and identification of mutants in the bacterial serine protease subtilisin that exhibit enhanced thermal stability. The cloned subtilisin BPN' gene from Bacillus amyloliquefaciens was treated with bisulfite, a chemical mutagen that deaminates cytosine to uracil in single stranded DNA. Strains containing the cloned, mutagenized subtilisin gene which produced subtilisin with enhanced thermal stability were selected by a simple plate assay procedure which screens for esterase activity on nitrocellulose filters after preincubation at elevated temperatures. One thermostable subtilisin variant, designated 7150, has been fully characterized and found to differ from wild-type subtilisin by a single substitution of Ser for Asn at position 218. The 7150 enzyme was found to undergo thermal inactivation at one-fourth the rate of the wild-type enzyme when incubated at elevated temperatures. Moreover, the mid point in the thermally induced transition from the folded to unfolded state was found to be 2.4-3.9 degrees C higher for 7150 as determined by differential scanning calorimetry under a variety of conditions. The refined, 1.8-A crystal structures of the wild-type and 7150 subtilisin have been compared in detail, leading to the conclusion that slight improvements in hydrogen bond parameters in the vicinity of position 218 result in the enhanced thermal stability of 7150. PMID- 3329734 TI - Primary structure of a precursor to the aspartic proteinase from Rhizomucor miehei shows that the enzyme is synthesized as a zymogen. AB - In order to characterize the zymogen of the milk-clotting enzyme from Rhizomucor miehei, we constructed a cDNA library on pBR327 in Escherichia coli. Aspartic proteinase-specific recombinants were isolated by colony hybridization to a specific oligonucleotide mixture, and the cDNA sequence corresponding to a precursor form of the enzyme was determined. The deduced amino acid sequence shows that this secreted fungal proteinase is synthesized as a precursor. The first 22 amino acid residues in this precursor constitute a typical signal peptide. The amino acid sequence of the following 47-amino-acid-long prosegment shows homology to the prosegments from both the extracellular and intracellular vertebrate aspartic proteinases, and to the prosegments from the yeast and Mucor pusillus aspartic proteinases as well. These observations suggest that all aspartic proteinases are synthesized with a prosegment and that this prosegment is essential for the correct folding of all the mature enzymes. The active Rhizomucor miehei enzyme consists of 361 amino acid residues with a total molecular weight of 38,701. Clusters of identities around the active site cleft support the assumption that these proteinases have a common folding of their peptide chains. The disulphide bridges were localized in the fungal enzyme, and 2 N-glycosylation sites were identified. PMID- 3329735 TI - Quality of life in psychosomatic research. A psychometric model. AB - The concept of 'quality of life' has had a paradigmatic effect in psychosomatic medicine by focussing on the measurements of psychological distress. This concept has been phenomenologically described under such names as discomfort and psychological boredom. Elements of fatigue, anxiety and depression seem to be core symptoms of dysfunctions in quality of life. An objective and nomothetic approach to quality of life has been demonstrated in this review when referring to the instrumental use of rating scales, e.g. the General Health Questionnaire. Furthermore, it has been recommended to follow the multiaxial approach of DSM-III including dimensions of personality, psychosocial stressors and social functioning. PMID- 3329736 TI - The commonest glomerulonephritis in the world: IgA nephropathy. PMID- 3329737 TI - Small intestinal motor activity--its role in gut homeostasis and disease. AB - The study of small intestinal motor activity has certainly emerged from relative obscurity to a position where it may indeed become an important clinical tool. Modern technology has led to a considerable increase in our understanding of the physiology of motor function and has brought us to a stage where small intestinal motility is amenable to study in man. It is clear that coordinated motor function of the small intestine is central to integrated digestive function. Normal patterns, and in particular normal variants, are still being defined, and both the investigator and the clinician need to be particularly aware of interspecies, intersubject and interregional variations. While in some instances, abnormal motility is clearly related to an underlying disorder of intestinal neuromuscular function, in others, and in particular in functional gastrointestinal disorders, the overall experience of intestinal motility recordings in man is still too limited to allow us to declare with confidence whether reported abnormalities are, indeed, truly aberrant patterns or whether they are causally related to a given patient's symptoms. PMID- 3329738 TI - Propranolol in chronic liver disease: a controlled trial of its effect and safety over twelve months. AB - The effect and safety of propranolol (Inderal-LA) in 95 patients with mild to moderate chronic liver disease was studied in a double-blind placebo controlled trial. Over a 12-month period, three patients in the propranolol group died compared with eight in the control population. Upper gastrointestinal bleeding occurred in the placebo group only. Twenty-five patients were withdrawn, 12 in the propranolol and 13 in the placebo group. No deterioration in clinical condition or liver function tests was observed in the propranolol-treated patients, although serum testosterone levels fell significantly compared with the control patients. This study shows that long-term treatment with propranolol is safe in patients with chronic liver disease but further studies are required to define whether or not patients will benefit. Our observations on the response to placebo suggest that a significant proportion of patients are not likely to tolerate drug treatment for portal hypertension well. PMID- 3329740 TI - A potpourri of historical memorabilia. The opening address of the Conference in Scarborough, July 1987. PMID- 3329739 TI - Hydralazine sensitivity: clinical features, autoantibody changes and HLA-DR phenotype. AB - The clinical features, autoantibody changes, acetylator and HLA-DR phenotype of 20 patients with hydralazine-induced systemic lupus erythematosus are described. Four cases of particular interest are discussed in greater detail. Hydralazine sensitivity is more common in women, slow acetylators and the HLA-DR4 phenotype. Symptoms can occur even after many years of treatment and clinical awareness must be maintained for all patients to detect sensitivity at an early stage; there is no timely safe dose even in rapid acetylators. Joint symptoms predominate and full resolution is usual on discontinuing hydralazine. Failure of resolution should raise the suspicion of an underlying cause for the arthritis. PMID- 3329741 TI - Protection today and tomorrow--the Euratom Directive. PMID- 3329742 TI - The use of a proforma in obstetric ultrasound. PMID- 3329744 TI - Electroconformational coupling and membrane protein function. PMID- 3329743 TI - Thanatophoric dwarfism--a case study. PMID- 3329745 TI - Characterization of metal centres in biological systems by X-ray absorption spectroscopy. PMID- 3329746 TI - Predominance of locally-produced prostaglandin E2 over prostacyclin in skin incisions in man. AB - Blood was collected from skin incisions made by the 'Simplate' technique in 8 healthy men. Prostaglandin (PG) E2, but not 6-oxo-PGF1 alpha, the stable hydrolysis product of prostacyclin (PGI2), was tentatively identified using capillary column gas chromatography/electron capture mass spectrometry. It was not possible to quantify PGE2 because of the small volumes of blood generated by this method. Larger blood samples were then collected from 22 skin incisions in 13 patients undergoing cardiothoracic surgery. Concentrations of PGE2 were substantially greater than 6-oxo-PGF1 alpha in every sample. 13,14-Dihydro-15-oxo PGF2 alpha, a pulmonary metabolite of PGE2, was not elevated, indicating that the PGE2 was synthesised locally at the site of incision. In 6 further patients undergoing cardiac surgery, blood sampled from an antecubital vein before and during operation contained little or no PGE2. We conclude that a substantial proportion of the PGE2 in blood emerging from skin incisions may be formed locally by the traumatised microvessels, consistent with the hypothesis that PGE2 is the principle prostaglandin synthesised by human cutaneous microvessels in vivo. PMID- 3329747 TI - [Trial use of embryonal and early-fetal thymus extracts in the treatment of non healing skin defects. II. Crural ulcers in humans]. PMID- 3329748 TI - [Usefulness of immunomorphological studies in the differential diagnosis of various forms of eczema and atopic dermatitis]. PMID- 3329749 TI - [Results of Tigason treatment of children with severe forms of psoriasis and ichthyosis]. PMID- 3329750 TI - [Benzoyl superoxide in the treatment of crural ulcers]. PMID- 3329751 TI - [Ashy dermatosis: review of literature and case report]. PMID- 3329752 TI - [Natural cytotoxic cells (NK cells): biological and pathological aspects]. PMID- 3329753 TI - [Psychiatric nursing as a degree discipline in nursing in Brazil: a vision of the whole]. PMID- 3329754 TI - [Prostaglandins in primary dysmenorrhea. Effect of ketoprofen]. PMID- 3329755 TI - [Dr. Theodore Durrigl's 60 years of life and 30 years of work in rheumatology]. PMID- 3329757 TI - [Enteropathogenic agents isolated from intestinal juice in children with acute and protracted diarrhea]. PMID- 3329756 TI - [Double-blind study of the effects of piroxicam (Erazon) cream in degenerative and extra-articular rheumatism]. PMID- 3329758 TI - [Comparative study of diazepam and lorazepam by oral route, associated with meperidine in preanesthetic medication]. PMID- 3329759 TI - [Traumatic duodenal hematoma: report of a case clinically treated]. PMID- 3329760 TI - [Beta 2 microglobulin in lymphoproliferative status]. PMID- 3329761 TI - Seroepidemiology of hepatitis A and B in two urban communities of Rio de Janeiro, Brazil. PMID- 3329762 TI - [Infection by Listeria monocytogenes after a renal transplant. Report of 6 cases]. PMID- 3329763 TI - The effect of low CO concentrations on the organism. PMID- 3329765 TI - [Arsenic. Elements in the aquatic environment II. Biotic and abiotic systems]. PMID- 3329764 TI - A comparison of direct and indirect measurements of oxygen delivery and consumption: the effects of prostacyclin in two human volunteers. AB - To examine the relation of oxygen delivery to uptake in normals, we have measured cardiac index, oxygen delivery and oxygen consumption directly and indirectly in two human volunteers before and during a prostacyclin (PGI2) infusion (5 ng/kg/min). We have also investigated the relation of direct and indirect measurements of delivery to consumption in two critically ill patients over a more prolonged study period of 24 hours. Overall, there were close correlations between both cardiac index measured by thermodilution with that calculated from the Fick equation (r = 0.97 p less than 0.001) and oxygen consumption measured directly by analysis of inspired gases (V O2) with that calculated by the reverse Fick method (OUI) (r = 0.95 p less than 0.001). Nevertheless, the limits of agreement between the two methods were wide (1.6 L/min.m2 for the cardiac index and 70.5 ml 02/min.m2 for oxygen consumption, 95% confidence limits). In the two human volunteers, PGI2 produced substantial increases in oxygen delivery but there was no change in oxygen consumption measured directly or indirectly; V O2 and OUI were unrelated and independent of oxygen delivery. However, in the two patients studied over 24 hours, there were close correlations between delivery and both V O2 (r = 0.93 p less than 0.001) and OUI (r = 0.94 p less than 0.001). These results suggest that the derivation of oxygen consumption by the reverse Fick method (OUI) is a reasonable substitute for direct measurements of V O2 but occasionally the absolute values so obtained may be somewhat different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3329766 TI - Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies. AB - We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications. PMID- 3329767 TI - A flexible loading dose schedule for warfarin therapy. AB - A flexible loading dose schedule for inducing anticoagulation with warfarin was assessed in 31 consecutive patients. 55% reached the therapeutic range (prothrombin ratio between 2 and 4:1) by Day 2 (40 hours after the first dose) and this figure rose to 77% on Day 3 and to 87% on Day 4. All patients had a PTR between 1.7 and 4.2 on Day 5. Patients with evidence of cardiac failure and abnormal liver function, and those taking medications known to interact with warfarin required lower doses and ran a higher PTR when compared with the total group of patients. This schedule offers a useful means of safely and rapidly inducing warfarin therapy in all patients. PMID- 3329768 TI - Digital subtraction angiography. AB - Digital Subtraction is a computerised radiological technique to demonstrate the vascular tree by removing unwanted background information and enhancing dilute contrast medium within the blood vessels. Contrast may be introduced intravenously or intra-arterially. The relative merits of these two methods, together with the advantages and limitations of the technique are discussed. PMID- 3329769 TI - Bone marrow necrosis in acute lymphoblastic leukaemia. AB - Bone marrow necrosis, an uncommon finding in acute lymphoblastic leukaemia, has previously been regarded as a poor prognostic feature. It has been associated with difficulty in establishing the diagnosis, a low rate of remission as well as short remission duration. We report a case of bone marrow necrosis in a girl with acute lymphoblastic leukaemia and good prognostic features who attained complete remission uneventfully and will discuss previous reports of this association in the literature. PMID- 3329770 TI - Bicentenary of Sir John Forbes (1787-1861). AB - This year is the bicentenary of the birth of the distinguished Scottish physician, Sir John Forbes, famous for his translation of the great French medical classic, De L'Auscultation Mediate by R.T.H. Laennec, the inventor of the stethoscope. PMID- 3329771 TI - [Milan Vasic's monograph on chorea]. PMID- 3329773 TI - On the centennary of Gyorgy Hevesy's birth. PMID- 3329772 TI - Hungarian-Polish medical relations in the past decades. PMID- 3329774 TI - Characteristics of bone marrow fibroblasts and their significance in hematopoiesis. AB - Effective hematopoiesis is thought to be maintained by interplaying between the hematopoietic stem cells (HSC) and their supporting stroma which supply an appropriate environment for HSC lodgement, proliferation and differentiation in the bone marrow. Many experiments have made it apparent that the bone marrow microenvironment is essential for normal hematopoiesis. Several recent reports have shown that most human bone marrow adherent cells under long-term liquid cultures are fibroblasts. In this article, the characteristics of the stromal fibroblasts and their role for HSC maintenance and differentiation are described. PMID- 3329775 TI - Study of renovascular hypertension in rats. IV. Renal arterial blood velocity in one-clip, two-kidney hypertensive rats. AB - In one-clip, two-kidney hypertensive models of rats, the renal arterial blood velocity was recorded using the bidirectional Doppler velocimeter before and at various times after clipping of the renal arteries. In all the rats, immediately after placement of a clip, the blood velocity of the stenosed artery was lowered significantly. Although the blood velocity remained low 2 weeks after clipping, it recovered to the pre-clip level at 6 and at 11 to 13 weeks after clipping. The plasma renin activity tended to decrease following the acute, high-renin stage of hypertension. If it can be assumed that the blood velocity is one of the indexes representing blood flow, its return to the pre-clip normal level in the chronic stage of renovascular hypertension may signify recovery of blood flow to the clipped kidney leading to a reduction in renal renin synthesis and consequently a decrease in plasma renin activity. PMID- 3329776 TI - Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea. AB - Ovalocytosis, an hereditary condition in which most erythrocytes are oval in shape, is a polymorphism that occurs in up to 20% or more of the population in Papua New Guinea and Malaysia. Due to the geographical correlation of the trait with endemic malaria, the possibility of a selective advantage in resistance to malaria has been raised. In a study of 202 individuals with greater than or equal to 50% oval red cells matched by age, sex and village of residence with controls having less than or equal to 30% oval cells, ovalocytic subjects had blood films negative for Plasmodium vivax (P = 0.009), for P. falciparum (P = 0.044), and for all species of malaria parasites (P = 0.013), more often than controls. Among individuals parasitaemic at any time there were no clear differences in density of parasitaemia. However, in children 2 to 4 years old, parasite densities of both species were lower in ovalocytic subjects than in controls (0.01 less than P less than 0.025). The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present. PMID- 3329777 TI - Biological advantage of Plasmodium falciparum isolates resistant to quinine. PMID- 3329778 TI - The antimalarial action on Plasmodium falciparum of qinghaosu and artesunate in combination with agents which modulate oxidant stress. AB - The antimalarial activity of qinghaosu (artemisinine) against Plasmodium falciparum in culture was enhanced by increased oxygen tension. Artesunate, a qinghaosu derivative, showed synergistic effects with miconazole, and with doxorubicin, both of which have been suggested to exert their chemotherapeutic effect through increasing the oxidant stress. In contrast, catalase, dithiothreitol and alpha-tocopherol reduced the effectiveness of qinghaosu in vitro. These results suggest that the action of qinghaosu and artesunate might involve increase in oxidant stress on the infected red cells. PMID- 3329779 TI - Synergistic antimalarial activity of dapsone/dihydrofolate reductase inhibitors and the interaction of antifol, antipyrimidine and antipurine combinations against Plasmodium falciparum in vitro. AB - Using low folate, low p-aminobenzoic acid medium, 2 isolates of Plasmodium falciparum were tested in vitro against a wide range of antimetabolite compounds with known or potential antimalarial activity. ID50 values (the concentration of compound causing 50% inhibition of [3H]hypoxanthine incorporation) were determined for each compound against both isolates. The compounds tested may affect folate, pyrimidine or purine metabolism in malaria parasites and various combinations of compounds were examined for further synergistic antimalarial effects. The combination of any of the dihydrofolate reductase inhibitors cycloguanil, pyrimethamine or WR 99210 with the sulphone drug dapsone demonstrated strongly synergistic antimalarial activity. Combinations of dihydrofolate reductase inhibitors with the antipyrimidine compounds pyrazofurin or menoctone, or with the antipurine compounds tubercidin, bredinin or hadacidin, or with primaquine, failed to demonstrate synergistic activity. Most combinations of an antipurine with an antipyrimidine compound also failed to show any synergistic effect. However, weak synergism was consistently seen in the tubercidin/pyrazofurin and tubercidin/menoctone combinations. Over the 48 h intraerythrocytic cycle using tightly synchronized parasites, tubercidin demonstrated both a cytotoxic and a cytostatic effect. PMID- 3329780 TI - Comparative efficacy of alternative primary therapies for Plasmodium falciparum infections in Malawi. AB - In Malawi, where high levels of chloroquine resistance were shown using a modified 7-day in vivo test, amodiaquine and pyrimethamine-sulfadoxine were evaluated as alternative initial therapies for Plasmodium falciparum infections in children under 5 years old. Therapy success rates, judged by parasite clearance by day 7 after initiation of therapy, were significantly greater among 39 children treated with amodiaquine at 10 mg/kg (90%), 37 receiving amodiaquine at 25 mg/kg (97%), and 34 receiving pyrimethamine-sulfadoxine (100%) at a dose of 25 mg sulfadoxine/kg, than among those treated with chloroquine at a dose of 25 mg/kg (59%) (P = 0.01). Extension of the follow-up period of those receiving amodiaquine (25 mg/kg) and pyrimethamine-sulfadoxine to 21 d revealed a progressively increasing rate of parasite recrudescence in the amodiaquine group (34%), but no recrudescence in the pyrimethamine-sulfadoxine group. These results suggest that, in Malawi, amodiaquine and pyrimethamine-sulfadoxine are superior to chloroquine in producing prompt clearance of P. falciparum parasites among young children, and that pyrimethamine-sulfadoxine alone is superior to the 4 aminoquinolines in sustaining P. falciparum clearance. PMID- 3329782 TI - The haematocrit centrifuge smear technique for the detection of mammalian Plasmodium. PMID- 3329781 TI - Plasmodium falciparum in vitro schizont maturation tests in Mozambique are not improved by removing immune parasite carriers' plasma. AB - To study the effect of immune parasite carriers' plasma on Plasmodium falciparum schizont maturation, peripheral blood stages were incubated for 24-40 h in RPMI medium with either 5% carrier's plasma + 5% non-immune AB serum or 10% non-immune serum. The number of schizonts per 200 asexual P. falciparum was lower in non immune serum than in the presence of carrier's plasma in 19 of 26 cases, due to increased frequency of schizont rupture when carrier's plasma was absent. It is concluded that, under these test conditions, the replacement of immune plasma by non-immune serum makes schizont maturation tests, which are based on the proportion of schizonts among asexual P. falciparum as a measure of growth, more difficult to interpret. PMID- 3329783 TI - Is chloroquine-resistant Plasmodium falciparum malaria emerging in Senegal or The Gambia? PMID- 3329784 TI - The dependence of cell-mediated immune activation in malaria on age and endemicity. AB - In vitro, neopterin, a pyrazino-[2, 3-d]-pyrimidine compound, is produced by human monocytes-macrophages following induction by either supernatants from activated T lymphocytes or by recombinant gamma interferon. In vivo, its determination in urine or serum provides a sensitive and specific test for the activation grade of cell-mediated immune reactions. Urinary neopterin levels were measured in 128 Tanzanian individuals (age 6 months to 54 years) with parasitologically proven malaria. Levels in a subgroup of 117 previously untreated patients were compared with those previously reported from 19 untreated malarial patients from Bangkok, Thailand (age 7 to 62 years). The influence of concomitant variables such as age, fever, parasitaemia, duration of symptoms and local endemicity of malaria upon neopterin excretion levels was analysed. In the Thai patients, levels were considerably higher than in Tanzanian subjects of similar age. Among the Tanzanian patients, an overwhelming influence of age was detected, children showing extremely high neopterin excretion levels. The other variables did not influence neopterin levels significantly. Our findings are in accord with recent data on the prevalence and mean titres of antibodies to the circumsporozoite protein of Plasmodium falciparum, which indicate that in endemic areas acquired humoral immunity develops slowly with increasing age, while prevalence and severity of disease decline. PMID- 3329785 TI - Trypanosoma cruzi strain-specific monoclonal antibodies: identification of Colombian strain flagellates in the insect vector. AB - Spleen cells from mice immunized with insect-derived Trypanosoma cruzi metacyclic trypomastigotes were used to obtain Colombian strain-specific monoclonal antibodies. At least 4 different strain-specific antigens were recognized by the monoclonal antibodies on epimastigotes or metacyclic trypomastigotes. There was no reactivity with other stages of Colombian strain T. cruzi, nor with any stage of 15 other T. cruzi strains or isolates, nor with 22 other Trypanosomatidae. One of the monoclonal antibodies was used to identify, by indirect immunofluorescence, Colombian strain flagellates in cryostat sections or glass slide smears of the insect vector's intestine. PMID- 3329787 TI - The origin of espundia. PMID- 3329786 TI - Application of time-resolved fluoroimmunoassay (TR-FIA) for the diagnosis of invasive amoebiasis. AB - A development of solid-phase immunoassay, time-resolved fluoroimmunoassay (TR FIA), was used for anti-amoebic antibodies. The test used a chelate of the lanthanide europium as label. The long fluorescent life-time and large Stoke's shift of europium chelates permit sensitive detection in a time-resolved fluorimeter. The TR-FIA was compared with counterimmunoelectrophoresis (CIEP), indirect haemagglutination (IHA) and enzyme-linked immunosorbent assay (ELISA) using 61 sera from patients with invasive amoebiasis, 344 sera submitted routinely for amoebic serology without clinical data, 125 sera from patients with diseases other than amoebiasis, and 86 sera from "healthy" individuals. Overall agreement between TR-FIA and ELISA was 97.1%, between TR-FIA and IHA 93.2%, and between TR-FIA and CIEP 94.0%. Sensitivity, specificity and positive and negative predictive values were calculated to compare the 4 diagnostic methods in invasive amoebiasis. TR-FIA showed a higher validity than other methods. The application of such highly detectable labels in immunometric assays promises to open up entirely new areas of research. PMID- 3329788 TI - [Cimetidine in herpes zoster. A double-blind study in general practice]. PMID- 3329789 TI - [The influence of non-steroidal anti-inflammatory drugs (NSAID) in the treatment of peptic ulcer. A prospective randomized study]. PMID- 3329790 TI - [Partial mole with a fetus]. PMID- 3329791 TI - [Cefotetan, Apatef]. PMID- 3329792 TI - [Treatment of stage 2 supination-eversion ankle fractures]. PMID- 3329793 TI - [Prognostic evaluation of a patient with acute anuria]. PMID- 3329794 TI - [Mathematical determination of the growth curve parameters of BHK-21(C13) multiplying in suspension culture]. AB - A mathematical method for nomination of the continuity of the growing curve BHK 21(C13) phases, cultivated in the conditions of a one litre fermentor was used. The number of cell dividing (n), the speed of dividing (R) and the time of the entire dividing of the culture were calculated as well. It was established that the lowest point of the growing curve was in the 4th h and 34th min from the beginning of cultivation, the duration of the exponential phase is 20 h and 15 min. At the end of the exponential phase n is 1.85, Tg--12 h, 57 min and R- 0.077. The short lag-phase is explained with the three dimension cell multiplication. PMID- 3329795 TI - A correlative, immunocytochemical and cytological study of the two types of acidophils in the anterior lobe of the pituitary of the ram. PMID- 3329796 TI - Repair of UV-irradiated plasmid DNA in mutants of Saccharomyces cerevisiae and Escherichia coli deficient in repair of pyrimidine dimers. AB - The repair of in vitro UV-irradiated DNA of plasmid pBB29 was studied in excision defective yeast mutants rad1, rad2, rad3, rad4, rad10 and in Escherichia coli mutants uvr- and recA-, by measuring the cell transformation frequency. Rad2, rad3, rad4, and rad10 mutants could repair plasmid DNA despite their inability to repair nuclear DNA, whereas the reduced ability of rad1 mutant for plasmid DNA repair demonstrated alone the same dependence on the host functions that are needed for nuclear DNA repair. In E. coli the repair of UV-irradiated plasmid DNA is carried out only by the excision-repair system dependent on uvr genes. Treatment of UV-irradiated plasmid DNA with UV endonuclease from Micrococcus luteus greatly enhances the efficiency of transformation of E. coli uvr- mutants. Similar treatment with cell-free extracts of yeast rad1 mutant or wild-type strains as well as with nuclease BaL31, despite their ability for preferential cutting of UV damaged DNA, showed no influence on cell transformation. PMID- 3329797 TI - [The world's first successful autotransplantation of the heart for recurrent tumor]. PMID- 3329799 TI - Clinical and pathological aspects of severe malaria. PMID- 3329798 TI - DNA synthesis and genome structure of Plasmodium: a review. PMID- 3329800 TI - Sabin and Salk poliovirus vaccine: vice versa. PMID- 3329801 TI - [The estimation of fetal growth by ultrasound--the estimation of fetal body weight and fetal growth pattern based on fetal biparietal diameter, abdominal diameter and femur length]. PMID- 3329802 TI - [Studies on the synthesis of (E)-substituted phenylhydrazones of 1-aryl-2 imidazolyl and benzimidazolyl ethanone and their antifungal activity]. PMID- 3329803 TI - [Resolution of enantiomers and diastereoisomers by HPLC and its application in pharmaceutica analysis]. PMID- 3329804 TI - [Resolution of enantiomers and diastereoisomers by HPLC and its application in pharmaceutical analysis]. PMID- 3329805 TI - [Use of infra-red spectrometry in pharmaceutical analysis]. PMID- 3329806 TI - [Synthesis of trifluoromethyl amodiaquine analogs and antimalarial activity]. PMID- 3329807 TI - [Studies of the metabolism and pharmacokinetics of active principles isolated from Chinese herbal medicine since the founding of the People's Republic of China]. PMID- 3329808 TI - [Effects of 13 compounds on the activity of globinase and amounts of free amino acids in Plasmodium berghei]. PMID- 3329809 TI - New developments in the etiology and pathogenesis of bacterial vaginosis. AB - Bacterial vaginosis is unlike the "classic" sexually transmitted diseases. Unlike cervical infection with Chlamydia or salpingitis caused by N. gonorrhoeae, no single etiologic agent has been identified, and the organisms which are associated with infection have all been found as members of endogenous vaginal flora, with the possible exception of Mobiluncus species. If, as we suspect, BV is due to interactions among various organisms found in the vagina during vaginal health, we must determine what changes in the microbial or chemical ecology determine the development of BV. If, for instance, BV is simply due to an inversion in the concentrations of various organisms such that the anaerobes which are usually present in low numbers become predominant and the lactobacilli which usually predominate become few in number, we must determine which causes what. That is, does some organism or environmental change allow the anaerobes to overgrow and thereby inhibit the lactobacilli, or does some change inhibit the lactobacilli, thereby, allowing the other flora to overgrow? Answers to questions such as these await further research. PMID- 3329811 TI - Controversies in urinary tract infection. PMID- 3329812 TI - Murine models for studying the pathogenesis and treatment of pyelonephritis. PMID- 3329810 TI - Urinary tract infection. PMID- 3329813 TI - Uropathogenic Escherichia coli: molecular mechanisms of adherence. PMID- 3329814 TI - Laboratory aspects of chlamydial infections. PMID- 3329815 TI - Chlamydia trachomatis. PMID- 3329816 TI - Pathogenesis and significance of urogenital mycoplasmal infections. AB - U. urealyticum and M. hominis can no longer be considered as harmless commensals of the lower genitourinary tract. Both can produce disease in humans. Diagnosis and management of infections due to these organisms must be based upon isolation of the organisms from the affected site and preferably the number of organisms present. Due to the frequent resistance of both organisms to tetracycline, treatment must be based upon appropriate antibiotic sensitivities. For a more detailed description of the basic biology of these organisms and isolation and identification and treatment, the reader is referred to several recent reviews. PMID- 3329817 TI - [Role of microbiology laboratories in the monitoring of hospitals (antibiotics excepted)]. PMID- 3329818 TI - [Value of dapsone in the treatment of rhizomelic pseudopolyarthritis and Horton's disease]. AB - In 11 patients suffering from polymyalgia rheumatica or Horton's disease, dapsone was associated with corticotherapy because of corticosteroid side effects (11 cases) and/or progression of the disease despite relatively high dose steroid therapy (6 cases). This treatment had to be discontinued in 4 patients because of side effects and in 3 patients because of a recurrence of the disease. Despite these numerous withdrawals, dapsone seems to be of clinical benefit in these patients because of 1) the mildness of the side effects observed in this study, 2) its efficacy evaluated on the improvement of clinical signs of the disease and, overall, on the decrease in the corticosteroid consumption. PMID- 3329819 TI - [Nephrotoxicity of iodine contrast media]. PMID- 3329820 TI - [Blood and tumor eosinophilia associated with non-hematopoietic cancers: etiology, prognosis and physiopathology]. PMID- 3329821 TI - [Physiopathology of autoimmune endocrine diseases: current concepts]. PMID- 3329822 TI - [Leukocytoclasic vasculitis during treatment with low-dose captopril]. PMID- 3329823 TI - [Lupus syndrome in palmoplantar pustulosis]. PMID- 3329824 TI - [Renal insufficiency as a manifestation of lymphoma with acquired hypocomplementemia and Gougerot-Sjogren syndrome. Apropos of a case]. PMID- 3329825 TI - [Pulmonary manifestations of chickenpox. Apropos of a case. Review of the literature]. PMID- 3329826 TI - Monitoring and evaluating man-made mineral fibres: work of a WHO/EURO Reference Scheme. PMID- 3329828 TI - Proceedings of the meeting of the American Society for Stereotactic and Functional Neurosurgery. Montreal, Que., June 3-6, 1987. PMID- 3329829 TI - Future possibilities in stereotactic surgery: where are we going? PMID- 3329830 TI - Automated stereotactic positioning system. AB - An automated stereotactic machine has been interfaced to a surgical computer to complete a totally interactive surgical system capable of locating tumor volumes. Stepper motors, activated by the host computer, drive a three-dimensional slide to position the patient's head with respect to a fixed arc, locating the surgical target. Linear encoders on each axis create a closed-loop positioning system and a digital display for visual inspection of the slide's position. The 160-mm arc directs all instrumentation to its isocenter, regardless of the two angular settings, providing maximum freedom in selecting a safe trajectory to the target. Phantom test points compatible with computerized tomographic and magnetic resonance imaging were repeatedly scanned to determine the overall system accuracy, which approached 0.6 mm, depending on the spatial resolution of the image. This stereotactic device may be used to perform stereotactic laser craniotomies, biopsies, 192Ir implants for interstitial radiation, third ventriculostomies and functional procedures. PMID- 3329827 TI - Enteric immunization reveals a T cell network for IgA responses and suggests that humans possess a common mucosal immune system. AB - The local IgA response is a result of two related events, the induction of sensitized T and B cells in gut- or bronchial-associated lymphoreticular tissues (GALT or BALT) and the final differentiation of IgA plasma cells in mucosal tissues where IgA is produced and transported to become secretory IgA (S-IgA) antibodies into external secretions. Oral administration of various types of antigens/vaccines may result in two types of response, i.e., S-IgA antibodies at mucosa and systemic unresponsiveness to antigen, a state termed oral tolerance. Regulatory T cells in GALT help account for both S-IgA responses and oral tolerance and thus serve to fine tune responses to orally encountered antigens. Studies in animal models and humans have shown that oral administration of antigens sensitize lymphoid cells in GALT which subsequently home to mucosa and result in S-IgA responses in several external secretions. The significant promise of oral vaccines for prevention of microbial diseases including neisserial diseases is discussed. PMID- 3329831 TI - Computer-interactive stereotactic resection of deep-seated and centrally located intraaxial brain lesions. AB - The carbon dioxide laser has been incorporated into a computer-interactive stereotactic system for precision resection of deep-seated intraaxial neoplasma defined by stereotactic computed tomography and magnetic resonance imaging. One hundred and ninety-seven procedures were performed on 191 patients having deep seated lesions. Postoperative results have been satisfactory as regards the postoperative condition of the patient in consideration of the completeness of tumor removal achieved. PMID- 3329833 TI - Combined use of a new target-centered arc system with the BRW floor stand and phantom base for a wider range of approaches and applications in stereotaxy of the head and neck. AB - A unique target-centered arc system has been developed which combines the azimuth and declination angle approach concept of the standard BRW arc with the anteroposterior, lateral and vertical movements of the earlier Todd-Wells Guide for maximal versatility of image-guided stereotaxy. The arc system mounts on the BRW floor stand and provides completely unobstructed approaches to the upper hemisphere, base of the skull, posterior fossa or cervical region. It is ideally adapted for implant arrays and laser surgery. A new transferable phantom pointer affords target confirmation using the BRW phantom base. PMID- 3329832 TI - Helmet for infant skull fixation during stereotactic neurosurgery. AB - A thermoplastic helmet was designed to allow the use of the Leksell stereotactic frame in infants. PMID- 3329834 TI - The Brown-Roberts-Wells (BRW) arc: its concept as a spatial navigation system. AB - The Brown-Roberts-Wells (BRW) Arc System can be compared to spatial navigation because both utilize the concept of direction to and spatial location of a point in space by referencing to a horizontal angle (azimuth) and a vertical angle (declination) relative to the horizon. The BRW system also permits the determination of the distance from a reference surface of the arc system to the point (target). The methods of determining these parameters are explained in detail with illustrations. PMID- 3329835 TI - Experience with the Pelorus stereotactic system. AB - The Pelorus stereotactic system, by its unique approach, alleviates the need for the traditional head frame and computer-generated coordinates which are common to most other systems. Despite its simplicity, it sacrifices nothing in terms of the range of problems for which it can be used to diagnose and treat. In fact, its unencumbered design may make it more appropriate for advanced procedures than conventional systems. PMID- 3329836 TI - New diagnostic and therapeutic tools in stereotaxy. AB - A definitive pathoanatomic diagnosis was achieved in 14 biopsies of deep cerebral tumors in which the Laitinen CT adapter was utilized. In 5 patients, a third ventricular colloid cyst was aspirated or resected by stereotactic endoscopy, with excellent results after a mean follow-up time of 2.5 years. Several instruments, including a diagnostic ultrasound probe, an ultrasonic aspirator, a combination laser and an endoscope can be used stereotactically when mounted on a special instrument carrier. Integration of the Laitinen stereotactic device and the CT adapter was developed to allow noninvasive stereotactic radiotherapy in a conventional fractionation schedule by a standard linear accelerator. Technical experiences using this radiosurgical system in over 30 sessions for treating inoperable cerebral arteriovenous malformations are promising, but the follow-up time is too short for evaluating the clinical effect. PMID- 3329837 TI - Brown-Roberts-Wells stereotactic frame modifications to accomplish magnetic resonance imaging guidance in three planes. AB - The Brown-Roberts-Wells (BRW) computer tomography (CT) stereotactic guidance system has been modified to accommodate magnetic resonance imaging (MRI). A smaller head ring, which fits in standard MRI head coils, is constructed of a non ferromagnetic aluminum ring that is split to prevent eddy currents and anodized to prevent MRI image distortion and resolution degradation. A new localizing device has been designed in a box configuration, which allows BRW stereotactic coordinates to be calculated from coronal and sagittal MRI images, in addition to axial images. The system was tested utilizing a phantom and T1- and T2-weighted images. Using 5-mm MRI scan slices, targets were localized accurately to a 5-mm cube in three combined planes. Optimized calibration of both low field strength (0.3 T) and high field strength (1.5 T) MRI systems is necessary to obtain thin slice (5 mm) images with acceptable image resolution. To date, 10 patients have had MRI stereotactic localization of brain lesions that were better defined by MRI than CT. PMID- 3329838 TI - Computer-driven robot for stereotactic surgery connected to CT scan and magnetic resonance imaging. Technological design and preliminary results. PMID- 3329839 TI - MRI contribution to the stereotactic management of cerebral tumours. AB - Of 67 patients with cerebral tumours studied by MRI, 60 underwent stereotactic biopsy for histological diagnosis. The data from MRI were compared with those obtained from the CT scan with regard to the pathological diagnosis. The tumoural nature and extent of a lesion were better revealed by MRI. The single or multiple localization of the process was also seen better by MRI. Moreover, the sagittal plane views shown by MRI provide much more accurate target placement and probe guiding for an orthogonal stereotactic approach. Finally, a post-biopsy MRI can show the biopsy site in relation to the tumour better. PMID- 3329840 TI - Role of stereotactic biopsy in the surgical treatment of cerebral tumors. AB - Out of 664 intracranial tumors subjected to surgical procedures since 1980, 163 underwent stereobiopsy. On the basis of this experience, we devised a scheme to help decide whether and why stereobiopsy is advisable. PMID- 3329842 TI - Computer-assisted stereotactic biopsy of intracranial lesions. AB - The use of a computer program that allows the integration of stereotactically gathered CT, MRI and digital angiographic data in the planning of a biopsy trajectory is described. This system has been used to perform 447 stereotactic biopsies in 439 patients. Intracranial hemorrhages occurred in three patients; combined morbidity and mortality was less than 1%. Incorporation of angiographic data and visualization of the surgical trajectory enhances the safety and accuracy of stereotactic biopsy of intracranial lesions. PMID- 3329841 TI - Thalamic abscess: a stereotactically treatable lesion. AB - A 69-year-old man developed abdominal pain, fever, shaking chills and acute hemiplegia. Computed tomography (CT) scanning demonstrated a hematoma within a thalamic space-occupying lesion having the radiological characteristics of a malignant glioma. Low-grade fever and leukocytosis persisted and follow-up CT scanning showed ring enhancement of the thalamic lesion and ependymitis suggesting a cerebral abscess. Stereotactic aspiration achieved drainage of the abscess and relief of mass effect and provided pus from which a causative organism was identified and treated with appropriate antibiotics. Contrast enhanced CT scan should be obtained in cases of hemorrhage within mass lesions and tissue diagnosis should be achieved even in deep brain regions, as this can be accomplished safely using stereotactic techniques. PMID- 3329843 TI - Stereotactic biopsy for deep-seated intracerebral lesions. Correlation between computer tomography, positron emission tomography and electrophysiological activity. AB - In 16 cases of stereotactic deep brain biopsy, a correlative study was made by computer tomography, positron emission tomography, and electrophysiological depth recording. This multimodal study is shown to be of great value in stereotactic biopsy of deep-seated cerebral lesions. PMID- 3329844 TI - Technique of stereotactic biopsy of two cranial target employing spherical coordinates to define a single trajectory. AB - A 'spherical coordinate system' has been developed to allow either stereotactic biopsy of two intracranial lesions using a single predetermined trajectory or biopsy of a single lesion through an existing burr hole. By means of the Gildenberg technique, the CT coordinates of the targets (or target and burr hole) are obtained. These are employed in three simple trigonometric equations to give three coordinates-two angles for the probe carrier (theta and alpha) and the radius (T) of a sphere, defined by one target as the center and the other target on the surface. These can be utilized in the Todd-Wells stereotactic frame. This system was evaluated using hollow skulls and crossed 30-gauge wire for phantom targets. The system was tried on ten different target combinations, and eight successful trajectories were obtained to within 3 mm. Two target combinations were inaccessible because of technical limitations of the Todd-Wells frame. This 'spherical coordinate system' can decrease the time to localize multiple targets as well as minimize the number of passes. PMID- 3329847 TI - CT-guided stereotactic biopsies of lesions in the medulla and a case of Leigh's disease. AB - CT-guided stereotactic biopsy of lower brain stem lesions in 7 consecutive cases is discussed. A frontal transincisural approach was used. Five patients had astrocytomas histologically. The single patient who had undergone empirical radiation therapy prior to tissue diagnosis revealed only necrosis. One patient was found to have pathology suggestive of Leigh's disease. This patient was not radiated and is the first alive adult to have this diagnosis confirmed. Although controversy still exists in the management of brain stem lesions, we intend to demonstrate the value of tissue diagnosis in the management of such lesions. PMID- 3329845 TI - Neural noise as a real time guide for tumor site verification during stereotactic biopsy of brain tumors. AB - Neural noise has been successfully used as a real time guide for verification of tumor site during stereotactic biopsy of brain tumors. This technique is a useful adjunct to other methods for tumor site verification and may possibly give pathophysiological information in peritumoral areas. PMID- 3329846 TI - Stereotactic approach to space-occupying lesions in the posterior fossa. PMID- 3329849 TI - Stereotactic brain biopsies in presenile dementia. AB - Early detection and precise diagnosis of presenile dementias are important since they determine subsequent medical care. Presently the only way to classify these syndromes is by neuropathological examination. Between 1972 and 1987, 222 stereotactic serial brain biopsies were performed in 25 selected demented patients. Comparison between preoperative clinical diagnosis and histological finding gives the following results: in 32% the clinical diagnosis has been confirmed, in 60% the diagnosis has been corrected or specified and in 8% the stereotactic brain biopsies only showed unspecific pathological gliosis. PMID- 3329848 TI - Stereotactic aspiration of colloid cysts of the third ventricle. Preliminary report. AB - From January, 1979, to July, 1986, 10 patients (6 females, 4 males; 12-59 years, mean 37) with colloid cysts of the third ventricle were treated by stereotactic aspiration (Talairach's method). Five cysts have been completely aspirated. The mean residual volume of the other 5 was 19% of the initial volume. Clinical symptoms completely cleared in all but one patient. The advantages of the procedure are discussed. PMID- 3329850 TI - Stereotactic administration of intratumoral chronic chemotherapy of recurrent malignant gliomas. AB - There is a continuous search for more efficient treatment of malignant cerebral gliomas. The work of Penn and Croin demonstrates clearly that survival of rats having experimental gliomas is significantly increased by intratumoral chemotherapy. It has been shown that chronic depth electrodes for the investigation of epileptic patients is a reliable and safe method. Using this proven technology originally developed by Talairach, Szikla and co-workers we have developed catheters for intratumoral chemotherapy. Three patients have been treated. It is premature to pretend that this is a treatment which will lengthen the patient's life. Nevertheless, the feasibility of the technique, its precision and safety are assured. Following this course of treatment, we have seen no deteriorations, no side effects, no bone marrow depressions, and no sign of toxicity. Chemical analysis has shown that cisplatin was delivered to the tumor. PMID- 3329851 TI - Sedation for stereotactic headframe application: a randomized comparison of two techniques. AB - A prospective, randomized study was performed in 87 patients to compare the safety, efficacy and dose requirements of two sedation techniques for stereotactic headframe application. Sedation administration and headframe application averaged 30 min. Fifty patients weighing 76 +/- 13 kg (mean +/- SD) received mean doses of 154 micrograms fentanyl plus 5.5 mg droperidol i.v. (FD group). An additional 37 patients weighing 76 +/- 19 kg received mean doses of 127 micrograms fentanyl plus 6.7 mg Valium (diazepam; FV group). Both treatments provided excellent hemodynamic stability and a low incidence of adverse side effects while providing adequate analgesia and sedation. The incidence of anesthetist-assessed patient anxiety and discomfort was more favorable in the FD group. PMID- 3329853 TI - Danger of use of hydrogen peroxide in stereotactic biopsies. PMID- 3329852 TI - CT-controlled stereotactic aspiration in hypertensive brain hemorrhage. Six-month postoperative outcome. AB - CT-guided stereotactic aspiration surgery for the evacuation of hypertensive brain hemorrhage (HBH) has been introduced recently. From December, 1980, to April, 1986, we used aspiration surgery in 375 cases of HBH. The 6-month postoperative outcome of aspiration surgery for acute basal-ganglionic hemorrhage was compared with that after conventional surgery of all Japan and those after conservative treatment. In basal-ganglionic hemorrhage, aspiration surgery led to a favorable clinical experience and outcome, providing the possibility of a new avenue of surgical treatment of HBH. PMID- 3329854 TI - Preoperative stereotactic localization of cerebral tumors: a new tool to improve microsurgical tumor removal. PMID- 3329855 TI - Stereotaxy and thalamic masses. Survey of 44 cases. AB - Thalamic masses are generally considered inoperable; little is known of the precise nature of these lesions. Stereotactic biopsy was performed in 44 patients, with no mortality and low morbidity (only 1 case of transitory hemiparesis). The stereotactic biopsy (minimum 5 specimens taken along the major axis of the lesion) showed that the majority of the young patients (less than 40 years) had low-grade glial neoplasms (grade I-II astrocytomas or oligodendrogliomas), while in older patients highly malignant tumors prevailed. Beside the neoplasms in the children and adults, we found granulomas, abscesses, infarcts, hemorrhages and glioses. Present neuroradiological methods cannot establish a final correct diagnosis in thalamic lesions, so stereotactic biopsy is recommended. A follow-up of 1-6 years is presented for 7 patients who underwent stereotactic 125I brachytherapy. PMID- 3329856 TI - Stereotactic heavy-particle irradiation of intracranial arteriovenous malformations. AB - Stereotactic irradiation appears to be effective in causing partial or complete thrombosis of AVM that are not surgically resectable. Use of heavy particles generated in a cyclotron allows better spatial definition and dose distribution than do other methods, allowing larger AVM to be treated. From these preliminary results, it is evident that heavy-particle irradiation therapy, like proton beam therapy, does not offer protection from recurrent hemorrhage for at least 12 months, nor is it devoid of major complications; it does offer a noninvasive mode of therapy for AVM that are difficult to treat surgically, however. PMID- 3329857 TI - First United States 201 source cobalt-60 gamma unit for radiosurgery. AB - Installation of the first United States 201-source 60Co gamma unit for stereotactic radiosurgery was completed at the University of Pittsburgh in May, 1987. Despite a very favorable 19-year experience in Stockholm, introduction of this technology into the US proved to be a formidable task. Extensive internal and government regulatory review by the Health Systems Agency, the Food and Drug Administration and the Nuclear Regulatory Commission ultimately resulted in approval of marketing and use of the gamma unit. Clinical use and radiobiological research has begun. PMID- 3329859 TI - Treatment of arteriovenous malformations with the linear accelerator. PMID- 3329858 TI - Linear accelerator radiosurgery of arteriovenous malformations. AB - Forty-five patients affected by cerebral arteriovenous malformations not suitable to open surgery have been treated by a radiosurgical technique employing a linear accelerator. One-year follow-up angiography is available for 10 cases. Therapeutic effect of focalized irradiation is presented. PMID- 3329861 TI - Stereotactic external beam calculations for radiosurgical treatment of brain lesions. AB - Radiosurgical techniques are becoming increasingly popular for the selective destruction of brain lesions. To ensure precision in the procedure, set-up and treatment of lesions in this manner, we have adopted standard stereotactic methods to allow one to calculate accurately the absorbed dose and also to preserve accuracy in locating the target site in three dimensions. At McGill University, radiosurgery is performed using the dynamic technique, which utilizes the concurrent rotation of both the 10-MV photon beam linear accelerator (from 30 to 330 degrees) and the patient couch (from 75 to -75 degrees) about a common point centered on the target within the lesion. A three-dimensional treatment planning system for the calculation of dose distributions implemented in conjunction with CT, MRI and DSA stereotactic image analysis systems is presented. PMID- 3329860 TI - Physical aspects of dynamic stereotactic radiosurgery. AB - Dynamic stereotactic radiosurgery is a radiosurgical technique based on a medium energy isocentric linear accelerator and a stereotactic frame. The technique uses concurrent and continuous rotations of both the gantry (300 degrees, from 30 to 330 degrees) and the couch (150 degrees, from 75 to -75 degrees). It gives a uniform dose (+/- 5%) within the target volume and dose fall-offs outside the target volume comparable to those obtained from presently known radiosurgical techniques. PMID- 3329863 TI - Removable, adjustable and reusable implants for stereotactic interstitial radiosurgery of brain tumors. AB - Sixty primary brain tumors (gliomas) were treated by interstitial radiosurgery using 192Ir according to a protocol based on the size of the tumor. In all cases, the radioactive wires were left in place for periods ranging from 5 to 10 days, according to dosimetry calculations, and then removed, which was made possible by the use of removable implants. The stainless steel tubes are occluded on their inner side and adjustable in length depending on the depth of the tumor, and are introduced through screws inserted into the skull in an array depending on the preliminary dosimetry. The tubes were afterloaded with 192Ir and removed at the end of the calculated time. Forty-six patients (18 low-grade and 28 malignant gliomas) were treated using this method. One small hematoma was evacuated and no sepsis occurred. PMID- 3329864 TI - Multiplanar CT-guided stereotaxis and 125I interstitial radiotherapy. Image guided tumor volume assessment, planning, dosimetric calculations, stereotactic biopsy and implantation of removable catheters. AB - A method using Multiplanar CT-guided stereotactic biopsy and high-dose 125I interstitial radiotherapy in patients with malignant nonresectable or recurrent brain tumors is presented. Optimal interstitial radiotherapy requires careful preoperative planning, computer-assisted dosimetry, CT-guided stereotactic biopsy and implantation of catheters that will be loaded with 125I seeds. A method is presented by which the isodose curve distribution is adjusted to the tumor size, volume and axis, allowing treatment of the imaged and histologically determined border of the tumor with 60 Gy at a dose rate of 40 rad/h. PMID- 3329862 TI - Single-scan stereotactic tumor biopsy and brachytherapy. AB - Stereotactic tumor biopsy and brachytherapy catheter implantation can be accomplished with targets derived from computed axial tomography and magnetic resonance scans. Computer manipulation of image data allows both diagnostic and therapeutic procedures to be carried out from a single set of scan slices. This eliminates the need for repeat scanning as part of the surgical procedure. Microcomputer technology is sufficiently advanced to handle the images and graphics necessary for stereotactic neurosurgery. A system based on the IBM PC/AT designed for this purpose uses readily available graphics software and custom designed imaging programs. Direct loading of computed axial or magnetic resonance scan images from magnetic tape can be accomplished. Determination of points, contours and volumes in three-dimensional space allows intraoperative alignment of image data and patient landmarks within the stereotactic head frame using pattern recognition overlays. Three-axis scaling for magnification correction along with rotational and linear data transformations provide the basis for single-scan stereotaxis. Interactive computer graphics integrate image, patient and frame coordinates for target determination. This method eliminates the need to design and fabricate nonmagnetic or radiolucent scanner-compatible devices. PMID- 3329865 TI - Iridium-192 brachytherapy in combination with interstitial microwave-induced hyperthermia for malignant glioma. AB - A phase I clinical trial assessing the feasibility and safety of hyperthermia in combination with 192Ir brachytherapy (60 Gy) for the treatment of malignant glioma now includes 14 patients. Hyperthermia (42-43 degrees C at tumor margin for 60 min) has been induced using stereotactically implanted afterloading catheters and a microwave (915 or 2,450 MHz) antenna array. Thermometry recorded along each catheter confirms the general ability of the technique to heat such volumes, but thermal heterogeneities are documented. Transient or permanent worsening of previous neurologic deficit, seen in 7 patients, has been the most common morbidity. PMID- 3329866 TI - Interstitial radiation in recurrent malignant gliomas. AB - Twelve patients with recurrent supratentorial gliomas were treated with implanted 125I seeds. The interval from initial surgery to interstitial radiation ranged from 3 months to 9 years. The techniques for brachytherapy included volume implantation by craniotomy in one, stereotactic implantation with low-activity seeds in 7 and high-activity seeds in 4 patients. The total dose received ranged from 5,500 to 27,000 cGy. CT scans performed sequentially on all patients showed progressive attenuation in areas previously enhancing, suggestive of tumor necrosis produced by the interstitial sources. The mean and median survival of these patients was 23 and 22 weeks, with the 4 most recent patients still alive. PMID- 3329867 TI - Choice of radioisotope in stereotactic interstitial radiotherapy of small brain tumors. AB - In stereotactic interstitial radiotherapy, small radioactive sources are placed within the brain tumor to deliver locally high radiation doses. The choice of the radioisotope depends upon the dose distribution around the isotope, energy of the emitted radiation, relative biological effectiveness, and finally, the cost and availability of the isotope. We have analyzed 198gold, 125iodine and 192iridium in terms of these four factors. Our results have shown that 125I is superior to the other two isotopes due to its soft X-rays and dosimetric as well as radiobiological properties. Unfortunately, it is the most expensive of these radioisotopes, and can be difficult to obtain in specific activities. PMID- 3329868 TI - Late considerations in the treatment of low-grade malignancy cerebral tumors with iodine-125 brachytherapy. AB - The authors report their series of 45 patients harboring inoperable, low-grade cerebral neoplasms, treated in the past 6 years with 125I stereotactic brachytherapy. The majority of these tumors were grade I and II astrocytomas and oligodendrogliomas (82.2%). A 2.6- to 6-year follow-up shows good results in 65.6% with reduction or disappearance of the lesions on CT images and good social reentry. Nine patients (23.7%) died prior to follow-up. Young patients (less than 40 years) responded well to interstitial radiotherapy, while patients over 40 with the same histological findings of low-grade tumors responded poorly to this type of treatment. Diffuse infiltrating cortico-subcortical tumors, optochiasmatic gliomas, hypothalamic and lower brainstem neoplasms do not respond satisfactorily to 125I radioisotope implantations. PMID- 3329869 TI - Normal brain irradiation during stereotactic brain implants using radioactive iodine-125. AB - Stereotactic interstitial brain implants deliver locally high radiation doses to treat malignant gliomas. Dose to the surrounding normal brain from an 125I implant has been compared with the dose from an external irradiation technique. Results show that an implant offers a higher dose gradient around the tumor and hence a lower dose to the normal brain. Moreover, some irregular-shaped tumors, while ideal for a stereotactic implant, may be very difficult to treat with external beams without delivering a significant radiation dose to the normal brain. An implant seems to be dosimetrically superior to external irradiation for delivering large tumor doses. PMID- 3329871 TI - Long-term follow-up study of nucleus ventralis intermedius and ventrolateralis thalamotomy using a microelectrode technique in parkinsonism. AB - Long-term observation over 3-8 postoperative years of cases of Parkinson disease operated by stereotactic thalamotomy using a microelectrode recording technique is reported. The procedure is specifically useful in the following four groups: (1) tremor-dominant cases, (2) hemiparkinsonism, (3) cases with marked asymmetry in motor symptoms and (4) juvenile parkinsonism presenting levodopa-induced dyskinesia. PMID- 3329870 TI - Stereotactic surgical planning with magnetic resonance imaging, digital subtraction angiography and computed tomography. AB - Over the past 2 years at the Montreal Neurological Institute and Hospital, we have evolved an integrated environment for the planning of stereotactic procedures, based on images from magnetic resonance imaging, digital subtraction angiography and computed tomography modalities. These procedures rely on fiducial marker sets which are attached to our 'OBT' stereotactic frame, and which may be recognized in the images. The software package is modular and operates in both minicomputer (PDP-11 and VAX) and IBM personal computer environments. In addition to routine tasks for stereotactic planning, the package also supports dosimetry planning for stereotactic radiosurgery. PMID- 3329872 TI - Selection of the optimal lesion site for the relief of parkinsonian tremor on the basis of spectral analysis of neuronal firing patterns. AB - Techniques for quantitatively describing the firing properties of neurons have been used to identify thalamic cells with a firing pattern which is correlated with EMG activity during tremor. By locating these cells relative to the anterior border of the somatosensory nucleus and the anterior commissure-posterior commissure line, it may be possible to select the optimal lesion site for the relief of parkinsonian tremor on a rational rather than an empirical basis. PMID- 3329873 TI - Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. AB - Stereotactic thalamotomy of the thalamic nucleus ventralis intermedius (VIM) is routinely used for movement disorders. During this procedure, it has been observed that high-frequency (100 Hz) stimulation of VIM was able to stop the extrapyramidal tremor. In patients with bilateral tremor of extrapyramidal origin, who were resistant to drug therapy, the therapeutic protocol associated (1) a radiofrequency VIM thalamotomy for the most disabled side, and (2) a continuous VIM stimulation for the other side using stereotactically implanted electrodes, connected to subcutaneous stimulators. VIM thalamotomy relieved the tremor in all operated cases. Side effects were mild and regressive. VIM stimulation strongly decreased the tremor but failed to suppress it as completely as thalamotomy did. This was due in part to the fact that programmable stimulator frequency rate is limited to 130 Hz, while it appeared that the optimal stimulation frequency was 200 Hz. This therapeutic protocol appears to be of interest for patients with bilateral extrapyramidal movement disorders. PMID- 3329874 TI - Wilder Penfield (1891-1976). A protagonist for functional neurosurgery. PMID- 3329876 TI - Analysis of a four-year experience with depth electrodes and a two-year experience with subdural electrodes in the evaluation of ablative seizure surgery candidates. AB - Chronically implanted depth and subdural electrodes have both been shown to be satisfactory means of localizing epileptogenic foci. Utilizing bilateral mesial temporal depth electrodes, we have localized mesial temporal foci in a large percentage of patients. Depth electrode investigation of a more limited number of patients with suspected extramesial temporal foci has not been as reliable in giving localizing information. We have more recently used subdural electrodes to investigate this latter category of patients, and preliminary findings suggest that this technique may be of localizing value in several subcategories. PMID- 3329875 TI - Magnetic resonance imaging in the assessment and surgical management of epilepsy and functional neurological disorders. AB - Magnetic resonance imaging (MRI) offers significant advantages over computerized tomography (CT) and teleradiographic techniques when used for the evaluation and management of epilepsy and functional neurological disorders. Depth recording and radiofrequency electrodes can be more accurately positioned within structures such as the amygdala and hippocampus. The extent of corpus callosum section, lobectomy, topectomy, and radiofrequency stereotactic lesions can now be readily confirmed and related with seizure, neurological, and behavioral outcome. Occult, usually low grade, intraparenchymal neoplasms not visualized on CT scans can be located by MRI and biopsied or excised by MRI stereotactic techniques. PMID- 3329877 TI - Thalamic microelectrode recording and microstimulation in central and deafferentation pain. AB - Microelectrode recording and microstimulation (in 1 case macrostimulation) were used to localize stereotactic targets in 8 patients with central and deafferentation pain and 1 'deafferented control' patient without pain. Off-line study revealed two features commonly proposed as potential physiological factors for such pain, but they were present in both pain and control patients- somatotopographic reorganization and the presence of bursting cells. In all patients in whom stimulation induced pain referred to deafferented parts of the contralateral body, hyperpathia or allodynia were present instead of normal paraesthetic, sensorimotor or thermal responses. PMID- 3329878 TI - Effects of stereotactically applied neuromodulators on the deafferentation syndrome in rats. PMID- 3329879 TI - Creation of a three-dimensional atlas by interpolation from Schaltenbrand Bailey's atlas. AB - A 0.5-mm step atlas was interpolated from Schaltenbrand-Bailey's atlas. By serial display of the atlas with the desired rotation on a three-dimensional axis, a three-dimensional atlas was created. The newly created atlas can be used for computer-processed stereotactic data display. Any three-dimensionally located point can be displayed within 0.25 mm distance from the point, and spatial understanding of anatomical structures and stereotactic data is facilitated by the three-dimensional display. PMID- 3329880 TI - Thalamic functional tuning of the cortex in dichotic listening tasks. AB - In dichotic listening tasks, the (dominant) right ear's superiority in processing verbal stimuli has been attributed to its direct access to the linguistically dominant left hemisphere. The roles played by the extralinguistic factors, such as induced attentiveness and functional tuning of the auditory system, have not been carefully examined. The evidence for the facilitating effects of subcortical stimulation on processing dichotic stimuli is presented. PMID- 3329881 TI - Electrophysiological characterization of human subcortical structures by frequency spectrum analysis of neural noise (field potential) obtained during stereotactic surgery. PMID- 3329882 TI - Microcomputer stereotactic atlas. AB - A stereotactic atlas to determine thalamic target sites has been incorporated into a microcomputer. Variability studies of the thalamus with mean and standard deviations of nuclear borders are depicted graphically for overlay onto operative images. Internal landmarks traditionally used to reference target points for functional stereotaxis may be determined by conventional ventriculography or derived from magnetic resonance scans. Modeling of polyline vertices established from gray scale contour mapping and atlas reconstructions further enhance the spatial understanding of relationships to midline structures. Computer integration of anatomic reference points, graphically depicted images and stereotactic atlas data into head frame coordinates can be accomplished. This method is consistent with established stereotactic techniques and allows the visual conceptualization of imaged and graphic data for functional stereotaxis. PMID- 3329883 TI - Factors affecting measurements in computed-tomography-guided stereotactic procedures. PMID- 3329884 TI - Magnetic resonance imaging stereotaxy: recognition and utilization of the commissures. AB - Magnetic Resonance Imaging (MRI) offers a non-invasive method to visualize the intracerebral structures. Coupled to a compatible stereotactic frame and software, MRI can be used to determine the coordinates of intracranial targets. Coordinates of the anterior commissure, posterior commissure, targets and intercommissural distance were obtained from positive contrast ventriculography and by MRI in 6 patients undergoing stereotactic localization prior to the implantation of stimulating thalamic electrodes for pain control. The correlation of coordinates and measurements obtained with ventriculography and MRI is +/- 1 mm in most measurements, but up to 3 mm in 2 cases. Magnetic resonance stereotaxy allows non-invasive and precise localization of intracerebral targets, but does not yet allow its routine use with confidence. Further understanding of distortion and artifacts and corrections of these is mandatory. PMID- 3329885 TI - Stereotactic-computerized tomography interface device. AB - A mechanical stereotactic-computerized tomography interface device (SCID) is attached to the head at three bony fixation points and, after rigid fixation to the scanning gantry, is zeroed to make scan and stereotactic space identical. The system is simple, reproducible, accurate and reliable and has been used for tumour and excisional biopsy, radiation planning and instillation of radioisotopes. PMID- 3329886 TI - Multi-purpose stereoadapter. AB - A noninvasive adapter for CT-, MRI- and angiography-guided stereotaxis had originally been developed for morphological (tumor biopsy) surgery. Because of its high accuracy it has also been used for functional stereotaxis (e.g., thalamotomy, cingulotomy, hypothalamotomy, dentatotomy) and for external stereotactic irradiation of brain tumors and arteriovenous malformations with a conventional linear accelerator. Additionally, it has been used for locating subcortical brain tumors for open surgery. Recently, the adapter, supplied with a phantom base, has been used for percutaneous tumor biopsy and ventriculostomy without a stereotactic frame. PMID- 3329887 TI - Three-dimensional reconstruction of neuroradiological data within a stereotactic frame of reference for surgery of visible targets. AB - Three-dimensional information obtained with neuroradiological exams performed under stereotactic conditions is displayed on a surgical console within the graphic reconstruction of the geometry of stereotactic frames. Planning of convenient probe trajectories can be carried out taking into account all data derived from different diagnostic techniques. PMID- 3329888 TI - Animal research stereotactic instrument modified for computed tomographic guidance. AB - While target localization for human stereotactic surgery has been refined by computed tomographic (CT) and magnetic resonance imaging (MRI), stereotaxis in experimental animals has remained dependent upon external cranial landmarks and standardized atlas coordinates. To overcome the limitations and inaccuracies of animal devices using the original Horsley-Clarke method, we modified a standard animal stereotactic instrument in order to make target localization and coordinate determination possible with CT imaging. Although the device can be adapted to any medium-sized animal species, we demonstrate its use with dogs here. PMID- 3329889 TI - Angiographic localizer for the BRW stereotactic system. AB - Preliminary experience with a newly constructed angiographic localizer system for use in stereotactic neurosurgery is reported. This localizer ring, mounted on the BRW head ring, allows for the transformation of target points with known stereotactic coordinates (e.g., visible on computerized tomography scans) onto angiograms, as well as the determination of stereotactic coordinates of a set of points (e.g., arteriovenous malformations) indicated on at least two angiograms. PMID- 3329890 TI - The impact of computer and imaging technology on stereotactic surgery. AB - Computers, particularly medical imaging techniques, have created a renaissance in stereotactic surgery. Human stereotaxis was primarily developed and performed beginning in the 1940s for functional disorders. Interest waned in the 1960s following the introduction of L-dopa until computer-based three-dimensionally precise tomographic modalities (specifically computed tomography) were introduced beginning in the mid-1970s as a routine diagnostic aid. New image-compatible hardware and instrumentation were introduced along with techniques and associated software for relating points and volumes appearing on these diagnostic images into stereotactic space. This paper reviews the computer and imaging technology that has led to this renaissance and discusses some of the important features of a computer-interactive stereotactic system. PMID- 3329891 TI - Combined use of digital subtraction angiography and MRI for radiosurgery and stereoencephalography. AB - The authors report their experience with the combined use of digital subtraction angiography (DSA) and magnetic resonance imaging (MRI) for the stereotactic placement of intracerebral electrodes in epilepsy and for the radiosurgical treatment of otherwise inoperable arteriovenous malformations of the brain. Both imaging techniques, when used in conjunction, have been found most useful and complementary. For deep electrode placement, they permit optimal visualization of the cerebral structures to be reached by the electrode array while allowing the avoidance of vessels in the vicinity. For radiosurgery of arteriovenous malformations, DSA provides optimal visualization of the feeders and of the malformation itself, while the MRI reveals the cerebral structures to be spared by the photon beam of the linear accelerator. A discussion of their respective roles is presented, with the specific question as to whether MRI alone could be used for both procedures. PMID- 3329892 TI - [Immunopathology of rejection in human heart transplantations]. PMID- 3329894 TI - [Pulmonary arterial hypertension in decompensated cardiopathies. Prognostic implications after heart transplantation. Anatomo-clinical correlates]. PMID- 3329893 TI - [Detection of chronic rejection by endomyocardial biopsy in heart transplant patients. Contribution of immunofluorescence and electron microscopy]. PMID- 3329895 TI - [Carcinoid tumor of the breast. Apropos of a case with immunohistochemical and ultrastructural study]. PMID- 3329896 TI - [Morphometric and statistical study of the presence of myocardial bridges over the anterior intraventricular branch (anterior descending) of the left coronary artery in Brazilian subjects]. PMID- 3329897 TI - [Heart and the regulation of body fluids]. PMID- 3329898 TI - [Use of buspirone in cardiac neurosis]. PMID- 3329899 TI - [Intralobar pulmonary sequestration. Report of a case and review of the literature]. PMID- 3329900 TI - [Mitral valve prolapse]. PMID- 3329901 TI - [Criteria for cardiac catheterization and surgical intervention in aortic stenosis]. PMID- 3329903 TI - Increased release of prostacyclin-like activity from rat aorta by plasma from patients with hepatic or renal failure. AB - Exhausted rat aorta slices were incubated for 20 minutes at room temperature with plasma from 6 uremic patients undergoing maintenance hemodialysis, from 23 patients with hepatic disorders and with plasma from healthy volunteers. We observed that plasma from uremic as well as from patients with liver dysfunction stimulated prostacyclin release more than the simultaneously studied normal plasmas. Enhanced prostacyclin release may play a role in the pathogenesis of the hemorrhagic diathesis of patients with renal or hepatic failure. PMID- 3329904 TI - [Acute emphysematous cholecystitis. Report of a case and review of the literature]. AB - The authors report a case of acute emphysematous cholecystitis (AEC) operated on at the University Hospital of ABC Medical School (Sao Paulo), with a review of the literature. The infrequency of this finding and the participation of local ischemic factors, associated with secondary infection by gas forming bacteria are pointed out. The authors emphasize the importance of considering this entity potentially more severe than acute non-emphysematous cholecystitis (AnEC) because in AEC gallbladder gangrene is 30 times higher and perforation occurs 5 times more frequently than in AnEC. Besides, the patient with AEC may shows no clinical signs of severity, as in the case reported, where gallbladder gangrene was seen at surgery. In AEC, diagnosis is established usually when the plain abdominal X ray shows gas within the gallbladder or in its walls. The best results are obtained with cholecystectomy and antibiotic therapy. PMID- 3329902 TI - [Campylobacter pyloric, chronic gastritis, gastric ulcer and duodenal ulcer]. AB - After the initial report of Marshall and Warren, several publications have also demonstrated the presence of pyloric campylobacter in an elevated percentage of cases of chronic gastritis and peptic ulcer. We present our experience studying 672 patients examined by esophagogastroduodenoscopy after referral to clinical because of upper gastrointestinal symptoms. We used an Olympus GIF-K2 panendoscope taking two biopsies from the gastric antrum. Specimens were stained with hematoxilin-eosin and silver. In our experience these methods have given us the best results in detecting this bacteria. Diagnosis of gastric and duodenal ulcer was made by endoscopic criteria and chronic gastritis diagnosed by histology. Chronic gastritis was categorized into active and inactive based in the invasion of polymorphonuclear into mucosa. We have also quantitated damage of the mucin producing cells as well as the degree of bacterial colonization. We have found pyloric campylobacter in 91.8% of patients suffering from chronic active gastritis, 72.7% of patients with diagnosis of gastric ulcer and 84.2% of cases of duodenal ulcer. Our results agree with the ones reported by other authors. We conclude that pyloric campylobacter is not an opportunist microorganism within the stomach because it produces inflammatory changes as well as damage of the mucin producing cells. Its presence may play some role in the etiology of gastritis and peptic ulcer disease. PMID- 3329905 TI - [Research on enteropathogenic bacteria from children with acute diarrhea, in Belo Horizonte, MG]. AB - Enteropathogenic bacteria were searched in feces of 80 children with acute diarrhea from the lower social economical level, all of them younger than twenty seven months old, and without any antimicrobial therapy, in Belo Horizonte, MG, Brazil, from June 1981 to August 1982. The following enteropathogenic bacteria were isolated from 46 children: Shigella in 12 children (15.00%), enterotoxigenic Escherichia coli in 12 children (15.00%), classic enteropathogenic Escherichia coli in 9 children (11.25%), Salmonella in 6 children (7.50%). Association of enteropathogenic bacteria were found in 7 children (8.75%). Yersinia enterocolitica and invasive Escherichia coli were not isolated from any patient. PMID- 3329906 TI - Genetic control of NADH dehydrogenase-1 and aromatic alcohol dehydrogenase-2 in hexaploid wheat. AB - The genetic control of NADH dehydrogenase-1 (NDH-1) and aromatic alcohol dehydrogenase-2 (AADH-2) was investigated in Triticum aestivum cv. Chinese Spring. Evidence was obtained that NDH-1 is active as a monomer and is encoded by genes located in the p arms of the homoeologous group 4 chromosomes. The NDH-1 gene loci located in 4Ap, 4Bp, and 4Dp were designated Ndh-A1, Ndh-B1, and Ndh D1, respectively. Aadh-A2 was previously reported to be located in 6Aq; in this study, Aadh-B2 and Aadh-D2 were localized in 6Bq and 6Dq, respectively. Alcohol dehydrogenase-1 is expressed on AADH-2 zymograms; the presence of a contaminating aliphatic alcohol in one or more reagents is suggested as the probable cause of this phenomenon. PMID- 3329907 TI - Inheritance of soybean endopeptidase. PMID- 3329908 TI - [Fluoroimmunologic analysis of proteins]. AB - Review contains new data on protein fluoroimmunoassay (FIA), which combines advantages of RIA and EIA. Basic approaches to antibody production, principles of homogeneous and heterogeneous FIA as well as of time-resolved FIA properties of 28 fluorescent labels presenting various classes of organic compounds (of which most prospective are aminoquinolone, cyanocoumarines, chlorophylls, phycobiliproteins, metallorganic compounds) are described. Some examples of FIA application for quantitative evaluation of proteins in biological samples, properties of some FIA kits, and specifications of 6 fluorimeters developed for FIA are given. The nearest perspectives of FIA development and application in medical and biological research are considered. PMID- 3329910 TI - Prediction of protein structure from amino acid sequence. AB - Methods of predicting protein conformation from amino acid sequence are reviewed. Several widely used algorithms to predict local secondary structure are first discussed. Four general approaches to predict the tertiary structure are then described: (1) energy calculations from an open chain; (2) recognition of sequence homology with a known structure; (3) uses of a sequence template that dictates a particular fold; (4) docking alpha-helices and beta-strands. Throughout this review, the likely success of these methods is considered. PMID- 3329909 TI - [Primary structure of DNA complementary to mRNA of murine oncoprotein p53]. AB - Nucleotide sequencing of cDNA clone specific for murine oncoprotein p53 from the SVTZ all line has revealed nucleotide changes as compared with previously published structures of p53 cDNA originated from other cell lines. PMID- 3329911 TI - Iron and haem complexation studies of 2,3-dihydro-1H-imidazo(1,2-b)pyrazole (IMPY, NSC 51143), a tumour cell ribonucleotide reductase inhibitor. AB - Spectrophotometric studies have been undertaken of the interaction of various iron-based systems with the anti-tumour agent, 2,3-dihydro-1H-imidazo(1,2 b)pyrazole (IMPY, NSC (51143), a ribonucleotide reductase inhibitor. No evidence was obtained of direct complexation in aqueous media at 25 degrees C between IMPY and Fe2+ (aq) (pH 1.5-6.8) or Fe3+ (aq) (pH 1.0-3.5), nor with a mu-oxo-bridged iron dimer (Fe--O--Fe) system. There was definitive spectral evidence of complexation of IMPY with protoporphyrin IX iron (II) at pH 7.4 and 12.9 both in the absence and presence of carbon monoxide bound at the haem-iron site. Binding of IMPY to protoporphyrin IX iron (III), in contrast, was not detected. Binding between IMPY and various iron sites important in biochemistry is discussed briefly, especially in relation to the structural properties of IMPY (from X-ray data) and the Fe--O--Fe bridge system in ribonucleotide reductase and model systems. The difficulties of the use of free heterocyclic nitrogenous bases in medicinal chemistry are discussed. PMID- 3329913 TI - Both natural and induced murine anti-TNP antibodies possess anti-DNA activity. AB - Sera of BALB/c mice immunized with either trinitrophenyl (TNP) coupled to bovine serum albumin (TNP/BSA) and Freund's adjuvant or TNP/BSA and TNP coupled to mouse serum albumin (TNP/MSA) without adjuvant were tested for antibody activity against a panel of antigens: TNP/BSA, DNA, actin, myosin, tubulin and transferrin. Anti-DNA antibody activity in the serum increased significantly in immunized mice; this activity followed the increase in the anti-TNP titres. Sera from MRL/lpr/lpr autoimmune mice were also tested for antibody activity against a panel of antigens. Again, it was found that the level of the anti-TNP antibodies followed the level of anti-DNA antibodies. Purified antibodies isolated from both immunized BALB/c and MRL/lpr/lpr mice on a dinitrophenol(DNP)-lysine immunoadsorbent shared antibody activity against both TNP and DNA. The results obtained suggest that a single region in the antibody binding site is responsible for both anti-DNA and anti-TNP activities, that TNP-like groups may represent a "public epitope" carried by various antigens and that antibodies obtained after experimental immunization and antibodies appearing in autoimmunopathological situations apparently possess similar specificities. PMID- 3329912 TI - Charge transfer-oxy radical mechanism for anti-cancer agents. AB - The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6 mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants. PMID- 3329914 TI - Biochemical and immunochemical studies of the expression of glycosphingolipid based ABH and related antigens in normal cells and in plasma. PMID- 3329915 TI - Early erythroid markers as probes for normal and leukaemic erythroid differentiation. PMID- 3329916 TI - Blood-group-related antigens in colonic carcinogenesis. PMID- 3329917 TI - Sucrase-isomaltase in colon cancers: an example of re-expression of a foetal enzyme with associated blood group antigens. PMID- 3329918 TI - [Smoking and lung cancer]. PMID- 3329919 TI - Chronic respiratory disease and sleep in adults. PMID- 3329920 TI - Detecting and evaluating chemical-induced lung damage in experimental animals. PMID- 3329922 TI - The impact of technology upon medical history research: the past, the problems, the potential. AB - The stereotypical view of the historian is that of a stodgy, bespectacled individual poring over tomes of printed text, dusty manuscripts, and thousands of index cards. In the twentieth century, however, many historians have relied increasingly on technological aids to assist in research. This paper focuses on technological developments of this century that have had some impact on medical history research, beginning with the photostat early in this century. It is argued that online bibliographic databases, although relatively recent and not yet fully developed, are only the beginning of technological aids to historical research. Other computer-assisted historiographical applications are examined and the potentials of developing technologies are explored. The specific and inherent problems of using technology in historical research are also presented, as is the need for an evolving role of libraries in dealing with these problems. PMID- 3329921 TI - Organizational change in the Medical Library Association: evolution of the continuing education program. AB - "Change" is a critical dimension of contemporary experience. Library associations are not exempt, and they change in ways similar to other organizations. According to some authorities, four phases typify the process: diagnosis, design, implementation, and incorporation. Focusing on changes in the Medical Library Association's longstanding program of continuing education, the authors utilize the "phase framework" to chart that association's movement from a management system depending primarily upon volunteers to one in which professional staff figure prominently. The historical review serves a heuristic purpose for individuals and institutions in identifying characteristic features of the change process. PMID- 3329923 TI - A CATLINE SDI for the reference department: collection development and current awareness tool. AB - A method for using a CATLINE SDI (selected dissemination of information) as a current awareness and collection development tool for the health sciences reference department is described. This paper reports three years of experience with this service in an academic health sciences library. It emphasizes the exploitation of four data elements in the CATLINE file: the Abstracting and Indexing Tag (AI) Data Element; the Shelving Location (SL) Data Element; the MeSH Heading (MH) Data Element; the Subheading Qualifier (SH) Data Element. PMID- 3329924 TI - Hearing as a community health problem. PMID- 3329925 TI - Anatomical features of the auditory pathway from cochlea to cortex. PMID- 3329926 TI - The physiology of the organ of Corti. PMID- 3329927 TI - Mechanics of middle and inner ear. PMID- 3329928 TI - Physiology of the cochlear nerve and cochlear nucleus. PMID- 3329929 TI - Physiology of higher auditory system. PMID- 3329930 TI - The pathophysiology of hearing. PMID- 3329931 TI - Psychophysics of normal and impaired hearing. PMID- 3329932 TI - Speech perception in normal and impaired hearing. PMID- 3329933 TI - Electrophysiological measures of hearing function in hearing disorders. PMID- 3329934 TI - Development of surgery for conductive deafness during the past 25 years. PMID- 3329935 TI - Secretory otitis media in childhood. PMID- 3329936 TI - Hearing disorders in children. PMID- 3329937 TI - Tinnitus and its management. PMID- 3329938 TI - Auditory rehabilitation. PMID- 3329939 TI - [Yellow fever: desensitization to an anti-amaril 17 D vaccine performed on a patient with anaphylaxis to eggs]. PMID- 3329940 TI - [Isolated nocturnal hypoxemia in chronic respiratory insufficiency. Significance of its correction]. PMID- 3329941 TI - [Incidence and significance of monoclonal gammapathies in dogs. Comparison with those in humans]. PMID- 3329942 TI - [Eulogy on Alexandre Monnier (1904-1986)]. PMID- 3329944 TI - [Evaluation of the costs of emergencies]. PMID- 3329943 TI - [A theory of conception (Soranus of Ephesus)]. PMID- 3329946 TI - [100 years later...the rabies virus]. PMID- 3329945 TI - [From the detection to the prevention of cancer of the cervix uteri. A 22-year appraisal]. PMID- 3329947 TI - [Supplemental in-depth study of an epidemiological survey performed in a school environment on the occurrence of goiter and iodine deficiency in Languedoc Roussillon]. PMID- 3329949 TI - Transportation of the wounded: the models of the Armed Forces Medical Museum. PMID- 3329948 TI - EXPERFARM: a new package in BASIC for teaching genetics. AB - We have developed two interactive computer programs (together referred to as EXPERFARM), which enable simulation of a great variety of genetic situations. This package is designed for teaching basic genetics as well as quantitative and population genetics. The main advantages of EXPERFARM are its great versatility, as different situations can be simulated by simply changing the inputs, and the small amount of training necessary for the users. PMID- 3329950 TI - The medical period room. PMID- 3329951 TI - An alternative perspective: the medical period room. PMID- 3329952 TI - [The significance of a behavioral approach to bruxism: theoretical aspects and therapeutic perspectives]. PMID- 3329953 TI - [Periodontal-prosthetic relations in the anterior arch: clinical approach]. PMID- 3329954 TI - [Root anchorage and roots at "high risk"]. PMID- 3329955 TI - [Cast anatomic post for reconstruction of single-rooted teeth]. PMID- 3329957 TI - Continuous infusion or intravenous bolus: what is the rationale for doxorubicin administration? AB - In order to achieve a better therapeutic index of anticancer drugs, numerous authors are using continuous infusion therapy rather than classical intravenous bolus injection. In the case of doxorubicin or daunorubicin numerous experimental data have been published, which could provide a rationale to this clinical problem. However, due to the variety of the approaches used, the results are inconsistent and no definitive conclusion can be drawn. Several clinical phase I and II trials have been performed since 1980; they show that the toxicity of doxorubicin may be reduced by the use of continuous infusion, but the preservation of the efficacy of the drug has never been proved. Comparative phase III trials are required before this schedule of administration become routine procedure for this drug. PMID- 3329956 TI - Endometriosis and infertility: treatment is always necessary. AB - The incidence of endometriosis appears to be increasing, but is possibly due simply to the more widespread use of diagnostic laparoscopy. Whilst a clear pathogenetic role for endometriosis resulting in tubo-ovarian distortion and infertility is obvious, a causal role for mild endometriosis in infertility has not been established. Any one of several factors may result in both endometriosis and infertility. Nevertheless, endometriosis is best treated at the time of diagnosis in order to limit progression of the disease. The preferred method of treatment is medical, with surgery being reserved for those endometriotic lesions not responding to medical treatment. Conservative surgery will not eradicate microscopic foci, and it is possible that the surgery itself may result in adhesion formation. The choice of medication should be individualized, as the side-effects may not be readily tolerated by some women. Maintenance of amenorrhoea may not be essential to therapeutic efficacy, as normally sited and ectopically sited endometrial tissue may respond to hormonal manipulation in different ways. PMID- 3329958 TI - Ventriculojugular shunt against the direction of blood flow. III. Operative technique and results. AB - One hundred hydrocephalic patients were treated over a 5-year period by shunting the cerebrospinal fluid (CSF) to the internal jugular vein (IJV) against the direction of blood flow. The patients were divided into two groups according to rigidity of their craniums. The pressures recorded during the operations confirmed the results of the experiments in Part II of this investigation. Fifteen patients had their shunting catheters removed or died due to infection (14 patients) or hemorrhage inside a brain tumor (1 patient). The shunts of 12 patients were revised due to technical faults that were corrected in 9 cases. There were no failures or complications related to the dynamics of the shunt. In the 82 patients who benefitted from the shunt, the clinical improvement was dramatic. Regression of the ventriculomegaly was inversely proportional to the degree of preoperative ventricular dilatation. In 5 infants the size of the enlarged head was reduced during surgery. Valveless shunting catheters were used in the first 4 patients, and specially designed valved catheters were used in 96 patients. The follow-up period was up to 5 years. PMID- 3329959 TI - Medulloblastomas: a review of 11 cases. AB - The authors review 11 cases of medulloblastomas, 9 of which were diagnosed and treated in the last 6 years. All were uniformly treated by surgery, radiotherapy and chemotherapy, according to the SIOP protocol. Complications and results are described. PMID- 3329961 TI - Delayed foreign-body reaction to silk sutures in pediatric neurosurgical patients. AB - Nonabsorbable silk sutures have been a frequently used foreign material in neurosurgery. In general, they are reliable and safe with minimal bio incompatibility. Three pediatric neurosurgical patients came to clinical attention, however, because of delayed foreign-body reactions to silk sutures. The delayed atypical presentation of these patients delayed appropriate diagnosis and therapy. In two patients, the reaction presented as a delayed inflammation 7 years following surgical suture placement. In the other patient, the reaction caused delayed recurrent shunt failures and surgical wound breakdown. These three cases are used to introduce a discussion of the delayed response of the host to foreign material and its pertinence to neurosurgery. PMID- 3329962 TI - Sex and the renal transplant patient. PMID- 3329960 TI - Ultrasound-guided brain abscess aspiration in neonates. AB - Four cases of brain abscess in neonates are described, diagnosed by ultrasonography and CT. All abscesses were confirmed surgically. One patient was operated on 5 weeks after diagnosis because of initial parental refusal. The etiology in all cases was meningitis superimposed on an hypoxic-ischemic insult. Two cases had a single abscess while the other two had multiple lesions. All cases were operated on with intraoperative ultrasound examination through the fontanelle. The case with delayed aspiration showed complete evolution from localized cerebritis to complete capsule formation with mass effect. One abscess was sterile, and in the others grew Klebsiella pneumoniae and Enterobacter aerogenes. The microorganism initially isolated from the lumbar CSF was also found in the abscess. Even after sterilization of the lumbar CSF, all abscesses were still present. Ultrasound examination and CT are compared. PMID- 3329963 TI - Comparison trial of clindamycin with aztreonam or gentamicin in the treatment of postpartum endometritis. AB - Sixty-two patients who had postpartum endometritis were treated with clindamycin in combination with either aztreonam or the aminoglycoside gentamicin. Currently, the combination of clindamycin and an aminoglycoside constitutes a treatment of choice for this condition. Our results suggest that aztreonam can be substituted for an aminoglycoside in the treatment of postpartum endometritis with similar clinical outcomes. PMID- 3329964 TI - Cisapride in the management of chronic functional dyspepsia: a multicenter, double-blind, placebo-controlled study. AB - The effects of cisapride, a nondopaminolytic motility-enhancing agent, were studied in 56 patients with chronic functional dyspepsia; all had symptoms suggestive of delayed gastric emptying. The patients received 4 mg or 8 mg of cisapride or placebo orally three times daily for two successive three-week periods according to a randomized, double-blind, crossover study design. Although there was a high placebo response (55% showed good or excellent results), the global response to treatment was significantly (P = 0.024) in favor of cisapride (75% had good or excellent results). The drug was particularly superior to placebo (P = 0.03) in the improvement of a cluster of symptoms typical of postprandial discomfort, including early satiety and nausea. Side effects were minimal. PMID- 3329965 TI - Cefoperazone-sulbactam combination in the treatment of urinary tract infections: efficacy, safety, and effects on coagulation. AB - Seventy hospitalized patients with upper urinary tract infections were treated with cefoperazone (2 gm) and sulbactam (1 gm) every 12 hours for three or more days. All but six patients also received vitamin K. Forty of the 70 patients (57%) were cured of infection at one week after treatment, 13 relapsed, 11 had reinfections, and six were lost to follow-up. There were no treatment failures. Escherichia coli was the predominant pathogen (62% of isolates). Overall there was 15% resistance to cefoperazone and all resistant isolates were susceptible to the combination of agents. Synergy was demonstrated in 26% of isolates. One uroseptic patient who had an organism resistant to both study agents, but susceptible to the combination, was cured. Two of six patients who did not receive vitamin K demonstrated abnormal coagulation patterns and one had an associated major bleeding complication. Although 12 of 64 (19%) patients who received vitamin K had at least one coagulation abnormality, there were no significant bleeding complications in this group. PMID- 3329966 TI - Clozapine in the treatment of schizophrenic patients: an international multicenter trial. AB - One hundred twenty schizophrenic patients were treated with clozapine for two months in accordance with a standard trial protocol at ten research centers in the USSR, Czechoslovakia, Hungary, Poland, Bulgaria, and in the GDR. The daily dose ranged from 50 mg to 550 mg (mean: 272.1 mg for responders; 298 mg for nonresponders). In 94 patients (78%) the disease was clearly progressive; in 57 (47.5%) it was continuous; in 63 (52.5%) it was episodic. Before the start of clozapine treatment, 95 of the patients (79%) had been receiving other neuroleptics. There was a positive therapeutic response in 80% of the responding patients. The effect of clozapine was closely related to the dominant syndrome structure of the psychosis: a positive response was noted in 89% of patients with delusional, hallucinatory-delusional, and catatonic states and in 60% of patients with affective-delusional syndromes. Moderate side effects were noted in 87 patients (73%). The incidence of side effects reached a peak during the first four weeks of treatment and then declined despite maintenance of or even an increase in the daily clozapine dose. Hematological changes (moderate leukocytosis and thrombocytopenia) were noted in eight patients (6.7%). PMID- 3329967 TI - Symptomatic treatment of chronically recurring tension headache: a placebo controlled, multicenter investigation of Fioricet and acetaminophen with codeine. AB - A double-blind, randomized, multicenter investigation was conducted to compare the efficacy and safety of Fioricet, acetaminophen with codeine, and placebo for the symptomatic treatment of tension headache. At the onset of a typical headache, the patients took two capsules of their assigned study medication and rated responses over the next four hours in three target symptoms areas: pain, emotional or psychic tension, and muscle contractions or stiffness in the head and neck. Physicians made global assessments of the same symptom responses and of adverse reactions for each patient. One hundred ninety-eight patients were evaluated. Both active analgesic preparations were more effective than placebo in relieving pain and muscle stiffness or contractions. Fioricet, but not acetaminophen with codeine, was significantly better than placebo in alleviating emotional or psychic tension; Fioricet was also significantly better than acetaminophen with codeine in relieving this symptom. Certain analyses suggested the possibility that Fioricet had a faster and more sustained analgesic effect than acetaminophen with codeine. By the end of the four-hour trial, significantly more patients achieved complete pain relief with Fioricet than with acetaminophen with codeine. The quality and quantity of adverse reactions did not differ significantly among the treatment groups. None was serious, and all abated without medical intervention. PMID- 3329969 TI - A study of cell migration in the adrenal cortex of the rat using bromodeoxyuridine. AB - Bromodeoxyuridine (BrdU) was administered by a single intraperitoneal injection to immature (14 days) male and female and adult male Sprague-Dawley rats. Animals were killed at intervals from 2 hr to 28 days following injection. Labelled cells in the adrenal cortex were identified by an indirect immunoperoxidase technique using a monoclonal antibody to BrdU. At 2 hr, labelling was maximal in the outer zona fasciculata and zona glomerulosa in both prepubertal and adult rats. The numbers of immunopositive cells were greater in the 14 day rats. In both groups, the front of immunopositive cells moved deeper into the cortex with time. These results support the centripetal migration theory of adrenal growth. PMID- 3329970 TI - Saccharomyces cerevisiae strains sensitive to inorganic mercury. III. Tyrosine uptake. AB - In Saccharomyces cerevisiae, the HGS2-1 allele confers sensitivities to inorganis mercury (Ono and Sakamoto 1985) and to excess fermentable sugars such as glucose (Sakamoto et al. 1985); exogenous tyrosine antagonizes both inorganic mercury and excess glucose. In this study, the inorganic mercury sensitive strain has been shown to have about twice more glucose-1,6-bisphosphate and slightly less pyruvate than the normal strains, suggesting that the inorganic mercury sensitive strain has the reduced aldolase activity. It has been also shown that the growth retarded cells accumulate trehalose, by which the lower level of glucose-6 phosphate in the inorganic mercury sensitive strain is accounted for, and that inorganic mercury, presumably excess glucose also, causes growth inhibition via depletion of cellular tyrosine. The mechanism how cellular tyrosine is depleted by inorganic mercury or excess glucose is accounted for by the facts that (1) the tyrosine uptake activity is decreased with increase of glucose concentration in growth medium, (2) HGS2-1 enhances the effect of glucose on the tyrosine uptake activity, and (3) inorganic mercury inhibits the tyrosine uptake system by binding to its SH-group(s). Thus, it is concluded that the role of tyrosine is not to detoxify inorganic mercury nor excess fermentable sugars but simply to counteract depletion of cellular tyrosine induced by them. PMID- 3329968 TI - Comparison of diflunisal and piroxicam in the management of patients with rheumatoid arthritis. AB - The efficacy and tolerability of diflunisal (500 mg orally, twice daily) and piroxicam (20 mg orally, once daily) were compared in a 12-week open-label study in 44 patients with active rheumatoid arthritis. Both medications were equally effective and generally well tolerated. No significant differences were found between drug groups. Both groups showed statistically significant improvement in the overall number of swollen and tender joints, painful joint count, and the patients' assessment of pain and disease severity. Two (9%) of 23 patients in the diflunisal group and one (5%) of 21 patients in the piroxicam group reported adverse effects. Only one patient withdrew from the study because of side effects (lightheadedness during use of diflunisal). It is concluded that both diflunisal and piroxicam are highly effective and generally well tolerated in the management of rheumatoid arthritis. PMID- 3329972 TI - Mutations suppressing the effects of a deletion of the phosphoglucose isomerase gene PGI1 in Saccharomyces cerevisiae. AB - A mutant with a deletion covering the phosphoglucose isomerase gene PGI1, allele pgil delta, can only grow on a medium containing fructose and low concentrations of glucose whereas growth is completely inhibited by glucose concentrations higher than 0.4%. This was used to select suppressor mutants restoring growth on synthetic media with 2% glucose as the sole carbon source. One complementation group, SPG1, was defined by recessive mutations. The ability to grow on glucose media was strictly dependent on functional mitochondria. The generation time of the selected mutants on YEP glucose was 6-8 h. No ethanol was formed from glucose and the levels of respiration were very high. These phenotypes were also observed in single pgil delta mutants when growing on fructose media supplemented with 0.4% glucose. The other glycolytic enzymes, the enzymes of the glucose-6 phosphate oxidation pathway as well as catabolite repression were normal in suppressed pgil delta mutants. The suppressor mutation alone caused no abnormal phenotype. The results suggest that the spg1 suppressor mutations allow S. cerevisiae pgil delta mutant strains to grow on glucose by using the Pentose-P cycle in combination with unusual strong respiration. PMID- 3329971 TI - Base analogue mutagenesis in yeast and its modulation by pyrimidine deoxynucleotide pool imbalances: incorporation of bromodeoxyuridylate and iododeoxyuridylate. AB - Cells of the yeast, Saccharomyces cerevisiae, which are auxotrophic for thymidylate (tmpl) can also incorporate analogues of thymidylate. When the base analogue, 5-bromodeoxyuridylate, is incorporated into tmpl yeast cells it is lethal and mutagenic. Both lethality and mutation induction can be drastically altered by perturbation of the pyrimidine nucleotide pools. Analysis of mutation induction, bromodeoxyuridylate incorporation into DNA, and cell viability under various conditions revealed: (1) lethality and mutagenesis can be uncoupled, (2) thymidylate enhances mutagenesis and deoxycytidylate suppresses it, (3) mutation induction is not correlated with the magnitude of bromodeoxyuridylate incorporation into DNA. Therefore, in yeast, the pyrimidine nucleotide pools have a powerful effect on bromodeoxyuridylate mutagenesis. Both bromodeoxyuridylate and iododeoxyuridylate are extensively incorporated into the DNA of tmpl yeast cells; however, iododeoxyuridylate is non-mutagenic. Replication proceeds at the same rate in the presence of the natural substrate or either analogue. When cells are supplied with thymidylate and bromodeoxyuridylate together, there is no discrimination against bromodeoxyuridylate as a DNA precursor. However, in the presence of thymidylate and iododeoxyuridylate, there is a 3 to 1 discrimination against iododeoxyuridylate as compared to thymidylate. PMID- 3329975 TI - Genetic nomenclature and gene list of the fission yeast Schizosaccharomyces pombe. AB - The nomenclature rules for the genetics of the fission yeast Schizosaccharomyces pombe have been fixed for the first time, after discussion among scientists working with this organism. Conventions are proposed for the naming of genes and alleles that are obtained by classical means or by reverse genetics. In addition a list has been compiled of 460 known genes of S. pombe. It includes genes defined both by classical mutation analysis and by molecular cloning. 270 genes have been assigned either to one of the three nuclear chromosomes or the mitochondrial genome. PMID- 3329973 TI - Genetic mapping of two pairs of linked ribosomal protein genes in Saccharomyces cerevisiae. AB - We have used the 2 mu mapping method described by Falco and Botstein (1983) and tetrad analysis to map four ribosomal protein genes (two linked pairs) in S. cerevisiae. One pair (rp28-rp55 copy 1) is on chromosome XV, 14 cM proximal to ARG8. The other pair (rp55-rp28 copy 2) is 19 cM from the centromere on the left arm of chromosome XIV. To map copy 1 we used the E. coli beta-galactosidase gene rather than a yeast gene to mark the ribosomal protein chromosomal locus. This provided a more sensitive color screening assay for chromosome loss in the 2 mu method. It also removed the restriction that the mapping tester strains must be mutant for the plasmid marker. PMID- 3329974 TI - Microheterogeneity in Aspergillus nidulans 5S rRNA genes. AB - We have determined the sequence of 4 Aspergillus nidulans 5S rRNA genes and compared it with 4 previously established sequences. No extensive homologies are found in 5' flanking sequences, but in the 3' flanks of two genes and two pseudogenes similar sequences are observed. In the coding sequences differences occur in 7 positions. Two 5S rRNA genes which are found in one plasmid 1.1 kb apart are located in opposite orientations. PMID- 3329977 TI - [Bacteriologic diagnosis of pneumococcal pneumonia: a report of 50 cases]. PMID- 3329976 TI - [Primary rhabdomyosarcoma of the lower respiratory tract (report of 2 cases and review of literature)]. PMID- 3329978 TI - [Tween 80 egg medium for isolation of mycobacteria]. PMID- 3329979 TI - [Use of fiberoptic bronchoscopy in respiratory emergencies]. PMID- 3329980 TI - [Pulmonary cryptococcal granuloma: report of 2 cases and review of literature]. PMID- 3329982 TI - [Gastroesophageal reflux and lung diseases]. PMID- 3329981 TI - [Idiopathic pulmonary hemosiderosis]. PMID- 3329983 TI - [Hypoxic pulmonary vasoconstriction]. PMID- 3329984 TI - [Nursing of patients with pancreatectomy and autoplastic transplantation]. PMID- 3329985 TI - [Bactericidal activity of disinfectants against certain bacterial strains. Klebsiella pneumonia]. AB - Twenty disinfectants were tested against a strain of K. pneumoniae. A suspension test with incremental addition of microorganisms was used. The influence of interfering substances (proteins and hard water) on the activity of disinfectants was also determined. Iodine compounds were influenced by proteins in distilled and hard water. The presence of mineral ions inactivated the polyvinylpyrrolidone iodine 10% and chloroxylenol preparations against K. pneumoniae. The activity of some iodine products disappeared at the second and third incremental addition of microorganisms; the chloroxylenol and the phenolic compounds were inactivated by proteins at the third incremental addition. The sensibility of K. pneumoniae to the other disinfectants was not influenced by proteins, ions and incremental bacterial additions. PMID- 3329986 TI - [2 new cases of rhinoentomophthoromycosis diagnosed in the Central African Republic (review of the literature)]. AB - After a historical account and review of the published literature on rhinoentomophthoromycosis, we report two recently recognized cases in Central African Republic. The first case was a 32 year-old "peuhl" woman with typical facial deformation that gave her a "hippopotamus-woman" aspect. The second case was a 53 year-old man with lesions that were less typical and limited to one half of the face only. In both cases, hypodermic nodules were palpable and it is likely that inoculation occurred by scratching of a skin lesion. The woman originates from a savanna region whereas the second patient is from a forest area. In both cases, culture were positive for Conidiobolus coronatus. Treatment with itraconazole was instituted for both patients. PMID- 3329987 TI - [Hepatic amebiasis at Niamey Hospital (Nigeria)]. AB - The authors report the results of a prospective study on hepatic amebiasis realized in national hospital of Niamey (Republic of Niger). Hepatic amebiasis is uncommon in Niger as in other hot and dry countries of Africa whereas it is common in hot and damp areas of the continent. These results point out the hypothesis of a hepatotropic strain of Entamoeba histolytica uncommon in Sahelia area whereas the amebiasis infestation is frequent. PMID- 3329989 TI - [Malaria situation in China. 1986. Malaria Commission, Committee of Medical Sciences]. PMID- 3329988 TI - [Effectiveness of mass chemotherapy campaigns with diethylcarbamazine on blood microfilaria of Wuchereria bancrofti in Mayotte]. AB - An evaluation of the microfilarial index has been carried out in a randomised population, during April and May 1986, to determine the efficacy of long course mass chemotherapy. A single dose of DEC at 6 mg/kg was distributed to the whole population of the island, every 4 months, in 1985 and 1986. The survey was done three months after the treatment. 1,307 thick blood films have been collected in night-time. The prevalence of microfilaremia was 1.9% as compared with 17.1% in 1981 in the conditions. The control measures were considered as quite satisfactory, and it was decided to continue mass chemotherapy together with vector control. PMID- 3329990 TI - [Identification of protective activity of monoclonal antibodies against Plasmodium falciparum]. PMID- 3329991 TI - [A study of monoclonal antibody ELISA test to detect malaria parasite antigens]. PMID- 3329992 TI - [Scanning electron microscopic study on the late stage of sporogony of Plasmodium vivax]. PMID- 3329993 TI - [Therapeutic effects of 13 combinations of antimalarials against Plasmodium berghei "NS" strain]. PMID- 3329994 TI - [Studies on the reappearance of gametocytes of Plasmodium berghei]. PMID- 3329995 TI - [Transplantation of a 3d molar into an autologous iliac crest graft in the mandible. A case report]. PMID- 3329996 TI - [Mandibular reconstruction with a new titanium framework, autogenous cancellous bone and hydroxylapatite. Initial results]. PMID- 3329997 TI - [Ultrasonic imaging of the head and neck region]. PMID- 3329998 TI - [A new dimension in the microscopic analysis of bone structures--scanning acoustic microscopy (SAM). Preliminary report]. PMID- 3329999 TI - [Initial report on surface and deep structure studies of human bone tissue using reflection-scan-acoustic microscopy (R-SAM). A comparison between light and ultrasonic microscopy imaging]. PMID- 3330000 TI - [Long-term results with a peri-mandibular sling for stabilization of lower complete dentures]. PMID- 3330002 TI - [On the "Notes on Nursing" by Florence Nightingale. 10]. PMID- 3330001 TI - [Conventional grafting technics and endosseous implants. A treatment concept in rehabilitation following radical tumor surgery of the lower oral cavity]. PMID- 3330003 TI - [Witches, midwives, and nurses. A history of women healers (1)]. PMID- 3330004 TI - [Clinical study of embryonic bone implantation]. PMID- 3330005 TI - [A short-term clinical evaluation of etched casting of resin-bonded bridges fabricated with Co-Cr alloy]. PMID- 3330006 TI - [Analysis of bacterial cultures from 40 cases of periodontal abscess and their drug sensitivity]. PMID- 3330008 TI - Relationship of tumour necrosis factor and endotoxin to macrophage cytotoxicity, haemorrhagic necrosis and lethal shock. AB - In this communication we discuss preliminary evidence suggesting a very strong synergism between tumour necrosis factor (TNF) and lipopolysaccharide (LPS) or between TNF and other bacteria in causing haemorrhagic necrosis and lethal shock. We found that TNF by itself does not cause haemorrhagic necrosis when injected into normal skin. TNF also had a rather low systemic toxicity when injected into disease-free, germfree-derived, defined-flora animals. On the other hand the addition of small amounts of LPS markedly raised the lethality of intravenous TNF treatments, and LPS injected into normal skin 'prepared' the site of injection for subsequent induction of haemorrhagic necrosis by locally injected TNF. Similar synergism was observed between TNF and mycoplasma. We suggest that the synergism between TNF and bacterial endotoxin (or other bacteria or bacterial products) may be part of an important defence mechanism against infections which is independent of specific immunity mediated by B and T cells. This synergism may be useful in increasing the therapeutic effects of TNF on tumours if the development of systemic toxicity in this treatment can be prevented. PMID- 3330007 TI - [Ultrasonic tomography and radionuclide imaging of parotid neoplasms]. PMID- 3330010 TI - Lymphotoxin and tumour necrosis factor as possible mediators of an inflammatory response. PMID- 3330009 TI - Effects of tumour necrosis factor and related cytokines on vascular endothelial cells. AB - Tumour necrosis factor (TNF) and related cytokines have been found to alter the phenotype of vascular endothelial cells so as to promote coagulation, inflammation and immunity. We have used recombinant human TNF, lymphotoxin (LT), interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta) to study and compare the effects of these molecules on cultured human endothelial cells (HEC). All four mediators cause HEC monolayers to reorganize from an epithelioid to a fibroblastoid morphology. Reorganization is slow (days), reversible upon cytokine withdrawal and enhanced by co-addition of immune interferon. Coincident with morphological change, TNF and LT (but not IL-1 alpha or IL-1 beta) cause a marked increase in HLA-A, B mRNA and antigen expression. TNF and LT also induce a slow increase in the mRNA levels and cell-surface expression of IL-1 species. All four cytokines have been reported to enhance HEC adhesiveness for lymphocytes and inflammatory leucocytes; these changes temporally coincide with a rapid (hours) and sustained increase in expression of intercellular adhesion molecule 1 (ICAM 1), and with a rapid but transient de novo expression of an endothelial-leucocyte adhesion molecule (detected by antibody H4/18), respectively. TNF and LT induce reciprocal tachyphylaxis for the reinduction of H4/18 binding but do not inhibit induction by IL-1 alpha and IL-1 beta; similarly, IL-1 alpha and IL-1 beta induce reciprocal tachyphylaxis but do not inhibit TNF or LT. We have used the binding of H4/18 to explore the mechanism of action of TNF. Tumour-promoting phorbol esters, but not agents which increase cytoplasmic calcium concentrations, were found to induce binding, suggesting a possible involvement of the protein kinase C pathway in the response of HEC to TNF. Cells pretreated for 24 hours with phorbol esters cannot be reinduced to express H4/18 binding by phorbol esters yet retain full responsiveness to TNF. Thus TNF also appears to act on HEC through a pathway independent of protein kinase C activation. Collectively, these effects of TNF and related cytokines may be understood as examples of endothelial cell activation. PMID- 3330011 TI - Clinical studies with tumour necrosis factor. AB - The mechanism of tumour necrosis factor (TNF) cytotoxicity remains unknown. The in vivo antitumour effects of TNF may be related to direct cytotoxicity, immunomodulatory effects or endothelial effects on tumour vasculature. Phase I and early Phase II clinical trials of human recombinant TNF are under way in Japan, the USA, the UK and Germany. The maximum Phase II dose for TNF has not been established. The clinical toxicity of TNF is generally similar to that of other biological agents. Systemic toxicity, including fever, chills, anorexia and nausea, has been seen in most patients treated with TNF and has not been clearly related to dose. Other toxicities have included liver function abnormalities, hypotension, transient neurological changes and haematological abnormalities. Few clinical responses have been reported but organized Phase II testing remains to be completed. Combination trials with interferons have recently been initiated. Phase II efficacy studies of TNF as a single agent and in combination are needed for an assessment of the value of this agent in cancer therapy. PMID- 3330012 TI - Possible relationships between in vivo antitumour activity and toxicity of tumour necrosis factor-alpha. AB - The discoveries of a tumour necrosis-inducing substance in sera of experimental mice and of cytotoxic factor(s) in cultures of stimulated lymphoid cells triggered intense research efforts which have culminated in the production of two distinct but related recombinant materials, human tumour necrosis factors TNF alpha (cachectin) and TNF-beta (lymphotoxin). The necrosis of tumours by TNF is but one feature of high doses of these immune system hormones that possess numerous biological activities. Apart from their direct cytotoxic/cytostatic activities against tumours in vitro and in vivo, the in vivo antitumour activities of TNF-alpha or TNF-beta may involve the following biological activities: the induction of interleukin 1 production; activation of polymorphonuclear neutrophil functions; modulation of endothelial cell functions; and augmentation of specific immune functions. Many of these activities are associated with an irreversible acute inflammation which appears to be the immediate lethal effect of TNF on transplantable tumours in mice. This inflammation leads to thrombosis, disruption of the tumour's blood supply and, finally, tumour death. Inflammatory effects of high doses of TNF are also seen in the rodent gastrointestinal tract but here the inflammation seems to be reversible. PMID- 3330013 TI - Cytocidal activity of tumour necrosis factor: protection by protease inhibitors. AB - The mechanism of the cytostatic and cytocidal activities of TNF was studied in human tumour cells. BT-20 breast and ME-180 cervical cancer cells were significantly growth-inhibited by TNF, but other cells were not. When protein synthesis was inhibited by cycloheximide, however, TNF was cytotoxic for all cells except BT-20 cells. This suggests that different mechanisms are responsible for the cytostatic and cytocidal activities of TNF. The sensitivity of different cell lines could not be correlated with the number or affinity of TNF receptors. Some protease inhibitors completely protected human and murine cells from TNF cytotoxicity. Inhibitors of chymotrypsin-like proteases were more effective than inhibitors of trypsin-like proteases. Reversible and irreversible inhibitors (such as alkylating compounds) were both protective. The cells were best protected when pretreated with inhibitors before the addition of TNF. When the protease inhibitors were removed the cells gradually lost their resistance to TNF cytotoxicity. The inhibitors did not interfere with the functioning of TNF receptor complexes, since SK-MEL-109 melanoma cells treated with a protease inhibitor synthesized TNF-induced proteins. These findings suggest that a protease is involved in the cytocidal activity of TNF. PMID- 3330014 TI - [Advances in the radiotherapy of myasthenia gravis]. PMID- 3330015 TI - [Intracerebral transplantation of the adrenal medulla in the treatment of parkinsonism]. PMID- 3330016 TI - [Small vessel anastomosis with lasers]. PMID- 3330017 TI - The implementation of pit and fissure sealants. Lessons in information transfer about preventive dentistry. PMID- 3330018 TI - [The blink reflex]. PMID- 3330019 TI - [Legionella infection during southern travel--an underdiagnosed problem?]. PMID- 3330020 TI - [Ultrasonic evaluation of suspected small-for-gestational-age fetuses]. PMID- 3330021 TI - [Placental hemangioma--a cause of neonatal hypovolemia]. PMID- 3330022 TI - Correlation of regional insulin and glucagon content in canine pancreas and a possible interaction of A and B cells. AB - Canine pancreases divided into 8 anatomical subportions were examined for their regional insulin and glucagon content. Insulin content in the pancreas was gradually increased in the left lobe to about twice as much as that in the uncinatus, while glucagon content was increased steeply in the left lobe to 16 times as much as that of the uncinatus. Although hormonal content differs according to the anatomical area, a statistically significant positive correlation of mean regional insulin and glucagon content was observed (r = 0.994, p less than 0.001). A constant ratio of these two hormones suggests the functional coupling of A and B cells within the islets or in a given pancreatic subportion. PMID- 3330023 TI - Expression of renin and angiotensinogen genes in the human placental tissues. AB - The expression of renin and angiotensinogen genes in the human placenta and related tissues has been examined by RNA blot hybridization analysis with specific human complementary DNA (cDNA) probes. Renin mRNA was detectable in the chorion throughout pregnancy and in the hydatidiform moles, but not in the decidua, amnion or myometrium. The relative concentration of renin mRNA in the chorion was at the highest level in early pregnancy and decreased thereafter, while the total amount contained in the whole placenta was at the lowest level in early pregnancy, and increased thereafter, reaching at term about one-sixth of the total renin mRNA in the kidney. Hydatidiform moles had an even higher concentration of renin mRNA than the early chorion. There was no significant difference in either the relative concentration or the total renin mRNA content in the placentae from 4 normal and 4 toxemic pregnancies. Angiotensinogen mRNA was undetectable in any of the placental tissues, hydatidiform moles or myometrium. These results show that renin is synthesized in the placenta, possibly to play some physiological role locally by utilizing angiotensinogen which is abundantly present in the maternal systemic circulation. PMID- 3330024 TI - Self-priming effect of LH-RH on pituitary gonadotropins in hyperprolactinemic women. AB - To investigate how various concentrations of serum prolactin (PRL) influence the priming effect of luteinizing hormone releasing hormone (LH-RH) on the pituitary gland, 24 women with various blood PRL concentrations received intravenous injections of 100 micrograms of synthetic LH-RH twice at an interval of 60 minutes and their serum LH and follicle-stimulating hormone (FSH) were measured and analysed. In the follicular phase with a normal PRL concentration (PRL less than 20 ng/ml, n = 6), marked first peaks of the two hormones following the first LH-RH stimulation and enhanced second peaks after the second LH-RH administration were observed, indicating a typical priming effect of LH-RH on gonadotropins, though the second response of FSH was more moderate than that of LH. In hyperprolactinemia, in which the serum PRL concentration was higher than 70 ng/ml (n = 13), the basal concentration of gonadotropins was not significantly changed but the priming effect of LH-RH on LH and FSH was significantly decreased (p less than 0.01). No marked second peaks of LH and FSH were observed, suggesting an inhibitory effect of hyperprolactinemia on the second release of LH and FSH. In contrast, this effect was restored in a group of women whose serum PRL concentration was between 30 and 50 ng/ml (n = 5). Furthermore, enhanced second peaks of both LH and FSH were noted after successful bromocriptine therapy reduced hyperprolactinemia (PRL greater than 70 ng/ml) to less than 25 ng/ml (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3330025 TI - Changes in plasma glucose, insulin (IRI), glucagon (IRG) and free fatty acids (FFA) following alanine loading in hyperthyroid patients. AB - The responses of plasma glucose, insulin (IRI), glucagon (IRG) and free fatty acids (FFA) following alanine loading (0.1 g/kg) were observed in 9 control subjects and 7 hyperthyroid patients, before and after restoration of thyroid function to normal. Despite the persistence of impaired glucose response to alanine, the blunted IRI and IRG responses in the hyperthyroid state were improved with a significant reduction in fasting IRI and IRG after treatment. Markedly increased FFA following alanine loading in hyperthyroid patients was reduced after treatment, but the FFA concentration remained greater than in the control subjects. We tentatively conclude that the impaired alpha and beta-cell responses to alanine were temporarily induced by the direct and/or indirect effects of thyroid hormone excess. PMID- 3330026 TI - [Effect of various hormones regulating carbohydrate metabolism on the activity of cyclic nucleotide-independent kinases isolated from the human placenta]. PMID- 3330027 TI - Effects of nifedipine on coronary perfusion; recent assessment by parametric digital subtraction. AB - The effects of nifedipine on myocardial perfusion abnormalities were investigated in 6 patients with left coronary artery disease using a digital angiographic method. Selective left coronary angiograms were digitized on-line into a 256 x 256 pixel matrix, approximately 20 ECG-gated end-diastolic frames being acquired during each coronary injection. After background subtraction, parametric analysis was undertaken, measuring sequential changes in contrast opacification against time. Isochrone maps were derived showing the distribution of times to attainment of peak contrast density throughout the left ventricle (the Tmax image) reflecting myocardial perfusion, and of times to arrival of half peak opacification (the T1/2max image) as an index of coronary flow. At basal heart rate (fixed by pacing) mean Tmax was attained in well supplied myocardium at the 7th cardiac cycle, and at the 9th cardiac cycle in the least perfused territory. Overdrive pacing reduced arrival times by 2-3 cycles, but inhomogeneity persisted. After sublingual nifedipine, contrast arrival was significantly accelerated by a mean of two cardiac cycles in poorly perfused regions, and by one cardiac cycle elsewhere. After nifedipine, overdrive pacing shortened Tmax and T1/2max most markedly in the least supplied territory. Results with this new technique indicate that nifedipine has beneficial effects on regional malperfusion in coronary disease. PMID- 3330029 TI - Tissue protection by nifedipine and its calcium antagonistic derivatives in vascular damage. AB - Calcium ions are ubiquitous messengers of numerous cellular functions. Under normal conditions, they translate the membrane signal into specific cellular activity by electromechanical or electrosecretory coupling. An enhancement of the transmembrane calcium influx results in exaggerated cellular function, such as increased vascular contractility. Therefore, a reduction of transmembrane calcium influx by calcium antagonists effectively reduces high blood pressure (BP). It has been shown that the long-term treatment of genetically hypertensive rats with dihydropyridine calcium antagonists ameliorates the tissue damage that occurs in association with high BP in various organs. This tissue protection is not secondary to the reduction of hypertension as it can be demonstrated in the absence of BP reduction. This favourable effect may be attributed to the prevention of intracellular calcium overload which results in an exhaustion of energy-rich phosphates, excessive activation of proteolytic and phospholytic enzymes, membrane destruction and cellular death. In acute ischaemia experiments, inhibition of excessive transmembrane calcium influx by the dihydropyridine calcium antagonists prevents vascular and parenchymal damage. Moreover, long-term treatment with dihydropyridine calcium antagonists prevents vascular and parenchymatous damage in advanced or accelerated hypertension. In accordance with this concept, calcium antagonists have been shown to exert protective effects against acute ischaemic damage in both the heart and the kidney. PMID- 3330028 TI - Is nifedipine a suitable first-line treatment for essential hypertension in general practice? AB - Nifedipine has been used in hypertension, mainly as a third-line drug for rapid blood pressure reduction, for over 10 years. More recently it has been shown to be effective and safe in reducing mild to moderate blood pressure when used alone in a slow release formulation. A placebo-controlled study investigating the efficacy and safety of nifedipine in comparison with cyclopenthiazide-potassium has now been carried out by 4 general practitioners in the Glasgow area. Ninety four patients were entered into the study. After a 4-week placebo run-in phase, patients were randomly allocated to receive either slow-release nifedipine 20 mg b.d., or cyclopenthiazide 0.25 mg with 8.1 mmol potassium daily. The dose was doubled at week 8 for non-responders, and at week 12 the alternative drug was added if there was still no response. The patients were studied for up to 28 weeks. Nifedipine was found to have similar blood pressure lowering efficacy to cyclopenthiazide-potassium, but withdrawals from nifedipine due to side-effects at an early stage were more common. PMID- 3330030 TI - Calcium antagonist induced vasodilation in peripheral, coronary and cerebral vasculature as important factors in the treatment of elderly hypertensives. AB - Increased arteriolar tone is the pathophysiological hallmark of essential hypertension and is determined by the intracellular free calcium concentration in the vascular smooth muscle cell. Calcium influx is an important determinant of vasoconstriction and excess calcium influx-dependent vasoconstriction has been shown by plethysmographical studies in patients with essential hypertension. Calcium antagonists acutely lower BP by reducing calcium influx, calcium concentration and peripheral resistance. The degree of the attendant sympathetic nerve reflex activation and counter-regulatory mechanisms determines the antihypertensive response of the individual. Chronic monotherapy with a calcium antagonist results in an antihypertensive response, which is directly related to the patient's age and pretreatment BP and indirectly related to plasma renin levels. The resulting reduction in after-load neither leads to reduced cerebral blood flow in hypertensive patients, nor aggravates congestive heart failure. Calcium antagonists are a useful alternative to diuretics, primarily in older patients with low renin levels, either alone or combined with any other antihypertensive drug, and provide effective and safe control of blood pressure. PMID- 3330031 TI - Nitrendipine as an antihypertensive agent. AB - A double-blind, stratified and randomized multicentre trial was carried out to compare the antihypertensive efficacy of nitrendipine with that of propranolol. The dose of nitrendipine was 5-20 mg b.d., and of propranolol, 40-120 mg b.d. With nitrendipine (N = 137), systolic blood pressure (SBP) and diastolic blood pressure (DBP) fell from 156 +/- 1 to 140 +/- 1 mmHg and from 101 +/- 0 to 89 +/- 1 mmHg respectively (mean +/- SEM) (P less than 0.0001). On propranolol (N = 138), SBP fell from 156 +/- 1 to 144 +/- 2 mmHg and DBP decreased from 101 +/- 0 to 91 +/- 1 mmHg (P less than 0.0001). In a subgroup of 11 patients on nitrendipine, mean 24-hour SBP dropped from 137 +/- 4 to 128 +/- 4 mmHg and DBP fell from 92 +/- 2 to 87 +/- 2 mmHg (P less than 0.01). On propranolol, mean 24 hour SBP and DBP were decreased from 142 +/- 4 to 128 = 4 mmHG (P less than 0.05) and from 89 +/- 2 to 84 +/- 2 mmHg (P less than 0.09), respectively. Plasma renin activity was not altered significantly by nitrendipine (N = 89), but was significantly reduced from 1.86 +/- 0.24 to 1.37 +/- 0.75 ng ml-1 h-1 by propranolol (N = 88, P less than 0.002). Plasma renin activity was inversely correlated with age, but was not related to the reduction of SBP or DBP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3330032 TI - Do calcium antagonists affect platelets? AB - Inappropriate platelet activation is thought to have a pathophysiological role in several cardiovascular disorders, including ischaemic heart disease and hypertension. Calcium antagonists are increasingly used in the therapy of these diseases. An inhibitory effect on platelet activation would clearly be a useful component of their therapeutic effect. Since a raised intracellular calcium concentration is crucial for platelet activation, and much of the calcium enters from the extracellular medium, such an effect might be anticipated. In fact, calcium antagonists consistently inhibit platelet activation in vitro, and somewhat less consistently ex vivo. However, many unanswered questions remain. Clinically attained drug concentrations in plasma may be too low to be effective, there appear to be no calcium antagonist receptors on the platelet, and the mechanism of action of the drugs is unclear. More importantly, it is not known whether an anti-platelet effect, if it occurs, is of practical rather than theoretical, value to the patient. These problems will need much more investigation. PMID- 3330033 TI - Potential future developments in the field of antihypertensive drugs. AB - Since an understanding of the pathogenesis of essential hypertension is unlikely to be imminent, there is little chance that antihypertensive therapy will become curative in the near future. What progress can be expected in symptomatic therapy? In the past, nearly all major mechanisms involved in the regulation of blood pressure have become targets of antihypertensive drugs; they include the sympathetic neuro-effector system, neuronal substrates of central cardiovascular regulation, the kidney, the renin angiotensin aldosterone system and the vascular smooth muscle cell. Among drugs that influence the function of the sympathetic nervous system, the clinical potential of one mechanism of action has not yet been explored: it is the inhibition of noradrenaline release through stimulation of inhibitory receptors located at the adrenergic nerve terminals of the cardiovascular system (inhibitory presynaptic receptors). Among the multiple presynaptic receptors, dopamine receptors appear to be a particularly interesting target. The not entirely expected activity of angiotensin converting enzyme (ACE) inhibitors in essential hypertension prompted the search for renin inhibitors. Whether interruption of the cascade of the renin angiotensin system at the first reaction step by renin inhibitors, as compared to the interference at the second step by ACE inhibitors, will yield relevant progress in antihypertensive drug therapy remains to be seen. PMID- 3330034 TI - Measurement of insulin in human sera using a new RIA kit. 1. Insulin determination in the absence of insulin antibodies--conventional assay and micro modification. AB - A sensitive and versatile radioimmunoassay (RIA) for insulin was established using human insulin standard, a specific guinea pig anti-insulin antiserum and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine T method. Tracer preparations were used for as long as 6 weeks after iodination. The standard curve ranges from 0.044 to 1.2 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6 9% in the optimal range between 0.4 and 0.9 nmol/l. The average recovery of human insulin added to plasma or serum samples was 100.2 +/- 2.0% (n = 38) and 100.1 +/ 1.9% (n = 42), respectively. In addition to human insulin, porcine, canine, rabbit and bovine insulin can also be determined but not rat or mouse insulin. The cross-reactivity of the antiserum with porcine proinsulin was found to be 40% on the molar basis. The range of mean fasting plasma insulin concentrations in healthy subjects and under various pathological conditions were estimated. PMID- 3330035 TI - Measurement of insulin in human sera using a new RIA kit. 2. Determination of free and total insulin--correlations to insulin antibody levels. AB - Using the micro-scale modification of a newly developed RIA kit for insulin, we established methods for the determination of free and total insulin in serum of insulin-treated diabetics. Precipitation with polyethylene glycol 6000 or acid alcohol extraction of sera was carried out to remove or to dissociate antibody bound insulin. Both assays permit precise and accurate measurement of either serum insulin fraction. In 50 diabetic sera with tracer insulin binding of 0-97%, free (after equilibration of the sera at 37 degrees C) and total insulin levels as well as insulin antibody binding parameters were determined. There was a good correlation of free to total insulin levels with maximally 10-fold higher values of total insulin. Both free and total insulin were found to be correlated with the ability of the serum to bind insulin. In detail, binding affinities (i.e. the reciprocal of equilibrium dissociation constants) and binding site concentrations were evaluated which were shown to be positively correlated with free and total insulin levels as well. From these data we conclude that insulin antibodies in the serum may accumulate therapeutic insulin and function as a depot for delivering insulin in insulinopenic episodes (Keilacker et al., 1982 and 1986). PMID- 3330037 TI - Maintenance of pancreatic endocrine cells of neonatal rats: effect of 2 deoxyglucose on insulin biosynthesis. AB - The relationship between insulin biosynthesis and proinsulin mRNA activity was examined in pancreatic monolayer cultures of the neonatal rat. Monolayer cultures were maintained in TCM 199 medium containing 16.7 mM of either glucose or 2 deoxyglucose or in a basal medium not containing glucose for 24 hr. The fractions containing mRNA extracted from these cultures were translated in a cell-free protein synthesizing system of rabbit reticulocyte lysate. The proinsulin mRNA activity was determined by the radioactivity of the translation product immunoprecipitated using anti-insulin serum, and identified as preproinsulin with a molecular weight of 11,500 on gel electrophoresis. The amount of insulin biosynthesis was determined by the incorporation of [3H]-leucine into (pro)insulin. In islet B cells cultured in a medium with 16.7 mM glucose, insulin biosynthesis induced by 16.7 mM glucose was enhanced by 158% when cultured in basal medium without glucose. This increment corresponded nicely with a 185% increase in the proinsulin mRNA activity. However, the addition of 16.7 mM 2 deoxyglucose to the basal medium resulted in a 293% increase in glucose-induced insulin biosynthesis despite a 16% drop in the proinsulin mRNA activity, and primed a dose-dependent increase of insulin biosynthesis over the concentration range of 0 to 16.7 mM glucose. These results suggest first that in neonatal B cells insulin biosynthesis may be regulated at the transcriptional level, and second, that 2-deoxyglucose may cause the transition of the neonatal B cell to an adult-type response. PMID- 3330036 TI - Pharmacokinetics and biological activity of the new intermediate-acting insulin L SNC). AB - To assess pharmacokinetics and biological activity of the new L-SNC insulin (Berlin-Chemie, a low immunogenic pork insulin in neutral solution purified by chromatography) ten healthy male subjects were connected to the BIOSTATOR. After an overnight fast 0.4 U of L-SNC insulin per kg body weight were injected subcutaneously in the thigh of each individual. Plasma insulin concentrations rose gradually reaching their maximum values after 8 hours. According to C peptide levels there was some inhibition of endogenous insulin secretion. For the evaluation of insulin action we used the closed loop system (BIOSTATOR) which was transformed in its function into a glucose controlled dextrose infusion system. The amount of glucose delivered by the BIOSTATOR in order to maintain blood glucose steady state concentrations at the "basal" level was taken as a measure of biological activity of the injected insulin. The glucose infusion rate increased after insulin administration, reaching statistical significance after 3 hr. The maximum effect of L-SNC insulin was observed between 5 and 12 hours after injection. The overall duration of action of more than 16 hours meets the increasing need for insulin in the early morning in many diabetic patients. Therefore, L-SNC insulin should be recommended for intensified conventional insulin therapy to cover the night and to prevent dawn phenomenon in insulin dependent diabetics. PMID- 3330039 TI - Changes of expression of peritoneal macrophages Fc and C3 receptors induced by transplantable melanomas. AB - Expression of Fc and C3 receptors was studied in the rosette tests on isolated peritoneal macrophages of control and melanoma-bearing hamsters. In hamsters with transplanted melanomas an increase of the percentage of macrophages with Fc and C3 receptor expression was observed. The increase was prominent among macrophages from animals with transplanted amelanotic melanoma, a tumor line with greater malignancy and changed antigenicity and immunogenicity. PMID- 3330038 TI - Prof. Jan Slotwinski M. D. (1903-1986). PMID- 3330040 TI - [Molecular biology of insulin receptors]. PMID- 3330041 TI - Early retirement: how one dentist left practice for paradise. PMID- 3330042 TI - "Variety is the spice of life". PMID- 3330043 TI - Antiques provide unique decor. PMID- 3330044 TI - The world through a camera. PMID- 3330045 TI - The dentist and the photograph. PMID- 3330046 TI - Hydrofluoric acid. PMID- 3330047 TI - Modelling resin for casting patterns. PMID- 3330048 TI - Use of sodium nitroprusside in resistant congestive cardiac failure. PMID- 3330050 TI - Systemic lupus erythematosus with generalised bullous eruptions. PMID- 3330049 TI - Captopril in hypertension a multicentric study. PMID- 3330051 TI - Antimalarial activity of 4,4'-bis-dimethylaminodiphenyl sulfone. PMID- 3330052 TI - Genetic properties of some R plasmids of enteric bacteria. PMID- 3330054 TI - Diabetic metabolic control: how important? An appraisal. PMID- 3330055 TI - Prospects of beta-thalassemia major. PMID- 3330053 TI - Ocular malignant lymphoma. A clinical pathological study. PMID- 3330056 TI - Renal replacement therapy in children. PMID- 3330057 TI - Renal transplantation in children. PMID- 3330058 TI - Endemic vesical stone: nutritional factors. PMID- 3330060 TI - [The etched bridge in the conservative treatment of tooth abrasion]. PMID- 3330059 TI - Third generation cephalosporins. PMID- 3330062 TI - [Calcium antagonists in acute myocardial infarct? Long-term nifedipine infusion in pre-infarct angina and acute myocardial infarct]. PMID- 3330061 TI - [Treatment of inter-radicular lesions of multi-rooted teeth]. PMID- 3330063 TI - [Pulmonary edema]. PMID- 3330065 TI - [Enzymatic procedures for determining creatinine]. PMID- 3330064 TI - [Drug-induced vital disorders]. PMID- 3330066 TI - [A 25-year-old male with multiple pulmonary coin lesions]. PMID- 3330067 TI - [Lipid pneumonia as differential diagnosis of bronchial cancer]. PMID- 3330068 TI - [Acute heart arrhythmias]. PMID- 3330069 TI - [The hypertensive crisis]. PMID- 3330070 TI - [Unstable angina pectoris]. PMID- 3330071 TI - In vitro assay of packaging protein gp3 of Salmonella phage P22. AB - The packaging proteins, gp2 and gp3, of Salmonella phage P22 were separated by DEAE-sephacel column chromatography. The activity of both proteins was measured by complementation in an in vitro phage packaging assay. For the first time gp3 activity was demonstrated in vitro. The majority of the gp3 activity could be separated from gp2. While gp2 was stable during chromatography and storage, gp3 was very unstable. However, it was stable when stored as a crude extract. The ratio and interaction of these two proteins critical for phage maturation are still uncertain. PMID- 3330072 TI - [Italian standardization and classification of Neuropsychological tests. The Italian Group on the Neuropsychological Study of Aging]. PMID- 3330073 TI - [Criteria factors in the choice of designs for removable denture construction]. PMID- 3330074 TI - [Gingival pemphigus vulgaris]. PMID- 3330076 TI - [An improved technic of retainer transfer to the working cast]. PMID- 3330075 TI - [Root canal filling materials. The effect on the periapical tissues]. PMID- 3330077 TI - [Current concepts of precancerous lesions and conditions of the oral mucosa: recent trends in research]. PMID- 3330078 TI - [Chemical carcinogenesis]. PMID- 3330079 TI - Recent developments in biotechnology: an overview. PMID- 3330081 TI - Special considerations for atypical stainless steel crown situations. PMID- 3330080 TI - Antibiotics Literature Index - A select bibliography. PMID- 3330082 TI - Implants--past, present and future. PMID- 3330083 TI - Production of monoclonal antibody to a 65,000 dalton protein of Mycobacterium leprae. PMID- 3330084 TI - [Clinical approach: evaluation and esthetic in fixed prosthodontics]. PMID- 3330085 TI - [Design of a palatal base for treatment of the partially edentulous in gerontology]. PMID- 3330086 TI - [Evaluation of marginal adaptation of cast ceramic crowns (Dicor)]. PMID- 3330089 TI - The presentation of dynamic concepts in medical education. PMID- 3330087 TI - Adrenal dopamine content of the developing rat. Influence of the thyroid status and insulin-hypoglycaemia. AB - Neonatal hypothyroidism accelerates the postnatal evolution of the adrenal dopamine (DA) content and concentration in the young rat. In 14-day-old control animals, insulin-hypoglycaemia leads to a transient increase in adrenal dopamine content up to 159% above the value in saline-injected animals. This increase is already at its maximum 1 h after insulin administration and lasts 7 h. In the hypothyroid animals, the DA increase evoked by hypoglycaemia is impaired in magnitude (74%) and duration (4 h). PMID- 3330088 TI - Nicotinic acetylcholine receptors in the neurones of autonomic ganglia. PMID- 3330090 TI - The illustration of anatomical atlases during the hand-press era. PMID- 3330091 TI - [The dyslexic child]. AB - Some children go to see an ophthalmologist because they have learning difficulties. Results of the examination being negative, dyslexia should be suspected, as it is known to be a problem for 10% of pupils. The definition, the characteristic signs, and the current pathogenesis data have been examined. The author deplores the fact that the situation in France is so backward: no screening, lack of training of the teaching profession, no specific pedagogical help for the special needs of the dyslexics at school. PMID- 3330093 TI - [Intraocular penetration of antibiotics]. PMID- 3330092 TI - [Orbital localization of clear-cell sarcoma of tendons and aponeuroses. Apropos of a case report]. AB - Clear cell sarcoma of tendons and aponeuroses actually is a well identified soft tissue tumor. A primary orbital involvement is presented, with an optical and electron microscopic study. The orbital topography of such a tumor seems to be an exceptional opportunity. The histological study showed the typical pattern of this clear cell tumor. Ultrastructurally, there are not absolute specific features to establish the diagnosis, except the finding of intra-cellular melanosomes. Histogenesis has been debated for a long time between a melanotic or a synovial origin. According to present knowledge, this tumor may be attributed to a neural crest origin. PMID- 3330094 TI - Immunoregulating peptides II. In vitro effects of TP5 analogs on E-rosette formation and cell division. AB - The effects of seventeen synthetic analogs of thymopentin (TP-5) have been studied in the active and azathioprine-inhibited E-rosette tests. Thymopentin was gradually shortened from the C terminus to peptides and single amino acids. Thymopoietin 32-34 (Arg-Lys-Asp-RGH-0205-TP-3) (II) and thymopoietin 32-35 (Arg Lys-Asp-Val-RGH-0206-TP-4) (I) were the most active peptides. Dipeptide Arg-Lys produced significant stimulatory effect on azathioprine (ED75) inhibited E receptor. Treatment of azathioprine (ED75)-inhibited E-rosette forming cells (ERFC) with arginine or especially lysine increased the number of ERFC. Some of TP-4 analogs decreased further the number of ERFC decreased by azathioprine ED30. These "suppressive" peptides as well as TP-3 caused a partial arrest of K 562 cell proliferation up to 96 hours. Results suggest that TP-5 is not the smallest active fragment of thymopoietins, since peptides (TP-3 and TP-4) exhibit similar or higher T-cell membrane activation on E-receptor. Arginine, lysine, and acidic aspartyl residue seem to be a necessary basic structure to produce a cumulative chemical signal on the activity of T-lymphocytes. PMID- 3330095 TI - The effect of TP-3 (Arg-Lys-Asp), TP-4 (Arg-Lys-Asp-Val), and TP-5 on the metastatic capacity of intravenously injected Lewis lung tumor cells. AB - The oligopeptides Arg-Lys-Asp (TP-3), Arg-Lys-Asp-Val (TP-4), and Arg-Lys-Asp-Val Tyr (TP-5) considered as the active short fragments of thymopoietin were administered (lo mg/kg) to C57B1 mice 24 hours before the intravenous inoculation of Lewis lung tumor (LLT) cells. A substantial decrease in lung metastasis number was observed as a result of treatment with all of the three oligopeptides. TP-3, TP-4, and TP-5 treatment decreased the immunosuppressive activity of Cyclophosphamid (240 mg/kg) given 96 hours before the inoculation of LLT cells. After thymectomy, performed eight days before the LLT inoculation, only TP-3 treatment resulted in the decrease of Cyclophosphamid immunotoxicity. A stimulating effect of TP-3 on T helper cell activity is assumed. The oligopeptides TP-3, TP-4, and TP-5 are recommended for clinical trial in case of malignant tumors and immunodeficiency. PMID- 3330096 TI - [376 amniocenteses performed under continuous ultrasonic control]. AB - The authors report 376 amniocenteses carried out early and late in pregnancy under real time ultrasound at the University Clinic of St Pierre. The ability to watch the needle during the whole procedure of puncture makes it possible, as compared with amniocentesis that has been carried out without ultrasound or without real time ultrasound, to lessen significantly: perinatal mortality (0.26%), several attempts (0.9%) and the risk of accidental haemorrhage (1.6%). Particularly diminished are risks when it would be inevitable to have to put the needle through the placenta (31% of cases). The number of spontaneous abortions linked to the technique has virtually disappeared. When the operator has become very experienced in carrying out amniocentesis under real time ultrasound he becomes much more able to carry out other antenatal diagnostic procedures. Even when for certain indications amniocentesis is replaced by chorion villus biopsy in the first trimester or cord puncture in the third trimester, real-time ultrasound makes it less risky to carry out the procedures and the technique becomes a very useful one in the armamentarium of antenatal diagnostic methods. PMID- 3330097 TI - [Pregnancy toxemia. Review and management]. AB - The author reviews the literature on pre-eclamptic toxaemia, and seeks to ascertain established pathophysiological facts. He points out that the diversity of names used by different authors and in different countries all cover a specific pathological entity, in pregnancy in the human. He looks at causes that may be considered specifically human: the upright position with consequences for the blood circulation, food eaten without regard to the woman's needs, stress factors due to the environment and also to imagination. He considers the relationship between the trophoblast and the maternal body which is specific to pregnancy. From these considerations he describes a synthesis of pathophysiological conditions which give to this specific human disease of pregnancy: One cause: the presence of trophoblasts. Two centres of activity: intravenous disseminated coagulation and platelet activity. Three syndromes: haemodynamic, vascular and renal. Four cardinal signs: albuminuria, raised blood pressure, oedema, hyperuricaemia. Five areas to which prophylaxis, prevention and treatment can be directed: hypovolaemia, hypoalbuminaemia, vasoconstriction, platelet activity, presence of trophoblastic tissue. He suggests a possible sequence for prophylaxis, prevention and treatment to be worked out from these features. PMID- 3330098 TI - [Marfan's disease and pregnancy. Apropos of a case]. AB - Marfan's syndrome is a dominant autosome transmitted disease with different degrees of seriousness. When it is associated with pregnancy there is a considerable increase in the rate of cardio-vascular complications which are responsible for a serious rate of maternal mortality due to aortic dissection. It is therefore very important that the patient, before starting a pregnancy, should be examined very carefully clinically and with ultrasound. A woman with dilatation of the aorta less then 40 mm as measured ultrasonically and who has no major clinical signs can start a pregnancy but even then she should be considered as a high risk case. In other cases therapeutic termination of pregnancy or prophylactic surgical treatment of the condition should be considered. Apart from the serious genetic risks (50%) the risks for the fetus are dominated by prematurity and by fetal death resulting from maternal death. PMID- 3330099 TI - [Normal pregnancy after a Budd-Chiari syndrome treated by shunting: apropos of a case, review of the literature]. AB - A patient who had a meso-atrial by-pass for a Budd-Chiari syndrome a year before conception carried her pregnancy to term. The authors have reviewed the literature. When they had studied the literature the authors took into account cirrhoses of the liver and portal hypertension in association with pregnancy. They concluded that a patient who had had a Budd-Chiari syndrome, particularly when she had also had a porto-caval shunt, was not in principle unable to have a pregnancy. PMID- 3330100 TI - [Management of an ovarian tumor]. PMID- 3330101 TI - [Ultrasonic diagnosis as a decision-making factor in fetal growth retardation (excluding Doppler echocardiography)]. PMID- 3330102 TI - [A new approach to urinary continence disorders in women: urodynamic ultrasonic examination by the vaginal route]. AB - The vesicourethral junction, the urethra cannot be seen when using the abdominal approach because of the interposition of the pubic symphysis. The ultrasonic vaginal approach makes it possible. 53 patients were ultrasonically observed during an urodynamic exploration. The simultaneous utilization of both methods has permit to observe the mechanisms of normal or pathological voiding. When initiating a voluntary micturition, an area (called "prepubic muscle") located in front of the pubic symphysis between the clitoris and the urethral meatus, exert a traction on the periurethral sphincteric area. This sphincteric area, which is well shown by ultrasound, contracts longitudinally (causing shortening of the urethra and opening of the bladder neck) and causes a drop in urethral closure pressure. The increase in the distance between the inferior part of the pubic symphysis and the anterior vaginal wall comes about because of slackening of the elevator ani muscles. This slackening occurs at different times before the bladder contracts. The urethra opens; the complete course of this organ is well defined. Things return to their previous state when voiding finishes. In the case of stress incontinence, the lack of transmission of pressure urodynamically found when the woman is coughing can be seen as a sliding mechanism within the space of Retzius and at the urethro-vesical junction behind the symphysis pubis. The degree of sliding depends on the strength of the cough. In all cases of pure stress incontinence without there being low urethral closure pressure, a maximum stress caused by coughing will produce more than 5 MM sliding before the urethra opens. If the urinary incontinence is due to low urethral closure pressure, the urethra opens without sliding of the urethro-vesical junction whenever the abdominal pressure increases. Urethral instability resembles voluntary voiding but without any voluntary command. "Prepubic" contractions, longitudinal contractions in the sphincteric area and slackening of the levator ani muscles, alone or in association, explain why urethral closure pressure drops. Sometimes this drop is followed by an increase in bladder pressure. PMID- 3330103 TI - [Ultrasonic images the day after voluntary termination of a pregnancy]. AB - We have studied 75 cases of uterine echography, obtained 24 hours after an induced abortion. In 2 out of 3 cases, the uterus was not empty and, in a majority of cases, a pseudo-organized image was observed. The images displayed were a central trans-sonic zone, limited by a line of echoes and containing some echoes which are less or more organized. A few aspects were very difficult to diagnose from a persisting pregnancy. PMID- 3330104 TI - Isolating Campylobacter jejuni in an atmosphere made oxygen deficient using pyrogallol in a candle jar. PMID- 3330105 TI - Pathogens associated with acute enteritis in Brazilian children. PMID- 3330106 TI - Campylobacter: a synopsis. PMID- 3330107 TI - Xylose lysine desoxycholate agar for recovering Shigella dysenteriae 1 and Shigella flexneri from faeces. PMID- 3330109 TI - [Molecular mechanism for gene expression in kininkallikrein system]. PMID- 3330110 TI - [Albumin, a biovehicle for amphipathic molecules]. PMID- 3330108 TI - Generation and characterization of a murine monoclonal antibody specific for the human T1-CD5 molecule. AB - Murine monoclonal antibodies (MoAbs) have found widespread applications in the characterization of the molecular and functional features of lymphocyte differentiation antigens. The present paper summarizes the results of our work dealing with the production and selection of a murine MoAb recognizing a molecule expressed during the whole differentiative life of T lymphocytes. The MoAb CB01 resulted to be specific for an apparently unique epitope of the T-cell specific membrane glycoprotein T1-CD5. PMID- 3330111 TI - [Eukaryotic secretory genes: from yeast to mammalian cells]. PMID- 3330112 TI - [Tissue-specific expression and regulation of opioid peptide precursor genes]. PMID- 3330113 TI - Regression of the atherosclerotic lesion in man: the impact of noninvasive techniques. AB - Experimental studies demonstrate that atherosclerotic plaques induced in animals can regress following appropriate treatment, but evidence in favour of the regression of atherosclerotic lesions in man is still scanty. New imaging techniques, such as high resolution B-mode echotomography, allow the visualization and measurement of anatomical parameters of the arterial wall in sample arteries of human patients "in vivo", introducing the possibility of a much more precise monitoring of early atherosclerotic lesions. New information on the natural history of atherosclerotic disease in man, including the possibility of differentiating between lesions of different clinical significance, can be expected from the wide application of these techniques to atherosclerosis research. A more precise testing of diets, drugs and physical procedures intended to obtain the regression of atherosclerosis in human beings will also be possible. PMID- 3330114 TI - Lipoprotein abnormalities and extracoronary atherosclerosis in patients with premature ischemic heart disease. AB - A study of serum lipoprotein (VLDL, LDL, HDL) concentration has been performed on 36 males who had undergone an aorto-coronary bypass operation before age 50. They have been compared to 33 healthy men in the same age range. The presence and severity of coronary, carotid and peripheral atherosclerosis in these patients has been evaluated on the basis of coronary angiograms, continuous wave Doppler and Duplex scanning by echo-Doppler. Lipoprotein abnormalities have been related to the occurrence of extracoronary arterial lesions in association with myocardial ischemia. Total serum cholesterol and triglycerides, LDL cholesterol and triglycerides were higher in IHD patients (p less than 0.05), while HDL cholesterol was lower (p less than 0.01). No statistically significant difference was detected in VLDL lipids or apo B and in LDL apo B. Signs of extracoronary atherosclerosis were more frequent among IHD patients than in controls. Ankle/arm pressure ratio was abnormally low in 12 patients as compared to only one control (p less than 0.01). Echo-Doppler examinations of iliac arteries demonstrated a higher prevalence of lesions among IHD patients as compared to controls (20 versus 2; p less than 0.01). All patients (4 out of 36) with audible carotid bruits had stenoses in the internal carotid artery. In order to evaluate the relationships between lipoprotein concentration and occurrence of extracoronary atherosclerosis, analysis of variance and multiple comparisons were performed on values for lipoprotein concentration in three groups: controls, IHD patients without evidence of extracoronary atherosclerosis, IHD patients with detectable extracoronary lesions. Significant differences among the three groups were demonstrated as regard to LDL cholesterol or triglycerides and HDL cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3330115 TI - Metabolic approach to the diagnosis and treatment of atherosclerotic peripheral vascular disease. AB - Metabolic and clinical peculiarities of patients with peripheral vascular disease (PVD) were evaluated in two studies. In the first study lipid and lipoprotein composition of 20 patients with PVD were examined. Twelve of these patients were normolipidemic, the other 8 hypertriglyceridemic. Ten normolipidemic and ten hyperlipidemic age-matched subjects served as controls. High density lipoprotein cholesterol (HDL-C) levels were markedly reduced in the hypertriglyceridemic, both with (35.1 +/- 5.0 mg/dl) and without (36.2 +/- 11.7 mg/dl) PVD as compared to the normolipidemic patients (47.0 +/- 6.3 mg/dl) and controls (48.1 +/- 10 mg/dl). All the PVD patients showed an increased apolipoprotein B content in the very low density lipoproteins (VLDL) as compared to controls (p less than 0.001). A significant correlation between VLDL-cholesterol and apo B levels was detected in both groups; however, two distinct populations could be clearly separated (slopes of the regression lines: PVD patients = 0.350; controls = 0.215, p less than 0.0001). These data suggest a possible discriminatory power of VLDL-apo B levels in PVD patients independent of other metabolic parameters. In the second study, the clinical activity of metformin (N, N-dimethylbiguanide) a widely used antidiabetic agent, on arterial blood flow was evaluated in 15 patients with PVD. Flow was determined by quantitative strain-gauge plethysmography during a cross over trial, comparing 6 months of drug and placebo administration. Metformin (850 mg tid) significantly increased arterial flow after a standardized ischemia in both sequences. In spite of the minimal changes of plasma lipid levels during metformin, a highly significant increase of HDL-C levels (+8.3% during the whole treatment) was demonstrated. Plasma levels of isoprotein AI-1 were also raised during the metformin period. Although the mechanism/s of the beneficial effects of metformin on flow cannot, at present be defined, the reported results underline the significant therapeutic potential of this metabolic drug treatment in PVD. PMID- 3330116 TI - Slow release nifedipine in the treatment of Raynaud's phenomenon. AB - An ever increasing interest is shown towards calcium-antagonist drugs and in particular to nifedipine in the treatment of Raynaud's Phenomenon (R.P.) On this matter a randomized double-blind study with 40 mg/die slow release nifedipine versus placebo was carried out for 30 days on 24 patients affected by R.P. idiopathic in 16 cases and secondary in the remaining 8 cases. The evaluation of the clinical situation (hand ischemic attacks, pain, skin trophism) and the structural one (capillaroscopy of the finger nail bed and strain-gauge digital plethysmography) could be performed on 17 patients since 7 dropped out. From the clinical point of view an improvement was observed especially in the reduction of the ischemic attacks (88.8% of patients treated with nifedipine vs. 25.0% treated with placebo). Capillaroscopic results showed an improvement in 100% of the cases treated with nifedipine vs. 12.5% with placebo (p less than 0.001), as well as an improvement of the basal digit blood pressure values and after cold test in 88.8% of patients treated with nifedipine vs. 12.5% treated with placebo (p less than 0.005) and (p less than 0.0025) respectively. PMID- 3330117 TI - Direct and indirect evaluation of lesions obstructing the carotid bifurcation. A comparison of Doppler spectrum analysis with angiography. AB - The diagnostic accuracy of real-time continuous wave (c.w.) Doppler spectrum analysis and of indirect periorbital Doppler examination for detecting carotid bifurcation disease was evaluated. The results of non-invasive studies were compared with contrast arteriograms of patients studied for symptomatic cerebrovascular disease (91%) or for asymptomatic bruits (9%). Periorbital examination was insensitive to less than 75% carotid stenoses and sensitivity to severe stenoses or occlusions was respectively 56% and 85% (mean 73%). Mean sensitivity of real-time C.W. Doppler spectrum was 93% and sensitivity to stenoses of less than 45% diameter reduction was equal to 76%, while specificity in identifying normal carotid arteries was 89% for an accuracy of the method of 91%. Positive and negative predicting values were respectively 89% and 93%. Direct Doppler interrogation of the carotid arteries with real-time C.W. Doppler spectrum analysis was able to distinguish operable stenoses from inoperable occlusions in 87% of the cases. PMID- 3330118 TI - Surgical approach to combined carotids and coronaries lesions. AB - A preoperative carotid evaluation by a Duplex Scanner ATL Mark V has been carried out in 338 patients candidates to CABG. When a critical lesion was detected a digital angiography was subsequently performed. In 19 patients an operation was done because the coexistence of lesions in the carotids and the coronaries. The indications, the timing of the operations and the surgical approach are discussed. In the Author's minds the combined procedure seems to be advisable. PMID- 3330119 TI - Cross-over axillary by-pass. Treatment of subclavian or innominate artery obstructive lesions. AB - A 13-year experience consisting on 16 consecutive patients submitted to axillary to-contralateral artery by-pass in the treatment of obstructive lesions of the subclavian or innominate artery is reported. Nine patients complained of typical subclavian steal syndrome. Extended patency with very satisfactory functional result was achieved in twelve patients. An extensive survey is made of the results of such procedure, as reported in the literature. The theoretical advantages in comparison with other kinds of extrathoracic procedures aiming at the same goal are briefly outlined. PMID- 3330120 TI - [Clinical aspects of myelopathy]. PMID- 3330122 TI - [Long-term follow-up of an autopsy case of Caroli's disease]. PMID- 3330121 TI - [Nine cases of adult-onset Still's disease: diagnostic problem and comparison of clinical features between Japanese and foreign cases]. PMID- 3330123 TI - [A case of non-familial hypophosphatemic vitamin D resistant osteomalacia presenting in adolescence]. PMID- 3330124 TI - [A case of hypoglycemic attack associated with sulfamethoxazole-trimethoprim]. PMID- 3330125 TI - Current management of urolithiasis in the spinal cord injury patient. PMID- 3330126 TI - Active specific immunotherapy of renal cell carcinoma patients: a prospective randomized study of hormono-immuno-versus hormonotherapy. Preliminary report of immunological and clinical aspects. AB - Early results of a prospective, randomized trial of active, specific immunotherapy adjunctive to nephrectomy in all stages of RCC are presented. Forty three patients with median followup of 30 m, who were randomly allocated to either immuno-hormonotherapy arm (IMT), or hormonotherapy alone (HT), are evaluated in terms of progression-free interval (PFI) and overall survival by life table method. Immunotherapy consisted of autologous irradiated tumor cells (AITC), admixed with bacillus Calmette-Guerin (Glaxo) administered by the intradermal and endolymphatic route. Clinical results of this study show only a trend for advantage of the experimental (IMT) arm over the control (HT) arm, this trend did not reach statistical significance level: prolongation of disease free period in stages I-III with localized disease (p less than 0.1) and prolongation of survival in patients with metastatic disease (p less than 0.07). A correlation was established between induction of cutaneous delayed hypersensitivity (DTH) to AITC and prolonged PFI and survival: patients with positive DTH had a significantly better course of disease than those who could not be converted to positivity after repeated immunizations. Positive in vitro leukocyte migration inhibition against autologous tumor preparations correlates well with positive in vivo cutaneous DTH. Some immunological aspects of active immunization with autologous tumor cells are discussed. PMID- 3330127 TI - A sensitive, rapid assay for the detection of human granulocyte-macrophage colony stimulating factor. AB - Several monoclonal antibodies were developed against recombinant human granulocyte colony stimulating factor (hu-GM-CSF). All were reactive to the protein by enzyme linked immunoabsorbent assay (ELISA), and one, 1G2 was capable of immunoprecipitating significant levels of radiolabeled hu-GM-CSF. When 1G2 and a second GM-CSF reactive monoclonal antibody, 3G11, were used in a double determinant assay, the level of detection of hu-GM-CSF in solution was approximately 500 ng/ml. Additional sensitivity was gained by using affinity purified rabbit polyclonal antibodies, together with the monoclonal 1G2. Using such a configuration in a double determinant assay one could detect 10-90 ng/ml of human-GM-CSF in solution with no reactivity observed to CSF-1 or granulocyte CSF. PMID- 3330128 TI - [Mechanical properties of the human vocal fold elicited by a single rectangular pulse--damping ratio]. PMID- 3330130 TI - [The transformation of E. coli recB recC sbcB with colE1 type plasmid is inhibited by the transcription of cea gene]. PMID- 3330129 TI - [Structure and function of serum lipoprotein]. PMID- 3330131 TI - [Fibronectin, structure and properties: current concepts]. PMID- 3330132 TI - [Current concepts in periodontology]. PMID- 3330133 TI - [Ultrasonic curettage with aluminum chloride irrigation in treatment of adult periodontitis. Clinical study over a 1 year period]. PMID- 3330134 TI - [Subgingival use of chlorhexidine in the treatment of periodontitis]. PMID- 3330135 TI - [The place of gingivitis in the current concept of periodontal disease]. PMID- 3330136 TI - [The "sandwich" technic. Why use glass ionomers in esthetic dentistry]. PMID- 3330137 TI - [Anatomical and functional concepts of the inlay-core]. PMID- 3330138 TI - [Computerized instruction in diagnosis]. PMID- 3330139 TI - The Institute of Naval Medicine. PMID- 3330140 TI - Comparative trial of azapropazone and indomethacin plus allopurinol in acute gout and hyperuricaemia. AB - This study compared the effects of azapropazone and indomethacin plus allopurinol in the management of acute gout and hyperuricaemia. A group of 93 patients predominantly based in general practice were randomly allocated to the two treatment regimens (azapropazone (days 1-225) or indomethacin (1-28) followed by allopurinol (29-225)) on a double-blind double dummy basis. Azapropazone produced a substantial reduction in serum uric acid levels by day 4 compared with day 1 (P<0.002) and was superior to indomethacin with regard to recorded levels of serum uric acid at day 4 (P<0.01) and day 28 (P<0.05). From day 28 onwards allopurinol produced and azapropazone maintained similar reductions in serum uric acid. Both treatments rapidly controlled the initial acute attacks of gout and both produced side effects similar in frequency and nature. Fewer breakthrough attacks of gout occurred in the azapropazone group (12) than the indomethacin/allopurinol group (21).Although the results achieved in both treatment groups were similar it has been shown that azapropazone is effective monotherapy for controlling both acute attacks of gout and hyperuricaemia. PMID- 3330141 TI - [Clinical observations of 30 patients with acute promyelocytic leukemia]. PMID- 3330142 TI - [Determination of calcium, magnesium, iron and copper in serum by flame atomic absorption spectrophotometry]. PMID- 3330143 TI - [Experience of surgical treatment of pheochromocytoma--report of 3 cases]. PMID- 3330144 TI - [The levels of serum Zn, Cu, Fe, Ca, Mg of school-age children in Kaohsiung and the off-shore Island of Penghu]. PMID- 3330145 TI - The pathogenesis of experimental arteritis induced by Candida alkali-extract in mice. AB - The pathogenesis of experimental arteritis induced by Candida alkali-extract in mice was studied from the immunological, pharmacological and chemical points of view. The following results were obtained. 1) The incidence of arteritis increased in parallel with IgE antibody level of Candida, as shown by the PCA method. 2) Candida polysaccharide showed cardiotonic, coronary vasodilatatory and vasoconstrictive activities on Langendorff's and spiral preparation of rats. 3) Candida polysaccharide was shown to contain digitoxose by gas-mass spectrometry. From these results, it is suspected that this extract reacts on experimental animals by the toxic and immunological mechanisms, and that these mechanisms may be related to the occurrence of arteritis. PMID- 3330146 TI - Colonization of the intestinal tract of mice with Clostridium tetani. AB - Colonization of intragastrically inoculated Clostridium tetani in intestinal tract of mice was investigated by cultivation of daily stool samples and quantification of the bacilli over a period of 3 weeks. We found that most of the inoculum was excreted in the stool during the first 24 hr. The amount of C. tetani recovered on the second day after inoculation was very small. C. tetani apparently thrived in the intestinal tract when more than 6 log colony forming units (CFU) of tetanus spores had been inoculated. Otherwise, C. tetani colonized poorly in intestinal tract. Tetanus toxin was not detected in the stool nor in the contents of the small and large intestines 24 hr after 6.23 log CFU of tetanus spores had been inoculated. We concluded that the intestinal cavity of mouse is not a favorable environment for colonization of C. tetani under natural conditions. PMID- 3330147 TI - [The analysis of tumor growth pattern by endoscopic ultrasonography in patients with depressed type of gastric cancer]. PMID- 3330148 TI - [A case report of splenic hamartoma]. PMID- 3330149 TI - [Kidney functions and fluid replacement therapy immediately after living-donor transplantation for pediatric recipients]. PMID- 3330151 TI - [Clinical studies on renal cell carcinoma as an incidental finding]. PMID- 3330150 TI - [Clinical course of beta 2-microglobulin in the plasma of patients suffering from chronic renal failure under conservative therapy in relation to oral adsorbent therapy]. PMID- 3330153 TI - [Diagnosis of the invasion of uterine cervical cancer to the bladder by transurethral ultrasonography and cystoscopy]. PMID- 3330152 TI - [Study on 25 cases of renal cell carcinoma discovered by ultrasonography]. PMID- 3330154 TI - [Intravenous digital subtraction angiography for evaluation of urogenital disease]. PMID- 3330155 TI - [Papillary cystadenocarcinoma of the prostate; report of a case]. PMID- 3330156 TI - [Effectiveness of lidocaine in the prevention of primary ventricular fibrillation in acute myocardial infarction. Multiple initial intravenous doses of the drug]. PMID- 3330158 TI - [Ischemic heart disease--a pathologist's point of view]. PMID- 3330157 TI - [Evaluation of the preparation Cordafen (Polfa) in the treatment of angina pectoris in patients after myocardial infarction]. PMID- 3330159 TI - [The kinesthetic theory of vision and the practical application of various methods of treatment of strabismus. A paper dedicated to the memory of Prof. Witold Starkiewicz]. PMID- 3330161 TI - [The Cuppers suture in the treatment of congenital nystagmus]. PMID- 3330160 TI - [The Schepens suture in the surgery of the oculomotor muscles]. PMID- 3330162 TI - [Infections after surgical treatment of strabismus]. PMID- 3330163 TI - Exocrine and endocrine pancreatic functions in children with the short bowel syndrome. PMID- 3330164 TI - The response of gastroenteropancreatic hormones following an oral water load in non-insulin dependent diabetes mellitus. PMID- 3330165 TI - Polish historical collection in the Erskine Medical Library, University of Edinburgh. PMID- 3330166 TI - Beginnings of apothecaries organizations in old Poland. PMID- 3330167 TI - Professor Benedykt Dybowski, M.D. (1833-1930): physician and discoverer of the East Siberian Fauna. PMID- 3330168 TI - Dental sintering: labor-saving innovation in C&B fabrication. PMID- 3330169 TI - Hormonal regulation of lymphocyte functions. AB - The role of hormones in regulating the complex network of immune responses has lately been emphasized. In particular, glucocorticoids and sex hormones have been shown to modulate both cellular and humoral immunity. Reports concerning the mechanisms of hormonal action are still somewhat conflicting, and there are reports of both inhibitory and stimulatory effects on various phases of the immune response. PMID- 3330170 TI - Immunobiology of acute graft-versus-host disease. AB - Acute graft-versus-host disease (aGVHD) remains one of the major obstacles in bone marrow transplantation. The histological changes of aGVHD have been documented thoroughly; much less is known about the inflammatory cell populations causing the reaction. This review focuses on the inflammatory cells isolated from the different target organs during aGVHD. PMID- 3330171 TI - Influence of verapamil on central and peripheral effects of prostacyclin on circulatory system in rats. AB - The influence of verapamil on cardiovascular effects of prostacyclin (PGI2) in rats was examined. PGI2 administered into the lateral brain ventricle (i.c.v.) or intravenously (i.v.) in a dose of 2.7 x 10(-8)mol evoked hypotension and tachycardia. Pretreatment with verapamil in a dose of 2.0 x 10(-5)mol/kg given intraperitoneally (i.p.) diminished hypotensive effect of PGI2 i.c.v. as well as inhibiting the influence of PGI2 i.c.v. and i.v. upon the heart rate. Bolus injection of PGI2 in a dose of 2.7 x 10(-10), 2.7 x 10(-9) or 2.7 x 10(-8)mol evoked biphasic inotropic and chronotropic effects on isolated rat heart. Short term increase of the contractile force together with bradycardia and afterwards long-lasting decrease of contractility with sustained, slight tachycardia were observed. Verapamil in a concentration of 1.0 x 10(-6)M blocked biphasic inotropic effect and bradycardia after PGI2 administration. Because some central and peripheral cardiovascular effects of PGI2 were inhibited by verapamil, it is concluded that PGI2 may participate in transmembrane calcium ions movements. PMID- 3330173 TI - Sperm chromatin decondensation after fertilization. PMID- 3330172 TI - Extraction and quantitation of total cholesterol, dolichol and dolichyl phosphate from mammalian liver. AB - A procedure is described for the determination of total cholesterol, dolichol and dolichyl phosphate (Dol-P) in mammalian liver. It is based on extraction of these compounds into diethyl ether after alkaline saponification of the tissue. Extractability is affected by the length of saponification and concentration of potassium hydroxide (KOH) in the saponification mixture. After extraction, total cholesterol and dolichol are quantitated directly by reverse-phase high pressure liquid chromatography (HPLC) on C18. Dol-P requires further purification before quantitation by HPLC, this is accomplished by chromatography on silicic acid. These methods gave recoveries of over 90% for cholesterol and dolichol and about 60% for Dol-P, using [4-14C]cholesterol, a polyprenol containing 15 isoprene units, and [1-14C]Dol-P as recovery standards. Concentrations of total cholesterol, dolichol and Dol-P in livers from one month-old-CBA mice were found to be 5.7 +/- 0.7 mg/g, 66.3 +/- 1.2 micrograms/g and 3.7 +/- 0.3 micrograms/g, respectively. PMID- 3330174 TI - Temperature-sensitive growth mutants as live vaccines against experimental murine salmonellosis. AB - Temperature-sensitive growth mutants of Salmonella enteritidis, NUB 209 and NUB 323, characterized as protein synthesis mutants, were unable to proliferate at 37 C and lost the parent's virulence. In mice, these mutants conferred high levels of protection as live vaccines. Although the vaccination effect of NUB 323 was not so good as that of NUB 209, NUB 323 was preferred as a safer live vaccine because this mutant was completely avirulent and no back mutation appeared. PMID- 3330175 TI - [Renin and hypertension]. PMID- 3330176 TI - [Ernst Grafenberg--the inventor of the intrauterine coil]. PMID- 3330178 TI - Improving the mental health of black Americans: lessons from the community mental health movement. AB - The ideology of the community mental health movement in the 1960s--that psychological distress among black Americans could be prevented if policies moved away from clinical models to a focus on social-structural change--still has much to offer. Agendas for both epidemiologic and intervention research will have to address the antecedents of psychopathology and assess the strategies of adjustment to social mobility and expectancy problems. Long-term preventive programs aimed at preschool and elementary school and at job training offer the greatest promise. PMID- 3330177 TI - Paying the price: medical care, minorities, and the newly competitive health care system. AB - The newly competitive health care system reflects both an excess supply of health care providers and a greater sensitivity to price among those purchasing health services. These dual pressures are felt in public programs as well as in private markets. A competitive ethos is also changing popular expectations of the appropriate relation between health care institutions and their communities. These changes offer opportunities for enhanced access to health care for some black Americans, but portend dire restrictions on access for the least-advantaged blacks. They also threaten to reduce significantly the influence exerted by black communities over their local health care providers. PMID- 3330179 TI - The health, physical functioning, and informal supports of the black elderly. AB - Among the elderly population, blacks are increasing more rapidly--and perhaps differently--than whites. Cross-sectional data from two unique surveys describe their heterogeneity in health, physical functioning, and social networks at "younger," middle, and "older" ages. The relation between age and these factors may be nonlinear; indeed, evidence supports the contention of a racial "crossover" at advanced ages. Life experiences--ecological, social, economic, and familial--of successive cohorts are likely to pose different problems for elderly blacks in the future. Further research into these differences should inform public policy. PMID- 3330180 TI - [Very low birth weight neonates: from perinatal care to neurological follow-up. I. Review of the world literature]. PMID- 3330181 TI - Magnetic resonance imaging. PMID- 3330182 TI - Comparison of sublingual and oral prazepam in normal subjects. I. Clinical data. AB - Five normal volunteers received at a 2-week interval a single dose of sublingual or oral prazepam in double-blind and cross-over conditions. All subjects completed a battery of 15 visual analogue scales before drug intake and 7.5, 15, 22.5, 30, 45, 60, 90 min, 2, 3, 5, 6, 7, 8, 9, 10 and 24 h following intake whereas a computerized assessment of vigilance (reaction time) was performed before intake, 15, 30, 60 min, 2, 3, 6, 8, 10 h following intake. Subjects rated themselves significantly more feeble, clumsy, lethargic, and incompetent following sublingual as compared to oral prazepam while a trend in the same direction was noted for the adjectives muzzy and mentally slow. In contrast, reaction time did not exhibit significantly different changes over time between the two forms. These results suggest a subjectively more rapid onset of activity following sublingual compared to oral prazepam. PMID- 3330183 TI - Platelet serotonin uptake and effects of vitamin B6-treatment in premenstrual tension. AB - The platelet serotonin uptake kinetics was studied in 19 women with premenstrual tension syndrome (PMS) and 19 age-matched symptom-free controls during the pre- and postmenstrual phases. Both groups exhibited stable Vmax and Km values at the two phases of the menstrual cycle. There were no differences between the two groups regarding the level of Vmax and Km, respectively. The effect of season (p less than 0.001), with lowered values of Vmax during spring compared to corresponding values during the later half of the year, was identical in both groups. A tendency to lowered Vmax values in the follicular phase in women with PMS during spring may indicate that women with PMS are more vulnerable to developing depressive episodes during this period than symptom-free women. The blood platelet count in whole blood was decreased in the luteal phase in the control group but remained stable in the PMS group. The effect of vitamin B6 on clinical symptoms and the platelet serotonin uptake during the luteal phase was investigated in a double-blind crossover design. Vitamin B6 treatment did not significantly improve the PMS symptoms. There was no effect of treatment on Km. Vmax increased significantly in response to treatment (F = 9.6; p less than 0.001) in both groups, but there was no significant difference between placebo and vitamin B6. PMID- 3330184 TI - Psychotropic drug profiles: comparisons by topographic maps of absolute power. AB - In a double-blind fourfold crossover design, 11 subjects were randomly assigned to placebo, 10 mg diazepam, 75 mg amitriptyline, and 75 mg chlorpromazine. During a simple vigilance task, 12 midline and left hemisphere leads were recorded before and 3 h after drug administration. The EEG was quantified by spectrum analysis, the topographic structure displayed by brain mapping techniques, and the results compared with earlier studies which used the same design and drugs. Diazepam showed the expected increase in beta; however, fast beta was increased as much as slow beta. Amitriptyline showed an increase of slow wave power and a reduction of alpha. In contrast to earlier studies, a decrease of fast beta was found. In addition, the spatial pattern of alpha changed from an occipital to a parietal maximum. Chlorpromazine showed an increase in the theta band. In occipital regions, there was a small decrease of fast beta; however, centrally there was an increase of both slow and fast beta. These results were confirmed by a multivariate analysis of variance. PMID- 3330186 TI - Hypokalaemic and electrocardiographic effects of aminophylline and salbutamol in obstructive airways disease. AB - The hypokalaemic and electrocardiographic effects of nebulised salbutamol (2.35 mg x 2, 120 min apart) and intravenous aminophylline (6 mg/kg followed by 0.5 mg/kg/hr infusion) alone and in combination, were investigated in eight patients with stable asthma. Both agents produced significant hypokalaemia, mean maximum for salbutamol 0.55 mmol/l, mean maximum for aminophylline 0.29 mmol/l. Salbutamol increased the QTc interval and depressed T-wave amplitude whilst aminophylline decreased PR interval. These effects were increased when they were given in combination but were highly variable between individuals. It is likely that arrhythmias may be precipitated in patients with hypoxaemia, acidosis or those with preexisting cardiovascular disease. PMID- 3330185 TI - Inhaled high-dose beclomethasone in chronic asthma. AB - The effects of high-dose inhaled beclomethasone dipropionate were studied retrospectively in 123 asthma patients who were inadequately controlled on standard doses of beclomethasone dipropionate, or who required oral corticosteroids to control their asthma. High-dose beclomethasone dipropionate was administered by aerosol which delivered 250 micrograms beclomethasone dipropionate per metered dose. Thirty-one percent of the steroid-dependent patients (n = 65) were able to stop maintenance oral steroid after the introduction of beclomethasone dipropionate 250 and a further 48% were able to reduce their daily dosage. The mean reduction in daily maintenance prednisone was 5.2 mg. Comparing a six month period before and during treatment with beclomethasone dipropionate 250, asthma control was improved in 69% of all patients. This was accompanied by a 53% reduction in the number of acute attacks requiring supplementary courses of oral corticosteroid and a 70% reduction in admissions to hospital. Prior to beclomethasone dipropionate 250, 21% of the steroid-dependent patients were maintained on alternate day prednisone whereas after the introduction of beclomethasone dipropionate 250, 44% of those 45 still requiring continuous prednisone were maintained on an alternate-day regimen. PMID- 3330187 TI - Adenocarcinoma of the appendix: case report. AB - A patient with adenocarcinoma of the appendix is reported who presented with the symptoms of acute appendicitis. The literature is reviewed. PMID- 3330188 TI - A controlled trial of pentoxifylline (Trental 400) in intermittent claudication: clinical, haemostatic and rheological effects. AB - A formulation of pentoxifylline (Trental 400) has been claimed to increase claudication distance by improving red cell deformability and decreasing blood viscosity and platelet aggregation. In order to test this claim 30 stable claudicants recruited from one population took part in a double-blind randomised trial of placebo versus pentoxifylline. Both placebo and pentoxifylline treated patients improved subjectively and increased their claudication distance over the study period. Analysis of the blood results showed that the only apparent change was a tendency towards increased red cell filtration in the group treated with pentoxifylline; but no significant difference was found between claudicants and normal controls in the degree of red cell filterability nor did red cell filterability correlate with claudication distance. Pentoxifylline did not affect claudication distance or have any useful effect on blood flow properties, calling into question both its efficacy and suggested mode of action. PMID- 3330189 TI - Fifty years of health research. PMID- 3330190 TI - The decline in stroke mortality: the limited role of antihypertensive therapy. PMID- 3330191 TI - The champions of tonsillectomy. PMID- 3330192 TI - [In memory of Prof. Jaroslaw Iwaszkiewicz (1906-1985)]. PMID- 3330193 TI - [In memory of Dr. Tadeusz Gerwel]. PMID- 3330194 TI - [Torsion of the ovary in children: value of echography and difficulties of anatomical interpretation]. AB - Two cases with the clinical presentation of peritonitis and a 9 year-old girl with ovarian torsion are reported: a 2 year-old girl with paroxistic abdominal pain and occlusive syndrome. Ultrasonography was of main interest in that situation. The necrotized ovary was extracted at intervention in both cases; histological data did not allow to distinguish the torsion on an hemangiomatous ovary from the torsion of an healthy ovary, which represents an exceptional feature. PMID- 3330196 TI - The representation of nonuniform motion: induced movement. AB - Induced motion occurs when there is a misallocation of nonuniform motion. Theories of induced motion are reviewed with respect to the model for uniform motion recently proposed by Swanston, Wade, and Day. Theories based on single processes operating at one of the retinocentric, orbitocentric, egocentric, or geocentric levels are not able to account for all aspects of the phenomenon. It is therefore suggested that induced motion is a consequence of combining two different types of motion signals: one provides information by registering the motion with respect to the retina, orbit, and egocentre; the other provides information only on the relational motions between the pattern elements. Simple rules are given for defining a frame of reference for the relational motion process, which can result in a reallocation of the motion signals. It is proposed that the two signals in combination are weighted differentially, with the greater influence coming from the relational signals. Procedures for determining the weighting factors are described, and predictions from the model are examined. PMID- 3330195 TI - [Diagnosis and follow-up of Russel's diencephalic cachexia by echography, x-ray computed tomography and nuclear magnetic resonance]. AB - A diencephalic astrocytoma was diagnosed by ultrasonography in a 5 months old girl with nystagmus and emaciation. A 27 months follow-up with ultrasonography, computed tomography and magnetic resonance imaging, showed an initial improvement after irradiation and afterwards the development of complications with ventricular dilatation and parenchymal calcifications. PMID- 3330197 TI - [Combined examination using rhenium-sulfur colloid, HEPIDA complex and ultrasonography in the evaluation of focal changes in the liver]. PMID- 3330198 TI - [Osteoblastic neoplastic and neoplasm-like bone changes. II. Osteoblastoma and its place in the classification]. PMID- 3330200 TI - [Changes in the lungs in patients with transplanted kidneys]. PMID- 3330201 TI - [Value of ultrasonic examination in locating pheochromocytoma]. PMID- 3330199 TI - [Use of digital subtraction angiography in the examination of the abdominal aorta]. PMID- 3330203 TI - [Evaluation of the first 5 years (1981-1985) of the use of MR tomography]. PMID- 3330202 TI - [Protein-bloc, a new contrast embolization material. Experimental studies]. PMID- 3330204 TI - [Brief outline of the development of radiology in Poznan 1896-1986]. PMID- 3330205 TI - [Use of contrast ultrasonography in the diagnosis of uterovesical fistula]. PMID- 3330206 TI - [Value of scintigraphic examination using I-131-MIBG in locating pheochromocytoma in the mediastinum. Case report]. PMID- 3330208 TI - [Evaluation of the patency of extracranial segments of the carotid arteries. Diagnostic accuracy of presently used methods]. PMID- 3330207 TI - [Technics and methods of radiological examination and progress in the surgical treatment of dental loss by implants and transplants]. PMID- 3330209 TI - [Usefulness of computerized tomography in the preoperative diagnosis of intracranial aneurysms]. PMID- 3330210 TI - [Computerized-tomographic studies of tumors of the mouth floor and areas anatomically adjacent. I. Methods of examination and radiological anatomy]. PMID- 3330211 TI - [Diagnostic possibilities of computerized tomography of the orbit]. PMID- 3330212 TI - [Technical possibilities of present-day equipment in computerized-tomographic examination of the orbit]. PMID- 3330213 TI - [Early changes in the thorax after heart surgery in radiological images]. PMID- 3330215 TI - [Participation of the kidneys in the biotransformation of narcotics]. PMID- 3330214 TI - [Radiological examination of patients after laryngopharyngoesophagectomy with simultaneous reconstruction of the digestive tract using a free autologous transplant of the small intestine]. PMID- 3330216 TI - [Attempts at the treatment of acquired immunodeficiency syndrome (AIDS)]. PMID- 3330217 TI - [Acquired immunodeficiency syndrome seen in Africa]. PMID- 3330218 TI - [Epidemiology of leukemia. II. Multifactorial pathogenesis]. PMID- 3330219 TI - [Kunin's antigen (ECA)]. PMID- 3330220 TI - [Effect of dietary deficiencies on the host's immune system and the course of parasitic infections]. PMID- 3330221 TI - [Progress in the biology and therapy of myelocytic leukemia]. PMID- 3330222 TI - [Characteristics of immunological phenomena in hepatitis B virus (HBV) infection]. PMID- 3330223 TI - [Oligoclonal and polyclonal gamma globulin bands in the cerebrospinal fluid in subacute sclerosing panencephalitis, multiple sclerosis and congenital infections of the central nervous system]. PMID- 3330224 TI - [Transforming growth factors]. PMID- 3330225 TI - [The 1986 Nobel Prize for medicine]. PMID- 3330226 TI - [Muramyl peptides and their pharmacological properties]. PMID- 3330227 TI - [Cystatins]. PMID- 3330228 TI - [Regulation of enzyme activity through formation of mixed protein disulfides]. PMID- 3330229 TI - [Heterogeneity of the oligosaccharide structure of N-glycoproteins as a result of the cotranslational processes]. PMID- 3330230 TI - [Transfer RNA genes: their organization and expression]. PMID- 3330231 TI - Lymphocyte subpopulations. PMID- 3330233 TI - Intranasal squamous cell carcinoma in a renal transplant recipient on long term immunosuppression. AB - An increased risk of developing malignant disease after renal transplantation and immunosuppression with azathioprine and corticosteroids is well documented. We report a case of intranasal carcinoma occurring in a renal transplant recipient. The possible role of immunosuppression on the development and on the outcome of treatment of this tumour is discussed. PMID- 3330232 TI - Ethnic differences in respiratory diseases. PMID- 3330234 TI - The spectrum of schizophrenia. PMID- 3330235 TI - Extra-corporeal shock wave lithotripsy. AB - Extra-corporeal shock wave lithotripsy (ESWL) has proved to be a revolutionary advance in the treatment of renal stone disease. It, itself, is non-invasive but may necessitate or be used as an adjunct to more invasive auxiliary procedures. The basic principles of lithotripsy, the clinical experience thus far and probable future applications are discussed. PMID- 3330236 TI - Immediate versus deferred treatment for early prostatic cancer. AB - The diagnosis of early (non-metastatic) prostatic cancer is dependent upon the patient presenting himself with symptoms or for routine rectal examination or ultrasound screening. Diagnosis in the absence of symptoms is more common outside the United Kingdom and as a result the opportunity to treat such patients occurs more commonly in other countries. The treatment options for the different stages are reviewed and the evidence for their effectiveness is considered. A review of the literature yields conflicting evidence of the efficacy of and the necessity to institute early therapy. This basic gap in our current knowledge should be filled when the results of the existing Medical Research Council (MRC) clinical trial of immediate and deferred orchidectomy are available. PMID- 3330239 TI - Screening for early post-gastrectomy osteomalacia. PMID- 3330238 TI - Epilepsy in the elderly. PMID- 3330240 TI - Predictive values. PMID- 3330237 TI - Colony-stimulating factors in the pathogenesis and treatment of disease. PMID- 3330241 TI - Obstructive sleep apnoea. PMID- 3330242 TI - [Comparison of 2 different blood culture systems: liquoid-BHI and hemoline performance diphasique]. AB - The Liquoid-BHI, biphasic blood culture system, was compared with a conventional blood culture bottle (Hemoline performance diphasique) in 3125 paired blood cultures. Both systems were inoculated with equal volumes of blood (5 ml). Streptococcus spp. (P less than 0.02) and S. epidermidis (P less than 0.05) were recovered from BHI system. In contrast, P. fluorescens (P less than 0.02) were recovered in conventional system. No important differences were found for other bacteria and fungi. For optimal detection of microorganisms, however, the biphasic BHI system should be paired with conventional bottle. PMID- 3330243 TI - [Alloalbuminemia associated with myeloma]. AB - Alloalbuminemia occurring together with paraproteinemia in a case of proven myelomatosis is described. The clinical and laboratory findings of this case are listed. The importance of the reported case is emphasized. PMID- 3330244 TI - [Comparison of methods for the isolation of beta-hemolytic streptococci]. AB - Throat swabs from 334 patients, submitted to the clinical laboratory of the Institute of Infectious Diseases (Siena University), for isolation of beta hemolytic streptococci, were inoculated and incubated aerobically and anaerobically. Beta-hemolytic streptococci were identified in 117 (35%) cases, including 77 group A streptococci. Group A streptococci were recovered significantly more often with anaerobic incubation than with aerobic incubation (77 versus 53 cases: P less than 0.01). Non-group A beta-hemolytic streptococci also were recovered significantly more often with anaerobic incubation (40 versus 22; P less than 0.01). We conclude that anaerobic incubation for throat cultures is superior to incubation in normal air for detection of beta-hemolytic streptococci. PMID- 3330246 TI - [Current immunological diagnosis of collagenoses. I. Systemic lupus erythematosus and systemic scleroderma]. PMID- 3330245 TI - [In memory of the editor of "Przeglad Dermatologiczny", Dr. Krystyna Moskalewska]. PMID- 3330247 TI - [Treatment of dyskeratosis follicularis (Darier's disease) with aromatic retinoid]. PMID- 3330249 TI - [Pemphigus foliaceus preceded by pemphigoid in a patient with thymoma: coincidence or pathogenetic relationship?]. PMID- 3330248 TI - [Combined methods including PUVA therapy in the treatment of psoriasis]. PMID- 3330250 TI - [Evaluation of the clinical trial of the stimulation of uterine contraction by prostaglandin]. PMID- 3330251 TI - [Acute pancreatitis: current views on the pathophysiology and the methods of treatment]. PMID- 3330252 TI - [Evaluation of the effectiveness of gemfibrozil in primary dyslipoproteinemias. I. Changes in lipid levels after treatment (the "net" reduction)]. PMID- 3330254 TI - [A brief history of nephrology]. PMID- 3330253 TI - [Evaluation of the effectiveness of gemfibrozil in primary dyslipoproteinemias. II. Relation between the results of treatment and type of dyslipoproteinemia]. PMID- 3330255 TI - [Nephrotic syndrome]. PMID- 3330256 TI - [Urinary infection in childhood]. PMID- 3330258 TI - ["Reval" casting technic. 1]. PMID- 3330259 TI - ["Reval" casting technic. 2]. PMID- 3330257 TI - [Complete rehabilitation of the maxillary arch with a mixed prosthesis]. PMID- 3330260 TI - [Perio-preventive fabrication of a reconstruction with compression-stud attachments]. PMID- 3330261 TI - [Various factors which influence the precision of GC Vest G castings--flexible phosphate investments]. PMID- 3330262 TI - [Prevention of toxic risks in dental prosthetics]. PMID- 3330263 TI - Bracken carcinogenicity. PMID- 3330264 TI - Diet, ageing and cancer. PMID- 3330266 TI - [Functional dissociation of the kidney-adrenal axis in idiopathic hyperreninemic hypoaldosteronism]. PMID- 3330265 TI - Effects of caffeine on chromosomes in cells of higher eukaryotic organisms. PMID- 3330267 TI - [Ileocecal invagination in the adult caused by pedunculate lipoma of the terminal ileum. Description of a case and review of the literature]. PMID- 3330269 TI - [Histo-morphometry of the bone in metabolic diseases of the bones]. PMID- 3330268 TI - [Efficacy and tolerability of iron protein-succinyl versus ferritin in sideropenic anemia]. PMID- 3330270 TI - [Opioid peptides and the regulation of arterial pressure]. PMID- 3330272 TI - Present concepts in the treatment of neuroblastoma. AB - The outlook for the child with neuroblastoma remains dismal. The tumor has been known to undergo spontaneous resolution, and this phenomenon has led to increased interest and research in possible immune mechanisms that may be involved. Treatment often involves the use of surgery, radiation, and chemotherapy, frequently producing a short-term response, but a cure of the disease in an advanced stage can rarely be attributed to any of these treatment modalities. The present staging and treatment method used by the authors is that of the Pediatric Oncology Group (POG) #8104. As far as the immunological therapeutic approach is concerned, promising results have been obtained in animal studies with monoclonal antibodies and immunocellular components. Cumulative data from various pediatric centers have showed that the patient's age strongly influences the prognosis in all stages of the disease. PMID- 3330271 TI - [Secondary myxoid liposarcoma in a patient with Hodgkin's disease. Report of a case]. PMID- 3330273 TI - Advances in the treatment of rhabdomyosarcoma. AB - Rhabdomyosarcoma is the most common soft tissue sarcoma in children under 15 years of age. Several decades ago it was associated with an 80% mortality rate. Recent advances with combined modality therapy have improved the 5-year survival rate to almost 70%. The focus for the improvement in treatment regimens is now shifting to concerns regarding the preservation of body function and the treatment of far advanced disease. Regardless of age, histology, stage, or site of primary tumor, there has been no group where chemotherapy has not been proven beneficial. The current recommendations used by the Intergroup Rhabdomyosarcoma Study, with regard to chemotherapy, are summarized. Radiation therapy adjunctive to surgery has a useful place in the treatment of rhabdomyosarcoma, but prophylactic nodal irradiation is not recommended. Involved nodes should, however, be treated. Since the potentially adverse side effects of chemotherapy and radiation are accentuated when combined, radiation therapy is no longer recommended in patients with group I rhabdomyosarcoma. Prognostic factors and future considerations from the operative standpoint are presented. PMID- 3330274 TI - Malignant lymphomas in children and adolescents. AB - Malignant lymphomas constitute the third most common group of childhood cancers in the United States. Hodgkin's disease (HD) exhibits a bimodal age peak, with the first peak occurring in the 15-34-year age group. Nodular sclerosis is the most common histologic subtype of HD seen in children. The disease tends to be primarily supradiaphragmatic at presentation. Accurate staging is essential for determination of appropriate therapy. Staging laparotomy with splenectomy is indicated for those patients with clinically localized disease whose therapy may be altered by pathologic staging. Radiation therapy is curative in the great majority of patients with localized disease. Multimodality therapy has been employed with increasing success in patients with advanced disease. The late sequelae of therapy must be considered in the design of optimum therapeutic regimens. More than 90% of non-Hodgkin's lymphoma (NHL) in childhood can be grouped into one of three histologic subtypes: lymphoblastic, undifferentiated, and diffuse large cell type. Lymphoblastic lymphomas most commonly present with mediastinal involvement. The majority of nonlymphoblastic lymphomas arise within the abdomen. Because of the tendency of NHL for extralymphatic dissemination, systemic therapy is always required. Treatment is determined by stage and histology. Significant improvements in survival rates have resulted from the development of effective combination chemotherapy programs. Cure rates in excess of 90% can be expected in children with localized disease. The outlook for children with advanced disease of undifferentiated histology remains poor. The presence of central nervous system involvement at diagnosis is a particularly ominous sign. PMID- 3330275 TI - Testicular tumors in infants and children. AB - Primary malignant tumors of the testis are uncommon in infants and children. Tumors of germ cell origin are identified most frequently. The clinical presentation is usually due to the presence of an enlarging scrotal mass. Determinations of the serum alpha fetoprotein (AFP) and beta subunit of human chorionic gonadotropin (beta-hCG) levels are helpful for diagnosis and management. All suspected testicular tumors should be surgically evaluated through a high inguinal incision. Postoperative chemotherapy is recommended for some patients with yolk sac tumor and all patients with embryonal rhabdomyosarcoma. Prolonged relapse-free survival is possible for most infants and children with malignant testicular tumors. PMID- 3330276 TI - Neoadjuvant chemotherapy and surgery of cancer of the esophagus. AB - Neoadjuvant, or preoperative, chemotherapy for esophageal cancer has become an area of increasing interest because of the failure of conventional therapy (surgery or radiation) to improve disease-free or overall survival. Several autopsy series have demonstrated that, in many symptomatic western patients, esophageal cancer is a systemic disease. Neoadjuvant chemotherapy thus, in theory, allows a simultaneous attack on both the primary and metastatic disease. A number of single-arm, phase II multimodality trials have been completed. Toxicities of chemotherapy, while substantial, have been tolerable. With careful attention to detail, operative morbidity and mortality has not been increased. Large-scale randomized trials are needed to evaluate the impact of this technique on disease-free and overall survival. PMID- 3330277 TI - Oral manifestations of systemic chemotherapy and their management. AB - Many antineoplastic drugs in use now have cytotoxic side effects that also manifest in the oral cavity or influence dental management. Chemotherapeutic agents that have a high potential for precipitating oral mucosal damage and bone marrow depression are methotrexate, cyclophosphamide, daunorubicin, doxorubicin hydrochloride, 5-fluorouracil, bleomycin, nitrogen mustard, cytosine-arabinoside, 6-mercaptopurine, busulfan, and L-phenylalanine mustard. Mucositis may lead to neglected oral hygiene, which in turn may cause a chain reaction of local infections, bleeding, and septicemia in myelosuppressed patients. Preventive oral care before chemotherapy and active oral care during therapy are necessary for compromised patients. A protocol for oral care is described. PMID- 3330278 TI - The current status of early detection and screening for colorectal cancer. AB - There are several approaches to the early detection of colorectal cancer that currently are in use in various segments of the health care system. Herein, the status of cancer control research regarding symptom and risk factor assessment, sigmoidoscopy and colonoscopy, double contrast barium enema, and fecal occult blood testing is reviewed. In addition to the different technologies of early cancer detection, there are different models of disease control intervention. These include the routine clinical activities of primary care providers as well as programmatic screening of mass populations. The currently available techniques for early colorectal cancer detection appear better suited for existing patient care settings than for programs outside the direct supervision and follow-up of the health professional. PMID- 3330279 TI - Radiation-induced chronic arterial injury. AB - Acute arterial disruption associated with infection, previous irradiation, and the postoperative state is a well-described entity. The recognition of a chronic form of radiation-induced arterial injury presenting years after therapeutic doses of radiation is less well appreciated. This paper summarizes the vital data obtained by reviewing the literature concerning 162 cases of arterial injury associated with prior radiotherapy. The vessels involved include coronary arteries, the aorta, renal arteries, the extra- and intracranial circulation, the ilio-femoral system, and the upper extremity arteries. A review of the histologic findings, the studies regarding pathogenesis, and the morphology of the lesions found in these 162 patients suggests a disease distinct from the atherosclerotic process. PMID- 3330280 TI - [Scanning electron microscopy study of the structure of enamel prepared for bonded anchorages]. PMID- 3330281 TI - [The stomatology of Bossuet (1627-1704) and that of Winslow (1669-1760)]. PMID- 3330282 TI - Management of furcation involvement. PMID- 3330283 TI - [How to integrate initial treatment in periodontics into daily practice]. PMID- 3330285 TI - [Circulation of blood, that of which one does not speak: Ibn Al Nafis 1210-1288]. PMID- 3330284 TI - [Significance of a hemostatic treatment with a base of collagen in oral medicine]. PMID- 3330286 TI - [Dentin bonding: strategies according to tissue status]. PMID- 3330287 TI - [Activation of prefabricated precision attachments. Reality or illusion?]. PMID- 3330288 TI - [All the light on transparent wedges]. PMID- 3330290 TI - [Functional modelling of polished surfaces of the maxillary removable complete dentures]. PMID- 3330289 TI - [Georges Cuvier (1769-1832). Biology and the teeth]. PMID- 3330291 TI - [Peptic ulcer: a medical point of view]. PMID- 3330293 TI - International course on "Immunological Techniques in Paediatric Rheumatology". International Symposium on "Juvenile Arthritis". Proceedings. Pavia, Italy, 5-11 October 1986. PMID- 3330292 TI - [Peptic ulcer: a surgical point of view]. PMID- 3330294 TI - Immunological abnormalities in juvenile chronic arthritis. AB - The immunological alterations that have been reported in juvenile chronic arthritis are reviewed. Their role in patient management and classification as well as their possible etiopathogenetic relevance are discussed. PMID- 3330295 TI - Seronegative arthritis--etiology and diagnosis. AB - Seronegative arthritis is part of a multifactorial syndrome which also includes acute anterior uveitis (AAU), psoriasis, inflammatory bowel disease and forms of A-V block and aortic incompetence. The whole syndrome may be referred to as HEreditary Multifocal Relapsing Inflammation (HEMRI). Any sign may occur alone or in combinations with others. The signs may be triggered by infections, the arthritic components are then referred to as reactive arthritis. Genetic factors predetermine who is to contract disease when triggered. HLA-B27 itself is probably of major significance in ankylosing spondylitis and AAU. A genetic factor in linkage disequilibrium with HLA B13 and B17 is instrumental in familial psoriasis. Other genetic factors may determine psoriatic arthritis, and possibly also inflammatory bowel disease and juvenile arthritis. The genetic factors interact with each other and with the environmental factors when producing disease. Diagnosis should be based on demonstrated signs of disease. Classification according to genetic factors reflects etiology, disease manifestations and prognosis. PMID- 3330296 TI - Prospects in the immunological treatments of rheumatoid arthritis. AB - Different trends in the therapeutic immunomodulation of rheumatoid arthritis (RA) have been developed since a few years. Early treatment and/or combined treatments using 2 or 3 classical remission inducing drugs could improve the clinical results. Diet and especially eicosapentanoic acid could influence the clinical signs of RA. Among the non specific immunodepressive agents, methotrexate is of major interest. Immunodepressive agents partly selective of a lymphocyte subpopulation: cyclosporin A, total lymphoid irradiation, act on CD4 cells. Some experimental immunomodulating drugs are under study: type II interferon, thymic hormones, immunoglobulins of placental origin. The specific immunotherapy of RA is still experimental and only used in animal with very promising results. Anticlass II HLA monoclonal or polyclonal antibodies could be one of the major treatments of autoimmune diseases within a few years. The treatment of RA by anti idiotype antibodies remains, at this moment, theoretical. PMID- 3330298 TI - [60th anniversary of the publication of Acta Physiologica Sinica]. PMID- 3330297 TI - Infection and arthritis. AB - The categorization in four classes of association between infection and arthritis (namely infective, post-infective, reactive and idiopathic) seems nowadays to be inadequate to cover the extensive field of interactions between infectious agents and host response resulting in arthritis. This paper is a synthetic review of the subject with particular reference to pathogenetic mechanisms in children. An effort has been accomplished, on the basis of the most recent literature, to define the respective roles of the microbial aggression and the host response in a number of conditions: septic arthritis, viral arthritides, Lyme arthritis, rheumatic fever, Reiter's syndrome, ankylosing spondylitis and rheumatoid arthritis. PMID- 3330299 TI - Household influences on childhood mortality: evidence from historical and recent mortality trends. PMID- 3330300 TI - [Renal colic: symptoms manifesting an aorto-iliac aneurysm. Clinical case]. PMID- 3330302 TI - [Modification of the Pereyra technic in female stress incontinence using fragments of autologous tissue]. PMID- 3330301 TI - [Piperacillin in the treatment of chronic bacterial prostatitis]. PMID- 3330303 TI - [Adenomatoid tumors of the epididymis. Observations on 3 cases]. PMID- 3330304 TI - Donor ambivalence: a key issue in families of children with end-stage renal disease. AB - This paper is based on the writers' clinical experience with children and adolescents who receive kidney transplants and members of their families who are involved in the process of identifying the best donor match. Specific concerns of the patients and their significant others are described, and two cases are used as illustrations. The role of ambivalence in donor selection is investigated and selected intervention sites are suggested. PMID- 3330305 TI - Liver transplantation in the adult. PMID- 3330306 TI - Renal transplantation in children. PMID- 3330307 TI - Aspiration cytology in organ transplantation. PMID- 3330308 TI - Hepatitis in renal transplant recipients. PMID- 3330309 TI - Cyclosporine conversion. PMID- 3330311 TI - Accelerated coronary arteriosclerosis in cardiac transplant recipients. PMID- 3330310 TI - Use of living donors in renal transplantation. PMID- 3330312 TI - Genitourinary complications in renal transplantation. AB - The surgical aspects of renal transplantation have now been studied thoroughly. Yet, technical complications are still common. This review may seem too complex, but proper attention to many small details means the difference between success and failure, or at least between large and small morbidity. Reduction of genitourinary complications is due to many innovations. The external ureteroneocystostomy is a primary method of urinary reconstruction which is simpler and produces fewer complications than the alternative procedures. Further, the complications that do occur are more easily and promptly treated. The end-to-side ureteroureterostomy, as currently performed, provides a ready secondary method of reconstruction if the primary method fails. The early exploration and operative correction of genitourinary complications substantially reduces long-term morbidity and mortality. PMID- 3330313 TI - Use of cyclosporine in transplantation of nonprimarily vascularized tissues. PMID- 3330314 TI - [Current aspects of the use of metronidazole in periodontal disease]. PMID- 3330316 TI - [Statistical analysis of (completely or partially) edentulous patients covered by social health insurance (2460 cases)]. PMID- 3330315 TI - [Occupational hearing loss in relation to dentistry]. PMID- 3330317 TI - [Current methods of diagnosis of parotid tumors. Radionuclide imaging and gray scale ultrasonography]. PMID- 3330319 TI - [Prosthodontic-periodontics relations. B. The margins and design of fixed dentures]. PMID- 3330318 TI - [Periodontal treatment of patients with periodontal-prosthetic problems]. PMID- 3330320 TI - [Current concepts of cervical fractures of the teeth and their treatment]. PMID- 3330321 TI - Penetrating keratoplasty for the treatment of pseudophakic corneal edema associated with posterior-chamber lens implantation. PMID- 3330323 TI - [Causes of death in patients treated with cimetidine--a phase 4 study]. PMID- 3330324 TI - [Culture of the expectorate in respiratory tract infections. Is it worth the trouble and expense?]. PMID- 3330325 TI - [Diagnosis of vaginitis in general practice]. PMID- 3330322 TI - Squamous cell carcinoma of the submandibular gland. PMID- 3330326 TI - [Total intravenous anesthesia with phentanyl-diazepam-etomidate. A controlled study]. PMID- 3330327 TI - [Calcium intake and hypertension]. PMID- 3330328 TI - [Regret after female sterilization. Review of the literature with a description of groups at risk]. PMID- 3330329 TI - [Long-term treatment using oxygen in chronic obstructive lung disease]. PMID- 3330330 TI - [Compartment syndrome with streptococcal septicemia]. PMID- 3330331 TI - [Allergic bronchopulmonary aspergillosis]. PMID- 3330332 TI - [A rapid method for theophylline determination in whole blood]. PMID- 3330333 TI - [Gallbladder stone diagnosed with ultrasound]. PMID- 3330334 TI - [Tissue pressure in the pancreas measured with ultrasonic-guided puncture]. PMID- 3330335 TI - [Secretory otitis media. IV. Medical consensus conference in Denmark]. PMID- 3330336 TI - Clinical sound speed measurement in liver and spleen in vivo. AB - The paper describes an implementation of clinical sound speed measurement using either a commercial water path scanner or a specially developed dual transducer real time scanner, each interfaced to a general purpose minicomputer for off-line analysis. It describes the examination technique to obtain suitable in vivo clinical data from the liver and the spleen. It develops signal processing methods to achieve clinical confidence in individual measurements. Forty-five liver patients and 46 spleen patients were examined. Sound speed was found to correlate closely with fibrosis content in both the liver and the spleen with an increase in fibrosis resulting in a decrease in sound speed. Sound speed in various pathological conditions are discussed. Clinical results of sequential examinations on patients under treatment are presented and successful monitoring of the disease status is demonstrated. The potential clinical role of sound speed measurement is suggested. PMID- 3330337 TI - Evaluation of ultrasonic attenuation in diffuse diseases of spleen and liver. AB - Ultrasonic attenuation has been measured using frequency domain signal processing in clinical trials of patients with liver and spleen diseases. By comparing the variance encountered in local measurements and in measurements at a number of adjoining sites, the need for averaging over large volumes of tissue to avoid the effects of large fluctuations is established. In spleens of patients with myelofibrosis, no correlation between fibrosis and attenuation was found. However it was found that variations in splenic volume were accompanied by inverse changes in attenuation, most likely due to blood pooling. A correlation was found between splenic blood flow per unit organ volume and attenuation. In cirrhotic livers, attenuation was significantly increased with fatty infiltration, but only slightly increased in livers containing minimal fat. These findings tend to reduce the probability of finding successful clinical applications for attenuation slope measurements. PMID- 3330338 TI - Diffraction correction for focused transducers in attenuation measurements in vivo. AB - Diffraction effects are a cause of error when estimating the frequency dependent attenuation of ultrasound in biological tissues in the reflection mode. Comparison of attenuation values estimated in vivo by different investigators using different types of transducers makes calibration and correction for diffraction necessary. In this paper, we present experimental results for in vivo calibration and correction for the diffraction effect for focused transducers. We also study numerically the diffraction filter in a time-frequency representation, and show that for a focused probe, there is a region in the time-frequency domain where the frequency slope of the diffraction filter does not vary with time. The main consequence for in vivo estimation is that for a given probe, it is possible to select both the distance between the region of interest and the probe, and the frequency limits, such that the attenuation thus estimated is unbiased by the diffraction effect. This result, obtained by numerical calculations, is confirmed by experimental calibration of a foam phantom and in vivo muscle. PMID- 3330339 TI - An improved ultrasound simulation model: use in evaluating log versus linear processing for lesion detection. AB - This paper reports the development of an improved three-dimensional computer simulation model for evaluation of ultrasonic imaging systems. This model was used to successfully evaluate a signal processing method for improving lesion detection in ultrasound imaging. Linear processing of the rf signal amplitudes from a limited region of tissue was compared with the logarithmic compression employed by most commercial scanners. Two lesions were simulated by spherical distributions of scatterers having backscatter coefficients greater than the scatterers in the surrounding medium. Linear processing improved the differential contrast by a factor of about two. The simulation is based on the three dimensional distribution of acoustic frequency spectra in a transducer beam and integration of scattered pulses from a corresponding three-dimensional array of scatterers. The simulation reported in previous papers depended upon physical measurement of the impulse response of a transducer. An original contribution described briefly herein, and in more detail in a companion article, is the addition of a model of the transducer's pulse waveform generation. Another new addition is the definition of a specific lesion detection task for objective assessment of a change in image quality following perturbation of some system parameter. PMID- 3330340 TI - Digital simulation of pulsed ultrasonic waveforms. AB - When modeling or simulating an ultrasonic pulse-echo system it is necessary to know the transducer waveforms that are the input to the system. In general, accurate transducer modeling is complex and waveform calculation is computationally intensive. Because of this, investigators often assume these waveforms to be simple sinusoids, modulated by Gaussian or exponential envelopes. However, these latter type pulses do not properly represent the complex response of modern piezoelectric transducers. In this paper, a simple set of equations is presented which can approximate the behavior of a number of common transducer configurations. In the first step of the procedure, a simple but accurate model is employed to calculate the step responses of quarter-wave-matched and backed piezoelectric transducers, assuming open circuit conditions. Effects of electrical terminations and transmit/receive bandwidth limitations are accounted for, approximately, by cascaded filtering. Emitted pressure waveforms and echo voltage waveforms synthesized by this simple procedure are very similar to measured waveforms from real transducers. Under most conditions, the method is only an approximation because the model erroneously assumes isolation between the electrical and acoustic networks. However, under many conditions the model is sufficiently accurate to predict actual transducer performance. PMID- 3330341 TI - [Methods for the surgical treatment of postburn contractures of the shoulder joint]. AB - Based on their experience with the treatment of 93 patients with postburn adduction contracture of the shoulder the authors propose a classification related with localization of scars. Marginal contractures are successfully treated by plasty with a trapezoid skin-fat flap from the axillary cavity with/without a combination with the displacement of scarry tissues or free skin plasty; the medial contracture--by one or several pairs of trapezoid skin-fat flaps cut from leaves on the sides of the scar fold; the total contracture with the absence of intact skin in adjacent fields can be adequately eliminated by mobilization a quadrangular island in projection of the dropped axillary cavity to the normal level of the cupola, fixation of narrow sides to the wound margins on the anterior and posterior surface of the humeral articulation and closure of wounds on the shoulder and chest with the splitted skin; the anterior-posterior contracture is eliminated either in the same way as the marginal one, or by cutting a quadrangular flap in the center of the axillary cavity as in the total contracture. PMID- 3330342 TI - [Wounds and contusions of the heart]. PMID- 3330343 TI - [Formation of the bronchial stump in pulmonectomy]. AB - An analysis of different incidence of the development of the bronchus stump incompetence after right and left pulmonectomies (228 observations) has shown that the width of the membranous part and the form of the transverse cross section of the main bronchus might influence the reliability of the stump created in suturing by approximating stitches. A method of strengthening the posterior wall of the bronchus stump has been developed by means of suturing the bronchus wall in the lateral direction so that the longitudinal axis of the stump be oriented in the sagittal plane. The method was used in 39 pulmonectomies. The punctate incompetence of the bronchus stump made its appearance in 3 patients. PMID- 3330344 TI - [The Vestnik Khirurgii during the years of Soviet power]. PMID- 3330345 TI - [Effect of a drainage operation on gastric secretion in patients with duodenal ulcer after vagotomy]. AB - The work analyzes alterations of gastric secretion in 687 patients subjected to various kinds of vagotomy in combination with or without draining operations on the stomach for ulcer of the duodenum. Draining operations were established to decrease activity of gastric secretion. The Jaboulay gastroduodenal anastomosis proved to be less beneficial since 50% of the patients had the positive insulin test and ulcer recurred almost in 11% of the cases. Results were most favorable after vagotomy in combination with pyloroplasty after Finney and Heineke Mikulicz. The disease recurred after these interventions in 7 and 8% correspondingly. PMID- 3330346 TI - [Gastric resection with preservation of the pyloric sphincter in treating patients with duodenal ulcer]. AB - An experience with pylorus-preserving resections of the stomach in 27 patients with duodenal ulcer and very high acid production is described. Specific technical features of this operation, immediate and long-term results are analyzed. Rhythmic evacuation was preserved in addition to a reliable drop of the acid production. Gastroduodenal reflux was prevented. Positive results were noted in all the examined patients in the remote follow-up. PMID- 3330347 TI - [Intervention on the portal vein in pancreatic resection]. AB - The authors consider that resection of the pancreas with the intervention portal vein must be fulfilled by a specially trained team of surgeons--masters technique of operations on the vessels. The operative method should be chosen dually and depends on the localization and size of the vessel injury. PMID- 3330348 TI - [Importance of ultrasonic echolocation in the differential diagnosis and observation of the development of pancreatic pseudocysts]. AB - Under observation there were 84 patients with pseudocysts of the pancreas, in 12 of them the main diagnostic method was ultrasonic echolocation. The differential diagnosis between the cyst and tumor was sometimes difficult. The most characteristic sign of the disintegrating tumor was a considerable and irregular thickening of the wall of the cavitary formation found. In four cases repeated ultrasonic examinations in dynamics made it possible to register the involution of pseudocysts which took place within 3-4 weeks after the onset of the disease. PMID- 3330349 TI - [Diagnosis and treatment of adrenal cysts]. AB - The authors have analyzed literature data of 303 cases of adrenal cysts and describe their two cases (both patients were operated on with good results). Problems of diagnosis and treatment of this rare disease are discussed. PMID- 3330350 TI - [A shunting method in the aortoiliac segment]. AB - Results of various kinds of reconstructive interventions in 237 patients with atherosclerotic occlusions of the abdominal aorta and iliac arteries are described. Shunting operations and prostheses in the aortoiliac segment in 76% of the patients give prolonged and considerable improvement of blood circulation in lower extremities. The most favorable results were obtained in patients who had been subjected to reconstructive operations on the aortoiliac segment with transprosthesis aortotomy not requiring an exclusion of the aorta and iliac arteries from blood circulation. There were no severe complications and lethal outcomes in this group of patients. The amount of thromboses decreased markedly, intestinal pareses were less frequent, the volume of blood transfusions became less and operations shorter. PMID- 3330352 TI - [Active surgical treatment of local suppurative diseases in patients with diabetes mellitus]. PMID- 3330351 TI - [Surgery of extrapulmonary tuberculosis during the 70 years of Soviet power]. PMID- 3330353 TI - [Surgical treatment of non-gunshot wounds of the soft tissues of the face and neck]. AB - The primary surgical treatment of injured soft tissues of the maxillofacial area is performed with special reference to anatomo-physiological features of the injured area, mechanism and character of the trauma. Complete closure of all wound surfaces is a necessary condition of the primary surgical treatment of wounds of the face with elements of primary plasty when necessary. It gives the best functional and esthetic results and a more valuable preparation of the injured area for the following reconstructive operations. PMID- 3330355 TI - Organophosphorus compounds. II. Metabolic considerations. AB - Organophosphorus compounds are esters of alcohols with phosphoric acids or anhydrides of phosphoric acids with some other acids. The most important groups are the phosphates, phosphorothionates, phosphorothioates, phosphoroamidates, phosphorochloridate and phosphonates. The metabolism of phosphorothionates and phosphorothioates involves initial activation (oxidative desulphuration) followed by hydrolysis of the active metabolites. Activation is carried out by the action of microsomal oxidases, and degradation is performed by different types of hepatic and plasma esterases. PMID- 3330354 TI - Comparative pathology of canine hereditary nephropathies: an interpretive review. AB - Hereditary nephropathies in dogs represent multiple complex clinicopathological entities which cause renal failure in juvenile, adolescent, and young adult dogs. To date, nephropathies believed to have a genetic basis have been described in 11 breeds. These disorders represent a variety of developmental, degenerative, and metabolic defects. Many canine hereditary nephropathies are analogous to childhood nephropathies in man. Review of the veterinary literature, comparative pathology, and avenues of future research are discussed. PMID- 3330357 TI - [The antipyrine test: its 35-year history and prospects]. PMID- 3330356 TI - [Obesity and hypertension]. PMID- 3330358 TI - [The origin of intrauterine contraception]. PMID- 3330359 TI - [History of the surgical treatment of pulmonary tuberculosis]. PMID- 3330360 TI - [Proteolytic enzymes and their natural inhibitors in patients with bronchiectasis]. PMID- 3330361 TI - [Effect of antiepileptic drugs on thyroid function]. PMID- 3330363 TI - [History of Cicero's illness]. PMID- 3330362 TI - [Psychiatric complications during the treatment with disulfiram]. PMID- 3330366 TI - [Various determinants of the course outcome of schizophrenia]. PMID- 3330365 TI - [The biological role of lysozyme and its usefulness in clinical practice]. PMID- 3330364 TI - [Development of present-day cardiological science in Poland at the turn of the 19th century]. PMID- 3330367 TI - [Sociological evaluation of suicide and attempted suicide]. PMID- 3330368 TI - [75th anniversary of the Polish Committee of Sanitary Service]. PMID- 3330370 TI - [Contraception with steroids in the male. Experimental basis]. AB - Inhibition of spermatogenesis is possible with many types of steroid hormones. Theoretically they could be used alone or in combination for male fertility control. PROBLEMS: Oral active androgens or anabolic steroids when given in doses needed to inhibit spermatogenesis are liver toxic. Injections or administration of depot preparations every 14 days or 4 weeks is not practicable. Azoospermia or oligozoospermia does not occur immediately and examination of the ejaculate would be necessary to be sure whether and when azoospermia is achieved. Patients with oligozoospermia are not always infertile. It is known from animal experiments and from prostatic carcinoma patients that after long term suppression of pituitary function by treatment with steroid hormones the hypothalamic pituitary system becomes adapted to the high hormone levels and starts to secret gonadotrophins again. Consequently spermatogenesis is no longer fully inhibited. Regular controls of the ejaculate would be necessary to be sure, that azoospermia still persists. Spermatogenesis is also inhibited by synthetic progestogens. As compared with the doses in oral contraceptives, the doses needed for inhibition of spermatogenesis are at least 10x higher. When given alone there is also a loss of libido and potency which demands additional substitution with androgens. Concerning antiandrogens it will not be possible to find a dose for men which is reliably antifertile but which does not affect other androgen-dependent functions including libido. GnRH-agonists and antagonists have to be combined with an androgen. But there are some other still unsolved problems. IN CONCLUSION: A method for fertility control in men based on steroid hormones will not be realized in the next future. PMID- 3330369 TI - [Risk-benefit analysis of contraception with steroids]. AB - Oral hormonal contraception is a low risk and safe form of contraception for women between 15 and 35 years of age without risk factors in the history (smoking, obesity, diabetes mellitus, hypertension, hypercholesterinemia). Women over 35 years should take the pill only when risk factors have been excluded previously. In general, low dose pills with less than 50 micrograms ethinylestradiol should be used, because they have the lowest impact on the metabolism. There should be an additional indication even after exclusion of risk factors, if women over 40 years take the pill. Besides that it could be shown that using the pill has many positive effects on health, as for example benign mamma tumors more seldomly occur, in most of the cases the dysmenorrhoea improves, anaemia and inflammatory adnex diseases are significantly more seldom, and it could be shown that there is a clearly protective effect concerning the morbidity of endometrium and ovarian cancer. PMID- 3330371 TI - [Contraception with steroids in the male. Clinical possibilities]. AB - Spermatogenesis is predominantly regulated by pituitary gonadotropins. LH influences gamete production via stimulation of Leydig cells, resulting in high intratesticular testosterone concentrations, while FSH exerts its effects on Sertoli cells. Theoretically azoospermia can be achieved by suppression of gonadotropins, whereby, however, a severe decrease in androgen production would also occur. Since testosterone is required for normal male sexual function, maintenance of secondary sex characteristics, bone and protein metabolism as well as for gender identity, androgens must be an integral part of any male contraceptive method acting via suppression of gonadotropins. Although testosterone esters alone (testosterone-propionate, oenanthate, or cypionate) lead to azoospermia in a certain proportion of men, effectiveness is increased when they are combined with other antigonadotropic substances such as gestagens. Among different combinations tested testosterone oenanthate and depot medroxy progesterone acetate were used most frequently. Instead of gestagens other steroids such as danazol and cyproterone acetate have been tested but azoospermia, the final goal of these investigations, has never been achieved in all participants. Results from non-human primates indicate that substitution with available testosterone esters may by itself maintain spermatogenesis due to high serum levels after injection. Better results with 19-nortestosterone-hexyl oxyphenyl-propionate seem to support this hypothesis. In the future, it is likely that testosterone ester with smooth pharmacokinetic profiles or microencapsulated testosterone in combination with gestagens or with GnRH analogues will lead to a male contraceptive method based on endocrine means. PMID- 3330372 TI - [Working mothers and their significance for the children from the viewpoint of clinical psychology]. AB - The possible effects of maternal employment on children were investigated. Whereas 30 years ago especially behavior disorders were found to be correlating, today the situation is more differentiate. Results suggest, that the effects of maternal employment have changed the years. The effects depend on the degree of the mother's satisfaction with her work, the sex of the children, social class, children's age, residential area, substitute care, the possibility to conciliate working and private needs as well as the attitude of society regarding working mothers. The part of the father in this connection is controversial. Lately unconscious motives of working (e.g. career drive resulting from early familial conflicts, marriage problems) or non-working (e.g. fear of occupational conflicts) mothers are regarded more intensively. Correlations are especially found to sex role understanding of the children, as well as to intelectual development and emotional stability dependent on further factors. PMID- 3330373 TI - [A retrospective on behaviorism]. AB - This essay regards the behaviorism as a component of the industrial civilization and the formation of science according to it. The power of the objectivistic "Aussenweg" (Husserl) and man's exteriorization are discovered in Skinner's analysis of human behaviour, in the thought of a psychologist who denies human freedom and follows a perspective of external controls. The behaviorism, the instrumentalization of men and of the human reason are connected with the philosophy of Descartes and Carnap. Finally the deficient truth of the behaviorism becomes distinct in the thoughts of a phenomenological "Selbstvertiefung" and a creative "Phanopraxie". PMID- 3330374 TI - ["Restoring health mechanically"--Gustaf Jonas Wilhelm Zander's treatment principles]. PMID- 3330375 TI - [The sonographic assessment of femoral neck anteversion]. PMID- 3330376 TI - [A computer-assisted electromechanical measuring system for the study of flexion and extension forces in the upper ankle joint]. PMID- 3330377 TI - [Periodontopathies, toothpastes and sodium lauryl sulfate]. PMID- 3330378 TI - [Dental diseases are already thousands of years old]. PMID- 3330379 TI - [Cerec-System: computerized inlays, onlays and shell veneers]. PMID- 3330380 TI - [New technology for the construction of fixed partial dentures]. PMID- 3330381 TI - [Spark erosion fit correction of cast objects, in particular partial crowns]. PMID- 3330382 TI - [Complete and glass-ceramic crowns clinically considered]. PMID- 3330383 TI - [Tooth extraction required as a pledge of love]. PMID- 3330384 TI - [The slow progress of periodontology toward modern standards]. PMID- 3330385 TI - [Renal transplantation and Bourneville's tuberous sclerosis]. AB - A kidney transplantation was performed in July 1981 on a 29 year old woman who presented the signs of tuberous sclerosis and suffered from chronic renal failure. The frequency and the genetic transmission of Bourneville's disease are explained. The signs of the disease are exposed with special emphasis on the renal lesions. Only the patients with minor neurological symptoms can survive. These patients are able to develop chronic renal failure. This occurs either when the kidneys are destructed by renal cysts or tumors, or when a bilateral nephrectomy must be performed for bleeding or tumoral compression. A kidney transplantation can give them an opportunity to live almost normally. When nephrectomy is not performed, a regularly follow-up is necessary because the unknown future of the renal lesions in place. PMID- 3330386 TI - Race, zygosity, and mortality among twins: interaction of myth and method. AB - For epidemiological purposes, it is customary to assume that same-sex (SS) dizygotic (DZ) twin pairs are approximately equal in number to unlike-sex (OS) DZs, the remainder of the SS pairs being monozygotic (MZ). It is also customary to consider OS-DZs to be epidemiologically representative of all DZs, which can only mean that difference in frequency of any trait between OS and SS twins is due to the MZ fraction of the SS twins. Since this is assumed as a premise, there is little value in its usual appearance as the result. The basic tenet of twin biology, that most twin excess anomalies are due to MZs, is a myth self perpetuated by a methodological tautology, and is false, at least for mortality. In a consecutively ascertained and prospectively studied sample of 616 twin pairs, over 80% diagnosed for zygosity, it can be shown that the standard assumption mentioned above have given impossible answers. The most probable possible answer is that mortality does not differ greatly with zygosity overall, but that SSDZ mortality is much higher than that of OS twins, and probably even higher than that of MZs. Race differences in the probable answers further suggest that standard assumptions of the Weinberg method may have consistently provided false explanations for race differences in the OS fraction of twin pairs. PMID- 3330387 TI - Toward a theory of human multiple birthing: sociobiology and r/K reproductive strategies. AB - Using symbols from population biology, a continuum of reproductive strategies can be distinguished ranging from r, the production of large numbers of offspring provided with minimal care, to K, the production of few offspring nurtured intensively. While all humans are at the K end of the continuum, some are proposed to be more so than others. If multiple egg production is part of an r reproductive strategy, certain facts may be ordered. Compared to mothers of singletons, for example, mothers of DZ twins have a lower age of menarche, a shorter menstrual cycle, a higher number of marriages, a higher rate of coitus, more illegitimate children, a closer spacing of births, a greater fecundity, more wasted pregnancies, a larger family, an earlier menopause, and an earlier mortality. Further, all twins have a shorter gestation period, a lower birth weight, and a greater incidence of infant mortality, with DZ twins having a greater frequency of health disorders, a higher mortality rate, and a lower rate of enrollment in volunteer registries. Multiple birthing also occurs more frequently in families of lower than of higher social status, and in those of African than of European and especially than of Oriental descent. PMID- 3330388 TI - Excessive twinning in a rural American genealogy: the demographic pedigree. AB - Excessive twinning in an extended family of rural Missouri concentrates in the isolated generations of 1874-1930s. Moderate inbreeding, larger sibships to older mothers, and access to local doctors may have combined to enhance this familial twinning. These biosocial factors are similar to an isolated case of excessive twinning in Scotland. PMID- 3330389 TI - Twinning in New England in the 17th-19th centuries. AB - Vital records of Saybrook and Plymouth in New England from the 17th century were investigated. Among 8,562 maternities 81 twin maternities were found, the twinning rate being 0.95%. Twinning rate was low at the 1st and 2nd births as compared with the 3rd or later births, and was highest at the 7th and 8th births (1.6%). Twin maternity seemed to be a strong risk factor to terminate reproduction, particularly after 6 or more children had been delivered. The rate of mothers who had any other child ("fertile" mothers) at the 7th or later birth order was significantly lower for twin (13%) than for singleton maternities (63%). Twinning rate also varied by the size of offspring of a mother, and those mothers who had 5 or 6 children showed the highest twinning rate (1.3%). Those fertile mothers who had 7 or more children showed the lowest twinning rate (0.74%), although an exceptionally higher twinning rate was seen at their last births. Elongation of the last birth interval was observed for each group of every family size, and higher twinning rates were generally observed at their last births. Reduction in fecundity and rise in twinning rate seem to have occurred simultaneously at the last stage of the reproductive period of mothers, regardless of their family size. PMID- 3330390 TI - Incidence of twinning in London from 1581 to 1760. AB - Baptism records of parishes in London and its vicinities from 1581 to 1760 (168,238 maternities) were investigated to estimate the twinning rate and its secular and seasonal variations. Total, estimated dizygotic (DZ), and estimated monozygotic (MZ) twinning rates were 1.1%, 0.8% and 0.3%, respectively. MZ twinning rate varied during the 18 decades, with a significantly low rate (0.11%) in the early 17th century (1621-1640). Significant seasonal variations of the twinning rate according to the month of baptism was observed in both DZ and MZ twins. DZ twins were born more frequently in spring and fall in general. Parish records obtained from four parishes near Manchester in England showed an inversed seasonal variation with peaks in winter and summer. An interpretation of this difference was discussed in a context of environmental factors. In the low MZ period, 1621-1640, MZ or like-sexed twins were apparently less frequent in summer (April to October). This result could be explained by a decrease of MZ twins and/or a greater loss of like-sexed DZ twins. PMID- 3330391 TI - Alternate changes in birth seasonality of twins during 1971-1984 in Japan. AB - Birth dates of 1,536 twin-pairs in 1971-1984 were collected from the members of an association of twins' mothers. The seasonal variation of twinning changed every 2-4 years. Years when twinning rate was higher in the summer-fall season (1971-72, 1976-77, 1982-84) and those when a peak of the rate was not observed (1973-75, 1978-81) appeared alternately. In years with a summer-fall peak, the elevation of twinning in the summer-fall season was detected consistently in both like- and unlike-sexed and in both MZ and DZ twin groups. The twinning seasonality in these years, however, was not evident in twin births of mothers who were born in May-July. These results suggest the possibility that seasonal factors which influence the twinning rate be not multiple-ovulation-inducing but probably abortion-inducing factors and most likely seasonally epidemic microbes. PMID- 3330392 TI - Cyclic variations of twin births at Isle-aux-Coudres: a case/control approach. AB - Twins and singletons were matched for several confounding factors. The monthly distribution of twin births and that of singleton births were compared with a uniform allocation of births over the year. Opposite seasonal variations emerged that were confirmed by a case/control comparison. Twins occurred more often in winter and early spring while singletons proved to be relatively few; singleton peaked in the fall season when the risk of a twin birth was low. These trends held across maternal age at birth and the time period of birth. Results suggest that the conception of a twin pair is highest in spring and early summer and lowest in winter. The role of sunlight in the twinning liability is discussed along with the role of sexual intercourse. That twin-prone mothers are usually more fecund in spring and early summer is a distinct possibility. PMID- 3330393 TI - The organization of the oocyte and embryogenesis in twinning and fusion malformations. AB - Certain congenital malformations occur in excess among twins and also among first degree relatives of twins. In the general population, these anomalies are familially associated with each other, and, like twinning, familially associated with unusual brain function asymmetry. They affect structures built by fusion of bilateral embryonic halves and remodeled under major influence of neural crest mesenchyme. This conjunction of associations suggests that twinning, symmetry development, and this group of malformations might share causal elements at least some of which are heritable. The problem here is the absence of zygosity differences in these relationships, because of which they cannot be explained within the biology of twinning as it has been understood. A potential resolution is offered by way of a mechanism common to MZ and DZ twinning, involving a relationship between oocyte organization and the determination of body symmetries. PMID- 3330394 TI - [Acute megakaryoblastic leukemia FAB M7]. PMID- 3330395 TI - [Principles of using blood preparations before transplantation of bone marrow]. PMID- 3330398 TI - [Obtaining bone marrow transplants and the preparation of patients for transplantation]. PMID- 3330396 TI - [Selection of bone marrow donors for allogeneic transplantation. General principles]. PMID- 3330397 TI - [Preparation of donors and recipients of bone marrow transplants]. PMID- 3330399 TI - [Removal of erythrocytes from bone marrow preparations by the method of centrifugation in the "liquid for lymphocyte isolation"]. PMID- 3330400 TI - [Prevention and treatment of graft-versus-host disease]. PMID- 3330401 TI - [Basic steps in the procedure of bone marrow transplantation]. PMID- 3330402 TI - [Basic problems of intensive medical care after bone marrow transplantation]. PMID- 3330404 TI - [Disorders of the lips. A comprehensive review]. PMID- 3330403 TI - [Pharmacokinetics of pyronaridine in malaria patients]. PMID- 3330406 TI - Student sketches: Jeffrey C. Thalls. PMID- 3330405 TI - Alumnus close-up: Gregory C. Bell. PMID- 3330407 TI - Bouncing back from heart surgery: personal reflections. PMID- 3330408 TI - Public health & the law. A symposium dedicated to Professor William J. Curran. PMID- 3330409 TI - Access to health care and equal protection of the law: the need for a new heightened scrutiny. AB - Proposals to reduce national expenditures for health care under Medicare and other programs raise questions about the limits on legislative power to distribute health care benefits. The constitutional guarantee of equal protection has been a weak source of protection for the sick, largely because they fail to qualify for special scrutiny under traditional equal protection analysis. Recent decisions of the United States Supreme Court suggest that the Justices seek a newer, more flexible approach to reviewing claims of unequal protection. This Article examines the application of the equal protection guarantee to health related claims. It argues that traditional equal protection analysis is too rigid and newer rationality review too imprecise to provide just eligibility determinations. The Article concludes that courts should subject claims of unequal protection in the health care context to heightened scrutiny, as health care plays a special role in assuring equality of opportunity. PMID- 3330410 TI - Communicable disease and mental health: restrictions of the person. AB - Laws for the protection of public health control either the environment, as in the case of sanitation or air pollution regulations, or human conduct. This Article deals with limitations imposed upon individuals in order to prevent the spread of communicable disease and the harm resulting from mental illness. The restraints discussed include compulsory examination and immunization, and forms of compulsory detention or commitment. This Article is a revised chapter of the author's Public Health Law Manual, first published by the American Public Health Association in 1965. The Manual is intended to help public health professionals to understand the law relevant to their practice, and to apply it more effectively. PMID- 3330411 TI - [Experimental models in chlamydiosis]. AB - The purpose of this review is to present the different animal models developed for the study of chlamydial infection of human and ruminants. PMID- 3330413 TI - Diagnosis and management of early postoperative complications in open heart surgery. AB - Open heart surgery involving the use of artificial prosthetic materials, and extracorporeal circulation for varying periods, is often performed on patients seriously or acutely ill. Despite excellent surgical procedures, various postoperative complications may detract from perfect primary results. Postoperative myocardial failure and cardiac arrhythmias can be expected while vascular accidents and disorders of various organ systems are less common, but serious, complications. The treatment of these complications requires correct diagnosis without delay, their recognition being particularly difficult during the immediate postoperative period. This review deals with the incidence, diagnosis and therapy of the most important early postoperative complications specific to open heart surgery. PMID- 3330412 TI - [Should mammary infections caused by Corynebacterium bovis and coagulase-negative staphylococci be eliminated?]. AB - Role of minor pathogens in resistance to infections: analysis of epidemiological surveys, information obtained by use of experimental infections (role of coagulase-negative staphylococci, and Corynebacterium bovis). Scope of the phenomenon of mammary infections interference. Mechanisms underlying the interference of infections: hypotheses. Consequences for mastitis control. PMID- 3330414 TI - [In vivo and in vitro sensitivity to 4-aminoquinolines of Plasmodium falciparum in Madagascar: results of a study conducted on the east coast (July 1985-July 1986)]. PMID- 3330415 TI - [In vivo and in vitro study of the chemosensitivity of Plasmodium falciparum in Madagascar--1982-1986]. PMID- 3330416 TI - [Resistance of Plasmodium falciparum to 4-aminoquinolines. A review based on the Madagascar experience]. PMID- 3330417 TI - [Convergence, characteristic limit value and data homogeneity as stipulations for the aggregation effect in psychometric data]. PMID- 3330418 TI - [Studies on the mechanism of developing bronchial asthma due to Candida albicans. 5. A comparative study of the mechanisms producing bronchial asthma among Candida, other molds and house dust-induced asthma]. PMID- 3330419 TI - [Diagnosis and therapy of allergic diseases of the mucous membrane of the upper respiratory tract]. PMID- 3330420 TI - Lipid transport through the plasma: the metabolic basis of hyperlipidaemia. AB - Plasma lipid abnormalities derive their importance from their association with coronary artery disease. Elevated cholesterol levels accentuate risk, and clinical trials have shown that reductions lead to a decline in coronary events. The major plasma lipids, cholesterol and triglyceride, circulate in association with specific proteins as lipid-protein or lipoprotein complexes. The proteins direct and regulate the metabolism of these complexes by interacting with tissue enzymes and receptors. The metabolic fate of circulating triglyceride is governed by the activity of the enzyme lipoprotein lipase, situated in adipose tissue and skeletal muscle. Cellular demand for cholesterol, on the other hand, is met by activation of a specific receptor which mediates the delivery of sterol-rich lipoproteins to lysosomal degradation in liver and peripheral tissues. In order to prevent excess cholesterol accumulation at the periphery, there is a system of reverse cholesterol transport which involves assimilation and trapping of the sterol in the plasma lipoproteins through the action of the enzyme lecithin:cholesterol acyltransferase. Thereafter, the cholesterol is delivered to the liver, the only organ capable of excreting it in significant amounts. Disturbances in these processes may produce gross changes in the plasma lipid profile, clearly recognizable as hyperlipidaemia. However, it is becoming increasingly clear that a number of inherited traits can subtly perturb the lipoprotein spectrum and increase coronary risk even in subjects whose plasma lipoprotein profile would be considered normal. PMID- 3330421 TI - Lipoproteins and atherosclerosis. AB - The plasma lipoproteins are the primary means of transport of cholesterol among tissues. In particular, the apo B-containing lipoproteins (VLDL, IDL and LDL) are important for the delivery of cholesterol from the liver to peripheral tissues, while HDL appear to mediate the reverse process of movement of cholesterol from tissues back to the liver. Both of these transport processes are necessary for efficient whole body cholesterol homeostasis, because the liver is the major site of both the production and excretion of cholesterol. However, deviations from a proper balance of transport of cholesterol, either increases in LDL levels or decreases in HDL cholesterol flux, may result in accumulation of cholesterol in extrahepatic tissues. Increased risk of atherosclerosis and CHD may be associated with elevation in the number of LDL particles, increase or decrease in LDL particle size, or changes in the composition of plasma LDL. These modifications of plasma LDL may be brought about following perturbation of one of several aspects of LDL metabolism. These include decreased LDL receptor activity, increased VLDL production and cholesterol enrichment of the liver-derived VLDL. The events in the arterial wall that make some LDL particles apparently atherogenic are not well understood. In the case of nonhuman primates, large-size LDL are associated with an increased risk of CHD. One characteristic of these LDL is that their core lipids are rich in saturated cholesteryl esters and their transition temperatures are frequently above body temperature. The liquid crystalline cholesteryl ester cores of such LDL may modulate the conformation of apo B on the surface and thereby affect the interaction of these LDL with cellular receptors or connective tissue matrix proteoglycans. It is likely, though, that changes in LDL particle number, LDL particle size and LDL particle composition may each contribute to progression of atherosclerosis. The presumed metabolic events that make HDL protective against atherosclerosis have been termed reverse cholesterol transport, and suggest that small HDL that are deficient in free cholesterol acquire this lipid from cell membranes. The HDL cholesterol is esterified by LCAT in the circulation, forming large HDL that can then deliver the cholesteryl ester to the liver by both direct and indirect means. In most circumstances, it is assumed that an increase in plasma HDL cholesterol concentration reflects an increase in the rate at which HDL is removing cholesterol from tissues and, consequently, a decrease in atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3330422 TI - Enzymes involved in plasma cholesterol transport. AB - Regulation of plasma cholesterol transport is to a large extent a function of factors that regulate plasma cholesterol esterification and the transfers of cholesteryl esters between plasma lipoprotein fractions. Plasma cholesterol esterification is catalysed by the action of lecithin: cholesterol acyltransferase on lipids on the surface of HDL, while the transfers of cholesteryl esters require activity of a specific lipid transfer protein. Esterification of the cholesterol on the surface of HDL generates a concentration gradient down which unesterified cholesterol moves from tissues into the plasma. Once within the plasma and esterified, the newly formed cholesteryl esters are incorporated initially into the core of HDL particles before being redistributed to other classes of lipoproteins. The end result of these processes of esterification and transfer is that most of the cholesterol in human plasma is accommodated within the core of LDL, where its transport is a function of the highly regulated uptake by tissues of intact LDL particles. The capacity of HDL to act as substrates for lecithin: cholesterol acyltransferase varies inversely with HDL particle size. Thus, factors such as the concentration of triglyceride rich lipoproteins and activities of the lipid transfer protein, hepatic lipase, lipoprotein lipase and the HDL conversion protein, which are known to influence HDL particle size, may also be important as regulators of plasma cholesterol esterification. PMID- 3330423 TI - Enzymes involved in triglyceride hydrolysis. AB - The lipolytic enzymes LPL and HL play important roles in the metabolism of lipoproteins and participate in lipoprotein interconversions. LPL was originally recognized to be the key enzyme in the hydrolysis of chylomicrons and triglyceride, but it also turned out to be one determinant of HDL concentration in plasma. When LPL activity is high, chylomicrons and VLDL are rapidly removed from circulation and a concomitant rise of the HDL2 occurs. In contrast, low LPL activity impedes the removal of triglyceride-rich particles, resulting in the elevation of serum triglycerides and a decrease of HDL (HDL2). Concordant changes of this kind in LPL and HDL2 are induced by many physiological and pathological perturbations. Finally, the operation of LPL is also essential for the conversion of VLDL to LDL. This apparently clear-cut role of LPL in lipoprotein interconversions is contrasted with the enigmatic actions of HL. The enzyme was originally thought to participate in the catalyses of chylomicron and VLDL remnants generated in the LPL reaction. However, substantial in vitro and in vivo data indicate that HL is a key enzyme in the degradation of plasma HDL (HDL2) in a manner which opposes LPL. A scheme is presented for the complementary actions of the two enzymes in plasma HDL metabolism. In addition, recent studies have attributed a role to HL in the catabolism of triglyceride-rich lipoproteins, particularly those containing apo E. However, this function becomes clinically important only under conditions where the capacity of the LPL-mediated removal system is exceeded. Such a situation may arise when the input of triglyceride rich particles (chylomicrons and/or VLDL) is excessive or LPL activity is decreased or absent. PMID- 3330424 TI - Dietary therapy of hyperlipidaemia. PMID- 3330425 TI - Hormones and lipoprotein metabolism. PMID- 3330426 TI - New horizons in lipoprotein research. AB - The present decade was heralded by the identification of cDNA clones for apo-AI, HMG CoA reductase and the LDL receptor. Today we have descriptions of many other proteins involved in lipid metabolism and of the genes that code for them. Structure and function have been probed by techniques for protein blotting and by in vitro mutagenesis of proteins. The details of gene regulation are now beginning to be unravelled and we can expect exciting new developments in the understanding of how gene expression affects plasma lipoprotein levels. New and powerful techniques have been established for identifying known mutations and for detecting new mutations. Discovery of restriction fragment length polymorphisms have allowed the association between these DNA markers and particular genes involved in lipoprotein metabolism to be probed. The extent to which particular gene loci contribute to the variation in plasma cholesterol levels is being analysed using the methods of genetic epidemiology. With the advent of methods for establishing linkage and physical maps of the human genome, it is now possible to identify the genes responsible for any disorder in which clinical material can be assembled. From this rapidly advancing knowledge it must be anticipated that many new exciting diagnostic and therapeutic possibilities will emerge. PMID- 3330427 TI - Use of adipose tissue for metabolic studies. AB - Open biopsy of adipose tissue from volunteer subjects has led to a greater understanding of the mechanisms of adipose-tissue insulin resistance in various clinical states. Studies of adipose tissue obtained during surgical operations have allowed development of techniques and exploration of adipocyte physiology. This has been particularly valuable in examining the relationship between cellular insulin binding and action. Examination of the lipid stores and of enzyme activities has been possible by using the more convenient technique of needle biopsy. Regional differences in adipose tissue metabolism have been identified and must be considered in experimental design. It is now clear that the insulin sensitivity of any one metabolic pathway does not necessarily reflect that of others, and care must be taken to avoid inappropriate extrapolation of data both between metabolic pathways in the adipocyte itself and from the adipocyte to the whole body. PMID- 3330428 TI - Measurement of circulating intermediary metabolites. PMID- 3330429 TI - Measurement of the turnover of substrates of carbohydrate and protein metabolism using radioactive isotopes. AB - The rate of turnover of glucose or leucine can be measured in the steady state by using the radioactive isotopes 14C or 3H to 'trace' these metabolites. The tracer can either be injected or infused intravenously and its metabolism followed by monitoring levels of the tracer in blood, breath and urine. If a 14C labelled metabolite is used the oxidation rate may sometimes be determined by measuring the expiry rate of 14CO2. If the single injection technique is used the specific activity curve is fitted with an exponential function and the area under the curve calculated. Turnover rate is calculated from dose of isotope injected/area under the specific activity time curve. This technique can be used to construct a compartmental model to describe the behaviour of the metabolite. If the constant infusion technique is used, tracer is infused until a steady state level of tracer is achieved. This plateau is used to calculate the turnover of the metabolite from infusion rate of tracer/specific activity at steady state. While this latter method provides the simplest method of calculating turnover it cannot be used to model the data. The infusion technique can be used to measure changes in turnover and oxidation in the non-steady state. Tracer is infused to a steady state level and the system is then perturbed by for example, the infusion of a hormone. The changes in Ra and Rd can be determined either by using the Steele equation which assumes a single pool or by using compartmental analysis. PMID- 3330430 TI - The use of isotopic tracers in studying lipid metabolism in human subjects. AB - We have attempted to evaluate some of the tracer methodologies involved in studying lipid metabolism in humans. The magnitude of this subject prohibits a comprehensive review of all areas. Since the major function of adipose tissue appears to be to supply the body with energy, we have particularly emphasized the approaches used to study the mobilization and oxidation of fat. The importance of these issues, as well as the increasing availability of non-radioactive tracers, suggest an optimistic future for this area of research. PMID- 3330431 TI - The use of stable isotopes in metabolic investigation. AB - The use of tracers to define substrate dynamics has been the sine qua non of metabolic investigation in vivo, because static measurements of substrate content alone are inadequate. The judicious use of radioactively labelled compounds remains the principal tracer approach in some adult subjects. However, in certain young adults, in pregnant women and in children, stable isotope tracers offer a practical alternative for answering important metabolic questions. In the last decade, the developmental problems previously associated with employing stable isotope tracers for this purpose have largely disappeared. Furthermore, the use of stable isotopically labelled materials offers certain additional advantages which are either difficult or impossible to achieve using radiotracers. These include the ability to measure simultaneously substrate content and isotopic enrichment with very high specificity and precision, the ability to determine the intramolecular location of the label, the ability to use the mass of the stable isotope substrate as a probe of the metabolite system response to perturbation, and the ability to study simultaneously and repeatedly the same subject with multiple substrate tracers. The practical application of these principles has been amply demonstrated by the expanding use of non-radioactive tracers to study body composition, energy balance, and the inter-organ transport and oxidation of the three major metabolic fuels--glucose, fat and amino acids. Continued development in the organic synthesis of new, stable isotopically labelled biochemicals will allow investigation of additional areas of biomedical importance which have been hitherto inaccessible to this approach, particularly in the pathophysiology of metabolic events in the growing child. PMID- 3330432 TI - Use of the splanchnic/hepatic balance technique in the study of glucose metabolism. AB - This chapter examined the applicability of the splanchnic/hepatic balance technique to the study of glucose metabolism in humans and in dogs. When combined with radioisotope turnover methodology, the hepatic/portal venous catheterization technique provides a powerful tool to investigate splanchnic/hepatic carbohydrate metabolism. It should be emphasized that the same principles described on the preceding pages can be applied to study amino acids (Gelfand et al, 1986), potassium (DeFronzo et al, 1980) and insulin (Ferrannini et al, 1983), as well as a variety of other metabolites and hormones. PMID- 3330433 TI - The measurement of metabolite exchange across muscle beds. PMID- 3330434 TI - Insulin sensitivity in the intact organism. AB - Insulin resistance is a classic characteristic of type II diabetes. Precise quantification of insulin sensitivity in vivo is essential for elucidation of the pathogenesis of observed glucose intolerance. The euglycaemic glucose clamp of Andres and colleagues assesses insulin action by disrupting the negative feedback relationship of glucose and insulin. Insulin is infused, but euglycaemia is maintained by exogenous glucose infusion (GINF). At steady state, GINF (M) represents total insulin action, i.e. suppression of hepatic glucose output (HGO) plus acceleration of peripheral uptake (Rd). Coupled with the isotope dilution techniques of Steele et al, these hepatic and peripheral effects can be partitioned, although this approach may underestimate HGO and Rd. Modifications of the Steele method may be required for more reliable quantification of glucose turnover. The dose-response relationship between insulin and Rd also provides a measure of sensitivity from the glucose clamp: the ED50 (and Rdmax), analogous to the Km and Vmax of Michaelis-Menten analysis. However, extensive labour requirements, cost and difficulties in ED50 estimation limit its widespread use. Glucose clearance (Rd/G) has also been used to assess insulin sensitivity in subjects of differing glycaemia, but because it fails to rise in proportion to glucose it is an inappropriate measure. Hence, we have introduced the insulin sensitivity index SIP(clamp), defined as the action of insulin to increase glucose clearance (delta Rd/(G delta I], which is independent of prevailing glycaemia and insulinaemia. Lastly, we proposed the minimal model method, which determines insulin sensitivity (SI) from analysis of the simple intravenous glucose tolerance test (IVGTT). By adding tolbutamide injection after glucose, the resultant model-based SI is equivalent to SIP(clamp). Furthermore, minimal model analysis will also yield SG, the parameter of insulin-independent glucose disappearance. We conclude that assessment of insulin sensitivity, whilst important, must be considered in the context of its relation to pancreatic function and insulin-dependent glucose disappearance. Only a clear understanding of the complex interrelation of these factors will lead to elucidation of the mechanisms underlying glucose intolerance. PMID- 3330435 TI - Indirect calorimetry. AB - Indirect calorimetry is a method which allows the non-invasive measurement of energy expenditure and substrate utilization in humans. The procedure is described and the main equations to calculate energy expenditure and substrate utilization are presented. The limitations of the method include physiological effects, such as hyperventilation, and the influence of metabolic processes such as gluconeogenesis, ketogenesis and lipogenesis. The general principle is that intermediate processes do not influence overall conclusions, provided that the intermediate substrates which are formed do not accumulate within the body or are not excreted. Continuous measurements of metabolic rate and respiratory quotient using the ventilated hood system have been carried out during the last 5 years to study carbohydrate and lipid metabolism in lean subjects, in obese and diabetic patients. By using the euglycaemic insulin clamp technique or by giving oral glucose loads, it has been shown that the main effect of insulin on carbohydrate metabolism is to stimulate glucose storage. By raising plasma free fatty acid levels with a neutral fat infusion in lean subjects, both glucose oxidation and glucose storage were imparied during euglycaemic insulin clamps. Glucose storage was found to be markedly impaired in non-diabetic obese patients, during euglycaemic insulin clamps in the presence of elevated lipid oxidation. In obese diabetic patients, the impairment in glucose storage was more pronounced than in non-diabetic obese; this defect was particularly marked during euglycaemic insulin clamps, but it was also present after an oral glucose load. It is concluded that impairment of glucose storage is a major defect of glucose utilization in type II diabetes. PMID- 3330436 TI - NMR as a metabolic tool. AB - We have briefly reviewed the broad range of applications of NMR spectroscopy to metabolism in tissues and biological fluids. Most of these studies are in the exploratory stage, though the potential of NMR for non-invasive and non destructive monitoring of certain important substrates and reaction pathways is considerable. The limitations of the technique lie in its relative insensitivity and the rather restricted range of substances that it can detect, as well as the current expense. So far, the main clinically useful applications have been in the diagnosis and monitoring of treatment of certain inborn errors of metabolism, namely those that result in altered energy of pH states or the abnormal accumulation of significant amounts of metabolites in body fluids. It might be expected that as localization techniques improve, clinically useful information will be obtained in a wide range of ischaemic or hypoxic states, e.g. stroke and myocardial infarction. The possibility of producing a detailed spatial image of metabolite concentrations (e.g. ATP), in the way that NMR imaging techniques currently do using features of the water proton resonance, is attractive and the initial results are very encouraging (Bogusky et al, 1986; Bailes et al, 1987; Blackledge et al, 1987). PMID- 3330438 TI - Human liver in vitro techniques for metabolic studies. PMID- 3330437 TI - Metabolic studies using isolated skeletal muscle: investigation of metabolic myopathies. PMID- 3330439 TI - The maturation and recognition of the functional image. PMID- 3330440 TI - Radiolabelled monoclonal antibodies for the detection of cancer. AB - Methods currently available to the clinician for the detection and localization of cancer are not specific and may have reached their technical limits. Deficiencies of these methods are detailed, and an ideal system for cancer detection is presented. Monoclonal antibodies directed against tumor antigens and labelled with radionuclides approach the ideal as a method for cancer screening, detection, localization, monitoring, and, perhaps, therapy. The production and radiolabelling of monoclonal antibodies are reviewed, and recent technical developments for imaging are explained. Methods to manipulate the system to achieve specific goals are outlined, and examples are shown. Metastases of certain tumors are demonstrated. The method holds great potential for diagnosis, monitoring, and even for radiotherapy of target tumors. Clinical trials are now in progress. PMID- 3330441 TI - The study of cerebral ischemic reversibility: Part I. A review of positron imaging studies. AB - Predictions about tissue viability and clinical recovery following cerebral ischemic events can be more accurately made once quantitative information is available regarding cerebral blood flow and concomitant cerebral metabolism. To date, positron imaging data has, on a limited basis, been available in regional centers and has helped determine issues of ischemic reversibility. The stages of cerebral ischemia are reviewed along with the physiologic data available via positron imaging. Expansion of this data base by studying the natural history of ischemic lesions with follow-up studies and by studying individuals before and after intervention therapies is the next step in further understanding the pathophysiology of cerebral ischemia. PMID- 3330443 TI - Exercise-induced renal dysfunction studied by 99mTc-DTPA in hypertensives and normotensive controls. AB - With the purpose of studying the effect of exercise on renal function in hypertensive patients, renal dynamic studies were performed with the aid of 99mTc diethylenetriamine pentaacetate (DTPA). Serial renal images were taken at rest and during bicycle ergometric stress in 14 hypertensive patients (H) and 14 normotensive controls (N). Renograms were constructed, and glomerular filtration rate was determined by the method of Gates [2]. Exercise resulted in a prolongation of peak time, an increase in radioisotope retention rate at 10 minutes (10-min counts/peak counts) on renograms, and a decrease of GFR in both H and N. Plasma renin activity, aldosterone, and catecholamines were all elevated during exercise in both H and N. Our data indicate that the exercise-induced renal dysfunction demonstrated by 99mTc-DTPA renograms is not specific to H but can also be observed in N, which may have resulted from changes common to H and N, as indicated by the change of GFR and humoral factors. These findings suggest that the renal response to exercise may be a more complex pathophysiologic process than that measured by the DTPA renogram, at least in its simplified form, and should encourage further work in this area in order to elucidate the underlying process of hypertension. PMID- 3330442 TI - Quantitative comparison of regional distributions of inhaled Tc-99m DTPA aerosol and Kr-81m gas in coal miners' lungs. AB - Regional distributions of deposited Tc-99m diethylenetriamine pentaacetate aerosol (DPTA) and of Kr-81m were compared in the upright lungs of 22 coal miners with nonembolic pulmonary disease. Pixel-by-pixel distributions of Kr-81m and DPTA corrected for lung volume, as well as DTPA/Kr-81m ratios, were determined by computer analysis in each lung and plotted against lung position. DTPA was preferentially deposited in the basal regions of 36/44 lungs. In the same lungs, Kr-81m was preferentially distributed in the apical regions of 18 lungs, bilaterally in six subjects. Similar DTPA and Kr-81m regional distributions throughout both lungs were obtained in only 11 (50%) subjects. No significant correlations were found between regional particle deposition and pulmonary function measurements. The effects of gravity-related lung pressure gradients and ventilation-related particle residence time on the deposition of DTPA may limit its usefulness when quantitative information is required to evaluate subtle changes in ventilation in nonembolic pulmonary patients and for basic studies of ventilation and perfusion. PMID- 3330445 TI - Radiolabeled meta-iodobenzylguanidine: pharmacology and clinical studies. AB - Much was known of the pharmacology of meta-iodobenzylguanidine (MIBG) before its clinical use, but we have since learned a good deal more about the metabolic distribution and fate of this radiopharmaceutical. And, as is the nature of science, more is yet to be discovered. This communication reviews what is known about the pharmacology of radiolabeled MIBG and how this pharmacology affects the clinical studies that use the agent. PMID- 3330444 TI - Scintigraphy of the female breast with Tc-99m-DTPA: a prospective blind evaluation. AB - Following a report on the use of Tc-99m-diethylenetriamine pentaacetic acid (Tc 99m-DTPA) for detection of malignant breast tumors we compared this method with other diagnostic aids such as mammography and cytology. Among 160 women referred to our department for diagnosis, 166 examinations were performed (six patients had bilateral lesions); the final diagnosis of the breast lesion was established as malignant in 62 cases and benign in 104 cases. The scintigraphic image was reported malignant if an area of focal uptake observed on the scan 30 minutes after injection of the tracer persisted or became more intense on the 2-hour scintigram. All other uptake patterns were considered benign. For this examination we obtained a sensitivity of 75% and a specificity of 91%. For mammography, sensitivity was 90% and specificity was 82%. The lower false positive results of scintigraphy may serve to confirm the benignancy of doubtful mammographic findings, for when both examinations suggest a benign lesion, the combined imaging procedure is a useful means of excluding cancer (sensitivity 96%, predictive value 98%). It is concluded that in all other cases Tc-99m-DTPA breast scintigraphy is of limited value. PMID- 3330446 TI - Current and future role of noninvasive studies in acute myocardial ischemia and infarction. AB - During the last 10 years, the pathophysiologic events that follow acute interruption of coronary arterial flow have been extensively worked out. It is now known that the ultimate size of acute myocardial infarction is a function of time after occlusion, size of the arterial territory deprived of arterial blood (area-at-risk), and available collateral flow at the time of occlusion. These concepts are the basis for application of medical therapies, e.g., reperfusion by thrombolysis, which are designed to limit infarct size. Noninvasive imaging aimed at assessing acute myocardial ischemia and infarction is the subject of this review. Potentials and limitations of gamma-radiation single photon emission computed tomography, positron-emission computed tomography, and nuclear magnetic resonance (NMR) spectroscopy are discussed in this review within the context of the known pathophysiology of acute ischemic events. PMID- 3330447 TI - Medical imaging of the parathyroid glands. AB - In patients with hyperparathyroidism, the detection and localization of parathyroid lesions can aid the surgeon preoperatively and prior to re exploration if the initial surgery fails. Computed tomography, ultrasound, and radionuclide scintigraphy are currently most commonly used to evaluate the parathyroid glands in patients with hyperparathyroidism. This article will review the experience, techniques, and advantages of these respective imaging modalities in the evaluation of parathyroid lesions. PMID- 3330449 TI - Radionuclide ventriculography: I. Technical aspects. AB - Radionuclide ventriculography is a relatively simple, easily repeatable technique for the noninvasive assessment of global and regional ventricular function. Since the initial description of radionuclide ventriculography over 15 years ago, it has found widespread application in the diagnosis and evaluation of patients with coronary, valvular, myopathic, and congenital heart disease. This manuscript, the first of two parts, reviews the technical aspects of radionuclide ventriculography, including both gated equilibrium and first-pass methods. The available radiopharmaceuticals, the necessary equipment, and the most reliable procedures are described. The strengths and weaknesses of both methods are compared, including their relative resolutions, the acquisition times required, the variables that may be measured, and the repeatability of each. Finally, the most recent development in radionuclide imaging of the cardiac blood pool, gated tomographic imaging, is described, and its potential clinical applications and advantages are discussed. PMID- 3330448 TI - Experimental basis of metabolic imaging of the myocardium with radioiodinated aromatic free fatty acids. AB - For the investigation of myocardial perfusion and left ventricular pump function, advanced radioisotopic techniques have been established. New developments in radiopharmacology and single-photon emission computed tomography have recently enabled the investigation of parameters of regional energy metabolism in well defined areas of the heart muscle. For this purpose, various iodine (123I) labeled free fatty acids (FFA) have been synthesized. The diagnostic application of labeled FFA in heart disease may be important, since FFA are the preferred substrates for cardiac energy production at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with beta-oxidation which is extremely sensitive to oxygen deprivation. This article outlines the basic physiologic pathways of FFA in normal and ischemic myocardium and reviews the results of animal experiments validating the application of these principles for metabolic imaging of the heart by means of the aromatic radioiodinated FFA, 15-(p iodophenyl)pentadecanoic acid. In addition, the development, physiologic properties, and potential applications of a new generation of 3-methyl substituted radioiodinated fatty acids that show high myocardial uptake but prolonged retention are discussed. PMID- 3330450 TI - Background in the 99mTc DTPA renogram: analysis of intravascular and extravascular components. AB - Individual kidney glomerular filtration rate (IKGFR) was calculated from the upslope of the 99mTc-diethylenetriamine pentaacetic acid (DTPA) renogram in ten children with a normal solitary kidney (on the right in five and on the left in five). By using a method of renogram analysis that is independent of the intravascular (IV) component of background (BG) activity, the IV and extravascular (EV) components of background were separately quantified in various regions in proximity to the nephrectomy site. The size of the IV compartment was expressed as an absolute plasma volume (PV-BG), and that of the EV compartment was expressed as a "GFR equivalent," i.e., the undirectional rate of fluid transfer from the IV to EV spaces in ml per min (GFR-BG). The region areas from which these parameters were calculated were normalised to the area projected by the solitary kidney. In a region centred over the lower pole of the imagined absent kidney, PV-BG was 129 +/- 7 ml (SE) and GFR-BG was 28 +/- 1.8 ml per min. The corresponding values centred over the liver/spleen on the nephrectomised side were 353 +/- 24 ml and -2 +/- 2.9 ml per min, respectively. PV-BG, but not GFR BG, was significantly higher over the liver (397 ml and -6.8 +/- 1.5 ml per min) compared with the spleen (287 ml, P less than .05; and 4.5 +/- 3.2 ml per min, P greater than .05). PV-BG and GFR-BG in a region placed over the centre of the nephrectomy site were intermediate between those superior and inferior: 231 +/- 17 ml and 15 +/- 2.7 ml per min, respectively. The IV signal rises while the EV falls during the second phase of the renogram. In the analysis of the renogram during this phase, therefore, background should be based on both supra- and subrenal regions of interest. PMID- 3330451 TI - Radionuclide ventriculography: II. Anatomic and physiologic aspects. AB - Radionuclide ventriculography is a widely applied noninvasive technique for the assessment of global and regional ventricular function. In this manuscript, the second of a two-part review of radionuclide ventriculography, the analysis of the images provided by these studies and their clinical applications are discussed. A description of the anatomic information that may be gleaned from the evaluation of the size and shape of the cardiac blood pool and the contiguous vessels is included. The quantitative methods available for the analysis of radionuclide ventriculograms and the several variables that may be measured are discussed. These methods include measurements of global and regional systolic ventricular function and of global diastolic ventricular function. Finally, the clinical applications of radionuclide ventriculography are described. These applications include the diagnosis of coronary artery disease, both acute and chronic, and evaluations of prognosis and therapeutic response in patients with coronary artery disease, valvular heart disease, especially regurgitant lesions, and myopathic heart diseases, particularly dilated and hypertrophic cardiomyopathies. PMID- 3330452 TI - Photon absorptiometry. AB - Recently, there has been a renewed interest in the detection and treatment of osteoporosis. This paper is a review of the merits and limitations of the various noninvasive modalities currently available for the measurement of bone mineral density with special emphasis placed upon the nuclear medicine techniques of single-photon and dual-photon absorptiometry. The clinicians should come away with an understanding of the relative advantages and disadvantages of photon absorptiometry and its optimal clinical application. PMID- 3330453 TI - Physiologic imaging of radiolabeled leukocytes. AB - The radiolabeling of leukocytes and other cellular elements of the blood has allowed a number of physiologic processes to be investigated. In addition, many commonly performed clinical nuclear medicine procedures utilize these techniques. The following is a review of the labeling technique and of the utility of radiolabeled leukocytes. PMID- 3330454 TI - Quantitative positron emission tomography and single photon emission computed tomography measurements of human cerebral blood flow. AB - Current methods using emission tomography to quantitate human regional cerebral blood flow (rCBF) are reviewed. The sensitivity and spatial resolution of single photon emission tomography are too low to correlate reliably rCBF with known anatomic landmarks in the brain. However, even if the superior imaging qualities of positron emission tomography are employed, the radiotracers of rCBF frequently do not fully meet the requirements of the models of tracer kinetics that are employed. Therefore, the methodology of reported rCBF studies using emission tomography to measure quantitatively human rCBF needs to be carefully evaluated. PMID- 3330455 TI - Double-blind comparison of Inderal LA (160 mg), Half-Inderal LA (80 mg), and Half Inderal LA plus bendrofluazide (2.5 mg) in the treatment of elderly hypertensive patients. PMID- 3330456 TI - Thrombolysis and myocardial infarction. AB - Many studies suggested that the administration of streptokinase (SK) via a coronary catheter or with intravenous treatment is effective in lysing the offending thrombus which is the cause of most acute myocardial infarctions (AMI). The research carried out by the Italian Group for the Study of Streptokinase in Infarct (GISSI) which enrolled a central randomised population of 11,712 patients with AMI, clearly suggests: intravenous infusion of 1.5 million units of SK reduces in-hospital mortality from 13% to 10.7% (P = 0.0002); the decrease in mortality is 47% in patients treated within 1 hour after the onset of pain. The incidence of adverse reaction was low (4.7%). The results of the follow-up (12 months) demonstrate that beneficial effects of SK treatment on mortality were unchanged. Analysis of plasma creatine kinase curves (CK) from 7,632 patients demonstrates that the rate of input and disappearance of CK into the blood was significantly increased in SK patients. In elderly patients (greater than 65 years) the in-hospital mortality was higher (22.4% vs. 7.4%): SK is effective in patients with first AMI (19.1% vs. 22.9%). The incidence of reinfarction in the hospital phase and at the six months follow-up is higher in SK group (7.4% vs. 4.4%). Some questions remain open about the therapeutical approach to the post thrombolytic phase and about the treatment of residual stenosis. PMID- 3330457 TI - Intraperitoneal chemotherapy for ovarian carcinoma. AB - Investigators at several centers have begun to explore the potential utility of the intraperitoneal administration of chemotherapeutic agents as therapy for advanced ovarian carcinoma. Recent pharmacokinetic modeling studies have suggested and initial clinical trials have confirmed an advantage for cavity exposure to certain drugs compared to systemic exposure when the agents are delivered directly into the peritoneal cavity. While objective responses have been observed in patients with refractory disease, there are both practical and theoretical problems with this approach to the treatment of ovarian carcinoma. Eventually randomized controlled trials will be required to define a role for this innovative therapeutic technique. PMID- 3330458 TI - Sequential determination of IgG subclasses and IgA specific antibodies in primary and reactivating toxoplasmosis. AB - During the course of T. gondii infection, we have analysed serum IgG and IgA antibodies responses in 50 immunocompetent with acquired infection and 19 immunocompromised patients with evidence of reactivated toxoplasmosis. Using an ELISA, IgG1, IgG2, IgG3 and IgA antibodies were found in sera of all patients, whereas IgG4 antibodies were usually not detectable. In immunocompetent patients, the predominant antibody isotype was IgG1 at the different stages of infection, presumably in relation with a T-cell control of humoral response during toxoplasmosis. In immunocompromised hosts (kidney or bone marrow transplanted and HIV infected patients), a sequential study was performed on serum samples taken before and after reactivation had occurred. The isotypic distribution of antibodies was similar to that observed in immunocompetent patients, but differences between groups of immunocompromised patients were detected when the kinetics of the antibody response was considered. The IgG and IgA antibody rise was lower in HIV1 infected patients with clinical toxoplasmosis; whatever was the peak antibody value, clinical symptoms appeared earlier in patients with a slower antibody response. This presumably reveals a functional T-cell abnormality, which may rely to the defective containment of the parasite in these patients. PMID- 3330459 TI - [Effects of vaccination in urinary infections caused by Escherichia coli in rats]. AB - The preventive effects of the immunomodulator P40 on the experimental E. coli infection of the lower urinary tract of the rat have been reported previously. In the present paper are presented the results obtained with the aid of vaccination using the same experimental model of infection in the rat. Active specific immunization of the animals with a vaccine consisting of the same strain as that used for infecting the rats afforded significant protection toward the infection. It is concluded that such vaccines could also be used in humans, either alone or in combination with other therapies with the aim at preventing recurrencies or relapses of infections of the lower urinary tract which were resistant to antibiotherapy. PMID- 3330460 TI - Effects of a high-carbohydrate diet on blood glucose, insulin and triglyceride levels in normal and obese subjects and in obese subjects with impaired glucose tolerance. AB - 1. The present study was performed in order to assess the influence of a high carbohydrate diet on carbohydrate and lipid metabolism in humans. 2. Short-term (3 weeks) and long-term (6 weeks) effects of a high-carbohydrate diet (HCD, 85% carbohydrate) were compared with the effects of 2 weeks on a diet of normal carbohydrate content (ND, 45% carbohydrate). The study was conducted on 4 normal and 11 obese subjects (with normal or impaired glucose tolerance) on a metabolic ward. Fasting blood glucose, insulin and triglyceride levels were measured twice a week. Tolerance to carbohydrates was evaluated by measuring blood glucose and insulin levels after oral and intravenous glucose loads and liquid meals at intervals throughout the 8-week period. 3. Long-term HCD improved the tolerance to oral glucose, i.e., it decreased serum glucose and insulin responses to an oral glucose load. 4. HCD had no effects on fasting levels of glucose or insulin or on the tolerance to an intravenous glucose load. 5. A high-carbohydrate liquid meal induced greater post-prandial glucose and insulin levels than a normal liquid meal. 6. In a second group of 6 normal and 6 obese subjects, efficacy of the liquid meal tests was evaluated. A high-carbohydrate liquid meal induced greater glucose and insulin responses than a normal liquid meal during both dietary periods. 7. Fasting triglyceride levels increased and remained high throughout the HCD period. PMID- 3330461 TI - Absence of mutagenicity of Potomorphe umbellata and Potomorphe peltata in the Salmonella/mammalian-microsome mutagenicity assay. AB - The development of short term tests for measuring the mutagenic activity of genotoxic chemicals has been helpful in increasing security. Natural products from the flora are largely used in popular medicine. Using the Salmonella/mammalian-microsome assay, we investigated the genetic toxicity of two plant species popularly used in malaria treatment, Pothomorphe umbellata and Pothomorphe peltata. The data show the absence of genetic toxicity for both plant species. PMID- 3330462 TI - Hyaluronidase activity of group B streptococci. AB - Extracellular hyaluronidase produced by the clinical isolates of various serotypes of group B streptococci was studied using a sensitive spectrophotometric micromethod. Enzyme activity, up to 4.6 units per optical (Klett) density unit of the bacterial suspension was present in the culture supernatants of 38 of the 39 strains tested. There was no association between high levels of hyaluronidase activity and specific serotypes or clinical sources of strains. PMID- 3330463 TI - Thyroxine (T4) and triiodothyronine (T3) metabolism in normal subjects from Rio de Janeiro, Brazil. AB - Kinetic studies of T4 and T3 metabolism were performed on 5 healthy volunteers from Rio de Janeiro to obtain normal values for thyroid hormone metabolism. 125I T4 and 131I-T3 were administered in bolus and blood samples taken during 7 days. Circulating tracers were isolated by Sephadex G-25 chromatography. The kinetic parameters of T4 and T3 metabolism were calculated by noncompartmental methods. Metabolic clearance rates were 1.04 l/day for T4 and 20.7 l/day for T3. The daily production rate was estimated at 94 micrograms/day for T4 and 23 micrograms/day for T3 and their exchangeable pools at 914 micrograms and 25.5 micrograms, respectively. These values are well within the range of those reported by North American or European authors for normal subjects. PMID- 3330464 TI - Regional dipyrone nociceptor blockade: a pilot study. AB - Eighteen of nineteen patients reported relief from chronic pain (40 to 100%, analogue scale) lasting from a few hours to up to two months after single or repeated regional infusion of dipyrone into a limb. A tendency towards increased duration of pain relief was observed after repeated infusions. The present series of observations in man and experiments with rat paw hyperalgesia are consistent with the interpretation that dipyrone blocks a persistent hyperalgesic state which may result from a previous frequent nociceptive stimulation (memory?) rather than an ongoing inflammatory process. PMID- 3330465 TI - [Precision and comparative stability of 3 removable die systems]. PMID- 3330466 TI - [Bonded bridges with vertical insertion: choice of path of insertion and study of preparation of abutments]. PMID- 3330467 TI - [Critical study of circumferential clasps with mesial emergence. Analytical calculation and the determination of fulcrum points photoelasticity ]. PMID- 3330470 TI - Enzyme labeling of steroids by the N-succinimidyl ester method. Preparation of glucose oxidase-labeled antigen for use in enzyme immunoassay. PMID- 3330469 TI - Specific inhibitors implicate a soluble metalloendoproteinase in exocytosis. AB - 1. Previous studies have demonstrated that exocytosis in adrenal chromaffin cells appears to require zinc-dependent endoproteinase activity. 2. Chromaffin cells have metal-dependent endoproteinases in both the plasma membrane and the soluble fraction of homogenized cells. In order to further study critically the role of metalloproteinase in exocytosis, and prior to purification, we needed to determine which one of several adrenal metalloproteinases is implicated in exocytosis. 3. The studies described here demonstrate that the metal-dependent endoproteinases in these two subcellular fractions can be differentiated by selective inhibitors. In both intact and permeabilized cells, the plasma membrane metalloproteinase, but not the soluble proteinases, is inhibited by phosphoramidon. Phosphoramidon does not block exocytosis in either intact or permeabilized cells. 4. In addition, the plasma membrane metalloproteinase appears to have its catalytic site facing the outside of the cell. 5. Because of these observations the plasma membrane metalloproteinase does not appear to be required in exocytosis. Since soluble metalloproteinase activity is inhibited by proteinase inhibitors at concentrations which block exocytosis, a soluble, and not the plasma membrane, metalloproteinase appears to be required in exocytosis. PMID- 3330471 TI - Overproduction of cellular and activated Ha-ras proteins by mutating a synthetic gene. PMID- 3330468 TI - The enkephalin-containing cell: strategies for polypeptide synthesis and secretion throughout the neuroendocrine system. AB - 1. Enkephalinergic cells are found throughout the diffuse neuroendocrine system, in the adrenal medulla, brain, spinal cord, peripheral and enteric nervous systems, and endocrine pancreas. 2. In each of these diverse cell types, the enkephalin phenotype is (i) established during development, (ii) modified by the particular environment in which the cell is located, and (iii) maintained by ongoing biosynthesis at a rate consistent with loss of enkephalins from the cell during periods of secretion. 3. Enkephalin expression and biosynthesis have been studied in several neuroendocrine cell types and tumor cell lines. Transcriptional, translational, and posttranslational factors can play a role at all three stages (establishment, modification, and maintenance) in the regulation of enkephalin expression during the lifetime of the cell. 4. Cyclic nucleotides, glucocorticoids, and calcium may all act to control the overall level of enkephalin biosynthesis pretranslationally, while regulation of posttranslational processing of proenkephalin seems to be important in determining the pattern of proenkephalin-derived opiate peptides produced in a given tissue. 5. The themes (and variations) of cell regulation that apply to enkephalin expression may be similar for other bioactive peptides produced in neural and endocrine tissues. PMID- 3330472 TI - Isolation and characterization of protease modified ribonucleases from Rhizopus sp. PMID- 3330473 TI - [Treatment of fractures of the orbit floor by a double-route approach with eventual use of a bone graft]. PMID- 3330474 TI - [Lortat-Jacob disease and ocular lesions. Apropos of a case]. PMID- 3330475 TI - [Ophthalmologic problems in pregnancy]. PMID- 3330476 TI - [Necrotizing ulcerous gingivitis and progressive periodontitis in HIV infection]. PMID- 3330477 TI - [Hematogenic contact dermatitis to nickel ions in a Septopal minichain]. PMID- 3330479 TI - [Solitary bone cysts of the jaw]. PMID- 3330478 TI - [Long-term observation over 12 years following endoprosthetic TMJ replacement]. PMID- 3330480 TI - [Radial forearm flap with neurovascular anastomosis for skin, mucosa and nerve replacement]. PMID- 3330481 TI - [Revascularized transfer]. PMID- 3330483 TI - Peritoneal dialysis and haemodialysis in pregnancy. PMID- 3330482 TI - [Reconstruction of the mandible and maxilla with bone. A report on 115 cases]. PMID- 3330484 TI - Pregnancy in renal allograft recipients: prognosis and management. AB - Renal transplantation is invariably accompanied by improvements in reproductive function. The possibility of conception in women of childbearing age emphasizes the need for compassionate and comprehensive counselling. Couples who want a child should be encouraged to discuss all the implications. Therapeutic abortion is undertaken in 22% of conceptions and the spontaneous abortion rate is about 16%, the same as for the normal population. Of the conceptions that continue beyond the first trimester, over 90% end successfully. In most women, renal function is augmented during pregnancy, but permanent impairment occurs in 15% of pregnancies. In others there may be transient deterioration in late pregnancy (with or without proteinuria). There is a 30% chance of developing hypertension, pre-eclampsia or both. Preterm delivery occurs in 45-60%, and intrauterine growth retardation in at least 20% of pregnancies. Despite its pelvic location, the transplanted kidney rarely produces dystocia and is not injured during vaginal delivery. Caesarean section should be reserved for obstetric reasons only. Neonatal complications include respiratory distress syndrome, leucopaenia, thrombocytopaenia, adrenocortical insufficiency and infection. No predominant or frequent developmental abnormalities have been described and data on infancy and childhood are encouraging. For the future, clinical and laboratory research are essential in order to improve prepregnancy assessment criteria, to understand the mechanisms of gestational renal dysfunction and proteinuria, to assess the side effects and implications of immunosuppression in pregnancy and to learn more about the remote effects of pregnancy on both renal prognosis and the offspring. PMID- 3330485 TI - Renal haemodynamics and tubular function in human pregnancy. AB - In human pregnancy, effective renal plasma flow and glomerular filtration rate increase to levels 50-80% above non-pregnant values. The increments occur shortly after conception, persist throughout the second trimester and reduce slightly in late pregnancy. The hyperfiltration of pregnancy does not seem to be a potentially damaging process. The increased excretion of glucose and other nutrients, as well as uric acid and protein, is related in part to altered tubular function. Renal physiology is altered so much in pregnancy that non pregnant norms cannot be used in antenatal care. PMID- 3330487 TI - Renal tubular function in the gravid rat. AB - Pregnancy in the rat is accompanied by enhanced reabsorption of salt and water throughout most, if not all, of the gestational period. Many mechanisms have been suggested but definitive answers are still awaited. The major area of controversy centres around the detection of changes at term. There is general agreement that, at least in mid-gestation, the increase in reabsorption can be attributed to increases in the proximal tubules, the loop of Henle and collecting duct. The contribution of the proximal tubule to the increased reabsorption at term is still uncertain. Enhanced salt and water reabsorption is demonstrated in distal nephron segments irrespective of the stage of gestation. Micropuncture and microperfusion experiments have identified increased reabsorption of water, sodium and chloride in the loop of Henle, but it appears that there is net addition of glucose, urea and potassium to the tubular fluid in this segment which, at least for potassium and glucose, offsets to some extent increased reabsorption by the proximal tubule. Altered renal handling of other solutes (uric acid, calcium and magnesium) also occurs throughout pregnancy but the mechanisms responsible and nephron sites involved remain to be investigated. Attempts to attribute altered reabsorption to direct renal effects of changes in maternal hormones are inconclusive. Prolactin mimics some of the pregnancy associated increases in reabsorption following chronic administration to male and non-pregnant female rats. These effects might be due to a direct renal action of the hormone or even to the volume expansion following its dipsogenic action. PMID- 3330486 TI - Glomerular filtration and volume regulation in gravid animal models. AB - The gestational increase in glomerular filtration rate (GFR) that occurs in the normal rat is the result exclusively of an increase in plasma flow rate, and there is no sustained increase in glomerular capillary blood pressure during a normal pregnancy. The factor or factors that initiate the gestational renal vasodilatation (and plasma volume expansion) are maternal, not fetoplacental in origin. Apart from ruling out prostaglandins as an initiating agent, animal studies have not yet defined the precise nature of the initiating factors; it is unlikely that the gestational plasma volume expansion can be the sole cause of the increased GFR seen in pregnancy. The normal kidney in pregnancy exhibits substantial renal reserve to amino acid infusion, despite being already vasodilated by the gestational stimulus. The renal volume-sensing and control system of tubuloglomerular feedback is fully operative in pregnancy, and appears to be 'reset' to perceive the expanded plasma volume of pregnancy as normal. This observation agrees with many other indications that the sensors perceiving and controlling intravascular volume are reset during a normal pregnancy to enable the mother to accommodate the increased plasma volume without provoking a natriuretic response. Multiple pregnancies do not have any cumulative, long-term deleterious effects on renal function, either when the underlying function is normal or when it has been compromised by removal of renal mass plus high-protein feeding. In the short-term, pregnancy does not worsen kidney function when underlying glomerulonephritis is present. Therefore, the hyperfiltration of pregnancy does not appear to be a damaging entity, unlike other hyperfiltration states studied in the male rat. Still unknown is the mechanism by which pregnancy does worsen underlying glomerular disease in some women. The preliminary data in the rat, presented above, suggest that the exacerbating influence may be something other than the glomerular haemodynamic changes of pregnancy. PMID- 3330488 TI - Volume homeostasis in normal and hypertensive human pregnancy. AB - In this chapter are outlined the many factors involved in the regulation of sodium and volume homeostasis in normal human pregnancy and their interrelationships. New developments concerning the role of sodium/potassium ATPase, atrial natriuretic peptide, arginine vasopressin and angiotensin II as regulatory forces are outlined, together with a review of earlier work. Abnormalities found in women with, or destined for, PAH are described and their significance is discussed. PMID- 3330489 TI - Water metabolism and vasopressin secretion during pregnancy. PMID- 3330490 TI - Acute renal failure in pregnancy. AB - Acute renal failure has become a very rare complication of pregnancy. This results from the virtual disappearance of septic abortion ARF and from the improvement of prenatal care, including the prevention of volume contraction which is mainly due to uterine haemorrhage, early diagnosis, and treatment of other classic maternal complications such as pre-eclampsia and acute pyelonephritis. The incidence of BRCN has also been declining during the last decade. Acute fatty liver, a potentially fatal disease, is often complicated by ARF. Early recognition of this disorder with prompt termination of pregnancy and intensive supportive therapy can reduce fetal and maternal mortality rate. The syndrome of idiopathic postpartum renal failure is also associated with a high morbidity and mortality. Beyond supportive treatment including haemo- or peritoneal dialysis, the use of potent antihypertensive drugs to control blood pressure and blood transfusion if necessary, specific therapy as plasma infusion, plasma exchange and antiplatelet drugs may be of value. Both peritoneal dialysis and haemodialysis may be used in gravidas with ARF. Early 'prophylactic' dialysis should be applied to pregnant women. Careful monitoring of fluid balance and anticoagulation is necessary during dialysis. PMID- 3330491 TI - Urinary tract infections complicating pregnancy. AB - Urinary infections, with a spectrum from covert bacteriuria to severe pyelonephritis, commonly complicate pregnancy. Serious infections follow untreated silent bacteriuria in a fourth of cases, and routine screening can be justified in high-risk populations, particularly those from lower socioeconomic strata. Despite an initial salutary response to a number of antimicrobial regimens, covert bacteriuria recurs in one-third of treated women whose risk of pyelonephritis remains at 25%. Acute cystitis may be unrelated to these other infections and responds readily to a number of regimens; however, single-dose therapy is not recommended since early pyelonephritis can be mistaken for uncomplicated cystitis. Pyelonephritis is the most common severe bacterial infection complicating pregnancy. These women are frequently quite ill, and hospitalization is recommended. Since 85% to 90% respond within 48 hours to intravenous fluids and antimicrobials, continued fever and evidence of sepsis after two or three days should prompt a search for underlying obstruction. Perhaps 20% of women with severe pyelonephritis develop complications that include septic shock syndrome or its presumed variants. These latter include renal dysfunction, haemolysis and thrombocytopaenia, and pulmonary capillary injury. In most of these women, continued fluid and antimicrobial therapy result in a salutary outcome, but there is occasional maternal mortality. PMID- 3330492 TI - Nephrolithiasis and gestation. AB - Although both anatomical and physiological changes in pregnancy may predispose to kidney stone formation, it still remains an uncommon occurrence. Correct diagnosis is often difficult. Ultrasound has become the primary diagnostic tool, and a limited study excretory urogram is only necessary for complicated cases. Nephrolithiasis during pregnancy occurs more frequently during the later stages of gestation in multiparas, and without a difference in laterality. Conservative management with bed rest, hydration and analgesia can result in spontaneous passage of the majority of stones in gravidas. Past experience indicates that cystoscopy and/or surgery can usually be done safely when absolutely necessary. Pre-existing stone disease can increase the incidence of maternal urinary tract infections by 10-20%. The most common obstetric complication of stones during gestation is the precipitation of premature labour by renal colic. Unfortunately, most drugs used to treat stone disease are contraindicated in gestation. Experimental evidence suggests that known inhibitors of stone formation are present in gestation, and may help to explain why the incidence of stones is not increased in this particularly hypercalciuric state. PMID- 3330493 TI - Gestation in women with kidney disease: prognosis and management. AB - Physicians may be called upon to guide patients with renal disease on the advisability of conceiving or maintaining a gestation, or to manage pregnancies permitted to continue. The prevailing view is that the degree of functional impairment and the presence or absence of hypertension prior to conception determine both pregnancy outcome and the effect of gestation on the natural history of the kidney disorder (Table 4). Normotensive women with minimal dysfunction have a 90% chance of success and there is little evidence that gestation will adversely affect the disease. Presence of hypertension increases the complications rate substantially, and prognosis is also poorer in women with moderate renal dysfunction. Most gestations in the latter group succeed, but at considerable maternal risk: over 20% of these women experience renal functional deterioration, and 30-40% of them have major problems with hypertension. Thus we tend not to recommend pregnancy in patients with moderate renal insufficiency, and definitely discourage gestation when GFR is severely impaired. There are a number of diseases in which pregnancy should not be undertaken, including scleroderma and periarteritis. Some authors believe that women with membranoproliferative glomerulonephritis also do poorly, and opinions differ on the effects of gestation on IgA nephropathy, focal glomerulosclerosis, and reflux nephropathy. Table 5 summarizes our view concerning pregnancy in a number of specific renal disorders. Finally, in addition to the controversies noted above, there are other unresolved problems requiring further study. For instance, protein restriction should be avoided until the effect of this therapeutic manoeuvre on fetal development is evaluated. Also needed are conclusive studies on whether or not the physiological hyperfiltration of human pregnancy affects adversely pre-existing renal disease. PMID- 3330494 TI - Managing diabetic patients with nephropathy and other vascular complications. AB - Since the metabolic changes in normal pregnancy are diabetogenic, pregnancy imposes a severe stress on the metabolic milieu of diabetic patients. Moreover, many patients with long-standing diabetes have vascular complications, including retinopathy, renal insufficiency, nephrotic syndrome and hypertension, that represent separate risk factors for optimal fetal development. Recent experience has suggested that maternal hyperglycaemia, and associated fetal hyperinsulinaemia, may represent an important factor in the development of fetal complications. During the past two to three decades the incidence of perinatal deaths has been reduced in all cases of diabetics to a level that approaches the rate in healthy gravidas when severe congenital anomalies are excluded. Fetal and neonatal morbidity have also been reduced, although rates of congenital anomalies, polyhydramnios and respiratory distress syndrome remain high. In patients with significant vascular complications, especially nephropathy and retinopathy, there is no evidence that pregnancy alters the natural course of these complications. Although the morbidity associated with oedema formation and hypertension is elevated, with meticulous management of patients with diabetic nephropathy, especially in the absence of severe renal insufficiency and/or severe hypertension, pregnancy performance and outcome can be similar to other insulin-dependent diabetics. PMID- 3330495 TI - Reflux nephropathy and pregnancy. AB - Reflux nephropathy is one of the most frequent renal diseases encountered in women of childbearing age. Patients with severe bilateral atrophy are the most likely to develop proteinuria, hypertension, focal glomerular sclerosis and progressive chronic renal failure, and those with persistent vesicoureteral reflux are the most likely to suffer recurrent pyelonephritic episodes. Often the disease is clinically latent and first manifests itself in pregnancy, mainly by urinary tract infection but also by proteinuria, hypertension, pre-eclampsia or renal failure. Pregnancy is most often successful and uneventful whenever renal function is normal or near normal and hypertension is absent at conception. Urinary tract infection accounts for frequent morbidity but rarely results in fetal mortality. By contrast, when renal function is significantly impaired, that is in patients whose plasma creatinine concentration is in excess of 0.18-0.20 mmol/l at conception, especially when hypertension is also present, there is clearly a high risk of severe fetal growth retardation or intrauterine death. Moreover, there is a striking risk of rapid worsening of renal function and hypertension, with accelerated progression towards end-stage renal failure. Thus, women with reflux nephropathy should attempt to conceive before the plasma creatinine concentration has reached 0.18 mmol/l, and patients with values higher than these should be clearly advised of the high risk for both the pregnancy and the progression of the disease. PMID- 3330496 TI - Renal pathology in pre-eclampsia. AB - Pre-eclampsia affects the kidney both functionally and morphologically. Renal haemodynamics decrease and urinary protein excretion increases, in part due to lesions affecting the glomerulus, where a combination of changes produces a characteristic appearance and permits differentiation of pre-eclamptic nephropathy from other glomerular alterations associated with hypertension in pregnancy. In pre-eclampsia the glomerulus is diffusely enlarged and bloodless, due not to proliferation, but to hypertrophy of the intracapillary cells. These alterations, best described ultrastructurally, include hypertrophy of the cytoplasmic organelles in endothelial and occasionally mesangial cells, particularly the lysosomes, which undergo marked enlargement and vacuolization (due to accumulation of free neutral lipids). These reactive changes have been termed 'glomerular capillary endotheliosis'. Other lesions, observed occasionally, include subendothelial and mesangial electron-dense deposits, as well as interposition of mesangial cell cytoplasm or mesangial matrix along an otherwise normal basement membrane. Some investigators have described immunohistologic findings (presence of IgM, IgG and fibrin) which they believe specific for pre-eclampsia, and others have claimed the disease may cause focal segmental glomerulosclerosis (FSGS). We believe the immunohistologic findings are non-specific and insudative, and that FSGS when present predates the pre eclamptic complication. Finally, the renal lesions appear fully reversible and the disease has no remote cardiorenal effects on its patients. PMID- 3330497 TI - Reproductive endocrinology in uraemia. PMID- 3330498 TI - Alberto Monroy 1913-1986. PMID- 3330499 TI - Mammalian development futures, 1987. PMID- 3330500 TI - Recent advances in mammalian development. Dedicated to the memory of Alberto Monroy. PMID- 3330502 TI - Cellular interactions of mouse fetal germ cells in in vitro systems. PMID- 3330501 TI - Cell lineage analysis in mammalian embryogenesis. PMID- 3330503 TI - Testis determination and the H-Y hypothesis. PMID- 3330504 TI - Cell heterogeneity in the myogenic lineage. PMID- 3330505 TI - Immunological aspects of implantation and fetal survival: the central role of trophoblast. PMID- 3330506 TI - Cytoskeletal alterations and nuclear architectural changes during mammalian fertilization. PMID- 3330507 TI - Developmental potency of gametic and embryonic genomes revealed by nuclear transfer. PMID- 3330508 TI - Ovum factor and early pregnancy factor. PMID- 3330510 TI - [Evaluation of the immunoperoxidase technic in renal biopsy examination]. PMID- 3330509 TI - Development of the human preimplantation embryo in vitro. PMID- 3330511 TI - [Cytological examination of skin lesions--a method for the diagnosis of hematopoietic tumors]. PMID- 3330513 TI - The influence of nitrite on sulfonamide drug metabolism in animals. PMID- 3330512 TI - The emergence of Lyme disease in a changing environment in North America and central Europe. AB - Lyme disease has recently begun to emerge as a significant threat to human health, both in Europe and the United States. Late sequellae, resembling those of neurosyphilis and multiple sclerosis, may occur many years after initial infection. Spontaneous abortion accompanies arthritis, carditis and neuritis as burdensome short-term sequellae. Thousands of new infections are recognized each year on each side of the Atlantic, although reporting may be incomplete. The disease was described in Europe nearly a century ago and named erythema chronicum migrans, but its etiology has only recently been defined. The name "Lyme disease" was coined to describe a particularly intense American focus of disease, but the term has gained wide acceptance on both continents. The identity of the American and European etiological agents involved has yet to be determined. In America, a deer-associated, often bird-transported tick transmits this mouse-reservoired spirochete. The European situation seems more complex because the vector tick feeds on a greater variety of vertebrates. The reservoir hosts of the spirochete have yet to be determined. The role of Ixodes ricinus and possible other vectors in perpetuating transmission of the European infection remains to be defined. Whether I. ricinus as well as I. dammini merely serve as a bridge to the human population or are important for the maintenance of the feral cycle remains to be seen. The capacity of a tick to maintain transmission of Lyme disease spirochetes depends upon a complex set of properties, including competence as a host for the spirochete, a pattern of feeding that focuses on a particular reservoir favored by a pattern of tick activity, during each transmission season, in which nymphs feed before larvae. Transmission would be favored by an environment, such as that of islands, in which the variety of potential reservoir hosts is restricted. Hosts, for example reptiles, that might fail to support growth of the spirochete would serve to dilute effective transmission in nature. Similarly, the capacity of a vertebrate to maintain the infection requires long-term support of the spirochete in a tissue site accessible to vector ticks, tolerance of repeated feeding by vector ticks and a pattern of host activity that exposes the host to numerous bites. The intensity of infection depends upon a continuous pattern of transmission in which each generation is infected anew. The rare event in which the vector inherits infection would serve mainly to transport the spirochete to a new site, most effectively by migrating birds.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3330515 TI - Comparative metabolism of lincomycin in the swine, chicken, and rat. PMID- 3330514 TI - Metabolism and residue studies with actaplanin. PMID- 3330516 TI - The metabolism and fate of closantel (Flukiver) in sheep and cattle. AB - Closantel was reasonably well absorbed in sheep and cattle. After oral (10 mg/kg) or parenteral (5 mg/kg) administration, similar peak times (8-48 h) and peak plasma levels (45-55 micrograms/mL) are observed. Plasma level-time curves are superimposable for either route and increase linearly with the dose. The elimination half-life of closantel is 2 to 3 weeks. The relative bioavailability of 50% of oral closantel can partly be explained by incomplete absorption. Experiments in sheep with 14C-closantel revealed that the plasma radioactivity is almost exclusively due to the unmetabolized drug, metabolites accounting for less than 2%. At least 80% of the dose was excreted with the feces over the investigational period of 8 weeks, and less than 0.5% with the urine. Closantel was only poorly metabolized. Over 90% of the fecal radioactivity was due to the parent compound. Two monoiodoclosantel isomers were the only fecal metabolites detected with radio-HPLC. The distribution of closantel to tissues was limited by its high protein binding. Closantel bound strongly (greater than 99.9%) and almost exclusively to plasma albumin. Accordingly, tissue concentrations were many times lower than the corresponding plasma levels. Residual radioactivity in sheep in all tissues but liver was entirely due to closantel. About 30% to 40% of the liver radioactivity could be attributed to monoiodoclosantel. In both sheep and cattle, residual tissue concentrations decline parallel to the plasma concentrations. Consequently, the plasma kinetics of closantel reliably reflect its depletion from tissues. Independently of the dosing scheme and route of administration, the maximum daily intake by the consumer was always below the acceptable daily intake within 4 weeks after the last dose. PMID- 3330518 TI - Comparative in vivo and in vitro metabolism of ivermectin in steers, sheep, swine, and rat. PMID- 3330517 TI - The in vitro and in vivo metabolism of morantel in cattle and toxicology species. PMID- 3330519 TI - Metabolism of the synthetic prostaglandin alfaprostol in cows, pigs, and rats. PMID- 3330520 TI - Structure-activity relationships in the threshold assessment. PMID- 3330521 TI - Comparative metabolism in food-producing animals: programs sponsored by the Center for Veterinary Medicine. PMID- 3330523 TI - Heart rate reduction, a new and old therapeutic principle? PMID- 3330522 TI - Tissue drug residues and their toxicological significance. PMID- 3330524 TI - Alinidine in heart patients: electrophysiologic and antianginal actions. AB - The electrophysiological properties of alinidine were studied in 18 patients. Four of these patients were pretreated with intravenous propranolol, 0.2 mg kg-1, and atropine, 0.04 mg kg-1, to induce autonomic blockade. Alinidine produces a sustained bradycardiac effect at a dose of 40 mg intravenously. The sinus node recovery time increased in patients with and without autonomic blockade, while the corrected sinus node recovery time was unaffected by alinidine in patients without autonomic blockade and increased in patients with autonomic blockade. The effective refractory period of the right atrium, the atrioventricular node and the right ventricle, as well as the functional refractory period of the atrioventricular node, were unaffected by alinidine in both groups of patients. Intraatrial, atrioventricular and intraventricular conduction was also not altered by this drug. Thus the electrophysiological profile of alinidine differs from other bradycardia-inducing agents such as beta-blockers or calcium antagonists. Furthermore we evaluated alinidine efficacy in 14 patients with angiographically proven coronary artery disease and stable angina during a 10 week placebo-controlled randomized double-blind trial. Alinidine (40 mg three times a day) reduced the number of anginal attacks and the average number of nitroglycerine capsules consumed. The double product was slightly lowered during rest but more pronounced during exercise. This effect was mainly due to decreased heart rate. The ischaemic ST-segment depression was diminished. Exercise tolerance was clearly improved in 6, slightly improved in 2, and unchanged in 4 patients. PMID- 3330525 TI - A summary of the acute effects of falipamil in man. AB - The verapamil analog falipamil is a new compound with specific bradycardic action on the sinus node. It differs from verapamil with respect to its electrophysiological and haemodynamic actions. Falipamil causes a slight prolongation of intraatrial and intraventricular conduction, whereas sinuatrial and AV-node conduction is enhanced. The refractory periods of atrial and ventricular myocardium and ventricular repolarization are significantly prolonged, whereas the refractory period of the AV-node is shortened. Falipamil fails to influence any haemodynamic parameter significantly at rest, if heart rate is kept constant. In exercise-induced myocardial ischaemia, changes in haemodynamics reflect changes in heart rate. Increased sinus rate at rest is significantly reduced by falipamil 15%-25%. Around 150 mg falipamil prove aequieffective to about 40 micrograms pindolol. Atropine-induced and catecholamine-induced sinus tachycardia is also significantly diminished. Increased sinus rate during exercise is lowered by about 10%. Through reduction of heart rate, falipamil proves capable of significantly diminishing or even preventing ischaemic ST-segment depression and ischaemia induced increase in pulmonary capillary pressure. Thus falipamil can be used to normalize sinus rate in patients with sinus tachycardia of various origin, particularly in intensive care, in acute ischaemic heart disease, in anaesthesia and in surgery cases. PMID- 3330526 TI - Comparison of AQ-A 39 with propanolol and placebo in ischaemic heart disease. AB - In a randomized, controlled study 10 male patients with angiographically confirmed ischaemic heart disease received AQ-A 39 (falipamil), a heart rate reducing agent in a single intravenous dose (2 mg kg-1) in comparison to propranolol (0.1 mg kg-1). Both drugs reduced heart rate in supine position slightly. The rise of heart rate induced by orthostasis was diminished by AQ-A 39 to 4 +/- 2 beats min-1 and by propranolol 9 +/- 2 beats min-1. After submaximal exercise heart rate during placebo was 129 +/- 3, during AQ-A 39 113 +/- 3 and during propranolol 103 +/- beats min-1. Systolic arterial pressure decreased by propranolol only. The double product obtained by placebo was 231 +/- 10 while it was for 194 +/- 9 after AQ-A 39 and 158 +/- 6 mmHg min-1 after propranolol, respectively. Both substances increased exercise time as compared to placebo. Furthermore, AQ-A 39 increased noradrenaline plasma levels in the upright position and after submaximal exercise compared to the values obtained following placebo. The dose of isoproterenol necessary to induce an increase of heart rate by 20 beats min-1 was after AQ-A 39 4.2 times greater and following propranolol 9.2 times greater than during placebo. The results suggest that AQ-A 39 will be useful in the short term management of patients with ischaemic heart disease. PMID- 3330527 TI - ST 567 (alinidine) in stable angina: a comparison with metoprolol. AB - Alinidine, a drug which reduces heart rate without depressing myocardial function was compared against metoprolol, a beta-blocking drug, in the treatment of stable angina pectoris in a double-blind cross-over trial. It was found that both drugs reduced anginal attacks and nitroglycerine consumption to a comparable degree. Exercise tolerance did not appear to be improved by either drug yet chest pain at ergometry was postponed by both drugs. In the doses used metoprolol was more effective in restraining heart rate, both at rest and even more during exertion. Both drugs were well tolerated and side-effects were few. It seems probable that the optimal dose of alinidine was not used in this trial and that the dosage could have been higher. PMID- 3330528 TI - ST 567 compared with propranolol in stable angina. AB - The aim of this study was to investigate the effectiveness of ST 567 in patients suffering from ischaemic heart disease and to compare the effects of this drug with those of propranolol. The study group consisted of 48 male patients, mean age 53, with stable, exercise-induced angina pectoris. After a two-week run-in placebo period, the patients were randomized to treatment with ST 567 3 X 30 mg (N = 24) and propranolol, 3 X 40 mg (N = 24). The drugs were administered in a double blind fashion during four weeks. Heart rate at rest was decreased by ST 567 from 76 to 65 (P less than 0.005) by propranolol from 76 to 62 (P less than 0.001). Systolic blood pressure was lowered by ST 567 from 131 to 121 (NS) and by propranolol from 133 to 118 (P less than 0.05). Exercise tolerance was increased by ST 567 from 20 X 10(3) to 34 X 10(3) J (P less than 0.05), by propranolol from 26 X 10(3) to 32 X 10(3) J (P less than 0.01) (mean values). Anginal attacks (no. per week) were reduced by ST 567 from 14 to 7 (P less than 0.05) and by propranolol from 14 to 5 (P less than 0.01). Nitroglycerin consumption in no. of tablets per week decreased in ST 567 from 12 to 7 (P less than 0.01), in propranolol from 11 to 4 (P less than 0.0). There were 7 drop outs during treatment with ST 567:2 cases of myocardial infarction, exacerbation of angina in 2 patients, visual disturbances in 2 patients, vertigo in 1 patient. With propranolol we observed worsening of angina in 1 patient, with disturbances in sexual potency in 1. IN CONCLUSION: ST 567 is an effective agent in chronic angina but slightly less effective than propranolol in the dosages studied. PMID- 3330529 TI - History of 'specific bradycardic agents'. PMID- 3330530 TI - New aspects of clinical drug resistance: the role of gene amplification and the reversal of resistance in drug refractory cancer. PMID- 3330531 TI - Control of gene expression and the replication and pathogenesis of retroviruses. AB - The replicative pathways, modes of transmission, and pathobiology of retroviruses depend upon an interplay between mechanisms that control host gene expression and the expression of virus gene products. The nonacute transforming viruses that contain only the gag, pol, and env genes are dependent upon host gene trans acting transcription factors for replication and expression. The host cell trans acting factors vary according to cell type. For this reason, the tissue tropism and pathogenesis of these viruses depend upon the compatibility of cis-acting viral regulatory elements with the host trans-acting factors. Such interactions play a dominant role in determining tissue-specific tumor induction of murine retroviruses. Recently a group of retroviruses that induce trans-acting regulatory factors has been identified. The group includes etiologic agents of ATLL and AIDS. Compatibility between the virally encoded trans-acting gene regulatory factors and cis-acting regulatory elements of differentiated cells may play the dominant role in determining the tissue specificity and pathogenic effect of these viruses. PMID- 3330533 TI - Adjuvant therapy in the treatment of osteosarcoma. PMID- 3330532 TI - The dysplastic nevus syndrome: precursors of hereditary and nonfamilial cutaneous melanoma. PMID- 3330535 TI - Vitamin A analogues in cancer chemoprevention. PMID- 3330534 TI - Epidemiologic patterns of colorectal cancer. PMID- 3330536 TI - Cancer imaging with monoclonal antibodies. PMID- 3330537 TI - Therapy of colorectal hepatic metastases. PMID- 3330538 TI - Unconventional fractionation schemes in radiotherapy. PMID- 3330539 TI - Bone marrow transplantation in the therapy of non-Hodgkin's lymphomas. PMID- 3330540 TI - Human oncogenes. PMID- 3330541 TI - Adoptive immunotherapy of cancer using lymphokine activated killer cells and recombinant interleukin-2. PMID- 3330542 TI - Chromosomal rearrangements, genes, and fragile sites in cancer: clinical and biologic implications. PMID- 3330543 TI - Spirometry--a comparison of the best test, the mean test and the maximal test. PMID- 3330544 TI - Evaluation of Plasmodium falciparum-microsomal in vitro system for testing pro drugs. PMID- 3330545 TI - Effect of protein malnutrition on insulin secretion. PMID- 3330546 TI - Fatigue fracture of the tibia in dancers (report of 3 cases). AB - The authors report 3 cases of fatigue fractures of the tibia in dancers studying at the same school. They emphasize several aetiopathogenetic aspects of the problem and review the literature. PMID- 3330547 TI - Vertebral fusion dynamics in the thoracic and lumbar spine induced by allogenic demineralized bone matrix combined with autogenous bone marrow. An experimental study in rabbits. AB - The aim of this study was to examine the capability of grafts consisting of demineralized bone matrix combined with autogenous bone marrow to enhance fusion in the thoracic and lumbar spines in rabbits. Thirteen rabbits were operated on, using a posterior approach. A combined intertransverse and interspinous fusion was performed. Fusion was achieved first in the lumbar segments, then in the thoraco-lumbar segments and lastly in the thoracic segments. The best results were achieved in the lumbar spine, where complete fusion occurred in 83%. The combination of demineralized bone matrix and autogenous bone marrow proved to be a reliable transplant material for experimental spinal fusion. PMID- 3330548 TI - Ultrasonography in pathological conditions of muscles, tendons and joints. AB - The authors discuss the use of ultrasonography in the investigation of pathological condtions of muscles, tendons and joints. The indications and related ultrasonographic findings are presented. The importance of this method is emphasized both as an aid to diagnosis and choice of treatment. Its use in evaluating the effectiveness of treatment is also discussed. PMID- 3330549 TI - Monostotic fibrous dysplasia of the spine: case report. AB - A case of monostotic fibrous dysplasia of the spine is presented. It was referred to us after a history of 3 years' pain. The site of the anomaly is so exceptional that it invited comparison with the six other cases described in the literature. This comparison produced resemblances which differentiate this particular type of monostotic fibrous dysplasia form that located at other sites, both in its clinical aspects and its radiographic appearances. PMID- 3330551 TI - [The clinical use of nonresorbable hydroxylapatite for alveolar ridge augmentation with or without autogenous cancellous bone]. PMID- 3330550 TI - [Experimental study of bone deficits' healing in animals, following their filling with gluing fibrous substance and heterologous collagen]. PMID- 3330552 TI - The bacteriological examination of slit-skin smears in leprosy control programmes using multiple drug therapy: a plea for radical changes in current operational methodology. PMID- 3330554 TI - The simultaneous inoculation of Mycobacterium leprae and M. intracellulare into nude mice: development of cutaneous leproma and accelleration of foot pad swelling. AB - Organisms of the non-pathogenic Mycobacterium intracellulare serotype 19 Darden enhanced the pathogenicity of M. leprae when inoculated together into the foot pads of nude mice. This supporting effect could be demonstrated by an accelleration of foot pad swelling, beginning 4 months after inoculation and by the development of cutaneous leproma on dorsal and lateral body sites within 6 months after inoculation. These leproma increased in number and size during the 9 months they were under observation and demonstrated micromorphological characteristics similar to those of human leprosy. PMID- 3330553 TI - Renal involvement in Mycobacterium leprae infected mice. Histopathological, bacteriological and immunofluorescence study. AB - Swiss albino mice were inoculated in the footpads with Mycobacterium leprae obtained from untreated lepromatous patient. The kidneys obtained from the animals sacrificed during different periods were processed for histopathology, presence of AFB and immunofluorescence studies. Renal lesions, AFB and immune complex deposits were seen in the infected animals. Such findings have not been studied in great detail in experimental leprosy earlier. PMID- 3330555 TI - Role of immune complexes in alteration of lymphocyte subpopulation numbers and functions in experimental leprosy. AB - Swiss albino mice (normal as well as thymectomised and irradiated were inoculated into the footpads with Mycobacterium leprae and divided into two main phases of study. Phase I comprised of animals not given preformed immune complexes (IC). Uninfected controls were however included. Phase II consisted of animals given in vitro prepared IC at zero day period (OdIC), three month period (3mIC) or six month period (6mIC) to both uninfected and infected groups. Splenic lymphocytes were isolated to quantify T and B cells and their responses to M. leprae antigen and four different mitogens. Significant decrease in T cell counts and blast transformation was seen in the M. leprae infected animals which were also administered with immune complexes. Immunosuppression by IC was therefore seen to be enhanced in the presence of M. leprae infection. PMID- 3330556 TI - Leprosaria numismatica: leprosarium money and related material. PMID- 3330559 TI - [An introduction to reproductive medicine and ethics]. PMID- 3330558 TI - [An overview of recent advances in reproductive medicine]. PMID- 3330557 TI - Immunohistochemical analysis of human lung cancers with anti-ras p21 monoclonal antibodies. AB - The expression of ras oncogene product p21 in human malignant pleurisy and primary lung cancer was studied immunocyto-histochemically with monoclonal antibodies (MoAbs) rp-28 and rp-35 against ras p21. In pleural effusion cells, cancer cells revealed more intensively positive reaction with MoAb rp-35 than with MoAb rp-28, especially in the plasma membrane, and no positive reaction was obtained in any kind of inflammation cells with the exception of faintly positive reaction in the cytoplasm of macrophages. In primary lung cancers, well or moderately differentiated adenocarcinoma tissues showed higher reactivity with MoAb rp-28 than those of poorly differentiated adenocarcinoma or any other histological subtype of lung cancer. With MoAb rp-35, intensively positive reaction was obtained in most of cases with all different histological subtypes of lung cancer. The staining in cancer cells was usually localized intensively to the plasma membrane and weakly to the cytoplasm with both MoAbs. Normal bronchial epithelial and glandular tissues showed only cytoplasmic staining. These two MoAbs, especially MoAb rp-35, may be useful in clinicopathological applications for the diagnosis of malignant pleurisy and primary lung cancer. PMID- 3330560 TI - AI/LEARN: an interactive videodisk system for teaching medical concepts and reasoning. AB - This paper describes AI/LEARN, an educational videodisk system designed to teach clinical observational skills and reasoning in medicine. The AI/LEARN system uses a learning conditions approach to teaching. To teach visual concepts, we use the principle of exemplar/nonexemplar pairs and immediate feedback. To teach If-Then problem solving we use the format of minicases with delayed feedback. The software to operate the system has been custom developed and is domain independent. The result is a prototype of a new authoring package for videodisk teaching which operates on IBM compatible microcomputers. The medical domain selected for this prototype system was rheumatic diseases; the knowledge used to teach reasoning skills is derived from the knowledge base of an expert system: AI/RHEUM. PMID- 3330561 TI - Inhibition of mutagenicity by glycyrrhiza extract and glycyrrhizin. AB - The effects of Glycyrrhiza extract and one of its components, glycyrrhizin, on the mutagenicities of several mutagens were investigated by means of a modification of the Ames' test. Both inhibited the mutagenicities of 3-amino-1,4 dimethyl-5 H-pyrido[4,3-b]-indole (Trp-P-1) and 3-amino-1-methyl-5 H-pyrido[4,3 b]indole. Since the Glycyrrhiza extract and glycyrrhizin inhibited the mutagenicity of activated Trp-P-1, it was clear that their inhibitory effects were not due to inhibition of the enzyme activity of the S9 fraction. Both Glycyrrhiza extract and glycyrrhizin also inhibited the mutagenicities of benzo[a]pyrene, 3-methylcholanthrene, 2-naphthylamine, 2-amino-6 methyldipyrido[1,2-a:3',2'-d]-imidazole, dimethylnitrosoamine and dimethylaminoazobenzene. The mutagenicity of 2-(2-furyl)-3-(5-nitro-2 furyl)acrylamide (AF-2) was inhibited by the Glycyrrhiza extract but not by glycyrrhizin. This suggested that a component different from glycyrrhizin, present in the Glycyrrhiza extract, inhibited the mutagenicity of AF-2. PMID- 3330562 TI - Specific inhibitors for prolyl endopeptidase and their anti-amnesic effect. AB - Several peptides and peptide derivatives were tested for their inhibitory effect on prolyl endopeptidase and possible properties as anti-amnesic agents. Among the compounds tested, Z-Gly-Pro-CH2Cl, Z-Val-prolinal, Boc-Pro-prolinal, Z-Pro prolinal, aniracetam and pramiracetam inhibited the enzyme activities at Ki values in the order of nM to microM, and the effect of the prolinal-containing peptide derivatives was specific for prolyl endopeptidase. Z-Pro-prolinal was the most effective inhibitor in vitro (Ki = 5 nM) and in vivo (50 to 70% inhibition in various organs of rat at a dose of 1 mumol/animal i.p.). Regional differences were observed in the effect of inhibitors on the brain enzyme activities: most active in mesencephalon, followed by striatum, cerebellum, hippocampus, hypothalamus; and inactive in cerebral cortex and medulla oblongata. In the passive avoidance learning test using rats, pretreatment with Z-Pro-prolinal prevented the induction of amnesia by scopolamine at the dose of 1 mumol/animal, i.p. Z-Val-prolinal, Z-Pyr-prolinal and Z-Gly-Pro-CH2Cl were also effective in the retention test at 24 and 48 h after the training trial. The antiamnesic effect of these compounds was approximately parallel to the in vitro inhibitory activities on prolyl endopeptidase. These results suggest the possibility that the inhibitors exhibit their anti-amnesic effect through the regulation of the enzyme activity in the brain. PMID- 3330563 TI - [The Langerhans cell: an immunological role for the gingival epithelium]. PMID- 3330564 TI - [Scoring for cerebrospinal fluid inflammatory cells: using sedimentation method]. PMID- 3330565 TI - [Preliminary survey of mutagenic substances in environmental pollutants from the southern Taiwan]. PMID- 3330566 TI - [Recent progress in the discovery and development of plant antitumor agents]. PMID- 3330567 TI - [In vitro granulomonopoiesis of bone marrow cells and their response to granulomonopoietic enhancing activity in patients with hematologic disorders]. PMID- 3330568 TI - [Prognostic analysis of malignant obstructive jaundice after biliary decompression]. PMID- 3330569 TI - [Echo levels of urinary stones and effects of extracorporeal shock wave lithotripsy]. PMID- 3330570 TI - [Adrenal hemangioma: a case report]. PMID- 3330571 TI - [Spermatocytic seminoma. Case report and review of the literature]. PMID- 3330572 TI - Jules Francois: a life for ophthalmology (1907-1984). PMID- 3330573 TI - Echography of optic disc related pathology in diabetic retinopathy. AB - Combined A- and B-scan examination of eyes with diabetic retinopathy and opaque media provides information about the presence and density of vitreous hemorrhages, can detect membranes inserting into the optic disc or the retina and differentiate them from retinal detachment. Absolute and relative indications for echographic examination are listed and some echograms concerning vitreous hemorrhage, proliferating membranes and traction retinal detachment are presented. The value of both A-scan standardized echography and contact B-scan technique for previtrectomy evaluation is stressed. PMID- 3330575 TI - [The origin of uremia]. PMID- 3330574 TI - Cost sharing and the changing pattern of employer-sponsored health benefits. AB - The perception that employers have been redesigning group health benefits to encourage more cost-effective use is distorted by limited study methods. New estimates of initiatives undertaken by larger private-sector employers--based on nationally representative data from the U.S. Bureau of Labor Statistics--reveal a more uncertain picture of cost containment. Cost sharing for initial hospital stays was broadened between 1981 and 1985, but coverage in most other areas- categories of care, lifetime benefit limits, etc.--was actually increased. Real health care expenditures will continue to grow absent more significant employee cost sharing. PMID- 3330576 TI - Role of endogenous adenosine as a modulator of the renin response to salt restriction. AB - Numerous studies indicate that exogenous adenosine can inhibit renin release. However, the hypothesis that endogenous adenosine functions to restrain the renin response to physiological and/or pharmacological stimuli remains untested. To address this hypothesis, we examined the effects of a novel adenosine receptor antagonist, 1,3-dipropyl-8-para-sulfophenylxanthine (DPSPX), on renin release in rats on a normal versus a low salt diet. DPSPX did not affect renal blood flow, glomerular filtration rate, filtration fraction, urine volume, or sodium excretion in rats on either a normal or low salt diet. In contrast, in rats on a low salt diet, DPSPX significantly increased arterial and renal venous plasma renin activity and the gradient of plasma renin activity across the kidney. DPSPX did not alter these indices of renin release in rats on a normal salt diet. These data support the hypothesis that endogenous adenosine functions to restrain the renin response to salt depletion. Finally, if these findings are applicable to man, caffeine consumption could account for the variable antihypertensive effect of a low salt diet. PMID- 3330577 TI - [Functions and metabolism of polynuclear neutrophils in patients under chronic hemodialysis]. AB - Clinical evidence indicates that infection is still a cause of morbidity and mortality in patients undergoing hemodialysis. The major role played by the polymorphonuclear cells in antimicrobial response by the host explained considerable study of several aspects of granulocyte functions in chronic hemodialysis patients. It is now well documented that hemodialysis induces the sequential activation of the complement components of the alternative pathway and may provide a mechanism for initiating leukoaggregation and sequestration of granulocytes. This complement activation could also explain the profound leukopenia observed shortly after the initiation of hemodialysis. It has been also assumed that the sequestration of granulocytes is dependent on a temporarily altered cell function and leads to a depressed chemotaxis, an impairment of phagocytic and bactericidal capacities. Moreover, a significant defect in the oxidative metabolism was observed before and during the course of the dialysis session. This article summarizes research that has been done on the function of neutrophils from chronic hemodialysis patients. PMID- 3330578 TI - [Epidemiology of terminal renal insufficiency treated by dialysis and therapeutic options in a population of 400,000 inhabitants (1975-1986)]. AB - Since January, 1, 1976, epidemiologic study of renal diseases has been leading in a French rural area of 400,000 inhabitants located in north coast of Britanny. Annual incidence of end stage renal failure (ESRF) treated by dialysis increased of 25% when two consecutive periods of five years each were compared: A (1976 1980) 46 per 10(6) inhabitants, B (1981-1985) 62 per 10(6) inhabitants. In 1986, the progression was confirmed: 96 per 10(6). At the time of the beginning of dialysis treatment, mean age (+/- SD) was not different between two periods: 53 +/- 17 yrs (A) vs 51 +/- 17 yrs (B) but it increased in 1986: 61 +/- 14 yrs. Sex ratio (M/F) progressed from 1 (A) to 1.75 (B). The study of causes of ESRF showed a net increase of secondary renal diseases (diabetes, amyloidosis), interstitial nephropathies due to obstructive uropathy (lithiasis) and drugs. For the period B, 91% of primary glomerulonephritis reaching ESRF had had renal biopsy. Idiopathic IgA nephropathy was the first cause of ESRF (13.7%, 0.85 pts/100,000) before diabetes (12%, 0.75/100,000), Polycystic disease (11.3%, 0.70/100,000), reflux nephropathy (9.6%, 0.60/100,000), focal and segmental glomerulosclerosis (8.8%, 055/100,000). Prevalence of ESRF for primary glomerulonephritis was calculated to 20.6% and according to the histological type to 28.3% for idiopathic IgA nephropathy, 34.8% for local and segmental glomerulosclerosis, 40% for idiopathic crescentic glomerulonephritis and only 6.6% for membraneous nephropathy. In the studied area, 58% of patients were treated out of hospital (at home or in self-dialysis units) whose 46% by hemodialysis and 12% by CAPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3330579 TI - [What does circulating beta 2 microglobulin signify in uremic patients on maintenance dialysis?]. AB - The authors report a 2 years prospective study on s beta 2M variations observed in a large uremic population (237 patients, 159 M, 78 F, age: 51.1 +/- 5.9 y.o.). The study consisted in two parts. A long term follow-up of s beta 2M in patients regularly treated with various dialysis modalities; hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), intermittent peritoneal dialysis (IPD) and continuous ambulatory peritoneal dialysis (CAPD). s beta 2M was found elevated in the overall population (41.4 +/- 10.2 mg/l) with a 12.5% variation over time observation in stable patients, not influenced by sex, causal nephropathy, and dialysis mode in anuric patients, beta 2M was inversely correlated with residual diuresis. Residual kidney function preserved longer and in a higher proportion of PD patients was the only significant fact explaining for the difference observed in s beta 2M levels between HD (46 +/- 5) and PD (33 +/- 3) patients. Intercurrent inflammatory and tumoral states increased significantly s beta 2M level in uremic patients. The short term study showed that highly permeable membranes (AN69, polysulphone) used either in HD, HF or HDF were able to decrease s beta 2M from 50 to 60%, and to remove 150 to 200 mg per session, while on the opposite HD/cuprophane increased s beta 2M from 10 to 15%. beta 2M dialysate/plasma equilibrium ratio for peritoneal membrane after a 6 hour dwelling time was 0.20, permitting a net removal of 45 +/- 4 mg/24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3330580 TI - Markers of insulin dependent diabetes mellitus. PMID- 3330581 TI - Arrhythmias and Guillain-Barre syndrome. AB - We report two patients with severe Guillain-Barre syndrome who had serious cardiac arrhythmias. One patient died of asystolic cardiac arrest; the other patient survived with conservative management. The association between the syndrome and arrhythmias, and the difficulties in the management of the latter, are reviewed. PMID- 3330582 TI - Steroid-responsive nephrotic syndrome due to minimal change nephropathy occurring while on captopril. PMID- 3330583 TI - Treatment of Salmonella typhimurium infection in a renal transplant patient with ciprofloxacin. PMID- 3330585 TI - Fenbufen trial in general practice. PMID- 3330586 TI - Disopyramide-induced hypoglycaemia and increased serum insulin. AB - A patient treated with disopyramide presented with hypoglycaemia, a raised serum insulin level and died of pneumonia. From these findings and a review of 10 case reports, we propose that disopyramide causes hypoglycaemia by stimulation of insulin release as described for the antimalarial drugs quinine and quinidine. PMID- 3330587 TI - Reflux nephropathy: 1987. PMID- 3330584 TI - Resistance of urinary tract isolates of Escherichia coli to cotrimoxazole, sulphonamide, trimethoprim and ampicillin: an 11-year survey. AB - The susceptibility of urinary tract Escherichia coli isolates to cotrimoxazole, sulphonamide, trimethoprim, and ampicillin was monitored over an 11-year period. A trend in increasing resistance to cotrimoxazole and trimethoprim was observed, but there was no comparable alteration in sulphonamide resistance. Ampicillin resistance was high at the beginning of the survey period and continued to rise. PMID- 3330588 TI - Art, observables, philosophy and the Otago Medical School. PMID- 3330589 TI - Chief health officer. PMID- 3330590 TI - Fatal strongyloidiasis in a renal transplant patient. PMID- 3330591 TI - Blister beetle dermatosis in New Zealand. AB - Seventy-four New Zealand Army personnel with a distinctive bullous dermatosis caused by an endemic beetle are described. These are the first reported cases of this condition in New Zealand. The beetle, Thelyphassa lineata (Fabricius) belonging to the family Oedemeridae was shown to be a vesicant species, as skin contact induced blisters in volunteers. This is a previously unrecognised property of this species. PMID- 3330592 TI - Autosomal dominant polycystic kidney disease diagnosed in utero using ultrasonography. PMID- 3330593 TI - Double blind, randomised trial comparing single dose enoxacin and trimethoprim for treatment of bacterial cystitis. AB - Women with acute lower urinary tract symptoms were enrolled in a randomised, double blind study and received either a single 400 mg dose of enoxacin or a single 600 mg dose of trimethoprim. Twenty of 29 women with bacterial cystitis were cured with enoxacin and 22 of 26 with trimethoprim. Both drugs were highly effective for the treatment of Escherichia coli, but enoxacin was disappointing for the eradication of Staphylococcus saprophyticus. Side effects were minimal. Single dose therapy is recommended as the treatment of choice for bacterial cystitis in general practice. PMID- 3330594 TI - The New Zealand Medical Journal 1887-1987. PMID- 3330596 TI - The New Zealand Medical Journal 1900 and since. PMID- 3330595 TI - The early years of the New Zealand Medical Journal, 1887-1896. PMID- 3330597 TI - Blister beetle dermatosis. PMID- 3330598 TI - Ultrasound and ovulation. AB - Diagnostic ultrasound may be used to both investigate unexplained infertility and monitor all types of infertility treatment in women. Presented in this paper are the numbers of cycles scanned and the numbers of scans performed over the period from November 1981 to March 1986. In patients with unexplained infertility there was only a 39% rate of normality observed with ultrasound. Ultrasound observation of ovulation in patients on clomiphene or gonadotrophin therapy showed a disappointingly low rate. PMID- 3330599 TI - Ileal infarction: a rare cause of tetanus in the elderly. AB - We report the case of a 70 year-old woman who presented with clinical tetanus following a four day history of abdominal pain and vomiting. The source of Clostridium tetani was an infarcted loop of ileum resulting from pelvic adhesions. The treatment of tetanus and the incidence of endogenous sources of Clostridium tetani are reviewed. Health Department figures for the decade 1973 1982 show that 70% of reported cases of clinical tetanus occur in those aged 45 years or older. PMID- 3330600 TI - Arrhythmias during concurrent therapy with captopril and frusemide. PMID- 3330601 TI - Once-nightly treatment with pirenzepine or cimetidine for peptic ulcers: a multicentre, randomised, double blind, controlled study. AB - Sixty-nine patients with symptomatic and endoscopically diagnosed gastric or duodenal ulcers received treatment with either pirenzepine 100 mg or cimetidine 800 mg one hour before bedtime in a prospective randomised, double blind study. Fifty-five patients completed the six weeks treatment period of whom 13/15 (87%) gastric ulcers and 13/16 (81%) duodenal ulcers, healed with pirenzepine compared to 8/11 (73%) gastric ulcers and 10/13 (77%) duodenal ulcers treated with cimetidine for the same period. The differences in healing rates between pirenzepine and cimetidine were not statistically significant. Pirenzepine 100 mg administered at night is therefore an effective treatment for gastric and duodenal ulcers. PMID- 3330603 TI - Heart transplantation: excellent therapy for the carefully selected patient. PMID- 3330602 TI - Transdermal clonidine (Catapres-TTS) monotherapy in the management of mild hypertension in general practice. AB - The efficacy and patient acceptance of transdermal clonidine applied once a week were assessed in 62 mild hypertensives previously controlled on a diuretic and/or beta-blocker in a general practice setting involving 18 general practitioners. Patients underwent 3-5 week wash-out period and those patients whose mean seated diastolic blood pressure returned to levels between 91-105 mmHg or increased by greater than 10 mmHg above the initial value, were titrated with transdermal clonidine (Catapres-TTS-1, 2, or 3) and maintained on the optimal dose for 3 months with monthly check-ups. Satisfactory response of blood pressure to levels below 90 mmHg or greater than 10 mmHg reduction from the wash-out level was obtained in 85% of patients who completed the titration phase; nine patients failed to achieve a satisfactory blood pressure control. There was no significant difference in blood pressure response between previous therapy and transdermal clonidine treatment. Systemic side effects were minimal. Eight patients withdrew because of local allergic contact dermatitis. This study confirms that transdermal clonidine is at least as effective in reducing blood pressure as diuretic and/or beta-blocker therapy. PMID- 3330604 TI - Elmer McCollum and the disappearance of rickets. PMID- 3330605 TI - Automation in hematological cytology ou: les "machines" trop souvent "celibataires". PMID- 3330606 TI - [Cytogenetic course after allograft of bone marrow in chronic myeloid leukemia]. AB - Bone marrow karyotyping was serially performed in 23 Ph1+ chronic myelocytic leukemia patients treated with allogeneic bone marrow transplantation (BMT). Two patients underwent 2 BMT each. Fifteen patients had only normal karyotypes and 8 patients (after 10 BMT) had either sporadic Ph1+ metaphases (6 cases) or cytogenetic signs of relapse (4 cases, of which in 1 case, without hematological symptoms), or both in succession. Sporadic Ph1+ metaphases were found early after BMT (never after the 6th month). Although they were more frequent in non splenectomized patients than in others, there was no significant correlation between sporadic Ph1+ metaphases and disease features, treatment regimens or evolution after BMT. PMID- 3330608 TI - [The genome of HIV (HTLV-III, LAV), the human immunodeficiency virus]. PMID- 3330609 TI - [Genetic control of the stimulation of cell division]. PMID- 3330607 TI - [Acute lymphoblastic leukemia, Burkitt-cell type, after Hodgkin's disease. Study of 2 cases]. AB - Two cases of Burkitt cell leukaemia (ALL3) occurring 60 and 51 months respectively after treatment of Hodgkin's disease (HD) are described. Clinical, cytological, immunological and cytogenetic features in these patients were comparable with those of the 6 previously published cases and with de novo ALL3. The prognosis of these secondary ALL3 is uniformly poor: our 2 patients died 2 and 14 days after the start of combination chemotherapy, and all the other cases survived less than 60 days after diagnosis. The significance of ALL3 occurring after HD is discussed: the association is probably not fortuitous, and its pathogenic mechanisms probably differ from those intervening in secondary myeloid leukaemias. PMID- 3330611 TI - [Cusp and fissure angle of inclination and occlusal surfaces in complete denture]. PMID- 3330610 TI - [The use of M13 phages in the cloning and sequencing of DNA]. PMID- 3330612 TI - [Ceramic blends for onlay bridges of non-fired alloys]. PMID- 3330614 TI - [Bilateral symmetry in complete denture]. PMID- 3330613 TI - [Orofacial design--new aspects using multicolor wax]. PMID- 3330615 TI - [Preparation of a metal long-lasting temporary arrangement using flexible silicon dies]. PMID- 3330616 TI - [Technical preparation of full porcelain bridges using Hi-Ceram System]. PMID- 3330617 TI - [From dental medicine to orthodontics]. PMID- 3330618 TI - [Dental laboratory work order for model preparation and its clinical significance (II)]. PMID- 3330619 TI - Notice to the readership. PMID- 3330620 TI - [Pulpodentinal aging: review of the literature and diagnostic conclusions]. PMID- 3330621 TI - [Cephalometric comparison of an ancient Anatolian tribe and modern population]. PMID- 3330622 TI - [Computerized tomography in the study of degenerative ataxia]. AB - We describe the computerized tomography findings in 85 patients affected with degenerative ataxias. Cerebellar atrophy was moderate in patients with Friedreich's disease (no. 28) and early onset cerebellar ataxia with retained reflexes (no. 10) and, in Friedreich's disease, it was mostly a late feature. On the contrary, in symptomatic patients with adult onset dominant cerebellar ataxia (no. 24), cerebellar atrophy was always present and often marked. However, it was absent in 3 asymptomatic affected relatives. Infratentorial and supratentorial atrophy were frequent findings in idiopathic late onset cerebellar ataxia (no. 16). PMID- 3330623 TI - [Cerebellar ataxia and hypogonadism. Description of 4 cases]. AB - We describe the association of cerebellar ataxia and hypogonadism in four female patients. Clinical, neurophysiological, neuroradiological and endocrinological features are reported. Post-mortem findings in one case are also described. We show in our patients that, beside the cerebellum, both the supratentorial white matter and the peripheral nerve are involved. We suggest that this association can be considered as a "multiple system atrophy". Furthermore, since hypogonadism is hypergonadotropic in three patients and hypogonadotropic in one, the endocrine pattern appears to be heterogeneous. PMID- 3330624 TI - [Concordance of carotid bruit and positivity of computerized digital angiography of the epiaortic vessels in carotid stenotico-occlusive pathology]. AB - 256 patients (187 men and 69 women, aged 60 on the average) with carotid artery bruits, underwent digital subtraction angiography of the epiaortic vessels. The carotid artery stenoses of more than 50% and the carotid artery occlusions have been considered angiographically and compared with the evidences of the auscultation over the carotid bifurcation. The sensibility, specificity and overall accuracy of the carotid bruits were estimated. The sensibility was of 95%, the specificity of 83% and the overall accuracy of 92% when a carotid artery stenosis of more than 50% was detected. When a carotid occlusion was found the sensibility was of 71%, the specificity of 84% and the overall accuracy of 80%. When both the carotid stenosis of more than 50% and the carotid occlusion have been considered together, the sensibility was of 92%, the specificity of 84% and the overall accuracy of 90%. The Authors suggest that the carotid bruits are trustworthy witnesses of occlusive carotid artery disease. PMID- 3330625 TI - [Reliability of Doppler ultrasonography in relation to computerized digital angiography in patients with carotid bruit]. AB - The results of the carotid artery Doppler ultrasound examination were compared with those of digital subtraction angiography in 256 patients (187 men and 69 women) with carotid bruit. The hemodynamically significant stenoses of more than 50% and the occlusions in the 512 carotid arteries examined were considered and the sensibility, the specificity and the overall accuracy of the Doppler ultrasound examination were calculated. When a carotid stenosis was diagnosed a sensibility of 97%, a specificity of 95% and an overall accuracy of 96% was found, while, for the diagnosis of carotid occlusion, the extimated sensibility, specificity and overall accuracy was 95%. Therefore, the ability to recognize a normal or an occluded carotid artery was of 95% (we found 125 out of 131 normal carotid arteries and 52 out of 55 occluded carotid arteries), whereas a stenotic carotid artery was identified in the 97% of cases (316 out of 326 stenotic carotid arteries). When both diagnoses of carotid stenosis and carotid occlusion were considered together, the extimated sensibility, specificity and overall accuracy were of 98%, 95% and 98% respectively. So the probability of misdiagnosing was of 2% (we made 10 wrong diagnoses out of 512 carotid arteries examined). PMID- 3330627 TI - Experimental studies on the effect of hepatoprotective compounds. AB - The hepatopharmacological actions of Prostacyclin, 1-phosphate-4-amino 5 carboxamido-imidazole (AICA-P), Catergen, Silymarin and a thiazolidine compound were investigated by applications in in vitro and in vivo model systems. The usefulness of the in vitro system to screen for potential hepatoprotective agents and to investigate the molecular mechanism of these substances is shown. It was concluded that different patterns of hepatoprotective action were elaborated by the same drug depending on the model system used for testing. PGI2 and the thiazolidine compound showed remarkable protection in acute liver damage. However PGI2 circumvented only the CCl4 induced cellular injury, and was inactive in the galactosamine model system. The induction of cirrhosis could be modified by the simultaneous treatment with PGI2 or by the thiazolidine compound but the fully developed cirrhosis was not affected. On the contrary AICA-P and Silymarin treatment resulted in reduction of the amount of collagen in cirrhotic liver. PMID- 3330626 TI - [Migraine crisis and neurological focal signs of slow or absent resolution (complicated migraine)]. AB - Sixteen cases of vascular headache of the migraine type are referred in whom marked neurological manifestations occurred in a unilateral distribution as part of a migraine attack ("complicated migraine"). The neurologic disorders observed, in order of frequency, include 10 cases of motor hemiparesis, 3 cases of unilateral cerebellar syndrome, 1 case of sensory-motor hemiparesis and 1 case showing signs of the involvement of the motor nuclei of the bulb. The recovery of the motor, sensory, cerebellar and brainstem defects was very slow (average duration: 44.25 days; mode: 14 days) in twelve cases. Two patients showed residual neurological signs respectively after 1 and 7 years from the migraine attack. The patients histories indicate classic or common migraine with a relatively high frequency (80% of the patients experienced one or more crises per month). The most of cases (75%) were female patients. The patients, at time of the attack of complicated migraine, had a mean age years of 32. In ten cases first-grade relatives suffered from classic or common migraine; in no case was there any report of associated or complicated migraine among the relatives. In 4 of the 16 cases the CT scan showed an area of hypodensity consistent to the region of the brain expected to be suffering in view of the clinical type of neurological defect. The Authors take into consideration the controversial relation between complicated migraine with slow or incomplete resolution of neurologic signs and focal brain ischemia due to atherothrombotic infarct, pointing out that the present state of knowledge prevents the reaching of final conclusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3330628 TI - [Gastrectomy with the Roux-en-Y anastomosis and the use of mechanical compression sutures]. PMID- 3330629 TI - [The etiology and pathogenesis of spontaneous pneumothorax]. PMID- 3330630 TI - [Pneumatosis cystoides intestinalis]. PMID- 3330631 TI - [Fibrogastroduodenoscopy in the evaluation of late results of suturing perforated gastroduodenal ulcers]. AB - Results of a dynamic endoscopic examination of 213 patients after operations of suturing perforating gastric and duodenal ulcers are described. Stable healing of the ulcer was obtained in 20.2% of the patients. In 79.8% of the patients the ulcer failed to heal or recidivated. A comparison of roentgen findings and results of endoscopic examinations has shown that roentgen analysis gave the correct diagnosis but in 44.7% of the patients examined. PMID- 3330632 TI - [Development of the surgical treatment of gastrointestinal hemorrhage in the USSR]. PMID- 3330633 TI - [Metronidazole in the complex treatment of peritonitis of appendicular etiology in children]. AB - Metronidazole was used for treatment of 212 patients with peritonitis of appendicular origin. It resulted in lowered leukocytosis, elimination of the stab neutrophil shift, earlier reduction of the leukocyte intoxication index. The amount of suppurations of postoperative wounds decreased from 17% to 4.3%. The amount of reoperations was 2.4% instead of 5.4%. Metronidazole is recommended for treatment of acute appendicitis complicated by peritonitis. PMID- 3330634 TI - [Catecholamine neuron systems as revealed by immunohistochemistry]. PMID- 3330635 TI - [Clinical-technical methods of complete prosthetics]. PMID- 3330637 TI - [History of crowns and veneer crowns]. PMID- 3330636 TI - [Clinical-technical methods of complete prosthetics]. PMID- 3330638 TI - [Clinical use and technology of adhesive bridges]. PMID- 3330639 TI - [Repairs of prostheses and their causes of fracture]. PMID- 3330640 TI - [Development and constructive design of removable partial dentures for a patient with cleft]. PMID- 3330642 TI - The immune response and alterations induced by immunosuppressive drugs. PMID- 3330643 TI - Mycotic infections complicating heroin addicts, AIDS and other immunocompromised host conditions. PMID- 3330641 TI - Historical processes and biological structure of the populations. Example from the Island of Korcula. AB - The importance of geographical distance as a determining factor of the population's biological and socio-cultural structure was studied on the island of Korcula, Yugoslavia. Migrational kinship coefficients, biological and linguistic distances were analysed in respect to isolation by distance, using Malecot's model. The fit of the model is highly significant for migrational kinship, linguistic, anthropometrical and physiological distances, while for morphometrical distances of metacarpal bones and dermatoglyphic distances, it is not adequate. The major conclusions reached through this analysis are in concordance with the known historical events in the entire region. PMID- 3330644 TI - [Experimental cystitis in the rat and the therapeutic effect of a single dose of fosfomycin trometamol]. PMID- 3330645 TI - [Chemoprevention using fosfomycin trometamol in transurethral resection of the prostate: multicenter controlled clinical study]. PMID- 3330646 TI - [Single-dose therapy of urinary tract infections in the adult]. PMID- 3330647 TI - Resistance to clinically important antimycotic drugs in Candida spp. PMID- 3330648 TI - A manno-protein antigen of Candida albicans cell wall induces generation of anti tumor cytotoxicity in human peripheral blood lymphocytes. A comparative study between healthy donors and glioma bearing patients. PMID- 3330649 TI - [Importance of anaerobic micro-organisms in intra-abdominal infections]. PMID- 3330650 TI - Antimicrobial agents and opsonic defence. PMID- 3330651 TI - [Critical evaluation of the relation of antibiotics to the functions of professional phagocytes]. PMID- 3330652 TI - Transferrins and defence against infection. PMID- 3330653 TI - [Immunological profile of high-risk patients treated with different types of immunosuppressive therapy]. PMID- 3330655 TI - William Tyson Kendall. Reflections on a pioneer. PMID- 3330654 TI - Toxicology and hazard assessment of 1,3-dichloropropene (Telone II). AB - Potential adverse health effects from occupational exposure to 1,3-dichloro propene (DCP) are reviewed and hazards assessed. Further toxicologic evaluations should be conducted using only high-purity material that is free from possibly confounding impurities and stabilizers. Safety considerations when handling the material are included. PMID- 3330656 TI - Glucose metabolism in a pony mare with a tumour of the pituitary gland pars intermedia. AB - A case of pituitary dependent hyperadrenocorticism in a horse is reported. Clinical signs included hirsutism, polydipsia and general debility. The horse was persistently hyperglycaemic and glucose values were unchanged following subcutaneous administration of insulin. Resting cortisol values were normal, but dexamethasone suppression of cortisol concentration was shorter than normal. Plasma glucose, cortisol, insulin and glucagon concentrations were measured as part of an intravenous glucose tolerance test. The patient responses were different from those in a control pony. PMID- 3330657 TI - Towards stress-resistant persons: a stress management approach to the treatment of anxiety. AB - With the reported increase in life stress in recent years, it is important to understand the relationship between such stress and health. It would be of further value if efficacious and time-limited approaches for coping with life stress were to be developed. This paper presents a brief history of the literature on stress, health, and illness. It focuses particular attention on persons who cope adequately with life stress--stress-resistant persons. It also outlines a four-step program to teach these effective copying skills to more vulnerable persons, and presents preliminary findings and the theoretical and clinical issues involved in its implementation. PMID- 3330658 TI - The validity of an interview to assess a patient's drug taking. AB - The most practical method of assessing patient compliance is to ask the patient for a self-report; but, how valid is such a report? This study compared one particular interview question to a pill-count measure by studying 98 patients who visited their family physician, received medication instructions, and were interviewed in their homes ten days later. The interview question identified 80 percent of the true noncompliers, as assessed by the pill count (sensitivity). However, the interview question was not equally sensitive for all subgroups of patients. Results for younger patients, patients receiving renewals rather than new prescriptions, and patients taking more than one drug were not as accurate, showing sensitivities of 75 percent, 40 percent, and 60 percent, respectively. PMID- 3330660 TI - Estimating the combined effect of several disease precursors in health risk appraisal. AB - Health risk appraisal is an attractive health education technique but suffers from methodologic weaknesses. Many of the problems center on the formula that is usually used to estimate the combined effects of different disease precursors. The formula does not reflect current models of disease causation, underestimates the effects of protective factors, and confounds the effects of different precursors. We suggest a modification that resolves these problems by estimating the prevalence and associated composite relative risk for each combination of precursors before calculating the numerical estimate of combined risk. This method can be applied to the many diseases for which the data needed to support a multivariate approach are not available. We recommend its incorporation into existing appraisal instruments. PMID- 3330659 TI - Congenital malformations as a cause of neonatal and postnatal death in Massachusetts (1970-1980). AB - Massachusetts birth and death certificate tapes for the years 1970-1980 were linked and analyzed to determine causes of death in the neonatal and postneonatal periods and to identify any related sociodemographic factors. Our analysis suggests that, although the neonatal mortality rate declined by about 43 percent, the postneonatal mortality rate remained relatively unchanged. Perinatal problems remained the principal cause of death during the neonatal period, throughout the decade. In the postneonatal period, congenital malformations became a leading cause of death toward the end of the decade because of a reduction in mortality from infectious diseases and perinatal problems. Infants born to mothers under 18 and over 34 years of age had the highest death rates from congenital birth defects. Higher mortality rates caused by congenital malformations were found in the more industrialized areas of Massachusetts. Further declines in infant mortality rates in Massachusetts will depend on preventive measures to reduce the incidence of congenital malformations. PMID- 3330661 TI - Effectiveness of physician antismoking advice. AB - The Dartmouth Primary Care Cooperative Information (COOP) Project conducted a controlled trial on the impact of antismoking advice from office-based physicians. Eighteen primary care medical practices were randomly assigned to be intervention or customary care practices. Medical personnel assigned to the intervention practices were to systematically identify cigarette smokers (among patients aged 35 to 59 years making an office visit), advise them to quit smoking, and provide educational materials. A random sample of 258 smokers was identified and followed-up four months later. Intervention-group smokers were more likely to report being advised to quit smoking (77 percent versus 47 percent) and to attempt quitting (39 percent versus 31 percent), but had success rates similar to those of the other group (6 percent versus 7 percent). We conclude that the medical office is an excellent place to identify large numbers of smokers and initiate attempts at quitting, but find that simple antismoking information and advice are not enough to improve cessation rates. PMID- 3330662 TI - Pilot survey of the prevalence of neurologic disorders in the Parsi community of Bombay. AB - There is a paucity of trained neurologists in developing countries. We designed a questionnaire to rapidly screen a community of 851 people (Parsis living in a colony in Bombay, India) for possible neurologic diseases. This questionnaire was pretested and found to have a sensitivity of 100 percent for detecting epilepsy, febrile seizures (only in children), completed stroke, peripheral neuropathy, movement disorders, cerebral palsy, mental retardation, and severe dementia. The screening questionnaire was administered by trained lay health workers. One hundred and sixty-three people were identified by this questionnaire as possibly having neurologic disease. Neurologists later examined these 163 people and found that 80 of them actually suffered from at least one of the neurologic diseases of interest (positive predictive value = 48 percent). The most common neurologic disorders were peripheral neuropathy (32 cases), essential tremor (13 cases), stroke (12 cases), Parkinson's disease (six cases), and epilepsy (four cases). PMID- 3330663 TI - Primary care and health promotion: a model for preventive medicine. AB - This paper examines the potential role of the primary care physician in health promotion, specifically the use of behavioral change technologies to modify risk behavior. The primary care physician's strategic position to help people modify risk behavior is discussed, and the available data on the health promotion attitudes and services of these physicians are reviewed. The principles and procedures of behavior modification underlie not only the model proposed for risk assessment and reduction, but are applied to the task of changing and maintaining physician behavior as well. Cost-effectiveness research and the role of reimbursement for primary care prevention services are discussed. Recommendations are made for future health policies, practices, training, and research that might encourage preventive behavioral services in primary care. PMID- 3330665 TI - Wisdom and Western science: the work of Dr Wu Lien-Teh. PMID- 3330664 TI - Public health: myth, mysticism and reality. PMID- 3330666 TI - Determination of metabolites (including thioethers) of mutagens and/or carcinogens as exposure indicators. PMID- 3330667 TI - "By whose efforts the tropics have been made safe:" the work of Sir Patrick Manson. PMID- 3330669 TI - Of men and mosquitos: the story of malaria. PMID- 3330668 TI - The seroepidemiology of hepatitis A and B in the Asia-Pacific region. PMID- 3330670 TI - Prince Mahidol--father of public health and modern medicine in Thailand. PMID- 3330671 TI - [Contribution of radiological technics to the study of the mandibular canal. Application to human fossils and comparison with modern man and Pongidae]. AB - Fossil mandibles from the "La Chapelle-aux-Saints" Man and Cro-Magnon "old man" are considered to be representative of Neanderthal and Cro-Magnon era. Radiographic studies of such mandibles - including C. T. Scan and panoramic views in common use in maxillofacial surgery - allowed the authors to make useful comments: the mandibular canals are nearly similar to those in Modern Man and quite different from those in Pongidae; the imaging was of adequate quality for a good evaluation of fossil internal structures. PMID- 3330672 TI - Stress-associated depression in cellular immunity: implications for acquired immune deficiency syndrome (AIDS). PMID- 3330673 TI - Splenic lymphocyte production of an endorphin during endotoxic shock. AB - Endogenous opioids have been reported to elicit some of the pathophysiologic responses to endotoxic shock by binding to the delta-opiate receptor. We have previously reported the production of immunoreactive (ir)-endorphin by B lymphocytes treated with bacterial lipopolysaccharide (LPS). We postulated that this lymphocyte-derived ir-endorphin may be an extrapituitary source of the endogenous opioid component associated with the pathophysiology of endotoxic shock. To test this hypothesis, we chose to study the LPS-sensitive (C3HeB/FeJ) and -resistant (C3H/HeJ) inbred mouse model. We treated these mice with intraperitoneal injections of LPS or B-lymphocyte-derived ir-endorphin. The LPS sensitive mice presented with a severe hypothermic and pathophysiologic response pattern when treated with LPS or with ir-endorphin. The LPS-resistant mice, which were unresponsive to the LPS, however, presented with the typical hypothermic and pathophysiologic responses to the ir-endorphin. Immunofluorescence on the splenic leukocytes in the LPS-treated mice showed significant ir-endorphin present only in the LPS-sensitive mice at a time point preceding onset of the pathophysiologic response pattern. Taken together, this evidence strongly suggests a role for B lymphocyte-derived ir-endorphin in the pathophysiology of endotoxic shock. The implications of immune system regulation of neuroendocrine function are discussed. PMID- 3330674 TI - Significance of increased secretion of glucocorticoids in mice and rats injected with bacterial endotoxin. AB - Injection of mice or rats with lipopolysaccharide (LPS) is associated with an increased secretion of glucocorticoids. The high level of mortality following injection of LPS that is noted in adrenalectomized rats can be reversed by dexamethasone or corticosterone. That histamine may be an endogenous mediator of the release of corticosterone caused by LPS is suggested by an attenuation of this corticosterone response by promethazine, an H1 antihistamine. Additional support that LPS-dependent glucocorticoid secretion is mediated, in part, by histamine, is suggested by spleen cell transfer studies revealing differences in the induction of histidine decarboxylase (HDC) synthesis and corticosterone release by the C3H/HeN and C3H/HeJ strains of mice that are differentially sensitive to LPS effects. These and other data on increased levels of histamine and HDC during mitogen-induced lymphocyte blastogenesis, as well as experiments revealing immunomodulatory effects of histamine and histamine agonists and antagonists on lymphocyte blastogenesis, are consistent with the hypothesis that following infection with gram-negative bacteria, the histamine-induced increase in glucocorticoid secretion results in inhibition of HDC in splenocytes, a concomitant attenuation of histamine production, and a resulting return to immune homeostasis. PMID- 3330675 TI - Jose Leal Prado (1918-1987) PMID- 3330677 TI - Characterization of inducible lysozyme activity in the hemolymph of Rhodnius prolixus. AB - 1. The characterization and partial purification of an induced lysozyme activity in the hemolymph of adult Rhodnius prolixus inoculated with Micrococcus lysodeikticus is described. 2. Little or no activity against M. lysodeikticus appeared in the first hours after inoculation, but the activity increased reaching a maximum 4 days later, which was maintained to day 12. 3. The activity was characterized as lysozyme on the basis of the following considerations: 1) pH optimum and thermostability at acidic pH; 2) rate of lysis negatively dependent on ionic strength; 3) binding to SP-Sephadex at pH 5.5; 4) apparent molecular weight of 15 kDal. 4. Crude or semi-purified enzyme preparations showed a high degree of stability during handling, freezing and thawing, and standing at 5 degrees C. 5. Incubation of abdominal fat bodies from treated insects resulted in the release of activity into the medium. 6. The relationship between induced lysozyme activity and its role as an insect defense mechanism is discussed. PMID- 3330676 TI - Pharmacological and toxicological profile of benzyleugenol, a phenylpropene derivative possessing anticonvulsant properties. AB - 1. Benzyleugenol (BE), a phenylpropene derivative, protects rats and mice against maximal electroshock seizures and has a protective index superior to that of phenobarbital. The present paper describes experiments carried out to further characterize the pharmacological and toxicological profile of this compound. 2. BE, at a dose range of 100-400 mg/kg ip, was inactive when tested for the following effects: analgesia, as measured by the hot plate and acetic acid writhing methods; neuroleptic-like effects, when tested by the catalepsy and palpebral ptosis, conditioned avoidance response and apomorphine-induced stereotypies methods; and anxiolytic effects, measured by the shock-elicited aggressiveness of mice. In contrast, tolerance to the anticonvulsant effect of BE, at dose range of 240-800 mg/kg orally, developed in mice and rats after 10 to 40 days of continued treatment. 3. BE, at dose range of 104-800 mg/kg orally, proved to be remarkably safe when chronically administered to laboratory animals. Thus, 3 to 6 month administration of large BE doses to rats and mice did not affect body weight, behavioral measures, serum and blood tests, or hematological parameters. Anatomopathological examinations of viscera of BE-treated animals did not reveal alterations which could be attributed to drug treatment. 4. Daily treatment up to 3 months of male rats and mice with BE, at a dose range of 80-800 mg/kg orally, did not affect the reproductive capacity of the animals. Pregnant females treated with BE during different periods of gestation gave birth to litters similar to those of control females; when adult, BE and control litters performed equally well in a passive avoidance task. 5. These results were compared with those of known anti-epileptic drugs, such as phenytoin, phenobarbital and valproic acid, and it is suggested that BE deserves further research as a potential candidate for the treatment of epilepsy. PMID- 3330678 TI - A test for the evaluation of ingestion by neutrophils. AB - A rapid, simple and inexpensive technique was developed to evaluate particle ingestion by neutrophils (PMNs) and alternatively investigate the activity of the complement system. Whole blood specimens, obtained in EDTA, were mixed with a suspension of activated Baker's yeast in minimal volumes (3 and 1 drops of each, respectively). The mixture was incubated at 37 degrees C for 1 h and centrifuged at 200 g for 5 min. The sediment was resuspended in FBS and blood films were stained with Giemsa. Two hundred PMNs/film were counted and the percentage of phagocytizing cells and the mean number of ingested particles per cell were determined. Samples from 11 male and 15 female subjects showed mean rates of 80.0 +/- 10.8 (SD) and 83.3 +/- 5.8 of PMNs with phagocytic vacuoles containing 2.9 +/ 0.5 and 3.2 +/- 0.7 ingested particles/cell, respectively. There were no statistically significant differences between sexes. PMID- 3330679 TI - Antipyretic activity of an aqueous extract of Zizyphus joazeiro Mart. (Rhamnaceae). AB - Bark infusions of Zizyphus joazeiro Mart. (Rhamnaceae) have been employed in Northeastern Brazil as a remedy for fever. This study investigated the antipyretic activity of an aqueous extract of the plant in rabbits rendered febrile by intravenous injection of E. coli endotoxin. Fever responses were significantly decreased (P less than 0.05) by the oral administration of a bark infusion of Z. joazeiro Mart. These results lend support to the popular use of infusions of this plant in folk medicine as a remedy for fever and suggest that the characterization of the principle(s) responsible for such activity deserves further investigation. PMID- 3330680 TI - The contribution of animal experiments to knowledge of the relationship between diet and cancer risk in humans. PMID- 3330681 TI - Fat and breast cancer. AB - Breast cancer mortality and incidence in different countries show a strongly positive correlation with the per caput consumption of fat. In addition, the disease has increased among the Japanese, both in Japan and in the United States, and in both groups fat consumption has been increasing. In contrast, both case control and prospective studies have on the whole failed to confirm the relationship. Despite these negative findings, the hypothesis that fat causes breast cancer has continued to be popular. The evidence for fat as a cause of breast cancer seems to have been exaggerated, and insufficient attention given to alternative explanations for the geographical correlations and for the changes among the Japanese in the frequency of the disease. These include the effects on breast cancer risk of body weight, body size, age at menarche (all influenced by excess calories) and age at the birth of the first child, as well as effects of obesity on the fatality rate in breast cancer. Evidence is lacking that the source of calories is important. PMID- 3330682 TI - The epidemiology of selenium and cancer. PMID- 3330683 TI - Retinol, beta-carotene and cancer. AB - Evidence from epidemiological dietary studies does not demonstrate an association between retinol intake and the risk of cancer in developed countries. There is, however, an inverse association between beta-carotene intake and the risk of cancer. Evidence from prospective biochemical epidemiological studies demonstrates that low serum retinol is associated with a high risk of cancer but only within about the first three years, indicating that it is probably a metabolic consequence of cancer. A low serum beta-carotene level is also associated with a high risk of cancer, but here the association persists for many years before the diagnosis of cancer, indicating that it probably also precedes its development. The dietary and serum studies are therefore consistent in showing a long-term inverse association between beta-carotene and the risk of cancer. This may be due to beta-carotene affecting the risk directly, or may reflect an indirect association with some other component of vegetables or with a non-vegetable component of diet that is itself related indirectly to vegetable consumption. Whatever the explanation, the association represents an interesting epidemiological clue to the relationship between diet and cancer. PMID- 3330684 TI - Diet and faecal genotoxicity. AB - There are many known DNA-damaging substances in the diet, but their relevance to the aetiology of colorectal cancer is not clear. The examination of faecal contents provides the best available non-invasive way of studying 'exposures' of the colorectal mucosa including those that are of dietary origin. In particular, faecal genotoxicity is studied as a potential intermediate In particular, faecal genotoxicity is studied as a potential intermediate between dietary genotoxins and colorectal cancer. About 100 investigations of the DNA-modifying effects of faeces have been published in the 10 years since Bruce et al first observed faecal mutagenicity in extracts of stool from four human volunteers. In this review, the studies relating to diet and faecal genotoxicity in humans are summarized. In addition, preliminary data are given from an investigation of diet and a potent class of faecal genotoxins, the fecapentaenes. PMID- 3330685 TI - The reliability and validity of dietary data as used in epidemiology. PMID- 3330686 TI - Dietary exposure to N-nitroso compounds and the risk of human cancer. PMID- 3330687 TI - Craniomandibular disorders in elderly with psoriasis. AB - A questionnaire survey was carried out to determine the prevalence of craniomandibular (CM) disorders in relation to age in psoriasis. Of the 1776 psoriatics, 85.4% responded; 1050 of them had psoriasis with skin symptoms only (P), and 400 had both skin and joint symptoms (PA). No statistically significant differences could be found between older (greater than or equal to 65 yrs) and younger (less than 65 yrs) psoriatics in either the P-group or the PA-group as regards the severity of subjective symptoms of CM disorders. In the P-group the younger psoriatics reported more frequent (30%) subjective symptoms than the older ones did (19%) (p less than 0.05), but no difference was found in the PA group (51% and 41%, respectively) (NS). The most frequently reported symptoms in all age groups were temporomandibular joint (TMJ) sounds and TMJ pain during function. TMJ sounds were significantly less frequently reported by the older than the younger psoriatics both in the P-group and the PA-group (p less than 0.01 and p less than 0.05, respectively). It can be concluded that, apart from TMJ sounds, the frequency and severity of symptoms of CM disorders are not related to age in psoriasis. PMID- 3330688 TI - Animal models of brain ageing and dementia. AB - Six animal models of human brain ageing or of age-related diseases, especially Alzheimer's disease, are evaluated. Special emphasis is laid on comparing the neuropathological symptoms found in aged human brains or in Alzheimer patients, with the neuronal symptoms induced experimentally by the different treatments described here. For each model, the experimental methods for induction of the neuropathological symptoms (lipofuscin accumulation, senile plaques, neurofibrillary degeneration, etc.) and for their identification are discussed. In addition, the behavioral significance of each animal model is evaluated in the content of its meaning for cognitive alterations in senescence or in dementia. PMID- 3330691 TI - Use of microcomputers in health and social service applications in developing nations. AB - The microcomputer is creating something of a revolution in many developing nations where historically there has been a lack of access to computer power at all levels of the health sector. For the first time, practitioners and researchers, often trained in computer techniques for developing countries, have access through microcomputers to data and information manipulation in their local workplace. While the history of microcomputers in such settings is short, this article presents early evidence from several countries which indicates the usefulness of various applications. The majority of the applications reported in the literature from clinical and research laboratories is made up of national data base systems and special studies of morbidity and mortality. Secondary applications, including assistance in biographical searches and word and graphics processing, are also reviewed in this article. A summary of the most utilized microcomputer hardware configurations completes the review. PMID- 3330689 TI - Age-correlated changes in the lupus erythematosus antigens Ro, La, Sm and RNP of the thymus gland. AB - The concentrations of the Sm, RNP, La and Ro antigens of thymus glands from rats were determined depending on the developmental stage of the animals. It was found that lupus antigens strongly decrease after birth. Parallel with this change, the activities of the enzymes DNA polymerase alpha and terminal nucleotidyl transferase in the thymus glands drop during maturation and ageing. These biochemical analyses were supported by immunofluorescence studies using human thymus glands. Moreover, it is documented that a redistribution of Sm and Ro occurs during development. Focusing on Sm, fetal thymus glands contain this antigen predominantly in the cytoplasm, while in immature, mature or old animals Sm is found almost exclusively in the nucleus. From these data we conclude that the amounts of the lupus antigens are additional parameters for the age correlated function of thymocytes. PMID- 3330690 TI - Computer modeling of clinical judgment. AB - Four main developments leading to computer modeling of clinical judgment are described in this paper. These include information processing psychology, clinical vs. statistical prediction studies, behavioral decision theory, and Bayesian decision analysis approaches. One clear catalyst in these developments has been the computer, which has been used as an information management tool rather than a data-processing device. Future directions of these efforts are delineated, and problems as well as prospects of computerizing clinical judgment are described. PMID- 3330692 TI - Computers in the cognitive rehabilitation of brain-injured persons. AB - Currently there is a rapid expansion of work among rehabilitation professionals in applying computer-assisted instructional technology to remediate cognitive deficits resulting from brain injury. The present article presents a framework for relating the various theoretical, empirical, and clinical challenges raised by the coalescence of two such recently emerging disciplines as computer-assisted instruction and cognitive rehabilitation. These challenges are presented from the perspectives of diverse disciplines, including cognitive science, rehabilitation professions, and computer science. A set of guiding principles are derived for evaluating the potential efficacy of currently existing programs and for directing future developmental work in software design, evaluation research, and service delivery. PMID- 3330693 TI - The radiology information system: its evolution and current status. AB - Radiology information systems (RIS) have developed over the past 20 years as a specialized area of medical informatics. Although an increasing number of radiology departments utilize such systems, the majority do not. Perhaps this is because no commercially available system has yet demonstrated its ability to provide cost-effective solutions to the diverse problems of different departments. This review begins with a brief history of RIS to point out some approaches that have proven successful and some that have not. Learning about the historical development of RIS also helps understand many of the features that are found in current systems. The bulk of the article is devoted to a detailed discussion of the functional modules found in RIS, including patient registration and data base management, examination scheduling, process control, film file management, diagnostic reporting, financial packages, and management statistics. These discussions emphasize the wide range of activities and problems found in different radiology departments and the wide range of techniques utilized by RIS. General issues of designing or selecting, installing, operating, and optimizing a RIS are discussed briefly. A final section points out areas for future development and expansion of RIS, giving special attention to the incorporation of digital image information into overall radiology systems. PMID- 3330694 TI - The epidemiology of rheumatoid disease: past and present. AB - The epidemiology of rheumatoid arthritis is poorly defined. We know neither how long rheumatoid arthritis has been a major disease, nor whether its incidence is decreasing. If it is decreasing, is this because of the contraceptive pill or some other variable? We do know that the disease occurs worldwide and that there may be increased prevalence among urban living individuals, compared to their rural counterparts. To some extent the disease 'runs in families', but heritibility is low. Concordance among monozygotic twins is only 32 per cent. Women develop the disease more frequently than men. The prognosis for black males is said to be better than for white females. Whether seronegative 'rheumatoid arthritis' should be considered part of the same disease process is unknown. An agreed definition for rheumatoid arthritis is essential before meaningful genetic and immunogenetic data can be developed. However, it is unclear whether the term rheumatoid arthritis should only be given to those individuals with seropositive erosive disease or whether we should include a self-limiting process of poorly characterized change that is sometimes seen, for example, in the first degree relatives of index cases with disease. The ARA criteria for rheumatoid arthritis are unhelpful since 'possible' and 'probable' rheumatoid arthritis patients almost certainly do not have rheumatoid disease. Moreover, the majority of patients with 'definite' rheumatoid arthritis are seronegative. These subjects may be differentiated from seropositive patients on epidemiological, familial, clinical, immunogenetic, and perhaps radiological grounds. The consensus view is that the DR4 allotype occurs more frequently in severe seropositive disease than in severe seronegative 'rheumatoid arthritis'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3330696 TI - Are major histocompatibility system class III products independent markers for susceptibility to rheumatoid arthritis? AB - Three components of the complement pathway C2, Factor B, and C4 are coded for by four genes C2, Bf, C4A, and C4B in the class III region of the major histocompatibility system in man. Studies of the polymorphism of these plasma proteins have shown associations of BfS, C2C, and C4B3 (2.9) with RA. Family studies have shown that these markers occur together, usually on DR4 positive haplotypes and in particular on the A2-Cw3-Bw62-C4B3-C4A3-BfS-C2C-DR4 haplotype. It is argued that Class III gene products are unlikely to be independent markers of susceptibility to RA. PMID- 3330695 TI - Multiple HLA associations and disease susceptibility. AB - A strong association between a particular HLA antigen and a given disease may mask a secondary, weaker association. Applying a stepwise analysis to published HLA-DR frequencies in rheumatoid arthritis demonstrates an increased frequency of DRI not otherwise apparent. PMID- 3330697 TI - Rheumatoid arthritis: inheritance and association with other autoimmune diseases. AB - This paper reviews the significance of the associations between rheumatoid arthritis (RA) and both diabetes mellitus and autoimmune thyroid disorders (ATD). All three disorders are thought to result from an interaction between genetic susceptibility and environmental factors. There is a probable real but not dramatic aggregation of insulin-dependent diabetes mellitus (IDDM) in the families of RA probands and a significant aggregation of ATD in both first- and second-degree relatives of RA probands. HLA-linked genes predispose to all three disorders while genes linked to Gm have been implicated in predisposition to RA and ATD. Within the HLA region two or more genes may predispose independently to RA; one of these genes is in linkage disequilibrium with HLA-DR4 and a second is in linkage disequilibrium with DR1 and 3. The familial aggregation of RA and IDDM is at least partially attributable to a single gene linked to HLA-DR4 predisposing to both disorders. By contrast, although 'DR4 negative RA' seems more frequent in sibships containing members with ATD, the familial aggregation of RA and ATD cannot be accounted for by a single gene linked to HLA predisposing to both disorders. Neither can this familial aggregation be accounted for by a single gene linked to Gm predisposing to RA and ATD so that any genetic predisposition common to both disorders is likely to involve at least a third locus which is still to be defined. A simple model with an interaction between at least three independent genetic loci and genetic heterogeneity is proposed to account for the known facts concerning the genetic susceptibility to RA. PMID- 3330698 TI - Genetic analysis in rheumatoid arthritis. AB - The use of heritability studies, haplotype sharing, and lod score analysis are reviewed. Twin and family studies show that any genes conferring susceptibility to rheumatoid arthritis must have a relatively low penetrance. This is a serious obstacle to linkage analysis in families. Where there is a population association, as with DR4, studies of haplotype sharing by affected sibs may yield more information if the observations are compared with the sharing predicted from the population association. PMID- 3330699 TI - Analysis of the HLA association with rheumatoid arthritis. AB - Definitive determination of the HLA linked gene or genes for susceptibility to RA will be achieved (1) by the accumulation of an adequate body of data on the haplotype frequencies in a random set of RA patients and controls and (2) by further study of other loci in the DR region, involving the use of DNA probes as well as conventional techniques. Indirect evidence is here put forward to suggest that it may turn out that some part of DR4 specificity itself may be directly involved in increasing susceptibility and that DR1 epitopes may be involved in a similar way. PMID- 3330700 TI - HLA and rheumatoid arthritis: an analysis of multicase families. AB - In a study of multicase RA families, significantly raised frequencies of the HLA antigens DR4, DR1, Bw62, Cw3, A2, A31 and significantly lower frequencies of DR2, DR3, and B8 were found in probands compared to normal controls. When haplotype frequencies were compared between probands and controls, two haplotypes A2-B44 DR4 and A2-Bw62-DR4 were at higher frequency in probands. These differences no longer reached significance when only DR4-containing haplotypes were compared between probands and controls. A significantly lower haplotype frequency of A1-B8 DR3 was observed in probands compared to controls. This difference did not remain significant when only non-DR4 haplotypes were compared. Using an affected sibling pair ratio method, significant linkage between HLA and RA was found (P less than 0.01). Significant linkage was also observed between HLA and seropositivity. Analysis of Hardy-Weinberg equilibrium for the DR locus did not support the suggestion that DR4-associated RA susceptibility was inherited as a dominant trait. In addition it did not support the notion of an additive effect of DR4 and DR1 in RA susceptibility as these antigens were not found together more frequently than predicted by their individual gene frequencies. PMID- 3330701 TI - [Ultrasonographic verification of clinical symptoms of congenital dysplasia of the hip joint in infants]. PMID- 3330702 TI - [Vascularized spongio-cortical bone transplant in the treatment of pseudarthrosis of the navicular bone]. PMID- 3330703 TI - [Advances in AIDS research]. PMID- 3330704 TI - [An experimental study of auxiliary partial liver allotransplantation]. PMID- 3330705 TI - [Protective effect of PGI2 on experimental ARDS and factors influencing it]. PMID- 3330706 TI - [Effect of insulin levels in the portal venous system on the postshunt liver]. PMID- 3330707 TI - [Preliminary study on the antimutagenesis of vegetables and fruits]. AB - Possible antimutation of 108 preparations of 91 kinds of vegetables and fruits on Salmonella typhimurium TA98 and TA100 mutants was tested. 4-nitroquinoline-N oxide (4 NQO), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), aflatoxin B1 (AFB1) and benzo (a) pyrene (BaP) were used as mutagens. The results showed that 67 (62%) preparations had antimutagenic action in vitro to different degrees. 9.6% of all preparations showed inhibition action on 4 NQO in TA100 mutant and 12.3%, in TA98, 5% on MNNG in TA100, 38% on AFB1 in TA100 and 45.1% in TA98, 28.9% on BaP in TA100. This experiment provides a scientific basis to the study of food resources as prevention of carcinogenesis. PMID- 3330708 TI - [Primary anorectal malignant melanoma--report of 7 cases and review of literature]. AB - From 1956 to 1985, 7 patients with primary anorectal malignant melanoma were studied by clinicopathology and observed by light and electron microscopes. The sex ratio of male and female was 2:5. The mean age was 59.4 years. The main presenting symptoms were bloody stool and a palpable mass in the anus. Because these symptoms are non-specific, early diagnosis is very difficult. The disease course ranged from 1.5 to 21.5 months with an average of 6.7 months. At present, the combination treatment is advocated, and radical operation is still the treatment of choice. This tumor has a very poor prognosis. Grossly, the tumor often showed nodular or polypoid shape. Histologically, there were various forms, such as epithelial, spindle and balloon-like cells etc.. Ultrastructurally, melanin corpuscles and vimentin (intermediate filaments) were found in all. In this paper, pathogenesis, morphology and prognosis are discussed. PMID- 3330709 TI - [Benign tumor and pseudotumor of the gallbladder--report of 40 patients]. AB - Benign tumor and pseudotumor of the gallbladder are infrequently reported in our country. In this paper, 5 patients with benign tumor (3 tubular adenoma, 1 leiomyoma and 1 fibroma) and 35 pseudotumor (26 cholesterol polyps and 9 inflammatory polyps) of the gallbladder are presented. Most patients presented a typical clinical manifestation of chronic cholecystitis. Oral cholecystography gave a lower detection rate. B-ultrasonography was able to show the presence of neoplasm in the gallbladder (37/40). Correct diagnosis was established by operation and pathology. In this series, all patients were cured by cholecystectomy. The authors believe that, for the neoplasms detected by B ultrasonography with definite clinical symptoms or with a diameter of more than 1.0 cm, cholecystectomy is indicated. For those older or weaker patients with milder symptoms or with neoplasms less than 1.0 cm in diameter, periodic B ultrasonography follow-up is suggested. PMID- 3330710 TI - In vitro chloroquine resistant Plasmodium falciparum in Calcutta and its sensitivity to qinghaosu (artemisitene). PMID- 3330711 TI - In vitro antimalarial activity of neem (Azadirachta indica A. Juss) leaf and seed extracts. PMID- 3330712 TI - Immunofluorescence test in the seroepidemiology of malaria around Delhi. PMID- 3330713 TI - Specific IgM and IgG antimalarial antibody responses in paired samples from malaria patients. PMID- 3330714 TI - Studies on the development of Plasmodium vivax in Anopheles subpictus. PMID- 3330715 TI - Studies on the detection of malaria at primary health centres. Part III. Parasitological profile of population surveyed for malaria through passive case detection. PMID- 3330716 TI - [Fanconi's anemia: in vitro tests for the individualization of heterozygotes]. AB - Fanconi's anaemia (FA) is an autosomal recessive mutation associated with constitutional chromosome aberrations. Patient's cells show increased susceptibility to different mutagens, especially bifunctional alkylating agents. Asymptomatic heterozygotes have a population prevalence of 1 in 300, and have been considered at risk for cancers. It has also been shown that their cells are especially sensitive to some chemicals in vitro. Laboratory tests are presented and discussed which are adequate for FA heterozygotes identification and for understandings the basic defect of this mutation. PMID- 3330717 TI - [Pathology caused by video terminals: critical review]. AB - A review of data resulting from the studies on health aspects of VDT operators is hereby presented and discussed by the Authors. In particular, researches on visual, musculoskeletal, dermatological and reproductive system alterations in VDT operators, together with psychological aspects, are evaluated and problems involved in radiation emission from VDTs are exposed too. Preventive measures are mentioned. According to the majority of the studies--up to now--no valid evidence of any abnormalities has been provided that can be specifically attributed to VDT work. The necessity of further researches on psycho-organic aspects of work with VDT is suggested by the Authors. PMID- 3330718 TI - [Traditional medicine and health in Mexico]. PMID- 3330719 TI - [The beginning of antisepsis in Mexico (1872)]. PMID- 3330720 TI - [Evaluation of the usefulness of a lyophilized culture medium used for growing Trichomonas vaginalis in the diagnosis of vaginal candidiasis]. PMID- 3330721 TI - [Preliminary evaluation of the treatment of menorrhagia with Danazol]. PMID- 3330722 TI - [Cholinergic agents in the treatment of Alzheimer's disease]. PMID- 3330723 TI - [Treatment of organic impotence]. PMID- 3330725 TI - Synthesis and hypoglycemic activity of peptides related to insulin fragment B22 25. PMID- 3330724 TI - Prediction of secondary and tertiary structures of 32 kD-like polypeptide and its possible role in oxygen evolution in photosynthesis. PMID- 3330726 TI - Inhibition of penicillinase by plant metabolites. PMID- 3330727 TI - Resection of the distal tibia in bone tumours. AB - The authors report five cases of tumour of the distal tibia treated by resection and reconstruction by autoplastic grafting and tibiotarsal arthrodesis with fixation by a Kuntscher nail or a plate. This type of surgery is indicated for the treatment of benign tumours, aggressive pseudotumours (Enneking stage 3), or for Enneking stage 1A or 2A malignant tumours. Infection was the most frequent complication (2 out of 5 cases, both of which healed after surgical cleansing). The long-term functional results were good in all cases, and there was neither pseudoarthrosis nor recurrence. PMID- 3330728 TI - The first homoplastic limb transplant according to the legend of Saint Cosmas and Saint Damian. PMID- 3330729 TI - [Eulogy for Prof. Robert Merger, 1903-1986]. PMID- 3330730 TI - [Endocrine, paracrine and autocrine mechanisms involved in follicular development]. AB - Development of a single follicle during the menstrual cycle is under control of hormones stimulating follicular maturation, ovulation and luteogenesis. Several factors intervene locally to avoid other follicles developing at the same time as the dominant follicle. These other follicles remain quiescent or go on to atresia. Atresia results from the action of several endocrine, paracrine and autocrine mechanisms which synergistically inhibit aromatase activity. The subsequent lack of oestrogens reduces granulosa cell multiplication. The oocyte will not become fertilizable before the preovulatory peak of LH, after the resumption of meiosis and after reaching the metaphase of the second meiotic division. Several factors are involved in this inhibition of spontaneous resumption of meiosis: cyclic nucleotides, sex steroids, somatostatin, oocyte maturation inhibitor(s) (OMI). Ovulation is related to breakdown of connective tissue synthesized by granulosa cells under the influence of FSH. Connective tissue lysis is dependent on proteolytic enzymes which are released and activated by FSH, LH and relaxin. A paracrine control could be involved in ovulation: LH induces the production of prostaglandin and relaxin by theca cells which, in turn, stimulate collagenase and proteoglycanase secretion by granulosa cells. PMID- 3330731 TI - [Definition and anatomo-pathologic classification of benign breast diseases]. AB - Most pathological changes in the mammary gland that are not tumours are fibrocystic diseases. Their classifications, at first purely descriptive, can now be used to predict the risks of cancer. All the same, there is no real parallel between these classifications and the difficulties in differential diagnosis that these lesions present for the pathologist. This is so true that the risk has to be defined by more objective markers than one morphological finding. PMID- 3330732 TI - [Oligohydramnios. Diagnosis. Etiology. Prognosis]. AB - We have studied 68 cases of severe oligohydramnios and compared them with the published literature on the aetiology, pathology, diagnosis, complications and prognosis. The principal aetiological features have been malformations of the fetal urinary tracts, intra-uterine growth retardation, high maternal blood pressure, nicotine poisoning and prolonged pregnancy. The perinatal mortality and morbidity, as well as the caesarean section rate, are raised because of the complications, such as the tetrad of oligohydramnios, prematurity, fetal distress in labour and post-maturity. When oligohydramnios is the sole presenting feature the prognosis for the fetus is better. PMID- 3330734 TI - [The use of methacholine challenge testing in the evaluation of chronic cough in adults]. PMID- 3330733 TI - [Hormone therapy and chemotherapy of endometrial cancer]. AB - It is correct to add hormone or chemotherapy in advanced metastatic disease of endometrial carcinoma and in recurrences. Large doses of hormone treatment have to be given. These are progestagens and the success rate with them, no matter which product is used, is approximately 30%. The use is limited by high blood pressure and the risks of vascular complications and metabolic upsets. Tamoxifen seems to the better tolerated and gives similar results. The response to hormone treatment depends on how sensitive the tumor is to the hormones. It is better when it has large numbers of progesterone receptors and it is of low grade. When the tumour is resistant to hormones, chemotherapy with cytotoxic drugs should be used. These drugs are adriamycine and mono or combined chemotherapy, but there is no protocol as yet that is better than any other. The debate about whether to use adjuvant treatment in stage I or II cases is open. It must be considered when the prognosis seems to be bad or there seem to be large risks of recurrences. PMID- 3330735 TI - [Normal upper limit of extrahepatic bile duct dimension by real-time ultrasonography--a reevaluation]. PMID- 3330736 TI - [Growth factors and leukemic blast progenitors]. PMID- 3330738 TI - [Late onset hemorrhagic cystitis after allogeneic bone marrow transplantation, and its preventive effect of bladder irrigation]. PMID- 3330737 TI - [Treatment of acute nonlymphoblastic leukemia in childhood: results of protocol ANLL-827 and ANLL-861 studies. Children's Cancer and Leukemia Study Group]. PMID- 3330739 TI - [Successful bone marrow transplantation in a case of severe aplastic anemia refractory to platelet transfusions]. PMID- 3330741 TI - [Annular elastolytic giant cell granuloma--a review of literature in Japan and three dimensional computer graphic analysis of elastolytic giant cells]. PMID- 3330740 TI - [Two cases of allogeneic bone marrow transplantation with psychoneurological symptoms possibly due to hypomagnesemia caused by cyclosporin A]. PMID- 3330742 TI - The encounter of Gaston Ramon (1886-1963) with formalin: a biographical study of a great scientist. PMID- 3330743 TI - [Methods of inducing experimental corneal mycosis]. PMID- 3330744 TI - [Methods and value of the measurement of temperature in ophthalmological practice]. PMID- 3330745 TI - The second K Prathap memorial lecture. Cancer of the lung: an immunocytochemical, histological and ultrastructural study. PMID- 3330747 TI - Evaluation of a microhaemagglutination test for the serological diagnosis of Mycoplasma pneumoniae infections. PMID- 3330746 TI - Pathology--its origins, progression and future. PMID- 3330748 TI - Preliminary results on the detection of mycolic acids from Mycobacterium leprae by gel permeation chromatography and proton nuclear resonance spectroscopy. PMID- 3330749 TI - A medical microbiology quality assurance programme. PMID- 3330751 TI - [Hemodynamic monitoring in adult respiratory distress syndrome]. PMID- 3330750 TI - The banking and clinical use of human skin allograft in trauma patients: history. PMID- 3330752 TI - Bending the rules: the 2-mu plasmid of yeast. AB - The replication of eukaryotic DNA is normally initiated at each origin only once per cell cycle. Yet, in spite of this restriction, the 2-mu plasmid of yeast has evolved an elegant mechanism which can allow it to rapidly amplify its copy number without initiating multiple rounds of replication. It achieves this by exploiting a plasmid-encoded site-specific recombination system in a way that is apparently unique to this plasmid. The 2-mu plasmid has also evolved a mechanism that allows effective partition of itself between mother and daughter cells. Together these processes ensure the persistence of the 2-mu plasmid within a population, even though retention of the plasmid is of no advantage to the host cell and causes a slightly slower growth rate. The success of this survival strategy is illustrated by the near ubiquity of the 2-mu plasmid in both wild type and laboratory strains of yeast. PMID- 3330753 TI - Use of a beta-lactamase fusion vector to investigate the organization of penicillin-binding protein 1B in the cytoplasmic membrane of Escherichia coli. AB - The coding region for the mature form of TEM beta-lactamase was fused to random positions within the coding region of the penicillin-binding protein 1B (PBP 1B) gene and the nucleotide sequences across the fusion junctions of 100 in-frame fusions were determined. All fusion proteins that contained at least the NH2 terminal 94 residues of PBP 1B provided individual cells of E. coli with substantial levels of ampicillin resistance, suggesting that the beta-lactamase moiety had been translocated to the periplasm. Fusion proteins that contained less than or equal to 63 residues of PBP 1B possessed beta-lactamase activity, but could not protect single cells of E. coli from ampicillin, indicating that the beta-lactamase moiety of these fusion proteins remained in the cytoplasm. The beta-lactamase fusion approach suggested a model for the organization of PBP 1B in which the protein is embedded in the cytoplasmic membrane by a single hydrophobic transmembrane segment (residues 64-87), with a short NH2-terminal domain (residues 1-63), and the remainder of the polypeptide (residues 88-844) exposed on the periplasmic side of the cytoplasmic membrane. The proposed model for the organization of PBP 1B was supported by experiments which showed that the protein was completely digested by proteinase K added from the periplasmic side of the cytoplasmic membrane but was only slightly reduced in size by protease attack from the cytoplasmic side of the membrane. PMID- 3330755 TI - Sensitivity of Escherichia coli to various beta-lactams is determined by the interplay of outer membrane permeability and degradation by periplasmic beta lactamases: a quantitative predictive treatment. AB - In Gram-negative bacteria, beta-lactam antibiotics must overcome two barriers, the outer membrane and the periplasmic beta-lactamase, before they reach the targets of their action, penicillin-binding proteins. Although the barrier property of the outer membrane and catalytic property of the beta-lactamases have been studied and their significance in creating beta-lactam resistance emphasized, the interaction between these two barriers has not been treated quantitatively. Such treatment shows that the sensitivity, to a variety of beta lactams, of the Escherichia coli K-12 cells containing very different levels of chromosomally coded AmpC beta-lactamase, or a plasmid-coded TEM-type beta lactamase, can be predicted rather accurately from the penetration rate through the outer membrane and the hydrolysis rate in the periplasm. We further propose a new parameter, 'target access index', which is a quantitative expression of the result of interaction between the two barriers, and reflects the probability of success for the antibiotic to reach the targets. PMID- 3330754 TI - An 18 amino acid amphiphilic helix forms the membrane-anchoring domain of the Escherichia coli penicillin-binding protein 5. AB - Small (10 residue) C-terminal deletions of PBP5 cause release of this inner membrane protein into the periplasm, indicating disruption of the membrane binding domain. To define the extent of the membrane anchoring domain, oligonucleotide-directed mutagenesis was used to introduce both single amino acid changes and novel restriction sites into the DNA, allowing subsequent construction of precise internal deletions. The 10 C-terminal amino acid residues possess very weak membrane anchoring potential. By extending the sequence to 18 residues membrane binding equivalent to that of authentic PBP5 was achieved. A proline substitution in this region, breaking a potential alpha-helix, also disrupts the membrane binding domain. These results are discussed with respect to the amphiphilicity of the C-terminal sequence when arranged in an alpha-helix. PMID- 3330756 TI - Characterization of the toxicity and cytopathic specificity of a cloned Bacillus thuringiensis crystal protein using insect cell culture. AB - An insecticidal protein gene from Bacillus thuringiensis var. aizawai was cloned in Escherichia coli. The cloned gene expressed at a high level and the synthesized protein appeared as an insoluble, phase-bright inclusion in the cytoplasm. These inclusions were isolated by density gradient centrifugation, the isolated protein was activated in vitro by different proteolytic regimes and the toxicity of the resulting preparations was studied using insect cells grown in tissue culture. The inclusions consisted of a 130 kDa polypeptide which was processed to a protease-resistant 55 kDa protein by tryptic digestion. This preparation lysed lepidopteran (Choristoneura fumiferana) CF1 cells but not dipteran (Aedes albopictus) cells. When the crystal protein was activated by sequential treatment, first with trypsin and then with Aedes aegypti gut proteases, the resulting 53 kDa polypeptide was now toxic only to the dipteran cells and not to the lepidopteran cells. Thus the dual specificity of this var. aizawai toxin results from differential proteolytic processing of a single protoxin. The trypsin-activated preparation was weakly active against Spodoptera frugiperda cells. Membrane binding studies of the trypsin-activated toxin revealed a 68 kDa protein in the lepidopteran cell membranes, which may be the receptor for this toxin. PMID- 3330758 TI - Requirements for transcriptional activation in vitro of the nitrogen-regulated glnA and nifLA promoters from Klebsiella pneumoniae: dependence on activator concentration. AB - Three proteins involved in nitrogen regulation in Klebsiella pneumoniae, NTRA, NTRB and NTRC, have been purified. In a defined in vitro system all three NTR proteins are required for initiation of transcription at the ntr activatable glnA and nifLA promoters. However, in crude S-30 extracts, transcription from the glnA promoter, but not the nifLA promoter, can be activated in the absence of NTRB. A higher concentration of NTRC is required for activation of nifLA transcription than for glnA transcription. Sequences located between -227 and -158 with respect to the nifL transcription start site are required for efficient activation of the nifLA promoter in vitro. PMID- 3330757 TI - ParD: a new gene coding for a protein required for chromosome partitioning and septum localization in Escherichia coli. AB - A new gene, parD, has been located at 88.5 min on the genetic map of E. coli. Cells carrying an amber mutation in this gene, together with a temperature sensitive suppressor tRNA, are able to grow, synthesize DNA and divide at both 30 degrees C and 42 degrees C. At 42 degrees C, however, they are defective both in the separation of replicated chromosomes and in the placement of septa. Both the amount of DNA and the number of septa per cell mass are normal in cells growing at 42 degrees C: only the localization of the chromosomes and septa are altered. As a result, cells of random sizes are produced at 42 degrees C and the smallest of these contain no DNA. PMID- 3330759 TI - Unusual ophthalmological findings in a case of partial trisomy 15. AB - The clinical and pathological findings in a two-month old girl having partial trisomy 15, are presented. The patient showed bilateral microphthalmia accompanied by a retrolental mass in her left eye. She underwent vitrectomy, lensectomy and accidental retinectomy. During the course of the operation, persistent hyperplastic primary vitreous (PHPV) was found with findings of retinal dysplasia on the pathologic examination. PMID- 3330760 TI - Unilateral posterior pole retinoblastoma treated by photocoagulation combined with irradiation and chemotherapy. AB - A 10-month-old baby was referred to our department due to esotropia in the right eye and found to have a large tumor (12 D.D.) in the posterior pole near the optic nerve of this eye. This patient was treated by photocoagulation, irradiation and chemotherapy and satisfactory results were obtained. PMID- 3330761 TI - [Foods and drugs: from the Old to the New World]. PMID- 3330763 TI - [The adolescent and education]. PMID- 3330762 TI - [HIV infection in childhood]. PMID- 3330765 TI - [Sexuality and adolescence]. PMID- 3330764 TI - [Prediction of adult height as response to the health demands of the adolescent]. PMID- 3330766 TI - [Audiologic problems in the first year of life]. PMID- 3330767 TI - Amplitudinal principle for the structural-functional classification of cortical neurons. PMID- 3330768 TI - Systemic mechanisms of higher nervous activity. PMID- 3330769 TI - Current problems in the higher nervous activity of man. PMID- 3330770 TI - Physiology of higher nervous activity as a natural-scientific basis for general psychology. PMID- 3330771 TI - [Early post-infarct angina. Etiopathogenetic, clinical and prognostic factors]. PMID- 3330772 TI - [Medical therapy of early post-infarct angina]. PMID- 3330773 TI - p53 in Paris, an oncogene comes of age. PMID- 3330774 TI - Cloning of tetradecanoyl phorbol ester-induced 'primary response' sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant. AB - The tumor promoter tetradecanoyl phorbol acetate (TPA) is also a potent mitogen for murine 3T3 cells. We have previously described the isolation of variant Swiss 3T3 cell lines unable to proliferative in response to TPA. In this report we sought to identify genes that are stimulated by TPA as 'primary responses', i.e., without intervening protein synthesis. We constructed a cDNA library in lambda gt10, using RNA from quiescent 3T3 cells treated with TPA in the presence of cycloheximide (CHX). Of 50,000 recombinant phages, we identified 50 isolates that demonstrated preferential hybridization to cDNA probes generated from TPA stimulated cells. One of the clones contains a fragment of the proto-oncogene c fos. Twenty-nine of the remaining 49 clones fall into six cross-hybridization families. All the characterized clones detected mRNAs that are also inducible by epidermal growth factor, fibroblast growth factor or elevated serum. TPA induction of all the characterized messages is rapid and transient. All these mRNAs are superinduced by a combination of mitogens and CHX. Induction of these messages following TPA addition also occurs in subconfluent 3T3 cultures; expression of these genes is, therefore, not restricted to the G0/G1 transition. Expression of all six clones was also induced by TPA and other mitogens in 3T3 TNR9 cells, a TPA non-proliferative variant. PMID- 3330775 TI - Anchorage-independent growth of v-myc-transformed Balb/c 3T3 cells is promoted by platelet-derived growth factor or co-transformation by other oncogenes. AB - Murine fibroblasts transformed by the myc oncogene have a reduced growth factor dependence for both anchorage-dependent and anchorage-independent proliferation. Here we show that v-myc-transformed Balb/c 3T3 cells require, in addition to insulin, only platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) for anchorage-dependent growth in serum-free media. PDGF, however, cannot efficiently be substituted by EGF for anchorage-independent growth. The results suggest that constitutive v-myc expression reduces cellular growth factor requirements by non-autocrine mechanisms for proliferation in monolayer cultures. In contrast, v-myc-transformed cells require plasma components and growth factors of the 'competence' type for anchorage-independent growth. We also demonstrate that the requirement for PDGF by the myc-transformed cells can be abrogated by v K-ras, v-src and v-fos but not the v-raf oncogene. The results demonstrate that oncogenes can cooperate in the expression of the transformed phenotype by also drastically reducing cellular growth factor requirements. PMID- 3330776 TI - Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9. AB - Two c-fgr cDNA clones were isolated from a cDNA library derived from a human B lymphocyte cell line, IM-9. Sequence analysis of the clones showed that they contained inserts corresponding to nearly full-length human c-fgr mRNA, which could encode a polypeptide of 529 amino acids with a calculated molecular weight of 59,478. Although the amino acid sequence between Gly-78 and the carboxy terminus of the c-fgr is highly homologous to the corresponding sequence of the c yes protein, the homology between the two proteins is low in the amino-terminal proximal region. Northern blot hybridization analysis using the c-fgr specific sequence showed that the c-fgr mRNA was expressed at higher level in the liver than in the brain, lung, or kidney of a human fetus. PMID- 3330777 TI - c-K-ras mutations in human carcinomas occur preferentially in codon 12. AB - A study was carried out to determine the frequency and distribution of mutations in the c-K-ras gene in human carcinoma tissue. The study was done on a total of 51 lung, colon and breast carcinoma tumors using a panel of oligonucleotides coding for the wild type and all possible mutations in codons 12 and 61 of c-K ras gene. Four of 16 colon carcinomas, two of 27 lung carcinomas and one of eight breast carcinomas were found to contain mutations in codon 12. No mutations were found at position 61. Of the six possible amino acid replacements in codon 12, all but one was represented in the seven mutations identified. PMID- 3330778 TI - Regulation of a metallothionein-rasT24 fusion gene by zinc results in graded alterations in cell morphology and growth. AB - We constructed fusion genes consisting of the mouse metallothionein I (MT) 5' region and the coding region of either the human H-ras gene (c-rasP3) or a mutated allele (c-rasT24); both ras genes lacked the initial (non-coding) exon and the first 30 bp of the non-coding region of the second exon. Transfection of Rat-1 cells produced foci only with pMT-rasT24, and selection in soft agar yielded clones in which MT-rasT24 expression was zinc-regulatable. In response to increasing concentrations of ZnSO4, these lines showed increasingly altered morphology (conversion to fusiform or spheroidal morphology), progressively higher maximal cell density, and an increasingly greater fraction of cells in the S + G2 + M portion of the cell cycle at high density. MT-rasT24 RNA levels in zinc-responsive lines were increased between 4- and 6-fold by the addition of ZnSO4 (final concentration = 100 microM) to the medium. Replating cells in the absence of zinc reversed the biological effects and resulted in reduction in MT rasT24 RNA levels. Thus, graded alterations in phenotype result from increasing levels of MT-rasT24 gene expression. PMID- 3330779 TI - Independently activated dbl oncogenes exhibit similar yet distinct structural alterations. AB - The dbl oncogene was initially isolated following transfection of NIH3T3 cells with DNA of a human diffuse B cell lymphoma. Its transcribed sequences were shown to be distributed over a 30-kb span within a molecularly cloned 45-kb segment of human DNA which contained the transforming gene. By restriction mapping, its transcribed region corresponded to that of its normal allele, except at the 5' end where a rearrangement involved transcribed dbl oncogene sequences from another locus. An independent isolate of a dbl-related transforming gene was obtained following transfection of NIH3T3 cells with DNA of a human nodular poorly differentiated lymphoma (NPDL). Physical mapping indicated that this transforming gene, designated NPDL-dbl, shared considerable homology with the dbl oncogene, but differed at both 5' and 3' termini. Its point of divergence from the normal allele at the 5' end was at least 10 kb upstream from that of the dbl oncogene. The oncogenes each expressed truncated transcripts compared to the 5.3 kb normal transcript. The dbl and NPDL-dbl oncogene translational products of 66 and 76 kDa, respectively, were consistent with their corresponding major 2.8- and 3.5-kb transcripts. It was not possible to detect evidence of the 5' structural rearrangements associated with these oncogenes in either of the original tumors. Thus, if these rearrangements were critical to their activation, they occurred in the process of gene transfer or in vivo in only a minority of tumor cells. PMID- 3330780 TI - Human oncogenes detected by a defined medium culture assay. AB - Oncogenes in DNAs from human tumor cell lines have been detected by a new transformation assay. Cellular DNAs are transfected into NIH3T3 murine fibroblasts, and transformed cells are selected by maintaining cell cultures in a defined medium lacking platelet-derived or fibroblast growth factors. DNAs from eight of 17 human tumor cell lines have yielded transformants by this method. Activated cellular ras genes account for three of the transforming activities. The SAOS2 osteosarcoma cell line contains an activated oncogene distinct from 18 known oncogenes. Another cellular oncogene was detected as the consequence of a fortuitous transfection-mediated DNA rearrangement. PMID- 3330782 TI - The human c-myc exon 1 product: preparation of antisera and analysis of its expression. AB - We investigated the coding capacity of the previously reported open reading frame (ORF) of the human c-myc exon 1. By in vitro translation assay, we found that exon 1 ORF was translated into a 20-kd protein (p20 protein). In order to obtain antisera raised against the p20 protein, we constructed a plasmid vector which expressed most of the exon 1 ORF as a 25-kd (P25) protein in Escherichia coli. Polyclonal antisera raised against this P25 protein specifically precipitated a chimeric protein which contained exon 1-related amino acid sequences. We used these antisera to test for the existence of an exon 1 product in human cells. In the human cell lines tested, these antisera have failed so far to detect any exon 1-related proteins. However, exon 1-related proteins were detected with the anti p20 antisera in quail embryonic cells (QEC) transfected by human c-myc recombinants constructed to express such proteins, but were expressed at low levels compared with the human c-myc protein also expressed in the transfected QEC. Our results suggest that secondary structure of the mRNA could be responsible for the low expression of the exon 1 product in QEC. PMID- 3330781 TI - Isolation and structural analysis of a biologically active chicken c-fos cDNA: identification of evolutionarily conserved domains in fos protein. AB - To identify functionally important domains in the fos gene product we have studied the evolutionary divergence between chicken and mammalian fos proteins. A cDNA containing the entire chicken c-fos coding region was isolated and its nucleotide sequence determined. The deduced 367-amino acid sequence was compared to that of the mouse and human proteins. This comparison revealed a highly conserved domain (98% homology between mouse and chicken) in the center of the protein (85 amino acids) that coincides with a region known to be indispensible for transforming activity. This highly charged domain presumably contains contact sites for DNA and other proteins as well as a nuclear location signal sequence. Two other regions, that are dispensable for transformation, are also highly conserved and may thus be important for the physiological function of c-fos. These are the N-terminal 88 amino acids (85% homology) and the C-terminal 62 amino acids (92% homology). The C-terminus not only contains a potential DNA binding Zn-finger structure but is also the least divergent region in the protein at the nucleotide level (92% conservation between chicken and mouse), supporting the hypothesis that mRNA secondary structures in this region may contribute to post-transcriptional regulatory mechanisms. In contrast, the domains between the terminal sequences and the center region of fos protein show considerable divergence (39% and 45% homology, respectively), indicating a minor role, if any, for these sequences. The significance of these conclusions is emphasized by the observation that the chicken c-fos protein, expressed from the cDNA inserted into a retrovirally-derived expression vector, efficiently induces morphological transformation in rat fibroblasts. The chicken c-fos gene product could be identified by immunoprecipitation and in vitro transcription/translation of the isolated cDNA as a protein of Mr approximately 60 K. PMID- 3330783 TI - ras gene activation in a minor proportion of the blast population in acute myeloid leukemia. AB - DNAs from 22 acute myeloid leukaemia (AML) patients were screened for activated transforming genes using NIH3T3 transfection followed by assay for tumor formation in Nude mice. In four samples an activated N-ras oncogene, and in two samples an activated Ha-ras oncogene were detected in transfectants. Synthetic oligonucleotide probes were used to characterise the mutations in the ras genes. Three samples were found to be mutated to N-ras codon 12 ASP, one to N-ras codon 13 ASP and two to Ha-ras codon 12 VAL. When the corresponding AML DNAs were screened using direct gel hybridisation, the mutant ras genes were detectable in only one case. In two AML samples (82 and 84) with very low percentage blasts (3% and 19%), the absence of mutant ras signal from direct gel hybridisation may be due to the lack of sensitivity of this technique in detecting activated ras in such small fractions of the total DNA. These results illustrate the sensitivity of the in vivo tumour assay in detecting activated ras. When DNA from one of the remaining three AML DNAs was amplified using the polymerase chain reaction method, the mutation present in the transfectant was detected. These findings suggest that even in AMLs with high percentage blasts (40%, 70% and 90%), cells containing mutant ras may comprise only a minor proportion of the major leukaemic clone. PMID- 3330784 TI - The transforming activity of the chicken c-myc gene can be potentiated by mutations. AB - It was previously demonstrated that four different avian v-myc oncogenes harbor several point mutations. At least one of these leads to an amino acid substitution located in the proximity of position 61 in the second exon, whereas additional substitutions are found in exon 3. We have investigated whether these mutations affect the transforming activity of myc. By constructing avian retroviral genomes expressing hybrid gag-myc oncogenes, in which all or parts of the v-myc domains were replaced by corresponding parts of c-myc, we show here that a substitution of threonine 61 of c-myc for a methionine (as in v-mycmc29) significantly enhances the fibroblast transforming capacity of the recombinant oncogene. However, such a hybrid v/c-myc gene is still several fold less active than the v-mycmc29 oncogene. We have also expressed c-myc from subgenomic retroviral mRNAs: in these constructions the AUG of gag in the RNA leader sequence is in the same reading frame as that of c-myc, apparently leading to the production of a myc protein with 11 N-terminal amino acids encoded by gag and non coding c-myc sequences. These myc proteins also transform chicken embryo fibroblasts, albeit with a lower efficiency than v-myc, again suggesting that mutations can increase the transforming capacity of myc. PMID- 3330785 TI - Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. AB - We have examined the genomic organisation of c-myc, N-myc, L-myc, neu and N-ras in tissue from 41 breast carcinomas, lymph node metastases from 10 of these carcinomas, one fibrosarcoma, 10 cases of benign fibrocystic breast and six fibroadenomas. We have not observed an alteration in either N-myc or N-ras in any of the samples studied. We have seen a 2-fold amplification of L=myc in DNA from one infiltrating ductal (ID) carcinoma, but otherwise we have seen no alterations to this gene. Amplification of c-myc was seen in 22% of ID breast carcinoma sample. Levels of amplification ranged from 2- to 10-fold. We have found a significant (p less than 0.02) correlation between an altered c-myc gene and a very poor short-term prognosis. Amplification of neu was seen in 19% of ID breast carcinomas, but the levels of amplification were higher than those seen for c myc. Alterations to neu also correlated well with poor short-term prognosis (p less than 0.0002). Finally, we have observed a low level of amplification of c myc in DNA from a benign fibrocystic breast lesion. This lesion exhibited some features characteristic of those thought to be associated with an increased risk of developing breast cancer. PMID- 3330786 TI - Proto-oncogene fos (c-fos) expression in the heart. AB - Administration of the beta-adrenergic agonist isoproterenol led to a marked rapid increase in the steady-state level of c-fos mRNA in the heart of mice, rats, and Syrian hamsters. Stimulation of c-fos expression by isoproterenol was inhibited by the beta-adrenergic antagonist propranolol. An increase in Ca2+ influx through voltage-dependent calcium channels is probably not required for the activation of the c-fos gene by isoproterenol since the calcium channel blockers verapamil, nifedipine, and diltiazem had no effect on the induction of c-fos by the drug. In the heart of the rat, c-fos expression was also stimulated by the alpha adrenergic agonist phenylephrine, histamine, and prostaglandin E1. The histamine induced expression of the c-fos gene was blocked by the histamine H1-receptor antagonist pyrilamine but not by H2-receptor antagonists ranitidine and cimetidine. It is concluded that in the heart, hormones which increase cAMP and cytosolic Ca2+, such as beta-adrenergic agonists and prostaglandin E1, and/or stimulate the turnover of inositol phospholipids, such as alpha-adrenergic agonists and histamine H1-receptor agonists, regulate c-fos gene expression. The fos protein is likely to play a role in the mechanisms of neurotransmitters and hormones that modulate the functioning of the heart and of cardiac hypertrophy, degeneration and necrosis. PMID- 3330788 TI - Chromosomal localization of the human fyn gene. PMID- 3330787 TI - Common origin of transmissible venereal tumors (TVT) in dogs. AB - We determined the sequence of the 1.5-kb insert upstream to c-myc in the transmissible venereal tumor (TVT) of dogs. The sequence is highly homologous to the 3' region of the mammalian repetitive LINE element. The insert is bound by a 10-bp repeat indicating DNA transposition by a mechanism involving reverse transcriptase. We analyzed DNA of four TVT tumors from various geographical locations as well as normal canine DNA for the presence of the LINE insert. The results indicate that in all TVT tumors, but not in normal tissues, the same LINE insert was present upstream to c-myc. This result suggests that TVT tumors in various dogs may have a common cellular origin. PMID- 3330789 TI - A new anti-p53 monoclonal antibody, previously reported to be directed against the large T antigen of simian virus 40. AB - The PAb1620 antibody belongs to a group of monoclonal antibodies reported to recognize nuclear large T antigen of simian virus 40 (SV40). In the case of PAb1620 there was some indication that the antibody reacted preferentially with large T when it was complexed with p53, the cellular transformation-related antigen. However, we found that PAb1620 does not appear to react with SV40 large T, either free or in complex with p53. In this paper we demonstrate that PAb1620 is, in fact, directed against the p53 protein and recognizes a conformation dependent epitope. In addition, PAb1620 recognises human p53 from SV80 cells. PMID- 3330790 TI - Glycine-cysteine substitution at codon 13 of the N-ras proto-oncogene in a human T cell non-Hodgkin's lymphoma. AB - Tumor-derived DNA from a non-Hodgkin's (T cell) lymphoma patient, assayed by NIH3T3 transfection followed by inoculation of cells into nude mice, was found to contain an activated N-ras proto-oncogene. The mode of activation was determined by hybridization with N-ras-specific oligonucleotide probes detecting mutations at codons 12, 13 and 61. A transversion in codon 13 (GGT----TGT) resulting in replacement of glycine13 by cysteine13 in ras p21 protein was found. The mutation was detected in DNA from mouse tumors induced by transfected NIH3T3 cells and in DNA from patient tumor lymphoblasts. The patient was heterozygous for this mutation. These data identify the first base of codon 13 as a novel mutation site in ras genes and indicate that cysteine at position 13 of the ras p21 is a transforming substitution. PMID- 3330792 TI - [Ultrasonographic findings of hepatic granuloma by Toxocara cati migration]. PMID- 3330791 TI - Currarino syndrome: efficacy of CT. PMID- 3330793 TI - [Comparison of the effectiveness of conventional and intensive insulin therapy in the treatment of diabetes mellitus type 1 in pregnant women or those planning pregnancy]. PMID- 3330794 TI - [Comparison of the effects of chromatographically purified insulin TZF-Polfa and highly purified insulin Nordisk on insulin-induced lipoatrophy]. PMID- 3330795 TI - [Effect of apple pectin on selected indicators of therapeutic control in a group of patients with diabetes mellitus type 2 associated with obesity]. PMID- 3330796 TI - [The placebo phenomenon and its significance in coronary disease]. PMID- 3330797 TI - [Effect of guanfacine on arterial blood pressure and serum lipids and lipoproteins]. PMID- 3330798 TI - [Use of etofibrate in the treatment of patients with hyperlipidemia and arteriosclerosis obliterans of the legs]. PMID- 3330799 TI - [Adrenergic alpha 2 receptor agonists in the treatment of diarrhea]. PMID- 3330800 TI - [Polymer materials for biomedical purposes obtained by radiological methods. I. Review of research trends]. AB - The authors present a review of publications connected with the production of the materials for biomedical purposes using of radiation technology. The general characteristic of the radiation methods and examples of applications of the results of investigations are given. PMID- 3330802 TI - Liver transplantation. PMID- 3330801 TI - Alcoholic liver disease. PMID- 3330803 TI - Current diagnostic tools in the management of gastrointestinal disorders. PMID- 3330804 TI - Fetal medicine and surgery. PMID- 3330805 TI - Newer diagnostic tests and therapies in the management of high risk pregnancies. PMID- 3330806 TI - [Recent status of psychotropic drug therapy]. PMID- 3330807 TI - [Diagnostic imaging of the brain]. PMID- 3330808 TI - [The psychiatrists' opinions with regard to the significance of Pracoxgefuhl in the diagnosis of schizophrenia]. PMID- 3330809 TI - [The two-process model of sleep regulation of Alexander Borbely]. PMID- 3330810 TI - [Selected problems of using current tomographic methods in psychiatry]. PMID- 3330811 TI - [Current concepts of various anxiety disorders: "panic attacks"]. PMID- 3330812 TI - [Possible use of calcium channel blockers in psychiatry]. PMID- 3330813 TI - [Differential diagnosis of depression and dementia]. PMID- 3330814 TI - [The DSM III classification of anxiety disorders in the light of psychological models of anxiety]. PMID- 3330815 TI - [The hospital for mental and neurological disorders at Kochanowka and Lodz in the letters of Prof. Jan Mazurkiewicz to Stefan Zeromski 1902-1907. Contemporary scientific views of Jan Mazurkiewicz]. PMID- 3330816 TI - [Technical preparation for relief impression. Procedure for unaltered impression with movable mouth mucosa]. PMID- 3330817 TI - [Model poured inlay]. PMID- 3330818 TI - [Suction model casting-complete denture]. PMID- 3330819 TI - [Injection technology for slides of cobalt-based alloys. Experimental principles and technical procedures]. PMID- 3330820 TI - [Ergonomic organization and construction of occlusal surfaces with the Sapin System]. PMID- 3330821 TI - [Inlay-/onlay-technic with glass ceramic]. PMID- 3330822 TI - [Technical aspects of the preparation of an implant-supported mandibular complete denture]. PMID- 3330823 TI - [Partial temporary plastic prosthesis--modified preparation procedure]. PMID- 3330824 TI - [Probond technic]. PMID- 3330825 TI - Examining mechanisms of social support and social networks: a review of health related intervention studies. PMID- 3330826 TI - The importance of time in cancer epidemiology: testicular cancer as an example. PMID- 3330828 TI - Effect of low doses of whole body irradiation on spontaneous lung metastasis of NFSA2ALM1 mouse tumors. AB - The effect of low-dose (10-50 cGy) irradiation, delivered as single or fractionated doses, on metastatic development was investigated using NFSA2ALM1 fibrosarcoma and the C3H/HeNrs mouse. Spontaneous lung metastases from tumors transplanted into the leg were suppressed in those mice irradiated with low doses of radiation 12 days after tumor cell inoculation. Abbreviations used: LCFE = lung colony forming efficiency through i.v. injection of tumor cells; SLME = spontaneous lung metastasis efficiency from leg tumors; TD50 = cell number which produces tumors in 50% of inoculated sites; WBI = Whole body irradiation. PMID- 3330827 TI - Therapeutic embolization for renal angiomyolipoma: case report and review of the literature. AB - A 47-year-old woman experienced sudden onset of severe left flank pain. By computed tomography (CT) and arteriography, her condition was diagnosed as a ruptured angiomyolipoma of the left kidney. She did not have tuberous sclerosis. Using polyvinyl alcohol foam (Ivalon) particles, immediate embolization of a main artery feeding the tumor--the posterior branch of the left renal artery--was performed. Three months after embolization, intravenous digital subtraction angiography (IVDSA) showed this main feeder was still occluded. This case and others encountered in our review of the literature underscore the usefulness of therapeutic embolization for renal angiomyolipoma. PMID- 3330830 TI - [Keratocyst of the upper jaw]. PMID- 3330829 TI - Survival of mice and hematopoietic stem cells in bone marrow after intermittent total body irradiation. AB - As a preparative procedure for bone marrow transplantation, intermittent total body irradiation (TBI) has been used in our hospital. The biological significance of this method, in which the instantaneous dose rate is high but the average dose rate is low, has not been evaluated to date. The hematopoietic responses caused by both intermittent and continuous TBI were compared. In the intermittent irradiation, mice in a moving irradiation chamber were exposed under a small field (2 X 35 cm2), and the instantaneous and average dose rates were 1 Gy/min and 0.25-0.12 Gy/min, respectively. The average dose rate was adjusted to the same level in both irradiation methods. LD50/30 and survival of colony-forming units (CFU) in culture and survival of endogenous CFU in the spleen from female BDF1 mice were the same with the two methods. These results show that the response of hematopoietic stem cells depends on the average dose rate, not on the instantaneous dose rate. Our findings suggest that intermittent irradiation, as well as the continuous method, would be useful for preparing patients before bone marrow transplantation. PMID- 3330831 TI - [Mechanical instrumentation in oral rehabilitation]. PMID- 3330832 TI - [Porcelain inlays bonded with light-cured resins]. PMID- 3330833 TI - Circadian rhythms and their application to occupational health and medicine. AB - Detailed measurements of many physiological variables over the course of 24h have indicated that normal human subjects show circadian rhythms. Such rhythmicity derives from an internal clock as well as our rhythmic environment and rhythmic habits. The internal clock is normally adjusted to run with an exact 24-h period by the rhythmic influences in the environment so that, in health, there is a synchrony between the different body rhythms, the internal clock and the external clock. There is evidence that in some individuals such a 'matching' of rhythms does not occur. Further, abnormalities are imposed upon this system after time zone transition and during irregular hours of work (including night work). In all cases, undesirable side-effects are evident in the individual concerned. Where possible, an explanation of these problems is given together with advice that might help to ameliorate them. When applications to medicine are considered, a knowledge of normal circadian rhythmicity can be a diagnostic aid and can, in addition, indicate the most appropriate time for replacement therapy. It is also apparent that the efficacy of drugs can depend upon their time of administration. These aspects of chronopharmacology have most application in the treatment of asthma, arthritis and cancer, all of which are considered in some detail. PMID- 3330834 TI - Blast injury to the ear: a review. PMID- 3330836 TI - Loop diuretics. AB - Loop diuretics such as furosemide, piretanide, and bumetanide bind reversibly to the Na+2Cl-K+ carrier. This transporter is responsible for the uptake of Cl- into the thick ascending limb segment. As a consequence, these compounds reduce or abolish NaCl reabsorption in this nephron segment and lead to a decreased interstitial hypertonicity and thus to a reduced water absorption. Apart from these profound effects, loop diuretics also inhibit Ca2+ and Mg2+ reabsorption in the thick ascending limb in a manner which is still not clear. They also increase urinary K+ excretion by an increase in distal tubule NaCl and water delivery and probably also by the reduction of K+ reabsorption which goes on under in vivo conditions in the thick ascending limb segment. Finally, by the reduction of the transport work in the thick ascending limb, these compounds reduce dramatically the substrate and oxygen dependence of this nephron segment. PMID- 3330835 TI - Ethanol and liver injury: aspects relating to hepatic protein synthesis. AB - Throughout the world ethanol consumption is probably one of the most important and widespread environmental factors in inducing human liver disease. Although it has been established that ethanol is a potent hepatotoxic agent, the mechanism/s by which it acts upon the liver is/are not clear. This review focuses upon one aspect of ethanol and its effect on liver metabolism, that relating to hepatic protein synthesis. Experimental studies have been reviewed and the current views regarding the action of ethanol upon hepatic protein synthesis are presented. The overall picture still remains to be clarified. PMID- 3330837 TI - Thiazide diuretics. AB - Thiazide diuretics increase salt and water excretion primarily by inhibiting mechanisms for electroneutral sodium and chloride transport by distal convoluted tubule cells. This might be termed the 'specific' effect of this class of diuretics and accounts for the 'chlorouretic' effectiveness of the drug. Secondary to this inhibition of sodium and chloride absorption, potassium secretion is stimulated most likely because of the resultant increase in distal tubule fluid flow rate, and calcium absorption is stimulated possibly via a decrease in distal convoluted tubule cell sodium activity and an increase in basolateral sodium/calcium exchange. To a varying degree, thiazides also inhibit carbonic anhydrase. This effect can contribute to the diuresis, but is largely buffered by the reserve transport capacity of the loop of Henle. To the extent that the effects of transport inhibition in the proximal tubule are transmitted to the distal tubule, tubuloglomerular feedback may be activated and effect a reduction in the glomerular filtration rate. PMID- 3330838 TI - 1987 cell-biological interrelationships between short-term and long-term memory. PMID- 3330839 TI - An introduction to molecular approaches in studies of neuronal development and synapse formation. PMID- 3330840 TI - Cholinergic hypothesis of Alzheimer's disease: biophysical aspects. PMID- 3330841 TI - Lesch-Nyhan syndrome: mutation, prevention, and therapy. PMID- 3330842 TI - Myasthenia gravis: a model disorder of acetylcholine receptors. PMID- 3330845 TI - [Medicine and philosophy (XVII)]. PMID- 3330843 TI - An introduction to exocytotic release from nerve terminals. PMID- 3330844 TI - [Current developments in the morphophysiology of the visual analyzer]. PMID- 3330846 TI - [Deceleration of chemically induced genetic mutations in mutant his strains of Salmonella typhimurium]. PMID- 3330848 TI - [The medical world of a century ago]. PMID- 3330850 TI - [Medical implications of the leukotrienes. II]. PMID- 3330847 TI - [Immunotherapeutic properties of medicinal plants. II. Plant immunomodulator macromolecules]. PMID- 3330849 TI - [A manuscript of prescriptions of classical medicine from the 18th century. IV]. PMID- 3330851 TI - [Cryptosporidium and juvenile gastroenteritis]. PMID- 3330852 TI - [Medical centenaries of the year 1987]. PMID- 3330854 TI - Report on group 1 (anti-A) antibodies. PMID- 3330853 TI - Immunohematological study of anti-A monoclonal antibodies of human and mouse origin. PMID- 3330855 TI - Immunohistologic patterns of 32 anti-A monoclonal antibodies in normal human pyloric and duodenal mucosae. PMID- 3330856 TI - Results obtained with 31 monoclonal antibodies (anti-B and anti-A + B) tested for their ability to be used in routine conditions. PMID- 3330857 TI - Immunohistological patterns of 20 monoclonal antibodies against non-A non-B glycoconjugates in normal human pyloric and duodenal mucosae. PMID- 3330858 TI - Tissue distribution of H, Lewis and P antigens as shown by a panel of 18 monoclonal antibodies. PMID- 3330859 TI - Monoclonal antibodies in ABO blood grouping. PMID- 3330861 TI - [Toxicological aspects of exposure to ethylene oxide]. PMID- 3330860 TI - [Experimental study on the possibility of prevention of post-transfusional malaria, by using gentian violet]. PMID- 3330863 TI - Seronegative rheumatoid arthritis in an eight-year longitudinal study. PMID- 3330862 TI - Antinuclear antibodies in lupus erythematosus and Sjogren's syndrome: clinical and immunological investigations. PMID- 3330865 TI - [Protein tyrosine kinase]. PMID- 3330864 TI - Triamcinolone hexacetonide versus betamethasone. A double-blind comparative study of the long-term effects of intra-articular steroids in patients with juvenile chronic arthritis. PMID- 3330866 TI - [Metabolism of phosphatidylinositol and its relation to oncogene-transforming proteins]. PMID- 3330867 TI - [Physiology and pathology of plasma protein C]. PMID- 3330869 TI - [Protein blotting]. PMID- 3330868 TI - [Calcium-binding protein]. PMID- 3330870 TI - [Advances in vascular endothelial cell research]. PMID- 3330871 TI - [Energy-supplying substances and skeletal muscle fatigue]. PMID- 3330872 TI - [Microcomputers and the neurosciences]. PMID- 3330873 TI - [Metallothionein]. PMID- 3330874 TI - [Antioxidative inactivation of enzymes]. PMID- 3330875 TI - [Progress of research on the properties and metabolism of high density lipoproteins]. PMID- 3330876 TI - [Advances in studies of the mechanism of referred pain]. PMID- 3330877 TI - Structure in the precore region of hepatitis B core gene affecting its expression in E. coli. AB - Restriction fragments of HBV-DNA, cleaved by endonuclease HhaI, containing HBcAg gene were trimmed by BAL-31 exonuclease to remove different lengths of the precore sequence. They were inserted into plasmid pUR222 at EcoRI site through synthetic linker ligation. Transformants in E. coli BMH7118 showing different levels of HBcAg gene expression were screened and analyzed for their nucleotide sequences in the junction region both by Maxam and Gilbert's chemical degradation method and by M13 chain termination method. Results of sequence analysis of different transformants revealed a partial palindromic (loop and stem) structure, at -7 to -35 nucleotide with regard to ATG of the HBcAg gene as position +1, which has dramatic effect on the level of expression of the inserted gene using the same promoter, SD sequence and identical N-terminus. The amount of HBcAg synthesized differed from 9% in the high expressing plasmid to less than 0.01% of the total cell proteins in the low expressing transformants. The findings were compared to results obtained by other workers in studies of HBcAg expression in procaryotes and their significance in the expression of eucaryotic genes in procaryotic cells were discussed. PMID- 3330878 TI - [Effects of brain ventricular injection of hypertonic/hypotonic NaCl solutions on plasma renin activity and renal sympathetic nerve activity]. PMID- 3330880 TI - [Remineralization of enamel in permanent and in deciduous teeth after acid etching--a study in vivo]. PMID- 3330879 TI - [Composite acid-etch bridge in the anterior region after 5 years]. PMID- 3330881 TI - [Studies on the indication for primary bone grafting for therapy of mandibular tumors]. PMID- 3330882 TI - [Mechanical mixing of alginate impression material and an efficient method of cleaning the impression trays]. PMID- 3330883 TI - [Metal-sparing bridgework connector construction]. PMID- 3330884 TI - [Impression materials, impression technic, and model preparation for crowns and bridges--a literature review]. PMID- 3330885 TI - [Correcting the fit of cast objects of non-precious alloys with the help of spark erosion]. PMID- 3330886 TI - [Rational attachment for one-piece casting]. PMID- 3330887 TI - [Adhesion of composites under the influence of cavity lacquer]. PMID- 3330888 TI - [Impression accuracy of reversible and irreversible hydrocolloids]. PMID- 3330889 TI - [New ways of functional diagnosis?]. PMID- 3330890 TI - [Prosthetic planning and social indications]. PMID- 3330891 TI - [Histopathological and epidemiological analysis of 343 cases of oral leukoplakia (Venezuela)]. PMID- 3330893 TI - [The judgement of Quevedo]. PMID- 3330892 TI - [Burkitt's lymphoma in Mexico]. PMID- 3330895 TI - The occurrence of natural stable analogues. Implications for the design of therapeutic agents. PMID- 3330894 TI - [Application of spectral analysis to the determination of structures of saccharide moiety in glycosides]. PMID- 3330896 TI - Omeprazole, a new antiulcer drug with a unique mechanism of action. PMID- 3330897 TI - Bambuterol- a prodrug-prodrug with built-in hydrolysis brake. PMID- 3330899 TI - Hyperthermia effect on lipolytic processes in rat blood and adipose tissue. AB - Rats anaesthetized with Brevinarcon were placed in a high-temperature chamber (air temperature 50 degrees C, relative humidity 50%) for induction of hyperthermia (rectal temperature 41.0 +/- +/- 0.5 degrees C). The control group comprised rats anaesthetized in the same way but kept at room temperature. In the serum in both groups glucose, free fatty acids, immunoreactive insulin, lipolytic activity and ability to mobilize lipids in vitro were determined. It was shown that the glucose and free fatty acid levels and the activity mobilizing serum lipids in vitro in the rats subjected to hyperthermia were lower than in the control group by 12%, 23% and 150% respectively. The lipolytic activity of the serum of rats subjected to hyperthermia was 42% higher, and the level of immunoreactive insulin rose by about 224% in relation to the control group. These results point to inhibition of lipolysis in the adipose tissue with simultaneous activation of intravascular lipolysis during hyperthermia in rats. PMID- 3330898 TI - The effect of PGF2 alpha-estrumate on the secretion and composition of abomasal juice in sheep during H2-histaminic receptor blockade with cimetidine. AB - The effect of PGF2 alpha was investigated on the secretion of abomasal juice in sheep after blockade of the H2-histaminic receptor with intravenous cimetidine (150-200 mg). Cimetidine inhibited abomasal juice secretion diminishing juice volume and the content of acid and pepsin in it. During this inhibition intramuscular injection of PGF2 alpha 2.0-4.0 micrograms/kg of body weight caused an increase of these parameters. In control experiments histamine administered (23-28 micrograms/kg) after cimetidine failed to increase the secretion of abomasal juice confirming thus complete blockade of the H2-histaminic receptor. The obtained results demonstrated that the stimulating effect of PGF2 alpha on abomasal juice secretion was not mediated by the H2-histaminic receptor. PMID- 3330901 TI - [The beginnings of the Hospital de las Mercedes]. PMID- 3330900 TI - [The schizophrenic disorder]. AB - The author makes both a historical and up-to-date review of the "schizophrenic defect" concept (S.D.). He comes to the conclusion that this is the "morbid residual" or balance left as "ideo-affective" capital after every productive psychotic outbreak. The S.D. is studied in a "Medium and Long Term" Ward with prevailing statistics amounting to 33% D.E. patients plus 9% active schizophrenic patients over a total average of 100 chronic hospitalized patients. It was found out that 33% of that universe had some scattered family whereas 19% of these patients had no family at all. The latter showed strong tendency towards isolation, slovenliness and "hospitalism". They became "passive-dependent" patients. The situational framework is analyzed. Medical staff relation ships with patients, type of treatment and the illusion created by "fictitious discharge" of E.D. under no favorable psycho-environmental conditions are taken into account. Methods to improve the situation are then outlined and discussed. The following topics are considered: correct therapeutics, family therapy, sectorization, therapeutic community, transition homes (foyers), and current legislation. PMID- 3330902 TI - [Rorschach test and post-traumatic depressive syndromes]. AB - After reviewing the literature on post-concussional syndrome in head injured patients and some studies which have contributed to objectify post-traumatic personality characteristics, the authors were particularly interested in studying depressive signs complained of by such patients without any psychopathological history. The analysis of a group of 47 head injured patients shows that one in two patients openly revealed such depressive tendencies. These patients, who were observed on average less than one year after the trauma, do not differ from the others, whether by age, sex, the severity of the head injury, the existence of a neurosurgical operation. However, they showed many symptoms which were different from those of the other patients in the group and different from those of the whole group. This "depressive" syndrome appears in a more specifically anxious form. The study of the Rorschach's test, on the other hand, does not show any change in the basic personality, especially inhibited in the two groups. For the patients who do not complain openly of depressive signs, the hypothesis of a masked depression was raised. This perspective is compared with the literature's data and allowed to point out several forms of post-traumatic depression. PMID- 3330903 TI - [Association of adrenal pheochromocytoma with metastatic nucleus of ipsilateral renal carcinoma of the clear cell type. Apropos of a case]. PMID- 3330904 TI - [Transversal colonic duct (cutaneous ureterotransversostomy): our experience as a type of urinary derivation]. PMID- 3330905 TI - [Renal oncocytoma: review of the literature apropos of a case]. PMID- 3330906 TI - [Ureteral polyps. Contribution to case material]. PMID- 3330907 TI - [Continent ureteroileostomy. The Kock ileal reservoir: preliminary results]. PMID- 3330909 TI - [Ureteral stenosis in kidney transplant]. PMID- 3330908 TI - [Ureteral obstruction: a complication of surgery of the aorto-ilio-femoral axis]. PMID- 3330910 TI - [Asynchronous bilateral testicular teratocarcinoma]. PMID- 3330911 TI - [Coexistence of multilocular cyst and adenocarcinoma in the same kidney]. PMID- 3330913 TI - Sphincteropathies of the urinary system. PMID- 3330912 TI - [Retroperitoneal liposarcoma in a pre-existing lipoma: presentation of a case]. PMID- 3330914 TI - In vivo activation analysis. I. Classification of available methods and their importance for the clinical use. PMID- 3330915 TI - Barriers to teaching profession for hearing-impaired adults. PMID- 3330917 TI - [Social regulation of delinquent behavior. Theory and research]. PMID- 3330916 TI - Developing hearing-impaired students' writing skills: Martin Buber's mutuality in today's classroom. PMID- 3330918 TI - [The scientific and organizational activities of Prof. Kazimierz Lejman in the field of the history of medicine]. PMID- 3330919 TI - [A short contribution to the history of St. Elizabeth's Church and Hospital in Gdansk]. PMID- 3330920 TI - [Military hospitals organized in the last period of the November Uprising]. PMID- 3330921 TI - [Brother Albert Chmielowski. Psychiatric reflections]. PMID- 3330922 TI - [The Medical Society of Podolia and its library and museum of natural history and pathology 1859-1865]. PMID- 3330923 TI - [The sanitary and nursing services in the Powisle borough of Warsaw during the Warsaw Uprising of 1944]. PMID- 3330924 TI - [The pharmaceutical museums in Poland and throughout the world]. PMID- 3330925 TI - [The evolution of clinical dermatology at the School of Medicine of the University of Wilno in the 19th century]. PMID- 3330926 TI - [The treatment of rabies in Bydgoszcz province during the period of the Grand Duchy of Warsaw (1806-1815)]. PMID- 3330927 TI - [Clinical therapy of tuberculosis in Lodz at the end of the 19th century]. PMID- 3330928 TI - Mutagenic action of phaseolinone, a mycotoxin isolated from Macrophomina phaseolina. AB - Phaseolinone was mutagenic to excision-repair-deficient strains of Escherichia coli WP2 and also to Salmonella typhimurium TA 100. The repair test was indicative of covalent binding of the toxin to DNA. The side-chain epoxide and the hydroxy groups of the molecule were found to be essential for mutagenic activity. PMID- 3330929 TI - Andrew Paul Lawson 1953 to 1987. PMID- 3330930 TI - Obituary: Alan John Grange Mackay. PMID- 3330931 TI - Obituary: Don Urquhart. PMID- 3330932 TI - The Archives of the College. Guide to the History Collection. The D.R. Carter Collection, Parts I, II: H1068-H1139. PMID- 3330933 TI - Spondylolysis: what does this mean? A review. PMID- 3330935 TI - Radiologic manipulation of dislodged Tenckhoff dialysis catheters. PMID- 3330934 TI - Extranodal non-hodgkins lymphoma in rare sites. PMID- 3330936 TI - Autoregulation of glomerular blood flow during converting-enzyme inhibition by captopril. AB - We investigated the effects of local angiotensin-converting enzyme (ACE) inhibition by captopril on the autoregulatory efficiency of glomerular blood flow (GBF). The microvasculature of the nonfiltering rat kidney was observed via in vivo television microscopy. Clamping of the aorta above the renal arteries allowed controlled reductions in renal perfusion pressure. Perfusion pressure reductions (PPR) dilated preglomerular vessels and, within the autoregulatory range, GBF was well maintained. Local captopril application markedly attenuated pressure dependent vasodilation and abolished autoregulation of GBF. Autoregulatory response could be restored in the presence of captopril by adding angiotensin II (A II) to the tissue bath. These results indicate that autoregulation of GBF in the rat kidney is, at least partially, dependent on intrarenal renin-angiotensin activity. PMID- 3330937 TI - Suppression of the plasma aldosterone to renin activity ratio in anaesthetized cats after pharmacological stimulation of the peripheral arterial chemoreceptors with almitrine bismesylate. AB - In chloralosed, non-vagotomized, spontaneously breathing cats the peripheral arterial chemoreceptors were stimulated by intravenous infusion of almitrine bismesylate (Vectarion, 0.20 mg/kg). Within 5 h after administration of the drug, a decline of both the mean systemic arterial blood pressure and the effective renal plasma flow, as well as an increase of the plasma renin activity (PRA) and the plasma aldosterone concentration (PAC) was observed. But as the PAC increase was less than that of PRA, a highly significant suppression of the PAC to PRA ratio was noted. The results indicate that not only whole body altitude hypoxia, but also stimulation of the peripheral arterial chemoreceptors in normoxic animals lowers the PAC-to-PRA ratio. It remains to be verified experimentally whether there exists a specific reflex influence of the peripheral arterial chemoreceptors on the renin-aldosterone relationship. PMID- 3330938 TI - II. International Workshop: Peripheral Arterial Chemoreceptors and Systemic Hypertension. Dedicated to the 100th birthday of Prof. Dr. Dr. Wilhelm Steinhausen. Greifswald, German Democratic Republic, May 25th-29th, 1987. Proceedings. PMID- 3330939 TI - Immunochemical characterisation of the myofibrillar proteinase from cultured rat myocytes as chymase. AB - The proteinase extracted from the myofibrillar fraction of (a) primary rat myocytes and (b) the L-8 myogenic cell line, both maintained in culture, was identified by immunochemical analysis as chymase, the chymotrypsin-like serine proteinase of rat mast cells. Chymase would therefore appear to be an intrinsic protein in the rat myocyte also. PMID- 3330940 TI - Rat hepatocyte lipogenesis and insulin-stimulated lipogenesis: comparison of metabolite effects and methods of measurement. AB - This study compared the effects of certain metabolites (either singly or in various combinations) and the methods of measuring lipogenesis (using either 14C acetate or 3H2O incorporation into lipids) on total lipid synthesis and insulin stimulated total lipid synthesis in the isolated rat hepatocyte. There were quantitative and qualitative differences between 14C-acetate and 3H2O incorporation into lipids; metabolites acutely affected both lipogenesis and insulin-stimulated lipogenesis with either isotope; and insulin's effect on lipogenesis was greater when measured by 14C-acetate incorporation. It is suggested that a particular choice of incubation media and isotope may inadvertently bias a study of insulin-stimulated lipogenesis and that metabolite supply plays a major role in regulating insulin-stimulated lipogenesis. PMID- 3330941 TI - Glucose metabolism "in vitro" in brown adipose tissue from pregnant and lactating rats. AB - (U-14C)Glucose utilization has been studied "in vitro" in brown adipose tissue pieces from virgin, 20-day pregnant and 15-day lactating rats. Brown fat pieces from virgin rats increased their (U-14C)glucose utilization for (14C)CO2 production and for (14C)fatty acid and (14C)glycogen synthesis when insulin was present in the medium. Opposite changes were observed due to the presence of noradrenaline. Brown fat from late pregnant rats does not present any essential alteration in its capacity of metabolizing glucose and showed a pattern of responses to insulin and noradrenaline similar to that from virgins. Brown fat from mid lactating rats showed an intrinsic reduction in (U-14C)glucose utilization for oxidative pathways as well as for fatty acid synthesis, this reduction was present in all hormonal conditions. This data suggests a relationship between the lowered glucose metabolism and the known reduction in brown fat thermogenesis during mid lactation. PMID- 3330942 TI - [Seasonal changes in specific IgE: the acarid Dermatophagoides pteronyssinus]. AB - The authors have studied monthly the titres of specific IgE to Dermatophagoides pteronyssinus, by Phadebas RAST, in 8435 measurements, spread over 4 years. Significant seasonal and monthly variations were seen every year with a maximum level in the autumn or the beginning of winter, with a second peak at the end of winter in 3 years of the 4. There was no close superposition of pattern form one year to another. The domestic relative humidity had a significant effect on the seasonal variation with a mean shift of 2 months that could be explained by the length of the biological cycle of the mites. These data compare with those of the literature (sampling of mites in bedding, longitudinal studies...). PMID- 3330943 TI - [RAST and acari in stored goods]. AB - During a multicentre trial, responses of serum from 60 asthmatic children with allergy to the mite Dermatophagoides pteronyssinus (D1) were compared to D. farinae (D2) and 4 storage mites. The known cross reaction between D1 and D2 was confirmed but no such reaction was found between D1 and/or D2 and the storage mites. Because the important cross reactivity between storage mites, the choice of the allergen will depend on the historical and epidemiological data of the disease. PMID- 3330944 TI - [Determination of histamine]. AB - Introduction of the radio-immunological technique (IMMUNOTECH, Marseille) for the measurement of histamine will in the future facilitate measurement of this mediator and this will be specially interesting during provocation tests for food and drug allergies and for histamine release in anaphylactic accidents caused by hymenoptera venom. The technique is more sensitive than that of the automated fluorimetric analysis. PMID- 3330945 TI - [Immunoscintigraphy, an aid to the oncologist--the Rennes experience in using anti-CEA, anti-CA 19.9 monoclonal antibodies and radiolabelled OC-125]. AB - Immunoscintigraphy is steadily asserting itself as a valuable method in the localization of malignant tumours, alongside other imaging techniques. A monoclonal antibody specific to one or several tumour cell lines is used. The antibody is labelled with a gamma emitter radioisotope and so that it can be detected in vivo. We have evaluated three monoclonal antibodies (F(ab')2 fragments): a mixture of anti-CEA and anti-19.9 antibodies in the investigation of colorectal carcinoma and the antibody OC-125 in ovarian cancer. In our experience, it appears that pelvic recurrence is the best indication for immunoscintigraphy. Antibodies can apparently be safely used in man. We noted no side-effect following the injection of anti-CEA, anti 19.9 and OC-125. PMID- 3330946 TI - Inverse relationship between spontaneous interleukin-1 production and mitogen driven proliferation in patients with pulmonary tuberculosis. AB - The blastogenic response to mitogens of peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers and patients with chronic or acute tuberculosis (TB) was evaluated. Cells derived from TB patients showed a reduced proliferative capacity compared to that of healthy individuals. Three possible causes of such an impairment were investigated, namely: 1) a change in the proportion of lymphocyte subpopulations; 2) an altered ratio between monocytes and lymphocytes and 3) a reduction in the state of monocyte-macrophage activation, with an impaired production of interleukin-1 (IL-1). We observed no significant modification of lymphocyte subsets from TB patients and normal individuals. However, the relative number of monocytes in the patients was always higher than the controls. Furthermore, circulating monocytes from the patients with TB exhibited a decreased phagocytosis of latex beads, a normal expression of DR antigens, and an increased spontaneous production of IL-1. The possibility that the hyperactivation of macrophages may be responsible for the observed low blastogenic response is discussed. PMID- 3330947 TI - [Asthma improved by acetylsalicylic acid]. AB - It is known that in some asthmatic subjects the administration of acetylsalicylic acid (ASA) and non-steroid anti-inflammatory drugs (NSAID) results in bronchodilatation. We have administered 750 mg of ASA intravenously to 100 asthmatic patients who were without history of ASA intolerance. Functional assessment (FEV) was performed under basal conditions and after 5, 10, 15, 30, 60, 90, 120, 150 and 180 minutes after the administration of ASA. 64 patients had no functional variations, 14 showed a percentage variation of less than 20% in FEV and 14 had a doubtful bronchodilatation (FEV 15-20%). The test was repeated after an interval of 1 week in those patients who showed an increase of 20% in FEV and only 2 confirmed the bronchodilatation. The pathogenesis of asthma that is improved by ASA is not entirely clear, but it is an extremely interesting model for study of the role of different mediators in the asthma syndrome. PMID- 3330948 TI - [Hypersensitivity to insects in the agricultural and domestic setting]. AB - The signs of hypersensitivity to insects are frequently seen in general practice and it is clear that it is essential, in order to decide on suitable practice, to know the epidemiological and pathophysiological mechanisms. Specific hypersensitivities that fall into the category of true allergy have a prognosis that may be dangerous and which therefore justify urgent treatment and especially the preventive treatment that has been recognised for the last few years as effective. Non-specific hypersensitivities with secondary symptoms of inflammation may also require preventative action, without resorting to hyposensitisation. PMID- 3330949 TI - [Oral provocation tests (OPT) in the skin pathology of children]. AB - The purpose of oral food challenges is to detect food intolerance. Challenges of food additives and drugs are not often used in children. The authors report methods and protocols that they used for food, food additives and contaminants and emphasize the potential dangers of these tests. Atopic diseases and chronic urticaria are the principal indications. Cow's milk, eggs and fish are the allergens that are most often incriminated. Oral challenges are only to be done as part of an integrated investigation together with skin tests, in vitro tests and a study of intestinal permeability. Food avoidance and therapy should be decided after the challenge data are available. PMID- 3330950 TI - [Allergology and public health]. AB - The authors are reviewing epidemiologic data about the link between the increasing prevalence of allergic diseases and recent changes in way of life all around the world: urbanization, new modes of dwelling, new vegetations, change in environment, parasitosis and infections. PMID- 3330952 TI - [Importance of monitoring peak expiratory flow in the asthmatic patient]. PMID- 3330951 TI - [Immediate allergy,terrain and allergens]. AB - Different backgrounds may be involved in the elicitation of IgE-dependent reactions; an atopic background, i.e. synthesis of specific IgE against common allergens and an allergic background, in the field of drug allergy and allergy to hymenoptera stings, in which atopy is probably not an important risk factor. Allergens have three-dimensional molecular configurations and this is an important determinant of their immunological reactivity. Only multivalent allergens can induce a specific release of mediators. PMID- 3330953 TI - Community participation in New York City: success or failure? AB - This paper describes the planning efforts of a community agency that was ultimately unsuccessful in converting two primary care centers from the traditional fee-for-service Medicaid reimbursement system to a per-capita prepaid Medicaid reimbursement system. We analyze how the community agency prepared its plan, the barriers it encountered in trying to implement a demonstration project, the ambiguous messages community organizations receive from policy-makers, and the role the Mount Sinai School of Medicine played in the conversion effort. PMID- 3330954 TI - Risk factors associated with senile dementia of the Alzheimer's type. AB - Significant cognitive impairment affects approximately 15 percent of the U.S. population over age 65. The most prevalent form of irreversible dementia is senile dementia of the Alzheimer's type (SDAT), which accounts for at least 50 percent of nursing home admissions and roughly 10 billion dollars a year in health care costs. In spite of the social, economic, and medical impact of the disease, epidemiological data are scarce concerning risk factors associated with the disease. Until recently, most of the population-based studies of senile dementia in the elderly were carried out in Northern European countries. The methodological problems that arise in performing epidemiologic studies on SDAT may in part explain the lack of sufficient data pertaining to certain risk factors. This paper provides a review of the literature and research on risk factors in dementia in the elderly and discusses directions for future research. The epidemiological issues associated with certain key studies are also discussed. Although the major studies that have attempted to look at risk factors in mental illness in the elderly are beginning to fill in some of the gaps in the understanding of the etiology and epidemiology of the disease, further epidemiologic studies on both institutionalized and community-based elderly populations are needed. These should assess a wide range of possible factors (demographic, psychological, environmental, health practice, and medical) in terms of their association with SDAT. By developing a comprehensive epidemiologic profile of SDAT, possible preventive measures and therapeutic approaches to treating the disease may be identified and hypotheses for future epidemiological and laboratory investigations developed. PMID- 3330955 TI - Expert systems: frames, rules or logic for species identification? AB - The role of expert systems in species identification, with particular reference to the problems posed by damaged specimens and inexperienced taxonomists, is discussed. Of the three main types of expert systems available, the frame-based system is shown to provide the most appropriate model for a taxonomic expert system rather than a logic- or rule-based system. The advantages of an expert system over other computer-aided methods of identification are considered. A rule based system requires the original knowledge (species descriptions) to be structured into rules, whereas a frame-based system can store the generic and specific descriptions in a series of frames. The frames fall into a hierarchy which closely resembles the taxonomic hierarchy, and down which information can be inherited. Two aspects of frame-based systems considered are the use of probabilities in identification, and the optimum structure of the knowledge base. The conventional use of probabilities is to provide an indication of the correctness of the result. However, in some studies involving the identification of many specimens, the speed of identification may be increased (with a reduction in accuracy) if identifications are made to a predetermined probability level. Although frames allow accurate representation of the taxonomic hierarchy, a semantic net, incorporating structures of the organism and/or details of the habitat may result in a more efficient expert system. PMID- 3330956 TI - A microprocessor-based control unit for Plasmodium falciparum culture apparatus. AB - We describe a microprocessor-based control unit for apparatus which effects changes of culture medium on Plasmodium falciparum parasites maintained in vitro. The unit has required minimal attention during the two years it has been in operation and it has markedly facilitated the production of mature sexual stages of Plasmodium falciparum on a routine basis. PMID- 3330957 TI - Repetitive palindromic sequences in Escherichia coli. Detection and characterization with a new computer program. AB - We have made use of a new computer program which rapidly searches for DNA patterns irrespective of the exact sequence, in order to search systematically for repetitive palindromic structures on the Escherichia coli chromosome. By using a relatively restrictive criterion, we detected three families of palindromic structures. One is present in ribosomal RNA operons. Since seven identical ribosomal RNA operons are found on the E. coli genome, this constitutes a validation of the method. Another family is constituted by the extragenic palindromic units (PUs or REP) already described (Gilson et al., 1984). We propose a slightly different consensus for this highly repetitive and dispersed family. The last is a subclass of symmetrical transcription termination sites which we have identified. They are present in four attenuator sites and at least one terminator for convergent operons. We suggest that these symmetrical terminator sites may play a general role in the termination of transcription for convergent operons. We discuss briefly how this type of approach could be used to analyse the structure of genomes. PMID- 3330958 TI - Two different approaches to computer-aided teaching of microbial genetics. AB - Two computer packages have been developed to teach bacterial genetics on an introductory genetics course for undergraduate students in biology. The first package, 'CONJUGACION', is designed to teach bacterial conjugation and its genetic outcomes. It includes four main parts. Firstly, a tutorial part presents a theoretical framework using screens of text and animated graphics. Secondly, an interactive concept application section requires students to carry out experiments for the determination of the correct sex and genotype of 10 bacterial strains. The third part uses the previously obtained data for simulating interrupted mating experiments and mapping the bacterial genome. Finally, an evaluation section allows the students to test their understanding through a series of multiple choice questions. The second package, 'LURIDEL', is intended for teaching the preadaptative character of mutation in bacterial populations on the basis of the fluctuation test of Luria and Delbruck. It simulates, graphically, the appearance of mutations in microbial cultures and gives results of simulated fluctuation experiments. Programs were written under the PCOS operating system in MBASIC extended to graphics for running on Olivetti M20 microcomputers. PMID- 3330959 TI - An algorithm for discriminating sequences and its application to yeast transfer RNA. AB - We describe an algorithm for finding nucleotide residues strongly correlated with the amino acid acceptor functions of transfer RNAs. The algorithm exploits the fact that each tRNA accepts only one of 20 amino acids. The algorithm is applied to 37 Saccharomyces cerevisiae transfer RNAs. PMID- 3330960 TI - Recognition of characteristic patterns in sets of functionally equivalent DNA sequences. AB - An algorithm has been developed for the identification of unknown patterns which are distinctive for a set of short DNA sequences believed to be functionally equivalent. A pattern is defined as being a string, containing fully or partially specified nucleotides at each position of the string. The advantage of this 'vague' definition of the pattern is that it imposes minimum constraints on the characterization of patterns. A new feature of the approach developed here is that it allows a 'fair' simultaneous testing of patterns of all degrees of degeneracy. This analysis is based on an evaluation of inhomogeneity in the empirical occurrence distribution of any such pattern within a set of sequences. The use of the nonparametric kernel density estimation of Parzen allows one to assess small disturbances among the sequence alignments. The method also makes it possible to identify sequence subsets with different characteristic patterns. This algorithm was implemented in the analysis of patterns characteristic of sets of promoters, terminators and splice junction sequences. The results are compared with those obtained by other methods. PMID- 3330961 TI - Microcomputer package for statistical analysis of microbial populations. AB - We have developed a Pascal system to compare microbial populations from different ecological sites using microcomputers. The values calculated are: the coverage value and its standard error, the minimum similarity and the geometric similarity between two biological samples, and the Lambda test consisting of calculating the ratio of the mean similarity between two subsets by the mean similarity within subsets. This system is written for Apple II, IBM or compatible computers, but it can work for any computer which can use CP/M, if the programs are recompiled for such a system. PMID- 3330962 TI - Pediatric head injury. PMID- 3330963 TI - Prognostic indicators in patients with severe head injury. PMID- 3330964 TI - Leptospirosis in horses in Ontario. AB - Sera from Thoroughbred and Standardbred horses in southwest Ontario were tested for antibody to seven Leptospira interrogans serovars (autumnalis, bratislava, canicola, grippotyphosa, hardjo, icterohaemorrhagiae, pomona), using the microscopic agglutination test. There was significantly higher seroprevalence of bratislava than of other serovars, in which prevalence was low. Seroprevalence of bratislava increased significantly with age; only 5% of two to three year old horses had titers greater than or equal to 1:80 compared to 52% of horses older than seven years. Eight of 16 foals from two farms seroconverted at low titers to bratislava between four and eight months of age. Leptospires were not detected by immunofluorescence and isolation techniques in 50 kidneys collected from horses at slaughter. Fetal tissues from 52 aborted horse fetuses were also examined by these methods and serovar kennewicki was identified by immunofluorescence and by isolation in one fetus. Serovar bratislava appears to be widespread in horses in Ontario but unimportant in abortion. The clinical significance of this infection in horses in Ontario is unclear. PMID- 3330967 TI - Syngrafting skin among mice of similar and different ages increases the number of Langerhans cells and decreases responsiveness to 1,4-dinitrofluorobenzene. AB - Counting on suction blister skin biopsies, the number of Langerhans cells per mm2 in BALB/c mouse epidermis was found identical in 1-, 11-, and 22-month-old animals, but consistently elevated in syngrafted skin 10 months after transplantation. This effect of grafting was independent of whether young or old skin was transferred to young or old recipients. Skin swelling induced by dinitrofluorobenzene (DNFB) sensitization was reduced in 22-month-old non-grafted mice and in grafted skin irrespective of donor and recipient age. PMID- 3330965 TI - Safety and immunogenicity of a vaccine bait containing ERA strain of attenuated rabies virus. AB - Ninety percent of foxes fed commercial ERA vaccine in a specially designed bait developed rabies serum neutralizing antibodies. The vaccine bait did not cause clinical signs of rabies when consumed by foxes, raccoons, skunks, dogs, cats, cattle and monkeys. When presented, in the laboratory, to wild rodents of the species Microtus, Mus musculus and Peromyscus, the vaccine baits caused vaccine induced rabies only in Mus musculus. Laboratory mice of the CD-1 and CLL strain were susceptible to vaccine-induced rabies; however, studies showed that transmission of virus to other animals did not occur. These studies suggest that the vaccine bait described could be useful in a rabies control program in areas where foxes and wild dogs are the principal vectors. PMID- 3330968 TI - [1986 is dead. Long live 1987!]. PMID- 3330966 TI - Pulmonary bacterial deposition and clearance during ascarid larval migration in weanling pigs. AB - Pulmonary deposition and clearance of bacteria were measured in weanling pigs, half of which had been inoculated at age 31 days with larvated Ascaris suum ova. Seven days later, when breathing signs of larval migration were pronounced, all pigs were exposed to aerosolized Escherichia coli (strain B). Then, either immediately after aerosol exposure (for deposition assessment) or immediately after a 120 minute period in filtered air (for clearance), bacteria in the pigs' lungs were counted. Ascarid ova-inoculated pigs did not differ significantly from control pigs for number of bacteria in the lungs after aerosol exposure, but after the 120 minute clearance period they had 7.2 times more than did the control pigs. Thus, in weanling pigs, the breathing-pattern changes that were evident during ascarid-larval migration did not affect pulmonary deposition of inhaled bacteria significantly, but the presence of ascarid larvae in the lungs was associated with impaired pulmonary bacterial clearance. PMID- 3330970 TI - [Treatment of blepharospasm: medical or surgical?]. PMID- 3330969 TI - [Brunstig Perry syndrome. Apropos of a case]. PMID- 3330972 TI - [Astigmatism and keratoplasty]. PMID- 3330971 TI - [Fluorophotometry and the corneal endothelium: preliminary results]. PMID- 3330973 TI - [Preoperative evaluation of radial keratotomy]. PMID- 3330975 TI - [Cystic hamartoma of the hepatic pedicle in the adult. A case and review of the literature]. PMID- 3330974 TI - [Current role of Kock's continent ileostomy]. PMID- 3330977 TI - [Congenital cystic dilatation of the common bile duct. Reflections apropos of 8 cases]. PMID- 3330976 TI - [Heart injury caused by a bullet. Migration of the projectile into the right subclavian artery]. PMID- 3330978 TI - [Surgical treatment of mandibular ameloblastoma with preservation of the neurovascular bundle and bone graft]. PMID- 3330979 TI - Medical student attitudes toward the elderly: a critical review of the literature. PMID- 3330980 TI - Bullous ichthyosiform erythroderma--a case report. PMID- 3330981 TI - Dermatomycosis in Udaipur region (Rajasthan). PMID- 3330982 TI - Observations on nasal late phase reactions. PMID- 3330983 TI - Indirect immunoperoxidase test in the diagnosis of rabies. PMID- 3330984 TI - Transverse sectioning of plastic-embedded immunolabeled cryosections: morphology and permeability to protein A-colloidal gold complexes. AB - In order to provide data for meaningful interpretation and quantitation of immunogold labeling on cryosections their morphology and permeability to protein A-gold were evaluated: We studied plastic sections of immunogold-labeled ultrathin and semithick cryosections cut perpendicular to the original cryosection plane. Various soluble and insoluble antigens in different specimens (hemoglobin and histone H5 in chicken erythrocytes, tubulin in Leishmania cells, and outer membrane protein OmpA in Escherichia coli) were fixed with glutaraldehyde-formaldehyde, formaldehyde, or periodate-lysine-paraformaldehyde and incubated with specific antibodies and protein A-gold of different sizes. The cryosection surface may be rough or smooth depending both on the sectioned material and on dehydration and drying artifacts or possibly on the cutting process itself. Well-preserved sections are capable of withstanding considerable deformation without showing clefts or cracks. If the sectioned specimen is sufficiently fixed, protein A-gold is not able to enter the IgG-labeled sections significantly but follows surface irregularities. However, gold particles can be detected within visibly damaged sections. PMID- 3330985 TI - Serum zinc is unaffected by effective captopril treatment of hypertension. AB - Captopril, a sulfhydryl compound that lowers blood pressure by inhibiting the zinc metalloenzyme, angiotensin converting enzyme, may occasionally result in ageusia, a symptom also associated with zinc deficiency. We therefore studied serum zinc and copper concentrations in a group of 14 essential hypertensive subjects before treatment and after 5-6 months of antihypertensive oral monotherapy with either captopril (50 mg, twice daily; n = 7) or other drugs (propranolol or alphamethyldopa; n = 7). Serum zinc and copper were unaltered by either regimen. Thus, zinc depletion is an unlikely consequence of long-term exposure to captopril, at least in the dosages commonly used for treatment of hypertension. PMID- 3330986 TI - Comparison of antihypertensive, renal hemodynamic, and humoral effects of pinacidil and hydralazine monotherapy. AB - The antihypertensive, renal hemodynamic, and humoral effects of pinacidil and hydralazine monotherapy were compared in a double-blind study. Supine diastolic blood pressure decreased with pinacidil (n = 14) from 96.5 to 82.6 mmHg (p less than 0.05), after a mean of 8.5 weeks at a mean dose of 64.3 mg/day, and with hydralazine (n = 15) from 101.5 to 94.0 mmHg (p less than 0.05), after 8.3 weeks at a dose of 163.3 mg/day. Renal plasma flow, glomerular filtration rate, and urinary albumin excretion did not change with pinacidil or hydralazine therapy. Neither agent altered plasma renin activity. Supine and upright plasma aldosterone concentrations decreased significantly during pinacidil, but not during hydralazine, therapy. Thus, both pinacidil and hydralazine reduced blood pressure and preserved renal function. During pinacidil therapy, plasma aldosterone concentrations decreased, whereas plasma renin activity did not. The mechanism of this response is unclear. PMID- 3330987 TI - Antihypertensive efficacy of sustained-release verapamil. AB - The antihypertensive effects of immediate-release (IR) verapamil were compared with those of sustained-release (SR) verapamil in 58 patients. After an open label (IR verapamil) study, patients were randomized into a double-blind study to continue receiving the same dose of IR verapamil three times daily or an equivalent dose of SR verapamil (240 to 480 mg) once daily. Blood pressure decreased from 149/98 to 139/90 mmHg (p less than 0.01) with IR verapamil and from 150/98 to 136/88 mmHg (p less than 0.01) with SR verapamil. Ambulatory blood pressure monitoring showed a similar response for the two formulations. Diastolic pressure was less than 90 mmHg in approximately 67% of the IR verapamil group and 61% of the SR verapamil group. Mean trough plasma concentrations of verapamil were 70 and 59 ng/ml at 2 and 4 weeks, respectively, after treatment with IR verapamil; the corresponding values were 70 and 94 ng/ml for the SR verapamil group. SR verapamil administered once daily is an effective antihypertensive medication in a selected group of patients and could afford better compliance. PMID- 3330988 TI - Double-blind, placebo-controlled trial of twice-daily nifedipine as a step-2 agent in mild essential hypertension. AB - Nifedipine is a calcium-channel blocker that produces vasodilatation and decreased peripheral resistance in humans. Several clinical reports document blood-pressure-lowering effects of nifedipine with either acute or chronic administration. Little data are available to evaluate sustained-release nifedipine as a step-2 agent. We performed a multicenter double-blind, placebo controlled trial of twice-daily nifedipine in the treatment of mild essential hypertension not controlled by diuretic alone. Seventy-one subjects completed 8 weeks of treatment with nifedipine or placebo in combination with a stable dose of diuretic. Treatment groups were comparable with respect to age, sex, race, duration of hypertension, and pretreatment weight. Baseline supine blood pressure was no different in the two treatment groups (144 +/- 15/98 +/- 6 mmHg in the nifedipine/diuretic-treated group and 145 +/- 16/98 +/- 6 mmHg in the placebo/diuretic-treated group). After 8 weeks of treatment, supine blood pressure was 132 +/- 11/88 +/- 6 mmHg in the nifedipine/diuretic-treated group and 140 +/- 16/92 +/- 8 mmHg in the placebo/diuretic-treated subjects (p less than 0.01 for both systolic and diastolic blood pressure when compared to placebo/diuretic). Nifedipine with diuretic had similar effects on standing blood pressure. Nifedipine/diuretic decreased blood pressure from baseline values within 1 week of treatment, and the effect persisted for 8 weeks. Heart rate increased in nifedipine/diuretic-treated subjects during the first 2 weeks of treatment but returned to baseline by 4 weeks. No laboratory abnormalities could be attributed to nifedipine/diuretic treatment. Side effects were mild and infrequent. In summary, nifedipine/diuretic is effective and well tolerated in the treatment of uncomplicated essential hypertension inadequately controlled with diuretic therapy alone. PMID- 3330989 TI - Comparative effects of pinacidil and prazosin on blood pressure, weight, plasma volume, the renin-angiotensin-aldosterone system, and the renal kallikrein-kinin system in patients with essential hypertension. AB - Patients with essential hypertension were randomized to treatment with either prazosin or pinacidil, a new direct-acting vasodilator. Factors that might modulate the antihypertensive response and result in pseudotolerance to these drugs were measured before initiation of therapy and following 12 weeks of treatment. Despite significant reductions in blood pressure, pinacidil and prazosin did not produce an increase in plasma volume, did not activate the renin angiotensin-aldosterone system, and did not interfere with the renal kallikrein kinin system. The data fail to reveal evidence of physiologic compensatory changes that would lead to the development of pseudotolerance. PMID- 3330990 TI - Combined effects of sex and hypertension on the geometrical design of large arteries. Sexual differences in normal and hypertensive forearm arteries. AB - The effects of sex, hypertension, morphological status, and heart rate were assessed on the large arteries of 46 normotensive subjects (23 men and 23 women) and 50 hypertensive patients (25 men and 25 women) by means of pulsed Doppler determination of diameter and blood velocity of the brachial artery. Compared with men, women had lower height, weight, and forearm volume (p less than 0.001), higher heart rate (p less than 0.001), and lower brachial artery diameter (p less than 0.001), both in the normotensive and hypertensive groups. Compared with normotensive subjects, hypertensive patients of the same sex showed an increase in brachial artery diameter (only significant in men [p less than 0.001]) and an increase in heart rate (only significant in women [p less than 0.001]). The multiple regression analysis of brachial artery diameter showed significant coefficients for sex and hypertension (p less than 0.001) and for age and heart rate (p less than 0.05); the multiple regression analysis of blood velocity showed that only coefficient of hypertension was significant (p less than 0.05). The study of first-order interactions between the independent variables revealed that effect of sex on arterial diameter did not depend on the other variables. In contrast, the effects of age and heart rate were influenced by the presence or the absence of hypertension, and arterial caliber was positively related to age in normotensive subjects (p less than 0.05) but not in hypertensive patients and negatively related to heart rate in hypertensive patients (p less than 0.01) but not in normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3330991 TI - Acute hemodynamic action of captopril in congestive heart failure: contrasts between refractory and untreated patients. AB - To compare the hemodynamic mode of action of captopril in patients with Congestive Heart Failure (CHF) with high- or low-plasma renin activity, we studied the systemic and renal hemodynamic changes induced by this drug in patients with refractory CHF (Group I) or untreated CHF (Group II). Plasma Renin Activity (PRA) was 7.46 +/- 3.7 ng/ml/hr in Group I and 1.15 +/- 0.45 ng/ml/hr in Group II. After the administration of captopril, these values increased to 14.35 +/- 6.19 and to 1.99 +/- 0.76 ng/ml/hr respectively (p less than 0.05). We observed that patients of Group I responded with increases in cardiac index and stroke volume and diminutions in total peripheral resistance, but Group II did not show any significant change in these variables. In contrast to this difference in responses between the refractory and untreated patients, both groups showed similar decreases in pulmonary artery and wedge pressures. Both groups also showed similar increases in plasma volume and effective renal plasma flow, and decreases in renal vascular resistance. These results show that captopril has predominantly venodilator effects in patients with CHF with low PRA levels, and it acts as a mixed vasodilator in patients refractory to conventional therapy, receiving high doses of diuretics, and in whom PRA is elevated. Our results also suggest that the venodilator action of captopril is not mediated by the Renin-Angiotensin System. PMID- 3330992 TI - Nifedipine GITS and hydrochlorothiazide in essential hypertension. AB - Twenty-nine subjects with mild to moderate essential hypertension completed this 13 week randomized, double-blind, placebo-controlled study comparing the antihypertensive effects of nifedipine GITS (N) (30-60 mg/day), hydrochlorothiazide (H) (25-50 mg/day) and placebo (P). Nifedipine GITS is a new formulation designed for once daily administration. N lowered blood pressure 15/10 mmHg (p less than 0.0005/p less than 0.0001), H 15/8 mmHg (p less than 0.0005/p 0.05), and P 4/0 mmHg (p = NS). All patients required the larger dose of active drug to control BP. No drug affected the heart rate. For N, but not H, there was a positive correlation between age and the magnitude in reduction of SBP (r = 0.79; p less than 0.005), but not for DPB. N drug levels did not correlate with its antihypertensive effect. Epinephrine, norepinephrine, aldosterone, and plasma renin activity were not affected by N. No patients on N experienced immediate vasodilator side effects. N is a well tolerated and effective antihypertensive drug that can be given once daily. It does not cause reflex stimulation of the sympathetic nervous system. PMID- 3330994 TI - Physical structure of winter sports athletes. AB - A review of the results concerning the body size, growth, maturation, shape, composition, and strength of ice hockey players, cross-country skiers, alpine skiers, ski jumpers and Nordic combined skiers is presented. The comparisons of the results in body height, weight, somatotypes, percent fat, LBM and hand grip from various authors are made. Also the differences between ice hockey players and skiers of all disciplines are shown. The review covers all the available results. It may be concluded that the elite athletes in each studied sport form a highly select group which has, from the biomechanical point of view, the best physical structure for their sport discipline. PMID- 3330995 TI - The narcissism and death of Yukio Mishima--from the object relational point of view. AB - The author discussed the life and work of Yukio Mishima from the object relational point of view. First, he described his brief life history, pointing out the four big identity crises in his life as his fierce struggles against the suicidal wishes were likely to enlarge within himself. Then, he suggested that Mishima had been in the state of part object relationship throughout his life. Thirdly, the important role of the body or bodies in his fantastic and real life was discussed as a manifestation of not merely autoerotic activities but also disturbances of the core of identity. Finally, the fragility of the intermediate area of experience which was thought to have eventually led him to the last action, the seppuku, was examined. PMID- 3330993 TI - Amikacin-acetyltransferase (AAC-6'/I) encoded by an IncH2 plasmid (pIE866) in Escherichia coli strains. AB - An amikacin resistance plasmid was detected in E. coli wild type strains isolated from polluted surface water. This conjugative 145 Md plasmid belongs to the IncH2 group and specifies amino-glycoside-acetyltransferase AAC-6'/I activity. PMID- 3330996 TI - Serial polysomnograms in Creutzfeldt-Jakob disease. AB - This is a report of the case of a patient with Creutzfeldt-Jakob disease, whose electroencephalograms and polysomnograms were repeatedly recorded throughout the course of the illness with details of the alterations of periodic synchronous discharges. In the advanced stage of the disease, the appearance of peculiar paroxysms was noted, predominantly in the early morning. Furthermore, apnea of the central type was observed during the same time period. Discussions were held on the mechanisms inducing the EEG paroxysms and apneas. PMID- 3330997 TI - Cell-surface markers on haemopoietic precursors. Reagents for the isolation and analysis of progenitor cell subpopulations. AB - Within the last decade, major advances have been made in the analysis of cell surface marker expression on haemopoietic progenitor cells as a result of the development of multiparameter cell sorting and monoclonal antibody techniques. Although some controversy exists with regard to the actual identification of the stem cell, markers specific for CFU-s and for particular subsets of progenitor cells have not yet been identified. An analysis of cell-surface markers on haemopoietic progenitor cells is complicated by at least three factors. First, it appears that, in mice, the clonal assays do not adequately identify the haemopoietic stem cell. Complete repopulation of all haemopoietic cell compartments in vivo over an extended period of time appears to be the only reliable method for identifying such a cell. Secondly cell-surface marker distribution on haemopoietic progenitors from normal tissues may be indicative of the cycling status of cells. Thus, expression of markers on progenitors from bone marrow or foetal liver which have been perturbed by drugs or viruses may merely reflect a change in their cycling status following drug or viral insult. Thirdly, substantial loss of cells occurs during the purification of particular cell types. For most cell separation procedures, only a minor proportion of the progenitor cells of interest are recovered and these may not be representative of the progenitor population as a whole. During differentiation to mature cells, antigenic determinants present on early progenitor cells may either be progressively lost or amplified. This differential expression of cell-surface molecules has provided a useful tool for the substantial enrichment of haemopoietic subsets, particularly CFU-E and CFU-s. To date, however, most early haemopoietic progenitor cells detected by in vitro CFC assays (day 8 CFC) cannot be completely segregated from one another. The ability to distinguish between such progenitors during the early stages of lineage commitment would provide a more detailed understanding of the relationship between lymphoid precursors, myeloid precursors and stem cells, and would lead to significant advances in developmental biology. Separation of cells at different stages of differentiation within a given lineage would provide an opportunity for studying regulatory mechanisms involved in gene expression in normal cell populations. PMID- 3330999 TI - The war's most incredible document. PMID- 3330998 TI - Immunohistochemical localization of c-erbB-2 in human breast carcinomas. AB - This study was carried out to assess the utility of antibodies raised to synthetic peptides of the predicted sequence of the c-erbB-2 gene product to identify immunocytochemically those tumours overexpressing this putative transmembrane receptor. Staining with rabbit antiserum 21N gave the best correlation with gene amplification and did not stain the membrane of any of the normal tissues at the dilution which strongly stained the membrane of any of the normal tissues at the dilution which strongly stained the amplified tumours. No significant correlation was found with lymph node involvement, epidermal growth factor receptor status or with oestrogen receptor levels. Of the 12 out of 34 cases which demonstrated c-erbB-2 gene amplification in the primary tumour, two had lymph node metastases which were also positive immunocytochemically. Fourteen other cases which had lymph node metastases were negative in the primary tumour and in the metastases. These tumours all showed strong membrane positivity. A comparison of modified methacarn and formol saline fixation demonstrated an increased sensitivity with the former, but the staining pattern was unaltered. This small but extensively studied group of cases has indicated that increased c erbB-2 protein can be identified routinely in fixed tissue sections, making it possible to carry out extensive studies to look for clinical correlates, but also to assess the stage in tumour progression at which the increased expression occurs and whether it correlates with any potentially premalignant condition. PMID- 3331000 TI - Drugs as tools for research in neuropsychobiology: a historical perspective. AB - Knowledge in neuropsychobiology continues to benefit from the use of drugs as 'tools' to alter neurochemical events as a means of studying interactions between the events and behaviour. Before drugs could play such a role, concepts about basic properties of living organism had to be refined. Techniques had to be invented for investigating the kinetics by which drugs reach their sites of action within the body and the dynamics of their effects once they have occupied their receptors, behaviour being one category of such effects. The present discussion examines these developments in historical perspective, focusing upon influences they have in advancing our understanding of neurochemical substrates of behaviour. PMID- 3331001 TI - Intraarticular corticosteroids in treatment of osteoarthritis. AB - The history of the use of intraarticular corticosteroids in the treatment of osteoarthritis and the various available corticosteroid preparations, their possible mechanism of action, side effects, and results of treatment are presented. The longest-lasting effects in the alleviation of joint symptomatology are produced by the tertiary-butyl acetate esters of the various corticosteroid preparations. The effect produced by triamcinolone appears to be of the longest duration. The anti-inflammatory action of corticosteroids seems to be responsible for the alleviation of joint symptomatology in osteoarthritis. Significant adverse effects, such as steroid arthropathy and tendon rupture, may result from excessive intraarticular use. Infection is an uncommon complication when adequate skin preparation is performed. The major disadvantage of intraarticular corticosteroids is their short duration of action, averaging two to three weeks. However, a small percentage of patients with osteoarthritis may sustain prolonged relief from one or two injections. Acute self-limited disorders, such as trigger finger and inflamed bursae, seem to lend themselves best to this form of therapy. PMID- 3331002 TI - The role of open surgery for patellofemoral joint malalignment. AB - The authors outline their philosophy in the treatment of acute patellofemoral dislocation and chronic subluxation and dislocation of the patella. They note that while nonoperative treatment is used most often and is most often successful, surgical management also has a role. They outline their rationale for surgery. PMID- 3331003 TI - Protrusio acetabuli prosthetica. AB - Protrusio acetabuli prosthetica is a form of hip replacement failure in which intrapelvic component migration occurs. Three degrees of the entity are defined as determined by (1) prosthetic migration medial to the ilioischial line and (2) integrity of the medial acetabular wall. Entities predisposing to protrusio acetabuli prosthetica include overreaming, multiple pelvic perforations, osteopenic bone states, infection, trauma, heredity or acquired bone deficiency states, overactivity, and hypertrophic membrane formation. Treatment of the condition is contingent upon (1) reestablishment of the radiographically determined anatomic position of the acetabulum and (2) construction of a medial prosthetic or biologic buttress. Recent techniques of biologic medial-wall formation utilize either allograft or autograft bone in one of three configurations--bulk, chipped or pulverized. In cases of severe intrapelvic hip protrusion, resection arthroplasty may be the only alternative. PMID- 3331005 TI - Salmonella osteomyelitis after internal fixation of fracture. AB - A patient with Salmonella group D (Salmonella enteritidis) acute osteomyelitis of an operated femur is described. The patient failed to respond to chloramphenicol therapy and aztreonam therapy. The local infection that complicated the presence of a foreign body was eradicated only with the removal of the foreign body, an internal fixation plate. PMID- 3331004 TI - Treatment of pelvic fractures and associated dislocations. AB - Fractures of the pelvis result in high morbidity and mortality as a result of uncontrolled hemorrhage and associated soft tissue damage. Early reduction and fixation of these fractures has been shown to result in control of hemorrhage, decreased morbidity and mortality, and improved function. Seventeen pelvic fractures, so treated, are reported. Despite a high complication rate of almost 75%, surgical fixation resulted in rapid control of hemorrhage, restoration of hip joint congruity, early mobilization of the patient, and decreased incidence of decubitus ulcers, bronchopneumonia, thrombophlebitis, and urinary tract infection. PMID- 3331006 TI - Lord Byron's clubfoot. PMID- 3331007 TI - Aneurysmal bone cyst in early childhood. AB - A case is presented of a three-year-old child with an aneurysmal bone cyst at the right distal femoral metaphysis, a rare lesion in children in this age group. Treatment of the lesion which included thorough curettage and packing of the cyst cavity with crushed cortical bone is described. The literature is reviewed. PMID- 3331008 TI - Unicompartmental knee arthroplasty. AB - The unicompartmental knee arthroplasty is an interesting and potentially beneficial procedure that remains a controversial alternative to total knee arthroplasty and high tibial osteotomy. A critical review of the literature reveals inconsistent results using this compartmental approach to joint resurfacing. Many of the inconsistencies, however, are attributable to improper patient selection, poor component position, or inaccurate component alignment, leading to further degenerative changes and subsequent return of pain. The more recent studies, however, suggest better and more consistent results. The current indications for unicompartmental arthroplasty along with the ideal prosthetic qualifications are presented. To justify including this procedure as a sound alternative in the treatment of unicompartmental arthritis of the knee joint, however, further clinical studies are warranted. PMID- 3331009 TI - Legg-Calve-Perthes disease. AB - Legg-Calve-Perthes disease, or osteochondrosis of the femoral head, occurs predominantly in boys 4 to 7 years of age. The disease progresses through synovitis, necrosis, fragmentation, and a residual stage. Outcome can be affected by age at disease onset, the extent of femoral head involvement as determined by x-ray, and the degree to which normal range of motion is maintained. The goal of treatment is to minimize residual deformity of the femoral head and acetabulum. This is accomplished by containing the femoral head well within the acetabulum and maintaining range of motion while the disease process runs its course. In extremely young patients, containment is often achieved during normal daily living activities. Containment treatment methods include abduction casting or orthosis; surgical containment can be accomplished by femoral or innominate osteotomy. PMID- 3331010 TI - Clinical utility of insulin-like growth factor assays. AB - Insulin-like growth I and II (IGF-I and II) mediate many of the peripheral mitogenic actions of growth hormone (GH). The marked dependence of IGF levels on GH adequacy has led to the development of commercial immunoassays for IGF-I (somatomedin-C), and the widespread use of IGF-I levels in the evaluation of short stature. Proper interpretation of IGF-I levels requires consideration of assay methodology, age-related norms, clinical findings, nutritional status, and concurrent hormonal and disease processes. IGF-I levels alone cannot be used to predict stimulated GH response, but may have value in directing the clinical evaluation of a child with short stature. Low IGF-I levels may also be characteristic of a subpopulation of short children with neurosecretory GH deficiency. The role of IGF-II levels in the evaluation of short stature is uncertain, although the combination of low IGF-I and IGF-II levels is more specific for GH deficiency than either value alone. Other clinical applications for IGF assays in pediatrics are also reviewed. PMID- 3331011 TI - Growth hormone therapy in short stature. AB - Unlimited availability of growth hormone (GH), and the demonstration of increased growth velocity (GV) during GH treatment in non-GH-deficient children have suggested new indications for GH therapy in short stature. There are two principle conditions with GH-related short stature: classical growth hormone deficiency (CGHD) and growth hormone neurosecretory dysfunction (GHND). Present knowledge about the effects of GH treatment in these and other disorders of short stature are reviewed. In non-CGHD, it is not possible to predict the short-term effect on growth during GH therapy, and even if GV increases, the effect on final adult height remains to be documented. This, together with potential side effects and the high expense of GH treatment, exhort to a restricted attitude towards routine GH treatment of short children without GH deficiency. PMID- 3331013 TI - [Knowledge and practical application of colors in a dental prosthesis]. PMID- 3331012 TI - Human growth hormone therapy of non-growth hormone deficient children. AB - With biosynthetically derived human growth hormone (hGH) available in large quantities, attempts will be made to promote growth in short children who do not fulfill the 'classical' criteria for growth hormone deficiency (GHD). By these criteria, GHD is excluded if hGH levels to pharmacological stimuli exceed a definite level. Several studies have shown that a variety of short children, who are not growth hormone deficient by these criteria, will demonstrate an increased growth rate with hGH treatment. A subpopulation of children with clinical features of GHD, delayed bone age and low somatomedin levels, have low levels of spontaneously secreted growth hormone or 'bioinactive' growth hormone. These children increase their growth rates to substitution doses of hGH. In other children whose growth disorder is not likely to be caused by a disorder in the growth hormone-somatomedin axis, growth increments are occasionally seen on higher hGH doses. Future long-term studies--carefully considering the ethics of such approaches--will have to evaluate the relationships between hGH dose and both metabolic and growth responses and side effects in children with short stature in order to define more specifically further target groups of short children who will benefit from hGH therapy. PMID- 3331015 TI - [Adaptation of a reinforced resin to cavity margins in root cementum]. PMID- 3331014 TI - [Knowledge and practical application of colors in a dental prosthesis. (Continuation)]. PMID- 3331017 TI - [Calcium hydroxide and apexification]. PMID- 3331016 TI - [Effect of two mineralizing solutions on dentin]. PMID- 3331018 TI - [Some aspects of the knowledge and uses of hypnosis in dentistry]. PMID- 3331019 TI - [Hemangiomas. Literature review of this disease]. PMID- 3331020 TI - [Comparative effects of diltiazem and nifedipine combined with propranolol, in patients with chronic stable angina pectoris]. PMID- 3331021 TI - [Efficacy and tolerance of azapropazone in comparison with pirprofen in arthrosis]. PMID- 3331022 TI - [Acute leukemias]. PMID- 3331023 TI - [Retroperitoneal abscess due to perforated diverticulitis. Diagnosis and percutaneous drainage guided by ultrasonics]. PMID- 3331024 TI - [The difficult beginnings of modern surgery]. PMID- 3331025 TI - [Treatment of peptic ulcer with ranitidine and cimetidine in a single nocturnal dose]. PMID- 3331027 TI - [Short-term antihypertensive effect of the combination of furosemide and amiloride]. PMID- 3331026 TI - [Urapidil in primary arterial hypertension]. PMID- 3331028 TI - [Therapeutic use of plasma levels of drugs in clinical practice. The example of lidocaine]. PMID- 3331030 TI - [40 years of lupus: clinical and diagnostic advances]. PMID- 3331029 TI - [Risk factors in cancer of the biliary tract]. PMID- 3331031 TI - [Reception of Prof. Svante Tornvall Stromsten]. PMID- 3331032 TI - [Prevalence of problem drinkings in three internal medicine services in Santiago de Chile]. PMID- 3331033 TI - [The library in medical education]. PMID- 3331034 TI - [Amador Neghme, a leader in medical education]. PMID- 3331035 TI - Early discharge with domiciliary visits and hospital care: parents' experiences of two modes of post-partum care. PMID- 3331036 TI - [Double inlays. Nontraditional bridges]. PMID- 3331037 TI - The resin-bonded, attachment retained RPD. PMID- 3331038 TI - Common problems in teaching complete prosthodontics. PMID- 3331039 TI - Imipenem/cilastatin versus aminoglycoside plus amoxicillin plus clindamycin in the treatment of serious postoperative infections. AB - In a prospective, controlled and randomized study, the clinical and bacteriological efficacy of imipenem/cilastatin was compared to that of a standard combination of an aminoglycoside (tobramycin or netilmicin), amoxicillin and clindamycin in patients with life-threatening postoperative infections. Doses used were imipenem/cilastatin 1 g q 8 h, amoxicillin 2 g q 8 h and clindamycin 0.6 g q 6 h. Aminoglycoside doses were individual and monitored six times weekly with serum concentration assays. Thirty-eight patients were entered into the study; 19 in each group. Diagnoses were pneumonia (five in the imipenem/cilastatin group and four in the combination group), peritonitis (eight in the imipenem/cilastatin and 13 in the combination group) and septicemia (five in the imipenem/cilastatin and two in the combination group). The two groups were comparable with respect to sex, age, underlying diseases and duration of antibiotic therapy. In the imipenem/cilastatin group, 14 patients were cured and one improved (79%). In the combination group, 11 were cured and 5 improved (74%). Four patients in the imipenem/cilastatin and five in the combination group failed to respond to treatment. In the former group 77% of the bacterial isolates were eradicated and 15% were suppressed. Corresponding frequencies in the combination group were 67% and 22%, respectively. Persistence of isolated pathogens was seen in 8% and 11%, respectively. It is concluded that imipenem/cilastatin seems to be an effective and well tolerated alternative to antibiotic combinations in the treatment of life-threatening postoperative infections. It also offers the advantages of fever antibiotic doses and renunciation of aminoglycoside serum concentration monitoring. PMID- 3331040 TI - Efficacy and safety of imipenem/cilastatin in the empirical treatment of septicemia. AB - The clinical efficacy and safety of imipenem/cilastatin in the empirical treatment of adult non-immunocompromised patients with severe bacterial septicemia was studied in a prospective and open trial. The dosage of imipenem/cilastatin was 500 mg q 6 h. Of 58 patients included, 41 were evaluable for efficacy. In those patients, 35 had chronic underlying diseases and the foci of bacteremia were identified in 37; the most common ones being cardiovascular, urologic or intraabdominal infections. All isolated organisms were sensitive to imipenem with an MIC for 90% of the strains of 1 mg/l. Imipenem/cilastatin treatment resulted in rapid control of the infections in 39 of the 41 evaluable patients (95.5%). In the remaining two patients treatment had to be prematurely discontinued due to adverse effects. The causative bacterial strains were eradicated from blood in all patients who received more than one day of imipenem/cilastatin treatment but persisted sensitive to imipenem in peripheral foci in five patients (17%). Clinical and laboratory adverse reactions were noted in seven patients. In conclusion, imipenem/cilastatin was a well tolerated and effective empirical drug for treatment of septicemia. PMID- 3331041 TI - Intramuscular imipenem/cilastatin in the treatment of mild and moderate infections. AB - Imipenem/cilastatin is the combination of a broad spectrum beta-lactam antibiotic with dehydropeptidase I--an inhibitor of the metabolism of imipenem. Clinical trials have shown that imipenem/cilastatin given intravenously is effective in the treatment of mild, moderate or severe infections. A new milled form of imipenem has been developed for intramuscular use as a suspension with cilastatin, which provides a longer effective half-life of three to four hours with lower peak concentrations of imipenem. A multicenter clinical trial was instituted in the treatment of mild and moderate infections with 500 mg b.i.d. and 500 mg t.i.d. or 750 mg b.i.d., respectively. All 500 mg doses were suspended in saline while the 750 mg doses were in 1% lidocaine. A total of 346 (126 on 500 mg b.i.d., 70 on 500 mg t.i.d. and 128 on 750 mg b.i.d.) were entered. Another 22 patients received a combination of the two regimens. Of the total 346 patients entered, 286 were considered evaluable for efficacy. Skin and soft tissue infections were the most common followed by intra-abdominal, respiratory and urinary tract infections. Overall favorable outcomes were demonstrated in 98.7% with a range of 92 to 100%. All patients were included in the safety analysis. Clinical adverse experiences (AEs) were reported in 3.2% of patients with two AEs considered drug related. Both were pain at the injection site with 500 mg doses. No injection site pain was reported as AEs with the 750 mg doses. Laboratory AEs were reported in 17% and considered drug related in 7% (primarily liver enzymes changes).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331042 TI - Imipenem/cilastatin therapy for serious infections in neonates and infants. AB - Sixty-one hospitalized infants aged one day to six months were enrolled in an open, multicenter noncomparative clinical study of the efficacy and safety of imipenem/cilastatin. Patients weighing less than 1500 g (four males/ten females, Group 1) and those greater than or equal to 1500 g (31 males/16 females, Group 2) were analyzed separately. Total daily dose (divided into b.i.d. (27) or t.i.d. (34) regimens) ranged from 50 to 101.4 mg/kg given for 10.8 days (means, range 2 to 35 days) for Group 1 and 39.7 to 103 mg/kg given for 11.2 days (means, range 1 to 41 days) for Group 2. The investigators graded the intensity of signs and symptoms of infections as moderate or severe in 86 and 91% of patients in groups 1 and 2, respectively, and bacterial pathogens were isolated pretreatment in 43 and 32% of patients. Eighty-eight percent of all bacterial pathogens were susceptible to imipenem in vitro. The most commonly isolated pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. Patients who had confirmed bacterial infections and who did not receive concomitant antibiotics were considered evaluable for efficacy, including 6 (43%) in Group 1 and 15 (32%) in Group 2. Infection sites were (Group 1) respiratory (100%), and (Group 2) skin and skin structures (33%), urinary (11%), gastrointestinal (11%), septicemia alone (11%) and meningitis or respiratory (28% and 6% with sepsis, respectively). Safety analysis included all patients. Imipenem/cilastatin was well tolerated in 93% of Group 1 and 85% of Group 2 patients. Three patients' treatments were discontinued due to rash, oliguria or poor local tolerability. Three patients in Group 1 and four in Group 2 died; deaths were considered unrelated to imipenem/cilastatin. Results are as follows: (table; see text) In summary, 81% (17 of 21) of evaluable patients were clinically cured or improved, among whom 3 of 21 patients (14%) had serious clinical or laboratory adverse experiences which were considered possibly related to imipenem/cilastatin. These results are comparable to results reported with other single or multiple antibiotic regimens. PMID- 3331043 TI - Imipenem/cilastatin for pediatric infections in hospitalized patients. AB - One hundred and four children who were hospitalized for documented or suspected non-CNS bacterial infections (56 males/48 females, 22 days to 15 years old) were treated with intravenous imipenem/cilastatin for 9.4 days (range 3 to 28 days). Children up to three years of age received 100 mg/kg/day and older children 60 mg/kg/day, administered in four divided doses. Bacterial pathogens were isolated before therapy in 85%. Diagnoses in the 74 evaluable patients included bronchopneumonia with or without empyema (20%), peritonitis complicating appendicitis (16%), skin/soft tissue abscesses (14%), septicemia (11%) and miscellaneous other infections (39%). Among evaluable patients, 95% were clinically cured or improved. One patients, a marasmic child with pneumonitis due to pseudomonas, died during therapy. One evaluable patient each with shigellosis, Klebsiella pneumoniae empyema and streptococcal pneumonia had bacteriologic eradication or suppression but, due partly to noninfectious complications, had no overall clinical improvement. Most bacterial isolates (101/108) were eradicated, including many gram-negative and gram-positive aerobes and anaerobes; three pathogens persisted (one Proteus mirabilis and one Salmonella typhi, one Staphylococcus aureus); and one Escherichia coli pyelonephritis recurred after therapy ended too early. Imipenem/cilastatin was well tolerated by 91% of children. Clinical adverse experiences (AEs), none serious except for the one death, occurred in 19%; 12% were judged possibly related to imipenem/cilastatin, but none probably or definitely related. No serious laboratory AEs occurred; the most common AEs were eosinophilia (11%), urine discoloration, and infusion site pain. Imipenem/cilastatin is well tolerated and has excellent clinical efficacy in a wide variety of pediatric infections. PMID- 3331045 TI - Treatment of acute bacterial peritonitis: a trial of imipenem/cilastatin against ampicillin-metronidazole-gentamicin. AB - Imipenem/cilastatin at a dose of 0.5 g six hourly was compared to conventional combination therapy with ampicillin 0.5 g six hourly, metronidazole 0.5 g eight hourly and gentamicin 80 mg eight hourly (with dose adjustment by trough and peak serum levels) in the treatment of severe intra-abdominal infections. All antibiotics were given intravenously. Forty-five patients entered the trial. Of the 19 evaluable patients in the imipenem/cilastatin group, 16 were clinically cured with five microbiological successes and two failures. Of 24 evaluable patients in the combination group, 22 were clinically cured with one microbiological success and one failure. One patient in each group suffered an adverse effect. Patients in the I/C group tended to be older with more women and more severe infections. The origin of peritonitis was similar. I/C did not differ from combination therapy in efficacy or safety and was comparable in cost. However, I/C was easier to administer than combination therapy and there was no need for serum concentration monitoring. PMID- 3331046 TI - The dentist who painted George Washington. PMID- 3331044 TI - Imipenem/cilastatin versus amikacin plus piperacillin in the treatment of infections in neutropenic patients: a prospective, randomized multi-clinic study. AB - In this open, controlled, randomized multi-clinic trial, monotherapy with imipenem/cilastatin was compared to amikacin plus piperacillin as empiric antibacterial therapy in 210 neutropenic cancer patients. Of patients randomized, 53 (25%) had bacteriologically documented infections and of those 30 had septicemia. A further 80 patients (38%) were evaluable for clinical efficacy but did not have documented infections. Seventy-seven patients (37%) were non evaluable due to effective antibiotic treatment before the trial, early institution of other antibiotics during the trial, verified non-bacterial infections, no neutropenia or other reasons. There were no significant differences in terms of efficacy between imipenem/cilastatin and amikacin plus piperacillin but a consistent trend towards higher rates of clinical cure or improvement and of elimination of causative pathogens was noted in the imipenem/cilastatin group. In patients who were severely neutropenic (less than 0.1 x 10(9) granulocytes/l), similar cure rates were obtained in the two treatment groups--again with a tendency towards better results in the imipenem/cilastatin group. Among evaluable patients with septicemia, one patient in the imipenem/cilastatin group had persistent Staphylococcus aureus bacteremia during treatment. Five patients in the amikacin plus piperacillin group had persistent bacteremia during treatment; all but one (a Pseudomonas aeruginosa) caused by strains resistant to amikacin or piperacillin. Clinical and laboratory adverse effects were mild in the imipenem/cilastatin group although nausea was significantly more common than in the amikacin plus piperacillin group. Among patients on amikacin plus piperacillin, one died in renal failure, possibly related to treatment. Drug-related serious adverse events were reported in two additional amikacin plus piperacillin patients; one with drug fever and one with hearing loss. Microbiological adverse effects occurred in similar frequencies in the two groups. It is concluded that imipenem/cilastatin is a promising candidate for monotherapy of bacterial infections in neutropenic cancer patients. PMID- 3331048 TI - [Analysis of composite-metal after conditioning NEM alloys with electrolytic etching]. PMID- 3331047 TI - [Clinical experience with titanium implants of the "Leipzig" type with special consideration of prosthetic aspects]. PMID- 3331049 TI - Induction of ovulation with pulsatile LHRH. AB - Seven patients with primary or secondary hypogonadotropic amenorrhea and hypothalamic deficits were given LHRH intravenously by a pulsatile pump (Zyklomat Ferring). 25 treatment cycles were studied: eighteen of them were ovulatory, only one was to be interrupted because of ovarian hyperstimulation. None of the patients had any side effects caused either by the drug or by the means of delivery. The low incidence of multiple pregnancies, the tolerability and the ovulatory response make pulsatile infusion of LHRH a valid alternative to other methods for this kind of subject. PMID- 3331050 TI - Syncope and transient hypotensive states. PMID- 3331051 TI - History of cardiopulmonary resuscitation. PMID- 3331052 TI - Cardiopulmonary resuscitation: a historical review. PMID- 3331054 TI - Avian cranio-cervical systems. Part II: Arthrology of the occipito-cervical system in the mallard (Anas platyrhynchos L.). AB - The arthrology of the muscle-bone apparatus of the occipito-cervical system in the mallard (Anas platyrhynchos L.) was analysed by dissection and from histological microsections of an in toto embedded occipito-atlanto-axial apparatus. The description is primarily concerned with ligaments, membranes and fibrocartilages which were so far incompletely analysed. Several newly described elements such as the ligamentum atlantooccipitale laterale and the ligamentum ventromediale atlantoaxiale were added, as well as additional aspects such as the accurately described attachments, course and shape of most of the studied elements. PMID- 3331053 TI - Avian cranio-cervical systems. Part I: Anatomy of the cervical column in the chicken (Gallus gallus L.). AB - The osteology, arthrology and myology of the cervical column in the chicken (Gallus gallus L.) are described. The description serves as a basis for comparative and mechanical analysis of the development of stereotypic behavioural patterns. The section on osteology describes about 20 occipital elements and over 50 vertebral elements, and also informs about size differences of homologous vertebral elements. A series of suggestions concerning terminological questions refers to earlier nomenclatures. The section on arthrology comprises descriptions of intra-, capsular and extra-capsular ligaments, as well as a description of the boundaries of the work-envelope of the cervical column from an X-ray analysis. The section on myology comprises a detailed description of the occipito-cervical, ventral and dorsal subsystems of the cervical column. Special attention is given to often incompletely described muscles like the medial part of the musculus flexor colli, the musculus longus colli ventralis, the medial part of the musculus longus colli dorsalis pars caudalis. PMID- 3331055 TI - [Post-transplant renal lymphocele. Review]. PMID- 3331056 TI - [Fibroepithelial polyps of the ureter]. PMID- 3331057 TI - [Vesico-ureteral reflux and terminal renal insufficiency in childhood]. PMID- 3331059 TI - The major histocompatibility complex and protein recognition by T lymphocytes. PMID- 3331058 TI - [Carcinoma of the penis]. PMID- 3331060 TI - Use of synthetic peptides in the delineation of the role of non-antigen receptors in mast cell signalling processes. PMID- 3331061 TI - Cell anomalies associated with spaceflight conditions. PMID- 3331062 TI - The mammalian heat shock (or stress) response: a cellular defense mechanism. AB - The response of mammalian cells to abrupt changes in their local environment entails a series of coordinated transcription and translation events leading to the accumulation of a group of proteins, the stress proteins. As evidenced by the high similarities in the structure of the stress proteins amongst different organisms, the stress response appears to be a well-conserved, pre-planned strategy by which cells protect themselves against changes in their environmental circumstance. In addition to their presumed protective role, most of the stress proteins are expressed at significant levels in cells grown under normal conditions and participate in a number of biological phenomenon apparently distinct from their role during stress. For example, we have described here the role of some of the stress proteins in clathrin coated vesicle assembly/disassembly, tyrosine kinase and steroid hormone receptor function, and cell proliferation. In this regard it seems likely that we have only touched the surface regarding the many different biological processes which occur normally in cells and which involve the participation of the individual stress proteins. Of particular importance, as well, is to understand the role of the stress proteins, both individually and collectively, in protecting the cell during and after recovery from physiological stress. A breakthrough in this endeavor has come from the recent observation demonstrating the structural and biochemical similarities of many of the stress proteins and notably their ability to bind ATP. In this regard, I have described the immunological and biochemical similarities of the 70 kDa heat shock proteins with that of the 80 kDa glucose regulated protein and suggest that this family of proteins serves basically similar functions but within different intracellular compartments: the 70 kDa proteins being cytosolic and nuclear and 80 kDa being present within the endoplasmic reticulum. That a general rule is emerging here comes from the recent observation of Sorger and Pelham (in press) describing a significant sequence homology of the 90 kDa heat shock protein with that of the other glucose-regulated protein, 100 kDa. Here again, however, the proteins are distributed differently: 90 kDa is a soluble cytoplasmic protein and 100 kDa is present within the Golgi and perhaps the plasma membrane (Welch et al., 1984). Might all of the stress proteins have evolved from only a few genes with selection having resulted in different compartmentalization of the stress proteins?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331063 TI - Intermediates in class II HLA antigen biosynthesis. PMID- 3331064 TI - T-cells recognize IA conformation in the interaction with antigen presenting cells. PMID- 3331066 TI - Molecular biology of hepadnaviruses. PMID- 3331065 TI - T-cell recognition and antigen presentation of myoglobin. AB - Determination of the T-cell recognition profile of Mb by the overlapping peptide strategy revealed that the protein has six T sites. Five of these coincide with the antigenic sites while one site was recognized exclusively by T cells and not by any detectable levels of antibody. Recognition of the synthetic T sites by protein-primed T cell lines or clones indicated that T cells display an unusual peptide size requirement beyond the essential contact residues of the T site. The antigen presentation of Mb has been examined with the significant advantage of knowing the full profiles of T- and B-cell recognition of this multi-determinant antigen. Significant differences in the patterns of T-cell recognition were observed following protein-priming as compared to peptide-priming. The absence of a clear relationship between these patterns of recognition presents a strong evidence against a mechanism of antigen presentation which is dependent on the generation of peptide fragments with the latter being the 'presented' species. From this new perspective, the protein molecule must be predominantly presented in its intact form. PMID- 3331067 TI - Determinants of disease activity and evolution of chronic hepatitis type B. PMID- 3331068 TI - Serological markers of HBV infectivity. PMID- 3331069 TI - [Genotoxic activity of organic esters apt to form from 2-chlorethanol generated by the sterilization by ethylene oxide]. PMID- 3331070 TI - [Antimalarial activity of various isoquinoline alkaloids in the mouse]. PMID- 3331071 TI - Sialectasis pediatrica recurrens. PMID- 3331072 TI - [Kocher's technic for shoulder reduction: 120 years of signs of changeability]. PMID- 3331073 TI - [Primary fibrosarcoma of the bone]. PMID- 3331074 TI - [Fibrous dysplasia of bone (considerations on the review of 19 cases)]. PMID- 3331075 TI - [Juvenile bone cysts: clinico-therapeutic considerations on a review of 65 cases]. PMID- 3331076 TI - [Nosological framework of aneurysmal bone cysts. Problems of differential diagnosis and therapy. Review of 69 cases]. PMID- 3331077 TI - [Coxalgia caused by giant aneurysmal bone cyst of the wing of ilium]. PMID- 3331078 TI - [Dyschondroplasia (observations on a review of 8 cases)]. PMID- 3331079 TI - [Papineau's operation in the footsteps of the traditional surgery of chronic osteitis]. PMID- 3331080 TI - [Legg-Calve-Perthes disease (critique of treatment methods)]. PMID- 3331081 TI - [Ramazzini on occupational diseases of workers in salt mines]. PMID- 3331082 TI - The Pap smear revisited. AB - Papanicolaou smear screening for cervical cancer has become an established practice in most developed countries. This is because the cervix is relatively accessible to investigation and treatment, and early stages in the morphogenesis of cervical cancer are both recognizable and easily treated. The Pap smear is a valid test. It is simple, relatively inexpensive, reliable, and free of risk. Although the test has far from perfect sensitivity, it has high specificity, and false-positive results are rare. In most reported series, the majority of false negative results have been found to be attributable to collection errors rather than laboratory errors. Despite the importance of Pap smear screening, controlled prospective trials have not been undertaken to determine its efficiency in reducing cervical cancer incidence and mortality. However, countries with well organized programmes, wide population coverage and correct follow-up appear to have had some impact on mortality from cervical cancer. Nevertheless, coverage of high-risk groups, particularly women over 40 years of age, remains the greatest problem. Recommendations on the frequency of testing vary considerably. Statistical models indicate triennial testing may deliver almost all of the effectiveness of annual testing at a substantially reduced cost, but the numerous reports of false-negative results argue strongly in favour of annual screening. It is possible that these problems may be solved in the future by increasing the sensitivity of the test and/or by the use of additional tests. PMID- 3331083 TI - The prospective management of a coexistent hydatidiform mole and fetus. PMID- 3331084 TI - Transvaginal ultrasonographic imaging of ectopic pregnancy. PMID- 3331085 TI - Factors of activation and stabilization of DNA-methylases from Shigella sonnei 47 and Mycobacterium smegmatis butyricum cells. AB - A comparative study of factors of activation and stabilization of individual DNA methylases from two bacterial strains--Shigella sonnei 47 and Mycobacterium smegmatis butyricum--isolated by isoelectrofocusing in a pH gradient has been carried out. Storage of enzymes at +4 degrees C (pH 7.5) is accompanied by periodic changes in the methylating activity. No such changes are observed when the enzymes are stored at pI of the protein. In this case the methylases with alkaline or close to neutral values of pI remain stable over a period of at least two weeks, whereas acidic proteins are irreversibly inactivated by the end of a two-week period. A stabilizing effect of BSA on DNA-methylases of Sso 47 and Mbu strains has been demonstrated. A direct correlation between the stabilizing effect of BSA and the degree of enzyme purity has been established. Ca2+ appear to be a universal activator of methylases of the above strains; these cations produce a potent, although a short-term effect and can be used in the production of enzyme preparations with a high specific activity in DNA recombinant technology. Protease inhibitors do not exert any appreciable effect on the methylase activity upon storage. Storage at -20 degrees C and at neutral pH leads to complete inactivation of all DNA-methylases within 24 hours. In this case glycerol is fairly ineffective as a stabilizing agent. PMID- 3331086 TI - Immunospecificity and affinity studies on the monoclonal anti-gonadotropin releasing hormone (GnRH) antibodies: monoclonals produced by azotized GnRH preferentially recognise to native GnRH. AB - Monoclonal anti-GnRH(MoAb) antibodies generated by using azo-GnRH-TT conjugate were purified by affinity chromatography using azo-GnRH-BSA-Sepharose 4B column. The affinity column bound (A-MoAb) and unbound (U-MoAb) fractions were tested for immunoreactivity towards GnRH(NH2), azo-GnRH(NH2) and GnRH free acid and its fragments of sequence 4-6, 7-10 and 4-10. Both fractions reacted best with native GnRH and about 20 times less to azo-GnRH. The cross-reactivity with other GnRH(OH) fragments and affinity characteristics of A-MoAb, and U-MoAb was comparable with those of MoAb. The immunoreactivity of both the fractions was regained when C-terminus of GnRH free acid was blocked by MDP-Lys, Lys or Ala-Ala Thr-Lys-Pro-Arg-OH indicating the importance of C-terminus amide in the recognition ability of antibodies. PMID- 3331087 TI - [The Langerhans cell. Recent immunologic achievements]. AB - The epidermal Langerhans cells has been keeping, most of its secrets for about a hundred years since its first description in 1868. Its characterization in electron microscopy by Birbeck and then the use of histoenzymology (ATPase) and monoclonal antibodies (against HLA-DR, T6, LCA, C3b...) brought a new great interest on its study. The Langerhans cell must play an important immunologic role in the epidermis because of its responsibility in the antigenic information of the lymphocytes; in this way it may represent the specific epidermal differentiation of the monocyte-macrophage cell type, which are all bone-marrow derived cells. The epidermal Langerhans cell is one of the most important links in the elicitation of contact dermatitis. Recent trends about its metabolism, antigens and functions are reviewed and discussed. PMID- 3331088 TI - [Significance and evaluation of theophyllinemia in clinical medicine]. AB - The theophyllinemia variations depend upon some factors: -observance of treatment, time of blood swab posology, laboratory technic, concomitant drugs, method of adaptation selected and the mean of administration. The theophylline title is a very important biologic parameter, necessary to the asthma treatment survey through such drug. Daily posology may be adapted to this titrate. PMID- 3331089 TI - [Synthetic anticholinergics: one more for treating asthma]. AB - The author reports preliminary results and thinks that anticholinergics represent today a third drug group in asthma treatment. The anticholinergic interest in asthma treatment is double: 1. They permit a saving effect for other usual drugs in asthma; 2. They reinforce the other drugs action. PMID- 3331091 TI - [Genetic factors in asthma]. AB - Asthma is universally accepted as a multifactorial disease. So the research of constitutional risk factors must consider multiple pathways. In non atopic asthma several rare genetic etiologies are known, others are suspected but not proved. From HAMBURGER atopic allergy is a phenotype with several mechanisms. Finally some data suggest that bronchial hyper-reactivity has a genetic part. The author reviews recent knowledge and describes his personal research. His findings reveal that HLA-B 12 is significantly linked with family history of presumed atopic respiratory disease. These data are discussed. PMID- 3331092 TI - Leucocytes and the asthma process. PMID- 3331090 TI - [Extrinsic allergic alveolitis (extrinsic allergic broncho- alveolitis, pneumopathies with precipitins, hypersensitivity pneumopathies)]. AB - The author does a general survey on this subject. Having evoked the EAA history, he describes the clinical syndrome with 3 forms (sharp to chronic). He relates in a first part, the main forms linked with rural occupation, from farmer's lung disease, the most frequent, to illnesses dues to cereals, woods exposition, then the one in touch with industry as coffee workers disease, and breeders of silkworms. At last, the ones in connection with urban activities as air conditioner disease. These descriptions ended with EAA caused by a drug. Having evoked the complementary investigations necessary for diagnosis, he insists on the alveolitis washing and biochemicals studies. In conclusion, the author insists on the interest of steroids treatment in attacks. PMID- 3331093 TI - Bronchial hyper-reactivity: recent preclinical developments. AB - Airway hyper-reactivity has been recognized, if not commented upon, for many decades; however, it was the use of allergen inhalation as a clinical test that focused attention upon this aspect of asthma. In allergic asthma, an association has been drawn between inflammatory events, as manifested by the late-onset reaction to allergen, and increased reactivity of airway smooth muscle. The recognition that IgE-dependent processes determine such changes has led to extensive speculation as to pathogenic mechanism underlying the events, with the mast cell being prominent in most schemes. However, no mast cell constituent has been shown to elicit long-lasting inflammatory changes appropriate to asthma nor smooth muscle hyperplasia. Furthermore, it is now clearly evident that selective mast cell stabilising drugs do not prevent development of airway hyper-reactivity that is associated with responses to allergen. Recent pre-clinical studies have implicated platelet activating factor (PAF) as a mediator central to asthma exacerbation; with cells such as platelets, macrophages and eosinophils serving as a source of this material in IgE dependent allergic reactions. The appreciation that PAF can account for acute manifestations of airway hyper reactivity and for persisting changes of airway function (not only in acute allergic events, but also in acute and chronic non-allergic processes) may have major therapeutic implications. Established prophylactic anti-asthma drugs (i.e. cromoglycate, ketotifen, theophylline and glucocorticosteroids) inhibit such pulmonary pathology, whereas beta-adrenoceptor agonists intensify the hyper reactivity that follows exposure of pulmonary tissue to PAF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331094 TI - The relevance of house dust particles to the pathology and symptoms of asthma. AB - By measuring Antigen P1, it has become possible to define the quantities present in house dust and also both the quantities and particle size of airborne mite allergen. The results show that natural exposure is not at all like bronchial provocation and they raise real doubts over the use of bronchial provocation as a model of the way in which allergens "cause" asthma. Since it is now clear that allergens can contribute to chronic changes in the lung as well as causing acute bronchospasm, it is obvious that allergen avoidance should be a major part of the management of allergenic asthma. We believe that changing/cleaning houses can be highly beneficial to these patients and that improved methods of measuring allergens and improved methods of cleaning houses including the use of acaricides will progressively increase the role of allergen specific management of asthmatic patients. PMID- 3331095 TI - [Allergens of animal origin]. AB - Dander's Allergy still is an actual problem. In urban population the incidence increase with proliferation of domestic Animals in Houses, when, in rural population, cows and horses sensibilization frequency decrease with present evolution of farming. The newness is represented by the amelioration of knowledge in last years of biochemical nature of Antigens and the identification of major allergens. PMID- 3331096 TI - [Aspirin-induced asthma]. PMID- 3331097 TI - [Diagnosis of drug-induced allergy]. AB - Drug allergy must be in relation with a phenomenon of immunopathology which induces: Anaphylactic shock; Toxidermia; Cytopenia; Allergic Hepatitis. Diagnosis is based on the cutaneous testing and "in vitro" tests. The evidence of drug responsibility will be supplied by challenge test, practised in hospital according to special conditions. Treatment is preventive with cortisone, epinephrine, antihistamine. Treatment is also curative with those same drugs in respect to the clinical pathology. PMID- 3331099 TI - Immunological control of immunotherapy in asthma. AB - Immunotherapy of allergic diseases first called desensitization or hyposensitization is based on the introduction by parenteral administration or perhaps also by mouth of the allergens which has been considered to be responsible by the clinical symptoms. Immunotherapy partially corrects the imbalance of immune response decreasing IgE response and increasing the production of IgG1 and IgG4 antibodies either by direct effect or by an effect on specific T helpers and T suppressors subsets. PMID- 3331098 TI - [Skin tests in the exploration of perianesthetic complications]. AB - Adverse reactions in anesthesia are more and more frequent. The favoring factors are multiple but the physiopathology of these reactions are not right known: non specific histamine-release, complement activation is anaphylaxis can occur. Skin tests are an very important data for the diagnosis of these accidents. Forty patients and ten healthy subjects were tested with systematic research of a cross reactivity for curare family; myorelaxants, fluid gelatin, dextran are the tests the most frequently positive. Cross reactivity for curare family is sure and sensibilization by some medicine is possible. Then the behavior of the data is looked at; the research of the favoring factors, the non utilization of some substances and prophylactic treatment are recommended. PMID- 3331100 TI - Prevention of asthma. AB - Prevention of asthma is so important or even more important than correct treatment. Environmental measures pharmacologic prophylaxis and avoidance or prevention on offending agents, allergens, smoke, dusts, irritants and infections must be applied to each patient or each group of patients preventing the evolution of most asthmatics for an irreversible, chronic obstructive pulmonary disease. Preventive measures preceding or completing drug therapy of asthma attacks or immunotherapy are eventual for the correct management of asthmatic patients. PMID- 3331101 TI - [Effects and complications of specific immunotherapy]. AB - During the specific immunotherapy, we observe: -local reactions -systemic reactions. In most cases, it is an exacerbation of clinic symptomatology which may reach others organs nearby. Reactions will occur more or less quickly according to the kind of the extract: aqueous or delayed. Clinically, systemic reactions can induce a general trouble or an anaphylactic shock. Numerous causes could be at the beginning of these systemic reactions in relationship to an antigenic overdose or to a promoting state of health. We can observe systemic reactions at most for grass pollens or hymenoptera venoms. Standardisation of allergens is not riskless. On the opposite, it needs a best knowledge of standards which change from one laboratory to another. During specific immunotherapy of hymenoptera venom, when histamine release is positive again in more than sixty per cent we can observe correlation with systemic reactions. Epinephrine is mostly essential in treatment of anaphylactic reaction. Prevention of incidents and accidents of specific immunotherapy depends on a clinical care. This can be obtained by an expert of allergy who will be in relation with the family doctor. PMID- 3331102 TI - [Management of a patient presenting with LAV seropositivity]. AB - LAV-HTLV III serologic out-patient's supervision (clinical an immunological status), general practitioner and family medicine practitioners are able to follow up out-patients with a positive LAV-HTLV III serology. However the lack of IgM LAV-HTLV III serology is not enable to make secure our patients about the RETRO-VIRUS biological activity in their FUTURE. PMID- 3331103 TI - [Externally caused dermatitis in athletes]. PMID- 3331104 TI - [Desensitization to acarids]. PMID- 3331105 TI - [Principal mechanisms of iatrogenic pathology]. PMID- 3331106 TI - [Methods of diagnosis of contact eczema]. PMID- 3331107 TI - [Total serum IgE: normal pediatric values using the FAST IgE fluoroimmunoenzymatic technic]. AB - This reports covers the application to paediatrics of total IgE determination by the means of a new direct, sandwich type, fluorescence enzyme immuno-assay (Fluoro-allergo sorbent test:FAST IgE). The technical process is adapted for usual determinations, in case of infants and young children, of low normal rates with a good sensitivity, and of high pathological rates. IgE total usual values are established by the FAST IgE test from serums of healthy children, aged from one day to 14 years. Seven age groups are to be distinguished. PMID- 3331108 TI - [Desensitization for 4 successive years using calcium phosphate-adsorbed pollen extracts: study of sera with RAST and PRIST immunoimprints]. AB - The clinical study for four years running of desensitization treatment to adsorbed pollen calcium phosphate, prepared "at request" by Institut Pasteur, shows that these preparations produced particularly good results. The population of allergic subjects is divided into two categories as from first year of treatment: good responders and non responders. A study on the serums of these patients, in view of a different "immuno-imprint" in these two groups, has not yet been conclusive, whereas we were expecting much from this prognosis test, which would have given us better treatment information. PMID- 3331109 TI - [What problems does childhood toxocariasis currently pose? Apropos of 6 clinical cases]. AB - About six observations of toxocariasis (visceral larva migrans syndrome). We relate six observations of toxocariasis among children. In one case, an ocular localization is probable. For other five patients, they are inapparent forms. The allergologist pediatrician may be consulted because of a major hypereosinophilia (greater than 10,000/mm3) and an elevation of total IgE (greater than 2,000 UI/ml). Allergic and current parasitologic assays are negative and diagnostic key is given by toxocara serology. We insist on interest and reliability of passive hemagglutination test with a purified antigen (titer greater than or equal to 1/320). Treatment now is preferably flubendazole (50 mg/kg/day for six days) eventually renewed. PMID- 3331111 TI - [New diagnostic approaches in immuno-allergology]. AB - Methods for the diagnosis of allergy have shown considerable development in the 1980s. Older tests have been perfected (RAST) or their interpretation improved (total IgE). New tests have appeared for respiratory allergy (Phadiatop) and to follow the course of treatment (IgG RAST). Other tests are in the course of development, for example for the diagnosis of coeliac disease (gluten-specific IgA). In the future we can expect more application of specific antibody measurement and routine use of sophisticated procedures such as immunoblotting. PMID- 3331110 TI - [Are there milder forms of the syndrome called hyper-IgE? Diagnostic problems. Apropos of 2 cases]. AB - We present the observations of two boys eight and four years old whose the only clinical sign is a chronic otorrhea. We found many of usual features of the hyper IgE syndrome: raised total IgE (4000 to 8000 Ul/ml) and hypereosinophilia (1100 to 3800/mm3). We found a lowered proportion of CD8+ cells (suppressive or cytotoxic): 16 and 18% (normal values: 26 +/- 5%). The chemotaxis of polymorphonuclears is also lowered: 9.2 to 6.0 cells by microscopic field with FMLP presence (normal values 40 to 50). These two observations are compared with other literature cases where clinical picture is moderate, but biological signs very suggestive. PMID- 3331112 TI - About a peculiar disease of the cerebral cortex. By Alois Alzheimer, 1907 (Translated by L. Jarvik and H. Greenson) PMID- 3331114 TI - In memoriam Arthur Cherkin, 1913-1987. PMID- 3331113 TI - Immunological aspects of Alzheimer disease: a review. AB - Clinical and neuropathological similarities between Alzheimer disease and the transmissible spongiform encephalopathies have sparked intensive investigation of the role of nearly every arm of the immune system in the etiology and pathogenesis of Alzheimer disease. These endeavors have yielded intriguing results but no clear-cut answers. Studies of humoral and cellular immune function in patients with dementia of the Alzheimer type (DAT), immunohistochemical examinations of Alzheimer brain tissue and HLA typing of both sporadic and familial DAT are reviewed. Sporadic DAT appears to be associated with the complement allotype C4B2 in the major histocompatibility complex, which is linked very closely to HLA. Mechanisms for the role of complement in the pathogenesis of DAT are postulated. PMID- 3331116 TI - Methodological concerns: longitudinal studies of dementia. AB - Common methodological problems in longitudinal research on dementia are discussed, applying terms and constructs from the literature on normal aging. Critique of prevailing methods suggests that longitudinal studies of dementia could be improved by more extensive pilot examination of dependent measures and by more stringent control of instrumentation bias. The impact of attrition also needs to be more thoroughly evaluated before generalizations are stated about rates and patterns of decline in dementing illness. PMID- 3331115 TI - The role of the nucleus basalis of Meynert in dementia: review and reconsideration. AB - The nucleus basalis of Meynert (nbM), a cholinergic nuclear group located in the sublenticular region, receives afferent input principally from the limbic system and projects to most of the cerebral cortex. The nucleus is atrophic in dementia of the Alzheimer type (DAT) and several other dementing disorders and attempts have been made to relate cholinergic deficits as well as intellectual impairment to nbM alterations. A cortical cholinergic deficit is routinely associated with atrophy of nbM, but there is no consistent relationship between changes in nbM and histopathologic alterations of the Alzheimer type and a variable association between nbM changes and dementia. The available information suggests that atrophy of nbM and cortical cholinergic deficits have a contributory role in several dementia syndromes but cannot account for many pathologic and behavioral aspects of these disorders. PMID- 3331117 TI - Research on Alzheimer disease in German-speaking countries. PMID- 3331118 TI - The spectrum of dementia: a comparison of the clinical features of AIDS/dementia and dementia of the Alzheimer type. PMID- 3331119 TI - AIDS dementia: a review of the literature. AB - Mental disturbances associated with acquired immunodeficiency syndrome (AIDS) are related not only to profound psychosocial stress, systemic diseases, and neoplasms or opportunistic infections within the central nervous system (CNS); they are also related to the direct neurotoxicity of the etiologic human immunodeficiency virus (HIV), producing an array of both insidious and acute affective, cognitive, and behavioral dysfunction that can mimic many neuropsychiatric disorders. The precise mechanism of this direct neurotoxicity is not known, nor have the frequency, clinical course, or methods of early diagnosis been clearly established; however, a critique of 56 clinical reviews or case reports regarding approximately 800 subjects suggest that at some point following infection an HIV-induced dementia is extremely common, as are marked histopathological changes throughout the CNS. Treatment strategies are discussed. PMID- 3331120 TI - Biosynthesis of the C-terminal amide in peptide hormones. AB - Recent developments in the study of peptide amidation are reviewed. The main areas covered are assay procedures, purification of amidating enzymes, co-factors and regulation, mechanism and specificity of the amidating reaction, and multiple forms of the amidating enzyme and glycosylation. Discussion is presented on aspects that are poorly understood and new areas open to investigation are indicated. PMID- 3331121 TI - Suppressors suaC109 and suaA101 of Aspergillus nidulans alter the ribosomal phenotype in vitro. AB - A new homologous, cell-free system for protein synthesis has been devised for use with ribosomes and elongation factors from Aspergillus nidulans. Ribosome preparations from strains with either the suaA101 or suaC109 mutations have a higher misreading ratio (non-cognate:cognate amino acid incorporation) in the presence of hygromycin than controls. They can be classed as fidelity mutants. These results also prove that the mutations must be in genes coding for ribosomal proteins or enzymes which modify ribosomal proteins post-translationally. Alternatively, the genes could code for translation factors. PMID- 3331122 TI - Expression in Escherichia coli of active human alcohol dehydrogenase lacking N terminal acetylation. AB - Human alcohol dehydrogenase (ADH, beta beta isozyme of class I) was expressed in Escherichia coli, purified to homogeneity, and characterized regarding N-terminal processing. The expression system was obtained by ligation of a cDNA fragment corresponding to the beta-subunit of human liver alcohol dehydrogenase into the vector pKK 223-3 containing the tac promoter. The enzyme, detected by Western blot analysis and ethanol oxidizing activity, constituted up to 3% of the total amount of protein. Recombinant ADH was separated from E. coli ADH by ion-exchange chromatography and the isolated enzyme was essentially pure as judged by SDS polyacrylamide gel electrophoresis and sequence analysis. The N-terminal sequence was identical to that of the authentic beta-subunit except that the N-terminus was non-acetylated, indicating a correct removal of the initiator methionine, but lack of further processing. PMID- 3331123 TI - Facts and fallacies involved in the epidemiology of isocyanate asthma. AB - Personal experience and analysis of the medical literature on isocyanate asthma shows, that the reported incidence of this disease varies between 0 and 25%. Reasons for differences in observed incidence are intensity of isocyanate exposure, criteria for diagnosis, mode of calculation, sensitizing capacity of different isocyanates, individual predisposition and confounding factors (adjuvants). There is no geographical or ethnical prevalence. Work places at risk are those with isocyanate concentrations above 20 ppb (ceiling). PMID- 3331124 TI - Prognosis of occupational asthma induced by isocyanates. AB - Several studies on the prognosis of isocyanate-induced asthma show that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work, and that further exposure to isocyanates in sensitized subjects leads almost invariably to persistence of respiratory symptoms and of bronchial hyperresponsiveness and the deterioration of airway function. Specific bronchial reactivity to isocyanates may change after cessation of work; however, some subjects continue to be sensitive to TDI several months after cessation of work. The determinants of an unfavourable prognosis for asthma seem to be the same as those for other types of occupational asthma due to low molecular weight compounds (i.e. red cedar asthma): long duration of exposure before the onset of asthma, long duration of symptoms before diagnosis, airway obstruction, and dual airway response after specific challenge tests. Also, single acute exposure to high levels of TDI in the workplace (spills) can result in persistent nonspecific bronchial hyperresponsiveness. Potential mechanisms of persistence of symptoms and of nonspecific bronchial hyperresponsiveness may be chronic inflammation, bronchial smooth muscle alteration, autonomic nervous system disregulation. PMID- 3331125 TI - Why did density dependence of maximal expiratory flows not become a useful epidemiological tool? PMID- 3331127 TI - [Reasoning models viewed within the framework of medical expert systems]. PMID- 3331126 TI - The use of maximum expiratory flow-volume curves on air and He/O2 to assess peripheral pressure losses in the airways. PMID- 3331128 TI - [The leprosy bacillus: expectations for culturing and vaccination]. PMID- 3331129 TI - [Bacteria and plasmids. A special mechanism for adaptation to the environment: the use of parasites]. PMID- 3331130 TI - Review of clinical experience with microbial keratitis associated with contact lenses. PMID- 3331131 TI - Endothelial blebs in clear corneal grafts fitted with soft contact lenses. PMID- 3331132 TI - Changes in plant gene expression during stress. AB - Changes in gene expression which occur during periods of environmentally induced stress provide models for the study of gene regulation. Several types of stress have been shown to elicit a specific and reproducible pattern of gene expression in various plant species. These stress factors include heat shock, anaerobiosis, plant pathogens, oxygen free radicals, heavy metals, water stress, and chilling. In some cases, changes in specific genes have been identified, such as increases in the expression of the gene encoding the phytoalexin-synthesizing enzyme in pathogen elicitor-treated cells. However, in most cases, the functional identity of stress-induced genes is unknown. The alterations in gene expression during stress usually are rapid and repeatable, making these genetic systems ideal for examination of factors and mechanisms involved in gene regulation. PMID- 3331133 TI - [The development and status of maxillofacial prostheses in Yugoslavia]. PMID- 3331134 TI - Ticks (Acari:Ixodidae) of the Blue and White Nile ecosystems in the Sudan with particular reference to the Rhipicephalus sanguineus group. AB - Twenty-four adult ixodid tick species, infesting livestock and some wildlife hosts along the Blue and White Nile in the Sudan, were identified. Three species, Boophilus geigyi, Rhipicephalus camicasi and R. bergeoni, were recorded for the first time from the Sudan. Tick numbers on indigenous breeds of cattle (Bos indicus) were relatively low, ranging between 17.1 and 40.5 per animal. Young cattle grazing with the herd carried significantly fewer ticks than older animals. With the exception of B. annulatus and R. simus, which have extended their distribution further north into Blue Nile, Gezira and Khartoum Provinces, the distribution patterns of the most important cattle ticks have been relatively unchanged over the past 30 years. The Rhicicephalus sanguineus group was represented by six species. R. camicasi was the only species present on cattle, sheep and goats in the north in Kassala and Khartoum Provinces, whereas this species occurred sympatrically with R. guilhoni and R. turanicus further south in Gezira and Blue Nile Provinces. In the Southern Region of the Sudan only R. turanicus and R. guilhoni were present, the latter being by far the predominant species, with peak activity towards the end of the rains in the Jonglei Canal Area. R. bergeoni was collected once, from cattle near the Ethiopian border in Blue Nile Province, whereas R. sanguineus sensu stricto was collected throughout the study area, from domestic dogs only. Finally, R. sulcatus was found once on a hare. The distributions of the common tick species are correlated with the occurrence of tick-borne diseases of domestic animals and recommendations for the control of tick-borne diseases and their vectors in the Sudan are given. PMID- 3331135 TI - [List of members of the Medical Society of French-Speaking Black Africa as of 1 January 1986]. PMID- 3331136 TI - [Neurological expressions of systemic lupus erythematosus]. PMID- 3331137 TI - [DNA identification in the diagnosis of infectious diseases-- status in the present and near future]. PMID- 3331138 TI - [War images in the medical press]. PMID- 3331139 TI - [Amiodarone management of life-threatening ventricular arrhythmias]. PMID- 3331140 TI - [Risks and benefits of hormonal contraception]. PMID- 3331141 TI - [Metabolic effects of contraceptive pills]. PMID- 3331142 TI - [Subcutaneous hormone capsules]. PMID- 3331143 TI - [Contraceptive coils and their problems]. PMID- 3331144 TI - [Contraceptive methods]. PMID- 3331145 TI - [Female sterilization]. PMID- 3331146 TI - [Postcoital contraception]. PMID- 3331148 TI - [Prognosis of ovulation based on contraceptive methods]. PMID- 3331149 TI - [Prevention of teenage pregnancy]. PMID- 3331150 TI - [Pregnancy interruption and childbirth after contraception]. PMID- 3331147 TI - [Hormonal coils]. PMID- 3331152 TI - [Hormonal contraception and other drug treatments]. PMID- 3331151 TI - [Chronic illness and contraception]. PMID- 3331153 TI - [The psychology of contraception]. PMID- 3331154 TI - [Natural antitumor compounds of vegetable origin]. AB - This review deals with various aspects of biochemical cancer chemotherapy based on vegetable products. Nearly all isolated vegetable agents know to have in vitro or in vivo anticancer or immunostimulation activity are collected. These researches aim to develop selective antitumor agents. PMID- 3331155 TI - [Novel characteristic of the genus Campylobacter: Campylobacter-like organisms]. AB - The first report of human infections due to Campylobacter dates back to 1947. These microorganisms, classified initially as Vibrio, had been known for many years as agents of several diseases in animals. In 1963 they were grouped in the new Genus Campylobacter belonging to Spirillaceae. Campylobacter are ever more important, particularly C. jejuni, which is an ubiquitous agent of diarrhoea in children. Other microorganisms of this Genus, the "gastric Campylobacter-like organisms" type I, otherwise known as Campylobacter pyloridis, are responsible for gastric diseases. PMID- 3331156 TI - [In vitro activity of imipenem (N-formimidoylthienamycin), a new carbapenem antibiotic]. AB - Imipenem is a beta-lactam carbapenem antibiotic, N-formimidoyl thienamycin derivate. Imipenem is highly active against gram-negative aerobes and also highly active against gram-positive aerobes and virtually all anaerobes, with MICs very low and MBCs equal or only two-four dilution higher, it has a low degree of affinity for all types of beta-lactamases, shown a good post-antibiotic effect, it is a potent inhibitor to peptidoglycan with a greatest affinity for PBP2 and PBP1, in gram-negative bacteria, and for PBP3, PBP1 and PBP4, in gram-positive bacteria. The precocious bactericidal activity belongs to its low molecular weight, the characteristic of zwitterionic compound, to its hydrophobicity and to, in finally, its compact molecular structure. PMID- 3331157 TI - [Infectious complications of continuous ambulatory peritoneal dialysis]. AB - Continuous ambulatory peritoneal dialysis (CAPD) is of proven value in the treatment of many patients with chronic renal failure. Infective peritonitis remains the major complication of this form of therapy and repeated infections may result in catheter removal and conversion to haemodialysis. The most appropriate antibiotic treatment, the duration and route of administration are still areas of investigation. The aim of this paper is to discuss the diagnosis, management and prevention of peritonitis in CAPD. PMID- 3331158 TI - [Current problems in the laboratory diagnosis of roseola]. PMID- 3331160 TI - [Retroviruses: current classification system]. AB - Based on the various viral properties, the recent Retrovirus classifications are reported. After describing the HIV characteristics with the transactivation capability, the authors include the HIV among the Lentivirinae. PMID- 3331159 TI - [Determination of the bactericidal potency of cefatrizine and other oral antibiotics against Haemophilus influenzae, Klebsiella pneumoniae and Streptococcus pyogenes]. AB - The in vitro determination of the T log and the minimal bactericidal time of cefatrizine was evaluated against H. influenzae, Str. pyogenes A isolated from clinical specimens. and K. pneumonia ATCC 10031 and compared with that of amoxycillin, cefaclor, cefroxadine and miocamycin against the same bacterial strains. Cefatrizine demonstrate the shorter TMB against all bacterial strains and antibiotic tested with MBCs. PMID- 3331162 TI - [Videodensitometric assessment of right and left ventricular functions by digital subtraction angiography]. AB - Right and left ventricular volumes and systolic indices were determined by intravenous digital subtraction ventriculography in 50 patients with various heart diseases. Using a constant injection speed of 35 ml Renografin-76 contrast medium, serial right and left ventriculograms were obtained in the 30 degree right anterior oblique projection. Right ventriculograms were also obtained in the 60 degree left anterior oblique projection. The videotape recordings of subtracted images were continuously digitized into 128 X 128 eight bit (256 gray scales) pixel matrices using an image-processing computer. The endocardial outlines of the right and left ventricles were drawn manually using a joystick, frame by frame, for each cardiac cycle. By integrating overall the pixel densitometric counts within this outline for each frame, the computer generated a time-density curve with maxima and minima represented in the end-diastolic and end-systolic frames, respectively. Systolic indices including ejection fraction (EF), one-third ejection fraction (1/3 EF) and the peak ejection rate (PER) were derived from the time-density curve. Right ventricular volume was determined by the single-plane or biplane mathematical formulae of Ferlinz et al., and left ventricular volume was calculated by the area-length method in the 30 degree right anterior oblique projection. Results by the two geometric methods correlated well for right ventricular volume (r = 0.84) and for EF (r = 0.80). Right ventricular densitometric counts correlated closely with single-plane volume (r = 0.91). Right ventricular ejection fraction (RVEF) determined by videodensitometry also correlated satisfactorily with that by single-plane angiography (r = 0.74).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331161 TI - 125I-insulin degradation by normal rabbit erythrocyte membranes solubilized in different detergents. PMID- 3331163 TI - [Diagnosis of acute ischemic heart disease using a personal computer]. PMID- 3331164 TI - [Surface cell markers in lymphatic leukemia and lymphoma]. PMID- 3331166 TI - [Fear of the father]. PMID- 3331165 TI - [Adolescence and solitude]. PMID- 3331168 TI - 5-Bromodeoxyuridine in vivo labelling of M13 DNA, and its use as a non radioactive probe for hybridization experiments. AB - We describe the in vivo production of 5-bromodeoxyuridine- (5-BUdR) labelled M13 DNA by a thymine-requiring Escherichia coli strain. We show that the 5-BUdR labelled M13 single-stranded DNA is not extruded into the culture medium, but accumulates inside the bacterial cells. On the basis of this observation, a procedure involving FPLC gel filtration already reported and used for the isolation of plasmid DNA has been adapted for the isolation of at least 90% pure 5-BUdR-labelled single-stranded DNA. An M13 probe, containing part of the Hepatitis B Virus (HBV) genome was constructed, and the corresponding 5-BUdR labelled single-stranded DNA was used in hybridization experiments to detect homologous HBV target DNA. Picogram amounts (10(-19) moles) of the probe itself or the target DNA could be detected, by monoclonal anti-5-BUdR antibodies in an immunoenzymatic assay. PMID- 3331167 TI - Surfactant protein of molecular weight 28,000-36,000 in cultured human fetal lung: cellular localization and effect of dexamethasone. AB - We have examined the effect of explant culture and hormones on the major surfactant associated protein of Mr 28,000-36,000 (SP 28-36) in human fetal lung. Explants of 16- to 23-week gestation lung were maintained for up to 5 days in culture. Polyclonal antibodies raised to SP 28-36 purified from alveolar proteinosis lung lavage were used in immunofluorescence experiments (n = 11). There was no specific fluorescence seen in frozen sections of preculture tissue. In explants cultured without serum or hormones, fluorescence was seen in most epithelial cells lining potential airspaces. In cultures treated with 10 nM dexamethasone and 2 nM T3 much brighter fluorescence was seen in virtually all epithelial cells. Immunofluorescence studies on cell monolayers prepared from explants confirmed that SP 28-36 is found in the cytoplasm of type II cells but not in fibroblasts. The pattern of fluorescence was consistent with the presence of SP 28-36 on rough endoplasmic reticulum. SP 28-36 mRNA was measured in isolated cell populations using a 32P-labeled cDNA probe. mRNA levels were manyfold higher in type II cell preparations (purity 78-92%) than in fibroblasts (purity 81-97%). A competitive enzyme linked assay was developed to quantify SP 28-36. The SP 28-36 content of five lungs before culture (17-23 weeks) was less than 0.02 microgram/mg DNA. During explant culture without hormones the SP 28-36 content increased exponentially. Exposure to dexamethasone accelerated the increase in SP 28-36 content. T3, alone or in the presence of dexamethasone, did not influence SP 28-36 content. We conclude that SP 28-36 content is very low in human fetal lung before 24 weeks gestation. Explant culture and treatment with dexamethasone synchronize development of type II cells from epithelial precursors, and induce synthesis of SP 28-36 in type II cells. These findings provide evidence of concomitant regulation by glucocorticoids of the phospholipid synthetic enzymes and the major protein of pulmonary surfactant. PMID- 3331169 TI - Molecular diagnosis of infectious diseases by nucleic acid hybridization. AB - Diagnostic microbiology has traditionally relied on the cultivation of an infecting agent in an in vitro system. However, the limitations of these methods have led to the development of alternative, molecular techniques which can detect specific microbial proteins or nucleic acids directly in body fluids. One such method, nucleic acid hybridization, has many attractive features including the potential for high sensitivity and specificity, the detection of a chemically stable analyte and the use of uniform reagents. Nucleic acid hybridization reactions have been used to detect a variety of microbial pathogens in assay formats using extracted nucleic acids or tissue sections. However, wider application of these techniques is limited by the fact that current methods employ radioisotopically labelled probes and cumbersome assay procedures. Solutions to these problems have been sought by the development of non radioactive hybridization techniques which utilize enzymatic detection methods and by the development of rapid hybridization assays performed in solution. Further improvements in labelling techniques, assay formats and enzymatic detection methods should allow for the wider application of nucleic acid hybridization reactions in diagnostic microbiology. PMID- 3331170 TI - Human monoclonal antibodies as cellular and molecular probes: a review. PMID- 3331171 TI - A novel tumour marker related to the c-myc oncogene product. AB - We have studied the utility of the c-myc oncogene product as tumour marker using a set of monoclonal antibodies raised against synthetic peptides constructed from sequence data of the human c-myc oncoprotein. One antibody, Myc1-9E10, raised against the C-terminal 32 amino acids, has been shown to detect specifically the 62 kDa c-myc gene product in tumour cells. Immunoblotting of sera and urine with this antibody consistently revealed a single 40 kDa band (p40). Quantitative analysis using dilution dot immunoblotting demonstrated a considerable increase in the titre of p40 in the sera of 51 patients with a wide range of advanced solid tumours when compared with 17 healthy controls and 50 patients with non malignant diseases. Serial measurement of the p40 titre in 12 patients with resected colorectal carcinoma shows a gradual return to normal with a half-life of 7 days. Our data suggests that p40 may be a useful new marker for monitoring tumour activity. PMID- 3331172 TI - Flow cytometric quantitation of the c-myc oncoprotein in archival neoplastic biopsies of the colon. AB - The c-myc oncogene encoded protein product, p62c-myc, was assayed simultaneously with DNA in populations of individual nuclei extracted from archival biopsies of colonic neoplasia. Both the protein and DNA were assayed fluorimetrically using flow cytometry with a synthetic peptide induced monoclonal antibody (MYC 1-6E10) for the protein and propidium iodide for DNA. The nuclear p62c-myc levels increased progressively from normal mucosa through polyps to carcinomas. However, there was a trend for the more poorly differentiated carcinomas to exhibit lower levels than moderately and well-differentiated tumours, p = 0.085. These results agree with those published previously with the same antibody using Western blotting for protein extracted from fresh frozen tissue and immunocytochemical assessment. Furthermore, flow cytometry is able to effect discriminations between subsets in heterogeneous populations using DNA as a second parameter which Western blot bulk studies cannot. PMID- 3331173 TI - Sensitive detection of genes by sandwich hybridization and time-resolved fluorometry. AB - Europium has been used as a non-radioactive marker in immunoassays as this metal can be detected with high sensitivity by time-resolved fluorometry. In this work streptavidin labeled with europium was used to detect biotinylated probes in a sandwich nucleic-acid hybridization assay with microtitration strips as the solid phase. pBR 322 plasmids were detected with a sensitivity of 4 x 10(5) molecules. As the sample is added in solution in sandwich hybridization, fast and simple sample pre-treatment can be used without encountering background problems. The method was applied to test bacterial samples of uropathogenic Escherichia coli strains for the presence of the beta-lactamase gene. PMID- 3331174 TI - Flexor tendon injuries. Part 1. Anatomy, physiology, biomechanics, healing, and adhesion formation around a repaired tendon. AB - A review of the advances that have been made in recent years toward a better understanding of flexor tendon anatomy, physiology, biomechanics, healing and the development of adhesions around a repaired tendon. Despite the advances that have been made, results of flexor tendon repairs, particularly in the area of Zone 2, have been less than satisfactory. Adhesions also seem to be a biologic inevitability. A need for continued investigation. PMID- 3331175 TI - Flexor tendon injuries. Part 2. Flexor tendon repair. AB - The principles of atraumatic flexor tendon repair are reviewed. It is noted that tendon repair of the profundus and superficialis tendons-primary or delayed primary-should be carried out in all zones of flexor tendon interruption. Whenever possible, repair of the flexor tendon sheath also seems appropriate. A supervised program of early motion may prove beneficial, though restoration of function to a digit may be long and tedious, thus requiring a high degree of patient motivation and participation. PMID- 3331176 TI - Thermographic assessment of bone and joint disease. AB - Thermography, a noninvasive technique with no known toxicity, represents a useful addition to our diagnostic armamentarium. It has documented efficacy in specific diagnostic circumstances and possible motivational applications. Its eventual position in our general diagnostic armamentarium will be dependent upon additional, well-designed clinical-pathologic correlation studies, the bases of which are presented herein. PMID- 3331177 TI - Human bites to the hand. AB - Because of the virulence of human oral flora, complications from relatively common human bites can be far more serious than those caused by animal bites. Types of infection of various kinds of human bites, the common pathways of extension of these infections and the appropriate treatment for these injuries as well as the prevention of what may be devastating and crippling sequelae are reviewed. PMID- 3331178 TI - Acute perilunate dislocations. AB - In reviewing the literature on acute perilunate dislocations, we found wide disagreement as to the best treatment for these injuries. A fundamental background on the evolution and evaluation of the perilunate dislocation is given, in which the older literature was found to support initial closed treatment. Subsequent follow-up has proved that open treatment may actually give similar, yet more predictable, results. It is concluded that in most patients- and especially in a noncompliant city hospital population--open reduction internal fixation will achieve the best overall results in the treatment of these injuries. PMID- 3331179 TI - Computer corner #13. Computerized examinations in orthopaedics. AB - Computerized examinations can play an important role in the evaluation and education of trainees in orthopaedics. Several centers in the United States and Canada are currently using these, thus allowing an exchange of examination questions. Once a system is set up, only minimal involvement on the part of the instructor and office staff is required. All participants--trainees and instructors--can benefit from computerized examinations. PMID- 3331181 TI - The properties of skeletal muscle. AB - The authors review the musculoskeletal system and the controversy that surrounds methods for improving and strengthening it. Disorders brought on by over utilization, deficient working habits, lack of appropriate maintenance care and intercurrent stress and fatigue from repetitious daily tasks and poor sleeping habits are recognized and discussed. Also discussed are muscle structure and its relation to the contractive state, muscle energy requirements, motor control, source of muscle strength and factors modulating it, training adaptations in skeletal muscle, methods of strength training, erogenic aids including anabolic steroids and electrical stimulation and the pathologic states in muscles. PMID- 3331180 TI - Chronic rotator cuff tears. AB - The treatment of chronic rotator cuff tears is a controversial topic. Proponents of conservative therapy cite cadaver studies and postulate that with time the inflammatory reaction will subside and that although the structural integrity of the cuff may not be completely intact, the patient will nevertheless have an excellent functional result. On the other hand, operative intervention proponents contend that better mechanical advantage to shoulder motion will be present with an intact rotator cuff and that excision of necrotic tissue will alleviate impingement and pain. This paper is an overview of the topic and discusses some of the treatment modalities. PMID- 3331182 TI - Flexor tendon injuries. Part 3. Free tendon grafts. AB - Tendon grafting, to restore digital flexion, is the treatment of choice in those cases in which the flexor tendons, divided in Zone 1 or Zone 2 cannot be directly repaired. The indications and techniques for conventional free tendon grafting are presented and discussed. Particular surgical procedures for use in cases with interruption of profundus and superficialis and in cases with an intact flexor digitorum superficialis are described. PMID- 3331183 TI - Slipped capital femoral epiphysis, unsolved adolescent hip disorder. AB - Slipped capital femoral epiphysis remains the unsolved adolescent hip disorder. The epidemiology, clinical signs and symptoms, pathology, and radiographic findings have been well described and are reviewed. However, since we do not know the cause of the disorder, prevention is not possible and an ideal method of treatment has not yet been found. Goals of treatment, methods of treatment, as well as results and complications of treatment are discussed. PMID- 3331184 TI - Congenital arteriovenous malformation of the hand. AB - A congenital arteriovenous malformation of the hand occurred in a 39-year-old woman. Review of the literature reveals that this presents a challenging therapeutic problem. A case report is presented, along with a review of the laboratory assessment and treatment options. PMID- 3331185 TI - Complications of wire mesh in acetabular reconstruction. AB - Stainless steel wire mesh has been used for many years to reinforce acetabular cement. A case has been seen in which considerable corrosion and disintegration of the mesh were noted, with gross metallosis of the surrounding tissues. It is postulated that galvanic corrosion occurred between the stainless steel mesh and the cobalt chrome femoral prosthesis. PMID- 3331187 TI - Microsurgery reconstruction of lower extremity injury. PMID- 3331186 TI - Arthroscopy update #2. Arthroscopic removal of femoral intramedullary rod. AB - A 51-year-old man with a femoral shaft fracture previously treated by open intramedullary rod fixation developed a symptomatic distal migration of the rod. A technique for arthroscopic removal of the femoral rod is described. This report highlights the expanding role of arthroscopy in the treatment of orthopaedic disorders. PMID- 3331189 TI - Flexor tendon injuries. Part 4. Staged flexor tendon reconstruction and restoration of the flexor pulley. AB - Staged reconstruction of the flexor tendon is discussed and several surgical techniques involving implantation of a silicone or silicone-Dacron-reinforced gliding prosthesis into a scarred flexor tendon bed are described. Flexor pulley restoration and the importance of maintaining strong pulley support are discussed and surgical techniques including those for flexor tendon grafting and reconstruction are described. Though the results of these procedures leave much to be desired, the proper technique utilized under the right circumstances can restore satisfactory function following interruption or destruction of flexor tendons. PMID- 3331188 TI - Hip flexion deformity secondary to acute pyogenic psoas abscess. AB - The data from ten patients who underwent incision and drainage of an acute pyogenic abscess were studied with respect to the presence of an associated hip flexion deformity prior to incision and drainage of the abscess, bacteria cultured intraoperatively, treatment of any persistent hip flexion deformity postoperatively, and any additional sequelae noted at an average follow-up of seven years (range, one to 17 years). Six of the ten patients presented with an associated hip flexion deformity. In three patients, the deformity had resolved spontaneously and completely--in one by the third postoperative day and in two by the 45th postoperative day. Follow-up of these patients at up to 17 years revealed no residual flexion deformity. The flexion deformity in two of the six patients improved following incision and drainage, but residual flexion deformities of 10 degrees and 15 degrees were noted at three- and six-year follow up, respectively. The sixth patient was treated with skin traction both preoperatively and postoperatively, but it was ineffective in totally correcting the deformity. Follow-up of this patient at one year revealed a residual 15 degrees hip flexion deformity. All six patients had normal ambulation at follow up examination. Bacteria cultured intraoperatively did not appear to affect either the initial development of the flexion deformity or the time to resolution following incision and drainage of the abscess. Of 183 patients with an acute pyogenic psoas abscess reviewed in 14 series from the literature, 96% (176/183) presented with an associated hip flexion deformity. A hip flexion deformity in a patient with fever and pain on attempted extension of the thigh is therefore a reliable sign for the diagnosis of an acute pyogenic psoas abscess. Treatment may be indicated for a persistent deformity following incision and drainage. Skin traction is the most commonly used and successful method of treatment. Persistence of the hip flexion deformity postoperatively may be secondary to fibrosis within the psoas sheath or actual substance of the muscle, or both. A mild residual flexion deformity may be present years after incision and drainage but apparently will cause no functional abnormality. PMID- 3331190 TI - Flexor tendon injuries. Part 5. Flexor tenolysis, rehabilitation and results. AB - In this five-part series, we have attempted to review our current understanding of flexor tendon anatomy, physiology, biomechanics, healing and adhesion formation around a repaired tendon. The methods of acute flexor tendon repair, conventional free tendon grafting, staged flexor tendon reconstruction and pulley restoration have been discussed as well as flexor tenolysis, rehabilitation and results. From these articles it may be seen that flexor tendon surgery is a complex and difficult art which requires a thorough appreciation of the normal flexor tendon system, the exact status of that system following injury and a strong understanding of the techniques which may be best utilized to restore flexor tendon function. The procedures described require both technical skill and experience and postoperative therapy programs must be carefully instituted based on the unique status of each patient. With the important advances occurring in many areas of flexor tendon surgery, it is realistic to believe that in the near future the techniques described in these articles may be substantially altered and modified. Results will continue to improve until the patient and surgeon can realistically expect to return most digits to nearly full function after flexor tendon interruption. PMID- 3331191 TI - New concepts in bone grafting. AB - The authors review the diagnostic and surgical imaging aspects of a number of recent bone grafting procedures in the orthopaedic management of various osseous and articular disorders. They discuss several innovative new approaches to bone grafting as well as the use of a variety of bone grafting substitute materials. They discuss the three types of bone graft available for orthopaedic reconstruction; autograft, allograft or homograft and xenograft or heterograft. They stress that an awareness of the radiographic features of each of the various bone grafting techniques is important to the physician dealing with musculoskeletal disorders in determining the results of his efforts. PMID- 3331193 TI - Dupuytren's contracture: wound irrigation to prevent hematoma. AB - Hematoma is one of many complications that can follow surgery for Dupuytren's contracture. In this article, along with a discussion of previously used methods, a technique developed to prevent postoperative palmar hematoma is reviewed. The technique consists of inserting a polyethylene tube into the surgical wound prior to closure and then irrigating the wound with cold Ringer's solution at the rate of approximately 75 cc/hr for 24-36 hours postoperatively. The review involved 101 patients with 124 procedures, 76 of which were performed using the new technique. The incidence of hematoma in the patients without irrigation was 6.3%, while that in the patients with irrigation was 0.0%. No deleterious side effects of this technique were detected. PMID- 3331192 TI - Desmoid tumors in childhood. AB - Eight cases of extraabdominal desmoid tumors in children are reviewed. Seven were located in the pelvis or forearm, and the most common presenting complaint was a slowly enlarging mass. In all cases, diagnosis was established by open biopsy, and initial treatment was by surgical excision. At follow-up (average, 5.8 years), six patients were tumor free. Desmoids are benign tumors that usually carry a good prognosis. There is no difference between the tumor behavior in children and adults. The treatment of choice is wide local excision. If vital structures are involved, it may be more appropriate to preserve function by performing partial tumor excision. For quiescent recurrent tumors, observation is appropriate management, but if further treatment is required, reexcision or radiotherapy may be tried. PMID- 3331194 TI - Unstable intertrochanteric fractures of the hip. AB - In spite of a host of operative techniques and fixation devices, no one method of treatment has gained universal acceptance for the treatment of unstable intertrochanteric hip fractures. Although it is important to determine if a fracture is stable or unstable, stability should be considered a relative term. Degree of stability should be assessed by a careful review of the preoperative radiographs as well as postreduction films and palpation of comminution at surgery. Those fractures with minimal to moderate posteromedial comminution are probably best managed by anatomic reduction and compression hip screw fixation. The collapsing device will allow the fracture to obtain its own stability (Figure 5). However, in severely comminuted fractures the screw may slide completely prior to the stable apposition of cortical surfaces of the proximal and distal fragments. Fixation failure will result in a significant percentage of these fractures unless a stable reduction is obtained surgically. Medial displacement osteotomy, valgus osteotomy, or augmentation with cement should be considered in these high-risk fractures. Regardless of the reduction technique the proximal fragment must be aligned properly with the femoral shaft. If the major fracture fragments are prevented from reaching a stable configuration, fixation failure will likely occur (Figure 6). PMID- 3331195 TI - Extremity tissue expansion. AB - The gradual mechanical distention of tissues in the extremities using inflatable balloons allows elimination of local defects or expansion of known extremity donor sites to facilitate other reconstructive requirements. Complication rate are higher for extremity tissue expansion, and proper caution must be adopted if this concept is to be valuable for applications in the extremities. PMID- 3331196 TI - Melorheostosis: two case presentations and review of the literature. AB - Two cases are presented. Case #1, a 27-year-old Caucasian male presented with chronic right leg pain. Case 2 was a 23-year-old Caucasian female with right fifth finger pain. The clinical examination was benign except for mild tenderness of many years duration. No deformities were present in the male patient, the female patient did exhibit mild clinodactyly. The pain was described as constant, low grade, and dull. Plain roentgenograms of both patients demonstrated a hyperostotic process typical of melorheostosis and the bone scans demonstrated increased bone activity. A CAT scan demonstrated both endosteal and periosteal hyperostosis in our male patient. The biopsies of both patients were consistent with the clinical diagnosis of melorheostosis. A discussion and review of the literature covering this process is presented. PMID- 3331198 TI - Rehabilitation management of the rheumatoid foot. PMID- 3331197 TI - Eikenella corrodens infection of the hand--a case report and literature review. AB - Eikenella corrodens, a gram-negative, slow-growing rod, belongs to the normal flora of mucous membranes. Infections of the hand including this pathogen, are described in human bite and clenched fist injuries. Our case demonstrates another possibility of wound contamination with normal oral flora causing Eikenella corrodens infection. The consequences due to the delay of appropriate therapy are discussed. PMID- 3331199 TI - Ultrasound-guided fine needle aspiration biopsy of the liver. AB - Our experience with ultrasound-guided fine needle aspiration biopsy in 65 patients suspected of having malignancy of the liver is reviewed. The results of cytology smears were correlated with cell block sections, histology of the liver and/or other relevant sites, and clinical course. Aspiration cytology was positive in 52 of 57 patients (91%) who had a final diagnosis of malignancy, and there were no false positive results. The cell type reported by cytology correlated completely in 23 of 27 cases with histological confirmation, whilst cytology showed better differentiating features in the remaining 4 cases. The microscopic appearances have been described. There was only one significant complication of the procedure. PMID- 3331200 TI - An essay on friendships of utility: resolving the disalignment between nursing education and nursing service. PMID- 3331201 TI - Normal sexual maturation. AB - Puberty represents a period of important changes which lead to sexual maturation and active functions of reproduction. Sequences of the somatic and hormonal changes are presented both in boys and girls. Mean ages of onset of puberty are 10.9 and 11.2 in girls and boys, respectively. Menarche occurs at a mean age of 13.4 years and may be related to a critical weight. In boys, testicular growth above 4 cm2 or 4 ml is the first clinical sign of gonadal pubertal maturation. In girls, the first sign is the budding of the breast. At onset of puberty, the hypothalamus resumes a marked pulsatile secretion of gonadotropin-releasing hormone, leading to an increased secretion of pituitary gonadotropins which in turn stimulate the gonadal functions, i.e. the secretion of testosterone or estradiol and maturation of the spermatogenesis or the ovarian follicle. Neuroendocrine factors which probably control the onset of puberty are numerous: adrenergic or dopamine neurotransmitters, endogenous opioids, melatonin from the pineal gland. Gonadal maturation (gonadarche) is preceded in the infant by a postnatal surge of luteinizing hormone and at age 7-8 years by an adrenal maturation called adrenarche. PMID- 3331202 TI - Delayed sexual maturation. AB - Absence of any sign of gonadal development (i.e. increase in size of the testes or presence of breast budding) before the age of 13 years in girls and 14 years in boys represents the condition of delayed sexual maturation. After this age, the patient should be thoroughly clinically examined and a basic biological work up should be performed. Pathological conditions such as hypergonadotropic hypogonadism with a bone age usually greater than 13 years can be easily diagnosed. Hypogonadotropic hypogonadism is more difficult to differentiate from delayed adolescence of good prognosis. Means of diagnosis as well as therapy are discussed. In addition, micropenis and primary amenorrhea are frequent clinical observations. PMID- 3331203 TI - Catch-up growth. AB - We describe the phenomena of catch-up and catch-down growth. These are normal physiological responses in both endocrine and non-endocrine diseases of childhood. Evidence suggests that catch-up growth is controlled by a centre in the central nervous system and that it is not dependent on increased growth hormone secretion. PMID- 3331204 TI - Changes of skinfold thickness during puberty induced by pulsatile gonadotrophin releasing hormone therapy. AB - We have analysed the changes in triceps and subscapular skinfold thickness ratios of 66 (46 male, 20 female) children with constitutional delay of growth and puberty who progressed through puberty spontaneously and 16 (7 male, 9 female) children with delayed puberty who were treated with pulsatile gonadotrophin releasing hormone (GnRH). The pattern of change in skinfold thickness in both groups were identical and indistinguishable from standards of normal children when later chronological ages of the patients were allowed for. We observed a decrease in skinfold ratio just prior to the onset of puberty in boys, and such an assessment may be a useful early predictor of the onset of puberty. Our data provided further evidence that all aspects of human puberty are entirely GnRH dependent. PMID- 3331205 TI - Effect of asthma on growth and puberty. AB - It is now known that asthma has no direct influence on growth in height but is significantly associated with delay in the onset of puberty. The pre-adolescent physiological deceleration of growth velocity that occurs in these children gives the impression of growth retardation. Once puberty has finally begun, however, complete catch-up growth results in the attainment of the predicted adult height. A consequence of pubertal delay is increased emotional stress in an already unstable adolescent. This may adversely affect disease control and drug compliance. The main cause of growth retardation in the past was the long-term prophylactic use of oral corticosteroids. Since the advent of inhalation steroids, this has no longer been a problem. PMID- 3331206 TI - Short stature and pubertal delay in cystic fibrosis. AB - Survival of the patient with cystic fibrosis has been considerably extended in the last two decades due to improved therapy of pulmonary infection, nutritional management, and an organized system of centralized care. Psychological and social aspects of cystic fibrosis may be intensified during adolescence: developing independence in the face of required daily care; developing self-esteem in the face of illness-associated problems such as discolored teeth, malabsorption, short stature, and cough; and participating in group activities despite physical limitations and the disruption in peer relationships when recurrent acute illness is interposed. Pubertal delay is more common in the cystic fibrosis population than the general population, and attendant psychologic dysfunction may be particularly common in males. Comparative studies suggest that this pubertal delay is a function of malnutrition rather than intrinsic to the disease. Normal growth potential may be postulated from somatomedin studies and has been demonstrated in patients treated with long-term aggressive nutritional management. Intervention utilizing testosterone enanthate in males with cystic fibrosis and pubertal delay has resulted in improved rate of growth, progression through puberty, and self-image. PMID- 3331207 TI - Isosexual precocious puberty. AB - Isosexual precocious puberty refers to the appearance of phenotypically appropriate secondary sexual characteristics before age 8 years in girls and before 9 years in boys. Isosexual precocity may be categorized into several subgroups depending upon etiology and clinical course: true and complete isosexual precocity refers to early activation of the intact hypothalamic pituitary-gonadal axis; pseudo-isosexual precocity is due to sex steroid production which is independent of hypothalamic-pituitary regulation; incomplete forms of isosexual precocity include premature thelarche and premature adrenarche. Etiologic, diagnostic and therapeutic considerations are discussed. PMID- 3331209 TI - The spectrum of avulsion and avulsion-like injuries of the musculoskeletal system. AB - Awareness of the radiographic appearances of various avulsion injuries helps the radiologist to arrive at an accurate diagnosis without unnecessary patient workup. PMID- 3331208 TI - Ultrasound case of the day. Duplication artifact (mirror image artifact). PMID- 3331210 TI - Acquired immunodeficiency syndrome. AB - The acquired immunodeficiency syndrome (AIDS) was recognized as a distinct clinical entity in 1981 and was characterized by unexplained opportunistic infections and an aggressive form of Kaposi's sarcoma. High risk groups for contracting AIDS include homosexual men, parenteral drug users, hemophiliacs, recipients of blood and blood products, and heterosexual contacts of such individuals. Immunologic abnormalities associated with AIDS include lymphopenia, functional T-cell deficits, B-lymphocyte defects, and various serologic abnormalities. The causative virus has been identified as the human T lymphotropic virus/lymphadenopathy associated virus (HTLV-III/LAV). AIDS represents the severe end of the clinical spectrum of infection with HTLV III/LAV. Other manifestations are asymptomatic carriage, generalized lymphadenopathy, and a set of non-specific symptoms, termed the AIDS-related complex (ARC). Although seen predominantly in the United States, AIDS has a world wide occurrence. No known therapy for AIDS exists. Research efforts are being directed at antiviral therapy, immunorestoration and the development of a vaccine. PMID- 3331211 TI - Advanced transitional cell bladder cancer: a treatable disease. AB - Although metastatic bladder cancer is difficult to treat effectively, chemotherapy combinations and schedules have emerged recently that can result in long-lasting complete responses in some patients. Response rates, response durations, and survival patterns of the entire patient population are, however, unsatisfactory. Whereas survival times of these patients following therapy with cisplatin alone or in combination with other drugs are not significantly different, complete response rates are higher and disease-free survival is longer when combinations are used. Higher dosages are associated with better response rates but also with substantial toxicity. Extensive local pretreatment or prior systemic chemotherapy reduces the likelihood of clinically meaningful disease response. Several adjuvant studies have demonstrated an advantage in length of disease-free survival for chemotherapy-treated patients when compared to those who are observed following operation. Metastatic transitional cell bladder cancer is a chemotherapeutically treatable malignancy. Locally advanced disease may be most effectively treated by aggressive surgery followed by cisplatin-based combination chemotherapy. The highest response rates and longest disease-free survivals are uniformly associated with aggressive and prolonged multidrug therapy. PMID- 3331212 TI - EAR method: an alternative method of bone grafting following bone tumor resection (a preliminary report). AB - The EAR (Excision, Alcoholization, Replantation) method consists of a proper tumor resection, removal of tumor tissue extracorporally, soaking the residual bone shell in 95% alcohol for half an hour, and replantation in situ, the cavity being filled with bone graft or bone cement. Eighty-three cases were treated in this manner, of which 95% were followed for 2 years or more, with complete success in cases with IA lesions and no recurrence in two-thirds of those with IB IIB lesions. Experimentally, it is proved that alcohol can kill tumor cells completely without interfering with osteogenesis. The joint cartilage, although degenerated, is replaced by newly formed fibrocartilage, thus preserving joint function. PMID- 3331213 TI - [Technetium 99m-DTPA radioaerosol in patients with lung disease induced by amiodarone. Preliminary results]. PMID- 3331214 TI - [Role of Triatomidae in the transmission of infection by hepatitis virus type B, in different clinical forms of the disease]. PMID- 3331216 TI - [Historiography of 2 important zoonoses: trichinosis and leprosy (porcine cysticercosis). I. Trichinosis]. PMID- 3331215 TI - [Apparatus for the measurement of the rupture strength of an intestinal anastomosis]. PMID- 3331217 TI - Mechanism of myelofibrosis in chronic myeloproliferative disorders. PMID- 3331218 TI - Inhibition of in vitro splicing of a mouse insulin pre-mRNA by covalent cross links in the intron region. AB - Recent studies have indicated that in vitro splicing of a mouse insulin pre-mRNA by a HeLa cell nuclear extract is accompanied by the unwinding of substrate RNA. The present experiments were performed to determine whether this melting of the secondary structure of the precursor RNA is essential for the splicing reaction. 32P-labelled mouse insulin pre-mRNA synthesized in vitro in a SP6 transcription system was cross-linked with aminomethyltrimethyl psoralen and fractionated by polyacrylamide gel electrophoresis. RNA species containing different intramolecular cross-links were eluted from the gel and the sites of cross-links were mapped by primer extension analysis using synthetic oligonucleotide primers. Under conditions that allow accurate in vitro splicing of intact pre-mRNA, precursor molecules with psoralen cross-links within their intron region were not spliced by a HeLa cell nuclear extract. This observation strongly supports the assumption that unwinding of precursor RNA molecules is necessary for the splicing reaction. PMID- 3331219 TI - Pathophysiology of constipation. PMID- 3331220 TI - [Chronic idiopathic intestinal pseudo-obstruction. Presentation of a case and review of the literature]. PMID- 3331221 TI - Pseudotumoral primary sclerosing cholangitis. Report of two cases and review of the literature. PMID- 3331223 TI - Angiography in thyroid and parathyroid pathology. PMID- 3331224 TI - Magnetic resonance of thyroid diseases. PMID- 3331222 TI - Thyroidal echotomography. PMID- 3331226 TI - Cancer of the thyroid body: indications for surgery (with the exclusion of medullary carcinomas). PMID- 3331225 TI - Nodular thyroid disease and cancer. AB - Different possibilities of solitary or multinodular involvement of the thyroid gland are described. Because of the broad spectrum of malignancy there exists a controversy and widespread divergence of opinion regarding the incidence, malignancy, classification and treatment of thyroid cancer. PMID- 3331227 TI - Attitude to cervical lymphatic nodes in thyroid-cancer surgery. PMID- 3331228 TI - Surgery in multinodular goitre. PMID- 3331229 TI - Surgery of substernal goiter. PMID- 3331230 TI - Postoperative monitoring and treatment. PMID- 3331232 TI - Hypoparathyroidism. Its prevention, and the indications and technique for parathyroid autotransplantation. PMID- 3331231 TI - Vocal folds bilateral paralyses in closed position. PMID- 3331233 TI - Plasma insulin and C-peptide responses to oral glucose load after physical exercise in men with normal and impaired glucose tolerance. AB - Blood glucose, plasma insulin and C-peptide responses to oral glucose tolerance test (OGTT) were studied under basal conditions and immediately after 90-min exercise (60% VO2 max) in nondiabetic subjects with normal or impaired glucose tolerance. During the postexercise recovery blood glucose response to OGTT was increased in normal subjects and markedly decreased in those with impaired glucose tolerance, while insulin and C-peptide responses were diminished in both subgroups. The ratio of blood glucose to insulin was similarly elevated in all subjects. Comparing with basal conditions no significant changes were found in C peptide to insulin ratio in response to OGTT after exercise, although a tendency towards an elevation of this ratio was noted in the subjects with impaired glucose tolerance. The data indicate that the reduced insulin response to OGTT during postexercise recovery in healthy subjects is due to diminished insulin secretion without any substantial changes in the hormone removal from blood, whereas in the glucose intolerant men the latter process may be enhanced. PMID- 3331234 TI - The effect of repeated administration of insulin on pain threshold and gamma aminobutyric acid level in mouse brain. AB - In experiments on male Albino-Swiss mice weighing 18-22 g insulin given in doses of 2 i.u./kg caused no change in the time of reaction to pain, while the same dose administered daily for 7 days potentiated the analgesic action of morphine (3 mg/kg s.c.). Glucose caused no change in this effect of insulin. After 14 days of insulin treatment the time of reaction to pain in the animals subjected to the action of morphine returned to its initial value. Twenty-four hours after the last administration of morphine the level of gamma-aminobutyric acid (GABA) was found to be decreased in the animals receiving insulin with glucose. These results suggest that the central action of insulin is dependent not only on hypoglycaemia produced by it, but may be due also to its direct action on the central structures and an indirect action mediated by its effect on other neurotransmitter systems. PMID- 3331235 TI - Estrogen receptors as nuclear proteins. PMID- 3331237 TI - Studies on malaria. In honour of Professor B. G. Maegraith on his 80th anniversary. PMID- 3331236 TI - Bioassays. Patents and literature. AB - Bioassays, including immunoassays, enzyme assays, and assays using enzyme electrodes, and nucleic acid hybridization probes have been the subject of considerable industrial and academic research. New bioassay methods have applications in the medical, chemical, pharmaceutical, and food products industries. Recent US patents and scientific literature on a variety of new bioassay methods are surveyed. A description of these patents and a list of references are given. PMID- 3331238 TI - Unde venis viator et quo vadis? PMID- 3331239 TI - Malaria in Africa south of the Sahara. PMID- 3331240 TI - Malaria and child health. PMID- 3331241 TI - The cultivation of Plasmodium falciparum: applications in basic and applied research on malaria. PMID- 3331242 TI - The liver in malaria with special reference to the exoerythrocytic phase. PMID- 3331244 TI - Capillary permeability function in malaria. PMID- 3331243 TI - Common genetic disorders of the red cell and the 'malaria hypothesis'. PMID- 3331245 TI - Acute renal failure in malaria and some febrile and other illnesses. PMID- 3331246 TI - The bone marrow of non-immune Europeans in acute malaria infection: a topical review. PMID- 3331247 TI - Monokines and lymphokines in malarial pathology. PMID- 3331248 TI - Biochemical approaches to research in malaria. PMID- 3331249 TI - The pathophysiology of malaria after Maegraith. PMID- 3331250 TI - The treatment and prophylaxis of malaria. PMID- 3331251 TI - Currently important antimalarial drugs. PMID- 3331252 TI - The antimalarial action of chloroquine and mechanisms of resistance. PMID- 3331254 TI - Malarial immunity: current trends and prospects. PMID- 3331253 TI - The chemotherapy of rodent malaria. XLII. Halofantrine and halofantrine resistance. AB - As a blood schizontocide, halofantrine is about three times as active against a drug-sensitive line of Plasmodium berghei (N strain) as chloroquine, but it lacks any causal prophylactic effect. This activity is retained against parasites highly resistant to primaquine, cycloguanil, pyrimethamine, sulphaphenazole and menoctone. A marked resistance to halofantrine is shown by parasites resistant to mefloquine, quinine, chloroquine and amodiaquine, although the moderately chloroquine-resistant 'NS line' is sensitive. The artemisinin-resistant line shows a moderately reduced response. A high level of resistance was rapidly developed in the 'NS line' to halofantrine (NS/HAL line) but not in the N strain (N/HAL). The NS/HAL line was cross-resistant to mefloquine, amodiaquine and, to a lesser degree, artemisinin, but remained sensitive to chloroquine and quinine. The implications to a lesser degree, artemisinin, but remained sensitive to chloroquine and quinine. The implications of these observations for the possible future clinical deployment of halofantrine are discussed, and emphasis is laid on the need to find means of impeding the resistance to it of Plasmodium falciparum. PMID- 3331255 TI - [Definition and declaration of birth in Belgium. Juridical, administrative and medical problem]. PMID- 3331256 TI - Safety aspects of magnetic resonance imaging and magnetic resonance spectroscopy applications in medicine and biology: I. Biomagnetic effects. PMID- 3331257 TI - [Mitral valve prolapse: comparative aspects in man and woman]. PMID- 3331258 TI - Hypertension--a paramount cardiovascular risk-factor in the Western world. PMID- 3331259 TI - [Mitral valve prolapse and infectious endocarditis. Bases for indications in antibiotic prophylaxis]. PMID- 3331260 TI - [Coronary disease. 2 centuries of challenge]. PMID- 3331261 TI - [Unstable angina: identification of subgroups with high risk of cardiac sudden death]. PMID- 3331262 TI - [Therapeutic schedules in essential arterial hypertension]. PMID- 3331263 TI - The viral factor in childhood asthma. AB - Independently of the important role the infections bacterial factor plays in childhood asthma, many authors have considered the virus the primary triggering factor of bronchospasm. This latter factor has been so exaggerated that some authors have even conceded it the maximum importance. In studies carried out with a more numerous population than in those works presented so far, controlling the presence of antibodies during the crisis and a week later in serum from asthmatic children, the authors found that only 13.5% presented specific antibodies against one or two of the sixteen viral antigens studied. These children at the same time developed a bacterial infection which remitted with antibiotic therapy, with the consequent disappearance of the asthma. In etiopathological studies realized in 700 children it was equally confirmed that the bacterial factor was involved in 90% of the cases, in the sense of a sinopulmonary syndrome. More profound studies are needed to clarify this point which is held in little consideration by many clinicians. PMID- 3331264 TI - The effect of prostacyclin on asthma precipitated by aspirin. AB - Inhibition of prostacyclin biosynthesis by aspirin might be expected to promote asthmatic attacks in aspirin-intolerant patients. In vitro, prostacyclin inhibits generation of leukotrienes and opposes their bronchoconstrictive action. In a double-blind study we compared the effects of intravenous infusions of prostacyclin with those of its solvent on bronchoconstriction provoked by threshold doses of aspirin in 9 known aspirin-sensitive asthmatics. The intensity of bronchial obstruction precipitated by aspirin was similar during prostacyclin and placebo infusions. There was no difference in other symptoms of intolerance, except for rhinorrhea which seemed accentuated by prostacyclin (possibly because of nasal vasodilatation). Our results suggest that either the inhibitory effects of prostacyclin on leukotrienes described in vitro do not apply in vivo, or the importance of leukotrienes have been overestimated in this type of asthma. Idiosyncrasy to aspirin, which affects 5-10% of adult asthmatics, was thought several decades to be of allergic background, while in fact numerous and extensive immunological studies ruled out typical IgE--mediated allergic mechanisms for aspirin--induced asthma. In 1974, at the Department of Allergy and Clinical Immunology in Cracow, a novel hypothesis was put forward. If stated that in sensitive patients, precipitation of asthmatic attacks by aspirin and by certain nonsteroidal antiinflammatory drugs (NSAID) results from inhibition of specific enzyme in the bronchi, cyclooxygenase, leading to an imbalance of prostanoids in the respiratory tract. Over the years which followed evidence has been accumulated which strongly support this hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331266 TI - [Determination of specific serum IgG4 by an enzyme immunoassay]. AB - Specific series IgG4 titrate is realized now with a enzymo-immunologic using "double sandwich" method with allergen and patient serum in presence of a conjugate with peroxidase monoclonal Anti IgG4. Calibration obtains with a standard curve, is realized with a monoclonal IgG4 concentration is known. The first tests are in favor of correlation between specific IgG4 specific, IgE and in another way, the increase of specific IgE and specific IgG4 in a venom immunotherapy. PMID- 3331265 TI - Monosodium glutamate-induced asthma: study of the potential risk of 30 asthmatics and review of the literature. AB - Monosodium glutamate is a physiological nutrient, and food additive used as a taste enhancer. Several cases of intolerance to MSG in patients with asthma and with a Chinese Restaurant Syndrome have been published. A high dose of 2.5 g was tested in 6 healthy controls and 30 asthmatics (7: allergic asthma; 15: intrinsic asthma with intolerance to aspirin; 8: intrinsic asthma with aspirin intolerance, intolerance to alcohol or to food additives). Two patients presented with a mild bronchospasm, occurring 6 to 10 hours after the ingestion. Different mechanisms are discussed. A cholinergic mechanism might be incriminated, either due to stimulation of the synthesis of acetylcholine, or due to a vagal reflex elicited by a reflux esophagitis. However, a high vagal hyperreactivity seems to be needed for the occurrence of asthma. It is concluded that a very small subset of patients with intrinsic asthma might present with an intolerance to MSG if high doses are consumed. PMID- 3331267 TI - [Blocking antibodies and desensitization]. AB - Specific IgG1 and IgG4 antibodies synthesis is well known after immunotherapy. IgG4 may act as "blocking antibodies" and IgG1 may inhibit the synthesis of specific IgEs. However, the dosage of these antibodies by a technic using a solid phase is sometimes unreliable. Moreover these technics do not appreciate the functional activity of IgGs, which is best studied by incubating the allergen with IgG and then, measuring the allergen potential (using histamine release or basophil degranulation). Our studies regarding rush immunotherapy with mites by measuring the human basophil degranulation indicate the following: 1. the blocking activity is induced by rush; 2. is significant the 7th day; however there are some individual variations which do not depend on the cumulate dose of the allergens; 3. it is due to IgG and not to IgA or IgM (fractionation on column); 4. it disappears under the effect of the anti-human-IgG antibodies; 5. it increases with the time of incubation but it appears significant activity even at time 0 min. We conclude that the role of these IgGs during rush to mite is fundamental. PMID- 3331268 TI - [Bronchial hyperreactivity in asthma at high risk of sudden death]. AB - Sudden severe life threatening attack (SSA) may occasionally develop in some patients who have had until that event a mild asthma without detectable baseline airway obstruction. Airway responsiveness (AR) measurement could be a useful mean to characterize or identify them. No data exist regarding the baseline non specific AR of such patients. We studied 5 patients having had a SSA during their past few weeks. Methacholine (MCH) challenges were performed only when standard pulmonary function tests were close to normal (FEV1 greater than or equal to 80% pred.); the patients were off medication at the time of MCH challenges. 3 to 8 evaluations were performed over a time span of 4 to 24 months. The level of AR ranged from moderately increased (PC20 = 24 mg/ml). Mean PC20 was 7,8 mg/ml. This level of AR did not differ significantly from that found in a population of 67 mild asthmatics who also were evaluated in the absence of baseline bronchial obstruction and were off medication (PC20 = 5,5mg/ml). In any individual asthmatic having sustained SSA, AR was strikingly stable. However in two patients we detected a marked decrease in PC20 which was followed within 2 weeks by a SSA. We conclude that: 1. Asthmatics who have had SSA do not demonstrate particularly AR, which is not related to the severity of their asthma. 2. Baseline AR is usually stable. 3. The measurement of AR in these patients is not very useful, specially for substantiating medication needs. 4. A marked increase in AR can be observed before SSA. PMID- 3331269 TI - [Male-female recognition during sexual reproduction in flowering plants]. AB - In flowering plants, the recognition reactions occur between male and female partners at the stigma level or along the style and in the embryo sac between the gametes. The study of these biological events implies to check the viability of the two partners. Interacting molecules are glycoproteins. A cDNA coding for the stigma protein molecules has recently been cloned. The specific pollen molecules have been also characterized. They are glycoproteins which are localized at the periphery of the grain and rapidly diffuse. These recognitive molecules present some analogies with pollen allergens. PMID- 3331270 TI - [Botany of Artemisia]. AB - Artemisia vulgaris L. belongs to the family Compositae, sub-family Corymbiferae. The genus Artemisia groups together almost 200 species, the most of them are native of Eurasia and Northern America steppe regions. Artemisia are wind pollinated plants, the flowers do not secrete any nectar and are not visited by bees. Two species of Artemisia are widely spread through the Lyon region and are with Ambrosiaceae to blame for the pollinosis in summer and autumn: A. annua and A. vulgaris. PMID- 3331271 TI - [A glimpse of the history of the genus Artemisia from pollen analyses]. AB - The first certain data about the pollen grains of Artemisia have been found about the Middle Miocene. A review of the recent works concerning Western Europe and Northern Africa allows us to have some confirmation of this point of view. The pollen of Artemisia is appearing in the Miocene (Serravallian) with very poor amounts, the first important spreading of this plant, as revealed by sporopollinic analysis, comes near the Tertiary-Quaternary boundary at the time of an important deterioration of the climate. For the Quaternary, Artemisia is often present with low percentages and is only developing during the glaciation. In the Upper Quaternary, after the glaciation, the vegetation with Artemisia especially widens because of the man influence: clearing and/or breeding. This plant, which actually gives us many environmental problems, seems to have been differentiated a short time ago. It is a wind-pollinated vegetable, perhaps issued from the Compositae Anthemidae which have an echinulate pollen grain, the spines have been reduced almost to relics by adaptation to the wind dispersion. PMID- 3331272 TI - The child with group A streptococcal pharyngitis. PMID- 3331273 TI - Update on infectious diarrhea. PMID- 3331274 TI - Infections associated with long-term intravascular and cerebrospinal fluid shunt catheters. PMID- 3331275 TI - Lyme disease: epidemiology, etiology, clinical spectrum, diagnosis, and treatment. PMID- 3331276 TI - Bacteremia in the febrile child. PMID- 3331277 TI - Rapid viral diagnostic techniques. AB - The application of viral diagnosis to clinical medicine is approaching a critical period in which greater emphasis will be placed on altering patient care as a result of viral identification. Although isolation of viruses in tissue culture is the "gold standard" to which all other methods of viral identification are compared, the expense in terms of cost and technical time required as well as the time necessary for specific viral isolation has severely limited the use of viral diagnosis in clinical medicine. The concomitant development of rapid viral diagnostic procedures with the increased availability of anti-viral therapy, promises to alter how patients will be managed in the future. The greatest emphasis for rapid viral diagnosis has been placed on viral detection directly from clinical specimens since these procedures eliminate the need to cultivate the virus. Methods for direct detection of viral antigens in clinical specimens include electron microscopy and a wide range of immunologic assays. The extraction of nucleic acid directly from clinical specimens and hybridization of this DNA to specific viral probes also provides for virus identification without the need to culture the virus. Currently, many of the rapid diagnostic procedures discussed are performed only in research laboratories. Over the next several years, however, methods of antigen detection using EIA procedures and detection of viral-specific nucleic acid promise to alter how we study and diagnose viral infections. PMID- 3331278 TI - Varicella zoster infections of the fetus, neonate, and immunocompromised child. PMID- 3331279 TI - Epidemiology and immunology of Hemophilus influenzae type B infections in childhood: implications for chemoprophylaxis and immunization. PMID- 3331280 TI - Urinary tract infection in children. AB - Based on what is known of the pathogenesis of renal scarring, several therapeutic goals are important and are summarized in Figure 4. First, in children less than 5 years of age, and particularly neonates, a high index of suspicion must be combined with appropriate diagnostic techniques, including suprapubic aspiration if necessary, to obtain rapid and accurate diagnosis of urinary tract infection, thereby minimizing therapeutic delay. Although therapy can be started with broad spectrum antibiotics, culture and sensitivities are important to assure adequate antimicrobial therapy. Second, given the high incidence of vesicoureteral reflux in children with urinary tract infections, all children less than 5 years of age should have a VCUG and IV pyelogram shortly after resolution of the acute infection. In children more than 5 years of age, boys should be studied, given the very low incidence of urinary tract infection in males, and the high probability of urologic disease. Afebrile girls more than 5 years of age are exempted from diagnostic evaluation of the first episode of infection. Subsequent episodes should be investigated. Third, children with reflux should receive continuous antibiotic prophylaxis until age 6 to 8 years or until reflux resolves. Yearly evaluations are performed with radionuclide cystography, which is a nontraumatic sensitive means of detecting reflux, requiring less radiation than VCUG. Individuals of any age with recurrent urinary tract infections without reflux may benefit from a 3- to 6-month course of antimicrobial prophylaxis. Finally, antibiotic therapy should be appropriate and adjusted as necessary based the susceptibility of the bacterial pathogen. In older girls with simple uncomplicated urinary tract infections, single-dose therapy may be adequate. Younger children at increased risk for renal scarring should be treated more conservatively, receiving a 10-day course of therapy. PMID- 3331281 TI - Childhood tuberculosis. PMID- 3331282 TI - Pulmonary infections in the immunocompromised child. PMID- 3331283 TI - Infections in day-care centers: etiology, prevalence, and management. PMID- 3331284 TI - Routine immunizations and the immunosuppressed child. PMID- 3331285 TI - Reassembly of active 30S ribosomal subunits with an unmethylated in vitro transcribed 16S rRNA. AB - A plasmid has been constructed, which contains the 16S ribosomal RNA gene of Escherichia coli immediately downstream from a phage T7 promoter. In vitro transcription of this gene by RNA polymerase of the T7 phage yielded an unmethylated 16S rRNA that could be used for the assembly of functional 30S subunits. These subunits when assayed in a poly(U)-directed translation assay, were as active as 30S subunits reconstructed with native 16S rRNA. This system opens the possibility of investigating the role of the methylations of the rRNA and the functional consequences of site-directed mutagenesis in a rRNA gene. An application of this system was provided by generating a 16S rRNA transcript shortened by about 30 nucleotides at the 3' end. This truncated rRNA could be reassembled into 30S subunits, about 70% as active as 30S subunits reconstructed with the full-length 16S rRNA transcript. PMID- 3331286 TI - Identification of a human osteosarcoma-associated glycoprotein with monoclonal antibodies: relationship with alkaline phosphatase. AB - The molecular nature of an osteosarcoma-associated antigen was investigated with the three monoclonal antibodies Ost6 (immunoglobulin (IgG1), Ost7 (IgG1), and Ost15 (IgG2a), which selectively react with frozen sections of osteosarcoma and chondrosarcoma tissues. When tested with a panel of 41 human cell lines in the mixed hemadsorption assay, the antibodies reacted similarly with three of six osteosarcomas, one choriocarcinoma, one teratoma, and one osteoblast-like culture, but failed to react with 32 lines of normal and other tumor cell types. Immunoprecipitation plus sodium dodecyl sulfate (SDS)--polyacrylamide gel electrophoresis and sequential immunoprecipitation studies revealed that in [35S]methionine- or [14C]glucosamine-labelled osteosarcoma cells the three antibodies detected a single glycoprotein, with an apparent molecular mass of 86 kilodaltons (kDa), which was not affected by reducing conditions. Tunicamycin treatment and pulse-chase experiments showed glycosylation of this molecule to be N-linked; it arose from a 54-kDa polypeptide precursor. Alkaline phosphatase activity was detected in the material rich in 86-kDa molecules that was immunoprecipitated from serologically reactive cell lines with each antibody. These antibodies also cross-reacted with two isoenzymes of alkaline phosphatase (strongly with the liver and bone, and moderately with the placental isoenzyme), but not with the intestinal form. PMID- 3331287 TI - [Comparative study of the changes in blood gastrin, insulin, and glucose in non steroidal anti-inflammatory agent-induced gastroduodenal diseases treated with prostaglandin analogs of the E2 series]. PMID- 3331289 TI - [Blood levels of activated renin, aldosterone, catecholamine in congestive heart failure. I. Role of the adrenergic and dopaminergic systems]. PMID- 3331288 TI - [Changes in circulating lymphocytes and "E" rosettes in patients with colonic neoplasms treated with transfer factor]. PMID- 3331291 TI - Modern aspects of drug treatment in children with epilepsy. AB - This review paper deals with the drug therapy of children with epilepsy with special reference to diagnosis and differential diagnosis of epilepsy, measures before and at the initiation, follow-up, and withdrawal of the therapy. The updated aspects on the medication of various seizure types are discussed in detail. PMID- 3331290 TI - [Blood levels of activated renin, aldosterone, catecholamine in congestive heart failure. II. Effects of dopaminergic stimulation with a dopamine agonist: ibopamine]. PMID- 3331292 TI - Production of monoclonal antibodies against phloem-limited prokaryotes of plants: a general procedure using extracts from infected periwinkles as immunogen. AB - Using Spiroplasma citri-infected periwinkle extracts as the source of antigens, together with monoclonal antibody technology, we determined the conditions for mouse immunization and developed a screening assay to detect those hybridomas which produce immunoglobulins specifically directed against the pathogen. PMID- 3331293 TI - Monoclonal antibodies against the bacterial-like organism associated with citrus greening disease. AB - Hybridoma clones secreting specific monoclonal antibodies (mAb) against the bacterium-like organism associated with citrus greening disease were produced from homogenates of infected phloem tissues used as immunogens in mice immunizations. Differential ELISA and immunofluorescence were used to screen for hybridomas secreting mAb against the greening organism (GO). Two such hybridoma clones were obtained. The mAb were specific for the GO. No cross-reactions were seen with any of the other phloem-limited prokaryotes tested nor with healthy plant material. PMID- 3331294 TI - Evaluation of the Biken test to detect heat-labile (LT) enterotoxin produced by porcine and human Escherichia coli strains. AB - Fifty-seven strains of enterotoxigenic Escherichia coli isolated from humans and pigs and producing thermolabile (LT) enterotoxin were used to ascertain the efficiency of the Biken test compared to the passive immune haemolysis test (PIH), considered as very sensitive for detecting that enterotoxin. The two assays were carried out using anti-porcine (anti-LTp), anti-human (anti-LTh), anti-cholera toxin (anti-CT) and anti-choleragenoid (anti-Cg) antisera. Our results showed that the Biken test was very irregular, with many false-negative results. Positive results (ranging from 78.9 to 22.8) were dependent upon the antiserum used. Conversely, the PIH test was much more efficient in the detection of LT, since 100% of the LT+ strains were positive in this test whatever the antiserum used. PMID- 3331296 TI - The behavioral treatment of Raynaud's disease: a review. AB - Raynaud's disease is a peripheral vascular system disorder characterized by episodes of vasoconstriction in the hands and feet resulting in a lowering of skin temperature and pain. Recent studies are reviewed that focus on the behavioral treatment of Raynaud's disease--in particular, biofeedback and autogenic training. Methodological problems and other difficulties include the measurement of skin temperature, schedules of reinforcement/feedback, and characteristics of the experimenter and subject. Studies in this area indicate some promise for certain behavioral interventions, especially finger temperature biofeedback under cold stress conditions. On the other hand, further research is needed to clarify the mechanisms, especially that of vasodilation, and the applications of temperature biofeedback, as well as the role of attitudinal, interpersonal, and cognitive factors. PMID- 3331295 TI - Treponemal antigens detected by immunoblotting with serum and CSF antibodies of neurosyphilitic patients. AB - Treponemal-antigen-eliciting antibodies in neurosyphilis were investigated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis immunoblotting with 17 sera and cerebrospinal fluid (CSF) (16 pairs) from 10 neurosyphilitic patients. Sera and CSF detected identical proteins. IgG antibodies in sera and CSF mainly revealed Treponema pallidum proteins of MW 48, 45, 38 and 37 Kd, and T. phagedenis proteins of MW 59, 54, 41, 40, 35 and 33 Kd. Few proteins were detected by IgM antibodies. Although no particular protein elicited antibodies specific for neurosyphilis, the immunoblot detection of antibodies to T. pallidum or T. phagedenis antigens in CSF or sera should be useful as a diagnostic tool for neurosyphilis. PMID- 3331297 TI - Relaxation with biofeedback-assisted guided imagery: the importance of breathing rate as an index of hypoarousal. AB - Fifteen men and 35 women, suffering from a number of psychological and somatic disorders, were taught to relax by biofeedback-assisted deep-diaphragmatic breathing together with guided mental imagery. No instructions were given about rate. Breathing rate and pattern, PETCO2, and EEG were monitored before training and after the first three 2-minute training trials (session 1). In 27 subjects (54%), breathing patterns and rate were noted to resemble those reported by meditation practitioners (3 to 5 b/min). The PETCO2 and EEG changes support a hypothesis of metabolic hypoarousal. Four subjects spontaneously reported experiencing altered awareness. A centrally mediated hypoarousal response is tentatively implicated. PMID- 3331298 TI - A multiple-baseline evaluation of the treatment of subjective tinnitus with relaxation training and biofeedback. AB - Six subjects with subjective tinnitus received training in relaxation techniques and EMG and thermal biofeedback in a multiple-baseline across-subjects design. Daily tinnitus disturbance and sleep disturbance diaries were kept throughout. Audiological and psychological evaluations were made at various treatment phases. At posttreatment assessment, subjects also completed global ratings of their perceived improvement in ability to cope with the tinnitus, stress caused by the tinnitus, and severity of the tinnitus, as well as their overall satisfaction with the treatment. Ratings on the global scales were generally very positive. By way of contrast, the daily diary results revealed little if any treatment effect. The implications of these disparate results are discussed. PMID- 3331299 TI - What is an adequate length of baseline in research and clinical practice with chronic headache? AB - We examined the representatives of baseline headache diary recording periods of 1, 2, 3, and 4 weeks for three kinds of headache disorder--tension, migraine, and combined migraine and tension. For research purposes at pretreatment, 2 weeks of diary recording are preferable for tension headache, while at least 3 weeks are preferred for migraine and combined headache. At follow-up, 1 week of diary recording appears adequate for all three headache types. Recommendations are also made for clinical practice. PMID- 3331301 TI - [Torticollis of ocular origin. Introduction]. PMID- 3331302 TI - [Vertical torticollis and strabismus. A-V syndromes]. PMID- 3331300 TI - [Different types of torticollis in nystagmus patients]. PMID- 3331303 TI - Ethics committees in critical care. AB - Ethics committees have emerged as a way for institutions to evaluate and resolve some of the difficult decisions facing critical care medicine. This article examines their origin, scope, function, and potential problems. PMID- 3331304 TI - Ethical principles in critical care medicine. AB - This article identifies the ethical principles that have guided medicine since antiquity: beneficence, primum non nocere, patient autonomy, and respect for life and the quality of life. The author's basic premise is that many recently publicized ethical dilemmas are really not dilemmas--the knowledge of what is good or evil is not confused, contradictory, or absent. Instead, medicine's concern and responsibility to its patients is being clouded by legal, governmental, or societal concerns. PMID- 3331305 TI - The gift of life. Ethical problems and policies in obtaining and distributing organs for transplantation. AB - The supply of organs and tissues is inadequate to meet the need and demand for transplantation. The article argues for an effective and efficient system for obtaining cadaveric organs that can reduce and perhaps even eliminate scarcity, without violating the principles of justice and respect for persons. The article also examines policies and problems regarding living donors, and analyzes some issues in macroallocation and microallocation. PMID- 3331306 TI - Death, dying, and the brain. AB - These cases have been cited and these issues presented to make the point that principles are often out of phase with perceptions. The argument is not that principles should cede to perceptions. This would imply resignation to the unlikelihood of moral development. Neither do we claim that perceptions should simply and generally capitulate to principles. This could mean an intolerable dictatorship of one philosophy over experience. Clinical ethics is the challenge to integrate principles and perceptions continuously and critically in resolving value conflicts about the best care of individual patients. PMID- 3331307 TI - Critical care stress and burnout. AB - Burnout may be one of the most common problems affecting critical care physicians. Burnout can best be defined as disillusionment and a flattening of the effervescence of life. Recognizing the symptoms of burnout and the sources of stress enables one to incorporate preventive strategies and self-rescue techniques. PMID- 3331309 TI - Blood transfusions and Jehovah's Witnesses. The impact of the patient's unusual beliefs in critical care. AB - This article explains the belief of Jehovah's Witnesses regarding blood transfusions, and argues that a physician must ethically respect that belief. PMID- 3331310 TI - State-of-the-art and clinically applied pneumatic artificial hearts. AB - This article is intended to inform the reader of the current state of the art of pneumatically powered artificial hearts, including animal experiments and information available on 11 recipients of orthotopically placed devices. PMID- 3331308 TI - Patient autonomy, informed consent, and the reality of critical care. AB - The realities of serious illness and critical care environments often complicate our efforts to evaluate treatment refusal according to the doctrine of informed consent. However, health professionals must strive to use informed consent as the ultimate standard for both treatment and nontreatment decisions, by making continual efforts to communicate with patients, share information, and enhance their sense of autonomy and control. PMID- 3331311 TI - Mechanical-ventilatory cardiac support. AB - A large body of experimental data indicates that blood flows during CPR because of elevations of intrathoracic pressure and the uneven peripheral transmission of this pressure. Data from humans are less extensive, but also strongly support the mechanism of intrathoracic pressure. It should be remembered that the intrathoracic pressure and direct cardiac compression hypotheses are not mutually exclusive, and that effective CPR is above all dependent on vigorous chest compression. Maintenance of sternal displacement for 40% to 50% of each compression-release cycle, intense alpha-adrenergic stimulation, and avoidance of vasodilators are also essential to the maximization of cerebral and myocardial perfusion. Whether movement of blood by manipulation of intrathoracic pressure can be applied successfully to other disease states is unknown. What is established is that vigorous chest compression, adequate ventilation, and generous use of epinephrine, along with prompt defibrillation, form the basis of an effective strategy for life support. Provision of chest compression and mouth to-mouth ventilation by bystanders prior to delivery of definitive care has been shown to increase survival rates from 8% to 36% in Columbus, Ohio, and from 21% to 43% in Seattle. Bystander-initiated CPR also reduced the frequency of neurologic impairment at the time of hospital discharge from 55% to 4% in the Seattle experience. For patients receiving the full program of chest compression, ventilation, drug therapy, and defibrillation, resuscitation rates in excess of 50% have been reported in both in-hospital and out-of-hospital arrests. Of those who survive to hospital discharge, 6-month survival rates of 80% have been reported from these patients cohorts, with return-to-work rates of 70%. These data demonstrate that CPR is an effective means of supporting the circulation during cardiac arrest. The majority of survivors return to a meaningful existence, and the technique has not burdened society with a large load of neurologically impaired patients. Thus, CPR is very much worthy of the full attention and support of the medical community. PMID- 3331312 TI - Strategy for treatment of acute evolving myocardial infarction with pulsatile left heart assist device. Can this modality increase survival and enhance myocardial salvage? AB - This article describes the technique of left heart bypass in the treatment of both experimental and clinical acute myocardial infarction. A new technique of closed-chest percutaneous left heart bypass that can be used in patients with acute evolving myocardial infarction and cardiogenic shock is also described. PMID- 3331314 TI - Percutaneous cardiopulmonary bypass and innovations in clinical counterpulsation. AB - This report points out the progress that has been made with cardiac support devices since they were first clinically applied in the mid-1960s. Advances in technology have allowed the development of PBY. Innovatively applied modifications of existing support systems have allowed patient survival when conventional systems could not be utilized. Continued refinements in design, materials, and power sources will allow circulatory assistance to progress as an extremely useful clinical tool for the treatment of patients with acute and chronic ventricular failure. PMID- 3331313 TI - Current status of external counterpulsation. AB - This article traces the development of external counterpulsation from its beginnings to the present. Initially, counterpulsation was carried out by cannulating the femoral artery. The hemodynamic goals were to reduce the afterload of the left ventricle, and to raise or augment the diastolic pressure. This gave rise to the term "counterpulsation." The intra-aortic balloon is capable of producing these salutary effects because of its proximity to the outlet of the left ventricle. The same hemodynamic effects can be obtained by external counterpulsation. However, one must produce a negative pressure during cardiac systole, and ensure that this is applied to the lower extremities. The only clinical study in which this was done was in the treatment of patients in cardiogenic shock by Soroff and colleagues. The results of the clinical studies reviewed are all suggestive of benefits derived from external counterpulsation in a variety of clinical settings. These studies suggest the following avenues for improvement in the equipment used to carry out external counterpulsation: 1. Inclusion of the vascular bed of the buttocks to be subjected to the external pressures, as advocated by Zheng. 2. Inclusion of a negative pressure blanket, as advocated by Soroff. 3. Further investigation of graded-sequential external counterpulsation, using the buttocks and negative pressure. 4. Application of external counterpulsation earlier in cardiogenic shock and for at least 4 hours in acute myocardial infarction. Our evaluation is that this method has not been studied in a way that demonstrates its full potential. We feel that it is on the threshold of being shown to be useful in all of the clinical settings reviewed, and we hope that the necessary equipment will be created to allow investigators to establish its proper place in our therapeutic armamentarium. PMID- 3331315 TI - Abdominal binding and counterpulsation in cardiopulmonary resuscitation. AB - During the past 15 years, many different studies have documented improved blood pressure and blood flow above the diaphragm when some type of abdominal compression was added to conventional CPR, either in animals or in humans. Rhythmically interposed abdominal compressions seem to provide even greater hemodynamic benefit than continuous abdominal binding. Both total flow and the distribution of flow to vital organs above the diaphragm are improved, while the chances of liver entrapment and damage during chest compression are reduced. The technique of interposed abdominal compression can be performed with the bare hands of a second or third rescuer. It requires no special equipment, and could be easily incorporated into existing training programs for basic rescuers. In this sense the technique may constitute a logical evolution in basic life support, if subsequent clinical research confirms that it improves outcome. PMID- 3331316 TI - Controversies in cardiopulmonary resuscitation. AB - This article reviews cardiopulmonary and cerebral resuscitation. New experimental and clinical information is presented, with some guidance for present therapy and future investigations. PMID- 3331318 TI - Pulmonary embolism: diagnosis and treatment. AB - Pulmonary embolism is a condition with a potentially high mortality that often goes unrecognized. Prompt diagnosis and treatment effectively reduce the mortality rate. Clinical judgment alone is insufficient for diagnosis; objective testing is needed. Once the diagnosis is made, effective treatment should be instituted. Treatments differ, based on several factors including disease severity, contraindications to treatment and pre-existing diseases. The major thrust of training should be to teach medical care workers how to prevent deep vein thrombosis and its most serious complication, pulmonary embolism. PMID- 3331317 TI - Infective endocarditis: a pathophysiologic approach to therapy. AB - The treatment of infective endocarditis requires a multidisciplinary approach, including the expertise of cardiologists, infectious disease specialists, and cardiothoracic surgeons. By drawing from the pathophysiology, this article discusses a multidimensional approach to the treatment of these difficult patients. PMID- 3331319 TI - Anticoagulation in patients with valvular heart disease, atrial fibrillation, or both. AB - Despite the availability of anticoagulant drugs for many years, there are still controversies regarding their use in many cardiovascular conditions. In this article, the pharmacology of warfarin and heparin are reviewed, and the clinical applications of these therapies in patients with valvular heart disease, atrial fibrillation, or both, discussed. PMID- 3331320 TI - Renal considerations in cardiovascular drug therapy. AB - The increasing number of patients with both cardiac and renal disease makes it important for the clinician to bear in mind the effect of both renal failure and peritoneal or hemodialysis on the handling of drugs. Guidelines are available for specific medications; however, they must be used in the light of the patient's individual response and metabolism. PMID- 3331322 TI - The anatomy of the foot. PMID- 3331321 TI - Innovative drug delivery systems in cardiovascular medicine: nifedipine-GITS and clonidine-TTS. AB - Innovative drug delivery systems have been developed for nifedipine and clonidine that prolong the pharmacologic activity of the medications, allowing once daily dosing. The nifedipine-GITS (gastrointestinal therapeutic system) tablet formulation and the clonidine-TTS (transcutaneous delivery system) patch may also reduce side effects in patients while preserving the therapeutic efficacy of the origin drug formulations (nifedipie capsule, clonidine tablet). PMID- 3331323 TI - Biomechanical analysis of foot structure and function. PMID- 3331324 TI - Seronegative arthropathies in the foot. AB - It has been seen that involvement of the foot in the seronegative arthropathies forms a regular and varied part of the clinical picture. This is often quite different from that seen in rheumatoid arthritis; its components, whether in joints, periarticular structures, or as surface manifestations, may be characteristic enough to raise the diagnosis of 'spondarthritis'. The features described, though characteristic of the spondarthritides, are, however, not pathognomonic. Thus, the osteolysis in psoriatic arthritis also occurs in neuropathic arthritis (e.g. syringomyelia, leprosy), psoriatic periosteal changes may mimic osteosarcomatous proliferations, and the calcaneal enthesitis so typical of spondylitis, Reiter's disease and psoriatic arthritis, may also be seen in metabolic arthropathies. It should also be mentioned here that the severe erosive osteolytic changes leading to psoriatic arthritis mutilans may also be seen, albeit rarely, in rheumatoid arthritis. Ankylosis, too, is not totally confined to the spondarthritides, having also been reported in occasional patients with rheumatoid arthritis. Calcaneal erosions, sometimes envisaged as a spondarthritic feature, also occur in rheumatoid patients. Within the spondarthritis matrix, a striking overlap is seen in the pattern of arthritis. Thus, involvement of the feet in psoriatic arthritis and in Reiter's disease shows many similarities, particularly the tendency to involve IP joints in asymmetrical oligoarticular fashion. In the hindfoot, too, parallels can be drawn between the tendency to Achilles and plantar insertion enthesitis in ankylosing spondylitis and Reiter's disease. On the other hand, the arthropathies of the chronic inflammatory bowel diseases, ulcerative colitis, Crohn's disease, and Whipple's disease, share with Behcet's syndrome an asymmetrical involvement of knees and ankles, but relative freedom from foot involvement. Regarding the surface features in the foot of spondarthritides, there is overlap here, too. For example, the nail dystrophy of psoriasis can be indistinguishable from that of Reiter's disease, and pustular psoriasis in its severe form cannot be differentiated from keratoderma blenorrhagica, even at the histological level. Other surface manifestations affecting the lower limb in general distribution may spread to the feet and thus fall within the ambit of this discussion. Such features include the lesions of erythema nodosum, patches of pyoderma gangrenosum, and the tender cords of thrombophlebitis, all of which have a higher prevalence in seronegative arthritis than in seropositive disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3331325 TI - Vasculitis and ulceration in rheumatic diseases of the foot. PMID- 3331326 TI - Skin and nail changes in the arthritic foot. AB - The arthritic process is unlikely to be confined to the foot; similarly the cutaneous lesions associated with the arthritic foot are often widespread. Careful examination of the skin and nails, particularly the finger nails, may be helpful in the differential diagnosis when the patient presents with a painful foot joint. Conversely, certain cutaneous lesions may alert the physician to the possibility of joint disorders presenting at some later date. In this chapter, it is not possible to mention every skin lesion associated with an arthropathy. Some skin lesions are specific but many are non-specific and occur in several rheumatic diseases. The rheumatologist and dermatologist work in closest co operation when managing patients with lupus erythematosus and psoriatic arthritis and it is for this reason there is particular emphasis on these two diseases. Patients with rheumatoid arthritis and gout usually come within the province of the rheumatologist, but there are often many characteristic dermatological features to these diseases. This chapter also includes some more esoteric diseases such as Familial Mediterranean fever, Behcet's syndrome, disseminated gonococcal infection and Lyme disease which may present a diagnostic problem to the general physician, rheumatologist or dermatologist. PMID- 3331327 TI - Surgery and the forefoot. PMID- 3331329 TI - Epidemiological aspects of rheumatic diseases and their relevance to clinicians. PMID- 3331330 TI - Sociological aspects of rheumatic patients. PMID- 3331328 TI - The history of shoes. PMID- 3331331 TI - Epidemiological, sociological and environmental aspects of rheumatoid arthritis and osteoarthrosis. PMID- 3331333 TI - Gout. PMID- 3331332 TI - Seronegative spondarthritides. AB - We have attempted to review the epidemiology of a group of diseases collectively termed the seronegative spondarthritides. In discussing environmental influences on these diseases we have reviewed shared aetiological hypotheses and how these have been, and may be, manipulated to influence disease development. The socioeconomic impact of disease has been discussed, together with some of the strategies we might adopt to prevent further disability and handicap. Recent developments, particularly in the laboratory, promise imminent advances in the aetiopathogenesis of this group of chronic inflammatory disorders. PMID- 3331334 TI - Scapulohumeral syndromes. PMID- 3331335 TI - Rheumatic diseases: a general practitioner's view. AB - Patients with rheumatic complaints are the subject of some 10% of the general practitioner's work. Approximately half of this work is related to the hitherto relatively neglected group of varied soft-tissue conditions, most of which are self-limiting and of a minor nature. Against a background of such diagnostic 'noise', the general practitioner has to remain alert for the fainter 'signal' of serious disease--rheumatic and non-rheumatic--at an early stage. Continuity of care calls on special qualities, behaviours and abilities in the doctor to boost and maintain morale, to coordinate management and to participate in team care. In addition to more traditional therapeutic measures, including analgesics, NSAIDs, disease-modifying drugs and physiotherapy, joint replacement is seen as a significant contribution. There is room for improvement in the structure process and outcomes of delivery of care as it may relate to rheumatic diseases. A simple illustration, based on a general practice audit of gout, is suggested as a possible model by which quality of care could be enhanced at the level of individual patients. While there is not a great deal of scope afforded to the general practitioner in the exercise of primary prevention of the rheumatic diseases, early diagnosis and timely support for carers of patients suffering from chronic rheumatic diseases are areas worth attention. Promotion of self-help is seen as a worthwhile activity in humanitarian and economic terms, though it calls for an appropriate balance to be struck. PMID- 3331337 TI - Conformational changes and dynamics of tRNAs: evidence from hydrolysis patterns. PMID- 3331338 TI - Implications of intermolecularly catalyzed reactions by the Tetrahymena ribozyme. PMID- 3331336 TI - The practising rheumatologist's view. PMID- 3331339 TI - Genetic delineation of functional components of the group I intron in the phage T4 td gene. PMID- 3331340 TI - Group II intron self-splicing: development of alternative reaction conditions and identification of a predicted intermediate. PMID- 3331341 TI - Splicing of messenger RNA precursors. PMID- 3331342 TI - Evolution of the RNA coliphages: the role of secondary structures during RNA replication. PMID- 3331343 TI - Structural studies of Klenow fragment: an enzyme with two active sites. PMID- 3331345 TI - Lactobacillus leichmannii and Escherichia coli ribonucleotide reductases: chemical and structural similarities. PMID- 3331344 TI - The role of protein folding in the evolution of protein sequences. PMID- 3331346 TI - Crystallography and site-directed mutagenesis of yeast triosephosphate isomerase: what can we learn about catalysis from a "simple" enzyme? PMID- 3331347 TI - Evolution of catalysis in the serine proteases. PMID- 3331348 TI - Implications for enzymic catalysis from free-energy reaction coordinate profiles. AB - The constraints on the internal ground and transition states of enzyme-bound intermediates are mandated by the overall free-energy change in the direction of flux (Chin 1983; Stackhouse et al. 1985; Raines 1986) and the barrier for combination with reagent. Within these confines there are many solutions to transit the reaction coordinate. The path taken may reflect the function of the enzyme in question; particularly, whether in addition to catalysis there is a need to optimize reaction accuracy (Cramer and Freist 1987), to perform mechanochemical coupling (Jencks 1980), or to create metabolic control (Newsholme and Crabtree 1981; Koshland 1984). PMID- 3331349 TI - On the evolution of specificity and catalysis in subtilisin. PMID- 3331350 TI - The role of RNA and protein in ribosome function: a review of early reconstitution studies and prospects for future studies. PMID- 3331351 TI - New aspects of structure, assembly, evolution, and function of ribosomes. PMID- 3331352 TI - Evolving ribosome structure and function: rRNA and the translation mechanism. PMID- 3331353 TI - On the modus operandi of the ribosome. PMID- 3331354 TI - Approaches to the determination of the three-dimensional architecture of ribosomal particles. PMID- 3331356 TI - [The Kleinert method in the treatment of injuries of the tendons of the flexor muscles of the fingers]. PMID- 3331355 TI - Role of directional mutation pressure in the evolution of the eubacterial genetic code. PMID- 3331357 TI - [Modification of Lukasik's two-story suture in the treatment of recent injuries of the Achilles tendon]. PMID- 3331360 TI - My life in Nilam. PMID- 3331359 TI - Dr. Alford's hydraulic dental motor. PMID- 3331358 TI - A tour of the ADA's dental artifact collection. PMID- 3331361 TI - Computer-aided design in dentistry. PMID- 3331362 TI - Crevicular leucocytes in periodontal disease. PMID- 3331363 TI - Effect of polishing the fitting surface on retentive efficiency of maxillary complete denture. PMID- 3331364 TI - A universal electrolytic etchant for non-precious crown and bridge alloys. PMID- 3331366 TI - Structure and regulation of glutathione S-transferase genes. PMID- 3331365 TI - Regulation of bacterial metabolism by protein phosphorylation. PMID- 3331367 TI - Enzyme-activated/mechanism-based inhibitors. PMID- 3331368 TI - Polyamines. PMID- 3331369 TI - [Gyno-Trosyd (tioconazole) in the treatment of mycotic vaginitis in women]. PMID- 3331370 TI - [Diagnostic value of a bacterioscopic method used for the evaluation of vaginal biocenosis]. PMID- 3331371 TI - Contemporary insights into the regulation of luteinizing hormone secretion in man. AB - Recent advances in clinical investigative techniques have now permitted the delineation of a spectrum of distinct pathophysiological disorders of gonadotropin secretion in the human, and have suggested important therapeutic avenues for the treatment of clinical hypogonadism in men and women. Advances have occurred in part in the arena of methodology with a broader assessment of the full physiological spectrum of pulsatile gonadotropin secretion, and in part in the use of more refined and selective pharmacological tools to investigate the neuroendocrine facets of gonadotropin dynamics. PMID- 3331372 TI - Nonsteroidal antiestrogens are estrogen-receptor-targeted growth inhibitors that can act in the absence of estrogens. AB - The mechanism of the antiproliferative effect of nonsteroidal antiestrogens (tamoxifen, hydroxytamoxifen) is discussed from studies performed in human breast cancer cell lines. At least two types of mechanism have been evidenced. In the presence of estrogens, antiestrogens behave as classical antihormones and their inhibition of cell proliferation is likely due to inhibition of the synthesis and release of several estrogen-induced mitogens (growth factors and proteases). In the absence of estrogens (cells cultured in phenol-red-free medium), antiestrogens can still inhibit the effect of growth factors (EGF, insulin). At concentrations less than or equal to 4 microM, antiestrogens are also cytotoxic and they require accessible estrogen receptors for their action. 'Estrogen receptor-targeted drugs' is therefore a better general term than 'antiestrogens' to describe the mechanism of action of these drugs, which can also function without inhibiting estrogen action. PMID- 3331373 TI - Antiestrogens, different sites of action than the estrogen receptor? AB - Nonsteroidal antiestrogens display antagonistic as well as agonistic properties when compared with estrogens. These observations and studies of their molecular interactions suggest that part of their activity is mediated through estrogen receptor (ER)-mediated pathways. However, other data, concerning mainly effects on growth and cellular proliferation, cannot be explained on this basis. Recent investigations have shown binding of these molecules to a number of other intracellular binding sites beside ER. Using different cell variants of the human breast cancer cell line MCF-7 we could confirm the peculiar role of one of these sites, the specific antiestrogen-binding site (ABS). Published data on ABS are critically reviewed. PMID- 3331374 TI - Antiestrogen action of progesterone in breast tissue. AB - This review analyzes recent data from international literature concerning the antiestrogen action of progesterone and progestins at the level of mammary cells in culture from either breast cancer lines or normal breast obtained from reduction mammoplasties. Most data indicate that progesterone and progestins have a strong antiestrogen effect on breast cell appreciated by the decrease of estradiol receptor content, the decrease of cell multiplication and the stimulation of 17 beta-hydroxysteroid activity which may be considered as a marker of breast cell differentiation dependent of progesterone receptor. PMID- 3331375 TI - Antiestrogens as treatment of female and male infertilities. AB - Antiestrogens are widely used to treat eugonadal anovulation, luteal phase deficiency (LPD) and oligospermia. This paper reviews the rationales, endocrine effects, profertility effects and side effects of these treatments. Furthermore, we present our own experience of the use of antiestrogens in this field. We have compared the results of clomiphene citrate (CC) to those of tamoxifen (TAM) in a randomized study including 66 infertile women presenting eugonadal anovulation (n = 26) or LPD (n = 40). Both drugs obtained the same pregnancy rate of 80% at 9 months in the anovulatory patients. Conversely, CC was superior to TAM in the LPD cases (pregnancy rates at 6 months of respectively 40 and 11%). The abortion rates were of 11% on CC versus 36% on TAM. Both drugs significantly increased the luteal phase length and plasma progesterone level to the same extent. The results of endometrial biopsies suggest that the difference in their effects on female fertility could result from a detrimental effect of TAM on endometrium. The rates of the side effects proved to be almost identical on both drugs. Thus the use of TAM is not justified as a first-step treatment in ovulation disturbances. TAM should be reserved for patients who experience severe visual side effects on CC. We have also tested TAM in 100 subfertile males. In the 92 oligospermic males, TAM significantly increased the mean sperm count only in the normogonadotropic patients, but as much whether oligospermia was idiopathic or not. Sperm improvement was not significantly related to any hormone criterion except basal serum FSH. The cumulative pregnancy rate was of 41.2% at 1 year. Whether TAM actually improves male fertility, and is superior to CC in this indication, remains to be confirmed in controlled studies. PMID- 3331376 TI - Design of antiandrogens and their mechanisms of action: a case study (anandron). AB - The design of a new drug is conditioned by knowledge of the biochemical mechanisms involved in the etiology of the disease to be treated. With regard to endocrine pathologies, such knowledge can be obtained in the clinic from systematic assays of urinary and plasma hormones, enzyme activities and target tissue receptor concentrations. The present paper describes the results of our assays of plasma 3 alpha-androstanediol glucuronide, 5 alpha-reductase and androgen receptor in prostate cancer patients. The activity of the nonsteroid antiandrogen anandron is discussed in relation to these parameters: anandron may inhibit slightly adrenal androgen biosynthesis but, in particular, counters the action of these adrenal androgens on the prostate. It does not inhibit rat prostate 5 alpha-reductase activity but interacts with androgen receptor to exert an antiandrogen action. PMID- 3331377 TI - Effects of drug administration on gonadotropins, sex steroid hormones and binding proteins in humans. AB - The possible mechanisms by which the administration of drugs may alter the gonadal function in humans are considered in this review. Based on personal data, and on data published in the literature, the following events may occur: (1) blockade of gonadal steroidogenesis; (2) interaction of drug(s) with the steroid binding protein system in plasma, and (3) interference of drug(s) at the level of the feedback control of gonadotropin secretion. Representative examples of the above mechanisms are as following: (1) Ketoconazole possesses inhibitory effects in vitro on cytochrome P-450. When given in adult males, it decreased the plasma concentrations of testosterone (T) and androstenedione and increased 17 alpha hydroxyprogesterone levels, suggesting that this drug acts in vivo on gonadal steroidogenesis by blocking the 17,20-lyase. (2) Danazol is a progestagen with high affinity for sex steroid-binding protein (SBP); when given in high dosages in normal males, it increased rapidly the dialyzable fraction (percent protein unbound or free fraction) of T. This suggests that by interacting with the binding sites of SBP, danazol and/or its metabolites displace the fraction of T bound to SBP. However, in males as well as in females, the long-term administration of danazol decreased also the binding capacity of SBP, and consequently increased the free fraction of sex steroid hormones. (3) Dihydrotestosterone (DHT), the most active androgen in many target cells, given at therapeutic dosages to adult males, resulted in a decrease in plasma concentrations of luteinizing hormone (LH) and T, without any significant change in the percent of free T, even though the affinity of DHT for SBP is higher than that of T. This suggests that the main effect of DHT is to inhibit gonadotropin secretion at the central level. (4) Flutamide, a nonsteroidal antiandrogen, increased both LH and T levels, demonstrating its pure antiandrogenic activity on gonadotropin secretion. The consequence(s) of the effects of such drugs on the production, the metabolic clearance rate and the bioavailability of sex steroid hormones are discussed. PMID- 3331378 TI - Fertility control with RU 486. AB - RU 486 is a synthetic steroid possessing antiprogestin and antiglucocorticoid activities. This paper summarizes the main pharmacological properties of this molecule. It is now under the phase II-III clinical studies in the world for early pregnancy interruption. By itself, the drug shows a 85% complete efficacy provided it is given at the dose of 600 mg (3 X 200 mg) once in pregnancies below or equal to 41 days of amenorrhea. The clinical tolerance of the drug is extremely satisfactory, but metrorrhagia can in some instances be heavy, thus necessitating an adequate medical monitoring. The antiglucogenic activity of the molecule has no clinical relevance. In the future, soma data suggest that adjunction of a synthetic prostaglandin analog could somehow increase the success rate, but further studies are necessary to evaluate the effectiveness of such a combination. PMID- 3331379 TI - Nuclear magnetic resonance imaging in oncology. AB - MRI is synonymous with proton imaging. It provides detailed images of gross anatomy and pathology owing to the excellent soft-tissue contrast, signal void of flowing blood, versatile geometry, and freedom from streak artifacts, as well as other advantages summarized in Table 8-2. In the CNS, MRI has emerged as the most sensitive imaging modality in virtually all pathologies--some reservations remaining concerning acute hemorrhage, focal calcifications, and bone detail. Hence, it should be considered the premier noninvasive examination in the evaluation of the cancer patient with any suspicion of CNS pathology. Economics and availability must, of course, be considered when evaluating MR's role relative to CT. MR clearly provides the best means of excluding pathology, particularly in the posterior fossa, and must be considered after a negative CT examination with persistent clinical suspicions. MRI must also be considered in routine surveillance, if the earliest possible detection of metastasis, demyelination, and other pathologies is to be achieved. MRI should be considered in the evaluation of vertebral metastases, spinal cord compression, and back pain because of its ability to depict CSF, spinal cord, disk, and vertebral body as distinct structures and its sensitivity to marrow disease. In the extremities and pelvis, clearer depiction of soft tissues, vessels, and marrow is a proven advantage. Hence, MRI is indicated in the evaluation of prostate/bladder/rectal carcinoma, uterine/cervical carcinoma, soft tissues/bony sarcomas, and bone metastasis/infarction. In the abdomen, MRI's display of the retroperitoneum and sensitivity to liver lesions indicates its use in the evaluation and staging of renal/adrenal carcinoma, retroperitoneal sarcomas, primary liver tumors, and metastases. Moreover, MRI is also indicated in the evaluation of liver or adrenal masses of uncertain histology owing to a limited specificity of the MR signal for adenoma, carcinoma, and hemangioma. In the chest, MRI's advantages are currently limited owing to the excellent quality of CT images of mediastinum and lung parenchyma and the deleterious effects of respiratory motion. MRI's primary indications in the chest are for the distinction of mediastinal and hilar masses from vessels and aneurysms; evaluation of lumenal patency and superior vena cava syndrome; detection and display of pericardial effusion and the relationship of tumor to the pericardium; and evaluation of internal cardiac anatomy, thrombi, and tumor. Because of rapid technological advances, statements concerning MRI's limitations must be guarded.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3331380 TI - Induction chemotherapy as initial treatment for advanced head and neck cancer: a model for the multidisciplinary treatment of solid tumors. AB - The role of chemotherapy in the management of patients with SCCHN has not been adequately defined. For patients with recurrent or metastatic disease, several single agents can induce significant tumor regression in 20% to 40% of cases and provide palliation for the individual with a symptomatic or life-threatening lesion. However, complete or long-term control of tumor with chemotherapy alone remains poor. In addition, current regimens of combination chemotherapy have not proved superior to single agents in this setting. Thus, the routine use of combination chemotherapy for patients with metastatic or recurrent SCCHN cannot be justified outside an investigational study. New single agents of promise must be sought and more active combinations of chemotherapy devised for the treatment of patients with metastatic or recurrent SCCHN. Strategies for drug development include the investigation of cisplatin analogues, such as iproplatin and carboplatin, the exploitation of potentially synergistic drug schedules, and the administration of chemotherapy by continuous infusion. That the use of continuous infusion drug delivery can enhance antitumor activity and limit toxicity for patients with recurrent or metastatic SCCHN was convincingly demonstrated by Kish and co-workers132 in a randomized trial of cisplatin with either bolus or continous-infusion 5-fluourouracil. The antitumor activity of combination chemotherapy may also be increased by the use of mid-cycle nonmyelosuppressive agents, such as methotrexate with leucovorin rescue, or the administration of alternating cycles of non-cross-resistant regimens of combination chemotherapy. The optimal use of chemotherapy in the multidisciplinary treatment of patients with previously untreated SCCHN must also be clarified. Uncontrolled studies of induction chemotherapy report increasingly positive results. Several regimens of induction combination chemotherapy are now associated with significant tumor regression in 70% to 90% of patients, and complete clinical regression of tumor in 20% to 50%. Of patients with a complete clinical response to induction chemotherapy, a complete pathologic response has been documented in 30% to 70% of patients who undergo surgical resection after chemotherapy. It is now evident that patients achieving a complete response to induction chemotherapy have a high probability of local-regional control of tumor and cure. Conversely, patients not responding to induction chemotherapy fare poorly regardless of subsequent local treatment, and it may be appropriate to defer excessively morbid surgical procedures in this patient populus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3331381 TI - Etiology of colorectal cancer with emphasis on mechanism of action and prevention. PMID- 3331383 TI - PDQ: an innovation in information dissemination linking cancer research and clinical practice. PMID- 3331382 TI - New approaches to brachytherapy. PMID- 3331384 TI - The phenomenon of pleiotropic drug resistance. PMID- 3331385 TI - Nonoperative therapy of biliary obstruction. PMID- 3331386 TI - The emerging role of monoclonal antibodies in the clinical management of epithelial ovarian carcinoma. PMID- 3331387 TI - Neonatal diabetes mellitus: evaluation of pancreatic beta-cell function in two cases. AB - Two cases of neonatal diabetes mellitus, a transient form and a permanent form, are described. Comparing their clinical presentations and courses, we exclude the possibility of an early differential diagnosis based on clinical or laboratory data. We hypothesize that only repeated dynamic evaluations of pancreatic beta cell function could be useful to differentiate the two forms. PMID- 3331388 TI - Nonsurgical management of neonatal multiple brain abscesses due to Proteus mirabilis. AB - A newborn infant with Proteus mirabilis meningitis developed multiple brain abscesses with diameters ranging from 2 to 4 cm. Intravenous antibiotic therapy alone without surgical intervention led to the complete resolution of this complication. The case supports that this may be an acceptable treatment of multiple brain abscesses in neonates. However, the clinical outcome was relatively poor, since a porencephalic cyst, hypodense areas in CT scan, and psychomotor retardation were found at one year of age. PMID- 3331390 TI - Entomological investigations of an outbreak of malaria in Chilacap on South coast of central Java, Indonesia during 1985. PMID- 3331389 TI - Visualization of vascular channels in the mandibular cortex. AB - Several methods to visualize the vascular pattern of the mandibular cortex were tested. The most suitable method for young jaws proved to be one in which the organic material was partially removed to increase access to the vascular channels. The vessels were vacuum infiltrated with an India ink solution, and the jaws were then decalcified and cleared in glycerin. This resulted in completely transparent flexible cortical plates showing a sharp outline of the vascular pattern. The flexibility of the plates also improved the morphological study of the emergence of blood capillaries at the cortical surface in relation to bone remodeling. PMID- 3331391 TI - Prophylactic effect of diethylcarbamazine on Wuchereria bancrofti filariasis. PMID- 3331392 TI - Malaria control in Delhi--past, present and future. PMID- 3331393 TI - Treatment with lingual appliances: the alternative for adult patients. PMID- 3331395 TI - Effect of dexamethasone on nitrogen metabolism in brain-injured patients. AB - A randomized prospective clinical trial was conducted to determine the influence of dexamethasone therapy on nitrogen metabolism in patients with isolated head trauma without any pathologies. One group of 12 patients was not given steroids (groups NS). To the 12 patients of the second group, a dose of 0.36 mg/kg/day of dexamethasone was administered for the first nine days of stay (group S) in hospital. At the beginning of the study, between the two groups, there were no differences in age, sex, Glasgow Coma Scale Score, type of injury. In order to avoid bias, phenytoin, barbiturates and muscle-relaxant drugs were not given and the same caloric and protein intake was prefixed for both groups. The urea excretion, nitrogen output, nitrogen balance and cumulative nitrogen balance were not statistically different in the two groups throughout the period of study. Similar were also weight losses, blood glucose, blood urea nitrogen, albumin and creatinine levels. The outcome, evaluated at 3 months, was also similar. The incidence of sepsis, pulmonary and urinary infections, gastric reflux duration and quantity, was not higher in the steroid group compared with non-steroid treated patients. PMID- 3331394 TI - Recurrent cystic meningiomas. Report of two cases. AB - The Authors report 2 cases of recurrent cystic meningiomas among 22 cases operated on. After a review of the literature, the pathogenesis of the recurrences of these tumors is discussed, concluding that wrong interpretation of neuroradiological examination and/or incomplete extirpation of tumoral capsule are the main factors responsible of recurrences of cystic meningiomas. PMID- 3331396 TI - Spondylocostal dysostosis: report of three patients. PMID- 3331397 TI - Effects of diagnostic ultrasound on sister chromatid exchange frequencies of the amniotic fluid cells of the pregnant women. PMID- 3331398 TI - [Delayed-action nifedipine in the treatment of primary hypertension: its effect on blood pressure and serum lipids and lipoproteins]. PMID- 3331399 TI - [Cordipin in the treatment of primary arterial hypertension]. PMID- 3331400 TI - [Clinical observations of using nifedipine in coronary disease]. PMID- 3331401 TI - [Interaction between digoxin and nifedipine in the pharmacokinetic phase]. PMID- 3331402 TI - [Effect of verapamil on the electrophysiological properties of the atrioventricular node in patients with atrioventricular nodal tachycardia]. PMID- 3331403 TI - [Nifedipine (Cordipin) in the monotherapy of mild and moderate arterial hypertension]. PMID- 3331404 TI - [Verapamil in the treatment of paroxysmal supraventricular arrhythmia]. PMID- 3331405 TI - [Use of nifedipine in patients with Raynaud's phenomenon]. PMID- 3331406 TI - Na+-linked active transport of ascorbate into cultured bovine retinal pigment epithelial cells: heterologous inhibition by glucose. AB - The transport of ascorbate into cultured bovine retinal pigment epithelial (RPE) cells is reported. Primary or subcultured RPE cells were incubated in the presence of 10-500 microM L-[carboxyl-14C]-ascorbate for various periods of time. Accumulation of ascorbate into RPE cells followed a saturable active transport with a Km of 125 microM and a Vmax of 28 pmole/micrograms DNA/min. RPE intracellular water was calculated to be 0.8 pL/cell, and the transported cellular ascorbate concentration was 7.5 +/- 0.8 mM. Replacement of 150 mM NaCl in the incubation media with choline-Cl strongly inhibited (80 +/- 8%) ascorbate uptake into cultured RPE cells. Although the depletion of cellular ATP by 2,4 dinitrophenol and the inhibition of Na+-K+-ATPase by ouabain reduced ascorbate transport into RPE significantly, active transport of ascorbate was not entirely inhibited by these metabolic inhibitors. The ascorbate analogue, D-isoascorbate, competitively inhibited ascorbate transport into cultured RPE with a Ki of 12.5 mM. Cells grown in the presence of 5 to 50 mM alpha-D-glucose in the growth media did not differ in their ability to transport ascorbate. In contrast, the presence of alpha-D-glucose or its nonmetabolizable analogues, 3-0-methyl-glucose, alpha methyl-glucose, and 2-deoxy-glucose, but not L-glucose or beta-D-fructose, in the incubation media inhibited ascorbate transport. myo-Inositol (10 or 20 mM) also inhibited ascorbate transport into RPE cells. The active uptake of ascorbate into cultured RPE cells was primarily coupled to the movement of sodium ion down its electrochemical gradient. A bifunctional, cotransport carrier possessing an ascorbate-binding site and a sodium-binding site may be involved in the ascorbate uptake system. The inhibition of ascorbate uptake by sugars appeared to be heterologous in nature, occurring between two distinct carrier systems, both of which were dependent on the sodium ions. PMID- 3331408 TI - Clinical statistics of the adenomatoid odontogenic tumour in Malaysia (1968 1986). PMID- 3331409 TI - Mechanism of cholesterol gallstone formation. PMID- 3331407 TI - Current trends in the surgical management of coronary artery disease. PMID- 3331411 TI - [1948-1988: On the anniversary of the journal "Medicinski Pregled"]. PMID- 3331412 TI - [Historical significance and importance of the founding of the journal "Medicinski Pregled"]. PMID- 3331410 TI - Proximal migration of the Hakim's valve into a porencephalic cyst. PMID- 3331413 TI - [Kidney transplantation (concept, organization and initial results)]. PMID- 3331414 TI - [Immunologic aspects of kidney transplantation]. PMID- 3331415 TI - [Post-marketing surveillance of drugs: epidemiologic approach]. PMID- 3331416 TI - [A meeting of the founders of the journal "Medicinski Pregled"]. PMID- 3331418 TI - Social transition and adolescent development. PMID- 3331417 TI - Research on adolescents and their families: past and prospect. PMID- 3331419 TI - Gender schemata: individual differences and context effects. PMID- 3331420 TI - Development of gender role knowledge and gender constancy. PMID- 3331421 TI - Television and children's gender schemata. PMID- 3331422 TI - [Tooth reimplantation]. PMID- 3331424 TI - Possible neural substrates for orientation analysis and perception. AB - Recent research into the response properties of extrastriate visual cortical mechanisms has revealed single-cell functional organisation which closely parallels certain global and apparently emergent properties of psychophysical observation. An attempt is made to relate previous data on orientation illusions and aftereffects to these extrastriate mechanisms and new data which cannot be explained adequately by V1 (striate) orientation channels are discussed. Conversely, properties of cells in areas such as V3, V4, MT, and others seem to provide an obvious neural substrate for global interactions. It is suggested that psychological 'explanations' couched in terms of 'hypotheses' or 'cognitive problem solving' lack heuristic value, and that, in contrast, the properties of extrastriate cells can suggest novel experimental psychophysical paradigms which are designed to probe these higher-order global mechanisms more or less selectively. PMID- 3331423 TI - [Molecular adhesion to dentin and enamel]. PMID- 3331426 TI - Fetal subdural hematoma: diagnosis in utero. Case report. AB - A subdural hematoma was diagnosed antepartum in an infant by means of sonography. An elective caesarean section was performed because cephalopelvic disproportion, and later the hematoma was drained with a poor evolution due to basal ganglia and intraventricular hemorrhage. No etiological factor of bleeding was found. This is the third published case of fetal subdural hematoma diagnosed antepartum. PMID- 3331425 TI - On the late invention of the stereoscope. AB - It was not until 1838, when Wheatstone published his account of the stereoscope, that stereoscopic depth perception entered into the body of binocular phenomena. It is argued that the stereoscope was not invented earlier because the phenomenon of stereopsis based on disparity had not been adequately described. This was the case despite the fact that there had been earlier descriptions of tasks that could be performed better with two eyes than with one; the perceptual deficits attendant upon the loss of one eye had been remarked upon; analyses of the projections to each eye were commonplace, and binocular disparities were accurately illustrated; moreover, binocular microscopes and telescopes had been made over a century earlier. Theories of binocular vision were generally confined to accounting for singleness of vision with two eyes, and the concepts employed to account for this were visible direction, corresponding retinal points, and union in the brain. The application of these concepts inhibited any consideration of disparities, other than for yielding diplopia. When perception of the third dimension was addressed by Berkeley at the beginning of the eighteenth century, it was in the context of monocular vision and binocular convergence. Thereafter visual direction became the province for binocular vision and it was analysed in terms of geometrical optics, whereas visual distance was examined in the context of learned associations between vision and touch. This artificial division was challenged initially with respect to visual direction and later with respect to stereopsis. An additional factor delaying the invention of the stereoscope was that experiments on binocular vision generally involved abnormal convergence on extended objects. Wheatstone's accidental observation of stereopsis was under artificial conditions in which disparity alone defined the binocular depth perceived. Once invented the stereoscope was enthusiastically embraced by students of vision. It is suggested that the ease with which retinal disparity could be manipulated in stereopairs has led to an exaggeration of its importance in space perception. "The appearances, which are by this simple instrument rendered so obvious, may be easily inferred from the established laws of perspective; for the same object in relief is, when viewed by a different eye, seen from the two points of sight at a distance from each other equal to the line joining the two eyes. Yet they seem to have escaped the attention of every philosopher and artist who has treated of the subjects of vision and perspective." (Wheatstone 1838, page 371). PMID- 3331427 TI - Insidious hydrocephalus in the preterm newborn following discharge from the nursery. AB - Posthemorrhagic ventriculomegaly may be due to perinatal brain damage and consequent cerebral atrophy, or represent progressive hydrocephalus due to impairment of CSF flow and reabsorption. 'Arrested' hydrocephalus occurs when the CSF pathways are adequate and, hence, intracranial hypertension no longer exists. The differential diagnosis is often difficult and insidious progressive hydrocephalus should always be a concern in the high-risk preterm newborn. We report 10 preterm infants who were discharged with the diagnosis of arrested hydrocephalus (7) or cerebral atrophy (3), and who later developed progressive severe hydrocephalus 1.5-15 months after the discharge. Five had been treated with intermittent lumbar punctures, while 4 had not received any treatment prior to nursery discharge. One infant died prior to the shunt procedure. Progressive insidious hydrocephalus should be suspected in preterm infants with intracranial hemorrhage following discharge from the nursery. PMID- 3331428 TI - Malignant supratentorial gliomas in childhood. AB - In this review, we try to review concisely the incidence, genetic predilections, classification, and diagnosis of supratentorial gliomas (astrocytomas, oligodendrogliomas, and mixed gliomas) in children. While surgery and irradiation present the most commonly used and valuable modes of treatment, chemotherapy is a valuable adjunctive therapy. Used either with surgery and radiation in primary untreated patients or at recurrence (progression), chemotherapy can increase useful life. The late effects of treatment are primarily endocrine deficiencies and intellectual impairment; nevertheless, they are not of a degree to preclude aggressive therapy. In order to improve therapy, and because of the small number of patients with supratentorial tumors, collaborative multi-institutional trials should be encouraged. PMID- 3331430 TI - Trigeminal schwannomas in adolescence. AB - Trigeminal neurinomas, unlike those of the acoustic nerve or of other cranial nerves, are relatively frequent in adolescence, making up 10% of the total. Two cases are described, bringing the number of reports in the world literature up to 13. The clinical, radiological and surgical data on these tumors are analyzed, and some particular aspects present in adolescence are pointed out. PMID- 3331429 TI - Neuroplasticity and the developing brain: implications for therapy. AB - Normal brain development consists of a series of interdependent and temporally overlapping processes. These include cell division, migration and aggregation, dendritic elaboration, axonal elongation and arborization, and synaptogenesis. There is a general pattern in all of these of predictable early development with evidence of specificity, followed by a period of remodeling. Lesions of the central nervous system occurring during development will affect these developmental processes at different points in the sequence and therefore have disparate effects on different portions of the brain at any given time of occurrence, as well as different effects depending on the time when the insult occurs. Unlike lesions occurring in the more steady-state condition of the adult nervous system, lesions during development have additional effects in redirecting subsequent development. It is arguable that this implies enhanced opportunities to mitigate the deleterious effects of such lesions. Potential therapeutic interventions can be divided by whether they are applied acutely, subacutely or late after injury. There are reasons for optimism regarding development of powerful new treatments in each of these categories. Further delineation of plasticity and the application of the resulting insights promise exciting and therapeutically important advances. PMID- 3331431 TI - New immunizations for children. PMID- 3331432 TI - Legg-Calve-Perthes disease. PMID- 3331433 TI - Mixed connective tissue disease in childhood. PMID- 3331435 TI - Understanding allergic rhinitis: differential diagnosis and management. PMID- 3331434 TI - Allergy to cow milk--1985. PMID- 3331436 TI - Bronchiolitis. PMID- 3331437 TI - Severe croup: the child with fever and upper airway obstruction. PMID- 3331438 TI - Pulmonary function testing: a practical guide to its use in pediatric practice. PMID- 3331439 TI - The wheezing infant. PMID- 3331440 TI - Prevention and management of infectious diseases in day care. PMID- 3331441 TI - Phenylketonuria--1986. PMID- 3331442 TI - Cystic fibrosis: recent developments in diagnosis and treatment. PMID- 3331443 TI - [Stomatology and dental science in prehispanic Mexico]. PMID- 3331444 TI - [Metronidazole in the treatment of periodontal disease]. PMID- 3331445 TI - [Bar attachments in restorative dentistry]. PMID- 3331446 TI - [The secretory IgA system]. PMID- 3331448 TI - [Immunologic factors in the etiopathogenesis of periapical granulomas]. PMID- 3331447 TI - [Effects of diabetes mellitus on the periodontium]. PMID- 3331449 TI - [Circumpalatal fixation as an adhesion method for skin grafts in the mouth. Report of a case]. PMID- 3331450 TI - [A century of local anesthesia]. PMID- 3331451 TI - [Orthodontics]. PMID- 3331452 TI - Cellular mechanism of the relationship between myocardial force and frequency of contractions. PMID- 3331454 TI - [In memoriam to the most illustrious Dr. Juan Carol Montfort]. PMID- 3331455 TI - [Pearled retainers compared with Maryland retainers in bonded bridges: presentation of two cases]. PMID- 3331453 TI - [Early periodontitis. Review]. PMID- 3331457 TI - [Stomatology in the work of Celsus]. PMID- 3331456 TI - [Saint Apollonia and her iconography (VII)]. PMID- 3331458 TI - [Fit of supporting areas and complete denture equilibration. Apropos of a clinical case]. PMID- 3331459 TI - [Evaluation of the patient with facial pain]. PMID- 3331460 TI - [Nogues. 3 generations of dentists in SS.MM. and Real Casa. Conclusion with delightful anecdotes of dentistry in the land of La Mancha]. PMID- 3331461 TI - [Neonatal systemic candidiasis]. PMID- 3331462 TI - [Prenatal ultrasonographic diagnosis and surgery of urologic abnormalities in newborn infants]. PMID- 3331463 TI - [Severe infections caused by beta hemolytic Streptococcus group A]. PMID- 3331465 TI - [Notes on the history of dentistry in the modern and middle ages]. PMID- 3331464 TI - [Nesidioblastosis with persistent neonatal hypoglycemia]. PMID- 3331466 TI - [The art of dentistry in prehispanic Mexico]. PMID- 3331469 TI - [Some reflections on normality and esthetics in dental prosthesis]. PMID- 3331467 TI - [Study of marginal leakage in the gingival floor of proximal cavities in composite resin restorations]. PMID- 3331468 TI - [The need for individualized cores in fixed prosthesis. Technics]. PMID- 3331470 TI - [Study of acid etching of fissures using scanning electron microscopy]. PMID- 3331471 TI - Renal excretion of drugs and other xenobiotics. PMID- 3331472 TI - Renal and renin effects of sodium thiopental in rabbits. AB - Unilateral renal arterial infusion of sodium thiopental on renal function and renin secretion were investigated in unanesthetized rabbits. Sodium thiopental infusion in doses of less than 0.3 mg/kg/min into unilateral renal artery caused dose-dependent increases in urine flow, urinary excretion of electrolytes, fractional excretion of sodium and free water clearance with no changes in systemic blood pressure and clearance of p-aminohippuric acid (renal blood flow). An anesthetic dose of sodium thiopental administered intravenously caused decreases in systemic blood pressure, renal hemodynamics, urine flow and free water clearance during the early period of anesthesia followed by increases in urinary excretion of sodium and fractional excretion of sodium. Unilateral renal arterial infusion of sodium thiopental decreased the renin secretion rate and plasma norepinephrine concentration in renal vein, whereas an anesthetic dose of sodium thiopental administered intravenously increased the renin secretion rate. These observations suggest that the diuretic, natriuretic and renin suppressive effects of sodium thiopental may be due to an inhibition of intrarenal sympathetic nervous system or due to a direct tubular action. PMID- 3331473 TI - Intranephron distribution of epidermal growth factor immunoreactivity in the mouse. AB - Using a specific and sensitive epidermal growth factor (EGF) radioimmunoassay, the distribution of EGF in mouse kidneys was studied. In five portions (outer cortex, inner cortex, outer medulla I, II, and papilla) of kidney slices, the outer medulla revealed the highest immunoreactive EGF (iEGF) per wet weight of tissue. In microdissected nephron segments, the predominant iEGF per millimeter length was observed in the medullary and cortical thick ascending limbs of Henle's loop compared with other segments. It became more apparent when expressed per milligram protein. Fluorescence microscopy showed prominent staining for EGF in the thick ascending limbs of Henle's loop. The significance of the nephron heterogeneity in EGF contents is discussed. PMID- 3331474 TI - Effects of PGE2 infusion on renal function in normal man before and after angiotensin II inhibition by captopril. AB - Increasing doses of prostaglandin E2 (PGE2) (5, 10, 20, 40, 60 ng/kg/min) were infused in 7 normal volunteers before and after angiotensin II synthesis inhibition by captopril (100 mg by mouth). PGE2 infusion alone did not alter blood pressure, while it increased the urinary excretion of both epinephrine and norepinephrine, enhanced p-aminohyppuric clearance (CPAH), inulin clearance (CIn), sodium and water excretion and decreased urinary osmolality. No changes of CIn, CPAH and catecholamines were observed after captopril alone, whilst there was a significant increase in urine output and sodium excretion and a decrease in urinary osmolality. In the presence of captopril, the infusion of PGE2 caused a significant fall in blood pressure and CIn, enhanced epinephrine excretion and sodium excretion, while it did not significantly reduce CPAH. Our findings suggest that an intact renin-angiotensin system is necessary to maintain GFR during PGE2 infusion. PMID- 3331475 TI - [Legislation on hypnosis (Continuation)]. PMID- 3331476 TI - [The history of Coimbra stomatology]. PMID- 3331478 TI - [Dr. Ferreira da Costa, knight of stomatology]. PMID- 3331477 TI - [Jose de Paiva Boleo: the doctor and the man]. PMID- 3331479 TI - [Moises Gonsalves, pioneer of orthodontics in Portugal]. PMID- 3331480 TI - [Remarks in honor of Sr. Dr. Armando Pena]. PMID- 3331481 TI - [Radiographic evaluation of chromium cobalt castings]. PMID- 3331482 TI - [Rubella in the gestational-puerperal cycle]. PMID- 3331483 TI - [Intrathecal serotherapy in tetanus. Review]. PMID- 3331484 TI - Tuberculosis in renal transplant patients. PMID- 3331486 TI - [Respiratory manifestations in Plasmodium falciparum and vivax malaria]. PMID- 3331485 TI - [Standardization and evaluation of an immunoenzyme assay for the diagnosis and seroepidemiology of human trichinosis]. PMID- 3331487 TI - [In vitro studies of the levels of resistance of Plasmodium falciparum to drugs from 1983 to 1986]. PMID- 3331488 TI - Lectins for the detection of IgM antibodies to T. gondii in the diagnosis of acute toxoplasmosis by immunofluorescence test. PMID- 3331489 TI - [Comparative study of serological tests in the immunological diagnosis of neurocysticercosis]. PMID- 3331491 TI - [History of 2 important zoonoses. Trichinosis and "lepra" (porcine cysticercosis). II. Swine "lepra" with or without porcine cysticercosis]. PMID- 3331490 TI - [Malaria in the municipality of Humaita, State of Amazonas. XXI. Prevalence of glucose-6-phosphate dehydrogenase in a population sample and in patients with Plasmodium falciparum malaria]. PMID- 3331492 TI - [Sero-epidemiologic study of post-vaccination anti-tetanus immunity in Barrado (Caceres)]. PMID- 3331493 TI - [Photoelastic study of fixed prosthetic reconstruction]. PMID- 3331494 TI - [Development of periodontal therapy from the beginning of the century to today]. PMID- 3331495 TI - [Histopathologic changes in the dental pulp in diabetic patients]. PMID- 3331497 TI - [Detection of in vitro-bound complement components on vascular endothelial cells]. PMID- 3331496 TI - [The clinical significance of antibodies to vimentin intermediate filaments in patients with rheumatoid arthritis]. PMID- 3331498 TI - [Collagen arthritis: mechanism and recent advances]. PMID- 3331499 TI - Epidemiological studies on giardiasis in Poznan Province. A review. PMID- 3331500 TI - Genetic and environmental control of blood pressure in twins and their family members. AB - An interdisciplinary study, in adult twins and their family members, of the genetic and environmental determinants of complex physiologic functions is in progress. This report summarizes our initial studies of the control of the level of systolic (K1) and diastolic (K5) blood pressure in 202 monogygotic (MZ) and 121 dizygotic (DZ) twins, their spouses and their children. Correlation coefficients for blood pressure were adjusted for the covariates age, sex, body mass index (wt/ht2) and screener, all of which significantly augment most correlations. These adjusted correlation coefficients in MZ twins are 0.5 for both K1 and K5 blood pressure. For DZ twins, the adjusted correlation coefficients are 0.21 (K1) and 0.24 (K5). MZ twin-offspring adjusted correlation coefficients are higher than MZ twin-niece/nephew adjusted correlation coefficients (0.12 and 0.06, respectively, for K1; 0.20 and 0.13, respectively, for K5), despite the genetic identity of these relationships. That environmental factors may explain these differences is suggested by other differences in adjusted correlation coefficients that are greater than those predicted by the degree of genetic similarity. In addition, we have assessed the relationship between two biochemical-physiological processes, the urinary excretion of kallikrein and transport of sodium in the erythrocyte (the sodium countertransport and the sodium-potassium-chloride cotransport systems), and blood pressure control, since both have been implicated in the control of blood pressure level. Although we found evidence for substantial genetic control of both phenomena, we were unable to establish any correlation between either function and the level of blood pressure in our normotensive subjects. These data point to the operation of three broad categories of control of level of blood pressure: constitutional factors (age, sex, body mass), genetic factors and environmental factors. The identities of the genetic and environmental factors are unknown at this time. PMID- 3331501 TI - Genetic variance estimates and familial resemblance for body size traits. AB - To study genetic contribution to complex body size traits, the intrafamilial correlation and regression analyses along with twin study method have been used. The data are based on a sample of 45 MZ and 101 DZ twin pairs, their 125 singleton siblings, 104 fathers and 103 mothers in 146 Punjabi families living in Chandigarh, India. Twin study gives no evidence of inequality of means and variances between zygosities. Within-pair genetic variance ratios, correlations, regressions of offspring on midparent and single parent are all significant at 0.1%, thus indicating strong genetic component. Heritability estimates are higher for longitudinal body traits than the breadth dimensions. The resemblance of the children with the parents of either sex is not equal. Higher maternal influence is indicated for a number of body traits. The results on familial correlations do not support the hypothesis of sex-linked inheritance for any of the traits considered in this investigation. These results have been compared with those from other such studies. PMID- 3331502 TI - In utero bladder diversion--problems with patient selection. AB - Based upon the concept that an obstruction-maldevelopment sequence is reversible after diversion, it has been suggested that the fetus with a bladder outlet obstruction is a potential candidate for in utero intervention. We report an infant who had both renal and pulmonary dysplasia at birth despite a technically successful diversion at 22 weeks' gestation. The poor outcome suggests that the organ damage either occurs so early that it precludes corrective surgery, or that the maldevelopment is not the result of obstruction, but rather a primary mesodermal defect. PMID- 3331503 TI - Fetal hydrothorax in the second trimester of pregnancy: successful intra-uterine treatment at 24 weeks gestation. AB - Two cases of fetal hydrothorax were diagnosed during ultrasound examination in asymptomatic women in the second trimester of pregnancy. One recognized at 19 weeks gestation increased in size. Thoracentesis at 24 weeks followed by continuous drainage for 7 days relieved the condition. The other diagnosed at 15 weeks resolved over the next month without interference. Each pregnancy resulted in a normal term infant. Aspiration of fetal hydrothorax should be performed when the condition appears progressive and is not associated with a major structural abnormality. PMID- 3331505 TI - A modified IF-test to demonstrate IgM antibodies to Babesia divergens of cattle. PMID- 3331504 TI - [Transplantation of maternal bone for immediate mandibular reconstruction in a child]. PMID- 3331506 TI - Physicians' management of hypertension: a randomized controlled CME trial. PMID- 3331507 TI - Stalking the wild asparagyrus: learning neuroanatomy using an interactive videodisc system. PMID- 3331508 TI - Teaching fundamental electrocardiography to medical students: computer-assisted learning compared with weekly seminars. PMID- 3331509 TI - Practicing physician access to biomedical knowledge: a national study. PMID- 3331510 TI - Symposium: Studies of physician graduates for the evaluation of medical education programs. PMID- 3331511 TI - Symposium: Substance use and abuse among medical students. PMID- 3331512 TI - Symposium: Patient education: clinical applications in medicine. PMID- 3331513 TI - A controlled trial of strategies to improve delivery of preventive care. PMID- 3331514 TI - [Bone grafts for cleft palate]. PMID- 3331515 TI - The coupling of metabolic to secretory events in pancreatic islets: comparison between insulin release and cytosolic redox state. AB - The cytosolic ratio of free NADH/NAD+ and NADPH/NADP+ was measured in rat pancreatic islets exposed to D-glucose, 2-ketoisocaproate or L-leucine. All nutrients augmented both cytosolic ratios above basal value. There was no parallelism between the magnitude of such changes and the rate of insulin release. It is proposed that the changes in cytosolic redox potential do not represent the essential, or at least sole, determinant of nutrient-induced insulin release. PMID- 3331516 TI - Status of calcium influx in cell cycle of S. cerevisiae. AB - The transport of calcium was assayed in exponentially growing and G1 arrested temperature sensitive cdc mutants of Saccharomyces cerevisiae. There was no statistically significant difference in the rate of Ca2+ influx in cdc 28, cdc 37 and cdc 4 arrested cells, as well as in wild type cells arrested in G1 phase in comparison to exponentially growing cells. There was however a significant increase in Ca2+ uptake in cdc 7 and cdc 24 arrested cells. The former is known to arrest before bud emergence and initiation of DNA synthesis; arrest of the latter affects bud formation while DNA synthesis continues. The results suggest that Ca2+ may have a role in bud formation and growth. PMID- 3331517 TI - Effects of ornithine or arginine administration on serum amino acid levels. AB - In healthy humans after overnight fasting, an oral administration of ornithine induced a new steady state: an accumulation of serum alanine and proline, a decrease in serum valine concentration, transient reductions in serum urea and urinary urea contents, and then an increased urea excretion. On the other hand, an oral administration of arginine resulted in an anabolic state: decreases in serum leucine and isoleucine concentrations, reductions in serum glucose and free fatty acid contents and a rapid increase in serum insulin level. It was assumed that the effect of ornithine administration may be exerted through an activation of hepatic System A transport and that of arginine is an insulin-mediated action. PMID- 3331518 TI - Advances in biomedical sensor technology: a review of the 1985 patent literature. AB - The 1985 patent literature pertaining to biomedical sensor technology is reviewed and an assessment made of the types of devices that are most likely to reach commercialisation. Novel systems that are described comprise electrochemical, optical, thermal and other transducers for monitoring key components of clinical samples. These include blood gases and electrolytes, metabolites, enzymes, proteins, antibodies and antigens. PMID- 3331519 TI - [Need for periodontal treatment in an urban population in Madrid]. PMID- 3331520 TI - [Periodontitis: accelerated evolution]. PMID- 3331521 TI - [Nonsurgical treatment of periodontal disease]. PMID- 3331522 TI - [Historical origin of local anesthesia in dentistry]. PMID- 3331523 TI - [Prevention in periodontology]. PMID- 3331524 TI - [Possible errors in occlusal analysis using the Lauritzen Technic]. PMID- 3331525 TI - ["In vitro" study of dentin adhesion to adhesives made from urethane molecules with free groups of isocyanate]. PMID- 3331526 TI - [Influence of the smear layer on the adhesive force of 2 different types of dentin adhesives]. PMID- 3331527 TI - [New attachment procedures in the treatment of osseous periodontal defects. I. Conventional technics, implantation of biological materials and bone grafts]. PMID- 3331528 TI - [Clinical verification of 200 Maryland bridges]. PMID- 3331529 TI - [Alike but not really equal]. PMID- 3331530 TI - [Rapid expansion of the upper jaw. 1. Diagnosis and indications]. PMID- 3331531 TI - [Rapid palatal expansion of the upper jaw. 2. Therapy and clinical cases]. PMID- 3331532 TI - [Watch out for leverage. A case of Kennedy Class III treated with the Kratochvil Pezzoli method]. PMID- 3331533 TI - [The lower anteriors. Study in function of prosthetic reconstruction]. PMID- 3331534 TI - [Combined technic for post dies]. PMID- 3331535 TI - [The direct Maryland]. PMID- 3331536 TI - [Final modification]. PMID- 3331537 TI - [Exploring the fossa]. PMID- 3331538 TI - [Focus on amalgam cavity. From "modern" to "contemporary" to "conservative": step by step innovations in ideal restoration research]. PMID- 3331539 TI - [Tracing the individualized impression tray]. PMID- 3331540 TI - [Enamel-dentinal adhesives]. PMID- 3331541 TI - [New or recycled brackets?]. PMID- 3331542 TI - [Wear of posterior composites]. PMID- 3331543 TI - [The working impression]. PMID- 3331544 TI - [Value of PMNL counting from gingival sulcus and the amount of gingival liquid in the determination of gingival inflammation degree]. PMID- 3331545 TI - [Comparison of two different types of composite resin systems' retention used for cementing laminated veneers]. PMID- 3331546 TI - [History of periodontology]. PMID- 3331547 TI - [Evaluation of some physical properties of silicone rubber used as denture liner and its effect on the growth of Candida albicans]. PMID- 3331548 TI - [Dimensional differences in stone casts from trays made of different materials]. PMID- 3331549 TI - Pharmacological treatment of head injury--a new challenge. PMID- 3331550 TI - An overview of head injury: its consequences and rehabilitation. AB - This article provides a broad overview of the consequences of head injury and approaches to its rehabilitation. Of necessity, no specific area is covered in depth. Sufficient references are provided, however, for the reader who desires further information in any of the areas discussed. It is hoped that, by providing this broad overview, the reader will develop a generalized picture of head injury rehabilitation. Furthermore, the article is designed for 'novices' in the field of head injury rehabilitation such as (1) the family/significant others of the injured persons--so they may begin to know what to expect and to plan for appropriate services; (2) the rehabilitation student--so he or she may be introduced to this emerging specialization and thereby make more informed career choices; and (3) perhaps most important, the newly hired, novice head injury practitioner. This article could form the nucleus of an orientation or in-service training programme for new employees who are not sufficiently knowledgeable in this specialization. In-service programmes are often a necessity for new employees (even on the graduate level) because of the recent, large increase in the number of facilities and programmes specializing in head injury rehabilitation, and because of the lack of available head injury rehabilitation education and training programmes. PMID- 3331551 TI - [The activation of T-lymphocytes in the central nervous system]. PMID- 3331552 TI - [Physiology and pathophysiology of slow eye movement and stabilization of sight]. PMID- 3331554 TI - Microskin grafting. II. Clinical report. AB - A technique for microskin grafting for treating extensively burned patients is presented. Eight extensively burned patients were treated in this way with encouraging results. The recipient area covered by microskin grafts ranged from 2.5 per cent to 44 per cent of the total body surface area (TBSA). The expansion ratio of the micrografts was 15:1 maximum. The micrografts took well in seven patients with the healing time ranging from 22 to 45 days post-operatively. One case failed because of sloughing of the homograft. The advantages of the microskin grafting are: (1) economical use of autografts, (2) the procedure is simple, (3) there is less scar on the recipient site. This new technique is effective, simple and feasible in extensive burns. PMID- 3331553 TI - Microskin grafting. I. Animal experiments. AB - This article reports a new grafting technique--microskin grafting. These experiments were carried out in rabbits, and used a small amount of autograft minced into tiny pieces and then spread on a piece of homograft. The combined autograft plus homograft was then transplanted onto the wound of a rabbit. In 12 rabbits, the microskin grafts took well and covered the wound completely in 8 rabbits. The expansion ratios of the micrografts were from 7:1 to 15:1. The healing time of the wound was from 19 to 35 days. The operation failed in 4 rabbits because of the homograft moving. Histological sections revealed that microskin grafts orientated upwards can grow well and those orientated in a lateral or downward direction can grow too. This technique is an effective procedure for repairing extensive wounds with smaller donor sites. PMID- 3331555 TI - The clinical entity of adult respiratory distress syndrome. Definition, prediction, and prognosis. AB - This article discusses the clinical entity of the adult respiratory distress syndrome (ARDS), its manifestations, and its natural history. The problems of defining the syndrome and its associated risk factors are delineated. In addition, the article reviews the experimental, retrospective, and prospective studies of ARDS risk factors, as well as the clinical correlations with mortality. PMID- 3331556 TI - Pathology of the adult respiratory distress syndrome. AB - Despite the wide range of insults that can lead to the development of ARDS, a common sequence of pathologic changes can be identified in the lung. These changes can be divided into three phases: the acute, or exudative, phase (up to 6 days), in which hyaline membranes are a characteristic feature; the subacute, or proliferative, phase (4 to 10 days), in which metaplasia of the alveolar lining cells and early evidence of fibrosis are seen; and the chronic phase (8 days and on), when organizing fibrosis is a major finding. Structural changes of chronic pulmonary hypertension are also found in the patients with ARDS of longer duration. The mechanism by which these pulmonary changes occur is unknown. Studies of experimental models of ARDS may offer the best opportunity to elucidate the mechanisms. For example, a single infusion of E. coli endotoxin into sheep mimics the pathophysiologic changes of ARDS, offering a model for study of the initial insult on the lung. In addition, animals exposed to high concentrations of oxygen also show morphologic changes similar to those seen in patients with ARDS. Whether the hyperoxia is responsible for such changes, or whether it potentiates the injury induced by some other insult, is not certain. PMID- 3331557 TI - Pathophysiology of the adult respiratory distress syndrome. What have we learned from human studies? AB - Clinical studies of ARDS have been successful in determining the most common predisposing clinical disorders and the natural history of this syndrome. Sepsis, gastric aspiration, and major trauma are the most frequently associated high-risk factors. Overall mortality is in the range of 60% to 70%, but is even higher if ARDS is associated with sepsis, severe acidemia, or decreased renal function. It is evident that multisystem failure is responsible for death in many patients, as well as secondary pulmonary and extrapulmonary infections. Pathologic studies have provided descriptive information regarding the acute, subacute, and chronic phases of the syndrome, but little insight into the precise pathogenesis of the initial lung injury or the progressive fibrosing alveolitis and lung destruction that develops in some patients. There has been considerable circumstantial evidence from clinical studies implicating the neutrophil as a potentially important mediator of the early changes in lung endothelial and epithelial permeability. However, not all investigators have found the same alterations in neutrophil function in the circulation or in the lavage from the lungs of patients with ARDS. Also, the heterogeneous etiologies of ARDS make it difficult to be sure that there is a final common pathway for acute lung injury in all ARDS patients. In addition, there are a host of mediators, including products of complement activation and arachidonic acid metabolism, that may be important in amplifying the inflammatory response. Also, abnormalities of surfactant production and collagen turnover, as well as impaired host defenses in the lung, may contribute to the progressive respiratory failure that occurs in some ARDS patients, even though the acute, exudative phase of lung injury has resolved. Future human studies may provide useful information about the mechanisms of the acute lung injury through studies of circulating plasma markers, blood elements, and lavage fluids from high-risk patients. On the other hand, samples of cells and mediators from the airspaces with lavage still may not reflect the critical interactions of mediators and cells with the lung endothelium that lead to the protein-rich pulmonary edema that characterizes the first phase of ARDS. Thus, experimental studies must continue to study the details of the early phases of acute lung injury (see article by Flick, page 455). Finally, it is clear that treatment designed to reduce the severity and the incidence of ARDS must be started early, since the syndrome develops so rapidly in high-risk patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3331558 TI - The interaction of infection and the adult respiratory distress syndrome. AB - Infection, particularly that involving the respiratory tract, is commonly seen in the patient with ARDS. It can be either an etiologic factor leading to the syndrome or a complicating factor leading to a high likelihood of mortality. Pneumonia develops in up to 70% of individuals with ARDS, and when present, converts the syndrome to its most severe and mortal form. In addition, when systemic injury coexists with any type of infection, ARDS will develop with an increased frequency. Nosocomial pneumonia results when upper and lower respiratory tract defenses fail and these sites are overwhelmed by bacteria. Colonization of the oropharynx and tracheobronchial tree, both of which are common in critically ill patients, precedes the development of pneumonia. In the patient with ARDS, all levels of host antibacterial defenses may be impaired, thus accounting for the high incidence of both colonization and pneumonia. These impairments result from the acute lung injury itself, coexisting systemic illnesses, therapeutic interventions, and acquired malnutrition. Once pneumonia develops in the course of acute lung injury, diagnosis is exceedingly difficult and potentially inaccurate. With proper application of the protected specimen brush, inserted bronchoscopically, diagnostic accuracy may improve. Therapy must be undertaken early and with agents directed at likely pathogens, particularly P. aeruginosa and other gram-negative bacilli. In the future, preventive efforts against pneumonia may be effective for the ARDS patient. Strategies that may be effective include hyperalimentation, judicious use of all pharmacotherapy, active and passive antibacterial vaccines, airway microenvironment manipulation, and the use of aerosolized antibiotics. PMID- 3331559 TI - Altered metabolic function of the pulmonary microcirculation. Early detection of lung injury and possible functional significance. AB - The normal lung is the site of intense metabolic activity, largely associated with the endothelial cell. Depressed pulmonary metabolic function is seen in a wide variety of experimental animal models of acute lung injury, and is also demonstrated in ARDS patients. The evaluation of lung metabolic activity may prove to be a sensitive probe for the detection of the earliest phases of acute lung injury, as well as a guide to the severity of injury or response to therapy. Depressed lung metabolic function may play a role in the intrapulmonary and/or systemic pathophysiology of ARDS. PMID- 3331560 TI - Clinical measurement of extravascular lung water. AB - The thermal-dye technique for the measurement of ELW is available for clinical and experimental use. This method is safe and can be performed serially in an individual patient. Although it is invasive, it requires only a central venous catheter and an arterial catheter, which are often already in place for routine hemodynamic monitoring and management. The procedure is accurate under a variety of conditions. Two obstacles argue against its routine application. First, the reliability of this approach appears to be seriously compromised when there are areas of edematous lung with poor blood perfusion. This includes aspiration and perhaps other forms of acute lung injury. Second, it remains to be demonstrated how useful routine measurements of ETVL, even if accurate, are in clinical management. However, regardless of the accuracy of the various methods for determination of ELW, the process of their development has significantly enhanced our knowledge of pulmonary edema formation and fluid distribution. We are at a transition point of soon being able to determine ELW easily. Techniques of reducing ELW can now be assessed directly in patients with pulmonary edema. As these therapies are developed and understood, the demand for the measurement of ELW will become a greater part of clinical medicine, and may stimulate further refinement of methods for quantitating lung water. PMID- 3331561 TI - Gas exchange in acute lung injury. AB - The predominant mechanism of abnormal gas exchange in patients with the adult respiratory distress syndrome is intrapulmonary shunting. However, other abnormalities of cardiopulmonary function may modify the degree of hypoxemia that is seen, and must be considered when interpreting the effect of therapy. PMID- 3331562 TI - Acute lung injury. Hemodynamic monitoring with the pulmonary artery catheter. AB - Optimal usage of the pulmonary artery catheter demands careful data gathering and integration of the information it provides. This article examines the physiologic basis that underpins the measurement and interpretation of pulmonary vascular pressure, cardiac output, and mixed-venous oxygen saturation data. PMID- 3331563 TI - Respiratory mechanics in the adult respiratory distress syndrome. AB - Recent methods developed for noninvasive determination of the mechanical properties of the respiratory system have been discussed. These methods have already provided valuable information in patients mechanically ventilated in the ICU setting, and could readily be applied to ARDS. More extensive use of such methods should help to provide a better understanding of the physiologic processes and adaptive mechanisms present in both health and disease. PMID- 3331564 TI - Ventilatory management in acute lung injury. AB - Practical theoretic aspects of the adult respiratory distress syndrome and its application to the patient are presented. Rational utilization of mechanical ventilation and positive end-expiratory pressure in the management of hypoxemia is discussed in detail. PMID- 3331565 TI - Hemodynamic assessment and management of patients with the adult respiratory distress syndrome. AB - In summary, ARDS and the combination of MV and PEEP may have complicated hemodynamic effects in terms of cardiac output and regional blood flow. These effects should be assessed primarily in terms of the adequacy of tissue oxygenation. Hemodynamic management of patients with ARDS should be aimed at improving tissue oxygenation by reducing metabolic needs, and improving both the arterial oxygen content (Table 3) and the cardiac output (Table 4). In most patients, these goals can be realized simultaneously. PMID- 3331566 TI - Therapeutic implications of acute lung injury. AB - Although there are no specific therapies for septic shock or acute lung injury that have proven efficacy in humans, a growing understanding of mechanisms of tissue injury has suggested interventions that may prevent or treat this injury. These therapies range from immunization against the glycopolysaccharide core of endotoxin to cyclooxygenase inhibitors to specific oxygen radical scavengers. Each of these treatments is effective in ameliorating at least one of the pathophysiologic manifestations of acute lung injury, although the effect of these agents in the prevention of the sequelae of fibrosis is unknown. Interaction between several factors and mediators is likely necessary for the development of acute lung injury. It is hoped that with additional knowledge regarding mechanisms of injury gained through basic science and clinical research, we can apply definitive therapy that may salvage patients who now die with sepsis and acute lung injury. PMID- 3331567 TI - Pulmonary sequelae and lung repair in survivors of the adult respiratory distress syndrome. AB - The high in-hospital mortality of ARDS has not diminished over the past 10 years, despite improvements in supportive intensive care. Much of the mortality arises from infections, particularly sepsis and pneumonia, and from organ failure, especially kidney failure. The rapid advances in understanding the interlocking pathophysiologic mechanisms of ARDS have not yet been translated into therapeutic trials of new methods for diminishing the injury or for stimulating normal repair. In part, this is because it is difficult to predict which high-risk patients will develop ARDS and then intervene early in the injury process. Patients in whom the risk for ARDS is extremely high have a very high mortality even without ARDS, thereby making efficacy of an early or prophylactic therapy quite difficult to prove. In spite of severe pathologic abnormalities, including fibrosis, early in the course of ARDS, most survivors return to almost normal pulmonary function. The few cases that have been studied with serial biopsies demonstrate resolution of fibrosis. This amazing recovery poses many fascinating questions about how the lung repairs itself. Given the heterogeneous causes of ARDS and the large number of structural, cellular, and biochemical abnormalities described, one can postulate that any one of numerous factors is important in normal repair. Most promising of these are the degree of basement membrane damage, the control of type II cell proliferation and differentiation, the control of collagen synthesis, the anatomic localization of fibrosis, and the control of collagenase action. These interactions of epithelial and mesenchymal tissues probably recreate the process of lung development in the injured adult lung. At a clinical level, the role of oxygen toxicity remains a significant issue. Oxygen acting as an oxidant may be partially responsible for the small airways disease seen in approximately one quarter to one third of survivors. The mortality data stress the need for better ways of preventing and diagnosing lung infections. Better definition of the clinical factors that put survivors at risk for persistent loss of lung function is also needed, and could define a subgroup in which trials of agents designed to improve repair would be most worthwhile. More information about the long-term pathologic course, though difficult to obtain, would also be very important. Perhaps some registry of ARDS survivors would permit closer follow-up and make available more late autopsy pathology when these people die of other causes. The rapid time course of ARDS provides an ideal testing ground for agents designed to either decrease lung injury or stimulate repair.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3331569 TI - Subependymal pseudocyst:a new sonographic finding of an old pathologic lesion. PMID- 3331568 TI - Application of cyclosporin A in renal transplant recipients. Preliminary report. PMID- 3331570 TI - Ultrasound femur length during normal pregnancy. PMID- 3331571 TI - Inverted papilloma of the nasal cavity and paranasal sinuses: report of three cases and review of the literature. PMID- 3331572 TI - Anti-B lymphocytotoxic antibodies and renal transplant outcome. PMID- 3331573 TI - Production and utilization of monoclonal antibodies. PMID- 3331575 TI - [The clinical and epidemiological study of TMJ disorders]. PMID- 3331574 TI - [The definition and etiology of the temporomandibular joint disorders]. PMID- 3331576 TI - [Nonsurgical treatment of TMJ disorders--functional approach]. PMID- 3331577 TI - Statistical methods in medical diagnosis. AB - A review of statistical methods in medical diagnosis is presented. Research has focused on three distinct tasks: classification of subjects into probable diagnostic categories on the basis of presenting clinical indicators (discriminant analysis), assessment of diagnostic test characteristics, and relation of diagnostic testing to subsequent patient management. Although many sophisticated models have been developed for discriminant analysis, recent empirical comparisons indicate that standard methods such as linear discrimination and logistic regression work very well. More research is needed to overcome practical difficulties that are not accommodated in the conventional assumptions. Research on the assessment of diagnostic tests has been oriented more toward selection biases and practical problems. There is a need to develop generalized models for the problem of differential diagnosis. The relation of testing to subsequent management of the patient is a topic that has only recently been explored. It represents an important task in the cost-effective management of health resources. PMID- 3331579 TI - Knowledge coupling, medical education and patient care. AB - Medical education and the acquisition of professional credentials do not guarantee that medical knowledge (information that is taught, apart from the reality of practice, or gleaned from the literature) will be coupled rigorously to the decision-making process of everyday clinical practice. The limitations of the unaided human mind in a memory-based educational system must be forthrightly acknowledged by those who would be responsible for curriculum reform, so the need for new premises and new tools will be recognized and implemented. Because of their knowledge of the many variables that are unique to them, the patients themselves must be given a much more central role in the process of medical care and medical education. Weaknesses of specialization and credentialing in the present obsolete system are analyzed. The behavior of a well-defined system of education and medical care, and the function of the performers within it, are described. Causes of resistance to curricular reform founded on new premises and use of new tools, such as computers, are considered. New computer tools, as components of a problem-solving decision support system (knowledge couplers, knowledge networks, the coupler editor and documentation system, and the computerized patient record), are described. How these might be incorporated into a new type of medical education curriculum is presented. Finally, new goals, within the context of the new premises being implemented into a new system of education and medical care, are outlined. PMID- 3331578 TI - Artificial intelligence in medical diagnosis: the INTERNIST/CADUCEUS approach. AB - The development of computers has provided a potential tool to assist in the management of the information explosion in medicine. The field of medical diagnosis is intellectually challenging and has attracted the attention of computer scientists interested in building expert systems using artificial intelligence techniques. This paper reviews some of the problems of medical diagnosis and discusses examples of programs representing different approaches to solving these problems. The programs developed in our laboratory, INTERNIST 1/CADUCEUS, are discussed in some detail. PMID- 3331580 TI - Local area networks in an imaging environment. AB - There is great interest at present in incorporating image-management systems popularly referred to as picture archiving and communication systems (PACS) into imaging departments. This paper will describe various aspects of local area networks (LANs) for medical images and will give a definition of terms and classification of devices by describing a possible system which links various digital image sources through a high-speed data link and a common image format, allows for viewing and processing of all images produced within the complex, and eliminates the transport of films. The status of standards governing LAN and particularly PACS systems along with a proposed image exchange format will be given. Prototype systems, particularly a system for nuclear medicine images, will be presented, as well as the prospects for the immediate future in terms of installations started and commercial products available. A survey of the many questions that arise in the development of a PACS for medical images and also a survey of the presently suggested/adopted answers will be given. PMID- 3331581 TI - Ultrasonic visualization of the endometrial cycle. AB - The dynamic morphological aspects of the uterine mucosa during the various phases of the endometrial cycle were examined, by using ultrasonographic methods, in 148 patients having regular menstrual cycles and a biphasic basal body temperature. During the proliferative phase, ultrasonographic examinations permitted a visualization of the mucosa in 33%-45% of the cases, respectively in the initial and in the later part of the phase. During the secretory phase, the endometrium was identifiable in 81.4% (initial part) to 90% of the cases (later part of phase). During the menstrual phase, on the other hand, the median echo of the endometrial cavity could never be clearly identified. PMID- 3331583 TI - An overview: the three-rooted lower first permanent molar and its incidence in the three ethnic groups. PMID- 3331584 TI - [Mechanical properties of the Bios clasps]. PMID- 3331582 TI - Determination of ER in ovarian cancer using monoclonal antibody technology. AB - The Monoclonal Antibody technology has been used in 29 cases of ovarian cancer. The immuno-enzyme-assay detected positive levels of estrogen cytoplasmatic receptor in 51.8% of the cases as well as in the nuclear (51.8%). Moreover, the ER/EIA technique screened positive levels of Total ER (ER/t) in 72.4% versus 65.5% obtained by DCC-method. 24.1% of the cases had negative ER/t levels observed by EIA. The monoclonal antibody anti-ER is a very interesting method for studying hormone-dependent tissue, because it uses an immunological binding to antigenic protein (receptor). PMID- 3331585 TI - [Moisture profiles for dental adhesives]. PMID- 3331586 TI - [Accuracy of fit of cast restorations produced in the phantom courses of the conservative dentistry department]. PMID- 3331587 TI - [Dr. med. dent. Walter Drum]. PMID- 3331588 TI - [Intrusion behavior of bridges supported by implants and natural teeth]. PMID- 3331589 TI - [Effect of recasting non-precious alloys on their corrosion resistance]. PMID- 3331590 TI - [Scanning electron microscope evaluation of the etching effect of various gel type acid etchants on enamel]. PMID- 3331591 TI - [Germ count and determination of germ elimination kinetics in bacteremia following extraction of teeth]. PMID- 3331592 TI - [Abrasivity of pellicle under clinical aspects]. PMID- 3331593 TI - [Is Black still up-to-date--from the cariologist's point of view]. PMID- 3331594 TI - [Is Black still up-to-date--from the periodontist's point of view]. PMID- 3331595 TI - [Is Black still up-to-date--from the materials expert's point of view?]. PMID- 3331596 TI - [Contact times between rotary cutting instruments and tooth during cavity preparation]. PMID- 3331597 TI - [Cavity margin and enamel surface after preparation of occlusal cavities with grinding and finishing instruments]. PMID- 3331598 TI - [Spark erosion for correcting the fit of non-precious alloy cast restorations]. PMID- 3331599 TI - [Signs of corrosion on silver posts in root canals (II)]. PMID- 3331600 TI - [Some clinical and microbiological parameters as predictors of changes in clinical attachment following non-surgical periodontal treatment]. PMID- 3331601 TI - [Influence of different construction procedures on occlusal accuracy of complete dentures]. PMID- 3331603 TI - [Effect of various hormonal factors on the incidence of attempted suicide]. PMID- 3331602 TI - [Studies on the effect of L-tryptophan on insulin secretion by the method of in situ perfusion of the rat pancreas]. PMID- 3331604 TI - Pressure studies in arterial surgery. PMID- 3331605 TI - Is your vitreous really necessary? The role of the vitreous in the eye with particular reference to retinal attachment, detachment and the mode of action of vitreous substitutes. PMID- 3331606 TI - Molecular genetic approaches to the analysis of human ophthalmic disease. AB - In this review of the recent literature, the contribution that the new techniques of molecular genetics has made in the analysis and diagnosis of human ophthalmic conditions is presented and discussed. Among the disorders reviewed are X-linked retinitis pigmentosa, Norrie's disease, gyrate atrophy and retinoblastoma, and there are also sections on crystallins and visual pigments. PMID- 3331607 TI - Conjunctival incisions for trabeculectomy and their relationship to the type of bleb formation--a preliminary study. AB - The bleb which develops following trabeculectomy may be diffuse or cystic in nature. Cystic blebs can be complicated by infection, leakage of aqueous, astigmatism, and problems related to contact lens wear, whereas diffuse blebs are not associated with such problems. We report a preliminary prospective photographic evaluation of bleb formation following each of three types of conjunctival incision: (a) fornix based (b) straight limbus based and (c) curved limbus based. The vascular pattern and morphology of the drainage bleb formed was dependent upon the type of conjunctival incision made. The fornix based flap was found most likely to give rise to a diffuse bleb with a normal vascular pattern. PMID- 3331609 TI - [Syndromes of the 1st and 2nd branchial arch: pathogenesis and therapy. 2]. PMID- 3331611 TI - [Surgical and non-surgical therapy compared]. PMID- 3331608 TI - [Reattachment of fragments in coronal fractures]. PMID- 3331610 TI - [Bonded bridges]. PMID- 3331613 TI - [Silanization using own prescription of chemically based confined bonding system]. PMID- 3331612 TI - [Obturator prostheses. Description of 2 cases]. PMID- 3331615 TI - [New prefabricated attachments in dental prosthetics]. PMID- 3331614 TI - [Wax modelling of fixed partial denture. Build-up of occlusal surfaces and preparation of pontic parts]. PMID- 3331616 TI - [Small restoration. Theoretical bases lead to success]. PMID- 3331618 TI - [2. Biomechanical waxing technic. Occlusal function preparation. First three work steps]. PMID- 3331617 TI - [Clinical testing of Silicoater procedures from viewpoint of 3-year experience]. PMID- 3331619 TI - [Sebond-MKV-System. Innovative metal-resin bond]. PMID- 3331620 TI - [Consequences of procedural changes. Savings without loss of quality]. PMID- 3331621 TI - [New generation of synthetic resins. A challenge for every ceramic worker]. PMID- 3331622 TI - [Individual controllable expansion for a tension free poured casting]. PMID- 3331623 TI - [Graphite-containing or graphite-free? Further development of investment materials]. PMID- 3331624 TI - [Between safety and risk: the propensities and resistance to prevention in the daily behavior of adolescents]. AB - Various levels of awareness and attitudes in 2500 High School students regarding prevention of daily risk were examined before and after a special training program on prevention (promoted by the Clinica del Lavoro della Universita di Pavia). The concept of prevention was examined in four analytical realms, through questionnaire and projective tests: actual notion, cognitive organization of knowledge, emotional level, social approval. The data collected showed that the tendency towards prevention of risk is limited in adolescents: from a cognitive point of view, since the conceptual probability of risk is comprehended with difficulty; emotionally, since risk-producing behavior usually provides gratification at various levels; socially, since adolescent usually views risk producing behavior as associated with a positive social image. The informative training session proved to effectively orient the students towards a more rationally controlled behavior, therefore favoring a more positive attitude towards prevention. PMID- 3331625 TI - [Female alcoholism and household conditions]. AB - Alcoholism in women, above all in housekeepers, tends to destroy both families and society. This kind of alcoholism is frequently based on neurosis and depression. Alcoholism in women is supposed to be caused by: genetic factors, psychological factors and social factors. Therefore these components are linked both to neuroendocrinology of female and the way of life of housekeepers. PMID- 3331626 TI - [Passive smoking: a risk factor in the home environment]. AB - Recent studies of the health effects of air pollution have pointed out the importance of environmental smoke as a pollution source in household. Several studies showed that children or adults living with parents or other adults who smoke have an increased risk of several effects: respiratory illness in children, changes of respiratory function in children and adults, risk of lung cancer and risk of other cancer than lung cancer. A few epidemiological surveys have studied the relationship between passive smoking and lung cancer. The available epidemiological studies (10 case-control studies, and 3 prospective studies) have been identified and the results combined. There was a 35% increase of risk of lung cancer among nonsmokers living with smokers as compared with nonsmokers living with nonsmokers. However, adjustments due to some degree of misclassification of some nonsmokers who may be still exposed to other people's smoke, increased the risk, which was thus estimated as 53%. Furthermore, cancer risk deriving from cumulative household exposures to cigarette smoke was evaluated. Overall cancer risk increased progressively with the number of household members who smoked. These results were observed for both smoking related cancer and other sites cancer. Finally, although some of these results need to be confirmed, recent views believe that sufficient evidence is provided that breathing other people's tobacco smoke cause health impairment and lung cancer. PMID- 3331627 TI - Diagnosis and treatment of normal eating. PMID- 3331628 TI - Familial contributions to the etiology and course of anorexia nervosa and bulimia. PMID- 3331629 TI - Primary prevention of eating disorders. PMID- 3331630 TI - Issues in the assessment and treatment of obesity. PMID- 3331631 TI - Identification of target complaints by computer interview: evaluation of the computerized assessment system for psychotherapy evaluation and research. PMID- 3331632 TI - Behavior therapy and tricyclic medication in the treatment of obsessive compulsive disorder: a quantitative review. PMID- 3331634 TI - Fluoride transport: a pH dependent process. PMID- 3331633 TI - Providing relaxation training to cancer chemotherapy patients: a comparison of three delivery techniques. PMID- 3331635 TI - [Extraction for crowding correction]. PMID- 3331636 TI - [Restoration of fractured incisor by the acid etch resin technique: report of one case]. PMID- 3331637 TI - Furcation involvements. Part II. Prognosis and treatment. PMID- 3331639 TI - [Calcifying odontogenic cysts: a review and analysis of twenty-nine cases]. PMID- 3331638 TI - [A comparison of bond strength between dentin and different dentin adhesive materials]. PMID- 3331640 TI - Current classification of periodontal diseases. PMID- 3331641 TI - Recent research in organization and expression of immunoglobulin V region genes. AB - The first Jacques Monod Conference was held in Roscoff, Brittany on 1-5 June 1987 and dealt with the topic of 'Selection of Lymphocyte Repertoires' (organizers F. W. Alt, Columbia University, New York. P.-A. Cazenave, Institut Pasteur, Paris and A. Coutinho, Institut Pasteur, Paris). Much of the meeting was concerned with the recent developments in immunoglobulin and T-cell receptor V region organization and expression. This review is based on the contributions and discussions on Ig V genes, in particular their organization, rearrangements, allelic exclusion and somatic mutation. (Names without references indicate the conference speaker on that topic.) PMID- 3331642 TI - New HLA class I-like alloantigens expressed on blast cells. AB - New beta 2-microglobulin (beta 2-m)-associated, HLA-linked alloantigens, selectively expressed on phytohaemagglutinin (PHA)-activated lymphocytes, were identified using human alloantisera. Reactivity of the antisera against activated cells correlated with HLA-A2, A10 and A28 specificities. The new alloantigens were undetectable on peripheral blood mononuclear cells, B lymphocytes and platelets using either the lymphocytotoxicity or the absorption techniques, and appeared on lymphocytes upon PHA activation, with time-dependent kinetics. They were found on some, but not all, acute leukaemias of B, T and myeloid origin, being absent from chronic B lymphocytic leukaemias. The presence of the new beta 2-microglobulin-associated allospecificities was not correlated with the quantity of classical class I antigens present, as analysed on different cell types by flow cytometry. Thus, these antigenic determinants appear to be different from the classical HLA class I antigens and could be the human counterpart of the murine Qa system or of the second H-2K gene. PMID- 3331645 TI - CAD/CAM: its effects on the practice of dentistry. PMID- 3331643 TI - Genetic studies of low-abundance human plasma proteins. VII. Heterogeneity of the C1S subcomponent of the first complement component. AB - Charge-based structural variation has been observed in the C1s subcomponent of the first complement component C1 after isoelectric focusing and immunoblotting. One common and two uncommon autosomal co-dominantly expressed alleles, designated C1S*1, C1S*2 and C1S*3, have been recognized at the C1S structural locus. The frequency of these alleles was 0.979, 0.016 and 0.005, respectively, in a U.S. white population. No variation at the C1S locus was observed in a U.S. black sample (n = 95). PMID- 3331644 TI - How I beat the mid-life crisis. PMID- 3331646 TI - Monoclonal antibody therapy of leukemias and lymphomas. PMID- 3331648 TI - Production and characterization of monoclonal antibodies (MoAbs) for the ex vivo purging of the bone marrow in patients with multiple myeloma. PMID- 3331647 TI - An immunotoxin made up with campath 1 and saporin 6: preliminary "in vitro" experience. PMID- 3331649 TI - Transfer factor: perspectives in human and veterinary medicine. PMID- 3331651 TI - Recent advances in cellular aberrations in the acquired immune deficiency syndrome. PMID- 3331650 TI - Clinical trials of transfer factor in malignancy. AB - Results of clinical trials of transfer factor therapy in various malignancies have been variable. In non randomized trials, about 300 patients have been evaluated, and clinical benefit has been reported in about 1/3 of the evaluable patients. Results of randomized studies are similarly varied. In some randomized trials, clinical benefits of increased disease free survival and prolonged survival have been claimed. In other studies, transfer factor has been reported to be of no clinical benefit. In a few studies, results suggest patients receiving transfer factor do not do as well as those receiving placebo, although these are only trends, and do not reach the level of statistical significance. There are a number of variables in the design of transfer factor trials, and review of the studies performed to date does not permit a determination of which, if any, of these variables is related to the therapeutic outcome. A variety of tumor types have been evaluated, and it is not clear which, if any, tumors respond to transfer factor. Similarly, the state of disease and prior and concomitant therapy vary widely in these trials and the impact of these variables is unclear. The source and dose of transfer factor also varies. In some studies, attempts have been made to select donors who might have cellular immune reactivity to the tumor being treated, whereas in other studies normal donors have been used. The rationale for the use of normal donors in that the clinical benefit of transfer factor may be related to the non specific immunopotentiating effects of this agent rather than the specific transfer of cellular immunity. Finally, the methods of preparation of transfer factor vary and the products used in various studies cannot be compared by standard biologic or biochemical tests currently available. This review of the literature regarding the clinical effort of transfer factor in malignancy leads to the conclusion that transfer factor might not be an effective therapy of cancer. If it does have efficacy in certain malignancies, it is unlikely that it will alone have dramatic effects in substantial numbers of patients. Perhaps transfer factor may have a role in tumor therapy as an adjuvant to other forms of therapy and as surgery, irradiation, or chemotherapy. In order for the proper evaluation of transfer factor in reproducible comparative studies, it will be necessary to have a standarized reproducible product which can be assessed by appropriate quality control procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331652 TI - Therapeutic perspectives in human immunodeficiency virus infection. PMID- 3331654 TI - Cross-correlation analysis of neuronal activities. AB - Nerve impulses are generally regarded as spike train and analyzed by use of various kinds of so-called time series analyses. Cross-correlation analysis is used to reveal temporal and/or spatial relationships between more than two spike trains in the neuronal circuit, in which two neurons are synaptically connected or two neurons are independent but receive a common input. Three main characteristics of discharge dependency between two neurons become clear from the cross-correlation histogram: 1) the direction of dependency; 2) the latency of interaction; and 3) the type of functional connections between the neurons. We reviewed the cross-correlation analysis from these points of view: 1) what is cross-correlation analysis; 2) what are primary and secondary effects; 3) what kinds of functional information can be obtained from the shape of the primary effect; 4) how sensitively cross-correlation can detect neuronal interaction; 5) how to express quantitatively the primary effect; 6) what kinds of extension technique are available from cross-correlation; and 7) research trends using cross-correlation analysis. PMID- 3331655 TI - On a survey of plasmid DNA in the clinically isolated Shigella strains in Shanghai area and comparison with those from South East Asia. PMID- 3331656 TI - Ganglioside composition of the nerve growth cones. PMID- 3331653 TI - Thymopentin (TP-5) therapy during lymphadenopathy syndrome (LAS/ARC): preliminary report. AB - Persistent generalized lymphadenopathy during HIV infection is now a well classified syndrome featuring multiple chronic lymph node enlargement frequently associated with further symptoms (diarrhea, nocturnal sweating, loss of weight, fever): it is invariably accompanied by serious alterations of the cell-mediated immunity including lymphopenia, reduced number of helper lymphocytes in circulation, inversion of the helper/suppressor ratio, lower proliferative response in vitro and deficient delayed skin sensitivity tests. Minor opportunistic infections are also more frequent, the most widespread being chronic oral candidiasis. Whenever several of these signs are associated in a single patient, especially if the immunitary deficit is severe, an immunomodulating treatment is indicated to improve the lymphocyte functionality and finally to modify any evolutive tendency. The Authors give the preliminary results of a pilot study carried out on 12 patients with LAS/ARC treated with Thymopentin at a dosage of 50 mg by intra muscular injection on alternate days for cycles of 30 days. Compared with 14 untreated patients, the subjects receiving therapy showed a more stable immunological picture, and improvement in subjective symptoms and a better therapeutic response to minor opportunistic infections. PMID- 3331657 TI - Genetic toxicology of flavonoids: the role of metabolic conditions in the induction of reverse mutation, SOS functions and sister-chromatid exchanges. AB - Glycosides of flavonols such as quercetin, are found in the edible portions of most food vegetables. Flavonols present in plants as glycosides can be freed during fermentation. We have compared the DNA-damaging activity of quercetin, rutin (3-o-rutinoside of quercetin) and a fermented flavonoid-containing beverage, red wine, for different genetic end-points under different metabolic conditions. The genotoxicity of quercetin, rutin and commercial red wine has been studied for the induction of: (i) reverse mutation in the Ames assay; (ii) SOS functions in the SOS Chromotest; (iii) sister-chromatid exchanges (SCEs) in human lymphocytes. While in the Ames assay the mutagenicity of quercetin is enhanced by the presence of rat liver microsomal enzymes (S9) or the respective cytosolic fraction (S100), genotoxicity is reduced when the induction of SOS responses is assessed using the SOS Chromotest. Similarly, the induction of SCEs is lowered when testing in the presence of liver enzymes. Rutin has no activity whatsoever. Detection of activity of red wine in the three assays is not dependent upon hydrolysis by glycosidases and its content of quercetin accounts almost entirely for the levels of genotoxicity detected. The results suggest that the putative genotoxic metabolites of quercetin vary for different genetic end-points considered and that the metabolic fate of flavonoids might partly account for the conflicting data about their genotoxicity in vivo and carcinogenic activity. PMID- 3331658 TI - The Second International Collaborative Study on Comparative Mutagenesis re visited: analysis by multi-variate statistical methods. AB - Computerized data analysis methods were applied to a selected subset of the results generated by the International Program on Chemical Safety Collaborative Study on In Vitro Assays. The rationale of this study was the analysis of test performances and the comparison with the conclusions of a similar analysis previously performed on the results of the First International Study. The multi variate data analysis techniques used in the present work proved to be particularly suitable for looking at the complex field of comparative mutagenesis in a logical and systematic fashion, and generated a clear classification of the assays on the basis of their experimental performances. This classification proved not to be consistent with the traditional categories that group tests according to genetic end-point and phylogenetic position, and afforded classes of assays distinct for their sensitivity and specificity in respect to carcinogens. In particular, two systems (Saccharomyces cerevisiae XV185-14C mutation and Syrian Hamster Embryo cells transformation assays) on the basis of the published results, seemed to show a considerable sensitivity in predicting carcinogenicity, although they do not show high specificity. PMID- 3331659 TI - Detection of somatic mutations in man: evaluation of the microtitre cloning assay for T-lymphocytes. AB - A method of detecting 6-thioguanine-resistant lymphocytes by the cloning of T lymphocytes in microtitre wells is evaluated for its usefulness in population monitoring. Factors shown to affect the cloning efficiency of lymphocytes include the strain and irradiation level of the lymphoblastoid feeder cells and the use of a pre-incubation period in bulk culture without mitogenic stimulus before plating at limiting dilutions. Cord blood samples have markedly lower mutant frequencies than adult blood samples. The adult range was 8.0 X 10(-7) to 1.8 X 10(-5). Seven males and seven females aged between 23 and 47 years were sampled. No effect of sex or age was found. Individual samples which were divided at collection and treated separately did not vary from each other, but repeat samples taken at different times showed up to a 2-fold variation. The application of this method in population monitoring is discussed. PMID- 3331661 TI - DNA ethylations induced by ethylnitrosourea in the wild type, cdc4 and cdc7 strains of Saccharomyces cerevisiae. AB - The experiments reported here have investigated the induction of ethylations to DNA in yeast cells exposed to the chemical mutagen ethylnitrosourea. A similar level of alkylation was seen at the N7 and O6 of guanine and at the N3 of adenine in either log phase cells or in temperature-sensitive cdc4 and cdc7 cells growth arrested at their specific G1 positions. Hence the changes in chromosome structure associated with the above cdc phenotypes do not modify the amount of DNA damage induced by ethylnitrosourea. PMID- 3331660 TI - Relationships between the DNA adducts and the mutations and sister-chromatid exchanges produced in Chinese hamster ovary cells by N-hydroxy-2-aminofluorene, N hydroxy-N'-acetylbenzidine and 1-nitrosopyrene. AB - Chinese hamster ovary cells were exposed to N-hydroxy-2-aminofluorene, N-hydroxy N'-acetylbenzidine and 1-nitrosopyrene, and the resulting DNA adducts, sister chromatid exchanges (SCEs) and mutations at the hypoxanthine-guanine phosphoribosyl transferase locus were quantified. Each agent produced a major DNA adduct substituted through the C8 of deoxyguanosine. When the data from all three agents were combined, both mutation and SCE induction correlated strongly with the concentration of DNA adducts. However, significant differences were found in the relationships between adduct formation and the biological responses produced by the individual agents. While N-hydroxy-N'-acetylbenzidine induced the most mutations per adduct, N-hydroxy-2-aminofluorene caused the greatest number of SCEs per adduct. The data support the involvement of C8-deoxyguanosine adducts in mutation and SCE induction, and indicate that the structure of the group adducted to DNA may be an important factor in determining the magnitude of these biological responses. These findings also suggest that SCE and mutation induction are independent expressions of DNA damage. PMID- 3331662 TI - Induction of micronuclei in peripheral erythrocytes of axolotl larvae following in vivo exposure to mutagenic agents. AB - Previous work from this laboratory demonstrated the presence of micronuclei in erythrocytes from larvae of the urodele amphibian Pleurodeles waltl reared in water containing clastogenic substances. In order to investigate the generality of this finding, larvae from another urodele Ambystoma mexicanum (axolotl) were reared in water containing one of the two following compounds: benzo[a]pyrene (BaP) or ethylmethane sulphonate (EMS). The level of micronucleated erythrocytes on blood smears was compared with control samples from larvae reared in fresh water. The optimum larval stage for this test system was determined. The effects of the indirect mutagen (BaP), and the direct mutagen (EMS) were found to depend on both dose and exposure to the clastogen. Positive results were obtained for BaP after 8 days of treatment at a concentration of 0.025 p.p.m. After 10 days of treatment at a concentration of 0.1 p.p.m. numerous micronuclei were seen (greater than 250%). Positive results were also obtained with EMS after 8 days of treatment at a concentration of 24 p.p.m. At 62 p.p.m., positive results were found after 6 days of treatment, while at 124 p.p.m. positive results were found after only 4 days. The results with both these agents show that the axolotl holds promise as an in vivo test system for the detection of low concentrations of clastogens in an aquatic environment. PMID- 3331664 TI - The prospects for a simplified and internationally harmonized approach to the detection of possible human carcinogens and mutagens. PMID- 3331663 TI - Genotoxic activities of 2-nitronaphthofurans and related molecules. AB - The genotoxic activities of 63, 2-nitronaphthofurans and related molecules were examined using two bacterial short-term tests, the Salmonella mammalian microsome assay test or Mutatest, a mutagenesis assay, and/or the SOS Chromotest, an assay for induction of an SOS function in Escherichia coli. Seven compounds were also investigated in the Chinese hamster ovary cells/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) test, a mammalian gene mutation assay. Our main conclusions are the following: (a) Simple empirical rules relating structure to mutagenic activity in the Mutatest can be derived for some of the compounds. In particular, they account for the extremely high Mutagenic Potency of 7-methoxy 1-methyl-2-nitronaphtho[2,1-b]furan (R7372), approximately 2 X 10(6) mutants/nmol on strain TA100. (b) There is a good quantitative correlation between the Mutagenic Potency in the Salmonella/mammalian microsomes assay and the SOS inducing potency in the SOS Chromotest. This, and previous evidence, suggests strongly that the 2-nitronaphthofurans derivatives are essentially recA and thus probably umuDC-dependent mutagens. (c) Four out of seven compounds tested in the CHO/HGPRT assay gave responses correlated with the bacterial responses. One of them, 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), is among, or is, the strongest mutagen described for mammalian cells. We briefly discuss the practical and theoretical implications of these results. PMID- 3331665 TI - Mutation frequencies from X-rays, ultraviolet light, and methyl methanesulfonate in Chinese hamster ovary cells incubated with 3-aminobenzamide. AB - An inhibitor of polyadenosine diphosphoribose polymerase, 3-aminobenzamide, had no effect on survival or mutagenesis in Chinese hamster ovary cells exposed to X rays or u.v. light. After exposure to methyl methanesulfonate, 3-aminobenzamide increased cell killing and mutagenesis at the 6-thio-guanine-resistance locus, but had no effect on mutagenesis at the ouabain-resistance locus. These results are consistent with the greater role played by polyadenosine diphosphoribose in cells damaged by alkylating agents rather than by radiations. PMID- 3331666 TI - Effects of phenoxyacetic acids on the induction of chromosome aberrations in vitro and in vivo. AB - The effects of phenoxyacetic acid herbicides were investigated on the induction of chromosome aberrations in human peripheral lymphocyte cultures in vitro and in lymphocytes of exposed workers in vivo. Pure 2,4-dichlorophenoxyacetic acid (2,4 D; 0.125, 0.150, 0.200 and 0.350 mM) did not increase the number of aberrations, whereas the commercial 2,4-D formulation (0.125, 0.250, 0.500, 1.000 and 1.250 mM, with respect to phenoxyacetic acid concentration) significantly increased the number of chromosome aberrations in vitro (without exogenous metabolic activation). The phenoxy acid levels in the breathing zone of the workers varied between 0.3 and 0.4 mg/m3, and the concentrations of phenoxyacetic acids in the urine of the workers after exposure varied from 0.000 to 0.055 mmol/l. There were no increases in chromosome aberrations in peripheral lymphocytes of the exposed subjects. PMID- 3331667 TI - Conditions for the optimal use of the L-arabinose-resistance mutagenesis test with Salmonella typhimurium. AB - Different conditions of mutagenesis have been compared in order to optimize the use of the L-arabinose resistance test with Salmonella typhimurium. The mutagenesis protocols compared were the plate-incorporation, the pre-incubation and the liquid tests. Fourteen chemicals were used in the comparison: six direct acting mutagens and eight pre-mutagens. Five concentrations of S9 (3, 7.5, 10, 15 and 33% v/v) were compared in the liquid test with pre-mutagens, and three densities of bacteria (ranging from 10(8) to 10(6) cells) were used in the comparison between the plate-incorporation and the pre-incubation mutagenesis test. In general, the liquid test proved the most sensitive mutagenesis protocol. When carrying out this test in a mass screening of mutagens, we propose to select the L-arabinose-resistant mutants in plates supplemented with 0.5 mg of D glucose, and to express the mutagenic response as the absolute number of induced mutants. The plate-incorporation and the pre-incubation mutagenesis protocols could be considered as alternative procedures in the case of previous negative results with the liquid test. Two recommendations can be finally made in order to avoid false negative results: (a) a large population of bacteria (ranging from 10(8) to 10(7) cells) must be exposed to the mutagens in both the plate incorporation and the pre-incubation mutagenesis tests, and (b) ideally, several S9 concentrations (ranging from 3 to 30% v/v) would be employed for testing in liquid samples of unknown mutagenicity. PMID- 3331668 TI - Genotoxicity and polynuclear aromatic hydrocarbon analysis of environmental tobacco smoke samples from restaurants. AB - Acetone-extracted samples of airborne particulate matter collected in three restaurants were analysed for their content of polynuclear aromatic hydrocarbons (PAH) and related polynuclear aromatic compounds (PAC) as well as for genotoxic activity using the Salmonella/microsome assay (strains TA98 and TA100) and sister chromatid exchange (SCE) induction in Chinese hamster ovary (CHO) cell cultures. The total particulate matter varied considerably in the restaurants, being 1.37 mg/m3 at the highest; in the same restaurant the highest amount of total PAHs (168 ng/m3) was also detected. Altogether, 13-22 individual PACs were identified in the samples, ranging from phenanthrene to benzothionaphthene. All of the six samples caused significant increases both in bacterial revertant and SCE frequencies. In the Salmonella assay, the mutagenic activity detected was primarily with metabolic activation. However, in the CHO cell cultures the induction of SCEs was also seen without an exogenous metabolic activation system. The cytotoxicity of the extracts limited the concentration range tested in the SCE assay. Only a partial correspondence of the total PAH content with the genotoxic activity of the samples was found. The genotoxicity of restaurant air exceeded by one to two orders of magnitude the previously reported activities detected by similar methods in urban outdoor and indoor air samples. PMID- 3331670 TI - The expression of recessive markers in presumptive monosomic colonies derived from Saccharomyces cerevisiae, strain D6. PMID- 3331669 TI - Evaluating batteries of short-term genotoxicity tests. AB - Selecting a battery of short-term genotoxicity tests suitable for screening unknown chemicals for carcinogenicity can be a large combinatorial task because of the great number of short-term tests currently available. Biological criteria, such as requirements for different targets and endpoints, can reduce the number of possible combinations. An independent yet potentially complementary approach which we have developed uses Bayes' theorem to predict carcinogenicity from results (positive or negative) in short-term tests. Batteries can be evaluated by their predictivity, calculated with Bayes' theorem from the sensitivities and specificities of the component tests. Our analyses indicate that tests which contribute most to a battery's predictivity are those which are both sensitive and specific, which we call Class I tests. Because few of the currently available tests are Class I, we have extended our analyses to consider when other types of tests must be substituted for Class I tests, the purpose of a particular test program will influence the choice. In order to obtain the best predictions for all chemicals, a battery should include an equal number of Class II tests (i.e. those that are sensitive but are not specific) and Class III tests (i.e. those that are not sensitive but are specific). However, for the purpose of reducing the number of carcinogens erroneously classified as non-carcinogenic, Class II tests contribute about twice as much to the predictivity of a battery as do Class III tests, and for the purpose of reducing the number of non-carcinogens erroneously classified as carcinogenic, Class II tests contribute about half as much as Class III tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331671 TI - The prospects for a simplified and internationally harmonized approach to the detection of possible human carcinogens and mutagens. PMID- 3331673 TI - The induction of DNA adducts in mammalian cells exposed to 1-nitropyrene and its nitro-reduced derivatives. AB - 1-Nitropyrene, 1-nitrosopyrene and 1-aminopyrene were investigated for their ability to induce covalently bound DNA adducts in calf thymus DNA and Chinese hamster lung fibroblasts. Xanthine oxidase catalysed the induction of one major and one minor DNA adduct in 1-nitropyrene- or 1-nitrosopyrene-treated calf thymus DNA, whilst 1-aminopyrene was inactive. These compounds did not form detectable DNA adducts in the absence of xanthine oxidase. The major DNA adduct produced by 1-nitropyrene and 1-nitrosopyrene in calf thymus DNA co-migrated on h.p.l.c., and the structure was consistent with that previously described by others as N (deoxyguanosin-8-yl)-1-aminopyrene. The compounds were investigated for their ability to form DNA adducts in Chinese hamster lung fibroblasts. 1-Nitropyrene (5.2 pmol/mg DNA/h) and 1-nitrosopyrene (129 pmol/mg DNA/h) formed a single DNA adduct in Chinese hamster lung cells which co-eluted on h.p.l.c. with the C-8 deoxyguanosine adduct isolated from 1-nitropyrene-treated calf thymus DNA. 1 Nitrosopyrene was the most efficient compound investigated for the production of the C-8 guanine adducts. In contrast, 1-aminopyrene (14.7 pmol/mg DNA/h) induced the formation of a DNA adduct which did not co-elute with the C-8 guanine adduct. The data presented here suggest that 1-nitropyrene and 1-aminopyrene are metabolized to reactive intermediates which form different DNA adducts in Chinese hamster lung fibroblasts. PMID- 3331672 TI - Carcinogen/mutagen screening strategies. PMID- 3331674 TI - Establishment of lung fibroblastic cell lines from a non-human primate Tupaia belangeri and their use in a forward gene mutation assay at the hypoxanthine guanine phosphoribosyl transferase locus. AB - The cells obtained from a lung of a new-born male Tupaia belangeri were maintained in mass culture for greater than 400 days. After 55 population doubling levels (100 days in culture), three cell lines were separately established; these lines showed constant growth properties. One line, designated as T-23, was used for a mutation assay. The T-23 cells showed an absolute plating efficiency of 30-50%, and a population doubling time of 18-19 h in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. The cells had a modal chromosome number of 62 (pseudodiploid) with the loss of a chromosome and the gain of an unidentified one. T-23 cells, like human cells, were much more susceptible to ouabain than mouse cells but relatively less susceptible to 8 azaguanine, while, unlike human cells, they were less sensitive to 6-thioguanine (6TG). N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was less, but 4-nitroquinoline 1-oxide (4NQO) was more toxic to T-23 cells than to human or mouse cells. Benzo[a]pyrene-induced toxicity was almost comparable among the cell types. For the mutation assay, we chose 6TG-resistance (100 microM) as a marker. The optimal expression time (8-13 days) and cell density at selection to eliminate metabolic cooperation (2 x 10(4) cells/60-mm dish) were determined. Some of the cells selected with 6TG showed less than 0.4% of the total incorporation of [14C]hypoxanthine into wild-type cells, suggesting the mutants under selection were affected at the hypoxanthine-guanine phosphoribosyl transferase locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331675 TI - Metabolic activation of 2-amino-3-methylimidazo(4,5-f)quinoline by hepatic preparations--contribution of the cytosolic fraction and its significance to strain differences. AB - In accordance with previous studies the bioactivation of 2-amino-3 methylimidazo(4,5-f)quinoline (IQ) to mutagens in the Ames test was preferentially catalysed by the 3-methyl-cholanthrene-induced cytochromes P-448, in contrast to the phenobarbital-induced forms of the cytochrome. The mutagenicity of IQ catalysed by microsomes, in the absence of cytosol, was much lower when compared with that observed with S9 fractions. Cytosol itself could not activate IQ but markedly potentiated the microsome-mediated mutagenicity of the carcinogen. The effect of the cytosol was still evident when microsomal metabolism was terminated, indicating that the cytosol contains enzyme(s) that can further convert the microsome-generated metabolites of IQ to more potent mutagens. The cytosolic enzyme(s) were inducible by pre-treatment of the rats with Aroclor 1254. The higher efficiency of activation of IQ to mutagens by Sprague-Dawley S9 mixes when compared with similar preparations from the Wistar rat could be attributed not only to differences in the rate of microsomal metabolism but also to the higher ability of the Sprague-Dawley cytosolic fraction in further metabolizing the microsome-generated metabolite(s). The present study demonstrates clearly that the mutagenic response of this compound in the Ames test may be profoundly modulated by the cytosolic fraction and its role in the metabolic activation of pre-mutagens merits further investigation. PMID- 3331676 TI - Excretion of mutagens in sweat and faeces of man, and in serum, gastric juice and urine of rats, after oral dosing of niridazole or metronidazole. AB - Frameshift mutagens were isolated and concentrated from sweat and faeces of three healthy volunteers (non-smokers) of whom two received 750 mg metronidazole/person and one received 500 mg niridazole. The sweat samples were collected in a sauna a day before and 8 h after oral uptake of the medicaments. The faecal samples were those expelled 12 h before and after drug uptake. All extracts were tested for mutagenicity in the bacterial microtiter fluctuation test employing Salmonella typhimurium TA1538. No mutagenic activity was found with the samples obtained before the drugs were taken, whereas the samples collected after drug treatments were all mutagenic (P less than 0.05). In an animal experiment, female Wistar rats were used to study the time-course of the excretion of mutagens in serum, urine and gastric juice after uptake of 10-20 mg niridazole by gavage. Significant mutagenic activities (P less than 0.001) were found in serum 10 min after and in gastric juice 12h after treatment with niridazole. Non-significant but detectable mutagenicities were found in urine 12 h after treatment, when S. typhimurium G46 was employed as a test organism. These latter mutagenicities were significant (P less than 0.05) 24 h after treatment, they reached a peak of activity (P less than 0.01) 48 h post-administration and disappeared 12 h thereafter. PMID- 3331677 TI - Evaluation of genotoxic potential of khat (Catha edulis) in Swiss albino mice. AB - Genotoxicity of the methanolic extract of khat (Catha edulis) has been evaluated on the male germ cells using the dominant lethal assay procedure in Swiss albino mice. The extract was administered at a dose of 500 mg/kg orally once daily, for five days. Following this sub-acute dose regimen, the effect of khat was studied during the different stages of spermatogenic cycle on the rate of pregnancy and post-implantation losses. Khat reduced the percent pregnancy rates and increased the mean post-implantation losses in the treated group. The increase was found to be statistically significant in the post-meiotic stages. PMID- 3331679 TI - Absence of genotoxic effects in cells exposed to four ketonucleoside derivatives. AB - The relationship between the structure and genotoxic potential of four new cytostatic compounds--the ketonucleosides KN-35, KN-43, KN-44 and KN-3--was investigated in short-term in vitro assays of hypoxanthine-guanine phosphoribosyl transferase locus mutation in V79 cells, induction of chromosomal aberrations and sister chromatid exchanges on human lymphocytes, induction of chromosomal aberrations and micronuclei in V79 cells, and transformation of Syrian hamster embryo cells. None of the ketonucleosides induced mutagenic effects in any of the assays. Their failure to exhibit significantly genotoxic activity may be ascribed to the probable absence of any reaction between these drugs and the cellular DNA, and indicates that they act by some other mechanism which probably differs from the one observed with alkylating or intercalating antitumoural agents. This suggests that the cytotoxic activity of ketonucleosides cannot be related to genotoxicity. PMID- 3331678 TI - Genotoxicity of the antitumor antibiotic CC-1065. AB - CC-1065, a very potent antitumor antibiotic, is active against several animal tumors, and against human tumors in the cloning assay at doses 50-1000 times lower than other agents such as adriamycin. It binds and alkylates DNA, and inhibits DNA synthesis, suggesting a potential for genotoxicity. Therefore, the genotoxic effects of CC-1065 were tested in several assay systems. CC-1065 was weakly mutagenic in the Ames Salmonella mutation assay (strain TA100) without S9 activation, but lacked mutagenic activity in TA98 with or without activation. CC 1065 was a very potent mutagen in the Salmonella forward mutation assay (induction of 8-azaguanine resistance), increasing the mutation frequency 19-fold over background at 0.1 ng/ml without activation. In mammalian (V79) cells it was a very potent mutagen without activation, increasing the mutation frequency 20 fold over background a 0.5 ng/ml. CC-1065 induced chromosome aberrations in V79 cells at very low (less than 0.1 ng/ml) doses, making this assay the most sensitive. CC-1065 increased the induction of micronuclei in rats 10- to 20-fold over the background at 200 and 400 micrograms/kg, but not at 100 micrograms/kg. CC-1065 failed to cause DNA breaks or DNA--protein cross-links as measured by the DNA damage/alkaline elution assay. PMID- 3331680 TI - Species differences in mutagenicity testing. II. Sister-chromatid exchange and micronucleus induction in rats, mice and Chinese hamsters treated with cyclophosphamide. AB - Comparative investigations of sister-chromatid exchange (SCE) and micronucleus induction in the bone marrow of rats, mice and Chinese hamsters with the cytostatic alkylating mutagen cyclophosphamide (CP) revealed remarkable species differences in their mutagenic responses. With both test systems the sensitivities of the three species can be ranked into the order rat greater than mouse greater than Chinese hamster. More explicit results were obtained with the SCE test than with the micronucleus test within the same dose range. This may be due to the influence of species-related differences in the cytotoxic response to CP in the micronucleus test. These results show that clearly different mutagenic responses in different test species may be obtained in standard assays even with a compound which is metabolized in a very similar manner in all animal species. PMID- 3331681 TI - 4-Methoxyindole derivatives as nitrosable precursors of mutagens in Chinese cabbage. AB - Two indole compounds isolated from fresh Chinese cabbage were shown to be mutagen precursors that yielded direct-acting mutagens on treatment with nitrite. They were identified as 4-methoxyindole-3-acetonitrile and 4-methoxy-indole-3 aldehyde. When these compounds were treated with 50 mM nitrite at pH 3.0 for 1 h at 37 degrees C, 4-methoxyindole-3-acetonitrile induced 31,800 and 10,000 revertants of Salmonella typhimurium TA100 and TA98, respectively, per mg of mutagen precursor in the absence of S9 mix, and 4-methoxyindole-3-aldehyde induced 156,900 revertants of TA100 and 26,800 revertants of TA98 per mg in the absence of S9 mix. PMID- 3331682 TI - Formaldehyde-induced cytotoxic, genotoxic and mutagenic response in human lymphocytes and Salmonella typhimurium. AB - The incidences of chromatid-type aberrations and sister-chromatid exchanges were significantly increased in human lymphocytes treated with formaldehyde (FA) in vitro. In the presence of the mammalian metabolic activation system, i.e. S9 mix, the yields were reduced, although not to control levels. With S9 mix the structural chromosome damage induced by exposure to 1.0 mM FA was qualitatively and quantitatively identical to that induced by 0.05 mM cyclophosphamide (used as positive control for metabolic activation). Cell proliferation was clearly reduced with or without the presence of S9 mix. In a plate assay with Salmonella typhimurium strain TA100 in the absence and presence of S9 mix, a weak mutagenic response was observed. Using the pre-incubation method, FA induced without S9 mix a 1.6-fold and with S9 mix a 2.7-fold increase of revertant numbers over controls. PMID- 3331683 TI - Synthesis and mutagenicity of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10 oxide, microsomal metabolites of 1-nitropyrene. AB - [4,5,9,10-(3)H]1-Nitropyrene was incubated with liver microsomes prepared from guinea pigs treated with Aroclor 1254 and the products were examined by h.p.l.c. The previously reported metabolites, 1-nitropyrene trans-4,5-dihydrodiol, 1 nitropyrene trans-9,10-dihydrodiol, and 3-, 6-, and 8-hydroxy-1-nitropyrene were detected. In addition, h.p.l.c., nuclear magnetic resonance and mass spectral analyses indicated the presence of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10 oxide. The epoxide hydrase inhibitor, 1,2-epoxy-3,3,3-trichloropropane, decreased the concentration of the 4,5- and 9,10-dihydrodiols in the microsomal incubations and increased the concentration of their corresponding oxides. Reaction of 1 nitropyrene with m-chloroperoxybenzoic acid gave a mixture of 1-nitropyrene 4,5 oxide and 1-nitropyrene 9,10-oxide, which was separated by chromatography. The mutagenicity of the oxides was determined in Salmonella typhimurium strains TA98, TA98NR, and TA98/1,8-DNP6, both with and without exogenous activation by a rat liver homogenate fraction (S9). In the absence of S9, both oxides showed maximum activity in TA98, slightly decreased mutagenicity in the acetylase-deficient strain TA98/1,8-DNP6, and much reduced activity in the nitroreductase-deficient strain, TA98NR. When assayed in the presence of S9, 1-nitropyrene 4,5-oxide had maximum mutagenicity in TA98, and was 50 and 95% less mutagenic in TA98NR and TA98/1,8-DNP6, respectively. 1-Nitropyrene 9,10-oxide had a similar strain sensitivity, except that its total mutagenicity was lower. Since 1-nitropyrene is metabolized by oxidative pathways in vivo, these K-region oxides may contribute to the toxicities elicited by this compound. PMID- 3331684 TI - In vivo sister chromatid exchange and micronucleus induction studies with 1,3 butadiene in B6C3F1 mice and Sprague-Dawley rats. AB - Male B6C3F1 mice and Sprague-Dawley rats were exposed for 2 days, 6 h/day to 1,3 butadiene (BD) by inhalation (nose only) and their bone marrow cells were evaluated for the induction of micronuclei (MN) and sister chromatid exchanges (SCEs). A significant dose-dependent increase in MN induction was observed in mice. At 100 p.p.m., the frequency of micronucleated polychromatic erythrocytes was 6-fold above control with a maximal induction of 38-fold at 10,000 p.p.m. A significant increase in SCEs was also observed in mouse bone marrow cells starting at 100 p.p.m. with a 4-fold increase over the control evident at 10,000 p.p.m. The highest tested no observed effect level for both endpoints was 50 p.p.m. In contrast, rat bone marrow cells did not exhibit significant increases in micronucleated polychromatic erythrocytes or SCEs. These results indicate that BD is genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats to BD carcinogenicity. PMID- 3331685 TI - Cycloheximide suppresses the enhancing effect of sodium arsenite on the clastogenicity of ethyl methanesulphonate. AB - Post-treatment with sodium arsenite synergistically increases the chromosomal aberrations induced by ethyl methanesulphonate (EMS). We have now provided evidence to show that the enhancing effect of sodium arsenite on the incidence of chromatid breaks and chromatid exchanges induced by EMS in Chinese hamster ovary cells can be suppressed by protein synthesis inhibitors, cycloheximide and puromycin. The most effective time period for cycloheximide or puromycin to suppress the co-clastogenic activity of sodium arsenite was during the middle 6 h in an 18-h incubation time after a 2-h treatment with EMS. The results suggest that the co-clastogenicity of sodium arsenite may require protein synthesis. PMID- 3331686 TI - A mismatch repair-based model can explain some features of u.v. mutagenesis in yeast. AB - Our studies on the REV2-dependent processes of DNA repair and u.v. mutagenesis in yeast are summarized and compared with the general features of DNA damage-induced mutagenesis in yeast. On the basis of the data available, we propose that mismatch repair is an essential process in u.v. mutagenesis. We assume that a photoproduct site in double-stranded DNA can be handled as a replicative mismatch leading to misinsertion opposite the lesion. PMID- 3331687 TI - Decreased u.v. mutagenesis in an excision-deficient mutant of yeast. AB - The u.v.-sensitive rad4 mutant of yeast was found to decrease u.v.-induced reversion in the cdc8 and lys2 loci. Survival curves obtained following u.v. irradiation and u.v.-induced reversion in rad4, cdc8 and cdc8rad4 double mutants show that cdc8 is epistatic to rad4 and belongs to the 'rad3' epistasis group. A study of u.v.-induced reversion in the thermosensitive cdc8 mutant at the restrictive temperature (prevents DNA synthesis) and at the permissive temperature (DNA synthesis takes place) indicates the essential role of DNA replication in u.v.-induced mutagenesis. PMID- 3331688 TI - The micronucleus assay in exfoliated cells of the human buccal mucosa. AB - The frequency of micronuclei resulting from chromosome breaks, and that of micronuclei deriving from spindle disturbances was determined in exfoliated cells of the human buccal mucosa in 50 normal individuals. Several confounding factors, such as age, smoking habits, alcohol consumption, etc., were taken into account. While the frequencies of micronuclei resulting from chromosome breaks and of cells with this kind of micronuclei were about double in smokers as compared with non-smokers, the difference being highly statistically significant, the frequencies of cells with spindle disturbances were almost the same in the two groups. No statistically significant correlation was found for any of the other variables examined. In two patients suffering from cancer of the oral cavity the variation of the frequency of the micronuclei during the progress of radiotherapy and following its interruption was determined. It was found that gamma rays induced only micronuclei resulting from chromosome breaks, whose frequency increased linearly with the applied dose, and was lowered to the initial background level 7-12 days after the end of radiotherapy. PMID- 3331689 TI - Mutagenic activity of carbon black dyes used in the leather industry. AB - Seven carbon black pastes used as commercial leather dyes were tested for their mutagenicity in the Salmonella/microsome test (TA98 and TA100 strains). All the samples assayed either directly or after extraction with a 30-min sonication in benzene were devoid of mutagenicity both in the presence and absence of a metabolic activation preparation. After a 48-h extraction with boiling toluene in a Soxhlet apparatus, four samples were mutagenic in TA98 strain in the presence of S9 mix. The activity ranged from 1.3 to 9.6 induced revertants/mg equivalent of extract. A weak direct mutagenic activity in strain TA98 was shown by one extract. Polycyclic aromatic hydrocarbons (PAH) were determined in the toluene extracts by high resolution gas chromatography/mass spectrometry. The presence of PAH could explain the mutagenicity of only one sample (8.79 micrograms of total PAH/100 mg equivalents of extract), while low or undetectable levels of PAH were found in the other mutagenic extracts. The mutagenic activity was evident only after a vigorous extraction process, thus a low bioavailability of the mutagens present in these compounds is suggested. PMID- 3331690 TI - Chromosome aberrations induced by nitro-, nitroso- and aminopyrenes in cultured Chinese hamster cells. AB - Nitropyrenes are a class of polycyclic hydrocarbons that have been shown to be potent point mutagens in the Salmonella/mammalian microsome assay. However, relatively few data have been published on their ability to induce chromosome aberrations. In this paper we report the cytogenetic activity of 1-nitropyrene, 1 nitrosopyrene, and 1-aminopyrene in cultured Chinese hamster cells (Don:Wg3h). Following treatment with 1-nitrosopyrene, high levels of both chromosome and chromatid types of aberrations were induced, the most notable effect being an increase in chromatid exchanges. Much weaker, but statistically significant, responses were also obtained for 1-nitropyrene and 1-aminopyrene. PMID- 3331691 TI - Mutagenicity of procarbazine for V79 Chinese hamster fibroblasts in the presence of various metabolic activation systems. AB - Even though procarbazine is mutagenic in most in vivo systems, a number of in vitro assays failed to indicate a positive effect. Since inappropriate metabolic activation in vitro is one explanation for these findings, the effects of procarbazine on V79 Chinese hamster fibroblasts in the absence and in the presence of either an S9 liver homogenate or hepatocytes from male rats were evaluated. The influence of enzyme induction was studied by performing experiments using S9 and hepatocytes both from non-treated and from Aroclor 1254 treated rats. Serum from procarbazine-treated rats was also tested for mutagenicity. Cytotoxicity was not strongly influenced by the presence of either S9 or hepatocytes, irrespective of whether Aroclor-induced or non-induced preparations were used. Without a metabolic activation system, and in the presence of S9 from non-induced animals, a weak mutagenic effect, i.e. an increased frequency of thioguanine-resistant clones, was observed in the cytotoxic dose range of 6000 micrograms/ml. In the hepatocyte-mediated assay, 2-6 micrograms/ml procarbazine proved to be mutagenic. Using the hepatocyte-mediated assay, a decrease in mutagenicity in the cytotoxic dose range was observed, reaching, at 6000 micrograms/ml in the case of hepatocytes from non-induced animals, a value almost identical to that observed without a metabolic activation system. Thus testing chemicals in the cytotoxic dose range only might lead to false conclusions, particularly if hepatocytes were used for metabolic activation. The use of liver preparations from Aroclor-pretreated rats led to much stronger mutagenic responses than those caused by non-induced material.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331692 TI - Performance of short-term tests for detection of human carcinogens. AB - The performance of short-term tests for detection of carcinogens has been validated by several investigators and international collaborative programmes. A large number of chemicals have been tested by the Salmonella/microsome assay and high values of sensitivity and specificity, often greater than 70%, were reported. For 71 human carcinogens classified in Groups 1, 2A and 2B by the International Agency for Research on Cancer (IARC), the Salmonella/microsome test showed a sensitivity of 62.1%: 36 were positive out of 58 chemicals tested. Similar or rather higher values were obtained with Escherichia coli mutation assay (72.0%, 18/25), mutation assays in fungi (78.9%, 30/38), mutation assays in insects (65.7%, 23/35), and assays measuring DNA damage in prokaryotes (80.5%, 33/41). In assays using mammalian cells, tests on chromosomal anomaly showed a relatively high sensitivity: 61.7% (29/47) in chromosomal structural aberration assays and 80.6% (25/31) in sister chromatid exchange (SCE) assays. Comparable values were also obtained in mutation assays of mammalian cells (73.0%, 27/37) and cell transformation assays (87.5%, 21/24). Results of monitoring of exposed populations did not necessarily show a high sensitivity to human carcinogens (44.4%, 12/27). Human carcinogen data were further analysed in order to find a combination of tests which may increase the predictive value. Among human carcinogens, 17 chemicals are not mutagenic in the Salmonella/microsome assay. Although 9 of 17 chemicals (asbestos, hormones, chlorinated compounds and 1,4 dioxane) were not positive in any short-term assays, some gave positive results in a variety of assays, e.g. arsenic and benzene were positive in assays of chromosomal anomaly in mammalian cells in vitro. Combinations of the Salmonella/microsome assay with certain tests using mammalian cells were found to increase the sensitivity significantly. Chromosomal anomaly assays of mammalian cells in vitro seem to be most relevant for detection of human carcinogens when used in combination with the Salmonella/microsome assay. PMID- 3331693 TI - Prediction of carcinogenic potency by short-term genotoxicity tests. AB - Past attempts to correlate carcinogenic potencies of chemicals with potencies in causing mutations or other endpoints in short-term genotoxicity tests have found quantitative correlations to be weak except for restricted classes of chemicals. We have classified 379 chemicals on the basis of the rodent carcinogenic potencies calculated by Gold and co-workers as strong carcinogens, moderate carcinogens, weak carcinogens, or non-carcinogens, and have compared the qualitative results of short-term tests (positive or negative) for each of the four classes of chemicals. For most of the short-term tests analyzed, the proportion of positive results increased with carcinogenic potency, being highest for strong carcinogens, lower for moderate carcinogens, lower still for weak carcinogens, and least for non-carcinogens. This differential sensitivity based on carcinogenic potency implies that short-term test responses could be used to predict the carcinogenic potency of unknown chemicals. We have quantified these predictions using Bayesian analysis so that positive or negative results in short term tests can be interpreted as predicting that a chemical may be a strong carcinogen, a moderate carcinogen, a weak carcinogen, or a non-carcinogen. Possible screening strategies based on these predictions are discussed. PMID- 3331694 TI - Effect of tryptamine on the mutagenic activity of 2-amino-3-methylimidazo(4,5-f) quinoline (IQ) and related azaarenes in the Ames test. AB - The bioactivation of the azaarenes 2-amino-3-methylimidazo(4,5-f) quinoline (IQ), 2-amino-3,4-dimethylimidazo(4,5-f) quinoline (MeIQ) and 2-amino-3,8 dimethylimidazo(4,5-f) quinoxaline (MeIQx) to mutagens by hepatic S9 preparations derived from Aroclor-pretreated Wistar rats was inhibited by tryptamine (2-50 microM). However, with similar preparations derived from Sprague-Dawley rats, bioactivation of IQ and MeIQx was less markedly inhibited by tryptamine while metabolic activation of MeIQ was enhanced. In the absence of cytosol, activation of IQ by microsomal preparations of both rat strains was inhibited by tryptamine. Cytosolic fractions from both rat strains were incapable of activation of IQ per se but increased the mutagenicity of the microsomal metabolite(s). This potentiation of the mutagenic activity by cytosol derived from Wistar rats was also inhibited by tryptamine whereas no significant inhibition was observed with cytosolic preparations from Sprague-Dawley rats. There appear to be two alternative pathways of microsomal metabolism of IQ: a tryptamine-sensitive pathway, probably involving the formation of the N-hydroxymetabolite; and a tryptamine-insensitive pathway producing weakly mutagenic or non-mutagenic metabolites which are activated to a potent mutagen by the cytosol. The tryptamine-insensitive pathway appears to be the major route of activation of the azaarenes in microsomal preparations from Sprague-Dawley rats and the principal activation route for MeIQ in both rat strains. PMID- 3331695 TI - Inactivity of methylene chloride in the mouse bone marrow micronucleus assay. AB - Methylene chloride (MC) has been evaluated for its ability to induce micronucleated polychromatic erythrocytes (MPEs) in the bone marrow of treated mice. Groups of five male and five female C57BL/6J/Alpk mice were exposed, by gavage, to doses of 4000, 2500 and 1250 mg/kg MC in corn oil, the highest dose level being selected to be the maximum tolerated dose. Bone marrow samples were taken 24, 36, 48 and 72 h after dosing. No significant increases in the incidence of MPEs over controls were observed for any of the test groups, and it is concluded that MC is not clastogenic in this assay. PMID- 3331697 TI - Germ cell assays in routine mutagenicity testing. PMID- 3331696 TI - Implications of germ cell cytogenetic tests in the regulatory process. AB - As tests for germ cell cytogenetics are not prominent in any regulatory guidelines for assessment of product safety, it was decided to investigate the regulatory implications of germ cell cytogenetics by sending detailed questionnaires to contacts in 12 different regulatory agencies. The questionnaires covered three main sections: the basic principles governing if and when germ cell cytogenetics might be an acceptable alternative to a dominant lethal, heritable translocation or mouse specific locus test; what details of protocol would be desired in a male or female germ cell cytogenetic assay; the presentation of data and the criteria for a valid study and a positive result. Replies were received from seven of those contacted and some of the responses were personal rather than official. They may be summarized as follows. (i) Germ cell tests are rarely requested as a matter of course. Positive results in in vivo somatic cell cytogenetic tests and/or problems indicated in fertility/reproduction studies would suggest to some agencies a need for germ cell tests, but others believe they do not contribute to the assessment of risk for man. (ii) Where germ cell tests are indicated, a dominant lethal test (most often) or heritable translocation test (sometimes) would be seen as helpful in elucidating germ cell effects; the mouse specific locus test is rarely requested due to the large numbers of animals involved and the small number of laboratories with the relevant expertise. (iii) As most widely used germ cell cytogenetic assays do not detect inherited mutations or effects on meiotic processes, they were not readily accepted as alternatives.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331698 TI - Synthesis and bacterial mutagenicity of the cyclopenta oxides of the four cyclopenta-fused isomers of benzanthracene. AB - Many polycyclic aromatic hydrocarbons containing peripherally fused cyclopenta rings are believed to be activated primarily by epoxidation of the cyclopenta ring. The cyclopenta epoxides of a series of four cyclopenta benzanthracene derivatives, benz[e]aceanthrylene-5,6-oxide, benz[j]aceanthrylene-1,2-oxide, benz[l]aceanthrylene-1,2-oxide and benz[k]acephenaceanthrylene-4,5-oxide were synthesized from their parent hydrocarbons by formation of the bromohydrin followed by dehydrobromination, and characterized by u.v.-vis, and 1H n.m.r. spectroscopy and mass spectrometry. The mutagenicity of these compounds was investigated in the Ames plate incorporation assay with Salmonella typhimurium strain TA98. All the oxides were active without exogenous metabolic activation (170-320 His+ revertants per nanomole) and also toxic above 0.5 microgram/plate. Addition of S9 protein did not increase, and generally decreased, the mutagenicity of the oxides, while toxicity was largely unchanged. These results are consistent with the postulated role of cyclopenta oxides as major contributors to the mutagenicity of the parent compounds in the Ames assay. PMID- 3331699 TI - U.v.-induced and N-methyl-N'-nitro-N-nitrosoguanidine-induced mutagenesis in Bacillus thuringiensis. AB - The lethal and mutagenic effects of u.v. light and N-methyl-N'-nitro-N nitrosoguanidine (MNNG) on Bacillus thuringiensis were investigated. Lethality studies demonstrated that B. thuringiensis was relatively sensitive to these agents. This bacterium was mutated at the rifampicin resistance marker by u.v. light and to a lesser extent by the direct acting alkylating agent MNNG. One mutant selected for its greater sensitivity to u.v. light expressed a higher frequency of mutagenesis after u.v. light treatment and appeared to be defective in an excision repair pathway. However, this mutant was only slightly mutable by MNNG in comparison with the wild-type strain. This unusual phenotype does not yet have a parallel among the radiation sensitive mutants described in other bacterial species. PMID- 3331700 TI - The bone marrow clastogenicity of eight halogenated benzenes in male NMRI mice. AB - Eight widely used halogenated benzenes, including bromobenzene (BB), chlorobenzene (CB), three isomers of dichlorobenzene (DCB) and three isomers of trichlorobenzene (TCB) were tested for acute toxicity (LD50) and clastogenicity in 8-week-old NMRI mice by intraperitoneal administration. Four doses of each chemical (up to 70% of LD50) were tested for clastogenic activity. Each compound was administered in two equal doses, 24 h apart. Increased formation of micronucleated polychromatic erythrocytes, observed in femoral bone marrow, 30 h after the first injection, was considered to be due to the clastogenic activity of the test compound. All the halogenated benzenes tested were found to be clastogenic (P less than 0.01). The highest clastogenic activities were induced by m-DCB and BB. Among the three isomers of DCB, m-DCB significantly (P less than 0.05) induced more micronuclei than o-DCB or p-DCB. No significant differences were found between the clastogenic activities of TCB isomers. PMID- 3331701 TI - A simple and reliable in vitro test system for the analysis of induced aneuploidy as well as other cytogenetic end-points using Chinese hamster cells. AB - Although aneuploidy is a serious human health problem, the experimental methodology devised until now to study the mechanisms involved in the induction of aneuploidy and for the screening of aneuploidy-inducing agents has not been so much employed to have the necessary validation. A procedure using primary cell cultures of Chinese hamster embryo cells grown on cover glasses is described. To avoid the excessive scattering and subsequent loss of chromosomes, a hypotonic treatment with a 0.17% sodium chloride solution, at room temperature, followed by in situ fixation has been standardized. This procedure improves the method through the reduction of the spontaneous frequency of aneuploid cells. Experiments carried out with cells treated with X-rays, X-rays plus caffeine, and the synthetic estrogen diethylstilbestrol (DES) demonstrated the accuracy of the system since the average chromosome number remained constant in spite of the induction of high frequencies of aneuploid cells. Moreover, the method allows for the analysis of other cytogenetic endpoints such as anaphase-telophase alterations, structural chromosome aberrations or sister chromatid exchanges. PMID- 3331702 TI - Activation of 2-amino-3-methylimidazo (4,5-f) quinoline in rat and human hepatocyte/Salmonella mutagenicity assays: the contribution of hepatic conjugation. AB - The capacity of human liver S9 and hepatocytes to metabolically activate 2-amino 3-methylimidazo (4,5-f) quinoline (IQ) in Salmonella mutagenicity assays more closely resembles that of preparations from Aroclor-induced rat than control rat. The extent to which hepatocyte conjugating enzymes contribute to activation in these assays has been studied. Omission of sulphate or addition of a 'specific' sulphotransferase inhibitor (2,6-DCNP) did not significantly reduce mutagenicity, nor did PAPS enhance S9-mediated bacterial mutagenicity. Conversely, mutagenicity was significantly inhibited by PCP (an inhibitor of both sulphotransferase and acetyltransferase) and an acetylation-deficient Salmonella (TA98/1,8DNP6) was unresponsive to the mutagenicity of IQ. These data suggest that acetylation but not sulphation is important in IQ bacterial mutagenesis. The addition of acetyl CoA, PAPS-generating system or ATP paradoxically reduces the mutagenicity of IQ in S9/Salmonella TA98 assays. Therefore, activation by esterification in hepatocytes does not contribute to the mutagenicity of IQ in Salmonella typhimurium possibly due to restricted access of conjugates into the bacterial cell. PMID- 3331703 TI - The interaction of statistical significance, biology of dose-response and test design in the assessment of genotoxicity data. AB - The most useful function of statistical significance in genetic toxicology is to separate weakly positive from negative data. To achieve this objective, the experimental system, design and analysis must be considered as a whole and not as separate entities. Assumptions underlying statistical methods should be checked for applicability to the biology of the test. The number and arrangement of samples and dose levels must be organized to suit the selected statistical method. The number of observations in the test and in each sample will depend on the smallest increase of biological importance which should be detected as significant (at a selected value for alpha error) and the maximum acceptable chance of failing to detect this increase as significant (beta error). Generally, a few dose levels and a high degree of replication are desirable with a repeat test if practical. In the analyses of data it is particularly important to adapt the statistics if there are multiple comparisons. Even after correct determination of significance, interpretation can be difficult because of possible experimental artefacts and chance errors plus the impossibility of proving a negative result. PMID- 3331704 TI - U.v. mutagenesis in yeast and Escherichia coli. PMID- 3331705 TI - The predictivity of animal bioassays and short-term genotoxicity tests for carcinogenicity and non-carcinogenicity to humans. AB - The successful use of surrogate tests to predict whether a chemical may be carcinogenic to humans requires that the tests be both sensitive (few false negatives) and specific (few false positives). To assess specificity, results for non-carcinogens must be compared. Although no chemicals have been definitively shown not to cause cancer in humans, we have identified 29 chemicals for which some evidence of non-carcinogenicity exists in evaluations by the International Agency for Research on Cancer. Twenty of these probable non-carcinogens have been tested for rodent carcinogenicity in animal bioassays; 19 were positive and only one was negative, indicating that the specificity of animal bioassays is low. The sensitivity of animal bioassays, however, is very high: all definite human carcinogens adequately tested were positive. Most short-term tests which measure genotoxicity or transformation also had low specificity; however, four tests gave predominantly negative results for probable human non-carcinogens as well as predominantly positive results for definite human carcinogens. These results are based on comparison of small numbers of chemicals, but do suggest the need for more investigation of the relationships of genotoxicity and rodent carcinogenicity to carcinogenicity in humans. PMID- 3331706 TI - Mammalian male germ cell cytogenetics. AB - The methods used for the detection of chemically induced chromosome damage in male germ cells are discussed. These tests have been divided into direct and indirect cytogenetic methods. The direct methods assess chromosome damage in the dosed animal but analysis is restricted to the dividing spermatogonia and spermatocytes. Using indirect methods, chromosome damage is assessed in the F1 progeny of the dosed male and analysis covers all germ cell stages. Both methods can provide evidence of germ cell exposure but the data obtained from the indirect tests are considered more relevant since a positive result clearly constitutes unequivocal evidence of transmitted damage. The analysis of one-cell embryos from matings involving dosed parents is considered to be the most useful indirect test system since both structural and numerical aberrations in male and female F1 offspring can be assessed. Although relevant to the assessment of mutagenic hazard, the technically demanding methods used in the germ cell techniques prevent their use for preliminary screening programmes. PMID- 3331708 TI - Synthesis and mutagenicity of 3-halogenated and 3,3',5,5'-tetrahalogenated benzidines. AB - 3-Fluorobenzidine (FBz), 3-chlorobenzidine (ClBz), 3-bromobenzidine (BrBz), 3,3',5,5'-tetrafluorobenzidine (F4Bz), and 3,3',5,5'-tetrachlorobenzidine (Cl4Bz) were synthesized and tested for their ability to revert Salmonella typhimurium. F4Bz was the only compound to show direct-acting mutagenicity and was equally potent in strain TA98 and the acetylase-deficient strain TA98/1,8-DNP6. In the presence of hamster liver S9, all compounds except Cl4Bz were mutagenic. The relative mutagenicities in TA98 were FBz greater than ClBz greater than BrBz greater than F4Bz greater than Bz greater than Cl4Bz = 0. In TA98/1,8-DNP6 the trend was F4Bz approximately BrBz approximately ClBz greater than FBz greater than Bz greater than Cl4Bz = 0. PMID- 3331707 TI - Refinement of a T-lymphocyte cloning assay to quantify the in vivo thioguanine resistant mutant frequency in humans. AB - Cell cloning by limiting dilution in 96-well microtiter plates has been employed to isolate colonies of human T-lymphocytes resistant to the purine analogue, 6 thioguanine (TG). These colonies show stability of the TG-resistant (TG1) phenotype, lack hypoxanthine guanine phosphoribosyl transferase (HPRT) activity and thus appear to be the result of in vivo somatic cell mutation events. In order to employ this T-lymphocyte cloning assay for quantitative determination of the in vivo TGr mutant frequency in humans, we have defined the optimal conditions for T-cell colony formation with both nonselected and TG-selected cells. The parameters investigated include medium, serum, amount of the mitogen phytohaemagglutinin, amount of T-cell growth factor (TCGF) and the number of irradiated feeder or accessory cells. Under the optimal conditions, the fraction of positive wells is proportional to the number of cells plated per well with both nonselection and TG selection conditions. T-cell cloning efficiencies therefore are independent of inoculum size. There was some evidence for a decline in TGr mutant cell cloning at densities greater than 2 x 10(4) cells per round bottom well, possibly due to metabolic cooperation between wild-type and mutant cells. The conditions defined in this study appear to provide a quantitative measurement of the in vivo TGr mutant frequency in human T-lymphocytes. PMID- 3331709 TI - Dedication (Gordon Mayer Tomkins). PMID- 3331712 TI - The inhibition of phosphoenolpyruvate carboxykinase (guanosine triphosphate) gene expression by insulin is not mediated by protein kinase C. AB - The role protein kinase C plays in the regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by insulin and phorbol esters was studied in H4IIE hepatoma cells (ATCC CRL 1548). The combined effects of phorbol 12 myristate 13-acetate (PMA) and insulin on the suppression of mRNA coding for PEPCK (mRNAPEPCK) synthesis were additive. A potent inhibitor of both cyclic nucleotide-dependent protein kinases and protein kinase C, 1-(5 isoquinolinesulfonyl)-2-methylpiperazine, inhibited the cAMP and PMA-mediated regulation of mRNAPEPCK synthesis, but did not affect the action of insulin. Desensitization of the protein kinase C pathway by exposure to PMA for 16 h abolished the subsequent action of the phorbol ester, but did not affect insulin- or cAMP-mediated regulation of PEPCK gene expression. We conclude that insulin suppresses PEPCK gene expression independently from the protein kinase C-mediated pathway used by phorbol esters. PMID- 3331711 TI - Human preproparathyroid hormone synthesized in Escherichia coli is transported to the surface of the bacterial inner membrane but not processed to the mature hormone. AB - cDNA encoding human preproPTH (hpreproPTH) was expressed in Escherichia coli to study the processing of the precursor to hPTH and its secretion by the bacterial secretory apparatus. We first constructed hybrid genes that differed randomly in the distance between the E. coli lac promoter's ribosomal binding site and DNA encoding a fusion protein with beta-galactosidase activity and the prepro sequence of hpreproPTH on the aminoterminus. Starting with clones identified as efficient producers of beta-galactosidase on indicator agar plates, the coding sequence for hpreproPTH was reconstituted intact. In a different construction we placed the hpreproPTH coding sequence downstream from the lac promoter at a distance of 12 base pairs from the ribosomal binding site. PTH immunoreactive proteins from multiple clones were identified by protein gel electrophoresis and by protein microsequencing. PTH-related proteins encoded by different plasmids were shown to be hpreproPTH with amino-terminal extensions of either two or four amino acids and as authentic hpreproPTH. Two hPTH fragments, hPTH(3-84) and hPTH(8-84), were also observed. The trypsin accessibility of hpreproPTH and of the two hPTH fragments in pulse-chase, cell-fractionation experiments using intact and lysed spheroplasts lets us conclude that the mammalian signal sequence directs hpreproPTH to the surface of the spheroplast membrane but is not appropriately cleaved by the signal peptidase. PMID- 3331710 TI - Insulin action in normal and protein kinase C-deficient rat hepatoma cells. Effects on protein phosphorylation, protein kinase activities, and ornithine decarboxylase activities and messenger ribonucleic acid levels. AB - Insulin and tumor-promoting phorbol esters such as phorbol 12-myristate 13 acetate (PMA) share some biological activities in normal hepatocytes and in some lines of cultured hepatoma cells. To investigate the possibility that some of these common effects might involve a common pathway, we examined the effects of insulin and PMA on several biological processes in normal and protein kinase C deficient H4IIE rat hepatoma cells. Protein kinase C deficiency was achieved by preincubating the cells in high concentrations of PMA, and was documented by direct enzyme measurement in soluble and particulate cellular fractions, and by analysis of immunoreactive protein kinase C concentrations in whole cellular homogenates. In the protein kinase C-deficient cells, the following actions of insulin remained at near normal levels: stimulated phosphorylation of the ribosomal protein S6; activation of a ribosomal S6 protein kinase; and increases in ornithine decarboxylase activity and mRNA accumulation. PMA stimulated all of these responses in the normal cells, but none of them in the PMA-pretreated cells. We conclude that insulin can exert some of its actions in a normal manner in protein kinase C-deficient H4IIE hepatoma cells (ATCC CRL 1548) and that some of the actions insulin holds in common with PMA may be due to common activation of one or more distal pathways. A candidate for such a distal step is activation of the ribosomal protein S6 protein kinase. PMID- 3331713 TI - Regulation of cloned prolactin-inducible genes in pigeon crop. AB - Polyadenylated RNA from PRL-stimulated pigeon (Columba livia) crop was used as template to produce a cloned cDNA library in plasmids. The library was screened by differential hybridization against labeled nucleic acid populations representative of both unstimulated and PRL-stimulated crop tissue. By this method four independent clones coding for PRL-inducible mRNAs were identified. The regulation of these four genes ranged from modest (2- to 3-fold) to major (greater than 70-fold). A clone designated DA4 was complimentary to the most markedly stimulated crop mRNA. This mRNA encoded a polypeptide with a molecular weight of 35,500 which corresponds with the major induced protein synthesized in vivo. Messenger RNADA4 stimulation was dose dependent showing maximal induction by ovine PRL systemic injections in the 200 micrograms/day range. Above this dose PRL was less effective. The onset of mRNADA4 accumulation after a single PRL injection was rapid with statistically significant levels occurring by 3 h. Several lactogenic type hormones, but not an ungulate GH, were potent inducers of mRNADA4. The receptor responsible for mRNADA4 stimulation responds to mammalian lactogens (ovine PRL, human GH, human placental lactogen, bovine placental lactogen) and also can be blocked by an antibody to rabbit mammary gland PRL receptors. These results argue that regulation of pigeon crop gene expression (specifically mRNADA4 may be a relatively simple model of lactogenic hormone mechanisms. PMID- 3331714 TI - In memoriam Mortimer B. Lipsett. PMID- 3331716 TI - [Juvenile periodontitis, 2: Therapeutic aspects]. PMID- 3331715 TI - [Experimental study of the strength of the resin-metal bond for use in fixed partial denture with resin]. PMID- 3331717 TI - [Relation between Bleeding Time Index values and the number of polymorphonuclear leukocytes in washings of periodontal pockets]. PMID- 3331718 TI - [Cephalometric analysis in maxillo-facial surgery (study of a computerized system of diagnostic analysis of maxillofacial abnormalities]. PMID- 3331719 TI - [Cephalometric analysis in maxillofacial surgery. A proposed computerized cephalometric analysis in lateral projection for study of maxillofacial abnormalities]. PMID- 3331720 TI - [Rapid palatal expansion: rhinomanometric study. 4]. PMID- 3331721 TI - [Computerized management as an adjunct to rhinomanometry]. PMID- 3331722 TI - [Cephalometric analysis in maxillofacial surgery. A proposed computerized analysis in antero-postero projection for study of maxillofacial abnormalities]. PMID- 3331723 TI - [Effect of prostacyclin on the ultrastructure of the cerebral cortex of rabbits after total 20-minute cerebral ischemia. I. Neurons and neuropil]. PMID- 3331724 TI - [Effect of prostacyclin on the ultrastructure of the cerebral cortex of rabbits after total 20-minute cerebral ischemia. II. Astrocytes and blood vessels]. PMID- 3331725 TI - [Acquired immunodeficiency syndrome (AIDS) and anesthesia-resuscitation]. PMID- 3331726 TI - Hepatic retinol metabolism: role of the various cell types. PMID- 3331728 TI - Familial hypertriglyceridemia aggravated by diabetes and drugs. PMID- 3331727 TI - Lean body mass and food-induced thermogenesis in obesity. PMID- 3331729 TI - The New England Journal of Medicine, Volume 276, January 19, 1967: Fat transport in lipoproteins--an integrated approach to mechanisms and disorders. By Donald S. Fredrickson, Robert I. Levy, Robert S. Lees. PMID- 3331730 TI - Effect of xenobiotics on hepatic vitamin A storage. PMID- 3331731 TI - The cost of renal transplants. AB - Patient records were examined for the 12 months immediately following a renal transplantation in 29 patients admitted to the department of nephrology of the Christchurch Hospital. Data were collected on their use of health care facilities and resources during the period including details of inpatient stays, outpatient visits, dialysis, drugs and diagnostic procedures. From this information estimates were made of the average cost of the treatment and the total annual cost of renal transplantation in New Zealand. The average cost of treatment during the first year following renal transplantation was estimated to be +16,717. For the country as a whole it was estimated that the annual cost of first year renal transplant therapy was +1,270,492 in 1986 prices. PMID- 3331732 TI - Computer processing of ocular photographs--a review. AB - The use of digital image processing for enhancement and analysis of ocular photographs is a growing field of clinical research and application. The value of ocular image analysis and the requirements for acquisition and storage of digital images are outlined. A number of techniques for image enhancement and analysis are introduced, and their applications to lens and fundus images are reviewed. PMID- 3331733 TI - The Marton Lecture: Ocular manifestations of systemic medication. AB - The probability of ocular adverse reactions to systemic medication is low but when a reaction does occur it is often associated with one or more special factors relating to the condition being treated, to the patient, and to the nature of the drug itself. Nevertheless the role of the optometrist in the monitoring, detection and reporting of adverse reactions is important and is recognized by the College reporting scheme. A selection of the type of reactions that may be encountered in general optometric practice is reviewed. The reactions range from the relatively innocuous anticholinergic effects of the benzodiazepine tranquillizers to the more serious corneal, lens and retinal changes that may be associated with the corticosteroids, phenothiazines and chloroquine. PMID- 3331734 TI - A review of antibiotic prophylaxis for open fractures. AB - A review of the literature strongly supports the use of antibiotic prophylaxis in open fracture management. Because of their broad spectrum of activity, cephalosporins are the drugs of choice in cases of orthopaedic trauma. The extent of the injury determines the appropriate agent and the length of time it should be given. Patients with Type 1 or Type 2 fractures require only brief treatment (one preoperative and two postoperative doses) with an agent that has good antistaphylococci activity. Cephalothin, cefazolin, cefamandole or cefuroxime are recommended. Type 3 fractures present a much greater problem because of the risk of gram-negative infection. The marked activity of cefuroxime, cefamandole, and cefotaxime against these organisms recommends their use in such cases. Combination regimens with aminoglycosides require further study to define added efficacy and to define appropriate dosing regimens. We advocate that antibiotic prophylaxis should be given as soon as possible to all patients with open fractures and Type 3 fractures, and that prophylaxis should continue until 48 hours after adequate soft tissue coverage is achieved. PMID- 3331735 TI - Overview of osteomyelitis. AB - Osteomyelitis is becoming a more common infection. This increase has been associated with an increase in the number of orthopaedic surgical procedures and with severe bone trauma. The etiology of osteomyelitis is also changing, with more gram-negative and more polymicrobial infections due to both gram-positive and gram-negative pathogens. Underlying diseases such as diabetes mellitus, peripheral vascular and sickle cell disease are associated with a poor cure rate when treated with antibiotics. The emergence of resistant strains of bacteria during the long-term treatment necessary for osteomyelitis has been documented, and continues to be a concern, as are the other side effects. PMID- 3331737 TI - Treatment of skin loss in the hand. AB - In treating skin loss of the hand, the surgeon must be aware of the placement of skin and scars, the unique quality of palmar skin, the tendency of skin grafts to hyperpigment, the need for pain-free and well-padded amputation stumps that are free of painful neuromata and poorly padded phalangeal remnants. Skin grafts, palmar skin loss, regional flaps, distant flaps and local flaps are discussed. The histology and function characteristics of normal skin of the hand are reviewed. PMID- 3331736 TI - Historical vignette #7. Waterbury and the hazards of prolonged radiation. PMID- 3331738 TI - Burns of the hand and wrist. Current concepts in diagnosis and treatment. AB - Correct acute care is critical in the treatment of burns of the hand, particularly in the younger patient in order to avoid complications that may interfere with the patient's quality of life and ability to be self-sufficient and self-supportive. Objectives of management are to prevent edema, prevent prolonged immobilization and poor position and prevent infection and preserve viable tissue. The various modalities that are used to achieve these objectives and how they may be individualized to meet the patient's specific needs are described and discussed. PMID- 3331739 TI - [Acute post-traumatic brain volume increase in the CT image]. PMID- 3331741 TI - [Ultrasonographic diagnosis of congenital hip dislocation]. PMID- 3331740 TI - [Metastatic tumors of the spinal canal in myelographic and computerized myelotomographic images]. PMID- 3331742 TI - [Usefulness of ultrasonography in the early diagnosis of congenital hip dysplasia. Preliminary report]. PMID- 3331743 TI - [Evaluation of the effectiveness of ultrasonographically monitored fine-needle aspiration biopsy in the diagnosis of focal changes in the liver and pancreas]. PMID- 3331744 TI - [Intravenous digital subtraction angiography of the arteries of the pelvis and legs]. PMID- 3331745 TI - [Cholescintigraphy using technetium 99m mebrofenin in the diagnosis of disorders of potency of the biliary tract. Preliminary report]. PMID- 3331747 TI - [Ultrasonic examination of the breast. I. Methods of examination used in ultrasonic mammography. II. Comparison of the values of USG mammography and roentgenological mammography in the diagnosis of diseases of the breast]. PMID- 3331746 TI - [Value of isotope scintigraphy in the diagnosis of diseases of the liver]. PMID- 3331748 TI - [Conditions of rational utilization of the magnetic resonance technic in Poland]. PMID- 3331749 TI - [Computer-assisted medical diagnosis]. PMID- 3331750 TI - [Selection of anodal voltage in osteoporosis]. PMID- 3331751 TI - [The Doctor Honoris Causa title from the Medical Academy in Poznan for Prof. Walter Frommhold]. PMID- 3331752 TI - [From the roentgenological image to MR. Radiological diagnosis and technical development]. PMID- 3331753 TI - Panic disorder. AB - We note the recent paradigm shift to sub-divide anxiety into endogenous and exogenous forms, with the former (panic disorder) being viewed as a genetically determined metabolic disorder. We examine some of the supportive evidence and note the limitations of an exclusive biological model for panic disorder. Drug and other therapies are considered briefly and attention is drawn to the pluralistic approaches used in specialized treatment centres in Australia. PMID- 3331754 TI - [Development of a treatment concept for care of posterior gap--an example of a patient with elongation of teeth 16 and 17]. PMID- 3331756 TI - [Corrective use of acid etch technic]. PMID- 3331755 TI - [Functionally stabilized support of anterior tooth implants using adhesive technic]. PMID- 3331757 TI - [Relief impression--a procedure for direct impression of flexible mouth mucosa]. PMID- 3331758 TI - [Prosthetic treatment of occlusal abrasion (I)]. PMID- 3331759 TI - [Prosthetic treatment of occlusal abrasion (II)]. PMID- 3331760 TI - [Preparation of a model for training in tooth cleaning in the area of periodontal treatment]. PMID- 3331761 TI - [Adhesive bridges for care of patients with cleft lip and palate after maxillofacial surgery and orthodontic treatment]. PMID- 3331763 TI - [PCF-polymer denture base]. PMID- 3331762 TI - [New veneering technics with the use of castable apatite-ceramic materials. II. Practical application]. PMID- 3331765 TI - [Tisastift, a new construction of a root post]. PMID- 3331764 TI - [Prosthesis framework/discoloration]. PMID- 3331766 TI - [Accuracy of SR-IVOCAP bite plates]. PMID- 3331767 TI - [Basic principles of prosthetics: Maryland bridges (I)]. PMID- 3331768 TI - [Basic principles of prosthetics: Maryland bridges (II)]. PMID- 3331769 TI - [Basic principles of prosthetics: Maryland bridges (III)]. PMID- 3331770 TI - [Changes in periodontology]. PMID- 3331771 TI - [Basic principles of prosthetics. Prosthetic aids (V)]. PMID- 3331773 TI - [Improved impressions with compression caps. Report of 10-year experience]. PMID- 3331774 TI - [Japan's historically prominent artificial tooth makers]. PMID- 3331772 TI - [Basic principles of prosthetics. Prosthetic aids (VIII)]. PMID- 3331775 TI - [Colorful instrument mosaic]. PMID- 3331776 TI - [Attachment casting technic--a cost favorable alternate solution]. PMID- 3331777 TI - [Function and esthetics--dental technical-physiological occlusal concept (II)]. PMID- 3331778 TI - [Finishing Heratec crowns]. PMID- 3331780 TI - [Preheating procedures for cristobalite containing impressions]. PMID- 3331779 TI - [Cost reduction proposal: patient-pass for denture]. PMID- 3331781 TI - [40th anniversary of the founding of the Periodontology Department]. PMID- 3331782 TI - [History, bibliography, museums (con't). The history of dentistry]. PMID- 3331783 TI - [Medieval themes]. PMID- 3331784 TI - [An anecdote apropos of the pedal engine]. PMID- 3331785 TI - [Past times. The Garengeot key]. PMID- 3331787 TI - [A school and its statues]. PMID- 3331786 TI - [A century of dental education]. PMID- 3331788 TI - [The function of the dentist in the army. (After an evaluation by an Argentinian military doctor in 1921)]. PMID- 3331789 TI - [Course in laboratory technics for dentists. 50th anniversary of its Creation]. PMID- 3331790 TI - [The Pecotche sisters in Argentinian dentistry]. PMID- 3331791 TI - [Remembering the great masters: Humberto Aprile]. PMID- 3331792 TI - [History, bibliography, museums (con't). History of dentistry]. PMID- 3331794 TI - [Heart transplantation in Spain: 1984-1986]. PMID- 3331793 TI - [The myth of heart transplantation]. PMID- 3331795 TI - [Heart transplantation at the Hospital de la Santa Creu i Sant Pau, Barcelona]. PMID- 3331796 TI - [Heart transplantation. Perspectives and the future, 1987]. PMID- 3331797 TI - [Detection of myocarditis using endomyocardial biopsy in candidates for heart transplantation]. PMID- 3331798 TI - [Detection using scintigraphy with monoclonal anti-myosin in recurring myocarditis treated with cyclosporin A in a heart transplant candidate]. PMID- 3331799 TI - [Psychiatric aspects of the evaluation of candidates for heart transplantation]. PMID- 3331800 TI - [Experimental heart transplantation: acute hemodynamic evaluation comparing 2 different methods of myocardial protection]. PMID- 3331801 TI - [Anesthetic management in heart transplantation]. PMID- 3331802 TI - [Endomyocardial biopsy in heart transplant patients treated with cyclosporin A]. PMID- 3331803 TI - [Lymphocyte subpopulations in peripheral blood in the diagnosis of heart rejection in patients treated with cyclosporin A]. PMID- 3331804 TI - [Echocardiographic study of the transplanted heart in patients treated with cyclosporin A]. PMID- 3331805 TI - [Selection and timing for inclusion of patients for transplantation: an essentially clinical decision]. PMID- 3331806 TI - [Sudden death as the only manifestation of rejection in the heart transplant patient treated with cyclosporin A]. PMID- 3331808 TI - [Isotopic ventriculography study of the behavior of the transplanted heart upon exertion]. PMID- 3331807 TI - [Hemodynamic response to isometric exercise in patients with a denervated heart]. PMID- 3331809 TI - [Electrophysiologic features of the transplanted heart]. PMID- 3331810 TI - [Renal function in the immediate postoperative period after heart transplantation using very low initial doses of cyclosporin A]. PMID- 3331811 TI - [Coronary vasculitis appearing soon after heart transplantation: diagnosis and treatment]. PMID- 3331812 TI - [Pulmonary function in the heart transplant patient treated with cyclosporin A]. PMID- 3331813 TI - [Infections in the heart transplant patient treated with cyclosporin A]. PMID- 3331814 TI - [Infrastructure and coordination of heart transplantation in Spain (1987)]. PMID- 3331815 TI - [Cardiac lesions in the transplanted heart: clinical relevance of dopamine administered to the donor]. PMID- 3331816 TI - [Heart transplantation at the Marques de Valdecilla Hospital, Santander]. PMID- 3331817 TI - [Heart transplantation. Experience at the Clinica Puerta de Hierro in Madrid]. PMID- 3331818 TI - [Joint clicking in patients with temporomandibular joint dysfunction]. PMID- 3331819 TI - [Comparative study of precision of impression materials. Effect of technic, time, and distance]. PMID- 3331820 TI - [Impression of root canals. Technic using vinyl acetate]. PMID- 3331821 TI - [Oral rehabilitation of perimolysis. Treatment with bonded prosthesis]. PMID- 3331822 TI - [Creation of intra-radicular space with metallic posts]. PMID- 3331823 TI - [Elastic impression materials: clinical suggestions]. PMID- 3331824 TI - [Oral cancer and related factors]. PMID- 3331825 TI - Hip dysplasia and ascorbate therapy: fact or fancy? PMID- 3331826 TI - Canine hip dysplasia: past and present. PMID- 3331827 TI - A Rhode Island philosopher (Elisha Bartlett). By William Osler, 1899. PMID- 3331828 TI - Analysis of human chromosome 11 by somatic cell genetics: reexamination of derivatives of human-hamster cell line J1. AB - Through the fusion of a CHO cell population to a human cell population, a hybrid cell line which has lost all human chromosomes except chromosome 11 was derived. This cell line, J1, does not appear to segregate human chromosome 11 during growth. A series of deletion segregants were isolated from J1 which had lost a portion of either the long, short, or both arms of chromosome 11. This panel of deletion segregants was used for mapping a number of genetic markers on the short arm of chromosome 11. Karyotypic analysis led to the interpretation that derivatives of J1 selected for the loss of cell surface antigens encoded by genes on the short arm of the chromosome had simple terminal deletions of this chromosome arm. More recently, we have applied recombinant DNA and in situ hybridization techniques to the analysis of the structure of chromosome 11. In the course of this analysis, we have obtained data that indicate that all J1 deletion segregants retain a small chromosomal segment containing the structural genes for insulin and HRAS1. Analysis of in situ hybridization data indicates that in cell lines in which a chromosome 11 fragment cannot be identified by karyotype analysis, human DNA has been translocated to a Chinese Hamster chromosome. These results suggest that the original interpretation of the karyotypes of deletion segregants derived from J1 as simple terminal deletions is not correct. A reanalysis of gene localization studies based on these deletion segregants suggests that some assignments of genes to specific bands on chromosome 11 should be reconsidered. In particular, data on additional deletion segregants are consistent with localization of the beta-globin gene complex to band 11p15. The data presented here suggest that in several hybrid derivatives of J1, a continuous DNA segment of approximately 10(7) base pairs in length which includes the insulin and HRAS1 (cellular homolog of retroviral oncogene Harvey ras) genes has been isolated from the remainder of the human genome. We propose that the stability of chromosome 11 in the original hybrid was due to complementation of a genetic defect in the original CHO cell parent by a gene located in close physical proximity to the insulin and HRAS1 genes on chromosome 11. Data are presented which test and support this hypothesis. PMID- 3331829 TI - Polymorphic DNA markers on the human genomic map: signposts for localization of unknown genes. PMID- 3331830 TI - Chromosome microdissection and microcloning in human molecular genetics. PMID- 3331832 TI - Overview of human cells in genetic research: altered phenotypes in human cells caused by transferred genes. PMID- 3331831 TI - Multiple recurrent genomic rearrangements and fragile sites in human cancer. PMID- 3331833 TI - Insertion of dominant selectable markers into the human genome. AB - In the above discussion, I have outlined the current status of our efforts to use retroviral vectors to introduce selectable markers into the human genome and to use these markers for mapping specific chromosomal regions. I have not reviewed in detail the extensive characterization of the mouse H-2 region carried out by David Nelson and John Weis based on the insertion of a single retroviral element. This analysis has provided a model for the application of retroviral elements into various regions of the human genome. The prospects for increasing the resolution of the human genetic map and identifying many genes relevant to human health and development are likely to be enhanced by increasing the precision of this methodology. PMID- 3331834 TI - Progress in understanding mechanisms of the serum cholesterol risk factor in atherosclerosis. PMID- 3331835 TI - Genetics and the future of medicine. PMID- 3331836 TI - Experience with percutaneous transhepatic fiberoptic choledochoscopy for retained stones in the biliary tract. Report on 15 patients. AB - Residual choledochal stones in 11 patients and stones in the intrahepatic bile ducts in 5 patients were successfully removed by the use of the fiberoptic choledochoscope (FCH-6T), introduced percutaneously into the intrahepatic biliary tract. The reasons for the use of percutaneous transhepatic extraction were: (1) unsuccessful endoscopic papillotomy; (2) unsuccessful choledochoscopic removal via the T-tube tract; (3) high surgical risk; (4) the presence of percutaneous transhepatic biliary drainage for acute cholangitis and acute pancreatitis. All stones were extracted through the liver or the papilla of Vater after crushing them. All minor complications such as pain, vomiting, or fever resolved without further therapy. Percutaneous transhepatic choledochoscopy proved safe and effective for the removal of retained choledochal stones and was essential for the treatment of stones in the intrahepatic bile ducts. PMID- 3331837 TI - [Dentin adhesives]. PMID- 3331838 TI - [Pulp reactions]. PMID- 3331839 TI - [Bonding between resin and silane-treated porcelain]. PMID- 3331840 TI - [Seating of removable dental prosthesis with post and core construction in endodontically treated teeth]. PMID- 3331842 TI - [Subperiosteal implants]. PMID- 3331841 TI - [Developments in oral implantology during the recent 25 years]. PMID- 3331843 TI - [Isolation prior to placement of composites--a critical review]. PMID- 3331844 TI - [The retention of 1360 anterior composite bridges]. PMID- 3331845 TI - Vitamin D: is the brain a target? PMID- 3331846 TI - Gas chromatography-mass spectrometry and the measurement of vitamin D metabolites in human serum or plasma. AB - Although methods for the measurement of vitamin D metabolites continue to be developed, few have been properly validated by comparison with methods based on gas chromatography-mass spectrometry, widely accepted as being the definitive methodology. To the best of our knowledge, only three such comparisons have been carried out (14, 42, 83), all three examining HPLC assays for 25-OH-D. This lack of proper validation leads to lack of certainty as to the specificity of many assays widely used for clinical investigation. In our view there is an obvious need for the continuing development of mass fragmentographic assays for vitamin D and its metabolites, primarily for use as reference procedures for the evaluation of less rigorous methodologies. Provided standards, both labeled and unlabeled, become more widely available, development of specific mass fragmentographic assays for any metabolite of vitamin D should be possible. For metabolites where no specific binding protein or antiserum is available, mass fragmentography may be the only alternative. PMID- 3331847 TI - Vitamin D and the immune system. AB - The investigation of the potential influence of 1,25-(OH)2D3 on immune cells has expanded our understanding of hormone-cytokine interactions. 1,25-(OH)2D3 stimulates phenotypic and function changes in immature monocytes, alters protein synthesis, increases adherence, and augments interleukin-1 secretion. T lymphocyte proliferation and B cell immunoglobulin production are inhibited by the hormone. 1,25-(OH)2D3 decreases IL 2 and IFN-gamma synthesis by activated T lymphocytes in association with decreases in mRNA for these proteins. The step from the investigation of in vitro interactions to an understanding of in vivo effects of 1,25-(OH)2D3 on immune cells requires further study. On the basis of information at hand, such as the potential for macrophage conversion of 25-OH-D3 to 1,25-(OH)2D3, decreased or increased macrophage function in association with vitamin D3 status in vitro and in vivo, as well as altered T cell subset ratios and proliferative responses with administration of the hormone, it is tempting to speculate that 1,25-(OH)2D3 exerts an influence on immune cell function in concert with other recognized soluble mediators of monocyte and lymphocyte origin. The primary influence of 1,25-(OH)2D3 may vary with the tissue site. Systemic levels of hormone may aid in maintaining tonic immunosuppression and thus prevent trivial antigenic stimuli from initiating an immune response. Upon initiation of an immune response to a significant antigenic challenge 1,25 (OH)2D3 may, in concert with other suppressor mechanisms, limit the extent of the host response by inhibition of IL 2 and IFN-gamma production. At local sites of chronic inflammation concentrations of 1,25-(OH)2D3 may be elevated and may act in an autocrine or paracrine fashion to alter the immune response, for example, by increasing IL 1 production and antigen presentation by tissue monocyte/macrophages. The activation of T cells is associated with the synthesis of 1,25-(OH)2D3 receptors, thus potentially limiting T cell proliferation in the presence of the hormone. Other biological actions of IL 1, however, including effects on cells in bone, joint, and brain may be augmented. Thus, the end result of the opposing effects of 1,25-(OH)2D3 on immune cells and their secretory products may vary with the specific cells involved, their state of maturation and activation, and the local concentrations of the hormone. Studies to date support the concept of an expanded role for 1,25-(OH)2D3 in immune cell biology. PMID- 3331849 TI - Sex-specific isozymes of cytochrome P-450. PMID- 3331848 TI - The vitamin D-induced differentiation of HL-60 cells: structural requirements. PMID- 3331851 TI - [Post-traumatic bursitis--histological expert assessment and insurance medicine aspects]. AB - Concerning insurance medical reports on posttraumatic bursitis the histological findings hold an important position. 20 operation preparations of bursae with a known trauma have been studied. Thereby criterion for the histological characterization of posttraumatic bursitis have been set up and furthermore the findings have been correlated with the posttraumatic time interval. Sector-like fiber necrosis, defects of the top-cell layer, new erythrocyte extravasations, beginning inflammatory reactions and ensilages of foreign bodies in the histological preparation confirm the results of the medical opinion in the acute stage until 24 hours after the trauma occurred. The traumatic genesis of bursa alternations can be verified up to two weeks after the trauma through defects of the top-cell layer, fiber necrosis in all layers of the bursa wall, and erythrocyte extravasations. Preparations of which the trauma is dated back more than two weeks can be classified as posttraumatic bursitis because of their numerous chronifying processes only by their fiber continuity or by their granulation zone which reaches to the synovial surface. Four weeks after a suitable trauma it becomes more difficult to differentiate definite posttraumatic bursa findings from the morphological presentation of the so-called chronic unspecified polyetiological bursitis. In the late posttraumatic stage the pathologic-anatomical differential diagnosis is only possible with considerable reservations. The clinical data on the course of disease gain particular importance for the insurance medical judgement in such late medical reports. PMID- 3331852 TI - Presidential address. PMID- 3331850 TI - [Microscopic observation of some amalgam adhesion to cavity walls of teeth]. PMID- 3331854 TI - Association of American Physicians. List of members. PMID- 3331853 TI - Presentation of the George M. Kober Medal (posthumously) to Helen B. Taussig. PMID- 3331855 TI - Control elements in the human renin gene. PMID- 3331856 TI - cis-acting DNA sequence controls glucagon gene expression in pancreatic islet cells. AB - Our studies show that cis-acting DNA sequences present in the 5'-flanking region are important for the promotion of glucagon gene transcription in islet cell lines. Deletion of all but 292 bp of 5'-flanking sequences results in no major change in the relative magnitude of transcriptional activity in glucagon producing RIN1056A cells. Moreover, transcriptional activity of the GLUCAT fusion genes is consistently greater in glucagon-producing than in insulin-producing islet cell lines. The cellular specificity of glucagon gene transcription is further emphasized by the lack of transcriptional activity following transfection of non-islet cell lines (BHK, HeLa, and JEG cells) with five different GLUCAT plasmids. These observations suggest that trans-acting factors present in islet cell lines interact with DNA sequences in the 5'-flanking region of the rat glucagon gene to mediate islet cell-specific gene transcription. These studies should provide a useful model for the isolation and characterization of the trans acting factors important for glucagon gene transcription. PMID- 3331857 TI - A prospective study of anti-neutrophil cytoplasm antibodies in systemic vasculitis detected by solid-phase radioimmunoassay. PMID- 3331858 TI - Erythrocyte membrane: structure, function, and pathophysiology. PMID- 3331859 TI - Intestinal Chlamydia in pigs. PMID- 3331860 TI - Immunohistochemical localization of myoglobin in connective tissue tumors in dogs. PMID- 3331861 TI - [Economy circuit of fetal circulation illustrated on the basis of personal quantitative Doppler blood flow parameters]. AB - Percentile curves of the mean blood flow velocity and the mean blood flow volume of the fetal aorta were calculated from a normal study group comprised of 290 pregnant women. Additionally ratios of the mean blood flow velocity or blood flow volume of the fetal common carotid artery and the fetal aorta were established. In a high risk group with a loss of end-diastolic blood flow velocities in the umbilical artery and/or fetal aorta and subsequent primary caesarean section due to fetal distress (pathological CTG) we investigated the course of the above mentioned parameters. The ratio of the mean velocity or the mean blood flow volumes showed and increased in all 10 cases of the high risk group from the first to the last measurement. In all cases the final level before the delivery was far above the 95th centile. The underlying pathophysiological occurrence of the conserving adaptation of the fetal circulation is expressed by the ratios. This is why we consider these parameters to be of great importance in the supervision of high risk pregnancies in the future. PMID- 3331862 TI - [Comparative studies of the venous system of the arm and leg before and after delivery]. AB - Venous occlusion plethysmographic measurements were performed on the legs of ten non-pregnant subjects on ten consecutive days, in order to demonstrate the reproducibility of this method. In the third trimester of gestation and on the seventh day post partum, venous occlusion plethysmographic studies and vein caliber measurements were performed on arms and legs of 20 patients. A significant reduction in leg vein diameter following delivery was found. There were no differences in the diameters of arm veins measured in the third trimester and post partum. The results of venous occlusion plethysmography, as an indicator of venous function, revealed no differences between the third trimester and post partum in either the arm or the leg. Since hormonal changes during gestation must affect the entire venous system, i.e., also the arms and legs, mechanical displacement of the blood drainage pathways by the gravid uterus is most probably responsible for the significant dilatation of leg veins in the third trimester. A displacement of the higher sections of the femoral vein was demonstrated by Doppler sonography. Increased distensibility of the veins in the third trimester, continuing post partum, is probably the measurable basis of the much higher incidence of varicosis among women who have had children. It appears possible to detect extreme dilatations of leg veins sonographically, and to counter the increased risk of thrombosis and perhaps also to reduce the risk of later varicosis by timely compression treatment. PMID- 3331864 TI - [Chorioangioma--sonographic diagnosis and clinical significance]. AB - This paper presents two cases of large placental chorioangiomas associated with polyhydramnios, detected in the 25th and 27th week of pregnancy, respectively, using ultrasound. The tumors produced complex echo-pattern with transonic and echogenic areas. In the one case, the fetus, malformed by an omphalocele, was spontaneously aborted in the 25th week. In the other case, regular contractions, resistant to any therapy, and fetal asphyxia urged delivery by Caesarean section in the 27th week. The neonate died from pulmonal prematurity. The reported complications associated with large chorioangiomas and perinatal mortality up to 80%, according to the literature, underline the need for early sonographic diagnosis. PMID- 3331865 TI - [15 years of experimental and clinical implantology in the Gottinger clinic: development status and present position]. PMID- 3331863 TI - [Obstetrical analgesia with tramadol--results of a prospective randomized comparative study with pethidine]. AB - Morphine derivatives are the most frequently used analgetic substances in obstetrics today. Nevertheless, nausea, vomiting, weariness, and somnolence are common side effects of these drugs. Moreover opiates exhibit a depressive effect on ventilatory activity. As many studies have demonstrated tramadol, a new analgetic substance amongst the opiates does not show a depressive effect to such a high degree. In this prospective randomized trial we compared the efficacy as well as the safety of 100 mg tramadol and 100 mg pethidine in 40 women asking for pain relief during labour. The duration of labour was slightly but not statistical significantly shorter in the pethidine group. An analgetic effect could be observed in the pethidine as well as the tramadol group by both the pregnant women and the attending physician about 10 min after application lasting for about 2 hours. Concerning the side effects tramadol highly contrasted with pethidine. There were less cases of weariness and somnolence and the ventilatory frequency of the newborn babies tended to be higher than in the pethidine group. The serum levels of tramadol in umbilical and maternal veins demonstrated values of 0.83 +/- 0.15 (mean +/- SEM; quotient). The results of this study seem to establish an analgetic effect of tramadol similar to pethidine but with less side effects. PMID- 3331866 TI - [Ascher's contribution to the development of orthodontic diagnosis and therapy]. PMID- 3331867 TI - [Question of functionality of tooth set-up for complete denture by guide plane criteria]. PMID- 3331868 TI - [Preoperative diagnosis in dental implantology]. PMID- 3331869 TI - [Complete denture--question of remounting]. PMID- 3331870 TI - [Prosthetic case: double clasp-crown-bridge]. PMID- 3331871 TI - [American dentists in Germany (1880-1920)]. PMID- 3331872 TI - [Acid etch technique in prosthetic crown and bridge work]. PMID- 3331873 TI - [Influence of casting procedure upon surface-roughness of gold-alloy-castings]. PMID- 3331874 TI - Research methodology series. Computerized bibliographic databases. PMID- 3331875 TI - Quantitatively reviewing the literature: the application of meta-analysis. AB - Meta-analysis has evolved as an alternative to the conventional narrative review. Its purpose is to statistically analyze a large collection of results from multiple studies in order to integrate the findings. There are three basic components of meta-analytic methodology. Inclusiveness involves the location of studies and decisions regarding which studies to include in the analysis. Quantification refers to the expression of such outcomes as effect sizes and the coding of study characteristics. Integrating outcomes involves the pooling of results from individual studies. Critics of meta-analysis have focused on aspects of the methodology, but careful meta-analytic procedure protects against most potential biases. The methodological and statistical rigor of meta-analysis pressures us to conceptualize our research more clearly and report results more completely. PMID- 3331876 TI - Prenatal diagnosis of genitourinary tract malformations. AB - Ninety cases of genitourinary tract anomalies diagnosed before birth are reviewed. Factors stressed are the relationship between the site of the anomaly and the time of the diagnosis. Low level urinary tract obstructions tend to be diagnosed early, high level lesions late. Overall, the diagnostic accuracy was 88% with urethral obstruction being most often accurately diagnosed (19 of 20 cases). The frequency with which associated anomalies are found is stressed as is the lack of correlation between amniotic fluid volume and high or mid level obstructions. Ovarian cysts are usually diagnosed late in gestation and are seldom associated with other anomalies. PMID- 3331877 TI - Biometric diagnosis of intrauterine growth retardation. AB - The history of the use of ultrasound for the detection of abnormal fetal growth is briefly reviewed. The problems associated with the two most commonly used parameters (biparietal diameter and abdominal circumference) are briefly reviewed. These problems are often compounded by uncertainty surrounding the gestational age. The many other parameters that have been used to assess fetal growth are briefly reviewed. A prospective study utilized two ultrasound examinations: the first at 16-20 weeks predicted the correct estimated date of confinement and the second at 32-34 weeks reliably demonstrated intrauterine growth retardation. The need for further clinical trials is stressed. PMID- 3331878 TI - Management of intrauterine growth retardation: diagnostic and clinical aspects. AB - A retrospective analysis of the ultrasonic charts of 150 pregnancies with a birth weight below the tenth percentile is presented. In all cases the first scan was carried out before the 20th week of gestation to assess gestational age measuring crown to rump length or biparietal diameter (BPD). Subsequent scans every 4 weeks measured BPD or abdominal circumference. Birth weight was below the fifth percentile in 70 cases and between the fifth and tenth percentiles in 80 cases. A risk condition was found in 32.26%. The first observation of an abnormal parameter was widely spread throughout the latter half of the pregnancy. The management of IUGR included close observation and often required planned delivery. Cesarean section was required in 30.75% of the cases. Acute fetal distress has been the indication in 17.6% of cases and chronic fetal distress in 41.3%. Perinatal mortality was 6.66%. The need for criteria that will accurately detect the fetus most at risk from complications of IUGR is stressed. PMID- 3331879 TI - Pregnancy outcome following ultrasound diagnosis of fetal urinary tract anomalies and/or oligohydramnios. AB - We have reviewed 49 pregnancies with ultrasound evidence of fetal urinary tract anomalies and/or oligohydramnios. A surprisingly large number of fetuses with urinary tract obstruction had significant other anomalies. Fetuses with urinary tract obstruction, but a normal amount of amniotic fluid, did well without in utero intervention; however, those with oligohydramnios or polyhydramnios fared poorly. Longer periods of oligohydramnios in fetuses with urinary tract obstruction seemed to be associated with pulmonary hypoplasia and renal dysplasia. Oligohydramnios without urinary tract obstruction complicated 28 pregnancies; there were only 10 survivors. Diagnostic pitfalls are described. PMID- 3331880 TI - Is the intrauterine treatment of fetal hydrocephalus helpful or harmful? AB - An assessment of the current status of intrauterine treatment of fetal hydrocephalus is presented. An attempt is made to evaluate the outcome of clinical trials reported to the International Registry of Fetal Treatment. Future developments, based on the outcome of experiments with animal models, are discussed. PMID- 3331882 TI - The rapid, hormonally stimulated transport of calcium (transcaltachia) PMID- 3331881 TI - Primates and anencephalics as sources for pediatric organ transplants. Medical, legal, and ethical issues. AB - This article discusses some of the medical, legal, and ethical issues in using organs from primates and anencephalics to transplant to infants who will otherwise die. The use of primates is discouraging on ethical grounds due to scarcity of chimpanzees, the preferred species, and to the poor chance of survival. Anencephalic fetuses and newborns are promising sources of organs for pediatric transplants, provided that ethical and legal considerations are met. An argument is made, based on current practice in management of dying donors, that complies with the legal requirement to delay organ removal until after whole brain death; however, this approach requires the compensating step of gradual cooling of the body of the newly delivered anencephalic to save the organs from ischemia. PMID- 3331883 TI - A tissue-specific protein in rat osteogenic tissues. AB - A tissue-specific protein fraction has been detected in rat osteogenic tissue. Dissociative extraction of adult rat bone matrix with 4 M guanidinium chloride solution was followed sequentially by gel chromatography and polyacrylamide gel electrophoresis. By the latter procedure a prominent protein component of molecular weight 19,000 was isolated from the low molecular weight fraction, and antibodies directed against this protein were raised in rabbits. The antibodies were mainly against antigenic sites on this protein, as shown by protein blotting techniques. By embedding rat tissues in hydrophilic plastic and by using immunohistochemical procedures the presence of this protein was demonstrated specifically in bone matrix in vivo, in osteogenic tissue developing in diffusion chamber culture, and in a malignant osteoblast cell line (UMR 106). Soft tissues (liver, kidney, spleen, gut, skin, thymus, eye) showed no reactivity with the antiserum and in vitro a further malignant osteoblast cell line (ROS 17/2.8) did not synthesize the 19,000 molecular weight protein. This protein appears to be expressed solely by osteogenic tissue and may be used as a biochemical criterion of osteogenic differentiation. PMID- 3331884 TI - [History]. PMID- 3331885 TI - [The Branemark System]. PMID- 3331886 TI - [Artificial biointegrated roots with tricortical support. Diskimplants]. PMID- 3331887 TI - [The IMZ implants of Kirsch]. PMID- 3331888 TI - [The stabilized blade implant]. PMID- 3331889 TI - [Deoxidant agent in casting investments]. PMID- 3331890 TI - [A clinical re-evaluation of an Hinoporon on periodontal disease using the double blind method]. PMID- 3331891 TI - [Evaluation of alloy-composite resin adhesive strength of Silicoater System]. PMID- 3331892 TI - [Histopathological changes of the rat periodontal tissues caused by application of bacterial protease]. PMID- 3331893 TI - [Zinc nutrition in young Chilean adults]. AB - To evaluate the effect of dietary factors on plasma zinc levels, dietary zinc intake was estimated and plasma levels were measured in 37 healthy young adults of low and middle socioeconomic status. Our study included 16 males aged 29 +/- 7 and 21 females aged 26 +/- 6 years. Dietary intake of zinc and protein was determined from a 24-hour dietary recall survey. Plasma zinc was measured by atomic absorption spectrophotometry. Alkaline phosphatase (AP) in plasma was also measured and the weight/height percentage for each subject calculated according to Jelliffe's standards. The average diet was composed of cereals, legumes, eggs, bread and noodles, caloric intake was 2051 +/- 154 kcal/day for men and 1767 +/- 158 (x +/- SD) kcal/day for women. The daily intake of zinc was 8.3 +/- 3.0 mg/day for males, and 9.7 +/- 2.0 mg/day for females. Cereals were the main source of zinc for men, while egg and dairy products were for women. Plasma zinc values were 82 +/- 22 micrograms/dl for men and 94 +/- 19 micrograms/dl for women (p less than 0.01). For the whole group plasma zinc concentration was 89 +/- 21 micrograms/dl. Seven males and two females had low plasma zinc values (70 micrograms/dl or less). Alkaline phosphatase (AP) levels were 110 +/- 10 IU for males and 71 +/- 4 IU for females (p less than 0.001). These values did not correlate with the zinc levels. Average weight/height was 99 +/- 18 for men, and 108 +/- 18 for females. Results indicate that on the average, in our study group plasma zinc levels were within the normal range, although they were significantly lower in men. Dietary intake of zinc was below the recommendations, being higher for women as related to values presented by men. The observed low plasma levels of zinc may be caused by a low intake, and/or poor bioavailability. PMID- 3331894 TI - [Lichen planus of the oral cavity: possible malignant transformation]. PMID- 3331895 TI - [New diagnostic methods for research on Candida albicans]. PMID- 3331896 TI - History of ptosis surgery. PMID- 3331897 TI - The history of lacrimal surgery. PMID- 3331898 TI - The development of ophthalmic plastic surgery. PMID- 3331899 TI - Fractures of the orbit and injuries to the eye in war by Felix Lagrange. From Fractures of the Orbit, 1918. Translation. PMID- 3331900 TI - The evolution of ophthalmic sutures [classic article]. PMID- 3331901 TI - History and development of ophthalmic plastic and reconstructive surgery in Italy. PMID- 3331902 TI - A history of oculoplastic surgery in Spain. PMID- 3331903 TI - History and development of ophthalmic plastic and reconstructive surgery in Germany and Austria. PMID- 3331905 TI - The history and development of lacrimal surgery in England and Europe. PMID- 3331906 TI - Ophthalmic plastic and reconstructive surgery in the United States: 1893-1970. PMID- 3331904 TI - History of ophthalmic plastic surgery in Europe. PMID- 3331907 TI - Reconstructive surgery of the eyelids. PMID- 3331908 TI - The New York Eye and Ear Infirmary oculoplastic surgery: where it all began. PMID- 3331910 TI - The history and development of ophthalmic plastic surgery at MEETH. PMID- 3331909 TI - The history of the Oculoplastic Department of Wills Eye Hospital. PMID- 3331911 TI - Ophthalmic plastic and reconstructive surgery at the Manhattan Eye, Ear and Throat Hospital. PMID- 3331912 TI - Oculoplastics at Bellevue. PMID- 3331913 TI - The Edwards S. Harkness Eye Institute. PMID- 3331914 TI - John Martin Wheeler. Biographical sketch. PMID- 3331915 TI - The origins of ophthalmic plastic surgery at Yale. PMID- 3331916 TI - Edmund Benjamin Spaeth. PMID- 3331917 TI - The development of oculoplastic surgery in the West. PMID- 3331918 TI - The development of oculoplastic surgery: a view from the wings. PMID- 3331919 TI - John Marquis Converse, MD as I knew him. PMID- 3331921 TI - The history and development of ophthalmic plastic and reconstructive surgery in Canada. PMID- 3331920 TI - Micrographic surgery for the microscopically controlled excision of eyelid cancer: history and development. AB - The development of a method for the total microscopic control of excising external cancer began with the concept of first excising the affected tissues in successive layers and then using frozen sections for the systematic microscopic scanning of the entire undersurface of each layer. This method permitted the precise detection and selective removal of "silent" cancerous ramifications and obviated the need to sacrifice a margin of normal-appearing tissue. The reliability of the method for treating eyelid cancers is manifested by high 5 year cure rates of 98% for basal cell carcinoma and 98.1% for squamous cell carcinoma. The maximal conservation of normal tissues simplifies any needed repairs and permits some innovative ways of managing wounds with healing by granulation and by partial closures with guiding sutures. PMID- 3331922 TI - Development of oculoplastic surgery in Australia. PMID- 3331924 TI - History of the founding of the ASOPRS. PMID- 3331923 TI - Radiology in ophthalmic plastic surgery: a brief history. PMID- 3331925 TI - The Byron Smith Study Club. PMID- 3331926 TI - Ophthalmic plastic surgery from 3000 BC to 1000 AD. PMID- 3331927 TI - The history of cosmetic blepharoplasty. PMID- 3331928 TI - History of surgery for involutional ectropion. PMID- 3331929 TI - Treatment of ocular complications. By Felix Lagrange, 1918. PMID- 3331930 TI - The ocular sequelae of blunt trauma. AB - Blunt trauma can cause a wide range of ocular injuries. An immediate evaluation of the potential damage may be impossible because of vitreous hemorrhage or may be ill-advised because of hyphema or damage to other ocular or orbital structures. One must remember that potentially severe injuries can be harbored in the recesses of the angle or far periphery of the retina. In any case of blunt trauma, although one eye may have more obvious signs of injury, an extensive examination of the fellow eye must always be included because less severe trauma may have resulted in serious injuries that can go undetected. The types of injuries from blunt trauma that threaten vision--damage to the angle, lens, macula, and peripheral retina--must be noted and recorded because all have potential long-term visual consequences. Early treatment of these lesions, especially retinal tears and elevated intraocular pressure, can help prevent potentially severe loss of vision. PMID- 3331931 TI - Posterior segment manifestations of orbital trauma. AB - The posterior segment of the eye can be affected by blunt orbital trauma by either direct or indirect mechanisms or by equatorial expansion. Commotio retinae can occur either at the site of direct or indirect injury. Retinal detachments can be precipitated at the site of the direct injury by a necrotic tear, at the site of the indirect injury with a macular hole, or just posterior to the vitreous base if equatorial expansion plays a role. Contusion effects on the choroid can manifest as a localized hemorrhage, a hemorrhagic choroidal detachment, or a choroidal rupture. Chorioretinitis sclopetaria results from simultaneous laceration of both the retina and choroid due to the shock waves from a high-velocity missile passing adjacent to the globe in the orbit. PMID- 3331932 TI - Pathogenesis of fractures of the orbit. By Felix Lagrange, 1918. PMID- 3331933 TI - Fractures of the orbit with preservation of the eyeball. By Felix Lagrange, 1918. PMID- 3331934 TI - The radiology of orbital trauma: an historical overview. AB - Professor Roentgen presented the roentgen ray in 1895. The subsequent history of radiology is characterized not by steady, but by stepwise advancement. Each new innovation produced a forward surge followed by a period of refinement in which the new method was developed and exploited to the very limits of its diagnostic yield. PMID- 3331935 TI - The discovery of blowout fractures of the orbit. PMID- 3331936 TI - Blowout fracture of the orbit: mechanism and correction of internal orbital fracture. By Byron Smith and William F. Regan, Jr. PMID- 3331937 TI - Advanced diagnostic imaging techniques in ophthalmology. AB - Diagnostic imaging techniques continue to gain tremendous importance in the evaluation of ocular and orbital disease as technical developments and refinements are made. This article presents key diagnostic imaging methods, with special focus directed toward the advanced modalities important in evaluation of the traumatized eye and orbit. The text has been prepared specifically for the clinical ophthalmologist. Each of the diagnostic modalities discussed is presented in terms of its basic biophysical mechanism, indications, and advantages and disadvantages. The techniques described include simple plain film roentgenography (and its contrast-related applications: dacryocystography, orbital venography, and angiography), axial hypocycloidal tomography, computed tomography, ultrasonography, and magnetic resonance imaging. PMID- 3331938 TI - Injuries and diseases of the orbit. Traumatic enophthalmos with retention of perfect acuity of vision. By William Lang, 1889. PMID- 3331939 TI - Traumatic enophthalmos. By Raymond L. Pfeiffer, 1943. PMID- 3331940 TI - Sequelae of orbital fractures. AB - Many injuries and complications of orbital fractures are instantaneous and unpreventable, some develop over time, and some are a result of surgery. Most complications can either be managed or prevented and are anticipated based on the fracture location and size. A thorough search for probable complications is mandatory, especially ocular injuries and intracranial complications. Most patients are carefully followed for 7-14 days, and the significant residual sequelae are managed. Some complications, however, require urgent care. PMID- 3331941 TI - Treatment of fractures of the orbit and their complications. By Felix Lagrange, 1918. PMID- 3331942 TI - Reparative surgery of orbital fractures. By Felix Lagrange, 1918. PMID- 3331943 TI - Trimalar fractures: diagnosis and treatment. AB - Trimalar fractures of the zygoma are not infrequent midfacial injuries and are a distinct clinical entity. Specific clinical findings include infraorbital anesthesia, trismus, diplopia, enophthalmos, palpable bony suture line abnormalities, flattened malar eminences, and superior sulcus deformities. Six radiologic subgroups have been described. Optimal surgical management and treatment depend on the type of fracture. Three general surgical approaches are currently used: the Gillies technique, the supraorbital approach, and the maxillary sinus approach. PMID- 3331944 TI - Orbital compartment syndromes following trauma. AB - The etiology of traumatic optic neuropathy is uncertain, except when intraocular pressure is elevated and CRAO can be observed. Various mechanisms have been implicated, and the etiology probably varies with individual cases. Prognosis is best when vision is initially intact and subsequently deteriorates, suggesting compression that may be reversible. Some authorities recommend high doses of systemic steroids as initial therapy. Anatomically, the orbit is a relatively closed compartment, and significant pressure may develop following intraorbital hemorrhage, edema, or emphysema. When clinical signs of severe orbital hemorrhage and pressure (proptosis) are associated with an optic neuropathy, the clinician is faced with a difficult decision. Mechanical decompression of the orbit is technically within our ability, and considerable positive experience has been derived from the treatment of compressive optic neuropathy in Grave's disease. Although the efficacy of decompression in trauma is uncertain, the literature provides anecdotal reports of restored vision. With full informed consent regarding these issues, orbital decompression seems appropriate for the rare case in which clinical signs of orbital pressure are impressive. PMID- 3331945 TI - Optic nerve evulsion and transection. AB - Injury to the optic nerve may occur after seemingly minor trauma. Evulsion of the nerve from the globe may be partial or complete as a result of several concussive or rotational forces. A depressed or visibly absent lamina cribrosa indicates a disinsertion of the nerve fibers from the globe. Visual loss ranges from severe to complete. Transections of the optic nerve within the orbit generally occur after penetrating orbital injuries or surgical resection, resulting in complete blindness. Medical or surgical intervention has not been shown to improve the visual prognosis once such injuries occur. The etiology, clinical features, and histopathology are also discussed. PMID- 3331946 TI - The orbital cavity. Its conformation, its protective role, its resistance to traumatism, its vulnerability. By Felix Lagrange, 1918. PMID- 3331947 TI - Diagnosis and management of traumatic optic neuropathies. AB - If a patient has vision immediately following trauma, with subsequent deterioration of visual acuity and/or field, and the presence of a relative afferent pupillary defect, compression of the optic nerve or its vascular supply is very likely. We currently lack a proven optimal treatment, but in the otherwise healthy patient, we suggest an intravenous (IV) loading dose of methylprednisolone 30 mg/kg, and a second 15-mg/kg dose 2 hours after the initial dose, followed by 15 mg/kg every 6 hours. Optic nerve decompression is indicated in this situation when corticosteroids have only a temporary effect, a diminishing one, or none at all. It may also be indicated when there is evidence of a traumatic optic neuropathy with a fractured or narrowed optic foramen or with dislocated bone fragments that directly impinge on the nerve. Optic nerve sheath decompression is indicated in progressive traumatic optic neuropathy when an enlarged fluid-filled sheath has been demonstrated sonographically. PMID- 3331948 TI - Double valve disease in systemic lupus erythematosus. Case report and literature review. AB - A young, nonhypertensive female with advanced systemic lupus erythematosus (SLE) presented in congestive cardiac failure due to aortic and mitral regurgitation. The valvular lesions resulted from organization of valvular pocket Libman-Sacks vegetations. Her clinical course mimicked infective endocarditis. She is only the third recorded patient with SLE valvular disease warranting double valve replacement. This patient, who had her valvular disease at presentation (prior to initiation of steroid therapy), illustrates that untreated SLE per se may produce severe organic valvular disease. PMID- 3331949 TI - Granulocytes as active participants in acute myocardial ischemia and infarction. AB - The classical picture of the polymorphonuclear leukocyte--antimicrobal activities and participation in the inflammatory reaction--appears now to be expanded. It has been recognized that this cell may be highly injurious to other cells, has a propensity to be trapped in the capillary network, and may occlude microvascular pathways. The classical hypothesis that the granulocytes appear in the ischemic or postischemic myocardium as response to the associated inflammatory reaction may have to be revised. Instead, the granulocyte may actually be the key factor causing the inflammation. An array of future studies is needed to clarify the events step by step. Important aspects are the activation and degranulation sequence in the ischemic myocardium, the form and extent of injury caused by the oxygen free radicals and lysosomal enzymes, the source and nature of chemotactic substances, particularly in human forms of myocardial ischemia, and the degree to which granulocytes cause or magnify the injury. PMID- 3331950 TI - Myocardial lymphocytes. Fact, fancy, or myocarditis? AB - The diagnosis of active lymphocytic myocarditis by the use of the endomyocardial bioptome is at present a hotly debated topic. However, the question of whether lymphocytes reside in the myocardium of individuals without systemic or cardiac disease has rarely been addressed, but is obviously of critical importance in helping to resolve this issue. Therefore, we examined endomyocardial biopsies obtained from 86 young heart disease-free cardiac transplant donors at the time of transplantation. Foci of inflammatory cells were found in eight (9.3%) cases and by definition contained greater than five inflammatory cells per focus. The inflammatory infiltrates were predominantly lymphocytic. Based on these results and those of others, it is becoming evident that there is a normal myocardial lymphocyte population which must be reckoned with when considering the diagnosis of myocarditis, realizing the potential therapeutic implications of this diagnosis. PMID- 3331951 TI - Mental duality in the intact brain. AB - It has been a signal honor to be president of the Los Angeles Society of Neurology and Psychiatry, which supported for 50 years a forum (the Bulletin of the Los Angeles Neurological Societies) for other than routine views, including those of its famous founders. One of these was Dr. J. M. Nielsen. I remember one of his brain cuttings relevant to this paper: After someone had read the history, he said, "Let's look at the anterior commissure." He held the brain with one hand and that big knife in the other (as you know, the anterior commissure is shaped like a handlebar mustache) and he made one curving sweep through the brain; then he lifted off the top half, and there was the full extent of the commissure. Another Founder, Dr. Cyril Courville taught me as a neurology resident for a year, followed by my time with Dr. Philip Vogel, whose skill and intestinal fortitude resurrected cerebral commissurotomy (1). Dr. Courville, as Editor of the Bulletin, was succeeded by Dr. Clarence Olsen who was succeeded in the Bulletin's 30th year by Dr. Richard Walter. This paper is an extension, to some extent, of my articles called The Other Side of the Brain which were published in the Bulletin in 1969 (2-4). Those articles presented ideas some of which may now seem fairly orthodox. But in those days they were not, and I think that Dr. Walter's publishing them was a tribute to his wry sense of humor, as well as his historical perspective. PMID- 3331953 TI - Modulation of antibody response to sheep red blood cells by cyclophosphamide in Calomys callosus (Rodentia). AB - 1. Calomys callosus, a wild rodent reservoir of Trypanosoma cruzi, notably resistant to laboratory infection with this parasite, is currently under study as a new experimental model for Chagas' disease. 2. To investigate the humoral immune response of C. callosus, rodents were injected with sheep red blood cells (SRBC) and the resulting antibody titers measured 0, 5, 9, 14, 20, 27 and 37 days later by the direct agglutination test. 3. Modulation of the antibody response by cyclophosphamide (Cy) was also studied, showing that the administration of 400 or 200 mg Cy/kg body weight one day prior to SRBC inoculation had an immunosuppressive effect. When the 200 mg/kg dose was given on day 0, antibody levels were significantly lower than those of controls on the 5th day after SRBC inoculation; subsequent differences were not statistically significant. 4. When SRBC were injected 5 or 10 days after Cy administration, the same effect was observed, indicating that the time of antigen inoculation is important in antibody modulation. A second dose of 200 mg Cy/kg on day 5 resulted in significant antibody suppression up to the 37th day. The administration of 20 mg Cy/kg resulted in a slight antibody enhancement seen on the 5th day after SRBC inoculation given on day 0. 5. These data demonstrate that cyclophosphamide modulates the T-dependent antibody response in C. callosus in a manner similar to the mouse model. PMID- 3331954 TI - Effect of hydrogen peroxide on Escherichia coli radC. AB - High sensitivity to ionizing radiation is observed in Escherichia coli radC mutants. This is not seen for H2O2-treated cells but when the polA mutation is also present, cells are more sensitive than in the presence of the recA mutation. An increase in inactivation was observed for strains tested when cells are grown in minimal medium and starvation-induced resistance is observed in H2O2-treated cells. PMID- 3331955 TI - Chloramphenicol pretreatment enhances resistance to UV, X-rays and H2O2 damage in Escherichia coli but not of infecting UV-damaged phages. AB - Chloramphenicol pretreatment of Escherichia coli increases resistance to UV, X rays and H2O2 damage. Increased survival of UV-irradiated, infecting lambda phages is not observed. The hypothesis that enhanced survival of chloramphenicol pretreated cells is due to the induction of plasmid "repairons" is questioned. PMID- 3331956 TI - [Evaluation of the effect of Scotchbond and three other dentin adhesives on microleakage]. PMID- 3331952 TI - From lysosomes to cells, from cells to Leishmania: amino acid esters as potential chemotherapeutic agents. AB - Amino acid esters can disrupt lysosomes and damage monocytes and certain lymphocyte populations. Lysosomal disruption involves pH trapping of the esters, followed by their hydrolysis by as yet unidentified enzymes. Accumulation of the more polar amino acids is assumed to cause osmotic lysis of the organelles. We have discovered that certain amino acid esters and amides destroy Leishmania mexicana amazonensis amastigotes lodged within macrophages in culture, as well as parasites isolated from mouse lesions. This paper reviews the amino acid specificity of parasite killing, the resistance of amastigotes derived from infection of macrophages with promastigotes, the involvement of an acidified compartment within the parasites, and the protection conferred by other amino acid esters, and by the protease inhibitors antipain and chymostatin, against the destruction of amastigotes by Leucine-methyl ester. Studies with tritiated esters confirm the critical role of ester hydrolysis for leishmanicidal activity and strengthen the view that similar mechanisms underlie disruption of lysosomes and destruction of Leishmania. Characterization of the parasite organelles and of the enzymes involved in the leishmanicidal activity as well as structure-activity studies may permit the design of compounds more selective for the parasites. PMID- 3331958 TI - The ultrasonic appearance of hepatic hemangioma. PMID- 3331957 TI - [Bacterial contamination from high speed water spray at Chang Gung Memorial Hospital Taipei and Linkou Dental Departments]. PMID- 3331959 TI - [Renal carcinoma and renal cysts in a patient with end-stage renal disease--a case report]. PMID- 3331960 TI - [The significance of "target sign" sonography of gastrointestinal tract in pediatric patient]. PMID- 3331961 TI - [Adult polycystic kidneys associated with transitional cell carcinoma--a case report]. PMID- 3331962 TI - Endoscopic laser or pure alcohol hemostasis for upper gastrointestinal hemorrhage. PMID- 3331964 TI - Ruptured achilles tendon--a case report and literature review. PMID- 3331963 TI - HLA-mismatched allogeneic bone marrow transplantation. PMID- 3331965 TI - Sonography of appendical abscess. PMID- 3331966 TI - [The clinical use of peroneal flap for skin defect in the lower extremity]. PMID- 3331967 TI - The amniotic band syndrome. Report of two autopsy cases and review of literature. PMID- 3331968 TI - Bowenoid papulosis of the vulva--a report of three cases with a review of the literature. PMID- 3331969 TI - Ability of the electrocardiogram to detect myocardial lesions in isoproterenol induced rat cardiomyopathy. AB - Resting electrocardiograms were recorded in 18 male adult rats injected subcutaneously with two doses of isoproterenol (200 mg.kg-1 body weight) 10 days before the animals were submitted to the ajmaline test (1 mg.kg-1 body weight iv). After the ajmaline test all rats were killed and the hearts examined histologically. Electrocardiographic changes were detected at rest in 72% of the isoproterenol injected rats: pathological Q waves, lengthening of the QRS complex, and QRS abnormality were found in 50%, 44%, and 44% of these animals respectively. Ajmaline induced similar changes in both control and isoproterenol treated rats (P wave enlargement (p less than 0.01 and p less than 0.001 respectively), increased PR interval (p less than 0.003 and p less than 0.001 respectively), and increased QaT interval (p less than 0.001 in both groups]. However, ajmaline caused an increase in heart rate only in isoproterenol treated rats (p less than 0.05). A pronounced increase in PR interval, not observed in control rats, was detected in one of five isoproterenol injected rats with a normal resting ECG but showing microscopical cardiac lesions. Apical aneurysm of the left ventricle was found in 16% of isoproterenol injected rats. A mononuclear inflammatory reaction was observed in 13 (72%) of the isoproterenol injected rats and was multifocal in at least three regions of the myocardium in six (46%) and disseminated throughout the myocardium in seven (53%) of these animals. When the electrocardiographic and pathological findings were compared, the ECG changes were found to have a 91% sensitivity, 83% specificity, and 91% positive predictive value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331970 TI - History of implants. PMID- 3331971 TI - Dental implant research. PMID- 3331972 TI - Implants: Evaluation and treatment planning. PMID- 3331973 TI - The implant decision. PMID- 3331975 TI - Implants: Occlusal and prosthetic considerations. PMID- 3331976 TI - Implants: Systemic influences. PMID- 3331974 TI - Implants: Bone physiology and metabolism. PMID- 3331977 TI - Growth hormone responses to pyridostigmine in normal adults and in normal and short children. AB - There is evidence indicating that the cholinergic system positively modulates GH release probably by inhibiting somatostatinergic tone. In the present study, the effects of cholinergic enhancement by pyridostigmine, (PD), a cholinesterases inhibitor, on GH release in normal adults (n = 14) (NA) and in both normal (n = 5) (NC) and short children (n = 19) (SC) with familial short stature (n = 7) or constitutional growth delay (n = 12) were studied. In SC the insulin hypoglycaemia (IH)-induced GH increase was also studied. In both NC and SC 60 mg orally PD induced a significant GH increase with mean peak at 90 min (mean +/- SEM 11.0 +/- 2.2 ng/ml in NC and 11.2 +/- 2.3 ng/ml in SC). The GH areas under response curve (AUC) were 379.3 +/- 76.6 and 327.8 +/- 43.2 ng/ml/h in NC and SC respectively. In NA 120 mg orally PD induced a significant GH increase with mean peak at 120 min (5.1 +/- 1.1 ng/ml) which was significantly lower (P less than 0.05) than that observed in both NC and SC. This statistical difference was strengthened by evaluating AUC (NA:205.6 +/- 33.7 ng/ml/h, P less than 0.05 vs NC and SC). The correlation of drug dosage with body area ruled out that this difference could be related to the different PD dose in adults and children. In SC, IH induced a GH increase significantly lower than that observed after PD (GH peak 7.8 +/- 0.6 vs 16.4 +/- 1.9 ng/ml P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3331978 TI - [Archiater--an honorary title and its bearers]. PMID- 3331979 TI - ["Children the world over" in antiquity]. PMID- 3331980 TI - [Prematurity and malformation]. PMID- 3331981 TI - [Problems of prematurity here and elsewhere]. PMID- 3331982 TI - [Systemic consequences of prematurity]. PMID- 3331983 TI - [The feeding of premature infants]. PMID- 3331984 TI - [Rickets of prematurity and its prevention]. PMID- 3331985 TI - [The infective susceptibility of prematurity]. PMID- 3331986 TI - [The development of premature infants--recollections of Arvo Ylppo]. PMID- 3331988 TI - [Surgical therapy of anterior luxation of the meniscus. 1]. PMID- 3331987 TI - [Periodontal disease: current trends]. PMID- 3331989 TI - [Apically repositioned flap. Clinical results]. PMID- 3331990 TI - [Changes in margins of gold alloy crowns]. PMID- 3331991 TI - [The computer and scientific research in a dental setting]. PMID- 3331993 TI - [A prosthesis for the severe loss of maxillofacial substance. 3. Principles of treatment]. PMID- 3331992 TI - [Surgical therapy of anterior luxation of the meniscus. 2]. PMID- 3331994 TI - [Neurilemmomas of the oral cavity]. PMID- 3331995 TI - [Dentin adhesives]. PMID- 3331996 TI - [Proposal for improved stabilization of a post for multirooted teeth]. PMID- 3331997 TI - Evaluation of aorto-iliac occlusive disease by intravenous digital subtraction angiography. PMID- 3331998 TI - Effects of surgically implanting thermoluminescent dosimeters in small mammals. PMID- 3331999 TI - Historical perspectives on selected health and safety aspects of nuclear weapons testing. AB - This paper presents a general review of public safety standards as adapted by the nuclear weapons testing program in the United States, and the impact of these changing standards on the nuclear testing program itself. The review notes the importance of improvements in diagnostic instrumentation and methodologies from a relatively simple degree of sophistication to their current high level. Use of the improved methodologies uncovered a serious oversight affecting human exposure, namely, that of not recognizing the relative importance of all potential transport/dosimetric pathways for risk assessment. The testing program, from its inception in the Pacific in 1946 to the present time in Nevada, is viewed from the perspective of providing improved radiation protection to the general public. PMID- 3332000 TI - Historical estimates of external gamma exposure and collective external gamma exposure from testing at the Nevada Test Site. I. Test series through HARDTACK II, 1958. AB - In 1959, the Test Manager's Committee to Establish Fallout Doses calculated estimated external gamma exposure at populated locations based upon measurements of external gamma-exposure rate. Using these calculations and estimates of population, we have tabulated the collective estimated external gamma exposures for communities within established fallout patterns. The total collective estimated external gamma exposure is 85,000 person-R. The greatest collective exposures occurred in three general areas: Saint George, UT; Ely, NV; and Las Vegas, NV. Three events, HARRY (19 May 1953), BEE (22 March 1955), and SMOKY (31 August 1957), accounted for more than half the total collective estimated external gamma exposure. The bases of the calculational models for external gamma exposure of "infinite exposure," "estimated exposure," and "1-yr effective biological exposure" are explained. PMID- 3332001 TI - [Clinical factors associated with endodontic dowels]. PMID- 3332003 TI - International Hemoglobin Information Center Policies--IHIC. Variants of the alpha, beta and gamma chains. PMID- 3332002 TI - [Clinical and technical characteristics of alginate hydrocolloid]. PMID- 3332005 TI - Nakahara memorial lecture. Non-receptor type protein-tyrosine kinases closely related to src and yes compose a multigene family. AB - We have determined the total coding sequence of human c-yes, a non-receptor type protein-tyrosine kinase gene, and found that the c-yes gene closely resembles the c-src gene. Recently, two new genes, syn and lyn, were found to encode proteins closely related to the yes product. In addition, we also determined the partial sequence of fgr. These genes together with lck reported by two American groups have very closely related structures and are thought to compose a closely related group of non-receptor type protein-tyrosine kinases. Partial analysis of the structures of these genes indicated that they have identical splicing junctions at all sites so far examined. On the other hand, the erbB-1/EGF (epidermal growth factor) receptor gene and the erbB-2/neu gene have completely different splicing junctions from those of the above gene group even in the kinase domain, although these genes also have protein kinase activity specific for tyrosine residues and the erbB-1 and -2 genes share splicing sites. These results suggest that the genes of the group of six non-receptor type kinases and those of the erbB-1 and erbB-2 gene group are descendants evolved by duplication of two distinct ancestor genes and are members of two distinct multi-gene families. The genes coding for protein kinases may be members of a super-family including multiple distinct gene families. PMID- 3332004 TI - Chromosomal deletion, gene amplification, alternative processing, and autocrine growth factor production in the pathogenesis of human lung cancer. AB - Molecular and cell biologic studies of a large number of lung cancer cell lines of all histologic types have revealed several mechanisms active in the pathogenesis of these cells. Small cell lung cancer (also called "oat cell" lung cancer) has a deletion involving chromosome region 3p(14-23) that is confirmed by DNA restriction fragment length polymorphisms analysis (studies done in collaboration with Dr. Susan Naylor). Several lung cancers of both small cell and non-small cell type (including adeno- and squamous cell lung cancer) express the proto-oncogenes c-, N-, or L-myc, and in some cases more than one of these family members. N-myc appears restricted in its expression to the small cell lung cancer type while c-myc and L-myc can be expressed in both small cell and non-small cell lung cancers. Many lung cancers of all histologic types also express large amounts of p53, which are not correlated with the amount or type of myc gene product expressed. In small cell lung cancer, high levels of myc gene expression are usually associated with gene amplification, and not uncommonly there is rearrangement of some of the amplified copies. In non-small cell lung cancer, expression without amplification or rearrangement of myc genes is seen. In contrast, high level expression of p53 is not associated with gene amplification in any lung cancer type. In addition, to these proto-oncogenes acting at a presumed nuclear locus, there is increased expression of various ras family members and the c-raf-1 proto-oncogene (in collaboration with Dr. Ulf Rapp). Lung cancer cells in tissue culture can grow in medium without serum and few or no other growth factors added. Thus, it appears that lung cancer cells can produce their own growth factors which can act in an "autocrine" fashion. The best characterized example of this is gastrin releasing peptide (GRP, also called bombesin) produced by small cell lung cancer. In at least some small cell lung cancers, interference with GRP action by specific monoclonal antibodies results in inhibition of tumor cell growth in culture and in nude mouse xenografts. Thus, constitutively expressed GRP gene may function as a cellular oncogene under certain circumstances in small cell lung cancer. Based on these observations we are proposing to test monoclonal anti-GRP antibodies in patients. PMID- 3332006 TI - Involvement of the abl oncogene in human chronic myelogenous leukemia. AB - The Philadelphia chromosome found in essentially all patients with chronic myelogenous leukemia is now known to express a chimeric mRNA of 8.5 kb derived from sequences on chromosome 22 and sequences on chromosome 9. The chromosome 9 component of the chimeric RNA is derived from a subset of the exons of the abl oncogene. A portion of the exonic sequences of a gene referred to as bcr on chromosome 22 make up the amino-terminal portion of this chimeric mRNA and gene product. Our laboratory has recently succeeded in obtaining full-length clones of the 8.5 kb mRNA. The sequence analysis of this large mRNA reveals an exceptionally G-C rich 5' untranslated region. A complete open reading frame initiating in sequences of the bcr gene and reading through the abl oncogene segment has been determined. The sequence also reveals an extremely high percentage of serine residues in the bcr segment of the chimeric protein. PMID- 3332007 TI - Molecular genetics of B- and T-cell neoplasia. AB - Specific chromosomal translocations are involved in more than 80% of human B-cell neoplasms. In all these cases the neoplastic phenotype is apparently the consequence of reciprocal chromosomal translocations involving the loci for human immunoglobulin (Ig) chains and either well described cellular proto-oncogenes or putative proto-oncogenes. The juxtaposition of the proto-oncogenes to the Ig loci results in their transcriptional deregulation, because of their proximity to genetic elements within the Ig loci capable of activating gene transcription in cis over considerable chromosomal distances. Sequence analysis of the translocation breakpoints has provided important insights concerning the molecular mechanisms involved in chromosome translocation in B-cells. It appears that the reciprocal translocations contributing to B-cell neoplasia are catalyzed by the same enzymes that are involved in physiological Ig gene rearrangements. The analysis of human B-cell leukemias and lymphomas has also provided considerable information concerning the possible scenarios for B-cell neoplastic transformation. It is clear that the Epstein-Barr virus does not play a direct role in neoplastic transformation, but it may contribute by increasing the number of B-cells at risk of developing chromosome translocations during Ig gene rearrangements. Cytogenetic and molecular genetic analysis of T-cell malignancies is beginning to provide a very similar scenario for neoplastic transformation. The locus for the alpha chain of the T-cell receptor is directly involved, and it apparently juxtaposes to proto-oncogenes or to putative proto-oncogenes leading to their transcriptional deregulation. It seems quite likely that the enzyme system involved in rearrangements of the genes for the T-cell receptor plays a crucial role in the causation of these chromosomal translocations. Thus, the genetic basis of many human B- and T-cell neoplasms may be quite similar. For the future, the challenge resides in trying to characterize specifically the role of both old and new proto-oncogenes in B- and T-cell proliferation, normal and neoplastic. PMID- 3332008 TI - Chromosomal translocations in B-cell derived tumors. AB - The regular activation of the c-myc oncogene by juxtaposition to one of the immunoglobulin loci by chromosomal translocation in Burkitt's lymphoma (BL), mouse plasmacytoma and rat immunocytoma indicates that these translocations represent an essential, i.e. rate limiting step in the development of these tumors. Since the myc-carrying chromosome appears to break at random, but preserves the integrity of the two coding exons, the exclusive involvement of myc (rather than other oncogenes) requires special comment. It must be relatable to the specific functional features of the precursor cells and to the normal role of the myc protein. Recent evidence indicates that the myc gene is regularly turned off before or at the time when the cell enters a pathway that is programmed to lead it towards a resting G0 state. Clonally expanded B-cells are believed to turn into resting memory cells upon waning of the antigenic stimulus. The normal, non-translocated myc-allele is regularly switched off in both BL and murine plasmacytoma (MPC), indicating that the cell has already obeyed a program that involves the down regulation of myc. The Ig-juxtaposed, translocated myc remains highly expressed, however, and may be responsible for keeping the cells in cycle. The possibility that BL and MPC may arise from candidate memory cells, rather than pre-B cells, is also suggested by the fact that all BL-tumors and derived lines make a heavy chain. Since the myc/Ig juxtaposition is a special case of a non-functional rearrangement, this is only expected if the precursor cell would have been preselected for a functional Ig-product. The memory cell hypothesis is further supported by the fact that the majority of BLs make IgM, most MPC make IgA and the rat immunocytomas make IgE. This could correspond to the most frequent type of the memory cell in the anatomical areas and under the physiological or pathophysiological conditions associated with the natural history of each tumor. This brief review is restricted to oncogene activation by chromosomal translocations in B-cell derived tumors. PMID- 3332009 TI - Chromosomal mechanisms in the initiation of human familial mixed cancers. AB - A strong case for a genetic diathesis in human cancer can be made through the analysis of familial aggregations of mixed tumor types. This is particularly true for childhood cancers which have a very low incidence when compared to that of adult cancer and for which common environmental factors appear to play little etiological role. Here are described studies designed to apply molecular genetic analysis toward defining the lesions which predispose to human cancer. We found that the clinically associated tumors retinoblastoma and osteosarcoma share a pathogenetic mechanism entailing aberrant chromosomal segregation events during mitosis which lead to tumor cells homozygous for recessive mutant alleles at the RB1 locus on human chromosome 13 band q14. These results suggest that a rational explanation for the sequential occurrence in these children of two different tumor types is the initial inheritance of a predisposing recessive mutation with broad but specific tissue activity. PMID- 3332010 TI - Altered expression of epidermal growth factor receptors in human bladder and lung tumours. AB - The expression of epidermal growth factor (EGF) receptors on 31 primary bladder and 109 lung tumours was evaluated by immunohistology using two monoclonal antibodies which recognise either the external ligand binding domain or the internal tyrosine kinase domain. At the immunocytochemical level receptor over expression was detected at a higher frequency in squamous lung tumours than in other types of lung tumours. In the bladder tumours those with the highest level of EGF receptor expressions were invasive and poorly differentiated. In all tumours similar receptor expression levels were detected with both antibodies indicating that expression of truncated receptors is not detectable by this method. Analysis of DNA from the bladder and lung tumours failure to show gene re arrangement, except in one unusual case of a carcinosarcoma, thus confirming these histochemical results. Gene amplification accompanied by massive overexpression of receptors was found in 1 of 29 bladder tumours and in 2 of 10 squamous cell carcinomas of the lung. The results suggest that analysis of receptor overexpression could prove useful for diagnosis of certain tumours. PMID- 3332011 TI - The human met oncogene is a member of the tyrosine kinase family. AB - Prolonged exposure of a nontumorigenic human osteogenic sarcoma cell line (HOS) with the direct acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) gave rise to morphologically transformed cells which were tumorigenic in nude mice and termed MNNG-HOS. We have shown that DNA from MNNG-HOS cells will transform NIH/3T3 cells and have isolated greater than 35 kb of human DNA containing an oncogene, termed met. The activated met oncogene expresses a novel 5.0 kb RNA transcript which is a hybrid RNA derived from a DNA rearrangement involving two distinct genetic loci termed met and tpr (translocated promoter region). The met proto-oncogene has been localized to 7q21-q31 by in situ hybridization. This locus expresses a 9.0 kb RNA in fibroblast and epithelial cell lines, but is not commonly expressed in cell lines derived from the hematopoietic cell lineage. In contrast, the tpr locus is on chromosome 1, and expresses a 10.0 kb RNA in all human cell lines tested. The novel 5.0 kb met oncogene RNA is 3' co-terminal with the 9.0 kb met proto-oncogene RNA, while the 5' portion of this RNA uses at least two exons derived from the 10.0 kb tpr RNA. These exons are small and are presumably in the promoter region of both tpr and tpr-met transcripts. Nucleotide sequence analysis of the 3' end of met shows that it is a member of the tyrosine kinase family of genes. Peptide antibody to the C terminal coding region of met immunoprecipitates a 65 kilodalton (kd) polypeptide (p65) in both MNNG-HOS cells and met transformed NIH/3T3 cells. This product also has tyrosine kinase activity in vitro and is presumed to correspond to the tpr met product. The same antibody detects three larger met-related polypeptides of 160, 140, and 110 kd in human fibroblasts and epithelial cells by in vivo labeling with [35S]methionine. However, only one of the three met proto-oncogene polypeptides, p140, appears to be phosphorylated in the in vitro kinase assay. High levels of in vitro 32P incorporation into p140 met are observed in 4 out of 30 human epithelial cancer cell lines tested. Activation of the met oncogene in MNNG-HOS cells results from a DNA rearrangement possibly mediated in vitro by MNNG. The mode of activation of met may therefore be similar to the epidermal growth factor (EGF)R/v-erbB oncogene; or the bcr/c-abl rearrangement present in the Philadelphia chromosome translocation which is found in chronic myelogenous leukemias. PMID- 3332012 TI - Two new retroviral onc genes, sea and jun. AB - Avian leukemia virus S13 induces erythroblastosis, granulocytic leukemia, fibrosarcoma, anemia, and endothelial neoplasia. It transforms chick embryo fibroblasts and primitive erythroid cells in culture and is defective in replication. Its onc gene, sea, is expressed as transformation specific env-sea fusion glycoprotein of 155 kDa. Gp155 is proteolytically processed into gp85env and gp70env-sea. The latter shows tyrosine specific protein kinase activity. Avian sarcoma virus 17 induces fibrosarcoma and transforms chick embryo fibroblasts in culture. Its cell derived onc gene, jun, is not related to known onc genes and appears to be expressed as a gag-jun fusion protein of 55 kDa. The amino acid sequence of jun shows homology in its C-terminal region to the C terminal DNA binding region of the yeast regulatory protein GCN4, suggesting that the jun protein may bind to DNA. PMID- 3332013 TI - Exploring the function of RAS oncogenes by studying the yeast Saccharomyces cerevisiae. AB - The RAS oncogenes comprise a family of genes found to be activated in perhaps 10 20% of human cancers and which have been highly conserved in evolution. Homologs of the mammalian RAS exist in the yeast Saccharomyces cerevisiae (RAS1 and RAS2). We have shown that human ras proteins can complement the loss of RAS1 and RAS2 proteins in yeast, and hence are functionally homologous. Both human and yeast RAS proteins can stimulate the magnesium and guanine nucleotide-dependent adenylate cyclase activity present in yeast membranes. However, RAS proteins do not appear to stimulate adenylate cyclase in vertebrate cells. Our studies indicate that although RAS proteins are essential controlling elements of adenylate cyclase in yeast, they have other essential functions in that organisms. RAS proteins are themselves probably controlled by growth regulatory proteins. PMID- 3332014 TI - Detection of genes with potential of suppressing transforming activity of the v Ki-ras oncogene. AB - We have tried to detect genes which are expressed in normal cells and have the potential of suppressing transforming activity of the Kirsten sarcoma virus oncogene, v-Ki-ras. The experiments involved isolation and characterization of flat revertants from v-Ki-ras-transformed NIH/3T3 cells following either chemical mutagenesis or transfection of a cDNA expression library constructed from total mRNA of normal human fibroblasts. By these procedures multiple genes could be detected which, when transcriptionally activated, suppress different spectra of transformation-associated properties in spite of persistent expression of the v Ki-ras gene product. PMID- 3332016 TI - Proto-oncogene fos: an inducible gene. AB - Proto-oncogene fos is a multifaceted gene, which is expressed during cell growth, cell differentiation, and development. The viral homologue, v-fos, was identified as the resident transforming gene of FBJ-murine osteosarcoma virus which induces bone tumors in mice. Due to an in-fram deletion during the biogenesis of the v fos gene, the products of viral and cellular fos proteins differ at their C termini. Despite different C-termini, both fas proteins are nuclear in their location, and can transform fibroblasts in vitro. However, transformation by c fos gene requires removal of a 67 base pair sequence from the 3' non-coding domain. Proto-oncogene fos is a highly inducible gene in response to a variety of growth factors and differentiation-specific inducers. The transcriptional enhancer and the inducible element of the fos gene have been mapped along with sequences in the 3' non-coding domain which may influence the stability of the c fos transcripts. The c-fos gene transcription is regulated by positively and negatively acting cellular factors. PMID- 3332015 TI - Teratocarcinoma derived from mouse zygotes after the introduction of activated human c-Ha-ras DNA. AB - We attempted to produce transgenic mice harboring the normal or activated human c Ha-ras gene in order to examine the function of activated oncogenes in tumorigenesis. During the process of development, it happened that not only normal looking fetuses were obtained but also malformants, developmentally arrested conceptuses and tumors. Six such abnormally developed embryos were found to have been integrated with the activated human c-Ha-ras gene. One of the two tumors thus obtained was formed after the injection of 6.3 kb DNA fragment containing the gene for p21 with valine at the twelfth position. This tumor was integrated with two copies of the introduced DNA at a particular site in a chromosome and arranged in tandem in a head to tail direction. Histological analysis revealed that this tumor was constructed from at least three types of cells: two originating from different germ layers (one endoderm and the other mesoderm) and the third from an extra-embryonic ectoderm. The other tumor revealed similar features. Thus, it was strongly suggested that these tumors were derived from the very early developmental stage of the embryo, and had features very similar to those of teratocarcinoma. PMID- 3332017 TI - Proteins encoded by the c-myc oncogene: analysis of c-myc protein degradation. AB - We have examined one of the most striking characteristics of the c-myc oncogene protein product: its extremely short half-life relative to all but a few normal cellular proteins. Our studies indicate that the rapid degradation of c-myc proteins is not confined to human and avian cells, where it was first observed, but is found in cells derived from as evolutionarily widely separated species as murine and amphibian as well as in both normal and transformed cells. In addition the rate of degradation appears to be essentially the same throughout the G1, S, and G2 phases of the cell cycle as determined by "pulse-chase" analysis of cell cycle subpopulations separated by centrifugal elutriation. Kinetic analysis of c myc protein turnover utilizing immunoprecipitation from labelled cells or immunoblotting of total nuclei indicate that there is not likely to be a significantly large pool of the protein which is protected from degradation and that no major degradation products can be detected. Evidence that the nucleus plays a role in degradation comes from preliminary experiments which indicate that in enucleated cells the c-myc proteins are stable. We also discuss evidence suggesting that myc proteins are stable in mitotic cells. Finally, using a series of chemical agents we have found conditions which inhibit in vivo degradation. These experiments indicate the involvement of both ATP and metal ions in degradation of c-myc proteins. PMID- 3332018 TI - The pathobiology of proto-oncogenes. AB - The search for genetic damage in neoplastic cells now occupies a central place in cancer research. Diverse examples of such damage are in hand, and they in turn hint at biochemical explanations of why cancer cells go astray. The way may be open to solve the riddles of how normal cells govern their replication and why cancer cells do not. PMID- 3332019 TI - The int-1 proto-oncogene. AB - The int-1 proto-oncogene is the first cellular gene discovered and implicated in tumorigenesis solely on the basis of repeated insertional mutations that activate transcription of the gene. The gene is silent in most tissues but expressed in the embryonic central nervous system, in the late (post-meiotic) stages of spermatogenesis, and in a high proportion of mouse mammary tumor virus-induced carcinomas, when a provirus is inserted upstream or downstream of the coding domain. The functional significance of int-1 in the oncogenic process is supported by the demonstration that murine leukemia virus-based vectors carrying the gene can alter the morphology and growth properties of an established line of mammary epithelial cells. The predicted primary protein product of the int-1 gene is 370 amino acids in length and cysteine-rich; immunoprecipitation with anti peptide antibodies reveals multiple species of int-1 protein, due to asparagine linked glycosylations and probable cleavage of a signal peptide. However, the active product of the gene and its biochemical behavior during normal development and mammary tumorigenesis are not known. PMID- 3332020 TI - Involvement of ras oncogenes in the initiation of carcinogen-induced tumors. AB - More than fifteen different oncogenes have already been identified in human tumors to date. Some of these oncogenes, in particular those of the ras gene family, have been found to be reproducibly activated in a variety of carcinogen induced animal tumor systems. In rats, almost 90% of the mammary carcinomas induced by a single dose of nitroso-methylurea (NMU) possess H-ras-1 oncogenes. We have shown that each of these oncogenes becomes activated by G----A transitions, the type of mutation most frequently induced by NMU. No such mutations have been observed when similar tumors were induced by dimethylbenz(a)anthracene (DMBA), a carcinogen of undefined mutagenic specificity. These results strongly suggest that H-ras-1 oncogenes are activated by NMU during initiation of carcinogenesis. These findings represent the first identification of a cellular locus relevant to neoplasia as a target for the mutagenic properties of a chemical carcinogen. PMID- 3332021 TI - Transformation by raf and myc oncogenes. AB - raf oncogenes were shown to act synergistically with myc in transformation. The contribution of myc was identified as that of a "second messenger" in signal transduction of at least some, competence inducing, growth factors. The role of raf appears to be that of a cytosolic ser/thr specific protein kinase which was placed downstream of ras in the signal transduction of serum growth factors by ras and raf antibody microinjection experiments. Because of the inability of raf to abrogate a cells need for myc inducing competence factors, as well as its synergistic effect with myc, raf was placed downstream of ras in the progression pathway of cellular growth control. We speculate that the basis for synergism with myc might be the ability of raf to activate competence factor induced myc protein or a myc induced protein by phosphorylation. The role of raf in lung tumors was examined by the development of a high incidence mouse model system using ethylnitrosourea as carcinogen and butylated hydroxytoluene as promoter. raf proteins of normal size were expressed at high levels, raf protein vaccination was apparently effective in eliminating the promoted phase of tumor induction. PMID- 3332022 TI - Activation of rat and human c-raf(-1) by rearrangement. AB - Activated c-raf(-1) gene was found in three transformants obtained by transfecting DNAs from rat hepatocellular carcinoma, metastasis of human colon cancer in mesocolon and normal mucosa from a different colon cancer patient. Rat and human activated c-raf(-1) genes were cloned into cosmid vectors; restriction enzyme mapping revealed both activated c-raf(-1) genes to have rearrangement in the center of the normal form of the gene, and the upstream sequences were replaced by unrelated sequences. Using genomic DNA fragments located immediately downstream of the recombination points, the activations of all these c-raf(-1) were shown to have occurred during the transfection process. The recombination points in both the rat and human clones isolated were located in the intron between exons 7 and 8, and nucleotide sequencing around these recombination points showed there to be an inverted repeat which could be involved in inducing in vitro recombination. Nucleotide sequencing of rat and human c-raf(-1) cDNAs revealed the upstream sequences, recombined to the 3' half of c-raf(-1), to be expressed as fusion mRNAs; the production of fused proteins was predicted from a long open reading frame, which is in-frame with the kinase domain encoded from the 3' half of the c-raf(-1) gene. There is a cysteine clustering region in an N terminal region of the c-raf(-1) product deduced from the nucleotide sequence, and this cysteine clustering region was found to be highly homologous to that present in an N-terminal region of protein kinase C, although, in the latter cysteine clusters are present in duplicate. From analogy with the activation mechanism of protein kinase C, the N-terminal region of serine/threonine kinase coded by the c-raf(-1) gene is suggested to be a regulatory part of the enzyme activity, and it proposed that the replacement or truncation of this regulatory part could be the mechanism whereby c-raf(-1) is activated. PMID- 3332023 TI - Role of genes for normal growth factors in human malignancy. AB - The human homologue of the v-sis oncogene encodes one chain of human platelet derived growth factor (PDGF-2). Previous studies have shown that expression of the coding sequence for this growth factor induces malignant transformation of NIH/3T3 cells. We demonstrate the detection of sis/PDGF-2 products indistinguishable from functional PDGF-2 homodimers in human tumor cells. These findings support the concept that expression of the sis/PDGF-2 product in human cells responsive to its proliferative actions can be an important step in the processes leading to malignancy. Unlike sis/PDGF-2, which remains tightly cell associated, another growth factor, termed transforming growth factor alpha (TGF alpha), is actively secreted. Expression vectors for the TGF alpha coding sequence failed to induce primary transformed foci upon transfection of NIH/3T3 cells despite high levels of TGF alpha synthesized by these cells. Moreover, transfectants selected for secretion of high levels of TGF alpha failed to form colonies on contact inhibited NIH/3T3 monolayers or to induce tumors upon inoculation of nude mice. Thus, the ability of a growth factor to induce autonomous in vitro or in vivo growth is dependent upon more than expression of cognate receptors by the cell in which it is synthesized. PMID- 3332024 TI - [Congenital epulis of the newborn. Report of two cases and review of the literature]. PMID- 3332025 TI - [Bilateral cystadenolymphoma of the parotid--Warthin's tumor]. PMID- 3332026 TI - Recurrent habitual abortion, HLA sharing and deliberate immunization with partner's cells: a controversial topic. PMID- 3332027 TI - Can hospital use be a measure of need for health care? PMID- 3332028 TI - Elongation and surface extension of individual cells of Escherichia coli B/r: comparison of theoretical and experimental size distributions. AB - The way individual cells grow and divide uniquely determines the (time-invariant) cell size distribution of populations in steady-state exponential growth. In the preceding article, theoretical distributions were derived for two exponential and six linear models containing a small number of adjustable parameters but no assumptions other than that all cells obey the same growth law. The linear models differ from each other with respect to the timing of the presumptive doubling in their growth rate, the exponential models--according to whether there is or is not a part of the cell that does not contribute to the growth rate. Here we compared the size distributions predicted by each of these models with those of cell length and surface area measured by electron microscopy; the quality of the fit, as determined by the mean-square successive-differences test and the chi 2 goodness-of-fit test, was taken as a measure of the adequacy of the model. The actual data came from two slow-growing E. coli B/r cultures, an A strain (pi = 125 min) and a K strain (pi = 106 min), and a correction was introduced in each to account for the distortion caused by the finite size of the picture frame. The parameter estimates produced by the various models are quite reliable (cv less than 0.1%); we discuss them briefly and compare their values in the two strains. All the length extension models were rejected outright whereas most of the surface growth versions were not. When the same models were tested on A-strain data from a faster growing culture (tau = 21 min), those models that provided an adequate fit to the cell surface area data proved equally satisfactory in the case of cell length. These findings are evaluated and shown to be consistent with cell surface area rather than cell length being the dimension under active control. Three surface area models, all linear, are rejected--those in which doubling of the growth rate occurs with a constant probability from cell birth, at a particular cell age, and precisely at cell division. The evidence in the literature that appears to contradict this last result, rejection of the simple linear surface growth model, is shown to be faulty. The 16 original models are here reduced to five, two involving exponential surface growth and three linear, and possible reasons are presented for our inability to discriminate further at this stage. PMID- 3332029 TI - The Zoom Wigner transform and its application to the analysis of blood velocity waveforms. AB - The analysis of blood velocity using noninvasive Doppler ultrasound is now an important clinical technique. The paper discusses the application of the Wigner transform to the estimation of blood velocity from the Doppler signal. A new type of Wigner transform, the Zoom Wigner Transform or ZWT is developed. The ZWT has certain advantages over the standard Wigner transform, particularly in relation to the frequency resolution of specific components, these are discussed. The final section of the paper considers practical aspects of blood velocity estimation and illustrates the use of the WZT in relation to other methods. PMID- 3332030 TI - The comparative psychology of monogamy. AB - The phenomenon of monogamy is complex both because different characteristics associated with monogamy are displayed by different species and because different authors tend to focus on different characteristics, in part because of the species they study. The essence of monogamy appears to lie in three dimensions- exclusivity of mating, shared parental care, and association. However, many species that can be treated as "monogamous" may fail to show one or more of these characteristics. No one characteristic can be taken as definitive of monogamy. As a rule of thumb, we might consider a system monogamous if two of the three dimensions of monogamy are present. Monogamy, then, is not a unitary construct, but a general term that is useful in delineating a range of phenomena. A fascinating set of questions concerns the determinants of exclusivity of mating, shared parental care, and different kinds of association and when each is and is not shown. This search can be hindered by overreliance on "monogamy" conceived as a unitary characteristic. I find myself following in the footsteps of Frank Beach's Nebraska Symposium paper of 30 years ago in arguing against a unitary concept of monogamy, just as he argued against a unitary concept of "sex drive." Mating systems, such as monogamy, are the product of the behavioral patterns displayed by individual organisms. Our work on voles, like that of Mason and his associates on primates, reveals important differences in the motivational systems of monogamous and nonmonogamous species. Animals show both plasticity within species, as individuals encounter different conditions, and remarkably stable species differences, as laboratory-reared individuals vary reliably. The delineation of these personality profiles of species displaying different proclivities toward mating systems illustrates the utility of the comparative method and can help unravel the underlying causes of a variety of psychological differences, from those affecting mate choice to sex differences in spatial learning. They are thus fundamental to a comprehensive understanding of any species. Although the goal of comparative psychology lies in generating principles of generality concerning behavior rather than in direct extrapolation to humans, results can provide worthwhile hypotheses regarding the evolution of human behavior. Although monogamy and mate choice in humans may be regulated by underlying processes different from those in other species, there are many functional similarities, and both are ultimately the products of natural selection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332031 TI - A comparative approach to vocal communication. PMID- 3332032 TI - A synthetic approach to the study of animal intelligence. PMID- 3332033 TI - Coming to terms with the everyday language of comparative psychology. PMID- 3332034 TI - The Darwinian psychology of discriminative parental solicitude. PMID- 3332037 TI - Transcutaneous electrical nerve stimulation (TNS) and its relationship to placebo therapy: a review. PMID- 3332036 TI - Evaluation of regional cerebral blood flow with 99mTc-d, 1 HM-PAO and SPECT. AB - The imaging of regional cerebral blood flow (rCBF) by 99mTc-d, 1 HM-PAO and SPECT is described. Its relevance to clinical syndromes, such as stroke, transient ischemic attacks, various forms of dementia, epilepsy, and subarachnoid hemorrhage, is reported. PMID- 3332038 TI - 1886 and on: a profession transformed. PMID- 3332035 TI - Perivascular innervation of the cerebral circulation: involvement in the pathophysiology of subarachnoid hemorrhage. AB - The authors describe the perivascular innervation of cerebral circulation. The different nerve fiber systems can be classified as follows: 1. Sympathetic (noradrenaline, neuropeptide Y), 2. Parasympathetic (acetylcholine, vasoactive intestinal peptide/peptide histidine isoleucine (methionine), 3. Sensory (tachykinins, calcitonin gene-related peptide). Each of these systems is outlined by their basic anatomical and physiological facts. Then, the etiology of cerebral vasospasm after subarachnoid hemorrhage is discussed in relation to the cerebrovascular innervation. PMID- 3332039 TI - Routine antenatal ultrasound: a retrospective audit. AB - Of 1021 maternity patients 92.6% had at least one ultrasound scan during pregnancy. Eighty-six point two percent of all patients were scanned before 26 weeks gestation. Ultrasound scanning before 26 weeks gestation resulted in dates being changed by two weeks or more in 14.3%. Ultrasound scanning was an important factor in later pregnancy management in 12% of patients and this figure justifies routine antenatal ultrasound at 16-20 weeks gestation. PMID- 3332040 TI - Bone marrow transplantation. PMID- 3332041 TI - The striking hand of God: leprosy in history. PMID- 3332042 TI - Field observations on the use of anti-sporozoite monoclonal antibodies for determination of infection rates in malaria vectors. AB - Samples of indoor-resting Anopheles gambiae s.1. from Mali and Burkina Faso (West Africa) were processed in order to compare Plasmodium falciparum sporozoite rates obtained by immunoradiometric assay (IRMA) with circumsporozoite (CS) monoclonal antibody and by microscope examination of salivary glands. The immunological method provided sporozoite rates always higher than those obtained by microscope examination. This result does not appear to be related to cross-reactions involving non-sporozoite antigens. A small fraction of IRMA-positive mosquitoes is necessarily negative by microscope, since these mosquitoes actually contain the CS antigen only in the abdomen, presumably in connection with the presence of fully mature oocysts. However, the frequency of these mosquitoes cannot explain in itself an average ratio of 1:2 between microscope and IRMA sporozoite rates. A more important source of difference appears to depend on the detection of positive mosquitoes with low sporozoite numbers which remain more frequently undetected by microscope examination. Failure of salivary gland penetration by sporozoites is also considered as a possible source of discrepancy between the two methods. PMID- 3332043 TI - The influence of multiple risk factors on very low birth weight infants. PMID- 3332045 TI - Idiotypes and antiidiotypic antibodies in health and disease. PMID- 3332044 TI - Scheduling alternatives for administrators. PMID- 3332046 TI - Pseudohypoparathyroidism: clinical expression of PTH resistance. PMID- 3332047 TI - Wilson's disease. PMID- 3332048 TI - Opportunistic parasitic infections associated with the acquired immune deficiency syndrome (AIDS): parasitology, clinical presentation, diagnosis and management. PMID- 3332049 TI - [Hommage to Prof. Michel Jamra]. PMID- 3332050 TI - [Simultaneous demonstration of surface antigens in mononuclear cells in the blood by the immunofluorescence and immunoperoxidase methods: critical study of the methods and preliminary data]. PMID- 3332051 TI - [Thrombotic thrombocytopenic purpura: considerations apropos of a case]. PMID- 3332053 TI - [Decrease in the sensitization index with transfusion of stored blood from a specific donor]. PMID- 3332052 TI - [Usefulness of low doses of antithymocyte globulin prepared in Mexico in the treatment of severe aplastic anemia]. PMID- 3332054 TI - [Development of hematology in Brazil]. PMID- 3332055 TI - Subcellular compartmentalization of calcium-dependent and calcium-independent neutral proteases in brain. AB - In the present experiments, we studied the subcellular distribution of three types of extralysosomal, neutral proteolytic activities in rat telencephalon: (1) nonthiol proteases (NTP), (2) thiol proteases (TP), and (3) calcium-activated thiol proteases (calpains I and II). Subcellular fractionation was performed by using conventional differential and sucrose-gradient centrifugation techniques. The only significant proteolytic activity detected in crude homogenates could be assigned to calpain II, the high-threshold calcium-activated protease. Within the primary fractions prepared from the homogenates, the highest levels of calpain II were found in S3, or the soluble cytoplasmic fraction. Significant activity of the enzyme was also present in P2, the crude mitochondrial/synaptosomal fraction. In contrast, the specific activity of calpain I was greatest in P2 with somewhat lesser enzymatic activity in P1 and S3. Most of the calpain I in P2 was recovered after differential centrifugation through sucrose gradients and lysis of the resultant subfractions. In marked contrast, only a small percentage of the calpain II activity was recovered in the gradient bands. In all, calpain II appears to be predominantly localized in the soluble cytoplasmic compartment while the greatest concentrations of calpain I are found in the soluble components of small glial and neuronal processes (pinched off during homogenization) that constitute the P2 fraction. The highest specific activity of the calcium-independent proteases was obtained in P3, a fraction essentially devoid of calpain, with a secondary peak in P2. Subfractionation of P2 revealed that calcium-independent TP in P2 was associated with mitochondria while the calcium-independent NTP was more uniformly distributed across myelin, synaptosomes, and mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332056 TI - Malaria and urbanization in central Africa: the example of Brazzaville. Part I: Description of the town and review of previous surveys. AB - For a growing number of citizens, the upheavals caused by rapid urban development completely transform malaria epidemiology in tropical Africa. This paper is the first of a series on this phenomenon in Brazzaville, capital of the Congo Republic, where a third of the country's population is already concentrated. After describing the main human and physical geographical aspects of the town, the most significant results of the previous studies of this town and the surrounding rural area are reviewed. They show the existence, until the beginning of the 1950s of a stable, holoendemic situation characterized by a malaria prevalence approaching 90% in children in both urban and rural areas. Since then the intensive development of anti-malaria campaigns in urban areas over about ten years led temporarily to a considerable decrease in the level of endemicity, while in rural areas it remained unchanged. In the 1960s, the vector control and systematic chemoprophylactic measures gradually stopped, permitting the study of a new malaria dynamic related only to the evolving particularities of a changing urban ecosystem. PMID- 3332057 TI - Malaria and urbanization in central Africa: the example of Brazzaville. Part IV. Parasitological and serological surveys in urban and surrounding rural areas. AB - Five schools were chosen in different districts of Brazzaville where the intensity of malaria transmission, determined in a previous study, is representative of the very varied conditions observed in this town in relation to urbanization. The parasitological and serological results found in schoolchildren are analysed according to the level of transmission to which they are exposed, and compared with the results of a longitudinal survey carried out in the rural area of the Brazzaville region. In the urban area malaria prevalences in schoolchildren aged from 5 to 9 years and from 10 to 14 years vary considerably according to the districts. They are, respectively, 78.9% and 84% in Massina, 58.8% and 71.7% in Talangai, 32.3% and 46.9% in Bacongo and 5.6% and 12.6% in Moungali. In Poto-Poto, no positive thick films were found in a representative sample of 62 schoolchildren aged 6 and 7 years who have always lived in this district, and the malaria prevalence is only 6.9% in schoolchildren aged 14 and 15. In the rural area, the malaria prevalence is 76.4% in schoolchildren aged 5 to 9 and 82% in those aged from 10 to 14. According to standard immunofluorescent technique, 63% of children aged 6 and 7 years living since birth in the central part of the Poto-Poto and Moungali districts have no detectable antibodies. In the rural area, all children over 4 years of age are seropositive. These results show that the decrease in vectorial density which accompanies urbanization has considerable parasitological repercussions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332058 TI - The dynamics of infection following BCG and Mycobacterium tuberculosis challenge in T-cell-deficient mice. AB - The purpose of these experiments was to re-evaluate the usefulness of the thymectomized, irradiated, bone marrow reconstituted mouse (TXB mouse) as a model of the effect of immunodeficiency on resistance to mycobacterial infection. It was found that, although TXB mice had no resistance to intravenous infection with Mycobacterium tuberculosis, such mice were able to express moderate resistance to infection with the BCG vaccine, even when given in high doses. It is concluded, therefore, that rather than representing an animal devoid of immunological reactivity, the TXB mouse retains a residual capacity, albeit minimal, to express acquired immunity. PMID- 3332059 TI - A review of blood dyscrasias induced by the antituberculosis drugs. PMID- 3332060 TI - Guinea-pig inoculation for Mycobacterium bovis--is it still necessary? PMID- 3332061 TI - [Use of Silicoater procedure in dentistry]. PMID- 3332062 TI - [Konstantin Neumayer-Zunjevic--stomatologist and public worker]. PMID- 3332063 TI - [In memoriam: Prof. Dr. sci. Zvonimir Kosovel]. PMID- 3332064 TI - Jan Evangelista Purkyne (1787-1869). PMID- 3332065 TI - Idiopathic hypercalciuria. Diagnosis and treatment. PMID- 3332066 TI - Studies on bacteriophage penetration in patients subjected to phage therapy. AB - Two healthy volunteers and 56 patients with suppurative bacterial infections were tested for penetration of oral administered bacteriophage to the blood circulation system and urinary tract. In the blood and urine samples collected from patients before phage therapy application, no presence of "wild phages" was confirmed. Examination performed on the 10th day of phage therapy revealed the presence of bacteriophages in 47 of 56 blood samples tested; positive result of examination was obtained in 9 cases of 26 urine samples. PMID- 3332067 TI - Cancer and thymus extract. AB - Different types of malignant epithelial tumours were found to contain very large amounts of substance immunoreactive with the anti TEX globulin, when studied by direct immunofluorescence method. PMID- 3332068 TI - Glucosteroid (GS)-dependent immunomodulation of immunoglobulin biosynthesis in vitro. I. GS stimulate spontaneous immunoglobulin synthesis. AB - Glucosteroids (GS) enhance spontaneous differentiation of human B lymphocytes to Ig containing plasma cells. The use of the reverse plasque-forming cell (PFC) assay made it possible to subdivide normal donors into GS-responder and non responder inhibitable group. Peripheral blood B cells appear to be especially prone to GS-dependent enhancement of differentiation. While B cells derived from lymphoid organs retain their susceptibility to GS, they are less sensitive inasmuch enhancement of Ig synthesis is concerned. PMID- 3332069 TI - The influence of thymus hormones on the NK cells activity. AB - The influence of thymus hormone preparations on NK cell activity was studied. The following preparations were used: crude extract from calf thymus (TFX), its fraction V (TFX V) and synthetic pentapeptide (TP-5) fragment of native hemopoietin. It was shown that all preparations under study activate NK cells in vitro. The weakest effect was observed in the case of TFX, while both TFX V and TP-5 showed equally good stimulatory properties. The obtained results are discussed. The weak effect of the crude TFX is probably caused by the fact that it contains only 15% of fraction V which is responsible for affinity to the immune system. PMID- 3332070 TI - Studies on the derivatives of aziridine. II. Synthesis and immunopharmacological analysis of substituted amides and anilides of alpha-aziridinyl-beta-/p chlorobenzoyl/-propionic acid. AB - Several new amides and anilides of alpha-aziridinyl-beta-/p-chlorobenzoyl/ propionic acid were synthetized. The beta-/p-chlorobenzoyl/-acrylic acid 2 was used as the substrate. This compound was converted by reaction with appropriate amine into amides and anilides of beta-/p-chlorobenzoyl/-acrylic acid (3-10). These compounds react with ethylenoimine giving appropriate amides and anilides of alpha-aziridinyl-beta-/p-chlorobenzoyl/-propionic acid (11-18). When pharmacologically analyzed, they appeared to possess marked immunotropic activity. The derivatives in question modulated both humoral as well as cellular immune response, the effect being related to the type of substitutent in the amide group. PMID- 3332071 TI - Determination of antibodies to nuclear antigens with special reference to dsDNA using indirect immunoperoxidase. PMID- 3332072 TI - Some hemoglobin modifications in malaria. PMID- 3332073 TI - Burson-Marsteller public information survey. PMID- 3332074 TI - Fractures of the orbit with destruction of the eyeball. 1917. PMID- 3332075 TI - Reconstruction of the anophthalmic socket: state of the art. AB - A successfully rehabilitated anophthalmic socket must hold and support a prosthetic device that mimics the contralateral globe. The goal is symmetry. Static symmetry of the palpebral apertures, canthal angles, and superior sulci are basic objectives. Full versions of the socket implant and prosthesis and full upper lid excursion are definitely desirable but difficult to attain. Adequate lid levels and contours and sufficiently deep conjunctival fornices are necessary to keep the prosthesis in place. Buccal mucous membrane and composite dermis-fat grafts as well as vascular pedical flaps can be used to expand contracted sockets. Canthal tendon shortening and fixation can be effectively used to reestablish lid and canthal contours and to support the prosthesis. PMID- 3332076 TI - Complex orbital trauma: the role of rigid fixation and primary bone grafting. AB - High-velocity trauma to the orbit is characterized by complete disruption of the orbital rim and comminution of the walls of the orbital cavity. The incidence of associated injury to the intraorbital contents, and to contiguous facial skeletal structures, is significant. Failure to recognize and repair the skeletal injuries results in progressive contracture of the overlying soft tissues, collapse of the bony framework of the orbit, and atrophy of incarcerated intraorbital contents. Immediate orbital reconstruction aims to restore and maintain the normal anatomy of the craniofacial skeleton. The introduction of computed tomography (CT) and craniofacial surgical techniques facilitates comprehensive evaluation of orbital fractures. Further adaptation of the principles and techniques of rigid internal skeletal fixation and primary bone grafting permits a stable, three-dimensional, anatomic reconstruction of virtually any traumatic orbital deformity. PMID- 3332077 TI - Autogenous bone in orbital reconstruction. AB - Autogenous bone grafts play a major role in facial and orbital reconstruction following trauma. We discuss harvesting rib, iliac, and calvarial bone grafts for such cases, and point out the controversies in the use of alloplastic versus autogenous grafting materials. PMID- 3332078 TI - Secretion and ion transport in airways during inflammation. AB - Water and secretions interact in airways to produce the sol and gel layers that allow for entrapment of foreign materials and subsequent clearance by ciliary movement and by cough. Active Cl ion transport produces fluid, and this process is activated by products of mast cells (leukotrienes), eosinophils (major basic protein), and by other inflammatory mediators (prostaglandins, bradykinin). Gland secretions produce the bulk of the volume of secretions. Airway irritation stimulates gland secretion reflexly via vagal muscarinic pathways. Recently, the sensory nerves have been discovered to release substance P and other neuropeptides when the airways are irritated. The stimulatory effects of neuropeptides on gland secretion (and on other inflammatory sites) are modulated by enkephalinase a membrane-bound enzyme that cleaves neuropeptides and thereby inactivates them. Up- or down-regulation of enkephalinase is predicted to change the degree of inflammatory response to neuropeptides. Finally, the cell surface of airway epithelial cells have been discovered to secrete large molecular weight glycoconjugates; these secreted products are increased markedly by a series of proteinases produced by inflammatory cells (neutrophils, mast cells) and by bacteria. Their exact physiologic roles are still unknown but they may contribute to the bulk and viscoelastic properties of airway secretions, and they may serve an important role in bacterial, viral and inflammatory cell adhesion. PMID- 3332079 TI - Fluid transport by airway epithelia. AB - Airway epithelia possess transepithelial ion transport processes which may help to regulate the fluid content of airway secretions. Chloride secretion promotes fluid movement from blood to airway lumen. Active absorption of Na favours fluid movement in the opposite direction. The balance between these two processes can be altered by a number of agents which stimulate Cl secretion. The importance of ion transport for normal mucociliary clearance is suggested by the finding that airway epithelia in patients with cystic fibrosis are unable to secrete chloride. This defect may cause the characteristically sticky and tenacious mucous secretions which are the major cause of death in this disease. PMID- 3332080 TI - Dynamic light scattering methods for biorhelogy. AB - Several noninvasive light scattering techniques are reviewed that can be utilized in rheological studies of mucus and other soft biological matrices. Included are quasielastic light scattering techniques to determine the compressibility moduli of polymer lattices, resonance methods that can be used to measure the shear modulus of weak gels, assays that probe the swelling and contraction of mucin aggregates, and microscope based light scattering techniques to probe gelation within single cells. PMID- 3332081 TI - Diagnostic and therapeutic applications of antiplatelet monoclonal antibodies. AB - The interaction of platelets with natural and artificial surfaces is briefly reviewed, emphasizing the role of the platelet glycoprotein Ib and IIb/IIIa receptors. Studies utilizing monoclonal antibodies to these receptors for the diagnosis and therapy of hemorrhagic and thrombotic disorders are described, indicating the potential of such agents as platelet inhibitors. PMID- 3332082 TI - Molecular cloning and characterization of the gene coding for red cell membrane skeletal protein 4.1. AB - The application of molecular biology to the study of the human erythrocyte membrane is presented in this report. We describe the strategy employed to clone DNA sequences encoding the membrane skeletal protein, protein 4.1. We demonstrate how these sequences may be utilized to deduce detailed structural and functional information about the 4.1 polypeptide. We also illustrate the use of cloned 4.1 DNA sequences as probes to explore the structural organization of the protein 4.1 gene in normal individuals and in patients with dysfunctional erythrocyte membranes. Ultimately it will be possible to generate a molecular description both of the structural proteins which constitute the membrane skeleton, and of the genetic mechanisms regulating their expression in erythroid and nonerythroid cells. PMID- 3332083 TI - Hypercoagulability and ischaemic heart disease. AB - Thrombogenesis is increasingly recognised as an immediate cause of most major clinical episodes of ischaemic heart disease (IHD) and the haemostatic system makes a significant contribution to the development of atheroma. It is therefore important to consider how far concepts of increased thrombotic tendency and hypercoagulability can be demonstrated in reality. A number of general observations do suggest that characteristics of the circulating blood influence the course of events in IHD--for example, the occurrence of IHD or stroke in young women using oral contraceptives in whom advanced arterial wall changes are not a feature. Epidemiologically, the coagulation system has been more rewarding than the study of platelets. The Northwick Park Heart Study (NPHS) has demonstrated a strong relationship between the level of factor VII activity and the later incidence of IHD. Several biochemical characteristics of factor VII suggest that this relationship may well be one of cause and effect. There is growing evidence that high levels of factor VII activity lead to high levels of thrombin production. In addition to NPHS, three other prospective studies have shown an association between high levels of plasma fibrinogen and IHD incidence. Again, there are several reasons for believing that this association, too, is of pathogenetic significance. Dietary fat intake is a major determinant of the factor VII activity level, and smoking of the fibrinogen level. Hypercoagulability determining IHD is best defined, on present evidence, as over activity of procoagulatory influences (whereas hypercoagulability leading to venous thrombosis is predominantly manifested as underactivity of natural defence mechanisms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332084 TI - High risk lymphoblastic leukemia in children: prognostic factors and management. AB - Most of the presenting clinical and biological features that have prognostic significance in childhood acute lymphoblastic leukemia are closely related, although they are not equally important. The predictive value of these factors can vary with the efficacy of the therapy delivered. Although there are no uniform criteria to define a high-risk group, an initially high leukocyte count and an age less than 1 or greater than 10 years at diagnosis are universally accepted as the most powerful indicators of a poor outcome. With advances in immunology and genetics, blast cell immunophenotypes and karyotypic abnormalities have emerged as independently significant prognostic factors. With this information, therapy can be tailored for patients at various risks of treatment failure. Using early aggressive therapy, more than 60% of patients are expected to be long-term survivors, but better therapy is still needed for those at high risk of relapse. Innovative approaches, such as bone marrow transplantation, phenotype-specific treatment, or pharmacokinetic-directed therapy, are being tested. PMID- 3332085 TI - The myelodysplastic syndromes. AB - The myelodysplastic syndromes constitute a fascinating model for monoclonal premalignant disorders. Haemopoiesis is 'dysplastic' with inefficient maturation of a slowly expanding or sometimes of a stable population, of blood cell precursors. About one third of the patients evolve into acute leukaemia, the result of either a progressive expansion of the original clone or a new mutation producing a more malignant subclone. The majority of patients suffer from the results of bone-marrow insufficiency, with pancytopenia and possibly immune deficiency. Characteristic karyotype anomalies involving mainly chromosomes 5, 7 and 8 are seen in half the patients. These same chromosomes are known to carry different oncogenes. The myelodysplastic syndrome occurs mainly in the aged and there is a moderate male preponderance. The incidence is still unknown but is probably similar to that of acute leukaemia. The etiology is also unknown; however, a secondary myelodysplastic syndrome precedes acute myeloid leukaemia, as a late consequence of chemo- and radio-therapy in treated Hodgkin's disease. This suggests that environmental mutagens might also be involved in primary myelodysplastic syndromes. Treatment remains highly unsatisfactory but a few recent developments improve prognosis, at least in the younger patient. PMID- 3332086 TI - The prophylaxis and treatment of malaria. AB - Because malaria remains a major worldwide public health problem, and resistance to currently available drugs is becoming more prevalent, interest has focused on the clinical pharmacology of antimalarials. Previously many of these drugs had been little studied, and it is now hoped that increasing information on the disposition of current drugs, and those under development may improve their rational use. This article therefore reviews the current information on the pharmacology of the commoner drugs, and describes possible future tools to combat malaria. PMID- 3332087 TI - Mechanisms and management of chemotherapy-induced nausea and vomiting. AB - Only in recent years has serious attention been given to the control of chemotherapy-induced emesis (CIE) which is to the patient a most obnoxious side effect. Important advances in the understanding of the mechanisms of CIE have led to the scientific appraisal of potential anti-emetics whilst additional, useful anti-emetics have appeared by serendipity. CIE has largely been studied in trials separating either cis-platinum (severely emetic) or non-cis-platinum(moderately emetic)-induced emesis. In the evolution of these trials the difficulty and importance of accurate evaluation of emesis has been revealed and the whole area of psychogenic emesis opened to investigation and treatment. Phenothiazines and butyrophenones have a definite modest anti-emetic role against moderately emetogenic chemotherapy but increasingly corticosteroids, benzodiazepines, high dose metoclopramide and cannabinoids are being used with great effect even with severely emetic drugs. Combination anti-emesis has further improved control rates and new schedules of currently available anti-emetics are now proving their worth. Major advances in anti-emetic control have been achieved recently and every patient at risk of CIE should have good control, if not total abolition, of emesis with appropriate use of anti-emetics. PMID- 3332088 TI - The value of indium-labelled leucocytes in clinical practice. AB - Following intravenous injection, autologous 111In labelled-leucocytes migrate to sites of inflammation, where they can be imaged with the gamma camera. The principle underlining the labelling technique is exposure of a population of leucocytes or purified granulocytes to a lipophilic 111In complex, such as 111In oxine or 111In tropolonate. As a result of cell activation, the in vitro manipulation to which the leucocytes are subjected modifies their biodistribution early after re-injection. Separation and labelling in plasma-enriched media, however, limits this activation and promotes early migration into inflammatory foci. PMID- 3332089 TI - Aspirin and other antiplatelet drugs in the prophylaxis of thrombosis. AB - Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. After a myocardial infarction it reduces the risk of death by about 10% and of coronary incidence (coronary death or definite myocardial infarction) by about 25%. These effects appear to be additive with those of beta-blocking drugs. Aspirin also reduces the risk of occlusion of aortocoronary saphenous vein grafts by about half. In transient cerebral ischaemia, aspirin may reduce the risk of stroke and death by 50%. In most clinical trials to date the daily dose of aspirin ranges from 325 mg to 1400 mg. Interest in very low doses of aspirin (less than 60 mg daily) is considerable but has yet to be translated into proven clinical benefit. Dipyridamole has not been shown to be effective as an antithrombotic when used alone. Its antiplatelet action ex vivo may be enhanced by combination with aspirin but clinical trials have shown relatively little advantage of the combination over aspirin alone. Sulphinpyrazone has not become established as a first line antithrombotic drug. Epoprostenol is useful in extracorporeal circulations to prevent platelet consumption and possibly in severe inoperable peripheral vascular disease. PMID- 3332090 TI - The role of pentostatin (2'-deoxycoformycin, dCF) in the management of lymphoproliferative malignancies. AB - Laboratory and clinical data relating to the use of 2'-deoxycoformycin in human disease are reviewed. Pentostatin is an inhibitor of adenosine deaminase, an enzyme that is important for purine metabolism, but more than one mechanism may be involved in its cytotoxic action. Early studies with dCF employed large doses and for the most part were conducted in patients with acute lymphocytic leukaemia: responses were brief and relatively few, and severe renal, hepatic, and central nervous system toxicity were encountered, leading to temporary abandonment of clinical trials. More recently, it has been shown that dCF is effective in much smaller doses, with considerably less toxicity. It has proved to be more effective in low-grade lymphoid malignancies (chronic leukaemias, indolent lymphomas) than in more undifferentiated neoplasms (acute leukaemias, lymphoblastic and immunoblastic lymphomas), and is outstandingly effective in hairy cell leukaemia, both as initial therapy and after failure of splenectomy and interferon. Pentostatin is profoundly immunosuppressive: generally this is considered a disadvantage but its potential therapeutic exploitation merits investigation. Despite extensive knowledge of its biochemical effects, the optimal dose regimen of dCF and the value of combining it with purine antagonists remain to be defined. PMID- 3332091 TI - Drug-mediated thrombocytopenia. AB - Thrombocytopenia due to drug-dependent antibodies most frequently occurs with quinine/quinidine and with heparin. Considerable evidence has accumulated about the mechanism of action of quinine/quinidine-induced antibodies but less is known about the effect of heparin. Although there is controversy, it is likely that the action of quinine/quinidine-induced antibodies follows a loose association between drug and platelet with antibodies acting independently of the Fc receptor. There is strong evidence that the complex of glycoprotein Ib and glycoprotein IX, absent in the Bernard-Soulier syndrome, provides the binding site for quinine/quinidine-dependent antibodies. It also appears that the two glycoproteins must be present in complex form for antibody binding to occur. There is some heterogeneity of quinine/quinidine-dependent antibodies since there are reports of a proportion of patient antibodies reacting with other membrane determinants or acting independently of the drug. Heparin-induced thrombocytopenia may be the consequence of a direct effect, or a more serious condition associated with thrombosis may occur when heparin-dependent antibodies are formed. The mode of action of these antibodies and the nature of their antigenic determinants remain unclear. Recognition of heparin-associated thrombocytopenia is important so that serious bleeding or thrombotic sequelae can be forestalled. PMID- 3332092 TI - Immunologic thrombocytopenic purpura in patients at risk for AIDS. AB - HIV-seropositive homosexuals, narcotic addicts and hemophiliacs develop a new syndrome of immunologic thrombocytopenic purpura (ITP) which is clinically indistinguishable from classic autoimmune thrombocytopenic purpura (ATP) with respect to increased megakaryocytes in the bone marrow, peripheral destruction of antibody-coated platelets, negative serology for SLE, response to treatment with prednisone and/or splenectomy. Eleven of 79 homosexual patients have developed AIDS 2 to 43 months after the diagnosis of ITP (mean, 22 months). The mechanism of the ITP appears to be different in homosexuals and narcotic addicts when compared to classic ATP. Homosexuals and narcotic addicts have markedly elevated platelet-bound IgG and C3C4 (2.5-4-fold ATP levels), PEG-precipitable circulating immune complexes and anti-F(ab')2 antibodies (absent in ATP). There is no inverse relationship between platelet-bound IgG and platelet count and platelet antibody is usually not elutable from washed platelets as is the case with classic ATP. Homosexual patients do not have 7S platelet antibody in their sera as do classic ATP patients, but appear to have immune complex deposition on their platelets, possibly due to the presence of anti-F(ab')2 antibodies. Narcotic addict patients do have detectable 7S platelet antibody but also appear to have immune complex deposition on their platelets, possibly due to anti-F(ab')2 antibodies. The anti F(ab')2 antibodies are of the IgG class. They react with autologous, homologous patient and healthy control F(ab')2 fragments. Some anti-F(ab')2 antibodies have broad reactivity, others are more limited. It is postulated that some of the anti F(ab')2 antibodies may be responsible for the thrombocytopenia. PMID- 3332093 TI - Value and application of automation in laboratory diagnosis of haemostatic disorders. AB - There is a bewildering variety of instrumentation available for automation of coagulation procedures. The advantages and draw-backs of the most widely-used types are discussed to help the prospective purchaser to decide the most suitable instrument for his needs. Operator satisfaction is of considerable importance. Anticoagulated plasmas give shorter clotting times on many instruments as compared with the manual method which may necessitate an extrapolation curve or change of therapeutic range. An instrument, carefully selected, can increase the throughput of samples and improve the overall accuracy and precision of results. PMID- 3332094 TI - The significance of endogenous erythroid colonies (EEC) in haematological disorders. AB - The myeloproliferative disorders are the result of an underlying abnormality of the pluripotential stem cell. One feature of this abnormality is a greatly increased sensitivity of the committed erythroid progenitors (BFU-E and CFU-E) to the hormone erythropoietin. Culture in vitro of these bone marrow or peripheral blood cells results in the growth of a proportion of colonies in the absence of added erythropoietin. These endogenous erythroid colonies (EEC) are seen in the great majority of cases of polycythaemia vera, as well as in some cases of thrombocythaemia, chronic myeloid leukaemia and idiopathic myelofibrosis. The presence of EEC appears to be a marker for the stem cell mutation and may serve to distinguish the neoplastic disorders from reactive increases of red cell mass or platelet numbers. Their absence in idiopathic erythrocytosis may also distinguish this condition from early polycythaemia vera and be useful in deciding on appropriate treatment. In patients with even a modest increase in the platelet count endogenous colonies provide firm evidence for a myeloproliferative disorder. Provision of myelosuppressive treatment can avert or improve vaso occlusive or haemorrhagic complications. The mechanism of erythropoietin hypersensitivity is unknown but it has been shown to be a feature acquired rather late in maturation and by only a proportion of the progeny of the mutated clone. Normal erythroid progenitors co-exist with these abnormal cells in polycythaemia vera and the way in which their growth in vivo is inhibited has yet to be determined. PMID- 3332095 TI - Prostaglandins in the pathogenesis and prevention of vascular disease. AB - Metabolism of arachidonic acid gives rise to a number of products with potent, and sometimes opposing, biological actions. Prostacyclin, the main product of arachidonic acid in vascular tissue, is a vasodilator and inhibitor of platelet aggregation whereas thromboxane A2, produced by the platelet, is a vasoconstrictor and inducer of platelet aggregation. Generation of these products may be modified in certain diseases, such as atherosclerosis and diabetes, so that prostacyclin production is reduced and thromboxane A2 production increased, resulting in a pro-thrombotic condition. Synthesis of arachidonic acid metabolites may be manipulated using drugs such as aspirin or imidazole analogues which selectively inhibit different enzymes in the metabolic pathway. Such drugs have proved beneficial in the treatment of some vascular disorders. Clinical use of prostacyclin has shown it to be effective in the treatment of peripheral vascular disease, Raynaud's Syndrome and pulmonary hypertension. Stable analogues of prostacyclin are being developed which may lead to a separation of the vasodilator and anti-platelet actions of prostacyclin. PMID- 3332096 TI - Immunologic classification of lymphoma and lymphoid leukemia. AB - Important insights into lymphocyte differentiation and the cellular origins of lymphoma and lymphoid leukemia have been gained through the use of monoclonal antibodies that define cell surface antigens and molecular probes that identify immunoglobulin and T cell receptor genes. Results of these studies have been combined with markers such as surface membrane and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte receptors on T lymphocytes, and cytochemical stains. Utilising all of the above markers, it is now clear that acute lymphoblastic leukemia (ALL) is heterogeneous. Furthermore, monoclonal antibodies that identify B cells such as the anti-B1 and anti-B4 antibodies in combination with studies of immunoglobulin gene rearrangement have demonstrated that virtually all cases of non-T-ALL involve B lymphocytes. At least six distinct subgroups of non-T-ALL can now be identified. T-ALL is subdivided by the anti-Leu 9, anti-Leu-1, and additional antibodies that separate T lymphocyte subsets into three primary subgroups. Monoclonal antibodies are also useful in the subclassification of non-Hodgkin's lymphoma, and certain distinct markers can be correlated with morphologic classification. PMID- 3332097 TI - Monoclonality in human T-cell disorders. AB - The genes coding for the T-cell antigen receptor have recently been cloned. They have proven to be invaluable tools for the study of the molecular mechanisms governing T-cell recognition of foreign antigens associated with histocompatibility antigens. In addition, they have also provided sensitive means of detecting clonal cell populations and determining cell lineage. In this review we describe the general organisation of these genes, the results of their utilization in the analysis of hematological pathologies, and discuss the possible implications of the involvement of these genes in translocations observed in certain T-cell malignancies. PMID- 3332098 TI - The treatment of acute non-lymphocytic leukemia. AB - The treatment of acute nonlymphocytic leukemia involves a two stage approach. During the first stage, remission induction, cytotoxic drugs are administered to return hematopoiesis to normal. During the second stage, therapy is administered in an attempt to prolong the duration of remission. The clinical approaches and the problems incurred during these stages are not identical. At the time of diagnosis a decision must be made regarding whether or not the patient is likely to benefit from chemotherapy. If the answer is in the affirmative, then a decision must be made regarding the appropriate chemotherapeutic regimen. The optimal approach for the treatment of patients appears to vary depending on the age of the patient and whether or not there is a history of toxic exposure in the past. Overall remission rates vary from 40% to 85% depending upon the age of the patient and the patient's past history. Patients whose leukemia is induced into complete remission benefit from therapy administered after complete remission is attained. The optimal therapy, however, has not as yet been clearly defined. Conventional maintenance therapy appears to provide little benefit. On the other hand, the more intensive therapies are associated with substantial risk to the patient. The role of these modalities in the treatment of older patients is currently under investigation. PMID- 3332099 TI - Hereditary elliptocytosis, spherocytosis and related disorders: consequences of a deficiency or a mutation of membrane skeletal proteins. AB - The membrane skeleton, a protein lattice that laminates the internal side of the red cell membrane, contains four major proteins: spectrin, actin, protein 4.1 and ankyrin. By mass, the most abundant of these proteins is spectrin, a fibre-like protein composed of two chains, alpha and beta, which are twisted along each other into a heterodimer. At their head region, spectrin heterodimers are assembled into tetramers. At their distal end, these tetramers are interconnected into a two dimensional network by their linkage to oligomers of actin. This interaction is greatly strengthened by protein 4.1. The skeleton is attached to the membrane by ankyrin, a protein that connects the spectrin beta chain to the major transmembrane protein band 3, the anion channel protein. Additional attachment sites are those of protein 4.1 with several glycoproteins, namely glycophorin A and C, as well as direct interactions between spectrin, protein 4.1 and the negatively charged lipids of the inner membrane lipid bilayer. Hereditary spherocytosis, elliptocytosis and pyropoikilocytosis represent a group of disorders that are due to deficiency or dysfunction of one of the membrane skeletal proteins (Fig. 1). Known deficiency states include that of spectrin, ankyrin and protein 4.1. Severe spectrin and ankyrin deficiencies (with decrease in spectrin and ankyrin contents to about 50% of the normal amount) are both rare disorders associated with severe autosomal recessive hereditary spherocytosis. On the other hand, mild spectrin deficiency is found in the majority of patients with autosomal dominant spherocytosis in which the degree of spectrin deficiency correlates with the clinical severity of the disease. Protein 4.1 deficiency, in contrast, is associated with hereditary elliptocytosis, which in certain populations constitutes about 20% of all such patients. Known skeletal protein dysfunctions include mutants of both alpha and beta spectrin that involve the spectrin heterodimer self-association site. These are clinically expressed as hereditary elliptocytosis (HE) and a closely related disorder, hereditary pyropoikilocytosis (HPP). At the level of protein function, this defect can be detected by analysis of the content of spectrin dimers and tetramers in 0 degrees C low ionic strength extracts of red cell membranes. Their structural identification is accomplished by limited proteolytic digestion of spectrin followed by two-dimensional tryptic peptide mapping.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332100 TI - Results of programmes for antenatal detection of thalassemia in reducing the incidence of the disorder. AB - The characteristics and the effectiveness of programmes designed to prevent beta thalassemia major present in high frequency in several areas of the world such as Cyprus, Greece and Sardinia are reviewed. All these programmes are based on heterozygote detection, counselling and foetal diagnosis. The target population for screening have been couples at marriage, conception or early pregnancy. Awareness of the problem and involvement of the population was achieved via mass media or personal approaches through lectures or discussions. Parent's Association were consulted and have been actively involved. Information leaflets have been made available to prospective couples at several critical areas. Education on thalassemias was introduced into the school curriculum. Counselling was based on a private interview at which the several options available were discussed with the individual carrier or the couple. Prenatal diagnosis was chosen by the large majority of couples counselled. All these programmes resulted in a decline of thalassemia major births by 50-97%. The reasons for residual cases were mostly lack of information and, less frequently, misdiagnoses or refusal of fetal diagnoses. PMID- 3332101 TI - Inherited disorders of vitamin B12 metabolism. AB - Inherited disorders of vitamin B12 include those which involve the inability of the vitamin to be absorbed from the gut and transported to the appropriate tissues, and those in which the vitamin is not utilised by target cells. The former include intrinsic factor abnormalities, selective malabsorption of vitamin B12 with proteinuria, and deficiencies of transcobalamin I and transcobalamin II. The latter include a defect in the release of free vitamin B12 from lysosomes (cblF), and defects in the formation of both vitamin B12 cofactors (cblC, cblD) or of adenosyl-B12 (cblA, cblB) or methyl-B12 alone (cblE, CblE variant). This article reviews the major clinical manifestations of these diseases, and provides an approach to the diagnosis of transcobalamin II deficiency and the cbl mutations using cultured cells. PMID- 3332102 TI - Role of chromosomal abnormalities in chronic lymphocytic leukemia. AB - Chromosomal aberrations occur in both B-CLL and T-CLL. The polyclonal B-cell mitogens, in particular Epstein-Barr virus and lipopolysaccharide from E. coli, have been used successfully to reveal chromosomal abnormalities in 40-60% of patients with B-CLL, while T-cell mitogens have shown chromosomal aberrations in T-CLL. The most common clonal chromosomal aberration in B-CLL is an extra chromosome 12, alone or together with other abnormalities. Other common aberrations are 14q+, structural aberrations on 6, 11, 12 and 13. Proto-oncogenes are frequently located close to breakpoints. The proto-oncogene c-K-ras is located on chromosome 12 and an abnormal transcript has recently been implicated in a subset of B-CLL-patients. An extra chromosome 12 as well as multiple chromosomal abnormalities in B-CLL appear to predict a less favourable prognosis. T-CLL is in most patients characterized by an inv(14), an extra 8q and structural abnormalities in chromosome 7. The genes for the specific T-cell receptor as well as the immunoglobulin heavy chain are located on these chromosomes. Chromosomal aberrations appear to have pathogenetic importance in both B-CLL and T-CLL. PMID- 3332103 TI - The role of autologous bone marrow transplantation in the treatment of malignant disease. AB - This short review of autologous bone marrow transplantation (ABMT) has a distinct clinical emphasis and concentrates particularly on adult acute leukaemia and lymphoma in which the greatest amount of current clinical experience lies. In the early part of the review we discuss how escalations of dose of chemoradiotherapy might allow ablation of both marrow-derived (leukaemia) and non-marrow-derived disease (lymphoma and solid tumour) provided that haemopoiesis is reintroduced into the host in the form of autologous marrow stem cells, and how cryopreservation techniques have allowed this to proceed. Whilst discussing ABMT in acute leukaemia we describe initial results possibly suggestive of an improvement on current consolidation/maintenance chemotherapy regimens but emphasis that we are dealing only with heterogeneous registry data and not randomised controlled trials. We also suggest that there is no useful data as yet as to the value of purging autologous acute leukaemia marrow. The lymphoma data is described which may suggest a useful role of high dose therapy with ABMT in relapsed disease-timing of ABMT may need to differ profoundly in HD from NHL. Current ABMT data in lymphoma suggests that local relapse at sites of previous disease remain the major problem and emphasises the difficulties of finding satisfactory ablative regimens and timing the selection of patients at particular points in the natural history of their disease. Finally, we emphasise that although solid tumours may numerically represent the largest group of potential candidates for ABMT, the picture in this area remains essentially one of failure to be able to ablate the underlying disease despite increments in chemoradiotherapy and ABMT. PMID- 3332104 TI - Chromogenic substrates in haemostasis. AB - Advances in knowledge of the structure-function relationships of the proteins involved in haemostatic pathways, have made it possible to synthesize small peptides which mimic the active site of many of the serine proteases concerned. Attachment to the cleavage site of such synthetic peptides, of a detector molecule such as para-nitroaniline which, when released, produces a coloured compound has enabled many of the enzyme reactions of haemostasis, and most of the co-factors and naturally-occurring inhibitors, to be individually and sensitively quantitated. Chromogenic substrate assays are very specific and overcome the criticism levelled at many conventional assays that, being based on the speed of formation or the rate of destruction of a fibrin clot, they frequently involve enzymatic reactions in addition to that being examined. Moreover, chromogenic substrate assays are generally simple and quick to perform and are readily automated. They are thus economical of manpower and, more importantly from the point of view of patient care, they permit the rapidly-changing status of those with acute derangements of haemostasis to be monitored more frequently and comprehensively than is possible using some conventional assays. Chromogenic substrate assays have some limitations, however. Since they mimic only a small portion of the natural substrate, they may not be sensitive to structural defects elsewhere in the molecule, and may thus not totally reflect biological activity. Though technically simple to perform, the defined incubation times and temperatures must be rigidly adhered to if reliable results are to be obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332106 TI - Perioperative blood transfusion and solid tumour recurrence. AB - Evidence regarding the association of blood transfusions with recurrence of solid tumours is largely conflicting. This is perhaps unsurprising given the retrospective nature of the studies performed to date, the complexity of the disease and its treatment, and variations in local transfusion practices. Nonetheless, new data demonstrating that transfusions of whole blood, as opposed to red cell concentrates, are associated with earlier cancer recurrence are most readily explained by a cause and effect relationship. There is a growing literature documenting previously unforeseen immunologic consequences of homologous blood transfusion. These possible clinical consequences include earlier cancer recurrence and increased susceptibility to infection with bacteria and viruses. The questions raised in this review can be answered conclusively only by controlled prospective studies. For the present the prudent clinician will select red blood cells rather than whole blood for transfusion, employ autologous transfusions whenever feasible, and recognize that blood transfusion is a therapy with considerable benefits, but also considerable risks. PMID- 3332105 TI - Chronic granulomatous disease--pieces of a cellular and molecular puzzle. AB - Chronic granulomatous disease (CGD) is an inherited disorder in which phagocytes are unable to manufacture microbicidal oxidants. The disorder may be classified into subtypes depending upon the mode of transmission (X-linked or autosomal recessive) and the presence or absence of a heme protein designated 'cytochrome b558' (see below). Patients with CGD suffer recurrent deep-seated bacterial infections that respond poorly to therapy, slowly destroy affected tissues and eventually claim the patients' lives. Clinical deterioration is slowed, though not stopped, by the current practice of placing CGD patients on prophylactic antibiotics. Microbicidal oxidant production fails in CGD because of a defect in the enzyme responsible for the production of superoxide (O2-), the single precursor from which all the microbicidal oxidants ultimately arise. This enzyme, the respiratory burst oxidase, is a membrane-bound oxidase that catalyses the one electron reduction of oxygen to O2- at the expense of NADPH. The oxidase is dormant in resting phagocytes, but comes to life when the phagocytes are exposed to bacteria or other appropriate stimuli. Components related to the respiratory burst oxidase include cytochrome b558 (one of those subunits has recently been shown to be encoded by a gene that is defective in the most common form of CGD), a flavoprotein that participates directly in O2- production, a cytosolic factor needed for the activation of the oxidase, and a group of 48K phosphoproteins. How these components relate to each other and to the O2- -forming activity of the oxidase is currently under active investigation. PMID- 3332107 TI - The management of the limb in acute venous thrombosis. AB - This review addresses the management of the limb in patients with deep vein thrombosis. The concepts that underline such treatment are reviewed and the importance of objective diagnosis before the institution of long term therapy is stressed. Management is considered in relation to the extent of segmental venous involvement and to the use of Heparin, Streptokinase, Warfarin and surgical therapy. There is a lack of adequate and comprehensive follow up data on the limb in patients with deep vein thrombosis and in particular there are few objective studies relating to the short and long term sequelae as far as valvular function is concerned. There is uncertainty concerning the appropriateness of continuing compression therapy and the value of such therapy in reducing long term morbidity. The importance of recognising the potentially severe ischaemic consequences of massive venous thrombosis are described, together with an outline management plan. The importance of short and long term follow up studies of the limb is stressed particularly in relation to potential changes in methods of treatment. PMID- 3332108 TI - Current recommendations in prevention of thrombosis in surgery. AB - Fatal pulmonary embolism is a major cause of postoperative death. When no prophylaxis is given in general surgery, it has a frequency of about 1%. Apart from the immediate risk to life, one must also consider the late sequelae of extensive deep vein thrombosis--swelling of the legs, varicose veins, ulceration and other trophic changes which represent an equally distressing situation. Recently, three large-scale surveys have been published, where the data of over 100 randomized controlled clinical trials of prophylaxis against venous thromboembolism has been analysed. The purpose of this talk is to provide an overview of the currently available prophylactic methods analysed in these surveys, with an aim to define a policy for preventing venous thromboembolism, with particular emphasis on the surgical patients. There is evidence suggesting that the frequency of fatal pulmonary embolism can be reduced by such prophylactic remedies as low-dose heparin, dextran, the combination of dihydroergotamine plus heparin, and low molecular weight heparin. PMID- 3332109 TI - Cobalamin and folate metabolism in helminths. AB - Knowledge about the source, metabolism and functions of cobalamins and folates in helminths remains fragmentary. It is likely that all helminths, whether free living or parasitic, cannot synthesize cobalamins and folates de novo. Folates, but not cobalamins, appear to be ubiquitous in helminths. Of the parasitic helminths that take up free cobalamins in vitro, all but one species showed no uptake of cobalamin bound to transport proteins, although the latter type of cobalamin by far predominates in vivo. Certain free-living and parasitic helminths in vitro and in vivo took up a variety of folyl and antifolyl monoglutamates, but it is not known whether helminths can take up any folyl polyglutamates. Helminths that have any folate-dependent metabolism appear able to produce polyglutamylated forms of the required tetrahydrofolate coenzymes. Helminths that possess a functional cobalamin-dependent pathway from succinyl CoA to propionyl CoA appear able to form the required adenosylcobalamin coenzyme. Only free-living helminths may possess a cobalamin (and 5-methyltetrahydrofolate) dependent pathway from homocysteine to methionine. It is likely that all helminths possess the 5,10-methylenetetrahydrofolate-dependent pathway from deoxyuridylate to thymidylate. All helminths appear able to salvage purine bases and nucleosides, but 10-formyltetrahydrofolate-dependent de novo purine ribonucleotide synthesis has been demonstrated unequivocally only in nematodes. The primitive parasitic groups of helminths exhibit cobalamin metabolism, whereas the more highly evolved ones seem to have lost the mechanisms for uptake and the associated biochemical pathways utilizing cobalamins. PMID- 3332110 TI - Interleukin 2 and its receptor: structure, function and therapeutic potential. AB - In this review, salient molecular, biochemical and functional features of human interleukin 2 (IL-2), its membrane receptor, and its clinical relevance are outlined. We also describe experimental systems, where observed biological or pharmacological effects of IL-2 could be applied to corresponding clinical situations. In particular, IL-2 has been intensively studied in the context of cancer therapy. We discuss the rationale for the use of IL-2 in cancer treatment and our experience in this area. A better understanding of the IL-2 system and, specifically, the nature of signals transduced through it will allow us to manipulate the immune response in a variety of different ways, resulting in new approaches to investigation of immune responsiveness in general. This may have a profound impact on clinical medicine. PMID- 3332111 TI - Intestinal regulation of body iron. AB - A significant proportion of the world's population suffers from iron deficiency or iron overload. These disorders arise primarily from defects in the gastrointestinal absorption of iron. The intestinal mucosal cell plays a key role in this process because it lies at the interface between the gastrointestinal lumen which supplies its iron and body compartments which control its behaviour. The concentration of mucosal ferritin is closely linked to absorption, but it is still not clear whether it plays an active or a passive role. Transferrin also has been detected in the mucosal cell, but firm evidence that it participates in the absorptive process is lacking. Deficiencies in the luminal phase are responsible for the high global prevalence of iron deficiency which is predominantly dietary in origin. Much information has accumulated in recent years on dietary factors that enhance or impair iron absorption but their quantitative importance as determinants of iron status remains to be determined. PMID- 3332113 TI - How to diagnose (and not misdiagnose) pernicious anaemia. AB - The diagnosis of pernicious anaemia requires the demonstration that megaloblastic haemopoiesis is present, that vitamin B12 deficiency is present and that gastric intrinsic factor is lacking. The first, generally requires marrow aspiration, the second is satisfied by a low serum B12 level and the third by B12 absorption tests with and without intrinsic factor. The reasons why these three criteria are the minimum criteria for diagnosis are discussed as well as pitfalls in the performance of tests and in interpretation of data. Finally, a low serum vitamin B12 with impaired B12 absorption improved by the addition of intrinsic factor in the absence of blood changes indicates severe atrophic gastritis but not pernicious anaemia. PMID- 3332112 TI - Thalassaemia intermedia. AB - Most patients homozygous for beta thalassaemia have beta thalassaemia major, a severe illness requiring regular blood transfusions. However, some homozygotes remain well without regular transfusions and are described by the term thalassaemia intermedia. Three factors have now been identified which may result in beta thalassaemia intermedia: the inheritance of mild beta+ thalassaemia mutations, the co-inheritance of alpha thalassaemia and the inheritance of factors enhancing gamma-globin gene expression. In addition other less common genetic interactions also result in thalassaemia intermedia such as the compound heterozygous state for beta and delta beta thalassaemia. These patients need careful clinical follow up, especially since the complications of hypersplenism and iron overload (even in the absence of blood transfusion) can occur. PMID- 3332114 TI - Bone marrow transplantation in thalassaemia. PMID- 3332115 TI - Bone marrow transplantation in multiple myeloma: current status and future perspectives. PMID- 3332117 TI - Analysis of bone marrow transplantation data in man. AB - The use of bone marrow transplantation has increased rapidly since 1970; more than 2500 transplants will be performed in 1986. In this review I consider alternative approaches to analysis of data of bone marrow transplantation in man. The advantages and limitations of single-centre and pooled data analyses are considered. I suggest that both are needed and are complementary. Finally, I review the activities of the International Bone Marrow Transplant Registry and indicate future directions for collaborative research. PMID- 3332116 TI - Second marrow infusion for poor graft function after allogeneic marrow transplantation. AB - Fifty-seven patients undergoing allogeneic marrow transplantation had persistent poor graft function after transplant and received a second marrow infusion from the original donor. Eight donors were HLA-non-identical family members and 49 were HLA-identical siblings. Poor function of the initial graft occurred in the absence of demonstrable rejection or persistent malignancy. Preparative reconditioning was not given before the second marrow infusion. Thirty-four of the 57 patients survived more than 1 month after the boost and were evaluated for haematopoietic recovery. All 34 subsequently achieved a neutrophil count of more than 500 X 10(6)/l and 20 became independent of platelet transfusions. Forty-nine (86%) of the 57 patients demonstrated acute graft-versus-host disease (GVHD). In 24 of the 49 patients GVHD increased in severity (10 patients) or first appeared (14 patients) after the boost. Chronic GVHD developed in all of the 20 patients who survived more than 150 days after the second infusion. Currently, 10 patients survive (median follow-up of more than 5 years) and all have normal haematologic function. Although haematologic reconstitution and increased GVHD occurred in some patients receiving second marrow infusions, the relation of these outcomes to the marrow boost is unclear in the absence of a control group. PMID- 3332118 TI - Allogeneic bone marrow transplantation for adult leukaemia with soy bean lectin fractionated marrow. AB - A heterogeneous group of 11 consecutive patients with leukaemia have been transplanted successfully with allogeneic marrow depleted of T lymphocytes by soy bean lectin agglutination and neuraminidase-treated sheep erythrocyte rosetting. Effective depletion was achieved, leaving less than 1% of donor T lymphocytes. Despite the small numbers of nucleated cells infused (mean 0.14 X 10(8)/kg) there was only moderately delayed recovery of peripheral blood counts and no graft failures have occurred. Standard methotrexate prophylaxis against graft-versus host disease (GVHD) was also employed in the first four transplants. Only one case of mild grade I (skin only) acute GVHD has occurred and there has been no chronic GVHD to date. The group of patients show an actuarial cumulative survival of 55% with two early infective deaths (days 42 and 44 post-transplant) and three late deaths, two with leukaemic relapse and the third with probable viral encephalitis. The longest survivor is now 1109 days post-transplant. This series indicates that lectin fractionation of donor marrow, previously employed mainly in children, can also be effective in minimizing GVHD in adults without endangering successful engraftment. PMID- 3332119 TI - A randomized trial comparing use of cyclosporin and methotrexate for graft-versus host disease prophylaxis in bone marrow transplant recipients with haematological malignancies. AB - Patients with haematological malignancies with HLA-identical marrow donors were randomized to treatment with cyclosporin (CSA) or methotrexate (MTX). Two of the 29 patients randomized to MTX died before engraftment compared with none of the 30 treated with CSA. Engraftment by leucocytes (P less than 0.0001), granulocytes (P less than 0.02), and reticulocytes (P less than 0.01) was faster among the CSA patients. There were no significant differences between the two groups regarding transfusions, hospitalization and incidence of early septicaemia. Granulocyte transfusions were required in seven of 29 MTX and two of 30 CSA patients (not significant: NS). Overall (grade I-IV) acute graft-versus-host disease (GVHD) was more common (P = 0.001) in the CSA patients. Grade II-IV acute GVHD was seen in 40% of the CSA patients compared with 22% in the MTX patients (NS). In the adult patients grade II-IV GVHD was slightly more common (P less than 0.05) in those treated with CSA compared with MTX. Chronic GVHD appeared in 30 and 39% in the two groups respectively. Actuarial 3-year survival was 58% for the CSA patients and 69% for the MTX patients. There were no significant differences regarding the incidence of interstitial pneumonitis or relapses between the two groups. The side-effects of CSA treatment includes nephrotoxicity (83%), hepatotoxicity (20%), hirsutism (43%), hypertension (23%), tremor (27%) and gingival hyperplasia (27%). Serum creatinine values were increased at 3 and 6 months in the CSA group but were within the normal range after 6 months. A blind study on oral side effects revealed that CSA patients more often had a normal mucosa (P = 0.025) and less frequently had mucositis (P = 0.01) compared with the MTX group. PMID- 3332121 TI - Toxoplasma infection after human allogeneic bone marrow transplantation: clinical and serological study of 80 patients. AB - Systematic clinical and serological studies to evaluate the frequency of toxoplasmosis in bone marrow transplant recipients were performed in 80 consecutive patients. Antitoxoplasma antibody titres were measured in donors and recipients before transplant and subsequently post-transplant. Before bone marrow transplant, 54 recipients were seropositive and 26 were seronegative, whereas 35 donors were seropositive and 45 were seronegative. After bone marrow transplant, the frequency of clinical and serological manifestations of toxoplasmosis appeared closely related to the recipient's serological status before transplant. In the seronegative group of patients before transplant the incidence of toxoplasmosis was low: only two patients experienced seroconversion 3 months after bone marrow transplant and one developed clinical symptoms consistent with toxoplasmosis but without cerebral involvement. Clinical toxoplasmosis or secondary elevation of antibody titres was mostly observed in pre-bone marrow transplant seropositive patients; in this group, cerebral toxoplasmosis occurred in four patients and a significant secondary rise of antibody titres was observed in 16 patients. It thus appears that toxoplasmosis is most often related to a reactivation of latent cysts. Prophylactic treatment may be useful in patients presenting serological evidence of past or latent infection before bone marrow transplant. PMID- 3332120 TI - Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse. AB - Between December 1983 and November 1985 we treated 39 patients with chronic myeloid leukaemia by chemoradiotherapy and transplantation from HLA-identical sibling donors using bone marrow that had been depleted of T cells ex vivo with the rat monoclonal antibody Campath-1. Twenty-eight of the patients were in the chronic phase (good-risk group) and 11 patients were in more advanced phases of the disease (accelerated phase or blastic transformation; poor-risk group). Of the patients of good risk 23 (82%) survive; the median duration of follow-up is 461 (range 111-776) days; of the 11 patients of poor risk four survive; the median duration of follow-up is 280 (range 189-658) days. Acute graft-versus-host disease (GVHD) of grade II or greater occurred in three (11%) of the patients of good risk and in six (55%) of the patients of poor risk. In the patients of good risk haematological evidence of relapse was seen in four and cytogenetic evidence of persisting or relapsed leukaemia (based on the finding of Philadelphia chromosome-positive marrow metaphases more than 6 months after transplant) was seen in three other patients. In comparison with the patients of good risk transplanted with untreated marrow between February 1981 and December 1983, the incidence of acute GVHD was reduced significantly (P less than 0.001) but the risk of leukaemic relapse (including patients with only cytogenetic evidence of relapse) was increased (P less than 0.005). We conclude that T-cell depletion used in this manner may be associated with an increased risk of leukaemic relapse. PMID- 3332122 TI - Allogeneic bone marrow transplantation versus chemotherapy for childhood acute lymphoblastic leukaemia in second remission. AB - Thirty-six children with acute lymphoblastic leukaemia (ALL) in second remission were treated with conventional chemotherapy or with cyclophosphamide and fractionated total-body irradiation followed by an allogeneic bone marrow transplant; the choice of treatment was dictated by the availability of an HLA identical sibling. The age, sex, clinical data at presentation of the disease and duration of first remission were comparable for the two groups of patients. In the bone marrow transplantation group two patients died of graft-versus-host disease and five of leukaemia. Ten patients survive, nine disease free, 13-53 months from second remission (6-51 months post-bone marrow transplantation). In the chemotherapy group 14 patients died of leukaemia (2-29 months from second remission) and five survive (22-34 months from second remission). The actuarial survival for patients with bone marrow transplantation is 48% at 4 years as compared with 22% for those of the chemotherapy group (P = 0.04); the actuarial probabilities of being in remission are 58 and 18% in the two groups respectively (P = 0.01). This study confirms that allogeneic bone marrow transplantation is superior to chemotherapy in patients in second remission with ALL and should be considered in the presence of an HLA-identical sibling. PMID- 3332123 TI - Marrow transplantation for non-Hodgkin's lymphoma: a multi-centre study from the European Co-operative Bone Marrow Transplant Group. AB - Twenty-five patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) were treated by allogeneic bone marrow transplantation. For the nine patients transplanted in first complete remission the disease-free survival was 100%; of the nine patients transplanted in subsequent remissions four (44%) achieved long-term disease-free survival but two died of relapsed lymphoma. For the seven patients transplanted at a time when they had active disease, the initial complete remission rate was high but four died of progressive lymphoma and no patient achieved long-term disease-free survival. The incidence of complications associated with allogeneic bone marrow transplantation was similar to that observed in other series of patients transplanted for haematological malignancy and was related to the status of the disease at the time of transplant. Thus allogeneic bone marrow transplantation is a radical but effective treatment for patients with NHL who have 'minimal residual disease'. Efforts to define further the subset of patients who can most successfully be treated by transplantation may improve the overall results. PMID- 3332124 TI - Is race a risk factor for allogeneic marrow transplantation? AB - We investigated the influence of race as a risk factor for the outcome of HLA identical marrow transplantation. The actuarial survival at 2 years after grafting of Blacks, Hispanics and Asians was compared with that of Caucasians transplanted between 1971 and 1985 for aplastic anaemia, acute non-lymphocytic leukaemia and acute lymphoblastic leukaemia. Among patients with aplastic anaemia, there was no difference with regard to engraftment or actuarial survival among different racial groups. Among patients with acute non-lymphocytic leukaemia, Blacks had a lower survival (P = 0.03) than other groups, although there was no obvious single factor accounting for this difference. In patients with acute lymphocytic leukaemia, survival was comparable among the different races. Acute and chronic graft-versus-host disease appeared to occur with similar frequencies in all groups, except for a slightly higher incidence among Blacks with acute non-lymphocytic leukaemia. Larger numbers of patients need to be examined before firm conclusions can be drawn. PMID- 3332126 TI - The decision in pediatrics to go ahead with bone marrow transplant for a pediatric malignancy. AB - Bone marrow transplantation in pediatrics has become an accepted modality of therapy for a variety of malignant diseases. This sophisticated approach is now being used worldwide in a large number of centers for children who fail to respond to conventional therapy. In this review I have addressed the questions of when we should offer a bone marrow transplant, what medical issues impact on this decision, when such treatment is in the child's best interests and who acts for the patient during the transplant procedure. The decision to proceed with a bone marrow transplant is a complex one and requires frank discussions on a regular basis between family members and professional staff since, for many of these questions, there are no set responses. PMID- 3332125 TI - Appearance of an inherited porphyria cutanea tarda in a child after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. AB - We report details of a 6 1/2-year-old girl who developed porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. The results of studying porphyrin metabolism in the family members are described. Expression of the disease may have been induced by the cyclophosphamide and total body irradiation in the conditioning regimen and/or by the administration of methotrexate for the prevention of graft-versus-host disease and meningeal leukaemia. PMID- 3332128 TI - Graft-versus-host disease following transplantation of 'one log' versus 'two log' T-lymphocyte-depleted bone marrow from HLA-identical donors. AB - Prevention of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation, requires the depletion of mature T-lymphocytes from bone marrow grafts. The optimal degree of T-cell reduction is still an open question. We compared two procedures of T-cell separation in 18 consecutive recipients of genotypically HLA-matched bone marrow, who also received cyclosporin A for 6 months. The first method (A) was based on a discontinuous albumin gradient fractionation and resulted in an average T-lymphocyte content of 50 X 10(5)/kg body weight (n = 9 patients); the second method (B) was based on E-rosette sedimentation and reduced the contamination to 15 X 10(4) grafted T lymphocytes/kg body weight on the average (n = 9 patients). Thus, approximately 90 and 99% of the original T-lymphocytes were removed from the marrow grafts respectively. Of the seven patients of the first group who were at risk of GVHD (excluding two cases of early death), five developed a minimal-to-moderately severe acute GVHD and in two cases chronic GVHD ensued. Lethal GVHD was not seen. Of group B, all recipients engrafted and none developed GVHD (0/9). The difference in the frequency of GVHD between the two groups was highly significant (P less than 0.0025). These data confirm our preclinical studies. They demonstrate that a one-log T-lymphocyte reduction of the marrow inoculum, when combined with cyclosporin A prophylaxis after major histocompatibility complex (MHC)-matched transplantation, is still associated with a considerable incidence of GVHD, whereas a two-log reduction of T-lymphocytes may provide full protection against acute GVHD. PMID- 3332127 TI - Marrow transplantation for thalassemia. AB - Ten patients with homozygous beta thalassemia, aged from 1 year 7 months to 13 years, underwent bone marrow transplantation from siblings or parents. The first case received 12 mg/kg busulfan, 120 mg/kg cyclophosphamide, and 300 cGy total body irradiation before transplantation; he survives, with a graft, more than 680 days after transplantation. The other nine patients received 16 mg/kg busulfan and 200 mg/kg cyclophosphamide. Two died of transplantation-related complications on days 30 and 55. Seven survive 170 to 580 days after transplantation. Three of the seven surviving patients have durable engraftment (greater than 230 to greater than 550 days) while four patients have autologous hematopoietic recovery. Four of five patients who had less than 50 prior transfusions achieved engraftment. Only one of five patients who had more than 50 prior transfusions achieved engraftment (P less than 0.05). The six-month actuarial survival was 80%; six-month actuarial disease-free survival was 40%. These data demonstrate that bone marrow transplantation may cure thalassemia, but engraftment may be jeopardized among patients who have been heavily transfused or have received marrow from a donor who is not HLA-identical. PMID- 3332129 TI - Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation. AB - Seventy-five patients with acute nonlymphoblastic leukemia (ANL) in first remission were treated with cyclophosphamide, 60 mg/kg on each of two consecutive days followed by total body irradiation (TBI) at an exposure rate of 4-6 cGy/min from two opposing 60Co sources. The first 22 patients were given 9.2 Gy of TBI as a single dose. Subsequently 53 patients were randomized to receive either 10 Gy single dose TBI (n = 27) or 6 x 2 Gy fractionated TBI (n = 26). All patients received marrow transplants from HLA-identical siblings and all had sustained engraftment. Patients given 10 Gy of TBI had more early toxicity, especially veno occlusive disease of the liver, than patients given 9.2 or 6 x 2 Gy of TBI. Idiopathic interstitial pneumonitis appeared to be more frequent in patients given 9.2 or 10 Gy single-dose TBI than in patients given 6 x 2 Gy fractionated TBI. Patients have now been followed from 5 to 9 years. Survival (+/- 95% confidence limits) at 5 years is 54 +/- 31% among patients given 9.2 Gy single dose TBI, 33 +/- 31% among patients given 10 Gy single dose TBI, and 54 +/- 26% among patients given 6 x 2 Gy fractionated TBI (P = 0.04). These results indicate that about half the patients with ANL transplanted while in first chemotherapy induced remission can be expected to become long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332130 TI - Second marrow transplants for recurrence of haematological malignancy. AB - Nine patients with haematological malignancy relapsed 3-32 months after receiving cyclophosphamide 120 mg/kg, 12-14 Gy fractionated total body irradiation and an HLA-identical sibling bone marrow transplant. They were reconditioned with melphalan 180-220 mg/m2 and retransplanted using the same donor and the same cyclosporin regimen as prophylaxis for graft-versus-host disease (GVHD). Three of the nine remain alive greater than 81, greater than 33, and greater than 36 months after second transplant. While the rate of marrow engraftment, the incidence of acute GVHD and the incidence of interstitial pneumonitis were similar after first and second transplants, the use of melphalan before second transplant was associated with increased nephrotoxicity and oropharyngeal mucositis. The present study shows that second narrow transplants are feasible, can produce prolonged remission of haematological malignancies and should be considered in appropriate patients who relapse after first marrow transplant. PMID- 3332131 TI - Prevention of graft-versus-host disease by immunosuppressive agents after transplantation of DLA-nonidentical canine marrow. AB - Dogs given 9.2 Gy of total body irradiation (TBI) followed by hematopoietic grafts from DLA-nonidentical unrelated or littermate donors and no postgrafting immunosuppression all develop acute graft-versus host disease (GVHD) and die within 3 weeks of grafting. Over a period of 10 years, the present study evaluated various immunosuppressive drugs either alone or in combination and compared their effectiveness to that of methotrexate (MTX) in preventing acute GVHD and prolonging survival. Among the single agents tested, 6-mercaptopurine and azathioprine resulted in a slight but significant prolongation of survival compared to controls, but they were less effective than MTX. Procarbazine and cytosine arabinoside were ineffective. Drugs tested in combination included MTX, cyclophosphamide, 6-mercaptopurine, azathioprine, cyclosporin, procarbazine, prednisone and antithymocyte globulin. Drug combinations, while effective in delaying the onset of GVHD, were associated with hematopoietic and other toxicities, which made their use impractical. Administration of MTX twice weekly proved to be no better than once weekly administration. Prednisone administered for the first 4 days after grafting in addition to MTX resulted in a modest improvement in survival. High-dose MTX (200 mg/kg) followed by leukovorin rescue resulted in severe early toxicity, both gastrointestinal and hematopoietic; however, some of those dogs which survived the early postgrafting period became stable long-term survivors. Most single agents tested in the present study proved to be either ineffective or were inferior to MTX in their ability to prevent GVHD. None of the drug combinations tested was as effective as the one involving MTX/cyclosporin reported previously. PMID- 3332132 TI - Busulphan and cyclophosphamide cause little early toxicity during displacement bone marrow transplantation in fifty children. AB - Fifty children were induced with busulphan and cyclophosphamide before bone marrow transplantation. Our standard dose of cyclophosphamide was 2 g/m2 daily for 4 days, but this dosage was reduced if necessary so as not to exceed 75 mg/kg/day. A basal pulse rate that increased by more than 20 beats/min or a reduction in ECG voltage were indications for stopping cyclophosphamide. As a consequence, the fourth dose of cyclophosphamide was omitted for four children. One child died of cardiac arrest related to cyclophosphamide. We used busulphan at a dosage of 4 mg/kg/day for 4 days; neither 'busulphan lung' nor veno occlusive disease occurred in any patient. The use of busulphan and cyclophosphamide did not guarantee freedom from interstitial pneumonitis, but this seemed to be related rather to the nature of prior treatment and the cytomegalovirus antibody status of the patient. Thus, we have developed a safe chemotherapy schedule for transplantation that avoids the need for radiotherapy and can, if necessary, be repeated after a 3-month interval. PMID- 3332133 TI - Normal blast colony formation: an in vitro tool for monitoring human bone marrow 'purging'. AB - A major problem in autologous bone marrow transplantation is that it is impossible to evaluate in vitro the effect of drug treatment on haematopoiesis. However, Gordon and colleagues have recently established a colony forming assay which detects very immature blast progenitor cells. This method can be used to measure the myelotoxicity of drugs used for removing malignant cells from bone marrow ('purging') before autografting and we have analysed the action of mafosfamide on normal blast colony formation. Treatment in vitro with mafosfamide did not impair the formation of blast colonies containing very primitive cells (type I) but suppressed the formation of the colonies of more mature cells (types II and III) which grow under the same culture conditions. The surviving type I blast colony-forming cells were capable of self-renewal and differentiation. In contrast granulocyte-macrophage colony-forming units (GM-CFU) were totally destroyed by treatment with mafosfamide. PMID- 3332135 TI - Gene therapy using bone marrow transplantation. AB - As a result of new techniques in molecular biology, the basic defects in a variety of genetic diseases have been characterized and the corresponding normal genes cloned. Methods have been devised for transferring specific genes with high efficiency into various cell types that exploit the use of replication-defective retroviruses as vectors. Bone marrow may be the ideal target for these attempts to transfer genes, because it contains self-renewing stem cells and because it can readily be collected by standard techniques, manipulated ex vivo as required with comparative ease and then reinfused. In a murine system, recent studies have shown that genes can indeed be incorporated into haemopoietic stem cells that can then completely reconstitute the marrows of syngeneic recipients. Thus far, such genes after transfer have not been appropriately expressed in vivo, although appreciable expression has been documented in cell culture studies in vitro. It is reasonable to expect that improvements in the design of retroviral vectors should permit appropriate expression of a transferred gene. When this is achieved, the use of bone marrow transplantation for gene transfer will offer new options for therapy. PMID- 3332134 TI - Prolonged remission of severe refractory rheumatoid arthritis following allogeneic bone marrow transplantation for drug-induced aplastic anaemia. AB - Aplastic anaemia developed in a 33-year-old woman whose rheumatoid arthritis was refractory to the administration of many drugs, including penicillamine and gold. Allogeneic bone marrow transplantation reversed the haematological abnormality and simultaneously resulted in a 2-year period of relief from joint pain. Symptoms then reappeared and the serological tests for rheumatoid arthritis again became positive. The arthralgia has responded slowly to the administration of anti-inflammatory drugs and steroids. The protracted asymptomatic period may have been due to the intense immunosuppression required for marrow grafting and the subsequent administration of cyclosporin. Since she developed chronic graft versus-host disease, the arthritis may be an unusual complication of this syndrome. PMID- 3332136 TI - Histocompatible unrelated donors for bone marrow transplantation. AB - Bone marrow transplantation using HLA one haplotype mismatched family donors has been associated with a high incidence of severe graft-versus-host disease, and an increased risk of graft failure. Recently, the use of histocompatible unrelated donors has been investigated when an HLA genotypically identical sibling is not available. Conventional histocompatibility testing of potential unrelated donors does not always predict alloreactivity in vivo. In this review, the preliminary results of histocompatible unrelated transplants are presented and methods of matching unrelated donors discussed. PMID- 3332137 TI - Cyclosporin in bone marrow transplantation. AB - Cyclosporin, the first truly selective immunosuppressive agent, has a useful role in HLA-identical sibling bone marrow transplantation for haematological malignancy and severe aplastic anaemia. Specifically, it has been shown to minimise graft-versus-host disease, particularly when used in combination with methotrexate, and to reduce the risk of marrow graft rejection. Its mode of action, pharmacology, clinical utility and toxicology in the marrow transplant setting are described. PMID- 3332138 TI - Autologous bone marrow transplantation for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia--a comparison. AB - Forty-two patients with acute leukaemia were treated with autologous bone marrow transplantation (ABMT) using a combination chemotherapy protocol for bone marrow ablation. The response to high-dose chemotherapy and ABMT and its associated morbidity and mortality have been compared in 24 patients with acute myeloid leukaemia (AML) and 18 patients with acute lymphoblastic leukaemia (ALL). In 16 patients with AML treated with ABMT during first complete remission (CR), ten patients (62.5%) remain in unmaintained remission; median follow up is 32 months. In eight patients with ALL treated in first CR, only one remains in remission 32 months post-ABMT, with three patients dying non-leukaemic deaths. Fourteen of 18 patients (AML and ALL) treated after first remission have died of recurrent leukaemia, two died non-leukaemic deaths and two remain well 31 and 55 months post-ABMT; both have ALL. The length of hospital stay and the amount of blood product support were similar in both groups. Haematological recovery post-ABMT was delayed in patients with AML compared to patients with ALL but this difference was not significant. Rapidly progressive lung infection was thought to be the cause of four early deaths (4/18) in patients with ALL but none in patients with AML. Severe gram-negative infections were significantly more common in patients with AML. PMID- 3332139 TI - Monitoring cyclosporin concentrations in marrow transplant recipients: comparison of two assay methods. AB - Renal dysfunction is the major dose-limiting toxicity associated with cyclosporin therapy. We have previously shown in patients undergoing allogeneic bone marrow transplantation that serum cyclosporin concentrations, as measured by radioimmunoassay (RIA), correlate significantly with the development of renal dysfunction. However, since the RIA measures both parent drug and metabolites, the relative role of each in the development of nephrotoxicity could not be determined. Therefore, we re-measured cyclosporin concentrations in the same serum samples by high-performance liquid chromatography (h.p.l.c.). Serum cyclosporin concentrations of less than 50, 50-100 and greater than 100 ng/ml, as measured by h.p.l.c., were considered equivalent to cyclosporin concentrations of less than 150, 150-250 and greater than 250 ng/ml, as measured by RIA. Contrary to results by RIA, cyclosporin concentrations measured by h.p.l.c. did not significantly correlate with renal dysfunction, which suggests that measurement of serum cyclosporin concentrations by h.p.l.c. provides no clinical advantage to RIA for monitoring cyclosporin concentrations to prevent renal dysfunction. PMID- 3332140 TI - Evaluation of a monoclonal IgM antibody for purging of bone marrow for autologous transplantation. AB - A monoclonal antibody of the IgM class, reacting with the CD9 (p24) antigen is described. The antibody (FMC27) is cytotoxic against cells of the common type of acute lymphoblastic leukaemia (c-ALL), giving killing at higher dilutions than an IgG antibody (FMC8) against the same antigen. FMC27 and FMC8 recognise different epitopes, and FMC27 may thus be used in a cocktail together with FMC8 and an antibody against the c-ALL antigen, WM21. Furthermore, the IgM antibody can be coated directly onto magnetic microparticles for magnetic purging, unlike the IgG antibody which must be used in a two-layer procedure. PMID- 3332141 TI - Immunological recovery after bone marrow transplantation: role of age, graft versus-host disease, prednisolone treatment and infections. AB - Cellular immune recovery was studied in 67 patients who had survived for one month to more than 6 years after bone marrow transplantation (BMT). From a number of immunological parameters the mitogens phytohemagglutinin, concanavalin A and rabbit antibodies to beta 2 microglobulin (A-beta 2m) were chosen because of relevant increases in lymphocyte responses with time after BMT for analysis with exponential functions (covariance analysis). Patients with younger donors had a markedly higher lymphocyte response level and a faster rate of increase with time than patients with older donors. High recipient age was also significantly associated with a depressed level of immunological response but to a lesser degree than donor age. Patients with chronic graft-versus-host disease (GVHD) had a more severely impaired response compared to patients without chronic GVHD. Furthermore, patients with GVHD showed a negative development over time with the A-beta 2m test. Lymphocytes from patients receiving a low donor marrow cell dose showed impaired response levels and rate of recovery compared to the high-dose group although the differences were not significant. Patients treated with prednisolone for grade I GVHD had depressed lymphocyte stimulations for up to 1 1/2 years post BMT compared to patients without GVHD and not receiving prednisolone. Patients with non-viral infections seemed to have more depressed lymphocyte responses than non-infected patients. Patients undergoing cytomegalovirus infections had lower response levels for all three mitogens. PMID- 3332142 TI - Allogeneic and syngeneic marrow transplantation following high dose dimethylbusulfan, cyclophosphamide and total body irradiation. AB - Fifty-eight patients received an allogeneic or syngeneic marrow transplant following conditioning with high doses of dimethylbusulfan (DMB), cyclophosphamide (CY) and total body irradiation (TBI). Thirty-two patients had either chronic myeloid leukemia (CML) in accelerated phase or blast transformation, or acute leukemia after first relapse. The actuarial survival of these 32 patients at 3 years was 12% compared with 25% for a group of 206 patients with similar diagnoses prepared for transplantation with CY and TBI alone. This reduced survival was associated with a greater incidence of early non leukemic deaths, in particular as a result of severe hepatic veno-occlusive disease. The incidence of leukemic relapse was not different in the two groups. Of 13 patients with CML in chronic phase who received syngeneic transplants following DMB, CY and TBI, nine are alive in hematologic and cytogenetic remission from 3.9 to 9.4 (median 6.2) years post-transplant. PMID- 3332143 TI - Purging breast cancer cells in preparation for autologous bone marrow transplantation. AB - Mixtures of the T-47D human breast cancer cell line and normal human bone marrow cells were used for studying a new approach for purging epithelial tumor cells for autologous bone marrow transplantation (BMT) in breast cancer. Breast cancer cell line T-47D cells were shown to bind soybean agglutinin (SBA) in a specific fashion that could be blocked by D-galactose. Tumor cells were effectively purged by both SBA agglutination and depletion of cells bound to magnetic beads (0.7-5.0 micron) covalently linked to SBA. A depletion of 3-4 orders of magnitude of tumor cells was consistently accomplished by combining one step of agglutination followed by one cycle of SBA-magnetic bead depletion. Neither procedure affects stem cell recovery. We suggest that effective purging of breast cancer cells can be accomplished using SBA for autologous BMT in patients with advanced breast cancer. PMID- 3332144 TI - Treatment of marrow graft recipients with thymopentin. AB - Four adult patients with acute non-lymphocytic leukemia were given marrow grafts from HLA-identical siblings following 120 mg/kg cyclophosphamide and 10-12 Gy total body irradiation. All received intermittent intravenous methotrexate as prophylaxis against graft-versus-disease (GVHD). In an attempt to accelerate immune recovery and prevent GVHD, each patient received thymopentin (TP5) for 100 days after grafting. No adverse effects were seen with TP5 administration. All four patients developed acute GVHD (one grade I, one grade II, and two grade III). Two patients died of late infections: one at 6 months from Pneumocystis carinii pneumonia and one at 11 months from disseminate Pseudomonas, Candida and cytomegalovirus infection. Two patients survive more than 3.9 years after transplantation with Karnofsky scores of 100%. One required treatment for chronic GVHD and recovered. Delayed-type hypersensitivity, antibody production to specific antigen in vivo, and results of in vitro immunologic studies were not altered by TP5 treatment. We conclude that while the administration of TP5 in these patients as described was not harmful, it did not prevent opportunistic infection, improve immunologic reconstitution or lower the incidences of acute or chronic GVHD from that of our previous experiences without thymopentin. PMID- 3332145 TI - Early leukemic recurrence of non-Hodgkin lymphoma after high-dose anti-neoplastic therapy with autologous marrow rescue. AB - Five patients with recurrent non-Hodgkin lymphoma treated with high-dose salvage anti-neoplastic therapy supported by unpurged histologically uninvolved autologous bone marrow reinfusion have suffered relapse in the blood and bone marrow within a few weeks of the marrow reinfusion. Four of these patients had the small non-cleaved (Burkitt) sub-type of malignant lymphoma. Additional risk factors for such 'leukemic relapse' appear to include a rapid clinical course prior to the salvage therapy and the presence of karyotypic subclones within the malignant cell population. It seems likely that these relapses occurred as a result of reinfusion of small numbers of viable 'marrow homing' malignant cells with the autologous bone marrow. This pattern of recurrence is rare in patients with other lymphoma sub-types receiving unpurged marrow. These data may permit exclusion of patients at high risk for this devastating relapse pattern from clinical trials of unpurged autologous marrow transplantation and the selection of patients for trials of marrow purging. PMID- 3332146 TI - Modification of the sponge allograft model to study the immune response to bone marrow cells. AB - The sponge allograft model of Roberts & Hayry and of Ascher et al. was modified by introducing bone marrow cells into uncoated sponges 7 days after the sponge was implanted into the mouse. The number and cellular composition of the response in the sponges was essentially the same whether the stimulus was allogeneic or syngeneic bone marrow. However, the allogeneically stimulated sponge derived cells demonstrated allospecific cell-mediated lympholysis at very low effector-to target ratios. Similar cytotoxic activity was difficult to demonstrate in splenic cells from the same animal tested concurrently. The cytotoxic cells were shown to be Lyt-1-, 2+ and Thy 1+. For a bone marrow impregnated sponge the peak T cell killing was reached after 12 days whereas peak killing occurred on day 14 in peritoneal cell infiltrated sponges as utilized by Ascher et al. Our model was developed to study the response to various antigenic stimuli placed into the sponge. This variation of the sponge allograft model should permit the study of a local cellular immune response to a number of antigens. PMID- 3332147 TI - Study of a human minor alloantigen in relation to clinical graft-versus-host disease. AB - Sixty-seven pairs of HLA matched siblings, each comprising marrow donor and recipient in the Seattle marrow transplant program, were analyzed to establish phenotype for a newly described minor H antigen, W1. The test for phenotype entailed cold target inhibition of cytotoxicity, directed at this antigen and mediated by specifically stimulated T cell lines. There were 58 compatible and six W1 incompatible pairs. The low frequency of W1 mismatch is due to the strong preponderance of W1-positive individuals in the general population. Severe graft versus-host disease (GVHD), both acute and chronic, was observed among the 58 recipients of marrow from W1 matched donors. These results do not reveal any particular importance for W1 incompatibility in human GVHD and indeed indicate that other systems are involved. Even if some cases are triggered by incompatibility at W1, the maximum frequency with which this could occur would be about 10%, due to the limited polymorphism of this alloantigenic system. PMID- 3332149 TI - Subacute thyroiditis after bone marrow transplant for chronic granulocytic leukaemia. PMID- 3332150 TI - The role of bone marrow transplantation following nuclear accidents. AB - Hematopoietic stem cells are extremely sensitive to damage by ionizing radiation. At high doses of radiation, toxicity to the bone marrow may be operationally irreversible. Insufficient functional hematopoietic stem cells remain or irradiated individuals cannot survive sufficiently long enough for functional stem cell recovery. Both situations can be approached by bone marrow transplantation. This review considers the possible uses and limitations of bone marrow transplantation following nuclear accidents. PMID- 3332148 TI - Thymus and B cell reconstitution in severe combined immunodeficiency after transplantation of monoclonal antibody depleted parental mismatched bone marrow. AB - Two brothers were transplanted with bone marrow which was depleted of mature T cells with monoclonal antibody CT-2 plus complement. One child died of sepsis due to candida present prior to transplant. The other is alive and well with full T and B cell reconstitution over 36 months after transplant. Thymus biopsy taken after transplant demonstrated normal morphology and cellularity. Portions of the marrow that were radiolabeled permitted an assessment of traffic patterns of aliquots that were injected intravenously and directly into the marrow space. The studies reported here document that a one haplotype mismatch is not a sufficient disparity to preclude both B and T cell reconstitution, and that monoclonal antibody plus complement is an effective method for T cell depletion. PMID- 3332151 TI - Bone marrow transplantation for malignant histiocytosis. PMID- 3332152 TI - Intensive chemoradiotherapy and autologous bone marrow transplantation for resistant lymphoma. PMID- 3332153 TI - Harvesting marrow for autologous transplantation from patients with malignancies. AB - One hundred and sixty-six patients with malignancies had 170 consecutive bone marrow collection procedures in anticipation of autologous transplantation. The morbidity associated with these harvest procedures was increased compared to morbidity experienced by normal donors who had marrow collected for allogeneic transplantation when unexplained fever (p = 0.02) and infection (p = 0.008) were considered. No differences could be found in the characteristics of the harvested marrow including concentration of nucleated cells and nucleated cell content between the two donor groups. No deaths occurred as a result of the harvest procedure. However, a previously reported series of autologous marrow donors from a different institution did not demonstrate an increased morbidity associated with marrow harvesting when compared to the same series of normal donors. The differences found in the two autologous series might be explained by differing characteristics of the patient populations. The increased morbidity found in our patients was tolerable and reversible and not a contraindication to high-dose therapy with autologous bone marrow transplantation. PMID- 3332154 TI - Allogeneic bone marrow transplantation using partially-matched related donors. AB - Six patients with advanced leukemia and one with severe combined immunodeficiency syndrome received allogeneic bone marrow transplantation (BMT) from HLA haploidentical donors who were compatible for one or two loci on the non-shared chromosome. Methotrexate was used for prophylaxis against acute graft-versus-host disease (GVHD). All patients engrafted but developed moderate to severe acute GVHD, and three patients died. Two leukemic patients relapsed but two others survived and were free of disease 403 and 936 days post-transplant. BMT using related partially matched donors may result in durable engraftment and long-term survivors. The implications of using such donors in expanding the application of BMT are discussed. PMID- 3332155 TI - Difference in kinetics of hematopoietic reconstitution between ALL and ANLL after autologous bone marrow transplantation with marrow treated in vitro with mafosfamide (ASTA Z 7557). AB - The kinetics of hematopoietic recovery after autologous bone marrow transplantation (ABMT) reflect the hematopoietic capacity of the infused marrow. In vitro treatment of marrow with high doses of mafosfamide (ASTA Z 7557) alters the hematopoietic regenerative capacity of the graft. Thirty-two patients with acute leukemia (12 acute lymphoblastic leukemia (ALL) and 20 acute non lymphoblastic leukemia (ANLL] with 27 in complete remission and five in partial remission were consolidated with cyclophosphamide (60 mg/kg x 2) and total body irradiation (10 Gy), followed by reinfusion of autologous marrow treated in vitro with mafosfamide. The marrow of each patient had been incubated with the highest tolerable dose of mafosfamide, individually predetermined from a preincubation test. We report here that the kinetics of engraftment are strikingly different in ANLL and ALL patients. In the ANLL group recovery to 0.1% reticulocytes took a median of 20.5 days (range 14-32) versus 15 (11-28) in the ALL group; 33.5 days (18-45) versus 19 (15-30) for leukocytes to reach 1.0 x 10(9)/l; 35 (19-60) versus 20.5 (15-30) for neutrophils to reach 0.5 x 10(9)/l; 110+ (45-480+) versus 50 (23-90) for platelets to reach 50 x 10(9)/l (p less than 0.01 and p less than 0.05). Detection of granulocyte-macrophage progenitors (CFU-GM) regeneration in marrow aspirates post-ABMT was delayed in ANLL (p less than 0.05). Neither the nature of the previous induction therapy, nor the status of the blood or bone marrow at the time of collection (CFU-GM and erythroid burst-forming units/ml) nor the stem cell sensitivity to mafosfamide, nor the doses of progenitor cells infused could explain these differences. We interpreted these observations as suggesting that the engraftment potential has been more severely altered in ANLL than in ALL, which may reflect both the intensity of the in vitro treatment and the intrinsic fragility of the stem cell pool in ANLL. PMID- 3332157 TI - Human marrow T cell dose correlates with severity of subsequent acute graft versus-host disease. AB - Sixteen patients with haematological malignancy received high-dose chemotherapy or chemotherapy and total body irradiation followed by an HLA-identical sibling marrow transplant from which the T lymphocytes had been depleted prior to infusion by incubation with an anti-CD2 anti-T cell antibody with (seven patients) or without (nine patients) an anti-CD8 anti-T cell antibody together with rabbit complement. Additionally, all patients received cyclosporin. The number of T cells present in the donor marrow was determined by limiting dilution analysis, and was found to correlate with the subsequent incidence and severity of acute graft-versus-host disease (GVHD). The number of T cells infused into patients with no acute GVHD or with minimal acute GVHD of the skin (skin rash present for 14 days or less) was 1.3 +/- 1.0 x 10(5)/kg, while the number infused into those with moderate acute GVHD or with skin acute GVHD present for 15 days or more was 12.3 +/- 11.5 x 10(5)/kg (p less than 0.001). Thus a dose of 10(5) (or less) T cells/kg was associated with minimal or no acute GVHD, while 10(6) T cells/kg (or more) caused significant disease. PMID- 3332156 TI - Experience with marrow harvesting from donors less than two years of age. AB - Experience in harvesting marrow for allogeneic marrow transplantation from 23 infant donors is presented. Ten donors were less than one year of age and 13 were between one and two years of age at the time of initial donation. None of these donors experienced major difficulties following the aspiration procedure. Three donors had significant medical problems diagnosed during the pre-donation evaluation. All aspirations were performed from iliac crests and all donors were given general anesthesia. Irradiated blood bank transfusions were given to 85% of the donors during the procedure. The volume of marrow obtained ranged from 11.5 to 19.3 ml/kg donor weight and contained from 2.5 to 10.4 x 10(8) nucleated cells/kg donor weight. Thus, very young children may safely donate marrow for allogeneic transplantation and the nucleated cell count obtained is substantial. PMID- 3332158 TI - Experimental evaluation of an immunomagnetic bone marrow purging procedure using the Burkitt lymphoma model. AB - In order to test the numerous variable biological parameters which may contribute to the efficiency of the immunomagnetic depletion method, experiments have been carried out with different Burkitt lymphoma cell lines. The Hoechst dye method, a sensitive assay able to detect 3 log elimination, and a liquid culture assay suitable for identifying an elimination greater than 4 logs, were used to measure malignant cell elimination. These assays showed that the separation of bone marrow mononuclear cells on Ficoll-hypaque, the use of beads in excess, and a double treatment of the samples are needed to obtain optimal depletion of malignant cells. Under these conditions, the immunomagnetic procedure is capable of depleting 1% tumour cell infiltration at the lower limit of detection of a very sensitive culture assay (i.e. greater than 4 log elimination). PMID- 3332159 TI - Treatment of poor prognosis non-Hodgkin's lymphoma using cyclophosphamide and total body irradiation regimens with autologous bone marrow rescue. AB - Twenty patients with poor prognosis non-Hodgkin's lymphoma received regimens which employed cyclophosphamide and total body irradiation followed by autologous bone marrow rescue. There were two toxic deaths. All 10 patients with residual disease prior to treatment achieved a complete remission. Ten patients survive disease free from 1.4 to 9.5 years and median survival exceeds 2.9 years. The actuarial 3-year disease-free survival is 50%. Treatment with cyclophosphamide and total body irradiation followed by autologous bone marrow infusion is an effective salvage regimen for poor prognosis lymphoma. Durable long-term remissions can be achieved. PMID- 3332161 TI - Bone marrow transplantation for secondary (therapy-related) acute non lymphoblastic leukaemia: report of a case associated with adoptive beta thalassaemia. AB - A female patient with therapy-related acute non-lymphoblastic leukaemia occurring after intensive combined modality treatment for IIIB Hodgkin's disease was transplanted from her HLA-identical brother. No attempt was made to induce a remission and the transplant was performed with standard chemoradiotherapeutic conditioning. Three years after the transplant the patient is alive in complete remission with a 46,XY karyotype. The donor has a mild, heterozygous beta thalassaemia ('thalassaemia minima'). The recipient has much more pronounced thalassaemic features, similar to so-called thalassaemia intermedia, with peripheral blood smears indistinguishable from thalassaemia major. The erythrocytic alterations are undoubtedly due to the splenectomy which was performed during a staging procedure, but the marked difference between donor and recipient haemoglobin values cannot be attributed solely to the asplenic state. PMID- 3332160 TI - Bone marrow transplantation for advanced acute lymphoblastic leukemia in young people: a comparison of two conditioning regimens. PMID- 3332162 TI - Monoclonal antibodies and magnetic microspheres for the depletion of leukaemic cells from bone marrow harvested for autologous transplantation. AB - The use of a panel of monoclonal antibodies and anti-mouse immunoglobulin-coated microspheres is described for the depletion of leukaemic blasts from bone marrow. Marrow treated in this way rapidly reconstitutes haemopoietic function after high dose consolidation chemoradiotherapy. The recovery of cells from bone marrow is similar but not identical to results obtained on removal of neuroblasts from marrow to be used for autologous transplant. This is probably a reflection of the cross-reactivity of 'anti-leukaemic' antibodies with a variety of haemopoietic progenitor cells. The study described here demonstrates the feasibility of using this method to purge leukaemic cells from bone marrow. A much larger randomised study between patients receiving either purged or non-purged bone marrow would be necessary to validate the need to remove small numbers of tumour cells from bone marrow. PMID- 3332163 TI - Vim-2, candidate monoclonal antibody for purging autologous marrow grafts in acute myeloblastic leukaemia. AB - In this report we present a method for purging acute myeloid leukaemia progenitors (AML-CFU) from autologous marrow grafts. Previous studies using flow cytometry and cell sorting had indicated that the monoclonal antibody (MCA) Vim-2 reacts strongly with AML-CFU in a significant number of cases, whereas the majority of normal bone marrow precursors are Vim-2 negative. To investigate the applicability of Vim-2 for selective purging, we performed complement-dependent cytotoxicity experiments and determined the specific lysis of AML-CFU. In 11 of 17 patients, 97.5 +/- 4% (mean +/- SD) of AML-CFU were killed following immune mediated lysis. Multi-lineage normal haematopoietic progenitors (CFU-GEMM) were not significantly affected by the MCA Vim-2-mediated complement lysis. These data suggest that the MCA Vim-2 is a useful reagent for the elimination of residual AML progenitor cells from remission bone marrow in patients subjected to autologous marrow transplantation. PMID- 3332164 TI - CFU-GEMM correlate with neutrophil and platelet recovery in patients receiving autologous marrow transplantation after high-dose melphalan chemotherapy. AB - CFU-GEMM, multipotent progenitor cells, give rise to erythroid, granulocyte macrophage and megakaryocytic cells. We have examined the utility of this assay for predicting hematologic recovery in patients treated with high-dose chemotherapy and autologous marrow rescue with cryopreserved marrow. In marrow samples from 50 patients CFU-E, BFU-E and CFU-GEMM significantly decreased following cryopreservation. The median value for CFU-E declined from 132,659 to 10,648, BFU-E decreased from 36,112 to 3345 and CFU-GEMM decreased from 3242 to 260 colonies per ml of marrow frozen. Once cryopreserved, the number of CFU-E, BFU-E and CFU-GEMM remained stable with prolonged storage in liquid nitrogen. In 48 patients uniformly treated with high-dose melphalan (180 mg/m2) and rescued with cryopreserved autologous marrow, univariate analyses showed that the time to platelet recovery (greater than 50 x 10(9)/l) was correlated with the number of CFU-E, BFU-E and CFU-GEMM infused (p less than 0.05). The time to neutrophil recovery was only correlated with the number of BFU-E and CFU-GEMM infused (p less than 0.01). However, by multivariate analyses, only the number of CFU-GEMM, and not CFU-E and BFU-E, infused correlated both with the time to neutrophil and platelet recovery. These data indicate that the CFU-GEMM assay may be useful for determining the repopulating ability of cryopreserved bone marrow. PMID- 3332165 TI - Aspergillus infections in bone marrow transplant recipients. AB - Aspergillus infection was studied in patients admitted to the Bone Marrow Transplant (BMT) Service at the Johns Hopkins Oncology Center during a 9-year period. The overall incidence was 4% in 549 patients reviewed. The incidence at autopsy was 12% (21 of 174 patients autopsied). There was no difference in frequency of occurrence in allogeneic compared to autologous BMT recipients. However, all infections in autologous BMT patients (5 of 5) occurred during neutropenia before engraftment. In contrast, 16 of 17 infections in allogeneic BMT patients occurred after engraftment (p = 0.0002). This difference presumably related to differences in duration of neutropenia and immunodeficiency. Age, underlying disease, date of BMT, preparative regimen, remission status, prior treatment, interstitial pneumonitis and concomitant cytomegalovirus infection did not predispose patients to aspergillus infection. Different post-BMT immunosuppressive regimens did not affect the risk for aspergillus infection except that patients who were given cyclophosphamide plus methylprednisolone had a higher incidence of aspergillus infection than those given methotrexate (12% versus 1%, p = 0.03). Acute graft-versus-host disease imposed a slight risk for infection (p = 0.06). PMID- 3332166 TI - Acute renal failure associated with autologous bone marrow transplantation. AB - A review of 33 consecutive autologous bone marrow transplant (BMT) cases revealed three cases of acute renal failure which developed immediately following reinfusion of cryopreserved bone marrow, and which could not be explained on the basis of hypotension or nephrotoxic drugs. Gross hemoglobinuria was noted in all 33 autologous BMT patients, and may have contributed to the acute renal failure seen in the three patients. Histologic examination of the kidneys of one patient who died 3 days after BMT showed markedly dilated renal tubules filled with hemoglobin casts. The kidneys of the other two patients, who died 8 and 20 days after BMT, showed renal tubular necrosis and regeneration with numerous hemoglobin casts. All three patients had systemic candidiasis at autopsy, and there is evidence to suggest that the infection was also present at the time of BMT. Fungal sepsis may have predisposed these patients to the development of acute renal failure. We recommend the use of procedures that minimize the hemolysate content of cryopreserved bone marrow. PMID- 3332167 TI - Acute acquired demyelinating polyneuropathy with respiratory failure following high-dose systemic cytosine arabinoside and marrow transplantation. AB - Reversible ventilatory failure secondary to acute, acquired polyneuropathy developed in a patient undergoing marrow transplantation for chronic myelogenous leukemia. The onset of the neuropathy was temporally related to the conditioning regimen of high-dose, systemic cytosine arabinoside (Ara-C). The clinical features and course were consistent with the Guillain-Barre syndrome and no other conditions causally associated with the syndrome were noted. Although central nervous system toxicity is a well recognized complication of high-dose Ara-C, peripheral neuropathy is infrequently reported. Possible mechanisms of peripheral polyneuropathy in this marrow transplant recipient are discussed. PMID- 3332168 TI - T cell-depleted allogeneic bone marrow transplantation in a case of childhood idiopathic myelofibrosis. AB - An 11-year-old boy developed primary myelofibrosis. Nine months after diagnosis he received high-dose chemoradiotherapy followed by T cell-depleted allogeneic bone marrow transplantation as primary therapy. Sixteen months after grafting the patient is well, with reversal of the marrow sclerosis and no evidence of chronic graft-versus-host disease. PMID- 3332169 TI - Pericardial effusion following conditioning for bone marrow transplantation in acute leukaemia. AB - We report the details of a young woman in whom pericardial tamponade developed acutely following preparation for allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. The aetiology of the effusion, though uncertain, probably relates to the cumulative cardiotoxicity of cyclophosphamide and irradiation upon a myocardium previously sensitised by anthracycline therapy. As the number of transplant procedures increases, this complication may become more common, and might be avoided by a more critical assessment of cardiac function prior to transplantation, with radionuclide angiography. PMID- 3332170 TI - High-dose busulphan and cyclophosphamide as the primary preparative regimen for marrow transplantation in chronic myeloid leukaemia. PMID- 3332171 TI - Autologous bone marrow transplantation in acute leukaemia. AB - Intensive chemoradiotherapy with autologous bone marrow rescue has been widely explored as treatment for acute myeloblastic and acute lymphoblastic leukaemia. Encouraging preliminary results have been reported but in no situation has this modality of therapy been proved to be superior to conventional chemotherapy. Attempts to remove minimal residual disease from the harvested marrow have been made by both immunological and pharmacological means, but the value of such procedures has not been tested rigorously. Determination of the precise role of autologous bone marrow transplantation in the treatment of acute leukaemia must await the outcome of randomised controlled trials and will take several years. PMID- 3332172 TI - Marrow transplantation for malignant lymphoma. AB - With a large number of patients treated, some more than a decade ago, it is now clear that the use of high-dose therapy combined with marrow transplantation can cure some patients of malignant lymphoma who are otherwise incurable. Two major questions which are considered in this review are: (1) how can currently available transplant techniques be best applied, and (2) how do we go about developing more effective transplant regimens? PMID- 3332173 TI - Graft-versus-leukemia following bone marrow transplantation. AB - Considerable data in animals suggest an anti-leukemia reaction associated with transplantation of allogeneic bone marrow cells. In some instances, this graft versus leukemia (GVL) reaction may be distinct from graft-versus-host-disease (GVHD). Data in humans also support the concept of a GVL effect associated with bone marrow transplantation. These observations include an increased risk of leukemia relapse in identical twin transplants and in recipients of T cell depleted allogeneic transplants, and a decreased risk-of leukemia relapse in individuals who develop acute or chronic GVHD. These findings are among the most convincing evidence that the immune system plays a role against cancer in man. PMID- 3332174 TI - The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation. AB - The results are presented of allogeneic transplantation for 363 patients with acute non-lymphoblastic leukemia treated in Seattle from May 1973 through December 1985. The probabilities of surviving disease-free for 5 years for patients transplanted in first remission, in second remission, in untreated first relapse or in chemotherapy-resistant first relapse were 46%, 28%, 30%, and 21%, respectively. The corresponding probabilities of relapse within 5 years were 25%, 37%, 36% and 56%, respectively. Prognostic factors predictive of survival after marrow transplantation for patients transplanted in first remission included age, donor sex and the number of circulating blasts at the time of diagnosis. Acute graft-versus-host disease (GVHD) had a major adverse effect on survival, but chronic GVHD decreased the risk of relapse for patients transplanted in first remission. PMID- 3332175 TI - Effects of low dose rate irradiation on human marrow hematopoietic and microenvironmental cells: sparing effect upon survival of stromal and leukemic cells. AB - The effects of different dose rates of in vitro irradiation on the proliferative capacity of marrow stromal, hematopoietic and leukemic colony-forming cells (CFC) are described. Marrow cell suspensions, HL-60 cells and trypsin-dispersed fibroblasts were irradiated at 5 or 45 cGy/min and then assayed for CFC. Irradiation at low (5 cGy/min) compared to high (45 cGy/min) dose rate showed a significant difference in survival of stromal and of HL-60 cells, but not of hematopoietic progenitors: the respective D0 values were 170 and 120 (p = 0.003) for marrow fibroblastic progenitors (CFU-F); 145 and 110 (p = 0.005) for passaged marrow fibroblasts (CFU-F); 170 and 140 (p = 0.045) for HL-60 cells; 85 and 85 for multipotential CFC (CFU-mix); 125 and 120 for erythroid progenitors (BFU-E); and 115 and 120 for granulomonopoietic progenitors (CFU-GM) (p = 0.5 for hematopoietic clonogenic cells). Marrow suspensions did not establish confluent stromal layers in long-term marrow cultures following irradiation with 600 cGy at 45 cGy/min, whereas after 840 cGy at 5 cGy/min confluent stromal layers were obtained. This indicates that low dose rate-sparing effect applies to all stromal cell progenitors. Confluent stromal layers derived from progenitors surviving irradiation sustained hematopoiesis as well as controls when co-cultured with fresh hematopoietic cells. Adherent layers in long-term marrow cultures irradiated after establishment with doses less than or equal to 1500 cGy at 5 or 45 cGy/min also showed normal hematopoietic supportive function when co-cultured with freshly isolated hematopoietic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332176 TI - Poor graft function associated with graft-versus-host disease after allogeneic marrow transplantation. AB - This is a retrospective analysis of marrow function in 171 recipients of an HLA matched bone marrow transplant (BMT). Only patients with detectable hemopoiesis as indicated by leukocyte counts greater than 1.0 x 10(9)/l and platelet counts greater than 25 x 10(9)/l who were alive on day 30 were entered in the study. Poor marrow function was detected in 24 (14%) patients as indicated by a decrease in the peripheral blood counts to less than 40% of the maximal preceding values post-transplant in association with reduced marrow cellularity. Leukopenia (n = 4), thrombocytopenia (n = 3) or a combination of the two (n = 17) occurred 62 +/- 23 (SEM) days post-transplant and was associated with acute graft-versus-host disease (AGVHD) grade II or more and infection (n = 19) in the absence of clear rejection or persistence/recurrence of malignant disease. A multivariate analysis showed that AGVHD was the major risk factor (p = 0.001) for developing poor graft function. In the 24 patients with poor graft function, hemopoietic recovery was strongly associated with resolution of AGVHD and of infections. Their survival (27%) was the same as survival for other patients matched for GVHD who had no pancytopenia. The causes of death were GVHD (n = 13), pneumonia (n = 3) and infections (n = 1). This study draws attention to a particular type of poor graft function following allogeneic BMT that is characterized by (1) normal timing and quality of engraftment, (2) AGVHD of grade II or greater, (3) progressive and severe pancytopenia, and (4) multiple infections with poor clinical condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332177 TI - Legionnaires' disease after bone marrow transplantation. AB - Four patients developed legionnaires' disease after bone marrow transplantation. Two cases occurred early after transplant and were considered as part of a hospital epidemic due to contamination of water supply. The other two cases were considered to be sporadic because they occurred 3-4 weeks after hospital discharge. The outcome was good in two patients. In the third patient, recurrent disease was probably due to acquired resistance to macrolides, and complete cure was achieved after treatment with pefloxacin and rifampicin. The fourth patient died of overwhelming infection despite early treatment with erythromycin and pefloxacin. During the same period we treated 14 patients with pefloxacin for prevention of bacterial infection, of whom none developed Legionella pneumophila infection, while three of the patients reported here were in a group of 11 patients who received only oral non-absorbable antibiotics for gut decontamination. The fourth patient in this report was receiving no antibiotics. Thus pefloxacin seems to be effective as prophylaxis against L. pneumophila infection. When the hospital water supply was heated to 60 degrees C and chlorinated, the nosocomial cases in the hospital completely disappeared. PMID- 3332178 TI - Mediastinal emphysema in marrow transplant recipients. AB - Six of 146 patients at our institution developed mediastinal emphysema following marrow transplantation. Five patients were the recipients of marrow from their HLA fully matched sibling donors and one patient had an autologous marrow transplant. Features common to all included single-dose total body irradiation and high-dose systemic adrenocorticosteroids. Five of the patients had clinical and radiological evidence of recent or active interstitial pneumonitis. The clinical implications and possible aetiologies of mediastinal emphysema developing in the post-transplant patient are discussed. PMID- 3332179 TI - Invasive Trichosporon cutaneum infection: an increasing problem in immunosuppressed patients. AB - Trichosporon cutaneum (syn. T. beigelii), a saprophytic fungal organism normally found in the soil, is increasingly being recognized as a cause of life threatening systemic illness in immunosuppressed patients. Of 42 cases reported in the literature, 27 (64%) have died, including all four occurring after bone marrow transplantation. We report here a 44-year-old man who developed an invasive pulmonary infection and fungemia with T. cutaneum following bone marrow transplantation. The infection was manifest by severe respiratory distress and hypoxemia despite a clear chest X-ray, and was diagnosed by the identification of fungal hyphae on a percutaneous lung aspirate and by culture of the organism from the blood. Despite the previous reports indicating that there is a high mortality rate in this situation, the patient recovered following treatment with amphotericin B, miconazole and ketoconazole. T. cutaneum needs to be recognized as a potentially serious but treatable pathogen in severely immunosuppressed patients, including bone marrow transplant recipients. PMID- 3332180 TI - Pregnancy after bone marrow transplantation for severe aplastic anemia. AB - Two women suffering from severe aplastic anemia were treated by bone marrow transplantation (BMT). They became pregnant 17 and 40 months after the procedure. During the first 20 weeks of pregnancy, one of them continued to receive cyclosporin A (CSA) to prevent graft-versus-host disease. Her CSA serum levels during these first 4 months ranged from 35 to 280 ng/ml. The course of pregnancy was uneventful and a healthy boy was delivered at term by Cesarean section. The other patient was shown to have rejected the transplanted marrow 4 months after BMT; autologous regeneration had occurred. During the last 2 months of her pregnancy, the hemoglobin and platelet numbers decreased again. Nevertheless, a healthy girl was delivered at term. Three months after delivery this patient's hematologic parameters are almost back to normal. PMID- 3332181 TI - Cellular infiltrates in the target organs associated with acute graft-versus-host disease. AB - Acute graft-versus-host disease (AGVHD) has been one of the major obstacles in successful bone marrow transplantation for many years. The histologic manifestations of AGVHD have been well defined but much less is known about the cellular infiltrates in the target organs during AGVHD, the structure of the inflammation is different in different target organs and is not necessarily similar to classical allograft rejection. This review covers, in addition to the histologic approach, the cytologic and functional approaches to the AGVHD associated with inflammatory cells. PMID- 3332182 TI - The role of T-cells in preventing relapse in chronic myelogenous leukemia. AB - Bone marrow transplantation is effective in eradicating leukemia in over 90% of patients with chronic myelogenous leukemia (CML). This efficacy relates to some extent to the antileukemia effect of high-dose chemotherapy and radiation. An immune-mediated antileukemia effect of graft-versus-host disease is also important. In CML, a novel T-cell-mediated mechanism of leukemia eradication is also probably active. In this article we describe this novel mechanism, present preliminary data to support the notion and suggest that it might be exploited to treat CML in a context other than bone marrow transplantation. PMID- 3332183 TI - Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission. AB - Forty-six patients with acute lymphoblastic leukemia (ALL) in first marrow remission underwent allogeneic marrow transplantation between August 1976 and June 1985. Thirty-four patients had no extramedullary disease after remission induction and 12 had extramedullary relapses prior to or at the time of marrow grafting. The conditioning regimen included cyclophosphamide followed by total body irradiation, 9.2-15.75 Gy, administered as a single dose or in six or seven daily fractions. Marrow donors were genotypically HLA-identical siblings. Methotrexate was given as prophylaxis for graft-versus-host disease (GVHD). Forty four patients had marrow engraftment. The incidence of grades II-IV acute GVHD was 52%. Clinical chronic GVHD occurred in 21 patients. Eighteen patients are alive 1-9 years (median = 4.2 years) after marrow grafting, 15 of whom are in continuous complete remission. The estimated probability of relapse within 2 years (+/- standard error) is 41 +/- 9% and the probability of relapse-free survival at 5 years is 28 +/- 7%. Major causes of death were recurrent leukemia, acute GVHD and interstitial pneumonia. Actuarial probabilities of survival, relapse and disease-free survival were not significantly different between those patients who did and those who did not have extramedullary disease after attaining first marrow remission. PMID- 3332184 TI - Bone marrow transplantation for acute non-lymphocytic leukemia: a report from the Childrens Cancer Study Group of sixty-seven children transplanted in first remission. AB - Sixty-seven children with acute non-lymphocytic leukemia (ANLL) in first remission underwent HLA-identical sibling bone marrow transplants as part of a cooperative study by the Childrens Cancer Study Group. Three patients died of sepsis before marrow recovery. Sixty-four patients recovered marrow function and have been followed for a median of greater than 1300 days. Two-year actuarial survival is 59% (95% confidence interval (CI): 47-71%). The risk of relapse by 2 years is 16% (95% CI: 6-26). All relapses occurred among patients with single dose irradiation (p = 0.07), but these patients also experienced a diminished risk of acute graft-versus-host disease (AGVHD) (p = 0.12) compared to patients conditioned with fractionated irradiation. Radiation technique (single-dose vs fractionated) did not affect survival or the risk of development of interstitial pneumonia. Significant AGVHD (greater than or equal to grade II) occurred in 27 patients (40%). Patients with AGVHD were at increased risk of death due to sepsis or interstitial pneumonia during the first year after transplant, but disease free survival was unaffected by AGVHD, because all 10 relapses occurred in patients without significant AGVHD. Neither survival nor relapse risk were affected by patient age, sex, white cell count at diagnosis, or FAB classification. This collaborative transplant study has resulted in survival data comparable to those of single institutions and the best reported outcomes of conventional chemotherapy. PMID- 3332185 TI - Improved survival of dogs exposed to fission neutron irradiation and transplanted with DLA identical bone marrow. AB - The survival of dogs exposed to fission neutron irradiation, a component in the radiation dose of reactor accidents, was improved by the administration of DLA identical allogeneic bone marrow but not by the administration of DLA-mismatched allogeneic bone marrow. The level of survival observed at 2.55 Gy was similar to that observed after autologous bone marrow transplantation. The transplanted allogeneic bone marrow, however, survived for only 2-3 weeks, but provided enough mature peripheral blood cells during this time to endure the initial radiation insult. Subsequent recovery of autologous bone marrow led to the ultimate survival of the dogs. Additional radiation protocols were evaluated in order to obtain permanent engraftment of the donor marrow cells. A higher neutron dose or a second radiation of 6.0 Gy gamma rays led to severe damage of the gastrointestinal tract and an early death. A third regimen, a second radiation dose of 4.0 Gy of gamma rays, led to permanent engraftment in one dog but its survival was complicated by graft-versus-host disease. PMID- 3332186 TI - Preparative regimens for marrow transplantation containing busulphan are associated with haemorrhagic cystitis and hepatic veno-occlusive disease but a short duration of leucopenia and little oro-pharyngeal mucositis. AB - One-hundred-and-forty-three patients with haematological malignancy or severe aplastic anaemia received HLA-identical sibling bone marrow transplants. In 111 of these patients who had haematological malignancy and who were prepared for transplant with cyclophosphamide 120 mg/kg and fractionated total body irradiation 12-14 Gy, the incidence of haemorrhagic cystitis and hepatic veno occlusive disease was 13% and 3%, respectively. In contrast, the incidence in 15 leukaemic patients prepared for transplant with chemotherapy regimens containing high-dose busulphan was 47% and 20%, respectively (p less than 0.001). Two patients in this latter group who developed fatal veno-occlusive disease had chronic myeloid leukaemia and had received long-term low-dose busulphan pre transplant. Neither complication occurred in 26 patients prepared by cyclophosphamide alone (20 patients with severe aplastic anaemia) or with cyclophosphamide and melphalan (six patients with leukaemia). The regimen of busulphan 16 mg/kg in combination with cyclophosphamide 120 mg/kg was associated with a short duration of total leucopenia with a significantly higher leucocyte count on the day of marrow transplant compared to other regimens. Furthermore, oro-pharyngeal mucositis was not severe even when methotrexate was utilised as post-transplant prophylaxis for graft-versus-host disease. Thus, while the busulphan-cyclophosphamide regimen appeared useful, we suggest that (1) high-dose busulphan should not be used as a preparative regimen for patients previously exposed to busulphan, and (2) bladder irrigation (as well as intravenous hydration) is necessary to minimise haemorrhagic cystitis in patients given regimens that incorporate high-dose busulphan. PMID- 3332187 TI - The effect of T lymphocyte depletion on susceptibility to influenza virus infection and development of anti-viral immunity in lethally irradiated mice reconstituted with syngeneic bone marrow grafts. AB - Lethally irradiated Balb/c mice reconstituted with syngeneic T cell-depleted or syngeneic untreated bone marrow (BM) were able to produce equal levels of hemagglutination inhibition (HI) antibodies at 4 weeks after bone marrow transplantation (BMT) in response to nasal infection with A/PR8 influenza virus given 1 week after BMT. Likewise, no differences in mortality rates could be observed following influenza virus infection 1 day after BMT. Antibody production was detected in 10-20% of BMT recipients. All animals responded to a secondary infection given 2 months later by production of secondary IgG-type HI antibodies. Mice reconstituted with BM enriched with spleen cells obtained from immune donors showed an improved survival rate as compared with recipients of naive BM, immune BM or T-depleted BM obtained from immune mice. Our results indicate that T cell depletion by itself does not increase susceptibility of syngeneic BMT recipients to virus infection. However, immune spleen cells may play a significant role in conveying protection against influenza virus infections. Although recipients of both immune and naive intact BM may mount better anti-influenza titers as compared with T-lymphocyte-depleted BMT recipients, it appears that the proportion of immune donor T cells in the marrow inoculum is insufficient for protection against influenza virus infection. Generation of memory cells to influenza viral antigens in the post-BMT period is not impaired in recipients of T-depleted marrow grafts, suggesting that memory cell precursors are unaffected by the T cell depletion procedure, or else that they were regenerated during the immediate post-BMT period from Thy 1.2-negative precursors. PMID- 3332188 TI - Influence of single and double immunomagnetic depletion on the hemopoietic capacity of marrow in patients with advanced neuroblastoma submitted to autologous bone marrow transplantation. AB - Eighteen marrows from 16 patients with advanced neuroblastoma were submitted to a single or double immunomagnetic depletion procedure to purge them of tumor cells. Analysis of results showed that the CFU-GM recoveries were 59% +/- 16 (SE) and 33% +/- 16 after one or two cycles of incubation with microspheres. This led to yields of 7.8 x 10(4) and 4.1 x 10(4) CFU-GM available per kg body weight, respectively. Successful engraftment was demonstrated in all evaluable patients. However, some patients had delayed hematologic recoveries, particularly for platelets. PMID- 3332190 TI - Monoclonal rat anti-human lymphocyte antibody Campath-1 binds to T and B lymphocytes but effectively lyses only T cells. AB - Binding and human complement-mediated T and B lymphocyte lysis were investigated in bone marrow samples obtained from 15 normal donors and 12 patients with a variety of malignant disorders undergoing marrow cryopreservation prior to autologous bone marrow transplantation. All marrow samples were obtained during remission except for one patient with neuroblastoma. The mononuclear cell fractions were collected and the distribution of B cell restricted markers (surface Ig and GP-70) and T cell surface markers (Leu-1 and rosettes with sheep red blood cells) were studied before and after marrow purging with Campath-1, a monoclonal rat anti-human lymphocyte antibody, and autologous serum as complement. Effective lysis of T lymphocytes (greater than 99.5%) was documented in all cases. However, although effective binding of Campath-1 to B lymphocytes was uniform, no effective lysis occurred. The data suggest that effective lysis of mature T lymphocytes can be accomplished while leaving normal B lymphocytes intact. PMID- 3332189 TI - Avascular necrosis of the femoral head secondary to corticosteroid therapy for graft-versus-host disease after marrow transplantation: effective therapy with hip arthroplasty. AB - Of 50 patients surviving 2 years or longer after HLA-identical sibling bone marrow transplantation for haematological malignancy or severe aplastic anaemia, five developed avascular necrosis of the femoral head. All had previously received corticosteroid therapy post-transplant for graft-versus-host disease. Median day of onset of symptoms was 545 days post-transplant (range 249-731). Clinical, radiological and radionuclide findings were typical of osteonecrosis. One patient has had bilateral hemiarthroplasties and one total hip replacements performed, both with excellent results. Bilateral arthroplasties are planned for a third patient but, interestingly, the disease process in the other two patients has been relatively mild with no progression over a period of greater than 256 and greater than 825 days, respectively. Since one patient had as little as 14 days treatment with prednisone, this complication should be borne in mind when designing prophylactic regimens for minimisation of GVHD that include corticosteroids. PMID- 3332191 TI - Recovery of the ability to induce immune resistance against L1210 lymphatic leukemia in semisyngeneic CD2F1 mice after lethal irradiation and reconstitution with bone marrow purged of leukemia with mafosfamide (ASTA Z 7654). AB - Balb/c x DBA/2 F1 (CD2F1) mice were lethally irradiated (TBI) and reconstituted with syngeneic bone marrow cells (SBMT) untreated or treated with mafosfamide (ASTA Z 7654) for ex vivo purging of semisyngeneic L1210 leukemia (TBI + SBMT or TBI + SBMT-Maf mice, respectively). At various times after irradiation and reconstitution mice were injected intraperitoneally four times at weekly intervals with 10(6) immunogenic L1210-Maf cells (L1210 cells treated in vitro with mafosfamide for inhibition of their growth in vivo). As positive controls we immunized normal (non-irradiated) CD2F1 mice. Full resistance against L1210 leukemia (as compared to normal immunized mice) could be obtained in TBI + SBMT and TBI + SBMT-Maf mice when the immunization procedure was started from day +28 or day +56 after transplantation, respectively. Earlier immunization of TBI + SBMT mice (from day +14) or TBI + SBMT-Maf mice (from day +14 or +28) caused only partial resistance against the leukemia. PMID- 3332192 TI - Treatment of adult T cell leukemia with mega-dose cyclophosphamide and total body irradiation followed by allogeneic bone marrow transplantation. AB - A 43-year-old patient with adult T cell leukemia (ATL) was treated with mega-dose cyclophosphamide and total body irradiation (TBI) followed by bone marrow transplantation (BMT) from his HLA-identical sibling who was not a carrier of ATL virus. After BMT, ATL cells rapidly decreased and disappeared, and the engraftment of marrow was confirmed on day 20. The patient showed normal hematologic recovery. However, he died on day 205 with interstitial pneumonitis caused by cytomegalovirus infection. Neither autopsy findings nor serologic and cytologic examinations showed any evidence of ATL relapse after BMT. This pilot study suggests that mega-dose chemotherapy and TBI followed by allogeneic BMT should be considered for such treatment of ATL. PMID- 3332194 TI - Borderline personality. A review of recent research. AB - Borderline personality has been, for many years, a discredited diagnostic concept. In 1979 a review of the literature concluded that its validity status was very uncertain. The authors have reviewed research conducted since then and discuss it in terms of the Robins & Guze (1970) criteria. In spite of existing unclear issues, the balance is tipping in favour of the validity of borderline personality, as diagnosed with new research criteria. This development is taking place in the context of a growing interest in the area of personality disorders. PMID- 3332193 TI - Late onset transfusion-dependent anaemia with thrombocytopenia secondary to marrow fibrosis and hypoplasia associated with chronic graft-versus-host disease. AB - Late onset transfusion-dependent anaemia is very rare in the presence of sustained engraftment after HLA-identical sibling bone marrow transplantation. The only previously described consistent cause is pyridoxine-responsive sideroblastic anaemia. We describe here a second cause, marrow hypoplasia and fibrosis, occurring in association with extensive chronic graft-versus-host disease (GVHD). A 20-year-old Caucasian male who received cyclophosphamide and fractionated total body irradiation followed by an unmanipulated HLA-identical sibling marrow transplant from his sister for acute nonlymphoblastic leukaemia in first remission developed chronic GVHD of the skin and mouth at day 101 post transplant. At day 689 post-transplant, he developed leuco-erythroblastic anaemia with thrombocytopenia, due to patchy marrow hypoplasia and fibrosis. Between days 689 and 1987 post-transplant he received 71 units of packed red cells, requiring transfusion approximately monthly. He remains well although still on prednisone for chronic GVHD of skin and is receiving desferrioxamine 4 g five nights/week i.v. as prophylaxis for iron overload. PMID- 3332195 TI - 'The schizophrenias as nervous types' revisited. AB - In 1972 the author proposed that schizophrenia represents an aberration of central nervous processes that underlie cognitive and personality characteristics which can be observed in many healthy people. The present paper brings the evidence for that theory up to date and concludes that over the past 15 years it has received considerable empirical support. The way in which the theory confronts the question of whether or not schizophrenia is a disease is also clarified. PMID- 3332196 TI - Explaining and understanding in psychopathology. AB - Psychoanalytical methodology has been described as causal explanation or hermeneutic understanding. This methodological dichotomy has been introduced into psychopathology by Karl Jaspers. Contemporary authors' contributions in the area are discussed. Although these authors accept a role for both methods, they agree with Jaspers that psychoanalysis should be subjected to the logical limitations of hermeneutic analysis. A logical framework for the interaction of explaining with understanding is presented and discussed in relation to psychiatric research. PMID- 3332197 TI - Rudolph Hess's mental illness. PMID- 3332198 TI - Hemodynamic and metabolic changes during and following operation. AB - During anesthesia and operation, there appears to be a common state wherein oxygen consumption is inadequate to meet intraoperative metabolic requirements. Although there is insufficient information to fully explain this problem, decreased intraoperative levels of cardiac output and oxygen delivery, altered intraoperative oxygen transport at the microcirculatory and cellular levels, and altered delivery of oxidative substrate are possible contributors. Anesthesia and operation thus appear to produce a physiologic pattern similar to other shock states. Postoperative physiologic changes include increased cardiac output and increased oxygen delivery, necessary to support increased oxygen consumption. These postoperative changes may represent compensatory physiologic responses to preoperative and intraoperative oxidative and metabolic deficits. There are also significant energy needs of the healing surgical wound. These additional energy requirements for wound healing add to the degree of increase in metabolism necessary for recovery from operation. The postoperative increase in oxygen consumption appears to be essential to reverse intraoperative deficits, and has been reported to have survival value. Clinically, a major goal of postoperative therapy should thus be to support these necessary physiologic compensations. Titration of postoperative therapy should therefore not be to "normal" physiologic endpoints, but to the supernormal cardiac output and oxygen transport necessary for recovery in postoperative patients. PMID- 3332199 TI - Cardiovascular effects of anesthesia and operation. AB - Anesthesia and surgery have a wide range of effects on the cardiovascular system. Even in healthy patients having minor operations, anesthetic agents can cause significant cardiac depression and hemodynamic instability. Virtually all anesthetic agents have intrinsic myocardial depressant properties, although some may mask this with sympathetic stimulation. The vasodilatory effects of the volatile agents can result in serious hypotension when combined with this negative inotropy. In the patient with pre-existing cardiac disease, these cardiovascular anesthetic effects become much more serious. These patients will not tolerate wide swings of hemodynamic variables, and the cardiodepressant effects of anesthetics are more pronounced in them. The stress of anesthesia and surgery frequently unmasks previously undiagnosed heart disease. Surgery itself provides many insults to the cardiovascular system, and these may be additive with the effects of anesthesia. These include loss of blood and other volume shifts, release of various substances into the circulation, hypothermia, sudden changes in cardiac preload and afterload, myocardial ischemia, and effects of drugs or blood products given for surgical reasons. The signs and symptoms of these surgical stresses to the cardiovascular system are often masked by anesthesia. PMID- 3332200 TI - Mechanisms of hypoxemia and hypercapnia in the perioperative period. AB - There are numerous mechanisms of hypoxemia and hypercapnia during the perioperative period. Mechanisms of hypoxemia include oxygen delivery problems, decreased FAC-CC relationship, hypoventilation, decreased cardiac output, increased oxygen consumption, decreased hypoxic pulmonary vasoconstriction, and increased nonalveolar right-to-left shunting. Mechanisms of hypocapnia include increased carbon dioxide production, increased alveolar dead space, and increased external dead spaces. Pulmonary diseases often involve multiple mechanisms to produce hypoxemia and hypercapnia. PMID- 3332201 TI - Pulmonary physiology in the postoperative period. AB - After upper abdominal or thoracic surgery, loss of lung volume, manifested most importantly by reduced FRC, and abnormal gas exchange, manifested by postoperative reduction in PaO2, are the rule rather than the exception. These physiologic alterations in lung function occur in the absence of superimposed complications such as pneumonia and/or lobar atelectasis; the usual physiologic alterations do, in fact, predispose to pulmonary complications (approximate 20 per cent incidence) which, when present, further compromise lung function. The mechanisms of postoperative impairment in lung function are multiple, interactive, and at the present, incompletely understood. An attempt to summarize the more important causes of impaired postoperative lung function is shown in Figure 6. PMID- 3332202 TI - Pathophysiology, monitoring, outcome prediction, and therapy of shock states. AB - The time course of hemodynamic and oxygen transport patterns of survivors and nonsurvivors of high-risk critical illness patients was used to evaluate pathophysiologic mechanisms, develop outcome predictors, and propose therapeutic goals. The predictors and goals were tested prospectively and resulted in significantly reduced mortality and morbidity. PMID- 3332204 TI - Effect of anesthesia and surgery on renal function. AB - Interpretation of the effects of anesthesia and surgery on renal function should be based on careful appraisal of the methodology used. Currently, the most accurate measurement of in vivo RBF is provided by flow probes, although thermodilution techniques show promise. In addition, the many secondary factors that affect renal responses, such as intravascular volume status and positive pressure ventilation, should be taken into consideration in evaluating any study. Normal renal function appears to be regulated by a balance between opposing neurohormonal systems which control vasomotor tone, diuresis, and natriuresis. Surgical stress tips the balance in favor of renal vasoconstriction and salt and water retention, which may last for days after operation. Recent elucidation of the role of atrial natriuretic peptide enhances the concept that these changes can be prevented or modified by maintenance of normal or increased atrial volume. Anesthetic agents generally decrease GFR and urine output. Effects of RBF are variable and probably reflect overall circulatory responses rather than direct actions. All these changes are mild and usually reversed at the end of anesthesia. Positive pressure ventilation depresses renal function through its effects on the central circulation, which can be reversed by administration of fluid or inotropic agents. Controlled hypotensive anesthesia, aortic cross clamping, and cardiopulmonary bypass represent anticipated renal insults which should be carefully managed. PMID- 3332203 TI - Mediators of altered perioperative physiology. AB - Several recent papers have described the development of a new study discipline, psychoneuroimmunology. "The new science begins with the premise that neither the brain nor the immune system can be excluded from any scheme that proposes to account for the onset and course of human disease." This article addresses the concept as it pertains to the perioperative state. Two basic ideas are necessary framework for this discussion, the notion of reflex arcs and a definition of stress. PMID- 3332205 TI - Physiology and pathophysiology of the digestive organs in critical illness. AB - Prolongation of life in critical illness has led to the increasing involvement of the digestive organs by systemic hypoperfusion. The end result of profound ischemia is multiple systems organ failure. Digestive system failure, in most probability, becomes the terminal event. Understanding the physiology and pathophysiology of the digestive organs in critical illness allows for early detection and institution of prophylactic measures. Involvement of the liver, biliary tract, pancreas, stomach, and intestines is individually discussed. PMID- 3332206 TI - Immune response following surgical trauma. AB - In this brief review a description of changes in specific immune response with regard to surgical trauma is presented. The effect of anesthesia on these responses appears to be minimal. The mechanisms underlying functional abnormalities include serum inhibitory factors, suppressor monocytes, deficiency of lymphocyte-monocyte-associated fibronectin, and deficiency of IL-2 production. The factor of stress should be taken into consideration when interpreting the effect of surgery, because stress is known to influence various immune responses. The reason for various discrepancies among investigators appear to be due to technical differences, type of surgery, duration of surgery, temperature at which surgery was done (both hypothermia and hyperthermia modify the immune response), blood or plasma infusion (they appear to activate T-cells in vivo), underlying disease, and baseline immunologic status (for example, patients with malignancy with depressed preoperative immunologic status might be more or less susceptible to the effects of surgical trauma), nutritional status, drugs used, etc. Quantitative analysis should be done using monoclonal antibodies and FACS. In none of the studies published was FACS used. More detailed studies are required to understand non-T- and non-B-cell and macrophage functions in patients undergoing surgical trauma. Specific antibody responses should be studied to explain the high frequency of sepsis in the postoperative period. PMID- 3332207 TI - Excessive blood loss and its relationship to clotting system changes during and after major surgery. AB - The massively hemorrhaging patient still remains one of the major problems that can be faced by the general surgeon. This article attempts to summarize the biophysiology of this process in an intuitively understandable manner that has direct clinical applications. PMID- 3332208 TI - Postoperative multiple organ failure. AB - Cellular damage is the pathophysiologic basis for the postoperative multiple organ failure syndrome. This damage may be caused by pre- and intraoperative shock. Postoperative organ failure is manifested when cellular repair does not occur. Three factors may contribute to this progression to multiple organ failure: inadequate resuscitation, malnutrition, and sepsis. PMID- 3332209 TI - Epidemiology, physiopathology, and experimental therapeutics of acute spinal cord injury. AB - This article analyzes the epidemiological factors relating to acute spinal cord injury. It also delineates the anatomical and rheological characteristics of the spinal cord and denotes the latest concepts in autoregulation of spinal cord blood flow. The physiopathology of spinal cord injury is examined in terms of existing animal models, responses of the white and grey matter, and biochemical and biomechanical correlates. Experimental and clinical therapeutic modalities ranging from hypothermia to opioid antagonists, and adrenergic blockers to free radical scavengers are evaluated. PMID- 3332210 TI - Biomechanics of spinal cord injury. AB - This article summarizes the biomechanical relationship of the spinal column to load stresses with respect to column failure, and the resulting associated central nervous system injury. In addition, it presents pertinent animal research, which has focused onto the development standardized animal spinal cord injury model. PMID- 3332211 TI - Spinal cord injury--a systems approach: prevention, emergency medical services, and emergency room management. AB - Spinal cord injury is considered a catastrophic disease because of the significant morbidity, mortality, and costs not only in fiscal terms but in social terms. There are approximately ten thousand new spinal cord injuries per year with the national prevalence estimated at between three and five hundred thousand Americans. These authors advocate a systems approach for the comprehensive management of these devastating injuries. In all phases of care for the spinal-cord-injured person, the key is a team approach and a commitment to an optimal patient care program that can result in minimizing patient morbidity, mortality, and the cost of care as well as making neurologic function maximal. PMID- 3332212 TI - Radiology of acute spinal trauma. AB - Radiologic diagnostic modalities utilized to evaluate acute spine trauma include plain films, tomography, computerized tomography (CT), myelography and CT myelography, and magnetic resonance imaging. The initial evaluation is aimed at delineating the nature and extent of both boney and soft tissue injuries, with particular attention directed toward differentiating intrinsic cord damage from extrinsic spinal cord or nerve root compression that may respond to surgical intervention. The selection of the optimal radiologic diagnostic algorithm requires familiarization with the techniques and limitations of each diagnostic procedure. PMID- 3332213 TI - Electrophysiological evaluation of the patient with acute spinal cord injury. AB - This article reviews basic principles, equipment and techniques, and clinical applications of electrophysiologic monitoring in patients with spinal cord injuries. Four groups of electrophysiologic measurements are considered: Somatosensory evoked potentials (SEPs); motor evoked potentials (MEPs); electromyography (EMG) and nerve conduction studies; and late responses, including H reflex, M response, and F wave. Reports of SEP recordings in spinal cord injury, as drawn from the literature, are tabulated in detail. PMID- 3332214 TI - Critical care management of the patient with acute spinal cord injury. AB - The critical care management of acute injury to the cervical spinal cord is discussed from the perspective of the pathophysiology of the injury process and its ramifications. Emphasis is placed upon resolution of cardiovascular derangements, spinal cord resuscitation, and respiratory support utilizing practical therapeutic interventions. PMID- 3332215 TI - Stabilization procedures in the patient with acute spinal cord injury. AB - In summary, when confronted with the spinal-cord-injured patient, the surgeon must do an initial evaluation with a complete history and physical examination, order the appropriate radiographic studies, determine the stability of the spinal column, and initiate treatment with stabilization techniques. An overview of surgical stabilization procedures used for the treatment of acute spinal cord injuries has been presented. The concept of spinal stability and the determination of the location of spinal cord compression are used to determine which surgical technique should be used. With appropriate decompression and/or stabilization procedures or both, spinal-cord-injured patients may regain additional function and begin an early rehabilitation program. PMID- 3332216 TI - Urological management in the patient with acute spinal cord injury. AB - Understanding the neurophysiology of micturition has led to pharmacologic manipulation and improvement in rates of mortality and morbidity. Use of intermittent self-catheterization and the artificial urinary sphincter (AUS) has improved the "quality of life" of these patients. Implantation of various penile prostheses has improved sexual rehabilitation. Urinary diversion is the "last resort" surgery. PMID- 3332217 TI - Anesthetic considerations in the patient with acute spinal cord injury. AB - The extent and level of the spinal cord injury as well as the presence of associated injuries affects the choice of anesthetic agents, techniques, and monitoring modalities. The role of the anesthesiologist is not limited only to the administration of anesthesia, but frequently his active participation in the team approach care of the spinal cord injury patient is needed during preoperative treatment and postoperatively in the ICU setting. Understanding of the pathophysiologic changes related to the spinal cord injury helps in the delivery of better anesthetic care for severely handicapped patients. PMID- 3332218 TI - Classification of acute spinal cord injury, neurological evaluation, and neurosurgical considerations. AB - This article provides an overview of the classification of acute spinal cord injuries as well as the description of the pathophysiology and neuroanatomy of the most commonly traumatized areas of the spinal cord. The essentials of the neurological examination relative to spinal cord injuries is discussed and the specific abnormalities found in patients with spinal cord syndromes. Management principles are briefly summarized. PMID- 3332219 TI - Nursing consideration in acute spinal cord injury. AB - The nurse who cares for the SCI patient during the acute phase provides the assessment, implementation of routine care, and critical interventions necessary for survival. Although this group of patients requires the coordinated efforts of a multidisciplinary team for rehabilitation, it is the ICU nurse during the acute phase of care who lays the groundwork necessary for the patient to attain an optimal level of function. Care of the acutely ill SCI patient is a challenge that constantly demands innovative, individualized professional nursing care. PMID- 3332220 TI - Acute metabolic acid-base disorders. AB - Metabolic acid-base disturbances commonly and predictably complicate the course of many intensive care unit patients and plague the intensivists, surgeons, and anesthesiologists beset with the task of caring for them. In this article, we offer a systematic approach to the patient with the metabolic acid-base disorders that are likely to be encountered in the setting of the intensive care unit. The discussions are in no way presented as through treatments of all metabolic disorders, but rather focus on the more practical aspects, namely, clinical scenarios, diagnostic clues, and therapeutic goals. Additionally, we interject a discussion of some of the more controversial topics with regard to the therapy of metabolic disorders. PMID- 3332221 TI - Lactate metabolism. AB - Lactate is the end product of the anaerobic metabolism of glucose, and its accumulation in the blood signals an increase in production or a decrease in utilization, or both. The most common etiology of lactic acidosis is hypoperfusion, which represents an imbalance between systemic oxygen demand and oxygen availability with resultant tissue hypoxia. A wide variety of other etiologies of hyperlactatemia have been identified or implicated. However, most of these are uncommon causes, and many actually represent an associated perfusion failure. Clinical recognition of hyperlactatemia is facilitated by an awareness of the clinical settings in which it is likely to occur. Serum electrolyte and arterial blood gas studies are helpful to recognize lactic acidosis, but direct assay of blood lactate is necessary to identify milder degrees of lactate elevation, to confirm and quantitate the severity of more severe degrees, and to monitor the progress of therapy. Therapy should be directed toward measures to ensure adequate systemic oxygen delivery and specific treatment of the underlying causes. PMID- 3332222 TI - Effects of acid base disturbance, septic shock, and calcium and phosphorous abnormalities on cardiovascular function. AB - Systemic acidosis has a negative inotropic effect on myocardial function, which in the intact animal, is counteracted by the activation of the sympathoadrenal system. Although there are extensive animal data in this field, human studies quantifying the influence of systemic acidosis on myocardial function in various disease states is lacking. In patients with hypocalcemia, a single infusion of calcium does not sustain increased calcium levels, and the hemodynamic improvement is only transient. Hemodynamic changes in septic shock are complex, and there are convincing data documenting myocardial dysfunction in sepsis. There is a need for elucidating the biochemical characteristics of the myocardial depressant factor (or factors). PMID- 3332223 TI - Disordered water metabolism: hyponatremia. AB - Normal osmoregulation is maintained by the proper function and interplay of factors influencing thirst, renal water metabolism, and vasopressin secretion. In pathophysiologic states, body water homeostasis is disrupted and hyponatremia ensures. Hyponatremia associated with cardiac failure, hepatic failure, respiratory failure, diabetes mellitus, the postoperative state, and other disorders is commonly found in the critical care setting. The pathophysiology, diagnosis, and treatment of hyponatremia are discussed. PMID- 3332224 TI - Disordered sodium metabolism: sodium retention states. AB - Sodium retention frequently occurs in the critically ill patient. Sodium retention states include cardiac failure, liver failure, nephrotic syndrome, and hypoalbuminemic states. A clear understanding of the pathophysiology and the mechanism of sodium retention are essential for the proper care of these patients. PMID- 3332225 TI - Clinical approach to the hyperosmolar patient. AB - The successful evaluation and treatment of the hypertonic patient depends on a clear understanding of the differences between effective and noneffective solute and the consequences of changes in these solutes for water distribution. Measured osmolality, calculated osmolality, tonicity, and sodium concentration must be evaluated in the approach to these patients. PMID- 3332226 TI - Disorders of potassium homeostasis in critically ill patients. AB - Disorders of potassium homeostasis can be life-threatening. This is especially true in critically-ill patients, in whom concurrent disorders may exacerbate the adverse effects of both hyper- and hypokalemia. Alterations in potassium balance are usually multifunctional in origin. Four broad categories encompass the most common diseases and syndromes seen in the intensive care setting: pharmacologic agents, acid-base disturbances, hypomagnesemia, and renal insufficiency. The various influences that disturb the serum potassium concentration may either potentiate or counter-balance one another. The most important clinical manifestations of disorders of potassium homeostasis are those involving the heart: both hyper- and hypokalemia can be associated with lethal arrhythmias. Neuromuscular, renal and metabolic effects are also seen. Severe hyper- and hypokalemia, irrespective of cause, should be treated as medical emergencies. PMID- 3332227 TI - Catecholamines in critical care. AB - Catecholamines (norepinephrine, epinephrine, and dopamine) are released into circulation in response to stress and injury and as part of the body's attempt at vasoregulation in response to circulatory failure. Norepinephrine is released from sympathetic nerve terminal, and epinephrine and dopamine are released from the adrenal medulla. Plasma levels of these catecholamines have been reported to be elevated in various clinical settings: congestive heart failure, myocardial infarction, cardiopulmonary bypass, diabetic ketoacidosis, hypoxia, hemorrhage, and septic shock. These amines have both beneficial and detrimental effects on survival. Both norepinephrine and dopamine are often employed in the critically ill to selectively increase cardiocerebral and renal blood flow, respectively. PMID- 3332228 TI - Toxic nephropathies. AB - The general topic of kidney damage produced by drugs and toxins is introduced, emphasizing its clinical importance in critically ill patients. Specific toxins are then examined in detail with respect to the mechanisms of toxicity, clinical features, and management. PMID- 3332229 TI - Acute renal failure. AB - Acute renal failure is divided into its classic parts: prerenal azotemia, postrenal azotemia (obstruction), and renal azotemia (including acute tubular necrosis). The division of acute tubular necrosis into the ischemic and toxic varieties is supplemented by an analysis of toxic varieties into those caused by antibiotics, radiologic contrast agents, chemotherapeutic-immunosuppressive agents, heavy metals, organic solvents, etc. Acute tubular necrosis caused by hemoglobin and myoglobin is described in detail. The importance of urinalysis and the urinary indices in distinguishing prerenal azotemia from acute tubular necrosis is stressed. Finally, current prognosis and treatment are reviewed. PMID- 3332230 TI - Hypocalcemia and hypophosphatemia in acutely ill patients. AB - Hypocalcemia and hypophosphatemia have recently been recognized as common metabolic complications in acutely ill patients. The diagnostic and therapeutic approaches to these abnormalities are described in this article. PMID- 3332231 TI - [Ultrasonography of muscle atrophy with fatty degeneration--a case report]. PMID- 3332232 TI - Depletion of human T cells from bone marrow by monoclonal antibodies and complement. PMID- 3332233 TI - [Clinical observation of acute cervical lymphadenitis in children]. PMID- 3332234 TI - [Twenty patients with hematologic malignancies treated by allogeneic bone marrow transplantation]. PMID- 3332235 TI - [CT-guided stereotaxis in the management of brain abscesses]. PMID- 3332236 TI - The antilipemic effectiveness of aluminium clofibrate on hyperlipidemic patients with or without diabetes mellitus. PMID- 3332237 TI - Sonographic measurement of cerebral lateral ventricles in fetuses. PMID- 3332238 TI - [A study of etiology and imaging diagnosis in chronic pancreatitis]. PMID- 3332240 TI - [Spatial orientation of attention: results and theories]. PMID- 3332239 TI - Daniel Berlyne memorial lecture. Developmental psychobiology and behaviour theory: reciprocating influences. PMID- 3332241 TI - Cognitive aging: an historical introduction. PMID- 3332242 TI - Environment and the aging brain. PMID- 3332243 TI - Relaxation techniques. A self-learning module for nurses: Unit I. PMID- 3332244 TI - Coping with chronic disease, dying and death--a contribution to competence in old age. AB - This article reports empirical studies investigating coping with chronic disease, dying and death in the later years. The coping process is seen as a characteristic of "competence" in old age, as the investigations demonstrate that old people are very often able to adjust to crises and restrictions caused by disease, and at the same time maintain a stable perspective. The studies show that coping with chronic disease, dying and death are highly influenced by biography, by subjective evaluation of the past, present and future, and by access to a supportive intra- and extrafamilial network. This article discusses central concepts, such as "competence", "cognitive representation", "future perspective" and "coping", followed by a summary of empirical studies conducted by the author and investigates different groups of patients. PMID- 3332245 TI - Ageing in the hypothalamo-neurohypophysial-renal system. AB - Ageing is characterised by a failure in the maintenance of the internal environment (homeostasis) which is regulated by the hypothalamic neuroendocrine system. Of the many systems that undergo age-related degeneration is the control of water metabolism which leads to a variety of complications in the elderly. The magnocellular neurons of the hypothalamus produce the peptide anti-diuretic hormone (vasopressin) which acts on the kidney regulating water loss in the urine. This physiological axis lends itself to both fundamental studies of the cellular and molecular biology of ageing, and to studies of age-related alterations in the functional ability of elderly people. This review summarises some of the recent research into age-related changes in this system. The morphological and functional changes in the hypothalamus, neurohypophysis and kidney are described for the various species examined and the results discussed in terms of ageing in humans. PMID- 3332246 TI - Medical care in the last year of life: a review of economic and ethical issues. AB - This review article evaluates available data bearing on economic and ethical aspects of medical care in the last year of life. It analyzes limitations in the current literature and identifies areas where more research is needed. Available evidence indicates that medical expenditures in the last year of life are high. However, until studies are undertaken--analyzing the type of care dying patients receive and the appropriateness of care--one cannot conclude that the high cost of dying is due to overutilization of medical resources. Indeed, there is only a limited understanding of the factors influencing physicians' decisions to forgo or maintain life-sustaining treatments when caring for dying patients. Ethical questions posed by these decisions are identified. More comprehensive studies of these decisions - conducted in clinical practice settings and incorporating the nature and influences of patient and family preferences - are needed. Such studies would expand the current knowledge base and clarify the resolution of complex ethical dilemmas inherent in caring for dying patients. PMID- 3332248 TI - Hypertension and drug choice in the developing world. PMID- 3332247 TI - Aneurysmal bone cyst of the jaws: histological report of four cases and review of the literature. PMID- 3332249 TI - Coincident chromosomal disomy in meiotic dyads from triploid yeast. AB - Among meiotic asci produced by triploid (3N) Saccharomyces cerevisiae are cases in which exactly two of the four ascospores proliferate into colonies. Given the unique asymmetry problems inherent in distributing three chromosome homologues in meiosis, these ascospore dyads are of special interest. We have tested 40 of these dyads (80 ascospores) for their chromosome content by ascertaining whether they have inherited one or two copies of each of the sixteen yeast chromosomes from the parental triploid. Overall, then, ascospores in these dyads can be either haploid (N) or disomic (N + 1) for each chromosome. The principal results of this analysis include: (1) Coincident disomy (inheritance of two copies of a given chromosome in both members of an ascospore dyad) was detected for 15 of the 16 yeast chromosomes, and at least once in every dyad. (2) Coincident disomy increased as a function of the mean number of disomic chromosomes per spore in each dyad, but this increase differed functionally from that expected if coincident disomy in the two ascospores were a simple, meiotically independent, concomitant of multiple disomy. We conclude from these results that: (1) The ascospore dyads, as the two proliferating spores of single meioses from the triploid, represent meiotic sisters. That is, they stem from the same half of the first meiotic division. (2) Multiply-disomic meiotic segregants of yeast triploids proliferate at the expense of their multiple disomy, as cells in spore colonies experience repeated and independent disomic chromosome losses (N + 1--- N).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332250 TI - ARS activity along the yeast mitochondrial apocytochrome b region: correlation with the location of petite genomes and consensus sequences. AB - Seven MboI fragments spanning the mitochondrial apocytochrome b gene in Saccharomyces cerevisiae strain D273-10B were cloned in the BamHI site of the integrative yeast vector YIp5 and the capacity for autonomous replication was subsequently assayed in yeast. The positive correlation found between the ars like activity in four fragments and the presence of regions common to multiple ethidium bromide-induced petite (rho-) genomes suggests that the mitochondrial sequences possibly active as origins of replication in low-complexity neutral or weakly suppressive rho- mutants could be functionally related to the yeast nuclear replicator 11 nucleotide motif defined by Broach et al. (1983). PMID- 3332252 TI - [Possibilities of digital subtraction angiography in the diagnosis of tumors of the locomotor system]. PMID- 3332251 TI - DNA sequence and functional analysis of an ARS-element from the zygomycete Absidia glauca. AB - A DNA fragment of mitochondrial origin from the mucoraceous fungus Absidia glauca promoting autonomous plasmid replication in Saccharomyces cerevisiae was sequenced and functionally characterised. We could show that the original mitochondrial insert cloned in Yip5 contains two regions with ARS activity which mutually inhibit each other. All plasmid derivatives replicating in yeast are rapidly lost during growth under non-selective conditions. In addition to one ARS consensus sequence with only one base substitution, the mitochondrial insert contains 18 related sequences with two base pair exchanges. With one exception all consensus sequences are preceded by sequence motifs strongly resembling ARS boxes. PMID- 3332253 TI - Influence of the major histocompatibility complex (MHC) on the response to and expression of H-Y in rats. AB - The influence of the major histocompatibility complex (MHC) on the survival of H Y-incompatible skin grafts in rats has been determined by challenging normal and previously sensitized females of various isogenic and congenic strains with male trunk or ear skin isografts. The MHC's influence on the potency of H-Y has also been evaluated by determining the survival of male parental strain ear skin grafts on sensitized (with F1 hybrid male cells) F1 hybrid females of two different MHC congenic strains. The results indicate that, as in mice, the MHC has a dual affect on H-Y; it is involved in determining the ability of females to respond to the antigen as well as influencing its potency. PMID- 3332254 TI - Trisomy 22: report of a patient diagnosed as a neonate. AB - The present case report describes the occurrence of Trisomy 22 in a neonate. This chromosomal disorder has rarely been diagnosed in the neonatal period. A review of the literature is presented to elucidate the fact that only further diagnosis of new cases of Trisomy 22 in neonates will allow a clearer delineation of this chromosomal abnormality in the neonatal period. PMID- 3332255 TI - The cystic fibrosis locus: a progress report. PMID- 3332256 TI - Immunodeficiency disease genes on the X chromosome. PMID- 3332257 TI - Genetic markers for assessment of retinoblastoma predisposition. AB - Here we provide a conceptual framework for the application of current approaches in the analysis of retinoblastoma to the clinical setting. The aim of genetic medicine is to minimize the burden of inherited disease through appropriate diagnosis and management of patients and to maximize information, so that families can make reasonable decisions about reproduction. Recent genetic, cytogenetic and molecular genetic approaches have improved our understanding of the biological events leading to the occurrence of retinoblastoma and, in addition, have provided tools for the enhanced assessment of risk for some individuals. The knowledge, however, is incomplete and the tools imperfect, as indicated by our continued provision of risk probabilities that are neither one nor zero. We therefore hope to emphasize both the scope and the limitations of these techniques so that their application can be effectively considered. PMID- 3332258 TI - Retroviruses and the study of cell lineage. PMID- 3332259 TI - Distribution of laminin and collagens during avian neural crest development. AB - The distribution of type I, III and IV collagens and laminin during neural crest development was studied by immunofluorescence labelling of early avian embryos. These components, except type III collagen, were present prior to both cephalic and trunk neural crest appearance. Type I collagen was widely distributed throughout the embryo in the basement membranes of epithelia as well as in the extracellular spaces associated with mesenchymes. Type IV collagen and laminin shared a common distribution primarily in the basal surfaces of epithelia and in close association with developing nerves and muscle. In striking contrast with the other collagens and laminin, type III collagen appeared secondarily during embryogenesis in a restricted pattern in connective tissues. The distribution and fate of laminin and type I and IV collagens could be correlated spatially and temporally with morphogenetic events during neural crest development. Type IV collagen and lamin disappeared from the basal surface of the neural tube at sites where neural crest cells were emerging. During the course of neural crest cell migration, type I collagen was particularly abundant along migratory pathways whereas type IV collagen and laminin were distributed in the basal surfaces of the epithelia lining these pathways but were rarely seen in large amounts among neural crest cells. In contrast, termination of neural crest cell migration and aggregation into ganglia were correlated in many cases with the loss of type I collagen and with the appearance of type IV collagen and laminin among the neural crest population. Type III collagen was not observed associated with neural crest cells during their development. These observations suggest that laminin and both type I and IV collagens may be involved with different functional specificities during neural crest ontogeny. (i) Type I collagen associated with fibronectins is a major component of the extracellular spaces of the young embryo. Together with other components, it may contribute to the three-dimensional organization and functions of the matrix during neural crest cell migration. (ii) Type III collagen is apparently not required for tissue remodelling and cell migration during early embryogenesis. (iii) Type IV collagen and laminin are important components of the basal surface of epithelia and their distribution is consistent with tissue remodelling that occurs during neural crest cell emigration and aggregation into ganglia. PMID- 3332261 TI - Response of Plasmodium falciparum to chloroquine in hospital patients at Muheza, Tanzania. PMID- 3332260 TI - Basal lamina is not a barrier to neural crest cell emigration: documentation by TEM and by immunofluorescent and immunogold labelling. AB - One of the factors proposed to control initiation of migration of neural crest (NC) cells is disruption of the basal lamina (BL) that is presumed to exist over the dorsal portion of the neural tube. Previously, we discovered that, in the mouse embryo, a continuous BL is not deposited over the dorsal portion of the neural tube until emigration of the NC cells is terminated. Here, we show that the pattern of BL deposition in chick embryos is similar, but not identical, to that in the mouse. In particular, (i) patches of BL are deposited on the premigratory NC cells in the chick but not in the mouse and (ii) BL is thicker and more interstitial matrix is deposited at the same stage of development in the chick. In addition, immunofluorescent and immunogold labelling of collagen IV, laminin and fibronectin show that (i) patches of young BL contain all three molecules; (ii) collagen IV and laminin are present in BL throughout neurulation but fibronectin either disappears or becomes masked in more mature BL and (iii) collagen IV and especially fibronectin are present in the interstitial matrix, but the relative abundance of fibronectin changes with time. The simultaneous use of immunolabelling for both light and TEM sections has allowed us to determine unambiguously that presence of a basement membrane (light microscopy) does not necessarily imply presence of basal lamina. We conclude that, as in mouse, the BL cannot be involved in the timing of the initiation of migration of NC cells. Our evidence in both the mouse and the chick, together with work in the axolotl, suggests that the basic pattern of BL deposition during neurulation may be a general phenomenon in embryonic development. Moreover, these results, in conjunction with the work of others, suggest that the critical step for initiation of migration of NC cells may be the loss of adhesions between cells. PMID- 3332262 TI - Moderate potassium supplementation: ineffective in black normotensives. PMID- 3332264 TI - The assessment of primary varicose veins by Doppler ultrasound--the role of sapheno-popliteal incompetence and the short saphenous systems in calf varicosities. AB - One hundred consecutive limbs presenting with primary varicose veins to a surgical outpatient clinic were assessed clinically and by Doppler ultrasound. By this means the incidence of sapheno-femoral and sapheno-popliteal incompetence was established and the relative role of these two systems in the development of varicosities determined. PMID- 3332263 TI - The treatment of venous thrombosis of the upper and lower limbs with "APSAC" (p anisoylated streptokinase-plasminogen complex). AB - APSAC, administered by bolus injection, has been used to treat 28 patients: 14 with ilio-femoral venous thrombosis, 6 with "spontaneous" axillary-subclavian thrombosis and eight with superior vena-caval thrombosis associated with parenteral nutrition catheter. Four of the patients with lower limb deep vein thrombosis (DVT) showed partial lysis whereas the remaining 10 showed no change. Of the patients with upper limb and/or superior caval DVT seven showed complete lysis three showed partial lysis and four showed no benefit. APSAC is an effective treatment of venous thrombosis of the upper limbs. PMID- 3332265 TI - Vascular problems at the Battle of Waterloo. PMID- 3332266 TI - Observer variability with conventional and digital subtraction carotid angiograms. AB - A study was carried out to evaluate the intra- and inter-observer variability in the determination of the severity of carotid artery stenosis on conventional and digital subtraction angiograms. The primary goal was to compare the two types of contrast studies as "gold standards" for the evaluation of non-invasive tests. Linear regression analysis of the continuous variable of percentage stenosis yielded correlation coefficients from 0.90 to 0.99. Findings were also evaluated in terms of the discrete variables formed by dividing the lesions into five categories of stenosis: kappa analysis ranged from 0.53 to 0.91. Although the digital subtraction arteriograms had greater variability than conventional ones, careful measurement of the digital images can provide a reliable estimate of the degree of stenosis. PMID- 3332267 TI - Carotid endarterectomy as stroke prophylaxis. PMID- 3332268 TI - Duplex ultrasound monitoring of arterial grafts: prospective evaluation in conjunction with ankle pressure indices after femorodistal bypass. AB - Duplex scanning and ankle brachial pressure indices have been used to objectively assess 94 femoro-distal bypass grafts 4-8 weeks postoperatively. Twenty grafts were occluded. Of the 74 patent grafts, three distinct groups could be identified on the basis of the non-invasive examination. Group 1. Patent grafts with no evidence of haemodynamically significant disease. Group 2. Patent grafts with localised disease. Group 3. Patent: haemodynamically failed grafts. Ankle brachial pressure indices alone could not differentiate between occluded grafts and grafts that were patent: haemodynamically failed (group 3), or adequately separate between grafts in groups 1 and 2. Duplex scanning when combined with pressure indices identified patent grafts "at risk" due to the presence of haemodynamically significant disease. Life table analysis demonstrated appreciable differences in event free survival between group 1 grafts and "at risk" grafts (groups 2 and 3). Duplex scanning is ideal for regular postoperative surveillance and complements the use of ankle brachial pressure indices in the follow-up of femoro-distal grafts. PMID- 3332269 TI - Duplex ultrasound assessment of femorodistal grafts: correlation with angiography. AB - Fifty-eight grafts have been assessed using duplex scanning and ankle brachial pressure indices. This assessment is compared with the findings by angiography. Eighteen grafts were occluded and 40 patent. Duplex scanning defined graft status with a greater accuracy than pressure indices. Pressure indices alone would not differentiate "satisfactory" grafts from those with localised, haemodynamically significant disease. Only 55% of those grafts with localised stenoses demonstrated a fall of greater than 0.2 in ankle brachial pressure index after exercise. When the information obtained using pressure indices and duplex scanning was combined non-invasive assessment had a sensitivity of 86% and specificity of 94% for detection of localised, haemodynamically significant disease in patent grafts. Haemodynamically significant disease, as defined by angiography, can be detected and localised with duplex scanning complementing the use of pressure indices in graft assessment. PMID- 3332270 TI - Tracheal compression by an innominate artery aneurysm. PMID- 3332271 TI - A new method using medical ultrasound for measuring femoral anteversion (torsion): technique and reliability. An intra-observer and inter-observer study on dried bones from human adults. AB - The purpose of this study was to evaluate an ultrasound method on dried femora to decide if it is sufficiently reliable to consider its application to living subjects in health and disease. It reports the application of a standard static image B-mode ultrasound scanner to measure femoral anteversion (strictly torsion) on dried bones. The method involves creating images of bony surface contours at both the upper and the lower ends of the femur placed in a water bath. The calculation of femoral torsion involves measuring the angular difference between a head-neck line at the upper end and a transcondylar line at the lower end of the femur. This approach, using the surface contour of the bone at the upper end of the femur, is similar to that used by Lange & Pitzen (1921) and differs from conventional ways of measuring anteversion in dried bones using a central femoral head-neck axis. It is shown that in ultrasound scanning of the upper end of the dried femur to measure femoral anteversion, the head-neck line must be at, or rostral to, the base of greater trochanter. The intra- and inter-observer reliability was assessed in 10 femora, each scanned ten times by two observers. It is shown that femoral torsion can be measured by the ultrasound method to an accuracy of +/- 2 degrees (95% confidence limits) without a significant difference between the observers. The ultrasound method is compared with a new mechanical method for creating surface contours at both ends of the femur and found not to be statistically different in 37 femora. Two real-time ultrasound methods reported by other workers for measuring femoral anteversion in dried bones are reviewed. It is suggested that in applying ultrasound to measure femoral anteversion in living subjects, the B-mode static image scanner is superior to the use of real-time scanners. PMID- 3332273 TI - A stereotaxic atlas of the medulla oblongata of the goat's brain. AB - A stereotaxic atlas has been prepared for the medulla oblongata of the adult goat's brain using the technique described previously (Tindal et al. 1968). The atlas consists of transverse stereotaxic planes passing caudally at 1 mm intervals from posterior 10 mm (P10) at the level of the junction between brainstem and cerebellum to posterior 20 mm (P20) at the level of the obex. PMID- 3332274 TI - In memoriam. R. D. Lockhart. PMID- 3332272 TI - Collagen organisation in the interspinous ligament and its relationship to tissue function. AB - X-ray diffraction and determination of optical anisotropy show that collagen fibres in pig and human lumbar interspinous ligaments tend to be orientated parallel to the spinous processes. There is a distribution of fibre orientations about this preferred direction. Flexion of the spine does not change the direction of preferred orientation but the angular spread of fibres increases. This pattern of collagen fibre orientations is consistent with the interspinous ligaments being able to transmit tension from the thoracolumbar fascia to the vertebrae. Since the collagen fibres tend to be aligned antero-posteriorly, they provide a high efficiency of reinforcement in this direction. The lack of fibres orientated perpendicular to the spinous processes will lead to low strength in the cranio-caudal direction so that the ligament can provide little resistance to flexion of the spine. PMID- 3332275 TI - Granule swelling and membrane fusion in exocytosis. PMID- 3332276 TI - Hydrostatic pressure in epidermal cells is dependent on Ca-mediated contractions. AB - Volume/osmotic pressure relationships were compared in Xenopus epidermal cells treated with the calcium antagonist lanthanum and in control cells. In lanthanum treated cells the volume was found to be proportional to the reciprocal of the osmotic pressure in the hypotonic range, but not in the control cells. This difference is interpreted as being caused by contractions of the actomyosin system in control cells, which require external calcium. On the basis of the different slopes of the measurements under these two conditions the contractile force of the cells in isotonic conditions was calculated to be 0.96 x 10(5)Nm-2. The observation that in hypotonic media the cell body is enlarged in the direction of movement provides evidence that the cell body/lamella transition region is the part of the cell that contracts most during locomotion. By analysing cell speed in media with varying osmotic pressures, the relationship between internal pressure and cell locomotion was revealed. PMID- 3332277 TI - Vimentin intermediate filaments in fish melanophores. AB - The distribution and chemical composition of intermediate filaments in cultured melanophores of two teleost species - Gymnocorymbus ternetzi and Pterophyllum scalare - were studied by immunofluorescence staining and immunoblotting techniques. The immunofluorescence staining of the melanophores with monoclonal and polyclonal antibodies to the intermediate filament protein vimentin revealed a system of fibrils radiating from the cell centre. These fibrils were resistant to 0.6 M-KCl and nocodazole treatments as has been found in other cell types. Transmission electron microscopy confirmed the presence of intermediate filaments in melanophores. Immunoblotting experiments showed the presence of the intermediate filament protein vimentin in melanophore lysates. Therefore, teleost melanophores possess a developed radial system of vimentin intermediate filaments. PMID- 3332278 TI - Long-latency somatosensory evoked potentials. AB - Theoretically, long-latency somatosensory evoked potentials (SEPs) provide information on the function of somatosensory associative cortical structures. Their potential role in clinical studies and research has been hampered by the lack of standardized methodology in the use of these SEPs. Other factors, such as drugs, simultaneous stimuli, and state of consciousness, also have far-reaching influences on the various parameters of long-latency SEPs. The knowledge of the origin of most SEP components is at best fragmentary; studies on clinical electrophysiological correlations seem to be hopeful in this respect. As yet, clinical applications of long-latency SEPs are limited; for future research, studies of disturbances of SEPs are most promising, mainly with regard to diseases of the gray matter, the influence of drugs on the cerebral function, and psychopathology. PMID- 3332279 TI - Quantitative analysis of individual motor unit potentials: a proposition for standardized terminology and criteria for measurement. AB - The physiology of the motor unit potential (MUP) is reviewed. The aim is to identify the electrophysiological events in the motor unit that generate the individual parts of the MUP. This is based on insight gained from new experimental techniques, such as single-fiber electromyography (EMG), scanning EMG, and simulation studies of the MUP. A terminology for the different parts of the MUP is also suggested, and nine parameters used to describe different features of the MUP are delineated: duration, spike duration, amplitude, area, spike area, phases, turns, satellites, and variability. Technical aspects, such as electrode type, filtering, and sampling rate of the computers, are discussed as well. In Appendix A, different manual and computer-aided methods for quantitative MUP analysis are described. Despite minor systematic differences between the methods, MUP durations measured by different methods correlate highly with each other (Appendix B). The manual and computer-aided methods have comparable variability between repeated measurements. PMID- 3332280 TI - Consensus: pain management ineffective. PMID- 3332281 TI - The clinical nurse researcher: new perspectives. PMID- 3332282 TI - The emergence of clinical scholarship as a professional imperative. PMID- 3332283 TI - Current topics and concepts of lactate and gas exchange thresholds. PMID- 3332284 TI - Topical ocular drug delivery: recent developments and future challenges. AB - Existing ocular drug delivery systems are fairly primitive and inefficient, but the stage is set for the rational design of newer and significantly improved systems. The focus of this review is on recent developments in topical ocular drug delivery systems relative to their success in overcoming the constraints imposed by the eye and to the improvements that have yet to be made. In addition, this review attempts to place in perspective the importance of pharmacokinetic modeling, ocular drug pharmacokinetic and bioavailability studies, and choice of animal models in the design and evaluation of these delivery systems. Five future challenges are perceived to confront the field. These are: (a) The extent to which the protective mechanisms of the eye can be safely altered to facilitate drug absorption, (b) Delivery of drugs to the posterior portion of the eye from topical dosing, (c) Topical delivery of macromolecular drugs including those derived from biotechnology, (d) Improved technology which will permit non invasive monitoring of ocular drug movement, and (e) Predictive animal models in all phases of ocular drug evaluation. PMID- 3332285 TI - Recent developments in chemotherapy of ocular diseases. AB - The profile of organisms responsible for ocular infections has changed over the past few decades. Although nonresistant and resistant staphylococci still lead the list, gram-negative, mixed infections and anaerobic organisms have become more evident. In spite of more potent and broader spectra antibiotics, resistant organisms still emerge. The therapy of intraocular infections requires an awareness of the latest antibiotics, particularly their advantages, limitations, toxicities, and administration. Iontophoresis through the sclera overlying the pars planum area with small diameter applicators may offer another route of administration which may reduce or eliminate the value of direct intravitreal injections of antibiotics. Reduction of the harmful effects of endotoxins of organismal origin might minimize the adverse effects of intraocular infection, particularly after gram-negative invasion. The choice of antibiotic may influence the quantities of endotoxins released. PMID- 3332286 TI - Ocular disposition of inulin from single & multiple doses of positively charged multilamellar liposomes: evidence for alterations in tear dynamics and ocular surface characteristics. AB - The effect of entrapment of inulin, a model medium molecular weight compound, in positively charged, multilamellar liposomes on ocular inulin absorption following instillation of single and multiple doses to the albino rabbit eye was studied. In spite of their affinity for the ocular surfaces, these liposomes provided 5 and 100 times lower ocular concentrations of inulin at 30 minutes post-dosing than aqueous solutions and neutral liposomes, respectively, and failed to sustain inulin concentrations in any anterior segment tissues over 120 min. This negative effect of positive liposomes on the ocular bioavailability of inulin can partly be attributed to a 2-fold faster disappearance rate from the tear pool, which more than offset their intrinsic ability to increase corneal drug permeability. For unknown reasons, multiple doses of these liposomes resulted in further reduction in ocular inulin absorption when compared with single doses. PMID- 3332287 TI - Oculotoxicities of systemically administered drugs. AB - There have been many drugs reported to cause oculotoxic responses after their systemic administration. The severity of these toxicities range from minor ocular inconvenience to permanent loss of vision. This paper reviews the current literature and attempts to suggest some probable factors involved in the development of oculotoxicities by systemic drugs. Various drug entry and exit pathways in the eye are presented and the role of some intraocular structures in the toxicity development is examined. The issues of melanin binding, genetic heterogeneity, photosensitivity and environmental pollution are discussed. PMID- 3332289 TI - [Pulmonary ventilation/perfusion ratio]. AB - The ratios of ventilatory (V) and perfusion (Q) flow rates in the lung are to a large extent responsible for the efficiency of gas exchange. In a simplified monocompartmental model of the lung, the arterial partial pressure of a given gas (Pa) is a function of several factors: the solubility of this gas in blood, its venous and inspired partial pressures and the V/Q ratio. In a multicompartemental model, the mean arterial partial pressure of the gas is a function of the individual values of Pa in each compartment as well as the distribution of V/Q ratios in the lung and the relationship between the concentration and the partial pressure of the gas. The heterogeneity of the distribution of V/Q results from those of both V and Q. Two factors are mainly responsible for this heterogeneity: the gravity and the morphometric characteristics of bronchi and vessels. V/Q ratios are partially controlled at least in low V/Q compartments since hypoxia in these compartments leads to pulmonary arteriolar vasoconstriction. However lungs V/Q ratios range from 0.1 to 10 with a mode around 1. Age, muscular exercise, posture, accelerations, anesthesia, O2 breathing, pulmonary pathology are factors which may alter the distribution of V/Q ratios. PMID- 3332288 TI - [Aldosterone as a factor of extracellular volume regulation: mechanism of action]. AB - The key role assumed by aldosterone in the regulation of extracellular volumes, requires that chloride moves along with sodium when active transport of the later ion is stimulated. In the mammalian nephron, aldosterone promotes reabsorption of sodium by the principal cells of the cortical portion of the collecting ducts. This results from hormone-induced increase in conductance for sodium at the apical pole of the target cells, and later on, from associated increased density of the sodium "pump" units at the basolateral pole. Studies carried out on amphibian epithelia indicate that chloride permeability - of mitochondria-rich cells, in all likelihood - is concurrently increased by aldosterone. It therefore looks as though this steroid hormone influences in a concerted way 2 cell populations, one being involved in transepithelial sodium transport, the other one representing the route of passage for the accompanying anion. PMID- 3332290 TI - [Physiology and physiopathology of somatic sensations studied in man by the method of evoked potentials]. AB - The physiology of somatic sensation can be investigated noninvasively in man by recording the electric activity of peripheral nerves, spinal cord and brain. Since these responses have a small voltage, it is necessary to use electronic averaging methods for improving the signal-to-noise ratio. These methods are described and discussed, as well as principles of interpretation of somatosensory evoked potentials. It is agreed that the traces thus obtained involve a series of components (extracellular potentials) which reflect distinct neural generators. These generators have been identified and localized at different levels of the subcortical somatosensory pathway and in different cortical areas. Several components reflect generators located under the recording electrodes (nearfield potentials), while other reflect extracellular potentials diffusing at a distance in the volume conductor of the neck and head (farfield potentials). The analysis of these components provides a wealth of new data for the physiology and pathophysiology of the somatic sensory system in man. Besides so-called "obligatory" components that are present irrespective of the attention of the subject, the studies have uncovered "cognitive" components which reflect neural mechanisms involved in the intellectual processus of perception and decision. PMID- 3332291 TI - [In vitro determination of the pressure-diameter relationship and velocity profiles by ultrasonic technics. In vivo application]. AB - A good knowledge of arterial flow mechanics and of the phenomena associated with fluid-boundary interactions is necessary for the determination of some fundamental parameters such as velocity, pressure and pressure-diameter relationship during a cardiac cycle. Ultrasonic techniques were developed on a test bench and directly applied to animals without major modification. On such a test bench allowing a good simulation of physiological type flows, velocity field and pressure-diameter relationship were determined. In vivo application of these techniques allowed a systematic analysis of velocity profiles in the rabbit abdominal aorta and a precise approach of rheological properties of the vascular wall. PMID- 3332292 TI - Myiasis by Wohlfahrtia vigil in nestling Microtus pennsylvanicus. PMID- 3332294 TI - Williams's force. PMID- 3332293 TI - A. R. Luria and the art of clinical biography. PMID- 3332295 TI - A note on Eric Avery's work. PMID- 3332297 TI - Tennyson, the weird seizures in The Princess, and epilepsy. PMID- 3332298 TI - Recombination nodules, synaptonemal complexes and heterochromatin in the hemipteran Triatoma infestans. PMID- 3332299 TI - Leloir, a life devoted to scientific research. PMID- 3332300 TI - Choledocholithiasis: diagnosis by ultrasound. PMID- 3332301 TI - Asthma deaths: are they preventable? AB - Asthma deaths have increased 11% between 1979 and 1982. Asthma is not a terminal condition; therefore, by definition, many of these deaths are preventable. A literature survey indicates the major causes of death from asthma to be four: 1) delays in getting/receiving appropriate care, 2) medication misuse, underuse, overuse, interaction and toxic effects, 3) receiving inappropriate care: sedation, insufficient corticosteroids, and 4) other risk factors: nocturnal asthma/morning dippers, labile and hyperresponsive airways, and infection among others. Several possible preventive measures are discussed. PMID- 3332302 TI - [Treatment of unilateral pulmonary disease in children]. PMID- 3332304 TI - CS antigen localization in malaria vectors: hypothetical refractoriness to transmission observed in the field. AB - Indoor resting Anopheles gambiae s.l. were collected in two villages near Ouagadougou, Burkina Faso, and processed to investigate the presence and distribution of Plasmodium sporozoites. Salivary glands were dissected, examined by phase contrast microscopy and further processed by IRMA in order to reveal the presence of the circumsporozoite (CS) antigen of P. falciparum. The corresponding thoraces were homogenized and processed by IRMA. In the village characterized by the higher inoculation rate more than 40% of the infected mosquitoes were not found infective since CS antigen was detected in the thorax in absence of sporozoites and CS antigen in the corresponding salivary glands. PMID- 3332303 TI - Detection of antibodies to Plasmodium falciparum sporozoites by employing synthetic peptides. AB - A new achievement in the immunodiagnosis of malaria has been reached after the knowledge of the molecular structure of some plasmodial antigens has become available. One example is given by the repetitive immunodominant epitope of Plasmodium falciparum circumsporozoite protein, which consists of 4 tandemly repeated aminoacids (Asn-Ala-Asn-Pro = NANP). A large synthetic peptide reproducing 40 NANP repeats, (NANP)40, has been shown to reproduce efficiently the native antigen in the CS protein and has been used to develop an enzyme linked immunosorbent assay (ELISA) for the detection of antisporozoite antibodies in individuals from malaria-endemic countries. This (NANP)40 ELISA has been employed in a longitudinal study in a rural community in Tanzania. The results obtained have shown (i) that the presence of anti-(NANP) antibodies is associated with a certain degree of protective immunity; and (ii) that genetic factors could play a role in the host immune responsiveness to (NANP). Such an ELISA can be easily applied to field research and can be useful for monitoring the immune status of populations participating, in the future, to malaria vaccination trials employing P. falciparum sporozoite peptides. PMID- 3332305 TI - Recent developments in the immunobiology of Pneumocystis. AB - Available data on the immune responses to Pneumocystis are discussed leading to the general conclusion that T lymphocytes and monocytic cells are involved in host defence. Recent progress in characterization of parasite antigens is reviewed with special reference to the development of monoclonal antibodies specific for Pneumocystis. PMID- 3332307 TI - [Horton's arteritis. Anatomical-clinical study of 12 cases]. PMID- 3332306 TI - Application in clinical epidemiology of new advances in immunology and molecular biology of malaria. AB - The first purpose was to study the sensitivity of a spot hybridization assay for P. falciparum with a DNA probe. This assay was compared with light microscopy for the detection of low-grade parasitemia. The second purpose was to study in clinically immune individuals the seroreactivity, against a newly identified P. falciparum antigen, deposited in the erythrocyte membrane during merozoite invasion (Perlmann et al., 1984). This antigen is considered to be a potential component in a future vaccine against the blood stage of the parasite. In a holoendemic village in Yekepa area, Northern Liberia, 28 adult men with a high degree of protective immunity against malaria, were shown to have repeatedly low grade parasitemias of varying density. The spot hybridization assay with the DNA probe was highly sensitive in detecting parasitic infection. The sensitivity was comparable to that of the examination of a blood film for about 15 min by an experienced microscopist. The seroreactivity against Pf 155 antigen varied between a high positive titer to negativity in different subjects, but the reactivity was constant over a period of 15 months for each subject despite numerous new infections and comparable protective immunity against malaria infection. PMID- 3332308 TI - [Anatomohistopathological picture of renal explants. Correlations with elementary lesions and survival of the graft]. PMID- 3332309 TI - [The senile heart]. PMID- 3332310 TI - [Methods and instrumentation for the histological study of mummified tissues]. PMID- 3332311 TI - Neurological sciences at their origin: neurology and neurological surgery in the medicine of ancient Egypt. PMID- 3332312 TI - Alpha enhancement: a comparison study of biofeedback, open focus training, and control procedures. AB - Alpha wave production has been related to affective and physiological arousal states since Berger's (1929) initial research. More recently, the possibility of subjects' control of alpha production has been investigated via the innovation of biofeedback procedures. Research conducted by Kamiya in the 1960s and others led to the early conclusion that alpha-wave production could be controlled and that such control could facilitate enhancement of a person's state of physical and psychological well-being. Subsequent research data have questioned these conclusions. The present study focused upon alpha-wave production with or without a procedure for relaxation called "open-focus training." Twenty subjects were divided into four equal groups and seen for three 20-min. sessions. Results suggested a deterioration of alpha production with all groups combined, no significant differences between the biofeedback and no biofeedback control groups (without "open-focus training"), and greater decrease in alpha production during each session in the "open-focus" groups (with or without biofeedback). These unusual results and their implications are discussed. PMID- 3332314 TI - Implications of phenomenological grounding in the "microscopic": an experiential relativity from the microcosmos. AB - The implications of phenomenological grounding in the microscopic (atomic) level of reality are discussed. In such a state the body is experienced as process within an environment organized by "infinite" time. The world-self phenomenon is experienced as coconstituted, and the feeling of individuality is replaced by the experience of intimate integration. PMID- 3332313 TI - Research on effects of color reversal on the visual perceptual and visuomotor performances of spastic cerebral palsied and other exceptional individuals. AB - Research pertaining to the effects of color-reversal (black and white) on the visual perceptual and visuomotor performances of spastic cerebral-palsied children and other exceptional individuals was examined. In general, evidence to date suggests that spastic cerebral-palsied children show significant improvement in visuomotor and visual perceptual performance with the color-reversal of the standard black-on-white figure-ground relationship in stimulus and response materials of standardized tests. PMID- 3332315 TI - A historical perspective on sleep disorders medicine. AB - The recent development of sleep disorders medicine traces its origins to the increased understanding of basic human sleep physiology gained over the past 30 years. The primary tool for diagnosis and management is the long-term polygraphic recording of multiple physiologic variables (polysomnography). A "style" of practice is emerging that is multidisciplinary and often institutionally-based in sleep disorders centers. High patient and physician satisfaction in this field indicate that rapid growth will continue. PMID- 3332316 TI - Insomnia. AB - Insomnia complaints are common in the general population and are seen with even greater frequency among psychiatric patients. In any patient, the development of insomnia complaints may reflect the combined influences of various psychological, psychophysiologic, pharmacologic, and other medical factors. The capacity to describe and define specific sleep disorders is an important component in the development of a workable plan for the treatment of these disturbances. Knowledge of specific behavioral and pharmacologic modalities is also necessary for the choice of safe and effective treatment approaches. PMID- 3332317 TI - A behavioral perspective on insomnia treatment. AB - The major behavioral treatments of insomnia--progressive relaxation, biofeedback, cognitive approaches, stimulus control instructions, chronotherapy, and sleep restriction therapy--are described. The basis of these interventions are conceptualized as issuing from the interdependence of sleep and wakefulness, the temporal organization of sleep-wake processes, cognitive effects on arousal, the role of perpetuating factors in chronic insomnia, and conditioning. A pilot study of the conditioning of rapid sleep onset with the aid of a hypnotic provides a preliminary demonstration of the application of conditioning to the pharmacotherapy of sleep. It is predicted that the commonly accepted view of sleep latency as solely reflecting physiological sleep tendency, will require modification to include the effects of conditioning. The current pattern of hypnotic usage, an issue of widespread concern, is subjected to a behavioral analysis based on a new model of conditioned tolerance. The intermittent administration of placebo within a hypnotic regimen is predicted to be especially beneficial in sustaining hypnotic efficacy. PMID- 3332318 TI - Pharmacotherapy of insomnia. AB - Sleep disturbance is often the result of specific pathophysiologies of sleep or of psychiatric illness. When this is the case, specific treatment of these conditions is indicated. When such disorders are not found, hypnotics often play a useful role, particularly as adjunctive treatment while the patient receives behaviorally-oriented therapy. Considerations in choosing a hypnotic should include issues of residual daytime effects, special problems of the elderly, interaction with alcohol, dependence, and effects on respiration. PMID- 3332319 TI - Sleep and affective disorders. A minireview. AB - The most predictable electroencephalographic sleep changes of major depression are a shortened first NREM sleep period, a prolonged first REM period (with increased density of rapid eye movements), sleep continuity disturbance, and diminished slow wave sleep (with shifting of delta activity from the first to the second NREM sleep period). The more rapid appearance of the first REM sleep period occurs in relation to sleep onset but not apparently in relation to clock time. The changes occurring in the first NREM-REM cycle of the night appear to be relatively specific to major (particularly endogenous) depression. Depressed men appear to have diminished nocturnal penile tumescence compared with healthy controls, but depressed patients generally do not have a higher incidence of sleep apnea or nocturnal myoclonus. The sleep physiologic changes of depression appear to persist into clinical remission, suggesting that they are trait-like. Published studies appear to support the conclusion that there is a close link between the regulation of sleep and the regulation of mood in affective illness. PMID- 3332320 TI - Obstructive sleep apnea syndrome. A review. AB - Obstructive sleep apnea syndrome (OSAS) is a complex disorder characterized by a sleep-related collapse of the upper airway. The most likely candidate for the common pathway linking various abnormalities casually associated with OSAS (such as adenotonsillar hypertrophy, obesity, retro- or micrognathia, acromegaly, or more subtle structural anomalies) is an abnormally small upper airway lumen. Symptoms of OSAS that appear during sleep include snoring, abnormal motor activity, disturbed nocturnal sleep, a sensation of choking, heartburn, nocturia, nocturnal enuresis, and heavy sweating. Daytime waking symptoms are dominated by often profound sleepiness, which may secondarily be associated with automatic behavior, retrograde amnesia, hypnagogic hallucinations, personality changes, sexual difficulties, and headaches. Careful evaluation, both sleeping and waking, are essential to select appropriate treatment. Treatments include nasal continuous positive airway pressure, tracheostomy, weight loss, uvulopalatopharyngoplasty, mandibular advancement, and so forth. PMID- 3332321 TI - Parasomnias. AB - This article presents four examples of parasomnia activity. Sleepwalking, sleep terror, and rhythmic movement disorder all occur more commonly in children; however, they can persist into adulthood. REM behavior disorder frequently occurs in elderly patients with neurologic lesions. The sleep stage associations of the different disorders differ. Two of the disorders, sleepwalking and sleep terrors, have a clear association with stage 3/4 sleep, and REM behavior disorder occurs in REM sleep. Rhythmic movement disorder episodes can present solely in REM sleep but more typically occur in light non-REM sleep, and there are usually voluntary episodes during wakefulness. PMID- 3332322 TI - Behavioral "insomnia" in the child. AB - Most of the causes of sleeplessness in the young child after early infancy are behavioral in nature. These may be primary or they may complicate other disorders. Typical factors include inappropriate associations to the sleep transition process, absent and inconsistent limit setting by caretakers, and various scheduling abnormalities (including unnecessary nighttime feedings). Once proper diagnosis is made, rapid resolution can be expected through behavioral intervention. Even partial arousal symptomatology ("night terrors"), often misdiagnosed at this age, may reflect, and respond to correction of, inappropriate sleeping schedules. PMID- 3332323 TI - Childhood enuresis. A comprehensive treatment program. AB - Enuresis is a common, often misunderstood, condition that affects millions of children in the United States. For most children with primary enuresis, preventing secondary psychological sequelae associated with guilt and shame is an important consideration in the decision whether or not to treat. Because the spontaneous resolution rate is 15 per cent per year, the older the child, the more important treatment becomes. It is important to distinguish primary from secondary enuresis, as most psychogenically induced enuresis is of secondary nature. A careful history can usually elicit the etiology, as well as the exacerbatory factors in both types of conditions, providing direction for treatment. Treatments include pharmacologic, behavioral, and psychotherapeutic. In some cases, surgical intervention of either a urologic or otolaryngologic nature is indicated. A multidimensional approach is often best, and we have described our program with its success rate. Treating the enuretic child can be frustrating, but is usually quite gratifying for the child, parents, and the clinician. PMID- 3332324 TI - Dream anxiety attacks (nightmares). AB - Nightmares--disturbances of dreaming sleep experienced at some point in time by most patients--are often seen in adults as a consequence of physical or emotional trauma. The presence of nightmares on a chronic basis in adult life may reflect specific personality characteristics and may define a population at risk for other psychiatric disturbances. Treatment, if indicated, may include psychotherapy and pharmacotherapy, with the regimen determined by the patient's specific history and symptoms. PMID- 3332325 TI - Evaluation of impotence. Monitoring periodic penile erections during sleep. AB - The monitoring of periodic penile erections during sleep has helped alter the understanding and treatment of impotent patients. The reasons why this has occurred, the procedures used in monitoring sleep erections, and the validation of the procedures are reviewed. PMID- 3332326 TI - Biologic rhythm disorders, depression, and phototherapy. A new hypothesis. AB - Disturbances of the circadian timing system are implicated in the pathogenesis of numerous clinical syndromes, including sleep and affective disorders. Abnormalities of circadian rhythms can now be directly measured in the clinical laboratory and potentially corrected. Sleep scheduling disorders are most commonly due to phase misalignments between the endogenous circadian pacemaker and the socioenvironmental schedule. Current research is increasing our understanding of the influence of bright light exposure on the circadian timing system and has begun to be used successfully in the management of these conditions. There is substantial evidence that abnormalities of the circadian timing system are associated with depression. However, the application of new biologic rhythm diagnostic techniques would be required to establish whether circadian dysfunction is involved in the pathogenesis of these conditions. We propose a new hypothesis that phototherapy for seasonal depression may act by increasing an abnormally low circadian amplitude in those patients, such as that reported in endogenously depressed patients. The powerful effect of light on the circadian system indicates that phototherapy may become an important tool in the management of disorders of circadian etiology. PMID- 3332327 TI - Vulvovaginitis in the child and adolescent. PMID- 3332328 TI - Adverse effects of overdosage of vitamins and minerals. PMID- 3332329 TI - Recognition of sexual abuse in children. PMID- 3332330 TI - Bee, wasp, and hornet stings. PMID- 3332331 TI - Mushroom poisoning: identification, diagnosis, and treatment. PMID- 3332332 TI - Constipation in children. PMID- 3332333 TI - Acute ataxia. PMID- 3332334 TI - Recurrent headaches in children: diagnosis and treatment. PMID- 3332336 TI - Variations in normal sexual development. PMID- 3332335 TI - The difficult child. PMID- 3332338 TI - Guillain-Barre syndrome in children. PMID- 3332337 TI - Evaluation of chest pain in children. PMID- 3332339 TI - Vulnerable child syndrome and its variants. PMID- 3332340 TI - Magnetic resonance imaging. PMID- 3332341 TI - Intrauterine growth retardation. PMID- 3332342 TI - Psychiatric sequelae of severe closed head injury. PMID- 3332343 TI - Fetal alcohol syndrome. PMID- 3332345 TI - Behavioral and developmental components of child health promotion: how can they be accomplished? PMID- 3332344 TI - School refusal. PMID- 3332346 TI - Genes, syndromes, and cancer. PMID- 3332347 TI - Dermatology potpouri. PMID- 3332348 TI - A child's reactions to parents' problems. PMID- 3332349 TI - Iron supplementation in infancy. PMID- 3332350 TI - Management of nonfebrile seizures. PMID- 3332351 TI - Progressive weakness in infancy and childhood. PMID- 3332352 TI - Discipline and permissiveness. PMID- 3332353 TI - Prognosis of attention deficit disorder and its management of adolescence. PMID- 3332354 TI - Tic disorders in childhood. PMID- 3332355 TI - The child with persistent cough. PMID- 3332356 TI - School placement. PMID- 3332357 TI - Oral rehydration therapy and dietary therapy for acute childhood diarrhea. PMID- 3332358 TI - Conversion reactions in adolescents. PMID- 3332359 TI - Mental retardation. PMID- 3332360 TI - Physical examination of sexually abused children and adolescents. PMID- 3332361 TI - Cyanosis in the newborn. PMID- 3332362 TI - Assessment of renal function in newborn infants. PMID- 3332363 TI - Growth failure in infancy. PMID- 3332364 TI - Sleeplessness, night awakening, and night crying in the infant to toddler. PMID- 3332366 TI - Cardiac causes of syncope. PMID- 3332365 TI - Myocarditis in children. PMID- 3332368 TI - Sickle cell diseases: diagnosis and management in infancy and childhood. PMID- 3332367 TI - Ulcerative colitis and Crohn disease in children. PMID- 3332369 TI - Acute respiratory infections in children: etiology and epidemiology. PMID- 3332370 TI - Complications of cardiac surgery in children. PMID- 3332371 TI - Nutritional management of children and adolescents with insulin-dependent diabetes mellitus. PMID- 3332372 TI - Diagnosis of deafness in infancy. PMID- 3332373 TI - Preparticipation evaluation for athletics. PMID- 3332374 TI - Female athletes. PMID- 3332376 TI - Nonimmune hydrops fetalis. PMID- 3332375 TI - Respiratory syncytial virus infections in infants and children: diagnosis and treatment. PMID- 3332378 TI - [Submerged-phase gel electrophoresis in the analysis of plasmids for epidemiologic purposes]. AB - The validity of the submarine agarose gel electrophoresis as routine method for plasmidic epidemiology was considered. Using standard plasmids, the efficiency of a performed protocol conditions (5 V/cm for 3 hours, 0.8% agarose) in screening plasmids of different size was studied. The results provide sharp profile resolution and an accurate estimate of molecular weights in the range from 1.2 to 112 megadaltons. PMID- 3332377 TI - [Carcinoembryonic antigen in a review of cases in the literature]. AB - Literature analysis of CEA serum levels tested in 21,147 patients, with non neoplastic and neoplastic disease of various organs, are reported. The sensitivity, the specificity, the positive and negative prognostic trend and the effective value of test in different pathologic situations are evaluated on the basis of organ localization and embryological origin. PMID- 3332379 TI - [ABACTO-SCREEN: a new system for the rapid screening of bacteriuria. Evaluation of the precision versus the traditional methods and compared with the Abbott MS 2]. AB - ABACTO-SCREEN is an automated turbidimetric system for rapid screening of bacteriuria composed by a multichannel photometric instrument and an original disposable. In this study the system has shown good sensitivity (6.9% of false negative results on the true positives) and specificity (22.4% of false positive results on the true negatives) when on assuming 100,000 colony forming units (CFU)/ml as a threshold of positivity. Comparison with Abbott MS-2 has revealed better performances for sensitivity and comparable specificity. False negatives analysis has revealed probable influence of anaerobic bacteria in the plate counting or slowing in culture broth growth cause by antimicrobial substances in urine samples. PMID- 3332380 TI - [Regulation of the immune response mediated by cellular interactions. Its relation to anti-tumor immunity]. PMID- 3332381 TI - [Saccharomyces cerevisiae: porphobilinogenase activity in a wild-type strain and its heme-deficient mutant]. AB - Properties of Porphobilinogenase (PBGase), the enzyme complex converting porphobilinogen (PBG) into uroporphyrinogens, were comparatively studied in a wild strain D273-10B and its mutant B231 of Saccharomyces cerevisiae, Figure 1 shows the growth curves for both strains. The basic pattern of growth was observed but, although S. cerevisiae is a facultative aerobe and was grown on dextrose, a diauxic growth curve was not observed. The beginning of the exponential phase was slightly delayed for the mutant, so, its generation time (G = 3.20 h) was greater than that for the wild strain (G = 1.26 h). Optimum conditions for extracting the enzyme from both strains were found to be sonication at 10 mu for 3 min (Table 1). Table 2 shows the effect of centrifugation at 24,000 xg for 30 min on activity. For both strains the amount of porphyrins formed was the same either in the absence or presence of air. It was found (Figure 2) that urogen formation was linear with protein over a wide range of concentrations and with incubation time up to 2h in agreement with previous results for the enzyme of different sources. Figure 3 shows the effect of pH on PBGase activity. An optimum pH of 7.4 was found for both strains employing sodium phosphate buffer pH 8.0. The shape of the pH curve as well as optimum pH were the same in both Tris-HCl and phosphate buffer, however PBGase was 15% less active in the former. When plots of velocity against PBG concentration were analyzed for PBGase, it was found that measuring the rate of the reaction on the basis of total urogen formation, saturation curves for wild and mutant strains harvested at the exponential phase, followed classical Michaelis-Menten kinetics. Saturation was reached at PBG concentration of about 70-90 microM. Therefore, double reciprocal plots (Figure 4) were linear and from these plots apparent Km's values of 20 and 14 microM were obtained for the wild and mutant strain respectively. It is known that in some organisms, the activity of the enzyme of heme synthesis is significantly influenced by the days of growing; therefore the effect of time growing on PBGase activity was studied (Figure 5). A well defined maximum of enzyme activity was observed for the mutant strain after 20h of growing; while activity of wild strain did not significantly vary during growth. PMID- 3332382 TI - Synthetic trypanocides: growth-inhibiting properties of new 1,2,3,4 tetrahydrocarbazoles on Trypanosoma cruzi. AB - Several new 1,2,3,4-tetrahydrocarbazole, 5,6-dihydrobenzo(alpha) carbazole, 3 methylindole and substituted benzimidazolyl compounds were synthesized and assayed for their action on growth of Trypanosoma cruzi, cultured in Warren's liquid medium. 6-chloro and 6,8-dichloro-N-(1-ethyl-N-diethylamino)-1,2,3,4 tetrahydrocarbazole++ fumarate resulted the more active in inhibiting growth of the parasite. The new compounds were apparently more effective than those prepared previously by Poliakoff et al. (5). PMID- 3332384 TI - [Comparison of the efficiency of 2 culture media in the recovery of heterotrophic bacteria damaged with chlorine]. AB - In this study, culture mediums R2A and m-HPC were compared with respect to their efficiency in the recuperation of injured heterotrophic bacteria present in water, which previously was treated with chlorine. The results of total counts obtained by membrane filtration, show that medium R2A was better than m-HPC. These two culture mediums are indicated by the 16th edition of Standard Methods for the Examination of Water and Waste-water. The results obtained may be due to the low concentration of organic matter, or to the presence of yeast extract in the R2A medium. PMID- 3332385 TI - The effects of ionizing radiation on structure and function of DNA. PMID- 3332383 TI - [Production of thermolabile exotoxin by strains of Escherichia coli isolated in Argentina]. AB - The production of heat-labile enterotoxin (LT) by E. coli strains was studied. Four strains isolated from acute infant diarrhea cases in Argentina and one reference strain, all of them producers of different levels of LT, were employed. GM1-ELISA was used as titration method. The production was assayed in two culture media; Evans (Ev) and Trypticase Soy Broth (CTS) with or without glucose and with different concentrations of lincomycin (0; 30; 45 y 90/micrograms/ml). The effects of pH and inoculum concentration were also examined. Higher levels of LT were found to be produced in Ev (mean production value X = 233.1 ng/ml) than in CTS (X = 133.8 ng/ml), although the difference was statistically not significant (P = 0.22). Lincomycin addition stimulated toxin synthesis and release in both media, and these effects were found to increase with the concentration of the antibiotic (P less than 0.01). Glucose increased the LT levels of low-producing strains and also the growth rate, cellular yield and LT levels of 40T and CC2e strains. Levels of LT released were found to be independent of inoculum concentration. In CTS without pH control, the LT production was one half the levels attained with regulated pH. This was not an effect on the release of the toxin as the determination included both the extracellular LT and the intracellular toxin accumulated in the periplasmic space, which is released by polymyxin B treatment. A pH-dependent inactivation of the synthetized and release toxin was demonstrated. PMID- 3332386 TI - Why do globular proteins fit the limited set of folding patterns? PMID- 3332387 TI - The biological activities and uses of recombinant granulocyte-macrophage and multi-colony stimulating factors. PMID- 3332388 TI - Current therapy for diffuse large-cell lymphoma. PMID- 3332389 TI - Monoclonal antibodies: their use in bone marrow transplantation. PMID- 3332390 TI - Alternative approaches to transfusion: autologous blood and directed blood donations. PMID- 3332391 TI - Evaluation and use of laboratory instrumentation for office hematology procedures. PMID- 3332392 TI - In vivo assessment of thrombosis and fibrinolysis during acute myocardial infarction. PMID- 3332393 TI - Management of patients refractory to platelet transfusion--an evaluation of methods of donor selection. PMID- 3332394 TI - The effect of therapy on the mental health of the elderly. AB - This research synthesis was undertaken to study the effects of treatment on the mental health of elderly people. Forty-one controlled studies were analyzed using meta-analytic techniques. Type of treatment along with subject, therapist, setting, and methodological characteristics of the studies were identified and their contributions to mental health outcomes measured. Results indicated that the mean outcome of the experimental group, treated with any type of treatment improved from the fiftieth percentile to the seventieth percentile relative to the mean of the untreated control groups. This research synthesis supports the belief that, in general, treatment is effective in enhancing the mental health of the elderly. PMID- 3332395 TI - [The role of costochondral grafts in the treatment of ankylosis of the maxillary joint]. PMID- 3332396 TI - [Ovarian cancer and pregnancy]. PMID- 3332398 TI - [Current status and problems posed by human brucellosis]. PMID- 3332397 TI - [Animal brucellosis in tropical Africa. Epidemiological, clinical and bacteriological characteristics]. PMID- 3332400 TI - [Serologic diagnosis of human brucellosis in Benin]. PMID- 3332401 TI - [Medical prevention of animal brucellosis]. PMID- 3332402 TI - [Treatment of human brucellosis]. PMID- 3332399 TI - [The ELISA reaction in the diagnosis of animal brucellosis]. PMID- 3332403 TI - Markers of aging. Modeling the clocks that time us. PMID- 3332404 TI - Board and care housing. An analysis of state differences. PMID- 3332405 TI - Delivering health care to the elderly. The development and validation testing of a typology of problems. PMID- 3332406 TI - Magnetic resonance imaging of the central nervous system: interpretation and normal anatomy. PMID- 3332407 TI - MR + ESME = MESMER. PMID- 3332408 TI - Magnetic resonance imaging in adult white matter disorders and hydrocephalus. PMID- 3332409 TI - Magnetic resonance imaging of brain tumors. AB - Since MR is a new imaging modality, a major question to answer is, "What is the role of MRI in relation to older, more traditional diagnostic techniques?" Several studies comparing CT and MRI for brain evaluation have shown MRI to be more sensitive, although not more specific. The advantages of MRI center around its ability to reveal abnormalities that may not be detectable or only poorly seen on CT. In cases in which only a nonspecific mass effect may be depicted on CT, the MR may define the precise extent and location of a tumor. Furthermore, MRI with its increased contrast discrimination and its ability to obtain images in many planes can better define the precise location of a lesion relative to key neuroanatomic structures. This is extremely important for optimal surgical and radiotherapy planning. The disadvantages of MRI include the fact that small calcifications cannot be seen and one cannot yet evaluate the presence of an altered blood-brain barrier. Despite these disadvantages, we feel that MRI should be the primary study for diagnosis of brain abnormalities. When an abnormality is detected and further information is desired, a complementary CT study should be performed in order to evaluate areas of blood-brain barrier alteration and the presence of abnormal calcification. PMID- 3332410 TI - Brain edema studied by magnetic resonance. PMID- 3332411 TI - Magnetic resonance imaging of the brain in childhood. PMID- 3332412 TI - Magnetic resonance imaging of the posterior fossa and brainstem. PMID- 3332413 TI - Magnetic resonance imaging of the spine. AB - MRI of the spine is an accurate, noninvasive sensitive imaging modality for the spine capable of demonstrating many pathologic conditions. Its ability to demonstrate long segments of the spine as well as its multiplanar imaging capability offer a unique anatomic perspective. It has superior contrast resolution without the use of iodinated contrast material and uses no ionizing radiation. By manipulating pulse sequences (TR and TE), differences in T1 and T2 relaxation rates can be made manifest, allowing differentiation of anatomic structures and in many cases pathologic conditions. Imminent and future improvements in slice thickness, spatial resolution, and signal-to-noise ratio are likely to improve further its sensitivity and accuracy as an imaging modality. PMID- 3332414 TI - Magnetic resonance in neuromuscular disorders. PMID- 3332415 TI - Neuro-ophthalmologic complications of hydrocephalus and shunting procedures. PMID- 3332416 TI - The orbit and neuro-ophthalmology. PMID- 3332417 TI - Isolated third nerve palsies. AB - In the diagnostic assessment of patients with N III palsies, the examiner should first endeavor to determine if the palsy is isolated, that is, unassociated with other contributory neurologic findings. If any other abnormalities are present, they should be used to localize the lesion and to help direct ensuing neuroradiologic studies. If the palsy is isolated, the presence of pupil sparing, together with advanced age or a vasculopathic background probably indicates that an extra-axial infarction of the nerve has taken place. The patient may safely be observed periodically without radiographic studies. In younger patients or those without significant vasculopathy, the status of the pupil should not be a major determinant of management. Moreover, the clinician must be aware that pupil sparing is expected when the vulnerable superior division of N III is selectively involved in cavernous sinus compressive lesions. "Pseudo pupil-sparing" in aberrant N III regeneration and in coexisting parasympathetic and sympathetic pupillomotor paresis is a pitfall to be avoided. When one of the muscles subserved by N III appears to be misfunctioning, the diagnosis is rarely that of a partial N III palsy. Instead, the causative lesion is more likely to be in the muscles themselves, the neuromuscular junction, or in the gaze pathways converging on the N III subnuclei. PMID- 3332418 TI - Diplopia and sixth nerve palsies. PMID- 3332419 TI - Vertical diplopia. AB - At this point, it is customary for all hands to gather round the old decision tree and whittle on a few algorithms. Because I have been chastened by occasional painful falls from slippery decision branches, however, I must make do with a short reprise. Some nodal points in analyzing vertical diplopia include: (1) evidence of central nervous system involvement; (2) pupillary sparing; and (3) the presence of proptosis of orbital congestion. As endlessly stated, premature closure of the differential diagnosis should be avoided and the tendency to diagnose partial third nerve palsy staunchly resisted. However, all of this will probably be of little comfort to you when you face your next lethargic patient who has small angle diplopia and speaks one of the obscure rural dialects of Freedonia. PMID- 3332421 TI - Visual obscurations: evanescent and elementary. PMID- 3332420 TI - Supranuclear disorders of horizontal eye motion. PMID- 3332422 TI - Diagnosis and management of vision-threatening papilledema. PMID- 3332423 TI - Ocular complications of atherosclerosis: what do they mean? PMID- 3332424 TI - The role of carotid noninvasive tests in stroke prevention. AB - The evaluation of carotid disease is now in turmoil. Part of the problem stems from uncertainty over old issues, such as the role of carotid endarterectomy in the treatment of asymptomatic patients with high-grade carotid stenosis. Part of the problem results from the recent increase in sensitivity of certain carotid noninvasive tests and uncertainty about their role in the rational evaluation of a patient with suspected carotid disease. Finally, at this point, we do not know the true natural history of severe carotid stenosis, plaque ulceration, or wall hemorrhage, although retrospective studies and histologic data imply that these factors increase an individual's risk of stroke. Physicians caring for patients with carotid atherosclerotic disease may find themselves in the unusual situation of having more information from a panel of noninvasive tests than they can analyze. The fault does not lie with noninvasive testing itself, of course, but with our previous dependence on arteriography for anatomic information and the difficulties inherent in obtaining natural history data about any disease process for which there is surgical therapy. PMID- 3332425 TI - Optic nerve disorders. PMID- 3332427 TI - The key to the brain. Felix Vicq d'Azyr (1748-1794). PMID- 3332428 TI - Reduction of stroke through risk factor modification. PMID- 3332426 TI - Visual evoked potential: enhancing its utility. AB - The VEP can be used to assess the contributions of specific neuronal populations to visual processing heretofore evaluable only by microelectrode or psychophysical techniques. The first approach is not feasible in humans. The second is exquisitely sensitive and reliable when trained observers are studied. Psychophysical methods are subjective, requiring subject cooperation and understanding of threshold detection. These studies are often prolonged, with results inconsistent among patients in the clinic. The VEP offers an objective assessment of visual performance and permits quantification of deficits in acuity, contrast, and adaptation (especially when real-time retrieval is used), when one measures more than the latency. PMID- 3332429 TI - Diagnostic approaches to cerebrovascular disease. PMID- 3332430 TI - Asymptomatic carotid bruit and stenosis. PMID- 3332432 TI - Stroke due to cardiogenic embolism. PMID- 3332431 TI - Miscellaneous cerebrovascular conditions. PMID- 3332433 TI - Platelet function and antiaggregant therapy in ischemic stroke. PMID- 3332434 TI - Controversies in aneurysm surgery. PMID- 3332435 TI - Antifibrinolytic therapy for prevention of recurrent aneurysmal subarachnoid hemorrhage. PMID- 3332436 TI - Surgical treatment of cerebrovascular occlusive disease. AB - Surgical therapy for cerebrovascular occlusive disease has a rich and fascinating history. Carotid endarterectomy is the most commonly performed operation for cerebrovascular disease. Other ingenious efforts have been tried and, of these, only the superficial temporal middle cerebral artery bypass procedure has been prospectively studied. All efforts at extracranial and intracranial vascular surgery are under scrutiny presently and many feel that the extracranial intracranial bypass procedure has little, if any, future. The efficacy of carotid endarterectomy will probably be studied prospectively, but, for the immediate future, endarterectomy is a well-established therapy for certain cases of carotid stenosis or ulceration. PMID- 3332437 TI - Management of stroke in the intensive care unit. PMID- 3332439 TI - Anatomy of the lumbar vertebral column. PMID- 3332438 TI - The great names of our profession. Robert Bentley Todd (1809-1860). PMID- 3332441 TI - Upon the wracke of this tough world. Traction as treatment or torture. PMID- 3332440 TI - Lumbar spinal stenosis. PMID- 3332442 TI - Evaluating the perplexing neuropathic patient. PMID- 3332443 TI - The search for Sottas, Part I, The Woods. PMID- 3332444 TI - Diabetic polyneuropathy. PMID- 3332445 TI - Polyneuropathies associated with plasma cell dyscrasias. PMID- 3332447 TI - Autonomic neuropathy. PMID- 3332446 TI - Acquired demyelinating polyneuropathies. PMID- 3332448 TI - Sensory neuronopathy. PMID- 3332449 TI - Compression neuropathies. AB - Nerve compression, frequently from entrapment at specific anatomic locations, is a common clinical entity, especially in patients with predisposing occupations or with certain medical disorders. It should be pointed out that a nerve can be compressed at more than one level. Early recognition and treatment are the most effective means of preventing long-lasting disability, since, despite the capacity for regeneration bestowed on the peripheral nervous system, functions lost as a result of denervation are never fully restored. PMID- 3332450 TI - Nerve regeneration. PMID- 3332451 TI - Toxic neuropathies. PMID- 3332452 TI - Drug therapy for ischemic stroke. PMID- 3332453 TI - Practical therapy of Parkinson's disease. PMID- 3332454 TI - Drug treatment of hyperkinetic movement disorders. PMID- 3332455 TI - Treatment of Wilson's disease. PMID- 3332456 TI - "First a little..." (homeopathic dosing). PMID- 3332457 TI - Normal sleep: patterns and mechanisms. AB - In the last three decades, research in the sleep laboratory has decisively contributed to a much deeper knowledge of sleep physiologic and pathologic states. Parallel to clinical research related to sleep disorders, multifaceted basic research has greatly contributed to a better understanding of the mechanisms underlying sleep and wakefulness. This basic research in the realm of the neurosciences integrates data derived from the application of various methodologic approaches. Currently, the prevailing concepts about sleep mechanisms generally favor the idea of a dynamic interaction among systems rather than that of a unidimensional explanation for sleep generation. Examples of these integrative concepts in current sleep research are the revised model of reciprocal interaction for the control of REM sleep and the two-process model comprising the seemingly incompatible homeostatic and circadian sleep mechanisms. In sleep disorders medicine, the prevailing approach is also integrative: findings from the sleep laboratory are considered in conjunction with those from clinical experience in understanding the nature of sleep disorders. Applying this integrative model, physicians in sleep disorders medicine are able to manage patients with sleep disorders comprehensively. Based on an understanding of sleep physiology, clinicians can make the diagnosis of most sleep disorders in the office setting. PMID- 3332458 TI - Nosology and prevalence of sleep disorders. AB - Although the initial sleep disorders classifications provided a framework for categorizing diagnoses, these early instruments had a number of limitations. Among their shortcomings were a lack of specific diagnostic criteria, limited clinical validation, and an overreliance on sleep laboratory findings. As a result, many of the diagnoses were not only poorly substantiated, but they lacked clinical relevance. Also, because of a fusing of diagnoses, a causal relationship was implied that may have been nonexistent and could misdirect the treatment focus. The ICD-10 represents a clinically based diagnostic classification. Furthermore, this classification system includes diagnostic criteria and encourages multiple diagnoses for a more complete description of the patient's clinical presentation. In addition, the ICD-10 allows for differentiation of psychogenic, developmental, and organic factors. Finally, it can be fully applied in the office setting, which allows physicians to maximize their interviewing and assessment skills to complete the diagnoses and subsequent treatment plans. Thus, this classification system strongly reinforces the doctor-patient relationship. It also facilitates consideration of the entire scope of the patient's problems in a truly biopsychosocial perspective. The prevalence of insomnia ranges across studies from 20 to 30% of the adult population. Before adulthood, its prevalence is below 2%. About 5% of adults complain of excessive daytime sleepiness. Among the conditions of excessive daytime sleepiness, narcolepsy has a prevalence of 0.1% and sleep apnea not more than 1% in the general adult population. Nightmares have a prevalence of about 5% in adulthood and 20% in childhood. Sleepwalking and night terrors have a prevalence of less than 1% in adulthood and 15 and 5%, respectively, in childhood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332460 TI - Disorders of excessive sleepiness: narcolepsy and hypersomnia. AB - Besides sleep apnea, the main disorders of excessive daytime sleepiness include narcolepsy and hypersomnia. Narcolepsy is characterized by periods of irresistible sleepiness and sleep attacks of brief duration and, most often, by one or more of the auxiliary symptoms: cataplexy, sleep paralysis, and hypnogogic hallucinations. Generally, sleepiness and sleep attacks in hypersomnia are of longer duration and are more resistible than in narcolepsy; also, the auxiliary symptoms are absent. There are three types of hypersomnia: idiopathic, secondary, and periodic. Nocturnal sleep is typically disrupted in narcolepsy, whereas in idiopathic hypersomnia it is prolonged and in secondary hypersomnia it is variable. The exact causes of narcolepsy and idiopathic hypersomnia are unknown; however, there is evidence for genetic predisposition for either disorder. In secondary hypersomnia causative factors include: neurologic, such as head injuries, cerebrovascular insufficiency, and brain tumors; general medical, such as metabolic disorders, various intoxications, and conditions leading to brain hypoxia; and psychiatric, most notably depression. Although the cause of periodic hypersomnia is unclear, most research supports the notion of underlying organic disease. Often, the evaluation of patients with excessive daytime sleepiness can be completed in the office setting, based on the sleep history and a thorough neurologic, general medical, and psychiatric assessment. Whenever indicated, ancillary laboratory studies, such as computed tomography and magnetic resonance scans, should be performed. Sleep laboratory recordings generally are not necessary unless there is suspicion of sleep apnea or narcolepsy in the absence of auxiliary symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332459 TI - Evaluation and diagnosis of sleep disorders patients. AB - Using the biopsychosocial model, physicians can thoroughly assess patients with sleep disorders in the office setting. A careful sleep history, drug history, general medical assessment, and psychiatric evaluation along with an appraisal of the interplay between the patient's condition and his environment can provide all of the elements needed for diagnosis and treatment formulation. The main components of the sleep history include: defining the specific sleep problem, assessing the disorder's clinical course, differentiating between sleep disorders, evaluating the sleep-wakefulness patterns, questioning the bed partner, and obtaining a family history of sleep disorders. The drug history provides important information regarding the role of various medications, which may cause sleep difficulty during their administration or following withdrawal. Implementing a complete medical assessment is necessary for the identification of certain medical conditions that may be associated with sleep disorders. Finally, a thorough psychiatric evaluation and assessment of the psychosocial consequences of the patient's disorder should be conducted. In general, sleep laboratory diagnostic studies are of limited usefulness. These studies are indicated primarily when sleep apnea is suspected or when the sleep attacks of narcolepsy are present in the absence of auxiliary symptoms. PMID- 3332461 TI - Sleep-related respiratory disorders. AB - Sleep-induced narrowing of the upper airways underlies the widespread and supposedly trivial complaint of snoring, which may not only constitute a risk factor for the cardiocirculatory system, but in predisposed individuals may lead to the OSAS. The latter is a life-threatening condition characterized by repeated episodes of cessation of respiration at night with an associated drop in SaO2. Patients frequently present with hypersomnia, systemic and pulmonary hypertension, and even heart failure. HSD is the term we use to describe the evolutive stages from snoring to OSAS. ICAH, or Ondine's curse, is the clinical syndrome of sleep-related respiratory insufficiency in the absence of airway stenosis. We do not consider central sleep apnea to be an independent disorder. For the treatment of HSD, weight reduction should be attempted first. Also, if there are malformations in the upper airway, they should be surgically corrected. The use of various medications has been rather discouraging, and CPAP and other devices that are intended to overcome the obstruction are poorly tolerated by patients. The most effective surgical treatment for OSAS, even in progressed stages of the disease, is tracheostomy. PMID- 3332462 TI - Episodic sleep disorders (parasomnias). AB - In the vast majority of patients with parasomnias, the evaluation can be accomplished in the office setting, based on information from the patients themselves and family members or other observers of the nocturnal events. Parasomnias are episodic sleep disorders that include sleepwalking, night terrors, and nightmares. All three conditions are more prevalent in childhood, when developmental factors appear to be responsible for their occurrence; in the much less frequent cases of a delayed onset or persistence in adulthood, psychopathologic states are often primary in their cause. Based on a number of clinical, physiologic, and etiopathogenetic similarities between sleepwalking and night terrors, these two conditions appear to fall along the same pathophysiologic and therefore nosologic continuum. They are both disorders of impaired arousal, characterized by various degrees of confusion, and they occur early in the night when slow-wave sleep predominates, whereas nightmares may occur at any time of the night, because they are closely associated with REM sleep. Another important issue relating to the assessment of parasomnias is to differentiate between nightmares and night terrors: in addition to the different time of night for their occurrence, nightmares are accompanied by much less anxiety, vocalization, motility, and autonomic discharge. Also, nightmare patients usually have vivid and elaborate recall for the event, whereas patients with night terrors are typically amnesic for their episodes, as are patients who sleepwalk. A mainstay in the management of sleepwalking and night terrors is instructing the patients and their family members to provide for adequate safety measures to prevent accidents that may occur during these events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332463 TI - Neurologic disorders and sleep disturbances. PMID- 3332464 TI - Clinical neuropharmacology of sleep disorders. AB - Within the context of the comprehensive treatment of sleep disorders, which includes medical, neurologic, psychiatric, and social interventions, use of medication is often indicated. Among the three benzodiazepine hypnotics that are available in the United States for the treatment of insomnia, flurazepam is effective for both sleep induction and maintenance, and it retains most of its efficacy over a 4-week period of nightly administration; temazepam is effective only for sleep maintenance, and triazolam improves both sleep induction and maintenance with initial but not with continued administration. Rebound phenomena are more frequent and intense with the more rapidly eliminated drug, triazolam, and to a lesser degree with temazepam. Also, with triazolam, certain behavioral side effects, such as amnesia and psychotic-like symptoms, have been reported. With flurazepam, which is a slowly eliminated benzodiazepine, daytime sedation is more frequent than with the other two drugs. When insomnia is secondary to major depression, antidepressant medication should be administered. Methylphenidate, amphetamines, or other stimulant medications are used for the symptomatic treatment of the sleepiness and sleep attacks of narcolepsy and hypersomnia. For cataplexy and the other two auxiliary symptoms of narcolepsy, imipramine or other tricyclics are the drugs of choice. Protriptyline and medroxyprogesterone have been used in treating mild cases of obstructive sleep apnea, but their efficacy is limited. Similarly, for the treatment of central sleep apnea, medroxyprogesterone and acetazolamide have shown only limited effects. Medication for patients with sleepwalking, night terrors, or nightmares should be prescribed judiciously, and primarily when treatment of an underlying psychiatric condition is desired. The neuropharmacology of sleep should also consider drugs that may cause sleep disorders. Medications with sleep disturbing effects include various antihypertensives, bronchodilators, and the energizing antidepressants. Withdrawal of REM-suppressant drugs, such as the barbiturates, may cause nightmares in association with a REM rebound. Occasionally, a drug or a combination of drugs may produce somnambulistic-like activity in some patients. PMID- 3332465 TI - Bell, Bach, and Campbell. PMID- 3332466 TI - Dizziness. PMID- 3332468 TI - Outpatient care of the stroke patient. AB - With fewer patients being admitted to the hospital and more therapeutic options becoming available for stroke care, an increasing number of management decisions will need to be made on outpatients. The challenge of outpatient stroke care is caring for the total patient. The neurologist should view stroke as a dynamic process, often the result of several risk factors and the cause of other problems. The hectic pace of office practice can make full assessment of the patient difficult and state-of-the-art management a formidable goal. PMID- 3332467 TI - The neurologist's approach to alcoholism and drug abuse: outpatient care. PMID- 3332469 TI - Poststroke neurobehavioral syndromes. PMID- 3332470 TI - Outpatient management of multiple sclerosis patients. PMID- 3332471 TI - Neurologists look at driving and lapses of consciousness. PMID- 3332472 TI - Cool heads and hot spots: surface thermometry and neurothermography. PMID- 3332473 TI - Determination of a hepatic volumetric index by ultrasonic scanning. AB - A prospective study was carried out to calculate, by a fast and simple ultrasonic method, the size of the liver. Seventy-five normal subjects, 38 men and 37 women, average age 51 +/- 17 years (range 19-85) were studied. The three main diameters of the liver, breadth, thickness, and height, were obtained using a compound scan technique; each diameter was measured at its largest dimension. These measurements were multiplied together and the product arbitrarily divided by 27, which is the cube of the three diameters. This yielded the hepatic volumetric index (HVI), which was between 95 and 140 in 95% of normal subjects below 65 years of age and ranged from 80 to 135 in those above 65 years. These last data proved to be in accordance with the well-known involution of liver size in the elderly and with our retrospective study on 207 normal subjects. Then, using the criteria previously proposed by us, the population studied in the prospective study was divided into three groups of morphotypes: endomorphs, ectomorphs, and mesomorphs. The ectomorphs had an HVI slightly lower than that of the endomorphs. This HVI determination, based on standardized measurements and on a statistically controlled method, allows us to separate normal from pathological livers in 10 min and plays an important part in day-to-day clinical practice. PMID- 3332474 TI - Intraoperative echotomographic diagnosis in abdominal and neurosurgery. AB - In many clinics, intraoperative sonography is used as a routine method in general surgery as well as in neurosurgery. The availability of sterilizable applicators in diverse shapes and sizes enables the optimal approach to the site to be examined. In processes involving the liver, the pancreas, the kidneys, or the brain, ultrasonic examination, together with an exact topographic localization, proved to be helpful in determining the dimensions of an altered structure. In patients with colorectal carcinoma, the discovery of metastases that had not been previously detected by percutaneous sonography proves the necessity of regular intraoperative ultrasonic examination to augment staging accuracy in tumor surgery. PMID- 3332475 TI - Endoscopic management of choledochocele. A case report and review of the English literature. AB - Choledochocele or type III choledochal cyst is a rare lesion of the biliary tree. It may be of acquired or congenital etiology and can assume one of two anatomic variants. Either the common bile duct and the pancreatic duct enter the choledochocele together, or it is formed by the common bile duct alone with the pancreatic duct entering as a separate opening. The most frequent presenting symptoms are abdominal pain, pancreatitis, and jaundice. Traditional therapy has been either marsupialization of the cyst into the duodenum or complete surgical excision. This paper cites the eighth patient reported in the English-language literature whose choledochocele was treated endoscopically. It is the authors' opinion that either an endoscopic papillotomy or an endoscopic fistulotomy with extension of the incision over the cyst is the simpler and preferred method of treatment. PMID- 3332476 TI - Long-term results of Troidl's technique of endoscopic pneumatic dilatation for achalasia of the esophagus. A prospective clinical trial. AB - In a prospective clinical trial, 26 consecutive patients underwent endoscopic pneumatic dilatation over a 10-year period. Dilatation was achieved by means of a balloon attached to a normal gastrointestinal fiberscope. With the endoscope in an inverse position, the device was placed in the cardia and the dilatation process was monitored macroscopically. Before dilatation, patients suffered from dysphagia (92%), reduced speed of swallowing (100%), symptom aggravation under stress (73%), weight loss (50%), aspiration, pain, regurgitation, and vomiting. After dilatation and long-term follow-up (mean of 5 years), symptoms could be markedly reduced, especially the speed of eating and symptom aggravation under stress. Excellent and good results (Visick scale) were achieved in 76%. Fair results were achieved in 20%. To date, perforation and other complications have not occurred. Mortality was zero. Our series was an uncontrolled trial, so the results are hardly comparable to other studies. Furthermore, the small number of patients in our study represents a weak point with regard to complications. We conclude that the main advantages of the procedure are its simplicity and practicability. The simple procedure may be the method of choice in elderly patients. Of course, no final decision can be made until a well-designed controlled trial has been carried out. PMID- 3332477 TI - Sonographic evaluation of the portal venous system after elective endoscopic sclerotherapy of esophageal varices. AB - In order to evaluate possible changes in the portal venous system after endoscopic sclerosis of esophageal varices, 25 cirrhotic patients underwent abdominal ultrasonography before the first session of sclerotherapy and after eradication of esophageal varices had been achieved. The caliber of the portal, splenic, and superior mesenteric veins was measured sonographically in each case. Sonographic results were compared statistically before and after sclerotherapy. Neither evidence of significant variations in the caliber of the portal veins nor thrombotic obliteration was seen. These results support the view that sclerotherapy has no significant negative side effects on the portal venous system. PMID- 3332478 TI - Acute colonic pseudo-obstruction (Ogilvie's syndrome). Presentation of 14 of our own cases and analysis of 1027 cases reported in the literature. AB - In addition to the presentation of 14 of our own patients, this study analyzes 1027 cases with acute colonic pseudo-obstruction reported in the literature from 1948 to 1987. Principal associated diseases are cardiopulmonary insufficiencies, postoperative conditions, and systemic disorders. The syndrome is related to a disturbance of colonic autonomic innervation resulting in gross dilatation of the cecum and the right hemicolon. Therapeutic measures include conservative management, colonoscopic decompression, and surgical procedures. The latter have been associated with high morbidity and mortality. Our data support a nonoperative approach to this condition, including conservative measures and colonoscopic decompression as the initial therapy of choice with few complications and high efficacy. PMID- 3332479 TI - Endoscopic management of carcinoma of the esophagus. PMID- 3332480 TI - Water, temperature and life. PMID- 3332481 TI - Temperature and animal cell protein synthesis. AB - A predominant feature of brief heat stress to animal cells is the vigorous but transient activation of a small number of specific genes, previously either silent, or active at low levels. New mRNAs are actively transcribed from these genes and are translated into proteins, known collectively as the heat shock proteins, or hsps. The number of different types of hsp varies considerably in different organisms and cell types but in all cases proteins of approximately 84 and 70 kDa are amongst the most prominent. A dramatic feature that emerges from a study of their genes is that these proteins have been highly conserved during evolution. Gene sequence data reveal specific nucleotide sequences upstream of the transcription start sites that are essential for induction. These are known as 'heat shock elements' and are believed to be the region to which activated 'heat shock transcription factors' bind to facilitate hsp gene transcription. A recent model suggests that transcriptional regulation is based on competition between abnormal intracellular proteins and such a labile regulatory factor. Other experiments suggest such hsp inducers as heat, ethanol, arsenite, or oxygenation after anoxia, may cause protein damage through oxygen-derived free radical action. Although heat shock can cause very considerable changes in transcriptional patterns, effects specifically on translational control are no less dramatic. Different organisms achieve a rapid change in different ways. In Drosophila, heat shock promotes the translation of hsp mRNAs. In yeast there is no mechanism for sequestering pre-existing mRNAs from translation. Instead these mRNAs simply disappear rapidly from the cell. Mammalian cells are different in yet another way. There is neither sequestration of pre-existing mRNAs nor their removal from the cell. Superimposed upon the transient heat induced activation of hsp genes there are now clear indications of developmental regulation. The mechanism for the specific developmental control of hsp expression is not yet known. However, as oncogene products are known to induce hsp synthesis it may be that hsps are involved in eukaryotic growth control. Hypothermia causes loss of protein synthetic activity in cultured animal cells. No specific proteins are however induced and recovery at 37 degrees C is rapid. PMID- 3332482 TI - A temperature-compensated ultradian clock explains temperature-dependent quantal cell cycle times. AB - The effects of sublethal heat pulses on cell division have provided insights into possible molecular mechanisms. Thus Zeuthen's findings of 'set-backs' up to a transition point provides the basis for the idea that the continuous accumulation of a compound needed for cell division spans a major portion of the cell cycle. The accumulating substance is a 'division protein' which forms part of a structure which is unstable until completely assembled at the transition point. Experiments showing phase resetting of mammalian cells by temperature perturbation indicate limit-cycle oscillator control of the cell cycle with a phase-response curve with a repeat interval equal to the period of the clock. As well as providing a method for establishing synchronized cultures these observations have found application in the selective effects of hyperthermia as an antitumour agent. Circadian rhythms display several unique features distinguishing them from other periodic processes. Only recently has it been recognized that some of these characteristics may be properties of ultradian rhythms as well. The probably most striking feature of circadian timekeeping, i.e. independence of ambient temperature, was found for ultradian rhythmicity even at the level of the unicellular organization. Synchronous cultures of some lower eukaryotes were prepared by centrifugal size selection methods. Experiments with asynchronous control cultures substantiated the view that the conditions employed were such as to minimize any perturbative effects: most importantly the organisms were never removed from their culture medium. Whereas the control cultures showed smoothly increasing respiration rates, total RNA, total protein, enzyme activities and enzyme protein (e.g. for cytochrome aa3, ATPase, catalase), in synchronous cultures all these parameters showed oscillatory behaviour. Different periods were observed in different organisms: thus in Acanthamoeba castellanii the period was about 70 min, in Tetrahymena pyriformis strain ST it was about 50 min, in T. pyriformis AII it was 30 min, and in Candida utilis it was about 30 min (all measurements at 30 degrees C). In A. castellanii the periods of both the oscillations in rate of respiration and the total cell protein were hardly affected by the temperature of growth over the range 20 to 30 degrees C. The oscillations show no damping during experiments lasting 12 h: these properties suggest that we are observing temperature-compensated endogenous rhythms which presumably serve a timekeeping function in cells undergoing growth and division.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332483 TI - Cellular heat injury: are membranes involved? AB - Temperature has an all pervasive influence on cellular function. In consequence heat damage may occur at multiple sites. This is only one factor that makes the identification of the primary sites of heat perturbation difficult. It is also likely that cellular heat death is the consequence of a time-dependent accumulation of secondary damage that results from the primary lesion(s). It is important therefore to determine whether observed damage is a primary consequence of heating or a secondary 'knock-on' effect. The case will be considered for a role of cellular membranes as being a cellular site of the primary lesion in heat injury. PMID- 3332484 TI - Hyperthermia effects on the cytoskeleton and on cell morphology. AB - Human erythrocyte ghost membranes undergo five thermal transitions at temperatures between 50 and 75 degrees C. Spontaneous fragmentation of whole cells occurs at 50 degrees C, a transition temperature which has been associated with denaturation of the cytoskeletal protein spectrin. Haemolysis occurs at 65 degrees C and microvesiculation of the resulting ghost membrane is seen at temperatures in excess of 70 degrees C. The cell fragmentation develops through spatially periodic growth of surface waves on the erythrocyte membrane. The interfacial instability associated with the surface wave growth arises from thermal impairment of the stabilizing function of spectrin. Interfacial instability is also associated with the beading pattern which arises when long processes drawn mechanically from erythrocytes are heated. Similar beading of cell processes is a feature of many cytoskeleton-weakening agents acting on nonerythroid cells. The complexities of the cytoskeletons of eucaryotic cells including structure, composition and interaction of cytoskeletal microfilaments, microtubules and intermediate filaments, both with each other and with the cell membrane, are outlined. Attention is drawn to the importance of the function of proteins which interact with the cytoskeletal elements and to the influence of calcium concentration on those proteins. Actin monomers are denatured (and are no longer polymerizable) at temperatures a few degrees above the growth temperature of the cell source of the actins. Actin in the filament form requires much higher denaturation temperatures. This greater thermal lability of actin monomers would be expected to result (because of treadmilling in microfilaments) in a gradual depolymerization of the filaments. Depolymerization of microtubules occurs at temperatures close to the cell growth temperature and may be dependent on a thermal effect on microtubule-associated proteins. The response of spread interphase mammalian cells to temperatures around 43 degrees C includes central retraction of membrane, loss of microvilli, concentration of organelles in a juxtanuclear position, rounding up of the cell, retention of contact with the substratum by processes which are sometimes beaded and blebbing of the cell membrane. The morphological effects of heat are compared here with those of cytochalasin, colcemid and a number of morphology modifying agents. Blebbing of membrane is a fairly general response of cells to stress. Proteins in blebs diffuse as if released from a lateral constraint. Moderate heating has been shown to cause cortical microfilament separation from the plasma membrane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332485 TI - Temperature and macromolecular structure and function. AB - Stability is frequently a knife-edge phenomenon and it is this aspect which is both essential for the effective involvement of macromolecules in the living cell and also provides the basis for the sensitivity of some macromolecular systems to temperature. The response of proteins and nucleic acids is relatively simple at the phenomenological level, with rather sharp 'melting' transitions occurring. Since however the thermodynamic stability of both depends on the cooperation of a variety of non-covalent interactions which are qualitatively well understood but quantitatively difficult to assess, the full understanding and prediction of structural stability still evades us. We shall consider the effects of temperature on the different non-covalent interactions and how far these can account for protein and nucleic acid denaturation at elevated temperatures and also the cold inactivation of proteins. The latter has recently been shown to involve unsuspected complications in terms of protein conformational change. The increased stability of proteins and nucleic acids from thermophiles will be discussed. Stability is important not only in native folded proteins but also with respect to intermediate structures which occur during the folding of the newly synthesized polypeptide chain into the native, active protein. Through studies of protein folding the molecular basis of the phenomenon of temperature sensitive synthesis has been revealed. Given a stable molecular structure, its function will frequently be subject to variation with temperature. The deceptively simple temperature dependence of enzyme activity will involve the non covalent interactions considered above for interaction between enzyme and substrate and for stability of the transition state complex. This complexity again makes the temperature dependence difficult to interpret. Further, the fact that proteins are dynamic structures is becoming recognized as an important feature factor in determining function. A balance has to be struck between on the one hand dynamic mobility which is essential for catalytic activity and on the other thermodynamic stability which holds the molecule in a potentially functional conformation under the given conditions of temperature and pressure. Readjustment of thermostability stability, as in thermophiles (or vice versa?), must also involve readjustment of dynamic mobility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332486 TI - Sensitivity of tumour cells to heat and ways of modifying the response. AB - In our view, the initial effect of hyperthermia on cells is the disorganization of the membrane lipid. Such disorganization alters the membrane's biophysical properties leading to passive changes in transmembrane permeability, shifts in surface charge, and altered stereoorganization of macromolecules associated with the membrane. For example, the passive permeability changes could account for the observed increase in the association of non-histone proteins to chromatin. Surface charge changes resulting from relative changes in the phospholipids could shift the concentration and types of membrane-bound proteins. Such events could initiate hyperthermic cell death. Membranes of tumour cells are characterized by elevated cholesterol. Such differences in cholesterol concentration with their attendant shift of biophysical characteristics could explain the variation in heat sensitivity between cell lines and within the cell cycle. Further support for lipids being the initial target comes from our studies demonstrating enhanced thermosensitivity when anaesthetics are present. Thermosensitivity of solid tumours is not further influenced by lidocaine in host animals fed diets enriched in linoleic acid, a diet which markedly modifies fatty acid, phospholipid patterns and cholesterol concentration of cellular membranes. One should recognize that global measures of change, such as the ratio of unsaturated to saturated fatty acids, in unsaturated fatty acid index, or percentage of unsaturated fatty acids, may not accurately reflect changes in fatty acid patterns which are related to changes in thermosensitivity. For example, we now recognize that double bond location with respect to the headgroup must be considered as well as the relative content of unsaturated fatty acids in the membrane. Further studies bearing on the role of diet and anaesthetics on cell killing and on metastatic spread are needed. An increased understanding of the relationship of membrane biophysics and biochemistry correlated with how cells respond to heat could aid in elucidating the mechanisms of cell death. Such knowledge could provide a more rational basis for cancer therapy. The association between pyrexia and tumour regression was noted as early as 1866 by Busch who observed neoplasm remission in patients afflicted with severe erysipelas (Busch, 1866). Over the past 80 years clinicians have on occasion treated tumours by heat alone or, more recently, in combination with radiotherapy (Dickson, 1979; Jensen, 1903).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332488 TI - Cold tolerance in mammalian cells. AB - As whole organisms, most mammals have a poor tolerance for hypothermia. But their cells may have a capacity for a far wider cold tolerance, which may be expressed in peripheral tissues, sporadically in core tissue and in cultured cells. Against this background the cold resistance of cells of deep hibernators may be seen as the extreme of a continuum and is complicated by the consideration that the voluntary hypothermia of hibernation is probably in most cases a metabolic adaptation to forestall starvation. Similarly, cold resistance of peripheral tissues may in diving animals be confounded by the need to be adapted to hypoxia as well. Hence, attempts to analyse cold resistance by comparisons of absolute rates of arbitrarily chosen reactions may be misleading. A more useful approach is analysis of maintenance of balance: balance between ATP synthesis and utilization, balance between macromolecule synthesis and degradation and balance between pumps and leaks. Cation pumps and leaks constitute a major component of energy utilization and are central to other cell functions, even during minimal metabolism. Hence, the maintenance of ion gradients is a central issue in understanding adaptation not only to hypothermia but also to starvation and hypothermia. Of the three hypometabolic states, hypothermia has been best studied in this regard. In most cases, passive permeability is more reduced at low temperature in cold-tolerant cells than in cold-sensitive ones. In some cases there is also a difference in Na-K pump activity and perhaps in ATP dependent Ca pump activity. Pump activities and probably the maintenance of minimal leak require ongoing metabolism. The question of whether, in cold-sensitive cells, energy supplies are adequate at low temperature was once the focus of this field, but has been ignored for a decade without having been fully resolved. There are many instances of less temperature sensitivity of specific metabolic activities (mitochondrial respiration, etc.) in hibernators than in non-hibernators, without any verification of whether this is essential for survival at low body temperature. Certainly, robust pumping has been found in some failing cold sensitive cells at low temperature, suggesting no shortage of ATP in these cases, but in other cases the issue may be a more complex one than just that of ATP availability.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332487 TI - Thermotolerance and the heat shock proteins. AB - Mammalian cells can dramatically increase their tolerance to thermal damage after prior heat conditioning. The thermal history, the heat fractionation interval and the recovery conditions, all modify significantly the degree of thermotolerance exhibited. Several lines of evidence have suggested that perhaps that shock proteins (hsps) provide the protective mechanism. For example by following the synthesis and degradation of heat shock proteins during development and decay of thermotolerance, strong circumstantial evidence has been obtained in certain cases that hsps are involved in the acquisition, maintenance and decay of thermotolerance. The levels of certain heat shock proteins, particularly the class at 68-70 kDa, can also correlate with thermotolerance. On the other hand these correlations do not always hold. Moreover cycloheximide treatment during the heat shock does not appear to block the development of thermotolerance. In addition depletion of medium Ca2+ which also inhibits hsp induction can produce thermotolerance. However it should be emphasized that whilst hsp synthesis is elevated after heat shock, it is clear that there are low level of hsps, always present in unheated cells, which may be sufficient to confer tolerance. Other data now show that thermotolerance measured in terms of cells survival is closely parallel by thermal resistance of total protein synthesis. Moreover it is possible to demonstrate the development of thermotolerance in the total protein synthetic activity of Hela cells, either held continuously at 42 degrees C or treated briefly at 45 degrees C and returned to normal growth temperature. This development of tolerance in the total protein synthetic activity is nonetheless reduced by actinomycin D and a role for the nucleolus is suggested. The properties of hsps that might be of significance in the generation of thermotolerance are examined. For example there appears to be a specific role of hsp 70 in aiding repair of heat damaged nucleoli. Another heat shock protein appears to be ubiquitin which is likely to have a role in the degradation of the abnormal proteins which are postulated to be involved in the transcriptional activation of the hsp genes themselves. PMID- 3332489 TI - Cold shock injury in animal cells. AB - Cold shock injury (damage to cell structure and function arising from a sudden reduction in temperature) was for many years considered a phenomenon peculiar to certain cell-types. Only in recent years has it become apparent that widely different cell-types manifest cold shock injury. Thus, cold shock appears to be a more general phenomenon, differences between cell-types being quantitative (in the rate of cooling and temperature range at which injury is sustained) rather than qualitative. Loss of particular cell functions depends on cell-type, but reflects the underlying structural and biochemical damage which has been inflicted by rapid cooling. In particular, membranes lose their selective permeability with the result that many cellular components are released including lipids, proteins and ions. Additionally, sodium and calcium gain access to the interior of the cell. Consequent upon this initial disruption, metabolic activities are diminished and further secondary changes ensue. The possible mechanisms of cold shock injury include membrane thermo-tropism and protein denaturation. Susceptibility to cold shock is influenced by membrane composition, and much experimental evidence points to particular involvement of membrane lipids. One hypothesis implicates lipid phase changes in a cooling rate dependent loss of membrane integrity. Other recent hypotheses invoke biophysical concepts and cytoarchitectural features as considerations in a better understanding of cold shock. PMID- 3332490 TI - Storage of cells and tissues at hypothermia for clinical use. AB - The ability of cells and tissues to withstand periods of removal from, or severe changes in, their normal environment is a necessary consequence of many surgical and medical therapies, particularly in the growing area of transplantation. The sequence of changes in mammalian cells during ischaemia is discussed. Following from this, the ability of hypothermia to slow all cell metabolic processes is described, and the concept is introduced that hypothermia itself eventually causes cell damage. Current knowledge on hypothermic damage is outlined, and the biological basis for therapeutic measures to minimize this damage is described. Finally, brief descriptions are given for hypothermic storage regimes in use clinically at present. PMID- 3332491 TI - The effects of temperature on biological membranes and their models. AB - The physical effects of temperature on biological membranes are reviewed. Our current understanding of membrane structure is based on a model in which proteins are inserted in or are attached to a lipid bilayer structure. The lipid composition varies between cell types. Phospholipid bilayers undergo phase transitions at temperatures which are dependent on chain length and the structure of the headgroup. These factors also affect the miscibility of phospholipid types. Cholesterol orders the phospholipid chains above their phase transition temperature but disorders them below this temperature. Cerebrosides, which are important constituents of the myelin membrane, form metastable states under certain conditions. The activities of membrane-bound enzymes may be affected by the physical state of the lipid bilayer which, in turn, is affected by temperature. The interactions between the lipid and protein components of membranes have been investigated by a variety of techniques. PMID- 3332492 TI - Mechanisms of freezing damage. AB - Freezing of aqueous systems involves numerous simultaneous changes but this review concentrates on direct effects of the formation of ice and the consequent concentration of solutes in the remaining liquid phase. It is generally believed that cell injury at low cooling rates is principally due to the concentration of both intracellular and extracellular electrolytes and that cryoprotectants act by reducing this build-up. New experimental data are presented to support this explanation; we find that the extent of damage to human red blood cells during freezing in solutions of sodium chloride/glycerol/water can be quantitatively accounted for by the increase in solute concentration. However, we also show that a given degree of damage occurs at lower concentrations of solute in the presence of higher concentrations of glycerol; it appears that glycerol contributes an element of damage itself. Recently published studies from Mazur's laboratory have suggested that the dominant damaging factor at low cooling rates is actually the reduction of the quantity of unfrozen water rather than the corresponding increase in salt concentration that accompanies freezing. These data are re evaluated, and it is argued that the experimental results could equally well be explained by a susceptibility of cells to shrinkage and re-expansion as the concentration of external impermeant solutes first increases during freezing and then decreases during thawing. It is concluded that external ice probably has no directly damaging effect upon dilute suspensions of cells. However, it is also argued that ice is directly damaging whenever it forms intracellularly, and also when it forms extracellularly in densely packed cell suspensions. In the latter case the damage is probably due to recrystallization of the ice masses during thawing. Extracellular ice also has a directly damaging effect when tissues and organs are frozen. The difficulties of designing experimental methods that will yield unequivocal results is emphasized, and consequently the above conclusions must be regarded as tentative at the present time. PMID- 3332493 TI - Cryopreservation of animal cells. AB - A wide range of cells of biological, medical and agricultural importance can be cryopreserved at -196 degrees C for many years in a stable state. The survival after freezing and thawing of different types of cell varies markedly, and depends on the ability of the cells to withstand a variety of stresses imposed by the physical and physico-chemical changes occurring in the bathing medium during cooling to and warming from the storage temperature. In most instances, cells will survive freezing only when a cryoprotectant (an additive such as glycerol or dimethyl sulphoxide that can protect cells against freezing injury) is included in the bathing medium: moreover, survival is dependent on the rates at which cells are cooled and warmed. Each cell type has an optimum cooling rate at which survival is maximal. This optimum cooling rate is determined to a large extent by the water permeability of the cell; but it is also influenced by the presence of cyroprotectants, and the warming rate. Therefore, when devising a method of cryopreservation for a particular cell type, the most important variables are the rates of cooling and warming, and the type and concentration of cryoprotectant. In general, as the concentration of cryoprotectant is increased, cell survival improves cryoprotectants can have detrimental toxic and osmotic effects on cells. Therefore, the way in which cryoprotectants are added to the bathing medium before freezing and, in particular, the procedure used to return the cells to a medium without cryoprotectants after thawing, can be crucial to the survival of the cells. Vitrification could be a way to avoid the mechanisms of injury associated with the formation of ice. When an aqueous solution contains a sufficiently high concentration of solute (e.g. greater than 40% w/w of the cyroprotectant propane-1,2-diol), the large increase in viscosity that occurs during cooling inhibits ice formation, and the solution eventually becomes an amorphous, glassy solid. There is no formation of a crystalline solid, nor is there a progressive rise in solute concentration, both of which occur as a result of ice formation during cooling. Vitrification could, therefore, prove to be a useful alternative method of cryopreservation, particularly for organized tissues and organs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332494 TI - Mechanisms of cryoprotectant action. PMID- 3332495 TI - Biochemical and functional aspects of recovery of mammalian systems from deep sub zero temperatures. AB - The viability of isolated mammalian systems is, apart from possible morphological changes, essentially conditioned by the biochemical modifications from normal physiological conditions to an artificial environment where blood supply is interrupted leading to ischaemia and where the temperature is lowered. In order to survive freezing and thawing, mammalian systems have to be protected by cryoprotectants, which apart from some inherent toxicity, may also interact with vital metabolic mechanisms (Conover, 1969, 1975: Fahy, 1986: Fahy et al. 1984: Jacobs & Herschler, 1986: Karow, 1982: Penninckx et al. 198 3: Polge et al. 1949: Rowe et al. 1980: Schlafer, 1981: Taylor & Pignat, 1982). Cellular volume changes as a result of modifications in extra- a and intracellular osmolality occurring during freezing and thawing prove particularly detrimental to the normal functioning of the cellular membranes (Crowe et al. 1983: Farrant, 1980: Farrant et al. 1977b: Karow, 198 2: Mazur & Rigopoulos, 1983: Meryman, 1970: Meryman et al. 1977: Nei, 19 76: Santarius & Giersch, 1983). Furthermore intracellular ice formation enhances structural and metabolic injury to subcellular particles(Farrant et al. 1977a: Fink, 1986: Fishb ein & Griffin, 1976: Fujikawa, 1981: Fuller & De Loecker, 1985: Lazarus et al. 1982: Malinin, 1972: Mazur, 1984: Pavlock et al. 1984:Penninckx et al. 1984: Persidsky & Ellet, 1971: Rubinacci et al. 1986: Shikama, 1965: Steponkus & Wiest, 1979: Strauss & Ingenito, 1980: Takehara & Rowe, 1971: Tamiya et al. 1985). Even with the protection of structural integrity, the preservation of energy production and the maintenance of the specific intracellular medium are essential to secure viability (Pegg, 1981). PMID- 3332496 TI - Temperature effects on different organization levels in animals. AB - One of the central concepts in present biology is the recognition of different organization levels and their hierarchical array. Complex multicellular animals are constituted of organ systems, the organs of cells, the cells of organelles, membranes, and molecules. The primary effects of many environmental factors (e.g. light, concentrations of ions and molecules) can be delimited mainly to one level. Temperature, being the macroscopic physical measure of the random motion of smallest material particles, affects directly the animal life at all organization levels. The special physical nature of temperature means also, that during the history of life, organisms have always been subjected to temperature variations. Many different ways to evade the pervasive effects of temperature have been evolved during the course of evolution. The study of the temperature relations of organisms can therefore give models for other branches of environmental biology. The temperature limits and relations of an animal cannot be explained by the temperature relations and limits of its cells without taking into account such interactions between different types of cells, which are found only through the study of the organs. Also, the temperature limits and relations of animal cells cannot be explained just through the study of the constituent molecules. The possible interactions of the molecules (e.g. lipids and proteins in a cell membrane) are so manifold and complex that in order to ascertain the relative importance of them in the temperature relations of the cells we must rely in part on studies done on organelles (e.g. on the plasma membrane). The study of the thermal biology of animal cells thus exemplifies the situation often found in biology: the attainment of a reductive explanation is not always a one way deduction, but it may involve modifications of the lower level concepts according to the knowledge derivable only from studies of the higher level systems. PMID- 3332497 TI - Temperature acclimation and metabolism in ectotherms with particular reference to teleost fish. AB - As body temperature decreases, changes in the physical chemistry of the cell produce a reduction in metabolic activity. In temperate fish, cold water temperatures either lead to dormancy or else trigger a range of homeostatic responses which serve to offset the passive effects of reduced temperature. Compensatory adjustments to temperature occur with time courses ranging from less than a second to more than a month. Although swimming performance may increase with cold-acclimation, active metabolic rate remains significantly below that for warm-acclimated fish. Compensatory and dormancy responses are not mutually exclusive and sometimes occur in the same species depending on the temperature. Cold-acclimation results in significant increases in the density of mitochondria and capillaries in skeletal muscle. This serves to reduce diffusion distances and increase the capacity for aerobic ATP production relative to fish acutely exposed to low temperature. There is evidence that cold acclimation has differential effects on the synthesis and degradation rates of mitochondrial proteins leading to a net increase in their concentration. In contrast, the activities of enzymes associated with glycolysis and phosphocreatine hydrolysis show no consistent changes with thermal acclimation suggesting that flux through these pathways is modulated by factors other than enzyme concentration. Higher mitochondrial densities have also been reported for the liver, brain and gill tissue of cold compared with warm acclimated fish. In spite of their increased concentration, the activities of aerobic enzymes remain much lower at cold than warm temperatures. Acclimation temperature affects hepatosomatic index, the concentration of energy reserves, and the relative importance of glucose and fatty acid catabolism in liver. The fraction of glucose oxidized by the hexose monophosphate shunt (HMPS) pathway also increases with cold acclimation in some species. It is likely that many of the changes in liver metabolism with temperature acclimation reflect associated changes in feeding behaviour and/or diet, and other energetic demands (e.g. gametogenesis). Possible mechanisms underlying alterations in pathway utilization with temperature acclimation are discussed. They include changes in factors influencing enzyme structure and activity (e.g. pH, substrate/modulator concentrations, phosphorylation state, membrane composition), and effects of temperature on gene expression. PMID- 3332498 TI - Adaptive responses of animal cell membranes to temperature. PMID- 3332499 TI - Real-time ultrasonic diagnosis of ovarian tumors. PMID- 3332500 TI - Arboviral causes of non-specific fever and myalgia in a fever hospital patient population in Cairo, Egypt. AB - Fever and myalgia are non-specific clinical manifestations of illness which commonly occur in patients with arboviral disease. In Egypt, such illness is often mis-diagnosed as "influenza". To determine arboviral aetiology in patients admitted with fever and myalgia, acute and convalescent sera samples were obtained from 55 patients admitted with these clinical manifestations to the Imbaba Fever Hospital, Giza, Egypt, during October and November 1984. Based on viral isolation, and a comparison of acute and convalescent sera, 4 patients (7%) had acute arboviral infections. Haemagglutination inhibition and indirect immunofluorescence tests showed that one had West Nile virus (WNV) infection, 2 had sandfly fever virus-Naples (SFN), and 1 had sandfly fever virus-Sicilian (SFS) infection. SFN was isolated from the acute serum sample of 1 of the 2 patients with SFN infection. PMID- 3332501 TI - Use of phenolic glycolipid 1 for serodiagnosis of leprosy in a high prevalence village in Papua New Guinea. AB - This study reports on the usefulness of an IgM phenolic glycolipid 1 (PGL-1) ELISA for serodiagnosis of leprosy in the first year of a prospective longitudinal community survey in a high (8.8%) prevalence village in Papua New Guinea. The IgM PGL-1 ELISA had limited value as a screening method for detection of new cases. Many normal persons, particularly children, had elevated IgM anti PGL-1 antibodies, presumably a consequence of early subclinical infection. PMID- 3332502 TI - The effect of substance(s) associated with malarial parasites on C3b inactivator. AB - The effects of a substance or substances associated with malarial parasites on the inhibitory role of C3b inactivator in immune adherence were investigated. The test system involved adherence of immune complexes of complement-bearing sheep erythrocytes and rabbit antibody, using human group O erythrocytes and human renal glomerular tissues as indicators. Malarial antigen and other soluble by products of the malarial parasites, presumably present in spent culture medium, did not interfere with the inhibitory role of C3b inactivator. However, malarial pigment, both crude and purified, enhanced immune adherence in the presence of C3b inactivator. It is suggested that malarial pigment, by inhibiting the action of C3b inactivator, may play a significant role in the immunopathogenesis of renal lesions associated with malarial infections. PMID- 3332503 TI - Characterization of Plasmodium falciparum cloned lines with respect to gametocyte production in vitro, infectivity to Anopheles mosquitoes, and transmission to Aotus monkeys. AB - The production of gametocytes in vitro and their subsequent infectivity to mosquitoes by 3 cloned lines of Plasmodium falciparum were studied. 2 of the cloned lines, Honduras I-clone B3 and Indochina III-clone W2, produced mature gametocytes (stage V) that were infective to Anopheles mosquitoes. The third clone, Sierra Leone I-clone D6, produced gametocytes, the majority of which did not develop beyond stage III. Fully mature gametocytes of Sierra Leone I-clone D6 were not infective to mosquitoes. Sporozoites collected from An. freeborni infected with Honduras I-clone B3 were used in transmission studies. Two of three Aotus monkeys were infected after prepatent periods of 19 and 20 d, respectively. This study supports previous reports that cloned lines of P. falciparum contain the full genetic capacity to produce morphologically mature gametocytes. The transmission to Aotus monkeys has also conclusively established that biologically competent gametocytes of both sexes are produced by clones. PMID- 3332504 TI - Diagnosis of tertian malaria by enzyme-linked immunosorbent assay. AB - A method of ELISA diagnosis of tertian malaria based on detecting Plasmodium vivax antigen in red blood cells (RBC) was developed, using 0.16 ml of packed, washed, and sonicated RBC. 68 blood samples from tertian malaria cases were examined; 67 (98.5%) were positive. 104 normal persons were all negative by this test. The lowest parasite number detected was 3 parasites/10(5) RBC on a thin film, or 1-2 parasites per thick film of usual size. PMID- 3332505 TI - Sera from Cameroon recognize proteins of Plasmodium falciparum isolates from geographically diverse areas of the world. AB - Immunological reactions of clinically-defined sera collected from 176 children and adults (3 to 63 years of age) living in malaria endemic regions of Cameroon were evaluated by ELISA, growth inhibition studies and immunoprecipitation assays using different parasite isolates from geographically diverse areas. The proportions of sera positive by ELISA and with positive growth inhibitory activity tended to increase with increased age. SDS-PAGE analyses of immunoprecipitates using [35S]methionine labelled parasite polypeptides revealed that a wide range of proteins was recognized by the sera. There were many similarities in the patterns of antigens immunoprecipitated in the different isolates, particularly when immune sera were used. Variability in response was more evident in sera collected from children. These findings suggest that strains may share components which generate protective immunity. PMID- 3332506 TI - The use of immunofluorescence to evaluate the efficacy of malarial chemoprophylaxis. AB - 338 subjects occupationally exposed to high levels of malaria transmission were randomly assigned to three groups. Group A received one tablet of mefloquine (250 mg) and one tablet of sulfadoxine-pyrimethamine once a week, group B received two tablets of sulfadoxine-pyrimethamine once a week and group C received one tablet of sulfadoxine-pyrimethamine (each containing sulfadoxine 500 mg and pyrimethamine 25 mg) twice a week. Blood films for malaria parasites and filter paper strips for serological study were taken before and at 5 and 12 months after the chemoprophylaxis. The advantages and inherent limitation of the slide positivity rate and the usefulness of geometric mean reciprocal titre for the assessment of the efficacy of the chemoprophylaxis were discussed. PMID- 3332507 TI - Inhibitory effect of beta zero-thalassaemia/haemoglobin E erythrocytes on Plasmodium falciparum growth in vitro. AB - The growth of Plasmodium falciparum in erythrocytes from individuals with beta zero-thalassaemia or haemoglobin (Hb) E, or both, was assessed in vitro. A significant inhibitory effect on the growth of the parasite was found only with erythrocytes from individuals doubly heterozygous for beta zeros-thalassaemia and HbE. The inhibitory effect was particularly marked with erythrocytes from splenectomized beta zeros-thalassaemia/HbE patients. The protective effect was related to HbF, Hb levels and shape abnormalities of the variant erythrocytes. PMID- 3332508 TI - The complete development in vitro of the vertebrate phase of the mammalian malarial parasite Plasmodium berghei. AB - All three 'vertebrate' stages of the rodent malarial parasite Plasmodium berghei berghei were grown in vitro in the absence of the vertebrate host. The parasite was introduced into culture from infected mosquitoes and 2 in vitro culture methods were used sequentially to complete the 'vertebrate' phases of development in hepatoma and erythrocyte host cells. The resultant blood infection produced mature schizonts and male and female gametocytes. The protocol, which is now being extended to the human pathogen P. falciparum, may assist future studies on this important group of parasites. PMID- 3332509 TI - Double-blind trial to find dose range using a fixed combination of mefloquine, sulfadoxine and pyrimethamine in falciparum malaria: a field study on adults in Burma. AB - In a field study conducted in Burma, 60 semi-immune adults were randomly assigned to 2 treatment groups. The first (mean parasite count, 12717/mm3) received a single dose of a fixed combination of 500 mg mefloquine base, 1000 mg sulfadoxine and 50 mg pyrimethamine (2 tablets of 'Fansimef') plus 1 tablet placebo. The second group (mean parasite count, 11 863/mm3) were given 3 tablets of the same medication. The study was double-blind. Parasite count was checked daily for the first week and weekly for a further 3 weeks. Average times for parasite clearance were 1.47 d in patients receiving 2 tablets, and 1.87 d in those given 3 tablets. Asexual parasites reappeared on day 28 in one patient in each group, although they had been free of parasites during the previous 4 weeks; this could be due to reinfection. The drugs were generally well tolerated, though mild and transient giddiness was seen in 80% of patients in the first group and 96% in the second. Nausea was reported by 33% and 43% of patients respectively. No vomiting occurred in the first group but 8 patients vomited in the second (P less than 0.01). In conclusion it seems possible to treat falciparum malaria in semi-immune adults, weighing less than 60 kg, with a single dose of 500 mg mefloquine base, 1000 mg sulfadoxine and 50 mg pyrimethamine (2 tablets), instead of the higher dose (3 tablets) currently recommended. This reduces treatment cost and improves tolerance of the drugs. PMID- 3332510 TI - Sensitivity of malaria parasites to artemether (qinghaosu derivative) depends on host cell age. PMID- 3332512 TI - [Lessening pain by uncommon methods]. PMID- 3332511 TI - Morphological changes and serological reactions in cultured Leishmania donovani promastigotes. AB - Promastigotes of Leishmania donovani cultured in liquid media gradually changed from a majority of elongated forms through a predominance of intermediate spindle shaped parasites to a majority of round forms, often aflagellate. Quantitative and qualitative differences among these subpopulations, separated on Percoll gradients, could be demonstrated when they were run on SDS-PAGE gels and stained from proteins or carbohydrates. When cultures containing a majority of one or other form were used as antigenic substrate in serological tests (ELISA and immunofluorescence) the older, round forms were more highly reactive with patients' sera. These forms may represent different phases of the parasite, related to function, and the density variations would provide a convenient method to separate them. PMID- 3332513 TI - Roots, Steam Engines, Thermodynamics, and the Cornish Giant. PMID- 3332514 TI - Uncommon illness from common infections. AB - Individual common infectious agents such as EBV, CMV and HBV have well characterized relationships to a variety of acute and chronic disease states; the host and/or environment variables underlying this clinical heterogeneity are not known. Given the high frequency of these viral infections in the general population, there should be a cautious interpretation of antiviral serological data. PMID- 3332515 TI - Interactions between surface molecules and the cytoskeleton in the lymphocyte. PMID- 3332516 TI - Immunotherapy of infectious diseases: past, present and future. PMID- 3332517 TI - Meta-analysis in clinical medicine. PMID- 3332518 TI - The Jeremiah Metzger lecture. Current status of human gene therapy. PMID- 3332520 TI - Ancient magic in modern medicine. PMID- 3332519 TI - Some determinants of low bone mass and fracture among the elderly. PMID- 3332521 TI - The role of grapefruit pectin in health and disease. PMID- 3332522 TI - Obstructive sleep apnea: therapeutic compliance. PMID- 3332524 TI - The need for imaging in acute myocardial infarction. PMID- 3332525 TI - The thirteenth International Conference on Yeast Genetics and Molecular Biology. Banff, Alberta, Canada, 31 August-5 September 1986. Book of Abstracts. PMID- 3332523 TI - The uptake of fatty acids by the liver. PMID- 3332526 TI - [The value of echography in Crohn's disease]. PMID- 3332527 TI - Entero-cutaneous fistulas and Crohn's disease. PMID- 3332528 TI - Crohn's colitis, dysplasia and cancer. PMID- 3332529 TI - The insulin test after highly selective vagotomy. Prognostic value in a series of 73 patients followed for 4-10 years. PMID- 3332530 TI - [Campylobacter pylori gastritis. Comparison of various diagnostic methods]. PMID- 3332531 TI - Autonomic nervous system regulation of murine immune responses as assessed by local surgical sympathetic and parasympathetic denervation. AB - The effect of local sympathetic denervation on immune responses of submaxillary lymph nodes (SmLN) of mice was examined in animals subjected to unilateral superior cervical ganglionectomy (SCGx). Norepinephrine (NE) content in ipsilateral SmLN decreased by 90% 7-20 days after SCGx, while bilateral SCGx resulted in a 91% decrease of SmLN NE content. SmLN of mice subjected to unilateral SCGx exhibited greater plaque-forming cell (PFC) response than the innervated contralateral SmLN, when challenged i.d. or i.p. with sheep red blood cells (SRBC) 10-20 days after surgery. In mice challenged with SRBC at an early phase of sympathetic nerve paralysis (i.e., 2 h after SCGx), PFC response was already increased in the ipsilateral SmLN whereas during the anterograde degeneration of nerve endings (6-24 h after SCGx) an impending depression of PFC number was observed. Contact hypersensitivity and allogeneic delayed-type reactions were also enhanced in the ear ipsilateral to SCGx. Primed SmLN cells of nodes located ipsilaterally to SCGx, when injected to (BALB/c x C57BL/6) F1, resulted in significantly higher spleen index than similarly treated, contralateral SmLN. In contrast, mitogenic stimulation under various experimental protocols failed to reveal significant differences between proliferation of cell populations obtained from ipsilateral and contralateral SmLN of unilaterally SCGx mice. SmLN of mice parasympathetically decentralized by unilateral sections of the chorda tympani-lingual nerve trunk showed lower PFC response than the innervated contralateral SmLN, when challenged with SRBC 8-28 days after surgery. These results suggest a regulatory function of the autonomic nervous system in immune reaction. PMID- 3332533 TI - Attitude assessment for family practice research. AB - One of the methods used often in family medicine research is the measurement of attitudes. This article reviews the options for measuring attitudes and explains the qualities attitude instruments must possess to be effective as research tools. Observations, interviews, surveys, standardized scales and self constructed scales are reviewed as strategies for measuring attitudes. The most common scaling techniques for attitude measurement are also reviewed including: Likert scales, Semantic Differentials, rating scales, and Q-sorts. Methods for ensuring reliability and validity of attitude measurements are also reviewed. Examples of the techniques described are drawn from the family medicine literature to provide readers with references to techniques for use in research. References are also cited for technical guidance in developing the techniques described. PMID- 3332532 TI - [Nickel chloride and alloxan. I. Determination of glucose, insulin and superoxide dismutase in blood and pancreas of rats]. AB - Copper-zinc superoxide-dismutase (SOD-E.C. 1.15.1.1.) is present in high concentration in the beta-cells of pancreatic islets, and its specific activity correlates with maintenance of beta-cell function. In this paper the authors studied the effect of nickel chloride (s.c.) on alloxan toxicity. It was found that alloxan (100 mg x kg-1) inhibited insulin release of rats islets and thus, induced hyperglycemic response. The activity of erythrocytes and pancreatic SOD enzymes was partially inhibited upon alloxan treatment. It was found that nickel chloride (s.c. 10 mg x kg-1) produced stimulation of insulin release in rats treated by subcutaneous (s.c.) alloxan injection. The potential of NiCl2 to prevent alloxan induced diabetes was shown by the observed SOD specific activity increase in rats. In conclusion, our experiments show that nickel chloride prevented alloxan induced toxicity in rats. PMID- 3332534 TI - Polycystic ovaries and polycystic ovary syndrome. PMID- 3332535 TI - Is there a place for androgens in gynecological disorders? PMID- 3332536 TI - In situ hybridization identifies renin mRNA in the rat corpus luteum. AB - All components of the renin-angiotensin system (RAS), including angiotensinogen messenger RNA (mRNA), renin-like activity (RLA), renin mRNA, angiotensin II (A II) immunoreactivity and angiotensin converting enzyme, have been found in the whole rat ovary and A II receptors have recently been localized to ovarian follicles. Our study was designed to test further which part of the ovary can produce renin. Renin mRNA was detected in the gonadotropin-stimulated rat's corpus luteum using in situ hybridization histochemistry techniques. No positive signal was detected in theca or granulosa cells. These results indicate ovarian renin gene expression in rat luteal cells, where the renin molecule is probably produced, and support our concept of an intrinsic ovarian RAS. PMID- 3332538 TI - Significance of hormonal changes in migraine and cluster headache. PMID- 3332537 TI - Modulation of prolactin responses to gonadotropin releasing hormone by acute testosterone infusions in normal women. AB - The administration of gonadotropin releasing hormone (GnRH) has been shown to stimulate prolactin (PRL), suggesting its role as an inducer of PRL release. This study addresses whether testosterone may modulate the release of PRL with GnRH during the early follicular phase when this stimulatory effect is not usually observed. Chromatographically pure testosterone was administered intravenously to 13 women in 2 doses (100 micrograms and 1000 micrograms) over a 6-hour period. GnRH (100 micrograms) was administered as a bolus 2 hours before and 4 hours after beginning testosterone. In addition, 3 women received testosterone twice, 3 months apart, with testolactone pretreatment on the second occasion. Serum testosterone rose in all patients and achieved maximum steady-state levels by 120 minutes. Serum estradiol (E2) was increased in subjects receiving the larger dose of testosterone but was unchanged with the lower dose and with the addition of testolactone. PRL did not increase significantly after GnRH before testosterone infusion but showed a significant increase after testosterone as well as after testosterone with testolactone. This effect did not appear to be dose-related. PMID- 3332539 TI - Menstrual migraine: a possible pathogenic implication of platelet function. AB - It has been suggested that migraine is a blood disorder caused by a primary abnormality of platelet behaviour. We have studied in different phases of the cycle of 11 healthy normal women and 13 patients suffering from menstrual migraine: 1. The platelet aggregation induced in vitro by ADP, collagen and ristocetin; 2. The platelet sensitivity to prostacyclin (PSP); 3. The platelet content of 5-hydroxytryptimine (5-HT); 4. The possible correlation between these parameters and the plasma concentration of progesterone. The results demonstrate that in patients with menstrual migraine the platelet response to various aggregating agents is not modified compared to the controls, whereas there is a different response of the PSP to the modulating effect of plasma progesterone. Moreover, in the same patients the platelets have an increased capability of accumulating 5-HT during the perimenstrual phase of the cycle. This suggests that platelet dysfunction may play a role in the pathogenesis of menstrual migraine. PMID- 3332540 TI - Jewish ethical perspectives on human reproduction. PMID- 3332542 TI - Alterations in gastric acid secretion following hepatic vagotomy at a stage of development in rats. AB - The relation of gastric acid secretion to the hepatic vagal section was examined in consideration of developmental stages of a rat. Acid outputs in rats deprived of food for 22 hr before the experiment were estimated with or without insulin. The animals were classified into five groups according to their body weights at the experiments (50, 100, 200, 300 and 400 g). Hepatic vagotomy was effective in decreasing acid output in all of the groups treated with food deprivation and insulin, and it was found that there was a close relationship between the output and glucose concentration in the portal blood. In rats treated only with food deprivation, hepatic vagotomy produced different effects for the five groups; the vagotomy failed to cause acid response when the rats weighed about 300 and 400 g, while in the animals weighing about 50, 100 and 200 g acid outputs were reduced following the vagotomy. It was noted that the sensitivity to hypoglycemia in the acid output was greater in the young rats than the older ones. Results suggest that function of the hepatic vagal nerve may be prominent in modulating acid secretion in an earlier stage of development when the animals are most sensitive to hypoglycemia. PMID- 3332541 TI - Thrombin is a potent mitogen for rat astroblasts but not for oligodendroblasts and neuroblasts in primary culture. AB - Astroblasts from brain of newborn rat can survive and even proliferate to some extent in a chemically defined medium containing no other growth factor than insulin, providing they are grown first in the presence of fetal calf serum for at least 4 days (Weibel et al., 1984, Int. J. devl Neurosci. 2, 355-366). We found that thrombin is a potent mitogen for these cells, in vitro. The mitogenic activity of thrombin for astroblasts can be compared to that of the astroglial growth factor on astroblasts. However, in contrast to the bFGF, thrombin does not modify significantly the morphology of the cells and their synthesis of glutamine synthetase, an astroglial marker in rat brain. Some other proteases are also able to stimulate the proliferation of astroblasts, but to a lesser extent than thrombin. Thrombin does not stimulate the proliferation of oligodendroblasts from newborn rat and of neuroblasts from 13-day-old rat embryo. These results suggest that in the central nervous system thrombin might play a role in the induction of astrocyte proliferation after brain injury. PMID- 3332543 TI - Current aspects of the development of the blood-brain barrier. AB - Results of earlier studies clearly indicated that, during development, a number of enzymes are sequentially expressed in the brain endothelial cells correlating in time with the maturation of brain tissue. More recent data suggested that differentiation of endothelium in the intraparenchymal cerebral microvessels into one with blood-brain barrier characteristics seems to be induced by astrocytes at a specific time of embryonic development. Details of the above-mentioned and other important aspects of the development of the blood-brain barrier will be discussed in the present mini review. PMID- 3332544 TI - Expression of human interferon alpha H, an interferon with two potential asparagine-linked glycosylation sites. AB - Of the large number of human alpha interferon genes identified, only one, Hu-IFN alpha H, contains potential asparagine-linked glycosylation sites. With the use of a new vector that permits convenient expression, site-specific mutation, and DNA sequencing, Hu-IFN-alpha H was expressed in Escherichia coli. The bacterial product which is not glycosylated is fully active demonstrating that the carbohydrate on this species is not required for antiviral activity. PMID- 3332546 TI - Effect of mouse interferon alpha/beta on the expression of H-2 (class I) antigens and on the levels of 2'-5' oligoadenylate synthetase activity in interferon sensitive and interferon-resistant Friend leukemia cell tumors in mice. AB - DBA/2 mice were injected intraperitoneally (i.p.) with interferon-sensitive 745 or interferon-resistant 3C1-8 Friend erythroleukemia cells (FLC) and then injected i.p. with mouse interferon alpha/beta. Interferon enhanced the expression of histocompatibility (H-2) antigens on individual 745 FLC within the peritoneum, but did not alter the expression of H-2 antigens on individual 3C1-8 FLC. Likewise, interferon treatment resulted in an increase in the level of 2'-5' oligo-adenylate (2-5A) synthetase activity in 745 FLC, but did not affect the level of activity in 3C1-8 FLC. These results provide evidence that the phenotype of interferon sensitivity or resistance of FLC does not change within the peritoneum. An incidental finding was that the basal level of 2-5A synthetase activity of in vivo passaged 745 cells was greater than that of 3C1-8 FLC. The finding that injection of mice bearing 745 FLC with antibody to mouse interferon alpha/beta reduced the level of 2-5A synthetase activity in these cells, but did not alter the level of 2-5A activity in 3C1-8 FLC, suggests that endogenous interferon in the peritoneum may have been the responsible factor. PMID- 3332545 TI - The alpha 2 (r) interferon in the treatment of hairy cell leukemia: progressive report of 25 cases. AB - Twenty-five patients with Hairy Cell Leukemia (HCL), eleven in post-splenectomy progressive disease, have been treated as out-patients with alpha 2 (r) Interferon (IFN) for twelve months. Eighteen patients completed the treatment: four achieved Complete Response (CR), twelve Partial Response (PR) and two Minor Response (MR). The response to IFN has been CR or PR in 89% of cases and MR in 11%. Even if the IFN effective dose and the length of treatment remain to be determined, IFN at relatively low dose seems to become the first treatment of choice in HCL patients. The remaining seven patients, still under treatment, already achieved PR at least. PMID- 3332547 TI - An enhanced chemiluminescent enzyme immunoassay for serum carcinoembryonic antigen based on a modification of a commercial kit. AB - A conventional colorimetric peroxidase end-point (ortho-phenylenediamine substrate), used in an enzyme immunoassay for carcinoembryonic antigen, employing plastic beads as solid support, has been replaced by a much faster (30 seconds versus 30 minutes) enhanced chemiluminescent assay for the peroxidase label. Para iodophenol was used to enhance the light emission from the peroxidase catalysed chemiluminescent reaction between luminol and hydrogen peroxide. Values for precision and carcinoembryonic antigen concentration obtained with the chemiluminescent and colorimetric versions of the immunoassay on 62 serum specimens were in good agreement. PMID- 3332548 TI - Rapid microbiology: applications of bioluminescence in the food industry--a review. AB - The bioluminescent assay of ATP is rapid and simple and may be used as an estimate of microbial numbers. It therefore shows great potential as a technique to provide information on the microbiological quality of a food within a few minutes, in comparison with conventional techniques, which provide results retrospectively. However, despite the advantages of speed and sensitivity, no food microbiologists are using the technique for routine quality control and hygiene monitoring. This review seeks to highlight the reasons for this, and to offer some ideas for future research to increase the acceptance of ATP assays within the food industry. PMID- 3332550 TI - Bioluminescence and chemoluminescence literature. PMID- 3332549 TI - Bioluminescence and chemoluminescence literature. PMID- 3332551 TI - Bioluminescent enzyme immunoassay for progesterone using monoclonal antibodies and glucose-6-phosphate dehydrogenase labels. AB - Bacterial luciferase, NAD(P): FMN oxidoreductase and anti-mouse immunoglobulin were co-immobilized on Sepharose 4B. This reagent together with a progesterone glucose-6-phosphate dehydrogenase conjugate and various anti-progesterone monoclonal antibodies was used to develop a non-separation bioluminescent immunoassay for progesterone. This monoclonal antibody based assay was sensitive and reliable and using the tracer progesterone-11-acetate-glucose-6-phosphate dehydrogenase, the majority of the monoclonal antibodies give a better sensitivity with this enzymatic tracer than that obtained with an iodinated tracer. In a second assay design progesterone-glutathione was co-immobilized with bacterial luciferase and NAD(P): FMN oxidoreductase on Sepharose 4B and three monoclonal antibodies were labelled with glucose-6-phosphate dehydrogenase. With aqueous progesterone standards, this assay gave comparable sensitivity to the bioluminescent enzyme immunoassay using the second antibody immunoadsorbent and to an RIA but was unsuitable for plasma samples. PMID- 3332552 TI - Bioluminescence and chemoluminescence literature. PMID- 3332553 TI - Effects of human recombinant CSF-GM and highly purified CSF-1 on the formation of multinucleated cells with osteoclast characteristics in long-term bone marrow cultures. AB - Several studies have suggested that the osteoclast is derived from a mononuclear precursor which is found in bone marrow. We have developed a system for studying the formation of osteoclast-like multinucleated cells in long-term bone marrow culture of baboon cells. Recombinant human CSF-GM and highly purified CSF-1, both of which stimulate the proliferation of monocyte/macrophage precursors, were found to increase the number of osteoclast-like cells formed in long-term bone marrow culture. CSF-GM stimulated multinucleated cell formation more consistently than CSF-1. The subsequent addition of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to cultures initially treated with CSF-GM or CSF-1 further increased multinucleated cell formation. Autoradiographic studies indicate that CSF stimulated multinucleated cell formation by increasing the proliferation of the precursor cell, and that the potentiating effect of 1,25-(OH)2D3 was caused by fusion of the increased numbers of precursors. These studies suggest that the interaction of locally produced colony-stimulating factors with circulating calcium regulating hormones may be important in the control of osteoclast formation and bone resorption. PMID- 3332555 TI - Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells. AB - Serum autoantibodies directed toward antigenic determinants on the surface of human parathyroid cells (PTAb-CS) have been demonstrated in a subset (8 of 23) of adult patients with idiopathic hypoparathyroidism (IHP). In sera from 3 of 8 patients with PTAb-CS, binding of these autoantibodies to their respective parathyroid cell surface antigen(s) resulted in marked inhibition of parathyroid hormone (PTH) secretion in an in vitro dispersed human parathyroid cell (dPTC) system. In 1 subject evaluated longitudinally, circulating levels of PTAb-CS, and the magnitude of the inhibitory effect on PTH secretion, temporally correlated with the clinical course of the hypoparathyroidism. These findings suggest a causative role for antibodies directed against cell surface antigens in parathyroid dysfunction in some cases of "autoimmune" hypoparathyroidism. PMID- 3332554 TI - The effect of 1,25-dihydroxyvitamin D3 on the cytoskeleton of rat calvaria and rat osteosarcoma (ROS 17/2.8) osteoblastic cells. AB - 1,25-dihydroxyvitamin D3 produces pronounced shape changes in fetal rat calvaria and osteosarcoma-derived (ROS 17/2.8) osteoblastic cells, characterized by retracting processes and cell rounding followed by aggregation of cells. The 1,25(OH)2D3 effect on ROS 17/2.8 morphology was determined morphometrically on scanning electron micrographs. The hormone effect was found to be dose dependent between 10(-12) and 10(-9) M. The shape changes appeared 12 h after hormone (10( 10) M) addition and were present in 80% of the ROS 17/2.8 cells and in 50% of the calvaria cells at 72 h. Cycloheximide at 1 microM, inhibited the hormone dependent change in morphology. The 1,25(OH)2D3 effects were partially mimicked by 10(-8) M 25(OH)D3 but not by 10(-10) M 25(OH)D3 or 10(-11)-10(-8) M 24,25(OH)2D3. 1,25-dihydroxyvitamin D3 also increased cell proliferation twofold at 14 days in serum-free medium. 1,25(OH)2D3 treatment produced changes in microfilament organization, visualized with rhodamine-conjugated phalloidin. Microfilaments were localized at the terminal attachment points and in the perinuclear region, and few if any, were seen in the retracting processes themselves. Estimation of cytoskeletal actin and myosin by gel electrophoresis of Triton X-100 nonextractable proteins showed a 30% reduction in these proteins in the hormone-treated cells. Microtubules visualized by indirect immunofluorescence showed no major changes in organization. Both colchicine and cytochalasin D altered the hormone-induced shape change, suggesting that both microfilaments and microtubules were required for this process. Thus, 1,25(OH)2D3 had pronounced effects on cell shape in osteoblastic cells, probably via de novo protein synthesis. These changes lead to rearrangement of the cytoskeleton, primarily the microfilaments. PMID- 3332557 TI - A contemporary psychodynamic approach to drug abuse treatment. AB - In contrast to early psychodynamic formulations of addictions which stressed pleasure seeking or self-destruction, a modern psychodynamic perspective places greater emphasis on understanding addicts' disturbances in regulating their internal emotional life and adjustment to external reality. Effective treatment rests on providing interventions and responses that appropriately respond to addicts deficits in regulating affects and behavior. Treatment modalities must keep needs for comfort, control, and safety as the highest priorities, especially initially, in considering the choice of treatment or combination of treatments which are adopted or prescribed. The concept of a primary care therapist is advanced in which a single clinician takes responsibility for holding patients to other interventions and for monitoring which elements or combinations are most helpful. Benefits, pitfalls, limitations, and risks are considered for individual psychotherapy, self-help groups (i.e., AA and NA), and group psychotherapy. The role of psychopharmacologic approaches are considered as they pertain to psychotherapy. PMID- 3332556 TI - Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women. AB - The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2 cholecalciferol on bone formation was studied in a randomized trial with 144 healthy postmenopausal women. Urinary excretion (UE) of 99m-technetium diphosphonate and serum alkaline phosphatase (AP) was determined before and then once a year for 2 years of treatment. Both estimates of bone formation showed highly significant decreases (p less than .001) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen, whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo. The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass, and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss. PMID- 3332558 TI - Psychobiology and the treatment of drug dependence: the biobehavioral interface. AB - In the past 15 years there has been an explosion of data on the multivariate nature of drug dependence. The complex relationship between addictive disorders and psychopathology has been better clarified. Certain Axis I and II diagnoses in DSM-III appear to occur more commonly in alcohol- and drug-dependent patients than in the general population, suggesting that they may serve as risk factors for the development of addictive disorders. Psychopathological symptoms also result during periods of chronic intoxication and may persist as secondary psychiatric disorders even in the absence of continued substance use. Behavioral research in human and animal models has begun to yield insights into the nature of dependence disorders and the importance of brain mechanisms of reinforcement to the addiction process. Inevitably, neural scientists are beginning to delineate the commonalities and differences in drug reinforcement across drug class. The research has begun to suggest pharmacological approaches to the treatment of drug dependence and withdrawal. This paper provides an overview of research on the psychobiology of drug dependence with implications for the clinician. PMID- 3332559 TI - Psychopharmacological trials in cocaine abuse treatment. AB - Recent research has produced encouraging preliminary data on general pharmacological treatments for cocaine abuse as well as on pharmacotherapies specific for cocaine abusers with Axis 1 psychiatric disorders. Pharmacotherapy trials with antidepressants, lithium, and stimulants in chronic cocaine abusers as well as recent clinical, diagnostic, and pre-clinical studies will be reviewed. Symptom presentation, severity of abuse, and phase of recovery are discussed as potential guides in treatment selection. PMID- 3332560 TI - Patient confidentiality statutes in Medicare & Medicaid fraud investigations. AB - The Medicare and Medicaid programs have been burdened with health care providers' fraudulent and abusive practices since their implementation in 1965. To help states discover and prevent Medicare and Medicaid fraud, Congress has enacted statutes permitting access to patients' medical records in investigations of fraud. The majority of states have enacted physician-patient and psychotherapist patient privilege statutes to protect confidential information from disclosure. Thus, the state's need for patient information conflicts with the patient's right of privacy. This Note discusses several court decisions that have wrestled with the tension between these two policies. The courts, after balancing the state interest in eliminating fraud against the patient's privacy interest, have often allowed disclosure of patient medical records. Although some courts have attempted to limit the extent of the information disclosed, few have set forth explicit standards to protect patient records from unwarranted disclosure of confidential information. This Note suggests guidelines for courts, legislatures and health care providers to uniformly limit the extent of this disclosure. PMID- 3332561 TI - Judicial determination of the sexual identity of post-operative transsexuals: a new form of sex discrimination. AB - Transsexualism is a condition in which an individual's psychological gender is the opposite of his or her anatomical sex. A "sex-change" operation can bring anatomical sex into line with gender, but it cannot create a new biological sex capable of procreation. The operation is expensive, dangerous and lengthy, yet in 1983 there were an estimated 6,000 post-operative transsexuals in the United States. Certain European countries have legislation recognizing the post operative transsexual's new sex. Case law in the United Kingdom and the United States, however, prevent post-operative transsexuals from gaining legal recognition. The author does see some hope, however, for a change in the trend against recognition of transsexuals' post-operative sex. This Article discusses the reasons behind this trend and concludes that the greater danger would be a consensus of medical opinion holding that sex-change surgery is unnecessary, questioning the very existence of post-operative transsexuals. Finally, the author calls for legislative action to remove judicially-imposed obstacles and to give legal recognition to the post-operative transsexual's new sex and identity. PMID- 3332562 TI - From Rogers to Rivers: the rights of the mentally ill to refuse medication. AB - Many individuals with mental illness wish to avoid psychotropic drugs, a type of treatment that may relieve their symptoms only at the risk of unpleasant, even permanent, side effects. In marked contrast to the widely-held view that most patients may refuse any treatment and that even patients with mental illness may reject other psychoactive interventions such as electroconvulsive therapy and psychosurgery, the courts and legislatures have been slow to recognize any right to refuse psychotropic drugs. This Article demonstrates that many of the justifications offered for forcing patients to take unwanted medications are inadequate and that unless treatment refusals are reviewed outside mental institutions, patients' rights will rarely receive appropriate deference. The author analyzes the federal and state litigation to determine whether the courts have fashioned meaningful relief for the mentally ill. The Article concludes that two recent United States Supreme Court decisions have made it impossible for the federal courts to provide adequate protection. By contrast, several state courts have responded to the needs and rights of patients with mental illness. PMID- 3332563 TI - Parental leave: the need for a national policy to foster sexual equality. AB - Working women are without substantial protection from the ramifications of pregnancy discrimination, and the opportunities for working men to take leave from work to participate in child care are limited. Recently, private businesses have begun implementing maternity or parental leave policies to address these problems. These policies are inconsistent, however, and a national parental leave program is needed to help women attain equal access to jobs and to provide men with the opportunity to participate in child care. This Note examines the historical background of pregnancy discrimination litigation and legislation, and highlights the gaps in the protection currently afforded women. It suggests that a federal parental leave policy may expand the scope of this protection, and attempts to gain insight and draw conclusions from analogous parental leave programs in foreign countries which may be used as models for a national program in the U.S. Such a program would benefit parents, children, and society by removing some of the obstacles to sexual equality. PMID- 3332564 TI - A randomized trial of dexamethasone and acetazolamide for acute mountain sickness prophylaxis. AB - Forty-seven climbers participated in a double-blind, randomized trial comparing acetazolamide 250 mg, dexamethasone 4 mg, and placebo every eight hours as prophylaxis for acute mountain sickness during rapid, active ascent of Mount Rainier (elevation 4,392 m). Forty-two subjects (89.4 percent) achieved the summit in an average of 34.5 hours after leaving sea level. At the summit or high point attained above base camp, the group taking dexamethasone reported less headache, tiredness, dizziness, nausea, clumsiness, and a greater sense of feeling refreshed (p less than or equal to 0.05). In addition, they reported fewer problems of runny nose and feeling cold, symptoms unrelated to acute mountain sickness. The acetazolamide group differed significantly (p less than or equal to 0.05) from other groups at low elevations (1,300 to 1,600 m), in that they experienced more feelings of nausea and tiredness, and they were less refreshed. These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness. Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone. This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease. PMID- 3332565 TI - Application of meta-analysis using an electronic spread sheet to exercise testing in patients after myocardial infarction. AB - Decision analysis is being applied to medical practice in order to achieve cost efficacy in health care delivery. Critical to this process is establishing the diagnostic and prognostic accuracy of medical tests and the effectiveness of interventions. Meta-analysis is an approach that applies statistical methods to groups of studies in order to extract consensus results. Electronic spreadsheets facilitate meta-analysis with their ability to store, sort, graph, and mathematically manipulate both the methodologic approaches and clinical findings of seemingly disparate studies. As an example, this application is demonstrated with an analysis of studies that were performed to evaluate the prognostic value of exercise testing in patients recovering from a myocardial infarction. The following conclusions were reached: (1) patients excluded from exercise testing have the highest mortality; (2) only subsets of patients have been tested resulting in highly selected patient samples that make findings difficult to generalize; (3) of the five exercise test responses, only an abnormal systolic blood pressure response and a poor exercise capacity predicted risk more frequently than by chance; (4) submaximal or predischarge testing has greater predictive power than postdischarge or maximal testing; and (5) exercise-induced ST segment depression only appears to be predictive of increased risk in patients with inferior-posterior myocardial infarctions. This approach to combining studies is important since even careful analysis of a single study cannot elucidate all of the complex interactions and selective biases that have occurred. However, comparison of many heterogeneous studies is at best an arduous and time-consuming task. This approach to using electronic spreadsheets to collate and analyze multiple studies facilitates recognition of the population characteristics, clinical factors, and methodologic considerations that affect outcome and allows the quick inclusion of additional studies for re-analysis and interpretation. PMID- 3332566 TI - Hypogonadotropic secondary amenorrhea in diabetes: effects of central opiate blockade and improved metabolic control. AB - The effect of improving diabetic control on secondary hypogonadotropic amenorrhea was investigated in patients with insulin-dependent diabetes mellitus (IDDM). Second, the hypothesis that increased central (hypothalamic) opiate inhibition may have been responsible for the suppression of gonadotropin-releasing hormone (GnRH) was tested by observing the effect of a four-hour naloxone infusion (1.4 mg/hour) on serum gonadotropin levels. All known causes of secondary amenorrhea were excluded before patients were eligible for the study. The median duration of amenorrhea was six years, and median body weight was 101 percent of ideal. After six months of improved metabolic control (n = 5) using intensified conventional therapy or continuous subcutaneous insulin infusion, the level of glycosylated hemoglobin dropped from 11.8 +/- 0.9 percent to 8.5 +/- 0.5 percent (p less than 0.005), and body weight increased from 60.5 +/- 1.8 kg to 64.7 +/- 1.4 kg (p less than 0.02). Menses did not, however, return in any patient. There was no significant change in serum levels of estradiol, progesterone, dihydroxyepiandrosterone, testosterone, prolactin, basal or GnRH-stimulated luteinizing hormone, or follicle-stimulating hormone. There was no change in the levels of luteinizing hormone or follicle-stimulating hormone during the naloxone infusion either during poor metabolic control or after six months of improved metabolic control. In conclusion, a form of secondary hypogonadotropic amenorrhea was identified in patients with IDDM that did not remit with sustained improvements in metabolic control. It did not appear to be mediated through increased central opiate tone. PMID- 3332567 TI - Visceral leishmaniasis in immunocompromised hosts. AB - Visceral leishmaniasis is infrequently reported in immunocompromised hosts; hence, the clinical manifestations and outcome of the disease in these patients are unknown. In a series of 10 patients with visceral leishmaniasis complicating renal transplantation (three), hematologic neoplasms (two), systemic lupus erythematosus (two), or infection with human immunodeficiency virus (three), typical hallmarks of kalaazar such as enlargement of spleen or hyperglobulinemia were absent in three and six patients, respectively. Extensive visceral involvement was noted by biopsies or autopsies in four patients. Diagnosis was made during evaluation for fever of unknown origin. Myriads of amastigotes were seen in bone marrow smears. Measurement of antibodies against Leishmania donovani was positive in each patient tested. Ultimately, three patients died, and chronic infections refractory to treatment developed in two other patients. Visceral leishmaniasis is a potentially fatal infection in immunocompromised hosts. Current antiparasitic therapy frequently fails to eradicate L. donovani from infected tissues. PMID- 3332568 TI - Prevention of fungal sepsis in patients with prolonged neutropenia: a randomized, double-blind, placebo-controlled trial of intravenous miconazole. AB - Patients treated with cytotoxic therapy expected to produce neutropenia lasting two or more weeks were randomly assigned in a double-blind study to receive intravenous miconazole or placebo concomitant with empiric antibiotics to test whether miconazole can prevent fungal sepsis. The study drug was initiated at the time of first fever along with antibiotics and was continued until neutropenia resolved, fungal sepsis occurred, or persistent or recurrent unexplained fever after six or more days prompted substitution of the study drug by amphotericin B. Two hundred eight treatment courses in 180 patients were evaluated. Fungal sepsis occurred in only one patient receiving miconazole compared with eight patients receiving placebo (p = 0.03). Fatal fungal sepsis occurred in four patients receiving placebo and in none of the patients receiving miconazole (p = 0.08). There was no evidence for the development of resistance to polyenes or imidazoles in fungal isolates recovered from patients in this randomized trial or an increase in Aspergillus infections in patients who received miconazole in this randomized trial or in 121 subsequently treated patients who received unblinded use of miconazole. Thus, intravenous miconazole was more effective than placebo in preventing fungal sepsis in patients with chemotherapy-induced prolonged neutropenia. PMID- 3332569 TI - Systemic treatment for prostate cancer. AB - Prostate cancer is a leading cause of cancer mortality in adult men. The majority of patients have subclinical systemic disease at diagnosis and will eventually require systemic therapy for palliation of symptoms. Recent development of new hormonal treatment options (e.g., gonadotropin-releasing hormone analogues and estramustine) has yet to demonstrate potential for improving the therapeutic index or for lengthening survival over results achieved with traditional modalities (i.e., supplemental estrogens or castration). Chemotherapeutic agents have demonstrated palliative efficacy and are being tested in multidrug regimens and in combination with hormones. At the present time, the optimal use of cytotoxic drugs remains undefined, since recently published studies have shown neither that combination chemotherapy is superior to single agents nor that chemo hormonal therapy produces more favorable results than hormonal treatment alone. PMID- 3332570 TI - Gorham's syndrome: a case report and review of the literature. AB - Gorham's syndrome is a rare disorder involving a proliferation of vascular channels associated with extensive loss of bony matrix. A case report is presented with a review of the 97 previously reported cases. The age of patients at presentation has ranged from less than one to 75 years (mean: 27 years). Sixty four percent have been men. Fifty-seven percent have had a history of prior trauma. Laboratory values for systemic measures have usually been normal. The disease usually arrests spontaneously, but this is unpredictable. Sixteen patients (16 percent) have died of the disorder, with 10 deaths due to chest wall involvement, three to spinal cord transection, two to sepsis, and one to asphyxia and aspiration. Although the mechanism of bone loss is unknown, osteoclasts were focally increased in the case described herein. Further information and investigation are needed to better understand this unusual disorder. PMID- 3332571 TI - Heritable syndrome of pseudoxanthoma elasticum with abnormal phosphorus and vitamin D metabolism. AB - A patient with pseudoxanthoma elasticum was documented to be hyperphosphatemic and mildly hypercalcemic for six years. Complications included metastatic calcification, absorptive hypercalciuria, and renal insufficiency. The 1,25 dihydroxyvitamin D value was elevated, despite normal serum parathyroid hormone values, high serum phosphate levels, and renal insufficiency. Either increased dietary calcium or prednisone seemed to suppress the 1,25-dihydroxyvitamin D value. Nephrolithiasis or abnormalities suggestive of pseudoxanthoma elasticum occurred in the patient's father, daughter, and several siblings, suggesting a distinct familial syndrome in which connective tissue changes are accompanied by abnormalities of phosphorus and vitamin D metabolism that may resemble those in the syndrome of familial tumoral calcinosis. Nine similar cases were described before 1970. PMID- 3332573 TI - Controlled study of renal osteodystrophy in patients undergoing dialysis. PMID- 3332572 TI - Invasive Scopulariopsis in the immunocompromised host. AB - Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient. PMID- 3332574 TI - Multicenter comparison of the nifedipine gastrointestinal therapeutic system and long-acting propranolol in patients with mild to moderate systemic hypertension receiving diuretics. A preliminary experience. AB - The efficacy and safety of nifedipine in a gastrointestinal therapeutic system (GITS) push-pull osmotic pump formulation was compared with long-acting propranolol in 49 patients with mild to moderate hypertension already receiving diuretics. Using a two-week placebo run-in, double-blind study design, patients were randomly assigned to receive nifedipine GITS (n = 24) in doses of 30 mg, 60 mg, or 90 mg once daily; or long-acting propranolol (n = 25) in doses of 80, 160, or 240 mg once daily. Previous diuretic therapy was continued. Sitting and five minute standing blood pressure and heart rate measurements were made 24 hours after dosing. At the endpoint of treatment, both nifedipine GITS and sustained release propranolol reduced blood pressure compared with placebo (p less than 0.001) in the sitting and standing positions. Nifedipine GITS was more effective in lowering standing systolic blood pressure than was propranolol (p less than 0.02). Propranolol caused a greater reduction in resting heart rate than did nifedipine GITS (p less than 0.003). Both drugs were well tolerated. Nifedipine GITS is an effective and safe once-daily drug for use in patients with hypertension who are already receiving diuretics, may be more effective than sustained-release propranolol, and may be better tolerated than conventional nifedipine capsules. PMID- 3332575 TI - Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system. AB - The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy. PMID- 3332576 TI - [Study of nodular lesions of the thyroid using high-resolution echography and echo-guided biopsy]. PMID- 3332577 TI - [Chemodectomas: our experience]. PMID- 3332578 TI - [Echography of echo-guided cytoaspiration in the preoperative diagnosis of primary hyperparathyroidism]. PMID- 3332579 TI - [Intraoperative echography as an aid in the surgery of renal lithiasis]. PMID- 3332580 TI - [Endoluminal echography in the preoperative evaluation of the patient with cancer of the rectum and early diagnosis of local recurrence]. PMID- 3332581 TI - [Echography in the study of expansive processes of the parotid]. PMID- 3332582 TI - [Diagnostic and therapeutic problems in carcinoma of the renal pelvis. Comparison of traditional methods and modern technological contributions]. PMID- 3332583 TI - [Use of hyperbaric oxygen therapy in surgery]. PMID- 3332584 TI - [Surgery of the extracranial carotid. Indications and technics]. PMID- 3332585 TI - [Color vision]. PMID- 3332586 TI - [Artificial intelligence and ocular sensory electrophysiology]. PMID- 3332588 TI - [Contrast sensitivity]. PMID- 3332589 TI - [Treatment of blepharospasm: injection of botulinum toxin or surgical treatment?]. PMID- 3332590 TI - [Preventive treatment of retinopathy of prematurity]. PMID- 3332587 TI - [Calibration of the implant]. PMID- 3332591 TI - [AIDS in ophthalmology]. PMID- 3332592 TI - [Respective indications for echography, scanning and MRI in diseases of the eye and orbit]. PMID- 3332594 TI - [Epikeratoplasty]. PMID- 3332593 TI - [Respective indications for echography, scanning and MRI in diseases of the intra cranial optic pathways]. PMID- 3332595 TI - [The macular edema of aphakia and pseudo-aphakia]. PMID- 3332596 TI - [Measurement of stereoscopic vision]. PMID- 3332597 TI - Actual data in human Mycoplasma infections. PMID- 3332598 TI - Studies concerning the utilization of the cell culture test with CHO-K1 cells for the identification of enterotoxigenic enterobacteria (ETEB)-strains. PMID- 3332599 TI - Functional electrical stimulation and the rehabilitation of the spinal cord injured patient. PMID- 3332600 TI - Rehabilitation management of the burn patient. PMID- 3332601 TI - Management of pain after thermal injury. PMID- 3332602 TI - Physical rehabilitation of the cancer patient. PMID- 3332604 TI - Neuropsychological assessment in brain injury rehabilitation. PMID- 3332603 TI - Psychological considerations in rehabilitation of the cancer patient. PMID- 3332605 TI - [Voltaire and medicine]. PMID- 3332606 TI - Prevention of neonatal intraventricular hemorrhage. PMID- 3332607 TI - Treatment of neurosyphilis. PMID- 3332608 TI - The use of cyclophosphamide to treat multiple sclerosis. PMID- 3332609 TI - Flunarizine, a calcium-entry blocker, in childhood migraine, epilepsy, and alternating hemiplegia. PMID- 3332611 TI - Double-blind controlled study of pergolide mesylate in the treatment of Parkinson's disease. PMID- 3332610 TI - Low-dose bromocriptine in the early phases of Parkinson's disease. AB - The effect of bromocriptine at doses up to 20 mg/day was studied in a single blind format with a placebo phase in 15 Parkinson's disease patients with mild-to moderate disability who had not been previously treated with levodopa. For the 11 patients who completed the 9 month trial, both Northwestern University Disability Scale and Columbia University Rating Scale scores were significantly reduced during bromocriptine therapy, when compared with either baseline or placebo scores. Two patients improved greater than 50% and had no side effects. Transient side effects appeared in four patients. Bromocriptine at doses of 20 mg/day or below may yield effective symptomatic improvement in de novo parkinsonism and may be considered as the initial treatment in young parkinsonian patients with only mild-to-moderate disability. PMID- 3332612 TI - Neurotoxicity of ethanol during prenatal development. PMID- 3332613 TI - Nimodipine in ischemic stroke. PMID- 3332614 TI - Withdrawal of anticonvulsant drugs in seizure-free epileptic patients. PMID- 3332615 TI - Pindolol-induced tremor. PMID- 3332616 TI - Cognitive function, cognitive style and life satisfaction in a 68-year-old male population. AB - A representative sample of 68-year-old men living in the city of Malmo, Sweden, was examined by means of psychological tests and questionnaires regarding cognitive capacity, cognitive style as an expression of personality, and life satisfaction. Reference values for these parameters are presented, and a continuous cohort increase of verbal ability could be identified in this age group. That the prevalence of cognitive reduction was found to be surprisingly high is tentatively interpreted as reflecting an underdiagnosis of these symptoms as concomitant to other diseases in the general population. Earlier results supporting the concept of terminal decline could not be replicated. The reason for this might be that the present population was somewhat younger than those earlier investigated. Contrary to expectation, life satisfaction did not correlate to either cognitive reduction or cognitive style. It had, however, a positive correlation to measures of fluid intelligence. PMID- 3332617 TI - Issues in the study of the quality of the elderly mother-adult daughter relationship. AB - The quality of intergenerational relationships seems to be a relevant factor in assessing both the family's capacity to continue to provide care for elderly family members and the effectiveness with which it performs caregiving functions. The purpose of this paper is first, to raise several questions with regard to the quality of family ties to which we believe research should address itself. These include the implications of recent sociodemographic trends for quality, and the effects which variations in quality may have for various dimensions of the caregiving process. The literature and research on qualitative aspects of family relationships seems to suffer from basic conceptual and methodological limitations. Thus, this paper also aims at presenting a multidimensional conceptualization of quality which we believe is essential for identifying those specific aspects of relationships most significant in their impact on caregiving. PMID- 3332618 TI - Differential accumulation of oocyte nuclear proteins by embryonic nuclei of Xenopus. AB - Oocyte nuclear proteins of Xenopus are distributed into the cytoplasm of the maturing egg after germinal vesicle breakdown. Later they are found in all cell nuclei of the embryo. At early stages of development, different nuclear proteins behave differently. A class of 'early shifting' antigens is accumulated by pronuclei and cleavage nuclei, whereas others appear to be excluded from the nuclei at early stages but are shifted into the nuclei at blastula or during and after gastrulation. Accumulation of 'late-shifting' nuclear antigens is a gradual process and occurs during a period characteristic of each protein. Multiple artificial pronuclei can be formed after injection of sperm nuclei, erythrocyte nuclei or pure lambda-DNA into unfertilized eggs. The artificial pronuclei accumulate early- but not late-shifting proteins. Early-migrating proteins rapidly accumulate into the germinal vesicle after de novo synthesis in the oocyte, indicating that the efficiency of translocation into nuclei is an intrinsic property of each protein. Artificial extension of the length of the cell cycle before midblastula transition does not lead to accumulation of the late-shifting nuclear antigens investigated. PMID- 3332619 TI - Experimental study on modified acrylic resin materials. PMID- 3332620 TI - Tissue reaction to different materials implants. PMID- 3332621 TI - Geographic study of bacterial growth at the cervical margin of crowns and fixed prosthodontics. PMID- 3332622 TI - [Densitometric in vitro study on photographic subtraction of periodical dental radiographs]. PMID- 3332623 TI - [Are there safe established effects of soft lasers in periodontal treatment?]. PMID- 3332624 TI - [Juvenile periodontitis: healing following frozen cancellous bone allografts]. PMID- 3332625 TI - [Analysis of inflammatory infiltrates with monoclonal antibodies in various stages of inflammation of the gingival margin]. PMID- 3332627 TI - The effect of the sex chromosomes on dental crown morphology: a review. PMID- 3332626 TI - Autogeneous dermal grafts in temporomandibular joint surgery. PMID- 3332628 TI - Venous complications of the thoracic outlet syndrome. PMID- 3332629 TI - Quantitative assessment of vasospasm by Doppler spectrum analysis in patients with primary Raynaud's phenomenon. AB - The aim of the study was to investigate whether increased peripheral resistance which is supposed to exist in patients with primary Raynaud's phenomenon, can be quantified by using parameters of Doppler spectra of flow in the ulnar and radial arteries. A group of 24 patients with this abnormality were compared with a matched group of 24 normal subjects. Doppler spectra were analysed according to the methods of Fronek, Gosling and by Fast Fourier Transform analysis. The Doppler spectra obtained from patients at room temperature were very different from those in normal subjects, showing characteristic wave-forms with multiple oscillations in 92% of the patients. All three analysing techniques demonstrated significant differences between the two groups, which can be attributed to increased peripheral vascular resistance in the patient group. The results of this study emphasize the value of analysis of Doppler spectra obtained from ulnar and radial arteries in the assessment of peripheral vascular resistance in vasospastic disease. PMID- 3332630 TI - Asymptomatic carotid stenosis--is prophylactic surgery indicated? PMID- 3332631 TI - Low dose intra-arterial streptokinase and acylated plasminogen-streptokinase activator complex: a retrospective review of two thrombolytic regimes in recent peripheral arterial ischaemia. AB - Thrombolytic therapy was used for 57 patients with acute and sub-acute lower limb arterial ischaemia. In the first 34 patients a new thrombolytic agent, acylated plasminogen-streptokinase complex (BRL 26921) was assessed. Following this, 23 patients received low dose intra-arterial streptokinase. The two thrombolytic regimes have been analysed retrospectively. There were differences observed between the two groups in the type of patients treated and in the severity of limb ischaemia. Of the patients receiving BRL 26921, five (15%) had complete, and three (9%) partial lysis of the occluding thrombus. Serious bleeding occurred in six (18%) and minor bleeding in ten (29%) patients. After 30 days, twelve patients (35%) had limb salvage and eleven (32%) had died. Fifteen patients (65%) receiving intra-arterial streptokinase had lysis of the occluding thrombus. Minor bleeding was observed in three patients (13%). After 30 days, 15 (65%) had limb salvage and three (13%) had died. Patients receiving BRL 26921 had a significantly greater reduction in plasma fibrinogen and plasminogen concentrations during treatment which may have accounted for the bleeding complications. At the dose used, BRL 26921 had no demonstrable fibrinogen sparing effect. Improved lysis rates with fewer bleeding complications might be achieved by reducing the dose of BRL 26921. Low dose intra-arterial streptokinase has been confirmed as a safe, effective method of thrombolysis in recent peripheral arterial ischaemia. PMID- 3332632 TI - Duplex scanning and plaque histology in cerebral ischaemia. AB - Twenty-seven patients undergoing carotid endarterectomy (21 M, 6 F), with a mean age of 62 years, were studied by carotid ultrasound imaging, angiography, and histological examination of endarterectomy specimens, including Perl's stain to detect haemorrhage more than a week old. Haemorrhage into a plaque was seen histologically in 21 patients (78%), compared with 19 (70%) diagnosed preoperatively as echolucent heterogeneous plaques on ultrasound imaging. The remainder were echogenic homogeneous, fibrous plaques. In only one case was the nature of the plaque diagnosed by contrast arteriography. Excised endarterectomy specimens were inspected independently of the ultrasound assessment to determine whether the site of haemorrhage communicated with the base of an atherosclerotic ulcer. Communicating haemorrhages were present in 9 of 11 with episodic symptoms and non-communicating haemorrhages in 7 of 10 patients with a single cerebrovascular event. Perl's stain showed recent haemorrhage in 7 of 11 patients with multiple symptoms, and old haemorrhage in 9 of 10 patients with a single event. These findings suggest that ultrasonically heterogeneous communicating carotid plaques are symptomatically more active than homogeneous non communicating plaques. PMID- 3332633 TI - The influence of patent branches on in situ vein graft haemodynamics. AB - The effect of patent graft branches on intra-operative graft flow and pressure has been studied in 50 patients undergoing in situ vein femoro-distal arterial bypass. In 35 grafts in which patent branches in the calf and thigh were preserved as arteriovenous fistulae, release of temporary branch occlusion increased mean proximal graft flow by 178.6% in 32, and reduced distal graft flow by 49.7% in 30. Seventeen limbs had thigh fistulae only: release of temporary fistula occlusion produced a fall in distal graft flow in only three. We identified three types of fistula: (a) cutaneous branches usually found in the thigh, which do not affect graft flow; (b) perforator branches which increase graft inflow but have no effect on distal graft flow: (c) perforator branches which increase graft inflow and decrease graft outflow, and are most frequently found in the calf. Discrimination between these haemodynamically differing branches at operation proved difficult. Since patent branches never improve distal graft flow and may reduce it, we recommend that all fistulae are ligated at operation. PMID- 3332635 TI - [Fighting marginal leakage. Adhesive for exact bonding]. PMID- 3332634 TI - Failure of duplex scanning to demonstrate an anomalous branch of the internal carotid artery. PMID- 3332636 TI - [Masterly dental technic. The way to the "Golden Parallelometer"]. PMID- 3332637 TI - [Assumptions with functional complete dentures. Determination of relations in edentulous persons]. PMID- 3332638 TI - Hepatitis B. PMID- 3332639 TI - A toothbrush for overdentures. PMID- 3332640 TI - Dentistry, the CT scan and fossil man. PMID- 3332641 TI - Dentistry in the year 2000. Dental caries: problem solved? PMID- 3332643 TI - Prosthetic treatment of cleft palate patients. PMID- 3332644 TI - The evolution of clinical imaging. PMID- 3332642 TI - Herpes zoster and post-herpetic neuralgia: diagnosis and management. PMID- 3332645 TI - Bonded attachments in the management of palatal and high buccal canines. PMID- 3332647 TI - [Role of ambulatory electrocardiography in the evaluation of interventions: rehabilitation of a patient who has undergone surgery]. AB - The authors relate their own experience with 24 hr Holter monitoring in course of cardiac rehabilitation after coronary bypass surgery as well as after valvular replacement. As regards patients after coronary surgery they report the experience they got in the evaluation of heart rate trend and cardiac arrhythmias as well as in silent ischemia study. About this last problem 116 patients with signs of ischemia both in stress test and in Holter recording are considered out of 491 who had undergone coronary surgery. Ischemia during 24 hr Holter monitoring develops at an heart rate lower than effort ischemia. Holter monitoring proves to be very useful also in patients after valvular replacement to study arrhythmias and to check drugs' efficacy. After displaying the results concerning arrhythmias of 24 hr Holter electrocardiograms recorded in 207 randomized patients who had undergone valvular replacement 15 days before, the authors dwell upon the use of Holter electrocardiography in 82 valvular patients after pharmacological cardioversion and show that major arrhythmias get a clear reduction thanks to rehabilitation. PMID- 3332646 TI - [Role of Holter electrocardiogram in the evaluation of anti-arrhythmia therapy]. AB - Statistical models may be useful in order to evaluate antiarrhythmic treatment and to distinguish between drug efficacy and spontaneous variability of premature ventricular depolarizations. Analysis of variance and linear regression analysis have been both proposed for documenting antiarrhythmic efficacy. Holter/exercise approach has been designed as noninvasive method of drug testing. So far only one group has reported the long-term outcome of patients managed using this approach. Patients with malignant ventricular arrhythmias in which efficacy was achieved had better chance of surviving during follow-up than did the nonresponder patients. In addition to acute drug testing, chronic trials have been undertaken. One group has reported the long-term results in 124 drug trials and the efficacy was controlled by Holter monitoring. Cumulative probability of survival at 24 months was better for responders than for nonresponders (P less than 0.001). Perspective trials with antiarrhythmic drug are being concluded, such as CAPS and TEST. The results are imminent. Additional aspects to be considered are that critical suppression of premature ventricular depolarizations by Holter does not predict long-term remission of malignant ventricular arrhythmias. Comparison of follow-up results by programmed electrical stimulation and by Holter monitoring are not similar; retrospective non randomized studies show that programmed stimulation was superior to ambulatory monitoring in predicting drug efficacy, or that clinical outcome in patients whose regimen had been found ineffective by programmed stimulation, was as good as the outcome in patients effectively controlled by Holter monitoring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332648 TI - Pituitary adenomas. AB - This review highlights various aspects of the new functional classification of pituitary adenomas which is based on detailed immunohistochemical and ultrastructural analysis and correlation with clinical and biochemical findings. In addition, current investigation of the non-hormonal aspects of these tumours is discussed, including the application of flow cytometry in tumour ploidy studies. PMID- 3332649 TI - Research methodology in special education: a framework for practice. PMID- 3332650 TI - Enzyme systems initiating replication at the origin of the Escherichia coli chromosome. AB - More than ten proteins are known to participate in replication of plasmids bearing the unique origin of the Escherichia coli chromosome (oriC). Initiation of replication of oriC plasmids has been resolved into five separable stages. An initial complex formation (Stage I) requires an oriC plasmid, dnaA protein and HU protein. In the presence of ATP at a temperature of greater than 28 degrees C, a dnaB-C protein complex interacts to form a prepriming complex (Stage II). This is followed by extensive unwinding of the template that depends on the further addition of gyrase and single-strand binding protein (SSB) (Stage III). Hydrolysis of an rNTP by dnaB protein (a helicase action) and of ATP by gyrase (a swivelling action) drives the extreme unwinding of the template. This unwound template-protein complex is the substrate for priming by primase (Stage IV) and elongation by DNA polymerase III holoenzyme (Stage V). Priming of all DNA chains is done by primase; RNA polymerase functions in template activation rather than priming. DNA polymerase III holoenzyme, composed of at least seven subunits, synthesizes the DNA chains. The alpha subunit is the polymerase, the epsilon subunit is the 3'----5' exonuclease; alpha + epsilon is the proofreading activity. Following the synthesis of new DNA chains, DNA polymerase I and ribonuclease H remove the RNA primers, polymerase I fills the gaps, and ligase seals the daughter strands (Stage VI). Replication produces plasmids identical in structure and sequence to the initial template. PMID- 3332652 TI - Latent cellular oncogenes: the paradox dissolves. AB - The 20 known transforming onc genes of retroviruses are defined by sequences which are transduced from cellular genes, termed proto-onc genes. Based on these sequences, viral onc genes have been postulated to be transduced cellular cancer genes and proto-onc genes have been postulated to be latent cancer genes that can be activated from within the cell, to cause virus-negative tumours. The hypothesis is popular because it promises direct access to cellular cancer genes. However the existence of latent cancer genes presents a paradox since such genes would be most undesirable for eukaryotes. The hypothesis predicts (i) that viral onc genes and proto-onc genes are isogenic, (ii) that expression of proto-onc genes induces tumours, (iii) that activated proto-onc genes transform diploid cells upon transfection, like viral onc genes, and (iv) it predicts diploid tumours. As yet, none of these predictions is confirmed. Instead: (i) Structural comparisons between viral onc genes, essential retroviral genes, and the proto onc genes show that all viral onc genes are indeed new genes, rather than transduced cellular cancer genes. They are genetic hybrids put together from truncated viral and truncated proto-onc genes. (ii) Proto-onc genes are frequently expressed in normal cells. (iii) To date, not one activated proto-onc gene has been isolated that transforms diploid cells. (iv) Above all, no diploid tumours with activated proto-onc genes have been found. Moreover the probability of spontaneous transformation in vivo is at least 10(9) times lower than predicted from the mechanisms thought to activate proto-onc genes. Therefore the hypothesis, that proto-onc genes are latent cellular oncogenes, appears to be an over-interpretation of sequence homology to structural and functional homology with viral onc genes. Here is is proposed that only rare truncations and recombinations, that alter the germline configuration of cellular genes, generate viral and possibly cellular cancer genes. The clonal chromosome abnormalities that are consistently found in tumour cells are microscopic evidence for rearrangements that may generate cancer genes. The clonality indicates that the tumours are initiated with, and possibly by these abnormalities as predicted by Boveri in 1914. PMID- 3332651 TI - DNA and protein interactions in the regulation of plasmid replication. AB - As for bacterial and animal viruses that employ different mechanisms for their duplication in a host cell, plasmids have evolved different strategies to assure their hereditary stability or maintenance at a specific copy number during cell growth and division. A characteristic feature of plasmid replication control, however, is an involvement of one or more negatively controlling elements. Furthermore, a majority of the bacterial plasmids examined to date contain direct nucleotide sequence repeats at their origin of replication and encode a replication protein that binds to these repeat sequences. The binding of the replication protein (pi protein) specified by the antibiotic resistance plasmid R6K to a set of 22 base pair direct nucleotide sequence repeats is required for the initiation of replication at each of three origins of replication (alpha, beta and gamma) within a 4 Kb segment of R6K. The pi initiation protein is multifunctional in that it has both positive and negative activities in both controlling the initiation of replication and autoregulating its own synthesis. Similarly, the direct repeats of plasmid R6K and several other plasmid systems play more than one role in plasmid replication. These repeats, termed iterons, are not only required for origin activity but also exert a negative effect on plasmid copy number possibly as a result of their 'titration' of a plasmid encoded replication protein. The properties of plasmid replication proteins and direct nucleotide sequence repeats that are important for their opposing positive and negative roles in the regulation of the initiation of replication are described with particular emphasis on plasmid R6K of Escherichia coli. PMID- 3332653 TI - The hepatitis-B viruses: molecular biology and recent tissue culture systems. AB - In this report we summarize what is known about the molecular biology of the hepatitis-B viruses. In the first part we describe the general properties of these viruses, their structure and their replication strategy. In the second part we discuss the most recent attempts at the establishment of tissue culture systems allowing the study of the virus/host cell interactions in vitro. In addition we present experimental data from our laboratory in which we show that new synthesis of viral proteins can be studied in vitro either by biochemical analysis of already infected cells or after experimental infection. PMID- 3332654 TI - Structure and replication of caulimovirus genomes. AB - In this paper the current state of knowledge of the replication of cauliflower mosaic virus (CaMV) is reviewed and the DNA intermediates and enzymes involved in replication are discussed. Based on this information a model for the replication complex is developed. In this model it is suggested that replication complexes resemble virus particles and that, in their assembly, there are close interactions between the inclusion body protein, the virus coat protein, the replicase enzyme, the tRNA primer and the 35S RNA template. The similarities between CaMV replication complexes and those of retroviruses are discussed, and we extend this discussion to a comparison between CaMV and reverse transcribing elements. PMID- 3332655 TI - Actin cortex and microtubular system in morphogenesis: cooperation and competition. AB - Actin cortex and microtubules determine two different types of morphological organization of the cytoplasm. Cooperation and competition between these two organizations may produce a diversity of final forms. Actin cortex alone, without the other cytoskeletal systems, is sufficient for the organization of vectorized pseudopod-forming cytoplasmatic units termed 'actinoplasts'. Reversible segregation of cytoplasm into actinoplasts and microtubule-rich stable domains ('tubuloplasts') is suggested to play an important role in many types of morphogenesis. Segregation of this type can be induced in fibroblasts of certain lines by the tumour promotor, tetradecanoyl phorbol-acetate (TPA). Self organization of each actinoplast leads to the development of microfilament bundles associated with focal contacts. Analysis of the evolution of these bundle contact structures during spreading of mouse fibroblasts suggests that their patterns are determined by the degree of centripetal tension within the actin cortex; the microtubular system stabilizes these patterns. Pseudopodial activity of the edges of the actinoplasts can be controlled by environmental factors. One particular type of control, i.e. the effect of cell-cell contact, is discussed. Actin cortex and microtubules seem to have alternative effects on the distribution of vimentin-containing intermediate filaments. PMID- 3332656 TI - Leucocyte locomotion: behavioural mechanisms for accumulation. AB - The behavioural mechanisms that may contribute to the accumulation of leucocytes (e.g. in inflammatory sites) are reviewed. Almost all of the neutrophils and monocytes of blood are motile and capable of migrating into tissues, but many blood lymphocytes are non-motile. They can however be induced to acquire locomotor capacity by culture with growth activators such as anti-CD3 antibodies. Resting lymphocytes become motile after entering the G1 phase of the cell cycle. Chemotaxis is well-studied in neutrophil leucocytes and is an efficient mechanism for cell accumulation. Possible mechanisms by which leucocytes respond to attractant gradients are discussed. Non-chemotactic mechanisms may also lead to cell accumulation, and evidence is reviewed that shows that an adhesive trapping mechanism causes leucocytes that cross an adhesion boundary to accumulate in the absence of a chemotactic gradient. Leucocytes migrating through aligned connective tissue show contact guidance in the axis of alignment of the tissue. Contact guidance can reinforce or hinder the response of neutrophils to chemotactic gradients. PMID- 3332657 TI - Cell motility and the problem of anatomical homeostasis. AB - The locomotion of tissue cells need not be invasive or disrupt normal tissue geometry, as occurs in cancer. The normal relationship between anatomical structure and cell locomotion is exactly the reverse, with motility serving to create and maintain the structures of the body. This relationship is most extreme in sponges, where time-lapse films show that the cells move about continually in patterns that restructure these animals' simple anatomy. The cells choose their position according to their differentiated cell type, which is the opposite of what is usually assumed to occur in development and has important implications for the functional significance of histotypic cell sorting. A particular type of cellular force that seems to be important in morphogenesis is the traction that all motile tissue cells exert. This traction can be studied by culturing cells on very thin sheets of silicone rubber, so that the locations and variations in the cellular forces are made visible by the wrinkles they produce in the rubber substratum. One finding has been that the traction forces exerted by untransformed fibroblasts are very much stronger than is needed for their own locomotion, but are well adapted for the function of rearranging and aligning collagen fibres to form structures like ligaments, tendons and muscles. These forces are found to be greatly weakened by neoplastic transformation, however, suggesting that malignant invasiveness results from some sort of deflection of cell traction forces from their proper morphogenetic functions, so as to produce uncontrolled invasion. To explain how motile cells create and maintain structures, as well as how their locomotion sometimes becomes perverted into the form of cancerous invasiveness, what seems to be needed is an extension of the concept of homeostasis to apply to the control of geometric relations between cells. This task may not be easy; one obstacle is the widespread belief that asymptotic stability implies the minimization of free energy. Instead, I suggest that stability results from balance of opposing forces within tissues, and that genes control which anatomical shapes will exist by determining the rules by which the relative strengths of these forces vary as functions of shape: to control shape, one must control the way forces vary with shape. PMID- 3332658 TI - Qualitative and quantitative analysis of tumour invasion in vivo and in vitro. AB - Qualitative and quantitative methods for the analysis of invasion in 'natural' and in experimental tumours in vivo and in vitro are reviewed. In human tumours the functional consequences of invasion were evaluated histologically through staging on the basis of depths of invasion and through the presence of tumour cells inside vessels. Antibodies against components of the basement membrane have facilitated the definition of minimal invasion. With new probes derived from oncogene research the search for molecular differences between invasive and non invasive parts of the tumour has begun. Since the same methods as those used for analysis of natural tumours also apply to experimental tumours in vivo, the major advantage of the latter is the possibility of manipulation. We have described a new mesenterium assay that may permit the selection of invasive cells from non invasive ones in transfection experiments. Invasion relative to growth as a function of time was quantified in the kidney invasion test. In three-dimensional confrontations between embryonic chick heart fragments and invasive cells, we have used both a subjective grading and a qualitative computer-assisted image analysis of serial histological sections to score invasion. In two-dimensional confrontations supplementary methods could be applied, since such confrontations permitted direct observations on living cultures. In a variety of natural and experimental tumours, ultrastructural analysis, transmigration in two-compartment chambers, and release of metabolic label have demonstrated the role of motility and of lytic activity in tumour invasion. PMID- 3332659 TI - Foetal-to-adult transitions in fibroblast phenotype: their possible relevance to the pathogenesis of cancer. AB - We have previously shown that the migration of foetal, adult and transformed fibroblasts into three-dimensional collagen gels is differentially affected by plating cell density. We now present data indicating that the migration of these fibroblasts is also differentially affected by local cell density in microdomains of the gel surface. In this article we discuss the possible biochemical and behavioural mechanisms that may contribute to the different migratory phenotypes expressed by foetal, adult and transformed fibroblasts; these include: (1) cell induced alterations in the orientation and or packing density of collagen fibres in the gel; (2) deposition of specific matrix macromolecules by the fibroblasts; (3) social interactions between the cells; and (4) secretion of soluble factors affecting cell migration. We show that foetal fibroblasts secrete a migration stimulating factor (MSF) not produced by adult cells. Incubation of adult fibroblasts in the presence of MSF induces these cells to express a foetal-like migratory phenotype. Foetal fibroblasts undergo a spontaneous foetal-to-adult transition in migratory phenotype after prolonged passage in vitro; this transition is accompanied by a cessation in MSF production. MSF appears to promote fibroblast migration at high cell density by stimulating the deposition of hyaluronic acid in the extracellular matrix. Recent studies have indicated that skin fibroblasts from cancer patients display certain behavioural abnormalities characteristic of transformed and/or foetal cells. In this regard, we have shown that skin fibroblasts from cancer patients commonly express a foetal-like phenotype with respect to migratory behaviour and secretion of MSF: it is of interest to note that these cancer patient fibroblasts are indistinguishable from normal adult cells in other respects, such as morphology in confluent culture. On the basis of these observations, we suggest that: (1) fibroblasts in certain individuals fail to undergo normal foetal-to-adult transitions in a number of phenotypic characteristics; and that (2) the disruption in epithelial-mesenchymal interactions caused by the continued presence of these foetal-like fibroblasts in the adult significantly increases the risk of cancer development. PMID- 3332660 TI - Mechanisms of tumour cell metastasis. AB - Abercrombie and his colleagues have accumulated evidence that changes in the heterotypic contact-inhibition response are largely responsible for the invasiveness of cells, at least in culture. We have identified a 37,000 Mr protein on the surface of mouse fibrosarcoma cells that is involved in their in vitro invasion. Blocking this protein with specific antibodies inhibits the invasion of chicken heart fibroblasts by the tumour cells and normal heterotypic contact inhibition is restored. These results are presented in the general framework of metastatic mechanisms and we review a selection of more recent studies aimed at describing the metastatic phenotype in molecular terms. PMID- 3332661 TI - Adhesion plaques: sites of transmembrane interaction between the extracellular matrix and the actin cytoskeleton. AB - In this paper we review what is known about the organization of adhesion plaques, the regions where cells in culture adhere most tightly to the underlying substratum. These specialized areas of the plasma membrane serve as attachment sites for stress fibres. A major objective has been to determine how microfilament bundles are anchored at such regions. In their morphology and composition adhesion plaques resemble the adhesions fibroblasts make to the extracellular matrix. Some extracellular matrix components have been identified on the outside face of adhesion plaques. Within the plasma membrane of adhesion plaques, extracellular matrix receptors, such as the fibronectin receptor (integrin), have been identified. This transmembrane glycoprotein complex has been shown to bind the cytoplasmic protein talin, which, in turn, associates with vinculin. These proteins establish a transmembrane chain of attachment between the extracellular matrix and the cytoskeleton, although how the actin filaments interact with these components remains to be determined. Besides having a structural function, adhesion plaques may also be regions where regulatory signals are transmitted across the membrane. Consistent with this idea has been the finding that various tyrosine kinases and a calcium-dependent protease are concentrated at the cytoplasmic aspect of adhesion plaques. Furthermore, several adhesion plaque proteins become phosphorylated during cell transformation by Rous sarcoma virus. In future work it will be important to determine how such modifications affect the interactions of these proteins and the stability of adhesion plaques. PMID- 3332662 TI - Integrin, a transmembrane glycoprotein complex mediating cell-substratum adhesion. AB - A monoclonal antibody, CSAT, which inhibits the adhesion of chick cells to substrata coated with fibronectin, laminin and vitronectin, has been used to identify a cell surface receptor required for cell-substratum adhesion. This receptor, termed integrin, is found on the ventral surface of cells in close contact adhesion sites, at the periphery of adhesion plaques and beneath stress fibres. It is a heterodimer consisting of non-covalently linked alpha and beta subunits. Integrin binds directly to laminin, fibronectin and vitronectin with dissociation constants in the micromolar range. The binding of integrin to matrix molecules is sensitive to peptides carrying the cell-binding sequence Arg-Gly-Asp and requires heteromeric integrity. Integrin also binds directly to the cytoskeleton-associated protein talin. Thus, integrin has the properties of a transmembrane molecule capable of bringing extracellular matrix and cytoskeleton associated molecules in proper juxtaposition to form adhesion structures. The integrin beta subunit is phosphorylated following Rous sarcoma virus transformation. Phosphorylation alters the ability of the receptor to bind extracellular matrix molecules as well as talin, suggesting a mechanism for the alteration of cellular adhesive and morphological properties following malignant transformation. A major phosphorylation site is on the cytoplasmic domain of the beta subunit. Synthetic peptides homologous with this region of integrin inhibit integrin-talin binding. The gene for the beta subunit of integrin has been sequenced. Its structure is consistent with the membrane-spanning properties of the receptor. Integrin is structurally and serologically related to adhesion receptors from mammalian tumour cells, fibroblasts, platelets and lymphocytes. It appears to be a member of a supergene family of receptors involved in cellular adhesive interactions. Antibody and peptide inhibition experiments have suggested a role for integrin and integrin-like molecules in cell migration, neurite extension, neural differentiation, histogenesis and embryonic development in Drosophila. Thus, integrin appears representative of a set of evolutionarily conserved, biologically important adhesive molecules. PMID- 3332663 TI - Adhesive interactions and the metabolic activity of hepatocytes. AB - The nature and influence of adhesive interactions of rat hepatocytes with components of the extracellular matrix has been studied in culture. Hepatocytes interact with different kinetics to substrata composed of collagen type IV, laminin or fibronectin and adopt significantly different morphologies. The receptors mediating these various responses appear to be specific, according to the matrix, and in the case of fibronectin are complex, implicating several components of the hepatocyte surface. Collagen type IV maintains a differentiated phenotype more efficiently than fibronectin or laminin as measured by the production of adult hepatocyte markers such as albumin and repression of alpha foetoprotein synthesis. Formation of matrix components is also influenced by the substratum: synthesis and secretion of fibronectin or collagen type IV is down regulated when cells are cultured on the homologous substratum. Hepatocytes cultured in vitro secrete components of the coagulation cascade and also mediate fibrinolysis on addition of exogenous plasmin. The results are discussed in relation to the normal phenotype of the mature hepatocyte in vivo. PMID- 3332664 TI - The role of changes in cell shape and contacts in the regulation of cytoskeleton expression during differentiation. AB - As a model for investigating gene regulation in relation to cell and tissue morphogenesis, we studied the expression of the adherens junction proteins, vinculin, alpha-actinin and actin, and that of desmosomal junctions containing the desmoplakin-cytokeratin complex, in response to changes in cell contacts and configuration. In monolayer or suspension cultures of kidney epithelial cells we found high levels of synthesis of cytokeratin and desmoplakin where extensive cell-cell contacts were established. In contrast, cells in sparse monolayers had high levels of the vimentin-type intermediate filaments, but very low levels of cytokeratins and desmoplakin I. Whereas in kidney epithelial cells all cytokeratins were coordinately regulated in response to changes in culture conditions, in mammary epithelial cells a new 45 X 10(3) Mr cytokeratin was induced in dense monolayer and suspension cultures. By treating cells with TPA, intercellular junctions were rapidly disrupted and expression of cytokeratin and desmoplakin was dramatically reduced; however, vimentin expression was not affected. In mammary epithelial cells only synthesis of the 45 X 10(3) Mr cytokeratin was reduced in TPA-treated cells. Thus the synthesis of the cytokeratin-desmoplakin complex was coordinately regulated in response to changes in cell-cell contact and cell shape in a way that is compatible with the organization of these cells in vivo. The relationship between the organization and expression of adherens junction proteins and their role in the acquisition of the differentiated phenotype was studied in fibroblasts and in differentiating ovarian granulosa cells. The synthesis of vinculin in cultured fibroblasts increased dramatically when the cell culture density was high, concomitant with the establishment of extensive cell-substratum and cell-cell contacts of the adherens type. When fibroblasts were plated on substrata of varying adhesiveness, to modulate cell shape from a flat and well-spread to a poorly adherent spherical shape, there was a relationship between vinculin organization and expression: vinculin synthesis decreased dramatically in round cells. The differentiation of freshly isolated ovarian granulosa cells (as measured by production of high levels of progesterone) in response to gonadotropic hormones was followed by dramatic changes in cell shape and organization and expression of adherens junction proteins. Cell shape changed from a flat fibroblastic type to a spherical one, with a reduction in vinculin-containing plaques and the disappearance of actin-containing stress fibres.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332665 TI - The influence of extracellular matrix on gene expression: is structure the message? AB - The study of the regulation of gene expression in cultured cells, particularly in epithelial cells, has been both hampered and facilitated by the loss of function that accompanies culture on traditional plastic substrata. Initially, investigations of differentiated function were thwarted by the inadequacy of tissue culture methods developed to support growth of mesenchymal cells. However, with the recognition that the unit of function in higher organisms is larger than the cell itself, and that gene expression is dependent upon cell interactions with hormones, substrata and other cells, came the understanding that the epithelial cell phenotype is profoundly influenced by the extracellular environment. In the last decade research on epithelial cells has centred on culture conditions that recreate the appropriate environment for function with very promising and important results. The investigations into the modulation of phenotype in culture produced not only a better model, but also contributed to a better understanding of the regulation of normal function. Using cultured mammary gland epithelial cells as a primary model of these interactions, our studies of gene expression are based on three premises. (1) That the extracellular matrix (ECM) on which the cells sit is an extension of the cells and an active participant in the regulation of cellular function; i.e. the ECM is an 'informational' entity in the sense that it receives, imparts and integrates structural and functional signals. (2) That ECM-induced functional differentiation in the mammary gland is mediated through changes in cell shape, i.e. that the structure is in large part 'the message' required to maintain differentiated gene expression. (3) That the unit of function includes the cell plus its extracellular matrix; in a larger context, the unit is the organ itself. These tenets and the data presented below are consistent with a model of 'Dynamic Reciprocity', where the ECM is postulated to exert an influence on gene expression via transmembrane proteins and cytoskeletal components. In turn, cytoskeletal association with polyribosomes affects mRNA stability and rates of protein synthesis, while its interaction with the nuclear matrix could affect mRNA processing and, possibly, rates of transcription. PMID- 3332666 TI - Epithelial cell polarization in culture: orientation of cell polarity and expression of specific functions, studied with cultured thyroid cells. AB - Isolated porcine thyroid cells reorganize in culture into various types of multicellular structure, which differ in the orientation of cell polarity and in the surface of the cell layer accessible to molecules present in the culture medium. The types of structure are: (1) follicles: the basal pole is oriented toward the medium; (2) inside-out follicles or monolayers: the apical pole is facing the culture medium; (3) monolayers on a permeable substratum: both sides of the cell layer are accessible to the medium. Follicles can be transformed into inside-out follicles or monolayers and vice versa by manipulation of the external cell environment and without dissociating the cells. Cells concentrate iodide and respond to acute stimulation by thyroid-stimulating hormone (TSH) when the basal pole is accessible, and organification occurs only when cells form a closed follicular lumen. In porous-bottomed culture chambers monolayers are formed with the basal surface accessible to the medium and the apical compartment separated from the medium. Under these conditions 85-95% of the thyroglobulin produced is secreted apically and 5-15% basally. Thyrotropin stimulates (X3) apical accumulation without modifying secretion in the basal compartment. Sodium transport across the cell layer has been characterized. An amiloride-sensitive influx occurs at the apical pole whereas the Na+/K+-ATPase, localized in the basolateral membrane, mediates ouabain-sensitive efflux at the basal pole. The thyroid epithelium in culture appears therefore as a Na+-absorbing epithelium. The role of this transport in the stabilization of cell polarity is discussed. PMID- 3332667 TI - Novel methods for the guidance and monitoring of single cells and simple networks in culture. AB - The effects of the topography, adhesiveness and chemistry of surfaces in modulating the behaviour of cells in vivo and in vitro have been extensively researched. However, few natural systems are simple enough to allow straightforward conclusions to be drawn, as many different cues are likely to be present at one time. Microelectronic fabrication, normally employed in making integrated circuits, can produce substrates patterned on scales highly relevant to studies of cell behaviour. In this paper, we describe progress in fabricating simple artificial substrata both at the micrometre and sub-micrometre scales. The former can be considered as models for contact guidance along other cells or axonal processes: the latter, models for guidance along aligned collagen matrices. We have systematically studied the reactions of different cell types to simple cues (steps and grooves). Additionally, it may be possible to produce fine resolution patterns with differential adhesiveness, or with other cell-specific surface-chemical properties, such as the differential deposition of proteins, e.g. cell adhesion molecules. We also describe early results in using topographic and other cues to guide cells onto patterned metal electrodes, forming simple electrically active networks of controlled design, from which long-term recordings can conveniently be made. PMID- 3332668 TI - Isolation of morphologically intact mitochondrial nucleoids from the yeast, Saccharomyces cerevisiae. AB - Mitochondrial nucleoids (mt-nucleoids) of the yeast, Saccharomyces cerevisiae, were isolated from spheroplasts of stationary phase cells and their structure and organization were investigated by fluorescence microscopy, electron microscopy, and biochemical techniques. Isolated mt-nucleoids were spherical or ovoid and 0.3 0.6 micron in diameter, and were about the same size and shape as those observed in the cell by the DAPI staining technique. Measurement of DNA content of mt nucleoids, using a video-intensified microscope system, after DAPI staining revealed that a mt-nucleoid in spheroplasts from stationary phase cells contains, on average, 3.9 mtDNA molecules and an isolated mt-nucleoid contains, on average, 3.1. Negatively stained electron micrographs showed that mt-nucleoids consist of particles 20-50 nm in diameter. SDS-polyacrylamide gel electrophoresis of mt nucleoids detected 20 species of polypeptides in the molecular weight range from 10 X 10(3) to 70 X 10(3). Acid-urea/SDS two-dimensional electrophoresis of acid extract from mt-nucleoids indicated that a polypeptide of 20 X 10(3) is the only major polypeptide with basic property like histones. PMID- 3332669 TI - Characterization of antibodies as probes for structural and biochemical studies of tektins from ciliary and flagellar microtubules. AB - Rabbit antibodies raised and purified against three tektins, proteins of flagellar doublet microtubules from sea-urchin sperm (Lytechinus pictus and Strongylocentrotus purpuratus), were used to study tektin biochemistry and their structural localization. Doublet microtubules were fractionated into tektin filaments and separated by SDS-PAGE into three major tektin polypeptide bands (Mr = 47, 51 and 55 (X 10(3)), which were used to immunize rabbits. Antibodies against each tektin (anti-tektins) were affinity-purified and then characterized by two-dimensional isoelectric focusing/SDS-PAGE immunoblotting and by immunofluorescence microscopy. In two-dimensional immunoblots of 0.5% Sarkosyl resistant fractions of flagellar microtubules, the antibody against the 55 X 10(3) Mr tektin (anti-55) stained one major polypeptide of 55 X 10(3) Mr and pI 6.9, anti-51 stained two polypeptides of 51 X 10(3) Mr and pI approximately 6.15, and anti-47 stained one major polypeptide of 47 X 10(3) Mr and pI 6.15. The anti tektins also stained several minor neighbouring polypeptides, which may be isoelectric variants, novel tektins or unrelated proteins. Furthermore, anti-47 crossreacted with the major 55 X 10(3) Mr polypeptide. By immunofluorescence microscopy all three anti-tektins stained methanol-fixed echinoderm sperm flagella and embryonic cilia. In addition, anti-47 and anti-55 stained unfixed, demembranated axonemes. Besides staining axonemes, all anti-tektins labelled the basal body region, and anti-51 labelled the sperm head envelope. These results indicate that the tektins are a complex family of proteins that are components of axonemal microtubules and possibly other cytoplasmic and nuclear structures. PMID- 3332671 TI - Expression of an endogenous galactose-binding lectin in the early chick embryo. AB - The gastrulating chick blastoderm contains lectin activity specific for beta-D galactoside groups. The galactose-binding lectin isolated by affinity chromatography on rho-aminophenyl-beta-D-lactoside separates into two bands when studied by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. One of these LII has a relative molecular mass of 70 (+/- 2) X 10(3) while the other LI is a polypeptide that migrates with the dye front in 10% gels. We have prepared an antiserum against this lectin preparation and have affinity-purified antibodies against LI. When embryos at stages 3-7 were examined by immunofluorescence using the affinity-purified antibodies, lectin was expressed in cells at the lowest portions of the primitive streak as well as in cells migrating laterally from this region to form the endoderm. Lectin was also expressed by the cells of the extra-embryonic endoderm and the primordial germ cells of the proximal area opaca. In transfers of gradient gels stained with affinity-purified antibodies against LI, this lectin had an approximate molecular weight of 6.5 X 10(3). Our results indicate that this lectin is expressed in areas that are undergoing cell spreading. PMID- 3332670 TI - Intermediate filament formation after transfection with modified hamster vimentin and desmin genes. AB - Previously we cloned and characterized the hamster intermediate filament genes coding for vimentin and desmin. It was demonstrated that the cloned desmin gene was expressed after gene transfer and that the newly synthesized protein assembles into intermediate filaments. Here we present data on the transfection of modified vimentin and desmin genes onto simian virus 40-transformed hamster lens cells and HeLa cells. Modifications included: (1) removal of exons encoding the desmin COOH-terminal domain; (2) exchange of exons encoding the COOH-terminal domain of vimentin and desmin; and (3) deletion of part of exon I of desmin, coding for the NH2-terminal amino acids 4-148. In transient transfection assays it was shown that the modifications in the COOH region had no detectable effects on the filament forming potential of the encoded proteins as demonstrated with desmin antibodies in the indirect immunofluorescence test. On the other hand, deletion of a considerable part of the first exon of the desmin gene results in a lack of bona fide intermediate filament formation. Immunoblotting with desmin antibodies of cell populations enriched for the transfected modified genes showed that the presence of the modified genes results in the synthesis of the corresponding proteins with the expected molecular weights. From our results we conclude that in vivo: (1) the presence of the COOH terminus is not essential for filament formation; (2) that an exchange of COOH-terminal parts of vimentin and desmin does not prevent assembly into intermediate filaments; and (3) that removal of the NH2 terminus of desmin affects intermediate filament formation. PMID- 3332672 TI - Evidence for heterogeneity in the 160/165 x 10(3) Mr glycoprotein components of desmosomes. AB - We have prepared both monoclonal and polyclonal antibody preparations directed against the 160/165 x 10(3) Mr glycoproteins (desmogleins) of bovine tongue epithelial desmosomes. The polyclonal antibody preparation recognizes desmosomes in a number of mouse tissues, e.g. mouse skin, heart, bladder and trachea, as determined by immunofluorescence microscopy. Furthermore, the polyclonal antibodies recognize polypeptide(s), present in the high salt, Triton-insoluble residues ('cytoskeleton preparations') of mouse skin, heart, bladder and trachea, which comigrate with the 160/165 x 10(3) Mr glycoproteins of bovine tongue epithelial desmosomes as determined by 'Western' immunoblotting. Conversely, the monoclonal 160/165 x 10(3) Mr antibody preparation recognizes desmosomes of stratified squamous epithelial tissues but not desmosomes in other tissue types. Moreover, whereas the monoclonal antibodies recognize 160/165 x 10(3) Mr polypeptides in mouse skin cell cytoskeletons they show no immunoreactivity with the cytoskeleton preparations of mouse bladder, trachea and heart following immunoblotting. These results suggest therefore that although there are conserved epitopes of the 160/165 x 10(3) Mr glycoproteins there are also epitopes of these molecules which vary from tissue to tissue. Double label immunofluorescence observations of cryostat sections of mouse skin using the monoclonal antibodies and antibodies directed against desmoplakin, a plaque component of desmosomes, reveal that the monoclonal antibodies do not recognize certain desmosomes in basal cells which are recognized by desmoplakin antibodies. Indeed, double label observations of cryostat sections of mouse skin using the monoclonal antibodies and human autoantibodies which react with hemidesmosomal components suggest that the monoclonal antibodies stain desmosomes located along the apical surfaces of basal cells but fail to recognize desmosomes along the lateral surfaces of these same cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332673 TI - Contact behaviour during the reassociation of dissociated epithelial cells in primary culture. AB - The behaviour in culture of dissociated epithelial cells from chick embryo pigmented retina epithelium (PRE), corneal epithelium (CE) and epidermis has been studied using time-lapse cinematography. The analysis concentrated on the contact behaviour of 60 previously isolated cells of each type during a 24 h period starting 3.5 h after the cells were plated out. During the period analysed the number of isolated cells in cultures of all three types gradually decreased as they became incorporated into islands and sheets of cells. However, there were significant differences in behaviour between the cell types during the establishment of these sheets and islands. In PRE cell cultures, islands of cells developed because, throughout the period of analysis, collisions involving previously isolated cells almost invariably resulted in the development of a stable contact. Once having established contact with another cell these cells rarely broke away again to become reisolated. In contrast the contacts formed between colliding CE and epidermal cells were, at least initially, much less stable and cells of both these types were frequently seen to break away and become reisolated after colliding with other cells. Sheets and islands of cells eventually developed in these cultures because the frequency with which isolated cells become reisolated decreased with increasing time in culture. The possible reasons underlying the different behaviour of PRE cells, when compared with that of CE and epidermal cells, are discussed. It is suggested that the decreasing tendency of isolated CE and epidermal cells to become reisolated may be related to the formation of desmosomes. PMID- 3332674 TI - Serological evidence for a defect in RT1.B (I-A) expression by the BDIX rat strain. AB - Astrocytes, astrocytic cell lines and endothelium from BDIX rats were stimulated with recombinant interferon-gamma (IFN-gamma) and the expression of MHC molecules quantified using an enzyme immunoassay (EIA). Using the two mouse anti-RT1.B monoclonal antibodies MRC OX4 and OX6, previously described as recognizing a monomorphic determinant on RT1.B, as well as polyvalent rabbit anti-rat class II antisera, we were unable to demonstrate any induction of RT1.B molecules on these cells under conditions that induced RT1.B expression in all other strains tested. In contrast, RT1.D locus class II molecules, detectable by the antibody MRC OX17, are more strongly expressed in BDIX than in other strains. In experiments using BDIX lymphocytes, this serologically detected defect in RT.1B expression was confirmed using four additional mouse anti-mouse I-Ak monoclonal antibodies, which cross-reacted on all rat strains tested except BDIX. It appears likely that BDIX rats lack either a structural or controlling gene required for RT1.B expression. PMID- 3332675 TI - Combination therapy for dendritic keratitis with acyclovir and vidarabine. AB - We treated 32 patients with dendritic keratitis with a combination of acyclovir 3% ointment and vidarabine 3% ointment or acyclovir and placebo. Patients with acyclovir alone healed in an average time of 7.7 days, while patients on the combination healed in an average of 6 days. Only one patient in the acyclovir and vidarabine group had a healing time longer than 7 days, whereas six patients in the acyclovir and placebo group had healing times longer than 7 days. By the median test, this difference in healing times was statistically significant (p = 0.035), and the combination prevented cases of prolonged ulceration. PMID- 3332676 TI - Light-induced avian glaucoma as an animal model for human primary glaucoma. AB - Glaucoma can be induced in domestic chicks at the will of the investigator, by the simple device of rearing the chicks under continuous light. This light induced avian glaucoma (LIAG) is presented as an animal model system for human open-angle glaucoma. A number of morphological and physiological findings in LIAG are reviewed, and the LIAG system is compared with several other glaucoma model systems, in dogs, rabbits and monkeys. Intraocular pressure in LIAG has been demonstrated to be responsive to several anti-glaucoma drugs, and the system could be used for further drug testing. Thus it is suggested that LIAG may be especially useful in studies seeking to understand human glaucoma, and how to forestall it, or treat it. As well, a prolonged "pre-glaucoma" period is available to the investigator working with LIAG, during which a pathological course is already underway in the eye, but intraocular pressure has not yet gone up. PMID- 3332677 TI - The disposition of bunolol in the rabbit eye. AB - Following topical administration to albino rabbits, bunolol hydrochloride, a beta 1- and beta 2-adrenoceptor antagonist, was rapidly absorbed and distributed in ocular tissues, and transformed intraocularly to a single metabolite, dihydrobunolol. The half-life of bunolol was approximately 1.26 hours in the aqueous humor and 1.63 hours in the ciliary body. There was no significant accumulation of bunolol during a four-day period of twice-daily dosing. Most of the drug was excreted in the urine following ocular or intravenous administration. PMID- 3332678 TI - Topical benzyl alcohol reduces cataract surgery need: two long-term double blind studies. AB - Substances derived from biotransformation of non-steroid antiinflammatory drugs (NSAID) produced by patients responsive to the biological liquid oxidant activity (BLOA) test, have been shown to have anticataract activity. They are all aromatic alcohols with physico-chemical properties similar to benzyl alcohols (BA); they were very efficacious in preventing in vitro (cyanate, heat) cataracts and in vivo (uveitis, radiation, selenite) cataracts but had no effect on sugar cataracts. The mechanism underlying this effect seems to be mainly antioxidant together with a stabilizing effect on lens membrane integrity and a stimulating effect on Na-K ATPase and membrane sodium pump. The well balanced lipo- and hydro solubility of these compounds makes them very suitable for topical application to the eye as lipid solubility is the major factor governing transcorneal penetration of drugs. In the two long-term double blind studies on humans described here, comparing BA, placebo and Catalin in the topical treatment of progressive cataract rapid (2-3 weeks treatment) reversal of incipient cataract was obtained accompanied by a marked improvement of vision and by a significantly lower percentage of eyes requiring surgery after 22 months treatment with BA than with placebo and Catalin. In conclusion, further studies on the effect on the eye of BA and similar compounds such as phenyl-ethanol are advisable especially because they are already used as preservatives in eye-drop formulations. PMID- 3332679 TI - Intravitreal ceftazidime in a rabbit model: dose- and time-dependent toxicity and pharmacokinetic analysis. AB - We delineated the dose-and time-dependent retinal toxicity of intravitreal ceftazidime using electroretinography (ERG) in phakic rabbit eyes. Toxicity was evaluated following intravitreal doses ranging from 0.5 to 50 mg/0.1 ml. Eyes were examined prior to injection, at one day, and at seven days after injection. ERG patterns at one and seven days indicated a toxic response to doses of 20 to 50 mg. Doses of 10 mg or less gave a transient depression of the B-wave at one day, but a return to normal was observed at the seven-day evaluation. Pharmacokinetic analysis following intravitreal injection of 2 mg of ceftazidime into uninfected phakic rabbit eyes disclosed vitreous levels of: 1711 micrograms/ml at 0 hr; 1340 micrograms/ml at 8 hr; 451 micrograms/ml at 24 hr; 270 micrograms/ml at 48 hr and 67 micrograms/ml at 72 hr. Peak aqueous humor level was 139 micrograms/ml 8 hr post-injection. Potentially therapeutic drug levels were obtained in the aqueous and vitreous humors following a nontoxic intravitreal dose of ceftazidime in a rabbit model. PMID- 3332680 TI - Growth factor effects on corneal wound healing. AB - Corneal wound healing and the many factors which may promote or prevent it are of concern to both clinicians and researchers. Ophthalmologists are often confronted with corneal dystrophies and problematic injuries resulting in persistent and recurrent epithelial erosion and with permanent endothelial loss. Scientists have long noted that corneal epithelial and endothelial cell layers are among the most simple and accessible for experimental manipulation and non-invasive study in both animal and human models. Healing epithelium provides a classical model of cell locomotion over a surface, while endothelial cell viability and function is of fundamental importance to maintenance of corneal clarity and vision during the aging process as well as after disease, surgery, or laser treatment. Growth factors can now be produced homogeneously by genetic engineering, increasing the potential of commercial development for purposes such as corneal wound healing. This article reviews some known properties of growth factors whose effects have been at least partially characterized in corneal tissues. PMID- 3332681 TI - Ganglioside administration in retinitis pigmentosa. AB - The retinitis pigmentosa process typically causes variably progressive visual loss due to retinal photoreceptor and pigment epithelial cell deterioration. No effective agent either to retard or stop the deterioration has been known. Because gangliosides have been shown to have a variety of trophic effects on peripheral nervous tissue, we administered a daily 40 mg intramuscular dose in a prospective, double-blind, randomized, placebo-controlled trial in 30 persons with retinitis pigmentosa with or without congenital deafness. When we compared baseline performance on the two principal study outcomes, visual field area and electroretinographic response amplitudes, there was a marginally statistically significant increase in visual field area in the ganglioside-treated group. The subgroup of subjects who had recordable electroretinograms at baseline and who received the drug showed in three of five cases an increase in amplitude to all stimuli. These results appear encouraging; however, the data must be interpreted cautiously because the numbers of individuals are very small. Further study of the possible benefits of ganglioside administration to retinitis pigmentosa patients appears warranted. PMID- 3332682 TI - Central control of intraocular pressure. PMID- 3332683 TI - Isolation of genes required for hydrogenase synthesis in Escherichia coli. AB - A mutant strain of Escherichia coli, strain AK23, is devoid of hydrogenase activity when grown anaerobically on glucose and cannot grow on H2 plus fumarate. From E. coli chromosomal DNA library, a plasmid, pAK23, was isolated which restored hydrogenase activity in this strain. Two smaller plasmids, pAK23C and pAK23S, containing different parts of the insert DNA fragment of plasmid pAK23, were isolated. The former plasmid restored activity in strain AK23 while the latter did not. The smallest active DNA fragment in plasmid pAK23C was 0.9 kb. This gene is designated hydE. Plasmids pAK23 and pAK23S restored activity in another hydrogenase-negative strain, SE-3-1 (hydB), while plasmid pAK23C did not, suggesting that plasmid pAK23 contains two genes required for hydrogenase expression. Strain AK23 was also devoid of formate hydrogenlyase and formate dehydrogenase activities and these activities were restored by some of the plasmids. Hydrogenase and formate-related activities in strain AK23 were restored by growth of cells in a high concentration of nickel. Plasmid pAK23C led to synthesis of a polypeptide of subunit molecular mass 36 kDa and plasmid pAK23S led to synthesis of polypeptides of subunit molecular masses 30 and 41 kDa. PMID- 3332684 TI - Mannoprotein of the yeast cell wall as primary receptor for the killer toxin of Saccharomyces cerevisiae strain 28. AB - The killer toxin KT 28 of Saccharomyces cerevisiae strain 28 is primarily bound to the mannoprotein of the cell wall of sensitive yeasts. The mannoprotein of S. cerevisiae X 2180 was purified; gel filtration and SDS-PAGE indicated an estimated Mr of 185,000. The ability to bind killer toxin KT 28 increased during purification of the mannoprotein. Removing the protein part of the mannoprotein by enzymic digestion or removing the alkali-labile oligosaccharide chains by beta elimination did not destroy the ability to bind killer toxin KT 28. However, binding activity was lost when the 1,6-alpha-linkages of the outer carbohydrate backbone were hydrolysed by acetolysis. The separated oligomannosides of the side chains also failed to bind toxin, indicating that the main mannoside chains were essential for the receptor activity. The reversible adsorption of killer toxin to mannoprotein was demonstrated by linking it covalently to Sepharose and using this material for affinity chromatography. A 90-fold increase in the specific activity of a preparation of killer toxin KT 28 was achieved in this way. PMID- 3332685 TI - Tubulin and actin topology during zygote formation of Saccharomyces cerevisiae. AB - The topology of tubulin and actin during mating of Saccharomyces cerevisiae was analysed by fluorescence microscopy with the monoclonal anti-tubulin antibody Tu01 and rhodamine-labelled phalloidin. Preconjugatory cells displayed an asymmetric distribution of the microtubule and actin cytoskeleton and an overall polarization of the cells preceding cell fusion. Prior to karyogamy, the haploid spindle pole bodies were associated with abundant cytoplasmic microtubules. Budding zygotes revealed the same tubulin and actin patterns as vegetative cells. Treatment of the mating mixture with the microtubule inhibitor nocodazole (10 micrograms ml-1) did not prevent polarization and fusion of haploids, zygote formation and emergence of the first zygotic bud. In marked contrast, the migration of the nucleus in preconjugatory cells as well as nuclear migration and fusion within the zygotes was unequivocally blocked by the action of the drug. It is suggested that the problem of the morphogenesis of mating should be approached by considering interactions at the cell periphery. PMID- 3332686 TI - Highly efficient uptake of a rifamycin derivative via the FhuA-TonB-dependent uptake route in Escherichia coli. AB - Rifamycin CGP 4832 is a semisynthetic rifamycin derivative. It is at least 200 times more active than rifampicin against Escherichia coli and related bacteria. This increased activity is shown here to be due to the efficient uptake of CGP 4832 across the E. coli outer membrane via the ferrichrome transport system comprising the outer membrane FhuA (TonA) protein, the ferrichrome receptor, and the inner membrane TonB protein. CGP 4832 competed with ferrichrome and other iron siderophore complexes, and with bacteriophage T5 and colicin M for binding sites on the FhuA protein. Mutations in fhuA or tonB genes reduce CGP 4832 sensitivity to a level comparable to that to rifampicin. There is no evidence that CGP 4832 or rifampicin utilize the inner membrane ferrichrome transport system to gain entry into the cytoplasm. PMID- 3332687 TI - Ultrastructure of Saccharomyces cerevisiae cells accumulating Golgi organelles. AB - Restrictive phenotype of sec 7 mutant of Saccharomyces cerevisiae was examined by freezefracture electron microscopy. In accordance with previous findings (NOVICK et al. 1981) dictyosomes and middle-size (200-600 nm) vesicles (Berkeley bodies) were found to accumulate. Dictyosomes are formed by aggregated flattened or dilated cisternae without associated secretory vesicles. After transfer to permissive conditions the dictyosomes disappear and are not detectable, just like in the wild type or in the permissive phenotype. Associated with the restrictive phenotype is an extended plasma membrane and tonoplasts with particle-free impressions. PMID- 3332688 TI - Glial repair in an insect. AB - The repair of cockroach central nervous connectives, following selective glial disruption, involves an initial invasion of the lesion by a novel cell class. The available evidence, including that obtained using monoclonal antibodies, shows that these cells arise from circulating haemocytes. These invasive exogenous cells are restricted to the lesion zone. They are not only involved in initial repair of the peripheral glial elements, but may also be responsible for initiating recruitment and division of endogenous reactive cells. There is a clear anterior polarity in this recruitment, with significantly higher numbers of cells appearing anterior to, and then within, the lesion area. Characteristically, recognizable exogenous cells decline in number after 3 days, although there is no overall reduction in cell numbers within the lesion at this stage, nor has significant cell division begun. This suggests that the haemocyte derived cells transform into, or are replaced by, functional perineurial glia, between 3 and 5 days, coincident with the restoration of the blood-brain barrier and the onset of endogenous cell division. Glial repair in the insect CNS can thus be divided into three phases which show striking similarities to the repair sequence in vertebrate brain. These include: an initial invasion of the lesion by exogenous cells, subsequent glial proliferation and then longer term fluxes in cell numbers and distribution. PMID- 3332689 TI - In vitro studies on the control of nerve fiber growth by the extracellular matrix of the nervous system. AB - 1. Cultured neurons from embryonic chick sympathetic ganglia or dorsal root ganglia grow nerve fibers extensively on simple substrata containing fibronectin, collagens (types I, III, IV), and especially laminin. 2. The same neurons cultured on substrata containing glycosaminoglycans grow poorly. Glycosaminoglycans (heparin) inhibit nerve fiber growth on fibronectin substrata. 3. Proteolytic fragments of fibronectin support nerve fiber growth only when the cell attachment region is intact. For example, a 105 kD fragment, encompassing the cell attachment region, supports growth when immobilized in a substratum, but a 93 kD subfragment, lacking the cell attachment region, is unable to support fiber growth. When it is added to the culture medium, the 105 kD fragment inhibits fiber growth on substrata containing native fibronectin. 4. In culture medium lacking NGF, DRG neurons extend nerve fibers only on laminin and not on fibronectin, collagen or polylysine. Studies with radioiodinated laminin indicate that laminin binds with a relatively high affinity (kd approximately equal to 10( 9) M) to DRG neurons, and to a variety of other neural cells (NG108 cells, PC12 cells, rat astrocytes, chick optic lobe cells). We have isolated a membrane protein (67 kD) by affinity chromatography on laminin columns and are characterizing this putative laminin receptor. 5. Dissociated DRG neurons or ganglionic explants cultured on complex substrata consisting of tissue sections of CNS or PNS tissues extend nerve fibers onto the PNS (adult rat sciatic nerve) but not CNS (adult rat optic nerve) substrata. Other tissue substrata which support fiber growth in vivo (embryonic rat spinal cord, goldfish optic nerve) support growth in culture. While substrata from adult CNS, which support meager regeneration in vivo (adult rat spinal cord) support little fiber growth in culture. 6. Ganglionic explants cultured in a narrow space between a section of rat sciatic nerve and optic nerve grow preferentially onto the sciatic nerve suggesting that diffusible growth factors are not responsible for the differential growth on the two types of tissues. 7. Dissociated neurons adhere better to sections of sciatic nerve than optic nerve. Laminin, rather than fibronectin or heparan sulfate proteoglycan, is most consistently identifiable by immunocytochemistry in tissues (sciatic nerve, embryonic spinal cord, goldfish optic nerve) which support nerve fiber growth. Taken together, these data suggest that ECM adhesive proteins are important determinants of nerve regeneration. PMID- 3332690 TI - Neuronal expression of mutations affecting primarily glia in the mouse: studies in the dysmyelinated and convulsive mutant quaking. AB - 1. Various aspects of the noradrenergic system in the brain of the dysmyelinating convulsive mutant mice quaking have been examined. 2. Determination of the endogenous contents of noradrenaline and its metabolite 3-methoxy 4-hydroxyphenyl ethyleneglycol (MOPEG), as well as measurement of the electrically-evoked release of (3H)-noradrenaline shows an increased noradrenergic activity in the brain of the mutants, when compared to non convulsive controls of the same strain. 3. Ontogenic development of alpha adrenergic receptors indicate that an increased density of alpha-2 sites precedes the appearance of the first convulsions by approximately one week. 4. Anatomical determination of the number of noradrenergic neuronal cell bodies in the locus coeruleus shows a hyperplasia of this nucleus in the mutants. 5. Electrolytic coagulation of the locus coeruleus inhibits the convulsions of the quaking mice. 6. These results suggest that an alteration of the embryonic differentiation of the locus coeruleus, which gives rise to the majority of brain noradrenergic neurons, provokes a hyperactivity of this neuronal system, thereby triggering the convulsions of the quaking mutant mice. 7. The possible involvement of other neurotransmitter systems in the convulsions of these mutants, together with the nature of the relationship between neuronal abnormalities and dysmyelination phenomenon, are discussed. PMID- 3332691 TI - The glial blood-brain barrier of crustacea and cephalopods: a review. AB - 1. The glial blood-brain barrier of invertebrates is an accessible, polarised glial layer that permits study of glial cells in their normal relations with neurons. Crayfish 2. The glial "perineurium" forms the blood-brain interface in crayfish, and acts as a barrier to horseradish peroxidase (HRP) and ionic lanthanum. By contrast, the perineurium of the peripheral nervous system is relatively permeable. 3. The ionic permeability of the blood-brain interface can be studied in a sucrose gap chamber, using an extra-cellular microelectrode to monitor the potential across the perineurium following changes in the bathing medium. Subtraction of the microelectrode trace from the sucrose gap records gives the change in the axonal membrane potential. 4. Raised [K+] in the bath causes a complex change in perineurial potential, with the initial transient indicating that the outer (basal) glial membrane is highly K+ selective. The axonal response shows that the time constant for K+ uptake (tau u) and efflux (tau E) across the perineurium of the order of 3-4 min, but the interstitial [K+] in the steady state, [K+] infinity is always less than in the bathing medium. The results are explained by a model incorporating a K+ sink, which may be glial. 5. Strophanthidin and ethacrynic acid have little effect on tau u or K infinity, but cause a rise of tau E. Cold temperature pulses causes changes in the perineurial potential compatible with depolarisation of the inner (apical) membrane. A model is proposed with a Na+-K+-2 Cl co-transporter on the perineurial basal membrane, and an electrogenic Na+-K+-ATPase on the apical.membrane, consistent with results from vertebrate glial/ependymal epithelia. Cephalopods 6. The brain of the cuttlefish Sepia has an extensive system of microvessels. In the vertical and optic lobes studied, a perivascular glial layer forms a barrier to HRP. The occluding structure appears not to be a classical tight junction but may involve condensation of extracellular material. There is no barrier between retinal axons and blood. 7. Studies with radiolabelled polyethylene glycol (PEG4000) and EDTA show that the Sepia blood-brain barrier is as tight as the endothelial barrier of mammals. 8. A modification of the Oldendorf arterial injection technique is used to show that glucose transport at the Sepia barrier is mediated by a Na+ independent hexose carrier resembling that of mammalian red cells and blood-brain barrier. 9. The blood-axon interface fo mantle nerves in the squid Alloteuthis is relatively impermeable to small ions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3332692 TI - In vitro model systems permitting the analysis of the differentiation of mammalian progenitor cells either into neurons or into glial cells. AB - The peripheral nervous system, including both neurons and Schwann cells, is derived almost entirely from the neural crest. We described here the use of the migratory properties of mouse neural crest cells and chemically defined conditions to differentiate them in vitro into neuronal derivatives. PMID- 3332693 TI - An automated technique to measure breakdown products of C3 with C3d specificities by peak-rate nephelometry. PMID- 3332694 TI - An evaluation of a new commercial urine transport system. PMID- 3332696 TI - Immunology: the science and service of the future? PMID- 3332695 TI - Clinical applications of tumour markers. PMID- 3332697 TI - Education in the medical laboratory sciences: the past, and future developments. PMID- 3332698 TI - A short history of the Institute of Medical Laboratory Sciences. PMID- 3332699 TI - [The role of ofloxacin (Tarivid) therapy in respiratory and urinary tract infections]. AB - In this study, 14 patients with urinary tract infection and 8 patients with respiratory tract infection were given 400 mg/day of ofloxacin. 12 of 14 patients with urinary tract infection and 4 of 8 patients with respiratory tract infection was cured and clinically improved. 12 of 13 E. coli isolates were eradicated with this treatment. No severe adverse reactions were observed. No in vitro resistance against ofloxacin was seen. PMID- 3332701 TI - [The isolation, classification and some physiological properties of a protease producing bacterium]. AB - A proteolytic bacterium was isolated from specimen collected from soil. The protease producing bacterium showed optimal growth in media with neutral pH and when incubated at 30 degrees C aerobically. According to the classification results, the gram (+), sporulating bacillus was a Bacillus genus member. Also some physiological properties of the isolated bacterium was determined. PMID- 3332702 TI - [Monoclonal antibodies]. AB - Monoclonal antibodies have the capability to bind specifically to the antigens to which they are targeted, and hybridoma technology makes the production of these antibodies possible. Now, it is used in diagnosis and treatment of various diseases. PMID- 3332700 TI - [The frequency of group A beta-hemolytic Streptococcus in acute tonsillopharyngitis and therapy with cefadroxil, clavulanic acid-amoxicillin combination and erythromycin in patients unresponsive to procaine penicillin therapy]. AB - In January, February and March 1987, the frequency of Group A beta hemolytic streptococcus among 468 patients with acute tonsillopharyngitis who admitted to Dr. Sami Ulus Children's Hospital was % 41. Ten day procaine penicillin therapy was not successful in the % 29.5 patients. Cefadroxil (Duricef), clavulanic acid amoxicillin combination (Augmentin) and erythromycin were tried in these patients. While the success rate of Duricef therapy was % 55, the results of other drug therapies were not been successful. PMID- 3332703 TI - [A comparison of manual methods and enterotube II (Roche) for the identification of gram-negative enteric bacteria isolated from feces]. AB - The Enterotube II and classic manual methods were used in parallel to identify 100 members of the enteric bacteria isolated from feces culture. Among these isolated bacteria Shigella, Salmonella and E. coli were found 34%, 25%, 22% respectively. The Enterotube II and classic manual methods gave the same results for identification of Salmonella and Shigella. The Enterotube II correctly identified 98% of all gram negative enteric bacteria. Other advantages and disadvantages of these methods are discussed in our study. PMID- 3332704 TI - [Susceptibility of some bacteria isolated from clinical samples to third generation cephalosporins]. AB - In this study, we evaluated the susceptibility of some Staph. aureus, Staph. epidermidis, E. coli, Klebsiella, Proteus, Pseudomonas strains to third generation cephalosporins in-vitro by disk diffusion technique which are in use in Turkey. These bacteria isolated from various clinical samples at the bacteriology laboratory in Ibni Sina hospital between January 1986-January 1987. The antibiotics used in this study are ceftizoxime, cefotaxime, ceftriaxone, cefoperazone. According to the results of this study, it can be said that cefotaxime is the most effective third-generation cephalosporin against all these bacteria by testing in-vitro. PMID- 3332705 TI - [A comparison of the in vitro susceptibility of three bacteria to beta-lactamase inhibitors and to ampicillin and cefazolin]. AB - In this study in vitro susceptibility of three different bacteria, which are able to release various Beta-lactamases, against combinations of clavulanic acid + amoxicillin and sulbactam + ampicillin were compared with susceptibility to ampicillin alone and cefazolin of same strains. PMID- 3332706 TI - Molybdenum--an essential trace element. PMID- 3332708 TI - Heterogeneity of cholesterol homeostasis in humans. PMID- 3332707 TI - Breast-feeding trends among poor and well-to-do mothers in Singapore. PMID- 3332709 TI - Coronary heart disease and linoleic acid content of adipose tissue. PMID- 3332710 TI - The Journal of Biological Chemistry, Volume 203, 1953: Isolation and identification of the xanthine oxidase factor as molybdenum. By Dan A. Richert and W. W. Westerfeld. PMID- 3332711 TI - Mobilization of tissue zinc for growth and reproduction. PMID- 3332712 TI - Dietary regulation of aldolase. PMID- 3332713 TI - Myofascial pain syndrome. AB - Myofascial pain, a general descriptive term, is applied to painful sensations that extend along one or more skeletal muscles and their fascia. Trigger points, discrete hyperesthetic areas within the muscle and its fascia, are characteristically found in myofascial pain. On the other hand, myofascial pain syndrome is a painful condition characterized by the presence of trigger points, local and referred pain, tenderness, referred autonomic phenomena as well as anxiety and depression. Patients affected by myofascial pain, trigger points, or myofascial pain syndrome, represent a significant population group requesting services in the offices of general practitioners, orthopaedic surgeons, and physicians treating musculoskeletal disorders. PMID- 3332714 TI - Calcitonin and osteoporosis. New mechanisms of pathophysiology. PMID- 3332716 TI - Major acetabulum reconstruction using autograft bone in cemented hip arthroplasty. AB - Acetabular wall deficiency is a relatively common problem in prosthetic hip arthroplasty. The authors have reviewed the results of acetabular reconstruction using autogenous bone grafts, either iliac wing or femoral head, in 49 cases in which a cemented acetabular component was employed. Thirty-one were primary cases, 15 revisions, and 3 ankylosed hips. The roof only was deficient in 20, the anterior wall in five, and the posterior wall in one. Fourteen had combined deficiencies and nine had total acetabular deficiency. Follow up ranged from three to eight years. The results have been reasonable with no graft absorption and no early acetabular component loosening. Failure of the femoral side in one case of total acetabular reconstruction at four years led to revision. The bone grafts were found to be united and had re-established a normal blood supply. It is concluded that autogenous bone grafting of the acetabulum is a reasonable procedure. PMID- 3332715 TI - Proximal humeral fractures revisited. AB - Although 80% of proximal humeral fractures can be managed fairly easily, 20% are significantly displaced and difficult to analyze and treat. The four-segment classification of proximal humeral fractures allows the fracture to be understood and described intelligently, provides a guide to treatment, and helps the physician to make early prognostic judgments. Plain radiographs, tomography, and/or CT scanning allows an individual case to be fitted into the classification scheme. Treatment (non-operative or operative) depends on the degree of displacement of the four major segments, whether the humeral articular surface is involved, and whether the glenohumeral joint is dislocated. Follow-up care and rehabilitation are extremely important for an optimum final outcome. PMID- 3332717 TI - Historical vignette #8. General Ulysses S. Grant's hip fracture. AB - Many biographers have discussed the throat cancer that plagued General Ulysses S. Grant toward the end of his life. However, little attention has been focused on his orthopaedic problems. On Christmas Eve in 1883, Grant slipped on an icy walk and fell. Following this accident he was bedridden for weeks and orthopaedically disabled for the remainder of his life. Although biographers have documented this incident, the outcome of the accident has been variously attributed to a sprain, muscle rupture, or simply a lack of exercise. The history of the injury and the nature of the symptoms and disability, which suggest that the General may have sustained a hip fracture, are reviewed with a discussion of the state of hip fracture diagnosis, treatment, and prognosis taken from the textbooks of the period. PMID- 3332719 TI - Current management of brain stem gliomas. AB - Brain stem gliomas constitute 10-20% of central nervous system tumors in children. Management of these tumors remains controversial. In general, the prognosis for long-term survival is poor, but brain stem gliomas represent a heterogeneous population of tumors, some of which have a better prognosis than others. Improvements in diagnostic imaging techniques, particularly the availability of magnetic resonance imaging, provide the means to differentiate among these populations. Advances in radiation therapy may provide the means to improve survival. In this article we review the reported series and the present state of the art for the diagnosis and management of children with brain stem gliomas. PMID- 3332718 TI - Excellence in search of recognition. The continuing struggle over subspecialty certification. PMID- 3332720 TI - Dandy's contributions to the foundation of neurological surgery. PMID- 3332721 TI - [A hand up]. PMID- 3332722 TI - [The Anna Rydlowna Krakow School of Nurses]. PMID- 3332723 TI - The pathogenetic significance of tubular leakage in acute renal failure (vasomotor nephropathy). PMID- 3332724 TI - Acute glomerular thrombosis with CsA treatment. AB - Cyclosporin A (CsA) is used widely as an immunosuppressive in organ transplantation. Although it is highly effective, acute and chronic nephrotoxicity of CsA are of continuing concern. A case of acute glomerular thrombosis secondary to CsA therapy in a renal transplant recipient is described. The course of the accompanying acute renal failure and its reversal following discontinuation of CsA and therapy with intra-arterial streptokinase is outlined. CsA-induced capillary thrombosis is rare but has been described in renal transplant recipients as well as in hepatic and bone marrow transplantation. It may give rise to diagnostic confusion in the early days following renal transplantation, where it may mimic acute rejection. The etiology of CsA-induced glomerular capillary thrombosis remains speculative. PMID- 3332725 TI - Urinary kallikrein excretion in chronic renal failure: relationship to blood pressure and the acute effect of captopril. AB - Previous studies of the renal kallikrein-kinin system in chronic renal failure (CRF) have given conflicting results. We have assessed activity of this vasoactive hormone system in CRF and investigated a possible relationship to hypertension in patients with CRF: 24-hour urinary kallikrein excretion (UKa) was measured in 22 patients with CRF (9 normotensive and 13 hypertensive) and 11 healthy controls. Age, sex, urine volume, and urinary sodium excretion were similar in each group. Compared with controls, UKa was reduced in both normotensive and hypertensive patients with CRF, with no difference between CRF groups. The reduction in UKa in CRF was less than the reduction in glomerular filtration rate (GFR), as assessed by endogenous creatinine clearance (CCr). When UKa was divided by CCr, UKa/mL CCr was therefore increased, to a similar extent, in both normotensive and hypertensive patients with CRF. This suggests that release of renal kallikrein from functioning nephrons is increased in CRF. The results do not support a role for deficient kallikrein release in the genesis of hypertension in CRF, as previously suggested; however, these abnormalities could be relevant to other aspects of renal function in CRF. The converting-enzyme inhibitor, captopril, was given to 5 patients with CRF, hypertension, and low UKa. Introduction of captopril was followed by a further reduction in UKa in all subjects. Captopril is known to inhibit kininase II, the principal enzyme involved in degradation of kinins; this potentiating effect may be counteracted by a reduction in renal kallikrein release and hence in kinin generation. PMID- 3332727 TI - Trachoma research advances. PMID- 3332726 TI - Trachoma research: laboratory and epidemiologic aspects. PMID- 3332728 TI - Endoscopic ultrasonography in the diagnosis of esophageal carcinoma. AB - In selection for esophageal cancer treatment, it is necessary to evaluate the tumor stage. We have used endoscopic ultrasonography (EUS) for diagnosis of the depth of cancer invasion and the presence of lymph node metastasis since 1983. The EUS image of the normal esophageal wall showed 5 layers. In all, 222 cases of esophageal cancer were examined with EUS, and a radical operation was performed on 139. In 78 of those cases, the scope was passed beyond the cancer site, and total observation was achieved (56%). The extent of cancer invasion was correctly determined in these 78 cases (84%). Thoracic lymph nodes that could be detected by EUS were located in the posterior mediastinum and measured more than 3 mm in diameter. Diagnostic criteria for lymph node metastasis were designated as follows: (1) spherical shape, (2) a distinct border, and (3) heterogenous echo spots within the nodes. The above criteria yielded a sensitivity of 87%, a specificity of 90%, and an overall accuracy of 89% according to the histological examination of the removed lymph nodes. PMID- 3332729 TI - Endoscopic ultrasonography of tumours of the oesophagus and the stomach. AB - Endoscopic ultrasonography is one of the intracavitary ultrasound procedures, all of which have as their objectives the attainment - through the use on high frequencies - of high resolution, and the avoidance of disturbing air and bone. In the technique of endoscopic ultrasonography, a high-resolution ultrasonic transducer attached to the tip of an endoscope is introduced into the gastrointestinal tract, from where it becomes possible to represent the wall of the tract, and also its neighbouring organs. The last few years have shown that the procedure is capable, in principle, of meeting the expectations placed in it. PMID- 3332730 TI - Morphological appearance of low-level echoes in the gallbladder. Interpretation with microscopic biliary analysis and clinical correlation. AB - A total of 743 patients affected by various gastrointestinal disorders were examined by ultrasound. The presence in the gallbladder bile of low-level echoes (LLE) was observed in 56 (7.5%). Twenty-six of these patients had surgery: 24 underwent cholecystectomy for important biliary-like painful symptomatology, and 2 had cephalopancreatectomy for pancreatic head carcinoma. Both macro- and microscopic controls of the bile were carried out in all 26 patients. In 20 cases, only microscopic cholesterol crystals and calcium bilirubinate granules were observed in the bile. The microscopic evidence of these crystals was associated in four cases with macroscopic evidence of so-called "biliary sludge" and in four cases with macroscopic evidence of highly viscous bile. In the other 6 cases these crystals were associated with the presence of cholesterol stones. The authors consider that the observation of LLE in the gallbladder bile is an important index of the presence of cholesterol crystals and/or calcium bilirubinate granules. These LLE can assume polymorphic aspects, described by the authors, which may simulate other pathologies and lead to incorrect echographic diagnosis. The high incidence of LLE in an alithiasic population (5.1%), together with the elevated frequency, according to the authors, of association of these echoes with a painful biliary-like symptomatology (52.6%), underlines the diagnostic importance of an accurate ultrasound investigation in this type of pathology. PMID- 3332731 TI - Complications of flexible fiberoptic sigmoidoscopy. A conceptual approach. AB - This paper presents an overview of the potential risks associated with the use of the flexible fiberoptic sigmoidoscope. A reasonable review of the literature on endoscopy reveals few instances of admitted complications. We draw upon a decade of personal observations and experience with over 10,000 examinations to substantiate the actual and potential hazards of flexible fiberoptic sigmoidoscopy. A conceptual approach to recognizing and avoiding the consequences of complications is presented. PMID- 3332732 TI - Viloxazine versus imipramine in the treatment of enuresis. PMID- 3332733 TI - The interaction between human blood-group (ABO) substances and enteropathogenic bacterial agents. PMID- 3332734 TI - Gross and histological characterization of endometrial tissues from SLA miniature pigs with cystic endometrial hyperplasia. AB - Cystic endometrial hyperplasia (CEH) is a uterine disorder characterized by the formation of large numbers of cysts in the endometrium. The purpose of this study was to examine and characterize cell types in the endometrium associated with the cysts and uterine glands. No apparent histological differences between CEH involved and normal uterine columnar epithelium were found. Endometrial glands in CEH-involved and normal uteri were lined with simple or ciliated columnar epithelial cells and surrounded by lamellar connective tissue. The cyst epithelium appeared to be stretched obliquely and compressed so that both the cells and nuclei were horizontally oriented relative to the cyst lumen and were surrounded by lamellar connective tissue. Electron microgaphs revealed an abnormally high number of mitochondria in the cystic cells as compared to normal glandular cells. In conclusion, CEH is characterized by the formation of cysts which develop from the uterine glandular tissue. Epithelial cells lining the glands appeared to be distorted, possibly in response to internal pressure from increased volume due to high metabolic activity, and/or no uterine luminal opening. PMID- 3332735 TI - The hypothalamic magnocellular system in the domestic fowl. Study on semithin sections. AB - Neuronal characteristics and location of the neurosecretory, magnocellular, fuchsin-paraldehyde-positive (FA+) system of the fowl are described at the light microscopic level on serial semithin sections. Three nuclei make up this system, the nucleus supraopticus, n. magnocellularis interstitialis and n. paraventricularis. These nuclei display magnocellular neurons, not showing a parvocellular component. The neurons of the three nuclei showed a scattered pattern of distribution and a dense surrounding neuropil. Groups formed by magnocellular neurons were found in the three nuclei and groups formed by one magnocellular and a parvocellular neurons were only found in the n. magnocellularis interstitialis and in the n. paraventricularis. The presence of neurons in apposition to blood vessels was frequent in the magnocellular FA+ system of the domestic fowl. PMID- 3332737 TI - Fetal blood sampling in twin pregnancies. Prenatal diagnosis and management of 19 cases. AB - Twin pregnancies pose particular problems in both prenatal diagnosis and obstetric management. We present 19 twin pregnancies that underwent fetal blood sampling (FBS). The indications were mostly similar to those for singleton pregnancies, with both fetuses being sampled. There was one indication specific to twin pregnancies; disseminated intravascular coagulation in the retained twin after the death-in-utero (DIU) of the other. In 5 cases, only 1 twin was sampled; in 2 because the second twin was female in the diagnosis of an X-linked disorder; in 1 because of technical failure, and in 2 the other twin had predeceased. Eight pregnancies continued after the FBS delivering 2 live, healthy infants, though 5 were delivered before 37 weeks of gestation. In 7 cases there was a discordance in the diagnosis between the twins. In 3 of these cases the affected fetus underwent selective termination by air embolism; in 2 cases the pregnancies were continued and the affected twin not resuscitated; 1 pregnancy is still in progress, and 1 patient had a non-medically supervised termination of both twins in another country. Two patients miscarried within a week of the FBS. Two patients had only 1 living twin at the time of FBS; 1 had a second DIU a month after the FBS and the other a neonatal death at 11 days of age in an infant with severe porencephaly. FBS is technically feasible for similar indications as for singleton pregnancies though discordance in diagnosis raises specific management problems. PMID- 3332736 TI - Appearance of immunoreactive endocrine cells during the development of the rat pancreas, with special reference to polypeptide-secreting cells. AB - The chronological appearance of PP cells in fetal pancreatic islets was studied using specific anti-PP serum and the direct peroxidase method. The presence of A and B cells was also studied, using the same immunocytochemical technique, as a reference pattern related to data previously reported. Our data confirm that the A cell is the earliest endocrine cell type, appearing on the 12th day of gestation, followed by B cells (14th day) and later on by PP cells (19th day). Primitive islets were identified in the pancreas after the 15th day. However, the spatial cell disposition observed in the adult islet was only recognized at the 20th day of gestation. The data reported provide the necessary information to establish the complete chronology in the rat fetus. Consequently, the development of pancreatic islets in the rat fetus could be employed as a useful model to study the existence of factors that control the sequential appearance of endocrine cells and the possible changes occurring in the islets of animals with genetic diabetes during the fetal period. PMID- 3332738 TI - Intrauterine growth retardation: pathophysiology and possibilities for intrauterine treatment. AB - Advances in obstetrical care have decreased perinatal morbidity and mortality considerably over the past decade. Intrauterine growth retardation (IUGR) comprises an important component of the remaining morbidity and mortality. Through increased understanding of the pathophysiology of the different types of IUGR, we can begin to devise specific therapies for IUGR rather than the empiric ones currently employed. For example, it may become possible to selectively treat certain types of IUGR such as with hyperbaric oxygen therapy or specific nutritional supplementation. We review here our understanding of IUGR pathophysiology as it relates to potential therapies. PMID- 3332739 TI - Ultrasonic assessment of fetal colon by comparing ratios of colon circumference to abdominal circumference in normal pregnancy and two abnormal cases. A preliminary study. AB - Fetal gastrointestinal malformations occur with an incidence of approximately 6/1,000 births and can often be diagnosed in utero by ultrasound. Antenatal knowledge of these abnormalities can potentially decrease fetal and neonatal morbidity and mortality because the appropriate preparations can be made in advance of delivery. Changes in ultrasonic images of the fetal colon were measured by comparing ratios of colon circumference to abdominal circumference in 136 normal pregnancies. Normal values of these parameters are given for gestational age. Two abnormal case reports are included to exemplify the clinical applications. PMID- 3332740 TI - Diagnosis and treatment of twin to twin transfusion in the mid-second trimester of pregnancy. AB - Acute hydramnios in the second trimester of pregnancy associated with twin to twin transfusion is a rare and usually disastrous complication. Few infants survive the neonatal period. We report a case of acute hydramnios prior to 20 weeks of gestation secondary to twin to twin transfusion documented by fetal blood samples obtained using cordocentesis. Selective fetacide was performed using a new procedure after a pericardial effusion had failed. The hydramnios resolved and the surviving co-twin was delivered at term. PMID- 3332741 TI - Abnormal fetal cerebral blood flow velocity waveforms as a sign of an aneurysm of the vein of Galen. AB - A cerebral midline cystic lesion was detected by real-time ultrasound in utero in the absence of other congenital abnormalities. Pulsed Doppler ultrasound assessment of fetal circulation demonstrated normal peripheral and intracardiac hemodynamics associated with decreased cerebral vascular resistance. Furthermore, a markedly turbulent flow pattern was evidenced within the cerebral lesion. The presence of a cerebral arteriovenous malformation with an aneurysm of the vein of Galen was suggested and the provisional diagnosis was later confirmed by computed tomography and carotid angiography performed after birth. PMID- 3332742 TI - Sacrococcygeal teratoma. AB - The definition, natural history and prognosis of sacrococcygeal teratoma (SCT) are reviewed. Two cases of SCT are presented in detail. Both were diagnosed well before delivery and required intensive perinatal management. Both babies survived intact after removal of 30-50% of total body mass. Case selection for antenatal therapy remains a problem. Prospects for antenatal therapy are reviewed. PMID- 3332743 TI - Experience with 8 cases of prenatally diagnosed sacrococcygeal teratomas. AB - Based on an analysis of eight prenatal diagnoses of sacrococcygeal teratomas and a review of the literature on this condition, sacrococcygeal teratoma can be accurately diagnosed which is related to significant fetal wastage as well as neonatal morbidity and mortality. These tumors are usually benign and the long term morbidity, but not the overall survival rate, appears to be related to the American Academy of Pediatrics Surgical Section type of tumor. alpha-Fetoprotein can be normal or elevated and acetylcholinesterase in amniotic fluid can be present in spite of the polyhydramnios, but sonography can distinguish these lesions from neural tube defects. Nonimmune hydrops is an ominous sign, particularly in cases detected early in pregnancy. Timing and method of delivery are important considerations for neonatal survival with these lesions. However, normal survival with minimal morbidity is possible even in the largest of sacrococcygeal teratomas. PMID- 3332744 TI - Fetal sacrococcygeal teratoma. AB - Early prenatal diagnosis of fetal sacrococcygeal teratoma (SCT) has enabled the perinatal team to institute management of this condition during the perinatal period. We report 2 additional cases to our previous 27 cases including 1 which represents the earliest diagnosis of SCT. Fetal SCT behaves in a different manner than neonatal SCT. In utero manipulation of fetal SCT may be possible if diagnosis is made during the second trimester. PMID- 3332745 TI - NSAID-induced gastric mucosal damage. AB - Gastric mucosal damage is a common side effect of nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs may cause gastrointestinal symptoms, gastric erosions, peptic ulcers or upper gastrointestinal bleeding. Therefore, NSAIDs should be used cautiously in patients with a history of gastrointestinal lesions. Drugs that may be useful in preventing or treating NSAID-induced gastric mucosal injury are under intensive clinical investigation. PMID- 3332746 TI - Ovarian cancer. PMID- 3332748 TI - Skin tumor of T accessory cells (interdigitating reticulum cells) with high content of T lymphocytes. AB - A case of T-accessory cell tumor of the skin in a 67-year-old man is reported. The limbs, shoulders, and face were affected, but no visceral involvement is evident 6 years after onset. Tumor cells are nonphagocytic mononuclear cells with folded irregular nuclei. Immunologically, cells were positive for S100 protein, HLA-DR, Ki-M1, Leu 3a (CD4), Leu 6 (CD1); that is, they are identical to the phenotype of Langerhans or interdigitating reticulum cells (IDCs). Birbeck granules were absent. The clinical course appears to be less aggressive than that of the reported IDC sarcomas in other anatomical sites. The similarity of our case to some cases of so-called "non-X histiocytosis" of the skin is discussed. It is suspected that the "non-X histiocytosis of the skin" reported in the literature might have included T-accessory cell tumors, especially those of IDC origin. More immunological studies on the histiocytic disorders of the skin are necessary to clarify their cytogenesis. PMID- 3332747 TI - T-cell signet-ring cell proliferation in the skin simulating true histiocytic lymphoma. AB - We report the case of a solitary ulcerating lesion on the elbow of a 32-year-old man. Routine histopathological examination strongly suggested a histiocytic malignancy. However, electron-microscopical, enzyme-cytochemical, and immunological studies revealed that the "tumor" cells were T lymphocytes with an unusual (Leu 1+, Leu 3a+, Leu 4+, Leu 5b+, OKT4+, HLA-DR+, Ki-1+, Leu MI+) immunological phenotype and an even more uncommon morphology characterized by the development of giant multivesicular bodies giving some cells a signet-ring cell appearance, and autophagocytosis. The lesion healed spontaneously, notwithstanding its malignant histology. PMID- 3332749 TI - C5a as a mediator of cutaneous inflammation. AB - C5a is an 11,000-dalton fragment of the fifth component of complement with potent anaphylatoxic and leukocyte chemotactic activities. Because C5a may play an important role in selected skin disorders as well as in systemic diseases with cutaneous manifestations, we have studied the clinical and histologic alterations produced by the intradermal injection of this potent soluble mediator of inflammation in human skin in vivo. These studies have outlined the biologic properties of human C5a within the context of cells resident in the skin, the cutaneous microvasculature, and interacting cellular elements of peripheral blood. PMID- 3332750 TI - The language of Hippocrates. PMID- 3332751 TI - Salomon Stricker (1834-1898). Pioneer experimental pathologist. PMID- 3332752 TI - The man behind the eponym. Paul Langerhans--life and work. Part I. Childhood, early education, and college education. PMID- 3332753 TI - The man behind the eponym. Paul Langerhans--life and work. Part II. Postgraduate studies, travels, first signs of disease, Madeira. PMID- 3332754 TI - [Internal irradiation]. PMID- 3332756 TI - [Where are we with the problem of legionellosis?]. PMID- 3332757 TI - Skin signs of internal malignancy. PMID- 3332758 TI - Treatment of pityriasis versicolor: comparison of sulconazole nitrate 1% solution and clotrimazole 1 % solution. PMID- 3332759 TI - Herpes gestationis with multiple recurrences. PMID- 3332755 TI - The impact of genetic engineering on the commercial production of antibiotics by Streptomyces and related bacteria. AB - Developments in Streptomyces genetics that have laid a foundation for this field over the past ten years are reviewed and discussed to suggest how this knowledge might useful for improving the commercial production of antibiotics. This brief analysis predicts a bright future for the application of Streptomyces genetics in antibiotic production. PMID- 3332760 TI - Ribosomal modification and resistance in antibiotic-producing organisms. AB - Antibiotic producing organisms defend themselves against their products in a variety of ways including modification of the normal target sites for antibiotic action. In the ribosomal context, some organisms that produce inhibitors of protein synthesis render their own ribosomes refractory to the autogenous drugs via specific methylation of ribosomal RNA. Such hints that antibiotics might normally recognize RNA within the ribosome, complement other data in suggesting that RNA might be intimately associated with--and, in evolutionary terms, might originally have constituted--various functional sites within the ribosome. PMID- 3332761 TI - Structure and function of candidate vaccine antigens in Plasmodium falciparum. AB - Analysis of Plasmodium falciparum antigens expressed in Escherichia coli has identified several different proteins as potential vaccine components. Fragments of one of these antigens, the ring-infected erythrocyte surface antigen (RESA) have been used to protect Aotus monkeys against overwhelming infection with P. falciparum. In this vaccine, trial protection correlated with antibody responses to two of three repetitive sequences in RESA. RESA is released from merozoites and becomes associated with the erythrocyte membrane at the time of merozoite invasion. The 3' repeat structure of RESA encodes a polyacidic sequence that has homology with the N-terminal sequence (cytoplasmic domain) of band 3, the erythrocyte anion transporter. These homologous sequences both include a recognition sequence for a protein tyrosine kinase. It is postulated that RESA disrupts the normal intermolecular interactions of the cytoplasmic domain of band 3 and that phosphorylation of RESA by an erythrocyte membrane kinase in some way regulates this function of RESA. PMID- 3332763 TI - Topogenesis of glycolytic enzymes in Trypanosoma brucei. AB - The protozoan haemoflagellate Trypanosoma brucei, differs from other eukaryotic cells in that it contains nine enzymes involved in glucose and glycerol metabolism which are associated with microbody-like organelles called glycosomes. The information available to date indicates that glycosomal enzymes are synthesized as polypeptides of mature size. For three of them, glyceraldehyde phosphate dehydrogenase, aldolase and glycerol-3-phosphate dehydrogenase, it has been shown that they are made on free polysomes in the cytosol and are subsequently transferred to the glycosome without any secondary modification. The topogenic signal responsible for import into the glycosome must, therefore, be present in the mature protein. Remarkable differences exist between the latter proteins and other glycolytic enzymes: (i) most glycosomal proteins have an apparent Mr which is 1-5 kDa larger than their homologous counterparts from the cytosol, or from other organisms; (ii) they have a high net positive charge. Based on the modelling of three glycosomal sequences in the respective homologous structures, it is thought that the topogenic signal may consist of a unique insertion, containing one or more basic amino acids which, together with additional positive charges elsewhere, constitute two positive hot spots approximately 4 nm apart on the surface of the protein. Such common elements, unique for the glycolytic enzymes from the Trypanosomatidae, lend themselves as excellent targets for the development of new drugs. PMID- 3332762 TI - Schistosome elastases: biological importance, structure, function and stage specific expression. AB - Larval schistosomes (Digenea: Trematoda) invade their definitive host by directly penetrating the skin. During the process they secrete a number of macromolecules, ostensibly to facilitate their entry. Among these we have identified and characterized a dominant proteolytic species: a serine protease capable of fragmenting keratin, types IV and VIII collagen, proteoglycan, fibronectin, laminin, and elastin. The enzyme exhibits the specificity characteristic of elastases, has a molecular mass of 30,000 Da and pI of 7.8, and is potently immunogenic in its native form. Specificity of the active site has been analysed, tetrapeptides having large hydrophobic or aromatic amino acids at size P1 serving as best substrates. The amino terminal 20 amino acids of the mature enzyme have been sequenced and the information derived has been used to construct an oligonucleotide (22-mer) complement of its corresponding mRNA. The latter has been used to establish, by Northern analysis, that expression of the enzyme is stage specific (differing in this respect from most schistosome immunogens), and under transcriptional control. Transcripts are encoded by a multigene family. Several cDNAs hybridizing to the oligonucleotide have been isolated, subcloned into bacteriophage M-13, and sequenced by the di-deoxy method. It is our expectation that this line of investigation will lead towards: (i) an anti infection vaccine; (ii) a means for chemically preventing infection (using enzyme inhibitors), and/or (iii) a rapid diagnostic assay of prepatent infection. PMID- 3332764 TI - DNA probes in human disease. AB - Nucleic acid probes are able to detect the presence of particular sequences in a sample down to the level of a few hundred molecules. They can discriminate between similar sequences to a resolution of better than one part in 10(9). They are capable of detecting inherited defects in tissues where the phenotype is not being expressed, and in cases where the biochemical aberration is not understood. They can characterize acquired diseases in somatic cells (both tumours and infectious agents). Additionally, they can be used to characterize multifactorial (either polygenic or requiring an environmental stimulus to interact with a genetic predisposition) diseases. Nucleic acid 'fingerprints' provide an unequivocal identification of the origin of cells which may be applied in criminal law, civil law, and in the follow up to bone marrow transplants. In spite of this tremendous potential, there is still a large gap between their use in research laboratories and their widespread application in pathology laboratories. There are two basic reasons for this. The first is the number of labour-intensive steps involved in the various 'blotting' techniques which greatly reduces the rate at which assays may be performed. The second is the need to use probes labelled with isotopes which are short-lived and may require stringent safety measures to be employed. Recent work both in this laboratory and elsewhere is designed to circumvent both these problems. PMID- 3332765 TI - Molecular genetic approaches to cystic fibrosis. AB - Cystic fibrosis (CF) is the most common lethal genetic disease of white populations. The underlying biochemical defect remains unknown, but recently polymorphic DNA markers linked to the cystic fibrosis gene have been discovered. These markers provide useful tools both for antenatal diagnosis and carrier detection, and for isolating the cystic fibrosis gene. In this paper we present data summarizing the results of retrospective and prospective antenatal series as well as a report on molecular approaches to isolation of the cystic fibrosis gene. PMID- 3332766 TI - Apolipoprotein B gene: plasma cholesterol and atherosclerosis. PMID- 3332767 TI - The molecular biology of the morbillivirus (measles) group. AB - The morbilliviruses are a closely related group of important human and animal pathogens. The best known members of the group are measles virus in man and canine distemper virus in dogs. The group also includes two other serious animal diseases, rinderpest or cattle plague and peste des petits ruminants in sheep and goats. The latter viruses are of great economic importance in Africa, Asia and the Middle East. Persistence of these viruses in some form is a possible mechanism whereby life-long immunity is conferred on an infected individual. In addition to the severe, often fatal, acute disease these viruses can, in rare cases, lead to a fatal chronic disease of the CNS. Molecular biological studies will be described which are beginning to elucidate their evolutionary relationships and to provide a basis for understanding the role of individual virus genes in pathogenesis. PMID- 3332768 TI - The development of novel hepatitis B vaccines. AB - The development of vaccines against hepatitis B has proceeded along four main lines. (i) Human plasma-derived vaccines are safe, effective, and in general use. (ii) Subunit polypeptide vaccines formulated in micelles have reached the stage of clinical trials. (iii) Recombinant DNA vaccines have been produced in prokaryotic and eukaryotic cells, notably in yeast. The yeast-derived recombinant vaccine has proved safe and effective in extensive clinical trials, eliciting antibodies of equal quantity and quality of specificity to those elicited by plasma-derived vaccine. DNA recombination has also been applied to the development of hybrid vaccinia virus vaccines which are capable of immunological 'priming'. (iv) Finally, chemical synthesis has succeeded in producing small peptides which include specific epitopes eliciting antibody responses in experimental animals. PMID- 3332769 TI - From Jenner to genes--the next generation of virus vaccines. AB - Vaccination has played a major role in the control of many virus diseases affecting man and animals. Two kinds of vaccines are in use: (i) attenuated vaccines, which infect the host without causing disease and (ii) killed vaccines, which consist of large amounts of virus particles that have been inactivated by either physical or chemical agents under conditions that ensure retention of their antigenic properties. Despite the success of vaccination there is still a need for products that are safer and more effective. Even more important, there are diseases for which 'conventional' vaccines are not available. New approaches that will ultimately solve these problems have been provided by the detailed analysis of viruses at the molecular level. Thus we are now beginning to understand virulence in molecular terms and particularly rapid advances have been made with poliovirus, holding out the promise of a completely avirulent attenuated vaccine. With killed vaccines, the major advance has come from the recognition that the immune response to most viruses is determined by a single protein. By identifying the genes coding for these proteins it has become possible to express them in large quantities not only in a variety of cells, but also in virus vectors that can be grown in vitro and in vivo. Moreover, in some instances, fragments of immunogenic proteins, small enough to be synthesized chemically, have been shown to be protective. The rapid pace of these conceptual and technological advances leads the author to the expectation that viruses and antigens that are defined in precise chemical terms will form the basis of the vaccines of the future. PMID- 3332770 TI - Cloned antigen genes of Brugia filarial parasites. AB - Human lymphatic filariasis is a chronic, potentially debilitating disease caused by Brugia and Wuchereria species of parasitic nematodes. The spectrum of clinical manifestations appears to be related to the immune response of individuals to invasive larvae, adult worms and circulating first-stage larvae (microfilariae). Potential immunopathological outcomes place constraints on vaccine development, emphasizing the need to understand the basis of immunity and pathology. Clones coding for a number of distinct antigenic proteins of Brugia pahangi and Brugia malayi have been isolated via immunological screening of a cDNA expression library. A small number of these expressed peptides show exclusive reactivity with antibody from amicrofilaraemic, potentially immune individuals. Surprisingly, a dominant immunogen isolated with human antibody is the filarial parasite homologue of heat shock protein (hsp) 70. This protein is constitutively expressed in both insect- and mammalian-dwelling parasitic stages, but does not appear to presented to the host immune system in intact worms. PMID- 3332771 TI - Histological and biochemical observations of developing enameloid of the Sea Bream. PMID- 3332772 TI - New artefacts for old: an alterative method of preparing hard and soft tissue interfaces of developing enamel. PMID- 3332773 TI - Resonance Raman studies of hydroporphyrins and chlorophylls. PMID- 3332774 TI - How carotenoids function in photosynthetic bacteria. AB - Carotenoids are essential for the survival of photosynthetic organisms. They function as light-harvesting molecules and provide photoprotection. In this review, the molecular features which determine the efficiencies of the various photophysical and photochemical processes of carotenoids are discussed. The behavior of carotenoids in photosynthetic bacterial reaction centers and light harvesting complexes is correlated with data from experiments carried out on carotenoids and model systems in vitro. The status of the carotenoid structural determinations in vivo is reviewed. PMID- 3332776 TI - [Long-term administration of captopril in the treatment of severe congestive heart failure]. PMID- 3332775 TI - [Interaction of lipids and lipoproteins with connective components in the vascular wall]. PMID- 3332777 TI - [The effect of ethmozin on electrical stability of the heart ventricles in dogs in the early stages of ischemia]. PMID- 3332778 TI - Modeling of a neural pattern generator with coupled nonlinear oscillators. PMID- 3332779 TI - Epidemiology and control of sexually transmitted diseases: strategic evolution. AB - During the past 10 years, the field of sexually transmitted diseases has evolved from one emphasizing the traditional venereal diseases of gonorrhea and syphilis, to one concerned with the syndromes associated with Chlamydia trachomatis, herpes simplex virus, and human papillomavirus, and then to one preoccupied with the fatal systemic infections caused by human immunodeficiency virus. PMID- 3332780 TI - Acquired immunodeficiency syndrome. AB - Acquired immunodeficiency syndrome (AIDS) is the lethal end stage of a sexually transmitted disease caused by a virus that is producing the major epidemic of our century. In this article we describe the history and epidemiology of AIDS and the disease states associated with infection with the human immunodeficiency virus (HIV), the apparent cause of AIDS. We review what is known about disease pathogenesis and present an overview of clinical management issues. In the absence of vaccine or therapy to prevent and eradicate this viral infection, we present formative educational approaches for its control. PMID- 3332781 TI - Sexually transmitted diseases. Urethritis in men. AB - Gonococcal and nongonococcal urethritis (NGU) are among the most common syndromes afflicting men. NGU is caused primarily by Chlamydia trachomatis and Ureaplasma urealyticum, but the cause is unknown in approximately 20 to 30 percent of cases. Evaluation of a gram-stained urethral smear is generally sufficient to distinguish between gonococcal and nongonococcal urethritis. Owing to the frequent coexistence of Neisseria gonorrhoeae and C. trachomatis in heterosexual men, treatment regimens for gonococcal urethritis should generally include an effective antichlamydial regimen. Complications of urethritis are uncommon, but the causative pathogens produce serious morbidity in women. Prevention of urethritis is based on identification of asymptomatically infected persons who serve as the major reservoir of infection with both N. gonorrhoeae and C. trachomatis. PMID- 3332782 TI - Sexually transmitted diseases. Lower genital tract infections in women. AB - Infections of the female urinary tract, cervix, vulva, and vagina produce a variety of overlapping symptoms, including vulvar pruritus, dysuria, dyspareunia, and increased or altered vaginal discharge. Recent studies have considerably improved our understanding of the etiology, pathophysiology, diagnosis, and treatment of these infections. PMID- 3332783 TI - Sexually transmitted diseases. Pelvic inflammatory disease and infertility in women. AB - PID is a major medical, economic, and public health problem in the United States. It is the most common serious complication of sexually transmitted diseases among young women. Of great concern is the increasing incidence of adverse reproductive consequences that are thought to be directly related to PID. The most common and important sequelae are tubal factor infertility and ectopic pregnancy. Retrospective serologic evidence has been generated by many studies implicating previous chlamydial infection as a major cause of tubal factor infertility and probably of ectopic pregnancy. Treatment of PID must include regimens effective against a broad range of pathogens, including N. gonorrhoeae and C. trachomatis. PMID- 3332784 TI - Sexually transmitted diseases. Genital ulceration with regional adenopathy. AB - The specific agent causing genital ulceration is difficult to identify without laboratory confirmatory testing including darkfield microscopy, syphilis and lymphogranuloma venereum serology, and culture for Haemophilus ducreyi and herpes simplex virus. Empiric antimicrobial therapy risks masking clinical or serologic diagnosis of syphilis. PMID- 3332785 TI - Sexually transmitted enteric and rectal infections in homosexual men. AB - Intestinal infections represent a major health problem in homosexual men. The spectrum of potential pathogens includes classic sexually transmitted pathogens, enteric bacterial and protozoan pathogens, and a wide range of opportunistic infections seen in patients with human immunodeficiency virus (HIV) infections. Diagnosis and treatment of these infections must be comprehensive, including a full microbiologic evaluation, assessment of the immuno-competence of the patient, and repeat examination following completion of therapy. PMID- 3332786 TI - Gonococcal infections. AB - Although gonorrhea rates for the 1980s appear to have plateaued or even declined slightly in developed nations, in the developing world rates appear to be continuing to increase. In recent years, worldwide gonorrhea control efforts have been compromised by the continuing emergence of antimicrobial resistance resulting from plasmid-mediated beta-lactamase production, plasmid-mediated tetracycline resistance, and chromosomally mediated resistance to many antimicrobial agents. Intensive investigation of gonococcal physiology and structure has provided insights into gonococcal pathogenesis and epidemiology. Application of knowledge gained through basic research is being used to provide improved methods of gonorrhea diagnosis and to identify components of potential gonococcal vaccines. PMID- 3332787 TI - Sexually transmitted diseases in pregnancy. AB - Sexually transmitted diseases may have a significant impact on the pregnant woman and her fetus and neonate. Infection at various stages of pregnancy may result in severe maternal disease, congenital defects, premature delivery, or neonatal infection. The clinician caring for pregnant women must be aware of the multitude of sexually transmitted diseases and their potential risks during pregnancy. PMID- 3332788 TI - Sexually transmitted diseases in children and adolescents. AB - Sexually transmitted diseases have an impact on children's health at three times in their development: during pregnancy or delivery (through maternal-neonatal transmission), during prepubertal childhood (through sexual transmission), and during adolescence (through sexual transmission). These phases must be considered distinctly by the physician, since not only the type of infection but also the management and long-term implications of the disease vary with the time period in which it was acquired. PMID- 3332789 TI - Chlamydial infections. AB - Sexually transmitted infections caused by Chlamydia trachomatis are of epidemic proportions. Since chlamydial infections are often asymptomatic, identification of infected persons is the major public health challenge in the control of chlamydial disease. Unfortunately, asymptomatic infections in women can be complicated by salpingitis, ectopic pregnancy, and involuntary infertility. The best current diagnostic test is cell culture. Direct antigen tests are cheaper and more widely available than cell culture but are less sensitive. Improved diagnostic tests, screening of groups at risk, educating patients and health care providers, and reporting of chlamydial infections will be essential in controlling chlamydial disease. PMID- 3332790 TI - Syphilis. AB - Inoculation of Treponema pallidum during intimate physical contact is followed by development of a papule that rapidly erodes, yielding the syphilitic chancre. Hematogenous dissemination results in secondary syphilis, a multisystem disease characterized by skin rash, lymph node enlargement, hepatitis, arthritis, and central nervous system involvement. In the absence of treatment, a latent period is reached after which tertiary syphilis may appear in an increasing proportion of patients, depending upon the duration of the follow-up. PMID- 3332792 TI - Developments in rapid viral diagnosis. AB - Rapid viral diagnosis is becoming an integral part of modern medical practice. Although advances in our understanding of viral diseases and in technical developments have encouraged this change in status, progress in antiviral chemotherapy is the major impetus to advances and acceptance of rapid viral diagnosis. Lab tests cannot substitute for the clinical acumen of the physician or the proper collection and delivery of the patient specimen. For most viral diseases, advances have been made in improved rapid virus isolation techniques, better and more widely available immunofluorescence, and immunoenzyme microscopic techniques, with much of the improvement provided by monoclonal antibodies. Enzyme immunoassays for antigen detection are becoming increasingly available, many commercially, and several have been accepted as standard diagnostic methods. Newer techniques, such as latex agglutination-improved enzyme immunoassays and the use of nucleic acid hybridization are under active investigation. PMID- 3332793 TI - Treatment of human immunodeficiency virus infections. AB - Effective antiviral drugs are urgently needed to treat individuals who are infected with the human immunodeficiency virus (HIV). Several compounds, such as nucleoside analogs (AZT, ddCyd), phosphonoformate, and HPA-23 inhibit reverse transcriptase. The mode of action of ribavirin and interferon alpha A is less clear. A number of compounds have been tested in early clinical trials, and AZT so far looks the most promising. New drugs should undergo rapid but thorough in vitro and animal testing. Promising compounds should be made available as soon as possible for phase I trials. PMID- 3332791 TI - Genital herpes simplex virus infections. AB - Genital HSV infection is an important sexually transmitted disease that is becoming more common. The primary infection typically is associated with systemic signs and symptoms and painful genital lesions, with a high rate of complications. Recurrences are much milder, with less frequent complications. Although many rapid diagnostic tests for genital herpes are now available, none is as sensitive or reliable as tissue culture. Dilemmas still exist regarding the best management strategy for the expectant mother at risk for transmitting HSV to the neonate, in part because of limitations in current diagnostic techniques. Although current treatment regimens with acyclovir can effectively control most symptoms and improve healing of lesions, they appear to have no effect on decreasing the frequency of subsequent recurrences. Short-term chronic suppression with acyclovir is effective in preventing symptomatic recurrences and appears to be relatively free of toxicity, but long-term studies are only now in progress. Asymptomatic viral shedding associated with either primary or recurrent infections and its contribution to sexual transmission of the disease are just now being fully appreciated, and the effect of therapy on subsequent transmission of disease remains to be determined. HSV genital infection in the immunocompromised host can produce a more severe and prolonged illness than in the normal host, but reactivation of the infection can be prevented with acyclovir suppression. Further research is needed on many aspects of the host-HSV interaction, especially regarding the factors involved in recurrences and the importance of the host's immune response to the manifestations of disease. PMID- 3332794 TI - Diagnosis and treatment of genital herpes infections. AB - Oral acyclovir is the treatment of choice for most patients with first episode genital herpes (Table 2). Therapy of first episode herpes may not be indicated in patients whose symptoms and lesions are clearly resolving at the time of presentation, and intravenous acyclovir therapy should be considered in patients with first episode herpes who require hospitalization. A viral culture should be obtained prior to initiating treatment in persons with first episode genital herpes, and typing should be performed to predict the risk and frequency of subsequent recurrences. Serologic differentiation of primary and nonprimary first episode disease is generally not performed outside the research setting. Suppression of recurrent genital herpes infections with daily oral acyclovir therapy has been shown to be safe and effective when continued for periods for up to 2 years. Oral acyclovir suppression should be considered in patients with frequent recurrences who complain of significant morbidity in association with their genital herpes infections (Table 2). The clinical benefit from episodic treatment of recurrent genital herpes infections is less dramatic. Patient initiated therapy with oral acyclovir at the first sign of prodome or lesions should be considered in patients with relatively severe recurrences who are not candidates for suppressive treatment. Virologic confirmation of infection is encouraged. Oral acyclovir is the treatment of choice for short-term or long-term suppression in immunocompromised hosts, although short-term suppression with intravenous acyclovir may be indicated for persons who cannot take oral medications. Episodic treatment with topical, oral, and intravenous acyclovir is effective in immunocompromised patients, but topical treatment should be limited to persons with external lesions only. PMID- 3332795 TI - The management of varicella and zoster infections. AB - The varicella-zoster virus causes chickenpox and shingles. Antiviral drugs like acyclovir ameliorate certain severe forms of these infections, particularly as they present in immunodeficient patients. Varicella-zoster immune globulin prevents chickenpox, but a more desirable and effective strategy entails administration of a live-attenuated vaccine. PMID- 3332796 TI - Ribavirin aerosol treatment of serious respiratory syncytial virus infection in infants. AB - Bronchiolitis is one of the most serious pulmonary infections commonly caused by respiratory syncytial virus (RSV). RSV disease occurs in yearly epidemics and is most severe in children 1 year of age or younger. Approximately 1 in 50 to 1 in 100 infants are hospitalized after their first infection, and mortality fluctuates between 0.5 and 5.0 per cent. Patients with underlying conditions such as congenital heart disease and bronchopulmonary dysplasia are at higher risk for morbidity and mortality. Methods for rapid diagnosis of RSV infection and the advent of specific therapy with aerosolized ribavirin have revolutionized the management of hospitalized patients with moderate to severe disease. A 3- to 5 day course of ribavirin plus supportive measures should be used in infants who prove to be infected by RSV and who are deteriorating on traditional supportive therapy, and/or who have underlying cardiac and/or pulmonary or immune defects. PMID- 3332797 TI - Ribavirin aerosol treatment of influenza. AB - In this article we have described the clinical and laboratory features of uncomplicated influenza in college students and its treatment with ribavirin aerosol. The disease presents as an acute febrile systemic illness of short duration that varies little from patient to patient. Peripheral blood cell changes in the infection are also quite specific and very consistent. Polymorphonuclear cell counts are slightly increased above normal early in infection at a time when lymphocyte counts were greatly reduced. As lymphocyte numbers increase at the third day of illness, polymorphonuclear cell counts diminish substantially. Eosinophil counts fluctuate in a pattern similar to that of lymphocytes. Basophil, monocyte, and band cell counts are increased at admission and thereafter decline in numbers. Reticulocytes and platelets are reduced during acute illness. We assume that changes in peripheral white blood cell counts during influenza result from migration of cells to the inflamed respiratory tract and subsequent resupply of the various types of cells to the circulation from other sites in the body. The cellular alterations in the circulation and at the site of infection are of fundamental importance in the pathogenesis of infection, and a better knowledge of them should open new avenues for prevention and treatment. Aerosol treatment was shown to alleviate the symptoms of influenza and to reduce the shedding of influenza virus from the respiratory tract. No evidence of untoward effect of ribavirin treatment on peripheral white or red blood cells was found, and a wide range of clinical chemical tests revealed no toxic effects of treatment. There was no pulmonary irritation detected from the treatment. Reference was made to prompt recovery of four patients with influenzal pneumonia treated with ribavirin aerosol. Ribavirin aerosol must produce its major therapeutic effect through inhibition of virus replication at the sites of infection in the respiratory epithelium. This appears to result mainly from interference with viral messenger RNA initiation and elongation. This is best demonstrated by the prompt decline in viral shedding in treated patients. The associated prompt clinical improvement suggests that illness results from continued virus replication, and when virus replication is retarded, improvement follows. Although treatment promptly reduces illness and virus shedding, antibody response is not reduced in treated patients. We emphasized that ribavirin aerosol had a major therapeutic effect on infections caused by both influenza A and B viruses, and the picture of illness with these types of influenza was not clinically distinguishable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3332798 TI - Rimantadine hydrochloride and amantadine hydrochloride use in influenza A virus infections. AB - Amantadine and rimantadine are oral antiviral drugs useful in the prophylaxis and treatment of influenza A virus infections. This article reviews the pharmacology, antiviral activity and mechanism of action, pharmacokinetics, toxicities, efficacy, and clinical applications of these agents. When administered in equivalent dosages (200 mg per day), rimantadine has prophylactic efficacy comparable to amantadine but lower potential for causing adverse effects. Despite structural similarities, these drugs differ significantly in their pharmacokinetics, and these differences may account for rimantadine's more favorable toxicity profile. Both drugs provide therapeutic benefit if administered early in uncomplicated influenza, and studies are currently in progress to determine the effectiveness of oral rimantadine in preventing or treating the serious complications of influenza A virus infections. PMID- 3332799 TI - Recent developments in antiviral chemotherapy. AB - As can be seen from the preceding brief discussion, the prospects for new antiviral agents for the treatment of viral diseases ranging in severity from the common cold to AIDS appear promising. The latest advances in technologies such as crystallography, genetic engineering, and monoclonal antibodies are all being applied to the discovery of new ways to inhibit virus-specific processes. In addition, the development of diagnostic tests for viral diseases has proceeded at a rapid pace that should facilitate the proper use of the antivirals when they become available. The one lesson that has been learned in the antiviral field over the past decade is that virus-specific inhibitors do exist, and if an essential virus-specific process or protein can be identified, it is likely that a molecule can be found to inhibit or inactivate it. PMID- 3332800 TI - Lipid peroxides in gingival fluid and gingival tissue of patients with marginal periodontitis. PMID- 3332802 TI - Surgical procedures in adult rheumatoid arthritis. PMID- 3332801 TI - Population genetics of pathogenic bacteria. PMID- 3332803 TI - The phenomenology of tics. PMID- 3332804 TI - Charcot on Parkinson's disease. AB - Charcot saluted Parkinson for his early observations, but condemned his use of the term "paralysis agitans." He emphasized that patients were neither dramatically weak nor were they necessarily plagued with tremor. Charcot suggested the name "Parkinson's disease," although he could not resist the comment in his amphitheater lecture series at the Salpetriere that French physicians (unnamed) had probably described the disorder before 1817. Tremor, rigidity, postural instability, and bradykinesia were all recognized by Charcot. He classified the disorder as a "nevrose," meaning a neurologic disorder without a known pathologic lesion, and found little benefit from therapies available at the time, including belladonna and ergot products. PMID- 3332806 TI - Acetazolamide responsive hereditary paroxysmal ataxia. AB - The fourteenth family with an apparently autosomal dominant paroxysmal ataxia is described. As in the seven families described since 1978, acetazolamide completely cured the attacks. A possible mechanism of action of acetazolamide is discussed. PMID- 3332805 TI - Clonidine in the treatment of essential tremor. AB - The effect of clonidine treatment (average dose 0.4 mg/day) was investigated in 10 patients with essential tremor in a double-blind placebo-controlled design. Tremor amplitude and frequency were recorded with an accelerometer. Tremor was not significantly altered by clonidine therapy. Side effects were common. It is concluded that clonidine is not effective treatment for essential tremor. PMID- 3332807 TI - Adrenergic beta 2-selective blocker in isoprenaline-enhanced essential tremor. AB - A beta 2-selective adrenergic-receptor-blocking drug, ICI 118.551, 150 mg/day, prevented almost as effectively as the nonselective antagonist propranolol, 240 mg/day, the isoprenaline enhancement of essential tremor amplitude. PMID- 3332808 TI - [The importance of zinc in child nutrition]. PMID- 3332809 TI - [Recent attainments in the immune prevention of rubella]. PMID- 3332810 TI - [Prospects for a vaccine against the infectious hepatitis virus]. PMID- 3332811 TI - [Development of measures for preventing dental caries. The use of fluoride: an update]. PMID- 3332812 TI - [The diet and caries]. PMID- 3332813 TI - [Lyophilized foods: hygienic and technological aspects]. PMID- 3332814 TI - [Epidemiology of biliary lithiasis]. PMID- 3332815 TI - [New aspects of the prevention of atherosclerosis]. PMID- 3332816 TI - Pediatric diencephalic gliomas--a review of 18 cases. AB - Eighteen cases of biopsy-proven pediatric diencephalic gliomas are reviewed in terms of clinical presentation, radiographic features and pathological findings. Treatment included radiation therapy (RT) in 14, chemotherapy in 4 and conservative management in 3. Actuarial survival and quality of life are analyzed. We conclude that: (1) thalamic involvement portends a poor prognosis both in terms of histology and survival, (2) beneficial effects of RT are difficult to demonstrate and (3) therapy for pediatric diencephalic gliomas should be individualized and long-term spontaneous remissions may occur. PMID- 3332817 TI - Recurrent brain tumors in children. AB - A significant cohort of children with central nervous system tumors will fail initial therapeutic intervention and demonstrate recurrent disease. Treatment of children with these recurrent tumors requires a comprehensive multidisciplinary approach, with consideration of both histologic classification and anatomic location of the tumor. The choice of the specific therapeutic modality selected should reflect institutional experience and seek to advance the treatment of brain tumors in children. Children at Duke Medical Center with biologically indolent tumors and clinical or significant radiographic evidence of recurrence (low-grade/benign tumors with greater than 2-year recurrence-free interval) are usually treated by repeat surgical intervention. Children whose initial therapy did not include radiotherapy are considered for irradiation, while those previously irradiated are observed or occasionally considered for chemotherapy. Children with biologically aggressive tumors (high-grade lesions or early recurrence) are offered neurosurgical intervention if there is considerable mass effect, and subsequently enrolled on phase II chemotherapy protocols, reflecting an institutional commitment to exploring the role of this modality in the treatment of pediatric brain tumors. Children with recurrent brain tumors may derive benefit from this aggressive comprehensive approach, achieving a prolonged and quality survival. PMID- 3332818 TI - [Vaccines with anti-idiotypic antibodies]. PMID- 3332819 TI - [Therapeutics of aplastic anemia]. PMID- 3332820 TI - [Calcium hydroxide as a dental material]. PMID- 3332821 TI - [Functional crossbite in premolar/molar region: Quad-helix or removable appliance?]. PMID- 3332822 TI - Embryos, ethics and women's rights. Exploring the new reproductive technologies. PMID- 3332823 TI - Women's health and the new reproductive technologies. PMID- 3332824 TI - A womb of his own. AB - Although some feminists formerly saw utopian possibilities in reproductive technology, many now fear that the new technologies are turning women's bodies into test tubes. They feel that these technologies are designed less to help infertile women than to appease men's envy of women's reproductive power. The consequences of the new technologies for the psychology of women and children and the future creation of culture are open questions. Should the technologies succeed in taking reproduction out of the body altogether, it remains to be seen whether women will gain in freedom, or whether this will simply fulfill the age old misogynistic fantasy of depriving women of their central place in procreation. PMID- 3332825 TI - Psychological effects of the new reproductive technologies. AB - Four psychological principles help us to understand the psychological effects of the new technologies: (1) Special circumstances of parenting and birth will stimulate fantasies in parents and children, which in turn influence the child's personality and identity; (2) Human parenting does not require a biological connection; nonbiological parents can be equally effective nurturers; (3) Good parenting involves a psychological interaction beginning at birth, so that early and permanent opportunity for attachment is important for normal development; (4) New technologies relieve the psychological pain of infertility and provide benefit by giving some individuals the opportunity to be parents. The psychology of surrogate mothers is also discussed. PMID- 3332826 TI - In vitro fertilization: ethical issues. AB - This paper presents an overview of ethical issues concerning IVF. The first section evaluates specific ethical issues; the medical understanding of IVF, the development of the procedure, the risks of the procedure, and issues related to consent. The second part of the paper reviews broader issues: the allocation of resources, who receives the benefits, implications of IVF, and feminist issues. This review of ethical issues presents a framework to understand and evaluate the value dimensions raised by this technology. PMID- 3332827 TI - Moral reflections on the new technologies: a Catholic analysis. AB - New technologies of conception bring into being beautiful babies. The wonder of these children, and of the technologies themselves, can tempt us to abbreviate ethical reflection on the moral appropriateness of initiating human life in this way. However, the moralists of the Catholic Church, along with many others, judge that human life should originate in acts of love between parents, not in productive acts of technologists. Scientific help for people desiring to generate a child out of their own being should be distinguished from scientific substitution for human acts of love in originating life. The child must be recognized as an equal, not as a product, subject to quality control. To radically alter our ways of generating human life without sufficient moral reflection is to generate human pain and moral dilemmas that we have not begun to fathom. PMID- 3332828 TI - Procreative liberty, embryos, and collaborative reproduction: a legal perspective. AB - This article discusses the implications of a constitutionally protected right to procreate using a wide range of reproductive choices made possible by noncoital reproductive technologies, including embryo freezing and donation and surrogate gestation. After establishing the constitutional basis for a positive right to procreate, it discusses the extent to which concerns about the welfare of embryos, offspring, donors, and surrogates justifies limitation on reproductive choice involving these technologies. While tangible harm to offspring and protection of the free choice of reproductive collaborators may justify regulation, moral condemnation of noncoital techniques and concerns about the reifying effects of their use are an insufficient basis for state restriction. PMID- 3332829 TI - Reproductive technologies and the bottom line. AB - Reproductive technologies have turned out to be creatures of the marketplace, a fact we did not foresee. Because of this commercialization, women must be as careful in selecting a clinic as in buying a used car. Where initially it appeared that government would impose test-tube babies and genetic engineering on society, the great irony is that we now look to government to protect us from the Brave New World. PMID- 3332830 TI - Technology, power and the state. AB - Technical innovations may produce not only the changes they were intended to effect but also lead to consequences which are unexpected and sometimes destructive. There is an intimate relation between technological innovation and political power. Any great advances in reproductive technology are very likely to be controlled and commandeered by the state with all kinds of unforeseeable consequences. PMID- 3332831 TI - Eugenics: new tools, old ideas. AB - Prejudices against people who have noticeable disabilities have resulted in needless social and economic barriers to their participation in society. In Germany under the Nazis, a movement for eugenics, or "racial hygiene," led to the sterilization and, later, the elimination of people with particular mental or physical disabilities. In the United States, earlier in the century, the eugenics movement produced compulsory sterilization laws. At present, physicians and scientists are developing techniques for prenatal diagnosis of increasing numbers of inherited diseases and disabilities, although more babies and children are needlessly disabled because of poverty and accidents than for genetic reasons. Such prenatal tests are being hailed as progress, yet their availability is once again turning pregnancy into a medical event and confronts women with decisions and choices that can be extremely difficult. PMID- 3332832 TI - Women and reproductive technologies: a partially annotated bibliography. AB - This bibliography is a resource for further information about Women and Reproductive Technologies. The references are categorized as General Information, Law and Policy Considerations, and Information about Specific Technologies. It also lists periodicals, organizations, and other bibliographies relating to this subject and is current through March 1986. PMID- 3332833 TI - In vitro fertilization, GIFT and related technologies--hope in a test tube. AB - In vitro fertilization (IVF) is demanding, expensive and inefficient. Nevertheless, tens of thousands of couples have undertaken the procedure because of their intense desire to have a biological child. Modifications of the current IVF process--simplification of ovulation induction and prediction of successful cycles; use of ultrasound instead of laparoscopy for egg retrieval; freezing of excess embryos for later replacement; and the substitution of GIFT (gamete intra fallopian transfer) for IVF when it is indicated--may increase its acceptability to couples and improve success rates. Meanwhile, IVF has had tremendous impact on our understanding of fertility and should help physicians in their approach to infertility in the future. It has also ushered in a new era of genetic engineering whose potential we have not yet begun to realize. PMID- 3332834 TI - Fetal imaging and fetal monitoring: finding the ethical issues. AB - Ethical issues are raised in connection with three technologies used to detect abnormalities or distress in the fetus in late pregnancy and during labor: (1) Ultrasound for fetal diagnosis, a technology used with increasing frequency in pregnancy and labor and one which some are advocating for routine use in pregnancy; (2) The newest of the imaging technologies, magnetic resonance imaging (MRI), which is not now commonly used for fetal imaging, but may soon be; (3) The electronic fetal monitors, some of which work by application of the physical principles of ultrasound behavior and raise many of the same ethical issues. This paper argues that women-centered critiques of birthing technologies augment the concern with the health risks posed by those technologies with concerns about the risks that they pose to human relationships. PMID- 3332835 TI - Power, certainty, and the fear of death. AB - Reproductive technology has been poorly used because both health care providers and clients unrealistically expect it to prevent all death and uncertainty. Because of this we often get the risks, side effects, and inaccurate information without benefits. Poorly used reproductive technology also deskills both providers and clients. Used realistically and controlled by women--birthing women and midwives--this technology can be of great benefit to us and our children. PMID- 3332836 TI - Reproductive technologies: the two sides of the glass jar. AB - From our knowledge of fertilization and implantation, new methods of reproduction have been developed. These new reproductive technologies make possible new parenting arrangements, resetting the biological clock for women, selecting the timing of birth, sex and number of children, pre-implantation diagnosis and gene replacement. The new ways of making babies present us with a myriad of ethical, legal, social and psychological concerns. PMID- 3332837 TI - Reproductive technology and the commodification of life. AB - This paper suggests that the key unifying concept in the development and application of new reproduction technology has been the increasing commodification of life--treating people and parts of people as marketable commodities. This commodification process is made most dramatically clear in (1) prenatal diagnosis, in which the fetus is treated as a product subject to quality control measures and women are treated as producers without emotional tie to their products and (2) in so-called "surrogacy" arrangements in which an actual price tag is placed on pregnancy, and women sell both their "labor" and their "product." PMID- 3332838 TI - I remember--1942 and the 118th General Hospital. PMID- 3332840 TI - ABC of modern vaccines. PMID- 3332839 TI - Prevention of pressure sores. A comparison of new and old pressure sore treatments. PMID- 3332841 TI - Food fats, good and bad. PMID- 3332843 TI - The evolution of vascular surgery and the Nobel Prize. PMID- 3332842 TI - Augmentin (intravenous then oral) compared with cefuroxime followed by cephalexin for chest infections in hospitalised patients. PMID- 3332844 TI - Aortic stump closure: a new technique. AB - The usual closure of the aortic stump results in a cul-de-sac which favors secondary rupture. A new procedure utilizing an anterior-posterior suture line in two layers is described which creates a median strut. It allows a secure suture line in a short aortic stump, and may enhance the splitting of blood flow between the renal arteries. PMID- 3332846 TI - Arterial substitutes: thirty years of success and failure. PMID- 3332845 TI - The influence of duplex scanning on early patency rates of in situ bypass to the tibial vessels. AB - Duplex scanning was used in the follow up of 49 in situ infrapopliteal bypasses per formed for limb salvage using the valve incision method. In 19 cases (39%) the peroneal artery was the best available vessel for distal insertion; the anterior tibial and dorsalis pedis were used in 17 cases (35%) and the posterior tibial artery and tibioperoneal trunk in 13 cases (26%). In the early postoperative period three AV fistulas presented with painful skin lesions. These were located using duplex scanning and following ligation rapid resolution followed. Primary patency at one month was 87% and was increased to 96% by successful correction of four out of six failed bypasses. A total of 11 stenoses were found in five bypasses between three and 15 months postoperatively. In four of these patients the ankle/arm index decreased by at least 0.15 between examinations. A comparison was made between the spectral analysis on duplex scanning and the findings on arteriography and at operation. Peak systolic frequencies greater than 6,000 Hz were associated with 50% or greater reduction in vein bypass diameter. The majority were corrected using vein patch angioplasty. Primary cumulative patency at two years was maintained at 68% while correction of two out of seven bypass failures raised this to 80%. Duplex scanning allows precise definition of vein bypass pathology, facilitates operative correction and increases long-term limb salvage. PMID- 3332847 TI - Duplex scanning for noninvasive assessment of both carotid luminal diameter and atheromatous plaque morphology. AB - The value of Duplex scanning in 50 consecutive patients with symptomatic carotid stenosis was evaluated. Compared with contrast arteriography, the sensitivity of Duplex scanning, for a greater than 50% internal carotid diameter reduction, was 90% (66/73) with a specificity of 96% (26/27). The overall agreement between Duplex and contrast arteriography as measured by the Kappa value was K = 0.561. One of the 13 arteries felt to be occluded on Duplex scanning was radiologically found to be patent. Excluding the six normal and 13 occluded arteries, 81 carotid plaques were defined as either heterogeneous, suggestive of intraplaque hemorrhage or as homogeneous. Twenty-four of the 32 asymptomatic cerebral hemispheres were associated with ipsilateral homogeneous plaques, while 30 of the 49 symptomatic hemispheres had heterogeneous plaques in the ipsilateral carotid, (p less than 0.001). This study confirms the accuracy of duplex scanning in detecting internal carotid stenosis as well as in identifying plaques which are morphologically heterogeneous and more likely to be associated with ipsilateral cerebral hemispheric symptoms. PMID- 3332848 TI - Reproducibility of transcutaneous continuous-wave Doppler testing of the carotid arteries. AB - Hand-held, continuous-wave Doppler probes, coupled with sound spectral analysis, can successfully predict carotid artery stenosis. Changing either the emitting frequency of the probe, the beam/artery angle of the carotid flow velocity (e.g. cardiac output) may alter the recorded frequency shifts. These effects raise questions as to the efficacy of this technique to serially follow carotid atheroma for progressive stenosis. To test the inherent problems with this methodology, a study of reproducibility was conducted. Two Doppler probes (5 MHz and 8 MHz) were compared at the same sitting in 24 patients; 12 were restudied on two subsequent occasions. Peak systolic frequency was 135% higher with the 8 MHz probe; this was lower than the 160% calculated by substitution for emitting frequency in the Doppler formula. The linear correlation coefficient of the two probes was 0.88. In relationship to established laboratory criteria of a greater than 75% area stenosis, no errors were noted with the 5 MHz probe while four errors were noted with the 8 MHz probe. A serial study variation of peak systolic frequency was noted for both probes; these variations did not cross established criteria levels of a severe stenosis when the 5 MHz probe was used, but did with the 8 MHz probe for two carotids. A standard examining probe is recommended. Angle and cardiac output changes do result in peak systolic frequency variation from test to test, but these were not clinically significant with the 5 MHz probe. Thus, significant changes during follow-up testing should provide an index of evolving carotid stenosis. PMID- 3332849 TI - Noninvasive assessment of cerebrovascular disease. PMID- 3332850 TI - Basic data related to clinical decision-making in abdominal aortic aneurysms. PMID- 3332851 TI - Role of the ABL oncogene tyrosine kinase activity in human leukaemia. AB - A great deal of information has emerged over the past decade regarding the gene structures and corresponding protein products of the cellular and transformation associated forms of the ABL tyrosine kinase family. Many reports have also detailed the biological effects of these proteins (particularly the viral ABL forms) on a broad range of cell types. However, in spite of all these research efforts, the precise role of the ABL gene in normal and neoplastic growth remains to be determined. To elucidate the mechanism of action of normal and altered ABL proteins, it is imperative to identify their relevant cellular substrates and establish the role of the ABL target proteins in transformation and normal cellular growth. The availability of temperature-sensitive ABL proteins, coupled with the use of sensitive anti-phosphotyrosine antibodies, should be useful in this respect. Purification of enzymatically active, intact forms of the ABL proteins produced in insect cells by employing baculovirus expression vectors should permit direct comparison of the biochemical properties and tertiary structures of the various members of the ABL protein kinase family. Such studies will aid in understanding the nature of the alteration of ABL which results in the activation of its transforming potential. Furthermore, the availability of purified ABL proteins should permit examination of interactions of ABL with other growth-regulatory proteins, such as growth factor receptors. It has been shown that transformation-associated ABL proteins interact with the IL-3, IL-2 and GM CSF growth-factor pathways. These and other components of the cellular signalling pathways are potential ABL targets. The elucidation of ABL function by a variety of approaches such as those described above will ultimately aid in the development of far-reaching therapeutic treatments for at least two forms of human leukaemia: Ph positive CML and Ph positive ALL. PMID- 3332852 TI - Ph positive CML cell lines. PMID- 3332853 TI - Bone marrow transplantation for CML. PMID- 3332854 TI - Chronic myelogenous leukaemia: a model for human cancers. AB - In this chapter I reviewed the biological and molecular abnormalities associated with CML and related disorders. Much is known about this disease and it is probably not an overstatement to say that there are more data regarding the molecular and biological events underlying CML than any other human cancer. Nevertheless, this review emphasizes how inadequate these data are in explaining most of the important aspects of this disorder. Thus, if CML is to be used as a model of other cancers, much work remains to be done. PMID- 3332855 TI - Haematological classification of the chronic myeloid leukaemias. AB - Chronic myeloid leukaemia (CML) includes five subtypes, and the term should be used in the same way as the term chronic lymphoid leukaemia to refer to a group of related conditions. The subtypes of CML are: 1. Chronic granulocytic leukaemia (CGL) (95% of all CML; 90% are Ph+, BCR+, 5% are Ph-, BCR+); 2. Juvenile CML (extremely rare; Ph-, BCR- in the few so far examined); 3. Chronic neutrophilic leukaemia (CNL) (extremely rare; Ph-, BCR- in the few so far examined); 4. Chronic myelomonocytic leukaemia (CMML). CMML with low or normal leukocyte counts is classified as a myelodysplastic syndrome; CMML with high leukocyte count is both myelodysplastic and myeloproliferative. Ph-, BCR-; 5. Atypical CML (aCML). Intermediate between CGL and CMML but has distinctive features. Ph-, mostly BCR-. Significance of few reported BCR+ uncertain. Markedly worse survival than CGL and probably worse than CMML. Definition needs refining. Types 2, 3, 4 and 5 account for 5% of all CML. CGL, CMML, aCML and CNL can be diagnosed in the great majority of cases from the morphological profile of presentation peripheral blood films, but high-quality Romanowsky staining is essential. PMID- 3332856 TI - Prognosis in chronic myeloid leukaemia: biology of the disease vs. treatment. AB - CML is best regarded as a benign neoplasm, which regularly transforms into a rapidly fatal malignant one. Survival is determined by the timing of disease transformation. The rate of transformation and death is low initially and increases gradually to a stable annual rate, reached during the third year after diagnosis. This averages 25% per year in large populations of Ph positive patients. Transformation appears to occur randomly; a patient's risk of transformation can be defined, but the time when it will occur cannot be predicted. There is no evidence that conventional antileukaemic therapy changes the risk of transformation; thus, survival is determined principally by the intrinsic biology of the disease. A number of features recorded at the time of diagnosis correlate significantly with survival and can serve as prognostic parameters. Multivariate regression and Cox model analyses can generate hazard ratio formulae which provide quantitative estimates of patients' risk. Several Cox models have been described by different groups, and it is possible that two or more models may describe survival equally well. A four-variable model described by the International CGL Prognosis Study Group in 1984 has recently been tested in a prospective study by the Italian Cooperative Study Group on Chronic Myeloid Leukaemia, and successfully classified patients into three groups with significantly different outcomes. This model produces excellent results in analyses of large patient populations, but is less satisfactory when applied to smaller series. It is likely that current prognostic models can be improved substantially to provide more accurate definition of patient risk over a broader range of hazard ratio values. Such models should prove useful in evaluating therapeutic schedules, selecting patients for investigational or hazardous treatment and making decisions regarding bone marrow transplantation. PMID- 3332857 TI - Cell culture studies in CML. PMID- 3332858 TI - Chromosome abnormalities in CML. AB - The Ph chromosome is the hallmark of CML, where it is found in more than 90% of the cases. Cytogenetically, it usually results from a t(9;22)(q34;q11). The Ph arises in a stem cell and in chronic phase is found in all haematopoietic cell lineages, although it causes only increased granulopoiesis, and sometimes increased thrombopoiesis; furthermore blast crisis may occur in all differentiative patterns of the pluripotent stem cell. Recently, molecular investigations of Ph positive CML cases have revealed a consistent genomic recombination between two genes, BCR on chromosome 22 and the ABL oncogene. The latter is translocated from 9q34, its normal site, to the 22q- or Ph chromosome. This molecular rearrangement expresses a unique 8.5 kb BCR-ABL hybrid mRNA transcript, that encodes an altered BCR-ABL protein of approximately 210 kD with enhanced in vitro tyrosine kinase activity. The breakpoints on chromosome 22q- are clustered in a 5 kb DNA fragment, allowing their study using Southern blot analysis. Cytogenetic variant forms of the Ph translocation involving three or more chromosomes are found in about 5% of the cases. Southern blot and in situ hybridization studies have demonstrated that these variants are cytogenetically more complex than the standard t(9;22) but molecularly they show the same essential genomic recombination. This is also true for a small number of cases of Ph negative CML. Clonal progression, indicated by the presence of clonal, non random chromosome abnormalities, in addition to the Ph is rare during chronic phase but is found in 80% of blast crisis. These additional aberrations may precede BC by weeks or months and have therefore a clear prognostic value. Ph is not restricted to CML, since it is also found in ALL (20% of adult cases) and rarely in AML. Ph in acute leukaemia is cytogenetically indistinguishable from Ph in CML, but molecular studies have shown that in 50% of the cases the breakpoint on chromosome 22 is different from the very consistent and characteristic breakpoint in CML. Nevertheless genomic recombination takes place that results in a novel ABL protein at least in some of the cases. Despite extensive cytogenetic and molecular investigations, the mechanisms underlying the formation of the Ph as well as the pathogenesis of Ph positive CML are still unknown but are now the object of intensive research. PMID- 3332859 TI - The BCR/ABL hybrid gene. AB - A DNA region on chromosome 22, designated M-BCR, contains the chromosomal breakpoint of the Philadelphia (Ph) translocation in all Ph positive CML patients studied to date. M-BCR is part of a gene, BCR, oriented with its 5' end towards the centromere of chromosome 22. All of the CML DNAs analysed have a breakpoint within introns of the BCR gene. As a consequence of the Ph translocation the 3' end of the BCR gene has been translocated to chromosome 9, while the 5' part remains on the Ph chromosome. The remaining BCR sequences act as an acceptor for a chromosome 9 gene, the ABL oncogene: the ABL oncogene is fused in a head-to tail fashion to the chromosome 22 sequences. This genomic configuration results in the transcription of a novel chimeric mRNA consisting of 5' BCR sequences and 3' ABL oncogene sequences. In K562, a cell line derived from a CML patient, and in five CML patients such chimeric BCR/ABL transcripts have been demonstrated. An abnormally sized ABL protein has been detected in the cell line K562 and in leukaemic cells from patients. This protein represents the translational product of the chimeric mRNA. The role of the BCR part of the fusion protein is unknown; it is possible that the BCR moiety could alter the structure of the ABL protein and unmask its tyrosine kinase activity. By analogy with the gag/v-abl polyprotein, the CML-specific BCR/ABL protein might have transforming activity and could play an essential role in the generation and/or maintenance of CML. PMID- 3332860 TI - Effect of pressure applied to the acid-etched enamel on the adhesive strength of the bonding agent. PMID- 3332862 TI - Trial application of integrated metal mesh for the denture base. PMID- 3332861 TI - The adhesion mechanism of dental adhesive resin to the alloy--relationship between Co-Cr alloy surface structure analyzed by ESCA and bonding strength of adhesive resin. PMID- 3332863 TI - Effect of casting machine on nickel-chromium alloy castings for fixed prosthesis. Part 1. Change in tensile strength. PMID- 3332864 TI - Electroencephalographic findings in antiepileptic drug trials: a review and report of 6 studies. AB - A recent survey has shown that the EEG is of doubtful value as an outcome variable in clinical antiepileptic drug (AED) trials. Analysis of findings in 6 trials shows that in only two no consistent effect was seen; that in two power spectral analysis provided additional information to confirm changes in background activity; that in one a close relationship could be established between reduction in frequency of epileptiform discharges and administration of the trial drug (lamotrigine), and that in one, even though no correlation was apparent during use of the AED, there was an increase in frequency of both discharges and seizures on withdrawal (CGP 11952). In general the EEG would appear to be unsuitable as an outcome variable for assessing drug efficacy in AED trials. On the other hand it may give insight into the mode of drug action. Conceivably more efficient use could be made of the EEG if the methodology- including patient selection, consideration of circadian rhythms and of combination AED therapy, and standardized long-term recording--were to be improved and automation and quantification techniques used. PMID- 3332865 TI - CT brain scan and EEG in the diagnosis of adult onset seizures. AB - Incidence of CT abnormalities and their correlation with clinical and EEG features were evaluated in a consecutive series of 202 adult patients with newly diagnosed epileptic seizures. Abnormal CT findings were found in 36% of these patients; the abnormalities consisted of brain tumors (17%), atrophic lesions (11%) and other organic findings (8%) such as arteriovenous malformations. Focal features of seizures, in neurological examination and/or in EEG, correlated significantly with CT abnormalities. The absence of these findings did, however, not exclude the possibility of brain lesions, which in many cases were treatable by surgery. PMID- 3332867 TI - Migraine-epilepsy relationships. PMID- 3332866 TI - Seven day administration of lamotrigine in epilepsy: placebo-controlled add-on trial. AB - A double-blind placebo-controlled trial of 7 days administration of lamotrigine as add-on therapy was performed in 10 patients with frequent therapy-resistant, chiefly partial, seizures. Dosage was adjusted on the basis of estimated half life. Six patients showed a 50% seizure reduction on lamotrigine and two an increase. Side effects (ataxia, dizziness and apathy) occurred in 3 patients, but only at blood levels above 3 micrograms/ml, and were rapidly relieved when the dose was reduced in two. EEG spike counts were significantly reduced on lamotrigine. There was no evidence of interactions with co-medication. PMID- 3332868 TI - [The contribution of the laboratory to the correct usage of antibiotics]. PMID- 3332869 TI - Aminoglycosides and beta-lactams. Different possible kind of interaction during the time between drugs and microorganisms. PMID- 3332870 TI - [Miocamycin: multicenter clinical study in patients with bacterial infections of the upper respiratory tract]. PMID- 3332871 TI - [Scaling and polishing. An essential attitude in periodontics]. PMID- 3332872 TI - Human T-lymphotropic virus type III (HTLV-III). PMID- 3332873 TI - Ring chromosome in a case of acute myelomonocytic leukemia: its significance and a review of the literature. AB - The presence of ring chromosomes is a rare finding in patients with de novo acute nonlymphocytic leukemia (ANLL). In this report we describe the cytogenetic abnormalities, including ring chromosomes, of a 45-year-old white male who had ANLL of the myelomonocytic type (M4). All of the leukemic cells had both a small unidentified ring and a medium-sized ring which was derived from chromosomes 2 and 11, r(2;11)(2p25;11p15q23;2q37). Four different types of rings or other structural abnormalities were derived from this medium-sized ring. A review of the literature indicated that the median survival of ANLL patients with either identified or unidentified ring chromosomes was 5 to 6 months, and that the presence of these cytogenetic abnormalities was related to a poor prognosis. PMID- 3332874 TI - Hypothesis: splenic filtration and the pathogenesis of extramedullary hematopoiesis in agnogenic myeloid metaplasia. PMID- 3332875 TI - Advances in automated blood counting. PMID- 3332876 TI - The use of monoclonal antibodies in the characterization of myeloid leukemias. PMID- 3332877 TI - In memoriam Benjamin Drewinko, M.D., Ph.D (1940-1987). PMID- 3332878 TI - Erythropoietin: current concepts and future prospects. PMID- 3332879 TI - Do pathologic features predict prognosis in diffuse large B-cell lymphoma? AB - We analyzed 47 immunologically confirmed cases of diffuse large B-cell lymphoma (DLBL) to determine whether the histologic type, surface immunoglobulin (Ig) phenotype, or mitotic rate predicted the clinical outcome. All patients were uniformly staged and uniformly treated with one six-drug protocol. Seventeen cases were subclassified as the noncleaved cell type (DLBL-NC), 23 cases as the immunoblastic type (DLBL-IBL), and 7 cases as other follicular center cell (FCC) types (DLBL-O). The predicted two-year actuarial survival for patients with DLBL O (82%) was significantly longer than for those with DLBL-NC (35%; p = 0.05). The immunologic phenotype and mitotic rate also predicted the clinical outcome. The predicted two-year survival for patients with DLBL having a surface IgM phenotype (29%; p = 0.06), and the two-year survival for patients with FCC-derived DLBL (DLBL-NC plus DLBL-O) having a surface IgG phenotype (80%) was significantly longer than for those with a surface IgM phenotype (0%; p = 0.02). Similarly, the two-year survival for patients with DLBL having less than 30 mitoses (68%) was significantly longer than for those having greater than or equal to 30 mitoses per 10 high-power fields (28%; p = 0.01). These findings are considered preliminary, and additional studies of a large number of similar patients are necessary for their confirmation. PMID- 3332880 TI - Cellular and molecular markers of thrombosis. PMID- 3332881 TI - The epidemiology of diseases associated with HTLV-I and HTLV-II. AB - Considerable progress is being made in the understanding of at least two diseases associated with HTLV-I, ATLL and TSP. While laboratory methodology has not yet permitted comparable advances in identifying diseases associated with HTLV-II, if any, it is likely that a greater understanding of this and other retroviruses will result from the increasing focus of attention in this area. As illustrated by a recent meeting on retroviruses in the nervous system, which included discussions on polymyositis and multiple sclerosis as well as TSP, ATLL, and AIDS, the number of diseases associated with retroviruses is likely to increase and, if the applications of research data to the control of malignancies associated with hepatitis B virus and Epstein-Barr virus are applicable, the future for improving control of HTLV-I-associated disease should be quite promising. PMID- 3332882 TI - Lyme disease. AB - Lyme disease is a complex multisystem disorder recognized on three continents, which is epidemic in some regions during spring, summer, and fall seasons. It primarily affects skin, nervous system, heart, and joints. It is an infectious disease caused by a spirochete Borellia burgdorferi, which is transmitted chiefly by Ixodes dammini and pacificus ticks in the United States and Ixodes ricinus in Europe. Diagnosis is based on patient contact with an endemic area, one or more characteristic clinical features, particularly erythema migrans rash, and a positive serologic test for B. burgdorferi infection in the majority of cases. Although infection is the primary cause of the disease, immune mechanisms may play a synergistic role in some manifestations. Prompt diagnosis and treatment are important for full recovery. Treatment with oral tetracycline or penicillin is effective in the earliest stages but late complications require high doses of intravenous penicillin and sometimes corticosteroids. Some late complications are refractory to antibiotic therapy. Antibody appears to be protective in human and experimental studies. PMID- 3332883 TI - Delta agent hepatitis. AB - Since its chance discovery a mere decade ago, the delta agent has been characterized as a novel pathogen that poses the risk of developing into a scourge of modern times. With its unique single-stranded circular RNA, exclusive dependence on HBV for its replication, and characteristic ability to suppress hepatitis B synthesis, the delta agent has emerged as an important global cause of fulminant hepatitis and progressive liver disease. Persons at greatest risk of delta infection are those living in endemic areas and HBsAg-carrier parenteral drug abusers, hemophiliacs, hemodialysis patients, and homosexual men in nonendemic areas. Widespread dissemination appears possible. There is as yet no known effective treatment for established delta infection, and, for the present, clinicians must concentrate on preventing HDV infection by incorporating vigorous use of the hepatitis B vaccine into strategies for preventing HBV infection. PMID- 3332884 TI - New developments in AIDS. AB - At the present time there is no effective therapy for the HIV infection itself, nor for the opportunistic infections, malignancies, immune perturbations, and other manifestations of AIDS. However, as a result of knowledge gained regarding the modes of transmission of HIV, public health officials have made recommendations which, if followed, would slow or even halt further spread of the virus. Thus it is hoped that educational efforts directed at individuals in high risk groups will be effective in stopping transmission of this disease and that ongoing research efforts will soon provide therapeutic agents to cure it or slow its progression. PMID- 3332885 TI - Kawasaki syndrome. AB - Kawasaki syndrome is a recently recognized acute febrile illness of childhood. The etiology is unknown, and diagnosis depends on fulfilling certain clinical criteria. The significance of the disorder rests primarily on possible cardiovascular involvement, which occurs in about 50 per cent of patients. At least 20 per cent develop coronary artery aneurysms. Therapy remains nonspecific and incompletely effective. PMID- 3332886 TI - Cat scratch disease. AB - In summary, CSD is a relatively common cause of localized lymphadenopathy, with 80 per cent of cases occurring in children. This self-limited infection is caused by a small pleomorphic bacillus that has been identified in ocular granuloma, skin, and lymph node specimens. Unusual manifestations of the disease such as the oculoglandular disease of Parinaud, encephalopathy, or severe systemic disease occur in about ten per cent of patients. Management consists of symptomatic treatment and occasionally aspiration of a node that suppurates. The disease usually resolves spontaneously in 2 to 4 months. PMID- 3332887 TI - Legionella infections. AB - Legionnaires' disease is a distinct clinical entity caused by Legionella pneumophila. Following an epidemic of pneumonia in Philadelphia in 1976, it was found that the bacterium had in fact been first isolated in 1947. Other species of Legionella have been identified, many of which are indistinguishable from L. pneumophila infection. Legionella species also cause extrapulmonary infections and a mild nonpneumonic form of disease known in its epidemic form as Pontiac Fever. PMID- 3332888 TI - New causes of pneumonia, meningitis, and disseminated infections associated with immersion. AB - Immersion in water increases the risk of infection by certain microorganisms, including bacteria, fungi, and parasites. Physicians should be aware of this relationship because many of these infections are not normally encountered except in association with water exposure. The morbidity and mortality associated with these infections may be substantial. Clinical features of pneumonia, disseminated infection, and central nervous system infections are detailed. PMID- 3332889 TI - Intoxications from the seas: ciguatera, scombroid, and paralytic shellfish poisoning. AB - Sporadic cases and outbreaks of intoxications borne by fish and shellfish have increased in frequency during recent years. Ciguatera, scombroid, and paralytic shellfish poisoning account for nearly 16 per cent of all reported foodborne outbreaks of disease in the United States. Fishborne ciguatera and paralytic shellfish poisoning are characterized by gastrointestinal and neuromuscular manifestations attributable to toxins of dinoflagellates. These toxins impair sodium transport in cell membranes. Treatment is primarily supportive. Scombroid fish intoxication resembles histamine poisoning and may be treated effectively with antihistamines or cimetidine. Prevention of these intoxications at present depends upon avoidance of potential vectors. PMID- 3332890 TI - Nontuberculous mycobacteria and water: a love affair with increasing clinical importance. AB - Water serves as a major reservoir for the environmental mycobacteria. Many cases of cutaneous mycobacterial disease result from water exposure. The current theory of the pathogenesis of M. avium complex lung disease involves inhalation of organisms aerosolized from surface water. Disseminated M. avium disease in AIDS invariably involves the gastrointestinal tract strongly suggesting that contaminated water could serve as the disease source for this increasingly important disease. PMID- 3332891 TI - Localized and systemic infection due to Vibrio species. AB - Many important species have been added to the genus Vibrio in the past several years. Vibrios have been associated with a wide variety of clinical syndromes ranging from mild gastroenteritis to life-threatening cellulitis. Most Vibrio infections follow consumption of raw shellfish or exposure to sea water. Although much has been learned about these organisms in the past several years, additional information is needed concerning pathogenesis, diagnosis, treatment, and prevention of Vibrio infections. PMID- 3332892 TI - Amphotericin B dosage for disseminated candidiasis in premature infants. AB - Amphotericin B (Amp-B) serum concentrations were determined in five infants with disseminated candidiasis. All patients had positive blood cultures for Candida and one patient had Candida albicans meningitis. Amp-B sterilized the blood and the cerebrospinal fluid within four to nine days. Total doses of Amp-B varied from 11.6-62.3 mg. There was no laboratory or clinical evidence of renal toxicity. Two infants died of causes unrelated to disseminated candidiasis. Disseminated candidiasis in premature infants was treated successfully with 0.5 mg/kg doses of Amp-B, but further studies with more evaluable cases are needed to confirm the correct dose. PMID- 3332893 TI - Prolapsing amniotic membranes: detection, sonographic appearance, and management. AB - Seventeen cases of prolapse of the amniotic membranes through a partially dilated endocervical canal are presented. Most of the patients had no prior history of incompetent cervix and less than half had either a therapeutic or spontaneous abortion. The prolapsed amniotic membranes are accompanied by uterine contractions and usually occur in the late second or early third trimester of pregnancy. Ultrasound was useful in confirming clinical findings, defining the extent of the prolapsed amniotic membranes, determining fetal viability, and demonstrating contents of the amniotic membranes. Tocolytics, abdominal amniocentesis, and cervical cerclage were of little benefit in preventing immediate delivery. Of the 17 patients, ten were live births and eight were stillbirths or immediate death due to prematurity. PMID- 3332894 TI - Management of chronic hypertension in pregnant patients. AB - Chronic hypertension is a medical disorder associated with increased maternal and neonatal mortality and morbidity. The disease is also associated with superimposed pre-eclampsia and requires consultation. The antihypertensive therapy associated with the best results remains to be clarified. The literature, however, substantiates the use of a multidisciplinary unit to manage these patients in order to maximize outcomes. PMID- 3332895 TI - Topics in perinatal ultrasonography. Caudal regression syndrome. PMID- 3332896 TI - Neonatal radiologic casebook. Group B streptococcal infection/cerebral necrosis. PMID- 3332897 TI - [The influence of morphological factor of abutments on the retentive force of cast clasps]. PMID- 3332898 TI - [Suppression of remaining resin on tooth surfaces in debonding of orthodontic brackets. Part 1. Destruction behaviors of adhesion system]. PMID- 3332899 TI - [Suppression of remaining resin on the tooth surfaces in debonding of orthodontic brackets. Part 2. Correlation between bracket base form design and remaining resin on the tooth surfaces]. PMID- 3332900 TI - [Central projection of the cutaneous branches of the rat cervical plexus, the transverse colli, the lesser occipital and the great auricular. A study using transganglionic transport of horseradish peroxidase]. PMID- 3332901 TI - Agarose encapsulation of islets of Langerhans: reduced toxicity in vitro. AB - The physical and chemical properties of agarose have been exploited for encapsulation of islets of Langerhans. Formation of microcapsules by extrusion of a hydrophilic polymer (agarose) into a hydrophobic solution created an interface to which an immunoprotective membrane could be polymerized. The substances and procedure used were devoid of cellular toxicity. Islet function in vitro was found to be normal. PMID- 3332902 TI - [Gingival recession: its prevention and treatment]. PMID- 3332903 TI - The blood-brain barrier: interacters between endothelial cells and astrocytes. PMID- 3332904 TI - Development of the mammalian visual system. PMID- 3332905 TI - Molecular approaches to study of surfactant protein structure and function. PMID- 3332906 TI - Transgenic mice in the study of development. PMID- 3332907 TI - Role of extracellular matrix in morphogenesis. PMID- 3332908 TI - Analysis of the plasmids of Escherichia coli O148:H28 from travellers with diarrhea. AB - 98 Escherichia coli strains of serotype O148:H28 isolated from diarrheal patients from 10 Asian countries and Mexico at Osaka Airport Quarantine were analyzed for enterotoxigenicity and plasmid profile. They were classified into three groups. The first group contained 44 strains that were non-enterotoxigenic and carried 3.9 kb and 50 kb non-enterotoxin plasmids. The second group contained 9 strains that produced LT and ST. They carried a 45 kb enterotoxin plasmid, and 4.6 kb and 9.2 kb non-enterotoxin plasmids. The third group contained 45 strains that produced ST. They carried a 40 kb enterotoxin plasmid, and non-enterotoxin plasmids other than 3.9 kb, 4.6 kb, 9.2 kb and 50 kb. Southern blot hybridization demonstrated that all the non-enterotoxin or enterotoxin plasmids carried by the strains of the same group were identical or similar. These results suggested that the 98 E. coli strains with O148:H28 serotype were derived from three clones, and that the individual strains among each group were derived from a single clonal strain. PMID- 3332909 TI - Response of tissue-cultured cynomolgus monkey kidney cells to botulinum C2 toxin. AB - C2 toxin (C2T) elaborated by Clostridium botulinum types C and D is composed of two nonlinked protein components, designated components I and II. The toxin, a mixture of untrypsinized component I and trypsinized component II, induced marked morphological changes of tissue-cultured cynomolgus monkey kidney cells; the characteristic response of the cells to the toxin was rounding, which increased proportionally to log dose of the toxin. The components alone and a combination of untrypsinized components I and II showed little activity. The rounding of the cultured cells was not accompanied by inhibition of protein and nucleic acid syntheses of the cells, although the rounded cells ultimately lost viability. Immunofluorescence studies showed that component II, either trypsinized or untrypsinized, bound to the cell surface, whereas component I bound to the cells only in the presence of trypsinized component II. The present results support the previously proposed idea concerning the mode of action of C2T, that components I and II of C2T act together as a molecule with dual functions; component II as the recognizer of the receptor site on the cell surface membranes and component I as the effector in the cytoplasm by preferential inactivation of cytoskeletal actin, which results in alteration of cell morphology, and subsequently in cellular damage. PMID- 3332911 TI - Pregnancy-associated immune suppression: risks and mechanisms. PMID- 3332910 TI - Evidence for group A-related M protein genes in human but not animal-associated group G streptococcal pathogens. AB - Group G streptococci have on their surface antiphagocytic M protein-like antigens. To determine if these organisms have genes similar to the M protein genes of Streptococcus pyogenes (group A), DNA from independent group G isolates of human and animal origin were tested for homology to probes representing sequences encoding the carboxy-terminus and leader peptide of the type 12 M protein (M12) of group A streptococci. All eight human-associated group G strains tested had DNA homologous to the carboxy-terminal probe. Six of these strains also had DNA that hybridized with the leader peptide probe. Using probes representing the group A M12 gene (emm12) and adjacent 5' sequences, we found that one of these strains, known to produce an M12 antigen, had a nearly complete duplication of the group A emm12 gene, differing only in 0.26 kb of sequence at the 5' end. The other human-associated strains did not hybridize with emm12 specific sequences. None of the group G strains had homology to 5' proximal sequences thought to be associated with group A emm12 regulation, but all the human-associated strains had DNA homology to a 1.5 kb DNA segment which mapped 2.5 kb upstream of the emm12 gene in group A streptococci. None of the twelve animal-associated strains tested hybridized with any of the probes used in this study. These results suggest that human but not animal-associated group G isolates have group A-related M protein genes. We propose that expression of these genes are critical for infection of the human host and that group A and G shared upstream sequences could encode additional virulence factors. PMID- 3332912 TI - Distribution and properties of the mannose-resistant hemagglutinin produced by Salmonella species. AB - Presence or absence of mannose-resistant hemagglutination (MRHA) or sheep erythrocytes by Salmonella species was found to be consistent within most serotypes tested and did not correlate with O-antigen. Broad-host-range serotypes including S. typhimurium and S. enteritidis produced MRHA while host-specific serotypes including S. typhi, S. dublin, and S. gallinarum were MRHA-negative. MRHA produced by S. typhimurium was soluble, heat-stable, and not inhibited by any of eleven carbohydrates tested. Further investigation of MRHA may provide insight into mechanisms of Salmonella pathogenesis. PMID- 3332913 TI - Historical review: abnormal movements associated with epidemic encephalitis lethargica. PMID- 3332915 TI - Sixty-five-year index of Physical Therapy. PMID- 3332914 TI - A double-blind evaluation of ciladopa in Parkinson's disease. AB - We evaluated 32 patients with Parkinson's disease in a double-blind, parallel group, placebo-controlled study with ciladopa (a troponylpiperazine derivative). The dosages administered were 5 mg b.i.d. and 15 mg b.i.d. Significant improvement was found in the gait scores and in the total disability scores in the high dose group (p less than 0.05). In addition, there was a trend toward improvement, though not significant, in the bradykinesia and rigidity scores in the high dose group and in the disability scores in the low dose group. Four patients in the low dose group and five patients in the high dose group decreased their Sinemet doses while no patients increased their Sinemet dose. There were no adverse effects observed in this study. These findings suggest that ciladopa may be an efficacious agent in Parkinson's disease. The low incidence of adverse effects with this agent suggests that higher doses may be utilized and may prove to be more effective. PMID- 3332917 TI - Platinum antitumour agents. PMID- 3332916 TI - Ricin: cytotoxicity, biosynthesis and use in immunoconjugates. PMID- 3332918 TI - Towards cannabinoid drugs. PMID- 3332919 TI - Calcium channel blocking drugs. PMID- 3332920 TI - Molybdenum hydroxylases: biological distribution and substrate-inhibitor specificity. PMID- 3332921 TI - [Krapinske Toplice--from a health spa to a modern hospital for rheumatic diseases and rehabilitation]. PMID- 3332922 TI - [Clinical effects of the infusion of dobutamine and amrinone in patients with refractory cardiac insufficiency]. PMID- 3332923 TI - [Clinical analysis of a series of 69 definitive cases of Jakob-Creutzfeldt disease occurring in Chile between 1960 and 1985]. PMID- 3332925 TI - [Use of intravenous cyclosporin in the treatment of episodes of irreversible rejection in renal transplantation]. PMID- 3332926 TI - [Sodium and essential arterial hypertension. What is known, what is searched for and what is applicable to clinical practice]. PMID- 3332924 TI - [A single dose of sulfamethoxazole-trimethoprim vs. a 7-day course of nitrofurantoin in the treatment of acute non-complicated urinary tract infection in women]. PMID- 3332927 TI - [Colloids and crystalloids: a critical re-evaluation]. PMID- 3332928 TI - [Psychiatric indications of drugs used in clinical practice]. PMID- 3332929 TI - [Use of monoclonal antibodies in the diagnosis and treatment of infection in immunocompromised patients]. PMID- 3332930 TI - [Immunology in myocardial infarct and acute coronary failure. Overview of findings on the problem]. PMID- 3332931 TI - [Clinical experience with the use of the echo-Doppler method in lesions in the carotid vascular bed]. PMID- 3332932 TI - The nature of the final oxidative step in the aromatization sequence. PMID- 3332933 TI - Metabolism of 19-methyl substituted steroids and a proposal for the third aromatase monooxygenation. AB - The article summarizes the results of recent studies on the metabolism of 10 ethylestr-4-ene-3,17-dione, 10-[(1R)-1-hydroxyethyl]-, and 10-[(1S)-1 hydroxyethyl]estr-4-ene-3,17-dione, in placenta. These compounds are the 19 methyl analogs of androstenedione, 19-hydroxyandrostenedione, and 19 oxoandrostenedione, respectively. No conversion of 10-ethylestr-4-ene-3,17-dione to either estrogens or oxygenated metabolites was detected. Both 10-[(1R)-1 hydroxyethyl]- and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3,17-dione were oxygenated to 10-(1,1-dihydroxyethyl)estr-4-ene-3,17-dione and isolated following in situ dehydration as 10-acetylestr-4-ene-3,17-dione. Evidence for the involvement of aromatase in these conversions is discussed. No conversion of 10-acetylestr-4-ene 3,17-dione to either estrogens or other oxygenated products was detected. These results lead us to propose a new mechanism for the third aromatase monooxygenation. We propose that the third oxygenation is initiated by 1 beta hydrogen abstraction at C1 of 19,19-dihydroxyandrostenedione, followed by homolytic cleavage of the C10-C19 bond with concurrent formation of a delta 1(10),4-3-ketosteroid and a C19 carbon radical, and terminated by oxygen rebound at C19. PMID- 3332934 TI - Intratesticular site of aromatase activity and possible function of testicular estradiol. PMID- 3332935 TI - The potential significance of aromatase in the etiology and treatment of prostatic disease. AB - Prior to the present conference on aromatase, reports in the literature on prostatic aromatase have been scattered over time, few in number, and the results have been widely divergent. Moreover, several participants at this conference have reported unpublished data that failed to detect the existence of androgen aromatase in the prostate of man and other species. While papers and posters presented at this conference have added new information to this field, there would still appear to be no consensus as to the biological significance, if any, of the putative androgen aromatase system or the practical importance of inhibitors of prostatic and/or peripheral aromatase as a treatment modality for benign prostatic hyperplasia (BPH). Thus, it would be difficult to predict at this time the ultimate impact which current prostatic aromatase investigations will eventually have on our understanding and treatment of prostatic disease. To summarize the status of our current understanding of aromatase as it relates to prostatic function and disease, it would be safe to note that this field is virtually wide open for researchers to explore, both in terms of the future role that aromatase inhibitors may have in clinical investigations and in terms of the functional significance of aromatase, if any, in the normal prostate as well as in the pathogenesis of BPH and prostate cancer. Clearly, the widely divergent results currently available in the literature must reflect, in part, differences in methodology, anatomy, tissue types, the relative amounts of stroma and epithelium in specimens analyzed, the cellular and tissular (normal, BPH, and carcinomatous) heterogeneity encountered in clinical specimens, and the pharmacologic features of aromatase inhibitors tested. PMID- 3332936 TI - Estrogen formation in the mammalian brain: possible role of aromatase in sexual differentiation of the hippocampus and neocortex. AB - Recent studies suggest that sex differences in cognitive function may involve effects of circulating androgens on the developing cerebral cortex and hippocampus. The mechanism of these effects is not understood. In rhesus monkeys, aromatase activity is present in the hippocampus and several areas of the cerebral cortex during late fetal and early postnatal life. Similarly, work in rats and mice indicates that the hippocampus and cerebral cortex may be capable of estrogen biosynthesis during early development. These results are consistent with the hypothesis that the actions of androgens on the developing cerebral cortex and hippocampus may involve local estrogen-mediated effects similar to those responsible for differentiation of the hypothalamic mechanisms controlling reproductive function. PMID- 3332938 TI - The distribution and regulation of aromatase activity in the central nervous system. AB - Our data demonstrate that androgen-dependent AA is found in areas of the brain that are essential for the neuroendocrine control of gonadotropin secretion and sexual behavior. However, until we know more about the neurons that contain AA, e.g., whether they are peptidergic or catecholaminergic, we can not speculate about the neuronal functions that depend on local estrogen formation. In fact, the association of AA with neurons and not glia has only recently been demonstrated. That estrogens and androgens synergize in the regulation of various neuroendocrine functions has been known for many years, but an explanation of the synergism at the cellular level was not available. One explanation for this synergism may lie in our recent observation that the administration of exogenous estradiol to castrated rats increases androgen-receptor concentrations in specific brain nuclei. Perhaps locally formed estrogens work in a similar fashion to regulate androgen receptors in the brain of the intact male. PMID- 3332937 TI - The role of estrogen as a parahormone in brain and pituitary. AB - Where aromatase and estrogen receptors are co-localized in brain and pituitary, estrogen functions as a parahormone, and estrogen levels which determine the occurrence or magnitude of a response are those in close proximity to targets. Teleost fish, a vertebrate group characterized by exceptionally high aromatase in neuroendocrine tissues, are technically advantageous animal models for studying the cellular location of aromatase, natural changes correlated with seasonal reproductive cycles, substrate-dependence of the reaction, steroid induction of enzyme activity, and possible non-genomic actions of estrogen on cultured neurons. In addition, characterization of steroid receptors reveals that the androgen receptor, like aromatase, is present in unusually high concentrations (10- to 100-fold higher than in mammalian brain). Since androgen receptors and aromatase both utilize testosterone as a ligand, their high abundance in teleost brain may be the consequence of a functional interdependence during evolution, although the primary causal factor is unknown. These studies illustrate the usefulness of unconventional species and a comparative approach for obtaining new insights into brain-steroid interactions. PMID- 3332939 TI - Aromatase activity in the breast and other peripheral tissues and its therapeutic regulation. AB - Studies using [3H]androstenedione (A) demonstrated that this substrate can be aromatized to estrone (E1) in homogenates of breast carcinoma tissue and breast adipose tissue, in breast carcinoma and breast adipose stromal cells in culture, and in cultured adipose stromal cells from sites remote from the tumor. Using cultured breast carcinoma cells, it was shown that estrogen formation was stimulated by cortisol (10(-6) M) and inhibited by endogenous 5 alpha-reduced androgens: 5 alpha-androstene-dione greater than androsterone greater than dihydrotestosterone greater than epiandrosterone greater than 3 alpha- and 3 beta androstanediol. It was also shown that 19-nortestosterone and 19 norandrostenedione (10(-6) M) inhibited E1 formation by 80%. Progesterone (10(-6) M) had no effect on aromatase activity, while the progestational agent R5020 (10( 6) M) caused a 70% inhibition. These studies emphasize that a variety of compounds can influence aromatase activity and that drugs which are used as aromatase inhibitors in patients with breast carcinoma may have multiple sites of action. PMID- 3332940 TI - Potential clinical role of new aromatase inhibitors. PMID- 3332941 TI - [Theoretical and clinical data regarding the endodontic treatment of periapical cysts]. PMID- 3332942 TI - [Design of partial dentures]. PMID- 3332943 TI - [Iatrogenic injuries coming from fixed prostheses]. PMID- 3332944 TI - [Bruxism: a review of the recent literature]. PMID- 3332945 TI - [Centric relation - A point of controversy. Historical background and present status]. PMID- 3332946 TI - [Damages to the soft tissues of the oral cavity by dental prostheses]. PMID- 3332948 TI - [Myxoma of the jaws. A clinicopathological study of ten cases]. PMID- 3332947 TI - [The problem of the reduction of the residual ridge from the prosthodontic viewpoint]. PMID- 3332949 TI - [Clinical significance and differential diagnosis of median rhomboid glossitis]. PMID- 3332950 TI - [Desquamative gingivitis]. PMID- 3332951 TI - [A clinical study of guanfacine in the treatment of arterial hypertension]. PMID- 3332952 TI - [Hepatic amebiasis. Apropos of 3 cases]. PMID- 3332953 TI - [Mycotic endocarditis. Apropos of 2 cases and a review of the literature]. PMID- 3332954 TI - [Sex hormones and the metabolism of carbohydrates]. PMID- 3332955 TI - [Recent data on the microbiology of broncho-pulmonary cancer]. PMID- 3332956 TI - [Experience of 154 uretero-neo-cystostomies]. PMID- 3332957 TI - [Professor Mohamed Kassab]. PMID- 3332959 TI - [Cavernous hemangioma of the parotid gland in adults (apropos of a case)]. PMID- 3332958 TI - [Use of Doppler pulse in the qualitative and quantitative diagnosis of aortic, mitral and tricuspid valve insufficiency. Angiographic comparison of the results]. PMID- 3332960 TI - Cell division age dependency of meiosis in an apomictic variant of Saccharomyces cerevisiae. AB - The cell division age dependency of sporulation was investigated in a diploid strain of Saccharomyces cerevisiae (19el) which undergoes a single equational nuclear division during sporulation with consequent formation of asci containing two uninucleate diploid spores (apomictic dyads). Under modified nutritional conditions which partially restore meiosis and hence normal tetrad formation, newly formed (age 0) daughter cells were observed to be capable of formation of apomictic dyads but not of meiotic tetrads. Even under conditions in which only apomictic dyads developed, approximately 20% of the asci resulted from differentiation of newborn 'inexperienced' cells. Thus, the data indicated production of at least one bud to be a prerequisite for meiosis but not for apomixis; however, occurrence of at least one complete mitotic cell division cycle was evidently insufficient for the morphogenetic switch from diploid to haploid spore formation, since older cells bearing several bud scars often underwent apomictic dyad development, and some produced no spores. PMID- 3332961 TI - Identification of polypeptides of the carbon metabolism machinery on the two dimensional protein map of Saccharomyces cerevisiae. Location of 23 additional polypeptides. AB - Using a modification of the basic two-dimensional polyacrylamide gel electrophoresis technique, we have undertaken a systematic identification of the polypeptides of the protein map of Saccharomyces cerevisiae corresponding to components of the carbon metabolism machinery. To the previous location of nine glycolytic enzyme polypeptides on the yeast protein map we add the location of 23 polypeptides. Ten of them were identified as corresponding to cytoplasmic enzymes of the carbon metabolism machinery and 13 were characterized as mitochondrial proteins. The criteria used to establish the identification of these polypeptides spots include migration with purified proteins, immunodetection, overproduction by plasmid-carrying strains and physiological behaviour. PMID- 3332963 TI - Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation of the MAK16 gene and analysis of an adjacent gene essential for growth at low temperatures. AB - MAK16 is an essential gene on chromosome I defined by the thermosensitive lethal mak16-1 mutation. MAK16 is also necessary for M double-stranded RNA replication at the permissive temperature for cell growth. As part of an effort to clone all the DNA from chromosome I, plasmids that complemented both the temperature sensitive growth defect, and the M1 replication defects of mak16-1 strains were isolated from a plasmid YCp50: Saccharomyces cerevisiae recombinant DNA library. The two plasmids analysed contained overlapping inserts that hybridized proportionally to strains carrying different dosages of chromosome I. Furthermore, integration of a fragment of one of these clones occurred at a site linked to ade 1, confirming that this clone was derived from the appropriate region of chromosome I. An open reading frame adjacent to MAK16 potentially coding for a 468 amino acid protein was defined by sequence analysis. 185 amino acids of this open reading frame were replaced with a 1.2 kb fragment carrying the S. cerevisiae URA3 gene by a one-step gene disruption. The resulting strains grew at a rate indistinguishable from the wild type at 20 degrees C, 30 degrees C, or 37 degrees C, but could not grow at 8 degrees C. The deleted region is thus essential only at 8 degrees C, and we name this gene LTE1 (low temperature essential). PMID- 3332962 TI - Biochemical estimation of hepatitis B surface antigen in recombinant yeast. AB - Purified recombinant hepatitis B surface antigen separated on polyacrylamide gels in the presence of sodium dodecyl sulphate has a very low staining index with Coomassie blue relative to a number of standard proteins. In contrast the protein stains better than average with silver nitrate. This property has been used to develop a semi-quantitative method of estimation of recombinant surface antigen in extracts of Saccharomyces cerevisiae producing this protein. The method can be used to follow purification protocols. It is quick, simple and since it measures the surface antigen biochemically, is independent of the aggregation state or conformation of the protein, a factor which can affect enzyme-linked immunoassays which rely on antigen-antibody interactions. PMID- 3332964 TI - Analysis of DNA sequences homologous with the ARS core consensus in Saccharomyces cerevisiae. AB - We have previously identified an autonomously replicating segment (ARS) near the 3' end of the histone H4 gene at the copy-I H3-H4 locus. We have now searched for additional autonomously replicating segments and sequences homologous with the ARS core consensus sequence near the copy-II histone H4 gene and both of the histone H3 genes. No new ARS elements were identified by functional cloning assays. However, several matches to the ARS core consensus element were found within the DNA sequences of the copy-I and copy-II genes. An exact match to the ARS core consensus was identified in the region downstream from the copy-I histone H3 gene and a set of sequences with weak homology was also located within the copy-II region. However, restriction fragments including these sequences did not demonstrate ARS activity on a plasmid in transformed cells. PMID- 3332965 TI - Specificity of DNA uptake during whole cell transformation of S. cerevisiae. AB - We have studied the mechanism of DNA transformation of whole yeast cells in Saccharomyces cerevisiae with particular emphasis on the role of the cell wall complex in DNA uptake. Two new aspects of the process have been investigated in order to evaluate its specificity. Such aspects are: (i) effect of monovalent vs. divalent cations during incubation with the transforming DNA and (ii) timing of DNA adsorption and uptake. We found that the specificity for cation requirement is a strain-dependent characteristic influenced by the presence of transforming DNA in the cell suspension. This finding is supported by reports from several laboratories that some yeast strains show mutually exclusive transformability with monovalent vs. divalent cations. While irreversible adsorption of plasmid DNA molecules is induced by both heat shock and polyethylene-glycol (PEG), DNA uptake seems to occur only after the removal of PEG. In the course of this study we have developed a new, alternative method of whole cell DNA transformation with CaCl2 able to transform strains that do not respond to other methods. PMID- 3332966 TI - Artifactual immunofluorescent labelling in yeast, demonstrated by affinity purification of antibody. AB - In the course of making antibodies against various yeast (S. cerevisiae) proteins, we have noted that it is common to observe reactivity of rabbit sera with a number of extraneous bands on Western transfers of yeast proteins. The pattern of reactive bands can change within a period of weeks, even when the rabbit has not been injected with antigen. A simple method of affinity purification, using antigen bound to nitrocellulose, is employed to remove the reactivity with these extraneous bands from immune sera. The importance of affinity purification is demonstrated by our attempts to immunolocalize a 55 kd yeast protein (p55). Immune serum stains yeast cells to give a striking pattern of spots and blotches not seen with preimmune serum. However, affinity purification of anti-p55 antibody shows that this pattern is not due to staining by anti-p55 antibody; rather the pattern is due to staining left in the serum depleted of anti-p55 antibody. PMID- 3332967 TI - Analysis of DNA double strand breakage and repair using orthogonal field alternation gel electrophoresis. AB - Orthogonal field alternation gel electrophoresis (OFAGE) allows separation of DNA molecules in the size range of 200 kb to 3000 kb. These sizes encompass the chromosome sizes of the genome of Saccharomyces cerevisiae. Using this technique, we have found that yeast cells exposed to X-rays generate a smear of DNA fragments corresponding to the products of random, independent double strand breaks, and that the bands corresponding to unbroken chromosomes decrease in intensity in direct proportion to chromosome size. If exposed wild type cells are permitted time to repair (5 h at 30 degrees C on YEPD), the fragments partially disappear and the chromosome bands reappear, although at less than normal intensity. In certain radiation-sensitive mutants (rad51, rad52 and rad54), the fragment smear appears following X-ray exposure but no repair of broken chromosomes occurs. In fact, loss of the fragments occurs; this could appear as partial repair using other procedures. PMID- 3332968 TI - Proliferation of microbodies in Saccharomyces cerevisiae. AB - The development of microbodies in the yeast Saccharomyces cerevisiae was studied in response to different conditions of growth. Various strains of S. cerevisiae were investigated, using cells from the exponential growth phase on glucose as an inoculum in all transfer experiments. Electron microscopy, including serial sectioning, revealed that these cells generally contained one to four small microbodies which were localized in the vicinity of the cell wall and characterized by the presence of catalase. Transfer of these glucose-grown cells into media supplemented with various compounds known to induce microbody proliferation in other yeasts--i.e. uric acid, alkylated amines, amino acids, C2 compounds such as ethanol or acetate, in the presence or absence of compounds that induce oxygen radical formation--did not result in a significant change in the number of microbody profiles observed. Marked microbody proliferation was, however, observed after a shift of cells into media containing oleic acid and was associated with the induction of activities of beta-oxidation enzymes. In addition, catalase and isocitrate lyase were present in enhanced levels. Kinetic experiments suggested that these microbodies developed from those originally present in the inoculum cells. In thin sections up to 14 microbody profiles were occasionally observed, often present in small clusters. Their ultimate volume fraction amounted to 8-10% of the cytoplasmic volume. PMID- 3332969 TI - Tryptophan accumulation in Saccharomyces cerevisiae under the influence of an artificial yeast TRP gene cluster. AB - Plasmid pME559, carrying all five yeast TRP genes, was constructed. This plasmid is a yeast/Escherichia coli shuttle vector based on pBR322 and 2 micron-DNA sequences derived from plasmid pJDB207. We studied in yeast (i) the stability of the plasmid under selective and non-selective conditions, (ii) expression of all five TRP genes and (iii) tryptophan accumulation in yeast transformants. These studies were conducted in comparison with an earlier construction, pME554, which differs from plasmid pME559 in the expression of the TRP1 gene and which carries the TRP2 wild type instead of the TRP2fbr mutant allele. For stable maintenance of the plasmids in yeast a selection was necessary. Plasmid pME559 displayed normal expression of all TRP genes, and enzyme levels on average 23-fold higher than in the wild type strain were found. In comparison, the maximal tryptophan flux observed in such a plasmid-carrying strain was about ten-fold higher than the maximal flux capacity in the wild type strain. PMID- 3332970 TI - Yeast telomeres: the end of the chromosome story? PMID- 3332971 TI - Overexpression of the RAD2 gene of S. cerevisiae: identification and preliminary characterization of Rad2 protein. AB - The cloned RAD2 gene of S. cerevisiae was tailored into regulatable expression vectors for overexpression of Rad2 protein in E. coli and in yeast. In E. coli both Rad2/beta-galactosidase fusion protein and native Rad2 protein are insoluble, but are extractable with 1% Sarkosyl. In yeast some of the overexpressed native Rad2 protein is also insoluble; however, soluble protein is readily detected by immunoblotting with Rad2-specific antibodies. All forms of the protein detected in transformed or untransformed yeast cells and the insoluble species in E. coli migrate in denaturing polyacrylamide gels with an apparent molecular weight considerably larger than the size predicted from the sequence of the RAD2 coding region. This property is not the result of post translational glycosylation detectable by binding of concanavalin A, or of phosphorylation of the protein. Overexpression of the RAD2 gene is toxic to yeast. Transformed yeast cells grow much more slowly than untransformed controls and when yeast transformants are serially propagated cultures show considerably colony heterogeneity and concomitant selection for rapidly growing variants which express less Rad2 protein. Antisera raised against Rad2/beta-galactosidase fusion protein expressed in E. coli do not cross-react with Rad1, Rad3 or Rad10 protein in crude extracts of yeast, nor with purified E. coli UvrA, UvrB or UvrC proteins. PMID- 3332972 TI - Expression of two Trichoderma reesei endoglucanases in the yeast Saccharomyces cerevisiae. AB - The cDNA copies of the two endo-beta-1,4-glucanase genes, egl1 and egl3, from the filamentous fungus Trichoderma reesei were expressed in yeast Saccharomyces cerevisiae under the control of the yeast phosphoglycerate kinase gene promoter. Active EGI and EGIII enzyme was produced and secreted by yeast into the growth medium. The recombinant EGI enzyme was larger and more heterogeneous in size than the native enzyme secreted by Trichoderma, due to differences in the extent of N glycosylation between these two organisms. The morphology of the yeast cells producing EGI or EGIII was clearly different from control strain. PMID- 3332973 TI - Yeast centromeres. AB - Significant progress has been made toward understanding the roles played by conserved centromere DNA sequences in both mitotic and meiotic chromosome segregation. We are just beginning to formulate a picture of what a yeast kinetochore actually looks like and what components other than CEN DNA are necessary for function. In the next few years some of the genes encoding structural components of the kinetochore, and perhaps some involved in regulation of kinetochore function, will be cloned. Work is already in progress to isolate and characterize the proteins necessary for the assembly, maintenance and function of this amazing biological structure. PMID- 3332974 TI - Yeast flocculation: kinetics and collision theory. AB - Flocculent yeast cells have an absolute requirement for mechanical energy input in order for flocculation to occur. Flocculation is arrested by cessation of energy input. The initial rate of flocculation increases as the square of the cell concentration. There is a minimum shaking speed to initiate flocculation and thereafter the initial rate of flocculation increases exponentially with the shaking speed. The minimum shaking speed for flocculation to occur increases with pH value. Activation energy for flocculation, derived from Arrhenius-like plots, varies with pH value. We propose that activation energy is required to overcome mutual repulsion between charged yeast cells and allow flocculent bonds to be formed. PMID- 3332975 TI - Ethanol and the fluidity of the yeast plasma membrane. AB - Evidence is presented for an exponential increase in yeast plasma membrane fluidity (as measured by passive permeability to acetic acid) with ethanol concentration. The role of adaptation of yeast cells to ethanol can be seen in the existence of a threshold concentration before the onset of an observed fluidizing effect. The physiological state of the yeast cells is also demonstrated to influence the sensitivity of the membrane to fluidization by ethanol. On the basis of these results, the concept that increased fluidity is an adaptive response conferring ethanol tolerance is disputed. An alternative hypothesis, namely that the observed increase in fluidity is the net result of a number of more fundamental changes, is presented to explain the observed effects. PMID- 3332976 TI - Mapping of the Saccharomyces cerevisiae CDC3, CDC25, and CDC42 genes to chromosome XII by chromosome blotting and tetrad analysis. AB - CDC3, CDC25 and CDC42 were localized to chromosome XII by hybridizing the cloned genes to Southern blots of chromosomes separated by orthogonal-field-alternation gel electrophoresis. Meiotic tetrad analyses further localized these genes to the region distal to the RDN1 locus on the right arm of the chromosome. The STE11 gene, which had previously been mapped to chromosome XII (Chaleff and Tatchell, 1985), was found to be tightly linked to ILV5. The data suggest a map order of CEN12-RDN1-CDC42-(CDC25-CDC3)-(ILV5- STE11)-URA4. Certain oddities of the data set raise the possibility that there may be constraints on the patterns of recombination in this region of chromosome XII. PMID- 3332977 TI - Effects of yeast suspension density on the accumulation ratio of transported solutes. AB - The previously described effect of cell suspension density on metabolic and transport phenomena in yeast, apparently caused by inhibition by dissolved carbon dioxide, is also observed with the accumulation ratio of both sugars and amino acids where not only a kinetic but also a energetic factor comes into play. Unlike all previously measured metabolic and transport parameters, the dependence of the accumulation ratio on suspension density is not monotonic but shows a pronounced maximum in the range of 4-8 mg dry wt/ml, depending on yeast species and on cultivation conditions. In Rhodotorula gracilis and in Lodderomyces elongisporus it is not due to CO2 but is semiquantitatively related to the proton motive force across the plasma membrane as well as to the intracellular ATP content. It is observed both in oxygen and in argon, over a wide range of pH values and of temperatures, but it is suppressed by metabolic inhibitors. It is expressed only in a range of transported solute concentrations between about 0.1 and 10 mM. PMID- 3332978 TI - [Adhesive strength of Maryland bridges]. PMID- 3332979 TI - [Movement of prefabricated profiled sliding attachments]. PMID- 3332980 TI - [The Cerasand endosseous implant]. PMID- 3332981 TI - [Endosseous screw-implants in aluminium ceramic (crystalline bone screw and Cerasand)]. PMID- 3332983 TI - [Utilization of Frialite implants (Tubingen type). Indications and long-term results]. PMID- 3332982 TI - [The A12O3 Frialite dental implant]. PMID- 3332985 TI - [The Denar Steri-Oss implant system]. PMID- 3332984 TI - [Biolox aluminium ceramic implants]. PMID- 3332986 TI - [Prosthesis on implants]. PMID- 3332987 TI - [Round table on implantology in 1987]. PMID- 3332988 TI - The subunits of succinyl-coenzyme A synthetase--function and assembly. AB - Succinyl-CoA synthetase is made up of two kinds of subunits, designated alpha and beta. The enzyme from Escherichia coli is an alpha 2 beta 2 tetramer (mol. mass. 142 kDa), whereas the mammalian mitochondrial species is an alpha beta dimer. By means of active enzyme centrifugation, we have shown that the active form of the bacterial enzyme is the tetramer even at very low assay concentrations, while the pig heart enzyme is a non-associating dimer over a wide concentration range. The E. coli enzyme shows distinct half-of-the-sites reactivity with respect to the phosphorylation of a histidine residue in the alpha-subunit that represents a step in catalysis. Many lines of evidence (hybrid enzyme formation, oxygen exchange kinetics, 31P-n.m.r. studies) suggest that co-operative interactions between alternatingly functional active sites on the two halves of the E. coli enzyme contribute to its catalytic efficacy. In further refining this model for catalysis, we have shown that the monothiophosphorylated E. coli enzyme does not catalyse exchange of 18O from the beta, gamma-bridge to the beta-non-bridge position of ATP, indicating that the enzyme does not undergo even transient bis phosphorylation. As a first step in studying the in vivo synthesis and assembly of the enzyme in the mammalian mitochondrial matrix, we have cloned and sequenced a 900 bp cDNA fragment that encodes most of the alpha subunit of rat liver succinyl-CoA synthetase. The derived amino acid sequence shows an impressive degree of homology to that of the alpha subunit of the enzyme from E. coli. We have shown that the alpha subunit in rat liver is a discrete nuclear gene product, complete with cleavable signal sequence to specify mitochondrial targetting. PMID- 3332989 TI - The role of the citric acid cycle in fungal organic acid fermentations. AB - Filamentous fungi are well known for their potential to accumulate organic acids in the medium when supplied with large amounts of sugar. Commercial applications of this are the production of citric and itaconic acids. The present review attempts to present the current state of knowledge on the biochemical basis of organic acid accumulation by filamentous fungi (citric, itaconic, fumaric and oxalic acids), particularly with respect to the role of citric acid cycle reactions. The explanations offered are based on recent advances in understanding the compartmentation of the fungal cell, and regulation of some key enzymes. The general conclusion is that fungi accumulate organic acids by mechanisms which avoid the channeling of substrates into the citric acid cycle under conditions of strongly active glycolysis. PMID- 3332990 TI - Hormonal regulation of fluxes through pyruvate dehydrogenase and the citric acid cycle in mammalian tissues. AB - Three key dehydrogenases in the mitochondria of higher animals have been found to be activated by Ca2+ ions; these are pyruvate dehydrogenase and two enzymes in the citric acid cycle, NAD-isocitrate dehydrogenase and oxoglutarate dehydrogenase. Activation can also be demonstrated within permeabilized and intact mitochondria. Evidence is summarized that when hormones and other extracellular stimuli increase the cytoplasmic concentration of Ca2+, then this results in an increase in the intramitochondrial concentration of Ca2+. In this way, rates of pyruvate oxidation and citric acid cycle flux are increased, and hence there is an increase in NADH supply for the respiratory chain under conditions where there is an enhanced demand for ATP. In contrast, the activation of pyruvate dehydrogenase which is observed in adipose and other tissues exposed to insulin is brought about by a Ca2+-independent mechanism. PMID- 3332991 TI - The role of the citric acid cycle in cells of the immune system and its importance in sepsis, trauma and burns. AB - Many aspects of the cell biology of lymphocytes and macrophages have been studied extensively over many years. Our recent work on these cells has investigated the fuels utilized, the metabolism carried out and the importance of this metabolism for the specific function of these cells in the immune system. The quantitatively important role of glutamine and the observation that both glutamine and glucose are only partially oxidized by both types of cell have been established. This work has led to a new hypothesis to explain the high rates of partial oxidation of both fuels in lymphocytes and macrophages, and in other cells such as enterocytes, colonocytes and also in neoplastic cells. In addition, the high rate of glutamine utilization and its importance in such cells has raised the question as to the source of this glutamine in the body: the evidence suggests that this is muscle. The metabolic relationship between the glutamine-producing tissue and the cells of the immune system provides an explanation for some well-established changes in metabolism during the condition of surgery, trauma, sepsis and burns. Knowledge of the metabolism of glucose, glutamine, pyruvate and long-chain fatty acids by these cells raises some intriguing questions concerning the role and function of the citric acid cycle in these and other similar cells, including tumour cells. PMID- 3332992 TI - Enzyme-enzyme interactions as modulators of the metabolic flux through the citric acid cycle. AB - A general analysis of the regulation of the citric acid cycle is hampered by the intimate interplay believed to exist between the various surrounding pathways. Two main regulatory mechanisms are thought to determine the flux through the cycle: (1) regulation of individual cycle enzymes, and (2) reversible complex formation between various enzymes of the cycle and related pathways. The latter mechanism allows a cell to maintain a high flux of substrates with a moderate number of intermediates, and offers a means of metabolite channeling. We were able to demonstrate specific interactions between several vertebrate cycle enzymes in conditions of reduced water concentration, i.e. by using immobilized enzyme systems. From affinity chromatographic experiments, we have shown that the enzymes of the citric acid cycle and the aspartate-malate shuttle are organized as one huge multi-enzyme complex, and a stoichiometric arrangement of fumarase/malate dehydrogenase/citrate synthase/aspartate aminotransferase has been postulated. Affinity electrophoresis was used as a new experimental device by which the enzyme-enzyme interactions could be directly visualized. PMID- 3332993 TI - Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli. AB - The glyoxylate bypass and citric acid cycle operate concurrently in Escherichia coli when acetate is the sole source of carbon and energy to sustain aerobic growth. The overall carbon balance allows fluxes through the central metabolic pathways (CMPs) to be computed on the assumption that these metabolic pathways are known. Acetate is fluxed via the CMPs to the precursors required for synthesis of new biomass and also to generate the reducing power and ATP required to convert these precursors to biomass. Under these circumstances, a junction is created at isocitrate where isocitrate lyase (ICL) and isocitrate dehydrogenase (ICDH) compete for their common substrate. In general, flux through ICL generates the precursors used for biosynthesis while the larger part of the flux (95%) through ICDH is dedicated to the supply of reducing power and ATP. The system sustains a large intracellular pool of isocitrate to accommodate the rather low affinity of ICL for this substrate. Excessive flux of isocitrate through ICDH is prevented by regulation of ICDH activity: reversible inactivation of ICDH is achieved by a bifunctional kinase/phosphatase, as the phosphorylated form of ICDH has no activity. The kinase/phosphatase responds to two classes of effectors- intermediates of the CMPs generated by flux through ICL and the lower energy forms of ATP and NADPH (ADP, AMP and NADP+) generated when these intermediates are used for biosynthesis. The effect is to adjust flux through ICDH so that the rate of supply of NADPH and ATP is equal to the demands of biosynthesis. Biosynthetic fluxes are limited by the rate of supply of precursors which depends on flux through ICL. Growth rate is most likely limited by the primary flux of acetate to acetyl-CoA or flux through ICL. In the steady state, the flux through ICDH is regulated to be twice the throughput of ICL. The evolution of this complex pattern of control may have depended on alternatives to the citric acid for energy generation. PMID- 3332994 TI - Organizational aspects of the citric acid cycle. AB - The enzymes of the citric acid cycle show at least two levels of organization within the mitochondrial matrix. Six of the possible eight sequential enzymes show specific interactions in vitro. Further, the enzymes bind specifically to the matrix surface of the inner membrane. A slightly damaged mitochondrial particle has been isolated which contains bound, but exposed, Krebs citric acid cycle enzymes. This particle (a metabolon) shows a kinetic advantage for two coupled systems, fumarate oxidation and malate conversion to citrate, over a solubilized system. N.m.r. experiments indicate that many components of the matrix are in a bound state. PMID- 3332995 TI - Compensatory regulation in metabolic pathways--responses to increases and decreases in citrate synthase levels. AB - The level of citrate synthase was varied in Escherichia coli by recombinant DNA methods to elucidate regulatory interactions between the individual steps of the citric acid cycle. The effects of overproduction and underproduction of citrate synthase were assessed by measuring metabolite levels, rates of carbon flow, the phosphorylation state of isocitrate dehydrogenase, and the growth rate of the culture. This analysis revealed that the levels of citrate synthase and isocitrate dehydrogenase activity are co-ordinated for efficient growth on acetate. When citrate synthase was overproduced the isocitrate dehydrogenase reaction became rate limiting and prevented large increases in the flux through the citric acid cycle. Furthermore, changes in the level of citrate synthase were found to modulate the phosphorylation state of isocitrate dehydrogenase which regulates the distribution of carbon flow between the citric acid cycle and the glycoxylate shunt. These adjustments allowed the organism to maintain a relatively constant metabolic state despite changes in the level of a central metabolic enzyme. The interplay between citrate synthase and isocitrate dehydrogenase illustrates how living systems can compensate for variations in their internal environment. PMID- 3332996 TI - Evolutionary roots of the citric acid cycle in prokaryotes. AB - Advances in biochemistry, microbiology, and molecular biology suggest new approaches for exploring the early evolution of bioenergetic systems. These approaches, still in their infancy, are necessarily directed to detection of 'molecular fossils' in diverse extant prokaryotes. Since the Earth was devoid of atmospheric oxygen during early cellular evolution, it is likely that 'precursor fragments' of the classical citric acid cycle are to be found in contemporary anaerobic bacteria. Accumulating evidence indicates that such fragments originally served biosynthetic roles of one kind or another, before they were recruited for assembly of the energy-yielding aerobic cycle. The extraordinary versatility of citric acid cycle intermediates and reactions for multiple uses raises the possibility that origination of the aerobic cycle, viewed as an evolutionary event, occurred more than once. PMID- 3332998 TI - Molecular genetic aspects of the citric acid cycle of Escherichia coli. AB - The genes encoding all of the citric acid cycle enzymes of Escherichia coli have been cloned and much has been learned about the structure, function and expression of these enzymes from the nucleotide sequences, the mRNA transcripts and site-directed mutagenesis of the corresponding genes. Special features of the expression of the aerobic cycle, and its anaerobic transformation into a branched pathway in a facultative anaerobe, are considered. Aspects of the structure function relationships of succinate dehydrogenase, succinyl-CoA synthetase, fumarase and related enzymes, and the 2-oxo acid dehydrogenase complexes are reviewed. PMID- 3332997 TI - Patterns of diversity of citric acid cycle enzymes. AB - The citric acid cycle performs a dual role in cell metabolism, acting as a source of both 'energy' and biosynthetic starting materials. The widespread occurrence of the cycle throughout Nature is an excellent example of the unity of biochemistry, but closer examination reveals that there is considerable diversity in the citric acid cycle of different organisms with respect to metabolic role, molecular enzymology and mode of regulation. Two enzymes of the cycle--citrate synthase and succinate thiokinase--have been found to exhibit particularly striking patterns of diversity in structure and catalytic and regulatory function. Some of these patterns show a correlation with the taxonomic groupings of the organisms and with their physiological characteristics. Comparative enzyme studies have a contribution to make to an ultimate understanding of the cycle and its cellular operation, and there are substantial benefits to be gained from interactive studies on both prokaryotic and eukaryotic systems. PMID- 3332999 TI - 2-Oxo acid dehydrogenase multi-enzyme complexes: in the beginning and halfway there. AB - The lipoate acyltransferase components of the pyruvate and 2-oxoglutarate dehydrogenase complexes are highly segmented proteins, forming the structural and mechanistic cores of the complexes. Various functional domains can be isolated by controlled proteolysis, the cleavage sites occurring in conformationally flexible segments of polypeptide chain with unusual sequences. The complexes exhibit novel properties of active-site coupling, which stem from their unusual quaternary structure and the polypeptide chain flexibility that enables protein domains to move with respect to the three contributing active sites during catalysis. In vitro mutagenesis, high resolution n.m.r. spectroscopy and the methods of protein engineering are providing important insights into the mechanics of these processes, with more general implications for the design principles of macromolecular assemblies. PMID- 3333000 TI - Structural basis for regulation in gram-negative bacterial citrate synthases. AB - The citrate synthases of Gram-negative bacteria, unlike those of eukaryotes, are inhibited allosterically by NADH, but the two kinds of citrate synthase are about 30% homologous in amino acid sequence--the two Gram-negative citrate synthase sequences so far determined, from Escherichia coli and Acinetobacter anitratum, are about 70% identical. A model for the NADH-sensitive E. coli citrate synthase has been constructed using sequence homology and the known structure of the pig heart enzyme. The most reactive cysteine in the E. coli enzyme, which probably marks the NADH binding site, has now been identified as Cys-206. The model places this residue far from the active site. An E. coli citrate synthase mutant, from which a stretch of 24 amino acids has been deleted near the active site, still binds NADH normally. Two active site missense mutants of this enzyme, generated by oligonucleotide-directed mutagenesis, have lower affinities for one substrate, oxaloacetate, but also are much less sensitive to 2-oxoglutarate, an oxaloacetate analogue hitherto believed to be an allosteric inhibitor. These results confirm that NADH binds to a truly allosteric site in E. coli citrate synthase, the features of which are still to be defined; while 2-oxoglutarate is really an active-site directed inhibitor, although it may still play a regulatory role in vivo. PMID- 3333001 TI - Regulation of the enzymes at the branchpoint between the citric acid cycle and the glyoxylate bypass in Escherichia coli. AB - During growth of Escherichia coli on acetate, the glyoxylate bypass supplies the precursors needed for biosynthesis. The glyoxylate bypass enzyme isocitrate lyase competes with the citric acid cycle enzyme isocitrate dehydrogenase for the available isocitrate. We have studied the control of metabolic flux at this branchpoint by examining the regulatory properties of the enzymes concerned. Isocitrate dehydrogenase is controlled by reversible phosphorylation catalysed by a bifunctional kinase/phosphatase whose activities are regulated by isocitrate, biosynthetic precursors and adenine nucleotides. The flux through isocitrate lyase is mainly controlled by the intracellular concentration of isocitrate. The phosphorylation system responds to the availability of energy and precursors and maintains isocitrate at a concentration high enough to sustain the flux through the glyoxylate bypass necessary for biosynthesis. PMID- 3333003 TI - Popliteal aneurysm: a celebration of the bicentennial of John Hunter's operation. AB - Analysis of the original documents on Hunter's operation revealed that Hunter himself never realized the theoretical implications of his operation, particularly that collateral circulation could develop following ligation of the main arterial trunk of a limb. This operation, however, marks a monumental step in the history of vascular surgery. Even though supplanted only one century later by Matas' obliterating endoaneurysmorraphy, this technique became the first efficient means of managing popliteal aneurysms, the prognosis of which had been absolutely disastrous until that time, leading to either amputation or death in most cases. PMID- 3333002 TI - Detection of stenoses in the internal carotid artery by waveform analysis of continuous wave ultrasound signals (II). AB - Analysis of the morphological aspects of continuous-wave Doppler examination is a reliable means of detecting carotid stenosis involving 50% or more of the diameter of the arterial lumen. This study was undertaken to evaluate the indexes likely to increase the diagnostic accuracy of this noninvasive investigation method. The indexes studied were the variations of the maximal frequency and the systolic peak frequencies, measured proximal to and at the level of stenosis, and the ratio of the systolic peak frequency measured in the internal carotid artery and in the common carotid artery. After obtaining data on an experimental model, the study was conducted in healthy volunteers (n = 24) and in patients with carotid atherosclerotic disease (n = 23). The experimental study confirmed that stenosis greater than 50% leads to a reduction of blood flow and that there is a mathematical relationship between the frequency measured proximal to and at the level of the stenosis and the degree of stenosis. Clinical data showed that there was a significant decrease in the frequency of the systolic peak in elderly "healthy" subjects as compared with younger subjects. However there was no difference between patients with and without stenosis. The index was 0.8 in young subjects, 1.3 in healthy elderly subjects, and greater than 1.3 in subjects who had a stenosis. There was no statistically significant difference between these two last groups. At the threshold value of 2.3, the sensitivity of the FI index was 22% and the specificity was 94% in the detection of carotid artery stenosis. In the assessment of the tight stenosis, sensitivity was 44%. PMID- 3333004 TI - Intracaval and intracardiac leiomyomatosis of uterine origin. AB - Intracaval leiomyomatosis of uterine origin is a rare disease. Extension to the right heart is exceptional. Based on the review of 11 cases reported in the literature and the case presented herein, which was treated successfully, the diagnostic and therapeutic problems are discussed. Diagnosis should be suggested when a female patient operated on previously for myofibroma of the uterus by hysterectomy, presents with a picture of cardiac myxoma. Diagnosis can be confirmed by iliocavogram and computerized tomography of the abdomen. Excision calls for a cardiac procedure under extracorporeal circulation and caval exploration which may be performed either simultaneously or as a two stage procedure. PMID- 3333005 TI - Gunshot pellet embolus to the middle cerebral artery. AB - A 24-year-old man sustained a gunshot wound to the upper right hemithorax and neck, with injury to the subclavian and carotid arteries. A cerebral artery pellet embolus resulted in contralateral hemiplegia. The injured vessels were repaired, but the middle cerebral artery pellet was left undisturbed. Neurologic improvement occurred. Fifteen cases of foreign body embolus to cerebral vessels are reviewed and the management of this unusual injury is discussed. PMID- 3333006 TI - The first successful resection of an aneurysm of the abdominal aorta followed by re-establishment of continuity using a preserved human arterial graft. PMID- 3333007 TI - Geza de Takats 1892-1985. PMID- 3333008 TI - Detection of stenoses in the internal carotid artery by waveform analysis of continuous wave ultrasound signals (I). AB - In this prospective study, the reliability of the morphologic analysis of the continuous Doppler signal was evaluated. Three parameters were considered: the maximum systolic frequency (max A), a resistance parameter (RP) and the degree of spectral broadening (SB). The apparatus used allowed us to construct a color arterial image. Seventy-four subjects were included in this study: 17 volunteers investigated by ultrasound only, and 57 patients investigated by ultrasound and arteriography. Anatomic correlation was obtained in 31 operated cases. The threshold values, as determined in the volunteers, were as follows: 3.5 kHz for max A, 0.86 for RP and 58% for SB. Sensitivity was 94% when max A, SB and cartography were combined to detect tight stenoses. The sensitivity for each of the parameters alone was much weaker (61% for max A and 33% for RP). For all carotid lesions, the sensitivity of detection when all parameters were combined was 68%. Specificity was 77%. The study of the carotid bifurcation by the continuous Doppler effect allowed us to identify tight stenosis with reliability. On the other hand, it was impossible to distinguish between normal arteries and moderate stenosis, or between tight stenosis and complete occlusion. PMID- 3333009 TI - The carotid web: a developmental anomaly of the brachiocephalic system. AB - A case of a congenital carotid web is reported. This lesion is believed to be a very rare anomaly of carotid development. The embryologic development of the brachiocephalic arteries is discussed. Anomalies of the brachiocephalic arteries including anomalies of origin from the aortic arch, atresia, and persistent communications between the carotid and vertebral system are reviewed. PMID- 3333011 TI - Blunt traumatic dissection of the internal carotid artery treated by balloon occlusion. AB - An extensive traumatic intimal dissection of the internal carotid artery was successfully managed by permanent occlusion of the vessel with percutaneously placed, inflatable balloons in a young patient who had suffered transient ischemic neurological attacks despite anticoagulation. This technique has not been previously reported for treatment of dissection. Review of 34 published reports of symptomatic intimal dissection associated with non-penetrating trauma to the head and neck revealed that most did not have a direct injury to the carotid region and that development of symptoms was often delayed. Only 50% of these patients had onset of neurological symptoms within six hours of the episode of trauma, while 33% remained asymptomatic for more than one week before complications occurred. In 15 patients who were treated surgically, only nine (60%) achieved full recovery. Operative repair was considered unduly hazardous in our patient because of extension of the spiral dissection to the base of the skull. Successful use of percutaneous balloon occlusion of the carotid in this patient suggests that this technique should be considered a worthy alternative for management of selected cases. PMID- 3333010 TI - Combined hepatic and gastric artery aneurysms: a case report and review of the literature. AB - A patient is presented who was successfully managed with metasynchronous rupture of a hepatic and a left gastric artery aneurysm. The subject of visceral artery, hepatic artery, and gastric artery aneurysms is reviewed. The role and limitations of modern interventional radiologic procedures in treating this entity is illustrated. PMID- 3333012 TI - Basic data concerning associated coronary disease in peripheral vascular patients. PMID- 3333013 TI - Mitochondrial transport of K+ and Mg2+. PMID- 3333014 TI - Structure, function and organization of the Photosystem I reaction center complex. PMID- 3333015 TI - Theoretical analysis of double-titration experiments. PMID- 3333016 TI - Hypothesis. The molecular 'double-pivot' mechanism for water oxidation. PMID- 3333017 TI - Effect of calcium and stanozolol on calcitonin secretion in patients with femoral neck fracture. AB - The role of calcitonin in the aetiology of postmenopausal osteoporosis remains uncertain. Oestrogen, an established therapy for postmenopausal osteoporosis, has been shown to enhance calcitonin secretion. In order to assess whether two other osteoporotic drug treatments, oral calcium and stanozolol (an anabolic steroid), may also affect calcitonin secretion, 20 elderly women with femoral neck fracture were randomly selected to receive either 880 mg calcium or 5 mg stanozolol daily for 12 weeks. Basal calcitonin and serum calcium were not altered significantly by either treatment. The calcitonin response to a 10 min infusion of calcium was enhanced following treatment with oral calcium but not stanozolol. This suggests one possible mechanism of action whereby calcium may exert its antiresorptive effect on bone and supports the use of oral calcium in the treatment of postmenopausal osteoporosis. PMID- 3333018 TI - Long-term effect of nandrolone decanoate, 1 alpha-hydroxyvitamin D3 or intermittent calcium infusion therapy on bone mineral content, bone remodeling and fracture rate in symptomatic osteoporosis: a double-blind controlled study. AB - A double-blind controlled study was performed in 60 patients with symptomatic osteoporosis with at least one vertebral crush fracture, comparing the effect of nandrolone decanoate, 1 alpha-hydroxyvitamin D3 and intermittent calcium infusions. Thirty-four out of 60 patients completed the 2 year observation period. Nandrolone decanoate statistically significantly increased the bone mineral content at the radius, reduced the endosteal bone loss at the metacarpals and statistically significantly reduced urinary calcium and hydroxyproline excretion. Calcium infusions and 1 alpha-hydroxyvitamin D3 inhibited further loss of bone mineral content, but endosteal bone loss continued. In the second year fracture rate was reduced in the nandrolone decanoate groups compared to the two other groups. We conclude that nandrolone decanoate is an active drug for increasing bone mineral content and reducing endosteal bone loss, while 1 alpha hydroxyvitamin D3 and calcium infusions only stop further bone mineral loss at the radius but do not inhibit endosteal bone loss as measured at the metacarpals and that single photon absorptiometry and radiography are complementary in interpreting cortical bone mineral changes. PMID- 3333019 TI - The mechanostat: a proposed pathogenic mechanism of osteoporoses and the bone mass effects of mechanical and nonmechanical agents. PMID- 3333020 TI - Effectiveness of drug information centers. AB - Drug information centers (DICs) have existed for more than 20 years in the U.S., with the number growing over this period to approximately 120 centers. Although future growth in the number of centers will be limited, the present activities will become more refined and productive. The present activities of drug information centers can be classified into three general areas: service, education, and research. The scope of the services provided often depends on location and affiliations. Likewise, these same factors may influence involvement in education and research activities. The effectiveness of centers is measured most often in terms of service productivity and perceived value by users. The methods and results of such evaluations are reviewed with discussion of the need to develop more definitive standards of practice. PMID- 3333021 TI - The synergism of Health Information Science/Health Informatics. AB - The purpose of this paper is threefold: to review the status of Health Information Science (Health Informatics) as reported in the literature; to suggest a taxonomy to integrate the many varied concepts being discussed under the rubric of Health Information Science; and to propose a framework into which research can be classified and potential research hypotheses generated. It is suggested that such a framework is needed if generalizations are to be made to the end that the knowledge produced from research efforts may be cumulative with that from other studies. A framework for research is needed if the field is to become an established academic discipline; whether or not it takes on the mantel of a "science" is another matter. PMID- 3333022 TI - A review of computer ECG analysis: time to evaluate and standardize. AB - The use of computers for the interpretation of the resting electrocardiogram (ECG) is critically reviewed. After a short description of the motives for the application of computers in this field, the processes that are sequentially executed in an ECG data processing system are critically analyzed, i.e., the acquisition and transmission of signals; the wave recognition and measurement phase; the parameter extraction, rhythm analysis, and classification phases; and, finally, the reporting of results as well as serial comparison. Emphasis is given on the evaluation and standardization of measurement and interpretation results of various ECG computer programs, based on the experience of the author as project leader of the International Cooperative Project "Common Standards for Quantitative Electrocardiography" (CSE). An extensive list of references is provided. PMID- 3333023 TI - Control of the bioavailability of a topical steroid; comparison of desonide creams 0.05% and 0.1% by vasoconstrictor studies and clinical trials. PMID- 3333024 TI - Cyclic nucleotide metabolism in atopic dermatitis. PMID- 3333025 TI - Culture-grafted leg ulcers. PMID- 3333028 TI - [Highly technology-oriented medicine and oral surgery]. PMID- 3333027 TI - [Clinical evaluation of the use of local haemostatic Surgicel for extraction cavity. Haemostatic effect and healing process of extraction cavity]. PMID- 3333026 TI - Fibreoptic endoscopy of the equine upper respiratory tract: a commentary on progress. PMID- 3333029 TI - [Studies of experimental resin sealant containing functional monomers]. PMID- 3333030 TI - [Electron microscopic observation of sharp and dull sickle scalers]. PMID- 3333031 TI - [The effect of total etching system on dentin and pulp]. PMID- 3333032 TI - [A case of odontogenic fibroma found during orthodontic treatment]. PMID- 3333034 TI - New aspects in the free-radical chemistry of pyrimidine nucleobases. AB - i) It has been known for some time that OH radicals and H atoms react with the pyrimidines by adding to the C(5)-C(6) double bond, but only the u.v.-spectra of the sum of these radicals have been reported so far. It will be shown how to arrive at the individual spectra of the C(5) and the C(6) adduct radicals. ii) alpha-Hydroxyalkyl radicals are known to inactivate biologically active DNA. In contrast to the electrophilic radicals H and OH they are nucleophilic and the hydroxymethyl radicals add exclusively at the C(6) position of 1,3-dimethyluracil (k approximately 10(4) dm3 mol-1 s-1). In the corresponding thymine derivative this reaction also occurs, but one third of the hydroxymethyl radicals abstract an H-atom from the C(5)-methyl group thereby forming an allylic radical. In the course of these reactions pyrimidines with an exocyclic double bond are formed. These products react much more rapidly with hydroxymethyl radicals than the starting material leading to highly hydroxymethylated material at very low doses. iii) The direct effect of ionizing radiation which would produce a pyrimidine base radical cation can be mimicked by reacting the pyrimidine with SO4-, a very good electron acceptor. In water, the radical cation of 1,3-dimethyluracil is rapidly (t1/2 less than 2 microseconds) converted into the C(5) OH adduct radical. In the presence of peroxodisulphate a chain reaction sets in which leads to the cis-glycol. PMID- 3333033 TI - Free radical induced degradation of 1,2-dibromoethane. Generation of free Br. atoms. AB - Free Br. atoms have been found to be generated upon eaq- and .OH radical induced degradation of 1,2-dibromoethane in aqueous solution. The relevant process is beta-bromine cleavage from CH2BrCH2 and CH2BrCHBr radicals, respectively. An absolute rate constant of k = 2.8 x 10(6) s-1 has been determined for the reaction CH2BrCH2----Br. + CH2 = CH2, while an estimate of k approximately 10(6) s-1 can be given for CH2BrCHBr----Br. + CH2 = CHBr. The Br. atoms have been identified through their reaction with Br- to Br2-. (k = 7.7 x 10(9) mol-1dm3s-1) and their reaction with 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonate) (k = 6.8 x 10(9) mol-1dm3s-1). Ethylene and vinyl bromide have been identified via GC. The results substantiate earlier findings that free radical induced mechanisms can serve as informative probe for metabolic processes. PMID- 3333035 TI - Problems associated with distinguishing between singlet oxygen and electron transfer photooxygenation reactions. AB - In the introduction a review is given of the various methods available for probing the mechanism of photooxygenation reactions. To illustrate the methodology, some new results on the photooxygenation of alpha-ketocarboxylic acids and esters is given in which it is shown that these compounds sensitise singlet oxygen formation but are relatively unreactive to this oxidising species. Alternative mechanistic schemes are proposed. PMID- 3333036 TI - [The degree of the staining test of various composite resins. Part 3. Differences in the measurements of leakage due to various bonding agents]. PMID- 3333037 TI - [The bond strength of commercial visible light cured composites (II)]. PMID- 3333038 TI - [The mechanical properties of pure titanium for dental casting]. PMID- 3333039 TI - [Allergy to local anesthetics]. PMID- 3333040 TI - [Hydroxyapatite augmentation of the mandibular alveolar ridge]. PMID- 3333041 TI - [A clinical study of artificial tooth roots using composite apatite ceramic implants]. PMID- 3333042 TI - [A medium for reduction of chlamydospore forming time in Candida albicans]. PMID- 3333043 TI - Adhesive ability of a dental adhesive resin (4-META/MMA-TBB) to As-polished, HNO3 treated, and oxidized surfaces of the Ni-Cr alloy. PMID- 3333044 TI - [A case analysis of an edentulous patient; occlusal sound analysing in complete denture retention and stability]. PMID- 3333045 TI - [Removable partial dentures: Part 5. Plaque build-up and pockets of abutment teeth]. PMID- 3333046 TI - [Marked shrinkage of gingiva after initial preparation: a case report]. PMID- 3333047 TI - [Two cases of congenital partial anodontia]. PMID- 3333048 TI - [Observation of the pronunciation in anterior teeth treatment]. PMID- 3333049 TI - [Clinical evaluation of a tissue conditioning material (TISSUE CONDITIONER)]. PMID- 3333050 TI - [Studies on new dental investment containing AIPO4]. PMID- 3333051 TI - [Statistical error analysis in plaster working models. I. Replacement error of dental plaster dies]. PMID- 3333052 TI - [Practical performance of various prepared abutment forms]. PMID- 3333053 TI - [Statistical investigations of preparation gradients on the dental plaster dies in polyclinics]. PMID- 3333054 TI - [The influence of palatal plate thickness on functional mandibular movement]. PMID- 3333055 TI - [A psychological approach to bruxism--application of muscle relaxation training and autogenic training]. PMID- 3333056 TI - Vector introduction and malaria infection on Guam. AB - The Mariana Islands lie well within the vast "malaria-free" region of the central and south Pacific Ocean. However, Anopheles indefinitus was discovered on Guam in 1948, and an additional four species of Anopheles were collected on the island during 1970-75. Early malaria cases on Guam were diagnosed as relapsing infections with the disease having been contracted in other areas. Small outbreaks of malaria were recorded on Guam in 1966 and 1969, and autochthonous cases were indicated in both. Since vector capability for malaria does exist on Guam, quarantine procedures at the air and seaports combined with public health disease surveillance and an integrated anopheline control program are recommended for the island. PMID- 3333057 TI - Control of mosquito nuisance in Britain. AB - The situation regarding mosquito nuisance and control in Britain is presented together with data resulting from a questionnaire circulated to Local Authorities throughout England, Scotland, Wales and Northern Ireland. Details of several recent control programs are given. PMID- 3333058 TI - Some entomological observations on malaria transmission in a remote village in northwestern Thailand. AB - Anopheline mosquitoes and their relation to malaria transmission were studied during the months of March, May and July in the Karen village of Mae Tha Waw located in the northwestern mountains of Tak Province. Thirteen species were captured on human bait during 80 man-nights of collecting. Four additional species were collected during routine larval surveys. Anopheles minimus and An. maculatus comprised 92.5% of the specimens captured biting man. Anopheles minimus and An. nivipes were implicated as vectors based on the detection of sporozoite infections using enzyme-linked immunosorbent assays for Plasmodium falciparum and P. vivax. Anopheles dirus was rarely encountered and probably played little part in transmission in Mae Tha Waw during the period of study. Information is provided on nightly biting activity, incidence of disease, infectivity and larval bionomics. PMID- 3333059 TI - A method of computing the effectiveness of an insecticide. 1925. PMID- 3333060 TI - Newly incriminated anopheline vectors of human malaria parasites in Junin Department, Peru. AB - Sporozoite data from salivary gland dissections are presented that clearly incriminate Anopheles trinkae, An. pseudopunctipennis, An. sp. near fluminensis, An. oswaldoi, An. nuneztovari and An. rangeli as vectors of malaria parasites in the Rio Ene Valley, a hyperendemic malarious area in Junin Department, eastern Peru. Anopheles trinkae is considered the most important vector based on dissections, abundance and man-vector contact. Other notes are presented on the relative abundance, bionomics and previous records of these species in Peru and in the study sites. PMID- 3333061 TI - Sources of funding research for minority investigators. PMID- 3333062 TI - Application of expanded polytetrafluoroethylene (ePTFE) tubing to the study of human wound healing. AB - Wounds are a part of daily life. They range from minor nicks and cuts to the incisions of major surgery. In the sequence of evolution the process of healing arose long before modern science. The events which we are beginning to unravel have occurred routinely for a very long time despite our lack of understanding. We have learned how to nurture healing, but how to modify healing in a positive sense is only an approaching reality. Standardized tests of human healing are a necessary part of future research in wound healing. In the Wound Healing Laboratory we have used tubes of expanded polytetrafluoroethylene (ePTFE) as a tissue-sampling device in small, experimental, needle-stick wounds. Ingrowth into ePTFE is influenced by surface and structural characteristics. These are held constant, and "normal" values can be established and used as a base with which to study effects of various clinical states on healing in humans. PMID- 3333063 TI - Tissue response to biodegradable injectable microcapsules. AB - Biodegradable microcapsules have been shown to be capable of delivering a sustained release of various medicinal agents. We have observed an initial minimal, sharply localized, acute inflammatory response to intramuscularly injected microcapsules produced from various polymers. Evaluation of later time points has shown a diminishing macrophage, foreign body giant cell, and connective tissue response along with actual microcapsule degradation. No fibrous capsule formation was seen. Complete resolution of the tissue reaction can be expected, with the time frame depending upon the polymer utilized. Published experimental results report similar minor tissue responses to a variety of injected biodegradable microcapsules. PMID- 3333064 TI - Strategies for biological testing of biomaterials. AB - Current perspectives on empirical, modeling, and mechanistic methods of medical device safety testing are reviewed. Empirical approaches, such as the U.S. Pharmacopeial biological tests for plastics, evaluate the total system to discover aberrations and abnormalities. Models consist of a single aspect of an integrated approach, whereas mechanistic methods are based on a thorough knowledge of the materials and the organism's biological response. Empirical studies develop data on general hazard potential, such as overt toxicity. Model approaches target the specific application and specific hazard potential. Mechanistic studies identify the cause of toxicity and can produce advances in the biocompatibility of medical devices. PMID- 3333065 TI - Current concepts for assessing blood compatibility: small diameter vascular prostheses. PMID- 3333066 TI - A review of structural and material properties of vascular grafts. AB - A brief review of the textile structures employed in the construction of vascular grafts is followed by a survey of the causes of failure cited in the literature. An attempt is made to determine the structural factors contributing to the failure of vascular grafts, and attention is given to material properties and methods for determining these attributes. Need for further research is emphasized. PMID- 3333067 TI - Antithrombogenic heparin-bound polyurethanes. AB - Many kinds of heparin-bound polyurethanes have been developed. Polyurethanes are a family of elastomers displaying better blood-compatibility than other polymeric materials. It is useful to modify this material by heparinization. Several approaches to heparinization have been devised: 1) a general method of heparinization, applicable to all polymeric materials, 2) a heparinization method specific to polyurethanes, and 3) the design of heparinizable polyurethane derivatives. These three approaches are first explained in detail. Then, the antithrombogenic mechanism of the heparinized polymers is discussed. Finally, the interactions of the heparinized polymers with blood coagulation factors, plasma proteins, and platelets are discussed. PMID- 3333068 TI - Manual performance in the cold: a review of some of the critical factors. PMID- 3333069 TI - Interventional radiology. PMID- 3333070 TI - The Royal Navy and the spread of vaccination. PMID- 3333071 TI - Dementia and trauma. PMID- 3333072 TI - Beyond the right to life--the right to health. PMID- 3333073 TI - Death by hanging. PMID- 3333074 TI - Medical expert testimony in the Jean Harris case. PMID- 3333076 TI - [Interaction of cyclosporin A and rifampicin in a case of kidney transplantation]. PMID- 3333075 TI - Heart damage comparing three strains of mice chronically infected with Trypanosoma cruzi. PMID- 3333077 TI - [Amyloidosis of the central nervous system]. PMID- 3333078 TI - [The Alfred Lanari Medical Research Institute 30 years after its founding]. PMID- 3333079 TI - [Monoclonal antibodies in oncology, a new hope for an unsolved problem]. PMID- 3333080 TI - [History of immunology in Argentina]. PMID- 3333081 TI - [Houssay and clinical research in Argentina]. PMID- 3333082 TI - [The training of a physiologist: B. A. Houssay]. PMID- 3333083 TI - Chemical reaction for aerobic E. coli growth: stoichiometry and thermodynamic. PMID- 3333084 TI - [Fluorine and flora of the oral cavity: relationship to dental caries]. PMID- 3333085 TI - [Prevention and epidemiology of dental caries. Acquisitions and new parameters]. PMID- 3333086 TI - [Epidemiology, etiopathogenesis and prevention of periodontal disease: review, update]. PMID- 3333087 TI - Connubial lymphoma in a middle-aged couple. PMID- 3333088 TI - Erythropoietin--advent of a new treatment. PMID- 3333089 TI - Radiological investigation of the female genital tract. PMID- 3333090 TI - Driver reaction times in car-following situations. PMID- 3333091 TI - [Flap operation--review of the literature]. PMID- 3333092 TI - [Change in the acid-etched enamel surface in the mouth]. PMID- 3333093 TI - [A case of teratoma of the buccal mucosa in an infant]. PMID- 3333094 TI - [Stress analysis of abutment teeth on removal of R.P.D.'s (Part 1). Abutment stress under various retainers]. PMID- 3333095 TI - Effects of analogs of thromboxane A2 and prostacyclin on 45Ca release from neonatal mouse calvaria. PMID- 3333096 TI - [The microcirculation in teeth and periodontium (Part 1). Ultrastructural and tracer studies of blood capillaries in rat molar gingiva]. PMID- 3333097 TI - [Restoration of the "supporting zone" of the mandible in partially dentate mouth (Part 5). Supporting ability of free-end saddle R.P.D.'s]. PMID- 3333098 TI - [Correlation of the diagnostic contribution of ultrasound and radioimmunologic tests in threatened pregnancy in the 1st trimester]. PMID- 3333099 TI - [The effect of solutions used for hypothermia on cells cultured in vitro]. PMID- 3333100 TI - [Bullous diseases and their monitoring at the dermatology clinic]. PMID- 3333101 TI - [Influences of hardness of heavy-body-type silicone impression materials on dimensional accuracy of stone dies]. PMID- 3333102 TI - [Studies on reproducibility of sharp angles to stone models]. PMID- 3333103 TI - [Statistical observation of removable partial dentures. Part 4. Breakage of dentures]. PMID- 3333104 TI - [Effect of fluoride concentration on the remineralization of acid-etched enamel]. PMID- 3333105 TI - [Emphysematous pyelonephritis. Apropos of 2 cases with a review of the literature]. PMID- 3333106 TI - [Preoperative diagnosis of parathyroid adenoma using ultrasonography]. PMID- 3333108 TI - [2 cases of rupture of a rudimentary uterine horn]. PMID- 3333107 TI - [2 cases of cystic dilatation of the common bile duct]. PMID- 3333110 TI - [Valvular replacement in endocarditis of the natural valve. Apropos of 65 cases]. PMID- 3333109 TI - [Unusual osteo-chondrodysplasia: hereditary deforming exostoses. Apropos of a family]. PMID- 3333111 TI - [Morphological aspects of the bile ducts and their therapeutic impact. Apropos of 415 cases 1980-1985]. PMID- 3333112 TI - [Kawasaki syndrome in Tunisia. Apropos of 2 new cases]. PMID- 3333113 TI - [Adenocarcinoma of the appendix. Apropos of 2 cases]. PMID- 3333114 TI - [Fibroplastic endocarditis of the right heart. Apropos of a case and review of the literature]. PMID- 3333115 TI - [Problems posed by celiac disease in Tunisian children]. PMID- 3333116 TI - [The role of ultrasonography in the study of tumors of the salivary glands]. PMID- 3333117 TI - [Surgically treated hydatid cyst of the liver: value of echographic control]. PMID- 3333118 TI - [Should acute diffuse appendicular peritonitis be drained?]. PMID- 3333119 TI - [Histiocytosis X in children. Apropos of 22 cases]. PMID- 3333120 TI - [Diagnosis and treatment of duodenal-pancreatic injuries. Apropos of 26 cases]. PMID- 3333121 TI - [Sigmoid ameboma: apropos of a case]. PMID- 3333122 TI - [Primary malignant lymphoma of bone. Apropos of a case]. PMID- 3333123 TI - [The scimitar syndrome. Apropos of a case with review of the literature]. PMID- 3333124 TI - Increase in growth rates and yields by agitation of Trypanosoma cruzi cultures in liquid medium. PMID- 3333125 TI - Giardiasis. Functional, immunological and histological study of the small bowel. Therapeutic trial with a single dose of tinidazole. AB - Fourteen patients between the ages of 9 months and 5 years with chronic diarrhea and giardiasis were studied. Ten were eutrophic and 4 undernourished. The parasitological diagnosis was based on stool examination, a trophozoite search in duodenal aspiration, mucus adhered to mucosa and parasite identification in the intestinal biopsy material. Functional intestinal absorption studies, IgA determination in intestinal secretions and immunofluorescence studies were made. After the tests, tinidazole in suspension was administered at 60-70 mg/kg in one single oral dose. Patients were clinically re-evaluated and tests were done again after 30 days. The purpose of this paper was to evaluate the changes in the functional morphologic and immunologic studies and the therapeutic efficacy of the drug in a single dose. Nine patients had good clinical results, 2 fair and 3 were not evaluated due to celiac disease. All had negative results on the parasitological tests after treatment. There was no relationship between the number of parasites and the severity of symptoms. There was no significant difference between stool fat and d-xylose at the time of diagnosis and 30 days after the administration of tinidazole. The lactose tolerance test presented a significant difference (p less than 0.05) in the disaccharide absorption after treatment. The secretory IgA revealed significantly lower value (p less than 0.01) with respect to the normal values. The immunofluorescence showed productive IgA cells in all cases. The histologic changes were: mild enteropathy (grade I) in 6 patients; moderate (grade II) in 5; and severe (grade III-IV) in 3. Improvement of the mucosa was seen in 6 patients. PMID- 3333126 TI - [Leiomyoblastoma. Apropos of a case of jejunal localization]. AB - Jejunal leiomyoblastoma was first described in 1960, and since then many reviews were made because its histological particularity, biological behavior, and rarity. Gastric localization is most common, and only 6 jejunal cases were described. A case of a 48 years old man with tumoral mass localized only on a proximal jejunum loop was operated because of intestinal obstruction due to intussusception of a jejunal leiomyoblastoma. Although the presence of some malignant criteria like lymphnodes and peripancreatic tissue metastasis after one year of follow-up, no sign of disease was present. PMID- 3333127 TI - Cholesteryl ester storage disease. Report of a case. AB - Cholesteryl ester storage disease (CESD) is a rare disorder of familial incidence characterized by the accumulation of cholesteryl ester and triglycerides in the liver, intestine and bone marrow. Until now only 21 cases have been reported in the literature. We present a 9 months old girl presenting with increased abdominal girth. She had normal liver function tests and increased cholesterol and triglycerides serum levels. The liver biopsy showed many cholesterol cristals seen as needle shaped cristals under polarized light. This is the youngest patient being diagnosed clinically in the literature. PMID- 3333128 TI - Conformations of hydrophobic polyelectrolytes. AB - Recent studies on the (hypercoiled) compact conformation and the pH-induced conformational transition to the extended coil of the hydrophobic poly(acids or bases), which have been well used in industrial and medical circles, are summarized, especially on the basis of our studies on poly(alpha-alkyl acrylic acids) and maleic acid copolymers with hydrophobic aromatic monomers. The stability of the compact conformation and values of various thermodynamic parameters of the transition of the hydrophobic polyelectrolytes suggest the importance of hydrophobic interaction among the side chains to form the compact conformation. Characterization of various physicochemical methods, including 1H NMR measurements, gives a model of the compact conformation with a more expanded structure than in globular proteins, a free-draining property of the solvent, the conformation fluctuation, etc. Also, the apparent two-state character of each segment in the transition region, a life-time in each state and the cooperative parameter for the compact form formation are discussed. A review of our conformational studies on the hydrophobic-hydrophilic polypeptides is also given. For the anion-induced conformation transition in basic homopoly(alpha-amino acids), hydrophobic characters of the anion and the side chain in the polypeptide are shown to be important, especially in terms of solvation. The difference in the induced conformation by the anion between random and alternating basic copolypeptides is explained by introducing a model which shows the importance of the sequence of hydrophobic and hydrophilic residues in the polypeptide to induce the ordered conformation of the anions. Also, we attempt to explain the difference between the induction of ordered conformation in the basic homo- or copolypeptide in reversed micelles with a large sulfonate (AOT) vs. that in aqueous AOT in terms of the hydrophobic character of the side chains in the polypeptides, AOT and the medium. PMID- 3333129 TI - Interactions of neutral molecules with ionic micelles. AB - The interactions of neutral molecules with ionic micelles are analyzed. The cell and mass action models are presented in order to provide a semi-quantitative description of the solubilization process. Both approaches are discussed from a thermodynamic and kinetic point of view and the different definitions of solute incorporation constants are also discussed and compared. An extensive compilation of standard free energies of transfer from water to micelles is provided and the basis of the employed methods to obtain them is presented. Several aspects of the solubilization process such as its dynamics, the effect of additives, the probe microenvironment and its dependence with the solute mean occupation number are reviewed and critically discussed. The effect of solute incorporation upon the micelle shape and size is also briefly reviewed. PMID- 3333130 TI - Adsorption and adhesion processes in microbial growth at interfaces. AB - By considering bacteria as living colloidal particles it is possible to define, at least in part, the physicochemical and biological factors involved in the adhesion of bacteria to apparently inert surfaces. Adhesion is considered in terms of the attraction and repulsion forces operative as the organism approaches a substratum surface, as well as in terms of the surface free energies of the bacterium, the substratum and the liquid phase. Bacterial adhesion at a surface is preceded by molecular adsorption, a process that may alter the substratum surface properties and may provide a concentrated source of nutrients allowing limited growth of the bacteria at the surface. PMID- 3333131 TI - Adsorption of proteins from solution at the solid-liquid interface. AB - The purpose of this article is to present some general principles and rules for the adsorption of proteins from aqueous solution on solid surfaces, emphasizing conformational and reversibility aspects. Special attention is paid to the relation between structural properties of the protein molecule and its adsorption behavior and to the role of small ions in the overall adsorption process. Thermodynamic analysis reveals that, under many conditions, the adsorption is driven by an entropy increase that is (partly) related to changes in the structure of the protein molecules. PMID- 3333132 TI - Spread monolayers of proteins. AB - The study of spread monolayers of proteins is of interest for understanding the fundamental behavior of proteins as well as the many phenomena resulting from their ubiquitous presence at interfaces in nature. Spread monolayers of proteins is a branch of the developing field of membrane mimetic chemistry. In recent times, it has been somewhat neglected in comparison to other branches (such as bilayers, liposomes and vesicles), despite the unique advantage that the arrangement and packing of molecules in monolayers may be measured and controlled. Methods for spreading proteins and techniques used for their manipulation are outlined. As well as the more traditional methods (such as surface pressure, potential and viscosity), more recent innovations, including removal of monolayers on slides for study by radiotracer techniques, electron diffraction and infrared (IR) spectroscopy, are discussed. Direct optical methods for the study of monolayers in situ are also available (e.g., multiple reflectance spectroscopy, ellipsometry). The use of measurements in the low pressure region to measure molecular weights is discussed. At higher pressures, configurational changes, surface coagulation and desorption are all observed. Experimental and theoretical work on the desorption of proteins from the air/water interface is reviewed. The introduction of multicompartment film balances has proved valuable for the study of reactions occurring in monolayers. This instrumentation has been applied to the study of enzyme reactions at the surface, of direct relevance to reactions where the enzyme is immobilized in the cell membrane. Some applications of monolayer studies are briefly illustrated with reference to biological membranes, foams and emulsions and biomedical problems. PMID- 3333133 TI - Size of bile salt micelles: techniques, problems and results. AB - The current state of the knowledge of the size and the aggregation numbers of micelles formed in solutions of bile salts was evaluated. The experimental techniques considered include static light scattering, sedimentation equilibrium, membrane osmometry, sedimentation velocity and translational diffusion. The theoretical background of each method is briefly discussed, the working equations are summarized and the limitations of each technique are enumerated. Various interaction parameters and their effects on the measured micellar size are discussed. A brief survey of the recent experimental results from the author's laboratory is presented. PMID- 3333134 TI - Micellization and solubilization of phospholipids by surfactants. AB - Phospholipids comprise the major component that defines biological membranes. Yet these amphiphilic molecules exist as liquid crystals when they are dispersed in water. Surfactants which form micelles in aqueous solution are quite useful in solubilizing the phospholipids by converting them into mixed micelles. Phospholipids containing short-chain fatty acids have also been chemically synthesized and these form micelles themselves without added surfactants. Below their cmc, monomers of these synthetic phospholipids can be co-micellized with surfactants. The solubilization of natural phospholipids and the micellization of synthetic phospholipids as well as their co-micellization by surfactants will be discussed. Emphasis will be placed on nonionic surfactants where the formation of micelles and mixed micelles with phospholipids has been well studied. PMID- 3333135 TI - The chain conformations in membranes and micelles. AB - Theory and experiment have recently converged to permit a coherent description of the molecular organization of the hydrocarbon tails within surfactant micelles, monolayers, bilayers and other amphiphilic aggregates. The theory is reviewed here, presented in simple form, and is compared to experiments. It is concluded that molecular organization arises from the interfacial localization of amphiphilic chain molecules whose equilibrium conformations are as random as permitted by packing and intramolecular constraints. PMID- 3333136 TI - Interfacial interactions between proteins and mammalian lipases. AB - The effects of proteins, both endogenous and exogenous, on the activity of lipases against water soluble and water insoluble substrates have been reviewed. The enzymes considered are pancreatic and gastric lipases, and lipoprotein, bile salt-stimulated human milk and pancreatic carboxyl ester lipases. A brief account is given of the function of each enzyme and of the physical properties of the interacting proteins, which include albumins, lysozymes, globulins and immunoglobulins, myoglobin, transferrins, alpha-lactalbumin and melittin. With few exceptions (for example, the effect of colipase on pancreatic lipase), the interaction of proteins with lipases which act at the lipid-water interface of water insoluble substrates results in deactivation of enzymic activity. It seems that the amphiphilic nature of proteins allows them to aggregate at interfaces, thereby altering the nature of the interface and decreasing accessibility of the substrate to the enzyme. This discussion gives consideration to association of the proteins with the enzyme or the interface and to whether the interactions with specific binding sites or interfacial inactivation are responsible for the observations. However, the effect of proteins on lipases acting against water soluble substrates varies from protein to protein. Activation of enzyme-activity occurs if the interacting proteins are able to act as acyl transfer agents and thus introduce another catalytic hydrolysis pathway into the reaction mechanism. Inhibition may be caused by specific interactions between the protein and the enzyme or the substrate. PMID- 3333137 TI - Monopolar surfaces. AB - Following the development of a methodology for determining the apolar components as well as the electron donor and the electron acceptor parameters of the surface tension of polar surfaces, surfaces of a number of quite common materials were found to manifest virtually only electron donor properties and no, or hardly, any electron acceptor properties. Such materials may be called monopolar; they can strongly interact with bipolar materials (e.g., with polar liquids such as water); but one single polar parameter of a monopolar material cannot contribute to its energy of cohesion. Monopolar materials manifesting only electron acceptor properties also may exist, but they do not appear to occur in as great an abundance. Among the electron donor monopolar materials are: polymethylmethacrylate, polyvinylalcohol, polyethyleneglycol, proteins, many polysaccharides, phospholipids, nonionic surfactants, cellulose esters, etc. Strongly monopolar materials of the same sign repel each other when immersed or dissolved in water or other polar liquids. The interfacial tension between strongly monopolar surfaces and water has a negative value. This leads to a tendency for water to penetrate between facing surfaces of a monopolar substance and hence, to repulsion between the molecules or particles of such a monopolar material, when immersed in water, and thus to pronounced solubility or dispersibility. Monopolar repulsion energies can far outweigh Lifshitz-van der Waals attractions as well as electrostatic and "steric" repulsions. In aqueous systems the commonly observed stabilization effects, which usually are ascribed to "steric" stabilization, may in many instances be attributed to monopolar repulsion between nonionic stabilizing molecules. The repulsion between monopolar molecules of the same sign can also lead to phase separation in aqueous solutions (or suspensions), where not only two, but multiple phases are possible. Negative interfacial tensions between monopolar surfactants and the brine phase can be the driving force for the formation of microemulsions; such negative interfacial tensions ultimately decay and stabilize at a value very close to zero. Strongly monopolar macromolecules or particles surrounded by oriented water molecules of hydration can still repel each other, albeit to an attenuated degree. This repulsion was earlier perceived as caused by "hydration pressure". A few of the relevant colloid and surface phenomena are reviewed and re-examined in the light of the influence of surface monopolarity on these phenomena. PMID- 3333138 TI - The role of endomyocardial biopsy in the diagnosis of cardiac disorders in infants and children. AB - Endomyocardial biopsies from 26 children were studied by light and electron microscopy. Follow-up biopsies were obtained in 2 patients. The biopsy showed evidence of myocarditis in 6 patients, including 1 with features of sarcoidosis. Twelve biopsies showed features consistent with dilated cardiomyopathy. Endocardial fibroelastosis was documented in two of these biopsies. In two biopsies striking myocardial hypertrophy with prominent myofibrillar disarray suggested hypertrophic cardiomyopathy. Two biopsies from patients with clinical hypertrophic cardiomyopathy showed ultrastructural evidence of a mitochondrial abnormality. No morphological changes were detected in five biopsies, of which two had carnitine deficiency. A biopsy sampled the overlying myocardium in 1 patient with a cardiac fibroma, and a biopsy of the right ventricle was normal in a patient with Noonan's syndrome and hypertrophic cardiomyopathy limited to the left ventricle. Thus, of 28 biopsies in this series, the morphological changes were diagnostic in 10 (35%) and an additional 13 (46%) biopsies documented an abnormality of the myocardium. Endomyocardial biopsies can be of significant use in the diagnosis of selected cardiac disorders in childhood. PMID- 3333139 TI - Ischemic myocardial necrosis and papillary muscle dysfunction in infants and children. AB - Ischemic myocardial and papillary muscle dysfunction has considerable implication in newborn infants and children with normal or malformed hearts. Papillary muscle dysfunction in adults primarily involves coronary artery occlusion and ischemic necrosis in the left ventricle and papillary muscles. Infants and children rarely develop coronary artery occlusion. Their myocardial dysfunction and injury occurs with nearly equal frequency in both ventricles as a result of underperfusion from a wide range of causes, including severe birth asphyxia, congenital heart disease, and complications of premature delivery. A history of cardiogenic shock, acute congestive heart failure with cyanosis and atrioventricular murmur, or persistent fetal circulation in a newborn without congenital heart disease should alert the pathologist to the possibility of ischemic myocardial necrosis (IMN). Older infants with ventricular hypertrophy, persistent pulmonary hypertension (PPHN), bronchopulmonary dysplasia (BPD), and those with malformed hearts involving severe ventricular hypertension due to outflow obstruction or pulmonary hypertension may have IMN, fibrosis, or dystrophic calcification alone or in combination. Animal models of adult ischemic cardiac injury may not be suitable for study of the newborn. PMID- 3333140 TI - The effects of metabolic diseases on the cardiovascular system. AB - Many metabolic diseases result in pathological changes within the cardiovascular system, often with the most severe effects on the function of the heart and great vessels. Metabolic disorders affecting the heart include disorders of amino acid metabolism, storage diseases, neuromuscular diseases, diseases of metal and pigment metabolism, carnitine deficiency, and connective tissue disorders. Several inborn errors of metabolism may involve the myocardium due to the accumulation of abnormal metabolites in the myocardial cells. In addition, the heart valves and coronary vessels may be involved. If the predominant effect is in the myocardial cell, it will be manifested clinically as a cardiomyopathy. Some disorders, in particular oxalosis, may involve the conduction system as a result of the deposition of oxalate crystals and result in conduction disturbances such as in alkaptonuria, primary oxalosis, and homocystinuria. Myocardial involvement may result in cardiomyopathy of the three functional types: (1) congestive, as in Fabry's disease, (2) hypertrophic, as in glycogen storage disease, type II, or (3) restrictive, as in Gaucher's disease. In the storage disease severe valvular as well as myocardial involvement occur predominantly in the glycogen storage diseases, types II-IV, mucolipidoses, sphingolipidoses, and neuronal ceroid lipofuscinosis. There are a variety of neuromuscular disorders that may be associated with cardiomyopathy, including the muscular dystrophies, Friedreich's ataxia, and Kugelberg-Welander syndrome. The pathological features of these conditions are not specific, but result usually in a congestive form of cardiomyopathy. Patients with metal and pigment metabolic disorders include iron storage disease, either hemochromatosis or transfusional hemosiderosis, Menkes' kinky hair syndrome, and Dubin-Johnson syndrome. Either a restrictive or a congestive form of cardiomyopathy may occur. The systemic form of carnitine deficiency is an autosomal recessive disorder and may present as a cardiomyopathy with congestive heart failure and lipid accumulation in the myocardial cells. Connective tissue disorders are generalized diseases that may involve the heart and valvular tissue, but also the blood vessels. These include Marfan's syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, and pseudo xanthoma elasticum. PMID- 3333141 TI - Pathological features of Kawasaki disease (mucocutaneous lymph node syndrome). AB - Kawasaki disease (mucocutaneous lymph node syndrome) (MCLS) is an apparently infectious disease, an etiological agent of which has not been established, with peak age incidence at about 1 year, but with progressively fewer cases occurring into the fourth decade. Early clinical features include fever, rash, conjunctival injection, dry reddened lips, oropharyngeal reddening, enlarged cervical nodes, and swelling and redness of hands and feet. Peeling of skin of fingers and toes, arthralgia, and marked thrombocytosis are frequent 1-2 weeks after onset. Myocarditis, cardiac valvulitis, and lymphocytic or mixed interstitial infiltration of pancreas, renal, splenic, and hepatic hilar regions are seen in the early phase, but arteritis, typically of extraparenchymal arteries, is the most important aspect of MCLS, hence the term infantile periarteritis nodosa, formerly applied to fatal cases of MCLS. Thrombosis of coronary artery aneurysms is the most common cause of death (rate about 0.5%). The peak time of death is 3 4 weeks from onset, but death from coronary occlusion has been seen as late as 14 years after the acute phase. Aneurysmal rupture with hemopericardium or retroperitoneal hemorrhage is rare, as are late brachial, iliac, or other arterial aneurysms. Pathological features of MCLS in the early and later stages are described and illustrated, and the epidemiologic, etiologic, forensic, and other aspects of the disease are discussed. PMID- 3333142 TI - Arterial involvement in genetic diseases. AB - Whereas the information on the subject of arterial status is sketchy and haphazard with respect to any one genetic disorder, the number of these diseases would have precluded the provision of a critical review within the scope of this presentation. Thus, it was deemed more meaningful to approach the subject selectively. A brief summary was provided on the nature of the arterial wall and its involvement in genetic diseases either as a primary target or a secondarily affected organ, and on "affinity" of various genetic disorders for a type (elastic, muscular, or smallest), segment (proximal, distal), and layer (intimal, medial, adventitial) of the arterial tree or the arterial wall, respectively. Genetic diseases may affect arteries by "causing" (a) congenital malformations, (b) alteration of the arterial "makeup" without necessarily producing definable lesions, and (c) modification of a nongenetic arterial disease (e.g., atherosclerosis), or by "producing" (d) arterial lesions that are characteristic of (even specific for?) a given genetic disorder. A few examples were selected to illustrate (b) (tuberous sclerosis; infantile GM1-gangliosidosis), (c) Wolman's disease; familial hyperlipoproteinemias), and (d) [Hurler's disease, neurofibromatosis; Ehlers-Danlos syndrome (type IV)]. Whenever available, the results of electron microscopic studies carried out in our laboratories were included. Some of these have not been reported in the literature to date. The need for a coordinated multidisciplinary approach to the study of genetic diseases in general is stressed in closing. PMID- 3333143 TI - Constrictive and restrictive pulmonary hypertension in the newborn and infant. AB - The normal pulmonary circulation is constricted at birth and, as judged by its low arterial density, is relatively more restricted than in the older infant and child. During adaptation to air breathing, pulmonary arterial dilatation occurs rapidly, but also the compliance of the resistance arterial segment increases. In the fetus and newborn, the resistance segment is proximal to the respiratory or alveolar surface. Further expansion of the pulmonary vascular bed occurs by growth in size of lumen diameter of existing arteries and growth of new ones. Multiplication of alveoli and arteries is relatively dissociated--alveolar density can increase normally without normal vascular multiplication. Persistent pulmonary hypertension of the newborn occurs because of (1) lung hypoplasia associated with hypoplasia of the vascular bed, usually affecting both size and number of units, (2) abnormal muscularization of intraacinar arteries before birth, causing restriction of vascular volume, (3) failure of the adaptation programs, and (4) hyperreactivity. Immaturity of the circulation is apparent as hyperreactivity or "twitchiness": this can be superimposed on each of the other types. A hyperirritable vascular bed can cause a labile and then a fixed pulmonary hypertension that does not respond to dilators. PMID- 3333144 TI - A comparison of a hydrochlorothiazide plus triamterene combination (Dyazide) and atenolol in the treatment of patients with mild hypertension: a multicentre study in general practice. PMID- 3333146 TI - A double-blind study of Inderex in the treatment of essential hypertension. PMID- 3333145 TI - Assessment of left ventricular function and prognosis in survivors of acute myocardial infarction using Doppler ultrasound: a comparison with radionuclide ventriculography. PMID- 3333147 TI - Characteristics of osteoclast precursor-like cells grown from mouse bone marrow. AB - Cells resembling mononuclear osteoclast precursors (OCP-like) were grown from mouse bone marrow and subsequently studied for expression of macrophage-specific surface antigens (F4/80 and Mac-1), phagocytosis activity, and DNA synthesis. Expression of tartrate-resistant acid phosphatase (TRAcP) activity served as general marker for OCP-like cells. Mononuclear phagocytes, characterized by expression of tartrate-sensitive acid phosphatase (TSAcP) activity, were also grown from mouse bone marrow and were compared with OCP-like cells. TRAcP positive OCP-like cells showed low values for F4/80 and Mac-1 expression, as well as low phagocytosis activity. Macrophages (TSAcP+) showed very high values for expression of both surface antigens and for expression of phagocytosis activity, while osteoclasts (TRAcP+), reported to lack Ag F4/80, were also negative for Mac 1. DNA synthesis in OCP-like cells was low and resembled the values found in macrophages. Chase experiments after nuclear pulse labeling indicated that TRAcP positive OCP-like cells developed from immature proliferating progenitor cells which did not yet show TRAcP activity. These results show that TRAcP-positive OCP like cells have characteristics of both mononuclear phagocytes and osteoclasts. We propose that OCP-like cells are relatively late stages in an osteoclast specific cell lineage which diverges from the mononuclear phagocyte lineage. PMID- 3333148 TI - Carbohydrate metabolism in the critically ill patient. Implications for nutritional support. AB - Alterations in the metabolism of glucose occur in the critically ill patient. Because glucose is a central controlling factor in the metabolic state of the critically ill, a complete knowledge of both the metabolic changes and their physiologic implications is important in the clinical management of these patients. PMID- 3333149 TI - Protein metabolism and requirements in the critically ill patient. AB - The metabolic alterations of the critically ill patient greatly affect the processes of both protein synthesis and degradation as well as the nitrogen balance. It is important to understand these affects so that protein and nitrogen balance may be accounted for in parenteral nutritional support. PMID- 3333150 TI - Energy measurements and requirements of critically ill patients. AB - The energy expenditure of the critically ill patient is influenced by many factors, thus making it difficult to predict. Measurement of energy expenditure in mechanically ventilated patients receiving elevated oxygen concentrations requires a good understanding of the measurement technique and its limitations, whether it be the gas exchange or Fick method. More investigation is needed to better understand the determinants of energy expenditure, as well as the total energy requirements of the critically ill patient. PMID- 3333151 TI - Bonding agents improve porcelain repair. PMID- 3333152 TI - Increase in multiresistance of Shigella dysenteriae type 1 strain in Rwanda. PMID- 3333153 TI - A retrospective analysis of the occurrence of Shigella flexneri serotypes in some African countries. PMID- 3333154 TI - A retrospective study of the mortality from malaria during 1984-1985 at the Kenyatta National Hospital. PMID- 3333155 TI - Risk of transfusion malaria in Nairobi. PMID- 3333156 TI - Anti-inflammatory activity of superoxide dismutases: comparison of enzymes from different sources in different models in rats: mechanism of action. AB - Comparison of the anti-inflammatory properties of superoxide dismutases from different sources using different models (carrageenan and adriamycin induced inflammation, adjuvant-induced arthritis) in rats shows a very wide range of activity from extremely good to zero. Neither circulating life time nor intracellular penetration are of importance. The mechanism of biological activity of the SODs is discussed in detail, and binding to an interphase situation on the outer cell surface is postulated. As a consequence of these various considerations it is predicted that clinical application of human Cu-SOD in humans may well be much less spectacular than is commonly assumed, and indeed may be somewhat disappointing. PMID- 3333157 TI - An iron-messenger system--a hypothesis. PMID- 3333158 TI - [The bulla formation diseases in the maxillofacial region]. PMID- 3333159 TI - [Marginal fitness of adhesion-fixed partial dentures: scanning electron microscopic study]. PMID- 3333160 TI - [Clinical effects of the "Vacuum-Matic" attachment on retention of a maxillary complete denture]. PMID- 3333161 TI - [Removable partial dentures: Part 4. Dental caries and mobility of abutment teeth]. PMID- 3333162 TI - Placebo controlled double-blind study of pentoxifylline in sickle cell disease patients. AB - Sixty patients (37 males, 23 females, age range 7 to 34 years) suffering from sickle cell disease were treated with pentoxifylline (1200 mg/day per os, Trental 400 t.i.d.) or placebo in a double-blind randomized study of six week duration. Observation of pain frequency, intensity and duration of pain events as well as determination of various laboratory and hematologic parameters were maintained on weekly or biweekly basis, respectively, throughout the study. At the end of the trial the number of patients (14) with pain periods and the number of pain events (57) and the mean duration of pain events (4.1 days) in the drug group were significantly better than in the placebo group with 25 patients with pain, 219 pain events and 8.8 days mean pain duration. Hematocrit, red cell count, hemoglobin and platelet aggregation showed slight but significant positive changes with no corresponding alteration with placebo. The over all assessment of the therapeutic response showed 21 clearly improved patients with pentoxifylline compared to 10 such patients with placebo (p less than 0.05). Two patients on pentoxifylline and four on placebo experienced transient side effects of nausea and gastric intolerance. PMID- 3333163 TI - A hitherto unreported case of 21-hydroxylase deficiency associated with Bartter's syndrome and a balanced 6-9 translocation. AB - A description is given of a girl with the non-salt-losing type of congenital adrenal hyperplasia (CAH) and with Bartter's syndrome. In addition, the patient had a balanced translocation between 6q and 9p. Although the possibility cannot be ruled out fully that an excess of progesterone might modify the renin aldosterone axis to some extent, the finding that dexamethasone therapy improved the clinical features of CAH but failed to correct metabolic disorders in electrolyte balance strongly suggests the coexistence of the two clinical entities. Chloride transport at the distal tubule was impaired moderately in the patient, which suggests that her defective reabsorption of chloride was responsible for the impaired renal handling of sodium that is often observed in patients with Bartter's syndrome. It appears that the reciprocal translocation is unrelated to both CAH and Bartter's syndrome since the same translocation was found in her healthy mother and siblings. PMID- 3333164 TI - Neonatal bacterial endocarditis of the pulmonary valve: report of two cases. AB - Bacterial endocarditis in the neonate is rare and fatal in the majority of reported cases. This article reports two neonates who survived bacterial endocarditis. One patient was infected with group B beta-hemolytic streptococcus (GBBS) while the second grew Streptococcus saluvarius from the blood. PMID- 3333165 TI - Historical perspective of noninvasive monitoring. PMID- 3333166 TI - Physiology of oxygenation and its relation to pulse oximetry in neonates. PMID- 3333167 TI - The high risk infant: transitions in health, development, and family during the first years of life. AB - Greater numbers of preterm, low birth weight ("high risk") infants are surviving than ever before. It has become increasingly important for physicians and other health care professionals to become familiar with the many real and potential problems seen in this population of children during the first years of life and beyond. The residue of illnesses that are presented in the neonatal intensive care nursery and major health vulnerabilities of the early years are discussed in this article. Normal variations in neurodevelopmental patterns unique to preterm infants and neurodevelopmental disabilities which have a higher prevalence in this population are presented. The impact of a high risk infant on the family unit is described. Finally, resources and interventions available to the child, family, and health care provider during and following the transition from the hospital to home are reviewed. PMID- 3333168 TI - An unusual neonatal case presentation: Streptococcus pneumoniae pneumonia with abscess and pneumatocele formation. PMID- 3333169 TI - Comparison of hypnosis with conventional relaxation for antenatal and intrapartum use: a feasibility study in general practice. AB - A hypnosis programme for antenatal and intrapartum use has been developed and successfully introduced into a practice as an alternative to conventional relaxation training. Of 96 women from the practice who delivered during the 10 month period of the study 51 opted for the psychoprophylaxis and 45 for the hypnosis. Details of the pregnancy, labour and postnatal period were collected for both groups, together with a subjective assessment of their satisfaction with labour.Disparity between the ages and parity of the two groups made comparisons difficult. The duration of the first stage of labour was markedly reduced in the hypnosis group by 98 minutes for primiparas and 40 minutes for multiparas. A small (five minutes) increase in the length of the second stage may have been a result of the hypnotic relaxation. The verbalization has been amended accordingly. The hypnosis group were more satisfied with labour than the psychoprophylaxis group (mean satisfaction score 7.4 versus 5.6) and they reported other benefits of hypnosis, for example, reduction in anxiety and help with getting to sleep.Further studies are planned. PMID- 3333170 TI - Fibre-optics and optical sensors in medicine. PMID- 3333171 TI - Tocopherol in brain metabolism and disease: a review. PMID- 3333174 TI - [Results of computerized tomography of the head in pituitary dwarfism]. PMID- 3333173 TI - Intracellular pH determination by absorption spectrophotometry of neutral red. PMID- 3333175 TI - [Roentgenometric evaluation of the orbital content in thyroid-related ophthalmopathy by computerized tomography]. PMID- 3333177 TI - [Comparison of the diagnostic usefulness of Tc-HEPIDA and Tc 99m p-butyl-IDA complexes]. PMID- 3333176 TI - [Pheochromocytomas with extra-adrenal location]. PMID- 3333178 TI - [Polycystic renal dysplasia]. PMID- 3333172 TI - The role of the brain stem in generalized epileptic seizures. PMID- 3333179 TI - [Value of ultrasonic examination in the differential diagnosis of kidney diseases. I. Clinical studies]. PMID- 3333180 TI - [Comparison of 2 methods of galactography]. PMID- 3333181 TI - [Development and activities of the Institute of Radiology, Medical Academy, in Warsaw 1946-1986]. PMID- 3333183 TI - Oxygen radicals in cell injury and cell death. PMID- 3333182 TI - [Radiological image of barotrauma of the lungs in a frogman]. PMID- 3333184 TI - Phagocytosis: an overview. PMID- 3333185 TI - Late-acting components of complement: their molecular biochemistry, role in the host defense, and involvement in pathology. PMID- 3333186 TI - Is autoantibody production related to particular B-cell subsets and variable region genes? PMID- 3333187 TI - The role of ultraviolet radiation-induced cross-reactive tumor antigens in tumor immunity. PMID- 3333188 TI - Treatment of malignancy with unmodified antibody. PMID- 3333189 TI - Theme and variation in the control of exocytosis. PMID- 3333190 TI - Cytoplasmic free Ca2+ and the intracellular pH of lymphocytes. PMID- 3333191 TI - Mechanism of activation of protein kinase C: role of diacylglycerol and calcium second messengers. PMID- 3333193 TI - Multiple roles of calcium in anoxic-induced injury in renal proximal tubules. PMID- 3333192 TI - Membrane and microfilament organization and vasopressin action in transporting epithelia. PMID- 3333194 TI - The role of the plasma membrane and intracellular organelles in synaptosomal calcium regulation. PMID- 3333195 TI - Alterations in intracellular calcium produced by changes in intracellular sodium and intracellular pH. PMID- 3333196 TI - Calcium and magnesium movements in cells and the role of inositol trisphosphate in muscle. PMID- 3333197 TI - Localization of neuropeptide Y messenger ribonucleic acid in rat and mouse brain by in situ hybridization. AB - The distribution of neuropeptide Y (NPY) messenger ribonucleic acid (mRNA) in the rat and mouse brain has been examined. A 28-mer oligonucleotide probe complementary to a distinctive region of NPY mRNA was 3'-end labeled with [35S] deoxycytosine triphosphate ([35S]-dCTP) by using terminal transferase and was hybridized to fixed sections of rat and mouse brain. The hybridization of the labeled probe to the mRNA in the tissue section was then detected autoradiographically. A strong hybridization signal was seen corresponding to the arcuate nucleus of the hypothalamus. Scattered NPY-mRNA-containing cell bodies were seen throughout the cerebral cortex. Experiments which compared the distribution of NPY mRNA with immunohistochemically detected NPY indicated a similar distribution in the arcuate nucleus of the hypothalamus and cerebral cortex. These results indicate that active transcription of the NPY gene occurs within the brain and this transcription takes place in NPY-containing cell bodies. PMID- 3333198 TI - Recollections on the early concepts of the synapse. PMID- 3333199 TI - Comparative immunohistochemical demonstration of peptide F- and other enkephalin containing neurons in the enteric nervous system of the rat. AB - The immunohistochemical localization of peptide F and the related enkephalins met5-enkephalin (met-enk), leu5-enkephalin (leu-enk), met5-enkephalin-arg6-phe7 (met-enk-arg-phe), and met5-enkephalin-arg6-gly7-leu8 (met-enk-arg-gly-leu) was investigated by means of the indirect immunofluorescence technique in the enteric nervous system of the rat. Peptide F-like immunoreactivity was widely distributed within neuronal structures throughout the gastrointestinal (GI) tract of the rat. Peptide F-containing nerve cell bodies were mainly located in the myenteric plexus, and only rarely were seen in the submucosal plexus. Peptide F immunoreactive nerve fibers were principally present in the myenteric plexus and circular muscle layer; few were found in the submucosal plexus, longitudinal muscle layer, muscularis mucosa, and mucosa. No peptide F-containing fibers were found associated with blood vessels in the gut. By comparing the distribution of immunoreactive peptide F with other related enkephalins met-enk, leu-enk, met-enk arg-phe, and met-enk-arg-gly-leu, we observed that there was a remarkable similarity in the distribution of peptide F and other enkephalins in the GI tract. These data, combined with our previous studies, indicate that peptide F may coexist with other related enkephalins in the same neurons of the enteric nervous system. The results suggest that peptide F, a product of the proenkephalin A gene, may play a physiological role within the enteric nervous system. PMID- 3333200 TI - Effects of a behaviorally active LHRH fragment and septal area stimulation on the activity of mediobasal hypothalamic neurons. AB - The effect of Ac-LHRH, an LHRH fragment capable of facilitating lordosis, and LHRH on the firing rate of mediobasal hypothalamic neurons receiving input from the septal area, (a site containing the majority of LHRH perikarya) was studied via conventional extracellular recording techniques. A multibarrelled glass electrode assembly was lowered through the dorsomedial and ventromedial hypothalamus to detect single units responsive to septal area stimulation, and to iontophoretically apply Ac-LHRH and LHRH. Ovariectomized rats were primed with estradiol benzoate (EB; n = 21) or left untreated (n = 34) to determine if the neuronal responsiveness to septal area stimulation and/or to the two peptides was subject to estrogenic modulation. Of the total number of 228 neurons recorded in the study, 51 units (22.4%) were orthodromically responsive to septal area stimulation. The orthodromic responses in EB-primed animals (n = 20) were characterized by a short-latency, short-duration increase in membrane excitability. When spontaneous activity was sufficiently high, the excitatory response was followed by, or superimposed upon, an inhibitory response of longer duration. Similar orthodromic excitatory and inhibitory response characteristics were observed in 21 of the 31 neurons recorded in nonprimed animals. In the remaining ten neurons, however, the excitatory component was absent. Iontophoretic application of both Ac-LHRH and LHRH was found to produce predominantly an inhibitory effect on cell firing. Most neurons responded to the two peptides in a similar manner (i.e., inhibited by both peptides, excited by both peptides, or not effected by either peptide).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333201 TI - [Ground water fluorosis: detection of a new endemic focus. The significance of biological levels of fluoride]. PMID- 3333202 TI - [Pyogenic abscess of the liver. A retrospective study of 17 cases]. PMID- 3333203 TI - [Intrathoracic volvulus of the stomach in hiatal hernia. Apropos of a case]. PMID- 3333204 TI - William Liley and fetal transfusion: a perspective in fetal medicine. AB - The circumstances under which Sir William Liley, KCMG, first conceived the idea of blood transfusion to mitigate temporarily the effects of severe haemolytic disease in an affected fetus, and carried it to a successful conclusion, all in a former war-time American army hospital, are presented. The significance of his achievement is estimated as being, not so much a major advance in the management of a serious fetal disease (which if left to itself would eventually disappear, albeit in millennia), but a first real demonstration that the fetus is accessible to skilled diagnosis and treatment, and thus has the inalienable right to be as much regarded as a patient as anybody else. PMID- 3333205 TI - Fetal surgery: it has a past, has it a future? AB - The past history of fetal surgery is briefly reviewed. The current controversies revolving around the fetal treatment of hydrocephalus and obstructive uropathies (posterior urethral valves, prune belly syndrome, hydronephrosis) are compared and contrasted with the remarkably similar controversies that raged when fetal transfusions were first introduced. The future of fetal surgery is discussed in the light of the ethical issues raised by the prospect of fetal surgery and the rather disturbing medicolegal climate. There are already important legal precedents which will affect the field of fetal surgery. The strong opinion is expressed that fetal surgery must only remain an option offered to the mother and never forced upon her. PMID- 3333206 TI - A history of the treatment of hydrocephalus. AB - At a time when the intrauterine diagnosis of hydrocephalus is commonplace and pioneering efforts of antenatal therapy are evolving, review of the chronology of treatment of this disorder becomes pertinent. The history of therapy of hydrocephalus may be divided into three phases. The first two largely involved accumulation of basic anatomical and pathophysiological information. The last phase dates only from the 1950s and may be considered an era of rapid technical development. This account discloses the obligatory relationship between useful therapy and basic knowledge. PMID- 3333207 TI - Fetal tissue biopsy: techniques and indications. AB - A considerable variety of invasive intrauterine procedures has been developed in the last 15 years. This article describes techniques for obtaining fetal blood, skin, liver, tumour specimens and chorionic villi, and discusses their indications and risks. PMID- 3333208 TI - The foetus as a personality. By A.W. Liley, 1972. PMID- 3333209 TI - Ultrasonography in antenatal management: should it be a routine procedure? AB - Randomized clinical trials have not provided unequivocal justification for the routine use of ultrasound in antenatal management. Nonetheless, routine ultrasonography is widely practiced in many places, there is no evidence to suggest it is biologically harmful, and its diagnostic capabilities are being increasingly documented. There are, however, no studies of the clinical, psychological or economic benefits of routine ultrasound in clinically low-risk patients who would not normally be scanned. To avoid continuing uncertainty about the risks and benefits of routine ultrasound, randomized trials should be conducted of future developments in technique and procedure in places where routine scanning is common. In places which have not adopted routine scanning randomized trials could still answer fundamental questions about routine use of the technique. PMID- 3333210 TI - Ultrasound diagnosis of intrauterine growth retardation. AB - Intrauterine growth retardation is associated with increased perinatal morbidity and mortality. Assuming an accurately dated pregnancy, ultrasonic estimations of fetal weight can be used to predict intrauterine growth retardation. Antenatal detection of this condition will have an impact on management and ideally may improve outcome. PMID- 3333212 TI - Justice Harry A. Blackmun: the Supreme Court and the limits of medical privacy. PMID- 3333211 TI - Fetal therapy: ethical and legal implications of prenatal intervention and clinical application. AB - Recent advances in antenatal diagnosis have stimulated interest in the development of techniques for in utero treatment of fetal abnormalities. This article identifies and discusses the ethical and legal problems which emerge from fetal therapy. Is a fetus a patient? Does the fetus have rights? Who should give consent for the unborn? Does the fetus have redress if it is injured? Could a pregnant woman be forced to undergo treatment which could endanger her life and health for the benefit of the fetus? Answers to these questions are not clear and create in themselves additional queries. Until fetal therapy becomes an accepted medical practice, the resolution of the ethical and legal issues that it provokes will probably remain inconclusive and a matter of concern. PMID- 3333213 TI - A tribute to Justice Harry A. Blackmun. PMID- 3333214 TI - "So quick bright things come to confusion". PMID- 3333215 TI - Gestational burdens and fetal status: justifying Roe v. Wade. PMID- 3333216 TI - The impact of medical technology on the pregnant woman's right to privacy. PMID- 3333217 TI - Biology and the Bill of Rights: can science reframe the Constitution? PMID- 3333218 TI - Justice Blackmun: a survey of his decisions in psychiatry and law. PMID- 3333219 TI - Rebalancing the medical triad: Justice Blackmun's contributions to law and medicine. PMID- 3333220 TI - [Acquired and congenital antithrombin III deficiency. Discussion of a clinical case]. PMID- 3333221 TI - [The effect of abraded enamel on the retention of cast metal resin bonded bridges]. PMID- 3333222 TI - [Comparison of the effects of different curing systems on the tensile bond strength of resin veneers to cast alloys]. PMID- 3333224 TI - Periodontal considerations of endosseous implants: a philosophy for understanding the tissue-implant interface. PMID- 3333223 TI - [Immunology of periodontal diseases]. PMID- 3333225 TI - Hydroxylapatite and its role in ridge augmentation and preservation. PMID- 3333227 TI - Prosthetic restorations and the oral tissues. PMID- 3333228 TI - The distal extension saddle partial denture. A review. PMID- 3333226 TI - Posterior composite resin restorations--a review of clinical problems. PMID- 3333229 TI - The role of connective tissue in the temporomandibular joint. PMID- 3333230 TI - O-antigenic heterogeneity of Eikenella corrodens lipopolysaccharide. PMID- 3333231 TI - Bonding of amalgam filling to tooth cavity with adhesive resin. PMID- 3333232 TI - The adhesion mechanism of dental adhesive resin to the alloy. Experimental evidence of the deterioration of bonding ability due to adsorbed water on the oxide layer. PMID- 3333233 TI - Studies on adhesion to tooth substrate. II. Synthesis and adhesiveness of monomers that have amide groups. PMID- 3333234 TI - Bond strength between amalgam and tooth hard tissues with application of fluoride, glass ionomer cement and adhesive resin cement in various combinations. PMID- 3333235 TI - Pure titanium prefabricated post--compatibility with cast metal core. PMID- 3333236 TI - Effect of composition and curing type of composite on adaptation to dentin cavity wall. PMID- 3333238 TI - [Ultrasonic diagnosis of expansive lesions of the kidneys]. PMID- 3333237 TI - Bond strength of organic cements to tooth structure--effect of various mordants on bonding to dentin. PMID- 3333239 TI - [Study of the effect of force on the lower cuspids produced by a partial denture]. PMID- 3333241 TI - Denture wearer's self assessment of vertical dimension. PMID- 3333240 TI - [The occurrence and importance of fungi of the Candida species in the etiology of chronic tonsillitis]. PMID- 3333243 TI - Rheumatic fever: a challenge. PMID- 3333242 TI - Ethical issues in geriatric dentistry. PMID- 3333244 TI - Pulmonary artery involvement in aorto-arteritis. PMID- 3333245 TI - Therapeutic double blind study of Gallopamil in patients with reproducible stable angina pectoris. PMID- 3333246 TI - Osteoclastoma of metacarpal bone (a case report). PMID- 3333247 TI - Psychological distress of Holocaust survivors and offspring in Israel, forty years later: a review. PMID- 3333248 TI - Psychoanalysis without shame. PMID- 3333249 TI - Assisting the parent of a child with asthma. AB - The parents of an asthmatic child are frequently faced with complex decisions that have to take into account the child's asthma as well as more general developmental needs. At times these parents may feel overwhelmed and doubt their ability to make reasonable decisions. If there is discomfort with some aspect of the treatment plan, the parents may remain silent. Denial, minimization, anger, withdrawal and noncompliance may occur. This paper offers suggestions for practicing pediatricians in regard to helping parents cope more effectively with childhood asthma. Specific issues dealt with are discipline, school issues, athletic participation, maintenance of the child's peer relationships, avoiding parental conflict, the use of support systems, behavioral aspects of medical management, and when to refer for psychiatric consultation. PMID- 3333250 TI - Antihistamines in asthma. AB - Reports in the literature have suggested that antihistamines are contraindicated in asthma because they dry the secretions in the upper and lower respiratory tracts. However, the consensus is that this is not the case. There may be a subset of asthmatics who report wheezing and a feeling of tightness in the chest after taking antihistamines but most of those who have severe perennial allergic rhinitis do not have adverse reactions and indeed benefit considerably from antihistamines. PMID- 3333252 TI - Character pathology in the elderly. PMID- 3333251 TI - The rhythms of asthma. PMID- 3333253 TI - [Correction of kinesiographic signals: application of sensitivity analysis method to the GMDH model for the correction of interlattice coordinates]. PMID- 3333254 TI - Ten-year survey of positive blood cultures among admissions to a neonatal intensive care unit. AB - A 10-year survey of positive blood cultures was conducted among 6,616 infants admitted to an intensive care unit from 1974-1983. Group B streptococci (59) and E. coli (32) were the most common pathogenic organisms isolated from the early onset group (less than 72 hours of age). The percentage of infants with bacteremia, the birth weight distribution of infected infants, and the organisms isolated did not change in the early onset group throughout the study period. Coagulase negative staphylococci (471), S. aureus (126), E. coli (33), Klebsiella sp. (30), and enterococci (30) were the most frequent organisms isolated from the late onset group. The frequency of infection in the late onset group did not change as a function of time but was associated with decreasing birth weight during the study period. Methicillin and gentamicin resistance among coagulase negative staphylococci preceded that of S. aureus by one to three years, suggesting interspecies transfer of bacterial resistance among staphylococci. The data indicate that whereas the epidemiology of early-onset septicemia has remained relatively stable during the study period, the incidence of late onset bacteremia is increasing with improved survival rates of low birth weight infants. Antibiotic administration in the late onset group should include consideration of hospital-acquired, multiply antibiotic resistant organisms as well as maternally-acquired bacterial flora. PMID- 3333255 TI - Kernicterus in the premature neonate. PMID- 3333256 TI - Infantile apnea, home monitoring, and SIDS: go back to go. PMID- 3333257 TI - [Prognosis and surgical problems of mitral valve prolapse]. PMID- 3333258 TI - Mitral valve prolapse syndrome: evidence of autonomic dysfunction. PMID- 3333259 TI - [Pathology of mitral valve prolapse]. PMID- 3333260 TI - The role of opsonins and opsonic antibody in the prevention and treatment of neonatal infections. PMID- 3333261 TI - Exchange transfusion in neonatal sepsis. PMID- 3333262 TI - Modulation of neutrophil mediated pulmonary damage: lessons learned from clinical disorders of neutrophils. PMID- 3333264 TI - Diseases most commonly transmitted by blood transfusion to the neonate. PMID- 3333263 TI - Neutrophil kinetics in the fetus and neonate and the clinical utility of granulocyte transfusion in neonatal medicine. PMID- 3333265 TI - Congenital and acquired defects in coagulation: diagnosis and treatment. PMID- 3333266 TI - Clinical indications for the use of blood products in potentially infected neonates. PMID- 3333267 TI - Therapeutic indications for platelets, plasma and plasma derivatives in the neonate. PMID- 3333269 TI - Mitogenic stimulation may induce an anti-mutagenic repair system in human lymphocytes. AB - The effect of mitogenic stimulation prior to X-irradiation was studied in human lymphocytes using a cloning technique. The hypoxanthine phosphoribosyltransferase locus was monitored and mutant cells were selected by their ability to form a clone in the presence of 6-thioguanine. Survival and mutagenesis were studied for cells irradiated before phytohaemagglutinin (PHA) stimulation and 1-7 days after PHA stimulation. Prior mitogenic stimulation had no effect on the decreasing survival observed with increasing X-ray dose. The mean mutation frequency of unirradiated cells ranged from 1.8 x 10(-6) to 3.3 x 10(-6). Cells irradiated and then stimulated with PHA showed an increase in mutation frequency with increasing dose of X-rays, up to 9.5 x 10(-5) after 400 rad, but mitogenic stimulation with PHA on days 2 or 3 before irradiation completely, and on days 1, 5 or 7 almost completely, prevented induction of mutations by 300 rad. These results suggest that mitogenic stimulation activates an anti-mutagenic system which prevents pre mutational lesions produced by X-irradiation being transformed into mutations. The lack of effect of PHA stimulation on survival suggests that the types of damage leading to mutations and lethality are different. PMID- 3333268 TI - Organic solvents inhibit the mutagenicity of promutagens dimethylnitrosamine and methylbutylnitrosamine in a higher plant Arabidopsis thaliana. AB - The organic solvents dimethylsulphoxide (DMSO), acetone, ethanol and dimethylformamide inhibited the mutagenic activity of the promutagens dimethylnitrosamine and methylbutylnitrosamine in a higher plant Arabidopsis thaliana. In contrast, the direct-acting mutagens N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) were not affected by the organic solvents (with the exception of DMSO). The effect of DMSO on MNNG- and MNU-mutagenesis is explained by its effect on the pH of the mutagenic solution. The results support the assumption that the activation of promutagenic nitrosamines in A. thaliana proceeds by the same, or similar, mechanisms to that in 'animal' activation. PMID- 3333270 TI - Effects of X-rays on the induction of somatic mutations and growth in the retinal pigmented epithelium during development of the mouse eye. AB - The coat and eye colour mutant beige (bg) leads to the production of distinctive retinal melanocytes with abnormally large pigment granules. Heterozygotes for bg were given 2 Gy acute X-irradiation at various times between day 11.5 of fetal life and 3 days after birth, at which age whole mounts were prepared of the retinal pigmented epithelium (RPE). These were scanned for the presence of mutant retinal melanocytes with large granules, either as single cells or as clones. The earlier the fetal irradiation, the greater was the effect on RPE area at 3 days post-partum (p.p.), which fell to about half normal with the 11.5-day fetal exposures. However, the ultimate size of the retinal melanocytes seemed little affected by the irradiation, although their normal size increased approximately 3 fold between 12.5 days post-coitum (p.c.) and 3 days p.p. Mean numbers of mutant melanocytes per eye were markedly higher than in +/bg controls at all irradiation ages other than 3 days p.p.; when allowance was made for final sizes of irradiated RPE's mutation frequencies fell steadily from 30.0 x 10(-5) at 11.5 days p.c. to 1.0 x 10(-5) at 3 days p.p., with 0.8 x 10(-5) in +/bg and 0.1 x 10( 5) in +/+ controls. The doubling dose of 0.18 Gy at 16.5 days p.c. was similar to that found at 17.5 days p.c. in a previous somatic mutation experiment in which follicular melanocytes were scanned for mutations at different (d and ln) loci.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333271 TI - Genetic effects of methylmethanesulphonate during meiosis in Saccharomyces cerevisiae. AB - Enhanced mutagenic action after methylmethanesulphonate (MMS) treatment was found in pre-replicative meiotic yeast cells of the strain D7. The level of gene conversion after MMS treatment rose above the spontaneous level during the period of commitment to meiotic recombination, but at later times into meiosis became indistinguishable from the full meiotic level. In contrast reciprocal recombination detected between ade 2 and the centromere of chromosome XV after MMS treatment remained above the spontaneous level up to commitment to meiotic cell division with relatively high levels through meiotic prophase I. These results are discussed in relation to MMS-induced damage and its repair, particularly double-strand break repair. PMID- 3333272 TI - The mutagenicity of sodium fluoride to L5178Y [wild-type and TK+/- (3.7.2c)] mouse lymphoma cells. AB - L5178Y wild-type and TK+/- (3.7.2c) cells were treated with sodium fluoride over a range of concentrations (10-500 micrograms ml-1) and treatment times (4, 16 and 48 h) covering less than 10-100% survival. The mutant frequency at five genetic loci (resistance to ouabain, 6-thioguanine, excess thymidine, methotrexate and 1 beta-D-arabinofuranosyl cytosine) was assayed in wild-type cells and trifluorothymidine in TK+/- cells. No significant induced mutation at any locus was observed after 4 h of treatment. Sixteen hours of treatment with high concentrations of sodium fluoride did not induce resistance to ouabain, but resulted in some significant induction of 6-thioguanine, 1-beta-D arabinofuranosyl cytosine and methotrexate resistance, although the results were variable between experiments and no dose-response was observed. At the thymidine kinase locus, a dose-related increase in mutant frequency to excess thymidine and trifluorothymidine resistance was observed. The maximum induction was approximately eight times the control frequency after TK+/- cells were treated with the highly toxic concentration of 500 micrograms ml-1 of sodium fluoride for 16 h. These observations, and an analysis of the colony size of trifluorothymidine-resistant mutants in TK+/- cells, suggest that sodium fluoride is clastogenic to dividing cultured mammalian cells at high, toxic concentrations. Further work is desirable to investigate the mechanism by which chromosomes are damaged at high concentrations of fluoride, since without such a mechanistic understanding, extrapolation of our data to the human situation must be insecure. Nevertheless, the knowledge available at present gives no reason to expect any genotoxic effects in human tissues at levels of fluoride ions to which they are currently exposed in the general population. PMID- 3333273 TI - Cell transformation: the role of oncogenes and growth factors. AB - An attempt is made to draw together diverse areas of biological research which have recently converged and opened up new experimental approaches to understanding the nature of cancer. In particular, the powerful techniques of molecular biology have been brought to bear on tissue culture systems. The case is made for the continued use of cell transformation in vitro as a real and useful model for cancer development. The hallmark of all cancer cells is loss of control over the cell cycle and the cellular elements involved, growth factors, growth factor receptors and signal transducers have been identified and in some instances shown to be encoded in cellular oncogenes. Moreover, as the molecular mechanisms underlying cell growth control are unravelled, those aspects involved in neoplastic change will be identified and this will lead to the development of definitive short-term tests for the detection of chemical carcinogens. PMID- 3333274 TI - Cytogenetic effects induced by alkylated guanine in mammalian cells. AB - Cytogenetic effects of O6-ethylguanine (O6EtG) were investigated in V79 Chinese hamster cells and human lymphocytes. The frequency of micronuclei and of polyploid cells was increased in a dose-dependent manner in V79 cells. Micronuclei were larger than those induced by the alkylating agent diethylsulfate, suggesting that they originated from chromosome loss rather than from chromosome breakage. Chromosome displacement was also observed and further indicated damage to the spindle. In human lymphocytes, both aneuploidy and polyploidy were induced. O6EtG did not induce either micronuclei or polyploidy in a V79 derivative, deficient in hypoxanthine-guanine phosphoribosyl transferase, suggesting that conversion of the base to a nucleotide is necessary. Preliminary data indicated that 7-ethylguanine was also able to induce aneuploidy and polyploidy in lymphocytes, although it was barely active in V79 cells. The hypothesis proposed is that alkylated nucleotides may behave as spindle poisons. As a consequence, treatment of mammalian cells with alkylating agents may induce numerical chromosome aberrations via alkylation of guanine nucleotide pools, a pathway which has not so far been proposed. PMID- 3333275 TI - A sensitive and quantitative enzyme-linked immunosorbence assay for the c-myc and N-myc oncoproteins. AB - The c-myc and N-myc nuclear oncoproteins are implicated in the genesis and maintenance of the transformed phenotype in several types of neoplastic disease, and the c-myc protein is involved in the progression of normal cells through the cell cycle. We have designed and developed sensitive and quantitative ELISAs for these proteins. Myc proteins are captured from cell lysates by an antibody directed against a peptide sequence substantially conserved in all known myc proteins; the captured proteins are recognised by a specific anti-c-myc or anti-N myc monoclonal antibody conjugated to alkaline phosphatase; bound alkaline phosphatase is measured with an extremely sensitive cycling enzyme system that generates a coloured end-product. The c-myc assay is calibrated using bacterially expressed human c-myc protein. We have used this assay to estimate the number of c-myc molecules in a range of normal and transformed cells of human, murine, and feline origin; to monitor increases in c-myc expression when quiescent cells are stimulated with growth factors; and to follow the decrease in c-myc protein levels when HL60 promyelocytic leukaemia cells are induced to differentiate with dimethylsulphoxide or phorbol esters. PMID- 3333276 TI - Diet for diabetics--a critical review. PMID- 3333277 TI - Demystifying the treatment of diabetes. PMID- 3333278 TI - Some common questions that insulin-dependent diabetics ask. PMID- 3333279 TI - Radiological investigations of the chest, breast, head & neck. PMID- 3333280 TI - Psychosomatics for all--past, present and future. AB - It used to be fashionable to begin consideration of psychosomatics about philosophy of mind and body. Nowadays it is a topic about health and practical care of patients--principally about the psychological aspects of any illness. Pathogenesis is becoming understood with some risk factors clearly identifiable. The high incidence of symptoms attributable to emotional disturbance has now been described in so many conditions that it is altering the delivery of health services. The boundaries of psychosomatics are extending. No longer is the topic confined to a few chronic diseases, even including new ones like AIDS, but it now includes support for carers and education about behaviour for health, to name two currently important aspects. The responsibility for the biopsychosocial approach does not lie alone with doctors, and certainly not only psychiatrists, but the many professionals involved in clinical care. The aim is not simply reducing symptoms, but improving functional capabilities and preventing social disadvantage. The more the advance of knowledge, the more intriguing become the questions awaiting answers. The risk factors due to predisposition or unhealthy behaviour and stress still only account for a small contribution to aetiology. Coping mechanisms, whether in personality or social support, still defy enough understanding to predict which patients will develop emotional disturbance, and which patients will respond to appropriate treatment. Perhaps, the most intriguing question is why, when certain relevant facts about unhealthy behaviour are beyond dispute, such as the effect of drinking excessive alcohol, smoking nicotine, having unsafe sex, poor family caring or receiving insensitive treatment, it remains so difficult to bring about improvement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333281 TI - Recommendations for clinical studies in psychosomatic medicine. AB - To minimize discrepancies that may arise in clinical studies concerned with psychosomatic medicine, a set of methodologic recommendations was developed. Issues in design, sampling, collection of data and statistical inference are discussed. PMID- 3333282 TI - International trends of therapy and research in psychosomatic medicine. AB - Against the background of the holistic concept of illness trends of psychosomatic therapy and research are identified in major countries. Different countries tend to concentrate on different aspects of research or praxis based largely on their compatibility with cultural or social assumptions of illness. The psychotherapies, behavioral medicine, social therapies and biological approaches are underscored in a given country and even within the same country competing therapies strive for hegemony. Problems and limitations of the reductionistic versus the holistic approaches in psychosomatic research are highlighted. PMID- 3333283 TI - Some unexplored regions of psychosomatic medicine. AB - The history of psychosomatic medicine in the 20th century is predominantly marked by a concern with studies of major diseases (e.g., angina pectoris, bronchial asthma, diabetes mellitus, essential hypertension, neurodermatitis, rheumatoid arthritis, etc.). Traditional physicians also narrowly focus on disease--a trend that began with Morgagni in the 18th century. But disease (defined by structural alterations) is not the only cause of illness and disability. In fact, most persons seeking health care are ill without having a disease. It is only recently that this distinction has been fully made. The various manifestations of ill health go by a variety of descriptive names--the functional or irritable bowel and hyperventilation syndromes, fibromyositis, psychophysiological, functional and somatoform or somatization disorders. They lead to loss of productivity, cost the health care system excessively, produce negative reactions in physicians, and are fertile ground for iatrogenic disease. They do not constitute discrete syndromes but overlap, each also being closely associated with anxiety and depression, sleep disturbances or marital disruption. They are the manifestations of sick persons not only of disturbances of bodily systems. They may be precipitated by unemployment, marital discord, bereavement, and job dissatisfaction. Curiously, ill-health has not been the major area of investigative interest of psychosomatic medicine. This presentation will emphasize why it should be, and why proper interventions may radically reduce the cost of medical care, prevent iatrogenic disease, and reduce the use of ill advised procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333284 TI - Somatization: the experience and communication of psychological distress as somatic symptoms. AB - Somatization implies a tendency to experience and communicate psychological distress in the form of somatic symptoms and to seek medical help for them. So defined, it is neither a disorder nor a diagnostic category but a generic term for a set of experimental, cognitive, and behavioral characteristics of patients who complain of physical symptoms in the absence of relevant medical findings. Such patients are ubiquitous in all medical care settings, pose difficult diagnostic and management problems, and overutilize health care thus contributing to its cost. Somatization may be transient or persistent, and may or may not be associated with a diagnosable medical or psychiatric disorder. The most common concurrence of somatization is with affective and anxiety disorders, and, to a lesser degree, the somatoform disorders. Persistent somatization poses a serious clinical, social, and economic problem and hence early identification of potential chronic somatizers should be attempted to avoid its development. Pain, fatigue, dizziness, and dyspnea are the commonest symptoms. Etiology of somatization is multifactorial and so should be its management. PMID- 3333285 TI - The meaning of stress, anxiety and collective panic in clinical settings. AB - The physician is often confronted with questions about the meaning of symptoms or diseases. One of the tasks of those practicing psychosomatic medicine is to delve into the answers to these questions. Anxiety is a common phenomenon in everyday practice, and it is evoked in the most different situations. The relationships of this kind of anxiety (i.e. when having to consider painful or life-threatening diseases or medical or surgical procedures) to both neurotic anxiety and normal anxiety (i.e. the one expressed in poetry or artistic creativity or present in the biographies of outstanding men and women who by no means could be considered as psychiatric cases) leads to define anxiety as the psychological equivalent of stress. Anxiety is the unspecific response to a threat induced by too sudden or too extreme variations in the environment (life changes, stressful situations, life events). Such mechanisms, so important for survival, can become self destructive, paving the way for the appearance of diseases represented by unsuccessful coping mechanisms. The analogy with the diseases of the general adaptation syndrome of Selye (i.e. autoimmune diseases) and with reactions in collective panics in disasters becomes evident under this perspective. The physician has to face anxiety with the same attitude that he faces pain, that is to say, going beyond a consideration of its 'normality' (it is quite normal to feel chest pain in acute heart infarct), keeping in mind its role in survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333286 TI - On desire, excitement, and impotence in modern sex therapy. AB - The widely accepted DSM-III classification of sexual dysfunctions has reinforced the idea that it concerns easily distinguishable deficiencies in the 'normal' phases of the sex response cycle: desire, excitement, and orgasm. For each of these deficiencies sex therapists offer a standard treatment package by which clients can learn to restore the 'natural' response pattern. As such, treatment has become a matter of techniques and so has sexuality itself. Acting as psychotechnologists, many sex therapists show an almost insatiable 'desire' to improve their clients' sexual performance and they experience the 'excitement' of their therapeutic work in counting the number of orgasms their clients are able to reach. But facing the problem of inhibited sexual desire, a lot of sex therapists must admist their 'impotence' in this matter. What they do not seem to realize is that their performance-oriented approach enhances a sociocultural climate in which people lose interest in preprogrammed sex, because sexual lust has turned from a taboo into a 'must'. PMID- 3333287 TI - Psychotherapy outcome research with bulimia nervosa. AB - Recent psychotherapy studies for bulimia nervosa are reviewed and it is concluded that many interventions lead to statistically and clinically significant reductions in the frequency of bingeing and vomiting and other associated symptoms; however, the results are more variable if success is defined as abstinence from symptomatic behavior. Treatment and patient variables which seem to be associated with positive response to treatment are reviewed and serious methodological concerns are raised. Carefully controlled dismantling trials are recommended in order to isolate factors which are critical for symptom change. PMID- 3333288 TI - Criteria for diagnosing depression in the setting of medical disease. AB - The evaluation of depression in the setting of medical disease is a complex task that requires considerable clinical skills. Physical illness is a common cause of psychopathology and this should alert the physician to vigorously search for possible organic explanations of depressive symptoms, especially in the elderly, where organic affective syndromes seem to be most prevalent. The multifactorial determinants and modes of expression of depression in the medically ill require further psychosomatic studies. PMID- 3333289 TI - Psychosomatic aspects of liver transplantation. AB - Forty patients received orthotopic liver transplants at Massachusetts General Hospital between May 21, 1983 and July 21, 1987 (mean follow-up: 64 weeks, range: 2-186 weeks). Twenty-seven patients (68%) were living as of July 21. Among survivors, 15 (56%) returned to full activity; and 7 (26%) were partially rehabilitated. Five patients were rehospitalized or recently transplanted. Successful outcome occurred most often among those who came to transplant early in the course of illness. All adults experienced preoperative anxiety and 17 (50%) of adults had some degree of hepatic encephalopathy. Following operation, 8 adults (24%) were referred for treatment of depressive disorder typically associated with deterioration of hepatic status, infectious complication or recurrence of cancer. Medical noncompliance required psychiatric intervention in 3 cases. Other psychiatric events an increasingly successful intervention of major scope and affords meaningful survival to many patients whose liver disease allow less than a year of life. Psychiatric consultation is an essential support to the transplant program. PMID- 3333290 TI - Discomfort or disability in patients with chronic pain syndrome. AB - In the present study of 253 patients with chronic pain syndrome we have made a multidimensional approach. All patients have been included in the study independent of coexisting states of anxiety or depression. We included criteria for diagnosis, duration, generability and intensity of pain, anxiety and depression, psychosocial stressors and social functioning. Using this system we have evaluated the antipain effectiveness of clomipramine and mianserin in a double-blind, placebo-controlled trial. By use of the Melancholia Scale 16 patients (6%) had a major depression, and by use of the Hamilton Anxiety Scale, 72 patients (28%) had a generalized anxiety disorder. The results showed no statistically significant difference between the three treatments, when using a visual analogue scale (VAS 10 cm with cut-off score 2 cm) for severity of pains as outcome criteria or the results of VAS and Global Clinical Impression Scale using the criteria of reduction of 50% or more between the pretreatment and posttreatment scores. By use of all the assessments it is possible to make an improvement curve for each patient expressed by the area under the curve, and not even there we found a difference between the three treatments. Clomipramine and mianserin were significantly superior to placebo in the topographical pain subgroup with headache using area under the improvement curves as criteria (p less than 0.05). When the 60-item General Health Questionnaire was used to identify minor psychiatric morbidity 44% was found. We can use this as a measure of quality of life. Our results have indicated that placebo-controlled studies are still needed in this field of research. PMID- 3333291 TI - Future directions in consultation-liaison psychiatry. AB - Consultation-liaison psychiatry in the United States has had to reassess its priorities with the change in health care economics in the 80 s. Liaison programs and educational programs for primary care staff are jeopardized. The emphasis has shifted from liaison to reimbursable consultation activities. Hospital stays are shorter with emphasis on outpatient and prepaid settings. Less expensive health care professionals are often asked to see patients previously evaluated by psychiatrists. This paper will discuss the need for focused cost-effective liaison services in this climate. Funding strategies for consultation-liaison programs, models of staffing consultation-liaison services, continuity of care from inpatient to outpatient services, integration of consultation-liaison psychiatrists in prepaid health care settings, primary-care educational programs, and psychosocial intervention programs for high-risk primary-care patients will be discussed. PMID- 3333292 TI - Developments in liaison psychiatry in the United Kingdom. AB - This paper reviews the organisation of liaison psychiatry in the United Kingdom and discusses the range of clinical problems which liaison psychiatrists undertake. It is suggested that, if services are to expand, more controlled intervention studies must be carried out to evaluate the effectiveness of psychiatry in a general medical setting. PMID- 3333293 TI - Medical-psychiatric service. AB - Recently, some American general hospitals have organized medical-psychiatric units for patients with concomitant medical and psychiatric disorder. These services have attracted considerable interest for their psychosomatic features, namely the treatment of patients who require acute hospital care and cannot be managed adequately either in a standard psychiatric unit or in the medical surgical wards of the general hospital. In due course, however, as often happens with innovations, the establishment of medical-psychiatric units has also come in for criticism and evaluation. Different models of medical-psychiatric services are discussed and compared. PMID- 3333294 TI - [Organ transplant from cadaver donor: organization of centers of procurement and distribution]. PMID- 3333295 TI - [Immunosuppressive measures in renal transplantation]. PMID- 3333296 TI - [Cyclosporin: new acquisition in transplant immunosuppression]. PMID- 3333297 TI - [Infection in recipients of kidney transplants]. PMID- 3333298 TI - [kidney transplant: criteria for the selection of donors]. PMID- 3333299 TI - Mechanism of inactivation of UDP-glucose 4-epimerase from Saccharomyces cerevisiae by D-xylose and L-arabinose. AB - In a previous paper (Carmenes et al., 1984) we reported that UDP-glucose 4 epimerase from Saccharomyces was inactivated both in vivo and in vitro (crude extracts) by L-arabinose or D-xylose. In this paper, we report that pure epimerase requires the presence of UMP or UDP to be inactivated by sugars and that the inactivation is due to the reduction of the epimerase NAD+, which is essential for epimerase activity. The inactivation rate is directly proportional to epimerase and sugar concentrations and hyperbolically proportional to UMP concentration. In situ experiments made with permeabilized cells showed that epimerase is inactivated in the same way when it is inside the cell. In vivo studies showed that epimerase is inactivated to a smaller extent when 1% D galactose is present in the culture medium than when 1% ethanol is the main carbon source. PMID- 3333300 TI - A comparative radiorespirometric study of glucose metabolism in yeasts. AB - A comparative radiorespirometric study of glucose metabolism in glucose-limited chemostat cultures of Saccharomyces cerevisiae, Candida utilis and Rhodosporidium toruloides was performed in an attempt to estimate the contribution of the hexose monophosphate (HMP) pathway to glucose metabolism. Radioactively labelled glucose was administered directly to the cultures in a constant substrate feed, without disturbance of the steady state. The 14CO2 yields from [1-14C]- and [6-14C] glucose demonstrated that the HMP pathway activities for the three yeasts were very similar. Furthermore, a quantitative analysis of results indicated that the HMP pathway activities were close to the theoretical minimum needed to cover the NADPH requirement for biomass formation. PMID- 3333301 TI - Alcoholic fermentation by 'non-fermentative' yeasts. AB - All type strains of 'non-fermentative' yeasts, available in the culture collection of the Centraalbureau voor Schimmelcultures, were reinvestigated for their capacity to ferment glucose in the classical Durham tube test. Although visible gas production was absent, nearly all strains produced significant amounts of ethanol under the test conditions. Under conditions of oxygen-limited growth, even strong alcoholic fermentation may occur in a number of yeasts hitherto considered as non-fermentative. Thus, shake-flask cultures of Hansenula nonfermentans and Candida silvae fermented more than half of the available sugar to ethanol. It is concluded that the taxonomic test for fermentation capacity, which relies on detection of gas formation in Durham tubes, is not reliable for a physiological classification of yeasts as fermentative and non-fermentative species. PMID- 3333302 TI - Cloning and sequencing of the PHO80 gene and CEN15 of Saccharomyces cerevisiae. AB - The PHO80 gene, which is one of the regulatory genes exerting negative control in the pho system of Saccharomyces cerevisiae, was cloned. The 1.8 kb DNA fragment carrying the PHO80 gene was sequenced and one open reading frame large enough to encode 293 amino acids was found in the sequence. Northern blot analysis of poly(A)+-RNA isolated from cells grown under repressed and derepressed conditions revealed that (i) the size of the PHO80 message was around 1.4 kb, (ii) the expression of the PHO80 gene was not affected by the presence or absence of inorganic phosphate in the medium, and (iii) the expression of the PHO80 gene was not affected by pho2, pho4, pho81, or by pho80 itself. A centromere sequence was found downstream of the PHO80 coding region. PMID- 3333303 TI - Ty, an endogenous retrovirus of yeast? PMID- 3333304 TI - Linear DNA killer plasmids from the yeast Kluyveromyces. PMID- 3333305 TI - Yeast/E. coli shuttle vectors with multiple unique restriction sites. AB - Two yeast/E. coli shuttle vectors have been constructed. The two vectors, YEp351 and YEp352, have the following properties: (1) they can replicate autonomously in Saccharomyces cerevisiae and in E. coli; (2) they contain the beta-lactamase gene and confer ampicillin resistance to E. coli; (3) they contain the entire sequence of pUC18; (4) all ten restriction sites of the multiple cloning region of pUC18 including EcoRI, SacI, KpnI, SmaI, BamHI, XbaI, SalI, PstI, SphI and HindIII are unique in YEp352; these sites are also unique in YEp351 except for EcoRI and KpnI, which occur twice; (5) recombinant plasmids with DNA inserts in the multiple cloning region of YEp351 and YEp352 can be recognised by loss of beta galactosidase function in appropriate E. coli hosts; (6) YEp351 and YEp352 contain the yeast LEU2 and URA3 genes, respectively, allowing for selection of these auxotrophic markers in yeast and E. coli; (7) both plasmids are retained with high frequency in yeast grown under non-selective conditions indicative of high plasmid copy number. The above properties make the shuttle vectors suitable for construction of yeast genomic libraries and for cloning of DNA fragments defined by a large number of different restriction sites. The two vectors have been further modified by deletion of the sequences necessary for autonomous replication in yeast. The derivative plasmids YIp351 and YIp352 can therefore be used to integrate specific sequences into yeast chromosomal DNA. PMID- 3333306 TI - Mutations in ARS1 increase the rate of simple loss of plasmids in Saccharomyces cerevisiae. AB - Autonomously replicating sequence (ARS) elements are DNA sequences that promote extrachromosomal maintenance of plasmids in yeast. Mutations generated in vitro in the ARS1 region were examined for their effect on plasmid maintenance in a yeast centromeric plasmid. Our data show that mutations in the regions surrounding the ARS1 consensus sequence cause increases in the frequency of simple loss (1:0) events without affecting the rate of nondisjunction (2:0). Removal of the consensus sequence itself causes a drastic increase in the rate of simple loss. Sequences sensitive to mutagenesis were identified in each flanking region and differ with respect to their location and importance to ARS function. These results suggest that the role ARS1 plays in plasmid maintenance deals with the replication and/or localization of the plasmid in yeast. PMID- 3333307 TI - Physical separation and functional interaction of Kluyveromyces lactis and Saccharomyces cerevisiae ARS elements derived from killer plasmid DNA. AB - Two DNA fragments which have autonomously replicating sequence (ARS) activity in both Saccharomyces cerevisiae and Kluyveromyces lactis have been isolated from the K. lactis kl killer plasmid. One fragment (Kla1) is 700 base pairs (bp) in length and plasmids carrying it are mitotically unstable in both hosts. In K. lactis, this instability leads to colonies having a 'nibbled' phenotype when grown on selective media and appears to be the result of inefficient plasmid segregation. The other fragment (Kla2) is an artificial junction fragment of 1100 bp which was produced during the cloning procedure. Kla2 has been divided into two sub-fragments Kla2A and Kla2B which have, respectively, ARS activity in K. lactis and S. cerevisiae but not the other species. This indicates that these two closely related yeasts have different sequence requirements for ARS activity. Kla2B contains a perfect match to the S. cerevisiae ARS consensus but Kla2A does not. Both Kla2A and Kla1 share a 10 bp sequence as the sole region of homology between them. This sequence, 5'TCATAATATA3', is tentatively offered as defining the ARS consensus sequence for K. lactis. PMID- 3333308 TI - Orthogonal-field-alternation gel electrophoresis banding patterns of DNA from yeasts. AB - Chromosomal DNAs from various yeast species were separated by orthogonal-field alternation gel electrophoresis (OFAGE). To this end we developed a spheroplasting and lysis method to obtain intact DNA from both ascomycetous and basidiomycetous yeasts. The OFAGE banding patterns of 22 ascomycetous and four basidiomycetous yeast strains were compared. The strains represented species from the genera: Brettanomyces, Candida, Cryptococcus, Filobasidiella, Geotrichum, Hansenula, Kluyveromyces, Pachysolen, Pichia, Rhodosporidium, Rhodotorula, Saccharomyces, Saccharomycodes, Saccharomycopsis, Schizosaccharomyces and Zygosaccharomyces. Variations occurred in the number of bands and their positions in the gel, not only among strains of different genera but also among species from the same genus and even between varieties of the same species. The ascomycetous yeasts, with the exception of Saccharomyces cerevisiae, only showed one to five bands of DNA larger than 1000 kilobase pairs (kb) in general none smaller. The patterns of the four basidiomycetous yeasts revealed also a few large DNA bands but in addition one to six bands ranging in size from 500 to 1000 kb, with the exception of a single smaller chromosome in Rhodotorula mucilaginosa. From the OFAGE banding patterns of strains studied here it appears that in Sacch. cerevisiae the partitioning of DNA over chromosomes is unique. But rather than the large number of chromosomes, the presence of four chromosomes with less than 500 kb of DNA is characteristic for Sacch. cerevisiae. PMID- 3333309 TI - [Surgical treatment of endomyocardial fibrosis. A cooperative study]. PMID- 3333310 TI - [Surgical treatment of ulcerated lesions of the brachiocephalic trunk. Report of 2 cases]. PMID- 3333312 TI - [Pulmonary aneurysms]. PMID- 3333311 TI - [Cardiovascular uses of digital angiography]. PMID- 3333313 TI - [Chromosome anomalies and male infertility. A study of 1,444 subjects]. AB - Chromosomal anomaly was detected in 7.6% of a cytogenetic survey of 1,444 infertile male azoospermia or oligozoospermia with a sperm count below 20 million/ml. Anomalies are especially of the sex-chromosome and of autosomal robertsonian translocation type. Distribution of these subjects on account of the sperm count has pointed out an increase of chromosomal anomalies in inverse ratio to the sperm count. PMID- 3333314 TI - [Failure of human reproduction. The role of the HLA system]. PMID- 3333315 TI - [The karyotype of sterile and infertile men]. PMID- 3333316 TI - [Immunocytological distribution of HP1 group protamines in human testes and ejaculated spermatozoa]. AB - Specific antisera have been obtained against the purified human sperm protamine HP1b. The specificity of antibodies was assessed in dot-blot and western-blot assays. Antibodies showed high binding to protamine HP1 group. Nevertheless cross reactivity between HP1 and the other protamines (HP2 - HP3 - HP4) could not be excluded. Immunohistochemical studies revealed that protamines HP1 were detected in nuclei of ejaculated sperm after chromatin decondensation. In testis, they appeared in nuclei of elongating spermatids. PMID- 3333317 TI - [Immunologic abortion and its treatment]. PMID- 3333318 TI - New suggestions for the physiological role of secretory protein-I. AB - A major endocrine secretory protein of unknown function termed secretory protein I or, alternatively, chromogranin A, is attracting increasing attention. Because of its abundance and apparently universal presence in endocrine and neuroendocrine cells, many suggestions for a physiological role have been advanced. Recent data provide the first firm bases for some proposed functions that include a regulator of a novel protease capable of converting prohormones to hormones, a hormone precursor, and through its calcium-binding and aggregating properties, a secretory granule condensing protein. PMID- 3333319 TI - Heterogeneity of age-related fractures: implications for epidemiology. AB - Despite a general impression to the contrary, the risk factors for age-related fractures are poorly understood. There are indications, however, that these risk factors may vary from one skeletal site to another, depending on the pathophysiology of bone loss at the site and on the relative contributions of trauma and bone strength. Accurate knowledge of risk factors for specific fractures could help in the design of efficient screening and treatment programs for osteoporosis, while a clear understanding of fracture heterogeneity might lead to new hypotheses concerning etiology. However, a much more comprehensive approach to the study of the risk factors for age-related fractures will be necessary to achieve these ends. PMID- 3333320 TI - Developmental appearance of Gla proteins (osteocalcin) and alkaline phosphatase in tooth germs and bones of the rat. AB - The tissue distribution and developmental appearance of alkaline phosphatase and Gla proteins, relative to mineralization were examined. Undecalcified sections of tooth germs, calvaria and alveolar bone of the rat were immunostained for Gla proteins, (indirect immunofluorescence and avidin-biotin-peroxidase-complex) and then stained for alkaline phosphatase activity. In the growth regions of tooth germs, Gla protein was observed in young odontoblasts and in early predentin, at a stage prior to formation of the first mineralized dentin. Similar results were obtained for bone: young osteoblasts as well as osteoid were immunopositive for Gla protein prior to formation of the first mineralized bone. Histochemical staining revealed that differentiating odontoblasts and osteoblasts exhibited alkaline phosphatase activity at stages prior to appearance of Gla proteins and that cells adjacent to odontoblasts and osteoblasts (not directly involved in the formation of predentin/dentin and osteoid/bone) stained for alkaline phosphatase, but not for Gla proteins. We conclude, that in these bone- and dentin-forming cells, alkaline phosphatase activity is expressed before the appearance of Gla proteins, but that both appear before the onset of mineralization. We also conclude that Gla protein is a more specific marker for bone and dentin formation than histochemical alkaline phosphatase activity, since only the cells directly involved in these processes were immunostained for Gla protein. PMID- 3333321 TI - Organ specificity of islet cell surface antibodies (ICSA) in insulin-dependent diabetes mellitus. PMID- 3333322 TI - [Method for the reproduction of mandible--Part II]. PMID- 3333323 TI - [Study of endocrine-exocrine relationship in the pancreas. II. Measurement of some islet hormone-like substances in human pancreatic juice]. PMID- 3333324 TI - [Statistical review on surgeries with difficult intubation in the first Department of Oral Surgery, Josai Dental University Hospital]. PMID- 3333326 TI - Scoliosis: a review for the generalist. PMID- 3333325 TI - Studies on a clinical marker of diabetes mellitus: (3). Effects of calcium ions on insulin binding to human erythrocyte insulin receptors. PMID- 3333327 TI - Critical care as an integral part of trauma care. AB - There appears to be reasonable evidence to support the concept of trauma centers, as well as ICUs for the critical care management of the seriously injured trauma patient. For optimal care of such patients, there must be effective delivery of such critical care. Despite some concerns as to who should provide such care to trauma patients, as well as all other patients, there is little debate over the goal of such treatment--that is, optimal care of these seriously injured patients. With this goal in mind, each institution must design a system that provides this care. In most instances, this requires participation between trauma surgeons and critical care specialists, as well as trauma and critical care services. With proper leadership and systems to ensure effective communication between such services, these goals can be achieved. Important secondary goals, in education and research, can also be achieved by such methods. Rather than further fractionate the care of patients, who frequently need 24-hour physician coverage and involvement of people with many different specialty areas of knowledge, it is crucial that an effective, cooperative system be designed for each institution that provides this care. PMID- 3333328 TI - Initial management of the trauma patient. AB - The early management of the multiply injured patient is discussed. Emphasis is placed on recognizing life-threatening injuries early, intervening with appropriate treatments, performing a complete initial assessment, and establishing definitive care. Specific organ systems and injuries are stressed. PMID- 3333329 TI - Anesthesia for trauma. AB - This article presents basic anesthetic management problems and procedures together with newer anesthetic drugs and monitoring techniques that are likely to be encountered by intensive care physicians. The author's goal is to familiarize all critical care unit based members of the resuscitation team with current aspects of anesthetic management of the trauma patient. PMID- 3333330 TI - Management of spinal cord injury in the critical care setting. AB - Approximately 12,000 Americans suffer traumatic spinal cord injuries each year. This article discusses the management of their neurologic, respiratory, cardiovascular, gastroenterologic, and genitourinary complications in the critical care setting. PMID- 3333331 TI - Special problems in management of pediatric trauma. AB - Until recently, concern over the care of the trauma victim has largely involved the adult population; although 7% of emergency calls are for the pediatric patient, insufficient attention has been paid to the care of these children. This article concentrates on those unique problems encountered in the management of pediatric trauma in prehospital and hospital settings. PMID- 3333333 TI - Radiologic techniques in the treatment of the critically ill trauma patient. AB - Discussed in this article are portable chest x-ray for imaging abnormalities in pulmonary aeration, pleural disease, and the position of life-support apparatus and abdominal computed tomography and ultrasonography. PMID- 3333332 TI - Massive transfusion. AB - Massive transfusion is a potentially serious problem associated with a number of complications, including changes in coagulation factor and platelet concentration, nonmechanical bleeding, hypothermia, pulmonary dysfunction, hypokalemia and hyperkalemia, hypocalcemia, hypomagnesemia, acidosis and alkalosis, immune suppression, blood transfusion reactions, and transmission of infectious diseases. The pathophysiology and management of massive transfusion are reviewed in this article. PMID- 3333334 TI - Critical care complications in the trauma patient. AB - Critical care therapy of the multiply injured patient results in multiple potential complications. Nosocomial infections, gastrointestinal complications, and pulmonary complications are reviewed. Complications that are anticipated can often be avoided by prophylactic therapy. Early intervention, once complications have occurred, may result in decreased morbidity and mortality. PMID- 3333335 TI - The cardiopulmonary effects of sepsis on the trauma patient. AB - The cardiopulmonary effects of acute infection are inflammation-induced. Inflammatory mediators can both initiate and perpetuate the characteristic hyperdynamic, hypermetabolic state. PMID- 3333336 TI - Management of sepsis following injury. AB - Sepsis is a significant cause of late morbidity and mortality in the severely injured patient. In addition to the risk factors of shock, multiple transfusions, and contamination, the trauma patient may have the additional factor of severe immunologic depression. The prevention of sepsis should be an early consideration. Invasive diagnostic and therapeutic maneuvers should be limited to those that are absolutely necessary, since the incidence of nosocomial infection is high. Prophylactic antibiotics should not be misused, as these may increase the risk of serious, resistant infections. Frequent examination of sputum smears may allow the early diagnosis of pneumonia. Nutritional supplementation can improve host defenses, and should be instituted early. The patient in septic shock should be resuscitated and stabilized in the intensive care unit. Monitoring should include determination of cardiac index and systemic oxygen consumption. Computed tomography has emerged as the primary modality for the diagnosis of intra-abdominal sepsis. When combined with percutaneous drainage of abscesses, it represents a rapid and safe approach to the diagnosis and treatment of the critically ill septic patient. In certain cases, such as bowel perforation or necrosis, anastomotic breakdown, or acalculous cholecystitis, laparotomy is the procedure of choice. Opportunistic infections may become significant in patients who have required a prolonged course of treatment. In the patient with multiple organ-system failure who is not responding to therapy and in whom no clear source of sepsis has been identified, exploratory laparotomy should be considered. Antibiotics should be used with caution and should not started in every patient with a fever. Their use should be directed by appropriate cultures and sensitivities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333337 TI - Key factors that determine the clinical prognosis of dental implants. PMID- 3333338 TI - Luteinized unruptured follicle syndrome. PMID- 3333339 TI - Oral contraceptive-induced changes in plasma lipids: do they have any clinical relevance? AB - The plethora of published studies investigating oral contraceptive pill (OC) induced changes of various plasma lipids and their ratios together with repeated reviews of these studies in the literature, are all based on the assumption that OC-induced favourable or unfavourable lipid profiles decrease or increase a pill associated cardiovascular risk. Some authorities have been led to recommend choice of pill formulations based on such changes of plasma lipids. In a combined review of relevant cardiovascular and OC epidemiological studies no evidence is found for these assumptions and recommendations. There is no evidence of OC induced atherosclerotic disease, and pill-induced changes of plasma lipids within normal limits are therefore probably without any clinical relevance. Profound changes towards a so-called favourable plasma lipid profile may, on the contrary, be detrimental in terms of pill-associated cardiovascular events. PMID- 3333341 TI - Clinical trial that led to FDA approval of zidovudine is published. PMID- 3333340 TI - Recombinant DNA in filamentous fungi: progress and prospects. AB - Recombinant DNA technology enables the creation of well-defined alterations in the genetic material of an organism. Methods to manipulate recombinant DNA in the filamentous fungi (a group of microorganisms that includes species of academic as well as commercial interest) have recently been developed. This has been the result of adaptation of procedures successfully employed in the manipulation of other microorganisms. There are a number of similarities in the behavior of recombinant DNA in different fungi, but a number of differences have also been observed between the filamentous and the nonfilamentous fungi. Such differences include the ability to identify DNA replication origins and the host range of expression of fungal genes. PMID- 3333342 TI - Management of fibromyalgia, a distinct rheumatologic syndrome. AB - The pathophysiology and management of fibromyalgia, a unique nonarticular rheumatologic syndrome characterized by diffuse musculoskeletal aches and pains, stiffness, discrete tender points at typical soft-tissue sites, and a characteristic sleep disturbance, are reviewed. The prevalence and incidence of fibromyalgia are not known, but it is one of the most common conditions seen by rheumatologists (after degenerative joint disease and rheumatoid arthritis). It was previously thought to involve inflammation of fibrous intermuscular septa and is sometimes referred to in the literature as fibrositis. It is not primarily psychogenic, but psychological factors may contribute. The tender points are the key to diagnosis. Fibromyalgia may be classed as primary (when no underlying disease is present) or secondary (when an associated condition exists). The pathophysiology of fibromyalgia is unknown but appears to involve complex interactions of central neurotransmitters with a relationship to pain perception, mood, and sleep. Treatment is empiric; nondrug treatment involving education, relaxation, and increased physical activity is essential. Few controlled trials of drug therapy have been conducted. Analgesics, anti-inflammatory drugs, phenothiazines, tricyclic antidepressants, and the tricyclic muscle relaxant cyclobenzaprine have been used; low doses of amitriptyline or cyclobenzaprine provide increased control of pain and mood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333343 TI - The use of echocardiography in the diagnosis and follow-up of aortic valve endocarditis: a case report and literature review. PMID- 3333344 TI - Audit of ultrasound scanning: antenatal diagnosis of congenital abnormalities in Harare, Zimbabwe. PMID- 3333345 TI - In-vivo falciparum malaria response to chloroquine in Kisumu-Kenya. PMID- 3333346 TI - Efficacy of traditional chewing sticks in plaque control. PMID- 3333347 TI - Experimental evidence for the adaptive value of sexual reproduction. AB - It is generally believed that recombination by sexual reproduction is unfavourable in constant environments but is of adaptive value under changing environmental conditions. To test this theory, experimental populations of yeast (Saccharomyces cerevisiae) were set up and maintained at different levels of environmental heterogeneity. Recombination was estimated by determining sporulation rates. Sporulation rates first increased in populations living in highly variable environments, but after some time began to decrease. The decrease started last and was slowest in populations which were maintained under the same conditions for a sufficiently long time, to allow some adaptation of the gene pool to the respective environment. Patterns of genotypic variability could not be interpreted in such simple terms, but there was a statistically significant correlation between sporulation rate and genotypic variability. This correlation is to be expected because recombination generates genotypic variability. Summing up, recombination by sexual reproduction is advantageous in changing environments if the population can track the changes in the environment by changing its genotypic structure. PMID- 3333349 TI - Genetic research with nonhuman primates: serving the needs of mankind. Proceedings of an international symposium. San Antonio, Texas, March 2-5, 1986. PMID- 3333348 TI - Pleiotropic effects of environment-sensitive genes affecting fitness in relation to postmating reproductive isolation. AB - With regard to speciation in sexually reproducing organisms, some population geneticists continue to argue about the relative merits of sympatry versus allopatry. However, all workers seem quite comfortable with the conventional scenario depicting how reproductive isolation arises between subpopulations in the state of incipient speciation. This view according to which the evolution of reproductive isolation mainly results from some genetic divergence consecutive to a substantial restriction in gene flow is questioned here. A verbal model is described in which gene flow is no longer seen as being first interrupted by a mere physical barrier. The model is based on limited genetic changes at loci influencing fitness but it places two important constraints on the properties of the genetic elements involved in it. One of them is concerned with the environment-sensitivity of the mutations implicated in the process, and the other with their presumed pleiotropic action on a behavioural trait. PMID- 3333350 TI - Immunological and genetic factors influencing development and susceptibility to cancer. AB - The results of a variety of studies on the genetic and immunological aspects of reproduction can be integrated into a hypothesis about the factors that regulate implantation and development and that may also cause an increased susceptibility to cancer. The primary condition for successful reproduction is genetic compatibility between the mating partners: there must be no recessive lethal genes that could act alone or epistatically to cause embryonic or fetal death. Such recessive lethal genes have been identified in the mouse (t-haplotypes) and in the rat (grc), and there is some evidence that they also exist in humans. Immunological factors may modulate the implantation of the fertilized ovum under some circumstances after the genetic condition has been met. The same genetic factors that affect development may also affect susceptibility to cancer. This part of the hypothesis is supported by a number of clinical correlations between congenital defects and a higher incidence of cancer and by the demonstration of an increased susceptibility to the effects of chemical carcinogens in rats carrying the grc. PMID- 3333351 TI - Isozymes as bioprobes for genetic analysis of nonhuman primates. AB - The identification and the utilization of genetically determined electrophoretic differences of enzymes between the individuals of species as well as between cell lines have played an important role in the advancement of mammalian genetics during the past quarter of a century. In an explicit search we found a number of red cell enzyme polymorphisms in each of the following four species: chimpanzees, orang utans, rhesus monkeys and brown capuchins. Allelic distribution patterns among populations have indicated trends of subspeciation among chimpanzees and orang utans due to geographic barriers leading to reproductive isolation. Investigations of quantitative levels of red cell glucose-6-phosphate dehydrogenase have suggested that relative activity profiles of certain enzymes among species may be helpful in studies of the evolution of physiological traits and their biological significance during speciation. A large number of biochemical genetic markers in primate-rodent (i.e., chimpanzee-, gorilla-, orang utan-, rhesus monkey- and African green monkey-Chinese hamster) somatic cell hybrids have been identified and are useful for primate genetic analysis. Some of the biologically relevant observations on the enzyme markers in the above mentioned primate species are discussed. PMID- 3333352 TI - Chromosome phylogenies of man, great apes, and Old World monkeys. AB - The karyotypes of man and of the closely related Pongidae--chimpanzee, gorilla, and orangutan--differ by a small number of well known rearrangements, mainly pericentric inversions and one fusion which reduced the chromosome number from 48 in the Pongidae to 46 in man. Dutrillaux et al. (1973, 1975, 1979) reconstructed the chromosomal phylogeny of the entire primate order. More and more distantly related species were compared thus moving backward in evolution to the common ancestors of the Pongidae, of the Cercopithecoidae, the Catarrhini, the Platyrrhini, the Prosimians, and finally the common ancestor of all primates. Descending the pyramid it becomes possible to assign the rearrangements that occurred in each phylum, and the one that led to man in particular. The main conclusions are that this phylogeny is compatible with the occurrence during evolution of simple chromosome rearrangements--inversions, fusions, reciprocal translocation, acquisition or loss of heterochromatin--and that it is entirely consistent with the known primate phylogeny based on physical morphology and molecular evolution. If heterochromatin is not taken into account, man has in common with the other primates practically all of his chromosomal material as determined by chromosome banding. However, it is arranged differently, according to species, on account of chromosome rearrangements. This interpretation has been confirmed by comparative gene mapping, which established that the same chromosome segments, identified by banding, carry the same genes (Finaz et al., 1973; Human Gene Mapping 8, 1985). A remarkable observation made by Dutrillaux is that different primate phyla seem to have adopted different chromosome rearrangements in the course of evolution: inversions for the Pongidae, Robertsonian fusions for the lemurs, etc. This observation may raise many questions, among which is that of an organized evolution. Also, the breakpoints of chromosomal rearrangements observed during evolution, in human chromosomal diseases, and after ionizing irradiation do not seem to be distributed at random. Chromosomal rearrangements observed in evolution are known to be harmful in humans, leading to complete or partial sterility through abnormal offspring in the heterozygous state but not in the homozygous state. They then become a robust reproductive barrier capable of creating new species, far more powerful than gene mutations advocated by neo Darwinism. The homozygous state may be achieved especially through inbreeding, which must have played a major role during primate evolution.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3333353 TI - The major histocompatibility complex of primates. AB - The major histocompatibility complex (MHC) encodes cell surface glycoproteins that function in self-nonself recognition and in allograft rejection. Among primates, the MHC has been well defined only in the human; in the chimpanzee and in two species of macaque monkeys the MHC is less well characterized. Serologic, biochemical and genetic evidence indicates that the basic organization of the MHC linkage group has been phylogenetically conserved. However, the number of genes and their linear relationship on the chromosomes differ between species. Class I MHC loci encode molecules that are the most polymorphic genes known. These molecules are ubiquitous in their tissue distribution and typically are recognized together with nominal antigens by cytotoxic lymphocytes. Class II MHC loci constitute a smaller family of serotypes serving as restricting elements for regulatory T lymphocytes. The distribution of class II antigens is limited mainly to cell types serving immune functions, and their expression is subject to up and down modulation. Class III loci code for components C2, C4 and Factor B (Bf) of the complement system. Interspecies differences in the extent of polymorphism occur, but the significance of this finding in relation to fitness and natural selection is unclear. Detailed information on the structure and regulation of MHC gene expression will be required to understand fully the biologic role of the MHC and the evolutionary relationships between species. Meanwhile, MHC testing has numerous applications to biomedical research, especially in preclinical tissue and organ transplantation studies, the study of disease mechanisms, parentage determination and breeding colony management. In this review, the current status of MHC definition in nonhuman primates will be summarized. Special emphasis is placed on the CyLA system of M. fascicularis which is a major focus in our laboratory. A highly polymorphic cynomolgus MHC has been partially characterized and consists of at least 14 A locus, 11 B locus, 7 C locus class I allelic specificities, 9 Ia-like class II antigens and 6 Bf (class III) variants. PMID- 3333354 TI - Immunogenetic studies of maternal-fetal relationships: a review: why newborn rhesus monkeys don't get hemolytic disease. AB - The discovery of the Rh blood group factor in humans was made using the red blood cells of rhesus monkeys. Because of its importance to human medicine and immunogenetics, this finding contributed greatly to the appreciation of the importance of nonhuman primates in research. It is now widely recognized that blood group incompatibility between mother and fetus can lead to differential fertility, fetal death, and hemolytic disease of the newborn (HDN). The blood group systems of several nonhuman primate species have been studied in detail and found to be analogous, although not identical, to those of humans. It is therefore surprising that HDN has been reported in only four nonhuman primate species--marmosets, sacred baboons, chimpanzees, and orangutans. Maternal-fetal blood group incompatibility and its consequences have been extensively studied in rhesus monkeys, and these macaques may well be representative of many nonhuman primates. Rhesus monkeys exhibit all five of the conditions that lead to HDN in humans: (1) blood group incompatible matings; (2) transplacental hemorrhage; (3) maternal immunization to blood group alloantigens on fetal erythrocytes; (4) transplacental transfer of maternal antibodies; and (5) coating of the newborn's erythrocytes. Yet, newborns show no clinical or hematological evidence of HDN. We have shown that the rhesus alloantibodies engendered by transplacental immunization do not mediate immune elimination of the newborn's erythrocytes. Evaluation of the maternal antibodies demonstrated that they have low titers and low avidities and perhaps belong to IgG subclasses that do not bind effectively to receptors on phagocytic cells of the rhesus reticuloendothelial system. The newborn's genotype may also affect the expression of allogeneic blood group antigens and thereby help protect the newborn's cells from destruction. These factors together undoubtedly play a major role in the survival of the antibody coated newborn's RBC and are thus able to account for the absence of HDN in this species. PMID- 3333355 TI - Historical perspective of genetic research with nonhuman primates. AB - Genetics became firmly established as a scientific discipline early in the twentieth century, but major genetic research programs that involve nonhuman primates have been initiated only in the last two decades. Considerable activity in this area has been stimulated by the concurrent development of powerful techniques for detecting variability in chromosomes, proteins, and DNA; the establishment of pedigreed breeding colonies; and the recognition that nonhuman primates are ideally suited as models of human disease and social structure. The subdisciplines of cytogenetics, immunogenetics, and biochemical genetics have established a firm basis for biomedical and evolutionary research with nonhuman primates, and they will contribute greatly to future research initiatives. More recently, the advent of molecular genetics has enhanced the opportunities for research; and the exploration of nonhuman primates as potential models for genetically mediated diseases has been richly rewarded. We stand at the threshold of a new and exciting era in genetic research with nonhuman primates. The results of research programs already underway not only will provide more definitive answers about the origin of man, but also will play a critical role in solving the health-related problems of the present and of the future. PMID- 3333356 TI - Use of monoclonal antibodies in genetic research with nonhuman primates. AB - Monoclonal antibodies, because of their specificity and unlimited availability, have become one of the most powerful experimental tools available to the biological sciences. It is possible to make monoclonal antibodies that bind to determinants that are monomorphic in one or more species or to determinants that are polymorphic within a species. Few monoclonal antibodies have been made using immunogens derived from nonhuman primates. However, some monoclonal antibodies that recognize monotypic markers in humans can be used to detect polymorphic markers in nonhuman primates. Thus, the rapid development of monoclonal antibodies specific for human proteins significantly increases the potential number of immunogenetic markers useful for studying phylogenetic relationships and for identifying genetic polymorphisms among nonhuman primates. PMID- 3333358 TI - Anti-inflammatory activity of superoxide dismutases: inhibition of carrageenan induced edema in rats. AB - Eighteen different superoxide dismutases from procaryote, plant, fish, bird and mammalian species have been tested for anti-inflammatory activity in the rat paw pad carrageenan-induced inflammation model. Very large differences in activity are observed. Homologous rat Cu-SOD is not active and indeed shows slight pro inflammatory activity. The different SODs have different iso-electric values, different metals (Cu, Mn or Fe) at the active centre, different molecular weights and different circulation lifetimes. Biological activity is a function of amino acid sequence rather than of such secondary parameters. PMID- 3333357 TI - The evolution of nonhuman primate social behavior. AB - A review of the recent literature concerning evolutionary mechanisms and possible genetic contributions to social behavior reveals a concentration on function rather than mechanism. Although functional consequences may influence future genetic changes in a population, they do not necessarily reflect evolutionary history. More important, genes cannot code for functions. Only when the anatomical structures and behavioral patterns of individuals are described can we study genetic contributions to social organization. Discussions of function in the abstract, without specification of mechanism, do not fall within the realm of scientific testing. PMID- 3333359 TI - Molecular evolution of ets genes from avians to mammals and their cytogenetic localization to regions involved in leukemia. AB - The mammalian homologues of the ets-region from the transforming gene of avian erythroblastosis virus, E26, consists of two distinct domains located on different chromosomes. Using somatic cell hybrid panels, the mammalian homolog of the 5' v-ets-domain (ets-1) was mapped to chromosome 11 in man, to chromosome 9 in mouse, and to chromosome D1 in cat. The mammalian homolog of the 3' v-ets domain (ets-2) was similarly mapped to human chromosome 21, to mouse chromosome 16, and to feline chromosome C2. To better define the human proto-ets domains, the genomic DNA was molecularly cloned and sequences analyzed. The ets-related sequences of human DNA on chromosomes 11 and 21 were found to be discontiguous, unlike that of the chicken and avian E26 virus genome, except for a small overlap region. We conclude that the ets sequence shared by the virus, the chicken and man is likely to contain at least two dissociable functional domains, identifiable as ets-1 and ets-2. The human ets-1 locus is transcriptionally active and encodes a single mRNA of 6.8 kb, while the second locus, human ets-2 encodes three mRNAs of 4.7, 3.2 and 2.7 kb. By contrast, the chicken homolog, having a contiguous ets-1 and ets-2 sequence, is primarily expressed in normal chicken cells as a single 7.5 kb mRNA. Because chromosome translocations have been associated with different human disorders, we have used our human probes with two panels of rodent-human cell hybrids to study specific translocations occurring in acute myeloid leukemias (AML). The human ets-1 gene was found to translocate from chromosome 11 to 4 in t(4;11)(q21;q23) and the human ets-2 gene was found to translocate from chromosome 21 to 8 in t(8;21)(q22;q22). Both translocations were found associated with the altered expression of ets. PMID- 3333360 TI - Oncogenes: molecular probes for clinical application in malignant diseases. PMID- 3333362 TI - The myb oncogene. AB - The highly conserved, single copy c-myb gene has been independently transduced by two avian acute leukemia viruses, AMV and E26. This gene has also undergone insertional mutagenesis by non-acutely transforming murine leukemia viruses in a number of hematopoietic tumors. The common denominator of these retroviral activations of c-myb appears to be truncation of the normal coding region at either or both ends. The role of point mutations in myb-induced leukemogenesis is currently unknown. The products of the c-myb gene and its altered viral counterparts are nuclear proteins, a large fraction of which are associated with the nuclear matrix. In addition, the myb gene products have short half-lives and bind DNA in vitro. These features suggest that myb may act by regulating DNA replication or transcription. Consistent with this notion, the expression of c myb is cell cycle dependent in several cell types. However, the abundant expression of c-myb in the thymus is not similarly regulated and may serve a different function. The expression of c-myb appears not to be limited to hematopoietic tissues as previously thought and the nature of the hematopoietic specificity of transformation by v-myb is not currently understood. Nevertheless, hematopoietic growth factors and their receptors appear to play an important role in such transformation. Two new experimental systems for studying myb have recently been described. First, the discovery of a myb-related gene in Drosophila should allow the application of powerful classical and molecular genetic approaches. The functional similarity of this distantly related gene to the much more closely related avian and mammalian myb genes is unknown. Second, recent studies of murine myb in normal and abnormal hematopoiesis offers several advantages relative to the avian system, such as in-bred animal strains, a wealth of specific cell-surface markers, and cloned hematopoietic growth factor and receptor genes. Isolation or construction of an acutely transforming murine myb retrovirus may thus be very useful. Several obvious goals for future research will be to define the function of myb proteins within the nucleus, to understand the regulation of myb expression during the cell cycle, to establish which molecular alterations are essential for converting c-myb into a transforming gene, and the determine the role of myb in human malignancies. PMID- 3333363 TI - Structure and mechanism of activation of the myb oncogene. AB - The results summarized in this review show that the normal chicken myb gene codes for a protein of 77 kd which appears to play an important role in the control and/or differentiation of hematopoietic cells of myeloid and T lymphoid series. The activation of this gene has been observed in chicken and murine systems. In the avian system, this has been achieved by transduction of the myb oncogene into a retrovirus. Such a transduction resulted in the deletion of coding sequences from both the 5' and 3' ends of the gene. Initiation and terminator codons in helper viral sequences have been substituted for the analogous sequences in the proto-oncogene. Deletion of similar stretches of sequence in both the viruses suggested the possibility that these deletions may play an important role in the activation of this gene. The availability of the murine model system allowed us to examine this question further. In the ABPL tumor system, the activation of the myb locus occurred as a result of viral integration in a region immediately upstream to the v-myb related sequences. In NSF-60 cell line, the activation is due to the viral integration toward the 3' end of the gene. In both cases the viral integration results in the synthesis of aberrant mRNAs that have suffered deletions similar to those observed in the avian system. In all instances this results in the synthesis of truncated proteins which appear to mediate the transforming function. The availability of chicken and mouse c-myb cDNA clones makes it possible to test this hypothesis directly by construction of retroviruses containing various deletion mutations. PMID- 3333361 TI - Structure and function of p21 ras proteins. AB - Cancer is a malfunction of cellular growth control. The discovery of oncogenes, first in transforming retroviruses, and later in human and animal tumors, may have uncovered the key to understanding one of the most elusive subjects of basic cell biology, namely, the controlling mechanisms of cell growth. The ras gene family encodes a group of closely related 21,000 dalton (p21) proteins with special affinity for guanine nucleotides. Other cellular proteins with similar biochemical properties, collectively known as G-proteins, include the regulatory G proteins of adenylate cyclase, the alpha subunit of transducin of retina rod outer segments, the recently identified rho gene proteins, and perhaps also the elongation factors, EF-Tu and EF-G, of the protein synthesis system. These G proteins have roles in cellular signal transduction; by analogy p21 may have a similar cellular function in mediating the flow of growth control signals. Recent progress in the cloning and sequencing of these genes, overproduction of gene products in E. coli, protein engineering, detailed biochemical characterization, and the molecular structure determined by high resolution X-ray crystallography, have helped to elucidate in great detail the structure and function of p21 ras proteins. p21 appears to have a small membrane binding domain at the C-terminus, which contains a palmitylation site at cysteine-186, four amino acid residues from the end. Separated by a variable "hinge" region, most of the rest of ras amino acid sequences are highly conserved in nature. Four regions of extensive sequence homology among G-proteins constitute the GTP/GDP binding domain. In the crystal structure of EF-Tu, four peptide loops connecting beta sheets and alpha helices form the pocket for binding GDP. Studies using site-directed mutagenesis and immnochemical probes, indicate that the basic structure of the GDP binding site is conserved between p21 and EF-Tu. Furthermore, these studies also conclude that GTP binding is crucial for p21 ras cellular function. Although the precise target molecules for p21 are still unknown, the finding of the on/off switch function for ras genes have provided a better understanding of the mechanism of proto-oncogene activation, and may also provide further impetus to explore means of cancer intervention by interfering with the switch function. PMID- 3333364 TI - Mechanism of specific site location and DNA cleavage by EcoR I endonuclease. PMID- 3333365 TI - The EcoR V restriction endonuclease. AB - Type II restriction endonucleases have attracted attention for two main reasons: firstly, their many applications in the dissection of DNA and in the construction of novel DNA molecules; secondly, as systems for studying the interactions of proteins with specific DNA sequences. With respect to the latter, the EcoR I restriction endonuclease has been examined in greater depth than any other type II enzyme [1-3]. However, the EcoR I enzyme has a major disadvantage as a system for studying DNA-protein interactions: the protein has a remarkably low solubility. The solutions in which EcoR I shows maximal activity, and also affinity for its recognition site, are saturated at less than 0.5 microM of this protein [4]. Consequently, many techniques that have been developed to study protein-ligand interactions but which require high concentrations of the protein in solution, such as NMR spectroscopy, cannot be used on EcoR I. But this drawback does not apply to all type II restriction enzymes. A different enzyme, the EcoR V restriction endonuclease [5-7], has special advantages as a system for studying DNA-protein interactions. In particular, this is the only type II restriction enzyme (apart from EcoR I [3]) for which crystals of the protein have been reported [7]. PMID- 3333366 TI - The organization and control of expression of the Pst I restriction-modification system. PMID- 3333367 TI - The Pvu II restriction-modification system: cloning, characterization and use in revealing an E. coli barrier to certain methylases or methylated DNAs. PMID- 3333368 TI - [Microinvasive carcinoma of the uterine cervix: a retrospective study of 85 cases and a proposed diagnostic and therapeutic protocol]. PMID- 3333369 TI - [Monoclonal antibodies in gynecologic oncology. I. Diagnostic aspects]. PMID- 3333370 TI - [Monoclonal antibodies in gynecologic oncology. II. Prognostic and therapeutic aspects]. PMID- 3333371 TI - [Current aspects of hormone therapy of endometrial carcinoma]. PMID- 3333372 TI - [Principal prognostic factors to guide the follow-up of cancer patients]. PMID- 3333373 TI - [Prevalence and identification of species of black-pigmented Bacteroides isolated from periodontal disease sites in humans]. PMID- 3333374 TI - [Studies on mechanisms of coaggregation of Eikenella corrodens with oral bacteria using monoclonal antibodies against bacterial lectin]. PMID- 3333375 TI - [Phospholipid components in some subgingival bacteria which are related to periodontitis]. PMID- 3333376 TI - [Study on the new gingival attachment following flap surgery (Part 12) The effect of bone regeneration on the formation of new cementum]. PMID- 3333377 TI - [A case of dilantin hyperplasia associated with cerebral palsy]. PMID- 3333378 TI - [A clinical evaluation of porous hydroxyapatite granules implants in human periodontal osseous defects]. PMID- 3333380 TI - [Effects of irrigation of pockets on clinical symptoms and oral bacterial flora in patients with periodontal disease--with scaling and root planing]. PMID- 3333379 TI - [An experimental study using fibroblast cell culture concerning the effectiveness of scaling and root planing]. PMID- 3333381 TI - [Cell attachment and growth of the cultured cells to the periodontally involved root surface--correlation between the roughness of the surface and the rate of cultured epithelial cell growth]. PMID- 3333383 TI - [Effects of periodontal and orthodontic therapy on periodontal health--a longitudinal study of periodontal condition associated with periodontal initial therapy in adults]. PMID- 3333382 TI - [Antibiotic therapy in periodontal disease. 3. Studies on methods for topical application of minocycline]. PMID- 3333385 TI - [Subgingival ultrasonic debridement with newly designed probe-typed tip. I. Accessibility into the bottom of deep periodontal pocket]. PMID- 3333384 TI - [A study of ultrasonography applied to dental diagnosis--the possibility of examining gingival form]. PMID- 3333386 TI - [A study of dental stain removal (Part V)]. PMID- 3333387 TI - A procedure for handling microorganisms during preparation for electron microscopy. PMID- 3333388 TI - Compartment syndrome: a complication of use of the MAST suit. AB - A case of compartment syndrome following the use of a MAST suit is reported. The most significant factor in its development is prolonged application combined with severe hemodynamic compromise. Amputation was performed or death occurred in 50% of reported cases. Compartment pressure monitoring should be done in patients who require a MAST suit for more than 4 h. PMID- 3333389 TI - Experimental study on the relationship between the initiation period of occlusal function and the tissue response around aluminum oxide implant. PMID- 3333390 TI - Imaging evaluation of several diseases of the salivary glands and surrounding structures: a preliminary report on sialographic, computed tomographic, ultrasonographic, and scintigraphic findings. PMID- 3333391 TI - Dimensional stability of a commercially available clasp pattern used for cast clasps in partial dentures. PMID- 3333392 TI - Development of a rational fabricating system for cast clasps. PMID- 3333393 TI - Reinforcement of cold-cured acrylic resin denture-base with 4-META adhesive resin and Co-Cr alloy wrought wires. PMID- 3333394 TI - An expert system for designing removable partial denture--the role of data base. PMID- 3333395 TI - Effect of tannin-fluoride preparation on caries-reduction of overdenture abutment. PMID- 3333396 TI - Mechanical support for the failing heart. AB - The National Heart, Lung, and Blood Institute (NHLBI) has sponsored considerable research directed toward basic studies on the etiology of heart disease and atherosclerosis. While progress has been very encouraging there are still significant numbers of patients with end-stage heart disease. NHLBI initiated goal-oriented research activities on the artificial heart based upon the recommendation of the National Heart Advisory Council in 1964. The major goal of the Artificial Heart Program was to develop devices which could be effectively used to rehabilitate patients with end-stage heart disease. This paper will describe the evolution and specific program goals of the Artificial Heart Program and provide a description of the left ventricular assist system (LVAS) and total artificial heart (TAH) research efforts. Specific attention will be directed toward defining device requirements, descriptions of the blood pump and energy converter, control system operation and energy transmission methods. A summary of experimental results and current development status will also be provided. PMID- 3333397 TI - Restoring cardiac function: an emerging spectrum of therapeutic options. AB - A spectrum of techniques for restoring cardiac function is emerging. Among patients with global congestive heart failure (CHF), cardiac transplantation may help a small minority for whom allografts are available; the total artificial heart may eventually benefit a larger number. For patients with left-sided CHF, parallel-assist techniques maximally augment cardiac output. In-series techniques can help others without major arrhythmias and some residual cardiac output. As compared with parallel assist, in-series methods offer lesser hemodynamic augmentation but greater intrinsic reliability and the possibility of deactivation of support for hours or days without increased risk. Additional advantages include simplicity of management and documented long-term clinical efficacy. PMID- 3333399 TI - Controlled drug delivery: a critical review. PMID- 3333398 TI - Thermedics' approach to ventricular support systems. AB - Temporary and permanent ventricular assist systems, developed by Thermedics, Inc., are described, including rationale, design, operation and surgical applications. Clinical data are presented for pneumatically driven temporary left ventricular assist devices (LVAD). Usefulness of this device rests on the assumption that tissue of a weakened heart can recover if relieved for a time by an LVAD. The surgical implantation of an LVAD is reported in a case where the patient later received a heart transplant. The concept and technology of the subsystems of a permanent ventricular assist system (VAS), now ready for preclinical trials, are discussed. Design of a low-speed, torque-motor driven blood pump is described. Details are presented on transcutaneous energy transmission by means of a transformer, one of whose coils is embedded under the skin. Though less efficient than percutaneous transmission, the method eliminates infection risk. Special types of polyurethanes are analyzed in respect to their biocompatibility. It is concluded that flocking of the polyurethane surface allows the growth of a biological lining which is highly antithrombogenic. Sintered metal powders are found to be most efficient for fabrication of rigid pump components. A lenticular pump design is proposed to solve the problem of pressure differentials in the sealed device. Cardiac endocrine functions are cited in support of using assist devices that leave the heart in place. PMID- 3333401 TI - Spandra: a sustained release battlefield wound dressing. AB - In 1981, our laboratories developed a family of elastomers which could be cured by ultraviolet (UV) radiation. Curing by UV radiation was a significant advance in chemistry, since it allowed ultra-fast curing of elastomers in a matter of seconds, as compared to several hours at 110 degrees C for conventional heat curing. We applied for a patent based on this technology, and the patent was allowed in mid-1984 [29]. Based on this technology, Thermedics submitted a proposal to the US Army for the development of a sustained-release battlefield wound dressing containing antibiotics and coagulants. The drugs were evenly distributed in the oligomer matrix, and subsequently cured in seconds under UV illumination, without the use of heat, organic solvents or water. Because delicate drugs are not subjected to heat, organic solvents or water, the pharmacological activity of the drugs is insured. Therefore, theoretically any drug may be incorporated into our dressing. Sustained release dressings were first developed at Thermedics in 1983, spurred by a contract from the US Army Medical Research and Development Command. Under this contract, the Company developed a new type of wound dressing capable of accelerating the healing process, retarding infection, and minimizing pain. Based on our TECOFLEX materials technology, the dressing performs like temporary artificial skin. Its transmission properties for oxygen, carbon dioxide, and water vapor are similar to those of intact skin. Thus, while excluding bacteria from the wound site, the dressing maintains an optimal moist environment for the promotion of rapid healing. The new drawing shown in Figure 10 minimizes pain during healing by preventing dehydration and shrinkage in the wound. Patient comfort is also enhanced by the incorporation of a special fabric which imparts flex properties to the bandage that are almost identical to those of human skin, with greater stretch in one direction than in another. This also facilitates application to complex body contours by only one attendant, an important feature in both hospital and emergency situations. Materials currently in use in hospitals are difficult to handle, requiring two or three nurses to apply large dressings. Thermedics' military wound dressing not only has the significant advantage of ease of application, but this dressing can also be used for delivery of drugs to a specific site.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3333400 TI - Transdermal drug delivery systems. PMID- 3333402 TI - Modern biomaterials advance the ancient art of dentistry. PMID- 3333403 TI - Present uses of polymers in dentistry--an introduction. PMID- 3333404 TI - Clinical behavior of composite resins. AB - Since the original development by Bowen in the 60's, composite resins have evolved into a widely used and successful restorative material. Although they exhibit certain inadequacies as a dental restorative material, improvements constantly are being made. Due to the aesthetic nature of the material, coupled with its potential for mechanical and chemical bonding to tooth structure, composite resins will become more broadly used in the future. PMID- 3333405 TI - Dentin bonding agents--a perspective on research and clinical use. AB - The last several years have shown remarkable advances in the development of dentin bonding agents. Today, a majority of dentists routinely use dentin bonding agents in clinical practice. Yet, despite this widespread acceptance, these materials are still in their infancy and require improvements in their performance as well as an understanding of their adhesion mechanisms. Bond strengths to dentin are sufficient to prove useful but are less than needed for totally reliable results. Furthermore, problems related to polymerization shrinkage of composite restorative materials can compromise the bond to dentin resulting in decreased adhesion and marginal seal. Better materials are now being developed, but, in the meantime, limitations of the current materials should be understood and respected in clinical application. PMID- 3333406 TI - Biocompatible resins in dentistry. AB - The evolution of treatment for dental disease has been keyed to developments in technology. Once the diseased tooth structure was removed, various materials were then utilized to restore health and function to the tooth. A major consideration must be the biocompatibility of the restorative materials--both to the vital process of the tooth, as well as the oral cavity. It has been generally accepted that calcium hydroxide containing products are the materials of choice to be placed in direct contact with the pulp, prior to placement of these restorative materials. As the demands on restorative materials became more defined, the requirements of the base materials also became greater. Due to the numerous desirable features of polymeric resins, the search for a biocompatible resin base system incorporating calcium hydroxide was initiated. PRISMA VLC DYCAL represents the first dental use of biocompatible resin in direct contact with vital tissue. PMID- 3333407 TI - Fluoride-releasing acrylics. AB - There are numerous examples in dentistry where demineralization, or even frank caries, develops near or in association with restorative or prosthetic materials. Leaking cavity margins and demineralization under bite splints are two examples. A slow-release source of fluoride could help to prevent these problems and provide added protection throughout the mouth. For this purpose a family of fluoride-releasing resins has been developed for use in various adhesive applications, and also for preparing temporary crowns and removable acrylic devices. These materials contain fluoride ions held to covalently bound positive charge sites within the polymer network. Release is by a diffusion/exchange mechanism in which anions from oral fluids diffuse to the charge sites and exchange with fluoride. Fluoride then diffuses to the surface and is released into solution. This method of release allows for the retention of adequate physical properties and is capable of a linear release rate for terms ranging from days to years. PMID- 3333408 TI - Preliminary results of clinical renal allograft transplantation in the dog and cat. AB - Renal allograft transplantation was performed as treatment for terminal renal failure in six veterinary patients. Three patients failed to survive the postsurgical period, one patient died due to acute allograft rejection, one patient died subsequent to complications of previous parenteral hyperalimentation and infection, and one patient was euthanatized due to the inability of the clients to maintain the effort necessary to manage a transplant recipient. Further clinical studies are necessary to determine if renal transplantation with cyclosporine (cyclosporin A)/prednisolone immunosuppression has the potential to provide practical treatment of terminal renal disease in clinical veterinary medicine. Pharmacologic and immunologic monitoring of transplant recipients with individualized immunosuppression is imperative. Careful surveillance is necessary to identify and eliminate nosocomial sources of infection. Candidates for transplantation cannot be critically ill or malnourished prior to surgery, and pet owners must be prepared for the financial and time commitments associated with caring for a renal allograft recipient. PMID- 3333409 TI - Efficacy of azathioprine versus cyclosporine on kidney graft survival in transfused and nontransfused unmatched mongrel dogs. AB - Sixteen mongrel dogs had bilateral nephrectomy and received a renal allograft from an unmatched mongrel. One group of eight dogs was treated orally with azathioprine and prednisone; another group of eight dogs was treated orally with cyclosporine and prednisone. Four dogs of each group received four blood transfusions each prior to surgery. Mean survival time was nearly the same in the azathioprine-treated and the cyclosporine-treated dogs. Transfusions prolonged survival in the azathioprine-treated group but not in the cyclosporine-treated group. Retrospective measurement of whole blood trough cyclosporine concentrations indicated marked variation between dogs and in the same dog at different times. This variation may have influenced graft survival. Only one dog survived the 9-month period of observation, indicating that refinements of the techniques used in this study will be required for long-term survival of renal allografts in unrelated mongrel dogs. PMID- 3333410 TI - Whole-body hyperthermia. Rationale and potential use for cancer treatment. AB - Whole-body hyperthermia is the controlled elevation of systemic temperature for therapeutic purposes. Historically, this treatment has been used for symptomatic control of many diseases. Recently, the potential therapeutic benefit of whole body hyperthermia in the management of neoplastic disease has been investigated vigorously. The rationale for improved tumor control is based on heat-induced enhancement of the antineoplastic effects of radiation and chemotherapy. Although the complex biologic interaction of heat and radiation has been studied for many years, chemotherapy combined with hyperthermia has been studied less thoroughly. Despite a lack of adequate long-term laboratory and clinical investigation, use of whole-body hyperthermia with chemotherapy and radiotherapy is a logical and potentially powerful therapeutic strategy for neoplasia. Relevant issues regarding the application of whole-body hyperthermia with more traditional modes of therapy are being studied in preliminary clinical trials involving dogs and humans. Identification of optimal timing and sequencing of adjunctive therapy, proper cytotoxic drug application, methods to further minimize toxicity, and heat sensitive tumor types will lead to expanded clinical use of whole-body hyperthermia. The historical development, clinical rationale, and application of whole-body hyperthermia for the control of disseminated or refractory neoplasia in humans and dogs is reviewed. PMID- 3333411 TI - Cutaneous sensory testing in the dog. PMID- 3333412 TI - Comparison of virulence factors and antibiotic resistance profiles of Escherichia coli strains from humans and dogs with urinary tract infections. AB - The purpose of this study was to compare virulence factors and antibiotic resistance profiles of Escherichia coli strains isolated from dogs and humans with urinary tract infections. Factors studied included resistance to antibiotics and the transferability of R-plasmids to a recipient E. coli; production of colicins, hemolysins, beta-lactamase, and urease; hemagglutination of erythrocytes; and fermentation of dulcitol. The canine E. coli isolates had a wider range of antibiotic resistance and a higher R-plasmid transmissibility rate. A higher percentage of the canine isolates produced colicins (40% vs. 24%), hemolysins (44% vs. 16%), beta-lactamase (52% vs. 4%), and fermented dulcitol (84% vs. 80%) as compared with the human isolates. The human isolates had a greater ability to hemagglutinate erythrocytes as compared with the canine isolates (24% vs. 8%). None of the isolates produced urease. PMID- 3333414 TI - Biochemical development of the lung and regulation of surfactant secretion. PMID- 3333413 TI - Cardiac contractility. A review. PMID- 3333415 TI - Glucocorticoid regulation of lung maturation. AB - The timing of fetal lung maturation is influenced by endogenous corticosteroids and is accelerated by glucocorticoid treatment. Other hormones have permissive or synergistic effects with glucocorticoids (e.g., thyroid hormones and activators of adenylate cyclase), indicating that lung development is under multi-hormonal regulation. Glucocorticoids affect both lung structure and differentiation of the surfactant system through actions in mesenchymal and epithelial cells. These effects are mediated through glucocorticoid receptors and involve gene activation with de novo synthesis of proteins. The number of inducible (for repressible) proteins is limited to -2% of total proteins, consistent with glucocorticoid effects on specific genes. Although some glucocorticoid-responsive proteins are known (enzymes of phospholipid synthesis and the antioxidant system; surfactant associated protein), the identity of function of most target proteins awaits further research. PMID- 3333416 TI - Introduction to molecular biology. PMID- 3333418 TI - Questions about surfactant for respiratory distress syndrome (RDS). PMID- 3333417 TI - Lung cell differentiation. PMID- 3333419 TI - Cellular metabolism of pulmonary surfactant. PMID- 3333420 TI - Lung injury and pulmonary edema in respiratory distress syndrome. PMID- 3333421 TI - Mercury resistant Escherichia coli in the sediments of a dental hospital. PMID- 3333422 TI - [Dental application of X-ray subtraction technique--extraction of salivary gland image]. PMID- 3333424 TI - [Clinical research on the processing of cold-curing resin--changes in height of the denture and variations on the mucosa surface]. PMID- 3333423 TI - [Examination of ultrasonographic image in oral cavity (quantitative estimation with two-value processing)]. PMID- 3333425 TI - [The dynamics in development of experimental gingivitis and in preformed cavities in rats]. PMID- 3333426 TI - [Studies on the masticatory efficiency-through masticatory efficiency measuring device by light blocking method]. PMID- 3333427 TI - [Application of the polyaramide fiber to denture base (Part 1)--Study on the reinforcement-effect of the polyaramide fiber to P.M.M.A. resin]. PMID- 3333428 TI - [A new measuring system using strain gauge for tooth mobilities under functions]. PMID- 3333429 TI - [Oral cytology; odontogenic myxoma]. PMID- 3333431 TI - [Assessment of the carcinogenic hazard of 6 substances used in dental practices. (II) Morphological transformation, DNA damage and sister chromatid exchanges in cultured Syrian hamster embryo cells induced by formocresol, iodoform, zinc oxide, chloroform, chloramphenicol and tetracycline hydrochloride]. PMID- 3333432 TI - Fumes from the spleen. PMID- 3333430 TI - Aneurysmal subarachnoid hemorrhage: prevention of delayed ischemic dysfunction with intravenous nimodipine. PMID- 3333433 TI - Follow-up of the first national birth cohort: findings from the Medical Research Council National Survey of Health and Development. AB - The medical work of a 40 year birth cohort study is described in order to show the continuing associations of childhood factors with later life health, behaviour, illness and survival. Comparisons with the health of children born at later times show the importance of a sensitive monitoring of changes in child health. A summary of work on social and psychological topics is also given, together with a complete list of publications from the study. PMID- 3333434 TI - The fluoride story. PMID- 3333435 TI - Ultrasonography in obstetrics. PMID- 3333436 TI - HIV infection in children: sizing up the paediatric problem. AB - Cases of paediatric AIDS have increased each year in the USA, as the disease has spread to the heterosexual community. In the USA the geographic distribution of perinatal AIDS cases mirrors the distribution of cases in women. To date, 503 HIV antibody positive women have been reported in the UK. It is likely that the increasing number of seropositive women will be reflected in an increase in the number of reports of perinatal HIV infection and AIDS. Although screening of blood donors and blood products has stopped further increase in infections from this route, as transfusion-infected children become symptomatic the burden on paediatric services will increase. PMID- 3333437 TI - Acid etch bridge: one year clinical evaluation. PMID- 3333438 TI - Is dental caries prevalence on the increase in Tanzania? PMID- 3333439 TI - [TEM observation of demineralized dentin surface for adhesion--comparison of etching agents]. PMID- 3333440 TI - [B-lactam antibiotics: grouping according to their chemical structure and bacteriological properties]. PMID- 3333441 TI - [Calcitonin in acute pain due to vertebral fracture in osteoporosis. Cooperative study]. PMID- 3333443 TI - [The development of computerization and our medicine]. PMID- 3333442 TI - [Gentamicin-tinidazole and gentamicin-clindamycin in severe bacterial infections: comparative study]. PMID- 3333444 TI - [Homeostatic mechanisms in physiology and pathology]. PMID- 3333446 TI - [A new building for the Sociedad Medica de Santiago]. PMID- 3333445 TI - [Low-dose clonidine in moderate arterial hypertension]. PMID- 3333447 TI - [Active rheumatic disease: changes in its epidemiology]. PMID- 3333448 TI - [Possibilities of removal of wax latent elasticity]. PMID- 3333449 TI - [Guiding plane in the reciprocity of hook and retention]. PMID- 3333450 TI - [Dependence of partial prosthesis retention on the direction of its installation]. PMID- 3333451 TI - [Metamorphosis in amphibians]. PMID- 3333452 TI - [An ex situ study of the adaptation of composite resin restoration to the cavity wall and the degradation of the restorative material in human primary molars]. PMID- 3333453 TI - The thirteenth International Conference on Yeast Genetics and Molecular Biology. Banff, Alberta, Canada, 31 August-5 September 1986. Abstracts. PMID- 3333454 TI - Misconceptions about the energy metabolism of Saccharomyces cerevisiae. PMID- 3333455 TI - Sequences important for gene expression in filamentous fungi. PMID- 3333456 TI - New combined method of specific and non-specific immunotherapy in grass pollen allergy. Theoretical and practical considerations. PMID- 3333457 TI - A simple and reliable method for visualization of the arterial autonomic nerve plexus by scanning electron microscopy. AB - A simple and reproducible procedure is described by which the autonomic nerve plexus in rat mesenteric arteries is revealed at a three-dimensional level, using scanning electron microscopy after HC1-hydrolysis. PMID- 3333458 TI - Immunohistochemical and immunoblot analyses of collagens in the developing fibrocartilage in the glans penis of the rat. AB - The distal segment of the os penis of rats is a fibrocartilage whose development is dependent on androgens. Electrophoretic and immunoblot analysis indicated that the fibrocartilage contained both type I and type II collagens. Immunohistochemically, type I collagen was detected in the fibrous matrix of the distal segment in all the stages examined. Type II collagen was detected first at 4 weeks in the extracellular matrix surrounding the mature chondrocytes distributed sparsely as single cells or small clusters among immature chondroblasts. The clusters reactive with anti-type II collagen serum increased in size and number at 6 weeks, and almost all the region of the distal segment became reactive with anti-type II collagen serum at 8 weeks. PMID- 3333460 TI - Occupational trauma for the dentist. PMID- 3333459 TI - [Masticatory forces and oral status]. PMID- 3333461 TI - Conservative restorative treatment following trauma. PMID- 3333462 TI - Selected aspects of posterior composite restorations. PMID- 3333463 TI - Cleft lip and palate. The state of the art. PMID- 3333464 TI - Psychosocial aspects of the treatment of facial deformity. PMID- 3333465 TI - Dental management of the traumatized child patient. PMID- 3333466 TI - [Antiplaque agents]. PMID- 3333467 TI - In pursuit of excellence. PMID- 3333468 TI - New approaches to the Begg technique. Part I--Qualitative aspects. PMID- 3333469 TI - A re-assessment of serial extraction. PMID- 3333470 TI - Cell migrations during morphogenesis: some clues from the slug of Dictyostelium discoideum. PMID- 3333471 TI - Models for MHC-restricted T-cell antigen recognition. PMID- 3333472 TI - Molecular biology of T-cell-derived lymphokines: a model system for proliferation and differentiation of hemopoietic cells. PMID- 3333473 TI - Specific inductive flypaper. PMID- 3333474 TI - Professor Franciszek Blawat, M.D. (1911-1987). PMID- 3333476 TI - History of the ophthalmological investigations in decompression sickness. PMID- 3333478 TI - The centenary of the Sri Lanka Medical Association. PMID- 3333477 TI - Herpes gestationis. PMID- 3333479 TI - [Indications for osteosynthesis of facial bones with miniaturized plates]. PMID- 3333475 TI - Characteristics of lactose-fermenting Salmonella strains from Poland. AB - In this study 184 lactose-fermenting Salmonella strains, collected in the National Salmonella Centre from the northern and central parts of Ponad were examined. Epidemiological, serological and biochemical investigations were carried out. Apart from this, chemotherapeutic resistance and male-phage sensitivity were determined. Most of strains belonged to S. agona serotype (S. typhimurium and S. oranienburg were also presented) which apart from the lactose fermenting ability retained all the remaining biochemical features typical of Salmonella bacilli, were male-phage M13 resistant and showed a high resistance to a wide spectrum of chemotherapeutics. In order to establish the way of the acquiring lac+ property by Salmonella bacilli P22 phage transduction and conjugation experiments, with E. coli F'lac and Hfr H as donors, were performed. S. agona lac- strains were shown to acquire the lactose-fermenting ability by mating with E. coli. PMID- 3333480 TI - [Osseous transplantation preceded by occlusion regulation in children with clefts of primary and secondary palate]. PMID- 3333481 TI - [The condition of marginal periodontium in pregnant women]. PMID- 3333482 TI - [Etching of enamel in literature survey]. PMID- 3333483 TI - [Conditions of work and health of stomatologists]. PMID- 3333484 TI - [Eightieth birthday of Professor Janusz Krzyzywicki, M.D. from the Medical Academy in Warsaw]. PMID- 3333485 TI - [Heliosit requires a base]. PMID- 3333486 TI - [Cytological assessment of the oral cavity in workers exposed to harmful factors at working site]. PMID- 3333487 TI - [Insulin secretion in acromegaly and Cushing's syndrome]. PMID- 3333488 TI - Hybridoma cultivation in defined serum-free media: growth-supporting substances. II. Insulin, other hormones, and growth factors. AB - The effects of insulin and hydrocortisone on growth of hybridomas in serum-free medium were studied. The optimum growth-stimulating concentration of insulin was 10 micrograms/ml. Omission of insulin resulted in substantially decreased growth (23-53% of the cells growing 3 days with insulin). The optimum growth-supporting concentration of hydrocortisone was 2 ng/ml. Hybridoma cells growing 3 days without hydrocortisone represented about 80% of the cells growing with hydrocortisone. Hormones testosterone, triiodothyronine, and prostaglandin F2 alpha as well as growth factors EGF and FGF had no growth-supporting effect. PMID- 3333490 TI - Polyploidization of the BTC-32 cell line from Triatoma infestans (Hemiptera, Reduviidae). AB - The cytophotometric evaluation of the Feulgen-DNA content of the BTC-32 cells at passage 160 after 6 days of growth demonstrated that polyploidy is relatively frequent in this cell line. 4C values were assumed to pertain to diploid nuclei at the S or G2 phases but also to polyploid nuclei at the G1 phase. Polyploidy in 4C nuclei is assumed to be attained by endomitosis. However, there are morphological indications that polyploidization in cells with an 8C-128C Feulgen DNA content could result from cellular and nuclear fusions, possibly mediated by viral particles present in the cell culture. Micronucleation was also frequent; it was assumed to be promoted by viral action or deficiency in some culture medium nutrient. These nuclear characteristics should be considered when using the BTC-32 cell line for monitoring the action of infective agents or their products. PMID- 3333489 TI - An enzyme-linked immunosorbent assay for detecting the chicken B cells. AB - Two modifications of an indirect enzyme immunoassay described here allow the discernment of chicken B and T cells when a polyclonal rabbit anti-chicken Ig antibody or a monoclonal antibody reactive with chicken IgM and IgG heavy chains is used. Comparison of both types of antibody in ELISA and in indirect immunofluorescence suggests that they can readily be exploited for detection of lymphoid cells with surface immunoglobulin markers. PMID- 3333492 TI - Keynote lecture. Etiologic insights from cancer mapping. AB - In the 1970s the epidemiology program at the U.S. National Cancer Institute made a systematic effort to identify cancer clustering by analyzing patterns of mortality at the county level, where the population is small enough to be relatively homogeneous, yet large enough to provide reliable data and stable rates. When the mortality rates for the period 1950-69 were plotted in a series of computer-generated color-coded maps, there arose a surprising number and variety of geographic patterns. This review describes how leads to the causes of several cancers have been generated and explored through a progression of descriptive and correlational studies, followed by analytical studies to determine reasons for the elevated risks in certain areas of the country. For example, the high lung cancer rates among men in some coastal areas were related mainly to asbestos exposures in shipyard work, while the elevated oral cancer rates among women in the rural south were linked to the use of smokeless tobacco (snuff). A recent update of cancer maps covering the period 1970-80 revealed geographic patterns resembling those in the earlier atlas, but with a tendency toward greater uniformity of rates around the country. Yet some new high-risk areas emerged, such as elevated rates of lung and oral cancers among women in Florida and along the Pacific coast, which seemed correlated with smoking habits, and high rates of non-Hodgkin's lymphoma among men in central areas that may be associated with agricultural exposure to herbicides. Our experience suggests that cancer mapping on a small-area scale is a useful strategy for formulating and pursuing leads to environmental and lifestyle determinants of cancer. In other countries also, the mapping approach has helped to stimulate and target research into the origins of cancer and the means of prevention. PMID- 3333493 TI - HTLV-I-associated myelopathy: an overview. AB - From our past clinical observations, we have identified a cluster of cases with distinct neurological manifestations and, together with our viral studies, it has been proven that in fact these cases belong to a new clinical entity. The association of this slowly progressive spastic paraparesis with human T-cell lymphotropic virus type I (HTLV-I) enabled us to designate this clinical entity as HTLV-I-associated myelopathy or HAM. Later studies showed that 1) the geographical distribution of HAM follows that of adult T-cell leukemia (ATL) and 2) viruses detected in both disorders were identical by DNA blotting assay, but HAM and ATL are definitely expressed clinically as distinct from the other. In this regard, human leukocyte antigen (HLA) studies and the pattern of immune responsiveness seem to show a clear segregation of one from the other. As many initially studied cases have responded favorably to corticosteroids and had frequent perivascular cuffing in the spinal cord of a necropsied case, it is likely that, in part, immune events play a role in the pathogenesis. Our efforts are now directed to determining whether a) HAM is purely an autoimmune process, or b) a slow virus infection with a long incubation period may be the culprit. PMID- 3333491 TI - Genetic linkage in the Norway rat. AB - The present status of research on genetic linkage is reviewed. Where possible, the data are statistically combined to give consolidated estimates of the recombination value. Ten groups of linked genes have been determined. The first assignments of linkage groups to specific chromosomes have been facilitated by inter-species cell hybridisation. PMID- 3333494 TI - Chromosomes and cancer families. AB - At the beginning of this century Theodor Boveri predicted that specific chromosome changes would be found to have a causal role in neoplasia. We are now beginning to acquire the evidence to substantiate this hypothesis. The evidence comes from two particular sources, (i) genetic environmental interactions and (ii) specific constitutional chromosome aberrations. Cancer incidence varies throughout the world. This is often due to the interaction of an environmental agent with a genetically varied population. Using UV and ionising radiation as examples it is argued that some individuals are more susceptible to genetic damage by these agents. Moreover, the genetic lesions which are caused by these agents are now being shown to be relevant to cancer. In the radiosensitive syndrome ataxia-telangiectasia for example, specific chromosome rearrangements have been defined which seem likely to be directly involved in the development of leukaemia in these patients. The second line of evidence comes from the study of patients who have constitutional chromosome abnormalities associated with susceptibility to specific cancers. It has now been shown that these chromosome changes mark the location of genes which are involved in the development of cancer and that these same loci are also important in the non-familial forms of these diseases. Thus we are beginning to understand for the first time the mechanistic pathway that leads from environmental agents, through chromosome damage, to the alteration of specific genes which control the neoplastic process. PMID- 3333495 TI - Keynote lecture. The familial syndrome of sarcomas and other neoplasms. AB - Observation of one kindred with sarcoma, breast cancer and other neoplasms has led to the recognition of a familial cancer syndrome in young patients. To date, 24 affected families have been enrolled in the Cancer Family Registry of the National Cancer Institute, and 21 others have been reported in the literature. The major feature of the syndrome is an autosomal dominant pattern of breast cancers and sarcomas of bone and soft tissue at unusually early ages. Additional components of the syndrome appear to be brain tumors, leukemia, and adrenocortical carcinoma in children and adolescents. Family members are prone to develop multiple primary cancer. In addition to descriptive reports, the syndrome has been detected in segregation analysis of a consecutive series of children with soft tissue sarcomas; in studies of breast cancer among mothers of unselected children with sarcomas; and in prospective observation for new cancers in our previously reported families. Laboratory studies are in progress to seek the gene(s) associated with this syndrome of diverse cancers. Studies of this rare disorder may provide new insights into the pathogenesis of the 5 component tumors, particularly breast cancer, the commonest cancer among women in the United States and elsewhere. PMID- 3333496 TI - Investigation of cancer case clusters: possibilities and limitations. AB - Discovery of meaningful biologic events through investigation of individual cancer case clusters is limited by the greater likelihood that any given cluster, otherwise unspecified, will be a random event and by restrictions arising from the necessarily retrospective nature of any studies undertaken. In the face of long and variable latencies, it is difficult to document potential oncogenic exposures and to estimate dosage. Since case numbers are usually small, statistical assessments may have only limited value. This, however, encourages greater attention to be given to case features and clinical details from which patterns of case associations within clusters can occasionally be seen. When similar epidemiologic case patterns are repeatedly encountered in different cluster situations (as was apparent with parish and school associations, reviewed here, in several communities in the United States), some biologic basis for such case clustering may be suspected. Similar suspicions are aroused when additional cases of rare cancer are observed in community settings to which case clustering has already drawn attention. PMID- 3333497 TI - Strategies to control cancer through genetics. AB - Although genetic factors may be essential in only a fraction of common cancers, it is important to identify individuals who merit genetic evaluation. The occurrence of cancer in an individual under one of the following circumstances may indicate an increased susceptibility to malignancy as a result of predisposing factors: cancer in both of paired organs, thought not to be the result of metastasis; more than one focus of cancer in a single organ (multifocal tumors); histologically similar malignant neoplasms in different parts of the same organ system; two histologically distinct cancers (multiple primary malignancies); cancer at an atypical age; at an atypical site; in the usually less often affected sex; associated with birth defects; associated with precursor lesions; in a person with immunodeficiency; or in a patient with one of the 200 Mendelian disorders where cancer is part of the clinical picture or a frequent complication. At risk are first-degree relatives of people who meet any of the above criteria. Also, a person should be considered at risk if two first-degree relatives had any form of cancer. A strategy to control cancers utilizing genetic knowledge should include such measures as: genetic counseling of individuals at risk for specific cancers because of a congenital or genetic disease in themselves or their relatives, or because of the pattern of cancer occurrence in the family; prenatal diagnosis for families with genetic conditions that predispose to cancer and are amenable to prenatal testing; surveillance of high risk individuals to detect early manifestations of new or recurrent disease; prophylactic removal of the target organ or tissue in appropriate cases; limiting exposure of high-risk individuals to known carcinogens or supplementing diets of high-risk individuals with anticarcinogens; and educational and administrative measures to promote practical application of genetic knowledge and to increase awareness of genetic factors in the etiology of cancer. Far from all individuals who are exposed to carcinogenic factors contract cancer, and in another common disease, atherosclerosis, it is well known that there is genetically determined variation in response to environmental or lifestyle factors that can cause disease. The emerging fields of human ecogenetics and predictive testing together with research progress in medical and molecular genetics are likely to improve greatly the possibilities for utilizing genetic knowledge to control cancer. PMID- 3333498 TI - Nakahara memorial lecture. Rare events and cancer epidemiology. AB - Physicians who think epidemiologically are rare. A method is suggested for detecting their aptitude early in their career when help may be offered to make the most of their special talent. Clusters geographically or in families may provide clues to cancer etiology. Clusters have been systematically thought by mapping cancer mortality in the US and independently in China. Case-control studies have revealed environmental exposure responsible for some of the clusters. Clusters noted by alert clinicians or other astute observers have revealed most of the known environmental causes of human cancers. Genetic influence in carcinogenesis has been identified by studies of peculiar cancer occurrence, such as familial aggregation, multiple primary cancer or the occurrence of cancer with other diseases as, for example, congenital malformations and immunodeficiency disorders. Ethnic differences in cancer occurrence may be revealing. Thus, in Japan there is low frequency of B-cell lymphoma but high frequency of certain autoimmune diseases, as if inherent protection against one predisposes the other. As a rule of thumb, the occurrence of three rare observations is not likely to be due to chance. Examples include ideal carcinoma in three persons with cystic fibrosis of the pancreas who survived to about 30 years of age, and the occurrence in Klinefelter's syndrome of germ cell tumor of the pineal--a neoplasm that has an unusually high frequency in Japan. Finally, the history of discoveries concerning cancer etiology, an aspect of what Comroe has called "research on research", can point the way to new discoveries in the future. PMID- 3333499 TI - Development of adenocarcinoma and acquired cystic disease of the kidney in hemodialysis patients. AB - Ninety-six hemodialysis patients were examined using computed tomography (CT) scan. Multiple cysts were found in 43.5% of those on hemodialysis for less than 3 years and in 79.3% of those who had been on dialysis for more than 3 years. Four patients had adenocarcinoma of the kidney; all 4 were in their 3rd and 4th decade and had been on hemodialysis for more than 5 years. Histologically, renal cell carcinomas were clear cell, or clear and granular cell carcinomas. All cancer patients had acquired cysts, intracystic epithelial hyperplasia (atypical cysts) and cysts or solid adenoma in the same kidney. Such findings are similar to those of experimental cancer of the kidney with respect to multifocal and bilateral lesions. Of the 1,103 total reported dialysis patients in Japan and abroad, 47.1% had acquired cystic disease and 1.5% renal cell cancer. In a nationwide survey, a total of 119 patients (96 males and 23 females) with adenocarcinomas were found. Their mean age was 49.5 +/- 12.1 years. The mean duration of dialysis was 70.8 +/ 44.4 months. Twenty-five of them had metastases. Since the total number of hemodialysis patients in Japan is 66,310 (December, 1985), many adenocarcinomas may not have been discovered. Acquired cystic disease regresses rapidly after successful renal transplantation. This lends credence to the uremic metabolite accumulation hypothesis to explain the development of acquired cysts and tumors of the kidney in dialysis patients. In conclusion, renal cell carcinoma in dialysis patients is closely related to the acquired cystic disease of the kidney. The frequency of renal cell cancer in long-term dialysis patients is increasing because of the higher incidence of acquired cysts with longer dialysis administration. PMID- 3333501 TI - [Coordination with upper and lower dental arch widths for the sagittal osteotomy of the mandibular ramus. Preoperative orthodontic treatment with expansion screw and corticotomy]. PMID- 3333500 TI - Environment and malignancies of the lymphatic system. AB - The possible effects of environmental factors on childhood lymphatic leukemia and intestinal lymphoma are reviewed. It is suggested that the subtype of childhood acute leukemia is determined by a spontaneous mutation in the proliferating lymphoid pool. The latter is affected by environmental factors such as the type of infections in the pediatric population. The changing leukemia subtype pattern in the Gaza Strip and the fact that intestinal lymphoma with malabsorption has practically disappeared from Israel strongly suggest that environmental factors do play a role in lymphatic malignancies. PMID- 3333502 TI - [Development of functional examination system of pronunciation by dento palatography and analyses of articulatory movements and speech sounds in mandibular prognathism]. PMID- 3333503 TI - [The changes of palatal soft tissue following lateral expansion of upper dental arch. I. Study on the stressed palatal soft tissue by heavy force and the change of vascular permeability]. PMID- 3333504 TI - [Integrated orthodontic management system for virtual three-dimensional computer graphic simulation and optical video image database--supported system for diagnosis and treatment planning]. PMID- 3333505 TI - [Radiographic analysis of the movement pattern of the mandibular condyles--an appraisal of subtraction procedure in computed radiography system]. PMID- 3333506 TI - [The direct bonding method for porcelain and ceramic brackets]. PMID- 3333507 TI - [Bond strength of new ceramic bracket enhanced by silane coating]. PMID- 3333508 TI - [Three-dimensional reconstruction from X-ray computerized tomographic films with personal computer system]. PMID- 3333509 TI - [The initial tissue response of the rat sagittal suture to mechanical expansion. Response to two kinds of initial force]. PMID- 3333510 TI - [Changes of the microvascular pattern in the midpalatal suture occurring in association with rapid palatal expansion]. PMID- 3333511 TI - [The enamel surface characteristics after removal of orthodontic adhesives]. PMID- 3333513 TI - Scapulothoracic dissociation (closed avulsion of the scapula, subclavian artery, and brachial plexus): a newly recognized variant, a new classification, and a review of the literature and treatment options. AB - Scapulothoracic (ST) dissociation is a closed complete traumatic forequarter amputation manifested by a flail pulseless arm and well-defined roentgenographic findings. These roentgenographic findings were previously reported to be lateral displacement of the scapula and either acromioclavicular separation (17) or displaced clavicular fracture (20). In this paper we present four patients with ST dissociation who had a previously unreported combination of roentgenographic findings: lateral displacement of the scapula and sternoclavicular separation. Polytrauma was present in all previously reported cases of patients with ST dissociation. We present one patient, however, in whom ST dissociation is an isolated finding. A review of the literature, and a review of treatment options that includes some combination of amputation, shoulder arthrodesis, prosthetic fitting, and reconstructive tendon transfers, are presented. PMID- 3333512 TI - A double-blind clinical trial of prophylactic cloxacillin in open fractures. AB - In 100 patients with first-, second-, and third-degree open fractures, a randomized, double-blind study was carried out to compare prophylactic cloxacillin and placebo. Prophylaxis was started preoperatively and continued for 10 days. The standard fracture treatment consisted of operative stabilization, mostly by means of plates or external fixators. In the cloxacillin group two infections were observed as compared to 12 in the control group. This difference was significant. PMID- 3333514 TI - Acute anterior compartmental syndrome of the thigh following contusion. A case report and review of the literature. AB - Contusion is a rare cause of acute compartmental syndrome in the thigh. To date, no case report has described blunt trauma precipitating this limb-threatening condition. The patient in this case report developed rapidly progressive signs and symptoms which required emergency fasciotomy. Delayed primary closure was possible and recovery was complete. The etiologies, diagnosis and management of thigh compartmental syndrome are reviewed. PMID- 3333515 TI - Flexible intramedullary nailing of long bone fractures: a review. PMID- 3333516 TI - Treatment of nonunion of fractures in the epiphyseal-metaphyseal region of long bones. AB - Twenty-four consecutive patients with fracture nonunion in the metaphyseal epiphyseal areas of long bones were surgically treated. Average time from injury to treatment of the nonunion was 10 months, and average follow-up time after surgical treatment was 29 months. Eight patients with infected nonunions had initial debridement procedures; three of these patients then had placement of external fixators and bone grafting. The remaining five patients and 13 others were then treated by open reduction and internal fixation alone or with the addition of autogenous cancellous bone grafting. Single or double plates and screws were used. Arthrolysis, joint manipulation, and intensive postsurgical exercises were considered necessary to regain joint function. One patient underwent a hemiarthroplasty, and two others underwent arthrodesis as the initial nonunion treatment. Twenty of the 21 patients not treated by arthrodesis or arthroplasty healed their fractures in an average time of 7 months. Fifty-two percent of the patients achieved good or excellent range of motion (ROM) of the contiguous joint, with 70% of the patients reporting no pain in this joint. These fractures have excellent intrinsic healing capability because they occur in anatomical regions with a normally abundant circulation. We recommend stable fixation, with the need for bone grafting only in defect nonunions, together with intra- and postoperative joint mobilization to obtain a satisfactory functional end result. PMID- 3333517 TI - Current status of locked intramedullary nailing: a review. PMID- 3333518 TI - Tibial plateau fractures: definition, demographics, treatment rationale, and long term results of closed traction management or operative reduction. AB - Results of a decade of experience with 988 tibial plateau fractures are presented. Maximum plateau depression was measured on initial and follow-up x-ray studies, and knee instability was clinically evaluated to identify minor and major fractures as a guide to management. Demographic, treatment, and complication data were gathered prospectively in 753 fractures. Four hundred thirty-seven "major" tibial plateau fractures (44% of cases) were treated operatively; the remainder were treated by traction. Three hundred twenty patients who sustained only a plateau fracture were followed from 1 to 10 years, with an average of 3.7 years. Nonsurgical treatment included Buck's traction (89% of closed treatment cases) or a "knee exerciser" device utilizing skeletal traction in a Hodgson-Pearson apparatus. Early intermittent passive and active knee motion was encouraged. The complication rate of traction was 8%. The complication rate in operated patients was 19%, much of which was due to infection. Methods for objective and subjective scoring of both traction and operative results were developed and utilized. Results show that anatomic reduction of plateau fractures, in addition to early motion, is a major factor contributing to successful management of this potentially disabling injury. PMID- 3333519 TI - [Severity of aortic stenosis assessed by Doppler techniques]. AB - Continuous wave (CW) Doppler ultrasound has facilitated accurate estimates of pressure gradient (PG) across a stenotic valve. However, the severity of stenosis cannot be assessed using PG alone because it is dependent on actual flow across the valve. In this study, Doppler techniques were used to predict PG and aortic valve areas (AVA) in adults with aortic stenosis (AS). Fifty-four adult patients undergoing cardiac catheterization for suspected AS were prospectively evaluated. There were 28 men and 26 women, who ranged in age from 25 to 68 years with a mean of 56 years. These Doppler ultrasound studies were performed using a 2 MHz transducer and an Aloka SSD-730. With CW Doppler ultrasound, the highest velocities of the aortic jet were recorded from an apical approach. Left ventricular outflow flows were recorded about 1.0-1.5 cm below the aortic annulus using high PRF. Doppler waveforms were analyzed for the AT/ET (AT: acceleration time, ET: ejection time), and Doppler PG was calculated from the maximum velocity (V) of the aortic jet based on a modified Bernoulli equation (PG = 4V2), and aortic valve area was obtained using the continuity equation-(AVA = left ventricular outflow tract stroke volume divided by AS jet velocity integral). These data were compared with hemodynamic data obtained from cardiac catheterization. The following results were obtained: 1. In eight patients with substantial aortic regurgitation, whose maximum catheter PG were from 20 to 45 mmHg, the AT/ET was less than 0.30. The ratio of AT/ET correlated with the peak velocity of the aortic jet (r = 0.88) and the maximum PG (r = 0.87) obtained from cardiac catheterization. 2. In 46 patients with AS, the maximum PG by CW Doppler showed an excellent correlation with maximum catheterization PG (r = 0.97, SEE 6 mmHg), and the mean PG as calculated by the two techniques also disclosed a good correlation (r = 0.97, SEE 5.4 mmHg).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3333520 TI - Abnormalities of myelination of the central nervous system associated with congenital tremor. PMID- 3333521 TI - Effects of manipulation of sodium balance on erythrocyte sodium transport. AB - The effects of changing sodium balance on blood pressure (BP) and erythrocyte sodium transport were investigated in normotensive first-degree relatives of hypertensive patients and control subjects randomised to receive low and high salt diets for two weeks, separated by a two week washout period. Changing from high to low salt intake produced a significant fall in standing diastolic pressure (DBP) in control subjects but not in the offspring of hypertensive patients. In both groups erythrocyte sodium efflux was not changed significantly by either manoeuvre, but the relatives had a significantly higher ouabain insensitive sodium efflux rate constant on both the low and the high salt diet compared to the controls (P less than 0.05). These results are not in keeping with the hypothesis which suggests the release of a humoral sodium pump inhibitor in response to sodium loading but lend support to the view that there is a disturbance of membrane permeability to sodium in subjects genetically prone to hypertension. PMID- 3333522 TI - The effect of reduced alcohol consumption on blood pressure: a randomised, controlled, single blind study. AB - A randomised, controlled, single blind trial was conducted in office workers with mild hypertension (systolic blood pressure (SBP) 140 to 180 mmHg, diastolic blood pressure (DBP) 90 to 110 mmHg) to determine the effect of decreasing alcohol consumption. After a baseline examination, 50 male volunteers aged 30 to 59 were randomised to two groups. Group A were told to abstain from or reduce alcohol consumption for two weeks, while group B were instructed to maintain their usual alcohol consumption. Complete records were obtained on 49 subjects. The daily alcohol consumption of groups A and B at baseline was similar, i.e. 71.9 ml and 72.5 ml of ethanol, respectively, and changed to 16.1 ml and 62.9 ml, respectively, during the experiment. After two weeks, group A were asked to resume their normal consumption whilst group B were asked to reduce or abstain (phase II). However in view of a treatment period interaction, statistical analysis was confined to phase I. During phase I, group A, whose alcohol consumption had reduced, showed decreases of 5.8 and 7.1 mmHg in SBP during the the first and second weeks, respectively. In group B, these decreases were only 0.6 and 1.9 mmHg, respectively. The difference between the falls in SBP in groups A and B was significant (P = 0.005) as judged by analysis of variance. The DBP also decreased, but there was no significant difference between the decreases in the two groups. Changes in gamma-glutamyl-transpeptidase, a biochemical marker of alcohol consumption, from the initial values to the end of phase I were significantly different in groups A and B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333523 TI - Atenolol or propranolol in hypertensive patients poorly controlled on captopril and frusemide. AB - Eighteen patients whose clinic blood pressure (BP) remained over 95 mmHg despite treatment with captopril 50 mg twice daily plus frusemide 40 mg twice daily were randomised in a crossover study to four weeks' treatment with once daily atenolol 100 mg, slow release propranolol 160 mg or placebo. The reduction in BP on atenolol was superior to that on both propranolol and placebo. The mean supine BP 24 hours post dosing were 177/110 mmHg (placebo), 173/109 mmHg (propranolol) and 164/100 mmHg (atenolol). The corresponding mean heart rates were 77 bpm (placebo), 63 bpm (propranolol) and 62 bpm (propranolol) and 62 bpm (atenolol). The difference in hypotensive efficacy between atenolol and propranolol is not readily explained but our study shows that atenolol has a clinically useful supplementary effect on BP. Refractory hypertension remains an important clinical problem and further studies are required to establish the optimum combination of drugs that should be used with captopril in order to achieve 'target' BP in patients with moderate to severe hypertension. PMID- 3333524 TI - Atenolol improves blood pressure control in patients taking captopril and frusemide. AB - In a double-blind randomised cross-over study atenolol 100 mg daily and matching placebo were given to 14 patients whose blood pressure (BP) was uncontrolled on a fixed dose of captopril and frusemide. Atenolol produced a further reduction in both supine (170/105 mmHg to 163/94 mmHg) and standing (171/114 mmHg to 160/96 mmHg) BP and a significant fall in pulse rate and plasma renin activity (PRA). This fall in BP showed a highly significant correlation with pre-treatment plasma renin levels. No adverse side effects were encountered during the study. Previous suggestions that beta-blockade had no additional hypotensive effect in patients receiving captopril were not substantiated. For patients whose BP was poorly controlled with captopril and a diuretic, a selective beta-blocker is suggested as a useful third line agent. PMID- 3333525 TI - Neurohumoral mechanisms and left ventricular hypertrophy: effects of hygienic therapy. AB - To determine the effects of hygienic (non-drug) therapy on blood pressure (BP) control and its relationship to sympathetic tone and left ventricular mass (LVM) in primary hypertension, plasma norepinephrine (NE) and renin activity (PRA), LVM, and nutritional and behavioral status were assessed in 76 borderline to mild hypertensives. Pretherapy plasma NE was related to diastolic blood pressure (DBP) and PRA (r = 0.24, P less than .05 and r = 0.37, P less than .01, respectively). Plasma NE of high renin patients (221 +/- 52) (mean +/- SD) was greater than that of normal renin patients (159 +/- 61, ng/l, P less than .01). LVM was related to systolic blood pressure (SBP) (P less than .001), DBP (P less than .01) and urinary sodium (P less than .05), and inversely related to PRA (P less than .01). Septal wall thickness was related to hostility (r = 0.42, P less than .05). After seven weeks of hygienic therapy, DBP was reduced by 6 mmHg (P less than .01). The change in SBP was related to baseline plasma NE (P less than .05) and inversely related to LVM (P less than .05). These results suggest that raised sympathetic tone may be a pathogenic factor in primary hypertension and that hygienic therapy lowers BP more effectively in patients with raised sympathetic tone and low LVM. PMID- 3333526 TI - Hypertension following renal trauma. AB - Renovascular hypertension is an unusual complication of renal trauma, occurring in approximately 5% of cases. It occurs predominantly in young males following road traffic accidents (RTA) or blunt abdominal trauma. The interval between injury and development of hypertension varies from two days to 14 years but presentation may be acute with hypertensive encephalopathy. Hypertension developing within a few months of injury may be treated conservatively. Conservative treatment more than one year after injury is associated with an increased risk of persistent hypertension. All cases of renal trauma should be followed with regular blood pressure (BP) recording for at least the first year after injury. PMID- 3333527 TI - Why has the primary prevention of myocardial infarction in the treatment of hypertension been so elusive? AB - The pathogenesis of the two main killers in hypertension, myocardial infarction (MI) and stroke, differs. Prevention of strokes, about a third of which result from haemorrhage, appears more immediately responsive to the level of blood pressure (BP). MI reflects the end stage of a slow underlying atheromatous process of the coronary arteries and lowering BP can, at best, hope only to slow this process and make less likely the eventual plaque rupture and resultant occlusive thrombosis and infarction. Practically all the randomised trials have confirmed that the treatment of all grades of hypertension, down to a treated diastolic BP level of perhaps about 95 mmHg, reduces the incidence of fatal and non-fatal stroke by about 40-50%, though only two classes of antihypertensive agent i.e. diuretics (+/- other agents) and beta-blockers (+/- diuretics), have actually demonstrated this benefit. It is possible, in the elderly, that excessive lowering of systolic BP (SBP) (to below about 140 mmHg) might increase the number of deaths from stroke. Blood lipid changes which constitute coronary risk factors in untreated hypertensive patients should not be regarded in the same light if beta-blocker induced. Animal data suggest that beta-blockers inhibit catecholamine induced cardiovascular damage and modify coronary atheroma formation in the presence of stress and/or high cholesterol diets (in spite of blood lipid changes). Evidence in the moderate to severely hypertensive man also suggests that in spite of beta-blocker induced increases in blood triglyceride levels the incidence of deaths from MI markedly decreases over a ten year period in those whose SBP is well controlled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333528 TI - Preoperative lateralisation of aldosteronomas by aldosterone/cortisol ratios in adrenal venous plasma. AB - Data from adrenal scintigraphy with 6 beta-[131I]-iodomethyl-19-norcholesterol (AS), computed tomography (CT), adrenal venography and adrenal venous sampling were compared for their accuracy in locating small aldosteronomas in 17 patients. Final confirmation of location was by surgery. Seventeen out of 18 adrenals whose aldosterone/cortisol (A/C) ratio was 5.0 x 10(-3) or higher were found to have aldosteronomas (94.4%). All 14 adrenals whose A/C ratios were less than 5.0 x 10( 3) contained no aldosteronomas (100%). AS successfully lateralised nine out of 17 aldosteronomas (52.9%), CT 3 out of 5 (60.0%), adrenal venography 12 out of 17 (70.6%), adrenal venous aldosterone concentration 12 out of 15 (80.0%). The most frequent problem with adrenal venous sampling was the varying degrees of mixture with non-adrenal venous blood, mainly from renal vein and inferior vena cava blood. The A/C ratio of adrenal venous plasma proved to be the most useful diagnostic tool, using cortisol concentration as an indicator of any non-adrenal venous mixture. PMID- 3333529 TI - Apparent improvement in diabetic autonomic neuropathy induced by captopril. AB - Eight diabetic subjects with moderately elevated blood pressure (BP) (systolic (SBP) greater than 140 and/or diastolic (DBP) greater than 90 mmHg) were studied. Each had evidence of mild asymptomatic autonomic neuropathy (impairment of forced sinus arrhythmia). The effect of a single oral 25 mg dose of captopril on BP and some aspects of autonomic function was compared with matched placebo in a double blind, cross-over study. Resting supine SBP and DBP fell significantly (P less than 0.01) over 90 minutes following captopril, indicating that the hypotensive effect of the drug was not dependent on intact autonomic function. There was no significant change in resting heart rate. The bradycardic response to apnoeic face immersion was significantly (P less than 0.01) enhanced following captopril. Sinus arrhythmia did not change. The BP responses to standing and to the cold pressor test were unaffected. There was no exacerbation of postural hypotension. The ingestion of a single dose of captopril appears to increase vagal function, without affecting sympathetic nervous function, in diabetics with evidence of mild vagal impairment. PMID- 3333531 TI - Psychophysiologic aspects in essential hypertension. AB - Epidemiologic and experimental studies disclosed that the sympathetic nervous system might play a pivotal role in the pathogenesis of essential hypertension. Although systolic pressure exhibits a weak endogenous rhythm, diurnal fluctuations of arterial pressure are provoked primarily by physical or emotional stress factors. The magnitude of the cardiovascular response, however, varies widely from individual to individual. Subjects at high risk of future hypertension,--such as those with a positive history of familial hypertension, high resting heart rate, or transient increase in arterial hypertension--revealed blood pressure hyperresponsiveness to stress stimuli mediated by an overreactivity of the sympathetic nervous system. Furthermore, cardiovascular reactivity to mental arithmetic tasks and to traffic noise put a patient at high risk of developing arterial hypertension. In women, exaggerated cardiovascular response to stress stimuli appeared to be mitigated by estrogens, whereas oral contraceptives overrode this 'protective' effect of estrogens. At a certain point, repeated episodes of high stress blood pressure could produce structural vascular changes finally inducing sustained hypertension. PMID- 3333530 TI - Predictors of blood pressure change in a series of controlled dietary intervention studies. AB - Three controlled dietary intervention studies were carried out in 1981-1983 in North Karelia, Finland, to asses the impact of dietary fat intake modification on blood pressure (BP). All these studies involved middle-aged men and women in rural or semirural areas and comprised a baseline period, a six week (or 12 weeks in the third study) intervention period and a four to six week return to baseline. During the intervention period the total fat intake was reduced from 39% to 24% of energy and the polyunsaturated/saturated (P/S) ratio increased from 0.2 to 0.4-1.2. In all groups energy intake was kept constant. For the present report data from the three studies were pooled for a series of stepwise regression analyses to predict changes in BP with different dietary changes. For both systolic (SBP) and diastolic (DBP) blood pressure, change in polyunsaturated fatty acid intake was the strongest dietary predictor of BP change. Changes in body weight, total fat intake, urinary sodium and potassium did not have significant predictive power in any of the analyses. The findings support the hypothesis that modification of dietary fat intake is a significant predictor of change in BP. PMID- 3333532 TI - Phaeochromocytoma presenting with cardiogenic shock and acute renal failure. AB - A patient with a 12 hour history of headache, breathlessness and hypotension developed acute renal failure necessitating haemodialysis for 12 days. During recovery she developed hypertension, tachycardia and facial flushing. Investigations revealed a right adrenal phaeochromocytoma. Whilst postural hypotension is common in phaeochromocytoma, profound shock with acute renal failure is rare. This may have been precipitated by concomitant drug therapy, myocardial necrosis or by necrosis within the tumour. PMID- 3333533 TI - Effect of drugs on Trypanosoma cruzi and on its interaction with heart muscle cell "in vitro". AB - Megazol, nifurtimox, benznidazol and allopurinol were investigated, by light and electron microscopy, for their action on T. cruzi. Both the direct effect upon amastigote and trypomastigote forms and the effect upon the interaction of heart muscle cells (HMC) with bloodstream trypomastigotes were studied. The proliferation of amastigotes in Warren medium was inhibited in a dose-dependent manner by megazol, nifurtimox and benznidazol. Treatment of amastigotes (25-50 microM/24 h) and trypomastigotes (25 microM/24h) led to several ultrastructural alterations in the parasites. These three drugs also had a potent effect on the treatment of infected heart muscle cells when added at the beginning of the interaction or after one or three days of infection. The interiorized parasites showed a similar pattern of ultrastructural alterations as observed by the direct effect on the amastigotes. The primary heart muscle cell culture proved to be a suitable model for the study of drugs on intracellular parasites. Likewise, the amastigote proliferation in axenic medium was shown to be an adequate assay for an initial trial of drugs. These parameters seem very reliable to us for a systematic investigation of the mechanism of action of new drugs. PMID- 3333534 TI - Short- and long-term effects of proallatotoxin (ethoxyprecocene II) on Rhodnius prolixus females. AB - Oogenesis and oviposition can be inhibited in female of Rhodnius prolixus by means of short-term experiment (first reproductive cycle) of a single dose of ethoxyprecocene II given by ingestion. The inhibition is dose-dependent as measured by oocyte growth, egg maturation and egg deposition. In a long-term experiment (second and third reproductive cycles) egg production and oogenesis can be partially or totally re-established by subsequent blood meals without ethoxyprecocene II. These findings suggest that in female R. prolixus, damage caused to corpus allatum by ethoxyprecocene II, in certain cases, is not irreversible. PMID- 3333535 TI - [Specific immunization in cutaneous leishmaniasis--a review]. PMID- 3333537 TI - Per rectal extrusion of a ventriculo peritoneal shunt catheter. A case report. PMID- 3333538 TI - Coronary artery bypass: Missouri's experience. A case study in the public release of sensitive data. PMID- 3333536 TI - [Memoir of the Memorias. Development of malaria hematozoa resistant to quinine. By Arthur Neiva, 1910]. PMID- 3333539 TI - Ventricular standstill in acute inferior myocardial infarction with high degree AV block. PMID- 3333540 TI - Comparison of non-invasive carotid tests with angiography in assessing carotid stenosis. PMID- 3333541 TI - The health insurance experience and status of Missouri renal transplant recipients. The Scientific Advisory Board, National Kidney Foundation of Eastern Missouri and Metro East, Inc. PMID- 3333542 TI - Joseph Warren, M.D.--physician and patriot. PMID- 3333544 TI - Missouri State Medical Association. Roster of members by component society. PMID- 3333543 TI - Missouri State Medical Association. Alphabetical roster of members. PMID- 3333546 TI - [A clinical study on adhesion bridge and tooth movement]. PMID- 3333545 TI - Synchronous renal and pancreatic transplantation. Experience in type I diabetics with end-stage renal disease. PMID- 3333547 TI - [Studies on photopolymerized crown and bridge resin. Part 1. Physical properties of Dentacolor]. PMID- 3333548 TI - [Periodontal evaluation of abutment teeth. Part 2. Correlation between gingival fluid volumes and pH values in gingival crevices and periodontal pockets]. PMID- 3333549 TI - [Adaptability of post core constructed by die-investing technique. Comparison in adaptability with post core constructed by die-pattern technique]. PMID- 3333550 TI - [Basic studies on Konuskronen by using the finite element method. Part 2. Stress analysis of mandibular distal-extension removable partial denture]. PMID- 3333551 TI - [Studies on the influences of the indirect retainers on the displacements of the denture bases and the abutment teeth. Part I. Their forms and presence or absence ]. PMID- 3333552 TI - [Clasping system with rotational path of insertion. Part 1. Retention of denture]. PMID- 3333553 TI - [A clinical study on gum displacement--temporary crown devised for gum displacement]. PMID- 3333554 TI - [Clinical studies of fixed prosthetic appliances on marginal gingivae. Part 1. Influences concerning the construction of fixed prosthetic appliances on marginal gingivae]. PMID- 3333555 TI - [Clinical studies of fixed prosthetic appliances on marginal gingivae. Part 2. Evaluation of fixed prosthetic appliances after a 3-year period]. PMID- 3333556 TI - [Stress analysis on distal-extension removable partial denture using finite element method. Part 1. The stress distribution on different connection types of retainers]. PMID- 3333557 TI - [Properties and adhesive strength of trial gold alloy for an adhesion bridge and an adhesion splint]. PMID- 3333558 TI - [The influence of environmental temperature, humidity and methods to dry the etched enamel surface on the adhesive strength of dental adhesive resin 'Panavia EX']. PMID- 3333559 TI - [Effects of random position on the abutment form for a full cast crown. The left upper first molar]. PMID- 3333560 TI - [Stress distribution of abutment tooth with core and fixed prosthetic appliance]. PMID- 3333561 TI - [The development of ultrasonic diagnostic equipment for dental use]. PMID- 3333562 TI - [Analyzing system for artificial teeth arrangement using the personal computer. Application of finite element method for education and clinics]. PMID- 3333563 TI - [High performance liquid chromatography analysis of salivary proteins concerning the retention of denture base]. PMID- 3333564 TI - [Pressures produced in a tray during impression procedures. Maxillary edentulous impressions]. PMID- 3333565 TI - [An air-powder abrasive system for prosthetic clinical application. Part 2. The effect of air-powder abrasive system on gingiva]. PMID- 3333566 TI - [Denture stomatitis. III. Microbiological study]. PMID- 3333568 TI - [Clinical investigations on the use of the third molar as an abutment tooth for removable partial denture]. PMID- 3333569 TI - [Pressures on supporting tissues under complete denture during functions. Concerning the effects of the arrangement of artificial posterior teeth]. PMID- 3333567 TI - [Research of condylar movements on protrusive and lateral jaw positions (1st report)]. PMID- 3333570 TI - [The accuracy of stone casts. The development of a three-dimensional measurement system and the influence of tray design on alginate impressions]. PMID- 3333571 TI - [Mechanical studies on cast clasps of a superelastic Ni-Ti alloy. Part 2. Deflection behavior caused be repeated bending forces]. PMID- 3333572 TI - [Viscosity of saliva in relation to denture retention. Part 2. Viscosity of mediating fluid in relation to retention of denture]. PMID- 3333573 TI - [The stress analysis on distal-extension removable partial denture using finite element method. Part 2. The stress distribution on different splinting]. PMID- 3333574 TI - [A compact system for analyzing mandibular movements with the application of an infrared sensor. Outline and precision of the system]. PMID- 3333575 TI - [Experimental study on denture stomatitis. Effect of carbohydrates on initiation and aggravation of inflammation induced by Candida albicans]. PMID- 3333576 TI - [Statistics of prosthetic restorations]. PMID- 3333577 TI - [Clinical study on the effect of temporary cements to marginal gingiva]. PMID- 3333579 TI - [The adherence of Candida albicans to acrylic]. PMID- 3333578 TI - [Mechanical analysis on design parameters of adhesion bridge. Part 3. Adhesive strength of adhesion bridge under shearing loads]. PMID- 3333580 TI - [Effects of coping designs on abutment teeth displacements under overdenture applications]. PMID- 3333581 TI - [Investigation on the method of reinforcement for swagged metal denture]. PMID- 3333582 TI - [Mechanical properties of swagged stainless steel denture with 4-META adhesive resin]. PMID- 3333583 TI - [Accuracy of post impression in various directions. Combined reversible/irreversible hydrocolloid impression]. PMID- 3333584 TI - Good design, the secret of successful complete denture prostheses. PMID- 3333585 TI - [Laboratory-made stud attachment. Report III. Effect of kinds of metal alloys on fatigue]. PMID- 3333587 TI - [Caries-reduction of overdenture abutment. Part 2. Solubility of the embedded tannin-fluoride preparation]. PMID- 3333586 TI - [Three-dimensional relation between lip surface and upper anterior teeth]. PMID- 3333588 TI - [Application of ferromagnetic alloy for prosthodontics. Part 5. Application of magnetic attachment for prosthetically hopeless teeth]. PMID- 3333589 TI - [Buccal and lingual crown contours. The influences of the self-cleansing effect of food and mechanical cleansing]. PMID- 3333590 TI - [Filling materials with a tannin-fluoride preparation in denture base. Part 1. In relation to the mixing ratio of preparation to the autopolymerizing resin]. PMID- 3333591 TI - [An expert system for designing removable partial dentures. Part II. The role of the database constructed with clinical cases]. PMID- 3333592 TI - [Vertical displacement of Konus retainers in removable partial denture. Longitudinal measurements using a fixed microgap sensor in the oral cavity]. PMID- 3333593 TI - [Gradient SDS-PAGE analysis of proteins and glycoproteins in human palatine saliva]. PMID- 3333594 TI - Computed tomography of the lower extremity. Part I. PMID- 3333595 TI - Os odontoideum--a review. PMID- 3333596 TI - Traumatic dislocation of the knee: a report of 30 cases and literature review. AB - Traumatic dislocation of the knee, an uncommon injury, is sustained as the result of violent trauma. Thirty documented cases of complete traumatic dislocation of the tibia from the femur are identified and retrospectively reviewed. Twenty had adequate documentation with a minimum two-year follow-up to evaluate the results of operative versus nonoperative treatment of this ligamentous injury. Nonoperative treatment can result in a functional knee depending on the patient's demands. However, early operative repair, followed by early limited motion (cast bracing), and aggressive physical therapy to regain motion, are recommended in young active patients. Prolonged immobilization postoperatively should be avoided. PMID- 3333597 TI - Small bone grafts of an ulna nonunion. AB - The treatment of nonunions of the ulna has included direct current, compression plating, and bone-grafting. A case of compression plating and bone grafting of an ulnar nonunion in which the bone graft was obtained from the iliac crest with a Craig biopsy needle is described. This procedure allows bone graft to be harvested quickly with minimal postoperative morbidity. The procedure can be used in primary plating of fractures as well as in nonunions. PMID- 3333598 TI - [Once more on the effects of the Chernobyl accident]. PMID- 3333599 TI - [Computerized-tomographic examinations of the parotid gland. I. Methods of examination and radiological anatomy]. PMID- 3333600 TI - [Computerized-tomographic examinations of the parotid gland. II. CT symptomatology of tumors of the parotid gland]. PMID- 3333601 TI - [Radioactive P-32 labeled microspheres in the treatment of neoplasms of the parenchymatous organs]. PMID- 3333603 TI - [Experience with 1-year use of the Thomson set for digital subtraction angiography]. PMID- 3333602 TI - [Radioisotope infusion cisternography in the diagnosis of cerebrospinal rhinorrhea]. PMID- 3333604 TI - [Roentgenological evaluation of the condition of the urinary tract in children with urethral valve]. PMID- 3333605 TI - [Pulmonary asbestosis. I. Pathomechanism and pathomorphology of the disease]. PMID- 3333606 TI - [Pulmonary asbestosis. II. Roentgenological diagnosis and other methods of examination]. PMID- 3333607 TI - [Bibliography of Polish publications on ultrasonic diagnosis 1980-1986]. PMID- 3333608 TI - Chronopharmacology: a new perspective in pharmacology. AB - Vital signs and several constituents of the serum and urine exhibit a circadian rhythm, and the same is true for the onset of several diseases. The rhythmic changes in the blood volume, functions of the liver and kidney, etc., have implications for drug availability, and the circadian changes should be taken into account in pharmacokinetic studies. These changes are the subject of chronopharmacokinetics. In addition to the circadian rhythm in changes in drug absorption, elimination and bioavailability, a rhythm of the intensity of drug effects and side-effects may also be observed: this is the domain of chronopharmacodynamics. Several examples demonstrate that chronopharmacokinetic and chronopharmacodynamic results support the view that the temporal organization of the organism is an important variable influencing the action of drugs. PMID- 3333609 TI - The retina as a model neural tissue: comparative studies on retinal and brain aminergic mechanisms. AB - A body of morphological, metabolic and electrophysiological data indicate that the isolated retina maintains for several hours nearly all of its physiological activity (including responsiveness to light), and therefore can be successfully used for in vitro studies. In this paper, results of comparative investigation of the dopaminergic, serotoninergic and histaminergic mechanisms in the rabbit retina and brain, performed in the author's laboratory, are presented and discussed. The existence of many similarities in the analyzed aminergic mechanisms between both tissues supports the notion that the isolated retina may serve as an in vitro model tissue for study of the central nervous system. PMID- 3333610 TI - Tolerance to antiepileptic drug effects. Experimental evidence and clinical significance. AB - The development of tolerance to the anticonvulsant effect of drugs has been demonstrated in animal experiments for most antiepileptic drugs. This evidence is reviewed, including the methodological approach and the differentiation into 'metabolic' and 'functional' tolerance. Clinical evidence of the development to antiepileptic drug effects is equivocal: The existence of tolerance is generally accepted for the benzodiazepines which often lose their antiepileptic effect during prolonged treatment. For this group of drugs tolerance is a major clinical problem. With other antiepileptic drugs some degree of tolerance may develop, but this can hardly be recognized as such under clinical conditions, and is thus not considered to be of major importance for treatment of epilepsy. PMID- 3333611 TI - In vitro electrophysiological evidence predicting anticonvulsant efficacy of memantine and flunarizine. AB - Electrophysiological assays on mammalian central neurons in monolayer dissociated cell culture allow classification of clinically used anticonvulsant drugs on a mechanistic basis and predict their clinical spectrum of anticonvulsant efficacy consistently in comparison with data from animal models. Clinical anticonvulsant efficacy of memantine and flunarizine against tonic-donic and partial seizures is predicted on the basis of ability to limit sustained high efficacy frequency repetitive firing of sodium-dependent action potentials and to suppress depolarizing burst firing of neocortical, hippocampal and spinal cord neurons in cell culture. Effects on voltage-sensitive sodium channels, and possibly potassium channels, may explain, at least in part, the mechanism of anticonvulsant efficacy of memantine and flunarizine. PMID- 3333612 TI - The seizures induced by pilocarpine: behavioral, electroencephalographic and neuropathological studies in rodents. AB - Seizures produced by systemic administration of pilocarpine hydrochloride, a cholinergic muscarinic agonist, in rodents are proposed as a useful animal model of epilepsy. Pilocarpine-induced seizures in rats and mice are characterized by sequential development of behavioral and electrographic signs, which are followed by widespread damage to the forebrain (hippocampus, amygdala, thalamus, olfactory cortex, neocortex and substantia nigra). Spontaneous seizures may be observed in the long-term period following the administration of convulsant doses of pilocarpine. In experiments designed to examine neuronal networks engaged in the generation and spread of pilocarpine-induced convulsions, a marked role for the basal ganglia is demonstrated. The caudate-putamen, the substantia nigra and the entopeduncular nucleus were found to govern the propagation of seizures produced by pilocarpine. The antiepileptic potential of drugs (diazepam, clonazepam, phenobarbital, valproic acid and trimethadione) against pilocarpine-induced convulsions correlates with their depressant action on the spontaneous activity of non-dopaminergic cells in the substantia nigra. Developmental studies show age dependent differences in the convulsant response of rats to pilocarpine and status epilepticus are first noted in 2-3 week-old rats, but there is no clear cut correlation between seizures and evolution of brain damage at this age. The adult pattern of the damage to forebrain is seen after a delay of 1-2 weeks relative to the development of seizures and status epilepticus. The research on the pilocarpine model of convulsions and other cholinergically mediated seizure syndromes may be of value for designing new therapeutic approaches to epilepsy in. PMID- 3333614 TI - Opioid peptides in relation to antinociception. AB - Three families of endogenous opioid peptides, each derived from distinct precursor, as well as their localization, affinity and interaction with different subtypes of opioid receptors are described. The release of opioid peptides upon various stimulation procedures is also presented. The emphasis is made on the role of opioid peptides in analgesia by describing their antinociceptive potency and discussing the role of peptides deriving from the different precursors in conveying the acute pain stimuli and on the changes in activity of opioid peptide systems in chronic pain. PMID- 3333613 TI - Effects of antiepileptic drugs in electrophysiological tests. AB - Methods of the study of antiepileptic drugs activity by means of analysis of their effects on bioelectrical ictal phenomena in the animal brain are described. The paper deals especially with EEG signal processing methods. Application of various nonparametric models (e.g. interval-amplitude scatter plots, power spectra analysis) as well as parametric models (e.g. autoregressive model, segmentation analysis) is discussed. A discriminative approach to some of these methods (especially to autoregressive model) is also presented. Special attention is stressed on the value of these methods for the study of anticonvulsant drugs activity. PMID- 3333615 TI - Pharmacological and human studies with a highly potent opioid peptide, D-Met2, Pro5-enkephalinamide. AB - D-Met2, Pro5-enkephalinamide (DMPEA) is an opioid peptide having analgesic activity in animals more potent after intravenous administration than morphine. It is less toxic but in animals it showed a higher dependence capacity than morphine. Besides analgesia DMPEA produces in rodent behavioral symptoms similar to those evoked by morphine or beta-endorphin, resembling the actions of neuroleptica. In human trials DMPEA was found to produce unpleasant sensations, no euphoria, and sometimes even dysphoria. DMPEA increases the serum levels of prolactin, growth hormone and, to a less extent, of TSH. Those effect of DMPEA on pituitary hormones. Finally, the human studies indicated that DMPEA antagonized pain (measured with the submaximum effort tourniquet technique), but did not affect adversely and even improved attention and short-term memory; it had no effect on the long-term memory. As the subjective effects of DMPEA are not pleasant, and no patient desired to obtain another treatment, some optimism as to low habit-forming properties of DMPEA may be justified. PMID- 3333616 TI - [The influence of post-core metal's composition on tooth discoloration]. PMID- 3333617 TI - [Three orthodontic cases of prosthodontic treatment to correct extensive congenital absence of teeth]. PMID- 3333618 TI - [Transplantation antigenicity, osteoinductivity and mechanical property of allogenic bones treated under various methods]. PMID- 3333619 TI - [The influence of the arrangement position of upper posterior artificial teeth on pronunciation. Japanese sounds, the point of articulation of which is on posterior palate]. PMID- 3333620 TI - [Ultrastructure of myoepithelial cells in rat sublingual gland. A study using immunohistochemistry, scanning electron microscope and heavy meromyosin decoration methods]. PMID- 3333621 TI - Contribution of computerized tomography to the diagnosis of non-tumorous neuropaediatric diseases. PMID- 3333622 TI - Strategies for the development of amperometric enzyme electrodes. AB - There are now a number of distinct strategies which can be employed to make amperometric enzyme electrodes. These include the use of homogeneous mediators, modified electrodes and organic conducting salts. In this paper we review these strategies and discuss their application to NAD(P)H dependent dehydrogenase and flavoprotein based biosensors. In addition we discuss recent work on the immobilisation of glucose oxidase in polypyrrole, poly-N-methylpyrrole, polyaniline and polyphenol films electrochemically grown at the electrode surface and on the covalent attachment of redox mediators to glucose oxidase in order to achieve direct electron transfer to the electrode. PMID- 3333623 TI - Stabilizing blood glucose with a novel medical expert system. AB - In health, metabolism is elegantly coordinated. Failure of an underlying process (as occurs in diabetes) disrupts the coordination and impacts on the global status of the affected individual. It takes a medical expert to intervene and restore order. Chaotic processes prevail at all times in biological systems and their behaviour in sickness degenerates between medical interventions. We have explored the use of an expert system to substitute for the physician between interventions and demonstrated its ability to maintain order and thus significantly improve control of blood glucose. PMID- 3333624 TI - [Thromboembolus of the right heart. Sonographic detection over 6 hours]. AB - A 75-year old female with chronic bronchitis and cor pulmonale was admitted because of massive pulmonary thromboembolism. Echocardiography showed a 9 cm embolus in the dilated right atrium changing in form and position. It was not fixed to the wall and was prolapsing and relapsing through the tricuspid valve. The tromboembolus was visible in the right heart for a period of at least 6 h. The patient survived without operation or fibrinolytic therapy. PMID- 3333625 TI - [Sonography of the small and large intestine--differential diagnosis of wall thickening]. AB - With the aid of a subtle examination technique using suitable ultrasonic equipment, it is possible to visualize small and large bowel wall changes. In a prospective study, 416 patients with small-bowel or large-bowel diseases, and 197 patients with no diseases affecting the intestinal tract were investigated. It was found that the wall thickness--as reflected in the thickness of the echo-poor outer ring - in the healthy bowel may measure up to 3 mm. A thickness of 4-5 mm must be considered borderline. A wall thickness of 6 mm or more is one of a number of morphological changes that signal intestinal disease. In 78.4% of the cases, the pathological finding was correctly described or correctly evaluated with respect to its biological significance with the aid of ultrasound. An accurate determination of the anatomical localization was possible in 92.3% of these cases. The ultrasonographic appearance of the various bowel diseases is not infrequently similar or even identical. Nevertheless, the detection of a pathological finding always makes it possible to narrow down the differential diagnosis. Ultrasonography is a suitable procedure for the detection and follow up of intestinal wall thickening, which represents an important patho morphological substrate of a number of intestinal diseases. Within the framework of small and large bowel diagnostic evaluation, it should be used alongside endoscopy and X-ray contrast examination. Ultrasound is not able to exclude possible bowel disease. PMID- 3333626 TI - [Endoscopy in the diagnosis and treatment of acute obstructive pancreatitis]. AB - Opie's theory that obstruction of the Ampulla of Vateri can be a significant factor in acute pancreatitis, is supported by various clinical observations. The significance of further pathogenetic factors such as anatomic variance of the duct systems, pressure differences, direction of flow and composition of secretions will have to be established in future studies. The ERCP plays an important role as a safe and sensitive diagnostic procedure. Therefore, ERC should be carried out in all suspected acute obstructive pancreatitis cases. The appropriate selection of patients employing clinical and laboratory criteria and other imaging procedures should, in the future, be defined more accurately. Presently, in proven ampullary obstruction we always perform immediate endoscopic therapy. However, the gallstone-induced obstructive pancreatitis usually has a good recovery course, even with conservative management. Therefore, clinical studies should prospectively direct us to those cases, in which the invasive endoscopic procedure should be limited, i.e. patients with expected serious courses. Diagnostic and therapeutic endoscopy does not increase the morbidity and mortality of the acute obstructive pancreatitis. Unlike the surgical approach, the endoscopic procedure is less invasive and is preferred by patients. PMID- 3333627 TI - [New developments in the area of echocardiography and Doppler cardiography]. AB - The noninvasive diagnostic in cardiology was substantially enriched in the past few years by the development and validation of echocardiography systems which enable a simultaneous presentation of cardiac structures and blood flow velocities. Thereby, informations with respect to congenital and valvular heart disease can be obtained that prerequisited cardiac catheterisation in the years before. The valuation of ventricular function and the diagnosis of myocardial ischemia was advanced by computerized echo image processing. PMID- 3333628 TI - Automated and routine liquid chromatographic analysis of antiepileptic drugs. AB - We describe an optimized automated liquid chromatographic method for simultaneous measurement of primidone, phenobarbitone, phenytoin, carbamazepine and clonazepam. A Waters Tri-Module automation system is used and it provides direct read-out of results after chromatography. A one-step extraction with ethyl acetate is used to extract the drugs from 100 microL serum samples. We use an isocratic mobile phase and monitor the column effluent at 210 nm. Drug levels as low as 5 mumol/L can be detected. The within-run CV's range from 1.4 to 2.7%, and the between-run CV's range from 5.2 to 6.1%. Analytical recovery is in the range from 94-108%. The method compares favourably with the enzyme multiple immunoassay technique for routine antiepileptic drugs monitoring, in accuracy, efficiency and cost-effectiveness. PMID- 3333629 TI - The efficacy of antimicrobial agents in periodontal therapy. PMID- 3333630 TI - Copper band impression--one step gingival tissue displacement and impression technique. PMID- 3333631 TI - Set-up of artificial teeth in abnormal jaw relationship. PMID- 3333633 TI - Corneal endothelium and penetrating keratoplasty. PMID- 3333632 TI - Alternative metal ceramic alloys. Part II: Base metal alloys. PMID- 3333634 TI - Intraocular lenses: changing indications. PMID- 3333635 TI - [The general development of Chinese ophthalmology]. PMID- 3333636 TI - Low vision related to function and rehabilitation. PMID- 3333638 TI - Surgical management of ocular trauma: penetrating injuries. PMID- 3333637 TI - Microsurgery of conjunctiva and Tenon's capsule. PMID- 3333639 TI - History of prevention of blindness in Japan. PMID- 3333640 TI - [Ultrasound and CT scanning in ocular lesions]. PMID- 3333641 TI - [Toxicological and analytical lists: chromium and its compounds]. AB - The main aspects of occupational exposure to chromium and chromium compounds are surveyed. Special attention is paid to the toxic action of this metal at the different target organs. The nutritional aspect of CrIII is examined preliminarily, and data detailing the metal contents in water and food are provided. As far the different working processes that entail occupational exposure to chromium are concerned, hygienic and environmental problems are discussed while identifying the average environment exposure to the different chemical forms of chromium (CrIII, CrIV, soluble and not soluble), as a function of the worker's tasks, and the relevant human response (total human Cr). Different hygienic and environmental standards in force in various countries and applicable to chromium compounds are compared. Additional information is given on the main aspects of chromium metabolism (absorption, distribution, excretion), and on the prevailing toxic actions, with specific reference to cancerogenesis. As far as biologic monitoring of the exposed people is concerned, the significance of Cr-U as dose-exposure indicator is discussed, also in the light of a critical review of the reference values. The report describes a series of analytical methods for the identification of chromium in aqueous and biologic matrices. The problems connected with health monitoring and fitness for work are eventually covered. PMID- 3333642 TI - Equine zona pellucida and capsule: some physicochemical and antigenic properties. AB - The capsule which surrounds the pre-attachment equine embryo has been compared with the zona pellucida (zp) that it replaces, as well as with the rabbit blastocyst coverings, by means of physicochemical and immunological methods. Trypsin solution at pH varying between 7.5 and 9.0 completely solubilized the capsule, as did Na borohydride. However, solutions of pH 2.0 or 12.0, urea, high temperature (65 degrees C, 60 min or 80 degrees C, 30 min), mercaptoethanol and dithiothreitol were able to solubilize the zp but not the capsule at the concentrations used. Indirect immunofluorescence on cryostat sections and whole mounts of fresh or frozen-thawed material showed that 1) common antigens are shared by equine, porcine and bovine zp; 2) day 7 to day 15.5 capsule reacted with anti-capsule-serum but not with anti-zp-serum except for a few patches on the surface of the capsule; 3) anti-capsule-serum, but not anti-zp-serum, reacted with the capsular material recovered along with a broken day 27.5 conceptus; 4) anti-capsule-serum does not react with rabbit blastocyst coverings; 5) anti capsule antibodies can be absorbed from the anti-capsule-serum by uterine proteins from either pregnant or non-pregnant mares; and 6) the capsule does not contain mouse laminin-like material. PMID- 3333643 TI - Features of a seminal proteinase inhibitor- zona pellucida-binding component on murine spermatozoa. AB - Murine cauda epididymal sperm contain sites on the plasma membrane over the apical portion of the acrosome that recognize proteinase inhibitors and the homologous zona pellucida. Ten times more of the component can be extracted from cauda and ductus sperm than from equal numbers of caput and corpus sperm. Likewise, few sperm from the upper epididymal regions are able to bind seminal inhibitor, while the majority of sperm from the cauda and ductus do bind. Cauda epididymal and ductus sperm lose little of their ability to bind inhibitor after a 4-hour in vitro incubation in either a capacitating or a noncapacitating medium. The percentage of naturally inseminated sperm with the seminal inhibitor bound to their surface decreases to about 10 after 4 hours in utero. Approximately 80% of these sperm show positive fluorescence when given the opportunity to rebind the the inhibitor, and these sperm do have an intact plasma membrane over the apical portion of the acrosome. Furthermore, after 4 hours in utero, the inhibitor bound in the same region of the sperm head as it did on freshly ejaculated sperm. The seminal inhibitor inhibits the binding of sperm to the zona if added during the first 15 minutes of incubation but has no effect on attachment. The data indicate that sperm gain the ability to bind the seminal inhibitor during the epididymal sojourn. Furthermore, this binding capacity is not lost during in vitro or in utero incubation. The site is not involved in sperm-zona attachment but does participate in the binding of sperm to the zona. PMID- 3333644 TI - Intramobile cylinder (IMZ) two-stage osteointegrated implant system with the intramobile element (IME): part I. Its ratinale and procedure for use. PMID- 3333646 TI - Mandibular reconstruction with autogenous and alloplastic materials following resection of an odontogenic myxoma. PMID- 3333645 TI - A small animal model for investigating endosseous dental implants: effect of graft materials on healing of endosseous, porous-surfaced implants placed in a fresh extraction socket. PMID- 3333647 TI - Dacryocystitis: bacteriological study and its relation with nasal pathology. PMID- 3333648 TI - Evaluation of oxymetazoline and naphazoline in benign red eyes: a double blind comparative clinical trial. PMID- 3333649 TI - Microbial contaminants of donor eyes and their antimicrobial sensitivity patterns. PMID- 3333650 TI - Paralimbal conjuntival incision in squint surgery. PMID- 3333651 TI - Ultrasound and root canal treatment: the need for scientific evaluation. PMID- 3333652 TI - [Retention of enamel-dentin adhesives. Visualization trial]. PMID- 3333653 TI - [Current knowledge of amalgam corrosion]. PMID- 3333654 TI - A critical review of the impact of insecticidal spray under NMEP on malaria situation in India. PMID- 3333655 TI - The natural history of bacteriuria in childhood. AB - The highest figure for first-time UTI is found in infants below one year of age. These early infections are often pyelonephritic in character, but they are easily overlooked because symptoms are unspecific, high fever and failure to thrive being the most important. It has been shown that delay in start of treatment increases the risk of the child developing pyelonephritic scarring. There is reason to believe that undetected and therefore untreated attacks of pyelonephritis may be associated with renal scarring revealed later in life. This type of renal damage is associated with development of hypertension in about 10 per cent of children and it accounts for around 20 per cent of the children entered into dialysis and transplant programs. Prevention of such long-term problems would be of great value and pyelonephritic scarring is a potentially preventable disease. The majority of infants and young children with UTI are probably managed at the primary care level. It is therefore essential that general practitioners are well informed about the epidemiology of UTI in infancy and childhood and that adequate diagnostic facilities are provided. For example, suprapubic aspiration to obtain uncontaminated urine is a technique that may well be used in an outpatient setting, and dipslide cultures are accurate and inexpensive. In addition to young age, vesicoureteric reflux and repeated attacks of pyelonephritis are risk factors associated with development of renal scarring. Therefore, diagnostic imaging to detect children with anomalies within the urinary tract are especially important in the very young. Furthermore, long-term supervision should be provided and the parents advised to consult the doctor when there is suspicion of a new infection to avoid delay in treatment. There is no reason to perform general screening for bacteriuria in healthy infants. Although bacteriuria may be found in 1 to 2 per cent, asymptomatic children have a very high rate of spontaneous clearing of the bacteriuria and they seem to constitute a low-risk group. Instead, frequent culturing of urine from febrile infants would be much more important. PMID- 3333656 TI - Bacterial virulence in urinary tract infection. AB - The severity of an infection is a function of the resistance of the host and the virulence of the infecting strain. Infections of the urinary tract can be caused by a wide range of gram-negative and gram-positive bacteria, which also are constituents of the normal flora. Indeed, most uropathogens originate from the intestinal tract. Still, the virulence concept implies that bacteria associated with urinary tract infections differ from members of the indigenous flora not causing infections. This review attempts to summarize the mechanisms known to contribute to bacterial virulence in the urinary tract and their relevance in different patient groups. PMID- 3333657 TI - Pathogenesis of urinary tract infections. Host defenses. AB - Host defenses in the urinary tract constitute a highly complex and efficient system of physical, chemical, genetic, and immunologic measures aimed at limiting the presence of bacteria in the urinary tract. These mechanisms vary in their roles at different anatomical levels and are directed at eliminating bacteria and preventing their ascent to the upper tract. A detailed description is provided of anticolonization and antiadherence mechanisms that may fail for a variety of congenital and acquired reasons. Major defects in host defenses such as obstruction, stasis, calculi, and diabetes are discussed together with the pathogenesis of urinary tract infection in adults with radiologically normal urinary tracts. PMID- 3333658 TI - Diagnosis and treatment of acute urinary tract infections. AB - Acute urinary tract infections are a major health problem in adult women. This discussion presents a practical approach to their diagnosis and treatment that incorporates recent research developments and that is designed to minimize the cost and adverse effects of therapy while maintaining therapeutic efficacy. PMID- 3333660 TI - Bacteriuria in pregnancy. AB - The urinary tract undergoes profound physiologic and anatomic changes during pregnancy that facilitate the development of symptomatic urinary tract infections in women with bacteriuria. While the adverse effects of asymptomatic bacteriuria on maternal and fetal health continue to be debated, it is clear that asymptomatic bacteriuria is the major risk factor for developing symptomatic urinary tract infection and that symptomatic infections are associated with significant maternal and fetal risks. Because the majority of symptomatic urinary tract infections develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy is as effective as prolonged therapy and should be followed with a repeat culture to document clearing of the bacteriuria. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a complete urologic evaluation after delivery. PMID- 3333659 TI - Recurrent urinary tract infection in adult women: diagnosis and treatment. AB - Recurrent urinary infection may be either relapse or reinfection. The majority of women experiencing recurrent infection have normal genitourinary tracts. For recurrent cystitis, single-dose therapy is optimal and symptomatic episodes are effectively prevented with continuous low-dose antimicrobial prophylaxis. For upper tract infection, or relapse after single dose therapy, two-week therapy is generally adequate. Investigation for abnormalities of the genitourinary tract should be reserved for women who fail to respond to therapy or with relapsing or bacteremic infection. PMID- 3333661 TI - Catheter-associated urinary tract infections. AB - The two most common indications for long-term catheterization are recalcitrant urinary incontinence and urinary obstruction that is not corrected by surgery. For incontinent patients, if behavioral changes, nursing care, special clothes, special bed clothes, and medications have not been successful, then a device to collect urine must be considered. For men such a device is a condom catheter; for women an analogous external collection device would be very useful. Suprapubic catheterization may offer an alternative but has been inadequately studied in this patient population. Long-term urinary catheterization has salutary effects for selected patients including patient comfort, family satisfaction, and nursing efficiency and effectiveness. To the patient for whom any physical movement is uncomfortable or painful, and indwelling catheter may be preferable to frequent changes of clothes. Similarly, the family of of severely impaired patients may want to accept the risks of urethral catheterization in order to keep the patient dry. Further, to the extent that the indwelling catheter is effective in decubitus ulcer prevention and/or management, long-term catheterization may diminish the risk of bacteremia or death from soft tissue infection. These benefits of long-term urethral catheterization, in addition to its risks, should be examined in future studies. Once a urethral catheter is in place, even with good catheter hygiene, bacterial entry can be postponed only temporarily; eventually all patients become bacteriuric. Indeed, as the catheter remains in place, organisms continue to enter, others leave or die, and the bacteriuria becomes complex, polymicrobial, and dynamic. Some organisms, particularly recognized uropathogens such as E. coli and K. pneumoniae, appear to reside in the urinary tract itself. Others, such as P. mirabilis, P. stuartii, and M. morganii, probably establish a niche within the urinary catheter, thus increasing their ability to cause subsequent bladder bacteriuria. The complications of long term urinary catheterization include fevers, acute pyelonephritis, and bacteremias (such as seen in short-term catheterized patients), as well as catheter obstructions, urinary stones, chronic renal inflammation, local periurinary infections, vasicoureteral reflux, renal failure, and, for very long term catheterized patients, bladder cancer. The thrust of catheter care for the long-term catheterized patient is to prevent complications of the omnipresent bacteriuria. Unfortunately, clinical opportunities for preventing complications are limited.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3333662 TI - Acute and chronic prostatitis: diagnosis and treatment. AB - Several distinct types of prostatitis, or prostatitis syndromes, are now recognized. The most common types include acute and chronic bacterial prostatitis, nonbacterial prostatitis, and prostatodynia. Bacterial prostatitis, caused mainly by enterobacteria, is often difficult to cure, and chronic bacterial prostatitis is a common cause of relapsing recurrent urinary tract infection in men. Nonbacterial prostatitis, the most common syndrome, is an inflammation of the prostate of unknown cause. Patients with prostatodynia typically have sterile cultures and normal prostatic secretions but demonstrate an acquired voiding dysfunction on video-urodynamic testing. Since nonbacterial types of prostatitis have no recognized infectious cause, treatment using antimicrobial agents is ineffective and unwarranted. PMID- 3333663 TI - Urinary tract infections in urology: a urologist's view of chronic bacteriuria. AB - Urine culture performed during and after antimicrobial therapy will differentiate unresolved urinary tract infections from recurrent infections. Recurrent infections with the same organism and at close intervals are frequently caused by a focus of bacterial persistence within the urinary tract, and infections with different organisms and/or at longer intervals are characteristic of reinfections with bacteria from outside the urinary tract. Unresolved infections are usually due to resistant bacteria and are treated by modification of therapy based on antimicrobial sensitivity testing. When unresolved bacteriuria is caused by organisms sensitive to the initial antimicrobial therapy, azotemia or a large bacterial mass density should be suspected. Recurrent infections at close intervals and/or with the same organism are usually caused by a bacterial focus in an acquired or congenital abnormality of the urinary tract such as infection stones, which must be removed to cure the recurrent infections. If the bacterial focus within the urinary tract cannot be removed, long-term low-dose antimicrobial prophylaxis can prevent the morbidity of recurrent infections. Reinfection requires careful bacteriologic monitoring and low-dose prophylactic, intermittent, or post-intercourse antimicrobial therapy. PMID- 3333664 TI - Asymptomatic bacteriuria in the elderly. AB - Bacteriuria in the elderly is common and usually asymptomatic. In the absence of symptoms and/or obstructive uropathy (which is rare in women), bacteriuria in the elderly appears to be a benign disease and therefore antimicrobial therapy is probably not warranted. PMID- 3333665 TI - Renal and perirenal abscesses. AB - Our knowledge of the spectrum of renal abscesses has increased as a result of more sensitive radiologic techniques. The classification of intrarenal abscess now includes acute focal bacterial nephritis and acute multifocal bacterial nephritis, as well as the previously recognized renal cortical abscess, renal corticomedullary abscess, and xanthogranulomatous pyelonephritis. In general, the clinical presentation of these entities does not differentiate them; various radiographic studies can distinguish them, however. The intrarenal abscess is usually treated successfully with antibiotic therapy alone. Antistaphylococcal therapy is indicated for the renal cortical abscess, whereas therapy directed against the common gram-negative uropathogens is indicated for most of the other entities. The perinephric abscess is often an elusive diagnosis, has a more serious prognosis, and is more difficult to treat. Drainage of the abscess and sometimes partial or complete nephrectomy are required for resolution. PMID- 3333666 TI - Contemporary imaging of renal inflammatory disease. AB - In addition to plain films and conventional excretory urography, ultrasound, computed tomography, and radionuclide scanning may contribute to the assessment of a wide spectrum of renal inflammatory diseases. This article discusses the role of contemporary imaging modalities in the diagnosis and management of patients with renal inflammatory lesions, including acute focal and diffuse bacterial infections, intra- and extrarenal abscess collections, pyonephrosis, xanthogranulomatous pyelonephritis, fungal infection, tuberculosis, and malakoplakia of the upper urinary tract. PMID- 3333667 TI - Chemical modification of polyurethanes by radiation-induced grafting. AB - Basic methods of radiation-induced modification of polyurethanes for biomedical applications and of their characterization are briefly described. The most important works found in literature on radiation grafting of polyurethanes are discussed. The radiation grafting of polyetherurethane films and tubings by the preswelling method using various monomers and their physico-chemical characterization are discussed in detail with respect to the antithrombogenic properties of the materials. Novel applications for radiation-modified polyurethanes as drug delivery systems or antiinfectious materials are briefly mentioned. PMID- 3333668 TI - Physical principles of ultrasonic imaging and Doppler blood flow analysis. PMID- 3333669 TI - [Development of ultrasonic image processing system for denture foundation by microcomputer]. PMID- 3333670 TI - [Basic study on laser welding of Ag-Pd-Cu-Au alloy. Part 1. Penetration depth and diameter of fusion zone]. PMID- 3333671 TI - [Laboratory-made stud attachment. Report II. Effect of cycle of engaging and disengaging on fatigue]. PMID- 3333672 TI - [The distribution of pressure on the denture supporting tissue and the possibility of determining the point of application of the biting force]. PMID- 3333674 TI - [The preparation for dowel-cores. Part 1. Convergency of three root canals of the mandibular first molar]. PMID- 3333675 TI - [The use of palatal training appliance in therapy of velar inadequacies]. PMID- 3333676 TI - [The design of resin-bonded bridges or splints with perforated retainers]. PMID- 3333673 TI - [The retention of cemented crowns. Part II. Influence of circumstance]. PMID- 3333677 TI - [Developments in oral and maxillofacial surgery in the past 2-3 decades at the University Hospital, Nijmegen, the Netherlands]. PMID- 3333679 TI - [Development in health care legislation in The Netherlands from 1865]. PMID- 3333678 TI - [Sensitivity for materials in resin dentures as a cause of the burning mouth syndrome]. PMID- 3333681 TI - Are adhesive techniques sufficient to prevent microleakage? PMID- 3333680 TI - [Gingival conditions in patients with fixed orthodontic appliances (multibond type and bonded brackets)]. PMID- 3333682 TI - [Mediation of abutment movement caused by extension denture clasps]. PMID- 3333683 TI - [Cervical adaptation of jacket crowns, using different construction technics]. PMID- 3333684 TI - [Behavior of Trypanosoma cruzi strains in agglutination reactions]. PMID- 3333685 TI - [Fixed prosthesis with removable gingiva]. PMID- 3333686 TI - [Adjunctive prostheses for OMF surgery and traumatology]. PMID- 3333688 TI - [Psycho-physical study on the dependence of seeing-light in determination of the color of dentures]. PMID- 3333687 TI - [Comparative clinical results in the treatment of gingivitis catarrhalis chronica with Furin M, applied by a tray for retention of the drug and by mouth rinsing]. PMID- 3333689 TI - [Functional studies on gingiva around the teeth, subject to orthodontic treatment]. PMID- 3333690 TI - [The teachers of the first Bulgarian dentists, graduates from Russia]. PMID- 3333691 TI - [Early Middle Ages medical compendium--the subject of the first doctor's historical-medical thesis in our country]. PMID- 3333692 TI - [The effect of a mineralizing agent on fissural enamel]. PMID- 3333693 TI - [Inhibition of C. albicans destructive action on dental surface by various drugs (experimental study in vitro)]. PMID- 3333695 TI - [Investigation of lymph nodes in maxillofacial region and neck by ultrasound tomography (echography)]. PMID- 3333694 TI - [Mathematical study on some harmful efforts of supporting teeth]. PMID- 3333696 TI - [Present state of dental implantology]. PMID- 3333697 TI - [Microbiological study on the tray for retaining a therapeutic agent on the mucosa of the oral cavity and periodontium]. PMID- 3333698 TI - [Combined express test for early (subclinical) diagnosis of gingival inflammation]. PMID- 3333699 TI - [Supporting frame for fixation of occlusal interaction]. PMID- 3333700 TI - [Orthopedic treatment of patient with pathologically low bite and prognathism]. PMID- 3333701 TI - [Effect of hydro-impulse therapy on gingiva of patients with hemorrhagic periodontosis (cytologic studies)]. PMID- 3333702 TI - Prosthetic replacement of the cranial cruciate ligament under arthroscopic guidance. A pilot project. AB - A prosthetic replacement for the cranial cruciate ligament was successfully implanted under arthroscopic guidance in four canine cadavers and seven normal dogs. Several strands of size 2 braided polyester were implanted in the cadavers and one normal dog, and a copolymer coated tow of 10,000 carbon fibers was implanted in six normal dogs. The average time required to surgically implant the carbon fiber prosthetic ligaments was 60 minutes. All of the dogs had slight to no drawer sign postoperatively. Five of the dogs were bearing more weight 3 weeks postoperatively than after transection of the cranial cruciate ligament. The surgical technique for implantation was successful for elimination of the cranial drawer sign, but carbon fibers were broken prematurely and instability reoccurred. PMID- 3333703 TI - Experimental large colon resection at the cecocolic ligament in the horse. AB - Ten normal horses had approximately 95% of the length of the large colon resected with a side-to-side anastomosis between right ventral and right dorsal colon performed with surgical stapling equipment. Four horses died shortly after surgery of colitis (1 horse) or failure of the TA 90 transection staple line (3 horses). Another horse died 4 months after surgery from disseminated streptococcal infection but had recovered well from the colon resection. Five horses survived long term (18 months) with no clinical evidence of adverse effects of the resection. Surviving horses had weight loss and soft fecal consistency for 3 to 12 weeks after surgery but returned to preoperative values within 12 months. At a second surgery 1 year later (5 horses) or at necropsy 4 months later (1 horse), fibrous omental adhesions were present over the transection staple line in four horses and over the anastomotic staple line in two horses. Omental adhesions to the everted staple line were moderate but not associated with any clinical sequellae. An incisional hernia was present in one horse. The anastomotic stomata measured between 8 and 9 cm, which was 60% of the size of the original surgically created stomata. Failure of the transection staple line occurred in the first three of five horses in which the procedure was attempted due to improper configuration of the staples or crushing of the tissue between the staples. Experience corrected this complication. PMID- 3333704 TI - Osteosarcoma at the site of a cortical bone allograft in a dog. AB - An osteosarcoma developed in the proximal femur of a 9-year-old female Great Dane. The femur had been fractured 5 years previously and was stabilized with plate fixation with the incorporation of a frozen cortical bone allograft. The dog recovered without complications after the surgery and had normal use of the leg before the osteosarcoma developed. The tumor had metastasized to the lungs, spleen, and ipsilateral popliteal lymph node. PMID- 3333705 TI - Evaluation of collagen as a retainer for autogenous cancellous bone used in repair of full thickness cortical bone defects. AB - A commercially available collagen sponge acting as a cylindrical retainer containing autogenous cancellous bone graft was proposed for treatment of full thickness cortical defects in dogs. Three groups of three dogs each were subjected to removal of at least 1.5 cm of the tibial diaphyses. All tibias were stabilized with bilateral external fixators. Group 1 received collagen surrounding an autogenous cancellous bone graft. Group 2 received collagen and group 3 received no treatment of the ostectomy site. The collagen sponge appeared to allow vascularization of the bone graft as evidenced by new bone formation and was resorbed by 3 months after implantation. Radiographic, histomorphologic, and histomorphometric evaluation at 3 months after surgery showed a greater per cent of bone in the ostectomy site in group 1. PMID- 3333706 TI - Immediate split-thickness autogenous skin grafts in the horse. Case reports on the treatment of equine sarcoids in 3 horses. AB - Three horses with equine sarcoids were treated with radical surgical excision and immediate split-thickness skin grafts. Graft take ranged from 50 to 100%, and the epithelial coverage attained resulted in an early functional repair. In no instance was there a recurrence of the sarcoid. PMID- 3333707 TI - Intrapelvic urethral anastomosis. A comparison of three techniques. AB - Three intrapelvic urethral anastomosis techniques were performed on 12 mature male dogs to compare the degree of stricture. The intrapelvic urethra was transected 1 cm caudal to the prostate, and anastomosis was performed using either suturing of the urethra over an indwelling catheter, suturing of the urethra without an indwelling catheter, or apposition of the urethra without sutures over an indwelling catheter. Postoperatively, the dogs were evaluated using clinical urination patterns, biochemical tests, radiography, and pathology. Three of four suture-catheter dogs and one of four catheter-only dogs had normal urinary patterns. Stricture (25-84%) with urethral dilation or fistulas tracts was visible on retrograde, positive contrast urethrograms of 3 of 12 intact dogs 20 weeks after surgery, and on all 12 excised lower urinary tracts. Suture catheter dogs subjectively had the least amount of stricture. All eight dogs (1 suture-catheter dog, 4 suture-only dogs, and 3 catheter-only dogs) with severe stricture (greater than 60% lumen diameter reduction) had histopathologic signs of chronic, inflammatory urinary tract disease, including four with chronic, ascending lymphocytic pyelonephritis. Hydroureter and hydronephrosis developed in two catheter-only dogs. Complete urethral transection resulted in some degree of stricture, regardless of technique used for anastomosis. Urethral anastomosis over an indwelling catheter appeared to result in a lesser degree of stricture and clinical and histopathologic derangement. PMID- 3333708 TI - Gastric drainage procedures: effects in normal dogs. I. Introduction and description of surgical procedures. AB - Gastric drainage procedures are commonly used in veterinary medicine, particularly in dogs in attempts to prevent recurrence of gastric dilatation volvulus (GDV). The following five different procedures have been most commonly described: the Fredet-Ramstedt pyloromyotomy (FRP); Heineke-Mikulicz pyloroplasty (HMP); Finney pyloroplasty (FP); Jaboulay's gastroduodenostomy (JG); and antral gastrojejunostomy (AG). These surgical procedures have not been compared in a controlled study. This first article of a series of three describes the gastric drainage procedures performed in 30 normal dogs for a comparative study. The FRP and HMP were the fastest and easiest procedures to perform. The degree of difficulty was found to be increased but similar for FP, JG, and AG. No complication occurred during or immediately after surgery. PMID- 3333709 TI - Preservation of skin by refrigeration for autogenous grafting in the horse. AB - Eighteen stored split thickness meshed skin grafts were applied to surgically created lesions on the metacarpal and metatarsal regions of six horses. Donor skin was harvested from the sternal region, meshed and stored at 4 degrees C in a cell culture medium containing 10% serum. Stored grafts were applied to the wounds at 1, 2, and 3 week intervals. Acceptance of the grafts stored for 1 week was generally poor (1 of 6 grafts), whereas that of the 2 and 3 week old grafts was generally excellent (10 of 12 grafts). Poor acceptance of the 1 week old grafts was attributed to streptococcal infection of the recipient wounds. Using the storage medium and grafting technique described, excellent acceptance can be expected after graft storage of up to 3 weeks. PMID- 3333710 TI - Use of intraoperative ultrasonography to identify a cervical foreign body. A case report. AB - Real-time ultrasound was used to identify a foreign-body abscess causing an extraluminal esophageal obstruction in the neck of a horse. Surgical exploration to remove the foreign body and drain the abscess was performed after 2 months of medical management that had failed to resolve the problem. The abscess could not be visualized because there was no draining tract or other localizing sign of inflammation. Ultrasound was used aseptically to guide surgical dissection to the walled off abscess with minimal damage to adjacent vital structures in the surgical field. The signs of esophageal obstruction abated and have not recurred in 15 months. PMID- 3333711 TI - Effect of ethylene oxide sterilization and storage conditions on canine cortical bone harvested for banking. AB - Two hundred seventeen cortical bones were harvested cleanly and prepared for banking for 2 months by using one of three types of packing materials, two ethylene oxide (EO) concentrations and procedures, and two storage temperatures. Bone subjected to the various treatments was compared to freshly harvested cortical bone and bone tested immediately after sterilization. Parameters evaluated were handling characteristics during preparation for and placement of a 3.5 mm cortex screw, and the percentage of weight lost as water when the bones were dried in an oven at 100 degrees C for 72 hours. Methods of sterilization, packaging material, and temperature of storage affected the handling characteristics and dehydration of the bone specimens. Twelve per cent EO at an elevated temperature and pressure, paper packaging, and room temperature storage appeared to cause the most significant changes. The use of 84% EO at room temperature and pressure, polyethylene wrapping material, and storage at -20 degrees C appeared to protect bone from dehydration. There was an increase in cracking and splitting of the bones as the percent of water loss decreased (indicating dehydration at the time of testing). Dehydration due to sterilization and storage processes may lead to difficulty in preparing bone for insertion of a bone screw and subsequently jeopardizing the stability of a repair in which such alloimplants are used. PMID- 3333712 TI - Anesthesia and cardiopulmonary bypass technique in calves and sheep. AB - The number of research institutions using calves and sheep as models for open heart surgical procedures is increasing. The Artificial Heart Laboratory of the University of Utah has developed an effective protocol for thoracic procedures in these animals. Routine barbiturate induction and maintenance with fluothane and a pressure-regulated ventilator have minimized anesthetic problems. A membrane oxygenator with blood flows of 50 to 75 ml/kg body weight/min. seems to give adequate circulatory support during heart-lung bypass. Although animals implanted with total artificial hearts do not have problems with arrhythmias, changes in pulmonary function and peripheral vascular tone can alter their cardiac performance. The judicious use of ventilatory support and specific vasoactive drugs can significantly improve the animal's intraoperative blood pressure and postoperative arterial gases. A summary of the techniques and drugs which were used successfully in 187 of 189 animals during a 2 year period are presented. PMID- 3333713 TI - Venous thromboembolism. PMID- 3333715 TI - Microvascular permeability in endotoxin and bacterial shock. PMID- 3333714 TI - Cardiorespiratory monitoring in the high-risk infant. PMID- 3333716 TI - Central venous catheterization. Indications, techniques, complications, management. PMID- 3333717 TI - [Periodontal prosthetic treatment. Report of a clinical case]. PMID- 3333718 TI - [Primary hyperparathyroidism. Report of a case with initial mandibular localization of the lesion]. PMID- 3333719 TI - [Carcinomas of the oral cavity: cancer of the floor of the mouth]. PMID- 3333720 TI - [Porcelain laminate veneers]. PMID- 3333722 TI - [Use of tissue bars in restorative dentistry]. PMID- 3333721 TI - [Exfoliative cytology in patients with periodontal disease]. PMID- 3333723 TI - [Cosmetic dentistry, another alternative]. PMID- 3333724 TI - Separation and studies of serum proteins with aid of aqueous two-phase systems containing dyes as affinity ligands. PMID- 3333725 TI - Improved HPLC determination of urinary neopterin. AB - In order to improve the urinary neopterin measurement, the reversed-phase HPLC method has been reevaluated. The parameters which influence the chromatographic behavior of 12 pteridines were studied: nature of buffer, pH, ionic strength, addition of organic modifier to the mobile phase. Accordingly, an isocratic HPLC method is described which offers a good compromise between specificity and analysis time. This method is well-suited to automation in routine clinical laboratory use. Using this HPLC method, urinary neopterin related to creatinine was determined in lung diseases (neoplasm, sarcoidosis and bronchial asthma) and in kidney allografts. This method was shown to be useful in the diagnosis and in the monitoring of treatment of rejection episodes. PMID- 3333726 TI - Development of a selective clean-up method using immobilized antibody and its application to HPLC and GC/MS determination of a carbacyclin derivative, CS-570, in plasma. AB - Methods for the determination of CS-570, a chemically stable prostacyclin analogue, in plasma were developed by using an immobilized antibody column followed by fluorescence HPLC and GC/MS. The CS-570 antibody, obtained from rabbit plasma by giving CS-570-BSA for a few months, was coupled to Sepharose 4B and used as extraction phase for sample clean-up and extraction of the drug. A plasma sample was applied to this column, washed with water and the drug was eluted with 90% acetonitrile. 0.02% (w/v) 9-anthryldiazomethane (ADAM) was added to the extract to form a fluorescent derivative. The CS-570-ADAM adduct exhibited high sensitivity when applied to HPLC with fluorescence detection and column switching. The detection limit was 1 ng/mL when 1 mL of plasma was available. Additionally, a pentafluorobenzyltrimethylsilyl derivative of CS-570 showed excellent sensitivity when determined by capillary GC interfaced to negative ion chemical ionization MS using a stable isotope labelled analogue as an internal standard. PMID- 3333727 TI - Purification of streptococcal protein G expressed by Escherichia coli by high performance liquid affinity chromatography using immobilized immunoglobulin G and albumin. AB - A one-step HPLC method was developed for the purification of protein G, a cell wall molecule from group C and G streptococci with immunoglobulin G- and albumin binding properties. Lysed Escherichia coli bacteria infected with lambda-phages containing the protein G gene from group G streptococci were used as a starting material for the preparations. The lysate was applied to a column with immobilized human immunoglobulin G or human serum albumin. Protein G was selectively bound and eluted at pH 2.0. A 750-fold purification was achieved. Sodium dodecylsulfate + polyacrylamide gel electrophoresis showed that the highly purified protein G consisted of three sets of doublets with the apparent molecular weight of 64 and 67, 56 and 58, and 45 and 47 kilodaltons, respectively. A specific method for quantitation of small amounts of protein G was developed and used for specific tracing of the protein after the affinity chromatography. Goat polyclonal antibodies were bound to an antigen coated to the plastic walls of microtiter plates, causing the Fc-region of the immunoglobulins to be directed outwards. Unknown samples of protein G were then allowed to compete with radio-iodinated protein G (solid phase radioassay) or protein G coupled to alkaline phosphatase (enzyme linked sorbent assay) for the Fc-regions. PMID- 3333729 TI - The elucidation of protein function from its amino acid sequence. AB - This review gives an outline of how computers may be used to determine the function of a protein, when only its primary structure is known. The current programming methods are outlined in general terms before their detailed application is discussed, and the common ways of predicting protein structure are also introduced. Identification is usually by database searching and sequence alignment, though a collection of motifs relating sequence to function are also described. PMID- 3333728 TI - Protein graphics: historical development, future directions and microcomputer applications. PMID- 3333730 TI - Microcomputer simulation of steady-state enzyme kinetics for educational purposes. AB - A BASIC program to assist the instruction of steady-state enzyme kinetics has been developed for the IBM PC microcomputer. Its purpose is to simulate laboratory experiments in order to minimize the time required to obtain kinetic data from which students deduce kinetic mechanisms and determine kinetic constants of enzyme-catalyzed reactions. The program randomly selects a kinetic scheme from various sequential, ping pong, and iso reaction sequences as well as values for the kinetic constants. The scheme and kinetic constants are unknown to the student at this time; the only thing he or she knows is the stoichiometry of the catalyzed reaction which can have two or three substrates and products. The student is prompted to enter values for concentrations of substrates and products; several different concentrations for each substrate and product can be entered in a single experiment. The program then calculates, displays and prints (if desired) the corresponding initial steady-state velocities. The student can perform as many experiments as desired until enough information is obtained to determine the kinetic mechanism and to calculate values for the kinetic constants. PMID- 3333731 TI - Mutagenicity, sister chromatid exchange inducibility and in vitro cell transforming ability of particulates from Athens air. AB - Airborne particulates were collected over a period of twelve months by the use of Hi-Vol samplers in the basin of Athens, Greece. N-Hexane extracts were tested in a battery of in vitro tests for their ability to induce mutation in bacteria as well as mutation, sister chromatid exchange and morphological transformation in cultured mammalian cells. Positive results were found for mutagenicity with Salmonella strain TA98 in the Ames assay, for sister chromatid exchange induction in CHO cells and for transformation in BALB/c 3T3 cells in culture. They also showed weak non-dose-related induction of ouabain resistance in BALB/c 3T3 cells. The contribution of oxidizing and nitrating agents found in the Athens atmosphere, together with sunlight UV irradiation in the formation of direct acting mutagens and potential carcinogens from ambient polycyclic aromatic hydrocarbons, is suggested. PMID- 3333733 TI - The genetic toxicity of 1,2-dibromo-3-chloropropane, 1,2-dibromo-3-chloro-2 methylpropane, and 1,2,3-tribromo-2-methylpropane. AB - 1,2-Dibromo-3-chloro-2-methylpropane (DBCMP) and 1,2,3-tribromo-2-methylpropane (TBMP) are contaminants formed during the manufacture of bromobutyl rubber. These chemicals are structurally similar to 1,2-dibromo-3-chloropropane (DBCP), a known genotoxin and rodent carcinogen. The present study compared the genotoxic properties of DBCMP and TBMP to those of DBCP. In the Salmonella assay, DBCP was positive in strains TA-98, TA-100 and TA-1535 in the presence of exogenous activation; DBCP was weakly active in TA-1535 in the absence of activation. Neither DBCMP nor TBMP produced reproducible evidence of mutagenic activity in the Salmonella assay despite the use of several different variations of this test. In the mouse lymphoma gene mutation assay, DBCP and TBMP were positive in the presence and absence of activation, while DBCMP was positive only in the absence of activation. All three test compounds were active in the Syrian hamster embryo morphologic transformation assay. The results indicated that both DBCMP and TBMP exhibited some genotoxic activity as did DBCP. The presence of the methyl group on the 2-carbon position essentially eliminated the mutagenicity of DBCMP and TBMP in the Salmonella assay. PMID- 3333732 TI - Species variation in bladder cell and liver cell activation of acetylaminofluorene. AB - The metabolism and mutagenicity of 2-acetylaminofluorene were measured using freshly prepared intact bladder and liver cells from the cow, dog and rat. High pressure liquid chromatography was used to separate 2-acetylaminofluorene metabolites, and Salmonella typhimurium, strain TA98, was used to detect mutagenic intermediates. Species differences as well as animal-to-animal variation within a species were observed. Mutagenic activity with 2 acetylaminofluorene was greater with cow bladder cells than with dog or rat bladder cells. However, dog bladder cells were most active in metabolizing 2 acetylaminofluorene, and rat bladder cells were least active. Liver cells from all three species metabolized 2-acetylaminofluorene to mutagens for Salmonella, with dog and cow cells being more active than rat liver cells. However, cow liver cells were the most active in metabolizing 2-acetylaminofluorene, followed by rat and dog cells. With all cell types studied, except rat bladder cells, aminofluorene was the major metabolite detected. Carbon and N-hydroxylated products were produced by liver and bladder cells of the three species and glucuronide and sulfate conjugates of the metabolites were detected from both cell types. Correlations between mutagenic activity and the level of metabolism or any individual metabolite were not apparent. The data suggest that the relative contribution of bladder cell metabolism in aromatic amine induced bladder cancer may vary with the species. PMID- 3333735 TI - [To professor A. Gerber on his 80th birthday. His articulator and his condylar theory: a modern and current reality]. PMID- 3333734 TI - Modification of the cell surface expression of histocompatibility antigens induced by the neurotoxin 2,5 hexanedione. AB - Class I histocompatibility antigens (HLA) are expressed on the surface of almost all nucleated mammalian cells; the expression of this surface antigenic molecule may be changed or abrogated by several factors. In this paper, a modification in HLA expression in a human carcinoma cell line following exposure to the neurotoxicant 2,5 hexanedione is reported. This compound is known to produce a wide spectrum of subcellular pathological events; in this study, we describe an effect on the surface and cytoplasmic distribution of both light and heavy subunits of HLA antigens, demonstrated by immunocytochemical and immunoelectron microscopy techniques. Human carcinoma cells, which under normal growing conditions express the HLA, abrogate the surface expression of this glycoprotein after exposure to 2,5 hexanedione and an intracytoplasmic accumulation seems to occur. Several possibilities are discussed, such as an effect of the toxicant on the transport of the nascent glycoprotein. PMID- 3333736 TI - [Dimensional variations in alginate impressions]. PMID- 3333737 TI - [The Reval casting technic]. PMID- 3333738 TI - [The choice of mandibulo-maxillary relations in prosthodontics]. PMID- 3333739 TI - [Acrylic denture bases. Demonstration of the role of plaster in reduction of the palatal hiatus]. PMID- 3333740 TI - [Endo-occluso-periodontal temporization in 1987]. PMID- 3333741 TI - The biotechnology of Bacillus thuringiensis. AB - One of the challenges in the application of biotechnology to pest control is the identification of agents found in nature which can be used effectively. Biotechnology offers the potential of developing pesticides based on such agents which will provide environmentally sound and economically feasible insect control alternatives. Such an agent, the insect pathogen Bacillus thuringiensis, is the subject of intense investigations in several laboratories. Insecticides which use the entomocidal properties of B. thuringiensis are currently produced and sold worldwide; new products are currently in the development stage. Herein, the biology and genetics of B. thuringiensis and the problems associated with current products are critically reviewed with respect to biotechnology. Moreover, the economic and regulatory implications of technologically advanced products are evaluated. PMID- 3333744 TI - [Relationship between harmful environmental factors at the working place and oral mucosa diseases in workers in certain divisions of a furniture factory]. PMID- 3333745 TI - [Radiological diagnosis of dental caries. Present state and perspectives of development]. PMID- 3333742 TI - Swallowing: neurophysiologic control of the esophageal phase. PMID- 3333746 TI - [The course of orthodontic treatment in selected cases with extraction of permanent teeth]. PMID- 3333743 TI - A rational clinical approach to esophageal motor disorders. PMID- 3333747 TI - A comparative scanning electron microscope study of acid etch technique of "normal" American, "normal" Kenyan and fluorosed Kenyan teeth. PMID- 3333748 TI - Eleven years of follow-up of the pattern of leprosy complications at Alupe Leprosy Hospital. PMID- 3333750 TI - [Furcation invasions: etiology and treatment. Review of the literature]. PMID- 3333749 TI - [Mercury--fetotoxic effects]. PMID- 3333751 TI - [Orthodontic movement]. PMID- 3333752 TI - Cleft lip and palate, seldom seen features of the Gorlin-Goltz syndrome. PMID- 3333753 TI - Dysbaric osteonecrosis (caisson disease of bone): are active oxygen species and the endocrine system responsible, and can control of the production of free radicals and their reaction products confer protection? AB - The development of osteonecrosis after exposure to altered air pressures is consistent with cellular injury brought about by active oxygen species. The syndrome is considered to arise as a result of an unusual combination of circumstances in which hyperoxia itself, together with the additive responses of the endocrine system to hyperoxia, hypothermia and exertion, each appear to play a part; the net result is thought to increase the mitochondrial generation of superoxide. It is suggested that effective prophylaxis may be possible primarily by establishing a nutritional status that is adequate to ensure that the functional activities of radical-scavenging systems are not hampered by deficiencies either of essential trace elements or of vitamin E. Pharmacological pretreatments designed both to decrease excessive levels of superoxide through increased catalysis of anionic dismutation and to attenuate enzyme-dependent peroxidation may provide an additional line of defence. PMID- 3333754 TI - Boar sperm surface glycoproteins: isolation, localization, and temporal expression during spermatogenesis. AB - Boar sperm glycoprotein fractions were isolated by Lens culinaris hemagglutinin affinity chromatography of detergent-solubilized ejaculated spermatozoa, followed by preparative sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. In order to develop methods for further investigations of the sperm proteins, we proceeded with two of the isolated glycoproteins. Antibodies were raised in female rabbits against each of the two sperm glycoproteins. By a combination of immunosorbent chromatography, using the antibodies obtained, and preparative SDS polyacrylamide gel electrophoresis, highly purified sperm proteins were isolated. The sperm proteins were immobilized on Sepharose gel columns and specific immunoglobulin Fab fragments were enriched by affinity chromatography. The specificity of the Fab fragments was ascertained by immunoprecipitation analysis. The Fab fragments were used in indirect immunofluorescence analysis to localize the corresponding antigens on the surface of boar spermatozoa. Both antigens were exclusively confined to the postacrosomal region. Immunohistochemical staining of boar testis sections revealed that both antigens are expressed from the spermatid stage. This technique also revealed that one of the antigens congregated at the Golgi complex-acrosome region during spermatogenesis. PMID- 3333755 TI - Actin and calmodulin coexist in the equatorial segment of ejaculated boar sperm. AB - The direct overlay technique with iodinated calmodulin on boar sperm fractions evidenced a strong bond in the 45,000 molecular weight, which is the region recognized by anti-actin antibodies. This result and the close codistribution of the two staining patterns for calmodulin and actin with immunofluorescence and immunoelectronmicroscopy suggest a possible interaction between calmodulin and actin in boar sperm. PMID- 3333756 TI - Phagocytosis of yeast by human oocytes: fine structural observations. AB - Fine-structure observations have been made on the interaction between invasive yeast cells and human oocytes. The yeast appear to make their way through the zona pellucida and once in the perivitelline space are incorporated into phagocytic vacuoles by surface activity of the oocyte. The yeast attach to the vitelline membrane via fuzzy surface material on the cell wall, and incorporation appears to be aided by oocyte microvillar activity. Coated pits in the oocyte plasma membrane are incorporated into the phagosomes, but no lysosomal activity is seen, and neither oocytes nor yeast cells appear to undergo degeneration in the time frame investigated. PMID- 3333757 TI - Visualization and characterization of the acrosome reaction of human spermatozoa by immunolocalization with monoclonal antibody. AB - A monoclonal antibody generated against hamster epididymal spermatozoa and recognizing an antigen within the acrosome was used in conjunction with FITC antimouse immunoglobulin as a marker of the human acrosome during sperm development, capacitation, and the acrosome reaction. The specificity of binding of the monoclonal antibody was assessed using immunolocalization by epi fluorescence and electron microscopy. Immunofluorescence revealed that antibody bound over the entire anterior acrosome in hamster and human spermatozoa. Ultrastructural localization indicated that antigen was predominantly present on the inner face of the outer acrosomal membrane and within the acrosomal content. Qualitative specificity was studied using a highly purified preparation of hamster acrosomes in an enzyme-linked immunosorbent assay. Since the antibody rapidly visualized human acrosomes, it was used to detect abnormal acrosome morphology of mature spermatozoa and to mark spermatids present in the ejaculate. During incubation in capacitating medium, changes in the immunofluorescence of live or methanol fixed spermatozoa were correlated with incubation interval and the ability of spermatozoa to fuse with zona-free hamster oocytes. Spermatozoa bound to zona-free hamster oocytes displayed no fluorescence, confirming that acrosome loss occurred before spermatozoa attached to the vitellus. PMID- 3333758 TI - Membrane molecules involved in adhesion properties of cultured Sertoli cells. AB - Membrane components involved in adhesion properties of cultured Sertoli cells have been studied by a combination of immunological and biochemical methods. An antiserum prepared against Sertoli cells induced reversible rounding and detachment of the cells from the culture dishes. The cell surface morphology during detachment was studied by scanning electron microscopy and indirect immunofluorescence. A Triton soluble fraction of crude membrane preparations inhibited the antibody-induced detachment. The antibodies recognized a restricted number of membrane glycoproteins [detectable as prominent bands on Sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), Mr 170, 140, 80, and 48K] both in the Triton soluble fraction of crude membrane preparation and on intact Sertoli cells. The data suggest that the molecules involved in adhesion properties of cultured Sertoli cells are integral membrane glycoproteins exposing antigenic determinants at the cell surface. PMID- 3333759 TI - Preparation of large numbers of plasmid DNA samples in microtiter plates by the alkaline lysis method. AB - A protocol is described for the growth and preparation of plasmid DNAs from small culture volumes (250 microliters) and utilizing standard 96-well plates. Several hundred plasmids can be prepared simultaneously, yielding sufficient DNA for subsequent analysis by restriction digestion and gel electrophoresis. This protocol may be useful for rapid screening of clones arising in recombinant DNA work such as site-directed mutagenesis, oligonucleotide cassette cloning, deletion analysis, etc. The technique was initially developed to meet our requirement to provide large numbers of cosmid DNAs for restriction enzyme fingerprint analyses in genome mapping projects. PMID- 3333760 TI - Distance analysis helps to establish characteristic motifs in intron sequences. AB - Computer-assisted sequence analysis was applied to detect the most apparent nonrandom sequence motifs in eukaryotic introns. We describe in detail a method, which we call distance analysis, that we applied to the extensive study of 405 eukaryotic intron sequences. We observed very strong two-base periodicities for almost all tetranucleotides that are tandem repeats of nonhomopolymeric dinucleotides (the exception was GCGC and CGCG). We also observed, by using a fixed-point alignment method, that these periodic sequence motifs belong to large clusters of dinucleotides repeated tandemly as many as 15-35 times, which corresponds to the cluster lengths of 30-70 bases. We did not observe two-base periodicity of tetranucleotides in the collections of either 262 spliced eukaryotic exons or 107 bacterial genes. Instead, these sequences displayed strong three-base periodicity of some other tetranucleotides. These findings suggest that introns and exons display distinct sequence properties that can be used for mapping purposes. PMID- 3333761 TI - A method for the preparation of high molecular weight yeast DNA. AB - A method is described for the isolation of high molecular weight DNA in solution using the principles that have allowed electrophoresis of chromosome-sized DNA in pulse field gradient electrophoresis. Stationary phase yeast cells are converted to spheroplasts by the action of zymolyase in 1 M sorbitol. In the presence of EDTA and sodium lauroyl sarcosinate, proteins are digested with proteinase K. DNA is extracted with phenol and chloroform, and high molecular weight DNA is collected by ethanol precipitation. RNA is removed by RNase digestion of the redissolved pellet, and RNase is removed by chloroform extraction followed by a second ethanol precipitation. The method is rapid and gives a high yield of DNA that is readily digestible by restriction endonucleases. PMID- 3333762 TI - Comparison and optimization of in situ hybridization procedures yielding rapid, sensitive mRNA detections. AB - This paper describes methods that are commonly used for performing mRNA in situ hybridizations. Each stage of the procedure has been analyzed to identify the parameters that most significantly affect the final cell morphology and sensitivity of the system. We have identified key elements of the procedure as the fixation employed, the type of polynucleotide probe and label chosen, and the detection system used. By optimizing these critical components, we have developed a procedure for performing mRNA in situ hybridizations that takes 2-4 hours and has a sensitivity of 1-10 molecules of mRNA per cell. This system has been used to detect levels of oncogene expression in normal bone marrow and peripheral blood. It is possible to detect the expression of three oncogenes (c-myc, c-sis, and c-abl) simultaneously in a small population of cells from the peripheral blood of leukemic patients. PMID- 3333764 TI - Factors influencing wound infection: time lapse analysis and wound culture studies. PMID- 3333763 TI - Induction of multiple replacement mutations by oligonucleotide-directed mutagenesis with extended mismatch primers. AB - We have developed a method called oligo-scanning mutagenesis that uses oligonucleotides to mutate up to 12 contiguous bases in a single step. Some advantages of this procedure are that the position and sequence of the replacement mutations are completely specified by the investigator, and combinations of mutations can easily be generated. The technique uses a gapped substrate and the Escherichia coli dam methylation error-correcting mechanism to increase the yield of mutants. PMID- 3333765 TI - Asymptomatic bacteriuria in school children: incidence and characterisation of invading organisms. PMID- 3333766 TI - Colour preservation and restoration in gross specimens. PMID- 3333767 TI - Ultrasonography in ocular trauma. PMID- 3333769 TI - Clinical features, including haemolytic-uraemic syndrome, in Shigella dysenteriae type 1 infection in children of Rangoon. PMID- 3333768 TI - Proto-chemotherapy in advanced head and neck cancer. AB - Induction (proto) chemotherapy consisting of 3 courses of cisplatin and 120-hour 5-fluorouracil infusion was administered to 88 patients who had locally advanced, previously untreated head and neck cancer. The majority (81%) of these patients were classified as stage IV, and 17% had second primary carcinomas of the upper aerodigestive tract. An overall response rate of 94% was observed, with a 54% incidence of complete clinical response. The toxicity of the chemotherapy was judged acceptable, and no life-threatening or fatal drug-related side effects occurred. Twenty-four percent of the patients failed to comply with recommended standard treatment. In patients achieving a complete clinical response, 47% refused recommended surgery. Any response less than a complete clinical response to induction chemotherapy was not associated with any survival advantage. We conclude that future research efforts should be directed toward the identification of chemotherapeutic regimins that maximize the incidence of complete clinical response. In addition, any large-scale chemotherapy trial in patients with resectable disease should avoid the use of an induction sequence to minimize compliance problems with standard treatment. PMID- 3333771 TI - Evolution of treatment of dehydrating diarrheas over the last quarter century. Introduction. PMID- 3333770 TI - Clinical trial of high-dose berberine and tetracycline in cholera. PMID- 3333772 TI - A history of the development of oral rehydration therapy (ORT). PMID- 3333773 TI - Selected bibliography: cereal based oral rehydration therapy. PMID- 3333774 TI - Prophylactic effect of diethylcarbamazine on W. bancrofti filariasis. PMID- 3333775 TI - Control of bancroftian filariasis in a rural area through selected treatment with diethylcarbamazine. PMID- 3333776 TI - Visceral leishmaniasis in India--a brief review. PMID- 3333777 TI - Outbreak of dysentery due to Shigella flexneri type 2a. PMID- 3333778 TI - Laboratory parameters in early and late cases of bancroftian filariasis in an endemic area. PMID- 3333779 TI - T cell factors involved in the isotype-specific regulation of the IgE antibody response. PMID- 3333780 TI - The IgE antibody response to the phosphorylcholine hapten. AB - The immune response to the phosphorylcholine (PC) hapten elicited by PC-keyhole limpet hemocyanin (KLH) is composed of 2 groups of antibodies with specificity to either PC or phenylphosphorylcholine which were designated as group I and II anti PC antibodies, respectively. We demonstrate that anti-PC IgE antibody expression is restricted to group II antibodies and does not display the T15 idiotype. Accordingly anti-PC IgE antibodies recognize the same epitope (PC-phenyl) as IgG1, IgG2a and IgG2b antibodies which is different from that (PC) recognized by IgM and IgG3 antibodies. A monoclonal anti-PC IgE antibody, representing group II characteristics was established. From amino acid sequences of light chains of purified group I and II antibodies from serum as well as of monoclonal representatives thereof it appears that both populations are relatively homogenous and represent independent clonal expressions. Nevertheless the formation of anti-PC IgE antibodies in mice can be suppressed by isologous anti T15 anti-idiotypic antiserum. This antiserum, however, crossreacts with different anti-PC antibodies including monoclonal group II anti-PC IgE antibodies and is composed of a large number of anti-idiotopes. An analyses performed with monoclonal anti-T15 idiotopes demonstrates that some but not all antibodies suppress the formation of anti-PC IgE. We conclude that syngeneically induced anti-idiotypic interactions may display regulation of a wide range of specificities affecting responses to various antigenic determinants. PMID- 3333781 TI - The isotypic circuit: immunoglobulins, Fc receptors and immunoglobulin binding factors. PMID- 3333782 TI - B lymphocyte progenitors in mouse bone marrow. PMID- 3333783 TI - Some facts about the progenitors of murine B lymphocytes. PMID- 3333784 TI - Long-term culture systems for analysis of early B lymphocyte development. PMID- 3333785 TI - Repertoire expression in surface immunoglobulin-negative bone marrow B cell precursors. PMID- 3333787 TI - [Castable apatite ceramics laminate veneers]. PMID- 3333786 TI - Bone marrow pre-B cells and the clonal anergy theory of immunologic tolerance. AB - This review begins with a summary of a decade's research from the author's own laboratory which documents the fact that B lymphocytes can receive and store negative, down-regulatory signals from an encounter with antigen, and that the sensitivity to such negative signalling depends critically on maturational status, the most immature B cells being the most susceptible. The review then examines the relationship between these experimentally-induced models of immunologic tolerance, with the pre-B to B cell transition as the critical stage for examination, and the real-life phenomenon of self-tolerance. It makes the point that no repertoire-purging mechanism to ensure self-tolerance can afford to be too effective, for fear of purging too many useful cells, given the number and variability of self-antigens. The review then examines certain dilemmas posed by recent findings in cellular and molecular immunology. These include: 1) the preferential use of particular VH gene families by B cells at different stages of the differentiation process; 2) the apparent frequency of B lymphocytes with the potential for antiself-reactivity in the B cell repertoire; and 3) the existence of a new type of B cell, the Ly-1-positive B cell, with peculiar characteristics. These findings are considered within the particular contexts of pre-B-to-B cell transition and tolerance induction through clonal anergy mechanisms. PMID- 3333788 TI - [A clinical study on the hemostatic effect of epinephrine]. PMID- 3333789 TI - First record of malaria and associated Anopheles in El Gara Oasis, Egypt. PMID- 3333790 TI - Anopheles population dynamics in two malaria endemic villages in Faiyum Governorate, Egypt. AB - Anopheles populations were monitored for one year in 2 neighboring villages in Faiyum Governorate, Egypt, to study factors causing differences in malaria prevalence. Both villages contained the following species: Anopheles pharoensis, An. sergentii, An. multicolor and An. tenebrosus. Abundant larval breeding sites in Abheet, the village with the higher malaria rate, accounted for the higher adult densities observed from human and animal biting collections and from indoor resting collections. Anopheles pharoensis and An. sergentii were the dominant species in Abheet with seasonal biting activity extending from May to December, reaching a peak in November. In El Zawya, the village with the lower malaria rate, An. pharoensis dominated, reaching seasonal peaks in June and August. Inside houses, An. sergentii was common from May to January in Abheet, but rare in El Zawya. Anopheles pharoensis and An. sergentii were both incriminated as malaria vectors based upon their seasonal abundance and the finding of sporozoite positive specimens during the peak malaria season. PMID- 3333791 TI - Aedes albopictus and arboviruses: a concise review of the literature. AB - Aedes albopictus is an efficient vector of the four dengue viruses, and it is also capable of transovarially transmitting these viruses. Aedes albopictus can also serve as a host and/or vector of several additional arboviruses, some of which are of considerable medical or veterinary importance. This review compiles previously published studies that have demonstrated an experimental or natural association between Ae. albopictus and specific arboviruses. PMID- 3333793 TI - Intravenous immunoglobulin for prophylaxis or treatment of bacterial infection in neonates. AB - The high rate of bacterial infection in premature neonates has been correlated with low levels of opsonic antibody. Infants born at term who develop a bacterial infection generally have very low levels of antibody toward the organisms with which they are infected. In order to provide adequate levels of antibacterial antibody to neonates, several strategies have been devised and tested. In this report, studies on animal investigations and clinical trials are reviewed. PMID- 3333794 TI - Alternative complement pathway activation by Salmonella O polysaccharide as a virulence determinant in the mouse. AB - The quality of Salmonella O polysaccharide (the O antigen) is a virulence factor in mouse salmonellosis. It affects the rate by which these bacteria are phagocytosed and by which they activate the alternative complement pathway in a manner inversely proportional to their virulence, suggesting that the rate of complement activation is crucial for the fate of the bacteria in the mouse. The effector mechanism has, however, remained open since Salmonellae survive and multiply in the macrophages of the mouse. We show in this study that although the least virulent O-6,7 Salmonellae multiply in the liver macrophages they are rapidly killed in the peritoneal cavity by the local resident macrophages. Electron microscopy showed a striking morphological feature--a 35 nm thick homogenous electron-dense deposit--on all the bacteria found in association with the macrophages but absent from all non-cell-associated bacteria. A similar precipitate was formed by incubating the bacteria in fresh mouse serum and was dependent on heat-labile serum components and bound anti-C3. The least virulent O 6,7 bacteria acquired this deposit more rapidly and in a lower concentration of serum than the more virulent O-4,12 bacteria consistent with the previously demonstrated difference between these bacteria in their rate of complement activation via the alternative pathway. Preincubation of the O-4,12 bacteria in fresh mouse serum leading to complement deposition on 80% of the bacteria effectively opsonized them for rapid killing in the peritoneal cavity. These data for the first time demonstrate how the rate of complement activation determines the virulence of Salmonellae. PMID- 3333792 TI - Genetics of Aedes albopictus. AB - Aedes albopictus is an important vector of dengue fever and dengue hemorrhagic fever in Southeast Asia. Its distribution extends from Madagascar to Hawaii and is currently expanding. From its proposed origin in Southeast Asia, Ae. albopictus has migrated as far as Mauritius and Madagascar to the west and Korea, Japan, Guam, Hawaii and other Pacific Islands to the east. In the continental United States, it was originally reported in the Texas area in August 1985 and is now well established in several states. This paper reviews information on distribution, cytology and genetics of Aedes albopictus. In addition, it includes comments on its competitive interaction with several other species. Relevant information on evolutionary genetics of certain other related sibling species is also included for comparative purposes. PMID- 3333795 TI - Characterisation of protein co-extracted together with LPS in Escherichia coli, Salmonella minnesota and Yersinia enterocolitica. AB - The porin proteins of Escherichia coli, Yersinia enterocolitica, and Salmonella minnesota were found to co-extract by the phenol-chloroform-petroleum ether method together with the R lipopolysaccharide of these strains. Lipopolysaccharide free protein recovered from the phenolic residue of the phenol chloroform-petroleum ether extract migrated as a Mr 36-37,000 protein. We could demonstrate that the protein was extracted from bacteria as a high molecular weight protein-lipopolysaccharide complex. Once exposed to phenolic conditions, the protein was no longer soluble in the phenol-chloroform-petroleum ether extraction mixture, indicating a highly specific lipopolysaccharide-protein association. PMID- 3333797 TI - Cloning and expression of a common Legionella outer membrane antigen in Escherichia coli. AB - A genomic library of Legionella pneumophila was constructed by inserting L. pneumophila knoxville-1 strain (LPK-1) chromosome fragments into cosmid vector pHC79. Screening of the library with antibodies directed against a major outer membrane protein/lipopolysaccharide complex from LPK-1 resulted in the identification of six clones that reacted with the antiserum. Western blot analysis indicated that a 19,000 dalton (19 kDa) component was the reactive antigen in all of the clones. Western blot analysis of outer membranes from L. pneumophila serogroups and other Legionella species revealed that the cloned 19 kDa antigen was common to all serogroups and all but one of the five other Legionella species examined. One of the 19 kDa expressing clones was used as an immunoabsorbent to recover antibody to the 19 kDa antigen thus confirming the surface localization of this L. pneumophila antigen in E. coli. PMID- 3333796 TI - Nucleotide sequence analysis of the structural genes for Shiga-like toxin I encoded by bacteriophage 933J from Escherichia coli. AB - A nucleotide sequence analysis was performed on the Shiga-like toxin I genes previously cloned from the Escherichia coli bacteriophage 933J. Two structural genes designated slt-I A and slt-I B were found to be oriented on a single transcriptional unit with slt-I A preceding slt-I B. A 12 base pair gap separated the in-phase open reading frames of slt-I A and slt-I B. Putative ribosome binding sites were identified 5' to both the slt-I A and slt-I B genes. Translation of the SLT-I nucleotide sequence revealed that both the A and B subunits were synthesized with signal peptides. The molecular weight calculated for the mature A subunit was 32,211 while the molecular weight of the mature B subunit was 7690. PMID- 3333799 TI - Salmonella typhimurium aroA mutants as carriers of the Escherichia coli heat labile enterotoxin B subunit to the murine secretory and systemic immune systems. AB - We investigated the ability of Salmonella typhimurium vaccines to deliver heterologous antigens to the systemic and secretory immune systems of the mouse, while retaining their immunogenicity against salmonellosis. S. typhimurium SL3261, an avirulent aroA mutant, or SL3261 carrying plasmid pBRD026, a pBR322 derivative encoding the gene for Escherichia coli LT-B were used to immunize BALB/c mice orally. Both immunizing strains invaded the mononuclear phagocyte system of the mice, grew slowly until approximately day 14 post-infection, and then were rapidly cleared. No salmonellae were detected in livers, spleens, mesenteric lymph nodes or Peyer's patches by day 42. Mice immunized with either strain and challenged orally with the virulent parent strain, SL1344, several weeks after clearing the immunizing organism, were protected against the lethal S. typhimurium infection. Mice infected with SL3261 (pBRD026) developed substantial levels of IgG and IgA anti-LT-B antibodies 14 days post-infection in both serum and gut samples. The sera neutralized the effects of LT in an in vitro Vero cell assay. Thus, aroA mutants of S. typhimurium can deliver a heterologous antigen from a different enteric pathogen to the murine systemic and secretory immune systems without altering their efficacy against salmonellosis. PMID- 3333798 TI - Probing the surface of bacteria: use of gold sphere immunological probes. PMID- 3333800 TI - Developing a human malaria sporozoite vaccine. PMID- 3333801 TI - The initial suppression of bacterial growth in a salmonella infection is mediated by a localized rather than a systemic response. AB - Mice were infected intravenously with two antibiotic resistance tagged variants of the same S. typhimurium strain given in close succession, or simultaneously with strains of different virulence. The first manifestation of acquired resistance--suppression of exponential bacterial growth in liver and spleen- occurred independently for the different strains in the same individuals, implying that it is due to localized rather than systemic events. This early suppression of bacterial growth was ablated by whole body X-irradiation (800R), whereas the immediately preceding phase of exponential growth (Ity controlled innate resistance) was not affected. Transfer of spleen cell suspensions from infected mice into syngeneic recipients conferred protection by suppressing the growth of an intravenous challenge. Pre-treatment of the suspensions to deplete them of macrophages abolished their protective capacity, while depletion of T cells did not. Mice deficient in T-cells by adult thymectomy and anti-T-cell monoclonal antibody treatment were able to suppress the growth of an intravenous challenge. Taken collectively, the present data show that the very early phase of acquired resistance to salmonellae, essential for survival, is not the result of systemically developing resistance but a localized event at the site of infection. PMID- 3333802 TI - Serotyping and genotyping of encapsulated Escherichia coli K1 sepsis isolates with a monoclonal IgG anti K1 antibody and K1 gene probes. AB - Among infectious diseases caused by E. coli the capsular type K1 plays a predominant role. E. coli K1 isolates account for 80% of cases of E. coli neonatal meningitis and 30% of E. coli sepsis strains. Serotyping of K1 strains has conventionally relied upon the use of K1-specific bacteriophages or serum agar methods with polyvalent anti K1 serum. In the study present here, 187 E. coli sepsis isolates have been analysed for production of the K1 antigen using K1 phages, K1 serum agar plates and Latex agglutination and ELISA using an IgG2a anti K1 monoclonal antibody. In total, 33 sepsis isolates (about 18%) were identified as K1 positive, with three of these strains proving negative in all tests except those exploiting the monoclonal antibody. That these three strains elaborate the K1 antigen was confirmed by Southern blot experiments using cloned K1 antigen production genes as probes. The failure of the three strains in all the tests except those that use monoclonal antibody could be explained by apparent disruption of K1 gene sequences that encode functions essential for the export of capsular material to the cell surface. The superiority of tests based on monoclonal antibodies above the conventional methods for detection of K1 antigen is evident. PMID- 3333803 TI - A unique amino acid sequence of the B subunit of a heat-labile enterotoxin isolated from a human enterotoxigenic Escherichia coli. AB - The purified B subunit of heat-labile enterotoxin produced from a human strain, 240-3, of enterotoxigenic Escherichia coli (LTh(240-3] was carboxymethylated, succinylated, digested with chymotrypsin and subjected to high performance liquid chromatography (HPLC), and the amino acid compositions of the peptide peaks from the column were analyzed and compared with the data reported by Yamamoto and Yokota (J. Bacteriol. 155, 728.1983), who deduced the amino acid sequence of LTh(H10407) from the DNA sequence of a human strain H10407. Only one fraction differed in amino acid composition from that reported by them. This fraction was found to consist of peptides with the sequences Arg-Asn-Thr-Gln-Ile-Tyr and Arg Ile-Ala-Tyr. Yamamoto and Yokota reported the sequence of the latter peptide as Arg-Ile-Thr*-Tyr, which corresponds to the peptide from 73rd to 76th from amino (N-) terminus. Thus amino acid residue 75 from the N-terminus of LTh-B(240-3) is alanine, not threonine. The B subunit of cholera toxin also has alanine at position 75. LTh(240-3) appeared similar to LTh(H10407) in an Ouchterlony test, vascular permeability test and GMI ganglioside ELISA. These data show that substitution of threonine for alanine at position 75 from the N-terminus does not affect the immunological and biological characteristics of LTh. PMID- 3333804 TI - Measurement in human sera of antibodies to lipopolysaccharide of Escherichia coli J5. PMID- 3333805 TI - Antibody response to Escherichia coli J5 lipopolysaccharide in patients with bacteremia. PMID- 3333806 TI - Binding of fibronectin, fibrinogen and type II collagen to streptococci isolated from bovine mastitis. AB - Binding of 125I-labelled fibronectin, fibrinogen and type II collagen to group B (S. agalactiae), group C (S. dysgalactiae and S zooepidemicus), group E (S. uberis) and nontypable streptococci isolated from bovine mastitis was studied. S. agalactiae and S. uberis were found to bind low levels of all three proteins, while S. zooepidemicus bound high levels. Binding of the proteins to S. dysgalactiae varied, i.e. fibronectin was high, fibrinogen moderate and collagen low. Nontypable strains showed moderate or low binding of all proteins. Both hydrophobic and hydrophilic strains were found to bind fibronectin. For S. dysgalactiae the specific fibronectin binding ranged from 70% to 10% and for S. zooepidemicus it was more than 80% and this binding was sensitive to papain treatment. The binding of 29K-fibronectin fragment to one S. dysgalactiae strain showed an affinity of KD = 2.6 x 10(-8) M and the number of binding sites per colony forming unit (CFU) was calculated at 11,000. PMID- 3333807 TI - Studies on Trypanosoma rangeli Tejera, 1920. IX. Course of infection in different stages of Rhodnius prolixus. AB - Frequent individual observations od different stages of Rhodnius prolixus exposed to Trypanosoma rangeli, revealed a higher susceptibility to infection in the bugs exposed during the two first instars. The mortality rate in infected bugs was significantly higher than in controls, indicating that the parasite was responsible for the majority of deaths. An analysis of the mortality distribution, per instar, is presented. Statistical analysis of deaths among the different infected instars, showed that T. rangeli produces its pathological effect in any stage of R. prolixus independently of its susceptibility to the parasite. The survival to adult decreased in all the infected instar bugs. A significant longer time to reach the adult stage was observed in the infected bugs when compared with controls, excepting for specimens exposed in the third instar. The epidemiological significance of the present results is discussed. PMID- 3333808 TI - Behavior of triatomines (Hemiptera: Reduviidae) vectors of Chagas' disease. III. Influence of the number of matings on the fecundity and fertility of Panstrongylus megistus (Burm., 1835) in the laboratory. AB - A study of the effect of mating in the fecundity and fertility of females of P. megistus fed on pigeon blood every 14 days, was carried out in the laboratory. Two groups were constituted: I - females which mated only once; II - females which stayed always with the males. Only 56.7% of group I females laid fertile eggs, while as much as 90% of group II females laid fertile eggs. The duration of the fertile oviposition was greater in the females which stayed always with the males. Some females of this group were able to mate up to seven times throughout their life-span. This fact render useless sterile males in the control of these insects. PMID- 3333809 TI - [Serotype characterization of Escherichia coli potentially producing enterotoxins in foods]. AB - The incidence of serotypes of Escherichia coli usually described as enterotoxins producer was investigated in 137 samples of food from different origins (animal and vegetal). The serological analysis of the somatic "O", capsular "K" and flagellar "H" antigens in 265 isolates of Escherichia coli resulted in the characterization of 34 strains, distributed in 12 serotypes. These organisms were obtained from 24 samples of food of animal origin. A possible association with epidemiological markers for other test, were analyzed. The fermentation pattern of the 34 strains with melibiose, raffinose, sucrose, salicin, and sorbitol allowed classification into 11 biotypes. However the marked heterogenicity of the biotypes distributed among the serotypes did not allow correlation between the serofermentative types and the origin of the food. The other tests based on hemolysis and hemagglutinating ability did not aid in the differentiation of the phenotypes. PMID- 3333810 TI - [Fecal coliforms in sewage waters. I. Resistance to antibiotics, heavy metals and colicinogeny]. AB - Qualitative bacteriological analysis was carried out in two sewage treatment plants in the city of Rio de Janeiro during the period 1984-1985. Specific points of the plants were selected for the collection of affluent and effluent samples. The study involved the isolation and the identification of 540 cultures of Escherichia coli that were analyzed for their resistance to eight antibiotics (sulfadiazine, streptomycin, tetracycline, chloramphenicol, kanamycin, ampicillin, nalidixic acid and gentamycin), and three heavy metals (copper sulphate, mercuric chloride and zinc sulphate) as well as colicinogeny. About 95% of the isolated cultures from the effluents had genetic markers while the samples originated from the affluents showed 70%. PMID- 3333811 TI - The transmission of suprapylarian leishmania by the bite of experimentally infected sand flies (Diptera: Psychodidae). AB - Lutzomyia furcata transmitted Leishmania chagasi to a hamster 10 days after being experimentally fed on an infected spleen. An individual female Psychodopygus carrerai carrerai that had fed on a hamster lesion caused by Leishmania mexicana amazonensis transmitted this parasite 6 days later to another hamster. Transmission electron microscopy of this fly's head revealed a small number of degenerate promastigotes in the foregut, but only a few were attached. PMID- 3333813 TI - Obstructive sleep apnea. Diagnosis, treatment and pathophysiology. PMID- 3333812 TI - Leishmania infantum, the aetiological agent of American visceral leishmaniasis (AVL)? PMID- 3333814 TI - Obstetrical sonography. Some significant implications in antepartum management. PMID- 3333815 TI - Screening and detection of colon cancer. PMID- 3333816 TI - A decade of genetic counseling. PMID- 3333818 TI - New approaches to streptococcal pharyngitis. PMID- 3333817 TI - Early experience with cyclosporine in renal transplantation. PMID- 3333819 TI - [Neuromuscular disturbances in functional pathology of the stomatognathic system]. PMID- 3333821 TI - [Functional changes in the stomatognathic system induced by orthognathic surgery]. PMID- 3333820 TI - [Leukoplakia of the oral mucosa. Current review]. PMID- 3333822 TI - [Pulp calcifications]. PMID- 3333823 TI - Provisional restorations. Part 1. PMID- 3333824 TI - Sampling of subgingival plaque: a comparison of two methods using darkfield microscopy. PMID- 3333825 TI - Bacteroides forsythus in adult gingivitis and periodontitis. PMID- 3333826 TI - Media for cultivation of Eikenella corrodens and formate-and fumarate-requiring species of oral bacteria. PMID- 3333827 TI - The removal of phosphoric acid and calcium phosphate precipitates: an analysis of rinse time. PMID- 3333828 TI - Dental defects in incontinentia pigmenti: case report. PMID- 3333830 TI - Prevalence of craniomandibular dysfunction in children and adolescents: a review. PMID- 3333829 TI - Localized scleroderma in childhood: review of the literature and case report. PMID- 3333831 TI - Tuberculous osteomyelitis in the mandible of a child. PMID- 3333832 TI - Special inlay double issue--Part one. PMID- 3333833 TI - Special inlay double issue--Part two. PMID- 3333834 TI - Biology of melanoma invasion and metastasis. PMID- 3333835 TI - Temporal synthesis and presentation of antigens by cultured B16 melanoma cells. AB - Previous studies have demonstrated the presence of two distinct antigens, B700 and B50, which are unique to murine melanoma. One of these, B700 has been studied in detail, and is present on 5 different murine melanomas; it can function as a transplantation antigen in at least 3 of them (B16, JB/RH and K1735). The synthesis and presentation of these antigens has been studied as a function of cell culture conditions. Direct immunofluorescence studies of cells in serial culture indicate that the expression of B700 and B50 antigens at the cell surface and in the cytoplasm increases as a function of time in culture, over 1-5 days. By day 5, when the cells are confluent, all cells show some degree of antibody binding. Parallel 35S-methionine pulse chase labeling experiments show that incorporation into Triton soluble proteins, and Triton insoluble SDS soluble proteins, increases to a peak at 3.5 days after subculturing, then decreases as the cells reach confluence. Incorporation into proteins shed into the culture supernatant continued throughout the time course of cell growth to confluence. However, as the cells become confluent, total protein synthesis shifts towards greater production of the antigens (both cellular and shed). The sum of the results suggest that tumor growth may succeed in vivo by the wholesale production of "decoy" antigens. PMID- 3333836 TI - Permeabilized cell models for the study of granule transport in pigment cells. PMID- 3333839 TI - [Our experience with direct fixation of locks onto the tooth dentin]. PMID- 3333838 TI - [Evaluation of the material Silar in scanning electron microscope]. PMID- 3333837 TI - [Periodontology in Soviet stomatology]. PMID- 3333840 TI - Expression of the amino terminal part of synthetic human growth hormone gene and somatomedin-like activity of expressed protein. AB - We have constructed three different plasmids containing parts of the human growth hormone gene using chemically synthesized oligomers and cloned them for the purpose of expressing them in Escherichia coli. AB, B and BC gene segments corresponding to ABhGH (residue 1-138), BhGH (residue 44-138) and BChGH (residue 44-192) were placed under the control of a tryptophan promoter in the expression vector. Upon induction with 3-indolylacrylic acid, ABhGH accumulated in cells but the BhGH and BChGH segments were not detected appreciably. Northern blotting analysis showed that the amount of mRNA transcribed from the AB gene segment was about ten-fold higher than that from the B or BC gene segment. ABhGH was found to have insulin-like growth factor I (IGF-I) activity, which could be explained by the hydrophilicity curves of these proteins. PMID- 3333841 TI - What is protein engineering? PMID- 3333842 TI - Protein engineering of alcohol dehydrogenase--1. Effects of two amino acid changes in the active site of yeast ADH-1. AB - One of the promises held out by protein engineering is the ability to alter predictably the properties of an enzyme to enable it to find new substrates or catalyse existing substrates more efficiently, such manipulations being of interest both enzymologically and, potentially, industrially. It has been postulated that in yeast alcohol dehydrogenase (YADH-1) certain amino acids such as Trp 93 and Thr 48 constrict the active site due to their bulky side chains and thus impede catalysis of molecules larger than ethanol. To study effects of enlarging the active site we have made two changes into YADH-1, replacing Trp 93 with Phe and Thr 48 with Ser. Kinetic experiments showed that this enzyme had marked increases in reaction velocity for the n-alcohols propanol, butanol, pentanol, hexanol, heptanol, octanol and cinnamyl alcohol compared to the parent, agreeing with the prediction that expanding the active site should facilitate the oxidation of larger alcohols. The substrate affinities were slightly reduced in the altered enzyme, possibly due to its having reduced hydrophobicity at Phe 93. PMID- 3333843 TI - Protein engineering. PMID- 3333844 TI - Protein engineering by chemical means? PMID- 3333845 TI - Site-directed mutants of the cAMP receptor protein--DNA binding of five mutant proteins. AB - Oligonucleotide-directed mutagenesis was employed to generate mutants of the cAMP receptor protein (CRP) of Escherichia coli. The mutant proteins were purified to homogeneity and tested for stability and DNA binding. It is shown that mutations at the position of Arg180 abolish specific DNA binding, whereas those at the position Arg185 have very little effect. Both positions have previously been implicated as crucial for the specific interaction between CRP and DNA. The Ser128----Ala mutant shows a slight reduction in DNA binding affinity relative to wild-type. All mutants investigated show similar stability profiles to wild-type CRP with respect to thermolysin proteolysis as a function of temperature. PMID- 3333846 TI - Soluble, prolonged-acting insulin derivatives. I. Degree of protraction and crystallizability of insulins substituted in the termini of the B-chain. AB - Hydrophilic insulins, more positively charged than human insulin at neutral pH, have been prepared by substitution with basic amino acids at the termini of the B chain and by blocking the C-terminal carboxyl group of the B-chain. The isoelectric pH of the insulin is thereby moved from 5.4 towards physiological levels. Slightly acid solutions of derivatives, in which charge has been added in the C-terminus of the B-chain, have a prolonged action in vivo, in particular if the carboxyl group is blocked. It is found that the prolonged-acting hydrophilic insulins crystallize instantly when the pH is adjusted to 7. The prolonged action is ascribed to this readiness to crystallization combined with a low solubility, which may be further decreased by increased concentration of zinc ions. Hydrophobic insulins have a prolonged action independent of the site of substitution even if the derivative is soluble at physiological pH. Some derivatives were prepared from porcine insulin by tryptic transpeptidation. N terminal B-chain substituted insulins were prepared by alkylation of a biosynthetic single-chain insulin precursor, followed by tryptic transpeptidation rendering the double chain insulin derivative. The observed blood glucose lowering in the rabbits implies that neither N- nor C-terminal B-chain substitution results in substantial deterioration of biological potency. An index for the degree of protraction based on the blood glucose data is used to compare the insulins. PMID- 3333848 TI - Long-term management of multiple osseous defects with sclera allografts. PMID- 3333847 TI - Soluble, prolonged-acting insulin derivatives. II. Degree of protraction and crystallizability of insulins substituted in positions A17, B8, B13, B27 and B30. AB - It has previously been found that insulins, to which positive charge has been added by substitutions in position B30, thus raising the isoelectric point towards pH 7, had a prolonged action when injected as slightly acidic solutions because such derivatives crystallize very readily upon neutralization. Positive charge has now been added by substituting the B13 and A17 glutamic acid residues with glutamines and B27 threonine with lysine or arginine. These substitutions were introduced by site-specific mutagenesis in a gene coding for a single-chain insulin precursor. By tryptic transpeptidation the single-chain precursors were transformed to the double-chain insulin structure, concomitantly with incorporation of residue B30. Thus insulins combining B13 glutamine, A17 glutamine and B27 lysine or arginine with B30 threonine, threonine amide or lysine amide were synthesized. The time course of blood glucose lowering effect and the absorption were studied after subcutaneous injection in rabbits and pigs. The prolonged action of B30-substituted insulins was markedly enhanced by B27 lysine or arginine substitutions and by B13 glutamine. The B27 residue is located on the surface of the hexamer, so a basic residue in this position presumably promotes the packing of hexamers at neutral pH. The B13 residues cluster in the centre of the hexamer. When the electrostatic repulsive forces from six glutamic acid residues are abolished by substitution with glutamine, a stabilization of the hexamer can be envisaged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333849 TI - The use of collagen materials in bone grafted defects to enhance guided tissue regeneration. PMID- 3333850 TI - Osseous repair with and without the use of bone grafts. PMID- 3333851 TI - Management of fractured tooth based upon biologic principles. PMID- 3333852 TI - Bonded composite resin crown restoration without enamel reduction. PMID- 3333854 TI - Relationship between overhanging amalgam restorations and periodontal disease. PMID- 3333853 TI - The flow of zinc phosphate cement under a full-coverage restoration and its effect on marginal adaptation according to the location of cement application. PMID- 3333856 TI - The P-S (Pin-Slot) attachment, as utilized for the Thompson dowel in removable partial dentures. PMID- 3333855 TI - Experimental use of a bonding agent to reduce marginal microleakage in amalgam restorations. PMID- 3333857 TI - The plastic postpalatal denture seal. PMID- 3333858 TI - Some treatment alternatives for dealing with the enlarged maxillary tuberosity. PMID- 3333859 TI - Bond strength of mechanically condensed repaired high-copper amalgam. PMID- 3333860 TI - Penetration of acid gel etchants into cavity walls: an SEM evaluation. PMID- 3333861 TI - Cement retention of porcelain crowns. PMID- 3333862 TI - A regulatory approach to the formulation of assessment criteria for posterior composite resins. PMID- 3333863 TI - Temporary tooth separation with special reference to the diagnosis and preventive management of equivocal approximal carious lesions. PMID- 3333864 TI - [Current methods of laboratory diagnosis of syphilis of the central nervous system]. PMID- 3333865 TI - [Treatment of systemic scleroderma with fucidin in relation to clinical evaluation and analysis of free amino acids in the serum]. PMID- 3333866 TI - [Dysplastic pigmented nevi as a high risk group for the development of malignant melanoma]. PMID- 3333868 TI - [Corrosion of silver cones: current status]. PMID- 3333867 TI - [Occurrence of autoantibodies and the clinical course of mixed connective tissue disease, systemic scleroderma, dermatomyositis, polymyositis and Sjogren's syndrome]. PMID- 3333869 TI - The effect of chlorinated disinfecting solutions on alginate impressions. PMID- 3333870 TI - Teaching aids in removable partial denture design. PMID- 3333871 TI - [In vivo resistance of Plasmodium falciparum to 4-aminoquinolines and to a sulfadoxine-pyrimethamine combination. II--The Emperatriz study, Maranhao, 1983 1984]. PMID- 3333872 TI - Studies on anti-component 5 antibodies in animals infected with Trypanosoma cruzi. PMID- 3333874 TI - [Epidemiologic information on malaria in the state of Sao Paulo, Brazil]. PMID- 3333873 TI - [Comparative study of the development cycle of Rhodnius neglectus fed on pigeons or mice]. PMID- 3333877 TI - [When hepatic fibrosis becomes a disease...]. PMID- 3333875 TI - Frequency of human leukocyte antigen (HLA) in patients with malaria and in the general population of Humaita County, Amazonas State, Brazil. PMID- 3333876 TI - [A case of indigenous polycystic hydatidosis in Minas Gerais, Brazil]. PMID- 3333878 TI - Effects of levamisole on experimental infections by Plasmodium berghei in mice. PMID- 3333879 TI - [Human lagochilascariasis in Venezuela: description of a fatal case]. PMID- 3333880 TI - [Uncommon aspects of infantile paracoccidioidomycosis]. PMID- 3333881 TI - Aspects of anticoagulant action: a review of the pharmacology, metabolism and toxicology of warfarin and congeners. AB - Warfarin is the most widely used anticoagulant in the treatment of thromboembolism in man. It has also been used extensively as a rodenticidal agent. Insofar as its clinical use is concerned, it is now clear that many of the drug interactions observed in patients are mediated via metabolic or pharmacokinetic factors. An understanding of the disposition of warfarin is therefore essential if one is to predict the likely response in patients undergoing anticoagulant therapy with this compound. Warfarin-resistance has been reported in both man and rodents. Understanding resistance in both man and rodents is important for effective anticoagulant therapy, and in control of resistant strains of rodents. Warfarin resistance in rat strains does not appear to have a metabolic or pharmacokinetic basis; in this species, resistance is thought to be due to differences in permeability to, or affinity for a receptor. Apart from its clinical and rodenticidal uses, warfarin is an excellent substrate for probing the heterogeneity of cytochrome P.450, since its metabolic oxidation is mediated by this mixed function oxidase. This review draws together much of the current published literature on the pharmacology, metabolism and toxicology of warfarin and related congeners. PMID- 3333882 TI - The metabolism and biopharmaceutics of spironolactone in man. AB - Spironolactone, a competitive aldosterone antagonist, has been used for almost 30 years in those disorders associated with primary or secondary hyperaldosteronism. This review is confined to its metabolism and biopharmaceutics in man. Spironolactone undergoes extensive metabolism with no unchanged drug appearing in the urine. Its metabolites can be divided into two main categories: those in which the sulfur of the parent molecule is removed and those in which the sulfur is retained. The dethioacetylated metabolite canrenone, belonging to the former category, was long considered to be the major active metabolite of spironolactone. For this reason pharmacokinetic studies have focussed on its kinetic behaviour. However, pharmacodynamic studies indicated that canrenone could only partly explain spironolactone's action. Furthermore, with the advent of modern high-performance liquid chromatographic techniques to measure canrenone concentrations, it was shown that previously employed assay techniques were unspecific and consequently considerably overestimated true canrenone levels. Recently, it was demonstrated that after a single oral dose of spironolactone, 7 alpha-thiomethylspirolactone is the main metabolite and that unchanged spironolactone reaches maximum serum concentrations which are in the same order of magnitude as canrenone. Both spironolactone and 7 alpha-thiomethylspirolactone are known to possess anti-mineralocorticoid activity, and they may be mainly responsible for the activity of spironolactone. It also appears likely that endocrine side effects of spironolactone, such as gynaecomastia, are mediated by these sulfur-containing compounds. The oral absorption of spironolactone is improved by using micronized drug or inclusion complexes of spironolactone with cyclodextrins. Concomitant food intake has also been shown to enhance the bioavailability, by increasing the absorption and decreasing the first-pass effect of spironolactone. PMID- 3333883 TI - [Fluoride: are these reasons for controversy?]. PMID- 3333884 TI - [Adhesives in dentistry. Considerations in the clinical use of dentin adhesives and enamel/dentin adhesives]. PMID- 3333885 TI - [Copper-aluminum alloys. Casting contraction of various copper-aluminum system alloys]. PMID- 3333886 TI - [Alternative casting alloys]. PMID- 3333887 TI - Canine lymphoma: clinical considerations. PMID- 3333888 TI - Current concepts in cancer therapy: biologic therapy and chemotherapy. PMID- 3333889 TI - Acute tumor lysis syndrome. PMID- 3333890 TI - [Phase I study of a tolmetin-paracetamol (AU-8001) ester]. AB - A cross-over study of a tolmetin-paracetamol ester was performed on 6 healthy females. The low biodisponibility obtained might preclude its therapeutic use. PMID- 3333891 TI - [Non-tuberculous infections of the spine]. AB - Non tuberculous spondylodiscitis of the rachis is an uncommon entity that affects boys and male adults with greater frequency. The zone with higher incidence of affection is the lumbar region. Usually the causal germ travels through the hematogenous via from an extrarachidial infectious area. Clinical manifestations begin with an acute segmentary rachialgia and paravertebral muscular contracture while presenting fever. In special cases of little boys or when having radiated pain, the presenting form could be confusing. There is always a vertebral rigidity when performing the physical exam and an increase of the globular sedimentation rate. A septic leukocytal formula is not always present. Between the onset of symptoms and the appearance of radiologic alterations (decrease in the height of the disc, erosion and vertebral destruction, reactive bone neo formation) there is a variable two to eight weeks latency period. Scintigraphy with Tc99 and Ga67 and CAT scan are very important when facing definite diagnosis. To be able to reach a bacteriological diagnosis, we employ puncture aspiration of the disc. The isolated germ in most cases is staphylococcus aureus. The most complex differential diagnosis is with tuberculous spondylodiscitis. The evolution is favorable if the treatment is initiated early and if it is adequate (antibiotic therapy and immobilization). If this is not done, recurrences and chronicity of the infection can occur, as well as orthopaedic (Kyphosis) and neurological complications. PMID- 3333892 TI - [Intra-arterial chemotherapy, using the hepatic artery, in metastases of colorectal carcinoma]. AB - Hepatic metastasis is the major cause of death in advanced cancer of the colon and rectum. Various modes of therapy have been attempted with only partial success. Infusion of cytotoxic agents into the hepatic artery has allowed a higher concentration of drug into the tumor capillary bed than is achievable with intravenous administration. We review the data on therapeutic outcome, administration techniques and toxicity of hepatic arterial chemotherapy for colorectal cancer metastatic to the liver. PMID- 3333893 TI - Laboratory evaluation of antiarthritic drugs as potential chondroprotective agents. PMID- 3333895 TI - Reference list of biomedical and clinical publications. Uppsala 1985. PMID- 3333894 TI - Long-term studies of antiosteoarthritic drugs: an assessment. PMID- 3333897 TI - [The 70th anniversary of Soviet blood transfusion]. AB - The article describes the achievements of transfusiology in the USSR for the period from 1917 till 1987. The leading role of Soviet scientists in the development of all main problems of the present-day transfusiological science and practice is stressed. PMID- 3333896 TI - [The 150th anniversary of the publication of N.I. Pirogov's work "Surgical anatomy of arterial trunks and fascia"]. PMID- 3333898 TI - [Surgical tactics in diverticulosis of the sigmoid]. AB - The article presents an experience with the surgical treatment of 27 patients with diverticulosis of the sigmoid colon. It was established that the indications and operation volume should be individualized in correlation with the complication of diverticulosis. In weak patients with critical concomitant diseases good results were obtained after operation of exclusion of the left half of the colon. A modification of the Hartman operation is proposed which reduces the danger of incompetence of the rectum stump sutures and makes the time of treatment shorter. PMID- 3333900 TI - [Development of surgery of the stomach during the 70-year period of Soviet rule]. PMID- 3333899 TI - [Variants of microsurgical autologous transplantation of composite skin flaps from the external surface of the hip]. AB - Topographic anatomical investigations have established the possibility to make a new complex skin flap on the lateral surface of the femur on the branches of the second perforating artery and vein. The authors propose methods of making a transplant in this field on two vascular pedicles with anastomoses in one of them -a larger one and two separate flaps: a skin-fat and a muscular flaps on a single feeding pedicle. The experimental findings were confirmed by successful clinical observations. PMID- 3333901 TI - [Reparative processes and the possibilities of their stimulation in the over cooled body]. PMID- 3333902 TI - [Bilateral tumors of the kidney. 2 case reports and a review of the literature]. PMID- 3333903 TI - [Proximal gastric vagotomy with single-layer sutures--the method of choice in perforated duodenal ulcers (15 years' experience)]. PMID- 3333904 TI - [Single-layer sutures in the surgical treatment of the large intestine]. PMID- 3333905 TI - [A classification system of precision attachments]. PMID- 3333906 TI - [Synopsis of the history of dentistry in Antioquia]. PMID- 3333907 TI - [Hygienic period and reevaluation in the integrated treatment of the adult]. PMID- 3333908 TI - [Controversies in occlusion and their implications for orthodontics]. PMID- 3333909 TI - [The Venezuelan state, popular participation and health]. PMID- 3333911 TI - Computers in nursing education. PMID- 3333910 TI - [Microfiltration as a clinical problem]. PMID- 3333912 TI - [The evaluation of different experimentally induced thermal changes conducted to the pulp tissue after chemical and mechanical cementum curettage]. PMID- 3333913 TI - [Measurement of bite forces in Maryland bridges using strain gauge technique]. PMID- 3333914 TI - [Median mandibular cyst]. PMID- 3333915 TI - [Restoration with a fixed-removable partial denture in patients who have extensive supportive tissue loss]. PMID- 3333916 TI - [Prosthetic management in hydrotic and anhydrotic ectodermal dysplasia: report of 6 cases]. PMID- 3333917 TI - [The immune system and AIDS]. PMID- 3333918 TI - [Comparison of invasive and non-invasive diagnostic methods in temporomandibular joint intra-capsular dysfunction]. PMID- 3333919 TI - Presentation of Honorary Fellowship to Professor Sir John Butterfield. PMID- 3333920 TI - Presentation of the Academy plaque to Norbert J. Roberts, M.D. PMID- 3333921 TI - Presentation of the Academy Medal to Thomas C. Chalmers, M.D. PMID- 3333922 TI - Radiologic diagnosis of pain in the athlete. AB - This article provides an overview of the various radiographic procedures available today. The correct indications for the use of each of these is emphasized and illustrated. PMID- 3333923 TI - The role of nuclear medicine bone scans in evaluating pain in athletic injuries. AB - The utilization of nuclear medicine bone scanning examinations early in the diagnostic process allows physicians to render prompt and correct treatment in urgent or difficult athletic cases. Bone scanning should be performed for athletic injuries whenever (1) x-rays are normal but bone or joint pain persists; (2) x-rays are positive but it cannot be determined if the findings are acute or chronic; (3) soft-tissue injuries present and x-rays are not useful; and (4) bone pain or joint impairment present without a history of trauma. PMID- 3333924 TI - Headache in the athlete and radiographic evaluation. AB - A deliberate attempt is made to stress the nonspecificity of headache and the complexity of its work-up. The choice of radiographic studies for its evaluation should be governed by the strongly considered etiology. This article deals with the most likely causes of headaches in an athlete. The merits and limitations of currently available radiographic modalities to detect headache-producing diseases are broadly discussed. PMID- 3333925 TI - Roentgen examination of cervical spine injuries in the athlete. AB - The roentgen evaluation of the cervical spine must be performed immediately following the possibility of injury and in such a manner as not to compromise the neurologic status of the patient. Subtle roentgen findings indicating ligamentous injuries must be recognized so that they can be treated prior to developing cervical spine instability. Occult fractures, which may be difficult to diagnose on plain films and require multiple radiographic modalities, must be diagnosed so as to prevent prolonged intractable neck pain. Most importantly, recognizing the mechanism of injury and prevention of cervical spine injuries are critical to prevent catastrophic cervical spine injuries secondary to athletic participation. PMID- 3333926 TI - Lumbar and thoracic spine pain in the athlete: radiographic evaluation. AB - A comprehensive but basic and updated systematic radiographic approach to various pain-producing thoracolumbar diseases is presented. The advantages and limitations of available diagnostic modalities are discussed in relation to the clinically considered etiologies. PMID- 3333927 TI - The radiographic evaluation of shoulder and elbow pain in the athlete. AB - This article presents the important anatomic features of the shoulder joint and the abnormalities to which the athlete is most susceptible leading to pain and disability. It also reviews the pertinent elbow anatomy and discusses the radiographic techniques currently employed in diagnosing elbow problems in the athlete, including tomography, arthrography, and computed tomography. PMID- 3333928 TI - Radiology of wrist and hand injuries in athletes. AB - Traumatic injuries are a major cause of hand and wrist pain in athletes. Wrist injuries include fractures, dislocations, and instability patterns. Hand injuries include tendon injuries, ligamentous injuries, and fractures. In this article we have presented the radiographic appearance of the more common of these injuries. PMID- 3333929 TI - Roentgen examination of groin and hip pain in the athlete. AB - Stress fractures and reactions of the pubic ramus, pubic symphsitis, gracilis syndrome, pelvic avulsion injuries, femoral stress fractures, degenerative osteoarthritis, discogenic pain, and spondylolysis are among the multiple conditions causing groin pain in the athlete. These conditions occasionally have uncertain etiologies and are contributed to by poor training techniques and ill repaired running shoes, combined with minor congenital anomalies that may have been silent prior to the demands of athletic competition. Roentgen documentation of the specific injury enables early appropriate treatment and minimal "down time". PMID- 3333930 TI - The radiologic evaluation of chest pain in the athlete. AB - Chest pain in the athlete may arise from any one of a number of diverse etiologies. Many of these entities are discussed using an organ system approach. The pathophysiology and clinical characteristics of these processes are described and imaging studies that may aid in establishing their diagnosis are discussed. PMID- 3333931 TI - Pain in the athlete's knee. AB - When the athlete develops knee pain, conventional radiographs are often helpful to establish the correct diagnosis. Knee arthrography may provide additional information when conventional radiography shows no specific abnormality. A number of causes of knee pain in the athlete are illustrated. PMID- 3333932 TI - Abdominal pain in athletes. AB - Abdominal pain in an athlete may be due to an intra-abdominal injury or abdominal disease unrelated to athletics; both are uncommon. Because such processes may be life-threatening, awareness of their typical patterns is imperative for all involved in sports medicine. Evaluation of an athlete with abdominal pain is thus directed at deciding if the athlete has significant abdominal disease, and then using appropriate diagnostic methods to determine the specific process. PMID- 3333933 TI - Absorption kinetics of regular and isophane (NPH) insulin in the normal dog. AB - Absorption kinetics of regular and isophane (NPH) insulins were evaluated in seven normal fasted dogs by measuring serial serum concentrations of insulin and glucose following the subcutaneous administration of regular and NPH insulins. These results were compared to serum insulin values determined after injecting similar doses of regular insulin intravenously. Regular insulin was better absorbed than NPH insulin (mean bioavailability index 64.6% vs. 41.1%, P less than .01) resulting in a significantly greater maximal increase in mean circulating insulin concentrations above baseline values (362.2 microU/ml vs. 147.8 microU/ml, P less than .05). The time interval between insulin injection and return of serum insulin values to basal concentrations was also significantly shorter for regular than for NPH insulin (4.9 hr vs. 8.6 hr, P less than .05). However, there were no significant differences between regular and NPH insulins in time to reach peak serum insulin concentrations, maximal reduction in serum glucose concentrations, or time of lowest circulating glucose levels. The results of this study support previously accepted values for time-action characteristics of regular insulin, but suggest that NPH insulin may have an earlier peak and shorter duration of action than has previously been proposed in the dog. PMID- 3333935 TI - Embryo-derived platelet activating factor: a preimplantation embryo mediator of maternal recognition of pregnancy. PMID- 3333934 TI - Effects of zeranol on protein turnover in L6 myotubes. AB - Protein synthesis and degradation were measured in cultures of L6 myotubes to determine the direct anabolic activity of zeranol on muscle. Zeranol, dexamethasone, insulin and zeranol-dexamethasone combination, at various concentrations from 10(-8) to 10(-6) M, were added to cultures at either 18 hr prior to or at the beginning of a 6 hr synthesis or degradation measuring period. Protein synthesis was measured by determining the incorporation of radioactivity into trichloraoacetic acid precipitable cell protein following incubation with [3H] leucine. Protein synthesis was expressed as cpm incorporated in 6 hr per mg protein. Protein degradation was measured by a pulse-chase procedure using [3H] leucine. Protein degradation was expressed as the percent labeled protein degraded in 6 hr. Results from the study indicate that zeranol did not stimulate protein synthesis or inhibit proteolysis (P greater than .01). Stimulation of proteolysis observed with 10(-8) M dexamethasone was 13% and 18% (P less than .01) at the 6 hr and 24 hr incubation period, respectively. Dexamethasone stimulated protein degradation was not altered appreciably by zeranol. In contrast, 10(-6) M insulin significantly (P less than .01) stimulated protein synthesis (16%) and inhibited protein degradation (15%). These results suggest that the anabolic action of zeranol does not occur by directly regulating muscle protein synthesis or degradation, or by altering the glucocorticoid-induced catabolic response in muscle. PMID- 3333936 TI - [Luxations, reimplantations, transplantations]. PMID- 3333937 TI - [A method for resolution of anterior migration problems]. PMID- 3333938 TI - Imaging characteristics in rotational panoramic radiography. PMID- 3333939 TI - Purification of M. leprae with special reference to the effects of purified M. leprae vaccines on host macrophage cell functions. PMID- 3333940 TI - [Infection of Mycobacterium leprae and Mycobacterium lepraemurium into a cloned macrophage like cell line]. PMID- 3333941 TI - [Collection method of Mycobacterium leprae from infected armadillo liver--a comparison with Draper's method]. PMID- 3333942 TI - [Inactivation methods of Mycobacterium leprae as a leprosy vaccine]. PMID- 3333943 TI - The effects of Bendaline on cataracts. PMID- 3333945 TI - Behavior of triatomines (Hemiptera:Reduviidae) vectors of Chagas' disease. IV. Fecundity, fertility and longevity of Panstrongylus megistus (Burm., 1835) pairs and virgin females starved under laboratory conditions. AB - A laboratory study was conducted on the fecundity, fertility and life span of Panstrongylus megistus pairs and on the fecundity and life span of P. megistus virgin females submitted to starvation after the last moulting. Of the mated females, 22.2% laid eggs, 4.4% of which were fertile. Females resisted starvation more than males. Of the starved virgin females, only 10% laid eggs, with a low egg-laying rate (0.47) per female. Resistance to starvation was lower in virgin than in mated females. PMID- 3333946 TI - [Vital statistics of Rhodnius neivai Lent, 1953 (Hemiptera: Reduviidae) under experimental conditions]. AB - A statistical evaluation of the population dynamics of R. neivai is based on six cohorts experiments conducted under controlled laboratory conditions. Two blood sources were offered to animals: rabbit and hen. Egg hatching, nymphal development time and mortality, adult longevity and age-specific mortality, female age-specific fecundity and fertility were determined. In addition, some population parameters were evaluated, such as: life expectancy, intrinsic rate of natural increase, net reproduction rate, finite rate of increase, reproductive value and stable age distribution. Life cycle was longer in the animals fed on rabbit, nymphal survival was slightly higher in the individuals fed on hen. Age of first reproduction was lower in the insects fed on hen, but reproductive output and total number of reproductive weeks were greater in the cohorts fed on rabbit. Intrinsic and finite rate of increase were greater in the animals fed on hen. Generation time was slightly greater in the cohorts fed on rabbit. Net reproduction rate was similar on both blood sources, although it was slightly bigger in the individuals fed on rabbit. Reproductive value in the insects fed on rabbit was twice as much as the registered in the animals fed on hen. PMID- 3333944 TI - Epidemiological aspects of toxoplasmosis in schoolchildren residing in localities with urban or rural characteristics within the city of Rio de Janeiro, Brazil. AB - Immunofluorescence tests (IF) for toxoplasmosis were performed on a total of 608 schoolchildren in elementary and junior high grades. 166 being in the Bonsucesso district (an urban region of Rio de Janeiro) and 442 children from locations within the lowlands of Jacarepagua (with rural characteristics). All the IF-IgM were nonreactive, whilst 416 schoolchildren (68.4%) were IF-IgG serum-reactive (greater than or equal to 1:16). The percentages of serum-reactives in Jacarepagua were significantly higher than in Bonsucesso, both as regards the total number of schoolchildren (p less than 0.001), as also when subdivided according to the age-grades from six to eight years (p less than 0.001) or from twelve to fourteen (p less than 0.05). Both in Jacarepagua and in Bonsucesso, the prevalence of reactions in the 12 to 14 year age-grade was significantly greater than in the 6 to 8 year age-grade (p less than 0.001 in both cases). Expressively larger prevalences of serum reactions were found in Jacarepagua among schoolchildren who preferred eating raw or undercooked meat, as well as among those having cats as pets; this occurred equally in the 6 to 8 year and in the 12 to 14 year age-grades. In Bonsucesso, the only significant difference was in the 6 to 8 year age-grades that had cats as pets. Thus, it has been verified that the risk of infection is greater and more precocious in localities with rural characteristics than in urban regions. PMID- 3333947 TI - [Esthetics in removable partial dentures]. PMID- 3333948 TI - [Determining factors of clinical success in bonding]. PMID- 3333949 TI - [Current status of calcium hydroxide based materials]. PMID- 3333950 TI - [Pulpotomy for the general practitioner: I]. PMID- 3333951 TI - [Dimensional processing changes in M.O.D. type dies in hygroscopic expansion technic]. PMID- 3333952 TI - [Presentation and clinical evaluation of a technic of anterior tooth restoration with vestibular enamel facets adapted from extracted teeth]. PMID- 3333953 TI - [Current status of research and development of a caries vaccine]. PMID- 3333954 TI - [Human acquired immunodeficiency syndrome (AIDS)]. PMID- 3333955 TI - Restoration of an amputated crown by the acid-etch technique. PMID- 3333957 TI - [Examination of the reproducibility of impressions of edentulous mandible performed by several dental prostheticians]. PMID- 3333958 TI - [Prosthetic treatment of edentulous patients with degenerative-productive changes in the temporomandibular joints]. PMID- 3333956 TI - The infected denture: how long does it take? PMID- 3333960 TI - [Individual direct posterior sealing of ready superior complete dentures]. PMID- 3333959 TI - [Buccal stabilizers in inferior complete dentures (preliminary communication]. PMID- 3333961 TI - [Effect of the preparation Dentin Adhesit on the connections of phosphate cement and polycarboxyl cement and MF Heliosit resin with dentine]. PMID- 3333962 TI - [Improvement of the conditions of the maintenance of a total prostheses using a modified occlusal impression]. PMID- 3333963 TI - [The effect of Dentin Adhesit preparation on the adhesion strength of composites in contact with dentin]. PMID- 3333964 TI - [Materials used for fixation of AET prosthetic bridges]. PMID- 3333965 TI - [Investigations for determination of the resistance of composite material binding to chromium-cobalt alloys of AET bridges]. PMID- 3333966 TI - [Considerations and proposals concerning the treatment of patients after maxillary resection]. PMID- 3333967 TI - [The condition of prosthetic replacement and the need for prosthetic treatment in a selected group of elderly patients]. PMID- 3333969 TI - [Prosthetic rehabilitation treatment of three patients with tissue loss after operations for neoplasms]. PMID- 3333968 TI - [Requirements for prosthetic treatment in operators of heavy self-propelled machines working in the Legnica-Glogow copper mining region]. PMID- 3333970 TI - [Height of cusps of artificial teeth and the their effect on the static position of prostheses and masticatory efficiency]. PMID- 3333972 TI - [The durability of the connections of Mifam Super Lux and Milacril teeth with acrylic plate]. PMID- 3333971 TI - [Functional adherence by suction]. PMID- 3333973 TI - [The subperiosteal implant in the rehabilitation of the unilateral or bilateral free and partially edentulous patient (preliminary communication)]. PMID- 3333974 TI - Immunodeficiency associated with malaria. PMID- 3333975 TI - [Distribution and natural infection index of triatominae captured in the Campinas region, Sao Paulo, Brazil]. PMID- 3333977 TI - [The compensatory curve in complete dentures]. PMID- 3333976 TI - [Home ecology of trypanosomiasis americana: feeding profile of Triatoma infestans in a rural area of the Santiago del Estero province, Argentina]. PMID- 3333978 TI - [Fluoride application by dentin desensitizing electrophoresis]. PMID- 3333979 TI - [Sequential restoration of fractured anterior teeth without using the fragment. Clinical case]. PMID- 3333980 TI - [A proposed impression technic for the completely resorbed lower ridge]. PMID- 3333981 TI - [Transient bacteremia from anaerobic microorganisms after suture removal]. PMID- 3333982 TI - [Intracanal medications]. PMID- 3333983 TI - [Conceptual change from magic sleep to psychosomatic sleep]. PMID- 3333984 TI - [Current status of the therapy of anterior cruciate ligament injuries]. AB - This review presents the current concepts in the treatment of anterior cruciate ligament (ACL) injuries. Conservative treatment emphasising strengthening of the muscles to stabilise an unstable knee is discussed. The agonistic and antagonistic functions of the hamstrings and the quadriceps muscle in relation to the ACL are described. The possible mechanisms of muscular stabilisation of the knee are discussed on a neurophysiological basis. The existence of joint specific receptors is pointed out and their reflex and perceptive functions are demonstrated. Taking this into account one can deduce a two-step mechanism of joint protection: 1) via the mechanical strength of the joint capsule and ligaments and 2) via reflex muscle contractions. It follows therefrom that in an unstable knee with a lax capsule and disturbed reflex mechanisms, strengthening of muscles alone is insufficient and cannot protect the joint from progressive deterioration. Therefore, surgical treatment is necessary for an ACL deficient knee. Our indications for ACL reconstruction are described. In addition, the existing methods of surgical replacement of the ACL are critically elucidated. In our opinion, an extraarticular repair tendon transfer as the only surgical procedure to regain stability is of only historical interest. However, extraarticular repair of the medial or lateral capsule is often a necessary additional step to restore stability of the knee. The replacement of the ACL is the crucial step. Using autogenous grafts one must consider the doubtful outcome of biological response leading to necrosis and revascularization in the transplant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3333985 TI - [Conservative functional treatment of fibular capsule ligament rupture even in the performance athlete?]. AB - In a prospective randomised study we examined 80 men and women of 18 to 45 years of age and 40 competitive sportsmen and sportswomen with fresh ruptures of the talofibular and calcaneofibular ligaments treated either surgically or conservatively by functional bracing. We controlled the results by anamnesis and by clinical and radiological follow-up. Conservative treatment leads to the same results after 3-8 months as surgical treatment (5 +/- 2 degrees of talar angulation). Functional conservative treatment results in earlier painless weight bearing in comparison to the surgical treatment which was, however, combined with three weeks immobilization directly after surgery. This proves the superiority of the early functional conservative treatment as long as there are no bony capsuloligamentous tears, osseocartilaginous lesions of the joint surface with splintered-off chips or "flakes" of cartilage ("flake fractures") or reruptures of a chronically unstable ankle joint. The similarly good results achieved in the group of 40 sportsmen and sportswomen by early functional conservative treatment do not justify operation of ruptures of the talofibular and calcaneofibular ligaments. PMID- 3333986 TI - [Morphology of human skeletal muscle and its adaptability to different training conditions]. AB - Endurance exercise training improves the oxidative capacity of the muscles directly involved in training. Structurally we find an increase in capillary supply and an enlargement of the mitochondrial compartment of muscle fibers. In contrast, strength training increases the muscle fiber's content of contractile proteins at the expense of the oxidative structures. Both types of training enhance substrate content of muscle fibers. In strength training we find more glycogen, in endurance training more lipids and more glycogen in trained muscle fibers. PMID- 3333987 TI - [Ultrasound diagnosis of soft tissue injuries of the locomotor system]. AB - We report on our first experience with ultrasonography in soft tissue lesions. The normal and pathological anatomy of the shoulder joint, knee joint, achilles tendon and muscle is demonstrated. The technical equipment of real-time sonography is demonstrated. PMID- 3333988 TI - [Sonography of Achilles tendon changes in athletes]. AB - Sonography of the achilles tendon is a sure diagnostic method. It allows to recognise different pathological changes in the tendon. In a screening study we performed sonography of 156 achilles tendons in 78 sportsmen. We found a correlation between the results of clinical investigations, pain and sonographic findings. In some cases sonography showed structural changes in the achilles tendon without subjective complaints in the patients. Besides the pathological changes of the achilles tendon we observed an increasing caliper and echo density of the tendon in elderly patients. The delineation of the achilles tendon against the surrounding tissues was superior in younger patients. Disorders of the achilles tendon which had occurred in the patients on a previous occasion resulted in structural changes of the tendon in 75% of the cases, retrospectively identified by ultrasonography. PMID- 3333989 TI - [Experimental and clinical results of ultrasound imaging in sports orthopedic soft tissue diseases]. AB - Ultrasound scanning of the shoulders, knee joints, Achilles' tendon and muscles is presented as a noninvasive technique for the diagnosis of joint and soft tissue disorders. In experimental ultrasound studies on shoulders, knee joints, tendons and muscles of cadavers the diagnostic value of the method is assessed. The experimental observations were compared with clinical results collected in three years from 610 patients. Particularly characteristic findings in sports induced soft tissue lesions are reviewed as examples. PMID- 3333990 TI - [Autotransplants. Review of the literature and a clinical case]. PMID- 3333991 TI - [Complete cast crowns for deciduous or young permanent teeth--direct technic]. PMID- 3333992 TI - [Prosthetic rehabilitation of a patient with hemi-mandibulectomy and partial glossectomy]. PMID- 3333993 TI - [Some reflections on rehabilitation with oromaxillofacial prostheses]. PMID- 3333994 TI - [Autotransplants. Review of the literature and a clinical case]. PMID- 3333996 TI - [Current considerations on Sjogren's syndrome]. PMID- 3333995 TI - Surgical technique of Bioceram sapphire dental implants--screw type. PMID- 3333998 TI - [Skeletal prosthesis fabrication technic--step by step]. PMID- 3333997 TI - [Enamel preparation for acid etching]. PMID- 3333999 TI - [White lesions of the mouth]. PMID- 3334000 TI - [Non Q infarct: diagnostic and prognostic risks]. PMID- 3334001 TI - [Disabling respiratory diseases: sociomedical and organizational problems]. PMID- 3334002 TI - [Respiratory system and environmental noxiousness]. PMID- 3334004 TI - Graft-induced polyclonal activation of B cells. I. Alloantigen-induced humoral response in mice. AB - In recent years evidence has accumulated pointing out that graft rejection may be mediated not only by cellular but also humoral mechanisms. To study this problem in some detail, humoral responses were studied in mice subjected to skin grafting across the H-2 locus. B cell reactivity was measured during the first and second set reactions on consecutive days after transplantation until graft rejection. In vitro B cell activity was assessed by means of the reverse plaque-forming cell assay (PFC) using cells obtained from the lymph nodes and spleens. The results indicate that polyclonal activation of B cells is an integral part of the immune response to skin transplantation in mice. However, no correlation was found between the level of activation as demonstrated by the PFC and the time of graft rejection. PMID- 3334003 TI - [Pulmonary hypertension in chronic obstructive bronchopneumopathy (COBP): possible role of platelets]. PMID- 3334005 TI - Graft-induced polyclonal activation of B cells. II. Humoral response of renal allograft recipients (RAR). AB - Ig production by peripheral blood lymphocytes of renal allograft recipients was studied. It was demonstrated that lymphocytes of patients with acute graft rejection produce elevated numbers of PFC in culture in response to PWM (a T-cell dependent stimulus) and Salmonella paratyphi B (a T-cell independent stimulus) as well as spontaneously. PFC responses were significantly higher in patients with acute rejection than in a group of patients with stable graft function. The B cells of the recipients with stable graft function showed a normal humoral response in vitro. During chronic rejection no significant changes were found in the production of antibodies by B cells. PMID- 3334007 TI - Some biological properties of outer membrane proteins of Shigella. AB - Outer membrane proteins (OMP) derived from two antigenically different representatives of Shigella (Sh. flexneri 3a and Sh. sonnei phase I) were tested for the toxicity, pyrogenicity, ability to induce Shwartzman reaction as well as for their influence on the leukocyte system. LD50 dose determined on mice was 28 mg/kg for OMP of Sh. flexneri and 23 mg/kg for OMP of Sh. sonnei. Both preparations injected intravenously to rabbits caused moderate increase of body temperature, expressed by the value 1.8 degrees C. Intravenous administration of protein preparations to rabbits, induced at first leukopenia and then transient leukocytosis. When injected subcutaneously in the dose of 500 micrograms and after 24 h intravenously in the dose 100 micrograms, they produced slight hemorrhagic changes at the site of administration. PMID- 3334006 TI - Disorders of the lymphatic homing and MIF production by the lymphocytes of thymus, spleen and lymph nodes after liver injury caused by portocaval shunt in rats. AB - This paper presents the quantitative changes and disorders in migratory inhibition factor (MIF) production by thymus, lymph node and spleen cells after liver injury provoked by the porto-caval shunt (PCS) in rats. The great depopulation of the lymphatic organs, particularly the thymus, was demonstrated. The reduction of MIF generation after PCS was also noticed. The severe liver injury reflected by high activity of GOT and GPT was observed on the second day after surgical procedure. Our investigations bring into light the multifold interrelationships between the functionally efficient liver and lymphatic organs in rat. PMID- 3334008 TI - Pen injury: a rare complication. AB - An 18-month-old male sustained an intra-oral injury after falling on a pen. The internal carotid artery was occluded without evident neurologic deficit. The pen tip was surgically removed from the cerebellum. PMID- 3334010 TI - Congenital alopecia, seizures, and psychomotor retardation in three siblings. AB - Three siblings, devoid of hair at birth, had an unusual autosomal recessive disorder characterized by universal congenital alopecia, microcephaly, seizures, psychomotor retardation, and severe growth failure. Metabolic and chromosome studies were normal. Skin biopsies disclosed immature hair follicles, some of which were filled with keratotic material but had no hair shafts. Neuropathologic features included cerebral cortical hypoplasia, neuronal depletion, and microcalcifications. The familial occurrence of universal congenital alopecia conjoined with nonprogressive central nervous system abnormalities in this and other kindreds defines a nosologic group of neurocutaneous disorders in which congenital alopecia is the solitary cutaneous manifestation. PMID- 3334009 TI - Brain death in children: Part I. AB - The determination of brain death during childhood has become increasingly important and in some ways controversial. This initial article reviews historical data and guidelines and provides a perspective for the recommendations which will be discussed in the second article (Part II). PMID- 3334011 TI - Brain death in children: Part II. AB - The determination of brain death in children has increasingly relied on a variety of neurodiagnostic studies to confirm the clinical diagnosis. This second article on brain death reviews the relevant pediatric electroencephalographic, evoked response, and cerebral blood flow studies, provides our recommendations and protocol for the determination of brain death in children, and considers some of the problems associated with physiologic stabilization of the brain dead child who is considered for organ donation. PMID- 3334012 TI - Attention deficit disorder: current perspectives. AB - This review focuses on selected issues in the rapidly proliferating scientific literature on attention deficit disorder (ADD). It encompasses a brief overview of ADD, including a review of the historical trends, causation, and a description of the clinical characteristics. Critical issues fundamental to understanding of ADD are addressed next. Evidence is presented to suggest that there are several groups of children with ADD who are currently under-identified and therefore, underserved (girls with ADD; ADD without hyperactivity). The concept is introduced of uncomplicated ADD and ADD-Plus (ADD-P), a term used to designate ADD associated with other complicating features such as conduct disorder. Specific methodologic issues and their relationship to the under-identification of these groups of children follows. This discussion encompasses the reasons for diagnostic imprecision and inconsistency, emphasizing the problem of selective referral patterns and how it results in an inaccurate portrait of ADD. We then present new approaches to the definition and diagnosis of ADD based on empiric studies designed to circumvent some of these problems. We conclude with a summary of the implications of these findings, and recommendations for public policy in ADD, particularly the need to recognize that ADD may occur even in the most intellectually gifted individuals and even in students in select colleges. Often these children with the highest potential are penalized most, not because of conceptual limitations or because they do not understand, but because educators often fail to recognize the symptom complex. Many of these children are succeeding through intelligence and great effort, but many more could succeed with proper identification. PMID- 3334013 TI - Post-infectious leukoencephalopathy as a complication of Mycoplasma pneumoniae infection. AB - We report a 9-year-old girl with leukoencephalopathy who demonstrated serologic evidence of a Mycoplasma pneumoniae infection. She had a mild upper respiratory tract illness 10 days prior to admission and developed walking difficulty and somnolence. The neurologic symptoms progressed to semicoma and spastic paraplegia over a few days but began to improve on the fourth day. Cranial computed tomography on the eleventh day revealed an area of diffuse low density in the white matter. Cerebrospinal fluid examination was normal. The patient recovered with minimal motor deficits. Cranial computed tomography was normal. She was diagnosed as having leukoencephalopathy complicated by a Mycoplasma pneumoniae infection. The pathogenesis of this infection is believed to be an allergic reaction to Mycoplasma pneumonia of the central nervous system as well as an acute disseminated encephalomyelitis. PMID- 3334014 TI - Citrobacter diversus and neonatal brain abscess. AB - A 23-day-old infant presented with apnea and was found to have Citrobacter diversus meningitis and brain abscess. The organism persisted in brain abscess fluid for over 4 weeks despite adequate antibiotic therapy. Cranial computed tomography demonstrated persistent radiolucencies in both frontal lobes, and midline shift, long after completion of antibiotic therapy. Effective therapy of C. diversus meningitis and brain abscess may require use of an antibiotic active within phagocytes, and judicious surgical drainage. A high prevalence of brain abscess mandates cranial computed tomography for any infant with C. diversus meningitis. PMID- 3334016 TI - Superior sagittal sinus thrombosis in neonates. AB - Three neonatal patients with superior sagittal sinus thrombosis are reported. The neurologic signs were bulging of the anterior fontanel and clonic hemi convulsions. Neonatal polycythemia was believed to be an etiologic factor in two patients. Computed tomography revealed massive edema with slit-like ventricles in two patients. Increased density of the torcular Herophili and straight sinus also were demonstrated in two patients. The diagnosis of superior sagittal sinus thrombosis was confirmed by cerebral angiography in one patient and by digital subtraction angiography in the other two patients. Digital subtraction angiography appears to offer a definite advantage in the diagnosis of cerebral sinus thrombosis in the neonatal period. PMID- 3334015 TI - Somatosensory evoked potentials: Part I. A review of neural generators and special considerations in pediatrics. AB - Despite the recognition of evoked potentials in the late nineteenth century and the recording of somatosensory evoked potentials (SEPs) in 1947, there still is much to be learned about the origin of the SEP and its applications, particularly in the field of pediatric neurology. We summarize relevant data from the literature concerning the neural sources and present the currently accepted generators of the various peripheral, subcortical, and cortical components. The importance of factors such as growth, maturation, and the effects of sedation and sleep are discussed. The clinical applications of SEPs in pediatric neurology will be presented in Part II. PMID- 3334017 TI - Acquired paroxysmal movement disorders. AB - Acquired paroxysmal movement disorders are reported less frequently than the familial forms of paroxysmal dyskinesias. Three children, with the acquired form of the disorder which followed an early childhood encephalopathic event, are described. Three similarly affected children have been reported previously. Movement disorders developing after perinatal encephalopathy appear to be a distinct entity. Patients with this condition demonstrated clinical improvement following the initiation of antiepileptic medications. PMID- 3334018 TI - Recurrent and pre-eruptive acute cerebellar ataxia: a rare case of varicella. AB - This is a report of an unusual case of acute cerebellar ataxia in which the ataxia recurred after a 6 week interval and the second episode of ataxia antedated the varicella exanthem by 19 days, suggesting the direct invasion of the central nervous system by the varicella virus. PMID- 3334019 TI - Somatosensory evoked potentials: Part II. A review of the clinical applications in pediatric neurology. AB - Fundamental to the clinical application of somatosensory evoked potentials is an understanding of the neural generators, the changes in disease states, and the effects of growth and maturation; aspects relevant to pediatric somatosensory evoked potentials were discussed previously (Part I). The importance of establishing normative data across age- and size-matched controls in the pediatric population, however, cannot be overstated. The following review of the clinical applications of somatosensory evoked potentials in pediatric neurology is based on a review of the literature and on the experience gained from over 900 studies performed in our laboratory during the last 4 years. PMID- 3334021 TI - Rectal administration of antiepileptic drugs in children. AB - This article reviews the current literature describing the use of rectally administered antiepileptic drugs. Individual antiepileptic drugs are discussed in regard to efficacy, toxicity, and rate of absorption. Absorption occurs through passive diffusion; therefore, solutions are absorbed most quickly. Paraldehyde, diazepam, secobarbital, and valproic acid are used when rapid effect for termination of prolonged or serial seizures is desired. Valproic acid, lorazepam, carbamazepine, and phenytoin all can be used for maintenance therapy. PMID- 3334020 TI - Fragile X syndrome in Japanese patients with infantile autism. AB - Forty-seven patients (39 boys and 8 girls) with infantile autism whose clinical symptoms had matched the diagnostic criteria of DSM III were studied cytogenetically for the occurrence of fragile X [fra(X)] syndrome. The existence of fra(X) chromosome in these patients was screened first by culturing peripheral blood lymphocytes in a medium in which folic acid was absent; the fra(X) chromosome then was confirmed by reculturing in another medium to which 5-fluoro 2'-deoxyuridine was added for the last 24 hours of culture. Fra(X) chromosome was found in 2 of 39 male patients, but in none of the female patients; the 2 patients are siblings. Thus, fra(X) syndrome occurs in 2.6% (1/38) in this study population of male autistic children. The frequencies of fra(X) expression in the older brother with mild mental retardation, in the more severely retarded younger brother, and in their mother were 3-5%, 17-20%, and 9-3%, respectively. Of the two methods used in the present study, the method employing 5-fluoro-2' deoxyuridine tended to be more sensitive to fra(X) chromosome detection, especially for a suspected carrier. PMID- 3334022 TI - Dominantly inherited congenital cerebellar ataxia with atrophy of the vermis. AB - We report a mother and daughter with congenital cerebellar ataxia and normal intelligence. Computed tomography revealed localized atrophy of the cerebellar vermis. This is the second case report of dominantly inherited, nonprogressive, congenital cerebellar ataxia. PMID- 3334023 TI - Cervical spinal stenosis with cord neurapraxia and transient quadriplegia. AB - Cervical spinal cord neurapraxia with transient quadriplegia is defined as a distinct clinical entity. The authors identify diminution of the anteroposterior diameter of the spinal canal as the factor that explains the described neurologic picture of the injury. Based on the result of a study of 39,377 athletes, the authors conclude that the prevalence of the injury is high and warrants attention. Given that of the patients interviewed, none recalled prodromal experience of transient motor paresis and none sustained further injury, this injury does not predispose individuals to permanent neurologic injury. No definite recurrence patterns have been established that would warrant the restriction of individuals from further activity. Activity restrictions are called for in the case of individuals with stability or chronic degenerative changes. Individuals with developmental spinal stenosis or spinal stenosis should be treated on an individual basis. PMID- 3334024 TI - Intracranial injuries resulting from boxing: a review (1918-1985). AB - A review of the available records indicates that there have been a substantial number of fatalities in boxers due to intracranial injuries sustained in the ring in comparison to the numbers engaged at both amateur and professional levels. The number of such fatalities has decreased steadily in recent years owing to different measures taken by boxing authorities to decrease the physical hazards in the ring and to improve monitoring of boxers during bouts by referees and physicians. The considerable concern about the long-term effects of repeated brain injury as the result of boxing in producing chronic encephalopathy is adequately justified by the many studies of live boxers and pathologic examinations of brains of former boxers made and recorded over the years since 1952. These indicate clearly a significant relationship between the numbers of bouts fought and the presence of severity of chronic encephalopathy. Because it is unlikely that currently adopted protective measures will substantially reduce these hazards, even though they have apparently reduced direct fatalities, a reasonable approach to prevention would be to reduce the number and severity of blows to the head. This might be done by making any blow to the head in boxing a foul and a reason for disqualification. Another approach would be the elimination of boxing. PMID- 3334025 TI - Boxing injuries: neurologic, radiologic, and neuropsychologic evaluation. AB - Boxing is an endeavor that may have to be re-evaluated in the coming years as to whether it should be designated as a sport. It is the only "sport" in which victory is determined by the amount of physical damage done to the opponent. We have presented the largest number of professional and amateur boxers (58) evaluated by various modern diagnostic modalities and have unequivocally demonstrated the deleterious effects of boxing upon the brain. There have been few, if any, meaningful actions taken by the promoters of boxing to correct the conditions under which boxers are subjected to physical abuse. Recommendations regarding the creation of a National Board of Boxing to supervise this "sport" have not been heeded. Suggested safeguards for the boxer, including mandatory medical and boxing history records (passports), use of headgear and approved safe boxing gloves, avoiding blows to the head, improved boxing ring floors, mandatory neurologic examinations, and more competent physicians at ringsides making medical decisions, have essentially not been implemented. The suggestions that mandatory computed tomograms at various stages in a boxer's career be used to determine possible changes of atrophy have not been followed, even when the CT scans have been made available at no cost to the boxers. The effective use of neuropsychologic evaluation, even when offered at no cost, has also been denied. The established medical injuries due to boxing and the lack of any sustained and significant efforts on the part of organized boxing create an atmosphere that is conducive to following the call for the consideration of a ban of boxing. PMID- 3334026 TI - Trampoline-induced quadriplegia. AB - This review of the world's literature documenting cervical spine injuries attempts to determine common factors regarding patient characteristics, environment, injury mechanisms, and pathology. The policy statements and safety guidelines of both the American Academy of Pediatrics and athletic administrative bodies are reviewed in order to evaluate what effect, if any, these policies and guidelines have had on documented injuries. On the basis of this review, it is believed that the AAP was ill-advised in altering its position on the use of trampolines. The opinion is presented that both the trampoline and minitrampoline are dangerous devices when used in the best of circumstances, and their use has no place in recreational, educational, or competitive gymnastics. PMID- 3334027 TI - The unheralded value of arthroscopy using local anesthesia for diagnostic specificity and intraoperative corroboration of therapeutic achievement. AB - The senior author has performed more than 600 "therapeutic" arthroscopies under local anesthesia since 1978. The authors believe that the cases presented illustrate the increased diagnostic accuracy offered by performing arthroscopy of the knee under local anesthetic in certain types of cases. We are by no means advocating that all arthroscopies of the knee be performed under local anesthesia. Certainly, the majority of knee arthroscopies need not be performed under local anesthesia, because the diagnosis is usually evident. Perhaps when the diagnosis is not clear, a combination of local with regional or with general would be best, with performance of the diagnostic portion of the arthroscopy under local anesthesia. When an instantaneous improvement is possible, such as change in joint motion, or when some change in joint dynamics may be visualized, local should then be continued through the therapeutic conclusion of the procedure. Arthroscopy under local anesthesia has also been performed by the authors on the shoulder, elbow, and ankle, where the diagnostic benefits have been realized. Certain reconstructive operations, such as patellar realignments, are worthy of performance under local anesthesia in selected cases. In conclusion, the authors believe that arthroscopy of the knee and other joints under local anesthesia may add measurably to the diagnostic capability of the arthroscopist, and not infrequently to a therapeutic advantage. PMID- 3334028 TI - The perioperative management of the arthroscopic patient. AB - This article has described the perioperative management of the arthroscopic patient. As emphasized, preoperative planning requires a precise diagnosis, patient education, and selective procedures. The operative management is sophisticated, exacting, and challenging, as discussed in other articles of this issue. Finally, the postoperative management is specifically directed toward pathology and procedure. Recovery times are variable, and complications are not insignificant and can lead to prolonged patient morbidity and financial loss. It is important to consider patient goals versus reality, patient willingness to opt for acceptable versus optimal results, and if the procedure is necessary versus justified versus contraindicated. If all of these factors are kept in mind by the surgeon and conveyed to the patient, arthroscopic surgery can be extremely rewarding to both. PMID- 3334030 TI - Arthroscopic anterior cruciate ligament reconstruction. AB - Our understanding of the structure and function of the anterior cruciate ligament has progressed rapidly over the past decade. Arthroscope-assisted anterior cruciate ligament replacement is a new procedure that allows isometric placement of the anterior cruciate ligament graft. Postoperative rehabilitation is enhanced by preservation of the extensor mechanism. PMID- 3334029 TI - Arthroscopy of the ankle. AB - This article describes the surgical technique of arthroscopy of the ankle and the indications for its use. In addition to describing the common anterolateral and anteromedial arthroscopic portals, a discussion is also given regarding portal anatomy of ankle arthroscopy and the various neurovascular structures that lie in close proximity to the arthroscopic portals. Arthroscopy of the ankle has a definite role in the management of certain lesions of the ankle, such as loose bodies, or osteochondral or chondral defects of the talus. Ankle arthroscopy is a technically demanding surgical procedure and great attention to detail is required to perform this procedure in a safe and reproducible fashion. PMID- 3334031 TI - Arthroscopic meniscal repair. AB - Arthroscopic meniscal repair is a promising new technique for treating peripheral meniscal tears. With proper attention to surgical technique, the repair can be safely performed by any surgeon with moderate arthroscopic skills. We recommend that in all cases the capsule be exposed through a small incision to identify and protect the neurovascular structures. When an associated ACL tear is present, ligamentous reconstruction is also recommended. Although we currently limit our repairs to peripheral tears, newer techniques may expand indications for this procedure. PMID- 3334032 TI - Motion-limiting arthrofibrosis of the knee: the role of arthroscopic management. AB - With the advent of effective arthroscopic methods of intra-articular surgery, it has become possible to lyse intra-articular adhesions under direct vision using arthroscopic techniques. This article reviews the present indications for this procedure, the techniques, the methods of after-care, and the reported results. Previous studies and an additional series of patients are reviewed. PMID- 3334033 TI - Wrist arthroscopy. AB - Understanding of wrist biomechanics and pathology is enhanced by wrist arthroscopy. The procedure does indeed provide an alternative to arthrotomy in selected situations, greatly decreasing patient morbidity. It is a difficult skill to acquire; however, wrist arthroscopy presents diagnostic and therapeutic benefits that far outweigh this short-lived drawback. PMID- 3334034 TI - Elbow arthroscopy. AB - Decreased surgical morbidity and rapid recovery time associated with arthroscopic surgery of the elbow justify its preference over more extensive open incisions in selected cases. Not all elbow conditions can be treated arthroscopically, however, and open incisions are still preferred in more extensive problems such as displaced fractures and olecranon impingement syndromes. PMID- 3334035 TI - Shoulder arthroscopy in the throwing athlete: perspectives and prognosis. AB - The efficacy of arthroscopy of the shoulder has been demonstrated as both a diagnostic and an operative tool. The throwing athlete has benefited greatly from this procedure. Intra-articular pathology resulting from throwing motion overuse can be visualized and treated, with relatively little morbidity and a rapid rehabilitation phase. PMID- 3334036 TI - The arthroscopic treatment of subacromial impingement. AB - In order to effectively employ arthroscopic techniques for a subacromial decompression, a thorough understanding of the impingement syndrome and its clinical manifestations is necessary. The authors' preliminary experience with the arthroscopic subacromial decompression suggests excellent results with early return to competitive athletics. PMID- 3334037 TI - Arthroscopic stabilization of the anterior shoulder. AB - The arthroscopic stabilization of the shoulder is in its infancy. Soon, improvements in technique and equipment may make it the standard, thus reducing morbidity and time loss from full function. PMID- 3334038 TI - Rehabilitation of the shoulder and elbow after arthroscopy. AB - Rehabilitation after arthroscopic shoulder and elbow surgery requires an emphasis on flexibility, strength, range of motion, and a return to activity program. Care must be taken to include fitness and conditioning programs for the entire athlete, not just the upper extremity. A thorough program will allow the athlete to return to competition in the best possible condition. PMID- 3334039 TI - Electrosurgery in operative arthroscopy. AB - Electrosurgery is a useful tool in the orthopedic procedures outlined, including lateral release, synovial lesions, and shoulder impingement syndrome. The salient positive characteristic of electrosurgery is the capacity to obtain immediate and thorough hemostasis, thereby allowing the patient to begin a rehabilitative program far sooner than with conventional operative techniques. Less hemarthrosis also lowers the level of postoperative pain and the risk of postoperative infection. By becoming familiar with some of the basics of electrosurgery, including equipment and electrosurgical principles, the surgeon and staff can better utilize electrosurgery and be aware of the potential, yet avoidable, complications. The future appears bright for electrosurgery, with new equipment and procedures being developed, but more research is needed to clarify the long term effects on tissues involved and the clinical results of patients. PMID- 3334040 TI - Current development of instrumentation for arthroscopy. AB - The advances in the field of arthroscopy have been keyed to the development of instrumentation. The most significant innovation has occurred in conjunction with the visualization system itself--cutting instrumentation for resection of soft tissues in bone and, more recently, in joints other than the knee. A brief history of the development of arthroscopic instrumentation is provided in this article. PMID- 3334041 TI - Diving medicine. AB - This article orients the practicing physician to the physical and physiologic basis for the more common medical problems encountered in diving, discusses the common presenting manifestations for these disorders, and provides a framework for their treatment. Medical fitness for diving is also briefly addressed. PMID- 3334042 TI - Medical problems in whitewater sports. AB - Overall, whitewater sports are relatively free of serious medical problems, with submersion accidents, trauma, and overuse syndromes being the most commonly encountered afflictions. Various infectious diseases and environmental exposure problems may occur, but serious illness or injury from such causes is infrequent. Nonetheless, the growing popularity of whitewater sports, along with increasing attempts by less experienced persons to navigate more difficult rivers, underscores the need for physicians to be aware of the medical problems likely to be encountered in these activities so that they may appropriately counsel and prepare persons for these invigorating yet potentially dangerous pastimes. PMID- 3334043 TI - The sun and water sports. AB - Participation in aquatic sports such as sailing, fishing, SCUBA diving, and windsurfing often entails the unavoidable hazard of exposure to high levels of solar radiation. This review discusses what is known about the health hazards of ultraviolet radiation and presents information that allows a rational approach to sun protection. PMID- 3334044 TI - Ophthalmic complications of water sports. AB - Those who participate in aquatic sports are at risk for some special ocular problems. These have been outlined here and include optical problems and refractive errors, pressure related disease, ocular trauma, infections and irritations, toxins, and complications of exposure to sun and wind. Awareness of these disorders may allow better management and prevention. PMID- 3334045 TI - [Clinical specular microscopic analysis of the endothelium of transparent corneal grafts]. PMID- 3334046 TI - Venous drainage of the medial basal segment (S7) of the human left lung. PMID- 3334047 TI - Reduction of Colles' fractures without anaesthesia using a new dynamic bone alignment system. AB - Two techniques for reduction of Colles' fractures were compared in a prospective, randomized study. With use of a newly designed dynamic bone alignment device, reduction manoeuvres were performed on 62 patients with Colles' fractures (group A) without any form of anaesthesia. In a control group of 54 patients (group B) Colles' fractures were reduced manually in the traditional way using local infiltration anaesthesia. In each group the pain experienced by the patients was recorded. Severe pain during the reduction was reported by 8 per cent of the patients in group A and by 35 per cent of those in group B. No complications occurred during or after dynamic reduction without anaesthesia. This method of treatment seems to be a very gentle one for the patients, with the advantage of causing less pain than treatment under local anaesthesia. PMID- 3334048 TI - Splenic injury--a prospective multicentre diagnostic study. AB - One hundred and forty-seven patients with splenic injury were entered in a prospective multicentre study including 18 hospitals. The diagnosis was made by scintigraphy in 55 patients, ultrasonography in 51 and computed axial tomography in 31. Exploratory laparotomy was performed in 52 patients, in 23 of these after a positive peritoneal lavage. Splenic injury was found in 33 per cent of the ultrasound examinations, indicated in another 20 per cent and not indicated in 16 per cent. In 31 per cent increased intraperitoneal effusion was the only finding. There was a tendency towards an underestimation of the injury by ultrasonography. Peritoneal lavage was positive in all examinations. PMID- 3334049 TI - The occurrence, structural and functional properties of immunoglobulin Fc receptors on murine neoplastic cells. PMID- 3334050 TI - Host-tumor interactions in the SJL lymphoma model. PMID- 3334051 TI - Therapeutic strategies for B cell malignancies involving idiotype-anti-idiotype interactions. AB - The therapeutic use of unmodified monoclonal anti-idiotypic antibody for human B cell malignancies has met with limited success. Some factors thwarting antibody attack can be identified, such as the presence of extracellular idiotypic immunoglobulin (Ig), and the escape of the target cell by antigenic modulation. Another possibility is a change in idiotypic determinants due to somatic mutation. For direct attack on tumor cells in vivo it might be necessary to use antibody derivatives: univalent antibodies will avoid modulation, and chimeric univalent antibodies consisting of mouse Fab' gamma linked to host Ig of appropriate subclass can be engineered to mediate particular effector functions while reducing immunogenicity. Another approach is to use toxin or isotope bearing antibodies. However, the final eradication of tumor might involve the natural non-specific, and specific anti-idiotypic mechanisms of the host which should not be damaged by antibody therapy, and which appear to be involved in control of tumor progression in patients in long-term remission. Rapidly growing animal lymphomas presently available as models cannot mimic more than a small fraction of human lymphoma but they provide useful information for design of passive anti-idiotype therapy. However host anti-idiotypic immunity must be induced in such models by pre-immunization with purified idiotype. Such a procedure can generate effective anti-idiotypic immunity which is highly protective in mouse and guinea pig lymphomas. Analysis of mechanisms involved should give insight into the role of the idiotype networks in the behavior of human disease. PMID- 3334052 TI - Components of immune function studied with lymphoid tumors. AB - Lymphoid tumors have proven to be productive models for investigating genetic, biochemical, physiological and developmental mechanisms of lymphoid cells. Lymphoid tumors of a given lineage exhibit a spectrum of phenotypes from clones whose features overlap extensively with their normal counterparts to clones whose features are not obviously represented in normal lymphoid populations. In addition to the phenotypic continuum represented in a library of related tumors, many clones exhibit phenotypic diversity spontaneously or in response to various stimuli. As laboratory technology has advanced many interesting biological features of lymphoid tumors have become amenable to precise analysis. Progress made in understanding the mechanisms that underly the phenotypic diversity and plasticity of lymphoid tumor cells has the dual impact of improving our knowledge of malignant and normal lymphoid cells. PMID- 3334053 TI - Liposomes for paramagnetic contrast enhancement in n.m.r. imaging. PMID- 3334055 TI - Calcium antagonists and the kidney. AB - Calcium antagonists are frequently used to treat patients with hypertension or ischaemic heart disease. These patients often have renal impairment, so the effects of calcium antagonists on the kidney are important. The effects of calcium antagonists on renal haemodynamics are variable and depend on the state of the patient or animal and the dose of calcium antagonist used. Calcium antagonists cause natriuresis and diuresis by a mechanism which is not fully understood, but which is probably not directly due to the effects of calcium antagonists on renal haemodynamics. The diuretic effect may be useful in limiting the oedema which would otherwise be induced by vasodilator therapy. The effects of calcium antagonists on peripheral renin activity are unpredictable: renin release may be affected directly, as well as via haemodynamic effects. The pharmacokinetics of calcium antagonists are little changed in renal failure, since these drugs are metabolised in the liver. Calcium antagonists appear to be safe and useful treatments for patients with hypertension or ischaemic heart disease and co-existing renal impairment. PMID- 3334054 TI - The use of captopril and captopril plus frusemide as antihypertensive agents in non-insulin dependent diabetes. AB - After all previous antihypertensive treatment had been stopped, blood pressure and glucose tolerance were measured in 16 hypertensive non-insulin treated diabetics before and again six weeks after treatment with captopril, an angiotensin-converting enzyme inhibitor. Supine blood pressure fell from 184 +/- 4.1/103 +/- 2.6 to 165 +/- 5.2/88 +/- 2.1 mmHg (P less than 0.001) and erect from 179 +/- 5.2/102 +/- 3.2 to 158 +/- 5.6/87 +/- 2.6 mmHg (P less than 0.005). The area under the oral glucose tolerance curve fell from 2313.6 +/- 154 to 2192.8 +/ 146 mmol/min/l (P less than 0.02). There was no change in plasma insulin, total glycosylated haemoglobin or fructosamine. Four patients who failed to show lowering of supine diastolic pressure below 95 mmHg were additionally given oral frusemide with further improvement in blood pressure and no alteration in carbohydrate intolerance. It was concluded that captopril alone is usually an effective antihypertensive agent in non-insulin dependent diabetes with the addition of frusemide benefiting resistant cases. Glucose intolerance did not worsen with either captopril alone or captopril plus frusemide. PMID- 3334056 TI - Nifedipine and acebutolol in combination for the treatment of moderate to severe essential hypertension. AB - In a randomised, crossover study of patients with moderate to severe essential hypertension, the effects of the calcium entry antagonist nifedipine and the beta receptor blocking drug acebutolol were studied on their own, and in combination. After 4 weeks of nifedipine tablets 20 mg twice daily (Adalat, Bayer), mean supine blood pressure (BP) fell by 20 mmHg and after 4 weeks of acebutolol 200 mg twice a day (Sectral, May & Baker) by 11 mmHg. When nifedipine and acebutolol were given in combination in the above doses for 4 weeks, there was a significantly greater fall in BP than with either agent alone, supine mean arterial pressure falling by 27 mmHg. The above BPs were measured 2 h after the last dose of tablets. Measurements 12 h after the last dose showed smaller falls in BP, with a significantly greater fall with combination treatment than with acebutolol alone. The fall in BP 12 h after the last dose of the combination was greater than with nifedipine alone but this difference was not statistically significant. This randomised, controlled study showed that nifedipine and acebutolol have a marked additive effect on BP which is sustained for at least 12 h after treatment. PMID- 3334057 TI - Canine transmissible venereal tumor (TVT): a review. AB - The occurrence, transmission, clinical appearance, histological findings, chromosome studies, immunity, different methods of treatment and the prevention of canine transmissible venereal tumour are reviewed. PMID- 3334058 TI - Bacteremia in adult men. AB - A prospective study was done to characterize positive blood cultures in adult male veterans. The research included 277 patients over a 15-month period. There were 348 organisms isolated, of which 65 percent were pathogens, 6 percent probable pathogens, 4 percent probable contaminants, and 25 percent contaminants. The most common isolates were coagulase-negative staphylococci (23 percent), Escherichia coli (12 percent), Klebsiella pneumoniae (10 percent), Staphylococcus aureus (9 percent), Streptococcus pneumoniae (6 percent), and Pseudomonas aeruginosa (5 percent). The number of positive blood cultures was significantly greater for pathogens (mean 1.8 bottles) than contaminants (mean 1.2). Patients with pathogens were more likely to have hypotension than those with contaminants. At least 40 percent of all patients with a positive blood culture died within 14 days after their first positive culture. The vast majority of bacteremias were community acquired. As lungs and wounds comprised about one half of the sites of entry for the bacteremias, it appears that more emphasis should be placed on early diagnosis and efficient treatment of infections from these sites to reduce subsequent mortality. PMID- 3334060 TI - A review of the treatment of cancer of the male breast with a case follow-up. AB - The author presents a four-year follow-up of a male patient with cancer of the breast. The lesion was large, fungating, and ulcerating. It was treated effectively with cobalt without mastectomy. PMID- 3334059 TI - Neurologic complications of the acquired immune deficiency syndrome. AB - The acquired immune deficiency syndrome (AIDS) is a syndrome requiring unique knowledge of its versatile manifestations for accurate diagnosis and skillfull management of its numerous complications for successful treatment. The human T cell lymphotropic virus type III (HTLV-III), a replication-complete virus, is now reported as the etiologic agent. The neurologic complications of AIDS cover the spectrum of neurologic diseases and usually have multiple causative factors, all of which should be appropriately managed. These complications can be successfully treated, although constant monitoring is required because recurrence is frequent. The neurologic complications are the second most frequent cause of death in AIDS patients.Tests that are usually reliable in diagnosing neurologic diseases may not be reliable in patients with AIDS. The management of AIDS is a multidisciplinary effort, and the neurologist should fulfill a role in the management team. PMID- 3334061 TI - A legislative agenda for health: 1987 to 1992. AB - Health policy issues in the 1980s have been influenced largely by fewer federal dollars and by the increasing prominence of the private sector. As a result, several indicators of health status, especially among the poor, have deteriorated. The 1986 election and the return of Democratic Party control of the US Congress provides opportunities to seek to restore and increase funding in several areas and to develop new policy initiatives. Recommendations for funding and new health policy initiatives in the areas of AIDS, maternal and child health, substance abuse, health manpower development, long-term care for the elderly, biomedical research, and national health insurance are presented. In addition, the importance of improving the general level of education and employment is stressed, as they have an impact upon health status. PMID- 3334062 TI - Metabolism and nervous system disease: a challenge for our times. Part I. PMID- 3334063 TI - Beta-hydroxybutyrate reverses insulin-induced hypoglycemic coma in suckling weanling mice despite low blood and brain glucose levels. AB - In normal suckling-weanling mice, DL-beta-hydroxybutyrate (30 mmol/kg ip) stimulated insulin secretion and reduced plasma glucose levels. In the brains of these animals, glucose levels were tripled due to a reduced rate of glucose utilization (determined by deoxyglucose phosphorylation). Other metabolite changes were compatible with inhibition of hexokinase, phosphofructokinase, glyceraldehyde-P-dehydrogenase, and pyruvate dehydrogenase activities. In contrast to the decrease in cerebral glycolysis, metabolite changes were compatible with an increase in the Krebs citric acid metabolic flux. The brain energy charge was also elevated. While it is generally believed that ketone bodies cannot sustain normal brain metabolism and function in the absence of glucose, DL-beta-hydroxybutyrate (20 or 30 mmol/kg ip) reversed insulin (100 U/kg sc)-induced hypoglycemia despite the persistence of a critically reduced plasma glucose concentration and near-zero brain glucose levels. Metabolic correlates of possible significance in the behavioral recovery from coma were reductions of the elevated levels of brain aspartate to below normal and ammonia levels to normal. Levels of acetyl CoA were unchanged both before and after treatment with beta hydroxybutyrate. PMID- 3334064 TI - Metabolism and nervous system disease: a challenge for our times. Part II. PMID- 3334067 TI - Desmoplastic fibroma of bone. PMID- 3334065 TI - Cerebral thiamine-dependent enzyme changes in experimental Wernicke's encephalopathy. PMID- 3334068 TI - Congenital radio-ulnar synostosis. Results of eight cases and review. PMID- 3334069 TI - Tularemia. A review. PMID- 3334066 TI - Selective vulnerability of brain: new insights from the excitatory synapse. PMID- 3334070 TI - Leptospirosis. A 10-year experience. PMID- 3334071 TI - Indications for breast preservation in stage I and stage II cancer of the breast. PMID- 3334072 TI - Heatstroke. A review of clinical manifestations and management. PMID- 3334073 TI - New PRO scope of work signals emphasis on quality. PMID- 3334074 TI - Invasive pulmonary aspergillosis. Report of a case. PMID- 3334075 TI - The cell in health and disease. An evaluation of cellular morphologic expression of biologic behavior. 2nd, revised edition. PMID- 3334076 TI - [Autobiographical note by Augusto Corradetti]. PMID- 3334077 TI - [Publications by Augusto Corradetti]. PMID- 3334078 TI - In the Roman Campagna from G. M. Lancisi to G. B. Grassi: two centuries of ideas, hypotheses and misunderstandings about malaria fevers. PMID- 3334079 TI - Correspondence with Corradetti. PMID- 3334080 TI - Thoughts on malaria in pregnancy with consideration of some factors which influence remedial strategies. AB - There is evidence that pregnancy enhances the clinical severity of malaria, especially of P. falciparum infections. In pregnant women with little or no prior experience of the disease, P. falciparum causes severe clinical illness, substantial malaria mortality, increased rates of abortion and stillbirth and low birthweight of offspring; moreover, in such women, the clinical consequences seen unmodified by maternal parity. However, in pregnant women resident in highly endemic areas who have acquired considerable immunity through prolonged prior contact with malaria, parity appears to influence susceptibility to an important degree. Women who are pregnant for the first time are most affected, showing increased prevalence and density of parasitaemia, increased frequency of clinical illness (but not mortality) and significantly increased frequency of delivery of low birthweight children. In contrast, in multigravid women these clinical features are much less obvious and rarely attain statistical significance. The differences in susceptibility to malaria of pregnant women associated with parity and previous immunological experience require that protective strategies must be planned with full knowledge of the local epidemiology of malaria and be specifically targeted to the women who require them. Furthermore, the effectiveness of each strategy requires careful monitoring to permit such modifications as may be required by change in the immune status of the resident population. PMID- 3334081 TI - Note on the history of cutaneous leishmaniasis in the Mediterranean and Middle East area. AB - There exist records of what seems to be cutaneous leishmaniasis at least as far back as 650 BC, and possibly much earlier in the Tigris/Euphrates basin. It was described by Avicenna in the 10th century AD, and was well-known in Aleppo and Baghdad by the 18th century AD. Cutaneous leishmaniasis due to Leishmania infantum may have occurred in Crete in the 18th century. Artificial transmission was effected in Algeria and Aleppo in the 18th century. PMID- 3334082 TI - Changes in the geographical distribution of malaria throughout history. AB - Climatic changes must have greatly affected the distribution of malaria in prehistoric times. Paleobotanical evidence, snowline depression studies and information obtained from deep sea sediment cores, indicate that southern Europe must have suffered a drop of summer temperatures of approximately 9 degrees C during the last glacial maximum, 18,000 years ago. Such a drop would have been decisive as regards the distribution of malaria and its vectors. If present at all, the disease would have been confined to the southernmost parts of the continent but P. falciparum and today's most effective vectors--A. labranchiae and A. sacharovi--would have been excluded from Europe. In western Asia, summer temperatures 6 degrees C lower than those of today would have had less effect on the malaria situation. The introduction of falciparum malaria in southern Europe is placed in Hellenistic and Early Imperial Roman times, based on paleoclimatological evidence and historical and medical data. In America P. falciparum is also considered a late entrant but vivax and quartan malaria may have been introduced in pre-Columbian times. In the Pacific, the disease is known to have been spread by man since the Age of Discovery until contemporary times. PMID- 3334083 TI - Ledger's cinchona seeds: a composite of field experience, chance, and intuition. AB - Following a short historical review of the facts which lead to the discovery of the specific action of the cinchona bark, an analysis is made of the obstacles encountered for more than two centuries by scientific expeditions to the identification, among the maze of natural hybrids, of the varieties of cinchona producing large amounts of quinine, and to obtain the best seed to establish plantations in other continents. Charles Ledger, a British general tradesman, was able to achieve that thanks to his alert spirit of observation, his (and that of his Bolivian servant Manuel) long experience of the Andes, and the chance that brought them to fall upon a group of exceptional cinchonas which had grown on an impervious slope of the Andes. Eventually the seeds were collected and Ledger offered them to the British and Dutch governments. Whereas the British failed to recognise their importance, the Dutch did not. They created extensive plantations in Java from which the world's demand for quinine was met, and the Dutch detained the practical monopoly of its production. PMID- 3334084 TI - The Dutch school of malaria research. AB - An epidemic of tertian malaria in some coastal areas of The Netherlands resulted in the setting up of official measures in 1920. A scientific and a propaganda commission were charged with control. Efforts were made to reduce mosquito populations by adult and larval spraying. After the discovery that infected mosquitoes were to be found only inside houses, control operations were focussed against adult mosquitoes. Some later discoveries resulted in a more effective control. a) Spraying ditches with Paris green did not prevent adult mosquitoes from entering the control area. b) Anopheles maculipennis turned out to be a complex of species, with A. atroparvus as the vector. The latter preferred brackish water and did not go into full hibernation. The closing of the Zuyder Sea and the expected desalinization gave hope for less suitable conditions for the vector. c) Plasmodium vivax normally had an incubation period of 8 months. d) Pyrethrum was an effective but short-lasting insecticide. e) Healthy parasite carriers could infect mosquitoes. This knowledge was applied through an extensive system of investigation, including spleen examination of schoolchildren. Suspected houses were sprayed bimonthly from August to November, during which period infected mosquitoes were likely to be present. This system worked extremely well, and during the next epidemic from 1943 to 1947 the thus treated towns remained virtually free of malaria! DDT became available and was either sprayed in suspected houses as before, or through wide-spread coverage of all houses. The epidemic subsided whatever method employed and not only due to the use of DDT. The number of cases even went down to the point of no return and the last case of Dutch malaria was recorded in 1959. The wealth of experience on house-spray control, parasite and mosquito biology and experimental malaria of the Dutch malariologists has had its impact on the international bodies engaged in the battle against malaria. PMID- 3334085 TI - [Augusto Corradetti]. PMID- 3334086 TI - Neuromelanin and its possible protective and destructive properties. AB - The function of neuromelanin is not known, but some properties of the pigment suggest a protective action. Its unique ability to accumulate and retain several compounds, such as various amines and a number of metals, may protect the pigment containing neurons from high exposure to harmful substances. This possible mechanism of protection may however in certain instances be of a double-edged nature, as accumulation of neurotoxic agents with a high melanin affinity may cause toxic concentrations in the neuro-melanin-containing cells. MPTP (1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine) seems to be such a compound, as it has been found to preferentially destroy neuromelanin-containing cells. The degree of MPTP neurotoxicity seems to be related to the amount of neuromelanin present in the particular species. It is possible that also manganese, which is known to cause an extrapyramidal disorder resembling Parkinson's disease, causes injury to neuromelanin-bearing neurons due to its melanin affinity. This mechanism may be involved in other forms of chemically induced Parkinsonism and possibly also in idiopathic Parkinson's disease, although the offending agent remains to be discovered. PMID- 3334087 TI - Determination of three-dimensional structures of proteins in solution by nuclear magnetic resonance spectroscopy. PMID- 3334088 TI - Automated protein crystallization and a new crystal form of a subtilisin:eglin complex. AB - A procedure is described for automating labour-intensive steps of the 'hanging drop' protein crystallization method. An automatic sample changer is employed to fill the wells in a multi-well plate so that concentration gradients in various components are obtained. The sample changer is also used for preparing droplets on a second multi-well plate. Subsequently, this second plate is manually turned around and placed on top of the first multi-well plate such that a large number of chambers with different conditions is obtained simultaneously. During initial trials a new crystal form of a subtilisin:eglin complex was obtained. The crystals have space group P2(1), contain two enzyme inhibitor complexes per asymmetric unit and diffract beyond 2.2 A. PMID- 3334089 TI - Improvement in the alkaline stability of subtilisin using an efficient random mutagenesis and screening procedure. AB - An efficient random mutagenesis procedure coupled to a replica plate screen facilitated the isolation of mutant subtilisins from Bacillus amyloliquefaciens that had altered autolytic stability under alkaline conditions. Out of about 4000 clones screened, approximately 70 produced subtilisins with reduced stability (negatives). Two clones produced a more stable subtilisin (positives) and were identified as having a single mutation, either Ile107Val or Lys213Arg (the wild type amino acid is followed by the codon position and the mutant amino acid). One of the negative mutants, Met50Val, was at a site where other homologous subtilisins contained a Phe. When the Met50Phe mutation was introduced into the B. amyloliquefaciens gene, the mutant subtilisin was more alkaline stable. The double mutant (Ile107Val/Lys213Arg) was more stable than the isolated single mutant parents. The triple mutant (Met50Phe/Ile107Val/Lys213Arg) was even more stable than Ile107Val/Lys213Arg (up to two times the autolytic half-time of wild type at pH 12). These studies demonstrate the feasibility for improving the alkaline stability of proteins by random mutagenesis and identifying potential sites where substitutions from homologous proteins can improve alkaline stability. PMID- 3334091 TI - Point mutation of alanine (31) to valine prohibits the folding of reduced lysozyme by sulfhydryl-disulfide interchange. AB - In the preceding paper in this issue, we described the overproduction of one mutant chicken lysozyme in Escherichia coli. Since this lysozyme contained two amino acid substitutions (Ala31----Val and Asn106----Ser) in addition to an extra methionine residue at the NH2-terminus, the substituted amino acid residues were converted back to the original ones by means of oligonucleotide-directed site specific mutagenesis and in vitro recombination. Thus, four kinds of chicken lysozyme [Met-1Val31Ser106-, Met-1Ser106-, Met-1Val31- and Met-1 (wild type)] were expressed in E. coli. From the results of folding experiments of the reduced lysozymes by sulfhydryl-disulfide interchange at pH 8.0 and 38 degrees C, followed by the specific activity measurements of the folded enzymes, the following conclusions can be drawn: (i) an extra methionine residue at the NH2 terminus reduces the folding rate but does not affect the lysozyme activity of the folded enzyme; (ii) the substitution of Asn106 by Ser decreases the activity to 58% of that of intact native lysozyme without changing the folding rate; and (iii) the substitution of Ala31 Val prohibits the correct folding of lysozyme. Since the wild type enzyme (Met-1-lysozyme) was activated in vitro without loss of specific activity, the systems described in this study (mutagenesis, overproduction, purification and folding of inactive mutant lysozymes) may be useful in the study of folding pathways, expression of biological activity and stability of lysozyme. PMID- 3334090 TI - Construction of a plasmid vector for the regulatable high level expression of eukaryotic genes in Escherichia coli: an application to overproduction of chicken lysozyme. AB - A novel expression vector pKP1500 for synthesizing unfused protein in Escherichia coli was constructed. pKP1500 perserves the tac promoter, the lacZ SD sequence, unique restriction sites (EcoRI, SmaI, BamHI, SalI, PstI and HindIII) and the rrnB terminators of pKK223-3, but the replication origin is replaced with that of pUC9. Construction of this plasmid is based upon the observation that the copy number control of pUC9 is temperature dependent. At 28 degrees C, the copy number of pKP1500 is less than 25 per chromosome, approximately the same copy number as that of pKK223-3, which contains the replication origin of pBR322, whereas at 42 degrees C, the copy number increases about 10 times and reaches up to 230 copies per chromosome. The main advantage of this system is that the temperature dependent copy control and regulatable expression of the tac promoter make cells carrying pKP1500 derivatives stable against selective pressure by detrimental overproduction of foreign proteins at a low temperature and permits high expression of cloned DNAs at a high temperature. When chicken lysozyme cDNA carrying the initiation codon (ATG) immediately upstream from the Lys1 codon was inserted downstream from the tac promoter and the SD sequence, the pKP1500 derivative produced lysozyme at about 25% of the total cellular proteins. This value is more than 10 times higher than that obtained with the pKK223-3 derivative carrying the same lysozyme cDNA. By comparison, the expression of eukaryotic genes from the tac promoter reported by others has usually been less than a few % of the total cellular protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3334093 TI - Expression of synthetic genes coding for completely new, nutritionally rich, artificial proteins. AB - Synthetic genes (A, AB and AHB) constructed and cloned into pKK233-2 vector were recloned from the parent plasmid into the new procaryotic expression vectors pGFY221N and pBI052. Gene AF-B (coding for all amino acids besides phenylalanine) was obtained by 'cassette mutagenesis' from gene AB. The plasmid pGFY221N was constructed from pGFY218L by replacing the PstI by an NcoI site; plasmid pBI052 was derived from pGFY221N through replacing the 221-bp EcoRI/NcoI fragment with a synthetic DNA segment of 52 bp representing the Escherichia coli atpE gene translational initiation region. The genes A, AB, AHB and AF-B in the vector pGFY221N were expressed with a six-amino-acid-long leader sequence; in pBI052 the genes were expressed directly. In vitro expression experiments were successfully with all the genes except with the AHB gene integrated into pGFY221N. In the E. coli minicell system expression was demonstrated with the A gene in pGFY221N and the AF-B and AHB genes in pBI052. Complete translation of the expressed genes AB, AF-B and AHB in either the in vitro or in vivo systems could be shown by using 35S-labelled N-terminal methionine and C-terminal cysteine. Both amino acids occur only once in the peptide sequences. PMID- 3334092 TI - Expression of the synthetic gene of an artificial DDT-binding polypeptide in Escherichia coli. AB - This paper reports the expression of an artificial functional polypeptide in bacteria. The gene of a designed 24-residue DDT-binding polypeptide (DBP) was inserted between the BamHI and PstI cleavage sites of plasmid pUR291. The hybrid plasmid, pUR291-DBP, was cloned in Escherichia coli JM109. After induction by isopropyl-beta-D-thiogalactopyranoside a fusion protein was expressed in which DBP was linked to the COOH-terminus of beta-galactosidase. DBP, which is stable to trypsin, was obtained by tryptic digestion of the fusion protein and subsequent fractionation of the tryptic peptides by reversed-phase h.p.l.c. Recombinant and chemically synthesized DBP showed identical chromatographic properties, amino acid composition, and chymotryptic digestion patterns. Both the beta-galactosidase-DBP fusion and isolated recombinant DBP bound DDT. The fusion protein was 25 times as potent as the designed 24-residue DBP in activating a cytochrome P-450 model system using equimolar catalytic amounts of the two proteins. PMID- 3334094 TI - The development of multiple expression vectors for high level synthesis of eukaryotic proteins: expression of LCMV-N and AcNPV polyhedrin protein by a recombinant baculovirus. AB - A copy of the polyhedrin gene promoter of Autographa californica nuclear polyhedrosis virus (AcNPV), in association with the coding region of lymphocytic choriomeningitis virus N protein (LCMV-N) and the relevant polyhedrin transcription termination signals, has been cloned into the unique EcoRV site of a plasmid representing an EcoRI derived fragment of the AcNPV genome. The cloning site is upstream (but in the opposite orientation) of the natural AcNPV polyhedrin gene. The derived pAcVC2 transfer vector has, therefore, both the normal polyhedrin gene and the LCMV-N gene each with its own copy of the polyhedrin transcriptional machinery. Co-transfection of Spodoptera frugiperda insect cells with the pAcVC2 plasmid together with infectious polyhedrin-negative AcNPV DNA resulted in the isolation of recombinant viruses that made polyhedrin protein as well as LCMV-N protein. Electron microscopy demonstrated the presence of occluded virus particles in the nucleus of the recombinant virus infected cells and aggregates of LCMV-N protein in the cytoplasm of the same cells. Unlike polyhedra-negative AcNPV recombinants, the occluded recombinants were potent infectious agents for the caterpillar Trichoplusia ni. The implications of these data are discussed in relation to the design of multiple eukaryotic expression vectors and recombinant baculovirus insecticides. PMID- 3334095 TI - Enzymatic semisynthesis of insulin specifically labelled with tritium at position B-30. AB - We have synthesized porcine insulin labelled with tritium at position B-30 using enzyme-catalysed formation of a peptide bond. The resulting insulin derivative has the label in the expected position and is biologically active. We have tested our procedure to prepare batches up to 50 muCi of tritiated insulin at a specific radioactivity of up to 1.14 Ci/mmol. PMID- 3334096 TI - Expression and characterization of Lactobacillus 30a histidine decarboxylase in Escherichia coli. AB - The genes coding for histidine decarboxylase from a wild-type strain and an autoactivation mutant strain of Lactobacillus 30a have been cloned and expressed in Escherichia coli. The mutant protein, G58D, has a single Asp for Gly substitution at position 58. The cloned genes were placed under control of the beta-galactosidase promoter and the products are natural length, not fusion proteins. The enzyme kinetics of the proteins isolated from E. coli are comparable to those isolated from Lactobacillus 30a. At pH 4.8 the Km of wild type enzyme is 0.4 mM and the kcat = 2800 min-1; the corresponding values for G58D are 0.5 mM and 2750 min-1. The wild-type and G58D have autoactivation half times of 21 and 9 h respectively under pseudophysiological conditions of 150 mM K+ and pH 7.0. At pH 7.6 and 0.8 M K+ the half-times are 4.9 and 2.9 h. The relatively slow rate of autoactivation for purified protein and the differences in cellular and non-cellular activation rates, coupled with the fact that wild type protein is readily activated in wild-type Lactobacillus 30a but poorly activated in E. coli, suggest that wild-type Lactobacillus 30a contains a factor, possibly an enzyme, that enhances the activation rate. PMID- 3334098 TI - Second-generation plasminogen activators. PMID- 3334097 TI - Cloning and expression in E. coli of a synthetic gene for the bacteriocidal protein caltrin/seminalplasmin. AB - A synthetic gene coding for the bacteriocidal protein caltrin/seminalplasmin was constructed and expressed in Escherichia coli as a fusion with beta galactosidase. The gene was designed with a recognition site for the plasma protease, Factor Xa, coded for immediately prior to the N-terminus of caltrin. The beta-galactosidase-caltrin fusion protein was cleaved with Factor Xa to give caltrin, which was identified by its size on SDS-PAGE, its ability to react with an antiserum raised to the N-terminal nonapeptide of caltrin and its N-terminal amino acid sequence. After partial purification, synthetic caltrin was found to be active in an assay involving inhibition of growth of E.coli. PMID- 3334100 TI - Efficient cleavage by alpha-thrombin of a recombinant fused protein which contains insulin-like growth factor I. AB - The gene for insulin-like growth factor I (IGF-I) was constructed from chemically synthesized deoxyoligonucleotides and expressed in Escherichia coli, under the control of a trp promoter, as a set of fusion proteins which were connected with a portion of human growth hormone through the recognition sequence for a sequence specific protease, either blood coagulation factor Xa or alpha-thrombin. Upon induction with 3-indoleacrylic acid, fusion proteins accumulated with a yield of 10-30% of the total protein. A fusion protein connected through a tetradecapeptide (Asp-Asp-Pro-Pro-Thr-Val-Glu-Leu-Gln-Gly-Leu-Val-Pro-Arg) was efficiently and correctly cleaved by alpha-thrombin, and the purified IGF-I possessed somatomedin-like activity, as determined by the enhancement of sulfation of glycosaminoglycans in cultured costal chondrocytes from rabbits. PMID- 3334102 TI - [Presence of auto-antibodies in patients who are candidates for heart transplant]. AB - A preliminary research, in order to evaluate by immunofluorescent technique the prevalence of heart specific and non specific autoantibodies, has been performed on a population of 58 cardiac patients, allograft applying. Two other populations (cardiac patients not allograft candidates, and healthy blood donors), were also tested as controls. Significant differences in the presence of specific anti heart antibodies were revealed among the three populations (89.7, 39.1 and 10%, respectively). No relevant correlation has appeared with the antibody titer between the two groups of cardiac patients. PMID- 3334099 TI - Hierarchical strategy for protein folding and design: synthesis and expression of T4 lysozyme gene and two putative folding mutants. AB - A T4 lysozyme-coding DNA sequence of 495 bp was chemically synthesized and cloned by ligation of 26 deoxyribooligonucleotide fragments in two steps with a linearized plasmid followed by transformation. On selection by colony hybridization and DNA sequence analysis, clone pTLY.10 was identified to contain a complete T4 lysozyme synthetic DNA. On expression under lac-promoter, unfused T4 lysozyme was obtained in approximately 4-6% yield. The design and synthesis of two putative folding mutants, flexible (Gly-Gly-Gly) and rigid (Asn-Asp-Gly) at position 73-74-75, were based on hierarchical principles. Both mutants lost enzymatic activity of the wildtype. These results are readily understandable if the hierarchical organization of the structure is taken into account. A possible explanation is that the catalytic sites are blocked in both mutants. PMID- 3334101 TI - Diphtheria toxin receptor binding domain substitution with interleukin-2: genetic construction and properties of a diphtheria toxin-related interleukin-2 fusion protein. AB - We have genetically replaced the diphtheria toxin receptor binding domain with a synthetic gene encoding interleukin-2 (IL-2) and a translational stop signal. The diphtheria toxin-related T-cell growth factor fusion gene encodes a 70 586-d polypeptide, pro-IL-2-toxin. The mature form of IL-2-toxin has a deduced mol. wt of 68,086 and is shown to be exported to the periplasmic compartment of Escherichia coli (pABI508), and contain immunologic determinants intrinsic to both its diphtheria toxin and IL-2 components. IL-2-toxin has been purified from periplasmic extracts of recombinant strains of E. coli (pABI508) by immunoaffinity chromatography using immobilized anti-IL-2. The purified chimeric toxin is shown to selectively inhibit protein synthesis in IL-2 receptor bearing targeted cells, whereas cell lines which do not express the IL-2 receptor are resistant to IL-2-toxin action. PMID- 3334103 TI - [Effect of aging on the renin-aldosterone system in healthy men]. AB - The relation between aging and plasmatic renin activity (PRA) and plasmatic aldosterone (PA) was studied in three groups of healthy normotensive male subjects: group A (subjects aged 20-40 years), group B (subjects aged 41-60 years), group C (subjects aged 61-80 years). Each group consisted of 15 subjects. All studied subjects were kept for a week on standardize life conditions with a defined daily intake of 120 mEq of sodium and 60 mEq of potassium. Venous blood samples were collected at 8.00 a.m., the subjects resting in supine position at least eight hours before the study. PRA and PA levels were determined by radioimmunoassay. The mean value of PRA and PA in the three groups were compared by t Student test. The results show that both PRA and PA present a decrease with age advancing: in fact the levels of PRA and PA are significantly higher in group A versus group B and group C, and in group B versus group C. The decline in PRA levels in the older subjects appeared to be due to various factors. It is concluded that aging process causes a decrease in PRA, with parallel lowering of PA and that these modifications have to be considered in biochemical diagnostic work-up of patients with arterial hypertension. PMID- 3334104 TI - [Central neurologic damage and local ischemic compromise secondary to injection of benzathine penicillin]. PMID- 3334105 TI - Retrospective evaluation of the immunoreactivity of viral antigens after several years of "formalin" fixation at ambient temperature: a rabies virus immunoperoxidase model. PMID- 3334106 TI - Clinical aspects of renal prostaglandins and NSAID therapy. AB - Nonsteroidal antiinflammatory drugs (NSAIDs) can have a variety of effects on renal function. Excluding allergic phenomena, these are directly related to NSAID induced inhibition of renal synthesis of prostaglandins (PGs). For the most part, renal PGs play important physiological roles only in certain pathologic conditions. Thus, patients without these diseases (such as cardiac, hepatic, or renal compromise) manifest no or only trivial effects on renal function when NSAIDs are administered. This feature is to the advantage of the clinician because it allows prospective identification of patients who are at risk for an adverse renal effect; hence, such effects can be minimized or avoided altogether. To do so requires an understanding of the various roles of PGs in the kidney and thereby the effects that one can observe from NSAIDs. This review focuses on these various roles of renal PGs and on identification of patient groups at risk for adverse renal effects of NSAIDs. PMID- 3334107 TI - A multicenter study of the safety and efficacy of naproxen: analysis of blood pressure. AB - A multicenter study was conducted to determine safety and efficacy of naproxen, 500 mg twice daily, administered for 4 weeks to osteoarthritis (OA) patients. OA symptoms improved in the study population. The study population included 97 patients, 43 of whom were 65 years of age or older. Forty-four of the 97 patients had a history of hypertension; 42 of these took antihypertensive medication before and during the study. Baseline blood pressure (BP) was measured in most patients while they were receiving their prior nonsteroidal antiinflammatory drug (NSAID) therapy; from that baseline, no increase in BP was seen in the hypertensive or normotensive patients after 4 weeks of naproxen therapy. In patients whose BP was controlled by antihypertensive agents, BP remained under control during naproxen therapy. PMID- 3334108 TI - Hepatic and renal tolerability of long-term naproxen treatment in patients with rheumatoid arthritis. AB - Clinical and laboratory assessments of hepatic and renal function in rheumatoid arthritis (RA) patients who received naproxen for up to 6 months during two randomized, double-blind studies comparing naproxen 375 mg twice daily (n = 286) with naproxen 750 mg twice daily (n = 300) were analyzed. Patient groups were segregated by dosage, duration of treatment, and age at entry (less than 65 years v greater than or equal to 65 years), and laboratory measurements of SGOT, SGPT, serum creatinine (Scr), and BUN were examined. Records of individual patients with clinically meaningful abnormalities in laboratory tests or adverse events of hepatic or renal origin were examined in detail. Over the duration of these studies, there were no clinically meaningful changes in mean laboratory values or differences in occurrences of abnormal values among the different patient groups. In both dosage groups, pretreatment incidences of clinically meaningful abnormalities in laboratory tests were similar to those in serial observations during treatment. Six patients who received naproxen 375 mg twice daily and four patients who received naproxen 750 mg twice daily had a hepatic or renal clinical event or distinctly abnormal laboratory value, but only three of these withdrew because of these problems. Occasional transient abnormalities of conventional laboratory tests of hepatic and renal function occurred in some patients during naproxen treatment. Such abnormalities called for careful patient monitoring but generally did not warrant immediate drug withdrawal. PMID- 3334109 TI - The use of a 51Cr technique to detect gastrointestinal microbleeding associated with nonsteroidal antiinflammatory drugs. AB - Of techniques used to evaluate gastrointestinal (GI) bleeding, use of radiochromium (51Cr)-tagged erythrocytes is the most quantitative and scientifically acceptable method. The value of this technique as well as systematic errors possible with its use are discussed. The medical literature concerning 51Cr evaluation of GI microbleeding with naproxen therapy is critically reviewed. We suggest that future studies using this technique be parallel, randomized, double-blind, and include a 1-week placebo baseline phase for all subjects. Treatment with nonsteroidal antiinflammatory drugs (NSAIDs) should last 3 to 4 weeks. A parallel group of subjects should receive placebo throughout the study. For valid statistical analyses, randomization must achieve baseline comparability of weight, height, age, and sex in the treatment groups. Data transformations may be necessary to satisfy the assumptions of the statistical model. Following these guidelines will enable investigators to better evaluate GI microbleeding during treatment with naproxen or other NSAIDs, and, hopefully, to establish the safety profiles of these drugs. PMID- 3334110 TI - Development of behavioral states in hydrocephalic fetuses. AB - Behavioral states observations were carried out in 12 hydrocephalic fetuses by means of a computerized system. Recordings of behavioral parameters, including fetal heart rate, gross body movements, breathing movements and eye movements, were performed at 2-week intervals from 30 weeks of gestation onwards. The hydrocephalic fetuses showed quantitative and qualitative differences in their motor behavior in comparison to healthy fetuses of equivalent gestational age. Similarly the appearance of behavioral states was delayed in hydrocephalic fetuses. Furthermore, an increased discordance between the behavioral parameters was evidenced. The degree of discordance seems to be related to the severity of neonatal outcome suggesting a possible estimation of CNS dysfunction by means of behavioral state analysis. PMID- 3334111 TI - Fetal urinary electrolytes in bladder outlet obstruction. AB - Ultrasound findings and urinary electrolytes in the fetus were correlated with fetal outcome and postmortem findings in 8 cases of fetal bladder outlet obstructions. One of the two fetuses, suggesting normal renal function according to urinary electrolytes, displayed renal dysplasia at birth. Six fetuses were predicted to have poor renal function, 5 of these were found to have renal dysplasia at autopsy. The interpretation of fetal urinary electrolytes as a prognostic indication for the presence or absence of renal dysplasia needs to be clarified. PMID- 3334112 TI - An open study with ticlopidine in cerebral reversible ischemia. PMID- 3334113 TI - Orthostatic hypotension. Mechanisms and hemodynamics. PMID- 3334114 TI - [Therapy of pulmonary bacterial infections with amoxicillin and clavulanic acid: clinical experience]. PMID- 3334115 TI - [Therapy of infective respiratory diseases with a shielded beta-lactam antibiotic (amoxicillin and clavulanic acid)]. PMID- 3334117 TI - [Therapy of acute or recurring chronic respiratory infections with mezlocillin]. PMID- 3334116 TI - [Clavulanic acid-shielded amoxicillin in the treatment of acute and chronic infective diseases of the pulmonary system]. PMID- 3334118 TI - "Hypoglycemic" anxiety. The role of reinforcement in psychophysiological disorders. PMID- 3334119 TI - Dating-skills groups for the developmentally disabled. Social skills and problem solving versus relaxation training. PMID- 3334120 TI - Limitations of operant practice in the study of disease. PMID- 3334121 TI - The relevance of metabolic rate in behavioral medicine research. PMID- 3334122 TI - Assessment and treatment of cognitive deficits in brain-damaged individuals. PMID- 3334123 TI - Exercise in cardiovascular disease. PMID- 3334124 TI - Psychological assessment and treatment of irritable bowel syndrome. PMID- 3334125 TI - Innovative treatment approaches to bulimia nervosa. PMID- 3334126 TI - Cognitive-behavioral treatment of bulimia nervosa. A critical appraisal. PMID- 3334127 TI - The present status of operant conditioning for the treatment of anorexia nervosa. PMID- 3334128 TI - A review of behavioral treatments for bulimia nervosa. PMID- 3334129 TI - Body image in anorexia nervosa and bulimia nervosa. A review of the literature. PMID- 3334130 TI - Contrast and comparison of behavioral, cognitive-behavioral, and comprehensive treatment methods for anorexia nervosa and bulimia nervosa. PMID- 3334131 TI - Effect of splenectomy on allograft survival and leukocyte migration in rat cardiac transplantation. PMID- 3334132 TI - The Harderian gland and the porphyrins. PMID- 3334134 TI - The general development of Chinese ophthalmology. PMID- 3334133 TI - The phylogeny of the endocrine system. PMID- 3334135 TI - [The epidemiological survey of blindness and low vision in Sichuan Province, China]. PMID- 3334136 TI - Biological significance of secondary lipid oxidation products. PMID- 3334137 TI - Biological implications of microtubule dynamics. PMID- 3334138 TI - Virus structure, function, and evolution. PMID- 3334139 TI - Lessons from the life cycle of retroviruses. PMID- 3334140 TI - "Forward" and "reverse" genetics of inherited human disorders: the thalassemia syndromes and chronic granulomatous disease. PMID- 3334141 TI - Molecular biology of active transport: from membrane to molecule to mechanism. PMID- 3334142 TI - Arthropod parasites of some wild animals in South Africa and Namibia. AB - Earlier research on the parasites of wild animals in South Africa is reviewed and the findings of more recent research discussed. The life cycles of various gasterophilid and oestrid fly species are described and the seasonal abundance of their larvae in their zebra and antelope hosts is considered. The seasonal abundance of fleas, lice and ixodid ticks on their hosts is given and the role played by both small and large mammals and some birds in the maintenance of tick populations is described. Factors contributing to severe parasitism of wild animals are listed and the chemical and biological control of ectoparasites of wild animals are discussed. PMID- 3334143 TI - The veterinarian as biologist. PMID- 3334144 TI - Poisoning of wildlife in southern Africa. AB - Wildlife can be poisoned by both plants and chemicals. The co-evolution of wildlife and toxic plants has resulted in an increased resistance to these substances as compared with domestic animals. Both groups of animals are however susceptible to chemical poisons. The results of experimental poisonings with Dichapetalum cymosum, Urginea sanguinea, Senecio retrorsus, Nicotiana glauca and prussic acid are discussed. The effect of poisoning of wildlife with Crotalaria spp. Geigeria spp, Lantana camara, chlorinated hydrocarbons, organophosphates, carbamates, strychnine, heavy metals and other plants and chemicals is reviewed. PMID- 3334145 TI - [The anterior enteritis syndrome in the horse]. AB - The anterior enteritis syndrome in the horse is reviewed with reference to the aetiology, pathogenesis, clinical findings, laboratory findings, diagnosis, treatment, prognosis and post mortem findings. PMID- 3334146 TI - Winner of the Boswell award for 1987. Dr. C. M. Veary. PMID- 3334148 TI - [Recipient of the research award of the SAVV for 1987. Dr. J. D. Bezuidenhout]. PMID- 3334147 TI - Clinical award of the South African Veterinary Association for 1987. Dr. O. M. Briggs. PMID- 3334149 TI - Silver Medal of the South African Veterinary Association posthumously awarded to the late John Murray (Ian) Hofmeyr. PMID- 3334150 TI - [Silver Medal of the SAVV. Dr. L. Coetzee]. PMID- 3334151 TI - [Gold Medal of the South African Veterinary Association for 1987. Dr. A. Polson]. PMID- 3334152 TI - Immunology of leprosy: new findings, future perspectives. PMID- 3334153 TI - Genetic mapping of novel virulence determinants of Salmonella typhimurium to the region between trpD and supD. AB - Salmonella typhimurium strains are known to vary greatly in their virulence for mice. A few of the genes affecting their virulence have been described. In this report we have localized at least two genes that affect the ability of S. typhimurium to grow in BALB/cByJ to a 6 unit section of the salmonella chromosome which does not contain any previously described virulence determinants. The genetic mapping was done by interrupted matings using Hfr strains made in a virulent LT2 strain. The Hfr strains were constructed by inserted the plasmid F'(TS)114 lac+ Tn::10 into the LT2 chromosome at specific sites through homologous recombination with chromosomal Tn10s. Short interrupted matings to an avirulent LT2 strain in either direction through the portion of the chromosome from trpD at 34 units to supD at 40 units resulted in transconjugants which were fully virulent. Since we also found several transconjugants with intermediate virulence it appears that more than one virulence gene may exist in this area of the chromosome. The mechanisms of action of these genes are not known. PMID- 3334155 TI - Fallacies of E. coli cell fractionations and consequences thereof for protein export models. PMID- 3334154 TI - Isolation of a C (Ibc) protein from group B Streptococcus which elicits mouse protective antibody. AB - The C (Ibc) proteins of group B Streptococcus (GBS) have been shown to induce mouse protective antibodies when present as immunogens on whole organisms. However, characterization of specific proteins responsible for inducing protection has not been reported. We have grown type Ic GBS in a dialysate of Todd Hewitt broth and analyzed the proteins extruded into the broth. Multiple proteins of varying size were visualized by SDS-PAGE. Ultrafiltration was used to separate the GBS components by molecular weight (MW) into 2 pools, those below 30,000 MW but above 10,000 MW (P10) and those above 30,000 MW (P30). The P10 contained 4 major proteins, including a 14,000 MW protein. Balb-c mice were immunized with the P10 fraction and the antisera used in mouse protection studies. This immune sera protected 100% of mice against challenge with type Ib GBS and protection was not altered by prior absorption of the sera with type Ia or Ib capsular polysaccharide. The P10 was fractionated by column chromatography and eluted proteins examined by SDS-PAGE and Western blot with the mouse protective antisera elicited to the P10. There was one major immunologically reactive protein at 14,000 MW which eluted in a partially purified form from the column. The 14,000 MW protein was reisolated from preparative SDS-PAGE gels and used to elicit antiserum in a rabbit. In mouse protection studies this rabbit antiserum protected mice against subsequent challenge with type Ib GBS (89% protection). Surface antigens were extracted from 125I-labelled type Ic GBS and immunoprecipitated with antiserum to the 14,000 MW protein. The 14,000 MW protein and multiple higher molecular weight proteins were immunologically cross-reactive suggesting the presence of shared epitopes. Thus the 14,000 MW protein from type Ic GBS that is antigenic and elicits mouse protective antibodies against the heterologous type Ib GBS fulfills the criteria for a C protein of GBS. PMID- 3334156 TI - Shiga toxin from Shigella dysenteriae 1 inhibits protein synthesis in reticulocyte lysates by inactivation of aminoacyl-tRNA binding. AB - Inhibition of the peptide elongation cycle of eukaryotic protein synthesis by Shiga toxin from Shigella dysenteriae 1 was examined in toxin-treated reticulocyte lysate mixtures. Peptidyl transferase activity of toxin-treated ribosomes was measured by following the decrease in peptidyl-tRNA concentrations when puromycin was added after incubation with toxin. Concentrations of [3H]leucine-labeled peptidyl-tRNA were measured by extraction with cetyltrimethylammonium bromide. The data suggest that Shiga toxin inhibited aminoacyl-tRNA binding. Toxin-treated ribosomes retained peptidyl transferase activity, and toxin did not block translocation. Furthermore, no inhibition of initiation of protein synthesis could be observed. Finally, Shiga toxin had no detectable nucleolytic effect on polysomal 28S rRNA, nor was hydrolysis of 5.8S or 5S rRNA observed. PMID- 3334157 TI - Genetics of virulence in Shigella. PMID- 3334158 TI - Cloning and expression in Escherichia coli and Staphylococcus aureus of the beta lysin determinant from Staphylococcus aureus: evidence that bacteriophage conversion of beta-lysin activity is caused by insertional inactivation of the beta-lysin determinant. AB - The beta-lysin determinant (Hlb) from Staphylococcus aureus CN6708 was cloned in Escherichia coli K-12 using the bacteriophage replacement vector lambda L47.1. The Hlb determinant was localised to a 1250 base pair DNA sequence by cloning fragments from a Hlb+ recombinant phage into the plasmid vectors pACYC184 and pBR322 in E. coli K-12, and by the subsequent construction and analysis of several sub-clones, in vitro deletion and Tn5 insertion mutations. E. coli cells harbouring Hlb+ plasmids expressed readily detectable levels of beta-lysin and sphingomyelinase activity, which were located in the cytoplasm. Two polypeptides of molecular weight 38,000 and 33,000 which were encoded by the Hlb determinant were detected in E. coli minicells, but only the 33,000 dalton protein was detected in immunoblotting experiments with specific anti-beta-lysin serum. Hybridisation analysis with probes made from the cloned Hlb determinant and from DNA of the staphylokinase-converting phage phi 13, indicated that bacteriophage conversion of S. aureus to loss of beta-lysin activity is due to insertion of phi 13 DNA into or adjacent to the beta-lysin determinant. A shuttle plasmid was used to transfer the cloned Hlb determinant into a beta-lysin negative strain of S. aureus where the wild-type chromosomal determinant was inactivated by lysogenic conversion. Beta-lysin activity was readily detected in supernatants of S. aureus harbouring the cloned determinant. PMID- 3334159 TI - [Dental caries: etiologic and preventive aspects]. PMID- 3334160 TI - [Importance of cavity varnishes in clinical restorative dentistry]. PMID- 3334161 TI - [Use of diazoxide in the studies of the effect of glucagon on the blood serum levels of glucose, free fatty acids and triglycerides in rabbits]. AB - Diazoxide was used to prevent the high insulin secretion after glucagon administration to rabbits. Using of this benzothiadiazine allowed to investigate an effect of glucagon on the blood glucose, free fatty acids and triglycerides without raised insulin. The concentration of serum glucose was increased in all experiments (with or without diazoxide infusion), however both normoinsulinemic and hyperinsulinemic rabbits showed return to the control value in the end of experiments. In the case of FFA the high level of insulin was necessary to return their concentration to the control value. Glucagon alone had no effect on serum TG level. PMID- 3334162 TI - Fast atom bombardment mass spectrometry and its application to the analysis of some peptides and proteins. AB - The techniques of fast atom bombardment mass spectrometry has overtaken (but not entirely replaced) field desorption mass spectrometry as the method of choice for the analysis of nonvolatile, thermally labile polar compounds. The ease with which information may be obtained on a wide variety of molecules is a result of the relative simplicity of the technique. A brief history of bioorganic mass spectrometry leading to the development of fast atom bombardment is presented, as well as a description of the method and ancillary techniques. Selected examples of its application to peptide and protein structural problems attest to the power and utility of fast atom bombardment mass spectrometry. PMID- 3334163 TI - The lipoidal permeability barriers of the skin and alimentary tract. AB - The major routes of administration of drugs to humans involve transport either through the intestinal wall or through the skin. Both these barriers are nonpolar in nature and are subserved by membrane lipids. The lipid composition of the brush border of the intestinal wall is unusual, possessing unusually large quantities of glycosylceramide. The lipid composition of the stratum corneum of the skin is also unusual, possessing large quantities of ceramides and free fatty acids. These atypical membrane components are generally more ordered than the other common membrane lipids at body temperature and, thus, are suited for involvement in formation of barriers between the organism and its environment. PMID- 3334164 TI - Protein degradation: the role of mixed-function oxidases. AB - The mechanisms by which protein oxidation is mediated in the cell are of both biological and pharmacological importance. Oxidases responsible for the metabolism of xenobiotics catalyze the oxidative inactivation of select enzymes. Oxidation mediated by mixed-function oxidase (MFO) systems renders proteins more susceptible to proteolysis and, consequently, appears to be a signal for protein degradation. The mode of action of MFO systems is discussed in detail for a specific, well-characterized system--the MFO-catalyzed oxidation of glutamine synthetase (GS). Findings for this system are then generalized to help explain how other metabolic enzymes are oxidized by MFO systems. The broader consequences of oxidative mechanisms are discussed. For example, the accumulation of modified proteins during aging and in some premature aging diseases may be due in part to shifts in the relative rates of oxidation and degradation for these proteins. Further, the oxidation of key metabolic enzymes appears to be responsible for the bacteriocidal action of neutrophils. There is also some evidence that the degradation of endogenous proteins increases following ingestion of, or exposure to, agents that induce MFO activity. PMID- 3334165 TI - Enantiomeric resolution of drug compounds by liquid chromatography. AB - Novel techniques have recently emerged to separate chiral drug compounds into pure enantiomers. The mechanism, experimental difficulties, and applicability of these methods can very greatly, and the choices involved are not straightforward. The most significant new advances in the field of chiral separations have come from work done with liquid chromatographic systems and chiral stationary-phase columns. This review describes several commonly used approaches to chiral separation, dia-stereomeric derivatization, chiral mobile-phase additives, and three major types of chiral stationary phases. Although no single method can be judged superior for every drug application, it appears that chiral stationary phases have received the most attention recently and they are emphasized here. PMID- 3334166 TI - Renin inhibitors. AB - Pharmacological intervention in the renin-angiotensin system (RAS) by inhibition of angiotensin-converting enzyme (ACE) is an effective therapy for the majority of hypertensive patients and a major advance in the treatment of hypertension and congestive heart failure. The success achieved with ACE inhibitors has increased interest in inhibitors of renin. Renin catalyzes the first and rate-limiting step of the RAS and, unlike ACE, has a high specificity for its endogenous protein substrate. A therapeutic agent that inhibits this specific reaction could have advantages over antihypertensive drugs with less specific modes of action. Although inhibitors of renin have been studied for over two decades, only recently has substantial progress been made toward potent, low molecular weight inhibitors likely to become useful therapeutic agents. Recent advances in the development of renin inhibitors, especially progress toward clinically useful inhibitors, is reviewed. PMID- 3334169 TI - Prevention of infection in colonic surgery by rifaximin. A controlled, prospective, randomized trial. PMID- 3334168 TI - Electron-transfer and charge-transfer clastic binding hypotheses for drug receptor interactions. AB - The origins and development of clastic binding hypotheses for interaction of morphines with the opiate receptor and various hallucinogens with their putative receptors are reviewed. Possible alternative explanations of the facts which led to the clastic binding hypotheses are offered. Possible integration of the clastic binding processes into other, better-recognized processes at the receptors is considered. PMID- 3334170 TI - Rare syndromes. II. Joubert syndrome: a review of the 43 cases published in the literature. PMID- 3334167 TI - The influence of drugs on nasal ciliary movement. AB - Drugs in nasal preparations, for local use as well as for systemic use, should not interfere with the self-cleaning capacity of the nose, effectuated by the ciliary epithelium. Many drugs and additives, however, have a negative effect on nasal ciliary function. Examples of ciliotoxic agents are lipophilic and mercuric preservatives, local anesthetics, antihistamines, propranolol, and absorption enhancers such as the bile salts. Cholinergic drugs and beta-adrenergic drugs exert a ciliostimulatory effect. It is the purpose of this review to summarize the present knowledge of ciliotoxicity of drugs and additives and to give recommendations for the use of ciliofriendly drugs in nasal preparations. PMID- 3334171 TI - Hydrocephalus and vasopressin: a reassessment. PMID- 3334173 TI - Rare syndromes. I. Cockayne syndrome: a review of the 129 cases so far reported in the literature. PMID- 3334172 TI - [What is the ideal sweetener?]. PMID- 3334174 TI - [Preliminary evaluation of the therapeutic efficacy of a combination of captopril 50 mg + hydrochlorothiazide 25 mg (Aceplus 50/25)]. PMID- 3334175 TI - [Modification of PRA, aldosterone, prolactin, and parathyroid hormone serum levels by "head-out" water immersion]. PMID- 3334177 TI - Diabetic hyperlipoproteinemia. PMID- 3334176 TI - [Captopril in hypertensive psychiatric patients]. PMID- 3334178 TI - [Lipids and peripheral arteriopathies]. PMID- 3334179 TI - [Clinical-instrumental diagnosis of tumors of the tongue and oral floor]. PMID- 3334180 TI - Arnaldo Cantani (Sr) then and now: clinician, scientist, and teacher (2). PMID- 3334181 TI - Inborn errors of metabolism associated with cataracts. PMID- 3334182 TI - [Histaminic provocation in allergy. The role of ascorbic acid]. PMID- 3334183 TI - [Treatment of hemorrhoids with the Barron method: a crystalline lattice preparation]. PMID- 3334185 TI - [Drug therapy of the allergic respiratory syndrome. Practical note]. PMID- 3334184 TI - [Effect of treatment with captopril on the quality of life in hypertensive patients. Multicenter study in ambulatory patients]. PMID- 3334186 TI - Perforated peptic ulcer in south-eastern Nigeria 1973-1982. AB - In a prospective study aimed at evaluating a safe treatment for tropical African conditions 205 patients who presented with perforation of a peptic ulcer in South Eastern Nigeria during the ten year period January 1973 to December 1982 were treated by simple suture. The ulcers were classified at operation from appearance as acute in 155 patients (75.6%), and chronic in the remaining 50 patients (24.4%). Of this number 21 patients (10.2%) died post-operatively. All 21 patients had chronic pyloroduodenal ulcers which were complicated by haemorrhage in 10 patients (5.0%) and extensive scarring of the duodenum and pyloric stenosis in 9 patients (4.4%). In contrast, no patient with acute pyloroduodenal ulcer died and none was known to suffer from recurrent dyspepsia at 6 months to 1 year follow-up. These results show that simple suture is an adequate and safe treatment for perforated acute pyloroduodenal ulcer but this treatment is, however, followed by an unacceptably high mortality in patients with perforated chronic pyloroduodenal ulcers in whom were feasible, a definitive ulcer--curative surgery should be performed. PMID- 3334187 TI - Prevention of recurrent ulcer bleeding, a multicentre study of the effect of ranitidine and trimipramine over one year. AB - Short term studies of the prevention of bleedings from peptic ulcers and erosions have been reported by a number of authors following treatment with antacids (1), H2-receptor blockers, cimetidine (2-15), a combination of cimetidine and tranexamic acid (16), cimetidine and somatostatin (17), cimetidine and sucralfate or secretion (18, 19, 20), cimetidine compared to antacid (21), and cimetidine compared to antacid and pirenzepine (22). The H2-blocker rantitidine has been compared to placebo (24, 25, 26). An uncontrolled study has been performed using proglumide (27), a controlled study with vasopressin (28) and with secretin versus somatostatin (28). In the studies with H2-receptor antagonists conflicting results have been obtained. No report has been published concerning the effect over more than a few days or weeks. PMID- 3334188 TI - Non-ulcer dyspepsia in Nigerians clinical and therapeutic results. AB - To determine the role of hyperacidity non-ulcer dyspepsia, forty-five Nigerians with this diagnosis were compared with twenty patients with proven duodenal ulcer with regard to their basal, maximal and peak acid outputs. The mean basal, maximal and peak acid outputs for the duodenal ulcer group were 6.72, 21.4 and 30.6 mol/h, respectively. In contrast, the corresponding values in non ulcer dyspepsia were 3.46, 13.03 and 17.83 mol/h respectively. This value in the two groups were significantly different. The efficacy of ranitidine at 300 mg daily for the control of the symptoms of non-ulcer dyspepsia was compared with placebo in a double-blind 4-weeks clinical trial. There was no significant difference in the response of the two groups comprising twenty-three and twenty-two patients, respectively. It is concluded that hyperacidity probably plays little role in non ulcer dyspepsia and that the newer anti-ulcer drugs may be of little benefit under these circumstances. PMID- 3334189 TI - Double immunofluorescence studies of IgA and poly C9 (MAC) in glomeruli from patients with IgA nephropathy. AB - Double immunofluorescent studies on IgA, poly (MAC) or C3 in glomeruli from patients with IgA nephropathy are described. Renal biopsy specimens were obtained from 12 patients with IgA nephropathy, four patients with proliferative glomerulonephritis (PGN) and two normal human kidney (NHK). These specimens were incubated with monoclonal anti-poly C9 (membrane attack complex; MAC) and then stained with FITC-labelled goat anti-mouse immunoglobulin (Ig) antiserum. After washing with phosphate buffered saline (PBS) (pH 7.4), the sections were stained with rhodamine-labelled rabbit anti-human IgA antiserum and examined by fluorescence microscopy. The sections were also stained with FITC-labelled goat anti-human C3 antiserum and then stained with rhodamine-labelled rabbit anti human IgA antiserum. Markedly combined depositions of IgA and poly C9 or C3 in glomeruli were observed in patients with IgA nephropathy. There was a significant correlation between the deposition of poly C9 and the grading of histopathological injuries in such patients. There was also a significant correlation between the deposition of poly C9 in the extraglomerular vascular vessels and the ageing in patients with IgA nephropathy, PGN and NHK. It appears that the deposition of poly C9 might detect directly the activities of complement in glomeruli from patients with IgA nephropathy. PMID- 3334190 TI - Detection of immunoglobulin depositions by immunofluorescence and/or immunoperoxidase (P-AP method) in patients with IgA nephropathy. AB - Deposition of immunoglobulins in the glomeruli by immunoperoxidase (IP) and/or immunofluorescence (IF) using unfixed materials obtained from 25 patients with IgA nephropathy (IgAN) was evaluated. The results indicated that the deposition of IgA, IgM or IgG in the glomerular capillary walls using a peroxidase anti peroxidase (P-AP) method was more prominently detected than by using IF. The results of double staining indicated that both P-AP and IF were able to stain mesangial and capillary depositions of IgA was more widely detected by P-AP than by IF. It is concluded that the P-AP method has the advantage of indicating the deposition of immunoglobulins in glomerular capillary walls, and evaluating the histopathological significance together with IF in patients with IgAN. PMID- 3334192 TI - [Administrators of the Main Hospital of Saint John the Baptist and City of Turin from the Valli di Lanzo]. PMID- 3334191 TI - Biochemical characterization and immunohistochemical localization of progestin and estrogen receptors in castrate rat submandibular gland. AB - The physicochemical property and immunohistochemical localization of progestin (P) and estrogen (E) receptors (PR and ER) were examined in the submandibular gland (SMG) of 5-8-week-old castrated rats. The localization of epidermal growth factor (EGF) was simultaneously examined in the same tissue. The tissue cytosols from male and female rats specifically bound 3H-promegestone (3H-R5020) and 3H estradiol-17 beta with high affinity and low capacity; the values were within the range of those reported for other tissues. However, E-treatment suppressed the specific P-binding in the female, whereas it did not in the male. On the contrary, E-treatment did not at all suppress specific E-binding in both sexes. Monoclonal antibodies against PR and ER were mainly located in the epithelium of the excretory duct and granular convoluted tubule, but not in the acinus. The monoclonal antibodies were also located in the large polygonal cell with irregular cell border, probably macrophage in the tissue. The EGF immunoreactivity was observed in the epithelium of the same tissue region as that in which the monoclonal antibodies were located. The present results clearly suggest that the rat SMG tissue contains specific PR and ER that are mainly located in the epithelium of the duct system where EGF-producing cells are also located. The possibility that P and E may influence EGF-production through their receptors in this tissue was discussed. PMID- 3334193 TI - [150th anniversary of the death of Carlo Botta. Medical doctor, politician, historian, scholar, musicologist]. PMID- 3334194 TI - [Substitutive therapy with surfactants in premature infants with respiratory distress syndrome]. AB - The main pathogenetic moment of the respiratory distress syndrome (RDS) is recognized to be the lack of alveolar surfactant. Many attempts of substitutive therapy with several kinds of surfactants have been tried (artificial, synthetic, from amniotic fluid, exosurf). After the considerable results obtained in animals, the use of substitutive surfactant proved to be useful also in human newborns with RDS. The authors report the personal data relative to the TA surfactant (artificial surfactant made of phospholipids + DPPC + protein substances extracted from bovine lung). They analyse first results and, on this ground, they put forward some assumptions in order to obtain a more rational and efficient use. PMID- 3334196 TI - [Third molars in relation to orthodontic treatment]. PMID- 3334197 TI - [Traumatic rupture of the diaphragm]. AB - A survey based on 122 personal observations of traumatic rupture of diaphragm, involving stomach and spleen herniation into the chest, is presented. The importance of clinical symptoms for proper diagnosis and treatment is discussed, in relation to the different trends in the literature. PMID- 3334198 TI - Lactic acidosis in childhood: Part II. AB - Lactic acidosis is associated with both inherited and acquired metabolic diseases. Lactic acid metabolism in the presence of altered gluconeogenesis, anaerobic glycolysis, and acid-base balance is a major factor in many disorders. Lactic acid can be formed only from pyruvic acid; therefore, disorders that increase pyruvate concentration, enhance lactic acid formation, or reduce lactic acid degradation cause lactic acidosis. Inborn metabolic errors that are accompanied by derangement of metabolic pathways of glucose, pyruvate, amino acids, and organic acids as well as toxic and systemic conditions that promote tissue hypoxia or mitochondrial injury result in lactic acidosis. In the presence of acquired disorders, treatment is directed initially toward modification or cure of the primary condition and then toward eliminating acidosis and other metabolic complications. Specific therapy is available for some inborn errors of metabolism. PMID- 3334195 TI - [Root resorption, decalcification and orthodontic treatment]. PMID- 3334199 TI - The migraine syndrome in children and adolescents. AB - Headache has a remarkably constant occurrence in different socioeconomic, cultural, geographic, and ethnic groups. Between 70% and 90% of people surveyed had at least one headache in the preceding year. Twenty-one percent of children have had significant tension or migraine headaches by 15 years of age, and an additional 54% have experienced occasional, less significant headache. Of children who had migraine, 42% lost time from school because of their headaches. Three percent of adults lost time from work because of headaches. This common symptom requires an organized approach to diagnosis and treatment. PMID- 3334200 TI - Brainstem gangliogliomas. AB - Gangliogliomas are rare neurogliogenic tumors of the central nervous system. Primary involvement of the brainstem is characterized by variable presentations and a long clinical course before diagnosis. Identification of this group of tumors is essential because clinical improvement and prolonged survival have been documented following partial surgical resection. PMID- 3334201 TI - Nocardia asteroides brain abscess following mastoidectomy. AB - Nocardia asteroides brain abscess occurred after mastoidectomy and tympanoplasty in a previously healthy 10-year-old boy. Combined surgical excision and trimethoprim/sulfamethoxazole therapy resulted in significant improvement. PMID- 3334202 TI - Tourette syndrome: recent advances. AB - In spite of new information relevant to the clinical and biological features of Tourette syndrome, areas of controversy still exist. A genetic substrate is present in at least some affected families; there also is clearly a genetic relationship between Tourette syndrome and chronic motor tic disorder. Patients with Tourette syndrome have an increased incidence of behavior problems, attention deficit disorder, and obsessive-compulsive symptoms. Treatment of the attention deficit disorder with psychostimulant drugs will exacerbate tics in some patients. Haloperidol remains the most consistently useful therapeutic agent. Pimozide and clonidine also may be useful, but further work is required before standard treatment protocols can be developed. The disorder most likely results from dysfunction of dopaminergic systems. PMID- 3334203 TI - Neurologic syndromes in hyperammonemic disorders. AB - This article reviews the neurologic manifestations of hyperammonemic disorders. A variety of inborn errors of metabolism, as well as transient neonatal or acquired hepatic dysfunctions, are identified as causes of hyperammonemia. The pathogenesis of hyperammonemia in these disorders is outlined. Catastrophic hyperammonemia and hyperammonemic coma are described; algorithms to establish specific diagnosis are suggested. Symptoms of less severe ammonia intoxication, which also occur in more common diseases, are described. The need to consider hyperammonemia as a potential etiology for these symptoms is emphasized. Finally, the neurotoxicity of ammonia is discussed. PMID- 3334204 TI - Demonstration in children of oligoclonal IgG bands in unconcentrated CSF using agarose isoelectric focusing and immunolabeling. AB - Agarose isoelectric focusing, followed by protein transfer to cellulose nitrate membrane and double-antibody avidin-biotin peroxidase staining (avidin-biotin agarose isoelectric focusing), was used to demonstrate oligoclonal IgG bands in unconcentrated cerebrospinal fluid (CSF) and serum; 161 consecutive pediatric patients, ages 6 months to 16 years with a variety of mainly neurologic disorders, were studied. The procedure was standardized for agarose isoelectric focusing (AIF) using 5 microliter specimens containing 125 ng of IgG. Oligoclonal bands were found in the CSF of 12% of the patients; bands were found simultaneously in the CSF and serum of 10% of the patients, mostly those with nervous system infections, but also those with central nervous system tumors, seizures, or migraine. In about 50% of positive cases, oligoclonal bands constituted the only CSF abnormality, reflecting an abnormal humoral immune response within the CSF-central nervous system compartment. Avidin-biotin AIF can be recommended as an integrated part of routine CSF examinations in children. PMID- 3334205 TI - Megalencephaly: types, clinical syndromes, and management. AB - The differential diagnosis of megalencephaly poses a challenge to the clinician. The two major categories, metabolic and anatomic, include a number of conditions, many of them rare. This article provides a systematic approach to the patient with megalencephaly. PMID- 3334206 TI - Total and local bone mineral during estrogen treatment: a placebo controlled trial. AB - 103 healthy postmenopausal women with a natural menopause 0.5-2 years previously were randomized to either estrogen (n = 52) or placebo (n = 51) treatment. Total body bone mineral (TBBM) was measured by dual photon absorptiometry and forearm bone mineral content (BMC) by single photon absorptiometry before and after one year. Both TBBM and forearm BMC fell significantly (P less than 0.001) in the placebo group, but were unchanged after estrogen treatment. The loss of bone mineral in the placebo group during one year was 5% (TBBM) and 3% (forearm BMC). A significant correlation (r = 0.53; P less than 0.001) was found between the fractional percent change in forearm BMC and TBBM. It is concluded, that both the forearm BMC and the TBBM measurements are suitable for following changes in bone mass postmenopausally. The almost equal relative amount of cortical bone in the total skeleton and in the forearm BMC may explain that longitudinally performed forearm BMC measurements are indicative of average changes in the total skeletal status. PMID- 3334207 TI - Effect of 1 alpha (OH)-vitamin D3 on insulin secretion in diabetes mellitus. AB - Fourteen non-insulin-dependent diabetic subjects were placed on a balanced diet for 2-3 weeks followed by the same balanced diet alone (group I: control, n = 7) or daily administration of 1 alpha (OH)-vitamin D3 (1 alpha (OH)D3) (group II: 2 micrograms/day, n = 7) additionally for the next 3 weeks. A 75 g oral glucose loading test was conducted before and after the experiment and the plasma insulin response was compared along with the metabolic parameters including serum calcium, phosphorus and serum lipids. The following results were obtained. (1) Total insulin secretion in response to 75 g glucose loading was significantly increased in group II (16.3 +/- 3.9 microU/2 h/ml versus 22.7 +/- 4.9 microU/2 h/ml; P less than 0.05), though no difference was demonstrated in group I. (2) Mean serum calcium level was significantly increased from 9.4 +/- 0.1 mg/dl to 9.6 +/- 0.1 mg/dl (P less than 0.05) and serum free fatty acid level was decreased from 0.80 +/- 0.07 mEq/l to 0.53 +/- 0.07 mEq/l (P less than 0.05) in group II, but not in group I. (3) However, there was no direct correlation between total insulin secretion during a 75 g oral glucose loading test and serum calcium or free fatty acid level. The findings that 1 alpha (OH)D3 enhances insulin secretion and reduces the levels of serum free fatty acid in non-insulin dependent diabetics provide us with the possibility that vitamin D may play some role in the regulation of insulin secretion. PMID- 3334208 TI - Bone particles from toothless (tl/tl) osteopetrotic rats not cured by bone marrow transplantation are resorbed in normal littermates. AB - We examined the possibility that the failure of toothless (osteopetrotic) rats to be cured by bone marrow transplantation from a normal littermate is due to the production of poorly resorbable bone. Mineralized bone particles from mutants (tl/tl) and normal littermates were implanted subcutaneously in normal rats of this stock. The removal of bone and recruitment of multinucleated giant cells were evaluated by histomorphometry. No differences were found between mutant and normal bone from this stock or from two other osteopetrotic rat stocks, incisors absent and osteopetrosis, known to be cured by bone marrow transplantation. Subject to the limitations of this method, these data suggest that the failure of tl/tl rats to be cured by bone marrow transplants from normal littermates is not due to the production of unresorbable bone or a bone matrix deficient in its ability to recruit multinucleated giant cells and presumably osteoclasts. PMID- 3334209 TI - [Retinoids. Modern pharmaco-biological findings and clinical experience]. PMID- 3334210 TI - [In remembrance of Professor Bohuslav Polak]. PMID- 3334211 TI - Neurophysiology of rheumatic pain. PMID- 3334212 TI - The place of the pain clinic. AB - Chronic pain is a debilitating and degrading condition. Its aetiology is largely multifactorial, and only proper appreciation of the various factors which can combine to produce the patient's misery will allow appropriate therapies. If the mechanisms of chronic pain were better taught and the therapies available were better used by medical practitioners, then the standard of alleviation of pain would increase greatly. There is an urgent need for greatly improved facilities for treating chronic pain by multidisciplinary groups in specialized clinics, a fact which has been realized for over 30 years. However, in spite of this there is a great delay in the setting up of such units. There is also an urgent need for proper training of doctors in pain relief, and a need for a much larger amount of money to be spent on research into the causes and treatment of human pain. It is disturbing to me that so much money goes on research into possible cures of malignant disease in the future, which is all very well, but which does not help the sufferer from severe pain at the present time; whereas these poor unfortunates, dying with their misery unassuaged, must suffer unnecessarily because of lack of information amongst physicians, and lack of proper facilities for treatment. Likewise, our own unit and many others have extremely long waiting lists, making even more difficult the treatment of an already complex problem. In spite of this, more than 50% of patients who attend multidisciplinary pain clinics obtain long-term benefit from their therapy. The fact that facilities do not exist for many sufferers is not only disgraceful, but also very expensive both from social security payments and from inappropriate use of health care facilities as these patients wander from clinic to clinic in search of a cure which is not available. Chronic pain should be recognized for what it is--a severe and debilitating condition--and proper steps should be taken to provide the treatment within the health service for its alleviation. PMID- 3334214 TI - Physiotherapy methods of relieving pain. AB - Management of pain in the person with arthritis requires interdisciplinary team work with the patient being the final manager. It is important that any health care provider perceive the patient as a person who happens to have arthritis--not as 'an "arthritic".' Defining a person by one's disease process is dehumanizing. The patient has the same aspirations as anyone who is ablebodied--to be free from disease. While the patient may know that a cure is not imminent, there is still the hope for one. Therefore, as the patient comes for physiotherapy, there may be a hidden wish that the moist packs, TENS, or therapeutic pool will be curative. It is important that the patient understand that no equipment in the physiotherapy department has curative powers. This will help avoid unnecessary dependency behaviours on the part of the patient. Careful instruction and supervision of the patient by the physiotherapist, in concert with reinforcement from the physician, can prepare the patient to apply heat, cold, or a variety of treatments at home. Although the patient is given the responsibility for this part of his care, periodic follow-up and reassessment should be completed to determine changes in his physiological, psychological, and functional status. Physiotherapists who have a clear understanding of the physical treatment of pain associated with the rheumatic diseases can be a valuable asset to medical care. PMID- 3334213 TI - The surgical management of pain. PMID- 3334216 TI - Endogenous opioids. PMID- 3334215 TI - Psychiatric aspects of pain and their treatment. PMID- 3334217 TI - The measurement of pain. PMID- 3334218 TI - Drug treatment of pain in rheumatoid disorders. AB - The relief of pain remains a delicate balance between the potential toxicity and desired effect of currently available compounds. Physician and patient need to make the optimum use of such therapies. Control of pain and stiffness in rheumatic diseases is a dynamic process. There is a constant need for re appraisal of aims and objectives and adjustment of treatment according to variations in disease and response. Where 'specific' therapy is available, it is clearly preferable to use it rather than employ large doses of purely symptom relieving drugs. At present toxicity is inextricably linked to efficacy, and dissociation of these two factors seems unlikely to be achieved in the near future. More efficient 'targeting' of drugs at the site of desired action should help to minimize the adverse effects of therapy. Ultimately the most efficient way of relieving pain and stiffness will be to prevent or suppress the inflammatory disorders which give rise to the symptoms. Unfortunately this is an elusive goal at present. PMID- 3334219 TI - Sleepiness in shiftwork. A review with emphasis on continuous monitoring of EEG and EOG. AB - Many forms of shift work disrupt the normal relation between rest/activity and the circadian regulation of bodily functions (1). Among the most obvious effects of this disruption is disturbed sleep and increased sleepiness (2, 3). Here we will discuss the effects on sleepiness. Much of the data in this area consist of self-ratings but our emphasis will be on some recent approaches that have made use of EEG methods to provide continuous monitoring of fluctuations of sleepiness in freely moving subjects. PMID- 3334220 TI - Circadian and seasonal variations of plasma insulin and cortisol concentrations in the Syrian hamster, Mesocricetus auratus. AB - Circadian rhythms of plasma insulin, cortisol, and glucose concentrations were examined in scotosensitive (reproductively sensitive to inhibitory effects of short daylengths) and scotorefractory male and female Syrian hamsters (Mesocricetus auratus) maintained on short (LD 10:14) and long (LD 14:10) daylengths. The baseline concentration (mean of all values obtained every 4 hr six times of day) of insulin was much greater in female than in male scotosensitive hamsters kept on short daylengths. These differences in insulin concentration may account for the observed heavy fat stores in female and low fat stores in male scotosensitive hamsters kept on short daylengths. The baseline concentrations of cortisol were approximately equal in both scotosensitive and scotorefractory males held on short and long daylengths, but were relatively low in females held on short daylengths and especially high in scotorefractory females held on long daylengths. The plasma concentrations of both cortisol and insulin varied throughout the day in many of the groups tested. However, the variations were not equivalent. The circadian variations of cortisol were similar irrespective of sex, seasonal condition and daylength. Peak concentrations generally occurred about 12 hr after light onset. In contrast, the circadian variations of insulin differed markedly. For example in male hamsters, robust daily variations were found in scotosensitive hamsters held on short daylengths but not on long daylengths and in scotorefractory hamsters held on long daylengths but not on short daylengths. Furthermore, the daily peak occurred during the light in the scotosensitive hamsters and during the dark in the scotorefractory animals. Neither the daily feeding pattern (about 60% consumed during dark) nor the daily variations of glucose concentration varied appreciably with seasonal condition or daylength. They do not appear to determine nor directly reflect the variations in cortisol and glucose concentrations. It is postulated that the daily rhythms of cortisol and insulin are regulated by different neural pacemaker systems and that changes in the phase relations of circadian systems account in part for seasonal changes in body fat stores. PMID- 3334221 TI - Light and melatonin as zeitgebers in man. PMID- 3334222 TI - "A clinical trial of topical nucleic acid and lipoprotein complex in treatment of herpes simplex keratitis". PMID- 3334223 TI - Results of penetrating keratoplasty with cataract extraction and intraocular lens implantation in Fuchs' dystrophy. AB - Combined procedure was performed in 25 eyes and triple procedure in 32 eyes of Fuchs' dystrophy. Pre-operative visual acuity was 20/100 or less in 63.2% of eyes. The graft was clear in 76% of combined procedure and in 97% of triple procedure eyes. Post-operative visual acuity of 20/40 or better was obtained in 57.9% of eyes. The common cause of graft failure was allograft reaction. The other causes attributable to visual failure were opacification of posterior capsule, secondary glaucoma, macular degeneration and pre-existing glaucomatous cupping. Intraocular lens insertion at the time of surgery helps in rapid visual rehabilitation. PMID- 3334224 TI - Triple procedure of penetrating keratoplasty, extra capsular cataract extraction and posterior chamber I.O.L. implantation. AB - Ten cases of triple procedure of PKP, ECCE with IOL implantation have been presented and there results discussed. PMID- 3334225 TI - Keratoplasty in complicated radial keratotomy cases. PMID- 3334226 TI - Keratoplasty for complicated leucomas. AB - Fifty cases of complicated leucomata in which keratoplasty was done during the last two years, are analysed. Although complicated cases yield not so good optical result, the results are much improved by proper pre-operative, operative and post-operative management. PMID- 3334227 TI - Results of epikeratoplasty. PMID- 3334228 TI - Morphologic features of clear and failed epikeratophakia lenticules. PMID- 3334229 TI - Dr. P. Siva Reddy Oration. Refractive keratoplasty. PMID- 3334230 TI - Roper Hall F.B. locator and ultrasonic evaluation of intra ocular foreign bodies. PMID- 3334231 TI - Ultrasonography in aetiological diagnosis of leucocoria. PMID- 3334232 TI - Diagnostic radiology in disaster medicine: implications for design, planning and organization of X-ray departments. AB - Diagnostic radiology plays an important role in the evaluation of disaster casualties; these are referred to X-ray departments, shortly after their arrival at hospital, in large numbers, frequently overwhelming facilities and resources of the department. The study of relevant literature and the experience of the authors suggest that there are implications for design, planning and organization of X-ray departments to be considered in disaster-prone areas. Departments should be sited as near as possible to triage areas, on the same floor, with broad, unobstructed passages. There should be provision for easy passage of equipment and trolleys through doors and corridors and large circulation areas, working rooms and waiting spaces with plugs, for electricity, piped oxygen and suction and devices for hanging infusion sets. Two entrances to the department would enable one-way flow through the department. All work should be done in the department and examinations performed with mobile units avoided. A radiologist at the entrance to the department and a control post at the exit ensure adequate processing of casualties. Interpretation and reporting should be done by assigned radiologists dictating directly to typists; films and reports should accompany casualties. PMID- 3334233 TI - The Pipkin fracture-dislocation of the hip. AB - The 'Pipkin' fracture-dislocation of the hip is an injury that is easily missed and is associated with serious sequelae. Eighty posterior dislocations of the hip were studied; there were nine 'Pipkin' injuries, seven of which are reported. The aetiology and management is discussed and the literature is reviewed. Guidelines for management are suggested. PMID- 3334234 TI - The use of controlled tissue expansion for secondary reconstruction in injury. PMID- 3334235 TI - A controlled prospective study of early mobilization of minimally displaced fractures of the distal radial metaphysis. AB - A controlled prospective trial of early exercise of slightly displaced fractures of the distal radial metaphysis has been performed. Twenty-eight fractures were enclosed in a tubigrip support 7-13 days after injury and 28 fractures were splinted in below-elbow plaster for 4 weeks. It was found that early movement of the wrist produced a superior functional result at 5 and 7 weeks (P less than 0.05) and allowed an earlier recovery of domestic skills (P less than 0.05). Early exercise did not improve recovery of strength of grip and did not produce a higher incidence of malunion. Patients treated in tubigrip experienced no more pain in weeks 4 and 6 and apart from one failure, no patient actively disliked this form of treatment and 22 were totally satisfied. PMID- 3334236 TI - Treatment of fractures of the hallux with a simple splint. AB - Three hundred patients with fractures of the hallux were randomly treated with either a short plantar splint or spica strapping in a prospective crossover trial. The results showed that more patients preferred the splint and the mean pain score was lower in the group treated with a splint (P less than 0.001). It is concluded that the splint is a cheap and effective method of treatment of fractures of the hallux. PMID- 3334237 TI - The contribution of Ruscoe Clarke and his team to knowledge relevant to blood loss after injury. AB - The major contributions of Ruscoe Clarke, made between 1947 and 1959 at the Birmingham Accident Hospital, are recalled. He and his team measured the red cell volumes. By these and other means we estimated the average blood loss from a series of civilian injuries. It was found that the lowest haemoglobin level 4-14 days after injury was a useful clue in retrospect of the degree to which blood lost had been replaced by blood transfusion. We showed that early transfusion of the correct volume of whole blood appeared to lead to the best chance of quick and full recovery from serious injury. We stressed the need to assess the blood transfusion requirement more precisely. PMID- 3334238 TI - Treatment of fresh tears of the anterior cruciate ligament. A comparison of primary suture and augmentation with carbon fibre. AB - Early results after a follow-up of 1 year of primary suture and carbon fibre augmentation in the treatment of fresh anterior cruciate ligament tears in 57 consecutive and randomized patients are presented. There was no statistical difference between the two groups in the postoperative course. At an average of 13 months follow-up, complete stability was achieved regarding the pivot shift sign in 16 (55 per cent) and 18 (75 per cent) of the sutured and augmented groups respectively. There were 3/29 obvious pivot shifts in the sutured and 1/24 in the augmented knees. Seventeen carbon fibre reinforced knees were postoperatively arthroscoped at the 1-year follow-up. A structure resembling a 'neoligament' was observed in 8/16 knees. In 11 knees there were no signs of carbon material, in 4 knees subsynovial microparticles were scattered around the anterior compartment and in 3 knees the carbon fibre tow was bare in the joint despite careful covering within the ligament remnants at the time of the operation. Although no statistical difference was obtained between the two groups the augmentation procedure seemed to improve stability at the 1-year follow-up. PMID- 3334239 TI - Use of ultrasound scanning in diagnosis and conservative management of rupture of the spleen. PMID- 3334240 TI - Conjugated alpha-keto acids as mechanism-based inactivators of brewer's yeast pyruvate decarboxylase: electronic effects of substituents and detection of a long-lived intermediate. AB - A series of phenyl substituted E-4-phenyl-2-keto-3-butenoic acid derivatives were synthesized (p-Cl, m-Cl, p-NO2, m-NO2, o-NO2, 3,4-Cl2, 2,6-Cl2, p-CH3O, p (CH3)2N) and tested as potential irreversible inhibitors of brewer's yeast pyruvate decarboxylase (EC 4.1.1.1). All those derivatives with electron withdrawing substituents were found to be time-dependent inactivators of the enzyme, unlike the p-CH3O- and p-(CH3)2N derivatives. Detailed kinetic studies with the m-nitro derivative (the most potent inhibitor) indicated that this compound formed reversible complexes with the enzyme at two sites (supposed regulatory and catalytic with Ki values of 0.026 and 0.13 mM, respectively) prior to irreversible inactivation of the enzyme. In addition, concurrently with the inactivation, addition of the m-NO2 derivative to the enzyme produced a new VIS absorbance with lambda max near 430 nm. This absorbance was attributed to the enzyme-bound enamine intermediate. The time course of formation and disappearance of the intermediate could be determined and provided detailed information about the mechanism of the enzyme. PMID- 3334241 TI - Interaction between L-aspartic acid and L-asparaginase from Escherichia coli: binding and inhibition studies. AB - Experiments using equilibrium dialysis and fluorescence quenching provided direct evidence that approximately four moles of L-aspartic acid were bound per mole of tetrameric L-asparaginase from Escherichia coli, with a dissociation constant on the order of 60-160 microM. In addition, a set of weaker binding sites with a dissociation constant in the millimolar range were detected. Kinetic studies also revealed that L-aspartic acid inhibited L-asparaginase competitively, with an inhibition constant of 80 microM at micromolar concentrations of L-asparagine; at millimolar concentrations of the amide, an increase in maximal velocity but a decrease in affinity for L-asparagine were observed. L-Aspartic acid at millimolar levels again displayed competitive inhibition. These and other observations suggest that L-aspartic acid binds not only to the active site but also a second site with lower intrinsic affinity for it. The observed "substrate activation" is most likely attributable to the binding of a second molecule of L asparagine rather than negative cooperativity among the tight sites of the subunits of this tetrameric enzyme. Further support for L-aspartic acid binding to the active site comes from experiments in which the enzyme, when exposed to various group-specific reagents suffered parallel loss of catalytic activity and in its ability to bind L-aspartic acid. Different commercial preparations of Escherichia coli L-asparaginase were found to contain approximately 2-4 moles of L-aspartic acid; these were incompletely removed by dialysis, but could be removed by transamination or decarboxylation. Efficiency of dialysis increased with increasing pH. Taken together, this set of results is consistent with the existence of a covalent beta-aspartyl enzyme intermediate. PMID- 3334242 TI - Structure-activity relationships amongst beta-lactamase inhibitors. AB - Using a variety of beta-lactamases including those from Escherichia coli (TEM-1), Enterobacter cloacae P99 and Staphylococcus aureus the inhibition profiles (I50 values) were determined for various groups of compounds including penicillins, penicillanic acid derivatives (sulphone and beta-halo substitutions), olivanic acids and clavulanic acid derivatives including substituted ethers and amines. Some of the latter compounds had higher activity than clavulanic acid with and without preincubation of enzyme with inhibitor but they still had poor activity against the P99 enzyme. Improvements in activity against Class I cephalosporinases were obtained with some derivatives of clavulanic acid but this was usually achieved at the expense of activity against clavulanate susceptible beta-lactamases. The olivanic acids had the highest activity against the widest range of beta-lactamases. PMID- 3334243 TI - Inhibitors of renin as potential therapeutic agents. PMID- 3334244 TI - Further inhibition studies on guanidinobenzoatase, a trypsin-like enzyme associated with tumour cells. AB - Guanidinobenzoatase is a proteolytic enzyme capable of degrading fibronectin and is a tumour associated enzyme. Guanidinobenzoatase has been shown to be an arginine selective protease and is distinct from trypsin, plasminogen activator, plasmin, thrombin and a newly described tumour associated enzyme specific for guanidino phenylalanine residues. These conclusions have been derived from inhibition studies employing 4-methyl-p-guanidinobenzoate as substrate. Three active site titrants for trypsin have been shown to be good substrates for guanidinobenzoatase. A new active site titrant for trypsin, rhodamine bisguanidinobenzoate, can also be used to assay guanidinobenzoatase in a stoichiometric manner. This active site titrant can be employed to label guanidinobenzoate on the surface of leukaemia cells. PMID- 3334245 TI - Fluorescent inhibitors of a cell surface protease used to locate leukaemia cells in kidney sections. AB - Guanidinobenzoatase is a trypsin-like protease on the surface of cells capable of migration, for example leukaemia cells. We have used a number of fluorescent probes that are competitive inhibitors of guanidinobenzoatase to locate leukaemia cells in resin sections of kidney tissue obtained from leukaemic rats. We have demonstrated how this competitive inhibition system can be used to direct desired molecules (such as cytotoxic drugs) to these cells and to monitor the arrival of such compounds at the active site of guanidinobenzoatase. The principles developed in this study could equally well be applied to other enzymes on other cells provided suitable competitive inhibitors were designed. The presence of an enzyme on the surface of a cell can be used to direct molecules to that cell provided that these molecules contain a functional group that acts as an inhibitor for the chosen enzyme. PMID- 3334246 TI - A comparative analysis of the synergistic interaction between N1 phenylsulfanilamides and benzylpyrimidines using qsar techniques. AB - Growth inhibition of E. coli cell culture has been determined for a series of 4 substituted-N1-phenylsulfonilamides tested in the presence and absence of synergistic concentrations of trimethoprim. Quantitative structure-activity relationships, established by regression analysis, exhibit an identical dependence of bacterial growth inhibition on sulfonamide pKa irrespective of the presence or absence of trimethoprim. Examination of a small series of benzylpyrimidines in the presence or absence of 4-dimethylamino-N1 phenylsulfanilamide gave similar results. Since the presence of a synergistic agent affords no change in structure-activity relationships, it is concluded that no direct interaction between sulfonamides and benzylpyrimidines occurs and that the synergism observed is solely the result of the kinetic consequences of sequential blockade of the folate biosynthetic pathway. PMID- 3334247 TI - Elastase inhibitors for treatment of emphysema. Approaches to synthesis and biological evaluation. PMID- 3334248 TI - [New imaging technique for the cardiovascular system: introduction to DSA]. AB - This introduction to digital subtraction angiography (DSA) was presented before the presentations of the panelists. DSA is a new imaging procedure for evaluating cardiovascular disease, images with successful digitization of X-ray picture achieved following the development of CT. DSA is less invasive than ordinary angiocardiography; it features real time imaging, good spatial and temporal resolution, and the capability of providing functional and anatomical information. Although DSA has been applied mainly to the vascular system, its use is being extended to the evaluation of ischemic heart disease. One disadvantage of DSA consists of misregistration artifacts which are caused by temporal subtraction technique. In attempts to overcome this disadvantage, energy subtraction, hybrid subtraction, and the application of a matched filter technique have been investigated. The recent development of angiographic contrast media with low osmolarity will serve to extend the indications for DSA. PMID- 3334249 TI - [Cardiovascular involvement in the aortitis syndrome: a study using digital subtraction angiography]. AB - Cardiovascular involvement in 22 cases with clinically confirmed aortitis syndrome was assessed using digital subtraction angiography (DSA) with an ADAC DPS-4100 system added to Siemens Angioskop A. The aorta and its branches, and the pulmonary vessels were examined for the extent, severity, and type of involvement. Left ventriculography was also performed for all patients. Digital subtraction angiograms of diagnostic quality were obtained in all the patients. Significant arterial narrowing was demonstrated by DSA in at least one vascular segment of each patient. DSA showed 32 total and 43 subtotal occlusions in 484 segments. DSA also imaged aneurysmal dilatation of the aortic root in one patient; an aneurysm of the innominate artery in two; a large anastomotic vessel connecting the superior and inferior mesenteric arteries in three; diffuse hypokinesis of the left ventricular wall in one; and stenosis of the pulmonary arterial branches in four patients. Clinical symptoms and signs did not correlate closely with the findings of DSA. It is concluded that the radiographic imaging of DSA is adequate and can be used to replace that of conventional angiography in evaluating the aortitis syndrome. PMID- 3334250 TI - [Quantitative analysis of the left ventricular volume curve by digital subtraction angiography]. AB - Digital subtraction angiography (DSA) not only permits visualizing the left cardiac and arterial systems after injecting contrast media intravenously, but enables quantitative and functional analyses of the data collected. This report describes our experiences with several videodensitometric analyses for assessing global and regional left ventricular (LV) functions. 1. Analyses of LV volume curves with contrast media In the conventional cineventriculogram, construction of LV volume curves by the area-length method requires tedious efforts, but with DSA, such curves are provided automatically using videodensitometric analyses. The advantages of the DSA method include; 1) DSA has better contrast resolution than radionuclide angiography. 2) The densitometric technique may offer more accurate results than methods based on geometric assumptions, especially when the LV shape is irregular or when it changes during a single cardiac cycle. 2. Analyses of LV volume curves without contrast media Computer analyses of DSA images without contrast media facilitated the noninvasive evaluation of global and regional LV functions. The method is based on the ability to detect small differences in X-ray absorption by the cardiac silhouette during a single cardiac cycle, without any contrast media. We applied this capability to Fourier analysis using radionuclide angiographic computer programs and succeeded in evaluating regional wall motion abnormalities in patients anterior myocardial infarction. In summary, the videodensitometric analysis of the DSA image is a promising new approach for the clinical of LV function, due to its combined capability of automated computerized analysis similar in radionuclide study, and due to higher contrast resolution just like as LV cineangiography. PMID- 3334251 TI - [Present status and future of real-time two-dimensional Doppler echocardiography]. AB - Advent of Doppler echocardiography has provided a great number of informations regarding the intracardiac blood flows. However, conventional pulsed Doppler echocardiography using fast Fourier transform is cumbersome and time-consuming for intracardiac flow imaging despite the capability of localizing the sample volumes in the two-dimensional echocardiograms. Recently, real-time two dimensional Doppler echocardiography (color flow mapping) has come into clinical practice and made a breakthrough in the diagnosis of cardiovascular disease. Color flow mapping is divided into two different displays; the one is velocity display and the other power display. In velocity display, the direction and magnitude of the mean flow velocity and the spectrum variance are displayed in color, being superimposed on the two-dimensional images in real-time. The flow toward the transducer is depicted as a red color and away from the transducer as a blue color. The velocity spectrum variance represents the turbulence by adding green to red and blue. Additionally, the magnitude of the velocity is displayed by the brightness of color. In power display, the sum of the squared amplitude of the reflected echo signals from blood cells is depicted as red or blue when the flow is directed or away from the transducer, regardless of the velocity. However, this display lacks the display of velocity spectrum variance. Nevertheless, the merits of this display consists in the capability of describing the slower blood flows in wider areas of enlarged chambers. Furthermore, it may have a lower dependence on the incidence of the ultrasonic beams.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3334252 TI - [Assessment of myocardial perfusion using digital subtraction angiography]. AB - To assess myocardial perfusion, intra-aortic digital subtraction angiography (IADSA) was performed. Functional images are generated by taking a series of myocardial enhancement images. For each pixel, maximum density of enhancement (Cmax), integrated enhancement area under the curve (Cinteg), mean transit time (MTT) and Cmax/MTT or Cinteg/MTT were extracted. DSA was applicable for evaluating myocardial perfusion in patients with ischemic heart disease. PMID- 3334253 TI - [Digital subtraction angiography of the coronary artery: evaluation of morphological aspects]. AB - The usefulness of digital subtraction angiography (DSA) in coronary angiography was evaluated in terms of its ability to delineate the coronary artery and aortocoronary (A-C) bypass grafts. First, 59 intra-arterial injections of contrast media were made for 23 patients with ischemic heart disease. With aortic root injection, the proximal coronary artery was moderately well visualized, but visualization of the peripheral arteries was inadequate. By selective coronary injection, good images of the coronary arteries were obtained using small quantity of contrast media; however, detailed evaluations of the degrees of stenosis and collateral circulation were difficult, because of limitations in spatial resolution and misregistration artifacts due to cardiac pulsations. In addition, the patencies of 12 A-C bypass grafts were evaluated using intravenous (IV-) DSA for three cases and intraaortic (IA-) DSA for five cases. Ten grafts were shown to be patent. With IV-DSA, the graft was imaged as superimposed on the ascending aorta. In IA-DSA, a small (4F) catheter was introduced via the right brachial artery and advanced to the ascending aorta where an aortic root injection was performed. With aortic root injection, not only the anastomotic portion but also the distal native coronary artery were visualized. Lateral and severe left anterior oblique projections were best to visualize the grafts. IA DSA using 4F catheter could be performed for outpatients without complications. The patency of a graft can be evaluated with the time density curve between two points in the graft, and the coronary blood flow can be calculated using the time density curve measurements and the diameter of the artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3334254 TI - [Positron emission computed tomography]. AB - Positron emission computed tomography (PET) provides high quality tomographic images of the heart with accurate attenuation correction. The use of various compounds labeled with ultra-short lived positron-emitting radionuclides, such as 11C, 13N, 15O and 18F, allows physiological and biochemical measurements in vivo. Recently, a few institutions in Japan have introduced this technique into cardiology. Although it requires an enormous cost both for the equipment and for running the system, it is expected to play a major role in nuclear cardiology in the near future. PMID- 3334255 TI - [Urinary tract reconstruction]. PMID- 3334256 TI - [Bladder cancer--basic and clinical studies of its occurrence, invasion and metastasis]. PMID- 3334258 TI - [Relation of innervation and function of the lower urinary tract]. PMID- 3334257 TI - [An ileal conduit and associated operative procedures]. PMID- 3334259 TI - [Photodynamic therapy of urologic cancer]. PMID- 3334260 TI - [Adsorption of Saccharomyces cerevisiae cells by carbon sorbents]. PMID- 3334261 TI - [Pathogenic properties of Aspergillus fumigatus Fres]. PMID- 3334262 TI - [Use of substances of microbial origin as components of detergent-disinfectant agents]. PMID- 3334263 TI - [The centenary of the organization of the Odessa Bacteriological Station]. PMID- 3334264 TI - [The viability of Escherichia coli in samples of water from rivers and artificial reservoirs]. PMID- 3334265 TI - [Antimicrobial properties of surface-active antiseptic agents--polymethylene diamine derivatives]. PMID- 3334266 TI - [Comparative characteristics of the antimicrobial activity of essential oils]. PMID- 3334267 TI - [A nutrient medium for isolating proteases of bacteria of the genus Bacillus]. PMID- 3334268 TI - [Polybiotrophy of bacteria of the genus Klebsiella]. PMID- 3334269 TI - [Experimental fumigatotoxicosis in mink]. PMID- 3334270 TI - [Virulence plasmids of pathogenic enterobacteria]. PMID- 3334272 TI - [Benchmark memorial medal dedicated to Avgust Kirkhenshtein (1872-1963)]. PMID- 3334271 TI - [Antibiotic resistance of pathogenic Escherichia coli isolated from patients and bacterial carriers]. PMID- 3334273 TI - [Vasilii Leonidovich Omelianskii]. PMID- 3334274 TI - Divorce: its impact on children. PMID- 3334275 TI - The assaulted nurse: strategies for healing. PMID- 3334276 TI - "Wounded womanhood." An analysis of Karen Horney's theory of feminine psychology. PMID- 3334277 TI - Women in grief. PMID- 3334278 TI - Dealing with divorce: a group therapy intervention for women. PMID- 3334279 TI - [Effect of desiccation of triatoma feces on the survival of metacyclic forms of Trypanosoma cruzi]. PMID- 3334280 TI - The palm tree Copernicia cerifera (carnauba) as an ecotope of Rhodnius nasutus in rural areas of the state of Piaui, Northeastern Brazil. PMID- 3334281 TI - [Effect of digestive juices on the absorption and destination of oral BCG vaccine]. PMID- 3334282 TI - [Labrea hepatitis: a characteristic histological picture?]. PMID- 3334283 TI - Silicone and rheumatic diseases. AB - Silicone generally has been regarded as a biologically inert material. However, recent reports suggest that inflammatory responses to silicone occur. There is some experimental and clinical evidence of a direct inflammatory response to the presence of liquid or particulate silicone. These include granulomatous skin reaction to injected silicone, synovitis around silicone prosthetic joints, and lymphadenopathy proximal to silicone prostheses. There are case reports of systemic rheumatic disease following silicone prostheses, but no definitive proof of a direct relationship between silicone prostheses and systemic disease. The clinical features of the reported cases following breast augmentation include breast tenderness, axillary adenopathy, sclerodermatous skin changes, arthritis, Raynaud's phenomenon, rheumatoid factors, and ANAs. Prior epidemiologic evidence and the number and consistency of our own and others' clinical findings suggest that silicone may indeed be associated with inflammatory processes and rheumatic diseases. PMID- 3334284 TI - Cardiovascular involvement in systemic lupus erythematosus. AB - SLE is an inflammatory disease of unknown etiology with the potential of affecting virtually all organ systems. Cardiovascular involvement occurs frequently, although it is often mild enough not to cause clinical concern. Pericarditis is most commonly subclinical, noted only on echocardiogram. Pericardial fluid, which can accumulate rapidly enough to cause tamponade, is inflammatory in nature and can totally mimic infection. The occurrence of Libman Sacks endocarditis, usually a pathological diagnosis of little clinical significance, has little if any correlation with the presence of audible murmurs. However, valve replacement is occasionally necessary secondary to sterile destruction. These valvular lesions can also embolize or become infected. The incidence of ischemic coronary disease is increased, both secondary to premature atherosclerosis and, rarely, coronary arteritis. Conduction disease and arrhythmias are infrequently reported in adult patients, but congenital CHB has been noted in children born to mothers who have circulating anti-Ro antibody. Evidence is accumulating that suggests there is a mild cardiomyopathy associated with SLE that may be due to thrombotic or inflammatory microvascular coronary disease. Acute clinical myocarditis also rarely occurs. Therapeutically, at present, a reasonable course would seem to be to limit all known possible contributing factors to premature coronary artery and myocardial disease (hypertension, hypercholesterolemia, smoking, steroid therapy, etc), to be vigilant about recognizing the rarer complications associated with SLE (infectious pericarditis and endocarditis, coronary arteritis, pericardial tamponade, clinical myocarditis), and to remember that these uncommon complications are indeed uncommon. The importance of vigorously treating systemic hypertension cannot be overstressed. PMID- 3334285 TI - Stress and rheumatoid arthritis: can a cognitive coping model help explain a link? PMID- 3334286 TI - Rheumatic manifestations of diseases associated with substance abuse. AB - Rheumatic manifestations of substance abuse are uncommon but recognized complications. Repeated injections of drugs and adulterants represent repeated antigenic challenge. The population at greatest risk is that of young males, although females with eating disorders are more apt to develop myopathy, clubbing, or periostitis. Alcohol, the most common substance abused, is associated more often with myopathy. In IV drug abusers, hepatitis B viral infection, bacterial endocarditis, primary skeletal infections, and venous complications are most common in that order. However, the spectrum may evolve as the pattern of substance abuse changes. First, the frequency of cocaine dependence is rapidly approaching that of alcohol. Two regular cocaine users are reported as having Raynaud's phenomenon and abnormal serologies. Second, synthesis of lookalike drugs may produce new associations, such as parkinsonism after IV N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Third, the increased use of ipecac and purgatives in eating disorders is an important consideration in young women with otherwise unexplained myopathy or arthritis. Finally, patients with AIDS are presenting with autoimmune phenomena or a spectrum of unusual infections that change as the epidemic evolves. Increased recognition of these symptom complexes may lead to earlier, more accurate diagnoses and avoidance of unnecessary diagnostic evaluations and delays in treatment. PMID- 3334287 TI - [Comparative evaluation of the clinical effects of root scaling with and without local anesthesia]. PMID- 3334288 TI - [Analysis of different types of alloys for construction of hollow posts]. PMID- 3334289 TI - [The use of silicone rubber for borders and basing of removable dentures]. PMID- 3334291 TI - [Fluorine toxicity in fluoride prophylaxis]. PMID- 3334292 TI - [Endorbital foreign bodies: report of a case]. PMID- 3334290 TI - [The importance of the Maryland bridge in orthognathodontics]. PMID- 3334293 TI - [Characteristics of the development of oral surgery in Celje]. PMID- 3334294 TI - [Review of anesthesiologic activities in oral and maxillofacial surgery]. PMID- 3334295 TI - [Cytodiagnosis of the thyroid and parathyroid glands]. PMID- 3334296 TI - [Cytodiagnosis of the lymph nodes]. PMID- 3334297 TI - [Cytodiagnosis in the pathology of the extravisceral and non lymph node regions]. PMID- 3334298 TI - [Cytodiagnosis using fine needle aspiration in otorhinolaryngologic pathology]. PMID- 3334299 TI - [Cytodiagnosis of the salivary glands]. PMID- 3334300 TI - [Auditory evoked potentials of the encephalic trunk in patients with multiple sclerosis. A comparative analysis of the results obtained with various methods of tracing registration]. PMID- 3334301 TI - [Pharmacologic stimulation of surfactant at the pulmonary level]. PMID- 3334302 TI - [Ambroxol and stimulation of the pulmonary surfactant]. PMID- 3334303 TI - [Role of surfactant in the pathogenesis of secretory otitis media]. PMID- 3334304 TI - [Treatment of secretory otitis media with ambroxol]. PMID- 3334305 TI - [Tenso-active property of the eustachian tube mucosa]. PMID- 3334306 TI - Symposium Morpho Logica. April 8, 1986, Groningen. On the occasion of the retirement of Prof. A. G. de Wilde. PMID- 3334307 TI - A preliminary retrospective survey of herpes simplex disease presenting over 15 years. PMID- 3334308 TI - Factors of corneal endothelial proliferation. PMID- 3334309 TI - Lid reconstruction to correct trichiasis. PMID- 3334310 TI - [The intestinal ecosystem of mice after administration of a polyvalent oral vaccine]. AB - Bacterial antigens orally administered, have been showed by many Authors capable to stimulate immunity system, hinding thus the pathogen flora from gut colonization. Founding on these findings, AA. of the present paper intend to point out by collected microbial data and M.E.S. photos, the activity of an oral polyvalent vaccine made by lysates strains of E.coli, enterococci, staphylococci and P.vulgaris, on normal intestinal flora of mice contemporaneously administered with a pathogenic strain of Salmonella enteritidis. Vaccine showed himself to be able enough to limit alterations of intestinal flora due to infection by the pathogens. PMID- 3334311 TI - [Protection against experimental infections in mice by an oral vaccine and its combined role when administered with antibiotics]. AB - Immunomodulator with significantly modify the immunologic response of the host. The AA. studied the immunologic profile of an oral vaccine to protect the experimental infection in mice and its effect when it was administered with antibiotics. The mice infected with S. enteritidis were protected by the vaccine administered. Also in the group of mice treated with a vaccine and antibiotic combination, the mortality rate was lower than in the untreated groups. PMID- 3334312 TI - Rapid diagnosis by immunofluorescence of Chlamydia trachomatis cervical infections. AB - In this study the MicroTrak (Syva Co.) system has been evaluated in comparison with the isolation of Chlamydia trachomatis onto McCoy cell monolayer, testing 120 endocervical samples taken from an unselected women population. The overall results show a higher incidence of positivity in women under 30 years of age; a sensitivity of the immunofluorescence of 76.3% and a specificity of 89.8%. The agreement between the two methods is significative when we test symptomatic patients. PMID- 3334313 TI - [Materno-fetal colonization by group B beta-hemolytic streptococcus and neonatal meningitis]. AB - Two cases of purulent meningitis by Group B streptococci are reported. The bacteria agents were clearly transmitted transplacentally from mother to child. The bacteriological and clinical data are reported and discussed in relation to international literature. PMID- 3334314 TI - [Vaginal microbial flora and infectious pathology]. AB - Qualitative and quantitative studies in humans as well as animal models studies have confirmed that the vaginal flora is a dynamic and interrelated system. Factors influencing and changing vaginal ecology are considered. The disturbances in the vaginal flora may have impact on many infectious affections. Moreover the review examines concisely the microbial agents of the sexually transmitted diseases. PMID- 3334315 TI - [The development of immunology in a century of research]. AB - Immunology started in 1880 with the observation of Pasteur upon attenuated strains of Pasteurella aviseptica and evolved in nearly one century until the actual situation. Havig discussed the immunology topics, this review ends by stressing some of the recent landmarks in immunology. PMID- 3334317 TI - Renal regulation of potassium metabolism. PMID- 3334316 TI - [Changes in surface characteristics of group A streptococci]. AB - We examined the surface characteristics of four group A Streptococcus strains in log or stationary phase of growth by using the techniques of salt aggregation and of adhesion to n-hexadecane. By means of the former technique a greater correlation was observed between surface hydrophobicity and production of M protein (above all in stationary phase of bacteria). Using the latter one, we noted differences depending on the growth phase, but not related to M protein. The pretreatment of bacteria with subCMI of clindamycin decreases their hydrophobicity, particularly in M+ strains and in stationary phase of growth. Less variations of surface were observed in M- strains and after treatment with subCMI of imipenem. PMID- 3334318 TI - Presidential address. Concepts and misconcepts in venous disease. PMID- 3334319 TI - The legacy of Hippocrates: Greek medicine in the library of the Medical Society of London. PMID- 3334320 TI - Accident surgery past & present--has it a future? PMID- 3334321 TI - The current status of liver transplantation. PMID- 3334322 TI - The future pattern of general practice. PMID- 3334323 TI - Consent and confidentiality. PMID- 3334324 TI - Annual oration on medical politics--the myths and realities. PMID- 3334325 TI - [Ultrasound N staging in head and neck neoplasms: is an "umbilicate" image a sign of benignity?]. PMID- 3334326 TI - [Computerized stabilometry: a complete study in the examination of patients with vertigo]. PMID- 3334327 TI - [Adenocarcinoma of the ethmoid]. PMID- 3334328 TI - HPRT gene organization and expression. PMID- 3334329 TI - [The value of Duplex sonography in the diagnosis of deep leg and pelvic vein thrombosis]. AB - 50 cases, in which phlebography was indicated by clinical symptoms of deep venous thrombosis, were examined by duplex-sonography. In comparison with the phlebographic findings, duplex-sonography was 100% sensitive in detecting thrombosis of the popliteal, femoral and iliac veins and 89% respectively 95% and 100% specific. A sonographic performance of the calf veins was only possible in 44%, the sensitivity in these cases was 92%, specificity 50%. Thus, the non invasive duplex-sonography is a very appropriate method to diagnose thrombosis of the popliteal region and proximal. For proving or excluding thrombosis of the calf veins phlebography remains necessary. PMID- 3334330 TI - [Digital subtraction angiography of the hand]. AB - The conventional angiography using a serial film changer is the gold standard in hand arteriography. Since Digital Subtraction Angiography (DSA) is available, this method may substitute the conventional technique because of several advantages. This paper offers practical advice on intraarterial DSA-techniques and indications for hand arteriography additionally. Furthermore, differential diagnosis of arteriographic findings and the validity of DSA is discussed. PMID- 3334331 TI - [Growth curves of abdominal aortic aneurysms]. AB - 79 patients with abdominal aortic aneurysms were repeatedly examined by ultrasound to gain information about growth rate and prognosis. 67 small asymptomatic abdominal aortic aneurysms showed an average growth rate of 0.22 cm per year. 12 big aneurysms had a growth rate of 0.59 cm per year. The individual plots were highly variable. Only 5% of the patients died of rupture of the aneurysms, while 15% died of heart failure, myocardial infarction or cerebrovascular accident. Thus, the prognosis of small asymptomatic abdominal aortic aneurysms is better than in the medical literature of older date. PMID- 3334332 TI - [A patient with cystic adventitia degeneration and entrapment syndrome of the popliteal artery]. AB - Adventitial cystic disease and entrapment syndromes of the popliteal artery are rare causes of ischemia in the lower leg in younger patients without cardiovascular risk factors. The 38-year-old male patient described in this case report showed both types of these rare abnormalities in the same vessel, both usually requiring surgical revision even in causing only few symptoms. PMID- 3334333 TI - [Diagnostic possibilities of abdominal Duplex sonography]. AB - Abdominal duplex-sonography is a new method of diagnosing noninvasively arterial and venous lesions of abdominal vessels. Depending on the experience of the investigator definite diagnoses can be made in some cases. Further technical improvements of ultrasound probes and signal processing may give valuable information about hemodynamics of abdominal vessels. Thus, duplex-sonography is a useful addition of clarifying physiology and pathology of abdominal blood flow. PMID- 3334334 TI - [Basic abdominal ultrasound diagnosis course]. PMID- 3334335 TI - [Basic abdominal ultrasound diagnosis course. Nomenclature and description of findings]. PMID- 3334336 TI - [Indications and value of sonography in medical diagnosis]. PMID- 3334337 TI - [Basic abdominal ultrasound diagnosis course. Liver--normal findings and diffuse liver diseases]. PMID- 3334338 TI - [Basic abdominal ultrasound diagnosis course. The gallbladder and bile ducts. I]. PMID- 3334339 TI - [Basic abdominal ultrasound diagnosis course. The gallbladder and bile ducts. II]. PMID- 3334340 TI - [Basic abdominal ultrasound diagnosis course. The pancreas]. PMID- 3334341 TI - [Sonographic kidney diagnosis. Normal kidneys, normal variants, anomalies, nephrolithiasis, hydronephrosis]. PMID- 3334342 TI - [Basic abdominal ultrasound diagnosis course. Physical and technical principles]. PMID- 3334343 TI - [Basic abdominal ultrasound diagnosis course. The normal spleen]. PMID- 3334344 TI - [Basic abdominal ultrasound diagnosis course. Retroperitoneal blood vessels]. PMID- 3334345 TI - Cell kinetics of multiple myeloma. PMID- 3334346 TI - Recent advances in the biology of plasma cell myeloma. PMID- 3334347 TI - Immunoenzymatic method for detection of terminal deoxynucleotidyl transferase by light and electron microscopy. AB - Methods for using rabbit polyclonal and mouse monoclonal antibodies to detect terminal deoxynucleotidyl transferase (TdT) in human leukemia lines were developed. Use of 1% paraformaldehyde in 0.1 M Na cacodylate buffer, pH 7.6, as a fixative provides a procedure that can be used for immunofluorescence, immunoalkaline phosphatase (APAAP), or horseradish peroxidase conjugate detection procedures in these cell lines. The peroxidase procedure can also be used for electron microscopy, clearly demonstrating nuclear localization of TdT in interphase nuclei of TdT-positive cells. PMID- 3334348 TI - Chronic myelomonocytic leukemia terminating as malignant histiocytosis. AB - A patient with a 3.5 year history of chronic myelomonocytic leukemia who transformed to malignant histiocytosis is reported. The terminal event was characterized by fever, hepatosplenomegaly, thrombocytopenia, and a leukemic blood picture. The pathogenesis of this terminal transformation and proposed future studies are discussed. PMID- 3334349 TI - A new dentin bonding system. PMID- 3334350 TI - Incorporation of a previous fixed restoration in a complete denture. PMID- 3334352 TI - A modified six-step additive waxing system for developing the anatomically correct restoration. PMID- 3334351 TI - A classification of resin-bonded bridges based on the evolutionary changes of the different technique types. PMID- 3334353 TI - Two-piece cast superstructure for mandibular osseointegrated bridgework. PMID- 3334354 TI - An immediate interim complete denture technique. PMID- 3334355 TI - Fabrication of a stable mandibular complete denture trial base. PMID- 3334356 TI - Support for the distal extension removable partial denture. PMID- 3334357 TI - A plastic shell technique for fabricating porcelain-fused-to-metal coping patterns. PMID- 3334358 TI - Cast occlusal surfaces for a complete denture prosthesis utilizing the Triad light-curing system. PMID- 3334359 TI - The relationship of metal volume and sprue design to porosity in nonprecious castings. PMID- 3334360 TI - The production of a fixed complete mandibular denture using osseointegrated implants as abutments. PMID- 3334361 TI - A topographical assessment of casting ring liners using scanning electron microscopy (SEM). PMID- 3334362 TI - Arousal induced by injection of triazolam into the dorsal raphe nucleus of rats. AB - In order to explore the possible sites at which benzodiazepines alter sleep, we have performed sleep studies following administration of 0.5 microgram of triazolam into the dorsal raphe nucleus of rats. Triazolam significantly increased sleep latency and decreased non-rapid eye movement (REM) sleep, with an effect greatest in the first 2 hours after injection. Total REM sleep time was not significantly affected, although there was a modest trend toward reduction in the first 2 hours. In contrast to the decreased sleep resulting from injection into the dorsal raphe nucleus, triazolam did not significantly alter sleep in animals in whom it was injected into surrounding areas. Similarly, the low dose employed in this study did not significantly affect sleep when injected into the lateral ventricle. These data are reminiscent of studies showing transient decreases in sleep following lesions of the dorsal raphe nucleus. PMID- 3334363 TI - Fibronectin, the generation of multiple polypeptides from a single gene. PMID- 3334364 TI - Splicing of yeast mitochondrial precursor RNAs. PMID- 3334365 TI - Structure and expression of the chicken crystallin genes. PMID- 3334366 TI - Structural arrangement and tissue-specific expression of the two murine alpha amylase loci Amy-1 and Amy-2. PMID- 3334367 TI - Molecular genetics of class I genes in the mammalian major histocompatibility complex. PMID- 3334369 TI - Relationship between the velocity of polymerization and adaptation to dentin cavity wall of light-cured composite. PMID- 3334368 TI - Momentary pretreatment by 35% HEMA solution combined with five marketed bonding agents. PMID- 3334370 TI - The marginal gap and bonding strength of glass ionomers. PMID- 3334371 TI - Bonding of succinoxy alkylene methacrylates to dental alloys. PMID- 3334372 TI - Chromatic studies of porcelain veneered crown. (Part 1). Application of wire explosion spraying technique. PMID- 3334373 TI - Effect of a silane coupling agent and ferric chloride on the bonding of porcelain, quartz and alumina with 4-META/MMA-TBB resin. PMID- 3334374 TI - Attractive forces of Sm-Co magnet systems for stud attachment. PMID- 3334375 TI - Bone and fibrous tissue ingrowth into the porous Zr-Ti implants. PMID- 3334376 TI - Toxicology and health impact of environmental exposure to boron. A review. AB - The presence of high concentrations of boron in community water supplies has been reported as a localized problem in certain areas of United States, USSR and Italy. In this paper, current information on sources, occurrence, pollution potential and toxicity of environmental boron is reviewed. In animals, chronic low-level boron exposure has been shown to cause reduced growth, cutaneous disorders and suppression of male reproductive system function. The mechanisms underlying these effects and available data on dose-response relationships are discussed in connection with human health hazards possibly associated with continuous low-level absorption of boron compounds. PMID- 3334377 TI - [Chronobiology and industrial medicine: approach to the evaluation of the toxicological risk in occupational exposure to xenobiotics]. AB - The recent interest of occupational medicine for chronobiology has been mainly devoted to the fields of energy expense and nutrition, work performance, social and work organization. However, experimental studies of chronotoxicology have showed that the effects of noxious agents vary according to biological time of exposure, nature of toxic agents, and target organ. This fact indicates that the different responses to xenobiotics depend on the temporal variation of susceptibility, which represents a characteristic of each living species. In some instances, the biological differences of susceptibility have been regarded as a consequence of the different capability of the organs to biotransform the xenobiotics itself. Another aspect of chronotoxicology seems to be of great interest for the occupational toxicology. In fact, the evaluation of the toxicological risk in work environment is based, in addition to the environmental monitoring, on the measure of indices both of exposure and effect. Recently, it has pointed out the importance of the knowledge of the temporal behaviour of these indices to avoid misinterpretations of the results. These considerations may lead to a new and wider approach to the evaluation of environmental risk. PMID- 3334378 TI - Human toxicology of boron with special reference to boric acid poisoning. AB - The improper use of boric acid containing antiseptics is still one of the most common causes of toxic accidents in newborns and infants. Health hazards may also arise from inadvertent absorption of insecticides and household products containing borates as well as from occupational accidents related to production and use of boranes. A variety of boronated agents with hypolipidemic, antiinflammatory or anticancer properties have been developed in recent years. Unfortunately, most of these compounds were found to be highly toxic when tested at the required therapeutic dosages in animals. In this paper, recent information on human toxicology of boron is reviewed, with special emphasis on epidemiological and clinical aspects of boric acid poisoning. PMID- 3334379 TI - Human obsolescence and rejuvenescence: some literary treatments. PMID- 3334380 TI - Cognitive processes in the elderly: general factors to consider. PMID- 3334381 TI - [Review on internal medicine (1986). Recent progress in hematology. 1. Oncogene]. PMID- 3334382 TI - [Review on internal medicine (1986). Recent progress in hematology. 2. Hematopoietic stem cells]. PMID- 3334383 TI - [Review on internal medicine (1986). Recent progress in hematology. Stem cells]. PMID- 3334384 TI - [Review on internal medicine (1986). Recent progress in hematology. Refractory anemia; its definition and clinical characteristics]. PMID- 3334385 TI - [Review on internal medicine (1986). Recent progress in hematology. 4. Secondary immunodeficiency]. PMID- 3334386 TI - [Review on internal medicine (1986). Recent progress in hematology. 6. Blood component transfusion and guidelines for clinical use]. PMID- 3334387 TI - [Review on internal medicine (1986). Recent progress in hematology. 7. DIC]. PMID- 3334388 TI - [Review on internal medicine (1986). Recent progress in hematology. 7. Local DIC- DIC accompanying aortic aneurysm]. PMID- 3334390 TI - [Review on internal medicine (1986). Recent progress in hematology. 9. Drug induced haematological disorders]. PMID- 3334389 TI - [Review on internal medicine (1986). Recent progress in hematology. 8. Evaluation of antiplatelet therapy on biochemical and pharmacological basis]. PMID- 3334391 TI - [Review on internal medicine (1986). Recent progress in hematology. Drug-induced blood dyscrasia]. PMID- 3334392 TI - [Primary amyloidosis with ankylosing of the spine as an initial symptom and a fatal outcome due to restriction of breathing motions]. PMID- 3334393 TI - [A fatal case of probable Tsutsugamushi disease in Saitama Prefecture, with particular reference to 8 fatal cases occurring in Japan from 1962 to 1985]. PMID- 3334394 TI - [Review on internal medicine (1986). Recent progress in hematology. 5. Bone marrow transplantation]. PMID- 3334395 TI - Monoclonal anti-idiotypic antibodies as surrogates for hepatitis B surface antigen. PMID- 3334396 TI - Anti-idiotypic antibodies as idiotope vaccines that induce immunity against infectious agents. PMID- 3334397 TI - Anti-idiotypic antibodies of reovirus as biochemical and immunological mimics. PMID- 3334398 TI - Vector salivation and parasite transmission. AB - Saliva of blood-sucking arthropods contains substances that counteract the host's hemostatic and inflammatory reactions, allowing the arthropod to locate blood and keep it flowing during the blood meal. Parasites may manipulate this system in order to achieve increased transmission, both to vertebrate and to invertebrate hosts. Additionally, salivary pharmacological substances may locally immunosupress the delivery site, allowing initial colonization of the vertebrate host by the parasite. PMID- 3334399 TI - Inputs to the hormonal control of egg development in Rhodnius prolixus. AB - This paper re-examines existing data on the environmental inputs governing egg production in Rhodnius prolixus. Feeding has a direct effect on egg production such that the product of the unfed weight of the female times the weight of the blood meal is a good predictor of the number of eggs produced. Mating modifies this input, so that mated females produce more eggs. Egg production is governed by the corpus allatum, and indirect evidence suggests that the number of eggs producted by a female is a function of the length of time that juvenile hormone is secreted by the corpus allatum. The input which determines the times at which the corpus allatum is switched off originates in the stretch induced by the amount of the meal remaining in the crop, modified by the matedness status of the female. The precise nature of the sensors detecting stretch is not yet clear, but the integrity of the dorsal aorta is essential to the transmission of the information. These data are related to the survival strategy for Rhodnius. PMID- 3334400 TI - The study of insect blood-feeding behaviour. 1: Feeding equipment, physical and endogenous factors, dose effect analysis, and diet destination. AB - Experimental techniques that we have found useful during our studies of insect blood-feeding behaviour are reviewed. Some of the principal findings resulting from these techniques are discussed. Where directly applicable, the work of others is included, but no complete review of the subject has been attempted. PMID- 3334401 TI - Insect immunity--a gene system for antibacterial proteins. PMID- 3334402 TI - Gene amplification in Rhynchosciara (1955-1987). AB - A review is made of the evidence indicating the existence of gene amplification in Rhynchosciara, from the early cytological work to the more recent studies using cloned sequences from the DNA puffs. Mention is made of work still in progress which indicates that the transcription unit of a DNA puff is surprisingly complex. PMID- 3334403 TI - Effects of precocene and azadirachtin in Rhodnius prolixus: some data on development and reproduction. AB - The results presented in this paper clearly indicate that precocene and azadirachtin are effective inhibitors of moulting and reproduction in the hemipteran Rhodnius prolixus. The time of application is important and only applications of these substances early in the intermoulting period cause their effects in nymphs. The inhibition of moulting is fully reversed by ecdysone therapy. Precocene and azadirachtin also affected drastically the oogenesis and egg deposition in this insect. Precocene-induced sterilization is reversed by application of juvenile hormone III. However, this hormone is unable to reverse the effect of azadirachtin on reproduction. Ecdysteroid titers in nymphs and adult females are decreased by these treatments. In vitro analysis suggest that precocene and azadirachtin may act directly on the prothoracic glands and ovaries producing ecdysteroids. Based on these and other findings the possible mode of action of these compounds on the development and reproduction of Rhodnius prolixus is discussed. PMID- 3334404 TI - Secretory activity and endocrine regulation of male accessory glands in the blood sucking bug Panstrongylus megistus (Hemiptera: Reduviidae). AB - The epithelial cells of Panstrongylus megistus male accessory glands (MAG) present ultrastructural characteristics of a secretory cell. Their secretory products are accumulated in the lumen of the four MAG lobes. During the first 8 days of adult life a strong secretion activity occurs, accumulating enough material to produce the first spermatophore. Cerebral neurosecretions as well as juvenile hormone are both involved in MAG secretory activity regulation. Juvenile hormone seems to be the responsible for the stimulation of most protein synthesis in male accessory glands. Cerebral neurosecretion seems to be necessary to stimulate juvenile hormone production and release by the corpus allatum. Furthermore, neurosecretion is required for some polypeptides synthesis by MAG. Although topic application of precocene II to adult males does not reproduce the same effects on MAG as does allatectomy, this compound causes strong reduction on male reproductive capacity. PMID- 3334405 TI - The roles of haemolymphatic lipoproteins in the oogenesis of Rhodnius prolixus. AB - The fates of purified 32P-vitellin and 32P-lipophorin were followed in vitellogenic females of Rhodnius prolixus. While the radioactivity from 32P vitellin 6 hours after injection was found almost exclusively in the ovary, the radioactivity from injected 32P-lipophorin was found distributed among several organs. In the ovary, the radioactivity from 32P-vitellin was associated with the contents of the yolk granules. 32P-lipophorin delivered a great amount of radioactive phospholipids to the ovary with no accumulation of its protein moiety, as observed after its iodination with 131I. The delivery of phospholipids was inhibited at 0 degrees C and by the metabolic inhibitors, sodium azide and sodium fluoride. Comparison of the radioactivity incorporation from 32P lipophorin with that of 14C-inulin suggests that the 32P-phospholipids from lipophorin are not taken up by fluid phase endocytosis. The data presented here are compatible with the concept of lipophorin as a carrier of lipids in insects and provide evidence that lipophorin transports phospholipids as shown previously for other classes of lipids. The utilization by the oocytes of the phospholipids transported by lipophorin is discussed. PMID- 3334406 TI - HCFA's plan for implementation of the Medicare second opinion program. PMID- 3334407 TI - Denial of payment for poor quality care. Missouri's PRO explains Medicare's latest requirement. PMID- 3334408 TI - Congenital dislocation of the hip. Detection and management. PMID- 3334409 TI - What a dictionary reveals about medicine. PMID- 3334411 TI - Kinetic-effect models and their applications. AB - This article focuses on mathematical models that analyze the time course of drug effects in humans. Any such model, whether parametric or nonparametric, is termed a kinetic-effect model (KEM). These models serve to describe (interpolation) and to predict (extrapolation) the effect-time profile. KEMs are applicable to many problems in pharmaceutics, pharmacology, and clinical pharmacology. PMID- 3334410 TI - Selection of a derivative of the antiviral agent 9-[(1,3-dihydroxy-2-propoxy) methyl]guanine (DHPG) with improved oral absorption. AB - Various diesters of 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) were screened in order to identify a derivative with improved oral absorption. The solubilities and dissolution rates decreased with increasing chain length and branching of the ester group. However, the dipropionate ester showed an anomalously faster dissolution rate. The rates of hydrolysis to DHPG in the presence of intestinal homogenates were found to increase with increasing carbon number for the straight-chain alkyl esters and decreased with branching. The shorter-chain alkyl esters were relatively more stable in intestinal homogenates than in liver homogenates. Therefore they may have a better membrane permeability than DHPG due to their intact ester group. The hydrolysis rates in human blood increased with increasing carbon number for the straight-chain alkyl esters. The dipropionate ester appeared to be the most promising derivative because of its rapid dissolution rate, slower hydrolysis in the intestine, and rapid conversion to DHPG in liver and blood. PMID- 3334413 TI - Kinetics and mechanism of captopril oxidation in aqueous solution under controlled oxygen partial pressure. AB - The stability of captopril in aqueous solution at 32 degrees C was studied in the pH range 6.6 to 8.0 under controlled oxygen partial pressure (90-760 mm Hg) with and without the addition of cupric ion. The oxidation product, captopril disulfide, was found to be the sole degradation product. A change in reaction rate from first order to zero order occurs as the captopril concentration decreases. The concentration at which this transition takes place is a function of the pH, oxygen partial pressure, and cupric ion concentration. The apparent first-order rate constants show a first-order dependency on both the oxygen partial pressure and the cupric ion concentration. However, the apparent zero order rate constants show a first-order dependency on oxygen partial pressure and a second-order dependency on cupric ion concentration. As the pH increases from 6.6 to 8.0, the first-order process becomes more predominant. A mechanism which consists of cupric ion- and molecular oxygen-catalyzed oxidation is proposed to explain those observations. PMID- 3334412 TI - Use of vaccinia virus to express biopharmaceutical products. AB - Recent technological advancements have fostered the continued development of vaccinia virus as an efficient eukaryotic cloning and expression vector system. Genetically engineered vaccinia virus strains have been constructed for use (i) as recombinant vaccines for the prophylaxis of infectious disease, (ii) in producing significant quantities of biologically active polypeptide factors or enzymes, and (iii) as basic research tools with which to investigate primary structure-function relationships between proteins and their catalytic activities. This review examines the basic vaccinia vector system, its advantages and limitations, and current areas of research. As a specific example of the power and utility of this approach, attention is focused on the application of this technology to the field of neurobiology, specifically the use of recombinant vaccinia to study the expression, processing, and transport of cellular neuropeptides. PMID- 3334414 TI - Etiopathogenic mechanisms of bronchoconstriction in byssinois--a review. AB - Studies of etiopathogenic mechanisms of bronchoconstriction in byssinosis indicate the possible involvement of histamine, 5-HT, platelet-activating factor, and metabolites of arachidonic acid as mediators of bronchoconstriction. These substances might be released by a variety of lung and/or recruited cells to induce construction of respiratory airways characteristic of the acute byssinotic reaction. It certainly seems possible that cotton dust induces acute bronchoconstriction by more than one mechanism and that a number of factors, both endogenous and exogenous, influence the increased bronchomotor response to cotton dust inhalation in any given textile worker. PMID- 3334415 TI - Mechanisms of hypoxic pulmonary vasoconstriction. AB - During the last 4 decades hypoxic vasoconstriction has been acknowledged as an important pulmonary control mechanism that via matching ventilation and perfusion regulates one of the important physiologic parameters--PaO2. Whether the hypoxic vasoconstriction occurs directly in a localized vascular site with distinct biochemistry or whether it is mediated by a local hormone has not been resolved. Progress has been made because of the introduction of micropuncture techniques that allow direct pressure measurements in small segments of the lung vascular tree. Measurements of the force of contraction and membrane potential (118) and manipulation of the environment of pulmonary microvessels are the most recent progress in the elucidation of the mechanism of hypoxic vasoconstriction. Elements of energy, oxygen, and lipid metabolism appear to contribute to the biochemistry of this elusive response. PMID- 3334416 TI - Regulation of antibody production in vitro by granulocyte-macrophage colony stimulating factor. AB - The precise molecular characteristics and the mode of action of the T cell derived lymphokines which augment antibody production in vitro remain uncertain. The use of ill-defined culture supernatants to dissect the cellular interactions in vitro involved in antibody production can lead to ambiguous results as the factors may act either on a contaminating non-B-lymphoid population or directly on the B lymphocyte. We report herein the development of a system for measuring in vitro primary antibody responses by murine spleen cells in which endogenous lymphokine production has been minimized by the in vivo administration of cytotoxic antibodies to deplete T lymphocytes and the addition of the glucocorticosteroid, dexamethasone, throughout the culture period. Using such an assay, a lymphokine activity was detected which was capable of augmenting the plaque forming cell response. This lymphokine was present in culture supernatant derived from the lectin activation of the T cell lymphoma, LBRM-33 and was distinct from other known B cell activators, notably IL-2 and IFN gamma. Biochemical purification of this activity indicated that it might be identical to granulocyte-macrophage colony stimulating factor (GM-CSF). The use of recombinant derived GM-CSF protein unambiguously showed the role of this lymphokine in antibody production. These experiments demonstrated for the first time, the involvement of a hematopoietic factor in antigen-specific immune responses. Moreover, these results demonstrated an important regulatory circuit in the generation of antibody producing B cells in which GM-CSF, derived from activated T cells, stimulates macrophage function. PMID- 3334417 TI - [Isolation of prostacyclin from the vascular wall in an experiment]. PMID- 3334418 TI - [Symposium on diagnosis and treatment of cancer. Recent progress. I. Diagnosis. 1. Tumor marker. (1) Main topics on tumor markers]. PMID- 3334420 TI - [Symposium on diagnosis and treatment of cancer. Recent progress. I. Diagnosis 2. Imaging diagnosis. (1) Ultrasonography and computed tomography]. PMID- 3334419 TI - [Symposium on diagnosis and treatment of cancer. Recent progress. I. Diagnosis 1. Tumor marker. (2) Tumor-associated carbohydrate antigens]. PMID- 3334422 TI - [Symposium on diagnosis and treatment of cancer. Recent progress. II. Treatment of cancer 1. Recent cancer chemotherapy]. PMID- 3334421 TI - [Symposium on diagnosis and treatment of cancer. Recent progress. I. Diagnosis 2. Imaging diagnosis (2) Nuclear magnetic resonance (NMR)]. PMID- 3334423 TI - [Symposium on diagnosis and treatment of cancer. Recent progress. II. Treatment of cancer 2. Recent advance in immunotherapy]. PMID- 3334424 TI - [Symposium on diagnosis and treatment of cancer. Recent progress. II. Treatment of cancer 3. Hyperthermia]. PMID- 3334425 TI - [A case of Aeromonas hydrophila sepsis with generalized gas-formation and intravascular hemolysis]. PMID- 3334426 TI - [A case of oral pemphigus vulgaris involving the esophagus combined with early gastric carcinoma]. PMID- 3334427 TI - Control of schistosomiasis by use of biological control of snail hosts with special reference to competition. PMID- 3334428 TI - Pathology of human schistosomiasis. PMID- 3334430 TI - Localization of Schistosoma mansoni protective antigens by indirect immunofluorescence. PMID- 3334429 TI - A holistic view of schistosomiasis and snail control. PMID- 3334431 TI - Schistosomiasis: past, present and future. PMID- 3334432 TI - Sites and mechanisms of schistosome elimination. PMID- 3334433 TI - Cell-matrix interactions in schistosomal portal fibrosis: a dynamic event. AB - In recent years, one of the most significant progress in the understanding of liver diseases was the demonstration that liver fibrosis is a dynamic process resulting from a balance between synthesis and degradation of several matrix components, collagen in particular. Thus, fibrosis has been found to be a very early event during liver diseases, be it of toxic, viral or parasitic origin, and to be spontaneously reversible, either partially or totally. In liver fibrosis cell matrix interactions are dependent on the existence of the many factors (sometimes acting in combination) which produce the same events at the cellular and molecular levels. These events are: (i) the recruitment of fiber-producing cells, (ii) their proliferation, (iii) the secretion of matrix constituents of the extracellular matrix, and (iv) the remodeling and degradation of the newly formed matrix. All these events represent, at least in principle, a target for a therapeutic intervention aimed at influencing the experimentally induced hepatic fibrosis. In this context, hepatosplenic schistosomiasis is of particular interest, being an immune cell-mediated granulomatous disease and a model of liver fibrosis allowing extensive studies in human and animals as well as providing original in vitro models. PMID- 3334434 TI - [Agenesis of the lateral superior incisors: what treatment?]. PMID- 3334435 TI - [The shape of the dental arch]. PMID- 3334436 TI - Gene therapy. AB - Severe genetic disorders are potentially correctable by the addition of a normal gene into tissues. Although the technical problems involving integration, stable expression, and insertional damage to the treated cell are not yet fully solved, enough scientific progress has already been made to consider somatic cell gene therapy acceptable from both the ethical and scientific viewpoints. The resolutions to problems evolving from somatic cell gene therapy will help to overcome the technical difficulties encountered presently with germ line gene manipulation. This procedure would then become morally permissible as it will cause, in time, a reduction in the pool of abnormal genes in the population. Enhancement genetic engineering is technically feasible but morally unacceptable. Eugenic genetic engineering is not technically possible or ethically permissible in the foreseeable future. PMID- 3334437 TI - [Contemporary application of the active plate in the treatment of malocclusions]. PMID- 3334438 TI - [Alveolar soft part sarcoma--review of literature and report of a case]. PMID- 3334439 TI - [Dentin bonding agents]. PMID- 3334440 TI - [Progress in surgical treatment of aneurysm of the thoracic aorta]. PMID- 3334442 TI - [Magnesium metabolism]. PMID- 3334441 TI - [Changes in surgical treatment of coronary disease]. PMID- 3334443 TI - [Selection of bedside tests. Ultrasonic diagnosis]. PMID- 3334444 TI - [Selection of bedside tests. Pathology and cytodiagnosis]. PMID- 3334445 TI - [Interactions between subunits of the erythrocyte spectrin molecule--heat dissociation of the spectrin molecule]. PMID- 3334446 TI - [Band 3 protein: structure specificity of the cytoplasmic domain according to oligomer structure and species]. PMID- 3334447 TI - [Control of lateral mobility of band 3 by the cytoskeleton]. PMID- 3334448 TI - [Transport of inorganic phosphoric acid and phosphoenolpyruvic acid through the erythrocyte membrane: protein chemistry of the transport activities]. PMID- 3334449 TI - [Glycophorin and membrane surface proteins]. PMID- 3334450 TI - [Glucose transporter: expression of its function in erythrocytes and other cells]. PMID- 3334451 TI - [Function of the structure maintaining the morphology and elasticity of the erythrocyte]. PMID- 3334452 TI - A critical appraisal of drug stability testing methods. AB - The determination of potency or shelf life, impurity limit testing, and study of reaction mechanisms are considered as different aspects of drug stability. These aspects traditionally have been treated in isolation. The current criterion for a stability-indicating assay is criticized and the merits of choosing reactant or decomposition product for monitoring decomposition are discussed. The initial rate method of determining reaction order and rate constants by analysis of decomposition product is described and its potential advantages over traditional integral methods are discussed. Examples of the application of the initial-rate method to simple and complex drug decomposition systems for the determination of decomposition rate constants are given. Applications to limit testing and study of reaction mechanisms are outlined and the dependence of the initial-rate method and decomposition product analysis on modern chromatographic methods is emphasized. PMID- 3334455 TI - [Medical ethics in history]. PMID- 3334454 TI - Radioreceptor assay for insulin formulations. AB - A sensitive radioreceptor assay was developed for pharmaceutical insulin formulations with the use of rat liver membranes and 125I-insulin. The addition of unlabeled insulin or insulin analogues inhibited the binding of 125I-insulin to the receptors in a concentration-dependent way. Insulin concentrations between 3 x 10(-9) and 3 x 10(-8) M were used for a three-point assay which fulfilled pharmacopoeial statistical requirements for validity of the assay. The coefficient of variation for five assays was 4%. Potency estimates of insulin preparations obtained with the radioreceptor assay correlated well with corresponding estimates from in vivo assays. Both assays also gave similar potency readings for insulin preparations that were partly degraded during storage at elevated temperatures, but the radioreceptor method was more precise. PMID- 3334456 TI - [Human rights of psychiatric patients]. PMID- 3334453 TI - Immunoconjugates: applications in targeted drug delivery for cancer therapy. AB - Monoclonal antibodies can be produced against virtually any molecule, and unlike polyclonal antisera, they are highly specific. There has been great improvement in the monoclonal antibody production technique since its inception in 1975. The idea behind using monoclonals to direct cancer treatments is based on the fact that surfaces of tumor contain a wide variety of proteins, some of which are specific to the tumor type. Monoclonal antibodies that bind to such tumor specific antigens could be used, either alone or as conjugates of drugs and toxins (immunoconjugates), to selectively seek out and destroy these tumor cells. Targeted drug delivery therapy of tumor using monoclonals or their conjugates has been reported by many investigators, and the early results are quite promising. However, many obstacles still have to be overcome before immunoconjugates become a valuable agent in the treatment of human diseases including cancer. PMID- 3334458 TI - [Gene transfer into plant cells by electric field pulse]. PMID- 3334457 TI - [Synchronization of suspension culture]. PMID- 3334459 TI - [Induction of differentiation in plant cell culture systems]. PMID- 3334460 TI - [Protoplasts isolated from microsporocytes and microspores in higher plants]. PMID- 3334461 TI - [Staining and measurement of ultra small amount of DNA by fluorescence microscopy]. PMID- 3334462 TI - [Nuclei and chromosomes]. PMID- 3334463 TI - [Protein A-gold technique]. PMID- 3334464 TI - [Fractionation of organelle membranes]. PMID- 3334465 TI - [Analysis of plant membrane lipids]. PMID- 3334467 TI - [Introduction and expression of foreign genes into plant cells using a Ti plasmid vector]. PMID- 3334468 TI - [Purification of mRNA by polysome immunoprecipitation]. PMID- 3334466 TI - [Preparation of monoclonal antibody and its application for plant cell biochemistry]. PMID- 3334470 TI - [Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO)]. PMID- 3334469 TI - [Cell cycle-dependent regulation of transcription of plant genes]. PMID- 3334471 TI - [Gene for a rice storage protein glutelin]. PMID- 3334472 TI - [Structure and expression of genes coding for sporamin, the major protein of the sweet potato tuberous root]. PMID- 3334473 TI - [Multigene families in plants]. PMID- 3334474 TI - [Mitochondria (plant leaves)]. PMID- 3334476 TI - [Chloroplast proteins]. PMID- 3334475 TI - [Chloroplast DNA]. PMID- 3334477 TI - [Lipid synthesis in the chloroplast]. PMID- 3334478 TI - [Amyloplast DNA]. PMID- 3334479 TI - [Mitochondrial DNA]. PMID- 3334480 TI - [Mitochondrial proteins]. PMID- 3334481 TI - [Microbodies]. PMID- 3334482 TI - [Microbody transition in higher plants]. PMID- 3334483 TI - [Biosynthesis of secretory enzyme]. PMID- 3334484 TI - [Dynamics of vacuolar compartment]. PMID- 3334485 TI - [Biogenesis of protein body]. PMID- 3334486 TI - [Osmoregulation in plant cells]. PMID- 3334487 TI - [Golgi body]. PMID- 3334488 TI - [Isolation of plant plasma membranes by an aqueous two-polymer phase system]. PMID- 3334489 TI - [Vacuoles]. PMID- 3334490 TI - [Protein body]. PMID- 3334491 TI - [Endoplasmic reticulum]. PMID- 3334492 TI - [Plant organelles]. PMID- 3334493 TI - [Biochemical aspect of microtubule protein from higher plants]. PMID- 3334494 TI - [X-ray structure analysis of blood pigments]. PMID- 3334495 TI - [Module structure of hemoglobin]. PMID- 3334496 TI - [The molecular genetics of human hemoglobin]. PMID- 3334497 TI - [Invertebrate hemoglobin]. PMID- 3334498 TI - [Molecular evolution of hemoglobin: on vertebrate hemoglobins, with special reference to primate and Insectivora hemoglobins]. PMID- 3334499 TI - [Cooperative effects in hemoglobin]. PMID- 3334500 TI - [Interaction of hemoglobin with red cell membrane]. PMID- 3334501 TI - [Hemoglobin in the red cell: cooperative interactions between red cell metabolism and hemoglobin]. PMID- 3334502 TI - [Cooperative effect in metal-substituted hybrid hemoglobins]. PMID- 3334503 TI - [NMR study of cooperativity in hemoglobin]. PMID- 3334504 TI - [Raman and infrared analysis of cooperativity in hemoglobin]. PMID- 3334505 TI - [CD analysis of cooperativity in hemoglobin]. PMID- 3334506 TI - [Present status of the hemoglobinopathy study in Japan and the world]. PMID- 3334508 TI - [Hemoglobin S (Hb S)]. PMID- 3334507 TI - [Site-directed mutagenesis studies of human haemoglobin]. PMID- 3334509 TI - [Unstable hemoglobins]. PMID- 3334510 TI - [Structure and function relationship of abnormal hemoglobins with disturbed oxygen binding functions]. PMID- 3334511 TI - [Hemoglobin M]. PMID- 3334512 TI - [Thalassemia syndromes: molecular and clinical aspects]. PMID- 3334513 TI - [Anemias]. PMID- 3334514 TI - [Glycated hemoglobin]. PMID- 3334515 TI - [Determination of the primary structure of hemoglobin with special reference to the identification of abnormal hemoglobins]. PMID- 3334516 TI - [Structural analysis of hemoglobin variants by mass spectrometry]. PMID- 3334517 TI - [Electronic structure of the binding of O2, CO and NO with heme iron]. PMID- 3334518 TI - [Computational chemistry for heme and electrons]. PMID- 3334519 TI - [Structure and function of hemoglobin analogues]. PMID- 3334522 TI - [Tryptophan 2,3-dioxygenases and their reaction mechanisms]. PMID- 3334520 TI - [Stability properties of oxymyoglobins]. PMID- 3334521 TI - [Functions and structures of cytochromes P-450]. PMID- 3334523 TI - [Peroxidase]. PMID- 3334525 TI - [Hemerythrin]. PMID- 3334526 TI - [Picket-fence iron and cobalt porphyrins]. PMID- 3334524 TI - [Hemocyanin]. PMID- 3334527 TI - [Reconstituted myoglobins and hemoglobins with synthetic hemes]. PMID- 3334528 TI - [Heme biosynthesis and its regulation]. PMID- 3334529 TI - [Porphyria]. PMID- 3334531 TI - [Bilirubin]. PMID- 3334530 TI - [Heme degradation by heme oxygenase system]. PMID- 3334532 TI - [Mechanism of oxidation and reduction of hemoglobin]. PMID- 3334533 TI - [Methemoglobin reducing systems]. PMID- 3334534 TI - [Cytochrome b5 and methemoglobin reduction]. PMID- 3334535 TI - [Hereditary methemoglobinemia]. PMID- 3334536 TI - Rationale for non-surgical periodontal treatment. PMID- 3334537 TI - Periodontal considerations in restorative dentistry. PMID- 3334538 TI - Composite restorative materials: a review. PMID- 3334539 TI - Selection of elastomeric impression materials for crown and bridgework. PMID- 3334540 TI - In vitro effect of citric acid on planed diseased root surfaces. PMID- 3334541 TI - Clavulanic acid, a novel beta-lactamase inhibitor--a case study in drug discovery and development. AB - The research programme leading to the discovery of clavulanic acid and the olivanic acids (carbapenems) is reviewed. The beta-lactamase inhibitory properties of clavulanic acid and its development as a formulation with amoxycillin (Augmentina) and ticarcillin (Timentin) are described. The chemistry of clavulanic acid as well as the properties of the carbapenem family of antibiotics is outlined as are the other beta-lactamase inhibitors prompted by the development of clavulanic acid. PMID- 3334542 TI - Concerning steric effects in antimalarial agents. AB - Acridine, the parent nucleus of atabrine, is much more toxic than its 4,5 dimethyl derivative. The 4,5-dimethyl derivative of atabrine was therefore synthesized in the hope of producing a better-tolerated drug. The analogue was considerably more toxic than atabrine. PMID- 3334543 TI - Current innovations in drug delivery. AB - It is almost twenty years since the attention of the pharmaceutical industry was focussed on an alternative strategy--improving existing medicines by better control of the site, duration and intensity of the drugs they contain. Whilst site specificity remains a major objective for future medicines, progress has mainly come from devices which modulate the duration and intensity of drug action. In their most advanced form, they will deliver their contents in response to a physiological or pathological demand such as a diabetic's glucose level. However, practical devices have been limited to passive dosage forms which either speed up or slow down the rate of systemic absorption in a controlled manner. Oral, rectal, percutaneous and parenteral routes have been energetically explored and several products have been successfully marketed. Oral administration has dominated invention. Future advances will embrace the concepts of variable or pulsed release in order to meet particular therapeutic criteria. Equally important will be the extension of transit time in order to increase the uptake of some poorly absorbed drugs, or to extend dosage intervals to twenty-four hours. Attempts to more closely approach constant release rates at the end of the release period, to devise efficient formulae which carry drug loadings in excess of eighty per cent, or to invent formulae which, whilst retaining precision, are cheaper and more easily manufactured are less innovative aspects of this important field. The commercial success of percutaneous presentation of glyceryl trinitrate has prompted further refinement of this principle and guidelines for exploitation are now clearer. The development of acceptable penetration enhancers remains an important element in extending this principle to a wide range of drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3334544 TI - Comparative determination of phenytoin in plasma by fluorescence polarization immunoassay and high performance liquid chromatography. AB - The need for careful monitoring of plasma concentrations of phenytoin during use of the drug in the treatment of epilepsy is well recognized; there can be great intersubject variation in the absorption rate and clearance rate of the drug, and its therapeutic ratio is narrow. In this study, two methods for determining plasma phenytoin concentrations were compared. One, based on fluorescence polarisation immunoassay (FPIA), is utilised in a commercially-available kit. The other, our own modification of a published procedure, was based on high performance liquid chromatography (HPLC). The accuracy and precision of both methods were evaluated, and the coefficients of variation (C.V.) were calculated. The C.V.'s ranged from 0.71 to 1.86% for the FPIA method, and from 2.81 to 8.69% for the HPLC method. Corresponding bias values were 1.20 to 1.60%, and 2.81 to 8.69%, respectively. A good correlation coefficient (0.977) was obtained, but estimated phenytoin concentrations were significantly higher (95% confidence level) using the HPLC method. We conclude that both methods perform adequately for clinical purposes. The HPLC method is, however, less expensive than the FPIA method. PMID- 3334545 TI - Mechanism based design of inhibitors of neuropeptide degrading enzymes. PMID- 3334546 TI - Exploration of a chemical series as a drug discovery strategy. AB - Thought process common to many medicinal chemists are exposed in this example dealing with the quest for the discovery of new analgesic agents. The unexpected course of a chemical reaction, and subsequent random screening of the product, led to the serendipidous finding of CNS activity in the phenylcyclohexylamine derivative (9). In the development of the lead, synthetic targets were continually adjusted as the result of subsequent biological testing, and finally produced two compounds (34 and 35) with clinical potential as analgetics. Each failed to enter clinical testing due to their toxicity, but the overall results led to new concepts of the nature of the mu opioid receptor. PMID- 3334548 TI - Update on cholinergic enhancement therapy for Alzheimer disease. AB - Although patients with Alzheimer disease have a well-demonstrated deficit in cortical cholinergic markers, treatments designed to enhance cholinergic activity in the central nervous system have not achieved the clinical success of dopamine replacement for Parkinson disease. A brief review of recent clinical reports and some developments in the neurosciences suggests that it may be premature, however, to abandon the search for benefit from cholinergic enhancement therapy in Alzheimer disease. PMID- 3334547 TI - Combination effect of penetration enhancers and propylene glycol on in vitro transdermal absorption of insulin. AB - In vitro transdermal absorption of insulin was improved when the penetration enhancers Azone, N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO) were incorporated in propylene glycol (PG) formulations of the drug. Maximum penetration efficacy depended on optimal concentrations of both the enhancer and PG. Azone and NMP showed maximum efficacy at 0.1% and 12.0% concentration, respectively. In both cases, the optimum concentration of PG was 40.0%. The enhancing ability of DMSO was much lower in comparison with the other two enhancers. PMID- 3334550 TI - Aztreonam's influence on the Salmonella typhimurium relationship with Balb/c and CBA mouse Kupffer cells. PMID- 3334549 TI - Language disorders: clinical classification and neurovascular substrate. AB - The most prevalent cause of focal brain disease is stroke, Neuroanatomic localization in aphasia--and by inference, the identification of brain regions associated with language functions--is largely determined by, and confounded with, left cerebral hemisphere vascular territories. Traditional nosology of the aphasias, alexias, and agraphias is not always logically coherent and ignores major neurolinguistic boundries, yet it retains the clinical utility of permitting reliable and valid anatomic inferences concerning the underlying neuropathologic substrate. PMID- 3334552 TI - In vitro activity of ciprofloxacin in comparison with aztreonam, imipenem, and ceftazidime against multiply resistant strains. PMID- 3334551 TI - Comparative in vitro activity of carumonam with gentamicin and other beta-lactam antimicrobials: a multicentric study. PMID- 3334553 TI - Further studies on the relative contributions of chemotherapeutic and immunostimulant activity of amphotericin B to its efficacy as an antifungal agent. PMID- 3334554 TI - Antibiotic synergism and antagonism: significance in clinical infections. PMID- 3334555 TI - Pathogenic factors in group B streptococci types IV and V. PMID- 3334557 TI - Statistical study of intrinsic resistance in Escherichia coli. PMID- 3334556 TI - Nature of transferable antibiotic resistance in Salmonella wien isolated in Egypt. PMID- 3334558 TI - Expression of resistance to quinolone antimicrobials. PMID- 3334559 TI - In vivo effect of ciprofloxacin on plasmid-mediated resistance. PMID- 3334560 TI - Influence of perioperative prophylaxis with mezlocillin on cellular immune response. PMID- 3334561 TI - Immunomodulating properties of newer cephalosporins: a preliminary classification. PMID- 3334562 TI - Fluoroquinolone derivatives: effects on neutrophil functional tests. PMID- 3334564 TI - Interaction of cefotaxime versus desacetyl cefotaxime on human neutrophil functions. PMID- 3334563 TI - Effect of ceftriaxone on bacterial killing by human neutrophils in vitro. PMID- 3334565 TI - Alterations of pharmacokinetic characteristics of antibiotics during sepsis: experimental and clinical data. PMID- 3334566 TI - Ceftazidime levels in bile and gallbladder tissue in patients undergoing cholecystectomy. PMID- 3334567 TI - Treatment of pyelonephritis with aztreonam: kinetic study in children. PMID- 3334568 TI - Penetration of ciprofloxacin and ofloxacin into pancreatic juice. PMID- 3334569 TI - Pharmacokinetic studies in rats with ofloxacin and MF-934, a new fluorinated quinolone. PMID- 3334570 TI - Susceptibility of Salmonella to eighteen antimicrobials: implications for treatment of Salmonella septicemia and meningitis. PMID- 3334571 TI - Safety profile of cefotetan--a summary of possible adverse reactions. PMID- 3334572 TI - Effects of cephalosporins and carumonam on blood coagulation. PMID- 3334573 TI - Leishmaniases: new research findings and their implications in therapy and control. PMID- 3334574 TI - Alternate treatment of Ancylostoma duodenale and Ascaris lumbricoides with albendazole and levamisole. PMID- 3334575 TI - Comparative study of two regimens in the treatment of brucellosis. PMID- 3334577 TI - Comparison of cefotetan versus cefoxitin for acute bacterial infections. PMID- 3334576 TI - Cefotaxime (C) vs cefotaxime + amikacin (C + A) in the treatment of septicemia due to enterobacteria: a multicenter study. PMID- 3334579 TI - Ceftazidime: therapeutic results in various infections. PMID- 3334578 TI - A controlled study of cefotetan versus cefotaxime in the treatment of acute infections. PMID- 3334580 TI - Clinical experience with ceftazidime in the management of a variety of gram negative infections. PMID- 3334581 TI - Efficacy and safety of azlocillin and ticarcillin in febrile neutropenic children with cancer: a comparative study. PMID- 3334582 TI - Role of antimicrobial combinations in the therapy of infections in neutropenic patients. PMID- 3334583 TI - Zoega medical papyrus. PMID- 3334584 TI - Aztreonam plus cefazolin: a double beta-lactam combination as empirical therapy in febrile cancer patients with or without granulocytopenia. PMID- 3334585 TI - European experience of timentin in combination with aminoglycosides as empirical treatment in febrile neutropenic patients. PMID- 3334586 TI - Ciprofloxacin: initial evaluation in immunocompromised patients. PMID- 3334587 TI - Josamycin versus erythromycin in the treatment of streptococcal pharyngitis in children. PMID- 3334588 TI - A comparative study with ceftriaxone (Rocephin) versus ampicillin and chloramphenicol in children with bacterial meningitis. PMID- 3334590 TI - Aztreonam in the treatment of gram-negative meningitis in children. PMID- 3334589 TI - Pharmacokinetics and clinical evaluation of ceftriaxone (CRO) in children with purulent meningitis. PMID- 3334591 TI - Ciprofloxacin versus cefotaxime in skin and skin structure infections: a double blind study. PMID- 3334592 TI - A prospective controlled study of cefotetan versus cefotaxime in the treatment of infections in trauma patients undergoing surgery. PMID- 3334593 TI - Detection of enterotoxigenic strains of Escherichia coli in children with acute diarrhea. PMID- 3334594 TI - Anaerobic infections of the head and neck. PMID- 3334595 TI - A review of anaerobic infections of the oral cavity in Egypt. PMID- 3334596 TI - Treatment of anaerobic infections in the upper respiratory tract. PMID- 3334598 TI - A double-blind comparison of spiramycin and doxycycline in treatment of respiratory tract infections (pneumonia and suppurative bronchitis). PMID- 3334597 TI - A randomized clinical trial comparing the safety and efficacy of cefonicid and cefamandole in the treatment of patients with respiratory tract infections caused by susceptible pathogens. PMID- 3334599 TI - Intra-abdominal infections: microbiological and clinical aspects. PMID- 3334600 TI - Controversies in intra-abdominal infections: microbiological and clinical aspects. PMID- 3334601 TI - Escherichia coli heat-labile enterotoxin: biological activity of crude filtrate and fractions isolated by gel chromatography. PMID- 3334602 TI - Treatment of intra-abdominal abscess in a patient with complicated Crohn's disease. PMID- 3334604 TI - Comparison of cefotetan versus combination therapy in peritonitis and serious intra-abdominal sepsis. PMID- 3334606 TI - A multicenter open clinical trial of cefotetan in the treatment of peritonitis. PMID- 3334603 TI - Treatment of intra-abdominal infections using imipenem/cilastatin. PMID- 3334605 TI - Monotherapy for bacterial peritonitis using cefotetan. PMID- 3334607 TI - Quinolones in the treatment of gastrointestinal infections. PMID- 3334608 TI - Ciprofloxacin versus placebo in the treatment of acute bacterial diarrhea. PMID- 3334609 TI - Infection versus rejection in renal transplantation. PMID- 3334610 TI - Netilmicin alone or in combination in renal transplantation. PMID- 3334612 TI - Carumonam and cefotiam in the treatment of complicated urinary tract infection (UTI): a randomized study. PMID- 3334611 TI - Piperacillin therapy for complicated urinary tract infections caused by enterococci alone and in association with multi-drug resistant pathogens. PMID- 3334613 TI - Carumonam versus ceftazidime: in vitro activity, pharmacokinetics in elderly patients, safety and therapeutic efficacy in the treatment of complicated urinary tract infections. PMID- 3334614 TI - Comparative study of Ro 17-2301 (AMA-1080) and amikacin in complicated urinary tract infections. PMID- 3334615 TI - A study of the use of norfloxacin in prostatitis. PMID- 3334616 TI - Low-dose norfloxacin versus placebo for long-term prophylaxis of recurrent uncomplicated urinary tract infection. PMID- 3334619 TI - Oxiconazole cream: a comparison of two treatment schedules. PMID- 3334617 TI - Piperacillin in prophylaxis and therapy of gynecologic cancer patients. PMID- 3334618 TI - A comparative study of cefotetan versus cefoxitin plus metronidazole in the treatment of gynecological infections. PMID- 3334620 TI - Comparative study of ceftriaxone and benzathine penicillin G in the treatment of primary and secondary syphilis. PMID- 3334621 TI - Chronic mucocutaneous candidiasis. PMID- 3334622 TI - Intraoperative microbiological sampling is unhelpful after prophylactic antibiotic. PMID- 3334624 TI - Antibiotic prophylaxis in neurosurgery. A clinical study. PMID- 3334623 TI - Antibiotic prophylaxis in surgery ranked by patients' risk rates. PMID- 3334626 TI - Perioperative antibiotic prophylaxis in mandibular fracture treatment. PMID- 3334625 TI - Perioperative prophylaxis in neurosurgery with ceftriaxone. PMID- 3334628 TI - Single-dose prophylaxis of ceftriaxone versus standard dosage of cefotaxime in the prophylaxis of bacterial complications in orthopedic surgery. PMID- 3334627 TI - Short-term antibiotic prophylaxis in elective oral and maxillofacial surgery with mezlocillin and oxacillin. PMID- 3334629 TI - Results of antibiotic prophylaxis in head and neck surgery. PMID- 3334630 TI - Short-term prophylaxis in thoracic surgery: what regimen? PMID- 3334631 TI - Influence of newer beta-lactams on normal human intestinal microflora. PMID- 3334632 TI - Systemic chemoprophylaxis in pacemaker surgery: a prospective randomized study. PMID- 3334633 TI - A comparison of cefuroxime and cefotetan in the prevention of wound sepsis after gastrointestinal surgery. PMID- 3334634 TI - Surgery prophylaxis with mezlocillin versus other beta-lactams. PMID- 3334636 TI - Mezlocillin and prophylaxis of postoperative infections in biliary surgery. PMID- 3334635 TI - Preventive preoperative chemotherapy with ceftriaxone or cefotaxime in abdominal surgery. PMID- 3334638 TI - Wound sepsis after colorectal surgery: the effect of cefotetan lavage. PMID- 3334637 TI - Comparison of cefotetan and gentamicin/ampicillin in high-risk biliary tract surgery. PMID- 3334639 TI - Single-shot antibiotic prophylaxis in colon surgery. PMID- 3334640 TI - History of antimicrobial chemotherapy: from Pasteur to penicillin. PMID- 3334641 TI - A prospective comparative study of cefotetan with piperacillin for prophylaxis against infection in elective colorectal surgery. PMID- 3334642 TI - Systemic versus systemic plus oral chemoprophylaxis in elective colorectal surgery. PMID- 3334643 TI - Perioperative infection prophylaxis in colon surgery. PMID- 3334644 TI - One versus three doses of metronidazole/mezlocillin for antibiotic prophylaxis in colon surgery. PMID- 3334645 TI - Antibiotic prophylaxis before extracorporeal shock wave lithotripsy by single shot application of azlocillin. PMID- 3334646 TI - Cefotetan vs. cefoxitin in short-term antibacterial prophylaxis in urological surgery. PMID- 3334647 TI - Evaluation of mezlocillin versus placebo as a prophylactic agent in cesarean section. PMID- 3334648 TI - Cesarean section: antibiotic prophylaxis with ceftezole. PMID- 3334649 TI - Abdominal hysterectomy prophylaxis with mezlocillin. PMID- 3334650 TI - Effectiveness of perioperative prophylaxis with ceftriaxone and cefotaxime in vaginal hysterectomy with and without anterior and/or posterior colporrhaphy. PMID- 3334651 TI - Antibiotic prophylaxis of infection after gynecologic surgery: a prospective randomized trial between cefotetan and piperacillin. PMID- 3334652 TI - Perioperative cefotetan one-shot prophylaxis in gynecologic/vaginal and abdominal surgery. PMID- 3334653 TI - HIV biology and pathways to AIDS prevention. PMID- 3334654 TI - Risk of HIV infection in recipients of blood and blood products. PMID- 3334655 TI - Beta-2-microglobulin serum levels in patients with HIV-infections. PMID- 3334656 TI - H2 receptor antagonists' influence on the clinical course of infectious mononucleosis. PMID- 3334657 TI - Evaluation immunogenicity of antirabies vaccines. PMID- 3334658 TI - Recent developments in the management of herpes zoster (shingles). PMID- 3334659 TI - Antitumor drugs. PMID- 3334661 TI - Leukemia and lymphoma. PMID- 3334660 TI - High-dose chemotherapy. PMID- 3334662 TI - Biological activity of ukrain in vitro and in vivo. PMID- 3334663 TI - Comparative in vitro activity of imipenem, the first thienamycin antibiotic: a review of a multi-center study. PMID- 3334665 TI - BCG-RIVM: a new BCG preparation for intravesical immunotherapy of superficial bladder cancer. PMID- 3334664 TI - Cytokinetic-based versus conventional chemotherapy in metastatic breast cancer: a randomized study. PMID- 3334666 TI - Susceptibility of enteric pathogens to amoxicillin and clavulanate-potentiated amoxicillin. PMID- 3334667 TI - Sensitivity to cefuroxime and ceftazidime of hospital strains isolated in Poland. PMID- 3334668 TI - Directory of food and nutrition institutions in the Near East. PMID- 3334669 TI - [Cavity cleansing agents: a review]. PMID- 3334670 TI - Dental education in a changing society. PMID- 3334671 TI - The stainless steel crown with a composite facing--a restoration for primary anterior teeth. PMID- 3334672 TI - Cystic ameloblastoma. PMID- 3334673 TI - Some observations on occlusal attrition from two medieval Irish sites. PMID- 3334675 TI - Extension of clips for subperiosteal implants. PMID- 3334674 TI - Apical surgery. An update. PMID- 3334676 TI - Presurgical implant systems design for optional prosthetic esthetics and function. PMID- 3334677 TI - Success and survivability of endosteal blade implants managed in the practice of Dr. Linkow. PMID- 3334678 TI - Photoplethysmography in the assessment of venous insufficiency. AB - Photoplethysmography has been used simultaneously with ambulatory venous pressure measurements to study 32 patients. Of the 62 limbs studied, 24 were normal, 20 had primary varicose veins, and 18 had deep valvular incompetence. The results indicate that the photoplethysmographic refilling time can provide a good separation between the three groups when the test is performed in the standing, but not in the sitting, position. However, the test is qualitative because we found a lack of correlation between the short refilling times in limbs with deep venous insufficiency and the ambulatory venous pressure. PMID- 3334679 TI - Successful aortic surgery after renal transplantation without protection of the transplanted kidney. AB - When renal transplant recipients undergo aortic surgery, blood supply to the renal graft is interrupted while the aorta is clamped. Several innovative ways of using shunts have been described to preserve blood flow to the transplanted kidney during such surgery on the assumption that temporary warm ischemia of the renal transplant is poorly tolerated. We have performed aortic surgery in four renal transplant recipients without the use of any form of graft protection. One patient underwent urgent operation to treat an expanding aortic aneurysm and the other three had elective surgery for aortoiliac occlusive disease. Ischemic times ranged from 30 to 45 minutes. Two of the four patients had a temporary rise in serum creatinine levels. No patient required hemodialysis. We conclude that in selected renal transplant recipients, aortic surgery can be safely undertaken without graft protection. PMID- 3334680 TI - Carotid body tumor: atypical angiogram of a functional tumor. AB - Carotid body tumors (CBTs) are rare, usually benign, neoplasms of the extra adrenal paraganglion system. They are almost always nonfunctional. The diagnosis is generally confirmed by an angiogram that shows a vascular tumor enlarging the space between the internal and external carotid arteries. A 55-year-old man with hypertension and episodes of flushing, palpitations, and dizziness was treated for a firm, nonmobile mass measuring 3 x 2 cm at the left carotid bifurcation. Plasma and urine catecholamines, and the vanilylmandelic acid/creatinine ratios were elevated. Carotid arteriograms showed a vascular mass displacing the vessels, but the space between the arteries was narrowed rather than enlarged, and an atherosclerotic plaque was present. At operation the CBT was removed by resection of the bifurcation and with a temporary shunt a saphenous vein graft was inserted between the common and internal carotid arteries. Pathologic examination revealed a typical paraganglionoma. Although most CBTs produce catecholamines, only 11 patients have been reported to have elevated plasma and urine levels, and most were symptomatic. Since these tumors slowly increase in size, early surgical removal is recommended, even in asymptomatic patients. PMID- 3334681 TI - Traumatic superior mesenteric arteriovenous fistula: report of a case and review of the literature. AB - Penetrating arterial injuries can result in the formation of a traumatic false aneurysm or an arteriovenous fistula. Traumatic arteriovenous fistulas of the mesenteric circulation are extremely rare, with only 15 operated cases reported in the English language literature that involved the superior mesenteric artery and vein. Although surgical intervention has been considered the most successful method to treat traumatic mesenteric arteriovenous fistulas, percutaneous transcatheter embolization has been occasionally advocated in the management of small iatrogenic fistulas. We report a case of a gunshot wound patient who had an 8 cm abdominal aortic false aneurysm, as well as a high-flow arteriovenous communication between the superior mesenteric artery and vein, which were successfully treated by a combination of aorto-superior mesenteric bypass and postoperative percutaneous transcatheter embolization. A review of the literature is also included. PMID- 3334682 TI - Pathophysiology of free radical-mediated reperfusion injury. PMID- 3334683 TI - Pathophysiology and prevention of acute renal failure associated with thoracoabdominal or abdominal aortic surgery. PMID- 3334684 TI - Protecting the brain and spinal cord. PMID- 3334685 TI - Nutrient bed protection during lower extremity arterial reconstruction. PMID- 3334686 TI - [The French Society of Orthodontics]. PMID- 3334687 TI - [Diagnosis and treatment in orthodontics: principles and decision diagrams]. PMID- 3334688 TI - [Functional structure of the human temporal-masseter muscle complex in the fetus and the adult]. PMID- 3334689 TI - [Georges Cuvier (1769-1832), his facial angle and the Hottentot Venus]. PMID- 3334690 TI - [The use of teleradiographic cephalometry in dentures]. PMID- 3334691 TI - [The development of indirect bonding in combination with pre-bonded appliances]. PMID- 3334692 TI - Antimicrobials and fish: a review of drugs used to treat bacterial diseases of channel catfish and rainbow trout. AB - The principal bacterial diseases of cultured rainbow trout (Salmo gairdneri) and channel catfish (Ictalurus punctatus), and the antibacterials used in their treatment are briefly reviewed. Gram-negative bacteria predominate, and oxytetracycline is effective in treatment of infections induced by them. The only antibacterials now registered by the US Food and Drug Administration are sulfamerazine for the treatment of furunculosis in trout, and oxytetracycline for the treatment of furunculosis in salmonids and Aeromonas and Pseudomonas infections in salmonids and catfish. Registration 9/50 is now complete for the potentiated sulfonamide Romet-30 for controlling furunculosis in salmonids. Studies on the metabolism of antibacterials in fishes are limited, and are primarily concerned with tissue residue and elimination rate. PMID- 3334693 TI - Metabolism, disposition, and toxicity of drugs and other xenobiotics in aquatic species. AB - An overview is given of the absorption, distribution, excretion, and in vivo metabolism of drugs in fish. Several methods for chemical disposition and metabolism in fish are outlined, and a few well-characterized studies of the relationships between xenobiotic metabolism and toxicity in aquatic species are highlighted. For more than 40 drugs and other xenobiotics in several species of fish, concentrations of chemicals in bile were usually considerably higher than values in other body compartments or in the surrounding water. This was shown to be true particularly for parent substances or their biotransformed products with molecular weights greater than 400. The use of bile analysis is recommended as a regulatory tool to detect contamination of fish from drug treatment or environmental exposure. PMID- 3334694 TI - mRNA-dependent yeast cell-free translation systems: theory and practice. PMID- 3334695 TI - Inter- and intra-species crosses between Candida albicans and Candida guilliermondii. AB - Hybridization was shown to occur both between strains of the imperfect diploid yeast Candida albicans and between C. albicans and the distantly related haploid yeast Candida (Pichia) guilliermondii. Prototrophic hybrids were selected from crosses of multiply marked auxotrophic mutants of the two species. In most cases, mild ultraviolet irradiation of the C. albicans partner was required. Examination of auxotrophic markers in segregants from the hybrids indicated that recombination, rather than heterokaryon formation, had occurred in these crosses. The DNA content of the hybrids varied from diploid or aneuploid (for crosses between C. albicans and C. guilliermondii) to triploid (for C. albicans x C. albicans). It seems possible that genetic exchange analogous to this may occur in nature. PMID- 3334696 TI - Identification of the RNA2 protein of Saccharomyces cerevisiae. AB - The rna2-1 mutant of Saccharomyces cerevisiae has a conditional lethal phenotype, accumulating high molecular weight RNAs of intron-containing nuclear genes at 36 degrees C. The cloned RNA2 gene suppresses this phenotype and the RNA2 gene product has been implicated in RNA splicing. Rabbit antisera have been raised against an N-terminal synthetic peptide taken from the RNA2 gene DNA sequence data, and against a beta-galactosidase/RNA2 gene fusion protein. Both antisera identify the same 97-105 kd protein from S. cerevisiae cell extracts which is consistent with the predicted size of the RNA2 protein (from the 2800 nucleotide transcript size and DNA sequence data). PMID- 3334697 TI - [Functional profile of the course stages of chronic bronchitis]. PMID- 3334698 TI - Chemotherapeutic trial of pulmonary sarcoidosis: a possible etiotropic treatment. PMID- 3334700 TI - Communication skills of young hearing-impaired children. PMID- 3334699 TI - [Current technics of biopsy of the mediastinum: 1) mediastinoscopy]. PMID- 3334701 TI - Inhibition of measles virus-induced cell-cell fusion with a monoclonal antibody directed against the haemagglutinin. AB - A neutralizing monoclonal antibody (C26-15) against the haemagglutinin (H protein) of measles virus was generated which caused cell-cell fusion inhibition in cultures of measles virus-infected cells. It was shown that this phenomenon coincided with a down-regulation of the expression of both the H protein and the fusion (F) protein. We also showed cell-cell fusion inhibition with a polyclonal rabbit serum directed against Tween-ether inactivated measles virus, which did not contain biologically active antibodies against the F protein. Cell-cell fusion inhibition caused by anti-H antibodies is distinct from cell-cell fusion inhibition induced by a direct interaction of anti-F antibody with the F protein in the membrane of infected cells. Since both mechanisms may also be involved in the in vivo situation, the exclusive role for the generation of anti-F antibody to prevent virus spread by cell-cell fusion in vivo is questioned. It is speculated that the observed down-regulation of both glycoproteins may lead to a less efficient killing of infected cells by cytotoxic T-lymphocytes, which may constitute an alternative explanation for the insufficient protection after vaccination with an inactivated measles vaccine. PMID- 3334702 TI - Shadow on the Land: the epidemiology of HIV infection. PMID- 3334703 TI - Immunological response to pre-S antigens of the hepatitis B virus. PMID- 3334704 TI - Expression and characterization of hepatitis B virus precore-core antigen in E. coli. AB - The hepatitis B virus core antigen, including the precore sequence (HBcAg-p25), was expressed at very high levels in bacteria. Three expression vectors were constructed in which the synthesis of HBcAg-p25 was controlled by the tac promoter, and the number of nucleotides between the bacterial ribosome binding site and the precore initiation codon was varied in order to maximize HBcAg-p25 synthesis. The relative amount of HBcAg-p25 polypeptide expressed by the different vectors was estimated by SDS-polyacrylamide gel electrophoresis and immunoblot. HBcAg-p25 was associated with an insoluble fraction of bacterial extracts and required ionic detergents for solubilization. Comparison by ELISA of the immunoreactivity of HBcAg with and without the precore sequence suggested that human anti-HBcAg IgG preferentially recognizes HBcAg lacking the precore sequence. PMID- 3334705 TI - Oxidative stress injury studied in isolated intact cells. AB - Oxidative damage produced by oxygen free radicals has been investigated in various mammalian cells in culture. Incubation of these cells with redox cycling quinones resulted in a stimulation of superoxide anion and hydrogen peroxide formation. Further metabolism of H2O2 by glutathione peroxidase caused oxidation and depletion of cellular glutathione followed by oxidation of protein sulfhydryl groups and cytotoxicity. Several targets susceptible to oxidative modification have been identified, including the mitochondrial, endoplasmic reticular, and plasma membrane Ca2+-translocases. As result, a marked and sustained increase in cytosolic free Ca2+ concentration occurred, followed by the activation of some catabolic Ca2+-dependent processes, namely phospholipases, proteases, and endonucleases. In addition, an impairment of the transmembranal signal transducing system(s) was found. Recent investigations demonstrated that several modifications occur also in the cytoskeleton of oxidative stress-challenged cells. They mainly consist of oxidative actin cross-linking and dissociation of the cytoskeleton from the plasma membrane. All these alterations appear to contribute to the multifactorial process underlying the irreversible cell injury caused by oxidative stress. PMID- 3334706 TI - Premenstrual syndrome: current assessment and management. PMID- 3334707 TI - Adaptation of the nursing audit to community health nursing. AB - A selected literature review has revealed some of the ways in which the audit can be adapted to effectively evaluate the quality of care provided by community health professionals. Although a complex issue, the strengths of the audit can outweigh its limitations when a shared philosophy is adhered to and a review of the quality monitoring process occurs on a regular basis. But its success depends both on the approach and on the action taken. One requirement for an effective audit is a strong commitment of staff to reflect accurately nursing practice in nursing documentation. As the audit is neither inclusive nor exclusive, it should be used in conjunction with other quality assurance mechanisms, and in collaboration with other disciplines. Commitment at all levels--consumer, provider, administrator--is essential for success. There is no doubt that the variety of nursing audit instruments and techniques in existence have served to enhance the effectiveness and efficiency of community health nursing audit programs as well as contributing to community health nursing quality assurance. However, the audit clearly remains a challenging issue, requiring further research to establish the reliability and validity of current audit measures and to develop innovative approaches to future community-based audits. PMID- 3334708 TI - Adult children of alcoholics: implications for the nursing profession. PMID- 3334709 TI - Postirradiation haemorrhagic syndrome. AB - One of the relevant symptoms of damage due to irradiation are the manifestations of haemorrhagic diathesis. The extravascular effusion of the blood in the course of the course of the irradiation disease may sometimes also be the cause of death of the irradiated individual, it may complicate the course of the arisen disease and sometimes even make any necessary therapeutical help impossible. The postirradiation disorder of haemocoagulation and haemostasis is a process very complicated both in its origin and in its course. Many experimental studies have been devoted to the study of the mechanism of origin of this disorder, of its course and of the possibilities of its therapy and actually we already have some clinical results. For a wider information and for the utilization of the up-to date findings in practise, we hold it reasonable to summarize, in a certain time period, the information, though of a restricted problem, in order to facilitate an orientation in the contributions research has made up to now and to enable the selection of the adequate direction of the future experimental studies. This was the reason for the compilation of this monograph in which a summary of the up-to date experience published in the literature and the results of our many-year standing experimental work is presented in the first opening chapter. In the second chapter, the mechanisms of blood clotting in man and the most often used laboratory animals in experiments, i.e. the dog, rabbit, rat and guinea pig, are compared. By a comparison of the platelet counts, of the time of their survival and the modes of reaction to the inductors of aggregation, some differences have been demonstrated between human thrombocytes and those of laboratory animals, which may be partly conditioned by some species specific composition of the glycoproteins of the platelet membrane. Further on, the difficulties in the determination of the levels of the individual coagulation factors are referred to and their values established in man are compared with those found in the examined laboratory animals in which decreased levels of factor VII and markedly elevated levels of factors V and VIII have been demonstrated. Next, the physiological inhibitors of blood clotting in man are compared with similar substances found in the blood of laboratory animals. Some differences in the structure and in the function of these substances slowing down the blood coagulation are stressed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3334710 TI - Contemporary issues in cardiovascular pathology. PMID- 3334711 TI - Heme proteins. PMID- 3334712 TI - Immunocytochemical evidence suggesting heterogeneity in the population of sea urchin egg cortical granules. AB - Unfertilized eggs of many species of animals contain cortical granules, which are specialized secretory granules that upon fertilization release their contents from the egg. The unfertilized eggs of the sea urchin, Strongylocentrotus purpuratus, contain cortical granules that all display an identical and elaborate internal morphology. It has been assumed that they all contain identical components. In this report we present immunocytochemical data which indicate that the cortical granule population of S. purpuratus eggs is heterogeneous. Two monoclonal antibodies are shown to react to the spiral lamellae region of approximately 20% of the cortical granules, implying that the contents of the reactive granules differ from the contents of the majority of the population. An egg protein of greater than 320 kDa is recognized by the antibody. These antibodies also stain a 130-kDa protein expressed on the surface of primary mesenchyme cells in later development. Both antibodies recognize a post translational modification of this protein. This suggests that an antigenically similar epitope is present both on the 130-kDa primary mesenchyme cell-specific protein and in the cortical granules. To determine if the primary mesenchyme and cortical granule proteins are related, a fusion protein antibody specific for a region of the 130-kDa protein was used to stain unfertilized eggs. This antibody did not stain cortical granules. Thus, 20% of the cortical granules contain a molecule that has an epitope antigenically similar to the post-translational modification recognized in primary mesenchyme cells by the monoclonal antibodies. PMID- 3334713 TI - Effects of innervation on the distribution of acetylcholine receptors in regenerating skeletal muscles of adult chickens. AB - In order to determine the roles of nerves in the formation of clusters of acetylcholine receptors (AChRs) during synaptogenesis, we examined the distribution of AChRs in denervated, nerve-transplanted (neurotized) muscles and in regenerated skeletal muscles of adult chickens by fluorescence microscopy using curaremimetic toxins. In the denervated muscles, many extrajunctional clusters developed at the periphery of some of the muscle nuclei of a single muscle fiber and continued to be present for up to 3 months. The AChR accumulations originally present at the neuromuscular junctions disappeared within 3 weeks. In the neurotized muscles, line-shaped AChR clusters developed at 4 days after transection of the original nerve, but no change in the distribution of AChRs had occurred even at 2 months after implantation of the foreign nerve. The line-shaped AChR clusters were found to be newly formed junctional clusters as they were associated with nerve terminals of similar shape and size. Some of both the line-shaped and extrajunctional clusters were formed at least partly by the redistribution of preexisting AChRs. Finally, based on the above observations, the regenerating muscle fibers in normal muscles and in denervated muscles were examined: The extrajunctional clusters appeared in both kinds of muscles at 2 weeks after injury. Afterward, during the innervation process, the line-shaped AChR clusters developed while the extrajunctional clusters disappeared in the innervated muscles. In contrast with this, in the absence of innervation, only the extrajunctional clusters continued to be present for up to 3 months. These results demonstrate clearly that the nerve not only induces the formation of junctional clusters at the contact site, but also prevents the formation of clusters at the extrajunctional region during synaptogenesis. PMID- 3334715 TI - Laminin alters cell shape and stimulates motility and proliferation of murine skeletal myoblasts. AB - Proliferating skeletal myoblasts show multiple specific responses to laminin, one of the major glycoprotein components of basement membranes. Using MM14Dy myoblasts, a myogenic cell strain derived from a normal adult mouse skeletal muscle, we show in this study that substrate-bound laminin but not other matrix proteins such as collagens or fibronectin specifically and rapidly induces the outgrowth of cell processes, resulting in bipolar, spindle-shaped cells. This effect is independent from the presence of collagens or serum, and was also observed in primary cultures of fetal mouse skeletal myoblasts. The outgrowth of cell processes on laminin is associated with a dramatic stimulation of cell motility: MM14 myoblasts migrate about five times faster on laminin than on fibronectin. In another series of experiments the effect of laminin and fibronectin on thymidine uptake and proliferation of myoblasts was tested. On top of a type I collagen substrate which was provided to ensure complete adhesion even at low doses of laminin or fibronectin, laminin stimulated myoblast proliferation and incorporation of [3H]thymidine in a dose-dependent manner. The stimulation is two- to threefold higher than on dishes coated with equivalent amounts of fibronectin and is observed both in the presence and in the absence of serum. These results suggest that laminin, a major component of the muscle basal lamina, may be actively involved in the development and regeneration of skeletal muscle. PMID- 3334714 TI - Immunoreactivity for laminin in the developing ventral longitudinal pathway of the brain. AB - The first long tract to form in the brain of a vertebrate embryo is the ventral longitudinal pathway. In order to investigate what chemical cues may guide nerve growth cones along this pathway, affinity-purified antibodies to laminin and collagen type IV were used to stain sections of mouse embryos from Embryonic Days 8 through 17. A monoclonal anti-neurofilament antibody was used to show the development of the ventral longitudinal pathway in relationship to immunoreactivity for laminin and collagen type IV. At Day 8 fluorescent immunoreactivity for laminin is bright in the external limiting membrane of the neural tube, but the neuroepithelium does not show bright laminin or neurofilament immunoreactivity. At E9 the ventral longitudinal pathway is forming and punctate immunoreactivity for laminin is present on the surfaces of neuroepithelial cells in the marginal zone, through which axons of the ventral pathway extend. Punctate immunofluorescence for laminin remains concentrated in the marginal zone on Days E10 through E14, but on E16 punctate immunofluorescence was much reduced, although immunoreactivity for laminin remained bright in the maturing pial and arachnoid membranes and on blood vessels in the brain. Immunoreactivity for collagen type IV was strong in the external limiting membrane and on blood vessels, but never showed concentrated punctate immunofluorescence in the marginal zone. These results indicate that laminin may be available on cell surfaces and in extracellular spaces as an adhesive ligand for growth cones during the formation of the ventral longitudinal pathway. PMID- 3334716 TI - Importance of glutathione in the acquisition and maintenance of sperm nuclear decondensing activity in maturing hamster oocytes. AB - Sperm nuclear decondensing activity in mammalian oocytes is dependent upon the maturational state of the oocyte. It is maximal in mature, metaphase II oocytes and minimal or absent in immature germinal vesicle (GV) and fertilized pronuclear oocytes. Previous studies suggested that this difference may be due to the relative ability of an oocyte to reduce the protamine disulfide bonds in the sperm nucleus. The results of this study show that mature hamster oocytes contain significantly more glutathione (GSH), about 8 mM, and hence more disulfide reducing power, as compared with GV (4 mM) or pronuclear (6 mM) oocytes. Furthermore, the acquisition of sperm nuclear decondensing activity by maturing oocytes can be prevented or delayed by blocking GSH synthesis with L-buthionine S,R-sulfoximine during the early stages of oocyte maturation. This is the first evidence that modulation of GSH levels during oocyte maturation and fertilization may be a mechanism by which sperm nuclear decondensing activity is regulated. PMID- 3334717 TI - Endogenous lectin secretion into the extracellular matrix of early embryos of Xenopus laevis. AB - An endogenous galactoside-binding lectin with subunit molecular weight of 43,000 45,000, previously detected in unfertilized eggs of Xenopus laevis, persists at high levels in embryos through gastrulation. During embryonic development the lectin is found in cytoplasmic vesicles, and then is secreted into extracellular matrix which is prominent around the blastopore and on the roof of the blastocoel. The lectin is also found in the extracellular material in the developing neural fold. The presence of lectin at sites of active morphogenetic movements raises the possibility that it participates in the formation of an extracellular matrix that influences these processes. PMID- 3334718 TI - Developmental regulation of a constitutively expressed mouse mRNA encoding a 72 kDa heat shock-like protein. AB - Multiple heat shock cognate (hsc70) cDNA clones were isolated from the mouse embryonal carcinoma cell line F9. They all encode a single 72-kDa protein, which is constitutively expressed in all mouse cell lines and tissues tested, and which is only slightly induced by hyperthermia. hsc70 RNA is very abundant in F9 stem cells and brain, but very little is found in 14-day-old embryos. Upon differentiation of F9 stem cells induced by retinoic acid and cyclic AMP, expression of the hsc70 gene decreases only slightly, suggesting that hsc70 is highly expressed in early mouse development and is then down-regulated towards the end of embryogenesis. In adult tissues only the brain retains the high level of hsc70 gene expression found in F9 stem cells. We also show that expression of hsc70 protein and clathrin is uncoupled in F9 cells, indicating that the uncoating activity of coated vesicles may not be the only function of hsc70 protein. PMID- 3334719 TI - Dimethyl sulfoxide interferes with in vitro differentiation of chick embryo endochondral chondrocytes. AB - Dedifferentiated chondrocytes derived from 6-day-old chick embryo tibiae when transferred on agarose, revert to the chondrocytic phenotype and mature to hypertrophic, type X collagen-producing chondrocytes (Castagnola et al. (1986). J. Cell Biol. 102, 2310-2317). The continuous presence of 180 mM dimethyl sulfoxide (DMSO) during the culture specifically inhibited synthesis of type X collagen and accumulation of its mRNA. The synthesis of the cartilage-specific type II collagen and the level of its mRNA were essentially unchanged in treated and control untreated cells. PMID- 3334720 TI - Analysis of type II collagen RNA localization in chick wing buds by in situ hybridization. AB - Type II collagen is a major component of cartilage extracellular matrix. Differentiation of mesenchyme into cartilage involves the cessation of type I collagen synthesis and the onset of type II collagen synthesis. Solution hybridization of mRNA isolated from chick limb buds with a cDNA probe to type II collagen mRNA showed the presence of small amounts of type II collagen message in mesenchymal chick limbs. We have examined the localization of type II collagen mRNA in mesenchymal chick wing buds by in situ hybridization using single stranded RNA probes. Our results show a small but detectable amount of type II collagen RNA distributed uniformly in early limbs until the first precartilage condensations form at stage 22. This is interesting because it is known that mesenchyme isolated from chick wing buds has the capacity to undergo chondrogenesis in culture, even if taken from nonchondrogenic areas of the limb. At stage 23, type II collagen mRNA is found at significantly increased levels in the cells of the precartilage condensation when compared to the other limb cells. As chondrogenesis proceeds, the amount of type II collagen RNA increases even more in cells of the cartilage elements. The signal in the peripheral tissue is indistinguishable from background. These results show that type II collagen message exists at low levels in cells throughout the mesenchymal chick wing bud, until the formation of the condensation results in an elevation of type II mRNA in the prechondrogenic cells found in the core of the limb. PMID- 3334722 TI - Sheep major histocompatibility (OLA) complex: linkage between a scrapie susceptibility/resistance locus and the OLA complex in Ile-de-France sheep progenies. AB - As seen on their family trees, Ile-de-France sheep with scrapie show genetic susceptibility to this disease, which is transmitted via scrs, an autosomal recessive gene. Scrapie occurred in homozygous recessive sheep, whereas the presence of the dominant resistance allele Scrr sufficed to prevent this disease in heterozygous animals. This hypothesis, previously proposed by Parry (1962), was tested in a study involving 133 crossings of sheep of different genotypes, and verified in the observed progenies. In a contaminated environment, susceptibility to the disease seemed to be transmitted by the scrs gene, whose frequency was increasing and varied in different progenies: the gene was propagated by inbreeding combined with selection; scrapie did not appear in the progeny of a homozygous resistant ram with the Scrr/Scrr genotype. On the family trees, linkage between the Scr locus and the OLA-A and -B loci is clearly visible; it often allowed the transmission of resistance or susceptibility haplotypes to be detected by OLA typing and followed from one generation to the next. The Scrr, OLA-A4, B6 haplotype was not found in any diseased sheep born before 1979, but was propagated by healthy sheep. During and after 1979, several recombinations of this haplotype were observed, giving a recombined haplotype with reciprocal linkage (scrs, OLA-A4, B6), disseminated by one sire in particular. The rate of recombination of Scr and OLA loci is estimated to be between 11 and 16%. The possibility of early selection against the disease without loss of qualities desired by the breeder is discussed. PMID- 3334723 TI - Class III gene rearrangements in Thai/Chinese supratypes containing null or defective C4 alleles. AB - Class III gene rearrangements have been examined in Thai/Chinese individuals with supratypes bearing defective or null C4 alleles. Genomic DNA from C4 null supratypes was probed with an almost full-length 21-OH probe following digestion with Taq I and Kpn I. The HLA-B17 C4A3 BQ0 BfS DR3 Thai/Chinese supratypes (which may be associated with insulin-dependent diabetes mellitus in Orientals) lacks a 3.2 kb Taq I and a 3.9 kb Kpn I fragment hybridizing with the 21-OH probe. Similar gene rearrangements are found in Caucasoid diabetogenic supratypes HLA B18 C4A3 BQ0 BfF1 DR3 and HLA-B8 C4AQ0 B1 BfS DR3. Interethnic comparisons suggest that class II and class III interactions may be important in disease susceptibility. By contrast, neither of two Thai/Chinese supratypes with C4AQ0 appear to have major class III gene rearrangements; disease association studies will determine the significance of C4 deficiency per se. As in Caucasoids, the electrophoretically fast C4 allele, C4A6, in Orientals has been shown to correlate with a 12 kb Bgl II fragment hybridizing with a C4 probe. It is likely that the HLA-B17 C4A6 B1 BfS DR7 supratype marks a highly conserved MHC chromosomal segment. PMID- 3334721 TI - Transcripts of the Drosophila blastoderm-specific locus, terminus, are concentrated posteriorly and encode a potential DNA-binding finger. AB - The commitment of cells to specific fates, as well as the transitions in the cell cycle and transcription that occur at the cellular blastoderm stage of Drosophila embryogenesis, suggest that there are genes with unique functions expressed specifically at this stage. In an attempt to identify such genes, we used molecular screening to isolate several loci which encode blastoderm-specific transcripts (Roark et al., (1985). Dev. Biol. 109, 476-488). We report here the complete nucleotide sequence of one of these genes, terminus (ter), which maps to 75C1,2. The predicted ter protein possesses a transcription factor IIIA (TFIIIA) like putative Zn-binding, DNA-binding finger. The ter RNA, detected by in situ hybridization, is distributed uniformly in the embryo during the syncytial blastoderm stage, and then becomes more concentrated in the posterior during the late cellular blastoderm stage. During gastrulation, the RNA is most concentrated in the amnioproctodeal invagination; it is also found at a lower concentration in the ventral furrow and in the anterodorsal neurogenic region. By the end of germ band extension, ter RNA is no longer detected. PMID- 3334724 TI - The locus controlling liver GM1(NeuGc) expression is mapped 1 cM centromeric to H 2K. AB - The polymorphic variation of liver GM1 (NeuGc) ganglioside was found in inbred strains of the mouse. The genetic analysis using C57BL/10 (GM1-negative) and SWR (GM1-positive) mice revealed that a single autosomal gene (Ggm-1) was involved in the expression of liver GM1(NeuGc) and that C57BL/10 mice lacking GM1(NeuGc) expression carried a defective gene on Ggm-1. Since our previous study on H-2 congenic mice indicated that Ggm-1 was linked to the H-2 complex, in this study we measured recombination frequencies among Ggm-1, Glo-1 and H-2K in the backcross progeny between (C57BL/10 X SWR)F1 and C57BL/10. Ggm-1 was mapped 1 cM centromeric to H-2K on chromosome 17. PMID- 3334725 TI - Increased Mr 60,000 protein phosphorylation is correlated with neocortical neurofibrillary tangles in Alzheimer's disease. AB - Increased Mr 60,000 protein phosphorylation has been found in the cytosol fraction of brain tissue from Alzheimer's disease patients. A correlation between this biochemical change and the morphologic abnormalities found in Alzheimer's disease was sought. Three neuropathologic features were studied: neurofibrillary tangles and neuritic plaques, findings characteristic of Alzheimer's disease, and gliosis, a non-specific change. The number of tangles correlated well with the extent of Mr 60,000 protein phosphorylation (p less than 0.001); but the number of plaques did not. To investigate the possibility that gliosis causes the increased Mr 60,000 protein phosphorylation, cases of Pick's disease and multi infarct dementia were also studied. The levels of Mr 60,000 protein phosphorylation in these cases were comparable to those seen in normal controls. These findings suggest that the increased Mr 60,000 protein phosphorylation is closely related to diseased, tangle-bearing neurons and is not directly related to neuritic plaque formation or secondary gliosis. PMID- 3334726 TI - A quantitative assessment of microvessel ultrastructure in C6 astrocytoma spheroids transplanted to brain and to muscle. AB - Normal blood vessels invading a growing neoplasm undergo dramatic changes in morphology. Whether vessel characteristics are dictated entirely by the tumor, or from developmental restrictions in normal vessels from which tumor vessels originate is not known. To address this question we challenged two morphologically different types of capillaries (brain and muscle) with the same tumor environment (C6 astrocytoma), and quantified the invading vessel morphology. A vascular spheroids of C6 astrocytoma cells were implanted singly into rat cerebral cortex or iliacus muscle. Microvessels from the tumor, peritumoral tissue and control tissue were examined ultrastructurally and quantified. Tumor vessels differed significantly from host vessels but not from each other, regardless of implantation site. Neoplastic vessels were thick-walled relative to normal host vessels, had low densities of mitochondria and vesicular structures, and had both fenestrations and enlarged junctional clefts characteristic of highly permeable vessels. Control brain vessels were typically thin-walled, had a high density of mitochondria, a low density of endothelial vesicles and continuous tight junctions. Control muscle vessels were thin-walled with a low density of mitochondria, high density of vesicles and junctional zones with occasional enlarged clefts. Peritumoral vessel morphology was intermediate between that of tumor and the corresponding control tissue. We propose that C6 astrocytoma cells influence invading endothelial cells to develop a permeable phenotype radically different from host tissue endothelium, and host vessel phenotype does not influence tumor vessel morphology. PMID- 3334728 TI - The effect of cryopreservation on canine menisci: a biochemical, morphologic, and biomechanical evaluation. AB - This study evaluated the effect of cryopreservation on the structural organization, biosynthetic activity, and material properties of canine menisci. The menisci were cryopreserved by incubating them in a 4% solution of dimethyl sulfoxide (DMSO) in physiologic media and freezing them to -100 degrees C using a controlled rate freezing system. The menisci were then stored for varying periods of time from zero to 12 weeks in liquid nitrogen (-196 degrees C). Following rapid thawing, changes in the histological appearance and biosynthetic activity of the menisci were evaluated as functions of storage time. In addition, the effects of the cryopreservation process on the tensile strength and modulus of the meniscal tissue were assessed. Although cryopreservation and short-term storage did not appear to affect the morphological appearance or biomechanical character of the menisci, biosynthetic activity, as determined by Na2S35SO4 incorporation, was diminished to less than 50% of normal control values immediately following cryopreservation and thawing. Autoradiographic examination of these tissues revealed that only approximately 10% of the meniscal cells were metabolically active, however, indicating that a marked increase in the metabolic activity of individual cells occurs following the freeze-thaw cycle. Total metabolic activity continued to decline with storage time. PMID- 3334729 TI - Protease inhibitors decrease rabbit cartilage degradation after meniscectomy. AB - In vitro proteoglycan (PG) synthesis and release were measured on cartilage removed from rabbit knees within 1 week of meniscectomy. Three days following partial lateral meniscectomy, 72% of the femurs and 82% of the tibias had visible ulcers. Cartilage from the weight-bearing areas incorporated 2.0-2.9 times more 35S-sulfate in vitro than cartilage from the opposite, unoperated knees. 3H thymidine incorporation was 2.5-3.4 times higher for surgical than control groups. 35S-sulfate incorporation by the surgical group was inhibited by 22% in the presence of 10(-4) M U24522, an inhibitor of rabbit chondrocyte metalloprotease (CMP). 3H-thymidine incorporation by the surgical group was inhibited by 28% by 10(-4) M U24522. In vitro PG release from cartilage removed 2 days after surgery was 1.6-3.7 times higher for the surgical than the control group. PG release by the surgical group after 22 h of incubation was reduced to the control level by three CMP inhibitors, U24278, U24279, and U24522. PG release by cartilage from the nonsurgical group was also reduced by these compounds at 22 h. These results suggest that both the anabolic and catabolic processes that are stimulated by surgery can be isolated in vitro and that CMP may be involved in the catabolic process. PMID- 3334727 TI - Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients. AB - Perikaryal collections of intermediate filaments have been described in the anterior horn motoneurons of patients with amyotrophic lateral sclerosis (ALS), but these inclusions have generally been considered rare and mainly associated with the familial form of ALS. Using the monoclonal antibody NF2F11, which recognizes phosphorylated neurofilament epitopes, we showed that focal collections of neurofilaments in anterior horn motoneurons were a characteristic finding in sporadic as well as in familial ALS; they were present in seven of nine ALS patients, but in none of nine control spinal cords. These neurofilamentous collections are not cross-reactive with antibodies directed against paired helical filaments and the microtubule associated protein tau. In addition, diffuse staining for phosphorylated neurofilament epitopes in chromatolytic anterior horn perikarya was significantly more frequent in ALS patients than in controls. PMID- 3334730 TI - Kinetics of osmotic water movement in chondrocytes isolated from articular cartilage and applications to cryopreservation. AB - The ability of chondrocytes to survive conditions encountered during cryopreservation depends on the responses of the cells to the physiochemical changes that result when water is removed from the environment of the cells in the form of ice. Cellular responses are therefore closely related to the osmotic permeability properties of the plasma membrane. In order to optimize the conditions for cryopreservation of chondrocytes, osmotic properties of the chondrocyte membrane were determined from the kinetics of volume change in hypertonic solutions at different temperatures. The hydraulic conductivity of the plasma membrane was 0.305 +/- 0.025 micron3/micron2/min/atmosphere at 24 degrees C, with an Arrhenius activation energy of 8.06 kcal/mol. These values are similar to those reported for other cell types, but the osmotically inactive volume of the chondrocytes (0.41 +/- 0.04) was significantly higher than for other cells, implying that chondrocytes have a higher dry weight ratio or that they contain a higher proportion of osmotically inactive or bound water. These results were used to calculate the osmotic responses of chondrocytes at low temperatures and to predict that the least damaging cooling rate for isolated chondrocytes in the absence of cryoprotective compounds is 10 degrees C/min. The ultimate goal of this study is the development of an analytical model applicable to the optimization of techniques for cryopreservation of intact cartilage and other tissues. PMID- 3334731 TI - Mathematical analysis of computed carpal models. AB - The computed carpal models from digital computed tomography (CT) data obtained in this study compare favorably to natural anatomy. A new application of algebraic analysis of this data provides mathematical markers from which to calculate the position and orientation of each carpal bone. When the origin of the spatial coordinates of a carpal bone is transferred to the centroid of the bone, the data can be treated as three-dimensional pattern vectors describing its surface. It is then possible to calculate vectors that are the principal axes of the geometry. These axes provided references that were used to calculate position and orientation of the carpal bones in three wrist specimens. Comparisons of volumes, surface areas, and sizes and proportions of five computed images of each carpal bone from two of these wrists demonstrate the reliability of the technique. The analysis of CT scans of ceramics with known boundaries allows an estimation of its accuracy. The technique is well suited to the future study of normal wrist kinematics and pathological conditions. PMID- 3334732 TI - Pressure recording in the subacromial bursa. AB - The microcapillary infusion (MCI) technique was evaluated in monitoring pressure in the subacromial bursa in 30 shoulders in healthy volunteers. The total pressure in the bursa was studied as the volunteers held their arms at rest and as they lifted their arms and held them lifted with or without a weight of 1 kg in the hands. The pressure in the bursae at rest averaged 8 mm Hg and was found stable during a 40-min period. When the arms were lifted, the average bursa pressure increased from 8 to 39 mm Hg. As the arms were held up, the weights were put in the hands, and the average bursa pressure then further increased to 56 mm Hg. When the infusion catheters were repeatedly flushed, during a period of 5 min and with a total of 1.2 ml of saline, the average bursa pressure doubled regardless of arm position and load in the hands. The compliance of the bursae decreased from 0.09 to 0.04 ml/mm Hg when the arms were lifted and from 0.04 to 0.02 ml/mm Hg when the arms were lifted and the hands were loaded. The MCI method was found suitable for recording pressure in the subacromial bursa during exercise. PMID- 3334733 TI - Spinal deformity and back surface asymmetry in idiopathic scoliosis. AB - Stereo radiography and stereotopography were used to record simultaneously the three-dimensional spinal and back surface shape of 141 patients with a clinical diagnosis of adolescent onset idiopathic scoliosis. Radiography confirmed 80 patients with single lateral curves (Cobb angle 5-87 degrees); 59 with double curves (Cobb angle 5-61 degrees), and two patients with triple curves. Orientation of each vertebra was measured by the lateral deviation from the spinal axis and the axial rotation. For each curve detected, the Cobb angle, the maximum deviation, the maximum axial rotation, and the sagittal plane curvature was measured. Topographic data were used to generate a profile of a cross-section through the back of each vertebral level. This section was characterized by its axial rotation, deviation of its midpoint from the spinal axis, and area symmetry about the midpoint. Maximum values of these measurements in the region of each radiographic scoliosis curve were noted. Regression and correlation analysis showed (for each curve) a high correlation of apical vertebral lateral deviation with back surface axial rotation (r = 0.79) and with vertebral axial rotation (r = 0.79). The back surface rotation was less than vertebral rotation in magnitude, however, by a mean factor of 0.55. The measurement of the back surface asymmetry that gave the highest correlation with the skeletal deformity was the axial rotation. Relationships between skeletal and surface measures were similar for curves in thoracic and lumbar regions and for patients with single and double curves. There is potential for clinical application of surface measurement techniques to prescription of orthoses and monitoring of changes due to progression or treatment. PMID- 3334734 TI - Serum-free culture of rabbit meniscal fibrochondrocytes: proliferative response. AB - We have formulated a serum-free medium capable of supporting DNA synthesis in rabbit meniscal fibrochondrocytes at a level equivalent to 10% fetal bovine serum (FBS). The medium consists of a 1:1 mixture of Dulbecco's Modified Eagle's Medium and Ham's F-12 medium supplemented with transferrin (1 microgram/ml), selenium (1 pg/ml), trace metal mix (1:100), dexamethasone (100 ng/ml), insulin-like growth factors I and II (50 ng/ml each), pituitary fibroblast growth factor (100 ng/ml), and lactalbumin hydrolysate (2 micrograms/ml). Endothelial cell growth supplement could be substituted for lactalbumin hydrolysate to obtain similar results. Ventrex PC-1, a commercially available, low-protein, serum-free medium, was found to support proliferation of fibrochondrocytes but not as well as 10% FBS or our medium formulation. Lipid supplements, which are known to support the serum-free growth of hyaline chondrocytes, were found to be either of no value or antagonistic for the culture of fibrochondrocytes. Likewise, vitamin E alone, progesterone, putrescine, and hydrocortisone were also without benefit in our culture system. The cells had a more chondrocytic morphology when grown in defined medium as opposed to 10% FBS. The results of this study should now make it possible to identify and quantitate those factors necessary to affect meniscal repair by utilizing further techniques in vitro. PMID- 3334736 TI - Mechanical stresses and endochondral ossification in the chondroepiphysis. AB - In 1911, Gebhardt used a photoelastic model to relate mechanical stresses to the ossification pattern of the chondroepiphysis. Pauwels later conducted a photoelastic study using the same model geometry to develop a theory that the secondary ossific nucleus originates at a position of high-magnitude hydrostatic pressure where the shear stresses are zero. We conducted two-dimensional finite element analyses of the model used by Gebhardt and Pauwels. We demonstrate that Pauwels's photoelastic results are correct but are based on the imposition of incorrect boundary conditions. When more realistic boundary conditions were used, the finite element results changed dramatically. These results suggest that (a) the ossific nucleus appears in an area of high shear (deviatoric) stresses; (b) the edge of the advancing ossification front (zone of Ranvier or ossification grove) also experiences high shear stresses; and (c) the joint surface, where articular cartilage forms, is exposed to high-magnitude hydrostatic compression. These findings support the theory proposed by Carter and associates that intermittently applied shear stresses (or strain energy) promote endochondral ossification and that intermittently applied hydrostatic compression inhibits or prevents cartilage degeneration and ossification. PMID- 3334735 TI - External ultrasound can generate microampere direct currents in vivo from implanted piezoelectric materials. AB - Under development is an internal fixation plate that incorporates a piezoelectric element to generate current when excited mechanically by either weight bearing or external application of ultrasound. The intent is to deliver this current to electrodes at a fracture or osteotomy site to aid in prevention or treatment of nonunion. The present study examines quantitatively the ability of external ultrasound to generate current from small piezoelectric ceramic elements implanted in tissue. An ultrasonic transducer (2.25 MHz, 10-20 V input, less than 10 mW/cm2 output) was employed to excite small test coupons of a piezoelectric ceramic in vitro and in vivo with various materials, including water, PVC gel, cortical bone, and living soft tissues, interposed. In all instances, it was possible to generate currents of up to 20 microA after rectification; currents up to 1 mA were achieved in some cases. The work indicates that external ultrasonic energy could effectively power small internal devices designed to stimulate bone healing, without the need for implanted batteries or percutaneous leads. PMID- 3334737 TI - Strain rate and mineral content in fracture models of bone. AB - I reanalysed data from my previous work to determine the extent to which a model for the loading-rate dependence of the fracture of cortical bone, put forward by Carter and Caler, fits this independently derived data set. In particular, the extent to which the generality of the model is vitiated by its ignoring the effect of mineralisation on strength was tested. The model was rather strongly corroborated. In addition, the reanalysed data show that yield strain is strongly strain-rate dependent, but that Young's modulus is rather unvarying over physiological strain rates. The implications of this for hypotheses concerning fracture of bone are discussed. PMID- 3334738 TI - Stresses in plated long-bones: the role of screw tightness and interface slipping. AB - Using a three-dimensional finite element model of a plated long bone, we studied the influence of screw tightness, sliding frictional interfaces, and loading magnitude on the stresses within the plated bone. The model incorporated frictional interface elements that allowed stress-free separation under tensile loading to occur between the plate and bone and between the screw heads and the plate. The applied loading stimulated both static preloads created by tightening the screws that secure the plate to the bone and physiologic loads created by activity. Initial screw tightening with plate application created regions of bone hydrostatic compressive stress that may be partly responsible for ischemia under the plate. The inclusion of frictional interfaces resulted in a nonlinear relationship between physiologic loan and bone strain that was dependent on screw tightness. This nonlinear response correlated well with the results of previous in vitro studies showing that slippage between the plate and the bone can occur at physiologic load levels. The results showed that the effect of such slippage can be at least as important as plate material, rigidity, and placement in determining the degree of stress shielding. The results also indicated that previous plated bone models that assumed tight interfaces may have overestimated the extent of mechanical stress shielding. PMID- 3334739 TI - Bioimplant surfaces: binding of fibronectin and fibroblast adhesion. AB - The adhesion of baby hamster kidney 21C/13 fibroblasts to surfaces of passivated titanium, carbon fibers, bioactive glasses B5 and B6, fibronectin-precoated passivated titanium, and fibronectin-precoated B6 was quantified. The order of adhesive cell avidity for the uncoated surfaces was passivated titanium (greatest), B6 and carbon fibers (intermediate), and B5 (least). Precoating with fibronectin enhanced the adhesive characteristics of fibroblasts on passivated titanium and B6 by 74% and 118%, respectively. PMID- 3334740 TI - Acute staphylococcal septic arthritis: the effect of cloxacillin therapy in an avian model. AB - An experimental model of acute staphylococcal septic arthritis in chickens was used to study the effect of different therapeutic regimens of the antibiotic cloxacillin on the natural history of the disease. Three different therapeutic regimens were used in order to assess the effect of increasing the frequency and of delaying the commencement of administration. The results were assessed by measurement of animal growth rate, clinical condition, bacterial and leukocyte counts in synovial fluid, and histological appearance. An inadequate dosage regimen (a single daily dose) prevented spread of bacteria but did not control abscesses. Delay in commencing treatment permitted persistence and spread of abscesses with destruction of the secondary (epiphyseal) ossification center and even transphyseal spread into metaphyseal bone. Repair by fibroblasts was mainly seen in articular and epiphyseal cartilage but was not seen in the epiphyseal ossification center during the duration of the experiments (up to 18 days). Synovial fluid sampling with measurement of leukocyte and bacterial concentrations appears to be a useful guide to the effectiveness of treatment, because the numbers of cells correlate with the pathological process. PMID- 3334741 TI - Cell populations of tendon: a simplified method for isolation of synovial cells and internal fibroblasts: confirmation of origin and biologic properties. AB - Tendons transmit the force of muscle contraction to bone to effect limb movement. Special structural and biological properties of tendon have developed to facilitate force transmission. The tendon has a complex organization of cells surrounding the collagen bundles inside tendon as well as at the tendon surface. Internal cells may act to maintain the bulk of the collagen in tendon. External cells in the epitenon may provide lubrication for tendon gliding. To develop better understanding of these processes and the roles the cell populations play, we isolated cells from the surface and interior of tendon and studied them in vitro. Flexor tendons from 8-week-old white Leghorn chickens were separated into two distinct cell populations: the outer synovial cells and the fibroblasts more internal in tendon. These cell populations were discernible by their locations in the intact tendon, determined by sequential enzymatic and physical release from their substrata. Initially, some cells eluted in Hanks' salt solution (HSS) (population 1); then synovial cells were released after a 2-min treatment with 0.5% collagenase (population 2). Next, a population of synovial cells was released in high yield by treatment with 0.25% trypsin (step III, population 3). Step III, population 3 cells were used as synovial cells (SCs). Next, a population of SCs and fibroblasts were released by scraping with a rubber policeman (population 4). Subsequently, fibroblasts were released after incubation with 0.5% collagenase (population 5). A more direct procedure (procedure 2) to isolate the synovial and internal tendon cells involved treatment in 0.5% collagenase followed by sedimentation at 900 g. Cells that sedimented were largely fibroblasts, whereas the cells that remained at the top of the tube were largely SCs. Cells designated as SCs, isolated by procedure 2, most likely contained surface cells from epitenon and internal interfascicular cells from endotenon and paratenon. Surface tendon cells separated by sequential enzymatic and physical release from their substrata (by procedure 1) had all the following characteristics: distinct subpopulations of cells based on morphology; presence of cytoplasmic, lipid-containing vesicles; decreased sensitivity to trypsin; and reduced generation time as compared with that of internal fibroblasts. Conversely, the internal fibroblasts (IFs) appeared to represent a more uniform population based on morphological characteristics. PMID- 3334742 TI - Viability of ligaments after freezing: an experimental study in a rabbit model. AB - Our purpose in this study was to assess ligament fibroblast viability after freezing by quantifying the subsequent ability of fibroblasts to synthesize collagen in vitro. Both medial collateral ligament (MCL) complexes from 40 adolescent rabbits were studied. Collagen production was determined by in vitro incubation of ligaments in 3H-proline (a collagen precursor) and subsequent analysis of 3H-hydroxyproline (a marker of newly synthesized collagen). Autoradiographs determined the distributions of ligament cell activity. All right MCL complexes served as fresh controls, providing a baseline of collagen production. Each left MCL was assigned to an experimental group and was either incubated fresh (10 animals); "killed" by drying, multiple freeze thawing, or cycloheximide (six animals); or slowly frozen at -70 degrees C without cryoprotection (24 animals). Collagen production of rapidly thawed ligaments was studied by proline incubation at 1 day, 9 days, or 6 weeks after freezing and was compared with that of contralateral fresh controls. Results demonstrate that some cells in the substance of these rabbit ligaments retained the ability to synthesize collagen in vitro after being frozen for up to 6 weeks. Mean collagen production of frozen ligaments was decreased, but tests of mean and median values as well as ratios were statistically similar to fresh contralateral ligaments in all animals. This postfreezing ligament cell survival and collagen production after -70 degrees C storage may have implications for ligament transplantation. PMID- 3334743 TI - Characterization of a recombinant vaccinia virus expressing human melanoma associated antigen p97. AB - p97 is a cell surface glycoprotein expressed at high levels in most human melanomas but present only in trace amounts in normal adult tissues. We are interested in exploring the possibility of using recombinant vaccinia virus to express a specific tumor-associated antigen as a vaccine against human cancer. To this end, we constructed a recombinant virus, v-p97NY, which contains the entire coding sequence for p97 under the control of the vaccinia virus 7.5K promoter. Upon infection of tissue culture cells, v-p97NY expressed high levels of a membrane-bound glycoprotein immunoreactive with a p97-specific monoclonal antibody. Immunization of mice with this recombinant elicited high-titered antibodies against p97. Spleen cells isolated from these mice proliferated in vitro when stimulated either with purified p97 protein or with syngeneic cells expressing p97 antigen. Delayed-type hypersensitivity was also observed in immunized mice after challenge with p97-expressing cells. These findings indicate the potential usefulness of v-p97NY and similar recombinants in tumor immunotherapy. PMID- 3334744 TI - Antibody-mediated growth of influenza A NWS virus in macrophagelike cell line P388D1. AB - We investigated the internalization and growth of influenza A NWS virus in macrophagelike P388D1 cells. Flow cytometric analysis using fluorescein isothiocyanate-labeled virus showed that the attachment of normal rabbit serum exposed virus (NS-V) to neuraminidase (NA)-treated cells was noticeably limited compared with that to untreated cells. However, rabbit antiserum-exposed virus (AS-V) could attach equally well to both cells. Virus coated with Fab prepared from antiviral immunoglobulin G could not attach. These data suggest that the NWS virus can infect P388D1 cells in one of two ways, via viral or via Fc receptors, depending on the presence of antibodies. The NS-V could grow in the untreated cells, but not in the NA-treated cells. The highest growth of AS-V in the NA treated cells was observed at an antibody concentration showing 50% plaque reduction titer. Growth was exponentially decreased toward the lower and higher dilutions of antibodies. By using three different immunoglobulin G subclasses of monoclonal antibodies against hemagglutinin, it was demonstrated that both Fc receptors I and II could take part in this phenomenon. The presence of 20 mM NH4Cl inhibited the growth of both AS-V and NS-V, suggesting that the intracellular pathways after internalization via Fc or viral receptors are similar. These data indicate that the concentration of antibodies has a critical role on the antibody-mediated growth of influenza virus in macrophages. PMID- 3334745 TI - La Crosse virus infection of mammalian cells induces mRNA instability. AB - La Crosse virus infection of BHK cells leads to a dramatic shutoff of not only host protein synthesis but also viral protein synthesis later in infection. This shutoff can be accounted for by the loss of the cytoplasmic cellular and viral mRNAs. The induction of mRNA instability requires extensive virus replication, since when cycloheximide is added early in infection the preexisting viral and cellular mRNAs do not decrease upon incubation of the cultures. Pretreatment of the cultures with actinomycin D does not affect the ability of La Crosse virus infection to induce mRNA instability, and examination of the rRNAs shows no evidence of specific degradation due to activation of the interferon-associated latent RNase. The induction of mRNA instability therefore does not appear to operate through an interferon pathway. Viral mRNA synthesis, on the other hand, is not turned off during infection, and the cap-dependent endonuclease involved in viral mRNA initiation may be responsible for the mRNA instability. PMID- 3334747 TI - Nonpermissivity of human peripheral blood lymphocytes to adenovirus type 2 infection. AB - The capacity of freshly explanted human peripheral blood lymphocytes (PBL) to support the replication of human adenovirus type 2 (Ad2) was investigated. Unlike other types of human cells, PBL were found to be highly nonpermissive. Ad2 adsorbed 30 to 40% of both T and non-T cells. Virus uncoating was very slow and inefficient, resulting in a 40-fold reduction compared with HEp-2 cells. On a population basis, viral DNA synthesis was reduced 460-fold and infectious virus production was reduced 10(6)-fold. Only 0.35% of PBL produced infectious centers, yielding 0.8 PFU per infected cell. Phytohemagglutinin stimulation increased DNA synthesis 23-fold, infectious centers 11-fold, and virus yield 14-fold. We conclude that resting human PBL are highly nonpermissive to Ad2 infection and that phytohemagglutinin can only marginally lift this nonpermissiveness. PMID- 3334746 TI - Molecular dissection of cis-acting regulatory elements from 5'-proximal regions of a vaccinia virus late gene cluster. AB - Promoter elements responsible for directing the transcription of six tightly clustered vaccinia virus (VV) late genes (open reading frames [ORFs] D11, D12, D13, A1, A2, and A3) from the HindIII D/A region of the viral genome were identified within the upstream sequences proximal to each individual locus. These regions were identified as promoters by excising them from the VV genome, abutting them to the bacterial chloramphenicol acetyl transferase gene, and demonstrating their ability to drive expression of the reporter gene in transient expression assays in an orientation-specific manner. To delineate the 5' boundary of the upstream elements, two of the VV late gene (A1 and D13) promoter: CAT constructs were subjected to deletion mutagenesis procedures. A series of 5' deletions of the ORF A1 promoter from -114 to -24 showed no reduction in promoter activity, whereas additional deletion of the sequences from -24 to +2 resulted in the complete loss of activity. Deletion of the ORF A1 fragment from -114 to -104 resulted in a 24% increase in activity, suggesting the presence of a negative regulatory region. In marked contrast to previous 5' deletion analyses which have identified VV late promoters as 20- to 30-base-pair cap-proximal sequences, 5' deletions to define the upstream boundary of the ORF D13 promoter identified two positive regulatory regions, the first between -235 and -170 and the second between -123 and -106. Background levels of chloramphenicol acetyltransferase expression were obtained with deletions past -88. Significantly, this places the ORF D13 regulatory regions within the upstream coding sequences of the ORF A1. A high-stringency computer search for homologies between VV late promoters that have been thus far characterized was carried out. Several potential consensus sequences were found just upstream from RNA start sites of temporally related promoter elements. Three major conclusions are drawn from these experiments. (i) The presence of promoters preceding each late ORF supports the hypothesis that each is expressed as an individual transcriptional unit. (ii) Promoter elements can be located within the coding portion of the upstream gene. (iii) Sequence homologies between temporally related promoter elements support the notion of kinetic subclasses of late genes. PMID- 3334748 TI - Identification of point mutations in the envelope gene of Moloney murine leukemia virus TB temperature-sensitive paralytogenic mutant ts1: molecular determinants for neurovirulence. AB - ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, induces hind-limb paralysis in mice. The DNA of both the ts1 and Moloney murine leukemia virus TB env genes has been sequenced, and the encoded amino acid sequences have been deduced from the DNA sequences. Four amino acids in the ts1 envelope protein have been identified which may be responsible for the ts1 phenotype, which includes temperature sensitivity, nonprocessing of Pr80env, and neurovirulence. PMID- 3334749 TI - Detection of phosphorylated forms of Moloney murine leukemia virus major capsid protein p30 by immunoprecipitation and two-dimensional gel electrophoresis. AB - We detected phosphorylation of the major Moloney murine leukemia virus (M-MuLV) capsid polypeptide, p30, by using 32Pi-labeled virions. This was observed both on two-dimensional polyacrylamide gels directly or on one-dimensional gels of viral lysates that had been immunoprecipitated with monospecific goat anti-p30 serum. The phosphorylation event had been difficult to detect because pp12 the major virion phosphoprotein incorporates almost all of the 32P label added to infected cells (Y. Yoshinaka and R. B. Luftig, Virology 116:181-195, 1982). When immunoprecipitates from M-MuLV lysates labeled with 32Pi were compared with those labeled with [35S]methionine, it was calculated that the degree of phosphorylation at the p30 domain of Pr65gag was only 0.22 to 0.54% relative to phosphorylation at the p12 domain. Two-dimensional gel electrophoresis of the 32P labeled p30 immunoprecipitates showed that there were three phosphorylated p30 forms with isoelectric points (pIs) of 5.7, 5.8, and 6.0. These forms were generally more acidic than the [35S]methionine-labeled p30 forms, which had pIs of 6.0, 6.1, 6.3 (the major constituent with greater than 80% of the label), and 6.6. The predominant phosphoamino acid of the major phosphorylated p30 form (pI 5.8) was phosphoserine. Further, tryptic peptide analysis of this p30 form showed that only one peptide was predominantly phosphorylated. Based on a comparison of specific labeling of p30 tryptic peptides with [14C]serine, [35S]methionine, and 32Pi, we tentatively assigned the phosphorylation site to a 2.4-kilodalton NH2 terminal peptide containing triple tandem serines spanning the region from amino acids 4 to 24. PMID- 3334750 TI - Effects of 5'-terminal modifications on the biological activity of defective interfering RNAs of Sindbis virus. AB - We have been studying defective interfering (DI) genomes of the RNA enveloped virus Sindbis virus. Deletion mapping of a DI cDNA demonstrated that only sequences at the 3' and 5' termini of the genome are required for the DI RNA to be biologically active. We constructed a series of cDNAs that transcribe DI RNAs differing only in 5'-terminal sequences. Two of the 5' termini identical to ones found in naturally occurring DI RNAs are the 5' terminus of the virion RNA (DI 549) and the first 142 nucleotides from the 5' terminus of the subgenomic 26S mRNA attached to the 5' terminus of the virion RNA (DI-15). The latter has a 42 nucleotide deletion from nucleotides 25 to 66 in the 26S RNA sequence. These DI RNA transcripts were biologically active, but one (DI-526) which did not have the 42-nucleotide deletion of DI-15 was not replicated. The DI RNA isolated after the presumed amplification of the DI-526 transcript had deleted the first 54 nucleotides of the 26S RNA sequences. The 5' terminus of Sindbis virion RNA contains a stem and loop region that is conserved among alphaviruses. An 11 nucleotide deletion in DI-549 that disrupted this stem and loop rendered this DI RNA inactive. In contrast, this same deletion in DI-15 and one that removed an additional 100 nucleotides of the virion 5' terminus did not prevent its amplification. We did not detect by computer analysis any common secondary structures among the biologically active DI RNAs that distinguished them from those RNAs that were not amplified. Our results support the conclusion that tertiary structure or the ability of the RNA to adapt its structure upon interaction with protein is important in the recognition process. PMID- 3334752 TI - Senate committee sees NIH/DOE partnership in genome project. PMID- 3334753 TI - Balloon catheterization in infertility clinic. PMID- 3334755 TI - Lesbians call for greater physician awareness, sensitivity to improve patient care. PMID- 3334754 TI - Physicians turn to association libraries. PMID- 3334757 TI - Leads from the MMWR. Subtype of influenza A isolates--United States. PMID- 3334751 TI - Organization of the transcriptional control region of the E1b gene of adenovirus type 5. AB - Genetic analysis of the transcriptional control sequences of the E1b gene of adenovirus type 5 identified two regions that stimulated specific transcription by whole cell extracts from uninfected cells. The first region, located within 50 nucleotides (position -50) 5' to the transcription initiation (cap) site, contains a G+C-rich consensus-binding site (GC box) for the transcription factor Sp1 and a TATA box. Unambiguous stimulatory activity of the second region, between positions -358 and -127, was observed only in the absence of the GC box. DNase I protection experiments (footprinting) with crude nuclear extracts from uninfected cells revealed multiple DNA-protein interactions at the control region. Proximal to the initiation site, both the GC box and the cap site were protected; however, protection of the TATA box was not observed. In the distal region, four protein-binding sites, designated I through IV, were located between positions -250 and -120. Three of the four mapped in protein-coding sequences of the adjacent E1a gene. Sites I and II were 5' to position -218 whereas sites III and IV were 3' to position -218. This finding was consistent with results of the transcriptional analysis indicating that subsets of the distal region were sufficient for stimulation of transcription in vitro in the absence of the GC box. Within the boundaries of site I, a 10-base-pair protected sequence was similar to one located 5' to the adenovirus E1a, E2a, E3, E4, E2 late, and polypeptide IX transcription initiation sites. Sequences within the boundaries of the other three sites were similar to those within other viral and cellular enhancers. PMID- 3334756 TI - Addressing homosexuals' mental health problems. PMID- 3334758 TI - Leads from the MMWR. Human rabies despite treatment with rabies immune globulin and human diploid cell rabies vaccine--Thailand. PMID- 3334759 TI - Leads from the MMWR. Premature mortality in New Hampshire. PMID- 3334760 TI - Age as a risk factor for inadequate treatment. PMID- 3334761 TI - Immune serum globulin therapy for polymyositis. PMID- 3334762 TI - Radiation retinopathy. PMID- 3334763 TI - The resident by moonlight: a misguided missile. PMID- 3334765 TI - Cardiovascular risk factors and the adolescent. PMID- 3334764 TI - The quality of laboratory staff and the accuracy of results. PMID- 3334766 TI - Bulimia: when is a binge a binge? PMID- 3334767 TI - Push-up palmar palsy. PMID- 3334768 TI - Organic dust toxic syndrome. PMID- 3334769 TI - Thermography and xeromammography. PMID- 3334770 TI - Exercise and osteoporosis. PMID- 3334771 TI - The effectiveness of routine screening questions in the detection of alcoholism. AB - To assess the prevalence of alcoholism in an ambulatory medical clinic and to determine the effectiveness of screening questions for alcoholism, 232 new patients in a medical primary care unit were interviewed using a questionnaire that included the Michigan Alcoholism Screening Test (MAST). Based on MAST scores, 47 of 232 subjects were designated as alcoholics, yielding a prevalence of alcoholism of 20.3%. Sensitivities and specificities for alcohol-use questions were calculated using the MAST diagnosis of alcoholism. The questions "How much do you drink?" and "How often do you drink?" yielded low sensitivities of 34.0% and 46.8%, respectively. The question "Have you ever had a drinking problem?" considered alone had a high sensitivity of 70.2%; when combined with "When was your last drink?" this question had a sensitivity of 91.5%. We recommend the routine incorporation of these last two questions into the medical history in light of the high prevalence of alcoholism in this outpatient population. PMID- 3334772 TI - Risk of human immunodeficiency virus transmission from heterosexual adults with transfusion-associated infections. AB - The risk of human immunodeficiency virus (HIV) transmission was studied by interviewing and testing the serum of heterosexual contacts and casual family contacts of adults with transfusion-associated HIV infections. Two (8%) of 25 husbands and ten (18%) of 55 wives who had had sexual contact with infected spouses were seropositive for HIV. Compared with seronegative wives, the seropositive wives were older (median ages, 54 and 62 years; P = .08) and actually reported somewhat fewer sexual contacts with their infected husbands (means, 156 and 82; P greater than .1). There was no difference in the types of sexual contact or methods of contraception of the seropositive and seronegative spouses. There was no evidence of HIV transmission to the 63 other family members. Although most husbands and wives remained uninfected despite repeated sexual contact without protection, some acquired infection after only a few contacts. This is consistent with an as yet unexplained biologic variation in transmissibility or susceptibility. PMID- 3334773 TI - Oral contraceptives and cervical cancer risk in Costa Rica. Detection bias or causal association? AB - To examine the relationship between cervical cancer and oral contraceptive (OC) use, we analyzed data from a population-based, case-control study in Costa Rica. Women aged 25 to 58 years in whom cervical cancer was diagnosed and reported to the National Tumor Registry were examined as two separate case groups: invasive cervical cancer and carcinoma in situ (CIS). Controls were women aged 25 to 58 years identified through a national survey. Women who had used OCs had no increased risk of invasive cervical cancer compared with women who had never used OCs (relative risk, 0.8; 95% confidence interval, 0.5 to 1.3). Women who had used OCs had an increased risk of CIS compared with those who had never used OCs (relative risk, 1.6; 95% confidence interval, 1.2 to 2.2). However, further analyses indicated that this increased risk was confined to those who had recently used OCs. Also, the risk of CIS was not elevated in subgroups in which a history of cervical smears was not strongly linked to OC use. The elevated risk of CIS among OC users may therefore reflect a bias caused by enhanced detection of disease rather than a causal association. PMID- 3334774 TI - Implantation of a cardioverter/defibrillator without thoracotomy using a triple electrode system. AB - This article describes the implantation of an automatic implantable cardioverter/defibrillator in a 69-year-old man with coronary artery disease and recurrent sustained ventricular tachycardia without the need for a thoracotomy/sternotomy and epicardial electrodes. The patient underwent serial electrophysiological evaluation that revealed drug-refractory ventricular tachycardia. Surgical ablation was considered and rejected due to advanced, severe, pulmonary disease. A triple electrode system using two transvenous catheter electrodes and a submuscular patch electrode in the left midaxillary line was employed. A single shock was delivered simultaneously over two spatially distinct current pathways and reproducibly defibrillated ventricular fibrillation with energies less than or equal to 10 J. The automatic implantable cardioverter/defibrillator was implanted in the anterior abdominal wall and demonstrated reproducible termination of ventricular tachycardia and ventricular fibrillation. PMID- 3334775 TI - Bilateral optic neuropathy and osteolytic sinusitis. Complications of cocaine abuse. PMID- 3334776 TI - US Preventive Services Task Force. Automobile injury--selected risk factors and prevention in the health care setting. AB - Every year, highway crashes cause tens of thousands of deaths and millions of nonfatal injuries, many of which can be prevented. Following a mandate from the US Preventive Services Task Force, in this article we describe the magnitude of the automobile injury problem, identify injury risk factors that might be reduced by clinically based preventive programs, and review reports of interventions by health professionals to promote the use of child restraint devices, the only area in which we found published evaluations. We conclude that despite the lack of experimental evidence of the long-term effectiveness of clinically based efforts to promote occupant restraint use, such efforts may be warranted because of the enormous social and economic costs of automobile injury. In addition, physicians and other health professionals are urged to consider promoting nonclinical automobile injury prevention measures. PMID- 3334777 TI - Permanent injunction order against AMA. PMID- 3334778 TI - Statement from AMA's general counsel. PMID- 3334779 TI - RSNA index to imaging literature. 1985-1987. Radiological Society of North America. PMID- 3334780 TI - Cytogenetic analysis and response to ionizing radiations in a girl with severe muscular dystrophy. PMID- 3334782 TI - Discrimination of peripheral polyneuropathies caused by TTR variant or diabetes in the same pedigree through protein studies. PMID- 3334781 TI - Transthyretin (prealbumin) in familial amyloidotic polyneuropathy: genetic and functional aspects. PMID- 3334783 TI - Heterogeneity of Charcot-Marie-Tooth disease suggested by a linkage study. PMID- 3334784 TI - Purification and properties of short-chain acyl-CoA, medium-chain acyl-CoA, and isovaleryl-CoA dehydrogenases from human liver. PMID- 3334786 TI - Immunological and biochemical studies and pilot therapeutic trial with ubidecarenone in Kearns-Sayre patients. PMID- 3334787 TI - Employee immunizations: a comprehensive programmatic approach. PMID- 3334788 TI - Development of a model for precepting. The occupational health setting. PMID- 3334789 TI - The health of industrial workers in Poland. The nurse's contribution. PMID- 3334785 TI - Assay of acyl-CoA dehydrogenases in muscle and liver and identification of four new cases of medium-chain acyl-CoA dehydrogenase deficiency associated with systemic carnitine deficiency. PMID- 3334790 TI - Preparing grants: seeking funding for research proposals--Part I. PMID- 3334791 TI - AAOHN position statement--confidentiality of health information. PMID- 3334792 TI - AAOHN guidelines for confidentiality of health information. PMID- 3334793 TI - Record keeping. PMID- 3334794 TI - Conjunctival oxygen tension monitoring during a controlled phlebotomy. AB - A decrease in the conjunctival oxygen tension (Pcjo2) and conjunctival index (Pcjo2/Pao2) has been shown to be an early marker of acute blood loss. We sequentially measured Pcjo2, Pcjo2/Pao2, blood pressure, and pulse rate in five healthy adults after controlled phlebotomy of 450 mL and after intravenous fluid repletion. No significant changes occurred in either the Pcjo2 or Pcjo2/Pao2 after phlebotomy or after fluid replacement. We conclude that a blood loss of 450 mL in healthy, euvolemic adults is insufficient to perturb the conjunctival index. The lower limits of sensitivity of changes in Pcjo2 and Pcjo/Pao2 in response to acute blood loss remain to be established. PMID- 3334795 TI - Utilization and yield of drug screening in the emergency department. AB - Emergency qualitative tests for drugs are commonly ordered during evaluation of cases of suspected drug overdose. We prospectively compared the utilization and yield of drug screens based on urine and of identical tests of gastric contents under actual clinical conditions in a busy metropolitan emergency department. During the 4.5-month study period, physicians ordered drug screening in 405 of 582 (70%) study cases. Screens of both types of body fluid were ordered in only 95 cases (16%), suggesting study physicians regarded these tests to be functionally equivalent. Drug screens of gastric fluid were favored in cases involving acute ingestion and in medically complicated cases requiring gastric lavage. Urine drug screens were favored in clinically stable cases with primarily thought or behavior disorders. In the 95 cases for which both drug screens were ordered, gastric screens in 18 cases detected 20 drugs not detected by urine drug screening. Urine screening, on the other hand, identified 74 drugs not found on gastric screening in 48 cases. Gastric drug screening also performed poorly in comparison to quantitative serum drug levels. Seventeen false-positive urine or gastric screens were noted as well. Despite significant technical limitations, physicians frequently order drug screens in our emergency department. Qualitative drug screening of gastric fluid may prove useful in cases involving acute ingestion, but samples of urine and serum must also be submitted for analysis if optimal test performance is to be achieved. PMID- 3334796 TI - Echocardiographic diagnosis of acute pericardial effusion in penetrating chest trauma. AB - Pericardial tamponade persists as a diagnostic challenge to the clinician. The immediate diagnosis is particularly difficult when the patient is well compensated hemodynamically. In contrast to the deceptively stable appearance, the patient is at increased risk due to delayed onset, recognition, and therapy. A case of penetrating thoracic trauma is presented in which the concern about pericardial tamponade was considerable. However, the elements of clinical assessment were inconclusive. Two-dimensional echocardiography was employed in the emergency department to detect a pericardial effusion and thus avoid delayed management. Pericardial tamponade and associated vascular injuries were confirmed at surgery. PMID- 3334797 TI - Cellular telephone communication between hospitals and ambulances. AB - Cellular telephones provide a new means of wireless telephone communication. In an experimental design study comparing the clarity of receiving and transmitting communications with cellular telephones versus conventional emergency medical radio/microwave equipment, cellular telephones proved to be superior in all aspects of clarity and ease. Cellular telephones have numerous cost and equipment advantages over radio equipment and should replace conventional radio/microwave equipment for emergency medical communication in areas where reliable cellular telephone networks are available. This will improve an important facet of prehospital emergency care. PMID- 3334798 TI - Nasotracheal intubation in traumatic craniofacial dislocation: use of the lighted stylet. AB - The coexistence of facial trauma and suspected cervical spine injury represents a difficult problem in airway management. The successful use of guided nasotracheal intubation using a flexible lighted stylet is described, and its application to the critically injured patient is emphasized. PMID- 3334799 TI - Cases in electrocardiography. PMID- 3334800 TI - The uprooting of observational units from emergency departments: opportunity lost for emergency medicine? PMID- 3334801 TI - Scalp laceration repair without prior hair removal. AB - The effect on the infection rate of hair removal prior to scalp laceration repair has not been studied prospectively in the outpatient setting. Concern exists that not removing skin hair may lead to an increased incidence of serious wound infections. Sixty-eight scalp lacerations were repaired without hair removal and examined prospectively for infection. No infections were noted at 5-day follow up. The mean patient age was 21.8 +/- 19.8 years, and the mean laceration length was 2.5 +/- 2.0 cm. The mean time from injury to repair of laceration was 2.2 +/- 2.8 hours. Sixty-three lacerations (92.7%) were repaired within 3 hours of injury. A prospective, randomized study in a select patient population to examine the effect of prior hair removal on infection rate is warranted. PMID- 3334802 TI - Of pacing, patents, and patients. PMID- 3334803 TI - The role of hemoperfusion and hemodialysis in toxicology. PMID- 3334804 TI - A refinement of the emergency medicine filing system. PMID- 3334805 TI - Toxic smoke inhalation and aircraft fires. PMID- 3334806 TI - Field experience in aeromedical transport for an emergency medicine residency. PMID- 3334807 TI - Myocardial contusion without obvious severe chest trauma. PMID- 3334808 TI - Subungual hematoma. PMID- 3334809 TI - The legalization of heroin--a misguided effort. PMID- 3334810 TI - About our children. PMID- 3334811 TI - Delirium: diagnosis and management. PMID- 3334812 TI - AHA hospital hospice survey: key results. PMID- 3334813 TI - Creating primary caregivers where there are none. Tailoring hospice care to meet the needs of the community. PMID- 3334814 TI - Demographic profile of individuals with knowledge of the hospice concept. Who is more likely to use hospice services? PMID- 3334815 TI - Hospice administration. A life cycle model. PMID- 3334816 TI - The pathologic effects of photodynamic therapy on the larynx. Experimental study. AB - Using an argon pump dye laser at a wavelength of 630 nm, varying amounts of energy (10 to 170 J/cm2) were delivered to the presensitized (hematoporphyrin derivative) canine larynx. There appear to be four energy zones that result in progressive degrees of tissue response. Between 10 and 40 J/cm2 the larynx appears normal, with only mild erythema noted at 60 J/cm2. Above 100 J/cm2 moderate to severe erythema and edema were seen, with two upper-airway deaths observed. Transmission pattern analysis revealed that by either increasing the total energy applied and/or positioning the cylindrical diffuser tip at different levels of the larynx, the entire structure including the undersurface of the vocal cord and subglottic region could be exposed to red light. PMID- 3334817 TI - Anaplastic thyroid carcinoma. Association with differentiated thyroid cancer. AB - Fourteen cases of anaplastic thyroid carcinoma (ATC) treated at Baylor College of Medicine, Houston, during a 19-year period were reviewed. There was a 1.3:1 female preponderance, and the median patient age was 62 years. Ten (71%) of the anaplastic tumors either followed or occurred simultaneously with a well differentiated thyroid carcinoma. This finding adds support to the theory that ATC usually results from the transformation of well-differentiated thyroid carcinoma. A combination of surgery, radiation therapy, and chemotherapy was utilized for most patients. In this series of patients, the median duration of survival was four months following diagnosis, with only three patients (21%) alive at one year. Despite aggressive therapy, the prognosis for ATC remains poor. PMID- 3334818 TI - Uvulopalatopharyngoplasty in the sleep apnea syndrome. Predictors of results. AB - A prospective study of 34 consecutive patients with the sleep apnea syndrome was undertaken to evaluate the effectiveness and complications of, and predictors of, results in a conservative type of uvulopalatopharyngoplasty (UPPP). At six months, 65% of the patients had a 50% or greater reduction in the number of apneas and hypopneas per hour (responders). The responders to UPPP were less severely affected preoperatively regarding apneas and hypopneas, the mean number of which (+/- SD) were 32.7 +/- 20.8 compared with 64.6 +/- 26.0. They also had a lower body mass index before UPPP (31.3 +/- 4.1 vs 36.0 +/- 7.0 kg/m2). Preoperative computed tomography and cephalometry indicated that the nonresponders had narrower upper airways. It is concluded that UPPP is the treatment of choice for mild to moderate sleep apnea syndrome, but not for severely affected, heavily overweight patients with an increased tongue width. PMID- 3334819 TI - Ototoxicity of Vasocidin drops applied to the chinchilla middle ear. AB - Some widely used ototopical preparations are potentially toxic to the middle and inner ear. Vasocidin Ophthalmic Solution (sulfacetamide sodium and prednisolone sodium phosphate) has been advocated as an alternative agent that may have fewer toxic side effects in the treatment of otorrhea. Vasocidin was introduced into the bullae of nine chinchillas to investigate the effects on the middle and inner ear. The organ of Corti and stria vascularis were found to be entirely normal in 17 of the 18 temporal bones studied. Changes observed in the middle ears at one week included inflammation, hemorrhage, and effusion. Examination of specimens at four weeks revealed resolution of most of the inflammatory changes. The results of this experimental study indicate that Vasocidin causes reversible middle ear inflammation with little or no toxic effect on inner ear structures. PMID- 3334820 TI - Noninvasive imaging of the normal temporal bone. Comparison of sagittal surface coil magnetic imaging and high-resolution computed tomography. AB - High-resolution computed tomography (HRCT) is a noninvasive technique for evaluating the middle ear for primary and recurrent cholesteatoma. However, a limitation of HRCT is that it cannot differentiate between cholesteatoma and granulation tissue. Magnetic resonance imaging (MRI) is a noninvasive, nonradiologic technique that has been effective in demonstrating histochemical differences between various soft tissues. We present images from a normal living subject's temporal bone in the sagittal plane obtained with both HRCT and MRI. Anatomic correlates in the same cut planes are presented. The HRCT provided excellent detail of the bony landmarks within the temporal bone and was used as the reference for the MRI. The soft-tissue structures such as cranial nerves, cochlea, vestibule, and semicircular canals were identified. PMID- 3334821 TI - Nasal pharmacodynamics of brompheniramine in perennial rhinitis. AB - This study evaluated the relationship between brompheniramine maleate and changes in nasal reactivity. Ten subjects with moderate-to-severe perennial rhinitis took brompheniramine for seven days using either a standard formulation or sustained release preparation. Nasal aerodynamics and response to histamine were assessed at the end of the week. Despite varying doses of brompheniramine maleate (12 to 32 mg/d), there was no significant difference in nasal reactivity to histamine or in changes of nasal airflow, indicating that low doses of brompheniramine are highly effective in blocking histamine, receptors in the nasal mucosa. PMID- 3334822 TI - Use of the Kirschner wire for mandibular reconstruction. AB - An adaptation of the Kirschner wire, using tie wires for fixation of the Kirschner wire in primary mandibular reconstruction following ablative surgery, is described. Eighteen patients with a Kirschner wire serving as a prosthesis following mandibular resection were followed up. Except for three patients, who had extensive resection of the tongue, all patients were judged as having satisfactory mastication and deglutition. Only two patients required another operation for wire-related complications. The Kirschner wire, when modified as presented, proved a dependable and stable prosthesis for mandibular reconstruction. PMID- 3334823 TI - Surgery of the clivus and anterior cervical spine. AB - Traumatic, degenerative, benign, and malignant lesions of the clivus and cervical spine were treated by three basic surgical procedures. Midline skull base lesions in the nasopharynx, clivus, and C-1 were approached via the transmandibular and transcervical route. Lesions of C-2 and C-3 were operated on through a high transcervical route (above the hypoglossal nerve). A low transcervical route was used for lesions at the level of C-4 to C-7. PMID- 3334825 TI - Hearing recovery following suboccipital excision of acoustic neuroma. AB - Improvement of hearing after excision of an acoustic neuroma has been observed infrequently. We present a case of dramatic recovery of hearing in a patient with a 1-cm acoustic neuroma whose pure-tone thresholds and speech discrimination had profoundly deteriorated while she awaited surgical therapy. Postoperatively, her hearing in the affected ear is equal to that in her other ear, and her speech discrimination exceeds that of her best preoperative audiogram. Issues related to hearing preservation and improvement after acoustic tumor surgery are discussed. PMID- 3334826 TI - Actinomycosis otitis media. AB - Infection of the middle ear and mastoid by actinomycosis is uncommon. We report the 21st case in the English literature. Actinomycosis otitis media is characterized by an indolent course but may be fatal. Multiple recurrences after standard antibiotic therapy are common. Effective treatment consists of surgery and penicillin for several months. PMID- 3334824 TI - The precise midline forehead flap as a musculocutaneous flap. AB - The forerunners of the midline forehead flap date back to ancient India. The flap, as modified in this presentation, is often the treatment of choice for reconstructing significant full-thickness defects of the nose. The flap described is designed as a musculocutaneous flap incorporating skin, subcutaneous tissue, muscle, and aponeurosis. The enhanced vascularity of this flap allows precise thinning and tailoring at the distal end. A stepwise description of flap design is outlined. PMID- 3334827 TI - Midline granuloma due to illicit cocaine use. AB - The successful treatment of patients with midline granuloma requires prompt recognition of the cause as the therapy is quite specific. Nasal insufflation of cocaine is rarely mentioned as a cause. Two patients are described who used intranasal cocaine, leading to midline ulceration of the upper respiratory tract. PMID- 3334828 TI - Pathologic quiz case 2. Extramedullary plasmacytoma. PMID- 3334829 TI - Pathologic quiz case 1. Lingual osteoma. PMID- 3334830 TI - Nursing crisis issues to be addressed. PMID- 3334831 TI - How to survive nursing school. PMID- 3334832 TI - 12 innovative teaching strategies for psychiatric nursing. PMID- 3334833 TI - Mr. Benny just didn't care. PMID- 3334834 TI - Dying at home. PMID- 3334836 TI - Is ADN education choice or chance? PMID- 3334835 TI - Options ... nutrition educator. PMID- 3334837 TI - Articulation: a 2+2 nursing program success. PMID- 3334838 TI - Of nursing student recruitment: one program's approach. PMID- 3334839 TI - Spirit of nursing. PMID- 3334840 TI - The properties of brain galactocerebroside monolayers. AB - Using a Langmuir film balance we have compared the properties of films of the brain galactocerebrosides at 37 degrees C. There are two types of cerebroside in brain, those with an alpha-hydroxy substituent on the acyl chain (HFA) and those without (NFA). At equivalent pressures the areas of both cerebroside films are significantly less than the areas of films of the brain glycerolipids, the choline and ethanolamine phosphatides. The isotherm of NFA galactocerebrosides has two discontinuities, one at low and one at high film pressure, while the isotherm of HFA galactocerebrosides is a smooth curve at all film pressures. Below the high-pressure transition the area of the NFA film is significantly larger than the area of the HFA film. When compressed beyond the high-pressure transition there is a marked hysteresis between compression and expansion isotherms of the NFA galactocerebrosides. The pressures of both films continue to rise steeply when they are compressed into areas which are too small for them to exist as simple monolayers. We conclude that under compression cerebroside films form bilayer structures; that bilayer formation starts at low pressure and occurs progressively as the HFA cerebroside monolayer is compressed, but occurs more abruptly in the NFA cerebroside monolayer at the high-pressure-transition region of the isotherm. A study of pure cerebrosides with a single defined acyl chain shows that there is a correlation between the relative volumes of the hydrophobic and hydrophilic parts of the molecule and the ease of bilayer formation. The larger the relative volume of the hydrophilic group the more readily the cerebroside forms a bilayer film. Other brain lipids added to cerebroside monolayers have sharply differing effects on their areas. The areas of films containing cholesterol are less than the areas calculated by adding the areas of the pure components multiplied by their mole fractions. On the other hand, the area of phosphatidylcholine-containing films is much larger than calculated. PMID- 3334841 TI - Asymmetric orientation of the reconstituted aspartate/glutamate carrier from mitochondria. AB - A partially purified preparation of the aspartate/glutamate carrier from bovine heart mitochondria was reconstituted into liposomal membranes by chromatography on hydrophobic ion exchange resins. Based on the favorable conditions of this reconstituted system the transmembrane orientation of the inserted carrier protein could be determined by functional analysis. For reliable measurement of the reconstituted aspartate-glutamate exchange activity an optimized inhibitor stop technique using pyridoxal phosphate was developed. By simultaneous application of both forward and backward exchange experiments the practical usefulness of the reconstituted system could be extended to investigations including variation of internal and external substrate concentrations over a wide range. Thereby a complete set of Km values for both aspartate and glutamate at both the internal and external side of the proteoliposomes could be established. These experiments led to the following results and conclusions: (i) The observed substrate affinities are clearly different for the two different membrane sides both for aspartate (external 50 microM, internal 3 mM) and glutamate (external about 200 microM, internal 3 mM). (ii) The exclusive presence of only one type of transport affinity for every single substrate at one side of the liposomal membrane clearly demonstrates the asymmetric orientation of the functionally active carrier protein molecules. (iii) When comparing the values of these constants with published data obtained in mitochondria, an inside-out orientation of the aspartate/glutamate carrier after isolation and reinsertion into liposomes is strongly suggested. PMID- 3334842 TI - Surfactant-induced release of liposomal contents. A survey of methods and results. AB - A systematic approach to the phenomenon of surfactant-dependent release of liposomal contents has been attempted. A variety of methods have been comparatively studied. The influence of the size of the entrapped molecule, nature of the surfactant, composition of bilayers and sonication of liposomes have been considered separately. In order to compare different results, a parameter has been defined, R50, as the phospholipid/surfactant mole ratio producing 50% release of the entrapped solute. This parameter appears to be, to a large extent, independent of time and liposome concentration. Surfactant-induced release of liposomal contents does not occur as a result of breakdown of phospholipid bilayers, but is rather a different phenomenon, occurring at detergent concentrations substantially lower (2-5 times) than solubilization. The required amount of surfactant appears to increase with the size of the entrapped solute. R50 depends clearly on the nature of the soluble amphiphile, but there is no obvious relationship with its critical micellar concentration. Liberation of vesicle content also depends on bilayer composition: phospholipids have various effects on the stability of the membrane, while the hydrophobic peptide, gramicidin A, appears to have little influence. Cholesterol is interesting, since at equimolar proportions with phosphatidylcholine, it decreases the stability of bilayer towards Triton X-100, while increasing it in the presence of cholate. Sonication also exerts an influence on the surfactant-dependent release of vesicle contents; it appears to decrease the bilayer stability, so that lower detergent concentrations are required to liberate the entrapped solutes. Finally, it should be noted that, although the decrease in self-quenching of 6 carboxyfluorescein is a convenient method for the study of solute liberation, glucose release, as detected by enzymatic methods, may be more reliable for accurate measurements. PMID- 3334843 TI - Membrane damage by Cerebratulus lacteus cytolysin A-III. Effects of monovalent and divalent cations on A-III hemolytic activity. AB - The effects of monovalent and divalent cations on the hemolytic activity of Cerebratulus lacteus toxin A-III were studied. The activity of cytolysin A-III is remarkably increased in isotonic, low ionic strength buffer, the HC50 (the toxin concentration yielding 50% lysis of a 1% suspension of erythrocytes after 45 min at 37 degrees C) being shifted from 2 micrograms per ml in Tris or phosphate buffered saline to 20-30 ng per ml in sucrose or mannitol buffered with Hepes, corresponding to a 50-100-fold increase in potency. On the contrary, hemolytic activity decreases progressively as the monovalent cation concentration in the medium increases for Na+, K+, or choline salts. The divalent cations Ca2+ and Zn2+ likewise inhibit the cytolysin A-III activity, but more strongly than do the monovalent cations specified above. Zn2+ at a concentration of 0.3 mM totally abolishes both toxin A-III-dependent hemolysis of human erythrocytes and toxin induced leakage from liposomes. The observation of similar effects in both natural membranes and artificial bilayers suggests an effect of Zn2+ on the toxin A-III-induced membrane lesion, especially since Zn2+ does not alter binding of the cytolysin. The dose-response curve for toxin A-III exhibits positive cooperativity, with a Hill coefficient of 2 to 3. However, analysis of toxin molecular weight by analytical ultracentrifugation reveals no tendency to aggregate at protein concentrations up to 2 mg per ml. These data are consistent with a post-binding aggregational step which may be affected by the ionic strength of the medium. PMID- 3334844 TI - Dibasic amino acid interactions with Na+-independent transport system asc in horse erythrocytes. Kinetic evidence of functional and structural homology with Na+-dependent system ASC. AB - Amino acid transport in horse erythrocytes is regulated by three co-dominant allelomorphic genes coding for high-affinity transport activity (system asc1), low-affinity transport activity (system asc2) and transport-deficiency, respectively. The asc systems are selective for neutral amino acids of intermediate size, but unlike conventional system ASC, do not require Na+ for activity. In the present series of experiments we have used a combined kinetic and genetic approach to establish that dibasic amino acids are also asc substrates, systems asc1 and asc2 representing the only mediated routes of cationic amino acid transport in horse erythrocytes. Both transporters were found to exhibit a strong preference for dibasic amino acids compared with neutral amino acids of similar size. Apparent Km values (mM) for influx via system asc1 were L-lysine (9), L-ornithine (27), L-arginine (27), L-alanine (0.35). Corresponding Vmax estimates (mmol/l cells per h, 37 degrees C) were L-lysine (1.65), L-ornithine (2.15), L-arginine (0.54), L-alanine (1.69). Apparent Km values for L-lysine and L-ornithine influx via system asc2 were approximately 90 and greater than 100 mM, respectively, with Vmax values greater than 2 and greater than 1 mmol/l cells per h, respectively. Apparent Km and Vmax values for L-alanine uptake by system asc2 were 14 mM and 6.90 mmol/l cells per h. In contrast, L-arginine was transported by system asc2 with the same apparent Km as L-alanine (14 mM), but with a 77-fold lower Vmax. This dibasic amino acid was shown to cause cis- and trans-inhibition of system asc2 in a manner analogous to its interaction with system ASC, where the side-chain guanidinium group is considered to occupy the Na+-binding site on the transporter. Concentrations of extracellular L-arginine causing 50% inhibition of zero-trans L-alanine influx and half-maximum inhibition of L-alanine zero-trans efflux were 14 mM (extracellular L-alanine concentration 15 mM) and 3 mM (intracellular L-alanine concentration 15.5 mM), respectively. We interpret these observations as evidence of structural homology between the horse erythrocyte asc transporters and system ASC. Physiologically, intracellular L-arginine may function as an endogenous inhibitor of system asc2 activity. PMID- 3334845 TI - N-succinyldioleoylphosphatidylethanolamine: structural preferences in pure and mixed model membranes. AB - The structural preferences of the pH-sensitive phospholipid, N succinyldioleoylphosphatidylethanolamine (N-succinyl-DOPE), have been examined alone and in mixtures with DOPE by 31P-NMR, fluorescence energy transfer, and freeze-fracture techniques. The basic polymorphic behavior of pure N-succinyl DOPE and DOPE/N-succinyl-DOPE lipid systems and the influence of calcium and pH were investigated. It is shown that, similar to other negatively charged acidic phospholipids, N-succinyl-DOPE adopts the bilayer organization upon hydration. This structure is maintained at both pH 7.4 and 4.0 in the presence or absence of calcium. In the mixed lipid system, N-succinyl-DOPE can stabilize the non-bilayer lipid, DOPE, into a bilayer structure at both pH 7.4 and 4.0 at more than 10 mol% N-succinyl-DOPE, although a narrow 31P-NMR lineshape is observed at acidic pH values. This corresponds to the presence of smaller vesicles as shown by quasi elastic light scattering measurements. Addition of equimolar calcium (with respect to N-succinyl-DOPE) to the DOPE/N-succinyl-DOPE systems induces the hexagonal HII phase at both pH values. In unilamellar systems with similar lipid composition the addition of Ca2+ results in membrane fusion as indicated by fluorescence energy-transfer experiments. These findings are discussed with regard to the molecular mechanism of the bilayer to hexagonal HII phase transition and membrane fusion and the utility of N-succinyl-DOPE containing pH sensitive vesicles as drug-delivery vehicles. PMID- 3334846 TI - Recovery of Dunaliella salina cells following hydrogenation of lipids in specific membranes by a homogeneous palladium catalyst. AB - Unsaturated fatty acyl chains of Dunaliella salina membrane lipids can be catalytically reduced by the homogeneous hydrogenation catalyst palladium di(sodium alizarine monosulphonate), Pd(QS)2, under conditions permitting full recovery of the cells within 24 h. The hydrogenation is accomplished by incubation of cells with the hydride form of Pd(QS)2 under 1 atmosphere of H2 and for 2 min or less. Following this protocol, hydrogenation reduces only those fatty acids located in the plasma membrane and other membranes located near the cell surface. The limited reactivity in vivo is due to the fact the Pd(QS)2 permeates into the living cells more slowly than it does into liposomes prepared from extracted Dunaliella membrane lipids. While Dunaliella is completely unaffected by exposure to the oxygenated, inactive catalyst, hydrogenated cells cease growth for approximately 12 h, during which time the hydrogenated acyl chains are being enzymatically retroconverted to their original unsaturated form. When the lipid composition approaches its prehydrogenation values, growth resumes, presumably due to the restoration of normal membrane functions. The system shows promise for studying the metabolic regulation of membrane microviscosity. PMID- 3334847 TI - A new family of dispersed, highly repetitive sequences in bovine genome. AB - A new family of highly repetitive sequences which are dispersed in bovine genome is described. The members of the family are visible on agarose or polyacrylamide gels as a diffused band about 510 bp in length arising after digestion with PstI restriction nuclease. This family of fragments comprises the 160 bp bovine Bsu family and is linked with bovine Alu-like sequences. PMID- 3334848 TI - Characterization of the fluorescence of the antitumor agent, mitoxantrone. AB - Studies have been conducted on the absorption, fluorescence excitation and fluorescence emission of mitoxantrone, an important antineoplastic agent. Mitoxantrone has been found to fluoresce with excitation maxima at 610 and 660 nm and emission maximum at 685 nm. Further characterizations of the fluorescence were undertaken to study its usefulness in biological studies. Mitoxantrone fluorescence intensity is altered by pH and the emission spectrum is red-shifted by DNA. Furthermore, the fluorescence polarization is enhanced by DNA, confirming the binding of the antitumor agent to DNA. The fluorescence spectra are slightly modified by changes in ionic strength and the addition of albumin. Data establishing the usefulness of fluorescence to measure serum concentrations in the range of 0.0 to 100 nM are presented. Such determinations can distinguish serum mitoxantrone from its non-fluorescent primary metabolite. PMID- 3334849 TI - Kinetics of replicon initiation during S phase of Chinese hamster ovary cells. AB - Chinese hamster ovary (CHO) cells were synchronized by a thymidine-hydroxyurea block. At different times after release from the block, cells were treated with trioxsalen and long-wavelength ultraviolet light to crosslink DNA in vivo and were labelled with [3H]thymidine for 30 min. This technique permits labelling of only the short nescent DNA fragments initiated between crosslinks. The amount of radioactivity incorporated in these fragments during the labelling period reflects the number of replicon initiation events and allows us to follow the replicon initiation pattern after removing the inhibitor. It was shown that the rate of initiation was high at the beginning of S phase and then steadily decreased. PMID- 3334850 TI - Molecular cloning and nucleotide sequence of tuna growth hormone cDNA. AB - cDNA for mRNA of tuna growth hormone (GH) was cloned by screening a cDNA library constructed from tuna pituitary gland poly(A)+ RNA. The nucleotide sequence of cDNA (911 bases) revealed an open reading frame of 615 nucleotides, including a sequence (51 bases) for a possible secretory protein leader peptide. Noncoding regions were found in the nucleotide sequences up- (5'-terminal: 65 bases) and down- (3'-terminal: 231 bases) stream of the open reading frame. An amino-acid sequence deduced from the nucleotide sequence of the cDNA was identical with that determined in the purified tuna GH. Tuna GH was composed of 187 amino acids, and had a calculated molecular weight of 21,275. Amino-acid sequencing showed that there was one possible N-glycosylation site at Asn (Asn-Cys-Thr). Tuna GH showed amino-acid sequence homologies with chum salmon (67%), yellow tail (90%) and with human (32%) growth hormones. PMID- 3334851 TI - Expression of transfected human CuZn superoxide dismutase gene in mouse L cells and NS20Y neuroblastoma cells induces enhancement of glutathione peroxidase activity. AB - The human CuZn superoxide dismutase (superoxide dismutase 1) a key enzyme in the metabolism of oxygen free-radicals, is encoded by a gene located on chromosome 21 in the region 21 q 22.1 known to be involved in Down's syndrome. A gene dosage effect for this enzyme has been reported in trisomy 21. To assess the biological consequences of superoxide dismutase 1 overproduction within cells, the human superoxide dismutase 1 gene and a human superoxide dismutase 1 cDNA were introduced into mouse L cells and NS20Y neuroblastoma cells. Both cell types expressed elevated levels (up to 3-fold) of enzymatically active human superoxide dismutase 1. These human superoxide dismutase 1 overproducers, especially neuronal cell lines, showed an increased activity in the selenodependent glutathione peroxidase. These data are consistent with the possibility that gene dosage of superoxide dismutase 1 contributes to oxygen metabolism modifications previously described in Down's syndrome. PMID- 3334852 TI - Binding site of alpha 2-plasmin inhibitor to plasminogen. AB - Peptide T-11, a carboxyl terminal tryptic fragment of alpha 2-plasmin inhibitor, inhibits the reversible first step of the reaction between plasmin and alpha 2 plasmin inhibitor. To elucidate which amino-acid residues played a important role in the inhibitory activity of peptide T-11, we prepared the various synthetic derivatives of peptide T-11 and determined the peptide concentration that inhibited the apparent rate constant of the reaction between plasmin and alpha 2 plasmin inhibitor by 50% (IC50). Peptide III, which lacked the residues Gly-1 to Pro-7 of peptide I (peptide T-11), had a strong inhibitory activity, like peptide I (IC50: peptide I, 7 microM; peptide III, 13 microM). The peptides that lacked the Leu-9 and Lys-10 or Lys-26 of peptide III showed much weaker activity, and the loss or amidation of the C-terminal lysine of peptide III also markedly reduced the inhibitory activity. Peptide III competitively inhibited the binding of [14C]tranexamic acid to kringle 1 + 2 + 3 (K1-3) and kringle 4 (K4) in a binding assay performed by the gel-diffusion method. The respective dissociation constants (Kd) of peptide III for K1-3 and K4 were 0.85 microM and 35.2 microM. These data suggest that the amino residue of Lys-10 and the carboxylic acid of Lys-26 in peptide T-11 play crucial roles in the ionic binding of alpha 2-plasmin inhibitor to the tranexamic acid-binding site (lysine-binding site) of plasminogen. Peptide T-11: H-G-D-K-L-F-G-P-D-L-K-L-V-P-P-M-E-E-D-Y-P-Q-F-G-S-P-K OH. PMID- 3334853 TI - Low-frequency dielectric properties of lysozyme as a function of hydration and pH of lyophilisation. AB - Dielectric measurements have been made on lysozyme-compressed powders as a function of hydration and of the pH at which the samples were lyophilised. A dielectric dispersion previously described in the literature and known as the alpha-dispersion is found to be strongly influenced by the lyophilisation pH, and reaches a maximum magnitude at around pH 11. A dielectric loss of the form of the alpha-dispersion is observed in polylysine hydrobromide and the sodium salt of polyglutamic acid, but not for polyglycine. These results can be understood in terms of proton transfer between the ionisable side-groups, as well as by the controlling influence of counter-ions in moderating the energetics of the proton transfer processes. Another, weaker and hitherto unreported, dielectric loss process has been found for lysozyme, polyglycine, polylysine and poly(glutamic acid). This is referred to as the alpha 2-dispersion and its characteristics can be understood in terms of vibrational motions of the polypeptide backbones and the plasticising action of bound water. PMID- 3334854 TI - Interaction of parvalbumin of pike II with calcium and terbium ions. AB - Fluorimetric titrations of parvalbumin II (pI 4.2) of pike (Pike II) with Ca2+ and Tb3+ show the CD and EF binding sites to be non-equivalent. The intrinsic binding constants of the strong and the weak sites obtained for Ca2+ are: KsCa = 1.6.10(8) M-1; KwCa = 6.6.10(5) M-1. Differences of the order of 100% were encountered between the Tb3+ binding constants obtained with four different versions of titration. Their average values are: KsTb = 1.9.10(11) M-1; KwTb = 1.0.10(7) M-1. The distances of the strong and the weak sites from the singular Tyr-48, rs = 9.5 A and r2 = 11.5 A, were derived from Forster-type energy transfer and proved compatible with the X-ray structure of parvalbumin III (pI 4.2) of carp (CarpIII). From the distances, it is suggested that CD is the strong and EF the weak metal-binding site of PikeII. Tb3+ was shown by CD spectroscopy to have the same structural effect on PikeII as Ca2+. Removal of the metal ions from PikeII results in a decrease of helix content as monitored by CD spectroscopy. This decrease is larger than that in CarpIII. A concomitant decrease of the fluorescence quantum yield at nearly constant decay time is indicative of mainly static quenching, probably by the non-coordinating carboxylate groups. The maximum helix content is almost completely reestablished upon binding of the first metal ion. However, small changes of the energy transfer in PikeII with one terbium ion bound to the strong site indicate fine structural rearrangements of the strong binding site when Ca2+ is bound to the weak one. PMID- 3334855 TI - A kinetic study of the reactions between H2O2 and Cu,Zn superoxide dismutase; evidence for an electrostatic control of the reaction rate. AB - H2O2 was shown to reduce the copper ion of native bovine Cu,Zn superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) (ECu2+) and to oxidize the reduced enzyme (ECu+). The time-course of these processes was monitored by NMR measurement of the longitudinal relaxation rate of the water protons. A steady-state characterized by the same ratio [ECu2+]/[( EC2+] + [ECu+]) was obtained either by starting from the oxidized or the reduced enzyme. The kinetics of these processes appear to be quite complex, since different reactions between H2O2, or its reaction products, and the enzyme-bound copper control the reaction rate. The solution of the differential equations describing the kinetic processes showed that the oxidation and the reduction of the copper ion by H2O2 are first-order with respect to the copper ion itself only when these processes approach the steady-state. The rate constants of the reduction and oxidation reactions were calculated according to these equations and were found to have comparable values which are in the range 5-80 and 5-45 M-1.min-1, respectively, changing the pH from 5.6 to 7 at 0.21 M ionic strength. This result, together with the dependence of the reaction rates on pH and ionic strength, points to HO2- as the reactive species in both processes, and indicates that the electrostatic control of the access of the peroxide to the active site is the rate-determining step of the two redox reactions. PMID- 3334856 TI - Heteromerous interactions among glycolytic enzymes and of glycolytic enzymes with F-actin: effects of poly(ethylene glycol). AB - Interactions of glucose-6-phosphate isomerase (D-glucose-6-phosphate ketol isomerase, EC 5.3.1.9), aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3 phosphate lyase, EC 4.1.2.13), glyceraldehyde-3-phosphate dehydrogenase (D glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12), triose-phosphate isomerase (D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1), phosphoglycerate mutase (D-phosphoglycerate 2,3-phosphomutase, EC 5.4.2.1), phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1 phosphotransferase, EC 2.7.3), enolase (2-phospho-D-glycerate hydro-lyase, EC 4.2.1.11), pyruvate kinase (ATP:Pyruvate O2-phosphotransferase, EC 2.7.1.40) and lactate dehydrogenase [S)-lactate:NAD+ oxidoreductase, EC 1.1.1.27) with F-actin, among the glycolytic enzymes listed above, and with phosphofructokinase (ATP:D fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) were studied in the presence of poly(ethylene glycol). Both purified rabbit muscle enzymes and rabbit muscle myogen, a high-speed supernatant fraction containing the glycolytic enzymes, were used to study enzyme-F-actin interactions. Following ultracentrifugation, F-actin and poly(ethylene glycol) tended to increase and KCl to decrease the pelleting of enzymes. In general, the greater part of the pelleting occurred in the presence of both F-actin and poly(ethylene glycol) and the absence of KCl. Enzymes that pelleted more in myogen preparations than as individual purified enzymes in the presence of poly(ethylene glycol) and the absence of F-actin were tested for specific enzyme-enzyme associations, several of which were observed. Such interactions support the view that the internal cell structure is composed of proteins that interact with one another to form the microtrabecular lattice. PMID- 3334857 TI - Acyl-CoA synthetase activity in Plasmodium knowlesi-infected erythrocytes displays peculiar substrate specificities. AB - In its blood stages the malaria parasite, Plasmodium, displays very high lipid metabolism. We present evidence for an abundant long-chain acyl-CoA synthetase (EC 6.2.1.3) activity in Plasmodium knowlesi-infected simian erythrocytes. The activity was found to be 20-fold higher in the schizont-infected (the last parasite stage) than in control erythrocytes. The cosubstrate requirements of the enzyme were similar to those previously reported for acyl-CoA synthetases from other sources. Among the separated reaction products of oleyl-CoA synthetase, only PPi and oleyl-CoA were inhibitory, with Ki over 350 microM. The fatty acid specificity of the parasite acyl-CoA synthetase activity was fairly marked and depended on the unsaturation state of the substrate. The tested fatty acids displayed similar Vmax, whereas their Km ranged from 11 (palmitate) to 59 microM (arachidonate). Finally, experiments involving heat inactivation and separation on hydroxyapatite excluded the presence of a specific arachidonyl-CoA synthetase identical to those present in other cells. On the other hand, fatty acid competition experiments evidenced the existence of at least two distinct enzymatic sites for fatty acid activation in P. knowlesi-infected simian erythrocytes: one is specific for saturated fatty acids and the other for polyunsaturated species, whereas oleate could be activated at both sites. PMID- 3334858 TI - Vesicular cholesterol in bile. Relationship to protein concentration and nucleation time. AB - A study was done to determine whether the nucleation time was related to the amount of cholesterol carried in vesicles. Bile was obtained from cholesterol gallstone patients and controls. Gel-exclusion chromatography was used to separate vesicles and micelles in the native bile using an eluting buffer containing 10 mM sodium cholate. The percent of total cholesterol carried in vesicles in gallbladder bile of stone patients was significantly greater than that in control patients. Total cholesterol concentration in gallbladder bile of stone patients was significantly greater than in controls. This difference was due to the fact that vesicular cholesterol concentration was significantly greater in the gallbladder bile of stone patients compared to controls. Micellar cholesterol concentrations were similar in the two groups. Nucleation time was related significantly to vesicular cholesterol concentration in correlation analysis and, as previously shown, so was total protein concentration. This study supports the importance of vesicular cholesterol in solid crystal formation and demonstrates for the first time that the rate of cholesterol monohydrate crystal formation is directly related to the amount of cholesterol transported in vesicles. PMID- 3334859 TI - The stimulation of arachidonic acid metabolism in human platelets by hydrodynamic stresses. AB - Even though shear-induced platelet activation and aggregation have been studied for about 20 years, there remains some controversy concerning the arachidonic acid metabolites formed during stress activation and the role of thromboxane A2 in shear-induced platelet aggregation. In this study, platelets were labelled with [1-14C]arachidonic acid to follow the metabolism of arachidonic acid in stimulated platelets using HPLC and scintillation counting. Platelets activated by thrombin formed principally thromboxane A2, 12-hydroxy-5,8,10 heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12 HETE). In contrast, for platelets activated by shear--though arachidonic acid metabolism was stimulated--only 12-HETE was formed and essentially no cyclooxygenase metabolites were detected. This indicates that physical forces may initiate a different pathway for eicosanoid metabolism than most commonly used chemical stimuli and perhaps also implies that regulation of the cyclooxygenase activity may be a secondary level of regulation in eicosanoid metabolism. PMID- 3334860 TI - Preferential hydrolysis of peroxidized phospholipid by lysosomal phospholipase C. AB - The susceptibility of partially peroxidized liposomes of 2-[1-14C] linoleoylphosphatidylethanolamine ([14C]PE) to hydrolysis by cellular phospholipases was examined. [14C]PE was peroxidized by exposure to air at 37 degrees C, resulting in the formation of more polar derivatives, as determined by thin-layer chromatographic analysis. Hydrolysis of these partially peroxidized liposomes by lysosomal phospholipase C associated with cardiac sarcoplasmic reticulum, and by rat liver lysosomal phospholipase C, was greater than hydrolysis of non-peroxidized liposomes. By contrast, hydrolysis of liposomes by purified human synovial fluid phospholipase A2 or bacterial phospholipase C was almost completely inhibited by partial peroxidation of PE. Lysosomal phospholipase C preferentially hydrolyzed the peroxidized component of the lipid substrate which had accumulated during autoxidation. The major product recovered under these conditions was 2-monoacylglycerol, indicating sequential degradation by phospholipase C and diacylglycerol lipase. Liposomes peroxidized at pH 7.0 were more susceptible to hydrolysis by lysosomal phospholipases C than were liposomes peroxidized at pH 5.0, in spite of greater production of polar lipid after peroxidation at pH 5.0. Sodium bisulfite, an antioxidant and an inhibitor of lysosomal phospholipases, prevented: (1) lipid autoxidation, (2) hydrolysis of both non-peroxidized and peroxidized liposomes by sarcoplasmic reticulum and (3) loss of lipid phosphorus from endogenous lipids when sarcoplasmic reticulum was incubated at pH 5.0. These studies show that lipid peroxidation may modulate the susceptibility of phospholipid to attack by specific phospholipases, and may therefore be an important determinant in membrane dysfunction during injury. Preservation of membrane structural and functional integrity by antioxidants may result from inhibition of lipid peroxidation, which in turn may modulate cellular phospholipase activity. PMID- 3334861 TI - Diacylglycerol acyltransferase in maturing safflower seeds: its influences on the fatty acid composition of triacylglycerol and on the rate of triacylglycerol synthesis. AB - Diacylglycerol acyltransferase in a particulate preparation from maturing safflower seeds showed no strict selectivity for acyl-CoA when acyl-CoA substrates were administered as mixtures. This suggested that the fatty acid composition of position 3 in safflower triacyl-sn-glycerol exclusively depends on the acyl-CoA composition in the cell. The specific activity of the acylation was approximately 3 nmol/min per mg protein of the preparation under the optimum assay conditions. This low activity and other data appeared to indicate that the diacylglycerol acyltransferase reaction may be the rate-limiting step in triacylglycerol synthesis in vivo. PMID- 3334862 TI - Pyrene dodecanoic acid coenzyme A ester: peroxisomal oxidation and chain shortening. AB - Pyrenedodecanoyl-CoA was beta-oxidized by isolated rat liver peroxisomes at a rate which was about 50% of that observed with palmitoyl-CoA. Measurement of the quantity of NADH formed from a limiting amount of pyrenedodecanoyl-CoA suggested that it was subjected to two to three cycles of beta-oxidation. Pyrenedodecanoyl CoA was a very poor substrate for carnitine palmitoyltransferase, exhibiting less than 1% of the rate obtained with palmitoyl-CoA; it also was a strong inhibitor of this enzyme. With rat liver microsomal alpha-glycerophosphate acyltransferase the rate of reaction with pyrenedodecanoyl-CoA was only 3-4% of that observed with palmitoyl-CoA. PMID- 3334863 TI - Different reactivities of monoclonal antibodies to ganglioside lactones. AB - Six murine monoclonal antibodies were found to react with ganglioside GD2 lactone as well as purified ganglioside GD2. However, the reactivities of these antibodies to various ganglioside lactones were found to differ from each other. Four antibodies only reacted with GD2 lactones, while the other two cross-reacted with lactones of other gangliosides such as GD1b and GT1b. PMID- 3334864 TI - Fatty acid desaturation in the intestinal mucosa. AB - Information as to the ability of the enterocyte to desaturate fatty acids is lacking. This is important in understanding whether the source of intestinal arachidonic (20:4(n-6) acid is biliary or from de novo synthesis. Delta 9- and delta 6-desaturase enzymes were assayed in homogenates of rat jejunum, ileum and liver. Rat small intestine possesses desaturase activity to convert palmitic (16:0) to palmitoleic (16:1) and linoleic (18:2(n-6) to linolenic (18:3(n-6) acid. Enzyme activities were highest in liver relative to activity in jejunal and ileal homogenates. It is concluded that delta 9- and delta 6-desaturase activities may have an important role in determining physico-chemical properties and thus transport properties of enterocyte membranes. PMID- 3334865 TI - Interaction of alpha-tocopherol with iron: antioxidant and prooxidant effects of alpha-tocopherol in the oxidation of lipids in aqueous dispersions in the presence of iron. AB - The dual functions of alpha-tocopherol in the oxidation of lipids in aqueous dispersions in the presence of iron were studied, aiming specifically at elucidating the effect of interaction between alpha-tocopherol and iron. Ferrous ion decomposed hydroperoxide rapidly and induced the free radical chain oxidation of soybean phosphatidylcholine liposomes. alpha-Tocopherol acted primarily as a radical scavenger in the oxidation induced by ferrous ion and acted as an antioxidant. Ferric ion decomposed hydroperoxide much more slowly than ferrous ion, but it also induced the oxidation of liposomal membranes. alpha-Tocopherol incorporated into artificial liposomal membranes reduced ferric ion rapidly to give more reactive ferrous ion, and alpha-tocopherol acted either as an antioxidant or as a prooxidant depending on the experimental conditions. When alpha-tocopherol was depleted by the interaction with ferric ion, it acted solely as a prooxidant, whereas if some alpha-tocopherol remained, it acted as an antioxidant. On the other hand, alpha-tocopherol residing in the intact erythrocyte membranes did not reduce ferric ion in the aqueous region. PMID- 3334866 TI - Activities of some enzymes of phospholipid metabolism in cultured rat ventricular myocytes in normoxic and hypoxic conditions. AB - Phospholipid catabolism is thought to be one of the critical events in membrane injury during heart ischemia. In this work, the enzymes involved in phospholipid metabolism were studied in purified cultured ventricular myocytes in normoxic and hypoxic conditions. Purified ventricular myocytes exhibited an alkaline phospholipase A activity which had sn-2 specificity and which was calcium dependent, and an acid phospholipase A activity with sn-1 specificity. These cells also exhibited lysophospholipase and acyl-CoA/lysophosphatidylcholine acyltransferase activities. Oxygen deprivation of the myocardial cells for 4 h resulted in a sharp reduction of both phospholipase A2 and A1 activities. The activities of the other lipolytic enzymes were unaffected by hypoxia. Although hypoxia resulted in a marked increase of lactate dehydrogenase leakage in the bathing fluid, no additional release of the lipolytic enzymes and mitochondrial enzyme was observed. However, we noted an important alkaline phospholipase A2 leakage during normoxia. It is suggested that ventricular myocytes, under hypoxia, tend to prevent phospholipid degradation by reducing their phospholipase A activities. PMID- 3334867 TI - Free fatty acids: a stimulus for mucin hypersecretion in cholesterol gallstone biles. AB - The concentration of free fatty acids, phosphatidylcholine and lysophosphatidylcholine, and the fatty acid composition as well as the levels of the mucins, analyzed by an improved GLC method, were examined in ten biles from patients with cholesterol gallstones (pathological biles) and in ten control biles. In pathological biles the amounts of free fatty acids and phosphatidylcholine, were significantly higher (8.99 +/- 1.09) vs. 2.75 +/- 0.62 micrograms/mg) and lower (6.62 +/- 0.71 vs. 21.91 +/- 3.86 micrograms/mg), respectively, than in control biles, indicating that a relationship exists between the two lipid fractions. Lysophosphatidylcholine concentrations remained unchanged in the two groups (1.02 +/- 0.55 micrograms/mg in pathological biles vs. 1.32 +/- 0.57 micrograms/mg in control biles). The increased levels of free fatty acids were directly correlated (r = 0.73, P less than 0.05) with biliary hypersecretion of mucus glycoproteins. Acetylglucosamine and acetylgalactosamine were significantly higher in pathological biles than in control biles (1.91 +/- 0.67 vs. 0.60 +/- 0.13 microgram/mg). The nucleating potency of the increased amounts of mucins, coupled with lowered levels of phosphatidylcholine, might play a very important role in stone formation and precipitation. PMID- 3334869 TI - Uptake of HDL unesterified and esterified cholesterol by human endothelial cells. Modulation by HDL phospholipolysis and cell cholesterol content. AB - Human HDL (1.070-1.210), doubly labelled with 3H/14C-labelled unesterified cholesterol and 3H-labelled esterified cholesterol were incubated for 1-5 h with monolayer cultures of human endothelial cells. HDL were preincubated for 60-120 min the presence of albumin and with/without purified phospholipase A2 (control HDL, phospholipase A2 HDL) before dilution in the cell culture medium. Average phosphatidylcholine (PC) degradation was 62.10% +/- 2.57% (range 45-80%). A purified lipase/phospholipase A1 from guinea pig pancreas was used in some experiments (range of PC hydrolysis: 16-70%). (1) 3H/14C-labelled unesterified cholesterol and 3H-labelled esterified cholesterol appeared in cells during 0-5 h incubations. Trypsin treatment allowed a simple adsorption of HDL onto the cell surface to be avoided, and most of the 3H-labelled esterified cholesterol transferred to cells was hydrolysed. Cell uptake of radioactive cholesterol increased as a function of HDL concentration but no saturation was achieved at the highest lipoprotein concentration used (200 micrograms cholesterol/ml). Flux of 3H/14C-labelled unesterified cholesterol was related to the cell cholesterol content, suggesting that it might partly represent an exchange process. The cell cholesterol content was slightly increased after 5 h incubation with HDL (+16%). (2) Pretreatment of HDL with purified phospholipase A2 doubled on average the amount of cell recovered 3H-labelled esterified cholesterol, while the flux of 3H/14C-labelled unesterified cholesterol was enhanced by 15-25%. Both transfer and cell hydrolysis of 3H-labelled esterified cholesterol were increased. A stimulation was also observed using purified lipase/phospholipase A1, provided that a threshold phospholipid degradation was achieved (between 27 and 45%). (3) Endothelial cells were conditioned in different media so as to modulate their charge in cholesterol. The uptake of 3H-labelled esterified cholesterol was found to be significantly higher in cholesterol-enriched cells compared to the sterol depleted state. Finally, movements of 3H-labelled esterified cholesterol from HDL to endothelial cells were essentially unaffected by cell density or by the presence of partially purified cholesterol ester transfer protein. The possible roles of the transfer of HDL esterified cholesterol to endothelial cells and its modulation by phospholipases are discussed. PMID- 3334868 TI - Regulation of fetal lung disaturated phosphatidylcholine synthesis by de novo palmitate supply. AB - Lung surfactant disaturated phosphatidylcholine (PC) is highly dependent on the supply of palmitate as a source of fatty acid. The purpose of this study was to investigate the importance of de novo fatty acid synthesis in the regulation of disaturated PC production during late prenatal lung development. Choline incorporation into disaturated PC and the rate of de novo fatty acid synthesis was determined by the relative incorporation of [14C]choline and 3H2O, respectively, in 20-day-old fetal rat lung explants and in 18-day-old explants which were cultured 2 days. Addition of exogenous palmitate (0.15 mM) increased (26%) choline incorporation into disaturated PC but did not inhibit de novo fatty acid synthesis, as classically seen in other lipogenic tissue. Even in the presence of exogenous palmitate, de novo synthesis accounted for 87% of the acyl groups for disaturated PC. Inhibition of fatty acid synthesis by agaric acid or levo-hydroxycitrate decreased the rate of choline incorporation into disaturated PC. When explants were subjected to both exogenous palmitate and 60% inhibition of de novo synthesis, disaturated PC synthesis was below control values and 75% of disaturated PC acyl moieties were still provided by de novo synthesis. These data show that surfactant disaturated PC synthesis is highly dependent on the supply of palmitate from de novo fatty acid synthesis. PMID- 3334870 TI - A dexamethasone-induced protein stimulates delta 9-desaturase activity in rat liver microsomes. AB - The effect of dexamethasone on the oxidative desaturation of [1-14C]palmitic to palmitoleic acid on rat liver microsomes, was studied. After 12 h of dexamethasone injection (1 mg/rat) a significant increase in delta 9-desaturase activity, was observed. This effect was also produced by a factor present in a 110,000 X g supernatant soluble fraction obtained after washing crude microsomes from dexamethasone-treated rats with a low ionic strength solution. The dexamethasone-induced factor was present not only in the liver cytosolic fraction of treated animals but also in the cytosol of isolated HTC cells previously incubated with the hormone. Dexamethasone would act via a newly synthesized modulatory factor. The effect depends on an unchanged protein structure, since its biological activity is impaired by trypsin digestion. PMID- 3334871 TI - Flow kinetics of nylon open-tubular and beaded immobilized glucose oxidase reactors. AB - Equations describing the flow kinetics of immobilized glucose oxidase in open nylon tubes and in tubes filled with solid glass spheres were experimentally determined. Reactors of three different tube (dt) and bead (db) diameters were tested using various linear flow rates (vf) and glucose concentrations ([S]). The kinetics of the open-tubular reactors were described by [P] = 1.5.10(-3) [S] L0.86 vf-0.78 dt-0.9 and the kinetics of the beaded-tubular reactors by [P] = 5.10(-3) [S] L0.98 vf-0.75 dt-1.0 (db/dt)2.7, where [P] equals the concentration of H2O2 formed. The aspect ratio, db/dt, is the critical design factor for beaded reactors. PMID- 3334872 TI - Purification and characterization of the isozymes of phosphoenolpyruvate carboxykinase from rabbit liver. AB - Procedures are described for the purification of the mitochondrial and cytosolic isozymes of phosphoenolpyruvate carboxykinase from rabbit liver. Examination of the purified isozymes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated apparent homogeneity and identical molecular weights of approximately 65,000. Gel filtration chromatography of the native isozymes, however, yielded apparent molecular weights of 68,000 and 56,000 for the cytosolic and mitochondrial isozymes, respectively. The isoelectric points as determined by chromatofocusing were 5.8 for the mitochondrial isozyme and 5.0 for the cytosolic isozyme. The purified isozymes were readily separable on ion exchange columns, with the cytosolic isozyme showing the greater affinity. A minor amount of cross-reactivity was apparent when each isozyme was immunotitrated with polyclonal antibodies raised in goat against the opposite isozyme. Peptide maps obtained by high pressure liquid chromatography of both tryptic digests and cyanogen bromide digests of the isozymes showed that many of the peaks were not coincident, suggesting that differences in the sequences are found throughout the primary structures of the isozymes. PMID- 3334873 TI - Thermodynamic study of the influence of NADPH on the binding of methotrexate and its metabolites to a mammalian dihydrofolate reductase. AB - Interaction of methotrexate and some of its metabolites with a mammalian dihydrofolate reductase was studied using two complementary methods, potentiometry and microcalorimetry. The major plasma metabolite of this anticancer agent, 7-hydroxymethotrexate, was found to have a different binding behavior from that of polyglutamyl derivatives and of methotrexate itself. Indeed, 7-hydroxymethotrexate binds without a pK shift to dihydrofolate reductase, whereas polyglutamyl derivatives bind to the enzyme with a proton uptake, as the parent drug does. NADPH increases the association constant of the 7-hydroxy metabolite by a factor of 10-20, while for methotrexate and for polyglutamates this increase is about 100-fold. It was demonstrated that the enhancement of the binding by NADPH had an enthalpic origin. Finally, the binding behavior of dihydrofolate reductase seemed to be independent of its enzymatic activity. PMID- 3334874 TI - Radioimmunofixation of human ferritin following serum isoelectric focusing. AB - Radioimmunofixation of human ferritin following isoelectric focusing of serum was developed to study the microheterogeneity of this protein in native serum without previous purification or concentration. This method requires only 2-10 microliter of serum and can be used with levels of ferritin as low as 10 micrograms/l. In this way, the extensive microheterogeneity of this protein was revealed, since in some cases it produced as many as 35 bands with isoelectric points in a pH range of 4.95-5.9. Very different isoelectric focusing patterns (spectrotypes) of ferritin were observed during the investigation of pathological sera. The high sensitivity of this technique makes it useful for the investigation of serum ferritin in diseases involving modifications of the metabolism of this protein. PMID- 3334875 TI - Analysis of F9 embryonal carcinoma cell lactosaminoglycans in relation to their differential expression during induction of differentiation. AB - Teratocarcinoma stem cells can be used to study the events related to early differentiation, and many cell surface changes have been described which correlate with the different stages of early embryogenesis. In this work we analyze the [3H]galactose-labeled glycopeptides derived from the mouse embryonal carcinoma cell line F9. We show that the high-molecular-weight glycopeptides typical of embryonal carcinoma cells are composed of two distinct molecular weight classes, namely H1 and H3, and that retinoic acid-induced differentiation determines a relative increase of the larger peak (H1) which is mainly due to a decrease in the expression of H3 species. We also show that, beside this decrease, there is a greater increase in the expression of lower-molecular-weight species. Furthermore, we present evidence that H1 and H3 species are polylactosaminoglycans N-linked to the peptidic backbone, and that induction of differentiation determines slight modifications in the structure of such species. PMID- 3334876 TI - Examination of differences between benzo[a]pyrene and steroid hydroxylases in guinea pig adrenal microsomes. AB - The effects of antibodies to cytochromes P-45017 alpha,lyase and P-450C21 on benzo[a]pyrene hydroxylase activity were measured in microsomes from guinea pig adrenals. Anti-cytochrome P-45017 alpha,lyase IgG inhibited about 30% of the benzo[a]pyrene hydroxylase activity of the microsomes in the presence of excess amounts of the IgG, but anti-cytochrome P-450C21 IgG did not affect the activity. In a reconstituted system, consisting of cytochrome P-450, NADPH-cytochrome-P-450 reductase and dilauroylphosphatidylcholine, cytochrome P-45017 alpha,lyase catalyzed, in addition to steroid hydroxylation, benzo[a]pyrene hydroxylation, but cytochrome P-450C21 did not hydroxylate benzo[a]pyrene. Since anti-cytochrome P-45017 alpha,lyase IgG inhibited benzo[a]pyrene hydroxylase activity completely in the reconstituted system with cytochrome P-45017 alpha,lyase, the presence of non-inhibited benzo[a]pyrene hydroxylase in the microsomes suggests that the residual activity in the microsomes may be due to some enzyme other than cytochrome P-45017 alpha,lyase. Benzo[a]pyrene hydroxylase activity was detected in detergent-solubilized microsomes from which cytochrome P-45017 alpha,lyase was removed by using an immobilized anti-cytochrome P-45017 alpha,lyase IgG-Sepharose column. This shows the existence in microsomes of a benzo[a]pyrene hydroxylase other than cytochrome P-45017 alpha,lyase. Benzo[a]pyrene hydroxylase in the solubilized microsomes required O2, NADPH and NADPH-cytochrome-P-450 reductase for its activity and was inhibited by CO. This suggests that benzo[a]pyrene hydroxylase is a cytochrome P-450-dependent monooxygenase. This novel enzyme was also active in xenobiotic metabolism, such as 2-nitropropane denitrification and aminopyrine demethylation. PMID- 3334877 TI - Biochemical analysis of decreased ornithine transport activity in the liver mitochondria from patients with hyperornithinemia, hyperammonemia and homocitrullinuria. AB - Hyperornithinemia, hyperammonemia and homocitrullinuria (HHH disorder) is an inherited metabolic disorder which shows peculiar amino acid changes in the serum and urine. The primary defect is considered to be the transport of ornithine across the mitochondrial membrane, but there is no direct evidence for this so far. We have analyzed ornithine transport activities in the liver mitochondria from three patients with HHH disorder. In coupled liver mitochondria we demonstrated low activities of citrulline synthesis and low rates of ornithine uptake. However, there were no abnormalities in carbamoyl-phosphate synthetase activity, ornithine carbamoyltransferase activity, N-acetylglutamate levels or O2 uptake with succinate. We also performed a kinetic study of citrulline synthesis as a function of ornithine concentration. We found increased Km values for ornithine and varied Vmax values of citrulline synthesis, which suggested the presence of a mutant transport protein. From these results we conclude that the defect of hyperornithinemia, hyperammonemia and homocitrullinuria lies in the transport of ornithine across the mitochondrial membrane. PMID- 3334878 TI - Inhibitory effect of mannose on erythrocyte defense against oxidants. AB - The erythrocyte can phosphorylate a variety of hexoses. Since it can consume mannose and glucose equivalently in the hereditary deficiencies of hexokinase and phosphoglucose isomerase and since erythrocyte defense against oxidants is impaired in a variety of hereditary hemolytic anemias, we tested the hypothesis that mannose may be a significant alternative to glucose as a fuel for this defense system. Unexpectedly, mannose inhibited defense against oxidants as manifested by increased Heinz body formation when both normal and high reticulocyte erythrocytes were incubated with acetylphenylhydrazine (APH). Using APH as the oxidant, mannose-incubated erythrocytes had decreased reduced glutathione stability and impaired hexose oxidation by the pentose shunt compared to glucose-incubated erythrocytes. After incubation with mannose and APH, normal erythrocytes showed a decrease in ATP content. Approximately 25% of the consumed mannose accumulated in the erythrocytes as mannose 6-phosphate. Erythrocytes incubated with mannose and APH displayed a significant loss of redox potential as manifested by decreased NADH/(NADH + NAD+) and NADPH/(NADPH + NADP+) ratios. Since phosphomannose isomerase is the rate-limiting step for mannose metabolism, our results suggest that mannose impairs erythrocyte defense against oxidants by causing ATP depletion and by impairing the regeneration of reduced pyridine nucleotides by the Embden-Meyerhof and pentose phosphate pathways. PMID- 3334879 TI - GABA concentrations in forebrain areas of suicide victims. AB - Concentrations of GABA and seven other amino acids, including the neurotransmitters or neuromodulators taurine, glycine, aspartate, and glutamate, were determined in postmortem brain samples from suicide victims and normal controls. The five brain areas (caudate nucleus, nucleus accumbens, frontal cortex, amygdala, and hypothalamus) contained very similar concentrations of the amino acids in both groups. The only significant difference between the groups was a low glutamine concentration in the hypothalamus of suicide victims. Even when the data were adjusted for differences in tryptophan concentration, a putative biochemical index for agonal and postmortem changes of brain tissue, no new differences emerged in the concentrations of neuroactive amino acids between suicide victims and control subjects. PMID- 3334880 TI - Reduced beta-casein levels in milk samples from patients with postpartum psychosis. AB - Defatted breast milk from women with postpartum psychosis and from healthy lactating women was analyzed by high-resolution gel permeation chromatography as well as by sodium dodecyl sulfate (SDS) and urea polyacrylamide gel electrophoresis. The gel permeation procedure allowed quantitative analysis of milk proteins (including beta-casein) with minute amounts of defatted milk (10-15 microliter). By electrophoresis, further characterization of the protein pattern, including the beta-casein fraction, was obtained. Milk samples from five control and seven psychotic subjects were analyzed. The concentration of the beta-casein containing peak was significantly lower in milk samples from the psychotic group by both chromatography and electrophoresis. These lower levels of beta-casein may result from a higher rate of enzymatic degradation generating i.a. peptides with opioid activity, as shown earlier in plasma and CSF of women with postpartum psychosis. PMID- 3334881 TI - Olfactory deficits in schizophrenia. AB - Olfactory discrimination was measured in patients with schizophrenia who were on neuroleptic medication and was compared with other psychiatric patients receiving neuroleptics and normal controls. The performance of the patients with schizophrenia was significantly lower than the psychiatric and normal controls. The latter two groups performed at equivalent levels. The findings are discussed with respect to olfactory deficits found in patients with cerebral lesions and with abnormalities of specific neurotransmitter systems. PMID- 3334882 TI - Memory impairment in schizophrenic patients with tardive dyskinesia. AB - Memory functioning was contrasted in 40 schizophrenic patients with and without tardive dyskinesia (TD). Visual and verbal memory tests were used to investigate specific types of impairments. The presence of TD was ascertained using the Abnormal Involuntary Movement Scale (AIMS). TD patients scored significantly lower than non-TD patients on two measures of visual learning, though no differences were found for verbal learning or immediate recall. These results are consistent with previous reports that schizophrenic patients with TD demonstrate impaired cognitive functioning. They also raise the possibility that the neurochemical and structural changes underlying TD may produce specific deficits in memory for visual materials. In addition, a significant relationship was found between total score on the Brief Psychiatric Rating Scale (BPRS) and performance on all of the test measures included in the cognitive test battery. This demonstrates the importance of attending to the overall level of schizophrenic symptomatology when evaluating results from experimental learning tasks. PMID- 3334883 TI - Peripheral serotoninergic receptor sensitivity in senile dementia of the Alzheimer type. AB - Platelet aggregation induced by 5-hydroxytryptamine (5-HT) was used as a measure of the functional responsiveness of peripheral 5-HT receptors in controls and drug-free patients suffering from senile dementia of Alzheimer type (SDAT). No significantly different aggregatory response (5-HT/ADP ratio) was noted between the two groups of subjects. If the receptor mediating this response is a 5-HT2 receptor, there is no evidence to suggest that the functional activity of this system is abnormal in SDAT. PMID- 3334884 TI - Ketamine as a pharmacological model for tongue dyskinesia. AB - The purpose of this article is to document that ketamine hydrochloride, administered at an anesthetic dosage of about 100 mg/kg, produces tongue contractile activity in the rat. The methods for monitoring and quantitating ketamine-induced tongue contractions (KITCs) are described. We also found that neuroleptic agents consistently and readily abolish KITCs. On the basis of these observations and other pharmacological properties of ketamine, we propose that KITCs may be a useful model for studying neuroleptic-induced oral dyskinesia, e.g., tardive dyskinesia. Additional findings in support of this model are presented. PMID- 3334885 TI - Chronic treatment with amitriptyline produces supersensitivity to nicotine. AB - The authors used a thermoregulation paradigm to evaluate effects of amitriptyline (AMI) on the sensitivity of a nicotinic mechanism involved in the regulation of core temperature in rats. Treatment with this tricyclic was associated with a significant increase in the hypothermic response to nicotine. Supersensitivity persisted for a minimum of 7.5 days following the last dose of AMI, and a significant proportion of animals displayed increased sensitivity after 14.5 days of abstinence. Implications for the mechanism of action of AMI are highlighted. PMID- 3334886 TI - Electroconvulsive treatment of a patient with known intracranial tumor. PMID- 3334888 TI - Creation, evolution, and biological psychiatry. PMID- 3334889 TI - Glycine therapy of schizophrenia. PMID- 3334887 TI - Combined lithium-tricyclic treatment of obsessive-compulsive disorder. PMID- 3334890 TI - Pisa syndrome in Alzheimer's disease. PMID- 3334891 TI - Amitriptyline and cholinergic supersensitivity. PMID- 3334892 TI - Identification of high-affinity (Kd 0.35 mumol/L) and low-affinity (Kd 7.9 mumol/L) platelet binding sites for ADP and competition by ADP analogues. AB - Steady-state binding of ADP to blood platelets and isolated membranes has not previously been obtained because of complications arising from metabolism of the ligand and dilution due to its secretion from storage granules. In the present studies, competition binding isotherms (n = 9) using paraformaldehyde-fixed platelets showed that [2-3 H]ADP bound to two sites with a small amount (approximately 5% of total) of nonspecific binding: 410,000 +/- 40,000 sites of low affinity (Kd 7.9 +/- 2.0 mumol/L) and 160,000 +/- 20,000 sites of high affinity (Kd 0.35 +/- 0.04 mumol/L) corresponding to the ADP concentration required for activation in fresh platelets (0.1-0.5 mumol/L). All agonists and antagonists examined were able to compete with ADP at the high-affinity site. The strong platelet agonists 2-methylthio ADP and 2-(3-aminopropylthio)ADP competed with ADP at the high-affinity site with dissociation constant values of 7 mumol/L and 200 mumol/L, respectively. The partial agonist 2',3'-dialdehyde ADP and the weak agonist GDP also competed at the high-affinity site with Kd values of 5 mumol/L and 49 mumol/L, respectively. The sequence of binding affinities of other adenine nucleotides at the high-affinity site corresponded to their relative activities as known antagonists of platelet activation by ADP; namely, ADP(Kd 0.35 mumol/L) approximately equal to ATP (Kd 0.45 mumol/L) much greater than AMP (Kd 360 mumol/L). Adenosine and 2-chloroadenosine did not compete with ADP. ADP binding to the high-affinity site was inhibited by p-mercuribenzene sulfonate (Ki 250 mumol/L) but only very weakly by 5'-p-fluorosulfonylbenzoyladenosine (Ki 1 mmol/L). All the above nucleotides also competed with ADP at the low-affinity sites but, because of the high concentrations of competing nucleotide required, dissociation constants at this site were obtained only for ATP (21 mumol/L), 2 MeS ADP (200 mumol/L) and 2',3'-dialdehyde ADP (270 mumol/L). 8-Bromo ADP competed strongly with ADP at the high-affinity site (Kd 0.40 mumol/L) but weakly if at all at the low-affinity site. 8-Bromo ADP inhibited platelet activation induced by ADP (EC50 approximately 100 mumol/L) but not by collagen, thrombin, or ionophore A23187.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3334894 TI - Effects of the cell adhesion peptide, Arg-Gly-Asp-Ser, on responses of washed platelets from humans, rabbits, and rats. AB - Fibrinogen is a cofactor in the aggregation of human platelets, and is required for ADP-induced aggregation of washed platelets; however, exogenous fibrinogen is not required for ADP-induced aggregation of washed platelets from rabbits or rats. Because with human platelets the cell adhesion peptide, Arg-Gly-Asp-Ser (RGDS), inhibits aggregation and the binding of 125I-fibrinogen to ADP-stimulated platelets, its effects on rabbit and rat platelets were studied to investigate the differences in the fibrinogen requirements of platelets from the three species. RGDS (50 mumol/L) caused greater than 80% inhibition of thrombin-induced or (ADP + fibrinogen)-induced aggregation of human platelets, but only 3% to 9% inhibition of the aggregation of rabbit or rat platelets, regardless of whether fibrinogen was added. RGDS inhibited the binding of 125I-fibrinogen to ADP stimulated human platelets by 80% to 90%, but by only 15% to 27% in the case of rabbit or rat platelets. The differences were due to the species of platelets, since human and rabbit fibrinogens gave similar results. In addition, RGDS failed to displace fibrinogen from the surface of rabbit platelets that had been stimulated with ADP. Thus, there are species differences in the ability of the cell adhesion peptide, RGDS, to block the platelet fibrinogen receptor, even within the mammalian species. PMID- 3334893 TI - Effective salvage therapy for lymphoma with cisplatin in combination with high dose Ara-C and dexamethasone (DHAP). AB - Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics. PMID- 3334896 TI - Cultured human umbilical vein endothelial cells contain a membrane glycoprotein immunologically related to platelet glycoprotein Ib. AB - Using a platelet glycoprotein Ib (GpIb)-specific monoclonal antibody, AP-1, we have studied cultured human umbilical vein endothelial cells (HUVEC) for the presence of GpIb. Radiolabeled AP-1 bound specifically and saturably to HUVEC in suspension and detected a single class of binding sites (100,000/cell). When Triton X-100 extracts of HUVEC were chromatographed on wheat germ agglutinin (WGA)-Sepharose, radioiodinated, precipitated with AP-1, and subjected to reduced sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE), major radioactive bands of 228,000, 145,000, and 130,000 were seen. The latter two bands correspond to the 156,000 and 140,000 bands, representing GpIb alpha and glycocalicin, respectively, which are seen when platelets are subjected to the same procedure. The 228,000 band corresponds to a band previously noted in immunoprecipitates of platelet GpIb but not fully explained. When HUVEC were grown in the presence of 35S-methionine, extracted with Triton X-100, chromatographed on WGA-Sepharose, immunoprecipitated with AP-1, and subjected to reduced SDS-PAGE, radioactive bands of 210,000, 156,000, and 90,000 were seen. We conclude that cultured HUVEC synthesize and express on their surface a glycoprotein immunologically related to platelet GpIb. PMID- 3334895 TI - Phenotypic and molecular heterogeneity in Philadelphia chromosome-positive acute leukemia. AB - Philadelphia chromosome-positive (Ph1) acute leukemia is a heterogeneous subset of acute leukemia with a poor prognosis. We studied five patients to determine the potential for phenotypic and molecular heterogeneity. Cellular characterization studies included light myeloperoxidase (L-MPO), terminal deoxynucleotidyl transferase (TdT), ultrastructural MPO (U-MPO), and immunophenotyping by flow cytometry using T11, T3, T4, T8, Leu 1, B1, Leu 12, HLA DR (la), CALLA (J5), OKM1, My4, My7, My8, My9, and My10. DNA was analyzed for rearrangements of the breakpoint cluster region (bcr), immunoglobulin heavy chain, joining region (JH), immunoglobulin kappa light chain constant region (C kappa), and T cell receptor (TcR beta). RNA dot blots were hybridized by using molecular probes for MPO and TdT. We found that four of five cases were acute mixed-lineage leukemia (AMLL). One patient had acute unclassifiable leukemia. Of the four patients classified as having AMLL, three showed myeloid and lymphoid features, with one patient showing myeloid, T cell, and B cell features. The last case showed T cell and B cell features only. In one patient MPO/RNA was positive in spite of insufficient L-MPO or U-MPO to diagnose acute myelogenous leukemia (AML), thereby suggesting significant MPO gene expression before the production of sufficient MPO protein to meet the French-American-British criteria for AML. Three of the five patients showed rearrangement of bcr (cases 1, 2, and 5). Studies of these five patients support the concepts of molecular and phenotypic heterogeneity in Ph1 acute leukemia, demonstrate a high incidence of AMLL in this subset of acute leukemia, and support the use of lineage-associated molecular probes to define lineage at an earlier stage than previously possible. PMID- 3334898 TI - Estimation of hematopoietic clone numbers. PMID- 3334897 TI - Gene deletion in a patient with chronic granulomatous disease and McLeod syndrome: fine mapping of the Xk gene locus. AB - In a patient suffering from X-linked chronic granulomatous disease (X-CGD)--a disorder of phagocytesuperoxide generation--and McLeod syndrome, characterized by the absence of the red cell Kell antigen, we identified a deletion of the entire X-CGD gene by means of DNA hybridization with a cDNA probe. Our findings suggest that the X-CGD and McLeod loci are physically close in the p21 region of the X chromosome proximal to the Duchenne muscular dystrophy locus. PMID- 3334899 TI - Effect of RBCs on the activation of human complement by heparin-protamine complexes. AB - Complement activation on red cells by heparin-protamine complexes was studied by using whole human serum. C3 bound to red cells was measured by radiolabeled monoclonal antibody to C3, and fluid-phase C5a was determined by radioimmunoassay. Heparin and protamine in clinically relevant concentrations caused the binding of C3 to red cell membranes, and the measurement of C3 binding provided a sensitive indicator of complement activation produced by these complexes. Complement activation by these reagents occurred at concentration ratios of protamine and heparin at which protamine neutralized the anticoagulant effect of heparin. Heparin-protamine complexes appeared to bind to red cells and produce complement activation by the classic pathway. C5a generation with heparin protamine complexes in serum was greatly enhanced in the presence of red cells and increased with increasing red cell concentration. This enhancement of complement activation in the presence of red cells was also seen as measured by depletion of available C3 hemolytic complement units in the fluid phase. Thus red cells seem to play an important role in activation of complement by heparin protamine complexes. PMID- 3334900 TI - The effect of deoxygenation rate on the formation of irreversibly sickled cells. AB - The effects of the deoxygenation rate on the formation of irreversibly sickled cells (ISCs) were investigated by using metabolically replete sickle cells (SS cells). We found that the formation of ISCs required Ca2+ and that the amount formed depended on the rate of deoxygenation. When less dense SS discocytes were deoxygenated slowly by flushing with 95% N2 and 5% CO2 at a rate of 3 mL/min, the percentage of ISCs increased from 5% to 26.5% after 24 hours. In contrast, upon rapid deoxygenation (10, 35 mL/min) ISC formation was reduced significantly. The difference may be related to fact that more sickle-shaped cells were formed upon slow deoxygenation than upon the rapid deoxygenation that resulted in the formation of star-shaped and granulated cells. So-called ISCs were formed more easily from sickle-shaped cells. To express the shape of sickled cells numerically, we calculated the mean maximum cell length (MCL) after cells were incubated under various deoxygenation conditions. The MCL of slowly deoxygenated SS cells after 24 hours of incubation was about twice (20.0 +/- 7.0 micron) that of quickly deoxygenated (35 mL/min) SS cells (12.5 +/- 5.0 microns) (initial MCL, 8.0 +/- 1.0 micron). The decrease in potassium content was greater with slow deoxygenation than with rapid deoxygenation. Because the increase in sodium influx was less than that of potassium efflux under slow deoxygenation, SS cells became more dense than those rapidly deoxygenated. In the absence of Ca2+, morphological changes were the same as in the presence of Ca2+; however, under this condition there was no change in density, and no ISCs were formed regardless of the rate of deoxygenation. These results demonstrate that the number of ISCs formed correlates with the MCL. The length of fibers of sickle hemoglobin may be a determinant of the length of sickled cells. This suggests that membrane stretching plays an important role in cell density and irreversible membrane deformation. PMID- 3334901 TI - High hyaluronic acid and low dermatan sulfate contents in human pulmonary arteries compared to in the aorta. AB - We examined the glycosaminoglycan (GAG) components in human pulmonary arteries compared to those in the aorta. Definite changes in GAG contents and components were found between the pulmonary arteries and the aorta. The GAG content of the aorta was constantly higher than that of the pulmonary artery. As to the components of the arterial GAGs, however, hyaluronic acid comprised significantly higher proportions of total GAGs in the pulmonary arteries than in the aorta, whereas dermatan sulfate showed lower proportions in the pulmonary arteries than in the aorta. These significant differences are possibly due to either the effect of the continuously different blood pressure on the wall of these two types of arterial vessels or to constitutional changes of their fundamental structures associated with atherosclerosis. PMID- 3334902 TI - Evidence that rabbit 125I-antithrombin III binds to proteoheparan sulphate at the subendothelium of the rabbit aorta in vitro. AB - The endothelium of the rabbit thoracic aorta was removed from the vessel wall by one of two procedures, and the freshly exposed subendothelial surface was used for 125I-antithrombin III binding studies. Pretreatment of the subendothelium with either heparitinase or thrombin diminished the uptake of 125I-antithrombin III by up to 80%, whereas pretreatment with plasmin, hyaluronidase or FPR thrombin had little effect. Morphometric analysis of the subendothelium from enzyme-treated and -untreated tissues showed that, whereas plasmin, thrombin and heparitinase each caused a dramatic reduction of the large proteoglycan granules of the extracellular matrix, only exposure to heparitinase and thrombin caused a reduction in the small proteoglycans which populate the basement membrane of smooth muscle cells. Of the subendothelium-bound 125I-antithrombin III, more than 80% was efficiently removed by excess thrombin or by excess heparin. Evidence was obtained for the formation of high molecular weight thrombin-antithrombin III complexes. We conclude that antithrombin III binds largely to proteoheparan sulphate located in the basement membrane of the intimal smooth muscle cells for the purpose of inactivating certain proteases which arise during haemostatic change. PMID- 3334903 TI - Sensorimotor mapping and oropharyngeal reflexes in goldfish, Carassius auratus. AB - The vagal lobe of goldfish and some carps is a laminated, specialized lobe of the midmedulla containing both primary sensory terminals and primary motor neurons. Both the sensory and motor components are represented in the lobe in a matching, orotopic fashion, i.e. the oral cavity is mapped across the surface of the lobe. Anatomical tracing studies reveal that the circuitry exists for a point-to-point reflex system in which the superficial sensory layers are mapped directly onto the underlying motor layer. The utility of this relatively direct sensorimotor coupling appears to be in terms of sorting food within the mouth according to its gustatory properties. The direct coupling between the mapped sensory layer and the similarly mapped motor layer may be a useful model in which to study the evolutionary development of less tightly coupled sensorimotor systems. PMID- 3334904 TI - Between the retinotectal projection and directed movement: topography of a sensorimotor interface. AB - This article reviews some recent findings on the character of the neuronal organization lying between the optic tectum and motor pattern-generating circuitry in the case of orienting behaviors. It focuses on frogs but notes parallels to existing work on saccade control in mammals and suggests some additional ones for further exploration. In general, the map-like function of orienting does not appear to be subserved by a comparable map-like organization. It is argued that the current conceptual vocabulary for describing interface organization (sensory map, motor map, pattern-generating circuitry) is inadequate and that some additional concepts (activity-gated divergence, intermediate spatial representation) are necessary. Finally, some questions are raised about the appropriateness of the term 'motor map'. PMID- 3334905 TI - Neural cartography: sensory and motor maps in the superior colliculus. AB - The sudden onset of a novel or behaviorally significant stimulus usually triggers responses that orient the eyes, external ears, head and/or body toward the source of the stimulus. As a consequence, the reception of additional signals originating from the source and the sensory guidance of appropriate limb and body movements are facilitated. Converging lines of evidence, derived from anatomical, electrophysiological and lesion experiments, indicate that the superior colliculus is an important part of the neural substrate responsible for the generation of orienting responses. This paper briefly reviews the functional organization of the mammalian superior colliculus and discusses possible linkages between the sensory and motor maps observed in this structure. The hypothesis is advanced that the sensory maps are organized in motor (not sensory) coordinates and that the maps of sensory space are dynamic, shifting with relative movements of the eyes, head and body. PMID- 3334906 TI - Electrosensory maps form a substrate for the distributed and parallel control of behavioral responses in weakly electric fish. AB - Electroreceptors, distributed over the body surface of weakly electric fish, code the local amplitude and phase, or timing of zerocrossing, of the animal's electric signals. These signals are generated by rhythmic discharges of the electric organ and form a dipole-like field around the animal. This field is perturbed by interference with electric fields of other fish as well as by the appearance of objects electrically different from water. The spatial and temporal structure of such perturbations can be interpreted as the electric image of interfering fields and moving objects. This strategy of assessing the environment is called 'electrolocation', a form of 'seeing' with the body surface. Electric images are analyzed in somatotopically ordered strata of neurons within the central nervous system. Primary electrosensory afferents project to somatotopically ordered layers of higher-order neurons in the electrosensory lateral line lobe (ELL) of the hindbrain. Phase and amplitude information are processed in separate layers of the ELL. The phase of the signal in a given region of the body surface is coded by the timing of spikes of spherical cells marking the zerocrossings of the electric signal. This phase information is relayed to lamina 6 of the torus semicircularis of the midbrain. Rises and falls in local amplitude are coded by the activity of different pyramidal cell types, E and I-units, which project to various laminae of the torus above and below lamina 6. The somatotopic organization of the torus allows for computations of spatial patterns in electrosensory information. Within lamina 6, differences in the phase of signals from different parts of the body surface are computed. Differential-phase information is then relayed to deeper laminae of the torus and remains in topographic register with amplitude information. This organization allows for joint evaluation of spatially related patterns of amplitude and phase modulations on the animal's body surface within local neuronal circuits of the torus. A topographic projection of the torus relays amplitude and differential phase information to the optic tectum where a further joint evaluation of amplitude and phase serves to control behavioral responses. The control of a particular behavioral performance, the 'jamming avoidance response', is of a distributed nature in that the representations of individual sites on the body surface contribute cumulatively to shift the electric organ pacemaker frequency.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3334907 TI - The diagnosis of dementia. PMID- 3334908 TI - Continuing education through Telemedicine for Ontario. PMID- 3334910 TI - Public policies and the health of children. PMID- 3334911 TI - New sleep disorder. PMID- 3334909 TI - Fluoridation: why is it not more widely adopted? PMID- 3334913 TI - Blood glucose monitoring devices: the need for education, supervision and control. PMID- 3334912 TI - Methadone treatment in Canada: the clinical questions continue. PMID- 3334914 TI - Guidelines on the use of blood glucose meters and nonmeter blood glucose reagent strips in hospitals. Committee on Monitoring Devices, Canadian Association of Pathologists. AB - A cross-sectional survey of Canadian hospitals carried out in 1984 revealed a large diversity of practices in the use of blood glucose meters and nonmeter blood glucose reagent strips and of providers of this service. Most hospitals lacked guidelines and acceptable delegation of quality control. The results prompted the Committee on Monitoring Devices of the Canadian Association of Pathologists, composed of representatives of the medical profession, professional organizations, industry and an accrediting organization, to develop guidelines on the use of blood glucose monitoring devices in hospitals. PMID- 3334915 TI - National surveillance program on occupational exposure to the human immunodeficiency virus among health care workers in Canada. PMID- 3334916 TI - Glove use for infection-control procedures. PMID- 3334917 TI - Spinal injuries due to front-end bale loaders. AB - Of 22 patients admitted to Plains Health Centre, Regina, from January 1979 to April 1986 with spinal injuries due to farming accidents, 7 had injuries related to tractor-mounted front-end bale loaders. In contrast, none of the 12 patients admitted with farm-related spinal injuries from 1974 through 1978 had injuries related to bale loaders. All seven injuries occurred when a front-end loader was used to move a large, round hay bale. In each case when the loader arms were raised past the horizontal plane the bale rolled back onto the unprotected tractor operator. There were five thoracic injuries, one cervical injury and one lumbar injury. All seven bony injuries healed. Four of the patients had permanent neurologic sequelae; two of the four had paraplegia. All seven patients suffered disability that impaired work performance; all five farmers suffered some loss of income. None of these injuries would have occurred if available safety equipment had been in place. PMID- 3334918 TI - Elinor Caplan: She wants to build some bridges to Ontario doctors. Interview by Charlotte Gray. PMID- 3334919 TI - Animal rights: a volatile issue. PMID- 3334920 TI - "Why can't I sleep?". PMID- 3334921 TI - The diagnosis of dementia. PMID- 3334923 TI - Cocaine-induced central retinal artery occlusion. PMID- 3334922 TI - Endometrial carcinoma: feasibility of case-finding in a family physician's office. AB - To study the feasibility of endometrial sampling in a family physician's office we examined 42 asymptomatic women 50 years of age or older with the use of a Milan-Markley helix to obtain cytopathologic material. Nine procedures could not be completed because of stenosis of the introitus or cervix. The procedure took less than 3 minutes to complete for 30 women, and there was no technical difficulty for 27. Adequate amounts of tissue for diagnosis were obtained from 32 women. One or more risk factors for endometrial carcinoma were present in 34 women. Nine samples showed atypical hyperplasia. Although 37 women experienced discomfort and 19 experienced spotting, 35 were willing to have the procedure repeated annually or as indicated by their physician. PMID- 3334925 TI - Chickenpox in Canada, 1924-87. AB - Because of the lack of an effective vaccine and the difficulty in implementing any effective control measures, physicians and public health practitioners have paid little attention to understanding the epidemiologic features of chickenpox. No data on the incidence rate in Canada are available for 1959-85. However, Ontario data suggest an overall decrease in the annual rate during the 1960s and a stable rate since the mid-1970s. High incidence rates are expected among children 5 to 9 years of age because of their susceptibility and their greater exposure in school. Low incidence rates among older age groups are expected, because most of these people have already been exposed to the virus. The disease is more serious among infants than among other children. The risk of death from chickenpox is also highest among infants. More patient-specific information and improved collection of incidence data are required to measure any impact from future control procedures, including the use of vaccines currently being developed. PMID- 3334924 TI - Subacute lead poisoning from retained lead shot. PMID- 3334926 TI - A case of mumps meningitis: a complication of vaccination? PMID- 3334928 TI - Preparing for the worst: medical services at the Calgary Olympics. PMID- 3334927 TI - The drug bill: to the Americans it's only a start. PMID- 3334930 TI - Spectator events: medical preparation a must. PMID- 3334929 TI - Red Cross gets go-ahead for autologous blood service. PMID- 3334931 TI - Infertility giving birth to new problems for doctors and lawyers. PMID- 3334932 TI - Agricultural medicine: fighting health hazards down on the farm. PMID- 3334933 TI - Nonprescription availability of antiasthma drugs. PMID- 3334934 TI - Tobacco bill in jeopardy without MD support. PMID- 3334935 TI - Distant metastases in papillary thyroid cancer. A review of 91 patients. AB - Of 731 patients with papillary thyroid cancer, 91 had metastases outside regional lymph nodes. The most common site was intrathoracic, occurring in 73 of the 91 patients. Miliary, micronodular pulmonary metastases, with iodine 131 (I-131) uptake and "curable" by I-131 treatment were encountered in seven patients. It has not been established whether this was a transient stage in additional patients. In 38 patients rounded, macronodular pulmonary metastases were found. Another 21 patients had unilateral pulmonary infiltration and mediastinal enlargement. Pulmonary infiltrations may be hematogenic, or may possibly occur via regional, mediastinal lymph nodes. Mortality within 1 year of the diagnosis of distant metastases exceeded 50%. Occurrence of distant metastases showed a slight but highly significant association with male sex, advanced age, and advanced local tumor stage. Better prognostic determinants are, however, required if adequate of the individual patient with papillary thyroid cancer is to be achieved. PMID- 3334936 TI - Cytophotometric measurements of Hurthle cell tumors of the thyroid gland. Correlation with pathologic features and clinical behavior. AB - The DNA content and nuclear size and shape of 21 Hurthle cell neoplasms of the thyroid were analyzed with a CAS 100RS Image Analyzer (Cell Analysis Systems, Lombard, IL) in order to distinguish between benign and malignant lesions. Neoplasms were considered malignant if documented metastatic disease or pathologic evidence of vascular or capsular invasion was present. Of the ten neoplasms classified as malignant, eight were aneuploid and two were diploid. Nine of the 11 benign neoplasms were diploid, the remaining two neoplasms were aneuploid. Two of the four malignant neoplasms which recurred or metastasized were aneuploid, the other two were diploid. A statistically significant association was found between aneuploidy and tumor invasion (P = 0.007). However, measurement of the percentage of cycling tumor cells as well as nuclear size and shape were not useful in separating benign from malignant neoplasms. PMID- 3334937 TI - Flow cytometric DNA ploidy in colorectal adenomas and family history of colorectal cancer. AB - Flow cytometric DNA ploidy of colorectal adenomas resected from 34 patients and the corresponding patient family history in first-degree relatives were evaluated. The samples with at least two separate G0-G1 peaks were defined as DNA aneuploid. The correlation between DNA ploidy and family history was evaluated using two-by-two contingency tables. This correlation was highly statistically significant: seven of nine patients (78%) with positive family histories, and five of 25 (20%) with negative family history had adenomas with DNA aneuploid stemlines (P = 0.0068). The overall DNA aneuploidy incidence was 12 in 34 cases (35.2%). The combined information of DNA aneuploidy and positive family history of colorectal cancer in patients with colorectal adenomas may help to better understand the process of colon carcinogenesis and to identify patients who have a higher risk for developing a malignancy. PMID- 3334938 TI - Flow cytometric analysis of DNA and cell proliferation in ovarian tumors. AB - DNA content in tumor cells from 50 patients with ovarian tumors was analysed by flow cytometry (FCM). Solid tissue samples were processed to obtain monodispersed cells. Staining for DNA analysis was achieved with ethidium bromide and mithramycin. Peripheral blood lymphocytes were used as reference diploid cell population. All benign ovarian tumors exhibited only diploid cells. DNA aneuploid cell lines were found 66.6% of serous carcinomas and in 80% of malignant granulosa cell tumors. The S-phase fraction of DNA diploid cells in benign ovarian tumors (S = 2.4 +/- 1.2%) was smaller than those of malignant tumors (S = 8.2 +/- 5.2%). DNA aneuploid cell populations in serous carcinomas display a higher S-phase fraction (S = 19.2 +/- 9.3%) than DNA diploid cells (S = 11.7 +/- 3.2%). No major differences were obtained between primary ovarian tumors and their metastases, as far as degree of aneuploidy and S-phase fraction are concerned. A high degree of correlation was established between the grade of differentiation of ovarian tumors and the DNA ploidy abnormalities. PMID- 3334939 TI - Interinstitutional variability in DNA flow cytometric analysis of tumors. The National Cancer Institute's Flow Cytometry Network Experience. AB - Flow cytometric DNA analysis of human urinary bladder specimens may be clinically useful for prognosis in transitional cell (urothelial) carcinoma and for detecting recurrence after treatment. However, many important methodological differences exist among institutions which have described this technique, and it has not previously been shown that data from different institutions are comparable. The National Cancer Institute has created a Flow Cytometry Network to address the need for technology assessment of flow cytometry. This report describes the independent flow cytometric analysis and interpretation of "unknown" paraffin-embedded bladder tumor specimens by the five Network institutions. Although important differences in method existed among the institutions, substantial agreement was achieved in actual data generated and their interpretation. This suggests that a consensus regarding acceptable laboratory performance of this technique could be reached, which should facilitate its more widespread clinical implementation. PMID- 3334941 TI - Juvenile fibromatosis resembling aponeurotic fibroma and congenital multiple fibromatosis. One case with pleuropulmonary involvement. AB - This article deals with a young school boy born in 1971 with a tumor in the palm of his right hand. We have considered this a juvenile aponeurotic fibroma. This tumor has recurred several times, leading to unavoidable amputation of the right wrist and hand. Seven years after the initial diagnosis, the axillary area became involved, then the pleura and lung. Such an unusual process leads to reconsidering the diagnosis and to regard this case as an intermediate form between Keasbey's juvenile aponeurotic fibroma and generalized fibromatosis. PMID- 3334940 TI - Double alkylating agent therapy with ifosfamide and cyclophosphamide for advanced non-small cell lung cancer. From the Manchester Lung Tumour Group. AB - Forty-five patients with advanced non-small cell lung cancer (NSCLC), with progressive inoperable tumors were treated. Twenty-three patients were of "limited" stage. Six patients had received previous thoracic radiotherapy. Patients with central nervous system (CNS) metastases, Karnofsky scores of less than 30 or more than 70, and patients over 70 years of age were excluded from the study. Cyclophosphamide (2.5 g/m2) was infused intravenously over 3 hours with the same Mesna dose. At the midpoint of the infusion, 3.5 g/m2 infosfamide was delivered as a bolus. Additional Mesna was administered over the next 8 hours. A maximum of four courses were given at three weekly intervals. One-hundred-thirty eight courses were administered and 53% of patients completed all four treatments. The response rate was 38%, with three (7%) complete responses. Seven additional patients (15%) with stable disease symptomatically improved by two steps or more on the Karnofsky scale at the end of treatment. Median survival for all 45 patients was 7 months, range less than 1 to 25 months. Sixteen courses were complicated by Grade 3 thrombocytopaenia and/or leukopenia (Grade 4 on six occasions, Grade 3 on seven occasions) on the blood count taken immediately before chemotherapy. Intravenous antibiotics were required on 14% of the total number of courses; and three patients died of probable treatment related causes. Two episodes of severe ifosfamide encephalopathy occurred but recovery was complete, and four episodes of frank hematuria also occurred. The Karnofsky score was more than 70 in 33% of patients one month after the end of chemotherapy compared with 0% before treatment. Unlike many chemotherapeutic regimens for NSCLC, double alkylating agent treatment with ifosfamide and cyclophosphamide improved the performance status without major toxicity in a selected patient population. The overall survival, however, remains short and further alkylating agent combinations need to be considered in the future. PMID- 3334942 TI - Treatment of retinoblastoma. Results obtained from a prospective study of 51 patients. AB - During 4 years, 51 patients with retinoblastoma were studied (unilateral 32, and bilateral 19). Treatment consisted of enucleation of those eyes which showed massive involvement followed by radiotherapy when there was optic nerve and/or orbit involvement. Systemic chemotherapy was administered to all patients who underwent nonsurgical treatment and when the histologic examination showed choroidal optic nerve head and/or optic nerve involvement or residual tumor after enucleation. When there was compromise of the central nervous system intrathecal chemotherapy was administered. Nonsurgical treatment consisted of radiotherapy and/or light coagulation. Survival was 90.6% for unilateral cases and 84.2% for the bilateral. The median follow-up was 31 months and 29 months, respectively. Of 19 conservated eyeballs, 16 preserve useful vision (63%). PMID- 3334943 TI - Laryngeal carcinoma in black patients. AB - The majority of reports on laryngeal carcinoma are from institutions serving a mostly white population. This report is about laryngeal carcinoma in black patients at Harlem Hospital Center. In a retrospective analysis, 113 patients (male-female, 3.5:1) with carcinoma of the larynx were examined. Sixty-seven patients (59%) were between 50 and 60 years of age. There were two patients (2%) with carcinoma in situ, 15 (13%) in Stage I, 40 (35%) in Stage II, 39 (35%) in Stage III, and 15 (13%) in Stage IV. Of the 113 patients, 70 (62%) were treated surgically, Group I; 24 (21%) received radiotherapy only, Group 2; and 19 (17%) refused treatment or died before therapy initiation. For patients in Group 1, the 1-year survival rate was 68% (43 of 63), the 3-year survival rate was 38% (20 of 53), and the 5-year survival rate was 15% (7 of 47). For Group 2, the survival rate was 48% (11 of 23), 30% (7 of 23), and 14% (3 of 22), respectively. In this patient population, laryngeal carcinoma occurred at a younger age than other reported groups, had a higher incidence in females, and had a lower 1-, 3-, and 5 year survival rate. PMID- 3334944 TI - The relationship of dietary intake and serum levels of retinol and beta-carotene with breast cancer. Results of a case-control study. AB - The possible association between the risk of breast cancer, blood level, and dietary intake of preformed Vitamin A (retinol) and beta-carotene was investigated in a case-control study carried out from May 1982 to June 1985. The patients studied were 214 previously untreated individuals with T1-2, N0-1, M0 breast cancer admitted to the National Cancer Institute of Milan and 215 controls admitted for conditions other than neoplastic or metabolic disorders. Both cases and controls were selected from an age group ranging from 30 to 65 years old. Plasma levels of retinol and beta-carotene were tested from blood samples drawn during the first day after admission to the hospital. A questionnaire about diet was used to estimate the mean intake of 69 food items from which a daily dietary index of retinol and beta-carotene intake was computed. Information relating to the woman's history, socioeconomic status, and known risk factors for breast cancer was also collected. No association was found between beta-carotene (in the diet or blood) or dietary retinol and the risk of breast cancer. As for blood retinol, our data show a significant trend of increasing risk with higher levels; multivariate relative risk for subsequent serum levels based on the control quintiles, are 1, 1.5, 1.8, 1.7; (test for linear trend: chi-square = 8.26). Thus, these findings, together with the results of other studies, suggest that retinol and beta-carotene are unlikely to be related to the risk of breast cancer. PMID- 3334945 TI - Risk of breast cancer among Greek women in relation to nutrient intake. AB - A case-control study of the role of diet in the cause of breast cancer was conducted in Athens, Greece. The case series consisted of 120 consecutive patients with histologically confirmed breast cancer admitted to either of two teaching hospitals over a 12-month period. The controls were 120 patients admitted to a teaching hospital for trauma and orthopedic conditions during the same period. Dietary histories concerning the frequency of consumption of 120 foods and drinks were obtained by interview. Nutrient intakes for individuals were estimated by multiplying the nutrient content of a selected typical portion size for each specified food item by the frequency that the food was used per month and summing these estimates for all food items. Cases reported significantly less frequent consumption of vitamin A after controlling for total caloric intake, potential external confounding variables and other nutrients associated with breast cancer risk. The odds ratio estimated for consumption of vitamin A equal to the value of the 90th centile versus consumption equal to the value of the 10th centile was 0.46 with 90% confidence limits 0.26-0.82. There was no evidence that high intake of dietary fat increases the risk of breast cancer. PMID- 3334946 TI - Recurrence of Hodgkin's disease 29 years later. AB - This article documents a case of recurrence in Hodgkin's disease, lymphocyte depletion type, 29 years after remission. This is the longest remission reported in the literature. PMID- 3334947 TI - Hodgkin's disease in black Zimbabweans. A study of epidemiologic, histologic, and clinical features. AB - A 3-year prospective study of the histologic and clinical features of patients with Hodgkin's disease presenting to the medical units in Harare, Zimbabwe, was undertaken. The histologic pattern of disease was similar to that of other African countries with mixed cellularity and lymphocyte depleted patterns prevailing (58% and 21%, respectively). Unlike most African countries, however, disease occurred most commonly in teenagers and young adults. Nutritional status was poor in just under 50% of the patients. Clinically, the extent of disease at presentation was striking, with over 90% of patients having advanced stage disease in spite of the stated duration of symptoms being moderate. The histologic and clinical findings resembled those reported from other African countries, but in certain aspects the epidemiologic pattern was intermediate between those of affluent and underprivileged communities. PMID- 3334948 TI - Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. AB - Most patients with metastatic prostate cancer will have metastasis to bone. Such patients are best monitored by serial radionuclide bone scans. One hundred sixty six men with bone metastasis from prostate cancer who received androgen deprivation therapy had their pretreatment bone scans reviewed using a semiquantitative grading system based upon the extent of disease (EOD) observed on the scan. The EOD on the scan correlated with survival. The 2-year survival rates for EOD I to IV were 94%, 74%, 68%, and 40%, respectively. The survival of patients in categories EOD I and IV significantly differed from the other categories. Men with metastatic prostate cancer entered into trials designed to evaluate the impact of treatment on survival should be stratified based upon the EOD on the bone scan. This analysis also indicates that patients in the EOD IV category have a particularly poor prognosis and may be candidates for alternative treatments. PMID- 3334949 TI - Squamous cell carcinoma of the upper aerodigestive tract. A case comparison analysis. AB - Although the etiologic importance of tobacco in risk of upper aerodigestive malignancies is unquestioned, quantification of subsite-specific risks is less well delineated. Risk estimates from this case-control study are derived from self-administered comprehensive risk factor questionnaires distributed to newly registered patients at The University of Texas M.D. Anderson Hospital and Tumor Institute, Houston. Cases included 185 white patients with histologically confirmed squamous cell carcinoma of the upper aerodigestive tract. An equal number of age-frequency and sex-frequency matched patients was randomly selected from the same patient population excluding only patients with diagnoses of squamous cell carcinoma of any site. A statistically significant dose-response relationship for three categories of cigarette pack-years was evident for both males (odds ratios [OR] = 1.8, 4.0, and 7.5) and females (OR = 1.5, 9.0, and 12.0). Highest risks were documented for laryngeal cancer (OR = 15.1) and lingual cancer (OR = 14.5). There was interaction between alcohol use and smoking among men, but no independent effect of alcohol consumption among either gender. After 15 years of smoking abstinence, males no longer exhibited increased risk (OR = 1.0) whereas the risk for females after 15 years of cessation was 1.5. There were also significantly increased risks among men associated with snuff dipping, cigar, and pipe use (OR = 3.4, 2.8, and 1.8, respectively). The differences in the magnitude of the risk estimates and dose-response curves by subsite and by sex suggest a variable susceptibility to carcinogenic action. PMID- 3334951 TI - Reversible ocular toxicity related to tamoxifen therapy. AB - A 42-year-old woman with metastatic breast cancer developed bilateral optic disc swelling, retinal hemorrhages, and visual impairment three weeks after starting treatment with low doses of tamoxifen. Neurologic evaluation failed to provide an explanation for the ocular findings which resolved completely after cessation of tamoxifen therapy. This case suggests that tamoxifen has the potential for causing serious ophthalmologic toxicity which may be reversible if recognized early. PMID- 3334950 TI - Multidisciplinary treatment of primary Ewing's sarcoma of bone. A 6-year experience of a European Cooperative Trial. AB - The German Society of Pediatric Oncology in 1981 initiated the Cooperative Ewing's Sarcoma Study (CESS 81) using a four-drug combination of chemotherapy prior to definitive local control with surgery and/or radiation. From January 1, 1981 until February 28, 1985, 93 patients were registered at the trial office from 54 participating institutions in West Germany, Austria, Switzerland, and the Netherlands. On February 1, 1987, 54 of 93 patients were disease-free. Using the Kaplan-Meier life table analysis, the estimated disease-free survival (DFS) rate was 60% at 36 months and 55% at 69 months. The median period of observation was 29 months, ranging from 22 months to 69 months. Twenty-one of 93 patients (23%) had local failure, 18 of 93 patients (19%) developed systemic metastases. The local failure rate was particularly high in patients treated with radiation and was reduced when radiation planning was centralized within the study based upon the extent of disease at diagnosis. Cox regression analysis of prognostic factors showed that tumor volume was a significant factor influencing prognosis. The estimated 3-year DFS rate was 80% for patients with small tumors (volume less than 100 ml) compared to 31% for patients with large tumors (volume greater than or equal to 100 ml). In patients who had surgery for local control, the histologic response to chemotherapy was analyzed on the surgical specimen and had a strong influence on survival: 79% DFS at 3 years for patients with less than 10% viable tumor (good responders) compared to 31% DFS for patients with more than 10% viable tumor (poor responders). Tumor load and responsiveness to chemotherapy are the two major factors influencing prognosis in patients with primary Ewing's sarcoma of bone. PMID- 3334952 TI - Reducing the negative impact of radiation therapy on functional status. AB - The effect of an informational intervention that provided objective descriptions, in concrete terms, of the usual experiences during the various phases of radiation therapy was tested in a random clinical trial. The patients had Stage A, B, or C prostatic cancer. Forty-two control patients received the information routinely provided to all patients in the treatment setting. Forty-two experimental patients received, in addition, four informational messages during the course of radiation therapy. The first message described the experience of treatment planning; the second described the experience of receiving a radiation treatment; the third described side effects that usually occur, their onset, their characteristics, and activities to lessen their impact; and the fourth described the usual experiences during the months following radiation treatments. The experimental group of patients, compared with those in the control group, reported significantly less disruption in usual activities during and following radiation therapy. The amount of emotional disturbance was low and did not differ by study group. The results of this study, with respect to the interventions' effect on radiation therapy patients' quality of life, were consistent with prior research in other health care situations. PMID- 3334953 TI - Instability of xenotransplanted soft tissue sarcomas. Morphologic and flow cytometric results. AB - Human tumors transplanted into nude mice are widely considered to be identical to the tumor of origin. In addition, high histologic constancy of xenografts over many passages is generally accepted. We have checked these prerequisites for a therapy-orientated application of the nude mouse model using soft tissue sarcomas. Twenty-two primary soft tissue sarcomas and their xenografts were compared histologically and flow cytometrically over numerous passages. More than 30% of transplants showed a variation in cell differentiation, cell content, frequency of mitosis, tendency to necrotize, and connective tissue content compared to the original tumor. Furthermore, transplants from various regions in one tumor showed divergent results. Analyses of serial transplants showed histologic and flow cytometrical discrepancies in about 50% of cases, and new cell lines occurred in 26%. Our results show that the genetic instability found in human neoplasias also applies to xenotransplants and that the therapy-related usefulness of the nude mouse model is limited. PMID- 3334954 TI - Acute leukemia and myelodysplasia in polycythemia vera. A clinical study with long-term follow-up. AB - The analysis of 288 cases of polycythemia vera (PV) with a minimal follow-up of 10 years enabled us to study the characteristics of acute leukemia as observed in 33 patients (11.4%). In 50% of the patients (16 of 33), the malignant transformation is of the refractory anemia with excess of blasts (RAEB) type. Half of these further transform to acute nonlymphocytic leukemia (ANLL). Their life expectancy is not better than patients who abruptly develop ANLL. Leukemic transformation shows a frequency peak in the eighth year after initial evaluation in PV treated with chemotherapy and in the 11th year in patients treated with radiotherapy. In 30% of the patients myelofibrosis, or the spent phase of PV, is present before the transformation to acute leukemia (AL). This complication is, however, part of the natural history of PV and is observed in 20% of PV patients at 10 years when leukemic transformation is absent. Marrow fibrosis can therefore not be considered as a preleukemic phase. It was also noted that the occurrence of myeloid metaplasia/myelofibrosis is more frequent and begins earlier in patients treated by phlebotomy alone, and who do not transform to leukemia. The clinical characteristics of these AL, including high frequency of partial marrow invasion, difficulties in cytologic classification, a peak incidence similar to that in patients treated by chemotherapy or radiotherapy for a prior malignancy, multiple chromosome abnormalities, and poor response to therapy are all highly suggestive of secondary leukemias. PMID- 3334955 TI - The value of bone marrow biopsy in breast cancer at time of diagnosis. A prospective study. AB - Bone marrow biopsies (BMB) were performed in 173 consecutive unselected breast cancer patients at the time of diagnosis to define the value of this diagnostic tool in the initial staging of mammary carcinoma. In a group of 160 patients with a negative standard staging work-up, BMB was positive in two (1%). Both of them had negative x-ray but bone scan was positive in one and doubtful in the other. Bone marrow biopsy was positive in 31% of 13 additional patients with metastatic disease and in 44% of the nine among them with radiologically involved skeleton. These results exclude that BMB is able to discover micrometastatic foci of neoplastic disease. Its positivity appears strictly correlated with that of bone x-ray and scan. Based on the results of this prospective study, BMB is not required when both bone survey and scan are negative, but could be useful in clarifying diagnostic doubts of skeletal involvement. PMID- 3334956 TI - Analysis of dose fractionation in the palliation of metastases from malignant melanoma. AB - Sixty-five visceral metastases from malignant melanoma were treated with radiation therapy. A variety of total doses and dose fractions were used. Significant palliation was achieved in 40 of 65 (62%) symptomatic lesions. There was no correlation between total dose or dose fraction size and significant palliation. Brain and bone metastases were separately analyzed. Nineteen of 28 (68%) bone metastases were palliated. Appendicular bony metastases were more likely to be palliated than axial bony metastases (88% versus 60%). The palliation of bone metastases did not depend on total dose given or fraction size. Nine of 23 (39%) symptomatic brain metastases were palliated. There was no difference in the rate of palliation between solitary and multiple brain metastases. Palliation of brain lesions was not dependent on fraction size, although there was a trend to better palliation with higher total doses. These findings suggest that unlike treating cutaneous or nodal melanoma lesions for local control, there is no advantage in large fraction size when treating with palliative intent visceral melanoma lesions. PMID- 3334957 TI - Respiratory tract fistulae in recurrent aerodigestive cancers after chemotherapy. AB - Bronchoesophageal fistulae, a form of respiratory tract fistula, occurred in four patients with squamous cell carcinoma arising in the esophagus or left bronchus after cytoreductive chemotherapy. All four had locoregional cancer, recurrent after high-dose external radiation therapy. Esophageal cancer was treated with sequential intravenous cisplatin 100 mg/m2 (day 1) and 5-fluorouracil (5-FU) 40 mg/m2/hour X 120 (days 2-7). Lung cancer was treated with sequential intravenous cisplatin 100 mg/m2 (day 1), 5-FU 40 mg/m2/hour X 72 (days 2-5), and etoposide 80 mg/m2/day X 3 (days 2, 3, and 4). All patients had symptomatic relief and tumor regression after oncolytic chemotherapy, which was well tolerated with no hematologic toxicity. After the second or third cycle of chemotherapy, bronchoesophageal fistula occurred in all four patients with manifestations of pneumonia, which proved fatal in two patients. The other two patients were effectively palliated for 14 and 36+ weeks after celestin tube placement. Bronchoesophageal fistula should be managed by antibiotics and respiratory support followed by elective placement of celestin tube in most patients and by esophageal exclusion or esophageal bypass in a few select patients. In aerodigestive cancers, respiratory tract fistula may be a rare and potentially fatal complication of chemotherapy induced tumor lysis. PMID- 3334958 TI - Mammary carcinoma developing after radiotherapy and chemotherapy for Hodgkin's disease. AB - Two patients developed breast cancer after treatment of Hodgkin's disease. Both had received mediastinal irradiation 13 to 15 years, respectively, before the diagnosis of breast carcinoma. One patient had synchronous bilateral breast cancer when the diagnosis was made. Discussed is the risk of mammary carcinoma as a second malignant neoplasm in patients treated for Hodgkin's disease. PMID- 3334959 TI - A comparison of preoperative radiotherapy regimens for bladder carcinoma. The University of Pennsylvania experience. AB - Between 1976 and 1985, 155 patients from the Hospital of the University of Pennsylvania, the Philadelphia Veterans Administration Hospital, and the Fox Chase Cancer Center were divided into groups, each of which was treated with one of three preoperative radiotherapy regimens to be followed by cystectomy. Patients initially were treated with 4000 cGy during 4 weeks followed by cystectomy (16 patients). Beginning in 1978, patients received 2000 cGy in 1 week prior to surgery (70 patients). Since 1982, 40 patients were treated with 500 cGy on the day prior to surgery with postoperative radiation therapy reserved for patients with either involved margins of resection, advanced stage or high grade. A fourth group of 20 patients was either not offered or refused preoperative radiation. Nine patients received only postoperative radiation therapy. The 5 year actuarial disease-free survival for pathologic Stages B2, C, and D lesions (T3-4, N0-2), was 63% for those who had received high-dose radiation versus 21% for those that had low-dose or no radiation. Patients with advanced pathologic stage disease who had received greater than 2000 cGy had a reduced rate of local failure (11% versus 27% for those who had received less treatment). Patients with abnormal upper tracts as shown on the intravenous pyelograms (IVP) had a reduced 5-year determinate survival of 23% versus 65% for patients with normal upper tracts. This condition did not independently affect survival, but rather reflected advanced stage. Patients with abnormal creatinine levels had a decreased survival that was independent of stage. Computed tomography was found to have low sensitivity for determining extravesical extension (39%) and metastatic lymphadenopathy (12%). Patients with clinical Stage B2 and C disease (T3) that were downstaged had a 63% 5-year survival versus 18% of those that were not downstaged. The incidence of both ureteroenteral strictures and stomal complications was found to be higher in the 2000 cGy group than in those patients treated with the other regimens. The overall incidence of complications in that group was also significantly greater. We conclude that there is a continuing role for adjuvant radiotherapy in invasive bladder carcinoma to improve both pelvic control and survival. The 500 cGy radiotherapy "sandwich" regimen was equal in terms of pelvic control and survival to the other regimens and showed less overall morbidity. The 2000 cGy regimen was associated with the greatest incidence of morbidity and did not substantially improve pelvic control. PMID- 3334960 TI - Mammography and palpable cancer of the breast. AB - The statistical analysis documented in this article was performed to determine the accuracy of mammography in diagnosing a palpable cancer of the breast. All of the women studied underwent mammography after the discovery of the cancer, which was proven by biopsy; the cancer did not involve the skin. All mammograms that demonstrated any abnormality in the area of the cancer were deemed to be positive. This study demonstrates that 22% of the women who have a palpable cancer of the breast will have a false-negative mammogram; 44% will be women of 50 and younger, and 13% will be women more than 50 years of age. Mammography is detrimental if used to avoid biopsy when there is a persistent mass, especially in younger women. It is concluded that biopsy should be performed on every undiagnosed, persistent, dominant mass without consideration of the mammogram. PMID- 3334961 TI - Relationship between mammographic and histologic features of breast tissue in women with benign biopsies. AB - Mammograms and histologic slides of a group of 320 women who had breast symptoms and a biopsy without cancer being found were reviewed. The mammographic features assessed were the parenchymal pattern and extent of nodular and homogeneous densities. In addition to the pathologic diagnosis, the histologic features assessed included epithelial hyperplasia and atypia, intralobular fibrosis, and extralobular fibrosis. Among premenopausal women, those with marked intralobular fibrosis were more likely to have large (3+ mm) nodular densities on the mammogram. Among postmenopausal women, epithelial hyperplasia or atypia was related to having nodular densities in at least 40% of the breast volume. In both groups, marked extralobular fibrosis was related to the presence of homogeneous density on the mammogram. We conclude that mammographic nodular densities may be an expression of lobular characteristics, whereas homogeneous density may reflect extralobular connective tissue changes. PMID- 3334963 TI - Transvaginal parametrial needle biopsy for detection of postirradiation recurrent cancer of the cervix. AB - During the 27-year period from 1956 to 1982, transvaginal parametrial needle biopsies were performed on 76 patients clinically suspected of harboring postirradiation recurrent cervical cancer without mucosal lesions suitable for biopsy under direct vision. Needle biopsies indicated cancer in 41 patients, resulting in 20 abdominal explorations. Eleven of these patients underwent total pelvic exenteration. Three patients survived longer than 5 years. Among 35 patients whose biopsies did not suggest cancer, eight proved to be false-negative as demonstrated by later progression of local and systemic disease. The remaining 27 patients in whom biopsies showed negative results were cured by radiation therapy. Bleeding, easily controlled by vaginal packing, occurred in one patient; in another, a pelvic abscess was drained 7 days after the biopsy. The authors conclude that when judiciously performed, transvaginal parametrial needle biopsy has a high diagnostic yield (89%) with minimal morbidity (2.6%). Its application during the careful observation of patients suspected to harbor recurrence may increase the operability rate and may offer selected patients a chance for cure by radical pelvic surgery. PMID- 3334962 TI - Gallium-67 scanning for malignant melanoma. AB - Melanoma is characterized by a tendency to metastasize widely throughout the body and its relative affinity for gallium-67. Because of the ability of this nuclide to image tumor sites in numerous organ systems, it has been used to detect metastases in patients with malignant melanoma. The effectiveness of this technique, however, has been controversial. This article documents the retrospective analysis of results from 296 gallium-67 scintiscans from 222 patients with melanoma. Patients were placed in two groups. The low suspicion group (148 patients undergoing 191 scans) consisted of patients with no evidence of disease; the gallium scans were performed solely for screening purposes. There were 175 true-negative scans, nine true-positive scans (eight of the nine were positive only at the untreated primary site), three false-negative scans, and four false-positive scans. Therefore, in only one patient (0.5%) did a "screening" gallium scan reveal disease that was not expected. The high suspicion group (85 patients undergoing 105 scans) consisted of patients with established evidence of metastatic disease; the gallium scan was performed to confirm those findings and to search for involvement of other organ systems. Of these scans, ten were true-negative, 73 true-positive, 21 false-negative, and one false positive. In this group the 20% false-negative results indicate that gallium scanning is considerably less sensitive than the combination of clinical and standard radiographic assessment. It was concluded that gallium-67 scintiscanning of patients with melanoma, whether for screening or evaluation of patients with known metastases, provides little information that affects clinical staging or therapeutic design. Therefore, the technique is of limited value for routinely investigating the extent of disease. PMID- 3334964 TI - Lymphocyte subsets in human thymoma studied with monoclonal antibodies. AB - Lymphocyte subsets were investigated using OKT series monoclonal antibodies and flowcytometry in 16 cases of thymoma. From the viewpoint of lymphocyte subsets, thymoma could be divided into three types: thymus lymphocyte type, peripheral lymphocyte type, and intermediate type. In thymus lymphocyte type, the number of OKT-6+ cells exceed that of OKT-3+ cells, and are more than 50%. In peripheral lymphocyte type, the number of OKT-6+ cells are less than that of OKT-3+ cells and less than 10%. In intermediate type, OKT-6+ cells are between 10% and 30%. These three types correlate well with the histologic features with respect to the number and distribution of lymphocytes in thymoma tissue. Lymphocytes were infiltrating abundantly and intermingled in the tumor cell nests in thymus lymphocyte type, and were infiltrating rather scantly and outside the nests in peripheral lymphocyte type. PMID- 3334965 TI - Different antitumor mechanisms of interferon-alpha in the treatment of hairy cell leukemia and renal cell cancer. AB - There is increasing evidence for the therapeutic effectiveness of Interferon alpha (IFN-alpha) in malignant diseases. However, the antitumor mechanisms of IFN alpha are not known. Using two examples, hairy Cell leukemia (HCL) and renal cell cancer (RCC), it is shown that the requirements for successful IFN-alpha therapy of HCL and RCC are different. In HCL low doses of IFN-alpha are sufficient to treat the disease. The reduction of hairy cells in peripheral blood is detectable within the first week of treatment. The endogenous IFN-alpha production in these patients is impaired as demonstrated by the lack of IFN-alpha induction and by low levels of 2-5 oligoadenylate synthetase in peripheral blood mononuclear cells. A possible reason for deficient endogenous IFN-alpha production is the lack of monocytes in HCL patients. It is likely that therapy with low doses of IFN-alpha substitutes for the endogenous IFN-alpha deficiency. In RCC comparatively high doses of IFN-alpha are necessary for a clinical response. There may be differences between the effectiveness of natural and recombinant alpha interferons. High doses given within a week seem to be more important than high single doses, which therefore suggests the need of daily treatment. Responses of RCC to IFN-alpha therapy are usually seen several months after the beginning of therapy. These differences in the effectiveness of IFN-alpha therapy for HCL and RCC suggest that IFN-alpha acts differently in the treatment of each disease. PMID- 3334966 TI - Prognostic value of histologic and clinical factors in 56 patients with gastrointestinal lymphomas. AB - To investigate the prognostic value of histologic and clinical factors in lymphomas of the gastrointestinal (GI) tract, the clinicopathologic findings in 56 Japanese patients with GI lymphomas were reviewed. They included 37 patients with gastric and 19 with intestinal lymphomas. The male to female ratio was 2.7:1 in gastric and 11:1 in small intestinal lymphomas. Histologically, all but one of intestinal lymphomas were high-grade lymphomas. Gastric lymphomas comprised 47% of low-grade and 53% of high-grade tumors. Significant factors for favorable prognosis identified by Cox's multivariate analysis were female sex, the presence of reactive lymphoid hyperplasia (RLH) in the primary site, early stage of disease, gastric lymphomas, and low-grade histologic type. The important role of chronic lymphocytic infiltration for development of gastric lymphoma was suggested by the high incidence of RLH and the intermediate lymphocytic type of lymphoma. PMID- 3334967 TI - Primary carcinoma of the small intestine. A clinicopathologic and immunohistochemical study. AB - A clinicopathologic and immunohistochemical study of fifty-two primary carcinomas of the small intestine (20 duodenal, 18 jejunal, and 14 ileal) was performed. Most of these neoplasms were located in the proximal duodenum, proximal jejunum, and distal ileum. Most of these tumors produced both sialomucin and sulfomucin, although the adjacent mucosa showed hyperplastic changes with increased sialomucin secretion. Argyrophil cells were recognized in seven duodenal (35%), 13 jejunal (72%), and nine ileal (69%) carcinomas. Eighteen of the 29 tumors showing positive argyrophil reactions also had argentaffin cells. The common features of mucins and endocrine cells in these tumors suggest the multipotency of small intestinal carcinoma. The prognosis correlated with the histologic type, carcinoembryonic antigen (CEA) grading, invading pattern of tumor margins, and vascular permeation and regional lymph node metastasis. PMID- 3334968 TI - Prognostic significance of DNA index, multiploidy, and S-phase fraction in ovarian cancer. AB - Paraffin-embedded tumor samples from 157 ovarian cancer patients were analyzed by DNA flow cytometry. Tumor ploidy had prognostic significance in both early and advanced ovarian cancer. After adjusting for stage, residual tumor mass, histopathologic type, treatment, and age of patient in a Cox regression analysis, the relative risk of death was two-fold higher in single DNA-aneuploid and sixfold higher in DNA-multiploid tumors as compared to DNA-diploid tumors (P less than 0.0001). A tetraploid DNA index was associated with a relatively low risk ratio, whereas hypertetraploid tumors were highly malignant. S-phase fraction (SPF) had prognostic value especially in DNA-diploid tumors. The simultaneous evaluation of DNA index, the number of aneuploid cell clones, and SPF gave more prognostic information than the determination of tumor ploidy alone. On the basis of these parameters we have developed a classification of tumor DNA histograms for better prognostic assessment of ovarian cancer. PMID- 3334969 TI - Ovarian mullerian mucinous papillary cystadenomas of borderline malignancy. A clinicopathologic analysis. AB - Ovarian mucinous cystadenomas of borderline malignancy that contain foci of intestinal differentiation are well recognized. Borderline tumors lined by mucinous epithelium of endocervical type and characterized by papillae architecturally similar to those of serous borderline tumors, however, have not been described in the literature. We have studied 30 tumors of this type. The patients averaged 34 years of age. Forty percent of the tumors were synchronously bilateral and 30% were associated with endometriosis. Four tumors were complicated by peritoneal implants, one by both peritoneal implants and lymph node metastasis and one by lymph node metastasis alone. No patient had pseudomyxoma peritonei. Follow-up information was available on all the patients for a mean interval of 3.7 years. In two cases tumors developed in the conserved contralateral ovary; no deaths occurred. These tumors have important clinical and pathologic differences from mucinous borderline tumors with intestinal differentiation, but have many similarities to mixed-epithelial borderline tumors of Mullerian type. PMID- 3334970 TI - Malignant peripheral neuroectodermal tumors. A retrospective analysis of 42 patients. AB - The clinical presentation of the disease and the results of treatment in 42 patients with malignant peripheral neuroectodermal tumors (MPNT) entered into the Cooperative Ewing's, soft tissue, and neuroblastoma trials of the German Society of Pediatric Oncology were retrospectively analyzed. Within the Ewing's sarcoma trial, patients with chest wall lesions were particularly analysed for MPNT features. The period of observation ranged from 15 to 86 months; the median relapse-free time was 24 months. There were 28 male and 14 female patients, the median age of patients was 15 years (range, 9 months-23 years). Thirty-two patients had localized disease (M0), and ten patients presented with primary metastases (M1). The predominant location of the tumors was the thoracopulmonary region, followed by the extremities, the abdominal/pelvic, and head and neck region. Thirty-one of 42 tumors involved the adjacent bone. The disease-free survival according to Kaplan-Meier life-table analysis was 56% +/- 11% for Stage M0 patients at 3 years. Nine of ten patients with M1 disease showed progression of their disease. Most patients had combined modality treatment with surgery, chemotherapy and radiation therapy. Best results were obtained with extensive surgery. Radiation doses ranged from 20 to 60 Gy and could not be correlated with the outcome of the disease. Most recurrences occurred at the site of the primary tumor. In patients with primary chemotherapy after biopsy-proven diagnosis, the responsiveness of this disease to chemotherapy could be demonstrated. Combination chemotherapy containing anthracyclines and high doses of alkylating agents appeared superior. PMID- 3334971 TI - Melanosomal alterations in dysplastic melanocytic nevi. A quantitative, ultrastructural investigation. AB - Abnormal-looking melanosomes are observed commonly in both intraepidermal melanocytes of cutaneous melanoma and dysplastic melanocytic nevi (DMN). This was investigated by using transmission electron microscopic examination to determine the percentage of abnormal melanosomes among 8267 melanosomes assessed in at least five solitary intraepidermal basal unit melanocytes from each of five specimens of DMN, superficial spreading melanoma (SSM), common acquired nevomelanocytic nevi (NMN), and normal skin (NS) adjacent to DMN. The percentage of abnormal melanosomes in DMN (mean + SD, 44 + 23%) was seven times greater than that in NMN (6 + 7%) and 22 times greater than that in NS (2 + 5% [P less than 0.001, both comparisons]), but only 80% that in SSM (57 + 19% [P less than 0.02]). Melanocyte area, nuclear area, and the ratio of nuclear area to cytoplasmic area did not account for the observed differences. Melanosomal alterations may be a useful marker of atypicality in melanocytic tumors. PMID- 3334972 TI - An experience with an implanted port system in 66 children with cancer. AB - Totally implanted port catheter systems have a lower incidence of infection and are more easily used in home care that external catheters in adult cancer patients. Experience with this method in children has been limited. During the past 2 years, we have implanted 71 ports in 66 children with cancer. Our experience demonstrates an infection rate (0.15 episodes of bacteremia per 100 patient days) slightly lower than that reported for children with Broviac or Hickman catheters, but not as low as that seen in adults with implanted systems. Patients and families have been extremely satisfied with the devices. Our experience supports further use of implanted systems in children with cancer. PMID- 3334973 TI - Nonpharmacologic factors in the development of posttreatment nausea with adjuvant chemotherapy for breast cancer. AB - A prospective, longitudinal design was used to determine the role of nonpharmacologic factors in the development of posttreatment nausea (PTN). Forty five women with no previous chemotherapy experience who were receiving a single regimen of adjuvant chemotherapy for breast cancer were interviewed before and after their first six infusions. Seventy-one percent of patients developed PTN. The PTN was related to the following: patients' physical status at the onset of treatment; heightened anxiety during infusions; susceptibility to nausea and vomiting after eating certain foods; and expectations of developing chemotherapy related nausea. Anxiety during infusions, susceptibility to nausea and vomiting, and expectations of side effects also accounted for differences in the frequency, intensity, and severity of PTN. These findings offer strong support for the view that nonpharmacologic factors contribute to individual differences in gastrointestinal responses to chemotherapy. PMID- 3334974 TI - Risk of genitourinary malignancies after cancer of the prostate. AB - The risk of second malignancies was evaluated in all men in metropolitan Atlanta who were initially diagnosed as having prostate cancer between January 1, 1975 and December 31, 1982. The cohort of 3675 men was observed through the end of calendar year 1984, yielding a total of 11,916 man-years of observation. Within this population 220 second cancers were diagnosed at sites other than the prostate as compared with 181.2 cancers expected based upon incidence rates for the local general population. Excesses of second malignancies were found in the urethra, kidney and bladder, as well as for melanoma of the skin. The increased risk of second neoplasms was generally greater in men younger than 70. The associated genitourinary malignancies tended to occur within 3 years of the prostatic cancer. Although increased clinical surveillance of this population could explain some of the observed excess of second cancers, these findings also are consistent with multiple cancers arising from shared etiologic factors. PMID- 3334975 TI - Smoking and bladder cancer. The modifying effect of cigarettes on other factors. AB - A population-based, incidence case-control study was used to assess the effect of cigarette smoking on other risk factors for the development of bladder cancer. White men (n = 332) between the ages of 21 and 84 with bladder cancer were compared with 686 population-based controls. Cigarette smokers were classified by current smoking status as well as by amount, duration, inhalation patterns, age at first having smoked, and years since having stopped smoking. These variables were associated with a change in the risk for bladder cancer. The population attributable risk associated with cigarette smoking was 48.5%. Risks from the use of other tobacco products such as cigars, pipes, snuff, and chewing tobacco, and from caffeinated coffee, tea, and alcoholic beverages were evaluated in light of cigarette smoking status. Cigarette smoking was shown to be both a confounder and an effect modifier. Risk estimates for bladder cancer associated with caffeinated coffee and alcoholic beverages were decreased after controlling for the effects of cigarette smoking. However, an increased risk of developing bladder cancer from cigar smoking (Odds ratio [OR] = 2.46) and tea drinking (OR = 3.14) was only seen in men who never smoked cigarettes. An increased but not significant risk was also seen for pipe, snuff, and chewing tobacco use in noncigarette smokers. The population-attributable risk from cigars and tea in the population of white men who had never smoked was 6.3% and 18.9%, respectively. Our results suggest that cigarette smoking may obscure other risk factors unless those who never smoked are separately studied. PMID- 3334977 TI - Women: targets of a tobacco industry under pressure. PMID- 3334976 TI - Spermatocytic seminoma with associated sarcoma of the testis. AB - Spermatocytic seminoma is a clinical pathologic distinct entity that has a good prognosis and rarely is associated with other neoplastic elements. Two cases of testicular spermatocytic seminoma with a sarcomatous element are reported. Both patients were older than 40 years and presented with 1-year and 2-year histories of progressive testicular enlargement and recent onset of testicular pain. Histologically, the spermatocytic seminoma in both cases consisted of three distinct cell types as has been previously described. Ultrastructurally, one case showed crystalloid structures similar to the Lubarsch's crystalloids described in spermatogonia of human testis. The sarcomatous component in one case was a rhabdomyosarcoma confirmed by light and by electron microscopic study whereas the second case was a primitive mesenchymal spindle cell sarcoma. Only the sarcomatous element metastasized; metastatic sites included lung and paraaortic lymph nodes in the first patient and lung and liver in the second. Despite aggressive treatment with combined surgery and multiagent chemotherapy, the first patient died within 1 year of diagnosis and the second at 14 months. PMID- 3334978 TI - Successful smoking cessation. PMID- 3334980 TI - Brain death and critical care nurses. PMID- 3334979 TI - The role of health professionals in organ donation. PMID- 3334981 TI - Brain stem death: managing the family in crisis. PMID- 3334982 TI - [Measurement of peak expiratory flow rate in patients with obstructive lung disease]. PMID- 3334983 TI - [Lupus erythematosus]. PMID- 3334984 TI - Translocation (7;21) in a lipoma. AB - Cytogenetic analysis was performed on a solitary lipoma from the flank of a 38 year-old male. A translocation t(7;21)(p22;q11.2) was found as the sole clonal chromosomal abnormality. The results are discussed in relation to other cytogenetic abnormalities found in benign adipose tumors. PMID- 3334985 TI - DNA ligase I, Bloom's syndrome, and cancer. PMID- 3334986 TI - In vitro pharmacodynamics of 1-beta-D-arabinofuranosylcytosine: synergy of antitumor activity with cis-diamminedichloroplatinum(II). AB - 1-beta-D-Arabinofuranosylcytosine (ara-C) was tested at a concentration of 10 micrograms/ml in the human tumor colony-forming assay against 55 human tumors of various histological types. Using the criterion for sensitivity of at least 70% inhibition of colony formation, 12 tumors (22%) were sensitive to ara-C. ara-C was most active against lung tumors (3 of 8 tumors were sensitive), and melanomas (6 of 8 sensitive). However, ara-C was not active against breast cancer (0 of 7) or colon cancer (0 of 3), and only 1 of 13 ovarian cancers was sensitive to ara C. The activity of ara-C against melanoma and other solid tumors was confirmed using a thymidine incorporation assay. The time (t) and concentration (C) dependency of the cytotoxicity of ara-C and other chemotherapeutic agents was determined. Most agents such as Adriamycin, cis-diamminedichloroplatinum(II) (cis platinum), and bleomycin were found to follow the C x t rule. That is, as the drug concentration was doubled, an equivalent amount of cell kill was achieved in half the time. However, the activity of ara-C was more concentration dependent than time dependent. ara-C was more effective when cells were exposed to high concentrations for short time periods. Synergy of activity between ara-C and cis platinum was demonstrated in the breast 231 and melanoma M19 cell lines. No synergy of interaction between these two drugs was observed in the colon HT29 and lung P3 cell lines. When fresh biopsy specimens were tested with the combination, there was evidence of a synergistic interaction in 9 of 36 (25%). Maximum cytotoxicity was obtained when cells were exposed to ara-C 2 h before the addition of cis-platinum. The addition of cis-platinum before ara-C decreased the synergism. PMID- 3334988 TI - Nonrandom chromosome alterations in human malignant mesothelioma. AB - Malignant mesothelioma (MM) is a neoplasm closely associated with asbestos exposure, which has been implicated in 70-80% of the cases. In this study, nine MM (two fresh surgical specimens, two permanent cell lines, and five xenografts in nude mice) were examined cytogenetically. Six patients had a known history of asbestos exposure. Seven MM were chromosomally abnormal, the majority having complex structural alterations affecting different chromosomes, whereas two fresh surgical specimens had a normal chromosome constitution. Alterations of chromosome 3 were detected in seven cases and changes involving chromosomes 1 and 7 were observed in six cases. The breakpoints of translocations and deletions on chromosome 1 involved several bands; however, 50% of the breakpoints were near the locations of Blym, L-myc, and ski protooncogenes. Forty % of the breaks on chromosome 7 involved bands q11.1-11.2 and 20% were at q22, the location of the met protooncogene. Nonrandom changes on chromosome 3 were interstitial or terminal deletions, and translocations involving the region p14-21. The deleted 3p segment was identifiable as part of a chromosome translocation in one MM and was apparently lost in the other six. The deletions involving 3p are either spontaneous or asbestos-induced lesions at vulnerable genomic sites and are the most common and nonrandom chromosome alterations observed. Possibly 3p abnormalities are causally related to the development of this malignancy. PMID- 3334987 TI - Interactions of putative estrogens with the intracellular receptor complex in mouse Leydig cells: relationship to preneoplastic hyperplasia. AB - The interaction of 14 steroidal and nonsteroidal estrogen agonists and antagonists with the intracellular estrogen receptor system was examined in cell suspensions prepared from the testes of mice that develop malignant Leydig cell tumors after prolonged estrogen administration. The ability of these substances to stimulate DNA synthesis in short-term (3-day) studies and to provoke Leydig cell hyperplasia with prolonged (3-mo) administration was also measured. Our data were consistent with the proposal that, in Leydig cells, the carcinogenic effects of estrogens are mediated through the intracellular receptor complex that results in a localization of hormone bound to chromatin and nuclear matrix. All tested compounds displaced 17 beta-[3H]estradiol from the cytosolic estrogen receptor, but to varying degrees; and there was no discernible relationship between their ability to compete for this receptor and their efficacy in stimulating DNA synthesis. The effect of the test compounds on the levels of estrogen receptor in cytosol and in nuclei was measured by [3H]estradiol exchange. 17 beta-Estradiol, equilin, 17 alpha-ethinylestradiol, diethylstilbestrol, hexestrol, dienestrol, coumestrol, and nafoxidine provoked a complete estrogen receptor response: acutely a decrease in the level of cytosolic estrogen receptor and an increase in the nuclear estrogen receptor. All of these substances acutely stimulated DNA synthesis. Tamoxifen, clomiphene, and nitromifene provoked a decrease in cytosolic receptor but no increase in demonstrable nuclear estrogen receptor. 17 alpha-Estradiol, mestranol, and estriol did not significantly alter the levels of estrogen receptor in cytosol or nuclei. Only those substances that increased measurable nuclear estrogen receptor also acutely stimulated DNA synthesis. Chronic (3-mo) treatment of 2-mo-old male BALB/c mice with diethylstilbestrol, 17 beta-estradiol, ethinylestradiol, and nafoxidine led to Leydig cell hyperplasia. Chronic mestranol treatment also provoked Leydig cell hyperplasia; this is most probably due to induction of liver metabolism of mestranol to ethinylestradiol. Chronic treatment with 17 alpha-estradiol, tamoxifen, and clomiphene failed to produce significant histologic al changes in the testes. Only chronic administration of those substances that exhibited a complete estrogen receptor response and acutely stimulated DNA synthesis produced Leydig cell hyperplasia. PMID- 3334989 TI - Mouse papillary lung tumors transplacentally induced by N-nitrosoethylurea: evidence for alveolar type II cell origin by comparative light microscopic, ultrastructural, and immunohistochemical studies. AB - A histogenetic study was designed to evaluate controversial findings on the cell of origin of tubular/papillary lung tumors in mice, i.e., bronchiolar Clara cell versus alveolar type II cell. N-Nitrosoethylurea (0.5 mmol or 0.74 mmol/kg) was given to pregnant C3H (C3H/HeNCr MTV-) and Swiss Webster [Tac:(SW)fBR] mice as a single i.p. injection on Day 14, 15, 16, or 18 of gestation. The offspring were studied at various ages ranging from 7 days to 52 wk. Serial sections of the whole lung (100 to 200 sections per mouse) showed that solid/alveolar and papillary tumors arose from the pulmonary acinus, invading the bronchioles only as the tumors grew. Furthermore, a mixture of solid and papillary patterns within a single module did not represent a merging of two tumors but a progression from the solid to the papillary form. By use of two rabbit antisera against mouse lung surfactant apoproteins found in normal alveolar type II cells, it was shown by the avidin-biotin peroxidase complex procedure, by the peroxidase-antiperoxidase technique, and by indirect immunofluorescence that both solid and papillary tumors contained these proteins that are specific markers for alveolar type II cells. With a rabbit anti-rat Clara cell antiserum, none of the tumors studied was immunoreactive while normal Clara cells were reactive. The nitroblue tetrazolium formazan stain for dehydrogenase enzymes, found particularly in Clara cells, did not reveal these enzymes in any lung tumors from either strain. Ultrastructurally, no typical features of the mature Clara cell were detected in papillary or other pulmonary neoplasms. However, all tumors showed characteristic alveolar type II cell structures such as various stages of lamellar body formation, although these features were less well differentiated in the papillary tumors. Argentaffin dense bodies, representing lysosomes and immature forms of lamellar bodies, were commonly observed in papillary tumors. Some features of the papillary tumors such as cell shape, high glycogen content, and primary cilia were equivalent to those seen in pulmonary epithelial precursor cells during fetal development. With age, the papillary tumors became invasive, accumulated neutral lipids, and developed bizarre cleaved nuclei and lamellated nuclear pseudoinclusions. In conclusion, the papillary lung tumors of the mouse, at least those induced transplacentally by N-nitrosoethylurea, constitute less well differentiated or poorly differentiated alveolar type II cell adenomas or carcinomas with fetal morphological and biochemical properties. PMID- 3334990 TI - Amplified and overexpressed epidermal growth factor receptor gene in uncultured primary human breast carcinoma. AB - We analyzed the epidermal growth factor receptor gene using a complementary DNA probe of the epidermal growth factor receptor gene in 21 uncultured primary breast carcinomas and found that the gene was amplified in three of these tumors. We further demonstrated by immunohistochemistry using a monoclonal antibody to the epidermal growth factor receptor that the receptor protein product of this gene was overexpressed and displayed elevated kinase activity. Our data indicate that one of the molecular mechanisms for overexpression of epidermal growth factor receptor in human breast cancer is epidermal growth factor receptor gene amplification without rearrangement in a subset of tumors. PMID- 3334991 TI - Induction of S 100 protein by 5-bromo-2'-deoxyuridine in human neuroblastoma cell lines. AB - The simultaneous effect of 5-bromo-2'-deoxyuridine (BrdUrd) on cell growth, morphological changes, and cellular contents of S 100 (S 100ao and S 100b) protein and neuron specific enolase was investigated in human neuroblastoma cells in culture. Among four cell lines (NCG, SK-N-DZ, GOTO, NB-1), GOTO was the most affected. With 5 micrograms/ml BrdUrd, the growth of this cell line was significantly inhibited to 14.5% of the control on day 6, in association with morphological changes into flat-type cells and an increase of S 100 protein. S 100ao protein was increased from 37 to 211,000 pg/mg protein (5,600-fold) and S 100b protein from less than 25 to 623 pg/mg protein. The induction of S 100 protein was also seen in SK-N-DZ but not in NCG and NB-1. In GOTO the induction of S 100 protein occurred in a dose- and time-dependent manner by the treatment with BrdUrd. On the other hand, after exposure to BrdUrd, neuron specific enolase decreased in NB-1 and SK-N-DZ and increased in GOTO. These results suggest that although heterogeneous certain neuroblastoma cell lines could be differentiated into S 100 protein-positive cells that may represent glial or Schwann cells and that the effect of BrdUrd is exerted bidirectionally in neuroblastoma differentiation. PMID- 3334992 TI - Chromosome abnormalities in pediatric brain tumors. AB - Recurrent, site-specific chromosome translocations and other cytogenetic abnormalities are being described in ever-increasing numbers and types of human tumors. Primary brain tumors are the most common pediatric solid tumor and differ from those of adults in both histology and clinical behavior. We examined chromosomes from 21 primary pediatric brain neoplasms grown in short-term tissue culture, including 6 astrocytomas, 10 primitive neuroectodermal tumors, and 5 other tumors. Karyotypes from 3 of 5 astrocytomas were abnormal, as were those of 9 of 10 primitive neuroectodermal tumors. Numerical abnormalities were found in 6 tumors and structural aberrations in 12 tumors. Deletions, additions, and translocations involving the short arm of chromosome 1 were observed in 5 tumors, with chromosome breakpoints ranging from 1p1 to 1p3. An isochromosome of the long arm of 17, i(17q) was the most frequent site-specific structural abnormality, found in 1 anaplastic astrocytoma and 2 recurrent cerebellar primitive neuroectodermal tumors, one with islands of anaplastic astrocytoma. These results differ from reported chromosome studies of adult brain tumors, suggesting that pediatric brain tumors may differ from those of adults when examined at the genetic level. Additional chromosomal and molecular studies of brain tumors from children are warranted to define these differences. PMID- 3334993 TI - Correlation of vascular permeability and blood flow with monoclonal antibody uptake by human Clouser and renal cell xenografts. AB - The specific uptake of 125I-A6H antibody by xenografts of the human renal cell carcinoma (RCC) TK177G in the athymic mouse was considerably greater than that seen for other human tumor xenografts and their associated antibodies (e.g., 125I B6.2 uptake by the human breast carcinoma, Clouser). In addition the A6H-RCC model also demonstrated both greater localization indices and absolute amount of antibody bound than did the B6.2-Clouser model. Several physiological factors were studied to assess whether they might play a role in this greater specific uptake. Vascular volume was determined using the in situ labeling of red blood cells with 99mTc. Vascular permeability was determined by measuring the amount of 125I-labeled bovine serum albumin and 131I-labeled nonspecific IgG1 (anti horseradish peroxidase) extravasated out of the tumor vasculature during 1 hr. Relative blood flow to the tumor was determined using the 86Rb method. Blood flow and vascular permeability were found to be significantly greater in the RCC tumor xenografts than in Clouser tumors. Differences in vascular permeability were especially dramatic, showing the vasculature of the RCC xenograft was twice as permeable as that of the Clouser tumor. Animals bearing either RCC or Clouser xenografts were injected with a monoclonal antibody to human major histocompatibility complexes (125I-labeled anti-human histocompatibility complex A, B, C). Tumor uptake of 125I-labeled anti-human histocompatibility complex A, B, C was found to be 5 times greater in RCC than Clouser xenografts. These results, therefore, suggest that the differences seen in the physiological factors studied can account for some of the greater specific 125I-A6H uptake by the RCC tumor than 125I-B6.2 uptake by the Clouser xenograft. PMID- 3334994 TI - Effect of D,L-buthionine-S,R-sulfoximine on cytotoxicity and DNA cross-linking induced by bifunctional DNA-reactive cytostatic drugs in human melanoma cells. AB - The effects of D,L-buthionine-S,R-sulfoximine (BSO) on cytotoxicity and DNA cross linking induced by bifunctional DNA-reactive cytostatic agents in a human melanoma cell line (RPMI 8322) were investigated. RPMI 8322 cells were exposed to 0.01 mM BSO for 24 h, which resulted in a decrease in cellular glutathione to 14% without any reduction of cell proliferation or plating efficiency. BSO pretreatment significantly enhanced cytotoxicity of melphalan with a dose modification factor (DMF) of 3.4 and nitrogen mustard (HN2) (DMF 3.3). The increased cytotoxicity was paralleled by similar increases in DNA cross-linking (melphalan: DMF 2.2, HN2: DNF 2.5). A small but significant potentiation by BSO of cis-diamminedichloroplatinum(II) toxicity was seen (DMF 1.5), with a corresponding minor but significant increase in DNA cross-linking (DMF 1.1). Similarly, the potentiation of bis-chloroethylnitrosurea toxicity was small but significant (DMF 1.1), with no significant increase in DNA cross-linking (DMF 1.0). No effect of BSO pretreatment on the rate of removal of HN2-induced DNA cross-links was observed. Thus, the observed sensitization of RPMI 8322 cells to melphalan, HN2, cis-diamminedichloroplatinum(II), and bis-chloroethylnitrosourea was correlated to similar changes in drug-induced DNA cross-linking. Despite the increased cytotoxicity and DNA cross-linking BSO did not significantly increase the intracellular concentration of intact melphalan. These findings support the hypothesis that the potentiation of the cytotoxicity of bifunctional alkylating agents by BSO is due to an increased DNA cross-linking caused by a reduced intracellular conjugation of drug with glutathione, which results in an increased binding of drug to DNA targets. PMID- 3334995 TI - New photosensitizers for photodynamic therapy: combined effect of metallopurpurin derivatives and light on transplantable bladder tumors. AB - A series of metallopurpurins was tested for their photodynamic activity against transplantable N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide-induced urothelial tumors growing in male Fischer CDF (F344/CrlBR) rats. Histological examination of tumors in animals treated with the metallopurpurins and red light (greater than 590 nm, 360 J/cm2) revealed tumor necrosis 24 h after completion of therapy. Control tumors showed no histological change. In 30-day tumor regrowth studies, 70% of animals treated with the metallopurpurin derivative SnET2 were free of tumors while 50% of the animals treated with the free-base purpurin ET2 were free of tumor. Metallopurpurins have intense absorptions in the red region of the visible spectrum, a region with good tissue penetration. The metallopurpurins are easily prepared from the corresponding purpurins with a high degree of purity. This study demonstrates the potential of these photosensitizers for photodynamic cancer therapy. PMID- 3334996 TI - Pharmacokinetics of intraperitoneally administered dipyridamole in cancer patients. AB - The pharmacokinetics of i.p. administered dipyridamole was studied in six patients to explore the feasibility of using this drug as a modulator of antimetabolite activity in extravascular spaces. Infusions of dipyridamole (50 mg/m2 in 2 liters of normal saline) into the peritoneal cavity resulted in peak drug concentrations 5 to 20 times higher in that cavity than in the plasma. The peritoneal decay data for dipyridamole fitted very well to a single compartment open pharmacokinetic model with one exponential term, while the plasma data are adequately described by a single compartment model with two exponentials (a short absorption phase). The mean peritoneal half-life for total extractable dipyridamole was 3.3 +/- 1.9 (SD) h, and the mean peritoneal clearance was 0.4 +/ 0.3 liters/h/m2. The mean plasma half-life of total dipyridamole in our patients was 2.2 +/- 1.2 h, and the mean clearance value was 5.7 +/- 4.7 liters/h/m2. The area under the concentration versus time curve was calculated to be 626 +/- 312 microM-h for the peritoneal cavity and 45 +/- 20 microM-h for the plasma. Using membrane ultrafiltration, we have measured the concentration of free (non-protein bound) dipyridamole in each patient. While the peritoneal clearance values of free and total drug are comparable, the plasma clearance of free dipyridamole was 47 +/- 39 liters/h/m2. This increased plasma clearance resulted in a plasma area under the concentration versus time curve of 8.3 +/- 5.1 microM-h, which suggests minimal systemic exposure. Our data show that instillation of dipyridamole into the peritoneal cavity resulted in much higher local drug exposure than systemic exposure, confirming the feasibility of using this drug to augment antimetabolite activity within the peritoneal cavity. Since dipyridamole is highly protein bound in the plasma but less so in the peritoneal cavity, these data imply that peritoneal exposure to active (free) dipyridamole is far greater than systemic exposure in our patients. PMID- 3334997 TI - Sister chromatid exchange induction by diaziquone in human and mouse lymphocytes following both in vivo and in vitro exposures. AB - Diaziquone (AZQ) (NSC 182986), a lipid-soluble benzoquinone derivative currently being tested as an experimental chemotherapeutic agent, was used to treat mouse and human peripheral blood lymphocytes (PBLs) to determine its genotoxic potential by examination of sister chromatid exchange (SCE) induction. In vitro exposure to AZQ caused a linear increase in SCE in both mouse and human PBLs, with mouse PBLs being about twice as sensitive as the human cells. The lowest in vitro concentration found to induce a significant effect on SCE frequency was 0.3 micrograms/ml in mice and 1.0 micrograms/ml in human PBLs. Mice exposed by either i.p. or i.v. injection showed similar dose-related linear increases in SCE frequencies in their PBLs. After i.v. administration of AZQ, splenocytes from treated mice showed approximately the same SCE frequency as found in the PBLs. In general, AZQ caused a slowing of cell cycling in vivo while giving inconsistent responses in vitro. AZQ did cause a dose-related decrease in the number of recoverable mononuclear lymphocytes in mice treated in vivo. Contrary to the in vitro studies, comparison of SCE responses in mice with those previously observed in brain tumor patients undergoing chemotherapy with AZQ (Kligerman et al., Cancer Res., 47: 631-635, 1987) revealed AZQ was a much more potent SCE inducer in humans than in mice. PMID- 3334998 TI - Mutagenicity of the antitumor antibiotic CC-1065 and its analogues in mammalian (V79) cells and bacteria. AB - CC-1065 is a very potent antitumor antibiotic which binds in the minor groove of DNA with alkylation at N-3 of adenine. Since CC-1065 caused delayed deaths in mice at therapeutic doses, analogues were prepared whose antitumor and biochemical activities have been reported. In this study, the mutagenicity for V79 cells (6-thioguanine resistance) and Salmonella (histidine auxotrophy or azaguanine resistance) of selected analogues was compared to DNA-binding activity and the structure-activity relationship was determined. CC-1065, U-62,736, U 66,866, U-66,694, U-67,786, and U-68,415 all have an A segment with an intact cyclopropyl group and different B segments. The cyclopropyl group is absent from U-66,226 and U-63,360. Elimination of the cyclopropyl ring diminished the cytotoxic and mutagenic potency of the compounds such that U-63,360 was nearly three orders of magnitude less potent than CC-1065 in V79 cells. For the compounds with an intact cyclopropyl group, the order of cytotoxic and mutagenic potency (molar basis) in V79 cells generally correlated with binding to calf thymus DNA, and increased with the length of the B segment. Thus, the order of cytotoxicity was CC-1065 greater than U-68,415 greater than U-66,694 greater than U-66,866 greater than U-62,736. U-67,786 fell outside this pattern since it was more cytotoxic and mutagenic than U-66,694, although it was of a similar size and had similar DNA-binding activity. These results show that an electrophilic carbon afforded by an intact cyclopropyl group of this type is necessary but not sufficient to account for the high cytotoxic and mutagenic potency of CC-1065 and U-68,415. The size and characteristics of the B segment also affect the potency. At an equitoxic (10 or 50% lethal dose) dose, an inverse relationship exists between cytotoxic and mutagenic potency such that at the 50% lethal dose, the least cytotoxic compound (U-62,736) was more mutagenic than the most cytotoxic compound (CC-1065). We speculate that the more cytotoxic analogues are less mutagenic (at an equitoxic dose) because they may have greater structure-directed binding to less mutable DNA sites in the minor groove. PMID- 3334999 TI - Genetic assessment of the strength of a cancer suppressor gene in hamster cells. AB - Tetraploid and near-tetraploid chemically transformed derivatives of the pseudodiploid hamster line BHK 21/clone 13 were prepared in four different ways and their ability to be suppressed for anchorage independence by fusion to the anchorage-dependent parental line was tested. In all cases the presence of a single normal genome, thought on genetic grounds to contain a single suppressor gene, was able to prevent the anchorage-independent growth of transformed lines whether they contained one or two complements of pseudodiploid chromosomes. Suppression of the single step in carcinogenesis that is registered by BHK cells as they transform to anchorage independence is thus unusually powerful and apparently independent of chromosome balance and of strict dosage effects. PMID- 3335000 TI - cis-Diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells. AB - We have characterized the accumulation of cisplatin (DDP) into parent and cisplatin-resistant 2008 human ovarian carcinoma cells. Accumulation of DDP at 1 h was a linear function of concentration from 0.25 to 100 microM DDP in both cell types. DDP-resistant cells that were only 3.3-fold resistant had approximately 50% less accumulated platinum at all concentrations examined. Accumulation of 1.0 microM DDP was linear for approximately 3 h and then slowed but did not reach equilibrium at up to 24 h in either cell type. The decreased DDP accumulation in resistant cells did not appear to be due to increased efflux; similar percentages of platinum were available for exodus in parent and resistant cells. Intracellular metabolites of DDP appeared to be decreased by similar amounts in the resistant cells. Native DDP was not driven uphill into cells against a concentration gradient, suggesting that DDP uptake does not involve primary active transport. The metabolic inhibitors, dinitrophenol and NaF, did not decrease DDP accumulation; iodoacetate had a stimulatory effect. Dinitrophenol, however, in combination with NaF or iodoacetate decreased DDP accumulation. A 30 min exposure to 0.2 mM ouabain also decreased DDP accumulation in both parent and resistant cells. A component of DDP accumulation thus appears to be energy dependent. These studies have identified decreased DDP accumulation as an important mechanism of resistance that is expressed early in the acquisition of DDP resistance in human ovarian carcinoma cells. PMID- 3335002 TI - Accumulation of cis-diamminedichloroplatinum(II) and platinum analogues by platinum-resistant murine leukemia cells in vitro. AB - Three murine leukemia lines resistant to cis-diamminedichloroplatinum(II) and one line resistant to diaminocyclohexane (DACH) platinum(II) complexes were compared to their platinum-sensitive parent lines to determine whether differences in net platinum accumulation were related to the resistant phenotype. The cis diamminedichloroplatinum(II)-resistant lines (L1210PtR4, L1210DDP5, P388PtR4) and the DACH-resistant line (L1210DACH) were incubated in vitro with cis diamminedichloroplatinum(II), [sp-4-2-(1R,2R)]-(1,2-cyclohexanediamine-N N')dichloroplatinum(II) , [sp-4-2-(1R,2R)]-(1,2-cyclohexanediamine-N N')[ethanedioato( 2-)- O,O']platinum(II), or diaminocyclobutanedicarboxylatoplatinum(II) and the time-dependent cellular platinum levels determined by flameless atomic absorption spectrophotometry. Cell lines resistant to a given platinum complex showed a reduction in the rate of platinum accumulation when compared to the sensitive line at 37 degrees C. Intracellular levels of diaminocyclobutanedicarboxylatoplatinum(II) were too low to confidently measure under the conditions of this study. Our data suggest that the mechanism of platinum resistance in these cell lines may be related to a reduced accumulation of the platinum-containing drug, although patterns of cross resistance suggest other mechanisms may be operative as well. PMID- 3335001 TI - 31P-nuclear magnetic resonance spectroscopy studies of the response of rat mammary tumors to endocrine therapy. AB - We have used 31P-nuclear magnetic resonance spectroscopy to detect the metabolic changes that occur in estrogen-sensitive, N-methyl-N-nitrosourea-induced rat mammary tumors as they regress following ovariectomy. In untreated animals the spectra of the tumors showed a steady loss of high energy phosphates (phosphocreatine and nucleoside triphosphates) and an increase in inorganic phosphate. This was reversed after ovariectomy. Spectral changes occurred before detectable regression of the tumor. Estrogen-insensitive tumors, grown from implanted Rama 600 and 622 cells, did not regress in response to ovariectomy, and their high energy phosphates continued to fall; estrogen-sensitive tumors also failed to respond to sham ovariectomy. These effects are probably due to the reduction in cellular energy requirements that occurs when the hormonal stimulus to growth is removed. Because the nuclear magnetic resonance method is noninvasive, this technique should be applicable clinically as a means of predicting the response of a tumor to endocrine therapy. PMID- 3335003 TI - Possible mechanism of Sudan III-induced prevention of chemical carcinogenesis in rats. AB - The effect of treatment of rats with Sudan III on the ability of the liver to transform benzo(a)pyrene (BP) to a mutagen was investigated to elucidate a possible mechanism of the Sudan III-induced prevention of chemical carcinogenesis (Huggins et al., Proc. Natl. Acad. Sci., 75:4524-4527, 1978) using a modified Ames mutagenesis test system. Preincubation of BP with liver 9000 x g supernatant (S-9) from rats treated with Sudan III markedly increased the mutagenicity of BP in the conventional Ames method. The increase in number of revertant colonies was proportional to the aryl hydrocarbon hydroxylase activity of the S-9 fractions used (r greater than 0.9). This azo dye was found to induce both cytochrome P-448 which is an activating enzyme of procarcinogens and the activities of UDP glucuronyl transferase and glutathione-S-transferase (GST), which are detoxifying enzymes of active carcinogenic intermediates. The addition of anti-cytochrome P 448 antibody or the cofactors for UDP glucuronyl transferase and glutathione-S transferase to the liver S-9 preincubation mixture with BP caused a marked decrease in BP mutagenicity when liver S-9 fractions from Sudan III-treated rats were used. The decrease obtained by the addition of the cofactors was proportional to the induced levels of the UDP glucuronyl transferase or glutathione-S-transferase. It was concluded that Sudan III-induced prevention of chemical carcinogenesis is due to an accelerated elimination of the carcinogen by the induction of both cytochrome P-448 and detoxifying enzymes with a limited increase in levels of active metabolic intermediates. PMID- 3335005 TI - Tumorigenicity of murine lymphomas selected through fluorescence-detected natural antibody binding. AB - Fluorescence-activated cell sorting was used to isolate high and low IgM natural antibody (NAb) binding populations from a heterogeneous line of the L5178Y-F9 murine lymphoma. The ranking of NAb binding and complement-dependent NAb lysis of the selected and starting lines were the same and opposite to that of their tumorigenicity in syngeneic DBA/2 mice. L5178Y-F9 and SL2-5 clones repeatedly treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and selected by fluorescence-activated cell sorting for high NAb binding exhibited increases in NAb binding and sensitivity to complement-dependent NAb lysis which corresponded with reduced tumor frequencies of threshold inocula. Although the high NAb binding SL2-5 line was slightly more sensitive to natural killer (NK) cell cytolysis, changes in susceptibility to activated macrophages or hypotonic lysis were not consistent with the observed reductions in tumor frequency so that the selected alterations in NAb binding corresponded best with tumorigenicity. These data confirm the same inverse relationship exhibited previously by in vivo and in vitro selected tumor variants and provide more precise evidence supporting a role for NAb in host resistance against tumor foci. PMID- 3335004 TI - Expression of endogenous retrovirus-like sequences and cellular oncogenes during phenobarbital treatment and regeneration in rat liver. AB - The expression of two cellular oncogenes (c-myc and c-Ha-ras), the epidermal growth factor receptor gene, and two endogenous retrovirus-like sequences (rat leukemia virus and 30S) was examined in control (nonregenerating) rat livers and at various times after partial hepatectomy. One group of rats had been fed phenobarbital (0.05%) for 16 days prior to the partial hepatectomy. The feeding of phenobarbital (0.05%) itself led to a 65% decrease in the level of epidermal growth factor receptor RNA, but no major change in the level of c-myc, H-ras, rat leukemia virus, or 30S RNAs, in the control rat livers. There was a considerable increase (4- to 5-fold) in the level of c-myc transcripts, at 12 and 48 h after partial hepatectomy in the phenobarbital-treated rats, and at 12 and 24 h in the rats on the control diet. By 72 h, the level of c-myc transcripts returned to normal in both groups of rats. A slight increase (about 1.5-fold) in the level of c-H-ras transcripts was seen at 24 h, which returned to normal levels by 168 h, in the regenerating livers of both the phenobarbital-treated and control diet rats. The regenerating livers displayed a marked decrease (3- to 4-fold) in the level of epidermal growth factor receptor RNA in both the phenobarbital and control diet rats. A marked increase (5- to 6-fold) in the level of transcripts homologous to the endogenous rat leukemia virus-like sequence was seen at 24 h in all of the regenerating livers, but there was no significant change in the level of RNAs homologous to 30S. Thus, the proliferation of normal rat liver cells mimics some but not all of the changes in mRNA levels that we have previously described in rat liver tumors. PMID- 3335007 TI - 1,N2-ethenodeoxyguanosine as a potential marker for DNA adduct formation by trans 4-hydroxy-2-nonenal. AB - The reaction of trans-4-hydroxy-2-nonenal, a major alpha, beta-unsaturated aldehyde released during lipid peroxidation, with deoxyguanosine under physiological conditions was investigated in order to assess its DNA damaging potential. This aldehyde was dissolved in tetrahydrofuran (THF) prior to addition to the reaction mixture. The results showed that structurally different adducts were formed in these reactions depending on the THF used. Using THF unprotected from light, reactions yielded adducts 1 to 6. Adduct 1 was characterized as 1,N2 ethenodeoxyguanosine (5,9-dihydro-9-oxo-3-beta-D-deoxyribofuranosylimidazo[1,2 alpha]pu rine) by its UV, proton nuclear magnetic resonance, and mass spectrum and by comparison to the corresponding guanosine and guanine adducts reported in the literature. The UV spectrum of adduct 4 was indicative of a substituted 1,N2 etheno derivative. Adducts 2,3,5, and 6 were essentially identical in UV spectra and appeared to be N2-substituted deoxyguanosine diastereomers. At room temperature adducts 2,3,5, and 6 were converted quantitatively to a single product at pH 10.5. This product was shown to be identical to 1,N2 ethenodeoxyguanosine (adduct 1). Analogous conversions to 1,N2-ethenoguanine were also observed for the corresponding guanine adducts. Using THF that had been protected from the light, however, the reactions of trans-4-hydroxy-2-nonenal with deoxyguanosine gave three major adducts, 7,8, and 9. These adducts possessed UV spectra similar to that of 1,N2-propanodeoxyguanosine and were not converted to 1,N2-ethenodeoxyguanosine upon base treatment. Evidence obtained suggests that adducts 1 to 6 were formed from the reaction of deoxyguanosine with the epoxide of trans-4-hydroxy-2-nonenal generated in the presence of hydroperoxide in the light unprotected THF, whereas adducts 7 to 9 were formed by direct Michael addition. Adducts 1 to 6 were formed presumably as a result of nucleophilic addition of the exo-amino of deoxyguanosine to the aldehydic group of the epoxide of trans-4-hydroxy-2-nonenal. Base treatment of these adducts facilitated subsequent cyclization and eliminations and finally gave 1,N2 ethenodeoxyguanosine. These results demonstrated that trans-4-hydroxy-2-nonenal readily forms adducts with deoxyguanosine either by direct Michael addition or via its epoxide formation. The facile conversion of some of these adducts to a single adduct suggests that 1,N2-ethenodeoxyguanosine may provide a simple and useful marker for assessing potential DNA damage by trans-4-hydroxy-2-nonenal and related alkenals associated with lipid peroxidation. PMID- 3335006 TI - Unexpected toxicity associated with use of body surface area for dosing melphalan in the dog. AB - A multiinstitutional Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was administered at 7.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater toxicity was observed in small dogs. Seven of the eight dogs (88%) weighing less than 14 kg experienced severe myelosuppression (neutropenia, less than 1500/mm3; and/or thrombocytopenia, less than 80,000/mm3), whereas only three of 13 dogs (23%) weighing greater than 14 kg developed severe myelosuppression (P = 0.016). We concluded that small dogs are at greater risk of developing bone marrow toxicity from i.v. melphalan than large dogs if body surface area is used to calculate the dose. Although both body surface area and weight were found to be significantly correlated with severity of toxicity, melphalan-induced toxicity in dogs can be more accurately estimated by body weight than by surface area, P = 0.008 versus P = 0.022, respectively. It may be necessary to prescribe antineoplastic agents that are eliminated by processes not primarily under metabolic influence or that produce side effects on tissue not correlated to basal metabolic rate on a parameter other than body surface area. In dogs, melphalan should be dosed on a weight basis, and treatment groups should be stratified by weight in randomized clinical studies, particularly when the weight range of treated subjects is great. PMID- 3335008 TI - Modulation of arabinosylnucleoside metabolism by arabinosylnucleotides in human leukemia cells. AB - Previous studies have indicated that deoxycytidine kinase (dCK) is requisite and rate limiting in the phosphorylation of 1-beta-D-arabinofuranosylcytosine (ara-C) and 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) on the pathway to their respective cytotoxic 5'-triphosphates. In K562 cells, the rate of triphosphate accumulation was maximal during incubation with 10 microM ara-C (35 microM/h) and 300 microM F-ara-A (102 microM/h). Under these conditions, accumulation of cellular ara-CTP plateaued at about 110 microM after 3 h, whereas in separate cultures, F-ara-ATP continued to accumulate at a linear rate to cellular concentrations greater than 500 microM after 5 h. Other laboratories have demonstrated that dCK activity in cell-free extracts was inhibited by ara-CTP. To determine whether ara-CTP exhibited the same activity in whole cells, K562 cells were preincubated with ara-C to accumulate 110 microM ara-CTP. After washing into medium containing F-ara-A, the rate of F-ara-ATP accumulation was significantly decreased (37 microM/h). However, cells loaded with F-ara-ATP exhibited an increased rate of ara-CTP accumulation (110 microM/h) that resulted in cellular ara-CTP concentrations in excess of 400 microM after 5 h. This stimulation was proportional to the cellular concentration of F-ara-ATP, achieving a maximum effect between 75 and 100 microM. Phosphorylation of ara-C by cell-free extracts supplemented with physiological levels of ribo- and deoxyribonucleoside 5' triphosphates was stimulated by addition of F-ara-ATP. The decreased rate of accumulation of products of dCK in intact cells containing 110 microM ara-CTP suggests that this active triphosphate may limit its own synthesis and phosphorylation of other substrates. In contrast, stimulation of the accumulation of ara-CTP in cells containing F-ara-ATP suggests new possibilities for the design of combination chemotherapy regimens. PMID- 3335009 TI - Role of metabolism and DNA adduct formation in the induction of sister chromatid exchanges in human lymphocytes by diethylstilbestrol. AB - Recent studies have shown that diethylstilbestrol (DES) induces sister chromatid exchanges (SCEs) in lymphocytes from pregnant and premenopausal women but has only a slight effect on lymphocytes from post-menopausal women or men. In this study blood specimens from premenopausal women were used to define the role of different metabolic pathways on DES-induced formation of SCEs and to determine whether conditions resulting in induction of SCEs also induced detectable levels of DNA adducts. Exposure of lymphocytes in vitro to 0-40 microM DES induced a concentration-dependent increase in SCEs. Addition of indomethacin to the cultures partially abolished DES-induced SCEs, suggesting involvement of prostaglandin synthetases in the formation of specific DES metabolites that cause SCEs. alpha-Naphthoflavone, an inhibitor of cytochrome P-450 monooxygenases, had no effect on DES-induced SCEs. Cells exposed to DES at doses sufficient to cause large increases in SCE induction did not have adducts detectable by a 32P postlabeling assay capable of revealing adducts at a level of 1 adduct/10(9) normal nucleotides. PMID- 3335010 TI - Effect of gestational development of lung tumor size and morphology in the mouse. AB - Pregnant C3HeB/FeJ mice were treated with ethylnitrosourea (ENU) on one of gestation Days 10, 13, or 15 to determine if ENU treatment at different stages of gestation would result in qualitative or quantitative differences in lung tumors induced in the offspring. Lung tumors were counted and measured 6 mo after treatment with ENU. Offspring of mice treated with ENU on Day 10 of gestation had a small increase in lung tumors while those treated on gestation Day 13 or 15 had significantly more tumors than controls and 6- to 8-fold more tumors than the treated mothers. An inverse relationship between age at the time of treatment and lung tumor size was found. The mean lung tumor volume of mice exposed on Day 10 of gestation was 167-fold larger than that of mice exposed to ENU as adults. The difference between mean lung tumor volume in mice which had been exposed to ENU on Day 10, 13, or 15 of gestation appeared to be associated with the exponential growth of the fetus during this period of gestation. Lung tumors induced on Days 10 and 13 of gestation were irregular in contour and were multinodular. Sixty five to 85% of the lung tumors in offspring treated during gestation versus 20% in mice treated as adults had a papillary morphology. These differences in tumor size and morphology indicate that cells transformed during early development may pose a greater biological hazard than cells transformed in older animals. PMID- 3335011 TI - Specific chromosomal abnormalities in malignant human gliomas. AB - Karyotypic analysis of 54 malignant human gliomas (5 anaplastic astrocytomas, 43 glioblastoma multiformes, 3 gliosarcomas, 2 giant cell glioblastomas, 1 anaplastic mixed glioma) has demonstrated that 12 tumors contained normal stemlines or only lacked one sex chromosome. The 42 tumors with abnormal karyotypes included 38 tumors which could be completely analyzed. Six of these 38 cases had near-triploid or near-tetraploid stemlines and 32 had near-diploid stemlines. Statistically significant numerical deviations in the near-diploid group were gains of chromosome 7 (26 of 32; P less than 0.001), and losses of chromosome 10 (19 of 32; P less than 0.001). Double minutes occurred in 18 of 32 near diploid tumors. The distribution of structural abnormalities was analyzed statistically by comparing the incidence of breakpoint in each chromosomal arm to the expected value based on chromosomal arm length. This analysis demonstrated that structural abnormalities of 9p and 19q were significant statistically (P less than 0.005 and P = 0.02, respectively). Although chromosome 1, 6p, the centromeric region of chromosome 11, 13q, and 15q were also frequently involved in structural abnormalities, the incidence of these breaks did not reach statistical significance. This demonstration of specific chromosomal abnormalities in near-diploid gliomas provides the basis for the investigation of genes which may be quantitatively or qualitatively altered in these neoplasms. PMID- 3335012 TI - Effect of cis-diamminedichloroplatinum(II) combined with whole body hyperthermia on renal injury. AB - The effect of whole body hyperthermia (WBH) on cis-diamminedichloroplatinum (II) (DDP) induced renal toxicity and antitumor effect was studied using a F344 rat model. Renal injury at 5 and 14 days after treatment was evaluated using animal mortality, renal functional assays (blood urea nitrogen, creatinine), and histopathological methods. WBH (120 min at 41.5 degrees C) enhanced both antitumor effects and toxic side effects. The latter included increased mortality, increased blood urea nitrogen and creatinine levels, and increased renal damage. After simultaneous treatment with WBH and DDP, thermal enhancement ratios (TER) for renal damage between 2.5 and 3.0 were calculated. The histopathological changes observed in the kidney after DDP alone or combined with WBH were primarily found in the proximal pars recta tubules (S3 segment) in the outer stripe of the outer medulla. There was no qualitative difference in tubular damage between rats treated with DDP alone or those treated with DDP combined with WBH. However, at a fixed DDP dose, damage in the combined treatment modality group was significantly greater than in the DDP-only treated group. PMID- 3335013 TI - Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. AB - We studied the relation of total serum cholesterol to all cancer and site specific cancer incidence in a cohort based on a probability sample of the United States population. A total of 5125 men (yielding 459 cancers) and 7363 women (398 cancers) were initially examined in 1971-75 and followed a median of 10 yr. An examination of age-adjusted incidence rates by cholesterol level showed an inverse association between cholesterol and all cancer; lung, colorectal, pancreatic, and bladder cancers; and leukemia. In women a weak inverse relation (reflecting an elevated rate among those only in the lowest cholesterol quintile) was apparent for all cancer; more prominent inverse associations were seen for cancers of the lung, pancreas, bladder, cervix, and for leukemia. A more detailed analysis of cholesterol and colorectal cancer revealed little association in both men and women. For an aggregate group of smoking-related cancers, the inverse relation was especially prominent: the multivariate relative risk estimates for subjects in the lowest cholesterol quintile, compared to those in the highest quintile, were 2.1 (1.1-3.8) and 3.3 (1.4-7.8) for men and women, respectively. The inverse association was present for smoking-related cancers diagnosed 6 or more yr after cholesterol determination in both men and women, suggesting that this association cannot be simply dismissed as a preclinical cancer effect. Further investigation of the cholesterol-cancer question, particularly the relation between cholesterol and smoking-related cancers, may provide useful etiological leads. PMID- 3335014 TI - Reevaluation of the maximum tolerated dose of continuous venous infusion of 5 fluorouracil with pharmacokinetics. AB - 5-Fluorouracil (5-FU) was administered as a continuous ambulatory venous infusion to 25 patients in a Phase I trial. The principal dose limiting toxic effect observed was mucositis. Skin rash and diarrhea occurred less frequently. Hematological toxicity was modest, and no hepatic toxicity was seen. One partial remission of 138 days duration was seen in a patient with metastatic breast carcinoma who was previously refractory to a 5-FU combination regimen. Patient tolerance of 5-FU delivered in this manner appeared highly variable. On the basis of this trial, we recommend that future studies evaluating the efficacy of long term venous infusion of 5-FU should utilize a dosage of 450 mg/m2/day. PMID- 3335015 TI - Lex and Ley antigen expression in human pancreatic cancer. AB - Carbohydrate antigens are useful markers for the serological detection of pancreatic cancer. However, data concerning the expression of structurally well defined carbohydrate antigens in normal and malignant pancreatic tissue is quite limited. The Lex and Leg antigens are closely related carbohydrate antigens synthesized on type 2 blood group oligosaccharide side chains of glycolipids and glycoproteins. Monoclonal antibodies anti-SSEA-1 and AH6 recognize "simple" Lex and Ley epitopes, respectively, regardless of the length of the carrier carbohydrate. Other monoclonal antibodies recognize Lex (FH4), sialyl Lex (FH6, IB9) or Ley (KH1, CC-1, CC-2) carried only by elongated type 2 side chains with or without internal alpha 1,3 fucosyl substitution. The present comparative immunohistochemical study used tissues of normal pancreas, chronic pancreatitis, and pancreatic cancer to determine the normal expression of Lex and Ley antigens in the pancreas and to elucidate any cancer-associated alterations. Lex-related antigens were not expressed in normal pancreas, expressed in only 10-20% of chronic pancreatitis tissues, but expressed in 50-70% of pancreatic cancer tissues. The frequency of Lex-related antigen expression in pancreatic cancer tissues was lowest in poorly differentiated cancers. Within a given specimen, at least three or all four of the Lex recognizing monoclonal antibodies were simultaneously expressed. Unlike Lex antigens, Ley-related antigens were expressed in 32-77% of specimens of normal pancreas, with similar frequencies in specimens of chronic pancreatitis and pancreatic cancer. In normal pancreas, simple Ley was expressed by both ductal and acinar cells, but extended Ley antigens were expressed only by acinar cells. In pancreatic cancer, extended Ley antigen expression was found in less than 10% of poorly differentiated tumors. Coexpression among the Ley-related antigens was less common than with the Lex related antigens. Also in cancer specimens, simple Lex and simple Lex antigens were often concordantly expressed, whereas extended Lex and extended Ley antigen expression was often discordant. Hyperplastic ducts and ductules associated with pancreatic cancer expressed Lex-related antigens more frequently than morphologically similar lesions associated with chronic pancreatitis. These results demonstrate that Lex-related antigens are cancer-associated determinants in the human pancreas. The discrepant expression between Lex and Ley antigens in these tissues implies altered regulation of fucosyltransferase activity associated with the malignant state. PMID- 3335017 TI - Effects of acute pH 6.6 and 42.0 degrees C heating on the intracellular pH of Chinese hamster ovary cells. AB - Incubation of Chinese hamster ovary cells in pH 6.6 medium for 4 h prior to and during 42.0 degrees C heating enhanced thermal cell killing compared to cells heated under normal pH 7.3 conditions. We examined the relationship between the extracellular pH and intracellular pH (pHi) of Chinese hamster ovary cells using a flow cytometer with the pH-sensitive fluorescent molecule 2,3 dicyanohydroquinone. Using either normal (7.3) or low (6.6) pH conditions, the mean pHi and population pHi heterogeneity was studied as a function of time at 42.0 degrees C. Cells incubated at pH 6.6 for 4 h had a resting pHi 0.14 to 0.19 pH units lower than cells at normal pH 7.3, indicating the presence of an active pHi regulatory system. Heating 1 h at 42.0 degrees C at normal pH caused an increase in the pHi of 0.14 pH units. With further heating the cells gradually returned to the unheated (7.3) control levels. Similar pHi changes were observed with the cells incubated and heated at pH 6.6. However, the mean pHi was always more acidic than cells heated at normal pH. Active pHi regulation was still possible for a substantial (greater than 30%) number of cells even after 10 h of heating under low pH conditions. These results suggest that a breakdown in pHi regulation is not the mechanism of low pH-induced heat sensitization. PMID- 3335016 TI - Distribution of mono-, di, and tri-O-acetylated sialic acids in normal and neoplastic colon. AB - The purpose of this study was to compare the expression of O-acetylated sialic acids on normal colonic epithelial cells to that on primary and metastatic human adenocarcinoma of the colon and rectum. In 24 cases, the relative percentages of biosynthetically labeled non-, mono-, di-, and tri-O-acetylated sialic acids were measured after hydrolytic release, separation, and identification by paper chromatography. In one case, the presence of di- and tri-O-acetylated sialic acids was confirmed by fast atom bombardment-mass spectral analysis. Differences were observed in the expression of sialic acids between normal colonic epithelium, "uninvolved" colon mucosa remote to a colonic adenocarcinoma, and colonic adenocarcinoma. The levels of mono- and tri-O-acetylated sialic acids accounted for the difference in the ratios of sialic acids expressed between normal and "uninvolved" colonic mucosa, while the total amount of O-acetylation was unchanged. However, no difference was observed in the relative amounts of non and O-acetylated sialic acids between either fresh and tissue culture established colon carcinomas, or fresh and tissue culture-established liver metastasis derived from carcinoma of the colon. The relative expression of these O-acetylated sialic acids molecules appears to vary according to tissue type. This study suggests that individuals with adenocarcinoma of the colon express a field defect resulting in abnormal ratios of O-acetylated sialic acids. PMID- 3335018 TI - Bromodeoxyuridine enhancement of 1-beta-D-arabinofuranosylcytosine metabolic activation and toxicity in HL-60 leukemic cells. AB - We tested whether bromodeoxyuridine (BrdUrd), an analogue of thymidine (dThd), enhances 1-beta-D-arabinofuranosylcytosine (ara-C) metabolic activation, as does dThd. HL-60 cells were exposed to 10, 100, or 1000 nM ara-C for 3 h. Simultaneous exposure of log phase HL-60 cells to BrdUrd (1-1000 microM) and ara-C for 3 h resulted in enhancement of ara-C incorporation into DNA, with a doubling of incorporation in response to 10 nM ara-C occurring at concentrations of BrdUrd greater than 100 microM. Preexposure of cells to BrdUrd for 16 h followed by addition of ara-C for 3 h resulted in even greater ara-C incorporation into DNA. This increase was most marked at the lower concentrations of ara-C (10 and 100 nM), where approximately 3-fold enhancement of ara-C incorporation was observed in response to BrdUrd concentrations greater than 100 microM. Intracellular pools of 1-beta-D-arabinofuranosyl-CTP increased significantly (up to 3-fold) following 16-h exposure to BrdUrd (30, 100, or 300 microM) at all concentrations of ara-C tested. The ara-C phosphorylating activity of cell-free extracts obtained following 16-h exposure of cells to BrdUrd increased 1.5- to 2.3-fold over control. Intracellular dCTP pools fell to approximately 50% of control after exposure to 750 microM BrdUrd or dThd. Exposure to BrdUrd for 16 h caused a concentration-dependent increase in cells with S-phase DNA content, as assessed by flow cytometry, with a doubling of cells in S phase (to 60%) observed in response to 500 microM BrdUrd. HL-60 cells exposed to identical conditions of BrdUrd for 3 h showed no significant alteration in cell cycle phase distribution. Thus, although BrdUrd does increase cells in S phase, the increased ara-C incorporation caused by BrdUrd cannot be explained solely on a cytokinetic basis since enhancement of incorporation was observed after a 3-h exposure of cells to BrdUrd and ara-C. The combination of ara-C (100 nM) and BrdUrd (100-1000 microM) exhibited cytotoxic synergism, as measured by the fluorescein diacetate/propidium iodide method. These data demonstrate a clear potential for BrdUrd modulation of ara-C metabolism in human leukemia. Additionally, the interaction of BrdUrd and ara-C should be considered in the interpretation of studies of the effects of ara C on DNA synthesis as measured by flow cytometric quantification of incorporated BrdUrd. PMID- 3335019 TI - Decontamination and disposal of nitrosoureas and related N-nitroso compounds. AB - An improved procedure for chemically decontaminating residues of nitrosoureas and related N-nitroso compounds ("nitrosamides") commonly used in the cancer research laboratory is proposed. Treatment of accumulated wastes with aluminum:nickel alloy powder while progressively increasing the basicity of the medium consistently led to at least 99.98% destruction of each nitrosamide tested. Hazardous diazoalkanes were never detected in yields of greater than 0.1%. The mutagenicity of the completed reaction mixtures was never more than 3 times background except when the N-nitroso compound contained a 2-chloroethyl group. In most cases, the completeness of reaction could be determined chromatographically, not only to demonstrate the disappearance of the starting N-nitroso compound, but also to follow production of identifiable products in sufficient abundance to account for the starting material destroyed; none of the organic products observed was mutagenic in any of the four tester strains used. The procedure described herein proved reliable in two checker laboratories besides our own when applied to mixtures of seven N-nitroso compounds: N-methyl-N-nitroso-p-toluene sulfonamide; N-methyl-N-nitrosourethane; N-methyl-N-nitrosourea; N-methyl-N' nitro-N-nitrosoguanidine; N-ethyl-N-nitrosourea; N-ethyl-N'-nitro-N nitrosoguanidine; and N-ethyl-N-nitrosourethane. All of the other procedures investigated for destruction of nitrosamides, including the widely used approach of dissolving the nitrosamides in alkali, were associated with important disadvantages. PMID- 3335020 TI - Lectin-binding proteins in nuclear preparations from rat liver and malignant tumors. AB - Lectin binding [concanavalin A, biotinylated ricinus communis agglutinin, and biotinylated succinylated wheat germ agglutinin (B-SWGA)] was used to detect the glycosylated proteins associated with a residual protein fraction [insoluble in 4% sodium dodecyl sulfate and termed the nuclear residual fraction (NRF)] or with nuclear matrix preparations from normal rat liver, azo dye (3'-MeDAB)-induced rat hepatoma, and Walker 256 transplantable carcinosarcoma. One- and two-dimensional gel electrophoresis were used with lectins, polyclonal antisera, and monoclonal antibody binding to characterize some of the glycoconjugates. Two polypeptide bands with approximate molecular weights of 95,000 and 55,000, shown previously to be present only in the induced tumor cells and the Walker 256 tumor, were reactive with lectins. In addition, a Mr 62,000 protein reacted only with B-SWGA in the nuclear matrix fractions from normal rat liver and the induced hepatoma. A polypeptide band (approximate molecular weight, 213,000) in the Walker 256 NRF reacted with concanavalin A and biotinylated ricinus communis agglutinin. One polypeptide band (approximate molecular weight, 182,000) reacted with concanavalin A in all three tissues, with biotinylated ricinus communis agglutinin and B-SWGA in the Walker NRF, and with B-SWGA in the hepatoma NRF. Another polypeptide band (approximate molecular weight, 138,000), reactive with all three lectins, was present in all three tissues. Our findings are consistent with previous reports of lectin binding proteins in the eukaryotic cell nucleus and indicate that certain glycoproteins isolated in nuclear preparations are found specifically in 3'-MeDAB-induced hepatoma and Walker 256 transplantable carcinosarcoma. PMID- 3335021 TI - Marker polypeptides distinguishing between cancer cell clones with high and low potential for spontaneous metastasis in murine fibrosarcoma cells. AB - Consistent differences in expression of specific proteins were observed between numerous cancer cell clones with high and low potential for spontaneous metastasis. Seventeen clones from two unrelated murine fibrosarcomas were examined concomitantly for spontaneous formation of lung metastases and for occurrence of individual polypeptide differences by high resolution two dimensional gel electrophoresis. One of the identified marker polypeptides, designated Hi:2, was very strongly expressed by all 10 strongly metastatic clones, but was absent from 6 and only weakly expressed by one of the 7 weakly metastatic clones. Another marker polypeptide, designated Lo:6, was consistently most strongly expressed by the weakly metastatic clones. Among the approximately 2000 individually separated cellular polypeptides, only these two marker polypeptides consistently distinguished between the strongly and weakly metastatic clones from both fibrosarcomas. Five other polypeptides also distinguished between highly and weakly metastatic clones, but not as stringently. PMID- 3335022 TI - Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. AB - For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening. PMID- 3335024 TI - Enhancement of chemical carcinogenesis in mice by systemic effects of ultraviolet irradiation. AB - The present study was designed to determine the systemic influence of ultraviolet (UVB) irradiation upon subsequent carcinogenesis induced by benzo(a)pyrene. The source of UV irradiation consisted of six Westinghouse FS-40 fluorescent sunlamps. Female BALB/c mice received five 30-min dorsal UVB radiation treatments per week for 13 wk. At the end of 13 wk, irradiated and unirradiated mice received ventral applications of 0.1 or 1.0 mg of benzo(a)pyrene twice weekly for 20 or 10 wk, respectively. At 18 wk after the first benzo(a)pyrene treatment, mice receiving 0-, 0.1-, or 1.0-mg benzo(a)pyrene treatments bore 0, 12, or 29 tumors per group of 18 mice, respectively. Tumor-free survival was significantly shortened in the UV-irradiated hosts as compared with unirradiated hosts, as analyzed by the Kaplan-Meier method of survival analysis. Therefore, ultraviolet irradiation induced a systemic effect which enhanced subsequent tumor induction by benzo(a)pyrene in a manner which was dependent on the dose of benzo(a)pyrene. PMID- 3335023 TI - Energy substrate utilization in freshly isolated Morris Hepatoma 7777 cells. AB - Freshly isolated Morris Hepatoma 7777 cells were prepared for a study of the utilization of palmitate and beta-hydroxybutyrate as metabolic fuels compared to other major energy substrates (glucose and glutamine). These cells were capable of oxidizing both [U-14C]palmitate and beta-[3-14C]hydroxybutyrate although the rates accounted for only 10 +/- 3 (SD) and 9 +/- 4% of total oxygen consumed, respectively; n = 4. Incorporation of [U-14C]glutamine and [U-14C]glucose carbon into 14CO2 made up for 38 +/- 13 and 9 +/- 2% of oxygen consumed by these cells, respectively. The conversion of glucose carbon into lactate was estimated to supply 26 +/- 6% of ATP. Thus, glutamine oxidation and lactate formation from glucose were the major contributors to estimated ATP needs. Conversion of these substrates into lipids was also studied and compared with oxidized products. Incorporation of glucose, glutamine, and beta-hydroxybutyrate into nonsaponifiable lipids and fatty acids was only 6.0 +/- 2.9, 0.8 +/- 0.2 and 17.7 +/- 6.65% (n = 3) of their respective rates of CO2 formation. This suggests that in freshly isolated Morris Hepatoma 7777 cells, citrate export from the mitochondria for cholesterogenesis and lipogenesis is a minor fate of substrate carbon entering the mitochondria for oxidation. PMID- 3335025 TI - Antibody-mediated killing of human tumor cells by attached effector cells. AB - Cultured human melanoma, lung carcinoma, and colon carcinoma cells were isotope labeled and incubated with a combination of effector cells and mouse monoclonal antibodies to tumor-associated cell surface antigens. The former were derived from the peritoneal cavity of mice or from peripheral blood of healthy human subjects. Monoclonal antibodies MG-21, 96.5, and L6, which are IgG3, IgG2a, and IgG2a, respectively, were all cytolytic when added in the presence of mouse effector cells to target cells expressing the relevant antigens. MG-21 and L6 were cytolytic also with human effector cells, while monoclonal antibody 96.5 was not. The effector cells attached to plastic surfaces, stained with neutral red, were peroxidase positive and mediated their effect over a 24- to 72-h time period as compared to the 4 h generally sufficient for antibody-dependent cellular cytotoxicity by natural killer cells. In tests on human effector cells with a fluorescence-activated cell sorter, they stained with antibody LCM-3C10 to the CD14 antigen, as well as with antimonocyte antibody 61D3. The cytolytic effect of human effector cells and antitumor antibody was not abolished by incubation with antibodies FC2 or 60.3 to CD16 and CD18, respectively, known to interfere with the antibody-dependent cellular cytotoxicity activity and natural killing of natural killer cells. This suggests, together with the other findings, that the effector cells were macrophages. PMID- 3335026 TI - Expression of two different endogenous galactoside-binding lectins sharing sequence homology. AB - The endogenous beta-D-galactoside-binding lectins of UV-2237-IP3 fibrosarcoma cells consist of two polypeptides with molecular weights of 14,500 (L-14.5) and 34,000 (L-34). Recently we constructed complementary DNA (cDNA) libraries from these cells in the expression vector lambda gt11 and isolated and characterized cDNA clones encoding the two lectin species (A. Raz et al., Exp. Cell Res., 173: 109, 1987). We report here on the similarity in structure and gene number in genomic DNA of the fibrosarcoma cells and syngeneic normal mouse lung DNA. The expression of mRNAs hybridizing to these cDNAs was evaluated in three pairs of normal versus their transformed cell variants. Messenger RNA corresponding to the Mr 34,000 lectin was present more abundantly in the transformed cells than in their normal counterparts, while no difference was detected between the cell pairs with respect to mRNA levels corresponding to the Mr 14,500 lectin. We have established the nucleotide sequences of the two cDNA clones. The deduced amino acid sequence of L-14.5 lectin cDNA clone (L-3) is significantly homologous to the sequence of six other L-14 vertebrate galactoside binding lectins. The sequence of the Mr 34,000 lectin cDNA clone (M5) revealed that it shares a stretch of 39 amino acids with all of the L-14 galactoside binding lectins, irrespective of origin of the species, suggesting both that they are all derived from a common ancestral gene, and that this domain is necessary for similar sugar binding properties. PMID- 3335027 TI - Synergistic cytotoxic and antitumor effects of recombinant human tumor necrosis factor and hyperthermia. AB - A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and hyperthermia was demonstrated both in vitro and in vivo. The cytotoxicity of rH-TNF against L-M cells in incubation for 12 h at 38.5 and 40 degrees C based on the concentration necessary for 50% cytotoxicity was, respectively, 125 and more than 500 times as high as in similar incubation at 37 degrees C. As observed 18 days after implantation of Meth-A fibrosarcoma cells in mice, single i.v. administration of rH-TNF at 1000 units/mouse resulted in complete cures in five mice when performed in combination with hyperthermia (40 degrees C), whereas rH-TNF alone in the same dose resulted in 27.1% inhibition of tumor growth and hyperthermia alone had no appreciable effect on tumor growth. The i.v. administration of rH-TNF three times at 100 or 300 units/mouse together with hyperthermia (40 degrees C) resulted in 41.2 and 89.0% tumor growth inhibition, respectively; similar administration without hyperthermia appeared to have little or no appreciable effect on tumor growth. The results suggest that combination therapy including rH-TNF and hyperthermia may be of value in the treatment of malignancy in human patients. PMID- 3335029 TI - Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. AB - Spontaneous wheat germ agglutinin (WGA)-resistant mutants of the MeWo human malignant melanoma line were isolated after sequential selection in increasingly toxic concentrations of WGA, without prior mutagenesis. They were isolated in an attempt to obtain "membrane glycosylation mutants" having significantly altered metastatic properties when grown in nude mice, and to characterize the biochemical (oligosaccharide) changes associated with altered metastatic behavior. The lines were assessed for their sensitivity to other lectins, membrane glycoprotein profiles, ploidy levels, and their ability to produce "artificial" metastases in nude mice after i.v. inoculation. One mutant, called 70-W, manifested a 3- to 4-fold resistance to WGA compared with wild-type cells. When inoculated into NIH Swiss nude mice, 70-W cells not only produced extensive lung colony formation but also showed an extraordinary ability to disseminate widely and extensively in a clinical fashion to many extrapulmonary sites such as the subcutis, mesentery, muscle, and brain. Moreover the majority of these metastases were deeply pigmented facilitating visual identification of very small visceral metastases. A second mutant called 3S5 was isolated and found to be highly resistant to WGA (greater than 20-fold resistance). This line was virtually devoid of metastatic ability and was found by biochemical analysis to be phenotypically similar to the class I WGA resistant non-metastatic mutants previously isolated from the highly metastatic murine tumor MDAY-D2 which are known to be deficient in sialic acid and galactose. The similarity between these and earlier results using lectin resistant mutant rodent cell lines strongly suggests that sialylated glycoconjugates contribute to the metastasis of both animal and human tumors of different tissue origin. These new spontaneously derived WGA resistant MeWo mutants should be valuable new tools for the study of human tumor progression in vivo and factors involved in metastasis, especially the contribution of oligosaccharide moieties of cell surface glycoconjugates. PMID- 3335028 TI - Phorbol ester induction of 8-lipoxygenase in inbred SENCAR (SSIN) but not C57BL/6J mice correlated with hyperplasia, edema, and oxidant generation but not ornithine decarboxylase induction. AB - Several responses suggested to be critical components of phorbol ester tumor promotion were compared in 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion sensitive SSIN and TPA promotion-resistant C57BL/6J mice. SSIN mice treated topically with 2 micrograms of TPA showed extensive hyperplasia accompanied by edema, measured as a 26% increase in water content of the skin. Only a very slight hyperplasia and 7% increased water content occurred after TPA treatment of C57BL/6J mice. The induction of ornithine decarboxylase was determined to be the same both in vivo and in vitro for SSIN and C57BL/6J mice, which does not correlate with the histological observations. Because hyperplasia and inflammation can be mediated by arachidonic acid metabolites, it was hypothesized that differences in this metabolic pathway would correlate with the histological responses. No significant qualitative or quantitative differences, however, were observed in the profiles of the major cyclooxygenase products between the strains of mice. Prostaglandin E2, the principal prostaglandin, was synthesized at a 3 fold greater level than prostaglandins D2 or F2 alpha in response to TPA. The most abundant lipoxygenase product was 12-hydroxyeicosatetraenoic acid followed by 8-, 15-, and 5-hydroxyeicosatetraenoic acid. 8-Lipoxygenase activity is elevated 24 h after TPA treatment in the SSIN mice by approximately 4-fold; no elevation is seen in C57BL/6J mice. A comparison of the oxidant response to TPA as well as to phospholipase C showed that SSIN epidermal cells generated a higher level, measured by chemiluminescence, than C57BL/6J cells. This suggests that oxidant generation or possibly 8-lipoxygenase activity may be the basis for the sensitivity or resistance to TPA as a hyperplasiogen and as a tumor promoter. PMID- 3335030 TI - In vivo 31P nuclear magnetic resonance spectroscopy of subcutaneous 9L gliosarcoma: effects of tumor growth and treatment with 1,3-bis(2-chloroethyl)-1 nitrosourea on tumor bioenergetics and histology. AB - In vivo 31P nuclear magnetic resonance spectroscopy was used to examine the bioenergetics of the rat 9L gliosarcoma during untreated growth and in response to chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. Tumor growth was associated with a decline in the phosphocreatine and nucleoside triphosphate resonances, consistent with an increase in tumor hypoxia during untreated growth. Following chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (10 mg/kg), tumor levels of phosphocreatine and nucleoside triphosphate rebounded while the level of inorganic phosphate in the tumor declined. Histological comparison of treated and untreated tumor sections 4 days posttreatment showed that the treated tumor had a lower proportion of necrotic cells, a higher proportion of viable cells, and a 5-fold higher level of interstitial space than the control tumor. PMID- 3335031 TI - Pharmacokinetics of tumor cell exposure to [14C]methotrexate after intracarotid administration without and with hyperosmotic opening of the blood-brain and blood tumor barriers in rat brain tumors: a quantitative autoradiographic study. AB - Using quantitative autoradiography, we investigated the entry over 90 min of [14C]methotrexate (MTX) into C6 gliomas implanted bilaterally into Wistar rat brains. The [14C]MTX was administered into the right carotid artery, yielding ipsilateral "arterial" brain and tumor concentrations and contralateral "systemic" concentrations. In a separate group of tumor-bearing rats, mannitol 1.6 M was given into the right carotid artery prior to administering the [14C]MTX to disrupt the blood-brain barrier on the ipsilateral side. [14C]MTX tissue concentrations were measured in regions of 50 x 50 x 20 microns in tumor, peritumoral brain tissue (brain adjacent to tumor), and cerebral cortex. In the nonmannitol experiments, tissue concentrations from the rats at each time interval were fitted using a nonlinear curve fitting program, and the pharmacokinetic values of influx and efflux of [14C]MTX into the three compartments were calculated. The influx rate constant K1 for [14C]MTX ranged from 1.3 to 8.2 microliters/g/min in the tumor. Influx rate constants in the cortex were 1.3-1.9 microliters/g/min and in the brain adjacent to tumor were 1.7 2.8 microliters/g/min. The efflux rate constant k2 was approximated for each tissue but was less reliable than the K1 values. The k2 for tumor, brain adjacent to tumor, and cortex was always higher than the corresponding K1. Peak [14C]MTX concentrations in the tumor were highest after arterial infusion with hyperosmolar barrier disruption, lower after arterial administration without barrier modification, and lowest after systemic administration. However, cortical [14C]MTX concentration was also highest after arterial administration with barrier modification and higher than the highest tumor concentration. Furthermore, tissue exposure (concentration x time) was also highest in the cortex after barrier disruption. The [14C]MTX concentration x time (micrograms/min/g x 90 min +/- SEM) ratio between tumor and cortex after systemic administration was 33.4 +/- 4.1:15.7 +/- 1.9; after arterial administration it was 96.3 +/- 11.7:30.3 +/- 3.1; after arterial administration with barrier disruption it was 266.6 +/- 28.8:311.2 +/- 15.9. The greatest tumor:cortex ratio (3.1:1) occurred with arterial drug administration without barrier disruption. Disrupting the barrier enough to permit increased tumor exposure actually increased cortical exposure to a greater degree. The resulting poorer therapeutic ratio would not appear to support this technique in humans, at least for neurotoxic drugs. PMID- 3335032 TI - Cytogenetic changes in rat tracheal epithelial cells during early stages of carcinogen-induced neoplastic progression. AB - The cytogenetic changes in enhanced growth (EG) variants of rat tracheal epithelial cells in culture were examined. These variants which are detectable at 35 days after carcinogen exposure are the first phenotypic alteration in the multistep neoplastic process studied in this model system. Karyotypic analysis of N-methyl-N'-nitro-N-nitrosoguanidine-induced EG variants at Day 35 was made possible by the development of an in situ method of cytogenetic analysis on intact colonies containing too few cells for conventional chromosome preparation methods. Of the transformed EG variant colonies in both control and N-methyl-N' nitro-N-nitrosoguanidine-treated groups, 62-78% had abnormal karyotypes which included numerical and structural changes. There were no specific chromosome changes, although aberrations of chromosomes 3 and 4 were recurrently observed. However, some colonies of even the most morphologically transformed EG variants were composed of only diploid cells. To confirm this finding 10 EG variant colonies were bisected and half of the clone was prepared for chromosome analysis and the other half was subcultured to measure the clonogenicity and karyotypes of the cells. Cells from 3 colonies plated very poorly on 3T3 feeders and therefore no karyotypic analysis of the colony-forming cells was possible; the cells of the 3 parental colonies were diploid. Three other parental colonies were predominantly diploid (80-90%) but upon replating the resultant daughter colonies had progressively smaller fractions of diploid cells indicating a selection for cells with abnormal karyotypes. When more selective conditions were used (i.e., growth after removal of the feeder cells), the percentage of abnormal cells increased even further. In one case the parental cells had a karyotypic alteration in the long arm of chromosome 4 and this karyotypic alteration was accentuated in the daughter colonies. Thus, selection of cells with increased growth ability upon subculturing or growth in the absence of feeder cells (properties associated with the acquisition of immortality) resulted in concomitant selection for cells with abnormal karyotypes. Since some of the carcinogen-induced rat tracheal epithelial cells expressing the EG variant phenotype were diploid, it is possible that the first step in this transformation process is an epigenetic change. However, most of the diploid cells became terminal. The aneuploid subpopulations present in these colonies have a selective growth advantage and comprise the cell compartment that expresses continued growth, immortality, and ultimately tumorigenicity. PMID- 3335033 TI - Mechanisms of induction of ornithine decarboxylase activity in tracheal epithelial cells by asbestiform minerals. AB - Asbestos induces a constellation of biological responses in cells of the respiratory tract that are similar to those of classical tumor promoters. In this regard, induction of ornithine decarboxylase (ODC) activity and increased incorporation of [3H]thymidine have been documented after addition of crocidolite and chrysotile asbestos to a hamster tracheal epithelial cell line (J. M. Landesman and B. T. Mossman, Cancer Res., 42:3669-3675, 1982). The objectives of studies here were to determine: (a) the importance of geometry, size, and/or chemical composition of asbestos fibers on induction of ODC activity; and (b) the possible involvement of calcium and/or protein kinase C in asbestos-induced ODC activity. After addition for 24 h to confluent hamster tracheal epithelial cells, fibers of crocidolite, chrysotile, and glass in medium containing fresh serum caused a significant increase in ODC activity. Stimulation of ODC was not observed when nonfibrous analogues (riebeckite, antigorite, and glass particles) were used. Sized preparations of long (greater than 10-micron length) chrysotile fibers were more potent in enhancing ODC activity than shorter (less than or equal to 2-micron length) fibers at similar concentrations. The mechanisms of ODC induction by asbestos were probed by adding the calcium channel blockers (verapamil and nifedipine) and inhibitors [10(-5) to 10(-7)M of 1-(5 isoquinolinylsulfonyl)-2-methylpiperazine, of N-[2-(methylamino)ethyl]-5 isoquinolinesulfonamide, of TMB-8, and of palmitoyl carnitine] of protein kinase C simultaneously with chrysotile asbestos. These agents inhibited ODC activity by chrysotile in a dosage-dependent fashion. Results suggest that the fibrous geometry and length of asbestos fibers are critical in initiating ODC activity in airway epithelial cells. Moreover, they implicate the importance of calcium and protein kinase C in asbestos-induced mitogenic responses. PMID- 3335035 TI - Cancer in migrants to Australia: extending the descriptive epidemiological data. AB - Australia experienced a large influx of European migrants during the period 1950 1975. The descriptive epidemiological data on cancer rates within the major migrant groups, reviewed here, provide strong evidence of environmental and behavioral influences on the etiology of various cancers. The opportunity to extend the conventional type of data analysis, to include an examination of the effect of duration of residence upon cancer risk, provides further insight into cancer etiology. The possibilities of further exploring the descriptive data are also discussed, and both the desirability and the timeliness of mounting analytical studies of the Southern European migrants to Australia are emphasized. PMID- 3335034 TI - Progressive growth of fish tumors after transplantation into thymus-aplastic (nu/nu) mice. AB - The nude mouse does not reject xenografts of malignant and nonmalignant tissues of mammalian or avian origin, due to a deficiency of functional T-lymphocytes. In this study, tissue from a cold-blooded vertebrate, a teleost fish, was for the first time successfully transplanted to Swiss albino nu/nu mice. Malignant melanotic melanoma of Xiphophorus transplanted to nude mice showed progressive growth and could be serially passaged. In vitro culture experiments revealed that the fish tumor cells adapt to the physiological conditions of the mammalian host, most obviously to the body temperature. On the other hand, fish-specific morphological characters and biochemical features, e.g., expression of a melanoma associated antigen, were retained. This experiment demonstrates the enormous capacity of the melanoma cells to adapt to severe changes in their environment, which even enables them to overcome the physiological barriers between such taxonomically distant vertebrate groups as fish and mammals. PMID- 3335036 TI - Bryostatin 1 antagonizes the terminal differentiating action of 12-O tetradecanoylphorbol-13-acetate in a human colon cancer cell. AB - 12-O-Tetradecanoylphorbol-13-acetate (TPA), a highly active representative of the tumor-promoting phorbol esters, induces a rapid terminal differentiation of a human colon cancer cell line. Bryostatin 1, a macrocyclic lactone, completely counteracts this effect of TPA and promotes continued replication. The observed responses provide a system for identifying cellular processes which are involved in the induced terminal differentiation of human colon cancer cells. PMID- 3335038 TI - Inhibition of gap junctional blockage by palmitoyl carnitine and TMB-8 in a rat liver epithelial cell line. AB - Exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to inhibit gap junctional intercellular communication (GJIC) in many cell types in vitro. Using a scrape loading/dye transfer technique, TPA was shown to cause a dose dependent and transient inhibition of GJIC in WB-F344, a normal rat liver epithelial cell line. Such a down-modulation of intercellular communication was found to be associated with an increase in protein kinase C (PKC) activity. Translocation of this activity to the particulate fraction occurred 10 min after exposure to 16 nM TPA and was consistent with the time course needed to inhibit GJIC. After 6 h exposure to TPA, essentially all the PKC activity was lost concurrent with the recovery of communication in these cells. During this time, the cells also became refractory to inhibition by further addition of TPA. Blockage of communication induced by TPA in WB cells was prevented by treating the cells with 23 microM palmitoyl carnitine for 1 h or 100 microM 8-N, N (diethylamino)-octyl-3,4, 5-trimethoxybenzoate for 30 min. The results indicate that TPA transiently modulates GJIC in WB cells and PKC activation is possibly involved in blockage of communication in these cells. PMID- 3335037 TI - Effects of organosulfur compounds from garlic and onions on benzo[a]pyrene induced neoplasia and glutathione S-transferase activity in the mouse. AB - In the present study, eight organosulfur compounds from garlic and onions were studied for their inhibitory effects on benzo[a]pyrene (BP)-induced neoplasia of forestomach and lung of female A/J mice when administered 96 and 48 h prior to carcinogen challenge. These compounds had one, two or three linearly connected sulfur atoms. They included the four allyl group-containing derivatives: allyl methyl trisulfide (AMT), allyl methyl disulfide (AMD), diallyl trisulfide (DAT), and diallyl sulfide (DAS), and also four corresponding saturated compounds in which propyl groups were substituted for the allyl groups. All four allylic compounds inhibited BP-induced neoplasia of the forestomach. The saturated analogs were almost without inhibitory activity, indicating the importance of the allyl groups. DAT, which contains two allyl groups, was more potent than AMT, which contains only one allyl group, thus providing further evidence for the role of allyl groups in the inhibitory effects observed. DAS and AMD, but not DAT or AMT, inhibited pulmonary adenoma formation. The fact that in the lung the monosulfide and disulfide inhibited, but the trisulfide did not inhibit, indicates that the number of sulfur atoms in the molecule can control the organ sites at which protection against carcinogenesis will occur. All four allylic compounds induced increased glutathione S-transferase (GST) activity in the forestomach, but varied in their capacity to induce GST in lung, liver and small bowel. Their saturated analogs produced little or no induction. In evaluating relationships between diet and cancer, it would be useful to consider the possible role of garlic and onion organosulfur compounds as protective agents. In addition, further studies of this class of chemicals might lead to the identification and development of useful new chemopreventive compounds. PMID- 3335039 TI - Metabolic activation of 7-ethyl- and 7-methylbenz[a]anthracene in mouse skin. AB - The carcinogen 7-methylbenz[a]anthracene (7-MBA) is considered to be metabolically activated via its bay-region dihydrodiol-epoxide, trans-3,4-dihydro 3,4-dihydroxy-7-methyl-benz[a]anthracene 1,2-oxide (7-MBA-3,4-diol 1,2-oxide). When tested on mouse skin, a target tissue for polycylic aromatic hydrocarbon carcinogenesis, 7-ethylbenz[a]anthracene (7-EBA) was much less active than 7-MBA, and this difference may be due to differences in the pathways by which the two compounds are metabolized and activated. In the present work, the metabolism by mouse-skin microsomes of both hydrocarbons to dihydrodiols has been examined. Both were metabolized to a similar extent with the 8,9-dihydrodiols being detected as the predominant metabolites. The 3,4-, 5,6-and 10,11-dihydrodiols of 7-MBA and the 3,4- and 10, 11-dihydrodiols of 7-EBA, were also detected. 7-MBA was found to bind covalently to microsomal protein at 10 times the level of 7 EBA. The covalent binding of benz[a]anthracene (BA), 7-EBA and 7-MBA to DNA in mouse skin following topical application was determined using the 32P postlabelling assay. The results correlated with the relative carcinogenic activities of the compounds with 7-MBA binding at five and nine times the level of 7-EBA and BA respectively. For all three hydrocarbons, the major hydrocarbon: 32P-labelled nucleoside bisphosphate, eluted in the same area of the TLC maps, suggesting the involvement of a common type of bay-region dihydrodiol-epoxide intermediate. PMID- 3335040 TI - Monoclonal antibodies for the immunoassay of mutagenic compounds produced by cooking beef. AB - A family of 2-amino-N-methylimidazoazaarene (AIA) mutagens are produced in meats by cooking, and are of concern as potential carcinogens in the human diet. These are potent genotoxins in bacterial mutation assays, but are present only in trace quantities in cooked foods. Conventional analytical chemistry methods have allowed us to identify six members of the AIA class, but these methods are much too labor-intensive for us to quantify mutagens in large numbers of meat samples. To improve the assay of these mutagens we have developed six monoclonal antibodies (named IQ-1, IQ-2, AIA-1, AIA-2, AIA-4, and AIA-7) and demonstrated their utility in an immunoassay for cooked food mutagens. Each antibody has its own unique binding selectivity pattern; some are compound-specific, and some class-specific. A comparison was made between cooked beef extracts that differed 200-fold in mutagenic activity. The high-mutagen extract had significantly more material that was immunologically cross-reactive with the anti-AIA antibodies than did the low-mutagen extract. Taken as a set, these antibodies will allow rapid quantitation of foods for several AIA mutagens, and will aid in the isolation and characterization of other AIAs and AIA-metabolites. PMID- 3335042 TI - Anticarcinogenic activity of quinacrine in the rat mammary gland. AB - Mammary carcinogenesis studies were conducted to determine the chemopreventive activity of quinacrine, an antimalarial drug which suppresses the production of arachidonic acid from phospholipid through inhibition of phospholipase A2. Beginning 1 week after a single i.v. dose of N-methyl-N-nitrosourea (MNU), female Sprague-Dawley rats were fed a semi-purified diet supplemented with 0 or 75 mg quinacrine/kg diet. Quinacrine reduced cancer incidence and carcinoma multiplicity in rats administered 20 mg MNU/kg body wt, but had no inhibitory activity in rats treated with 50 mg MNU/kg. These data suggest that pathways of arachidonic acid metabolism in addition to cyclooxygenase present useful targets for mammary cancer chemoprevention. However, the chemopreventive activity of quinacrine may be limited by toxicity. PMID- 3335041 TI - Evidence for 4-(3-pyridyl)-4-oxobutylation of DNA in F344 rats treated with the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine. AB - DNA was isolated from tissues of F344 rats 24 h after treatment by s.c. injection with [5-3H]4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ([5-3H]NNK) or [5-3H]N' nitrosonornicotine ([5-3H]NNN). It was hydrolyzed with acid or at pH 7, 100 degrees C, and the hydrolysates were analyzed by HPLC. The major product in each case was identified as 4-hydroxy-1-(3-pyridyl)-1-butanone, formed by hydrolysis of a DNA adduct. It was detected in DNA from the livers of rats treated with [5 3H]NNK or [5-3H]NNN, and in DNA from lungs of rats treated with [5-3H]NNK. These results demonstrate that 4-(3-pyridyl)-4-oxobutylation of DNA occurs in rats treated with NNK or NNN, and are consistent with the hypothesis that these nitrosamines are metabolically activated by alpha-hydroxylation. PMID- 3335043 TI - Mono-, di- and trimethylamine in human gastric fluid: potential substrates for nitrosodimethylamine formation. AB - Nitrosodimethylamine (NDMA) is a potent carcinogen in a wide variety of animal species. In experimental animals, dimethylamine and nitrite, precursors of NDMA, are found in gastric fluid where the acidic conditions are suitable for formation of nitrosamines. In this study we measured the concentrations of mono-, di- and trimethylamine (MMA, DMA and TMA) in gastric fluid from humans, rats, dogs and ferrets, as well as in saliva, blood and urine from humans. Human gastric fluid contained 3.7 +/- 0.4 (SEM) nmol/ml MMA, 12.6 +/- 1.4 nmol/ml DMA and 2.0 +/- 0.4 nmol/ml TMA. MMA, DMA and TMA concentrations in human gastric fluid were similar to those present in human saliva and blood, but were much lower than those present in human urine. The concentrations of these amines in human gastric fluid were lower than those measured in gastric fluid from experimental animals. When we added sodium nitrite to human gastric fluid, NDMA was formed. We have shown that DMA is normally present in human gastric fluid, and that it can be nitrosated to form NDMA. PMID- 3335044 TI - Rat liver immuno-ultrastructural localization of the specific (4-5S) 3 methylcholanthrene-binding protein; evidence for its involvement as a receptor protein in cytochrome P-4501A1 induction. AB - Two major specific carcinogen-binding proteins are thought to be involved in the regulation of hepatic cytochrome P-4501A1 induction in response to polycyclic aromatic hydrocarbons. We have raised both mono- and polyclonal antibodies which specifically interact with one of these proteins, the 4-5S-specific binding protein. Antibody binding was found to both the specific (4-5S) 3 methylcholanthrene (3MC) binding activity present in rat hepatic cytosol (as quantified on sucrose gradients or by Sephacryl S-300 gel filtration chromatography) and to the purified 39,000-dalton protein previously reported as the specific 3MC-binding protein (determined by Western blot analyses). No immunoreactivity was observed to cytosolic proteins in the region of 70,000 or 95,000 daltons (i.e. corresponding to the Ah receptor). We have used Western blot analyses and immunostaining of cryostat sections to demonstrate that the 4-5S specific binding protein is present predominantly in the cytoplasm but also (at lower concentration) in the nuclei of untreated Wistar rat hepatocytes. Electron micrographs of immunostained sections indicate that, following exposure to 3MC, the concentration of specific binding proteins in the nucleus increases and this is assumed to be due to translocation of specific binding protein-3MC complexes from the cytoplasm. PMID- 3335045 TI - Various short-term assays and two long-term studies with the plasticizer di(2 ethylhexyl)phthalate in the Syrian golden hamster. AB - The plasticizer di(2-ethylhexyl)phthalate (DEHP) and its main metabolite monethylhexylphthalate (MEHP) were investigated in several short-term in vitro assays, including mutagenicity in Salmonella typhimurium TA102, a strain sensitive to mutations arising as a cause of oxidative DNA damage. Also DNA amplification in SV40-transformed Chinese hamster cells and DNA damage in rat and hamster hepatocytes were investigated. The two compounds were not genotoxic in any of the test systems. Furthermore, DEHP was investigated in two long-term bioassays with Syrian golden hamsters using both i.p. (max. total dose 54 g/kg) and inhalative (7-10 mg/kg) application. In both experiments an additional group of animals received a combination treatment of DEHP with N-nitrosodimethylamine (NDMA). These studies were included in order to elucidate whether the observed influence of DEHP on the microsomal enzyme activity (Seth, 1982) may effect the carcinogenic activity of NDMA. There was no significant increase in tumor incidence after application of only DEHP via both routes. However, the occurrence of liver malignancies was significantly (P less than 0.001) reduced after the combination treatment in the inhalation study. PMID- 3335046 TI - Increased O6-alkylguanine alkyltransferase activity in Chinese hamster V79 cells following selection with chloroethylating agents. AB - Chinese hamster V79 lung fibroblasts express low levels (specific activity 2-4 fmol/mg protein) of O6-alkylguanine (O6-AG) alkyltransferase (ATase). In cells surviving selection with low doses (10 micrograms/ml) of the chloroethylating agent, mitozolomide (Mz), ATase activity was increased 5- to 8-fold. Repeated selection of such cells produced a maximal specific activity of 36-40 fmol/mg protein, whilst selection at 20 or 40 micrograms/ml result in specific activities of approximately 50 and 70 fmol/mg respectively. Only slight decreases in ATase activity were seen by 51 days after an initial selection with 10 micrograms/ml Mz. A similar effect was observed using chlorozotocin. Selected cells had a higher D37 for Mz (2.5-6.0 micrograms/ml) in comparison with control cell (D37, 0.8 micrograms/ml) but the D37s for nitrogen mustard and vincristine were closely similar in selected and control cells. Possible explanations for the increase in ATase activity are discussed. PMID- 3335047 TI - Ram seminal vesicle microsome-catalyzed activation of benzidine and related compounds: dissociation of mutagenesis from peroxidase-catalyzed formation of DNA reactive material. AB - Ram seminal vesicle (RSV) microsomal preparations activate benzidine and other arylamines to mutagenic species in a modified Ames assay. We have examined the mechanism of this activation process in more detail. The mutagenic effect was neither arachidonic acid-dependent nor indomethacin inhibitable. The mutagenic species was stable for at least 30 min in experiments in which addition of bacteria was delayed. Acetylbenzidine was a much more potent mutagen than benzidine in this system. Substitution of the acetylase-deficient tester strain TA98/1,8-DNP6 for strain TA98 markedly reduced the mutagenicity of acetylbenzidine and completely eliminated the mutagenicity of benzidine. Benzidine analogues 3,3'-dimethoxybenzidine (o-dianisidine), o-tolidine and 3,3', 5,5'-tetramethylbenzidine were not mutagenic in the RSV activation system. RSV dependent activation of all radiolabeled congeners examined resulted in covalent binding to calfthymus DNA. The rank order of binding was: 3,3'-dichlorobenzidine greater than benzidine greater than o-dianisidine greater than acetylbenzidine greater than tetramethylbenzidine. This binding required active enzyme and arachidonic acid or hydrogen peroxide. The reactive species was short-lived: delayed addition of DNA reduced the level of binding nearly to zero. Binding was inhibitable by indomethacin, but this inhibition was incomplete in the cases of dichlorobenzidine and acetylbenizidine. We conclude that the extracellular generation of peroxidase-catalyzed oxidation products does not explain the RSV microsome-dependent mutagenicity observed with these compounds. PMID- 3335048 TI - Ploidy distribution in experimental liver carcinogenesis in mice. AB - There have been several reports on the distribution of DNA in premalignant and malignant liver cells after carcinogen treatment in rodents. The most striking result so far is that ploidy distributions seems to depend more on experimental protocols and less on carcinogenesis per se. The present study demonstrates that an evaluation by means of flow cytometry and stereological image analysis yields results showing similar ploidy distributions throughout the known sequence of tissue changes seen during liver cancer development. Furthermore, our results demonstrate inter-individual differences between the lesions in each of the steps in these tissue changes, (foci, nodules and hepatocarcinomas). The present study gives no reason to conclude that changes in ploidy distribution are essential in liver carcinogenesis. PMID- 3335049 TI - Role of formaldehyde hydrazone and catalase in hydrazine-induced methylation of DNA guanine. AB - Hydrazine is acutely neurotoxic, hepatotoxic and nephrotoxic; it is also carcinogenic to liver and lung in rodents. Administration of hydrazine results in formation of 7-methylguanine and O6-methylguanine in target organ DNA of rats, mice, hamsters and guinea-pigs. It has been suggested that hydrazine reacts with endogenous formaldehyde to form a condensation product which could be metabolized to a methylating agent. Solutions of 0.50 mM hydrazine and formaldehyde have, upon mixing, NMR spectra (300 MHz) consistent with the formation of formaldehyde hydrazone but not other possible condensation products such as tetraformyltriazine or formaldehyde azine. These same solutions evidencing hydrazone formation, when incubated in an in vitro system containing post mitochondrial (S9), microsomal, cytosolic or mitochondrial cell fractions, resulted in the methylation of DNA guanine; S9 was the most active fraction. Neither the P-450 monooxygenase nor flavin monooxygenase systems appeared to be important in hydrazine/formaldehyde-induced methylation of DNA. However, sodium azide, cyanamide and carbon monoxide all inhibited S9-supported DNA methylation. Bovine liver catalase, a heme-containing cytochrome, readily transformed hydrazine/formaldehyde to a methylating agent. The data support formation of formaldehyde hydrazone as the condensation product of hydrazine and formaldehyde which is rapidly transformed in various liver cell fractions, perhaps by catalase and/or catalase-like enzymes, to a methylating agent. PMID- 3335050 TI - Carcinogenicity in rats of a mutagenic compound, 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline. AB - Carcinogenicity of 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx), which is a potent mutagen first isolated from fried beef and widely present in various cooked foods, was tested in both sexes of F344 rats. Rats were continuously given a diet containing 0.04% MeIQx or basal diet and the experiment was finished on day 429. In experimental animals, the incidence of liver, Zymbal gland, clitoral gland and skin tumors was significantly higher than in control animals. The incidence of liver tumors was 100% in males and 53% in females; most liver tumors of males were hepatocellular carcinomas and all liver tumors of females were neoplastic nodules. The incidence of Zymbal gland tumors was 75% in males and 53% in females. Clitoral gland tumors were induced in 63% and skin tumors were observed in 35% of males and 5% of females. Most of these three types of tumors were diagnosed as squamous cell carcinoma. In the control rats, liver, Zymbal gland, clitoral gland and skin tumors were not observed in either sex. PMID- 3335052 TI - Platelet activating factor: a potent constrictor of cerebral arterioles in newborn pigs. AB - This study characterized the nature of the response to platelet activating factor (PAF) in the cerebral microcirculation of the newborn pig. Pial arterioles were observed directly using a closed cranial window in chloralose-anesthetized piglets. Topical application of 10-100 ng/ml PAF produced dose-dependent decreases in pial arteriolar diameter; diameters were 193 +/- 27 microns for control, 167 +/- 25 microns at 10 ng/ml, and 129 +/- 21 microns at 100 ng/ml. Topical application of 30-300 ng/ml norepinephrine and 3-30 ng/ml U46619, a purported thromboxane A2 receptor agonist, also produced dose-dependent decreases in pial arteriolar diameter. After topical administration of U66985 (1 microgram/ml), a putative PAF antagonist, responses to PAF were attenuated significantly, but responses to norepinephrine and U46619 were unchanged. Moreover, intravenously administered U66985 (0.1 mg/kg) antagonized PAF responses as well. Responses to PAF were unchanged after cyclooxygenase and leukotriene receptor inhibition. Further, PAF did not increase cortical subarachnoid cerebrospinal fluid prostaglandin or leukotriene levels. These data indicate that PAF is a potent constrictor of cerebral arterioles in newborn pigs and that its mechanism of action is independent of formation of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. These data also suggest that U66985 may be a selective PAF antagonist that crosses the blood-brain barrier. Since PAF is an endogenous lipid released from a variety of tissues and may be an important mediator of inflammation and allergic reaction, PAF could be involved in the pathophysiology of the cerebral circulation in the perinatal period. PMID- 3335051 TI - Growth support and toxicity of homocysteine and its effects on methionine metabolism in non-transformed and chemically transformed C3H/10T1/2 cells. AB - The effects of homocysteine (Hcy) on one non-transformed (Cl 8) and two malignant clones (Cl 16 and Cl T422) of the C3H/10T1/2 mouse embryo fibroblasts, were examined with regard to toxicity, ability to support growth and effects on methionine (Met) metabolism and glutathione level. Homocysteine in its reduced form (Hcy-SH) was toxic to all cell lines, and the LD90 was estimated to be 1.0 X 10(-4) M for Cl 8 and Cl 16 cells measured by plating efficiency, 0.8 X 10(-4) M for Cl 8 and 0.3 X 10(-4) M for Cl 16 when measured by total cell growth. At toxic concentrations, Hcy-SH showed a drastic effect on cell morphology both in the presence and absence of Met. The same effect was demonstrated with L cysteine. No toxic effect was seen with homocystine (Hcy-SS-Hcy) or homocysteine thiolactone (Hcy-tl) at similar concentrations. Hcy-tl supported growth of both the non-transformed and malignant cells in Met-deficient medium but with decreasing efficiency in the order Cl 8, Cl 16 and Cl T422. The growth rate constant compared to that of Met-supplemented medium was 0.62 for Cl 8, 0.44 for Cl 16 and 0.38 for Cl T422 cells. The intracellular level of S adenosylhomocysteine (AdoHcy) increased in all three cell lines in Hcy-tl supplemented medium. The S-adenosylmethionine (AdoMet) content increased in Cl 8 cells, was constant in Cl 16 cells and decreased in Cl T422 cells under the same conditions. This resulted in a constant ratio of AdoMet/AdoHcy in the non transformed cells (Cl 8) whereas this ratio decreased by 40% in Cl 16 and by 72% in Cl T422 cells when Hcy-tl replaced Met in the medium. The ability of Hcy-tl to support growth thus seemed to correlate well with alteration in Met metabolism in this cell culture system. The intracellular level of glutathione (GSH) was measured during exponential growth, but showed small variations between non transformed cells and Cl 16 cells. However, Cl T422 cells showed a distinct lower level of GSH in Met-supplemented medium, and this increased 3- to 4-fold when Met was replaced with Hcy-tl. PMID- 3335053 TI - Effects of calcium channel blocker on responses of blood flow, function, arrhythmias, and extent of infarction following reperfusion in conscious baboons. AB - Two groups of chronically instrumented, conscious baboons were studied. The effects of coronary artery occlusion for 3 hours and reperfusion for 1 week were examined on measurements of left ventricular function, ischemic-zone wall thickness, regional myocardial blood flow, arrhythmias, and extent of necrosis. The experimental group of animals (n = 7) was treated with the calcium channel blocker nisoldipine (0.1 microgram/kg/min) from 1 hour after coronary occlusion to 3 hours after coronary reperfusion. The control group (n = 6) received the vehicle (n = 4) or saline (n = 2). The effects of coronary artery occlusion and reperfusion on arterial pressure, left ventricular systolic pressure, heart rate, and left ventricular dP/dt were similar in both groups. Systolic wall thickening was reversed to paradoxical wall thinning during occlusion in both groups, and there was no recovery to systolic wall thickening over the 1-week period in either group. There were differences in regional blood flow; during coronary artery occlusion, nisoldipine increased blood flow significantly in the endocardium and epicardium of nonischemic and ischemic zones. There was a major difference in the number of arrhythmic beats per minute on reperfusion; during reperfusion, the number of arrhythmias rose markedly in the vehicle-treated group but actually fell in the nisoldipine-treated group. The size of areas at risk, infarcts, infarcts related to the area at risk, and amount of total creatine kinase (CK) and MB-CK appearing in blood were not significantly different in the two groups. Thus, in the conscious baboon, nisoldipine administered 1 hour after coronary artery occlusion exerted a marked effect in diminishing reperfusion induced arrhythmias and improved blood flow to the ischemic zone during occlusion but did not salvage ischemic tissue. PMID- 3335054 TI - Abnormalities of dynamic ventricular shape change in patients with aortic and mitral valvular regurgitation: assessment by Fourier shape analysis and global geometric indexes. AB - The normal cardiac cycle is associated with dynamic changes in left ventricular shape, which can be disturbed in disease states. To assess the influences of diastolic volume, percent ejected volume, and abnormalities of acute or chronic systolic loading on general and detailed chamber geometry, we studied dynamic shape change recorded by x-ray contrast ventriculography in both normal patients and those with aortic (AR) or mitral (MR) valve regurgitation. While both lesions increased diastolic volume, the character of load throughout ejection differed markedly. Detailed cavity geometry was assessed by a Fourier analysis technique and general shape by eccentricity and circularity indexes. Normal hearts, showed increased systolic elongation by all indexes. AR patients displayed a similar rise in eccentricity during ejection; however, the extent of shape change when measured by Fourier and circular indexes was reduced. In contrast, MR patients displayed enhanced systolic shape change, particularly in chamber elongation. Neither simple eccentricity of circular indexes adequately differentiated these shape abnormalities, whereas detailed Fourier geometric analysis precisely characterized the abnormalities of shape change in these two diseases. Relations between the extent of shape change and ejected volume for each patient group revealed significantly more systolic deformation with a different shape versus volume relation for the MR hearts as compared with AR and controls. Thus, while dynamic left ventricular shape is certainly influenced by the extent of volume change, it also varies independently from volume related to the specific nature of loading during ejection. PMID- 3335055 TI - Neuropeptide Y prevents the blood pressure fall induced by endotoxin in conscious rats with adrenal medullectomy. AB - Neuropeptide Y (NPY) is a vasoconstrictor peptide known to be present in the adrenal medulla, the terminal nerve endings, and in plasma. This study was designed to test whether NPY could prevent the acute blood pressure fall induced by endotoxin administration. Normotensive rats were subjected to adrenal demedullation on the right side and were either adrenalectomized or sham-operated on the left side. Eight to ten days later, NPY (0.07 microgram/min i.v.) or its vehicle were infused for 95 minutes into these conscious, semirestrained rats. The same experiments were performed with rats that received an infusion of epinephrine (0.1 microgram/min). These doses of NPY and epinephrine when given alone had no blood pressure effect. During the last 75 minutes of the 95-minute infusion, endotoxin (lipopolysaccharide Escherichia coli 0.111:B4, 10 micrograms/min i.v.) or its vehicle were administered. In rats with an intact adrenal gland, endotoxin failed to induce hypotension. In rats lacking a functioning adrenal medulla, however, endotoxin induced a pronounced mean blood pressure fall of 55 +/- 11.6 mm Hg (mean +/- SEM). This blood pressure drop could be prevented equally well with NPY and with epinephrine infusion and averaged 11 +/- 2.3 and 16 +/- 2.4 mm Hg, respectively, at the end of the experiment. Additional rats were biadrenalectomized and supplemented with an excess of glucocorticoids and mineralocorticoids. In these rats also, NPY markedly attenuated the blood pressure fall resulting from endotoxemia. These data taken together indicate that in conscious rats with no adrenal medulla, the acute blood pressure fall induced by endotoxin administration is greatly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335056 TI - Methionine-induced positive inotropic effect in rat heart: possible role of phospholipid N-methylation. AB - Perfusion of isolated rat heart with L-methionine produced a positive inotropic effect that was temporally preceded, as well as accompanied, by an increase of methyl group incorporation into N-methylated phospholipids of the myocardium. Maximal increase in contractile force development was associated with maximal methyl group incorporation. Both parameters showed a dose-related dependence on methionine and correlated positively (r = 0.965) upon regression analysis of the data. The presence of adenosine, L-homocysteine thiolactone and erythro-9-(2 hydroxy-3-nonyl) adenine in the perfusion medium inhibited the positive inotropic effect as well as the incorporation of methyl groups into phospholipids. Cycloleucine, an inhibitor of S-adenosylmethionine synthetase, also reduced the increase in contractility by methionine. Methionine-induced positive inotropic effect could be modulated by varying Ca2+ concentration in the perfusate and was inhibited by ryanodine, a blocker of sarcoplasmic reticular Ca2+ release. These observations indicate that L-methionine may serve as a powerful positive inotropic agent and suggest that phospholipid N-methylation plays an important role in functional activity of rat heart. PMID- 3335057 TI - Mechanics of cerebral arterioles in hypertensive rats. AB - Chronic hypertension is associated with hypertrophy of cerebral blood vessels. Previous studies of the mechanical properties of cerebral vessels in chronic hypertension have examined large cerebral arteries. The goals of this study were first to develop a method to examine vascular mechanics of cerebral arterioles in vivo and second to determine whether the stiffness of cerebral arterioles is altered in the presence of chronic hypertension. We calculated circumferential stress and strain of pial arterioles in age-matched, anesthetized stroke-prone spontaneously hypertensive rats (SHRSP) and in Wistar Kyoto rats (WKY) from measurements of pial arteriolar pressure, inner diameter, and wall thickness. Pial arteriolar pressure was measured with a servonull system. Smooth muscle of pial arterioles was deactivated with ethylenediaminetetraacetic acid (EDTA), and pressure-diameter relations were examined during step-wise reductions in pressure. Prior to deactivation of smooth muscle in 3-4-month-old rats, pial arteriolar pressure was greater in SHRSP than in WKY (110 +/- 4 versus 75 +/- 2 mm Hg [mean +/- SE]; p less than 0.05). Pial arteriolar diameter, which was measured at prevailing levels of pial arteriolar pressure, was less in SHRSP than in WKY (52 +/- 5 versus 63 +/- 3 microns; p less than 0.05). Following deactivation of smooth muscle, diameter of pial arterioles at 70 mm Hg of pial arteriolar pressure was similar in the two groups: 104 +/- 6 microns in SHRSP and 109 +/- 3 microns in WKY (p greater than 0.05). Wall thickness was 4.5 +/- 0.2 microns in SHRSP and 4.1 +/- 0.1 microns in WKY (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335058 TI - Maximal twitch tension in intact length-clamped ferret papillary muscles evoked by modified postextrasystolic potentiation. AB - A modified test of postextrasystolic potentiation achieved with a brief episode of rapid pacing followed by a 6-second pause (RPP maneuver) was used to evoke maximal force in isolated intact ferret right ventricular papillary muscles. Maximal RPP tensions were examined under length-clamped conditions and compared with the steady-state forces obtained when further increases in [Ca2+]o, did not further increase force and to the tensions recorded at the point of saturation of force when similarly length-clamped muscles were subjected to caffeine-induced tetanization. The results show that the calculated maximal twitch tension achieved with RPP is comparable to the 25-35 g/mm2 observed in intact single skeletal muscle fibers. The study also shows that the beat-to-beat decay of the potentiated contraction is exponential. While the amount of the constant fractional beat-to-beat decay is a function of [Ca2+]o, it is not influenced by length. During the decay of potentiation, the ratio of the potentiation of any beat divided by that of the previous beat is a constant, called (X). With certain assumptions, it is shown that (X) is a measure of the fraction of activator calcium taken up by the sarcoplasmic reticulum in each beat and, in the steady state, the fraction of activator calcium that comes from the sarcoplasmic reticulum. The (X) amounted to 33%, 50%, and 65% when [Ca2+]o was 1.25, 2.50, and 5.0 mM, respectively. Thus, at 1.25 mM [Ca2+]o, some two thirds of the total calcium required to activate the myofilaments comes from the extracellular compartment during excitation and only one third is contributed via release from the sarcoplasmic reticulum. In the region of optimal myofilament overlap, RPP force-length curves are remarkably shallow and almost indistinguishable from the sarcomere length-tension relation observed in skinned single cardiac cells. Tetanus plateau tensions are significantly smaller than RPP forces at any length, and the slope of the tetanus force-length curves is greater than that obtained with RPP. Thus, and by exclusion, we also suggest that caffeine may exert significant downstream inhibitory effects. PMID- 3335060 TI - Pericardial and cardiac pressure. PMID- 3335059 TI - Evidence for increased aortic plasma membrane calcium transport caused by experimental atherosclerosis in rabbits. AB - Several lines of evidence, including the reported ability of calcium channel blockers to prevent atherogenesis in cholesterol-fed rabbits, suggest that calcium mediates one or more of the pathologic changes in atherosclerosis. Moreover, it has long been known that calcium accumulates in atherosclerotic blood vessels. To test the hypothesis that a substantial fraction of this accumulated calcium is intracellular and to identify possible causes of this accumulation, calcium fluxes and contents were determined in aortic segments from cholesterol-fed rabbits and age-matched controls. A new method, based on 45Ca efflux experiments and computer-assisted kinetic analysis, was used to measure intracellular and extracellular calcium contents (nmol calcium/g wet wt tissue) and fluxes. Total intracellular calcium increased from 269 +/- 11.6 to 1,300 +/- 352 nmol/g in cholesterol-fed animals compared with controls (p less than 0.01). This change was sufficient to account for the observed increase in total tissue calcium from 4,190 +/- 211 to 5,240 +/- 477 nmol/g (p less than 0.05). Thus, the fraction of tissue calcium that is intracellular increased significantly from 0.065 +/- 0.006 to 0.223 +/- 0.048 (p less than 0.01) in experimental atherosclerosis. In addition, the data were quantitatively consistent with the hypothesis that these changes are brought about by a 4.8-fold increase in the plasma membrane calcium permeability of aortic smooth muscle cells. These results provide evidence that increased intracellular calcium is a possible mediator of cholesterol-induced atherogenesis. PMID- 3335061 TI - Cine magnetic resonance imaging after surgical repair in patients with transposition of the great arteries. AB - Cine magnetic resonance imaging (MRI) was used for postoperative evaluation of eight patients who underwent intra-atrial baffle procedure for surgical repair of D-transposition of the great arteries (D-TGA). Their ages ranged from 9 months to 8 years. Younger patients were sedated with chloral hydrate (80 to 100 mg/kg) orally. MRI was performed with use of a General Electric Signa system operating at a field strength of 1.5 tesla. A body or head coil was used depending on the size of the patient. Images were obtained by use of a technique of gradient recalled acquisition in steady state (GRASS) that utilizes a low flip angle and shorter repetition and echo times. Five patients had widely patent venae cavae and three had superior vena caval obstruction at the junction of the right atrium with a dilated azygos vein. There was no evidence of pulmonary venous obstruction in any of the patients. Right ventricular function was assessed in four patients and their ejection fractions ranged from 58% to 81%. Tricuspid and mitral regurgitation were observed in three and two patients, respectively. Both right and left ventricular outflow tracts were well visualized and showed no evidence of obstruction. Cine MRI is an entirely noninvasive, nonionizing, and safe procedure in young patients and appears to be a valuable alternative method for evaluating patients after surgical repair of D-TGA. With advancing technologies and an accumulation of experience with cine MRI, it appears that this new technique will play an important role in patient care for children with congenital heart disease. PMID- 3335062 TI - Electrical alternans and cardiac electrical instability. AB - We investigated the relationship between electrical alternans and cardiac electrical stability in a series of 20 dog experiments and in a pilot clinical study. Electrical alternans was detected in both the QRS complex and the ST-T wave by use of a novel multidimensional spectral technique. The magnitude of the alteration was expressed as the alternating electrocardiographic morphology index (AEMI), expressed as parts per million of waveform energy. Electrical stability in the dog preparations was assessed via the ventricular fibrillation threshold measurement, and in the clinical studies via programmed stimulation. In 10 dog experiments, systemic hypothermia resulted in a 60% decrease in ventricular fibrillation threshold (VFT) (p less than .0001) and a significant increase in both AEMI(QRS) form 3.7 +/- 3.0 to 1448 +/- 548 (p less than .0001) and AEMI(ST T) from 43.9 +/- 18.4 to 19,178 +/- 5579 (p less than .0001). In 10 dog experiments, transient coronary artery ligation also resulted in a 60% decrease in VFT (p less than .0001), an increase from 76.3 +/- 46.5 to 245 +/- 11 in AEMI(QRS) (p less than .05), and an increase from 842 +/- 505 to 1365 +/- 392 in AEMI(ST-T) (p less than .002). In 119 observations in 20 animal experiments, the rank correlation between VFT and AEMI(QRS) was -.30 (p less than .001), with that between VFT and AEMI(ST-T) being -.55 (p less than .0001). In a double-blind pilot clinical trial consisting of 23 studies in 19 patients, the result of electrophysiologic testing was used as an independent measure of cardiac electrical stability. Alternation in waveform morphology identified the inducible patient population with a sensitivity of 92%, a positive predictivity of 70%, and a specificity of 50% (p less than .05). We conclude that analysis of subtle beat to-beat variability in electrocardiographic morphology may provide a noninvasive measure of cardiac electrical stability. PMID- 3335063 TI - Identification of patients with sustained ventricular tachycardia by frequency analysis of signal-averaged electrocardiograms despite the presence of bundle branch block. AB - Previously, we have demonstrated distinguishing features in the fast Fourier transform (FFT) of signal-averaged electrocardiograms (ECGs) obtained during sinus rhythm in the absence of bundle branch block that differentiate patients with from those without sustained ventricular tachycardia (VT). The ECGs during sinus rhythm from many patients with sustained VT, however, exhibit intraventricular conduction abnormalities. Accordingly, this study was performed to determine whether the presence of bundle branch block during sinus rhythm precluded accurate identification of patients with sustained VT. Studies were performed in 28 normal subjects (group I) and 141 patients with organic heart disease grouped according to clinical characteristics. Group II comprised 40 patients without VT in whom the QRS duration during sinus rhythm was less than 120 msec. Group III included 21 patients without VT in whom the QRS duration during sinus rhythm was 120 msec or greater. Group IV comprised 43 patients with sustained VT having ECGs during sinus rhythm with QRS durations less than 120 msec. Group V included 37 patients with sustained VT in whom the QRS duration during sinus rhythm was 120 msec or greater. FFTs of the terminal QRS and ST segment of signal-averaged X, Y, and Z ECGs were computed. Transformed data were expressed as an FFT magnitude and the relative contribution and peak magnitudes of 20 to 50 Hz frequencies determined after first demonstrating that this FFT method was more appropriate, when compared with the energy spectrum, for analyzing ECG signals having a broad range of ST segment durations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335065 TI - Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia. AB - The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 [69 to 304] mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and "usual medical care" was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress. PMID- 3335066 TI - Antibiotic prophylaxis of experimental endocarditis after dental extractions. AB - In rats with catheter-induced sterile aortic valve vegetations we studied the efficacy of single-dose amoxicillin and single-dose erythromycin prophylaxis for the prevention of bacterial endocarditis after extractions of periodontally diseased teeth. Endocarditis after extractions occurred in 89% of control animals and was due to group G streptococci, to Staphylococcus aureus, or to both organisms. A single-dose of amoxicillin or erythromycin successfully prevented endocarditis due to these bacterial species. The analysis of the bacteremia (by culturing blood drawn 1 min after extraction on penicillinase-containing blood agar plates) indicated that amoxicillin did not influence the incidence or the magnitude of circulating group G streptococci and S. aureus, while erythromycin apparently suppressed them. However, when care was taken to eliminate blood erythromycin by a lysis-centrifugation process, the incidence and magnitude of bacteremia after erythromycin prophylaxis was similar to that in control rats. We conclude that single doses of amoxicillin and erythromycin successfully prevent experimental endocarditis after dental extractions. Since this prophylaxis was operative by mechanisms other than the prevention of the circulation of bacteria before seeding the valvular vegetations, it suggests that recommendations for prevention of bacterial endocarditis should not be aimed only at providing adequate antibiotic blood levels to suppress the bacteremia produced by the invasive procedure. PMID- 3335064 TI - Surgical ablation of ventricular tachycardia with sequential map-guided subendocardial resection: electrophysiologic assessment and long-term follow-up. AB - A new operative technique of sequential map-guided subendocardial resection (SER) was used in 45 consecutive patients for the treatment of sustained ventricular tachycardia due to coronary artery disease. This technique is characterized by map-guided SER or cryothermic ablation during normothermic cardiopulmonary bypass, followed by repeated sequences of programmed stimulation to assess adequacy of resection. The patients' mean age was 59 +/- 10 years and the mean left ventricular ejection fraction was 34 +/- 12%. Twenty-five (56%) patients had a history of myocardial infarction within the previous 2 months. After ventriculotomy, 34 patients (76%) had inducible monomorphic ventricular tachycardia. These patients underwent repeated sequences of ventricular tachycardia induction and mapping during normothermic bypass followed by successive SER or cryothermic ablation until sustained monomorphic ventricular tachycardia was no longer inducible. Twenty-seven patients had a total of 60 discrete, mappable tachycardias induced and seven patients had 10 discrete tachycardias that were too fast to accurately map. In the remaining 11 patients, no ventricular tachycardia was inducible after ventriculotomy and SER, which included all visually identifiable scar, was performed. The mean cardiopulmonary bypass time was 102 +/- 27 min. Forty-one of 45 patients (91%) survived to hospital discharge, and 35 of 41 patients (85%) had no inducible ventricular tachycardia at postoperative electrophysiologic evaluation performed in the absence of all antiarrhythmic drugs. The remaining six patients had no inducible ventricular tachycardia with drug therapy. All four operative nonsurvivors had refractory cardiac collapse preoperatively. Over 19 +/- 12 months of follow-up, there were four sudden cardiac deaths and no nonfatal recurrences of ventricular tachycardia. There were seven additional cardiac deaths. Actuarial cardiac survival was 0.57, and freedom from arrhythmic events was 0.76 at 42 months. Thus, in the absence of cardiogenic shock, the technique of sequential map-guided SER achieves: (1) a high operative survival with acceptable perfusion times, (2) excellent long-term arrhythmia control, and (3) survival comparable to that in patients with similar left ventricular function and no history of ventricular tachyarrhythmia. PMID- 3335067 TI - Implantation of balloon-expandable intravascular grafts by catheterization in pulmonary arteries and systemic veins. AB - The purpose of this investigation was to evaluate the efficacy and safety of implanting expandable intravascular stents in pulmonary arteries and systemic veins. Twenty-seven balloon-expandable grafts were placed in 13 mongrel dogs under anesthesia. A long sheath was introduced over a wire and catheter or dilator into the pulmonary artery or target vein. A collapsed stainless steel expandable mesh stent was placed over the balloon of an angioplasty catheter. The catheter with the mounted stent was advanced through the sheath. The stent expanded to the diameter of the balloon as the balloon was inflated, and remained expanded as the balloon was deflated. The stent was expanded further with a larger balloon in 11 instances. Eleven stents were placed successfully in pulmonary arteries (out of thirteen attempted), and 11 of 14 were installed in tributaries of the precava or postcava. Three inadvertent embolizations of the devices occurred. All three devices that embolized lodged in the pulmonary arteries and did not obstruct flow. Seven dogs were recatheterized at intervals ranging from 56 to 278 days. Twelve stents were patent and nonobstructive, and two were malpositioned, one of which was obstructed. Three animals were killed 2 months (two dogs) and 9 months (one dog) after the implantations. The stents (four in the pulmonary arteries and two in veins) were completely covered with neointima and were patent, without thrombosis. These stents hold promise for definitive dilation of congenital or postoperative vessel stenoses. PMID- 3335068 TI - Time-dependent change in electrophysiologic milieu after myocardial infarction in conscious dogs. AB - This study was designed to assess the time-dependent change in propensity to induction of malignant ventricular tachyarrhythmia after myocardial infarction. Instrumented conscious dogs were assessed during serial drug-free electrophysiologic studies over 26 +/- 9 days (range 17 to 35 days) after 2 hr occlusion-reperfusion of the left anterior descending coronary artery. Of the 19 animals studied, 11 continued to have sustained ventricular tachyarrhythmias inducible (group I) over this time period. In the eight remaining animals, spontaneous loss in the ability to induce sustained ventricular tachycardia occurred (group II). Myocardial infarct size in group I animals (18 +/- 8%) was significantly greater than that in group II dogs (12.5 +/- 5%; p less than .05). Even in group I animals, time-dependent changes occurred in the number of extrastimuli required to induce ventricular tachycardia and the frequency with which left ventricular stimulation was necessary. A differential pattern of time dependent changes in electrophysiologic variables was observed when comparing group I and II animals. The conduction time to the infarct zone was prolonged during follow-up in group I animals, while in group II animals this variable was unchanged. Repolarization time recorded in the border zone remained unchanged in group I animals, but it was significantly shortened in group II animals. In addition, ventricular effective refractory period in the infarct zone shortened over time in group I animals but did not change in group II animals. In conclusion, time-dependent changes occur in electrophysiologic variables that are associated with a progressive decrease in propensity to induction of ventricular tachycardia after myocardial infarction. A critical determinant of whether propensity to ventricular tachycardia resolves over time is size of myocardial infarction. PMID- 3335069 TI - The effect of changes in afterload on systolic bulging. AB - It has been previously shown that after acute coronary occlusion, the extent of systolic bulging is dependent on preload and the function of the remote nonischemic myocardium is influenced by the motion of the ischemic myocardium as well as by the loading conditions. To examine the isolated effects of changing afterload on the movement of acutely ischemic and nonischemic myocardium, seven open-chest, anesthetized dogs were paced from the left atrium at a rate of 100 beats/min after crushing of the sinus node. The pulmonary artery was perfused artificially and the left ventricular end-diastolic pressure (LVEDP) was carefully controlled with a right heart bypass system. Twenty minutes after occlusion of the left anterior descending artery, the peak left ventricular pressure (LVP) was adjusted to three levels (70, 90, and 110 mm Hg) by blood withdrawal or aortic constriction, while the LVEDP was kept constant (8.3 +/- 2.3 mm Hg). Segment length in the ischemic (IZ) and nonischemic zones (NZ) were measured with sonomicrometers and total, isovolumetric, and ejection systolic shortening (% delta L) were calculated. Changes in left ventricular minor-axis diameter were measured with diameter crystals. Increasing the peak LVP increased the LVP both at aortic valve opening and closing. To keep the LVEDP constant as peak LVP was increased, the cardiac output had to be decreased (p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335070 TI - Influence of compression rate on initial success of resuscitation and 24 hour survival after prolonged manual cardiopulmonary resuscitation in dogs. AB - The influence of chest compression rate on initial resuscitation success and 24 hr survival after prolonged manual cardiopulmonary resuscitation (CPR) was investigated in 26 morphine-anesthetized dogs (17 to 30 kg). After placement of aortic and right atrial micromanometers and induction of ventricular fibrillation, manual CPR was commenced immediately and continued for 30 min. One group of 13 dogs underwent manual CPR at a compression rate of 60/min, and the other group at a rate of 120/min. The compression durations in the two groups were not significantly different (51.7 +/- 1.8% at 60/min vs 51.6 +/- 1.9% at 120/min). No drugs other than sodium bicarbonate were administered during CPR. A maximum of three attempts was permitted to defibrillate the heart. Successfully defibrillated animals were followed for 24 hr, during which time no treatment, other than naloxone, was given to reverse the effects of morphine. Arterial blood pH, PCO2, and PO2 were not significantly different in the two groups throughout the CPR period. When compared with the compression rate of 60/min, the compression rate of 120/min produced more successfully defibrillated animals (12/13 at 120/min vs 2/13 at 60/min, p less than .002) and more 24 hr survivors (8/13 at 120/min vs 2/13 at 60/min, p less than .03). All 24 hr survivors were conscious and able to sit, stand, and drink normally. One 24 hr survivor in each group had difficulty walking. Improved survival with the high-rate compression technique was consistent with the significantly higher mean aortic (systolic and diastolic) and coronary perfusion pressures attained with high-rate compressions (all p less than .002). Although the clinical applicability of these findings has yet to be demonstrated, they provide empirical support for the recent decision to increase the chest compression rate for manual CPR recommended by the American Heart Association, and indicate that the hemodynamic and survival benefits of faster compression rates in this experimental preparation were not dependent on covariant alterations in compression duration. PMID- 3335072 TI - Quantitative cineangiographic analysis of ventricular volume and mass in patients with single ventricle: relation to ventricular morphologies. AB - With the use of biplane selective ventriculography, the ventricular volume, ejection fraction, and ventricular mass were evaluated in 28 patients with a single ventricle, and those with the left ventricular type (LV type, 12 patients) and right ventricular type (RV type, 16 patients) were compared. There were no significant differences in terms of age, hemoglobin, systemic oxygen saturation, or pulmonary-to-systemic flow ratio in the two groups. No patients with atrioventricular valve regurgitation were included. The ventricular cavity volume was calculated by the area-length method. The ventricular mass volume was determined as the shell volume created by subtracting the ventricular cavity volume from the total ventricular volume calculated by adding the free wall thickness to the chamber dimensions. The ventricular mass volume was converted to mass by multiplying by the gravity of the heart muscle. There was no significant difference between patients with the LV type and RV type of single ventricle with respect to the end-diastolic ventricular volume (188 +/- 53 and 179 +/- 61 ml/m2 in LV and RV types, respectively), end-systolic volume (88 +/- 31 and 84 +/- 27 ml/m2), or ejection fraction (0.54 +/- 0.06 and 0.52 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335071 TI - Quantitative analysis of right and left ventricular infarction in the presence of postinfarction ventricular septal defect. AB - To quantitate the amount of right and left ventricular infarction in patients dying with postinfarction ventricular septal defect (PIVSD), hearts from 54 patients with anterior or inferior myocardial infarction were studied at autopsy. Fifteen hearts had myocardial infarction with PIVSD and 39 hearts had infarction without PIVSD and were used as a comparison group. All infarcts were sized histologically and the percent of each ventricle infarcted was quantitated by computer-assisted planimetry. The pathologic substrate for PIVSD was diffuse coronary artery disease with acute thrombosis resulting in transmural confluent infarction. Within the PIVSD group, there was significantly more left ventricle involved in anterior infarctions than in inferior infarctions (p less than .04). Conversely, there was more right ventricular infarction in inferiorly located myocardial infarctions with resulting PIVSD (p = .059). When infarctions resulting in PIVSD were compared with infarctions not resulting in PIVSD, the PIVSD group was characterized by larger left and right ventricular infarcts irrespective of infarct location (p less than .003). The incidence of right ventricular infarction was 100% in the PIVSD group (p less than .0001). Twelve of the 15 patients with PIVSD (80%) developed cardiogenic shock within 48 hr of septal rupture. The high incidence of shock and the rapid deterioration may have been secondary to right ventricular infarction in these patients. Therefore, infarcts resulting in PIVSD and subsequent death are characterized by a high incidence of right ventricular infarction. Significantly more infarction of the right ventricle is seen in either anterior or inferior infarctions resulting in PIVSD compared with infarctions not resulting in PIVSD. PIVSD complicating inferior infarctions is associated with the greatest amount of right ventricular infarction. PMID- 3335073 TI - Changes in myocardial repolarization in patients undergoing balloon valvuloplasty for congenital pulmonary stenosis: evidence for contraction-excitation feedback in humans. AB - Alterations in ventricular loading conditions lead to changes in action potential duration and arrhythmias via contraction-excitation feedback; a decrease in load leads to prolongation of repolarization. To determine whether changes in right ventricular load alter ventricular repolarization in man, the corrected QT interval, a measure of overall ventricular repolarization, was measured in 32 patients before and after valvuloplasty for pulmonary stenosis. Right ventricular systolic pressure decreased (82.5 +/- 30.7 to 40.5 +/- 9.5 mm Hg, p less than .001) and the QTc increased concurrently (409.1 +/- 24.3 to 440.7 +/- 28.0 msec, p less than .001) after successful valvuloplasty. The increase in QTc was most marked for those patients with a greater than 30 mm Hg decrease in right ventricular pressure (40.0 +/- 23.3 vs 16.3 +/- 21.3 msec, p = .006). In a subset of seven patients in whom monophasic action potentials were recorded, monophasic action potential duration, a measure of local repolarization, was prolonged (230.0 +/- 24.3 vs 216.9 +/- 21.9, p less than .001) after successful valvuloplasty, confirming that the QTc prolongation reflected changes in local ventricular repolarization. In addition, during nine acute right ventricular outflow tract occlusions in a subset of six patients, monophasic action potential duration shortened (206.6 +/- 17.6 vs 221.7 +/- 20.9 msec, p less than .01) and early afterdepolarizations developed consistent with contraction-excitation feedback. These data suggest that, in humans, changes in mechanical load are associated with changes in ventricular repolarization consistent with contraction excitation feedback. PMID- 3335074 TI - Value and limitations of Doppler echocardiography in the quantification of stenotic mitral valve area: comparison of the pressure half-time and the continuity equation methods. AB - Two Doppler methods, the pressure half-time method proposed by Hatle and the method based on the equation of continuity, were used to estimate stenotic mitral valve area noninvasively, and the accuracy of these methods was examined in patients with and without associated aortic regurgitation. Mitral valve area determined at catheterization by the Gorlin formula was used as a standard of reference. The study population consisted of 41 patients with mitral stenosis, and 20 of the 41 patients had associated aortic regurgitation. According to the equation of continuity, mitral valve area was determined as a product of aortic or pulmonic annular cross-sectional area and the ratio of time velocity integral of aortic or pulmonic flow to that of the mitral stenotic jet. Mitral valve area was determined by the pressure half-time method as 220/pressure half-time, the time from the peak transmitral velocity to one-half the square root of the peak velocity on the continuous-wave Doppler-determined transmitral flow velocity pattern. The pressure half-time method tended to overestimate catheterization measurements, and the correlation coefficient for this relation was .69 (SEE = 0.44 cm2). The correlation coefficient improved to .90 when the patients with associated aortic regurgitation were excluded. Mitral valve areas determined by the continuity equation method correlated well with catheterization measurements at a correlation coefficient of .91 (SEE = 0.24 cm2), irrespective of the presence of aortic regurgitation. The ratio of the time-velocity integral or aortic or pulmonic flow to the time-velocity integral of mitral stenotic jet also correlated well with mitral valve area determined by catheterization at a correlation coefficient of .84 (SEE = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335075 TI - The contribution of magnetic resonance imaging to the evaluation of intracardiac tumors diagnosed by echocardiography. AB - MAgnetic resonance (MR) imaging was performed in 14 patients with intracavitary cardiac tumors diagnosed by echocardiography. Except in the patients whose echocardiograms were diagnostic of atrial myxomas, this modality contributed important additional anatomic information regarding the tumor's relationship to the normal intracardiac structures and/or its extension to the adjacent vascular and mediastinal structures. The MR findings correlated extremely well with the findings in all 12 patients who underwent surgical exploration or postmortem examination, and in the other two patients, MR guided the decision to obtain transvenous biopsy samples of their right heart masses. PMID- 3335076 TI - Androgens inhibit proliferation of human peripheral blood lymphocytes in vitro. AB - The effect of sex hormones on human lymphocytes was examined in vitro on cell cultures of human peripheral blood mononuclear cells (HPBM). Cells were stimulated using T- and B-cell mitogens, and hormones in physiological (nM) or pharmacological (microM) concentrations were added. Proliferation was determined by measuring the incorporation of tritiated thymidine. It was found that both testosterone and dihydrotestosterone, in physiological concentrations, can attenuate DNA synthesis. The effect was dose dependent in that pharmacological concentrations of both testosterone and dihydrotestosterone caused a strong inhibitory effect on proliferation of in vitro cultured HPBM. However, cell cultures of a few individuals were insensitive to the androgens even at pharmacological concentrations. Also, no difference could be detected in the response between cultured cells of females and males. Although a slight reduction in antibody production was evident in pokeweed mitogen-stimulated cultures, in the presence of both testosterone and dihydrotestosterone, it was, however, not statistically significant. PMID- 3335077 TI - Lymphokine-activated killer cell lysis of human neuroblastoma cells: a model for purging tumor cells from bone marrow. AB - Evidence is presented that neuroblastoma tumor cells in host bone marrow is susceptible to autologous lymphokine-activated killer cells (LAK). Thus, immunologic purging of bone marrow with LAK may be considered as a tool in the arsenal of bone marrow purging-for autologous bone marrow transplantation. PMID- 3335078 TI - Nurses aiding smokers therapist program: nursing school intervention model. PMID- 3335079 TI - Pulmonary tumor colony formation following i.v. inoculation of six human colorectal carcinoma xenografts in young gnotobiotic athymic mice. AB - The lung colonizing potential of 6 xenografted human colorectal adenocarcinomas following tail vein inoculation of tumor cell suspensions into gnotobiotic 3-4 week-old congenitally athymic mice was investigated. One of the lines, CRCo2, was of particular interest, as apparently distinctive lung colonizing phenotypes, large (greater than 2.5 mm diameter) and small (less than 1 mm diameter) colonies were identified, and variant lines with greater, equal, or lesser ability to grow in the lungs relative to the sc tumor of origin were observed. Another line, CRCo1, was also able to grow well in the lungs following tail vein inoculation, but subsequent cycles of lung tumor recovery and reinoculation i.v. did not result in an enhancement of the tumor's lung colonizing ability relative to the initial i.v. inoculation of the sc carried tumor. Scattered lung colonies were observed following i.v. inoculation of sc carried xenografts in three of the four other lines, but we could not consistently recover lung colonies with these tumors. The data are in accord with the clinical observation that pulmonary metastasis is not a high frequency event in human colorectal carcinoma, illustrating the selective nature and experimental utility of this model of metastasis. Further, there were indications of the inefficient and/or random nature of the metastatic process in some of the tumors, while in others, evidence for both effectively higher and lower metastatic variants were found, as might be predicted in heterogeneous tumor cell populations. PMID- 3335080 TI - Is adjuvant treatment with vinblastine effective in reducing the occurrence of distant metastasis in limited squamous cell lung cancer? A randomized study. AB - In order to study the usefulness of treatment with vinblastine (VLB) in the prevention of cancer metastasis in squamous cell lung cancer, 50 patients with locoregional disease were randomized to receive either locoregional RT alone (group A) or a weekly intravenous bolus injection of VLB (6 mg/m2) concurrently with and after locoregional radiotherapy (RT) (55 Gy in 6 weeks) until the appearance of metastases (group B). Neither the incidence of death with metastases, metastasis-free survival (MFS) nor overall survival (S) were significantly affected by treatment with the drug. However, due to the limited number of patients in each group, the power of the statistical test was such to allow only the detection of differences in MFS and S to or more than 80 per cent at the P = 0.05 level. Local tumor response was significantly superior in group B (P less than 0.05). Acute toxicity (dysphagia, myelosuppression) during RT was significantly worse in group B. During long-term therapy with VLB, mild polyneuropathy developed in the majority of patients in group B. Furthermore, seven patients discontinued treatment with VLB during maintenance due to compliance (4) and excessive neurotoxicity (3). This treatment schedule with VLB is not recommended for patients with locoregional squamous cell lung cancer as significant toxicity is present during and after RT and significant increase in MFS and S is lacking. Because of an apparent increase in local response, the combination of VLB and RT merits further investigation in those tumors where local tumor control is crucial. PMID- 3335083 TI - Symposium: The Knee Society proceedings of 1987. PMID- 3335082 TI - Endothelialization of embolized tumor cells during metastasis formation. AB - The reaction of the endothelial barrier to tumor cell extravasation has been studied using electron microscopy. The model system was pulmonary metastases produced by intravenous injection of B16-F10 melanoma cells. A striking difference was observed in the behavior of the endothelial lining of arterioles versus that of capillaries. In capillaries, partial retraction of endothelial cells took place following the attachment of tumor cells. The tumor cells then immediately attached to the basement membrane and the basolateral surface of the retracted endothelial cells. The endothelial cells extended to cover the tumor cells prior to complete extravasation. In the arterioles, on the other hand, endothelial retraction did not occur following tumor cell attachment. Instead the attached tumor cell emboli became encompassed by endothelial cells, outgrowing from the intact endothelial lining of the arteriole. Owing to the proliferation of the tumor cells, tumor colonies encompassed by endothelial cells expanded within the lumen. When these intravascular growths completely filled the lumen, the tumor cells extravasated from the vessel only after the original endothelial layer became mechanically disrupted and the tumor cells thereby came into contact with the basement membrane. PMID- 3335081 TI - Molecular identification of lectin binding sites differentiating related low and high metastatic murine lymphomas. AB - We have previously shown that differences in cell surface carbohydrates can be detected in related murine tumor lines of varying metastatic capacity using plant lectins such as soybean agglutinin (SBA) or Vicia villosa (VV) but not concanavalin A (ConA). Here we show that weakly metastatic Eb cells bind SBA via four glycoproteins and one GL2-like glycolipid. The major high-affinity SBA binding component of weakly metastatic ESb-MP cells was a glycoprotein of 210-220 kd. Highly metastatic ESb cells also expressed this protein but the oligosaccharide side chains were altered in such a way that SBA-binding was completely lost while ConA and peanut agglutinin (PNA) binding remained similar. Quantitative binding studies using iodinated lectins indicated that SBA binding of ESb cells could only be detected at lectin concentrations greater than 75 micrograms/ml. The role of altered carbohydrates in metastasis is discussed. PMID- 3335084 TI - Long-term results of conservatively treated medial collateral ligament injuries of the knee joint. AB - The purpose of the study was to determine the long-term healing potential of nonoperatively treated isolated sprains of the medial collateral ligament (MCL) of the knee joint. A multidimensional follow-up analysis was performed an average of nine years after injury, with 54 patients with Grade II sprains (partial tear of the MCL) and 27 patients with Grade III (complete tear) sprains. The methods used included four standardized knee scoring scales for subjective, objective, functional, and roentgenographic evaluations, as well as isokinetic and isometric strength evaluations. The outcome in Grade II sprains of the MCL was generally good, even though some residual medial laxity was common. In Grade III sprains the outcome was much worse, with a high frequency of persisting medial instability, dysfunction of the anterior cruciate ligament, muscle weakness, and posttraumatic osteoarthritis of the injured knee. Grade II sprains of the MCL respond acceptably to nonoperative treatment, whereas in Grade III sprains such treatment is not the method of choice. PMID- 3335085 TI - Popliteus tendon rupture. Case report and review of the literature. AB - A 23-year-old man sustained an isolated popliteus tendon rupture while pushing a car. The diagnosis was established with the use of arthroscopy, electromyography, and Cybex testing. After the patient failed to respond to conservative therapy, the tendon rupture was surgically repaired. The patient had an uneventful recovery and returned to his preinjury level of athletic activity. Although popliteus tendon tenosynovitis as well as injury to the popliteus in association with other ligamentous knee injuries has been described, neither an isolated popliteus tendon rupture nor an arthroscopic evaluation of a popliteus tendon rupture has been reported. PMID- 3335086 TI - A new jig for proximal tibial osteotomy. AB - The result of a proximal dome-shaped tibial osteotomy depends greatly on the accuracy of the surgical procedure. Contemporary jigs still are not sufficiently precise to provide three-dimensional guidance. A new jig was designed to place the pins correctly in both coronal and sagittal planes and to provide anterior advancement of the distal fragment of the tibia. The results obtained with this relatively simple device are predictable and reproducible. PMID- 3335087 TI - Alignment and long-term clinical results of a semiconstrained knee prosthesis. AB - In knee arthroplasty, component malpositioning seems to be a fundamental cause for failure. The degree of malpositioning is important. To investigate this degree, 86 of 137 knee arthroplasties performed with the Townley semiconstrained bicondylar prosthesis were examined after a mean follow-up period of 6.5 years (range, 5.0-8.5 years). Five arthroplasties were excluded because of aseptic loosening, but none of these showed malalignment in postoperative roentgenograms. Clinical results and the patients' reports on deterioration of prosthetic function were correlated with positioning of the prosthetic components. Total alignment between 6 degrees of varus and 7 degrees of valgus was associated with good clinical results. Total alignment of more than 7 degrees of valgus, anterior tilting of the tibial component, or positioning of the femoral component in more than 12 degrees of valgus correlated with relatively poor clinical results. PMID- 3335088 TI - Total knee arthroplasty in a patient with congenital dislocation of the patella. Case report. AB - A 63-year-old man with bilateral congenital dislocation of the patella developed severe osteoarthritis of his knee joints. Bilateral total knee arthroplasty was performed without an attempt to correct the dislocated patella and extensor mechanism. Four years later the patient had excellent, painless function of his knee joints with stability and excellent quadriceps strength. PMID- 3335089 TI - Arthroscopic training using pig knee joints. AB - Arthroscopy can be a difficult technique for the resident and staff physician to master. Various models have been constructed to allow the training arthroscopist time to perfect the technique. Aside from cadaver knees, there has been only one report of a successful in vivo training model. Sectioned pig knee joints for teaching and practicing arthroscopy satisfy many of the points suggested by others: they are cost effective, easy to use, mount and store, provide a realistic approach, and have comparable structural anatomy to the human knee. PMID- 3335090 TI - Unicompartmental knee arthroplasty. Ten- to 13-year follow-up study. AB - In the past decade, two concepts have caused considerable controversy in orthopedic surgery of the knee. Some orthopedic centers contend that osteotomy of the tibia is the procedure of choice for unicompartmental gonarthrosis of the knee and resist the concept of unicompartmental arthroplasty. The other concept is that if unicompartmental arthroplasty is necessary, the entire joint should be replaced, since the uninvolved compartment may develop arthritis in the future. This concept is illogical and contrary to the basic orthopedic principle of preserving normal structures whenever possible. It is obvious that joint replacements may not last the life of the patient and the need for revision must be considered; therefore, the original procedure should preserve as much bone stock as possible. The purposes of this review of unicompartmental replacement are to resolve these questions with data on long-term results of unicompartmental arthroplasty compared with data on high tibial osteotomy, to evaluate the cause of failures, and to improve future results. Eighty-seven consecutive unicompartmental arthroplasties were performed between November 1972 and April 1976. There were 60 knees available for study, with a minimum ten-year (average, 11-year) follow-up period. The results were evaluated using the Hospital for Special Surgery rating system, with 30 excellent, eight good, four fair, and 18 poor results. Seventy percent of the patients had satisfactory results, and pain relief was accomplished in 86.6% of patients. Of the 21 failures, the majority were due to material or technical problems and improper selection of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335092 TI - Comparative analysis of ankle arthroplasty versus ankle arthrodesis. AB - In a retrospective study of 41 patients with total ankle arthroplasty (25 patients) and ankle arthrodesis (18 patients), the mean follow-up period was 3.8 years for total ankle arthroplasties and 3.3 for ankle arthrodeses. Sixteen of the 23 ankle arthroplasty patients, and 17 of the 18 arthrodesis patients had good or excellent results. Total ankle arthroplasty was successful in patients with rheumatoid arthritis, but not posttraumatic arthrosis. Total ankle arthroplasty is indicated in rheumatoid patients with severe ankle involvement who have not responded to medical management. It also may be used in the elderly or debilitated patients who will place minimal stress on the ankle. The elderly may not tolerate the prolonged immobilization or repeated operations that fusion may require. Total ankle arthroplasty should not be used in young patients with posttraumatic arthrosis. PMID- 3335091 TI - The subtalar sprain. A roentgenographic study. AB - Subtalar and ankle sprains are more frequently associated than previously suspected. In this study, 40 patients were analyzed, using subtalar arthrograms and ankle stress films. Thirty-two of the 40 patients had a rupture involving components of both subtalar and ankle capsuloligamentous structures. If ignored or improperly treated, these lesions may develop into a sinus tarsi syndrome or a chronically painful and unstable ankle. Negative stress films in the presence of a clinically serious ankle injury should arouse suspicion of an underlying subtalar sprain, as demonstrated in six patients with positive arthrograms. PMID- 3335093 TI - Subjective results of hallux rigidus following treatment with cheilectomy. AB - The records of 58 patients who had hallux rigidus and were treated with cheilectomy between 1977 and 1984 showed the following results: 53.4% completely satisfactory, 19% mostly satisfactory, 27.6% unsatisfactory. No deterioration of results with time was apparent. When the results were analyzed in relation to the degenerative changes that were evident in the preoperative roentgenograms, the failure rate was increased from 15% with Grade I changes to 37.5% with Grade III changes. Cheilectomy is the procedure of choice in patients with hallux rigidus and Grade I changes. PMID- 3335094 TI - Amputation of the great toe. A clinical and biomechanical study. AB - Clinical and biomechanical observations were made on otherwise normal feet in ten patients, who had had amputations for pollicization of the great toe. Measureable changes were demonstrated in the patients' gait pattern and in force plate data. The center of pressure was noted to shift from beneath the second metatarsal head on the normal side to beneath the third metatarsal head on the amputated side. The velocity of movement of the center of pressure slowed significantly in the metatarsal head region of the operated side, which secondarily resulted in an increased loading of the metatarsal region. The progression of the center of pressure was noted to be beneath the third metatarsal head region on the involved side, instead of progressing medially and distally toward the first web space. Clinically, the operated foot demonstrated slight thickening beneath the second and third metatarsal heads but no significant abnormal callus formation developed. The patients' shoes all showed increased lateral wear on the amputated side. From a functional standpoint, the patients had little or no disability from loss of the hallux. PMID- 3335095 TI - Treatment of femoral shaft fractures with the Brooker-Wills interlocking intramedullary nail. AB - Fifty femur fractures were treated with the Brooker-Wills intramedullary locking nail. The indications included subtrochanteric, subisthmal, segmental or comminuted acute fractures or nonunions, and intramedullary shortening procedures. Eighteen technical problems in 13 (26%) patients were encountered during insertion of the nail. The incidence of technical problems was high early in the series and in procedures done with the patient in the supine position. Adverse clinical results from technical errors occurred in two patients. Most technical errors seem avoidable with careful technique. The mean healing time was only 12.1 weeks and there were four nonunions (8%). One patient had a 10 degrees malunion, four patients had 1-2 cm of shortening, and there were two late device fractures. No patients had rotational malalignment or deep infections. The results and complication rate are comparable to those reported for other interlocking systems. The Brooker-Wills nail is useful for treatment of complex femur fractures and has been effective in preventing malrotation, angulation, and excessive shortening. PMID- 3335096 TI - Total condylar III knee prosthesis. Long-term follow-up study. AB - The total condylar III knee prosthesis (TCP III) is a constrained, unlinked knee that provides medial and lateral stability through a rectangular tibial post and a high femoral box. Thirty-one knees were implanted in 25 patients. There were 17 primary arthroplasties and 14 revisions. The average follow-up period was 3.8 years. The average arc of motion was improved from 63 degrees to 97 degrees. This resulted in 77% good and excellent results. There were five failures (16%), all of which occurred in the revision group. These results compare favorably with results of constrained prostheses; however, the deformity in this group was quite severe. The major indications for use of TCP III would be medial ligament loss, severe valgus or combined deformities, or cases of unstable revision in which a surface arthroplasty will not suffice. The prosthesis should not be used in cases that demonstrate massive bone loss. In those cases, the prosthesis should have a weight-bearing intramedullary stem to transfer stress lines to cortical bone. PMID- 3335097 TI - Local delivery of antibiotics via an implantable pump in the treatment of osteomyelitis. AB - Twenty-one patients with osteomyelitis were treated with surgical debridement and local antibiotic therapy. Amikacin (19 patients) or netilmicin (2 patients) was delivered locally via a pump implanted subcutaneously. The outflow catheters were led from the pump subcutaneously to the infected area and placed in the defect created by the surgical debridement. The pump was refilled at intervals, on an outpatient basis. The pump was surgically removed at the conclusion of therapy. Follow-up evaluation was for 12-27 months. The duration of hospitalization was five to 52 days (mean, 23 days). The infusions were sustained for 32-140 days (mean, 63 days). Systemic levels of antibiotics were always below acceptable trough levels. Levels in the wound drainage of the 11 patients who drained after operation were always greater than the upper limit of the assay. Nephrotoxicity and ototoxicity were determined using pre- and posttherapy creatinine clearances and audiograms. Two patients exhibited minimal nephrotoxicity (creatinine clearance of 66 ml/minute and 55 ml/minute; normal, 70 ml/minute). There were no other adverse effects of the antibiotics. Sixteen patients have not drained since removal of the pumps. PMID- 3335098 TI - Aspergillus discitis. Report of two cases and review of the literature. AB - Aspergillus discitis is a rare disease that usually occurs in immunocompromised hosts. In the one case reported in the orthopedic literature surgical debridement was required. Two additional cases, which occurred in intravenous drug abusers, are reported here. One case is unique in the orthopedic literature in that eradication of the disease occurred with chemotherapy alone. PMID- 3335099 TI - Management of civilian gunshot fractures of the extremities. AB - One hundred thirty-two gunshot fractures of the extremities in 126 patients were studied retrospectively and followed until clinical union from January 1980 to January 1985. Civilian handgun missile velocities have increased; should the trend continue, treatment protocols will need to be modified. All uncomplicated low-velocity gunshot fractures, less than 615 m/second, (2000 feet/second), can be managed conservatively, with superficial debridement, surgical cleansing, immobilization, and antibiotics. Seventeen orthopedic procedures were performed; specific treatment was dictated by the type or location of the fracture caused by the missile. One hundred thirty-two fractures were treated with antibiotic therapy, 80 intravenously and 52 oral administration. Only two infections were encountered, both in the oral therapy group. No statistically significant advantage of intravenous over oral administration was found. Emergency room debridement along with oral antibiotic therapy for uncomplicated low-velocity gunshot fractures not requiring operative fixation yielded results comparable to those of hospitalization, with dramatically reduced medical costs. PMID- 3335100 TI - A simplified technique of distal femoral screw insertion for the Grosse-Kempf interlocking nail. AB - Failure accurately to determine distal femoral screw hole position can sometimes prolong operating time for placing an interlocking Grosse-Kempf rod. The described technique allows the distal femoral screw holes to be localized accurately with minimal radiation exposure. This technique utilizes readily available instruments and is not technically demanding. PMID- 3335101 TI - Subtalar fusion for isolated subtalar disorders. Preliminary report. AB - Retrospective observations on subtalar fusions performed for isolated subtalar disorders in 11 feet were performed to determine whether a satisfactory result could be obtained without significant changes to the talonavicular and calcaneocuboid joints. Preoperative diagnoses included five feet with degenerative arthritis secondary to a calcaneal fracture, four feet with a talocalcaneal bar, one foot with a degenerative subtalar arthropathy of unknown cause, and one foot with an unstable subtalar joint secondary to a peroneal tendon rupture. The average follow-up period was 41.5 months (range, 23-103 months). The hindfoot was fused in a average of 6 degrees of valgus. The feet maintained approximately 50% of their transverse tarsal motion, compared with the contralateral side. No foot developed hypermobility of any tarsal joint. Three feet fused for degenerative joint disease developed very mild talar beaking, and two feet fused for a tarsal coalition developed a mild progression or increase in talar beaking. Three feet demonstrated very minimal osteophyte formation at the calcaneocuboid joint. Functional and pain ratings for patients who had fusions for talocalcaneal bars or degenerative joint disease were good to excellent. Minimal radiographic changes at the talonavicular and calcaneocuboid joints secondary to increased stress brought about by the fusion did not seem to be clinically significant. Isolated subtalar fusion for lesions limited to the subtalar joint, which includes talocalcaneal bars, is a satisfactory method of treatment. PMID- 3335102 TI - Salvage of infected total knee arthroplasty. AB - Between 1981 and 1986, 25 patients with 26 infected total knee arthroplasties (TKAs) were treated with complete debridement of the knee, prosthetic removal, and six weeks of intravenous antibiotics, followed by insertion of a new prosthesis. The patients were followed for 12-57 months (average, 29 months). There was no evidence of residual infection at follow-up examination in any case. Applying the Hospital for Special Surgery knee rating system, 12 patients (50%) were rated excellent, six patients (25%) good, two patients (9%) fair, and four patients (6%) poor. Of the six patients with fair and poor results, five had reduced scores due to joint problems unrelated to the infected TKA. Fourteen patients had no pain at follow-up examination, and four had only slight pain. Nine patients had no limp, ten had a slight limp, one had a moderate limp, and the remainder either had a severe limp or were bedridden due to other joint problems. Eight patients could walk an unlimited distance and four could walk at least one-half mile. Twenty-one knees had a range of flexion greater than 90 degrees. Three patients had extensor lags of 20 degrees or greater. Only one patient required bracing for ambulation. PMID- 3335104 TI - The role of continuous passive motion following total knee arthroplasty. AB - A retrospective study of 94 knees with postoperative continuous passive motion (CPM) therapy was compared with a control group of 116 knees with no postoperative CPM following kinematic condylar total knee arthroplasty (TKA) performed in 1983. The diagnoses were similar in both groups, with osteoarthritis in 167 knees, rheumatoid arthritis in 34 knees, osteonecrosis in four knees, traumatic arthritis in four knees, and psoriatic arthritis in one knee. Average flexion at hospital discharge was 87.7 degrees in the control group and 90.2 degrees in the CPM group (p less than 0.02). Seventy-four percent of the CPM group and 60% of the control group had achieved 90 degrees of flexion by the time of hospital discharge. The number of days to achieve 90 degrees averaged 10.3 in the control group and 7.7 in the CPM group (p less than 0.001). There was no significant difference in flexion at two or three months or at one year after operation between the two groups. Five knees in the control group and one in the CPM group required manipulation. The duration of hospitalization was not significantly different between the two groups. Hemoglobin levels, operative blood loss, and transfusion requirements were not significantly different. Patients with CPM following TKA achieve motion earlier than those without CPM, but ultimate motion and complications are not affected. PMID- 3335103 TI - The effect of cryosurgery and polymethylmethacrylate in dogs with experimental bone defects comparable to tumor defects. AB - The effects of liquid nitrogen (LN) and polymethylmethacrylate (PMMA) on normal bone, bone graft incorporation, and reossification were evaluated by simulating a tumor in dogs with experimental bone cavity. Ten skeletally mature mongrel dogs (20 femora) were divided into three groups: Group I, controls; Group II, LN (with and without bone graft); and Group III, PMMA (with and without LN). Roentgenograms, whole-mount histology, and tetracycline fluorescence studies were performed on the distal femur. Correlation of these studies showed that (1) marked trabecular and bone necrosis, extending 7-12 mm around the circumference of the cavity, developed by three and seven weeks after LN but no bony necrosis occurred after PMMA; (2) the pattern of reossification following cryosurgery was delayed and abnormal, demonstrating increased calcification and metaplastic bone formation; (3) cryosurgery decreased the rate of bone graft incorporation; (4) the cryonecrotic rim following cryosurgery correlated with an abortive attempt at peripheral reossification; and (5) cryosurgery had no effect on the articular cartilage. Cryosurgery is effective in causing bone necrosis, whereas PMMA is not, and the pattern of reossification is delayed and altered by freezing. This study suggests that microvascular thrombosis with subsequent ischemic infarction of bone is a major cause of bone necrosis following cryosurgery. PMID- 3335105 TI - The mechanical stability of various noncemented tibial components. AB - Four different porous-coated tibial prosthetic implants were tested for their mechanical stability following implantation into paired cadaver tibias: Porous Coated Anatomic (PCA), Miller-Galante, Whiteside, and Anatomic Modular Knee (AMK). Following implantation the test sample was loaded eccentrically over the medial tibial plateau at 40 cycles per minute for 300,000 cycles, using an MTS machine. This represents the number of steps taken by the average person in a six to 12-month period. Load varied sinusoidally from 5 to 115 kg. Subsidence and lift-off of the tibial plate from its bony bed was recorded for each implant, using linear variable differential transformers. The greatest degree of mechanical stability was observed with the AMK design, which is secured to the bone bed using four peripherally placed 6.5-mm cancellous screws. No motion in excess of 100 micron was observed. The central-stemmed Whiteside design and the cortical screw fixated Miller-Galante designs provided slightly less stability, each demonstrating approximately 200 micron of lift-off on the unweighted side. The PCA design exhibited the greatest amount of micromotion with subsidence and lift-off displacements of 500 micron (0.5 mm). PMID- 3335106 TI - Presidential address to The Knee Society. Choices and compromises in total knee arthroplasty. AB - The art and science of total knee arthroplasty (TKA) has come a long way in the last 15 years. TKA has become a highly regarded and frequently recommended procedure. However, some of the uncertainties of the past about selection of design continue today, albeit in modified form. Ten years ago the surgeon was faced with a sometimes bewildering choice of prosthetic devices for which there were various indications. The same remains true today. PMID- 3335107 TI - Mechanisms of failure in total knee arthroplasty. AB - The major mechanisms of failure in total knee arthroplasty are loosening, instability, sepsis, extensor mechanism power loss, poor range of motion, bone fractures, and prosthesis fracture. These are, for the most part, within the surgeon's control. Prosthetic alignment is the most important factor influencing postoperative loosening and instability. PMID- 3335108 TI - Survivorship analysis and results of total condylar knee arthroplasty. Eight- to 11-year follow-up period. AB - This study deals with survivorship of total condylar knee arthroplasties in 87 consecutive patients (112 knees) with follow-up periods of up to 11 years. The end point of the survivorship was defined as: (1) the need for revision due to septic or aseptic loosening; (2) roentgenographic loosening evidenced by a shift of component position; or (3) radiolucency extending under the condyle of the tibial component and partially along the peg, when associated with clinical symptoms. Life table calculations predict 88.7% survivorship of total condylar knee arthroplasty. Using revision for septic or aseptic loosening and recommendation for surgery as an end point, the survivorship was 94.1% 11 years after operation in this series. Seventy-two patients (90 knees) of 87 were available for clinical and roentgenographic study at eight to 11 years. Eight patients (12 knees) had died and seven patients (ten knees) were lost to follow up study. The results were excellent to good in 93%, fair in 3%, and poor in 4%. Roentgenographic evaluation revealed well-fixed components in 36 knees (40%). Radiolucencies of varying degrees were present in 54 knees (60%). Of the 54 knees, seven had radiolucency under the tibial condyle in Zones I-IV and partially along the peg in Zones V and VI. Two knees had component loosening, one with a loose patella and the other a loose tibial component; both of these patients were symptomatic. Variables such as the patient's age, sex, diagnosis, alignment and position of the prosthesis, and level of bone cut did not correlate with the development of radiolucencies at the cement-bone interface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335109 TI - Revision total knee arthroplasty for aseptic failure. AB - Twenty-four patients with 28 failed total knee arthroplasties replaced with porous-coated anatomic (PCA) primary or revision components were studied over a two- to four-year period. Overall, there were 68% good and excellent results and three failures. When evaluated according to mode of failure, 83% of the patients who had a definable mechanical problem achieved good or excellent results. Patients who had revision operations for incapacitating pain or in whom no clearly definable problem could be ascertained before operation were not significantly improved. Complications that led to poor results were deep sepsis, wound necrosis, and extensor mechanism abnormalities. PMID- 3335110 TI - The results of revision total knee arthroplasty. AB - The results of 65 consecutive revision total knee arthroplasties performed for mechanical failure were reviewed. Fifty-nine of the knees were followed for an average of five years (range, 2-10 years). The types of implants used included: total condylar, posterior stabilized, total condylar III, and the kinematic rotating hinge prostheses. Only 46% of the knees were considered excellent or good; 42% either had poor results or failed. The infection rate was 4.5%. Poor results were generally caused by patellofemoral problems and kinematic abnormalities. Revision total knee arthroplasty is a technically demanding procedure that can improve function when anatomic relationships of the knee are restored. PMID- 3335111 TI - Intracranial hemorrhage in term or near-term newborns with persistent pulmonary hypertension. AB - To substantiate the clinical impression of an increased incidence of intracranial hemorrhage (ICH) in term and near-term infants with persistent pulmonary hypertension (PPH), a retrospective chart review of 35 affected patients was performed. ICH was diagnosed in 40 percent of the patients. Multiple regions of the brain were affected; in many patients, at more than one location. In addition, 43 percent of ICH victims had hemorrhages of the type associated with periventricular bleeding in preterm newborns. Of multiple obstetric and neonatal factors analyzed, many of which are identified risk factors for periventricular hemorrhage, only thrombocytopenia (p = 0.02) was significantly associated with ICH. We conclude that the risk of ICH in newborns with PPH is significant and warrants consideration by clinicians caring for this population. Risk factors (except thrombocytopenia) previously implicated in other types of neonatal ICH, particularly periventricular hemorrhage, do not significantly correlate with ICH in infants with PPH. PMID- 3335113 TI - Interpretation of traumatic lumbar puncture. PMID- 3335112 TI - Multiple sclerosis presenting at 4 years of age: clinical and MRI correlations. AB - The authors present a patient with multiple sclerosis (MS) whose onset of illness was at 4 years of age. Three separate and distinct episodes of central nervous system (CNS) dysfunction associated with cerebrospinal fluid (CSF) pleocytosis, electroencephalographic (EEG) abnormalities, and extensive CNS white matter demyelination on both computerized tomography (CT) and magnetic resonance imaging (MRI) characterized her clinical course. Two episodes responded well to prednisone therapy. PMID- 3335114 TI - Severe cardiomyopathy simulating hepatitis in adolescence. PMID- 3335115 TI - Neurologic aspects of bronchopulmonary dysplasia. AB - Thirty seven infants were identified with bronchopulmonary dysplasia (BPD). Their hospital records were examined and survivors evaluated to determine the neurologic aspects of BPD. Five infants exhibited progressive neurologic disease; nine infants, Five infants exhibited progressive neurologic disease; nine infants, nonprogressive neurologic disease; and 19, normal neurologic outcome. In four, neurologic outcome was indeterminate because of early death. Thus, evaluation of this population of infants with BPD has established two syndromes of neurologic disease--progressive and nonprogressive. The patients with nonprogressive neurologic disease exhibited static neurologic deficits identical to those described in earlier reports of outcome in infants with BPD. The infants with apparently progressive neurologic disease had clinical courses comparable to the fatal pattern of cerebral deterioration previously described. The syndromes appear to be distinct in etiology and clinical presentation. Intraventricular hemorrhage complicated by hemorrhagic intracerebral involvement appears the factor most clearly associated with nonprogressive neurologic disease. The etiology of the striking progressive neurologic syndrome could not be so clearly established but appears to be related to the course and treatment of BPD. PMID- 3335116 TI - Does your institutional review board review advertising for recruits? PMID- 3335118 TI - Certifying physicians in clinical pharmacology. PMID- 3335117 TI - Plasma concentration-response relationships for some cardiovascular effects of dihydropyridines in healthy subjects. AB - The pharmacokinetics and some hemodynamic effects of three dihydropyridine (DHP) calcium channel blockers were studied in healthy subjects. In a randomized order, each subject was given 24 micrograms/kg nifedipine, 40 micrograms/kg nitrendipine, or 10 micrograms/kg nisoldipine intravenously. The three DHPs differed as to their total clearance and volume of distribution (nifedipine less than nisoldipine less than nitrendipine) but showed similar values for elimination half-lives. All three drugs evoked increases in heart rate and forearm blood flow (FBF) and small decreases in blood pressure. Whereas the observed peak changes in heart rate were virtually identical for the three drugs (about 45% above baseline), the peak changes in FBF were more pronounced in response to nitrendipine and nisoldipine (greater than 200% above baseline) than in response to nifedipine (79% above baseline). The heart rate and FBF responses to the DHPs were related directly to the drug concentrations in plasma. The plasma level-response curves obeyed Hill's equation. They showed that the DHPs differ mainly in their potencies at dilating the forearm resistance vessels (nifedipine less than nitrendipine less than nisoldipine). PMID- 3335119 TI - Chronic effects of nitrendipine on renal hemodynamics and tubular transport. AB - The effects of nitrendipine (10 mg, during acute clearance experiments) given both acutely and after 2 weeks of administration were examined in normal and hypertensive subjects. At the initiation of therapy, nitrendipine caused an increase in glomerular filtration rate and effective renal plasma flow in the hypertensive, but not in the normal, group. Percentage excretion rates of sodium (%ENa) and phosphate (%EPi) and free water clearance (CW) increased in both groups at the initiation of therapy. After 2 weeks of nitrendipine therapy repeat acute clearance studies showed that the drug no longer increased glomerular filtration rate or effective renal plasma flow in hypertensive subjects, the increases in %ENa and CW persisted in normal subjects and trended upward in hypertensive subjects, and the increase in %EPi persisted in both normal and hypertensive individuals. We conclude that nitrendipine is not sodium retentive after chronic therapy and the acute increase in %ENa, %EPi, and CW after its initial administration suggests a proximal tubular effect. PMID- 3335120 TI - Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease. AB - The pharmacokinetics and pharmacodynamics of codeine and its metabolites codeine glucuronide, morphine, and morphine glucuronide were assessed after the administration of a single 60 mg oral dose of codeine sulfate and a single 60 mg intravenous dose of codeine phosphate in six healthy volunteers and six patients on chronic hemodialysis. Plasma and urine drug and metabolite concentrations were determined by sensitive and specific RIA procedures. Pharmacodynamics were assessed by pupillometry and vital sign determinations. Codeine elimination half life and mean residence time were increased significantly in the hemodialysis group (18.69 +/- 9.03 hours and 12.77 +/- 7.09 hours, mean +/- SD, respectively) compared with the healthy volunteer group (4.04 +/- 0.60 hours and 3.90 +/- 0.52 hours, respectively). The total body clearance and volume of distribution of codeine were not significantly different between groups. Peak concentrations, times to peak concentrations, and AUCs for the three metabolites were also not significantly different between the groups, in part as a result of significant interpatient variability in the hemodialysis group. Examination of pupillometry and vital sign data did not reveal clinically significant differences in pharmacodynamics between the groups. Adjustment of dosage regimen may be required in some patients with uremia receiving multiple-dose codeine therapy. PMID- 3335122 TI - The P-300 event-related potential in experimental nitrous oxide exposure. AB - Without the availability of objective measures of central neurologic dysfunction, neuroepidemiologic investigations of individuals exposed to psychoactive drugs and potential environmental and occupational neurotoxins are extraordinarily difficult, particularly when the central nervous system manifestations are subtle, diffuse, and limited to cognitive deficits. In an attempt to assess and quantitate psychomotor dysfunction, P-300 event-related potentials, Symbol Digit Test, Continuous Performance Test, and Finger Tapping Test were obtained from six subjects sequentially exposed to nitrous oxide at 0%, 10%, 20%, and 40%. With increasing concentration of N2O, there was prolongation of P-300 latency and worsening of Continuous Performance Test and Symbol Digit Test performance; P-300 amplitude and Finger Tapping Test performance were decreased by exposure to N2O. This study demonstrates a dose-dependent reduction in P-300 amplitude and prolongation of P-300 latency in subjects in whom psychomotor impairment was induced by the acute administration of N2O. PMID- 3335121 TI - Naproxen kinetics and disease activity in rheumatoid arthritis: a within-patient study. AB - The effects of rheumatoid arthritis disease activity on the pharmacokinetics of the highly albumin-bound nonsteroidal anti-inflammatory drug naproxen were studied in six patients during chronic therapy. In the same patients, kinetics during active disease were compared with those in improvement. Active disease is commonly associated with hypoalbuminemia: 30 +/- 4 gm/L vs. 41 +/- 2 gm/L (mean +/- SD) at the time of improvement. Total naproxen concentrations were significantly lower in active disease, together with a larger apparent volume of distribution (10.6 +/- 1.8 L vs. 8.4 +/- 1.3 L; P less than 0.05) and total body clearance (0.79 +/- 1.8 L/hr vs. 0.59 +/- 0.14 L/hr; P less than 0.001). Peak unbound naproxen concentrations were 29% +/- 19% (P less than 0.05) lower at the time of improvement. The unbound clearance was found diminished during active disease (390 +/- 277 L/hr) in comparison with improvement (488 +/- 343 L/hr; P less than 0.05). Clinical implications of the alterations in naproxen kinetics induced by polyarticular inflammation in patients with rheumatoid arthritis are discussed. PMID- 3335123 TI - Parameter extraction from heart rate and arterial blood pressure variability signals in dogs for the validation of a physiological model. AB - The paper describes an automatic procedure for improving the extraction of parameters in heart rate (HR) and arterial blood pressure (ABP) beat-to-beat variability signals. Auto- and cross-spectral analysis of such signals is carried out through parametric models and the distribution of the power of the spectra and the phase relationships are compared in various physiological situations induced in the dogs via drug infusion or surgical interventions which do influence the control mechanisms of HR and ABP. This "black-box" approach allows the obtention, directly from the processing of the above-mentioned signals, of the estimation of parameters relative to cardiovascular models, as the ones described by simple equations (Windkessel and Starling laws are introduced as examples). These parameters seem to validate significantly the capability of such models to describe the physiological interactions existing between the two considered signals. Applications may be foreseen both for research and clinical purposes. PMID- 3335124 TI - An on-line microcomputer program for the monitoring of physiological variables during rest and exercise. AB - This paper describes a microcomputer system for the on-line display of physiological variables such as: lung ventilation, tidal volume, respiratory frequency, oxygen consumption, heart rate, oxygen pulse, respiratory exchange ratio, grams of fat and carbohydrate metabolised, mean skin temperature, rectal temperature and mean body temperature. The program has been written in Pascal. The modular nature of this language facilitates modification of the program to make it compatible with a variety of hardware and peripherals. PMID- 3335125 TI - A computer program to calculate mean skin temperature from measurements available from field trials. AB - Attempts to estimate mean skin temperature for subjects during prolonged experiments in field conditions are often made difficult because probes become disconnected or cease to function. There are several equations which allow estimation of mean skin temperature from a reduced number of functioning probes. The Fortran program described chooses the appropriate equation, calculates the mean skin temperature using whichever readings are available from the six selected sites and calculates mean body temperature using also rectal temperature. The organization of the program is such that it could easily be modified for use on results from a wide range of experimental conditions. PMID- 3335126 TI - Drug interactions in a clinic using COSTAR. AB - In a study involving 1499 patients in a family office, prescription data obtained from a computerized record system (COSTAR) were analyzed to determine the drug interaction rate. While prior studies have adequately determined that drug interactions occur frequently in most medical offices this paper presents a methodology for performing such analyses in a very short period of time. By using a computer at all stages, the analysis was computed in less than four weeks and with more accuracy than would otherwise be possible. In addition to the demonstration of a method, the results of our analysis are also of interest. Overall 138 (9.2%) of the study patients were prescribed drugs with known interaction potential and among this group, 123 (72%) had interactions considered to be of "moderate" clinical significance and 36 (17%) had interactions considered to be of "major" significance. PMID- 3335127 TI - Stepwise multivariate discriminant analysis (SMDA) for paired and unpaired biomedical data using microcomputers. AB - It may be necessary in biostatistics to discriminate between individuals and groups. The discriminant analysis is used for this purpose. The discriminant procedure has been programmed for microcomputers. The program has been written in a generic BASIC in order to make the procedure user-friendly. To have such a software package implemented on a personal computer may greatly facilitate the use of this complex analysis in biomedicine. PMID- 3335129 TI - Classification of the main macroscopic lesions produced by larvae of Gasterophilus spp. (Diptera:Gasterophilidae) in free-ranging horses in Umbria. AB - Listed and described herein are the main macroscopic lesions produced along the whole digestive tract of free-ranging horses by larvae of the five Gasterophilus spp., occurring in Umbria, a region of central Italy: Gasterophilus intestinalis, Gasterophilus nasalis, Gasterophilus pecorum, Gasterophilus inermis, Gasterophilus haemorrhoidalis. Lesions are classified on the basis of their sizes and shapes and the host's anatomic sites infested, and they are examined in relation to the developmental stages of larvae causing them. The examination of the lesions shows that it is very difficult to differentiate the hemorrhagic impressions caused by migrating 1st and 2nd instar larvae of all the species in the absence of the specific parasite. It is also difficult to differentiate between the gastric lesions caused by Gasterophilus intestinalis and Gasterophilus pecorum. It has been found that an easy identification is possible even in the absence of parasites for gum lesions and for lesions on the soft palate produced respectively by Gasterophilus intestinalis and Gasterophilus pecorum, for duodenal lesions caused by Gasterophilus nasalis, for rectal lesions caused by Gasterophilus inermis and for duodenal and rectal lesions produced by Gasterophilus haemorrhoidalis. PMID- 3335128 TI - The relationships among palpator experience, milk progesterone concentration and estrus and fertility in cows with palpable corpora lutea treated with cloprostenol. AB - Two hundred and fifty-one cows fresh at least 37 days with normal reproductive tracts and palpable ovarian structures which clinicians believed to be corpora lutea and which were presumed to be producing progesterone were treated with 500 micrograms of cloprostenol. The cows were stratified into three groups based on milk progesterone concentrations in whole milk samples taken at the time of examination. The low group had milk progesterone concentrations less than or equal to 1 ng/ml, the intermediate group had milk progesterone concentrations between 1 and 3 ng/ml, and the high group had milk progesterone concentrations greater than or equal to 3 ng/ml. The proportion of cows in each group inseminated within 5 days of treatment and the fertility at that breeding were compared. There were no significant differences among the groups with respect to the proportion of cows that came into estrus within 5 days. However, the conception rate of the high group (54%) was significantly greater than that of the intermediate group (26%). To study the relationship between practitioner experience and diagnostic accuracy the proportion of cows with low, intermediate and high concentrations of progesterone selected by clinicians with more than 3 years experience was compared to that for clinicians with 3 years of experience or less. Less experienced clinicians were significantly more likely to make a false positive diagnosis of functional luteal tissue in cows with palpable ovarian structures than were more experienced clinicians. PMID- 3335130 TI - Nutritional management of horses competing in 160 km races. AB - A survey was taken of dietary management and training schedules of 54 horses competing in two 160 km endurance races. A total of 52 owners, representing 54 horses, responded to a questionnaire distributed prior to the races. Diet and training schedules were compared between horses that successfully completed the races and those that were eliminated for metabolic reasons. Horses that completed the races were 11.5 +/- 4 years old, weighed 429 +/- 4.5 kg and were ridden 61 +/ 32 km a week when training. Feed intake was reported as "free choice hay or pasture" by 34 of the respondents. Dry matter (DM) hay intake in these horses was estimated to be 3% body weight (kg) minus the kg DM of grain fed, assuming a maximum intake. They were fed 12.3 +/- 2.3 kg feed per day consisting of 10 +/- 2.3 kg hay and 2.3 +/- 1.4 kg of grain. Most had free access to salt and were fed 1 +/- 1 vitamin/mineral supplement per day. Based on Nutritional Research Council (NRC) values for nutrient content of the reported feeds, diets contained 60 +/- 5% total digestible nutrients (TDN), 12 +/- 2% crude protein, 27 +/- 4% crude fiber, 0.72 +/- 0.4% calcium and 0.29 +/- 0.06% phosphorus. Maximum caloric intake was estimated to be 31.9 Mcal per day. Ratios of nutrients fed per kilometer trained were: kg TDN/km = .14 +/- .08, kg crude protein/km trained = .03 +/- .02, and kg crude fiber/km trained = .06 +/- .04.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335131 TI - Transmission of Brucella canis by contact exposure. AB - Transmission studies demonstrated that canine brucellosis can spread from infected to susceptible males maintained in close contact after 4 to 6 months of cohabitation. Spread by males occurred after epididymitis was observed in the infected dogs. Transmission via contaminated urine was suspected, but not proved. The bladder urine of infected males, probably contaminated with seminal fluid, contained higher numbers of B. canis organisms than did that of female dogs. Highest concentrations of bacteria in urine were found between postinfection weeks 8 and 12. Infected females transmitted the infection to contact females after 5 months. Immature females or males infected with B. canis did not transmit brucellosis until after an estrus or a mating was observed--about post-contact months 10-12. PMID- 3335132 TI - The granular layer of Tomes in experimental caries in rats. AB - In examination of ground sections of human third maxillary molar teeth, the granular layer of Tomes was shown to consist of expansion of dentinal tubules. The microradiographic density was decreased well inside the layer. It was postulated that the findings were expressions of dentin resorption. The theory was tested experimentally in rats fed a cariogenic diet with low calcium and phosphorus. The morphology of mandibular molar teeth was studied by electron probe microanalysis and by microradiography. It was concluded that the primary event in cariogenesis was an expansion of peripheral dentinal tubules with formation of confluent microcavities and, thus, an unmasking of the granular layer of Tomes, which normally is only potential. A subsequent loss of mineral density in the outer enamel eventually caused breakdown of the outer enamel with caries visible from the surface. The loss of density within the enamel was postulated to result from interruption of the normal flux of nutrients, metabolites and ions between the dentin and enamel. Whereas an increase in dietary calcium and phosphorus delayed and reduced significantly, but did not prevent cariogenesis, it supported the theory that experimental caries in rats is a metabolic disease with the peripheral dentin the primary target. PMID- 3335133 TI - Repletion of blood selenium concentrations in weaned beef calves. AB - Eighty-three weaned beef calves severely deficient (less than 20 micrograms/L) in blood selenium (Se) were allotted by sex, weight and breed to one of six regimens of Se supplementation for 108 days to examine the efficacy of various Se supplementation programs and to monitor the repletion rate of blood Se concentrations. Cattle in treatment 1 received an IM injection of sodium selenite and an ad libitum feeding of 20 mg Se/kg salt-mineral mixture. Salt-mineral mixtures (treatments 2, 3, 4 and 5) were formulated to contain 20, 40, 80 and 160 mg Se/kg supplement, respectively, and were offered free-choice. Treatment 2 served as the selenium-treated control because 20 mg Se/kg supplement was the maximum permissible by FDA in commercial salt-mineral preparations at the time of this study. Cattle in treatment 6 received a salt-mineral supplement which contained no Se but dried brewers grain (434 micrograms Se/kg) was incorporated in the ration as an organic source of Se and fed at a rate of 1.1 kg/head/day. There was a within group time/treatment interaction (P less than 0.01) among all treatments as blood Se concentrations significantly increased over time. Final mean whole blood Se concentrations for treatments 1-6 were 87.8, 60.6, 95.1, 123.1, 154.2 and 91.4 micrograms/L, respectively. Treatments 1, 3, 4, 5 and 6 effectively increased and maintained whole blood Se concentrations at adequate levels (greater than 70 micrograms/L) by day 84. Treatment 2 (control) increased blood Se during the 108-day study, but blood Se concentrations never exceeded marginal levels (50-70 micrograms/L). Cattle consumed less salt-mineral supplement as the concentration of Na selenite increased from 20 to 160 mg Se/kg supplement. PMID- 3335134 TI - Effects of metoclopramide, clenbuterol and butorphanol on ruminoreticular motility of calves. AB - Rate and amplitude of contractions of the rumen dorsal sac and reticulum of 6 male Holstein calves ages 12 to 20 weeks were monitored with electromyography, strain gauges and an intraruminal pressure catheter. Heart rate and mean arterial pressure were measured with ultrasound. The effects of metoclopramide, a dopamine antagonist, clenbuterol, a beta-2 adrenergic agonist, and butorphanol, a narcotic agonist/antagonist, were observed utilizing dosages bracketing those employed clinically. Metoclopramide significantly decreased the intraruminal pressure peaks associated with cyclical contractions without changing their rate. Clenbuterol had no measurable effect on the ruminoreticulum. Butorphanol totally inhibited ruminoreticular contractions for periods of 6 to greater than 40 min depending on dosage. Only clenbuterol significantly affected cardiovascular function; it increased heart rate and decreased mean arterial pressure. Both metoclopramide and butorphanol produced behavioral changes in the calves. PMID- 3335135 TI - Biliary bilirubin and biliverdin excretion in rabbits during fasting and feeding. AB - Biliary excretion rate of bilirubin and biliverdin from fasted and fed conscious rabbits has been investigated. The animals were cholecystectomized and fitted with a chronic surgical double recurrent choledoco-choledocal biliary fistula. The enterohepatic circulation of bile salts were maintained by bile administration. Mean bile flow, biliary concentrations and excretion rates of bilirubin and biliverdin remained constant during fasting conditions. After feeding bile flow and biliary output of biliverdin increased whereas that of bilirubin did not. The higher excretion rate of biliverdin after feeding could be explained by the low biliverdin reductase activity in this species and the stimulation of biliverdin formation by postprandial factors. PMID- 3335136 TI - A continuing commitment to critical care. PMID- 3335137 TI - Community-acquired pneumonia. Back to basics. PMID- 3335138 TI - Women and the obstructive sleep apnea syndrome. AB - Twenty-seven women referred to a sleep disorders clinic for symptoms of obstructive sleep apnea syndrome (OSAS) during one year were systematically analyzed after polygraphic monitoring of sleep and cephalometric x-ray examination. Our subjects, one-third of whom were premenopausal, comprised approximately 12 percent of the total OSAS population seen. Women with OSAS were compared with 110 OSAS men and with a group of 16 women without OSAS but referred to orthodontists for mild dental malocclusion. Women with OSAS were massively obese, much more so than their male counterparts. There was no significant difference between pre- and postmenopausal women, with the exception of the respiratory disturbance index (RDI), which was lower in the postmenopausal group despite similar morbid obesity (seemingly better tolerated by women with OSAS than by men with the same syndrome) and long mandibular plane-hyoid bone distance. The significantly higher RDI noted in premenopausal women, despite equally massive obesity and upper airway abnormalities, is thought to be related to hormonal status and better arousal response. Chronic obstructive lung disease (COLD) seen in a subgroup of women with OSAS did not differentiate this subgroup from the other OSAS patients when oxygen saturation during sleep, frequency of abnormal respiratory events and sleep variables were considered. Massive obesity is the dominant factor for the appearance of OSAS in women. PMID- 3335140 TI - Poor prognosis in patients with rheumatoid arthritis hospitalized for interstitial lung fibrosis. AB - Fifty-seven patients with rheumatoid arthritis (RA) were treated in hospital for diffuse interstitial lung fibrosis. Although interstitial fibrosis (either on the basis of lung function tests or chest roentgenograms or both) is fairly common among patients with RA, according to this study interstitial fibrosis of sufficient extent or severity to warrant hospitalization was rare: incidence of hospitalization due to the lung disease in RA patients was one case per 3,500 patient-years. Eight patients had a largely reversible lung disease associated with drug treatment (gold, D-penicillamine or nitrofurantoin.) The remaining 49 had interstitial fibrosis of unknown cause. Causes for hospitalization were respiratory and general symptoms in 38, but infiltrations on routine chest roentgenographic examinations alone in eleven patients. Forty-five out of the 49 patients had crackles on auscultation. The most typical findings in lung function tests were restriction and a decreased diffusion capacity. These 49 patients showed a poor prognosis, with a median survival of 3.5 years and a five-year survival rate of 39 percent. PMID- 3335139 TI - Plasma cells in the bronchoalveolar lavage fluid of a patient with eosinophilic pneumonia. Morphologic proof of local production of antibodies. AB - We describe a case of eosinophilic pneumonia in which plasma cells appeared in bronchoalveolar lavage fluid (BALF). A 49-year-old man presented with wheezing, lung infiltrates, peripheral eosinophilia, and extremely high IgE levels in serum and BALF. A differential count of BALF revealed 56.6 percent lymphocytes and 1.3 percent plasma cells. The appearance of plasma cells suggests local maturation of B cells and represents a morphologic proof of local production of immunoglobulins. The increased number of lymphocytes suggests their role in B cell differentiation via the lymphokine network. PMID- 3335142 TI - Fifteen-year interval spirometric evaluation of the Oregon predictive equations. AB - The 1969 Oregon spirometric predictive equations were evaluated by retesting 199 of the 988 original sample population after 15 years. The 1969 data were used to test for sample bias between the retested and not-retested groups. There was no significant difference in mean values for age, height, or test results except for a five-year age difference in men. Regression analysis of residuals and the differences between calculated and predicted values of annual decrements of FVC, FEV1, and FEF25-75% on age revealed no statistically significant age trend. Although residual means were statistically significant for FVC and FEV1 for men and FVC and FEF25-75% for women, the differences between calculated and predicted annual decrements were significant only for women in FEF25-75%. Although group performance was accurately predicted for most tests, test SDs and SEMs demonstrated considerable individual variation. Lower limits of normality are suggested to assist in evaluating previously-tested patients. PMID- 3335141 TI - Cor pulmonale due to adenoidal or tonsillar hypertrophy or both in children. Noninvasive diagnosis and follow-up. AB - Four children, aged 1 to 3 1/2, were first seen with cor pulmonale, pulmonary edema and severe respiratory distress due to chronic upper airway obstruction secondary to adenoidal or tonsillar hypertrophy or both. Arterial blood gas values, electrocardiograms and chest x-ray films were compatible with cor pulmonale. Echocardiography (four cases) and radionuclide angiography (two cases) showed severe right ventricular and right atrial dilation with reduced right ventricular ejection fraction. Following surgery, all four children improved; their echocardiographic and radionuclide findings returned to normal. Cardiac catheterization, traditionally performed in such cases, was unnecessary. The diagnosis and follow-up of this syndrome are adequately performed noninvasively. PMID- 3335143 TI - Estimates of ventilation from inductance plethysmography in sleeping asthmatic patients. AB - To assess the accuracy of the respiratory inductance plethysmograph (RIP) for monitoring ventilation during sleep-associated bronchoconstriction, five adult patients with nocturnal worsening of their asthma were monitored overnight in the sleep laboratory. Three of the five patients demonstrated episodic paradoxic respiratory motion of the lower rib cage undetected by the RIP. Such paradoxic motion was consistently associated with overestimation of volumetric data by RIP compared to pneumotachygraphic measurements. With onset of lower rib cage paradox, the mean error of RIP-derived VT measurements increased from 9.1 +/- 1.7 to 27.9 +/- 3.8 percent (p less than .001). Flow measurements derived from RIP were also inaccurate in the presence of lower rib cage paradox, with the mean error of the measurement increasing from 9.0 +/- 2.5 to 33.5 +/- 5.3 percent (p less than .001). We conclude that RIP is an unreliable technique for quantitatively monitoring ventilation in sleeping asthmatic patients. PMID- 3335144 TI - Respiratory illness in the construction industry. Airflow obstruction among painters. AB - To assess the potential respiratory effects of exposure to paint products, the pulmonary function of 118 construction painters was compared to construction workers unexposed to paints (314 sheet metal workers). When compared to sheet metal workers, painters reported significant excess symptoms of cough (p less than 0.05), wheezing (p less than 0.001), and dyspnea (p less than 0.0001). Nonsmoking painters working at least 15 years in the trade had significant decrements in percent predicted forced expiratory volume in one second (%FEV1)(p less than 0.025) and in the percent predicted ratio of the forced expiratory volume in one second to the forced vital capacity (%FVC1/FVC) (p less than 0.025). Current smoking painters working less than 15 years in the trade demonstrated significant decrements in %FEV1 (p less than 0.05) and %FEV1/FVC (p less than 0.05). Restricting the analysis to painters, and controlling for smoking, we observed a significant relationship between years of exposure to paint products and airflow obstruction. Painters may be at risk for developing airflow obstruction and these changes appear to be related to the duration of exposure to paint products. Painters who smoke may be at risk of developing this obstructive process earlier than nonsmokers. PMID- 3335146 TI - Surface morphology of the human pleura. A scanning electron microscopic study. AB - The superficial morphology of the pleura has been observed in humans by scanning electron microscopy (SEM). Pleural samples from the visceral, mediastinal, diaphragmatic and costal normal human pleura were observed, and a thorough morphometric study was performed. The most evident feature was the ubiquitous presence of microvilli and micropores. The secretion and absorption activities therefore should not be regarded as accomplished by different topographic zones of the pleura. Discontinuities and clefts were observed at the level of cellular junctions; absorption of high weight molecules and cells from the pleural space may be facilitated at this level, but the structures which were observed in humans may not be considered "stomata," according to the definition of such morphologic units as we give in the present study. Cilia and blebs, described in the experimental animal or in other mesothelia, were not seen in the human pleura. PMID- 3335145 TI - Cardiovascular effects of smoking in patients with ischemic heart disease. AB - The cardiovascular effects of smoking, including the occurrence of ventricular arrhythmias, were examined in 52 patients with ischemic heart disease. The study was a randomized, crossover comparison between smoking six cigarettes and nonsmoking with observer-blinded primary outcome measurements. Continuous Holter ECG recording for four hours showed no significant differences in the proportion of patients experiencing ventricular ectopy or the total number and complexity of ventricular premature beats during smoking vs nonsmoking. Aside from the first cigarette, smoking did not significantly alter blood pressure or heart rate. Mean (+/- SEM) plasma epinephrine (pg/ml) increased (p = 0.02) from baseline (52 +/- 4) to a maximum of 64 +/- 6 at 240 minutes with younger subjects exhibiting a more marked rise (p = 0.02) than subjects over 55 years of age. Plasma norepinephrine was unchanged by smoking. A power calculation confirmed the conclusion that the resumption of smoking after overnight abstention does not acutely increase the occurrence of ventricular ectopic activity in patients with ischemic heart disease. PMID- 3335147 TI - Eosinophilia, respiratory symptoms and pulmonary infiltrates in rubber workers. AB - This report describes a spectrum of respiratory illnesses associated with eosinophilia which occurred in a group of workers exposed to fumes from a synthetic rubber-based curing operation. Respiratory syndromes induced by this exposure included an acute sensitizing illness with dyspnea and wheezing in some workers and pulmonary infiltrates with eosinophilia in others. Another worker developed chronic obstruction of the airways with recurrent bronchitic illnesses. Mild to marked peripheral eosinophilia, up to 3,000/cu mm, was usually present in the symptomatic workers and in 11 of 30 asymptomatic workers. These cases illustrate the diversity of respiratory illnesses which may result from a common workplace exposure and reinforce the importance of considering occupational exposures in the differential diagnosis of peripheral eosinophilia. PMID- 3335149 TI - Critical care practices of chest physicians. PMID- 3335148 TI - Prognostic factors in diffuse malignant pleural mesothelioma. A study of 167 patients. AB - The existence of large shipyards accounts for the particular frequency of pleural mesothelioma in the Nantes-St. Nazaire region of France. From 1955 to 1985, 167 cases were diagnosed. Occupational exposure to asbestos was involved in 131 cases (88 percent). There was a great predominance of epithelial types (135) over mixed (25) and fibrosarcomatous (7) types. Survival, estimated by the actuarial method, was 54 percent at one year from first symptoms and 39 percent from histologic diagnosis. No subject was alive four years after diagnosis. Histologic type and asbestos exposure had no predictive value in our series. Survival was longer in patients under 60 years of age and when mesothelioma originated on the left side. Overall, treated patients had significantly longer survival than untreated patients. However, there was no significant difference in survival with respect to the type of treatment given: surgery, chemotherapy, talc poudrage or their combination. PMID- 3335150 TI - Effect of dobutamine on lung microvascular fluid flux in sheep with "sepsis syndrome". AB - The effect on pulmonary fluid balance of adrenergic receptor agonist agents commonly employed in clinical sepsis has not been well characterized. Therefore, we tested the hypothesis that dobutamine would increase pulmonary microvasular fluid flux in experimental sepsis-induced lung injury. To define the effects of this synthetic catecholamine on pulmonary lymph flow (QL), we infused dobutamine in sheep at two doses in sequence (5 micrograms/kg/min and 10 micrograms/kg/min) before and after the induction of intraperitoneal sepsis which resulted in the development of lung microvascular injury. In the nonseptic state, cardiac output increased at both 5 micrograms/kg/min and 10 micrograms/kg/min (22 and 36 percent, respectively), while QL was unchanged from baseline (for 5 micrograms, delta QL = +0.44 +/- 1.35 ml/15 min; not significant) (for 10 micrograms, delta QL = -0.20 +/- 1.0 ml/15 min; not significant). Values for the ratio of lymph/plasma total protein levels [( L/P]TP) fell modestly in the nonseptic study at both doses (p less than 0.05). With established sepsis syndrome, QL increased from the nonseptic baseline study (2.99 +/- 1.8 to 7.01 +/- 3.95 ml/15 min; p less than 0.05), without change in [L/P]TP ratios or the calculated microvascular hydrostatic pressure. (Pmv) During sepsis, dobutamine infusion was again associated with an increase in cardiac output at both the 5 micrograms/kg/min (+29 percent) and 10 micrograms/kg/min (+33 percent) doses, while QL increased modestly only with the lower dose of dobutamine infused (5 micrograms/kg/min, delta QL = 1.80 +/- 2.2 ml/15 min; p less than 0.05). In this model of sepsis induced lung injury, dobutamine increased systemic flow without substantially augmenting QL. PMID- 3335152 TI - Diagnostic imaging of intralobar bronchopulmonary sequestration. PMID- 3335151 TI - Intracavitary mass in a patient with Klebsiella pneumonia. PMID- 3335153 TI - Diltiazem and exercise performance in patients with chronic atrial fibrillation. AB - To evaluate the influence of calcium entry blockade (diltiazem 60 mg qid) on exercise capacity in patients with chronic atrial fibrillation, nine men (mean age 65 years) with atrial fibrillation underwent maximal treadmill exercise on and off diltiazem therapy. Heart rate, blood pressure, and measured ventilatory parameters were assessed at a standard submaximal workload (3.0 mph/0% grade), the gas exchange anaerobic threshold (ATge), and maximal exercise. Significant reductions in heart rate at all stages of exercise were demonstrated: maximum heart rate decreased from 171 +/- 30 beats/min to 142 +/- 27 beats/min (17 percent, p less than .01) and submaximal exercise heart rate decreased from 123 +/- 22 beats/min to 96 +/- 16 beats/min (22 percent, p less than .01). However, there were no significant changes in blood pressure or gas exchange data, ie, oxygen uptake, minute ventilation, or respiratory exchange ratio at any of the exercise workloads. These data demonstrate that in patients with chronic atrial fibrillation, diltiazem controls the ventricular rate response throughout exercise without attenuating blood pressure or exercise capacity. PMID- 3335154 TI - Lymphocytic bronchiolitis associated with HIV infection. AB - Patients with the acquired immune deficiency syndrome (AIDS) frequently develop interstitial lung disease. This is due most commonly to opportunistic infections, but malignancy and lymphocytic interstitial pneumonitis have also been associated with the syndrome. In contrast, there has been little reported about airways disease in patients with HIV infection. We describe a patient with AIDS-related complex who presented with symptoms and radiographic evidence of micronodular interstitial lung disease. Transbronchial biopsy revealed a lymphocytic bronchiolitis but no evidence of interstitial lung disease and a marked T suppressor lymphocytosis was found on analysis of the bronchoalveolar lavage (BAL) specimen. Routine fungal, viral and bacterial cultures did not yield an etiologic agent. This case raises the possibility that lymphocytic bronchiolitis may represent another pulmonary manifestation of HIV infection. PMID- 3335155 TI - Anomalous origin of the left main coronary artery from the right sinus of Valsalva with coronary AV fistula of the conus artery. AB - A 44-year-old man with atypical chest pain, anomalous origin of the left main coronary artery from the right sinus of Valsalva with coronary AV fistula of the conus artery is presented. I am aware of no other report of this combination of anomalies. PMID- 3335157 TI - Pulmonary vein and superior vena cava obstruction due to expanding aneurysm of the pulmonary artery. AB - A patient with tricuspid atresia, Potts' anastomosis, and longstanding pulmonary hypertension expired following expansion of an aneurysm of the pulmonary artery trunk. The aneurysm compressed the atria, obstructing an obligatory atrial septal defect, the superior vena cava and the right pulmonary veins, causing pulmonary edema, massive pleural effusion and superior vena cava syndrome. PMID- 3335156 TI - Coronary spasm complicating sclerotherapy of esophageal varices. AB - There are rare serious cardiac complications associated with endoscopic examination. An episode of coronary artery spasm developed in a 68-year-old man during endoscopic sclerotherapy for esophageal varices. The coronary artery spasm may have been triggered by a reflex increase in sympathetic discharge under stressful circumstances, and may occur most often in patients with preexisting heart disease. In patients with severe cardiac disease, ECG monitoring during the procedure seems justified. PMID- 3335159 TI - Increased mitral valve insufficiency during precordial "whoop". AB - A patient with rheumatic mitral valve stenosis and regurgitation presented with shortness of breath and a "noise" in her chest. Cardiac auscultation revealed an intermittent late systolic "whoop." An increase in severity of mitral valve insufficiency during the periods of "whoop" was observed by pulsed Doppler, hemodynamic tracings and left ventriculography. PMID- 3335160 TI - Gas flow through a bronchopleural fistula. Measuring the effects of high frequency jet ventilation and chest-tube suction. AB - High-frequency jet ventilation (HFJV) is FDA-approved for ventilating patients with bronchopleural fistulae (BPF), yet little is known about its effect on the fistula airleak. We quantitated a patient's BPF airleak during both conventional volume-cycled ventilation and HFJV. The effect of chest-tube suction (CTS) on BPF flow was also studied. Despite a significant reduction in peak airway pressure, the HFJV resulted in a 50-70 percent increase in BPF flow. CTS also significantly increased the airleak. HFJV may not always be the preferential method for ventilating patients with BPF and we recommend measuring the fistula airleak when attempting to optimize a patient's ventilatory parameters. PMID- 3335158 TI - Sarcoma of the pulmonary artery. AB - A patient is described in whom clinical presentation, V/Q scan, and pulmonary angiogram were consistent with pulmonary embolus. No improvement occurred despite therapy with heparin. When sent for surgical embolectomy, sarcoma of the pulmonary artery was diagnosed. This entity, though rare, should be considered in the differential diagnosis of pulmonary vascular disease. PMID- 3335161 TI - Desquamative interstitial pneumonia. Computed tomographic findings before and after treatment with corticosteroids. AB - Noninvasive methods for diagnosis, assessing prognosis, and following response to treatment in idiopathic pulmonary fibrosis (IPF) have yet to prove their usefulness. We report a patient with desquamative interstitial pneumonia (DIP) in whom computed tomography (CT) suggested the diagnosis by the presence of patchy areas of haziness predominantly in a peripheral distribution. The chest x-ray and physical examinations, and the arterial blood gases showed normal findings after one month of treatment with corticosteroids, at which time the CT scan and lung volumes were still abnormal. At three months, lung volumes and the CT scan were normal. Hazy densities in a peripheral distribution on CT may indicate active IPF associated with a good prognosis. PMID- 3335162 TI - Lysozyme in pleural effusions. PMID- 3335163 TI - Charcot-Marie-Tooth disease and respiratory failure. PMID- 3335164 TI - Diagnostic value of nonbronchoscopic bronchoalveolar lavage during mechanical ventilation. PMID- 3335165 TI - Aspiration of an artificial nasopharyngeal airway. PMID- 3335166 TI - Effect of routine administration of analgesia on energy expenditure in critically ill patients. AB - Measurement of gas exchange using portable metabolic carts to indirectly determine energy expenditure (EE) has been a recent advance in the nutritional management of mechanically ventilated, critically ill patients. Although administration of large doses of morphine has been shown to significantly decrease EE, the influence on EE of morphine given in routine amounts to critically ill patients has not been studied previously. We examined the effect of morphine administration (given as bolus IV injections of 0.10 mg/kg every two hours and continuous IV infusion at 0.05 mg/kg/hr) on EE during rest and various ICU activities in seven mechanically ventilated patients. Morphine administration resulted in a significant reduction in resting EE and total EE of 6.0 and 8.6 percent, respectively. However, EE associated with activities (ie, chest x-ray examination and chest physiotherapy) were not significantly affected by morphine administration. Both bolus and continuous IV morphine infusion had similar effects on EE. Administration of routine doses of morphine significantly decreases total EE in critically ill patients. This should be considered an important factor influencing measurements of EE. PMID- 3335167 TI - Reversibility of airway obstruction in relation to prognosis in chronic obstructive pulmonary disease. AB - Whether reversibility in airway obstruction with beta-adrenergic stimulant is a significant determinant for the outcome was tested in 59 patients with pulmonary emphysema and chronic bronchitis. During four years of follow-up, 43 (73 percent) patients survived and 16 (27 percent) died. Initial VC. FVC, FEV1, and PaO2 were significantly smaller, and PaCO2 was significantly larger in nonsurvivors than those in survivors. After orciprenaline sulfate (10 mg in 0.5 ml solution) inhalation, VC and FEV1 increased in comparable amount between the two groups. Airway reversibility as estimated by percentage changes in FEV1 before and after the bronchodilator (reversibility index) was similar between the two groups. In the 16 nonsurvivors, hypoxemic patients had similar FEV1, FEV1/FVC, and reversibility indices as normoxemic patients. These results indicate that not airway reversibility per se but a fixed or irreversible component of airway obstruction is one of the determinants of the prognosis in pulmonary emphysema and chronic bronchitis. Chronic hypoxemia is related to neither airway obstruction nor its reversibility, while it does influence the prognosis. PMID- 3335168 TI - Safety and efficacy of amiodarone. The low-dose perspective. AB - Amiodarone has been reported to be a remarkably safe and effective drug in the European and South American experience but American investigators have published conflicting data. Since this disparity may be explained by a different dosing schedule, we prospectively evaluated the safety and efficacy of a low dose regimen in a group of 68 patients with cardiac arrhythmia resistant to conventional therapy, of whom 57 had manifested either ventricular tachycardia or fibrillation. All were loaded either intravenously (17) or orally, and maintained on an oral dose of 200 to 600 mg/day (mean daily dose 317 +/- 114 mg) and followed for 4 to 58 months (22 +/- 11). Results indicated that amiodarone was a safe and effective antiarrhythmic drug when used in lower doses. PMID- 3335169 TI - Physiologic assessment of lung function in patients undergoing laser photoresection of tracheobronchial tumors. AB - We performed YAG laser photoresection in 11 patients with tracheal or mainstem bronchial obstruction due to malignant or benign disorders. We used maximal inspiratory-expiratory flow-volume loops and expiratory volume-time plots to assess air flow limitation. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) and iso-volume maximal flows at 50 percent of forced inspiratory and expiratory volume were calculated. Spirograms and flow-volume loops were repeated within 12 to 72 hours of laser resection. All patients had flattened expiratory limbs on their flow-volume loops. All spirometric parameters increased significantly following laser photoresection. In particular, peak flow improved in all patients, and FEV1 improved in nine of 11 patients, even though four patients had moderate to severe obstructive ventilatory defects which persisted after resection and were probably due to longstanding chronic obstructive pulmonary disease. We conclude that flow volume loops and spirometry are helpful in assessing the site and nature of malignant large airway obstructive processes and, moreover, provide reliable information for evaluating the efficacy of laser photoresection. Serial physiologic studies indicate changes in the caliber of the upper airways and can be used as a simple means of following these patients. PMID- 3335170 TI - Utility of fiberoptic bronchoscopy in patients with hemoptysis and a nonlocalizing chest roentgenogram. AB - The need for fiberoptic bronchoscopy in the patient with hemoptysis and a normal or nonlocalizing chest roentgenogram remains a subject of debate. Currently, diagnostic fiberoptic bronchoscopy is recommended as the investigative procedure of choice. To develop predictors that identify the patient in whom fiberoptic bronchoscopy is most likely to be diagnostic, we reviewed our community's experience with this population over a five-year period. We identified 196 patients with hemoptysis and a normal or nonlocalizing chest roentgenogram who underwent fiberoptic bronchoscopy. Three quarters were active or previous smokers. We examined the relationship of advancing age, sex, smoking, nonspecific roentgenographic findings and the amount, duration, and previous bouts of hemoptysis to the incidence of a diagnostic fiberoptic bronchoscopy. Twelve patients (6 percent) had bronchogenic carcinoma and 33 (17 percent) another specific cause for the hemoptysis identified by fiberoptic bronchoscopy. By univariate and discriminant analyses, we found that the three factors of age of 50 years or more, male sex, and smoking of 40 pack-years or more best predicted a diagnosis of malignancy. Bleeding in excess of 30 ml daily was associated with an increase in overall diagnostic yield. The presence of two of the three factors associated with malignancy or bleeding in excess of 30 ml daily (or both) identified 100 percent of the patients with bronchogenic carcinoma and 82 percent of all of the diagnostic fiberoptic bronchoscopic procedures. use of these criteria in selecting the patient for fiberoptic bronchoscopy could have reduced our use of the bronchoscope by 28 percent, with the remaining patients safely observed. PMID- 3335171 TI - Altitude exposures during aircraft flight. Flying higher. AB - Commercial aircraft flight represents a highly variable altitude exposure that may result in significant hypoxemia for patients with cardiac or pulmonary disease. To develop better guidelines for travel by patients with cardiopulmonary disease, we measured inflight cabin altitude on 204 regularly scheduled commercial aircraft flights. Measurements were carried out on 16 different types of aircraft, operated by 28 airlines. The median altitude exposure for all flights was 6,214 feet (1894 m). Cabin altitudes ranged from sea level to 8,915 feet (2717 m). Inspired partial pressure of oxygen falls from 159 mm Hg at sea level to 127 mm Hg at 6,200 feet and further declines to 113 mm Hg at 9,000 ft. There was no significant difference between domestic and international flights. New generation aircraft fly at higher altitudes than older aircraft and are associated with greater altitude exposures to passengers (p = 0.002). The risk of hypoxemia may increase as newer model aircraft replace older ones. PMID- 3335172 TI - Idiopathic dilated cardiomyopathy. Role of programmed electrical stimulation and Holter monitoring in predicting those at risk of sudden death. AB - The prognostic role of programmed electrical stimulation and Holter monitoring was evaluated in 21 patients with idiopathic dilated cardiomyopathy who had no prior history of ventricular tachyarrhythmias. During a mean follow-up period of 23 months, sudden death or ventricular fibrillation occurred in four (20 percent). One patient died of complications of sepsis, and one underwent cardiac transplantation. Programmed electrical stimulation (PES) resulted in five or more beats of induced ventricular tachycardia in seven patients (33 percent), but was a poor predictor of sudden death (sensitivity = 20 percent). Thirteen patients (62 percent) had complex ventricular ectopy (Lown class 4A or 4B) by ambulatory monitoring. This was a sensitive (80 percent) but not specific (31 percent) marker for sudden death. The predictive value of a negative Holter monitor study was high (80 percent) for identifying those at low risk of sudden death. The results of this prospective study suggest that programmed ventricular stimulation and routine ambulatory monitoring are poor predictors of sudden death in this population. PMID- 3335173 TI - Lung volume standards for healthy male lifetime nonsmokers. AB - Functional residual capacity (FRC), residual volume (RV), vital capacity (VC), and total lung capacity (TLC) were measured in 162 men aged 18.9 to 78.6 years using a multiple breath helium dilution technique. Multiple regression equations were generated to predict these lung parameters from the best weighted combination (p less than or equal to 0.05) of age, mass, standing height, body surface area, sitting height, biacromial breadth, end-tidal chest girth, expanded chest girth, and chest expansion (FRC: R = .748, SEE = 504 ml; RV: R = .725, SEE = 301 ml; VC: R = .808, SEE = 537 ml; TLC: R = .808, SEE = 551 ml; RV/TLC: R = .778, SEE = 4.15 percent). The range of normality was defined as the predicted value +/- the 95 percent confidence interval (two-tailed test). Cross-validation of other FRC, RV, VC, and TLC equations in the literature indicated that they were unsuitable for use with our data. PMID- 3335174 TI - An outbreak of Q fever probably due to contact with a parturient cat. AB - Thirty-three cases (24 definite, nine probable) of Q fever were diagnosed in Victoria County, Cape Breton, Nova Scotia from May to August, 1985. Twenty-six of the cases occurred in residents of Baddeck (population 900, attack rate 2.8 percent), and 21 of the cases occurred during the month of June. There was geographic clustering of the cases: 14 of the 33 (42 percent) lived or worked in four buildings located side by side in the center of town. A case control study revealed that 25 of 29 cases were exposed to a cat that gave birth to stillborn kittens on June 8, 1985 and had bled per vaginum for three weeks prior to delivery. The cat lived in one of the buildings where geographic clustering occurred and frequently visited the other buildings. None of the 40 control subjects was so exposed (p less than 0.001). This cat had an antibody titer of 1:512 to Coxiella burnetii phase 1 antigen and a titer of 1:1024 to phase 2 antigen. Exposure to cattle, sheep and goats, the traditional reservoirs of Q fever, was uncommon among patients and control subjects and none of eight cattle tested had antibodies to C burnetii phase I antigen. We conclude that the infected parturient cat was probably responsible for this outbreak of Q fever affecting 2.8 percent of the population of the town of Baddeck. PMID- 3335175 TI - Inotropic therapy for cardiac failure associated with acute myocardial infarction. PMID- 3335176 TI - Application and interpretation of submaximal exercise testing and ambulatory ECG recordings in patients with acute myocardial infarction. PMID- 3335177 TI - Enzymatic diagnosis of acute myocardial infarction. PMID- 3335178 TI - Radionuclide assessment and diagnosis of acute myocardial infarction. PMID- 3335179 TI - Health insurance restraints under guise of cost containment. PMID- 3335180 TI - Establishing and operating a third-party reimbursed outpatient diabetes care center. PMID- 3335182 TI - Dietary skills and adherence in children with type I diabetes mellitus. PMID- 3335181 TI - Discrepancies between blood glucose and glycosylated hemoglobin in intensively treated diabetic patients. PMID- 3335183 TI - A contract for change in diabetes self-management: case report. PMID- 3335185 TI - A diabetes simulation for health professionals. PMID- 3335184 TI - Length of hospitalization of children with diabetes: effect of a clinical nurse specialist. PMID- 3335186 TI - Diagnosing timewasters. PMID- 3335187 TI - Over-the-counter product use. PMID- 3335188 TI - Promoting diabetes self-management and independence in the visually impaired: a model clinical program. PMID- 3335189 TI - Supporting third-party reimbursement: the legislative approach. PMID- 3335190 TI - Designing a diabetes nutrition education program for a Native American community. PMID- 3335191 TI - Evolution of diabetes education programs. PMID- 3335193 TI - [Regional intra-arterial chemotherapy with Dacarbazine in isolated liver metastases of a malignant melanoma]. AB - A 58-year-old woman underwent regional intra-arterial chemotherapy for hepatic metastases of a malignant melanoma, because at the time no other organ metastasis was demonstrable. Dacarbazine was injected as a bolus on five successive days, four weeks apart, after which there were several days of fever and the urinary melanogen test became positive. At first the patient clearly improved and was again able to walk. But four months after the start of treatment she died in a hepatic coma. PMID- 3335192 TI - [Therapy of pancreatogenic steatorrhea. Comparison of 2 acid-protected enzyme preparations]. AB - In an open, randomised cross-over trial nine patients with severe exocrine pancreatic insufficiency and considerable steatorrhea (greater than 25 g fecal fat excretion daily) received for five days, after a treatment-free period of three days, two new acid-protected enzyme preparations: Kreon, three times six capsules daily, pellets of 1-2 mm diameter; Panzytrat 20.000, three times three capsules daily, microtablets of 2 mm diameter. Both preparations significantly decreased fecal weight and fecal fat excretion. With equivalent lipase dosage there was no difference in effect between the two preparations. PMID- 3335194 TI - [Possibilities in endoscopic joint surgery]. PMID- 3335195 TI - [Liability of the physician in delayed hospitalization. Opinion of the Hamburg County Court 7 November 1986]. PMID- 3335196 TI - [Urticaria vasculitis]. PMID- 3335198 TI - [Heparin-induced thrombopenia]. PMID- 3335197 TI - [Effect of homeopathy--a placebo effect?]. PMID- 3335199 TI - [Side effects of pirenzepine]. PMID- 3335200 TI - Soluble and polymerized tubulin levels in the anterior pituitary lobe of the lactating rat during suckling. AB - A [3H]colchicine-binding assay was employed for estimating the relative amounts of soluble and polymerized tubulin present in an individual anterior pituitary lobe. Colchicine binding to these two tubulin pools was time dependent and dose responsive. Scatchard analysis of the binding revealed that [3H]colchicine bound to both fractions with similar affinity. After establishing the optimal conditions for the binding assay, the effect of suckling on the relative levels of the two tubulin pools was studied. Groups of primiparous rats on days 12-14 postpartum were isolated from their pups for 4-5 h, then suckled for 30, 60, and 90 min, and killed, and the anterior pituitary lobes were dissected out. Each pituitary lobe was processed to obtain the two tubulin pools, viz. soluble and polymerized tubulin fractions. Suckling for 30 min resulted in an increase in soluble tubulin levels and a concomitant decrease in the polymerized pools. At 60 and 90 min, the soluble tubulin levels gradually decreased to presuckled levels, whereas the polymerized pools increased from the 30-min levels to those observed at 0 min. In another experiment, suckling for 10 min resulted in a decrease in the soluble tubulin levels and a corresponding increase in the polymerized tubulin pool. Treatment of nonsuckled rats with domperidone for 10 min also resulted in a shift of the equilibrium between the two tubulin pools similar to that observed at 10 min of suckling. Administration of bromocriptine 30 min beforehand to nonsuckled rats and then suckling them for 10 min blocked the suckling-induced rise in the polymerized tubulin levels. These results suggest a regulatory role for dopamine in the suckling-induced shift in the equilibrium between the soluble and polymerized tubulin pools in the anterior pituitary lobe. PMID- 3335201 TI - Purification and characterization of a fetal somatomedin from the sheep: similarity to insulin-like growth factor II. AB - A high efficiency procedure for the purification to homogeneity of an ovine fetal somatomedin is described. Fetal sheep serum was used as the source material, and activity was followed throughout purification by an insulin-like growth factor (IGF) II RRA. IGF-II-like activity was initially enriched through binding at acid pH to a column of SP-Sephadex C-25 and elution with a neutral pH high-salt buffer. Further chromatography on SP-Sephadex resulted in a preparation containing less than 0.1% of the original serum protein content, but retaining much of the IGF-II-like activity. This enriched fetal IGF preparation was then purified to homogeneity using reverse phase HPLC. However, chromatography on an HPLC gel filtration column was found to be essential to ensure the stability of the purified peptide during storage, although this procedure did not result in any apparent increase in purification. The final yield of purified ovine fetal IGF was 80 micrograms from 400 ml fetal sheep serum. Only one polypeptide chain was detected during amino-terminal sequencing of the fetal somatomedin, and the preparation gave a single band on both gel electrophoresis and isoelectric focusing, indicating that the peptide was essentially pure. The sequence (eight amino acid residues) was identical to the equivalent sequence in IGF-II from human, rat, and bovine sources. In additional, amino acid analysis of the ovine fetal IGF showed close similarity to the amino acid content of IGF-II from other species. The mol wt of the purified peptide, estimated by HPLC gel filtration, was approximately 7000, close to that of previously purified somatomedins, and the isoelectric point, obtained by chromatofocusing, was around pH 6.8. Thus, the purified ovine fetal somatomedin appears to be similar to IGF-II from other species, and may be the ovine homolog of human IGF-II. PMID- 3335202 TI - Tamoxifen inhibits estrogen-induced hepatic injury in hamsters. AB - Estrogens have an unusual toxic effect on the liver of two hamster species, the Armenian and the Chinese hamster. The hepatotoxicity was detectable clinically by hyperbilirubinemia and confirmed histologically by the presence of hepatic degenerative-regenerative changes. Administration of tamoxifen with estrogen [either ethynyl estradiol or diethylstilbestrol (DES)] completely abrogated the hepatotoxic effects, suggesting that estrogen receptor (ER) was necessary for estrogen to damage liver. In Armenian hamsters, estrogens decreased hepatic synthesis of female protein (FP); tamoxifen also abolished this DES effect and resulted in a net increase in serum FP levels. DES administration produced higher serum bilirubin levels and lower serum FP levels in females than in males. Paradoxically, tamoxifen blocked these DES effects more effectively and efficiently in females than in males. Estrogens did not injure uteri of Armenian and Chinese hamsters and were nontoxic to livers of other hamsters species, such as Syrian and Turkish. This model provides another perspective of the acute cellular derangement that can be effected by estrogen-ER complex and may indicate a yet unknown mode of ER action. PMID- 3335203 TI - Luteolysis is linked to luteinizing hormone-induced depletion of adenosine triphosphate in vivo. AB - An elevation of ATP levels in luteal cells markedly enhances their response to gonadotropin. In contrast, depletion of ATP in all cells leads to a series of interrelated events that produces irreversible cell injury. Since the corpus luteum has a transient existence, functional regression and involution of this gland play a fundamental role in the regulation of reproduction. The objective of the present studies was to evaluate whether the luteal ATP content may be regulated in an endocrine fashion and whether luteolysis may be linked to depletion of ATP in the corpus luteum in vivo. The present studies show that removal of the pituitary, maintenance of luteal function in hypophysectomized rats with PRL, or acute treatment with prostaglandin F2 alpha had no effect on luteal ATP levels. However, LH produced a rapid and marked decrease in adenine nucleotide levels in both intact and hypophysectomized PRL-replaced rats, whereas GTP levels were unaffected. In pituitary-intact rats, this same effect of LH occurred within 5 min, was maximal (40% depletion) within 30 min, and was sustained for many hours. Depletion of ATP by LH was dose dependent and evident with low doses of LH. In addition, a decrease in luteal ATP levels was seen during functional luteolysis in the rat, which was directly related to a rise in the serum levels of LH, but not FSH. In contrast, LH had no effect on ATP depletion in isolated cells prepared from the total luteinized ovary, or in enriched preparations of luteal cells. Thus, the depletion of ATP by LH in vivo appears to be mediated by intraovarian agents of unknown nature. We suggest that the rise in LH levels that follows functional luteolysis, due to reduced negative feedback by progesterone, produces a rapid decrease in luteal ATP levels which induces irreversible cell damage and, ultimately, involution of the corpus luteum. This effect would, presumably, be exacerbated as LH levels rise to maximum at ovulation or until LH receptors become down-regulated. PMID- 3335204 TI - Estrogen and androgen dynamics in the cynomolgus monkey. AB - We studied the dynamics of androgen, estrogen, and cortisol (F) production, metabolism, and protein binding in cynomolgus monkeys (M. fascicularis) to provide baseline data and to compare these parameters with those obtained in other primates. Constant infusions of 3H-labeled androgens, 14C-labeled estrogens, and [3H]F were administered to 11 male cynomolgus monkeys (M. fascicularis) for 3.5 h. Blood samples were obtained from a peripheral vein during the infusion, and all urine was collected for 96 h. In each of 3 monkeys, a catheter was inserted into the hepatic vein, and during the infusions blood samples were obtained from the hepatic and peripheral veins and the femoral artery. All blood and urine samples were analyzed for radioactivity as testosterone (T), androstenedione (A), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1). When indicated, blood samples were also analyzed for radioactivity as F. Blood samples taken before the infusions were analyzed for endogenous T, A, DHT, E1, E2, and F concentrations; percent free T, free E2, and free F; and sex hormone-binding globulin and F-binding globulin capacities. The mean +/- SE MCRs for T, A, E2, E1, and F were 44 +/- 4, 407 +/- 40, 175 +/- 17, 315 +/- 28, and 57 +/- 6 liters/day, respectively. The mean blood production rates were 128 +/- 19, 91 +/- 14, 3.3 +/- 0.5, and 9.2 +/- 1.1 micrograms/day and 13.4 +/- 1.9 mg/day for T, A, E2, E1, and F, respectively. The aromatization of androgens was 1.30 +/- 0.10% for A to E1 and 0.28 +/- 0.03% for T to E2. The percent free F (4.34 +/- 0.42%) was greater than the percent free T (1.73 +/- 0.16%) or free E2 (2.75 +/- 0.22%), and the concentration of F-binding globulin was greater than that of sex hormone-binding globulin (227 +/- 35 vs. 60 +/- 7 nM). In the three monkeys who had hepatic venous catheterization, the mean extraction, across the splanchnic bed of T was 32 +/- 3%, that of E was 62 +/- 2%, and that of cortisol was 12 +/- 5%. Across peripheral tissues (leg) the mean extractions were 13 +/- 1%, 18 +/- 1%, and 6 +/- 4%, respectively. In general, the dynamics of androgen, estrogen, and F production and metabolism are similar in male cynomolgus and rhesus monkeys and in man. The similarity is especially close for peripheral aromatization despite differences in adipose tissue content between man and nonhuman primates. PMID- 3335205 TI - Isolation and characterization of insulin-like growth factor I (somatomedin-C) from cultures of fetal rat calvariae. AB - Cultured bones have been shown to secrete local regulators of bone remodeling, such as beta 2-microglobulin, transforming growth factor-beta, and insulin-like growth factor (IGF), but the IGF secreted has not been characterized. In the present study, IGF from medium conditioned by 21-day-old fetal rat calvariae was isolated and characterized. IGF was purified using dialysis, gel filtration, and reverse phase HPLC. Amino acid composition was compatible with that of IGF I (somatomedin-C), and amino-terminal sequence analysis revealed homology with IGF I. The concentration of IGF-I in the calvarial culture medium was 1 nM and was suppressed by cycloheximide. Calvaria-derived rat IGF I at 20 nM stimulated DNA and collagen synthesis by 42% and 26%, respectively, in monolayer cultures of osteoblast-rich rat parietal bone cells. This study indicates that locally produced IGF-I regulates bone formation in cultures of 21-day-old fetal rat calvariae. PMID- 3335206 TI - Thyroxine 5'-deiodinase activity in pineal gland and frontal cortex: nighttime increase and the effect of either continuous light exposure or superior cervical ganglionectomy. AB - Type II T4 5'-deiodinase (5'-D) activity was studied in pineal gland, frontal cortex, and anterior pituitary of male rats. Enzymatic activity was determined by the release of 125I using [3',5'-125I]T4 as substrate. Daytime levels of 5'-D activity were maximal for anterior pituitary (346.2 +/- 142.5 fmol 125I released/mg protein.h), followed by pineal gland (61.5 +/- 8.7 fmol 125I released/mg protein.h) and frontal cortex (3.1 +/- 0.5 fmol 125I released/mg protein.h). Twenty-four-hour fluctuations of 5'-D activity were apparent in the pineal gland and cortex. For pineal, peak 5'-D activity (43.4 +/- 11.4 fmol 125I released/gland.h) occurred at 0100 h, with values at this time being 8-fold greater than basal daytime levels. Superior cervical ganglionectomy (SCGX) or exposure to continuous light (LL) completely abolished the nocturnal rise of 5'-D activity. Treatment with iopanoic acid also inhibited 5'-D activity in pineal (32.1 +/- 3.5 vs. 18.8 +/- 1.7 fmol 125I released/gland.h) without influencing either the N-acetyltransferase activity or the melatonin content. In cortex, peak 5'-D activity occurred at 0500 h (5.3 +/- 0.4 fmol 125I released/mg protein.h), with values at this time being 1.5-fold greater than basal daytime levels. SCGX moderately depressed enzymatic activity, while LL exposure strikingly enhanced the nocturnal increase (11.7 +/- 1.1 vs. 19.3 +/- 2.4 fmol 125I released/mg protein.h at 0300 h). 5'-D activity exhibited no 24-h fluctuation in the anterior pituitary gland, and neither SCGX nor LL exposure affected enzyme levels in this tissue. Our data demonstrate the existence of a 24-h rhythm of type II T4 5'-D activity in pineal gland and cortex, with peak levels occurring at night; in pineal, the sympathetic neural input is indispensable for the rhythm, since SCGX prevented it. In cortex, the apparent paradoxical effect of LL and SCGX on 5'-D activity indicates that other mechanisms are involved in its regulation. PMID- 3335207 TI - Insulin-like growth factor I has independent effects on bone matrix formation and cell replication. AB - The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of [2,3-3H]proline and [methyl-3H]thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on [3H]proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on [3H]thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis. PMID- 3335208 TI - Localization of 7B2, neuromedin B, and neuromedin U in specific cell types of rat, mouse, and human pituitary, in rat hypothalamus, and in 30 human pituitary and extrapituitary tumors. AB - The distributions of three novel peptides, 7B2, neuromedin B, and neuromedin U, in rat, mouse, and human pituitaries, rat hypothalamus, and 30 human pituitary tumors were investigated with immunocytochemistry. Immunoreactivity for 7B2 was present in rat, mouse, and human gonadotropes, in intermediate lobe cells and posterior lobe nerve fibers in rats and mice, in rat hypothalamus (particularly in the median eminence), and in eight human pituitary gonadotropinomas. In gonadectomized rats, larger, more numerous LH beta- and 7B2-immunoreactive gonadotropes were seen than in controls. Extractable 7B2-like immunoreactivity was elevated but not significantly so in gonadectomized rat pituitaries [males: castrated, 37.4 +/- 4.3 (mean +/- SE); controls, 26.9 +/- 4.3; females: ovariectomized, 27.2 +/- 2.7; controls, 19.1 +/- 2.2 pmol/gland]. Neuromedin B immunoreactivity was found in normal rat and mouse thyrotropes and weakly in "thyroidectomy" cells in hypothyroid rats, in which extractable pituitary neuromedin B was significantly depleted (thyroidectomized, 87.0 +/- 14.0; methimazole-treated, 82.0 +/- 11.4; control, 230.7 +/- 25.6 fmol/gland). Hyperthyroid rat pituitaries showed increased TSH beta and neuromedin B immunoreactivities and neuromedin B content (TRH-treated, 385.2 +/- 30.2; T4 treated, 352.6 +/- 20.2; control, 230.7 +/- 25.6 fmol/gland). Neuromedin U immunoreactivity occurred in corticotropes of all species, in rat and mouse intermediate lobe, and throughout the rat hypothalamus, with immunoreactive cell bodies in the arcuate nucleus. Neuromedin U-immunoreactive cells were present in six of six human pituitary and five of six human extrapituitary corticotropinomas. In adrenalectomized rats, corticotropes were larger and more numerous than in controls, but extractable anterior pituitary neuromedin U-like immunoreactivity was not raised (adrenalectomized, 3.30 +/- 0.45; control, 3.32 +/- 0.27 pmol/gland). Our findings suggest that 7B2, neuromedin B, and neuromedin U may be involved in pituitary function. PMID- 3335210 TI - Purification of bovine thyroid-stimulating hormone by a monoclonal antibody. AB - A monoclonal antibody directed against bovine TSH was obtained by hybridoma technology. This antibody was specific for TSH and did not react with bovine LH and FSH. Affinity chromatography of crude TSH was performed on anti-TSH Sepharose. Bovine TSH was purified in a single step to near homogeneity by this technique, as shown by cation exchange chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis of the purified TSH. The biological activity of the hormone was not affected during the purification, as determined by [3H]thymidine incorporation of the TSH-dependent FRTL5 cell line. The results indicate that affinity purification of TSH by means of a monoclonal antibody is a simple one-step procedure for the production of biologically active, highly purified TSH. PMID- 3335209 TI - Hypothalamic hypothyroidism caused by lesions in rat paraventricular nuclei alters the carbohydrate structure of secreted thyrotropin. AB - The effects of hypothalamic hypothyroidism vs. primary hypothyroidism on TSH carbohydrate structure were studied in the rat. Adult male rats with bilateral paraventricular nuclear lesions (n = 10), sham lesions (n = 10), and thyroidectomies (n = 6) were studied 2 weeks postoperatively and compared to normal animals without surgery (n = 6). Pituitaries were incubated in medium containing [3H]glucosamine for 24 h. TSH was immunoprecipitated from medium and pituitary sonicates using anti-TSH beta serum, digested with pronase to obtain TSH glycopeptides, desalted, then analyzed by Concanavalin-A (Con-A) chromatography. Compared to sham controls, hypothalamus-lesioned animals contained a greater proportion of secreted TSH glycopeptides that bound weakly to Con-A, indicating a shift from bisecting and/or multiantennary structures in control animals to biantennary and/or truncated hybrid forms in hypothalamus lesioned animals. In contrast, thyroidectomized animals, compared to normal and lesioned animals, contained a greater proportion of secreted TSH glycopeptides that did not bind to Con-A, indicating a shift from biantennary and/or truncated hybrid forms to bisecting and/or multiantennary forms. The characteristics of the carbohydrate chains on secreted TSH differed markedly in hypothalamic vs. primary hypothyroidism despite equally low thyroid hormone levels in vivo. Thus, in addition to regulating TSH secretion, hypothalamic hormones alter TSH carbohydrate structure, which may affect its bioactivity and MCR. PMID- 3335211 TI - Differential effects of estrogen and growth hormone on uterine and hepatic insulin-like growth factor I gene expression in the ovariectomized hypophysectomized rat. AB - The acute and chronic effects of 17 beta-estradiol (E2) and GH on uterine and hepatic insulin-like growth factor I (IGF-I) gene expression in ovariectomized hypophysectomized (ovx-hypox) rats were examined. Six hours after a single injection of E2 (5 micrograms/100 g BW), uterine IGF-I gene expression was increased 22.5 +/- 5.4-fold (P less than 0.005) above that in untreated rats. In the same experiment E2 alone had no significant effect on hepatic IGF-I gene expression. Similarly, in chronic experiments uterine IGF-I in ovx-hypox rats receiving 0.1 or 1 microgram/rat.day E2 for 10 days was significantly increased compared to that in ovx-hypox rats that did not receive E2 [5.38 +/- 0.79 vs. 1.10 +/- 0.15 (P less than 0.005) and 6.64 +/- 0.28 vs. 0.93 +/- 0.06 (P less than 0.005), respectively]. While administration of human GH alone significantly increased uterine IGF-I expression (3.76 +/- 1.61-fold compared to that in untreated rats; P less than 0.05), a significant and reproducible attenuation of E2-induced IGF-I expression was seen in the two acute experiments where GH reduced the E2-induced response by 36 +/- 3.7% and 53 +/- 19.4%. While chronic administration of E2 to ovx-hypox rats resulted in uterine growth, a significant decrease in body weight was seen in rats treated with 1 microgram/day E2 compared to that in untreated ovx-hypox controls (-4.3 +/- 1.5 vs. 2.5 +/- 0.6 g; P less than 0.0005). E2 treatment also significantly decreased the GH-induced increase in weight gain at each GH dose by approximately 40%. GH-induced hepatic IGF-I gene expression and serum IGF-I concentration were similarly reduced by chronic E2 administration. In contrast, in acute experiments where E2 alone had no effect on hepatic IGF-I expression, it acted in a synergistic fashion with GH and resulted in significantly greater accumulation of IGF-I mRNA. From these observations we conclude that 1) both E2 and human GH are potent stimulators of IGF-I gene expression in appropriate target tissues; and 2) in addition to any effects E2 has on GH secretion and IGF-I action, the growth-retarding effect of estrogen in the rat involves inhibition of GH-dependent hepatic IGF-I expression. PMID- 3335212 TI - Role of oxytocin on prolactin secretion during proestrus and in different physiological or pharmacological paradigms. AB - The present study was designed to evaluate the possible physiological role of oxytocin (OXY) on PRL release by examining the effect of administration of potent pharmacological antagonists of OXY on the stimulation of PRL secretion observed in vitro from anterior pituitary (AP) cells in response to OXY administration or in a number of in vivo paradigms. OXY caused a dose-related increase in PRL release from dispersed AP cells and short term AP cell cultures which was blocked by administration of the OXY antagonists [1-deaminopenicillamine, 2-O methyltyrosine, 8-ornithine]vasotocin (dPOMeOVT) or [1-(beta-mercapto-beta,beta cyclopentamethylene propanoic acid)2-O-methyltyrosine, 8-ornithine]vasotocin (MPOMeOVT), respectively. The antagonists were given in vivo in a dose that completely blocked suckling-induced milk let-down for up to 90 min. Injection of the antagonists did not alter the 5-hydroxytryptophan-induced increase in plasma PRL or the increase associated with acute ether stress or acute suckling stimuli, suggesting that OXY is not a major component involved in the neuroendocrine mechanisms responsible for those particular increases. On the other hand, iv administration of dPOMeOVT or MPOMeOVT prevented the increase in plasma PRL normally observed on the afternoon of proestrus in the cycling female rat. The characteristic surge of LH was also blocked by high doses of these antagonists. These data demonstrate that PRL secretion undergoes a differential regulation, in that OXY appears to play a major role in regulating the increase in plasma PRL observed on the afternoon of proestrus, but apparently provides little, if any, contribution toward the neuroendocrine regulation of the increases in PRL associated with 5-hydroxytryptophan administration, acute ether stress stimulus, or acute suckling stimulus. The data also suggest that OXY receptors located in the AP that are involved in the OXY-induced increase in PRL release may be similar to those OXY receptors located in mammary and uterine tissue, since specific biological effects of OXY in those tissues are effectively blocked by the OXY antagonists dPOMeOVT and MPOMeOVT. A possible role of OXY neurons in the neural mechanisms triggering the LH surge during proestrus is also suggested. PMID- 3335213 TI - Autocrine control of prolactin secretion by vasoactive intestinal peptide. AB - The functions of vasoactive intestinal polypeptide (VIP) and the many other neuropeptides that are localized in the anterior pituitary gland remain unknown although VIP of hypothalamic origin is established to act as a PRL-releasing factor. Evidence is presented here that locally-produced VIP acts in an autocrine fashion to stimulate PRL release. VIP antibodies or a VIP antagonist profoundly but reversibly suppressed PRL secretion in primary cultures of rat pituitary cells or the GH3 cell line. This evidence was obtained with the use of a reverse hemolytic plaque assay for microscopic demonstration of PRL release from individual cells under conditions precluding cell-cell interaction. We suggest that most of the high rate of "spontaneous" PRL secretion attributed to lactotropes deprived of hypothalamic influence is due in fact to the stimulatory effects of VIP acting in an autocrine fashion. PMID- 3335214 TI - Repeated stress increases the density of angiotensin II binding sites in rat paraventricular nucleus and subfornical organ. AB - We have studied the properties of angiotensin II binding sites in the paraventricular nucleus, subfornical organ and anterior pituitary lobe of rats subjected to repeated immobilization stress. This treatment produced significant increase in the density of angiotensin II binding sites in these two nuclei without any significant alteration in binding affinity. Repeated stress did not alter angiotensin II binding properties in the anterior pituitary lobe. Our results suggest that brain angiotensin binding sites may have a role in regulation of the stress response. PMID- 3335215 TI - The regulation of transplacental cortisol-cortisone metabolism by estrogen in pregnant baboons. AB - The present study tests the hypothesis that estrogen regulates the alteration in baboon placental cortisol (F)/cortisone (E) interconversion from preferential reduction (E----F) at midgestation to oxidation (F----E) near term. Five pregnant baboons (Papio anubis) received increasing numbers of 50-mg implants of androstenedione inserted sc at 8-day intervals between days 70 and 100 of gestation (term = day 184) to elevate the production of estrogen. Five animals served as controls at midgestation and received implants containing no steroid, while four baboons were studied near term between days 164-170 of gestation. All animals were bled from a maternal saphenous vein at 2-day intervals, and the serum was assayed for estradiol. On days 100 or 170 of gestation, transuterofetoplacental corticosteroid dynamics were determined by the constant infusion method. Baboons were anesthetized with ketamine and halothane-nitrous oxide and a constant infusion of [3H]F/[14C]E initiated via a maternal saphenous vein. At 60 min, animals were laparotomized and at 70, 80, and 90 min, blood samples were obtained from right and left uterine veins and from a maternal saphenous vein. At 95 min, an incision was made in the uterus, and blood samples were obtained from the umbilical vein and artery. Radiolabeled F and E were extracted from serum and purified by paper chromatography. Maternal serum E2 concentrations (nanograms per ml; mean +/- SE) were greater (P less than 0.01) between days 94 and 100 of gestation in androstenedione-treated baboons (2.4 +/- 0.3) than in untreated animals at midgestation (0.7 +/- 0.2), but lower than those near term (4.5 +/- 1.0). On day 100 of gestation, conversion of E to F across the uterus in control animals (30%) was similar to that of the reverse reaction (23%). In androstenedione-treated baboons at midgestation the conversion of E----F (8%) was lower (P less than 0.05) than the oxidation of F----E (27%) and not different from that in untreated baboons at term (E----F = 13%; F----E = 28%). The dominance of transuterofetoplacental conversion of F----E over the conversion of E----F in term and in androstenedione-treated animals at midgestation was maintained when transfer constants were corrected for fetal metabolic contributions. We conclude that the increase in placental estrogen production induced by androstenedione administration at midgestation alters the pattern of transuterofetoplacental F-E metabolism, supporting the hypothesis that estrogen regulates placental corticosteroid metabolism. PMID- 3335216 TI - Metabolism of cortisol and cortisone in the baboon fetus at midgestation. AB - The metabolism of cortisol (F) and cortisone (E) in the fetal circulation is likely to influence the availability/biological potency of these corticosteroids and hence maturation of fetal organ systems. Therefore, we determined the MCR, production, peripheral interconversion, and placental extraction of F and E in the baboon fetus at midgestation. Radiolabeled F and E were infused into a femoral vein of fetuses (n = 7; 4 female, 3 male) exteriorized on day 100 of gestation (term = day 184). The MCR of F in the fetus (5.6 +/- 0.8 1/day) was lower (P less than 0.01) than that of E (13.1 +/- 2.2 1/day). Placental extraction of F (72.8 +/- 5.3%) and E (87.8 +/- 2.4%) were extensive indicating that the placenta contributes to fetal F/E MCR. Although the serum concentration (micrograms per dl) of F (20 +/- 2) exceeded (P less than 0.01) that of E (12 +/- 1), the calculated production rate (milligrams per day) of F (1.09 +/- 0.12) was not significantly different from that of E (1.55 +/- 0.27). The transfer constant for fetal conversion of F to E (29.0 +/- 6.0%) exceeded (P less than 0.01) that for reduction of E to F (1.8 +/- 0.4%). Therefore, the proportion of total F production derived from circulating E was only 2.2%, whereas the proportion of E derived from circulating F was 26.7%. These findings demonstrate that at midgestation the baboon fetus has minimal capacity for peripheral conversion of biologically inactive E to biologically active F, whereas the reverse conversion (F to E) is substantial. PMID- 3335217 TI - Characteristics of the binding of corticosteroid-binding globulin to rat cell membranes. AB - Specific binding sites for corticosteroid-binding globulin (CBG) were detected on membranes prepared from rat spleen. The binding sites are typical of membrane receptors; they are saturable, specific, have high affinity, and require Mg2+ or Ca2+ for binding. There was little specific binding at 4 C, and maximal binding was obtained at 37 C. Scatchard analysis revealed a single set of binding sites with an apparent Kd of 0.84 microM, and a binding capacity of 39 pmol/mg membrane protein. The sites were specific for CBG; binding of [125I]CBG was not inhibited by a 10,000-fold excess of either rat albumin or rat transferrin. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate of the membrane bound [125I]CBG revealed the presence of lower mol wt iodinated products which were undetectable in the unbound [125I]CBG fraction. Further, whereas the electrophoretic patterns from uterine, pulmonary, and renal membranes showed that the less mobile band (mol wt, 60K) of the normal CBG doublet appeared to be metabolized to a greater extent than the more mobile band (mol wt, 52K), those from splenic membranes showed equal metabolism of both parts of the doublet. PMID- 3335218 TI - Increased expression of the N-myc gene during normal and neoplastic rat liver growth. AB - The activation of N-myc and c-myc genes has been implicated in the genesis of a variety of cancers. In order to determine whether this activation is related to the process of cell growth, we examined N-myc and c-myc expression in rat hepatocytes when growth was stimulated by partial hepatectomy and in rat liver during neoplastic growth induced by diethylnitrosamine. The levels of N-myc and c myc mRNAs, which are very low in hepatocytes from normal rats, were increased at least 20-fold within 3 h after partial hepatectomy and decreased rapidly by 6 h. A second transient peak of c-myc and N-myc mRNAs occurred around 9 and 48 h, respectively. N-myc and c-myc expressions were also induced in carcinoma nodules by diethylnitrosamine. A high level of N-myc transcript was observed in hepatocytes as early as 1 month after the carcinogen administration, whereas c myc transcript was detected at a high level only several months later in carcinoma nodules. Our results suggest that the transient expression of N-myc and c-myc oncogenes during the prereplicative stage of liver regeneration may be associated with the entry of hepatocytes into the cell cycle, and that N-myc expression is not limited to tumors of neural characteristics as has been previously shown but is also observed in cancer from epithelial origin. PMID- 3335219 TI - Growth phase-dependent proteins of the Ehrlich ascites tumor analyzed by one- and two-dimensional electrophoresis. AB - The decrease of the growth rate of the Ehrlich ascites tumor is correlated with changes in the de novo synthesis and abundance of several proteins as is shown by electrophoretic methods. The synthesis of a number of these growth-dependent proteins can be induced in vitro by incubation of the tumor cells in the presence of serum. PMID- 3335220 TI - Cytochemical localization of adenylate cyclase in bovine cumulus-oocyte complexes. AB - The ultrastructural localization of adenylate cyclase was studied in bovine cumulus-oocyte complexes. Adenylate cyclase was observed on the plasma membrane of the oocyte and occasionally on the plasma membrane of cumulus cells. The cytochemical observations presented demonstrate that there is more adenylate cyclase in cumulus-oocyte complexes after in vitro stimulation with forskolin. The presence of adenylate cyclase upon the oocyte was more pronounced. In addition adenylate cyclase appeared to be localized on the cumulus cells, especially between junctional complexes of cumulus cells and on cumulus cell processes contacting the oocyte. The cumulus cells never showed the presence of adenylate cyclase in the absence of forskolin. No changes in the presence of adenylate cyclase were observed during in vitro meiotic maturation. PMID- 3335221 TI - Serum-dependent regulation of proliferation of cultured rat fibroblasts in G1 and G2 phases. AB - We reported that: (i) 3Y1tsF121 cells, a temperature-sensitive (ts) mutant of rat 3Y1 fibroblasts, are reversibly arrested either in the G1 or in the G2 phase, at the nonpermissive temperature. (ii) Cells retain the ability to resume proliferation at the permissive temperature after prolonged arrest in the G1 phase (for 5 days), whereas they lose it after prolonged arrest in the G2 phase (over 24 h). (iii) The G1 arrest is overcome at the nonpermissive temperature by the addition of fresh serum (H. Zaitsu and G. Kimura (1984) J. Cell. Physiol. 119, 82; (1985) J. Cell. Physiol. 124, 177). In the present study, the G2 arrest was overcome by exposing the cells to fresh serum, at the nonpermissive temperature. The G2 arrest occurred only at a higher cell density than that of the G1 arrest. The efficiency of the overcome was higher in the case of the G2 arrest than in case of the G1 arrest. When cells synchronized at the G1/S border by aphidicolin at the permissive temperature were released from the block, they divided in the absence of serum, at the permissive temperature. Even if they had passed through the previous G2 phase in a very high concentration of fresh serum at the permissive temperature, mitotic cells did not enter the S phase in the absence of serum, even at the permissive temperature. When the cells arrested in the G1 phase (not in G0) due to the ts defect were incubated in the absence of serum at the permissive temperature, only 34% entered the S phase and only 15% divided. These results suggest that (i) the ts defect in 3Y1tsF121 limiting cellular proliferation in both the G1 and the G2 phases is probably due to a single mutational event, and is a serum-requiring event. (ii) Preparation of the serum-requiring event which is required for the G2 traverse is completed in the G1 phase, under ordinary conditions. (iii) However, cells are able to fulfill the serum-requiring event in the G2 phase as well as in the G1 phase when the preparation is below the required level. (iv) The commitment to DNA synthesis is not necessarily a commitment to cell division. (v) Cells are arrested in the G1 phase more safely and more effectively than in the G2 phase, by the serum-related mechanism. PMID- 3335222 TI - Use of fluorescent dyes as molecular probes for the study of multidrug resistance. AB - Fluorescence microscopy has shown that 18 different fluorescent dyes, staining various intracellular structures in transformed hamster fibroblasts (DM-15), did not stain or stained weakly multidrug-resistant cells selected from DM-15 by colchicine. Reduced staining by fluorescent dyes was characteristic also of five other tested multidrug-resistant cell lines of hamster and mouse origin, selected by actinomycin D, colcemid, rubomycin, and ruboxyl. The intensity of staining of two revertant cell lines was similar to that of parental sensitive cells. All tested inhibitors of multidrug resistance, including weak detergent, metabolic inhibitors, calcium channel blockers, calmodulin inhibitors, and reserpine, restored normal staining of multidrug-resistant cells. The dyes accumulated in resistant cells in presence of these inhibitors left the cells several minutes after the removal of the inhibitor from the incubation medium. Sensitive cells retained the dyes for several hours. The efflux of the dyes from resistant cells is an active process since it occurred even in the presence of the dyes in the incubation medium. The efflux could be blocked by all tested inhibitors of multidrug resistance and it is possibly a basic mechanism of the reduced staining of resistant cells. These data support the idea that multidrug resistance is based on active nonspecific efflux of the drugs and indicate that the simple procedure of cell staining can be used for the detection of resistant cells and further study of the phenomenon of multidrug resistance. PMID- 3335224 TI - An in vivo study on the synchronizing effect of hydroxyurea. AB - The effect of hydroxyurea (HU; 0.5 mg/g body wt) on L 1210 ascites tumor cells has been studied using various cell kinetic methods. In contrast to the general assumption that HU blocks cells at the G1/S boundary [J. Brachet (1985) Molecular Cytology, Vol. I, p. 266, Academic Press, New York], the present results show that the cells are not held at G1/S but enter S at about the normal rate and are accumulated in early S phase due to a dose-dependent inhibiting effect of HU on DNA synthesis. Partial synchronization of the cells demonstrated by a distinct mitotic peak 10 h after HU application is not due to a G1/S block of the cells and their subsequent synchronous passage through the cycle after release from the block but is due to rather complex mechanisms of action of HU: a differential cytocidal effect and an effect on the passage of the cells through the cycle, both depending on the position of the cells throughout the cycle. HU kills S phase cells, mainly cells in early S phase; i.e., a great portion of the cells "accumulated" in early S phase is killed by the drug, while G1-phase cells are almost not affected by the lethal effect of HU. These G1-phase cells pass through the cycle more rapidly after cessation of the HU effect. The same is true for the surviving cells accumulated in early S phase, while part of the cells in the remaining S phase are delayed in their passage through the cycle. This causes partial synchronization, since a great portion of all cells that survive HU treatment reach mitosis at the same time. PMID- 3335223 TI - Cell cycle phase-specific cDNA libraries reflecting phase-specific gene expression of Ehrlich ascites cells growing in vivo. AB - Asynchronous populations of Ehrlich ascites tumor cells grown in vivo were separated by centrifugal elutriation into fractions of G1-, S-, and G2/M-phase cells with less than 10% cross-contamination. Cytoplasmic mRNA from phase synchronous cells was used to prepare cDNA which was ligated with bacteriophage lambda gt10 arms and amplified in Escherichia coli C600 hfl-. EcoRI digests of DNA isolated from the sublibraries (G1, S, G2/M) were submitted to Southern hybridizations with radiolabeled probes either (a) for genes whose phase-specific expression is clearly documented, thymidine kinase, dihydrofolate reductase, and thymidylate synthase, or (b) for genes whose change of expression during the cell cycle is likely, lamin C, beta-actin, alpha- and beta-tubulin, c-myc, c-fos, p53. The cDNA sequences for genes of group (a) were found to be significantly enriched in DNA of the S-phase library indicating that the cell cycle phase-specific patterns of the respective mRNA levels are conserved in the sublibraries. Sequences belonging to group (b) were also found to be enriched in DNA isolated from the sublibraries: c-fos in G1 phase, lamin C, beta-actin, tubulins, c-myc in S phase, and p53 in G1/S phase. The unexpected prevalence of c-myc and alpha tubulin in the S-phase library is supported by Northern analysis of RNA from phase-synchronous cells. Non-phase-specific, randomly chosen sequences hybridized equally strong with DNA isolated from the different sublibraries. No significant changes of the patterns of hybridization signals were observed with DNA from different amplifications of the sublibraries when analyzed with the same DNA probe indicating that the cDNA complexities are well conserved during amplifications. Consequently, the sublibraries are useful to obtain information about the cell cycle phase-specific expression of mRNAs for other genes of interest. Since the sublibraries reflect mRNA levels of the cells growing in vivo they supply data on the physiological in vivo pattern of gene expression undisturbed by potentially unphysiological in vitro conditions. PMID- 3335225 TI - Regression of autophagic vacuoles in pancreatic acinar, seminal vesicle epithelial, and liver parenchymal cells: a comparative morphometric study of the effect of vinblastine and leupeptin followed by cycloheximide treatment. AB - Treatment of mice with both leupeptin (0.06 mg/g body wt) and vinblastine (0.05 mg/g body wt) for 2 h caused a many-fold enlargement of the autophagic-lysosomal compartment of pancreatic acinar, seminal vesicle epithelial, and liver parenchymal cells. In all three types of cells a predominance of large, dense bodies was seen after leupeptin treatment and that of typical autophagic vacuoles were seen after vinblastine treatment. An exponential decrease of the volume fraction of autophagic vacuoles was observed in leupeptin-treated cells after the administration of cycloheximide (0.2 mg/g body wt). The half-life of autophagic vacuoles estimated from the decay curve was 5.3, 5.7, and 6.6 min for pancreatic, seminal vesicle, and liver cells, respectively. Our data suggest that sequestered cytoplasmic material rapidly enters the lysosomes in leupeptin-treated cells and accumulates in this compartment. In contrast, no regression of the autophagic vacuole compartment of pancreatic and seminal vesicle cells was observed after the administration of cycloheximide to animals pretreated with vinblastine, and only a slight decrease was seen in liver cells. These observations show that the lifetime of autophagic vacuoles is prolonged by vinblastine resulting in their accumulation in the cells. However, our measurements also lend support to the view that in addition to the accumulatory effect on undegraded cytoplasmic material, stimulation of sequestration may play a role in the enlargement of the autophagic lysosomal compartment after treatment with leupeptin as well as with vinblastine in all three types of cells investigated. PMID- 3335226 TI - Isolation of human myoblasts with the fluorescence-activated cell sorter. AB - We have established procedures for the rapid and efficient purification of human myoblasts using the fluorescence-activated cell sorter. Our approach capitalizes on the specific reaction of monoclonal antibody 5.1H11 with a human muscle cell surface antigen. For each of the five samples analyzed, an enrichment of myoblasts to greater than 99% of the cell population was immediately achieved. Following 3 to 4 weeks of additional growth in vitro, sorted myoblast cultures remained 97% pure. Differentiation of the sorted myoblast cultures, assessed by creatine kinase activity and isozyme content, was comparable to that of pure myoblast cultures obtained by cloning, and was significantly greater than that of mixed fibroblast and myoblast cultures. An average of 10(4) viable myoblasts can be obtained per 0.1 g tissue, each with the potential to undergo approximately 40 cell divisions. Accordingly, if only two-thirds of this proliferative capacity is utilized, the potential yield approximates 10(12) myoblasts, equivalent to 1 kg of cells. Human myogenesis in vitro is no longer limited by cell number and is now amenable to molecular and biochemical analysis on a large scale.+ PMID- 3335227 TI - Effect of fibrillation on acetylcholinesterase mRNA in cultured embryonic rat myotubes. AB - Acetylcholinesterase (AChE) and AChE mRNA were evaluated in spontaneously fibrillating myotubes derived from 20-day-old rat fetuses and in matched cultures in which fibrillation was prevented by adding tetrodotoxin on the fourth day of culture. On the eighth day of culture, the AChE activity of fibrillating and nonfibrillating cultures was 5332 and 1861 pmol ACh hydrolyzed min-1 dish-1, respectively (P less than 0.005). Total mRNA was essentially the same in fibrillating and nonfibrillating cultures (27.4 and 25.4 micrograms/dish, respectively). AChE mRNA was assessed by assaying the AChE produced by Xenopus oocytes microinjected with purified mRNA. The AChE produced by mRNA from fibrillating and nonfibrillating cultures was 0.46 and 0.10 pmol ACh hydrolyzed min-1 oocyte-1, respectively (P less than 0.005). PMID- 3335228 TI - Inhibition of nuclear accumulation of karyophilic proteins in living cells by microinjection of the lectin wheat germ agglutinin. AB - The lectin wheat germ agglutinin (WGA), which has been reported to inhibit nuclear protein uptake in vitro by isolated nuclei (Finlay et al. (1987) J. Cell Biol. 104, 189), also blocks, on microinjection into living cells, the migration of proteins into the cell nucleus. Radioactively labeled nuclear proteins were injected into the cytoplasm of Xenopus oocytes and their reentry into the nucleus was analyzed in the presence or absence of WGA by two-dimensional gel electrophoresis. In another set of experiments, fluorescently labeled nucleoplasmin was injected, alone or together with WGA, into the cytoplasm of rat hepatoma cells, and its nucleocytoplasmic distribution was studied by quantitative laser fluorescence microscopy. The results indicate that WGA inhibits the uptake of karyophilic proteins in general, independent of their sizes. Since the nucleocytoplasmic flux of a dextran with Mr 10,000 was not affected it can be excluded that WGA acts by a general blockade or constriction of the functional pore channel. At reduced WGA concentrations, the rate but not the final extent of nuclear protein accumulation was decreased. These findings support the concept that the O-glycosidically bound carbohydrates of certain nuclear pore complex proteins are exposed to the pore interior and that these regions are probably involved in nucleocytoplasmic translocation processes. PMID- 3335229 TI - Butyrate effect on nuclear proteins of two Chinese hamster cell lines. AB - The effect of sodium butyrate on the nuclear proteins of two Chinese hamster cell lines (V79 and CHO) was studied. Butyrate treatment induces hyperacetylation of core histones in both cell lines, while H1 histone shows a different behavior. In CHO cells H1 is dephosphorylated following butyrate incubation; V79 do not show any change of H1 subtypes. It seems that H1 response to butyrate treatment is cell type dependent. Using silver staining a group of proteins that could be present in vivo in the nucleo-protein complex was also detected. PMID- 3335230 TI - Characterization of Caedibacter endonucleobionts from the macronucleus of Paramecium caudatum and the identification of a mutant with blocked R-body synthesis. AB - Cytology, DNA and host-symbiont relationships of x-like endosymbionts from Paramecium caudatum are described. The symbionts (Caedibacter caryophila, sp. nov.) live in the macronuclei of their hosts. They confer the killer trait upon their hosts and appear well adapted to their endonucleobiotic way of life. R bodies (proteinaceous ribbons associated with killing) are produced, but differ significantly from any of the four R-body classes previously described. C. caryophila and their R bodies were isolated. DNA was extracted from purified symbionts and used to demonstrate that one P. caudatum line harbors a natural mutant which is deficient in R-body production. Melting studies indicate a GC content of 34.6%. No sequence homology between the C. caryophila DNA and the coding sequence for type 51 R-body production was observed. C. caryophila is parasitic, causing the death of its hosts in starving cultures. PMID- 3335231 TI - The globin gene expression program in the hamster embryo. AB - Molecular mechanisms involved in control of globin gene expression are a prominent target in current basic biologic research. A better understanding of these mechanisms might also impinge on a clinical goal: amelioration of the human hemoglobinopathies. Recent reports have established the coexistence of embryonic and adult globins in rodent yolk-sac erythroid cells, raising the possibility that globin ontogeny takes place in these cells. The present study was undertaken to define the extent of this putative ontogenic process. We measured daily rates of synthesis of individual globins in hamster yolk-sac erythroid cells from the earliest day in gestation that these cells are available (day 7) until the day they cease to replicate (day 13). Converted to a per-cell basis, the rates demonstrate an ontogenic progression in globin synthesis, from embryonic globins to adult globins, that encompasses nearly entirely the total globin ontogeny of this mammal. Synthesis of adult alpha globin is already detectable on day 7, whereas synthesis of the two adult beta globins does not appear until day 9. Synthesis of embryonic y globin stands in contrast to that of the other two embryonic globins (x and z), rising as they fall, a phenomenon reminiscent of the gamma globin of primates and certain ruminants. This physiologic primitive erythroid cell appears to be an unusually appropriate target for studies directed at globin ontogeny. PMID- 3335232 TI - Expression and induction of cathepsins B and D in K562 cells. AB - Three distinct lysosomal protease activities have been identified in the human leukemia cell line, K562. These include cathepsin D, the classic protease of the mature red blood cell, as well as two proteases, cathepsins B and H, which have been associated with development and differentiation in a variety of tissues. Each of these three lysosomal proteases was expressed in a specific fashion during hemoglobin induction in K562 cells. Both cathepsin B and cathepsin D activities could be induced by growth of K562 cells in medium containing either hemin or heat-treated serum or by increasing the concentrations of untreated serum in the medium. Cathepsin H activity in the same cells remained unchanged. This is the first report of inducible protease activities in K562 cells. Our identification of specific well-characterized protease activities that change differentially during K562 induction provides a framework for additional studies on the role of proteases in hematopoietic differentiation. PMID- 3335233 TI - Megakaryocytes increase in size within ploidy groups in response to the stimulus of thrombocytopenia. AB - Experiments were done to determine if sizes of megakaryocytes within a defined maturation stage were strictly determined by amount of nuclear DNA. Normal mice, mice recovering from an acute episode of thrombocytopenia induced by a single injection of heterologous antiplatelet serum (APS), and mice with sustained thrombocytopenia from daily injections of APS were examined. Areas of mature megakaryocytes were measured in bone marrow smears stained with polychromatic stains. The nuclear DNA content of the same cells was then measured microspectrophotometrically after staining by the Feulgen reaction. Normal megakaryocytes showed a trimodal, lognormal distribution of nuclear chromophore, corresponding to 8n, 16n, and 32n with smaller numbers of 4n and 64n cells; 16n was the predominant ploidy class. In response to thrombocytopenia, ploidy values shifted: the proportions of 8n and 16n cells decreased; 32n and 64n cells increased; 128n megakaryocytes occasionally appeared. These shifts were accompanied by an increase in the average size of all megakaryocytes. In addition to shifts to higher ploidy values, megakaryocytes within ploidy groups became larger than normal megakaryocytes of the same ploidy especially in the mice with sustained thrombocytopenia. These findings show that megakaryocyte size in thrombocytopenic mice is influenced by factors other than the ploidy and maturity of the cell. PMID- 3335234 TI - Effect of ketoleucine treatment on atrophy of skeletal muscle. AB - There is a net loss of skeletal muscle protein in muscle-wasting disorders including the muscular dystrophies and denervation atrophy. Regardless of the nature of the underlying defect, a treatment that could reduce the rate of muscle protein degradation may be of therapeutic value in these conditions. Ketoleucine (alpha-ketoisocaproic acid) has been reported to reduce the rate of protein degradation in skeletal muscle. To evaluate ketoleucine's therapeutic potential, we studied its effect on the muscle protein loss that follows denervation in rats. Maximum tolerated doses of ketoleucine were administered twice daily to rats after surgical denervation of one leg. Wet weights and noncollagen proteins of the soleus and extensor digitorum longus muscles were measured. The ketoleucine-treated animals failed to show significant decrease in muscle wasting, compared with nontreated denervated controls. Further, urinary 3 methylhistidine excretion, a putative measure of muscle breakdown, was not reduced in ketoleucine-treated animals. Our findings do not support the suggested therapeutic role for ketoleucine in muscle-wasting disease. PMID- 3335235 TI - Reinforcement of reciprocal inhibition by contralateral movements in man. AB - A reduction of flexor carpi radialis H reflex size was produced by submotor threshold stimulation of the radial nerve. This reduction reflects reciprocal inhibition exerted by the inhibitory IA interneuron. The effects of contralateral movements on IA reciprocal inhibition were studied in eight normal subjects. Active contralateral arm movement appeared to significantly increase the degree of reciprocal inhibition without affecting the unconditioned reflex. A minor enhancement of reciprocal inhibition was also noted after passive mobilization. Results are discussed in terms of contralateral segmental afferent fibers influencing IA interneuronal excitability. They strongly suggest that contralateral muscular IA afferents may reinforce reciprocal inhibition in man. PMID- 3335236 TI - Cerebral cation shifts in hypoxic-ischemic brain damage are prevented by the sodium channel blocker tetrodotoxin. AB - We investigated the effect of the sodium channel blocker, tetrodotoxin, in two animal models of brain pathology. In the first, an acute model, we recorded the interstitial brain potential in the striatum of rats after cardiac arrest. The time of deflection of this potential, an indication of changes in cerebral cation concentrations, was determined in control rats, and in rats pretreated with intrastriatal tetrodotoxin. In control rats a deflection of the brain potential was noted 2 min after cardiac arrest; tetrodotoxin pretreatment delayed this deflection to about 5 min. The second, a survival model, was based on the Levine preparation in rats. A combination of ischemia and hypoxia produced unilateral, cerebral infarcts, which were characterized by a decrease of brain [K+], and by increases of [Ca2+] and [Na+] and thus of the Na+:K+ ratio. Data on the cation shifts, determined by chemical assay methods, were complemented by those of more conventional methods of assessment of brain damage, such as the determination of survival, of Evans blue staining, and of brain water content. Cation shifts could be prevented locally by tetrodotoxin. In conclusion, the drug can, at least partially, prevent the detrimental effects of an ischemic insult. In addition, our results showed that protective effects observed in the acute model may sometimes offer an indication of the effects to be expected in the survival model. Furthermore, the effect of tetrodotoxin on the brain potentials in the acute model showed that its protective action in the survival model may be brought about by delaying cell depolarization and by shortening the actual duration of the depolarized state. We conclude that Na+ influx and, consequently, neurotransmission may play a crucial role in the development of cerebral damage. PMID- 3335237 TI - Concomitant hypotensive and antinociceptive effects of guanabenz in conscious rats: involvement of nucleus reticularis gigantocellularis. AB - Subcutaneous administration of guanabenz (1, 2, 5, or 8 mg/kg) in conscious Sprague-Dawley rats exerted concomitant suppressive actions on systolic pressure (tail-cuff sphygmomanometric measurement) and pain responses (hot-plate algesio metric assay) that varied both in degree (antinociception much greater than hypotension) and response pattern. Furthermore, both depressive effects were appreciably attenuated by bilateral lesions of the nucleus reticularis gigantocellularis in the medulla oblongata. It is speculated that separate subpopulations of neurons within this reticular nucleus may be involved in the expression of hypotension and antinociception by this amino-guanidine derivative. PMID- 3335238 TI - Convergent effects from vestibulospinal tract and primary cutaneous afferent fibers on motoneurons to proximal lower limb flexor and extensor muscles in humans. AB - In human subjects, the latency and magnitude of cutaneomuscular test reflexes, evoked by stimulation of the sural nerve in the contralateral and ipsilateral quadricep and hamstring muscles, were investigated during static tilts in the pitch axis. The ANOVA demonstrated a highly significant, tilt-dependent modulation of the magnitude of the test reflex for the initial phase of both ipsilateral quadriceps and ipsilateral hamstrings. These results are consistent with results from a similar study on human ankle muscles and provide further evidence that the tilt-dependence of these cutaneomuscular reflexes originates from activity in the otolith receptors. PMID- 3335239 TI - Effects of hind limb suspension on the development of dystrophic hamster muscle. AB - The effects of hind limb suspension on the development of dystrophic muscles was studied in five dystrophic hamsters (CHF 147, formally UMX 7.1) from age 20 days for 5 months. Their histochemical and contractile properties were compared to five aged-matched controls. Twitch and tetanic tensions (Po) were reduced in treated soleus by 22% and 32% and in plantaris by 29% and 39%, respectively; these reductions were proportional to their smaller cross-sectional areas. Twitch duration and half-relaxation times were not altered in experimental soleus muscle but the mean time to 50% of Po was 19 ms faster than the controls. Experimental soleus and plantaris had higher percentages of type II fibers, i.e., 63% and 97% compared with 37% and 93% in controls, respectively. A similar trend was seen in gastrocnemius and extensor digitorum longus muscles. Areas of both fiber types were reduced in all muscles, but only statistically significant differences in type I areas were seen in soleus and type II areas in the other three muscles. The percentages of fibers with centronuclei in whole cross sections, determined at different positions along the muscle lengths, were reduced by 30% in soleus and extensor digitorum longus. The areas of fiber necrosis were also reduced in experimental extensor digitorum longus and plantaris. These changes in nonweight bearing muscles support the hypothesis that contractile activity can influence the development of dystrophic properties. PMID- 3335241 TI - Differential kinetics of fast and slow ankle extensors during the paw-shake in the cat. AB - Force, length, and EMG were assessed in the medial gastrocnemius and soleus muscles of two cats during the paw-shake response. The medial gastrocnemius produced high forces and significant electrical activity while force production and electrical activity were negligible in the soleus. This observation is significant as it provides evidence, through the direct measurement of muscle force, of selective recruitment of a fast muscle when a slow synergist is not activated. Additionally, the relationship among force, length, and neural activation indicates that the role of the medial gastrocnemius during the paw shake response is to decelerate muscle lengthening and begin muscle shortening. PMID- 3335240 TI - Effect of hyperbaric oxygenation on normal and chronic streptozotocin diabetic peripheral nerves. AB - Hyperbaric oxygenation is known to affect energy metabolism and endothelial cell structure and function, but its effects on peripheral nerve have not been reported. We investigated whether it would (i) reverse established streptozotocin induced diabetic neuropathy, a condition in which endoneurial hypoxia exists; (ii) affect energy metabolism in nerve; and (iii) alter the blood-nerve barrier. Sprague-Dawley rats that had been diabetic for 3 months and age-matched controls were used in these studies. One diabetic group and one control group were treated with hyperbaric oxygenation (2 atm for 2 h, 5 days/week) for 4 weeks. Identical groups remained in room air. Sciatic nerve adenosine triphosphate (ATP), creatine phosphate, lactate, and glucose concentrations showed similar changes at rest in both room air and after hyperbaric oxygenation. Nerves of control and diabetic groups exhibited increased lactate production and increased utilization of glucose, ATP, and creatine phosphate after 15 min of anoxia. The albumin blood nerve barrier index was increased in control and diabetic nerves after hyperbaric treatment. Nerve conduction velocity was reduced in the diabetic-room air group and not improved by hyperbaric oxygenation. Caudal nerve action potential, which was significantly reduced in this group, was normalized after hyperbaric treatment. Resistance to ischemic conduction failure was increased in untreated diabetic nerve but not significantly different from controls after hyperbaric exposure. These findings indicate that treatment with hyperbaric oxygenation will partially reverse the neuropathy encountered in chronic diabetes. The biochemical changes are suggestive of enhanced nerve energy metabolism induced by hyperbaric oxygenation. The altered albumin blood-nerve barrier index presumably results from the action of free radicals on endothelial cells. PMID- 3335242 TI - Effects of unilateral cerebral ischemia on the hippocampal theta depth profile in the ether-anesthetized Mongolian gerbil. AB - In gerbils (Meriones unguiculatus) unilateral cerebral ischemia of 5 to 15 min resulted in selective destruction of the ipsilateral hippocampal CA1 stratum pyramidale. It also produced an obvious amplitude reduction in both superficial and deep theta rhythms recorded from damaged hippocampal formation. The presence of normal theta in the left normoxic hemisphere showed that the septohippocampal projections, integrity of which is essential for theta appearance, were spared by ischemia. These data have implications in relation to the two generators hypothesis of theta. PMID- 3335243 TI - Hypothermia elicited by haloperidol in rats with hypothalamic lesions. AB - In a previous paper it was reported that haloperidol plus morphine produces a marked hypothermia, whereas each drug alone had only negligible effects on temperature. A large hypothalamic lesion produced variable hypothermia lasting several days. After the lesion, rats could be classified in two groups: A--those which had marked decreases of colonic temperature (from 3 to 7 degrees C) and B- those which had a slight decrease (about 1 degree C). The administration of haloperidol, which in normal rats has no effect on temperature, elicited in hypothalamic-lesion rats, whether or not they were already hypothermic, a marked decrease in temperature lasting several hours. Rats of group B showed a faster decrease as well as a faster recovery of temperature than those of group A. It was concluded that the hypothalamic lesions produced an effect equivalent to an increase in opioid activity and/or a decrease in dopaminergic activity. PMID- 3335244 TI - Effects of immobilization on the isometric contractile properties of embryonic avian skeletal muscle. AB - Chicken embryos were chronically immobilized by applying a neuromuscular blocking agent, curare, to the chorioallantoic membrane from day 8 through day 16 of incubation to study the effects of a deficit in motor activity on the development of contractile properties of skeletal muscle. Compared with control embryos, spontaneous embryonic motor activity was depressed by 60 to 90% in the curare treated animals during the treatment period. Growth of the posterior latissimus dorsi muscle, a fast-twitch muscle in the adult, was greatly affected by immobilization. The average blotted mass of the muscles from curare-treated 18- to 19-day embryos was approximately 20% of that from control embryos. The isometric contractile properties of posterior latissimus dorsi muscles isolated from control and curare-treated embryos were compared at 18 to 19 days of incubation. The times to peak tension and to one-half relaxation of the twitch and tetanic responses were significantly greater for the muscles from the immobilized embryos. The peak twitch and tetanic tensions, normalized for muscle cross-sectional area, were significantly less than control values for the muscles from curare-treated embryos. The maximal rate of tetanic tension production was, however, unaffected by immobilization. The results of this study demonstrate that the development of isometric contractile properties of embryonic skeletal muscle is significantly altered by an experimentally induced reduction of spontaneous motor activity. A disruption in the functional development of the sarcoplasmic reticulum following a similar decrease in motor activity, as reported by others, is discussed as a potential mechanism for the altered contractile properties of muscles from the curare-treated embryos. PMID- 3335245 TI - Interictal changes in behavior and cerebral metabolism in the rat: opioid involvement. AB - Interictal changes in locomotor and shock-response behaviors were examined in rats that were kindled unilaterally or bilaterally in the amygdala. 2 Deoxyglucose and naloxone were used to test whether alterations in cerebral glucose metabolism or opioid functioning, respectively, correlated with changes in these behaviors. Bilaterally kindled rats, at 14 to 28 days after their last seizure, displayed increased locomotion (square crossing) in an open field compared with unilaterally kindled or control rats. Bilaterally kindled rats also showed elevated thresholds for the elicitation of a multiple squeak response to tail shocks. Single squeak or tail withdrawal responses to tail shock were not affected by bilateral kindling. Likewise, unilaterally kindled rats did not differ from controls on any of the behavioral measures. Naloxone (10 mg/kg, i.p.) reversed the increase in locomotion and elevation of multiple squeak thresholds in the bilaterally kindled rats. By itself, naloxone did not influence any of the behaviors. Finally, cerebral glucose metabolism was decreased, globally, in the forebrain of the bilaterally kindled rats, and naloxone normalized this change. Cerebral metabolism was not altered in unilaterally kindled rats compared with controls. Thus, changes in cerebral metabolism and opioid functioning may be involved in the mediation of interictal changes in locomotor and emotional behavior in rats. PMID- 3335247 TI - Quantitative ultrastructural analysis of coronary atherosclerotic involvement in two macaque species. AB - Ultrastructural analyses were employed to observe and to compare in detail lesions of the coronary artery of cynomolgus and rhesus monkeys. Animals were fed individually with the same atherogenic ration under identical conditions for 4, 8, and 12 months, and controls of each species were fed with a low fat, cholesterol-free ration. Transmission electron microscopic studies of coronary arteries from these animals led to the following conclusions: (1) Synthetic smooth muscle cells (SMC) without lipid and macrophages without lipid appeared more frequently in the cynomolgus lesions than in the rhesus lesions. Furthermore, phenotypic expression of synthetic SMCs in the cynomolgus was more active with greater diversity, while the rhesus showed less phenotypic modulation. Macrophages without lipid appeared frequently in the cynomolgus media. (2) Increased percentages of both synthetic SMCs with lipid and macrophages with lipid were demonstrated in the cynomolgus lesions as compared to those in the rhesus. This indicates that foam cells, including SMC- and macrophage-derived foam cells, are more prevalent in cynomolgus than in rhesus. They are considered to play an important role in atherogenesis. (3) Medial disruption, synthetic SMCs, and macrophages containing lipid appeared more often in cynomolgus media than in rhesus media. (4) There were greater percentages of both synthetic SMCs and macrophages in the intima of the myocardial side of coronary arteries in both species. (5) Approximately 42% of all foam cells in the cynomolgus lesions were derived from SMCs. There were fewer macrophages in rhesus lesions. (6) The difference in expression between the two macaque species reflects different responses of macrophages to medial smooth muscle cell (SMC) components. The configuration of the artery wall could be one of the important indicators of these different expressions. PMID- 3335246 TI - Factors affecting the relative viability of centrifascicular and subperineurial axons in acute peripheral nerve ischemia. AB - An acute reduction in nerve blood flow commonly results in centrifascicular fiber degeneration with subperineurial fiber sparing (CD-SS pattern) in experimental and human peripheral nerve. The mechanism of CD-SS pattern is uncertain. Three hypotheses for the better resistance to ischemic degeneration of subperineurial fibers have been suggested. The subperineurial region has been proposed to have (i) better anastomotic flow (ii) an increased capillary density, or (iii) an extra source of oxygen (from surrounding tissue). We developed methodology that permitted testing of these hypotheses. Nerve blood flow and oxygen tension were measured simultaneously in the central and subperineurial regions using microelectrodes and polarographic techniques. The longitudinal distribution of nerve blood flow was also determined. To test the first hypothesis, nerve blood flow was measured before and after arterial ligation. Well defined watershed areas of reduced flow were found in the longitudinal axis. However, even within these zones, there was a uniform rather than a differential radial reduction in nerve blood flow resulting from ligation. To test the second hypothesis, nerve blood flow was measured during induced arterial hypotension. Nerve blood flow was reduced in proportion to the severity of the ischemic insult but there was no physiologically significant difference between the central and subperineurial areas. To test the oxygen diffusion hypothesis, nerve oxygen tension was monitored simultaneously in the two sites at rest and during ischemia produced by arterial hypotension. Arterial hypotension resulted in severe centrifascicular hypoxia whereas subperineurial oxygen tension was much better maintained as a result of diffusion of oxygen into nerve from the surrounding pool of oil. These findings strongly suggest that the sparing of subperineurial axons in ischemic nerve trunks is due to the diffusion of oxygen from surrounding viable tissues rather than greater capillary density or anastomotic flow. PMID- 3335248 TI - Lysosomal alterations during coronary atherosclerosis in the pigeon: correlative cytochemical and three-dimensional HVEM/IVEM observations. AB - Lysosomal changes have been implicated as one of the major factors contributing to the progression and complications of atherosclerosis, and recently foam cell formation has been correlated with increases in several acid hydrolases. To explore at the subcellular level relationships among lesion progression, cellular lipid accumulation, and lysosomal change, atherosclerotic lesions from hypercholesterolemic White Carneau pigeons have been studied through combined ultrastructural cytochemistry and stereo (three-dimensional) high-voltage electron microscopy. Lysosomal enzyme activity in the prelesion intima and in foam cells of early lesions was in discrete lysosomes of macrophage foam cells. Foam cell lipid at the early stages was primarily (72%) in cytoplasmic droplets, which formed a three-dimensional network with the small (0.25-0.8 microM in diameter), reaction-positive lysosomes suspended at the vertices of a cytoplasmic lattice that delineated individual lipid pools. Concomitant with lesion progression and increasing complexity, foam cell lysosome number, size, and complexity increased. The complexity was characterized by lysosome lipid accumulation (60% of cell lipid) and the fusion of lysosomes to form multilobulated organelles in which the acid phosphatase reaction product typically was circumferential to the lysosomal lipid core. The involvement of lysosomes climaxed in the more advanced region of lesions with foam cells in which the bulk of cytoplasmic volume was occupied by large (15-20 microM in diameter), multicompartmental, lipid-containing lysosomes. It is suggested that this progressive involvement of lysosomes is responsible for cell and tissue necroses characteristic of advanced lesions. PMID- 3335249 TI - Cigarette smoking, dietary hyperlipidemia, and experimental atherosclerosis in the baboon. AB - In separate experiments, we fed 30 male and 25 female baboons a diet enriched in cholesterol and saturated fat for periods of 3.3 and 2.6 years. Using operant conditioning with water rewards, we trained the animals to puff on smoking machines in a human-like manner. Half of the animals smoked more than 40 cigarettes per day, while the remaining animals (controls) puffed air. Initially, the diet produced twofold (males) and threefold (females) elevations from baseline levels in serum cholesterol concentrations, but over the course of the experiments, the serum cholesterol decreased to 1.5 (males) and 2.0 (females) times baseline levels in both cigarette smokers and controls. Blood carbon monoxide concentration, plasma thiocyanate concentration, and urine cotinine concentration were significantly greater in smokers than in controls. Responses to smoking in males included lymphocytosis, elevated fasting blood glucose concentration, and decreased seminal vesicle weight. In females, hemoglobin and mean corpuscular hemoglobin concentrations were elevated. The extent of atherosclerosis was examined after 2.8 (males) and 1.6 (females) years of smoking. Among males, the extent of lesions in carotid arteries was significantly greater in smokers than in controls, but there were no significant differences in atherosclerosis in the aorta or the brachial, iliac-femoral, or coronary arteries. Among females, there were no significant differences in atherosclerosis between smokers and controls in any artery. These experiments show little effect of 2 to 3 years of cigarette smoke inhalation and concurrent modest elevation of blood carboxyhemoglobin on experimental atherosclerosis in the presence of moderate hyperlipidemia. PMID- 3335250 TI - Sequential change of DNA synthesis in cultured aortic smooth muscle cells stimulated by hyperlipidemic serum. AB - Smooth muscle cells from monkey aorta quiescent in 5% calf serum have been shown to be stimulated to renewed proliferation by hyperlipidemic serum or LDL from such serum. This proliferative response evidently is not dependent on platelet derived growth factor present in our system in large quantities. The least exposure time required for reaction between the mitogen and the cells in order to initiate maximal DNA synthesis by this mechanism was studied using autoradiography. Stationary primary cultures and subcultures from monkey aortic media required at least 4 and 8 hr of contact with hyperlipidemic serum or LDL so that a significant number of cells reentered the mitotic cycle. Compared to the primary culture system, subcultures needed a slightly longer time of contact with serum to initiate DNA synthesis. Since there was no significant difference in labeling index between the primary cultures stimulated by serum for 8 and 48 hr and the subcultures exposed between 6 and 48 hr, it is concluded that a relatively brief stimulation commits the majority of responsive cells to reenter the cycle and initiate DNA synthesis. PMID- 3335251 TI - Inhibitory effect of dimethyl sulfoxide on the proliferation of cultured arterial smooth muscle cells: relationship to the cytoplasmic microtubules. AB - Our preliminary study has shown that dimethyl sulfoxide (DMSO) has an inhibitory effect on the proliferation of cultured arterial smooth muscle cells and promotes phenotypic modulation from the synthetic state to the contractile state. In the present study we have examined the effect of DMSO with special attention to relationship between cell growth and cytoplasmic microtubules. DMSO inhibited DNA synthesis and cell division, and concomitantly promoted microtubule assembly. Initiation of DNA synthesis and cell division of nonproliferating cells by platelet-derived growth factor (PDGF) was also inhibited in the presence of 1% DMSO. A 12-hr incubation with 10(-6) M colchicine caused disruption of microtubules; however, pretreatment with 1% DMSO for 24 hr prevented the disruption, indicating that DMSO has a stabilizing action on microtubules. A 24 hr exposure to PDGF resulted in microtubule depolymerization, while the addition of 1% DMSO prevented the depolymerization. These results suggest that DMSO inhibits DNA synthesis of cultured smooth muscle cells by stabilizing cytoplasmic microtubules. PMID- 3335252 TI - Effects of diethylstilbestrol exposure in utero on the genital tracts of female ACI rats. AB - Aspects of development and morphology were studied in the reproductive tract of female ACI rats exposed prenatally to diethylstilbestrol (DES) and followed to 10 months of age. Pregnant ACI rats were injected with vehicle or DES (0.8 microgram = low DES or 8.0 micrograms = high DES) on Days 15 and 18 of gestation. At 12 weeks of age, half of the female offspring in each prenatal exposure group received a subcutaneous implant of a pellet containing 2.5 mg DES and 17.5 mg cholesterol; the remaining offspring received a control cholesterol pellet. Maternal reproductive performance was significantly impaired in DES-treated dams compared to controls. In female offspring mean time of vaginal opening was accelerated from 50.3 +/- 2.7 days in the vehicle-exposed group to 46.2 +/- 2.6 and 47.1 +/- 2.3 days in the low and high DES groups, respectively. Prior to pellet implantation, none of the rats exposed to DES prenatally was in "persistent estrus." At necropsy, rats exposed to DES in utero and implanted with the cholesterol pellet showed an increased frequency of atypical uterine epithelia, cystically dilated uterine glands, and a thickened vaginal epithelium. Among groups implanted with the DES pellet, prenatal exposure to DES increased the incidence of squamous metaplasia of the luminal epithelium and of cystically dilated uterine glands. Collectively, groups implanted with the DES pellet had higher incidences of squamous metaplasia of the uterine lumen, cystically dilated uterine glands, and patches of multilayered uterine epithelium than groups bearing the cholesterol pellet. DES pellet-bearing rats were also found to display a pronounced thickening and vacuolation of the vaginal epithelium. Cervical tissue from 98% of the DES-treated litters was characterized by a markedly convoluted epithelium with numerous squamous cell nests. There were no apparent effects of prenatal DES exposure or postnatal DES treatment on ovarian or oviductal histology. However, ovarian wet weights were significantly reduced as a result of postnatal DES treatment. Thus, the epithelial tissues of the uterus, cervix, and vagina in the ACI rat show a sensitivity to DES whether administered prenatally, postnatally, or in combination. PMID- 3335253 TI - Application of linear integration in the morphometric study of mild and severe pulmonary alveolar injury. AB - In this study we applied linear integration morphometry to characterize the pulmonary alveolar reaction to toxic injury and to study possible relationships between the major tissue and cell compartments of alveolar tissue, normal and injured. Acute alveolar injury of mild and severe intensity was induced in Swiss Webster mice by the ip administration of the chemicals diquat (4 mg/kg) and butylated hydroxytoluene (BHT; 400 mg/kg). Animals were sacrificed at Days 1 and 2 after diquat treatment and at Days 1, 3, and 5 after BHT treatment. Sampling and analysis of alveolar tissue were conducted at both levels of light and electron microscopy. Thickness distributions of arithmetic and reciprocal intercepts, as well as the arithmetic (tau) and harmonic (tau h) mean thicknesses, were established for the following alveolar compartments: septum, alveolo-capillary barrier (ACB), type I and total epithelia, capillary endothelium, and interstitium. A relative measure of the pulmonary diffusion capacity and the capillary load of alveolar septa were also determined. The parameters calculated from these thickness distributions, such as their slopes, percentages of thin intercepts, and tau/tau h ratios, proved very sensitive and useful in the detection and characterization of morphological alterations in the type I epithelial and capillary endothelial cells following either mild or severe alveolar injury. The epithelial, endothelial, and interstitial layers of pulmonary septa were all characterized by their own pattern of structural changes, so that it proved impossible to relate them in a simple way to the tissue reaction, which can be easily studied at the light microscopic level. Linear integration morphometry thus proved very useful as a morphometric approach to the study of pulmonary alveolar injury and repair. PMID- 3335254 TI - Effects of griseofulvin and nocodazole on the accumulation of autophagic vacuoles in Ehrlich ascites tumor cells. AB - Accumulation of autophagic vacuoles (AVs) is a phenomenon observed in various cells treated with the microtubule inhibitor vinblastine. In order to test whether the accumulation of AVs is a result of retarded fusion of autophagosomes and lysosomes an investigation was carried out to ascertain whether other antimicrotubular drugs, e.g., nocodazole and griseofulvin, also induce accumulation of AVs. Ehrlich ascites tumor cells were incubated with nocodazole (20 micrograms/ml) or griseofulvin (50 micrograms/ml). Morphometric analyses were performed after incubation periods of 3, 30, 60, and 120 min. The volume densities of autophagic vacuoles did not differ significantly from the control values after the various incubation periods tested. It was concluded that intact microtubules are not needed in the fusion of autophagosomes and lysosomes and that vinblastine accelerates the rate of AV formation. PMID- 3335255 TI - Steroid profiles of follicular fluids from a patient with the empty follicle syndrome. AB - Steroid profiles of follicular fluid obtained from a patient during a cycle in which no oocytes were recovered in 12 follicular aspirates were compared with those of fluid obtained both from cycles of the same patient and from cycles of other patients when oocytes were recovered. Follicles aspirated in the cycle when no oocytes were recovered were shown to be neither atretic follicles, follicular cysts, nor prematurely luteinized follicles. The steroid profile of follicular fluid from the index cycle was characterized by a markedly increased estradiol-to progesterone ratio and an increased androstenedione level. This, together with a comparison to the steroid profiles of fluid from follicles containing either fertilizable or nonfertilizable oocytes, suggests that the empty follicle syndrome may reflect a dysfunctional ovulation induction. PMID- 3335256 TI - Endotoxins in culture medium for human in vitro fertilization. AB - Endotoxins were detected in a few batches of culture medium during the authors' human in vitro fertilization program. Two distinct levels of endotoxins were assayed: greater than 1 ng/ml and less than 1 ng/ml. The source of endotoxin was traced to culture media obtained from a reputable manufacturing company. The incidence of fertilization per patient was not significantly affected by the presence of endotoxins, but fertilization assessed on the overall number of oocytes was significantly reduced (53%) when endotoxin levels were greater than 1 ng/ml compared with an assay negative for endotoxins (66%) (P = 0.047). The percentage of oocytes cleaving after the observation of two pronuclei was not significantly different, but the degree of fragments observed in the conceptus was significantly more severe if the endotoxin level reached 1 ng/ml. In this investigation, the incidence of pregnancy was 8% when the endotoxin level was greater than 1 ng/ml, 30% if less than 1 ng/ml, and 32% if no endotoxins were detected. This study suggests that, although endotoxins may be present in the culture medium at a deleterious level of at least 1 ng/ml, fertilization and cleavage will be obtained, but there will be a significant increase in the incidence of conceptuses with cytoplasmic fragments; this may result in a reduction in the incidence of pregnancy. PMID- 3335257 TI - Predictive value of abnormal sperm morphology in in vitro fertilization. AB - In patients with acceptable sperm count and motility, two patterns of abnormal morphology, judged with strict criteria, were identified and described. Patients with less than 4% normal forms and less than 30% morphology index (summation of normal and slightly amorphous forms) had a fertilization rate of 7.6% of the oocytes (P pattern, poor prognosis). Patients with normal morphology between 4 and 14% had a significantly better fertilization rate of 63.9% of the oocytes (P less than 0.0001). Cases with greater than 14% normal forms fertilized within the normal range for the laboratory. By evaluating sperm morphology with the proposed strict criteria, its predictive value in in vitro fertilization is enhanced. PMID- 3335258 TI - Evidence for an adverse effect of elevated serum estradiol concentrations on embryo implantation. AB - Multiple follicular stimulation for IVF may be associated with greatly elevated serum E2 concentrations that are presumed to be antinidatory. This factor was analyzed in 825 consecutive embryo transfer cycles. The pregnancy rate decreased significantly after the transfer of one and two embryos in association with preovulatory E2 levels greater than the 90th percentile for the group (2320 pg/ml). The pregnancy rate did not vary with preovulatory E2 concentration following the transfer of three embryos. Highly significant correlations were noted between preovulatory E2 and early luteal phase concentrations of E2 and P. In a subgroup of 245 cycles, there were no significant relationships between implantation and early luteal phase levels of P or the ratio of E2/P. There was a small but nonsignificant tendency for the pregnancy rate to decrease in association with raised luteal E2. It is concluded that excessive E2 levels at the time of ovulation induction with hCG had an adverse effect on implantation when one or two embryos are transferred, but this may be overcome by the transfer of three embryos. The consequences for embryo transfer are discussed. PMID- 3335259 TI - Effects of stress and characteristic adaptability on semen quality in healthy men. AB - Semen from 28 healthy volunteers was assessed for basic semen measure and percent of abnormal morphologic forms every 2 weeks for 6 months. Concurrent self-reports were obtained on abstinence, frequency of ejaculation, health behavior and status, experienced stress, social support, and life events. A single assessment of characteristic adaptability (ego resiliency) also was obtained. Significant between-subject positive correlations were reported among selected semen measures, abstinence, and ego-resiliency. Stress was correlated negatively with semen measures of volume and percent normal morphologic forms. PMID- 3335260 TI - Serum and seminal plasma prolactin concentrations in men with normospermia, oligospermia, or azoospermia. AB - Semen analyses were performed and serum and seminal plasma prolactin (PRL) concentrations were determined in 165 samples from 120 men seen with their wives because of infertility. The mean (+/- standard deviation) serum and seminal plasma PRL concentrations were 6.5 +/- 3.3 and 7.5 +/- 3.1 ng/ml, respectively. The mean concentrations of PRL in serum and seminal plasma were similar in groups of men divided by sperm concentration. Seven men had an increased serum PRL concentration. Three of these 7 men had sperm concentrations less than 20 million/ml and none of these 7 men had an increased seminal plasma PRL concentration. Four men had an increased seminal plasma PRL concentration; the serum PRL concentration, sperm concentrations, and motilities were normal in all 4. No man had a decreased serum or seminal plasma PRL concentration. Increased serum PRL concentrations were found infrequently and the increase was slight (23.2 ng/ml or less). Seminal plasma PRL concentrations were related directly to sperm concentrations and motilities, relationships that were statistically significant. PMID- 3335262 TI - The effect of intraperitoneal progesterone on postoperative adhesion formation in rabbits. AB - The immunosuppressive and anti-inflammatory properties of progesterone (P) have been established. The authors investigated whether the intraperitoneal instillation of P would lessen postoperative adhesion formation in New Zealand white rabbits undergoing pelvic surgical procedures. In phase I, severe, peritoneal lesions were made in the right uterine horn (n = 48). Animals were randomized to receive equal volumes of either (1) Ringer's lactate (RL); (2) 32% dextran 70 (HY; Hyskon Division, Pharmacia, Piscataway, NJ); (3) 500 mg P in oil (PO); or (4) 500 mg aqueous P (PA) at initial laparotomy. In phase II, the distal right uterine horn, including the mesosalpinx, was excised and microsurgical anastomosis was accomplished (n = 45). Aqueous P was not used in phase II; otherwise, the same agents were tested. Six weeks later, the severity of the adhesions formed was graded. The mean adhesion scores for the RL and HY groups were low for the right side in both phases and did not differ (P greater than 0.05). In contrast, higher scores were observed in all the P groups, regardless of the P preparation used or the surgical procedure performed (P less than 0.05). PMID- 3335261 TI - Correlation of human sperm motility characteristics with an in vitro cervical mucus penetration test. AB - Semen analysis was performed on 226 ejaculates by an integrated microcomputerized system employing the multiple-exposure photography (MEP) method. Mucus penetration tests were performed in vitro using commercial preparations of bovine cervical mucus. A highly significant (P less than 0.001) correlation between mucus penetration distance and sperm count (r = 0.582), motility (r = 0.357), velocity (r = 0.569), motile density (r = 0.582), motility index (r = 0.467), and morphology (r = 0.383) was observed. Increased percentages of immature germ cells (r = -0.318) and bent-tailed sperm (r = -0.221) were the most strongly correlated with mucus penetration. Approximately 10% to 15% of patients with otherwise normal semen parameters displayed poor penetration of mucus. Conversely, 5% to 40% of patients with abnormal semen parameters displayed excellent penetration of the mucus. Motile density and velocity demonstrated the strongest relationship with the outcome of the mucus penetration test. These results suggest that a significant subpopulation of patients can be identified as having inadequate (or adequate) penetration of mucus with otherwise normal (or abnormal) motility characteristics. PMID- 3335263 TI - Improved pronuclear mouse embryo development over an extended pH range in Ham's F 10 medium without protein. AB - Pronuclear mouse embryos were cultured at four different pHs (7.17, 7.27, 7.37, and 7.50) in Ham's F-10 medium (Gibco, Grand Island, NY) alone and in Ham's F-10 medium supplemented with 10% human cord serum (v/v) to assess the effects of pH and serum on preimplantation embryo development. Media used in these experiments was stored both without (old protocol) or with triple gas equilibration (new protocol). Development was assessed by the percent of embryos developing to the 2 cell stage and on to the morula and blastocyst stages. Triple gas equilibration prior to media storage improved development to the morula and blastocyst stages. Development to the 2-cell and morula stages was not adversely affected by the presence of serum, but development to the blastocyst stage was significantly higher in Ham's F-10 medium without serum at all pHs tested. In conditions without serum, percent development at all stages examined was similar over the pH range of 7.17 to 7.37, with a significant decrease in development to the morula and blastocyst stage at pH 7.50. Embryos cultured in the presence of serum demonstrated a greater decrease in the percent development to blastocyst at both the low, 7.17 and 7.27, and high, 7.50, pHs, with an apparent pH optimum at 7.37. In summary, the complex media Ham's F-10 medium supports mouse embryo development without the need for serum. Serum inhibits pronuclear embryo development to the blastocyst stage. Mouse embryo culture in the absence of serum can tolerate a pH as low as 7.17 (8.4% CO2) without any detrimental effects. PMID- 3335264 TI - Results of in vitro fertilization with embryo cryopreservation and a recommendation for uniform reporting. AB - The analyzed data from 295 cycles in which certain embryos were frozen demonstrate a comparable aptitude for development of embryos either fresh or frozen-thawed in cycles yielding four or more embryos. This supports the clinical advantage of freezing certain embryos in this situation. However, there was no advantage in freezing embryos if only one to three were available in the IVF cycle. A formula is proposed to give the current outcome and to compare the success rate of IVF-ET according to various parameters, including the policy for embryo cryopreservation. This formula enables all teams to present their data in an identical manner. PMID- 3335265 TI - Diagnostic test properties of serum progesterone in the evaluation of luteal phase defects. AB - The existence of LPD has been controversial, mainly because of inconsistencies in its diagnosis. The endometrial biopsy remains as a gold standard until newer and better tests are developed. Additional information may be provided from serum P determinations in the luteal phase by using the likelihood ratios and positive predictive values obtained in this study. Since the properties of sensitivity and specificity are inversely related, the selection of discriminatory cutoff level of serum P would optimize one at the expense of the other. There is no value that combines both sensitivity and specificity as far as correlation with endometrial biopsy is concerned. PMID- 3335266 TI - Isofluorane inhibits early mouse embryo development in vitro. AB - In vitro development of 2-cell mouse embryos to the blastocyst stage was used to assess the toxicity of isofluorane, nitrous oxide, fentanyl, and meperidine. Isofluorane at concentrations similar to those employed during human oocyte recovery for IVF significantly inhibited mouse embryo development. Since the other agents were without effect, balanced anesthesia with nitrous oxide and narcotics may be preferable to isofluorane for IVF and GIFT. PMID- 3335268 TI - Computerized semen analysis. PMID- 3335267 TI - Antibody binding to greater than 50% of sperm at the tail tip does not impair male fertility. AB - A prospective study was conducted with a man displaying 57.5 +/- 13.4% tail tip directed ASAs to relate results of in vitro tests with attempts to conceive. Tests of seminal quality, penetration of zona-free hamster oocytes, and in vitro penetration of preovulatory cervical mucus were normal. A pregnancy was achieved by natural intercourse during the first cycle in which conception was attempted. More than 50% of sperm were bound by ASAs during the cycle in which conception occurred. These results suggest that ASA binding to certain regions of the sperm surface have no adverse effect on fertility. Therefore, when diagnosing the fertility status of males with ASAs, it appears prudent to use tests that permit determination of the regional distribution of ASA binding to sperm, rather than tests that only permit determination of the presence or absence of ASAs in test fluids. PMID- 3335269 TI - IVF and male factor infertility. PMID- 3335270 TI - Blood transfusions in habitual abortion. PMID- 3335271 TI - Endogenous luteinizing hormone surge and superovulation. PMID- 3335272 TI - Laser vaporization of endometriosis in an infertile population: the role of complicating infertility factors. AB - One hundred twenty-two infertility patients with endometriosis were evaluated and treated using laparoscopy and laser vaporization to provide immediate elimination of all intraperitoneal disease. Ninety-five couples (77.8%) had one or more infertility factors (other than endometriosis) contributing to their infertility. Cervical factors, male factors, and luteal defects were associated with significantly decreased pregnancy rates, despite the use of laser vaporization. The number of contributing factors seemed to be unrelated to the likelihood of success in achieving pregnancy. The authors emphasize the need for total evaluation of other infertility factors in these patients. Such factors should be corrected prior to the use of laser laparoscopy, if possible, and dealt with on a continuing basis following use of this technique. PMID- 3335273 TI - Danazol concentrations in human ovarian follicular fluid and their relationship to simultaneous serum concentrations. AB - Danazol concentrations in follicular fluid and serum were studied in eight women scheduled for laparoscopy because of suspected endometriosis. In order to obtain some variation in follicular maturity, danazol administration was started 2 to 7 days before the expected day of ovulation. A total of nine doses were given, i.e., 200 mg four times daily for 2 days; the last 200-mg dose was given 3 hours before the laparoscopy during which the follicular fluid from the dominant follicle was aspirated. Peripheral venous blood samples were drawn before, during, and after laparoscopy. Danazol concentrations were assayed by means of a high-performance liquid chromatography method. At the time of follicular aspiration, the mean concentration of danazol was estimated at 96 ng/ml in serum and at 71 ng/ml in follicular fluid, i.e., an average of 73% of the simultaneous serum concentration. The data suggest that even short-term therapy with danazol is likely to produce intrafollicular drug concentrations that have a direct inhibitory effect on follicular steroidogenesis. PMID- 3335274 TI - Clinical value of prolactin bioassay in euprolactinemic reproductive disorders. AB - To examine the disparity between clinical presentation and prolactin (PRL) measured by radioimmunoassay (RIA), serum samples from 128 patients with galactorrhea and/or reproductive disorders were evaluated by RIA for immunoassayable PRL (RIA-PRL) and by Nb2 lymphoma cell proliferation assay for bioassayable PRL (bioassay-PRL). One hundred fifteen patients had normal RIA-PRL and 13 patients had high RIA-PRL (greater than 25 ng/ml). Twenty patients had galactorrhea, two of whom had hyperprolactinemia. The reproductive disorders in female patients included infertility, amenorrhea, oligomenorrhea, irregular menstrual cycles, and luteal phase defects. Six oligospermic males also were studied. Twenty-three male and female volunteers with no evidence of reproductive disorders served as controls. Appropriate comparisons showed that PRL bioassay/RIA ratio, an index of agreement between the two assay systems, did not differ for the various patient groups compared with controls. It is concluded that Nb2 lymphoma bioassay does not provide additional diagnostic value to RIA in defining the cause of euprolactinemic galactorrhea and/or reproductive disorders. PMID- 3335275 TI - Alterations in organization of phospholipids in erythrocytes as factor in adherence to endothelial cells in diabetes mellitus. AB - Erythrocytes from patients with diabetes mellitus exhibit increased adherence to cultured human vascular endothelial cells. We investigated the alterations in erythrocyte surface characteristics that may contribute to their abnormal adherence. The organization of phospholipids in the lipid bilayer, as determined by phospholipase A2 treatment and chemical labeling with fluorescamine and trinitrobenzene sulfonic acid (TNBS), is altered in erythrocytes from diabetic patients. Specifically, 12-18% of phosphatidylserine in diabetic erythrocytes (n = 25) is accessible to phospholipase A2 hydrolysis and TNBS labeling, compared to none in normal subjects. These results suggest either a loss in lipid asymmetry or in vivo destabilization of erythrocyte membranes in diabetic patients, causing increased accessibility to phospholipase A2 degradation. The dye merocyanine 540 (MC-540), which is sensitive to the packing of lipids in the bilayer of the membrane, revealed more binding and fluorescence in erythrocytes from diabetic patients than in those from normal subjects. On flow cytometric analysis, 64.5 +/ 17.0% red blood cells (RBCs) in diabetic patients, compared to 35.1 +/- 25.9% RBCs in normal subjects, showed positive MC-540 binding, indicating significant (P less than .001) differences in the packing of lipids in the external leaflet of the bilayer. The results of our study suggest that a loss of lipid asymmetry and/or less ordered packing in the outer leaflet of the diabetic erythrocyte membrane may be responsible for the increased propensity of erythrocytes to adhere to vascular endothelium. PMID- 3335276 TI - Glomerular morphology by light microscopy in non-insulin-dependent diabetes mellitus. Lack of glomerular hypertrophy. AB - We quantitated glomerular structure by light microscopy in 19 subjects with non insulin-dependent diabetes mellitus (NIDDM) and studied the possible connection between morphology and urinary albumin concentration. Autopsy material was collected retrospectively from diabetic subjects in whom urinary albumin concentration had been measured within 1.5 yr. Nineteen consecutive sex- and age matched nondiabetic subjects were controls. A quantitative study of a random sample of glomeruli was performed blindly on periodic acid-Schiff (PAS)-stained sections. The main parameters obtained were 1) mean volume of open glomeruli, 2) frequency of glomerular occlusion, and 3) volume fraction of red-stained material (PAS-positive substance) in open glomeruli [Vv(R/G)]. There was no increase in glomerular volume in these NIDDM subjects, contrary to the glomerular hypertrophy found early as well as late in insulin-dependent diabetes mellitus. An increase in Vv(R/G) was found in diabetic subjects, demonstrating the presence of glomerulopathy as it is diagnosed by light microscopy. The frequency of glomerular occlusion was not significantly different between the groups. A high urinary albumin concentration did not necessarily reflect more advanced glomerulopathy. PMID- 3335277 TI - Lipogenesis from ketone bodies in perfused livers from streptozocin-induced diabetic rats. AB - Production of ketone bodies and their contribution to lipogenesis were measured in isolated livers from normal and streptozocin-induced diabetic (STZ-D) rats perfused with tracer amounts of 3H2O and (R)-3-hydroxy[3-14C]butyrate. Diabetes decreased by 80-95% the total rates of fatty acid and 3-beta-hydroxysterol synthesis in perfused livers and livers of live rats. The activity of cytosolic acetoacetyl-CoA synthetase was slightly (17%) decreased in livers from STZ-D rats. The incorporation of ketone bodies into fatty acids and sterols was markedly inhibited in perfused livers from STZ-D rats despite the stimulation of ketogenesis by diabetes and the presence of oleate. Treatment of the rats with insulin before liver perfusion led to a normalization of the rates of ketogenesis and fatty acid synthesis. The rates of sterol synthesis were only partially normalized by insulin treatment. We conclude that in STZ-D, ketosis does not stimulate hepatic lipogenesis via cytosolic activation of acetoacetate. PMID- 3335278 TI - Relationship of glycosylated hemoglobin to oral glucose tolerance. Implications for diabetes screening. AB - The oral glucose tolerance test (OGTT) for diagnosis of diabetes is inconvenient and requires a great deal of patient cooperation. Glycosylated hemoglobin (GHb), an index of long-term glycemic control, could offer several practical advantages over the OGTT for diabetes screening. We evaluated GHb as a screen for diabetes in 381 adults from a population with a high prevalence of non-insulin-dependent diabetes (Pima Indians). All individuals underwent a standard OGTT (75 g) and were separated into one of three groups: normal (N), impaired glucose tolerance (IGT), or diabetes mellitus (D) based on World Health Organization criteria. HbA1c, a GHb, was measured by highly precise high-performance liquid chromatography (interassay C.V. less than 4%). The normal range for HbA1c was 4.07-6.03% based on the 95% confidence interval for a nondiabetic, mostly Caucasian population. Compared with OGTT, HbA1c was highly specific (91%); an elevated HbA1c usually indicated D or IGT (sensitivity = 85 and 30%, respectively). A normal HbA1c did not, however, exclude a diagnosis of D or IGT. Based on previous epidemiological studies relating plasma glucose to chronic diabetic complications, GHb as measured in this study would properly identify the vast majority of subjects at risk. Long-term studies are necessary to determine the actual risk of complications in individuals with persistently normal HbA1c and D or IGT (based on OGTT). PMID- 3335279 TI - Mineral metabolism and bone mass at peripheral and axial skeleton in diabetes mellitus. AB - Bone mineral content (BMC), mineral homeostasis, and diabetes control were evaluated in 31 Caucasian insulin-dependent diabetic patients (disease duration 18.3 +/- 7.7 yr, mean +/- SD) with normal kidney function. To evaluate bone mass, we performed radiogrammetry and single- and dual-photon absorptiometry. In women, a significantly lower mean BMC was found in the distal radius, at a mixed trabecular-cortical (P less than .01) and a cortical (P less than .05) site, as well as in the lumbar spine (P less than .02). In diabetic men, mean BMC was significantly reduced at the trabecularcortical (P less than .01) and cortical (P less than .05) sites of the radius but not in the lumbar spine. When expressed as densities (i.e., BMC/width or lumbar BMC/area), only the BMC/width at the radius cortical area was significantly reduced in women (P less than .05). The results of the radiogrammetry showed a larger endosteal diameter in the diabetic women, resulting in a significantly lower cortical thickness (P less than .05). Diabetic men did not show abnormalities on radiogrammetry. Diabetic patients had diminished serum calcium and phosphorus concentrations (P less than .001), whereas serum parathyroid, 25-hydroxyvitamin D3, and concentrations of both total and free 1,25-dihydroxyvitamin D3 were normal. No correlation between parameters of diabetes control (HbA1, insulin dose, and triglycerides) or calcium-regulating hormones and BMC were found. These data confirm that, despite large overlap of individual values, mean bone mass at the peripheral skeleton is significantly decreased in diabetic patients. Moreover, we report that the BMC of the lumbar spine is significantly reduced in female diabetic patients. PMID- 3335280 TI - Examination of the role of methylenetetrahydrofolate reductase in incorporation of methyltetrahydrofolate into cellular metabolism. AB - Most mammalian cells receive exogenous folate from the bloodstream in the form of 5-methyltetrahydropteroylmonoglutamate (CH3-H4PteGlu1). Because this folate derivative is a very poor substrate for folylpolyglutamate synthetase, the enzyme that adds glutamyl residues to intracellular folates, CH3-H4PteGlu1 must first be converted to tetrahydropteroylmonoglutamate (H4PteGlu1), 10 formyltetrahydropteroylmonoglutamate (CHO-H4PteGlu1), or dihydrofolate (H2folate), which are excellent substrates for folylpolyglutamate synthetase. Polyglutamylation is required both for retention of intracellular folates and for efficacy of folates as substrates for most folate-dependent enzymes. Two enzymes are known that will react with CH3-H4PteGlu1 in vitro, methylenetetrahydrofolate reductase and methyltetrahydrofolate-homocysteine methyltransferase (cobalamin dependent methionine synthase). These studies were performed to assess the possibility that methylenetetrahydrofolate reductase might catalyze the conversion of CH3-H4PteGlu1 to CH2-H4PteGlu1. CH2-H4PteGlu1 is readily converted to CHO-H4PteGlu1 by the action of methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase, and these enzyme activities show very little preference for folypolyglutamate substrates as compared with folylmonoglutamates. We conclude from in vitro studies of the enzyme that methylenetetrahydrofolate reductase cannot convert CH3-H4PteGlu1 to CH2-H4PteGlu1 under physiological conditions and that uptake and retention of folate will be dependent on methionine synthase activity. PMID- 3335281 TI - Studies on the mechanism of ethanol-induced gastric damage in rats. AB - Concentrated ethanol causes gastric lesions by a mechanism that is poorly understood. We have investigated this mechanism in the rat stomach via gross morphologic, videomicroscopic, histochemical, and pharmacologic approaches. Within 1 min of contact, ethanol caused diffuse mucosal hyperemia. By 5 min, hyperemia greatly intensified at some mucosal sites. Beneath sites where mucosal hyperemia developed, intramural venules strongly constricted at 3-13 s postethanol, whereas submucosal arterioles dilated more than two times in diameter by 25 s. Submucosal venular constriction began sooner than arteriolar dilation (9 vs. 16 s, p less than 0.05). One-third of the gastric mucosal mast cells degranulated by 15 s postethanol; 50% discharged by 30 s. Ethanol-induced hyperemia was markedly reduced by lipoxygenase-selective inhibitors BW755C or nordihydroguaiaretic acid, or by the H1-antihistamine pyrilamine, but not by indomethacin, cimetidine, phentolamine, or methysergide. Based on these results, a model for the pathogenesis of ethanol-induced gastric lesions is proposed. PMID- 3335283 TI - Accumulation of abundant messenger ribonucleic acids during postnatal development of mouse small intestine. AB - To describe the differentiation of the small bowel at the molecular level, intestinal messenger ribonucleic acids (mRNAs) from mice at different stages of fetal and postnatal development were investigated. On the basis of cell-free translation and complementary deoxyribonucleic acid cloning experiments, abundant mRNAs coding for small polypeptides of 6-12 kilodaltons (low-molecular-weight mRNAs) were found in adult small intestine but not in the fetal gut. These developmentally regulated low-molecular-weight mRNAs are uniquely abundant in jejunum and ileum of adult mice, but they are absent or occur only at low levels in the duodenum, colon, stomach, and all other mouse organs examined. Low molecular-weight mRNAs begin accumulating in the small bowel at approximately 3 wk of age, coinciding with weaning and with profound changes in intestinal differentiation. One complementary deoxyribonucleic acid clone of a low-molecular weight mRNA (asb4/134) is specific to the distal small bowel, specifically accumulates at weaning, and hybridizes to RNA from mouse testis and brain at approximately 2%-5% of the intestinal level. Low-molecular-weight mRNA sequences may provide important markers of intestinal differentiation at the genetic level, leading to a better understanding of the factors that contribute to its postnatal maturation. PMID- 3335282 TI - Effects of L-364,718, a new cholecystokinin receptor antagonist, on camostate induced growth of the rat pancreas. AB - Chronic feeding of rats with camostate results in pancreatic hypertrophy or hyperplasia, or both. Previous studies suggest that this effect of camostate occurs via an increase in endogenous cholecystokinin due to an enteral feedback mechanism involving the inhibition of trypsin in the duodenum. Studies employing proglumide, a weak and relatively nonspecific cholecystokinin antagonist, have failed to fully abolish camostate-induced pancreas growth. We examined the effects of L-364,718, a new and highly potent cholecystokinin receptor antagonist, on camostate-induced pancreas growth in rats. The pancreas weights and the concentrations of ribonucleic acid, protein, and chymotrypsinogen in the pancreas of rats treated with camostate alone were significantly elevated over those of controls. These effects of camostate were completely abolished in rats treated with camostate + L-364,718. The pancreas weights and the concentrations of deoxyribonucleic acid and ribonucleic acid in the pancreas of rats treated with L-364,718 alone were significantly lower than values in control rats. These data indicate that camostate-induced pancreas growth in rats appears to be dependent on the actions of endogenous cholecystokinin and that cholecystokinin may play a role in the maintenance of pancreatic growth in normal rats. PMID- 3335284 TI - Retardation of gastric emptying of solid food by secretin. AB - The effect of secretin at nearly physiologic plasma concentrations on the gastric emptying rate of solid food was studied in 12 healthy men. A 99mTc colloid labeled pancake was used as the test meal. The gastric emptying rate was measured during 1 h using a dual-headed gamma-camera, and was expressed as the half-time of the emptying curve. To prevent endogenous secretin release, 400 mg of cimetidine was given before the meal. Subjects were studied under three conditions: (1) during infusion of saline; (2) during continuous infusion of secretin, 6.6 pmol/kg.h; and (3) during three intermittent 10-min periods of secretin infusion, 7.6 pmol/kg.h during each period. Both continuous and intermittent infusion of secretin increased half-emptying time, by 133% and 55%, respectively. The plasma secretin concentration in condition 1 was 0.8 pM; plateau concentration in condition 2 was 9.8 pM; and integrated mean concentration in condition 3 was 4.8 pM. It is concluded that secretin at approximately physiologic plasma concentrations retards gastric emptying of solid food in humans. PMID- 3335285 TI - Peptide YY inhibits pancreatic secretion by inhibiting cholecystokinin release in the dog. AB - Peptide YY inhibits the pancreatic exocrine secretion (bicarbonate, water, and protein) that is stimulated by cholecystokinin, secretin, or neurotensin in the dog, but whether peptide YY inhibits the release of gut peptides that stimulate pancreatic exocrine secretion is not known. Six dogs were prepared with gastric, pancreatic, and cecal cannulas. On separate days, a single dose of sodium oleate (3, 6, 7.5, 9, 12, 15, or 18 mmol/h) was given intraduodenally for 90 min, either alone (control) or in combination with peptide YY (25, 50, 100, 200, or 400 pmol/kg.h, i.v.). We measured plasma levels of cholecystokinin-33/39, secretin, neurotensin, and peptide YY by radioimmunoassay. During infusion of peptide YY, the integrated release of cholecystokinin (3.3 +/- 0.5 ng-[0-90] min/ml) was decreased significantly (p less than 0.05) when compared with control values (5.6 +/- 0.6). Release of secretin and neurotensin was not affected. A positive correlation (p less than 0.05) was found between the release of cholecystokinin and pancreatic protein output in both control (r = 0.68) and peptide YY-treated (r = 0.67) groups. Release of peptide YY was significant after intraduodenal or intracolonic administration of sodium oleate. These studies demonstrate that inhibition of pancreatic protein secretion by peptide YY in dogs is mediated, at least in part, by an inhibition of the release of cholecystokinin. PMID- 3335286 TI - Central nervous system action of calcitonin to alter experimental gastric ulcers in rats. AB - The central nervous system action of calcitonin to influence various experimental models of gastric ulcers and gastric function was studied in rats fasted for 24 h. Intracisternal injection of salmon calcitonin (5 micrograms) completely suppressed gastric ulcerations induced by exposure to cold restraint stress, intracisternal injection of a stable thyrotropin-releasing hormone analogue, or peroral administration of aspirin. By contrast, intracisternal calcitonin enhanced gastric lesions elicited by peroral administration of 40% ethanol or 0.6 N HCl. Calcitonin action was dose-dependent (0.01-1 microgram) and central nervous system mediated inasmuch as intravenous calcitonin, given at a dose 50 fold higher than that effective intracisternally, did not significantly modify gastric mucosal injuries elicited by aspirin or ethanol. Intracisternal injection of calcitonin at 0.01 microgram inhibited gastric acid output by 90% in pylorus ligated rats and suppressed gastric emptying of a liquid meal by 63%-94% in doses ranging from 0.01 to 5 micrograms. Prostaglandin generation in the gastric mucosa was not modified by intracisternal injection of calcitonin. These results demonstrate that intracisternal calcitonin acts within the brain to potently prevent ulcer formation elicited by stress, thyrotropin-releasing hormone analogue, or aspirin, but is not cytoprotective against necrotizing agents. Calcitonin action is not related to modification of gastric prostaglandin generation but it may involve the inhibition of gastric secretory and motor function. PMID- 3335287 TI - Characteristics of alcohol dehydrogenase in fat-storing (Ito) cells of rat liver. AB - Fat storing (Ito) cells, located in the perisinusoidal spaces of the liver and the main storage site of vitamin A, have been associated with fibrogenesis. The mechanisms of alcoholic liver disease, although mostly unknown, do involve ethanol metabolism. This study examined the ability of fat-storing cells to metabolize ethanol. Alcohol dehydrogenase activity was detected in fat-storing cells of the rat liver. The enzyme was demonstrated also by enzyme-linked immunosorbent assay and immunohistochemical staining. The enzyme in fat-storing cells is similar to the hepatocyte enzyme in its Michaelis-Menten constants for substrates and coenzymes and in the competitive inhibition by ethanol of retinol oxidation. It differs from the hepatocyte enzyme by its greater susceptibility to inhibition by 4-methylpyrazole and by having a single isoelectric point of 9.5 as compared with multiple isoelectric points in the hepatocyte ranging from 6.9 to 8.8. The ability of the fat-storing cell to oxidize ethanol and the inhibitory effect of ethanol on retinol oxidation may be important in the pathogenesis of alcoholic liver disease. PMID- 3335288 TI - Fecal protoporphyrin excretion in erythropoietic protoporphyria: effect of cholestyramine and bile acid feeding. AB - The effect of cholestyramine and bile acid feeding upon fecal, red blood cell, and plasma protoporphyrin levels was evaluated in a patient with erythropoietic protoporphyria and evidence of hepatic damage. After a basal period on a controlled diet, bile acids alone were administered (300-900 mg) daily for 9 days, followed by cholestyramine (12 g) plus bile acids (900 mg) daily for 7 days, and cholestyramine alone (12 g) daily for 6 days. There was no substantial change in either the red blood cell or plasma protoporphyrin concentrations during any treatment period. However, cholestyramine and cholestyramine combined with bile acids caused a threefold increase in fecal protoporphyrin excretion, whereas bile acids alone had no effect in this regard. After 1 yr of cholestyramine therapy, fecal excretion of protoporphyrin remained elevated with concurrent improvement in liver function tests and photosensitivity. This study indicates that cholestyramine but not bile acids can substantially increase protoporphyrin excretion and therefore may be capable of ameliorating the hepatotoxicity that may occur in selected patients with erythropoietic protoporphyria. PMID- 3335289 TI - Colonic hamartomas in tuberous sclerosis. AB - Twelve patients, 5 from the same family, diagnosed consecutively to suffer from tuberous sclerosis were investigated for gastrointestinal polyps. Six patients had no clinical neurologic involvement. Nine had colonic polyps: in 5 patients, these were hamartomas, in 3 patients adenomatous polyps, and the ninth patient had hamartomas and adenomatous and villoglandular polyps. Hamartomatous polyps were identical to those found in the Peutz-Jeghers syndrome. However, in 1 patient they included neural structures and in another there were angiomatous and adipous structures in addition to colitis cystica profunda. Two patients with hamartomatous polyps had normal intelligence and no clinical neurologic symptoms. The evaluation of one kindred revealed the association of hamartomatous polyps of the colon with forme fruste of tuberous sclerosis in different members, but none had the typical disease. Tuberous sclerosis should thus be considered in the differential diagnosis of hamartomatous colonic polyps. Conversely, colonic endoscopy may be a useful adjunctive test in the diagnosis of tuberous sclerosis, particularly in the incomplete varieties of disease. PMID- 3335290 TI - Amitriptyline-induced prolonged cholestasis. AB - We report the case of a patient in whom amitriptyline administration for 5 wk was followed by prolonged cholestasis. Jaundice and pruritus lasted 19 and 20 mo, respectively. Three liver biopsies were performed at different stages of the disease showing the course of liver lesions. Cholestasis initially located in the region of the hepatic venule came to be associated with the progressive development of portal tract lesions consisting of inflammatory infiltration, fibrosis, and disappearance of interlobular bile ducts. Amitriptyline hydroxylation and dextromethorphan O-demethylation are deficient in subjects with the poor metabolizer phenotype of debrisoquine. Drug oxidation phenotyping with dextromethorphan showed that this patient had the extensive metabolizer phenotype. This observation demonstrates that amitriptyline can induce prolonged cholestasis and suggests that the susceptibility to develop liver injury while taking this drug may not be related to a genetic deficiency of its hydroxylation. PMID- 3335291 TI - Campylobacter pylori: fact or fancy? PMID- 3335293 TI - Hematomas after percutaneous liver biopsy. PMID- 3335292 TI - What is cytoprotection of the gastric mucosa? PMID- 3335294 TI - Terminal ileum or colon? PMID- 3335295 TI - Campylobacter pyloridis-associated chronic active antral gastritis. A prospective study of its prevalence and the effects of antibacterial and antiulcer treatment. AB - To determine the clinical importance of Campylobacter pyloridis infection, its association with gastric inflammation, and the response to drug therapy, patients with a duodenal or gastric ulcer (n = 63), patients with nonulcer dyspepsia (n = 240), and asymptomatic volunteers (n = 34) were studied. In a prospective longitudinal study, the type, intensity, and distribution of inflammation in antral biopsy specimens were correlated with the presence of C. pyloridis. Campylobacter pyloridis was cultured from antral biopsy specimens in 98% of the ulcer patients, 70% of the nonulcer dyspepsia patients, and 20% of the asymptomatic volunteers. The dependency of chronic active gastritis on the presence of C. pyloridis was shown by an association of gastritis with positive culture and healing of gastritis with negative culture after various therapeutic regimens. Spontaneous disappearance of C. pyloridis never occurred. Colloidal bismuth subcitrate, amoxicillin, and the combination of colloidal bismuth subcitrate and amoxicillin were effective therapies in eradicating C. pyloridis. Recolonization with the same bacterial subtype and recurrence of gastritis frequently occurred within 1 mo after initial eradication. In this study we demonstrate ultimate normalization of gastric mucosa after successful eradication of C. pyloridis. Especially complete normalization of gastric mucosa after amoxicillin monotherapy provides additional strong evidence for a true cause effect relationship between C. pyloridis colonization and gastritis. PMID- 3335296 TI - In vitro (organ culture) studies of the toxicity of specific A-gliadin peptides in celiac disease. AB - Specific peptides of known amino acid sequence were prepared from alpha-gliadin (A-gliadin) by cleavage of the protein with cyanogen bromide and chymotrypsin and purification of the resulting peptides. The three peptides derived from the cyanogen bromide cleavage spanned the complete sequence of A-gliadin (266 residues). Four peptides derived from chymotryptic digestion covered the N terminal sequence through residue 68. These peptides were tested for toxicity in celiac disease by organ culture of biopsied small intestinal tissues taken from patients with active celiac disease. Enterocyte height was used as a measure of peptide effect on cultured tissues. Five of seven peptides tested significantly inhibited increase of enterocyte height in the cultures and were considered toxic on this basis. The largest common sequences among the toxic peptides were -pro ser-gln-gln- and -gln-gln-gln-pro-; these sequences were absent from the nontoxic peptides. The relationship of these sequences to the damaging effect of gliadins on the small intestinal mucosa in celiac disease remains to be investigated. PMID- 3335297 TI - Vagotomy and antrectomy impairs canine fat absorption from solid but not liquid dietary sources. AB - Mild steatorrhea is common after all ulcer operations except parietal cell vagotomy. As these operations impair the grinding and sieving of solid food, we sought to determine the effect of vagotomy and antrectomy on fat absorption from solid (e.g., liver) as compared with liquid (e.g., margarine) dietary sources in the proximal small intestine. Midgut fistulas were placed in 13 dogs; 7 were controls and 6 underwent concurrent vagotomy and antrectomy. To label solid fat, the livers of live chickens were labeled with intravenous [14C]triolein and [3H]glycerol triether, an absorbable and nonabsorbable fat label, respectively. For the liquid fat label, these markers were mixed with margarine. A standard meal of steak, liver, bread, margarine, and water, with either the liver or margarine fat labeled, was fed and the midgut effluent was sieved and centrifuged to obtain four phases: large particles (greater than 0.5 mm), small particles (less than 0.5 mm), aqueous, and oil, which were extracted and counted for 14C and 3H. The ratio of 14C to 3H in each fraction was used to determine how much fat was absorbed from each phase of chyme. With liver fat labeled, 48.3% +/- 8.1% of the [3H]glycerol triether remained in large particles after vagotomy and antrectomy compared with 3.1% +/- 1.0% in controls at midintestine (p less than 0.001). After vagotomy and antrectomy, more than half of the liver fat (solid fat) was malabsorbed (57.1% +/- 6.5% vs. 23.1% +/- 6.6% malabsorbed, p less than 0.01, vagotomy and antrectomy vs. controls), whereas fat absorption from margarine (liquid fat) was not reduced compared with controls (8.8% +/- 2.5% vs. 13.6% +/- 5.5% malabsorbed, p greater than 0.05, vagotomy and antrectomy vs. controls). These observations indicate that by reducing gastric trituration and releasing large particles of poorly digested food into the intestine, vagotomy and antrectomy impairs the absorption of fat selectively from solid, but not from liquid, dietary sources. PMID- 3335298 TI - Surface hydrophobicity of the gastric mucosa in the developing rat. Effects of corticosteroids, thyroxine, and prostaglandin E2. AB - Surface hydrophobicity of the gastric mucosa and its variation in response to treatments with corticosteroids, thyroxine, and 16,16-dimethyl prostaglandin E2 were measured in developing rats. A developmental increase in the hydrophobicity of the luminal surface of the gastric mucosa was recorded between the first and third weeks of life. The hydrophobicity of the stomach was not consistently influenced by an acute administration of 16,16-dimethyl prostaglandin E2 (5 micrograms/kg, 30 min before examination) until the end of the third week of life, at which time a significant 40% increase was recorded. Similarly, the decrease in surface hydrophobicity that resulted from luminal administration of an ulcerogenic dose of HCl (0.6 N, 6 ml/kg) was blocked by 16,16-dimethyl prostaglandin E2 only in 3-wk-old rats and not in rats 1 and 2 wk of age. Neither the normal developmental increase nor the 16,16-dimethyl prostaglandin E2-induced enhancement in gastric surface hydrophobicity was induced precociously by corticosterone or thyroxine. The possible importance of these findings on the development of gastric surface hydrophobicity to the ontogeny of both gastric barrier function and prostaglandin-induced gastric protection is discussed. PMID- 3335299 TI - Intestinal alkaline phosphatase in patients with chronic renal failure. AB - Because of the suggestion that intestinal alkaline phosphatase was elevated in the serum of patients with chronic renal failure, we studied the serum of 42 patients undergoing hemodialysis with elevated enzyme activity. Using a sensitive and specific electroimmunoassay for the intestinal isoenzyme, 26 of 42 serum samples were positive, compared with 3 of 25 samples obtained from hospitalized patients with elevated phosphatase activity. The fractional amount of this isoenzyme was also higher, ranging from 1.5% to 41% of the total serum phosphatase, compared with 0.1%-1.2% in control sera. Kidneys removed during transplantation or postmortem contained a membranous phosphatase with immunologic activity identical to the intestinal isoenzyme in 5 of 6 patients. This enzyme accounted for 8%-21% of the total kidney phosphatase activity. By morphology the immunoreaction was localized to the apical membranes of the collecting tubules. Thus, the kidney is the likely source of the observed increase in serum intestinal-type phosphatase activity noted in patients with chronic renal failure. An elevation in the intestinal isoenzyme rather than the presence of early metabolic bone disease or hepatic disease should be considered in renal failure patients with mildly elevated (up to 50% over normal) total serum alkaline phosphatase. PMID- 3335300 TI - Ontogenesis of the intestinal transport of biotin in the rat. AB - Developmental aspects of the intestinal transport of biotin were examined in suckling (16 day old) and weanling (24 day old) rats using the everted sac technique. The results were compared with those of adult rats previously reported by us using the same intestinal preparation. Transport of biotin was linear for 20 min of incubation in all age groups. Transport of biotin was significantly (p less than 0.05) lower in the jejunum than the ileum of suckling rats but was not significantly different in the jejunum and the ileum of weanling rats. In adult rats, biotin transport was significantly (p less than 0.01) higher in the jejunum than the ileum. In all age groups, transport of biotin in the jejunum was saturable at low concentrations (less than 10 microM) but linear at high concentrations. The apparent Km and Vmax of the saturable process showed a progressive increase from suckling to weanling to adult rats (apparent Km of 0.63, 2.49, and 3.37 microM; Vmax of 18.3, 44.7, and 124.4 pmol/g.min, respectively). On the other hand, the rate of transport by the nonsaturable process showed a progressive decrease with maturation (143.8, 111.6, and 87.5 pmol/g.min for suckling, weanling, and adult rats, respectively). Transport of biotin in suckling and weanling rats was similar to that of adult rats in that it was Na+-, energy-, and temperature-dependent and inhibited by structural analogues. These results demonstrate that biotin transport undergoes clear maturational changes. These changes include a decrease in the affinity and an increase in the activity (and/or the numbers) of the transport carrier, a decrease in the rate of transport by the nonsaturable process, and a change in the preferential site of transport. PMID- 3335302 TI - Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions. AB - There is uncertainty regarding the value of endoscopic biopsy surveillance in Barrett's esophagus because, in retrospective studies, some patients with high grade dysplasia in endoscopic biopsy specimens have had unexpected advanced adenocarcinoma discovered at the time of esophageal resection. We compared the accuracy of preoperative endoscopic biopsy diagnoses with the final pathologic diagnoses in esophagectomy specimens in 4 patients who had both high-grade dysplasia and intramucosal carcinoma and 4 other patients who had only high-grade dysplasia preoperatively. The histologic lesions in all 8 patients were documented in intact mucosa with no gross evidence of neoplasia by endoscopy. The preoperative diagnoses were defined with an endoscopic biopsy protocol in which specimens were taken with large-channel biopsy forceps at least every 2 cm throughout the length of Barrett's epithelium. Final pathologic diagnoses derived from detailed analysis of the resected specimens confirmed high-grade dysplasia without carcinoma in 4 patients and intramucosal carcinoma in 2 patients. The remaining 2 patients with a preoperative diagnosis of intramucosal carcinoma had focal submucosal invasion by carcinoma in the resected specimens, but no involvement of the muscularis propria or adventitial lymph nodes. Because the natural history of high-grade dysplasia is not known, the decision to operate on patients with this lesion must be carefully weighed and individualized for each patient. Two of our patients who underwent esophageal resection for high-grade dysplasia without cancer died, one immediately postoperatively and the other 9 mo later after a postoperative stroke. Once intramucosal carcinoma is documented, surgery should be considered if the patient is an acceptable operative risk. We conclude that systematic preoperative endoscopic biopsy of intact mucosa in Barrett's esophagus can correctly detect high-grade dysplasia, either alone or in combination with early, treatable adenocarcinoma. PMID- 3335301 TI - Effect of peristaltic dysfunction on esophageal volume clearance. AB - Prolonged esophageal acid clearance, found in some patients with esophagitis, can be attributed in part to the peristaltic dysfunction observed in this population. In this study, we undertook to define the effect of commonly observed peristaltic dysfunction on volume clearance by obtaining concurrent videofluoroscopic and manometric recordings in patients with nonobstructive dysphagia or heartburn. Excellent correlation existed between the findings from the two studies. A single normal peristaltic wave resulted in 100% clearance of a barium bolus from the esophagus. At each recording site, luminal closure, as demonstrated by videofluoroscopy, coincided with the upstroke of the peristaltic pressure complex. Absent or incomplete peristaltic contractions invariably resulted in little or no volume clearance from the involved segment. Regional hypotensive peristalsis was associated with incomplete volume clearance by the mechanism of retrograde escape of barium through the region of hypotensive contraction. The regional peristaltic amplitude required to prevent retrograde escape of barium was greater in the distal compared with the proximal esophagus. The mean peristaltic amplitude associated with instances of retrograde escape was 25 mmHg in the distal esophagus compared with 12 mmHg in the proximal esophageal segments. Thus, the peristaltic dysfunction commonly seen in patients with esophagitis (failed and hypotensive peristalsis) likely leads to impaired volume clearance. PMID- 3335303 TI - Increased risk of cholecystectomy in users of supplemental estrogen. AB - We report the results of an analysis of information from a prospective cohort study of women examining the association between cholecystectomy and use of supplemental estrogens (never, current, and past use). There were 55 cases of cholecystectomy in those who had never used estrogen and 105 cases in those who had ever used estrogen. After adjustment for age, the relative risk of cholecystectomy in those who had ever used estrogen was 2.1 (95% confidence interval, 1.5-3.0). In women classified as current users based on information available in 1977, the relative risk of gallbladder disease was 2.7 (95% confidence interval, 1.8-4.0) and in past users as of this date, it was 1.6 (95% confidence interval, 1.1-2.5). When cases known to have reinitiated estrogen use after 1977 are removed from the numerator for past users and added to the numerator for current users, the relative estimate for past use decreased to 1.1 (95% confidence interval, 0.7-1.8), and the risk estimate for current use increased to 3.9 (95% confidence interval, 2.6-5.9). Although an increase in the risk of gallbladder disease in women using supplemental estrogens has been consistently observed in previous studies, the risk after cessation of use has received little attention but could be important. Our data suggest the possibility that the risk of gallbladder disease in estrogen users persists after use of the drug ceases. An increase in the risk of cholecystectomy in estrogen users that persists after drug use ends is plausible if estrogen-induced increases in the lithogenicity of bile cause gallstones to form during drug use and if these gallstones fail to dissolve even after bile lithogenicity returns to normal upon cessation of use. The effect of estrogen use on the gallbladder should be considered in weighing the net risk-benefit ratio of these drugs. PMID- 3335304 TI - Neither glycine-extended gastrin nor the 1-13 fragment of gastrin 17 influences gastric acid secretion in humans. AB - The effect on gastric acid secretion of two gastrin 17-related peptides without the carboxyamide, i.e., the glycine-extended 5-17 fragment and the 1-13 fragment of human gastrin 17, was examined in normal subjects. Acid secretion was stimulated by an intravenous infusion of 21 pmol/kg.h of gastrin 17 or by intragastric instillation of peptone; gastric acid output during simultaneous infusion of 325 pmol/kg.h of the glycine-extended 5-17 fragment or 319 pmol/kg.h of the 1-13 fragment was then compared with acid output during infusion of saline. Neither the glycine-extended 5-17 fragment nor the 1-13 fragment of gastrin 17 influenced gastric acid secretion. By gel and ion-exchange chromatography of serum drawn during infusion, the infused peptide was recovered at the position of the intact synthetic peptide. The disappearance curve of circulating glycine-extended gastrin could be described by two components with half-lives of 3.6 and 48 min. As the glycine-extended fragment was stable in serum or plasma in vitro for 1 h at 37 degrees C, the rapid elimination observed in vivo cannot be ascribed to circulating plasma enzymes. PMID- 3335305 TI - Collagen content and types in the intestinal strictures of Crohn's disease. AB - The collagen content and the relative amount of collagen types were quantitated in control intestine as well as in both inflamed and strictured intestine resected from patients with Crohn's disease. The major collagen type in control intestine was type I (68%), followed by types III (20%) and V (12%). In strictured intestine both collagen content and the relative amount of type V collagen were significantly increased compared with control intestine. Histologic studies demonstrated that in strictured specimens there was a striking proliferation of smooth muscle cells of the muscularis mucosae associated with an accumulation of collagen in the submucosa. The thickness of the muscularis propria was also increased. Immunohistochemical studies demonstrated small amounts of type V collagen in the submucosa of control bowel. In contrast, large amounts of type V collagen were seen in the fibrotic, expanded submucosa of strictured bowel, particularly in the areas where smooth muscle cells of the muscularis mucosae had proliferated. Intestinal strictures in Crohn's disease are therefore characterized by an accumulation of collagen, a proliferation of smooth muscle cells, and an increase in type V collagen, a collagen type produced in relatively large amounts by smooth muscle cells. These changes appear to result in both a loss of the normal compliance of the intestine and a thickening of the intestine wall, resulting ultimately in the intestinal obstruction so frequently seen in patients with Crohn's disease. PMID- 3335306 TI - Adrenergic pathway in the inhibition of pancreatic secretion by peptide YY in dogs. AB - Peptide YY (PYY) is released by perfusion of an ileocolonic segment with oleate and inhibits exocrine pancreatic secretion. This study was designed to determine the role of the adrenergic pathway in the PYY-induced inhibition of pancreatic secretion. After intravenous administration of PYY, there was a dose-dependent inhibition of pancreatic HCO3 and protein responses to secretin, cholecystokinin, and feeding in conscious dogs and a reduction in pancreatic blood flow in anesthetized animals. These inhibitory effects of PYY on pancreatic secretion and blood flow were abolished in the presence of combined phentolamine and propranolol. Ileal perfusion with oleate caused a rise in plasma PYY levels similar to that observed after intravenous infusion of exogenous PYY. Combined alpha- and beta-adrenergic blockade also antagonized the effects of ileal perfusion with oleate on hormonal and postprandial pancreatic secretion. We conclude that exogenous PYY or endogenous PYY released by ileal oleate inhibits pancreatic secretory responses to exogenous secretin, cholecystokinin, or a meal and causes pancreatic vasoconstriction. Both these effects are mediated, at least in part, by the adrenergic pathway. PMID- 3335307 TI - Immunologic and clinical studies on murine experimental autoimmune gastritis induced by neonatal thymectomy. AB - Experimental autoimmune gastritis (AIG), defined by the appearance of auto antibodies to parietal cells, was induced by neonatal thymectomy in BALB/c nu/+mice 3 days after birth. Vitamin B12 absorption and intrinsic factor in the stomach extract decreased compared with those in AIG-negative control groups. No decrease of the serum A/G ratio in AIG-bearing mice was observed. Although development of anemia, as evaluated by a decrease in hematocrit value, was poor until 12 mo of age and the gastric mucosa was hypertrophic, the AIG resembled human pernicious anemia rather than Menetrier's disease. Adoptive transfer of spleen cells, but not sera, of AIG-bearing nu/+ into BALB/c nu/nu mice caused AIG in all animals 1 mo later, indicating the involvement of lymphocytes in the induction mechanism of AIG. Cytofluorometric and immunohistochemical analysis of lymphocytes in the gastric mucosa revealed T-cell infiltration at an early stage (1.5-3 mo) followed by B cell infiltration (6 mo). When the fraction enriched with parietal cells, which were intensively stained with sera of AIG-bearing mice and fluorescent antibody to mouse immunoglobulin G, was injected into the foot pads of AIG-bearing nude mice, typical delayed-type hypersensitivity reaction was observed in all animals. This was not seen in the mice injected with the cell fraction enriched with chief cells, although a few of them were stained by the immunofluorescent technique. Thus, the delayed-type hypersensitivity reaction seems to be directly involved in the mechanism of tissue damage. PMID- 3335308 TI - Medical management of patients with Zollinger-Ellison syndrome who have had previous gastric surgery: a prospective study. AB - We examined prospectively the criteria for medical management in 16 patients with Zollinger-Ellison syndrome who had had previous gastric surgery. Each patient received sufficient antisecretory medication to lower gastric acid output to less than 10 mEq/h during the last hour before the next dose of drug. The 7 patients with a vagotomy but no gastric resection were symptom-free and had no mucosal disease. Of 9 patients with a partial gastrectomy, 7 had mucosal disease, with or without symptoms, and 6 of the 7 patients had acid outputs of 5-10 mEq/h. In these patients, antisecretory medication was increased to reduce output to less than 5 mEq/h and symptoms and mucosal abnormalities resolved in each patient. Patients with Zollinger-Ellison syndrome and a vagotomy can be treated safely by reducing acid secretion to less than 10 mEq/h, but in patients with a partial gastrectomy, acid secretion must be reduced to less than 5 mEq/h, and adequacy of therapy must be checked further by endoscopy. PMID- 3335309 TI - Life events stress and psychosocial factors in men with peptic ulcer disease. II. Relationships with serum pepsinogen concentrations and behavioral risk factors. AB - We examined in a controlled study whether psychologic disturbances in men with peptic ulcer disease were related to other potential ulcer "risk factors" (serum pepsinogen concentrations, cigarette smoking, and intake of alcohol, aspirin, or coffee). Psychopathology in general, personality features of hostility, irritability, and hypersensitivity, and impaired coping ability (low ego strength) each correlated significantly with serum pepsinogen concentration in ulcer patients (p less than or equal to 0.005). Cigarette smoking and intake of alcohol and aspirin were increased in ulcer patients but unrelated to psychopathology. Depression was the variable that best discriminated ulcer patients from nonulcer controls; a negative perception of life events, number of relatives with ulcer, and serum pepsinogen I concentration also had a major, unique discriminating value, whereas smoking played a relatively minor role independent of the other variables examined. Our study supports the concept that several interacting factors (psychologic, behavioral, and genetic/physiologic) are likely involved in peptic ulcer disease. Emotional stress may predispose to ulcers by producing gastric hypersecretion, as manifested by hyperpepsinogenemia. PMID- 3335310 TI - Expression of cell-surface antigens on rat colonic cancer cells. AB - Previously, we reported that two glycoproteins, carcinoembryonic antigen and secretory component, are preferentially expressed on the apical or laterobasal surfaces, respectively, of normal human colonic epithelial cells, whereas these antigens may be expressed over the entire cell surface of colonic cancer cells. These observations have prompted us to develop an animal model of aberrantly distributed normal surface antigens in colonic carcinoma. We prepared four monoclonal antibodies, three of which react specifically with antigens located on the microvillus surface and one that reacts specifically with the laterobasal surface of normal rat colonocytes. Three of the four cell-surface antigens were expressed by cells at all levels of the colonic crypt, but one of the microvillar antigens (p66) was expressed only on the mature colonocytes at the luminal surface. We then documented that a microvillus antigen (p66) detected by one of the antibodies and a laterobasal membrane antigen detected by another antibody were expressed over the entire surface of poorly differentiated colonic carcinoma cells induced by dimethylhydrazine. p66 was more often expressed on poorly differentiated colonic cancers than were the other three antigens. These observations indicate that (a) polarity of surface membrane antigens is a characteristic of normal rat colonic epithelial cells, (b) this polarity is not present in some experimental colonic carcinomas, and (c) the malignant phenotype of colonic carcinoma cells does not result merely from a block in normal differentiation of colonocytes. PMID- 3335311 TI - Localization of villin, a cytoskeletal protein specific to microvilli, in human ileum and colon and in colonic neoplasms. AB - Villin is a cytoskeletal protein of microvilli of epithelial cell brush borders found principally in absorptive cells of the intestine and proximal renal tubule. A marker of both enterocyte differentiation and epithelial cell polarity, it has been studied mainly in experimental animals. We raised monoclonal antibodies to villin and used them to localize it in human ileum and colon and in 22 colonic neoplasms. Villin is localized in the brush border of normal ileum and in the luminal border of normal colon and is expressed with increasing staining intensity as cells migrate from crypt to surface. It was present in the luminal border in all five adenomas and in 16 of 17 adenocarcinomas studied. In addition, villin staining was observed in the cytoplasm of 10 tumors, and in the basement membrane area surrounding tumor in 10 cases. In "transitional" mucosa adjacent to carcinomas it was confined to the luminal border. Abnormal expression of villin by a significant proportion of colonic tumors suggests that it may have a role as a marker of colorectal neoplasia. PMID- 3335312 TI - Epidemiology of cancer of the esophagus in Canada: 1931-1984. AB - Canadian patterns of morbidity and mortality from malignancies of the esophagus for the periods 1970-1980 and 1931-1984, respectively, were examined. Age standardized morbidity and mortality rates have increased significantly for men during the two periods studied (p less than 0.01). Analysis of age-specific rates indicates that increases in age-standardized mortality rates for men are mostly attributable to significant increases in age-specific rates for five of the eight age groups studied. In contrast, age-standardized mortality rates for women have declined significantly during the same period (p less than 0.001), with significant declines in age-specific mortality rates noted for four of the eight age groups studied. Age-standardized morbidity rates for men have changed significantly for two age groups (p less than 0.05), with the rate of change of a third group being of borderline significance (p less than 0.10). Age-standardized morbidity rates for women have not changed significantly during the period 1970 1980 (p = 0.97), which was also characteristic of each of the eight age-specific morbidity rates studied (p greater than 0.40). PMID- 3335313 TI - Long-term follow-up of 2529 patients with gastric and duodenal ulcer: survival rate and causes of death. AB - We investigated 2529 patients with peptic ulcer diagnosed from 1963 to 1975 to determine the prognosis relative to life span and causes of death. During the follow-up period of 9-23 yr, 486 patients (19.2%) died, 2025 (80.1%) were alive, and the fate of 18 (0.7%) was unknown. No significant differences were found between these numbers and the numbers expected from the sex- and age-matched general population at 1-20 yr after the initial diagnosis for patients with gastric ulcer, duodenal ulcer, or both gastric and duodenal ulcer, or for all ulcer groups combined. The survival rate for the surgically treated patients did not differ from the expected survival rate. The number of deaths from peptic ulcer (observed/expected = 18/5.47) was statistically high and the number from cerebrovascular disease was significantly low. Our results show that for patients with a peptic ulcer, the prognosis relative to life span is as good as that of the general population and surgery has little influence on the prognosis. PMID- 3335314 TI - Colonoscopic screening of persons with suspected risk factors for colon cancer. I. Family history. AB - A family history of colorectal cancer is believed to place persons at increased risk for development of the disease. It is unclear, however, how "strong" a family history must be to increase this risk or to make colonoscopic screening appropriate. We performed initial colonoscopy in 154 asymptomatic subjects whose only suspected risk factor was one or two first-degree relatives with colorectal cancer; 48 of these subjects also had affected second- and third-degree relatives. We found 45 adenomas in 28 subjects (18%). One subject had a 3-cm villous adenoma. In 6 subjects, the most advanced findings were tubular adenomas 5-9 mm in diameter; in 21 subjects, we found only tubular adenomas that were 2-4 mm in diameter. The prevalence of adenomas increased significantly with age of subjects (p less than 0.01). Although the overall prevalence of colorectal neoplasms in our group was no greater than might be expected in the general population, subjects with two first-degree relatives tended to have more diminutive adenomas than those with one such relative. Our findings suggest that colonoscopy is not an appropriate first step in screening persons with one affected first-degree relative. For those with more complex family histories, more data are needed--particularly on the prevalence of advanced neoplasms--to determine whether a screening technique that is less costly and less invasive than colonoscopy may be adequate. PMID- 3335315 TI - Quantification of colonic lamina propria cells by means of a morphometric point counting method. AB - The lamina propria of colonic mucosa normally contains eosinophils, lymphocytes, plasma cells, and a few neutrophils. If the number of such cells is judged to be increased, colonic inflammation is said to be present. However, the number of cells present in normal mucosa has not been clearly established. Mild abnormalities are difficult to identify, yet might be associated with colonic dysfunction. We therefore developed a morphometric point-counting method to quantitatively analyze the areas occupied by different structures in the mucosa of the human colon. A computer was used to move a dot in a rectilinear pattern over the X400 magnified image of biopsy specimens obtained from throughout the colon by colonoscopy. The structure on which the dot landed was identified and tabulated by a pathologist. In preliminary studies, we established counting parameters that would yield the most representative results. Based on statistical analysis, it was decided to count 98 points in each of seven regions of six biopsy specimens, i.e., over 4000 points per subject. Results were expressed as percentages of counts landing on a given item, and represented the area of the biopsy specimen covered by that item. Using this method, we determined the range of normal in healthy volunteers. The sensitivity of this method was tested by studying patients with chronic diarrhea previously diagnosed as having or not having mild to moderate mucosal inflammation. In the patient group, colonic fluid absorption measured by a perfusion technique was directly correlated with epithelial cell counts and inversely correlated with lamina propria cellularity and with the counts of lamina propria neutrophils and plasma cells. We conclude that morphometric analysis of colon biopsy specimens can be used to quantitate histologic features of colonic mucosa and to accurately identify even mild abnormalities, and that it can be a useful clinical research tool. PMID- 3335316 TI - Pancreatic secretory response to ordinary meals: studies with pure pancreatic juice. AB - We have studied the pancreatic secretory response to a normal meal in 5 subjects with an external drainage of the main pancreatic duct carried out after biliary tract surgery. Pancreatic juice was collected at 60-min intervals from 10 AM to 7 PM, starting 2 h before and ending 7 h after lunch, and was analyzed for volume, bicarbonate content, and protein content. Large doses of pancreatic extract were given between and during meals. Both bicarbonate and protein output increased rapidly after the beginning of the meal and the increase persisted, with minor fluctuations, for the entire 7-h study period between lunch and dinner. The peak postprandial bicarbonate and protein outputs were higher (on average by 20% and 26%, respectively) than bicarbonate and protein outputs induced by exogenous infusion of submaximal doses of secretin and cerulein. The profile and magnitude of the bicarbonate secretory pattern elicited by food were not substantially different from those of protein secretion. In an additional patient who had undergone a duodenocephalopancreatectomy plus two-thirds distal gastrectomy before the study, the pancreatic response to meals showed an initial phase characterized by an increase in pancreatic secretion during the first postprandial hour followed by a tendency to decrease in the subsequent 2 h, and a later phase (from the fourth postprandial hour to the end of the study) characterized by a more marked and more persistent increase in pancreatic secretion than occurred in the initial 3 h. These data indicate that (a) the pancreatic secretory response to ordinary meals is much more prolonged than is generally believed. The late phase of the response is not dependent on gastric emptying of food into the duodenum, but is probably related to the arrival of chyme in the distal ileum. (b) The pancreatic secretory response to a normal meal is quantitatively slightly higher than that produced by exogenous pancreatic stimulation with submaximal doses of secretin and cerulein. (c) The pattern of postprandial bicarbonate secretion is similar to that for protein. PMID- 3335317 TI - Metabolic bone disease in primary biliary cirrhosis at presentation. AB - Metabolic bone disease, particularly osteoporosis, is a complication of advanced primary biliary cirrhosis, but the extent of the problem is unclear. We present 33 patients who were investigated for bone disease at the time of diagnosis of their liver disease and who had received no prior treatment likely to influence their bones. Iliac crest bone biopsy showed no patient with osteoporosis, and mild osteomalacic changes in 1 patient. Slight elevations in appositional rate, osteoid volume, and resorption surface were compatible with a state of high bone turnover. Photon absorptiometry revealed a low forearm bone mineral content in 3 of 25 patients, calcium absorption was below normal in 14 of 24 patients, and there was evidence of fat malabsorption in 11 of 25 patients. Five patients also had low serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. Thus, little evidence of significant metabolic bone disease was found in this group by these methods, but abnormalities were seen, such as poor calcium absorption, that may predispose to its later development. PMID- 3335318 TI - Intestinal microvascular adaptation to chronic portal hypertension in the rat. AB - Microvascular pressures, diameters, and flow velocities were measured in the small intestine of rats with chronic stenosis of the portal vein. Ten days after portal vein stenosis, portal venous pressure increased (13.8 +/- 0.4 mmHg vs, 7.3 +/- 0.5 mmHg; p less than 0.05) whereas systemic arterial pressure decreased (94.2 +/- 2.0 mmHg vs. 106.5 +/- 1.6 mmHg; p less than 0.05). Red blood cell centerline velocity, measured in first-order arterioles, was significantly higher in portal hypertensive rats (24.3 +/- 1.2 mm/s vs. 19.6 +/- 1.3 mm/s), yet there was no significant change in the diameters of these vessels. Microvascular pressures and diameters of first- and second-order arterioles were not different between control and portal hypertensive rats. However, both pressure (34.3 +/- 2.7 mmHg vs. 28.0 +/- 1.8 mmHg) and diameter (30.4 +/- 0.6 microns vs. 21.4 +/- 2.1 microns) were significantly increased in the third-order arterioles of portal hypertensive rats. A consistent elevation in pressure was observed throughout the distal segments (capillaries to first-order venules) of the intestinal microcirculation of portal hypertensive rats. The results of these studies indicate that the increased intestinal vascular pressures associated with chronic portal hypertension result from a combination of reduced arteriolar resistance and venous congestion. PMID- 3335319 TI - Galactose clearance measurements and liver blood flow. AB - Galactose clearance, measured during low galactose infusion and calculated as infusion rate divided by peripheral galactose concentration (systemic clearance), has been proposed as a measure of liver blood flow. This requires nearly complete hepatic extraction as well as negligible extrahepatic elimination. The purpose of the study was to examine if these assumptions are fulfilled in subjects with no liver disease, and to compare the galactose clearance measurement with an independent measurement of liver blood flow. Liver blood flow was measured in 6 subjects by means of a constant indocyanine green infusion, indocyanine green concentration measurements in a peripheral artery and a hepatic vein, and calculation according to Fick's principle. The mean (+/- SEM) blood flow rate was 1.2 +/- 0.1 L/min. Galactose was given at a constant infusion rate of 142 +/- 10 mumol/min, and steady-state concentrations were measured in the peripheral artery (A) and the hepatic vein (V). The hepatic extraction fraction [(A - V)/A] was 0.91 +/- 0.03. The hepatic galactose elimination rate [(A - V) X flow] was 101 +/ 12 mumol/min; this is about two-thirds of the total elimination rate (viz., infusion rate). Urinary excretion was negligible. This indicates an extrahepatic galactose elimination of approximately 41 mumol/min. Systemic galactose clearance, calculated as mentioned above, was 1.5 +/- 0.1 L blood/min. It was significantly higher than the liver blood flow in each subject (paired t-test, each p less than 0.02), on average 133% of the flow. Thus the systemic galactose clearance value overestimates liver blood flow, probably due to a small, but in this context quantitatively important, extrahepatic galactose elimination. PMID- 3335321 TI - Effects of intestinal microbial bile salt sulfatase activity on bile salt kinetics in gnotobiotic rats. AB - Hepatic sulfation is thought to promote fecal excretion of lithocholate in humans by impairing the enterohepatic recirculation of the compound. Sulfatases produced by the gut flora may, at least in part, counteract this process. To investigate this interaction, female germfree rats, which are known to excrete considerable amounts of sulfated bile salts, were selectively associated with a bile salt desulfating flora. In these rats nearly all cecal, colonic, and fecal bile salt sulfate esters were hydrolyzed, resulting in a decrease of total fecal bile salt excretion of greater than 25% compared with gnotobiotic rats without a bile salt desulfating flora. Desulfation of allochenodeoxycholate, the major sulfated bile salt in germfree rats, led to an enhanced recirculation and 12 alpha hydroxylation of the compound in the liver, resulting in an increased fecal output of allocholate. Microbial desulfation of intraperitoneally injected [24 14C]taurolithocholate-3-sulfate caused a fivefold decrease of the fecal plus urinary excretion rate of the isotope to approximately that found for unsulfated [24-14C]taurolithocholate. Coassociation of the gnotobiotic rats with a microflora that normalized the small intestinal transit time and cecal size led to a rise of total fecal bile salt excretion of greater than 30% and a twofold accelerated excretion of both sulfated and unsulfated injected [24 14C]taurolithocholate. We conclude that in rats the gut flora rapidly desulfates intestinal bile salt sulfates, enhancing the enterohepatic recirculation and subsequent hydroxylation of the desulfated bile salts. In addition, these data illustrate the importance of having a well-defined microflora to normalize intestinal transit time and cecal size of gnotobiotic animals when performing kinetic studies of enterohepatic circulating compounds. PMID- 3335320 TI - Prognostic value of arterial pressure, endogenous vasoactive systems, and renal function in cirrhotic patients admitted to the hospital for the treatment of ascites. AB - To identify prognostic factors in cirrhotic patients admitted to the hospital for the treatment of an episode of ascites, a survival analysis was performed in a series of 139 patients hospitalized in our Unit between 1980 and 1985. Mean follow-up was 12.8 +/- 14.2 mo (mean +/- SD). A total of 38 variables based on history, physical examination, hepatic biochemical tests, renal function tests, and endogenous vasoactive systems were analyzed for prognostic value. Eighteen of these variables had prognostic value in the univariate analysis. A multivariate analysis (Cox's regression method) disclosed that 7 of these 18 variables had independent prognostic value. Of these independent predictors of survival, mean arterial pressure and plasma norepinephrine concentration were the variables that best predicted prognosis. Two other variables that independently correlated with survival were urinary sodium excretion and glomerular filtration rate. The remaining three independent predictors of survival were nutritional status, hepatomegaly, and serum albumin concentration. Therefore, these findings indicate that, in patients with cirrhosis and ascites, parameters estimating systemic hemodynamics and renal function are better predictors of survival than those routinely used to estimate hepatic function. PMID- 3335322 TI - Response to steroids in Budd-Chiari syndrome caused by idiopathic granulomatous venulitis. AB - A 31-yr-old man presented with the Budd-Chiari syndrome. A liver biopsy specimen demonstrated noncaseating centrilobular granulomas and an idiopathic necrotizing granulomatous venulitis involving hepatic vein radicles with superimposed thrombotic occlusion. High-dose prednisone therapy produced dramatic clinical improvement with resolution of the hepatomegaly, ascites, and portal hypertension and normalization of the hepatic venous angiogram. A repeat liver biopsy specimen showed resolution of the venulitis and disappearance of the hepatic vein thrombosis. Idiopathic granulomatous venulitis that is reversible with prednisone therapy should be considered in the differential diagnosis of the Budd-Chiari syndrome. PMID- 3335324 TI - High esophageal stricture: a complication of "inlet patch" mucosa. AB - High esophageal stricture associated with a circumferential "inlet patch" of heterotopic gastric mucosa is reported in 2 patients. Biopsy specimens taken from the strictures demonstrated inflamed or ulcerated gastric fundal-type mucosa in both cases. Dilatation of the strictures followed by treatment with histamine H2 antagonists produced almost complete resolution of dysphagia in both patients. PMID- 3335323 TI - Zinc-induced copper deficiency. AB - Copper deficiency was found in an adult patient who had received excessive daily oral zinc for 10 mo. The deficiency was characterized by hypochromic-microcytic anemia, leukopenia, and neutropenia. Although initially thought to be caused by iron deficiency, the anemia did not respond to oral or intravenous iron. Cessation of zinc tablets and ingestion of an oral copper preparation daily for 2 mo failed to correct the anemia or leukopenia. It was not until shortly after intravenous administration of a cupric chloride solution during a 5-day period, at a total dose of 10 mg, that serum copper and ceruloplasmin levels increased and the anemia, leukopenia, and neutropenia resolved. These data suggest that the elimination of excess zinc is slow and that, until such elimination occurs, the intestinal absorption of copper is blocked. PMID- 3335325 TI - Altered cell kinetics in the large bowel. PMID- 3335326 TI - Sclerosing cholangitis in childhood. PMID- 3335327 TI - Treatment of tense ascites. PMID- 3335328 TI - Lymphoma in the mesenteric lymph node cavitation syndrome. PMID- 3335329 TI - Oral nifedipine in the treatment of noncardiac chest pain. PMID- 3335330 TI - Chylomicron retention disease. PMID- 3335331 TI - Fibronectin concentration in ascites does not differentiate between malignant and nonmalignant ascites. PMID- 3335332 TI - HLA-DA expression in children with celiac disease. PMID- 3335333 TI - Predicting relapse in asymptomatic Crohn's disease patients. PMID- 3335334 TI - Quinolones: careful use will preserve their value. PMID- 3335335 TI - Atypical presentations of neurological illness in the elderly. AB - The vicissitudes of aging make diagnosis of neurological disorders in the elderly especially challenging. The manifestations of neurological disease are often varied and confusing, and also may be misleading, since they may indicate a non neurological condition. The atypical clinical manifestations of several age prevalent neurological disorders are reviewed, along with appropriate diagnostic strategies. PMID- 3335336 TI - Quinolones: their uses in geriatric infections. AB - The quinolones represent a unique class of drugs which offer a new option for clinicians to treat a wide variety of infections in the elderly patient. Whereas the emergence of resistance is a major problem with the older quinolones such as nalidixic acid, this appears to be a minor problem with the new fluoroquinolones such as norfloxacin or ciprofloxacin. These drugs are bactericidal and are well absorbed orally. Parenteral preparations should be available in the future. The drugs are particularly active against gram-negative bacilli, including Pseudomonas aeruginosa. The fluoroquinolones are less active against pneumococci, Group A streptococci, Pseudomonas cepacia, and most anaerobes. The drugs appear potentially useful to treat urinary tract infections caused by multiply resistant pathogens, prostatitis, gastrointestinal pathogens, osteomyelitis, gram-negative pneumonia, and sexually transmitted diseases. Adverse effects occur in approximately 10% of patients and include gastrointestinal symptoms and potential central nervous system toxicity in patients receiving theophylline, non-steroidal drugs, or caffeine. The oral quinolones may reduce the costs of treating serious infections in the elderly. PMID- 3335337 TI - Hip pain in the elderly: evaluation and diagnosis. AB - Hip pain in the elderly can result in severe disability with compromise of independence. The causes of hip pain include many intrinsic and extrinsic disorders. Evaluation of the geriatric patient with pain in the vicinity of the hip requires a complete history and physical, radiographic evaluation and appropriate laboratory studies in order for proper management to be instituted. PMID- 3335338 TI - Malabsorption: common causes and their practical diagnosis. AB - Malabsorption may present as non-specific ill health and malnutrition in the elderly. Outside major medical centers, however, investigation is often thought to be difficult and unrewarding, and screening tests unreliable. Therefore, a direct approach is suggested to identify treatable small bowel disease in those elderly patients with a clinical possibility of malabsorption. It is based on the use of plain abdominal x-ray, endoscopy with duodenal biopsy, and small bowel meal. PMID- 3335339 TI - Swallowing disorders in the elderly: a guide to diagnosis and treatment. AB - Swallowing disorders are common in the elderly. They are most commonly seen in patients with cognitive-perceptual changes or neurologic deficits. The history and physical exam may be useful to increase your index of suspicion but cannot determine if a patient is at risk for aspiration. The modified barium swallow using videofluoroscopy is the most useful modality we have at this time for diagnosing swallowing disorders and determining appropriate interventions. Frequently, swallowing problems can be addressed with changes in dietary consistencies, by changes in positioning, or by techniques to improve oral control and sensitivity to food in the mouth. PMID- 3335340 TI - Tax exemption under attack as deficits rise. PMID- 3335341 TI - Economists see closures, cost cuts ahead. PMID- 3335343 TI - Consumers rate health care advertising. PMID- 3335342 TI - Experiment: hospitals at risk for quality. PMID- 3335344 TI - 1988: lean year for some, leaner for others. PMID- 3335345 TI - Ellwood: still a true believer in HMOs, competition. Interview by Maria R. Traska. PMID- 3335346 TI - Diversification: more black ink than red ink. PMID- 3335348 TI - Computers communicate with voice/data links. PMID- 3335350 TI - AHA integrates societies. PMID- 3335349 TI - Making friends with MDs via telecommunications. PMID- 3335347 TI - Hospital liable for negligence of ED physician. PMID- 3335351 TI - Computers speak, money talks, hospitals listen. PMID- 3335352 TI - A word of caution about unrelated business income. Interview by Bob Uhlar. PMID- 3335353 TI - Satellite use soars. PMID- 3335354 TI - Get the facts on fax before you purchase. PMID- 3335355 TI - Business set for second attack on health costs. PMID- 3335357 TI - Physicians' roles will keep changing in 1988. PMID- 3335356 TI - Efficiency to occupy the bottom line in 1988. PMID- 3335358 TI - Shrinking profits, tax-exemption fights ahead. PMID- 3335359 TI - Economic concerns to drive productivity. PMID- 3335360 TI - AIDS: explosive growth in public awareness. PMID- 3335361 TI - Definition of infectious waste broadened. PMID- 3335362 TI - New construction projects cited in report. PMID- 3335363 TI - District hospitals consider bed tax to finance indigent care. PMID- 3335364 TI - CFOs' focus the same despite changing times. PMID- 3335365 TI - Tax issues could plague not-for-profits. PMID- 3335366 TI - Market crash, tax reform will affect premiums. PMID- 3335367 TI - Physician marketing budgets to grow in '88. PMID- 3335368 TI - Sales: will it attain dignity in hospitals? PMID- 3335369 TI - Plan designs change to fit choice and cost. PMID- 3335370 TI - Will operating margins limit access to capital? PMID- 3335371 TI - Last challenge to California tort reform law? PMID- 3335372 TI - Labor and management strive to control costs. PMID- 3335373 TI - Cost-sharing increases for employees. PMID- 3335374 TI - AMA addresses medical staff self-governance. PMID- 3335375 TI - States adopt risk-management regs. PMID- 3335376 TI - Taylor: tax exemptions v. charitable spirit. Interview by Emily Friedman. PMID- 3335377 TI - What will imaging mergers mean to hospitals? PMID- 3335378 TI - Can lasers cut hospital costs? PMID- 3335380 TI - R&D to become "research and improvement". PMID- 3335379 TI - HealthWest manages managed care contracts. PMID- 3335381 TI - Quality and outcome are '88 research focus. PMID- 3335382 TI - Software, staff dominate '88 hospital budgets. PMID- 3335383 TI - Replacing aging info systems tops priorities. PMID- 3335384 TI - Active coronaries, large and small. PMID- 3335385 TI - Perinatal pulmonary hyperplasia due to laryngeal atresia. AB - A premature newborn boy, who died at birth because of cartilaginous laryngeal atresia, showed lung development that was far more advanced than normal for gestational age. The lungs, which were histologically normal, were three times the expected weight and showed a degree of alveolarization appropriate for 3 months' postnatal age. The lungs crowded the chest cavity so that the diaphragm was flattened and immobilized; the massive ascites, documented by ultrasound 5 weeks prior to delivery, appeared to be due to obstructed venous return. Thus, the pulmonary hyperplasia, a new finding in perinatal pathology, caused severe fetal ascites. Subsequently, the hyperplasia led to acute polyhydramnios that, ultrasonographically, was observed to develop 2 weeks prior to delivery. The observation that fetal lungs may be hyperplastic has a bearing on the known relationship between fetal lung growth and retention of lung fluid. PMID- 3335387 TI - A uniform histopathologic grading system for prostate cancer. Subcommittee on Diagnostic Nomenclature, Prostate Cancer Working Group, Organ Systems Program. PMID- 3335386 TI - Fat embolism to the cardiac conduction system associated with sudden death. AB - During a brief hospital stay, a patient under treatment with corticosteroids for lymphoma died suddenly and unexpectedly. At autopsy, fat emboli were identified in the lungs, myocardium, liver, and brain. Examination of the cardiac conduction system revealed fat emboli in the vessels of the bundle of His as well as those accompanying the bundle branches, a finding believed to have resulted in the sudden death. This report is the first of fat embolization to the cardiac conduction system and emphasizes the importance of examination of this system in cases of unexplained or sudden death. PMID- 3335388 TI - Is there a simultaneous involvement of membranous and IgA nephropathy in hepatitis B antigenemia? PMID- 3335389 TI - Apocrine cystic metaplasia and cancer risk. PMID- 3335390 TI - Importance of diet and nutrition in evaluating the safety of drugs. PMID- 3335391 TI - Distribution of disease at autopsy in 100 women with ovarian cancer. AB - Clinical and morphologic factors that affected the distribution of disease are described in 100 cases of ovarian cancer at autopsy. In addition to the expected pattern of pelvic and abdominal peritoneal spread, extensive visceral parenchymal metastases were seen: liver parenchyma (45%), lung parenchyma (39%), small and large intestinal wall (52% and 55%), lymph nodes (70%), pancreas (21%), ureter (24%), bone (11%), and brain (6%). Liver parenchymal metastases replaced more than one third of the liver in 25% of cases, whereas lung metastases always involved less than one third of the lungs. When intestinal wall invasion was seen, bowel obstruction was present more often (71%) than when only intestinal serosa was involved (30%). Lymphatic invasion was predictive of lymph node, small intestinal wall, pancreatic, and liver as well as lung parenchymal metastases. Blood vessel invasion was predictive of pancreatic and ureteral metastases. Clinical stage I at diagnosis was associated with high incidences of liver parenchymal (56%), lymph node (56%), lung parenchymal (44%), large intestinal wall (33%), and bone (33%) metastases. Thus, ovarian cancer has parenchymal metastases similar to other carcinomas in addition to its peritoneal spread. Lymphatic and blood vessel invasion is predictive of such involvement. Intestinal wall invasion predicts bowel obstruction. PMID- 3335392 TI - A test for detection of colorectal cancer. PMID- 3335393 TI - Clinical choroidal thrombosis, hypertension, and diabetes mellitus: an electron microscopic study. AB - Changes in the choroidal artery were examined at autopsy in 16 Japanese patients with hypertension and insulin-dependent diabetes mellitus. These changes could be divided into 1) arteriosclerotic ones consisting of intimal thickening due to migration of smooth muscle cells, 2) hyaline deposits in the subendothelium, 3) extensive degeneration (moth-eaten atrophy and necrosis) of medial smooth muscle cells, and 4) changes resulting from fibrinoplatelet thrombi and their organization (recanalization and obstruction). The intimal thickening and medial damage correlated with aging, were accelerated by hypertension, and were remarkable in arterioles less than 60 micron in diameter. Diabetes mellitus apparently did not enhance these vascular changes. Thrombotic occlusion or narrowing of the choroidal artery was frequently observed in the arterioles of patients with hypertension and diabetes mellitus who had chronic azotemia or renal insufficiency. Subendothelial hyaline deposits were increased in patients with diabetes. The narrowing or obstructive changes in the choroidal artery were extensive in the intraocular blood vessels. These changes may be secondary and induce damage to other intraocular blood vessels and tissues, including the retina. PMID- 3335394 TI - Biochemical confirmation of recombination within the B-G subregion of the chicken major histocompatibility complex. AB - Analysis of the B-G antigens of eight chicken major histocompatibility complex (B) system recombinant haplotypes by high resolution two-dimensional gel electrophoresis has provided evidence for the transfer of the complete B-G subregion in seven cases. In the eighth, a partial duplication within the B-G subregion appears to have occurred. In this recombinant, the entire array of polypeptides associated with one parental allele, B-G23, is expressed together with nearly the entire array of B-G polypeptides of the other parental haplotype, B2. This compound polypeptide pattern corroborates the serological evidence for a partial duplication within the B-G subregion and provides indirect evidence for the existence of multiple loci within B-G and for a means by which polymorphism may be introduced into the chicken major histocompatibility complex. PMID- 3335395 TI - An immunochemical analysis of class I (BoLA) molecules on the surface of bovine cells. PMID- 3335396 TI - The nucleotide sequence of the H-2K gene of C3Hf/HeN mice. PMID- 3335397 TI - Sequence of the mouse Q4 class I gene and characterization of the gene product. AB - The Q4 class I gene has been shown to participate in gene conversion events within the mouse major histocompatibility complex. Its complete genomic nucleotide sequence has been determined. The 5' half of Q4 resembles H-2 genes more strongly than other Q genes. Its 3' end, in contrast, is Q-like and contains a translational stop signal in exon 5 which predicts a polypeptide with an incomplete membrane spanning segment. The presence of two inverted B1 repeats suggests that part of the Q4 gene may be mobile within the genome. Gene transfer experiments have shown that the Q4 gene encodes a beta 2-microglobulin associated polypeptide of Mr 41,000. A similar protein was found in activated mouse spleen cells. The Q4 polypeptide was found to be secreted both by spleen cells and by transfected fibroblasts and was not detectable on the cell surface. Antibody binding and two-dimensional gel electrophoresis indicate that the Q4 molecule is identical to a mouse class I polypeptide, Qb-1, which has been previously described. PMID- 3335398 TI - Analysis of cross-protection between serotypes and passively transferred immune globulin in experimental nutritionally variant streptococcal endocarditis. AB - Nutritionally variant streptococci (NVS), which account for 5 to 10% of all cases of streptococcal endocarditis, were recently subdivided into three serotypes. In the past, using a rabbit endocarditis model, I demonstrated that by immunization of rabbits with NVS and by challenge with a strain from the homologous serotype a level of 90 to 100% protection was elicited. In the present study, the level of cross-protection between strains from different serotypes was measured. No cross protection was demonstrated between serotype I and II or III strains. However, significant cross-protection was observed when serotype II and III strains were analyzed in the model. Since high levels of immunoglobulin G were demonstrated against the surface of the NVS after immunization, passive transfer experiments were initiated. Even at comparable levels of surface immunoglobulin G, none of the rabbits given immune globulin were protected against challenge with a dose of live NVS that equaled 20 times the 50% infective dose. Therefore, it appears that components from the immune system, in addition to humoral components, are required for active protection against NVS endocarditis. PMID- 3335399 TI - Immunosuppressive properties of Actinobacillus actinomycetemcomitans leukotoxin. AB - Actinobacillus actinomycetemcomitans produces a leukotoxin that kills human polymorphonuclear cells (PMNs) and monocytes but not lymphocytes. In this study, we examined A. actinomycetemcomitans leukotoxin for its ability to alter human peripheral blood lymphocyte (HPBL) responsiveness. After a 90-min exposure to the leukotoxin, all monocytes were killed and HPBL responsiveness to mitogens and antigens was significantly inhibited. The ability of the leukotoxin to inhibit HPBL responses was not surprising, since monocytes and macrophages are required for many lymphocyte functions. However, we were unable to totally restore HPBL responsiveness when adherent autologous monocytes were added back to cultures of leukotoxin-treated lymphocytes. These studies demonstrate that A. actinomycetemcomitans leukotoxin may also exert nonlethal effects directly on lymphocytes. Furthermore, impaired lymphocyte function did not appear to be the result of indirect effects of products released by dying monocytes. Although it is not clear how A. actinomycetemcomitans acts to cause disease, several investigators have proposed that impaired host defenses may play a pivotal role. Several studies have demonstrated defects in PMN, monocyte, and lymphocyte function in patients with periodontal disease. These findings, along with the data presented in this paper, support the hypothesis that patients who harbor A. actinomycetemcomitans could suffer from local or systemic immune suppression. The effects of this suppression may be to enhance the pathogenicity of A. actinomycetemcomitans itself or that of some other opportunistic organism. PMID- 3335400 TI - Induction and expression of cell-mediated immune responses in inbred mice infected with Coccidioides immitis. AB - Comparisons of the course of coccidioidomycosis in two strains of inbred mice established that BALB/c mice are significantly more susceptible to pulmonary infection with Coccidioides immitis than are DBA/2 mice. The susceptibility of BALB/c mice does not reside in their inability to mount a delayed-type hypersensitivity response to C. immitis antigen. That is, BALB/c mice manifested footpad hypersensitivity to coccidioidin early during the course of disease, to a level comparable to that of DBA/2 mice. In contrast to the more resistant DBA/2 mouse strain, however, BALB/c mice developed anergy by day 15 postinfection. Suppression of the delayed-type hypersensitivity response was not specific for C. immitis antigen, as evidenced by the finding that BALB/c mice immunized with mycobacterial purified protein derivative prior to infection with C. immitis were suppressed in their footpad response to mycobacterial antigen at day 15 postinfection. Taken together, these results establish that genetically determined susceptibility to this fungus is associated with an acquired suppression of cell-mediated immune reactivity. PMID- 3335401 TI - Reduced oxidative function in gingival crevicular neutrophils in periodontal disease. AB - Measurable amounts of viable and functional polymorphonuclear neutrophils (PMNs) are recovered from pooled washings of the gingival crevice of healthy individuals. In the present study, we have assessed the ability of the PMNs removed from single healthy or diseased pocket sites to mount an oxidative burst when challenged with phorbol myristate acetate (PMA) and compared these activities with each other and with those obtained with autologous peripheral blood PMNs. The oxidative burst after PMA stimulation was evaluated by using methods developed for the flow cytometer. The results showed that the PMNs collected from untreated disease sites were minimally responsive to PMA when compared with peripheral-blood PMNs collected at the same time from the same individual. Thus, whereas the peripheral-blood PMNs exhibited significantly lower resting oxidative product formation and a 500% increase when stimulated with PMA, all gingival-crevicular PMNs exhibited significantly higher resting formation of oxidized products but only a 150% increase after PMA stimulation. PMNs obtained from a consistently healthy site had significantly higher resting production of oxidized products and were able to mount the greatest absolute increase in oxidized products after PMA stimulation when compared with PMNs collected from diseases sites. Mechanical debridement of these diseased sites, which both reduced the bacterial numbers and restored clinical health, resulted in the recovery of gingival-crevicular PMNs that exhibited an oxidative burst more typical of that observed in PMNs obtained from healthy gingival sites and from the peripheral blood. This suggested that the PMNs collected from the diseased sites either had been exhausted by the large numbers of bacteria present in these sites or had been specifically inhibited by these bacteria. PMID- 3335403 TI - Adherence of Pasteurella multocida or Bordetella bronchiseptica to the swine nasal epithelial cell in vitro. AB - The interaction of Bordetella bronchiseptica or Pasteurella multocida with swine nasal epithelial cells was studied in vitro. The mean number of B. bronchiseptica organisms adhered per cell was about three times as high as that of P. multocida (P less than 0.01), and the adherence was specifically inhibited by the homologous antiserum prepared with the whole-cell antigen of each bacterium. The poor affinity of P. multocida to the swine nasal mucosa as compared with that of B. bronchiseptica was also demonstrated in the cultured fragments of the nasal mucosa. When observed with a scanning electron microscope, B. bronchiseptica organisms colonized the fragments, whereas few P. multocida organisms adhered. Morphologically, the P. multocida-infected fragments had an essentially normal structure, whereas marked degeneration and marked desquamation of the epithelial cells and severe inflammatory reactions were observed in many areas of the B. bronchiseptica-infected fragments. These morphological observations were consistent with those for the nasal mucosa of P. multocida- or B. bronchiseptica infected neonatal pigs (T. Nakai, K. Kume, H. Yoshikawa, T. Oyamada, and T. Yoshikawa, Jpn. J. Vet. Sci. 48:693-701, 1986; T. Oyamada, T. Yoshikawa, H. Yoshikawa, M. Shimizu, T. Nakai, and K. Kume, Jpn. J. Vet. Sci. 48:377-387, 1986). Cultured swine nasal fragments, however, were equally injured when they were incubated in a medium containing purified dermonecrotic toxin (DNT) preparations of B. bronchiseptica or P. multocida. Therefore, these DNT preparations can induce morphological damage closely resembling that induced in vivo. Hence, colonization of B. bronchiseptica and production of its DNT on the swine nasal mucosa appear to result in the production of mucosal damage. On the other hand, P. multocida seems to lack the ability to colonize normal swine nasal mucosa, thus resulting in no production or the slight production of DNT to such an extent as to produce mucosal damage. The present data support our previous hypothesis (Nakai et al.; Oyamada et al.) that B. bronchiseptica induces swine atrophic rhinitis, whereas P. multocida does not. PMID- 3335402 TI - Volunteer studies of deletion mutants of Vibrio cholerae O1 prepared by recombinant techniques. AB - Vibrio cholerae O1 A-B- vaccine strain JBK 70 and A-B+ CVD 101 prepared by recombinant DNA techniques from pathogenic EI Tor Inaba N16961 and classical Ogawa 395, respectively, were fed to 38 volunteers in single doses of 10(4) to 10(10). Although severe diarrhea did not occur in any vaccine, more than one-half developed mild diarrhea. These attenuated strains colonized well and elicited prominent vibriocidal and antitoxic (CVD 101) antibody responses. Recipients of a single dose of JBK 70 were significantly protected when challenged with 10(6) wild-type N16961. Diarrhea occurred in 7 of 8 controls but in only 1 of 10 vaccines (P less than 0.003, 89% vaccine efficacy), demonstrating the potency of immune mechanisms that do not involve cholera antitoxin. Further derivatives were prepared to explore the pathogenesis of the residual diarrhea, considering that either intestinal colonization by the vaccine itself or accessory toxins might be responsible. CVD 102, an auxotrophic mutant of CVD 101, did not cause diarrhea but colonized poorly and elicited feeble immune responses. Derivatives of JBK 70 and CVD 101 (CVD 104 and 105) deleted of genes encoding the EI Tor hemolysin still caused mild diarrhea. Genetically engineered strains can be colonizing, highly immunogenic, and protective single-dose oral vaccines, but they must be further attenuated before they can be considered for use as public health tools. PMID- 3335404 TI - Murine major histocompatibility complex and immune response to Eimeria falciformis. AB - The genetics of the immune response to Eimeria falciformis were investigated in three inbred and six congenic strains of mice. There were significant differences among strains in oocyst production and age-related mortality from parasitic infection. Genes within the H-2 complex and also non-H-2 genes share in the immune response to eimerian infection. PMID- 3335405 TI - Ability of Vibrio vulnificus to obtain iron from hemoglobin-haptoglobin complexes. AB - It has been suggested that the normal serum protein, haptoglobin (Hp), serves a bacteriostatic role by binding free hemoglobin (Hm), thus making heme iron unavailable for bacterial growth. Previous studies showed that, unlike Escherichia coli, Vibrio vulnificus was able to overcome this Hp-blocking effect. We report here a study on the iron-withholding property of the three major human Hp phenotypes, Hp 1, 2, and 2-1. Results of experiments with human serum showed that V. vulnificus C7184 was able to obtain iron from Hm bound to Hp types 1 and 2, but not that bound to Hp 2-1. E. coli 2395-80, on the other hand, was unable to overcome the blocking effect of any Hp phenotype. Using purified Hp 1, we also demonstrated that, although V. vulnificus was unable to grow in a deferrated medium without an additional iron source, it was able to grow with the addition of the Hm-Hp complex. PMID- 3335406 TI - Evidence for the phagocytic transport of intestinal particles in dogs and rats. AB - Fluorescent latex beads of two different colors were implanted into separate intestinal segments in individual dogs and rats. Mesenteric lymph node phagocytes subsequently contained multiple beads of one or the other color but rarely both colors, indicating that intestinal phagocytes transported the latex beads to the draining lymph node. Fluorescent labeled Escherichia coli was implanted into rat ligated intestinal segments, and rare mesenteric lymph node phagocytes subsequently contained fluorescent bacteria, suggesting that intestinal bacteria might be transported in the same manner as inert latex beads. PMID- 3335407 TI - Fungal-strain-dependent alterations in the time course and mortality of chronic murine pulmonary blastomycosis. AB - Intratracheal injection of 10(4) conidia of Blastomyces dermatitidis strain M1-A into mice was shown in previous work to induce chronic pulmonary and disseminated infection with histopathologic features of chronic human blastomycosis. Furthermore, 10-fold variations in inoculum density produced marked changes in mean survival times (MSTs), i.e., 32 days at 10(6), 36 days at 10(5), 97 days at 10(4), and 172 days at 10(3). A second strain (M1-B) failed to induce death in this model. To assess fungal-strain-dependent virulence, we extended these previous studies to 11 additional human isolates. Groups of male BALB/cByJ mice (6 to 8 weeks old) were injected intratracheally with 10(4) conidia from each of the 13 strains; the mice were weighed weekly and monitored for mortality, and their lungs were examined histopathologically. Infection rate and mortality were 100% in all groups except for the M1-B inoculated mice. For strains M1-B and M1 A, MST and mortality curves were not significantly different from those observed in our previously reported experiments. Four different survival patterns were noted in infected mice. The shortest MSTs were produced by strains M2-E, M2-B, M2 K, M2-H, and M2-A (24, 26, 26, 27, and 31 days, respectively), and the longest MST was seen in animal groups inoculated with strains M2-J and M2-G (130 and 134 days, respectively). Strains M2-I, M2-F, and M2-D produced intermediate MSTs of 65, 79, and 80 days, respectively. The 107-day MST induced by M1-A did not differ from strain M2-C-induced MST but differed significantly from the MST produced by the other strains. Pulmonary histopathology was similar in all animals dying with blastomycosis. The wide spectrum in survival times was not related to differences in clinical status of the patient from whom the isolate had been obtained, to fungal inoculum viability, or to individual mouse weight at inoculation. Strain dependent virulence factors present in these fungal isolates alter the disease course in inbred mice in a fashion similar to that induced by 10-fold inoculum variation of strain M1-A conidia. These 13 isolates of B. dermatitidis, 1 avirulent and 12 with differing levels of virulence, provide tools for future studies into the nature of fungal virulence determinants in chronic blastomycosis. PMID- 3335408 TI - Lipopolysaccharide phase variation determines the complement-mediated serum susceptibility of Coxiella burnetii. AB - Phase variation of Coxiella burnetii is due to variation of the lipopolysaccharide (LPS), a phenomenon analogous to smooth-to-rough LPS variation of gram-negative enteric bacteria. Virulent enterobacteria usually have a smooth LPS and resist serum killing, whereas avirulent rough LPS mutants are sensitive to complement-mediated serum killing. Like gram-negative enterobacteria, smooth LPS phase variants of C. burnetii are virulent, whereas the rough LPS variants are avirulent. We therefore studied the effects of human serum on the LPS variants of the Nine Mile strain of C. burnetii. Analogous to gram-negative enterobacteria, the smooth and intermediate LPS C. burnetii phase variants were resistant to complement-mediated serum killing, whereas the rough LPS variants were killed by serum complement. Although the smooth and intermediate LPS variants were serum resistant, they differed in their interactions with the complement system. The smooth LPS variant activated complement poorly and did not bind C3b; however, the intermediate LPS variant activated complement and bound C3b. The rough LPS variant activated complement via the alternative pathway, whereas the intermediate LPS variant activated the classical pathway. These results provide an explanation for the avirulent nature of the rough LPS variant of C. burnetii and suggest that differences in C. burnetii LPS structure influence the interactions of the LPS phase variants with the complement system. PMID- 3335410 TI - Streptococcus sanguis surface antigens and their interactions with saliva. AB - Saliva-binding molecules of Streptococcus sanguis and their receptors were investigated. Streptococcal cell surfaces were extracted with a barbital buffer and examined immunochemically. Strains G9B and Blackburn, which adhere specifically to saliva-coated hydroxyapatite via immunologically related adhesins, possess 80-, 62-, and 52-kilodalton (kDa), and 52-, 42-, and 29-kDa polypeptides, respectively, which correlate with adhesion to saliva-coated hydroxyapatite. Nonadherent strains Adh- and M-5 lack these antigens. In an immunoblot overlay, the putative adhesins bound to a 73-kDa receptor present in submandibular saliva but not in parotid saliva. G9B also contains a 160-kDa surface protein which bound to an unidentified receptor in both submandibular and parotid saliva samples. Blackburn barbital-extracted components bound to 78- and 70-kDa receptors in parotid saliva. These bacterial-salivary interactions may be important in the regulation of oral ecology. PMID- 3335409 TI - Use of lytic bacteriophage for Actinomyces viscosus T14V as a probe for cell surface components mediating intergeneric coaggregation. AB - A lytic bacteriophage for Actinomyces viscosus T14V (the reference strain for actinomyces coaggregation group A) was isolated from raw sewage. This phage, designated BF307, also lysed the T14V-derived nonfimbriated mutant PK455-2 as well as A. viscosus MG-1 and T14AV but not the other serotype 2 or serotype 1 strains of this species that were tested or any of nine Actinomyces naeslundii isolates. Phages BF307 belonged to Bradley morphological group C and was similar in appearance to the A. viscosus MG-1 phages Av-1 and Av-3, which do not productively infect A. viscosus T14V. A. viscosus MG-1 mutants selected for resistance to phage BF307, Av-3, or CT7 (a human dental plaque isolate with the same host range as BF307) were coresistant to the other two phages but sensitive to Av-1. These results indicate that the receptors on A. viscosus MG-1 for phages BF307, Av-3, and CT7 are identical or share a common precursor and that the receptor for phage Av-1 is distinct. Comparison of the genomes of BF307, Av-3, and CT7 revealed that their DNAs were similar in size but distinguishable by restriction analysis. Two altered coaggregation phenotypes were identified among the phage BF307-resistant mutants of strains MG-1, T14V, T14AV, and PK455-2. Class I mutants had lost the ability to interact with coaggregation group 1 streptococci, and class II mutants did not coaggregate with either group 1 or group 2 streptococci. These results are consistent with the proposal that the phage BF307 receptor on these A. viscosus strains is related to one of the structures that mediates coaggregation with oral streptococci. A model to delineate the various coaggregation mediators on the surface of actinomyces coaggregation group A cells is presented, and the use of these phages to probe surface components of human oral actinomyces strains is discussed. PMID- 3335411 TI - Prevention of peroral and congenital acquisition of Toxoplasma gondii by antibody and activated macrophages. AB - Intramuscular administration of Toxoplasma gondii lysate antigens to mice produced titers of T. gondii-specific antibody (measured by Sabin-Feldman dye test) greater than or equal to 1:1,024 in their sera. Intravenous administration of heat-killed Propionibacterium acnes to mice produced peritoneal macrophages with enhanced microbicidal capacity against T. gondii. Mice with high antibody titers or activated peritoneal macrophages or both had reduced numbers of Toxoplasma cysts in their brains 30 days after peroral challenge. Specific antibody and activated macrophages appeared to act together to significantly (P = 0.01) reduce the numbers of Toxoplasma cysts. A reduction in tissue infection as a result of these treatments was also demonstrated by subinoculation of brain tissue. A high antibody titer alone did not protect against congenital infection. Mice treated with P. acnes delivered reduced numbers of T. gondii-infected pups (P greater than 0.05). Treatment that produced high titers of Toxoplasma antibody and activated macrophages provided significant protection against congenital infection (P less than 0.05). PMID- 3335412 TI - A flagellar pocket membrane fraction from Trypanosoma brucei rhodesiense: immunogold localization and nonvariant immunoprotection. AB - In contrast to the abundance of detailed information on variant-specific surface coat antigens of African trypanosomes, data on possible common or nonvariant antigens within these protozoa are surprisingly limited. In this study, the cellular localization and protective potential of a previously characterized flagellar pocket membrane (FPM) fraction were determined. Immunogold staining of live trypanosome suspensions at 0 to 4 degrees C by using anti-FPM hyperimmune serum raised in rabbits as the primary antibody revealed specific staining of the parasite surface at the emergence of the flagellum from the flagellar pocket. The same specificity of immunogold localization was obtained for each of three distinct variable antigenic types (VATs) of a serodeme of Trypanosoma brucei rhodesiense Wellcome strain. Products of translated mRNA preparations from each of the VATs were precipitated by the FPM antiserum and revealed identical banding patterns when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. Immunization of mice with FPM fraction protected them against infection by two of the VATs; the third VAT was afforded poor protection. This is the first demonstration of the combined cellular localization, nonvariant nature, and protective potential of a membrane fraction from African trypanosomes. PMID- 3335414 TI - Antibody targeting to the murine lymphoma ESb-MP: increased accumulation due to reduced internalization into lymphoma cells as compared to normal lymphoid cells. AB - Using rat monoclonal antibody (MAb) 12-15A against the spontaneously metastasizing mouse lymphoma variant ESb-MP, we elaborated conditions for targeting. In vitro, high binding of labelled antibody to ESb-MP cells and low binding to lymphoid cells (e.g., spleen cells) was noted. In vivo, we observed pronounced accumulation in spleen, lymph nodes and bone marrow, the uptake kinetics indicating high accessibility of the target antigen in these tissues, and rapid clearance of radioactivity from blood and most normal tissues, indicating degradation of the antibody and excretion of the label. Binding to lymphoma tissue was slow but persistent, resulting in high tumor:tissue ratios only after 2-3 days. Biodistribution could be dramatically changed by pre treatment of animals with excess cold antibody, which reduced trapping of labelled antibody in normal lymphatic tissue, leading to prolonged persistence in the blood and preferential uptake into tumor tissue. Monovalent 12-15A fragments showed less pronounced binding to lymphatic tissue, while being rapidly cleared from the circulation by virtue of their inherent tendency to bind to kidney tissue. Tumor:tissue ratios up to 56:1 were obtained by a combination of pre treatment with unlabelled 12-15A IgG or Fab fragment, followed by injection of labelled fragment or IgG, respectively. This is interpreted on the basis of differences in the internalization and retention of antigen-antibody complexes. Pre-treatment obviously leads to a temporary blockade or removal of the target antigen, which is much more efficient with normal lymphoid cells than with tumor cells. Thus, it may become possible to target antibodies into the tumor despite concurrent antigen expression on normal tissue. PMID- 3335413 TI - Mucosal and systemic immunity to Campylobacter jejuni in rabbits after gastric inoculation. AB - The mucosal and systemic immune responses to Campylobacter jejuni were studied in rabbits receiving gastric inoculation with live organisms. A lavage procedure was used to facilitate repeated monitoring of the intestinal immune response to C. jejuni. Immunity to C. jejuni was determined by secondary challenge by using the removable intestinal tie adult rabbit diarrhea (RITARD) model and monitoring for resistance to colonization and bacteremia. Oral-gastric inoculation of normal rabbits produced a transient intestinal colonization without diarrhea. C. jejuni serotypes differed in their ability to colonize the intestines of rabbits and to stimulate primary intestinal and serum antibody responses. Animals previously colonized were resistant to recolonization and the development of bacteremia after homologous challenge by the RITARD procedure but were not resistant to heterologous challenges. Anticampylobacter intestinal and serum IgA titers before this secondary infection were the most reliable predictors of resistance to colonization and bacteremia. PMID- 3335415 TI - Resistance to growth of the Moloney lymphoma YAC in semi-syngeneic graft recipients. AB - The growth of the Moloney-virus-induced lymphoma YAC was examined in its strain of origin, A, as well as in 6 AF1 hybrids, ALF1, AB6F1, ACBF1, AABYF1, AACAF1 and AASWF1. "Hybrid resistance", i.e., lower frequency of incidence of tumor takes compared to simultaneous A controls, was observed in all of the tested hybrids. The results with the H-2-congeneic hybrids AABYF1, AACAF1 and AASWF1 indicated that H-2 heterozygosity in itself was sufficient to exhibit hybrid resistance against YAC grafts. The A strain and its H-2 congeneic AABYF1, AACAF1 and AASWF1 hybrids all had similarly low activity in NK assays. Thus, the elevated resistance detected in these H-2 congeneic hybrids did not correlate with NK activity. The rejection capacity of the ALF1, AB6F1 and ACBF1 hybrids correlated to their relatively higher NK activity, when compared to the NK low AABYF1, AACAF1 and AASWF1 hybrids. However, consideration of quantitative differences in between the hybrids which expressed elevated NK activity (i.e., ALF1, AB6F1 and ACBF1) shows that the rejection capacity did not correlate with NK status. The hybrid with the strongest NK effect (ACBF1) was the least resistant to YAC growth (27% palpable tumors), and the hybrid with the weakest NK effect (ALF1) was the most resistant to YAC growth (7.2% palpable tumors). PMID- 3335416 TI - Radioimmunotherapy of human colon carcinoma by 131I-labelled monoclonal anti-CEA antibodies in a nude mouse model. AB - A mixture of 3 MAbs directed against 3 different CEA epitopes was radiolabelled with 131I and used for the treatment of a human colon carcinoma transplanted s.c. into nude mice. Intact MAbs and F(ab')2 fragments were mixed because it had been shown by autoradiography that these 2 antibody forms can penetrate into different areas of the tumor nodule. Ten days after transplantation of colon tumor T380 a single dose of 600 microCi of 131I MAbs was injected i.v. The tumor grafts were well established (as evidenced by exponential growth in untreated mice) and their size continued to increase up to 6 days after radiolabelled antibody injection. Tumor shrinking was then observed lasting for 4-12 weeks. In a control group injected with 600 microCi of 131I coupled to irrelevant monoclonal IgG, tumor growth was delayed, but no regression was observed. Tumors of mice injected with the corresponding amount of unlabelled antibodies grew like those of untreated mice. Based on measurements of the effective whole-body half-life of injected 131I, the mean radiation dose received by the animals was calculated to be 382 rads for the antibody group and 478 rads for the normal IgG controls. The genetically immunodeficient animals exhibited no increase in mortality, and only limited bone-marrow toxicity was observed. Direct measurement of radioactivity in mice dissected 1, 3 and 7 days after 131I-MAb injection showed that 25, 7.2 and 2.2% of injected dose were recovered per gram of tumor, the mean radiation dose delivered to the tumor being thus more than 5,000 rads. These experiments show that therapeutic doses of radioactivity can be selectively directed to human colon carcinoma by i.v. injection of 131I-labelled anti-CEA MAbs. PMID- 3335417 TI - Adhesion characteristics of human melanoma cell lines of varying metastatic potential. AB - The adhesive behaviour of a series of human melanoma cell lines, of varying metastatic potential, to basement membrane and stromal components was investigated in vitro. Experimental metastatic propensity was assessed from the number of pulmonary nodules formed after i.v. injection of cells into BALB/c nude mice. All cell lines showed similar kinetics of attachment when tested on plastic, type-I collagen films, type-I collagen hydrated gels, fibronectin, laminin type-IV collagen substrates and bovine aortic endothelial monolayers. Fibronectin-coated plastic compared to plastic alone produced increased cell attachment and spreading to the same extent in all the cell lines. The melanoma lines attached preferentially to cryostat sections of lung compared to other organs reflecting the pattern of organ involvement of metastasis in vivo. However, no significant quantitative differences in attachment to lung sections were seen between melanoma variants of differing metastatic capacities. Cells labelled with [125I]iododeoxyuridine to determine their initial organ distribution following i.v. injection showed that tumour-cell arrest was not significantly changed enough to explain the differing metastatic capacities. Thus it appears that adhesive properties of these melanoma cells are not correlated with their capacity to form metastases in vivo. PMID- 3335419 TI - Trends in breast cancer incidence and mortality in Denmark, 1943-1982. AB - The trend in breast cancer incidence and mortality was examined using data from the Danish Cancer Registry and the national mortality statistics respectively. The study population comprised 65,870 incident cases and 33,817 deaths from breast cancer in Denmark between 1943 and 1982. The incidence rate remained almost constant up to around 1960, whereafter it rose steadily. Comparatively little change was observed in mortality. Possible explanations for the differing trends in incidence and mortality include under-reporting of breast cancer from death certificates and improvement in survival. A multivariate statistical analysis showed that the increase in incidence was due mostly to a cohort effect, though calendar time may have had a slight effect as well. PMID- 3335418 TI - Correlation patterns of cancer relative frequencies with some socioeconomic and demographic indicators in Brazil: an ecologic study. AB - Sex-specific relative frequencies (RF) of oral, esophageal, stomach, colon, rectal, laryngeal, lung, female breast, cervical and penile cancers obtained from a government-sponsored, nation-wide data base of histopathological diagnoses were evaluated with respect to all possible inter-site correlations and with 12 socioeconomic and demographic variables for 23 States in Brazil. Use of bivariate and multivariate methods detected a high positive intercorrelation among RFs of lung, laryngeal and colon cancers regardless of sex. RFs for these 3 sites were also positively correlated with many markers of State development and affluence. Cervical and penile cancers emerged as a distinct subset with respect to their correlation patterns. RFs for these neoplasms were highly (positively) correlated (r = 0.8606, p less than 0.001) with each other and exhibited intense negative associations with many of the affluence markers and the former cancer sites. Bivariate correlations generally exhibited a better fit with female-specific RFs than with data from males which was reflected in the number of strong correlations detected by sex. PMID- 3335420 TI - An immunohistochemical study of laminin, type-IV collagen and type-III pN collagen with relation to reticular fibres in Hodgkin's disease. AB - The distribution of aminoterminal propeptides of type-III procollagen (indicating the presence of type-III pN-collagen, i.e., type-III collagen molecule with a non cleaved aminoterminal propeptide), laminin and type-IV collagen was studied by immunohistochemical methods. The results were compared with the distribution of reticular fibres using Gomori's reticulin stain. Lymph nodes from 20 cases of Hodgkin's disease (HD) and 3 spleens affected by nodular sclerosis HD were studied. The reticular fibres stained for all the antigens investigated, the strongest reaction being for pN type-III collagen. Thick fibres stained mainly for type-III pN-collagen, the BM proteins being located in a fragmented rim on the surface. The distribution and composition of fibres was similar in both nodal and extranodal infiltrations. The morphological alterations noted in the fibres comprised (1) compression between nodules in the nodular type of lymphocyte predominant HD, and (2) fragmentation, present in collections of histiocytes in lymphocyte-predominant HD. BM proteins and type-III pN-collagen were present in the walls of the sinuses and vessels. The marginal sinuses were often partially spared in spite of extracapsular invasion. Our results suggest that laminin, type IV collagen and type-III pN-collagen are important components of reticular fibres in HD and that the composition of the fibres is similar to that seen in the normal lymph node. PMID- 3335421 TI - Establishment and characterization of a new human bladder cancer cell line showing features of squamous and glandular differentiation. AB - Tumour-cell heterogeneity has been studied in a continuous cell line, UCRU-BL 17CL, established from a xenografted human primary bladder carcinoma. The cell line, grown in vitro for more than 30 generations, reflects the pathology of both the xenograft from which it was derived and the original human tumour. It comprises mainly adenocarcinoma cells which secrete mucin in vitro, as well as squamous and transitional carcinoma cells. Features of both adenocarcinomatous and squamous differentiation have been observed within the same cell. The line expresses ABH blood group isoantigens, binds to peanut lectin and reacts with monoclonal antibodies (MAbs) raised against keratin and against normal and malignant epithelial cells. It also reacts with MAbs against ras p21 proteins and the epidermal growth factor receptor (EGFR). It shows high levels of lactic acid dehydrogenase isozyme 5, consistent with a high-grade tumour, forms colonies in methylcellulose and is tumorigenic in nude mice. The karyotype (human) shows many marker chromosomes, consistent with expression of EGF receptors and ras p21 proteins, and an 11:13 translocation. DNA content, as studied by flow cytometry, reveals a shift from tetraploid to near triploid. This line may provide a useful model for studies of the histogenesis of bladder cancer and the relationship between transitional-cell carcinoma and the other histological subtypes of this disease. PMID- 3335422 TI - Metastasis of a human melanoma cell line in the nude mouse. AB - A human melanoma cell line has been established which when inoculated subcutaneously into nude mice, is consistently metastatic. In order to document blood-borne spread, it was necessary to excise the primary tumour so prolonging the life of the animal and allowing metastases to become apparent. Macroscopically detectable metastatic spread at autopsy was reliably indicated by weight loss of the animals. Metastases were widespread and involved the lungs, abdominal cavity and organs and the gonads. The size of the primary tumour at the time of its removal, and not the period of s.c. growth, determined the incidence of metastatic disease. Removal of tumours weighing less than 0.6 g prevented metastasis, whereas all of the animals showed widely disseminated disease if the tumour was allowed to attain a size of 1.6 g before excision. PMID- 3335423 TI - Presence of Langerhans cells in the cornea of Klebsiella keratoconjunctivitis mice. AB - Frozen sections of normal Balb/c corneas and corneas from Balb/c mice with Klebsiella keratoconjunctivitis were examined for the expression of class I, class II H-2 antigens and MAC-1 antigens using monoclonal antibodies in an immunoperoxidase technique. Class I antigens were readily detected, in both normal and diseased corneas, mainly in the epithelium. Class II (Ia) and MAC-1 antigens were not detected in the normal corneas. However, these two antigens were found mainly in the epithelium and to a lesser extent in the stroma of corneas from keratoconjunctivitis mice. Both normal and diseased corneas were furthermore shown to be peroxidase-. Since Langerhans cells (LC) are Ia+, MAC-1+, and peroxidase- cells, we conclude that although the normal mouse cornea is devoid of these cells, under bacterial infection LC infiltrate the corneal epithelium. PMID- 3335424 TI - The effects of D-penicillamine and daunorubicin on conjunctival fibroblast proliferation and collagen synthesis. AB - Two drugs, D-penicillamine and daunorubicin, were tested for their effect on proliferation and collagen synthesis of cultured conjunctival fibroblasts. This cell type is likely responsible for scar formation and ultimate filter surgery failure in glaucoma patients. Both drugs were antiproliferative; however, D penicillamine required 2000 times the concentration of daunorubicin to achieve a similar degree of inhibition. D-penicillamine had a more consistent effect on intracellular collagen synthesis than daunorubicin at the doses tested. In contrast, at concentrations of daunorubicin where all proliferation ceased, intracellular production and extracellular transport of collagen were maintained. PMID- 3335426 TI - Effect of cold air on aqueous humor dynamics in humans. AB - Several parameters of aqueous humor dynamics were measured in 11 human subjects before and after exposure of one eye to a continuous stream of cold air. In the treated eye, I.O.P. was found to decrease significantly from a mean +/- SD pre treatment value of 14.1 +/- 2.3 mmHg to a post-treatment value of 12.6 +/- 2.6 mmHg. Episcleral venous pressure was found to decrease significantly from a pre treatment value of 6.2 +/- 1.3 mm Hg. No significant changes were found in aqueous flow or total outflow facility, indicating that cold air exposure decreased I.O.P. by causing a decrease in episcleral venous pressure. PMID- 3335425 TI - A method of determining concentration of albumin in the living eye. AB - A noninvasive method of measuring the concentration of plasma protein in the anterior chamber is described. Fluorescein is applied to the cornea. After the aqueous humor becomes fluorescent, the polarization of fluorescence is measured. The concentration of plasma protein, mainly albumin, can be calculated from the polarization. PMID- 3335427 TI - Characterization of disulfide-linked crystallins associated with human cataractous lens membranes. AB - In order to characterize possible disulfide-linked interactions between lens fiber cell membranes and crystallins, two-dimensional diagonal electrophoresis has been used in combination with Western blot analysis. When these blots were probed with monospecific antisera against alpha, beta and gamma crystallins, membrane from five individual normal lenses showed no disulfide-bonded components. Membrane from 13 individual cataractous human lenses showed no disulfide-bonded alpha crystallin, but did show significant amounts of disulfide bonded beta crystallin in four out of the 13 lenses studied, and significant amounts of disulfide-bonded gamma crystallin in 10 out of the 13 lenses studied. Together, these studies demonstrate that intermolecular disulfide bonding of crystallins to purified fiber cell membranes is found only in cataractous lenses, and that the predominant polypeptide species involved in this interaction is gamma crystallin. PMID- 3335428 TI - Regional distribution of glutathione peroxidase and Glutathione-S-transferase in adult and premature human retinas. AB - The activities of glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GSH-S-tase) were investigated in adult and premature human retinas. The measurements were done in the vascular and avascular regions of premature retinas at gestational age of 22-33 weeks and in the central, mid-peripheral, and far peripheral regions of mature retinas from the age of 1 month to 73 years. Among the premature infants, those who survived for greater than 24 hours were supplemented with alpha-tocopherol (vitamin E) on a periodic basis. The vascular and avascular regions of premature retinas had higher activities of GSH-Px when compared to the central and far peripheral regions of mature retinas. Infants surviving more than 24 hr had higher activities of GSH-S-tase in the avascular region than infants who survived less than 24 hr. Survival did not affect either enzyme activity in the vascular regions. Mature retinas showed a decrease in GSH Px specific activity with age, but no age-related changes in GSH-S-tase were observed. These data demonstrate that premature infants are born with relatively high levels of GSH-Px and GSH-S-tase. PMID- 3335429 TI - The potential usefulness to research of retina obtained by biopsy. AB - Retinal biopsy has been performed on normal rabbits and dogs. It was shown that retinal samples could be obtained by internal and external routes in rabbits, but in dogs inability to achieve adequate vitrectomy precluded useful retinal biopsy by the internal route. A single external biopsy specimen of 3 mm diameter was more than adequate to undertake standard histopathological examination, immunocytochemical experiments and determination of cyclic nucleotide levels. The quality of the micrographs, immunocytochemical labelling of rhodopsin and phosphodiesterase, and cyclic nucleotide analyses were similar to those obtained with retinas from freshly enucleated eyes. The surgical exercise was well tolerated by most eyes and does not preclude serial biopsies being undertaken. It is concluded that retinal biopsy provides material of sufficient quantity and quality to satisfy many laboratory needs in retinal research. PMID- 3335430 TI - The regional distribution of vitamins E and C in mature and premature human retinas. AB - Vitamin E is used to ameliorate retinopathy of prematurity, but little is known about baseline vitamin E levels in retinas of premature infants or the effect of vitamin E supplementation on these levels. Vitamin E and C levels were measured in mature retinas (1 month to 73 years) and in retinas of premature infants (22 to 33 weeks of gestation). The infants fell into two groups: (1) those who survived less than 12 hr and received no vitamin E, and (2) those who survived greater than 4 days and received vitamin E supplementation. Premature infants are born with 5 to 12 percent the vitamin E levels found in mature retinas. Vitamin E levels in vascular and avascular retina of premature infants increased with gestation. Infants born greater than 27 weeks gestation and surviving at least 4 days with vitamin E supplementation demonstrated markedly elevated vitamin E levels in vascular and avascular retina when compared to supplemented infants less than 27 weeks gestation. Premature infants possessed 35-50% higher levels of retinal vitamin C than those found in mature retinas. These data demonstrate that premature infants are born with relatively low levels of retinal vitamin E, particularly in the avascular region, but contain an abundance of retinal vitamin C. These data further suggest that vitamin E supplementation results in a rapid increase in retinal vitamin E levels, particularly in infants greater than 27 weeks gestational age. PMID- 3335431 TI - Lighting conditions and retinal development in goldfish: photoreceptor number and structure. AB - The retinas of 63 goldfish were examined after varying durations of exposure to one of three environmental lighting conditions beginning before hatching: constant light (340 lux), cyclic light (12 hr 320 lux, 12 hr dark) and constant dark. Up to 8 months, no effects of constant light or dark on photoreceptor numbers or structure were apparent. Densities of rod and cone nuclei were normal and all retinal layers appeared normal by light microscopy. Exposure to constant light for 12 months or longer resulted in a reduction in rod density by 37%. Cone numbers were unaffected by constant light, even with exposures of 3 yr, and rod and cone outer segments were normal in length at 11-20 months under all environmental conditions. Due to poor survival, only one animal was available for quantitative examination from the group reared in constant dark 12 months or longer. Photoreceptor size and number in this retina were similar to those in the constant light condition. The results suggest that the formation and maturation of rods and cones in goldfish retina is unaffected by rearing in constant light. However, long-term exposure (greater than or equal to 12 months) may disrupt maintenance of differentiated rods. PMID- 3335433 TI - High visual contrast sensitivity in the young human infant. AB - The visual evoked potential (VEP) was used to estimate photopic contrast sensitivity of 10-week-old infants over a wide range of spatial frequencies including the acuity limit. Adult and infant VEP contrast sensitivity was compared for sinusoidal luminance gratings reversed in contrast at 6 Hz. Space average luminance was 220 cd/m2. Grating contrast was swept from well below the measured thresholds to well above them in 10 sec trials. Contrast thresholds were defined as the zero voltage intercept of the initial rising portion of the VEP amplitude versus contrast function. The VEP contrast sensitivity of 10-week-old infants was close to that of the adults for spatial frequencies below about 1 cycle (c)/deg. PMID- 3335432 TI - Lighting conditions and retinal development in goldfish: absolute visual sensitivity. AB - Goldfish (Carassius auratus) were reared from hatching in constant light (340 lux), cyclic light (12 hr 320 lux, 12 hr dark) or constant dark. Absolute visual threshold was determined psychophysically in animals that still responded to visual stimuli after 1-3 years of exposure, by means of a classically conditioned respiration suppression technique wherein animals were presented with different intensities of large diffuse flashes of monochromatic light. Fish reared in constant light and fish reared in cyclic light responded reliably to stimuli above threshold, but fish reared in constant light were on average 0.58 log unit less sensitive at 532 nm, near the peak of the rod action spectrum. Two of the four fish reared in darkness did not respond to the stimuli, and thus could not be conditioned, and another fish reared in darkness responded only occasionally; threshold could not be measured in these three fish. The one fish reared in darkness that responded consistently enough to be conditioned was more than 5 log units less sensitive than normally reared fish on the first day of testing, and became progressively less sensitive over the next 2 days. Rearing under constant dark or constant light had no obvious effect on spectral sensitivity at absolute threshold. The effect of rearing in constant light on absolute threshold correlates with morphological changes in rod density, but the effect of rearing in constant darkness does not. PMID- 3335434 TI - Central visual fields for short wavelength sensitive pathways in glaucoma and ocular hypertension. AB - While conventional clinical visual acuity and kinetic visual fields may be essentially normal in ocular hypertension and early stages of glaucoma, other foveal aspects of vision (eg color, spatial and temporal contrast sensitivity) may be quite abnormal. Specifically, a selective vulnerability of the short wavelength sensitive (SWS) visual pathways in these conditions has previously been noted. Here we studied the central visual fields of 33 primary open angle glaucoma (POAG) patients, 32 ocular hypertensives (OHT), and 24 age-matched normal controls using blue and yellow test flashes on bright yellow backgrounds. SWS cone and MWS and/or LWS cone pathway sensitivities were measured at the fovea and at 2.5 degrees, 5 degrees, 10 degrees and 15 degrees eccentricities, in either the inferior temporal (for OHT) or horizontal nasal retina (for POAG). As expected, all groups had normal sensitivity to yellow flashes--detected by LWS and/or MWS cones--in these meridians. By comparison, for the blue flashes- detected by the SWS cones--the POAG and OHT groups had sensitivity deficits, uniformly across the central visual field, of about 6X and 1.8X, respectively, compared to normals. While six of 31 (19%) OHT subjects had localized glaucomatous field defects (greater than 0.4 log units) in the non-foveal inferior temporal retina, none of the 12 OHT subjects who were also tested in the horizontal nasal retina showed loss in this meridian. Finally, while no POAG subjects had localized sensitivity loss for yellow flashes in the horizontal nasal retina, four did show local field defects with blue test flashes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335435 TI - Use of photographic techniques to grade nuclear cataracts. AB - Methods for objectively documenting and grading different varieties of lens opacities are needed in order to conduct research on risk factors for cataracts. This study tested the feasibility and reliability of using two different photographic methods to grade nuclear opacities. Photographs were taken of 41 eyes using a regular Topcon SL-5D photo slit lamp, and using a Topcon SL-45 (Scheimpflug) camera. The photographs were graded against a set of four standard photographs of increasing nuclear opacification. Densitometric analyses were also performed on both sets of photographs. The clinical grade, on examination, of the nucleus was compared to the examiner's grade of each photograph. Agreement was fair between the examination results and the grading of the photographs. Inter observer reliability was high (kappa = 0.71) with photographs taken using the photo slit lamp. Moreover, the severity grading of the photographs showed a good correlation with the severity of opacity as determined by densitometric analyses. On the basis of these data, and on the field experience, the use of photographs of the nucleus obtained by photo slit lamp may be used in epidemiological surveys. PMID- 3335436 TI - Human trabecular meshwork organ culture: morphology and glycosaminoglycan synthesis. AB - Human corneoscleral explants were maintained for several weeks in defined, serum free media. Trabecular cell vitality, as judged by vital stain exclusion, is high for at least one month. Trabecular ultrastructure, as compared to that of fresh eyes, first shows minor cellular and extracellular matrix degradation after 3 weeks in culture. The biosynthetic profiles of trabecular glycosaminoglycans (GAGs) change significantly by 3 weeks in culture. Eyes that are stored at 5 degrees C for up to 48 hr postmortem exhibit changes in trabecular ultrastructure and in GAG profiles; both characteristics return to normal by 7 days in culture. The incorporation pattern of 35S-sulfate and 3H-glucosamine into the GAGs of the trabecular meshwork (TM) is distinct from corneal or scleral incorporation. The relative incorporation of 3H-glucosamine into trabecular GAGs, as determined by sequential enzymatic degradation, is: 22.3% hyaluronic acid (HA), 27.9% chondroitin sulfate (CS), 21.3% dermatan sulfate (DS), 5.9% keratan sulfate (KS), 17.7% heparan sulfate (HS) and 4.9% unidentified material. The relative incorporation of 35S-sulfate into trabecular GAGs is: 0% HA, 32.9% CS, 34.8% DS, 7.7% KS, 13.8% HS and 11.1% into unidentified material. This profile is in good agreement with the profile that was previously obtained for human and nonhuman primate meshworks prior to culture. We conclude that corneoscleral explant organ culture is a useful tool for extracellular matrix studies within a time window from 7 to at least 14 days in culture. PMID- 3335437 TI - Mobile Pu in reservoir sediments of Nagasaki, Japan. PMID- 3335438 TI - Necessary update on U miners' 222Rn exposure. PMID- 3335440 TI - An electret passive environmental 222Rn monitor based on ionization measurement. AB - The electret passive environmental 222Rn monitor (E-PERM) is an extension of electret dosimeters used for measurement of x and gamma radiation. An E-PERM consists of a small cup or canister, having an electret at the bottom, and a filtered inlet at the top. The 222Rn gas entering through the filter and the decay products formed inside the cup generate ions which are collected by the electret. The reduction of charge (or surface potential) on the electret is a measure of time integrated 222Rn exposure. An E-PERM of 220-mL volume with an electret of 0.23 cm thickness gave a surface potential drop of 2.5 V for 37 Bq m 3 d (1 pCi L-1 d). The electret voltage was measured with a specially built surface potential voltmeter. This sensitivity was found adequate for a 1-wk measurement of 222Rn in homes. For longer term measurements, an E-PERM of 40-mL volume and an electret of 51-micron thickness was developed which gave a surface potential drop of 2.6 V for 37 Bq m-3 y (1 pCi L-1 y). Other combinations of chamber volume and electret thicknesses gave responses between these two values. The surface potential of electrets made from Teflon FEP were shown to stay stable even under extreme conditions of relative humidity. The ion collection process in E-PERMs was also shown to be independent of humidity down to an electret surface potential of 100 V. PMID- 3335441 TI - On the general validity of linear summation of dose equivalents for mixed radiations. AB - The current definition of dose equivalent for a mixture of radiations used in radiation protection implies some interaction between the radiations. This interaction cannot be derived from the existing biophysical models. A simple concept of interaction is introduced based on the postulate that in the chain of radiation inactivation events, there exists an intermediate stage where different initial lesions, produced by different radiations, become functionally indistinguishable. Hence, they are additive thereafter to produce the same end point observed. It can be shown that the definition of dose equivalent and the definition of average quality factors for mixed radiations can be derived from this concept. Furthermore, this simple concept can be shown to be consistent with many of the published experimental results in radiobiology using mixed radiations. The lesion additivity concept helps to provide both theoretical and experimental support for the otherwise arbitrary definitions of dose equivalent and average quality factor. PMID- 3335439 TI - Guidelines on limits of exposure to radiofrequency electromagnetic fields in the frequency range from 100 kHz to 300 GHz. International Non-Ionizing Radiation Committee of the International Radiation Protection Association. PMID- 3335442 TI - Dose rates to aquatic life near a U waste site. AB - Radiation dose rates to aquatic organisms have been estimated from radionuclide levels in fish, in water and in the sediments near an abandoned U waste site. The dose rates in the sediments were high (0.5 Gy y-1). Whitefish received dose rates of 10 mGy y-1 from internal 226Ra and could have received comparable external dose rates from the sediments when they forage near the lake bottom, as they usually do. The calculated dose rates to fish were comparable to those reported near an adjacent U mine (Sw83). PMID- 3335443 TI - A spreadsheet method for 90Sr and 89Sr interpretation. AB - A spreadsheet method of handling multiple data points is described for the interpretation of "radiostrontium" analyses. The method uses up to 10 or more counts on one sample, starting 1 d after the chemical separation. The unreliable "day-0" count on a relatively low activity sample is not used since it introduces too many uncertainties. The count data for each sample are compared against a spreadsheet-calculated matrix of ingrowth/decay curves from 0 to 100% 90Sr and at the analytical count intervals between about 24 to 650 h after the chemical separation to determine the best fit of the data set. This fit occurs where the decay/ingrowth characteristics of the sample, as defined by the changing counts, most closely match those of the matrix for all of the data points. At this fit, the 89Sr and 90Sr percentages are defined, and the best estimate of the "time-0" counts is calculated using all of the counts. Secondary separations and analyses are not required. PMID- 3335444 TI - In-vivo counting of 241Am in human lungs and tracheobronchial lymph nodes. AB - A study was conducted of a human male who had inhaled a mixture of 241Am and Pu. To distinguish 241Am deposited in the subject's lungs from translocated activity deposited in the tracheobronchial lymph nodes (TBLN), two intrinsic Ge detectors were collimated with 0.3-cm Pb sheeting. A tissue-equivalent phantom containing either 22.9 kBq (620 nCi) of 241Am in the lungs or a 81.4 kBq (2200 nCi) 241Am point source in the TBLN was measured. Calibration curves observed from lateral differential scans on the phantom were compared to data obtained by the same detection system for a human male with a measured lung deposition of 89 Bq (2.4 nCi) of 241Am. Comparison of the human data to the calibration curves indicated the activity was restricted primarily to the lungs. The calibration curves demonstrate that this method is useful in determining the distribution of inhaled radioactivity between the lungs and TBLN. The measured activity from the male subject generally supported the ICRP Publication 30 model translocation prediction for class Y compounds. PMID- 3335445 TI - Transfer from soil to plants of 106Ru as nitrosyl and as chloride. AB - The transfer of 106Ru in a soil-plant ecosystem was investigated with respect to two chemical forms in compact soil samples under greenhouse conditions with surface and deep-layer contamination. Considerable differences in the uptake of 106Ru were observed between 106RuCl3 and 106Ru-nitrosyl during the first 5-8 wk after the contamination of the soil. The translocation of 106Ru in the soil showed an inhomogeneous distribution of the radioruthenium, with a great part of the total activity remaining in the upper soil layer between 0 and 5 cm even 10 mo after contamination of the soil surface. During the whole experiment, reemission of 106Ru into the air was investigated by using special air collectors under different temperature and light conditions. Although a continuous checking out for a time of about 8 mo, no measurable concentrations of 106Ru could be out for a time of about 8 mo, no measurable concentrations of 106Ru could be found in examined air filters. PMID- 3335446 TI - Radiation induced heart disease in hypertensive rats. AB - Spontaneously hypertensive Wistar rats were given single doses of X rays to their heart. Irradiation decreased the blood pressure before any myocardial radiation damage was apparent. Male rats, which were more hypertensive than female rats, had a shorter survival time after local heart irradiation than female rats. Antihypertensive treatment with hydralazine did not increase the survival time. It is considered that myocardial hypertrophy is the cause of the increased susceptibility of spontaneously hypertensive rats to local heart irradiation. PMID- 3335447 TI - Malignant tumors of the nasal cavity and ethmoid and sphenoid sinuses. AB - Between October 1964 and December 1983, 48 patients with malignant tumors of the nasal cavity (31), ethmoid sinus (13), or sphenoid sinus (4) were treated with curative intent by radiation therapy. There were 21 squamous cell carcinomas, 14 minor salivary gland tumors (adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma), 3 malignant melanomas, 2 soft tissue sarcomas, and 8 esthesioneuroblastomas. Forty-two patients were treated with irradiation alone and six with planned combined irradiation and surgery. The 10-year actuarial local control rate for Stage I (limited to site of origin; 7 patients) was 100%; for Stage II (extension to adjacent sites, e.g., adjacent sinuses, orbit, pterygomaxillary fossa, nasopharynx; 19 patients) was 53%; and for Stage III (destruction of skull base or pterygoid plates, or intracranial extension; 22 patients) was 30%. Of 24 failures at the primary site, 10 occurred greater than 24 months after completion of irradiation. With the exception of adenoid cystic carcinoma (17% local control at 15 years), the ultimate local control rates for all histologies were in the range of 40% to 60%. Of 7 patients with documented intracranial extension, 3 (43%) remained free from local recurrence 3.5, 4, and 9 years after treatment. The 5-, 10-, 15-, and 20-year uncorrected actuarial survival rates for all 48 patients were 52%, 30%, 22%, and 22%, respectively. Continuous disease-free survival according to stage at 10 years was 86% for Stage I, 42% for Stage II, and 22% for Stage III. The single failure in a patient with Stage I disease was a lymph node metastasis that was successfully managed by radical neck dissection. The orbit was grossly invaded by tumor prior to treatment in 22 patients (46%). Sixteen (33%) of 48 patients developed unilateral blindness secondary to radiation retinopathy or optic neuropathy; in the majority of these patients the complication was anticipated because the ipsilateral eye was irradiated to a high dose. Four patients (8%) unexpectedly developed bilateral blindness 17, 35, 46, and 90 months following treatment owing to optic nerve injury. A discussion of possible means of avoiding this latter, unacceptable complication is included. PMID- 3335449 TI - Some implications of the Linear Quadratic model for tumor control probability. AB - To define an optimal radiation therapy strategy, the dependence of the probability of cure and of significant complications, on the parameters controlled by the radiotherapist must be determined. The recent success of the Linear Quadratic (LQ) model in constructing isoeffect relations for normal tissue damage and in describing in vitro cell survival curves, indicate that this model could be used to determine this dependence. The problem of tumor control is addressed. Using LQ model parameters obtained from human tumor cell lines, the sigmoid dose-response curves for controlling tumors of fixed size but of several histologies, with a fractionated course of radiotherapy is obtained. Except for squamous cell carcinoma, the calculated average tumor control doses (TCD37 or TCD50) are unrealistically low, but the model can be made more realistic by including inhomogeneities in the spatial dose distribution and heterogeneous tumor cell populations. The slope of the dose response curves are determined and the significance of the "relative slope" parameter rho as a measure of the number of cells in a tumor's most radioresistant clone is noted. The relation of the model's predictions to qualitative features of the experimental animal data for both tumor control and for normal tissue damage is discussed. Experiments to test the validity of this type of model are suggested. PMID- 3335448 TI - The distribution of power and heat produced by interstitial microwave antenna arrays: I. Comparative phantom and canine studies. AB - To adequately plan and administer localized hyperthermia with interstitial microwave antennas, the thermal distribution patterns generated by such antennas must be characterized. This study evaluated the performance of single node 915 MHz antennas operating either alone or as a 2 cm square array of four parallel antennas using both muscle-equivalent phantoms and canine thigh muscle. Two types of measurements were compared. Specific absorption rate (SAR), where temperature increases resulting from short duration microwave pulses were used to define power distribution, and temperature gradients during simulated hyperthermia treatments. SAR measurements in phantoms were comparable to those obtained in non perfused canine muscle demonstrating the usefulness of the phantom for these measurements. For a single antenna there was a rapid decrease in power radially which resulted in a steep thermal gradient at distances within 0.5 cm. However, the power generated by a four-antenna array was highest along its central axis and declined to approximately 50% near the antennas at the array periphery. Along the central axis of the array power decreased most rapidly distal to the antenna nodes. The distribution of temperature measured during simulated hyperthermia treatments in phantoms paralleled the SAR distribution and was comparable to the temperature gradient observed in perfused canine muscle, suggesting that phantoms could be used to predict temperature distributions in resting muscle tissue. PMID- 3335450 TI - Interstitial radiation therapy in the treatment of childhood soft-tissue sarcomas. AB - Between 1971 and 1985, 12 children and adolescents aged 0.7 to 19 years (median 4.7 years) with localized residual soft-tissue sarcomas (STS) underwent interstitial radiation therapy (IRT) at our institution. Eight received IRT as a component of initial therapy, and four were treated for recurrent or persistent disease. Tumor sites were head and neck (6), pelvis (4), extremity (1), and retroperitoneum (1). The radionuclides employed were Iridium-192 (9), Iodine-125 (2), and Californium-252 (1). The median prescribed dose in the Iridium-192 group was 3960 cGy (1955-7300). Seven of eight children receiving IRT during initial therapy have maintained local control, and six remain without evidence of disease for a median follow-up time of 5.8 years (2.0-16.0). One of the four patients treated for recurrent disease is free of disease after salvage surgery, and the other three are dead of disease. Multidisciplinary evaluation of the nine patients with more than 2 years of follow-up revealed functional and cosmetic effects of IRT to be minimal. IRT can be an effective method of delivering high dose irradiation in childhood sarcomas while reducing the deleterious effects in adjacent normal tissues. PMID- 3335451 TI - The development of Graves' disease following radiation therapy in Hodgkin's disease. AB - Radiation-related thyroid dysfunction is a common occurrence in patients with Hodgkin's disease treated with mantle field radiation. Although chemical and clinical hypothyroidism are most commonly seen, Graves' disease has also been described. We have examined the records of 437 surgically staged patients who received mantle field irradiation between April 1969 and December 1980 to ascertain the frequency of manifestations of Graves' disease. Within this group, seven patients developed hyperthyroidism accompanied by ophthalmic findings typical of those seen in Graves' disease. The actuarial risk of developing Graves' disease at 10 years following mantle irradiation for Hodgkin's disease was 3.3% in female patients and 1% in male patients in this study. The observed/expected ratios were 5.9 and 5.1 for female and male patients, respectively. This observed risk significantly exceeded that seen in the general population. PMID- 3335452 TI - The influence of lung density corrections on treatment planning for primary breast cancer. AB - Primary breast cancer is generally treated with opposed radiation beams oriented tangentially with respect to the breast. This technique attempts to minimize the dose to the lung and other normal tissues, while at the same time producing a uniform dose distribution throughout the irradiated breast. Although a part of the lung is always included in the tangential breast fields, the effect of this low density tissue on the dose distribution is rarely taken into account. In the present work, the effect of lung density correction on the dose distribution resulting from tangential breast fields is analyzed. Treatment plans for a series of 34 patients treated for breast cancer have been performed using CT data. To study the effect of density corrections on the tangential field treatment plans for these patients, eight separate treatment plans for each patient have been optimized. For each of four photon energies (60Co, and 4, 6, and 10 MV X rays), treatment plans have been optimized for each patient when density correction is employed, and when unit density is assumed. Four additional dose calculations have been obtained for each patient corresponding to use of the unit density plan, but with density corrections employed in the calculation. The effects that density correction has on the wedge angles used, on the maximum dose ("hot spot") for each of several cross-sectional cuts, on the prescription isodose level which is chosen for each plan, and on homogeneity of the dose distribution over the target volume are all analyzed for the above described plans. PMID- 3335453 TI - Remote afterloading techniques for the treatment of nasopharyngeal and endometrial cancer. AB - Simple methods of delivering intracavitary radiation to the nasopharynx and endometrium using remote afterloading apparatus are described. Considerable flexibility of isodose distribution is possible at both sites even without refinement of the systems described. PMID- 3335454 TI - Seduced by oxygen. PMID- 3335455 TI - The enigma of accelerated hyperfractionated radiation therapy for head and neck cancer. PMID- 3335456 TI - Is surfactant release a reliable predictor of radiation pneumonitis? PMID- 3335457 TI - Accelerated and hyperfractionated radiotherapy in advanced head and neck tumors: rebuttal. PMID- 3335458 TI - Analysis of late complications after rapid hyperfractionated radiotherapy in advanced head and neck cancers. AB - Late effects were analyzed in a series of 39 patients with a 2-year minimal follow-up who were treated by rapid hyperfractionated radiotherapy. The total dose was 66-72 Gy delivered in two series of 33-36 Gy separated by a 2-4 week rest interval. The number of daily fractions ranged from 8 to 6 and the interval between each fraction was 2 hr. Late complications consisted of cervical fibrosis, mucosal necrosis, bone necrosis, trismus, and laryngeal edema. Seventy percent of patients experienced late complications, and in 54% of cases, these reactions were considered severe, causing death in 13% of patients. No relationship was found between field sizes, dosimetric data and type and frequency of late effects. It is therefore suggested that the interval between two daily sessions in any multifractionated protocol may be of critical importance. PMID- 3335459 TI - The effect of young age on tumor recurrence in the treated breast after conservative surgery and radiotherapy. AB - Prognostic factors for local recurrence following conservative surgery and radiation therapy for patients with early breast cancer have not been fully established. To evaluate the importance of young age as a prognostic factor for local recurrence, we reviewed the results of treatment of 597 patients with 607 UICC-AJCC Stage I or II breast cancers, 47 of which were diagnosed when the patient was less than 35 years old. All were treated with excisional biopsy and a total dose to the site of the primary tumor of 60 Gy or more. The median follow up in survivors was 63 months. Patient age and the presence of an extensive intraductal component (EIC) were both highly associated with the likelihood of tumor recurrence in the treated breast. Patients under 35 had an actuarial 5-year recurrence rate of 26%, compared to 10% for older patients (p = 0.002). Patients with an EIC had a breast recurrence rate of 25%, compared to 5% when EIC was absent (p less than 0.0001). Although the incidence of an EIC was higher in the younger subgroup (44% vs. 31%), this alone did not account for the difference in in breast recurrence rates, since younger patients had a higher recurrence rate than older patients even when an EIC was absent (22% vs. 3%, p = 0.0003). We conclude that the age of the patient is an important prognostic factor for local recurrence following conservative surgery and radiation therapy. This finding is in part attributed to the observation that younger women are more likely to have tumors with an EIC than older women, but even when an EIC is absent, they may be at an increased risk of local recurrence. However, caution is required in interpreting these findings with regard to selecting among treatment options until further data are available comparing the results of conservative surgery and radiation therapy to those of mastectomy in younger patients. PMID- 3335460 TI - Preoperative radiation and chemotherapy for localized squamous cell carcinoma of the esophagus: a RTOG Study. AB - Forty-one evaluable patients with localized squamous cell carcinoma of the thoracic esophagus were treated by a course of radiation therapy (3000 cGy in 3 weeks), 5-Fluorouracil (5-FU) and Cis-platinum (Pt). This was followed by an esophagectomy in medically eligible patients who agreed to the procedure and who had no evidence of extrathoracic tumor. If tumor was found in the specimen, an added 2000 cGy of radiation therapy and additional 5-FU and Pt were given. One year survival was 44%, 2-year survival 15%, and 3-year survival 8%. All 3-year survivors had tumor-free specimens, but one patient with tumor in the thorax and subdiaphragmatic metastasis survived 2 years. PMID- 3335461 TI - Combined chemoradiotherapy in limited-disease, inoperable non-small cell lung cancer. AB - Forty-three patients with limited-disease, inoperable non-small cell lung cancer received two intravenous courses of cyclophosphamide, Adriamycin, and cisplatin (CAP) chemotherapy over a 6-week period. This was followed by 5 weeks of combined chemoradiotherapy (CCRT) consisting of low weekly doses of CAP for 5 weeks plus 50 Gy continuous X ray therapy (XRT) to the primary tumor site. Chemotherapy was continued until disease progression occurred or until the total dose of Adriamycin reached 450 mg/m2, whichever came first. CCRT improved the response rate [complete response (CR) plus partial responses (PR)] from 25% after two courses of CAP alone to 65% after CCRT. Previous response to two courses of CAP influences response subsequent to CAP plus XRT. A pretherapy weight loss of 6% or greater had a significant adverse effect on both response and survival time. The median survival time for all patients was 50 weeks; patients whose disease responded to treatment survived significantly longer than patients with nonresponding disease. The median time until disease progression was 37 weeks. Twenty-seven patients relapsed. The first sites of relapse were local in 30% of the patients, distant in 56% of them, and both local and distant in 15%. Severe esophagitis occurred in 30% of the patients and was dose-limiting. The administration of CCRT resulted in an improved response rate compared with the rates reported in previous studies of chemotherapy or radiotherapy alone. Further improvement of the CCRT program is needed to increase long-term survival time and to decrease esophageal toxicity. PMID- 3335463 TI - The role of computed tomography in the evaluation of post-mastectomy locally recurrent breast cancer. AB - The rate of post mastectomy local-regional recurrence of breast cancer has remained in the range of 10-30% for decades. The traditional treatment, external beam radiation therapy, is successful in eradicating local disease in most cases, but re-recurrences are seen in about 50% of patients. Since 1982, 33 patients with such recurrences have undergone evaluation with computed tomography (CT) at our institution as part of their diagnostic work-up. In 22/33 (67%), CT revealed unsuspected disease, and in 10 of these patients the radiation treatment plan had to be altered. These results, similar to three other published series, strongly suggest that CT is a necessary part of the work-up of patients with post mastectomy local-regional recurrences. The significance of these findings with respect to the cause of post mastectomy local-regional failures is further discussed. PMID- 3335462 TI - Absence of prognostic significance, peritoneal dissemination and treatment advantage in endometrial cancer patients with positive peritoneal cytology. AB - Peritoneal cytology has been shown to be one of the prognostic factors in endometrial cancer. A series of 134 patients was seen between January 1977 and March 1985 with clinical Stage I (or treated as a clinical Stage I) endometrial adenocarcinoma at the University of Rochester Cancer Center. The majority of patients underwent extrafascial hysterectomy with the majority of washings obtained at the time of surgery. Fourteen percent (19/134) of the patients were found to have positive cytology. Eleven patients with positive cytology (11/19) were treated with local-regional pelvic treatment; the other eight patients received whole abdominal therapy. The recurrence rates were less with the local treatment than with the whole abdominal treatment groups (9.1% vs. 25%) in those patients having positive cytology. There was no statistical difference in recurrence rates between the pathologic Stage I patients with positive cytology (10%) versus those patients having negative cytology (5%), nor was there statistical difference in survival between pathologic Stage I positive or negative cytology patients. It is suggestive from this non-randomized study that positive cytology in endometrial cancer is not an independent prognostic factor and that whole abdominal irradiation did not influence outcome. PMID- 3335464 TI - Radiation dose response of normal brain. AB - Dose response relationships were determined after hemibrain x-irradiation of normal beagle dogs. Radiation doses of 11.5, 13.5, 14.3, and 17 Gy were delivered in a single dose and results were compared to previous studies using doses of 15 and 30 Gy. Brain injury was quantified using computed tomography (CT), with serial studies obtained monthly up to 1 year following irradiation. Quantitative endpoints included low density volume and contrast enhancement. Doses above 14.3 Gy resulted in high lethality 5-8 months following irradiation, and an LD50 of 14.9 Gy was calculated. At these lethal doses, low density volume representing edema, demyelination, and necrosis had a similar response with an ED50 of 14.6 Gy. Radiation-induced decreases in white matter density appeared 5-6 months after sublethal doses (less than or equal to 14.3 Gy) and the volume of tissue characterized by this low density increased with time and dose. This sublethal low density change had an ED50 of 12.8 Gy, and may reflect a loss or generalized atrophy of glial cells and/or myelin. These results show that: (a) the dose response curves obtained after hemibrain x-irradiation are extremely steep; and (b) at least two processes may be involved in the development of late radiation damage, one that is rapid upon onset (a "delayed acute" reaction) and the other which is a slower and more degenerative process. PMID- 3335465 TI - The efficacy of combined chemotherapy and radiotherapy in advanced non-metastatic breast cancer. AB - Thirty-five patients with locally advanced (inoperable) breast cancer have been treated based on a regimen of chemotherapy-radiotherapy-chemotherapy. At the completion of all treatment a complete remission rate of 86% was achieved with acceptable toxicity. At a median follow-up of 24 months (range 4-60), relapse at the site of bulk disease occurred in 17% (10% isolated loco-regional relapse) and relapse at distant sites in 34%. The median relapse-free survival was 36 months and the median survival has not yet been reached. Following initial promising results in terms of loco-regional disease control in this group of high-risk patients, the protocol was extended to include 34 patients defined as having locally extensive disease. All patients in this subgroup had undergone a modified radical mastectomy and were categorized as (a) patients in whom the pre-operative clinical findings merited (in our opinion) inclusion in the category of locally advanced (inoperable) disease, (b) patients in whom the primary was operable but in whom extensive involvement of axillary nodes was found (greater than 10 nodes positive or greater than or equal to 70% nodes positive if less than 10 nodes found) and (c) patients without the above characteristics with a primary tumor greater than 8 cm. At a median follow-up of 23 months (range 4-48), loco-regional recurrence occurred in one patient (3%) but distant relapse occurred in 21%. Relapse-free and overall survival was not significantly different to that found in patients with locally advanced disease who did not undergo mastectomy. PMID- 3335466 TI - Cardiac output and regional myocardial contraction in anorexia nervosa. AB - The study measured cardiac output and assessed regional myocardial contraction in 14 patients with anorexia nervosa, some of whom also had bulimia, and in 15 controls. The experimental and control groups were not significantly different in age or body surface area (p = greater than 0.05). To evaluate regional myocardial contraction, 12 of 14 anorexia nervosa-bulimia (ANB) patients were studied in the acute phase and once serially at a mean interval of 1.5 years by assessing the movement of each left ventricular wall segment toward the center of the ventricle as imaged in the precordial short axis. Cardiac output was measured in the ascending aorta by pulsed Doppler for control subjects and for 13 ANB patients. Regional myocardial contraction was normal for all controls, but eight of 14 ANB patients showed regional myocardial contraction abnormalities. Between studies, four of these eight demonstrated improved regional myocardial contraction, three remained unchanged, and one was worse. Mean cardiac output was markedly reduced in ANB patients (2.6 L/min) compared to controls (4.5 L/min) (p = less than 0.001). The low cardiac output in ANB patients was reflected as reduced mean ascending aortic velocity/second (18.5 cm/s) compared to a mean of 22.8 cm/s for controls (p = less than 0.02). Mean ascending aortic area was slightly smaller for ANP patients. Mean peak ascending aortic velocity was significantly lower in ANB patients than in controls (p = less than 0.02). Mitral valve prolapse was seen during at least one examination in seven of 14 ANB patients (0/15 controls) and disappeared in two of three patients following hydration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335467 TI - Delayed sleep phase syndrome in adolescents. AB - The delayed sleep phase syndrome is characterized by difficulty in falling asleep at a socially acceptable time of night and an inability to be easily aroused in the morning. Most commonly encountered in adolescents, this condition can produce daytime sleepiness and poor school performance, and it can lead to behavioral problems. The clinical features of the syndrome are described in 22 adolescents. Nine subjects participated in a protocol of polysomnographic recordings to simulate habitual "weekday" and "weekend" sleep patterns. There was a significant increase in total sleep time (p less than 0.005) and REM sleep (p less than 0.001) during the "weekend" sleep period. A multiple sleep latency test was performed between the two nights to assess daytime sleep tendency. Daytime sleepiness was maximal in the morning, with a tendency for greater alertness as the day progressed. The reduced amount of REM sleep during the "weekdays" plus the tendency for sleepiness in the mornings may contribute to the behavioral and educational difficulties seen in these patients. Recognition of this syndrome enables a specific sleep schedule change to be made that effectively treats the problem. PMID- 3335468 TI - Treatment and follow-up of obesity in adolescent girls. AB - An intervention program was conducted for 12 postmenarche, 12-15-year-old obese girls. Weight Winners, a multicomponent and multidisciplinary after-school intervention program, was developed in which behavior modification, aerobic exercise, and modeling appropriate behaviors for weight control were emphasized. Evaluation made before and immediately after the intervention and at a nine-month follow-up suggested that the after-school treatment program was successful in: 1) reducing the rate of gain and decreasing body weight by 11% while maintaining lean tissue and resting energy expenditure (REE), and 2) improving eating and exercise behaviors. Significant changes in eating behaviors (p less than 0.05) were: more low-calorie, nutritionally dense foods were consumed; the frequency and amount eaten decreased; and the speed of eating slowed. Implementing a fee contingent on attendance and on record keeping appeared to reduce attrition. Subjects cited the Weight Winners program, aerobic exercise, changes in eating behaviors, group and family support, and encouragement and praise from the group leaders as important contributions to their success in weight control. Barriers to change were reported by participants as boredom, hunger, lack of family and peer support, and having food in sight. An increase in lean tissue was associated with both improved self-esteem (p less than 0.05) and improved self-control (p less than 0.05). Subjects who had been obese the longest were the most responsive to hunger cues (p less than 0.05). PMID- 3335470 TI - Physicians' values and experience during adolescence. Their effect on adolescent health care. AB - The values and experience of physicians as adolescents can effect their care of adolescent patients. Eighty residents were studied using extensive personal data gathered from a structured interview, a questionnaire of perceived clinical skills, and a videotape with a simulated patient. A "values" and "risk-taking during adolescence" score was constructed and related to the resident's perceived skills for and attitudes about adolescent health care. Residents with higher values scores (more conservative) were more likely to be pediatric than internal medicine residents and less likely to prescribe birth control pills to an adolescent. Residents with higher risk-taking scores considered themselves more skilled in dealing with substance abuse and sexually transmitted diseases and in recognizing psychologic problems. Values or risk-taking scores were not related to the resident's perceived skill in areas such as evaluating hypertension or performing Tanner staging. These data suggest that certain values and experiences may be influential in the physician's ability and approach to dealing with certain issues related to adolescent health care. PMID- 3335471 TI - Obtaining a sexual history from adolescent girls. A preliminary report of the influence of age and ethnicity. AB - This preliminary study was undertaken to explore the hypothesis that socioeconomic and racial, as well as medical, factors influence the physician's decision about obtaining a sexual history from an adolescent female. Sixty consecutive medical records of adolescent-age emergency room patients with acute abdominal pain were classified according to ethnic group and socioeconomic status and searched for evidence that a sexual history had been taken. The study revealed a much higher number of recorded sexual histories among blacks and Hispanics. Although the absence of such a history seemed to have little relationship to diagnostic accuracy, a sensitive selectivity in exposing acutely ill teenagers to possible embarrassing questions appeared to be reserved for white, middle-class teenagers. PMID- 3335469 TI - Substance use and health activities of pregnant adolescents. AB - Little is known about substance use by pregnant adolescents or the possible effects of such use on their offspring. In this case-control study, substance use and selected health and social variables of 119 pregnant and 313 nonpregnant inner-city high school students are assessed. The most commonly used substances are alcohol, cigarettes, and marijuana. Pregnant subjects used substances similarly to their nonpregnant counterparts, but were more likely to smoke cigarettes. Pregnant and nonpregnant subjects thought a baby is put at great risk for harm if its mother uses a substance during pregnancy. Pregnant subjects demonstrated more positive health behaviors than nonpregnant subjects. Recommendations for intervention are discussed. PMID- 3335472 TI - Assessment of self-care agency in chronically ill adolescents. AB - This study evaluates the reliability and validity of the Denyes' instrument to measure self-care agency in adolescents and identifies significant correlates of agency in a sample of chronically ill adolescents. This descriptive cross sectional study used a convenience sample of 51 adolescents having asthma, diabetes, and convulsive disorders. Internal consistency estimates of questionnaire factors ranged from alpha 0.65 to 0.87 except in one instance (attitude toward health, 0.17). Construct and concurrent validity were supported as self-care agency factors were significantly related to health practices and status. Of multiple demographic variables, only gender demonstrated significant correlations with any self-care factors, whereas gender and disease type displayed a significant interaction effect across three factors. Although assessment of factor stability remains, the Denyes' instrument appears to be a potentially useful research and clinical assessment tool to measure self-care agency in adolescents with a severe chronic illness. PMID- 3335473 TI - The development of independence in adolescents with cystic fibrosis. AB - This study assessed the development of independence and its interaction with some biologic factors. Sixty-four adolescents with cystic fibrosis (CF) were compared with 36 adolescents with bronchial asthma, 47 healthy but small adolescents, and 71 normal healthy controls. A structured interview was designed to measure eight elements of independence. Adolescents with CF showed less responsibility for their own body hygiene and a delay in intimacy and sexuality, both correlated with puberty not yet having started. They also took less part in a number of social activities outside the home. There were minimal or no differences between ill and healthy adolescents for four elements. The results indicated that in future research, different types of independence should be taken into account. The correspondences between the chronically ill and the healthy adolescents prevailed over the differences. The main differences could be interpreted in terms of realistic coping with the illness and maintaining hope for the future. PMID- 3335474 TI - Sexually transmitted diseases and sexual behavior in urban adolescent females attending a family planning clinic. AB - Specimens from the lower genital tract of 102 sexually active urban adolescent females were tested for the common sexually transmitted diseases (STDs). The results were correlated with concomitant clinical, demographic, and historic data. Forty-one percent (42/102) were infected with one or more of the following organisms: Chlamydia trachomatis (26/102), Trichomonas vaginalis (13/102), Neisseria gonorrhoeae (10/102), yeast (6/102), condyloma (5/102), and herpes simplex virus (1/44). Mixed infections were found in 13%. Fifty-nine percent were negative for any infectious agents. The presence of genitourinary symptoms were of no value in predicting an STD. The rate of positive physical findings was significantly higher in the STD-positive group than in the negative group (p = 0.03), but 28% of the STD-negative group had positive physical findings, and 50% of the STD-positive group had normal physical findings. A history of genitourinary complaints or presence of physical findings was not predictive of a positive STD culture. Oral contraceptive use of more than six months appears to be a risk factor for an STD. No other factors, including the number of sexual partners, were significantly correlated with the presence of an STD. This study supports the need for routine screening of sexually active urban adolescent girls for an STD. PMID- 3335475 TI - Asymptomatic Chlamydia trachomatis infections in teenage males. AB - This study examined the prevalence of Chlamydia trachomatis infections of the urethra in asymptomatic teenage males in a juvenile detention setting. Gonorrhea cultures, chlamydia smears using the direct immunofluorescent antibody (DFA) technique, and 15-20 ml of a first-catch urine (FCU) sample were obtained. Of the 227 adolescent males screened, 205 had experienced sexual intercourse. Twenty seven (13.2%) of the sexually active adolescents had positive DFA smears for C. trachomatis. Three (1.5%) had positive Neisseria gonorrhoeae cultures. A urine leukocyte count of greater than 10 per high-power field gave a 91% specificity but only a 26% sensitivity for a positive DFA. The high prevalence of chlamydia in this population and the relative low cost of the DFA screen for chlamydia make this a useful procedure for discovering unsuspected disease, particularly in a high-risk population. The FCU screen for leukocytes was of limited value in identifying asymptomatic infection. PMID- 3335476 TI - An evaluation of urethral smear by Papanicolaou stain in men with urethritis. AB - The objective of this study was to evaluate the usefulness of a Papanicolaou stained urethral smear (Pap smear) to identify sexually transmitted disease (STD) pathogens in men with urethritis. Specimens from the endourethra were obtained for Chlamydia trachomatis and Neisseria gonorrhoeae cultures, a Gram stain, and a Pap smear in 24 symptomatic men aged 16-22 years. All Pap smears were read independent of the culture results. Based on the laboratory techniques employed, nine subjects had gonococcal urethritis (GU), and 11 had nongonococcal urethritis (NGU). Four subjects with GU had concomitant infection with another STD pathogen(s). Papanicolaou smear alone identified four different pathogens in 16 subjects, chlamydia in ten, trichomonads in two, intracellular diplococci in two, multinucleate giant cells of herpes in one, and chlamydia and trichomonad together in one. Out of 11 chlamydia-positive Pap smears, three had a positive culture. One subject had a positive chlamydia culture and a negative Pap smear. Two subjects with intracellular diplococci on Pap smear had culture-confirmed gonorrhea. The Pap smear was useful in identifying some of the different pathogens in NGU, especially trichomonads and herpes, not recoverable by commonly used techniques and in the diagnosis of concomitant infection by more than one STD pathogen in GU. Adding the Pap smear to the diagnostic tests for urethritis increased the etiologic diagnoses from 37.5% to 79%. PMID- 3335477 TI - Gross hematuria as a manifestation of infectious mononucleosis. AB - Gross hematuria is an uncommon manifestation of infectious mononucleosis. This report describes a 19-year-old male with infectious mononucleosis who developed gross hematuria. Infectious mononucleosis should be considered in the differential diagnosis of adolescents with hematuria. PMID- 3335478 TI - The fear of AIDS. Guidelines to the counseling and HTLV-III antibody screening of adolescents. PMID- 3335479 TI - Contraceptive use in the chronically ill adolescent female. PMID- 3335480 TI - Changes in the hydrophobic-hydrophilic cell surface character of Halomonas elongata in response to NaCl. AB - Phase-partitioning studies of the euryhaline bacterium Halomonas elongata demonstrated that the hydrophobic-hydrophilic nature of the cell surface changed as the bacterium grew in different NaCl concentrations. Mid-log-phase cells grown in a high (3.4 M) NaCl concentration were more hydrophilic than were cells grown in a low (0.05 M) NaCl concentration. Mid-log-phase cells from defined medium containing 3.4 M NaCl normally produced a hydrophobicity reading of only 14 (hexadecane hydrophobicity = 100), while corresponding cells from defined medium containing 0.05M NaCl gave a hydrophobicity reading of 90. Compared with cells grown in low salt concentrations, cells grown in high salt concentrations were more hydrophilic at all stages of growth. Rapid suspension of log-phase cells grown in 1.37 M NaCl into a 0.05 or 3.4 M NaCl solution produced no detectable rapid changes in surface hydrophobicity. These data suggest that as H. elongata adapts to different NaCl concentrations, it alters the affinity of its outermost cell surface to water. PMID- 3335481 TI - Gene organization and structure of the Streptomyces lividans gal operon. AB - We present the gene organization and DNA sequence of the Streptomyces lividans galactose utilization genes. Complementation of Escherichia coli galE, galT, or galK mutants and DNA sequence analysis were used to demonstrate that the galactose utilization genes are organized within an operon with the gene order galT, galE, and galK. Comparison of the inferred protein sequences for the S. lividans gal gene products to the corresponding E. coli and Saccharomyces carlbergensis sequences identified regions of structural homology within each of the galactose utilization enzymes. Finally, we discuss a potential relationship between the gene organization of the operon and the functional roles of the gal enzymes in cellular metabolism. PMID- 3335482 TI - Energy-dependent transport of nickel by Clostridium pasteurianum. AB - The mechanism of nickel transport by Clostridium pasteurianum was investigated by using 63NiCl2 and a microfiltration transport assay. Nickel transport was energy dependent, requiring either glucose or sucrose; xylose and o-methyl glucose did not support growth, butyrogenesis, or transport. Transport was optimum at pH 7 and 37 degrees C, and early-stationary-phase cells had the highest propensity for nickel transport. The apparent Km and Vmax for nickel transport approximated 85 microM Ni and 1,400 pmol of Ni transported per min per mg (dry weight) of cells, respectively. On the basis of metal specificity, nickel appears to be transported primarily by a magnesium transporter, although an alternative nickel transporter may also be involved. ATPase inhibitors (N,N'-dicyclohexylcarbodiimide, tributyltin chloride, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole, and quercetin), protonophores (carbonyl cyanide m-chlorophenylhydrazone, 2,4-dinitrophenol, and gramicidin D), metal ionophores (valinomycin, monensin, and nigericin), benzyl viologen, carbon monoxide, and oxygen inhibited nickel transport. Nickel transport was coupled indirectly to butyrogenesis and was dependent on the energy state of the cell. PMID- 3335483 TI - Nucleotide sequence of the type A staphylococcal enterotoxin gene. AB - We determined the nucleotide sequence of the gene encoding staphylococcal enterotoxin A (entA). The gene, composed of 771 base pairs, encodes an enterotoxin A precursor of 257 amino acid residues. A 24-residue N-terminal hydrophobic leader sequence is apparently processed, yielding the mature form of staphylococcal enterotoxin A (Mr, 27,100). Mature enterotoxin A has 82, 72, 74, and 34 amino acid residues in common with staphylococcal enterotoxins B and C1, type A streptococcal exotoxin, and toxic shock syndrome toxin 1, respectively. This level of homology was determined to be significant based on the results of computer analysis and biological considerations. DNA sequence homology between the entA gene and genes encoding other types of staphylococcal enterotoxins was examined by DNA-DNA hybridization analysis with probes derived from the entA gene. A 624-base-pair DNA probe that represented an internal fragment of the entA gene hybridized well to DNA isolated from EntE+ strains and some EntA+ strains. In contrast, a 17-base oligonucleotide probe that encoded a peptide conserved among staphylococcal enterotoxins A, B, and C1 hybridized well to DNA isolated from EntA+, EntB+, EntC1+, and EntD+ strains. These hybridization results indicate that considerable sequence divergence has occurred within this family of exotoxins. PMID- 3335485 TI - Alprazolam in the treatment of social phobia. AB - Pharmacological treatment of social phobia has not been extensively studied. Recent reports suggest that social phobia may be treated with monoamine oxidase inhibitors, tricyclic antidepressants, beta-blockers, or clonidine. The authors describe four patients with social phobia who responded moderately to markedly well when treated with the triazolobenzodiazepine alprazolam. Patients with social phobia and patients with agoraphobia with panic attacks differ in the focus of anxiety, sensitivity to lactate infusion, and the pattern of symptoms during anxiety episodes. However, there is significant overlap in the clinical features of these two patient groups. The preliminary finding that several types of pharmacological agents that are effective in treating agoraphobia with panic attacks may also be effective in treating social phobia suggests that the two disorders may share some common pathophysiology. PMID- 3335486 TI - Reversible depression in Binswanger's disease. AB - The authors describe four elderly patients with Binswanger's disease in whom depression was prominent. Therapy with antidepressant drugs in three patients produced major improvement in psychological and physical functions. The one patient who could not be given an adequate course of antidepressant therapy because of intercurrent illness improved spontaneously after many months. The authors conclude that depression associated with Binswanger's disease is reversible despite persistence of neurological abnormalities. They speculate that this depressive syndrome is an example of organic affective disorder due to diffuse subcortical white matter ischemic lesions of the cerebral hemispheres and discuss the possible neuroanatomical basis of the depression. PMID- 3335487 TI - Mood-related obsessive-compulsive symptoms in a patient with bipolar affective disorder. AB - The authors present a case of coexisting obsessive-compulsive disorder (OCD) and bipolar affective disorder in which the obsessive-compulsive symptoms disappeared during episodes of mania and reappeared during periods of depression. Although patients with coexisting bipolar disorder and OCD are relatively rare, careful study of those patients may increase our understanding of the complex relationship between obsessive-compulsive symptoms and mood. Abnormalities in serotonergic neurotransmission have been postulated in both affective disorders and OCD and may provide important clues to the pathophysiology of OCD. PMID- 3335484 TI - Mode of action of the staphylococcinlike peptide Pep 5: voltage-dependent depolarization of bacterial and artificial membranes. AB - The cationic staphylococcinlike peptide Pep 5 is shown to depolarize bacterial and planar lipid membranes in a voltage-dependent manner. An artificial valinomycin-induced potassium diffusion potential across the cytoplasmic membrane of Staphylococcus cohnii 22 was sufficient to promote Pep 5 action. Thus, evidence is provided that a membrane potential of sufficient magnitude is the only prerequisite for Pep 5 activity. The voltage dependence was elucidated by macroscopic conductance measurements with black lipid membranes. A threshold potential of about -90 to -100 mV, which was deduced from experiments with bacterial cells, could be confirmed. Single pores were resolved which often occur as short-lived bursts and fluctuate among different conductance levels. Pore diameters were calculated ranging from 0.1 to 1 nm. Succinylation of the lysine residues of Pep 5 resulted in prolonged pore lifetimes and maintenance of distinct conductance levels. However, the succinylated peptide required a higher threshold potential, approximately -150 mV, than the native peptide, which is probably the reason for the reduced activity of the modified peptide against intact gram-positive bacteria. PMID- 3335488 TI - Desipramine and testicular swelling in two patients. AB - Two patients are described who developed testicular swelling and pain during treatment with desipramine. The symptoms disappeared when desipramine was discontinued and in one case returned when desipramine treatment was reinitiated. The observations suggest that testicular swelling and pain are side effects of desipramine. PMID- 3335489 TI - Rhabdomyolysis and molindone. PMID- 3335490 TI - Carbamazepine treatment for stuttering. PMID- 3335491 TI - Mysterious MAOI hypertensive episodes. PMID- 3335492 TI - Phenomenology of panic attacks: a descriptive study of panic disorder patients' self-reports. AB - The phenomenology of panic disorder and panic attacks was systematically assessed in 46 consecutive patients. The results suggest that DSM-III criteria include several symptoms that are not frequently present during a panic attack and that DSM-III's characterization of a panic attack is imprecise and misleading. Panic attacks were found to vary in intensity, frequency, spontaneity, and associated symptoms. A panic attack typically presents as a unified symptom complex of psychic anxiety and multiple somatic symptoms in multiple body systems. It occurs in a crescendolike pattern, is self-limited, and often leaves the subject weak or shaken. The temporal course as much as the symptomatic presentation defines a panic attack. PMID- 3335493 TI - Calcium-independent, pH-regulated effects of S-100 proteins on assembly disassembly of brain microtubule protein in vitro. AB - At alkaline pH, Ca2+ is no longer required for S-100 proteins to inhibit the assembly and to promote the disassembly of brain microtubules in vitro, though the presence of Ca2+ significantly favors the S-100 effects. These effects are inversely related to the microtubule protein concentration and directly related to the S-100 concentration and the pH. Ca2+-independent, pH-regulated inhibition of assembly of phosphocellulose-purified tubulin by S-100 is also described. The microtubule disassembling effect of S-100 is additive to that of alkali (used to raise the pH), and S-100 further disassembles microtubules after alkalinization. Thus the larger inhibitory effect of S-100 on microtubule assembly at alkaline versus acid pH depends on both a decrease in the assembly rate and an increase in the disassembly rate. Together with previous data on this topic, the present findings indicate that S-100 proteins act on microtubule protein in vitro primarily by binding to tubulin, this event being Ca2+-regulated at a given pH, and pH-regulated at a given free Ca2+ concentration. PMID- 3335494 TI - Purification and characterization of two glycopeptide hydrolases from jack beans. AB - Two glycopeptide hydrolases, an endo-beta-N-acetylglucosaminidase and peptide:N glycanase (amidase), have been isolated from defatted jack bean meal by standard procedures involving differential solubility and column chromatography. The purified products appear to be free of contaminating proteases and exoglycosidases, and their substrate specificity has been explored with regard to both glycan and peptide structure of the substrates. The endoglycosidase appears to be specific for high mannose glycans; no hydrolysis of either hybrid or complex glycans has been observed. It shows limited activity with two intact glycoproteins, ribonuclease B and yeast invertase, and gives optimal rate with glycopeptides. Free glycan-Asn derivatives are poor substrates in comparison with glycopeptides or glycan-Asn derivatives where the alpha-amino group has been dansylated. The amidase will liberate both high mannose, hybrid, and asialo complex glycans from both proteins and peptides, but many glycans in intact proteins or in long peptides are resistant to the amidase and become active as substrates only after further proteolytic cleavage. The best substrates appear to be those with the glycosylated asparagine no more than 4-5 residues in from either the NH2- or COOH-terminal end of the peptide. Sialylated glycans do not appear to be released by the amidase. PMID- 3335496 TI - High affinity phlorizin binding to the LLC-PK1 cells exhibits a sodium:phlorizin stoichiometry of 2:1. AB - The phlorizin binding properties of luminal membrane vesicles isolated from the LLC-PK1 cells, a continuous epithelial cell line derived from pig kidney, are studied. Scatchard analysis of this binding indicates the existence of a single high affinity sodium-dependent site with KD = 0.4 microM at 266 mM sodium. The specificity properties of this site indicate that it represents the binding of phlorizin to the hexose binding site of the sodium-dependent D-glucose transporter previously identified in this cell line. Both phlorizin equilibrium binding and the rate of phlorizin binding were found to be sigmoidal functions of sodium concentration. A Hill analysis of these data was consistent with a sodium:phlorizin stoichiometry of 2:1 in good agreement with the sodium:glucose stoichiometry already established in these cells. Phlorizin dissociation was also found to be sodium-dependent. On the basis of the phlorizin binding data presented here, a number of models of the binding of phlorizin and sodium to the transporter can be excluded. An analysis of a random binding model consistent with the data is presented. The significance of the LLC-PK1 sodium-dependent D glucose transporter as a model system for related renal and intestinal transporters is discussed. PMID- 3335495 TI - Cyanide binding to Cu, Zn superoxide dismutase. An NMR study of the Cu(II), Co(II) derivative. AB - The Cu,Co superoxide dismutase derivative, in which the native Zn(II) was replaced by Co(II), was investigated by 1H NMR spectroscopy at pH 7.0 in the presence of CN- and N-3. Addition of either anion produced large but remarkably different variations in the position of the histidine proton signals bound to the metal cluster. The resonances of the histidines bound to the copper broadened at low CN- concentrations (6 X10(-5)-16.5 X 10(-3) M KCN, in the presence of 1.5 mM protein) and narrowed again, with changed chemical shifts at [KCN] greater than 10(-2) M. At 7 degrees C two resonances split into two pairs of lines as a function of [CN-]. The temperature dependence of these resonances, in the presence of nonsaturating [CN-], suggests a slow exchange between two forms of the protein-bound copper in the presence of the anion. The apparent activation parameters associated with the interconversion of the two species indicate a local conformational change in the presence of CN-. No evidence of temperature dependence was seen in the spectrum in the presence of N-3, which, on the other hand, was fully removed from the copper by addition of CN-. No evidence was obtained for removal by CN- of a histidine bound to the copper as previously reported for low affinity anions at pH 5.5 (Bertini, I., Lanini, G., Luchinat, C., Messori, L., Monanni, R., and Scozzafava, A. (1985) J. Am. Chem. Soc. 107, 4391-4396). These results indicate that CN- has a unique pattern of binding to the enzyme copper. Since catalytic and structural data indicate that CN- is the only appropriate substrate analogue for the Cu,Zn superoxide dismutase, data from anions with much less affinity may lead to misleading conclusions on the mechanism of anion and substrate binding to the enzyme. PMID- 3335497 TI - Location of specific oligosaccharides in heparin in terms of their distance from the protein linkage region in the native proteoglycan. AB - Studies were conducted to define the location of components and sequences in heparin with respect to their distance from the peptide linkage in the native proteoglycan. A purified heparin-oligopeptide was linked via its amino terminus to a matrix containing an azo bond and an activated carboxyl group. The polysaccharide chain was maximally degraded, either with heparinase or nitrous acid, and the soluble products were removed. The heparin-oligopeptide fragments that remained on the matrix were released by reductive cleavage of the azo linkage and characterized. The fragments, as well as heparin released without prior degradation, contained serine and glycine as the principal amino acids; the ratio of galactose to xylose was 2:1. The ratio of glucosamine to serine of 33:1 in the undegraded heparin was reduced to 6:1 and 1:1 in the heparinase-treated and nitrous acid-treated products, respectively. The undegraded sample and the fragments contained phosphate in equivalent amounts, demonstrating its presence in the heparin-protein linkage region. The heparin-oligopeptide preparation was also fractionated by gel filtration and high and low molecular weight fractions thus obtained were each linked to the insoluble matrix. The products that were subsequently released were subfractionated on a molecular weight-calibrated column of Sephadex G-200, and eluates were assayed for activity in promoting the neutralization of thrombin and factor Xa by antithrombin. The results revealed a sharp decrease in specific activity in heparin-oligopeptide fractions below Mr = 15,000 indicating that the anticoagulant-conferring segment is located at about 20 disaccharide units away from the peptide linkage region. PMID- 3335498 TI - A region in the steroid binding domain determines formation of the non-DNA binding, 9 S glucocorticoid receptor complex. AB - This work was initiated to determine if a specific region of the glucocorticoid receptor determines the formation of the inactive (i.e. non-DNA-binding) 9 S form of the receptor recovered in cytosol preparations. It is known that the murine glucocorticoid receptor of the nti phenotype, which consists of only the carboxyl terminal 40-kDa peptide containing the DNA-binding and steroid-binding domains separated by a short linker region, is recovered in hypotonic lysates as a 9 S heteromeric complex (Gehring, U., and Arndt, H. (1985) FEBS Lett. 179, 138-142). To further localize the domain required for formation of the 9 S complex, we have determined the sedimentation coefficients of receptors produced in COS-7 cells transfected with several mutants of the human glucocorticoid receptor gene. Deletion of the DNA-binding domain results in a 9 S complex that is somewhat less stable than the wild type receptor during sucrose gradient centrifugation. Deletion of the linker region yields a molybdate-stabilized 9 S complex, but deletion of the entire steroid-binding domain or internal deletion of the amino terminal two-thirds of this domain yields receptors that are constitutive transcriptional activators and are present in cytosol only in the 4 S form. Taken together, these observations demonstrate that the steroid-binding domain contains the features required for formation of the 9 S heteromeric complex, and they are consistent with the proposal that the steroid-binding domain normally represses receptor function. PMID- 3335500 TI - Amino acid sequence of the calcium-binding light chain of myosin from the lower eukaryote, Physarum polycephalum. AB - We have established a new method for preparing Physarum myosin whose actin activated ATPase activity is inhibited by micromolar levels of Ca2+. This Ca2+ inhibition is mediated by the Ca2+ binding to the myosin rather than by the Ca2+ dependent modification of the phosphorylated state of the myosin (Kohama, K., and Kendrick-Jones, J. (1986) J. Biochem. (Tokyo) 99, 1433-1446). Ca2+-binding light chain (CaLC) has been suggested to be primary importance in this Ca2+ inhibition (Kohama, K., Takano-Ohmuro, H., Tanaka, T., Yamaguchi, T., and Kohama, T. (1986) J. Biol. Chem. 261, 8022-8027). The amino acid sequence of CaLC was determined; it was composed of 147 amino acid residues and the N terminus was acetylated. The molecular weight was calculated to be 16,131. The homology of CaLC in the amino acid sequence with 5,5'-dithiobis-(2-nitrobenzoic acid) light chain and alkali light chain of skeletal muscle myosin were rather low, i.e., 25% and 30%, respectively. Interestingly, however, the CaLC sequence was 40% homologous with brain calmodulin. This amino acid sequence was confirmed by sequencing the cloned phage DNA accommodating cDNA coding CaLC. Northern and Southern blot analysis indicated that 0.8-kilobase pair mRNA was transcribed from a single CaLC gene. This is the first report on the amino acid sequence of myosin light chain of lower eukaryotes and nucleotide sequence of its mRNA. PMID- 3335499 TI - Isolation and characterization of Chinese hamster ovary cell mutants deficient in acyl-coenzyme A:cholesterol acyltransferase activity. AB - A protocol has been developed for isolating cholesterol ester-deficient cells from the Chinese hamster ovary cell clone 25-RA. This cell line previously was shown to be partially resistant to suppression of cholesterogenic enzyme activities by 25-hydroxycholesterol and to accumulate a large amount of intracellular cholesterol ester when grown in medium containing 10% fetal calf serum (Chang, T. Y., and Limanek, J. S. (1980) J. Biol. Chem. 255, 7787-7795). The higher cholesterol ester content of 25-RA is due to an increase in the rate of cholesterol biosynthesis and low density lipoprotein receptor activity compared to wild-type Chinese hamster ovary cells, and not due to an abnormal acyl-CoA:cholesterol acyltransferase enzyme. The procedure to isolate cholesterol ester-deficient mutants utilizes amphotericin B, a polyene antibiotic known to bind to cholesterol and to form pore complexes in membranes. After incubation in cholesterol-free medium plus an inhibitor of endogenous cholesterol biosynthesis, 25-RA cells were found to be 50-500 times more sensitive to amphotericin B killing than were mutant cells containing reduced amounts of cholesterol ester. Twelve amphotericin B-resistant mutants were isolated which retained the 25 hydroxycholesterol-resistant phenotype. These mutants did not exhibit the perinuclear lipid droplets characteristic of 25-RA cells, and lipid analysis revealed a large (up to 40-fold) reduction in cellular cholesterol ester. The acyl-CoA:cholesterol acyltransferase activities of these cholesterol ester deficient mutants were markedly lower than 25-RA when assayed in intact cells or in an in vitro reconstitution assay. The tightest mutant characterized, AC29, was found to have less than 1% of the parental acyl-CoA:cholesterol acyltransferase activity. These mutants all have reduced rates of sterol synthesis and lower low density lipoprotein receptor activity compared to 25-RA, probably as a consequence of their reduced enzyme activities. Cell fusion experiments revealed that the phenotypes of all the mutants examined are not dominant and that the mutants all belong to the same complementation group. We conclude that these mutants contain a lesion in the gene encoding acyl-CoA:cholesterol acyltransferase or in a gene encoding a factor needed for enzyme production. PMID- 3335501 TI - Bovine protamine genes contain a single intron. The structures of the two alleles. AB - In a recent paper, we described the isolation of the first bovine protamine cDNA (BPK59), demonstrating that the gene was autosomal and single copy (Krawetz, S. A., Connor, W., and Dixon, G. H. (1987) DNA 6, 45-57). We have since utilized the BPK59 clone as a probe, to isolate both alleles of the protamine gene from a bovine genomic library constructed in Charon 28. The sequenced alleles are highly homologous and code for identical mRNAs. Unlike the trout protamine genes, the bovine gene is not contiguous as it possesses a single intron. This intron divides the highly variable mammalian carboxyl domain from the conserved protamine basic core. Three tandemly repeated CG-like ("enhancer") sequences upstream from the CAAT box have been identified, separated by a conserved spacer region. Their possible role in the transcription of this P1 gene is discussed. The bovine genome immediately surrounding (approximately equal to 20 kilobase pairs) the protamine gene has been mapped and reveals that the sequence flanking the 5' segment of the gene is unique, while the sequence flanking the 3' segment is repetitive. PMID- 3335502 TI - Purification and characterization of 3-hydroxyisobutyrate dehydrogenase from rabbit liver. AB - 3-Hydroxyisobutyrate dehydrogenase (3-hydroxy-2-methyl propanoate: NAD+ oxidoreductase, EC 1.1.1.31) was purified 1800-fold from rabbit liver by detergent extraction, differential solubility in polyethylene glycol and (NH4)2SO4, and column chromatography on DEAE-Sephacel, phenyl-Sepharose, CM(carboxymethyl)-Sepharose, Affi-Gel Blue, and Ultrogel AcA-34. The enzyme had a native Mr of 74,000 and appeared to be a homodimer with subunit Mr = 34,000. The enzyme was specific for NAD+. It oxidized both S-3-hydroxyisobutyrate and R-3 hydroxyisobutyrate, but the kcat/Km was approximately 350-fold higher for the S isomer. Steady state kinetic analysis indicates an ordered Bi Bi reaction mechanism with NAD+ binding before 3-hydroxyisobutyrate. The enzyme catalyzed oxidation of S-3-hydroxyisobutyrate between pH 7.0 and 11.5 with optimal activity between pH 9.0 and 11.0. The enzyme apparently does not have a metal ion requirement. Essential sulfhydryl groups may be present at both the 3 hydroxyisobutyrate and NAD+ binding sites since inhibition by sulfhydryl-binding agents was differentially blocked by each substrate. The enzyme is highly sensitive to product inhibition by NADH which may play an important physiological role in regulating the complete oxidation of valine beyond the formation of 3 hydroxyisobutyrate. PMID- 3335503 TI - Human cytosolic thymidine kinase. Purification and physical characterization of the enzyme from HeLa cells. AB - The mammalian cytosolic thymidine kinase is one of a number of enzymes involved in DNA replication whose activities increase dramatically during S phase of the cell cycle. As a first step in defining the mechanisms that control the S phase induction of thymidine kinase activity, we have purified the human enzyme from HeLa cells and raised a specific immune serum against the purified protein. The enzyme was isolated from cells arrested in S phase by treatment with methotrexate and purified to near homogeneity by ion-exchange and affinity chromatography. Stabilization of the purified enzyme was achieved by the addition of digitonin. An electrophoretic Rm of 0.2 in nondenaturing gels characterizes the purified enzyme activity as cytosolic thymidine kinase. The enzyme has a Stoke's radius of 40 A determined by gel filtration and a sedimentation coefficient of 5.5 S determined by glycerol gradient sedimentation. Based on these hydrodynamic values, a native molecular weight of 96,000 was calculated for the purified enzyme. When electrophoresed in denaturing sodium dodecyl sulfate-polyacrylamide gels under reducing conditions, the most purified enzyme fraction was found to contain one predominant polypeptide of Mr = 24,000. Several lines of evidence indicate that this polypeptide is responsible for thymidine kinase enzymatic activity. 1) The Mr = 24,000 polypeptide co-migrates with thymidine kinase activity in electrophoretic and sedimentation analyses. 2) A subunit Mr = 25,504 is predicted by the nucleotide sequence of a recently isolated cDNA clone that encodes HeLa thymidine kinase. 3) Mouse LTK- cells transformed with this clone express a cytosolic thymidine kinase activity, as well as a novel Mr = 24,000 polypeptide detectable with immune serum raised against the purified human enzyme. PMID- 3335504 TI - Characterization of antisera to a synthetic carboxyl-terminal peptide of the glucose transporter protein. AB - Peptides corresponding to amino acid residues 1-12 of the amino terminal and 480 492 of the carboxyl terminal of the deduced sequence of the glucose transporter were synthesized and used to produce site-specific polyclonal antipeptide sera. In a solid-phase radioimmunoassay, antiserum to the carboxyl terminal recognizes peptide 480-492 and purified human erythrocyte glucose transporter, but not peptide 1-12. Antiserum to the amino terminal recognizes peptide 1-12 but neither peptide 480-492 nor the erythrocyte transporter. The antiserum to the carboxyl terminal specifically immunoblots the Mr 55,000 glucose transporter in erythrocyte membranes and the purified erythrocyte transporter. It also recognizes a Mr 40,000-60,000 polypeptide in membranes of cells derived from different mammalian species and tissues including insulin-sensitive rat adipocytes as well as a Mr 20,000 tryptic fragment of the transporter which contains the site for photolabeling by cytochalasin B. Antiserum to the carboxyl terminal of the transporter binds specifically to leaky erythrocyte membranes but not to intact erythrocytes. This binding is saturable and competitively inhibited by peptide 480-492. Using immunofluorescence microscopy, this antiserum detects glucose transporter protein in permeabilized erythrocytes, but not in intact erythrocytes. These studies provide immunochemical evidence in support of the predicted cytoplasmic orientation of the carboxyl terminus of the glucose transporter, allow us to suggest a spatial relationship of the cytochalasin B binding site to the carboxyl terminal of the glucose transporter and suggest that antisera directed to the carboxyl terminal domain of the protein may be useful for the immunocytochemical localization of the glucose transporter. PMID- 3335505 TI - In vivo binding of retinol to chromatin. The binding is mediated by a lipoprotein. AB - We have previously shown that exposure of responding cells to vitamin A leads to profound modifications of chromatin structure as revealed by an increased susceptibility to DNase I digestion, modified patterns of histone acetylation, and impaired synthesis of a nonhistone chromosomal protein (Ferrari, N., and Vidali, G. (1985) Eur. J. Biochem. 151, 305-310). The present results show that these effects are most probably due to the direct interaction between retinol and chromatin, and analysis of mononucleosomes and higher oligomers obtained from retinol-treated cells shows that retinol is indeed tightly bound to chromatin. Enzymatic digestions of vitamin A containing nucleosomes with proteinase K, phospholipase C, and phospholipase A2 support a model where the final binding of retinol to chromatin is mediated by a lipoprotein: the recognition of the binding sites on DNA being dictated by the proteic component while the hydrophobic retinol is solubilized in the fatty acid moiety. PMID- 3335506 TI - DNA repair synthesis in human fibroblasts requires DNA polymerase delta. AB - When UV-irradiated cultured diploid human fibroblasts were permeabilized with Brij-58 then separated from soluble material by centrifugation, conservative DNA repair synthesis could be restored by a soluble factor obtained from the supernatant of similarly treated HeLa cells. Extensive purification of this factor yielded a 10.2 S, 220,000-dalton polypeptide with the DNA polymerase and 3'- to 5'-exonuclease activities reported for DNA polymerase delta II (Crute, J. J., Wahl, A. F., and Bambara, R. A. (1986) Biochemistry 25, 26-36). Monoclonal antibody to KB cell DNA polymerase alpha, while binding to HeLa DNA polymerase alpha, did not bind to the HeLa DNA polymerase delta. Moreover, at micromolar concentrations N2-(p-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate (BuPdGTP) and 2-(p-n-butylanilino)-2'-deoxyadenosine 5'-triphosphate (BuAdATP) were potent inhibitors of DNA polymerase alpha, but did not inhibit the DNA polymerase delta. Neither purified DNA polymerase alpha nor beta could promote repair DNA synthesis in the permeabilized cells. Furthermore, under conditions which inhibited purified DNA polymerase alpha by greater than 90%, neither monoclonal antibodies to DNA polymerase alpha, BuPdGTP, nor BuAdATP was able to inhibit significantly the DNA repair synthesis mediated by the DNA polymerase delta. Thus, it appears that a major portion of DNA repair synthesis induced by UV irradiation might be catalyzed by DNA polymerase delta. When xeroderma pigmentosum human diploid fibroblasts were utilized, DNA repair synthesis dependent upon ultraviolet light could be restored by addition of both T4 endonuclease V and DNA polymerase delta, but not by addition of either one alone. This result suggests that cytosol depleted permeabilized DNA repair-defective human fibroblasts and HeLa DNA polymerase delta might be exploited to provide a functional assay for purifying active DNA repair factors from DNA repair-proficient cells without a preknowledge of their function. PMID- 3335507 TI - Solubilization of the functional C5a receptor from human polymorphonuclear leukocytes. AB - The C5a receptor has been extracted in an active state from the membranes of human polymorphonuclear leukocytes with the detergents digitonin and beta-dodecyl maltoside. The solubilized receptor exhibits a single class of high affinity binding sites with a Kd = 90 pM, a value similar to that found with intact membranes. Physical studies with the soluble receptor demonstrate that it exists in two forms which differ in molecular mass. Gel filtration experiments with receptor to which C5a has been bound give an apparent molecular mass for the complex of 150-200 kDa. When the experiments were repeated with nonliganded receptor, most of the C5a binding activity eluted with an apparent mass of 150 200 kDa. However, the peak had a pronounced trailing shoulder indicating that, in the nonliganded state, a portion of the receptor population exists in a smaller form, which may be converted to the larger form on binding C5a. The molecular mass of the smaller form, estimated to be 30-70 kDa, is consistent with that of the binding subunit of the receptor. These data imply that the larger form, and therefore the bulk of the solubilized receptor, is oligomeric, a conclusion which is supported by cross-linking studies. When C5a was cross-linked to the soluble receptor two specific complexes with molecular masses of 52 and 95 kDa were formed. The former is the covalent adduct of C5a and the binding subunit of the receptor and the latter appears to be a complex between the 52-kDa species and an additional polypeptide. PMID- 3335509 TI - Hepatic mitochondrial cytochrome P-450 system. Identification and characterization of a precursor form of mitochondrial cytochrome P-450 induced by 3-methylcholanthrene. AB - Hepatic mitoplasts from 3-methylcholanthrene-treated rats contain cytochrome P 450 which can metabolize polycyclic aromatic hydrocarbons like benzo(a)pyrene. Mitochondrial cytochrome P-450 was partially purified and reconstituted in vitro using adrenodoxin and the adrenodoxin reductase electron transfer system and [3H]benzo(a)pyrene as the substrate. A polyclonal antibody to purified microsomal P-450c (a major 3-methylcholanthrene-inducible form) inhibited the activity of mitochondrial enzyme in a concentration-dependent manner and also reacted with a 54-kDa protein on the immunoblots. A monoclonal antibody having exclusive specificity for P-450c, on the other hand, did not inhibit the aryl hydrocarbon hydroxylase activity of the mitochondrial enzyme and showed no detectable cross reaction with the 54-kDa mitochondrial protein. Similarly, two-dimensional analysis and immunodetection using the polyclonal antibody showed distinct molecular properties of the mitochondrial enzyme different from the similarly induced microsomal P-450c with respect to the isoelectric pH. In vitro translation of free polysomes from 3-methylcholanthrene-induced liver, transport of precursor proteins by isolated mitochondria in vitro, and immunoprecipitation with the polyclonal antibody showed the presence of a 57-kDa putative precursor which is transported and processed into mature 54-kDa species. These results present evidence for the true intramitochondrial location of the P-450c-antibody reactive isoform detected in 3-methylcholanthrene-induced rat liver mitochondria. PMID- 3335508 TI - The structure of human complement component C7 and the C5b-7 complex. AB - The molecular architecture of human complement component C7 was elucidated at several structural levels. The complete primary structure of C7 was derived from the cDNA sequence of clones isolated from a human liver library. C7 is a mosaic protein that consists of 821 amino acids. The amino-terminal two-thirds of C7 has 23-30% homology with complement components C8 and C9. In addition, the carboxyl terminal third contains four cysteine-rich segments that have overlapping internal homology. The protein is a single polypeptide chain with 28 disulfide bonds and is glycosylated at two sites. Virtually all the cysteines are found in small units of 35-77 amino acids that exhibit homology with those of various proteins including the low density lipoprotein receptor, epidermal growth factor precursor, thrombospondin, and blood coagulation factors IX and X. The secondary structural analysis, estimated by circular dichroism, suggested a high content of beta-sheet (38%) and beta-turns (24%). The tertiary structure, visualized by transmission electron microscopy, indicated a flexible elongated molecule with dimensions of 151 X 59 X 43 A. The quaternary structure of the C5b-7 complex bound to lipid vesicles was observed to be in the form of monomers or dimers. The monomer C5b-7 consists of a leaflet and a long flexible stalk, and the dimer has two leaflets linked through a supercoiled stalk. Membrane binding is mediated by the stalk part of the complexes. Using a radioiodinated photoreactive cross linking reagent bound to the polar head group of phosphatidylethanolamine, the stalk part of the C5b-7 complex could be labeled preferentially, and it was found to consist mainly of C6 and C7. Thus, C7 plays a major role in bringing about the hydrophilic-amphiphilic transition during the formation of the membrane attack complex, and it serves as a membrane anchor for the C5b-7 complex. PMID- 3335511 TI - Differential stereoselectivity on metabolism of triphenylene by cytochromes P-450 in liver microsomes from 3-methylcholanthrene- and phenobarbital-treated rats. AB - Metabolism of triphenylene by liver microsomes from control, phenobarbital(PB) treated rats and 3-methylcholanthrene(MC)-treated rats as well as by a purified system reconstituted with cytochrome P-450c in the absence or presence of purified microsomal epoxide hydrolase was examined. Control microsomes metabolized triphenylene at a rate of 1.2 nmol/nmol of cytochrome P-450/min. Treatment of rats with PB or MC resulted in a 40% reduction and a 3-fold enhancement in the rate of metabolism, respectively. Metabolites consisted of the trans-1,2-dihydrodiol as well as 1-hydroxytriphenylene, and to a lesser extent 2 hydroxytriphenylene. The (-)-1R,2R-enantiomer of the dihydrodiol predominated (70 to 92%) under all incubation conditions. Incubation of racemic triphenylene 1,2 oxide with microsomal epoxide hydrolase produced dihydrodiol which was highly enriched (80%) in the (-)-1R,2R-enantiomer. Experiments with 18O-enriched water showed that attack of water was exclusively at the allylic 2-position of the arene oxide, indicating that the 1R,2S-enantiomer of the oxide was preferentially hydrated by epoxide hydrolase. Thiol trapping experiments indicated that liver microsomes from MC-treated rats produced almost exclusively (greater than 90%) the 1R,2S-enantiomer of triphenylene 1,2-oxide whereas liver microsomes from PB treated rats formed racemic oxide. The optically active oxide has a half-life for racemization of only approximately 20 s under the incubation conditions. This study may represent the first attempt to address stereochemical consequences of a rapidly racemizing intermediary metabolite. PMID- 3335510 TI - cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal). AB - In hyaline membrane disease of premature infants, lack of surfactant leads to pulmonary atelectasis and respiratory distress. Hydrophobic surfactant proteins of Mr = 5,000-14,000 have been isolated from mammalian surfactants which enhance the rate of spreading and the surface tension lowering properties of phospholipids during dynamic compression. We have characterized the amino terminal amino acid sequence of pulmonary proteolipids from ether/ethanol extracts of bovine, canine, and human surfactant. Two distinct peptides were identified and termed SPL(pVal) and SPL(Phe). An oligonucleotide probe based on the valine-rich amino-terminal amino acid sequence of SPL(pVal) was utilized to isolate cDNA and genomic DNA encoding the human protein, termed surfactant proteolipid SPL(pVal) on the basis of its unique polyvaline domain. The primary structure of a precursor protein of 20,870 daltons, containing the SPL(pVal) peptide, was deduced from the nucleotide sequence of the cDNAs. Hybrid-arrested translation and immunoprecipitation of labeled translation products of human mRNA demonstrated an Mr = 22,000 precursor protein, the active hydrophobic peptide being produced by proteolytic processing to Mr = 5,000-6,000. Two classes of cDNAs encoding SPL(pVal) were identified. mRNA of approximately 900 bases was identified on Northern analysis of fetal and adult RNA. Human SPL(pVal) mRNA was more abundant in the adult than in fetal lung. The SPL(pVal) gene locus was assigned to chromosome 8. PMID- 3335512 TI - Characterization of rat Leydig cell gonadotropin receptor structure by affinity cross-linking. AB - The present study was intended to examine the structure of the rat Leydig cell gonadotropin receptor. Leydig cell suspensions were prepared by either collagenase digestion or mechanical disruption of the testes. The cells were incubated with 125I-human chorionic gonadotropin (hCG) following which the bound 125I-hCG was covalently cross-linked to the cell surface receptor using a cleavable (dithiobis(succinimidyl propionate] and a noncleavable (disuccinimidyl suberate) cross-linking reagent. The extracted cross-linked membrane proteins were resolved on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions and subjected to autoradiographic analysis. Under nonreducing conditions, three radiolabeled bands, in addition to intact hCG and its alpha-subunit, were detected with apparent molecular weights of 184,000, 136,000, and 103,000. However, under reducing conditions, three radiolabeled bands migrated on the gel corresponding to molecular weights of 144,000, 106,000, and 75,000. The binding of 125I-hCG to the receptor was inhibited by hCG and luteinizing hormone, but not by a number of other peptides or proteins. The radiolabeled bands were not detectable in hCG down-regulated Leydig cells. Furthermore, a similar autoradiographic pattern of 125I-hCG-linked complexes was seen when the 125I-linked receptor complex was subjected to immunoprecipitation with anti-hCG antibodies followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition, evidence was obtained indicating that these three labeled bands were derived from the same molecular species. The data suggests that the hCG receptor in Leydig cell is probably an oligomeric complex with a molecular weight of about 250,000, which is composed of three polypeptide chains of molecular weights 121,000, 83,000, and 52,000 held together through noncovalent forces. Additionally, collagenase treatment of Leydig cells does not appear to alter the autoradiographic pattern of the 125I-hCG-linked receptor. PMID- 3335514 TI - Sulfated proteoglycans and sulfated proteins in guinea pig megakaryocytes and platelets in vivo. Relevance to megakaryocyte maturation and platelet activation. AB - This study has examined changes in proteoglycan synthesis during megakaryocyte maturation in vivo. Guinea pigs were injected with Na235SO4, and megakaryocytes and platelets were isolated from 3 h to 5 days later. The proteoglycans and other sulfated molecules in both cells were characterized at each time point by gel filtration, ion-exchange chromatography, gel electrophoresis, and chemical and enzymatic digestions. Two populations of chondroitin 6-sulfate proteoglycans were found by DEAE-Sephacel chromatography. The major fraction was eluted with 4 M guanidine hydrochloride and the minor fraction with 4 M guanidine HCl, 2% Triton X-100. The Kav of the major proteoglycan peak in the platelets at 1 day after injection was 0.18-0.20 on Sepharose CL-6B and decreased gradually to 0.12 by 3 days, when proteoglycan radioactivity per cell was maximal. The peak for megakaryocyte proteoglycans at 3 h was broad, with Kav = 0.1-0.2. The appearance of different portions of the proteoglycan peak in platelets coincided with their disappearance from megakaryocytes. Proteoglycan size was a function of glycosaminoglycan chain length. The proteoglycans eluted with Triton X-100 from DEAE-Sephacel (Kav = 0.04-0.07 on Sepharose CL-6B) were not labeled in platelets until 2 days after injection. Our data suggest that megakaryocytes synthesize different-sized chondroitin sulfate proteoglycans at different stages of development. The proteoglycans of the major fraction were released from platelets in response to thrombin, and a small amount was released by ADP. The proteoglycans of the Triton X-100 eluate were not released by thrombin or ADP. About 20% of the sulfate radioactivity was incorporated into molecules that appear to be sulfated proteins and were not released by thrombin or ADP. PMID- 3335513 TI - Biosynthesis and cell-free translation of Swarm rat chondrosarcoma and bovine cartilage link proteins. AB - In cartilage, link protein(s) (LP) stabilize proteoglycan aggregates via their specific association with hyaluronic acid and proteoglycan monomers. Two major link glycoproteins are produced in bovine articular cartilage, designated LP1 (49.5 kDa) and LP2 (44.0 kDa), whereas rat chondrosarcoma produces a single link protein species similar in size to bovine LP2. Although multiple link proteins differ to a significant degree in carbohydrate content, it is not known whether they arise from variable glycosylation of a single common protein core or from complete glycosylation of different protein cores. Biosynthesis of these molecules has been studied under conditions where differences generated by N linked glycosylation would not be evident. Link proteins were immunoprecipitated 1) from cell-free translation products of total cellular and size fractionated RNA and 2) from cell lysates and medium of cultured chondrocytes using short term radioactive labeling of the protein in the presence and absence of tunicamycin. A 42-kDa link protein precursor is synthesized by cell-free translation of either rat chondrosarcoma or bovine chondrocyte mRNa. An apparently single 41.5-kDa link protein is synthesized with inhibition of N-linked glycosylation by tunicamycin, whereas LP1 and LP2 are the mature products of cultured bovine chondrocytes. The size range of translatable rat chondrosarcoma LP mRNA is 4.0-5.5 kilobase pairs and bovine LP mRNA is 3.0-4.5 kilobase pairs, both much larger than required to encode the link protein molecule. These results suggest that a single link protein precursor gives rise to multiple fully glycosylated forms and that link protein is not synthesized as a significantly larger "pro" form. PMID- 3335515 TI - Juvenile hormone regulation of mRNA levels for a highly abundant hemolymph protein in larval Trichoplusia ni. AB - Several hemolymph proteins ranging in size from 73 to 76 kDa increase to very high levels just prior to metamorphosis in Trichoplusia ni (Lepidoptera). One of these proteins (pI = 5.8, Mr = 76,000) was selected for a study of hormonal regulation. The appearance of this protein could be suppressed in vivo by topical treatment with the juvenile hormone analog fenoxycarb. An antiserum for this protein was prepared and shown to react selectively with the 76-kDa protein in whole hemolymph. Translation of poly(A)-containing RNA from untreated larvae yielded the 76-kDa protein, whose identity was verified with the antibody, whereas mRNA from juvenile hormone analog-treated larvae did not. These data indicate that juvenile hormone acts to regulate the level of the mRNA of this hemolymph protein. PMID- 3335516 TI - Complete processing of a small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase from pea requires the amino acid sequence Ile-Thr-Ser. AB - Chloroplast import and processing of two precursor proteins with mutations in the carboxyl-terminal region of the transit peptide were examined in vitro. Deletion mutations were introduced into the 57-amino acid transit peptide of a chloroplast protein, the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, from pea. A mutant, PSd48/57, in which nine carboxyl-terminal amino acids of the transit peptide had been deleted, was imported and processed to a series of 13- to 18-kDa polypeptides including the 14-kDa mature small subunit. In contrast, processing of a mutant, PSd45/57, in which an additional three amino acids had been removed, resulted in a series of polypeptides which did not include the mature small subunit. Whereas PSd48/57 was imported as efficiently as the wild type precursor, import of PSd45/57 was only 25% as efficient as that of the authentic precursor. The mutant precursor proteins PSd48/57 and PSd45/57 are distinguished by a three-amino acid sequence, Ile-Thr-Ser, located in the carboxyl-terminal region of the transit peptide. We show that all or part of this sequence is required for correct processing. PMID- 3335517 TI - Association of deoxyribonuclease I with the pointed ends of actin filaments in human red blood cell membrane skeletons. AB - We have characterized the interaction of bovine pancreatic deoxyribonuclease I (DNase I) with the filamentous (F-)actin of red cell membrane skeletons stabilized with phalloidin. The hydrolysis of [3H]DNA was used to assay DNase I. We found that DNase I bound to a homogenous class of approximately equal to 2.4 X 10(4) sites/skeleton with an association rate constant of approximately 1 X 10(6) M-1 S-1 and a KD of 1.9 X 10(-9) M at 20 degrees C. Phalloidin lowered the dissociation constant by approximately 1 order of magnitude. The DNase I which sedimented with the skeletons was catalytically inactive but could be reactivated by dissociation from the actin. Actin and DNA bound to DNase I in a mutually exclusive fashion without formation of a ternary complex. Phalloidin-treated red cell F-actin resembled rabbit muscle G-actin in all respects tested. Since the DNase I binding capacity of the skeletons corresponded to the number of actin protofilaments previously estimated by other methods, it seemed likely that the enzyme binding site was confined to one end of the filament. We confirmed this premise by showing that elongating the red cell filaments with rabbit muscle actin monomers did not appreciably add to their capacity to bind or inhibit DNase I. Saturation of skeletons with cytochalasin D or gelsolin, avid ligands for the barbed end of actin filaments, did not reduce their binding of DNase I. Furthermore, neither cytochalasin D nor DNase I alone blocked all of the sites for addition of monomeric pyrene-labeled rabbit muscle G-actin to phalloidin treated skeletons; however, a combination of the two agents did so. In the presence of phalloidin, the polymerization of 300 nM pyrenyl actin on nuclei constructed from 5 nM gelsolin and 25 nM rabbit muscle G-actin was completely inhibited by 35 nM DNase I but not by 35 nM cytochalasin D. We conclude that DNase I associates uniquely with and caps the pointed (slow-growing or negative) end of F-actin. These results imply that the amino-terminal, DNase I-binding domain of the actin protomer is oriented toward the pointed end and is buried along the length of the actin filament. PMID- 3335519 TI - Quaternary interactions in hemoglobin beta subunit tetramers. Kinetics of ligand binding and self-assembly. AB - We have investigated the rates of monomer in equilibrium with tetramer self association of oxygenated beta SH subunits of human hemoglobin A as well as the influence of self-association on the binding kinetics for O2 and CO. A 4 beta in equilibrium with 2 beta 2 in equilibrium with beta 4 assembly pathway can be used to describe the association equilibria and kinetics. We have determined all four elementary rate constants for this assembly pathway at 15 degrees C in 0.1 M Tris HCl, 0.1 M NaCl, 1 mM Na2EDTA, pH 7.4. These data imply that a significant amount (approximately 17%) of beta 2 can be present. Laser photolysis kinetic studies of O2 binding indicate that the O2 association rate constant is unaffected by the degree of self-association. In contrast, photolysis of beta CO solutions shows an overall rate of CO binding that increases at higher protein concentrations. These data are consistent with a concentration-dependent equilibrium between two protein species with CO association rates differing by a factor of 2.5, but they do not appear to be compatible with a direct assignment of different CO binding rates to the different assembly states. Rather, we believe the data imply that CO binding to beta oligomers is heterogeneous, with both a fast binding and a slow binding form being present in single association states. The fast binding form predominates (approximately equal to 87%) in beta 4, while the beta monomer has very little or none of the fast binding form. We propose that the slow binding component within beta 4 may be those subunits with rotationally disordered hemes (La Mar, G. N., Yamamoto, Y., Jue, T., Smith, K. M., and Pandey, R. K. (1985) Biochemistry 24, 3826-3831). The implications of these findings for the use of isolated subunits as models for the subunits within "R state" hemoglobin tetramers are discussed. PMID- 3335518 TI - Demonstration of the ascorbate dependence of membrane-bound dopamine beta monooxygenase in adrenal chromaffin granule ghosts. AB - Chromaffin granule ghosts from bovine adrenal medullae have been used to examine the ability of membrane-bound dopamine beta-monooxygenase to interact directly with intravesicular ascorbate and to investigate vectorial electron transfer from external ascorbate across the ghost membrane. Ghosts prepared by a modification of published procedures were shown to be fully active in both dopamine uptake and norepinephrine production. Dopamine uptake is dependent on the presence of a magnesium and ATP ionic complex, is abolished by reserpine, and reaches a steady state level in the presence of dopamine beta-monooxygenase, ascorbate, catalase, and fumarate. Omission of ascorbate either inside or outside the ghosts greatly enhances dopamine accumulation, which reaches levels of approximately 30 nmol/mg under these conditions. Correspondingly, in the presence of all components, norepinephrine production reached approximately 100 nmol/mg in 30 min of incubation. Norepinephrine production was strictly magnesium-ATP-dependent, inhibited by either reserpine or dopamine beta-monooxygenase inactivation, and was markedly reduced when ascorbate was omitted from either inside or outside the ghosts. In the presence of limiting amounts of internal ascorbate, rapid norepinephrine production occurred which corresponded to the amount of initial ascorbate present, followed by a much slower endogenous norepinephrine production observable after complete depletion of internal ascorbate. The endogenous rate of norepinephrine production likely represents epinephrine-supported dopamine beta monooxygenase turnover. Taken together, the data demonstrate that facile norepinephrine production by membrane-bound dopamine beta-monooxygenase occurs only when internal ascorbate is present, terminates upon depletion of internal ascorbate, and can only be sustained at a significant rate when reducing equivalents from external ascorbate are available. PMID- 3335520 TI - Botulinum C2 toxin ADP-ribosylates cytoplasmic beta/gamma-actin in arginine 177. AB - Isolated cytoplasmic actin of human platelet and pig liver actin, but not rabbit skeletal muscle actin, was ADP-ribosylated by botulinum C2 toxin in the presence of [32P]NAD. Tryptic digestion of the [32P]ADP-ribosylated platelet actin generated two labeled peptides: a soluble peptide covering residues 174-183 and an insoluble fragment containing residues 148-183. Further digestion of these two peptides with thermolysin yielded the same radioactive peptide, which was in both cases peptide 175-177. Amino acid sequence analysis of peptides 174-183 and 175 177 located the ADP-ribosylation on Arg177. PMID- 3335521 TI - Complementary DNA cloning of cytochrome P-450s related to P-450(M-1) from the complementary DNA library of female rat livers. Predicted primary structures for P-450f, PB-1, and PB-1-related protein with a bizarre replacement block and their mode of transcriptional expression. AB - Three kinds of cDNA clones were isolated from a cDNA library synthesized from female rat liver mRNA by cross-hybridization with the P-450(M-1) cDNA as a probe and sequenced. One clone appears to be the previously isolated P-450f cDNA clone with an additional 5'-untranslated and coding sequence which are lacking in the previously reported clone (Gonzalez, F. J., Kimura, S., Song, B.-J., Pastewka, J., Gelboin, H. V., and Hardwick, J. P. (1986) J. Biol. Chem. 261, 10667-10672), though several nucleotide differences were seen. Another one is for P-450PB-1 mRNA previously isolated, and the last has an almost identical nucleotide sequence to P-450PB-1 (the same report cited above) except for one region of 159 base pairs where the sequence homology between the two is abruptly broken down. This nonhomologous region appears to correspond exactly to the entire eighth exon, estimated by comparison with the gene structure of the related P-450 (P 450(M-1)). This replacement in P-450PB-1 (ps) causes a frameshift in the open reading frame, resulting in the generation of a truncated form of P-450 with a strange replacement block and lacking the heme-binding region. This observation suggests that the mRNA whose cDNA was cloned here was produced from a recombinant gene generated by gene conversion or from alternative splicing of a cryptic exon. Sex- and age-dependent expression of the mRNAs investigated by dot blot analysis revealed that normal- and pseudo-type PB-1 mRNA were expressed in both male and female rat livers, though their age-dependent expression was different in male and female animals. In addition, both the mRNAs were specifically expressed in the female brain of 8 weeks, whereas practically no expression was observed in kidney and lung of both sexes. PMID- 3335522 TI - Binding properties of a mannose-specific lectin from the snowdrop (Galanthus nivalis) bulb. AB - Carbohydrate binding properties of a new plant lectin (GNA) isolated from snowdrop bulbs were studied using the technique of quantitative precipitation, hapten inhibition, and affinity chromatography on immobilized lectin. Purified GNA precipitated highly branched yeast mannans but did not react with most glucans. Hapten inhibition experiments showed that D-mannose is an inhibitor of GNA-mannan interaction but neither N-acetyl-D-mannosamine nor D-glucose is an inhibitor. Hapten inhibition with various sugars showed that GNA requires the presence of equatorial hydroxyl groups at the C-3 and C-4 positions and an axial group at the C-2 position of the D-pyranose ring. A nonreducing terminal D mannose residue is necessary for the interaction of oligosaccharides, and oligosaccharides with terminal Man(alpha-1-3)Man units showed the highest inhibitory potency (10-30 times greater than D-mannose) among the manno oligosaccharides tested. The presence of the hydrophobic p-nitrophenyl aglycone increased the affinity of D-mannose only slightly. Immobilized GNA bound yeast mannan but did not bind glycogen. The behavior of glycoproteins with high mannose type glycan chains depended on the density and the structure of their glycan chains. Glycopeptides which carry Man(alpha 1-3)Man units were retarded on the immobilized GNA column whereas those lacking this unit or with hybrid type glycan chains were not retarded on the column. PMID- 3335523 TI - Isolation and sequence analysis of the glycosaminoglycan attachment site of type IX collagen. AB - Type IX collagen from chick embryonic cartilage is unique among the collagens in that it contains chondroitin sulfate covalently linked to the alpha 2(IX) polypeptide chain. We have isolated and sequenced the glycosaminoglycan containing peptide released by collagenase digestion from type IX collagen, labeled biosynthetically with [35SO4] and 3H-aminoacids. This peptide was purified by gel filtration and, following chondroitinase ABC digestion, by reverse-phase high performance liquid chromatography. The amino acid sequence obtained for this peptide has 23 residues, beginning and ending with a collagenous sequence, indicating that it spans an internal noncollagenous domain. Comparison of this sequence with the one predicted from cDNA clone pYN 1738 for the alpha 1(IX)chain and pYN 1731 and pDM 222 for the alpha 2(IX)chain revealed the peptide to be the noncollagenous NC3 domain of alpha 2(IX). The glycosylated sequence Val-Glu-Gly-Ser*-Ala-Asp- of type IX collagen does not have the Ser-Gly normally functioning as the attachment sequence but does have an acidic residue preceding the serine which should improve the acceptability of this sequence for the xylosyltransferase. That it is an adequate acceptor can be inferred from the observation that type IX collagen carries a glycosaminoglycan chain on over 70% of the molecules isolated. PMID- 3335524 TI - Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma. AB - Much of the tissue damage resulting from trauma to the central nervous system appears to result from secondary, delayed biochemical changes that follow primary mechanical injury. However, the early biochemical events remain to be elucidated. In the present studies, we have used phosphorus (31P) magnetic resonance spectroscopy (MRS) to examine in vivo, the temporal changes in brain intracellular free Mg2+ concentration following fluid percussion head injury in rats. We report that injury caused a profound and rapid decrease in intracellular free Mg2+ which was significantly correlated with the severity of injury. At high levels of injury, the decrease in intracellular free Mg2+ concentration was associated with a decrease in total Mg2+ concentration as determined by atomic absorption spectrophotometry. Prophylactic treatment with MgSO4 prevented the post-traumatic decrease in intracellular free Mg2+ and resulted in a significant improvement in acute neurological outcome. Because magnesium is essential for a number of critical enzyme reactions, including those of glycolysis, oxidative and substrate level phosphorylation, protein synthesis, and phospholipid synthesis, changes in free Mg2+ after brain trauma may represent a critical early factor leading to irreversible tissue damage. PMID- 3335525 TI - The effects of isoproterenol on intracellular calcium concentration. AB - beta-Adrenergic agonist, isoproterenol (ISO), is a potent relaxant of tracheal smooth muscle and inhibits carbachol-induced contraction. The effect of ISO on intracellular free Ca2+ concentration ([Ca2+]i) was examined in bovine tracheal smooth muscle strips, employing aequorin as Ca2+ indicator. Surprisingly, 10 microM ISO induces a 5-fold increase in [Ca2+]i which then gradually declines but still remains higher than basal after 1 h of stimulation. The ISO-induced increase in [Ca2+]i is dose-dependent, and the ED50 is approximately 50 nM. The ISO-induced increase in [Ca2+]i is inhibited by a beta-receptor blocker, propranolol, not by an alpha-blocker, phentolamine. The ISO-induced rise in [Ca2+]i is dependent on extracellular Ca2+. Forskolin, an adenylate cyclase activator, and vasoactive intestinal peptide, which is known to stimulate adenylate cyclase via a specific receptor in this tissue, have similar effects on [Ca2+]i, suggesting that a rise in cyclic AMP concentration mediates this effect of ISO on [Ca2+]i. Pretreatment of muscle with 10 microM ISO inhibits both the initial Ca2+ transient and the contractile response induced by 0.3 microM carbachol. Conversely, in carbachol-pretreated muscle strips, addition of ISO causes a fall rather than a rise in [Ca2+]i, and an inhibition of contraction. These results indicate that ISO has effects on cellular Ca2+ metabolism at more than a single site in bovine tracheal smooth muscle, that these effects are different in control and carbachol-pretreated muscle, and that the relaxing effect of ISO is not due solely to its effect on Ca2+ metabolism. PMID- 3335526 TI - Lipid-induced changes in the secondary structure of snake venom cardiotoxins. AB - The secondary structures of three snake venom cardiotoxins (from Hemachatus hemachatus, Naja naja atra, and Naja naja naja), in aqueous solution and in a lipid-bound form, were investigated by Fourier-transform infrared spectroscopy. The conformation-sensitive protein infrared bands in the amide I region were analyzed using deconvolution and band-fitting procedures. The spectra of the three cardiotoxins in aqueous buffer are very similar; they indicate a high content of both antiparallel beta-sheet structure and unordered conformation. Moreover, component bands characteristic of turns can also be identified. The binding of cardiotoxins to bilayers of dimyristoylphosphatidyl-glycerol results in an increased content of a beta-structure at the expense of the nonordered conformation. It is suggested that lipid-induced conformational transitions to a beta-structure, similar to that observed with cardiotoxins, may be operative also in membrane interaction of other proteins and peptides, particularly with those which have a small tendency to form alpha-helices. PMID- 3335527 TI - Brain tissue accumulates 67copper by two ligand-dependent saturable processes. A high affinity, low capacity and a low affinity, high capacity process. AB - We characterized the mechanism of copper accumulation by the brain, using rat hypothalamic tissue slices incubated with 67Cu as a model system. Two ligand dependent saturable processes were discerned: a high affinity, low capacity process and a low affinity, high capacity process. Vo versus [S] for the high affinity process was a hyperbolic function having an apparent Km and Vmax of 6 microM copper and 23 pmol/min/mg protein, respectively. Vo versus [S] for the low affinity process was a sigmoidal function having an "apparent Km" (So5) and maximal velocity at saturating [S] of 40 microM copper and 425 pmol/min/mg protein, respectively. The two processes were similar in that each exhibited: (a) a requirement for complexing of copper for optimal 67Cu accumulation; (b) a broad ligand specificity with respect to amino acids (histidine, cysteine, threonine, glycine) and peptides (Gly-His-Lys, glutathione) and ineffectiveness of albumin in serving as a facilitatory ligand; (c) a requirement for thermic but not metabolic energy. In spite of these similarities, a 50- or 1000-fold molar excess of ligand (histidine) inhibited 67Cu accumulation by the low affinity process by 60 and 85%, respectively, whereas excess histidine facilitated 67Cu accumulation by the high affinity process by 1.6-4-fold. These results are consistent with 1) a carrier-mediated facilitated diffusion, analogous to that of neutral amino acids, as a means of transporting complexed copper into brain tissue, and 2) the existence of two distinct carrier sites interacting in a positive cooperative manner: a high and a low affinity site. PMID- 3335528 TI - Binding of phosphate to F-ADP-actin and role of F-ADP-Pi-actin in ATP-actin polymerization. AB - Our previous work (Carlier, M.-F., and Pantaloni, D. (1986) Biochemistry 25, 7789 7792) had shown that F-ADP-Pi-actin is a major intermediate in ATP-actin polymerization, due to the slow rate of Pi release following ATP cleavage on filaments. To understand the mechanism of ATP-actin polymerization, we have prepared F-ADP-Pi-actin and characterized its kinetic parameters. 32Pi binds to F ADP-actin with a stoichiometry of 1 mol/mol of F-actin subunit and an equilibrium dissociation constant Kpi of 1.5 mM at pH 7.0 Kpi increases with pH, indicating that the H2PO-4 species binds to F-actin. ADP-Pi-actin subunits dissociate much more slowly from filament ends than ADP-actin subunits; therefore, the stability of filaments in ATP is due to terminal ADP-Pi subunits. The slow rate of dissociation of ADP-Pi-actin also explains the decrease in critical concentration of ADP-actin in the presence of Pi reported by Rickard and Sheterline (Richard, J. E., and Sheterline, P. (1986) J. Mol. Biol. 191, 273-280). The effect of Pi on the rate of actin dissociation from filaments is much more pronounced at the barbed end than at the pointed end. Using gelsolin to block the barbed end, we have shown that the two ends are energetically different in the presence of ATP and saturating Pi, but less different than in the absence of Pi. The results are interpreted within a new model for actin polymerization. It is possible that phosphate binding to F-actin can regulate motile events in muscle and nonmuscle cells. PMID- 3335529 TI - Characterization and identification of a pyrazole-inducible form of cytochrome P 450. AB - In vivo administration of the alcohol dehydrogenase inhibitor pyrazole induces a cytochrome P-450 isozyme. The pyrazole-inducible cytochrome P-450 has been purified from rat livers to electrophoretic homogeneity and its biochemical, spectral, and immunological properties characterized. The final preparation had a specific content of 11 nmol of cytochrome P-450/mg of protein. A single band with an apparent molecular weight of 52,000 was observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The absolute spectrum of the isolated pyrazole cytochrome P-450 displayed peaks at 648 and 396 nm, suggestive of a high spin cytochrome. The ethylisocyanide difference spectrum exhibited two maxima, one at 457 nm, the other at 428 nm. Pyrazole and dimethyl sulfoxide produced binding spectra with the purified P-450, with peaks at 425 or 419 nm and troughs at 390 or 386 nm, respectively. K8 values for dimethyl sulfoxide and pyrazole were 21 and 0.04 mM, respectively. The catalytic activity of the pyrazole cytochrome P-450 was elevated with aniline and dimethylnitrosamine (low Km) but not with aminopyrine, benzphetamine, ethoxycoumarin, or ethoxyresorufin as substrates. An antibody against pyrazole cytochrome P-450 recognized a 52,000 molecular weight protein upon reaction with saline microsomes. The intensity of the immunoblot was increased when microsomes isolated from pyrazole, 4 methylpyrazole-, acetone-, or chronic ethanol-treated rats were utilized, but not after phenobarbital or 3-methylcholanthrene treatment. Homology at the amino terminus of 19 amino acids was observed between pyrazole P-450 and the isoniazid inducible P-450j. Based upon the above catalytic, spectral, and immunological properties, it appears that pyrazole induces a form of cytochrome P-450 which is identical to that induced by ethanol and isoniazid. PMID- 3335531 TI - Fibril-forming collagens in lamprey. AB - Five types of collagen with triple-helical regions approximately 300 nm in length were found in lamprey tissues which show characteristic D-periodic collagen fibrils. These collagens are members of the fibril forming family of this primitive vertebrate. Lamprey collagens were characterized with respect to solubility, mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, carboxylmethyl-cellulose chromatography, peptide digestion patterns, composition, susceptibility to vertebrate collagenase, thermal stability, and segment long spacing-banding pattern. Comparison with fibril forming collagens in higher vertebrates (types I, II, III, V, and XI) identified three lamprey collagens as types II, V, and XI. Both lamprey dermis and major body wall collagens had properties similar to type I but not the typical heterotrimer composition. Dermis molecules had only alpha 1(I)-like chains, while body wall molecules had alpha 2(I)-like chains combined with chains resembling lamprey type II. Neither collagen exhibited the interchain disulfide linkages or solubility properties of type III. The conservation of fibril organization in type II/type XI tissues in contrast to the major developments in type I and type III tissues after the divergence of lamprey and higher vertebrates is consistent with these results. The presence of type II and type I-like molecules as major collagens and types V and XI as minor collagens in the lamprey, and the differential susceptibility of these molecules to vertebrate collagenase is analogous to the findings in higher vertebrates. PMID- 3335530 TI - Purification and characterization of two kinds of low molecular weight kininogens from rat (non-inflamed) plasma. One resistant and the second sensitive to rat glandular kallikreins. AB - Two kinds of low molecular weight kininogens (identified as A and B) were isolated from pooled plasma of Sprague-Dawley rats. They show a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence and absence of 2-mercaptoethanol, and the molecular weights are 68,000 for low Mr kininogen A and 73,000 for low Mr kininogen B. Although the molecular weights and amino acid compositions of the low Mr kininogens are similar, rat submaxillary and urinary kallikreins released bradykinin from low Mr kininogen B, whereas low Mr kininogen A was resistant to these enzymes. The COOH-terminal portion of low Mr kininogen A was isolated after cyanogen bromide treatment, and the amino acid sequence of the COOH-terminal 55 residues including the T-kinin (Ile-Ser bradykinin) was determined. The COOH-terminal portion consists of two sequences with substitution of 4 residues. One peptide corresponds to alpha 1-major acute phase protein (Cole, T., Inglis, A. S., Roxburgh, C. M., Howlett, G. J., and Schreiber, G. (1985) FEBS Lett. 182, 57-61) and the other to the TI-kininogen predicted from a cDNA study (Furuto-Kato, S., Matsumoto, A., Kitamura, N., and Nakanishi, S. (1985) J. Biol. Chem. 260, 12054-12059). The results demonstrate that there exist at least two kinds of low Mr kininogens with clearly different function in rat plasma: one of them, low Mr kininogen A, is a precursor of T kinin and is resistant to kallikreins, and the second, low Mr kininogen B, is sensitive to tissue kallikreins and shares properties with bovine and human low Mr kininogens. The results also demonstrate that T-kininogen is a mixture of two isoproteins which correspond to alpha 1-major acute phase protein or TI kininogen, respectively. We could not detect the low Mr kininogen corresponding to the TII-kininogen predicted from the cDNA study of Furuto-Kato et al. PMID- 3335533 TI - Only one 3'-hydroxyl group of ppp5' A2'p5'A2'p5' A (2-5A) is required for activation of the 2-5A-dependent endonuclease. AB - To investigate the relative importance of each of the ribose 3'-hydroxyl groups of 2-5A (ppp5' A2'p5'A2'-p5' A) in determining binding to and activation of the 2 5A-dependent endonuclease (RNase L), the 3'-hydroxyl functionality of each adenosine moiety of 2-5A trimer triphosphate was sequentially replaced by hydrogen. The analog in which the 5'-terminal adenosine was replaced by 3' deoxyadenosine (viz. ppp5'(3'dA)-2'p5' A2'p5' A) was bound to RNase L as well as 2-5A itself and was only 3 times less potent than 2-5A as an activator of RNase L. On the other hand, when the second adenosine unit was replaced by 3' deoxyadenosine (viz. ppp5' A2'p5'(3'dA)2'p5' A), binding to RNase L was decreased by a factor of eight relative to 2-5A trimer and, even more dramatically, there was a 500-1000-fold drop in ability to activate the 2-5A-dependent endonuclease. Finally, when the 3'-hydroxyl substituent was converted to hydrogen in the 2' terminal residue of 2-5A, a significant increase in both binding and activation ability occurred. We conclude that only the 3'-hydroxyl group of the second (from the terminus) nucleotide residue of 2-5A is needed for effective activation of RNase L. PMID- 3335532 TI - The heavy chain of smooth muscle myosin is phosphorylated in aorta cells. AB - The 204-kDa smooth muscle myosin heavy chain (MHC) from rat aorta smooth muscle cells was found to be phosphorylated following isolation of myosin from strips of intact aorta as well as from primary cultures of aorta cells. Two-dimensional maps of the tryptic peptides revealed that the phosphate was confined to only three peptides and gave a similar pattern for the MHC isolated from intact aorta strips and cultured cells. This map was quite different from the phosphopeptide map found for the 196-kDa MHC of nonmuscle myosin isolated from the same cell culture. Smooth muscle MHC purified from primary cell cultures was found to contain approximately 0.7 mol of phosphate/mol of MHC while the nonmuscle MHC contained approximately 0.8 mol of phosphate/mol of MHC. These observations raise the possibility of an additional regulatory mechanism in smooth muscle operating via MHC phosphorylation. PMID- 3335534 TI - Divergence in primary structure between the molecular forms of acetylcholinesterase. AB - We have isolated a COOH-terminal tryptic peptide from the hydrophobic globular (5.6 S) form of Torpedo californica acetylcholinesterase that exhibits divergence in amino acid sequence from the catalytic subunit of the dimensionally asymmetric (17 S + 13 S) enzyme. The divergent peptide could be recovered from the glycophospholipid-modified 5.6 S enzyme only after treatment with phosphatidylinositol-specific phospholipase C. Upon reduction, carboxymethylation with [14C]iodoacetate, and trypsin digestion the resultant peptides were purified by gel filtration followed by high performance liquid chromatography. The high performance liquid chromatography profiles of 14C-labeled cysteine peptides from lipase-treated 5.6 S enzyme revealed unique radioactive peaks which had not been present in digests of the asymmetric form. These peaks all yielded identical amino acid sequences. The difference in chromatographic behavior of the individual peptides most likely reflects heterogeneity in post-translational processing. Gas-phase sequencing and composition analysis are consistent with the sequence: Leu-Leu-Asn-Ala-Thr-Ala-Cys. Composition includes 2-3 mol each of glucosamine and ethanolamine which is indicative of modification by glycophospholipid. Glucosamine is also present in an asparagine-linked oligosaccharide. The two forms of acetylcholinesterase diverge after the threonine residue within this peptide sequence; the hydrophobic form terminates with cysteine whereas the asymmetric form extends for 40 residues beyond the divergence. The locus of divergence and absence of any other amino acid sequence difference suggest that the molecular forms of acetylcholinesterase arise from a single gene by alternative mRNA processing. PMID- 3335535 TI - Quantitation of the effect of L-carnitine on the levels of acid-soluble short chain acyl-CoA and CoASH in rat heart and liver mitochondria. AB - The steady state levels of mitochondrial acyl-CoAs produced during the oxidation of pyruvate, alpha-ketoisovalerate, alpha-ketoisocaproate, and octanoate during state 3 and state 4 respiration by rat heart and liver mitochondria were determined. Addition of carnitine lowered the amounts of individual short-chain acyl-CoAs and increased CoASH in a manner that was both tissue- and substrate dependent. The largest effects were on acetyl-CoA derived from pyruvate in heart mitochondria using either state 3 or state 4 oxidative conditions. Carnitine greatly reduced the amounts of propionyl-CoA derived from alpha-ketoisovalerate, while smaller effects were obtained on the branched-chain acyl-CoA levels, consistent with the latter acyl moieties being poorer substrates for carnitine acetyltransferase and also poorer substrates for the carnitine/acylcarnitine translocase. The levels of acetyl-CoA in heart and liver mitochondria oxidizing octanoate during state 3 respiration were lower than those obtained with pyruvate. The rate of acetylcarnitine efflux from heart mitochondria during state 3 (with pyruvate or octanoate as substrate, in the presence or absence of malate with 0.2 mM carnitine) shows a linear response to the acetyl-CoA/CoASH ratio generated in the absence of carnitine. This relationship is different for liver mitochondria. These data demonstrate that carnitine can modulate the aliphatic short-chain acyl-CoA/CoA ratio in heart and liver mitochondria and indicate that the degree of modulation varies with the aliphatic acyl moiety. PMID- 3335536 TI - Comparative study of the mucin-type sugar chains of human chorionic gonadotropin present in the urine of patients with trophoblastic diseases and healthy pregnant women. AB - Human chorionic gonadotropins (hCGs) highly purified from the urine of patients with trophoblastic diseases and of healthy pregnant women contain approximately four mucin-type sugar chains in one molecule. The structures of these sugar chains were studied comparatively by using a new sensitive method to obtain mucin type sugar chains quantitatively as radioactive oligosaccharides from a small amount of glycoproteins. The mucin-type sugar chains of all hCGs include sialylated and nonsialylated Gal beta 1----3GalNAc and Gal beta 1----4GlcNAc beta 1----6(Gal beta 1----3)GalNAc. In the case of normal hCG and hydatidiform mole hCG, oligosaccharides containing the tetrasaccharide core occupy approximately 10% of the total mucin-type sugar chains. The ratio of the tetrasaccharide containing oligosaccharides is increased prominently to approximately 60% in choriocarcinoma hCG. The proportion in invasive mole hCG was also increased, but less than the proportion of choriocarcinoma hCG. PMID- 3335537 TI - The pH dependence of red cell membrane transport of titratable anions studied by NMR spectroscopy. AB - The effects of varying extracellular pH on the rates of uptake of titratable anions by human erythrocytes under conditions of constant intracellular pH have been determined for a series of highly related anions, the phosphate "analogs." These compounds are simply substituted phosphorus oxyacids, differing in the number and acidity of titratable protons: phosphate (HPO4(2-), pKa 6.8); phosphite (HPO3(2-), pKa 6.4); hypophosphite (H2PO2-); methylphosphonate ((CH3)PO3(2-), pKa 7.4); dimethylphosphinate ((CH3)2PO2-); fluorophosphate [PO3F2 , pKa 4.7); and thiophosphate (HSPO3(2-), pKa 5.5). Suspensions of intact, Cl(-) loaded erythrocytes (intracellular pH, 7.2) were incubated at 37 degrees C in isotonic buffers (pH 4-8) containing 60 mM phosphate analog for specified time intervals, whereupon influx was halted by the addition of 1 mM 4-acetamido-4' isothiocyanatostilbene-2,2'-disulfonic acid (SITS), an inhibitor of anion exchange. The intracellular anion concentrations were determined from 31P or 19F nuclear magnetic resonance spectra from the erythrocyte suspensions. The influx rates for the titratable phosphate analogs exhibited bimodal pH dependence, reaching maximal levels at pH values that increased with increasing anion pK. This pH-dependent behavior is consistent with a transport channel that contains a titratable regulatory site which interacts with the translocated anion. Based upon the Henderson-Hasselbalch equation, the probability that a titratable anion will have an electric charge of equal magnitude to that of the titratable carrier is highest at a pH value exactly midway between the pK of the regulatory site and that of the anion. The pH maxima observed for the phosphate analogs indicate a pK for this site of 5.5 at 37 degrees C. Intracellular pH changes associated with influx indicated that transport of the "fast" anion phosphite is largely in monoionized form. Intracellular pH changes associated with transport of slow anions were predominantly determined by partial ionic equilibrium effects and did not indicate the ionization state of the transported anion. PMID- 3335538 TI - Late sigma factor of bacteriophage T4. Formation and properties of RNA polymerase promoter complexes. AB - Bacteriophage T4 late gene promoters do not display sequence homology in the -35 region (Christensen, A. C., and Young, E. T. (1982) Nature 299, 369-371), suggesting an unusual geometry of RNA polymerase-promoter interaction. We have analyzed in vitro utilization of a late T4 promoter by RNA polymerase reconstituted from E. coli core enzyme (E) and bacteriophage T4 late sigma factor (sigma gp55). The E sigma gp55 holoenzyme forms a stable promoter complex which lacks protein-DNA contacts upstream from position -30 and is sensitive to direct attack by heparin. This complex is capable of reiterative oligonucleotide synthesis (abortive initiation). Kinetic analysis of complex formation reveals a rapidly forming inactive intermediate (closed complex) which is slowly isomerized into a catalytically active form (open complex). The results indicate that all components essential for promoter binding, open complex formation, and initiation of transcription are present in the "downstream" part of the RNA polymerase molecule, which is defined by the -30 to +20 footprint. On the basis of these observations and the results of others, we suggest that during transcription initiation at bipartite (Escherichia coli) promoters, an "upstream" DNA-binding domain of RNA polymerase which recognizes specific sequence elements in the -35 region plays an auxiliary role by regulating the rate of productive interactions in the downstream part of the molecule through an allosteric mechanism. PMID- 3335539 TI - Studies on compound I formation of the lignin peroxidase from Phanerochaete chrysosporium. AB - Ligninase, isolated from the wood-destroying fungus Phanerochaete chrysosporium, catalyzes the oxidation of lignin and lignin-related compounds. Ligninase reacts with H2O2 to form the classical peroxidase intermediates Compounds I and II. We have determined the activation energy of ligninase Compound I formation to be 5.9 kcal/mol. The effect of pH and ionic strength on the rate of ligninase Compound I formation was studied. In contrast to all other peroxidases, no pH effect was observed. This is despite homology of active-site amino acids residues (Tien, M., and Tu, C.-P. D. (1987) Nature 326, 520-523) which are proposed to affect the pH profile of Compound I formation. Ligninase Compound I formation can also be supported by organic peroxides. The second-order rate constants with the organic peroxides are lower, suggesting that H2O2 is the preferred substrate. PMID- 3335540 TI - Identification of the cysteine residue in the active site of horse liver mitochondrial aldehyde dehydrogenase. AB - Aldehyde dehydrogenase catalyzes the oxidation of aldehydes to acids through the formation of a covalent intermediate. It has been postulated that a cysteine residue could be acting as the active site nucleophilic group. Although N ethylmaleimide was found to react with many cysteines it was possible by doing the reaction in the presence of chloral hydrate, a substrate analog which functions as a competitive inhibitor, to label cysteine at position 49 in the horse liver mitochondrial enzyme. The dehydrogenase activity was lost as the residue was modified, consistent with the possibility that the residue was an integral component of the active site of the enzyme. Cysteines at positions 162 and 369 also could be modified. It is suggested that cysteine 162 may function as part of a site capable of hydrolyzing nitrophenyl acetate. Details of the second site will appear in the accompanying paper (Tu, G. C., and Weiner, H. (1988) J. Biol. Chem. 263, 1218-1222). It appeared that the substrate-binding domain was in the N-terminal portion of the enzyme while the coenzyme binding domain was in the C-terminal portion. During this investigation 133 of the 500 residues of the horse liver enzyme were sequenced. These showed about 95% sequence identity with those of the human enzyme. Inasmuch as both beef and rat liver enzymes also share 95% identity with the human enzyme it can be expected that the results found with the horse liver enzyme can be applicable to all mammalian aldehyde dehydrogenase. PMID- 3335541 TI - Evidence for two distinct active sites on aldehyde dehydrogenase. AB - Aldehyde dehydrogenase can catalyze the hydrolysis of esters such as p nitrophenyl acetate as well as oxidize aldehydes to acids. It has not been proven unequivocally that the two reactions occur at the same active site. In the accompanying paper (Tu, G. C., and Weiner, H. (1988) J. Biol. Chem. 263, 1212 1217) evidence was presented which showed that cysteine at position 49 was at the active site for the dehydrogenase reaction. Evidence also was presented which showed that cysteine located at position 162 was susceptible to modification by N ethylmaleimide. It was shown here that the two activities of the enzyme can be differently protected from inactivation by substrate analogs. Furthermore, aldehydes were found to be poor inhibitors against the esterase reaction while ester was a good inhibitor against the dehydrogenase reaction. In addition, it was possible to modify cysteine 49 with N-ethylmaleimide but not find inhibition of the esterase reactivity until cysteine 162 was modified. It appears that horse liver aldehyde dehydrogenase has two separate active sites per subunit. The data fit a model where ester can be hydrolyzed at both sites but that aldehyde oxidation occurred only at position 49. PMID- 3335542 TI - Effect of alkaline pH on the activity of rat liver phenylalanine hydroxylase. AB - The pH optimum of rat liver phenylalanine hydroxylase is dependent on the structure of the cofactor employed and on the state of activation of the enzyme. The tetrahydrobiopterin-dependent activity of native phenylalanine hydroxylase has a pH optimum of about 8.5. In contrast, the 6,7-dimethyltetrahydropterin dependent activity is highest at pH 7.0. Activation of phenylalanine hydroxylase either by preincubation with phenylalanine or by limited proteolysis results in a shift of the pH optimum of the tetrahydrobiopterin-dependent activity to pH 7.0. Activation of the enzyme has no effect on the optimal pH of the 6,7 dimethyltetrahydropterin-dependent activity. The different pH optimum of the tetrahydrobiopterin-dependent activity of native phenylalanine hydroxylase is due to a change in the properties of the enzyme when the pH is increased from pH 7 to 9.5. Phenylalanine hydroxylase at alkaline pH appears to be in an altered conformation that is very similar to that of the enzyme which has been activated by preincubation with phenylalanine as determined by changes in the intrinsic protein fluorescence spectrum of the enzyme. Furthermore, phenylalanine hydroxylase which has been preincubated at an alkaline pH in the absence of phenylalanine and subsequently assayed at pH 7.0 in the presence of phenylalanine shows an increase in tetrahydrobiopterin-dependent activity similar to that exhibited by the enzyme which has been activated by preincubation with phenylalanine at neutral pH. Activation of the enzyme also occurs when m-tyrosine or tryptophan replace phenylalanine in the assay mixture. The predominant cause of the increase in activity of the enzyme immediately following preincubation at alkaline pH appears to be the increase in the rate of activation by the amino acid substrate. However, in the absence of substrate activation, phenylalanine hydroxylase preincubated at alkaline pH displays an approximately 2-fold greater intrinsic activity than the native enzyme. PMID- 3335543 TI - Oxidant-mediated inhibition of ligand uptake by the macrophage mannose receptor. AB - We have investigated the effect of oxidants on ligand recognition and internalization by the macrophage mannose receptor. Rat bone marrow macrophages were treated with increasing concentrations of H2O2 for 30 min at 37 degrees C. Fifty percent inhibition of ligand uptake was observed at 250 microM, with only 10% of control uptake remaining following exposure to 1 mM H2O2 for 30 min. Electron micrographic analysis of macrophages following H2O2 treatment showed no morphological alterations compared to untreated cells. Ligand uptake was also inhibited by the following H2O2 generating systems: menadione, xanthine/xanthine oxidase, glucose/glucose oxidase, and phorbol 12-myristate 13-acetate-stimulated polymorphonuclear leukocytes. Inhibition could be blocked by catalase plus or minus superoxide dismutase. Treatment of macrophages at 4 degrees C with H2O2 had no effect on ligand binding, whereas treatment with H2O2 at 37 degrees C reduced binding to 15% of control levels and decreased the number of surface receptors to one-third of control cells. H2O2 treatment inhibited ligand degradation by macrophages, but did not prevent ligand movement from the surface to the interior of the cell. In addition, ligand delivery to lysosomes was blocked by oxidant treatment. These results suggest that treatment of macrophages with reagent H2O2 or H2O2-generating systems inhibits the normal ligand delivery and receptor recycling process involving the mannose receptor. Potential mechanisms might include receptor oxidation, alterations in ATP levels, or membrane lipid peroxidation. PMID- 3335545 TI - Interaction of bilirubin with the synaptosomal plasma membrane. AB - The interaction of the neurotoxic pigment bilirubin with synaptosomal plasma membrane vesicles (SPMV) isolated from rat brain was investigated. The interaction seems to involve three steps: (a) a rapid formation of an electrostatic complex between bilirubin and polar lipid head groups; (b) a slow inclusion of the pigment into the hydrophobic core of the membrane; and (c) a SPMV-induced bilirubin aggregation, observed when membrane capacity for bilirubin is exceeded. The association constant of the initial complex increased markedly when pH was lowered below 7.4, particularly in SPMV isolated from newborn rats. A preferential binding of bilirubin to pure gangliosides and sphingomyelin was observed, thus suggesting a role for these lipids as first targets of the pigment in the synaptic membrane. The inclusion of bilirubin into the membranes was gradually enhanced when decreasing the pH or the age of the rats from which SPMV were isolated. In addition, membranes from 2-day-old rats have a higher capacity for bilirubin incorporation compared to those from adult rats. Experiments with reconstituted liposomes of varying protein and cholesterol contents suggest that the effect of age may be related to changes in synaptosomal membrane fluidity during development. Our results support the hypothesis that the interaction of bilirubin with the synaptic membrane plays an important role in the molecular mechanisms of bilirubin neurotoxicity. PMID- 3335544 TI - A mammalian mutant cell lacking detectable lanosterol 14 alpha-methyl demethylase activity. AB - A Chinese hamster ovary cell mutant, AR45, was selected for amphotericin B resistance after treatment with the mutagen ethyl methanesulfonate. The mutant is a cholesterol auxotroph with a deficiency in cholesterol biosynthesis. Whole cell experiments demonstrate that the mutant accumulates the C30 sterols, lanosterol and dihydrolanosterol, under culture conditions which promote active sterol biosynthesis. Metabolic studies show that the C29 sterol demethylation product of lanosterol, but not lanosterol itself, is actively converted to end product cholesterol by whole cells as well as by microsomal preparations derived from the mutant. Detectable amounts of several cytochromes can be observed spectrally in the AR45 demonstrating that it is not a general heme-deficient mutant. Collectively, these results characterize the AR45 mutant cells as being lanosterol 14 alpha-methyl demethylase-deficient. The cell line should prove useful in studying regulation of the demethylase enzyme and the putative endogenous regulatory oxysterol. It should also be a useful tool in the molecular cloning and elucidation of genetic properties of the demethylase. PMID- 3335546 TI - Isopentenoid synthesis in isolated embryonic Drosophila cells. Farnesol catabolism and omega-oxidation. AB - Kc cells divert minimally 40% of their mevalonate carbon to n-fatty acids and unidentified compounds covalently linked to macromolecules (Havel, C., Rector, E. R., II, and Watson, J. A. (1986) J. Biol. Chem. 261, 10150-10156). Furthermore mevalonate carbon diversion appears to occur at the polyprenyl 1-pyrophosphate level. This report summarizes initial efforts to define the mevalonate carbon diversion pathway. We demonstrate that Kc cell extracts readily metabolize [14C]farnesyl 1-pyrophosphate and [14C]farnesol, via common intermediates, to identical 14C-products. Two of the major 14C-products were identified as trans,trans-3,7,11-trimethyl-2,6,10-dodecatrien-1,12-dioic acid and trans-3,7 dimethyl-2,6-decadien-1,10-dioic acid. Similar acids were also synthesized by supplemented rat liver extracts incubated with [14C]farnesol. We conclude that (a) mevalonate carbon diversion at the level of polyprenyl 1-pyrophosphate is a viable metabolic strategy, (b) polyprenols are oxidized to alpha,omega-prenyl dicarboxylic acids which are catabolized from the omega-terminus, and (c) this metabolic process is not limited to insect cells. PMID- 3335547 TI - Studies on Ca(II) binding to gamma-carboxyglutamic acid. Use of thermal decarboxylation to probe metal ion/gamma-carboxyglutamic acid interactions. AB - The thermal decarboxylation of N-benzyloxycarbonyl-L-gamma-carboxyglutamic acid alpha-methyl ester [Z)-L-Gla-OMe) has been studied. In the presence of increasing amounts of calcium or magnesium ions, lyophilized powders of (Z)-L-Gla-OMe exhibit a corresponding increase in thermal stability. Both magnesium and calcium form relatively tight, thermally stable complexes with (Z)-L-Gla-OMe at high metal ion concentrations. Differences between Ca(II) and Mg(II) binding are noted at low metal ion concentrations, where (Z)-L-Gla-OMe is in excess. Under these conditions, complex formation with Mg(II) apparently favors a 2:1 Gla-magnesium ion complex in which both Gla residues are unstable to thermal decarboxylation. Calcium ion complexes, however, are found to favor a 3:1 Gla-calcium ion complex in which 1 of the 3 Gla residues is thermally stable. PMID- 3335548 TI - Ca2+ binding effects on protein conformation and protein interactions of canine cardiac calsequestrin. AB - Calsequestrin is a Ca2+-binding protein located intraluminally in the junctional sarcoplasmic reticulum (SR) of striated muscle. In this study, Ca2+ binding to cardiac calsequestrin was assessed directly by equilibrium dialysis and correlated with effects on protein conformation and calsequestrin's ability to interact with other SR proteins. Cardiac calsequestrin bound 800-900 nmol of Ca2+/mg of protein (35-40 mol of Ca2+/mol of calsequestrin). Associated with Ca2+ binding to cardiac calsequestrin was a loss in protein hydrophobicity, as revealed with use of absorbance difference spectroscopy, fluorescence emission spectroscopy, and photoaffinity labeling with the hydrophobic probe 3 (trifluoromethyl)-3-(m-[125]iodophenyl)diazirine. Ca2+ binding to cardiac calsequestrin also caused a large change in its hydrodynamic character, almost doubling the sedimentation coefficient. We observed that cardiac calsequestrin was very resistant to several proteases after binding Ca2+, consistent with a global effect of Ca2+ on protein conformation. Moreover, Ca2+ binding to cardiac calsequestrin completely prevented its interaction with several calsequestrin binding proteins, which we identified in cardiac junctional SR vesicles for the first time. The principal calsequestrin-binding protein identified in junctional SR vesicles exhibited an apparent Mr of 26,000 in sodium dodecyl sulfate polyacrylamide gels. This 26-kDa calsequestrin-binding protein was greatly reduced in free SR vesicles and absent from sarcolemmal vesicles and was different from phospholamban, an SR regulatory protein exhibiting a similar molecular weight. Our results suggest that the specific interaction of calsequestrin with this 26-kDa protein may be regulated by Ca2+ concentration in intact cardiac muscle, when the Ca2+ concentration inside the junctional SR falls to submillimolar levels during coupling of excitation to contraction. PMID- 3335549 TI - Primary structure of human pepsinogen C gene. AB - The entire human pepsinogen C gene has been isolated from a cosmid genomic library. The nucleotide sequences of all the exons and the 5'- and 3'-flanking regions of the gene are presented. The organization of the gene is fundamentally compatible with those of other aspartic proteinases, allowing us to conclude that the genes of these aspartic proteinases including pepsinogen C are derived from a common ancestral gene. The predicted 388-residue amino acid sequence of human pepsinogen C consists of a signal sequence of 16-amino acid residues, an activation peptide of 43 residues, and the mature pepsin of 329 residues containing the two active-site aspartic acids. In the light of present notions about eukaryotic gene expression, possible regulatory roles of the oligonucleotide DNA sequences in the promoter region of the gene are discussed. PMID- 3335550 TI - Enhanced carboxyl methylation of membrane-associated hemoglobin in human erythrocytes. AB - The alpha- and beta-chains of hemoglobin (Hb) are methylated in intact erythrocytes and in cellular extracts by a protein D-aspartate methyltransferase (EC 2.1.1.77) specific for D-aspartyl and L-isoaspartyl residues. During an 18-h incubation of intact erythrocytes with L-[methyl-3H]methionine, the subfraction of Hb molecules associated with the membrane becomes progressively enriched with methyl esters, reaching a specific activity 10-fold that of cytosolic Hb. The enhanced methylation of membrane Hb in intact cells appears not to result from its methylation at sites with inherently greater stability, since salt-extracted membrane Hb 3H-methyl esters and cytosolic Hb 3H-methyl esters are hydrolyzed at similar rates at pH 8.4 in vitro. Oxidative treatment of column-purified Hb with acetylphenylhydrazine produces an immediate 4-fold increase in its specific methyl-accepting activity coincident with the production of hemichrome forms known to possess a higher affinity for membrane binding sites. Together, the results suggest that the methyltransferase preferentially recognizes partially denatured Hb molecules which possess a higher affinity for membrane binding sites, similar to Hb forms observed in senescent erythrocytes. PMID- 3335552 TI - The ionization and distribution behavior of oleic acid in chylomicrons and chylomicron-like emulsion particles and the influence of serum albumin. AB - A reproducible, fairly narrow-sized population of rat lymph chylomicrons, approximately 100 nm, was isolated by centrifugation and combined with low levels of [1-13C]oleic acid for NMR studies. The carboxyl chemical shift was monitored as a function of aqueous pH to characterize the ionization behavior of the fatty acid in these particles. The titration curves were very similar to those for oleic acid in equivalent-sized emulsion particles composed of egg phosphatidylcholine and triolein. A simple partition-ionization model was fitted to the data to derive values for apparent ionization constant, expressed as pKapp, of 7.4-7.5 and the "true" surface to core partition coefficient of approximately 7 for oleic acid in chylomicrons. The fatty acid in chylomicrons thus appeared to be largely associated with the surface regions of these particles. Addition of bovine serum albumin to the samples showed that near physiologic pH much of the fatty acid was bound to the albumin at fatty acid to albumin-binding stoichiometries as high as 5.1 and with mass ratios of greater than 2 in favor of the lipid or lipoprotein particles. Lowering the pH of the medium shifted the distribution of fatty acid away from albumin so that at pH 5 with the emulsion, virtually all the fatty acid was associated with the lipid. The behavior observed under physiologic conditions is consistent with the rapid clearance and redistribution of fatty acid generated in these particles by lipolytic processes. However, under conditions of severe acidosis, hyperlipidemia, and hypoalbuminemia a significant portion of fatty acids might be retained in triglyceride-rich lipoproteins and their remnants and affect subsequent metabolism. PMID- 3335551 TI - Synthesis and binding affinity of an iodinated juvenile hormone. AB - The synthesis of the first iodinated juvenile hormone (JH) in enantiomerically enriched form is reported. This chiral compound, 12-iodo-JH I, has an iodine atom replacing a methyl group of the natural insect juvenile hormone, JH I, which is important in regulating morphogenesis and reproduction in the Lepidoptera. The unlabeled compound shows approximately 10% of the relative binding affinity for the larval hemolymph JH binding protein (JHBP) of Manduca sexta, which specifically binds natural 3H-10R,11S-JH I (labeled at 58 Ci/mmol) with a KD of 8 X 10(-8) M. It is also approximately one-tenth as biologically active as JH I in the black Manduca and epidermal commitment assays. The 12-hydroxy and 12-oxo compounds are poor competitors and are also biologically inactive. The radioiodinated [125I]12-iodo-JH I can be prepared in low yield at greater than 2500 Ci/mmol by nucleophilic displacement using no-carrier-added 125I-labeled sodium iodide in acetone; however, synthesis using sodium iodide carrier to give the approximately 50 Ci/mmol radioiodinated ligand proceeds in higher radiochemical yield with fewer by-products and provides a radioligand which is more readily handled in binding assays. The KD of [125I]12-iodo-JH I was determined for hemolymph JHBP of three insects: M. sexta, 795 nM; Galleria mellonella, 47 nM; Locusta migratoria, 77 nM. The selectivity of 12-iodo-JH I for the 32-kDa JHBP of M. sexta was demonstrated by direct autoradiography of a native polyacrylamide gel electrophoresis gel of larval hemolymph incubated with the radioiodinated ligand. Thus, the in vitro and in vivo activity of 12-iodo-JH I indicate that it can serve as an important new gamma-emitting probe in the search for JH receptor proteins in target tissues. PMID- 3335553 TI - Rapid phosphorylation of microtubule-associated proteins through distinct mitogenic pathways. AB - Mitogenic stimulation of sparse quiescent Swiss 3T3 cells with serum induces a transient reorganization of microtubules which may be necessary for generation or transduction of the mitogenic signal(s). Recently, several studies have shown that microtubule-associated proteins (MAPs) modulate microtubule-mediated functions in vitro and in vivo. We have analyzed, by two-dimensional electrophoresis, the molecular changes in MAPs associated with microtubules in situ following cell activation. By as early as 15 min after addition of serum, several of the MAPs present in quiescent cells are lost from the assembled microtubule fraction while one additional MAP becomes evident. This new MAP is a phosphoprotein whose appearance is independent of protein synthesis. Four additional MAPs also become phosphorylated, and this phosphorylation is accompanied by a partial redistribution of MAPs into the unassembled soluble fraction. Stimulation of cells with purified platelet-derived growth factor or phorbol tumor promoter, a direct activator of protein kinase C, also induces phosphorylation of the same MAPs and DNA synthesis. These results demonstrate that activation of the protein kinase C pathway is sufficient to promote the phosphorylation of MAPs and mitogenesis. However, epidermal growth factor, which does not activate protein kinase C, also stimulates phosphorylation of MAPs and DNA replication. Furthermore, down-regulation of the protein kinase C pathway does not prevent these responses. We conclude that phosphorylation of MAPs and mitogenesis can proceed through protein kinase C-dependent and -independent pathways in 3T3 cells. PMID- 3335554 TI - Electron probe microanalysis of the subcellular compartments of bovine adrenal chromaffin cells. Comparison of chromaffin granules in situ and in vitro. AB - The elemental and water content of cultured bovine adrenal chromaffin cells and their secretory chromaffin granules have been measured and compared with isolated chromaffin granules using quick freezing, ultracryomicrotomy, and electron microprobe analysis methods. In units of millimole/kilogram dry weight (+/- S.E.) granules in situ contained: P, 523 +/- 32; K+, 124 +/- 9; S, 82 +/- 3; Cl-, 74 +/ 9; Ca2+, 13 +/- 2; Mg2+, 6 +/- 2; and Na+, -2 +/- 2. Following routine isolation in isotonic sucrose buffer, granule K and Cl- had decreased while granule Na+ increased. Cl- exhibited a consistent decrease to 35-40 mmol/kg dry weight. Granule Na+ and K+ concentrations ranged from 43 to 12 mmol/kg and 28 to 60 mmol/kg dry weight, respectively, depending on the Na+ and K+ content of the buffer. Despite the redistribution of monovalent ions, granule Ca2+, granule P, being in the form of ATP, and granule S, being in the form of protein, were not significantly changed. The stability of these elements is consistent with the existence of a stable storage complex for Ca2+, ATP, and protein. Using the granule as an internal standard with a water content of 66%, the water contents of external space, nucleus, cytoplasm, and mitochondria were estimated to be 89, 88, 82, and 70%, respectively. Wet weight concentrations for each element were calculated for granules and cytoplasm from which the transgranular concentration gradients for K+, Cl-, and Na+ were determined. Cl-, a permeant anion, was 2-fold higher in the granule than in the cytoplasm while K+, a slightly permeant cation, had an opposite distribution ratio slightly less than two. Together, the K+ and Cl- data suggest the presence of an inside-positive granule membrane potential of approximately 10-16 mV. The surprising lack of Na+ from the granule matrix suggests a hugh inward gradient for Na+ even though the Na+ content of chromaffin cell cytoplasm is low at 5 mmol/kg water. The lack of an outward Na+ gradient is important in that it indicates that the previously described electroneutral Na+ Ca2+ exchange system, by which isolated granules accumulate Ca2+, does not operate in mature granules in situ. Consequently, if chromaffin granules regulate internal calcium during stimulus secretion coupling, a mechanism other that Na+ Ca2+ exchange is necessary. PMID- 3335555 TI - Secretion of rabbit C-reactive protein by transfected human cell lines is more rapid than by cultured rabbit hepatocytes. AB - C-reactive protein (CRP) is a major acute phase protein in humans and rabbits. Its synthesis by the liver varies over a 1000-fold range depending on the presence and severity of inflammatory stimuli. In previous studies of synthesis and secretion of rabbit CRP, we showed that secretion becomes more efficient over the course of the acute phase response as CRP synthesis rates increase (Macintyre, S.S., Kushner, I., and Samols, D. (1985) J. Biol. Chem. 260, 4169 4173). The current studies were undertaken to help distinguish between two alternative explanations for this finding: 1) that secretion efficiency may simply be a property of the rate of synthesis and intracellular concentration of CRP or 2) that secretion may be regulated by separate intracellular mechanisms. A fusion gene containing the mouse metallothionein I promoter linked to the protein coding region of the rabbit CRP gene was introduced into the human hepatoma cell line, NPLC, and the nonliver cell line, HeLa. In this system a graded response of the mouse metallothionein I promoter following exposure to increasing zinc concentrations results in increasing CRP synthesis. Unlike hepatocytes from rabbits undergoing the acute phase response, we found that rabbit CRP was secreted by these transfected cell lines with a very high degree of efficiency which was independent of the rate of CRP synthesis. This finding implies that normal rabbit hepatocytes retard the secretion of CRP and that this inhibition is diminished as the acute phase response progresses. It further indicates that the relationship between changes in synthetic rate and efficiency of secretion of rabbit CRP is not a causal one and that synthesis and secretion of CRP by rabbit hepatocytes are regulated by independent intracellular mechanisms during the acute phase response. PMID- 3335556 TI - Subunit interactions of skeletal muscle myosin and myosin subfragment 1. Evidence for heavy chain-alkali light chain association-dissociation equilibrium. AB - Modification of the free alkali light chains of myosin by iodoacetylation results in a much lower extent of exchange into myosin subfragment 1 by the thermal hybridization procedure (Burke, M., and Sivaramakrishnan, M. (1981) Biochemistry 20, 5908-5913). As reported by others (Wagner, P. D., and Stone, D. B. (1983) J. Biol. Chem. 258, 8876-8882), free alkali light chains modified by iodoacetate at their single sulfhydryl residue exhibit minimal exchange into intact myosin. However, when unmodified alkali light chain is used to probe for exchange, close to the theoretical limit of exchange is observed for subfragment 1, and significant levels of exchange are found for myosin. It appears that modification of the free alkali light chain alters the structure of the protein, and this causes either a marked reduction in its affinity for the heavy chain or in its ability to enter the light chain binding site. This conclusion is supported by tryptic digestions done on the unmodified and modified free light chains where it is found that the latter is degraded at a much faster rate, indicating a more open structure for the modified protein. The observation that alkali light chain exchanges into myosin when unmodified alkali light chains are used indicates that the presence of the associated 5,5'-dithiobis-(2-nitrobenzoic acid) light chains does not preclude the reversible dissociation of this subunit from myosin under ionic and temperature conditions approaching the physiological state. PMID- 3335557 TI - Distal femoral varus osteotomy. AB - The results of twenty-three distal femoral varus osteotomies (in twenty-one patients) that were performed between 1977 and 1984 were evaluated. Fifteen osteotomies were done for osteoarthritis; three, for post-traumatic arthritis or deformity; three, for rheumatoid arthritis; and two, for renal osteodystrophy. The median age of the patients was fifty-six years (range, nineteen to seventy years). The length of follow-up averaged four years (range, two to nine years). The average tibiofemoral angle preoperatively was 18 degrees of valgus, which was corrected postoperatively to an average of 2 degrees of valgus. At follow-up, nineteen (83 per cent) of the twenty-three knees were rated as good or excellent according to The Hospital for Special Surgery knee score, which had improved from an average of 65 points preoperatively to 86 points post-operatively. Of the fifteen patients who had osteoarthritis (93 per cent), all but one had a good or excellent result. Most patients had no substantial improvement in the range of motion of the knee as a result of the operation. Eighty-six per cent of the patients expressed satisfaction with the outcome. We concluded that varus osteotomy of the distal part of the femur is a reliable and effective surgical procedure for the treatment of gonarthrosis associated with valgus deformity due to osteoarthritis or trauma. We do not recommend its use in patients who have rheumatoid arthritis or in those who have inadequate motion of the knee before the operation. PMID- 3335559 TI - Distal femoral varus osteotomy for valgus deformity of the knee. AB - Twenty-four patients who had degenerative arthritis of the lateral compartment of the knee that was associated with a valgus deformity and a superolateral tilt of the joint line were treated by distal femoral varus osteotomy. A surgical technique that was designed to produce a horizontal joint line and a tibiofemoral angle of zero degrees is described. At an average length of follow-up of four years, twenty-two of twenty-four patients had a successful result as judged by our protocol for evaluation. One osteotomy had to be revised for failure of fixation, and one patient had a pulmonary embolism that had a satisfactory outcome after the administration of anticoagulants. One patient required manipulation of the knee at six months. The simple surgical technique that we used was effective in realigning the femoral with the tibial axis in patients who had a valgus deformity of the knee, a superolateral tilt of the joint line, and osteoarthritis of the lateral compartment. PMID- 3335558 TI - Deep-vein thrombosis and continuous passive motion after total knee arthroplasty. AB - Seventy-five of 150 consecutive patients who underwent total knee arthroplasty had routine physiotherapy and seventy-five had continuous passive motion of the lower limb that had been operated on as well as routine physiotherapy. A pulmonary embolus did not develop in any patient, but about 40 per cent had thrombosis in the veins of the calf, whether passive motion had been administered or not. Radiographically, the deep-vein thrombosis was seen to extend into or proximal to the popliteal vessel in 5 per cent of the patients in each group. Sex, age, obesity, or a history of hypertension or diabetes did not influence the incidence of venous thrombosis, but there was a higher incidence in patients in whom cement was used for fixation of the total knee components, irrespective of the use of continuous passive motion of the limb. PMID- 3335560 TI - Effusions in the knee in elderly patients who were operated on for fracture of the hip. AB - The incidence of an effusion in the knee in 155 consecutive elderly patients who had been operated on for a proximal femoral fracture was studied. The preoperative incidence had been 7.7 per cent in the ipsilateral knee and 1.3 per cent in the contralateral knee. Postoperatively, fifty patients (32.3 per cent) had an effusion on the ipsilateral side. In seven of them, the effusion had been present before the operation. All of the effusions subsided completely within three weeks after the operation. Results of the laboratory analysis of a specimen of the effused material from eight patients who were chosen at random showed non inflammatory fluid. Probably the effusions were traumatic in origin, and it is likely that they were a response to stresses that had been incurred during the operation or at the time of fracture. PMID- 3335561 TI - Digital lipoma of the foot in a child. A case report. PMID- 3335562 TI - Traumatic dislocation of the hip caused by capsular interposition in a child. A case report. PMID- 3335563 TI - Concurrent fractures of the ipsilateral scaphoid and radial head. Report of four cases. PMID- 3335565 TI - The antiglide plate for distal fibular fixation. A biomechanical comparison with fixation with a lateral plate. PMID- 3335564 TI - Syndrome of inappropriate anti-diuretic hormone secretion complicating metrizamide myelography. A case report. PMID- 3335566 TI - Injury to the popliteal artery as a complication of arthroscopic surgery. A report of two cases. PMID- 3335567 TI - Operative treatment of intra-articular fractures of the dorsal aspect of the distal phalanx of digits. PMID- 3335569 TI - Results of treatment of severe carpal tunnel syndrome without internal neurolysis of the median nerve. PMID- 3335570 TI - The anatomy and functional axes of the femur. PMID- 3335568 TI - Arthroplasty of the ipsilateral shoulder and elbow in patients who have rheumatoid arthritis. PMID- 3335571 TI - Disorders of the sacro-iliac joint in children. AB - The cases of seventeen children whose ages ranged from two to eighteen years and who were treated for a disorder of a sacro-iliac joint between 1975 and 1983 were reviewed retrospectively. Thirteen children were acutely ill, with a temperature of more than 38 degrees Celsius, and four had chronic symptoms that had persisted for three weeks to one year. Pain in the hip, thigh, and buttock was the most common symptom. Of the thirteen acutely ill patients, eleven had septic arthritis of a sacro-iliac joint, while one who had ankylosing spondylitis and one who had juvenile rheumatoid arthritis had acutely painful arthritis of a sacro-iliac joint. Of the four patients who had chronic symptoms, two had septic arthritis of a sacro-iliac joint; one, ankylosing spondylitis with sacro-iliac involvement; and one, eosinophilic granuloma of the ilium. Thus, thirteen patients had septic arthritis of a sacro-iliac joint and four had some other disorder. For the seventeen children who had acute or chronic symptoms, at admission the white blood-cell count ranged from 3,500 to 26,200 per cubic millimeter (average, 11,100 per cubic millimeter) and the sedimentation rate, as determined by the Westergren technique, ranged from twenty-two to sixty-five millimeters per hour (average, fifty millimeters per hour). Twelve of the plain radiographs of the seventeen patients were negative. The initial bone scans of all seventeen patients were positive in eleven and negative in six. Of these six, five had septic arthritis and one, juvenile rheumatoid arthritis. A computed tomographic scan was performed in four patients and was positive in all of them: three had septic arthritis and one had ankylosing spondylitis. Organisms were cultured successfully from blood, from material aspirated from the sacro-iliac joint, or from stool of all thirteen patients who had sepsis. The thirteen infections responded well to appropriate antibiotics, which were administered intravenously to seven patients and first intravenously and then orally to six. PMID- 3335572 TI - The treatment of scoliosis in cerebral palsy by posterior spinal fusion with Luque-rod segmental instrumentation. AB - Thirty-three patients who had cerebral palsy and scoliosis underwent posterior spinal fusion with Luque-rod segmental instrumentation. The mean curve measured 65 degrees preoperatively and 30 degrees postoperatively. The mean loss of correction was 3 degrees after a mean length of follow-up of forty months. As of the time of writing, pseudarthrosis had not developed in any patient. No patient had a broken rod or an increased neurological deficit. There were no major pulmonary complications. The most common early postoperative complication was wound infection, which occurred in five patients, none of whom required removal of the hardware. We concluded that posterior spinal fusion with Luque-rod segmental instrumentation is an effective method of obtaining and maintaining correction of a spinal curve, with minimum complications, in patients who have cerebral palsy and progressive scoliosis. PMID- 3335573 TI - Telemetric force measurements across the hip after total arthroplasty. AB - A telemeterized total hip prosthesis was implanted in one patient and force-data were obtained. Thirty-one days postoperatively, the magnitude of the joint contact force during double-limb stance was 1.0 times body weight. During ipsilateral single-limb stance the joint-contact force was 2.1 times body weight, and during the stance phase of gait the peak force typically was 2.6 to 2.8 times body weight, with the resultant force located on the anterosuperior portion of the ball. During stair-climbing, the force was 2.6 times body weight. At peak loads, the angle between the resultant force and the axis of the neck was 30 to 35 degrees and that between the resultant force and the plane of the prosthesis was 20 degrees. During stair-climbing or straight-leg raising, the out-of-plane orientation of the resultant force increased substantially. These data provide information concerning the forces that must be sustained by prosthetic hip joints during a number of common activities of daily living within the first month after implantation. The results also provide insight into the progression of early recovery and demonstrate the variety of forces that are generated during this period. PMID- 3335574 TI - Induction and characterization of an interface tissue by implantation of methylmethacrylate cement into the posterior part of the cervical spine of the dog. AB - After the implantation of methylmethacrylate cement into the posterior part of the cervical spine of the dog, a thick layer of connective tissue forms at the bone-cement interface. The tissue is six to eight millimeters thick and in all animals it surrounds the dorsal and lateral aspects of the masses of implanted cement, grows between the undersurface of the cement and the bone of the posterior elements, and completely covers that bone. This tissue was examined by light and electron microscopy and its collagenous components were extracted and analyzed biochemically by gel electrophoresis. Specific extracellular matrix proteins in the tissue at the bone-cement interface were also localized by immunohistochemistry. The tissue at the host-cement interface contained zones of fibrocytes and plump and teardrop-shaped cells within a collagenous matrix. Type I, Type-III, and Type-V collagen were extracted and were identified by gel electrophoresis. Type-V collagen and fibronectin were localized predominantly around the plump and teardrop-shaped cells. Type-IV collagen and laminin were localized predominantly in an area just beneath the teardrop-shaped cells at the surface of the tissue overlying the cement, suggesting that a basement-membrane like tissue had formed in this area. PMID- 3335575 TI - Dedifferentiated chondrosarcoma. AB - The cases of forty-six patients who had dedifferentiated chondrosarcoma were reviewed. Two groups were identified: one in which a low-grade malignant chondrosarcoma was the precursor lesion and one in which a moderate to high-grade malignant chondrosarcoma was the precursor lesion. The radiographic features of these lesions ranged from that of a cartilaginous lesion that appeared to be benign to that of a destructive osteolytic tumor in which the cartilaginous component was overshadowed by the dedifferentiated component. Only three of the forty-six patients survived for more than two years. Resection alone, even when it was wide or radical, was not successful in controlling this lethal sarcoma. PMID- 3335576 TI - Total knee arthroplasty in young adults who have rheumatoid arthritis. AB - At the Mayo Clinic, between 1978 and 1982, forty-four total knee arthroplasties were performed with cement in twenty-six adults who had rheumatoid arthritis. The age at operation ranged from nineteen to thirty-nine years old. The twenty-six patients were followed for two to eight years (average, five years). At the time of final follow-up, thirty-nine knees were free of pain and five were mildly painful during weight-bearing. The Hospital for Special Surgery knee score improved from a mean of 52 points preoperatively to 84 points postoperatively. There were twenty-four excellent, fourteen good, six fair, and no poor results. Radiographic analysis revealed an incomplete radiolucent line that was more than one millimeter in width adjacent to five tibial and four femoral components in eight knees (18 per cent). The positions of the components had not changed. Postoperatively, there was one transient peroneal palsy and two knees required patellar resurfacing. No revisions were performed for loosening of a prosthesis. We concluded that use of a cemented total knee prosthesis in a patient who has rheumatoid arthritis and is less than forty years old provides a satisfactory result and that the component will not loosen after an average of five years. PMID- 3335577 TI - Limits of movement in the human knee. Effect of sectioning the posterior cruciate ligament and posterolateral structures. AB - We applied specific forces and moments to the knees of fifteen whole lower limbs of cadavera and measured, with a six degrees-of-freedom electrogoniometer, the position of the tibia at which the ligaments and the geometry of the joint limited motion. The limits were determined for anterior and posterior tibial translation, internal and external rotation, and varus and valgus angulation from zero to 90 degrees of flexion. The limits were measured in the intact knee and then the changes that occurred with removal of the posterior cruciate ligament, the lateral collateral ligament, the popliteus tendon at its femoral attachment, and the arcuate complex were measured. The cutting order was varied, allowing us to determine the changes in the limits that occurred when each structure was cut alone and the amount of motion of the joint that was required for each structure to become taut and to limit additional motion when the other supporting structures had been removed. Removal of only the posterior cruciate ligament increased the limit for posterior tibial translation, with no change in the limits for tibial rotation or varus and valgus angulation. The additional posterior translation was least at full extension and increased progressively, reaching 11.4 millimeters at 90 degrees of flexion. The progressive increase in posterior translation with flexion was apparently due to slackening of the posterior portion of the capsule, as the translation nearly doubled when the posterolateral structures subsequently were removed. Removal of only the posterolateral extra-articular restraints increased the amount of external rotation and varus angulation. The average increase in external rotation depended on the angle of flexion; it was greatest at 30 degrees of flexion and decreased with additional flexion. At 90 degrees of flexion, the intact posterior cruciate ligament limited the increase in external rotation to only 5.3 degrees, less than one-half of the 13.0-degree increase that occurred at 30 degrees of flexion. Subsequent removal of the posterior cruciate ligament markedly increased external rotation at 90 degrees of flexion, resulting in a total increase of 20.9 degrees. The limit for varus angulation was normal as long as the lateral collateral ligament was intact. When the lateral collateral ligament was cut, the limit increased 4.5 degrees (approximately 4.5 millimeters of additional joint opening) when the knee was partially flexed (to 15 degrees).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3335578 TI - Study of pressure of the normal anterior tibial compartment in different age groups using the slit-catheter method. AB - Using the slit-catheter method, the pressure of the anterior tibial compartment was studied in thirty volunteers, whose ages ranged from seventeen to eighty-five years, at rest and during and after exercise. The average resting pressure was +5.1 millimeters of mercury. There was a wide variation between subjects, although 95 per cent of them had a resting pressure of less than twelve millimeters of mercury. This pressure was not consistently or significantly affected by age. The pressure increased with exercise, but in an average of 3.4 minutes after the exercise was stopped it returned to within one millimeter of mercury of the resting pressure. The resting pressure was also found to be affected by the positions of the lower extremity and the trunk during measurement. To reduce this effect, it is recommended that for measurement of pressure in the lower extremity the patient should be lying supine and the big toe should be pointing vertically upward. PMID- 3335579 TI - Effect of osmolar and ionic composition of the extracellular fluid on transferrin endocytosis and exocytosis and iron uptake by reticulocytes. AB - The effects of osmolar and ionic factors on endocytosis and exocytosis were investigated using rabbit reticulocytes and 125I-59Fe labelled transferrin. Endocytosis and exocytosis of transferrin and the uptake of iron were inhibited by increasing the osmolality or decreasing the ionic strength or pH of the cell incubation medium. However, elevation of the pH above 8.0 inhibited endocytosis but not exocytosis. Replacement of the NaCl in the incubation medium by Nal, NaF, NaSCN, NaClO4, Na2SO4, Na phosphate, or Na Hepes inhibited endocytosis and iron uptake but only Nal, NaF, and NaSCN inhibited exocytosis. Transferrin exocytosis was insensitive to inhibitors of anion or cation transport, but endocytosis and iron uptake were inhibited by several anion transport inhibitors. Overall, transferrin endocytosis was more sensitive than exocytosis to most of the factors which were investigated, and the effects on the rates of endocytosis and iron uptake were quantitatively very similar. The results provide strong support for the concept that transferrin endocytosis is a necessary step in iron uptake by reticulocytes. They do not support the chemiosmotic models of exocytosis in their present formulations, but do not rule out the possible role of an osmotic event in exocytosis. PMID- 3335580 TI - Plasma membrane fluidity measurements in intact endothelial cells: effect of hyperoxia on fluorescence anisotropies of 1-[4-(trimethylamino)phenyl]-6-phenyl hexa-1,3,5-triene. AB - Fluorescence anisotropy measurements are widely used as sensitive indicators of cell membrane fluidity. 1-[4-(trimethylamino)phenyl]-6-phenyl hexa-1,3,5-triene (TMA-DPH) is a cationic fluorescent aromatic hydrocarbon that anchors at the lipid-water interface of membrane lipid bilayers. Its uptake into porcine pulmonary artery and aortic endothelial cells was monitored and the probe remained specifically localized on the cell surface for at least 4 h. It can therefore be recommended for use for specific plasma membrane lipid fluidity measurements in these cells. The effect of hyperoxia on plasma membrane fluidity was measured by using TMA-DPH. In both cell types, hyperoxic damage resulted in decreases in plasma membrane fluidity. Recovery was achieved 48 h after a 42-h hyperoxic exposure. These results indicate that TMA-DPH is a sensitive probe of plasma membrane lipid domains of pulmonary artery and aortic endothelial cells and that hyperoxia causes reversible changes in the physical state of superficial lipid domains of the plasma membrane of these cells. PMID- 3335581 TI - Stimulation of mono (ADP-ribosyl)ation by reduced extracellular calcium levels in human fibroblasts. AB - Lowering extracellular calcium in cultures of human diploid fibroblast-like cells caused a rapid depletion of NAD pools. This loss of NAD was reversed by restoring extracellular Ca2+ and was inhibited by 3-aminobenzamide, an inhibitor of ADP ribosyl transfer reactions. The concentrations of 3-aminobenzamide needed to inhibit the loss of NAD were consistent with those required to inhibit cellular mono(ADP-ribosyl) rather than poly(ADP-ribosyl) reactions. Calcium depletion did not inhibit the biosynthesis of NAD. These results suggest that mono(ADP ribosyl)ation is involved in the regulation of cellular Ca2+ levels. PMID- 3335583 TI - The learning disabled child: another frontier for nursing. PMID- 3335582 TI - Synergistic antiproliferative effects of glucocorticoids and interferon-alpha on some lymphoid cell lines. AB - The Daudi B lymphoblastoid cell line was previously demonstrated to be highly sensitive to the antiproliferative effect of recombinant interferon-alpha A (rIFN alpha A). In the present study, glucocorticoid hormones were shown to act synergistically with rIFN-alpha A to further increase the sensitivity of Daudi cells to rIFN-alpha A. At 10(-6) M, dexamethasone, prednisolone, or hydrocortisone alone had little effect on Daudi cell growth, but they greatly potentiated the antiproliferative activity of rIFN-alpha A. The synergy between rIFN-alpha A and glucocorticoids on Daudi cells was not related to the inhibitory effects of glucocorticoids on prostaglandin or leukotriene synthesis, since no synergy was observed between rIFN-alpha A and indomethacin or nordihydroguaiaretic acid. Glucocorticoids and rIFN-alpha A also had appreciable synergistic antiproliferative effects on two out of five other IFN-sensitive lymphoid cell lines. When Raji B lymphoblastoid cells, which were quite resistant to the antiproliferative effect of rIFN-alpha A, were treated with the combination of glucocorticoids and rIFN-alpha A, no significant synergistic effects were observed. The synergistic antiproliferative effects of glucocorticoids and rIFN-alpha A observed with some IFN-sensitive lymphoid cell lines in this in vitro study may have clinical relevance in the treatment of certain lymphoid malignancies that are sensitive to rIFN-alpha A therapy. PMID- 3335584 TI - Death in the classroom: a lesson in life. PMID- 3335585 TI - Nursing involvement in treatment decisions regarding newborns with congenital anomalies. PMID- 3335586 TI - Community care: pediatric home mechanical ventilation. PMID- 3335587 TI - Systematic monitoring: realities in practice. PMID- 3335588 TI - Development and implementation of unit-based monitors. PMID- 3335589 TI - Implementing a continuous unit-specific quality assurance monitor. PMID- 3335590 TI - Nursing peer review: monitoring the appropriateness and outcome of nursing care. PMID- 3335592 TI - State hospital: nursing quality assurance monitoring nursing practice. PMID- 3335591 TI - Using monitoring in a home care quality assurance program. PMID- 3335593 TI - Practical tools for quality assurance: criteria development sheet and data retrieval form. PMID- 3335594 TI - Interpretation: a critical component of the quality assurance process. PMID- 3335595 TI - Systematic monitoring: review of nursing care in a radiology department. PMID- 3335596 TI - Primary versus functional medication administration: monitoring and evaluating medication error rates. PMID- 3335597 TI - Development and implementation of systematic monitoring of medication errors. PMID- 3335598 TI - What to do when corrective actions is unsuccessful in reversing ongoing problems in nursing care. PMID- 3335599 TI - Systematic monitoring of generic standards of patient care. PMID- 3335600 TI - Effect of prolonged bedrest on the propensity for renal stone formation. AB - The effect of prolonged bedrest immobilization on urinary risk factors for stone formation and on the propensity for the crystallization of calcium salts was examined in eight normal subjects. During 5 weeks of bedrest, the mean urinary calcium excretion rose during the first week and remained elevated (from 5.68 to approximately 7.50 mmol/day). Mean urinary phosphorus excretion increased by the second week of bedrest and remained elevated (from 2.70 to approximately 30.6 mmol/day). Urinary sodium and uric acid excretion rose slightly, as did urinary magnesium. Urinary pH, oxalate, and citrate changed slightly or not at all. Owing to these biochemical alterations, urinary saturation of calcium phosphate, calcium oxalate, and monosodium urate increased significantly during bedrest, but that of uric acid did not change. The inhibitor activity against the spontaneous nucleation of brushite (CaHPO4.2H2O) and calcium oxalate was not altered significantly by bedrest. Thus, the propensity for the crystallization of stone forming calcium salts was enhanced by bedrest, suggesting that immobilization may confer increased risk for the formation of calcium-containing renal stones. PMID- 3335601 TI - Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant Graves' disease. AB - Some patients with hyperthyroid Graves' disease have increased serum T3 and normal or even low serum T4 levels during treatment with antithyroid drugs. These patients with elevated serum T3 to T4 ratios rarely have a remission of their hyperthyroidism. The aim of this study was to investigate thyroid iodine metabolism in such patients, whom we termed T3-predominant Graves' disease. Mean thyroid radioactive iodine uptake was 51.0 +/- 18.1% ( +/- SD) at 3 h, and it decreased to 38.9 +/- 20.1% at 24 h in 31 patients with T3-predominant Graves' disease during treatment. It was 20.0 +/- 11.4% at 3 h and increased to 31.9 +/- 16.0% at 24 h in 17 other patients with hyperthyroid Graves' disease who had normal serum T3 and T4 levels and a normal serum T3 to T4 ratio during treatment (control Graves' disease). The activity of serum TSH receptor antibodies was significantly higher in the patients with T3-predominant Graves' disease than in control Graves' disease patients (60.5 +/- 19.2% vs. 20.4 +/- 18.2%; P less than 0.001). From in vitro studies of thyroid tissue obtained at surgery, both thyroglobulin content and iodine content in thyroglobulin were significantly lower in patients with T3-predominant Graves' disease than in the control Graves' disease patients. Thyroid peroxidase (TPO) activity determined by a guaiacol assay was 0.411 +/- 0.212 g.u./mg protein in the T3-predominant Graves' disease patients, significantly higher than that in the control Graves' disease patients (0.129 +/- 0.112 g.u./mg protein; P less than 0.01). Serum TPO autoantibody levels determined by immunoprecipitation also were greater in T3-predominant Graves' disease patients than in control Graves' disease patients (52.6 +/- 27.7% vs. 32.4 +/- 11.4%; P less than 0.05). Binding of this antibody to TPO slightly inhibited the enzyme activity of TPO, but this effect of the antibody was similar in the two groups of patients. The data suggest enhanced iodine metabolism in the thyroid gland of patients with T3-predominant Graves' disease, which may relate to the discordant T3 overproduction in patients with this type of Graves' disease. PMID- 3335602 TI - Human serum alpha 2HS-glycoprotein modulates in vitro bone resorption. AB - We previously isolated a family of bone-resorbing proteins from human cancer ascites fluid and established that the three purified bone-resorbing proteins were chemically and immunochemically related to each other and to alpha-2HS glycoprotein (alpha 2HS). After this finding we purified the normal human serum counterpart of these ascites proteins and studied its effects on bone resorption. The bone-resorbing properties of normal human serum alpha 2HS were examined in vitro over a wide dose range. This normal human serum glycoprotein had a biphasic effect on 45Ca2+ release from bone. More specifically, this protein stimulated bone resorption at the lower concentrations tested, with a maximum effect [treated over control ratio of 2.5 +/- 0.30 (+/- SE); P less than 0.01] at 40 micrograms/mL. In contrast, at doses above 40 micrograms/mL, a sharp decline in calcium mobilization occurred, with a return to baseline occurring above 80 micrograms/mL. These results suggest that serum alpha 2HS may participate in the regulation of bone metabolism in vivo. PMID- 3335603 TI - Intrathyroidal dendritic cells. AB - The presence, marker pattern, and ultrastructure of antigen-presenting dendritic cells were studied in normal thyroid glands from 9 subjects (6 obtained at surgery; 3 at autopsy) and in the thyroid glands form 13 patients with Graves' hyperthyroidism, 10 patients with simple nontoxic goiter, and 1 patient with Hashimoto's disease (all obtained at surgery). The immunohistochemical characterization of the cells was carried out using the monoclonal antibodies OKIa (class II MHC determinants), RFD1 and L25. These latter monoclonal antibodies react strongly with active dendritic cells in T-cell areas of secondary lymphoid organs (the interdigitating cells in lymph nodes and spleen). Antigen-presenting dendritic cells were defined as cells with an eccentric reniform nucleus, long cytoplasmic protrusions, and strong membrane-bound class II MHC positivity combined with little or no cytoplasmic acid phosphatase activity. According to these criteria normal human thyroid tissue contained a few dendritic cells; they were localized outside the thyroid follicles. These dendritic cells in normal thyroid tissue lacked the marker molecules identified by the monoclonal antibodies RFD1 and L25. In fact, the majority of the dendritic cells were strongly positive for the C3bi receptor (identified by the monoclonal antibody FK 24), which indicates a more monocyte/macrophage character of the cell. In Hashimoto's goiter, Graves' disease, and sporadic nontoxic goiter (which we consider an autoimmune thyroid disease) the numbers of dendritic cells were higher compared to those in the normal gland, and these dendritic cells were clearly positive for RFD1 and L25. The cells were often seen in contact with a few intrathyroidal lymphocytes, forming small lymphoid cell clusters. They were also found in the T-cell zones of larger well organized intrathyroidal lymphoid structures (focal thyroiditis). On ultrastructural examination the dendritic cells in Graves' glands, Hashimoto's goiter, and sporadic nontoxic goiter were similar to the interdigitating cells present in secondary lymphoid organs. The data suggest active involvement of dendritic cells in the immune process in the thyroids of patients with autoimmune thyroid disease. PMID- 3335604 TI - Side-effects of spironolactone therapy in the hirsute woman. AB - Spironolactone, an aldosterone antagonist with antiandrogenic activities, is often used to treat hirsute women. Several investigators have reported beneficial effects of such treatment, but the dosages used and side-effects encountered differ in their reports. To clarify this issue, 26 consecutive premenopausal women with idiopathic hirsutism were prospectively evaluated during spironolactone treatment. Sixteen women initially received 100 mg spironolactone twice daily on days 4-21 of their menstrual cycles. In 11 women (68%), the dosage had to be decreased or the medication discontinued due to side-effects. The major side-effect, metrorrhagia with 14-day cycles, occurred in 9 women (56%). This side-effect, while not dangerous, was intolerable to these women. In one woman, spironolactone was discontinued because of urticaria and in another because of scalp hair loss. Ten women initially received 50 mg spironolactone twice daily on days 4-21 of their menstrual cycles. Two developed metrorrhagia, but no other side-effects were noted. Because of the incidence of metrorrhagia at higher dosages, we recommend that spironolactone be administered cyclically at a starting dosage of 50 mg twice daily on days 4-21 of the menstrual cycle. Alternatively, one may consider adding cyclical estrogen/progesterone therapy to continuous spironolactone therapy. PMID- 3335605 TI - Androstanediol glucuronide isomers in normal men and women and in men infused with labeled dihydrotestosterone. AB - 3 alpha-Androstanediol glucuronide (Adiol G) is a major metabolite of dihydrotestosterone (DHT). Adiol G actually represents 2 different compounds, since the glucuronide can be conjugated at the 3-carbon position (Adiol 3-G) or at the 17-carbon position (Adiol 17-G). To determine which glucuronide represents the predominant physiological DHT metabolite and which isomer is the major circulating form, we developed a RIA to directly measure Adiol 3-G in serum extracts. In 10 normal men, mean serum Adiol 3-G and total Adiol G levels were 4.44 +/- 0.49 (+/- SE) nmol/L (208 +/- 23 ng/dL) and 27.9 +/- 2.8 nmol/L (1310 +/ 129 ng/dL), respectively (13.9 +/- 3.0% of Adiol G was Adiol 3-G). In 10 normal women sampled during the early follicular phase, mean serum Adiol 3-G and total Adiol G levels were 2.64 +/- 0.64 nmol/L (124 +/- 30 ng/dL) and 14.9 +/- 1.5 nmol/L (697 +/- 69 ng/dL), respectively (17.4 +/- 3.6% of Adiol G was Adiol 3-G). In 4 normal men infused for 8 h with tritiated DHT, 17.4 +/- 3.4% of the resulting tritiated Adiol G was Adiol 3-G. These results indicate that Adiol 17-G is the predominant circulating form of Adiol G in normal men and women and that it is also the major Adiol G isomer derived from DHT. PMID- 3335606 TI - Impairment of prednisolone disposition in patients with Graves' disease taking methimazole. AB - This study was undertaken to determine the effect of methimazole on the pharmacokinetics of iv prednisolone in patients with Graves' disease. Twenty women were studied, including eight with severe infiltrative ophthalmopathy who had taken methimazole and T4 for at least 4 months, six with severe infiltrative ophthalmopathy who had undergone subtotal thyroidectomy and, therefore, required no antithyroid treatment, and six age-matched normal women. All were euthyroid. Each women received 0.54 mg/kg prednisolone as an iv bolus dose. Plasma total and unbound prednisolone concentrations were measured at multiple times during a 10-h study period by high pressure liquid chromatography and equilibrium dialysis. The clearance of both total and unbound prednisolone was increased significantly in the women receiving methimazole therapy compared to values in both control groups. The volume of distribution at steady state was similar in all groups. These results suggest that patients receiving methimazole have enhanced prednisolone metabolism and, therefore, they may require higher prednisolone doses. PMID- 3335607 TI - High serum progesterone in hyperthyroid men with Graves' disease. AB - We measured serum progesterone in five men with hyperthyroidism due to Graves' disease. All had elevated serum progesterone levels before treatment with an antithyroid drug, and their serum progesterone levels declined concomitantly with their serum thyroid levels during treatment. Progesterone enhances estrogen's stimulation of mammary gland growth, and our findings suggest that progesterone may play a role in the gynecomastia that occurs in men with hyperthyroidism. PMID- 3335608 TI - Amplification of nocturnal melatonin secretion in women with functional hypothalamic amenorrhea. AB - Plasma melatonin levels were determined by a sensitive RIA at 30 min intervals for 24h in 7 women with functional hypothalamic amenorrhea (HA) and in 7 age and season matched normal cycling women in the early follicular phase (NC). While daytime melatonin concentrations were nondetectable in both groups, the integrated nocturnal levels were 3-fold greater in HA (244 +/- 58 (SE) vs 74 +/- 32 pmol-min/Lx10(3), p less than 0.005). This melatonin increase in HA was due to an elevated peak amplitude (p less than 0.01) and extended duration (p less than 0.05). The latter was mostly due to a significant delay in the offset time of the amplified nocturnal melatonin secretion. PMID- 3335609 TI - Lipoproteins, lipolytic enzymes, and hormonal status in hypothyroid women at different levels of substitution. AB - Serum lipoproteins and postheparin plasma lipoprotein lipase and hepatic lipase (HL) activities were determined in 23 hypothyroid women treated with graded doses of thyroxine (T4) (50, 100, and 150 micrograms/day), each given for 3 weeks. Since the sex hormone-binding globulin (SHBG) and thereby serum sex steroid concentrations are sensitive to thyroid status, we also measured serum testosterone, estradiol, and SHBG at each time. Stepwise T4 treatment resulted in gradual improvement in thyroid status. Concomitantly, serum low density lipoprotein (LDL) cholesterol decreased in a linear fashion from a mean of 4.72 +/- 0.31 (+/- SEM) to 3.21 +/- 0.18 mmol/L (P less than 0.001) after the largest dose. In contrast, serum high density lipoprotein (HDL) cholesterol decreased, although not in a dose-dependent fashion, from 1.61 +/- 0.07 to 1.44 +/- 0.05 mmol/L (P less than 0.001) after the largest dose. Serum SHBG increased along with improvement of thyroid function, but this increase did not have major impact on the changes in LDL during T4 treatment, as judged by multiple regression analysis. Thus, serum LDL correlated independently only with T4 (r = -0.38; P less than 0.001). The serum HDL changes were almost exclusively due to those in the HDL2 subfraction, and these were related to HL activity, which increased from 13.4 +/- 1.76 to 18.9 +/- 2.08 U/L after the largest dose. We conclude that thyroid hormones regulated serum HDL (HDL2) cholesterol mainly through their effect on HL. PMID- 3335610 TI - Variable estimates of serum growth hormone concentrations by different radioassay systems. AB - Many different assays are being used to measure serum GH concentrations in children with disorders of growth. We assessed four readily available methods to determine the comparability of the immunopotency estimates: standard double antibody RIA with pituitary standards from the National Hormone and Pituitary Program (assay 1) and from a commercial source (assay 2), a double antibody RIA with serum standards (assay 4), and a commercial immunoradiometric assay (assay 3). There was a high degree of relative correlation between assays (r = 0.95 0.98), but absolute potency estimates differed. Assays 1 and 2 were almost identical. Assay 3 yielded serum GH levels about 65% those of assay 1 or 2 and 80% those of assay 4. Assay 4 gave intermediate values between the low readings in assay 3 and higher values in assay 1 and 2. We conclude that substantial variation occurs in potency estimates in different GH assays. Such differences can affect the interpretation of many GH provocative and sampling studies. PMID- 3335612 TI - International Neuropsychological Society. 16th annual meeting, January 27-30, 1988, New Orleans, LA. Abstracts. PMID- 3335611 TI - Enhanced production rate of 1,25-dihydroxyvitamin D in sarcoidosis. AB - We determined the metabolic clearance and production rates of 1,25 dihydroxyvitamin D [1,25-(OH)2D] in 5 patients with sarcoidosis who had either hypercalciuria or hypercalcemia to examine whether abnormalities in the metabolism of this hormone existed. The mean MCR in the 5 patients with sarcoidosis [40 +/- 9 (+/- SD) mL/min] was similar to that in 13 normal subjects (37 +/- 6 mL/min) and that in 9 patients with absorptive hypercalciuria and renal stones (35 +/- 4 mL/min). However, the mean serum 1,25-(OH)2D concentration was significantly higher in the patients with sarcoidosis (211 +/- 60 pmol/L) than in either of the other 2 groups. The mean 1,25-(OH)2D production rate was markedly elevated in the patients with sarcoidosis (12.4 +/- 5.3 mumol/day), being more than 2-fold greater than the normal mean value (5.4 +/- 1.2 mumol/day). The highest production rates were found in patients with hypercalcemia, whereas subjects with hypercalciuria had production rates comparable to those in the patients with absorptive hypercalciuria. These data indicate that there is no impairment in the clearance of 1,25-(OH)2D in patients with sarcoidosis and that the elevated serum 1,25-(OH)2D levels are due to an increase in its production rate. PMID- 3335613 TI - International Neuropsychological Society. 16th annual INS meeting. January 27-30, 1988, New Orleans, LA. Abstracts. PMID- 3335614 TI - The Pavlik harness in the treatment of congenital dislocating hip: report on a multicenter study of the European Paediatric Orthopaedic Society. AB - The results of functional treatment using the Pavlik harness in congenital dislocation and congenital dysplasia of the hip in children aged less than 11 months were examined by an EPOS study group. This study was conducted on 3,611 hips in 2,636 patients for a period of 1-9 years after treatment. The reduction rate was 92% in grade Tonnis 2 and 3; the healing rate was 80%. In children with dysplastic hips, the healing rate was 95.35%. Avascular necrosis of the femoral head was observed in 2.38%. The Pavlik harness is designed for outpatient treatment if the parents are compliant. PMID- 3335615 TI - Risk factors of avascular necrosis in the treatment of congenital dislocation of the hip. AB - We examined the causes of iatrogenic avascular necrosis of the femoral head in 254 hips with congenital dislocation (CDH) treated conservatively. The influence of the age of the child, the height of the displacement of the femoral head, the extent of acetabular dysplasia, and the method of treatment on the frequency and degree of necrosis were estimated. The investigation showed that children are at the highest risk of iatrogenic necrosis in the following cases: (a) age less than 6 months, (b) severe acetabular dysplasia, (c) use of an abduction apparatus such as the Frejka pillow for outpatients, and (d) "frog-leg" position after reduction. PMID- 3335616 TI - Comparison of the Frejka pillow and the von Rosen splint in treatment of congenital dislocation of the hip. AB - In southern Finland between 1966 through 1975, 920 newborns were treated with a Frejka pillow for dislocation of the hip. The treatment failed in 55 patients. The pillow was then rejected and replaced with the von Rosen splint. One hundred eighty patients were treated with the new method between 1978 and 1981. The treatment failed in one girl. At 3 years of age, one boy had slight features of avascular necrosis. Temporary skin irritation was found in 19% of patients. In two patients, the splint had to be replaced with a pillow because of skin problems. A treatment device which parents are allowed to take off between outpatient visits is not recommended. PMID- 3335617 TI - Thyroid hormone levels in patients with slipped capital femoral epiphysis. AB - Twelve patients with slipped capital femoral epiphysis and 12 age- and sex matched controls were prospectively studied. Their height, weight, skeletal maturation, and thyroid status were assessed. The duration of symptoms and severity of the slip was recorded in the test group. There was no correlation between duration of symptoms and severity of the slip or delay in making the diagnosis and severity. Although 50 percent of patients with slipped capital femoral epiphysis were over the 90th percentile for weight, there was no overall significant difference in weight, height, or skeletal maturation between the two groups. There was no evidence of either overt or subclinical hypothyroidism in patients with slipped capital femoral epiphysis. PMID- 3335619 TI - Lateral humeral condylar fractures in children: a report of 47 cases. AB - Forty-seven children with fractures of the lateral condyle were reviewed, 4 of whom were treated after a five month delay. The roentgenographic study revealed 4 different types of fractures according to the degree of displacement. Each type corresponded to precise anatomical lesions. In the treatment of recent fractures, we must distinguish between strictly undisplaced fractures, which can be immobilized in a cast, and other fractures, which require open reduction and internal fixation. PMID- 3335618 TI - Our experiences with the early operative treatment of congenital clubfoot. AB - In operative clubfoot therapy, early operation plays an important role. Between 1975 and 1982, we operated on 55 children with 72 clubfeet: 56 posteroplantar releases in patients with an average age of 5.8 months, and 16 posteromedial releases in patients with an average age of 8.1 months. The average follow-up was 3.5 years. The results, based on an investigation scheme according to Henkel, were good and very good in 94%. Operative treatment is indicated after 3 to 4 months of intensive plaster treatment if there has been no further correction. PMID- 3335621 TI - Is the Cotrel-Dubousset really universal in the surgical treatment of idiopathic scoliosis? AB - We reviewed the results of 22 cases of Cotrel-Dubousset (C-D) instrumentation, 16 cases of anterior approach, and 200 cases of posterior approach by Harrington instrumentation and modifications of Harrington procedure. Posterior spinal fusion and instrumentation by C-D gives better correction and stabilization in thoracic and balanced double major curves. We no longer use the Harrington procedure and its modification. In lumbar and short thoracolumbar curves, VDS is still preferred. In some double major curves combined procedures, VDS and C-D are used to obtain more correction with a shorter fusion area. PMID- 3335620 TI - Radial head and neck fractures in children. AB - This report is a review of long-term results of 42 consecutive fractures of the neck of the radius in children. More than half the patients were followed for greater than 4 years. The results were assessed clinically and radiologically at 6 months and at review. Twenty-seven children (64%) had a good result, 2 (5%) had a fair result, and 13 (31%) had a poor result. Primary angulation was the most important factor affecting the results. Periarticular ossification, avascular necrosis, enlargement of the radial head and of the proximal end of the radius were the most important causes of poor results. Unlike other fractures with unpredictable results, more accurate reduction is mandatory to improve the final outcome. PMID- 3335623 TI - Kingella kingae osteoarthritis and osteomyelitis in children. AB - Kingella kingae is still a poorly understood germ which is responsible for osteoarticular infections. We observed nine cases of osteoarthritis involving K. kingae in children. They included 4 cases of arthritis, 2 of osteomyelitis, and 3 of spondylodiscitis. The germ was cultured in all cases by direct surgical approach or by needle aspiration of the septic locus. Evolution was always good after immobilization and nonspecific antibiotherapy. Our nine clinical cases, along with the few cases already published, allow us to state that K. kingae shows a strong affinity for bones and joints in the young child. Clinical presentation is nonspecific. The bacterial sampling must be cultured in enriched atmospheres (CO2). The strains are sensitive to most common antibiotics. PMID- 3335622 TI - Chronic recurrent multifocal osteomyelitis: a follow-up study. AB - Thirteen children/adolescents and two young adults with unifocal or multifocal nonpyogenic inflammatory bony lesions with a prolonged, fluctuating course are reported. The lesions were most often located at the metaphyseal region of tubular bones and the clavicle, but also at the spine, ischiopubic bone, and the sacroiliac joint. Progressive sclerosis and hyperostosis occurred mostly in the clavicle and occasionally in the tibia, femur, metatarsal, and ischiopubic bone, linking the changes to those described under the name Garre osteomyelitis. Seven patients had pustulosis palmoplantaris, and the skeletal disorder may be regarded a form of pustulotic arthroosteitis. PMID- 3335625 TI - Is APD a promising drug in the treatment of severe osteogenesis imperfecta? AB - The efficacy of (3-amino-1-hydroxypropylidene)-1,1-biphosphonate (APD) is reported in a severe case of osteogenesis imperfecta (OI). An increased density at the metaphysis level is demonstrated on wrist radiograph. Similar findings have been observed in two other children with OI at various metaphyseal levels (e.g., tibia, femur). To our knowledge, this is the first time the effect of APD in children with severe OI has been reported. PMID- 3335624 TI - Comparison of different methods of leg lengthening. AB - Corticotomy according to Ilizarov was used for the treatment of congenital leg length discrepancies from June 1984 to June 1986. A comparison of the results of this method and previously performed methods has been made. PMID- 3335626 TI - Effects of triple prevention of CDH, stimulated by distribution of "baby packages". AB - Triple prevention of congenital dislocation of the hip (CDH) consists of screening and earliest treatment in newborns, universal wide diapering in all presumably healthy hips, and repeated screening and early treatment in infants. Preventive activity proved to be decisively stimulated by introduction of "baby packages," containing equipment for wide diapering, which are being distributed to every newborn free of charge. Since the introduction of baby packages, prevalence of CDH dropped from 1.3 to 0.7% despite incomplete distribution. Likewise, incidence of surgery for CDH decreased sevenfold. PMID- 3335627 TI - Hyperlordosis. PMID- 3335628 TI - Autoantibodies to the heat-shock protein hsp90 in systemic lupus erythematosus. AB - Patients with systemic lupus erythematosus (SLE) develop multiple autoantibodies to self-antigens. Analysis of autoantibody systems in this and related autoimmune disorders can provide information of etiologic and pathogenetic significance. We report here a previously unrecognized autoantibody to the 90,000-D heat-shock protein, hsp90, a molecule thought to have important functions in the cellular response to stress, virus-induced transformation, steroid hormone receptor action, and cellular activation. Autoantibodies to hsp90 were exclusively of the IgG class, and were detected in approximately 50% of unselected patients with SLE and 2/6 patients with idiopathic polymyositis. Anti-hsp90 antibodies were not detected in sera from 10 normal subjects, 10 patients with rheumatoid arthritis, or 7 patients with scleroderma. The identity of this major intracytoplasmic antigen was established by its specific removal from nonionic detergent cell lysates following immunoabsorption with monospecific rabbit anti-hsp90, and by demonstration of increased synthesis following a 10-min 45 degrees C heat shock. These data define the frequent occurrence of a novel autoantibody to a major heat shock protein in patients with SLE. PMID- 3335629 TI - Glomerular procoagulant activity in human proliferative glomerulonephritis. AB - Mechanisms for initiation of glomerular fibrin deposition were studied using renal tissue obtained from two patients with rapidly progressive, crescentic glomerulonephritis. Histological examination showed extensive glomerular monocyte infiltration and fibrin deposition in both patients. Sonicated cell suspensions of isolated glomeruli from these patients contained markedly augmented levels of procoagulant activity (PCA) compared with the levels found in normal glomeruli. This PCA was characterized as tissue factor by its functional dependence on Factors VII and V, independence of Factors VIII and XII, inhibition by concanavalin A and phospholipase C, and association with cell membranes. Its coagulant activity was also inhibited by a specific monoclonal anti-human tissue factor antibody. Tissue factor could be identified in glomeruli from these two patients by indirect immunofluorescence using this antibody. These studies implicate extrinsic pathway activation via tissue factor in intraglomerular deposition of fibrin in these patients. Activated monocytes, known to be a potent source of procoagulant activity and seen in large numbers within glomeruli from these patients, are a likely source of this tissue factor. PMID- 3335630 TI - Role of vitamin D-dependent and vitamin D-independent mechanisms in absorption of food calcium. AB - We measured net calcium absorption and the calcium content of the digestive glands secretions in people with widely different serum concentrations of 1,25 dihydroxy vitamin D (hereafter referred to a 1,25-D). Patients with end stage renal disease on hemodialysis served as a model of human 1,25-D deficiency; they were also studied when they had abnormally high serum 1,25-D concentrations as a result of short periods of treatment with exogenous 1,25-D. Normal subjects were studied for comparison. The amount of calcium secreted into the duodenum by the digestive glands was found to be trivial compared to the calcium content of normal or even low calcium meals; therefore, values for net and true net calcium absorption differed only slightly. There was a linear correlation between true net calcium absorption and serum 1,25-D concentration. By extrapolating the short distance to a zero value for serum 1,25-D, D-independent true net calcium absorption was estimated. By subtracting D independent from true net calcium absorption, values for D-dependent absorption were obtained. For a given level of meal calcium intake, D-dependent calcium absorption was found to be directly proportional to serum 1,25-D concentration. At any given value for serum 1,25-D, absorption via the D-dependent mechanism was approximately the same with a low (120 mg) calcium meal as it was when meal calcium intake was increased to 300 mg. We interpret this to mean that the D-dependent mechanism is saturated or nearly saturated by low calcium meals. The D-independent absorption/secretion mechanism resulted in secretion (a loss of body calcium in the feces) when intake was low (120 mg per meal) and absorption when intake was normal. All of the increment in calcium absorption that occurs when low or normal calcium meals are supplemented with extra calcium is mediated by the D-independent mechanism. PMID- 3335631 TI - Reductions of erythrocyte membrane viscoelastic coefficients reflect spectrin deficiencies in hereditary spherocytosis. AB - Hereditary spherocytosis is a common hemolytic anemia associated with deficiencies in spectrin, the principal structural protein of the erythrocyte membrane-skeleton. We have examined 20 different individuals from 10 spherocytosis kindreds and 2 elliptocytosis kindreds to determine the effects of different levels of spectrin deficiency on the viscoelastic properties of the erythrocyte membrane. Micropipettes were used to perform single-cell micromechanical measurements of approximately 1,000 individual cells to determine the membrane elastic shear modulus, the apparent membrane bending stiffness, and whole cell recovery time constant for the different cell populations. The membrane viscosity was calculated by the product of the shear modulus and the recovery time constant. Results show correlation between the fractional reduction in shear modulus and the fractional reduction in spectrin content (determined by spectrin radioimmunoassay) and spectrin density (determined by the ratios of spectrin to band 3 on electrophoresis gels) suggesting that membrane shear elasticity is directly proportional to the surface density of spectrin on the membrane (P less than 0.001). The apparent membrane bending stiffness is also reduced in proportion to the density of spectrin (P less than 0.001). The membrane viscosity is reduced relative to control (P less than 0.001), but the nature of the relationship between spectrin density and membrane viscosity is less clearly defined. These studies document striking relationships between partial deficiencies of erythrocyte spectrin and specific viscoelastic properties of the mutant membranes. PMID- 3335632 TI - Allopurinol enhanced adenine nucleotide repletion after myocardial ischemia in the isolated rat heart. AB - Allopurinol, a competitive inhibitor of xanthine oxidase, has been shown to have a protective effect on ischemic myocardium, but its mechanism of action remains controversial. We used an isolated rat heart preparation to test the hypothesis that allopurinol could restore adenosine triphosphate (ATP) levels and improve the recovery of left ventricular function after global myocardial ischemia. Hearts were equilibrated for 30 min, subjected to 10 min of global, normothermic (37 degrees C) ischemia, and reperfused for 15, 30, and 60 min. Hearts treated with allopurinol (100 microM) exhibited greater ATP levels and improved function during reperfusion than did untreated control hearts. Hearts treated with hypoxanthine (100 microM), the substrate for xanthine oxidase, also showed increased ATP and functional recovery compared with controls. These results suggest that allopurinol may protect the globally ischemic myocardium by enhancing the salvage of hypoxanthine for reincorporation into adenine nucleotides. PMID- 3335633 TI - Iron chelation as a possible mechanism for aspirin-induced malondialdehyde production by mouse liver microsomes and mitochondria. AB - To investigate the possibility that lipid peroxidation is the mechanism responsible for aspirin-induced liver damage, pure neutralized acetylsalicylic acid (ASA), 0.6-90.9 mM, was added to calcium-aggregated mouse liver microsomes followed by incubation in NADPH buffer at 37 degrees C for 60 min and subsequent measurement of malondialdehyde (MDA). MDA production at ASA concentrations from 1.2 to 4.6 mM was greater than control (P less than 0.004). Peak MDA values were observed with 4.6 mM ASA, 39.58 +/- 6.73 nmol MDA/mg protein vs. 16.16 +/- 2.85 (P less than 0.004). Higher concentrations of ASA were inhibitory compared with the value at 4.6 mM (P less than 0.001). Aspirin had similar effects on MDA production by mouse liver mitochondria. MDA production with either ASA or buffer was completely suppressed by the potent iron-chelating agents desferrioxamine and alpha,alpha' dipyridyl when these were added to the microsomal preparations. Since MDA production in this system is known to be affected by iron-chelating agents (enhanced at low concentration, inhibited at higher concentration), the iron-chelating properties of ASA were investigated. Conductivity titration curves of Fe(OH)3 added to water or ASA suggested that the ASA was complexing with iron. The presence of an iron-ASA complex was established by high pressure liquid chromatographic analysis of the solution from this study. We conclude that aspirin enhances MDA production by hepatic microsomes and mitochondria via an aspirin-iron chelate and that this represents at least one mechanism by which aspirin may produce liver damage. PMID- 3335635 TI - KCl co-transport across the basolateral membrane of rabbit renal proximal straight tubules. AB - Mammalian renal proximal tubules reabsorb large amounts of chloride. Mechanisms of the transcellular chloride transport are poorly understood. To determine whether KCl co-transport exists in the basolateral membrane of mammalian renal proximal tubule, isolated rabbit proximal straight tubules (S2 segment) were perfused in vitro, and intracellular activities of potassium and chloride (aKi, aCli) were measured by double-barreled ion-selective microelectrodes. aCli did not change when basolateral membrane voltage was altered by application of a direct current through perfusion pipette. aCli changes in response to bath chloride elimination were not affected by current application as well, indicating that the basolateral chloride transport is electroneutral. An increase in potassium concentration of the bath fluid from 5 to 20 mM reversibly increased aCli by 10 mM. This response of aCli to a change in the bath potassium concentration was also observed when luminal chloride was removed, or ambient sodium was totally removed. aKi significantly decreased by 5 mM when chloride was removed from the bath. These data demonstrate the existence of an electroneutral Na+-independent KCl co-transport in the basolateral membrane of the rabbit proximal tubule. Calculated electrochemical driving force was favorable for the movement of KCl from the cell to the peritubular fluid. PMID- 3335634 TI - Genetic deficiency of short-chain acyl-coenzyme A dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness. AB - Genetic deficiency of short-chain acyl-coenzyme A (CoA) dehydrogenase activity was demonstrated in cultured fibroblasts from a 2-yr-old female whose early postnatal life was complicated by poor feeding, emesis, and failure to thrive. She demonstrated progressive skeletal muscle weakness and developmental delay. Her plasma total carnitine level (35 nmol/ml) was low-normal, but was esterified to an abnormal degree (55% vs. control of less than 10%). Her skeletal muscle total carnitine level was low (7.6 nmol/mg protein vs. control of 14 +/- 2 nmol/mg protein) and was 75% esterified. Mild lipid deposition was noted in type I muscle fibers. Fibroblasts from this patient had 50% of control levels of acyl CoA dehydrogenase activity towards butyryl-CoA as substrate at a concentration of 50 muM in a fluorometric assay based on the reduction of electron transfer flavoprotein. All of this residual activity was inhibited by an antibody against medium-chain acyl-CoA dehydrogenase. These data demonstrated that medium-chain acyl-CoA dehydrogenase accounted for 50% of the activity towards the short-chain substrate, butyryl-CoA, under these conditions, but that antibody against that enzyme could be used to unmask the specific and virtually complete deficiency of short-chain acyl-CoA dehydrogenase in this patient. Fibroblasts from her parents had intermediate levels of activity towards butyryl-CoA, consistent with the autosomal recessive inheritance of this metabolic defect. PMID- 3335636 TI - Mitogenic effects of growth hormone in cultured human fibroblasts. Evidence for action via local insulin-like growth factor I production. AB - We examined human growth hormone's (hGH) effect on mitogenesis in cultured human fibroblasts, and the role of local insulin-like growth factor I (IGF-I). With 0.5% human hypopituitary serum (HPS), hGH increased thymidine incorporation (TI) over serum-free medium dose responsively, with half-maximal effect at 10 ng/ml (0.5 nM) (hGH 127 +/- 8.8%; IGF-I 107 +/- 1.7% [SEM]) (n = 10). Similarly, with 0.5% HPS, hGH and IGF-I increased cell replication by 172 +/- 8.2% and 169 +/- 25%, respectively (n = 4). Specific IGF-I monoclonal antibody (Sm1.2) dose dependently blunted TI stimulated by 10 ng/ml hGH or IGF-I (at 1:1000, 38 +/- 6.5% and 30 +/- 14% reduction, respectively). Sm1.2 also reduced cell replication by both 10 ng/ml hGH and IGF-I, respectively, to 32% and 42% of stimulated values. Dexamethasone (0.1 microM) synergistically enhanced TI by both IGF-I and hGH. A 28-h time course for TI showed that hGH stimulated a similar peak to IGF I, lagging in its effect by 4-10 h. We have provided further evidence that hGH stimulates growth of cultured human fibroblasts via local IGF-I production, consistent with IGF-I's paracrine-autocrine role. PMID- 3335637 TI - Plasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans. AB - We examined plasma levels of the sympathetic neurotransmitter norepinephrine (NE) and its deaminated metabolite dihydroxyphenylglycol (DHPG) during supine rest in healthy human subjects and in sympathectomized patients, during physiological (tilt) or pharmacological (yohimbine, clonidine) manipulations known to affect sympathetically mediated NE release, during blockade of neuronal uptake of NE (uptake-1) using desipramine, and during intravenous infusion of NE. Healthy subjects had a mean arteriovenous increment in plasma DHPG in the arm (10%, P less than 0.05), whereas sympathectomized patients had a mean arteriovenous decrement in DHPG in the affected limb (mean decrease 21%, P less than 0.05 compared with healthy subjects). Tilt and yohimbine, which stimulate, and clonidine, which inhibits, release of endogenous NE, produced highly correlated changes in plasma NE and DHPG (r = 0.94). Pretreatment with desipramine abolished DHPG responses to yohimbine while enhancing NE responses. To attain a given increase in plasma DHPG, about a tenfold larger increment in arterial NE was required during NE infusion than during release of endogenous NE. When plasma NE was markedly suppressed after administration of clonidine, plasma DHPG decreased to a plateau level of 700-800 pg/ml. The results indicate that (i) plasma DHPG in humans is derived mainly from sympathetic nerves; (ii) increments in plasma DHPG during stimulation of NE release result from uptake of NE into sympathetic nerve endings and subsequent intraneuronal conversion to DHPG; (iii) plasma DHPG under basal conditions probably is determined mainly by net leakage of NE into the axonal cytoplasm from storage vesicles; and (iv) increments in NE concentrations at neuronal uptake sites can be estimated by simultaneous measurements of DHPG and NE during NE infusion and NE release. Measurement of NE and DHPG provides unique clinical information about sympathetic function. PMID- 3335638 TI - Source of raised serum estrogens in male rats with portal bypass. AB - We sought to establish the mechanism for the raised serum estrogen levels that occur in male rats with portal hypertension and resultant portal bypass. Using the portal vein ligated (PVL) rat model, we evaluated plasma steroid hormone concentrations, metabolic clearance rate (MCR) of estradiol, and hepatic metabolism of androstenedione to estrogens and other products. In contrast to serum testosterone levels that were reduced, serum androstenedione levels were normal in the PVL rat. Estradiol MCR was measured by a constant intravenous infusion technique and was found to be similar in PVL and control animals. Androstenedione MCR was determined during constant intravenous infusion of [3H]androstenedione, and the resultant radiolabeled steroids present in plasma were separated by thin layer chromatography. The MCR of androstenedione was not diminished in PVL rats compared with controls. However, there was a sevenfold increase in the plasma estradiol derived from [3H]androstenedione in rats with portal bypass. Examination of radiolabel excreted in bile during infusion of [3H]androstenedione showed that 25-46% of this steroid was converted to estradiol in PVL rats compared with less than 3% in control male rats (P less than 0.001). Moreover, there was a selective reduction in the excretion of 16 alpha hydroxyandrostenedione, a finding which suggested that the metabolism of androstenedione via this pathway was decreased. Androstenedione 16 alpha hydroxylation is known to be catalyzed by a male-specific cytochrome P-450 isoform, P-450UT-A. We conclude that raised plasma estradiol levels after portal bypass in male rats are due to increased production rates, resulting in turn from enhanced aromatization of androstenedione to estradiol. On the basis of the observed specific changes in androstenedione hydroxylation pathways, it is proposed that alterations in levels of sex-specific forms of cytochrome P-450 occur in male rats with portal bypass and could account for the enhanced formation of estradiol. PMID- 3335639 TI - Intracellular vacuoles in experimental acute pancreatitis in rats and mice are an acidified compartment. AB - The appearance of vacuoles inside acinar cells characterizes an early stage of development in different models of acute pancreatitis and, possibly, also in human disease. The vacuoles have been shown to contain both digestive and lysosomal enzymes. This abnormal admixture may have important implications for the pathogenesis of pancreatitis because the lysosomal enzyme cathepsin B can activate trypsinogen and may, by this way, trigger pancreatic autodigestion. For the activation process of trypsinogen by cathepsin B, however, an acidic pH is required. This study, therefore, looked for evidence of vacuole acidification in two different models of acute pancreatitis. Edematous pancreatitis was induced in rats by hyperstimulation with cerulein and hemorrhagic pancreatitis was induced in mice by feeding a choline-deficient, ethionine-supplemented diet. Pancreatic acinar cells were isolated at different times after induction of pancreatitis and incubated with 50 microM of acridine orange to identify acidic intracellular compartments. As shown in previous work, zymogen granules are the main acidic compartment of normal acinar cells; they remained acidic throughout the course of pancreatitis in both models. Vacuoles became increasingly more frequent in both models as pancreatitis progressed. Throughout development of pancreatitis, vacuoles accumulated acridine orange indicating an acidic interior. Addition of a protonophore (10 microM monensin or 5 microM carbonyl cyanide m chlorophenylhydrazone [CCCP] or a weak base (5 mM NH4Cl) completely and rapidly abolished acridine orange fluorescence inside both zymogen granules and vacuoles providing further evidence for an acidic interior. The acidification of vacuoles seen in two different models of pancreatitis may be an important requirement for activation of trypsinogen by cathepsin B and thus for the development of acute pancreatitis. PMID- 3335640 TI - Human erythrocyte protein 4.1 is a phosphatidylserine binding protein. AB - The aminophospholipids phosphatidylethanolamine (PE) and phosphatidylserine (PS) are the major phospholipids contained in the cytoplasmic leaflet of the human erythrocyte (RBC) plasma membrane and are largely confined to that leaflet over the entire RBC lifespan. In particular, PS, which comprises approximately 13% of total RBC membrane phospholipids, is normally restricted entirely to the cytoplasmic leaflet. However, molecular mechanisms that regulate this asymmetric distribution of phospholipids are largely unknown. We examined elliptocytic RBCs that completely lacked protein 4.1 (HE [4.1 degrees]), but contained normal amounts of all other peripheral membrane proteins, and found approximately 10% of total membrane PS was accessible in the exoplasmic leaflet of these membranes. Inside out vesicles (IOVs) derived from HE [4.1 degrees] RBCs bound fewer PS liposomes than did IOVs derived from normal RBCs. Normal IOVs that were depleted of proteins 2.1 (ankyrin), 4.1, and 4.2 bound fewer PS liposomes similar to HE [4.1 degrees] IOVs, and repletion with protein 4.1 restored PS liposome binding to control levels. Addition of purified protein 4.1 to PS liposomes resulted in saturable binding with the extent of binding being proportional to the liposome PS content. Our data suggests that human RBC protein 4.1 is a PS binding protein and may be involved in the molecular mechanisms that stabilize PS in the cytoplasmic leaflet of the human RBC plasma membrane. PMID- 3335641 TI - Modulation of conduction and refractoriness in atrioventricular junctional reentrant circuit. Effect on reentry initiated by atrial extrastimulus. AB - The importance of activation sequence of an atrioventricular junctional reentrant (AVJRe) circuit, before delivery of an extrastimulus, has received little attention in studies concerned with clinical tachycardias. In this study a change in activation sequence was accomplished using bidirectional activation (V-A sequential pacing) during the basic drive (V1A1-V1A1). It was noted that, compared with an atrial extrastimulus (A2) after an atrial drive (A1-A1), earlier activation (by V1 impulse of the V1A1-V1A1 drive) consistently improved conduction, or decreased refractoriness, or both, in the anterograde as well as the retrograde pathway of the AVJRe circuit. In all patients, five with AV nodal reentry and six with Wolff-Parkinson-White syndrome, reentrant tachycardia could be prevented during V-A sequential pacing. In four of eleven patients, reentry was prevented despite achieving the so-called critical atrioventricular nodal delays that had previously caused reentry during control study. This finding suggested that conduction delay necessary for reentry was related to the site of block, which in turn was affected by V-A sequential pacing. We concluded that changing the activation sequence during basic drive modulates conduction and refractoriness in AVJRe circuits, and allows the study of a wide range of electrophysical factors that prevent or permit reentry. PMID- 3335642 TI - Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. AB - Severe neurotoxicity due to 5-fluorouracil (FUra) has previously been described in a patient with familial pyrimidinemia. We now report the biochemical basis for both the pyrimidinemia and neurotoxicity in a patient we have recently studied. After administration of a "test" dose of FUra (25 mg/m2, 600 microCi[6-3H]FUra by intravenous bolus) to a patient who had previously developed neurotoxicity after FUra, a markedly prolonged elimination half-life (159 min) was observed with no evidence of FUra catabolites in plasma or cerebrospinal fluid and with 89.7% of the administered dose being excreted into the urine as unchanged FUra. Using a sensitive assay for dihydropyrimidine dehydrogenase in peripheral blood mononuclear cells, we demonstrated complete deficiency of enzyme activity in the patient and partial deficiency of enzyme activity in her father and children consistent with an autosomal recessive pattern of inheritance. Patients who are deficient in this enzyme are likely to develop severe toxicity after FUra administration. PMID- 3335643 TI - Role of platelets in cholesteryl ester formation by U-937 cells. AB - The conversion of tissue macrophages into cholesteryl ester-rich foam cells is a crucial early event in atherogenesis. We studied the platelet as a potential source of cholesterol for esterification by macrophages because (a) platelets are rich in free cholesterol, (b) they adhere to macrophages early in atherogenesis, and (c) vascular injury can induce foam cell formation in the absence of hyperlipoproteinemia. We found that washed, activated human platelets from normocholesterolemic donors stimulated cholesteryl ester formation by the human monocyte-derived cell, U-937. Platelet cholesterol, released from platelets activated with calf skin collagen, was approximately equipotent at donating cholesterol to U-937 cells for esterification as normal human low density lipoprotein cholesterol. The stimulation of cholesteryl ester formation by activated human platelets demonstrated both concentration and time dependence. When hypercholesterolemic donors were studied, it was found that increasing plasma levels of cholesterol correlated directly with the ability of these hypercholesterolemic platelets to support cholesteryl ester synthesis by U-937 cells. Cholesterol-donating activity was also found in a 1,000-g supernatants of activated platelets. These observations point to a new and potentially important role for platelets in atherogenesis and suggest a mechanism for foam cell formation in the absence of marked hypercholesterolemia. PMID- 3335644 TI - N-desulfated/acetylated heparin ameliorates the progression of renal disease in rats with subtotal renal ablation. AB - The effect of administration of N-desulfated/acetylated heparin, almost completely devoid of anticoagulant activity, on the progression of renal disease was examined in rats with 13/4 nephrectomy. Three groups of rats with 13/4 nephrectomy were studied. Group I (control, n = 11) received 0.15 ml of 0.15 M NaCl subcutaneously twice daily for 5 wk; group 2 (n = 11) received 0.15 ml twice daily of N-desulfated/acetylated heparin (5.4 mg/ml; less than 0.5 U/ml); group 3 (n = 9) received 0.15 ml twice daily of standard beef lung heparin (5.4 mg/ml; 977 U/ml). Clearances and renal histological studies were done at the end of 5 wk of heparin or saline administration. Rats given the heparin preparations had significantly higher inulin clearances (2.55 +/- 0.38 ml/min per body weight (BW) for group 2, or 2.60 +/- 0.24 ml/min per kg BW for group 3) than control rats (1.59 +/- 0.20 ml/min per kg BW). Histological analysis revealed a greater number of glomeruli with segmental or global sclerosis, hyalinosis, or fibrosis (36.6%) in control rats than in rats receiving N-desulfated/acetylated heparin (6.2%) or standard heparin (3.0%). Blood pressure averaged 169.4 +/- 6.2 mmHg in controls, 119.1 +/- 6.1 in rats of group 2, and 124.3 +/- 2.5 in rats of group 3. The values for blood pressure were significantly lower in the two groups receiving heparin than in controls. These studies indicate that a heparin preparation, almost completely devoid of anticoagulant properties, affords the same degree of protection against progression of renal disease as does standard heparin in rats with subtotal renal ablation. It is suggested that other biological properties of heparin may be responsible for the effects observed. PMID- 3335645 TI - Unregulated proliferation of primitive neoplastic progenitor cells in long-term polycythemia vera marrow cultures. AB - Marrow cells from seven untreated patients with polycythemia vera (PV) were used to initiate standard single inoculum long-term marrow cultures. The numbers, erythropoietin independence, and cycling behavior of all detectable classes of erythroid, granulopoietic, and multilineage progenitors were then evaluated and the results obtained compared with preculture values. Time course studies showed that the long-term marrow culture system supports the continuous proliferation of primitive neoplastic progenitor cells from PV patients for many weeks. However, these progenitors fail to respond to signals from the adherent layer that return their counterparts in normal long-term marrow cultures to a quiescent state 5-7 d after each medium change. This abnormal cycling behavior of PV cells in the long term culture system appears to mimic that operative in vivo, where primitive hemopoietic progenitors are also in a continuous state of turnover, in contrast to similar primitive progenitor compartments in normal individuals, which are quiescent. The long-term marrow culture system thus offers new possibilities for the further analysis of abnormal cellular and molecular mechanisms underlying clonal expansion at the stem cell level in PV. PMID- 3335646 TI - Eigenimage filtering in MR imaging. AB - This article presents the technical aspects of a linear filter, referred to as eigenimage filtering, and its applications in magnetic resonance (MR) imaging. The technique is used to obtain a single composite image depicting a particular feature of interest while suppressing one or more interfering features. The appropriate weighting components to be used in the linear filter are determined on the criterion that the desired feature is enhanced while the interfering features are suppressed. The criterion is expressed mathematically as a ratio. By applying Rayleigh's principle, the ratio is maximized by finding the eigenvector associated with the maximum eigenvalue of the corresponding generalized eigenvalue problem. The appropriate weighting factors for the linear filter are the elements of the eigenvector which maximize the ratio. The utilization of the technique is demonstrated in its application to a simulated MR image sequence as well as to acquired MR image sequences of a normal and an abnormal brain. PMID- 3335647 TI - Neonatal brain tumors: CT and MR findings. AB - Twelve neonatal brain tumors, presenting within 60 days of birth, constituted 3.3% of pediatric brain tumors. Three-fourths were supratentorial. Two-thirds were benign. Forty-two percent were choroid plexus papilloma. Twenty-five percent were teratoma. Eight percent each were hypothalamic glioma, gliosarcoma, medulloblastoma, and primitive neuroectodermal tumor. Clinical symptoms were nonspecific. Signs of herniation were absent in all 12 patients. Forty-two percent of these patients died 1 day to 8 months after diagnosis. Ultrasound, CT, and magnetic resonance have all proved useful for displaying these lesions suitably for surgery. PMID- 3335649 TI - MR imaging of chronic osteomyelitis. AB - Magnetic resonance (MR) at 1.5 T was used preoperatively and prior to aspiration to determine extent and location of infection in eight patients with chronic osteomyelitis. There was excellent correlation between MR and surgical findings in all cases. Infected areas, both intraosseous and extraosseous, displayed increased signal intensity on T2-weighted images. Sequestra, sinus tracts, and soft tissue abscesses were seen. By directly imaging foci of infection MR may have certain advantages over CT and scintigraphy in the evaluation of chronic osteomyelitis. PMID- 3335648 TI - Infected aortic aneurysms: CT appearance. AB - Three patients with infected (mycotic) aortic aneurysms were diagnosed primarily by CT. In two patients findings included the presence of a saccular aneurysm with an irregular lumen, perianeurysmal fluid, gas and/or hematoma, osteomyelitis in adjacent vertebral bodies, and disruption of intimal calcification. In one patient with sepsis there was rapid development of an aortic aneurysm. Computed tomography is of substantial benefit in the identification and characterization of infected aortic aneurysms. Certain features may strongly suggest the diagnosis without use of aortography. PMID- 3335650 TI - MR flow imaging in projection through a stationary surround. AB - A magnetic resonance imaging technique is discussed which, by cyclic inversion of the longitudinal magnetization, produces boli of moving material with alternating sign of the magnetization. At periodic spacings along the flow direction, the signal strength from magnetization of positive sign is equal to that of negative sign. This results in a minimum in the intensity distribution. A banded intensity structure results reflecting the distribution of flow velocities across the imaged vessel. The inversion of the longitudinal magnetization causes an inherent suppression of the signal from stationary material allowing the collection of flow images in projection through a stationary surround without the need for image subtraction. PMID- 3335651 TI - An index system for comparative parameter weighting in MR imaging. AB - An analytic method for comparative parameter weighting in magnetic resonance (MR) imaging has been developed using the concept of "fractional sensitivity." This new approach results in easily calculated indexes for T1, T2, and hydrogen weighting. This index system enables quantitative comparisons to be made between MR studies that have been performed at various field strengths, using different pulse sequences and pulse timing intervals. PMID- 3335652 TI - Post-traumatic diabetes insipidus: MR demonstration of pituitary stalk rupture. AB - We report the magnetic resonance findings in a case of post-traumatic diabetes insipidus (DI). They consisted of pituitary stalk rupture shown on both coronal and sagittal planes with associated disappearance of the normal high signal intensity of the posterior lobe on T1 images. This last sign, previously described in nontraumatic DI, appears to represent a finding indicating nonfunctioning neurohypophysis. PMID- 3335653 TI - Cavernous sinus air in a patient with basilar skull fracture: CT identification. AB - Air within the cavernous sinus resulting from fracture of the wall of the sphenoid sinus was identified by cranial CT in a patient with head injury. Careful search of the skull base is important in post-traumatic pneumocephalus to identify a potential site of CSF leak. PMID- 3335654 TI - Ewing sarcoma of the skull with an unusual pattern of reactive sclerosis: MR characteristics. AB - A case of primary Ewing sarcoma involving the occipital bone with an unusual radiographic feature--markedly thickened bone--is described. Magnetic resonance imaging was more helpful than CT in determining the lesion extent due to lack of bone artifact and since it showed the precise relationship of the neoplasm to the tentorium on direct coronal imaging. PMID- 3335655 TI - MR imaging of traumatic diaphragmatic rupture. AB - The diagnosis of traumatic rupture of the diaphragm may remain elusive despite a variety of imaging options including CT and sonography. Direct sagittal and coronal magnetic resonance images provided a definitive diagnosis of left diaphragmatic rupture with herniation of colon into the thorax. PMID- 3335656 TI - Unusual presentation of cholelithiasis on T1-weighted MR imaging. AB - Cholelithiasis usually appears on magnetic resonance as a signal void contrasting with the high signal of surrounding bile. We describe the appearance of two intraluminal gallstones as high-signal areas on a heavily T1-weighted scan and, based on infrared spectroscopic analysis of the stones, believe the fatty-acid content of the stones accounts for this unusual result. Increased focal intraluminal signal on strongly T1-weighted sequences does not, therefore, preclude a diagnosis of cholelithiasis. PMID- 3335658 TI - Computed tomography of the kidneys in a patient with methoxyflurane abuse. AB - Methoxyflurane, a general anesthetic, is a known nephrotoxin. A case is presented that demonstrated diffuse, bilateral renal cortical calcification on CT secondary to repeated methoxyflurane inhalation. PMID- 3335657 TI - Right adrenal pseudotumor caused by colon: CT demonstration. AB - Multiple adrenal pseudotumors have been previously described on CT and routine radiography. In the following case report we demonstrate interposition of normal colon between the liver, kidney, and adrenal in the hepatorenal recess that produced the CT appearance of a pseudotumor of the right adrenal gland. PMID- 3335659 TI - Non-Hodgkin lymphoma of ureteral wall: CT findings. AB - We report a case of focal ureteral wall non-Hodgkin lymphoma without contiguous or other associated abdominal abnormalities. The CT findings and the differential diagnosis are discussed. PMID- 3335661 TI - MR imaging of pregnancy in bicornuate uterus. AB - We report a case of incarcerated bicornuate pregnancy diagnosed by magnetic resonance. In this unusual case both CT and sonography suggested an abdominal pregnancy. Magnetic resonance may be a valuable adjunct to sonography in the management of the complicated pregnancy in spite of nonvisualization of the fetal parts due to fetal movement. PMID- 3335660 TI - Retroperitoneal fibrosis presenting as colonic dysfunction: CT diagnosis. AB - In a patient who presented with pelvic pain and changed bowel habits, barium enema and sigmoidoscopic examinations demonstrated a nonspecific asymmetric narrowing of the colon at the rectosigmoid junction with normal mucosal appearance. Computed tomography revealed the etiology to be retroperitoneal fibrosis with pelvic extension and entrapment of the colon at this level. The importance of CT in diagnosis of this unusual manifestation of retroperitoneal fibrosis is discussed. PMID- 3335662 TI - MR imaging of anterior sacral meningocele. AB - The magnetic resonance appearance of a case of an anterior sacral meningocele is described and the particular advantages of this technique, compared with other radiological studies, are considered. PMID- 3335663 TI - Basal ganglia lesions in methanol poisoning: MR appearance. PMID- 3335664 TI - CT and MR appearance of a primary intraosseous meningioma. PMID- 3335665 TI - Initial experience with fast low-angle multiecho (FLAME) imaging of the central nervous system. AB - Fast low-angle multiecho (FLAME) imaging uses partial flip angles of less than 90 degrees with 180 degrees radiofrequency refocusing pulses. The partial flip angle permits imaging with shorter repetition time (TR) values on the order of 750 1,000 ms for 30 degrees angles with image contrast characteristics identical to those obtained with conventional 90-180 degrees schemes and TRs on the order of 2,500 ms. The approximately threefold reduction in imaging time is accompanied by a decrease in signal-to-noise ratio. In many circumstances, however, this trade off may produce entirely acceptable images of the CNS at a significant reduction in imaging time. PMID- 3335666 TI - Holography of 3D surface reconstructed CT images. AB - A multiplex hologram (cylindrical holographic stereogram) was successfully made from three-dimensional (3D) surface reconstruction CT images of a child with plagiocephaly. This method appears to be suitable as one of the projectional aids of 3D surface reconstruction CT images that are proving useful in plastic and reconstructive surgery. The principle of the method is described. Also discussed is the possibility of developing a computer-aided hologram synthesizing system that could be used for images obtained with U-arm X-ray equipment (by either cinefilm, or videotape, or digital subtraction angiography) or by CT as well as MR. For practical use, it is necessary for the hologram to be synthesized in a short time. One of the key problems in developing such a machine is the need for an incoherent-to-coherent image converter. PMID- 3335667 TI - Temporal lobe volume measurement from MR images: accuracy and left-right asymmetry in normal persons. AB - The effect of several magnetic resonance (MR) variables on the accuracy of volume measurements in phantom objects was investigated by use of an off-line automatic border-outlining and internal area pixel-counting computer program, and an optimal set of imaging variables was identified. Measurements were made of the temporal lobe volumes of a gross fixed brain specimen from MR image data. The range in accuracy was from -2 to +7%, and the standard deviation of the difference in right minus left lobe volume measurements obtained from the MR images and those obtained by use of Archimedes' principle was 1 cm3. This volumetric technique was applied to 25 normal persons, most of whom were right handed. The median ratio of right to left temporal lobe volume was 1.16 (range 0.99-1.23). The nondominant temporal lobe was significantly larger than the dominant. The mean difference (95% confidence interval) between right and left volumes was 7 cm3 (6-9 cm3). This confidence interval was similar to that obtained when the variability within a subject (estimated from the gross fixed brain specimen) was taken into account. Unilateral temporal lobe atrophy, particularly in patients with temporal lobe epilepsy, should be interpreted from MR images with this range of discrepancy in normal left-right size in mind. PMID- 3335668 TI - MR imaging of unusual chordomas. AB - Chordomas are uncommon primary skeletal neoplasms arising from notochordal remnants. Approximately 50% arise in the sacrum, 35% in the clivus, and less than 15% in the true vertebrae. We report magnetic resonance (MR) studies of four unusual primary chordomas, three in the lumbar region (L1, L2, and L3) and one in the Meckel cave. It is often difficult to differentiate the MR findings of these four tumors from other common neoplasms. PMID- 3335670 TI - Leigh disease (subacute necrotizing encephalomyelopathy): CT and MR in five cases. AB - Magnetic resonance (MR) imaging and CT were used in supporting the diagnosis of Leigh disease (subacute necrotizing encephalomyelopathy) in five patients. Two cases were confirmed at postmortem examination, and three patients have laboratory and/or clinical histories suggestive of Leigh disease. Four cases demonstrated findings in the basal ganglia, especially the putamina, with symmetrical areas of low attenuation on CT. Correspondingly, on proton saturation and T2-weighted pulse sequences, these areas showed high intensity signal characteristics by MR. Similar findings were noted in the caudate nucleus (two cases). Magnetic resonance proved to be superior to CT in establishing other areas of involvement: tectum and tegmentum (one case) and medullary olive (one case). Pathology identified these lesions as representing necrosis. Magnetic resonance may be diagnostic in the appropriate clinical setting. PMID- 3335669 TI - Is cranial CSF volume under hormonal influence? An MR study. AB - We used magnetic resonance to investigate the hypothesis that premenstrual neurological symptoms are due to cerebral oedema and brain swelling. Total cranial and lateral ventricular CSF volumes were measured midcycle and premenstrually in 20 women with a normal menstrual cycle, and similar measurements were made 2 weeks apart in 10 postmenopausal women and 10 men. Total cranial CSF volume increased premenstrually in 19 women. The mean premenstrual increase was by 11.5 ml. There was not a significant difference between those women who were taking an oral contraceptive and those who were not. The CSF volume did not change significantly on repeat measurement in men and postmenopausal women. The CSF changes observed reflect a reduction in brain volume and do not support cerebral swelling as the cause of premenstrual neurological symptoms. PMID- 3335671 TI - Pontine calcification following radiotherapy: CT demonstration. AB - Development of pontine calcifications following radiation therapy for suprasellar tumors is described in two patients, 5 and 9 years old. Post-radiotherapy brain calcifications are rare in the brain stem. PMID- 3335672 TI - CT demonstration of extraocular muscle atrophy. AB - Two cases of CT-documented extraocular muscle atrophy are presented. Unilateral atrophy was observed in a patient with a lesion of the cavernous sinus. Atrophic extraocular muscles were noted bilaterally in a young woman with "ophthalmoplegia plus" (probable Kearns-Sayre syndrome). PMID- 3335673 TI - Hyperostotic esthesioneuroblastoma: CT and MR findings. AB - Olfactory neuroblastoma is a malignant, slow growing, neurogenic tumor that originates in the olfactory mucosa of the upper nasal cavity. Its CT appearance, i.e., a soft tissue mass adherent to the cribriform plate usually with bone lysis, has been described. Two cases are presented in which this entity was associated with exuberant bony hyperostosis, a feature not previously reported. The differential diagnosis of nasoethmoid soft tissue masses with associated hyperostosis is reviewed. PMID- 3335674 TI - Median cleft face syndrome: MR and CT data from 11 children. AB - Examination (including CT and magnetic resonance studies) of 11 unrelated children with median cleft face syndrome revealed 6 (55%) with dense calcification of the falx and 5 (45%) with interhemispheric lipoma. Of the 11 children, 3 exhibited Sedano facies type A, 4 exhibited Sedano facies type B, and 4 exhibited Sedano facies type D. Type A patients had no calcification or lipoma. Two of three type A patients were products of separate twin gestations, the only twins in the series. Type B patients had frequent falx calcification (three of four) and interhemispheric lipoma (two of four). Two of the four type B patients had concurrent Goldenhar syndrome, the only such patients in the series. Type D patients also had frequent falx calcification (three of four) and interhemispheric lipoma (three of four). Patients with median cleft face syndrome and Sedano facies type B or D should be examined radiologically for concurrent intracranial pathology. PMID- 3335675 TI - MR imaging of the thorax: a comparison of axial, coronal, and sagittal imaging planes. AB - We performed direct multisection coronal and sagittal magnetic resonance (MR) images in addition to axial images to determine the value and limitations of coronal and sagittal planes compared with axial planes. Ninety-four MR examinations of the thorax were performed with a 0.3 T permanent magnet system (Fonar) by spin echo technique. The MR axial images were found superior to coronal in demonstrating prevascular adenopathy (one case), pretracheal nodes (nine cases), left paraaortic nodes (three cases), subcarinal nodes (three cases), and small pleural effusions (three cases). The coronal or sagittal planes were better to determine relationship of a mass at the lung apex (five cases) or an abnormality at the lung base (five cases). The anteroposterior displacement or compromise of great vessels and bronchi was best displayed on the axial plane whereas craniocaudal displacement of above structures was best seen on the coronal plane. The axial images were found most informative and we suggest that they be performed routinely. Coronal or sagittal planes may be added in selected cases. PMID- 3335676 TI - CT findings in gastrointestinal perforation by ingested fish bones. AB - Preoperative diagnosis of complications due to foreign bodies in the gastrointestinal tract is uncommon by conventional radiographic methods. We present two cases of gastric and duodenal perforation secondary to fish bone ingestion, diagnosed preoperatively by CT. PMID- 3335677 TI - MR evaluation of liver iron overload. AB - Children and young adults with hemolytic anemias requiring frequent transfusions develop increased liver iron content. We evaluated 15 chronically transfused children with sickle cell disease to determine whether spin-echo magnetic resonance (MR) imaging was useful in assessing the degree of iron overload. Quantitative MR parameters were correlated with liver biopsy iron determinations and serum ferritin levels. The best predictor of liver iron was the ratio of the intensities between the liver and paraspinal musculature on somewhat T1 weighted sequence (repetition time 0.5 s, echo time 28 ms), R2 = 0.58. Magnetic resonance was able to separate those patients with liver iron levels greater than 100 micrograms/mg (intensity ratios approximately 0.4), from those with levels less than 100 micrograms/mg (intensity ratios near 1). However, MR was unable to quantitate liver iron in patients with values ranging from 100 to 400 micrograms/mg since similar intensity ratios were present in this range. Thus, MR provides a qualitative rather than quantitative assessment of liver iron overload. PMID- 3335678 TI - MR imaging of urinary bladder neoplasms. AB - The diagnostic potential of magnetic resonance (MR) imaging at 1.5 T for assessment and staging of urinary bladder tumors was investigated in 10 patients with malignant urinary bladder tumors. All patients underwent complete pathologic staging. The appearance of the urinary bladder tumors and the ability to stage them by means of MR imaging was evaluated morphologically and compared with results obtained with pathologic examination. Magnetic resonance imaging permitted tumor localization in all patients. In nine patients the tumor stage was accurately determined by MR imaging. The smallest tumor detected by MR imaging was 1.5 cm. Both transverse and sagittal imaging planes were found to be essential for accurate assessment of tumor extension. Signal intensity data obtained from both dual and multi spin echo sequences showed that tumor display and depth of infiltration was best seen with a repetition time (TR) of 2,000 ms and an echo time (TE) of 90 ms. Accurate evaluation of perivesical tumor infiltration required a sequence with a TR 800 ms and a TE 30 ms. Data presented here further support the role of MR in staging urinary bladder neoplasms. PMID- 3335679 TI - Wood's lamp and surgical margins in malignant melanoma in situ. PMID- 3335680 TI - Merkel cell carcinoma. PMID- 3335681 TI - Flat fixation technique for shave biopsy specimens: stick & shake. AB - Curling of thin-shaved biopsy specimens is not uncommon in formalin-fixed tissue. The distorted tissue may cause improper orientation, with subsequent tangential sections by the histotechnician and misinterpretation by the pathologist. We describe a simple "stick & shake" fixation technique, performed by the surgeon at the time of shaving, which flattens the biopsy specimen, and thus reduces the possibility for curling. This technique is especially useful in the interpretation of difficult neoplasms, where visualization of the periphery (shoulders) is crucial for accurate diagnosis, e.g., dysplastic melanocytic nevi. PMID- 3335682 TI - Transplantation of human basal cell carcinoma to C57/BALB/C bgJ/bgJ-nu/nu (beige nude) mouse. AB - The purpose of this study was to evaluate the transplantation of BCC to the C57/BALB/C bgJ/bgJ-nu/nu (beige-nude) mouse. This animal has two gene defects which are expressed as impairment of natural killer cells (NK cells) as well as the absence of a thymus. The results demonstrate that human BCC can be successfully transplanted to the C57 beige-nude mouse without the need for supplemental immunosuppression. It may be that the impairment of NK cell activity in the beige-nude mouse model plays a significant role in tumor transplantation. PMID- 3335683 TI - Combined scalp reduction and autologous fat implant treatment of localized soft tissue defects. AB - Autologous fat grafts have recently gained popularity in the treatment of soft tissue defects of the face. We report on two patients with circumscribed scalp alopecia and linear forehead depressions treated with a combination of scalp reduction and autologous fat implants. The patients had significant cosmetic improvement without complications. PMID- 3335684 TI - The modified major scalp reduction. AB - A new procedure for reducing the area of baldness, the modified major scalp reduction, is presented. This operation provides an important alternative to either standard or major scalp reductions. The surgical technique is described in detail, and comparisons are made with regard to advantages and disadvantages. PMID- 3335685 TI - Linear atrophy following intralesional steroid injections. AB - Two cases of perilymphatic atrophy following correctly administered intralesional steroid injections are reported. Perilymphatic atrophy produces a distinct clinical picture and may persist for months. A review of the literature shows that no treatment is indicated. It is stressed that the appearance of this cosmetically disturbing side effect is unpredictable, but spontaneously reversible. PMID- 3335686 TI - Quantitation of day to day variability in mode of induction of ventricular tachyarrhythmias by programmed stimulation. AB - Spontaneous day to day variability in the mode of induction of ventricular tachycardia at programmed stimulation in the drug-free state has been described but not quantitated. To quantitate this variability, this study employed a new protocol of programmed stimulation in which the number of extrastimuli required for tachycardia induction was the only major stimulation variable. This protocol was applied to 18 consecutive patients with previously documented sustained ventricular tachyarrhythmia due to coronary artery disease. One to seven extrastimuli were available for arrhythmia induction if required. Each patient underwent programmed stimulation in the absence of antiarrhythmic drugs on 3 separate days with a mean interval of 5 +/- 2.7 days between studies. A sustained ventricular tachyarrhythmia was inducible in all studies with less than or equal to 4 extrastimuli; the mean number of extrastimuli required was 2.4 +/- 0.8. Day to day variability in the number of extrastimuli required for tachycardia induction was observed in the majority of patients (72%). Eleven patients (61%) varied by one extrastimulus over the three control studies, and two patients (11%) varied by two extrastimuli. At analysis of variance, the 95% confidence interval for the degree of day to day variability was +/- 1 extrastimulus from the mean number required in the three studies. Multiple configurations of induced ventricular tachycardia were frequently observed at repeat studies and occurred in 15 patients (83%). In conclusion, spontaneous day to day variability in mode of induction of ventricular tachycardia in the absence of drugs is common.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335687 TI - Region of slow conduction in sustained ventricular tachycardia: direct endocardial recordings and functional characterization in humans. AB - Direct endocardial recording from a discrete region of slow conduction in the left ventricle was performed in a patient during sustained ventricular tachycardia. The tachycardia had a right bundle branch block and superior axis configuration with the earliest site of endocardial activation in the posterolateral left ventricle. At this site, the left ventricular electrogram during the tachycardia displayed two deflections with distinctly different responses to rapid pacing. During rapid pacing from the right ventricular apex, one deflection was transiently entrained, representing activation of the ventricle distal to a region of slow conduction in the reentrant circuit. However, the other deflection was not entrained and arose from activation proximal to this region. At a critically rapid pacing rate, interruption of the tachycardia was associated with conduction block in the region of slow conduction, as demonstrated by dissociation of the two deflections on the posterolateral left ventricular electrogram. At pacing rates that transiently entrained but did not terminate the tachycardia, decremental properties of conduction were demonstrated in the region of slow conduction, but not in the rest of the reentrant circuit. These responses of the posterolateral left ventricular electrogram to pacing during ventricular tachycardia strongly suggest that the recordings bracketed a discrete region of slow conduction in the left ventricle that was critical for the maintenance of ventricular tachycardia. Furthermore, these data demonstrate that this region of slow conduction in the left ventricle had decremental conduction properties and was the site of block during rapid pacing at rates sufficient to interrupt the tachycardia. PMID- 3335688 TI - Amiodarone therapy: role of early and late electrophysiologic studies. AB - Forty-two patients with a history of symptomatic ventricular tachycardia or cardiac arrest underwent electrophysiologic testing at control and early in the course of amiodarone therapy (mean 12 +/- 7 days). Late electrophysiologic studies (mean 17 +/- 4 weeks) were repeated in 23 patients on a maintenance dose of 400 mg/day. At control study, all patients had inducible ventricular tachyarrhythmias (sustained ventricular tachycardia in 35, nonsustained ventricular tachycardia in 4, ventricular fibrillation in 3), while after amiodarone loading (1,200 mg daily) 4 (10.5%) of the 42 patients developed noninducible ventricular arrhythmias. At late study, an additional 6 (26%) of the 23 patients with inducible arrhythmias at early study developed noninducible arrhythmias. The cycle length of induced ventricular tachycardia increased from 275 +/- 61 ms at control study to 340 +/- 58 ms at early study (p = 0.001). A further increase in ventricular tachycardia cycle length was noted in patients who underwent both early and late study (341 +/- 38 versus 375 +/- 63 ms, p less than 0.05). The percent of induced tachycardias that were clinically tolerated increased as patients were treated longer with amiodarone (control = 22%, early = 34%, late = 53%, p less than 0.001). Of the 23 patients who had both early and late electrophysiologic studies and were followed up for a mean of 21.7 months (range 4 to 47), there were no recurrences among the 6 patients with noninducible arrhythmias, but there were five recurrences among the 17 patients with persistently inducible arrhythmias. None of the four patients with noninducible arrhythmias at early study had a recurrence. On the basis of these findings, it is concluded that: 1) The timing of programmed electrical stimulation will affect the results of the study in patients treated with oral amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335689 TI - Time course of left ventricular dilation after myocardial infarction: influence of infarct-related artery and success of coronary thrombolysis. AB - Dilation of the left ventricle after myocardial infarction is common, occurs rapidly (within 2 weeks of infarction) and may be self-limited. To evaluate the time course of postinfarction left ventricular dilation and to assess the impact of successful coronary thrombolysis, serial radionuclide left ventricular volume analyses were performed in 36 patients undergoing attempted thrombolysis for acute transmural myocardial infarction. All patients underwent cardiac catheterization, coronary angiography and attempted thrombolysis within 7 h of the onset of symptoms. The site of coronary occlusion was the left anterior descending coronary artery in 17 patients, the right coronary artery in 18 and, in 1 patient, occluded bypass grafts to the right and left circumflex coronary arteries. Attempted reperfusion using a thrombolytic agent was successful in 22 individuals, occurring 5 +/- 1 h after the onset of symptoms. Gated radionuclide ventriculography was performed early (mean time 1 day after admission, n = 36), subacutely (mean time 11 days postinfarction, n = 36) and late after infarction (mean time 10.5 months, n = 25), and a geometric technique was used to measure serial left ventricular end-diastolic volume. Left ventricular end-diastolic volume for the entire group increased significantly (p less than 0.01) from 153 +/- 30 ml at baseline to 172 +/- 45 ml (at 11 days) to 220 +/- 63 ml (at 10.5 months). Twenty of 36 patients showed greater than 20% increase in left ventricular end-diastolic volume (dilation) with time. This appeared early in seven patients, occurred remote from infarction in seven others and showed a progressive pattern in six.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335691 TI - Cineangiographic spectrum of Ebstein's malformation: its relevance to clinical presentation and outcome. AB - Eight heart specimens were examined that had concordant connections of the cardiac segments and exhibited Ebstein's malformation. The displacement of the leaflets of the tricuspid valve from the atrioventricular junction varied from minimal and isolated involvement of the septal leaflet to involvement of the mural and anterosuperior leaflets as well. This resulted in a wide range of physiologic "atrialization" of the right ventricle. The distal insertion of the valve leaflets also exhibited a spectrum of malformation. At one end the insertion was the normal focal variety, allowing free communication between the atrialized and functional parts of the right ventricle. At the other end there was abnormal linear attachment of the anterosuperior and mural leaflets to an anomalous muscular shelf at the junction between the inlet and apical trabecular portions of the right ventricle. The anteromedial commissure between the anterosuperior and the displaced septal leaflets provided a "keyhole" communication between the two ventricular compartments. Between these extremes were cases in which hyphenations along a locus of linear attachment allowed additional communications between the ventricular compartments. In light of these anatomic observations, cineangiograms of 26 patients with Ebstein's malformation were reviewed retrospectively. It was possible to classify the patients into three groups with focal, hyphenated and linear attachment, respectively. Size, ejection and displacement indexes of the functional right ventricle measured from the angiograms suggested that the severity of the malformation increased from focal attachment through hyphenated to linear attachment. Clinical observations relative to symptoms (cyanosis at rest, reduced exercise tolerance) and outcome supported this morphologic-angiographic grading. PMID- 3335690 TI - Arrhythmia and prognosis in infants, children and adolescents with hypertrophic cardiomyopathy. AB - In adults with hypertrophic cardiomyopathy, the annual mortality rate from sudden death is 2 to 3%, and the finding of nonsustained ventricular tachycardia during electrocardiographic (ECG) monitoring provides a marker of the patient who is at increased risk. In the young, the annual mortality rate from sudden death is even higher, approximately 6%, but the prognostic significance of arrhythmia is unknown. To determine the prevalence of arrhythmia and its relation to prognosis, 2 days of ECG monitoring was performed in 6 infants, 14 children and 33 adolescents with hypertrophic cardiomyopathy receiving no cardioactive medications. An additional 1 to 9 days (median 2) of monitoring was performed in 29 patients. All patients had sinus rhythm; 4 adolescents had episodes of paroxysmal supraventricular tachycardia, a child with the Wolff-Parkinson-White syndrome had symptomatic reentrant atrioventricular tachycardia and 5 adolescents had asymptomatic nonsustained ventricular tachycardia. During follow-up of 1 week to 7 years (median 3 years), five patients died suddenly and two had successful resuscitation from out-of-hospital ventricular fibrillation; none of these seven patients had ventricular arrhythmias during 2 to 7 days (median 3) of ECG monitoring. The two patients with ventricular fibrillation, the five with ventricular tachycardia, the one with Wolff-Parkinson-White syndrome and the seven with recurrent syncope or adverse family history, or both, received low dose amiodarone. None of these "high risk" patients died during 6 months to 6 years (median 3 years) of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335692 TI - Conduction disturbances after correction of tetralogy of Fallot: are electrophysiologic studies of prognostic value? AB - Late complete heart block may occur after correction of tetralogy of Fallot. Whether postoperative electrophysiologic studies can identify patients at risk of developing this conduction disturbance is unknown. In this study, 57 children who underwent electrophysiologic investigation after correction of tetralogy of Fallot were followed up for 1 to 13 (mean 6.5) years after the investigation. One late death and two cases of late complete heart block occurred. The late death was due to ventricular arrhythmia and not to a conduction disturbance. The cases of late heart block occurred 2 and 5 years, respectively, after electrophysiologic study, and in both cases the patient had a prolonged HV interval; in one patient progressive lengthening of the HV interval could be demonstrated at two subsequent studies 1 year apart. Another five patients with a prolonged HV interval had normally conducted sinus rhythm up to 11 years after study. Atrial pacing at increasing rates (up to the occurrence of second degree atrioventricular block) during electrophysiologic study was the best means of predicting late heart block: of three patients with block below the bundle of His occurring at pacing rates less than 180/min, two developed late complete heart block. Thus, electrophysiologic testing of the conduction system after correction of tetralogy of Fallot is useful in predicting late complete heart block and should be performed in patients with a history of transient heart block after surgery and in those with a prolonged PR interval. PMID- 3335693 TI - Evaluation of pulmonary blood supply by nuclear magnetic resonance imaging in patients with pulmonary atresia. AB - Nuclear magnetic resonance (NMR) imaging defines the blood pool without the need for contrast medium. Consequently, it may be useful for defining the pulmonary circulation in patients with pulmonary atresia, in whom opacification of these vessels can be problematic. Ten patients with pulmonary atresia were evaluated by gated NMR imaging. The morphology of the right ventricular outflow tract, the size and the course of the central pulmonary vessels and the source of the collateral supply to the lung were assessed. Central pulmonary arteries were identified and measured in 9 of the 10 patients. One patient had no detectable central pulmonary arteries. Angiography confirmed the NMR findings in all but two patients, in whom NMR scanning visualized a main pulmonary artery that was not seen on angiography. Collateral arteries arising from the aorta or the arch vessels, as well as intracardiac malformations and aortic arch anomalies, were identified in all 10 patients. In six patients with palliative surgery, NMR imaging correctly demonstrated all patent shunts. Nuclear magnetic resonance imaging appears to be an effective noninvasive technique for evaluating patients with pulmonary atresia. However, tomographic thickness and spatial resolution are still limiting factors for this technique in infants. PMID- 3335694 TI - Disproportionate epicardial dilation after transmural infarction of the canine left ventricle: acute and chronic differences. AB - The relation between acute disproportionate infarct dilation and late postinfarct left ventricular remodeling was examined by implanting multiple radiopaque epicardial markers in the left ventricle of eight dogs and determining regional surface deformation after acute and chronic transmural infarction. Transmural injury was produced by combining coronary ligation with distal embolization of a rubber polymer. Dogs were anesthetized and studied before and 1 h, 24 h and 1 week after infarction. Marker positions were recorded by rapid biplane cineradiography, and three-dimensional coordinates were reconstructed by a computer-assisted tracking system. Regional deformation was expressed by a local surface area equal to the sum of multiple (three to four) triangles generated by marker triplets. As early as 1 h after infarction, end-diastolic area in the infarct region increased by 20.3 +/- 3.1%, while that in the remote region increased by only 7.9 +/- 3.5%. Both changes and the difference between them were significant. At 24 h after infarction, both territories continued to undergo dilation, this time to a similar extent (additional +10.3% in the remote region and +10.1% in the infarct region), thus maintaining the significant disproportionate infarct dilation. At 1 week, however, the infarct territory remained dilated with a mean end-diastolic area 31.4 +/- 3.1% above control, while that in the remote region returned to a net mean 8.5 +/- 4.7% increase. Thus, the major extent of disproportionate infarct dilation occurs within 1 h after transmural injury and is accompanied by remote dilation as a compensatory response. The extent of further infarct dilation achieved by 24 h is maintained in the chronic infarct, and compensatory mechanisms enable noninjured myocardium to become less dilated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335695 TI - Disproportionate dilation after transmural infarction--reflections on its meaning. PMID- 3335696 TI - Endothelium determines flow-dependent dilation of the epicardial coronary artery in dogs. AB - The mechanisms of epicardial coronary artery dilation after reactive hyperemia were studied in instrumented conscious dogs. A pair of ultrasonic crystals, an electromagnetic flow probe and a cuff occluder were placed on the left circumflex coronary artery in 12 mongrel dogs under sterile conditions. Reactive hyperemia after 20 s of coronary occlusion dilated the epicardial coronary artery by 120 +/ 14 micron (3.8 +/- 0.6%, p less than 0.01) from 3.167 +/- 0.345 mm. This reactive dilation was abolished by flow-limiting coronary stenosis. However, vasodilation after nitroglycerin was 168 +/- 26 micron (5.1 +/- 0.5%) and 162 +/- 27 micron (4.9 +/- 0.6%), respectively, before and after flow limitation. After removal of the endothelium by a balloon catheter, dilation of the epicardial coronary artery after reactive hyperemia was markedly attenuated to 7 +/- 4 micron (p less than 0.01 versus before denudation), despite the presence of a similar degree of reactive hyperemia. The extent of coronary dilation after nitroglycerin was unchanged before and after de-endothelialization. Thus, the endothelium contributed to reactive dilation but not to the nitroglycerin-induced dilation. The negative feedback control of coronary diameter to changes in flow velocity may relate to the regulation of coronary artery tone. PMID- 3335697 TI - Acute reduction in functional infarct expansion with late coronary reperfusion: assessment with quantitative two-dimensional echocardiography. AB - Reperfusion performed too late to salvage myocardium decreases chronic infarct expansion in experimental animals. However, the acute effects of delayed reperfusion are not known. Twenty-two dogs underwent 3 (n = 8), 4 (n = 8) or 6 h (n = 6) of circumflex artery occlusion followed by 3 h of reperfusion. Effects of reperfusion on diastolic expansion were assessed in two ways: 1) change in mean radius of curvature of the infarct segment, and 2) change in the ratio of the length of the diameter from the center of the infarct zone to the opposite wall (septal-lateral diameter) to the length of the diameter perpendicular to this (anteroposterior diameter). Effects on systolic expansion were examined with quantitative two-dimensional echocardiographic systolic thickening analysis. Delayed reperfusion produced an immediate decrease in diastolic infarct expansion. The ratio of septal-lateral/anteroposterior diameters, which had increased with occlusion from a preocclusion baseline of 0.98 +/- 0.06 to 1.13 +/ 0.08 (p less than 0.001), decreased with reperfusion to 1.02 +/- 0.07 at 15 min and 1.03 +/- 0.08 at 3 h of reperfusion (p = 0.001). This was due solely to a decrease in the septal-lateral diameter. The radius of curvature of the infarcted segment increased from 2.1 +/- 0.5 cm before reperfusion to 2.74 +/- 0.8 cm at 15 min and 2.6 +/- 0.85 cm at 3 h of reperfusion (p = 0.009). This occurred despite a significant (13.6%) decline in end-diastolic cavity area and is compatible with flattening of the reperfused infarct region. Systolic infarct expansion also improved slightly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335698 TI - Importance of clinical measures of ischemia in the prognosis of patients with documented coronary artery disease. AB - To examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutive patients who had symptomatic significant (greater than or equal to 75% stenosis) coronary artery disease were studied. Using the Cox regression model in a randomly selected half of the patients, the prognostically independent clinical variables were weighted and arranged into a simple angina score: angina score = angina course X (1 + daily angina frequency) + ST-T changes, where angina course was equal to 3 if unstable or variant angina was present, 2 if the patient's angina was progressive with nocturnal episodes, 1 if it was progressive without nocturnal symptoms and 0 if it was stable; 6 points were added for the presence of "ischemic" ST-T changes. This angina score was then validated in an independent patient sample. The score was a more powerful predictor of prognosis than was any individual anginal descriptor. Furthermore, the angina score added significant independent prognostic information to the patient's age, sex, coronary anatomy and left ventricular function. Patients with three vessel disease and a normal ventricle (n = 1,233) had a 2 year infarction-free survival rate of 90% with an angina score of 0 and a 68% survival rate with an angina score greater than or equal to 9. With an ejection fraction less than 50% and three vessel disease (n = 1,116), the corresponding infarction-free survival figures were 76 and 56%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335699 TI - Sensitivity of isovolumic relaxation to hypothermia during myocardial infarction. AB - Effects of moderate spontaneous hypothermia on left ventricular systolic and diastolic function during acute myocardial infarction were documented in 17 anesthetized dogs with micromanometric pressure and ventriculographic dimension recordings acquired at baseline and at 1 and 3 h after coronary occlusion. In Group 1 (n = 5), core temperature was allowed to decline spontaneously. In Groups 2 (n = 6) and 3 (n = 6), core temperature was maintained at normothermic levels. Hypothermia impaired isovolumic relaxation markedly despite its lack of effect on ventricular volumes or ejection fraction. At 32.3 degrees C, tau 1/2, defined as the time needed for the left ventricular pressure at the time of peak negative rate of change of left ventricular pressure (dP/dt) to fall by 50%, was increased by 129% 3 h after occlusion. In addition, at this temperature significant changes were found in heart rate, cardiac output, minute work, peak positive and peak negative dP/dt, systolic ejection time, mean velocity of circumferential fiber shortening, mean aortic pressure and end-diastolic pressure. Thus, hypothermia evolving under conditions of general anesthesia profoundly alters left ventricular function in the setting of acute myocardial infarction, a phenomenon that requires consideration and control in studies of myocardial ischemia and left ventricular function in experimental animals. PMID- 3335700 TI - Amiodarone and desethylamiodarone: plasma concentrations, therapeutic effects and side effects. PMID- 3335701 TI - The patient with angina: the importance of careful listening. PMID- 3335702 TI - Noninvasive identification of severe coronary artery disease using exercise radionuclide angiography. AB - The ability of exercise radionuclide angiography to predict the risk of having significant left main or three vessel coronary artery disease was examined in 681 patients who underwent both radionuclide and coronary angiography. There were significant differences in multiple variables between patients with or without such disease. Logistic regression analysis identified seven variables as independently predictive of the presence of left main or three vessel disease. Using these variables, low, intermediate and high probability groups could be identified. The four most important variables--the magnitude of exercise ST segment depression, peak exercise ejection fraction, peak exercise rate-pressure product and sex of the patient--can provide practical estimates of the risk of having left main or three vessel disease. Exercise radionuclide angiography can provide a clinically useful noninvasive estimate of the risk of having significant left main or three vessel disease. PMID- 3335703 TI - Prognostic value of the simplified Selvester QRS score in patients with coronary artery disease. AB - The relation of the simplified Selvester QRS scoring system for the estimation of myocardial infarct size to survival was studied in 1,915 nonsurgically treated patients with documented coronary artery disease. Electrocardiograms (ECGs) were scored according to a simplified 29 point QRS scoring system. Using Cox model analyses, QRS scores were found to provide strong prognostic information by themselves (p less than 0.0001). Higher QRS scores were associated with lower survival rates. Patients with a score of 0 had a 1 year survival rate of 95% and a 5 year survival rate of 88%; patients with a score of 10 or more had survival rates of 81 and 52%, respectively, at the same intervals. Directly compared with the presence or absence of Q waves on the ECG, QRS scores provided greater prognostic information (p less than 0.001). When compared with 13 individual factors previously shown to provide the greatest independent prognostic information, the QRS score was the third most powerful individual prognostic factor. It did not contribute independent prognostic information in combination with the whole group, but did provide independent information in combination with the six most predictive factors. Its prognostic information overlapped mostly with clinical factors related to heart failure, and combined best with clinical factors related to the severity of ongoing myocardial ischemia. Because it is inexpensive and simple and maximizes the prognostic information from the ECG, the simplified Selvester QRS scoring system can be a useful clinical descriptor for practitioners and clinical investigators. PMID- 3335705 TI - Prolapse paranoia. PMID- 3335704 TI - Long-term follow-up of idiopathic mitral valve prolapse in 300 patients: a prospective study. AB - A prospective long-term follow-up study was made of 300 patients with idiopathic mitral valve prolapse, diagnosed by clinical, cineangiographic and echocardiographic criteria. There were 136 male and 164 female patients, ranging in age from 10 to 87 years (mean 42.2). The study included all patients with primary mitral valve prolapse, irrespective of clinical condition at the onset, and excluded only those patients with "secondary" mitral valve prolapse attributable to an accompanying established disorder. The average follow-up period was 6.1 years (range 6 months to 20 years). Two patients died of a noncardiac cause. The clinical condition of 153 patients remained stable. In 27 patients a supraventricular tachycardia occurred that was readily controlled with medication and caused no serious clinical complications. In 20 patients signs of mitral regurgitation appeared, but the patients remained clinically asymptomatic. Serious complications developed in 100 patients. Sudden death, most likely due to ventricular fibrillation, occurred in three patients; documented ventricular fibrillation was seen in two. Ventricular tachycardia developed in 56 patients, but in all instances the rhythm disorder was managed effectively and durably with medication. Infective endocarditis occurred in 18 patients, 4 of whom died during treatment and 6 of whom needed mitral valve replacement. The remaining eight patients suffer from severe mitral regurgitation that will require surgery in the near future. Twenty-eight patients underwent mitral valve operation because of progressive regurgitation. Cerebrovascular accidents occurred in 11 patients, but lifelong treatment with coumarin derivatives or antiplatelet aggregation agents was not considered necessary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335706 TI - Effects of aging on asynchronous left ventricular regional function and global ventricular filling in normal human subjects. AB - In many patients with coronary artery disease or hypertrophic cardiomyopathy, reduced left ventricular rapid diastolic filling is related to asynchronous left ventricular regional diastolic function. Because left ventricular filling also declines with aging in normal subjects, in this study the influence of regional ventricular diastolic asynchrony on global ventricular filling as a function of age was investigated in 66 normal volunteers aged 19 to 77 years (mean 42) by radionuclide angiography. No subject had systemic hypertension or left ventricular hypertrophy. Indexes of left ventricular systolic function at rest did not vary with age, but rapid diastolic filling significantly declined with age: peak filling rate decreased (r = 0.69), time to peak filling rate increased (r = 0.53) and magnitude of rapid filling (% of left ventricular end-diastolic volume) decreased (r = 0.76) with aging. Left ventricular synchrony was assessed from regional volume curves derived by dividing the global ventricular region of interest into four quadrants. Indexes of systolic synchrony were unaffected by age, but regional variation in time to peak filling rate, an index of diastolic asynchrony, increased with aging (r = 0.51, p less than 0.001). Moreover, variation in time to peak filling rate correlated with global peak filling rate and magnitude of rapid filling (r = 0.48 and 0.54, p less than 0.001 for both). Multivariate analysis indicated that these effects were independent of age related changes in blood pressure. Thus, aging alters left ventricular diastolic function, with reduced rate and extent of the rapid filling phase related to increased regional diastolic asynchrony.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335707 TI - Contrast echocardiography during coronary arteriography in humans: perfusion and anatomic studies. AB - In humans, the physiologic relation between myocardial blood flow and epicardial coronary artery anatomy remains poorly defined. With the recent development of sonicated microbubble contrast agents, it is now possible to use contrast echocardiography to assess myocardial perfusion and to correlate blood flow with angiographically identified coronary artery anatomy. The purpose of the current study was to determine myocardial perfusion patterns in patients without significant coronary artery disease. The results may be used as a reference to analyze myocardial blood flow in patients with coronary artery disease. Sonicated meglumine sodium diatrizoate solution (Renografin-76), which contains microbubbles measuring 4.5 +/- 2.8 micrograms in diameter by laser analysis, was used as the echocardiographic contrast agent during elective coronary arterriography in 14 patients without significant coronary artery disease. Patients received intracoronary injections of 1.5 to 2 ml of sonicated Renografin 76 without complications. Perfusion characteristics were studied by visual assessment of the two-dimensional echocardiographic images obtained after individual injections. In patients found to be free of significant coronary artery disease by arteriography, the left coronary system always supplied the anteroseptal, anterior, anterolateral and posterior regions of the left ventricle at the mid-papillary, cross-sectional level. The right coronary artery system perfused the inferior and inferoseptal regions in 89% of the patients identified with a right dominant system. The anterolateral papillary muscle was perfused from the left coronary system in all cases. The posteromedial papillary muscle was perfused from the left coronary system in 58% of the patients and from the right system in 42% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335708 TI - Noninvasive evaluation of aortic stenosis severity utilizing Doppler ultrasound and electrical bioimpedance. AB - Aortic valve area was calculated noninvasively in 30 patients with aortic stenosis undergoing cardiac catheterization. Continuous wave Doppler ultrasound was employed to estimate the mean transvalvular pressure gradient. The mean left ventricular outflow tract flow velocity and cross-sectional area were determined from pulsed Doppler and two-dimensional ultrasound recordings. Electrical transthoracic bioimpedance cardiography performed simultaneously with the ultrasonic study and repeated at the time of catheterization measured heart rate, systolic ejection period and cardiac output. These noninvasive data permitted calculation of aortic valve area using the Gorlin equation (range 0.21 to 1.75 cm2) and the continuity equation (range 0.25 to 1.9 cm2). Subsequent cardiac catheterization showed valve area to range from 0.21 to 1.75 cm2. The mean Doppler pressure gradient estimate was highly predictive of the gradient measured at catheterization (r = +0.92, SEE = 10). Bioimpedance cardiac output measurements agreed with the average of Fick and indicator dye estimates (r = +0.90, SEE = 0.52). Valve area estimates utilizing continuous wave Doppler ultrasound and electrical bioimpedance were superior (r = +0.91, SEE = 0.12) to estimates obtained utilizing the continuity equation (r = +0.76, SEE = 0.29) and were more reliable in the detection of patients with severe aortic stenosis (9 of 11 versus 6 of 11). These data show that 1) electrical bioimpedance methods accurately estimate cardiac output in the presence of aortic stenosis; 2) the hybridized bioimpedance-Doppler ultrasound method yields accurate estimates of aortic stenosis area; and 3) the speed, accuracy and cost-effectiveness of aortic stenosis evaluation may be improved by this hybridized approach. PMID- 3335709 TI - Diastolic mitral and tricuspid regurgitation by Doppler echocardiography in patients with atrioventricular block: new insight into the mechanism of atrioventricular valve closure. AB - The purpose of this study was to prospectively determine the incidence of diastolic mitral and tricuspid regurgitation in atrioventricular (AV) block using Doppler echocardiography. The temporal relation between mitral and tricuspid diastolic insufficiency and the diastolic murmur recorded in patients with complete heart block was also investigated. Twenty-two consecutive patients with AV block (referred to the Echo-Doppler laboratory for routine clinical studies), aged 18 to 87 years, were enrolled in the study. Eleven patients had third degree AV block and a ventricular-inhibited (VVI) pacemaker, two patients had second degree AV block, seven patients had first degree AV block, one patient had blocked premature atrial complexes and one patient had atrial flutter with 4:1 AV block. Diastolic mitral regurgitation was detected in 20 patients, and diastolic tricuspid regurgitation in 21. A mid-diastolic murmur was detected in all patients except in the three youngest. The murmur occurred before diastolic regurgitation and coincided with peak forward flow through the AV valve after atrial contraction. M-mode mitral valve echocardiograms obtained in nine patients demonstrated near closure of some portions of the mitral valve after atrial contraction. Effective closure of the valve, however, did not occur unless ventricular systole supervened. In conclusion, diastolic mitral and tricuspid regurgitation are almost universally present in patients with AV block and are associated with a diastolic murmur. The murmur coincides with forward AV valve flow. Diastolic regurgitation is silent. Effective AV valve closure is not established until ventricular systole occurs, as demonstrated by M-mode echocardiographic recording of the mitral valve. PMID- 3335711 TI - Ethical issues in nutrition care. PMID- 3335710 TI - Physiologic correlates of the heart rate response to upright isotonic exercise: relevance to rate-responsive pacemakers. AB - Rate-responsive cardiac pacing requires a sensitive physiologic variable that is closely correlated with the heart rate-oxygen uptake relation, particularly in patients with heart failure whose cardiac output response to exercise is more dependent on heart rate. Accordingly, the heart rate response to upright exercise was measured in 81 patients with heart failure or hypertension, or both, and in 27 normal subjects. Oxygen uptake (VO2), minute ventilation (VE), cardiac output, right heart pressures and the mixed venous temperature, oxygen saturation (SvO2) and pH were analyzed throughout exercise. Linear regression analysis of these variables with heart rate revealed the following: 1) There was a highly linear heart rate-VO2 relation in each subject (the average slope of this relation was greater [p less than 0.05] in patients with more severe failure). 2) VE was highly correlated with exercise heart rate, and its slope was not different between normal subjects and patients. 3) Mixed venous temperature and pH were poor predictors of exercise heart rate, particularly at low or moderate levels of work; however, SvO2 was highly correlated with heart rate for all levels of work. Thus, in normal subjects and patients with heart failure or hypertension, or both, heart rate increases linearly with isotonic leg exercise. Minute ventilation and mixed venous oxygen saturation are highly correlated with this response and may serve as potential sensors for rate-responsive pacemakers. PMID- 3335712 TI - The effects of diet and life-style on bone mass in women. AB - Osteoporosis is characterized by a reduction in bone density. The majority of Caucasian women are at risk for osteoporosis-related fractures, especially in the wrist, spine, and hip. The degree of fracture risk at a specific bone site is best assessed by measuring the density of the bone with single- and dual-photon absorptiometry or with computed tomography. Bone density in women at any adult age is quite variable. Numerous diet and life-style factors are thought to influence bone density and, in turn, fracture risk. Strong evidence exists for a relationship between bone density and amenorrhea, body weight, alcoholism, smoking, and inactivity. In contrast, conflicting or insufficient evidence exists for a relationship with dietary protein, phosphorus, caffeine, and calcium intake. To minimize fracture risk, young women should have regular menses, consume a nutritionally adequate diet, perform regular physical activity, and, probably, use fluoridated water. When immediately postmenopausal, women should seriously consider estrogen replacement, since osteopenia is the rule, rather than the exception, in old age. PMID- 3335714 TI - Consulting dietitians in nursing homes: time in role functions and perceived problems. AB - A mail survey was conducted to describe Illinois consultant dietitians' perceptions of time adequacy for fulfilling role responsibilities and to identify dietary problems in nursing homes. Approximately three-fourths (74%) of the 43 respondents reported insufficient time at nursing homes, although all met or exceeded state consulting time requirements. Role functions receiving the greatest time investments were in the categories of foodservice management and nutrition care. Resident nutrition care issues were often rated as major problems. Dietitians' perceptions of nutrition care problems and inadequacy of time to perform role functions indicate a need to re-evaluate priorities for role performance and to obtain increased service hours. Methods to increase consulting time should include effective marketing of services and involvement in legislative and regulatory processes. PMID- 3335713 TI - The effectiveness of a short curriculum unit in death education for dietetic students. AB - Dietetic educators are concerned with preparing their students to interact effectively with seriously/terminally ill patients in clinical settings. In this study, a short death education curriculum unit including multi-media teaching materials was designed, implemented, and evaluated. The subjects were 47 junior students enrolled in three coordinated programs. Instruments were adopted or adapted to assess the following items: knowledge of the grief process, personality traits of empathy and dogmatism, fear of death, fear of interacting with the dying, attitudes toward working with terminally ill clients as part of the professional role of dietitians, and clinical performance. Scores for the traits of empathy and dogmatism were negatively related, and students with a higher degree of religious conviction had lower death fear scores. Although no significant changes were found in any of the attitude scores after the curriculum unit, most students indicated that the unit made them feel more comfortable about working with the seriously ill. Students and faculty recommended that death education be included for dietetic students. PMID- 3335715 TI - Documentation of time expenditures of clinical dietitians: results of a statewide time study in Texas. AB - The purpose of this study was to establish a profile of the amount of time expended by clinical dietitians in providing nutrition services. One hundred twenty-seven dietitians in 49 hospitals in Texas collected time data according to nutrition care activity, diet order classification, care level, and diagnosis. Frequency, mean time, standard deviation, and percentage of time were computed for each of the variables. Data were analyzed to ascertain relationships among the variables. The dietitians expended 50.7% of their time performing client related activities, 9.8% in administrative/managerial functions, 1.0% in professional activities, 5.1% in non-professional activities, 14.0% in delay activities, and 19.5% in transit time. The diet order classification that required the largest amount of the dietitians' time according to selected components of the nutrition care process was the calorie-controlled diabetic diet. Among the four nutrition care levels, dietitians expended the greatest percentages of time providing services for patients requiring intermediate (35.4%) and advanced intermediate care (30.4%). Dietitians expended more time providing client-related activities to patients diagnosed with diseases and disorders of the endocrine and excretory systems than to other patients. Mean times provide the clinical manager with documentation for determining staffing needs and costs of services. PMID- 3335716 TI - Weight-control approaches: a review by the California Dietetic Association. AB - Weight reduction is considered a therapeutic success if weight loss is maintained with no expense to overall health. The California Dietetic Association, a professional organization including 5,000 registered dietitians, proposes, on the basis of a review of the current scientific literature, the following criteria for health-safety evaluation of dietary approaches. A weight-reduction diet should (a) satisfy all nutrient needs except energy, (b) meet individual tastes and habits, (c) minimize hunger and fatigue, (d) be readily obtainable and socially acceptable, (e) favor the establishment of a changed eating pattern, and (f) be conducive to improvement of overall health. Characteristics of diet approaches associated with poor outcome include (a) very-low-calorie diets, which promote rapid weight loss, (b) extremes of macronutrient restriction, and (c) reliance on formula diets or special products. The use of diets, surgery, drugs, exercise, and behavior modification is discussed. PMID- 3335717 TI - Anorexia nervosa: psychological considerations for nutrition counseling. AB - This article presents the underlying psychological beliefs and self-perceptions held by individuals with anorexia nervosa. The intent of this article is to help dietitians and other nutrition counselors become more aware of the psychological characteristics of individuals with anorexia nervosa and become familiar with various counseling skills that can assist counselors when they are working toward reaching the goal of re-establishing normal eating patterns and attitudes about food. Counseling approaches that may be used by the nutrition counselor in an effort to deal effectively with the various psychological characteristics displayed by anorexics are provided. Nutrition counselors must be well informed of the psychodynamic aspects that prevail in the disorder, such as low self esteem, frustration over gaining weight, and a distorted body image. In addition, nutrition counselors must be aware of the particular communication skills (e.g., attentive listening, empathic responses, and verbal encouragement) and basic therapeutic methods (e.g., encouraging self decision making and providing support and acceptance of thoughts, feelings, and actions) that can be used for effecting positive growth and changes in dietary behavior of individuals with anorexia. PMID- 3335718 TI - Task force: a management technique that produces quality decisions and employee commitment. AB - A task force is a technique that can be used by the dietitian-manager to develop solutions for specific, identified problems. Because employees are directly involved in the decision-making process, better solutions--ones that are also more acceptable to the work group--result. To implement a task force, management must plan the strategy: Select a facilitator, explain the concept and problem to the work group, select task force participants, and make meeting arrangements. The task force meetings should be structured to maximize efficiency and productivity. The plan of action is developed by the task force members; all decisions are based upon input from the work group. Successful implementation of the solutions is the responsibility of the task force. Applications for task forces in both the clinical and food management areas are numerous and result in both tangible and intangible benefits. PMID- 3335719 TI - Home-delivered meals: food quality, nutrient content, and characteristics of recipients. AB - Meals provided by a home-delivered meal program with the same supplier were evaluated for 5 consecutive days in each of 6 years. In the evaluations, meals were compared with federal guidelines for meal pattern, serving size, and temperature of hot food, and the quality was evaluated. Meal pattern and serving size guidelines were not always met by the meals. Problems included no delivery of milk with the meals and variations in serving sizes for meat or alternate, fruit, vegetable, and dessert. Temperatures of hot foods were often much lower than the 140 degrees or 150 degrees F specified in food safety guidelines. Food quality varied. Protein, iron, phosphorus, vitamin A, and niacin were consistently greater than 33% of the RDA; energy, thiamin, riboflavin, and vitamin C were less than 33% of the RDA some years, and calcium was consistently less than 33% of the RDA. Estimated total daily nutrient intakes of 27 recipients followed the same pattern as the nutrient content of the meals. For many recipients, estimated nutrient intakes from food other than the home-delivered meal was less than 33% of the RDA. Food preferences were fairly well satisfied. Recall of nutrition-related vocabulary was poor. In this study, home-delivered meals were found to make important contributions to the nutrition needs of the recipients. PMID- 3335720 TI - Comparing effects of two types of weight-control counseling on motivation and weight loss. PMID- 3335721 TI - Expediting medical record charting by use of adhesive labels. AB - The use of adhesive labels in nutrition care charting has increased the documentation of registered dietitians and dietetic technicians in the medical record of each patient. At least to some extent, this improvement can be attributed to adhesive labels overcoming several "roadblocks" to charting. Credit for improvement must also be attributed to increased emphasis placed on charting throughout the dietetics profession. Increased charting has contributed to a more prominent role for the registered dietitian and dietetic technician in the daily care of the patient. Emphasis must continue on the quality of charting. Goals include reports that have a professional appearance and are concise yet contain pertinent details for patient care and reimbursement. PMID- 3335722 TI - Improved food intake and weight gain in adult patients following electroconvulsive therapy for depression. AB - Six elderly patients were referred for nutrition assessment and treatment because of poor dietary intake and weight loss associated with a major depressive illness. The patients underwent electroconvulsive therapy (ECT) administered by their psychiatrists approximately 3 times per week. During ECT, all patients increased their caloric intake (280 +/- 180 to 1,510 +/- 60 kcal/day, mean +/- SEM) to exceed their basal energy expenditure; major improvements in their depressive symptoms and weight gain were seen in five of the six patients. Increased caloric intake seen with ECT may be an early, clinical criterion for identifying the effectiveness of antidepressant therapy when depression is associated with anorexia and reduced energy intake. PMID- 3335724 TI - Position of the American Dietetic Association: nutrition intervention in the treatment of anorexia nervosa and bulimia nervosa. PMID- 3335723 TI - Loss of vitamin C in vegetables during the foodservice cycle. PMID- 3335725 TI - Behavioral disturbance in dementia of the Alzheimer's type. AB - Behavioral problems are thought to be pervasive and devastating to patients with dementia of the Alzheimer's type and their families. Despite this, little empirical data are available concerning the nature of such impairments, their rate of occurrence or their relationship to the disease process. This study investigated 127 patients with a primary diagnosis of dementia of the Alzheimer's type. Two methods of behavioral assessment were employed: a standardized dementia rating scale and a checklist of behavioral problems. Results indicated a) the overall number of problems significantly increased with increased cognitive impairment, b) the types of problems reported varied with cognitive severity, and c) behavioral problems were not significantly associated with patient's age, gender, duration, or age at onset of dementia. These findings are discussed as they relate to the phenomenology of dementia of the Alzheimer's type and to suggestions for interventions at different stages of the disease process. Problems found associated with level of impairment such as wandering, agitation, incontinence, and poor personal hygiene are thought to be characteristic of the disease and therefore predictable. Problems found not associated with level of impairment such as hallucinations, irrational suspicions, falls, and restlessness are likely to be idiosyncratic. The former should probably be incorporated into education and intervention programs; the latter addressed as needed on an individual basis. PMID- 3335726 TI - Unrecognized cognitive impairment in cardiac rehabilitation patients. AB - To determine the prevalence of unrecognized brain dysfunction accompanying chronic severe cardiac disease, we examined 20 clinically stable consecutive admissions to a cardiac rehabilitation service who were free of known stroke or dementia. Age range was 47 to 85 years (mean +/- SEM, 72.5 +/- 2.1 years), the male: female ratio was 10:10. Multiple cognitive deficits including significant memory impairment and disorientation were present in eight patients (40%), and seven of these eight patients were unable to administer their own medications reliably. An additional six patients (30%) showed milder impairments. One patient was found to be normal after neurological examination, four showed evidence of a single brain lesion, and 15 of 20 (75%) had multiple neurological abnormalities suggesting multifocal brain disease. The mechanism of cognitive deficits in cardiac patients is unclear, and it may be related to multiple infarcts, or acute or chronic hypoxic damage secondary to arrhythmias, cardiac failure, or small vessel disease of the brain. The term "circulatory dementia" is proposed to describe patients with vascular disease and non-Alzheimer type dementia. Patients with cardiac disease should undergo cognitive screening, as early identification of patients at risk of progressive intellectual loss may allow early use of preventive therapy. PMID- 3335727 TI - Acute effects of exercise on neuropsychological function in elderly subjects. AB - Fit elderly score higher on tests of fluid intelligence than aged-matched sedentary controls. Elderly patients who have taken part in exercise programs have shown improvement in mental function. We compared the effects of 45 minutes of exercise on memory, mood, and cognitive function in elderly subjects to a control intervention using a randomized control study design. Neuropsychological tests employed where the color slide test, digit symbol test, digit span test, logical memory test, word fluency test, and the Mini-Mental State Examination. We measured mood using a mood test and geriatric depression scale. Each subject was tested before, and immediately after, control and exercise sessions. Fifteen elderly subjects [ten men and five women; mean age, 66 years, (range, 60 to 85 years)] completed the study. There was a greater improvement in six of the eight scores of cognitive function following exercise, compared to control. These differences were significantly greater following exercise for the logical memory test score (P less than or equal to 0.02) and Mini-Mental State Examination (P less than or equal to 0.025) compared with the control intervention. PMID- 3335728 TI - Reduction of urinary incontinence in nursing homes: does it reduce or increase costs? AB - Labor and supply costs associated with the care of urinary incontinent patients in three nursing homes were measured. First, normal nursing home changing patterns and their associated costs were measured. Second, the costs were documented when patients were checked by research staff and changed on an hourly basis as needed. Nursing home staff changed patients significantly less frequently than patient voiding as detected by the hourly checking system. Thus, cost of incontinence during the hourly checking condition ($3.35) per 12-hour patient-day was significantly higher than the cost normally incurred in nursing homes ($1.52) per 12-hour patient-day. The cost of an incontinence rehabilitation program, which significantly reduced incontinence episodes, was contrasted to the cost of incontinence as measured under both of the previous conditions. The rehabilitation program produced significant labor and supply savings only when compared with the hourly checking and changing system. Maintaining patients in a more continent condition costs significantly more than the direct incontinence cost normally incurred by the nursing home. Quality of life and other second order benefits must be considered if continence rehabilitation is to be judged cost-effective. PMID- 3335730 TI - Hospital and medical care use by nursing home patients: the effect of patient care plans. AB - Although there has been increasing attention to the ethical and legal issues involved in the patient's right to have treatment or hospitalization withheld, there have been few empirical evaluations of programs designed to accomplish that end. Over a 7-year period, a medical group cared for 110 patients in a skilled nursing facility. After assessing the patients' wishes and the opinions of the personal physicians and nurses, care plans were made specifying whether each one was to receive maximum, intermediate, or comfort care. The hospitalization rate was found to be 79% lower for the patients receiving comfort care. Multiple admissions were unusual. Those patients made no use of outpatient consultants or major diagnostic procedures and had only 14% as many roentgenograms as the patients receiving maximum care. Whereas acute medical and surgical problems and related physician visits were more frequent for the comfort care groups, specific treatment of those problems was withheld far more often. Mortality was twice as great among the comfort care patients, and nearly all of these deaths occurred in the nursing home. It was concluded that the patient's decision to avoid active management can be honored by specific patient plans carefully communicated to all physicians sharing responsibility for that person's care. PMID- 3335729 TI - Habit training and oxybutynin for incontinence in nursing home patients: a placebo-controlled trial. AB - In order to determine if a bladder-relaxant drug could enhance the effectiveness of a toileting program for incontinence among functionally impaired nursing home patients, 15 patients with detrusor hyperreflexia were enrolled in a 6-week trial during which they were put on a habit training protocol alone for 2 weeks, habit training (HT) and a placebo for 2 weeks, and then HT and oxybutynin for 2 weeks (2.5 mg three times daily for 1 week, then 5 mg three times daily for 1 week). Bacteriuria, which was present without other symptoms in 11 of the 13 patients who completed the trial, was treated before HT began. Eradication of the bacteriuria resulted in a small, statistically significant increase in cystometric bladder capacity (44 mL; 95% confidence interval 16 to 72 mL), but the detrusor hyperreflexia and frequent episodes of incontinence persisted. HT alone reduced the mean percentage of every-two-hour checks which were wet from 43% to 32% (95% confidence interval of the difference -1% to -21%; P = .04 by a paired t test); addition of placebo and active drug did not result in any further reduction. Cystometric bladder capacity had not changed significantly by the end of the trial (measured while patients were still on active drug), and there was no consistent relationship between changes in bladder capacity and changes in wet checks. Although our sample size is small, the data are consistent with other studies in similar populations. The relatively practical and inexpensive interventions we employed in this study will need to be modified or intensified in order to substantially reduce the frequency of incontinence among functionally disabled nursing home patients. PMID- 3335731 TI - Erectile failure in the aged: evaluation and treatment. AB - With aging, there are changes in both libido and erectile function. Although the majority of aged men remain interested in sex, less than 15% report continued sexual intercourse. The cause of this "libido-potency gap" is due primarily to erectile failure. Penile erection is dependent upon a complex interaction of the autonomic nervous system, cardiovascular system, and local neurotransmitters such as acetylcholine and vasoactive intestinal polypeptide. Sexual stimulation causes augmented blood flow into the corpora cavernosa, and restricted outflow, resulting in penile rigidity. With aging, there is a decline in gonadal steroids, nerve conduction velocity, and vascular compliance, any of which could interfere with normal erections. When disease is superimposed on the normal changes of aging, erectile function is further impaired. Evaluation of an elderly male with impotence may consist of a detailed drug history and trial of alternate therapy, as in the case of adverse drug reactions. More often, evaluation entails hormonal assays, penile vascular assessment, neurologic assessment, and an evaluation of nocturnal erectile function. Based on the results of these assessments, appropriate treatment alternatives can be chosen. With the availability of multiple treatment options, patients and physicians can now choose from a range of noninvasive or invasive alternatives depending upon the etiology, associated disorders, and preference of the patient. PMID- 3335732 TI - Continued treatment of the fatally ill for the benefit of others. AB - This paper examines the moral and professional issues present in cases involving continued treatment of fatally ill patients in order to benefit a third party. It is argued that such treatment can be justified in some cases from a moral point of view. Practical considerations make such cases difficult to identify at times. It is also argued on the other hand that professional concerns should rule out the permissibility of continuing such treatment. Thus, even though it may be morally permissible at times to continue treatment, it is not good medical practice to do so. PMID- 3335733 TI - The psychiatric symptoms of Alzheimer's disease. AB - The authors used a semistructured interview administered to primary family caregivers to assess the prevalence and nature of psychiatric pathology in 175 well-diagnosed community-residing Alzheimer's disease patients. Symptoms that are indicative of depression in the cognitively intact were virtually ubiquitous in this demented population. A variety of psychotic features were also regularly reported. The implications of these findings for the recognition and treatment of reversible psychiatric impairment are discussed. PMID- 3335734 TI - A seventy-eight-year-old woman with fever, cough, joint pains, and hypercalcemia. PMID- 3335735 TI - The American Geriatrics Society statement on two-step PPD testing for nursing home patients on admission. PMID- 3335736 TI - A "risk" approach to adverse drug reactions. PMID- 3335737 TI - Excess disability in demented elderly outpatients. The rule of halves. PMID- 3335738 TI - Postprandial hypotension in the elderly. PMID- 3335739 TI - Osteopenia in the elderly male. PMID- 3335740 TI - Vitamin B12 deficiency in demented patients. PMID- 3335741 TI - The importance of basic biological science to gerontology. PMID- 3335743 TI - A longitudinal study of energy expenditure in males during steady-state exercise. AB - Our purpose was to investigate longitudinal changes in gross energy expenditure (GEE) of 20 middle-aged and older men during submaximal exercise in 1969 and in 1985. GEE (kcal/min) was estimated using the caloric equivalent for each liter of oxygen consumed at the measured respiratory exchange ratio during submaximal exercise. The men performed a 10-min submaximal cycle ergometer exercise test at a power output (PO) of 100 W. Pedalling frequency was 50 rpm. Results showed a significant 5.9% decrease in GEE (p less than .01) from 8.5 +/- 0.8 (M +/- SD) kcal/min in 1969 to 8.0 +/- 0.4 (M +/- SD) Kcal/min in 1985. In addition, the effects of chronological age and leisure time physical activity on GEE were assessed and found to be nonsignificant, although a significant decrease in GEE over time (p less than .02) was observed in both groups. The present results support a decrease in GEE in middle-aged and older men over the 16-year time period. Furthermore, this decrease in GEE persisted regardless of chronological age or leisure time physical activity status. PMID- 3335742 TI - Influence of the restriction of individual dietary components on longevity and age-related disease of Fischer rats: the fat component and the mineral component. AB - The influence of restricting either the fat or the mineral component of the diet to the same extent as they are restricted in the life-prolonging, food restriction paradigm but without restricting calories was studied in regard to longevity and age-related pathologic lesions of barrier-maintained male Fischer 344 rats. Neither the restriction of fat nor the restriction of mineral influenced the median length of life or maximum life span as indicated by the age of the 10th percentile survivors. Restricting the dietary fat did retard the development of chronic nephropathy and associated lesions, but it also increased the prevalence of lymphoma and leukemia. The development of chronic nephropathy was not significantly affected by restricting the mineral component of the diet. PMID- 3335744 TI - Human taste bud density across adult age groups. AB - Some of the subjective variability attributed to taste experience could be related to wide variations of taste bud density. Studies of taste perception show a direct relationship between sensation and the number of receptors. Taste bud densities are quantified in this study using light microscopy to reconstruct two regions of 18 human cadaver tongues. Specimens came from male and female cadavers representing three age groups: young adults, middle-aged adults, and older adults. The results show a range of more than 100-fold in taste bud density that is evenly distributed among age groups and sexes. The disparity is not attributable to the state of health of the adults prior to death, and it is corroborated in the literature. Differences in taste bud density that extend across age groups probably confound some inferences about the effects of aging on taste sensitivity that are derived from cross-sectional studies of human populations. It is not clear from the data whether or not human taste bud density in individuals and in populations is stable or changing with time. PMID- 3335745 TI - Changes that occur and do not occur in the structure and function of skeletal muscle with aging. PMID- 3335747 TI - Sweating and cardiovascular responses of aged men to heat exposure. AB - In this study, 6 older and 10 younger Japanese men were exposed, while sitting, to 40 degrees C and 40% relative humidity for up to 130 min. All participants were heat unacclimatized. Physiological measurements included sweat responses, esophageal and skin temperatures, nonevaporative heat exchange, heart rate, cardiac output, blood pressure, forearm blood flow, and metabolic heat production. There was no significant difference in sweat rate or in onset of sweating between the older and younger men; however, esophageal temperature at the onset of sweating was greater in the older men. Changes in skin temperature, nonevaporative heat exchange, metabolic heat production, heart rate, and cardiac output were the same during heat exposure in both age groups. However, forearm blood flow before and after exposure to heat was significantly lower in the elderly group. These data suggest that the greater health risk posed to resting, yet healthy, aged men by hot environments is not a consequence of inadequate sweating but could be associated with retardation of the vasodilation reflex, which can prevent effective transfer of the body heat to its shell, thus resulting in greater heat storage. PMID- 3335748 TI - The effect of age on serum albumin in healthy males: report from the Normative Aging Study. AB - To clarify the relation between age and serum albumin, measures were obtained on a screened population of 1066 healthy males in the Normative Aging Study. Multiple regression analysis shows only a slight decline in albumin of 0.054 gm/dl per decade with R = -0.12 (p less than .001) on cross-sectional data. This small decline occurs entirely within the range of normal, contrary to many previous reports. Mean albumin values were 4.25 (+/- .26 SD) for subjects in the eighth decade and 4.13 (+/- .29 SD) in the ninth decade. Longitudinally, there was an upwards trend in albumin for five birth cohorts over an 8-yr period which may reflect laboratory drift. A multivariate model of cross-sectional data can explain only 5% of the variance. The age-related decline within healthy subjects is far less than previously described. Our data demonstrate that hypoalbuminemia is not a consequence of normal aging. PMID- 3335746 TI - The influence of dietary protein source on longevity and age-related disease processes of Fischer rats. AB - The influence of replacing dietary casein with soy protein on longevity and age related pathologic lesions of male Fischer 344 rats was investigated. Caloric intake and body weights were similar for rats on the two diets. Rats on the soy protein-containing diet had a median length of life of 844 days compared to 730 days for those on the casein-containing diet (p less than .002), and the ages of the 10th percentile survivors were 937 and 857 days, respectively (p less than .02). The progression of chronic nephropathy was markedly retarded by replacing casein with soy protein. Only 7% of the rats dying spontaneously on the soy protein-containing diet exhibited end-stage chronic nephropathy compared to 41% of the rats on the casein-containing diet. Clearly, the soy protein-containing diet enables ad libitum fed male Fischer 344 rats to be used as a model for aging research without the occurrence of renal failure as a major confounding problem. PMID- 3335749 TI - Spectral analysis of heart rate indicates reduced baroreceptor-related heart rate variability in elderly persons. AB - Spectral analysis of the cardiac interbeat interval was used to examine baroreceptor-related supine and standing heart rate variability (HRV) in young (less than 40 years of age) and elderly (greater than 60 years of age) healthy volunteers. Heart rates and blood pressures were examined also. When supine, average heart rate, systolic and diastolic blood pressure, and HRV for the young volunteers were 66.5 bpm, 113.0/64.3 mmHg, and 5.74 log units of relative power, respectively. The same values for the elderly group were 65.4 bpm, 126.3/74.0 mmHg, and 4.43 log units. Statistical analysis revealed that, compared to the young volunteers, supine elderly volunteers had similar heart rates, higher blood pressures, and lower baroreceptor HRV. There was little change in blood pressure in either group upon standing. However, upon standing, heart rate increased 17.7 bpm and baroreceptor HRV increased to 6.58 (+ 14.6%) in the younger volunteers. This was significantly different from the elderly volunteers, whose heart rate increased by only 10.9 bpm and their HRV to 4.72 (+ 6.5%). These results indicate that much of the reduction in HRV in old age results from decreases in baroreceptor modulation of heart rate. In addition, the difference between young and old persons is greatest in the standing position because elderly individuals exhibit less recruitment of baroreceptor activity with postural change. PMID- 3335750 TI - Health care implications of desire and expectancy for control in elderly adults. AB - Two cross-sectional studies explored the relationship between age and individuals' desire for control both on a general day-to-day level and as patients in health care situations. The relationship between age and expectancies for control over health also was examined. In Study 1, questionnaire surveys completed by 246 community adults ranging in age from 19 to 77 indicated that for health-specific measures at older ages, belief in internal control and desire for control are lower, and belief in control by powerful others is higher. In contrast, no significant differences in general desires for control were found across age groups. In Study 2, expectancies and desire for control in relation to the health of 350 patients about to undergo barium enemas, chemotherapy, or surgery were measured. Older adults reported a lower desire for control of their health care and a greater belief in the ability of powerful others to control their health than did younger adults. The replication of these age differences across samples differing in several respects, including education and health status, suggests that this is a highly reliable finding. PMID- 3335751 TI - The relationship between prior functioning on cognitive and personality dimensions and subject attrition in longitudinal research. AB - This study compared the intellectual and personality functioning of continuing participants in a longitudinal study with individuals who were lost from the panel after at least 7 years of involvement. Based on their reason for discontinuation, participants who were lost to the panel were categorized into three attrition groups: deceased, ill, and voluntary dropouts. When the performance of these groups prior to leaving the study was compared with that of the continuing participants, no general differences were found. However, specific differences were revealed, particularly on crystallized-type intellectual abilities and the personality factors. Participants who were lost due to illness or death had functioned at the lowest levels of the four groups prior to attrition. These effects varied by age. In late middle age, ill participants functioned at the lowest levels, whereas in old age, participants who subsequently died scored lowest of the four groups prior to attrition. Individuals who had voluntarily discontinued participation in the study most closely resembled the continuing participants, particularly in late middle age. The results indicate that performance effects associated with continued participation vary by age, the intelligence or personality factor being considered, and the reason for loss of the participant. Furthermore, they suggest that loss of participants from a longitudinal panel does not inevitably bias the validity of developmental findings. PMID- 3335752 TI - Age differences in bimanual coordination. AB - A bimanual coordination experiment was conducted in which two groups of 10 male and female participants, elderly (67 to 75 years of age) and young (21 to 25 years of age), produced unimanual, bimanual symmetrical (equal extent amplitude), and bimanual asymmetrical (unequal extent amplitude) movements. In addition to an overall increase in performance latency, the elderly group exhibited a linear increase in response initiation (RT) with increases in task complexity similar to that of the young group. However, the elderly participants showed a proportional increase over the young participants in response execution latency (MT). Further, the elderly group had a slower RT for short movements than long movements, an effect not found in the young group. Compared with the young participants, the elderly participants showed greater asynchrony in response initiation of bimanual movements; increased inability to subsequently compensate during response execution also resulted in a greater asynchrony in response termination. These results suggest specific aging deficits in bimanual coordination processes. PMID- 3335753 TI - The CES-D as a measure of depressive mood in the elderly Puerto Rican population. AB - The validity of the Center for Epidemiologic Studies Depression Scale (CES-D) was assessed using a sample of 60 elderly Puerto Ricans in New York City, half of whom were diagnosed clinically as depressed. The scale has high internal consistency reliability, discriminates strongly between patients and nonpatients, and relates in the expected fashion to theoretically relevant variables. There is some evidence that scores are influenced by socially desirable responding (SDR) and that these effects should be considered when examining the correlates of the CES-D in this population. Scale scores do not differ by interviewer. Overall, the CES-D appears to be a useful measure for studying within-group variability in depressive mood among older Puerto Ricans. PMID- 3335754 TI - Aging and free recall for objects located in space. AB - The free recall of objects located in space was examined in young and elderly respondents. The visual distinctiveness of the spatial context in which the stimulus objects were placed was varied systematically. Under conditions in which contextual cues were lacking (objects presented simply in a list format), or in which the context was visually bland (a two-dimensional, black-and-white map), the free-recall performance of elderly persons was significantly poorer than that of young adults. Under conditions in which visually distinctive cues were added to the spatial context (a colored map, a three-dimensional unpainted model, a three-dimensional painted model, or a large room), no difference in performance between young and elderly respondents was observed. Results support the hypothesis that visually distinctive cues produce greater depth of processing for elderly persons, facilitating free recall of objects located in space. PMID- 3335755 TI - Differences in the structure of Life Satisfaction Index in three generations of Mexican Americans. AB - This study examines differences in the structure of seven Life Satisfaction Index (LSI) items across three generations of Mexican Americans. Viewing the covariance structure of the items as a function of several parameter matrices, we analyzed factorial invariance by testing hypotheses involving equivalence constraints on one or more parameter matrices. Analysis of covariance structures, or LISREL, was used to assess the factorial invariance. Differences in the factorial structure of the LSI were found between the older generation and the other two generations (i.e., the middle-age and younger generations). These differences persisted even when generational differences in education, income, and acculturation were taken into account. Further analyses revealed that generational differences were contained in only one (i.e., congruence) of the three first- comparisons in the other two dimensions (i.e., zest and mood tone) are appropriate. PMID- 3335757 TI - Poverty and living arrangements among older women: are changes in economic well being underestimated? AB - Poverty rates have fallen more slowly over the last three decades among older women living alone than for other groups of elderly persons. The simultaneous increase in the percentage of elderly women living alone has given rise to speculation that these two phenomena are related. Using 1950 and 1980 Census data this relationship was explored. Over the 30-year period, poverty among elderly women fell by 35.9 percentage points. It would have fallen further if women had not changed the types of households in which they lived, but by only an additional 3 percentage points. The effect of changes in household composition, however, was greatest for the oldest of the elderly individuals. PMID- 3335756 TI - The risk factors of nursing home entry among residents of six continuing care retirement communities. AB - We identified client characteristics related to nursing home entry for 3,316 residents of six continuing care retirement communities with a longitudinal dataset that follows an initially healthy entry cohort for up to 15 years. The Cox Proportional Hazards Model was used for the analysis of survival data that includes censored data. We calculated hazard indices for residents with different characteristics to show the independent effect of these variables on the probability of nursing home entry. Seven variables emerged as statistically significant covariates: sex, marital status, roommate status, entry year into the community, entry age into the community, number of hospitalizations, and community of residence. The community of residence, which in large part reflects system effects on nursing home entry, was found to be the single most important variable explaining variance in the data. Tobit analysis was used to examine the factors associated with multiple nursing home entries and total days per year spent in a nursing home. With a few exceptions, most of the variables listed above were also significant correlates of multiple entries and total days per year spent in a nursing home. PMID- 3335758 TI - Community size differences in service awareness among elderly adults. AB - This article presents findings on community size differences in the awareness of eight services for a sample of 600 elderly persons living in two countries containing a continuum of locales ranging from nonmetropolitan farm areas to the central city of a metropolitan area. The data were collected via indepth personal interviews, and indicate that the total number of services known by elderly persons is related directly to community size. Multiple-regression analysis revealed that community size is the strongest predictor of overall service awareness. However, variation in the awareness of individual services found for elderly residents of different community sizes suggests that the role this variable plays in service awareness is not as straightforward as is often assumed. PMID- 3335759 TI - Predictors of satisfaction with children's help for younger and older elderly parents. AB - In structured interviews, parents aged 60 to 90 described their children's work and family responsibilities, the practical and affective support they exchanged with each of their children, their satisfaction with assistance received from their children, and their values regarding family relationships. Self-reported general health, proximity values, and kin-orientation values predicted satisfaction with children's help for the total sample. For parents aged 74 and younger, proximity values, reciprocity in help exchanges, number of children helping relatives other than the participant, and number of children working outside of the home predicted satisfaction; for parents aged 75 and older, self reported general health and kin-orientation values predicted satisfaction. It is concluded that values regarding families, interdependence, and autonomy provide a critical context for reactions to help by adult children. PMID- 3335760 TI - Humor and health. PMID- 3335761 TI - Confusion: testing versus observation. PMID- 3335762 TI - Behavior problems in an urban nursing home. PMID- 3335763 TI - The need to assess dementia. PMID- 3335765 TI - High risk surgical patients. PMID- 3335764 TI - Analyzing soaps for infection control. PMID- 3335766 TI - Effect of particle size on labeling density for catalase in protein A-gold immunocytochemistry. AB - Effect of particle size on labeling intensity in protein A-gold immunocytochemistry was studied. Catalase labeling of rat liver peroxisomes was used as a labeling model. Ultra-thin sections of Lowicryl K4M-embedded rat liver were stained for catalase with protein A-gold (pAg) probes. Five different sizes of colloidal gold probes, from 5 nm to 38 nm in diameter, were prepared. Labeling intensity decreased as the particle size of the pAg probes increased. The highest labeling was obtained by the 5-nm pAg probe and the lowest by the 38-nm pAg probe. Quantitative analysis also showed that labeling density was inversely proportional to the size of gold particles. The results suggest that the pAg probe with small gold particles has high sensitivity. PMID- 3335767 TI - An investigation of optimal gold particle size for immunohistological immunogold and immunogold-silver staining to be viewed by polarized incident light (EPI polarization) microscopy. AB - We investigated the optimal gold particle size for use with polarized incident light (epi polarization) microscopy with immunogold immunohistological preparation in both immunogold indirect (IGS) and silver-enhanced immunogold silver staining (IGSS) techniques. A range of gold particle sizes from 5 nm-40 nm was used along with tissue of known immunoreactivity with a well-characterized primary monoclonal antibody. Checkerboard titrations were carried out for each technique and for each particle size. The preparations were viewed using a standard polarized incident light microscope and assessed in a semi-quantitative manner. Adequate visualization of gold particles was achieved using the indirect staining method only with a particle size of 40 nm. With silver enhancement (IGSS), particles of all sizes were clearly seen. However, 5-nm particles were considered optimal for this method because of reduced background staining, high titration of antisera possible, and crisp localization of the visual signal. PMID- 3335768 TI - Imaging the distribution of the stable isotopes of nitrogen 14N and 15N in biological samples by "secondary-ion emission microscopy". AB - Thanks to the "secondary-ion emission microscope" (CAMECA IMS 300), we have been able to image the distribution of the stable isotopes of nitrogen 14N and 15N in sections of plant roots (spatial resolution better than 1 micron), as well as to estimate the relative concentrations of these isotopes. The plants used (Lupinus spec.) originated from seeds with natural (i.e., 14N) nitrogen and had been fed for a few days with [15N]-nitrate before sampling. We have found in root sections of 6-day-old plants (prepared at 5 mm from the root tip) a clear-cut regionalization of the distribution of 15N between the vascular cylinder and the cortex. The latter contained approximately 5% 15N (of total nitrogen), whereas the relative concentration of the heavy isotope in the vascular cylinder was significantly lower. The observed concentration difference is probably due to the Casparian strip, which is a barrier for the apoplastic diffusion of solutes from the cortex to the vascular cylinder. PMID- 3335769 TI - Immunohistochemical localization of glutamate dehydrogenase in rat liver: plasticity of distribution during development and with hormone treatment. AB - In adult rat liver, glutamate dehydrogenase is present in high concentrations around the terminal portal (zone 1) and hepatic (zone 3) veins, whereas its concentration is low in the intermediate zone. Although the size and staining intensity of the periportal glutamate dehydrogenase-positive compartment are less than those of the pericentral compartment, it can expand under appropriate endocrine conditions, leading to a homogeneous distribution. At birth, glutamate dehydrogenase is also homogeneously distributed. Glutamate dehydrogenase disappears from the periportal compartment during the first postnatal week and reappears in that compartment after weaning. These observations indicate an independent regulation of glutamate dehydrogenase levels in the periportal and pericentral zone. The size of the periportal glutamate dehydrogenase-containing zone is appreciably smaller than that of carbamoylphosphate synthetase, whereas the pericentral glutamate dehydrogenase-containing zone is appreciably larger than that of glutamine synthetase. The heterogeneous distribution of glutamate dehydrogenase suggests the possibility that, under normal conditions, deamination of glutamate prevails in the periportal compartment and amination of glutamate in the pericentral compartment. PMID- 3335770 TI - Localization of cations by pyroantimonate. II. Electron probe microanalysis of calcium and sodium in skeletal muscle of mouse. AB - A new formulation of the pyroantimonate (PA) method for localization of calcium and sodium is proposed and evaluated in mouse skeletal muscle. This study, performed at the ultrastructural level by means of transmission electron microscopy (TEM) and electron probe microanalysis (EPMA), completes a previous work done at the optical level with analytical ion microscopy (AIM), which enabled us to define the appropriate composition of fixatives. In our present experiments, calcium and sodium were shown localized in various cell structures, e.g., T-tubules, glycogen, granules, nuclei. For AIM, the best fixatives were characterized by PA supersaturation, which resulted in smaller crystals and a high rate of penetration in the presence of paraformaldehyde and either phenol or collidine. Contrary to the findings at the optical level, collidine did not give satisfactory results at the ultrastructural level. The method of floating sections on the microtome trough was an important cause of cation displacement. We found that alkalinization of the floating medium significantly decreased ion loss. The technique also provided an indication of the form of these elements: free or easily liberated cations were precipitated into coarse PA deposits; electron-positive chelates were "stained" by PA; neutral chelates were not stained, but some of them could be detected by EPMA. This PA method should make possible more precise localization of cellular calcium, such as in glycogen metabolism, and perhaps detection of movements of cytoplasmic calcium and sodium. PMID- 3335771 TI - Chromatin structural transitions following histone H1 displacement by phosphatidylserine vesicles and low pH treatment. A multiparametric analysis involving flow cytometry, electron microscopy, and nuclease digestion. AB - We describe several morphological and functional modifications in isolated rat liver nuclei incubated in the presence of phosphatidylserine (PS) multilamellar vesicles (MLV). These effects, which occur through the release of histone H1, induce chromatin decondensation, as shown by electron microscopy and nuclease digestion. Flow cytometry was employed to monitor these changes in chromatin structure in isolated nuclei by means of perpendicular light scatter (PLS) and fluorescence signals. Chromatin decondensation induced by PS or by low pH treatment was accompanied by an increase in perpendicular light scatter and by less efficient binding of ethidium bromide. These flow cytometric findings are peculiar to chromatin decondensation induced by displacement of histone H1. Conversely, chromatin decondensation caused by lowering of the divalent ion concentration, without displacement of histone H1, is characterized only by an increase in perpendicular light scatter. PMID- 3335772 TI - Monoclonal alkaline phosphatase-anti-alkaline phosphatase (APAAP) complex: production of antibody, optimization of activity, and use in immunostaining. AB - A mouse monoclonal antibody, FMC55 (an IgG1), to alkaline phosphatase was prepared and evaluated in immunostaining. Clones producing antibody to alkaline phosphatase were selected using a micro-ELISA which identified antibodies forming active soluble complexes (APAAP) with the enzyme. Conditions that influenced the formation of the complex were investigated by using a quantitative assay in which the complex was captured by a bridging anti-mouse antibody. The ratio of FMC55 to enzyme had a major influence on the activity of the complex. Although all complexes had some activity, those that contained excess antibody had reduced ability to bind to anti-mouse antibody because of competition with excess unlabeled antibody. The optimal complex was formed with 3 micrograms of FMC55 per unit of enzyme. This complex contained neither free enzyme nor free antibody. The molecular weight by gel permeation chromatography was 600,000, giving a composition of two enzyme and two antibody molecules or one enzyme and three antibody molecules. The size of the complex was not altered by adding excess antibody or excess enzyme. Immunoblotting showed that FMC55 bound only to the Mr 140,000 homodimeric form of alkaline phosphatase. The APAAP complex was used in combination with biotin-streptavidin-peroxidase reagent to detect two antigens labeled with two different mouse monoclonal antibodies in the same tissue preparation. PMID- 3335773 TI - Localization of phosphophoryn in rat incisor dentin using immunocytochemical techniques. AB - We studied the distribution of the phosphophoryn present in rat incisors by immunolocalization and histochemical techniques. The polyclonal antibody used reacts with both phosphorylated and de-phosphorylated phosphophoryn. Technical problems encountered in immunostaining and in preparing sections from mineralized dentin were resolved by use of peroxidase-conjugated protein A as the "second antibody" in indirect immunostaining reactions and by surface etching of partially demineralized sections. Staining with anti-rat incisor alpha phosphophoryn antibody showed light staining over the odontoblasts and proximal odontoblastic processes, no stain over the predentin, dense staining over the intertubular dentin, and no stain over the mantle dentin. In the intertubular dentin the stain intensity was directly related to the distribution of mineral. These findings were directly corroborated by staining with Stains All. The mineralization of dentin and the distribution of phosphophoryn within the dentin may be much less uniform than previously supposed. PMID- 3335774 TI - Membrane differentiation markers of airway epithelial secretory cells. AB - We describe here a system for culturing epithelial cells isolated from hamster trachea, which results in a highly enriched population of mucus-secreting cells. The culture system has enabled us to study the process of secretory cell differentiation in vitro. We found that epithelial secretory cells, in vivo and after 5 days in vitro, selectively bind the lectin Helix pomatia agglutinin (HPA) to apical and, to a lesser extent, basolateral surfaces as well as to mucin granules and intracellular secretory organelles. SDS-PAGE gels of detergent extracts of secretory cells cultured for 5 days reveal three HPA-binding glycoproteins with MW of 120 KD, 220 KD, and greater than 400 KD. The high-MW glycoprotein appears identical to mucin, since it is found in secretions from intact trachea and in spent media from 5-day cultures. It does not appear in spent media from 3-day cultures when cells contain few mucous granules and secrete little mucin. The 220 KD HPA-binding glycoprotein is also present in 5 day but not in 3-day cultures. In contrast, the 120 KD glycoprotein is present at both times. HPA-gp120 is a hydrophobic integral membrane protein, whereas HPA gp220 and mucin are hydrophilic and are membrane associated. These studies define three membrane glycoproteins, one of which is specific for the tracheal epithelial secretory cell regardless of its mucous content, whereas the other two glycoproteins correlate with mucin secretion. They also demonstrate that, in the fully differentiated state, mucin is bound in a non-covalent fashion to the apical plasma membrane of the tracheal epithelial secretory cell. PMID- 3335775 TI - Sponge aggregation factor: identification of the specific collagen-binding site by means of a monoclonal antibody. AB - The aggregation factor (AF) from the sponge Geodia cydonium is known to be a complex proteinaceous particle, composed of a series of different (glyco)proteins (Mr lower than 150,000) around a 90S sunburst-like core structure. One of the low Mr proteins is the 47-KD cell binding fragment. We describe a new monoclonal antibody (mAb), III1E6, raised against purified AF particles, which recognizes in tissue slices structures present both on the plasma membrane and in a network like manner in the extracellular space. By applying immunoelectron microscopical, immunoblotting, and immunoaffinity chromatographical techniques, the mAb III1E6 was shown to recognize the core structure of the AF particle. Cell adhesion studies revealed that the mAb does not inhibit AF mediated cell-cell adhesion but abolishes AF-caused attachment of cells to collagen. Electron microscopic data show that III1E6 prevents association of AF particles with collagen fibrils. By applying the techniques of immunoblotting and of protein-protein recognition on the solid phase in vitro, we could formulate the following series of events: the AF particle recognizes, with its 47-KD cell binding fragment, the aggregation receptor protein in the plasma membrane and with its core structure the collagen fibrils. These fibrils interact optionally, either via the same route or via the collagen assembly factor, with an adjacent cell surface. These findings demonstrate that the AF particle is not only the key molecule for cell-cell adhesion but also a component of cell-matrix interactions. PMID- 3335776 TI - Leakage of cathepsin from lysosomes during an early stage of fixation may be related to background adsorption of horseradish peroxidase (HRP) and loss of cell surface HRP-binding sites. PMID- 3335777 TI - Qa-2 antigen encoded by Q7b is biochemically indistinguishable from Qa-2 expressed on the surface of C57BL/10 mouse spleen cells. AB - Qa-2 was immunoprecipitated from the surface of 125I-labeled C57BL/10 (B10) mouse spleen cells and compared with Qa-2 immunoprecipitated from the surface of R1.1 thymoma cells transfected with Q7b. Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that Qa-2 glycoproteins from both of these sources have a relative molecular mass of approximately 37 kDa. After treatment with endoglycosidase F, the Qa-2 polypeptide chains derived from C57BL/10 spleen and Q7b-transfected R1.1 cells displayed identical mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis because of removal of N linked oligosaccharide residues. Furthermore, treatment of Qa-2 proteins from both sources with cyanogen bromide or alpha-chymotrypsin resulted in identical peptide fragmentation patterns. These results therefore provide a biochemical correlation between a cloned Qa-region gene produce expressed on the surface of transfected cells, and the Qa-2 glycoprotein on spleen cells that was described a decade ago by serologic methods. PMID- 3335778 TI - Detection of private and recurrent idiotopes on natural anti-tubulin antibodies by monoclonal anti-idiotopic antibodies. AB - Two monoclonal anti-idiotopic antibodies (anti-Id) were raised in mice against a human monoclonal IgA,K displaying a monospecific anti-tubulin (anti-alpha- and anti-beta-tubulin) activity. One anti-Id (IgG,K) recognized a private idiotope, TID 3.2, present only on the IgA,K immunogen, close to or within the antigen combining site. The other anti-Id (IgM,K) recognized a recurrent idiotope, TID 7.1, outside the paratope and present in normal human and BALB/c mouse serum, on 2 of 11 polyspecific human monoclonal immunoglobulins and on 6 of 11 murine natural monoclonal auto-antibodies exhibiting a widespread anticytoskeletal protein-binding activity. Both the idiotopes were absent on two induced anti tubulin antibodies exhibiting a monospecific anti-alpha- and anti-beta-tubulin specificity. Utilizing competitive and additivity immunoassays, we could show that the polyspecific human and mouse anticytoskeletal antibodies tested, whether bearing the TID 7.1 Id or not, appeared to compete in variable degrees for epitopes on the tubulin molecule recognized by the monoclonal IgA,K but distinct from the epitopes recognized by the induced monospecific anti-tubulin antibodies. The high incidence of the recurrent TID 7.1 idiotope in man and mouse suggests an important physiologic and perhaps regulatory function of this idiotope. Furthermore our data suggest that a restricted family of germ-line genes, highly conserved during phylogeny, may encode for these idiotope-bearing Ig molecules. PMID- 3335779 TI - Characterization of a human basophil-like cell promoting activity. AB - Biologic and biochemical properties of a human basophil-like cell promoting activity (BaPA), which induces growth of metachromatically staining cells from normal bone marrow cells in a liquid culture system have been examined. In order to study this T cell factor, an assay was developed based on the intracellular histamine content of the cultured human bone marrow cells. Many lymphokines, including granulocyte-macrophage colony-stimulating factor, granulocyte colony stimulating factor, interleukin 1 alpha and 1 beta, interleukin 2, and interferon alpha and gamma, did not exhibit any significant activity in the assay. By employing this assay, BaPA was purified approximately 500-fold from lectin stimulated spleen cell-conditioned medium. BaPA has a molecular weight of 23,000 on high performance liquid chromatography gel filtration and displays isoelectric points between 5.8 and 7.3. It is heat stable up to 80 degrees C for 30 min and resistant to 6 M guanidine hydrochloride, whereas it is rather sensitive to sulfhydryl reagents. BaPA has no stimulating activity on mouse bone marrow cells. PMID- 3335781 TI - N-terminal and cDNA characterization of murine lymphocyte antigen Ly-6C.2. AB - The Ly-6C.2 molecule was purified from K36 tumor cells by affinity chromatography and gel filtration. The electrophoretically homogeneous preparation, with m.w. 15,000, was tested with a panel of antibodies that confirmed the presence of the LY-6C.2 epitope. An N-terminal sequence of 39 amino acids was obtained showing 59% homology with the corresponding portion of the Ly-6A.2 polypeptide. Based on the least homologous (29%) 14 amino acid segment, an oligonucleotide probe was constructed, and Ly-6C.2 cDNA was cloned from a BW5147 cDNA library. A 794-base pair cDNA containing the entire coding region had 82% homology with Ly-6A.2 cDNA. The encoded polypeptide sequence of 131 amino acids containing a perfect correlation with the N-terminal sequence data was 63% homologous with that of Ly 6A.2. The greatest homology was in the leader, first 16 N-terminal and last 39 C terminal amino acids. The latter are likely to be important in determining the attachment of glycophosphatidylinositol. Despite results indicating fewer disulfide constraints in the Ly-6C molecule, the predicted sequence contains 10 cysteine residues nearly perfectly matched with those predicted in Ly-6A. PMID- 3335780 TI - Genetics of resistance to the African trypanosomes. VII. Trypanosome virulence is not linked to variable surface glycoprotein expression. AB - The question of linkage of virulence traits to variable surface glycoprotein (VSG) expression in African trypanosomiasis was addressed. Previously we demonstrated that daughter cells arising in mice infected with a genetically homogeneous trypanosome population of Trypanosoma brucei rhodesiense were more virulent than the infecting population (J. A. Inverso and J. M. Mansfield, J. Immunol. 130:412, 1983). These virulent trypanosomes expressed differences in surface phenotype compared with the infecting variant types, and we proposed that virulence may be "linked" to VSG expression. In the present study, however, we have shown that expression of virulence is independent of the VSG phenotype displayed by trypanosome populations. A VSG-identical but highly virulent subpopulation of T. b. rhodesiense LouTat 1 was derived by rapid subpassage and subcloning in immunosuppressed mice. The virulent LouTat 1A subclone derived in this manner killed B10.BR/SgSnJ mice in 3 to 4 days postinfection compared with approximately 60 days for the parent clone, LouTat 1. The virulent subclone LouTat 1A appears to express the same VSG as the less virulent LouTat 1 population, as determined by polyspecific and monoclonal antibody-binding assays, cross-protection tests, and amino acid sequence analyses of the N-terminal portion of the VSG molecules. When LouTat 1 and subclone LouTat 1A were injected into a heterologous host species, multiple variant antigenic types (VATs) arising from each inoculum were isolated and characterized. VATs derived from the virulent subclone were as uniformly virulent for B10.BR mice as LouTat 1A. In summary, these results demonstrate that trypanosome virulence, once expressed, is a stable phenotype that does not seem to be associated with a particular VSG phenotype, nor does virulence change with the expression of different VSG genes. PMID- 3335782 TI - IgA:IgM and IgA:IgA hybrid hybridomas secrete heteropolymeric immunoglobulins that are polyvalent and bispecific. AB - Polyvalent bispecific antibodies were secreted by hybrid hybridoma cells when both parental clones expressed a naturally polymerizing immunoglobulin. Hybrid hybridomas made from IgA lambda 2 anti-trinitrophenyl (TNP) and IgA kappa anti phosphocholine (PC) parental cells secreted polymeric IgA antibodies that bound both TNP and PC. Some of the TNP binding was dissociated from the PC binding under conditions of mild reduction and alkylation suggesting that the bispecific polymeric IgA contained disulfide-linked parental monomers as well as bispecific hybrid monomers. Hybrid hybridomas constructed from IgA lambda 2 anti-TNP and IgM kappa anti-ox erythrocyte parental cells secreted bispecific, polymeric immunoglobulin that contained mu-, alpha-, kappa-, and lambda 2-chains. The mu and kappa-chains dissociated from the alpha- and lambda 2-chains under conditions of mild reduction and alkylation, indicating that both parental monomers had been incorporated into the same polymeric immunoglobulin to form a heteropolymeric antibody molecule. Heterologous pairing of alpha and mu heavy chains in monomers was not detected. Hybrid hybridomas constructed from IgA lambda 2 and IgG3 lambda 2 or IgA lambda 2 and IgG1 kappa parents co-secreted both parental immunoglobulins, but the antibodies secreted by these clones did not form heteropolymers or exhibit heterologous heavy chain pairing. These findings establish that polyvalent, bispecific, polymeric immunoglobulin molecules can be produced by hybrid hybridomas when both parents express a naturally polymerizing class of heavy chain but not when only one parent does. Hybrid hybridomas that produce heteropolymeric immunoglobulins are sources of high avidity bispecific antibodies that may find a number of basic and practical applications. The hybridoma cells that produce these antibodies may provide useful tools for investigating the in situ determinants of immunoglobulin chain association and the regulation of antibody assembly and secretion. PMID- 3335783 TI - Motility of murine lymphocytes during transit through cell cycle. Analysis by a new in vitro assay. AB - The relationship between the basal (spontaneous) motility of murine lymphocytes and their position in the cell cycle was examined in a new collagen gel motility assay system. Concanavalin A-stimulated or control lymphocytes were allowed to locomote into slabs of type I collagen gel. The assay configuration permitted extraction of both total populations and locomotory subpopulations as viable, single-cell suspensions suitable for phenotypic and cell analysis. Concanavalin A stimulation resulted in a significant increase in the mean distance traveled by the leading cell front in 4 hr, from 23 microns (controls) to 67 microns. The estimated percentage of motile cells increased from 0.9 to 2.8%. Similar increases were observed after 18 hr of locomotion. The SIg+, Thy-1+, L3T4+, and Ly-2+ subsets exhibited equivalent increases in motility. Total populations and locomotory subpopulations were allowed to incorporate 5-bromo-2'-deoxyuridine, and their cell cycle profiles were compared by dual parameter anti-5-bromo-2' deoxyuridine, propidium iodide fluorescence analysis. Total population and locomotory subpopulations did not differ significantly with respect to the ratio G0/G1:S, indicating that lymphocytes in these two phases exhibited approximately equal motility. Cells in late S and G2 + M were significantly less motile; locomotory subpopulations contained 60 to 75% fewer G2 + M cells than the total populations from which they were derived. Taken together, the results indicate that the concanavalin A-induced increase in motility commences before S phase and that motility diminishes shortly before or during G2 + M. PMID- 3335784 TI - Lack of cross-reaction in antibody-dependent cellular cytotoxicity between human immunodeficiency virus (HIV) and HIV-related West African strains. AB - Sera from individuals infected with human immunodeficiency virus (HIV) and HIV related West African viruses can mediate high-titered, virus-specific antibody dependent cellular cytotoxicity (ADCC) in all stages of infection. No cross reactive ADCC can be detected between HIV and HIV-related West African strains LAV-2, HTLV-IV, and SBL-6669. Because these two groups of viruses have antigenically distinct envelope glycoproteins, ADCC-mediating antibodies are most likely directed against envelope antigens. For HIV-specific ADCC, this was further confirmed by using sera reacting with HIV envelope but negative for antibodies against viral core antigens. PMID- 3335785 TI - Proportion of antigenic variants induced by in vitro UV irradiation differs in clones derived from a single tumor. AB - The purpose of this study was to examine the capacity of different clones derived from the same tumor to generate highly antigenic cells after in vitro exposure to UV radiation. Cells from the metastatic murine melanoma K1735 and clones of K1735 differing in metastatic potential were exposed to UV radiation in vitro, cloned, and tested for antigenic properties in vivo. Approximately half of the clones isolated after UV irradiation of parental K1735 melanoma cells were highly antigenic (five of nine). Similar treatment of cells of a nonmetastatic clone of K1735 generated clones that were all antigenic (nine of nine). In contrast, only one of nine clones derived from UV-irradiated cells of a highly metastatic clone of K1735 were antigenic. Clones derived from unirradiated cultures were not antigenic variants. The increased antigenicity of cells derived from UV irradiated cultures did not correlate with an increase in expression of cell surface class I major histocompatibility complex antigens. These results demonstrate that the frequency of antigenic variant production after UV irradiation is an intrinsic property of the particular cell line used, and that even cloned cell lines derived from a single tumor differ in their ability to generate antigenic variants after UV irradiation. In addition, they indicate that the increased antigenicity is not necessarily due to a UV-induced increase in expression of cell surface class I histocompatibility antigens. PMID- 3335787 TI - Characterization of superoxide dismutase from mammalian skin epidermis. AB - Superoxide dismutase provides a protective defense mechanism in cellular compartments against the potential cytotoxicity of superoxide anion generated by ultraviolet radiation. Little information is available about the nature of superoxide dismutase in mammalian skin. We report the isolation and characterization of superoxide dismutase from human, guinea pig, and mouse epidermis. Copper-zinc superoxide dismutase was detected in all the mammalian skin specimens examined. Manganese superoxide dismutase was detected in human and guinea pig epidermis but not in the newborn or adult albino CD1 mouse epidermis. Electrophoresis studies of the extracted and partially purified skin superoxide dismutase on polyacrylamide gel slabs in the presence of sodium dodecylsulfate showed the characteristic molecular weights for subunits of 16,500 for copper zinc superoxide dismutase, and 23,500 for mangano superoxide dismutase. Studies under nondenaturing conditions revealed significant differences in the mobility of the enzymes, depending on the sources of superoxide dismutase. The mouse epidermal copper-zinc superoxide dismutase was found similar to the bovine liver copper-zinc superoxide dismutase used as an internal standard. The copper-zinc superoxide dismutase of human skin and guinea pig skin showed activity-stained bands characterized by a higher mobility than the same enzyme from mouse or bovine liver. Quantitative data using the beta-NADH oxidation method indicated a 5-10-fold lower content of superoxide dismutase in mammalian epidermis in comparison with other tissues examined during this study, or compared with reported values in the literature. PMID- 3335786 TI - Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts. AB - H-2-deficient variants, selected from the murine lymphoma RBL-5, were recently shown to be less tumorigenic in syngeneic mice compared with the corresponding H 2-positive wild-type cell line. The present study focused on the detailed cellular interactions leading to the specific rejection of H-2-deficient cells in vivo. In vivo experiments with mixed tumor inocula, measuring either tumor outgrowth or rapid elimination, showed that the presence of H-2-positive lymphoma cells did not suppress the rejection of H-2-deficient cells. Conversely, H-2 deficient cells did not activate a rejection of H-2-positive cells. H-2-deficient cells were selectively eliminated even when they were present in a 10-fold excess compared with the H-2-positive lymphoma cells in the same inoculum. In vitro, H-2 deficient cells were more sensitive to killing by spleen cells from mice treated with interferon or natural killer-inducing agents. The presence of cold H-2 deficient cells did not activate the killing of H-2-positive cells, and H-2 positive cells did not inhibit killing of H-2-deficient cells. Such mixing experiments revealed a more efficient cold target inhibition by the H-2-deficient cells, although no difference was seen between these and the H-2-positive wild type cells in target binding assays. When Thy-1.2+, nylon wool adherent or phagocytic populations were removed from normal spleen effectors, the difference in spontaneous cell-mediated cytotoxicity between the H-2-deficient and the H-2 positive cells persisted. This result was also obtained when spleen cell effectors from nude mice or asialo GM1+ effectors, positively enriched by fluorescence-activated cell sorter, were used. The results show that the selectivity in the rejection of H-2-deficient cells was not determined in the afferent arm alone. The present data fit with a previously proposed model where natural killer cells would bind equally well to both major histocompatibility complex class I negative and class I positive target cells, but only the latter would be able to present a postbinding inhibitory signal allowing them to escape killing which results in outgrowth in vivo and poor cold target competition in vitro. PMID- 3335788 TI - Recruitment of quiescent (G0) cells following epidermal injury is initiated by activation of the phosphoinositol cycle. AB - Under normal circumstances, the rate of production of new cells by the epidermis is rather low, but injury results in a burst of mitotic activity that continues until repair is complete. It is now recognized that most cells of the germinative population are in a resting (G0) state, and "postinjury cell renewal" is the consequence of G0 cells entering the mitotic cycle. The biochemical events triggering this process, however, are unknown. Here we show that phorbol myristate acetate (PMA) is able to induce G0 mobilization in the epidermis of the nude mouse. Further, we demonstrate that amiloride (an inhibitor of the membrane Na+-H+ pump), applied topically to human skin, abolishes almost completely the regenerative response after experimental injury. We suggest that activation of the phosphoinositol cycle may initiate recruitment of G0 cells in the epidermis. PMID- 3335791 TI - Electron microscopic study on cell differentiation in anagen hair follicles in mice. AB - The dorsal and sinus hair follicles from 7-day-old mice of several strains were ultrastructurally examined to study their cell differentiation. The findings were compared with those in human anagen hair follicles. The keratinized cells in the Henle's and Huxley's layers gradually lost their cell volume and finally became thin and lamellar in mice. The outer root sheath (ORS) was composed of two cell layers in the mouse hair bulb. The cells in the outer layer gradually increased in number upwards; the completed outer layer consisted of 2-3, and over 10 cell layers in the mouse dorsal and sinus hair follicles, respectively. These cells produced many membrane-limited, highly electron-dense granules or cementsomes, and finally underwent a keratinization toward the hair canal. The innermost cell (IMC) layer of the ORS formed a unique single-cell layer in mice as well as in humans, although the mouse IMC were much thinner and contained fewer tonofilaments. Accumulation of tonofilaments in the inner side of the cytoplasm and keratohyalin production, but no cementsome production occurred in the mouse IMC. The mouse IMC started to keratinize after the degeneration of the keratinized inner root sheath (IRS) cells. These findings suggest that the lower hair follicle is composed of the IRS layers, the IMC layer, and the outer layer of the ORS in either mice or humans, although there are some morphological differences in cell differentiation in each layer between the two species. PMID- 3335789 TI - Identification of collagen fibrils in scleroderma skin. AB - Skin from early and late stages of scleroderma has been shown to contain large amounts of thin (30-40 nm diameter) collagen fibrils that may be present in bundles or intermingled with large diameter fibrils (90-120 nm). The nature of these fibrils is unknown. Skin biopsies were obtained from involved areas of nine patients with progressive systemic sclerosis (PSS), one case of generalized morphea, one case of morphea, and six normal controls. Intact skin was analyzed by immunoelectron microscopy (IEM), while extracts were subjected to sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE), Western immunoblotting, radioimmunoassay (RIA), and enzyme-linked immunosorbent assay (ELISA). Fine fibrils 20-40 nm in diameter in the mid to lower dermis of scleroderma skin were labeled with antibodies directed against the aminopropeptide (AP) of type III procollagen. Antibodies directed against the AP of type I procollagen labelled fine fibrils in the lower dermis. Larger fibrils (80-120 nm) did not label. pN alpha 1 (III) was found to be present in both normal and scleroderma skin. Extracts of scleroderma skin contained 2.5 times the amount of pN (III) collagen and 3.0 times the amount of fibronectin as did extracts of normal skin. The data indicate that the increase in thin fibrils in scleroderma skin is most likely due to an increase in type III collagen, which retains the AP at its surface. PMID- 3335790 TI - Do oral carotenoids protect human skin against ultraviolet erythema, psoralen phototoxicity, and ultraviolet-induced DNA damage? AB - This study was performed in order to (1) assess the magnitude of a possible protective effect of oral carotenoids on ultraviolet B (UVB)-, ultraviolet A (UVA)-, and psoralen ultraviolet A (PUVA)-induced erythema in human skin and (2) to evaluate whether the postulated prevention of skin cancer by prophylactic administration of carotenoids is based on a decrease in UVB-induced DNA damage. Twenty-three healthy volunteers received oral carotenoids (150 mg/day) for 4 weeks. Serum levels were quantitated, and ranged from 390 to 1710 micrograms/dl. Before and after carotenoid administration, the UVA- and UVB-MEDs and the PUVA MPD were determined by standard phototesting. DNA damage was assessed by autoradiographical measurement of unscheduled DNA synthesis (UDS) following UVB exposure before and after treatment. No statistically significant carotenoid dependent protection was found against UVA, UVB, and PUVA erythema by comparing the pre- and postcarotenoid erythema doses. Also at the DNA level there was no indication of a protective effect that could be detected with the methods employed: the amount of UVB-induced UDS was not decreased after carotenoid treatment. We conclude that (1) carotenoids do not reduce UVB-, UVA-, or PUVA induced erythema in human skin; that (2) reactive oxygen species may not be involved in PUVA-erythema production or, alternatively, carotenoids may not quench these radicals sufficiently in vivo; and that (3) carotenoid protection against UVB-induced carcinogenesis does not operate by reducing the number of mutagenic lesions in DNA. PMID- 3335792 TI - Electron probe analysis of human skin: element concentration profiles. AB - Concentration profiles for the major biological inorganic elements Na, P, S, Cl, and K were measured across human skin using electron probe analysis and analytical electron microscopy. Determinations were made within the cytoplasm of individual cells. Uniform element concentrations were present throughout the viable tissue, whereas element profiles in the stratum corneum were considerably diverse. Phosphorus was practically absent from the stratum corneum. Sulfur (per unit volume) continuously increased from the inner to the outer cell layers of the stratum corneum largely as a result of cytoplasmic water loss as cells migrate to the surface. Potassium was essentially excluded from the inner stratum corneum. Very large gradients for K, Na, and Cl occurred from the middle of the stratum corneum to its outer surface; these gradients are likely the result of the inward diffusion of salts from sweat and could play a variety of physiological roles. The paucity of K and P within the inner stratum corneum suggests these important intracellular solutes (and perhaps others, including water) are recycled within the viable tissue, thus providing a virtual nutrient supply immediately underneath the stratum corneum. Alterations in this recirculation could have a regulatory function in the physiology of this tissue. PMID- 3335793 TI - Human keratinocytes catabolize thymidine. AB - Human neonatal foreskin keratinocytes incorporate exogenous thymidine into DNA and proliferate in vitro even after reaching confluence. Keratinocytes also catabolize thymidine, as reported for the first time below. Stratified cultures of keratinocytes reduced the amount of thymidine in the medium by more than 90% within 2 to 4 h. Consequently, the rate of incorporation of thymidine (0.2 microM, 4 microCi/ml) into DNA was linear for no more than 2 h. Linear incorporation of thymidine into DNA for at least 12 h could be achieved by continual addition of fresh radioactive thymidine to the culture medium. Different tissues have widely differing abilities to catabolize thymidine. Cutaneous catabolism of thymidine shows striking species differences. Soluble extracts from human neonatal foreskin and adult skin, as well as from cultivated human keratinocytes, actively catabolize thymidine. Soluble extracts of skin from mouse, rabbit, or guinea pig do not catabolize thymidine. Extracts from cultivated human fibroblasts and melanocytes have little or no ability to catabolize thymidine. Catabolism of thymidine by keratinocytes has important implications for the use of [3H]thymidine in studies of keratinocyte proliferation and for the use of thymidine analogs in therapy of cutaneous disease. PMID- 3335794 TI - Pathogenesis of brain abscess formation in an infant rat model of Citrobacter diversus bacteremia and meningitis. AB - The pathogenesis of Citrobacter diversus meningitis and brain abscess was studied in infant rats. Two-day-old rats were inoculated intraperitoneally and intranasally with C. diversus. C. diversus strain 4277, lacking the 32,000 molecular-weight outer membrane protein that appears to be a marker for strains causing meningitis in human neonates, was more likely to produce bacteremia, meningitis, and death in rats than was strain 4036, which possesses this outer membrane protein. Strain 4036 was, however, more likely than strain 4277 to produce ventriculitis and brain abscess. In the infant rat, central nervous system involvement by C. diversus begins with bacteremia and leptomeningitis, followed by ventriculitis and direct extension of infection into periventricular brain parenchyma. Large numbers of bacteria persist inside inflammatory cells, an observation suggesting resistance to intraphagocytic killing. Bacterial strain differences, possibly related to the presence of a 32,000-molecular-weight outer membrane protein, may account for histopathologic differences in the brains of infant rats with C. diversus meningitis. PMID- 3335796 TI - Respiratory syncytial virus epidemics: variable dominance of subgroups A and B strains among children, 1981-1986. AB - We examined the distribution of subgroups A and B strains from respiratory syncytial virus during five epidemic years from 1981 to 1986 in Huntington, West Virginia. Of 235 infants and children with respiratory syncytial virus infection, 211 had virus reisolated from frozen throat swab specimens for subgroup characterization by reactivity with a panel of monoclonal antibodies to the G, F, NP, M, and P proteins by using an enzyme immunoassay. We identified 160 (75.8%) strains as subgroup A and 51 (24.2%) as subgroup B. Strains of both subgroups were isolated in all years. Small, but approximately equal, numbers of subgroup B strains were isolated each epidemic year. By contrast, subgroup A strains occurred at least three times as often in all years except 1984-1985. The very low number of subgroup A strains isolated during the 1984-1985 epidemic gave dominance to subgroup B strains. PMID- 3335795 TI - Intraamniotic infection in low-birth-weight infants. AB - Intraamniotic infection (IAI) complicating births of low-birth-weight infants (less than 2500 g) was compared with IAI in births of infants weighing greater than or equal to 2500 g for differences in neonatal and maternal infectious morbidity and mortality, as well as differences in microbiological isolates in amniotic fluid. Four hundred four cases of clinically diagnosed IAI were prospectively evaluated. Thirty-seven patients (9.2%) delivered neonates less than 2500 g, and 367 patients (90.8%) delivered neonates greater than or equal to 2500 g. The low-birth-weight group had a significant increase in the incidence of sepsis (16.2% vs. 4.1%, P = .005) and death from sepsis (10.8% vs. 0%, P less than .001). Additional intrapartum conditions that might further predispose the low-birth-weight group to an increased risk of sepsis were not evident. Evaluation of the amniotic fluid did not demonstrate any increase in prevalence of group B streptococci, Escherichia coli, or enterococci in the low-birth-weight group. The presence of gram-negative anaerobes was significantly increased, however, in low-birth-weight pregnancies with IAI (59.5% vs. 31.6%, P = .001). PMID- 3335797 TI - Chronic group A coxsackievirus infection in agammaglobulinemia: demonstration of genomic variation of serotypically identical isolates persistently excreted by the same patient. PMID- 3335798 TI - Demonstration of hepatitis D virus RNA in patients with chronic hepatitis. PMID- 3335800 TI - Human immunodeficiency virus in glial cells? PMID- 3335799 TI - Bacteriuria in women with long-term catheters: paired comparison of indwelling and replacement catheters. PMID- 3335801 TI - Use of the chitin-synthesis inhibitor nikkomycin to treat disseminated candidiasis in mice. PMID- 3335802 TI - Recurrent broviac catheter infections. PMID- 3335803 TI - Staphylococcus saprophyticus bacteremia. PMID- 3335804 TI - Infection with vancomycin-resistant "streptococci" due to Leuconostoc species. PMID- 3335805 TI - Use of an enzyme-linked immunosorbent assay and of inhibition studies to distinguish between antibodies to cardiolipin from patients with syphilis or autoimmune disorders. AB - We report a VDRL-enzyme-linked immunosorbent assay (ELISA) that enabled us to distinguish between the antibodies to cardiolipin from patients with autoimmune disorders and those from patients with syphilis. Additional studies using inhibition experiments with phospholipid liposomes, as well as ELISAs with a variety of phospholipid antigens, showed that antibodies to phospholipids from patients with syphilis bind cardiolipin (best when presented as the VDRL antigen) but exhibited little cross-reactivity with negatively charged phospholipids. On the other hand, antibodies to phospholipids from patients with autoimmune disorders exhibited little or no binding to the VDRL antigen but cross-reacted with both cardiolipin and negatively charged phospholipids. These findings may explain why antibodies to phospholipids only from patients with autoimmune disorders may have lupus anticoagulant activity and why they are associated with thrombosis, fetal loss, and thrombocytopenia. PMID- 3335806 TI - Localization of urinary tract infection in elderly, institutionalized women with asymptomatic bacteriuria. AB - We determined the site of urinary tract infection in 51 elderly, institutionalized women (mean age, 80.5 years) with asymptomatic bacteriuria by using the Fairley bladder washout technique. Thirty-four (67%) infections were localized in the kidney and 17 (33%) in the bladder. Women with renal infection were older than those with bladder infection (81.9 vs. 77.6 years of age; P = .04). The antibody-coated bacteria test had a sensitivity of 58%, specificity of 71%, positive predictive value of 82%, and negative predictive value of 43% for upper-urinary-tract infection. A quantitative urinary leukocyte count of greater than or equal to 20 leukocytes/mm3 had a positive predictive value of 80% and a negative predictive value of 88% for upper-urinary-tract infection. This study suggests that the majority of elderly, institutionalized women with asymptomatic bacteriuria have upper-urinary-tract infection. Both the antibody-coated bacteria test and the quantitative urinary leukocyte count may be useful as noninvasive tests for localization of urinary tract infection in this population. PMID- 3335807 TI - Characteristics of adherence to plastic tissue culture plates of coagulase negative staphylococci exposed to subinhibitory concentrations of antimicrobial agents. AB - Adherence and hydrophobic properties characteristic of 6-h cultures of coagulase negative staphylococci on plastic tissue culture plates were determined after the organisms had been treated for up to an additional 6 h with subinhibitory concentrations of antimicrobial agents. Clindamycin, erythromycin, norfloxacin, tunicamycin, and vancomycin had no effect. Cephalothin, chloramphenicol, gentamicin, imipenem, methicillin, novobiocin, polymyxin B, rifampin, and tobramycin had varied effects. Most changes induced by these agents resulted in differing degrees of inhibition of adherence. However, an increase in adherence of 65% was observed for one strain, RP14 (ATCC 35981), with rifampin treatment. Hydrophobicity of coagulase-negative staphylococci treated with antimicrobial agents measured by using a biphasic system with hexadecane showed excellent correlation with adherence (r = .958, P less than .0005), a result suggesting that adherence of these bacteria in this system depends heavily on hydrophobic surface moieties. Transmission electron microscopy of drug-treated coagulase negative staphylococci revealed only an increase in cell-wall thickness, regardless of whether adherence was increased or decreased. PMID- 3335808 TI - Epidemics of pneumonia caused by TWAR, a new Chlamydia organism, in military trainees in Finland. AB - Four epidemics of pneumonia in military trainees in Finland have been shown, by microimmunofluorescence serology, to have been caused by TWAR, a recently described, unique Chlamydia organism. The epidemics occurred in four different garrisons from 1957 to 1985. Each lasted approximately six months, and epidemics occurred during all seasons of the year. The attack rate varied from 60 to 80 per 1000 men. Routine laboratory tests for respiratory agents suggested that these epidemics represented the only clusters of patients since 1970 who were positive for antibody to Chlamydia by complement fixation. From these epidemics, 62 of 70 paired sera that were positive for Chlamydia had antibody diagnostic of recent TWAR infection. Although the conscripts with pneumonia were hospitalized, the illnesses were relatively mild, and none were life threatening. Three conscripts had two episodes of TWAR pneumonia separated by three weeks to three months. Prompt treatment with tetracycline depressed the antibody response. PMID- 3335809 TI - The contribution of pneumococcal cell wall to the pathogenesis of experimental otitis media. AB - We studied the contribution of pneumococcal cell wall to the pathogenesis of otitis media in chinchillas after middle ear inoculation of killed, encapsulated type 7F Streptococcus pneumoniae; killed, unencapsulated R6 S. pneumoniae; and isolated R6 pneumococcal cell wall. Ears inoculated with encapsulated and unencapsulated pneumococci had significantly higher concentrations of polymorphonuclear and mononuclear leukocytes and lysozyme in middle ear fluid and developed more epithelial metaplasia and granulation tissue than did saline inoculated ears. The mean concentration of lysozyme in middle ear fluid was higher in ears inoculated with killed, unencapsulated than encapsulated pneumococci. The middle ear mucoperiosteum of ears inoculated with pneumococcal cell wall showed significantly more polymorphonuclear leukocytes, epithelial metaplasia, subepithelial congestion, and granulation tissue than did control ears. Because nonviable, unencapsulated pneumococci and pneumococcal cell wall caused middle ear inflammation in the chinchilla model of otitis media, it is possible that cell envelope and cell wall components released during bacterial lysis may contribute to chronic otitis media with effusion in humans. PMID- 3335810 TI - Herpes zoster in African patients: a clinical predictor of human immunodeficiency virus infection. AB - A recent episode or a history of herpes zoster was found in 30 (11%) of 284 patients hospitalized with human immunodeficiency virus (HIV) infection at Mama Yemo Hospital, Kinshasa, Zaire. Of 146 African patients with a history of herpes zoster who were referred to us by physicians at the Mama Yemo Hospital, 133 (91%) were HIV seropositive. The clinical characteristics of the herpes zoster episodes did not differ between HIV-seropositive and -seronegative individuals, except that 23% of the HIV-seropositive patients experienced recurrences compared with none of the HIV-seronegative patients (P = .05). No patient developed a generalized herpes zoster eruption, and only patients with ophthalmic zoster developed related complications. Patients who experienced severe pain during their herpes zoster attack lost more weight than did those who had only minor pain (P = .0003). PMID- 3335811 TI - Characterization of the regulation of complement-derived chemotactic factors in blunt trauma. PMID- 3335812 TI - Salmonellosis in nurses: lack of transmission to patients. PMID- 3335814 TI - Microbiology of non-puerperal breast abscesses. PMID- 3335813 TI - Five-year immunologic memory in Swedish volunteers after oral cholera vaccination. PMID- 3335815 TI - Excessive serum concentrations of acyclovir and neurotoxicity. PMID- 3335816 TI - Parenteral therapy for antibiotic-associated pseudomembranous colitis. PMID- 3335817 TI - Rhodotorula rubra peritonitis in a child undergoing intermittent cycling peritoneal dialysis. PMID- 3335818 TI - Changes in the hair of black patients with AIDS. PMID- 3335819 TI - Clinical response and peak concentrations of aminoglycosides. PMID- 3335820 TI - Effect of spleen cell conditioned medium on megakaryocytopoiesis in a short-term bone marrow culture system. AB - The effect of pokeweed mitogen-stimulated spleen cell conditioned medium (PWCM) on the proliferation of megakaryocytes and megakaryocyte progenitor cells (CFU-M) was studied with a short-term liquid culture (STLC) system. Adherent and nonadherent cells were sampled daily for acetylcholinesterase-positive cells and CFU-M. The proliferative capacity of CFU-M was determined by culturing cells from STLC in secondary methylcellulose cultures and counting the number of megakaryocytes per colony. Positive dose-related effects were observed between the number of megakaryocytes and CFU-M in liquid culture and the concentration of PWCM in the culture. In contrast, the proliferative capacity of CFU-M was lower in cultures containing high concentrations of PWCM compared with cultures containing low concentrations of PWCM. Furthermore, mean megakaryocyte diameter was significantly smaller in cultures containing high levels of PWCM compared with cultures with low concentrations. These data suggest that at low levels of conditioned medium, megakaryocytopoiesis is characterized by production of fewer CFU-M with a higher proliferative capacity and fewer large megakaryocytes. In turn, high concentrations of PWCM promote the production of a greater number of CFU-M with reduced proliferative capacity and an increased number of small megakaryocytes. PMID- 3335821 TI - Preservation of in vitro function of platelets stored in the presence of inhibitors of platelet activation and a specific inhibitor of thrombin. AB - We prepared platelet concentrates (PCs) in an experimental anticoagulant consisting of citrate-phosphate-dextrose-adenine formula 1 (CPDA-1) containing inhibitors of platelet activation (prostaglandin E1 and theophylline) and a specific thrombin inhibitor (hirudin or D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone-2HCl). Over a 15-day storage period, these PCs showed by in vitro markers (pH, lactic dehydrogenase, PO2, PCO2, glucose consumption, morphology, and hypotonic shock recovery) greatly improved function and integrity relative to PCs in CPDA-1 only. At day 10 of storage, the experimental PCs had higher pH (P = 0.02), better morphology scores (P less than 0.001), more rapid recovery from hypotonic shock (P = 0.03), and higher PCO2 levels (P less than 0.001) than controls in CPDA-1 only. Additional storage time increased these differences to a significance level of p less than 0.01 in all tests. The experimental anticoagulant was less effective when hirudin was absent. Plasma pH was well maintained, and less glucose was consumed in the experimental anticoagulant without the aid of an increase of buffering capacity or gas transport. These findings indicate that thrombin and platelet activation play a major role in the development of the platelet storage lesion. PMID- 3335822 TI - Autoantibodies and cell-to-cell detachment in pemphigus. PMID- 3335823 TI - Complement fixation by pemphigus antibody. IV. Enhanced epidermal cell detachment in the absence of human plasminogen. AB - It has been reportedly previously that complement enhances pemphigus vulgaris antibody-induced epidermal cell detachment. The present studies were designed to eliminate the possibility of the human plasminogen-plasmin system contributing to the cell detachment observed in previous complement-mediated studies. To assay for the presence of protease contamination in the reagents, a simple, sensitive, caseinolytic-fluorometric assay was used. Confluent murine or human epidermal cell cultures were incubated with pemphigus IgG with and without complement and plasminogen. Detached epidermal cells, as determined by light microscopy and cell counter analysis, were enumerated at 48 hours. Incubating pemphigus IgG with complement resulted in marked cell detachment, compared with minimal cell detachment when pemphigus IgG was incubated with plasminogen. Culture media were collected after 48 hours and assayed for activation of plasminogen. It was determined that the added plasminogen had not been activated, particularly in experiments where significant detachment was observed. The plasminogen could still be activated by streptokinase and urokinase. These studies suggest that epidermal cell detachment in pemphigus appears to be mediated at least in part by complement activation. PMID- 3335824 TI - Malaria in beta-thalassemic mice and the effects of the transgenic human beta globin gene and splenectomy. AB - To investigate the protective effects of beta-thalassemia against malaria, rodent malaria parasites were studied in C57BL/6J mice with beta-thalassemia, in mice in which the thalassemia had been transgenically corrected with the human beta A globin gene, and in hematologically normal mice. In thalassemic mice, Plasmodium chabaudi adami infection was inhibited and peak parasitemia was variably delayed. In transgenically corrected mice, infection proceeded as in normal mice. Plasmodium berghei infection proceeded more rapidly in thalassemic mice, but survival was not different. Splenectomized normal mice displayed high-level parasitemia that peaked twice and persisted as a low-level parasitemia for more than 20 days after normal intact mice were free of all parasites. Splenectomized thalassemic mice showed a delay of 5 days in attaining peak parasitemia, but the parasitemia persisted as in normal splenectomized mice. Thus, for P. chabaudi, which displayed no preference for immature erythrocytes, beta-thalassemia offers enhanced resistance for the host. However, for P. berghei, which preferentially invades reticulocytes, thalassemia is not protective. The protective effects of the normal mouse spleen were observed, but the paradoxical facilitation of parasite growth by the thalassemic spleen is a new finding that will require further experimentation to explain. This new in vivo laboratory documentation of thalassemic protection against some rodent malaria parasites may serve as a useful model in further efforts to control this major infectious disease. PMID- 3335826 TI - Neurologic abnormalities in cobalamin deficiency are associated with higher cobalamin "analogue" values than are hematologic abnormalities. AB - Serum cobalamin "analogue" levels were estimated by the discrepancy in cobalamin results with radioassays done with pure intrinsic factor and R binder in 364 patients with low cobalamin levels. No differences were found among the various causes of low cobalamin levels, except for the lower "analogue" levels among pregnant women. However, 76 patients with low cobalamin levels and primarily neurologic (spinal cord, neuropathic, cerebral, or a combination of these) symptoms had significantly higher "analogue" levels than 19 patients with primarily hematologic abnormalities. Moreover, the "analogue" levels correlated with hemoglobin values and were significantly higher in patients without megaloblastic changes in their bone marrow than in patients with megaloblastosis. An analysis limited to 47 patients with pernicious anemia yielded similar findings. The seven patients with only neurologic abnormalities had higher "analogue" levels than did the nine patients with only hematologic abnormalities. Because of the higher "analogue" levels, the assay done with R binder failed to register low cobalamin levels in 33 of 76 patients with low cobalamin levels and primarily neurologic abnormality (compared with only two of 19 with hematologic abnormality) and in 10 of 20 patients with pernicious anemia who had neurologic abnormalities (compared with only two of 12 without such abnormalities). These differences between patients with hematologic disturbances and patients with neurologic disturbances, and the inverse relationship of "analogue" level with severity of anemia, suggest that the disproportionate accumulation of analogues may explain why some patients with cobalamin deficiency display neurologic abnormalities while others do not. PMID- 3335825 TI - Dose-dependent effects of postmenopausal estrogen and progestin on antithrombin III and factor XII. AB - The frequent use of estrogen and progestin replacement for treatment in postmenopausal women makes assessment of its effect on the coagulation system of interest. Although the amount of estrogen used to achieve the desired therapeutic effect is lower than the lowest doses in oral contraception, the age and medical condition of this population may amplify any hormone-induced risk. The common impression is that postmenopausal replacement therapy does not increase risk for thromboembolic disease, but no large epidemiologic studies of estrogen replacement have addressed that question. In this randomized prospective study, we examined the effects of varying low doses of an estrogen-progestin preparation on the titers of clotting factors in postmenopausal women. The coagulation factors selected for investigation were among those that have been reported to be significantly altered in the plasma samples of high-dose estrogen users. There were no changes in prothrombin time, factor X, fibrinogen, factor VII, or fibrinopeptide A in any of the hormone-treated groups. Mild but significant shortening of the partial thromboplastin time and elevation of factor XII titer were noted in all treatment groups. The titer of antithrombin III was reduced in the group given 20 micrograms ethinyl estradiol, but not in the groups given 5 or 10 micrograms. The clinical significance of these changes is difficult to determine in postmenopausal women receiving sex hormone replacement. However, we have not noted any thromboembolic episodes in our volunteers after a 1-year follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335827 TI - Use of arabinogalactan to obtain washed murine platelets free of contaminating plasma proteins and appropriate for studies of function, morphology, and thrombopoiesis. AB - A simplified procedure for preparing washed murine platelets, free of contaminating plasma proteins, has been developed. Platelet-rich plasma (PRP) was prepared from diluted whole blood from C57BL/6N mice by two centrifugations at 100 x g for 12 minutes. Platelets were concentrated and then washed by centrifugation through isosmolar 10% arabinogalactan (Stractan). Platelet recovery was 85% +/- 6% (1 SD) (n = 10) from whole blood to PRP and 86% +/- 4% (1 SD) (n = 6) from PRP to Stractan-washed platelets. Overall recovery of platelets with this technique was 73% +/- 10% (1 SD). Contamination of platelets with plasma proteins could not be detected with use of unlabeled platelets that had been incubated with radiolabeled plasma proteins followed by washing with Stractan. The Stractan-washed platelets were assessed for function by using aggregometry. The response of Stractan-washed platelets to collagen and thrombin was identical to that of unwashed platelets. Stractan-washed platelets did not respond to 20 mumol/L adenosine diphosphate unless supplemented with 12% platelet free plasma. The morphology of the Stractan-washed platelets indicated that degranulation had not occurred. With use of antibodies directed against the alpha granule membrane protein GMP-140 or fibrinogen, no evidence of secretion or plasma protein contamination was observed. The use of this method resulted in an improved assay for the rate of thrombopoiesis, based on detection of radioactive proteins in newly synthesized platelets, by eliminating contamination by radioactive plasma proteins. Our results indicate that this procedure is a convenient method for the separation of platelets from platelet-rich plasma, free of plasma proteins, which are suitable for bioassays, functional studies, and morphologic investigations. PMID- 3335828 TI - Antigenic variation of a cysteine-rich protein in Giardia lamblia. AB - The WB isolate of Giardia lamblia expresses a cysteine-rich 170-kD surface antigen (CRP170) that undergoes antigenic variation. An (6E7), cytotoxic for isolates expressing CRP170, was used in another study to select antigenic variants from clones of the WB isolate of Giardia. CRP170 was replaced by surface labeled bands ranging in size from approximately 50 to 170 kD. In this study, mAb 6E7 was used to isolate a 1-kb portion of the CRP170 gene (M2-1) from a lambda gt 11 expression library. The M2-1 clone hybridized to a 5.4-kb transcript from isolates expressing CRP170 but did not hybridize to RNA from antigenic variants. Evidence was found for frequent rearrangements at the CRP170 gene locus. DNA sequencing of the M2-1 clone revealed the presence of long tandem repeats. The putative amino acid sequence of M2-1 reveals a 12% cysteine content, and CRP170 is readily labeled in vivo with cysteine. PMID- 3335829 TI - Aging and arteriosclerosis. The increased proliferation of arterial smooth muscle cells isolated from old rats is associated with increased platelet-derived growth factor-like activity. AB - In vivo studies have suggested that the aorta from an old animal responds to injury with an exaggerated proliferation of smooth muscle cells (SMCs) compared with the response of this aorta from a young animal. In this study we compared proliferation of SMCs derived from uninjured old (less than 19 mo) and young (3-4 mo) rat aortas. Old SMCs grew more rapidly than young SMCs in the presence of medium containing competence factors (10% FCS or platelet-derived growth factor [PDGF]) as well as in their absence (2% PDS or serum-free media) as determined both by a short-term thymidine incorporation assay and by cell counts. Lysates prepared from old SMCs that had been grown in the absence of serum or PDGF stimulated proliferation of target cells more than lysates prepared from young SMCs; the effect was inversely related to cell density of the SMCs. This stimulatory effect of lysates was completely blocked by antibody to PDGF. After the growth-promoting activity of lysates was eliminated by anti-PDGF, growth inhibiting activity was revealed. Lysates prepared from old SMCs had significantly less capacity to inhibit target cell growth. In the presence of exogenous heparin both the serum- or PDGF-stimulated proliferation and serum-free proliferation of old SMCs were decreased to the level of proliferation of young SMCs. These results suggest that the balance between growth-promoting and growth inhibiting factors is altered in SMCs from old rats. This may contribute to the increased proliferative capacity of these cells in culture and may facilitate the development of atherosclerosis with age. PMID- 3335830 TI - Sequence analysis of cDNA coding for a major house dust mite allergen, Der p 1. Homology with cysteine proteases. AB - A cDNA clone coding for Der p 1, a major allergen from the house dust mite Dermatophagoides pteronyssinus, has been sequenced. It codes for a 222 residue mature protein with a derived molecular weight of 25,371 and contains 1 potential N-glycosylation site. In addition, the cDNA appears to code for a 13 residue proregion, and an incomplete signal peptide. The deduced sequence shows a high degree of homology with animal and plant cysteine proteases, particularly in the region of the contact residues making up the active site. Southern analysis of genomic DNA indicates that the allergen is coded by a noncontiguous gene. These data will now facilitate epitope mapping studies. PMID- 3335832 TI - Nucleotide sequence of the capsid protein gene and 3' non-coding region of papaya mosaic virus RNA. AB - The nucleotide sequences of cDNA clones corresponding to the 3' OH end of papaya mosaic virus RNA have been determined. The 3'-terminal sequence obtained was 900 nucleotides in length, excluding the poly(A) tail, and contained an open reading frame capable of giving rise to a protein of 214 amino acid residues with an Mr of 22930. This protein was identified as the viral capsid protein. The 3' non coding region of PMV genome RNA was about 121 nucleotides long [excluding the poly(A) tail] and homologous to the complementary sequence of the non-coding region at the 5' end of PMV RNA. A long open reading frame was also found in the predicted 5' end region of the negative strand. PMID- 3335833 TI - Nucleotide sequence of segment S10 of the rice dwarf virus genome. AB - DNA complementary to the tenth largest (S10) of the 12 genome segments of rice dwarf virus (RDV) was cloned and its sequence was determined. This genome segment is 1319 nucleotides in length and has a single long open reading frame extending for 1059 nucleotides from the first AUG triplet (residues 27 to 29). The predicted translation product comprises 352 amino acids and has a mol. wt. of 39094. RDV transcripts synthesized in vitro have the same polarity as the plus strand of the genome. Terminal sequences were (+) 5' GGUA---UGAU 3' and (-) 3' CCAU---ACUA 5' which are similar to those of wound tumour virus RNA. PMID- 3335831 TI - Biology of Giardia lamblia. Detection of N-acetyl-D-glucosamine as the only surface saccharide moiety and identification of two distinct subsets of trophozoites by lectin binding. AB - Lectins and glycosidases of known sugar specificity were used as probes to analyze the surface carbohydrate moieties of G. lamblia trophozoites and in particular to determine whether chitin or oligomeric D-GlcNAc is present in the trophozoite form of the parasite as well as on the cyst. Of 13 lectins with varying sugar specificity, only D-GlcNAc-specific lectins bound specifically to the trophozoite surface as determined by light microscopy and EM. A striking finding was the identification of two distinct subsets of trophozoites, distinguished by reactivity with WGA and detected by light microscopy and EM as well as by flow cytometry. Unlike the cyst wall, the trophozoite D-GlcNAc residues were resistant to chitinase treatment. In contrast N-acetyl-beta-D glucosaminidase abolished WGA binding suggesting that the lectin binds to terminal beta-linked D-GlcNAc residues. These residues were identified as being present on surface glycoproteins by Western blotting of parasite membrane proteins using WGA as a probe. This study identifies D-GlcNAc as the only saccharide moiety detectable by lectin binding on the surface of G. lamblia trophozoites and demonstrates that in contrast to the cyst, chitin is not present in the trophozoite. In addition two distinct subsets of trophozoites were identified based on reactivity with WGA and may represent varying stages of differentiation from trophozoite to cyst. PMID- 3335834 TI - The phenomenology of posttraumatic stress disorders following a natural disaster. AB - This study examined the utility of the DSM-III diagnostic criteria for posttraumatic stress disorder (PTSD) in a high-risk group of 50 firefighters who had had an intense exposure to a natural disaster 8 months before being interviewed. Follow-up over the next 3 years allowed examination of the ability of these diagnostic criteria to predict a pattern of chronic posttraumatic morbidity. They predicted a pattern of chronic disorder, demonstrated by the finding that eight of the 15 subjects who had definite or borderline PTSD at 8 months remained symptomatic 3 years later. A disturbance of attention and concentration appeared to be the best predictor of chronic PTSD. The longitudinal course of posttraumatic morbidity in these 50 firefighters was compared with a matched group of 96 uninterviewed subjects 11 and 29 months after the disaster. Although the interview provoked an emotional catharsis in a number of firefighters, the long-term morbidity in the two groups was comparable. Fourteen subjects who did not have PTSD continued to experience intense imagery 8 months after the disaster. This observation raises questions about whether such thoughts and feelings have adequate specificity as diagnostic criteria for PTSD in a group that has recently been exposed to a traumatic event. PMID- 3335835 TI - The longitudinal course of posttraumatic morbidity. The range of outcomes and their predictors. AB - This study examined the longitudinal course, over a 25-month period, of posttraumatic morbidity in a group of 469 firefighters exposed to a bushfire disaster. The patterns of posttraumatic morbidity were defined by the General Health Questionnaire. Contrary to expectation, an acute pattern of morbidity was less common than the delayed-onset or chronic forms. Predisaster variables were found to be as important in the onset and course of the disorder as were the firefighters' losses or extent of exposure to the disaster. These data suggest that exposure to an extreme trauma is necessary but not sufficient to explain the onset and pattern of posttraumatic morbidity. PMID- 3335836 TI - DSM-III personality disorders and family history of mental illness. AB - This report investigates the way in which the presence of a personality disorder (PD) in probands affects the frequency of psychiatric disorders in relatives. Four proband groups--panic, panic plus a PD, major depression, and depression plus a PD--were given the Family History-Research Diagnostic Criteria and the Family History for DSM-III Anxiety and Personality Disorders. Information was gathered on 730 first-degree relatives. Panic patients with a PD had higher incidences of panic and panic plus a PD in relatives. There was increased depression in relatives of probands with either depression or a PD. Alcoholism appeared highest in relatives of probands who had combined depression and a PD. PMID- 3335837 TI - GABAergic inhibition on dopamine cells of the fish retina: a [3H]dopamine release study with isolated fractions. AB - Inner retinal cells including dopamine (DA) cells were isolated and fractionated from the carp (Cyprinus carpio) retina by an enzyme cell dissociation and metrizamide gradient centrifugation method. When gamma-aminobutyric acid (GABA) antagonists (bicuculline and picrotoxin) were added into the perfusate over such a cell fraction, they stimulated the release of [3H]DA which had been preloaded in the cell fraction. The action of GABA antagonists was dose and Ca2+ dependent. Their minimal effective concentration was very low (0.5 microM). A similar action was elicited by high K+. In the presence of excess GABA, this stimulatory action of GABA antagonists and high K+ on [3H]DA release was completely abolished. To interpret the action of GABA antagonists on DA cells, isolated cell fractions were preincubated with GABAse. After such a treatment, the stimulatory effects of GABA antagonists and high K+ on [3H]DA release were differentiated from each other; the former disappeared whereas the latter remained unchanged. The data strongly suggest that GABA inhibits the DA release from retinal DA cells and thus the GABA antagonists affect [3H]DA release from cell fractions not by a direct membrane action but by a disinhibition mechanism via GABA receptors on the DA cell bodies. PMID- 3335839 TI - Antioxidant action and photosensitizing effects of three different chlorpromazines. AB - Chlorpromazine inhibits by about 60% the lipid peroxidation stimulated by Fe2+/ascorbate in liposomes and the lipid peroxidation stimulated by cumene hydroperoxide in microsomes. Under the same conditions, two new synthetic derivatives of chlorpromazine, i.e., a N-benzoyloxymethylchlorpromazine and a N pivaloyloxymethylchlorpromazine, induce no more than a 20% inhibition. On the other hand, when the different chlorpromazines are entrapped in liposomes and subsequently irradiated with near-UV light, they act as photosensitizing agents giving rise to lipid peroxidation. The latter is quite extensive in the presence of chlorpromazine or N-pivaloyloxymethylchlorpromazine, whereas it is drastically lower in the presence of N-benzoyloxymethylchlopromazine. The N benzoyloxymethylchlorpromazine molecule, despite its low photodynamic effect, retains its neuroleptic properties. The possible mechanisms of the antioxidant and prooxidant actions of these compounds are discussed. PMID- 3335838 TI - Acetylcholine mobilization in a sympathetic ganglion in the presence and absence of 2-(4-phenylpiperidino)cyclohexanol (AH5183). AB - The present experiments measured the release of acetylcholine (ACh) by the cat superior cervical ganglia in the presence of, and after exposure to, 2-(4 phenylpiperidino)cyclohexanol (AH5183), a compound known to block the uptake of ACh by cholinergic synaptic vesicles. We confirmed that AH5183 blocks evoked ACh release during preganglionic nerve stimulation when approximately 13-14% of the initial ganglial ACh stores had been released; periods of rest in the presence of the drug did not promote recovery from the block, but ACh release recovered following the washout of AH5183. ACh was synthesized in AH5183-treated ganglia, as determined by the synthesis of [3H]ACh from [3H]choline, and this [3H]ACh could be released by stimulation following drug washout. The specific activity of the released ACh matched that of the tissue's ACh, and thus we conclude that ACh synthesized in the presence of AH5183 is a releasable as pre-existing ACh stores once the drug is removed. We tested the relative releasability of ACh synthesized during AH5183 exposure (perfusion with [3H]choline) and that synthesized during recovery from the drug's effects (perfusion with [14C]choline: the ratio of [3H]ACh to [14C]ACh released by stimulation was similar to the ratio in the tissue. These results suggest that the mobilization of ACh for release by ganglia during recovery from an AH5183-induced block is independent of the conditions under which the ACh was synthesized. Unlike nerve impulses, black widow spider venom (BWSV) induced the release of ACh from AH5183-blocked ganglia, even in the drug's continued presence. Venom-induced release of ACh from AH5183-treated ganglia was not less than the venom-induced release from tissues not exposed to AH5183. This effect of BWSV was attributed to the action of the protein, alpha latrotoxin, because an anti-alpha-latrotoxin antiserum blocked the venom's action. ACh synthesized during AH5183 exposure was labelled from [3H]choline, and subsequent treatment with BWSV released [3H]ACh with the same temporal pattern as the release of total ACh. To exclude a nonexocytotic origin for the [3H]ACh released by BWSV, ganglia were preloaded with [3H]diethylhomocholine to form [3H]acetyldiethylhomocholine, an ACh analogue excluded from vesicles; the venom did not increase the rate of [3H]acetyldiethylhomocholine efflux. It is concluded that a vesicular ACh pool insensitive to the inhibitory action of AH5183 might exist and that this vesicular pool is not mobilized by electrical stimulation to exocytose in the presence of AH5183, but it is by BWSV. PMID- 3335840 TI - Possible involvement of glutathione S-transferases in the cell growth of C6 astroglioma cells. AB - The changes of glutathione S-transferase activity were investigated using rat brain astroglioma C6 cells that were synchronized at different phases of the cell cycle. The enzyme showed two significant activity peaks at G2 and G1 phases. Furthermore, when C6 glioma cells were exposed to a culture medium supplemented with specific glutathione S-transferase inhibitors, ethacrynic acid and caffeic acid, cell growth was remarkably suppressed. These results suggest that glutathione S-transferases may be closely related to the mechanism of cell proliferation. PMID- 3335841 TI - Effect of crush lesion on radiolabelling of ganglioside in rat peripheral nerve. AB - Left sciatic nerves of adult male Sprague-Dawley rats were crushed and allowed to recover for 0, 1, 2, 4, 7, or 14 days. At each of these times both L-5 dorsal root ganglia were injected with 100 microCi of [3H]glucosamine. Two days later, dorsal root ganglia, lumbosacral trunks, and sciatic nerves were removed bilaterally. The amounts of radiolabelled ganglioside in crushed lumbosacral trunks were consistently higher than in the controls, with the largest difference occurring within 2 days from simultaneous crush and injection to killing (specimens labelled day 0). The largest difference in the amount of radiolabelled ganglioside between crushed and control sciatic nerve (4-9 days from crush to killing) occurred later than that of lumbosacral trunk, but no significant difference occurred within the first 3 days following crush. There was only a slightly higher radioactivity in gangliosides totalled from all three anatomical specimens of crushed than in control nerves. The neutral nonganglioside lipid and acid-precipitable fraction followed patterns of synthesis and accumulation similar to those of the gangliosides. These findings indicate that after nerve crush gangliosides, glucosamine-labelled neutral nonganglioside lipids, and glycoproteins accumulate close to the proximal end of the regenerating axon. This accumulation could serve as a reservoir to increase the ganglioside concentration in the growth cone membrane. PMID- 3335842 TI - 4-(O-benzylphenoxy)-N-methylbutylamine (bifemelane) and other 4-(O-benzylphenoxy) N-methylalkylamines as new inhibitors of type A and B monoamine oxidase. AB - 4-(O-Benzylphenoxy)-N-methylbutylamine (Bifemelane, BP-N-methylbutylamine), a new psychotropic drug, was found to inhibit monoamine oxidase (MAO) in human brain synaptosomes. It inhibited type A MAO (MAO-A) competitively and type B (MAO-B) noncompetitively. BP-N-methylbutylamine had a much higher affinity to MAO-A than an amine substrate, kynuramine, and it was a more potent inhibitor of MAO-A than of MAO-B. The Ki values of MAO-A and -B were determined to be 4.20 and 46.0 microM, respectively, while the Km values of MAO-A and -B with kynuramine were 44.1 and 90.0 microM, respectively. The inhibition of MAO-A and -B by BP-N methylbutylamine was found to be reversible by dialysis of the incubation mixture. MAO-A in human placental and liver mitochondria and in a rat clonal pheochromocytoma cell line, PC12h, was inhibited competitively by BP-N methylbutylamine, while MAO-B in human liver mitochondria was inhibited noncompetitively, as in human brain synaptosomes. BP-N-methylbutylamine was not oxidized by MAO-A and -B. The effects of other BP-N-methylalkylamines, such as BP N-methylethylamine, -propylamine, and -pentanylamine, on MAO activity were examined. BP-N-methylbutylamine was the most potent inhibitor of MAO-A, and BP-N methylethylamine and -propylamine inhibited MAO-B competitively, whereas BP-N methylbutylamine and -pentanylamine inhibited it noncompetitively. Inhibition of these BP-N-methylalkylamines on MAO-A and -B is discussed in relation to their chemical structure. PMID- 3335843 TI - DARPP-32 and phosphatase inhibitor-1, two structurally related inhibitors of protein phosphatase-1, are both present in striatonigral neurons. AB - DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein of Mr = 32,000) and phosphatase inhibitor-1, two previously characterized inhibitors of protein phosphatase-1, were identified in both the neostriatum and the substantia nigra. Phosphatase inhibitor-1 was partially purified from bovine caudate nucleus and found to be distinct from DARPP-32 in some of its biochemical properties. The neuronal localization of DARPP-32 and phosphatase inhibitor-1 within the rat neostriatum and substantia nigra was investigated by studying the effects of kainic acid. Injection into the neostriatum of kainic acid, which destroys striatonigral neurons and striatonigral fibers, decreased the amounts of DARPP-32 and phosphatase inhibitor-1 to the same extent, both in the lesioned neostriatum and in the ipsilateral substantia nigra. The specific activity of protein phosphatase-1 in the neostriatum was unaffected by kainic acid. The results indicate that, in rat brain, DARPP-32 and phosphatase inhibitor-1 are both present in striatal neurons and in striatonigral fibers, and that they probably coexist in at least a subpopulation of striatonigral neurons. In contrast, protein phosphatase-1 does not appear to be enriched in any specific neuronal subpopulation in the neostriatum. PMID- 3335844 TI - Regulation of norepinephrine uptake by adenine nucleotides and divalent cations: role for extracellular protein phosphorylation. AB - This study examined the hypothesis that ATP, released together with norepinephrine (NE) from brain noradrenergic nerve terminals, may serve as a cosubstrate for an extracellular protein phosphorylation system that regulates the reuptake of the transmitter, NE. The possible regulation of high-affinity uptake (uptake 1) of [3H]NE by divalent cations and ATP, both of which are involved in protein phosphorylation, was examined in rat cerebral cortical synaptosomes. A marked inhibition of uptake 1 by 5'-adenylylimidodiphosphate [App(NH)p], a nonhydrolyzable, competitive antagonist of ATP, was observed. A similar inhibition of uptake was observed when Ca2+ and Mg2+ were both omitted from the incubation medium. App(NH)p distinguished the actions of Ca2+ from those of Mg2+: Ca2+-stimulated uptake 1 was blocked by App(NH)p; Mg2+-stimulated uptake was not. In parallel experiments, the patterns of protein phosphorylation in crude and purified preparations of synaptosomes were examined under conditions similar to those used in uptake assays. A striking correlation was found between the inhibition of uptake 1, by either App(NH)p or Ca-omission, and inhibition of the phosphorylation of one specific, 39,000-dalton, Ca2+-dependent, protein component in synaptosomes. This 39K protein was distinct from the alpha subunit of pyruvate dehydrogenase, a mitochondrial protein of similar electrophoretic mobility. These findings are consistent with the possibility that an ectokinase on synaptosomes utilizes extracellular ATP and Ca2+ in phosphorylating a protein(s) associated with the regulation of NE uptake. PMID- 3335845 TI - A similar calmodulin-binding protein expressed in chromaffin, synaptic, and neurohypophyseal secretory vesicles. AB - The presence of calmodulin-binding proteins in three neurosecretory vesicles (bovine adrenal chromaffin granules, bovine posterior pituitary secretory granules, and rat brain synaptic vesicles) was investigated. When detergent solubilized membrane proteins from each type of secretory organelle were applied to calmodulin-affinity columns in the presence of calcium, several calmodulin binding proteins were retained and these were eluted by EGTA from the columns. In all three membranes, a 65-kilodalton (63 kilodaltons in rat brain synaptic vesicles) and a 53-kilodalton protein were found consistently in the EGTA eluate. 125I-Calmodulin overlay tests on nitrocellulose sheets containing transferred chromaffin and posterior pituitary secretory granule membrane proteins showed a similarity in the protein bands labeled with radioactive calmodulin. In the presence of 10(-4) M calcium, eight major protein bands (240, 180, 145, 125, 65, 60, 53, and 49 kilodaltons) were labeled with 125I-calmodulin. The presence of 10 microM trifluoperazine (a calmodulin antagonist) significantly reduced this labeling, while no labeling was seen in the presence of 1 mM EGTA. Two monoclonal antibodies (mAb 30, mAb 48), previously shown to react with a cholinergic synaptic vesicle membrane protein of approximate molecular mass of 65 kilodaltons, were tested on total membrane proteins from the three different secretory vesicles and on calmodulin-binding proteins isolated from these membranes using calmodulin-affinity chromatography. Both monoclonal antibodies reacted with a 65-kilodalton protein present in membranes from chromaffin and posterior pituitary secretory granules and with a 63-kilodalton protein present in rat brain synaptic vesicle membranes. When the immunoblotting was repeated on secretory vesicle membrane calmodulin-binding proteins isolated by calmodulin affinity chromatography, an identical staining pattern was obtained. These results clearly indicate that an immunologically identical calmodulin-binding protein is expressed in at least three different neurosecretory vesicle types, thus suggesting a common role for this protein in secretory vesicle function. PMID- 3335846 TI - Effects of amphetamine on protein synthesis and energy metabolism in mouse brain: role of drug-induced hyperthermia. AB - Changes in brain protein synthesis activity, and in brain levels of glucose, glycogen, and several high-energy phosphate metabolites, were evaluated under conditions of amphetamine-induced hyperthermia in mice. Protein synthesis showed a striking dependence on rectal temperature (TR), falling abruptly at TR above 40 degrees C. A similar result was obtained following direct heating of the animals. Protein synthesis activity in liver showed the same temperature dependence observed for brain. Increased synthesis of a protein with characteristics of the major mammalian stress protein, hsp 70, was demonstrated in both brain and liver following amphetamine administration. Brain protein synthesis showed significant recovery within 2 h after amphetamine administration whereas that of liver remained below 30% of control activity, suggesting significant temporal and quantitative differences in the response of individual tissues to elevated temperatures. Brain glycogen levels after amphetamine administration were significantly lower under conditions of ambient temperature which resulted in more severe drug-induced hyperthermia but did not correlate as strikingly as protein synthesis with the temperatures of individual animals. Brain glycogen also fell in animals whose temperatures were increased by brief exposure at high ambient temperature. Brain glucose levels did not consistently change with hyperthermia. Slight decreases in high-energy phosphates with increasing TR were likely the result of fixation artifact. These results demonstrate the fundamental role of hyperthermia in the reduction of protein synthesis in brain and other tissues by amphetamine, and suggest that temperature also constitutes a significant source of variability in the effects of this drug on brain energy metabolism, in particular glycogenolysis. PMID- 3335847 TI - Benzodiazepine enhancement of gamma-aminobutyric acid-mediated chloride ion flux in rat brain synaptoneurosomes. AB - Benzodiazepine agonists such as Ro 11-6896 [B10(+)], diazepam, clonazepam, and flurazepam were found to enhance muscimol-stimulated 36Cl- uptake into rat cerebral cortical synaptoneurosomes. The rank order of potentiation was B10(+) greater than diazepam greater than clonazepam greater than flurazepam. These benzodiazepines had no effect on 36Cl-uptake in the absence of muscimol. Further, the inactive enantiomer, Ro 11-6893 [B10(-)], and the peripheral benzodiazepine receptor ligand Ro 5-4864 did not potentiate muscimol-stimulated 36Cl- uptake at concentrations up to 10 microM. In contrast, the benzodiazepine receptor inverse agonists ethyl-beta-carboline-3-carboxylate and 6,7-dimethoxy-4-ethyl-beta- carboline-3-carboxylic acid methyl ester inhibited muscimol stimulated 36Cl- uptake. Benzodiazepines and beta-carbolines altered the apparent K0.5 of muscimol stimulated 36Cl- uptake, without affecting the Vmax. The effects of both benzodiazepine receptor agonists and inverse agonists were reversed by the benzodiazepine antagonists Ro 15-1788 and CGS-8216. These data further confirm that central benzodiazepine receptors modulate the capacity of gamma-aminobutyric acid receptor agonists to enhance chloride transport and provide a biochemical technique for studying benzodiazepine receptor function in vitro. PMID- 3335848 TI - About the coupling of acetylcholine hydrolysis and choline uptake at cholinergic nerve terminals. PMID- 3335849 TI - Synaptosome preparations. PMID- 3335850 TI - Characterization of a dipeptidyl aminopeptidase from bovine adrenal medulla. AB - A dipeptidyl aminopeptidase was partially purified from a supernatant fraction of bovine adrenal medulla by gel filtration and anion-exchange chromatography. From gel filtration, the apparent molecular weight of the enzyme was 68,100 and its pH optimum was 9.5. Its Km for hydrolysis of the synthetic substrate arginylarginine beta-naphthylamide was 5.5 X 10(-6) M. The enzyme was inhibited by metal ion chelating agents and thiol blocking agents, suggesting the requirement for both a metal ion and an active cysteine residue for its activity. Several peptides were cleaved by the dipeptidyl aminopeptidase involving the sequential removal of dipeptides from the N-terminus. Biologically active peptides, such as leucine enkephalin, methionine-enkephalin, and angiotensin II, were hydrolyzed by the dipeptidyl aminopeptidase although opioid peptides with a length greater than five amino acid residues were not susceptible to hydrolysis. Other peptides with a blocked N-terminus (neurotensin, bombesin) or a proline residue adjacent to a potential cleavage site (substance P) were not hydrolyzed. The ability of this dipeptidyl aminopeptidase to degrade certain neuropeptides suggests that it could be involved in neuropeptide degradation. PMID- 3335851 TI - Incorporation of glycerol and ethanolamine into glycerophospholipid in rat brain areas during bicuculline-induced convulsive seizures. AB - The effect of bicuculline-induced convulsive seizures on lipid metabolism has been studied in four brain areas (cerebellum, cerebral cortex, hippocampus, and brainstem) using [2-3H]glycerol and [1,2-14C]ethanolamine as radioactive lipid precursors administered simultaneously with bicuculline. Twelve minutes after the administration, the uptake of radioactivity depended both on brain area and treatment, being generally higher in convulsing rats. The uptake of glycerol was influenced to a larger extent than that of ethanolamine and increased during convulsions, but its incorporation into lipids did not. In contrast, the amount of ethanolamine incorporated into lipids increased during bicuculline-induced seizures. The difference in behavior of glycerol and of ethanolamine is also indicated by the decrease of the 3H/14C ratio of phosphatidyl-ethanolamine in various brain areas during convulsions. It is, therefore, evident that the metabolism of the two precursors is affected differently by seizures. PMID- 3335852 TI - Purification of choline acetyltransferase from the locust Schistocerca gregaria and production of serum antibodies to this enzyme. AB - Choline acetyltransferase (ChAT; EC 2.3.1.6) was purified from the heads of Schistocerca gregaria to a final specific activity of 1.61 mumol acetylcholine (ACh) formed min-1 mg-1 protein. The molecular mass of the enzyme as determined by gel filtration is 66,800 daltons. The final enzyme preparation showed one major band at 65,000 daltons on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, which corresponds with the native molecular mass of the enzyme, a band at 56,000 daltons, and two bands at 40,500 and 38,000 daltons. Antibodies raised against ChAT in rabbit react only with the active band on native gel after Western blotting. They strongly react with the 65,000-dalton polypeptide band on Western blots of SDS gel separation of pure preparation of enzyme and with both the 65,000- and 56,000-dalton bands after SDS gel separation of crude extract. PMID- 3335853 TI - Blood-brain transport of thiamine monophosphate in the rat: a kinetic study in vivo. AB - To calculate the kinetic parameters of thiamine monophosphate transport across the rat blood-brain barrier in vivo, different doses of a [35S]thiamine monophosphate preparation with a specific activity of 14.8 mCi.mmol-1 were injected in the femoral vein and the radioactivity was measured in arterial femoral blood and in the cerebellum, cerebral cortex, pons, and medulla 20 s after the injection. This short experimental time was used to prevent thiamine monophosphate hydrolysis. Thiamine monophosphate was transported into the nervous tissue by a saturable mechanism. The maximal transport rate (Jmax) and the half saturation concentration (Km) equaled 27-39 pmol.g-1.min-1 and 2.6-4.8 microM, respectively. When compared with that of thiamine, thiamine monophosphate transport seemed to be characterized by a lower affinity and a lower maximal influx rate. At physiological plasma concentrations, thiamine monophosphate transport rate ranged from 2.06 to 4.90 pmol.g-1.min-1, thus representing a significant component of thiamine supply to nervous tissue. PMID- 3335854 TI - Characterization of a cytosolic protein (P36) isolated from pig brain by benzodiazepine-affinity chromatography. AB - Benzodiazepine-affinity chromatography, on a column of 1012S-Sepharose, resulted in the detection and purification of a binding protein (P36) from the cytosolic fraction of pig cerebral cortex. Purified P36 was enriched over 3,500-fold in a single step and was recovered with an efficiency of 50-60%. Analysis of the purified preparation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis demonstrated a single polypeptide of Mr 36,000. The Stokes radius (3.44 nm) and sedimentation coefficient (4.43S) indicated that purified P36 is a dimeric protein. Analysis of the amino acid composition of P36 revealed a relatively high content of the hydrophobic amino acids, valine and leucine. Immunoblotting of several pig tissue preparations with an antiserum raised against purified P36 demonstrated approximately equal enrichment of P36 in cerebral cortex, cerebellum, and adrenal glands. Lesser enrichment was observed in kidney and liver, whereas a number of other tissues displayed no immunoreactivity. The gamma-aminobutyrate/benzodiazepine receptor complex and P36 showed no immunological cross-reactivity. High-affinity binding activity for [3H]Ro 15-4513, [3H]flunitrazepam, or [3H]PK11195 was not detected in preparations of purified P36. However, the ability of the gamma aminobutyrate/benzodiazepine receptor inverse agonists, methyl- and ethyl-beta carboline-3-carboxylate, to inhibit the binding of P36 to 1012S-Sepharose at relatively low concentrations indicates that P36 exhibits a degree of binding specificity. PMID- 3335855 TI - Induction of N-glycosylation activity in cultured embryonic rat brain cells. AB - Developmental changes in protein N-glycosylation activity have been studied using cultures of dissociated fetal rat brain cells as an in vitro model system. These cultures undergo an initial phase of neurite outgrowth and cell proliferation (4 6 days in culture), followed by a period of cellular differentiation. N Glycosylation activity has been measured by assaying the incorporation of [2 3H]mannose into dolichol-linked oligosaccharides and glycoprotein over a period of 1-25 days in culture. This study revealed a marked induction of N glycosylation activity beginning at approximately 1 week of culture. [2 3H]Mannose incorporation into the oligosaccharide-lipid intermediate fraction and glycoprotein reached maximal values between 12 and 16 days of culture and declined thereafter. The major dolichol-linked oligosaccharide labeled by the brain cell cultures was shown to be Glc3Man9GlcNAc2 by HPLC analysis. Parallel incorporation studies with [3H]leucine showed that the increase in protein N glycosylation was relatively higher than a concurrent increase in cellular protein synthesis observed during the induction period. Maximal labeling of glycoprotein corresponded to the period of glial differentiation, as indicated by a sharp rise in the marker enzymes, 2',3'-cyclic nucleotide 3'-phosphohydrolase (an oligodendroglial marker) and glutamine synthetase (an astroglial marker). The results describe a developmental activation of the N-glycosylation pathway and suggest a possible relationship between N-linked glycoprotein assembly and the growth and differentiation of glial cells. PMID- 3335856 TI - Choline acetyltransferase activity in the rat brain cortex homogenate, synaptosomes, and capillaries after lesioning the nucleus basalis magnocellularis. AB - Stereotaxic lesions of the nucleus basalis magnocellularis were made unilaterally in male Wistar rats with either kainic or ibotenic acid, using the contralateral side as control. Differences in behavior, body weight, and survival were observed between the kainic and ibotenic acid-treated rats. One week after surgery, the rats were sacrificed and the effect of the lesions on choline acetyltransferase activity was measured in brain cortex homogenate, synaptosomes, and capillaries. In kainic acid-lesioned rats, choline acetyltransferase activity decreased in homogenate and synaptosomes of the ipsilateral side with respect to that of the contralateral side; but the ibotenic acid lesion, which also reduced the ipsilateral choline acetyltransferase activity in homogenate, showed a rather different effect on the enzymatic activity of the synaptosomes. There were also differences between the effect of kainic and ibotenic acid lesions on choline acetyltransferase activity in the capillaries of the ipsilateral side with respect to that of the contralateral one. However, capillary choline acetyltransferase activity of the treated rats was in both sides three times higher than that of unoperated rats. PMID- 3335857 TI - Differential release of enkephalin and enkephalin-containing peptides from perfused cat adrenal glands. AB - We have compared the enkephalin-like material derived from proenkephalin released from perfused cat adrenal glands stimulated with pilocarpine (5 X 10(-4)M) and nicotine (5 X 10(-6) M). In addition, two doses of acetylcholine (10(-5) and 10( 4) M) and 50 mM K+ were tested. Free Met-enkephalin immunoreactivity and total Met-enkephalin immunoreactivity, as determined by enzymatic digestion of large enkephalin-containing fragments, were coreleased with catecholamines. Free Met enkephalin immunoreactivity represented 13% of total immunoreactivity for nicotinic stimulation, 46% for pilocarpine, 33% for 10(-5) M acetylcholine, 22% for 10(-4) M acetylcholine, and 16% for 50 mM K+. Analysis of the perfusate by gel filtration showed that 80% of the total Met-enkephalin immunoreactivity whose release was induced by pilocarpine was eluted in fractions corresponding to fragments of low molecular weight, whereas these fractions accounted only for 10% of the total Met-enkephalin immunoreactivity whose release was induced by nicotine. HPLC analysis of low-molecular-weight peptide fractions revealed that Met-enkephalin, Met-enkephalin-Arg-Gly-Leu, and Met-enkephalin-Arg-Phe represented 69% of total Met-enkephalin immunoreactivity whose release was induced by pilocarpine. These results indicate that selective activation of muscarinic receptors is followed by release of low-molecular-weight material, whereas nicotine application also yielded high-molecular-weight peptides. Furthermore, increasing the acetylcholine concentration from 10(-5) to 10(-4) M and using 50 mM K+ increased proportionally the high-molecular-weight peptide secretion. Results are discussed in relation to the existence of a heterogeneous population of granules either in the same cell or in different cells, containing proenkephalin-derived peptides. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335858 TI - Assay of 2-hydroxyputrescine in various regions of rat brain by gas chromatography-mass spectrometry. AB - 2-Hydroxyputrescine in seven regions of single rat brains was measured with a sensitive, specific assay by gas chromatography-mass spectrometry. The regions were the cerebral cortex, cerebellum, medulla oblongata, hypothalamus, striatum, hippocampus, and midbrain. The level of 2-hydroxyputrescine was very high in the cerebral cortex and cerebellum, high in the medulla oblongata, hypothalamus, and hippocampus, and low in the striatum and midbrain. The level of 2 hydroxyputrescine in the cerebellum was significantly higher than in the striatum and midbrain. PMID- 3335859 TI - Adenosine inhibition of histamine-stimulated inositol phospholipid hydrolysis in mouse cerebral cortex. AB - The effects of adenosine on inositol phospholipid hydrolysis in mouse cerebrocortical slices were examined. Despite having no effect alone, adenosine and some structural analogues inhibited histamine-stimulated accumulation of inositol phosphates in a concentration-dependent manner. The responses to carbachol, noradrenaline, 5-hydroxytryptamine, and elevated KCl levels were unaffected. The effect of adenosine was on the maximal response to histamine rather than on its EC50. Several adenosine antagonists competitively blocked the inhibition due to adenosine. The results are discussed in relation to the previously reported enhancement of histamine-stimulated hydrolysis of inositol phospholipids in guinea pig brain. PMID- 3335860 TI - Inability of [125I]Sar1, Ile8-angiotensin II to move between the blood and cerebrospinal fluid compartments. AB - The angiotensin II competitive antagonist [125I]-Sar1, Ile8-angiotensin II was not transported from the vascular space to the cerebroventricular space in either intact or nephrectomized rats. In addition [125I]Sar1, Ile8-angiotensin II lacked the capacity to move in the opposite direction over a 20-min collection period following cerebroventricular infusion. These data suggest that angiotensins lack the capacity to move freely between the blood and cerebrospinal fluid compartments and are consistent with the notion that blood-borne and cerebroventricular angiotensins access different receptor populations. PMID- 3335861 TI - K+-dependent stimulation of dopamine synthesis in striatal synaptosomes is mediated by protein kinase C. AB - Dopamine synthesis rate was measured in striatal synaptosomes. Removal of Na+ increased synthesis rate; this was blocked in Ca2+-free medium and by addition of the Ca2+/calmodulin inhibitor N-6-aminohexyl-5-chloro-1-naphthalenesulfonamide (W7). The increase in dopamine synthesis rate caused by the addition of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was blocked by the protein kinase C inhibitor polymyxin B. K+-stimulated synthesis was unchanged in Ca2+-free medium or by addition of W7; it was blocked by polymyxin B. The effect of 50 mM K+ was additive with that of 8-Br cyclic AMP and of Na+ removal; the combined effect of 50 mM K+ and TPA was no greater than that of either alone. These results suggest that stimulation of dopamine synthesis in striatal synaptosomes by 50 mM K+ is mediated by protein kinase C. PMID- 3335862 TI - Biosynthesis of neutral glucocerebroside homologues in the absence of myelin assembly after nerve transection. AB - The biosynthesis of myelin-associated glycolipids during various stages of myelination was studied by in vitro incorporation of [3H]Gal, [3H]Glc, or [35S]sulfate into the endoneurium of rat sciatic nerve. In the normal adult nerve, where the level of myelin assembly is substantially reduced and Schwann cells are principally involved in maintaining the existing myelin membrane, [3H]Gal was primarily incorporated into monogalactosyl diacylglycerol (MGDG) and the galactocerebrosides (GalCe) with lower levels of incorporation into the sulfatides. Such incorporation was enhanced 35 days after crush injury of the adult rat sciatic nerve, which is characterized by active myelin assembly. In contrast, at 35 days after permanent nerve transection where there is no axonal regeneration or myelin assembly, the incorporation of [3H]Gal or [3H]Glc into GalCe was nearly undetected whereas the incorporation of [3H]Gal into MGDG was completely inhibited. Instead, the 3H-labeled glycolipids in transected nerve were identified as the glucocerebrosides (GlcCe) and oligohexosylceramide derivatives with tetrahexosylceramide being a major product. In contrast, [35S]sulfate was incorporated into endoneurial sulfatides in the transected nerve, which suggests that endogenous GalCe rather than newly synthesized GalCe served as the substrate for the sulfotransferase reaction. The GlcCe homologues are not considered as constituents of the myelin membrane but are likely plasma membrane components synthesized in the absence of myelin assembly. It is likely that the cells responsible for GlcCe biosynthesis are Schwann cells, since they comprise 90% of the total endoneurial cell area in the distal nerve segment at 35 days after transection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335863 TI - Fatty acid transport through the blood-brain barrier. AB - Across the cerebral capillaries, the anatomical locus of the blood-brain barrier, the unidirectional influxes of the saturated fatty acids, octanoic and myristic acids, and the unsaturated essential fatty acid, linoleic acid, were measured. Employing an in situ rat brain perfusion technique that allows control of perfusate composition and accurate measurement of perfusate-to-brain fatty acid transport, we found that both [14C]octanoic and [14C]myristic acids were transported through the blood-brain barrier in vivo, in large part, by a specific, probenecid-sensitive transport system. However, the transport of [14C]linoleic acid was not probenecid sensitive. With 0.5 microM fatty acid but no plasma proteins in the perfusate, the permeability-surface area constant was higher for myristic acid (4.8 X 10(-2) X s-1) than for octanoic and linoleic acids (1.5 and 1.2 X 10(-2) X s-1, respectively). Approximately 70, 30, and 25% of the [14C]myristic, [14C]octanoic, or [14C]linoleic acids, respectively, were extracted from the perfusate. PMID- 3335864 TI - Requirement of ATP for exocytotic release of catecholamines from digitonin permeabilized adrenal chromaffin cells. AB - Cultured chromaffin cells were preincubated with digitonin to deplete endogenous ATP from the cell cytoplasm. Catecholamine release from these digitonin pretreated cells was then studied in the presence and absence of exogenous ATP to elucidate a possible involvement of the cytoplasmic ATP in the exocytotic process. The preincubation of the cells with digitonin in the ATP-free permeabilizing medium resulted in a marked decline of the releasing response to a calcium challenge. Furthermore, the declined activity of catecholamine release caused by digitonin pretreatment was restored by the presence of ATP, but not by other adenine nucleotides, and this recovery was observed in a manner dependent on the concentration of ATP. These findings, therefore, seem to indicate that a decrease in the releasing activity of the digitonin-pretreated cells may be due to the removal of endogenous ATP from the cytoplasmic space of the cells, thus suggesting that the cytoplasmic ATP may be involved in the exocytotic mechanism of catecholamine secretion. PMID- 3335865 TI - Biochemical defect of the hph-1 mouse mutant is a deficiency in GTP cyclohydrolase activity. AB - A hyperphenylalaninemic mouse mutant, hph-1, has been identified in the progeny of mice treated with the mutagen ethylnitrosourea. Phenylalanine hydroxylase activity levels in mutant liver lysates are reduced relative to normal, but correction for the amount of enzyme protein present demonstrates that the specific activity of this enzyme is normal in mutant mice. Quinonoid dihydropteridine reductase activity is also normal. GTP-cyclohydrolase activity levels are essentially absent early in life and greatly diminished later in life. This finding has significant implications for the study of catecholamine neurotransmitter synthesis because GTP-cyclohydrolase catalyzes an important step in the de novo synthesis of tetrahydrobiopterin, an enzyme cofactor required for the synthesis of 3,4-dihydroxyphenylalanine (DOPA) and serotonin. PMID- 3335866 TI - Glutamate dehydrogenase activity is markedly higher in a "Golgi-Bergmann"-like glial clone than in other astroglial cell lines. AB - Glutamate appears to be the neurotransmitter of granule cells, the major neuronal population of the cerebellar cortex. To determine the role of astroglial cells in the synthesis of glutamate, we have measured the specific activity of glutamate dehydrogenase (GDH) in clonal cell lines that might be the in vitro equivalents of the different cerebellum astroglial cell types. In conditions where GDH operates in the direction of glutamate synthesis, the specific activity of GDH measured in the "Golgi-Bergmann"-like clone was 4-6 times higher than in the "velate protoplasmic"- or "fibrous-like" astrocytic clones. These data correlate well with the intense immunoreactivity to GDH in Golgi-Bergmann astrocytes in vivo that has been recently reported. PMID- 3335867 TI - Case-control studies of screening. PMID- 3335869 TI - The effectiveness of cervical screening: a population-based case-control study. AB - The cervical smear histories of 36 women with invasive cervical cancer were compared to those of 120 age-matched controls, drawn from local registrar's offices. Of the cases 47% were screened at least once, while for the controls this figure was 68%. The relative risk of getting invasive cervical cancer for women screened at least once compared to women who were never screened was 0.32. The most important confounding factor was age at first intercourse. Contrary to other studies however, it was found that women who were younger when having first intercourse were screened more often. After correcting the relative risk of screened vs unscreened for age at first intercourse, the relative risk became 0.22. When the length of the interval since the last smear was considered, the relative risk was 0.18 when the smear was made between 2 and 5 years earlier and 0.30 when this smear was made more than 5 years earlier. These results support the assumption that screening is effective in the prevention of invasive cancer of the uterine cervix. Even a screening interval of more than 5 years provides considerable protection. PMID- 3335868 TI - Residential mobility during pregnancy: implications for environmental teratogenesis. AB - Although most teratogens are suspected to act early in the first trimester of pregnancy, birth defects monitoring programs and etiologic studies usually use residence at birth as a proxy measure for residence in the first trimester in searching for environmental teratogens. Because of the high mobility of the U.S. population, residence misclassification can potentially alter inferences concerning environmental teratogens. To evaluate this potential bias, data from the population-based Maryland Birth Defects Reporting and Information System were analyzed. In 1984, the system ascertained 295 infants with one or more of 12 sentinel defects. Of these cases, 59 (20%) mothers reported they have changed address between the time of conception and the time of birth, and 22 have moved to a different county. The residential mobility rate varied by demographic variables and was highest among white women, in the age group 20-24 years. If residence at birth is used as a screening test for residence at conception, it can be shown that in the presence of an environmental teratogenic exposure, misclassification of exposure increases with increasing mobility rate, and population exposure frequency. Such misclassification tends to weaken associations between residence and birth defects and may lead to missing environmental teratogens. This analysis emphasizes the need to use residence information early in pregnancy rather than exclusively at birth. PMID- 3335870 TI - Odds ratio estimation in a steady-state population. AB - A three-state Markov process is used to model a steady-state population. The classical P = ID equation is derived, as well as a number of identities originally reported by Miettinen (Am J Epidemiol 1976; 103: 226-235) and Freeman and Hutchison (Am J Epidemiol 1980; 112: 707-723. Ibid. 1986; 124: 134-149). Using theoretical and empirical methods it is demonstrated that the odds ratio derived from a prevalence-prevalence case-control study conducted in a steady state population will generally be a biased estimate of the incidence density ratio. However the bias will not likely be of practical importance unless the incidence density ratio is at least 10 or more. PMID- 3335871 TI - Haematologic parameters as risk factors for cardiac infarction, in an occupational health care setting. AB - It is still controversial, whether moderately high haematocrit (Ht) and haemoglobin (Hb) values are risk factors for coronary heart disease. Using the computerized data-system of the Periodical Medical Examination (PME) of Phillips' International Electrical Company, a case-control study was carried out. Cases were male workers (n = 104, from 50 to 60 years of age) who had suffered a first, non-fatal myocardial infarction, and who had had a PME prior (on the average 16 months) to the occurrence of infarction. For each case two age-matched healthy controls were selected from the PME-attendancy list (= 208). For each subject information was abstracted from the PME-records about haematologic parameters and covariates (smoking, cholesterol, blood pressure, pulse-rate, weight, height, FEV5, consumption of antihypertensive agents). After dichotomizing the haematocrit and haemoglobin values at their whole sample means (0.46 l/l and 9.7 mmol/l respectively) in "low" (lower than or equal to the mean) and "high" (greater than the mean), crude odds-ratio's of 2.7 (95% CI: 1.6-4.6) and 2.1 (95% CI: 1.2-3.6) were found for Ht and Hb respectively, when comparing "high" with "low" levels. The associations between Ht and Hb, and the occurrence of myocardial infarction were still present after controlling for covariates using multiple logistic regression models, entering the continuous variables with their exact values. After adjustment, mean corpuscular volume (MCV) also appeared to be correlated with infarction. Our results confirm the hypothesis that moderately high haematocrit and--to a lesser extent--haemoglobin and MCV-values are risk factors for the occurrence of myocardial infarction. PMID- 3335872 TI - The effect of psychosocial factors on lung cancer mortality at one year. AB - In this study newly diagnosed male and female lung cancer patients admitted to two Ontario Cancer Foundation treatment clinics were interviewed. Information was obtained on demographic variables, presence of other chronic illness and the following psychosocial attributes: locus of control, social support and personality traits. From the clinic charts, information on stage of disease and pathological diagnosis was obtained. After controlling for the effects of stage and pathological diagnosis, the following psychological variables were found to increase the odds of death from lung cancer among males and females combined at one year after diagnosis: a high need for one aspect of social support, a reserved personality and the extremes of the personality trait soberness vs enthusiasm. PMID- 3335873 TI - Physical status score and trends in anesthetic complications. AB - Since deaths due to anesthesia have now become rare, emphasis in quality assurance of anesthetic care must focus on morbidity rather than only on mortality. To facilitate comparisons of outcomes, data from a large anesthesia follow-up program (N = 112,000 anesthetics) were used to evaluate the usefulness of the American Society of Anesthesiologists' Physical Status score (PS) as an independent predictor of nonfatal adverse anesthetic complications. For each patient, the anesthesiologist filled out a form containing information about the patient, the anesthetic, the operative procedure, and outcomes in the operating and recovery rooms. Postoperative complications were assessed by a designated anesthesia follow-up nurse. We calculated the PS-specific complication rate by dividing the number of complications to patients in each PS category by the number of anesthetics given to patients in the same category. We found that PS specific complication rates increased with increasing PS scores for most complications sought. For intraoperative and recovery room complications, the PS specific rates increased from 1978-80 and 1981-83 as compared to 1975-77. However, there was no increase over time in the rate of postoperative major complications. After adjusting for patient, anesthesia, and surgery-related variables by multiple logistic regression, the relative odds of having an intraoperative or postoperative major complication were increased for patients classified PS2, PS3 and PS4 & 5 as compared to PS1. However, those in higher PS categories were less likely to have a recovery room complication than PS1 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335874 TI - Serum cholesterol and colorectal polyps. AB - Colorectal cancer and hypocholesterolemia have recently been associated, and colorectal polyps have a known relationship with colorectal cancer. In order to establish further evidence regarding the nature of the serum cholesterol colorectal cancer relationship, this study investigated the hypothesis that men with colorectal polyps would have lower serum cholesterol levels than men without polyps. Of the 1380 men screened by sigmoidoscopy for colorectal polyps, 246 had at least one polyp. The men with polyps were older than those without, and also had higher cholesterol levels, but after controlling for age, there were no serum cholesterol differences. These data suggest that low serum cholesterol is not etiologically linked to cancer. Analyses of potentially confounding variables showed smoking to be strongly related to the presence of polyps. PMID- 3335875 TI - Familial aggregation of congenital dislocation of the hip in a Norwegian population. AB - Previous studies of congenital dislocation of the hip have not used adequate control groups in estimating the level of genetic influence on that trait. Furthermore, it could not be demonstrated that alleged maternal effects were not an artifact of reporting bias. To that end, information was obtained on the presence of the anomaly in the families of adult twins and their spouses participating in the Norwegian Twin Registry. The prevalence odds ratio for having that disorder in first degree relatives was 10.0. Stratifying by class of relatives, the prevalence odds ratio was 8.1 for fathers, 35.8 for mothers, 12.7 for siblings, and 3.3 for offspring. The increased prevalence odds ratio for mothers over that of fathers suggests a maternal effect. Since both males and females reported on the anomaly for each parental type, it is unlikely that the difference in prevalence odds ratios is due to general reporting bias. PMID- 3335876 TI - The sensual physician. PMID- 3335877 TI - The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators. AB - A World Health Organization Working Group has developed a major international collaborative study with the objective of measuring over 10 years, and in many different populations, the trends in, and determinants of, cardiovascular disease. Specifically the programme focuses on trends in event rates for validated fatal and non-fatal coronary heart attacks and strokes, and on trends in cardiovascular risk factors (blood pressure, cigarette smoking and serum cholesterol) in men and women aged 25-64 in the same defined communities. By this means it is hoped both to measure changes in cardiovascular mortality and to see how far they are explained; on the one hand by changes in incidence mediated by risk factor levels; and on the other by changes in case-fatality rates, related to medical care. Population centres need to be large and numerous; to reliably establish 10-year trends in event rates within a centre 200 or more fatal events in men per year are needed, while for the collaborative study a multiplicity of internally homogeneous centres showing differing trends will provide the best test of the hypotheses. Forty-one MONICA Collaborating Centres, using a standardized protocol, are studying 118 Reporting Units (subpopulations) with a total population aged 25-64 (both sexes) of about 15 million. PMID- 3335878 TI - Dementia in medical wards. AB - Patients aged 65 years and over admitted to one Department of Medicine in a University Hospital were evaluated for the frequency and types of dementia, and for the greater workload caused by the demented patients to the hospital. The frequency of moderate and severe dementia among consecutively admitted medical inpatients (N = 282) of all age groups was 12.1%. In the age-group 65-69 years it was 5.7%, and among the patients aged 80 and over 20.7%. Of all the patients at the wards in a one-day sample (N = 85), 40% were moderately or severely demented. Patients with vascular dementia constituted 69.4%, those with primary degenerative dementia 16.1%, and those with dementia due to specific causes 14.5% of all demented patients. The demented patients needed more daily nursing care and their mean hospitalization time was longer than that of the non-demented patients. PMID- 3335879 TI - Internal Consistency Analysis: a method for studying the accuracy of function assessment for health outcome and quality of life evaluation. AB - Social, mental and physical function are major components of health outcomes and health related life quality, but the accuracy of function measurement is difficult to study rigorously. Internal Consistency Analysis (ICA) uses multiple sources of evidence from a survey interview to study the accuracy of a classification. It was developed to study function classifications for a general health outcome measure, the Quality of Well-being (QWB) scale. ICA is described and evidence of its utility in improving the classifications needed for the QWB is presented. PMID- 3335880 TI - A prospective study of psychological and socioeconomic characteristics, health behavior and morbidity in cigarette smokers prior to quitting compared to persistent smokers and non-smokers. AB - Psychosocial factors influencing smoking cessation were studied in current smokers prior to quitting. Two questionnaires were sent in 1975 and 1981 to adult members of the Finnish Twin Cohort. The 1975 response rate was 89%, and 89% of those eligible replied again in 1981. Analysis was done on data from one twin pair member only. Three groups were identified: 3617 never smokers, 2654 persistent smokers, and 823 quitters (i.e. current smokers in 1975, former smokers in 1981). Univariate and multivariate comparisons of baseline psychosocial variables for quitters and persistent smokers were performed in men aged 20-34 and 35-54 and women aged 20-39. Among women and young men quitters were better educated and scored lower on neuroticism. Young male quitters also slept longer, had been less often unemployed and drank less alcohol and coffee. Among middle-aged men quitters were more often married, slept longer, and had higher life satisfaction. The possibility that the influence of psychosocial factors on chronic disease may be mediated in part through changes in smoking behavior is discussed. PMID- 3335881 TI - The contribution of a non-invasive test to clinical care. The impact of echocardiography on diagnosis, management and patient anxiety. AB - We prospectively studied the impact of echocardiography on a cardiologist's diagnosis and management plan and on patient anxiety for 300 consecutive referrals. There was an impact on diagnosis in 90% of patients. Most common was confirmation of diagnosis usually with the addition of information pertinent to management (81%); change of disease category or resolution of diagnostic doubt was uncommon (9%). The consultant cardiologist believed the heart to be normal in 48 patients who did not have any associated disease; none had any echocardiographic abnormality. The cardiologist reported increased diagnostic confidence in 74% of all patients but management changed in only 9%. One-third of all patients reported reduced anxiety when this was an important clinical issue but in less than half of them did the cardiologist consider that echocardiographic information was essential for reassurance. Anxiety was increased in 6%, and in 12% the anxiety response was inconsistent with the test result. The clinical contribution of the test report was most obvious for those patients (30%) in whom this data was required for (a) a decision concerning specific diagnostic or technical intervention (b) a change of management plan which implied obvious or likely health benefit (c) reassurance which was a clinically important issue. The magnitude of this contribution was related to the study indication. The value of echocardiography is obvious when assessing patients for invasive intervention or when proper treatment or adequate reassurance are impeded by diagnostic doubt. However, for many current indications, we need better definition of factors which predict a clinically useful result. In particular, when the aim is to rule-out disease, our results suggest that an expert cardiological opinion would often be more appropriate than an echocardiogram. PMID- 3335882 TI - Spinal cord injury rehabilitation outcome: the impact of age. AB - The effect of age on self-care and mobility skill performance after spinal cord injury was studied using a 15-task modified Barthel Index (MBI) to score functional abilities for 708 patients aged 6 through 88 years. Analysis of covariance showed no relationship between age and discharge MBI score; however, patients with paraplegia, incomplete lesions, and greater admission functional ratings had greater discharge functional scores than did those with quadriplegia, complete lesions, and lower admission scores, respectively. Advancing age was associated with increased dependence in only seven functional skills (bathing, upper and lower body dressing, stair climbing, and transfers to chair, toilet and bath) and only for patients with complete paraplegia. Other MBI component tasks and patients with complete quadriplegia, incomplete paraplegia and incomplete quadriplegia demonstrated no relationship between age and skill performance. Results of this study support the practice of providing comprehensive rehabilitation services to all patients following spinal cord injury regardless of age. PMID- 3335883 TI - U.S. lung cancer mortality and declining cigarette tobacco consumption. AB - The usual method for estimating population exposure to cigarette tobacco has been annual per capita consumption of cigarettes, expressed as pack-years or numbers of cigarettes consumed. This technique is shown to result in an inaccurate estimate of exposure. It underestimates by 11 years the latency period from peak exposure to peak mortality. Over the years, cigarettes changed markedly. Filters came into prominence and tobacco was "fluffed". On average, tobacco content of cigarettes decreased 39.1% from 1953 to 1981. National per capita consumption of cigarette tobacco declined by 43%. Total exposure to cigarette tobacco has been declining for males for approximately 35 years; for females for 20 years. As of 1982, the secular trend for lung cancer mortality was declining for women below age 45 and for most age groups of men below 65. We appear to be at the threshold of a reversal in overall lung cancer mortality. PMID- 3335884 TI - Referral bias in multiple sclerosis research. AB - Referral bias is a significant problem affecting the generalizability of clinical studies conducted in a university setting. To examine referral bias in our university-based multiple sclerosis referral center, we analyzed the characteristics of referral center patients compared to the population-based group of multiple sclerosis patients from which the referral center patients originated. The referral center patient group differed from those that remained in the population-based group in the following important ways: (1) they were younger, (2) they had more mobility impairment for their age, (3) disabled females were overrepresented compared to disabled males, (4) they more often reported recent disease worsening, (5) they had a higher frequency of early diagnosis supported by laboratory tests, and (6) they more often relied on neurologists and therapists for routine care of their disease. The multiple sclerosis referral center setting would appear to be ideal for the conduct of intervention trials, but inadequate for collecting representative natural history data. PMID- 3335885 TI - Interactions and public health decisions. PMID- 3335887 TI - Clinical usefulness of an algorithm for the early diagnosis of spinal metastatic disease. AB - We have previously reported an algorithm that invokes several imaging modalities in the early detection of metastatic and benign disease of the spine in patients with cancer (J Clin Oncol 4:576, 1986). The development of new lesions (shown by Tc99m bone scans) in cancer patients with normal neurological examinations is further evaluated with plain radiographs, spinal computed tomography (CT), and CT myelography (CT-M). Of 60 patients in the original study, 28% were diagnosed as having only benign disease and the remainder had spinal metastases. Thecal sac impingement was seen in 47% of patients with metastatic disease and disruption of the posterior vertebral cortex was noted in all patients with epidural compression. We now report the 2-year follow-up of 55 of these patients. Without treatment, the 17 patients diagnosed with benign disease have shown no evidence of local failure in the spine and median survival is greater than 27 months. Thirty-eight patients diagnosed with spinal metastases had a median survival time of 16.9 months. Radiation therapy directed by CT-M findings provided pain relief in 78% of patients with back pain and metastatic disease. No patient, including 19 with thecal sac impingement, developed clinical myelopathy. These results demonstrate the usefulness of an imaging algorithm for the early identification and distinction of spinal metastatic disease and benign disease in patients with cancer. PMID- 3335886 TI - Malignant mesothelioma: prognostic variables in a registry of 180 patients, the Dana-Farber Cancer Institute and Brigham and Women's Hospital experience over two decades, 1965-1985. AB - All mesothelioma patients identified by a computer search of pathologic diagnoses at the Dana-Farber Cancer Institute (DFCI) between 1965 and 1985 were the subjects of this analysis. A total of 180 patients were identified, 136 with pleural and 37 with peritoneal mesothelioma. There were five pericardial and two testicular primaries. Of the two decades included in the study, later patients were significantly older, with a more advanced disease stage, and a lower performance status than those accrued early in the study. Factors at diagnosis associated with a significantly prolonged survival for all patients with mesothelioma included a 0 to 1 performance status, absence of chest pain, age less than 50 years, and epithelial histology. Factors at diagnosis associated with prolonged survival for the subset of patients with pleural mesothelioma included epithelial histology, 0 to 1 performance status, the absence of chest pain, an interval of greater than 6 months from onset of symptoms, and treatment with chemotherapy and pleuropneumonectomy. This last result must be interpreted with caution, since this was not a randomized study. PMID- 3335889 TI - Adhesive tumor cell culture system. PMID- 3335888 TI - Phase I trial of concurrent intraperitoneal and continuous intravenous infusion of fluorouracil in patients with refractory cancer. AB - In an effort to maximize both local-regional and systemic drug exposure to tumor in the peritoneal cavity, a phase I study was conducted that examined the simultaneous daily intraperitoneal (IP) and continuous intravenous infusion (CVI) of fluorouracil (5-FU) to 32 patients with refractory cancer. IP 5-FU administered at 1,000 mg/d with concurrent 5-FU by CVI at 1,000 mg/m2/d for four consecutive days was well tolerated. One patient with a primary gastrointestinal (GI) malignancy with minimal volume disease experienced a surgically defined complete remission. In theory, this regimen may demonstrate clinical utility as an adjuvant treatment of certain GI malignancies. Future studies are planned in this clinical setting. PMID- 3335890 TI - Staging for pediatric patients with Hodgkin's disease. PMID- 3335891 TI - Chemotherapy of soft tissue sarcomas. PMID- 3335892 TI - Very-high-dose cisplatin and etoposide in children with untreated advanced neuroblastoma. AB - Between January and December 1985, 17 children with advanced neuroblastoma who were greater than 1 year old (16 stage IV, one stage III) were administered cisplatin (CPDD, 200 mg/m2) and etoposide (VP-16, 500 mg/m2) as a pilot study of toxicity and response rates for the European Neuroblastoma Study Group (ENSG). The study was designed to assess toxicity of two courses of treatment, and evaluate response rates after this short therapy. The creatinine clearance declined in seven of 15 patients. No patient experienced clinically significant hearing loss, but formal audiometric assessment of nine children revealed characteristic high tone loss in seven patients. Peripheral neuropathy was not seen. Asymptomatic hypomagnesemia (less than 0.7 microEq/L) was frequent, despite routine supplementation. Asymptomatic electrolyte imbalances occurred frequently, but were generally transient. Myelosuppression was severe, but brief. Seven patients required platelet transfusions and seven were readmitted between courses due to febrile episodes while neutropenic. There were no treatment-related deaths. According to strictly defined criteria, 12 of 17 patients showed a partial response (PR), and extensive marrow evaluation showed complete clearing of disease in six of 15 patients. This high-dose regimen, if carefully supervised, is associated with acceptable toxicity, comparable to that seen when the dose of CPDD is spread over several months. The rapidity and degree of response was encouraging and merits further evaluation. PMID- 3335893 TI - Cyclophosphamide-induced hemorrhagic cystitis in Ewing's sarcoma. AB - Recent improvements in survival of patients with Ewing's sarcoma have been made since the addition of cyclophosphamide-based adjuvant chemotherapy to primary surgery and radiation. A potential limitation to cyclophosphamide use is its urotoxicity, primarily in the form of hemorrhagic cystitis. The incidence of this adverse effect in patients treated for Ewing's sarcoma has not been established. In a Mayo Clinic series of 116 patients with Ewing's sarcoma treated with cyclophosphamide, 17 (15%) developed hemorrhagic cystitis diagnosed on the basis of gross hematuria or cystoscopic findings (or both). Microscopic hematuria also occurred in 53% of patients (56 of 105 examined). The dose and duration of therapy appeared to be unrelated to the development of urotoxicity. Most patients recovered uneventfully with or without discontinuation of cyclophosphamide therapy, but a significant loss of blood occurred in three patients, and one patient required a cystectomy because of bladder fibrosis. Long-term follow-up is mandatory in these patients because of late recurrences of hemorrhagic cystitis or the possibility of bladder carcinoma. New therapies, directed at protecting the bladder from urotoxicity during cyclophosphamide treatment, are available. PMID- 3335894 TI - Node-negative breast cancer treated by modified radical mastectomy without adjuvant therapies: variables associated with disease recurrence and survivorship. AB - The present study attempts to identify poor prognosis subgroups of women with node-negative breast cancer that might benefit from systemic adjuvant therapy. The cases were collected through a cooperative effort of 57 surgeons at eight hospitals in the Detroit area and coordinated by the Michigan Cancer Foundation where data collection and analyses were completed. The primary treatment of all patients was a modified radical mastectomy. Of the 1,078 cases accessioned between October 1975 and April 1983, 537 were found to have no microscopic lymph node involvement and 462 of these cases received no adjuvant antineoplastic therapy. The period of follow-up of these cases (alive, n = 358) has been 78.75 +/- 24.6 months (mean +/- SD). Overall, the cumulative 6-year recurrence rate as calculated by life table analysis was 26%, with 16.8% dying of their disease. Tumor size was an important prognostic factor; the recurrence rate was 16.2% for those with primaries measuring less than or equal to 1 cm, with only a 6.3% mortality. Patients with tumors measuring greater than 5 cm also did well: 13.7% recurrence and 13.7% mortality rates at 6 years. The premenopausal women did slightly, but not statistically significantly, better than those who were postmenopausal. The presence or absence of quantifiable estrogen receptor protein (ER) was of little predictive value as far as rates of recurrence were concerned, but patients with an ER-positive tumor survived significantly longer. In postmenopausal women, those whose tumor lacked ER (n = 112) fared poorly: 30.4% experienced a recurrence by 6 years and 28% died of their disease. Recurrence rates and death rates were also high in a small group (n = 35) of postmenopausal women with ER+ tumors exhibiting nuclear pleomorphism (nuclear grade [NG]3) (38% and 24.3%, respectively). No poor prognosis group of premenopausal women was identified. PMID- 3335896 TI - Evaluation of acellular and cellular nerve grafts in repair of rat peripheral nerve. AB - Nerve grafts composed of basal lamina scaffolds and lacking viable Schwann cells have recently been shown to be effective in supporting axonal regeneration. As only short grafts were used in those studies, the present investigation was conducted to evaluate the ability of long acellular basal lamina nerve grafts and equivalent cellular grafts to support axonal regeneration for nerve gap repair. Cellular grafts consisted of nerve segments that had degenerated in situ for 4 weeks. Acellular grafting material consisted of similar segments that were repeatedly frozen and thawed to kill all cells prior to grafting. The results show that host axons can regenerate through the entire 4-cm length of cellular grafts but not through acellular basal lamina grafts. However, in the acellular grafts numerous axons were seen in the proximal 2-cm region. It is concluded that basal lamina grafts possess limited ability to support axonal regeneration. As in cellular grafts, viable Schwann cells appear to be important for regeneration to occur over longer distances. PMID- 3335895 TI - Phase II study of iproplatin in advanced ovarian carcinoma. AB - Iproplatin (cis-dichloro-trans dihydroxy-bis-isopropyl-amine platinum [IV]; CHIP) was administered intravenously (IV) at monthly intervals at doses of 300 mg/m2 and 240 mg/m2 to ten previously untreated and 97 previously treated patients with advanced ovarian carcinoma. The overall response rate was 78% among patients with no prior chemotherapy, 42% among patients with prior chemotherapy not including cisplatin, and 22% among patients with prior chemotherapy including cisplatin. Overall response rates to iproplatin were 6.4% and 54% in patients with/without clinical evidence of tumor resistance to cisplatin. Thrombocytopenia was the dose limiting toxicity, median time to nadir and to recovery being 2 and 4 weeks, respectively. Patients who had received prior chemotherapy regimens for greater than 1 year showed a 10% greater reduction in platelet count (mean platelet nadir +/- SD, 57.5 +/- 49.96 X 10(3)/microL) and a higher incidence of grade 3 to 4 thrombocytopenia after the first cycle than patients who had received prior chemotherapy regimens for less than 1 year (94.7 +/- 65.99 X 10(3)/microL) Moderate to severe vomiting and diarrhea occurred in 84% and 16% of patients pretreated with chemotherapy. Neuropathy (6%) was reported only in patients with prior cisplatin treatment. Mild and reversible renal toxicity was observed in 6% of cases. Iproplatin is an active drug in ovarian cancer; the results achieved in patients previously treated with cisplatin strongly suggest that the two drugs are cross-resistant. PMID- 3335897 TI - Retrograde degeneration of corticospinal axons following transection of the spinal cord in rats. A quantitative study with anterogradely transported horseradish peroxidase. AB - The extent of the retrograde degeneration of corticospinal axons following transection of the spinal cord was studied in rats by labeling corticospinal axons with anterogradely transported horseradish peroxidase injected in the sensorimotor cortex. Axotomized corticospinal axons underwent progressive and continuing retrograde degeneration. In specimens examined 5, 14, 28, and 56 days after trauma, the tips of the transected corticospinal axons were seen to terminate at 181 +/- 80 microns, 977 +/- 203 microns, 1751 +/- 344 microns, and 2559 +/- 466 microns (mean +/- standard deviation), respectively, from the site of transection. The rate of retrograde degeneration varied according to the interval after spinal cord transection, as follows: 36.2 microns/day during the first 5 days; 88.4 microns/day between 5 and 14 days; 55.3 microns/day between 14 and 28 days; and 28.8 microns/day between 28 and 56 days. These findings may serve as useful parameters for the objective assessment of therapeutic modalities in spinal cord injury research. PMID- 3335898 TI - The effects of hypovolemic hypotension on high-energy phosphate metabolism of traumatized brain in rats. AB - To clarify the effect of hypovolemic hypotension on high-energy phosphate metabolism in head injury, sequential changes in in vivo phosphorus-31 magnetic resonance (31P MR) spectra were compared in 35 rats after impact injury with and without hypotension. Fourteen rats were subjected to hypotension alone (mean arterial blood pressure (MABP) of either 40 or 30 mm Hg for 60 minutes), seven to fluid-percussion impact injury (4 to 5 atm) alone, and 14 to impact injury and hypotension (MABP of 40 to 30 mm Hg). Impact injury alone caused a transient decrease in the phosphocreatine (PCr) level and an increase in the inorganic phosphate (Pi) value. While hypotension alone produced only small changes on 31P MR spectra, impact injury plus hypotension caused pronounced changes. Impact injury and an MABP of 40 mm Hg caused a 50% decrease in PCr concentration and an approximately twofold increase in Pi level, which were significantly greater than values in rats with impact injury alone. Impact injury and an MABP of 30 mm Hg also caused a significant decrease in adenosine triphosphate value, which was not observed in rats with impact injury alone or with an MABP of 30 mm Hg alone. Decreases in intracellular pH were greater in rats with impact injury and hypotension. After traumatic injury, the brain is extremely vulnerable to hypovolemic hypotension, as reflected in the loss of high-energy phosphates in brain. PMID- 3335899 TI - The effect of hyperbaric oxygen on glucose utilization in a freeze-traumatized rat brain. AB - Local cerebral glucose utilization was measured with the autoradiographic 2 deoxyglucose technique in rats injured by a focal parietal cortical freeze lesion then treated with hyperbaric oxygen (HBO). The cold lesion depressed glucose utilization in the contralateral as well as in the ipsilateral hemisphere. The largest decreases were observed in ipsilateral cortical areas. Treatment of lesioned animals with HBO at 2 atm for 90 minutes on each of 4 consecutive days tended to increase the overall cerebral glucose utilization measured 5 days after injury when compared to animals exposed to normobaric air. This improvement reached statistical significance in five of the 21 structures studied: the auditory cortex, medial geniculate body, superior olivary nucleus, and lateral geniculate body ipsilateral to the lesion, and the mammillary body. The data indicate that changes in lesioned rats exposed to HBO are not restricted to the period of time that the animals are in the hyperbaric chamber but are persistent. PMID- 3335900 TI - Emergency balloon occlusion for massive epistaxis due to traumatic carotid cavernous aneurysm. Case report. AB - A patient with a giant traumatic aneurysm of the right internal carotid artery presented with recurrent massive epistaxis 30 years after a head injury. During an episode of acute hemorrhage, this patient was effectively treated with occlusion of the internal carotid artery circulation by a detachable inflatable balloon. PMID- 3335901 TI - Intraventricular cryptococcal granuloma. Report of two cases. AB - Infection by Cryptococcus neoformans, a budding nonmycelial yeast, involves the central nervous system in 70% of patients at the time of diagnosis. Meningitis and meningoencephalitis are common manifestations of infection; solid granulomas occur but are unusual, and intraventricular granulomas are distinctly rare. Two cases of intraventricular cryptococcal granuloma are reported. The diagnosis and treatment of mass lesions due to cryptococcal infection are discussed, with special reference to intraventricular granulomas. PMID- 3335902 TI - Rapid resolution of acute epidural hematoma. Report of two cases. AB - Two cases of acute epidural hematoma with rapid resolution followed by a benign clinical course are reported. Because of the concomitant increase in the epicranial hematoma over a linear skull fracture in each case, the acute epidural hematoma was presumed to have been decompressed into the epicranial region through the fracture line. PMID- 3335904 TI - Adrenal medullary tissue transplantation in Parkinson's disease. PMID- 3335905 TI - Direct-implantation model of metastatic and ocular tumors. PMID- 3335906 TI - Thoracic spinal canal stenosis. PMID- 3335903 TI - A new technique for percutaneous study of lumboperitoneal shunt patency. Technical note. AB - A new technique for percutaneous imaging of a one-piece lumboperitoneal shunt is described. Patency of the shunt can be assessed by the intraperitoneal spread of contrast medium which is injected intrathecally via the lumbar route. No special equipment or instrumentation is required other than a typical lumbar puncture tray and a general examination tilt table for fluoroscopy. PMID- 3335907 TI - Pediatric spinal trauma. Review of 122 cases of spinal cord and vertebral column injuries. AB - A review of 122 pediatric cases of vertebral column and spinal cord injuries is presented. These relatively uncommon injuries can be characterized by four distinct injury patterns: fracture only, fracture with subluxation, subluxation only, and spinal cord injury without radiographic abnormality. The immature pediatric spine has several anatomical and biomechanical features that distinguish it from the mature adolescent spine and, accordingly, the frequency of the injury type, the level of spine injury, and the incidence of neurological compromise were found to vary with the age of the patient. Follow-up data were obtained in 93% of the cases (median duration 44 months). No patient was made worse by treatment, 89% of the patients with incomplete myelopathy on admission were improved on their last examination, and 20% of the patients with a complete myelopathy had evidence of significant recovery of function. The authors conclude that the outcome after pediatric spinal trauma is good. PMID- 3335908 TI - Pediatric spinal injury: the very young. AB - Maturity of the spine and spine-supporting structures is an important variable distinguishing spinal cord injuries in children from those in adults. Clinical data are presented from 71 children aged 12 years or younger who constituted 2.7% of 2598 spinal cord-injured patients admitted to the authors' institutions from June, 1972, to June, 1986. The 47 children with traumatic spinal cord injury averaged 6.9 years of age and included 20 girls (43%). The etiology of the pediatric injuries differed from that of adult injuries in that falls were the most common causative factor (38%) followed by automobile-related injuries (20%). Ten children (21.3%) had spinal cord injury without radiographic abnormality (SCIWORA), whereas 27 (57%) had evidence of neurological injury. Complete neurological injury was seen in 19% of all traumatic pediatric spinal cord injuries and in 40% of those with SCIWORA. The most frequent level of spinal injury was C-2 (27%, 15 cases) followed by T-10 (13%, seven cases). Upon statistical examination of the data, a subpopulation of children aged 3 years or younger emerged. These very young children had a significant difference in level of injury, requirement for surgical stability, and sex distribution compared to 4 to 12-year-old children. PMID- 3335909 TI - Cavernous angiomas of the spinal cord. AB - Five cases of histologically verified cavernous angiomas of the spinal cord are reported. Acute lower-extremity sensory disturbance was the initial symptom in four patients, and one presented with weakness of the hand. Progressive neurological deficit occurred in all patients, but the clinical course and outcome were extremely variable. Myelography revealed an intramedullary lesion in two cases but was completely normal in three; magnetic resonance imaging was diagnostic in these patients. Subtotal removal was accomplished in two cases, and myelotomy and biopsy were carried out in three. Four of the cavernous angiomas were located in the cervicothoracic region, whereas one was found in the thoracolumbar cord. All of the patients exhibited characteristic gross and microscopic features as well as hemosiderin-laden macrophages indicating remote hemorrhage. The diagnostic, therapeutic, and prognostic implications of this rare condition are discussed. PMID- 3335911 TI - Recurrences of cerebellar astrocytomas: a violation of Collins' law. AB - Cerebellar astrocytomas generally carry an excellent prognosis when managed with surgical treatment alone. However, these tumors may violate Collins' Law in two opposite ways: by recurring late or by being "cured" with incomplete excision. In a study of 41 cases of cerebellar astrocytoma and a review of the literature, no gross or microscopic factors that correlated with either of these two outcomes could be identified other than brain-stem involvement. The effect of radiation therapy in the treatment of primary or recurrent cerebellar astrocytomas was not detectable when analyzed the same way. Malignant recurrence of cerebellar astrocytoma and primary malignant tumors of the cerebellum are so rare that the possibility should not be taken as a reason to substitute radiation therapy for surgical excision repeated as necessary. PMID- 3335910 TI - Thoracic spinal stenosis: experience with seven cases. AB - The authors report seven cases of thoracic spinal stenosis caused by thickening of the laminar arch and facet joints. Claudication was a prominent clinical feature of this disorder. Motor and sensory abnormalities were found in all cases with either segmental or peripheral distribution. Diagnosis was best made from the computerized tomography scans. Treatment consisted of extensive posterior decompression including medial facetectomy, resulting in satisfactory improvement in five of the seven patients. A review of the literature regarding this disorder is presented. PMID- 3335912 TI - Acute epidural hematoma: an analysis of factors influencing the outcome of patients undergoing surgery in coma. AB - Mortality due to epidural hematoma is virtually restricted to patients who undergo surgery for that condition while in coma. The authors have analyzed the factors influencing the outcome of 64 patients who underwent epidural hematoma evacuation while in coma. These patients represented 41% of the 156 patients operated on for epidural hematoma at their centers after the introduction of computerized tomography (CT). Eighteen patients (28.1%) died, two (3.1%) became severely disabled, and 44 (68.8%) made a functional recovery. The mortality rate for the entire series was 12%, significantly lower than the 30% rate observed when only angiographic studies were available. A significant correlation was found between the final result and the mechanism of injury, the interval between trauma and surgery, the motor score at operation, the hematoma CT density (homogeneous vs. heterogeneous), and the hematoma volume. The patient's age, the course of consciousness before operation (whether there was a lucid interval), and the clot location did not correlate with the final outcome. The mortality rate was significantly higher in patients operated on within 6 hours or between 6 and 12 hours after injury than in those undergoing surgery 12 to 48 hours after injury. Compared with the patients operated on later, the patients undergoing surgery in the early period were, on the average, older and had more rapidly developing symptoms, more pupillary changes, lower motor scores at surgery, larger hematomas, a higher incidence of mixed CT density clots, more severe associated intracranial lesions, and higher postoperative intracranial pressure (ICP). The mechanism of trauma seems to influence the course of consciousness before and after surgery. Passengers injured in traffic accidents had a lower incidence of a lucid interval and longer postoperative coma than patients with low-speed trauma, suggesting more frequent association of diffuse white matter shearing injury. The duration of postoperative coma correlated with the morbidity rate in survivors. Forty-eight patients (75%) had one or more associated intracranial lesions, and 70% of these required treatment for elevation of ICP after hematoma evacuation. An ICP of over 35 mm Hg strongly correlated with poor outcome; administration of high-dose barbiturates was the only effective means for lowering ICP in nine of 15 patients who developed severe intracranial hypertension after surgery. This study attempts to identify patients at greater risk for presenting postoperative complications and to define a strategy for control CT scanning and ICP monitoring. PMID- 3335913 TI - Subdural tension pneumocephalus following surgery for chronic subdural hematoma. AB - The computerized tomography (CT) findings were analyzed in five cases of subdural tension pneumocephalus following surgery for chronic subdural hematoma. They were compared with CT scans in 14 cases of asymptomatic subdural pneumocephalus. In this study, two new CT findings were identified that suggest increased tension of the subdural air. Subdural air separates and compresses the frontal lobes, creating a widened interhemispheric space between the tips of the frontal lobes that mimics the silhouette of Mt. Fuji. The presence of air between the frontal tips associated with massive air inclusion over the frontal lobes presumably indicates increased tension of the subdural air. The "Mt. Fuji sign" was seen in four of the five cases with subdural tension pneumocephalus. The other finding was the presence of multiple small air bubbles scattered through several cisterns ("air bubble sign"). It is postulated that these air bubbles enter the subarachnoid space through a tear in the arachnoid membrane caused by increased tension of air in the subdural space. This finding was seen in four cases with subdural tension pneumocephalus. These two CT findings are helpful in making a diagnosis of subdural tension pneumocephalus following surgery for chronic subdural hematoma. PMID- 3335914 TI - Plasminogen activator activity and molecular weight patterns in human brain tumors. AB - Fresh human brain-tumor samples were assayed for their plasminogen activator (PA) content. Specific molecular weight patterns were identified for each of five common brain tumors and for normal brain, suggesting a cell-specific origin of the various PA forms. Malignant tumors contained higher PA activity and a larger number of molecular weight patterns than benign tumors, with the exception of acoustic neurinomas. Irradiated tumors contained lower PA activity than nonirradiated tumors. Finally, a slight but definite correlation between brain edema and PA activity was detected. The future role of brain-tumor PA's for diagnostic and therapeutic purposes is discussed. PMID- 3335915 TI - Optic nerve decompression in osteopetrosis. AB - Osteopetrosis is a rare disorder characterized by generalized increased skeletal density with abnormalities of bone modeling. The skull base is usually involved. Loss of vision with optic nerve atrophy is the most common neurological finding and is traditionally believed to be the result of optic nerve compression within the compromised optic canal. However, retinal degeneration has recently been described and is hypothesized to be the etiology of the visual loss (thus challenging the value of surgical decompression). The authors report their experience with six children suffering from osteopetrosis and severe visual loss. All six patients underwent bilateral microsurgical optic nerve decompression through a supraorbital craniotomy. Improvement in visual acuity occurred postoperatively in five patients, and none had complications. Two technical points are emphasized: 1) optic nerve decompression should be wide and include not only unroofing of the canal but also drilling along both sides of the optic nerve, and 2) the thick, irregular, and highly domed orbital roof should be smoothed down by high-speed drilling to facilitate surgical exposure with minimal retraction of the frontal lobe. PMID- 3335916 TI - Tumor uptake as a function of tumor mass: a mathematic model. AB - Inverse correlations of tumor uptake (u), measured in percent injected dose per gram, with tumor mass (m) are demonstrated for phospholipid vesicle, nonspecific and specific monoclonal antibody tracers. Correlation coefficients implied u = B mA in 11 different animal experiments. Experimental exponent (A) values lay in the range -0.28-0.64 with a mean of -0.43 while intercept (B) values varied from 3 to 18. Spherical and cylindrical tumor models implied exponents of -0.33 and 0.5, respectively. Comparison of three implantation sites of the human LS174T xenograft revealed a narrow range of exponents (-0.38- -0.46) indicating a consistent geometry for this tumor. Blood flow to the lesion site and inside its volume (as dictated by tumor size) are factors in tumor uptake. Our results indicate that biodistribution data should include the variation of tumor uptake with mass. For less than 10 g lesions, we predict that radiation absorbed dose will be highly dependent upon tumor size. PMID- 3335918 TI - Ventilation-perfusion scan in the acutely ill patient with unilateral hyperlucent lung. AB - A patient with a unilateral hyperlucent lung with acute respiratory complaints is presented. A ventilation-perfusion scan was performed to rule out pulmonary embolism. The perfusion scan ( [99mTC]MAA) showed peripheral perfusion defects in the hyperlucent lung. The ventilation study (133Xe) demonstrated peripheral ventilatory defects on the single breath image in the hyperlucent lung, the filling in of these on the equilibrium view, and diffusely delayed washout in the affected lung. These findings were suggestive of the Swyer-James syndrome and critical in excluding the numerous other causes of unilateral hyperlucent lung, which are discussed. The importance of the ventilation-perfusion study (and particularly the ventilation scan) in the patient with unilateral hyperlucent lung and acute respiratory symptoms is stressed. In addition, a discussion of the Swyer-James syndrome is included. PMID- 3335917 TI - Carbon-14 urea breath test for the diagnosis of Campylobacter pylori associated gastritis. AB - Urease in the human gastric mucosa is a marker for infection with Campylobacter pylori (CP), an organism suspected of causing chronic gastritis and peptic ulceration. To detect gastric urease, we examined 32 patients who were being evaluated for possible peptic ulcer disease. Fasting patients were given 10 microCi (370 kBq) of 14C-labeled urea. Breath samples were collected in hyamine at intervals between 1 and 30 min. The amount of 14C collected at these times was expressed as: body weight X (% of administered dose of 14C in sample)/(mmol of CO2 collected). The presence of C. pylori colonization was also determined by examination of multiple endoscopic gastric biopsy specimens. On average, patients who were proven to have C. pylori infection exhaled 20 times more labeled CO2 than patients who were not infected. The difference between infected patients and C. pylori negative "control" patients was highly significant at all time points between 2 and 30 min after ingestion of the radionuclide (p less than 0.0001). The noninvasive urea breath is less expensive than endoscopic biopsy of the stomach and more accurate than serology as a means of detecting Campylobacter pylori infection. Because the test detects actual viable CP organisms, it can be used to confirm eradication of the bacterium after antibacterial therapy. PMID- 3335920 TI - Bone density measurements of spine and distal forearm in osteoporosis. PMID- 3335919 TI - In vivo chemistry of iofetamine HCl iodine-123 (IMP). AB - Application of chemical methods for characterizing the in vivo behavior of iofetamine HCI 123I (IMP) has shed light on the metabolism of iofetamine in animals and humans. A successful technique consists of ethyl acetate extraction of the metabolites from tissue samples acidified with perchloric acid, separation of the mixture by high performance liquid chromatography, and quantitation of the radioactive components with a sensitive scintillation detector. Metabolism of iofetamine HCI 123I proceeds sequentially from the N-isopropyl group on the amphetamine side chain. The first step, dealkylation to the primary amine p iodoamphetamine (PIA), occurs readily in the brain, lungs, and liver; activity in the brain and lungs consists of only IMP and PIA even 24 hr after administration. The rate-limiting step appears to be deamination to give the transitory intermediate p-iodophenylacetone, which is rapidly degraded to p-iodobenzoic acid and conjugated with glycine in the liver to give the end product of metabolism, p iodohippuric acid, which is excreted through the kidneys in the urine. PMID- 3335921 TI - Quantifying intracranial CSF volume using MRI. PMID- 3335922 TI - Caution in the use of volume expansion diuretic renal scan. PMID- 3335923 TI - Scintigraphic study of duodenal-gastric reflux in cases of primary gastropathy, chronic ulcer of the duodenal bulb, and Moynihan's disease. AB - There are several methods for detection of bile in the stomach, but none has proven satisfactory. It appears that the scintigraphic study with quantitation of duodenal-gastric reflux after corrections for the overlap of the stomach by the liver and bowel is more reliable, noninvasive, and physiologic. Fifty-four patients were divided into groups according to their clinical presentation; seven asymptomatic volunteers, 20 patients with duodenal-gastric reflux gastropathy (DRG), 16 patients with recurrent ulcers of the duodenal bulb (RUD), and 11 patients with Moynihan's disease. Each of the 47 dyspeptic patients underwent an endoscopic examination and a scintigraphic study with [99mTc]disofenin for detection and quantitation of duodenal-gastric reflux. Endoscopy revealed the presence of bile in the stomach of 16 out of 20 DRG and four out of 16 RUD, while ten out of 11 patients with Moynihan's disease had clear gastric juice. Most of the DRG cases (15 out of 20) and half of the RUD (eight out of 16) presented reflux greater than 1.5%, while of the 11 Moynhihan, ten presented reflux less than 1.5% and all the asymptomatic volunteer subjects less than 1%. This quantitation method allowed us to perceive clearly the low % of reflux in the "normal asymptomatic" subjects compared with the DRG-type of dyspeptic patients. Among the dyspeptic, the distinction seems more evident between the DRG type and the Moynihan type. Occasionally, the scintigraphic method permits identification of patients with slower gallbladder evacuation (eight out of 47 dyspeptic in our study), adding valuable information for the diagnostic approach to dyspeptic patients. PMID- 3335924 TI - Comparison of purified indium-111 granulocytes and indium-111 mixed leukocytes for imaging of infections. AB - Several methods have been proposed for the separation and labeling of white blood cells for the diagnosis of suspected infection. We retrospectively compared 105 patients imaged with 111In purified granulocytes (GRAN) to 106 patients imaged with 111In mixed leukocytes (MIX). We found that in acute infection the sensitivity of GRAN and MIX were both high and not statistically different. In chronic infections the sensitivities were lower than for acute infections. Again, there was no significant difference between GRAN and MIX with the borderline significant exception of MIX being superior to GRAN in chronic soft tissue infections (p = 0.06). We then had independent observers blindly grade the degree of lesion visualization. We found that delayed images visualized the lesions better than early images (p = 0.0001) and acute infection was better visualized than chronic infection (p = 0.03). We concluded that, in routine clinical practice, MIX is probably the agent of choice for three reasons: (a) easier preparation, (b) comparable sensitivity in acute infection and, (c) borderline superior sensitivity in chronic infection. PMID- 3335925 TI - Three-phase bone scanning in reflex sympathetic dystrophy of the hand. AB - Three-phase bone scanning was performed in 181 patients suffering from reflex sympathetic dystrophy (RSD) of the hand. Four quantitative parameters were defined as follows: (a) hemovelocity and (b) blood pool (determined from the Fourier processing of angiographic data); (c) early (3-5 min) and (d) delayed (2 3 hr) bone fixation. Three significant stages of RSD were demonstrated scintigraphically. Stage I (0-20 wk from onset) demonstrated increases in velocity, blood pool, and early and delayed fixations. At stage II (20-60 wk) blood velocity and blood pool were normalized, but early and delayed hyperfixation persisted. During stage III (60-100 wk) blood velocity and blood pool were reduced on the affected hand, and early and delayed fixations were normalized. Such abnormality of decreased hemodynamic parameters may become associated with bone hypofixation in stage III. Early treatment of RSD (as compared with delayed treatment) has been demonstrated to induce normalization of hemovelocity (p less than 0.05), blood pool (p less than 0.02), and joint stiffness (p less than 0.001) without any change in the bone fixation; therefore, three-phase bone scanning may provide useful information regarding the pathophysiologic and clinical evolution of RSD. PMID- 3335926 TI - Effect of antibody dose on the imaging and biodistribution of indium-111 9.2.27 anti-melanoma monoclonal antibody. AB - Eleven patients with metastatic melanoma underwent serial gamma camera imaging and biodistribution measurements after i.v. injection of escalating doses of [111In]9.2.27, an antimelanoma murine monoclonal antibody. Patients received a fixed dose of 1 mg of [111In]9.2.27, with no additional 9.2.27 (five patients), or co-infused with 49 mg (five patients) or 99 mg (one patient) of unlabeled, unconjugated 9.2.27. Higher doses resulted in prolonged blood-pool retention, less uptake in spleen and bone marrow, and appeared to have a positive effect in improving tumor imaging. A dose of 1 mg of 9.2.27 permitted detection of tumors in two of five patients and two of ten lesions, while with greater than or equal to 50 mg, tumors were detected in all patients and in 24 of 32 lesions. Human gamma globulin injected prior to administration of [111In]9.2.27 failed to block the prominent liver, spleen, and bone marrow uptake. No toxicity was observed. These results indicate the feasibility of imaging metastatic melanoma with [111In]9.2.27 and suggest that antibody dose may be a critical determinant of biodistribution and tumor uptake. PMID- 3335927 TI - Hexakis (2-methoxy isobutylisonitrile) technetium-99m and thallium-201 chloride: uptake and release in cultured myocardial cells. AB - Hexakis (2-methoxy isobutylisonitrile) technetium-99m [(99mTc]MIBI), a new tracer of myocardial blood flow, was compared with 201TI CI in cultures of myocardial cells of newborn rats. The kinetics of uptake and release of both tracers were assessed in basal conditions and in the presence of 5 mM cyanide, an inhibitor of the respiratory chain, 0.1 mM iodoacetate, an inhibitor of glycolysis, 10 microM ouabain, an inhibitor of the Na-K ATPase, or with various pH values. The amplitude and frequency of contractions of the cells were also monitored in the same conditions. Results show that the washin and washout kinetics of [99mTc]MIBI are slower than 201TI(T1/2) of the washout curves were, respectively, of 28 min and 6 min). The kinetics of release of both tracers were not influenced by any of the inhibitors. There was a strong effect of the pH on the 201TI uptake only. Moreover 201TI uptake was decreased by 34% in the presence of cyanide plus iodoacetate. Otherwise the uptakes of 201TI and [99mTc]MIBI were not decreased by any of the drugs. The cellular contractility was significantly diminished by cyanide and it was abolished by cyanide plus iodoacetate. It is concluded that (a) impaired contractility can be associated with normal 201TI and [99mTc]MIBI kinetics in myocardial cells in culture, (b) that 201TI uptake may depend on the level of ATP devoted to the maintenance of membrane integrity, (c) that [99mTc]MIBI shows slower kinetics but is less sensitive to metabolic inhibitors than 201TI. PMID- 3335928 TI - Hexakis(carbomethoxyisopropylisonitrile) technetium(I), a new myocardial perfusion imaging agent: binding characteristics in cultured chick heart cells. AB - Cellular kinetics and binding characteristics of hexakis(carbomethoxyisopropylisonitrile) technetium(I) (Tc-CPI), a new cationic, highly lipophilic myocardial perfusion imaging agent, were evaluated in chick embryo heart cells grown in monolayer culture. Myocytes showed uptake of Tc-CPI to a plateau level with a half-time (t1/2) of 4.1 +/- 0.7 min (mean +/- s.e.m.; n = 6); t1/2 appeared independent of extracellular Tc-CPI concentration. Plateau level Tc-CPI uptakes (10(-16) to 10(-11) mole Tc-CPI/mg cell protein) were a linear function of extracellular Tc-CPI concentration (range: 10(-13)M to 10( 8)M, respectively). Tracer 99mTc-CPI uptake (binding) was not competitively displaced by carrier 99Tc-CPI. Uptake was temperature-sensitive; however, several inhibitors of cationic membrane transport (ouabain, amiloride, bumetanide, and verapamil) showed no significant effect. Extreme alkalinization of external load solution (pHo approximately 8.5) partially inhibited Tc-CPI uptake; however, intracellular pH changes showed no effect. Washout from contractile preparations could be described by a two component system: a fast component (myocytes) with a t1/2 approximately 4.5 min and a slow component (fibroblasts) with a t1/2 approximately 40 min. Cell fractionation experiments showed most of the activity to be associated with the cell membrane fraction. The data do not demonstrate a specific mechanism for uptake of Tc-CPI; however, results suggest binding to myocytes in a manner proportional to the delivery of the complex to the extracellular spaces. Such properties would be desirable for a myocardial perfusion imaging agent. PMID- 3335929 TI - Protein binding studies of technetium-99m-labeled phosphine and isocyanide cationic complexes. AB - Most 99mTc/phosphine/isocyanide complexes synthesized to date show preferential uptake by the myocardium of many animal species but not in man. A new complex has been synthesized, [99mTc(DEPE)2(CNR)2], +(DEPIC), where R = t - butyl isocyanide, which in three animal species images the myocardium very well, but in humans it remains primarily in the blood pool. One reason for the difference in the behavior of these complexes in different species could be the characteristics of their binding to plasma proteins. The protein binding characteristics of DEPIC and two other well-known complexes have therefore been studied. Whereas the other complexes bind nonspecifically to many proteins both in animal and human plasma, DEPIC binds almost exclusively to prealbumin in humans but nonspecifically to other proteins in the rabbit. The binding sites in human plasma appear to be those normally occupied by thyroxine on the prealbumin tetramer and these can be blocked by sodium salicylate. PMID- 3335930 TI - Synthesis and biologic evaluation of 1-[11C]-3,3-dimethylheptadecanoic acid. AB - 1-[11C]-3,3-dimethylheptadecanoic acid [( 11C]DMHDA) has been prepared for evaluation as a potential myocardial metabolism indicator based on an expected intrinsic stability toward beta-oxidative metabolic processes. Synthesis of this novel branched-chain fatty acid was accomplished by copper-catalyzed addition of tetradecylmagnesium bromide to diethylisopropylidenemalonate. Subsequent saponification and decarboxylation afforded 3,3-dimethylheptadecanoic acid (DMHDA) that was converted to the corresponding alkyl bromide by means of a modified Hunsdiecker reaction. Carboxylation of 2,2-dimethylhexadecylmagnesium bromide with 11CO2 gave [11C]DMHDA. Carbon-11 DMHDA showed moderate myocardial uptake in fasted rats, albeit lower than that reported for the 3-monomethyl analog. Considerable washout of radioactivity from the heart was also observed over the first 30 min postinjection. Imaging in dogs likewise showed disappointing heart uptake with much higher localization in the lung. These data suggest that gem-dimethyl substitution of the beta-position in long chain fatty acids is not only insufficient for enhanced myocardial uptake and retention, but also, may be deleterious when compared with beta-monomethylation. PMID- 3335931 TI - Migratory patterns of different indium-111 labeled leukocyte populations (chiefly lymphocytes) from control and thymectomized rats. AB - The blood clearance and 24-hr organ distribution of five lymphocyte-rich suspensions harvested from different source organs were compared in the Wistar rat, after labeling with [111In]tropolone and intravenous injection. Peripheral blood lymphocytes (chiefly T cells) had the highest levels in the blood and lymph nodes, a relatively higher level in intestine and a lower level in the spleen than other suspensions. Thymocytes cleared promptly from the blood, accumulated markedly in the liver, moderately in the spleen, but very poorly in other organs, including the thymus. Splenic cells (rich in B cells) sequestered predominantly in the spleen and liver. Splenic cells nonadherent to nylon wool (T-cell enriched) had a relatively high uptake in lymph nodes and marrow. Splenic cells from thymectomized rats (NK cell enriched) localized predominantly in the liver and spleen, and poorly in lymph nodes. We conclude that the source organ for harvesting rat lymphocytes is an important determinant in their localization, as well as other factors such as the techniques of isolation, the toxicity and stability of the radioactive label and the cell radiation dose from internalized radioactivity. PMID- 3335932 TI - Effect of lead and niacin on growth and serotonin metabolism in chicks. AB - Interactions of lead and niacin were studied in growing broiler chicks fed one of four experimental diets from day-old to 3 wk of age. The diets were a low niacin basal diet (LN), the basal diet supplemented with 40 mg of niacin/kg (control), the basal diet supplemented with 2000 mg lead/kg, as lead acetate (LN + Pb) and the basal diet supplemented with both niacin and lead (control + Pb). Growth and feed efficiency were reduced significantly by lead. The lead-associated growth depression was less severe in chicks fed the low niacin diet as indicated by a significant lead X niacin interaction. The relative weights of two brain regions (telencephalon and diencephalon) and the adrenal glands were greater in lead treated chicks than in their nonlead-treated counterparts. Plasma and telencephalon tryptophan were lower in lead-treated chicks than in nonlead treated chicks. Diencephalon tryptophan was lower in chicks fed the LN diet than in chicks fed the control diet. Brain serotonin was lower and 5 hydroxyindoleacetic acid was higher in both brain regions of lead-treated chicks than in nonlead-treated chicks. The data indicate that tryptophan and serotonin metabolism were altered by lead treatment, whereas niacin was without effect. The interaction of lead and niacin on growth does not appear to be related to alterations of serotonin metabolism in the central nervous system. PMID- 3335933 TI - Mineral balance and blood pressure in the young spontaneously hypertensive rat. AB - To evaluate factors that might be related to the pathogenesis of hypertension in spontaneously hypertensive rats (SHR), mineral balance studies were conducted in SHR and control Wistar-Kyoto (WKY) rats at the ages of 9, 13 and 16 wk. During the first balance period, before onset of hypertension, Na, Ca, Mg and P balances were all significantly more positive in SHR than in WKY rats. Percentage of absorbed Na excreted in urine was correlated with the rise in blood pressure of SHR but not of WKY rats during the first 4 wk of the study. At 13 wk balances of all four nutrients still tended to be higher in SHR. During the 16th wk of life, after onset of hypertension, Na, Ca and P balances were similar in SHR and WKY rats, but Mg balance was significantly lower in SHR. The percent urinary excretion of absorbed Na was lower in SHR at 9 wk of age, but after onset of hypertension it was similar to that in WKY rats. Food intake was always greater in SHR, whereas growth during the study was less, and absorption of Ca, Mg and P declined more rapidly with age in SHR than in WKY rats. The data suggest that nutrient malabsorption in SHR, if it occurs at all, is most likely an effect of, rather than a cause of, hypertension. PMID- 3335935 TI - Trypsin inhibitors: potential concern for humans? PMID- 3335934 TI - Effects of ingestion of high protein or excess methionine diets by rats for two years. AB - Eighteen male Wistar rats weighing 230 g (9 wk old) were fed casein diets containing 10% protein (HC), 50% protein (HP) or 10% protein plus 2% DL methionine (MET) for 2 yr. In HC rats, mean body weight was 570 g; the carcass contained 13.5% protein and 37% lipid. The HP-fed rats had a 100 g lower body weight than HC rats due solely to a smaller amount of body lipid. Liver urea concentration and kidney weight were higher in HP rats than in HC rats. The body weight of MET-fed rats was lower than the other two groups and body lipid was only 30% that of HC rats. Histologic examination showed a normal aspect of the thoracic aorta from HC rats, whereas in HP, moderate signs of vascular aging- thicker intima and media with hypertrophy of smooth muscular cells (smc) with collagen enrichment and diffuse fibrosis--were observed. Aortas from MET rats also exhibited thicker intima and media due to smc hypertrophy. Some smc presented degenerative aspects and necrosis; other smc were replaced by chondroid cells and foci of fibrosis, resulting in a loss of the distension capacity of the aorta. Such an advanced stage of vascular aging is not normally found in 2-yr-old rats. PMID- 3335936 TI - Epidemiological studies in nutrition: utility and limitations. PMID- 3335937 TI - Quantitation of the enterohepatic circulation of retinol in the rat. AB - Studies were done to determine whether vitamin A is reabsorbed in the enterohepatic circulation in forms that can be reutilized by the body for vision and reproduction. Micelles containing [11,12(n)-3H]retinol were administered orally to mesenteric lymph duct-cannulated rats. Lymph containing [3H]retinyl esters and small amounts of [3H]retinol and [3H]retinaldehyde was collected from these rats and an aliquot was injected into the jugular vein of a second group of mesenteric lymph duct-cannulated rats. The total radioactivity recovered in 24-h lymph collections from recipient rats was only 1.6% of that injected, and the [3H]retinyl esters, [3H]retinol and [3H]retinaldehyde recovered was only 0.9% of that injected. Thus, the amount of vitamin A recovered in the enterohepatic route in forms that can be reutilized by the body for vision and reproduction appears to be very small. Notable differences were observed in the composition of mesenteric lymph containing newly absorbed vitamin A and mesenteric lymph containing recycled vitamin A. In the former, 87% of the total lymph radioactivity was associated with retinyl esters, 5% with retinol, 3% with retinaldehyde and 5% with unidentified mostly nonpolar compounds. In the latter, only 41% of the total lymph radioactivity was associated with retinyl esters, 12% with retinol, 3% with retinaldehyde and 44% with unidentified mostly polar compounds. PMID- 3335938 TI - Iron metabolism in genetically obese (ob/ob) mice. AB - Several reports in the clinical literature suggest that obese children may be at risk for developing iron deficiency. Here the absorption, retention, tissue distribution and tissue levels of iron were compared in lean (+/?) and obese (ob/ob) C57BL/6J mice to examine the impact of obesity on the iron status of this animal model. Obese mice absorbed and retained approximately twice as much 59Fe as lean mice after receiving a solution containing 1 mumol iron per os. This difference was independent of age, severity of obesity and mass of the gastrointestinal tract. Obese mice fed ad libitum had higher levels of 59Fe in blood and fat pads, but lower amounts of 59Fe in the skeletal-muscular system, than lean mice 6 d after subcutaneous injection of 1 mumol of the metal. At least 30% of carcass 59Fe was present in the liver of obese and lean mice 6 d after injection. Despite significantly lower concentrations of iron in liver and bone, blood hemoglobin and hematocrit were significantly higher in obese mice fed ad libitum than in lean mice at 10 wk of age. Plasma iron and transferrin were not affected by chronic obesity. Although several characteristics of iron metabolism differed in obese and lean mice, the results indicate that ob/ob mice were not iron deficient when fed a diet containing an adequate level of this micronutrient. The increased absorption of iron by obese mice probably represents an adaptive response that is required to supply additional micronutrient for the expanded blood volume in these animals. PMID- 3335940 TI - Site of zinc absorption in dog small intestine. AB - An in vivo intestinal perfusion technique was used to study the absorption of zinc from the duodenum, proximal jejunum and distal ileum of six dogs (group 1). Net absorption of zinc from the duodenum before and after ligation of the common bile duct averaged 596 and 574 ng.min-1.cm-1, respectively. Zinc absorption was greater (P less than 0.01) from the duodenum than from the jejunum (251 ng.min 1.cm-1) or ileum (404 ng.min-1.cm-1). Four other dogs (group 2) experienced perfusion of approximately equal segments of the duodenum (in two animals the common bile duct was ligated, and in another two it was not), proximal jejunum and distal ileum for 4 h. No change in absorption of zinc with time was noted, nor was any difference in absorption by the duodenum with and without ligation of the common bile duct observed. The data indicate that the duodenum has the greatest capacity for zinc absorption, followed by the distal ileum and proximal jejunum, and that pancreatic secretions do not appear to be necessary for adequate zinc absorption in the dog duodenum. PMID- 3335939 TI - Iron, copper and zinc metabolism of rats fed various levels and types of tea. AB - The effects of tea and components in tea on mineral metabolism were investigated in a series of studies. In studies A and B weanling rats were fed diets containing various levels (0, 0.35, 1.17 or 3.50%) of a commercially prepared instant tea and diets containing 0 or 1.17% catechin. In study C anemic rats were fed diets containing 0 or 2.31% desiccated green or black tea infusions for 23 d. In study D rats were fed a diet containing 2.31% desiccated black tea infusions for 16 d, were fed the tea-containing diet in a single meal labeled with 59Fe or were given black tea infusions as their sole fluids. Rats fed diets containing 2.31% green or black tea or given fluid tea had elevated hematocrits but experienced minimal changes in tissue iron levels or in iron absorption; this is counter to conclusions from studies in which iron absorption was monitored indirectly. Ingestion of instant or black tea consistently elevated liver copper levels; this may be part of the mechanism by which hematological variables were affected. Although the green tea contained significant amounts of aluminum, rats fed the tea did not accumulate aluminum in their bones. PMID- 3335942 TI - Nutritional value for young children of grain amaranth and maize-amaranth mixtures: effect of processing. AB - Amaranthus caudatus L. toasted flour, popped grain and flakes were each fed to nine young children as the source of all diet protein and fat and 50% of diet energy, preceded and followed by casein control diets. All provided 6.4-6.7% of energy as protein and 9.3-10.1% as fat. Balances were carried out during the last 6 d of the three 9-d amaranth periods and during the four control periods. Fecal wet and dry weights during amaranth diets were 129-157% of those during casein control diets; fecal energy, fat and carbohydrate from the toasted flour periods were 193, 268 and 256%; from the popped grain 253, 586 and 195%; and from the flakes 225, 356 and 255% of those during casein diets. Apparent N absorptions were 84.1-84.6% of the casein values (P less than 0.001); apparent retentions from toasted, popped and flaked amaranth were 70.9, 65.9 and 59.0% of casein (P less than 0.001). The last of these was significantly lower than the first (P less than 0.05). Fecal fat was much higher (P less than 0.001) from the popped than from the flaked grain and the toasted flour. Toasted flour was then added to maize meal so that amaranth provided 20 or 30% of the protein. Seven young children received diets in which 6.4% of total energy came from one of the above mixes, or from casein, as protein. Soya-cottonseed oils completed 25% lipid energy in all three diets; balance of energy was from sucrose in the experimental diets and from sucrose, corn syrup solids and cornstarch in the casein diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335941 TI - Dietary lactose improves endochondral growth and bone development and mineralization in rats fed a vitamin D-deficient diet. AB - Lactose promotes the intestinal absorption of calcium independent of the vitamin D endocrine system. The purpose of this study was to determine the effect of lactose supplementation on endochondral bone growth, bone development and mineralization in weanling rats fed a vitamin D-deficient diet. Rat pups were weaned from vitamin D-deficient dams and fed a vitamin D-deficient diet containing sucrose as the primary carbohydrate source or a similar diet but containing 20% lactose. After 4 wk, body weights, serum calcium levels and endochondral bone elongation rates in the lactose-fed animals were higher than in rats fed the sucrose diet. In addition, bone weights, bone calcium content, percent bone ash of bone dry weight, percent metaphyseal osseous tissues and bone osteoid content in the lactose-fed rats were different from those in the rats fed the sucrose diet. In all cases the changes in osseous tissues that were observed in the animals fed the lactose-supplemented diet were toward normal values as observed in age-matched animals fed a vitamin D-replete diet. The improvements in bone growth and development due to lactose supplementation occurred independent of the vitamin D endocrine system and are likely the result of improved calcium absorption in the intestine. PMID- 3335944 TI - Repeated pregnancy without lactation: effects on carcass composition and adipose tissue cellularity in rats. AB - Four groups of Sprague-Dawley rats, 200-225 g, were mated. Two groups of rats were killed after 3 wk of nursing eight pups (PL-1) or no lactation (PNL-1). The remaining two groups went through three cycles of pregnancy/lactation (PL-3) or pregnancy/no lactation (PNL-3) and were then killed for carcass composition analysis. Two virgin groups (CON-1, CON-3) served as age controls and were killed at the appropriate time. There was a gradual reduction in food intake from cycle 1 to cycle 3 for all groups. PL-3 rats ingested significantly more food than PNL 3 rats in pregnancies of cycle 2 and cycle 3. At the end of cycle 1, there was no difference in body weight, carcass weight, fat content and fat cell cellularity in parametrial and subcutaneous fat pads between three groups of rats. However, after three cycles, the PL-3 group had significantly reduced carcass fat content because of a significant reduction in fat cell number. Repeated pregnancy followed by no lactation resulted in greater carcass fat content and fat cell number in the subcutaneous pad than observed in lactating rats, although these increases failed to reach significance when compared with virgin controls. Thus lactation may not only be beneficial to the offspring but also enhances maternal weight loss and prevents obesity in multiparous individuals. PMID- 3335943 TI - Response surface analyses of the effects of dietary protein on feeding and growth patterns in mice from weaning to maturity. AB - Responses of food intake, protein intake, gross energy intake and body weight of mice from weaning to maturity to dietary protein level were studied. Thirteen groups of ddY male mice were fed purified diets covering the entire range (0 100%) of protein concentration on a gross energy basis for 68 d. The food intake and body weight data in each group were analyzed by nonlinear regression to obtain values of the six parameters in Parks' feeding and growth equations. These parameters, found as a function of the protein content of diet, were then used to construct the response surfaces of food intake and body weight over the dietary protein versus age space. At every protein level the daily energy intake rose rapidly with age to a plateau at about 7-14 d after weaning and was maintained throughout the experiment. Daily energy intake was independent of the dietary protein content except at very low dietary protein contents. Consequently, from 21 to 89 d of age daily protein intake was directly proportional to dietary protein level. These results imply that mice ate for energy rather than protein when fed diets varying in protein content in the range of 10-80%. Body weight as a function of time after weaning increased to a plateau at every dietary protein level, but the details of the pattern of growth were affected by the dietary protein level. Further, the response surface of body weight versus dietary protein level and age was analyzed to find the protein requirement of mice for maximal growth during a given interval from weaning. PMID- 3335945 TI - Calcium and vitamin D in bone metabolism: analyses of their effects with a short term in vivo bone model in rats. AB - A short-term in vivo system was developed to examine simultaneously bone formation and resorption, and the effects of dietary calcium and vitamin D on these processes. In experiment 1, 25 male Long-Evans rats were each implanted with two gelatin capsules containing mineralized bone (MB) powder subcutaneously in the thorax region. At 4, 6, 8, 10 and 12 d after implantation the acid phosphatase activity (resorption) increased significantly (P less than 0.01), whereas alkaline phosphatase activity (formation) did not change. In experiment 2, both MB and demineralized bone (DB) powder were implanted on contralateral dorsal sites of the thorax in 40 male Long-Evans rats and harvested after 7, 9, 11 and 13 d. Enzyme, mineral and histological assessment indicated bone formation in DB implants with bone resorption in MB implants. In experiment 3, the effects of dietary calcium (0.2 or 1.0%) and vitamin D (cholecalciferol at 300 ng/d or 1,25-dihydroxycholecalciferol [1,25(OH)2D3] at 75 ng/d) were examined using 40 male Long-Evans rats. These rats were implanted with both DB and MB powders and the implants were harvested on d 12. Both low (0.2%) dietary calcium and 1,25(OH)2D3 stimulated resorption of MB implants. Therefore, the physiological processes of bone formation and resorption were mimicked in this system of bone powder implants. Further, dietary calcium and 1,25(OH)2D3 were shown to modulate these processes. PMID- 3335946 TI - Regional variations in human newborn cerebral blood flow. AB - Regional differences in the local cerebral metabolic rate of glucose have been reported in newborn infants. This study was performed to determine if comparable differences exist in neonatal regional cerebral blood flow (rCBF). In 21 infants, rCBF was measured with a modified xenon 133 (133Xe) clearance technique by means of eight extracranial detectors positioned over four homologous regions (frontal, parietal, temporal, and occipital). The rCBF was lowest in the frontal region, higher in the parietal region, and highest in the temporal and occipital regions. Regional differences in rCBF may be caused by regional differences in brain development and function. PMID- 3335947 TI - Hemolysis of blood in intravenous tubing caused by heat. PMID- 3335948 TI - Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome. AB - Forty-six children with steroid-responsive nephrotic syndrome were randomly allocated to receive two different prednisolone regimens for initial therapy. Twenty-nine children (group 1) received an intermittent regimen (60 mg/m2/day for 4 weeks, followed by 40/mg/m2/day on 3 days a week for 4 weeks); 17 children (group 2) had a long-term regimen (60 mg/m2/day for 4 weeks, followed by the same dose on alternate days for 4 weeks and the doses tapered by 10 mg/m2, given on alternate days every 4 weeks for 5 months). There was no difference between the two groups in the regimen used to treat relapses, steroid responsiveness, number of patients with relapses, and frequency of toxic reactions to steroids. However, the number of patients with a relapse within 6 months after initial therapy and the number of those with frequent relapses or steroid dependence were significantly higher in group 1 than in group 2 (P less than 0.05 for both). The data indicate that the long-term tapering regimen appears to be both safe and preferable to the intermittent regimen for initial therapy in children with idiopathic nephrotic syndrome. PMID- 3335950 TI - Comparison of two methods of rapid theophylline testing in clinical practice. PMID- 3335949 TI - Asthma and selective immunoglobulin subclass deficiency: improvement of asthma after immunoglobulin replacement therapy. PMID- 3335951 TI - Cocaine convulsions in a breast-feeding baby. PMID- 3335953 TI - Measuring suck patterns. PMID- 3335954 TI - Diagnostic studies for neonatal cholestasis. PMID- 3335955 TI - Diagnosis of familial dysautonomia in the newborn period. PMID- 3335952 TI - Mother-infant feeding interaction in full-term small-for-gestational-age infants. AB - Maternal and infant behavior during feeding was assessed in 30 mother-infant dyads: 15 small-for-gestational-age (SGA) infants (birth weights below the 10th percentile) and 15 appropriate-for-gestational-age (AGA) infants (birth weights between the 25th and 90th percentiles). The groups were balanced for gestational age, sex, neonatal risk factors, and maternal age, parity, socioeconomic status, and race. Behaviors indicative of infant feeding difficulties were coded for mother and infant. The SGA mothers had higher frequencies of these behaviors than did their AGA counterparts. Qualitative ratings of interactive behavior were recorded for mother and infant: SGA infants had ratings indicative of less optimal interactions than those of the AGA group. Infant caloric intake (calories per kilogram per feeding) was calculated by first dividing the change in infant weight in grams before feeding and immediately after feeding by the infant's weight before feeding and then converting it to calories. Although no difference in caloric intake was observed between the two groups, infant behaviors and ratings were associated with caloric intake. These data suggest the importance of including neonatal behavior during feeding in the risk assessment of potential growth failure in SGA infants. PMID- 3335957 TI - Cyclosporine for juvenile dermatomyositis. PMID- 3335956 TI - Significance of delta-aminolevulinic acid dehydratase in lead poisoning. PMID- 3335958 TI - Kyphosis in achondroplasia: probably preventable. PMID- 3335959 TI - Genital Mycoplasma infections in neonates. PMID- 3335960 TI - Natural killer cell activity in celiac disease in children on a gluten-free diet and after gluten challenge. PMID- 3335961 TI - Alpha-chain disease in children. PMID- 3335962 TI - Pancreatic exocrine insufficiency in a patient with nephropathic cystinosis. PMID- 3335963 TI - A case of glutaric acidemia type I: effect of riboflavin and carnitine. PMID- 3335964 TI - Pulmonary hypertension in infants with bronchopulmonary dysplasia. AB - Seventeen children with oxygen-dependent bronchopulmonary dysplasia, right ventricular hypertrophy, and Doppler echocardiographic evidence of pulmonary hypertension were studied by cardiac catheterization. Fifteen of these patients had pulmonary hypertension when placed in room air; six of these 15 patients were shown to have large systemic-to-pulmonary collateral vessels. The hemodynamic responses to oxygen and hydralazine were evaluated. Five patients developed normal pulmonary artery pressure while receiving supplemental oxygen and were not studied further. Of the remaining ten patients, the six patients with large, hemodynamically significant collateral vessels all had deleterious reactions to hydralazine. Two of the four patients without collateral pulmonary circulation responded to hydralazine with further reductions in mean pulmonary artery pressure. Five of the ten patients who had persistent pulmonary hypertension while receiving oxygen have died. Cardiac catheterization and angiography may provide important diagnostic, therapeutic, and prognostic information in patients with pulmonary hypertension complicating bronchopulmonary dysplasia. PMID- 3335965 TI - Lack of evidence for craniofacial dysmorphism in perinatal human immunodeficiency virus infection. AB - Thirty children perinatally exposed to human immunodeficiency virus (HIV) infection and 30 healthy control subjects matched for age, sex, and race were evaluated for growth, head size, craniofacial dysmorphism, dermatoglyphics, and other physical features. Thirteen patients met the criteria for group IV (constitutional, neurologic, and secondary infectious diseases), 14 for group III (persistent generalized lymphadenopathy or hepatosplenomegaly), and three for group II (asymptomatic infection) of the classification of HIV infection established by the Centers for Disease Control, Atlanta. Postnatal growth failure and microcephaly, observed in a significant proportion of patients (46.7% and 30%, respectively), could be attributed to chronic illnesses and to progressive central nervous system lesions in HIV-infected patients. There were however, no significant differences between patients and controls with regard to the incidence of craniofacial features and dermatoglyphics, and the incidence of other anomalies was not different from that expected in the population. The patients born to drug-using mothers were not different from those born to non drug-using mothers in relation to the studied criteria. We could not confirm the presence of characteristic craniofacial dysmorphism in children exposed to perinatal HIV infection. PMID- 3335966 TI - Growth failure in bronchopulmonary dysplasia: elevated metabolic rates and pulmonary mechanics. AB - Growth failure is a major problem in infants with bronchopulmonary dysplasia (BPD), but the cause is unknown. We studied 13 infants with BPD but without other medical problems that could contribute to growth failure at 6 months' corrected age. We measured resting oxygen consumption (Vo2), Pao2, airway resistance, specific airway conductance, and dynamic pulmonary compliance (Cdyn) by body plethysmography and growth. Growth failure was defined as height and weight less than the tenth percentile of the Babson growth curves. Vo2 in infants with growth failure and BPD was markedly elevated compared with that in control infants and infants with BPD and normal growth. Vo2 showed an inverse correlation with body weight in infants with BPD but not in control infants. Although Vo2 was inversely related to Cdyn, the total work of breathing only partially explained the increased metabolic demands of the growth failure group. We speculate that growth failure in infants with BPD is partially the result of increased metabolic demands from increased work of breathing but that other mechanisms may act to elevate the metabolic expenditure of these infants. PMID- 3335968 TI - The impact of intrauterine and postnatal malnutrition on the development of the exocrine pancreas and small intestine. PMID- 3335967 TI - Effect of head position on distribution of nasal airflow in preterm infants. AB - Supine preterm infants characteristically adopt a lateral head position; however, it is not known whether this influences the distribution of nasal airflow. Ventilation was measured in 12 healthy preterm infants (postconceptional age 34 +/- 2 weeks) by employing a nasal mask pneumotachygraph that separated airflow between the left and right nasal passages. In the midline supine position, the percent of total tidal volume (%VT) through the right nasal passage ranged from 31% to 64% and varied by less than 5% between active and quiet sleep in any infant. Lateral positioning of the head caused %VT to increase on the dependent side and decrease through the upper nasal passage. When the right side was dependent, mean %VT on that side increased from 52 +/- 9% to 67 +/- 14% (P less than 0.01) and decreased to 43 +/- 10% (P less than 0.05) when the right side was up. In the midline position, the presence of a nasogastric tube caused %VT through the nasal passage with the tube to fall from 54 +/- 8% to 39 +/- 8% (P less than 0.01). The %VT fell farther, to 25 +/- 10% (P less than 0.01), when the nasal passage with the nasogastric tube was up. Despite these changes in VT distribution, total VT remained constant during these maneuvers. We speculate that when supine preterm infants adopt a lateral head position, the decrease in airflow through the upper nasal passage results from partial obstruction of the oropharyngeal or nasopharyngeal airway on that side. PMID- 3335969 TI - Variation in zinc, calcium, and magnesium concentrations of human milk within a 24-hour period from 1 to 6 months of lactation. AB - Longitudinal changes in nutrient levels of human milk have been observed with the progression of lactation, but less is known about changes at different feedings during a 24-h period. In this study, calcium, magnesium, and zinc levels were examined in milk obtained from 49 women at every breast feeding during one 24-h period each month for the first 6 months of lactation. Magnesium and zinc concentrations showed significant diurnal variation at each stage of lactation examined, whereas calcium levels were relatively constant. Maximum variations of 7.5, 17, and 48% were observed within a 24-h period in mean levels of calcium, magnesium, and zinc, respectively. Irrespective of variability, zinc and magnesium concentrations in a single milk sample obtained between 10:00 a.m. and 2:00 p.m. were highly correlated with the mean value of samples collected at each feeding during a 24-h period. PMID- 3335970 TI - Effects of cytochalasin B on the synthesis and secretion of plasma proteins by developing rat liver. AB - Antimicrotubular drugs such as colchicine impair plasma protein secretion markedly less from developing liver than from mature tissue, suggesting the reduced participation of microtubules in hepatic protein secretion during liver development. In order to evaluate the possible contribution of microfilaments to protein export by immature liver, we incubated slices prepared from adult and gestation day 19 fetal rat liver for up to 4 h with the antimicrofilamentous agent cytochalasin B and with colchicine in various concentrations. In adult tissue, cytochalasin B did not reduce either the synthesis or secretion of [14C]leucine-labeled proteins and albumin. Cytochalasin B decreased apparent albumin synthesis by fetal liver, but otherwise, its effects on [14C]leucine incorporation did not differ from those observed in the adult. In contrast with leucine, the uptake of [3H]glucosamine into both adult and fetal liver was reduced by cytochalasin B. When this reduced uptake was normalized to that in corresponding control incubations, [3H]glucosamine incorporation into glycoproteins was markedly diminished in fetal slices, but was unaffected in the adult. Despite this age-dependent difference, cytochalasin B only minimally affected glycoprotein secretion in each group. Cytochalasin B never modified the antisecretory effects of colchicine. These results suggest that during early development, liver protein synthesis is more sensitive to toxic effects of cytochalasin B than during adulthood. However, microfilaments are not required for plasma protein export at either time. PMID- 3335971 TI - Food proteins and maturation of small intestinal microvillus membranes (MVM). I. Binding characteristics of cow's milk proteins and concanavalin A to MVM from newborn and adult rats. AB - To study maturational changes of food protein and lectin binding to rat small intestinal microvillus membranes (MVM), MVM were prepared from newborn and adult animals by a modified CaCl2 precipitation technique. Radiolabeled cow's milk proteins [alpha-lactalbumin, alpha-casein, beta-lactoglobulin, bovine serum albumin (BSA)] and the lectin concanavalin A (Con A) were used for incubations. Binding assays were done using miniature ultracentrifugation for separation of unbound material. Binding of Con A to MVM from newborn and adult rats was strong, specific, and saturable. Binding of Con A was inhibited by cold Con A and by the sugar ligand polymer mannan. Adult MVM bound more Con A than newborn preparations. Unlike Con A, binding of cow's milk proteins by MVM was weak, nonspecific, and noninhibitable. Newborn MVM bound more cow's milk proteins than adult controls. This was true for all the proteins tested (p less than 0.001). Binding rose with decreased molecular weight of cow's milk proteins, but molecular weight was not the only determining factor for binding. Trypsin treatment of MVM caused a marked increase of BSA binding in adult but not in newborn preparations. This finding indicated the importance of protein components of MVM for cow's milk protein binding. Maturational changes in protein-lipid interactions and membrane fluidity possibly influence nonspecific cow's milk protein binding to MVM. Differences in binding between newborns and adults were not directly related to maturational shifts in membrane glycosylation that are indicated by differential Con A binding. Increased cow's milk protein binding in newborn individuals might increase the potential risk to develop an adverse reaction to food proteins. PMID- 3335973 TI - Biliary atresia and meconium ileus associated with Niemann-Pick disease. AB - A boy, and 10 months later his sister, presented in the neonatal period with meconium ileus. Both became jaundiced and were found to have biliary atresia and Niemann-Pick disease, type C. The causes of the meconium ileus were not established. Both died before the age of 6 weeks. PMID- 3335972 TI - Food proteins and maturation of small intestinal microvillus membranes (MVM). II. Binding of gliadin hydrolysate fractions and of the gliadin peptide B3142. AB - To investigate in vitro interactions between gliadin peptide fractions that have been shown to be toxic to celiac small intestinal mucosa in humans and small intestinal microvillus membranes (MVM) from rats during postnatal maturation, MVM were prepared from newborn, 18-day-old preweanling, and adult rats. Partially hydrolyzed gliadin peptide fractions B1-B4, and the pure gliadin peptide B3142 were radioiodinated and used for binding assays. Miniature ultracentrifugation was used for separation of unbound material. Binding of gliadin fractions to MVM was weak and nonspecific in terms of lacking saturation and inhibition. There was no inhibition of binding by mannan. Enzyme pretreatment of MVM (trypsin, neuraminidase, phospholipase C) did not result in any significant change of binding. Compared with peptides prepared from bovine serum albumin as a control, there was no significant difference in binding of gliadin peptide fractions to MVM. Thus, a lectin-like effect of gliadin peptides toward MVM, or the existence of a specific intestinal surface receptor for gliadin peptides appeared improbable. There were, however, consistent maturational changes in MVM binding in that newborn MVM bound more B1-B4 and B3142 compared with adult controls (p less than 0.001). Nonspecific binding of gliadin fractions to MVM might be related to the initiation of nonspecific in vitro effects of gliadin, particularly toward the immature small intestine. The MVM binding model in the rat clearly does not provide a system for studying celiac disease pathogenesis, but it might help clarify basic processes in the interaction between food-derived substances and elements of the gastrointestinal mucosal barrier. PMID- 3335974 TI - Spontaneous perforation of common bile duct. AB - A 2-week-old Micronesian infant presented with spontaneous perforation of the common bile duct. Mild jaundice, acholic stools, and heavily bile-stained ascites were the main clinical features. The presentation of this rare disorder is characteristic enough to permit early diagnosis. Surgery is the treatment of choice. PMID- 3335975 TI - Giant inflammatory polyposis causing partial obstruction and pain in "healed" ulcerative colitis in an adolescent. AB - A 16-year-old boy with chronic ulcerative colitis developed unexplained increasingly intractable abdominal pain and rectal bleeding over several months during a period when acute colitic attacks were quiescent. No abdominal mass was palpable. The cause of symptoms was subtotal colonic obstruction due to the development of massive or giant inflammatory (pseudo) polyposis, which had caused nearly complete obliteration of the lumen of the transverse colon. The radiological and histopathological findings are presented; this case confirms the conclusion drawn in a recent retrospective surgical pathology report that giant inflammatory polyposis may produce distinct symptoms, especially pain, independent of the existence of relatively quiescent underlying inflammatory bowel disease. This unusual complication of inflammatory bowel disease deserves greater clinical awareness. PMID- 3335976 TI - Anaphylactic shock due to cow's milk protein hypersensitivity in a breast-fed infant. AB - A newborn infant developed anaphylactic shock three times, once after ingesting his mother's milk and once after ingesting a formula containing casein hydrolysate. Symptoms resolved after cow's milk was withdrawn from the mother's diet and lactation was resumed. The case demonstrates that anaphylactic shock may occur in breast-fed infants and emphasizes the need to consider allergic phenomena even in these infants. PMID- 3335977 TI - Expression of MHC class II determinants by jejunal epithelium in coeliac disease. PMID- 3335978 TI - The use of nifedipine for treatment of achalasia in children. PMID- 3335979 TI - Ileoscopy and its clinical role in the assessment of backwash ileitis in children with ulcerative pancolitis: Belgrade experience. PMID- 3335980 TI - Does earlier admission in infantile hypertrophic pyloric stenosis (IHPS) apparently increase incidence rates? PMID- 3335981 TI - Comparison of bilirubin production in Japanese and Caucasian infants. AB - Bilirubin production, as indexed by serum carboxyhemoglobin (HbCOc), was studied in a group of normal term Japanese infants and Caucasian controls during the second to third day of life. Stringent entry criteria were employed in order to eliminate infants with hemolysis or other known causes of increased bilirubin production. The mean HbCOc of the Japanese infants (0.69 +/- 0.15% sat) was significantly higher than that of the Caucasian infant (0.58 +/- 0.17% sat). The serum total bilirubin was also significantly higher in Japanese infants (11.1 +/- 3.0 mg/dl versus 8.0 +/- 2.2 mg/dl). This difference may be attributable to environmental and/or genetic factors. PMID- 3335982 TI - Are steroids contraindicated in HBsAg-positive individuals with liver disease? PMID- 3335983 TI - Age and diet effects on fecal bile acids in infants. AB - Fecal bile acid patterns and concentrations have been determined for 28 infants who were followed from average ages of 3-11 months. Half were solely breast-fed and half were solely formula-fed at the beginning of the study. Breast-fed infants were found to have significantly (p less than 0.05) lower concentrations of cholic acid than the formula-fed group, up to an average age of 5 months. Concentrations of deoxycholic and lithocholic acids were directionally lower in breast-fed infants at all ages. Concentrations of chenodeoxycholic acid were similar for both groups throughout the study. At the end of the study, breast-fed infants were excreting 17% of their total bile acids in the form of secondary acids, compared to 33% for formula-fed infants. This pattern persisted long after the infants began weaning. Formula-fed infants were found to have lithocholic acid in their stools at a significantly (p less than 0.05) earlier age than breast-fed infants. Appearance of deoxycholic acid was at similar ages for both groups. Both of these secondary acids were found to occur at much younger ages (approximately 2 months) than has been previously reported. These observed differences are attributed to the distinct intestinal microbial populations encouraged by the different diets. PMID- 3335984 TI - Familial neonatal hemochromatosis with survival. AB - We report two sisters with neonatal hemochromatosis (NHC), including the first documented survivor. Characterized by excessive parenchymal iron in liver, pancreas, heart, and other organs, but little iron in the spleen, bone marrow, or other sites of the reticuloendothelial system, NHC is rarely reported and has been uniformly fatal. The first infant (case 1) presented with neonatal hypoglycemia, coagulopathy, and mild hyperbilirubinemia; she rapidly deteriorated and died of multisystem failure. Autopsy showed cirrhosis. Her sister (case 2) presented similarly; liver biopsy showed giant cell hepatitis, which is consistent with idiopathic neonatal hepatitis (INHP). However, iron staining revealed that case 1 had extensive iron deposits in the liver, pancreas, heart, thymus, and bone, but none in bone marrow or spleen. Case 2 had grade 4 liver iron staining, normal bone marrow iron, elevated serum ferritin and transferrin saturation, and HLA-A3 haplotype. At 16 months of age, the growth, development, and serum measures of iron status in case 2 were normal; liver biopsy showed fibrosis, negative iron staining, and normal tissue iron concentration. NHC is compatible with survival, has clinicopathologic features that overlap with INHP, and may frequently be misdiagnosed as INHP. A prospective study is needed to determine the incidence and natural history of NHC--a disorder that may be more common than is currently recognized. PMID- 3335986 TI - Clinical and laboratory correlates of esophagitis in young children. AB - To develop clinical and laboratory criteria to identify young children with gastroesophageal reflux (GER) who are at particular risk for esophagitis and then to monitor their clinical course we have prospectively studied 40 subjects (ages 2-22 months, mean 8 months) with persistent symptoms of GER with 18 h intraesophageal pH monitoring, endoscopy, and grasp and suction esophageal biopsies. Esophagitis was found in 16 of 20 patients under 7 months, 12 of 14 between 7 and 12 months, and five of six between 12 and 24 months. Esophagitis was equally frequent in those patients with or without poor weight gain, wheezing, or irritability. Only 15% of patients with esophagitis had occult blood in their stool. No parameter of intraesophageal pH monitoring was both sensitive and specific in identifying patients who were ultimately found to have either mild or severe esophagitis. Follow-up data (37 patients) revealed that fundoplication was eventually required in four of eight patients with severe esophagitis, three of 22 with mild esophagitis, and none of seven without esophagitis. Currently used clinical and laboratory assessments of GER have limited value in identifying those children with either normal esophageal mucosa or at risk for varying degrees of esophagitis. Preliminary observations suggest that the presence of severe histologic esophagitis at the time of initial evaluation may have prognostic value in identifying those patients most likely to fail medical therapy and require fundoplication. PMID- 3335985 TI - Simultaneous pH recordings from multiple esophageal sites in children with and without distal gastroesophageal reflux. AB - We made continuous, simultaneous recordings of esophageal pH from three sites in the esophageal body, for 18-24 h, in 11 children with normal prolonged distal esophageal pH studies (Group I) and in 14 children with abnormal distal esophageal pH recordings (Group II). A flexible catheter housing four antimony microelectrodes was used, and data were stored in a portable recorder. A computer allowed for evaluation of the percent of time esophageal pH was less than 4.0, number of reflux episodes per hour, acid clearance time, and the duration of longest reflux episode. Recordings made while subjects were upright or recumbent could be distinguished and analyzed separately. In the recumbent position, comparison of pH recordings from distal, middle, and proximal esophageal pH electrodes in Group I showed significant decreases in the percent of time spent with pH less than 4.0, reflux episodes per hour, acid clearance time, and duration of longest reflux episode in the proximal esophageal sites, with a near negligible total acid exposure in the most proximal electrode. In Group II subjects, however, comparison of recumbent recordings from distal, middle, and proximal esophagus indicates that the proximal esophagus is highly exposed to acid reflux and that the decrease in acid exposure from distal to proximal esophagus in reflux patients is not proportionally as great as that of Group I. The data suggest that in the recumbent position, the ability of the subjects with abnormal reflux scores to protect the upper esophagus is less than that of subjects with normal amounts of distal esophageal acid exposure. PMID- 3335987 TI - Fecal bile acids as a means of assessing the integrity of the enterohepatic circulation of bile acids and their microbial degradation. PMID- 3335988 TI - A randomized study of oral metoclopramide in small bowel biopsy of infants and children. AB - As an intravenous injection is not used in our premedication of infants and children for small bowel biopsy, we investigated what effects oral metoclopramide might have on small bowel biopsy procedure time and fluoroscopy time. Eighteen infants and children were randomized to receive 0.2 mg/kg metoclopramide or placebo orally, 40-45 min before starting the procedure, and the procedure was monitored for the time required for the biopsy capsule to reach the pylorus, to cross into the proximal duodenum, and to reach the biopsy site. Corresponding fluoroscopy times were recorded as well. Mean total procedure time was less for those treated with metoclopramide, 43.7 +/- 11 min, than for controls, 86.5 +/- 15.5 min (p less than 0.005). Mean total fluoroscopy time was also less in treated patients (40.9 +/- 11.5 s versus control 84.4 +/- 17 s) (p less than 0.005). The effect of metoclopramide occurred in the interval for the biopsy capsule to cross the pylorus (15.1 +/- 2.7 min versus control 60.8 +/- 16.6 min) (p less than 0.005) and in fluoroscopy time required (15.1 +/- 1.9 s versus control 46 +/- 17 s) (p less than 0.005). Oral metoclopramide is effective in reducing procedure time for small bowel biopsy, and its predictable action facilitates reduction in fluoroscopy exposure. PMID- 3335989 TI - Effect of soy protein on the small bowel mucosa of young infants recovering from acute gastroenteritis. AB - The effect of soy protein on the small bowel mucosa of 18 infants with acute gastroenteritis was studied. The infants were maintained on a protein hydrolysate formula for 6-8 weeks, following which they were readmitted for soy protein challenge studies. Jejunal biopsy was performed before and 24 h after challenge. On the basis of the clinical and histological reaction to soy protein challenge, three groups were identified. Group 1 consisted of three infants who had clinical and histological reaction. There was associated depletion of mucosal enzymes, lactase, sucrase, malatase, alkaline phosphatase, and blood xylose levels. Group 2 consisted of seven infants who had histological reaction but no clinical symptoms. Two of these seven infants, however, developed clinical reaction when rechallenged with soy protein 2 and 90 days later. Following challenge, mucosal enzymes and blood xylose levels were depressed in five of the seven infants tested. Group 3 consisted of eight infants who did not have either a clinical or a histological reaction. The mucosal enzymes and blood xylose levels were not depressed in four infants tested. The present study shows that the small bowel mucosa of some young infants recovering from acute gastroenteritis remains sensitive to soy protein for a variable period of time. The feeding of soy protein to these infants may result in the persistence of mucosal damage and perpetuation of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3335990 TI - Comparison of two special infant formulas designed for the treatment of protracted diarrhea. AB - The nutritional management of intractable diarrhea and short bowel syndrome remains a challenging problem. The advantage of continuous nasogastric infusion is undisputed, but what to feed remains in question, and no studies, to these authors' knowledge, have yet compared two widely used specially designed protein hydrolysate formulas. A randomized crossover trial of two periods of 7 days was carried out with Alfare and Pregestimil administered by a constant infusion pump in six malnourished infants aged 1-13 months. Two had intractable diarrhea, and four the short bowel syndrome. Identical quantities of calories were administered during the two periods. There was good tolerance for both formulas and satisfactory weight gain. Despite compositional differences related to osmolality, the source of the hydrolysates and their profile, and the qualitative pattern of the carbohydrates, no difference was observed with regard to stool weight, Na+ and K+ losses, and the enteral absorption of fat, carbohydrate derived energy, and total energy. The percent absorption of nitrogen was somewhat higher (p less than 0.01) with Pregestimil (83.8 +/- 2.7) than with Alfare (77.3 +/- 3.4), but nitrogen retention was unaffected. Energy absorption was the same on both formulas, but maldigested or malabsorbed carbohydrates accounted for 63% of total energy loss during Alfare feeding and 72% during the week of Pregestimil. These data call for studies with protein hydrolysate formulas reformulated with a lower concentration of carbohydrates and a higher one of fat. PMID- 3335991 TI - Comparison of nitrogen utilization of two elemental diets in patients with Crohn's disease. AB - Energy, nitrogen absorption, and nitrogen utilization of two commercial elemental diets, Vivonex and Vital, were compared in 10 teenage boys and girls with Crohn's disease. The diets were given in random order as overnight feedings and were the sole source of nutrients for two consecutive periods of 3 weeks each. Urine and stools were collected for 48 h at the end of each 3-week period. Energy absorption was slightly better on Vivonex (p less than 0.05), although 95-100% of energy was absorbed with both formulas. Nitrogen absorption was not different for the two formulas, but nitrogen utilization was significantly better on Vital (28.6 +/- 12.9% versus 9.7 +/- 17.7%, p less than 0.01). This difference may be attributable to the different concentrations of sulfur-containing and aromatic amino acids in the two formulas. PMID- 3335992 TI - Motilin levels in term neonates who have passed meconium prior to birth. AB - Motilin levels were measured by radioimmunoassay from umbilical cord blood obtained at birth from 38 term neonates (median gestational age 40 weeks, range 39-42 weeks). Birth weights of these neonates ranged from 2,840 to 4,593 G (median 3,600 G). Forty-two percent (16/38) of these neonates passed antenatal meconium. The median motilin level was 177 fmol/ml in those neonates who passed antenatal meconium and 111.5 fmol/ml in those neonates who did not pass meconium prior to birth (p less than 0.01). Although fetal distress has been found to be associated with elevated motilin levels at birth, such an association was not found in this study. These data support an association between elevated motilin levels at birth and antenatal meconium passage. PMID- 3335993 TI - Preclinical pharmacology of a new serotonergic receptor antagonist, LY281067. AB - The preclinical pharmacologic activity of LY281067 shows it to be a potent and highly selective serotonergic (5-HT2) receptor antagonist. Based upon binding studies with 5-HT2 receptors in brain cortical membranes and block of 5-HT induced contractions in the rat jugular vein, LY281067 showed high affinity at 5 HT2 receptors with a dissociation constant of approximately 1 nM. Furthermore, LY281067 was a highly selective 5-HT2 receptor antagonist without appreciably binding to 5-HT1, D1 or D2 receptors or interacting with histamine (H1), cholinergic, beta adrenergic or alpha-1 adrenergic receptors in smooth muscle. LY281067 had modest affinity at alpha-2 receptors with a dissociation constant of approximately 100 nM. Oral bioavailability of LY281067 in spontaneously hypertensive rats was excellent with an oral to i.v. dose ratio approximating 4, based upon blockade of pressor responses to 5-HT as an in vivo estimate of 5-HT2 receptor antagonist activity. Furthermore, LY281067 blocked quipazine-induced increase in serum corticosterone concentration, an increase thought to be mediated by activation of central 5-HT receptors. After oral administration to rats, LY281067 antagonized vascular 5-HT2 receptors with a relatively long duration of action (greater than 6 hr), an observation likely to be related to plasma concentrations of both the parent and an active metabolite. Lastly, LY281067 was relatively nontoxic, possessing a therapeutic index of approximately 1000 after oral administration to rats. In summary, LY281067 is a potent and highly selective, orally active 5-HT2 receptor antagonist with a relatively long duration and wide margin of therapeutic safety. PMID- 3335994 TI - Role of dapsone hydroxylamine in dapsone-induced hemolytic anemia. AB - The hemolytic anemia which frequently accompanies treatment of individuals with dapsone and other arylamine drugs is believed to be caused not by the parent drugs per se, but rather by metabolites which are formed during the clearance of the drugs in vivo. To determine whether the N-hydroxyarylamine metabolites of dapsone could be responsible for dapsone-induced hemolysis, dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine were administered to rats which had previously received 51Cr-labeled red blood cells. All three compounds caused an increase in the rate of disappearance of radioactivity from the blood as compared with saline-treated controls. In parallel in vitro studies, incubation of 51Cr-labeled red blood cells with DDS-NOH, but not dapsone or monoacetyldapsone, induced a decrease in survival time of the radiolabeled cells when they were reintroduced into isologous rats. The disappearance of radioactivity from the blood was matched by its selective uptake into the spleen. The amount of damage (as measured by decreased red cell survival in vivo) was proportional to both concentration and time of exposure to DDS-NOH. The area under the blood concentration vs. time curve for total arylhydroxylamines (DDS NOH + monacetyldapsone hydroxylamine) in rats given a hemotoxic dose of dapsone was similar to that of rats given an equitoxic dose of DDS-NOH. Collectively, these data indicate that the hydroxylamine metabolites of dapsone are direct acting hemolytic agents that are formed from dapsone in sufficient amounts to account for their being the sole mediators of dapsone-induced hemolytic anemia in the rat. PMID- 3335995 TI - Acute physical dependence in man: effects of naloxone after brief morphine exposure. AB - This study assessed the effects of i.m. naloxone (10 mg) 6 hr after acute i.m. injections of morphine (0, 1, 3, 5.6, 10 and 17 mg). Naloxone reversed residual morphine-produced respiratory depression, miosis and subjective reports of drug "high." In addition, naloxone precipitated signs and symptoms characteristic of opioid withdrawal. Subjective report measures of "bad" drug effects and specific opioid withdrawal symptoms increased as a function of morphine pretreatment dose, as did observer-rated signs of withdrawal. Yawning was the most prominent observed sign, whereas yawning and irritability were the most consistently reported subjective symptoms. Peak withdrawal effects were seen within 15 min post-naloxone. The results of this study confirm previous reports of acute physical dependence in man and extend those findings by demonstrating a morphine dose-response function. PMID- 3335996 TI - Application of [125I]iodocyanopindolol to measure 5-hydroxytryptamine1B receptors in the brain of the rat. AB - In this study, [125I]iodocyanopindolol ([125I]ICYP), in the presence of isoproterenol, was used to label 5-hydroxytryptamine1B (5-HT1B) receptors in homogenates of the cortex, substantia nigra and caudate-putamen of the rat. The determination of the appropriate concentrations of isoproterenol required to block optimally beta adrenoceptors whereas producing minimal occupancy of 5-HT1B receptors was achieved by generating isotherms for isoproterenol at multiple concentrations of [125I]ICYP. When different concentrations of isoproterenol were used with increasing concentrations of [125I]ICYP, a linear Scatchard transformation of the saturation curve was achieved, even with ligand concentrations about 6-fold greater than the KD for [125I]ICYP. Competition for [125I]ICYP (100 pM) labeled binding sites by 15 serotonin agonists or antagonists was adequately described by a single site model, and the affinity of these drugs for the site labeled by [125I]ICYP was similar to that determined previously when using indirect methods to label 5-HT1B receptors. Serotonin itself showed high affinity for this binding site as did two antagonists, metergoline and methiothepin. By contrast, drugs thought to be selective for the 5-HT1A receptor (e.g., 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone and spiperone) showed very weak affinity for the binding site labeled with [125I]ICYP. The effect of nucleotide regulation on [125I]ICYP binding at 5-HT1B receptors also was evaluated. It was determined that GTP had little effect on the binding of [125I]ICYP, reducing total binding by only 15% and shifting the displacement curve of 5-HT by a factor of less than two. The regulation of 5-HT1B receptors, labeled by [125I]ICYP, also was evaluated. Intraventricular injections of 5.7 dihydroxytryptamine increased significantly the number of 5-HT1B receptors in the caudate-putamen; this treatment had no effect on 5-HT1B binding sites either in the cortex or substantia nigra. The regulatable binding site for [125I]ICYP in the caudate-putamen had a pharmacological profile very similar to that of the 5 HT1B binding site in the cortex. [125I]ICYP appears to be a useful ligand to measure 5-HT1B receptors in the brain of the rat. The localized increase in 5 HT1B receptors in the caudate-putamen after destruction of central serotonergic neurons might indicate that the majority of 5-HT1B receptors in this area of brain are not located on serotonergic nerve terminals. PMID- 3335997 TI - Evidence for the delivery of narcotic antagonists to the colon as their glucuronide conjugates. AB - Morphine-dependent rats were used to evaluate the effects of the narcotic antagonists, naloxone and nalmefene, and their glucuronide conjugates on the gastrointestinal tract and various parameters of brain-mediated withdrawal. When administered s.c. nalmefene HCl caused a dose-dependent tail skin temperature increase, whereas nalmefene glucuronide was ineffective. Nalmefene precipitated brain-mediated morphine withdrawal at doses as low as 10 micrograms/kg, whereas nalmefene glucuronide was ineffective at doses as high as 1 mg/kg. After p.o. administration of the drugs, naloxone HCl and nalmefene HCl caused diarrhea, withdrawal behavior and tail skin temperature responses by 15 min. In contrast, after p.o. administration of the glucuronide conjugate of either narcotic antagonist, diarrhea was delayed for 75 to 203 min. This latency probably reflects the required transit time to the lower gastrointestinal tract inasmuch as direct colonic administration of either nalmefene or nalmefene glucuronide caused diarrhea within 5 to 8 min. Additionally, the magnitude of brain-mediated withdrawal was smaller and its time of occurrence was delayed and compared to the diarrhea response after p.o. administration of the conjugated forms of the narcotic antagonists. Our calculations indicate that about 0.2 to 0.5% of the dose of the narcotic antagonist administered orally as the glucuronide was absorbed systemically. These results indicate that p.o. administration of the glucuronide conjugates of naloxone and nalmefene results in delivery of the narcotic antagonists to the colon. As such these conjugates may be useful in the prevention or relief of constipation caused by opiate use, without interfering with the central analgesic effects of the narcotics. PMID- 3335998 TI - Effects of selected muscarinic cholinergic antagonists on [3H]acetylcholine release from rat hippocampal slices. AB - A number of cholinergic muscarinic (M) agonists and antagonists were studied for their ability to enhance tritiated acetylcholine ([3H]ACh) release from electrically field-stimulated rat hippocampal slices. A Ca++-free medium and carbachol, but not nicotine, inhibited [3H]ACh release. Atropine, methylatropine and dexetimide produced concentration-dependent increases in [3H]ACh release to a maximum of about 50% above control. Aprophen and benactyzine produced a maximal response 25 to 35% above control. The selective M1 antagonist pirenzepine had the least effect on [3H]ACh release. Of the nonspecific M1-M2 antagonists studied, benactyzine produced the least amount of [3H]ACh release. The order of potency of the M antagonists in promoting a 15% increase in [3H]ACh release was aprophen greater than benactyzine greater than methylatropine greater than dexetimide greater than pirenzepine greater than atropine. However, the order of promoting maximal release of [3H]ACh was atropine greater than dexetimide greater than methylatropine greater than aprophen greater than benactyzine greater than pirenzepine. PMID- 3335999 TI - Desensitization of adenosine and dopamine receptors in rat brain after treatment with adenosine analogs. AB - Maximally tolerated doses of N6-[(R)-1-methyl-2-phenylethyl] adenosine (0.50 nmol/hr/2 wk), 5'-N-ethylcarboxamide adenosine (NECA, 0.04 nmol/hr/2 wk) or deoxycoformycin (5 nmol/hr/1 wk) were administered i.c.v. to rats using mini osmotic pumps. Adenosine receptor function was subsequently assayed using both ligand binding and adenylate cyclase assays. Binding to A1 receptors was quantitated using [3H]N6-[(R)-1-methyl-2-phenylethyl]adenosine, a selective agonist ligand at A1 receptors. Differences in the binding of this ligand and that of [3H]NECA, which binds to A1 and A2 receptors with similar affinities, were used to quantitate A2 receptors. None of the treatments affected A1 receptor function as assessed by both ligand binding and adenylate cyclase assays. A2 receptor binding and A2 receptor-mediated stimulation of adenylate cyclase were blunted in striatal membranes from NECA- and deoxycoformycin-treated rats but unaffected in striatal membranes from N6-[(R]-1-methyl-2-phenylethyl]adenosine treated rats. All three pretreatments attenuated D1 dopamine receptor-mediated stimulation of adenylate cyclase in striatal membranes. These results suggest that 1) the A2 adenosine receptor system is susceptible to desensitization and 2) different mechanisms are involved in the NECA- and deoxycoformycin-induced desensitization of A2 adenosine receptor and D1 dopamine receptor systems. It is suggested that the D1 dopamine receptor desensitization is, in fact, due to the tonic stimulation of adenosine A1 receptors. PMID- 3336001 TI - Differential antagonism by naltrexone of the effects of opioids on a fixed-ratio discrimination in rats. AB - In the presence of a stimulus above the center lever, rats were required to complete one of two fixed-ratios (FRs) on the center lever (FR 8 or FR 16). Completion of the ratio turned off the center-lever stimulus and produced a stimulus above each of the two side levers. If the completed ratio was high (e.g., FR 16), a response on the left lever produced a food pellet. If the ratio was low (e.g., FR 8) a response on the right lever produced food. Errors produced a brief timeout. When administered alone, morphine, cyclazocine, pentazocine, dl N-allylnormetazocine (NANM), d-NANM, I-NANM and phencyclidine each produced dose related decreases in accuracy and response rate. Ketocyclazocine decreased response rate in a dose-related manner but had little or no effect on accuracy. Naltrexone (0.1 mg/kg) shifted to the right by approximately 0.75 log unit the morphine dose-effect curves. This same dose of naltrexone tended to produce greater antagonism of the effects of pentazocine on accuracy than on rate which was shifted by only 0.25 log unit. Naltrexone (0.1 mg/kg) produced little or no antagonism of the effects of cyclazocine, whereas naltrexone (1 mg/kg) shifted the dose-effect curves to the right by about 0.25 log unit. Naltrexone (0.1 and 1 mg/kg) shifted the ketocyclazocine dose-effect curves to the right by approximately 0.5 and 1 log unit, respectively. Although variable among subjects, across a range of doses (0.1-10 mg/kg), naltrexone failed to antagonize the effects of dl-NANM, d-NANM, l-NANM and phencyclidine. Rather, in some subjects naltrexone tended to shift the dose-effect curves to the left. Fluphenazine (0.1 mg/kg) also failed to antagonize the effects of d-, l-NANM and phencyclidine. In summary, whereas mu and sigma agonists produce qualitatively similar effects on the performance of a discrimination in the rat, they do so through different mechanisms of action. PMID- 3336000 TI - Pharmacodynamic model of tolerance: application to nicotine. AB - The authors propose a model of pharmacodynamic response that, when integrated with a pharmacokinetic model, allows characterization of the development of functional tolerance. The model may be conceived of in several equivalent ways; one of these sees tolerance as a result of (noncompetitive) antagonism of agonist effect by a hypothetical substance (e.g., metabolite) produced by a first-order process, driven by agonist concentration. Tolerance thus lags behind, and is approximately proportional to, agonist concentrations. Two new parameters quantifying tolerance are introduced: kantO, which describes the elimination kinetics of the antagonist and determines the rate of development and disappearance of tolerance, and Cant50, which determines the magnitude of tolerance that can be achieved. The model was tested in eight volunteers on data produced after three sequences of paired i.v. administrations of nicotine separated by different intervals of time. Blood concentrations of nicotine and heart rate were measured. The proposed tolerance model was fitted to the nicotine data. The estimate of kantO suggests a half-life of development and regression of tolerance of 35 min, and the estimate of Cant50 suggests that tolerance, at its full development, causes an approximately 80% reduction of initial (nontolerant) effect. This model provides a quantitative pharmacokinetic-pharmacodynamic description of the development of acute tolerance that also carries physiologic meaning. The quantitative information provided by this model may improve understanding of the temporal patterns of drug abuse and complications thereof. PMID- 3336002 TI - Cross-tolerance and cross-sensitization between morphine analgesia and naloxone sensitive and cimetidine-sensitive stress-induced analgesia. AB - Recent studies have shown that different regimens of footshock elicit either "opiate" (naloxone-sensitive) or "histaminergic" (cimetidine-sensitive but naloxone-insensitive) analgesic responses. Presently, the nature of these responses was further investigated by characterizing the development of tolerance to these stress paradigms and by assessing the degree of cross-tolerance between these treatments and morphine (MOR) in rats. Daily exposure to the "opiate" stress paradigm for 7 days resulted in a significant loss of this form of footshock-induced analgesia (FSIA), but the same exposure to the "histaminergic" regimen resulted in no such tolerance. One day later, animals from the "opiate" stressed group exhibited MOR analgesia that was comparable to that in unstressed animals, whereas animals chronically exposed to the "histaminergic" paradigm showed highly potentiated responses to MOR. However, when naive animals were made tolerant to MOR, acute "opiate" FSIA was significantly attenuated, whereas the "histaminergic" analgesia was unaffected. These results, showing one-way cross tolerance between MOR and "opiate" FSIA, are consistent with the hypothesis that opiate FSIA uses a subset of opiate receptors activated by systemic MOR. The one way cross-sensitization between MOR and "histaminergic" analgesia observed presently, taken with previous findings, suggests that opiate-containing and histamine-containing neurons comprise separate endogenous analgesic systems that mutually inhibit each other. The absence of tolerance and opiate cross-tolerance exhibited by the cimetidine-sensitive analgesia suggests that drugs designed to activate this analgesic system should be devoid of such liabilities. PMID- 3336003 TI - Conjugative clearance of 1-naphthol and disposition of its glucuronide and sulfate conjugates in the isolated perfused rat kidney. AB - Extensive extrahepatic metabolism of 1-naphthol (1-N) was shown to occur in the rat in vivo (clearance = 377 ml/min/kg). The renal contribution to the metabolism of 1-N was investigated in the isolated perfused rat kidney (IPK). 1-N was metabolized to its sulfate (1-NS) and glucuronide (1-NG) conjugate by the IPK. The renal clearance of 1-N ranged from 5.36 to 6.24 ml/min/kidney and was 80 to 95% of the p-aminohippuric acid clearance by the IPK. This indicated that the renal extraction ratio of 1-N was 0.80 to 0.95, showing an important contribution of renal metabolic clearance to the total clearance. Nonlinear kinetics, due to saturation of the metabolic pathways, was shown at 1-N concentrations higher than 10 microM. 1-NS and 1-NG are both secreted in the urine and perfusate, although the urinary excretion of 1-NS is very small whereas the excretion of 1-NG into the urine is extensive, due to differences in the active secretion and protein binding of both conjugates. PMID- 3336004 TI - The endothelium inhibits the penetration of serotonin and norepinephrine in the isolated canine saphenous vein. AB - Serotonin can accumulate in the adrenergic nerves of vascular tissues. We have determined whether in the isolated perfused dog saphenous vein 1) luminal administration of serotonin can result in its accumulation in the adrenergic nerves and 2) endothelium can interfere with the transport of the amine into the vessel wall. Saphenous veins were perfused with medium containing [3H]serotonin, [3H]norepinephrine or [3H]epinephrine; after washout, significant amounts of 3H were detected in the veins. The 3H-accumulation was augmented when the endothelium was removed mechanically; the augmented accumulation was only observed when the [3H]amines reached the tissues from the intimal side. In coronary arteries perfused with [3H]serotonin, similar results were obtained. No increased 3H-accumulation was noted in veins without endothelium perfused in the presence of cocaine. Nerve stimulation of veins labeled with [3H]serotonin caused an augmented release of 3H from the tissues without endothelium. Pargyline augmented the accumulation of [3H]serotonin and [3H]norepinephrine and decreased the difference between tissues with or without endothelium only for norepinephrine. Perfusion of venous segments with platelets, labeled with [3H]serotonin, resulted in a 3H-content which was significantly higher in the veins without endothelium. Our experiments show that serotonin and other amines, applied luminally to perfused blood vessels, can accumulate in the adrenergic nerves and that the endothelium can reduce this accumulation. Serotonin, originating from aggregating platelets, can penetrate the vessel wall much easier at sites of endothelial denudation and this serotonin also can enter the adrenergic nerves. PMID- 3336005 TI - Differential response of normal and cirrhotic liver to vasoactive agents. A study in the isolated perfused rat liver. AB - In cirrhosis, endogenous vasoactive agents could act as modulators of intrahepatic resistance and thus portal pressure. The aim of this work was to study the effects of norepinephrine, angiotensin II and arg8-vasopressin on intrahepatic portal resistance in isolated perfused livers from normal rats and rats with carbon tetrachloride-induced cirrhosis. Livers were perfused at a constant pressure and the measured variable was portal blood flow. Dose-response curves were obtained by cumulative addition of agonists to the perfusate. The three vasoactive agents increased resistance in normal and cirrhotic livers. The maximal amplitude of response was similar in normal and cirrhotic livers. The cirrhotic livers exhibited an increased sensitivity to norepinephrine, a decreased sensitivity to angiotensin II but an unchanged sensitivity to arg8 vasopressin. The shape of the dose-response curve for norepinephrine and arg8 vasopressin, but not for angiotensin II, was modified in cirrhotic livers. We conclude that the cirrhotic liver retains a strong vascular reactivity to vasoactive agents and particularly to norepinephrine. PMID- 3336007 TI - Identification of nonserotonergic [3H]ketanserin binding sites associated with nerve terminals in rat brain and with platelets; relation with release of biogenic amine metabolites induced by ketanserin- and tetrabenazine-like drugs. AB - In mammalian striatal tissue and cat platelets, [3H]ketanserin labels besides serotonin-S2 receptors nonserotonergic saturable binding sites. The sites have been distinguished and characterized in [3H]ketanserin binding assays by selective inhibition with tetrabenazine (Ki = 4 nM), a monoamine depleting agent. In rats, the nonserotonergic ketanserin sites were enriched in the striatum (KD = 12.4 +/- 0.3 nM, maximal number of binding sites = 53.2 +/- 11.8 fmol/mg of tissue at pH 7.7, 37 degrees C) and nucleus accumbens. The sites were decreased by 65 to 78% after 6-hydroxydopamine lesions, suggesting an association with dopaminergic nerve terminals. In in vitro superfusion experiments using [3H]dopamine, [3H]norepinephrine and [3H]serotonin loaded rat brain tissue and [3H]serotonin loaded human platelets, 5 min superfusion with 10(-6) M ketanserin, tetrabenazine and reserpine caused instantaneously a marked increase in tritium efflux. The effect was attenuated by the monoamine oxidase inhibitor, pargyline, in brain slices but not in platelets. High-performance liquid chromatography analysis of endogenous catecholamines, serotonin and metabolites in superfusates from striatal slices revealed that stimulation with these drugs provoked mainly release of 3,4-dihydroxybenzeneacetic acid, homovanillic acid, and 5 hydroxyindoleacetic acid. Potencies of a series of ketanserin derivatives, benzoquinolizine derivatives and a variety of drugs affecting neurotransmission were assessed in the in vitro release test using [3H]dopamine loaded striatal slices, and in [3H]ketanserin binding assays to nonserotonergic sites in the striatum and to serotonin-S2 receptors in brain tissue. Activities of drugs in the release test correlated strongly with their binding affinities for nonserotonergic ketanserin sites (rs = 0.83, n = 30, P less than .001). High potency in the latter two tests was confined to few close structural congeners of ketanserin and tetrabenazine. Distinct structural activity relationships for interaction with nonserotonergic ketanserin sites and serotonin-S2 receptors were found. It was concluded that nonserotonergic ketanserin sites mediate release of oxidated metabolites of biogenic amines from nerve endings and of serotonin from platelets. Hence release of biogenic amine metabolites or of cytoplasmic amines is probably not a mere diffusion process but involves specific membranous molecules. Unlike tetrabenazine, ketanserin caused no obvious depletion of central catecholamine and indoleamine stores. Implications of these findings for the mechanism of action of the drugs are discussed. PMID- 3336006 TI - Effects of cytochalasin-B and phloretin on digitalis inotropy. AB - Phloretin and cytochalasin-B are known to inhibit sugar transport across the cell membrane of many tissues. Both of these agents at concentrations of 100 and 20 microM, respectively, blocked the inotropic effects of ouabain and acetylstrophanthidin (AS) in isolated rabbit atria and papillary muscle preparations. Neither of these agents had any effect of its own on contractile force. Addition of phloretin or cytochalasin-B after the inotropic response to ouabain was fully established did not reverse the effect. The potency of cytochalasin-B was greater in atria than in papillary muscles, 1 microM of cytochalasin caused significant inhibition of the inotropic effect of ouabain in atria without significant effect in papillary muscles. Phloretin but not cytochalasin-B decreased the binding of [3H]ouabain to a semipurified sarcolemmal preparation isolated from canine left ventricular muscle. Neither ouabain nor AS had a substantial positive inotropic effect in atria suspended in substrate-free medium. Substitution of pyruvate (5 mM) for glucose did not fully support their inotropic effect in atria. Papillary muscles behaved differently, in that substrate-free as well as pyruvate media almost fully supported the inotropic effects of ouabain and of low concentrations of AS. Higher concentrations (greater than 250 ng/ml) of As produced a negative inotropic response in substrate-free medium. The possibility that an "active" sugar transport system is required for digitalis inotropy is ruled out by the observation that 2 deoxyglucose also prevents the inotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336008 TI - Evaluation of antagonists of the discriminative stimulus and response rate effects of phencyclidine. AB - The present studies examined whether a variety of drugs representative of diverse pharmacological classes were able to antagonize either the discriminative stimulus or response rate suppressing effects of phencyclidine (PCP). Rats were trained to lever press according to fixed-ratio 32 reinforcement schedules for food pellet delivery and to discriminate PCP from saline vehicle during daily (Monday-Friday) experimental sessions. Drugs combined with PCP to test for antagonism included an alpha-1 (prazosin) and an alpha-2 (yohimbine) adrenergic antagonist, the adenosine receptor agonist, I-phenylisopropyl adenosine, the gamma-aminobutyric acid agonist, imidazole acetic acid, the dopaminergic antagonist, haloperidol, the acylating agent of the PCP receptor, metaphit, and the dopaminergic drugs (+)- and (-)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. All test drugs except metaphit were tested in rats trained to discriminate 2.5 mg/kg of PCP from saline. (+)- and (-)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine were additionally tested in rats trained to discriminate 1.0 mg/kg of PCP from saline. Metaphit was only tested in rats which had been trained to discriminate a 1.0-mg/kg PCP dose. None of the test drugs systematically reduced PCP level selection to vehicle levels. Yohimbine and prazosin, however, but not the other test drugs, partially reversed the response rate reducing effects of PCP. Evidence that alpha adrenergic antagonists have some PCP antagonistic effects were confirmed for the response rate effects of PCP, indicating a possible role of adrenergic mediation of these effects. PMID- 3336009 TI - Electrophysiological effects of amrinone and milrinone in an isolated canine cardiac tissue model of ischemia and reperfusion. AB - The purpose of this study was to determine if amrinone or milrinone after the electrophysiological responses of canine ventricular tissues to "ischemia" or reperfusion. Isolated canine Purkinje tissue-papillary muscle preparations were studied using standard microelectrode techniques. Tissues were superfused for 10 min with a solution that mimicked ischemia (hypoxia, acidosis, elevated lactate levels and zero substrate). Reperfusion with normal Tyrode's solution was then instituted for 60 min. Next, tissues were equilibrated with amrinone (5.3 X 10( 4) M) or milrinone (2.5 X 10(-4) M) for 15 min and the protocol was repeated with drug in all solutions. Without drug, ischemic conditions resulted in moderate depolarization of Purkinje and muscle tissues. Reperfusion caused a rapid hyperpolarization in Purkinje tissue. This was followed by a phase of mild depolarization associated with enhanced pacemaker activity. All preparations recovered by 45 min of reperfusion. With amrinone or milrinone present, the changes in membrane potential induced by conditions of ischemia and reperfusion were not different from control. However, an early phase of very rapid ectopic activity was seen during reperfusion with amrinone or milrinone. This ectopic activity had a constant cycle length during the pauses in stimulation. However, irregular patterns of spontaneous and driven beats were observed when electrical stimulation was superimposed on the ectopic activity. Amrinone and milrinone also increased pacemaker activity in Purkinje tissue but this occurred later in reperfusion. This study demonstrates that amrinone and milrinone sensitize isolated canine ventricular tissues to the arrhythmogenic effects of reperfusion. The mechanism underlying the arrhythmic activity elicited by the bipyridines is not clear, but may involve re-entry or abnormal automaticity. PMID- 3336010 TI - Inhibitory effects of aminoglycosides on renal protein phosphorylation by protein kinase C. AB - Aminoglycosides such as neomycin are commonly prescribed antibiotics; however, there is associated serious damage to the kidney. We examined the effect of aminoglycoside antibiotics on renal protein phosphorylation and found that neomycin selectively inhibited Ca++-activated, phospholipid-dependent phosphorylation of 88-kDa protein in cell lysates of the rabbit kidney. Fifty percent inhibition of phosphorylation of this protein occurred with 5 X 10(-5) to 1 X 10(-4) M neomycin. In living PtK2 cells, neomycin dose-dependently inhibited 12-O-tetradecanoyl-phorbol-13-acetate-induced phosphorylation of 88 K Da protein. This drug also inhibited phosphorylation of exogenous protein catalyzed by protein kinase C, isolated from rabbit kidney in vitro. In contrast, neomycin had little or no inhibitory effect on cyclic GMP-dependent protein kinase, cyclic AMP dependent protein kinase, casein kinase I, casein kinase II and Ca++-calmodulin dependent myosin light chain kinase. Whereas activity of protein kinase C was inhibited 65% by neomycin (0.1 mM) at pH 5 to 7, inhibition decreases to 33% at pH 8 and to zero at pH 9. The potencies of a series of aminoglycoside antibiotics to inhibit the kinase agreed well with number of ionizable amino groups of compounds (gamma = 0.99) and this also approximates their known nephrotoxic potential; amikacin less than or equal to kanamycin less than gentamycin less than or equal to tobramycin less than neomycin. As aminoglycoside antibiotics present in the kidney after administration of toxicological doses (10(-2) M) will inhibit the effects of protein kinase C, the aminoglycoside antibiotics-induced nephrotoxicity is discussed in relation to inhibition of intracellular protein kinase C. PMID- 3336012 TI - Species variation in toxication and detoxication of acetaminophen in vivo: a comparative study of biliary and urinary excretion of acetaminophen metabolites. AB - Acetaminophen (AA) is converted to a toxic electrophile that may subsequently form a glutathione conjugate (AA-GS). In addition to the toxication pathway metabolites, which consist of AA-GS and its hydrolysis products (AA cysteinylglycine, AA-cysteine and AA-mercapturate), detoxication pathway metabolites, such as AA-glucuronide and AA-sulfate, are also formed. In order to evaluate the role of these opposing pathways in the reported species variations in susceptibility to AA-induced liver injury, AA was administered to hamsters and mice, species which are susceptible to AA-induced liver injury, and to rats, rabbits and guinea pigs, species which are relatively resistant to AA-induced liver injury, and the biliary and urinary excretion of AA metabolites were measured simultaneously for 2 hr after administration of AA (1 mmol/kg i.v.). The AA-susceptible species excreted 27 to 42% of the dose as toxication pathway metabolites, whereas the resistant species excreted only 5 to 7% of the dose as toxication pathway metabolites. Most of the toxication pathway metabolites appeared in bile, where their composition reflected hepatic gamma glutamyltranspeptidase activity; hamsters and mice (low gamma glutamyltranspeptidase activity) excreted mainly AA-GS, whereas bile from rabbits and guinea pigs (high gamma-glutamyltranspeptidase activity) contained significant amounts of AA-GS hydrolysis products. Thus, the biliary excretion of AA-GS and its hydrolysis products may be used as an index of toxic activation of AA. The excretion of the detoxication pathway metabolites (AA-glucuronide and AA sulfate) was 74, 62, 41, 27 and 12% of the dose in guinea pigs, rats, mice, rabbits and hamsters respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336011 TI - Ketamine- and morphine-induced analgesia and catalepsy. I. Tolerance, cross tolerance, potentiation, residual morphine levels and naloxone action in the rat. AB - The effects of ketamine and morphine on pain perception and catalepsy were compared in rats. Analgesia, as measured by the latency to withdrawal of the tail from a 55 degrees C water bath (tail-flick latency difference, TFLD), was produced by both ketamine and morphine, but at widely different doses, and in each case the effect was reversed by naloxone. Catalepsy, measured by the duration of loss of righting reflex (DLRR) in catatonic animals, was induced by larger doses of both ketamine and morphine and in each case was reduced by a larger dose of naloxone. DLRR and TFLD tolerance developed rapidly and with a similar time course after daily doses of ketamine or morphine. Rats tolerant to the DLRR effect of ketamine showed cross-tolerance to morphine. Rats tolerant to the DLRR effect of morphine did not show cross-tolerance to ketamine when administered the following day; instead, these rats showed potentiation of the ketamine-induced DLRR. The degree of potentiation noted 24 hr after a single or multiple daily doses of 45 mg/kg of morphine is the same as that seen when 2 mg/kg of morphine is given simultaneously with ketamine. The residual brain level of morphine 24 hr after 45 mg/kg is similar to the level 1 hr after a 2-mg/kg dose. The augmented ketamine response in morphine-tolerant rats is postulated to be a result of residual morphine still present in the brain 24 hr after the last DLRR-inducing dose of morphine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336013 TI - Evaluation of the side arm of (naphthylvinyl)pyridinium inhibitors of choline acetyltransferase. AB - A number of quaternary salts of trans-4-(beta-1-naphthylvinyl)pyridine (NVP) were synthesized and evaluated as inhibitors of the enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Structural variations in the side arm attached to the pyridine nitrogen atom demonstrate that an inductive effect is small but significant for activity. Inhibition of ChAT by alkylated derivatives decreases when electron-withdrawing groups are placed in the side chain. Substitution of a methyl group on the pyridine ring only slightly affects activities toward ChAT and AChE. When the pyridinium moiety is replaced by an imidazolium ring, no ChAT inhibition was observed. The imidazolium compound, however, was a weak inhibitor of AChE. For design of affinity columns for purification of ChAT, the data also supports the use of long chain alkylated amide derivatives of NVP. PMID- 3336014 TI - Tertiary 3- and 4-haloalkylamine analogues of oxotremorine as prodrugs of potent muscarinic agonists. AB - A series of tertiary 3- and 4-haloalkylamines related to the muscarinic agent oxotremorine was synthesized. The compounds cyclized in neutral aqueous solution to quaternary ammonium salts, which, in contrast to the parent haloalkylamines, were potent muscarinic agonists in vitro. When administered systemically to mice, the haloalkylamines produced central (tremor and analgesia) and peripheral (salivation) muscarinic effects. Central potency was dependent on the rate of cyclization and on the route of administration. The N-methyl-N-(4 chlorobutyl)amine derivative 7 cyclized rapidly (t1/2 less than 0.4 min at 37 degrees C) and elicited tremor on iv but not on ip injection, whereas the N methyl-N-(3-chloropropyl)amine 3 cyclized slowly (t1/2 = 436 min) and was not tremorogenic by either route of administration. The N-methyl-N-(3 bromopropyl)amine 4(t1/2 = 11 min) and its iodo analogue 5 (t1/2 = 14 min) were quite potent in eliciting central muscarinic effects on both iv and ip injection to mice. It is concluded that haloalkylamine analogues of oxotremorine may serve in vivo as prodrugs for potent quaternary ammonium salts and that they are capable of circumventing the blood-brain barrier to such salts. PMID- 3336015 TI - Dimethylsulfonium and thiolanium analogues of the muscarinic agent oxotremorine. AB - Dimethylsulfonium (6a and 6b) and thiolanium analogues (7a and 7b) of oxotremorine were synthesized and found to be potent muscarinic agents in vivo and vitro. Compound 6a exceeded oxotremorine in potency. Their affinities for muscarinic receptors in the guinea pig ileum and urinary bladder, estimated pharmacologically, were higher than those of the corresponding trimethylammonium (8a and 8b) and N-methylpyrrolidinium compounds (9a and 9b). However, the new compounds had lower intrinsic efficacies than their quaternary ammonium analogues. The compounds also had high affinity for central muscarinic receptors as measured by displacement of specifically bound (-)-[3H]-N-methylscopolamine from homogenates of the rat cerebral cortex. Half-maximal occupation of cortical muscarinic receptors by 6a, 6b, 7a, and 7b was achieved at concentrations of 0.8, 5.4, 0.3, and 3.3 microM, respectively. The competition curves of 6a, 6b, and 7a were adequately described by a two-site binding equation. The ratio of low- and high-affinity dissociation constants agreed with relative efficacy estimated on the ileum. The thiolanium salt 7a was a fairly potent nicotinic agent on the frog rectus abdominis. PMID- 3336016 TI - Conformational requirements of substrates for activity with phenylethanolamine N methyltransferase. AB - beta-Phenylethanolamines have long been known to be substrates for the enzyme that converts norepinephrine to epinephrine (phenylethanolamine N methyltransferase, PNMT, EC 2.1.1.28). In an effort to determine which, if any, particular conformation of the aminoethyl side chain of phenylethanolamines is required for PNMT active site binding and catalysis, we have prepared and evaluated conformationally restricted phenylethanolamine analogues 8-10. The folded phenylethanolamine derivative 4-hydroxy-1,2,3,4-tetrahydroisoquinoline (8) is not a substrate and does not interact with the enzyme active site as an inhibitor as well as 1,2,3,4-tetrahydroisoquinoline (6). In the cyclic 2 aminotetralol systems, only cis-phenylethanolamine derivative 9 demonstrates activity as a PNMT substrate. The corresponding trans isomer 10 is not a substrate, in spite of enhanced active site interactions with respect to the parent analogue (2-aminotetralin, 4). Comparison of the inhibition constants for the folded (8,Ki = 175 microM) and extended (10,Ki = 9 microM) phenylethanolamine analogues strongly suggests that simultaneous binding of both the amino and hydroxyl functionalities to the PNMT active site requires an extended aminoethyl side chain conformation. PMID- 3336018 TI - N-(Retinoyl)amino acids. Synthesis and chemopreventive activity in vitro. AB - N-(all-trans-Retinoyl)amino acids were synthesized via all-trans-retinoyl chloride and an ester of the amino acid. The retinoyl derivatives of leucine, phenylalanine, alanine, tyrosine, and glutamic acid were prepared. The 13-cis retinoyl derivatives of leucine, phenylalanine, alanine, and glycine were prepared similarly from 13-cis-retinoic acid. In assays of the retinoylamino acids for reversal of squamous metaplasia in hamster trachea organ cultures, these compounds were less active than retinoic acid, but the leucine, alanine, and phenylalanine derivatives were similar in activity to several retinamides that suppress bladder carcinogenesis in vivo. Two of the retinoylamino acids, as well as two simple retinamides, were shown to be moderately cytotoxic to murine leukemia and human epidermoid carcinoma cells in culture. PMID- 3336017 TI - Cholecystokinin antagonists. Synthesis and biological evaluation of 4-substituted 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines. AB - A series of 4-substituted 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared by standard methodology. These compounds were tested in vitro as antagonists of the binding of [125I]cholecystokinin (CCK) to rat pancreas and guinea pig brain receptors and of the binding of [125I]gastrin to guinea pig gastric glands. All compounds proved to have greater affinity for the peripheral CCK receptor with some analogues having IC50's in the subnanomolar range. In vivo activity of selected compounds in mice is presented and the structure/activity profile of this class of benzodiazepines as CCK antagonists is discussed. PMID- 3336019 TI - Triazolines. 14. 1,2,3-Triazolines and triazoles, a new class of anticonvulsants. Drug design and structure-activity relationships. AB - Pioneering studies in our laboratories have led to the emergence of the delta 2 1,2,3-triazolines (4,5-dihydro-1H-1,2,3-triazoles) and the closely related 1H 1,2,3-triazoles as a unique family of anticonvulsant agents hitherto unknown. Unlike the traditional anticonvulsants, the dicarboximide moiety is absent from the traiazoline ring system. This paper examines the results of evaluation of several groups of 1-aryl-5-pyridyl-substituted triazolines and triazoles with particular reference to structure-activity relationships in each compound group as well as between compounds in the different groups and the 1,5-diaryl compounds. The Topliss manual approach for application fo the Hansch method is employed for the rational design of triazoline/triazole anticonvulsants. Anticonvulsant activity was determined, after intraperitoneal administration, in two standard seizure models in the mouse, the MES and scMet tests. Central nervous system toxicity was evaluated in the rotorod ataxia test. Analysis of structure-activity relationships using the Topliss scheme indicated a clear pi + sigma dependency in the 1-aryl-5-(4-pyridyl)triazolines while an adverse steric effect (Es) from 4-substitution appeared to be present in the 1-aryl-5-(3 pyridyl) compounds. A similar but strong steric effect dominated the structure activity pattern of the 1-aryl-5-(4-pyridyl)triazoles, although a sigma dependency was more evident in the 1-aryl-5-(3-pyridyl)- and the 1,5 diaryltriazole series. No significant activity was observed among the 1-aryl-5-(2 pyridyl)triazolines, and although the respective triazoles were active, the parameter dependency was not clearly defined. Similarly, the 1,5 diaryltriazolines, as a group, showed no pronounced anticonvulsant activity. However, replacement of the 5-aryl with a pyridyl group, particularly a 4 pyridyl, led to highly enhanced anticonvulsant activity. In addition, oxidation of triazolines with no anticonvulsant activity yielded, as a rule, triazoles that were active, which could be linked to their chemistry or structural conformation. The triazolines and triazoles evince anticonvulsant activity as a class and compare very well with the prototype antiepileptic drugs--ethosuximide, phenytoin, phenobarbital, valproate--in their anticonvulsant potency and minimal neurotoxicity. They have emerged as a new generation of anticonvulsant agents that show great promise as potentially useful antiepileptic drugs. PMID- 3336020 TI - (Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme (ACE). 1. Discovery of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1 oxohexyl]-L -proline a novel orally active inhibitor of ACE. AB - The synthesis of a series of orally active, phosphinyloxyacyl proline inhibitors of angiotensin converting enzyme (ACE) is described. The in vitro and in vivo ACE inhibitory activities are reported for each compound. The structure-activity relationship for this series of compounds in relation to the carboxyalkyl dipeptide ACE inhibitors as well as other types of hydroxyphosphinyl-containing ACE inhibitors (e.g., the corresponding nitrogen and carbon isosteres) is discussed. Within an isosteric series of phosphorus-containing inhibitors based on the lysylproline terminal dipeptide sequence, only the phosphonates (oxygen isosteres) show a high level of oral activity. Optimum potency and oral activity in the phosphonate series occurs with the (phenylbutyl)- and n-hexylphosphonate side chains. An aminobutyl side chain in the P1' residue is an absolute requirement for full expression of oral activity. The most potent of these compounds, 8b (SQ 29,852), has intravenous and oral activities superior in potency to those of captopril in the normotensive rat. PMID- 3336021 TI - Synthesis and antitumor activity of analogues of ifosfamide modified in the N-(2 chloroethyl) group. AB - A series of 3-(2-chloroethyl)-N-(2-X-ethyl)tetrahydro-2H-1,3,2-oxazaphosphorin -2 amine 2-oxides with various X substituents have been prepared by cyclization of racemic ifosfamide or its enantiomers with sodium hydride and subsequent treatment of intermediary products with hydrobromic acid, diethyl hydrogen phosphate, dibenzyl hydrogen phosphate, p-toluenesulfonic acid, and acetic acid. All of these compounds were tested in vivo against L 1210 lymphoid leukemia in mice. Only bromo analogue 13 and its enantiomers were effective, exceeding the activity of racemic ifosfamide and cyclophosphamide. The therapeutic index of the racemic 13 and its levorotatory enantiomer was about 1.7 times higher than that for ifosfamide and about 2.7 times higher than that for cyclophosphamide. PMID- 3336022 TI - Improved delivery through biological membranes. 32. Synthesis and biological activity of brain-targeted delivery systems for various estradiol derivatives. AB - Brain-targeted delivery systems based on the dihydropyridine in equilibrium pyridinium salt redox interconversion were synthesized for estradiol, estradiol 3 benzoate, and ethynylestradiol. Initial biological evaluation indicated that while all four compounds synthesized exerted central estrogenic activity as measured by serum LH suppression, only the delivery systems based on the 17 substituted estradiol and ethynylestradiol demonstrated prolonged action (greater than 12 days). The 17-(1-methyl-1,4-dihydronicotinic acid ester) of ethynylestradiol behaved in a similar manner to the previously described estradiol analogue in various assays. Tissue distribution studies in rats showed that administration of the ethynylestradiol derivative resulted in high sustained levels of the corresponding pyridinium salt in the central nervous system (CNS) while blood levels of the oxidized metabolite rapidly fell. The sustained brain levels were associated with a prolonged release of ethynylestradiol. By 24 h, posttreatment, no ethynylestradiol was found by HPLC in the blood while levels of over 20 ng/g of tissue were detected in the CNS. This enhanced central delivery gave a dose- and time-dependent LH suppression, which indicated a three- to fivefold increased potency compared with the corresponding estradiol derivative. PMID- 3336023 TI - Nitrosoureido nucleosides as potential inhibitors of nucleotide biosynthesis. AB - Several nitrosoureido nucleosides (3a, 3b, 5a, 7a, 7c, and 10a) designed as inhibitors of enzymes that metabolize pyrimidine nucleotides have been prepared and their chemical and biological properties studied. The methylnitrosoureas 3a and 3b were not significantly cytotoxic to H.Ep.-2 and L1210 cells in vitro but showed moderate activity in the P388 mouse leukemia screen (79% ILS for 3a and 56% ILS for 3b). The (chloroethyl)nitrosoureas 7a and 7c inhibited proliferation of L1210 cells, were cytotoxic to H.Ep.-2 cells, and demonstrated good activity against P388 in vivo (135% ILS with one 30-day survivor for 7a and 191% ILS with two 30-day survivors for 7c). Overnight exposure of L1210 cells to 7a and 7c resulted in cell enlargement accompanied by cell lysis. Macromolecular synthesis in enlarged cells, particularly RNA and protein synthesis, was markedly increased relative to that in untreated control cells. The half-lives of each of the nitrosoureas in pH 7 buffer was determined and compared with biological activity. PMID- 3336025 TI - Heterocyclic quinones with potential antitumor activity. 2. Synthesis and antitumor activity of some benzimidazole-4,7-dione derivatives. AB - A series of benzimidazole-4,7-dione derivatives, bearing substituents at positions 1, 2, 5, and 6 of the benzimidazole ring, has been synthesized and tested for antitumor activity in vivo on P388 leukemia. Some of the synthesized compounds show significant antitumor activity, associated with high toxicity, however. Compounds 7, 18, and 27 show the highest antitumor activity in this series, whereas 17, 19, and 22 are scarcely active. Some hypothetical biological precursors of these quinones are devoid of antitumor activity. Some structure activity relationships are discussed. PMID- 3336024 TI - Preparation and antischistosomal and antitumor activity of hycanthone and some of its congeners. Evidence for the mode of action of hycanthone. AB - The synthesis of a series of esters of hycanthone (HC) and 7-hydroxyhycanthone, their antitumor activity, and their antischistosomal effects on HC-sensitive and HC-resistant schistosomes are reported. Binding studies using tritium-labeled HC and hycanthone N-methylcarbamate (HNMC) with calf thymus DNA provided evidence that HNMC but not HC alkylated the DNA. Tritiated HNMC also bound to the DNA of intact HeLa cells exposed to the drug while very little tritiated HC bound to DNA under the same conditions. The mechanism proposed previously to account for the antischistosomal action of HC, namely, drug esterification followed by alkylation of DNA, applies also to the antitumor action of the drug as shown in Scheme I. PMID- 3336026 TI - Cholecystokinin antagonists. Synthesis and biological evaluation of 3-substituted 1,4-benzodiazepin-2-amines. PMID- 3336027 TI - N6-(arylalkyl)adenosines. Identification of N6-(9-fluorenylmethyl)adenosine as a highly potent agonist for the adenosine A2 receptor. AB - Several N6-(arylalkyl)adenosines related to N6-benzyladenosine were synthesized, and their A1 and A2 adenosine receptor binding affinities were determined. The annulated derivative N6-(1-naphthylmethyl)adenosine resulted in a very potent A2 agonist (A1 Ki = 24 nM, A2 Ki = 9.1 nM), whereas N6-(9 anthracenylmethyl)adenosine was virtually inactive (A1 Ki = 9,000 nM, A2 Ki = 29,000 nM). Interestingly, the structurally similar N6-(9 fluorenylmethyl)adenosine was the most potent A2 agonist reported to date, with a Ki of 4.9 nM in A2 binding and 5.1 nM in A1 binding. The homologues N6-9 fluorenyladenosine and N6-[2-(9-fluorenyl)ethyl]adenosine showed little or no activity at either adenosine receptor. Effects of these agents on heart rate and coronary flow in the isolated rat heart paralleled their A1 and A2 binding affinities, respectively. These data suggest that for high affinity at the A2 receptor a planar hydrophobic function at a certain distance and angle from the N6 nitrogen is required. PMID- 3336028 TI - Novel degradation products from the treatment of salinomycin and narasin with formic acid. AB - Salinomycin and narasin (4-methylsalinomycin) upon treatment with HCO2H furnish the known furanone fragment 3 and the complementary but rearranged fragments 1 and 2 respectively. The structure of 1 has been established by X-ray analysis. Upon being heated under reflux in PhMe, 1 undergoes the retrograde aldol reaction to furnish alpha, gamma-dimethyl-2-furanbutanal (4). The furan moiety of 1 is more resistant to electrophilic substitution than expected, but it can be acylated by highly reactive reagents such as (CF3CO)2O and AcOSO2Me. Compounds 1 and 2, the acetyl and trifluoracetyl derivatives of the former, and the reduction products thereof have no significant anticoccidial activity. PMID- 3336029 TI - Orally active hydroxamic acid inhibitors of leukotriene biosynthesis. PMID- 3336030 TI - Thyroid hormone analogues. Synthesis of 3'-substituted 3,5-diiodo-L-thyronines and quantitative structure-activity studies of in vitro and in vivo thyromimetic activities in rat liver and heart. AB - Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5 triiodo-L-thyronine (T3) have been synthesized by using established methods and by a new route involving manipulation of a 3'-formyl intermediate. In vitro hormone receptor binding (to intact nuclei) and in vivo thyromimetic activity (induction of mitochondrial 3-phosphoglycerate oxidoreductase, GPDH) were measured in rat liver and heart for these new analogues and for the 18 previously reported 3'-substituted 3,5-diiodo-L-thyronines. Analysis of the binding data using theoretical conformational and quantitative structure-affinity methods implies that the 3'-substituent recognition site on the thyroid hormone receptor is hydrophobic and limited in depth to the length of the natural iodo substituent, but has sufficient width to accommodate a phenyl or cyclohexyl group. Receptor binding is reduced by approximately 10-fold in 3'-acyl derivatives which form strong intramolecular acceptor hydrogen bonds with the adjacent 4'-hydroxyl. The compounds studied showed no differences in their relative affinities for heart and liver nuclei, suggesting that receptors in these tissues are similar. However, the relationships between thyromimetic activity (induction of GPDH) and nuclear binding showed some tissue differences. A high correlation between activity and binding is observed for full agonists in the heart, but an equally significant correlation for the liver data is only seen when 3'-substituent bulk (molar refractivity) is included in the analysis. These results suggest the possibility that differential tissue penetration or access to receptors may occur in vivo. PMID- 3336031 TI - [125I]-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane: an iodinated radioligand that specifically labels the agonist high-affinity state of 5-HT2 serotonin receptors. PMID- 3336032 TI - Chemical aspects of metoprolol metabolism. Asymmetric synthesis and absolute configuration of the 3-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-1-(isopropylamino)-2 propanols , the diastereomeric benzylic hydroxylation metabolites. AB - Asymmetric synthesis of 3-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-1 (isopropylamino)-2-propanol (2), the benzylic hydroxylation metabolite of metoprolol (1), is described, and the absolute configurations of the diastereoisomers were assigned. Ketone 3, prepared in a multistep synthesis, was reduced with a complex of (2S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol (9) and borane, yielding 2, with a ratio of 82:18 for the diastereomers. The absolute configurations 1'S,2S and 1'S,2R were assigned for the diastereomers formed in excess on the basis of reductions on closely related alkyl phenyl ketones and the circular dichroism spectrum. Derivatization of the 1'-hydroxyl group of oxazolidinone 10 with a chiral Mosher acid chloride and the use of an HPLC procedure to resolve the resulting esters enabled us to determine the metabolic product stereoselectivity for 2. In the presence of the rat liver microsomal fraction, the benzylic hydroxylation of 1 was highly product stereoselective favoring 1'R stereochemistry at the new asymmetric center in racemic 1 and in both enantiomers of 1. Determination of the stereochemistry of 2 will facilitate study of this polymorphically controlled metabolic process. PMID- 3336033 TI - Conformational preference for the binding of biaryl substrates and inhibitors to the active site of phenylethanolamine N-methyltransferase. AB - We have previously described regions of steric bulk tolerance in the aromatic ring binding site of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) for phenylethanolamine substrates and alpha-methylbenzylamine inhibitors. For bound substrates, this region is located in the vicinity of the para position of the aromatic ring, while for bound alpha-methylbenzylamine inhibitors, it is located in the region complementary to the meta position. In the present study, we sought to determine the preferred conformation of the biaryl portion of (m phenylphenyl)- and (p-phenylphenyl)ethanolamine (4 and 5, respectively) as well as for m-phenyl- and p-phenyl-alpha-methylbenzylamine (7 and 8, respectively) for PNMT active site interactions. Planar derivatives of 4, 5, 7, and 8 were obtained through the synthesis of 2-(1-fluorenyl)-2-hydroxyethylamine (9), 2-(2-fluorenyl) 2-hydroxyethylamine (10), 1-(1-fluorenyl)ethylamine (11), and 1-(2 fluorenyl)ethylamine (12). The four fluorene derivatives were examined for in vitro activity as substrates and inhibitors of the PNMT-catalyzed reaction. As in the case of 4, 5, 7, and 8, we have observed a positional preference for the alkylamine side chain with respect to the biphenyl skeleton present in 9-12. Thus, fluorenylethanolamine 10 ("p-biphenyl") displays a Michaelis constant (Km = 26 microM) that is approximately 10 times lower than that for 9 ("m-biphenyl", Km = 297 microM); in the alpha-methylbenzylamine inhibitors, fluorenyl derivative 11 ("m-biphenyl", Ki = 4.14 microM) is approximately 40 times better than 12 ("p biphenyl", Ki = 185 microM) for in vitro inhibition of PNMT. In each case, conformational restriction of the biaryl system present in 4, 5, 7, and 8, such that the aromatic rings are coplanar, resulted in enhanced affinity for the PNMT active site. Thus, conformational restriction of ethanolamine 5 (Km = 82 microM) as in 10 (Km = 26 microM) and alpha-methylbenzylamine 7 (Ki = 89 microM) as in 11 (Ki = 4.14 microM) leads, in each case, to a stronger enzyme-ligand dissociable complex. These results, in conjunction with others from these laboratories, indicate that the PNMT active site beyond the zone that interacts with the central aromatic ring portion of phenylethanolamine substrates and alpha methylbenzylamine inhibitors is essentially a flat, hydrophobic pocket. PMID- 3336034 TI - Substituted 1,3,4-thiadiazoles with anticonvulsant activity. 4. Amidines. AB - Two different structural types of 2-aryl-1,3,4-thiadiazole amidines were synthesized and evaluated for anticonvulsant activity. Enhancement of the inherent anticonvulsant activity therein and separation of this activity from the accompanying sedative action of these compounds were attempted. The most potent compounds occurred in the 2-(trifluoromethyl)phenyl series of type 3 amidines, but they also possessed a relatively high level of neurotoxicity and sedation as demonstrated in the rotorod test. PMID- 3336035 TI - Ring-substituted [1,2-bis(4-hydroxyphenyl)ethylenediamine]dichloroplatinum (II) complexes: compounds with a selective effect on the hormone-dependent mammary carcinoma. AB - [1,2-Bis(4-hydroxyphenyl)ethylenediamine]dichloroplatinum (II) complexes with one substituent in the 2-position (CH3, CF3, F, Cl, Br, I: meso- and d,l-1-PtCl2, meso-(3-5)-PtCl2, meso-(7 and 8)-PtCl2) or two substituents in the 2,6-positions (CH3, Cl: meso-2-PtCl2, meso- and d,l-6-PtCl2) in both benzene rings were synthesized and tested for estrogenic and cytotoxic activities. Two complexes (meso-6-PtCl2 and meso-7-PtCl2) possess both effects. In comparative tests on estrogen receptor positive and negative mammary tumors in cell culture (MCF 7, ER+ and MDA-MB 231, ER-) and in animals (MXT, ER+ and MXT, ER-, mouse), meso-6 PtCl2 shows a selective effect on the estrogen receptor positive mammary carcinoma. A further increase of efficacy was achieved with the water-soluble (sulfato)platinum(II) derivative (meso-6-PtSO4). On the DMBA-induced hormone dependent mammary carcinoma of the SD rat, meso-6-PtSO4 is significantly more active than its ligand (meso-6) and cisplatin. PMID- 3336036 TI - New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure activity relationships. AB - (p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD4-induced smooth muscle contraction on guinea pig ileum and LTC4-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C4 and D4. Among both series, ONO-RS-347 (18k) and ONO-RS-411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed. PMID- 3336038 TI - Comparison of performances of students in programs at LSU Medical School in Shreveport. AB - The purpose of the study reported here was to evaluate the performance of graduates of the accelerated six-year (combined B.S.-M.D. degree) program and compare it with that of graduates following the regular curriculum at the Louisiana State University School of Medicine in Shreveport. Cumulative medical school grade-point averages, scores on the Federation Licensing Examination, and failure rates for the two groups were compared; by these criteria, the six-year graduates performed adequately but not as well as expected from their high school credentials (the basis for their entry into the accelerated program). Advantages and disadvantages of the six-year program are discussed with respect to the students, the medical school, and the undergraduate college of LSU at Shreveport. PMID- 3336037 TI - N,N-Dialkylated monophenolic trans-2-phenylcyclopropylamines: novel central 5 hydroxytryptamine receptor agonists. AB - N,N-Dialkylated monophenolic derivatives of trans-2-phenylcyclopropylamine were synthesized and tested for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor stimulating activity by use of a biochemical test method in rats. A hydroxy substituent in the 2- or 3-position of the phenyl ring was required for 5 HT-receptor stimulation. N,N-Diethyl or N,N-di-n-propyl substitution gave the most potent 5-HT-receptor agonists. The 4-hydroxy and 3,4-dihydroxy derivatives of trans-2-phenyl-N,N-di-n-propylcyclopropylamine were inactive at central DA and 5-HT receptors. In contrast, the corresponding 3-hydroxy derivative 18 and some of its derivatives weakly affected both DA and NE synthesis. Two of the most potent 5-HT-receptor agonists, trans-2-(2-hydroxyphenyl)-N,N-di-n propylcyclopropylamine (8) and the 3-hydroxy isomer 18 were resolved into the enantiomers. The 1R,2S enantiomers of 8 and 18 displayed 5-HT activity, while the 1S,2R enantiomers were inactive. Compound (1R,2S)-18, but not (1R,2S)-8, weakly affected rat brain DA and NE synthesis. PMID- 3336039 TI - Student evaluation of accelerated program at the University of Miami. AB - The University of Miami School of Medicine has an accelerated, six-year B.S.-M.D. program called the Honors Program in Medicine (HPM). In 1985 the HPM and traditional program students were surveyed at the end of their first year in medical school regarding their opinions about accelerated medical education. Eighty-seven percent of the traditional students felt that HPM students had ability equal to that of the average medical student (that is, neither more nor less ability), but 41 percent felt that the HPM students were less mature than the average class member. The traditional students felt the HPM students were required to follow a rigid collegiate curriculum (76 percent) and had an inadequate nonscience background (68 percent) and that the HPM would negatively affect both the future professional competence of HPM participants (59 percent) and the medical profession (34 percent). A larger percentage of the HPM than the traditional students (63 versus 48 percent) reported earning more than a minor in nonscience subjects, and fewer HPM than traditional students (9 versus 36 percent) felt that pressure to maintain a high grade-point average limited their selection of college courses. The HPM students felt that they were well prepared for medical school academically (82 percent) and emotionally (91 percent). The HPM students excelled academically in college and in the preclinical curriculum. PMID- 3336040 TI - Combined B.S.-M.D. programs: time for a change? PMID- 3336041 TI - An interim report on the MCAT Essay Pilot Project. AB - Results from four pilot administrations of the Medical College Admission Test essay question are reported. Analyses focused on (a) the performance characteristics of sample groups differentiated by gender, size of hometown, race/ethnicity, and dominant language; (b) the relationships between essay scores and academic/demographic characteristics; and (c) the reliability of one 45 minute versus two 30-minute essays. No differences were found for examinees grouped by gender and size of home community. Mean differences among the racial/ethnic groups were explained largely by reading level differences. Differences in essay performance by language group were large and unexplained by reading level differences. No relationship was found between the essay score and the academic/demographic characteristics. Reliability estimates for two 30-minute essays were higher than for one 45-minute essay; however, the 30-minute period yielded writing of poorer quality. Test-retest reliabilities for the 45-minute topics will remain the focus of future studies as will performance by examinees for whom English is a second language. The impact of the essay on the selection process will also be assessed. PMID- 3336042 TI - Types of medical writing and teaching of writing in U.S. medical schools. AB - U.S. medical schools were surveyed to determine which types of medical writing are most important for physicians, house officers, and medical students to learn and whether such types are formally taught. According to the responding schools, the five most important types were: write-up of the patient history and physical examination, progress note and discharge summary (tied), peer-reviewed published paper (of either clinical or laboratory research), and grant proposal. Certain types, however, were considered more important for some categories of physicians and trainees than others. Although these major types of writing represent complex and diverse writing tasks, they are not taught extensively in medical schools or thoroughly explained in the literature on medical writing. PMID- 3336043 TI - Medical student's access to information and resources for the residency selection process. AB - In the study reported here, the authors analyzed senior medical students' attitudes regarding the availability of information and resources pertaining to the residency selection process. Results of a nationwide survey of students showed that when the students had access to information from medical professionals (that is, faculty members, deans, house staff physicians), they felt they had greater access to information than did students who made greater use of other sources (official directories, classmates and the "grapevine"). Furthermore, the findings suggest that greater availability of information from medical professionals was related to higher levels of overall satisfaction with the residency match. While no evidence is presented that demonstrates that medical school faculty members and administrators were unwilling to devote attention to any particular group of students, the data suggest that these professionals provided information regarding the residency selection process more often to medical students at high-prestige schools, students who chose high prestige specialties, and students who perceived themselves as having high class rank than to other students. Also, students in publicly supported schools felt the cost of travel for interviews to be more burdensome than did the students in private schools. PMID- 3336044 TI - Patterns of psychoactive drug prescriptions by house officers for nonpatients. AB - Substance abuse may be an occupational hazard for physicians, yet the mechanisms of this hazard remain obscure. The present authors tested the hypothesis that a potential source of psychoactive drugs for the physician trainees and other health professionals is prescription writing by house officers. Furthermore, the hypothesis was advanced that house officers may write significant numbers of psychoactive prescriptions for their family members and friends. Of 565 house officers at a medical center, 339 responded to a questionnaire designed to determine the number of prescriptions each had written for nonpatients in the previous eight months for several categories of psychoactive drugs. The largest number of such prescriptions was written for family members and friends, and the second largest number was for fellow house officers. Narcotics were the most frequently prescribed psychoactive drugs. When compared with their representation in the sample, first-year residents and residents in surgery and surgical subspecialties wrote significantly more psychoactive drug prescriptions than other residents. Implications of these findings for residents are discussed. PMID- 3336045 TI - A program to teach house calls for the elderly to fourth-year medical students. AB - The authors report on the development, implementation, and evaluation of a curriculum to teach house calls for the elderly to fourth-year medical students. A faculty committee drew up a statement of philosophy: developed attitude, knowledge, and skill objectives: and specified required educational experiences for the curriculum. which was incorporated into a required eight-week rotation in ambulatory medicine. In 1985 and 1986, 18 students completed the new curriculum at three different clinic sites and made a total of 167 documented house calls. Prerotation and postrotation measurement of the students' attitudes documented a significantly (p less than .003) more favorable attitude toward house calls after completion of the curriculum. The students further indicated that they were more likely after the curriculum than before it to provide house calls as part of their future medical practice. The students' evaluation of the curriculum provided information on the relative effectiveness of teaching strategies used in the curriculum and documented the success of the curriculum in transmitting knowledge about the homebound elderly. PMID- 3336046 TI - Basic science course grades as predictors of performance on the NBME Part I examination. PMID- 3336047 TI - The effect of human dissection on first-year students and implications for the doctor-patient relationship. PMID- 3336048 TI - Effect of required reading in a surgical clerkship on performance on the NBME surgery examination. PMID- 3336050 TI - A review of contact lens induced giant papillary conjunctivitis. PMID- 3336049 TI - Evaluation of Gannon-Hahnemann Program to provide family physicians for underserved area. AB - The Gannon-Hahnemann Family Medicine Program is a combined B.S.-M.D. program designed to provide family practitioners to northwest Pennsylvania, a medically underserved area. The first six graduating classes (1981 through 1986) of the combined six-year curriculum contained 81 students. These students completed two years of undergraduate education at Gannon University, Erie, Pennsylvania, and four years at Hahnemann University School of Medicine. The students were required to complete the clinical rotations of their final year of medical school in Erie, and one of the rotations had to be family practice. Of the 81 combined-program graduates, 24 (29.6 percent) initially selected family practice residencies, while only 5.2 percent of the regular admission Hahnemann students selected family practice. Of these 24 graduates, 13 completed family practice residencies, and six of those chose to practice in northwest Pennsylvania. Nine graduates remained in family practice training. PMID- 3336051 TI - A discussion of prism therapy for strabismus. PMID- 3336052 TI - Attachment for the Bausch & Lomb keratometer in pediatrics. PMID- 3336053 TI - A survey of parental understanding of strabismus. PMID- 3336054 TI - Breakthroughs in lens design and care. PMID- 3336055 TI - Toxicity of an acute dose of agent VX and other organophosphorus esters in the chicken. AB - The neurotoxicities of single doses of a chemical warfare agent VX [phosphonothioic acid, methyl-S-(2-[bis(1-methylethyl)amino/ethyl) O-ethyl ester], a metabolite of the agricultural chemical parathion, paraoxon, PO (phosphonothioic acid, diethyl paranitrophenyl ester), and the known neuropathic agents DFP] phosphorofluoridic acid, bis(1-methylethyl) ester] and TOCP (phosphoric acid, tri-o-tolyl ester) were compared in the chicken. Single injections (subcutaneous, sc) of VX as high as 150 micrograms/kg (5 times the LD50, intramuscular, im) were tolerated by laying tens if atropine and 2 pralidoxime were used as antidotes before and immediately after injection. The 150 of VX for inhibition of chicken brain acetylcholinesterase was approximately 5 X 10(-10). Plasma acetylcholinesterase, but not butyrylcholinesterase, was depressed 2 h after injections of 2-20 micrograms VX/kg im without antidotes. Levels of plasma enzymes such as creatine kinase, indicative of tissue damage, were increased after exposure to both VX and PO. Injections of up to 150 micrograms/kg of VX with antidotes did not cause locomotor or histological signs of organophosphorus-induced delayed neuropathy, but single injections of 400 mg TOCP/kg did. PMID- 3336056 TI - Toxicity of repeated doses of organophosphorus esters in the chicken. AB - Hens were repeatedly exposed to paraoxon (PO, phosphonothioic acid, diethyl paranitrophenyl ester), the chemical warfare agent VX/phosphorofluoridic acid, methyl-S-(2-[bis(1-methylethyl)amino/ethyl)O-ethyl ester], or the neuropathic DFP [phosphorofluoridic acid, bis(1-methylethyl)ester] as evidence was sought for nerve or other tissue damage following long-term treatments at high dose levels. Thirty-day and 90-d trials were performed in which each bird was injected 3 or 5 times per week with atropine as protection, weighed, their eggs collected, and their blood enzymes (cholinesterases creatine kinase, and lactic dehydrogenase) and locomotion periodically examined. Muscle and brain enzymes were assayed at the end of the experiments. Doses of PO and VX were at or above LD50 levels. DFP doses were lowered with each run to estimate a no-observable-effect level for organophosphate-induced delayed-neuropathy (OPIDN). No abnormalities attributable to repeated exposures to either PO or VX were found, even though acute, short term symptoms of toxicity appeared after each injection. No evidence for OPIDN was obtained with repeated exposures to PO and VX under conditions where OPIDN was caused by DFP. Histological signs of OPIDN appeared in the spinal cord without gross symptoms of ataxia following repeated treatments of 25 mg/kg of DFP. The results of one experiment suggested that exposure to protective injections of atropine delays the appearance of the locomotor symptoms of the DFP induced neuropathy. PMID- 3336057 TI - 6-Ketoprostaglandin F1 alpha and thromboxane B2 in isolated, blood-perfused lungs from monocrotaline pyrrole-treated rats. AB - Monocrotaline pyrrole (MCTP) causes pulmonary vascular injury and pulmonary hypertension in rats. Although the mechanism by which MCTP causes pulmonary hypertension is unknown, vasoconstriction may play a role. Thromboxane (Tx) A2 is a vasoconstrictor released from platelets and other blood cells. Following treatment with MCTP in vivo, the release of stable metabolites of TxA2 and prostacyclin [TxB2 and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha), respectively] was determined in isolated lungs perfused with blood. Early in the development of pulmonary hypertension, the concentrations of TxB2 and 6-keto-PGF1 alpha in the effluent plasma of lungs from treated rats were not different from control rats. When pulmonary hypertension was well established, the concentration of TxB2 was higher in the effluent plasma of lungs from MCTP-treated rats, although the concentration of 6-keto-PGF1 alpha was not affected by treatment. PMID- 3336058 TI - Repression by sustained-release beta-glucuronidase inhibitors of chemical carcinogen-mediated induction of a marker oncofetal protein in rodents. AB - The degree of induction of an oncofetal protein marker in rodents by selected chemical carcinogens has been correlated with changes in carcinogenicity induced by dietary D-glucaro-1,4-lactone (GL) based anticarcinogens. These potent anticarcinogens may act to increase the clearance of carcinogens as glucuronides through the inhibition of beta-glucuronidase. The sustained-release forms are particularly effective, 1.5 mmol/kg of GL maintaining serum beta-glucuronidase activity at or below 50% for only 1 h, while an equivalent amount of calcium glucarate (CGT) maintained this level of inhibition for over 5 h. CGT or other sustained-release inhibitors, when fed to rodents during administration of carcinogens that undergo glucuronidation, caused a marked reduction in the induction of the marker protein. For those systems where other markers of carcinogenesis were also assessed, it was determined that the inhibition of marker-protein induction was quantitatively similar to both the inhibition of binding of the carcinogen to DNA and the subsequent induction of tumors in target organs. PMID- 3336059 TI - The effect of zinc on the dithiocarbamate-induced mobilization of cadmium deposits in mice. AB - In comparison with similar experiments in which no zinc acetate was used, the addition of small amounts of zinc acetate to sodium N-methyl-N dithiocarboxyglucamine produces a significant increase in the amount of cadmium mobilized from the liver and kidneys of mice loaded ip with 10 mg CdCl2.2.5H2O/kg 2 wk prior to the initiation of treatment. Neither treatment results in the transport of significant amounts of cadmium to the brain. The injection of zinc acetate alone did not produce this effect. Experiments in which zinc acetate in drinking water was administered to cadmium-loaded animals showed that the liver and kidney cadmium levels were significantly increased, presumably via zinc mediated processes in which cadmium from other organs was mobilized to the liver and kidneys. PMID- 3336060 TI - Pulmonary vascularity: radiographic considerations. AB - Distribution of pulmonary vascularity, as imaged on the routine chest radiograph, may be used as an accurate and sensitive indicator of underlying pathophysiologic change. The lungs, like most other human organ systems, have extensive reserve capability. Such reserves exist in terms of excess alveolar capacity in the pulmonary vascular bed to compensate for certain vascular alterations. This available vascular reserve is potentially available to compensate for situations in which there is an imbalance created between the size (capacity) of the vascular bed and the amount of blood (content) that it must accommodate. Such imbalances can result from decrease in the size of the vascular bed secondary to destruction or to normal physiologic response mechanisms or from an increase in the amount of blood coursing through the vascular bed. Either occurrence or combination of occurrences necessitates recruitment of available pulmonary vascular reserves. Recognition of this recruitment phenomenon and understanding of its underlying pathophysiologic significance enable relatively sophisticated diagnostic interpretation of the chest radiograph. PMID- 3336061 TI - Pulmonary hypertension: etiology and clinical evaluation. AB - Elevation of pulmonary arterial pressure may be secondary to many diseases of the lungs, chest wall, and heart. From a pathophysiologic viewpoint, pulmonary hypertension is secondary to vascular obstruction, vasoactivity, increased circulation, and passive forces. Clinically, the entities that result in secondary pulmonary hypertension present with a picture that identifies the primary disease. Patients with primary pulmonary hypertension may be difficult to identify. Pulmonary hypertension may present early with dyspnea and fatigue, while syncope and hemoptysis are late symptoms. In many instances, pulmonary hypertension can be diagnosed utilizing physical examination and noninvasive tests. Eventually, right heart catheterization is necessary to confirm the diagnosis and to monitor trials of therapy with vasodilators. Treatment may be specific (closure of a septal defect, thromboendarterectomy) or generic (vasodilators). These have been used recently for both secondary and primary pulmonary hypertension in an effort to reduce pulmonary vascular resistance, thereby decreasing right ventricular afterload and improving cardiac output and oxygen delivery. The success of these treatments has not been demonstrated. PMID- 3336062 TI - A case report of segmental bronchial atresia: radiologic evaluation including computed tomography and magnetic resonance imaging. AB - Bronchial atresia is a rare anomaly that characteristically presents with a pulmonary nodule and hyperinflation of the lung distal to the nodule. To make this diagnosis definitively, invasive studies have been required. Now with the combined use of computed tomography and magnetic resonance imaging, a diagnosis can be made without resorting to invasive techniques. This article describes a case of bronchial atresia illustrating the noninvasive approach. PMID- 3336063 TI - Simultaneous occurrence of anomalous cardiac and tracheal bronchi: a case study. AB - A rare case of a combination of an accessory cardiac bronchus and a right tracheal bronchus found incidentally is presented, together with a discussion of the anatomy, embryology, and possible clinical ramifications of these anomalies. The incidence of these anomalies occurring in 2,000 tomographic studies of the chest at University of South Alabama Medical Center is cited. PMID- 3336064 TI - Computed tomography and pathologic correlations of thymic lesions. AB - Computed tomographic and pathologic correlations of the thymus gland were assessed in 69 patients. The sensitivity of computed tomography (CT) for undifferentiated thymic pathology is 87.1%; the specificity is 85.7%. The sensitivity of CT for neoplasm or mass is 97.1%, the specificity is 97.1%. The sensitivity of CT for lymphoid follicular hyperplasia (LFH) is 71.4%, the specificity is 97.6%. Therefore, a normal-sized thymus gland on CT does not exclude LFH. Completely preserved fat planes between thymic mass and adjacent structures on CT usually indicate a benign (noninvasive) neoplasm; completely absent fat planes usually indicate a malignant (invasive) neoplasm; partially preserved fat planes are indeterminate in assessing invasiveness. CT is also useful in showing recurrence or remnants of thymic tissue in patients who have had a previous thymectomy. PMID- 3336065 TI - Chest radiographic abnormalities in Lennert's lymphoma. AB - In reviewing the medical records of ten patients with Lennert's lymphoma, we found chest radiographic abnormalities in five cases. Two cases had hilar and mediastinal adenopathy without associated parenchymal or pleural disease, and three cases had isolated pulmonary parenchymal abnormalities. In one patient, both the chest radiograph and the histologic findings, obtained by open lung biopsy, mimicked miliary granulomatous disease. This article emphasizes the need to be alert to this aggressive T-cell neoplasm, since its clinical course differs significantly from some of the diseases it tends to imitate. By being aware of the entity and by using thorough pathologic and immunopathologic techniques, difficult cases of Lennert's lymphoma can be successfully diagnosed. PMID- 3336066 TI - Isolation of bacteriophage T4 baseplate proteins P7 and P8 and in vitro formation of the P10/P7/P8 assembly intermediate. AB - Two bacteriophage T4 proteins, P7 and P8, which are components of the phage baseplate have been purified to apparent homogeneity. P7 and P8 are the protein products of T4 genes 7 and 8. A plasmid has been constructed which contains approximately 5 kilobases of T4 DNA, including genes 7 and 8, under the control of the tac promoter. Induction of Escherichia coli W3110iQ cells containing this plasmid resulted in the production of functional P7 and P8. Standard protein isolation procedures were used to purify both P7 and P8 from extracts of induced cells. In T4-infected cells, these two proteins and P10 interact in a strictly ordered sequential manner (P10 + P7----P10/P7,P10/P7 + P8----P10/P7/P8) to form an intermediate in the baseplate assembly pathway. The three purified proteins assembled in vitro to form a limited number of oligomeric species, as determined by nondenaturing gel electrophoresis. P10 and P7 interacted in vitro to form two assemblies with distinct electrophoretic mobilities, both containing P10 and P7. Addition of P8 to this mixture resulted in the disappearance of both P10/P7 species and the appearance of a single new assembly with a different electrophoretic mobility. These interactions occurred without the addition of any catalyst or cofactors. Isolated P11 appeared to add as predicted to the in vitro formed complexes without affecting the formation of the two P10/P7 or the single P10/P7/P8 intermediates. Interactions between P7 and P8 in the absence of P10 or interactions between P10 and P8 in the absence of P7 could not be detected. These data indicate that purified P10, P7, and P8 interact in vitro in a manner completely in accord with the published assembly pathway and thus establish a system for further study of the regulation of the formation of this assembly intermediate in vitro. PMID- 3336068 TI - Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines. AB - Clinical studies previously demonstrated that live influenza A virus vaccines derived by genetic reassortment from the mating of influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus with epidemic wild-type influenza A viruses are reproducibly safe, infectious, immunogenic, and efficacious in the prevention of illness caused by challenge with virulent wild-type virus. These influenza A reassortant virus vaccines also express the ca and temperature sensitivity (ts) phenotypes in vitro, but the genes of the ca virus parent which specify the ca, ts, and attenuation (att) phenotypes have not adequately been defined. To identify the genes associated with each of these phenotypes, we isolated six single-gene substitution reassortant viruses, each of which inherited only one RNA segment from the ca parent virus and the remaining seven RNA segments from the A/Korea/1/82 (H3N2) wild-type virus parent. These were evaluated in vitro for their ca and ts phenotypes and in ferrets, hamsters, and seronegative adult volunteers for the att phenotype. We found that the polymerase PA gene of the ca parent specifies the ca phenotype and that the PB2 and PB1 genes independently specify the ts phenotype. The PA, M, PB2, and PB1 genes of the ca donor virus each contribute to the att phenotype. The finding that four genes of the ca donor virus contribute to the att phenotype provides a partial explanation for the observed phenotypic stability of ca reassortant viruses following replication in humans. PMID- 3336067 TI - Distinctive properties of the hepatitis B virus envelope proteins. AB - Using recombinant adenoviral vectors, we expressed and characterized the large, middle, and major envelope proteins of hepatitis B virus (HBV). Cells infected with the recombinant adenovirus which contained the large envelope gene (HS1.HP) expressed predominantly large envelope and small but detectable quantities of middle (4%) and major (6%) envelope proteins in the cell lysate. No HBV envelope proteins were detected in the culture medium from HS1.HP-infected cells. Cells infected with recombinant adenovirus which contained the middle envelope gene (HS2.HP) expressed and secreted the middle and major envelope proteins in a molar ratio of 3:1. Cells infected with the recombinant adenovirus which contained the major envelope gene (HS.HP) expressed and secreted major envelope proteins. The HBV envelope proteins secreted by cells infected with either HS2.HP or HS.HP were assembled in 22-nm particles, as shown by velocity sedimentation rate determination, buoyant densities, and electron microscopy. Cells coinfected with a recombinant adenovirus which contained the large envelope gene and with either HS2.HP or HS.HP expressed similar quantities of the large, middle, and major envelope proteins in the cell lysates. Secretion of the major and middle envelope proteins was inhibited more than 95% by the presence of the large envelope proteins. These results suggest that differential biosynthesis, transport, and processing of the envelope proteins occur during HBV infection, allowing efficient assembly and secretion of virions and hepatitis B surface antigen particles. PMID- 3336069 TI - Adenovirus preterminal protein synthesized in COS cells from cloned DNA is active in DNA replication in vitro. AB - Replication of the DNA genome of human adenovirus serotype 2 requires three virus encoded proteins. Two of these proteins, the preterminal protein (pTP) and the adenovirus DNA polymerase, are transcribed from a single promoter at early times after virus infection. The mRNAs for these proteins share several exons, including one encoded near adenovirus genome coordinate 39. By using plasmids containing DNA fragments postulated to encode the various exons of pTP mRNA, the contributions of each exon to the synthesis of an active pTP have been measured. Only plasmids that contain both the open reading frame for pTP (genome coordinates 29.4 to 23.9) and the HindIII J fragment that contains the exon at genome coordinate 39 can express functional pTP. PMID- 3336070 TI - Uptake of reovirus serotype 1 by the lungs from the bloodstream is mediated by the viral hemagglutinin. AB - We used the mammalian reoviruses to determine the molecular basis of the clearance of a virus from the bloodstream by specific organs. Reovirus serotypes 1 (T1) and 3 (T3) were radiolabeled with [35S]methionine or 125I, and the viruses were injected intravenously into weanling rats. The distribution of radioactivity within the animals was determined at various times after the injection. Both viruses were cleared rapidly from the bloodstream and concentrated in different organs. Reovirus T1 was found predominantly in the lungs and liver, whereas T3 was found predominantly in the liver, with very little virus in the lungs. Using intertypic reassortants, we determined that the T1 S1 gene, which encodes the viral hemagglutinin (sigma 1 protein), is responsible for the difference in uptake of T1 and T3 by the lungs. The genetic mapping was extended by using several approaches. (i) T1 subjected to limited proteolytic digestion with chymotrypsin was cleared efficiently by the lungs despite the removal of sigma 3 and digestion of mu 1C to delta. (ii) Uptake of T1 by the lungs was totally inhibited by incubation of T1 with an anti-sigma 1 monoclonal antibody or its Fab fragment before injection. (iii) A reovirus T1 variant in the sigma 1 protein was poorly taken up by the lungs. These data indicate that clearance of reovirus from the bloodstream by the lungs is dependent on the presence of the T1 sigma 1 protein. PMID- 3336072 TI - Feminizing adrenocortical tumors in male patients: adenoma versus carcinoma. AB - We report a case of a feminizing adrenocortical adenoma in a 8-year-old boy and feminizing carcinoma in a 25-year-old man. Because diagnosis of adrenal malignancy in such tumors by histopathological criteria is not always conclusive, a clinicoradiological approach may be used in the evaluation. PMID- 3336071 TI - Isolation of an integrated provirus of Moloney murine leukemia virus with long terminal repeats in inverted orientation: integration utilizing two U3 sequences. AB - We have previously described the construction of a mutant of Moloney murine leukemia virus, in594-2, which carries a 2-base-pair insertion in the U5 region of the genome and is partially defective in forming the integrated proviral DNA. We have now recovered a cloned copy of an unusual provirus from rat cells infected with this mutant. The viral genome is flanked by long terminal repeats in inverted orientation, with U3 sequences joined to cellular DNA at both of the outer edges. In addition, the provirus is a recombinant, containing a segment of a VL30 element in inverted orientation in place of the Moloney murine leukemia virus env region. The recovery of this provirus indicates that two U3 regions can be used for viral integration and suggests that there may be no absolute requirement in the reaction for those U5 sequences outside the 13-base-pair inverted repeats. PMID- 3336073 TI - Renal parenchymal neurilemoma: a rare and unusual kidney tumor. AB - We report a case of a neurilemoma arising from the renal parenchyma. Renal neurilemoma is an extremely rare tumor, with only 5 cases previously reported. Because so little is known of its natural history and potential for malignancy we recommend radical nephrectomy as the treatment of choice. PMID- 3336074 TI - A new alternative treatment for entrapped stone basket in the distal ureter. AB - We describe an alternative method for the treatment of an entrapped stone basket. When efforts to remove an engaged stone through the intramural ureter met with marked resistance, the basket with the stone within it was advanced into the renal pelvis. Extracorporeal shock wave lithotripsy then was used to pulverize the stone, allowing successful removal of the basket. PMID- 3336075 TI - Castleman's disease: an unusual retroperitoneal mass. AB - Castleman's disease (angiofollicular lymph node hyperplasia) rarely presents as an isolated retroperitoneal mass radiographically indistinguishable from retroperitoneal malignancies. We report a case of the hyaline vascular variant of Castleman's disease presenting as a calcified pararenal mass. Computerized tomography and nuclear magnetic resonance imaging of this lesion are presented, and its clinical behavior and management are discussed. PMID- 3336076 TI - Vesicouterine fistula: a rare complication of cesarean section. AB - Vesicouterine fistula is a rare complication of cesarean section. Most patients present early postoperatively, while others are seen months later with urinary incontinence. Recurrent urinary infections, menstruation through the bladder (menouria), secondary infertility and amenorrhea are less common reasons for consultation. Although more than 100 such cases have been described, there have been few reports on fertility after surgical cure of the fistula. We report 4 cases of a vesicouterine fistula after cesarean section. The first patient was treated nonoperatively and the other 3 patients were treated surgically. Three patients had normal pregnancies after resolution of the problem. The clinical features, etiological factors and treatment modalities are discussed. PMID- 3336077 TI - Bladder neck obstruction secondary to Brunn's cyst. AB - A large solitary Brunn's cyst caused a ball-valve type of obstruction of the bladder neck in a 29-year-old man without endoscopic or histological evidence of bladder inflammation. Unroofing and drainage restored normal voiding. The histopathological features of Brunn's nests are reviewed. PMID- 3336078 TI - Acute acalculous cholecystitis after radical cystectomy. AB - We report 2 cases of acute acalculous cholecystitis after radical cystectomy and continent urinary diversion with a Kock reservoir and ileocecal bladder replacement, respectively. Early diagnosis is essential since the mortality is high with conservative treatment. Isotopic cholescintigraphy is an effective diagnostic test and cholecystectomy is the treatment of choice. PMID- 3336079 TI - Bacterial prostatitis: an unusual cause of total urinary incontinence and its surgical management. AB - A case of total urinary incontinence as a late sequela of bacterial prostatitis is reported. The etiology of the incontinence and its surgical management are discussed. The patient is continent and is gainfully employed. PMID- 3336080 TI - Re: Internal urethrotomy in girls and its impact on the urethral intrinsic and extrinsic continence mechanisms. PMID- 3336082 TI - Re: Suprapubic urethropexy. Management with a transvesical exposure. PMID- 3336081 TI - Re: A new, one-stage pedicled scrotal skin graft urethroplasty. PMID- 3336084 TI - Epididymitis and the acquired immunodeficiency syndrome. PMID- 3336083 TI - Re: The high incidence of benign testicular tumors. PMID- 3336086 TI - Re: Anesthetic induction trismus, more than a closed mouth problem. PMID- 3336085 TI - Re: Prognosis of untreated stage A1 prostatic carcinoma: a study of 94 cases with extended followup. PMID- 3336087 TI - Re: Considerations in the choice of sutures for wound closure of the genitourinary tract. PMID- 3336088 TI - An investigation into the role of ascorbic acid in renal calculogenesis in albino rats. AB - Neither stone nor calcium oxalate crystal deposition was observed in the kidneys of rats after oral ingestion of 60 mg. L-ascorbic acid daily for three months, although urinary excretion of stone inhibitors (magnesium and citrate) was decreased and oxalate increased. The highly acidic pH of urine and reduced calcium excretion might have prevented their deposition. PMID- 3336089 TI - Non-neuromuscular determinants of intraluminal urethral pressure in the female baboon: relative importance of vascular and nonvascular factors. AB - The female urethral sphincteric mechanism has both neuromuscular and non neuromuscular components. The latter component has several determinants, including the urethral mucosa, the connective tissue of the urethra and periurethra, and the submucosal vascular bed. This study was designed to characterize the non-neuromuscular component of the urethral pressure profile (UPP) by quantitating the relative contributions of its vascular and non-vascular determinants in four female baboons. Following minimization of the smooth muscle and striated muscle determinants (the neuromuscular component) with halothane and pancuronium bromide, UPPs were performed before and after aortic occlusion. It is concluded that vascular and non-vascular factors contribute nearly equally to the non-neuromuscularly generated portion of intraluminal urethral pressure. PMID- 3336090 TI - The effect of bacillus Calmette-Guerin on the urinary system of pigs. AB - An experimental study was conducted to determine the changes in structure and function of the pig kidney and renal pelvis following intrarenal infusion of bacillus Calmette-Guerin (BCG). Bilateral nephrostomy tubes were inserted in six pigs through a subcostal (flank) retroperitoneal approach. One week later, antegrade pyelograms and renal scans with hippuran I-131 were obtained. The left kidney was then infused weekly for six weeks with two ampules of BCG (Tice strain) dissolved in 75 cc of saline. The right kidney, serving as a control, was infused concomitantly with 75 cc of saline. On week 7, bilateral antegrade pyelograms and renal scans were repeated. Two pigs were sacrificed at four, eight and 12 weeks after completion of BCG therapy. In all pigs, antegrade pyelograms of the left kidney before BCG instillation were identical to those obtained after completion of treatment and to those of the saline infused kidneys. The isotope renal scan in five pigs showed no significant change in image appearance or relative renal plasma flow in the pre-treatment and post-treatment images. In one pig, there was a decrease in the relative clearance of hippuran in the saline infused kidney. In this kidney, an upper pole abscess was found. Microscopic examination of the renal cortex, medulla, pelvis and ureter of the BCG infused kidneys was normal and identical to the saline infused kidneys. The urothelium was intact and no inflammatory changes were noted in the renal cortex or medulla. These results show that direct infusion of BCG into the renal collecting system has no adverse effect on the structure and function of pig kidneys when followed one to three months after treatment. PMID- 3336091 TI - Relationship between perineal muscle contractions, penile tumescence, and penile rigidity during nocturnal erections. AB - The mechanism of penile erection and erectile dysfunction is still unclear and widely debated. The role of the perineal muscles in the erectile process, especially in changes in intracavernous pressure, is increasingly being studied on the hypothesis that perineal muscular contractions are essential to full penile rigidity. In a previous investigation we studied the correlation between voluntary perineal muscle contractions and intracavernous pressure during artificially induced erections. The purpose of the current study was to examine whether under normal conditions of nocturnal erection a similar relationship exists between the electromyographic activities of perineal muscles and changes in penile rigidity. Nocturnal penile recordings were made of seven volunteers with psychogenic erectile dysfunctions. During nocturnal erections simultaneous computerized recordings were made of penile tumescence, penile rigidity, and electromyographic activities of perineal muscles. The peaks for the three variables were reached simultaneously. The results of this study suggest the existence of two different physiologic phases: a vascular phase and a muscular phase. Furthermore, in cases of dysfunctions, specific diagnostic assessment and therapeutic management will be required for both penile tumescence and penile rigidity. PMID- 3336092 TI - Extracorporeal shock wave lithotripsy in traumatic quadriplegic patients: can it be safely performed without anesthesia? AB - A total of 5 traumatic quadriplegic patients underwent 10 extracorporeal shock wave lithotripsy treatments with either a local (bupivacaine 0.25 per cent) field block or no anesthesia. Significant intraoperative hypertension as determined by the anesthesiologist occurred in 2 patients and responded to intravenous hydralazine. The complete clinical syndrome of autonomic dysreflexia did not occur. Three patients are free of stones and 2 have insignificant residual caliceal fragments. Extracorporeal shock wave lithotripsy may be performed safely in traumatic quadriplegic patients without the added risk of general or regional anesthesia. It is recommended that during therapy these patients should be monitored closely by an anesthesiologist for the signs and symptoms of autonomic dysreflexia. PMID- 3336093 TI - The effects of various indwelling ureteral catheter materials on the normal canine ureter. AB - In an attempt to objectively evaluate the biocompatibility of materials commonly used for ureteral stenting, stent-catheters made of four different materials were placed randomly in 31 ureters of 19 mongrel dogs. Animals underwent urography at four weeks and were sacrificed at six weeks. Mild hydronephrosis was noted in eight instances, essentially unrelated to specific material. Silicone, C-flex and polyurethane stents caused a similar, mild degree of ureteral edema, but ureters stented with Silitek demonstrated fairly marked edema. Epithelial ulceration and erosion, often severe, occurred with all polyurethane stents, and rarely with the three other materials. All materials differed statistically from controls, and C flex caused less reaction overall than polyurethane, indicating differences in biocompatibility of the various materials which may be relevant to their use in patients undergoing long-term ureteral stenting. In practical terms, these suggest that certain materials, notably silicone and C-flex, are more suitable for ureteral stenting than others. PMID- 3336094 TI - The influence of urinary macromolecules on calcium oxalate monohydrate crystal growth. AB - The Constant Composition (CC) kinetics method has been used for studying the mineralization of calcium oxalate monohydrate (COM) at sustained supersaturations in the presence of pre-bladder urine and macromolecules isolated from normal urine and kidney and bladder stones. The method is especially sensitive for investigating the inhibitory activities of these urinary macromolecular components (UMMC) and matrix macromolecular components (MMMC) with a coefficient of variation in growth rate of approximately 2%. Significant COM mineral inhibition was observed in a wide molecular weight region of urine components. Urine removed directly from the kidney showed appreciable inhibitory activity towards COM crystallization. Normal urinary proteins and the dissolved precipitate resulting from urine centrifugation were fractionated by gel filtration. The resulting solutions were mostly COM mineralization inhibitors. Electrodialysis was utilized to isolate the MMMC (greater than 7000 d) of renal and bladder calculi. While these solutions inhibited COM crystallization, they were also found to be calcium binders as measured by the calcium electrode. PMID- 3336095 TI - ND: YAG nomogram dosimetry scale for the bladder. AB - Bowel perforation and damage to surrounding organs is probably the most significant risk with the use of Nd-YAG laser in the bladder. To prevent this unwanted damage, a nomogram dosimetry scale was developed by delivering different settings of laser energy via a cystoscope to 25 female pigs. One week following treatment, exploratory laparotomy and cystectomy were performed. Microscopic analysis of the depth of laser irradiation was accomplished. From this study it was learned that, although the greater the energy delivered, the deeper the tissue damage, this is not uniform. Pulsed energy produced a deeper effect than continuous energy. The use of 30 watts of either pulsed or continuous energy for no longer than 15 seconds (450 joules) or 10 watts of either form of energy for less than 30 seconds (300 joules) did not produce bowel perforation. Other different combinations of high number of watts or pulses translated into transmural necrosis of the bladder with or without perforation and with or without bowel injury. Other factors such as density, thickness, color and temperature of tissue, type and wave length of laser and optimal focusing played a significant role in the final outcome. Useful information for human clinical use may be extrapolated from this experimental model. PMID- 3336096 TI - Response of normal canine ureter to photodynamic therapy using a cylindrical fiber. AB - Photodynamic therapy (PDT) was performed utilizing a cylindrical optical fiber to determine feasibility of distal ureteral treatment on 10 study and two control NIH foxhounds. The study animals were administered three mg./kg. dihematoporphyrin ether (Photofrin II) intravenously followed 48 hours later by open cystotomy. One ureter was irradiated with 42 joules of 630 nm. light delivered by a 660 micron diameter optical fiber modified for cylindrical light distribution. Intravenous urography was performed both at three days and six weeks post PDT. Hydroureteronephrosis was revealed in one treated ureter and one untreated ureter. Mild dilatation of the ureter was noted by urography in another treated ureter and in one ureter that did not undergo light irradiation; no distal obstruction was revealed in either case by proximal infusion of saline or by histopathology. Nine of the 10 treated ureters were found to have either no abnormal pathology or only minimal lymphocytic infiltration. In this study, the normal ureter was shown to tolerate photodynamic therapy at energy densities equivalent to those used to effect tumor regression and the feasibility of using a cylindrical optical fiber for treatment of ureteral malignancies was confirmed. PMID- 3336097 TI - Angiomyolipoma: clinical metamorphosis and concepts for management. AB - In 10 years the diagnosis of renal angiomyolipoma was made in 44 patients (female to-male ratio 8:1) at our institution; 4 cases were associated with tuberous sclerosis. Of these patients 29 underwent surgical exploration because of a renal mass; 11 patients with renal masses that were consistent with angiomyolipoma radiologically have not undergone exploration. Of the 4 patients with and the 29 patients without tuberous sclerosis 1 (25 per cent) and 2 (7 per cent), respectively, had renal cell cancer in association with angiomyolipoma. Metachronous involvement of the contralateral kidney has not been noted in any of our patients who underwent nephrectomy for unilateral involvement, nor has there been progression of the contralateral lesion in 3 patients with bilateral disease without tuberous sclerosis during a followup of about 6 years. Furthermore, we have not noted progression of lesions in the 11 patients under observation for a mean followup of almost 3 years. We recommend elective exploration and a renal preserving operation when possible, not only for patients with pain and hemorrhage but also for the complex multiple lesions occasionally seen in patients who do not have tuberous sclerosis. Lesions associated with tuberous sclerosis require surgical intervention only when they become symptomatic or enlarge silently. PMID- 3336099 TI - Endopyelotomy for primary repair of ureteropelvic junction obstruction. AB - A total of 12 patients underwent primary repair of ureteropelvic junction obstruction between November 1, 1985 and December 31, 1986. Ten patients underwent percutaneous incision of the ureteropelvic junction (endopyelotomy) as the initial effort to correct the obstruction. Two patients with ureteropelvic junction obstruction associated with an aberrant lower pole renal artery underwent dismembered pyeloplasty (Anderson-Hynes) via a flank incision. Of the 10 patients who underwent endopyelotomy 8 (80 per cent) have shown radiographic improvement. Radiographic stability of the obstructed ureteropelvic junction was demonstrated in the remaining 2 patients. No patient exhibited evidence of increased obstruction or decreased renal function. No patient required prolonged or rehospitalization for complications, and none required additional endoscopic or surgical procedures. All patients have remained clinically well after the initial release from the hospital. PMID- 3336098 TI - Resection of large inferior vena caval thrombi from renal cell carcinoma with the use of circulatory arrest. AB - Removal of a large extension of renal cell carcinoma into the inferior vena cava can be a difficult operation. Circulatory arrest is an operative technique that recently has been used to assist in resection of tumors that extend into the vena cava above the level of the hepatic veins. At our clinic 18 patients were operated on with the intent of using circulatory arrest during radical nephrectomy and inferior vena caval thrombectomy. Of the 18 patients 13 ultimately underwent this procedure, since the remaining 5 had unresectable tumors. One patient died intraoperatively of an adverse reaction to protamine after technically successful removal of the tumor and thrombus. Resection was successful in 12 patients and 9 remained free of disease with short followup. We believe that the addition of circulatory arrest during resection of a large inferior vena caval thrombus allows for an opportunity to resect the tumor in a controlled situation that reduces the potential for sudden massive blood loss or a major vascular injury, and ultimately makes the operation safer. PMID- 3336100 TI - Ureteral stone manipulation before extracorporeal shock wave lithotripsy. AB - We randomized 75 patients with solitary ureteral calculi that could not be dislodged by ureteral catheterization to receive instillation of saline, 2 per cent lidocaine viscous solution or dilute surgical lubricant before repeat stone manipulation with ureteral catheters. Of the stones irrigated with saline 76 per cent were returned to the pelvis along with 60 per cent of the lidocaine group and 48 per cent of the surgical lubricant treated stones. There was no statistical significance among the 3 groups. The success rates for upper, mid and lower ureteral stones were 80, 54 and 30 per cent, respectively. Of stones 0.5 cm. or less and between 0.6 and 1.0 cm. 77 and 72 per cent, respectively, were manipulated successfully but only 38 per cent of the stones larger than 1.0 cm. could be dislodged. Extracorporeal shock wave lithotripsy was successful in treating pelvic and ureteral stones, although higher kilovolt settings and additional shocks were necessary to fragment the ureteral stones completely. Percutaneous nephrostomy or ureteral meatotomy was required in 10 per cent of the patients with impacted ureteral stones following in situ extracorporeal shock wave lithotripsy but in only 4 per cent of the patients with stones successfully returned to the pelvis. Of the ureteral stones 17 per cent were treated with repeat extracorporeal shock wave lithotripsy. No patient with pelvic stones required repeat treatment. Retrograde manipulation of ureteral stones is an effective adjunctive procedure before extracorporeal shock wave lithotripsy. PMID- 3336101 TI - The ileal neobladder. AB - An ileal neobladder for total bladder replacement was created in 11 patients. To achieve a low pressure system, disruption of directional bowel peristalsis with a longitudinal incision at the antimesenteric border of a 70 cm. ileal segment is performed. A spherical pouch, the neobladder, is fashioned and anastomosed to the urethra. The ureters are implanted according to the method of Le Duc and Camey. Videourodynamic studies during various postoperative phases demonstrate this neobladder to be a urinary reservoir with a capacity approximating that of a normal bladder, good compliance during filling by maintaining pressure lower than 30 cm. water and no reflux. Of the 11 patients with the neobladder 8 are completely dry day and night, while 3 have grade I stress incontinence. All 11 patients had recognizable sensations of bladder distension closely simulating those of normal bladders. The use of this ileal neobladder in male patients undergoing radical cystectomy offers an alternative free of a stoma to urinary diversion, resulting in a highly compliant, low pressure bladder. PMID- 3336102 TI - Mechanisms of injury, patterns of extravasation and management of extraperitoneal bladder rupture due to blunt trauma. AB - During the last 7 years we have managed more than 100 cases of bladder rupture, the majority owing to blunt trauma. Of these ruptures 62 were extraperitoneal, including 59 (95 per cent) with associated pelvic fractures. Twelve patients had an associated urethral injury and 5 had a concomitant intraperitoneal bladder rupture. Complex injuries with extravasation outside the confines of the perivesical space were noted in 42 per cent of the patients. Extravasation extended into the scrotum, thigh, anterior abdominal wall and penis, and through the obturator foramen. The 41 patients who were treated with catheter drainage alone did well. PMID- 3336103 TI - 42 months of experience with the Mentor inflatable penile prosthesis. AB - The Mentor inflatable penile prosthesis is a hydraulic device that was introduced in May 1983 for the treatment of erectile dysfunction. Since its introduction further technical modifications and improvements have been made on the product. From the onset the reliability, function and cosmetic effect of this physiological device have been excellent. The modifications have served to improve the ease of operation and to increase further the reliability as demonstrated by our progressive decrease in the incidence of mechanical failures. From May 1983 to November 1986 we implanted 137 Mentor inflatable penile prostheses. Our over-all mechanical failure rate was 7.3 per cent. As a result of the modifications, however, the mechanical failure rate decreased to 3.1 per cent during the last 38 months of that period when 129 (94 per cent) of the prostheses were implanted, and during the last 24 months of that period when 86 (63 per cent) of the prostheses were implanted the mechanical failure rate was only 1.2 per cent. PMID- 3336104 TI - Late hematogenous infection of penile prostheses. AB - Late deep wound infection caused by hematogenous bacterial spread from a remote focus is a rare but disastrous complication of prosthetic devices. Six patients with probable late hematogenous infection are described. The initial implantation was free of contamination and infection, and a long functional interval ensued. A febrile process associated with a painful, swollen penis followed a probable remote infection source that was not covered with prophylactic antibiotics. All prostheses required removal. Prophylactic antibiotics may prevent these late hematogenous infections. PMID- 3336105 TI - Vasovasostomy with use of medical needle as a support. AB - Between May 1981 and December 1985 we performed vasovasostomy using a needle as a support in 43 patients who had undergone vasectomy for family planning. The operation is simple with little surgical trauma and few complications. All 39 patients who underwent semen analysis had return of spermatozoa. Pregnancy resulted in 27 of 34 patients (79.41 per cent) who attempted conception. The results were satisfactory. The procedure is described, and the complication and success rates are analyzed. PMID- 3336107 TI - Innovation and excellence: Ramon Guiteras lecture, American Urological Association 1987. PMID- 3336106 TI - Quantitative bacterial tissue cultures from 209 prostatectomy specimens: findings and implications. AB - To define the prevalence of prostatic bacterial infection or colonization, tissue from 209 patients undergoing prostatectomy (204 transurethral and 5 suprapubic) was submitted for quantitative bacterial tissue cultures. Tissue from 44 patients (21 per cent) yielded positive, single organism bacterial growth. In an attempt to identify preoperatively this patient subgroup, multiple preoperative and intraoperative variables were examined. Although the presence of a preoperative indwelling catheter was associated with positive prostate cultures, only 34 per cent (24 of 70) of the patients with preoperative catheters had positive prostate cultures. Of the 44 patients with positive prostate cultures 36 (82 per cent) had sterile urine cultures documented preoperatively, all urine specimens having been obtained in the absence of antibiotics. The data support a significant prevalence (21 per cent or more) of prostatic infection in patients undergoing prostatic surgery for obstructive symptoms and an apparent paucity of reliable indicators by which to identify preoperatively this patient population. PMID- 3336108 TI - Stage A versus stage B adenocarcinoma of the prostate: morphological comparison and biological significance. AB - Morphological features in radical prostatectomy specimens from 11 stage A and 73 stage B prostatic carcinomas were compared by mapping of tumor locations, and determinations of cancer volumes and histological patterns. Small stage A cancers were located anteromedially, while small stage B carcinomas were concentrated against the posterior capsule at the rectal surface. Small stage A carcinomas commonly invaded the anterior fibromuscular stroma and benign prostatic hyperplasia nodules, features that were uncommon even in large stage B tumors. Stage A cancers often appeared to arise within benign prostatic hyperplasia nodules and had a distinctive histological appearance. Even when large, stage A carcinomas tended not to spread close to the rectal surface of the gland. Stages A and B cancers spanned a roughly comparable volume range, and both showed progressive dedifferentiation with increasing volume. It is proposed that stages A and B cancers are biologically similar malignancies, distinguished only by their site of origin. Prognosis for patients with stage A carcinoma probably is closely related to tumor volume and dedifferentiation, features that are not reliably estimated in tissue samples removed at operation for benign prostatic hyperplasia. PMID- 3336109 TI - Effect of silver oxide/trichloroisocyanuric acid antimicrobial urinary drainage system on catheter-associated bacteriuria. AB - We assessed the efficacy of silver oxide coating of the indwelling urethral catheter and catheter adapter, and instillation of trichloroisocyanuric acid into the urinary drainage bag in the prevention of catheter-associated bacteriuria in a prospective and randomized study of 74 patients. Bacteriuria was documented in 29 of the 74 patients (39 per cent). There was a significant difference between the attack rates, with 11 of 41 patients (27 per cent) in the test group and 18 of 33 (55 per cent) in the control group having bacteriuria (p equals 0.02) after a median time to bacteriuria of 36 and 8 days, respectively (p equals 0.01). Urethral meatal colonization was implicated as the source of bladder bacteriuria in 12 of 18 patients (67 per cent) in the control group and 5 of 11 (45 per cent) in the test group. Trichloroisocyanuric acid significantly reduced drainage bag contamination but bag contamination with the same microorganism responsible for bacteriuria preceded infection in only 2 of the 29 patients (7 per cent), 1 in each group. Patients who received systemic antimicrobial agents acquired bacteriuria less frequently than those who did not. The apparent protective effect of systemic antimicrobials was strongest during the first 4 days of catheterization. The data indicate that episodes of bacteriuria arising from the urethral meatus are common among catheterized patients and that the antimicrobial catheter is effective in reducing the incidence of catheter-associated bacteriuria. PMID- 3336110 TI - The association of neuroblastoma with myoclonic encephalopathy of infants: the use of magnetic resonance as an imaging modality. AB - The association of neural crest tumors with myoclonic encephalopathy of infants has been well described. Since these tumors often are clinically occult the diagnostic modalities used to identify these lesions need to be sensitive. We describe a child with neuroblastoma associated with infantile myoclonic encephalopathy in whom magnetic resonance imaging identified the lesion while other techniques were unable to demonstrate a mass clearly. Magnetic resonance imaging should be considered as a diagnostic modality when adrenal lesions are suspected but not apparent with other imaging techniques. PMID- 3336111 TI - The prophylactic use of clean intermittent catheterization in the treatment of infants and young children with myelomeningocele and neurogenic bladder dysfunction. AB - To examine the hypothesis that the prophylactic use of clean intermittent catheterization can prevent urinary tract deterioration in infants and young children with myelomeningocele a prospective controlled study was performed on 24 patients. Preliminary results indicate that more than 50 per cent of the patients with bladder sphincter incoordination managed by self-voiding had urinary tract deterioration. In contrast, in only 10 per cent of the patients treated prophylactically with clean intermittent catheterization did deterioration occur. We conclude that when bladder sphincter incoordination is diagnosed in children with myelomeningocele they are at a high risk for the development of future urinary tract injury. The prophylactic use of clean intermittent catheterization can actually prevent this deterioration and its use in this manner is recommended. PMID- 3336113 TI - Paratesticular dermoid cyst in 6-month-old infant. AB - We describe a 6-month-old male infant with a dermoid cyst of the left paratesticular region. To our knowledge, this represents the youngest patient reported with this rare benign teratoma. We advocate enucleation for this particular type of teratoma based on referenced histopathological criteria. PMID- 3336112 TI - Pronounced dilatation of Cowper's gland duct manifest as a perineal mass: a recommendation for management. AB - It is generally accepted that large dilatations of Cowper's gland duct presenting as a perineal mass should be managed by perineal excision. Experience with such a case suggests that if the lesion also is visualized endoscopically, transurethral unroofing should be the initial choice of management. PMID- 3336115 TI - Presidential address: a philosophy of medical practice. PMID- 3336114 TI - Massive retroperitoneal hemorrhage owing to a ruptured adrenal cyst. AB - We report a rare case of massive retroperitoneal hemorrhage owing to rupture of an adrenal cyst after blunt abdominal trauma. A large retroperitoneal hematoma was evacuated and subtotal adrenalectomy was performed. Convalescence was uneventful. Histology revealed an endothelial-lined adrenal cyst suggesting a vascular or lymphatic etiology. PMID- 3336116 TI - Expression of genes for platelet-derived growth factor in adult human venous endothelium. A possible non-platelet-dependent cause of intimal hyperplasia in vein grafts and perianastomotic areas of vascular prostheses. AB - Neointimal fibromuscular hyperplasia (NFH) in vein grafts and perianastomotic zones of vascular prostheses has been attributed to the effects of platelet derived growth factor (PDGF) released by platelets interacting with bypass conduits. But inhibition of platelet aggregation often fails to prevent NFH, and recurrent growth of intact, platelet-free endothelium over perianastomotic areas where NFH occurs is inconsistent with the concept of sustained PDGF release from platelets causing NFH progression at late times after surgical procedures. Cultured bovine aortic endothelial cells (ECs) and human umbilical vein ECs have been shown to release a PDGF-like molecule. We report that confluent cultured fourth passage adult human saphenous vein ECs (AHSVECs) grown in the presence of heparin (100 micrograms/ml) and retina-derived growth factor (RDGF) studied by Northern blotting transcribed a messenger ribonucleic acid (mRNA) of 3.9 kb, strongly hybridizing to PDGF B chain probes, and two species of 2.0 and 2.6 kb hybridizing to PDGF A chain probes. Withdrawal of RDGF and heparin from these cultures for 48 hours before mRNA extraction amplified the scanning densitometric mRNA signal per cell by 8.0 +/- 7.6 fold (mean +/- SD) (N = 4 cultures) for B chain mRNA and 5.2 +/- 3.6 fold (N = 3 cultures) for A chain mRNA. In addition, AHSVEC cultures released a PDGF-like substance, because 50% vol/vol AHSVEC conditioned serum-free medium increased tritiated thymidine uptake elevenfold in PDGF receptor-bearing 3T3 cells whereas an excess (50 micrograms/ml) of nonspecific goat anti-human-PDGF antibody significantly reduced this increase by a mean of 30% to 7.0 +/- 3.4 fold (N = 6 trials, p less than 0.001). Flow cytometry determined AHSVEC cultures to be proliferating with a mean of 6.2% +/- 1.9% (N = 3 culture lines) of ECs in S phase even at confluence when deprived of EC mitogens for 48 hours. Adult human ECs, which proliferate on bypass conduits and host vessels after perioperative injury, may play a role in causing NFH by stimulating proliferation of adjacent smooth muscle cells. Prevention of NFH may require not only antiplatelet agents but also ways to prevent EC release of smooth muscle cell mitogens in response to perioperative EC injury. PMID- 3336118 TI - Differences in reendothelialization after balloon catheter removal of endothelial cells, superficial endarterectomy, and deep endarterectomy. AB - The process of reendothelialization was studied in a deendothelialized 3 cm segment of the canine descending thoracic aorta from which peripheral endothelial cell ingrowth had been prevented by impervious prosthetic graft sleeves. Three preparations were studied: (1) removal of only the endothelial cells, accomplished by flow surface drying and balloon catheter denudation, (2) removal of the superficial portion of the nonvasal media, accomplished by endarterectomy to a depth of 200 to 300 micron, and (3) removal of the entire inner (nonvasal) media, accomplished by endarterectomy to a depth of 500 to 600 micron to reach the outer (vasal) media. A total of 44 specimens were studied after implantation periods of 7, 14, 28, and 56 days. In all cases endothelial cell ingrowth from the host aorta into the test specimen was prevented by the impervious graft sleeves. In the deep endarterectomy group there were scattered areas of reendothelialization at 1 week, extensive reendothelialization at 2 weeks, almost complete reendothelialization at 4 weeks, and confluence by 8 weeks. However, in the superficial endarterectomy group scanning electron microscopy showed scattered areas of factor VIII/von Willebrand factor (FVIII/vWF)-negative, endothelial-like cells at 4 weeks, whereas at 8 weeks most of the surface was covered by endothelial cells identified by FVIII/vWF. In those specimens subjected to balloon catheter removal of endothelial cells only, reendothelialization was not seen, even at 8 weeks. PMID- 3336117 TI - Inhibition of vein graft intimal thickening by eicosapentanoic acid: reduced thromboxane production without change in lipoprotein levels or low-density lipoprotein receptor density. AB - Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density. PMID- 3336119 TI - Alterations in aortic endothelial cell morphology and cytoskeletal protein synthesis during cyclic tensional deformation. AB - Previous studies have shown that bovine aortic endothelial cells (ECs) in culture respond to repetitive tensional deformation with an increase in deoxyribonucleic acid synthesis and cell proliferation. This study was designed to determine whether cyclic tensional deformation of ECs in vitro induces different morphologic or protein synthetic responses. ECs from passages 6 through 9 were seeded in 35 mm2 well silicone rubber plates at 2 x 10(5) cells/well and allowed to attach for 24 hours. The experimental group was placed in a vacuum-operated stress-providing device that exerted an elongation of 24% at maximum downward deflection of the culture plate bottom and was subjected to repetitive cycles of 10 seconds of 24% maximum elongation and 10 seconds of relaxation for 5 days. The control group was subjected to similar incubation conditions but without stretch. 35S-methionine (500 muCi/well) was added to the plates 24 hours before harvesting, and two-dimensional gels of the harvested lysates (isoelectric focusing with pH 3 to 10 ampholytes followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis on 12.5% gels) were performed and the labeled proteins visualized by autoradiography. The data indicate that there is a differential synthesis of proteins, with synthesis of some proteins decreased or ablated whereas other proteins were increased in response to cyclic mechanical tension. The actin filament organization was evaluated after staining with rhodamine phalloidin, a fluorescent F-actin probe. The ECs subjected to tension had a more polygonal shape and demonstrated pseudopods and actin stress fibers, whereas ECs cultured under static conditions were more rounded and did not express actin stress cables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336120 TI - The effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the arterial wall. AB - The association between cigarette smoking and the development of atherosclerosis is well established, but the mechanism that makes cigarettes such a potent "risk factor" is not understood. There is normally a constant insudation of plasma macromolecules into the arterial wall. Fibrinogen and lipids are two of the large molecules involved in atherosclerosis. Therefore we studied the effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the canine arterial wall to 125I-labeled fibrinogen. The results show that inhaled cigarette smoke significantly and rapidly increases the permeability of the arterial wall to fibrinogen and that this effect can be produced with carbon monoxide alone but not with intravenous nicotine. PMID- 3336121 TI - Paraplegia after thoracic aortic occlusion: influence of cerebrospinal fluid drainage. Experimental and early clinical results. AB - Paraplegia occurs in 6.5% to 40% of patients after repair of extensive thoracoabdominal aortic aneurysms requiring aortic clamping. This study aimed to determine whether drainage of cerebrospinal fluid (CSF) done before aortic cross clamping could decrease the incidence of paraplegia in dogs. The descending thoracic aorta was clamped distal to the left subclavian artery for either 40 minutes (group I) or 60 minutes (group II). All control animals in group I (10) and group II (10) showed evidence of spinal cord injury with paraparesis or paraplegia. In contrast, 9 of 10 animals (90%) in group I and 7 of 10 animals (70%) in group II that had CSF drainage before aortic cross-clamping were neurologically normal (p less than 0.001 and p less than 0.01, respectively). Aortic pressure distal to the aortic cross clamp was the same in all groups; however, spinal cord perfusion pressure (distal aortic pressure minus CSF pressure) was significantly higher in neurologically normal animals (34 +/- 5 mm Hg, n = 15) compared with those with paraparesis (26 +/- 4 mm Hg, n = 8) or paraplegia (19 +/- 5 mm Hg, n = 8) (r = 0.871, p less than 0.001). This study demonstrates that drainage of CSF before thoracic aortic occlusion significantly increases spinal cord perfusion pressure and decreases the incidence of paraplegia. Limited early clinical experience suggests that CSF drainage may be a useful adjunct to prevent paraplegia in patients who are having repair of thoracoabdominal aortic aneurysms. PMID- 3336122 TI - Direct noninvasive monitoring of spinal cord motor function during thoracic aortic occlusion: use of motor evoked potentials. AB - Spinal cord monitoring during thoracic aneurysmectomy by somatosensory evoked potentials has been criticized for its failure to measure anterior (motor) spinal cord function. We have developed a clinically applicable, noninvasive technique for intraoperative monitoring of motor evoked potentials (MEP), which allows direct functional assessment of spinal cord motor tracts during thoracic aortic occlusion. Twelve dogs underwent continuous intraoperative monitoring of MEP before, during, and after thoracic aortic cross-clamping. Motor tract response to noninvasive cord stimulation (5 to 10 mA, 0.02 msec, 4.3 H2) was recorded by subcutaneous electrodes placed along the length of the spine (T-10, L-1, and L 4). Six animals (group I) subjected to aortic cross-clamping alone demonstrated a characteristic time- and level-dependent deterioration and loss of MEP. Ischemic cord dysfunction (as determined by time from clamping to loss of MEP) progressed from the distal to the proximal cord (L-4 = 11.3 +/- 1.5 minutes; L-1 = 14.9 +/- 2.3 minutes; T-10 = 16.9 +/- 2.3 minutes; p less than 0.05 between all levels). Reperfusion of the distal aorta 20 minutes after clamping resulted in MEP return that progressed from the proximal (T-10) to distal (L-1 and L-4) cord. In another six animals (group II), distal perfusion (mean blood pressure = 95 mm Hg) was maintained for 1 hour after cross-clamping by left atrial-femoral artery bypass. Normal configuration and amplitude of MEP was maintained throughout the cross clamping period. These data suggest that distinctive changes in MEP indicative of reversible ischemia of spinal cord motor tracts occur after aortic cross clamping. Such ischemia begins in the most distal cord, exhibits upward progression with time, and can be prevented by maintenance of adequate distal aortic perfusion. Clinical use of MEP monitoring during thoracic aneurysmectomy may provide a method for intraoperative assessment of the adequacy of motor tract perfusion. PMID- 3336123 TI - Monoclonal antibody-induced inhibition of platelet function: effects on hemostasis and vascular graft thrombosis in baboons. AB - The usefulness of antiplatelet agents in vascular graft recipients remains controversial because of uncertainties regarding drug mechanisms of action and dose-duration effects. In our study, a well-characterized murine monoclonal antibody (LJ-CP8, 10 mg/kg) was infused into baboons to assess the hemostatic consequences and antithrombotic effectiveness of blocking the platelet glycoprotein IIb-IIIa receptor for fibrinogen and other adhesive glycoproteins. Five treated animals and six control animals were evaluated with serial measurements of platelet count, bleeding time, and platelet aggregation ex vivo (in response to adenosine diphosphate and collagen). Indium 111-labeled platelet deposition onto femoral vascular grafts (4 mm inner diameter Gore-Tex) implanted immediately after antibody infusion was measured by quantitative gamma camera imaging. Although the antibody did not alter circulating platelet counts, bleeding times were immediately prolonged to more than 30 minutes (vs. 4.8 +/- 0.4 minutes pretreatment) with only partial normalization by 48 hours (8.3 +/- 1.0 minutes, p less than 0.05). Platelet aggregation in response to both collagen and adenosine diphosphate was abolished immediately and remained impaired for 48 hours. Despite the profound inhibition of platelet function, graft platelet deposition was equivalent postoperatively in both the treated and untreated groups (p greater than 0.5), averaging approximately 5 x 10(9) platelets per graft. Graft-associated indium 111-labeled platelet activity increased over 48 hours and was not reduced by the antibody treatment (p greater than 0.5 at all times). All grafts were removed at 8 days; only one graft from a treated animal was found patent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336124 TI - External carotid endarterectomy: indications, technique, and late results. AB - In the past 14 years, 22 patients (25 operated sides), with occlusion of the internal carotid artery (ICA), underwent ipsilateral external carotid artery (ECA) endarterectomy at our institution. Operative indications were amaurosis fugax in 13 sides and nonlateralizing transient ischemic attacks in the remaining 12. There were no operative deaths. One patient suffered a minor stroke after operation. Follow-up ranged from 6 to 110 months (median 36 months). In 16 cases, simple endarterectomy with or without vein patch closure was performed (type I). In two cases the ostium of the ICA was occluded with interrupted sutures after endarterectomy (type II). In the remaining seven cases the ICA was transposed as a patch over the endarterectomized ECA after endarterectomy (type III). All but six patients (six sides) underwent duplex scanning or angiography during follow up. Four of nine patients with previous nonlateralizing symptoms had persistent symptoms after operation, whereas none of those with previous amaurosis fugax did. Recurrent occlusive disease was more common in type I reconstructions (p less than 0.05). Proper ECA reconstruction results in long-term patency. In the patient with ipsilateral ICA occlusion, transposition of the ICA as a patch over the endarterectomized ECA offers a valid hemodynamic solution. Objective parameters are needed to identify patients with nonlateralizing symptoms who will benefit from operation. PMID- 3336125 TI - The comparative value of noninvasive testing for diagnosis and surveillance of deep vein thrombosis. AB - This is a prospective analysis of 351 patients in two distinct groups undergoing ascending phlebography, impedance plethysmography (IPG), and/or phleborheography (PRG) within the same 24-hour period. One hundred twenty patients also had a 125I fibrinogen uptake test (RFUT). The two patient groups consisted of the following: those patients evaluated because of suspicion of deep vein thrombosis (DVT) (diagnostic) and those patients at high risk for postoperative DVT (total joint replacement) who had routine noninvasive testing and ascending phlebography (surveillance). The overall sensitivities for IPG and PRG were significantly better in the diagnosis group (71% [69 of 97 patients] and 78% [82 of 105], respectively) compared with the surveillance group (20% [14 of 71] and 27% [17 of 63], respectively) (p less than 0.0001). The sensitivities for IPG and PRG detecting proximal (A/K) thrombi was 83% (68 of 82 patients) and 92% (79 of 86) in the diagnosis group compared with 32% (11 of 34) and 33% (9 of 27) in the surveillance group (p less than 0.0001). Although there was no difference in overall incidence of DVT between the diagnosis group (56%, 118 of 212 patients) and the surveillance group (55%, 76 of 139), the results can be explained by the difference in A/K thrombi (84% [99 of 118] and 47% [36 of 76]) (p less than 0.001) and occlusive A/K thrombi (84% [58 of 69] and 23% [7 of 31]) (p less than 0.0001), respectively. Of the patients with A/K thrombi, 97% (67 of 69) in the diagnosis group had hemodynamically detectable thrombi compared with only 48% (12 of 25) in the surveillance group (p less than 0.001). Combining the RFUT with the noninvasive studies for surveillance significantly improved the sensitivity for both A/K and distal thrombi. Patient selection also appears to have a significant influence on the results of the combination of IPG and RFUT when the current surveillance group is compared with similarly performed studies in a previously reported diagnosis group. The location and magnitude of thrombi in any patient population can be skewed depending on indications and timing of testing, thereby significantly affecting the sensitivity of noninvasive tests. IPG and PRG are reliable for evaluating patients with suspected DVT. However, patients with postoperative DVT have a high incidence of nonocclusive thrombi. Because noninvasive hemodynamic tests cannot identify accurately postoperative DVT, they cannot be used to generate epidemiologic data or as end points for studies evaluating efficacy of prophylaxis in patients undergoing total joint replacement, and anatomic studies of the deep venous system continue to be required. PMID- 3336126 TI - Detection of occult colonic ischemia during aortic procedures: use of an intraoperative photoplethysmographic technique. AB - A photoplethysmographic technique was used in 30 consecutive patients who had abdominal aortic reconstruction to assess colonic viability intraoperatively. A sterile pulse oximeter probe was used to measure arterial pulsatility and transcolonic oxygen saturation (TCOS) in the proximal, midportion, and distal sigmoid colon before and after the reconstruction. No attempt at inferior mesenteric revascularization was made, irrespective of the photoplethysmographic results. The status of the colon was assessed between the third and sixth postoperative day by a colonoscopist unaware of the intraoperative data. Before the reconstructive procedure photoplethysmography displayed pulsatile flow in all patients with a mean TCOS of 95% +/- 0.4%. After reconstruction, 28 patients (93%) demonstrated unchanged pulsatility with mean TCOS of 94% +/- 0.4%. Despite ligation of a patent inferior mesenteric artery in 10 of these patients, all 28 had normal colonoscopic examinations. By contrast, two patients (6.7%) had a loss of photoplethysmographic pulsatility with unmeasurable TCOS. Both of these patients had ligation of an initially patent inferior mesenteric artery and demonstrated evidence of ischemic mucosal changes at colonoscopy. Intraoperative colonic photoplethysmography represents an easily performed, accurate method for predicting colonic viability. A loss of pulsatility suggests inadequate postreconstructive colonic perfusion and mandates revascularization of the inferior mesenteric artery. PMID- 3336127 TI - The use of preoperative exercise testing to predict cardiac complications after arterial reconstruction. AB - To assess the value of exercise testing in the prediction of cardiac risk, 100 patients requiring arterial reconstructive surgery had either treadmill testing or arm ergometry before operation. Thirty-four patients then had abdominal aortic aneurysm repair, 48 had reconstructions for aortoiliac occlusive disease, and 18 had infrainguinal revascularization procedures. Cardiac complications included myocardial infarction in 10%, acute congestive failure in 5%, malignant ventricular arrhythmias in 7%, and cardiac death in 7%. Contingency table analysis showed that patients who achieved less than 85% of their predicted maximum heart rate (PMHR) during exercise testing had a complication rate of 24%, whereas patients who achieved more than 85% of PMHR had a 6% complication rate (p = 0.0396). The degree of ST segment depression during exercise testing was not a significant predictor of cardiac complications. However, patients who had a positive stress test (ST depression more than 1 mm) and achieved less than 85% of their PMHR had a complication rate of 33%, whereas patients with a positive stress test who achieved more than 85% of their PMHR had no complications (p = 0.048). Statistical analysis with a logistic regression model showed two factors to be significant. Patients who achieved a high maximum heart rate during exercise testing had a low probability of developing postoperative cardiac complications (p = 0.04), as did patients who achieved high cardiac work load maximal oxygen uptake (p = 0.03). We conclude that preoperative exercise testing is useful to predict cardiac complications after arterial reconstruction. Patients who are able to achieve more than 85% of their PMHR and a high maximal oxygen uptake represent a low-risk group. PMID- 3336128 TI - Neoendothelialization of small-diameter polytetrafluoroethylene arterial grafts is not delayed by aspirin and dipyridamole. AB - The effect of aspirin and dipyridamole on neoendothelialization of polytetrafluoroethylene (PTFE) was studied in the rabbit aortic graft model. Forty-three New Zealand white rabbits were allocated to receive a combination of aspirin 10 mg/kg/day and dipyridamole 10 mg/kg/day (n = 23) or placebo (n = 20). Both regimens began 3 days before insertion of PTFE aortic grafts (10 mm long and 3 mm internal diameter). Serum thromboxane B2 concentration in the control group averaged 254 +/- 22 ng/ml (+/- standard error of the mean) and 40 +/- 23 ng/ml in the treatment group (p less than 0.001). Grafts and adjacent aorta were harvested at 2 weeks (n = 4), 4 weeks (n = 9), 8 weeks (n = 13), and 12 weeks (n = 17) after implantation. Morphologic techniques, including conventional light microscopy, immunoperoxidase staining for endothelial factor VIII-related antigen, and scanning electron microscopy (SEM) demonstrated that neointima was composed of endothelial cells arising by ingrowth at anastomotic site and as islands in the center of the graft. The percentage of graft neoendothelialization was measured by SEM. At 2 weeks 18% +/- 2% of the PTFE surface was covered with endothelium in the aspirin/dipyridamole group. The percentages of graft neoendothelialization for the treatment and control groups at 4 weeks were 44% +/ 13% (n = 5) and 46% +/- 10% (n = 4) (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336129 TI - Influence of pressure, flow rate, and pulsatility on release of 6-keto-PGF1 alpha and thromboxane B2 in ex vivo-perfused canine veins. AB - The influence of pressure, flow, and pulsatility on the release of prostacyclin (measured as 6-keto-PGF1 alpha) and thromboxane (measured as TxB2) was assessed in canine jugular veins perfused ex vivo with Hanks' balanced salt solution for five consecutive 15-minute periods. Control segments were perfused at 7 mm Hg with nonpulsatile flow at a rate of 90 ml/min, whereas experimental segments were perfused with pulsatile flow as well as nonpulsatile flow at pressures of 50 or 100 mm Hg and flow rates of 60 or 130 ml/min. Prostacyclin release from control segments during the first 15-minute period was 49.5 +/- 7.4 pg/mm2/15 min, which declined to 13.9 +/- 2.5 pg/mm2/15 min after 60 minutes (p less than 0.002). Arachidonic acid stimulation during the last 15-minute perfusion period increased the release to 56.1 +/- 9.4 pg/mm2/15 min (p less than 0.002). Thromboxane release from control segments was initially 4.4 +/- 1.2 pg/mm2/15 min, which declined to 0.8 +/- 0.2 pg/mm2/15 min after 60 minutes (p less than 0.002), and subsequently increased with arachidonic acid stimulation to 1.3 +/- 0.1 pg/mm2/15 min (p less than 0.01). In contrast to control perfusion conditions, changes in nonpulsatile flow rates did not affect prostacyclin release, whereas thromboxane release was lower when perfused at 60 ml/min. Pressures of 50 and 100 mm Hg increased the initial release of prostacyclin. Similarly, pulsatile flow enhanced prostacyclin release at both low and high pressures, being more pronounced with the latter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336130 TI - AIDS commission's next report focuses on four critical issues. PMID- 3336132 TI - Leads from the MMWR. Update: Aedes albopictus infestation--United States. PMID- 3336131 TI - Radiology looks toward 21st century. PMID- 3336133 TI - Leads from the MMWR. Regional differences in postneonatal mortality--Mississippi, 1980-1983. PMID- 3336134 TI - Preventive strategies in sexually transmitted diseases. PMID- 3336136 TI - Rhymes to meet snakes by. PMID- 3336135 TI - Intentions to communicate positive HIV-antibody status to sex partners. PMID- 3336137 TI - Horseradish horrors: sushi syncope. PMID- 3336138 TI - Screening newborns for hemoglobinopathies. PMID- 3336139 TI - Training for internal medicine and emergency medicine. PMID- 3336140 TI - How common is white coat hypertension? AB - Twenty-one percent of 292 patients with untreated borderline hypertension (clinic diastolic blood pressures persistently between 90 and 104 mm Hg) were found to have normal daytime ambulatory pressures (defined from a population of normotensive subjects). These patients were defined as having "white coat" hypertension, and they were more likely to be female and younger, to weigh less, and to be more recently diagnosed than patients whose pressure was elevated both in the clinic and during ambulatory monitoring. Patients with white coat hypertension did not show a generalized increase of blood pressure lability, nor an exaggerated pressor response while at work. The phenomenon is more pronounced when blood pressure is measured by a physician than by a technician. In such patients, the pressor response may be relatively specific to the physician's office and lead to significant misclassification of hypertension. PMID- 3336141 TI - Are we training too many medical subspecialists? AB - As of 1983, 10% to 40% of cities with a population of 200,000 to 500,000 lacked a board-certified physician in one or more medical subspecialties, and many additional cities of this size had only one certified representative in many of the subspecialties. Somewhat smaller cities (population, 125,000 to 200,000) had far less complete coverage. Even when one includes board-certified internists who declared themselves subspecialists but lacked certification, there were many relatively large cities without complete coverage. Between now and 2000, an appreciable portion of the projected larger pool of board-certified subspecialists will be required to deal with a growing population and an increase in per capita demand for care. Others will locate in underserved or underserved cities, but our data suggest that even in 2000, many relatively large cities will have a deficit of most types of subspecialists. PMID- 3336142 TI - The use of Part I National Board scores in the selection of residents in ophthalmology and otolaryngology. AB - A survey of ophthalmology and otolaryngology residency program directors was conducted to determine the extent to which National Board of Medical Examiners (NBME) Part I scores are used in selection of residents in these highly competitive specialty fields. Results from 218 completed questionnaires representing nearly 90% of all US ophthalmology and otolaryngology/head and neck surgery programs were analyzed. More than three fourths indicated that Part I NBME scores were used in selecting residents; more than half of the programs used these scores as a means to determine whom to interview. The direct use of NBME scores in the residency application process is widespread; however, such use of NBME scores is not consistent with the purposes of the National Board. The preeminent role of the faculty in the evaluation of medical students and in the assessment of their clinical competence needs emphasis. PMID- 3336144 TI - Physician use of the HIV antibody test. The need for consent, counseling, confidentiality, and caution. PMID- 3336143 TI - Allergic rhinitis. PMID- 3336146 TI - Grand Rounds at the Clinical Center. PMID- 3336145 TI - Using National Board of Medical Examiners scores in selection of residents. PMID- 3336147 TI - Combating a deadly combination: intravenous drug abuse, acquired immunodeficiency syndrome. PMID- 3336148 TI - Combing diabetes' teratogenic 'suspect list'. PMID- 3336149 TI - Leads from the MMWR. Tuberculosis and acquired immunodeficiency syndrome--New York City. PMID- 3336150 TI - Leads from the MMWR. Poliomyelitis prevention: enhanced-potency inactivated poliomyelitis vaccine--supplementary statement. PMID- 3336151 TI - You don't have to be a neuroscientist to forget everything with triazolam--but it helps. PMID- 3336153 TI - Labial adhesions in sexually abused children. PMID- 3336152 TI - BCG vaccine abscesses are unrelated to HIV infection. PMID- 3336154 TI - How to avoid needle stick injury. PMID- 3336155 TI - Physician certification in alcohol and drug dependence. PMID- 3336156 TI - Lovastatin: follow-up ophthalmologic data. PMID- 3336158 TI - Listing of combined internal medicine and pediatric residencies. PMID- 3336157 TI - Sublethal exposure to microwave radar. PMID- 3336159 TI - Suicide rates for young people. PMID- 3336160 TI - Asbestos exposure-cigarette smoking interactions among shipyard workers. AB - We studied the roentgenograms, pulmonary function tests, and physical findings of 294 shipyard workers to evaluate asbestos exposure-cigarette smoking interactions. Roentgenographic parenchymal opacities, decreased pulmonary diffusing capacity for carbon monoxide, decreased flow at low lung volume, rales, and clubbing were each significantly related to the number of years elapsed since first exposure to asbestos and cigarette smoking status when analyzed by logistic regression. A dose-dependent cigarette smoking response that was consistent with synergism was present only for parenchymal opacities and decreased flow at low lung volume. These findings suggest that decreased flow at low lung volume, possibly reflecting peribronchiolar fibrosis, may be a functional corollary to smoking-associated parenchymal roentgenographic opacities among some asbestos exposed individuals. PMID- 3336161 TI - An evaluation of serum pesticide residue levels and liver function in persons exposed to dairy products contaminated with heptachlor. AB - We studied a group of 45 dairy farm family members who had consumed undiluted raw milk products known to be contaminated with residues of the pesticide heptachlor at concentrations as high as 89.2 ppm (fat basis). We compared results of serum pesticide assays for these exposed persons with results for an unexposed group of 94 persons from the same geographic area and the results from the Second National Health and Nutrition Examination Survey. The exposed group had significantly higher mean levels of primary heptachlor metabolites--ie, heptachlor epoxide (0.84 +/- 1.0 vs 0.50 +/- 0.9 parts per billion) and oxychlordane (0.71 +/- 0.8 vs 0.49 +/- 1.1 parts per billion)--than the unexposed group. In the exposed group, 21.2% had elevated serum concentrations of these same metabolites; this rate was significantly greater than the rates in both the unexposed farm family members (heptachlor epoxide, 3.8%; oxychlordane, 6.3%) and the Second National Health and Nutrition Examination Survey sample (2.5% for both metabolites). However, we found no evidence of related acute and/or subacute hepatic effects in these exposed persons regardless of their serum concentrations of pesticide residues. PMID- 3336162 TI - Development of a comprehensive supportive care team for the hopelessly ill on a university hospital medical service. AB - We developed a supportive care service for a university hospital medical service that serves a socially and medically disadvantaged urban population. The team includes a faculty physician and a clinical nurse specialist who provide primary medical care, family support, and in-service guidance to hospital staff about ethical issues. A multidisciplinary approach incorporates nursing, pastoral care, social work, and other hospital services. We report our experience from November 1985 through May 1987, during which time 222 patients were referred to the team; 212 patients were accepted. The goals and operation of the service are described. The most common (n = 62, 29%) diagnosis on referral was global central nervous system anoxia following cardiopulmonary arrest. Other severe neurological conditions accounted for an additional 79 patients (37%). Comparison of patients on the service with a similar group revealed no difference in survival rate, although hospital length of stay and charges were progressively reduced after implementation of the service. This approach to the care of hopelessly ill patients may serve as an alternative method of treatment in similar hospital settings. PMID- 3336163 TI - Competency requirements. A new approach to medical school admissions. AB - The faculty of the University of Pennsylvania School of Medicine, Philadelphia, have substituted definitions of knowledge and skills for course requirements as requirements for admission. The school expects that this action will allow students more flexibility in the development of their undergraduate academic programs, while guiding them specifically to the necessary preparation in the sciences. It is further hoped that this action will encourage the faculties of undergraduate schools to examine the way in which they prepare students for careers in medicine. This article describes the approach used for bringing about this change in policy and presents the new admissions requirements. PMID- 3336165 TI - Graduate medical education confronted. PMID- 3336164 TI - Toxic shock syndrome from Staphylococcus aureus infection at insulin pump infusion sites. Report of two cases. AB - Two young diabetic females using insulin infusion pump therapy became ill with toxic shock syndrome secondary to Staphylococcus aureus infection at the insulin infusion pump site. Physicians need to be aware of this potential complication in diabetic patients using insulin infusion pump therapy so proper management can be initiated early. Infections at insulin infusion sites are common. Patients need to be instructed in the importance of preventing infections at the pump infusion site and proper management of any abscesses that should develop. Controlled studies evaluating proper management of insulin infusion pump sites to prevent infections are needed. PMID- 3336166 TI - MCAT: desperately seeking med school. PMID- 3336167 TI - Routine prenatal screening for hepatitis B surface antigen. PMID- 3336168 TI - Leads from the MMWR. Human immunodeficiency virus infection in the United States. PMID- 3336169 TI - Leads from the MMWR. Premature mortality due to unintentional injuries--United States, 1984. PMID- 3336170 TI - Altruism, self-interest, and medical ethics. PMID- 3336171 TI - Estrogens and cardiovascular risk. PMID- 3336172 TI - Combined screening: blood pressure and cholesterol. PMID- 3336173 TI - Altered folate metabolism in early HIV infection. PMID- 3336174 TI - Was the atrial septal defect closed? PMID- 3336175 TI - Calcium antagonists and potassium balance. PMID- 3336176 TI - Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study. AB - In a 16-week randomized, double-blind, vehicle-controlled study of topical tretinoin in the treatment of photoaging, all patients applied topical tretinoin to one forearm and vehicle cream to the other. Half of the patients received tretinoin to the face, and half received vehicle cream. All 30 patients who completed the study showed statistically significant improvement in photoaging on the tretinoin-treated forearms, but not on the vehicle-treated forearms. Fourteen of the 15 patients who received tretinoin to the face had improvement in photoaging, whereas none of the vehicle-treated patients' faces improved, a statistically significant difference in response between the two groups. Statistically significant histologic changes were seen in forearm skin treated with tretinoin, but not with vehicle cream. Side effects were limited to irritation of tretinoin-exposed skin. PMID- 3336178 TI - Adult supraglottitis. A prospective analysis. AB - Epiglottitis in pediatric patients is an infection caused by Haemophilus influenzae type b, which can lead rapidly to sepsis and an asphyxial death. In an effort to study the cause and clinical course of adult epiglottitis, eight serially hospitalized adult patients with supraglottitis over a ten-month period were prospectively evaluated, including a daily laryngeal examination. Although multiple anatomic sites in the larynx and oropharynx were inflamed, the epiglottis was often not the most involved area and was actually normal in one patient. Bacterial cultures were harvested from blood, the nasopharynx, the oropharynx, and the vallecula in all patients and the preepiglottic space in two patients. In no case was H influenzae demonstrated. No patient developed respiratory compromise. It was concluded that epiglottitis is an inaccurate description of this disorder and that this non-H influenzae adult variety of supraglottitis seemingly can follow a less pernicious course than the classically described infection. PMID- 3336177 TI - Natural interferon alfa for treatment of condylomata acuminata. AB - The activity of natural (leukocyte) interferon alfa in the treatment of condylomata acuminata was assessed in a randomized, double-blind, placebo controlled, multicenter trial. Interferon alfa (Alferon N Injection) or placebo was injected into lesions twice weekly for up to eight weeks. Eighty-six patients were given interferon alfa, and 72 were given placebo. Eighty-six percent of interferon alfa-treated patients and 89% of placebo-treated patients had received previous therapy for condylomata acuminata. Side effects, usually flulike symptoms, occurred briefly after the injections; if present, they disappeared before the end of the third week of therapy. Treatment completely eliminated warts in 62% of interferon alfa-treated patients compared with only 21% of placebo-treated patients. Natural interferon alfa given intralesionally is an effective and safe treatment even in patients with recurrent or recalcitrant genital warts. PMID- 3336179 TI - Dicroceliasis (lancet fluke disease) in an HIV seropositive man. AB - Dicroceliasis is an unusual zoonotic trematode infection caused by the lancet liver fluke, Dicrocoelium dendriticum. Grazing herbivores (usually sheep or cattle) are the definitive hosts. The life cycle proceeds through two intermediate hosts: the land snail and the field ant. Human infection is acquired by consuming the field ant. This case report describes a human immunodeficiency virus-seropositive patient who presumably acquired this parasite from bottled water contaminated with ants. A brief discussion of the parasitology, pathology, clinical findings and treatment is presented. PMID- 3336180 TI - At last! A medical treatment for skin aging. PMID- 3336182 TI - Survey adds evidence that office visits indicate 'just tip of the iceberg' of medical problems. PMID- 3336183 TI - The epidemiology of missing records. PMID- 3336181 TI - Sex experts and medical scientists join forces against a common foe: AIDS. PMID- 3336184 TI - The absorbency of tampons. PMID- 3336185 TI - Tampon characteristics and menstrual toxic shock syndrome. PMID- 3336186 TI - HIV transmission, lab technicians, and open-toed shoes. PMID- 3336187 TI - A nurse-associated epidemic of cardiac arrests in an intensive care unit. AB - Review of 2219 admissions to an intensive care unit at a large urban hospital from 1983 to 1985 revealed an epidemic of cardiac arrests during the evening shift from January 1984 to March 1985. Of the 88 evening-shift cardiac arrests during this time, one specific nurse (Nurse 14) was the care giver for 57 (65%). Eight of ten epidemic-period patients who experienced shift-specific circadian recurrences of cardiac arrests were patients of Nurse 14. No therapeutic intervention and no other health care provider was as strongly associated with evening-shift cardiac arrests as was Nurse 14. Multiple logistic regression analysis demonstrated that when risk of cardiac arrest was adjusted for age, sex, severity of illness, and postoperative status, patients of Nurse 14 were 47.5 times more likely to experience arrest than were other nurses' patients. An expert determined that, compared with other nurses, the cardiac arrests among Nurse 14's patients were more likely to be consistent with unexplained hyperkalemia, to be unexpected in timing, and to be inconsistent with the clinical course. The epidemic ceased when Nurse 14 left employment at the intensive care unit in March 1985. Epidemiologic surveillance of adverse outcomes in health care settings is recommended. PMID- 3336188 TI - Hospital competition and surgical length of stay. AB - The hypothesis that competitive pressures encourage hospitals to accommodate patient and physician preferences for longer lengths of stay was tested. Seven hundred forty-seven nonfederal short-term hospitals were divided in terms of the number of neighboring hospitals within a 24-km radius, and this measure of hospital concentration and competition was measured against length of stay for ten surgical procedures, using 1982 data on 498454 patient discharges. Patient, physician, and hospital characteristics associated with length of stay were controlled for. Competition-related percentage increases in length of stay were identified for all procedures, including total hip replacement (14.8%), transurethral prostatectomy (13.9%), intestinal operations (14.0%), stomach operations (14.7%), hysterectomy (6.9%), cholecystectomy (9.1%), hernia repair (10.5%), appendectomy (8.4%), cardiac catheterization (22.9%), and coronary artery bypass graft surgery (21.2%). It was concluded that there is a strong association between the number of hospital competitors in the local market and the average length of stay in US hospitals. PMID- 3336189 TI - Effects of formaldehyde on the mucous membranes and lungs. A study of an industrial population. AB - One hundred nine workers and 254 control subjects were studied to evaluate the effects of formaldehyde on the mucous membranes and lungs. A modified, respiratory symptom questionnaire and spirometry were administered to all study participants before and after their work shift, and formaldehyde levels were determined for each test subject. Over the course of the monitored work shift, test subjects demonstrated a dose-dependent excess of irritant symptoms and a statistically significant decline in certain lung function parameters. Analysis of test and control subject data combined revealed a correlation between formaldehyde exposure and these pulmonary changes. Baseline spirometry values were not significantly different between test and control groups, and formaldehyde-exposed workers did not report an excess of respiratory symptoms. Formaldehyde is a dose-dependent irritant of the eyes and mucous membranes at low level exposures. It can exert a small, across-shift effect on airways but after a mean exposure of ten years does not appear to cause permanent respiratory impairment. PMID- 3336190 TI - The National Organ Procurement and Transplantation Network. PMID- 3336191 TI - Leads from the MMWR. Update: prevention of Haemophilus influenzae type b disease. PMID- 3336192 TI - Leads from the MMWR. Suspected nosocomial influenza cases in an intensive care unit--Georgia. PMID- 3336193 TI - AIDS, zinc deficiency, and thymic hormone failure. PMID- 3336194 TI - Babe Ruth, tobacco, alcohol, and cancer. PMID- 3336195 TI - Fake urine samples for drug analysis: hot, but not hot enough. PMID- 3336196 TI - Drug use and laboratory values in the elderly. PMID- 3336197 TI - The second Baby Doe rule. PMID- 3336198 TI - The permanent artificial heart. Four case reports. AB - This article describes the clinical course of four patients in whom the Jarvik-7 100 total artificial heart was implanted as a permanent device. Details of their preoperative assessment and comprehensive summaries of their postoperative course are presented. The neurological, hematological, renal, and infectious complications they experienced and the interventions initiated to achieve resolution of these problems are described. Finally, revisions in the treatment protocols as a consequence of the experience and knowledge gained are examined. PMID- 3336199 TI - Infectious complications in four long-term recipients of the Jarvik-7 artificial heart. AB - This article describes the infectious complications that occurred among four of the longest-term recipients of the Jarvik-7 artificial heart. Infection arising from the drive lines, with spread to the mediastinal periprosthetic space, was the major limiting factor in long-term use of the device in these patients. Periprosthetic infections were due to coagulase-negative staphylococci, Staphylococcus aureus, Pseudomonas aeruginosa, and other Pseudomonas species. Other infectious complications incurred by some of the patients included pneumonia, empyema, urinary tract infection, and intravascular line sepsis with Candida. Intensive antimicrobial therapy for prolonged periods seemed to suppress but not to eradicate infection and was accompanied by the appearance of multiresistant bacterial strains. Complications of antimicrobial therapy included diarrhea secondary to overgrowth with Clostridium difficile in two patients. Use of the current device for more than 30 days should be considered extraordinary and should be reserved for patients for whom no other form of life support is available. PMID- 3336200 TI - Biomaterial-centered sepsis and the total artificial heart. Microbial adhesion vs tissue integration. AB - The principal barrier to the extended use of the total artificial heart is infection that is centered on the biomaterial constituting the prosthetic device and exacerbated by the surrounding damaged tissue. Ultrastructural studies of total artificial hearts removed from two patients indicate a failure of true tissue integration and diffuse, adhesive bacterial colonization of biomaterial surfaces. Biomaterials are, in part, susceptible to infection because, at the present state of the art, they are usually not well integrated with host tissue or, if hemodynamic, not optimally biocompatible or antiadhesive. PMID- 3336201 TI - Clinical management of total artificial heart drive systems. PMID- 3336202 TI - Tissue specificity and species differences in the distribution of urate oxidase in peroxisomes. AB - The localization of urate oxidase in different tissues of rat and in the livers of selected mammalian species was investigated by immunoblot analysis and protein A-gold immunoelectron microscopy. Urate oxidase was purified from rat liver and used as an antigen to generate polyclonal antibodies in the rabbit. The antibodies were found to be monospecific by immunodiffusion and immunoblot analyses. By immunoblot analysis, urate oxidase was detected in the livers of rat, two strains of mice, hamster, dog, cat, and cow, but not in the Cynomolgus monkey and human liver. Urate oxidase was not detected by immunoblot method in rat kidney, jejunal mucosa, adrenal gland, testis, and pancreas. The subcellular localization of urate oxidase was ascertained by the protein A-gold immunocytochemical staining of the Lowicryl K4M embedded tissues. Urate oxidase was localized exclusively in the crystalloid core of the peroxisome in hepatic parenchymal cells of rat, mouse, hamster, dog, cat, and cow. The limiting membrane and the matrix of hepatic peroxisomes in these species were negative for the staining. The marginal plates of feline, canine, and bovine hepatic peroxisomes were also negative for urate oxidase. This enzyme was also not detected within the peroxisomes of human and monkey livers by the immunocytochemical technique. Peroxisomes (microperoxisomes) in extrahepatic rat tissues did not stain positively for urate oxidase by the protein A-gold immunocytochemical method, although they were positive for catalase. Fatty acyl CoA oxidase was present in peroxisomes of jejunal mucosa, Leydig cells of test-is and pancreas but not in adrenal gland. Administration of a hepatic peroxisome proliferator, ciprofibrate or Wy-14643, failed to induce urate oxidase in rat liver. These results indicate that urate oxidase is a liver specific protein in rat and its localization within the liver peroxisomes of six mammals, excluding man and a nonhuman primate, and that its localization is limited exclusively to the crystalloid core. Unlike fatty acyl-CoA oxidase, urate oxidase does not appear to be inducible significantly by peroxisome proliferator treatment in the rat liver. PMID- 3336204 TI - Demonstration of tumor necrosis factor in human amniotic fluids and supernatants of placental and decidual tissues. AB - Human amniotic fluid samples obtained from normal pregnancies and supernatants of normal full-term placental and decidual tissues were assayed in a specific radioimmunoassay (RIA) and in a sensitive bioassay for tumor necrosis factor (TNF). TNF was detected in 91% of amniotic fluid samples and in all placental and decidual supernatants assayed by the RIA. Amniotic fluid samples collected during the second trimester of pregnancy contained significantly higher concentrations of TNF than samples collected during the third trimester, average concentrations being 2.5 ng/ml and 0.9 ng/ml, respectively. Parallel testing in the bioassay showed that most of the amniotic fluid TNF is biologically inactive, whereas placental and decidual supernatants had biologic activity correlating with TNF levels detected by the RIA. The quantities of TNF detected by the RIA ranged from 1.1 to 2.8 ng/ml in placental supernatants and from 3.9 to 8.5 ng/ml in decidual supernatants. The presence of TNF in normal amniotic fluids and in placental and decidual supernatants suggest that this cytokine has a physiologic role in human pregnancy. PMID- 3336203 TI - Computer emulation of thin section electron microscopy predicts an envelope associated icosadeltahedral capsid for human immunodeficiency virus. AB - Electron microscopy of human immunodeficiency virus (HIV) has provided evidence for a virion model which when sectioned, consists of a circular envelope surrounding an inner conical core. When sections are perpendicular to the core axis, the envelope is still circular, but the tapered core appears as a dot near the center of the envelope. An observation inconsistent with the present model is the frequent finding of an electron-lucent "polygonal window" associated with the virion envelope. Here, we provide evidence for a new model of HIV. This model, which accounts for the polygonal windows and the shape of the envelope, places the conical core inside a regular polyhedron that lies just under the envelope. We tested the validity of various polyhedrons with three-dimensional computer graphics which emulate thin section electron microscopy. With this technique, about 2000 computer-generated "thin sections" of HIV-models were compared with electron micrographs of HIV. A structure consistent with the computer-generated data reveals a detailed model for HIV with the following features; (a) the conical core is inside an envelope-associated capsid having icosadeltahedral symmetry. This envelope-associated capsid is 60-sided and contains 32 vertices, 20 of which have hexagonal symmetry and 12 of which have pentagonal symmetry, (b) the inner rodlike core abuts the inside of any 2 opposing hexagonal vertices, (c) the pentagonal vertices do not support the inner core. A comparison of these results with that of Gelderblom et al. (Gelderblom HR, Hausmann EHS, Ozel M, Pauli G, Koch MA: Fine structure of HIV and immunolocalization of structural proteins. Virology 156: 171, 1987), suggests that the p17 polypeptide is a component of the envelope-associated icosadeltahedral capsid. This computer emulation technique provides a thorough test of this model of HIV, but does not constitute proof. Additional testing methods such as bidirectional metal shadowing and freeze etching will be needed to confirm this new virion structure. Additionally, this computer technique may be useful for testing the proposed morphology for cell organelles. PMID- 3336205 TI - Basal lamina of rat myocardium. Its fate after death of cardiac myocytes. AB - As part of a study of the interactions between myocardial cells and extracellular matrix during healing of necrotic lesions, we have examined the fate of myocyte basal lamina (BL) after injury with ischemia, freeze-thawing, or isoproterenol. Using light and electron microscopy, and antibodies to three BL-associated antigens, we found that the BL of necrotic myocytes remained largely intact and continued to delineate the myocyte compartment from connective tissue space. Inflammatory cells entered the myocyte compartment through holes in the acellular BL and removed cell debris. The holes may have been produced by inflammatory cells and/or by the stretching force of the beating heart. After removal of debris, some BL sheaths of necrotic myocytes collapsed, resulting in spatial approximation of vessels. Interstitial cells deposited collagen and elastic fibers in the connective tissue space and within portions of the myocyte compartment. The acellular myocyte BL, collapsed or not, retained normal antigen staining for type IV collagen, laminin, and heparan sulfate for about 10 days, then showed diminished staining in patchy areas. These areas may correspond to BL disruption and degradation in conjunction with fibrosis, although a substantial amount of acellular BL remained in situ and became embedded in scar tissue. At least two types of granulo-vesicular bodies, measuring 25 to 60 and 60 to 160 nm respectively, were associated with the acellular BL; these were of unknown origin and function. The study shows that the fate of acellular BL in injured myocardium is similar to the fate of BL in other injured tissues; however, the appearance of holes in acellular BL, within hours after injury, is unusual and may enhance scar tissue formation. Whether the acellular BL contributes to regeneration of myocardium, as do acellular BLs in other injured tissues, remains to be determined. PMID- 3336206 TI - In vitro spinal cord trauma. AB - Fetal mouse spinal cord explants were harvested and allowed to grow in Maximow chambers. Normal appearing matured cultures were subjected to a brief episode of impact trauma by dropping the flat surface of 25 to 105 mg dressmaker's pins from a height of 10 cm directly onto the exposed surface of the culture. Light and electron microscopic studies at selected posttrauma intervals revealed discrete foci of necrosis preceded or accompanied by nerve fiber changes (granular axoplasm, vesicular myelin, pleomorphic spheroids) identical with those documented in spinal cord trauma in vivo. Although no inherent calcification was observed, calcium was added to some of the traumatized cultures and it was subsequently localized by pyroantimonate in the axoplasm; within mitochondria, adjacent to neurofilaments, and in the cytosol. The study indicates that the morphologic sequence of events of spinal cord trauma in vitro are similar to those observed in vivo, and that the latter may occur in the absence of vascular injury. PMID- 3336208 TI - The pulmonary vascular effects of dopamine, dobutamine, and isoproterenol in unilobar pulmonary edema in dogs. AB - Although catecholamine inotropic drugs are often used to support the circulation of critically ill patients with hypoxemic respiratory failure, their effect on the pulmonary circulation and on gas exchange is incompletely understood. In order to improve our understanding of the effects of these drugs on the pulmonary circulation, we made measurements of total and regional intrapulmonary shunt (Qs/Qt), distribution of pulmonary blood flow, and pulmonary hemodynamics before and after infusions of dopamine (n = 6, 5 micrograms/kg/min), dobutamine (n = 6, 10 micrograms/kg/min), isoproterenol (n = 6, 0.1 micrograms/kg/min), or saline in dogs with unilobar oleic acid-induced pulmonary edema. In addition to permitting determination of the overall hemodynamic and gas exchange effects of these drugs, this preparation allowed measurement of changes in distribution of pulmonary blood flow between normal and edematous lung. In 6 dogs given dobutamine, mean cardiac output (CO) increased by 1 liter/min, while pulmonary arterial pressure (PPA) increased by 2 mm Hg with no change in pulmonary vascular resistance (PVR) or distribution of pulmonary blood flow. There was a 5% increase in mean Qs/Qt which, because of the lack of evidence of pulmonary vasoactivity, was attributed to time or to increased CO. Isoproterenol produced a similar increase in CO, but reduced PPA and PVR indicating pulmonary vasodilator activity. Pulmonary vasodilation was most prominent in edematous lung, resulting in an increase in relative blood flow to the edema lung lobe and a substantial increase in Qs/Qt, exceeding the increase in all other groups. Dopamine, similarly increasing CO, did not change overall PVR but reduced fractional blood flow to the edema lobe by 3.4% of CO. Neither Qs/Qt nor PaO2 changed significantly in this group. The differing effects of these agents on pulmonary hemodynamics, intrapulmonary blood flow distribution, and gas exchange have potentially significant implications affecting the choice of drug used for circulatory support in hypoxemic respiratory failure. PMID- 3336207 TI - Control of prosthetic bacterial infection: evaluation of an easily incorporated, tightly bound, silver antibiotic PTFE graft. AB - Despite the use of prophylactic antibiotics in vascular surgery, prosthetic infection rate remains 2-5%. Antibiotics bound to vascular prostheses can control experimentally induced infection but prolonged antibacterial activity has not been achieved. This study evaluates the in vivo efficacy and antibiotic retention of an easily prepared silver-antibiotic prosthesis. Prostheses were prepared by combining silver with oxacillin or amikacin using an organic solvent. After evaporation of the solvent, the graft was left impregnated with the antibiotic complex. In vivo retention studies were performed by implanting PTFE 110Ag oxacillin prostheses in four canine abdominal aortas. When prostheses were explanted at 1 week, mean antibiotic retention was found to be 20% of original activity, higher than the mean inhibitory concentration for Staphylococcus aureus. In three groups of five dogs, 20 X 7-mm prostheses of PTFE alone, PTFE silver-oxacillin, or PTFE silver-amikacin were implanted in the abdominal aorta and the grafts were inoculated with 10(7) S. aureus of a known bacteriophage type, in a closed retroperitoneal pocket. The animals were sacrificed at 1 week and the prostheses were excised for quantitative bacterial culture. PFTE silver oxacillin, and PTFE silver-amikacin prostheses had 1.7 X 10(2) and 2.0 X 10(2) colonies, respectively, significantly less (P less than 0.05) than controls (1.3 X 10(6) colonies). These data suggest that antibiotic prostheses can be easily prepared without binding agents. They retain the bound antibiotic for a prolonged period and are effective in reducing graft infection in a stringent direct contamination model. PMID- 3336209 TI - Decreased postoperative myocardial fatty acid oxidation. AB - Myocardial substrate preferences following cardioplegic arrest for coronary bypass surgery have not been established. Fatty acids are believed to be the major fuel source for aerobic metabolism. Following cardioplegic arrest arterial fatty acid levels are elevated and myocardial fatty acid accumulation without oxidation may contribute to reperfusion injury. Perioperative fatty acid metabolism was evaluated in 18 patients undergoing elective coronary bypass surgery who were randomized to receive either blood (n = 11) or crystalloid (n = 7) cardioplegia. Palmitate labeled with 14carbon was infused perioperatively and arterial and coronary sinus blood samples were obtained to calculate myocardial fatty acid extraction and oxidation before and after cardioplegic arrest. Lactate and glycerol were released from the heart during both blood and crystalloid cardioplegia, suggesting ischemic glycolysis and lipolysis. Myocardial oxygen consumption was depressed and the myocardial consumptions of lactate, glucose, and fatty acids were minimal during the first 60 min after aortic clamp removal in both groups despite high arterial concentrations. Fatty acid oxidation was minimal after blood cardioplegia and was not found after crystalloid cardioplegia. Fatty acids were extracted by the heart, but were not aerobically metabolized following cardioplegic arrest. Myocardial fatty acid accumulation without oxidation may have been deleterious. The inability of the heart to oxidize exogenous fatty acids may reflect altered myocardial exogenous substrate preferences during reperfusion following coronary bypass surgery. PMID- 3336210 TI - Effect of elective surgical procedures on tissue protein synthesis. AB - The purpose of the study was to examine whether an early decrease in protein synthesis rates occurred in any tissues after abdominal surgery in postprandial rats. Leucine-specific radioactivity in mixed protein and on tRNA was determined after continuous infusion of L-[3H]leucine. Synthesis rates of mixed protein were significantly decreased in the gastrocnemius muscle, but not in the jejunum, liver, or heart, of rats 1-2 hr after splenectomy and ovariectomy or after combining the groups that had various types of abdominal surgery. These results suggest that a very early decrease in the protein synthesis rate of the gastrocnemius muscle occurs after laparotomy. PMID- 3336211 TI - Topical beta-aminopropionitrile and biochemistry of granuloma tissue. AB - The changes of connective tissue in granuloma development were studied up to 20 days following subcutaneous implantation of polyvinyl alcohol (PVA) sponges in rats. The total protein and collagen content were found to increase from the 4th to 12th days of implantation while the content of DNA continuously decreased with the age of the granuloma. Administration of beta-aminopropionitrile (beta APN) fumarate on the intact skin overlying the implanted PVA sponge in the presence and absence of dimethyl sulfoxide (DMSO) during the growth phase of granuloma development (4th through 12th days after implantation) was accompanied by significant inhibition of collagen polymerization. This was documented by a significant increase of collagen extractable into 1 N NaCl, by a significantly reduced content of aldehydes in collagens extractable into neutral salt solution, and by a significant increase of alpha subunits and alpha/beta ratio. Topical beta APN administration had no effect on the content of DNA, noncollagenous proteins, or total hydroxyproline. We conclude that topically administered beta APN fumarate onto the intact skin penetrates the stratum corneum and effectively inhibits collagen crosslinking in the underlying granuloma tissue. The extent of the effectiveness was found to be significantly greater in the presence of DMSO. PMID- 3336212 TI - Naloxone requires circulating catecholamines to attenuate the cardiovascular suppression of endotoxic shock. AB - The opiate antagonist naloxone (NAL) improves cardiovascular performance in canine hemorrhagic and endotoxic shock. If the release of neural and adrenal catecholamines is attenuated, NAL does not produce the expected improvement in cardiovascular function in canine hemorrhagic shock. This study tests the hypothesis that an endorphin-catecholamine interaction at the heart is responsible for a part of the cardiovascular depression of endotoxic shock. Two groups of five dogs were instrumented to measure mean arterial pressure (MAP), the first derivative of left ventricular pressure over time (LV dP/dt max), cardiac output, and heart rate (HR); they were then subjected to bilateral adrenalectomy and given chlorisondamine to produce ganglionic blockade. At t = 0 min the dogs were given Escherichia coli endotoxin at 1 mg/kg (LD80). Group I animals received NAL at 2 mg/kg + 2 mg/kg.hr iv from t = 30 to t = 60. At t = 45 these animals were treated with epinephrine (EPI) at 20 micrograms/kg.hr iv until t = 60. Group II animals got EPI from t = 30 to t = 60 and NAL from t = 45 to t = 60 at the same doses as Group I. In Group I, NAL alone had no effect on MAP, LV dP/dt max, or HR. EPI significantly increased (P less than 0.002) cardiovascular parameters with MAP increasing from 52 +/- 7 to 159 +/- 14 mm Hg. In Group II, EPI produced a significant increase in all parameters, and the addition of NAL produced a further significant increase; MAP increased from 37 +/- 3 to 126 +/- 16 mm Hg with EPI and then to 175 +/- 11 mm Hg with NAL. These data support the above hypothesis and indicate that circulating catecholamines need to be present to allow naloxone to reverse the cardiovascular depression in endotoxic shock. PMID- 3336213 TI - Phase II evaluation of sequential hepatic artery infusion of 5-fluorouracil and hepatic irradiation in metastatic colorectal carcinoma. AB - Twenty-seven patients with measurable liver metastases from colorectal carcinoma were entered on a protocol of intermittent hepatic artery infusion (HAI) of 5 fluorouracil (5-FU) followed by consolidation with hepatic irradiation. Five partial responses were observed in 23 evaluable patients. Median duration of response was 3.5 months. A response was evident after chemotherapy alone in four of five responders. Hepatic irradiation converted one patient with stable disease after chemotherapy to a partial responder. Median survival for all patients was 9.0 months (range 1.5-34.0). Combined modality treatment with HAI of 5-FU followed hepatic irradiation was well tolerated but did not appear to be synergistic. PMID- 3336214 TI - Malignancy and concomitant primary hyperparathyroidism. AB - Hypercalcemia is associated with a few primary malignant neoplasms and with a variety of tumors that have spread by metastases. Hyperparathyroidism is a diagnosis that is usually not considered in these patients. At our institution, 18 patients with malignant tumors presented over a 6-year period with hypercalcemia caused by hyperparathyroidism. There were five men and 13 women with a mean age of 48 years (range 24-87 years). Primary tumors in these patients included colon carcinoma (four cases), breast carcinoma (four cases), lymphoma (four cases), thyroid carcinoma (four cases), Paget's disease (one case), and lung carcinoma (one case). Metastases of the primary tumor occurred in seven patients, and in 11 patients the tumor was not metastatic or recurrent. Serum levels of calcium, phosphate, and chloride averaged 11.8 mg/dl, and 100 mEq/liter, respectively. C-terminal parathyroid hormone (PTH) levels ranged from 300 to 1,900 pg/ml with an average of 1,150 pg/ml (normal 50-340 pg/ml). At operation, a single parathyroid adenoma was discovered in 15 patients, and four gland hyperplasia was noted in three patients. In all cases, serum levels of calcium returned to normal after operation. We conclude that patients with malignant tumors and concomitant hypercalcemia should be evaluated for the possibility of hyperparathyroidism. In cases of primary hyperparathyroidism, elevated C-terminal PTH level should be diagnostic. If hyperparathyroidism is determined to be the cause of hypercalcemia, neck exploration and parathyroidectomy are indicated. PMID- 3336216 TI - Epitheloid hemangiomatosis mistaken for carcinomatosis. AB - We present a unique case of intra and extra-peritoneal epitheloid hemangioma which was mistaken for diffused carcinomatosis, representing a clinical pathological problem, and emphasizing the unpredictable behaviour of this tumour. We are dealing with epitheloid vascular tumours, and briefly touch on the differential diagnosis, the principle of biological, pathological and clinical behaviour. Knowledge of this entity would provide an accurate diagnosis and would hence improve dealing with the problem. The conclusion is that this group of Histiocytoid-epitheloid vascular lesions have varying biological potential and this unusual functional state represents a large spectrum of cells, from normal to neoplastic endothelium. PMID- 3336215 TI - Simultaneous endometrioid carcinoma of the uterine corpus and ovary: a clinicopathologic study of 15 cases. AB - The clinical stage assigned to simultaneously presenting carcinomas of the uterine corpus and ovary remains variable, depending on which of the two sites is considered to be the primary. Simultaneous involvement may occasionally represent independent primaries, a fact often overlooked. A review of all cases with a tissue diagnosis of carcinoma involving uterus and ovary was undertaken to identify those cases which possibly represent independent primaries. Seventeen such cases were identified on the basis of pathologic features, 15 of which revealed endometrioid type carcinoma at both sites. These 15 patients, who constitute the study group, were treated surgically with or without adjuvant therapy. Thirteen patients have been followed up for 1 to 12 years. Twelve patients are alive and free of disease. Vaginal vault recurrence occurred in a single patient. This was treated successfully. One patient died of an unrelated cause. The good survival fortifies the pathological impression that these cases represent independent primaries. PMID- 3336217 TI - Surgical considerations in maxillofacial prosthetic rehabilitation of the maxillectomy patient. AB - The radical maxillectomy performed for cancer of the paranasal sinuses has as its sequella some of the potentially most devastating functional losses in the field of head and neck oncology. The patient is left after surgical management with a defect that often prevents effective speech, deglutition, and mastication. This paper addresses the surgical considerations involved in the performance of a radical maxillectomy that can result in a favorable defect allowing subsequent optimal prosthetic rehabilitation of the patient. PMID- 3336218 TI - Adenomatoid tumors in the tunica albuginea of the testis. AB - Adenomatoid tumors of the tunica albuginea of the testis is rarely seen. Only 15 such cases have been described. A patient is presented in whom such a tumor was found and excised through a scrotal incision. He is alive and well 27 years later. The author presents reasons for the type of scrotal exploration done. The pathological histology is discussed. An adenomatoid tumor can easily be confused with a prostatic adenocarcinoma on frozen section. PMID- 3336219 TI - Radiation therapy for squamous cell carcinoma of the esophagus. AB - Between 1965 and 1981, 119 patients with squamous cell carcinoma of the esophagus were treated with radiation therapy with curative intent. Radiation was employed in combination with surgery and delivered pre- and/or postoperatively in 20 patients (17%). The remainder received radiotherapy alone. The overall survival rate was statistically higher in patients who had surgery and radiation compared to the group receiving radiation alone. The one-, two-, and five-year survival rates of patients receiving combined treatment vs radiotherapy alone were 65% vs 35%, 25% vs 14%, and 15% vs 6%. Age, total radiation dose, and inclusion of the supraclavicular areas in the radiation portals did not impact on outcome. Other prognostic factors are discussed. Long term survivors were noted to be at substantial risk for the development of a second epidermoid malignancy in the upper aerodigestive tract. Cumulative risk at five years was approximately 25%. PMID- 3336220 TI - The rabbit as an experimental animal for tracheal surgery. AB - The circumferential resection of the trachea with end-to-end anastomosis is a well-established clinical procedure. Still, some problems remain to be solved, such as the choice of optimal suture material. Dogs are primarily used for experimental work in this field, but are difficult to obtain. This operation was performed on nine rabbits, eight of whom survived to the preplanned date of sacrifice. Two of the survivors were found to have severe stricture at the anastomosis. This study indicates that the rabbit is a suitable experimental animal for circumferential resection and anastomosis of the trachea. PMID- 3336221 TI - Inhibition of macrophage- and neutrophil-mediated cytotoxicity by verapamil. AB - Peripheral blood monocyte-derived macrophages and polymorphonuclear leukocytes (PMNs) obtained from normal donors kill tumor cells in vitro. However, if verapamil is added to the macrophages or neutrophil tumor cell suspensions in microgram concentrations (0.1 microgram to 0.1 mg), there is marked inhibition of tumor cell killing. The inhibitory effect for the macrophages resulted from an effect of verapamil on both the effector and target cells. When either the effector cells or target cells were preincubated with verapamil, they became resistant to the effects of the cytotoxic macrophages. Cytotoxicity was also inhibited when 0.1 mg of verapamil was added to the macrophages monolayers either at the time of addition of the tumor cells or 15-30 min after addition of the tumor cells, whereas no inhibition of cytotoxicity occurred when verapamil was added more than 30 min after the initiation of the cytotoxic reaction. For the neutrophils it was observed that the inhibitory activity resulted from an effect of verapamil on the effector cells rather than the target cells. When the effector cells were preincubated with verapamil they became incapable of killing the tumor cells, whereas preincubation of the target cells with verapamil had no effect on their ability to be killed by the neutrophils. Cytotoxicity was also inhibited when 0.1 mg of verapamil was added to the neutrophil monolayers either at the time of addition of the tumor cells or 15-60 min after addition of the tumor cells, whereas no inhibition of cytotoxicity occurred when verapamil was added more than 60 min after the initiation of the cytotoxic reaction. PMID- 3336222 TI - Parotid lymph node metastases from squamous cell carcinoma of the skin. AB - Nineteen parotid lymph node metastases from squamous cell carcinoma of the skin were treated, seven with irradiation and 12 with surgery and postoperative irradiation. In the group treated with combined therapy, size of nodal metastasis and extent were strong predictors of relapse. Further postoperative irradiation with 60 Gy is not adequate to control extensive parotid nodal disease. Finally, elective treatment of clinically negative parotid nodes is not necessary in patients who can be closely followed, since early nodal disease can be controlled readily. PMID- 3336223 TI - Improved myocardial protection by oxygenation of St. Thomas' Hospital cardioplegic solutions. Studies in the rat. AB - The effect of oxygenation (100% oxygen) of the St. Thomas' Hospital cardioplegic solutions No. 1 (MacCarthy) and No.2 (Plegisol, Abbott Laboratories, North Chicago, Ill.) was examined in the isolated working rat heart subjected to long periods (3 hours for studies with solution No. 1 and 4 hours for studies with solution No. 2) of hypothermic (20 degrees C) ischemic arrest with multidose (every 30 minutes) cardioplegic infusion. At the aortic infusion point the oxygen tension of the oxygenated solutions (measured at 20 degrees C) was in the range of 320 to 560 mm Hg whereas that of the nonoxygenated solutions was less than 150 mm Hg. Twenty hearts (10 oxygenated and 10 nonoxygenated) were studied for each solution. The studies with solution No. 1 demonstrated that oxygenation led to a significant (p less than 0.05) reduction in the incidence of persistent ventricular fibrillation during postischemic reperfusion. Oxygenation of the cardioplegic solution also improved postischemic functional recovery so that the recovery of aortic flow was improved from 18.7% +/- 8.9% (of its preischemic control level) in the nonoxygenated group to 54.6% +/- 6.6% in the oxygenated group (p less than 0.025). Creatine kinase leakage was also significantly reduced from 27.5 +/- 4.8 to 9.9 +/- 0.6 IU/15 min/gm dry weight (p less than 0.005). Studies with solution No. 2 indicated that protection was better than with solution No. 1, even in the absence of oxygenation. A better degree of functional recovery was obtained after 4 hours of arrest with solution No. 2 than that obtained after only 3 hours of arrest with solution No. 1, and persistent ventricular ventricular fibrillation was never observed with solution No. 2. However, despite the superior performance with solution No. 2, further improvements could be obtained by oxygenation, with that time from the onset of reperfusion to the return of regular sinus rhythm being reduced from 55 +/- 8 to 35 +/- 2 seconds (p less than 0.01), postischemic recovery of aortic flow increasing from 59.8% +/- 7.4% to 85.7% +/- 2.5% (p less than 0.005), and creatine kinase leakage being reduced from 38.1 +/- 7.3 to 16.2 +/- 1.5 IU/15 min/gm dry weight (p less than 0.005). It is concluded that oxygenation of the St. Thomas' Hospital cardioplegic solutions improves their ability to protect the heart against long periods of ischemia and that this is manifested by improved postischemic electrical stability, functional recovery, and reduced creatine kinase leakage. PMID- 3336224 TI - Treatment of extensive aortic aneurysms by a new multiple-stage approach. AB - A new multiple-stage approach to extensive aneurysmal disease of the aorta is presented. The method is designed to obviate the proximal graft-to-aorta anastomosis in second-stage and third-stage aortic replacement to simplify and facilitate these operative steps. Since 1981 a total of 17 such procedures were performed in seven patients with dissecting and nondissecting aneurysms without deaths or complications related to the method. PMID- 3336225 TI - Resection of more than 10 lung segments. A 30-year survey of 30 bronchiectatic patients. AB - A series of 30 bronchiectatic patients, treated by bilateral resection of 11, 12, or 13 lung segments, has been followed up for 30 years. The progress of the patients is analyzed and the results of treatment are evaluated. Ten patients required further resections for persisting collapse, kinking of the apical segment of a lower lobe, or because the previous resection had been too limited. The long-term results of these extensive bilateral resections in our group of patients are excellent. The quantitative function, more than 20 years after the last resection, lies markedly above the predicted value for the number of remaining segments. The qualitative function did not deteriorate over the years. It is clear that extensive bilateral bronchiectasis does not, per se, constitute a contraindication to resection, provided that at least six normal segments can be preserved. PMID- 3336226 TI - Cerebral autoregulation during deep hypothermic nonpulsatile cardiopulmonary bypass with selective cerebral perfusion in dogs. AB - We evaluated effects of hypothermic cardiopulmonary bypass on the cerebral circulation and metabolism of six dogs over a temperature range of 37 degrees to 20 degrees C under alphastat acid-base regulation (uncorrected for body temperature). Cerebral metabolic rate for oxygen was determined from the difference between arterial and sagittal sinus blood oxygen contents, and direct cerebral blood flow measurements of the venous outflow from the isolated sagittal sinus. After core cooling at a constant perfusion flow rate of 80 ml/kg/min, cerebral blood flow significantly reduced to 10.0 +/- 1.1 ml/100 gm/min at 20 degrees C (20% +/- 2% of that at 37 degrees C) because of an increase in the cerebral vascular resistance (339% +/- 48%). Cerebral metabolic rate for oxygen reduced to 18% +/- 2%. The upper body vascular resistance decreased to a greater extent than the lower body resistance (37% +/- 4% versus 82% +/- 12%). In the selective cerebral perfusion system at 20 degrees C, when perfusion pressure (mean carotid arterial pressure minus central venous pressure) was lowered from 90 mm Hg by graded reduction of the perfusion flow rate, cerebral blood flow remained constant down to a perfusion pressure of 40 mm Hg, then steeply declined. Cerebral metabolic rate for oxygen also kept a constant level down to 30 mm Hg, then fell abruptly. Definite autoregulatory response was detected even in profound hypothermic nonpulsatile cardiopulmonary bypass. These results suggest that cerebral perfusion flow should be regulated so as to keep the perfusion pressure within the range of cerebral autoregulation to prevent cerebral ischemia or hyperperfusion, especially during selective cerebral perfusion for operations on the aortic arch. PMID- 3336227 TI - A new method for separate lung ventilation. AB - Separate lung ventilation is obtained with selective intubation of the main bronchus by an appropriate cuffed tube inserted through a standard orotracheal tube. Ventilation is carried out separately through the bronchial tube on one side and the residual tracheal tube lumen on the other side. This method, used in 144 patients, greatly simplifies the technique of bronchial intubation and offers many advantages over commercially available double-lumen tubes. PMID- 3336228 TI - Aortic arch thrombosis in the neonate. AB - Thrombotic occlusion of the aortic arch in the neonate is a rare lesion for which successful operative repair with survival beyond the immediate postoperative period has not been previously reported. We report a case in which surgical repair of this lesion with survival was achieved and discuss the diagnostic and technical aspects of management of aortic arch thrombosis in the neonate. PMID- 3336229 TI - The early results of treatment of simple transposition in the current era. AB - A total of 187 neonates with simple transposition of the great arteries (TGA) have been entered into a twenty institution cooperative study between Jan. 1, 1985, and June 1, 1986. Eighty-two percent entered within the first 2 days of life. Seventy-six of the 187 patients were initially entered into a treatment protocol leading to an arterial switch repair, 45 into one leading to an atrial switch (Mustard) repair, and 49 into one leading to a Senning repair. Five (7%) of the patients entered initially into an arterial switch protocol later were crossed over to an atrial switch protocol, and 7% of those entered into an atrial switch (Mustard) protocol were crossed over to an arterial switch protocol. Formal follow-up information is available on all patients. Only 5% of patients entered into an arterial switch protocol were without repair 2 weeks after entry, whereas 96% and 100%, respectively, of those entered into a Mustard or Senning atrial switch protocol were without repair at that time. Ninety-seven percent of the first group had no preliminary procedures other than balloon atrial septostomy, which was true of only 76% and 90%, respectively, of the last two groups. No deaths before repair occurred in the first group, whereas five occurred in the latter two groups (P = 0.06). Overall survival rate among the 187 patients was 81% at 1 year. The only risk factors for death were birth weight, date of entry into the study, and an arterial switch protocol in the group of institutions at high risk for arterial switch repair; neither an arterial nor an atrial switch protocol was a risk factor per se. According to the multivariate equation, the 12-month predicted survival rate of a patient with a birth weight of 3.4 kg, entered currently into atrial or arterial switch protocols (except in the high risk for arterial switch group of institutions) is 92%. PMID- 3336230 TI - Retrograde dissection of the left main coronary artery after endarterectomy: a rare complication. AB - The case of a 72-year-old woman who died after bypass grafting and endarterectomy of the left anterior descending coronary artery is described. At autopsy a large intramural dissection of the left anterior descending artery that extended proximally to the left main ostium from the endarterectomy site was found. The dissection was associated with clotting of the false lumen and of the graft, and with a myocardial infarct that precipitated this woman's intraoperative death. PMID- 3336231 TI - Scooping of the ventricular septum in atrioventricular septal defect. PMID- 3336232 TI - Aspirin anticoagulation for mechanical heart valves and Reye's syndrome. PMID- 3336233 TI - Arterial switch in simple and complex transposition of the great arteries. AB - Arterial switch for repair of transposition of the great arteries was performed on 53 patients since October 1983. These patients were divided into three groups: group I, 25 infants with an intact ventricular septum who had primary repair in the first month of life (2 to 34 days of age, mean 9.7 +/- 6.6); group II, 13 patients with an intact ventricular septum who had anatomic repair after a preliminary procedure (pulmonary artery banding in 13, shunt in 10, atrial septectomy in 1); and group III, 15 infants with transposition of the great arteries and ventricular septal defect. In group III, six patients had Taussig Bing abnormality, nine had previous pulmonary artery banding, three had coarctation of the aorta repaired earlier in life, and four were less than 2 weeks old. Overall early mortality was 9.4% (5/53: group I 8%, group II 7.6%, group III 13.3%). Two late deaths occurred in group II 10 and 12 weeks postoperatively after infection and high fever. A third late death 18 weeks postoperatively was due to aspiration in an infant with Goldenhar's syndrome. Mortality and morbidity decreased significantly after an initial learning period (no deaths from July 1985 to March 1987 overall, and none in the last 15 infants operated on in group I). The surviving 45 patients are doing well. All have normal sinus rhythm. Two had transient asymptomatic arrhythmias. Left and right ventricular function assessed by echocardiogram and postoperative cardiac catheterization were within normal ranges in all but two patients, one with pulmonary artery stenosis and one (Taussig-Bing abnormality with two large ventricular septal defects) with severe pulmonary vascular disease (9.6 units) observed before anatomic repair. The right ventricular pressure at catheterization ranged from 27 to 42 mm Hg in 12 patients and was 55 mm Hg in two. There was no aortic stenosis. Aortic insufficiency was trivial in three patients and mild in one. We conclude that excellent results can be obtained with arterial switch for transposition of the great arteries with or without ventricular septal defect, especially in neonates. PMID- 3336234 TI - Reconstruction of stenotic or nonconfluent pulmonary arteries simultaneously with a Blalock-Taussig shunt. AB - Stenosis or discontinuity of the pulmonary arteries associated with congenital cardiac defects was repaired in 12 patients, in conjunction with the Blalock Taussig shunt. This approach was based on the following concepts: (1) The shunted blood is more uniformly distributed to both lungs, which avoids predominance of flow to the ipsilateral lung and long-term pulmonary vascular damage; (2) because adequate blood flow is maintained, the contralateral lung growth will be near normal; (3) the possibility of future surgical correction is enhanced. The ages of the patients ranged from 2 to 24 months. Five had a primary diagnosis of tetralogy of Fallot, three had double outlet of the right ventricle, three had single ventricle, and one had a truncus type anomaly. All operations were performed without cardiopulmonary bypass. Dilation of the stenotic segment was performed in two patients, enlargement of the stenotic segment in three, and resection of the segment and end-to-end anastomosis in four. Nonconfluent pulmonary arteries were corrected in three patients. In one, the stenotic segment was resected and an anastomosis was made between the left pulmonary artery and pulmonary trunk. In another patient, a segment of the right subclavian artery was interposed between the pulmonary trunk and intrahilar left pulmonary artery. In the third patient, the right pulmonary artery was disconnected from the aorta and a tube was interposed between the right and left pulmonary arteries. There were no intraoperative or late deaths, and postoperative angiographic evaluations were satisfactory. We believe that in infants needing a Blalock-Taussig shunt the pulmonary artery anomalies, if present, should be corrected simultaneously. PMID- 3336235 TI - Anatomic repair of anomalies of ventriculoarterial connection associated with ventricular septal defect. I. Criteria of surgical decision. AB - The feasibility of anatomic repair (defined as the reconstruction of normal ventriculoarterial connection) was investigated in 104 patients who underwent an operation for anomalies of ventriculoarterial connection associated with ventricular septal defect. Three types of anatomic repair were used: intraventricular rerouting, REV (association of intraventricular rerouting with translocation of the pulmonary arterial trunk on the right ventricle), and arterial switch associated with closure of the ventricular septal defect. Intraventricular repair was considered to be the best and simplest method when possible. In the other cases, REV was indicated if pulmonary outflow tract obstruction was present, and arterial switch was performed when the tract was patent. The feasibility of intraventricular repair was related to the distances between the tricuspid valve and the semilunar valves. Preoperative measurement of these distances is an essential criterion to choose the appropriate repair of anomalies of ventriculoarterial connection associated with ventricular septal defect. PMID- 3336236 TI - Anatomic repair of anomalies of ventriculoarterial connection associated with ventricular septal defect. II. Clinical results in 50 patients with pulmonary outflow tract obstruction. AB - From November 1980 to November 1985, 50 patients underwent anatomic repair of anomalies of ventriculoarterial connection associated with ventricular septal defect and pulmonary outflow tract obstruction. The technique used was one that we have previously described, which we call REV. The principles of this technique are resection of the infundibular septum, construction of a tunnel connecting the left ventricle to the aorta, and direct anastomosis, without a prosthetic conduit, of the pulmonary arterial trunk with the right ventricle. The tunnel is situated beneath the aortic valve and occupies very little space in the right ventricular cavity. Age at operation ranged from 4 months to 13 years (mean 3.5 years). Twenty-six patients had a classic type of transposition of the great arteries; all other patients had various types of anomalies of ventriculoarterial connection in which it was impossible, after the intraventricular connection of the left ventricle to the aorta, to use the natural pulmonary orifice for the pulmonary outflow tract reconstruction. There were nine hospital deaths (18%) and one late death. Twenty-six of 29 patients whose follow-up time exceeded 1 year had an excellent clinical result. No stenosis of the aortic outflow tract was found. Four patients had significant pressure gradients on the pulmonary outflow tract. Our present experience with REV suggests that this technique allows anatomic repair in a wide variety of anomalies of ventriculoarterial connection associated with ventricular septal defect and pulmonary outflow tract obstruction, even in infants, with an acceptable rate of mortality and morbidity. PMID- 3336237 TI - Neoadjuvant chemotherapy for locally advanced transitional cell carcinoma of the bladder: do local findings suggest a potential for salvage of the bladder? AB - Sixteen patients with locally advanced transitional cell carcinoma of the bladder were given two to four cycles of combination chemotherapy with methotrexate, vinblastine, doxorubicin hydrochloride (Adriamycin), and cisplatin (M-VAC) in an effort to reduce tumor size and enhance the potential for surgical resection. All patients had initial clinical staging (based on cystoscopy and cystoscopic biopsy, urine cytology, computed tomographic scanning, and excretory urography). Before each cycle, all patients had repeat clinical staging tests. Ten patients underwent postchemotherapy bilateral pelvic lymphadenectomy and radical cystoprostatectomy, and their bladders were examined histopathologically by step sectioning techniques. One patient underwent abdominal exploration, bilateral pelvic lymphadenectomy, and ipsilateral partial cystectomy. Five patients had repeat clinical staging only without removal of their bladders. Of the 16 patients, 5 (31%) had residual invasive tumor and no tumor response. Three patients (19%) had a partial response, two of whom had only carcinoma in situ (one with prostatic duct involvement) and one of whom had stage pT1, NO, MO disease. Five patients (31%) had normal findings on computed tomographic scans, cystoscopy, biopsy, and urine cytology and thus had complete responses. In addition, 3 of 11 patients who underwent pathologic staging had no residual tumor on clinical and surgical staging and were complete responders. The overall (partial + complete) response rate was 69%, and the overall complete remission rate (pathologic + clinical staging) was 50%. These results suggest that the concept of possible salvage of the bladder with the current treatment program might be premature and must be applied selectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336238 TI - Anorexia nervosa: an immunohistochemical study of the pituitary gland. AB - The morphologic features of the anterior pituitary gland were studied by immunohistologic methods in 12 patients who had died of complications of anorexia nervosa, 4 patients who had died while on a "crash diet", 13 patients who had died of organic disease associated with inanition, and 5 age- and sex-matched control subjects who had been involved in sudden fatal accidents. All known pituitary hormones were found to be present. Abnormalities noted in both the patients with anorexia and those with organic inanition included relative hypogranulation of adrenocorticotropic and, to a lesser extent, growth hormone cells. These changes are of unknown importance but are likely the result of starvation in that they were not observed in patients on a "crash diet" or in control patients. We conclude that no specific or etiologic abnormalities are present in the pituitary glands of subjects with anorexia nervosa and that the altered secretion of adenohypophyseal hormones often noted in patients with this disorder cannot be attributed to a primary pituitary disorder. PMID- 3336240 TI - Eosinophilia associated with perimyositis and pneumonitis. AB - We describe a patient who had severe myalgias, bronchial asthma, pulmonary infiltrates, and eosinophilia. The findings on physical examination and the erythrocyte sedimentation rate were normal; there was no elevation of the serum creatine kinase. Muscle biopsy demonstrated an inflammatory exudate that contained eosinophils, localized primarily to the perimysium. Pulmonary and muscle manifestations responded to corticosteroids. Systemic eosinophilic disease associated with perimyositis or myositis has not been reported previously. In addition, we review the spectrum of eosinophilic muscle diseases--eosinophilic perimyositis, eosinophilic polymyositis, and focal eosinophilic myositis. PMID- 3336239 TI - Platelet-inhibitor treatment of diabetic nephropathy: a 10-year prospective study. AB - We prospectively evaluated a platelet-inhibitor regimen of dipyridamole and aspirin in 28 patients with insulin-dependent diabetes mellitus and well established nephropathy. After a mean treatment period of 4.3 years, iothalamate clearance (Ciot) was reasonably well maintained and urinary protein excretion was reduced in 7 patients (25%), whereas 21 (75%) had progressive nephropathy. Analysis of outcome revealed that all 7 patients with stable nephropathy and 9 of the 21 with progressive disease had baseline Ciot values that exceeded 50 ml/min per 1.73 m2. Shortened platelet survival improved after 3 months of treatment, and the distribution between patients who had stable and those who had progressive disease was approximately equal. Mean changes in fasting plasma glucose level, glycosylated hemoglobin, and blood pressure did not differ between these two groups. In a short-term protocol, urinary protein and thromboxane B2 significantly declined, whereas variable urinary levels of prostaglandin E2, 6 ketoprostaglandin F1 alpha, and Ciot did not change after 3 months of treatment with dipyridamole and aspirin. These findings suggest that treatment with dipyridamole and aspirin may stabilize renal function by reducing platelet hypersensitivity and production of thromboxanes by platelet or renal tissue (or both). In turn, constrictor activity in the glomerular vessels, mesangial contractility, and glomerular membrane permeability are decreased. These data also add evidence in support of a role for thromboxane A2 in the pathogenesis of experimental and human glomerular disease. PMID- 3336241 TI - National Cholesterol Education Program: does the emperor have any clothes? PMID- 3336242 TI - Changes in ambulatory testing for hypertensive patients 1971-1980. AB - To determine temporal changes in the outpatient use of diagnostic tests, the authors studied ambulatory testing for 208 patients diagnosed with uncomplicated hypertension, cared for by 15 private office internists in 1971 through 1980. Patients diagnosed and treated earlier in the decade tended to have significantly higher blood pressure. After adjustment for blood pressure, use of diagnostic tests in terms of total charges for testing per patient per year peaked between 1973-74 and thereafter remained fairly stable at a level slightly lower than that in 1973-74. Considering the decade as a whole, use of tests was generally greater for patients with higher blood pressure readings (P less than 0.05). These findings suggest that use of tests for hypertensive patients in outpatient settings is related to severity of disease. Although treatment of new patient groups may be one factor increasing medical costs, the use of tests per se may have stabilized for diseases in which the diagnostic technologies have remained stable. PMID- 3336244 TI - Some methods for measuring the geographic accessibility of medical services in rural regions. AB - This paper presents two complementary measures of geographic access to medical care in rural regions that necessitate only modest information inputs on the location of services and client populations. An application for the Abitibi Temiscamingue region in the Province of Quebec, Canada, is used to illustrate the types of product yielded by the measures. These include mapped patterns of potential accessibility by rural community and a graphic display of the delivery system's potential effectiveness in 'reaching' distant consumers. The relevance of the measures to the planning of medical care provision in rural areas is discussed, as is their extension through disaggregation and improvement of data inputs. PMID- 3336243 TI - A comparison of data from dental charts, client interview, and client mail survey. AB - Dental records and client survey reports were compared as sources of data for dental research. Further, two forms of the client survey were completed, a mail survey and telephone interview. A random sample of 271 clients of a dental group practice based within a university health service was selected. The Kappa values indicated a reasonable level of agreement of client survey and dental record with regard to the types of services received but no with regard to actual number of visits. Responses to the mail and the telephone versions of the client survey were compared for service satisfaction, hygiene behavior, and attitude and belief variables. Two potential sources of bias: nonrespondent/respondent bias and other response biases, such as acquiescent responses, were detected. The study illustrates the importance of weighing which source of response bias is more crucial to the general validity of a study based on the research questions to be addressed. PMID- 3336245 TI - Effectiveness of smoking cessation interventions integrated into primary care practice. AB - Using a complete factorial design, we tested three interventions for smoking cessation in routine primary care practice. The interventions tested were 1) physician counseling, 2) mailed letters and educational materials designed by the National Cancer Institute (NCI), and 3) referral to smoking cessation classes. Thirty-seven family practice physicians at three of Group Health's outpatient facilities participated. Patient participation rates were 95%, and follow-up was complete for 92% of those participating. None of the interventions had any effect on point prevalence of quitting as determined 8-9 months later by self-report. However, the combination of physician counseling and NCI materials doubled the odds of occurrence of significant antismoking behavior (quit, quit and relapse, or cut down) during the ensuing 8-9 months in those individuals receiving that combination. Referral to smoking cessation classes was strikingly ineffective in this setting. Of 369 individuals designated by study design for referral, only 14% even investigated the classes. This compares with a 10% self-referral rate for those persons not designated for referral by our study design. Our results and other recent work suggest that more intensive interventions on multiple occasions based on relapse prevention strategies hold promise for future success in smoking cessation efforts in primary care. PMID- 3336247 TI - Risk preference and admitting rates of emergency room physicians. PMID- 3336246 TI - Prospective reimbursement and diabetes mellitus. Impact upon glycemic control and utilization of health services. PMID- 3336248 TI - The effect of computerized feedback coupled with a newsletter upon outpatient prescribing charges. A randomized controlled trial. PMID- 3336249 TI - Factors affecting the utilization of specialty and general medical mental health services. AB - This study compares the extent to which need, predisposing, and enabling factors affect the use of mental health services in the specialty and general medical health sectors during a 6-month period. Data are drawn from the first wave of interviews of the Epidemiological Catchment Area (ECA) project at the Yale University site. The results indicate that 1) in the general population, factors affecting use of the two sectors differ; 2) among those using any mental health services, factors affecting use of the two sectors differ; 3) indicators of need have the strongest relationships with utilization; and 4) the effects of predisposing and enabling factors are contingent upon the presence of need. PMID- 3336250 TI - Effects of photosensitizer (hematoporphyrin derivative-HPD) and light dose on vascular targets in the albino mouse ear. AB - Photodynamic damage to normal tissues, including skin, appears to occur by photooxidative damage to the normal microvasculature as the primary target sensitized by HPD bound to the vascular wall or endothelial cell. Initial damage to the microvasculature was measured by the increase in vascular permeability (VP) as measured by Evans Blue dye (EB) extravasation as a function of HPD and laser light (632 nm) dose. Albino, Swiss-Webster mice (female 122-25 g, 5 mice per group) were injected intraperitoneally (IP) with incremental doses of HPD (Photofrin II, Photofrin Medical, Inc.) (1, 10, 20, 30, 40 and 50 mg/kg). After 48 hours the left ear of each mouse was masked as a control and the right ear was irradiated at 632 nm using the Aurora-Lexel Argon-dye laser (Cooper Laser Sonics, Inc.) with an intensity of 50 mW/cm2 and light doses of 0, 25, 50, 75, and 100 J/cm2 directed to a 3-mm spot on the mouse ear. No EB leakage occurred in the absence of HPD at any light dose or in the absence of light at any HPC dose. Vascular permeability increased as a function of HPD dose up to 30 mg/kg. AT 50 mg/kg HPD, there was a decrease in VP. At each HPD dose above 10 mg/kg, the VP increased as a function of light dose up to 75 J/cm2. Further increase in light dose was without effect. The amount of HPD porphyrin recovered from irradiated ears decreased as a function of light dose. There appeared to be an irreversible photo destruction of the porphyrin exposed to light. PMID- 3336252 TI - Stabilizing the lateral crural flap in septorhinoplasty. PMID- 3336251 TI - Biostimulation of human carcinoma cells with the argon laser: a previously unreported potential iatrogenic effect of lasers. AB - The human squamous carcinoma cell line P3 was subjected to treatment with a single mode argon laser at 514.5 nm. The temperature and energy levels delivered to the target cells were determined by a reproducible method of dosimetry. At energy levels between 860 to 990 J/cm2 and a corresponding temperature of 39 +/- 1 degrees C, a significant delayed stimulation in DNA synthesis was noted after 24 hours, but the cells remained viable. However, at energy levels and temperatures higher or equal to 1100 J/cm2 (41 degrees C), an immediate suppression of DNA synthesis was accompanied by nonviability of the P3 carcinoma cells. These results indicate that the argon laser has potential for selective biostimulation on carcinoma cell duplication at the specific "non-thermal" range of 39 +/- 1 degrees C. Similar effects were not observed when the P3 carcinoma cells were heated to this same temperature using a standard heat bath. This phenomenon appears to represent a previously undescribed potential iatrogenic effect of the monochromatic laser beam in the treatment of cancer. PMID- 3336253 TI - Acoustic otoscope for detecting middle-ear effusion. PMID- 3336254 TI - The surgical management of epidural mucoceles. AB - Mucoceles of the paranasal sinuses extending into the epidural space are both uncommon and difficult to surgically manage. To best overcome the problem of recurrent disease, we have adopted a combined otorhinolaryngologic-neurosurgical approach which emphasizes removal of as much as possible of the mucocele and marsupialization, or permanent drainage, of the disease site into the nasal cavity. Recently, we have modified this procedure in selected cases to include resection of involved dura and isolation of the epidural space from the nasal cavity. The indications and results of both forms of management are now reported in ten patients. PMID- 3336255 TI - Frontal sinus fractures: some problems and some solutions. AB - Head trauma can result in serious injuries leading to life-threatening situations. Often accompanying these injuries are fractures involving the frontal sinus. Some fractures are subtle and difficult to diagnose, while others are massive and difficult to treat. The experience at this institution in the management of frontal sinus fractures is examined. Particular emphasis is placed on the problematic cases. These include fractures that were nearly overlooked, those that were associated with massive CSF leaks, and those which were extensively comminuted. In treating some of the most severe compound injuries, a frontalis myofascial flap has been used successfully to "plug" the site of CSF leakage. The review will include the types of fractures encountered, associated injuries, errors in diagnosis, the treatment rendered, and the complications which resulted. As encountered in other studies relating to trauma, adequate follow-up has been a serious shortcoming. The protocol presently used in the management of these injuries will be outlined. PMID- 3336256 TI - The effects of anesthesia on middle-ear effusions. AB - Surgeons occasionally note a discrepancy between preoperative assessment of middle-ear effusion and operative observation during the placement of ventilating tubes in children's ears. This study was designed to determine whether this variance is secondary to the effects of inhalation anesthesia or misinterpretation of the preoperative exam. Observations were recorded by three distinctly different methods of measurement: the surgeon, the MD-2 Impedance Analyzer, and the Acoustic Otoscope immediately before and after induction of anesthesia. These results were then analyzed and compared with the operative findings. Anesthetic induction was shown to cause alteration in the presence of middle-ear fluid in less than 10% of cases. PMID- 3336257 TI - The use of topical oral antibiotics in head and neck prophylaxis: is it justified? AB - Systemic antibiotic therapy is widely used for prophylaxis in major head and neck surgery, but the efficacy of topical oral antibiotic therapy has not been adequately investigated. A pilot, placebo-controlled, double-blind crossover study using six healthy adult male volunteers was performed to assess the influence of topical clindamycin on oral flora. Samples of saliva were cultured for aerobic and anaerobic bacteria immediately before, and at 1- and 4-hour intervals after, rinsing the mouth with a solution of either placebo or clindamycin. Quantitative analysis demonstrated significantly reduced levels of both aerobic and anaerobic bacteria after use of the topical antibiotic at both the 1- and 4-hour intervals. It is postulated that topical clindamycin, by reducing concentrations of oral flora, may also reduce the incidence of regional infection following major upper aerodigestive tract surgery. PMID- 3336259 TI - The role of needle aspiration biopsy in the selection of patients for thyroidectomy. AB - Fine needle aspiration (FNA) biopsy is gaining in popularity among all diagnostic tests used in the evaluation of patients for thyroidectomy. Its safety and accuracy have been well documented, but criteria regarding when FNA is appropriate are lacking. We retrospectively reviewed our experience with 408 consecutive patients evaluated for thyroid surgery. Two hundred seventy-three ultimately underwent thyroidectomy; 100 of these had preoperative FNA. An additional 135 patients underwent FNA without surgery. Patients who benefited from FNA were those in whom cytologic findings led to surgery for otherwise unsuspected malignancy (15), and those with asymptomatic benign nodules who avoided unnecessary thyroidectomy on the basis of FNA findings (96). FNA is superfluous when clinical conditions mandate surgery. These include nodules that arouse clinical suspicion of malignancy, massive nodules that cause aerodigestive tract compression or cosmetic disfigurement, and nodules extending into the mediastinum. All patients with asymptomatic, clinically benign thyroid nodules should undergo FNA biopsy, as approximately 50% can anticipate significant benefit from the procedure. PMID- 3336258 TI - Surgical complications following twice-a-day versus once-a-day radiation therapy. AB - With increasing numbers of radiotherapists using twice-a-day (BID) rather than conventional once-a-day (QD) radiation therapy to treat carcinomas of the head and neck, we attempted to determine whether the increased tissue reaction seen with a BID program results in greater morbidity for subsequent surgery. Postoperative complications in 24 patients receiving prior BID irradiation were compared with 37 controls receiving QD treatments. The incidence of major surgical complications for BID and QD groups was equivalent (20.8% and 18.9%, respectively). The incidence of minor complications was almost three times greater for the BID group (37.5% vs. 13.5%). Patients receiving BID radiation therapy required twice as many intraoperative transfusions (2.13 vs. 1.11) and five additional days of postoperative hospitalization (23.7 vs. 18.2). These differences are statistically significant with p-values of less than 0.5 and less than 0.1, respectively. We consider this increase in surgical morbidity to be acceptable if BID radiation therapy leads to improved tumor control. PMID- 3336262 TI - The second Joseph H. Ogura Memorial Lecture. Complications of laryngeal surgery: etiology and prevention. AB - Conservation surgery has developed into the fine-tuned, state-of-the-art procedure during the past century. With success have come the complications of stenosis, edema, infection, granulation tissue, scarring, paralysis of the laryngeal nerves, slough, aspiration, and recurrence of tumor. Some of these problems can be prevented by solid anatomical knowledge and meticulous surgery. PMID- 3336261 TI - Head and neck manifestations of sarcoidosis. AB - The records of 42 consecutive patients with biopsy-proven head and neck sarcoidosis were reviewed. A female preponderance of 7.4 to 1 was found. The average age at onset for women was higher than that for men (42 vs. 24 years). The presenting signs and symptoms were noted, and correlations between these and the incidence of abnormal chest radiograph and laboratory findings were examined. Pulmonary involvement was most common in patients with periorbital manifestations or cervical lymphadenopathy. The evaluation of patients with suspected sarcoidosis should include history and physical examination, chest radiograph, PPD and skin tests to rule out anergy, serum chemistry profile, erythrocyte sedimentation rate, and angiotensin converting enzyme level. The diagnosis is confirmed by appropriate histologic examination. Corticosteroid treatment is indicated for patients with uveitis, restrictive pulmonary disease, or other serious systemic manifestations. PMID- 3336260 TI - Ineraid (Utah) multichannel cochlear implants. AB - For the more than 200,000 individuals in the United States with a bilateral profound sensorineural hearing loss, the cochlear implant offers a means of breaking this barrier of total silence. The pioneers in prosthetic research hoped that direct stimulation of the cochlea might at least give an awareness of sound through the auditory sense. There will be a review of five patients who were consecutively implanted with the Ineraid multichannel cochlear implant, with 1 year follow-up. All individuals were postlingually deafened adults and exhibited a bilateral profound hearing loss. PMID- 3336263 TI - Effect of adenoidectomy upon children with chronic otitis media with effusion. AB - To investigate the mechanism whereby adenoidectomy influences the subsequent course of patients with chronic otitis media with effusion, we analyzed, on the basis of adenoid size, the outcomes of 476 children randomly assigned to receive, after paracentesis and aspiration of the middle ear, either no treatment, tympanostomy tubes, adenoidectomy, or both. The two groups receiving adenoidectomy did significantly better than those who did not, and the effect was independent of adenoid size. This suggests that reduction of the adenoidal bacterial reservoir may be the mechanism whereby adenoidectomy is effective. PMID- 3336264 TI - Otitis media, auditory sensitivity, and language outcomes at one year. AB - The relationship among otitis media, auditory sensitivity, and emerging language was examined in a group of 1-year-old children who were prospectively followed since birth. Pneumatic otoscopy was used to document the otologic status of the children's ears at each medical visit. There were 13 babies with normal ratings in each ear at 80% more of their visits (designated as "otitis free") and 12 babies with bilaterally positive otoscopy results at 30% or more of their first year visits (designated "otitis positive"). In comparison to the otitis free infants, the group of otitis positive babies demonstrated reduced auditory sensitivity as measured by auditory brain stem response (ABR) and poorer expressive language abilities. However, differences in receptive language were not detected. These results suggest that otitis media may have an impact on auditory sensitivity and developing language as early as 1 year of age. PMID- 3336265 TI - Analysis of pressure generation and bolus transit during pharyngeal swallowing. AB - Current pharyngeal deglutition theory has stressed the role of the pharyngeal constrictors as producing a peristaltic wave responsible for bolus propulsion through the pharynx. This thesis presents data obtained using manofluorography which supports the significance of tongue and laryngeal motion in swallowing. The usage of the term peristalsis to describe the constrictor contraction is challenged. The results of this quantitative study of swallowing in normal subjects, laryngectomized patients, and patients with restricted tongue motion show that tongue driving pressure and the negative pressure developed in the pharyngeal esophageal segment appear more important than the peristaltic-like pressure of the constrictors. Bolus transit is really dependent upon these two pressures. This model for analysis has clinical significance because it permits quantification of the pharyngeal swallowing mechanism. PMID- 3336266 TI - Treatment results for simultaneous primary squamous cell carcinomas of the head and neck. AB - Forty patients with simultaneous multiple primaries of the head and neck were treated with curative intent between June 1964 and April 1983. The primary sites were treated with radiation therapy alone or in combination with surgery. Surgery was used to salvage local failures of radiation treatment. Neck disease was treated with radiation therapy alone or with neck dissection added after completion of radiation therapy to the primary lesions. Minimum follow-up was 2 years with a range of 2 to 20 years. For the 32 patients whose primary tumors were treated with radiation alone, the 2-year local control rates for the 53 individual tumors evaluated were as follows: T1, 18/21; T2, 16/23; and T3-T4, 1/9. In the T3-T4 group, there was only one successful surgical salvage. Local control rates for disease at all primary sites in each patient according to highest T-stage were as follows: T1, 4/5; T2, 9/15; and T3-T4, 1/9. Eight patients whose primary tumors were treated with radiation and surgery are discussed. The absolute disease-free survival rate at 2 years for 40 patients was 42%. Complications of treatment are described. PMID- 3336267 TI - Evaluation of olfactory dysfunction in the Connecticut Chemosensory Clinical Research Center. AB - The olfactory test administered to patients at the Connecticut Chemosensory Clinical Research Center combines stability of outcome with sensitivity to variables known to affect olfaction (age, sex). The test, which pairs an odor threshold component with an odor identification component, readily resolves differences in function between patients and controls. It reveals differences in the distribution of functioning for various probable causes (nasal/sinus disease, postupper respiratory infection, and head trauma), proves sensitive to improvements in function caused by therapeutic intervention (ethmoidectomy, steroid administration for nasal/sinus disease), and correlates with objective signs of nasal/sinus disease (visual exam, x-ray). The two components of the test agree well, though the odor identification component seems somewhat more sensitive than the threshold component as currently designed. PMID- 3336269 TI - Parotid masses: evaluation, analysis, and current management. AB - Two hundred thirty-one sequential parotid masses seen from January 1982 to July 1986 were reviewed for their clinical presentation, diagnostic evaluation, pathologic findings, and therapeutic approach. The results were compared with the previously reported findings on parotid masses. There were 146 (63.2%) benign tumors, 50 (21.6%) malignancies, and 35 (15.2%) nonmalignant lesions. Tumors were classified according to their histopathologic diagnosis. An asymptomatic mass was the most common presentation. Radiological evaluation was mainly with computed tomography. The primary surgical procedure was parotidectomy with facial nerve preservation. A selected group of patients was referred for radiation therapy. Our study demonstrated that non-neoplastic lesions contribute a significant number of masses in the differential diagnosis of parotid tumors. Metastatic squamous cell carcinoma was the most frequently encountered malignancy. Deep lobe tumors were twice as common as previously reported. PMID- 3336268 TI - The superior laryngeal nerve: its projection to the dorsal motor nucleus of the vagus in the guinea pig. AB - The distribution of neurons in the dorsal motor nucleus of the vagus nerve (DMNV) that innervate the supraglottic and glottic areas of the larynx of the guinea pig have been studied using the horseradish peroxidase (HRP) technique. Following soaking of the superior laryngeal nerve in a solution of HRP, labeled neurons were always located ipsilaterally, at levels between the estria acustica and the caudal end of the inferior olivary nucleus. Characteristically, the neurons were small or medium in size. PMID- 3336270 TI - Endogenous digoxin-like immunoreactivity in blood is increased during prolonged strenuous exercise. AB - Digoxin-like immunoreactive factors (DLIFs) in serum may represent endogenous cardiotropic agents. We determined if blood levels of these endogenous factors changed during prolonged strenuous exercise. Total and loosely protein-bound (LPB) DLIF were measured by radioimmunoassay in the serum of nine healthy subjects during prolonged exercise to exhaustion. Mean total and LPB serum levels of DLIF increased by 72% (580 to 945 pg/mL) and 63% (53 to 91 pg/mL) over baseline values in digoxin equivalents (p less than 0.01), respectively, after three hours of exercise at 70% of VO2max. The prevalent serum nonesterified fatty acids (arachidonic, linoleic, oleic, palmitic, and stearic acids) as well as hydrocortisone did not account for the observed elevations in DLIF. Percent left ventricular fractional shortening (%FS) and mean velocity of left ventricular circumferential fiber shortening (mVCF) measured echocardiographically were lower (-18.0% and -16.4%, respectively, p less than 0.05) after exercise as compared to prior to exercise. Cardiac left ventricular dysfunction as measured by %FS did correlate with blood levels of DLIF (r = -0.680, p less than 0.02). These observations may suggest a relationship between serum levels of DLIF and cardiac fatigue. PMID- 3336271 TI - Carbonic anhydrase inhibition affects contraction of directly stimulated rat soleus. AB - We have studied the contractile parameters of directly stimulated isolated rat soleus muscles incubated in media containing the carbonic anhydrase inhibitors chlorzolamide (5.10(-4)M) or cyanate (10(-2)M). Both inhibitors caused a decrease in isometric twitch and tetanic (5s) tensions and an increase in muscle relaxation time. It is speculated that among the three types of skeletal muscle carbonic anhydrase it may be the enzyme associated with the sarcoplasmatic reticulum whose inhibition caused the observed changes in contractile parameters. PMID- 3336272 TI - Reduction of tumor growth following treatment with a glutamine antimetabolite. AB - Assessment of arterial-venous differences across transplanted methylcholanthrene induced sarcomas in rats revealed significant decreases in plasma concentrations of glutamine, serine and glucose. Treatment with the glutamine antimetabolite, acivicin, significantly reduced tumor weights by 65% at the conclusion of the experiment 34 days after tumor induction. These results suggest that glutamine is an essential metabolic substrate for tumor growth and that blockade of glutamine utilization can inhibit the growth of these transplantable sarcomas. PMID- 3336273 TI - One day of estradiol treatment enhances platelet aggregation at the site of microvascular injury without altering aggregation ex vivo. AB - Mice were implanted subcutaneously with a pellet containing 0.5 mg estradiol placebo. On the day following implantation platelet aggregation was produced in arterioles on the brain surface (pial arterioles) by injuring their endothelium in vivo with a noxious light/dye stimulus. The time between the onset of the noxious stimulus and the appearance of platelet aggregates was significantly shortened (p less than .01) in the estradiol treated mice. In contrast to this enhancement of aggregation, when platelets were tested ex vivo in platelet rich plasma (PRP), aggregation to sodium arachidonate or to ADP was not altered in estradiol treated mice. Thus the enhanced aggregation observed in injured pial arterioles of estradiol treated mice may not reflect direct effects of estradiol on the platelet itself. Rather enhanced aggregation may reflect an effect of estradiol on endothelium or adjacent tissue. This effect was produced within 24 hours of achieving pregnancy levels of estradiol. The rapidity of the effect is of interest in light of earlier studies showing a similar in vivo action following 7-14 days of high estradiol levels. The rapid effect suggests that an action on megakaryocytes is an unlikely explanation for the results. PMID- 3336274 TI - Effect of DG5128 on epinephrine and glucagon induced glucose output from the isolated perfused rat liver. AB - The effect of a specific alpha 2-adrenergic antagonist 2-[2-(4,5-dihydro-1.H imidazol-2-yl)-1-phenyl-ethyl] pyridine dihydrochloride sesquihydrate (DG5128), on the glucose output by epinephrine and/or glucagon was studied using the perfused rat liver. The administration of DG5128 alone did not affect the glucose output. However, DG5128 produced a significant inhibition of the increased glucose output when induced by 10(-6) M epinephrine alone or 10(-6) M epinephrine plus 1.4 x 10(-10) M glucagon. There were no significant changes of the glucose output by 1.4 x 10(-10) M or 7.0 x 10(-11) M glucagon alone. On the other hand, addition of 1 mU/ml insulin to the perfusate suppressed the 7.0 x 10(-11) M glucagon-induced glucose output, but failed to decrease the 1.4 x 10(-10) M glucagon effect. DG5128 suppressed further the glucagon (7.0 x 10(-11) M)-induced increase of glucose output in the presence of insulin. These results suggest that DG5128 produces a hypoglycemic effect partly through an inhibition of the increased hepatic glucose output elicited by epinephrine and glucagon. PMID- 3336275 TI - Potency of L-364,718 as an antagonist of the behavioral effects of peripherally administered cholecystokinin. AB - A new antagonist of the peripheral cholecystokinin receptor, L-364,718, was found to block the reductions in food intake and exploratory activity induced by intraperitoneal administration of cholecystokinin octapeptide sulfate. L-364,718 significantly reversed the cholecystokinin-induced reduction in feeding at doses of 10 micrograms/kg - 10 mg/kg i.p. L-364,718 significantly reversed the cholecystokinin-induced reduction in exploratory activity at doses of 500 ng/kg - 10 mg/kg i.p. The time course of antagonist activity of L-364,718 was immediate to 90 minutes after intraperitoneal administration. L-364,718 had no significant effect on food intake or exploratory activity when administered alone, over the dose range of 100 ng/kg-10 mg/kg i.p. This compound appears to be at least one hundred times more potent than proglumide or benzotript as an antagonist of the behavioral effects of peripherally administered cholecystokinin. PMID- 3336276 TI - Reversal of a trimethyltin-induced learning deficit by desglycinamide-8-arginine vasopressin. AB - Trimethyltin (TMT) is an organometal neurotoxin which produces lesions primarily in the limbic system. Selectivity seems to depend upon the dose, but the hippocampus and related entorhinal cortical structures, of importance for learning and memory, are most often described as target sites. We have previously demonstrated that subjects treated with a moderate dose of TMT prior to acquisition sessions, are unable to learn a forward autoshaping task with a 6 sec delay of reinforcement, but are capable of acquiring the same task when no delay of reinforcement is used. These data suggested that the performance deficit is one of learning (i.e. consolidation) rather than of memory (i.e. storage), retrieval, or sensorimotor impairment. To more rigorously test this hypothesis, we determined if performance of a task already learned would be impaired by the neurotoxin. Adult male Long Evans rats were given 10 acquisition sessions of 24 trials, following which TMT (6.0 mg/kg, p.o.) was administered. One month later, these rats performed the lever-touching behavior as well as controls, despite the fact that the same dose of TMT interfered with learning if given one month prior to acquisition sessions, thus confirming our hypothesis. In a second experiment we determined if the peptide analog of vasopressin, desglycinamide-8-arginine vasopressin (DGAVP), could reverse a learning deficit in a population of non learners. Rats were treated with TMT or water vehicle one month prior to autoshaping. TMT significantly retarded acquisition. After 10 sessions of 12 trials each, non-learners (i.e. rats treated with TMT that failed to associate the lever with delivery of a reinforcer) were administered saline or DGAVP (7.5 micrograms/kg, s.c.) 1 hr before sessions 11-13; treatment was discontinued prior to sessions 14 and 15. Peptide treated subjects showed evidence of acquisition and exhibited higher levels of lever-directed behavior than saline treated nonlearners. Performance was maintained after DGAVP treatment was discontinued, indicating that the learning-enhancing action of DGAVP was not transient or state dependent. PMID- 3336278 TI - Linearization of two ligand-one binding site scatchard plot and the "IC50" competitive inhibition plot: application to the simplified graphical determination of equilibrium constants. AB - A simple procedure for linearizing the curved, two ligand-one binding site Scatchard plot resulting from the presence of a constant concentration of competitive inhibitor is proposed; the same procedure may also be applied to the analysis of data derived from the "IC50" competitive inhibition experimental design. Furthermore, a useful generalization of the Cheng-Prusoff correction is presented. PMID- 3336277 TI - Bright artificial light produces subsensitivity to nicotine. AB - Bright artificial light is a treatment for seasonal depression. Eleven (11) rats were exposed to bright artificial light (11,500 lux) for two consecutive weeks. The thermic response to nicotine was measured prior to light exposure and after one and two weeks of treatment. The thermic response to nicotine at baseline was 1.69 +/- 0.25 degrees C (mean +/- SEM). The thermic response to nicotine was 0.66 +/- 0.12 degrees C (p less than 0.002) after one and +0.31 +/- 0.14 degrees C (p less than 0.000025) after two weeks of light exposure. The change in temperature was different between weeks one and two (p less than 0.000025). The exposure of animals to constant light at an intensity of 300 lux did not blunt the hypothermic response to nicotine. These findings suggest that bright artificial light, like other antidepressant treatments, produces subsensitivity of a nicotinic mechanism involved in the regulation of core temperature. PMID- 3336279 TI - The effects of subtotal pancreatectomy on renal growth in streptozotocin diabetic rats. AB - Increases in kidney size and function are characteristic features of the early stages of Type I diabetes mellitus, and may contribute to the pathogenesis of diabetic nephropathy. Other studies have shown that the relative circulating concentrations of insulin and glucagon may be regulatory to renal growth and function. In order to elucidate the role of pancreatic glucagon in diabetic renal growth, subtotal pancreatectomy was performed prior to administration of streptozotocin to rats. Glycosuria and kidney weight were significantly reduced by subtotal pancreatectomy, although creatinine clearance and blood glucose levels were not different from diabetic controls. These data suggest that hyperglucagonemia may be an important mediator of renal growth in insulinopenic diabetes mellitus. PMID- 3336281 TI - Scleromyxedema: a scleroderma-like disorder with systemic manifestations. AB - Scleromyxedema is a rare fibromucinous connective tissue disorder characterized by papular skin lesions associated with sclerosis and a serum monoclonal gammopathy. Little is known about either the natural history or the systemic manifestations of this disease. We reviewed the medical records of 19 patients with biopsy-proven scleromyxedema seen from 1950 to 1985 for evidence of systemic disease. There were 10 males and 9 females with a median age at diagnosis of 53 years. Monoclonal gammopathy was present in 13 patients. Eight patients complained of dysphagia; 3 had proximal esophageal dysfunction and 1 had total esophageal aperistalsis on barium swallow. Proximal muscle weakness was noted in 5, with an inflammatory myopathy in 3. Six patients complained of dyspnea on exertion. Of these, 5 had reduced diffusing capacity, 3 had reduced volumes, and 2 developed cor pulmonale. Pathologic changes characteristic of "scleroderma kidney" were demonstrated in 1 patient at postmortem. One patient had Raynaud's phenomenon and 2 had arthralgias/arthritis with noninflammatory synovial fluids. Although 8 of 12 patients treated with melphalan noted regression of their skin changes, no consistent improvement in the extracutaneous manifestations was demonstrated. Furthermore, 2 patients died of sepsis related to melphalan-induced myelosuppression, and 4 developed hematological malignancies following melphalan therapy. In conclusion, systemic manifestations in scleromyxedema are more prevalent than previously recognized, and can resemble those of scleroderma. Significant toxicity occurred with the use of alkylating agents in these patients, with treatment-related complications developing in 45% of patients treated with melphalan. The lack of definitive data regarding the natural history of this disease complicates the question of optimal therapy, but the use of alkylating agents should be reserved for those patients with severe debilitating skin disease. PMID- 3336280 TI - Effects of aging on pituitary and testicular luteinizing hormone-releasing hormone receptors in the rat. AB - Aging exerts profound influences on the function of the hypothalamic-pituitary testicular-axis. This work has been performed in order to verify whether, in male rats, the decreased secretion of LH and testosterone (T) occurring in old animals is reflected by modifications of luteinizing hormone-releasing hormone (LHRH) receptors at the level of the anterior pituitary and of the testes. To this purpose, the affinity constant (Ka) and the maximal binding capacity (Bmax) for the LHRH analog [D-Ser(tBu)6]des-Gly10-LHRH-N-ethylamide were evaluated, by means of a receptor binding assay, in membrane preparations derived from the anterior pituitary and testicular Leydig cells of male rats of 3 and 19 months of age. Serum levels of LH and T were measured by specific RIAs. The results obtained show that, in aged male rats, the concentration of pituitary LHRH receptors is significantly lower than that found in young animals. On the other hand, the concentration of LHRH binding sites is significantly increased on the membranes of Leydig cells of old rats. In no instance the Ka for the LHRH analog is significantly affected. Serum levels of LH and T are significantly lower in old than in young male rats. In conclusion, these results suggest that the reduced secretion of LH in old male rats may be linked, at least partially, to a decrease of the number of pituitary LHRH receptors. The impaired production of testosterone occurring in aged rats is accompanied by a significant increase of the number of testicular LHRH receptors, indicating that also the intratesticular mechanisms controlling testosterone release undergo significant alterations with aging. PMID- 3336282 TI - Sickle cell chronic lung disease: prior morbidity and the risk of pulmonary failure. AB - Sickle cell chronic lung disease (SCLD) is a prime contributor to mortality in young adult patients with sickle cell disease, especially those with sickle cell anemia (SS). Both perfusion and diffusion defects have been demonstrated, with generalized pulmonary fibrosis and disabling restrictive lung failure. We report 28 cases (25 SS, 1 S beta(0) thalassemia, 1 S beta(+) thalassemia and 1 SO-Arab) which began during the second decade of life and which ended in death by the fourth decade, after an ordered progression to pulmonary failure and cor pulmonale. Myocardial hypoxia with multifocal fibrosis and segmental infarction occurred in more than one-third of the cases and sudden death was a frequent final event. We define 4 stages of SCLD, based on pulmonary function tests, chest roentgenograms, blood gases, and noninvasive cardiac studies; each stage is 2 or 3 years in length, until death ensues in Stage 4. Case-control analysis showed that the significant risk factors associated with SCLD are 1) the total number of acute chest syndrome events in an individual before the onset of SCLD, (p = 0.0001), 2) sickle cell crisis marked by chest pain (p = 0.03) and 3) aseptic necrosis (p = 0.005). Temporal clustering of acute chest syndrome episodes frequently heralds the onset of SCLD. The pulmonary arterial bed, which has low oxygen tension and low pressure in a slow-flow system, is ideally suited to facilitate the polymerization of sickle hemoglobin, causing endothelial damage and culminating in an obstructive arteriolar vasculopathy. Identification of the significant risk factors predictive of SCLD can lead to early diagnosis of the disease; this is the only hope for effective intervention therapy. PMID- 3336283 TI - Menstrual cycle effect on plasma lipids. AB - In a study of 31 healthy women in which dietary intake and body weight were controlled, a significantly higher mean plasma cholesterol was observed in the follicular phase of the menstrual cycle compared to the luteal phase (mean difference of 8.4% during controlled dietary periods). Higher mean plasma triglycerides (mean difference of 7.4%) and lower HDL-cholesterol (mean difference of 5.8%) were also observed in the follicular phase of the controlled dietary study, although these differences were not consistently significant. PMID- 3336284 TI - Regulation of bile acid pool size and plasma lipid levels in the SHR/N-corpulent rat: influence of the level of caloric intake. AB - In the obese progeny of the SHR/N-cp strain of the rat the bile acid pool was at least twice as large as that in their lean littermates even when only 6 weeks old. The composition of the pool remained unchanged in the obese females, but in their male counterparts the proportion of cholic acid was significantly increased. Cholestyramine feeding reduced the pool size by 26% in the obese rats, but a similar effect also occurred in the lean animals. The obese rats consumed about 60% more food per day than their lean littermates. When obese females were pair-fed to the intake of their lean controls from 6 to 11 weeks of age, the bile acid pool remained significantly enlarged, although not to the same extent as in the obese rats fed ad lib. Plasma cholesterol levels were reduced but remained significantly higher than the levels in the lean animals. The marked hypertriglyceridemia exhibited by the obese rats fed ad libitum did not develop in their pair-fed counterparts. In contrast, there was a comparatively smaller reduction in plasma cholesterol and triglyceride levels in the obese rats fed cholestyramine. Hepatic steatosis persisted in the pair-fed animals as well as in those given cholestyramine. Restricting caloric intake significantly reduced the body weight gain of the obese rats but had little effect on the extent of their corpulence. These studies show that at least some of the characteristics of this congenic strain, including hypertriglyceridemia and hepatic and intestinal hypertrophy, are due mainly to excess dietary intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336285 TI - Effect of protein intake and urea on sodium excretion during inappropriate antidiuresis in rats. AB - Administration of urea to patients with the syndrome of inappropriate antidiuresis (SIAD) is thought to ameliorate hyponatremia by both producing an osmotic diuresis and diminishing ongoing natriuresis. The present study evaluated these effects in a rat model of SIAD utilizing dilutional hyponatremia induced by continuous infusion of 1-deamino-[8-D-arginine] vasopressin. Following 48 hours of sustained hyponatremia, separate groups of rats were then refed with either: (1) 5% dextrose alone, (2) a 20% protein chow, (3) an isocaloric protein deficient (0%) chow, or (4) the isocaloric protein-deficient chow supplemented with oral urea. Our results demonstrate that rats refed a 20% protein diet significantly improved their plasma [Na+] as compared to rats refed protein deficient diets, and this improvement was accompanied by decreases in natriuresis despite an increased glomerular filtration rate and an unchanged negative free water clearance. Identical effects were observed in rats refed a protein deficient diet but supplemented with oral urea, suggesting that urea generation from catabolism of dietary protein is responsible for the effect of protein refeeding to decrease urinary sodium excretion. Both the protein and urea refed rats had significantly higher inner medullary urea contents and concentrations compared to rats refed protein-deficient diets and also to rats studied immediately before protein refeeding, supporting the hypothesis that urea and dietary protein decrease natriuresis in patients with SIAD in association with increased inner medullary urea concentrations. PMID- 3336286 TI - Alterations in magnesium and zinc metabolism in thyroid disease. AB - Magnesium (Mg) and zinc (Zn) status was assessed in subjects to evaluate the effects of thyroid diseases on Mg and Zn metabolism. Plasma and red blood cell (RBC) concentration and peripheral blood mononuclear cell (MNC) content of Mg and Zn, and 24-hour urinary excretion of Mg, Zn, creatinine (Cr), calcium (Ca), sodium (Na), and potassium (K) were measured in 11 thyrotoxic, 29 hypothyroid, and 25 euthyroid control subjects. Serum albumin, alpha 2-macroglobulin, and the binding of Zn to albumin were also determined. Plasma and RBC Mg concentrations were low in half of the hyperthyroid subjects, but mean values were not significantly different from controls. Urinary excretion and clearance of Mg were lower in hypothyroid subjects, but differences were removed when expressed relative to Cr excretion and clearance. Similar patterns were noted for urinary Ca, Na, and K, suggesting that their reduced excretion reflects alterations in renal hemodynamics. Plasma Zn was lower in hypothyroid subjects and correlated with serum albumin; MNC Zn and urinary Zn were also low. Plasma Zn concentration was normal and serum albumin significantly lower in the hyperthyroid group than in the control group. Further, RBC Zn content was significantly lower in hyperthyroid subjects, and inversely related to plasma thyroxine concentration. The hyperthyroid group also excreted significantly greater amounts of Zn than controls, indicative of a catabolic process. This increased urinary loss may reflect a shift in the distribution of plasma Zn between ultrafilterable and Zn albumin complexes. In summary, this study provides evidence for marked alterations in Zn homeostasis in persons with thyroid disease. Whether the observations indicate deficiency states and have clinical implications will require further investigation. PMID- 3336288 TI - Glutamine and glucose metabolism in human peripheral lymphocytes. AB - The metabolism of glutamine and glucose in resting and concanavalin A-stimulated human peripheral lymphocytes was investigated. Glutamine was metabolized at a high rate by resting and mitogen-stimulated human peripheral lymphocytes and the major end-products of glutamine metabolism were glutamate, aspartate, CO2, and ammonia: the carbon from glutamine may contribute about 21% to respiration. Concanavalin A enhanced the formation of all end-products except glutamate, indicating that more glutamine was metabolized beyond the stage of glutamate in the mitogen-stimulated cells. Mitogenic stimulation caused an increase in the rates of glucose utilization, lactate production and 14CO2 from variously labeled [14C] glucose. Concanavalin A caused an increase in the oxidation of pyruvate as indicated by the enhanced release of 14CO2 from [2-14C]-, [3,4-14C]-, and [6-14C] glucose. When both glucose and glutamine were presented to the cells, the rates of utilization of both substrates increased and the increased rates of glucose and glutamine utilization could be accounted for mainly by increased rates of lactate and glutamate production, respectively. PMID- 3336287 TI - Extraction of epinephrine and norepinephrine by the dog pancreas in vivo. AB - This study determined the fractional extraction of epinephrine and norepinephrine by the in situ dog pancreas. Plasma samples for epinephrine measurements were taken simultaneously from the femoral artery and the superior pancreaticoduodenal vein. Pancreatic extraction of epinephrine was 73 +/- 5% when basal arterial epinephrine levels were 380 +/- 93 pg/mL, 76 +/- 4% when arterial levels were 896 +/- 123 pg/mL (epinephrine infused intravenously at 20 ng/kg/min), and 84 +/- 1% when arterial levels were 2,956 +/- 414 pg/mL (epinephrine infused intravenously at 80 ng/kg/min) suggesting that the process of epinephrine extraction by the pancreas is not saturable over this range. During a similar sampling protocol, norepinephrine was infused intravenously at 4 micrograms/kg/min; pancreatic extraction of norepinephrine was then 65 +/- 7% when arterial norepinephrine levels were 107,000 +/- 28,000 pg/mL. In separate experiments, lower rates of norepinephrine (12 to 1,200 ng/min) were infused directly into the pancreatic artery and pancreatic norepinephrine extraction was calculated; it ranged between 66% and 75%. Because the pancreas produces as well as extracts norepinephrine, a third technique was required to determine pancreatic norepinephrine extraction at the lower endogenous levels of norepinephrine; 3H-norepinephrine was infused intravenously and the arteriovenous difference of 3H-norepinephrine was measured. Fractional extraction of 3H-norepinephrine was 74 +/- 4% both in the basal state (arterial norepinephrine level = 202 +/- 44 pg/mL) and during systemic, glucopenic, stress induced by 2-deoxy-glucose (arterial norepinephrine level = 636 +/- 70 pg/mL). These data suggest that also the norepinephrine extraction process by the pancreas is not saturable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336289 TI - Cholesterol: action or caution? PMID- 3336290 TI - Computerization of a hospital waiting-list. AB - St Vincent's Hospital, Melbourne, is a 600-bed acute teaching hospital with an active waiting list. The software for a stand-alone, single-user microcomputer was developed in-house. The methods, advantages and problems that are associated with the system are presented. PMID- 3336291 TI - A comparison of plasma magnesium values in patients with acute myocardial infarction and patients with chest pain due to other causes. AB - Plasma magnesium concentrations were monitored daily in 86 patients who were admitted to a coronary care unit with a provisional diagnosis of acute myocardial infarction. Twenty-six patients had suffered a myocardial infarction, while the remainder had angina or non-cardiac chest pain. Magnesium levels were also obtained daily for five consecutive days in five normal subjects, who served as the control group. Calculations of the 95% confidence intervals on the differences between Day 1, Day 2 and individual subjects' mean plasma magnesium concentrations for the group with acute myocardial infarctions versus the group that did not have an acute myocardial infarction, the group with acute myocardial infarctions versus the reference group, and the group that did not have an acute myocardial infarction versus the reference group, and analysis of variance for the data from the three subject groups revealed no significant difference between the plasma magnesium levels of patients with an acute myocardial infarction and those with chest pain due to other causes or the normal reference population. PMID- 3336292 TI - Continuing medical education. Part 1. Introduction to the series. PMID- 3336293 TI - A bicentenary cohort: monitoring Australia's health through the next half century. PMID- 3336294 TI - What is included in clinical competence? PMID- 3336295 TI - Passive smoking and health. PMID- 3336296 TI - Managing hyperlipidaemia. PMID- 3336297 TI - A general-practice study of the efficacy and tolerability of metoprolol in mild essential hypertension. AB - The efficacy and tolerability of metoprolol (100 mg once a day) were assessed in general practice in 6713 newly-diagnosed or previously-treated hypertensive patients in an open study of eight weeks' duration. In 3534 mildly-hypertensive patients who were eligible for the efficacy analysis, the mean blood pressure level was reduced by 19/10 mmHg; 68% of the patients achieved diastolic blood pressures below 90 mmHg by the end of the assessment period. Of 6557 patients who were eligible for the tolerability analysis, only 5.6% of patients withdrew because of adverse events. The incidence of adverse events diminished considerably from the clinic assessment at four weeks (20%) to that at eight weeks (11%). At the completion of the study, 92% of the mildly-hypertensive patients were to continue with metoprolol, either as monotherapy (including 64% of patients who were receiving 100 mg once a day and 6% of patients who were receiving 50 mg once a day), or as combination therapy. Analysis of the large subgroup of mildly-hypertensive elderly patients (n = 1214) and of moderately hypertensive patients, whose diastolic pressures exceeded the set upper limits (n = 2505), showed similar efficacy and tolerability results. Sixty-eight per cent of the former and 47% of the latter demonstrated satisfactory control of blood pressure. These results show that the majority of mildly-hypertensive patients can be controlled with 50-100 mg of metoprolol once a day. PMID- 3336299 TI - The law and a physically-ill patient with anorexia nervosa: liberty versus paternalism. PMID- 3336298 TI - Vasculitis of the skin with proteinuria and mild renal failure. PMID- 3336300 TI - Fulminant postsplenectomy sepsis. AB - The vital role of a normally-functioning spleen in a host's defence against circulating microorganisms has been realized for many years. The fulminant clinical course that characterizes infection with encapsulated microorganisms in asplenic patients is highlighted in these cases of severe pneumococcal sepsis in two patients, 10 and 13 years after splenectomies for idiopathic thrombocytopenic purpura. Approaches to the acute management of septic episodes and preventive measures are discussed. Pneumococcal vaccination reduces the incidence of infection effectively in asplenic patients and has a low complication rate. Penicillin by mouth is also efficacious in this situation, but patient compliance is low. Our current practice is to offer pneumococcal vaccination to all patients who have undergone splenectomy in the past and to administer the vaccine two weeks before elective splenectomies. Asplenic patients should be educated about the potential dangers of a septic episode and should be urged to seek an early medical consultation when this occurs. PMID- 3336302 TI - Continuing medical education. PMID- 3336301 TI - Isolation of Acanthamoeba from a cerebral abscess. AB - A 55-year-old diabetic aboriginal woman presented with a two-week history of fever, altered mental state and convulsions. On the basis of computed tomographic scanning a diagnosis of cerebral abscess was made. The pus that was drained produced no bacterial growth but, on microscopy, amoebic cysts were observed. Special cultures produced a growth of Acanthamoeba. The patient appeared to respond to drainage of the abscess and antiprotozoal therapy. Unfortunately, she developed necrotizing enteritis which led ultimately to her death. Antibiotic sensitivity and pathogenicity testing suggest that the Acanthamoeba were unusually virulent. The problems of diagnosis and management are discussed. PMID- 3336304 TI - Combined antidepressant-antipsychotic drug preparations. PMID- 3336303 TI - "Involuntary" psychiatric patients and magisterial enquiries. PMID- 3336306 TI - Suicide in young persons. PMID- 3336305 TI - Hope for the mentally-ill. PMID- 3336307 TI - Anaerobic cellulitis of the arm. PMID- 3336308 TI - Reagent-strip methods for glucose. PMID- 3336309 TI - Slow-stream rehabilitation. PMID- 3336310 TI - Cosmetic surgery. PMID- 3336311 TI - Simethicone for adults at long last. PMID- 3336312 TI - Valvular surgery in Western Australia: a 15-year review. AB - Between 1970 and 1984, 1138 patients underwent the insertion of 1300 prosthetic heart valves in Western Australia; 56% received an aortic-valve replacement; 34% received a mitral-valve replacement and 10% had more than one valve replaced. Mechanical valves were used in 93% of patients before 1977, in 20% of patients between 1978 and 1982 and in 70% of patients from 1983 onwards. The 30-day mortality was 18% before 1973 and has been below 6% since 1974. The over-all, 15 year actuarial survival rate was 67%; this was not affected by age, sex, race, valvular position or the type of prosthesis. Both the 30-day mortality and 15 year survival rates were significantly worse in patients who underwent multiple valvular replacements (13% and 54%, respectively) or reoperation (16% and 58%, respectively). The major causes of death were cardiac failure and myocardial infarction (65%); endocarditis (13%); cancer (6%); and thromboembolism and bleeding (6%). The hazard rate for reoperation was low and fairly constant in patients with mechanical valves, but increased markedly after four years in patients with tissue valves. Although our experience so far suggests that survival rates are not affected by the choice of prosthesis, this may not be so in the future, as more patients with tissue valves undergo reoperation and so become exposed to an increased risk of mortality. PMID- 3336313 TI - Prevention of heat-induced illness in squash players. PMID- 3336314 TI - Human immunodeficiency virus infection in Papua New Guinea. PMID- 3336315 TI - Termination of pregnancy after an abnormal amniocentesis result. PMID- 3336316 TI - Breast-weight and industrial fatigue. PMID- 3336317 TI - The misuse of mammography in the management of breast cancer. PMID- 3336318 TI - Are herbal remedies safe. PMID- 3336319 TI - Measles vaccine failures. PMID- 3336320 TI - Non-ulcer dyspepsia: a readily-treatable disorder with no relation to Campylobacter pylori. PMID- 3336321 TI - Manifestations of Aspergillus lung disease. PMID- 3336323 TI - The great imitator. PMID- 3336322 TI - Postmenopausal osteoporosis. PMID- 3336324 TI - Stress-related illnesses. PMID- 3336326 TI - Torture in Chile. PMID- 3336325 TI - Skin cancer--childhood protection. PMID- 3336327 TI - Notification of malignant mesotheliomas. PMID- 3336328 TI - "Repetition strain injury". PMID- 3336329 TI - Education in general practice. PMID- 3336330 TI - On comparing medical school graduates. PMID- 3336331 TI - Isotopic bone-scanning to detect rib fractures. PMID- 3336332 TI - Neonatal umbilical-cord treatment. PMID- 3336333 TI - Smoking and genus Notechis. PMID- 3336334 TI - Cardiovascular risk factors and mortality. PMID- 3336335 TI - Smoking death-cards: making smoking a notifiable disease in Western Australia. PMID- 3336336 TI - The management of intracranial arteriovenous malformations. PMID- 3336337 TI - Growth and morbidity in children in a remote aboriginal community in north-west Australia. AB - As part of a wider social and environmental impact study, we have investigated the current state of health and nutrition in children who were living in a remote Aboriginal community in far north-west Australia. There was evidence of widespread mild-to-moderate malnutrition and a high prevalence of infections, particularly of the respiratory and gastrointestinal tracts, and trachoma. Low birth weight was significantly associated with the presence of undernutrition at five years of age. Our results suggest that malnutrition in utero during infancy and in early childhood and the factors which cause it may impair the growth of young Australian Aborigines permanently. PMID- 3336338 TI - Hepatic granulomas: a 15-year experience in the Royal Adelaide Hospital. AB - The clinical and pathological associations of hepatic granulomas in patients who presented to the Royal Adelaide Hospital between January 1, 1968 and February 29, 1984 were reviewed retrospectively. Cases of primary biliary cirrhosis were excluded. Of 59 patients with hepatic granulomas, clear associations with diseases were identified in 42 (71%) patients. These were sarcoidosis (seven cases), chronic liver disease (12 cases), biliary tract disease (three cases), tuberculosis (four cases), Q-fever (three cases), other infections (four cases), drug hypersensitivity (four cases) and neoplasms (five cases). Ten patients had multiple associations and five other patients presented without any clearly defined cause for granulomas. Three of these latter patients presented with an acute febrile illness, showed hepatomegaly and had abnormal results of liver function tests. These cases may represent the entity that is labeled "idiopathic granulomatous hepatitis". Two other patients abused alcohol. Granulomas were categorized morphologically as microgranulomas, macrogranulomas and lipogranulomas according to their size, organization and the presence of fat droplets. Microgranulomas were associated with diseases of short duration and less architectural disturbance of the liver parenchyma. The presence of granulomas did not confer any prognostic implication over and above that of the associated disease. PMID- 3336339 TI - Prescribing patterns in agoraphobia with panic attacks. AB - Although medication is used commonly in the treatment of agoraphobia with panic attacks, the actual drug-prescribing patterns of the medical profession have not been well studied in this condition. The present study compares the prescribing patterns of general practitioners and psychiatrists in their treatment of agoraphobia with panic attacks. The medical records of 111 agoraphobic patients with panic attacks were analysed and divided into those who were referred by general practitioners and those who were referred by psychiatrists. Over all, in the treatment of agoraphobia with panic attacks, general practitioners prescribed drugs less often than did psychiatrists. They used fewer combinations of drugs and tended to prescribe tricyclic antidepressant agents in doses which generally are considered to be below the therapeutic range. This finding would suggest that general practitioners are less effective than are psychiatrists in prescribing for this condition as judged by current practice, although they are less likely to prescribe combinations of drugs--a practice which might well be to their credit. PMID- 3336340 TI - Continuing medical education. Part 2. Needs assessment in continuing medical education. PMID- 3336341 TI - Idiopathic chronic fatigue and myalgia syndrome (myalgic encephalomyelitis): some thoughts on nomenclature and aetiology. AB - Myalgic encephalomyelitis is a misnomer that describes epidemics of probable hysterical illness and bears no definite relationship to chronic fatigue and myalgia syndrome. The relationship of idiopathic fatigue syndromes to fatigue syndromes after well-defined viral illnesses such as glandular fever is also unclear. Detailed studies of muscle histochemistry and biochemistry in idiopathic chronic fatigue and myalgia syndrome do not support a defect in intermediate metabolism. The aetiology of this syndrome is unknown and it is not yet clear whether it has an organic or a non-organic basis. PMID- 3336342 TI - Human behaviour and the ethics of coercion. AB - There is an assumption that legislation against unhealthy behaviour would be unethical, or at best unenforceable and counterproductive. However, the ethics of coercion depend on the manner in which such coercion is introduced, the essential precondition being wide, favourable community consensus. Two recent Australian examples have been the Victorian seat-belt legislation and the Tasmanian hydatid campaign. Hydatid control in Tasmania began with a voluntary campaign in the farming community which led to a popular demand for government intervention. In response to community pressure, the State Department of Agriculture introduced control measures with a stepwise increase in coercion that began with a voluntary dog-testing programme, and proceeded to a compulsory test and later to the quarantine of infected dogs. Ultimately, quarantine was extended to premises with a higher-than-average residual prevalence in sheep. Today, hydatid disease has almost disappeared in livestock. As no new human case of hydatid disease has been diagnosed in a person of under 10 years of age since 1972, or in one of under 20 years of age since 1976, human infection probably ceased by 1972. Legislation today could control the composition of processed food (for example, the salt content), or establish compulsory testing for human immunodeficiency virus antibodies. The necessary consensus could be the specific objective of health education during a voluntary phase. PMID- 3336343 TI - Breast cancer in Australia: occurrence, risk factors, preventability and screening. PMID- 3336344 TI - Intracerebral haematoma mimicking intracranial neoplasm at computed tomography. AB - The diagnosis of a typical acute intracerebral haematoma is comparatively specific with computed tomography. Three cases are presented to illustrate computed tomographic similarities between intracerebral haematomas and intracranial neoplasms. In the appropriate clinical setting, an incorrect diagnosis may be reached unless these similarities are borne in mind. PMID- 3336346 TI - Treatment of sexually transmitted diseases. PMID- 3336345 TI - Phaeochromocytoma and cardiomyopathy. AB - This case report describes a patient who presented with severe biventricular cardiac failure and shock, whose cardiac function returned to normal after the removal of a noradrenaline-secreting benign phaeochromocytoma. A catecholamine induced cardiomyopathy with cardiogenic shock, rather than catecholamine-mediated peripheral vasoconstriction alone, is postulated as a mechanism to account for the marked hypoperfusion. PMID- 3336347 TI - Selective inactivation of four rat liver microsomal androstenedione hydroxylases by chloramphenicol analogs. AB - The steroid androstenedione has been shown to be a valuable tool for the study of the selective inactivation of cytochrome P-450 isozymes in intact rat liver microsomes. The validity of this approach was investigated using microsomes, purified cytochrome P-450 isozymes, antibodies to particular cytochromes P-450, and the known mechanism-based inactivator chloramphenicol. Enzyme inactivation and antibody inhibition studies show that microsomes from both phenobarbital- and non-phenobarbital-treated rats are needed to accurately monitor the inactivation of the major phenobarbital-inducible cytochrome P-450 isozyme (PB-B) and of the major constitutive androstenedione 16 alpha-hydroxylase (UT-A). Similar experiments indicate that, although isozyme P-450g does catalyze the 6 beta hydroxylation of androstenedione in a reconstituted system, this cytochrome appears to make only a minimal contribution to microsomal 6 beta-hydroxylase activity, which reflects instead the activity of pregnenolone-16 alpha carbonitrile-induced isozymes. With these parameters investigated, initial enzyme inactivation studies showed that the antibiotic chloramphenicol caused different rates of NADPH-dependent enzyme inactivation among the four androstenedione hydroxylases monitored (16 beta greater than 6 beta greater than 16 alpha greater than 7 alpha). Based on these data, 12 chloramphenicol analogs were examined, and the results with these compounds show that their selectivity as cytochrome P-450 inactivators is a function of at least three structural features: 1) the number of halogen atoms, 2) the presence of a para-nitro group on the phenyl ring, and 3) substitutions on the ethyl side chain. For example, the compound N-(2 phenethyl)dichloroacetamide was shown to reversibly inhibit but not inactivate the cytochrome(s) P-450 responsible for androstenedione 6 beta-hydroxylase activity, whereas N-(2-p-nitrophenethyl) and N-(1,2-diphenethyl)dichloroacetamide rapidly inactivated the 6 beta-hydroxylase. The ability to monitor the activity of multiple isozymes with a single substrate should allow the development of a systematic approach to the design of selective inactivators of rat liver cytochromes P-450. PMID- 3336348 TI - Glucuronidation of 7-hydroxycoumarin in periportal and pericentral regions of the lobule in livers from untreated and 3-methylcholanthrene-treated rats. AB - Rates of production of 7-hydroxycoumarin glucuronide were measured in specific zones of the liver lobule using micro-light guides placed on periportal and pericentral regions on the surface of livers from untreated and 3 methylcholanthrene-treated rats. Livers were perfused with sulfate-free buffer under normoxic conditions and fluorescence of free 7-hydroxycoumarin was monitored. The formation of nonfluorescent 7-hydroxycoumarin glucuronide was then inhibited completely by perfusion with N2-saturated perfusate containing 20 mM ethanol. The difference between fluorescence readings under normoxic and hypoxic conditions was used to calculate rates of glucuronidation. Maximal rates of glucuronidation (11.9-13.5 mumol/g/hr) did not differ significantly in periportal and pericentral regions in livers from either 3-methylcholanthrene-treated or untreated rats. In all regions of the liver lobule, glucuronidation was half maximal with about 20 microM 7-hydroxycoumarin. Glucuronosyltransferase assayed in lyophilized tissue sections with saturating concentrations of UDPGA (9 mM) was 2.3-fold greater in pericentral than in periportal areas in livers from untreated rats. In livers from 3-methylcholanthrene-treated rats, activities were similar in periportal and pericentral regions but were 4- to 7-fold higher than values from untreated rats. In addition, glucuronosyltransferase activity assayed in native microsomes with physiological concentrations of UDP-glucuronic acid (UDPGA) (0.4 mM) with UDP-N-acetylglucosamine (0.3 mM) was 2-fold higher in preparations from 3-methylcholanthrene-treated than untreated rats. Thus, 3 methylcholanthrene treatment increased glucuronosyltransferase activity in vitro but did not alter rates of glucuronide formation in periportal and pericentral regions of the liver lobule of intact liver. Infusion of epinephrine (50 nM) into perfused livers from untreated and 3-methylcholanthrene-treated rats increased rates of glucuronidation by about 35%. Since epinephrine probably acts by increasing the supply of the cofactor UDPGA due to increased breakdown of glycogen, it follows that UDPGA supply limits rates of glucuronidation in perfused livers from both untreated and 3-methylcholanthrene-treated rats. PMID- 3336349 TI - Hydrophobicity of the tetrabenazine-binding site of the chromaffin granule monoamine transporter. AB - The catecholamine uptake inhibitor tetrabenazine (TBZ) binds to a high affinity site on the chromaffin granule membrane, presumably on the monoamine transporter. The hydrophobicity of the TBZ-binding site was investigated by comparing the potency of drugs to displace [3H]dihydrotetrabenazine (TBZOH), a ligand of the TBZ-binding site, with the lipophilicity of these drugs reflected by their octanol/buffer apparent partition coefficient (P o/b). Drugs tested were five substrates of the transporter, seven TBZ derivatives, and the inhibitors reserpine, haloperidol, and chlorpromazine. The validity of apparent P o/b as an index of lipophilicity was shown by measuring drug partitioning between buffer and chromaffin granule membranes. For most of the inhibitors tested, octanol/buffer and membrane/buffer apparent partition coefficients were correlated. For substrates of uptake and TBZ derivatives, the potency of a compound to displace [3H]TBZOH from its binding site was correlated to its apparent P o/b. This relationship was valid over a range of 5 orders of magnitude. These data are interpreted as indicating that the TBZ-binding site is hydrophobic and is in equilibrium with the ligand present in the membrane phase, and that substrates and TBZ derivatives are characterized by an equal intrinsic affinity for this site of about 1 microM. The 3-fold difference in affinity observed between alpha- and beta-diastereoisomers of TBZOH was accounted for by a similar difference in apparent P o/b. Reserpine, haloperidol, and chlorpromazine have much lower intrinsic affinity for the TBZ-binding site. PMID- 3336350 TI - Correlation of alpha- and beta-rotameric forms of 2-substituted octahydrobenzo[f]quinoline dopamine congeners with high and low affinity states of the anterior pituitary dopamine receptor and prolactin inhibition. AB - The flexible dopamine (DA) molecule exists in one or the other of its two conformational extremes (alpha- or beta-rotamer) and its receptor in the anterior pituitary gland exists in a high and a low affinity state. A series of novel, rigid DA congeners (2-substituted octahydrobenzo[f]quinolines) was synthesized and used to investigate the conformation of DA preferred by its anterior pituitary receptor and the significance of recognition of the two affinity states to the inhibition of prolactin (PRL) secretion. Analysis of competition curves of congeners for [3H]spiperone binding to bovine anterior pituitary membranes was used to calculate affinity constants. Congeners in the beta-rotamer conformation showed a biphasic competition curve as observed for DA. The curves were resolved into high (nM) and low (microM) affinity binding sites. This biphasic binding could be converted to monophasic low affinity binding in the presence of a nonhydrolyzable GTP analog. The congeners in the alpha-rotameric conformation showed monophasic low affinity binding. The potency of congeners to suppress PRL release was evaluated in cell cultures of dispersed bovine anterior pituitary. Congeners recognizing the high affinity binding site were 100-fold more potent in suppressing PRL release than those recognizing only low affinity binding sites. Dihydroxy congeners versus monohydroxy congeners and cyanomethyl group substituted versus methylthiomethyl substituted congeners occupied greater proportions of high affinity binding sites. Increasing proportions of high affinity sites occupied increased the potency of the congener to suppress PRL release. These results suggest that the beta-rotameric conformational extreme of DA is preferred by its receptor in the anterior pituitary gland and that the high affinity state of this receptor is functionally important in mediating the inhibition of PRL secretion. PMID- 3336351 TI - The biooxidation of cytotoxic ellipticine derivatives: a key to structure activity relationship studies? AB - In the family of ellipticine derivatives, those with an amino-phenol or a masked amino-phenol structure are among the most cytotoxic compounds. Preliminary studies on 9-hydroxy- or 9-methoxyellipticines have shown that these molecules behave as "pro-alkylating" agents. In order to rationalize the "biooxidative alkylation" process for various ellipticine derivatives, we report in the present article (i) their electrochemical oxidation parameters, (ii) their biochemical oxidation, (iii) the ability of the oxidized forms to form adducts with nucleophiles, (iv) the biological activities, and (v) the electronic properties of oxidized forms. We present some possible correlations between the oxidizability, the electrophilicity of the oxidized derivatives, and the biological activities of the corresponding drugs. PMID- 3336352 TI - Comparison of nonerythroid alpha-spectrin genes reveals strict homology among diverse species. AB - The spectrins are a family of widely distributed filamentous proteins. In association with actin, spectrins form a supporting and organizing scaffold for cell membranes. Using antibodies specific for human brain alpha-spectrin (alpha fodrin), we have cloned a rat brain alpha-spectrin cDNA from an expression library. Several closely related human clones were also isolated by hybridization. Comparison of sequences of these and other overlapping nonerythroid and erythroid alpha-spectrin genes demonstrated that the nonerythroid genes are strictly conserved across species, while the mammalian erythroid genes have diverged rapidly. Peptide sequences deduced from these cDNAs revealed that the nonerythroid alpha-spectrin chain, like the erythroid spectrin, is composed of multiple 106-amino-acid repeating units, with the characteristic invariant tryptophan as well as other charged and hydrophobic residues in conserved locations. However, the carboxy-terminal sequence varies markedly from this internal repeat pattern and may represent a specialized functional site. The nonerythroid alpha-spectrin gene was mapped to human chromosome 9, in contrast to the erythroid alpha-spectrin gene, which has previously been assigned to a locus on chromosome 1. PMID- 3336353 TI - Effect of protein synthesis inhibition on gene expression during early development of Dictyostelium discoideum. AB - Several genes which are deactivated on the initiation of development of Dictyostelium discoideum were identified by differential screening of various cDNA libraries. These genes have in common a decrease in the steady-state levels of their corresponding mRNAs on the onset of development and as development proceeds. When development was carried out in the absence of protein synthesis by inhibition with cycloheximide, the decrease in mRNA levels for most genes (V genes) was normal or slightly accelerated. For about 5% of the genes (H genes), however, cycloheximide caused an apparent induction of expression, as revealed by a slight or dramatic increase in mRNA levels, instead of the normal decrease. This effect was due to inhibition of protein synthesis and not to cycloheximide per se. The induction was found to be due to an enhancement of the transcription rate; normal rates of transcription for the H genes were dependent on continued protein synthesis during vegetative growth and development. Thus, two general regulatory classes exist for deactivation of gene expression on initiation of development, one of which is dependent on and one of which is independent of protein synthesis. Analysis of expression of these genes in mutant strains which are aggregation deficient allowed the classes to be subdivided further. Taken together, these characterizations allow several distinct regulatory mechanisms to be identified that are involved in the deactivation of gene expression on the onset of development in D. discoideum. PMID- 3336354 TI - DNA affinity labeling of adenovirus type 2 upstream promoter sequence-binding factors identifies two distinct proteins. AB - A rapid affinity labeling procedure with enhanced specificity was developed to identify DNA-binding proteins. 32P was first introduced at unique phosphodiester bonds within the DNA recognition sequence. UV light-dependent cross-linking of pyrimidines to amino acid residues in direct contact at the binding site, followed by micrococcal nuclease digestion, resulted in the transfer of 32P to only those specific protein(s) which recognized the binding sequence. This method was applied to the detection and characterization of proteins that bound to the upstream promoter sequence (-50 to -66) of the human adenovirus type 2 major late promoter. We detected two distinct proteins with molecular weights of 45,000 and 116,000 that interacted with this promoter element. The two proteins differed significantly in their chromatographic and cross-linking behaviors. PMID- 3336355 TI - Transformation by the src oncogene alters glucose transport into rat and chicken cells by different mechanisms. AB - Transformation of both rat and chicken fibroblasts by the src oncogene leads to a four- to fivefold increase in the rate of glucose transport and in the level of the glucose transporter protein. We have previously shown that, with chicken embryo fibroblasts, transformation leads to a reduction in the rate of degradation of the transporter, with little or no increase in the rate of its biosynthesis. We now show that, with the rat-1 cell line, the opposite result was obtained. src-induced transformation led to an increase in transporter biosynthesis, with little effect on turnover. A src-induced increase in transporter mRNA entirely accounted for the increase in biosynthesis of the protein. By contrast, in chicken embryo fibroblasts, the level of transporter mRNA was low and was not induced to rise by src transformation. Thus, src induced an increase in the level of the glucose transport protein by fundamentally different mechanisms in chicken embryo fibroblasts and rat-1 cells. To test whether this difference was due to rat-1 cells being an immortalized cell line, we measured transporter mRNA levels in primary fibroblast cultures from rat embryos and in parallel cultures transformed by src. Transporter mRNA was inducible by src in these cells. Thus, the difference in mRNA inducibility between chicken and rat cells is not due to immortalization. PMID- 3336356 TI - A developmentally regulated membrane protein gene in Dictyostelium discoideum is also induced by heat shock and cold shock. AB - We have analyzed the expression of the Dictyostelium gene P8A7 which had been isolated as a cDNA clone from an early developmentally regulated gene. The single genomic copy generated two mRNAs which were subject to different control mechanisms: while one mRNA (P8A7S) was regulated like the cell-type-nonspecific late genes, the other one (P8A7L) was induced during development, when cells were allowed to attach to a substrate, and when cells were subjected to stress, such as heat shock and cadmium. Interestingly the same induction was also observed with cold shock. RNA processing was inhibited by heat and cold shock, leading to nuclear accumulation of a precursor. The translated region of the cDNA was common to both mRNAs and encoded an unusually hydrophobic peptide with the characteristics of a membrane protein. PMID- 3336357 TI - Cloning and characterization of a cDNA encoding transformation-sensitive tropomyosin isoform 3 from tumorigenic human fibroblasts. AB - We isolated a cDNA clone from the tumorigenic human fibroblast cell line HuT-14 that contains the entire protein coding region of tropomyosin isoform 3 (Tm3) and 781 base pairs of 5'- and 3'-untranslated sequences. Tm3, despite its apparent smaller molecular weight than Tm1 in two-dimensional gels, has the same peptide length as Tm1 (284 amino acids) and shares 83% homology with Tm1. Tm3 cDNA hybridized to an abundant mRNA of 1.3 kilobases in fetal muscle and cardiac muscle, suggesting that Tm3 is related to an alpha fast-tropomyosin. The first 188 amino acids of Tm3 are identical to those of rat or rabbit skeletal muscle alpha-tropomyosin, and the last 71 amino acids differ from those of rat smooth muscle alpha-tropomyosin by only 1 residue. Tm3 therefore appears to be encoded by the same gene that encodes the fast skeletal muscle alpha-tropomyosin and the smooth muscle alpha-tropomyosin via an alternative RNA-splicing mechanism. In contrast to Tm4 and Tm5, Tm3 has a small gene family, with, at best, only one pseudogene. PMID- 3336358 TI - Preferential amplification of rearranged sequences near amplified adenylate deaminase genes. AB - In a previous study of three independent families of mutants selected for overproduction of adenylate deaminase (AMPD), we were not able to isolate a cDNA probe for the gene and so could not demonstrate its amplification directly. In addition to overproduction of AMPD, four proteins of unknown function, designated W, X, Y1, and Y2, accumulated, and by using the corresponding cDNA probes, we demonstrated amplification of all four genes. In independent mutant clones, sometimes all and sometimes only a subset of these genes were amplified. Assuming that all five genes are linked, the pattern of their coamplification suggested a genetic map in which AMPD lies between W and Y1. We show here that a two-step chromosome walk joins the W and Y1 genes, that the AMPD gene is the only expressed sequence between them, and that its amplification is indeed responsible for overproduction of the AMPD protein. In the course of this work, we cloned and studied two novel joints which mark rearrangements on either side of the AMPD gene. Each joint was generated independently in a single first-step mutant at single or low copy number. Remarkably, each joint was amplified preferentially in every second- and third-step mutant derived from the first-step line in which it was originally present, suggesting that the two independent rearrangements each generated amplification-prone structures. PMID- 3336360 TI - Developmentally controlled telomere addition in wild-type and mutant paramecia. AB - We analyzed sites of macronuclear telomere addition at a single genetic locus in Paramecium tetraurelia. We showed that in homozygous wild-type cells, differential genomic processing during macronuclear development resulted in the A surface antigen gene being located 8, 13, or 26 kilobases upstream from a macronuclear telomere. We describe variable rearrangements that occurred at the telomere 8 kilobases from the A gene. A mutant (d48) that forms a telomere near the 5' end of the A gene was also analyzed. This mutant was shown to create simple terminal deletions; telomeric repeats were added directly to the truncated wild-type A gene sequence. In both the mutant and wild-type cells, the telomeric sequences (a mixture of C4A2 and C3A3 repeats) were added to various sequences within a specific 200- to 500-base-pair region rather than to a single site. No similarities were found in the primary sequences surrounding the telomere addition sites. The mutation in d48 changed the region of telomere addition at the A gene locus; this is the first example in ciliates of a mutation that affects the site of telomere addition. PMID- 3336359 TI - A 29-nucleotide DNA segment containing an evolutionarily conserved motif is required in cis for cell-type-restricted repression of the chicken alpha-smooth muscle actin gene core promoter. AB - A series of 5' deletion mutations of the upstream flanking sequences of the chicken alpha-smooth muscle (aortic) actin gene was prepared and inserted into the chloramphenicol acetyltransferase expression vector pSV0CAT. Deletion recombinants were transfected into fibroblasts, which actively express the alpha smooth muscle actin gene, and primary myoblast cultures, which accumulate much lower quantities of alpha-smooth muscle actin mRNAs. The first 122 nucleotides of 5'-flanking DNA were found to contain a "core" promoter capable of accurately directing high levels of transcription in both fibroblasts and myotubes. The activity of this core promoter is modulated in fibroblasts by a "governor" element(s) located at least in part between nucleotides -257 and -123. This region contains sequences potentially conserved between mammalian and avian alpha smooth muscle actin genes as well as one of a pair of 16-base-pair inverted CCAAT box-associated repeats which are conserved among all chordate muscle actin genes examined to date. A smaller DNA segment (-151 to -123) containing these upstream CCAAT box-associated repeats was sufficient to suppress expression of the core promoter in muscle cultures, suggesting that the upstream CCAAT box-associated repeats play a negative role in the alpha-smooth muscle actin gene promoter. PMID- 3336362 TI - mRNA stability plays a major role in regulating the temperature-specific expression of a Tetrahymena thermophila surface protein. AB - Synthesis of the serotype H3 (SerH3) surface antigen is temperature dependent and responds within 1 h to a change in incubation conditions (G.A. Bannon, R. Perkins Dameron, and A. Allen-Nash, Mol. Cell. Biol. 6:3240-3245, 1986). Recently, a Tetrahymena thermophila cDNA clone (pC6; D.W. Martindale and P.J. Bruns, Mol. Cell. Biol. 3:1857-1865, 1983) has been shown to be homologous to a portion of the SerH3 mRNA (F.P. Doerder and R.L. Hallberg, personal communication), and it was shown that the cellular levels of this RNA rapidly decreased when cells were shifted from 30 to 41 degrees C (R.L. Hallberg, K.W. Kraus, and R.C. Findly, Mol. Cell. Biol. 4:2170-2179, 1984). These observations indicate that synthesis of the SerH3 protein is highly regulated in response to temperature and led us to initiate studies to determine the mechanism(s) by which SerH3 gene expression is controlled. Using pC6 as a hybridization probe for the SerH3 mRNA, we have determined that (i) the level of SerH3 protein synthesis is directly correlated with the amount of SerH3 message available for translation; (ii) there is, at most, a twofold difference between the relative transcription rates of SerH3 genes at 30 and 40 degrees C; (iii) the SerH3 mRNA half-life in cells incubated at 30 degrees C is greater than 1 h, whereas the half-life in cells incubated at 40 degrees C is only approximately 3 min. These results demonstrate that Tetrahymena SerH3 surface protein expression is regulated by mRNA abundance. Furthermore, the major mechanism controlling mRNA abundance is a dramatic temperature-dependent change in SerH3 mRNA stability. PMID- 3336361 TI - Induction of mutation in mouse FM3A cells by N4-aminocytidine-mediated replicational errors. AB - To explore the potential use of a nucleoside analog, N4-aminocytidine, in studies of cellular biology, the mechanism of mutation induced by this compound in mouse FM3A cells in culture was studied. On treatment of cells in suspension with N4 aminocytidine, the mutation to ouabain resistance was induced. The major DNA replicating enzyme in mammalian cells, DNA polymerase alpha, was used to investigate whether the possible cellular metabolite of N4-aminocytidine, N4 aminodeoxycytidine 5'-triphosphate (dCamTP), can be incorporated into the DNA during replication. Using [3H]dCamTP in an in vitro DNA-synthesizing system, we were able to show that this nucleotide analog can be incorporated into newly formed DNA and that it can serve as a substitute for either dCTP or dTTP. dCamTP in the absence of dCTP maintained the activated calf thymus DNA-directed polymerization of deoxynucleoside triphosphates as efficiently as in its presence. Even in the presence of dCTP, dCamTP was incorporated into the polynucleotide. When dCamTP was used as a single substrate in the poly(dA) oligo(dT)-directed polymerase reaction, it was incorporated into the polynucleotide fraction. The extent of incorporation was 4% of that of dTTP incorporation when dTTP was used as a single substrate. Even in the presence of dTTP, dCamTP incorporation was observed. A copolymer containing N4-aminocytosine residues was shown to incorporate guanine residues opposite the N4 aminocytosines. However, we were unable to observe adenine incorporation opposite N4-aminocytosine in templates. These cell-free experiments show that an AT-to-GC transition can take place in the presence of dCamTP during DNA synthesis, strongly suggesting that the mutation induced in the FM3A cells by N4 aminocytidine is due to replicational errors. PMID- 3336364 TI - Production and characterization of biologically active recombinant beta nerve growth factor. AB - DNA fragments encoding either rat or chicken beta nerve growth factor (NGF) were inserted in the expression vector p91023(B) for transient expression in COS cells. The two NGF constructs produced RNA transcripts and proteins of the predicted sizes. Conditioned media from the transfected cells stimulated neurite outgrowth from cultured chicken embryo sympathetic ganglia. The results show that the rat or chicken NGF gene can direct the synthesis of a biologically active NGF protein after transfection of COS cells. PMID- 3336363 TI - Human hTM alpha gene: expression in muscle and nonmuscle tissue. AB - We have isolated a cDNA clone from a human skeletal muscle library which contains the complete protein-coding sequence of a skeletal muscle alpha-tropomyosin. This cDNA sequence defines a fourth human tropomyosin gene, the hTM alpha gene, which is distinct from the hTMnm gene encoding a closely related isoform of skeletal muscle alpha-tropomyosin. In cultured human fibroblasts, the hTM alpha gene encodes both skeletal-muscle- and smooth-muscle-type alpha-tropomyosins by using an alternative mRNA-splicing mechanism. PMID- 3336365 TI - The cap of both miniexon-derived RNA and mRNA of trypanosomes is 7 methylguanosine. AB - Most, if not all, trypanosome mRNAs have the same 35-base sequence at their 5' terminus which is derived from a short RNA (medRNA) probably by the process of trans-splicing. It is of interest, evolutionarily and mechanistically, to determine the chemical structure of the 5' terminus of the precursor (medRNA) and product (mRNA). We demonstrate here that the cap structure of both is most probably 7-methylguanosine in a 5',5' triphosphate linkage, consistent with a precursor/product relationship. PMID- 3336367 TI - DNase I- and micrococcal nuclease-hypersensitive sites in the human apolipoprotein B gene are tissue specific. AB - We have mapped the DNase I- and micrococcal nuclease-hypersensitive sites present in the 5' end of the human apolipoprotein B (apo-B) gene in nuclei from cells expressing or not expressing the gene. Four DNase I-hypersensitive sites were found in nuclei from liver-derived HepG2 cells and intestine-derived CaCo-2 cells, which express the apo-B gene, but not in HeLa cells, which do not. These sites are located near positions -120, -440, -700, and +760 base pairs relative to the transcriptional start site. Undifferentiated CaCo-2 cells exhibited another site, near position -540. Six micrococcal nuclease-hypersensitive sites were found in nuclei from HepG2 and CaCo-2 cells, but not in HeLa cells or free DNA. These sites are located near positions -120, -390, -530, -700, -850, and +210. HepG2 cells exhibited another site, near position +460. Comparison of the DNA sequence of the 5' flanking regions of the human and mouse apo-B genes revealed a high degree of evolutionary conservation of short stretches of sequences in the immediate vicinity of each of the DNase I- and most of the micrococcal nuclease-hypersensitive sites. PMID- 3336369 TI - Characterization of Staphylococcus epidermidis mutants sensitive to ultraviolet radiation. AB - Five UV-sensitive mutants obtained by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment of the Staphylococcus epidermidis W5 strain were characterized phenotypically by assaying their UV- and MNNG-sensitivities, lysogenic inducibility, host-cell reactivation and Weigle reactivation capacities. The results were compared with those of well-characterized Escherichia coli strains, permitting the identification of: 2 mutants that behave as Uvr- Umu-; 1 mutant that appears analogous to Uvr-; 1 mutant that resembles LexA- and 1 mutant that exhibits a RecA- phenotype. The study of these mutants can contribute to the understanding of the repair mechanisms in S. epidermidis. PMID- 3336366 TI - The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer. AB - Muscle creatine kinase (MCK) is induced to high levels during skeletal muscle differentiation. We have examined the upstream regulatory elements of the mouse MCK gene which specify its activation during myogenesis in culture. Fusion genes containing up to 3,300 nucleotides (nt) of MCK 5' flanking DNA in various positions and orientations relative to the bacterial chloramphenicol acetyltransferase (CAT) structural gene were transfected into cultured cells. Transient expression of CAT was compared between proliferating and differentiated MM14 mouse myoblasts and with nonmyogenic mouse L cells. The major effector of high-level expression was found to have the properties of a transcriptional enhancer. This element, located between 1,050 and 1,256 nt upstream of the transcription start site, was also found to have a major influence on the tissue and differentiation specificity of MCK expression; it activated either the MCK promoter or heterologous promoters only in differentiated muscle cells. Comparisons of viral and cellular enhancer sequences with the MCK enhancer revealed some similarities to essential regions of the simian virus 40 enhancer as well as to a region of the immunoglobulin heavy-chain enhancer, which has been implicated in tissue-specific protein binding. Even in the absence of the enhancer, low-level expression from a 776-nt MCK promoter retained differentiation specificity. In addition to positive regulatory elements, our data provide some evidence for negative regulatory elements with activity in myoblasts. These may contribute to the cell type and differentiation specificity of MCK expression. PMID- 3336368 TI - The cell-specific enhancer of the mouse transthyretin (prealbumin) gene binds a common factor at one site and a liver-specific factor(s) at two other sites. AB - We previously defined two distinct cell-specific DNA elements controlling the transient expression of the transthyretin gene in Hep G2 (human hepatoma) cells: a proximal promoter region (-202 base pairs [bp] to the cap site), and a far upstream cell-specific enhancer located between 1.6 and 2.15 kilobases (kb) 5' of the cap site (R. H. Costa, E. Lai, and J. E. Darnell, Jr., Mol. Cell. Biol. 6:4697-4708, 1986). In this report, we located the effective transthyretin enhancer element within a 100-bp region between 1.96 and 1.86 kb 5' to the mRNA cap site. In Hep G2 nuclear extracts, three protein-binding sites within this minimal enhancer element were identified by gel mobility and methylation protection experiments. Each binding site was required for full enhancer activity in Hep G2 transient expression assays. Competition experiments in protein-binding assays suggested that two of the three sites were recognized by a similar factor and that the protein interaction with the third site was different. The nuclear protein(s) which bound to the two homologous sites was found mainly or only in cells of hepatic origin, suggesting an involvement of this region in the cell specific function of this enhancer. The nuclear protein(s) recognizing the third enhancer region was also found in HeLa and spleen cells. PMID- 3336370 TI - Phenotypic heterogeneity within the first complementation group of UV-sensitive mutants of Chinese hamster cell lines. AB - A DNA-repair mutant was characterized that has the extraordinary and interesting properties of extreme sensitivity to UV killing combined with a high level of nucleotide excision repair. The mutant V-H1 isolated from the V79 Chinese hamster cell line appeared very stable, with a reversion frequency of about 3.5 X 10(-7). Genetic complementation analysis indicates that V-H1 belongs to the first complementation group of UV-sensitive Chinese hamster ovary (CHO) mutants described by Thompson et al. (1981). This corresponds with data on cross sensitivity and mutation induction after UV irradiation published by this group. Surprisingly, the mutant V-H1 shows only slightly reduced (to approximately 70%) unscheduled DNA synthesis (UDS) after UV exposure, while the other two mutants of this complementation group are deficient in UDS after UV. In agreement with the high residual UDS, in V-H1 also the amount of repair replication in response to UV treatment is relatively high (approximately 50%). It has also been shown that the incision step of the nucleotide excision pathway takes place in V-H1 (with a lower rate than observed in wild-type cells), whereas another mutant (UV5) of the same complementation group is deficient in incision. This heterogeneity within the first complementation group indicates that the repair gene of this complementation group may have more than one functionally important domain or that the gene is not involved in the incision per se but is involved in e.g. preferential repair of active genes. PMID- 3336371 TI - Two DNA endonuclease activities from normal human and xeroderma pigmentosum chromatin active on psoralen plus ultraviolet light treated DNA. AB - DNA endonuclease activities from the chromatin of normal human and xeroderma pigmentosum, complementation group A (XPA), lymphoblastoid cells were examined on DNA treated with 8-methoxypsoralen (8-MOP) or 4,5',8-trimethylpsoralen (TMP) plus long wavelength ultraviolet (UVA) light, which produce monoadducts and DNA interstrand cross-links, and angelicin plus UVA light, which produces mainly monoadducts. 9 chromatin-associated DNA endonuclease activities were isolated from normal and XPA cells and assayed for activity on PM2 bacteriophage DNA that had been treated with 8-MOP or TMP in the dark and then exposed to UVA light. Unbound psoralen was removed by dialysis and a second dose of UVA light was given. Cross-linking of DNA molecules was confirmed by alkaline gel electrophoresis. In both normal and XPA cells, two DNA endonuclease activities were found which were active on 8-MOP and TMP plus UVA light treated DNA. One of these endonuclease activities, pI 4.6, is also active on intercalated DNA and a second one, pI 7.6, is also active on UVC (254 nm) light irradiated DNA. The major activity against angelicin plus UVA light treated DNA in both normal and XPA cells was found in the fraction, pI 7.6. The levels of activity of both of these fractions on all 3 psoralen-damaged DNAs were similar between normal and XPA cells. These results indicate that in both normal and XPA cells there are at least two different DNA endonucleases which act on both 8-MOP and TMP plus UVA light treated DNA. PMID- 3336372 TI - Effects of X-irradiation at different times during development on the yield of somatic mutations in melanocytes of the mouse. AB - The effect of 2.0 Gy X-irradiation at different times during foetal and early post-natal development on the resultant somatic mutation frequency was investigated by scoring for changes in follicular melanocyte morphology (nucleofugal vs. nucleopetal) in mice heterozygous for the recessive coat colour mutations dilute (d) and leaden (ln). Two peaks were observed following X irradiation on days 12.5 and 17.5 post coitus (p.c.). The biomodal character of the mutation frequency with time of X-irradiation may be related to changes in the dynamics of the melanocyte population with foetal age. Nonetheless, the results validate the treatment time used in the pilot study (Searle and Stephenson, 1982) as the most sensitive to the induction of somatic mutations within the follicular melanocyte population. PMID- 3336373 TI - Karyotypic abnormality of the X chromosome is rare in mutant HPRT-lymphocyte clones. AB - Lymphocyte clones mutated at the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) locus on the X chromosome were studied by synchronization and G banding to determine the proportion of mutant clones having visible karyotypic change. 47 spontaneously mutant clones, 17 mutant clones induced by X-irradiation and 33 wild-type clones were studied. All clones were karyotypically normal except for 1 clone induced by X-irradiation in which an interstitial deletion of the short arm of the X chromosome had been inserted into the long arm of the same chromosome between q23 and q24; this change may have been coincidental or may have resulted in a position effect mutation. It was concluded that the great majority of mutations were not associated with a visible chromosome abnormality. This conclusion complements molecular studies which suggest that gene changes at the HPRT locus in HPRT- mutants generally extend over segments of DNA too small to be resolved by karyotypic analysis. PMID- 3336374 TI - Evidence for uptake of 8-methoxypsoralen and 5-methoxypsoralen by cellular nuclei. AB - The fluorescent appearance of oral mucosa cells treated with 8-methoxypsoralen (8 MOP) and 5-methoxypsoralen (5-MOP) was observed by means of fluorescence microscopy. Fluorescence at the nuclei was weakened in 8-MOP-treated cells, while it was intensified in 5-MOP-treated cells. These findings were consistent with changes in the fluorescence intensities on association of the psoralen derivatives with DNA in aqueous solution. This intensity change of fluorescence and also the blue shift of the fluorescence maximum of the derivatives on association suggested that the environment around the psoralen molecules is as little polar as methanol. From the results of these fluorescence microscopic observations and spectroscopic analysis of fluorescence of derivatives interacting with DNA during equilibrium dialysis, we concluded that 8-MOP, as well as 5-MOP, is incorporated by nuclei of human cells. PMID- 3336375 TI - Measurement of DNA breakage in spermiogenic germ-cell stages of mice exposed to ethylene oxide, using an alkaline elution procedure. AB - DNA breakage in spermiogenic stages of the mouse was studied after exposure to ethylene oxide (EtO), using an alkaline elution technique. At daily intervals over a 23-day period following i.p. injection of 100 mg EtO/kg, mature spermatozoa were recovered from treated ([3H]dThd-labeled) and control ([14C]dThd labeled) animals, lysed together on polycarbonate filters, and the DNA was eluted with a high pH (12.2) buffer. Elution of germ-cell DNA from EtO-exposed animals increased (more DNA strand breaks) in stages sensitive to the genetic effects of EtO (late spermatids to early spermatozoa). The stage-related pattern of EtO induced DNA breakage paralleled the pattern of sperm alkylation and protamine alkylation found to be produced by EtO in an earlier study (Sega and Owens, 1987). At 9 days posttreatment (sperm sampled were in late-spermatid stages at the time of EtO exposure) the amount of sperm DNA eluted did not change significantly over a pH range of 11.6-12.8, indicating that, at the time of assay, DNA breaks were already present in the sperm. PMID- 3336376 TI - Induction of translocations in mouse spermatogonia after fractionated exposure to 60Co gamma-rays. AB - Male mice of the Q strain were exposed to 60Co gamma-rays at 2 Gy and 2 X 2 Gy separated by increasing time intervals (from 0 min to 4 min). The chromosome translocations induced in spermatogonia were scored at diakinesis-metaphase I. A significant decrease of the translocation frequency at time intervals higher than 2 min was observed, confirming results obtained with plant materials. PMID- 3336377 TI - A comment on the quantitative relationship between micronuclei and chromosomal aberrations. PMID- 3336379 TI - Treatment of severe chloroquine poisoning. AB - No therapy has been proved to be effective for patients with severe chloroquine poisoning, which is usually fatal. In a retrospective study of 51 cases, we found that ingestion of more than 5 g of chloroquine was an accurate predictor of a fatal outcome, and therefore chose this dose as the criterion for severe chloroquine poisoning. We selected as a control group 11 consecutive patients who had ingested more than 5 g of chloroquine between July 1983 and December 1985. We then undertook a prospective study to determine whether a better outcome could be obtained with immediate mechanical ventilation and the administration of diazepam and epinephrine. Eleven consecutive patients who ingested more than 5 g of chloroquine in 1986 received this combination therapy. Ten of these patients survived, whereas only one control had survived (P = 0.0003). There was no significant difference between the combination-therapy and control groups in age (29 +/- 3 vs. 27 +/- 2 years), amount of chloroquine ingested (7.5 +/- 0.5 vs. 8.5 +/- 0.8 g), systolic arterial pressure (74 +/- 2 vs. 74 +/- 3 mm Hg), or QRS duration (0.14 +/- 0.01 vs. 0.14 +/- 0.01 second). In our combination-therapy group, blood chloroquine levels ranged from 40 to 80 mumol per liter, whereas a literature search showed that no patient in whom blood levels were more than 25 mumol per liter had survived. These preliminary data suggest that combining early mechanical ventilation with the administration of diazepam and epinephrine may be effective in the treatment of severe chloroquine poisoning. PMID- 3336378 TI - Liquid-holding experiments with human lymphocytes. III. Experiments with G0 and G1 cells. AB - Liquid holding (LH) experiments were performed with human peripheral lymphocytes treated in the G0 (G0-LH) or the G1 (G1-LH) phase of the cell cycle with diepoxybutane (DEB) or methylnitrosourea (MNU). In the G0-LH system, treatment with DEB but not with MNU led to a lowering of the frequencies of sister chromatid exchanges (SCE). In the G1-LH system treatment with both chemicals led to a lowering of the SCE frequencies during the LH. These results are concluded to mean that lesions induced by DEB but not by MNU can be repaired in G0 cells and that G1 cells can repair both DEB and MNU induced lesions. PMID- 3336380 TI - Effect of nicotine chewing gum in combination with group counseling on the cessation of smoking. AB - We studied the effectiveness of chewing gum containing nicotine, in combination with group counseling, for subjects who were attempting to stop smoking. We used the Horn-Russell scale, based on a smoking questionnaire, to measure dependence on cigarettes; 173 smokers were grouped as highly dependent on nicotine or as having medium to low degrees of dependence. In a randomized double-blind study, the 60 highly dependent smokers were given gum containing 4 mg of nicotine (n = 27) or 2 mg of nicotine (n = 33), and the 113 smokers with medium or low dependence were given gum containing 2 mg of nicotine (n = 60) or a placebo gum (n = 53). All smokers took part in group counseling. In the highly dependent group, abstinence from cigarettes was chemically verified after six weeks, one year, and two years; 81.5 percent, 44.4 percent, and 33.3 percent of the subjects given gum containing 4 mg of nicotine were abstinent after those follow-up periods; the rates of abstinence were 54.5 percent, 12.1 percent, and 6.1 percent, respectively, for the subjects given gum containing 2 mg of nicotine. In the group with medium or low dependence, the rates of abstinence after the same periods were 73.3 percent, 38.3 percent, and 28.3 percent for the subjects given gum containing 2 mg of nicotine and 41.5 percent, 22.6 percent, and 9.4 percent for those given placebo gum. The differences in outcomes were significant at the 5 percent level for all comparisons, with the exception of the 2-mg nicotine gum versus the placebo gum at one year. This study indicates that the effectiveness of nicotine gum is not due to a placebo effect and that it is related to dose. The use of nicotine gum in appropriate doses should be helpful to persons who are attempting to stop smoking. PMID- 3336381 TI - Out-of-hospital cardiac arrest. Use of electrophysiologic testing in the prediction of long-term outcome. AB - We examined the role of electrophysiologic testing in the prediction of long-term outcome in 166 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction. Ventricular arrhythmias were inducible in 131 patients (79 percent) at base line and were suppressed by antiarrhythmic drugs or surgery (or both) in 91 of 127 (72 percent). During a median follow-up period of 21 months, cardiac arrest recurred in 29 patients: 11 (12 percent) of the 91 in whom inducible arrhythmias had been suppressed (including 5 patients in whom treatment had been discontinued), 12 (33 percent) of the 36 in whom inducible arrhythmias persisted, and 6 (17 percent) of the 35 in whom arrhythmias could not be induced at the initial electrophysiologic study. Cox survival analysis identified the following three variables as significant independent predictors of recurrent cardiac arrest: persistence of inducible ventricular arrhythmias (relative risk, 3.97 [95 percent confidence interval, 1.80 to 8.75], P = 0.0006), a left ventricular ejection fraction of 30 percent or less (relative risk, 2.60 [1.21 to 5.53], P = 0.0138), and the absence of cardiac surgery (relative risk, 4.20 [0.99 to 17.77], P = 0.0512). We conclude that electrophysiologic testing is useful in quantifying the subsequent risk of cardiac arrest among survivors of out-of-hospital cardiac arrest. PMID- 3336382 TI - Diphtheria outbreaks in immunized populations. PMID- 3336383 TI - Ethics and communication in do-not-resuscitate orders. PMID- 3336384 TI - Transplantation of fetal substantia nigra and adrenal medulla to the caudate nucleus in two patients with Parkinson's disease. PMID- 3336385 TI - Cancer surveillance in patients with ulcerative colitis. PMID- 3336387 TI - Hair clippings in the external auditory canal: ah, there's the rub. PMID- 3336386 TI - "A matter of influence": graduate medical education and commercial sponsorship. PMID- 3336388 TI - Desegregation of hospitals and medical societies in North Carolina. PMID- 3336389 TI - Case records of the Massachusetts General Hospital. Case 2-1988. A 55-year-old man with innumerable gastric polyps and recent melena. PMID- 3336390 TI - A perspective on type A behavior and coronary disease. PMID- 3336391 TI - Specialization in the Yellow Pages. PMID- 3336392 TI - Myocardial infarction in a patient with hemophilia treated with DDAVP. PMID- 3336393 TI - Autoantibody-mediated acquired deficiency of C1 inhibitor. PMID- 3336394 TI - Bacteremic pneumonia caused by penicillin-resistant pneumococci. PMID- 3336395 TI - Administration of human diploid-cell rabies vaccine in the gluteal area. PMID- 3336396 TI - Type A behavior and mortality from coronary heart disease. AB - The relation of behavior (Type A or Type B) to the morbidity and mortality of coronary heart disease (CHD) is still debated. We studied the survival of 257 male patients with CHD from the initial, 8.5-year phase of the Western Collaborative Group Study to see whether behavior type--as assessed by a structured interview before the CHD event--was related to subsequent CHD mortality. Behavior type was not related to mortality in 26 patients who died within 24 hours of the coronary event. However, of the 231 patients who survived for 24 hours, the mortality rate associated with CHD among 160 Type A patients studied during an average 12.7 years was 19.1 per 1000 person-years. This was unexpectedly lower than the corresponding rate of 31.7 among 71 Type B patients who were followed for an average of 11.5 years (P = 0.04). In a proportional hazards survival analysis, which controlled for variable follow-up time, the type of initial coronary event, and traditional risk variables, the relative CHD associated mortality rate among Type A as compared with Type B patients was 0.58 (P = 0.03; 95 percent confidence interval, 0.35 to 0.96). The lower mortality among Type A subjects occurred in both younger and older subgroups but was more pronounced in patients whose initial diagnosis was symptomatic myocardial infarction rather than silent myocardial infarction or angina pectoris. This apparent advantage associated with Type A behavior is surprising and needs confirmation, but the results do indicate that patients with CHD and a Type A behavior pattern are not at increased risk for subsequent CHD mortality. PMID- 3336397 TI - Risk of second cancers after treatment for Hodgkin's disease. AB - We estimated the risk of second cancers among 1507 patients with Hodgkin's disease treated at Stanford University Medical Center since 1968. Eight-three second cancers occurred more than one year after diagnosis, as compared with 15.9 expected on the basis of rates in the general population (relative risk, 5.2; 95 percent confidence interval, 4.2 to 6.5). The mean (+/- SE) 15-year actuarial risk of all second cancers was 17.6 +/- 3.1 percent, of which 13.2 +/- 3.1 percent was due to solid tumors. The risk of leukemia appeared to reach a plateau level of 3.3 +/- 0.6 percent at 10 years, whereas non-Hodgkin's lymphoma continued to increase, to 1.6 +/- 0.7 percent by the end of the follow-up period. The risk of solid tumors did not vary significantly according to treatment category, with the array of neoplasms resembling that previously observed in populations exposed to radiation and in immunosuppressed groups. The risk of leukemia, although elevated after radiation therapy alone (relative risk, 11; 95 percent confidence interval, 1.2 to 38), was much higher after either adjuvant chemotherapy (relative risk, 117; 95 percent confidence interval, 69 to 185) or chemotherapy alone (relative risk, 130; 95 percent confidence interval, 26 to 380). These data suggest that the risk of solid tumors after therapy for Hodgkin's disease continues to increase with time. PMID- 3336398 TI - Survival after cardiopulmonary resuscitation in babies of very low birth weight. Is CPR futile therapy? AB - We conducted a retrospective study of outcome after cardiopulmonary resuscitation (CPR) in babies of very low birth weight. Of 158 such babies (birth weight, less than 1500 g) admitted to a neonatal intensive care unit in 1985, 49 (31 percent) underwent CPR. Low birth weight, low Apgar scores, birth asphyxia, pulmonary interstitial emphysema, hyaline membrane disease, and severe intraventricular hemorrhage were associated with the need for CPR. None of the 38 babies who received CPR in the first three days of life survived. Four of the 11 babies who received CPR after the first 72 hours survived. Three of the four survivors had residual neurologic deficits. Survival rates after CPR in infants of very low birth weight are lower than those in older children or adults. CPR may therefore be considered a nonvalidated therapy in this population. If the results of our study are confirmed, CPR should not be instituted automatically in very-low-birth weight babies as though it were a validated treatment. Instead, it should be administered upon parents' advance informed consent to experimental treatment. PMID- 3336399 TI - Right ventricular cardiomyopathy and sudden death in young people. AB - From 1979 to 1986, we conducted postmortem studies of 60 persons under 35 years of age who had died suddenly in the Veneto Region of northeastern Italy. Unexpectedly, we found that 12 subjects--7 males and 5 females ranging in age from 13 to 30 years--had morphologic features of right ventricular cardiomyopathy. This disorder had not been diagnosed or suspected before the subjects died. In five cases, sudden death was the first sign of disease; the remaining seven subjects had a history of palpitation, syncopal episodes, or both, and in five of those seven, ventricular arrhythmias had previously been recorded on electrocardiographic examination. Ten of the subjects had died during exertion. At autopsy, the subjects' heart weights were normal or moderately increased. Two main histologic patterns were identified--a lipomatous transformation or a fibrolipomatous transformation of the right ventricular free wall (6 cases each); in all cases, the left ventricle was substantially spared. Signs of myocardial degeneration and necrosis, with or without inflammatory infiltrates, were occasionally observed. These findings indicate that right ventricular cardiomyopathy, the cause of which is still unknown, may be more frequent than previously thought. At least in this area of Italy, it may represent an important cause of sudden death among young people. PMID- 3336400 TI - Differences in platelet enzyme activity between alcoholics and nonalcoholics. AB - Blood platelets are an accessible tissue that reflects the activity of many enzymes found in the brain. To investigate the possible effect on such enzymes of long-term consumption of large quantities of ethanol, we assayed the activities of two enzymes, monoamine oxidase and adenylate cyclase, in platelet membranes of men with alcoholism and controls matched for sex and age. We also compared these two groups in terms of the inhibition of platelet monoamine oxidase activity by ethanol in vitro (400 mM), and in terms of the stimulation of adenylate cyclase activity by various agents. There was no significant difference in monoamine oxidase activity between the alcoholics and the controls. However, the inhibition of monoamine oxidase by ethanol was significantly higher in the platelets of alcoholics. The basal activity of adenylate cyclase was the same in platelets from the alcoholics and the controls, but the platelet adenylate cyclase activity after stimulation with guanine nucleotide, cesium fluoride, or prostaglandin E1 was significantly lower in alcoholics. These differences were not associated with age, race, smoking, or illicit drug use, and there was no significant correlation with the duration of problems with alcohol. The changes were long-lasting; cesium fluoride-stimulated adenylate cyclase activity was lower in alcoholic subjects who had abstained from alcohol for one to four years. Discriminant analysis showed that the use of values for the inhibition of monoamine oxidase activity by ethanol and cesium fluoride-stimulated adenylate cyclase activity correctly classified 75 percent of the alcoholics and 73 percent of the controls. These measures may be of value either as indexes of excessive alcohol consumption or as an indication of a predisposition to alcoholism. PMID- 3336402 TI - Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy. AB - Susceptibility to diabetic nephropathy may be related to a predisposition to arterial hypertension. We have studied the activity of sodium-lithium countertransport in red cells, a marker of risk for essential hypertension, in white European adults with insulin-dependent diabetes and diabetic nephropathy, a matched group of patients with diabetes without renal disease, and nondiabetic patients with renal disease. Measures of metabolic control and concentrations of plasma free insulin and growth hormone were similar in the two diabetic groups. The degree of impairment in renal function was similar in the diabetic and nondiabetic patients with renal disease. Body-mass index and plasma potassium concentrations were similar in all three groups. Diastolic blood pressure was elevated to a similar degree in the two groups with renal disease, as compared with that in the diabetic patients without renal disease. The rates of sodium lithium countertransport in red cells were significantly higher in the diabetic patients with renal disease (mean +/- SD, 0.55 +/- 0.19 mmol of lithium per liter of red cells per hour) than in the diabetic patients without renal disease (0.33 +/- 0.16; P less than 0.005) and in the nondiabetic patients with renal disease (0.31 +/- 0.14; P less than 0.001). Predisposition to hypertension, as indicated by elevated sodium-lithium countertransport activity in red cells, may serve as a marker for the risk of renal disease in patients with insulin-dependent diabetes. PMID- 3336403 TI - Incidence of unwarranted implantation of permanent cardiac pacemakers in a large medical population. AB - Because of allegations that the implantation of many permanent cardiac pacemakers has been unjustified, we reviewed the indications for all new pacemakers implanted at 30 hospitals in Philadelphia County between January 1 and June 30, 1983, and paid for by Medicare. Complete chart data were evaluated for 382 implants. We determined whether the indications for implantation were appropriate and adequately documented on the basis of standard clinical practice. Implants were classified as possibly indicated primarily because of inadequate diagnostic evaluation (63 percent) or inadequate documentation of an accepted indication (36 percent). Implants were classified as not indicated primarily because a rhythm abnormality was incorrectly identified as a justifiable indication (84 percent). We found that 168 implants (44 percent) were definitely indicated, 137 (36 percent) possibly indicated, and 77 (20 percent) not indicated. Unwarranted implantation was both prevalent (73 percent of hospitals had an incidence of 10 percent or more) and independent of the type of hospital (university teaching, university-affiliated, and community hospitals). The additional tests most often required to clarify the need for a pacemaker in inadequately evaluated cases included electrophysiologic studies (37 percent) and ambulatory monitoring (31 percent). We conclude that in a large medical population in 1983, the indications for a considerable number of permanent pacemakers were inadequate or incompletely documented. PMID- 3336401 TI - Predisposition to hypertension and susceptibility to renal disease in insulin dependent diabetes mellitus. AB - Only one third of patients with juvenile-onset insulin-dependent diabetes seem to be susceptible to diabetic nephropathy. To test whether this susceptibility is related to a predisposition to hypertension, we investigated the association of nephropathy with markers of risk for hypertension. We randomly selected 89 patients with insulin-dependent diabetes from a roster of children and adolescents who were seen between 1968 and 1972 at about the time the diagnosis was made. These 89 patients were recalled for examination, as young adults, in 1986 and 1987. Patients with nephropathy (cases, n = 33) were compared with controls without nephropathy (n = 56). Having a parent with hypertension tripled the risk of nephropathy (odds ratio, 3.7; 95 percent confidence interval, 1.4 to 10.1). Moreover, cases had significantly higher values for maximal velocity of lithium-sodium countertransport in red cells than controls (mean maximal velocity +/- SE, 0.51 +/- 0.04 vs. 0.38 +/- 0.02 mmol per liter of cells per hour; P less than 0.05). The excess risk associated with both these indicators of a predisposition to hypertension was evident principally in patients with poor glycemic control during their first decade of diabetes; the odds ratios were 4.5 (95 percent confidence interval, 1.1 to 18.7) for patients with a parental history of hypertension and 7.7 (95 percent confidence interval, 1.8 to 33.8) for patients with a maximal velocity of lithium-sodium countertransport greater than or equal to 0.35 mmol per liter of cells per hour. We conclude that the risk of renal disease in patients with juvenile-onset insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Predisposition to hypertension appears to increase susceptibility for renal disease principally in patients with poor glycemic control. PMID- 3336404 TI - Right ventricular cardiomyopathy: another cause of sudden death in the young. PMID- 3336405 TI - Biologic-marker studies in alcoholism. PMID- 3336406 TI - Pacemaker mania. PMID- 3336407 TI - Transfusion-associated hepatitis and AIDS. PMID- 3336409 TI - Disjunction of the mitral annulus in floppy mitral valve. PMID- 3336408 TI - Failure of voluntary testing for human immunodeficiency virus to identify infected parturient women in a high-risk population. PMID- 3336410 TI - Prevention by choline of the depletion of membrane phosphatidylcholine by a cholinesterase inhibitor. PMID- 3336412 TI - Nodular and diffuse types of lymphocyte predominance Hodgkin's disease. AB - The nodular form of lymphocyte predominance Hodgkin's disease has been shown to be immunophenotypically distinct from the histologically diffuse form and from other types of Hodgkin's disease. We undertook a clinicopathological study of 73 cases to determine whether any clinical differences between the nodular and diffuse subtypes could be discerned. Patients with the diffuse form (n = 41) tended to have a course similar to that of other types of Hodgkin's disease; there were few relapses and only two deaths due to Hodgkin's disease. In contrast, patients with the nodular form (n = 32) had significantly more relapses, which were independent of stage or treatment and equally distributed up to 10 years after initial therapy. Despite the frequent relapses, patients with the nodular form had an indolent course, and there was only one death due to Hodgkin's disease. There were seven fatal second cancers and two non-neoplastic treatment-related deaths, equally distributed between the nodular and diffuse groups. We conclude that nodular lymphocyte predominance Hodgkin's disease may have important clinical as well as immunophenotypic differences from other forms of Hodgkin's disease, and that patients with this condition should be followed carefully because of the possibility of late relapse. PMID- 3336413 TI - Are continuing studies of metabolic control and microvascular complications in insulin-dependent diabetes mellitus justified? The Diabetes Control and Complications Trial. PMID- 3336411 TI - Human immunodeficiency virus infection among patients attending clinics for sexually transmitted diseases. AB - To assess the prevalence and associated risk factors for human immunodeficiency virus (HIV) infection in patients attending inner-city clinics for sexually transmitted diseases in Baltimore, we screened 4028 patients anonymously, of whom 209 (5.2 percent) were seropositive for HIV. HIV-seropositivity rates were higher among men (6.3 percent) than women (3.0 percent) (P less than 0.001) and among blacks (5.0 percent) than whites (1.2 percent) (P less than 0.02). Among men, but not women, HIV seroprevalence increased markedly and steadily up to the age of 40. In men, HIV seropositivity was independently associated with increased age, black race, a history of homosexual contact, and the use of parenteral drugs. In women, a history of parenteral drug use or of being a sexual partner of a bisexual man or parenteral drug user were independently predictive of HIV seropositivity. In men, HIV seropositivity was also associated with a history of syphilis or a reactive serologic test for syphilis, and in women, with a history of genital warts. Since these associations were independent of the type and number of reported sexual partners, they raise the possibility that sexually transmitted diseases that disrupt epithelial surfaces may be important in the transmissibility of HIV. In addition, on a self-administered questionnaire, one third of HIV-infected men and one half of infected women did not acknowledge previous high-risk behavior for HIV exposure. These data suggest that patients at clinics for sexually transmitted diseases represent a group at high risk for HIV infection, and that screening, counseling, and intensive education should be offered to all patients attending such clinics. PMID- 3336414 TI - AIDS-related Kaposi's sarcoma in New York City in 1977. PMID- 3336415 TI - Decreased catecholamines in the adrenal medulla of patients with parkinsonism. PMID- 3336416 TI - Dexamethasone in primary supratentorial intracerebral hemorrhage. PMID- 3336417 TI - Academic geriatrics for the year 2000. PMID- 3336418 TI - Instilling eye drops in the involuntary blinker. PMID- 3336419 TI - Prenatal management of 746 pregnancies at risk for congenital toxoplasmosis. AB - When infection with Toxoplasma gondii occurs during pregnancy, there is a risk that the parasite will cause severe congenital toxoplasmosis. We developed a method of diagnosing and treating congenital toxoplasmosis in utero. Diagnosis was based on the identification of maternal acute infection, followed by culture of fetal blood and amniotic fluid, testing of fetal blood for toxoplasma-specific IgM and nonspecific measures of infection, and ultrasound examination of the fetal brain. Treatment included the administration of antibiotics to all mothers with confirmed acute infection during pregnancy, with more intensive antibiotic treatment of those who had infected fetuses and who chose to continue the pregnancy. We report a prospective study of 746 documented cases of maternal toxoplasma infection, in which the infants were followed for at least three months. Infection was diagnosed antenatally in 39 of 42 fetuses. Twenty-four of the 39 pregnancies were terminated, and 15 were continued. All the mothers were treated with spiramycin throughout pregnancy; if fetal infection was demonstrated, pyrimethamine and either sulfadoxine or sulfadiazine were added to the regimen. Of the 15 fetuses with congenital toxoplasmosis who were carried to term, all but 2, who had chorioretinitis, remained clinically well during follow up. We conclude that prenatal diagnosis of congenital toxoplasmosis is practical and that prenatal therapy in women who wish to continue their pregnancies reduces the severity of the manifestations of the disease. PMID- 3336421 TI - Penicillin and the marked decrease in morbidity and mortality from rheumatic fever in the United States. AB - There has been a marked decline in mortality due to rheumatic fever in the United States. We present evidence for the important role of penicillin in changing the severity of rheumatic carditis, beginning about 1946. Since that year, mortality due to rheumatic carditis has rapidly decreased to zero at the hospital we studied (House of the Good Samaritan, Boston), the rate of loss of all murmurs in patients at the study hospital accelerated simultaneously and exceeded 40 percent by 1970, and the rates of decline in national mortality due to rheumatic carditis accelerated fourfold with the advent of antibiotics. These data, together with reports of recent outbreaks of rheumatic fever, emphasize the importance of continued efforts to diagnose and treat Group A streptococcal pharyngitis. PMID- 3336420 TI - The prevalence of infection with human immunodeficiency virus over a 10-year period in rural Zaire. AB - In 1985 we tested 659 human serum samples, collected in the remote Equateur province of Zaire in 1976, for antibody to human immunodeficiency virus (HIV). Five (0.8 percent) were positive, and HIV was isolated from one of these. Follow up investigations in 1985 revealed that three of the five seropositive persons had died of illnesses suggestive of acquired immunodeficiency syndrome (AIDS), and two remained healthy but seropositive. In 1986, a serosurvey we conducted using a cluster-sampling technique in the same region showed a seroprevalence of 0.8 percent in 389 randomly selected residents. The seroprevalence in 283 prostitutes was 11 percent. Patients with AIDS were identified in various hospitals in the province. Risk factors for AIDS included a greater than average number of sexual partners and residence outside the area. We believe that the long-term stability of HIV infection in residents of rural Zaire suggests that social change may have promoted the spread of AIDS in Africa. PMID- 3336423 TI - Toxoplasmosis: the time has come. PMID- 3336422 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 5-1988. A 34-year-old man with a destructive sacral lesion and a left gluteal mass. PMID- 3336424 TI - Transformation of American health care. The role of the medical profession. PMID- 3336425 TI - Lead poisoning in automobile radiator mechanics. PMID- 3336426 TI - The efficacy of oral zinc therapy as an alternative to penicillamine for Wilson's disease. PMID- 3336427 TI - Lupus psychosis and anti-ribosomal P protein antibodies. PMID- 3336428 TI - Case 30-1987: cytology of pulmonary blood samples. PMID- 3336430 TI - Rich rewards for medical prize-winners. PMID- 3336429 TI - Prevention of nosocomial infections by isolation procedures. PMID- 3336431 TI - Unauthorized environmental release cleared by NIH. PMID- 3336432 TI - Vaccine project is scrapped. PMID- 3336433 TI - DNA fingerprinting database to finger criminals. PMID- 3336434 TI - Muscle-bound bacteria and weak worms. PMID- 3336436 TI - How to avoid jet lag. PMID- 3336435 TI - A bacterial way of life. PMID- 3336437 TI - Perception of three-dimensional structure from motion in monkey and man. AB - Information on motion is important for the determination of the three-dimensional (3-D) structure of the environment for both human and non-human primates. For example, if a person were to close one eye and look at an evenly illuminated, irregularly shaped object, he would be unlikely to guess its shape correctly. But if the object is moved about, the correct shape immediately becomes apparent. Little is known about how the primate visual system actually does this, although various theories have been proposed. We have developed novel, highly controlled motion stimuli to use with psychophysical and physiological techniques to study how 3-D structure is obtained from motion. We show that the Rhesus monkey can detect 3-D structure from motion in the same way as human subjects. Furthermore, the dependence of both species on certain parameters of the display shows that information is integrated both spatially and temporally for this higher visual function. PMID- 3336438 TI - Brain-derived neurotrophic factor prevents neuronal death in vivo. AB - Developing vertebrate neurons are thought to depend for their survival on specific neurotrophic proteins present in their target fields. The limited availability of these proteins does not allow the survival of all neurons initially innervating a target, resulting in the widely observed phenomenon of naturally occurring neuronal death. Although a variety of proteins have been reported to promote the survival of neurons in tissue culture, the demonstration that these proteins increase neuronal numbers and/or decrease neuronal death in vivo has only been possible with nerve growth factor (NGF). The generalization of the concept that neurotrophic proteins regulate neuronal survival during normal development critically depends on the demonstration that the survival of neurons in vivo can be increased by the administration of a neurotrophic protein different from NGF. We report here that this is the case with brain-derived neurotrophic factor, a protein of extremely low abundance purified from the central nervous system. PMID- 3336439 TI - A neuronal mechanism for sensory gating during locomotion in a vertebrate. AB - The response of the foot to touch during walking depends on whether it is in the air or on the ground. In most animals, reflex responses to external stimuli are similarly adapted to their timing in the locomotor cycle, but there is only fragmentary information about the neural mechanisms involved. In arthropods, reflex modulation can occur in the sensory receptors themselves and in neurons that discharge during locomotion. By recording with dye-filled microelectrodes from neurons in the spinal cord of frog embryos, we describe reflex modulation at the level of sensory interneurons. Sensory inputs from skin receptors excite a specific class of spinal sensory interneuron whose activity leads to reflex bending of the body away from the stimulus. During swimming, these inputs are gated by rhythmic postsynaptic inhibition, so that sensory drive reaches motor neurons only at phases in the locomotor cycle when the resulting contraction would likewise turn the embryo away from the stimulated side. Such gating of sensory pathways could be a general feature of all locomotor systems where responses to sensory stimuli need to be adapted to the phase of locomotion. PMID- 3336440 TI - A pseudoknotted RNA oligonucleotide. AB - The diverse functions of RNA, which include enzymatic activities, regulatory roles in transcription and translation, are made possible by tertiary structure. Computer algorithms can predict the secondary structure of an RNA molecule using free-energy parameters for base pairing and stacking, loops and bulges. However, with the exception of transfer RNA, little is known about the structures and thermodynamics of interactions involved in the tertiary structure of RNA. Recently, it has been proposed that a novel form of RNA folding called pseudoknotting occurs at the 3' end of certain viral RNAs from plants. A pseudoknot involves intramolecular pairing of bases in a hairpin loop with a few bases outside the stem of the loop to form an additional stem and loop region (Fig. 1). If each stem contained a full helical turn, a true knot would be formed. We present evidence from single-strand specific (S1) and double-strand specific (V1) nuclease digestion, that a short RNA oligonucleotide (19 nucleotides long) adopts a stable pseudoknotted structure. The nuclease digestion and thermodynamic properties of this oligonucleotide were compared with those of oligonucleotides which form hairpin structures containing the two possible stem regions in the pseudoknot. These results show that appropriate sequences can form pseudoknots and indicate that pseudoknots are a significant type of local tertiary structure which must be considered in the folding of complex RNA molecules. PMID- 3336441 TI - Visual evoked potentials in the investigation of "blindsight". AB - We recorded long-latency visual evoked potentials in four patients with homonymous hemianopias, one of whom had clinical evidence of "blindsight." Stimuli consisted of different words that appeared randomly and at a constant angle to either side of the center of a TV screen, and subjects responded to one previously specified word (the "target") by finger extension. Target stimuli in the intact hemifield elicited a well-formed P3 response in all subjects, whereas stimuli in the blind field produced no such response except in the subject with blindsight. In addition, the earlier potentials in this subject were larger with stimulation of the blind hemifield than the intact field. By contrast, a P100 response was present only with stimulation of the intact field in this subject. These results indicate that cognitive processing of visual stimuli can occur even when subjective awareness of such stimuli is absent, and suggest that such processing occurs independently of the geniculostriate pathway. PMID- 3336442 TI - Palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations. AB - Upward and downward gaze palsy was measured by a magnetic search coil technique and correlated with neuropathologic findings in a patient with a unilateral midbrain infarct. Oculography demonstrated (1) saccadic palsy above primary position and slow, limited vertical saccades below; (2) low-gain, restricted vertical pursuit; and (3) low-gain, abnormal phase lead, and restricted range of the vertical vestibulo-ocular reflex (VOR). Bidirectional palsy of vertical saccades is attributed to unilateral loss of burst cells in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and interruption of burst cell fibers from the opposite riMLF. Pathways mediating vertical pursuit and integration of the vertical VOR also traversed the infarct, which included the interstitial nucleus of Cajal. PMID- 3336443 TI - Effects of retinal image stabilization in acquired nystagmus due to neurologic disease. AB - We studied the effects of variable amounts of artificial retinal image stabilization (RIS) upon oscillopsia and visual acuity in eight patients with acquired nystagmus due to neurologic disease. We measured horizontal and vertical eye movements with the magnetic search coil technique and used these electronic signals to control the position of a visual stimulus on a screen in front of the patient. We also used an optical device to stabilize images of the real world upon the retina. During electronic stabilization, RIS was progressively increased until oscillopsia was abolished; this was achieved in all eight patients and corresponded to retinal image drift of 5 degrees/sec or less. In five patients with downbeat nystagmus, further increases in RIS caused the oscillopsia to reappear, but in the opposite direction. Electronic stabilization also improved visual acuity in four of five patients; the limitation of improvement could be related to coexistent visual system defects. Using electronic feedback, we could measure the range of RIS that any individual required to abolish oscillopsia; from this measurement, the components of the optical device that were best suited to provide a stable field of vision could be calculated. PMID- 3336444 TI - Carpal tunnel syndrome in Rochester, Minnesota, 1961 to 1980. AB - The incidence of carpal tunnel syndrome in the population of Rochester, Minnesota, from 1961 through 1980 was determined by use of the medical records linkage system of the Rochester Epidemiology Program Project at the Mayo Clinic; 1,016 patients (1,600 affected hands) were identified. Incidence (cases per 100,000 person-years) was 99 (crude) overall, whereas the age-adjusted rates were 52 for the men, 149 for the women, and 105 for both sexes combined. Age-adjusted incidence rates increased from 88 during the 1961 to 1965 quinquennium to 125 during the 1976 to 1980 quinquennium; these rates probably reflect better recognition rather than a true increase in incidence rates. Age-specific rates generally increased with age in men, whereas in women a peak was reached in the 45 to 54 age group. PMID- 3336445 TI - Neonatal myasthenia gravis: a new clinical and immunologic appraisal on 30 cases. AB - Anti-acetylcholine receptor (AChR) antibody titers, toxin binding blocking antibody, functional activity of serum on rat myotube cultures, IgG subclasses, and clinical data were studied in relation to the onset of neonatal myasthenia gravis (NMG) in 30 children of myasthenic mothers. Fourteen had NMG, including 4 atypical cases. Anti-AChR antibody titer was the best indication of NMG onset. NMG in a previous baby was also predictive. Pattern of IgG subclasses, presence of toxin-binding blocking antibodies, and serum functional activity were less predictive, but cast light on the mechanism of anti-AChR antibody pathogenicity. PMID- 3336447 TI - EEG outside the hairline: detection of epileptiform abnormalities. AB - We have assessed the reliability in 25 epileptic patients of EEG recording using disposable self-adhesive electrodes and a seven-channel extra-hairline montage, through comparison to simultaneous standard cable telemetry. Epileptiform abnormalities were detected in all patients on blind interpretation of data acquired using the novel technique. On comparison of specific epileptiform abnormalities identified blindly, a false positive rate of 10% and a false negative rate of 8% were encountered. Posterior temporal complexes accounted for most false negatives, and most false positives did not represent failings of the recording technique. We conclude that EEG recording outside the hairline with disposable electrodes represents a reliable means to acquire, quickly and simply, EEG evidence of epilepsy. As such, it may prove useful in the acute evaluation of patients presenting with apparent seizures. PMID- 3336446 TI - Eosinophil-induced neurotoxicity: axonal neuropathy, cerebral infarction, and dementia. AB - Although beneficial in allergic and parasitic disease, eosinophils exert nonspecific toxic effects upon host tissues, especially the central and peripheral nervous systems. Eosinophil-induced neurotoxicity is characterized by axonal neuropathy, cerebral infarction, and dementia. Eosinophil-derived cytotoxic proteins are fundamental to the pathogenesis of this disorder. PMID- 3336448 TI - Cerebral vasculitis in relapsing polychondritis. AB - Recurrent inflammation of cartilage in multiple sites is a hallmark of relapsing polychondritis (RP). Neurologic complications of this disease have begun to attract increasing attention, but the neuropathologic basis of these complications has not been described. We report a patient with RP whose autopsy showed extensive cerebral and systemic vasculitis. PMID- 3336449 TI - Asymptomatic adult Alexander's disease: entity or nosological misconception? AB - Two adults were found to have heavy deposits of Rosenthal fibers in the CNS after dying from severe systemic medical illnesses. Previously reported cases of neurologically asymptomatic adult Alexander's disease patients also had complicated systemic disease. We suggest that heavy Rosenthal fiber deposition may occur in the setting of severe medical illness and should not be classified as adult Alexander's disease. PMID- 3336450 TI - Mineralization of the basal ganglia detected by CT in Hallervorden-Spatz syndrome. AB - We studied a patient with autopsy-proven Hallervorden-Spatz syndrome (HSS) and the previously unreported finding of high-density lesions in the basal ganglia on CT. The diagnosis of HSS should be considered in a patient with dystonia and basal ganglia mineralization on CT. PMID- 3336452 TI - Negative drug trial bias. PMID- 3336451 TI - Recurrent transient monocular visual impairment caused by hyphema following intraocular surgery. PMID- 3336453 TI - MRI and dementia. PMID- 3336454 TI - PD and ciladopa. PMID- 3336455 TI - AVM surgery. PMID- 3336456 TI - Vitamin E deficiency. PMID- 3336457 TI - Familial cranial neuropathy. PMID- 3336458 TI - Phenytoin and carbamazepine. PMID- 3336459 TI - Corpus callosotomy for epilepsy. II. Neurologic and neuropsychological outcome. AB - Eighteen uncontrolled epileptic patients had neuropsychological evaluation before and after partial or total corpus callosotomy. In patients with early-onset seizures and signs of severe unilateral CNS dysfunction, callosotomy produced no deficits and several improvements. All patients whose language-dominant hemisphere did not control their dominant hand had impairments in some aspect of speech and language function after callosotomy. In some patients, unilateral deterioration of motor function was observed, and was associated with mild to moderate dysfunction in the contralateral hemisphere (ie, memory impairment or preexisting hemiparesis). Postoperative deficits occurred with partial, as well as total, section. PMID- 3336461 TI - Genetic factors in myasthenia gravis: a family study. AB - We studied forty-four patients with myasthenia gravis (MG) and their families. Thirty percent of patients had a confirmed family history of autoimmune disease; in one case this was MG. In all the families with autoimmune disease, the affected relatives were related to the patients through the maternal line. HLA-B8 and DR3 were increased in patients due to the high incidence of these antigens in female, nonthymoma patients with onset before 40 years. HLA-B5 was increased in patients with older onset. The haplotype A1-B8-DR3 was not found to be increased given the presence of B8 or DR3. PMID- 3336460 TI - Search for autonomously proliferating spinal fluid lymphocytes in patients with multiple sclerosis. AB - Recently published reports have suggested that multiple sclerosis (MS) may be associated with human retrovirus infection. Indeed, an autonomously proliferating T-cell clone was isolated from the CSF of an MS patient, an observation interpreted as indicating an infection with human T lymphotropic virus I (HTLV I). In view of these findings, we undertook a systematic search for autonomously proliferating cells in the spinal fluids of MS patients and those with other neurologic diseases (OND). In vivo activated blast cells were isolated from the CSF of six MS patients and six OND controls. A total of 442 clones were grown from these cells and assayed for their ability to proliferate independently, without the need for T cell-produced lymphokines. No autonomously proliferating clones were detected. Thus, while our data do not exclude the possibility that HTLV I transformed cells may exist in the CSF of MS patients, they do suggest that such cells are exceptional. PMID- 3336462 TI - Relationship of limbic evoked potentials to recent memory performance. AB - The relationship between limbic evoked potentials (LEPs) and memory performance was investigated in eight patients with intractable epilepsy who were candidates for temporal lobectomy. No relationship between the presence or absence of unilateral LEP and memory deficits was present. However, in both patients with bilaterally poorly developed hippocampal LEPs, verbal and visual-spatial memory tasks were impaired. In one patient with well developed LEPs bilaterally, memory function was normal. These data suggest that LEPs may assist in the evaluation of memory function during the preoperative work-up for temporal lobectomy. PMID- 3336463 TI - Neocortical morphometry, lesion counts, and choline acetyltransferase levels in the age spectrum of Alzheimer's disease. AB - We studied neocortical morphometry (cortical thickness, neurons, and glia), lesion counts (plaques and tangles), and choline acetyltransferase levels in up to 113 Alzheimer brains and 48 controls. Comparisons between young (under 65) and old (over 70) Alzheimer cases revealed more tangles in the former, but no other statistically significant differences in the measured variables. Differences in these parameters between young Alzheimer cases and young controls were similar to the differences found between old Alzheimer cases and old controls. Linear regression analyses correlating some of these variables with age in Alzheimer's disease, considered together with the effects of normal aging on the same parameters, reveal in Alzheimer's disease a spectrum of graded pathologic severity inversely proportional to age. Nevertheless, even in advanced old age (80 to 100), significant differences persist in these parameters between very elderly Alzheimer brains and controls. PMID- 3336464 TI - Alzheimer's tangles in sudanophilic leukodystrophy. AB - We present a case of infantile leukodystrophy with some sudanophilic features. A normally developed male infant did well until age 15 months. Then he had episodes of myoclonus, reversal of intellectual development, rigidity with decerebrate posturing and epilepsy, which became severe. He died at age 7 years, 10 months. On autopsy, the brain was normally developed, but there was severe demyelination and gliosis throughout the white matter; the cerebellar cortex showed atrophy. The striking, unexpected finding was the presence of numerous Alzheimer's tangles containing paired helical filaments in electronmicroscopic examination, not only in the cerebral cortex but also in the brainstem, basal ganglia, and hypothalamus including the nucleus basalis of Meynert. Other unusual findings were hyperostosis of the skull and the appearance of macrophages containing PAS positive granules in the reticuloendothelial system in many organs. PMID- 3336466 TI - State-dependent changes in the N20 component of the median nerve somatosensory evoked potential. AB - Short-latency components of median nerve somatosensory evoked potentials are generally assumed to be unaffected by sleep and level of arousal. We found that sleep prolongs the latency and alters the morphology of the N20 component in normal subjects. These changes may represent differential effects of sleep on various elements contributing to generation of the N20. Failure to control for patient state may degrade the reliability of clinical somatosensory evoked potential testing. PMID- 3336467 TI - Effect of stimulus orientation on contrast sensitivity in Parkinson's disease. AB - We studied the effect of stimulus orientation on contrast sensitivity function in 21 patients with Parkinson's disease and in 10 normal subjects. This was done by measuring contrast sensitivity over a range of spatial frequencies for vertical and horizontal sine wave grating stimuli. There was a great test-retest consistency in normal subjects and patients. Fifteen of the 21 patients showed contrast sensitivity deficit in at least one eye. Orientation-specific loss was demonstrated in 17 of the 25 "affected" eyes. The most frequent type of orientation-specific loss was a notch defect, which preferentially affected the middle spatial frequencies. We attribute orientation-specific and spatial frequency-selective loss in Parkinson's disease to a functional disruption of neurons on the visual cortex. PMID- 3336465 TI - Left-handed mirror writing following right anterior cerebral artery infarction: evidence for nonmirror transformation of motor programs by right supplementary motor area. AB - A patient with acquired, pathologic left-handed mirror writing and mirror movements during bimanual coordination is reported. CT demonstrated an ischemic infarction involving the right supplementary motor area, medial prefrontal cortex, and anterior cingulate gyrus with nearly total sparing of the corpus callosum. This case, together with recent experimental findings in monkeys, supports the hypothesis that the supplementary motor area may be responsible for nonmirror transformation of motor programs originating in the left hemisphere prior to execution by the primary motor area in the right hemisphere. PMID- 3336469 TI - Morphologic changes in the muscles of patients with postpoliomyelitis neuromuscular symptoms. AB - Thirty-five muscle biopsies were performed on 27 patients with postpoliomyelitis progressive muscular atrophy (PPMA) (8 patients had two biopsies) and 5 asymptomatic postpolio patients in an attempt to define diagnostic criteria for the newly weakening muscles and to provide insights into the mechanism of the disease. PPMA muscles that had been left weak since the original illness showed a mixture of myopathy with new and old denervation including group atrophy and nuclear clumps. Fully recovered or originally spared PPMA muscles showed signs of reinnervation and recent denervation. Perivascular or interstitial inflammatory cells (predominantly lymphocytes unrelated to phagocytosis) were noted in 40% of all the PPMA biopsies. It is concluded that (1) postpolio muscle biopsies show a spectrum of morphologic changes that depend on whether the biopsied muscle was originally affected and had fully or partially recovered, (2) the newly weakened muscles show signs of recent denervation, and (3) the presence of reinnervation in the asymptomatic muscles and the patterns of recent and old denervation in PPMA muscles provide information regarding the degree of compensation of the surviving motor neurons and their apparent failure for further reinnervation via axonal sprouting. PMID- 3336468 TI - Impaired syntactic comprehension and production in Broca's aphasia: CT lesion localization and recovery patterns. AB - Three of 50 patients with left hemisphere stroke manifested Broca's aphasia associated with deficits in syntactic processing. CT demonstrated anterior infarcts in two patients and a posterior infarct in the third. Two years later, all three patients showed improved syntactic production, but only the patient with the posterior lesion performed significantly above change on a sentence comprehension test requiring syntactic manipulations in the absence of semantic constraints. Prospective investigations combining psycholinguistic analyses and brain imaging techniques may provide empiric data relevant to neurologic models of language and ultimately may contribute to patient prognostication and rehabilitation. PMID- 3336470 TI - Gauging nursing intensity to bring costs to light. PMID- 3336471 TI - A model for success in nursing administration. PMID- 3336472 TI - Missing links in nurse practitioner education. PMID- 3336473 TI - Nursing schools: students' beacon to professionalism? PMID- 3336474 TI - Program attunes students to population-focused care. PMID- 3336475 TI - The new entrepreneurs. PMID- 3336476 TI - Personal views and insights on nursing. Mother, sister, healer, friend--nurse. PMID- 3336478 TI - Breaking through. PMID- 3336477 TI - A drug by any other name. Your guide to generic and brand names. PMID- 3336479 TI - Respiratory distress after facial trauma. PMID- 3336480 TI - L.E.A.D.: drugs for cardiac arrest (continuing education credit). PMID- 3336481 TI - Believe it or not ... peritoneal dialysis made easy. PMID- 3336482 TI - Are checklists replacing good care? PMID- 3336483 TI - Should you crush that tablet? PMID- 3336484 TI - Rx for Dr. Kent: give him control. PMID- 3336485 TI - Understanding the different types of MI. PMID- 3336486 TI - How to perform picture-perfect respiratory assessment. PMID- 3336487 TI - Managing special patients' fluids and electrolytes. PMID- 3336489 TI - Danger signs pleural friction rub. PMID- 3336488 TI - Think twice about urinary incontinence. PMID- 3336490 TI - "Why our Janet?". PMID- 3336491 TI - I'm not "impaired"--I'm an addict. PMID- 3336492 TI - Nursing shortage poll report. PMID- 3336493 TI - Assessing bowel sounds--more than just listening. PMID- 3336494 TI - When your patient is angry--what you should and shouldn't do. PMID- 3336495 TI - 6 ways to clear the air from an i.v. line. PMID- 3336497 TI - Writing a better patient care plan. PMID- 3336498 TI - Taking the scare out of caring for seizure patients (continuing education credit). PMID- 3336496 TI - Should hospital patients be screened for AIDS? PMID- 3336499 TI - Prenatal diagnosis: when reality shatters parents' dreams. PMID- 3336500 TI - What's wrong with this patient? PMID- 3336501 TI - Explaining diagnostic tests for M.S. PMID- 3336502 TI - Continent intestinal reservoir. PMID- 3336503 TI - Danger signs: rebound tenderness. PMID- 3336504 TI - Lovastatin to lower cholesterol levels. PMID- 3336505 TI - Reaching your career goals: one step at a time. PMID- 3336506 TI - Research articles: just what are they saying? PMID- 3336507 TI - Do not feed: is stopping artificial feedings ethical? PMID- 3336508 TI - Mona kept trying to set me up just to knock me down. PMID- 3336509 TI - Off-duty emergency care ... do you know your legal risks? PMID- 3336511 TI - Drug and alcohol abuse in nursing: an occupational hazard? PMID- 3336510 TI - Can your hospital sue you? PMID- 3336512 TI - Basic life support. Now's the time to update your skills (continuing education credit). PMID- 3336513 TI - Premature discharge: who's responsible? PMID- 3336514 TI - Professional nursing practice moves into the hospital admitting office. PMID- 3336515 TI - Legal implications of the impaired nurse--Part I. PMID- 3336516 TI - Standards and QA--a common sense approach. PMID- 3336517 TI - Nurses' duty to disclose. PMID- 3336518 TI - How we redefined our nursing unit. PMID- 3336519 TI - Outpatient surgical evaluations. PMID- 3336521 TI - Assumptions for success. PMID- 3336520 TI - Inauguration of a chemical dependency rehabilitation unit: supplying the nursing component. PMID- 3336522 TI - The recovering nurse: the pre-employment interview. PMID- 3336523 TI - Research: clinical integration for excellent patient care. PMID- 3336524 TI - Role expectations and role conflict of the Army head nurse. PMID- 3336526 TI - Developing the first-line nurse manager. PMID- 3336525 TI - Evaluation of adherence to policy and procedures. PMID- 3336527 TI - A head nurse's approach to multidisciplinary ethical conferences. PMID- 3336528 TI - Unofficial charting: make it work for you. PMID- 3336529 TI - Nursing economics: eight "value added" functions. PMID- 3336530 TI - The quality of caring. PMID- 3336532 TI - Is it time to convert to the modern metric system? PMID- 3336531 TI - Endocervical curettage in the evaluation of cervical disease in patients with adequate colposcopy. AB - The purpose of this study was to investigate the importance of endocervical curettage in the outpatient management of women with cervical neoplasia. From 1975-1985, 1500 patients were evaluated in our colposcopy clinic. Endocervical curettage was done routinely, even when colposcopy was adequate; 122 patients with abnormal cytology, an adequate colposcopic examination, and dysplastic epithelium in the endocervical curettings underwent conization. Of these 122 patients, 111 (91%) had cervical intraepithelial neoplasia on cone, one had microinvasion, and none had invasive cancer. In this group, there were 11 patients with abnormal cytology, normal coloposcopically directed biopsies of the ectocervix, and positive endocervical curettages. Nine of these 11 had dysplasia confirmed by conization, which would have been missed if endocervical curettage had not been performed. PMID- 3336534 TI - Peripheral neuronal changes in growth-retarded neonates: an ultrastructural study. PMID- 3336533 TI - The physician's reaction to a malpractice suit. AB - A malpractice suit can have a devastating impact on a practitioner's professional and personal life. The physician's reaction to this event is profound, affecting his own life-style and that of family, colleagues, and patients. This commentary presents an analogy between the physician's reaction to a malpractice suit and the stages of grief described by Elisabeth Kubler-Ross: the sequence of denial, anger, bargaining, depression, and acceptance. Understanding the psychodynamics of this reaction can help physicians to cope with the problems inherent in a malpractice suit and to maintain a greater stability in their personal lives. Adverse effects on medical practice and private life-style, and on the legal proceedings, can be minimized. PMID- 3336535 TI - Quantitation of proteinuria in pregnancy by the use of single voided urine samples. PMID- 3336536 TI - Decreased maternal serum magnesium concentration and adverse fetal outcome in insulin-dependent diabetic women. PMID- 3336537 TI - Effect on birth weight of erythromycin treatment of pregnant women. PMID- 3336538 TI - Ovarian remnant syndrome. PMID- 3336539 TI - Sexual functioning after treatment of in situ vulvar cancer: preliminary report. AB - Forty-two patients treated for in situ vulvar cancer at two institutions participated in structured assessment interviews and completed questionnaires to examine postoperative sexual, marital, and psychological adjustment. Patient responses were compared with a matched sample of gynecologically healthy women. The results indicated a specific pattern of sexual disruption for the women treated for preinvasive disease. Sexual behavior patterns appeared to be maintained, as was the desire phase of the sexual response cycle. However, there was specific disruption of the phases of excitement and resolution and, to a lesser extent, orgasm. In addition to a two- to threefold increase in the frequency of sexual dysfunction, 30% of the sample was sexually inactive at follow-up. Although replication of these findings is necessary, this investigation suggests that sexual functioning correlates with the magnitude of treatment. PMID- 3336540 TI - Ovulation prediction by monitoring salivary electrical resistance with the Cue Fertility Monitor. AB - The purpose of this study was to investigate the potential relationship between the salivary electrical resistance, as measured by the Cue Fertility Monitor, and the time of ovulation. Twenty-seven cycles in 18 volunteers were analyzed. A slight correlation could be demonstrated between the day of salivary electrical resistance peak and the day of luteinizing hormone (LH) peak. However, the changes in salivary electrical resistance values, arranged to the day of LH peak, were not statistically significant. The days of salivary electrical resistance peak in relation to the day of LH peak were not reproducible in individual women. The apparent relationship between the day of salivary electrical resistance peak and the day LH peak might be explained by the methodology used. It is concluded that measuring the salivary electrical resistance is of no use in predicting the day of ovulation. PMID- 3336541 TI - Prolactin stimulation tests: different response patterns after bromocriptine, lisuride, and metergoline treatment of puerperal women. AB - To elucidate different mechanisms by which bromocriptine, lisuride, and metergoline may inhibit prolactin (PRL) secretion and lactation in puerperal women, the PRL secretion patterns were examined by means of a stimulation test using an intravenous bolus of metoclopramide. After seven and 14 days of treatment, no significant difference in basal serum PRL levels was observed. However, women subjected to metergoline treatment had significantly higher responses of PRL to metoclopramide as compared with those treated with either bromocriptine or lisuride. Thus, the PRL-lowering mechanism of metergoline appears to be different from those of bromocriptine and lisuride. PMID- 3336542 TI - Secretory immune system of the female reproductive tract: I. Immunoglobulin and secretory component-containing cells. AB - We have investigated tissues from the female reproductive tract to determine whether the distribution of cells involved in the formation of secretory immunoglobulin A (IgA) molecules is analogous to that described for intestines, bronchus, and mammary and salivary glands. Fresh tissues from fallopian tube, ovary, uterus, and vagina were obtained, and sections were stained with fluorochrome-labeled polyclonal or monoclonal antibodies specific for IgG, IgA, IgA1, and IgA2 subclasses; IgM; secretory component; and J chain. Subepithelial plasma cells were identified in each specimen of fallopian tube, endocervix, ectocervix, and vagina. Approximately two-thirds of the immunoglobulin-positive cells contained IgA and J chain, indicating that they produced polymeric IgA. In comparison to tissues such as spleen and bone marrow, where IgA1-positive cells are produced, we found a high proportion of IgA2-positive cells in fallopian tube, cervix, and vagina. Epithelial cells in fallopian tube and endocervix contained secretory component. These data indicate that secretory IgA, which provides the first line of defense against invading pathogens, is produced locally in tissues of the female reproductive tract. PMID- 3336543 TI - Diagnosis of recurrent cervical carcinoma after radical hysterectomy. AB - A standard surveillance program for cervical carcinoma patients treated with radical hysterectomy is reviewed. Between 1962-1984, 249 patients with stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy were entered in the surveillance program. Of the 27 patients (11%) diagnosed with recurrent carcinoma, 17 (63%) were identified by clinical history, 22 (81%) by physical examination, five (18%) by vaginal cytology, six (22%) by chest radiography, and eight (30%) by renal contrast imaging. Combined clinical history and physical examination identified 24 patients (89%) with recurrent carcinoma. Disease recurrence was detected by vaginal cytology in one asymptomatic patient with a normal examination. The recommended surveillance procedures for patients with cervical carcinoma after radical hysterectomy include clinical history, physical examination, and vaginal cytology. Chest radiography and renal contrast imaging should be reserved for symptomatic patients. PMID- 3336544 TI - Associations between placental cadmium and zinc and age and parity in pregnant women who smoke. AB - We have previously shown that the ratio of placental zinc to placental cadmium (Zn/Cd ratio) is positively related to infant birth weight in pregnant smokers. Clinical studies have reported that older pregnant smokers are at higher risk for impaired fetal growth than younger pregnant smokers. This study examines the relationships among placental cadmium, placental zinc, placental Zn/Cd ratio, age, and parity in 98 smokers and 151 nonsmokers. Atomic absorption spectroscopy was used to analyze cadmium and zinc. Thiocyanate was used as an index of smoking status. The data were analyzed using univariate correlation and repeated-measures analysis of variance. The results showed that increased parity is related to increased levels of placental cadmium in smokers, and decreased placental zinc in smokers and nonsmokers. Age is inversely related to the Zn/Cd ratio in both smokers and nonsmokers; moreover, the oldest nonsmokers have a higher ratio than the youngest smokers. These results are consistent with a depletion of body zinc stores with increasing parity and the long half-life of cadmium in the body. The data explain in part the clinical finding that smoking during pregnancy is more harmful in older women. PMID- 3336545 TI - Relationships of vaginal Lactobacillus species, cervical Chlamydia trachomatis, and bacterial vaginosis to preterm birth. AB - The frequency of genital infection was compared among women in premature labor who delivered preterm (before 37 weeks), women in preterm labor who delivered at term, and control women who delivered at term. Both groups of women in premature labor were younger and had more previous preterm births than did control women. Women in premature labor who delivered preterm were more likely to experience rupture of membranes, intrapartum fever, and postpartum fever than were control women. The presence of bacterial vaginosis (odds ratio 2.3) and Chlamydia trachomatis (odds ratio 3.9) was positively associated, and Lactobacillus sp (odds ratio 0.2) was negatively associated, with birth before 37 weeks, using multivariable analysis to control for confounding variables. PMID- 3336547 TI - Active management of labor associated with a decrease in the cesarean section rate in nulliparas. AB - Active management of labor was introduced as the standard policy for the care of nulliparas in labor in a London maternity hospital. The basis of this management is, first, a strict diagnosis of labor and second, the early diagnosis and prompt treatment of dystocia. This study describes the outcome in 1000 consecutive nulliparas who were actively managed. In this multiracial population, active management was associated with a decrease in the cesarean section rate, without any evidence of an increase in perinatal mortality or morbidity. The results indicate that active management can be safely applied outside of Ireland to reduce the incidence of cesarean childbirth. It is suggested that this approach to the management of dystocia in labor be evaluated in the United States in a randomized controlled trial. PMID- 3336546 TI - Oxytocin augmentation of labor: a comparison of 15- and 30-minute dose increment intervals. AB - Two different regimens for oxytocin augmentation of labor were compared retrospectively in two institutions. In one regimen, the interval between dose increments was 15 minutes; in the other it was 30 minutes. All study patients were nulliparous and had uncomplicated pregnancies in spontaneous active labor; the 15-minute group consisted of 92 patients and the 30-minute group had 82 patients. No differences were demonstrated in age, dilation when oxytocin administration started, length of oxytocin administration, cesarean section rate, complications of delivery, birth weight, or Apgar scores. The maximal oxytocin dose in the 30-minute interval group was significantly lower. This group also had the oxytocin infusion stopped for evidence of uterine hyperstimulation and/or abnormal fetal heart rate tracing significantly less often (6.9% for the 30 minute interval versus 17.8% for the 15-minute interval; P = .0017). Overall, these results suggest that the longer interval does not increase the length of labor but decreases the incidence of uterine hyperstimulation. PMID- 3336548 TI - Laboratory comparison of modern vacuum extractors. AB - The Malmstrom, Soft Cup, and Mity-Vac vacuum extractors were compared in the laboratory using a tensile strength tester and a fetal cephalic model. In the test system, a linear relationship emerged between applied vacuum and maximal tractive force for all of the vacuum extractors. At their recommended working pressures, they allowed a maximum of 18-20 kg of tractive force to assist in a delivery. Calculation of the distribution of this force per unit area would appear to favor the Soft Cup. At high vacuums, all showed large amounts of tractive force and high forces per unit area. The data clearly demonstrate that high vacuum would have potentially adverse effects on the fetus and thus should be avoided. PMID- 3336549 TI - Enterococci in post-cesarean endometritis. AB - Three hundred eleven patients with post-cesarean endometritis were treated with clindamycin and gentamicin. Isolation of enterococci in the endometrium was associated with use of cephalosporin prophylaxis (P less than .001). Other risk factors for enterococcus-associated endometritis included increased numbers of vaginal examinations (P = .018) and increased length of internal monitoring (P = .006). Patients with enterococcus-associated endometritis were less likely to respond to therapy with clindamycin and gentamicin than were patients without enterococci (82.4 versus 92.7%, respectively; P = .015). Patients with enterococcus-associated endometritis also were significantly more likely to have wound infection (15.7 versus 3.2%, respectively; P = .001). In a retrospective survey of 14 patients with postpartum enterococcal bacteremias, four (29%) had a poor response to initial therapy. PMID- 3336551 TI - Maternal cigarette smoking and tubal pregnancy. AB - As part of a case-control study of tubal pregnancy, we sought to evaluate the potential etiologic role of maternal cigarette smoking. Between 1975-1979, 192 women who were treated for a tubal pregnancy in five Seattle hospitals were interviewed with regard to smoking habits and reproductive, contraceptive, and medical histories. For comparison, 459 Seattle-area women who delivered during the same period were also interviewed. Current cigarette smokers had a more than twofold increase in risk of tubal pregnancy (adjusted relative risk 2.2; 95% confidence interval 1.4-3.4) when compared with women who had never smoked. The risk for women who had stopped smoking before conception was 1.6 (95% confidence interval 1.0-2.8). There was no consistent trend between the risk of tubal pregnancy and the duration of smoking, average number of cigarettes smoked per day, age at which a woman began to smoke, pack-years of cigarettes smoked, or (among former smokers) the recency of smoking. Although several sources of bias in the present study may have created a spurious association between cigarette smoking and the occurrence of tubal pregnancy, it could well be that an increased risk of tubal pregnancy is yet another untoward consequence of cigarette smoking. PMID- 3336550 TI - Maternal hemodynamics and impaired fetal growth in pregnancy-induced hypertension. AB - Twenty-one subjects with pregnancy-induced hypertension were investigated with regard to the relationship between maternal hemodynamics and fetal growth. Five of the infants were small for gestational age (SGA) (less than tenth percentile) and 16 were appropriate for gestational age (AGA) (greater than tenth percentile). Mean arterial blood pressure, cardiac output, and stroke volume were significantly lower in the group of mothers with SGA infants than in the group with AGA infants (102 +/- 3 versus 115 +/- 3 mmHg, 5.8 +/- 0.2 versus 8.2 +/- 0.3 L/minute, and 76 +/- 7 versus 100 +/- 5 mL, respectively). The results of this investigation suggest that the hemodynamic background to the blood pressure increase in pregnancy-induced hypertension ranges from a low cardiac output, high vascular resistance condition to a high-output, low-normal resistance variant. The former subtype is often associated with the birth of an SGA infant. PMID- 3336552 TI - Spontaneous resolution of ectopic pregnancy. AB - Fourteen patients with ampullary tubal pregnancy confirmed by laparoscopy were initially managed conservatively. Serum human chorionic gonadotropin (hCG) levels were measured daily and strict clinical monitoring performed. In nine patients (64%), the tubal pregnancy spontaneously resolved. In four cases (29%), surgery was ultimately necessary. One patient with a coexistent intra- and extrauterine pregnancy was also successfully managed conservatively. There was a high probability of spontaneous resolution of the pregnancy when the serum hCG level at diagnosis was less than 1000 mIU/mL. Hysterosalpingography was performed after the spontaneous resolution of the tubal pregnancies. Tubal patency was demonstrated in all six patients, and three are currently pregnant. We conclude that conservative therapy allows spontaneous resolution of certain types of ectopic pregnancy. PMID- 3336553 TI - The effect of participation in a regular exercise program upon aerobic capacity during pregnancy. AB - This study examined the questions of whether pregnancy decreases physical fitness, as measured by maximal oxygen consumption, between the second and third trimesters, and whether maintaining a regular exercise program during the second half of pregnancy affects fitness. At the beginning of their second trimester, pregnant women were randomly assigned to either a nonexercising control group or an exercising group. They completed a maximal progressive exercise test on a cycle ergometer at 20 and 30 weeks, during which pulmonary parameters of aerobic capacity were measured. The exercising group demonstrated greater improvement in aerobic capacity than did the control group, manifested by increases in tidal volume and oxygen consumption and a stable ventilatory equivalent for oxygen. Pregnancy did not reduce maximal oxygen consumption between the second and third trimesters of pregnancy. PMID- 3336554 TI - Glycemic indices of various foods given to pregnant diabetic subjects. AB - The applicability of the glycemic index concept in pregnancy has not been established. The postprandial glucose curves were measured for nine foods (glucose, bread, raisins, dates, sweet corn, bananas, oranges, spaghetti, and green peas) in 28 gestational diabetic subjects. Uniform glycemic indices were observed for each food, similar to those reported by others in nonpregnant subjects. Postprandial glucose levels reached their peak later after glucose and bread ingestion than after the remaining seven foods. These results demonstrate that despite known changes in gastrointestinal function in pregnancy, glycemic indices are uniform after the ingestion of foods. Pregnancy does not appear to alter the glycemic indices of the foods tested. PMID- 3336556 TI - Chorionic villus sampling: experience with an initial 940 cases. AB - Of over 1000 patients referred to the Genetics & IVF Institute for chorionic villus sampling, 10% had an abnormal gestational sac at the time of initial presentation. Villus sampling could not be performed in 0.6% of cases, usually because of fibroids. Chorioamnionitis, probably related to the procedure, occurred in two patients (0.2%). The total fetal loss was 2.4%, which is not significantly different from the background fetal loss rate reported in normal pregnancies after eight weeks of gestation. The procedure-related loss was estimated as approximately 0.6%. The cytogenetic analysis routinely used was "direct" trophoblast karyotyping. There were no false-negative diagnoses. Trophoblastic mosaicism was observed in 1.3% of samples. Amniocentesis was performed in 3.5% of cases because of chorionic villus sampling failure, chorionic mosaicism, or elevated maternal serum alpha-fetoprotein (MSAFP) concentrations. Chorionic villus sampling was not associated with falsely elevated MSAFP levels at 15-18 weeks' gestation. Chorionic villus sampling has proved a safe and accurate prenatal diagnostic method associated with relatively low risk when performed by an experienced team, although additional amniocentesis will be necessary in a small percentage of pregnancies. PMID- 3336555 TI - Erythrocyte filterability in normal and high-risk pregnancy. AB - Erythrocyte filterability was studied longitudinally in normal pregnancy and in certain categories of high-risk pregnancy. Study subjects included ten normal controls, 12 insulin-dependent diabetics, eight gestational diabetics, and five essential hypertensives. Our results indicate that erythrocyte filterability remains relatively stable over the course of normal gestation. We noted no differences between controls and essential hypertensives or gestational diabetics, although a favorable effect of insulin therapy was suggested in gestational diabetics. Erythrocyte filterability and mean arterial blood pressure were not related. Insulin-dependent diabetics demonstrated a significantly elevated and widely varying erythrocyte filterability, and individual patient trends correlated well with outcome. Fibrinogen levels in diabetics rose precipitously and were significantly higher than normal throughout gestation. Fibrinogen levels paralleled changes in erythrocyte filterability, with the two parameters positively correlated. Mean glucose control had no influence on filterability. We conclude that in the diabetic pregnancy, varying erythrocyte filterability is related to altered fibrinogen metabolism and may contribute to perinatal morbidity. PMID- 3336557 TI - Presacral tumors in the female: clinical presentation, surgical management, and results. AB - A relatively infrequent and heterogeneous group of tumors with similar clinical presentation may arise in the presacral space. From 1965-1980, 70 female patients with primary presacral tumors underwent surgical management at the Mayo Clinic. Twenty-three percent had no symptoms, and their tumors were found on routine pelvic examination. Most of the symptoms resulted from compression or obstruction of adjacent organs or from pressure on pelvic nerves or bone. A palpable tumor was found in 65 (93%) of the patients. Computed tomography scan has proved valuable in determining the extent and degree of tumor invasion. The abdominal approach was selected in 39 (56%), transsacral in 20 (28%), abdominal/perineal in six (9%), and transperineal in five (7%). Complications occurred in 22 patients (31%). However, there were no operative deaths. Seventy percent of the tumors were benign, and 30% were malignant. The prognosis for patients with benign tumors was excellent and their symptoms were relieved. All 21 patients with malignant tumors died between three months and four years after surgery. Survival was not prolonged by the use of radiation or chemotherapy. PMID- 3336558 TI - A comparison of the Papanicolaou smear and the cervigram: sensitivity, specificity, and cost analysis. AB - A total of 3271 gynecology patients between the ages of 18-50 years were screened for cervical intraepithelial neoplasia and invasive cervical cancer by simultaneous Papanicolaou smears and cervigram, a noninvasive photographic method recently introduced for screening. The accuracy of each screening test, when positive or suspicious, was evaluated independently and the results compared with colposcopically directed biopsy results. The cervigram was significantly more sensitive than the Papanicolaou smear (P less than .001), whereas the Papanicolaou smear was significantly more specific than the cervigram in detecting cervical intraepithelial neoplasia (P less than .001). Cost analysis integrating sensitivity and specificity with cost per procedure indicated a greater yield of cervical intraepithelial neoplasia with the cervigram than with the Papanicolaou smear, by 3.7:1 case per dollar. PMID- 3336560 TI - Pelvic adhesions in intrauterine device users. AB - A thorough inspection of the pelvis for adhesions was made at the time of laparoscopic tubal sterilization in 2131 patients. Contraceptive use was then compared in women with adhesions (cases) and those without adhesions (controls). Current or previous intrauterine device (IUD) use was not associated with a statistically significant increased incidence of adhesions (odds ratio = 0.98, 95% confidence limits 0.58-1.64). This risk was reduced to 0.62 for current IUD users. The IUDs removed at the time of laparoscopy included the Lippes Loop, Copper 7, and the Saf-T-Coil. These findings support the use of the IUD in the appropriate patient by demonstrating no increased risk for the development of adhesions in multiparous IUD users. PMID- 3336559 TI - Significance of normal endometrial cells detected by cervical cytology. AB - A retrospective study was conducted to assess and confirm the significance of normal-appearing endometrial cells detected in cervical cytologic smears in the second half of the menstrual cycle or in the postmenopausal period. Of 440 women with normal endometrial cells identified on routine Papanicolaou smears, 179 underwent further endometrial evaluation. Endometrial disease was identified in 64 (35.7%) of those patients having endometrial sampling and/or hysterectomy within 12 months of the cytologic evaluations. These lesions included 21 cases (11.7%) of endometrial polyps, 23 cases (12.9%) of endometrial hyperplasia, and 20 cases (11.2%) of adenocarcinoma. The frequency of endometrial cancer was positively associated with age (P less than .01). Five of 20 women with endometrial cancer were asymptomatic. PMID- 3336561 TI - Use of a flexible catheter for tubal lavage in infertility surgery. AB - A flexible catheter originally designed for hysterosalpingography was used for intraoperative tubal lavage in 15 patients undergoing various infertility procedures. The catheter was easily inserted without the use of a tenaculum or cervical dilators, provided reliable dye instillation, and offered an alternative to the pediatric Foley or Buxton clamp. PMID- 3336562 TI - Incontinence history as a predictor of detrusor stability. AB - Between January 1983 and July 1985, 218 women underwent preliminary evaluation and urodynamic testing in our laboratory. Their symptoms and urodynamic diagnoses were compared to evaluate the ability of a patient's history to predict the stability of the detrusor. The symptom of stress incontinence was a sensitive detector of genuine stress incontinence (100% sensitivity) but was not very specific (65.2%). The symptoms of urgency and urge incontinence were found to have limited sensitivity (77.9%) and specificity (38.7%) in the detection of detrusor instability. Even patients with isolated complaints of stress incontinence had an incidence of detrusor instability of 34.9%, whereas 76.9% of those with a history of isolated urgency and urge incontinence had detrusor instability. Three percent of patients complaining of either type of incontinence had no objective evidence of incontinence on urodynamic investigation. The results of this study demonstrate that a patient's history is a poor predictor of the underlying cause of incontinence. PMID- 3336563 TI - Simplified sperm washing techniques and intrauterine insemination. AB - Sperm washing followed by intrauterine insemination of the husband's semen has emerged as a useful therapy. Several drawbacks restrict wider availability of this technique. The present study compared the pregnancy rate of a more complicated laboratory protocol with that of a simplified washing protocol in 42 patients. Eighteen pregnancies resulted, for an overall rate of 43%; eight occurred with the complicated protocol in 93 attempts and ten with the simplified protocol in 108 attempts, rates that do not differ significantly. We conclude that sperm washing protocols can be simplified without affecting efficacy, making the technique suitable for office settings. PMID- 3336564 TI - Is endometriosis an autoimmune disease? PMID- 3336565 TI - A comparison of labetalol plus hospitalization versus hospitalization alone in the management of preeclampsia remote from term. PMID- 3336566 TI - Efficacy of combined administration of magnesium sulfate and ritodrine in the treatment of premature labor. PMID- 3336567 TI - The effect of chorioamnionitis on the developmental outcome of preterm infants at one year. PMID- 3336568 TI - Intravasation during hysterosalpingography using oil-base contrast medium--a second look. PMID- 3336569 TI - Current therapy for dysgerminoma of the ovary. PMID- 3336570 TI - The results of microneurosurgical reconstruction in complete brachial plexus palsy. Assessing outcome and predicting results. AB - The outcome of microsurgical reconstruction in 114 adult patients presenting with complete traumatic brachial plexus palsy was analyzed. The authors examined the effects of age, time since injury, operative findings, and the techniques of reconstruction on the level of muscle recovery. Statistical and analytic computer programs were used in an attempt to determine what factors most influenced recovery. PMID- 3336571 TI - Thoracic outlet syndrome. The results of first rib resection in 100 patients. AB - We examined 100 patients with the TOS treated surgically. One hundred and twenty first ribs were resected using the transaxillary approach. Ninety per cent good and excellent results were obtained. EMGs and conduction studies through the outlet are of little value. Many of our patients presented with a double crush syndrome. Trauma was a significant antecedent in 44 per cent of our patients. The diagnosis of TOS depends on a careful clinical evaluation. There are no laboratory tests, x-rays, electrical studies, or infallible clinical tests to establish the diagnosis. There will always be some errors in diagnosis, and surgery must be advised on a basis of exclusion and with great reservation. PMID- 3336573 TI - The role of nursing practice in cancer control. PMID- 3336572 TI - Indications and results of brachial plexus surgery in obstetrical palsy. AB - This article presents the first series with long-term results of a large number of patients. As a result, it is difficult to compare these results with anything but spontaneous recovery. In most cases, the end result after surgical treatment will be better than spontaneous recovery. PMID- 3336574 TI - Legally speaking--what to do or not to do if you are sued. PMID- 3336576 TI - Gastroesophageal reflux associated with nemaline myopathy of infancy. AB - A severe infantile form of nemaline myopathy has a high mortality rate when untreated because of subsequent malnutrition and respiratory failure. Three infants with this condition demonstrated persistent vomiting, poor weight gain, and recurrent pneumonias. Esophageal manometry demonstrated decreased lower esophageal sphincter pressures and low amplitude peristalsis; 24-hour esophageal pH monitoring revealed significant gastroesophageal reflux. Medical therapy was ineffective in relieving symptoms. After antireflux surgery, vomiting and respiratory symptoms ceased, and there was no longer significant gastroesophageal reflux during pH monitoring. Our experience indicates that in some infants with nemaline myopathy a severe form of gastroesophageal reflux develops that is not responsive to medical therapy. Early surgical intervention may decrease life threatening complications associated with gastroesophageal reflux in these infants. PMID- 3336575 TI - National survey of prevalence of asthma among children in the United States, 1976 to 1980. AB - The trend in the prevalence of reported asthma was determined from data collected by the National Center for Health Statistics. The reported prevalence of ever having asthma increased among 6- to 11-year-old children between the first (1971 to 1974) and second (1976 to 1980) National Health and Nutrition Examination Surveys (4.8% to 7.6%, P less than .01). The epidemiology of asthma among children and adolescents 3 to 17 years of age in the United States was examined using data collected in the second National Health and Nutrition Examination Survey. In this paper, asthma is defined as current disease diagnosed by a physician and/or frequent trouble with wheezing during the past 12 months, not counting colds or the flu. Asthma was reported for 6.7% of youths overall and was higher in black than white children (9.4% v 6.2%, P less than .01), boys than girls (7.8% v 5.5%, P less than .01), and urban than rural areas (7.1% v 5.7%, P less than .05). Asthmatic children had a higher prevalence of other allergies (42.6% v 13.2%, P less than .01) and of allergen skin test reactivity (44.5% v 20.7%, P less than .01) than nonasthmatic children. Most asthmatics had their first asthmatic episode before their third birthday. No effect of socioeconomic status on the prevalence of asthma was noted. PMID- 3336577 TI - Bioavailability of a slow-release theophylline capsule given twice daily to preschool children with chronic asthma: comparison with liquid theophylline. AB - The reliability of slow-release theophylline products in young children has been questioned. Therefore, we studied the bioavailability of a commonly prescribed slow-release theophylline formulation (Slo-Bid Gyrocaps), administered twice daily by sprinkling the beads on applesauce. Serial measurements of serum theophylline concentrations were obtained during steady state in eight children (ages 1.6 to 5 years) after receiving a reference liquid theophylline product every six hours and also while receiving the slow-release product every 12 hours. The morning dose of slow-release theophylline was given before the child had eaten, and the evening dose was given two hours after supper. The extent of absorption of the slow-release product was 98.3 +/- 20.2% (mean +/- SD) relative to the liquid reference. The serum concentration fluctuations, expressed as percentage of the measured trough, did not differ between the two products: 108 +/- 59% v 129 +/- 97% (P greater than .05) for reference and slow-release products, respectively. Three of the eight patients had unacceptably large fluctuations (greater than 100%) while receiving the slow-release regimen, and two of these three had unacceptable fluctuations while receiving the liquid reference. The rate of absorption was slower after the evening dose of slow release product (postprandial), resulting in significantly smaller fluctuations, and lower peak concentrations. Time to peak concentration while receiving the slow-release regimen varied from two to four hours after the evening dose and from two to eight hours after the morning dose. However, the average difference between the peak concentration and the four-hour measurement after the morning dose was only 0.3 microgram/mL (range 0 to 2.6 micrograms/mL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336578 TI - Organophosphate and carbamate poisoning in infants and children. AB - The clinical and laboratory features of moderate to severe organophosphate and carbamate toxicity in 37 infants and children are presented. Ingestion of an improperly stored liquid pesticide was the most common route of intoxication (76% of patients); five (14%) children became intoxicated after playing on carpets and floors of homes that had been sprayed or fogged by unlicensed exterminators. The transfer diagnoses were incorrect for 16 or 20 patients who were transferred to our center from another institution. Miosis (73%), excessive salivation (70%), muscle weakness (68%), and lethargy (54%) were the most common abnormal signs; 49% and 22% of patients had tachycardia and seizures, respectively, and 38% of children had respiratory insufficiency that required endotracheal intubation and mechanical ventilation. The results of erythrocyte and serum cholinesterase activity assays were concordant in 83% of patients. Thirty-four (92%) patients were treated with atropine and/or pralidoxime; three patients required only supportive care. Most patients had a prompt response to therapy; however, two patients with organophosphate toxicity required multiple doses of atropine during a 24-hour period; in both instances, the doses of atropine were subtherapeutic. There were no deaths. Pneumonitis and/or atelectasis developed in ten patients, including six who had ingested a petroleum distillate-containing insecticide. PMID- 3336579 TI - Mediastinal emphysema in an adolescent with anorexia nervosa and self-induced emesis. AB - A case of asymptomatic pneumomediastinum in a 14-year-old girl with anorexia nervosa and self-induced emesis is reported to emphasize the atypical aspects of this case and the importance of differentiating benign from potentially life threatening sources of mediastinal air. Individuals who engage in purging behavior are not only at increased risk for both alveolar (primary pneumomediastinum) and esophageal perforation (Boerhaave syndrome) but may also obscure or delay the diagnosis by denying symptoms and/or previous emesis. Because esophageal perforation is serious, the presence of free mediastinal air in a patient with a known or suspected history of emesis should provoke prompt radiographic evaluation of the upper gastrointestinal tract. PMID- 3336580 TI - Vitamin K1 (phylloquinone) and vitamin K2 (menaquinone) status in newborns during the first week of life. AB - Since 1961 the Committee on Nutrition of the American Academy of Pediatrics has recommended that prophylactic vitamin K be administered parenterally to all newborn infants, although the exact requirement for vitamin K in the newborn infant is unknown. There is little information about the vitamin K1 (phylloquinone, present in green vegetables) and vitamin K2 (menaquinones, synthesized by intestinal flora) status of newborn infants. In this study during the first week of life vitamin K status was assessed by measuring serum concentrations of phylloquinone in 23 mother-infant pairs at the time of birth. Maternal phylloquinone concentration (1.7 +/- 1.0 ng/mL, mean +/- SD) was significantly higher (P less than .02) than cord serum concentration (1.1 +/- 0.6 ng/mL). All infants were then given a standard 1-mg injection of vitamin K1. Ten infants were fed formula (containing 58 ng/mL of vitamin K1) and 13 were exclusively breast-fed. On day 5 of life, serum concentrations of vitamin K1 did not differ between breast-fed (21.0 +/- 12.4 ng/mL) and formula-fed (27.5 +/- 9.7 ng/mL) infants, reflecting the large amounts of parenteral vitamin K1 at birth. During the first week of life, formula-fed infants had much higher fecal concentrations of vitamin K1 (due to large oral intake) and more significant quantities (greater than or equal to 200 pmol/g of dry weight) of fecal menaquinones (reflecting differences in bacterial flora) than did breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336581 TI - Maternal responses to the sexual abuse of their children. AB - To define categories of maternal response and determine their relationship to variable features of the abuse situation, a questionnaire was administered to mothers of 103 children returning for a routine 2- to 3-week follow-up of a sexual abuse episode. Three categories of response were identified: nonsupportive, supportive without emotional changes, and supportive with emotional changes. Nonsupportive mothers (n = 32) believed that the abuse complaint was a lie, a misunderstanding, or the child's fault. They rarely considered pressing charges or requested counseling. Supportive mothers (n = 71) believed that the child was telling the truth and that the assailant was primarily responsible. Anger, fear, anxiety, and guilt were commonly expressed. Thirty-nine of the supportive mothers reported behavior or mood changes including sleep, appetite, or somatic complaints and recurrent crying. Most were pressing charges (79%) and sought counseling for themselves (74%) and their children (82%). The 32 supportive mothers without behavior or mood changes also frequently pressed charges (88%) but sought counseling for themselves (6%) and the children (53%) less often (P less than .001). Individual personality and coping mechanisms may determine the maternal response. Maternal emotional responses do not appear to be related to variable features of the abuse situation but are significantly related to the approach to subsequent psychologic and legal issues. PMID- 3336583 TI - Parental involvement in treatment of patients with anorexia nervosa in a pediatric day-care unit. PMID- 3336582 TI - Glycoprotein filament removal from human milk fat globules by heat treatment. AB - Freeze-etch electron microscopy was applied to milk fat globules to observe surface details. A remarkable array of filaments, approximately 0.5 micron in length, was seen on human, but not bovine, globules. Heating human globules removed the filaments that were identified as high molecular weight glycoproteins by freeze-etch and gel electrophoretic analysis of the heating medium. Extraction of these globule glycoproteins was slight at 60 degrees C for one minute but substantial and tending to plateau at 80 degrees C for one minute. Such heat induced alterations of the milk fat globule surface provide an alternative or additional explanation to milk lipase inactivation as the cause of reduced milk fat absorption from heated milk by the preterm infant. PMID- 3336585 TI - American Academy of Pediatrics Committee on Bioethics: Religious exemptions from child abuse statutes. PMID- 3336584 TI - Clinical toxicology and epidemiology--a good match. PMID- 3336586 TI - Who should or can peer review subspecialty programs? PMID- 3336587 TI - A solution for the foreign body in nose problem. PMID- 3336588 TI - Call it asthma. PMID- 3336589 TI - Early discharge causes 'jaundice problem'. PMID- 3336590 TI - Discharging the jaundiced infant from the hospital: risky for the infant or physician? PMID- 3336591 TI - Screening for neuroblastoma. PMID- 3336592 TI - Lactobezoar risk. PMID- 3336593 TI - Prediction of the duration of hospitalization in patients with respiratory syncytial virus infection: use of clinical parameters. AB - To assess the possibility that clinical data available at the time of hospital admission for patients with respiratory syncytial virus infection could predict the length of hospitalization without antiviral therapy, the charts of all 102 patients admitted with laboratory documented respiratory syncytial virus infection during 1982 to 1985 were reviewed. Two thirds (65) of the patients remained hospitalized greater than three days. Prolonged hospitalization could have been predicted for 40 of the 65 patients (61.5%) based on the need for intubation and ventilation on admission (14 patients) or the presence of underlying cardiac or respiratory disease (28 patients). Of the infants hospitalized when they were less than 2 months of age, 40% required intubation and mechanical ventilation, although only 16% had underlying cardiac or respiratory disease. Mechanical ventilation was required at the time of admission or subsequently for 14% (5/36) of the 2- to 4-month-old infants with respiratory syncytial virus infection. Among the 56 patients without underlying cardiac or respiratory disease who did not require intubation at the time of admission, 25 (45%) remained hospitalized longer than three days (mean hospital stay for these 25 patients, regardless of age, was six days). Neither the respiratory rate nor the presence or absence of fever on admission was useful in predicting the likelihood of a longer hospital stay for the patients who did not require intubation. In addition, none of the initial laboratory data, including the WBC count, the percentage of band forms or polymorphonuclear leukocytes, the presence or absence of hypoxia, or the chest x-ray film findings could be correlated with a longer or shorter duration of hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336595 TI - Artificial feeding and hospitalization in the first 18 months of life. AB - The association between type of feeding and hospitalization during the first 18 months of life was examined among 1,058 infants from Jing-An district, Shanghai, People's Republic of China. Infants who had never been fed with mother's milk were categorized as artificially fed; the remainder were breast-fed. The rate of hospitalization for first episodes of respiratory infections during the first 18 months of life for the artificially fed infants was 18.0% v 11.2% for the breast fed infants (P less than .01). Multiple logistic regression analysis demonstrated that the adverse effect of artificial feeding on the hospitalization rate for respiratory infections was independent of birth weight, father's education, passive smoking, and any case(s) of chronic respiratory disease in the family. The adjusted odds ratio for the artificially fed infants compared with the breast fed infants was 2.11. The artificially fed infants were also hospitalized more frequently for gastroenteritis and other conditions, but the differences were not significant. PMID- 3336594 TI - Nutritional supplementation during two consecutive pregnancies and the interim lactation period: effect on birth weight. AB - The study consisted of 169 mothers enrolled during two consecutive pregnancies and the intervening lactation period in the Guatemalan Nutritional Supplementation Study. Women were grouped for this analysis according to the levels of caloric supplementation that they received (high or low) during two consecutive pregnancies and the period between them. The supplement also contained minerals and vitamins. Data were analyzed adjusting for maternal height, birth interval, parity, length of lactation, socioeconomic status, birth weight of the first offspring, gestational age of the second offspring, and caloric supplementation, expressed either in continuous fashion (total intake) or as caloric supplementation per week. The adjusted mean birth weights of the second offspring of women with high supplementation during two pregnancies (about an extra 180 kcal/d), and the in-between lactation period (about an extra 245 kcal/d), were up to 301 g greater than that of the low supplementation group. Women with high supplementation while breast-feeding their first offsprings and during their second pregnancies had babies up to 150 g heavier than the reference group; those mothers with high supplementation only during the second pregnancy had infants about 124 g heavier than those of the low supplementation group. Therefore, high supplementation during two consecutive pregnancies and their intervening lactation period among chronically, yet moderately, malnourished women was capable of increasing the mean birth weight to levels closer to those reported for industrialized populations. The mean birth weight increase is between two and three times greater than the effect shown in almost all of the previous studies of this topic. PMID- 3336596 TI - Meeting the health care needs of suburban youth: review of a clinical service. AB - The demographic and medical data from the first 1,000 patients registered at a suburban adolescent health service were reviewed and the findings compared with the results of an initial survey performed in the same community and other health services located in urban communities. Most of the patients were white (92%), girls (82%), and 16 to 18 years of age (63%) and had parents who graduated from high school (59%) or college (28%). They reported higher rates of participation in health-risk behaviors, including smoking (50%), drinking (60%), drug use (67%), and sexual intercourse (83%), than their peers. Seventy-two percent of the patients sought medical attention for sexuality-related or gynecologic concerns, including contraception (39%), pregnancy determination (20%), and evaluation of possible sexually transmitted disease (9%), and 28% sought attention for general medical or emotional needs, including checkups or immunizations (11%), nutritional or weight problems (4%), and emotional issues or substance abuse (4%). Management of sexuality-related issues differed from that reported in urban settings, whereas laboratory screening tests indicated that problems were similar to those in other settings. Many problems described in an initial survey of youth in the community were not seen at the adolescent health service. We conclude that a suburban-based health service may meet certain health care needs of the higher risk youth of the community but that ultimate care for adolescents remains with the private physicians in this setting. PMID- 3336598 TI - Misuse of car safety seats. AB - Correct use of car seats for small children is essential to prevent serious injuries and death from automotive accidents. Failure to use a car seat properly can contribute to serious injury or death of a child. A case study in which misuse of a car seat occurred is reported. The infant died of hemorrhage and shock secondary to liver laceration which resulted from excessive pressure over the abdomen sustained on impact. Surveys of car seat use for small children prior to and following a child restraint law are also reported. Observers noted types of car seats and specific forms of misuse. Survey results suggest that parents are more likely to misuse car seats for infants than toddlers. Medical professionals can reinforce the importance of proper car seat use by incorporating specific car seat use questions into the patient interview and by providing educational materials. PMID- 3336597 TI - Injuries to children younger than 1 year of age. AB - The circumstances and characteristics of emergency room-treated injuries in children younger than 1 year of age were studied and unintentional injuries were compared with those caused by abuse. Unintentional injuries were seen 15 times more frequently in an emergency room than injuries caused by abuse. The majority of unintentional injuries were minor, although skull fractures and fractures of the clavicle did occur. In contrast, injuries caused by abuse were commonly multiple and severe and were more likely to result in long-term disability. Results of this study indicate that unintentional injuries are rarely serious and that closed head injury, rib or lower extremity fractures, and abdominal injuries are usually indicative of abuse. PMID- 3336599 TI - Paradoxical embolism after amputation in a newly diagnosed diabetic. AB - Paradoxical embolism is rare, but it should be considered in cases of (1) postoperative arterial or cerebral embolism, (2) pulmonary embolism accompanied by systemic arterial or cerebral embolism, (3) systemic arterial or cerebral embolism in patients with a known right-to-left shunt or pulmonary arteriovenous malformation, and (4) systemic or cerebral embolism when no cardiac source can be found. Prognosis depends on both the extent of embolization and the clinical condition of the patient before and during treatment. PMID- 3336600 TI - Medical clearance for vigorous exercise. Clinical evaluation and exercise testing. AB - The practitioner plays an important role in providing guidance for exercise. Physical activity is one component of a life-style aimed at enhancing the health of the individual. When entered into with appropriate understanding and with reasonable expectations and goals, exercise can also be a major source of enjoyment. The role of the practitioner is to guide the patient to an appropriate level and intensity of exercise carried out in a suitable setting. In identifying the health habits and risk factors of the patient seeking clearance for an exercise program, physicians can do more than simply address the exercise issue. They can seize the opportunity to take a broader look at the patient's entire cardiovascular status and guide the patient into a generally beneficial program of health enhancement. PMID- 3336602 TI - Exercise for patients with chronic disease. AB - Most patients with chronic disease can benefit from rehabilitation efforts to optimize their functioning within the limitations placed on them by the disease and/or treatment and to increase their responsibility in their health care. Rehabilitation should include education and counseling in nutrition, behavioral change, exercise conditioning, and clinical concerns. The exercise portion can be accomplished in a supervised or unsupervised setting, depending on the patient's clinical status and needs. The exercise prescription must be modified to meet the clinical needs of the patient. Supervised settings may increase compliance and provide the primary care physician with valuable follow-up information that will assist in long-term medical care. The primary care physician has the responsibility of carefully screening patients, referring them into the appropriate exercise setting, and incorporating the rehabilitation results into the patient's long-term care. Physician support can dramatically enhance the success of the rehabilitation efforts. PMID- 3336603 TI - Shin splints. Diagnosis, management, prevention. AB - Our knowledge of the etiology of shin splints is incomplete. Biomechanical abnormalities are likely to be major factors in predisposing certain persons to such injury. Also, training errors are major etiologic factors. Because shin splints result from mechanical overload of various elements of the musculoskeletal system of the leg that exceed their adaptive remodeling capacity, rest and recovery should be emphasized as an important aspect of sports training. Accurate and prompt diagnosis reduces the severity and duration of the injury. Management should consist of measures to reduce inflammation and pain and to identify possible biomechanical factors that may be correctable by strengthening and flexibility exercises or by the use of an orthotic device. PMID- 3336604 TI - Drug therapy in the lactating mother. How to decide whether to prescribe or proscribe. PMID- 3336601 TI - Prescribing physical activity to prevent disease. AB - Despite an increase in the public's awareness of the ample health benefits of physical activity, less than 20% of US adults regularly participate in moderate to vigorous physical activity. For most adults, increasing physical activity even moderately is likely to benefit health. Physicians can prescribe physical activity and incorporate an emphasis on physical activity into clinical practice. PMID- 3336605 TI - Myasthenia gravis. A well-understood neuromuscular disorder. AB - Myasthenia gravis is a disorder of neuromuscular function caused by autoimmunity to acetylcholine receptors and the postsynaptic region of the neuromuscular junction. Clinically, it is manifest by abnormal weakness and fatigability of skeletal muscle. Distribution and severity of weakness vary among patients. Most cases can be treated effectively with a combination of anticholinesterase inhibitors and glucocorticoids. Thymectomy is often recommended. PMID- 3336606 TI - 'Right' or 'privilege' to medical care? PMID- 3336607 TI - Arsenic poisoning. Ongoing diagnostic and social problem. AB - Arsenic, commonly found in insecticides, herbicides, and industrial materials, is involved in the majority of heavy metal poisonings reported in the United States. Accidental poisoning appears to be most common in the pediatric age-group, whereas intentional and covert poisonings predominate in adults. Diagnosis is often difficult. The clinical presentations of arsenic poisoning, both acute and chronic types, represent a wide spectrum, largely dependent on route of exposure, chemical form, and dose. Because the patient or others providing the history may suppress information on exposure and because toxic levels of arsenic in the system drop rapidly in the first 24 hours, swift administration of diagnostic tests is important. Physician follow-up is determined by the route of exposure to arsenic and may involve referral to a social service network or a mental health facility. PMID- 3336608 TI - Goal setting. A method to help patients escape the negative effects of stress. PMID- 3336609 TI - Buerger's disease in a middle-aged woman. A unique presentation. AB - We have presented the 11th probable case of Buerger's disease in a female patient. She had the oldest age of onset of any female patient with this disease yet described. In addition, she was the first female patient who was not actively smoking at the onset of ischemic symptoms. Hence, Buerger's disease should be included in differential diagnosis in any female patient, young or middle-aged, who is an active or former cigarette smoker, has a history of Raynaud's phenomenon, and presents with ischemic disease of the distal extremities. Poor results from attempted revascularization surgery can be anticipated. PMID- 3336610 TI - How to help patients stop smoking. A practice-based program for 'kicking the habit'. PMID- 3336612 TI - Psychiatric disorders in the elderly. Psychopharmacologic management. AB - Psychiatric management of elderly patients is a challenging task because of the many age-related physiologic changes and medical problems in this population. Thorough patient evaluation is essential to rule out somatic disorders and determine underlying causes. Somatic complaints must be taken seriously, even if a patient is receiving treatment for a psychiatric disorder. Psychotropic therapy is used mainly for controlling depression, agitation, and psychotic symptoms. If psychiatric symptoms persist or become worse, psychotropics should be discontinued to prevent possible drug toxicity (eg, anticholinergic delirium) and psychiatric consultation should be requested. PMID- 3336611 TI - Pressure sores in the elderly. A systematic approach to management. AB - Pressure sores are a serious but often avoidable problem. The best management plan focuses on early identification of high-risk patients, appropriate allocation of resources, and adequate techniques of pressure relief. A standardized treatment plan that is familiar to care givers should be followed. The clinician must correct all conditions that retard the healing process, including nutritional deficits and underlying medical problems. Multiple-drug therapy must be eliminated, and only established skin care protocols should be followed. Use of systemic antibiotics is reserved for complications, such as osteomyelitis, cellulitis, and sepsis. PMID- 3336613 TI - Treatment of insect stings. PMID- 3336614 TI - Smoke inhalation injury. PMID- 3336616 TI - Communication between physicians and physical therapists. AB - The purposes of this study were 1) to identify therapists' and physicians' attitudes and opinions about the physician-physical therapist communication dyad, 2) to identify potential areas for improvement in this communication process, and 3) to provide physical therapists and physical therapy students with basic guidelines for optimal communications. Ten physical therapists and 8 physicians participated in individual interviews that were taped and subsequently transcribed. The transcriptions were compiled and analyzed by an interpersonal communication expert (B.W.B.) for trends and themes. Findings of the study include 1) physical therapists want increased accessibility to and communication with physicians and 2) physicians want brief communication with clear objective data provided by the therapists. Basic guidelines developed for physical therapy students as a result of this study include 1) identify physicians with whom you can communicate most easily, 2) learn your physicians' schedules, 3) organize beforehand so that communication is clear and concise, 4) be polite but self assured, 5) ask your supervisor or other staff therapists for advice, and 6) use the telephone discriminately. This study emphasizes that communication with physicians must be approached on an individual basis. Each physician differs in personality, philosophy of patient care, and expectations of physical therapy. Therapists should take the initiative in developing good rapport and maintaining a viable relationship with physicians. PMID- 3336615 TI - Effects of two gravity inversion methods on heart rate, systolic brachial pressure, and ophthalmic artery pressure. AB - The purpose of this study was to investigate the effects of two static gravity inversion methods with either ankle or thigh suspension on heart rate (HR), systolic brachial pressure (SBP), and ophthalmic artery pressure (OAP). Twenty healthy subjects were assigned randomly to one of two treatment groups of 10 subjects each. Each group completed a 25-minute protocol with two 5-minute inversion periods. The research attempted to control for treatment anxiety and for the effects of ocular plethysmography (the procedure used to measure OAP). A 2 X 2 multivariate analysis of variance for repeated measures was used to analyze the differences of cardiovascular change between the two inversion methods. The hypothesis that the subjects' HRs, SBPs, and OAPs would not differ between ankle and thigh suspension methods for five minutes of inversion was not rejected. Leg position did not affect the HR or arterial responses during full static inversion. Gravity inversion produced no significant changes in HR and SBP between 2.5 and 5 minutes of inversion. Arterial pressures measured at 5 minutes of static inversion did not differ from arterial pressures measured between 2.5 and 5 minutes, but because of increases in OAP during inversion, ocular safeguards are recommended for subjects during inversion. PMID- 3336617 TI - Development of prone extension postures in healthy infants. AB - The purposes of this study were to 1) investigate the sequence of development of head, upper extremity, and lower extremity extension in the prone extension posture in healthy infants; 2) identify the variations in the sequence; and 3) compare these postures within the sequence with the development of prone-on elbows and prone-on-hands postures. Twenty healthy, full-term infants were observed longitudinally from 8 to 28 weeks of age. Two of the infants could not complete the study, and two infants never used the prone extension posture. The data from 16 of the infants, therefore, were analyzed. The results indicate that the sequence of development of the prone extension posture consists of head extension, followed by lower extremity extension, and then upper extremity extension. The results also indicate that upper extremity extension in the prone extension posture does not appear to be a prerequisite for the prone-on-elbows or prone-on-hands postures. These findings suggest that infants may use different strategies for developing motor control in the head and lower extremities than in the upper extremities. This information adds to our knowledge of the normal developmental process and may have significance in the planning of physical therapy programs. PMID- 3336618 TI - Effect of arm ergometry training on wheelchair propulsion endurance of individuals with quadriplegia. AB - Arm cycle ergometry has been shown to be an effective mode of cardiopulmonary training for individuals with spinal cord injuries. Arm cycle ergometry training results in an increased maximal oxygen uptake, exercise-induced bradycardia, and increased physical work capacity. Whether improvements in cardiopulmonary function parallel improvements in functional endurance, however, is unknown. In addition, no readily available tool to evaluate improvements in functional endurance has been identified. The purpose of this investigation was to determine the effects of arm cycle ergometry training on the wheelchair propulsion endurance of individuals with spinal cord injuries. Eight adult men with quadriplegia were evaluated before and after eight weeks of arm cycle ergometry training. A modified Cooper's 12-minute run-walk test, a sustained wheelchair propulsion task, was used to document improvements in functional endurance. Submaximal exercise heart rate, physical work capacity, and maximal oxygen uptake were used to document improvements in cardiopulmonary function. The results demonstrate that improvements in cardiopulmonary function parallel increases in wheelchair propulsion endurance. A sustained 12-minute wheelchair propulsion task is shown to be a readily available tool in the evaluation of functional endurance of individuals with spinal cord injuries. The improvements in wheelchair propulsion endurance should assist the individual in completing activities of school, work, recreation, and daily living. PMID- 3336619 TI - String wrapping versus massage for reducing digital volume. AB - The purposes of this study were 1) to compare the relative effectiveness of two common methods of treating hand edema, retrograde massage and string wrapping, and 2) to compare these two methods with two techniques of combining them. Fifty six digits of the hands of 14 subjects were studied. Because all of the subjects demonstrated generalized hand edema, comparisons of different digits of the same subject could be made on each visit. Effectiveness rankings of the treatment methods were made after each visit. A clear pattern of effectiveness emerged that suggested that superimposing massage on an already-wrapped digit was more effective than either massage or string wrapping alone. Average circumferential reductions of digits further supported the hypothesis that a combination of string wrapping and massage would be more effective than the individual string wrapping or massage techniques. No significant difference in effectiveness was found between massage and string wrapping when used singularly. PMID- 3336620 TI - Spinal effects of head-down tilting. Part 1--Low back contour changes. AB - The purpose of this study was to compare the effects of two methods of inversion therapy and four common exercise positions on the shape of the low back. We studied 25 healthy subjects in six exercise positions: 1) inverted with lower limbs extended (ILLE), 2) standing, 3) supine, 4) inverted with lower limbs flexed (ILLF), 5) sitting, and 6) hooklying. A manual measurement system was used to determine low back contours (LBCs) from S2 upward for 19 cm at 1-cm intervals. Contour data were reduced to mean contour values (MCVs). Results showed that the standing and sitting positions produced the largest and smallest MCVs, respectively (p less than .01). The ILLF MCV was smaller (p less than .05) than both supine MCVs but not appreciably different from the ILLE MCV. The ILLE and ILLF positions significantly reduced (p less than .01) MCVs compared with the standing position. Neither position decreased the MCV as much as the sitting position. These results support the use of inversion therapy to reduce the depth of the LBC when sitting is inappropriate. PMID- 3336621 TI - Modification of sitting posture of patients with hemiplegia using seat boards and backboards. AB - The purpose of this study was to evaluate and compare the effects of using seat boards only and a combination of seat boards and backboards on wheelchair posture. Forty-one patients with hemiplegia secondary to cerebrovascular accidents were assigned sequentially to 1) a group that used seat boards only (SB Group), 2) a group that used both seat boards and backboards (SBB Group), or 3) a group that used no boards (Control Group). The SB and SBB Groups used the boards throughout rehabilitation. Wheelchair sitting posture was measured at entry to and discharge from the rehabilitation program. The SB and SBB Groups were measured with and without boards. Anterior-posterior pelvic tilt, lumbar lordosis, thoracic kyphosis, lateral flexion, and lateral pelvic tilt were measured using a gravity goniometer, photographs, and calipers. Use of seat boards was associated with a decreased lateral pelvic tilt of 2.3 degrees at discharge while the seat boards were in place. The use of seat boards and backboards combined was associated with decreased lateral pelvic tilt of 3.1 and 1.6 degrees, increased anterior pelvic tilt of 13.1 and 11.1 degrees, and decreased thoracic kyphosis of 13.0 and 14.2 degrees at entry to and at discharge from the rehabilitation program, respectively, while the boards were in place. At the end of rehabilitation when the boards were removed, no long-term postural changes had occurred in the treatment groups compared with the Control Group. This study demonstrated that seat boards and backboards in wheelchairs improve certain postural deviations of patients with hemiplegia, but that these improvements are not maintained when the boards are removed after 5 to 10 weeks of use. PMID- 3336622 TI - Precasting work sheet--an assessment tool. A clinical report. AB - Physical therapists often use casting as an adjunct to traditional management of patients with brain injury. Casts generally are used on these patients for one of two reasons: 1) to increase range of motion with the use of serial casting or 2) to augment functional treatment with the use of inhibitive casting. This clinical report describes serial and inhibitive casts and introduces a precasting work sheet that promotes the selection of appropriate casting patients and necessary planning. The work sheet guides the therapist through an assessment of patient data relevant to casting, including passive range of motion, postural tone and abnormal reflexes, and voluntary movement. The precasting work sheet helps therapists gain expertise in casting by familiarizing them with the factors to consider before casting, encouraging them to set goals for casting, and helping them to determine whether the goals were met. PMID- 3336623 TI - Dynamic splinting after extensor hallucis longus tendon repair. A case report. AB - Surgery often is recommended to prevent the symptomatic hallux flexus and equinus deformity that may result from traumatic laceration of the extensor hallucis longus (EHL) tendon. Surgical repair of the EHL tendon, however, may cause scarring and adhesion formation that results in a loss of EHL tendon function. Dynamic splinting may be used during rehabilitation to prevent these complications. The purpose of this case report is to describe the use of dynamic splinting in the treatment of a patient after EHL tendon laceration and surgical repair. PMID- 3336624 TI - Career profile of and feedback from graduates of a midwest curriculum. AB - The purpose of this survey study was to create a career-activity profile of all physical therapy graduates from the University of Nebraska Medical Center (1972 1985) and to gather evaluative information for the planning of a postbaccalaureate entry-level degree program for physical therapy. A majority of the survey respondents (91%) were employed in physical therapy when the survey was made and were satisfied with their undergraduate program. A majority of the respondents resided in Nebraska or surrounding states and identified similar changes within the physical therapy profession. The results supported the hypothesis that a negative correlation would exist between the salaries of full time physical therapists and the size of the population they serve. Graduates' recommendations to increase clinical education and student exposure to specialties were included in the University of Nebraska's postbaccalaureate physical therapy degree proposal. This graduate feedback system was helpful with physical therapy program planning to meet the identified needs of this regional area. PMID- 3336625 TI - Nuclear magnetic resonance spectroscopy of skin: predictive correlates for clinical application. AB - The first application of phosphorous 31 (31P) and proton (1H) nuclear magnetic resonance (NMR) spectroscopy to the analysis of the metabolic profiles of skin flaps in a rat model and of human skin grafts is presented. Resonances of adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) were identified in 31P nuclear magnetic resonance spectra. Resonances of phosphocreatine, creatine (Cr), and lactate (Lac) were identified in 1H nuclear magnetic resonance spectra. The most significant finding was the substantial presence of phosphocreatine as the major high-energy phosphometabolite in mammalian skin, a finding which heretofore has not been widely recognized. An energy shuttle between phosphocreatine and ATP is operative in skin to buffer the fall in ATP during ischemic (anaerobic) insult. Inability to replenish exhausted phosphocreatine reserves predictively correlates with eventual flap necrosis. We have defined and analyzed temporal fluxes in the phosphocreatine-creatine and phosphocreatine plus creatine-lactate ratios by proton nuclear magnetic resonance. Both are sensitive, accurate, and unambiguous early prognostic indices of eventual flap outcome. These findings support the concept that the fate of a flap may be established as early as 3 hours after elevation and have laid the groundwork for development and application of noninvasive in vivo nuclear magnetic resonance spectroscopy to the study of skin flaps in animals and humans. PMID- 3336626 TI - A simple instrument for surgical tattooing and skin marking. AB - We describe here a reliable and inexpensive surgical marking instrument utilizing materials that are readily available. It can be used preoperatively or intraoperatively for tattooing points of reference in spite of vigorous preps. PMID- 3336627 TI - The "jam roll" flap for fingertip reconstruction. AB - A method of fingertip reconstruction using a deepithelialized cross-finger flap in "jam roll" fashion is described. The technique has found relatively frequent indications. PMID- 3336629 TI - Nasal reconstruction with the expanded forehead flap. AB - This report details the experience with nine patients over a 3-year period who had partial or total nasal reconstruction using an expanded forehead flap. The history of nasal reconstruction is reviewed, emphasizing the evolution of the forehead flap as the ideal donor site. The author's experience with skin expansion of the forehead to produce a thin ideal flap is presented in detail. Complications of the procedure are reviewed. Technical considerations to achieve a good result are emphasized. The forehead donor site is minimal and well accepted. This procedure provides a solution to a major problem with partial and total nasal reconstruction. PMID- 3336628 TI - Various uses of the septum in rhinoplasty. AB - The nasal septum can be used with impunity to assist in cosmetic and reconstructive rhinoplasty if an L-shaped bridge with anterior prow is preserved or constructed to maintain normal support to the nose. The septum can serve, of course, as a reservoir of cartilage grafts. Under special conditions, it can spare mucosal and chondromucosal or even osteochondromucosal flaps to aid in the supply of lining and support in reconstructions. The L-shaped septal chondromucosal flap has been found of value in total distal reconstructions and is now offered as a possible adjunct in the correction of certain intact but congenitally flat and/or short noses. PMID- 3336630 TI - Cartilage crusher. PMID- 3336631 TI - The -ize have it. PMID- 3336632 TI - Reverse-flow island flap: clinical report and venous drainage. PMID- 3336633 TI - Antibiotics in the tissue expander to decrease the rate of infection. PMID- 3336634 TI - Island gluteus maximus myocutaneous flap. PMID- 3336635 TI - Refinement of the radial forearm flap donor site using skin expansion. AB - The radial forearm flap has proven to be versatile for free vascularized composite tissue transfers as well as for ipsilateral upper extremity reconstructions that require no microsurgical expertise. The most common objection to this otherwise advantageous donor area has been the subsequent nonaesthetic donor-site deformity. In addition, skin grafts frequently fail over the flexor carpi radialis tendon leading to chronic skin breakdown or at best tendon adhesions. Both these concerns may be ameliorated by means of tissue expansion of the remaining dorsal forearm skin to then allow removal of the skin grafted portion of the donor site. These problems should be anticipated at the time of initial flap elevation so that the same incisions can be used for immediate placement of expanders. PMID- 3336636 TI - Tissue expander injection dome leakage. AB - Injection dome leakage was found to be the cause for partial disappearance of the saline solution injected into some tissue expanders. When the injection domes of 22 consecutively removed tissue expanders were checked, we found that the average leakage pressure of these was 32 mmHg, with a range of 8 to 110 mmHg. When the patients were lying on their expanders, the weight of the corresponding body part caused intraluminal pressures of up to 90 mmHg in their expanders. Following removal of the expanders, the total leakage was calculated quantitatively and found to be maximally over 50 percent of the injected volume in some instances. The leakage flow through the injection dome in seven consecutively removed expanders was checked at pressures of 25, 50, and 75 mmHg over 30 minutes and was found to be slow. The possibility of injection dome leakage should be kept in mind, however, as a potential complication under unfavorable conditions. At the same time, we want to emphasize that in most instances tissue expanders function quite well and in predictable ways. PMID- 3336637 TI - Survival of island flaps after tissue expansion: a pig model. AB - Survival of island flaps after tissue expansion has been studied. Expanders were placed under each buttock flap of six minipigs and one side was expanded while the other was left empty as a control. Both flaps were then raised and isolated on their vascular pedicles in order to compare flap survival 7 days later. It was found that the survival lengths of the expanded flaps were approximately 50 percent greater than those of the delayed controls. Microangiography suggested that the diameter of the axial artery increased following expansion. In clinical practice this technique would provide a larger flap for reconstruction and the possibility of direct closure of the donor site. In addition, the observed increase in vessel caliber should facilitate the free tissue transfer of expanded flaps. PMID- 3336638 TI - The fate of sternotomy scars in children. AB - The scars from sternal split incisions were examined and rated in 101 consecutive children attending a cardiology clinic at least 1 year after surgery. Each scar was rated as excellent, good, acceptable, or poor. Factors that may correlate with scar quality were analyzed. This analysis showed that poor scars were most likely to have been closed with intracuticular polyglycolic acid suture; males were more likely to have better scars than females; the younger the child at operation, the better was the scar result; and only 18 of the 69 scars that were hypertrophic 1 year postoperatively remained so after a mean of 5.5 years. PMID- 3336639 TI - A comparison of intramarginal and extramarginal excision of hypertrophic burn scars. AB - Hypertrophic scarring is common in burn patients. The treatment of such scarring is difficult, and recurrence of the hypertrophic changes after scar revision is not uncommon. It has been suggested that intramarginal excision diminishes the chances of recurrent hypertrophic scarring, but we could not find any papers in the literature actually comparing intramarginal and extramarginal excisions. We therefore reviewed our experience with intramarginal and extramarginal excision of hypertrophic scars. Between October 30, 1979, and March 26, 1986, we excised 50 hypertrophic scars in 23 burn patients. Thirty-one (62 percent) of the excisions were intramarginal and 19 (38 percent) were extramarginal. We compared the results and observed that the intramarginal excisions yielded better results than the extramarginal excisions. PMID- 3336640 TI - Rheumatoid arthritis and Dupuytren's contracture. AB - Of four patients with rheumatoid arthritis and Dupuytren's contracture, two were not aware of the presence of Dupuytren's contracture. When both diseases coexist, the presence of rheumatoid hand deformities, especially flexion and ulnar deviation of the metacarpophalangeal joints, may mask the flexion deformity caused by Dupuytren's contracture. Careful clinical examination should rule out the presence of a pathologic fascial cord. When reconstructive surgery is indicated for the rheumatoid hand in the presence of advanced Dupuytren's contracture, staged surgery would be appropriate and reconstruction of Dupuytren's contracture should precede other surgery. PMID- 3336641 TI - Roping injuries in the hand: mechanism of injury and functional results. AB - Twenty-two patients with roping injuries to 38 digits, including 19 patients injured while team roping, are discussed. Ten digits in nine patients were successfully revascularized or replanted. Seven digits in three patients failed after initial success. One patient is included in both categories. The failure rate is 41 percent for all 17 digits. Average follow-up is 18 months. The dominant hand was injured in 83 percent of team roping injuries; the thumb is the most commonly injured digit. Average interphalangeal motion for thumb replants is zero; for revascularizations, it is 47 degrees. There was 43 percent return of pinch strength for thumb replants compared to 83 percent return for a single thumb revascularization. The most common mechanism of injury was catching the roping thumb in the "thumb up" position during dallying. There are good motion and pinch strength with thumb revascularizations provided tendons and the interphalangeal joint are intact. Reconstruction of the flexor pollicis longus in the replanted thumb gave poor results. Primary tenodesis or arthrodesis is recommended. PMID- 3336642 TI - Can stitches get wet? AB - This study was performed to answer the question of whether or not a patient can wet stitches after a minor soft-tissue surgical procedure without increasing the incidence of infection or disruption of the wound. One hundred consecutive patients underwent an excision of a skin or soft-tissue lesion closed either primarily or with a local flap. Monofilament nylon was used. There were 55 benign lesions and 45 malignant lesions. All procedures were performed using local anesthesia on an ambulatory basis. All patients were asked to wash the wounds with soap and water twice a day starting the morning after surgery. All wounds healed without any infections and without any disruption or dehiscence of the wounds. PMID- 3336643 TI - The plastic hand surgeon: an endangered species? PMID- 3336644 TI - Eyelid reconstruction in pachydermoperiostosis. AB - Our experience with an unusual case of pachydermoperiostosis is described. This case was accompanied by enlargement of the eyelids, excessive secretions, and difficulty in opening the eyes. Partial and serial excisions of the upper and lower eyelids were done to correct the thickened eyelids. As a result of the operations, this patient can open his eyes fully and the secretions have decreased. PMID- 3336645 TI - Extended application of the biceps femoris musculocutaneous flap. AB - Since its description in 1977, the use of the biceps femoris musculocutaneous flap has been largely limited to reconstructions around the hip and perineum in paraplegic patients. The safety with which this flap can be transposed has been questioned owing to the segmental nature of its blood supply. Cadaver dissections in 10 fresh lower limbs showed that anterolateral transposition could be achieved without the need to sacrifice any of the major vascular pedicles (numbering two to three) which penetrate the long head of the muscle within 10 to 14 cm of the ischial tuberosity. We report on the use of this flap to resurface the anterolateral aspect of the lower thigh and restore stability and extension to the knee joint following extensive damage to the quadriceps mechanism. PMID- 3336646 TI - Direct monitoring of microvascular anastomoses with the 20-MHz ultrasonic Doppler probe: an experimental and clinical study. AB - The 20-MHz ultrasonic Doppler probe was used to determine its efficacy as a continuous monitoring technique for microvascular anastomoses. A 1-mm2 piezoelectric crystal embedded in a soft silicone sleeve was sutured directly to the blood vessel distal to the anastomosis. Using the dog femoral artery, simultaneous measurement of velocity and blood flow with an electromagnetic flowmeter established a direct correlation between flow and velocity with a 14 percent error at maximum flow and an 18 percent error at minimum flow conditions. The probe was then implanted in the rabbit femoral artery for 1 week (n = 3) and 4 weeks (N = 6), demonstrating that a continuous tracing could be obtained without injury to the vessel. Our clinical study included 63 patients undergoing free-tissue transfers monitored with the implantable probe for 7 to 29 days (average 10.5 days). Twenty-three flaps were buried. Two patients experienced loss of arterial tracing due to malfunction of the probe (3 percent). Three patients had a venous thrombosis with a present arterial tracing. There were no flap failures per se. All probes were removed without mishap, and there were no complications related to the probe. We conclude that the 20-MHz ultrasonic Doppler probe holds promise as a useful monitoring method. PMID- 3336647 TI - Experimental evaluation of the antibiotic carrying capacity of a muscle flap into a fibrotic cavity. AB - A study was undertaken to determine the antibiotic carrying capacity of a transferred muscle flap into a fibrotic cavity using a tissue cage model in rabbits. Blood and chamber fluid antibiotic levels were determined after intramuscular hindlimb gentamicin injection up to 56 days following muscle transfer. This study suggests that muscle flaps increase the concentration of antibiotics that can be achieved within a fibrotic cavity. The measurable peak level decreases with time, probably due to increased scarring around the muscle. This model should enable the study of many different classes of antibiotics with different protein binding and other administration schedules using multiple timed doses or a combination of agents. PMID- 3336648 TI - Lip-nasal aesthetics following Le Fort I osteotomy. AB - Forty-one patients undergoing Le Fort I osteotomy for superior and/or anterior repositioning of the maxilla were prospectively studied for changes in soft tissue morphology of the nasomaxillary region. Nasal parameters studied were changes in interalar rim width and nasal tip projection. It was observed that alar rim width increases with anterior and/or superior repositioning of the maxilla, but increases in nasal tip projection occur only when there is an anterior vector of maxillary movement. These nasal changes could not be quantitatively correlated to magnitude of maxillary movement. Lip changes studied were the horizontal displacement at the vermilion border and subnasale versus that of the incisal edge and point A, respectively, when the maxilla is sagittally advanced and the vertical shortening of the lip versus that of the incisal edge when the maxilla is shortened. Using linear regression analysis, horizontal displacement of the upper lip at the vermilion border was 0.82 +/- 0.13 mm for every 1 mm of maxillary advancement at the incisal edge (p less than 0.001) and 0.51 +/- 0.13 at the subnasale for every 1 mm of maxillary advancement at point A (p less than 0.001). Eighty percent of patients undergoing maxillary intrusive procedures had lip shortening ranging from 20 to 50 percent of the vertical maxillary reduction. Surprisingly, no statistically significant correlation could be demonstrated for lip shortening versus extent of vertical maxillary reduction. Previous literature in disagreement with these findings is discussed. Guidelines for treatment planning utilizing these data are suggested. PMID- 3336649 TI - Anatomic surgical dissection of the extraparotid portion of the facial nerve. AB - The direction followed by the facial nerve branches beyond their emergence from the ventral, cephalic, and caudal borders of the parotid gland up to the facial muscles has been studied by several anatomists, but no consistent description of them has been given so far. This research, based on the dissection of 30 hemifaces, studies the characteristics of those branches using three points of reference: the intertragal notch, the palpebral lateral commissure, and the labial commissure. Tables showing average length and number of branches have been computed with a statistical level of confidence of 99 percent. No fixed common pattern suitable to represent the distribution of branches of the facial nerve in a model was found, but as a rule, these branches run beneath the superficial musculoaponeurotic system (SMAS) in their path below the zygomatic arch, and approximate emergence points have been identified. In the opinion of the authors, such points may be of more surgical relevance than a theoretical pattern of arborization. PMID- 3336650 TI - Mammary implants, diving, and altitude exposure. AB - Mammary implants were exposed to various simulated dive profiles followed by altitude exposures to stimulate aircraft travel and then were observed for bubble formation and volume changes. Minimal volume changes occurred after each dive. Numerous bubbles formed, however, reaching their maximum size in 3 hours. By comparison, when implants were exposed to high altitude following a dive exposure, significant volume changes occurred. This in vitro study showed that bubble formation and volume expansion occur after exposing implants to diving and altitude, but the circumstances required to produce these changes in vivo are extremely unlikely to occur normally. PMID- 3336651 TI - Accelerated tissue expansion with the "overfilling" technique. AB - Temporary overexpansion of the tissues at each filling session increased the actual inflation volume by about 59 percent. This shortened the process of tissue expansion considerably. "Overexpansion" means that the pressure in the expander is increased to a point where the dermal capillary flow is zero or the patient experiences so much discomfort that inflation cannot be carried out any further. The pressure in the expander is thereafter gradually decreased by taking out saline until both the capillary refill and all other clinical criteria are sufficient for safe dermal circulation. Comparison of the expander volume at the final pressure to the initial filling volume at the same pressure before the "overfilling" confirmed an average gain of about 59 percent in 14 patients. PMID- 3336652 TI - Soft-tissue expansion in the lower extremities. AB - Soft-tissue expansion enjoys ever-wider use, but to date an experience using this technique in the lower extremity has never been presented. We reviewed our first 16 patients to describe the indications and contraindications for the use of tissue expansion in the lower extremity. Guidelines evolved from study of the data. Soft-tissue expansion merits consideration for coverage of problem wounds, in preparation for removal of large benign lesions, and for the repair of contour defects. The operator should know that an open wound below the knee predicts a complication if soft-tissue expansion is attempted in that location. In the thigh, incisions can be confidently placed at the edge of the defect. In every location, large expanders should be chosen so that they are as long as or longer than the adjacent defect. The increase in circumference of the limb should be followed. Simple designs for advancement flaps usually work well. As our experience has grown, reconstruction using soft-tissue expansion in the lower extremity has become safer and the results more predictable through better patient selection and diligent monitoring of intraluminal pressures, even if only by ensuring that the patient is always comfortable. Soft-tissue expansion has a role in reconstruction of the lower extremity. PMID- 3336653 TI - The V-Y plantar flap for reconstruction of the forefoot. AB - Stable reconstruction of the forefoot remains a formidable challenge. The present study reviews our experience with a flap of plantar skin and fascia advanced in a V-Y manner to cover metatarsal head ulcers. Although this technique was used in a variety of clinical situations, 71 percent of the 38 patients were diabetic with neurotrophic wounds. The anatomic basis for flap design is reported based on 10 fresh cadaver dissections. Flap survival was 100 percent. Ulcer recurrence was related to the problems inherent in the hypesthetic foot. We feel that judicious manipulation of the bony architecture along with weight-dispersion shoe inserts assists in preventing recurrent ulceration. PMID- 3336654 TI - The diagnosis of osteomyelitis in patients with pressure sores. AB - A prospective blind trial was undertaken to assess the usefulness of commonly used tests to diagnose osteomyelitis underlying pressure sores. Sixty-one pressure sores were studied, with a histopathologic diagnosis from the ostectomy specimen being available in 52. White cell count, erythrocyte sedimentation rate, plain pelvic x-ray, technetium-99m bone scan, computerized tomography, and Jamshidi needle bone biopsy were studied. The most useful individual test was a needle bone biopsy, with a sensitivity of 73 percent and a specificity of 96 percent. Technetium-99m bone scans and computerized tomography are not indicated in the diagnosis of osteomyelitis associated with pressure sores. Plain pelvic x ray, white cell count, and erythrocyte sedimentation rate, with a diagnosis of osteomyelitis if any test is positive, is the most sensitive (89 percent), specific (88 percent), noninvasive workup. Jamshidi needle biopsy may be useful where these tests are negative and a clinical suspicion of osteomyelitis remains. Extent of surgical debridement and antibiotic therapy can then be rationally decided on the basis of this information. PMID- 3336656 TI - The thigh flap: an osteomyocutaneous free-flap model in the rat. AB - A new experimental model for free-flap transfer has been developed in the rat. This "thigh flap" is an osteomyocutaneous free flap of bone (femur), muscle (thigh), and skin (groin) based on the femoral vessels. The flap is harvested from the left groin and thigh of an inbred female rat and is transferred to a subcutaneous pocket in the left groin of a male rat of the same inbred strain. The femoral vessels supplying the flap are anastomosed end-to-end with the femoral vessels of the recipient. Thirty flaps have been transferred, with 5 technical failures. Three of the remaining 25 flaps developed necrosis within 24 hours. The other 22 flaps remained viable until the rat was sacrificed at 7 days. The survival rate of the thigh flap was thus 88 percent. The model is suitable for use in metabolic, vascular, and immunologic studies of composite free flaps. PMID- 3336655 TI - The critical relationship between free radicals and degrees of ischemia: evidence for tissue intolerance of marginal perfusion. AB - Skin-flap ischemia has been associated with the presence of free radicals. In this study, two enzyme systems involved in free-radical metabolism were used to compare a distal skin flap to a skin graft. Forty-two rats were divided into several test groups. A 10 X 3 cm dorsal rat flap was used, and tissue biopsies for xanthine oxidase and malonyldialdehyde (MDA) were obtained 2.5, 5.5, and 8.5 cm from the base of the flap at the hours given. In group I (control), the flap was outlined but not elevated, and biopsies were obtained. In group II, the flap was elevated, and biopsies were obtained at 6 hours. In group III, the flap was elevated, the distal 4 X 3 cm was amputated and replaced as a full-thickness skin graft, and biopsies were obtained at 6 hours. In group IV, the flap was elevated, and biopsies were obtained at 12 hours. In group V, the flap was treated as in group III, and biopsies were obtained at 12 hours. In group VI, the flap was elevated, and biopsies were obtained at 24 hours. In group VII, the flap was treated as in group III, and biopsies were obtained at 24 hours. RESULTS: Xanthine oxidase was significantly higher in all distal biopsies compared to proximal biopsies. Xanthine oxidase also increased with time. Malonyldialdehyde increased over time as well as with distance from the flap base. Distal flap biopsies at 24 hours had greatly increased levels of malonyldialdehyde compared to skin grafts (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336657 TI - An assessment of the effects of internal neurolysis on a chronically compressed rat sciatic nerve. AB - Chronically compressed nerves were treated with three surgical modalities. Simple decompression was compared to internal neurolysis with and without the addition of extrafascicular steroid. Electrophysiologic, histologic, and morphometric assessments were performed. Compressed control nerves demonstrated changes compatible with severe nerve compression (Wallerian degeneration). With simple decompression, improvement in histologic and electrophysiologic parameters occurred. When internal neurolysis was added to the decompression, further improvement in histologic and electrophysiologic parameters was noted. There was no added improvement with the addition of steroids. PMID- 3336658 TI - Is there medicine after residency? PMID- 3336659 TI - Surgical correction of entropion and ectropion in the same lid. AB - A patient with medial ectropion and lateral entropion of the same lower lid is presented, and the surgical management of this unusual condition utilizing a horizontal lid-shortening, orbicularis sling procedure, fixation of the posterior and anterior lamellae of the lid, and resection of the tarsal conjunctival layer is described. We believe that the key to the successful management of this condition lies in treating each component surgically as if it were a separate entity, and by using a combination of surgical techniques, both eyelid malpositions can be corrected. PMID- 3336660 TI - An operating table for hand surgery. AB - The construction details for an inexpensive, easy-to-build operating table for hand surgery have been described. The table was specifically designed according to the needs of those working with it. It has been in daily use for over 2 years and has proved to be a popular product with all staff members. PMID- 3336661 TI - The ideal needleholder. PMID- 3336662 TI - Lentoid. PMID- 3336663 TI - Nerve injury in lower-extremity trauma. PMID- 3336664 TI - Some additional comments on the surgical management of drooling. PMID- 3336665 TI - Care of replantation materials. PMID- 3336666 TI - The Vac-Pac. PMID- 3336667 TI - Confessions from the bottom. PMID- 3336668 TI - MR imaging of the pelvis. PMID- 3336669 TI - Adenomyosis: diagnosis with MR imaging. AB - Magnetic resonance (MR) imaging characteristics of adenomyosis were studied in eight women (aged 37-49 years) who underwent hysterectomy, and detailed radiologic/pathologic correlation was conducted in all cases. Adenomyosis produced diffuse and smooth uterine enlargement. The extent of the lesion was clearly identified on images obtained with long repetition time and long echo time; a diffuse, low-intensity area accompanied by tiny high-intensity spots was seen subjacent to the endometrium. The area appeared as a localized or diffuse thickening of the junctional zone because it was often isointense with this zone. Pathologic examination confirmed that the extent of adenomyosis correlated well with the low-intensity region on MR images and that both hemorrhagic areas and nonbleeding endometrial tissue corresponded to the high-intensity spots. The lesion consisted of distorted and compacted smooth muscle cells, but microscopic studies failed to explain the definitive difference in intensity between areas of adenomyosis and myometrium. PMID- 3336670 TI - Posttraumatic impotence: angiographic evaluation. AB - The onset of impotence was related to penile trauma in ten of 90 patients who underwent angiography. Angiographic results facilitated diagnosis in all patients. Trauma was secondary to a variety of injuries including fractures, soft tissue perineal injuries without fractures, and repeated perineal pounding during long, jarring drives. The final diagnosis was arteriogenic impotence (n = 2), arteriovenogenic impotence (n = 2), venogenic impotence (n = 3), venoneurogenic impotence (n = 1), neurogenic impotence (n = 1), and psychogenic impotence (n = 1). Proper angiographic evaluation required refined angiographic techniques such as selective magnification pharmacoarteriography, pharmacocavernosography, and pharmacocavernosometry. A variety of therapeutic options were either recommended or applied, depending on the angiographic findings. These included venous ligation, arterial bypass, injections of papaverine hydrochloride, and insertion of penile prostheses. PMID- 3336671 TI - Management of the asymptomatic patient with a unilateral adrenal mass. PMID- 3336672 TI - Upper abdomen: CT findings following partial hepatectomy. AB - The appearance on computed tomographic (CT) scans of the upper abdomen after partial hepatectomy is complex. The findings expected at CT should not be confused with those of surgical complications, such as abscess, biloma, or hematoma. The findings on CT scans and the records of 17 patients who had undergone partial hepatectomy for malignancy were reviewed. Operations included wedge resection, left medial and lateral segmentectomies, left lobectomy, right subsegmentectomy, right lobectomy, and extended right lobectomy (trisegmentectomy). When partial hepatectomy had been performed with no complications, findings at CT included a small region of low attenuation at the surgical margin, probably due to transient accumulation of blood and bile; a right pleural effusion; extraluminal gas; shift of abdominal organs; hepatic regeneration; and fat attenuation at the resection margin representing the omental patch placed at surgery. Findings associated with surgical complications- such as abscess, biloma, and hematoma--included large or high-attenuation perihepatic and subphrenic fluid collections that did not conform to the resection margin. PMID- 3336673 TI - Ischemic or infarcted bowel: CT findings. AB - Computed tomography (CT) has been used in the evaluation of patients with suspected bowel ischemia or infarction. To assess its efficacy in this setting, the CT scans and medical records of 23 patients with proved bowel ischemia or infarction were retrospectively reviewed. Surgery or autopsy revealed that the colon was involved in 17 patients, the small bowel in 13, and the stomach in one (some patients had multiple sites of involvement). The prospective CT interpretation enabled a specific diagnosis of bowel ischemia or infarction in only six of 23 patients (26%). However, in 13 patients (56%), the CT scans were considered useful in patient treatment. A retrospective review of CT scans indicated that bowel dilatation was present in 13 of 23 patients (56%); however, it was not always restricted to the ischemic area. Six of 23 patients (26%) had bowel wall thickening greater than 3 mm, but two had thickening in areas that were not ischemic at surgery. Pneumatosis intestinalis and portal venous gas were seen in only five patients (22%) and three patients (13%), respectively. Superior mesenteric artery thrombosis and free intraperitoneal gas were each found in only one patient (4%). PMID- 3336674 TI - Echo-planar pediatric imager. AB - Practical constraints make it difficult to build large-aperture echo-planar magnetic resonance (MR) imagers. The implementation of a pediatric imager and its performance are described. Spatial resolution and signal-to-noise levels comparable to those of 1982 state-of-the-art MR imagers have been achieved in imaging times of 0.05-0.15 seconds. T1 and T2 information are obtainable in the echo-planar mode. A major issue is that of chemical-shift displacements. PMID- 3336675 TI - Normal maturation of the neonatal and infant brain: MR imaging at 1.5 T. AB - The pattern of normal white-matter maturation as demonstrated with high-field strength magnetic resonance (MR) imaging was investigated. Eighty-two neurologically normal infants were examined with a 1.5-T unit with use of spin echo T1-weighted and T2-weighted pulse sequences. The infants ranged in age from 4 days to 2 years. The images were assessed for qualitative changes of white matter relative to gray matter in 14 anatomic areas of the brain and correlated with the patient's age. The MR images showed that changes of brain maturation occur in an orderly manner, commencing in the brain stem and progressing to the cerebellum and the cerebrum. Changes caused by brain myelination were seen earlier on T1-weighted images than on T2-weighted images, possibly because of T1 shortening by the components of the developing myelin sheaths. The later changes on the T2-weighted images correlated best with the development of myelination as demonstrated with histochemical methods. T1-weighted images were most useful in the monitoring of normal brain development in the first 6-8 months of life; T2 weighted images were more useful after 6 months. The milestones in the MR appearance of normal maturation of the brain are presented. Persistent areas of long T2 relaxation times are seen superior and dorsal to the ventricular trigone in all infants examined and should not be mistaken for ischemic change. PMID- 3336676 TI - Nonrefractory temporal lobe epilepsy: 1.5-T MR imaging. AB - Thirty-one patients with temporal lobe epilepsy (TLE) of mild to moderate severity, well controlled by pharmacotherapy (nonrefractory TLE), and with negative findings at computed tomography, were studied with magnetic resonance (MR) imaging at 1.5 T. Examination disclosed significant findings in 16 patients: mesial temporal abnormalities (n = 9), basitemporal abnormalities (n = 2), and alterations in frontoparietal white matter (n = 5). Coronal views and sequences with a 120-msec echo time (TE) depicted lesions in 16 patients; axial views depicted lesions in only nine of 16 patients; sequences with a 35-msec TE depicted lesions in only ten. These results underline the importance of screening with MR imaging in nonrefractory TLE patients and suggest that the MR imaging sequence of choice is a thin-section, coronal, T2-weighted sequence. PMID- 3336678 TI - Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. AB - The authors reviewed magnetic resonance (MR) images of 474 consecutive patients referred for lumbar spine MR imaging. Type 1 changes (decreased signal intensity on T1-weighted spin-echo images and increased signal intensity on T2-weighted images) were identified in 20 patients (4%) and type 2 (increased signal intensity on T1-weighted images and isointense or slightly increased signal intensity on T2-weighted images) in 77 patients (16%). In all cases there was evidence of associated degenerative disk disease at the level of involvement. Histopathologic sections in three cases of type 1 change demonstrated disruption and fissuring of the end plates and vascularized fibrous tissue, while in three cases of type 2 change they demonstrated yellow marrow replacement. In addition, 16 patients with end-plate changes documented with MR were studied longitudinally. Type 1 changes in five of six patients converted to a type 2 pattern in 14 months to 3 years. Type 2 changes in ten patients remained stable over a 2-3-year period. These signal intensity changes appear to reflect a spectrum of vertebral body marrow changes associated with degenerative disk disease. PMID- 3336677 TI - Chordomas: MR imaging. AB - Twenty histologically verified intracranial and upper cervical chordomas were retrospectively studied with both magnetic resonance (MR) imaging and computed tomography (CT), and the advantages of each modality were compared with regard to three criteria: detection of tumor, delineation of extent of tumor, and characterization of tumor. MR imaging and CT were equivalent in permitting the detection of chordomas. MR imaging was considerably better in delineating the full extent of the tumor, which would influence establishment of treatment. MR imaging also provided a degree of histologic specificity that would be useful in prognosis. PMID- 3336679 TI - Spondyloarthropathy of the cervical spine in long-term hemodialysis. AB - Changes stimulating osteomyelitis have recently been described in patients undergoing long-term hemodialysis. These consist of disk-space narrowing and irregularity of adjacent end plates. However, the characteristic prevertebral mass and clinical evidence of infection are often absent. In the appropriate clinical situation, although plain radiography and computed tomography have been helpful, magnetic resonance imaging may be more definitive in excluding infection and may obviate biopsy. The authors' imaging experience with five patients with this entity forms the basis of this report. PMID- 3336680 TI - Musculoskeletal infection of the extremities: evaluation with MR imaging. AB - Magnetic resonance (MR) imaging was performed in 17 patients, 11-84 years of age, referred for evaluation of possible osteomyelitis involving the appendicular skeleton. MR imaging permitted successful identification of osteomyelitis in ten patients (four acute, two subacute with Brodie abscess, two chronic, and two acute with septic arthritis) and of cellulitis in the absence of osteomyelitis in four patients, including one with a soft-tissue abscess. Active osteomyelitis was excluded in three patients. Both T1- and T2-weighted spin-echo sequences were needed to evaluate osteomyelitis. T2-weighted images were needed to identify foci of active infection. MR images provided more accurate and detailed information regarding the extent of involvement than did radionuclide bone scans, computed tomographic scans, or standard radiographs. It permitted the differentiation of septic arthritis or cellulitis from osteomyelitis. In this limited series, MR imaging was particularly useful for seeking foci of active infection in areas of chronic osteomyelitis complicated by surgical intervention or fracture. PMID- 3336681 TI - Rotator cuff impingement syndrome: MR imaging. AB - Ten patients with clinically suspected rotator cuff impingement syndrome were evaluated with magnetic resonance (MR) imaging, double contrast arthrography, and conventional radiography. An area of increased signal intensity in the tendinous portion of the rotator cuff was seen in eight of ten patients on images obtained with a short repetition time (TR) and short echo time (TE) and those obtained with a long TR and long TE with spin-echo sequences. Microscopic findings, available in five patients, indicated that these areas of increased intensity corresponded to degeneration and inflammation of the rotator cuff. A previously injected long-acting steroid preparation combined with a local anesthetic, which also produces an area of increased signal intensity on long TR, long TE images, can cause problems with image interpretation. No tears of the rotator cuff were detected with MR imaging. However, a full-thickness cuff tear was detected with arthrography in three patients. Although based on a relatively small group of patients, these preliminary findings suggest that MR imaging is capable of demonstrating rotator cuff abnormalities in patients with impingement syndrome. PMID- 3336682 TI - Femoral head avascular necrosis: MR imaging with clinical-pathologic and radionuclide correlation. AB - A retrospective evaluation of magnetic resonance (MR) imaging for the detection of avascular necrosis (AVN) of the femoral head was performed in 49 patients (85 hips) with clinical suspicion of AVN. Positive findings at bone biopsy or evidence on plain radiographs was considered proof of AVN. Absence of clinical symptoms and of radiographic findings for a minimum of 18 months after MR imaging was considered evidence of the absence of AVN. All patients were studied with plain radiography and technetium-99m methylene diphosphonate bone scintigraphy. Five hips had negative MR images, positive findings at bone marrow biopsy, positive bone pressure measurement (BMP), and positive bone scans. A comparison between MR images and bone scans showed MR imaging to be superior, with a sensitivity of 88.8% (vs. 77.5%) and a specificity of 100% (vs. 75%). BMP was the most sensitive (92%) but least specific test (57%). PMID- 3336684 TI - Change in human cardiac rhythm induced by a 2-T static magnetic field. AB - The influence of a 2-T static magnetic field on the cardiac rhythm was studied with 24-hour electrocardiographic monitoring in 12 healthy volunteers for 1 hour before exposure, 1 hour during exposure, and 22 hours after exposure. Four other subjects were exposed to 1 T, and nine control subjects were exposed to 0 T. In the 2-T group, the mean cardiac cycle length (CCL) was 912 msec +/- 83 before exposure. A significant 17% increase in CCL was observed after 10 minutes of exposure. No further significant variation was observed during exposure, and the CCL was back to preexposure values 10 minutes after exposure. No other arrhythmogenic effect was noted during the 24-hour monitoring. No statistically significant change was observed at either 0 or 1 T. The magnetically induced blood-flow potentials superimposed on the T wave were observed. The CCL increase during exposure could reflect a direct or indirect effect of magnetic fields on the sinus node, which is probably harmless in healthy subjects. However, its safety in dysrhythmic patients remains to be determined. PMID- 3336683 TI - Ankle tendons: evaluation with CT. AB - Computed tomographic (CT) analysis of 21 clinically suspected ankle tendon injuries was performed in 18 patients. In six of the 21 ankles surgical exploration was done, and in one ankle evaluation was done while the patient was under anesthesia. In all seven cases the CT findings were confirmed and in three the clinical diagnosis was disproved. CT provided additional information and helped guide treatment in the majority of patients studied. Thus CT is an accurate, noninvasive modality for assessing ankle tendon injuries. PMID- 3336685 TI - FRODO pulse sequences: a new means of eliminating motion, flow, and wraparound artifacts. AB - Magnetic resonance images of the spine, chest, abdomen, and pelvis are commonly degraded by ghost artifacts. The authors have developed a new technique named FRODO (Flow and Respiratory artifact Obliteration with Directed Orthogonal pulses) to suppress these artifacts. Signal from tissues responsible for the artifacts is eliminated by use of radio frequency pulses specifically optimized for high selectivity to saturate proton magnetization over one or more independently defined slabs (large rectangular volumes) of tissue. Ghost artifacts from pulsatile flow in the heart and blood vessels, as well as from respiratory motion and swallowing, are suppressed. Additional applications of this technique include elimination of intraluminal signal in blood vessels and suppression of wraparound artifact along the phase-encoding axis. Preliminary clinical experience suggests that the FRODO technique, in conjunction with other flow compensation methods, may provide a definitive solution to the problem of motion in spine imaging. FRODO pulse sequences may also prove useful for imaging of blood vessels, heart, abdomen, and other areas where motion, flow, or wraparound artifacts limit image quality. PMID- 3336687 TI - Hippel-Lindau disease: MR imaging. AB - Hippel-Lindau disease is an auto-somal-dominant disorder characterized by tumors arising from the central nervous system and abdominal viscera. Because of its progressive nature, frequent multisystem radiologic evaluation of affected persons and family members at risk is desirable for early detection and treatment. During a 2-year study, magnetic resonance (MR) imaging of the head, spine, and abdomen was used for screening and follow-up in 26 members of nine families with the disease. In addition to 13 previously diagnosed cases, five cases were newly diagnosed during the study. Lesions causing significant morbidity and mortality--such as cerebellar and spinal cord hemangioblastoma, renal cell carcinoma, and pheochromocytoma--were correctly depicted with MR imaging, sometimes before symptoms had developed and before the lesions could be seen with other imaging modalities. Central nervous system abnormalities were most clearly shown, but MR imaging also adequately demonstrated abdominal visceral abnormalities. It is therefore highly useful in the diagnosis and follow up of Hippel-Lindau disease. PMID- 3336686 TI - Quantitative flow measurement with the fast Fourier flow technique. AB - The fast Fourier flow method of magnetic resonance (MR) imaging offers a fast and efficient way of measuring quantitative flow for velocities within the range from several millimeters per second to more than 1 m/sec. When fast Fourier flow imaging is used in combination with echocardiographic gating, arterial flow can be determined and velocity versus time profiles can be generated. Because of the high spatial resolution, down to 0.3 mm, detailed examination of flow profiles is possible even in smaller vessels. The method works equally well on a low-field strength system operating at 0.23 T and on a high-field-strength system with 4.7 T field strength. Since the experiment is very fast, with acquisition times ranging from 4 seconds for a single-section experiment to about 4 minutes for the electrocardiographically gated variant, it can easily be combined with a conventional MR imaging examination. PMID- 3336689 TI - Sheath needle for liver biopsy in high-risk patients. AB - Addition of an outer plastic sheath to a standard biopsy needle allows fluoroscopically monitored embolization of the biopsy site and needle tract with gelatin particles, thus reducing the risk of postbiopsy hemorrhage. This method has been used instead of the transjugular technique to perform liver biopsies in 22 patients considered to be at high risk for hemorrhage from biopsy performed with conventional techniques. A specimen adequate for diagnosis was obtained in 21 of the 22 patients. No patient exhibited clinical signs of postbiopsy hemorrhage. PMID- 3336688 TI - Improved financial management of the radiology department with a microcosting system. AB - The basic unit of service in radiology is the examination or procedure and its associated costs such as film, medical and surgical supplies, personnel, equipment depreciation, and overhead. The appropriate allocation of all operating costs to the specific examination types is the purpose of the microcosting system. Microcosting programs use data from hospital expense and payroll systems and data from a radiology information management system. These data are loaded into a computer spread sheet program for the microcosting computations. The results from using this system include better understanding of costs, accurate budget projections, confidence in negotiating discounts, and improved efficiency and reduced costs. PMID- 3336690 TI - Epiphyseal growth plate: evaluation with modified coronal CT. AB - A method of modified coronal computed tomography (CT) was developed for examination of epiphyseal growth plate arrest and neoplasms near the growth plate. Twenty-four patients were examined with this technique (26 examinations). In all cases, the growth plate and adjacent regions were well demonstrated. PMID- 3336691 TI - Signal-to-noise ratio and section thickness in two-dimensional versus three dimensional Fourier transform MR imaging. AB - The efficiency and quality of three-dimensional Fourier transform (3DFT) magnetic resonance imaging were evaluated and compared with those of 2DFT imaging. For a fixed imaging time and number of sections, 3DFT imaging with conventional spin echoes always had a worse signal-to-noise ratio (S/N) than did 2DFT imaging, when both were optimized with respect to choice of repetition time (TR). With partial flip magnetic resonance (MR) imaging, S/N was nearly equal for 2DFT and 3DFT imaging when both were optimized with respect to TR and flip angle. 3DFT imaging can have cross-section artifacts that exceed those of 2DFT imaging. For very thin sections these artifacts may be lessened, and 3DFT imaging can achieve this with smaller gradient pulses. Over-all, 3DFT imaging was found to be advantageous only for the very-thin-section imaging and in combination with partial-flip MR imaging. PMID- 3336692 TI - Economic and utilization analysis of MR imaging units in the United States in 1987. AB - The 72 most experienced magnetic resonance (MR) imaging installations were surveyed for operational and economic data from January or February 1987. The typical MR imaging installation was operating 69 hours and examining 58 patients per week, with 82% of the studies being neuroradiologic. The mean fees were $545 $603 for the technical component and $111-$232 for the professional component, with a higher charge for body procedures. The mean annual gross revenues were $1,193,000, and revenues after deductions totaled $1,014,000. Estimated expenses for a typical MR imaging installation were $968,000, with a net annual revenue of $46,000 or more. Compared with 1985 data from the same study group, weekly patient volume and hours of operation have increased--from 35 to 58 patients and from 54 to 69 hours. Installations are more efficient, as the number of patients examined per hour has increased from 0.6 to 0.8. Demand for MR imaging is growing, as the outpatient scheduling delay has increased from 5.3 to 11.4 days. The financial position of MR imaging units has markedly improved from a previous loss of $460,000 to an estimated current gain of +46,000 or more annually. MR imaging installations have shown improvement by several objective criteria - patient throughput, operational efficiency, and financial net revenues. PMID- 3336693 TI - Mammography screening and the self-referred woman. AB - There are no easy answers to the question of whether a mammography screening practice should accept self-referred women. The major reason for doing so is the fact that many women are not being screened either because their primary care physicians do not initiate mammography screening referrals or because they do not have a physician at all. However, this compelling argument is at least partially countered by the numerous problems encountered when practices accept self referred women, including potential adverse medicolegal consequences, tedious and time-consuming reporting requirements, the possibility of turf battles with referring physicians, and, especially if breast physical examination is not offered, somewhat increased costs of screening. The ultimate decision of whether self-referred women are accepted will probably be based on an analysis of the prevailing conditions in each radiologist's local environment. Because local conditions vary greatly, so may the final decision vary. However, once the choice is made, steps should be taken to provide ready access to screening while also reducing the frequency with which self-referral-related problems occur. To this end, those radiologists who decide to accept self-referred women, particularly if screening is done with mammography alone, should attempt to convert as many self referred cases as possible into patient-initiated physician referrals. Similarly, radiologists who decide to screen on a referral-only basis should develop mechanisms that make it very easy for self-referred women to obtain physician referrals. PMID- 3336694 TI - Productivity standards for technologists: how to use them. PMID- 3336695 TI - Advice to authors. PMID- 3336696 TI - Trabecular bone mineral density measurement in vivo. PMID- 3336697 TI - Adrenal gland: MR imaging. PMID- 3336698 TI - Articular erosions in the hands and wrists in patients undergoing long-term maintenance hemodialysis. PMID- 3336699 TI - Serpentine (not serpiginous) vessels in spinal arteriovenous malformations. PMID- 3336700 TI - Can mammography exclude cancer? PMID- 3336701 TI - In vitro study of high-pressure catheters and various contrast agents. AB - The versatility of angiography has been expanded by the introduction of low osmolality contrast agents; high-pressure, high-flow catheters with small outer diameters; and the use of contrast agents with low iodine concentrations. These changes have resulted in the need for a review of the physical factors that influence the flow of contrast agents through flush catheters. Various contrast agents were injected through several types of high-pressure, high-flow catheters with small outer diameters, and the flow rates were measured. Great differences in the viscosities of contrast agents resulted in proportionately smaller differences in maximum flow rates, and warming the contrast agent from room to body temperature had little effect on the maximum flow rate, except for the most viscous contrast agents. The maximum flow rates of the new low-osmolality contrast agents did not differ significantly from those of conventional ionic contrast agents of similar iodine concentration. With unheated contrast agents, iodine delivery was more rapid for contrast agents with iodine concentrations of 280-300 mg/mL. PMID- 3336702 TI - Cardiovascular disease: evaluation with MR phase imaging. AB - Magnetic resonance phase images are derived from conventional spin-echo (SE) pulse sequences and display properties of proton movement that occurs with blood flow. SE magnitude and phase images were obtained and retrospectively evaluated in 21 patients referred for potential cardiovascular abnormalities in which intracardiac or intravascular signal was detected. Abnormalities included intravascular and intracardiac thrombus, aneurysm, aortic dissection, flow alteration, atherosclerotic disease, and congenital cardiac anomaly. Thrombosis (six cases) was successfully differentiated from flow-related signal (15 cases) by comparing phase images with SE magnitude images; in cases of thrombosis, there was no phase shift in corresponding areas of increased signal intensity. In comparison, SE magnitude signal intensities alone were not an accurate indicator in differentiating thrombus from flow-related enhancement. Because phase images are sensitive for identifying flow, the SE magnitude signal of intravascular tumor or thrombus can be differentiated from that of flow effects with more clinical confidence. PMID- 3336703 TI - The self-referred mammography patient: a new responsibility for radiologists. AB - A mammography screening program was initiated in which self-referred women were accepted for examination. Two views of each breast were obtained, and no physical examination was performed. Reports were sent to each patient and to the patient's primary care physician, if she had one. The program was successful in that the number of examinations performed per day increased from 36 to 80 within 6 months. Approximately 50% of the women who came for screening did so at their own request. Self-referred women with abnormal findings on mammograms who did not have a primary care physician were contacted by phone and told of the results. Advice was given for further evaluation, and the patient was referred to a local physician if she still did not know of one. Further workup in patients with abnormal findings was verified with the use of computer tracking and follow-up phone calls. Self-referral is an important component of screening mammography, but it places added responsibility on the radiologist in cases in which there is no referring physician. PMID- 3336704 TI - Bronchogenic carcinoma metastatic to normal-sized lymph nodes: frequency and significance. AB - CT staging of mediastinal lymph node metastases from bronchogenic carcinoma is a subject of considerable controversy. The frequency of metastases to normal-sized lymph nodes is a critical issue related to the sensitivity of CT. The authors prospectively examined 42 patients with bronchogenic carcinoma with CT; in 39, careful surgical-pathologic correlation of mediastinal lymph node status was possible. Only 7% had metastases limited to mediastinal lymph nodes that were normal-sized at CT. This reflected a low overall frequency of metastases to normal-sized nodes and several diagnostic factors that converted potentially false-negative studies into true-positive CT studies. In this small series, metastases to enlarged nodes were more likely to have extracapsular spread of tumor, a poor prognostic factor. Overall, the authors do not consider metastases to normal-sized mediastinal lymph nodes to be a major problem in CT staging of non-small cell lung cancer. PMID- 3336705 TI - Resectable stage III lung cancer: CT, surgical, and pathologic correlation. AB - The new International Staging System identifies a subset of patients with stage III lung cancer who have improved survival rates after surgical resection. The computed tomographic (CT), surgical, and pathologic findings in 26 patients with completely resected stage IIIa lung cancer were reviewed. Preoperative CT scans accurately demonstrated chest wall invasion in only two of ten patients with chest wall or diaphragmatic invasion. CT demonstrated pericardial involvement in only one of three patients. Tumor extension to within 2 cm of the tracheal carina was seen with CT in one of three patients. Eleven of 26 patients had limited ipsilateral mediastinal (N2) disease; eight of 11 had affected nodes greater then 10 mm on CT scans. As previously shown, CT is of limited value in the assessment of chest wall, mediastinal, pleural, or pericardial tumor extension; however, such extension does not preclude complete resection. Ipsilateral node involvement does not preclude surgery. Familiarity with the new staging system and awareness of what constitutes potentially resectable disease are necessary for an adequate assessment of CT findings. PMID- 3336706 TI - Normal and diseased isolated lungs: high-resolution CT. AB - High-resolution computed tomography (CT) scans of 12 isolated, inflated, fresh lungs obtained at autopsy were compared with thin, paper-mounted lung sections obtained at the same levels. In six lungs considered intrinsically normal, high resolution CT showed normal interlobular septa and pulmonary arteries in the lobular core, but lobular bronchioles were not visible. Edematous fluid resulted in thickening and increased visibility of interlobular septa. In three emphysematous lungs, high-resolution CT accurately demonstrated the degree of emphysema and suggested its centrilobular nature. In two lungs with honeycombing, cysts lined by fibrosis were easily seen on high-resolution CT scans. In less severely involved areas, septal thickening and intralobular fibrosis were seen on high-resolution CT scans, but small (1 mm) cysts were invisible. High-resolution CT was able to demonstrate some features of the normal secondary pulmonary lobule and structural alterations produced by various diseases. PMID- 3336707 TI - Pneumothorax: radiologic treatment with small catheters. AB - In many institutions, the standard treatment of symptomatic and large pneumothoraxes has been with surgically placed large-bore (22-32-F) chest tubes. During the past 3-4 years, the authors used small catheters (7, 8.2, and 9.4 F) to decompress 30 pneumothoraxes (15 under tension) resulting from percutaneous lung biopsy. The catheters were inserted under computed tomographic or fluoroscopic guidance for the treatment of large (greater than 35%) or symptomatic pneumothoraxes. Twenty-eight of 30 patients were treated successfully with the small catheters alone; two patients underwent surgical placement of 32-F tubes (4 and 12 hours later) because of incomplete resolution of the pneumothoraxes. This series demonstrates that small-caliber catheters effectively decompress pneumothoraxes and that they can be inserted expeditiously by radiologists in the radiology department. PMID- 3336708 TI - Transthoracic needle aspiration biopsy: evaluation of the blood patch technique. AB - A study was undertaken to evaluate the effectiveness of the blood patch technique in the prevention of pneumothorax after transthoracic needle aspiration biopsy. A total of 140 needle biopsies were performed with a coaxial system. Two groups of patients were defined according to whether or not autologous blood was injected into the introducing needle as it was withdrawn after needle aspiration biopsy. Fifty-two biopsies were performed with the blood patch technique (group A), while 88 biopsies were performed without the blood patch technique (group B). The frequency of postbiopsy pneumothorax was 28.8% (15 of 52 patients) in group A and 34.1% (30 of 88 patients) in group B. Chest tube insertion was required in 7.7% (four of 52 patients) in group A and in 9.1% (eight of 88 patients) in group B. There was no statistically significant difference in pneumothorax rate and chest tube insertion rate between the two groups (P greater than .05). In this series of 140 biopsies, the blood patch technique failed to affect the rate of pneumothorax after transthoracic needle aspiration biopsy. PMID- 3336709 TI - Accuracy of CT in detection of persistent or recurrent ovarian carcinoma: correlation with second-look laparotomy. AB - Computed tomographic (CT) studies in 39 patients with advanced ovarian carcinoma were retrospectively evaluated to assess their accuracy in detection of persistent or recurrent disease as seen at second-look laparotomy (SLL). Twenty patients were studied before June 1983 (group 1), and 19 patients were studied afterward (group 2). There were 16 true-positive, ten true-negative, two false positive, and 11 false-negative examinations. Five false-negative studies resulted from microscopic disease found at SLL. In group 1, there were eight false-negative studies. In five, macroscopic disease was not recognized. In group 2, there were three false-negative studies; in one, macroscopic disease was not recognized. Statistical analysis showed an observable improvement in the accuracy in group 2. The differences included use of faster scanners, routine use of thin sections for the pelvis, and air-contrast colonic opacification in group 2. These results suggest that carefully performed scanning on state-of-the-art equipment may have a higher accuracy in documenting persistent or recurrent macroscopic tumor. PMID- 3336710 TI - Adrenal masses in oncologic patients: functional and morphologic evaluation. AB - The role of adrenocortical scintigraphy in the evaluation of unilateral adrenal masses detected with computed tomography (CT) in 28 oncologic patients with normal adrenal function was studied prospectively with the use of NP-59 (iodine 131-6-iodomethyl-19-norcholesterol). The diagnosis was proved by means of percutaneous fine-needle aspiration cytologic examination in 20 patients, surgical biopsy in one, and clinical and CT follow-up in seven. In 14 of the 28 patients, there was increased uptake of the NP-59 on the side of the adrenal mass detected at CT (concordant uptake). Thirteen of the 14 masses with concordant uptake were greater than 2 cm in diameter, and one was 1.5 cm; all were found to be adenomas. In 11 of 28 patients there was decreased uptake on the side of the mass detected at CT (discordant uptake). None of these 11 masses were adenomas; nine were metastases and two were adrenal cysts. Uptake was indeterminate (symmetric) in three patients, two of whom had adrenal adenomas and one an adrenal metastasis; each mass with indeterminate uptake was less than 2 cm in diameter. PMID- 3336712 TI - Inferior vena cava filters: in vitro comparison of clot trapping and flow dynamics. AB - Using a flow model that simulated the inferior vena cava (IVC), the authors conducted an in vitro comparison of the Mobin-Uddin (MU), Kimray-Greenfield (KG), Amplatz spider (A), Gunther basket (G), Simon nitinol (SN), and bird's nest (BN) filters. The following parameters were evaluated: clot-trapping capacity and flow dynamics, which included measurements of pressure gradients across filters and assessment of flow patterns. The MU, A, G, SN, and BN filters trapped an average of 80%-100% of small clots and 100% of large clots. The KG filter, in a central position, trapped 0%-10% of small clots and 60%-100% of larger clots. In the eccentric position, the KG filter trapped only 20% of all clots. The BN and SN filters showed the least flow turbulence. Moderate turbulence was observed with the G and KG filters, while the MU and A filters showed marked turbulence. The current standard KG filter allowed the passage of small and large clots. When specific parameters were considered--such as clot-trapping capacity and flow dynamic performance--the BN, SN, and G IVC filters were superior to the other filters that were tested. PMID- 3336711 TI - Adrenal masses: characterization with T1-weighted MR imaging. AB - The ability of a T1-weighted spin-echo magnetic resonance (MR) sequence to allow differentiation of benign from malignant adrenal masses at 0.5 T was investigated in 28 patients with 35 adrenal masses. All nine lesions with an adrenal mass liver signal intensity ratio of 0.71 or less were metastases, and all 15 with a ratio of 0.78 or more were adenomas. Eleven masses (31%)--including six adenomas, three metastases, a pheochromocytoma, and a neuroblastoma--had ratios between these values. Nine of ten masses with adrenal mass-fat intensity ratios of 0.35 or less were metastases, and all 12 with ratios of 0.42 or more were benign. Eleven masses (31%), four malignant and one benign, had ratios between these values. The ratios for two masses could not be calculated due to lack of fat. The specificity of T1-weighted MR imaging in differentiating benign from malignant adrenal masses appears similar to that reported for T2-weighted imaging. However, significant overlap occurred, as has also been reported for T2-weighted imaging. While both imaging sequences may help distinguish benign from malignant adrenal masses in some cases, biopsy is still necessary when an accurate histologic diagnosis is essential. PMID- 3336713 TI - Deep venous thrombosis evaluation with limited-flip-angle, gradient-refocused MR imaging: preliminary experience. AB - Sixteen patients (17 lower extremities) were prospectively examined with venography and limited-flip-angle, gradient-refocused magnetic resonance (MR) imaging for the presence or absence of deep venous thrombosis. Thrombosed vessels showed decreased-to-absent signal intensity, while patent vessels had high signal intensity. In 16 of 17 extremities, MR images allowed accurate detection and localization of the thrombi found with venography. In the remaining extremity, MR imaging allowed correct identification of thrombus in the iliac and femoral veins but incorrectly demonstrated clot in the calf and popliteal veins. MR imaging with limited-flip-angle, gradient-refocused pulse sequences appears to be a sensitive, noninvasive means of detecting deep venous thrombosis. PMID- 3336714 TI - Arterial occlusions in neonates: use of fibrinolytic therapy. AB - For neonates with ischemia of an extremity or extensive thrombosis of the aorta after umbilical artery catheterization, prompt recognition and management decisions are necessary. The cases of eight infants with symptomatic thrombosis who were treated with fibrinolytic agents were retrospectively reviewed to study means of diagnosis and response to therapy. Peripheral thrombosis was seen in two otherwise healthy infants; fibrinolytic therapy produced complete lysis in one and partial lysis in the other. The six infants with central thrombosis presented with low Apgar scores and multiple clinical problems; umbilical catheters were already in place. To assess the clot, real-time sonography was performed in all six patients, and umbilical arteriograms were obtained in five. Fibrinolytic therapy produced complete lysis of clot in five of the six infants. The one death occurred in a premature infant in whom a large intracranial hemorrhage developed 6 hours after institution of therapy. PMID- 3336715 TI - Outpatient performance of invasive radiologic procedures in pediatric patients. AB - A retrospective review was done of the outcomes of 102 invasive radiologic procedures--including myelography, angiography and needle aspiration biopsy- performed on an outpatient basis in 94 pediatric patients. Four children had complications requiring visits to their physicians, but no patients required hospitalization after the procedure. With appropriate patient selection, invasive studies performed on an outpatient basis in infants, children, and adolescents are safe. PMID- 3336716 TI - Solid and papillary epithelial neoplasms of the pancreas: CT findings. AB - Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient. PMID- 3336717 TI - Splenic lymphoma: ferrite-enhanced MR imaging in rats. AB - Ferrite, a new magnetic resonance (MR) contrast agent, was evaluated in the detection and diagnosis of splenic lymphoma. Before administration of ferrite, normal rat spleens and spleens with diffuse lymphoma showed similar in vitro relaxation times and in vivo MR imaging signal-to-noise ratios (S/N). After the administration of ferrite (50 mumol Fe/kg), the T2 time of lymphomatous spleen was 27.0 msec +/- 2.9 (mean +/- standard deviation), which was significantly greater than that of normal spleen (10.7 msec +/- 1.5, P less than .005). The S/N of ferrite-enhanced in vivo MR images of lymphomatous spleen was 12.4 +/- 0.9, which was significantly greater than normal (5.7 +/- 0.2, P less than .005). Similar experiments with animal models of micronodular lymphoma also demonstrated that ferrite-enhanced MR imaging can distinguish micronodular lymphoma from normal spleen. Benign splenomegaly, studied with an animal model of erythroid hyperplasia, showed ferrite-enhanced MR tissue characteristics that were indistinguishable from those of normal spleen. PMID- 3336718 TI - Underuse of screening mammography by family physicians. AB - Although the American College of Radiology, the National Cancer Institute, and the American Cancer Society recommend screening mammography for women more than 40 years old, there is little compliance with these recommendations. Primary-care physicians are often reluctant to refer patients for the procedure, whereas the patients are usually willing to undergo the procedure. This survey documents the underuse of screening mammography by family physicians who are members of the Michigan Academy of Family Physicians. The underuse of mammography by this physician sample was due to two main factors: The physicians perceived far more disadvantages than advantages with mammography and perceived problems (with, e.g., equipment, effectiveness, and patient acceptance) as pervasive. To change the attitudes and referral behavior of family physicians, one must take into account the specific, negative perceptions of the procedure and place an emphasis on the initial referral, since subsequent referrals are easier to implement. PMID- 3336719 TI - Effects of image processing on nodule detection rates in digitized chest radiographs: ROC study of observer performance. AB - To evaluate the effects of image processing in digitized chest radiographs when high-resolution images are used, an examination was done in which the detection of pulmonary nodules in unprocessed digitized chest radiographs was compared with that in images that had undergone processing with two methods, adaptive filtration and histogram equalization. The processing techniques have been optimized in previous work to selectively enhance the retrocardiac and subdiaphragmatic areas without significant alteration of detail in the lung. Eight observers were shown 150 test radiographs (50 unprocessed, 50 processed with adaptive filtration, 50 processed with histogram equalization) containing 150 nodules. The results indicate a statistically significant (P less than .03) difference, with highest observer performance in the chest radiographs processed with adaptive filtration (median area under ROC curve = 0.78), compared with unprocessed images (median = 0.68) and chest radiographs processed with histogram equalization (median = 0.62). Performance in the lung was not significantly different. Adaptive filtration applied to selectively enhance underexposed areas of film images may improve nodule detection. Histogram equalization provided no improvement in performance. PMID- 3336720 TI - Lung lesions: correlation between viewing time and detection. AB - The influence of viewing time on the detectability of subtle and obvious lung cancers was studied. Frontal chest radiographs of 40 patients with subtle cancers, 40 patients with obvious cancers, and 40 healthy control subjects were shown to four observers for four different viewing times (0.25 second, 1 second, 4 seconds, and unlimited time). Receiver operating characteristic analysis was used to compare the detectability of lesions. Performance was degraded as viewing time decreased. The true-positive fractions for subtle and obvious cancers were 30% and 70% at 0.25 second and 74% and 98% at unlimited viewing time, respectively, for a given false-positive fraction of 20%. Thus, even with unlimited viewing time, the false-negative fraction for subtle cancers was 26%. The difference in detectability between subtle and obvious lung cancers was exaggerated at 1.0 second compared with 4 seconds and unlimited viewing time. The following conclusions were reached: (a) a substantial proportion of subtle lung lesions are missed, even with unlimited viewing time; (b) a large proportion of obvious lung cancers are detected with flash viewing; (c) the detectability of lesions decreases considerably as viewing time becomes less than 4 seconds; and (d) differences in detectability are exaggerated by short viewing times. PMID- 3336721 TI - Carotid bifurcation: MR imaging. Work in progress. AB - To devise and implement an in-plane magnetic resonance angiography examination of the carotid bifurcation capable of producing high-resolution images, the authors examined 19 normal carotid arteries and 14 patients with angiographically documented disease with two flow-correction techniques: a three-gradient, velocity-refocused technique with spin-echo (SE) and gradient-echo sequences, and a four-gradient velocity- and acceleration-corrected SE technique. With use of three equal gradients in the read direction, velocity-related phase changes were minimized by placing the dephasing gradient after the 180 degree pulse and near the read gradient. Acceleration effects were minimized through the use of short echo times and cardiac gating. Both velocity- and acceleration-produced phase changes were corrected with the four-gradient scheme but at the expense of some limitations in spatial resolution. Both techniques consistently produced satisfactory images of the carotid bifurcation in healthy individuals. However, the results indicate that the present gradient-phase modulation techniques have several drawbacks, including susceptibility to patient motion, overlapping with the jugular vein, and inability to image carotid stenosis accurately due to turbulence. PMID- 3336722 TI - Cervical spine: MR imaging with a partial flip angle, gradient-refocused pulse sequence. Part I. General considerations and disk disease. AB - A magnetic resonance imaging pulse sequence with a short repetition time (TR), short echo time (TE), partial flip angle, and gradient refocused echo was evaluated for the detection of cervical disk disease in a prospective study of 90 patients. These parameters were manipulated to adjust signal-to-noise ratio (S/N) and contrast: flip angle (3 degrees-18 degrees), TR (22-60 msec), and TE (12.5-25 msec). Flip angle had the greatest effect on S/N and contrast; its effect differed between axial and sagittal imaging. Cerebrospinal fluid S/N reached a peak at a smaller flip angle in sagittal imaging than in axial imaging. The useful range of flip angles depended on TR. Increasing TR had minimal direct effect on S/N or contrast, but because a longer TR allowed the use of larger flip angles for both axial and sagittal imaging, higher S/N could be achieved with similar contrast. This effect of increasing TR had to be balanced against increased imaging time and increased probability of motion artifact. Increasing TE decreased S/N, increased contrast, and increased magnetic susceptibility artifacts. For the diagnosis of cervical disk disease, the best sequence appears to be one with a very short TR, short TE, and small flip angles within a narrow range. PMID- 3336724 TI - Spinal cord artifacts from truncation errors during MR imaging. AB - The significance of linear regions of altered signal intensity that appear in sagittal magnetic resonance (MR) images along the length of the spinal cord was investigated. Examinations were performed on ten healthy volunteers and one patient with spinal cord edema. A 0.5-T or a 1.5-T MR system was used. Sampling related effects (Gibbs phenomenon) at spinal cord edges and cerebrospinal fluid interfaces can lead to different signal patterns within the spinal cord and canal. These artifacts cause problems in interpretation, especially with the use of small object-to-pixel size ratios, by obscuring anatomy and simulating pathologic conditions such as pseudosyringes. Analysis of these intensity variations and of their dependence on sampling may improve the clinical accuracy of MR imaging. PMID- 3336723 TI - Cervical spine: MR imaging with a partial flip angle, gradient-refocused pulse sequence. Part II. Spinal cord disease. AB - A magnetic resonance imaging pulse sequence (GRASS) with a short repetition time (TR), short echo time (TE), partial flip angle, and gradient refocused echo was prospectively evaluated for the detection of cervical cord disease that caused minimal or no cord enlargement in eight patients. Sagittal T2-weighted, cerebrospinal fluid (CSF)-gated images and sagittal and axial GRASS images were obtained in all patients. The following GRASS parameters were manipulated to determine their effect on signal-to-noise ratio (S/N) and contrast: flip angle (4 degrees-18 degrees), TR (22-50 msec), and TE (12.5-25 msec). Flip angle had the greatest effect on S/N and contrast. There were no differences between axial and sagittal imaging for the spinal cord or lesion. However, because the signal intensity of CSF did differ on sagittal and axial images and because this influenced the conspicuity of lesions, there was a difference in the useful flip angle range for axial and sagittal imaging. No one set of imaging parameters was clearly superior, and in all patients, the gated image was superior to the sagittal GRASS image in lesion detection. GRASS images should be used in the axial plane primarily to confirm spinal cord disease detected on sagittal CSF gated images. For this, a balanced approach is suggested (TR = 40 msec, TE = 20 msec, with flip angles of 4 degrees-6 degrees for sagittal and 6 degrees-8 degrees for axial imaging). PMID- 3336725 TI - Syrinx-like artifacts on MR images of the spinal cord. AB - Magnetic resonance (MR) imaging of the spinal cord frequently demonstrates, especially on sagittal sections, a central stripe that mimics a true syrinx. This syrinx-like manifestation of a truncation artifact occurs in objects having a width of only a few pixels and was demonstrated by calculations verified with phantom MR images. Healthy volunteers and two patients with a syrinx and cervical spondylosis, respectively, underwent MR imaging. By increasing the number of phase-encoding steps, decreasing the field of view, and switching phase- and frequency-encoding axes, the syrinx-like artifact can be eliminated. PMID- 3336726 TI - Knee arthrography. PMID- 3336727 TI - Chronic recurrent multifocal osteomyelitis. AB - Chronic recurrent multifocal osteomyelitis is a recognized condition that usually affects children and adolescents. It generally has a self-limited course, causing significant symptoms but leaving few, if any, residual changes in most cases. The authors undertook a retrospective review of the radiographs and medical records of 11 patients with chronic recurrent multifocal osteomyelitis. They found that not all patients have complete resolution of disease, and a small minority may be left with residual bone changes. Chronic recurrent multifocal osteomyelitis was originally reported in Switzerland; most reported cases are from Europe and Scandinavia. The disease is being recognized with increasing frequency in North America. PMID- 3336728 TI - Spinal compression fractures in osteoporotic women: patterns and relationship to hyperkyphosis. AB - A prospective study of thoracic and lumbar spinal fracture distribution and its relationship to thoracic kyphosis was performed in 87 women with osteoporosis. Anterior wedge fractures were most commonly seen in the midthoracic spine and about the thoracolumbar junction, whereas central compression fractures were most common from the first to the fourth lumbar levels. Solitary wedge fractures did not occur above the seventh thoracic vertebra, suggesting that a cause other than osteoporosis must be suspected in any patient with an isolated high thoracic fracture. Analysis of the spinal radiographs obtained in an additional 16 women without osteoporosis revealed that both forms of fracture were unusual in this small group with normal spinal mineralization. The number of anterior wedge fractures in the thoracic spine correlated (r = .546) with the degree of thoracic kyphosis. However, 19% of the women with no thoracic fractures still had thoracic hyperkyphosis. The authors conclude that the hyperkyphosis of osteoporotic women is related to anterior compression fractures but also has contributing nonskeletal factors. PMID- 3336729 TI - Precision error in dual-photon absorptiometry related to source age. AB - An average, variable precision error of up to 6% related to source age was observed for dual-photon absorptiometry of the spine in a longitudinal study of bone mineral content involving 393 women. Application of a software correction for source decay compensated for only a portion of this error. The authors conclude that measurement of bone-loss rates using serial dual-photon bone mineral measurements must be interpreted with caution. PMID- 3336730 TI - ACR-NEMA digital imaging and communications standards: minimum requirements. AB - The purposes, implications, and history of development of the American College of Radiology-National Electrical Manufacturers Association (ACR-NEMA) Digital Imaging and Communication Standard and its contents are briefly described, and the minimum requirements of the ACR-NEMA Digital Imaging and Communication Standard are described with a concise introduction of each layer. The usefulness, validity, current status, and future development of the standard are also discussed. PMID- 3336731 TI - Monitoring human tumor response to therapy by means of P-31 MR spectroscopy. AB - Tumors in 23 patients were studied by means of in vivo phosphorus-31 magnetic resonance (MR) spectroscopy. In five patients, the response to chemotherapy and radiation therapy was monitored in a long-term follow-up study. In one patient, the P-31 MR spectra were recorded during the infusion of chemotherapeutic drugs. In comparison with healthy muscle tissue of patients, the tumors showed elevated inorganic phosphate, phosphomonoester, and phosphodiester peaks and reduced creatine phosphate peaks, whereas the nucleoside 5'-triphosphate levels remained nearly unchanged. Tumor treatment resulted in changes in the ratio of the signal intensity value of creatine phosphate to that of inorganic phosphate and in the sum of these values. In an osteosarcoma, an initial response followed by renewed tumor growth was clearly indicated by changes in these parameters. In the short term follow-up examination, slight spectral changes were observed during the infusion of chemotherapeutic drugs. Changes in the concentrations of phosphorus metabolites during therapy can therefore be monitored in human tumors by means of P-31 MR spectroscopy. PMID- 3336733 TI - Selective delivery of chemotherapeutic agents with a new catheter system. AB - A new catheter system was used in ten patients (16 infusions) for infusion of chemotherapeutic agents to the sites of malignant gliomas. Thirteen infusions to the supraophthalmic region were successful, as were three infusions to the posterior cerebral region. There were no complications after the infusions. A neurologic complication occurred in one patient in whom two successful supraophthalmic infusions were previously carried out. In this patient the guide wire separated during catheter placement into the posterior cerebral artery. PMID- 3336732 TI - Plastic-coated guide wire for hepatic arteriography. AB - A guide wire made of a superelastic alloy coated with hydrophilic polymer has been developed for superselective catheterization in hepatic arteriography. In this study, the new wire was tested in 15 patients and a conventional spring wire was used in 25. Catheterization of the proper or more peripheral hepatic arteries was successful in 93.3% of cases in which the new wire was used versus 76.0% in which the conventional spring wire was used. Moreover, the frequency of complications, such as spasm and subintimal injury, was reduced from 28.0% to 6.7%. PMID- 3336734 TI - Simple apparatus to avoid inadvertent needle puncture. AB - Current heightened awareness and concern about accidental needle puncture prompted design of a device to reduce this risk. Holes are made in the top of a prepurchased film cannister; these allow placement of all sharp objects used for angiographic and interventional radiology procedures. This protective cannister is recommended for routine use on all instrument trays, since it lessens the likelihood of inadvertent puncture. PMID- 3336735 TI - Closed system for arterial puncture in patients at risk for AIDS. AB - A method of arterial puncture that makes use of a closed system was developed to reduce the likelihood of contact with blood of patients with acquired immunodeficiency syndrome (AIDS). The system includes a plastic Tuohy-Borst side arm adapter and connecting tubing that are attached to the arterial needle. When the arterial lumen is entered, blood spurts into the connecting tube rather than freely out of the hub of the needle. The guide wire is then advanced through the Tuohy valve into the artery. The technique has been successfully used in 32 patients; no significant complications have been reported. PMID- 3336737 TI - Use of antibiotics in interventional radiologic procedures: an important lesson still to be learned. PMID- 3336736 TI - AIDS awareness in the conduct of radiologic procedures: guidelines to safe practice. AB - The epidemic of the acquired immunodeficiency syndrome (AIDS) has affected all geographic regions of the United States. Indeed, it is likely that a majority of U.S. hospitals have cared for patients who are infected with the human immunodeficiency virus (HIV), the virus that causes AIDS. More than 46,000 individuals with HIV infection have fulfilled the strict diagnostic criteria for AIDS (1). All of these patients with AIDS have been seriously ill and have been hospitalized, often multiple times and for prolonged periods. Another, larger group patients with HIV infection has had another form of the disease, the so called AIDS-related complex. Many of these patients have also spent time in hospitals. An even larger group of individuals has been infected with HIV but has remained asymptomatic to date. Some of these persons have been admitted to hospitals or have received outpatient diagnostic procedures for intercurrent medical or dental complaints that were unrelated to their asymptomatic HIV infection. At the time of their medical evaluation, some of these asymptomatic individuals were known to have a positive HIV antibody test. It is likely, however, that the serologic status of the majority of asymptomatically infected patients was unknown. Thus, by now a very large number of health-care personnel in the United States, including diagnostic radiology staff, have assisted in the care of HIV-infected patients. PMID- 3336738 TI - Antibiotics for radiologic interventional procedures. PMID- 3336740 TI - Experimental investigations of the Hexabrix-papaverine interaction. PMID- 3336739 TI - Validity of dual-photon absorptiometry. PMID- 3336741 TI - Single-versus double-contrast barium studies in elderly patients. PMID- 3336742 TI - Use of contrast media in patients with hypovolemic shock. PMID- 3336743 TI - Hypovolemic shock in children. PMID- 3336744 TI - Meniscal tears: pathologic correlation with MR imaging. PMID- 3336745 TI - Localization grid for MR-guided biopsy. PMID- 3336746 TI - Use of fentanyl and diazepam for special procedures. PMID- 3336748 TI - Which way to go? Your job options. PMID- 3336747 TI - High-resolution MR imaging of abnormal parathyroid glands. PMID- 3336749 TI - Letter and resume: essential first steps. PMID- 3336750 TI - Your next stop: an interviewer's office. PMID- 3336751 TI - Surviving the move into a new job. PMID- 3336752 TI - Going back to school to get ahead. PMID- 3336753 TI - Setting out on your career path. PMID- 3336755 TI - How could I have thought James couldn't be helped? PMID- 3336754 TI - Make the right moves when you respond to a code. PMID- 3336756 TI - Nursing the patient in traction. PMID- 3336758 TI - The very best job a nurse ever had. PMID- 3336757 TI - Can we keep Jane alive until an antidote arrives? PMID- 3336760 TI - Controlling the dangers of epidural analgesia. PMID- 3336759 TI - The nuts and bolts of agency nursing. PMID- 3336761 TI - CAPD: a dialysis breakthrough with its own burdens (continuing education credit). PMID- 3336762 TI - The RN pin collection: where did they come from? PMID- 3336763 TI - Tools for teaching about anticoagulants. PMID- 3336765 TI - The slap that cost a doctor $10,000. PMID- 3336764 TI - Take your assessment all the way down to the toes. PMID- 3336766 TI - Dietary help for PMS patients. PMID- 3336767 TI - The truth about bedpans. PMID- 3336768 TI - What you can do for the depressed caregiver. PMID- 3336769 TI - Guiding parents when a child is on CAPD. PMID- 3336770 TI - Debate rages over breast cancer study. PMID- 3336771 TI - NIH may have to move ASAP on AIDS grants. PMID- 3336772 TI - Zeroing in on the sex switch. PMID- 3336773 TI - Atomic force microscopy of an organic monolayer. AB - Atomic force microscope images of polymerized monolayers of n-(2-aminoethyl) 10,12-tricosadiynamide revealed parallel rows of molecules with a side-by-side spacing of approximately equal to 0.5 nanometer. Forces used for imaging (10(-8) newton) had no observable effect on the polymer strands. These results demonstrate that atomic force microscope images can be obtained for an organic system. PMID- 3336774 TI - Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. AB - Although periodontitis is a bacterial disease, its multidimensional nature and its bacterial complexity have made it difficult to definitively prove that specific microorganisms initiate the disease process. The successful implantation of a rifampin-resistant strain of the putative periodontal pathogen Bacteroides gingivalis into the periodontal microbiota of monkeys (Macaca fascicularis) resulted in an increase in the systemic levels of antibody to the microorganism and rapid and significant bone loss. PMID- 3336775 TI - Human ribosomal RNA genes: orientation of the tandem array and conservation of the 5' end. AB - The multiple copies of the human ribosomal RNA genes (rDNA) are arranged as tandem repeat clusters that map to the middle of the short arms of chromosomes 13, 14, 15, 21, and 22. Concerted evolution of the gene family is thought to be mediated by interchromosomal recombination between rDNA repeat units, but such events would also result in conservation of the sequences distal to the rDNA on these five pairs of chromosomes. To test this possibility, a DNA fragment spanning the junction between rDNA and distal flanking sequence has been cloned and characterized. Restriction maps, sequence data, and gene mapping studies demonstrate that (i) the rRNA genes are transcribed in a telomere-to-centromere direction, (ii) the 5' end of the cluster and the adjacent non-rDNA sequences are conserved on the five pairs of chromosomes, and (iii) the 5' end of the cluster is positioned about 3.7 kb upstream from the transcription initiation site of the first repeat unit. The data support a model of concerted evolution by interchromosomal recombination. PMID- 3336776 TI - Risk of human immunodeficiency virus (HIV-1) infection among laboratory workers. AB - In a prospective cohort study of 265 laboratory and affiliated workers, one individual with no recognized risk factors for human immunodeficiency virus type 1 (HIV-1) infection was HIV-1 seropositive at the time of entry into the study. Molecular analyses of two HIV-1 isolates derived in two independent laboratories from a blood sample from this worker showed that the isolates were indistinguishable from a genotypic form of HIV-1 present in the H9/HTLV-IIIB cell line. Exposure to this strain of virus most probably occurred during work with concentrated virus or culture fluids from virus-producing cell lines under standard Biosafety Level 3 containment. Although no specific incident leading to this infection has been identified, undetected skin contact with virus culture supernatant might have occurred. This worker was the only one found to be positive among the subgroup of 99 workers who shared a work environment involving exposure to concentrated virus. The incidence rate of 0.48 per 100 person-years exposure indicates that prolonged laboratory exposure to concentrated virus is associated with some risk of HIV-1 infection, which is comparable to the risk for health care workers experiencing a needle stick exposure. While none of the ten workers with parenteral exposure to HIV-1 in this cohort became infected, a worker in another laboratory did seroconvert following an injury with a potentially contaminated needle. Strict Biosafety Level 3 containment and practices should be followed when working with concentrated HIV-1 preparations, and further refinement of the procedures may be necessary. PMID- 3336777 TI - A new threat to world health. PMID- 3336778 TI - AIDS funds increased; Helms measure blunted. PMID- 3336779 TI - Neurometrics: computer-assisted differential diagnosis of brain dysfunctions. AB - Normative developmental equations provide reliable descriptors of brain electrical activity in people 6 to 90 years old. Healthy persons display only chance deviations beyond predicted ranges. Patients with neurological impairment, subtle cognitive dysfunctions, or psychiatric disorders (including dementia and primary depression) show a high incidence of abnormal values. The magnitude of the deviations increases with clinical severity. Different disorders are characterized by distinctive profiles of abnormal values of brain electrical features. Computerized differential classification of some of these disorders can be achieved with high accuracy. Such classification, providing objective corroboration of brain dysfunctions, may be a useful adjunct to psychiatric diagnosis, which relies primarily on subjective clinical impressions. These methods may provide independent criteria for diagnostic validity, evaluations of treatment efficacy, and more individualized therapy. PMID- 3336780 TI - Cell wall is required for fixation of the embryonic axis in Fucus zygotes. AB - Establishment of a primary developmental axis generally is thought to involve rearrangements in the plasma membrane or cytoplasm of the egg. In this report the additional requirement for cell wall in polarization of Fucus zygotes was investigated. Protoplasts of fertilized eggs were tested for their ability to establish an axis in accordance with an orienting vector of unilateral light. The results demonstrate that cell wall is not required for axis formation. However, the orientation of the axis remains labile until new cell wall is synthesized. The presence of a cell wall is an absolute requirement for axis fixation. PMID- 3336782 TI - Animals in the lab. PMID- 3336781 TI - Transmission of HIV in Belle Glade, Florida: lessons for other communities in the United States. AB - The high cumulative incidence of AIDS and the large percentage of AIDS patients with no identified risks in Belle Glade, Florida, were evaluated through case interviews and neighborhood-based seroepidemiologic studies. It was found that of 93 AIDS patients reported between July 1982 and 1 August 1987, 34 could be directly linked to at least one other AIDS patient or to a person with AIDS related complex by sexual contact, sharing of needles during intravenous drug abuse (or both), or perinatal exposure; of 877 randomly selected adults, 28 had antibodies to HIV; no person over age 60 and none of 138 children aged 2 to 10 years had antibodies to HIV; no clustering of infected persons within households occurred, except in sex partners; and HIV-seropositive adults were more likely than HIV-seronegative adults to be from Haiti, have a lower income, report sex with intravenous drug abusers, and have a history of previous treatment for sexually transmitted diseases. The presence of antibodies to five arboviruses prevalent in South Florida or the Caribbean did not correlate significantly with HIV infection. The high cumulative rate of AIDS in Belle Glade appears to be the result of HIV transmission through sexual contact and intravenous drug abuse; the evidence does not suggest transmission of HIV through insects. PMID- 3336783 TI - Radon's health risks. PMID- 3336785 TI - U.S.-Japan cooperation. PMID- 3336784 TI - DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. AB - By means of a selective DNA amplification technique called polymerase chain reaction, proviral sequences of the human immunodeficiency virus (HIV-1) were identified directly in DNA isolated from peripheral blood mononuclear cells (PBMCs) of persons seropositive but not in DNA isolated from PBMCs of persons seronegative for the virus. Primer pairs from multiple regions of the HIV-1 genome were used to achieve maximum sensitivity of provirus detection. HIV-1 sequences were detected in 100% of DNA specimens from seropositive, homosexual men from whom the virus was isolated by coculture, but in none of the DNA specimens from a control group of seronegative, virus culture-negative persons. However, HIV-1 sequences were detected in 64% of DNA specimens from seropositive, virus culture-negative homosexual men. This method of DNA amplification made it possible to obtain results within 3 days, whereas virus isolation takes up to 3 to 4 weeks. The method may therefore be used to complement or replace virus isolation as a routine means of determining HIV-1 infection. PMID- 3336786 TI - Fat survey trimmed in lean budget. PMID- 3336787 TI - AIDS virus creates lab risk. PMID- 3336788 TI - Gene identity confirmed. PMID- 3336789 TI - A parent's sex may affect gene expression. PMID- 3336790 TI - Epithelial tumors of the ovary in women less than 40 years old. AB - From Jan 1, 1978 through Dec 31, 1983, 64 patients with epithelial ovarian tumors, frankly malignant or borderline, were managed at one institution. Nineteen patients (29.7%) were under age 40. The youngest patient was 19 years old. Nulliparity was present in 32% of this group of patients. Of these young patients, 58% had borderline epithelial tumors, compared to 13% of patients over 40 years of age. Twenty-one percent of the young patients were initially managed by unilateral adnexal surgery. The overall cumulative actuarial survival rate of all young patients was 93%. Young patients with epithelial ovarian tumors tend to have earlier grades of epithelial neoplasms, and survival is better than that reported for older patients with similar tumors. PMID- 3336791 TI - Drechslera, not Dreschlera. PMID- 3336792 TI - Optometric Practice Act. PMID- 3336793 TI - Thyrotoxicosis and seizures. PMID- 3336794 TI - Cervical cerclage: a ten-year review in a large hospital. AB - This retrospective study of 129 pregnancies treated with cervical cerclage was done to analyze differences, if any, in reproductive outcome according to gestational age, race, history of previous successful pregnancy, gravidity, and procedure used (McDonald vs Shirodkar cerclage). Fetal salvage was significantly improved only when cerclage was done before 18 weeks of gestation. Cervical cerclage between 18 and 26 weeks' gestation significantly increased the prematurity rate. Cervical cerclage significantly improved fetal salvage in both the black and white populations but at the expense of increasing the prematurity rate in the former. There was no difference in fetal salvage whether the patient had had a previous successful pregnancy or not, or whether the patient was a primigravida or multigravida. Fetal salvage was significantly improved with both the McDonald and Shirodkar procedures, with no significant differences in the complication, prematurity, or cesarean section rates. PMID- 3336795 TI - Nipple discharge: surgical significance. AB - Nipple discharge is an important clinical entity ranking second only to a lump as the most common complaint among 7,588 patients having breast surgery (560/7,588, or 7.4%). In the office and clinic it is even more common, since many patients can be treated medically and do not require an operation. To be significant, a discharge should be true, spontaneous, persistent, and nonlactational. Nipple discharge can be milky, multicolored and sticky, purulent, clear (watery), yellow (serous), pink (serosanguineous), or bloody (sanguineous). Watery, serous, serosanguineous, and sanguineous discharges are surgically significant; while they are most often caused by intraductal papillomas or fibrocystic disease, they can be due to cancer or a precancerous mastopathy. Among 503 patients operated on for one of these types of discharge, 67 (13.3%) had cancer, and 36 (7.2%) had a precancerous mastopathy. Among the 67 patients with cancer, eight (11.9%) had no palpable mass, 11 (16.4%) had negative cytologic findings, and seven (10.4%) had a negative mammogram. The incidence of associated cancers increases when the discharge is, in order of increasing frequency, serous, serosanguineous, sanguineous, or watery, when it is accompanied by a lump, when it is unilateral and from a single duct, when there are positive cytologic or mammographic findings, and when the patient is more than 50 years of age. Milky discharge caused by galactorrhea is treated medically except when caused by a pituitary adenoma. Multicolored sticky discharge due to duct ectasia is also treated medically except in advanced cases. Purulent discharge caused by an abscess requires drainage and a biopsy of the abscess wall. Except in women less than 30 years of age of in those anxious to have children, we advise a complete central duct excision for patients with surgically significant types of discharge. If done carefully, this procedure can yield good cosmetic results. PMID- 3336796 TI - Bilateral pelvic lymphadenectomy, iridium 192 template, and external beam therapy for localized prostatic carcinoma: complications and results. AB - Thirty-five patients with prostatic adenocarcinoma were treated by bilateral pelvic lymphadenectomy and temporary implantation of iridium 192 strands with adjuvant external beam radiotherapy. With the implant the prostate received between 3,200 and 3,500 gray (Gy) followed in two weeks by small-field external beam irradiation for an additional dose of approximately 3,400 Gy. Morbidity included an ileofemoral thrombosis in one patient, and transient radiation proctitis in four patients; one patient required transurethral prostatic resection for obstruction at one year. Local response of the primary tumor was dramatic in every case at three-month follow-up. In 11 of 15 patients (73%), biopsy at one year showed no evidence of disease. PMID- 3336797 TI - Repair of aneurysms of the thoracic aorta: 12-year experience in a high-risk population. AB - We present our 12-year experience with surgical treatment of aneurysms of the thoracic aorta in a high-risk patient population. Of 52 patients with aneurysms, 36 patients, aged 19 to 80 years, had operation. In 24 of the 36, there were three or more associated major disease processes, such as chronic bronchitis, hypertensive cardiovascular disease, aortic valve disease, cerebrovascular disease, abdominal aortic aneurysm, and coronary artery disease. Eight patients with acute type A (ascending aorta) and seven with acute type B (descending aorta) aneurysms had emergency repair, with survival in four and seven, respectively. All patients with chronic type A or B aneurysms had elective repair, and all patients with acute or chronic type A aneurysms had surgical treatment. Four patients with acute type A and two with acute type B aneurysms had elective operation, with survival in three and one, respectively. Nine patients with chronic type A and six with chronic type B aneurysms had elective operation, and all survived. Twelve patients with chronic type B aneurysms did not have operation, and all were alive at early follow-up. Mortality for patients having acute type A aneurysms requiring emergency operation was greater than that after elective repair of acute or chronic type A aneurysms. Short-term survival for chronic type B aneurysms was similar whether the patient was treated medically or surgically. PMID- 3336798 TI - Delayed diagnosis in pediatric appendicitis. AB - Delay in appendectomy occurs from failure to contact a physician, or from a physician's failure to make a proper diagnosis. In our study delay was due to physician error in 32 of 422 children who had appendectomy. Symptoms consistent with appendicitis were documented on the initial visit in each case, but 22 patients had a history of previous similar pain or recent viral illness to confuse the diagnosis. Misdiagnosis was responsible for the delay in 14 cases (gastroenteritis in ten and urinary tract infection in four). Antibiotics given before proper diagnosis in 22 instances increased diagnostic difficulty in 20. Late referral is increasing, perhaps because of a perceived innocuous nature of appendicitis. Complicated appendicitis was found in 26 children (81%), compared with 38% of the total experience. Their hospital stay averaged nine days, as opposed to 6.6 days in the nondelayed group. Failure of resolution of symptoms after therapy begins mandates reassessment to avoid progression of this common surgical disease. PMID- 3336799 TI - Victim factor correlates of traumatic infant death in South Carolina. AB - In South Carolina over a nine-year period, the adjusted odds that infants who died of injuries had been of low birth weight were 2.65:1 as compared to a live born control group. The odds that injury victims were black were 1.84:1 as compared to control subjects. For victims of accidents only, the odds ratio for low birth weight was 2.37, and for black race, 1.61. For victims of homicide, the odds ratio for low birth weight was 6.15, and for black race, 4.76. Male sex, high birth order, low Apgar score, and the presence of a congenital anomaly were not significant infant risk factors by multifactorial analyses. PMID- 3336800 TI - Extracorporeal shock wave lithotripsy: review of the first 100 cases at the Kidney Stone Center of Southeast Georgia. AB - We reviewed the first 100 consecutive patients treated with extracorporeal shock wave lithotripsy (ESWL) at one institution. A total of 115 treatments were delivered to 58 men and 42 women. Patients with calculi of various sizes were treated and compared for (1) length of hospitalization, (2) ancillary procedures, (3) repeat ESWL, (4) obstructive complications, (5) parenteral analgesic requirements, and (6) stone-free rate. Patients were grouped according to calculus length. Group A consisted of 76 patients with calculi totaling less than 3 cm. Group B contained 24 patients with calculi totaling more than 3 cm. In group A, 96% required a single ESWL procedure. Hospitalization averaged two days, and none had obstructive complications; 33% required no parenteral analgesics. In group B, 58% received a single ESWL treatment, whereas 88% required ancillary procedures. Results showed extracorporeal shock wave lithotripsy to be effective treatment of urinary calculi measuring less than 3 cm. Larger calculi required combinations of ESWL with other endourologic treatment. PMID- 3336801 TI - Melanoma with metastasis to regional axillary or inguinal lymph nodes: prognostic factors and results of surgical treatment in 714 patients. AB - In a retrospective analysis of 714 patients with melanoma who had node dissection for histologically positive regional axillary or inguinal node metastases at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston during a 30-year interval (1944 to 1974), with a minimum of ten years of follow-up, we determined that the major prognostic factor of survival was the number of positive nodes. Other prognostic variables independent for the number of positive nodes were the favorable survival in patients with primary melanoma on the calf, and the adverse survival effect of extranodal melanoma at node dissection or recurrent metastases within the node dissection region. Factors that did not predict survival after the development of regional node disease were the age, sex, and race of the patient; location of the primary melanoma other than calf; immediate versus delayed node dissection; adjuvant treatment after node dissection; and the development of regional in-transit cutaneous metastases. Metastasis to regional nodes as a harbinger of disseminated disease was reflected in the 33% five-year and 28% ten-year survivals calculated from the date of node dissection. PMID- 3336802 TI - Pathologic fractures of the humerus. AB - In a study of 57 actual or impending pathologic fractures of the humerus in 52 patients with inoperable cancer treated between 1972 and 1982, we retrospectively reviewed the charts for analysis and comparison of the functional result and pain relief afforded by the various treatments used. Function of the extremity and relief of pain were each graded as excellent, good, fair, or poor using a modification of Perez's rating system. Seven pathologic fractures were treated nonoperatively. These patients generally had only fair pain relief and a poor functional result. Forty-six pathologic fractures were treated with intramedullary fixation using a Rush rod (n = 16), a Kuntscher rod (n = 29), or an Ender rod (n = 1); the Neer endoprosthesis was used in four patients. Thirty one patients received radiation to the humerus. There were seven operative complications, the most common (n = 3) being prominence of an intramedullary rod at the insertion site which required a second minor procedure for advancement of the rod. From this series, we conclude that any patient who has a pathologic fracture or impending fracture of the humerus and a predicted survival of six weeks or more is likely to benefit from rigid internal fixation with an appropriately selected device, adjunctive use of methylmethacrylate, and postoperative local irradiation therapy as needed. PMID- 3336803 TI - Reducing the serum cholesterol level with a diet high in animal fat. AB - Multiple food allergies required a group of seven patients with elevated serum cholesterol levels to follow a diet in which most of the calories came from beef fat. Their diets contained no sucrose, milk, or grains. They were given nutritional supplements. This is the only group of people in recent times to follow such a diet. During the study, the patients' triglyceride levels decreased from an average of 113 mg/dl to an average of 74 mg/dl; at the same time, their serum cholesterol levels fell from an average of 263 mg/dl to an average of 189 mg/dl. At the beginning of the study, six of the patients had an average high density lipoprotein percentage of 21%. At the end of the study, the average had risen to 32%. These findings raise an interesting question: are elevated serum cholesterol levels caused in part not by eating animal fat (an extremely "old food"), but by some factor in grains, sucrose, or milk ("new foods") that interferes with cholesterol metabolism? PMID- 3336804 TI - Elevated platelet-surface-bound IgM in thrombotic thrombocytopenic purpura. AB - The level of platelet-surface-bound IgM (PSIgM) was measured during the course of therapy in two patients with thrombotic thrombocytopenic purpura (TTP). Before therapy, both had significantly elevated PSIgM. In both cases the PSIgM dropped after the institution of treatment with plasmapheresis, steroids, and dipyridamole, correlating with a complete response to therapy in one patient and a partial response in the second. This is further evidence that in some cases of TTP, an immune mechanism is present. PMID- 3336805 TI - Diaphragmatic pain in pulmonary endometriosis. AB - The diagnosis of pulmonary endometriosis is difficult and requires a high index of suspicion in patients with pelvic endometriosis. We have reported a case in which a history of periscapular pain associated with menses proved useful in delineating the cause of the hemothorax. PMID- 3336806 TI - Adrenal myelolipoma: rationale for nonoperative management. AB - With increasing use of computerized tomography and ultrasonography, asymptomatic lesions of the adrenal gland are frequently detected. One such tumor is the adrenal myelolipoma, composed of adipose and hemic elements histologically resembling bone marrow. This tumor can be diagnosed by its characteristic appearance on CT scan, and fine-needle biopsy guided by CT can be used to obtain a tissue diagnosis. Because patients with adrenal myelolipoma typically have recurrence of symptoms after resection, surgical intervention is not indicated unless an enlarging tumor impinges on surrounding structures. PMID- 3336807 TI - Toxoplasmosis associated with nephrotic syndrome in an adult. AB - Symptomatic generalized toxoplasmosis is uncommon in an immunocompetent host. Even more unusual is the association of nephrotic syndrome with toxoplasmosis, which has previously been reported only in congenital or pediatric cases. This is the first reported case of generalized toxoplasmosis with nephrotic syndrome in an immunocompetent adult. This case should serve to alert the clinician to the possibility of toxoplasmosis in the diagnosis of FUO and adult nephrotic syndrome, and it demonstrates resolution without antimicrobial agents. PMID- 3336808 TI - Obstruction of defunctionalized loop ten years after jejunoileal bypass for morbid obesity. AB - We have reported a case of obstruction due to volvulus of the ileosigmoid anastomosis ten years after jejunoileal bypass. Revision of the ileosigmoid anastomosis with drainage of the defunctionalized limb into the cecum relieved the obstruction. PMID- 3336809 TI - Hot flash epilepsy. AB - A woman had episodes of bilateral thermal sensation, initially thought to be hot flashes related to menopause. EEG telemetry documented the epileptic nature of the attacks with an electrographic seizure emanating from the right temporal area coincident with the hot flashes. PMID- 3336810 TI - Amputation level and distal bypass salvage of the limb. AB - The feasibility of revascularization of the lower extremity for salvage of the limb with grafts to the tibial and peroneal arteries has been well established. The results of prior reports have suggested that a failed distal bypass may convert a lower extremity amputation to a higher level than afforded by primary amputation. We reviewed all distal, tibial or peroneal artery bypasses performed at our institution during the period of March 1980 through October 1986. Fifty three patients with 59 threatened lower extremities underwent distal bypass for salvage of the limb. No patient was excluded from review. Thirty-eight patients in the study group had diabetes, and 41 had a prior smoking history. In the postoperative period, six patients were lost to follow-up study, nine patients died, with follow-up data complete in 47 of the study group. The maximum length of follow-up study was 78 months, and the average length was 24 months. Data were examined by life table analysis with respect to cumulative salvage of the limb and graft patency. During the period of review, 12 major amputations were required (nine below-knee and three above-knee) for a cumulative salvage rate of 59 per cent. Of the distal grafts which failed (n = 27), three of 27 of the limbs required above-knee amputation. We conclude that a failed tibial or peroneal artery bypass does not preclude the possibility of salvage of the limb and does not predispose to a subsequent amputation. PMID- 3336811 TI - Interaction of neurotensin, secretin and cholecystokinin on pancreatic exocrine secretion in conscious dogs. AB - The results of previous studies from our laboratory have shown that neurotensin can stimulate pancreatic secretion of bicarbonate and protein. This study was done to compare the stimulatory action of neurotensin on pancreatic exocrine secretion in conscious dogs to those of secretin and cholecystokinin (CCK). Six dogs with chronic pancreatic and gastric fistulas were given hydrochloric acid intraduodenally or CCK-8 intravenously to produce maximal bicarbonate or protein secretion. Neurotensin was then given intravenously in combination with intraduodenal hydrochloric acid or intravenous CCK-8. Incremental bicarbonate outputs in response to intraduodenal hydrochloric acid alone were measured and compared with intraduodenal hydrochloric acid plus intravenous neurotensin. Intravenous administration of neurotensin augmented pancreatic bicarbonate and protein secretory responses to a maximal dose of intraduodenal hydrochloric acid. Incremental protein responses to intravenous CCK-8 alone were measured and compared to intravenous CCK-8 plus intravenous neurotensin. Incremental bicarbonate responses to intravenous CCK-8 alone were compared with intravenous CCK-8 plus intravenous neurotensin. Similarly, intravenous neurotensin augmented pancreatic protein and bicarbonate secretory responses to a maximal dose of intravenous CCK-8. The results of this study indicate that neurotensin may stimulate pancreatic secretion of protein and bicarbonate by mechanisms which are different from those of CCK and secretin. Neurotensin apparently exerts its action through specific neurotensin receptors. PMID- 3336812 TI - Extended patency of expanded polytetrafluoroethylene grafts for vascular access using optimal configuration and revisions. AB - During a seven year period, 189 expanded polytetrafluoroethylene (PTFE) grafts for vascular access were implanted in 131 patients with end stage renal disease requiring long term hemodialysis. Over-all cumulative patency rate for all grafts was 76 per cent at 12 months, 50 per cent at 36 months and 40 per cent at 60 months. Forearm grafts of loop configuration yielded greater over-all patency rates and required fewer revisions than forearm grafts of straight configuration. Graft thrombosis was the universal indicator of graft malfunction. In the instance of a malfunction, immediate thrombectomy followed by angiography was considered essential to decisions regarding further therapy. Of 95 grafts that malfunctioned, 49 ultimately required revision, extending the survival to a rate equaling that of continuously functioning grafts. Extensive venous stenosis limiting outflow and multiple intragraft stenosis were the main causes of graft failure. For patients in whom all vessels of the upper extremity had been exhausted, thigh grafts of the loop configuration and axilloaxillary grafts proved to be satisfactory alternatives. Although PTFE grafts are not the final solution for vascular access in hemodialysis, in many instances, they will serve well, provided the surgeon gives proper consideration to their most efficacious use. PMID- 3336813 TI - An angiographic study of ischemia as a determinant of neovascularization in arteriovenous reversal. AB - The results of recent studies by ourselves and others have demonstrated the feasibility of revascularizing severely ischemic limbs by means of staged arteriovenous reversal at the popliteal level. The results of investigations we did, both clinically and in an animal model, revealed the development of an intense vascular network in the region of the arteriovenous anastomosis as an important component of the revascularization process. To determine the role of ischemia in this process, four groups consisting of three dogs each underwent a popliteal artery to vein anastomosis. In group I, there was no ischemia; group II, distal ischemia only; group III, partial ischemia, and group IV, total ischemia. Angiography at four weeks in all dogs demonstrated that the intense neovascular network seen in previous studies developed only in the limbs of the dogs in group IV. We conclude that the neovascular process seen after creation of arteriovenous reversal develops as a response to severe ischemia. Further studies are needed to better characterize the nature of these vessels, and it is our hope that, in doing so, means of enhancing development of these vessels in order to indirectly revascularize otherwise unsalvagable extremities will be realized. PMID- 3336814 TI - Anal canal pressure and motility after ileoanal anastomosis. AB - This study was done to determine the effect of mucosal rectectomy and ileal pouch to anal anastomosis (IAA) on pressure and motility of the anal canal. Fifty patients, 22 +/- 2 months after operation (mean plus or minus standard error of the mean), and 30 healthy control volunteers were studied. Twenty-eight patients had excellent continence, while 22 had episodic minor incontinence. The maximum resting pressure in the anal canal was reduced in patients with episodic incontinence compared with continent patients and control volunteers. The increase in pressure with squeeze was slightly greater in continent than in incontinent patients. The frequency of the anal slow waves was less after IAA than in control volunteers and the amplitude of the waves was greater. The frequency and amplitude, however, were not related to continence or resting pressure. In conclusion, decreased anal canal resting and squeeze pressures after ileal pouch to anal anastomosis are associated with episodic minor incontinence, while altered motility patterns in the anal canal are not. PMID- 3336815 TI - The changing patterns of occurrence and management in primary mediastinal tumors and cysts in the People's Republic of China. AB - Primary mediastinal tumors and cysts (MTC) constitute a common problem in thoracic operations done in the People's Republic of China. Data from 4,357 instances of MTC diagnosed in China between 1963 and 1985, including 307 from our own facility, are presented. Teratoid tumors are the most common of the MTC in the northern part of China contrasting with thymomas and neurogenic tumors which are the most common in the southern part of China; a finding that notes a significant difference (p less than 0.01). Beyond this, the distribution of MTC is different than in North America. In patients we studied, we were able to predict the correct histopathologic diagnosis 80 per cent of the time by considering the history of the patient and the results of a conventional roentgenogram of the chest. This was increased to 91.4 per cent when needle biopsy was added. Optimal therapy for MTC is complete surgical resection. We present a scheme for localization of the various types of MTC and an operative approach. PMID- 3336816 TI - The lateral approach to the above-knee femoropopliteal bypass. AB - Functional salvage of the limb was successful in a patient using a lateral approach to the above-knee femoropopliteal bypass. An expanded polytetrafluoroethylene prosthesis was placed in a lateral subcutaneous tunnel. This new technique offers a direct and practical alternative to the classic approaches to the proximal part of the popliteal artery and may be useful when previous scarring, infection or unusual circumstances precludes their use. PMID- 3336817 TI - An alternative to Roux-en-Y for treatment of bile reflux gastritis. AB - Exclusion jejunoduodenostomy has been successfully used as the primary operation in five patients with severe bile reflux gastritis and in one patient with disabling Roux-en-Y syndrome. The operation is simple to perform, requires one anastomosis and appears to eliminate bile reflux gastritis and avoid potential emptying complications associated with the Roux-en-Y segment. PMID- 3336818 TI - Large disposable trephines for circular excision biopsy of the skin. AB - Large disposable circular trephines have been developed specially for circular excision biopsy of the skin. This technique is a simple and practical alternative to the traditional method of excision. It has the advantages of aligning the incision in the direction of the maximum skin tensions and reducing the length of the final wound closure. PMID- 3336819 TI - The use of the biliary Fogarty catheter as an aid in sphincterotomy. PMID- 3336821 TI - A double ballooned inflatable and collapsible T tube for selective proximal or distal cholangiography. AB - A double ballooned T tube for common bile duct occlusion and optional collapse of the intra-balloon tube segments was used for improved roentgenologic delineation of the biliary tree intraoperatively and postoperatively. This silicone T tube is effective for intraoperative and completion cholangiograms, and avoids resuturing of the choledocotomy. Furthermore, with increased inflation, each balloon is capable of occluding the proximal or distal, or both, intraductal horizontal limbs. These features have been exploited for optimal imaging and therapeutic purposes. The tube with its deflated balloons is left in the common duct for drainage and further selective proximal or distal cholangiograms. Several extensions of its use can be envisaged. PMID- 3336820 TI - A simple and direct approach to the portal triad structures for a left lobectomy or a left lateral segmentectomy. AB - The hilar isolation and dissection of portal pedicle is usually performed prior to hepatectomy in order to minimize blood loss intraoperatively. In some instances, it is difficult to visualize and encircle the bifurcation of the portal triad structures. We recommend the use of a simple and safe method of direct approach to the transverse portion of the portal vein in the left lobectomy or lateral segmentectomy, by incision and dissection of the ligament teres hepatis and continuing fatty tissue. PMID- 3336822 TI - An aid to axillary dissection. AB - Abduction facilitates axillary dissection. Full abduction with the hand behind the head permits maximal operative exposure. This is due to the posterior axillary wall passing anteriorly and displacing the axillary contents into a superficial position. This movement is demonstrated roentgenographically. PMID- 3336823 TI - Management of urolithiasis during pregnancy. AB - Renal calculus disease is an infrequent, but not insignificant, occurrence during pregnancy. Fortunately, the majority of symptomatic calculi that present during pregnancy pass spontaneously. However, 20 to 30 per cent of patients do require intervention for stones, posing a diagnostic and therapeutic challenge. Delay in treatment may jeopardize the pregnancy. Traditional methods of intervention for renal calculus disease have been supplanted by advanced, less invasive techniques; however, their application for the pregnant patient has not been addressed adequately. The varied presentation of urolithiasis during gestation and the use of newer methods of treatment in each is discussed. PMID- 3336824 TI - Anatomic and functional results of surgical repair after total perineal rupture at delivery. AB - Laceration of the perineum during delivery might sever the anal sphincter and result in discomfort, pain and even anal incontinence. We reviewed the degree of incontinence after repair of the anal sphincter in 20 female patients with complete third degree lacerations after delivery. In addition, anal manometry was performed upon seven patients. The resting and squeeze pressures were measured. At the same time, single needle electromyography of the external sphincter muscle was recorded. An uneventful recovery was found in all patients. This was confirmed by restoration of the anal pressures of voluntary and involuntary control within low to low normal limits indicating an almost complete anatomic recovery of the anal sphincter complex. Three patients had complaints of incontinence. These complaints were often neglected by both the obstetrician and patient. In these patients, anal manometric measurements together with single needle electromyography of the external anal sphincter muscle were not useful diagnostic methods for determining anal incontinence. PMID- 3336825 TI - Hepatic hemodynamics after chronic obstruction of the biliary tract in the dog. AB - Hepatic blood flow was measured in 12 dogs before and two weeks after obstruction of the bile duct (BD) or sham operation, using the electromagnetic flowmeter technique. Eight dogs with obstructed BD revealed an 41 per cent decrease in total hepatic blood flow caused by an approximately equal percentage decrease in both hepatic arterial (HA) and portal venous (PV) flow, a decrease in arterial blood pressure, an increase in PV vascular resistance and little change in hepatic oxygen consumption. Four sham operated dogs showed minimal hemodynamic response. A dual mechanism for the hepatic hemodynamic consequences of chronic biliary obstruction is suggested: Decreased HA blood flow associated with diminished blood pressure and reduced PV blood flow resulting from raised intrahepatic PV vascular resistance. PMID- 3336826 TI - Duodenogastrocolic reflux after colonic interposition measurement using scintigraphic method. AB - Enterogastric reflux was studied using the scintigraphic method in 20 patients with colonic interposition for benign esophageal disease. The state of the transplanted colonic mucosa was evaluated by endoscopy. In 16 patients, reflux of the duodenal contents into the stomach could be seen. In eight, reflux of the duodenal contents into the interposed colon could be demonstrated. There were no differences in the occurrence of reflux into the colonic graft between the isoperistaltic and antiperistaltic interpositions. In three patients, signs of colitis on the mucosa on the lower part of the graft were observed by endoscopy. Each of these patients had a reflux of the duodenal contents into the colonic graft. In monitoring the 24 hour pH of these three patients, one patient had marked acid reflux. Alkaline reflux was not observed. It is concluded that enterogastric reflux is frequent in patients with colonic interposition. Its role in the development of lower colonic graft colitis changes is discussed. PMID- 3336827 TI - Placement of Hickman-Broviac catheters in the cephalic vein. AB - By approaching the cephalic vein with an incision placed high in the deltopectoral triangle, instances in which the cephalic vein is absent or too small to cannulate will almost always result in the successful cannulation of an alternative vein located in this region. In those rare instances in which there is no vein which can be cannulated on one side, contralateral dissection is likely to be successful. Occasionally, a catheter will be seen to pass over the clavicle into the external jugular vein. The catheter should be withdrawn and rethreaded because repeat attempts at central placement will usually be successful. PMID- 3336828 TI - Pancreatic pseudocystojejunostomy without Braun or Roux-en-Y anastomosis. PMID- 3336829 TI - Inferior gluteal musculocutaneous flap for the obliteration of acute and chronic proctocolectomy defects. PMID- 3336830 TI - A new technique for closed thoracostomy insertion of chest tube. AB - A new technique for percutaneous closed thoracostomy insertion of a chest tube is now available. It appears to be a more comfortable one for the operator and the patient. With widespread use, it is expected to improve the effectiveness and reduce the morbidity and mortality rates resulting from chest tube insertions. PMID- 3336831 TI - Absorbable staples in abdominal hysterectomy. AB - A technique is illustrated wherein the vaginal vault is closed with absorbable staples before the cervix is excised. The resulting minimal contamination of the pelvis and small avascular pedicles improves the postoperative course of the patient. PMID- 3336832 TI - Coaxial needle biopsy of lesions of the lung guided by computed tomography. AB - Thirty patients underwent coaxial needle aspiration biopsies of lesions of the lung under CTG. Tissue obtained was adequate for diagnosis in 90 per cent of the patients. The incidence of pneumothorax was low using the coaxial needle technique. The limitations of the fine needle are diminished, and the risk of tumor implant during the procedure is greatly minimized. Additional studies should be conducted to further evaluate this technique and confirm its safety. PMID- 3336833 TI - The use of a stapler in splenic salvage as an alternative to the sutured partial splenectomy or splenorrhaphy. PMID- 3336835 TI - Acute subdural hematoma due to minor head trauma in patients with a lumboperitoneal shunt. AB - The cases of four patients treated with a lumboperitoneal shunt in whom acute subdural hematoma occurred after minor head trauma are presented. Three of the four patients had subdural fluid collection or widening of subarachnoid space observed on computed tomography scan after placement of the lumboperitoneal shunt. We report that patients with a lumboperitoneal shunt have the potential to develop acute subdural hematoma due to minor head trauma, and discuss its mechanism. PMID- 3336834 TI - Acute diverticulitis of the cecum and ascending colon diagnosed by computed tomography. AB - Between June 1984 and August 1985, computed tomography (CT) was performed upon seven patients with diverticulitis of the cecum and ascending colon who presented with acute right lower quadrant symptoms of unknown origin. Three of these patients had undergone an appendectomy, while in the remaining four patients, the history and physical findings were atypical of acute appendicitis. CT findings suggestive of acute diverticulitis including thickening of the intestinal wall and pericolonic inflammation were present in all seven patients. In four patients, the colonic inflammation was limited to the segment of ascending colon superior to the ileocecal valve. In one patient, the inflammation involved both the ascending colon and the cecum, while in the two remaining patients, the inflammatory changes were limited to the cecum. An associated diverticular abscess was present in five patients and all were correctly identified preoperatively by CT. One patient in whom the diagnosis of uncomplicated diverticulitis of the ascending colon was made on the basis of the CT scan, was successfully managed nonoperatively with antibiotics. Five patients required a right hemicolectomy for perforated diverticulitis with abscess. The remaining patient underwent a right hemicolectomy for recurrent episodes of acute diverticulitis. Our experience suggests that CT is useful in the early diagnosis of diverticulitis of the cecum and ascending colon. PMID- 3336837 TI - Multiple cavernous hemangiomas of the orbits. AB - Intraocular tumors were detected in both orbits simultaneously by computed tomography scanning in a 45-year-old woman complaining of proptosis of the right eye, decreased visual acuity, and diplopia. The tumor in the right orbit was resected by the subfrontal extradural approach, and that in the left orbit by the Kronlein-Berke method. The right tumor was found on the side of the external ear of the muscle cone and the left tumor was located inferiorly on the side of the external ear of the muscle cone. Both tumors were cavernous hemangiomas with identical macroscopic and histologic features. PMID- 3336836 TI - Bilateral intracranial fibrous xanthoma. AB - We present a case of fibrous xanthoma in a 6-year-old boy who showed disturbance of consciousness and signs of increased intracranial pressure. A computed tomographic (CT) scan showed bitemporal enhanced masses and hydrocephalus. The patient was operated on in two stages. The tumors were located intradurally and extracerebrally and were firmly attached to the dura mater at the base of the middle fossa. Glial fibrillary acidic protein stain was negative, and histologic examination suggested a diagnosis of bilateral fibrous xanthoma. Postoperative CT scan showed residual tumors and an enlarged choroid plexus adjacent to it. A CT scan at 12 years of age showed no enhanced tumor, but disclosed bitemporal high density areas and diffuse brain atrophy; the choroid plexus reverted to normal size. The patient showed mental and physical retardation, perhaps owing to the compression of the hypothalamus during early childhood. This would appear to be the first known case of bilateral intracranial fibrous xanthoma. PMID- 3336838 TI - Bilateral giant intracavernous aneurysms. Technique of unilateral operation. AB - We report a case of bilateral intracavernous giant aneurysms of which the right side was clipped by direct surgery. Our case was a 74-year-old woman who developed bilateral abducens palsy. Computed tomography and angiography showed bilateral intracavernous giant aneurysms. This patient was followed up in the outpatient clinic. She developed headache and right trigeminal neuralgia 2 years later. The trigeminal pain was quite severe and very disturbing to her. Repeat angiography showed an increase in the size of the aneurysms. An operation was carried out after a balloon Matus test monitoring electroencephalogram, somatosensory evoked potential, and clinical symptoms. The cavernous sinus was opened and the aneurysm was clipped. There was no postoperative complication except right ophthalmoplegia which resolved after 3 months. Headache and trigeminal neuralgia also disappeared. PMID- 3336839 TI - Aneurysm recurrence associated with induced hypertension and hypervolemia. AB - A case of angiographic recurrence of a previously clipped large distal basilar aneurysm associated with prolonged hypervolemic and hypertensive therapy for vasospasm is reported. Currently, the most effective therapy for reversing neurological deficits secondary to vasospasm and for augmenting cerebral blood flow is induced hypertension and hypervolemia. The complication of aneurysm enlargement with this therapeutic modality has been postulated but not previously demonstrated. PMID- 3336840 TI - Cerebellar hemorrhage: diagnosis and treatment. AB - We have reviewed the records of 22 patients with spontaneous cerebellar hemorrhage. One question that we considered was whether the increased recognition of this disorder, since the introduction of computed tomography (CT) scanning, had brought about a change in the associated signs and symptoms, as compared with previous series. No such change was found. Nine patients died, four after operation (ventricular shunting in one, clot evacuation in one, both procedures in two patients). The five other patients were considered inoperable, because they showed signs of compression of the caudal brainstem. It is improbable that any of these five could have been saved by immediate ventricular drainage, advocated by some as the only treatment. Thirteen patients were treated conservatively and recovered, although four had a hematoma larger than 3 cm. All these patients had a Glasgow coma scale score of 11 points or more. The level of consciousness may be a better guide in management than the size of the clot. PMID- 3336841 TI - Gliosarcoma developing in close relationship to an abscess cavity injected with thorotrast. AB - A case of an unusual tumor developing at the site of an abscess is reported. The tumor presented 21 years after burr hole drainage of the abscess and instillation of the contrast medium thorotrast. The bizarre nature of the tumor and its immediate proximity to the thorotrast lead the authors to believe that the tumor was caused by the contrast medium. PMID- 3336842 TI - Pseudomeningocele of the lumbar spine. AB - A patient with a lumbar pseudomeningocele after intervertebral disc surgery is reported and the findings of computed tomography and magnetic resonance imaging are described. PMID- 3336843 TI - Symptomatic xanthogranuloma of the choroid plexus of the third ventricle. A new case with ultrastructural study. PMID- 3336844 TI - Intracerebral hemorrhage in a primate model: effect on regional cerebral blood flow. AB - The dynamic changes in regional cerebral blood flow (rCBF), induced by a developing intracerebral hematoma, were studied in eight anesthetized monkeys. Hematomas were generated by allowing femoral arterial blood to enter the caudate nucleus via a stereotactically implanted needle. Intracranial pressure peaked at 51 +/- 8 mmHg at 3 minutes after the ictus, and remained high throughout the 3 hour procedure. Cerebral blood flow was significantly reduced in all brain regions for 1 hour after the ictus. The lowest rCBF values were recorded in the immediate clot penumbra and were below threshold levels for ischemic neuronal damage for 90 minutes after the hemorrhage. PMID- 3336845 TI - Postoperative computed tomographic control of 38 patients with craniopharyngioma. AB - Computed tomography scanning was performed on 38 patients 1-12 years after surgery for craniopharyngioma. Recurrence of the tumor had appeared in nine patients. Thirteen patients had a residual tumor, and 16 were tumor-free after primary surgery. In addition, one patient became tumor-free after total removal of the recurrent tumor. After partial removal, the rate of recurrence was high and the quality of life was impaired. PMID- 3336846 TI - Bilateral traumatic third nerve palsy. AB - Bilateral palsy of the third cranial nerve in a head-injured patient is described. Delayed computed tomography scanning demonstrated a midline necrotic lesion within the mesencephalon ventral to the aqueduct. The lesion, possibly the sequela of a focal contusion, involved both third nerve nuclear complexes and caused paralysis of their voluntary as well as autonomic functions. Gaze mechanisms and long tracts appeared to be less heavily damaged. The literature dealing with third nerve palsy, particularly bilateral cases, from traumatic and other origins is briefly reviewed. PMID- 3336847 TI - Surgical treatment of achondroplastic dwarfs with paraplegia. AB - A retrospective study was done to evaluate the results of surgical intervention on the neurological symptoms associated with achondroplastic dwarfs. Between 1971 and 1979, laminectomy was performed on three patients with thoracolumbar spinal canal stenosis associated with achondroplasia. Simultaneous spondylodesis using Harrington instrumentation in conjunction with extensive laminectomy was performed in the most recent case, and excellent results were obtained. We emphasize, therefore, that neurological deficit caused by kyphotic deformity and instability secondary to extensive laminectomy for achondroplasia can be prevented by this procedure, and thus good results can be anticipated. PMID- 3336848 TI - Multiple meningiomas in a child. AB - We report the case of a 4-year, 5-month-old boy, who had unusual multiple meningiomas occurring simultaneously in the intracranial, intraorbital, and spinal spaces. All lesions were surgically excised and histologically proved. This is the youngest patient with multiple meningiomas without history of neurofibromatosis reported in the literature. PMID- 3336849 TI - Spontaneous retraction of cerebellar tonsils after surgery for Arnold-Chiari malformation and posterior fossa cyst. AB - Magnetic resonance images obtained before and 2 months after surgical decompression for Arnold-Chiari type 1 malformation and an arachnoid cyst revealed retraction of the cerebellar tonsils from the spinal canal into the posterior fossa. This was associated with prominent functional recovery of the patient's ataxia and nystagmus. Such an observation may reflect a benign prognosis. Magnetic resonance imaging is the test of choice for the evaluation of this type of lesion. PMID- 3336850 TI - Periosteal chondroma of the cervical spine: one more cause of neural foramen enlargement. AB - A case of cervical periosteal chondroma presenting with an enlarged neural foramen is described. Review of the literature showed that cervical chondromas are rare but that their characteristic clinical and computed tomographic findings aid in their diagnosis. The computed tomographic findings of two previously reported cases of cervical periosteal chondroma resembled those of the present case. On computed tomographic scanning, an iso-or high-density mass containing stippled calcifications and originating in a posterior cervical neural arch was observed in all three cases. Extensive spinal canal and extradural involvement was observed in five of the seven reported cases, including the one reported here. PMID- 3336851 TI - Supracallosal interhemispheric arachnoid cyst: resolution after intracystic hemorrhage and infection. AB - A case of a large, symptomatic, supracallosal interhemispheric arachnoid cyst is presented. Positive contrast-enhanced computed tomographic (CT) cystography after stereotactic puncture and aspiration demonstrated lack of communication between the cyst and the subarachnoid space or ventricular system. A cystoperitoneal shunt was successful in relieving the patient's symptoms for 5 years. A delayed shunt infection after gynecologic surgery necessitated removal of the shunt, and was complicated by asymptomatic intracystic hemorrhage. Thereafter, serial CT and magnetic resonance imaging scans showed eventual disappearance of the cyst. PMID- 3336852 TI - Middle cerebral artery stenosis--a neglected problem? PMID- 3336853 TI - Dural arteriovenous malformations. PMID- 3336854 TI - How to treat glioblastomas. PMID- 3336856 TI - Research and the humane treatment of animals. PMID- 3336855 TI - Neurotrauma: the Australian experience. PMID- 3336857 TI - Preoperative determination of the level of spinal cord lesions from the killed end potential. AB - To determine preoperatively the level of lesions in acute cervical cord injury, the killed end potential of the spinal cord was recorded with a pair of electrodes placed in the spinal epidural space, one initially being placed rostrally to the lesions for obtaining recordings and the other placed caudally to the lesions for stimulation. The level associated with the largest killed end potential was clearly determined without much difficulty, with sequential recordings on stepwise withdrawal of the recording electrode, in four of five cases investigated. In two cases subjected to surgery, the recording electrode left in place at the level associated with the largest killed end potential was found to be located at, or a few millimeters below, the center of the lesions. This demonstrates the preoperative localizing value of the killed end potential for determining the level of lesions responsible for myelopathy. PMID- 3336858 TI - Effects of cyclosporin A and predegeneration on survival and regeneration of peripheral nerve allografts in rabbits. AB - Axonal regeneration across 64 median nerve grafts in 34 rabbits was studied histologically to determine the optimal conditions for nerve allografting. Axonal regeneration across allografts in cyclosporin A-treated animals was satisfactory, but it occurred more slowly and with more inflammation and fibrosis than in autografts. Without immunosuppression, fresh allografts were rejected. However, in immunocompetent hosts, allografts rendered less immunogenic by predegeneration were not rejected, and axonal regeneration occurred. The combination of cyclosporin A and nerve graft predegeneration produced the most substantial axonal regeneration, comparable to autografts. The observations suggest that nerve allograft survival may be optimally effected by cyclosporin A treatment coupled with reduction in the immunogenicity of the grafts, such as by predegeneration. PMID- 3336860 TI - Interruption of the vena cava by means of the Greenfield filter: expanding the indications. AB - Between 1978 and 1985, 88 patients underwent insertion of the Greenfield vena cava filter. In 21 of the 88 patients (23.9%) the filter was inserted prophylactically. Sixteen of the 21 prophylactic insertions were performed before total joint replacement in patients with a history of venous thromboembolism. Operative morbidity (4.6%) was minor and occurred only early in the series. The operative mortality rate was 4.6%. None of the deaths were related to filter insertion or pulmonary embolism. Follow-up in 65 patients (73.9%) ranged from 1 to 60 months (mean, 16.4 months). Leg edema developed in 9.2% (6/65), stasis ulceration in 3.1% (2/65), caval occlusion in 7.5% (3/40), and recurrent nonfatal embolism in 3.1% (2/65) of the patients. In the patients who received prophylactic filters before total joint replacement, there were no filter-related complications or episodes of pulmonary embolism. This series confirms the safety and effectiveness of the Greenfield filter and suggests that the indications for its use might be liberalized to include prophylactic insertion of the device in certain high-risk patients. PMID- 3336859 TI - Cooper's ligament repair: a 25-year experience with a single technique for all groin hernias in adults. AB - In the belief that recurrences will be lower if all defects are repaired at the original operation, I performed a Cooper's ligament repair on all groin hernias in adult patients between 1959 and 1984, regardless of the hernia type. This series includes 1142 repairs in 942 patients. Follow-up has been 97%, with 80% of the patients being personally examined by the author. Excluding late deaths, 906 repairs in 747 patients have been followed up for an average of 9 years. There have been 18 recurrences, for a recurrence rate of 2% of live repairs. This breaks down to 1.9% for 779 primary hernias and 2.4% for 127 recurrent hernias. In primary hernias only the recurrence rates are 3.5% for 289 direct hernias, 1.1% for 459 indirect hernias, and 0% for 31 femoral hernias. Seventeen of the 18 recurrences have been indirect along the cord in a subgroup of 147 repairs done with a subcutaneously transplanted cord and followed for an average of 17.4 years (recurrence rate, 11.6%). This method was discarded in 1972. There has been only one recurrence in 572 repairs with the cord left in the natural position and followed for an average of 7.1 years (recurrence rate, 0.2%). This shows the value of not superimposing the internal and external rings (90% confidence limits that the recurrence rate is less than 0.7%). There has been no recurrence in 154 repairs in female patients or 33 repairs with orchiectomy followed for 8.1 and 8.8 years, respectively. A Cooper's ligament repair gives a strong posterior wall and repairs all the defects that can occur in the groin. It can be done safely on all adult groin hernia patients, with a recurrence rate lower than those reported for selective methods of repair. PMID- 3336861 TI - Skin-flap coverage of polytetrafluoroethylene vascular access graft exposed by previous infection. AB - In selected patients with localized infection of polytetrafluoroethylene graft arteriovenous fistulas, the access route can be preserved by treatment with antibiotics and surgical drainage. However, such treatment may result in exposure of the graft, which in itself is a threat to continued survival of the graft. This article describes a simple method that has been successfully used to achieve skin coverage of such grafts. PMID- 3336862 TI - Lumbar artery aneurysm with acute aortic occlusion resulting from chiropractic manipulation: a case report. AB - A 44-year-old man with an acute aortic occlusion after chiropractic manipulation was found to have a lumbar artery aneurysm. This article presents a previously undescribed entity, a lumbar artery aneurysm, which manifested as a unique cause of distal aortic occlusion in a patient with chronic back pain. PMID- 3336864 TI - Blood glucose and cardiac resuscitation. PMID- 3336863 TI - Bilioportal fistula as a complication of choledochoduodenostomy. AB - A bilioportal fistula is rare. We report the case of a patient who had a bilioportal fistula 6 years after a choledochoduodenostomy. Percutaneous transhepatic opacification showed the bilioportal fistula to be associated with a thrombosed portal vein and a cavernous formation. Treatment consisted of separate percutaneous drainage of the portal and biliary tracts. Closure of the fistula was obtained by progressive proximal intrahepatic portal thrombosis. Our case contrasts with the four other cases of bilioportal fistula published in the literature in that (1) there was an absence of biliary lithiasis and (2) we did not use surgical treatment. The most likely explanation for our case of bilioportal fistula is an infectious complication related to the choledochoduodenostomy. PMID- 3336865 TI - Extraperitoneal aortofemoral bypass. PMID- 3336866 TI - Investigating shunt occlusions. PMID- 3336867 TI - Ineffective intragastric bubbles. PMID- 3336868 TI - Congenital venous valvular aplasia of the lower extremities. AB - A 10-year-old girl had bilateral, symmetrical swelling of the lower extremities, which had been present since the age of 1 year. Noninvasive vascular laboratory measurements of the ambulatory venous pressure, venous recovery time, and maximum venous outflow revealed profound bilateral lower extremity venous valvular incompetence. Duplex imaging of the veins of the lower extremities demonstrated no evidence of thrombosis, and no venous valves could be imaged. On phlebography, the patient was found to have no venous valves in the superficial and deep systems of the leg. We conclude that congenital absence of the venous valves of the lower extremities is almost certainly underdiagnosed and that the vascular laboratory can accurately and easily differentiate between lymphedema and venous valvular imcompetence. Such differentiation may have therapeutic implications. PMID- 3336869 TI - Biofragmentable bowel anastomosis ring: comparative efficacy studies in dogs. AB - Three studies were conducted in a total of 178 dogs to determine the efficacy of a biofragmentable bowel anastomosis ring (BAR) composed of polyglycolic acid and 12.5% barium sulfate. Wound strength and healing of BAR, suture, and staple colonic anastomoses were compared for intervals of up to 1 year. The effect of systemic steroid treatment and BAR size on anastomotic wound strength and healing was also studied. The BARs fragmented at a mean time of 15.06 days postoperatively and were passed in the feces without injury. Wound strength was determined by measurements of the pressure required to burst the anastomosed colonic segment and measurements of the tension required to break 10 mm wide longitudinal strips of the anastomosed segment. The studies demonstrated that wound strength had progressed to a point where continued mechanical support (with sutures or staples) was no longer required by 14 days in both nontreated and steroid-treated dogs. Gross healing evaluations at 21 days and beyond showed no differences due to anastomotic method. Microscopic evaluations suggested that residual granulation tissue was less at the sites of BAR asastomoses than at sites of suture or staple anastomoses at the 1-year interval, suggesting that healing may be better with BAR than with standard methods of colon anastomosis. PMID- 3336870 TI - An automatic autotransfusion system with a centrifugal pump: a hematologic evaluation in dogs. AB - The requirements that have to be met by an on-line autotransfusion system (ATS) in case of massive blood loss are a sufficient capacity for reinfusing the shed blood, an optimal hemocompatibility, ability to prevent reinfusion of aspirated air, and ease of operation. In a previous study we tested a diaphragm pump in our pneumatically driven ATS that met these requirements. In this study a centrifugal pump was used as an outflow pump in otherwise the same system. A centrifugal pump has important advantages: It prevents the occurrence of massive air embolism, accidental obstruction of the outflow line will not cause bursting of the tubing, and there is no spallation. There are also indications that a centrifugal pump causes less stimulation of the coagulation cascade than do other pumps. Because of these advantages, we were interested in the hemocompatibility and pumping characteristics of the centrifugal pump in our ATS. From this study we conclude that the hemocompatibility of the centrifugal pump was not significantly different from that of the previously tested diaphragm pump. Also, the system can easily and safely be operated by non-specialized personnel. Because of the advantages, especially in pumping characteristics, the centrifugal pump is our choice in on-line ATSs. PMID- 3336871 TI - Morphologic and nutritional responses to intestinal patching following intestinal resection. AB - Growth of neomucosa has been investigated as a means to increase intestinal surface area in the short-bowel syndrome. Functional neomucosa grows over patched intestinal defects, but the effect of the patching procedure on absorption is unknown. The purpose of this study was to determine morphologic and nutritional responses to intestinal patching after resection. Fifteen dogs (13 to 19 kg) underwent either 75% resection of the small intestine (control group, n = 5), simultaneous resection and patching of the intestinal remnant with colon serosa (simultaneous group, n = 5), or resection with patching 12 weeks later (delayed group, n = 5). Caloric intake was standard in the three groups. Animals were killed 40 weeks after resection or patching. At that time, defects were 95% covered with neomucosa in both patched groups. Intestinal remnant length increased significantly in controls (139 +/- 20% initial length) compared to the simultaneous group (99 +/- 6%, p less than 0.05) but not to the delayed group (119 +/- 11%). Villous height of intestinal mucosa was greater in the control and delayed groups than in the simultaneous group (714 +/- 36 and 624 +/- 111 versus 535 +/- 54 micron, p less than 0.05). Fasting gastrin levels were significantly greater in patched animals than after resection alone (p less than 0.05). Intestinal transit by barium meal was significantly longer in patched animals (18 +/- 7 minutes versus 11 +/- 6, p less than 0.05). Body weight and serum albumin level were significantly lower in patched animals at death. Fecal weight, moisture, and fat excretion were significantly increased in the simultaneous group. Although intestinal patching results in the growth of neomucosa and prolonged transit time, it has a deleterious effect on absorption and nutritional status. In part, this may be related to inhibition of intestinal adaptation and gastric hypersecretion in patched animals. PMID- 3336872 TI - Pathogenesis of nodular goiter and its implications for surgical management. AB - Despite sufficient iodine supply, goiter continues to be of considerable surgical significance in formerly endemic countries. It now appears that iodine deficiency and increased thyrotropin stimulation are not the only causes of goiter. Xenotransplantation of human thyroid tissue onto nude mice allowed study of the regulation of growth and function in human goiter tissue. Grafts of human thyroid tissue growing in nude mice could be shown to react to endogenous mouse thyrotropic stimulation and suppression. 131I autoradiographs of xenotransplanted goiter tissue showed as marked a heterogeneity as did the original goitrous tissue prior to transplantation. There was no firm correlation between the morphologic appearance of a follicle and its iodine metabolism. Scintigraphically "cold" and "hot" goiter tissue differed from each other quantitatively but not qualitatively; i.e., both "hot" and "cold" tissue were composed of metabolically active and nonactive follicles. Iodine organification was not completely suppressible by thyroxine treatment; this indicates autonomous functional activity. The distribution of proliferating tissue labeled by 3-H-thymidine did not parallel the distribution of functionally active tissue labelled by 131I. Thyroxine treatment did not completely inhibit 3-H-thymidine incorporation, indicating autonomous growth. Thus, our pathogenetic concept of goiter formation is based on three mainstays: (1) goiter heterogeneity, (2) autonomy of growth and function, and (3) dissociation of growth and function in human goiter tissue. Thus, the surgeon dealing with goiter ought to remove all pathologically altered tissue, i.e., nodular tissue, irrespective of its appearance on scintiscans. PMID- 3336873 TI - The energy costs of surgery as measured by the doubly labeled water (2H218O) method. AB - Energy expenditure before and after surgery was determined in seven patients by the doubly labeled water (2H218O) method (DLW). The values were compared with values obtained by respiratory gas exchange by means of a metabolic measuring cart (MMC). Patients were maintained on total parenteral nutrition before and after trauma. The principal finding was an increase in the rate of CO2 production of 11.9 +/- 5.0% after surgery. This corresponds to a 267 +/- increase in energy expenditure (p less than 0.05). No trauma-associated change in energy expenditure was found with the MMC. The correlation of preoperative values from MMC and DLW was not statistically significant (r = 0.25), nor was the correlation of MMC and the Harris-Benedict equation, but the correlation of DLW with Harris-Benedict equation was statistically significant (r = 0.73, p less than 0.05). We suggest that the discrepancy is because the DLW method measures the cumulative energy expenditure over a period, whereas the MMC gives a "spot" measurement. PMID- 3336874 TI - [Wage committee adjustment is out of joint]. PMID- 3336875 TI - [Mental health care--and the unused resources]. PMID- 3336876 TI - [Why the Norwegian Nurses' Association says 'no' to nursing assistants in operating rooms. Interview by Bjorn Arild Ostby]. PMID- 3336877 TI - [Continuing education in operating room nursing]. PMID- 3336878 TI - [Nursing shortage. Ending it before one has started. Interview by Kjell Arne Bakke]. PMID- 3336880 TI - Promoting the nursing profession. PMID- 3336879 TI - [Solid majority in Norwegian Nurses' Association is for membership in AF (Academic Joint Organization)]. PMID- 3336881 TI - In vivo metabolism of nasally instilled benzo[a]pyrene in dogs and monkeys. AB - Metabolism of inhaled materials deposited in the nasal cavity potentially influences their biological fate and toxicity. Metabolic enzymes, including cytochrome P-450-dependent monooxygenases, are not evenly distributed throughout the nasal cavity. The purpose of this study was to determine whether benzo[a]pyrene (BaP) deposited in the nasal cavity could be metabolized and cleared by the nasal tissue in the ethmoid and maxillary turbinate regions of Beagle dogs and cynomolgus monkeys. Nasopharyngeal mucus was collected at frequent intervals during periodic nasal instillations of BaP (and for dogs 24 h after instillation) for analysis of BaP and its metabolites. During and up to 48 h after nasal instillation of [14C]BaP, blood, urine and feces were collected to determine BaP clearance from the nose. High pressure liquid chromatographic analysis of organic phase extracts of nasopharyngeal mucus demonstrated that [14C]BaP instilled in either turbinate region was metabolized to dihydrodiols, quinones, phenols and tetrols in both species. Phenols were the major metabolic product, although all treated animals produced trans-7,8-dihydrobenzo[a]pyrene 7,8-diol. The dog mucus sampled at 24 h had no detectable radioactivity. The excreta from both species contained only small amounts of the instilled radioactivity. There was no distinctive pattern of metabolite production based on instillation site. PMID- 3336882 TI - Examination of minoxidil-induced acute cardiotoxicity in miniature swine. AB - Minoxidil, a vasodilating antihypertensive agent, was given orally in doses of 1, 3 or 10 mg/kg to miniature swine on 2 consecutive days. Mean arterial pressure decreased and heart rate increased most consistently after the 10 mg/kg dose. However, all 3 doses of minoxidil induced myocardial hemorrhages and/or left ventricular papillary muscle necrosis within 24 h after the second dose. Necrosis, characterized by hypercontraction of muscle cells and myofibrillar damage, occurred in 1 of 8 pigs given 1 mg/kg, 3 of 13 given 3 mg/kg and 7 of 14 given 10 mg/kg of minoxidil. The pharmacological effects of minoxidil, hypotension and reflex tachycardia, probably led to ischemia and necrosis in left ventricular papillary muscles. Gross hemorrhages involving the left atrium and to a lesser extent the left ventricle were found in 4 of 8 pigs given 1 mg/kg, 9 of 13 given 3 mg/kg and 11 of 14 given 10 mg/kg of minoxidil. The atrial lesions were manifested grossly by diffuse redness and microscopically by interstitial edema, extravasation of erythrocytes and infiltration of areas around small arteries and arterioles with acute and chronic inflammatory cells. The hemmorhagic areas were concentrated along the epicardial surfaces, and to a lesser extent along the endocardial surfaces. Atrial lesions induced by minoxidil preferentially involve the left atrium in pigs and the right atrium in dogs. These differences may be related to the anatomic patterns of coronary circulation in the 2 species. PMID- 3336883 TI - Effect of long-term feeding of aluminium chloride on hexokinase and glucose-6 phosphate dehydrogenase in the brain. AB - Rats were fed 100 microM AlCl3 for 1 year in their drinking water, then killed and their brains homogenized in 0.1 M Tris (pH 7.4). The 800 g supernatants were assayed for Al3+ and the activities of acetylcholine esterase (ACE), hexokinase and glucose-6-phosphate dehydrogenase (G6PDH). The concentrations of Al in the homogenates, as computed on the original brain for the control and Al fed group were 40 ng and 80 ng/g wet wt, respectively. The activity of ACE was the same in both groups but that of hexokinase and G6PDH in the Al-fed group was about 73% and 80%, respectively, of the control. Dialysis restored the G6PDH but increased the hexokinase of the control group 2-fold and that of Al-fed group 2.7-fold. Thus at this elevated level it was same in both groups. The contribution of Al from the undialysed homogenates during assay was too low to account for the inhibition. It is therefore suggested that a dialyzable inhibitor for hexokinase is normally present in the brain and that Al feeding increases its concentration to further inhibit the utilization of glucose. PMID- 3336884 TI - Effect of butylated hydroxyanisole added in vitro or administered to rats on N,N dibutylnitrosamine and N-butyl-N-(4-hydroxybutyl)nitrosamine metabolism by post mitochondrial supernatant of liver homogenates. AB - The effect of butylated hydroxyanisole (BHA) on P-450-dependent omega hydroxylation of N,N-dibutylnitrosamine (NDBA) to N-butyl-N-(4 hydroxybutyl)nitrosamine (BBN), and the further oxidation of BBN to N-butyl-N-(3 carboxypropyl)nitrosamine (BCPN) by the alcohol/aldehyde dehydrogenase system was investigated using the post-mitochondrial supernatant of liver homogenates (S9) from acutely and chronically BHA pretreated animals or S9 fractions from untreated rats with BHA added. Acute oral BHA (50 and 250 mg.kg-1) did not change NDBA omega-oxidation, which was reduced by 35% only when the compound was administered 0.5% in the diet for 3 weeks. BCPN formation from BBN was unaffected by acute and chronic BHA pretreatment. In order to verify whether BHA or its metabolite(s) had a direct effect on NDBA and BBN oxidation, the compound was added to S9 fractions from untreated rats at various concentrations. Only when BHA concentrations were equimolar or in a 10-fold molar excess to the substrate concentration, we observed 30-50% inhibition of BBN formation and a reduced BCPN formation (60-80% of control values), from BBN. Thus, only at very high BHA concentrations could we confirm the inhibition of P-450-dependent mixed function oxidase and alcohol dehydrogenase activities involved in the metabolism of NDBA and BBN. PMID- 3336885 TI - Acrylonitrile depletes glutathione without changing calcium sequestration in hepatic microsomes and mitochondria. AB - Acrylonitrile administered either in vivo or in vitro reduced the level of non protein thiols, GSH and GSSG in rat liver (in vivo) and liver microsomes (in vitro). It neither influenced protein thiols nor calcium sequestration in the microsomes and mitochondria. The fact that the GSSG level was not increased indicates that a mere unoxidative depletion of GSH does not lead to impaired hepatocyte Ca homeostasis, which has been associated with decreased GSH:GSSG ratio. An opposite effect was caused by CCl4 which did not considerably change the protein and non-protein SH, but strongly decreased microsomal calcium sequestration. PMID- 3336886 TI - Glutathione is involved in the early cadmium cytotoxic response in human lung carcinoma cells. AB - Depletion of cellular glutathione (GSH) has been shown to sensitize A549-T27 human tumor cells to the cytotoxic effects of Cd2+. In this study the temporal and quantitative relationships between reduced cellular GSH levels and cadmium cytotoxic response in these cells were further investigated. Exposure of A549-T27 cells to 10 mM buthionine sulfoximine (BSO) for 8 h decreased their GSH level by 65%. This GSH level remained relatively constant for 8 h in the presence or absence of BSO, but recovered to 83% of the normal cellular level 24 h after removal of BSO. Exposure to 5 microM Cd2+ for 8 h did not significantly change cellular GSH levels. Pretreatment of the A549-T27 cells with 10 mM BSO for 8 h and subsequent exposure of the cells to Cd2+ for 10 days, with or without concurrent treatment of 10 mM BSO during the first 8 h of Cd2+ exposure, resulted in disappearance of the 5 microM Cd2+ threshold for cytotoxic response and reduction of the LC50 from 31 microM Cd2+ to 21 microM. Similar results were obtained when BSO pretreated cells were exposed to Cd2+ for 8 h. The threshold for cytotoxic response of 10 microM Cd2+ disappeared and the LC50 was reduced from 60 microM to 29 microM Cd2+ (with concurrent BSO treatment) and 30 microM (BSO pretreatment only). The results show that GSH plays an important role in early cellular protective responses to Cd2+. PMID- 3336888 TI - Carotid body tumor: unusual cause of transient ischemic attacks. AB - Carotid body tumors are an unusual cause of transient ischemic attacks. The cases reported in the literature have been limited to the postoperative period. We report a patient with bilateral carotid body tumors and transient ischemic attacks as the presenting syndrome. A low-perfusion state could explain his symptomatology. PMID- 3336887 TI - Failure of heparin to prevent progression in progressing ischemic infarction. AB - Anticoagulation with heparin is frequently recommended for patients with progressing ischemic cerebral infarction, yet little data is available detailing the acute results of treatment with this agent. We report the results of continuous intravenous heparin treatment in 36 consecutive patients admitted with progressing ischemic infarction, all of whom had computed tomography scans to exclude the diagnosis of hemorrhage prior to treatment. Overall, 18 of 36 (50%) had continued neurologic worsening despite treatment. The incidence of further worsening was greater in carotid territory infarctions (14 of 19, 74%) than in either vertebrobasilar (2 of 8, 25%) or lacunar (2 of 9, 22%) infarctions (p less than 0.05, Fisher's exact test). These observations suggest that additional controlled studies of the efficacy of heparin in progressing ischemic infarction are warranted. PMID- 3336889 TI - Pure motor hemiplegia secondary to a saccular basilar artery aneurysm. AB - Pure motor hemiplegia is the most commonly encountered lacunar syndrome and is classically associated with small infarctions in the contralateral internal capsule or basis pontis. Pure motor hemiplegia has also been observed secondary to a wide variety of other vascular and nonvascular focal central nervous system processes. We describe a patient with pure motor hemiplegia associated with a saccular basilar artery aneurysm causing a lacunar infarction of the cerebral peduncle. PMID- 3336890 TI - Prognosis of high-risk patients with nonoperated symptomatic extracranial carotid tight stenosis. AB - Forty-five patients with symptomatic (20 with transient ischemic attack, 25 with minor stroke) greater than or equal to 75% stenosis of the cervical internal carotid artery had no endarterectomy and received only medical therapy because the surgical risks (severe cardiac disease, chronic obstructive pulmonary disease, hypertension or diabetes with systemic complications, aortic aneurysm) were believed to be unacceptable. During follow-up (mean 48 months), occlusion of the internal carotid artery developed without symptoms in two patients and with symptoms in three patients. The cumulative stroke and/or death rate was 24% at 2 years and 50% at 6 years. The ipsilateral infarct rate was 10% after the first year, but decreased markedly thereafter (2.4% per year), and one third of these infarcts were probably lacunes due to hypertensive small vessel disease. Overall, stroke related to previously symptomatic internal carotid artery stenosis was not the major problem during follow-up but was largely overcome by other strokes and cardiac death. PMID- 3336891 TI - Local embolism from vertebral artery occlusion. AB - Basilar artery territory stroke may result from embolism arising from the site of vertebral artery occlusion. This stroke mechanism (local embolism) has been well documented in the middle cerebral artery territory from extracranial internal carotid artery disease but not fully appreciated in the vertebral basilar circulation. We report two patients whose clinical presentation indicated major basilar artery territory infarction documented by angiography to be the result of vertebral artery occlusion and artery-to-artery embolism. Vertebral artery occlusion has often been associated with a benign course, but under certain circumstances embolism to the basilar artery may complicate the outcome. PMID- 3336892 TI - Ataxic hemiparesis--ventrolateral nucleus of the thalamus: yet another site of lesion. PMID- 3336893 TI - Leukocyte rheology in recent stroke. PMID- 3336894 TI - Analysis of regional blood flow data. PMID- 3336895 TI - Recurrent cerebral infarction and antibodies to cardiolipin: a case report. PMID- 3336896 TI - Post-stroke depression and lesion location. PMID- 3336897 TI - A suitable method to select gerbils with incomplete circle of Willis. PMID- 3336898 TI - Stroke in thyrotoxicosis with atrial fibrillation. AB - Chronic atrial fibrillation is associated with an increased risk of stroke. In elderly patients with thyrotoxicosis, atrial fibrillation is frequently encountered, and the true risk of cerebrovascular events in these patients is controversial. We retrospectively studied 610 patients with initially untreated thyrotoxicosis, 91 (14.9%) of whom had atrial fibrillation, with the highest frequency in the elderly patients. The risk of cerebrovascular events, with special attention to the first year after the diagnosis of thyrotoxicosis, was calculated using logistic regression methods with age, sex, and atrial fibrillation as independent variables. Only age was an important risk factor (p less than 0.005), whereas sex and atrial fibrillation were not significant (p = 0.09 and p = 0.17, respectively) as independent risk factors. This is contrary to other studies of patients with thyrotoxic atrial fibrillation, and the need for further clarification of this issue is clear. From our study the indication for prophylactic treatment with anticoagulants for prevention of stroke in thyrotoxic atrial fibrillation seems doubtful, especially as no controlled studies of such treatment in patients with atrial fibrillation are currently available. PMID- 3336899 TI - Evolving focal cerebral ischemia in cats: spatial correlation of nuclear magnetic resonance imaging, cerebral blood flow, tetrazolium staining, and histopathology. AB - The spatial correlation of nuclear magnetic resonance imaging (NMRI) and cerebral blood flow (CBF) may improve our ability to identify ischemic brain lesions and may provide further insight into the pathophysiology of early cerebral ischemia. Eleven pentobarbital-anesthetized adult cats underwent exposure of the common carotid arteries bilaterally and the right middle cerebral artery through a transorbital approach. Baseline NMRI images were obtained with a single spin echo, multislice technique using a 0.6-T field, 0.4-cm slice thickness, and a surface coil. Focal ischemia was produced with right middle cerebral artery occlusion and potentiated with bilateral common carotid artery ligation. Sequential NMRI studies were then performed at 1, 2, 4, 6, and 12 hours or until CBF was determined in the same cats using [14C]iodoantipyrine at either 2 (n = 2), 4 (n = 2), 6 (n = 2), or 12 (n = 1) hours after the time of occlusion. This protocol allowed temporal and spatial correlation of NMRI and CBF. Alternate 5-mm brain slices were incubated with 1% 2,3,5-triphenyltetrazolium chloride (TTC) for 45 minutes at 37-41 degrees C and frozen in liquid Freon for later autoradiographic CBF determination. Four cats were studied only with NMRI and TTC (not CBF). The correlation between areas of increased NMRI signal intensity observed in T2-weighted images (repetition time 2,000 msec, echo time 120 msec), vital staining with TTC, low CBF, and routine histology was evaluated. During the early phase (less than 6 hours), T2-weighted NMRI changes were localized to the central ischemic gray matter areas, as defined in the later CBF images, with no involvement of the white matter. By the twelfth hour the NMRI changes involved the entire ischemic area including gray and white matter. The initial visible changes seen on T2-weighted NMRI are suggestive of cellular edema, and the later changes are characteristic of vasogenic edema. The spread of NMRI changes compared with the ischemic area determined from autoradiographic CBF is consistent with the previously described biphasic evolution of ischemic injury. These data suggest that T2-weighted NMRI could be used clinically to delineate areas of acute ischemic stroke. PMID- 3336900 TI - Stroke rehabilitation outcome: impact of coronary artery disease. AB - The frequency of clinically significant coronary artery disease (CAD) among stroke patients and the impact of CAD on stroke rehabilitation were studied in 132 patients with first thrombotic or embolic stroke who participated in comprehensive rehabilitation. Sixty-one patients (46%) had a history of CAD, and 16 of the 61 also had congestive heart failure (CAD-CHF). Patients with CAD, and especially those with CAD-CHF, had significantly longer intervals from stroke onset to rehabilitation admission (p less than 0.001), and once in rehabilitation they experienced three times as many cardiac complications (p less than 0.001). While all patient groups improved function during rehabilitation, those with CAD and CAD-CHF improved significantly less than did those without CAD (p less than 0.01). Patients with CAD did least well with rolling, moving in bed, transferring from a wheelchair to bed, and walking. CHF not only adversely influenced overall function and mobility task performance but also affected the potential for achieving functional gains. These data suggest that specific measures of function and rehabilitation are affected by CAD and that the levels of achievement for patients with CAD-CHF are limited. PMID- 3336901 TI - Intracerebral hemorrhage in a Japanese community, Hisayama: incidence, changing pattern during long-term follow-up, and related factors. AB - The incidence of intracerebral hemorrhage over 13 years is compared between two Hisayama cohorts. Among men aged 40 years or older, the annual incidence declined significantly from 3.1/1,000 in the early cohort (1961-1970) to 1.2/1,000 in the recent cohort (1974-1983). Massive ganglionic hemorrhage decreased, while small or medium-sized intracerebral hemorrhage increased in the recent cohort on pathologic or computed tomographic examination. These trends could be due to the reduced prevalence of hypertension in the Hisayama population. The association of serum total cholesterol with intracerebral hemorrhage is discussed based on the results during a 22-year follow-up period. PMID- 3336902 TI - Moyamoya disease in Taiwan. AB - Moyamoya disease occurring in Chinese has been inadequately described. Here we report 13 cases of this disease identified by review of 3,200 cerebral angiograms performed between August 1979 and March 1986. Nine were males and four were females; there were 12 adults (aged 34-51 years) and one child (aged 11 years). All had hemorrhagic strokes with one exception, a patient with an occipital infarction. Intraventricular hemorrhage was noted by computed tomography in 10; five of these emanated from the caudate nucleus. A localized hematoma without intraventricular hemorrhage was found in two. All 13 angiograms had smokelike basal anastomoses with various degrees of stenosis or occlusion of the anterior portion of the circle of Willis; the involvement was bilateral in 12 and unilateral in one. Aneurysms were found in two patients, one in the anterior communicating artery and the other in the left anterior choroidal artery. Eleven patients recovered from the initial stroke, but two died with recurrent hemorrhage. This series differs from the series reported in Japan by the predominance of adult males. The high incidence of intraventricular hemorrhage and intracerebral hematoma is not in keeping with the previous Chinese series, in which subarachnoid hemorrhage was suspected to be the major clinical manifestation. PMID- 3336903 TI - Prevalence of stroke in the Parsi community of Bombay. AB - A door-to-door survey of 14,010 Parsis living in colonies in Bombay, India, screened people for possible neurologic diseases. High school graduates, social workers, and a medical student administered a questionnaire that had been shown in a pilot study to have a sensitivity of 100% for identifying persons with stroke. Neurologists used defined diagnostic criteria to evaluate those who were positive on the screening survey. One hundred eighteen persons (57 men, 61 women) suffered from stroke (842.3 cases/100,000 population). The age-specific prevalence ratios increased with age for both sexes and for each age group. Age adjusted prevalence ratios were slightly higher for men than for women. The most common type of stroke was ischemic (114 cases). PMID- 3336904 TI - Combination of aminocaproic acid and nicardipine in treatment of aneurysmal subarachnoid hemorrhage. AB - Antifibrinolytic drugs reduce the risk of rebleeding during the first 2 weeks after aneurysmal subarachnoid hemorrhage. However, they do not lower overall mortality, largely because of an increased incidence of cerebral ischemia. The usefulness of antifibrinolytic drugs might be increased if a method to prevent or control vasospasm in patients were to be developed. We recently completed late Phase I and Phase II studies of the calcium ion blocking drug nicardipine in 67 patients treated within 1 week of subarachnoid hemorrhage. Of these 67 patients, 42 had delayed operations and were treated concomitantly with the antifibrinolytic drug aminocaproic acid (1.5 g/hr) for an average of 6 days before surgery. The outcome of these 42 patients is the subject of this report. Fifteen of 42 patients were treated with the lower dosage levels of nicardipine (0.4-4.5 mg/m2/hr), and 27 patients were treated at the highest dosage level (6.0 mg/m2/hr). Using the World Federation of Neurological Surgeons scale for subarachnoid hemorrhage, at admission 18 patients were Grade I, 15 were Grade II, 6 were Grade III, and 3 were Grade IV. Five patients (12%) developed clinical signs of deterioration suggestive of cerebral ischemia with concomitant evidence of vasospasm on arteriography. These patients were all treated with hypervolemic hypertensive therapy. Only one patient (2%) developed an infarction from vasospasm. Two patients developed symptomatic hydrocephalus requiring ventriculoperitoneal shunting, and a third patient required a temporary ventriculostomy. The 3-month postoperative outcomes were excellent. Three patients (7%) rebled. Three patients died, two from rebleeding of the aneurysm and one who never regained consciousness from the initial hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336905 TI - Erythrocytes are essential for development of cerebral vasculopathy resulting from subarachnoid hemorrhage in cats. AB - In an effort to determine which blood elements play a critical role in the development of cerebral vasospasm, adult cats were subjected to prepontine injection of either autogenous whole blood or erythrocyte-free blood containing latex beads as a substitute morphologic marker. Seven or 10 days later the cats were anesthetized and perfused with fixative, and the basilar arteries were prepared for light and electron microscopy. Successful clot deposition was confirmed by the presence of numerous erythrocytes or latex beads within the adventitia of vessels. In agreement with previous studies, instillation of whole blood produced luminal narrowing associated with profound ultrastructural changes in all layers of the vascular wall. No significant alterations, however, occurred in arteries bathed in erythrocyte-free blood. These findings suggest first, that erythrocytes are essential for the development of the vasculopathy associated with chronic cerebral vasospasm, and second, that the role, if any, of other blood elements is not autonomous. PMID- 3336906 TI - Occurrence of stroke in a nonhuman primate model of cerebrovascular disease. AB - A relation between hypertension, atherosclerosis, and stroke is well documented in humans. We report a similar relation in two hypertensive cynomolgus monkeys with severe cerebral atherosclerosis. In our primate model hypertension is induced by surgical coarctation of the aorta. These monkeys, when fed an atherogenic diet, develop severe cerebrovascular atherosclerosis. In this setting two monkeys developed spontaneous cerebral hemispheric strokes that occurred during treatment of hypertension. Since the strokes were topographically related to severe atherosclerotic narrowing of cerebral arteries and occurred without evidence of either thrombosis or embolization, they are presumed to be related to disturbances of blood flow. In both humans and animals cerebral perfusion is autoregulated to a constant flow over a wide range of mean arterial blood pressures. In hypertension both the upper and lower limits of autoregulation are increased. With treatment of hypertension readaptation to more normal levels is reported to be inconsistent and slow to develop. It is therefore postulated that the strokes in these two monkeys were due to hypoperfusion as a result of the combination of pharmacologic reduction in blood pressure and severe occlusive atherosclerosis. PMID- 3336907 TI - Biomechanics of brain edema in acute cerebral ischemia in cats. AB - We studied whether the biomechanical properties of brain play an important role in the development of early ischemic brain edema in cats with middle cerebral artery occlusion. Brain tissue pressure, tissue compliance, and tissue resistance were measured from the gray matter in the core and the periphery of the middle cerebral artery territory for 6 hours after occlusion. Regional cerebral blood flow and water content were also measured from the same areas. Ventricular fluid pressure was recorded. Tissue pressure rose gradually in the core, where flow was 6 ml/100 g/min, over 4 hours and then stabilized. The pressure gradient measured between edematous tissue and ventricular fluid was 5.3 mm Hg. Tissue resistance increased 1 hour after occlusion when water content increased to 10 mg/g. Later, when water content increased by 40 mg/g, tissue resistance decreased and tissue compliance increased significantly. In the periphery, where flow was 17.6 ml/100 g/min, tissue pressure rose slightly while tissue compliance and tissue resistance did not change within 6 hours. Our data indicate that as ischemic injury progresses, edema fluid accumulates in highly compliant brain parenchyma, then migrates through highly conductive tissue into the cerebrospinal fluid spaces, driven by the hydrostatic pressure gradient between the edematous tissue and the cerebrospinal fluid. PMID- 3336909 TI - Humor--no nurse manager should be without it! PMID- 3336908 TI - Transient amnesia resulting from vertebral artery dissection. AB - Acute transient amnesia has not been previously associated with vertebral artery dissection. We describe two men with acute onset of dense anterograde amnesia and partial retrograde amnesia resulting from spontaneous vertebral artery dissection. Both amnesic syndromes completely resolved with conservative management. PMID- 3336910 TI - Computers and nursing: learning the language. PMID- 3336911 TI - Orientation's key to future success. PMID- 3336912 TI - CNS skills (clinical nurse specialist): refining nursing diagnosis. PMID- 3336913 TI - A practical approach to managing incontinence. PMID- 3336914 TI - Prediction of donor-specific transfusion sensitization. I. A linear logistic model. AB - Using linear logistic regression, six factors were identified as important predictors of risk of DST sensitization in a group of 195 patients. Factors increasing the risk were: percent panel reactive antibody (PRA), previous transplants, and pregnancy; those decreasing the risk were HLA antigens matched, third-party blood transfusions, and Imuran administration. From this analysis, the magnitude of the effect of each factor on the risk of sensitization was obtained. An equation was then obtained that can be used to compute an estimated probability of sensitization (PS) for each patient. As a test of predictive ability of the model, the PS was calculated for 66 patients in an independent patient group. These observations were arranged according to the estimated probability and then divided into intervals of risk. Overall, for each interval, a very high level of agreement was found between the predicted and actual number of sensitized patients. A total of 16.13 patients were predicted to become sensitized and 17 actually did. PMID- 3336915 TI - Nephrotoxicity of cyclosporine A and cyclosporine G in a rat model. AB - Cyclosporine G (CsG) like cyclosporine A (CsA) is a cyclic endecapeptide where the alpha-amino butyric acid residue in position 2 is replaced by norvaline. We studied the effects of both drugs on renal function in a nontransplant rat model to avoid the additional variable of rejection. Age- and weight-matched pairs of male Sprague-Dawley rats were treated subcutaneously for 21 days with a daily dose of 25 mg/kg bw of either powdered CsA or CsG dissolved in 1 ml of olive oil. A control group (C) received olive oil only. Blood pressure (BP) and creatinine (Cr) were measured on days 0, 7, 14, and 21. On day 22, animals were weighed, anesthetized, and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured using c14 inulin and 3H paraAminohippuric acid, respectively. Renal plasma flow and glomerular filtration rate were unaltered in CsG-treated animals compared to controls but significantly reduced in CsA-treated animals. Histologically, vacuolization and microcalcification were seen in significantly greater frequency among the CsA-treated animals. CsG with lesser nephrotoxic potential may prove to be of use in maintenance of therapy of transplants as well as selected autoimmune disorders. PMID- 3336916 TI - Factors affecting the acceptance of deoxyguanosine-treated thymus allografts. AB - dGuo-treated mouse embryo thymus lobes depleted of lymphoid and dendritic cells are not rejected by normal allogeneic mice despite expression of class I and class II major histocompatibility (MHC) antigens on thymic epithelial cells. Our results suggest that host mice are not tolerant to donor antigens, but treated lobes survive because thymic epithelial cells are not immunogenic. Multiple grafts of dGuo-treated lobes are rejected perhaps because numbers of residual dendritic cells reach a threshold necessary for priming. Mice previously primed by injection of spleen cells reject dGuo-treated thymus lobes, and crossreactions between major and minor histocompatibility antigens can be demonstrated. The acceptance of dGuo-treated thymus allografts by normal mice provides a system for investigating the requirements for priming. PMID- 3336918 TI - Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy. AB - Brain-dead organ donors are depleted of circulating triiodothyronine (T3) and show features suggestive generally of anaerobic metabolism at the tissue level, accompanied by deteriorating hemodynamic function. The principle of single-bolus kinetics with labeled carbon compounds (14C-R), with subsequent measurement of both plasma activity and of exhaled 14C O2 has therefore been used to study glucose, pyruvate, and palmitate utilization under conditions of (1) sedation, (2) brain death, and (3) brain death with T3 therapy in the baboon. Serum lactate and plasma-free fatty acid concentrations were also measured. There was a major change in metabolic oxidative processes following brain death. The rate of glucose, pyruvate, and palmitate utilization was markedly reduced, and there was an accumulation of lactate and free fatty acids in the plasma, indicating a general change from aerobic to anaerobic metabolism. The administration of T3 to the brain-dead baboon resulted in a dramatic increase in the rate of metabolite utilization, and a reduction in the plasma concentrations of plasma lactate and free fatty acids, indicating an apparent reversal from tissue anaerobic to aerobic metabolism. We suggest that T3 should be administered to all brain-dead potential organ donors to correct and maintain a more physiologic metabolic status and thus to improve organ function. PMID- 3336917 TI - Control of pH during hypothermic liver storage. Role of the storage solution. PMID- 3336919 TI - Evaluation of antibody synthesis in broadly sensitized patients. AB - This study was conducted to evaluate the rate of lymphocyte antibody synthesis in broadly sensitized patients. Antibody synthesis was estimated utilizing two approaches. In one, the time required by the antibodies to reach half their original values was determined by quantitating their levels by flow cytometry over periods of several months. In the other approach we measured the rate at which antibodies rose after inducing an artificial reduction by means of plasma exchanges. Patients not previously transplanted and not transfused during the study period showed low antibody synthesis and decreasing panel reactivity. In most previously transplanted patients panel reactivity did not change during the observation period. However, some patients displayed low antibody synthesis activity whereas others produced antibodies at a high rate. Extensive studies in one patient demonstrated active antibody synthesis even though he had not been transfused for more than two years. The results suggest that while frequent plasma exchanges can reduce antibody concentrations, concomitant use of immunosuppression may be needed only in patients shown to be actively producing antibodies. PMID- 3336920 TI - Experimental estimation of the viscous component of ultrasound attenuation in suspensions of bovine skeletal muscle myofibrils. AB - It has been suggested that viscous losses, caused by the motion of myofibrils relative to their environmental fluid, could be the major cause of ultrasound attenuation in muscle. This Paper presents theoretical and experimental estimates of the viscous component of attenuation in suspensions of myofibrils. Experimental estimates were made by monitoring the effects of varying the viscosity and density of the suspending fluid and ranged from 0.55 to 0.72 cm2 g 1 protein at 7 MHz, when expressed as mass attenuation coefficients. This represented 16-22% of the total attenuation measured in suspensions. Corresponding theoretical calculations were lower: 0.44 and 0.21 cm2 g-1 protein, respectively, for suspensions with the myofibrils aligned along and across the direction of sound propagation. It was concluded that most of the attenuation was caused by other absorption processes. PMID- 3336921 TI - Bladder reconstruction after cystectomy: use of ileocecal segment and three-loop ileal reservoir. AB - We report on 11 patients who in 1980-1982 had bladder reconstruction, after cystectomy for bladder cancer, utilizing the ileocecal valve as an antireflux mechanism and a direct urethrocecal anastomosis. They received preoperative irradiation (2,000 rad) and had some early complications such as pelvic abscesses and temporary urinary fistulas. We have since omitted preoperative radiation on cases performed in 1984-1987 and they did not have these complications. PMID- 3336923 TI - Kaposi sarcoma of penis and genitalia: a disease of our times. AB - Penile and/or genital involvement may be an early manifestation of AIDS-related Kaposi sarcoma. Diagnosis may be suggested by history, and epidemiologic and sociologic data. Precise diagnosis can be documented by the urologist by early recognition and biopsy of genital lesions. Early awareness and treatment may control this potentially virulent disease. PMID- 3336922 TI - Primary amyloidosis of lower urinary tract. AB - Primary amyloidosis of the lower urinary tract is a rare condition with an excellent prognosis in most cases. Three patients with this condition are described. In the cases of localized amyloidosis of the urethra and urinary bladder, the clinical presentation mimicked cancer of the respective sites. This was also true in the case of primary systemic amyloidosis involving the bladder. If significant associated systemic or local disease can be excluded, management is symptomatic and expectant. PMID- 3336924 TI - Carcinoma of penis treated with neodymium YAG laser. AB - Sixteen men with squamous cell carcinoma of the penis were treated primarily with the Neodymium Yttrium Aluminum Garnet (Nd:YAG) laser. Five patients had TIS, 9 had T1 tumors, and 2 had T2 carcinoma. All patients had refused traditional therapy of partial penectomy and gave informed consent as to the investigational nature of the Nd:YAG laser photoradiation therapy. Circumcisions and deep tissue biopsies were performed on all patients prior to tumoricidal neodymium photoradiation treatment. The patients were followed from twelve to thirty-six months. At follow-up, 5 patients with TIS had no evidence of recurrent cancer. Of the 9 patients with T1 squamous cell carcinoma of the penis, 6 (67%) were tumor free at a mean follow-up of twenty-six months. The 2 men with T2 carcinoma of the penis had reduction of the tumor mass but were not cured. The obvious advantage of the Nd:YAG laser in treating carcinoma of the penis is preservation of the penis eliminating disfiguring amputation. PMID- 3336925 TI - Endourologic management of upper and mid ureteral calculi: percutaneous antegrade extraction vs transurethral ureteroscopy. AB - Fifty patients requiring intervention for upper or mid ureteral calculi were managed initially with a percutaneous antegrade approach (25 patients) or a transurethral ureteroscopic approach (25 patients). In both groups, a crossover to the other modality was at times utilized to accomplish stone removal. Success for either group was defined as complete stone removal without the need for open intervention. PMID- 3336926 TI - Ureteropelvic junction obstruction during the first year of life. AB - Over the past three years, 28 children less than one year of age, were operated on for ureteropelvic junction obstruction. Our results demonstrate that congenital hydronephrosis most commonly presents antenatally, and that early postnatal correction can be performed safely. The high surgical success rate, with a relatively short hospital stay (3-4 days), is attributed to early diagnosis, when the pelviureteral tissues are relatively healthy and nephron maturation is at maximum. The practice of delaying surgical correction of an obstructed hydronephrotic kidney on the basis of "stable" renal function is unwarranted, since it denies such kidneys their full potential for recoverability. PMID- 3336927 TI - Infertility, chemical exposure, and farming in Iowa: absence of an association. AB - An increased incidence of infertility and abnormal semen analysis has been described in men and experimental animals exposed to agricultural chemicals. These reports led us to review the records of 382 consecutive new male patients who had semen analyses performed at the University of Iowa Hospitals and Clinics. No significant differences in the incidence of abnormalities in either the physical examination or the semen analysis were discovered with respect to occupation or possible exposure to chemical agents. PMID- 3336928 TI - Computed tomographic diagnosis of ectopic ureter with seminal vesicle cyst. AB - A rare case of dysplastic kidney with ectopic ureter entering a cystic seminal vesical is reported. This demonstrates the usefulness of computerized tomography in noninvasively delineating such anomalies. Thus accurate preoperative diagnosis can be done, aiding in surgical planning. PMID- 3336929 TI - Renal adenocarcinoma in benign hyperdense mass. AB - We report a case of a renal adenocarcinoma presenting as a benign hyperdense mass. The etiology and radiologic diagnosis of hyperdense renal masses are presented. PMID- 3336930 TI - Simultaneous aortic and renal artery reconstruction for acute arterial occlusion in solitary kidney. AB - A case is described of the onset of acute renal failure due to renal artery occlusion in a solitary kidney of a sixty-six-year-old woman. She had been treated for severe hypertension due to renal artery stenosis. An aortorenal bypass to revascularized the kidney was combined with repair of an abdominal aortic aneurysm. There was early and full recovery of renal function in the single kidney, and the patient was completely rehabilitated. Review of the literature shows that an aggressive surgical approach to the management of renal artery occlusion is usually followed by excellent results. The pre-existence of renal artery stenosis encourages the formation of a collateral arterial supply which maintains the nutrition of the kidney almost indefinitely, after renal artery occlusion. Revascularization will result in prompt recovery of renal function. PMID- 3336931 TI - Effective outpatient use of polyethylene glycol-electrolyte bowel preparation for radical cystectomy and ileal conduit urinary diversion. AB - In this prospective study we examined the oral electrolyte-overload method of bowel preparation for patients who were to undergo radical cystectomy and ileal conduit urinary diversion. We found it to be a safe and effective mechanical bowel preparation that can be used by outpatients. It was well tolerated and resulted in adequate bowel cleansing and a low incidence of postoperative wound infections and pyelonephritis. A major advantage of this method is that it reduced the period of preoperative hospitalization. PMID- 3336933 TI - Testicular germ cell tumor in patient with Klinefelter syndrome. AB - Although mediastinal germ cell tumors are known to occur with a greater frequency in patients with Klinefelter syndrome, reports of testicular germ cell tumors occurring in such patients are rare. We report a case of a nonseminomatous germ cell tumor in a patient with Klinefelter syndrome and suggest that such an association may occur more frequently than has been reported previously. PMID- 3336932 TI - Synchronous bilateral primary germ cell tumors in patient receiving estrogen therapy. AB - The present report concerns the occurrence of bilateral synchronous germ cell tumors in a sixty-eight-year-old man who received estrogen therapy for eleven months. Although there are previous reports on Leydig cell tumors developing in mice and man receiving estrogens, we have not found any connection between germ cell tumors and estrogen medication reported in the literature. PMID- 3336934 TI - Primary lipogranuloma of male genitalia. AB - Lipogranulomas developing secondarily in the genitourinary system have been reported rather frequently, but primary lipogranulomas without any past history of etiologically related conditions are rare. We report on 2 cases recently encountered in which tumors were diagnosed as sclerosing lipogranuloma on histopathologic examination. PMID- 3336935 TI - Use of ureteroscope to avoid distal ureteral false passages. PMID- 3336936 TI - Urethral pressure profilometry in Scott artificial urinary sphincter. AB - The Scott sphincter models AS 791 and AS 800 were implanted in 22 men with urinary incontinence. Urethral pressure profilometry was used intraoperatively and postoperatively to measure the urethral closure pressure (UCP) and to improve the rate of continence and reduce the risk of erosion. Success was achieved in 20 of 24 patients. The utility of urethral profilometry in these cases is described. PMID- 3336937 TI - Sexual science--bridging the disciplines. PMID- 3336938 TI - Sequence comparison of woodchuck hepatitis virus replicative forms shows conservation of the genome. AB - The complete nucleotide sequence of virion DNA from two isolates of woodchuck hepatitis virus (WHV 7 and WHV 59) was determined along with the sequence of supercoiled DNA from one of those isolates (WHV 7). The sequences of the two WHV isolates were compared with the previously published sequences of two other isolates (WHV 1 and WHV 8). The range of nucleotide sequence variation of the four isolates (1 to 3.5%) was similar to those of HBVs of the same subtype (1.5 to 2%), but less than those of HBVs of different subtypes (8 to 10%). When amino acid sequences from the four WHV isolates were aligned, a consensus sequence could not be obtained at 13 sites. At 11 of 13 sites (7 in polymerase, 2 in presurface, 1 in surface, and 1 in the X region) the viruses could be grouped into pairs, so that WHV 1 and WHV 59 shared one amino acid and/or WHV 7 and WHV 8 shared a different amino acid. WHV 7 was passaged twice in woodchucks and supercoiled DNA was isolated. The nucleotide sequence of WHV 7 supercoiled DNA (derived from liver) was compared to that of WHV 7 virion DNA (derived from serum). Sequence comparison of virion and free supercoiled DNA from WHV 7 showed no nucleotide changes, except for a single nucleotide deletion thought to represent an error during molecular cloning or a defective viral genome. Thus, the nucleotide sequence of two different replicative forms of WHV DNA, separated by two in vivo passages, were virtually identical. PMID- 3336939 TI - Establishment of human glial cell lines chronically infected with the human immunodeficiency virus. AB - Human malignant glioma cells were cotransfected with an infectious molecular clone of the human immunodeficiency virus (HIV) and a selectable drug resistance gene (neo). HIV/neo-positive cell clones were maintained in continuous culture for over 5 months and showed the following characteristics: (i) expression of HIV antigens as detected by indirect immunofluorescence staining in 80-90% of cells; (ii) efficient production of HIV RNA and infectious progeny virus; (iii) minimal cytopathic effects (notably in cell morphology), in contrast to HIV-infected T lymphocytes. These results demonstrate that certain glial cells originating from human brain can support a chronic infection with HIV comparable to that observed in T lymphoid cell lines. The cell lines provide an in vitro model system for studies on the mechanism and biological effects of HIV infection in glial cells, and offer an alternative source of the virus that has not been Adapted to lymphocytes or macrophages. PMID- 3336940 TI - Origin of the hemagglutinin gene of H3N2 influenza viruses from pigs in China. AB - Influenza viruses of the H3N2 subtype similar to Aichi/2/68 and Victoria/3/75 persist in pigs many years after their antigenic counterparts have disappeared from humans (Shortridge et al. (1977). Science 19, 1454-1455). To provide information on the mechanism of conservation of these influenza viruses in pigs, the hemagglutinin (HA) of four isolates from swine derived from Taiwan and Southern China were analyzed antigenically and genetically. The reactivity pattern of these viruses with a panel of monoclonal antibodies indicates that the HAs of these swine viruses were antigenically closely related to duck H3 and early human H3 viruses. Sequence analysis of the H3 genes from three swine viruses revealed that the swine H3 genes are more closely related to the duck genes than to early human H3 virus (A/Aichi/2/68). The degree of sequence homology of these genes is extremely high (more than 96.5%). Furthermore, the deduced amino acid sequence of the three swine HAs at residues 226 to 228 in the proposed receptor-binding site is Gln-Ser-Gly and is common with the majority of avian influenza viruses. These findings indicate that these H3 viruses may have been introduced into pigs from ducks. The HA gene of the fourth swine influenza virus from Southern China was genetically equally related to avian and early human H3 strains although the sequence through the receptor-binding pocket (226 228) was typical of a human H3 virus, suggesting that either this swine HA gene was derived from ducks or an early human H3 virus was introduced into the pig population where the virus accumulated substantial mutations. The present strains revealed genetic heterogeneity of swine H3 influenza viruses in nature. PMID- 3336941 TI - Effect of beet necrotic yellow vein virus RNA composition on transmission by Polymyxa betae. AB - Beet necrotic yellow vein virus (BNYVV) is naturally transmitted by the soil borne fungus Polymyxa betae and usually remains confined to the roots of infected sugarbeets. In naturally infected sugarbeets the virion RNA always consists of four components which are uniform in size in different isolates but when BNYVV is propagated by mechanical inoculation to leaves of Chenopodium quinoa the two smallest RNA components, RNA-3 and -4, may undergo deletion or disappear from the isolate, suggesting that they are only essential for the natural mode of infection. To test this hypothesis, several C. quinoa isolates of BNYVV with different RNA-3 and -4 contents have been retransmitted to sugarbeet root via P. betae. The results show that the two isolates containing no detectable full length RNA-3 and -4 are poorly transmitted and that cases of successful infection are associated with the reappearance of full-length RNA-3 and -4. PMID- 3336942 TI - Temporal analysis of transcription and replication during acute infection with lymphocytic choriomeningitis virus. AB - We have analyzed the accumulation of viral genomic and messenger RNAs in tissue culture cells during the first 24 hr of acute infection with lymphocytic choriomeningitis virus (LCMV). This has allowed comparison of the relative amounts of the genomic L and S RNAs (both genomic sense and genomic complementary sense) and of nucleoprotein (NP) and glycoprotein precursor (GP-C) mRNAs. Using these techniques NP mRNA was detected simultaneously with genomic S RNA, but the amount of NP mRNA accumulating during this period of infection was higher than that of GP-C mRNA. This is consistent with a model for ambisense RNA transcription and replication proposed by D.D. Auperin, V. Romanowski, M. Galinski and D. H. L. Bishop (J. Virol. 52: 897-904, 1984). The accumulation of S RNA exceeded that of L RNA and, for both L and S RNAs, the amount of genomic sense RNA was higher than that of genomic complementary RNA. PMID- 3336943 TI - Concatemerization and packaging of bacteriophage T7 DNA in vitro: determination of the concatemers' length and appearance kinetics by use of rotating gel electrophoresis. AB - During its morphogenesis both in intact infected cells (in vivo) and in lysates of infected cells (in vitro), bacteriophage T7 forms end-to-end concatemers of its mature DNA, a linear, nonpermuted, terminally repetitious DNA. During morphogenesis, in vivo T7 concatemers are packaged in preformed capsids and cut to mature size. In the present study the lengths and appearance kinetics of concatemers formed in vitro from mature T7 DNA have been determined. The following procedures are used here for the first time: (a) 20-35% efficient in vitro concatemerization and packaging of T7 DNA; the mixture used for packaging contained two lysates that together had all T7 gene products, and (b) fractionation of concatemers by rotating gel electrophorsis (RGE), which improves the resolution by length of concatemer-length DNA. Concatemerization at 30 degrees was so fast that some other process must be rate limiting for packaging. The concatemers formed were linear and joined left-end to right-end by complementary base pairing, not by blunt-end ligation. Concatemers formed at 30 degrees were reconverted to mature DNA by packaging in vitro. Reducing the temperature to 0 degrees both slowed concatemerization to the time scale (minutes) needed for control of the extent of concatemerization and reduced packaging to insignificant levels, thereby also uncoupling packaging from concatemerization. At both 30 degrees and 0 degrees bands of discrete-length concatemers were observed by RGE. The lengths were n times the length of mature T7 DNA; n was found to be any integer from 2 to 15. The bands were stronger at 0 degrees than they were at 30 degrees in comparison to a background of heterogeneous DNA. No evidence for the favoring of any value of n was found. In addition, it was found by two-dimensional agarose gel electrophoresis that a comparatively small amount of circular DNA was produced in vitro. PMID- 3336944 TI - Time course of virus-specific macromolecular synthesis during rubella virus infection in Vero cells. AB - Virus specific macromolecular synthesis was studied in Vero cells infected with plaque-purified rubella virus under one-step multiplication conditions. Under these conditions, the rate of virus production was found to increase rapidly until 24 hr postinfection after which time the rate of virus production rose more slowly, reaching a peak level at 48 hr postinfection. This peak rate of virus production was maintained through 72 hr postinfection. A majority of the cells remained alive through 96 hr postinfection, although a 20 to 30% decrease in the number of living cells occurred between 24 and 48 hr postinfection, the time period at which cytopathic effect was first observed. The virus structural proteins were first detected intracellularly at 16 hr postinfection. The rate of synthesis of these proteins was already maximal at 16 hr postinfection and remained constant through 48 hr postinfection. By immunofluorescence, cells expressing virus proteins were first observed at 12 hr postinfection. At 24 hr postinfection, 35 to 50% of the cells in the infected culture were exhibiting immunofluorescence, at 36 hr postinfection, 65 to 90% of the cells were exhibiting immunofluorescence, and at 48 hr postinfection, all of the cells were exhibiting immunofluorescence. The virus genomic and subgenomic RNA species were first detectable by 12 hr postinfection. The rate of synthesis of both of these species peaked at 26 hr postinfection. Rubella virus infection was found to have no effect on total cell RNA synthesis. However, a modest inhibition of total cell protein synthesis which reached 40% by 48 hr postinfection was observed. When Northern analysis of RNA extracted from infected cells was performed, a negative polarity, virus-specific RNA probe hybridized only to the virus genomic and subgenomic RNA species. A positive-polarity, virus-specific RNA probe hybridized predominantly to a negative-polarity RNA of genome length indicating that both the genomic and subgenomic RNAs are synthesized from a genome-length negative polarity template. Defective interfering (DI) RNAs were not detected in infected cells through 96 hr postinfection or in cells onto which virus released through 96 hr postinfection was passaged. Thus, the generation of DI particles by rubella virus appears to play no role in the slow, noncytopathic replication of this virus or in the ability of rubella virus-infected cells to survive for extended periods of time. PMID- 3336945 TI - Lymphocytic choriomeningitis virus. X. Demonstration of nucleoprotein on the surface of infected cells. AB - Of a total of 17 monoclonal antibodies (MAb) directed against structural proteins of the lymphocytic choriomeningitis (LCM) virus, 3 were specific for the viral nucleoprotein (p63) and attached to the plasma membrane of infected cells, as disclosed by the indirect immunofluorescence procedure and complement-mediated cytolysis. We had previously demonstrated that a portion of the nucleoprotein (p63E) was part of the envelope of the intact virion (M. Bruns, W. Zeller, H. Rohdewohld, and F. Lehmann-Grube (1986) Virology 151, 77-85), and we now show that after external iodination of virions followed by limited proteolysis the label was attached to the smallest peptide thus obtained. If purified nucleocapsids were labeled with 125I, digested as before, and incubated with an anti-p63 MAb that has the ability to bind the surface of the infected cell, a similarly small peptide was precipitated; an antibody specific for p63 but not recognizing it on the cell surface precipitated the largest peptide and failed to bring down the small one. We conclude that the epitopes complementary to a few of our anti-p63 MAb are represented on both the virion and the surface of virus infected cells. PMID- 3336946 TI - The role of fine needle aspiration in the assessment of renal masses. AB - An investigation of the role of fine needle aspiration in the assessment of renal masses was carried out on 132 consecutive patients, 11 of whom were children. Selection was based on the presence of a solid or mixed solid and cystic renal mass that could not be defined by radiology, either in symptomatic patients or in patients to be submitted to embolization of the renal artery and at high surgical risk. Histologic and clinical data showed 49% of the cases to have a malignant, predominantly (45%) primary disease of the kidney and the remainder to have a nonneoplastic lesion. In five cases, the primary lesion was in the adrenal gland (three neuroblastomas and two pheochromocytomas). Sensitivity, specificity and predictive values for positive results were, respectively, 0.93, 0.96 and 0.935 because of a false-positive diagnosis in a case of multilocular cystic nephroma. Furthermore, in 43 of 65 cases (66%), consisting of 33 renal cell carcinomas, 1 transitional cell carcinoma, 3 Wilm's tumors, 1 neuroblastoma, 2 pheochromocytomas and 3 metastatic lesions, the histologic type could be ascertained on the tissue yielded by the fine needle aspiration. The findings stress the usefulness of this method for the clarification of radiologically not unequivocal space-occupying lesions of the renal area, especially when, in addition to the smears, histologic sections of paraffin-embedded tissues are available. Ultrastructural and immunohistochemical studies are cost-effective mainly in pediatric patients. PMID- 3336948 TI - Cirrhosis with atypia. A potential pitfall in the interpretation of liver aspirates. AB - Needle aspirations of the liver yielding highly atypical hepatocytes present a diagnostic challenge, with the differential diagnosis lying between hepatocellular carcinoma and benign reactive atypia. A case of a healing liver abscess in a patient with cirrhosis, mistakenly diagnosed as an hepatocellular carcinoma, is presented. Criteria for the avoidance of false-positive diagnoses of hepatocellular carcinoma on needle aspirates are presented, and the concept of "liver cell dysplasia" as a cytodiagnostic entity is discussed. PMID- 3336947 TI - Transthoracic needle aspiration biopsy. Review of 233 cases. AB - In 233 cases in which transthoracic needle aspiration was done at the Mayo Clinic from 1980 through 1983, the cytology slides, tissue fragments and patient histories were reviewed; the original and review diagnoses were compared and correlated with the subsequent clinical course. In most cases, the procedure was performed with an 18-gauge needle under fluoroscopic guidance, primarily in cases with suspected malignant masses that were considered to be not surgically resectable. In 70% of the cases, there was a history of malignancy, and 82% of the malignant lesions were of extrapulmonary origin. Correlation of the original diagnosis with the clinical course yielded 70% (164 cases) true positives, 6% (14 cases) true negatives, 16% (37 cases) false negatives, 0% false positives and 8% (18 cases) indeterminants. In none of the false-negative cases was the slide subsequently read as positive in a blind review. Of the true-positive cases, 12% had positive tissue fragments only, 37% had positive cytology smears only, and 51% had both positive smears and fragments. In 32% of the cases, there were radiologically demonstrable pneumothoraces, and in 12%, placement of a chest tube was required. Hemoptysis occurred in less than 5% of the cases. In summary, transthoracic needle biopsy provides an efficient way to accurately obtain diagnostic tissue, with acceptable minor complications. PMID- 3336949 TI - Cutaneous malacoplakia diagnosed by scraping cytology. PMID- 3336951 TI - Adrenal cortical carcinoma: a case diagnosed by fine needle aspiration cytology. PMID- 3336950 TI - Irradiated benign cells of the breast: a potential diagnostic pitfall in fine needle aspiration cytology. PMID- 3336952 TI - Megakaryocytes in bronchial brushings. PMID- 3336953 TI - Carpet beetle larva in cervical smear. PMID- 3336954 TI - Fine needle aspiration of the liver and pancreas with ultrasound guidance. AB - The experience of the Institut Gustave-Roussy in the diagnosis of hepatic and pancreatic lesions by fine needle aspiration (FNA) is reported. Totals of 116 consecutive percutaneous ultrasound-guided FNAs of the liver and 27 of the pancreas were performed without complication in patients with ultrasonically suspected neoplastic lesions. In 12 cases, the material was not suitable for diagnosis. In the liver, 97 cases were correctly diagnosed and confirmed by follow-up. Immunohistologic studies were helpful in distinguishing primary liver tumors from other malignancies. One false-positive result was reported. In the pancreas, malignancy was detected in 17 cases. Cytology alone provided the correct tumor diagnosis in 15 cases: 10 primary carcinomas, 2 endocrine tumors and 3 metastases. The sensitivities of FNA in this study were 87.6% for the liver and 85% for the pancreas, similar to those reported in other series. PMID- 3336956 TI - Fine needle aspiration cytopathology of phyllodes tumor. Differential diagnosis with fibroadenoma. AB - The differential diagnosis of benign or borderline phyllodes tumors of the breast in fine needle aspiration biopsy smears was studied. Smears from five histologically proven cases and 20 proven cases of fibroadenoma were evaluated with regard to their cytologic features. The findings indicate that the presence of a high cellularity of stromal fragments (including bipolar naked nuclei), clusters of hyperplastic ductal cells and giant cells and the absence of apocrine metaplasia may suggest a diagnosis of phyllodes tumor, as opposed to fibroadenoma. The borderline phyllodes tumor showed a sarcomatous atypia and/or small intranuclear cytoplasmic invaginations in some cells. The differential diagnosis of this tumor with malignant phyllodes tumor and plasma-cell mastitis is also discussed. PMID- 3336955 TI - Fine needle aspiration of the pancreas. A five-year experience. AB - Forty fine needle aspiration (FNA) biopsies of the pancreas were performed on 37 patients with a radiologic suspicion of malignancy; 32 aspirations were guided by ultrasound, 2 were guided by CT, and 6 were obtained intraoperatively. A pathologist read a rapid-stained smear of the initial aspirate as the procedure was performed and triaged specimens for routine cytologic, cell block and ultrastructural study in solid lesions plus carcinoembryonic antigen (CEA) assay and amylase study in cystic lesions. Purulent material was studied by gram staining and culture. The overall sensitivity in the series was 81%, with a specificity of 100%. No complications were noted. Ultrastructural examination improved the diagnostic accuracy in two cases. Assays for CEA and amylase in "cyst fluids" differentiated true cysts and cystadenocarcinoma from pseudocysts. Maximum utilization of the material aspirated was useful in diagnosing the etiology of solid and cystic pancreatic masses. PMID- 3336957 TI - Fine needle aspiration in stromal sarcoma of the breast. Light and electron microscopic findings with histologic correlation. AB - Stromal sarcoma of the breast, according to current concepts, is a rare lesion arising from the stroma surrounding the ductal epithelium. A case of this neoplasm is reported, with light and electron microscopic findings in fine needle aspirates and correlation with histologic findings. The findings, similar to those previously reported for stromal sarcoma of the breast, included a less pleomorphic morphologic picture than is seen in malignant fibrous histiocytoma, but a more primitive ultrastructural appearance. PMID- 3336958 TI - Perineal nodular indurations ("accessory testicles") in cyclists. Fine needle aspiration cytologic and pathologic findings in two cases. AB - The cytologic and histologic findings from two cases of perineal nodular indurations observed in two cyclists are reported. These lesions, also referred to as "accessory testicles" or "third testicle" or "ischial hygromas" of cyclists, consist of a localized aseptic area of necrosis with pseudocyst formation involving connective tissue in the superficial fascia of the perineum. These histologic findings, which were seen in the subsequent surgical specimens in these two cases, were reflected in the fine needle aspiration findings. The aspirates contained few cellular elements, mainly a few vacuolated histiocytes, against a background of fibrinous material. These indurations, which develop as a result of repeated, chronic microtrauma to the perineum impressed by the vibration of the saddle of the bicycle, constitute an authentic handicap for the professional cyclist and are a contraindication to cycling for amateur cyclists. PMID- 3336959 TI - Meningioma. PMID- 3336961 TI - AIDS packets available. PMID- 3336960 TI - Antidepressants. PMID- 3336962 TI - Pistol-packing Floridians. PMID- 3336963 TI - Organ donation. PMID- 3336964 TI - Clinical and electrophysiologic effects of amiodarone in patients with atrial fibrillation complicating the Wolff-Parkinson-White syndrome. AB - The clinical and electrophysiologic effects of oral amiodarone were evaluated in 10 patients with a history of spontaneous atrial fibrillation and a rapid ventricular response, complicating the Wolff-Parkinson-White syndrome. Five patients developed ventricular fibrillation during an episode of atrial fibrillation. Seven patients underwent electrophysiology study and arrhythmia induction, both before and during chronic amiodarone treatment. During a mean 30 months of follow-up (range 8 to 59 months), no recurrences of atrial fibrillation or ventricular fibrillation were noted. One patient had recurrent supraventricular tachycardia and underwent surgery. One had serious and five had minor side effects. Arrhythmia suppression was associated with prolongation of the anterograde accessory pathway (+38%, p less than 0.01) and atrial (+34%, p less than 0.01) effective refractory periods. Amiodarone also slowed the ventricular response to induced atrial fibrillation, prolonging the mean (+90%, p less than 0.01) and minimum (+104%, p = 0.01) R-R intervals. Thus, amiodarone is a safe and effective alternative for arrhythmia prevention if surgery is inadvisable or is not desired by the patient. PMID- 3336966 TI - Prevalence and clinical correlates of non-Wenckebach, narrow-complex second degree atrioventricular block detected by ambulatory ECG. AB - Among 113 patients with transient, narrow-complex second-degree atrioventricular (AV) block detected by ambulatory ECG, there were 20 with non-Wenckebach behavior. Based on the presence or absence of PR interval shortening after single blocked complexes, patients with narrow-complex non-Wenckebach patterns could be separated into a pseudo-Mobitz II group of 16 patients (greater than or equal to 20 msec of PR shortening after the blocked complex) and a classic Mobitz II group of four patients (constant PR interval). These groups had additional distinct ECG and clinical features. Patients with the pseudo-Mobitz II pattern had a 44% prevalence of associated Wenckebach block during the same ambulatory recording, whereas Wenckebach behavior did not occur in patients with classic Mobitz II block. Pseudo-Mobitz II block occurred at significantly longer cycle lengths (876 vs 585 msec) and with significantly longer PR intervals (225 vs 165 msec) preceding the blocked complex than did classic Mobitz II block. Syncope was the presenting symptom in 38% of patients with pseudo-Mobitz II block and in all patients with classic Mobitz II block. Patients with pseudo-Mobitz II block had a 56% prevalence of associated coronary disease and a 44% prevalence of congestive heart failure; the mortality rate was 38% in this group over 4 years of follow up, but in all instances death was due to associated disease rather than to conduction itself. In contrast, patients with classic Mobitz II block had hypertensive or valvular disease but no evidence of coronary disease or congestive failure; all are alive with pacemakers after 3 years of follow up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336965 TI - Utility of the signal-averaged electrocardiogram in patients presenting with sustained ventricular tachycardia or fibrillation while on an antiarrhythmic drug. AB - The utility of the signal-averaged electrocardiogram (SAECG) for predicting ventricular tachycardia (VT) induction in patients presenting with sustained VT or ventricular fibrillation (VF) while on an empirically chosen antiarrhythmic agent was assessed in 17 patients. At the time of presentation with a malignant arrhythmia, 12 patients were taking quinidine, three patients were taking procainamide, and two patients were taking flecainide. All patients underwent programmed ventricular stimulation when not taking antiarrhythmic drugs; 12 patients had no inducible sustained VT and five patients had inducible sustained monomorphic VT. The SAECG done in the control state without antiarrhythmic agents was negative for late potentials in 11 of 12 patients in the noninducible group and positive for late potentials in four of five patients in the inducible group (sensitivity = 80% and specificity = 92%). We conclude that in patients presenting with life-threatening ventricular arrhythmias while taking an antiarrhythmic drug, the SAECG distinguishes patients with possible proarrhythmic events from those who have the substrate for inducible sustained VT. PMID- 3336967 TI - "Irregular" ventricular parasystole: the influence of sinus rhythm on a parasystolic focus. AB - Fifteen cases of ventricular parasystole were analyzed to determine whether the interectopic intervals were regular, as expressed by long intervals being exact multiples of the short ones, or not. The regularity of the interectopic intervals was assessed by means of the variation index: the ratio of the maximal difference between various measurements of the parasystolic cycle length and the mean parasystolic cycle length. Three out of 15 cases had a variation index less than 5, and were classified as "regular parasystole." Twelve cases were associated with a variation index greater than 7.5, and were classified as "irregular parasystole." The cases of irregular parasystole were then analyzed to determine whether the variability of the interectopic intervals was casual or dependent on action of the sinus beats. A parasystolic resetting by critically timed sinus impulses (a form of intermittent parasystole) was evident in three cases. The irregularity in the remaining nine cases was due to modulation (viz., due to electrotonic influence exerted by the sinus beats on the parasystolic focus). In every case of modulated parasystole a phase-response curve was constructed, which enabled an analysis of all the interectopic intervals on the basis of a time dependent effect exerted by the sinus impulses on an otherwise rhythmic parasystolic focus. PMID- 3336968 TI - Evaluation of Bjork-Shiley prosthetic valves by real-time two-dimensional Doppler echocardiographic flow mapping. AB - We studied the value of two-dimensional Doppler echocardiographic color flow mapping for identifying normal transvalve flow profiles and valve malfunction in 20 patients with Bjork-Shiley prosthetic valves. Seven patients had Bjork-Shiley prosthetic valves in the aortic position alone, seven in the mitral position, and six had prosthetic valves in both the aortic and mitral positions. In 10 patients with normally functioning mitral valves, the ratios of the maximal major and minor Doppler-imaged orifice flow diameters to the valve ring diameters were 25 +/- 3% (mean +/- SD) and 24 +/- 3%, respectively, similar to values reported in in vitro studies. No mitral regurgitation was found in these patients by two dimensional Doppler echocardiographic flow mapping or by spectral Doppler. Of the 10 clinically normal aortic Bjork-Shiley valves, no valvular regurgitation was found by color flow mapping, whereas mild aortic regurgitation was found in two patients with the use of spectral Doppler. Malfunction of six valves was documented in five patients and was confirmed by cardiac catheterization and/or surgery. These included one case of focal fibrous ingrowth involving primarily the minor orifice of a mitral prosthetic valve, one case of mitral valve prosthetic thrombosis with decreased major and minor orifice flow diameters and valvular regurgitation, and four cases of paravalvular regurgitation involving prosthetic valves in the aortic position (three patients) and the mitral position (one patient). Two-dimensional Doppler echocardiographic flow mapping provides new observations that may aid in identifying Bjork-Shiley prosthetic valve malfunction. By localizing precisely the site of prosthetic stenosis or regurgitation, it may also assist in defining the cause of valve malfunction. PMID- 3336969 TI - Rotational atherectomy in atherosclerotic rabbit iliac arteries. AB - PTCA is not technically possible in many patients with symptoms of coronary artery disease. In addition, atheroma is not physically removed by PTCA, and restenosis of the treated vessel is common. We have tested a new, rotating, abrasive-tipped angioplasty device in vivo in 13 atherosclerotic rabbit iliac vessels. Atherosclerosis was generated in rabbit iliac vessels by a 2% cholesterol diet combined with balloon endothelial injury for 10 weeks. The diseased vessels were then treated with the rotational atherectomy device. Before treatment, contrast angiograms demonstrated that initial percent diameter stenosis was 81% +/- 9%. After atherectomy, there was significant improvement, with residual 38% +/- 22% narrowing (p less than 0.001). One perforation resulted from distal guidewire manipulation, and one vessel was occluded by the device. Histologic examination demonstrated loss of portions of the diseased intima in all cases. Particles were produced for analysis in vitro by operating the atherectomy device in atherosclerotic rabbit aortas perfused with saline solution. Ninety-eight percent of the particles produced by the device were less than 10 micron in diameter. We conclude that this new rotational device can remove atheromatous material from diseased arteries in rabbits. Such a device may complement other angioplasty techniques and lead to wider application of catheter based therapeutic interventions. PMID- 3336970 TI - Segmental evaluation of left ventricular wall motion after myocardial infarction: magnetic resonance imaging versus echocardiography. AB - To assess relative capabilities of magnetic resonance (MR) imaging and two dimensional echocardiography (2DE) for evaluating regional contractile dysfunction in the left ventricle after a myocardial infarction, results from 22 concurrent MR (orthogonal-transaxial, ECG-gated, multiphasic, single-spin echo) and 2DE examinations were compared. By means of the same 11-segment LV description, MR and 2DE examinations were independently scored segment by segment for residual wall motion (point scores: 2 = normal, 1 = hypokinesia, 0 = akinesia, and -1 = dyskinesia). Significant correlation between MR and 2DE scoring was found throughout most of the left anterior descending (LAD) distribution, but right coronary artery (RCA) distribution (i.e., middle posterior segment not well seen) could not be fully evaluated by MR imaging. When cumulative scores for the 10 segments mutually evaluated were used to derive measures of global residual LV function (i.e., score quotient [SQ] = accumulated points divided by 20 total possible points), MR SQ correlated well overall with both 2DE SQ (r = 0.82; p less than 0.05) and ejection fraction (EF) from ventriculography (r = 0.86, p less than 0.05 vs r = 0.88, p less than 0.05 for 2DE SQ compared with EF). MR evaluation of segmental wall motion was relatively stronger in the LAD distribution (MR SQ compared with 2DE SQ: r = 0.86, p less than 0.05; MR SQ compared with EF: r = 0.96, p less than 0.05) than in the RCA distribution (r = 0.06, p greater than or equal to 0.05 and r = 0.62, p greater than or equal to 0.05, respectively). For 2DE, regional variations were not as evident (2DE SQ compared with EF: r = 0.90, p less than 0.05 for LAD and r = 0.81, p less than 0.05 for RCA). For segmental evaluation of wall motion after myocardial infarction, MR imaging (transaxial, multiphasic) appears to be comparable to 2DE overall but superior in LAD distribution and inferior in RCA distribution. PMID- 3336971 TI - Bacterial endocarditis after percutaneous aortic valvuloplasty. PMID- 3336973 TI - Exercise-induced hypotension as a manifestation of right ventricular ischemia. PMID- 3336972 TI - Multiple coronary arteriocameral fistulas as a cause of myocardial ischemia. PMID- 3336974 TI - Biventricular free wall rupture with extracardiac left-to-right shunt after myocardial infarction. PMID- 3336975 TI - Four-valve endocarditis with associated right ventricular mural vegetations. PMID- 3336977 TI - Ectopic thyroid remnants within the myocardium: an unusual case of right ventricular mass. PMID- 3336976 TI - Colonic villous adenoma, polyp, and leiomyoma presenting with Streptococcus bovis endocarditis. PMID- 3336978 TI - Exclusive origin of both coronary arteries from a hypoplastic right ventricle complicating an extreme tetralogy of Fallot: lethal myocardial infarction following a palliative shunt. PMID- 3336979 TI - Factors that determine the occurrence of reperfusion arrhythmias. AB - The determinants of reperfusion arrhythmias were investigated in 63 open-chest dogs undergoing a 25-minute coronary artery occlusion followed by reperfusion. Heart rate correlated positively with the occurrence of reperfusion ventricular tachycardia (VT) and ventricular fibrillation (VF). Collateral flow during ischemia (radioactive microspheres) exhibited a strong negative correlation with the incidence of both VT and VF upon reperfusion. Importantly, a sensitive coupling was present, whereby small differences in flow were associated with large differences in rhythm disorders. The rise in intramyocardial CO2 tension (another index of severity of ischemia) was greater in dogs exhibiting reperfusion VT (p less than 0.001) and VF (p less than 0.08); however, this variable was significantly correlated with collateral flow (r = -0.57, p less than 0.01). The size of the occluded coronary bed, determined by postmortem perfusion, was not consistently related to VT; within a given range of occluded bed sizes, the incidence of VT was inversely related to collateral flow. Thus, reperfusion-induced VT is relatively independent of the size of the occluded bed, and is determined primarily by the degree of myocardial hypoperfusion. In contrast, VF did not develop with occluded beds less than 25% of the left ventricular mass; above this critical occluded bed size, its incidence was inversely related to collateral perfusion. Reperfusion VF is therefore determined by the association of a large occluded bed with a poor collateral flow. This study identifies and systematically analyzes three major determinants of reperfusion arrhythmias: (1) the severity of antecedent ischemia, estimated either from the degree of flow reduction or the rise in intramural CO2 tension; (2) the amount of ischemic/reperfused myocardium; and (3) the heart rate. In addition to conceptual interest and clinical implications, the findings have important implications for the design of future studies aimed at evaluating antiarrhythmic interventions in experimental models. PMID- 3336980 TI - Carcinoid heart disease presenting as right-to-left shunt and congestive heart failure: successful surgical treatment. PMID- 3336981 TI - Estimation of maximum oxygen uptake from clinical data: performance of the Specific Activity Scale. PMID- 3336982 TI - When "sudden cardiac death" is not so sudden: lessons learned from the automatic implantable defibrillator. PMID- 3336983 TI - Inadequate subendocardial oxygen delivery during perfluorocarbon perfusion in a canine model of ischemia. AB - Perfusion of the coronary artery distal to an occlusion was performed in 16 canine preparations to compare the mechanical perfusion of autologous blood to the perfluorocarbon fluosol DA, 20% emulsion (FDA-20). Both substances were perfused under similar conditions (30, 60, and 80 ml/min) and regional electrograms, contractility, and coronary perfusion were measured relative to native coronary perfusion. Autologous blood (60 and 80 ml/min) produced a significant increase in regional (epicardial, midmyocardial, and endocardial) and transmural flow, but not in the endocardial/epicardial perfusion ratio. No other significant changes were observed during autologous blood perfusion. In contrast, FDA-20 perfusion resulted in significant ST depression (-1.8 +/- 0.2, -1.7 +/- 0.2, and -1.3 +/- 0.3 mm) at 30, 60, and 80 ml/min, respectively. FDA-20 also induced a significant decrease in distal diastolic coronary pressure and resistance, a significant decrease in the endocardial/epicardial perfusion ratio at all three perfusion rates, and a significant reduction in delivery of O2 to the subendocardium. These results indicate that autologous blood perfusion of the distal coronary artery during occlusion preserves myocardial function to a better degree than does FDA-20. PMID- 3336984 TI - Plasma catecholamine levels in acute myocardial infarction: influence of beta adrenergic blockade and relation to central hemodynamics. AB - In a prospective study, 20 patients with acute myocardial infarction were randomly assigned in a double-blind fashion to treatment with intravenous metoprolol followed by oral metoprolol or placebo. All patients underwent hemodynamic monitoring for 24 hours. Plasma adrenaline and noradrenalin levels were estimated at baseline (mean 6.0 +/- 0.9 hours from onset of symptoms) and at 1 and 24 hours after the start of therapy. Plasma adrenaline and noradrenalin levels were elevated in all but one patient, with a further increase at 1 hour after administration of metoprolol (p less than 0.05). At baseline pulmonary capillary wedge pressure was directly related to both plasma adrenaline (r = 0.44; p less than 0.05) and noradrenalin levels (r = -0.44; p less than 0.05). There was also an inverse relationship between stroke volume index and the plasma noradrenalin level (r = -0.44; p less than 0.05) but not the plasma adrenaline level. These relationships were lost after the baseline measurements. However, between baseline and 1 hour there was a close relationship between the change in systemic vascular resistance and the changes in both adrenaline (r = -0.48; p less than 0.05) and noradrenalin levels (r = -0.66; p less than 0.01). Thus, in the early stages of myocardial infarction high plasma catecholamine levels are associated with the hemodynamic markers of severe left ventricular damage. Beta adrenergic blockade with metoprolol produced a further increase in catecholamine levels that was associated with an increase in systemic vascular resistance. PMID- 3336985 TI - Delayed myocardial ischemia following the cessation of sympathetic stimulation. AB - A phenomenon entitled "delayed myocardial ischemia" has been described, in which there is a significant degree of coronary malperfusion following the cessation of behavioral stress. The primary objective of the present study was to develop a model for the delayed ischemic response in anesthetized animals to gain insights into the underlying mechanisms. In 15 morphine and chloralose-anesthetized dogs, a moderate degree of stenosis was applied to the left circumflex coronary artery by means of a toroidal balloon occluder. The pulsed Doppler technique was used to monitor coronary flow. After baseline data were obtained, the left stellate ganglion was stimulated for 30 seconds. Heart rate increased (63%), as did systemic blood pressure (41%) and flow in the left circumflex artery (47%). These parameters rapidly returned to control levels when stimulation was terminated. Forty-five to 90 seconds later, coronary flow decreased by 65% and coronary vascular resistance increased by 45%. These hemodynamic changes were accompanied by ECG abnormalities indicative of regional myocardial ischemia. The delayed ischemic response could be prevented by pretreatment with either nifedipine (20 micrograms/kg) or prazosin (0.3 mg/kg). These data indicate that the primary mechanism for the delayed ischemic response is alpha-adrenergically mediated contraction of the smooth muscle in the coronary artery wall. PMID- 3336986 TI - Systemic alkalosis as a provocative test for coronary artery spasm in patients with infrequent resting chest pain. AB - Systemic alkalosis was used to detect coronary spasm in 237 patients with infrequent, resting, angina-compatible chest pain. The provocative test was performed without previous coronary arteriography but only in patients with negative submaximal exercise test results. Rapid infusion of alkaline solution followed by maximal hyperventilation raised arterial pH above the 7.65 value necessary for diagnostic significance in 196 (83%) patients. In 24 (12%) of these patients the provocative test induced significant ischemic ST segment changes. In all patients with a positive response, coronary artery disease, which was predominantly vasospastic (19 patients) or atheromatous with a vasospastic contribution (five patients), was demonstrated by coronary arteriography followed, if necessary, by ergot derivative injection. Chest pain and ECG changes were always reversed within 5 minutes by intravenous nitroglycerin. Coronary arteriography was not performed in all patients with a negative response; therefore, the sensitivity of the procedure could not be assessed. However, 36 patients with a negative response to hyperventilation underwent coronary arteriography; 33 (92%) had normal arteriograms and a negative response to ergot derivatives. Hyperventilation appears to be a safe and specific diagnostic procedure in a subset of patients in whom the probability of coronary artery disease may not be judged sufficient to warrant coronary arteriography as a primary diagnostic approach. PMID- 3336987 TI - Reduction in digitalis-associated postinfarction mortality with nadolol in conscious dogs. AB - Previously, we have demonstrated an increased incidence of lethal ischemic arrhythmias in postinfarction dogs with clinically observable serum digoxin concentrations, and a significant reduction in digitalis-related lethal ischemic arrhythmias after subacute left stellectomy. In the present study, the protective actions of acute beta-adrenoceptor blockade with nadolol, 1.0 mg/kg administered intravenously immediately preceding the induction of posterolateral myocardial ischemia, were assessed in conscious dogs with recent, small anterior myocardial infarctions pretreated with digoxin, 0.0125 mg/kg/day intravenously, for 5 to 7 consecutive days (total n = 11). A cohort of postinfarction dogs pretreated with digoxin alone served as a control group (total n = 26). Pre vs postdigoxin electrophysiologic testing indicated reductions in myocardial refractoriness in ventricular noninfarct and infarct zones in both treatment groups, whereas the administration of nadolol tended to reverse the reductions in ventricular refractoriness. Arrhythmia-related deaths in response to posterolateral myocardial ischemia were reduced from 12 of 20 (60%) in the digoxin control group to 2 of 10 (20%) in the digoxin + nadolol group (p = 0.039). Serum digoxin concentrations (1.29 +/- 0.14 ng/ml vs 1.39 +/- 0.24 ng/ml), underlying anterior myocardial infarct size (6.9 +/- 1.5% vs 4.6 +/- 0.9% of left ventricle), and developing posterolateral myocardial infarct size (22.8 +/- 2.5% vs 17.5 +/- 3.6% of left ventricle) did not differ significantly between the digoxin and digoxin + nadolol groups. Acute beta-adrenoceptor blockade with nadolol appears to reduce digitalis-mediated ischemic postinfarction mortality, possibly because of a salutary increase in ventricular refractoriness. PMID- 3336988 TI - Left ventricular function in ischemic mitral regurgitation--a precatheterization assessment. AB - The clinical characteristics of 150 patients with unstable ischemic heart disease were evaluated for the ability to diagnose mitral regurgitation (MR). A careful assessment of physical findings, ECG- and radionuclide-determined global and regional left ventricular function was performed in all patients to characterize the population with ischemic MR. Twenty-nine patients were found to have MR and in 65% the degree of MR was 2+ or more. All of the patients with significant MR had a systolic murmur on physical examination, and although this finding was 90% sensitive for MR it had a poor predictive value (42%). Even a characteristic apical holosystolic murmur, although specific for MR (90%), had a low sensitivity and predictive value. Two regional wall motion abnormalities (inferoposterior akinesis and apical dyskinesis with an ejection fraction less than or equal to 35%) identified 26 of 29 patients with MR and all with 2+ or more MR, as well as the 10 patients who required mitral valve replacement in addition to coronary artery bypass grafting. This finding was complementary to the results of physical examination and when used together improved the diagnostic accuracy of identifying MR. The radionuclide regurgitant index was evaluated for its predictive value in assessing MR in this group of patients but was found to be a poor discriminator in patients with abnormal ejection fractions and regional wall motion abnormalities. The precatheterization assessment of left ventricular function with radionuclide angiography can provide important insight into the presence of ischemic MR. PMID- 3336989 TI - Sustained therapeutic efficacy and safety of oral propafenone for treatment of chronic ventricular arrhythmias: a 2-year experience. AB - Thirty-two men with chronic ventricular arrhythmias responded to propafenone, a new potent antiarrhythmic agent, in short-term trials with 85% or greater reduction of total ventricular premature complexes (VPCs) per hour, 95% or greater reduction of ventricular couplets (VCs) per hour, and 100% abolition of ventricular tachycardia (VT) beats per 24 hours. These patients were continued on long-term propafenone therapy to assess sustained therapeutic efficacy and safety. Thirty patients completed 1 year and 26 patients completed 2 years of testing with this agent; one patient died of sudden death and another died of a noncardiac cause. Although there were significantly fewer patient responders at 1 and 2 years, the majority of patients (greater than 79%) continued to respond optimally to propafenone. Side effects were minor and included bitter taste, dizziness, congestive heart failure, fatigue, and significant prolongation of the PR and QRS intervals. Propafenone has sustained antiarrhythmic efficacy after 2 years without serious toxicity. PMID- 3336991 TI - Smoking: a risk factor for cardiovascular disease. Official satellite to the Third European Meeting on Hypertension. June 19, 1987, Milan, Italy. Proceedings. PMID- 3336990 TI - Efficacy of intravenous amiodarone as short-term treatment for refractory ventricular tachycardia. AB - The antiarrhythmic efficacy and safety of intravenous amiodarone were evaluated in 13 patients with recurrent sustained ventricular tachycardia. All patients had been refractory to at least three prior antiarrhythmic agents (mean, 3.3 per patient), and 11 had multiple direct current cardioversions. Intravenous amiodarone suppressed sustained tachycardia in seven patients; the concurrent use of procainamide resulted in suppression in two additional patients. Ventricular tachycardia recurred in three patients, two within 2 hours of initiation of amiodarone. Adverse effects necessitated the discontinuation of amiodarone in one patient because of significant hemodynamic deterioration. The use of intravenous amiodarone was associated with a significant fall in heart rate and cardiac output. Plasma amiodarone levels were high after initial bolus loading but declined to low or less than therapeutic levels within 60 minutes. Thus although we found intravenous amiodarone to be effective in the short-term treatment of refractory ventricular tachycardia, administration of amiodarone can be associated with significant hemodynamic deterioration. The dosing protocol used should be modified to a lower initial bolus and a higher early maintenance infusion rate. PMID- 3336992 TI - The need to manage risk factors of coronary heart disease. AB - This symposium deals with the relationship between smoking and increased risk of cardiovascular disease within a number of perspectives ranging from the biochemical to the epidemiologic. The established major risk factors for cardiovascular disease, hypertension, hypercholesterolemia, and smoking, are present, often in combination, in populations around the world. These factors have been found to interact in a synergistic manner to increase the risk of coronary heart disease. Traditional antihypertensive treatment offers little protection against coronary heart disease, perhaps because antihypertensive drugs tend to be prescribed to reduce blood pressure without attention being paid to the presence of other risk factors. This symposium should clarify new knowledge on cardiovascular risk factors, thus influencing future therapeutic strategies for hypertension and cardiovascular disease in patients who smoke. PMID- 3336993 TI - Coronary heart disease: epidemiology of smoking and intervention studies of smoking. AB - Smoking is a strong risk factor for myocardial infarction (MI) and sudden coronary death, but not for angina pectoris that is not complicated by a MI. Even light cigarette and pipe and cigar smokers run an increased risk for MI and sudden coronary death. Smoking potentiates other risk factors such as lipid abnormalities and hypertension. Smoking increases blood pressure acutely, but smokers have generally had lower blood pressures than nonsmokers in epidemiologic studies. Smoking adversely affects the prognosis in patients who have suffered a MI and those with angina pectoris. Of great importance regarding community risk of smoking are the many light and moderate smokers. These persons should be addressed more vigorously in intervention efforts. PMID- 3336994 TI - Lipid effects of smoking. AB - Cigarette smoking is believed to cause harmful cardiovascular and atherogenic effects resulting from changes in lipid metabolism. Intravenous nicotine and smoking raise plasma free fatty acid (FFA) levels through enhanced lipolysis resulting from sympathoadrenal stimulation. The study reported here investigated FFA-stimulated myocardial oxygen consumption (MVO2) in intact dogs. It was found that about half of the nicotine-induced rise in MVO2 resulted from metabolic stimulation by high concentrations of FFA, and the remainder was a result of enhanced mechanical activity of the heart directly produced by nicotine. In intact dogs, the increase in myocardial oxygen requirement resulting from excess myocardial FFA uptake also increased the severity of myocardial ischemic injury after acute coronary occlusion. Human studies with men who had smoked for more than 10 years showed that smokers had lower plasma high-density lipoprotein cholesterol fractions 2 and 3. High-density lipoprotein fraction 2 is reported to be antiatherogenic. Thus smoking appears to have at least two lipid effects that may promote coronary heart disease and atherosclerosis: increased plasma FFA and decreased plasma high-density lipoprotein cholesterol fraction 2. PMID- 3336995 TI - The Medical Research Council Hypertension Trial: the smoking patient. AB - Tobacco smoking is a powerful risk predictor for coronary disease. In the recent Medical Research Council (MRC) Hypertension Trial, which this article discusses, it also proved to be an important predictor of stroke. The MRC trial had two active treatment groups, one of which received bendrofluazide and the other propranolol. The main positive result of the trial was a 45% reduction in stroke events in the actively treated groups. Propranolol appeared to be much less effective than bendrofluazide in the prevention of stroke in smokers, although both active drugs were equally effective in nonsmokers. Possible explanations for this lack of efficacy in smokers are discussed. Coronary events were not reduced by treatment, although there was a trend toward their reduction in nonsmoking men treated with propranolol. The lack of effect of propranolol in reducing coronary morbidity and mortality rates was a surprise in view of the positive results from trials with both short-term and long-term treatment with beta-adrenergic blockade after myocardial infarction. PMID- 3336996 TI - Strategies to reduce risk factors in hypertensive patients who smoke. AB - Hypertensive patients who smoke have a high risk of developing premature cardiovascular disease. In addition to encouraging these patients to stop smoking, effective nondrug therapies include weight reduction, salt restriction, and alcohol limitation. For patients whose hypertension is severe or who have other health problems, antihypertensive drug therapy is also used. In the past, diuretics and beta-blockers have proved popular. However, these drugs have produced biochemical disturbances, such as diuretic-induced hypokalemia and both diuretic- and beta-blocker-induced alterations in blood lipids. The hazard of such drug-induced alterations may be greater in hypertensive patients, who may already suffer from hypercholesterolemia. Other drugs are available that can treat hypertension with no or beneficial influence on blood lipids. For smokers, the selective alpha 1-receptor inhibitors may be more attractive, since they also act to counteract the vasoconstriction produced by nicotine. In the future, inhibitors of hydroxymethylglutaryl coenzyme A reductase may offer potential for effective control of blood lipids in hypertensive patients who smoke. PMID- 3336997 TI - Epicardial ventricular pacemaker electrode longevity in children. AB - While epicardially implanted electrodes remain the most widely used in children for ventricular pacing, their expected longevity remains unknown. The longevity of 126 such electrodes implanted from January 1970 through December 1985 was evaluated in 81 children followed up for 1 to 192 months (median 63). Age at initial implant was 1 day to 18 years. Each child had from 1 to 5 electrodes implanted; 85 electrodes were of the sutureless helical type and 41 were of the suture-fixated type. Electrode failure, defined as loss of capture with a high pacing threshold found at operation or sensing failure, occurred in 38 electrodes from 1 to 157 months postimplant (median 37). Mode of failure was high threshold with high impedance (n = 15), low impedance (n = 6), complete inability to pace (n = 8), sensing failure (n = 2) or high threshold with no measure of impedance (n = 7). Actuarial life table analysis of electrode longevity showed a 88 +/- 3% (standard error of the estimate) survival rate at 6 months with no significant decrease until 53 months (75 +/- 5%, p less than 0.05). There was then a gradual steady decrease to 49 +/- 7% by 101 months. From 101 to 157 months no significant decrease occurred. Survival rate decrease was greatest within the first 6 month period postimplant (-12%). Electrodes surviving to 6 months are highly likely to survive until 53 months. Of those surviving to 53 months, 74% should survive to 120 months. PMID- 3336998 TI - The Activitrax rate responsive pacemaker system. AB - Bipolar Medtronic Activitrax rate responsive pacemakers were implanted in 31 patients for ventricular (28) or atrial (3) pacing. Mean follow-up was 16 months (range 10 to 26). Twenty pacemakers were implanted after catheter ablation of the His bundle, 7 for sick sinus syndrome. 1 for atrioventricular block and 3 for sick sinus syndrome with atrioventricular block. A rate response value was selected that gave a pacing rate of about 100 pulses/min during walking. Of the 31 patients, all had 24-hour ambulatory electrocardiographic monitoring with diary, 11 walked a 20-minute circuit, including a flight of stairs, and 20 had a treadmill exercise test. In 9 patients the pacing rate could be compared with the underlying sinus rate during exercise and was seen to match it very closely. In 12 patients the pacing rate during car driving was found to be similar to the sinus rate of 5 volunteers under similar conditions (mean minimum and maximum rate was 80 and 99 pulses/min, respectively). No pacing-induced arrhythmias were seen during ambulatory electrocardiographic monitoring. At high pacing rates slightly irregular pacing intervals were sometimes observed, which was due to polarization sensing. Sporadically, 1 pacing interval shortened to the upper rate value, because of a known and now resolved timing anomaly. Neither anomaly was of clinical consequence and the first could be resolved by reprogramming.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3336999 TI - Experiences with atrial pacing. AB - The records of 187 patients with permanent atrial pacemakers implanted between 1970 and 1980 were studied retrospectively to define the indications, outcome and short- and long-term complications of single-chamber atrial pacing. Pacemakers were implanted in 145 (77%) patients with tachybrady syndrome, 35 (19%) with sinus bradycardia and 7 (4%) with ventricular arrhythmia. Intact atrioventricular (AV) conduction was defined as absence of second- or third-degree heart block with incremental atrial pacing to a heart rate of 120 beats/min before implantation. The average follow-up was 30 months, including 87 patients (46%) who were followed an average of 48 months. Four patients developed significant conduction disease requiring placement of a ventricular lead. Complications included 4 lead fractures (all coronary sinus leads), 10 dislodgments (9 coronary sinus, 1 tined atrial "J") and 6 threshold rises requiring repositioning of the lead. Eight dislodgments occurred within an average of 5.6 days. The average increase in threshold that required repositioning occurred at 14 days. The average lead fracture occurred at 25 months. Atrial pacing is safe and effective for patients with sinoatrial node disorder (sick sinus syndrome) and intact AV conduction. Progression to clinically significant AV block is uncommon. Complications occur early with coronary sinus leads and are less common with newer leads. PMID- 3337000 TI - Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis. AB - A 2-part prospective study was performed to evaluate the clinical outcome of patients with hemodynamically confirmed asymptomatic valvular aortic stenosis (AS). During phase 1, linear regression analysis showed continuous wave Doppler to be highly accurate in predicting catheterization measured peak systolic aortic valve pressure gradients in 101 consecutive patients aged 36 to 83 years (mean 65 +/- 8) with symptomatic AS. During phase 2, 90 additional patients (51 asymptomatic and 39 symptomatic) with Doppler-derived peak systolic aortic valve gradients greater than or equal to 50 mm Hg (range 50 to 132 [mean 68 +/- 19]) were followed for 1 to 45 months. Both groups of patients in phase 2 had similar Doppler gradients and clinical and auscultatory evidence of moderate to severe AS at baseline. Asymptomatic patients were younger (p = 0.01), had higher ejection fractions (p = 0.001) and were less likely to have an electrocardiographic strain pattern (p = 0.01) and left atrial enlargement (p = 0.02). End-diastolic wall thickness, left ventricular cross-sectional myocardial area and estimated left ventricular mass were 18% (p = 0.0001), 20% (p = 0.0008), and 29% (p = 0.002) greater in symptomatic patients. During 17 +/- 9 months of follow-up, 21 asymptomatic patients (41%) became symptomatic. Dyspnea was the most common initial complaint, occurring 2.5 and 4.8 times more often than angina and syncope, respectively. Compared with the 39 symptomatic patients, the 51 asymptomatic patients had a lower cumulative life table incidence of death from any cause (p = 0.002), and from cardiac causes (p = 0.0001) including sudden death (p = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337001 TI - Reassessment of echocardiographic criteria for diagnosis of mitral valve prolapse. AB - Commonly used echocardiographic criteria for mitral valve prolapse (MVP) include a sizable proportion of persons whose hearts are normal. Nevertheless, the echocardiogram is generally used as an independent standard for the diagnosis of MVP despite lack of consensus on the criteria to be used and the probability of interobserver variability. Conversely, there is a relatively uniform consensus that classic auscultatory signs establish the diagnosis of MVP beyond reasonable doubt. Accordingly, in 148 patients referred for evaluation of known or suspected MVP, the echocardiographic patterns that coincide with diagnostic auscultatory signs were studied prospectively to compare those patterns with criteria commonly used for the echocardiographic diagnosis of MVP and to determine interobserver variability in echocardiographic interpretation. Eighty patients (54%) had a classic mid- to late systolic click or an apical late systolic murmur, or both. Eleven patients (7%) had the apical holosystolic murmur of mitral regurgitation with no discernible clinical or echocardiographic cause other than the consideration of MVP. Doppler echocardiography was performed in 80 of the 148 patients. The degree of superior systolic bowing of each mitral leaflet and the location of leaflet coaptation relative to the presumed plane of the mitral anulus were graded on apical 4-chamber and parasternal long-axis views. The only patterns absolutely specific for auscultatory MVP were: severe bowing of the anterior or posterior leaflet; coaptation of leaflets on the left atrial side of the anular plane; moderate to severe Doppler mitral regurgitation accompanied by any degree of leaflet bowing; and mild Doppler mitral regurgitation accompanied by moderate bowing of a leaflet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337002 TI - Accuracy of left atrial and pulmonary artery wedge pressure in pure mitral regurgitation in predicting left ventricular end-diastolic pressure. AB - In most clinical conditions pulmonary artery (PA) wedge pressure accurately reflects left ventricular (LV) end-diastolic pressure. In the presence of mitral regurgitation (MR), large V waves can distort PA wedge pressure and result in incorrect estimation of LV end-diastolic pressure. In 52 patients with MR simultaneous measurement of PA wedge pressure or left atrial pressure and LV end diastolic pressure was recorded. Twenty-one (40%) patients had large V waves (V wave greater than A wave by greater than 10 mm Hg, group 1), and 31 (60%) patients had small V waves (group 2). Group 1 had significantly higher V waves than group 2 (46 +/- 3 vs 21 +/- 2 mm Hg, p less than 0.001). The LV end diastolic pressure was similar in both groups (21 +/- 2 vs 19 +/- 2 mm Hg, difference not significant). The mean PA wedge or left atrial pressure in group 1 (26 +/- 2 mm Hg) overestimated LV end-diastolic pressure (21 +/- 2 mm Hg) by 30% (p less than 0.01), but the trough of the X descent (20 +/- 2 mm Hg) was similar to the LV end-diastolic pressure. In group 2 patients with small V waves the mean PA wedge pressure was not significantly different from the LV end-diastolic pressure (16 +/- 2 vs 19 +/- 2 mm Hg, p = 0.06), but the trough of the X descent (13 +/- 2 mm Hg) underestimated LV end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337003 TI - Prevalence and characteristics of the aortic ejection sound in adults. AB - A survey of 1,950 phonocardiograms recorded over a 6-year period revealed 170 (9%) with a distinct aortic ejection sound. All patients were men with a mean age of 61 years (range 29 to 88). Associated clinical features were: aortic stenosis in 28%, history of systemic hypertension in 10%, history of rheumatic fever in 4% and none of these features in 58% of patients. In 141 (83%) of 170 patients the aortic ejection sound occurred simultaneously with or 0.01 second before or after the onset of the rise of the externally recorded carotid pulse. In 37 (66%) of 56 patients who had simultaneous echocardiograms and phonocardiograms recorded, the aortic ejection sound occurred at 0.01 second before or after the maximal opening point of the aortic valve leaflets. Two-dimensional echocardiography was performed in all patients and a bicuspid aortic valve was identified in 38 patients (22%). In 83 patients (49%) 3 cusps were clearly seen. In 49 patients (29%) an accurate determination was not possible. Anatomic examination of 120 consecutive aortic valves at autopsy was performed to identify possible causes of the aortic ejection sound. In 18 (15%) of autopsies fusion of 2 aortic cusps extending greater than or equal to 5 mm from the attachment to the aorta was observed. This abnormality, aortic commissural fusion, may be congenital or acquired. It is concluded that aortic ejection sounds may occur in patients without bicuspid aortic valves and in a variety of clinical conditions. A moderate degree of cuspal fusion may be the cause of the sound. PMID- 3337005 TI - Usefulness of early positive technetium-99m stannous pyrophosphate scan in predicting reperfusion after thrombolytic therapy for acute myocardial infarction. AB - To test the hypothesis that scans with technetium-99m pyrophosphate (Tc-99m-PPi) are positive when performed early after successful thrombolytic therapy for acute myocardial infarction (AMI), 16 consecutive patients with AMI who received thrombolytic therapy within 5 hours after the onset of chest pain were studied. Patients were included if chest pain lasted for greater than 30 minutes, was unresponsive to sublingual nitroglycerin and was associated with at least 0.2 mV ST-segment elevation in at least 2 contiguous electrocardiographic leads. All patients received 1.5 million IU of streptokinase intravenously, a mean of 195 +/ 99 minutes after onset of chest pain. Tc-99m-PPi scans and coronary cineangiograms were recorded 491 +/- 156 minutes and 518 +/- 202 minutes, respectively, after the onset of symptoms. Effective reperfusion was present in 10 patients, 6 of whom had positive Tc-99m-PPi scans (sensitivity of 60% to detect reperfusion). Of the 6 patients without effective reperfusion, 3 had positive Tc-99m-PPi scans (specificity of 50%, p greater than 0.05). Analysis of the data using various definitions of effective reperfusion or artery patency yielded similar results. Thus, our findings indicate that early AMI scanning with Tc-99m-PPi does not accurately detect the presence or absence of reperfusion in patients with AMI after treatment with intravenous streptokinase. At this time, coronary cineangiography is the only reliable method to detect reperfusion promptly after thrombolytic therapy. PMID- 3337004 TI - Long-term prognostic significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy. AB - The prognostic significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy is controversial. Thus, 73 patients with idiopathic dilated cardiomyopathy who had both 24-hour Holter monitoring and angiography were followed for greater than or equal to 3 years. Twenty-eight patients (38%) died, 14 patients (19%) due to pump failure and 14 patients (19%) due to sudden death. Univariate analysis revealed ventricular tachycardias as a major risk indicator, among others. However, multivariate analysis determined the major independent risk factors in the following order: patients who died from pump failure, left ventricular filling pressure, left bundle branch block, the number of beats in the longest episode of ventricular tachycardia and left ventricular ejection fraction; patients who died from sudden death, left bundle branch block and left ventricular ejection fraction, but not any form of ventricular arrhythmias. Reclassification by means of the risk factors resulted in a meaningful identification of patients who died from pump failure; however, patients who died from sudden death could not be separated from survivors. Thus, in the present study Holter monitoring was unable to distinguish between patients who died from subsequent pump failure and patients who died from subsequent sudden death. PMID- 3337006 TI - Correlation of right ventricular volume using axial angulated ventriculography to known right ventricular cast volumes in infants and children with congenital heart disease. AB - To calculate right ventricular (RV) volumes from biplane cineangiography obtained in nonstandard views, regression equations were developed from RV casts of known volume. Volumes were calculated using Simpson's rule from casts ranging from 2 to 42 ml from 25 postmortem specimens with various congenital heart diseases. The casts were divided into 2 groups: group 1 (n = 15) with abnormal or group 2 (n = 10) with normal RV hemodynamic measurements. Biplane cinegrams were taken in the anterolateral, anterior and long axis oblique, hepatoclavicular and sitting up projections. The true volume of each cast was determined from its weight and specific gravity. Excellent correlations were obtained between measured and true volumes (r = 0.92 to 0.96) in all projections, although each projection overestimated the true volume (slope value less than 1). The regression equations obtained from group 1 were not statistically different from those in group 2 in any view. Although the application of different regression equations is required in measuring RV volumes by multiple angulated angiography, these regression equations appear not to be affected by the hemodynamic state of the ventricle. These results are important in assessing RV volume in pediatric patients with congenital heart disease using axial angulated ventriculography. PMID- 3337008 TI - Polymorphic ventricular tachycardia as the presenting manifestation of Bjork Shiley mitral prosthesis strut fracture. PMID- 3337007 TI - Impact of two-dimensional and Doppler echocardiography on care of children aged two years and younger. AB - To determine the impact of 2-dimensional (2-D) and Doppler echocardiography on the care of children aged 2 years and younger with suspected cardiac disease, the clinical management and outcome for the years 1975 (pre-2-D/Doppler era, 161 patients) and 1985 (2-D/Doppler era, 206 patients) were compared. Differences were: (1) decreased catheterization at our institution (48% vs 21%, p less than 0.0001); (2) trend toward decreased recatheterization of patients with referral catheterization (62% vs 38%, p = 0.08); (3) increased operation without preoperative catheterization (10% vs 37%, p less than 0.001); and (4) decreased preoperative catheterization for 7 anomalies (patent ductus arteriosus, ventricular septal defect, atrial septal defect, atrioventricular canal, aortic stenosis, tetralogy of Fallot and complete transposition of great arteries). Operative mortality rates were not statistically different in the years compared. Also, the operative mortality rates in 1985 for patients with and without preoperative catheterization were not statistically different. In 1975, cardiac catheterization changed the primary clinical diagnosis in 21%. In 1985, the primary diagnosis was not changed by catheterization; however, 2-D and Doppler echocardiography changed the diagnosis in 18%. The change in utilization of cardiac catheterization appears to be most closely related to the maximal utilization of a substitute imaging and hemodynamic modality--namely, 2-D and Doppler echocardiography. PMID- 3337009 TI - Congenital cardiomyopathy and cataracts with lactic acidosis. PMID- 3337010 TI - Double aortic arch with bilateral coarctations. PMID- 3337011 TI - Relation of results of exercise stress tests in young women to phases of the menstrual cycle. PMID- 3337012 TI - Atrial natriuretic hormone, cardiac tamponade and true filling (transmural) pressures. PMID- 3337013 TI - Comparison of high- and low-intensity exercise training early after acute myocardial infarction. AB - The effects of the intensity of exercise training on cardiorespiratory variables were investigated in a consecutive series of men with recent (median 8 weeks) acute myocardial infarction. Forty-five patients were randomly assigned either to a high- (65 to 75% maximum oxygen consumption rate [VO2max]) or to a low intensity (less than 45% VO2max) exercise group. Patients engaged in medically supervised aerobic training 3 sessions a week for 12 weeks. With training, mean VO2max significantly increased by 11% (2.09 to 2.31 liters/min) within the high group and by 14% (1.93 to 2.21 liters/min) within the low group. Differences between groups were not statistically significant. Both groups also had comparable changes in heart rate, blood pressure and double-product at submaximal and maximal workloads. Analysis of blood lipids revealed that both groups experienced a significant increase in high density lipoprotein cholesterol. There were no significant changes in total serum cholesterol or triglycerides. These findings suggest that within an unselected population of patients after acute myocardial infarction referred for cardiac rehabilitation, low- and high intensity exercise training produces relatively similar changes in cardiorespiratory variables during the initial 3 months of exercise training. PMID- 3337014 TI - Electrocardiographic manifestations and in-hospital prognosis of transient acute myocardial ischemia at rest. AB - From January 1970 to June 1985, transient electrocardiographic changes at rest were documented in 652 patients admitted to our coronary care unit. Patients were stratified according to the type of electrocardiographic alteration at rest: 295 had ST-segment elevation (group 1), 106 T-wave changes (group 2) and 251 ST segment depression (group 3). Patients in group 3, compared with groups 1 and 2, were more likely to have symptoms of coronary artery disease dating back many years (p less than 0.01 and p less than 0.01, respectively), a previous myocardial infarction (p less than 0.05 and difference not significant), a positive exercise test (p less than 0.01 and p less than 0.01), transient ST-T changes occurring in a higher number of electrocardiographic leads (p less than 0.01 and p less than 0.01), multivessel disease (p less than 0.001 and p less than 0.01) and poor ventricular function (p less than 0.01 and p less than 0.05). Despite these differences, the occurrence of acute myocardial infarction and cardiac death during hospitalization was much more frequent in group 1 compared with groups 2 (p less than 0.02) and 3 (p less than 0.05). However, death occurred in those patients who had poor ventricular function and severe atherosclerosis. A greater susceptibility of group 1 patients to severe vasoconstriction documented by the ergonovine test and by the occurrence of spontaneous spasm seems to account for different in-hospital outcome. PMID- 3337015 TI - Lack of diurnal variation in maximal symptom-limited exercise test response in chronic stable angina. AB - Exercise testing is widely used to evaluate the effects of anti-ischemic drugs. Many studies have reported good reproducibility when it is performed in the morning, but little information is available regarding the diurnal variation of exercise test response in patients with chronic stable angina. With the advent of new long-acting anti-ischemic drugs, it has become necessary to perform the exercise testing at various times of the day to determine the duration of action of a given drug. To examine the diurnal variation, exercise tests were performed on 41 patients, aged 53 to 75 years, with established chronic stable angina on 2 occasions 5 days apart at 10 A.M. and 4 P.M. on each day. On day 1, the mean +/- standard error of the mean exercise time was 5.0 +/- 0.4 minutes at 10 A.M. and 5.1 +/- 0.4 minutes at 4 P.M., and on day 5, it was 5.6 +/- 0.4 minutes at 10 A.M. and 5.5 +/- 0.4 minutes at 4 P.M. These values did not differ in statistical significance. Similarly, the time to the development of 1 mm of ST-segment depression did not show any statistically significant change during either test period on either day nor did maximal ST-segment depression. Heart rate at rest was 79 +/- 3 beats/min at 10 A.M., 81 +/- 3 beats/min at 4 P.M. on day 1 and 78 +/- 2 beats/min at 10 A.M. and 80 +/- 3 beats/min at 4 P.M. on day 5 (difference not significant). Similarly, no significant changes were observed in maximal heart rate or rate-pressure product at peak exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337016 TI - Diagnostic value for coronary artery disease of chest pain during dipyridamole thallium stress testing. AB - Intravenous dipyridamole with thallium imaging permits stress testing for coronary artery disease (CAD) without exercise. Chest pain may occur with dipyridamole-thallium testing, but its diagnostic significance is uncertain. Forty-five patients who had coronary angiography, no revascularization and chest pain during dipyridamole-thallium testing were identified. These patients were matched blindly by sex and age to 45 patients who had coronary angiography, no revascularization and no chest pain reported during the dipyridamole-thallium test. In the groups with versus without chest pain, 9 versus 24% had no CAD, 16 versus 16% had 1-vessel disease, 38 versus 29% had 2-vessel CAD and 38 versus 29% had 3-vessel CAD. These differences did not achieve statistical significance. Also, there were no evident differences in the severity of angiographic CAD by vessel or by percent of stenosis (p greater than 0.50). There was only a moderate association with ischemic ST changes (40 versus 16%, p less than 0.02). Chest pain with concurrent ischemic ST changes also failed to predict any difference in distribution or severity of angiographic stenoses. We conclude that chest pain during dipyridamole-thallium testing is not closely related to the severity of CAD and has little diagnostic value. PMID- 3337017 TI - Hemodynamic effects of alcohol at rest and during upright exercise in coronary artery disease. AB - The hemodynamic effects of acute alcohol intoxication were studied at rest and during upright exercise in 28 patients with coronary artery disease by right sided heart catheterization and radionuclide cardiography. The mean arterial blood pressure at rest was reduced by 5% and the left ventricular ejection fraction at rest decreased 2% because of end-systolic dilation during intoxication (serum ethanol 21 mmol/liter). No changes were observed in heart rate, stroke volume, pulmonary artery pressure, pulmonary artery wedge pressure or total peripheral resistance. No significant changes occurred in plasma catecholamines, and no changes occurred in any variable during mild exercise corresponding to a 30 to 40% heart rate increase. Thus, alcohol ingested in moderate doses causes slight impairment of left ventricular emptying and a reduction in the arterial blood pressure at rest in patients with coronary artery disease. A mild exercise load can be tolerated during alcohol intoxication without hemodynamic changes. PMID- 3337018 TI - Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease. AB - Dichloroacetate (DCA), which activates pyruvate dehydrogenase, has the potential to enhance carbohydrate and lactate utilization in animals, but data from patients with coronary artery disease are lacking. Accordingly, 9 patients (ages 49 to 72 years) with angina and coronary artery disease undergoing catheterization were studied. Systemic and coronary hemodynamic and metabolic measurements were made before and during DCA administration (mean dose 35 mg/kg, intravenously). DCA increased left ventricular (LV) stroke volume from 77 +/- 7 to 87 +/- 7 ml and decreased systemic vascular resistance from 1,573 +/- 199 to 1,319 +/- 180 dynes.s.cm-5 (both, p less than 0.01). There were no significant changes in heart rate, mean aortic pressure, LV end-diastolic pressure, LV dP/dt max, coronary sinus flow, coronary resistance or myocardial oxygen consumption, but myocardial efficiency index (LV work/myocardial oxygen consumption) improved from 24 to 32% (p less than 0.05). Myocardial lactate consumption was maintained (21 +/- 8 vs 19 +/- 11 X 10(-3) mEq/min, p is not significant at p less than or equal to 0.05 level) at a lower arterial lactate concentration (0.72 +/- 0.09 to 0.47 +/- 0.08 mEq/liter, p less than 0.05). DCA appears to stimulate myocardial lactate utilization at a lower arterial concentration, cause peripheral vasodilation, augment stroke volume and enhance myocardial efficiency in patients with coronary artery disease. PMID- 3337019 TI - Effects of phentolamine and atropine on angina pectoris induced by handgrip test in patients with variant angina. AB - In 19 patients with variant angina, handgrip test as an isometric exercise was performed in 3 conditions on different successive days in the early morning: in the control, after administration of phentolamine (0.3 mg/kg) and after administration of atropine sulfate (0.04 mg/kg). Angina associated with ST segment elevation on the electrocardiogram was induced in 5 patients (26%) in the control condition, in 14 (74%) after phentolamine and in 5 of 16 (31%) after atropine. All anginal events but 1 occurred after the cessation of the exercise and were not associated with the significant increase of rate-pressure products. These attacks were considered to be due to coronary spasm. The frequency of the induction of angina was significantly higher after phentolamine than in the other 2 conditions (p less than 0.01). It is concluded that the attack can be induced by the handgrip exercise in a sizable number of patients with variant angina, and that the administration of phentolamine increases the incidence of angina induced by handgrip exercise. The mechanism or mechanisms by which coronary spasm is induced by handgrip exercise remains to be elucidated. PMID- 3337020 TI - Supersensitivity of coronary arteries in variant angina to spasm induced by intracoronary acetylcholine. AB - Acetylcholine (20 to 100 micrograms) was infused directly into coronary arteries in 10 patients with variant angina (group A), 13 subjects without coronary artery disease (group B) and 8 patients with significant organic coronary artery stenosis (greater than or equal to 50%) but without variant angina (group C) during coronary arteriography, to clarify the action of this agent on coronary arteries. Temporary pacing was performed at a demand heart rate of 40 beats/min while bradyarrhythmia developed. Coronary arteriography after administration of acetylcholine showed coronary vasoconstriction in all 10 patients (100%) of group A. Angina accompanied by electrocardiographic ischemic changes in 9 of 10 (90%, 7 ST-segment elevation and 2 depression) was provoked during this test. In the patients of group B, acetylcholine also induced vasoconstriction in 8 of 22 (36%) coronary arterial systems examined, chest pain in 3 (14%) and ST-segment deviation in none (0%). In the patients of group C, acetylcholine induced vasoconstriction in 3 of 9 (33%), chest pain in 2 (22%) and ST-segment depression in 1 (11%). No definite coronary artery dilation induced by acetylcholine was noted. Coronary vasoconstriction (p less than 0.05), electrocardiographic ischemic findings (p less than 0.01) and chest pain (p less than 0.01) were induced significantly more frequently in group A than in both groups B and group C. No significant difference was found between group B and group C. The coronary arteries in the patients with variant angina seem to be more susceptible to acetylcholine than those of patients without variant angina irrespective of the presence of significant atherosclerosis. PMID- 3337021 TI - Mechanism of death and prevalence of myocardial ischemic symptoms in the terminal event after acute myocardial infarction. AB - A prospective study to determine prognostic factors for risk stratification in 867 patients surviving the coronary care unit phase of acute myocardial infarction (AMI) is reported. During a 48-month follow-up, 144 patients (17%) died. The deaths were examined for the chronology, cause, mechanism, location and presence of myocardial ischemia in the terminal event. A classification previously proposed by Hinkle and Thaler was used to define the mechanism of cardiac death and the presence of ischemia. There were 113 deaths due to coronary atherosclerotic coronary artery disease, including 5 due to complications of coronary artery bypass graft surgery. Of the remaining 108 of these deaths, 74% were classified as due to an arrhythmic mechanism and 26% as myocardial failure. Of the deaths due to an arrhythmia or to myocardial failure, 56 (52%) occurred out of hospital. The ratio of arrhythmic: myocardial failure deaths was not different for the patients who died within 3 months after the index AMI compared with later deaths. Sudden death (less than or equal to 1 hour of new symptoms) was strongly associated with arrhythmic death but 32 (54%) of patients who died greater than 1 hour after the onset of symptoms were also classified as having an arrhythmic cause of death. Previously described risk factors, including an ejection fraction less than 0.40 and greater than or equal to 10 ventricular premature complexes/hour, were independent predictors of mortality but did not differentially predict the mechanism of cardiac death. Evidence of myocardial ischemia before the terminal event was found in about 50 (60%) patients whose deaths were witnessed and who died from an arrhythmia or myocardial failure. PMID- 3337022 TI - Importance of lead selection in QT interval measurement. AB - The influence of lead selection on QT estimation in the 12-lead electrocardiogram was assessed in 63 patients (21 control subjects, 21 with anterior myocardial infarction, 21 with inferior myocardial infarction). QT estimates varied between leads. The variation was greater in patients with myocardial infarction than in control subjects (mean dispersion of QT: control subjects, 48 +/- 18 ms [+/- standard deviation]; anterior myocardial infarction, 70 +/- 30 ms; inferior myocardial infarction, 73 +/-32 ms). The maximum QT in any lead (QTmax) was determined and the deviation of each lead from this maximum value calculated. In all 3 groups, anteroseptal leads (V2 or V3) provided the closest approximation to QTmax. Interlead variability was found to be mainly due to variation in timing of the end of the T wave, rather than the onset of the QRS complex. The variability due to leads was considerably greater than the variability due to cycles, observers or measurement error. Implementation of a variety of current lead selection practices resulted in widely divergent estimates of QT interval. It is concluded that there is a need for standardization of lead selection practice for QT measurement. If measurements are confined to one or a few leads, anteroseptal leads provide the closest approximation to QTmax. PMID- 3337023 TI - Strength-interval relation for ventricular functional refractoriness. AB - Successful initiation and termination of presumed reentrant ventricular tachycardia frequently depends on the ability to deliver closely coupled impulses to the region of the tachycardia origin. To evaluate systematically the relative influence of local latency and large-scale conduction delay in limiting the delivery of closely coupled impulses, the strength-interval relation of the effective refractory period (RP), and the local and remote functional RP in 35 patients at paced cycle length of 500 ms were measured. The pacing threshold was less than or equal to 0.25 mA in all patients. The drive-train (S1) and the extrastimulus (S2) were applied from the same site, the right ventricular (RV) apex, in 25 patients, and from separate sites (RV apex and RV outflow tract) in 10 patients. The effect of procainamide (plasma concentration 10.1 +/- 2.3 micrograms/ml) on the strength-interval relations in 10 patients was also assessed. Although effective RP decreased significantly with each successive increase in current strength (p less than 0.001), local functional RP decreased only up to current strength of 4 mA, and remote functional RP decreased only up to 2 mA. Procainamide shifted the effective RP and local and remote functional RP strength-interval curves uniformly to the right without altering their relation. These data indicate that large-scale conduction delay provides the principal limitation for using increasing current strengths of a single extrastimulus to initiate or terminate ventricular tachycardia. PMID- 3337026 TI - A symposium: Arrhythmia therapy--controversies, directions and challenges. February 27-March 1, 1987, Key West, Florida. PMID- 3337024 TI - Pharmacodynamics of intravenous procainamide as used during acute electropharmacologic testing. AB - No previous studies have determined the pharmaco-dynamics of intravenous procainamide when administered in a dose of 15 mg/kg and at a rate of 50 mg/min, as is common practice during electropharmacologic testing. In this study, 30 patients received procainamide in this fashion; the right ventricular effective refractory period and the QRS duration at a ventricular pacing rate of 120/minute were then determined every minute for 20 minutes. Ten patients received no maintenance infusion of procainamide (group A), 10 received a 4 mg/min maintenance infusion (group B) and 10 received an 8 mg/min maintenance infusion (group C). Ten additional patients received no procainamide and served as control subjects (group D). The plasma procainamide concentration was measured at 1, 5, 10, 15 and 20 minutes after the loading dose was administered. A stable plasma procainamide concentration was not present in group A, B, or C until 15 minutes after infusion of the loading dose. The effective refractory period and QRS duration increased compared with baseline at 1 minute, decreased between 1 and 10 minutes and then remained essentially unchanged between 10 and 20 minutes in all 3 treatment groups. Concentration-effect relation was linear in each treatment group. The plasma procainamide concentrations in group C were significantly greater than in group A; however, the effects on refractoriness and QRS duration were similar in both groups. These findings indicate that with a procainamide dosing method commonly used during electropharmacologic testing, the plasma procainamide concentration decreases significantly during the first 15 minutes after the loading dose is administered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337025 TI - Alterations in the initial portion of the signal-averaged QRS complex in acute myocardial infarction with ventricular tachycardia. AB - This study was designed to examine 2 hypotheses: that acute myocardial infarction (AMI) alters early cardiac activation measured by signal-averaging; and that the magnitude of abnormality of early activation may be greater in patients with post AMI ventricular tachycardia (VT). We examined the root-mean square voltage amplitude in 10-ms intervals over the first 80-ms of the signal-averaged QRS complex. Data from 42 healthy volunteers were compared with those from 52 patients with previous AMI (24 anterior) but no VT and 46 post-AMI patients (33 anterior AMI) with recurrent sustained VT. Patients with VT differed from other post-AMI patients because of lower left ventricular ejection fraction, more frequent aneurysm formation and higher levels of ventricular ectopic activity. A significant decrease in initial voltage amplitude occurred at 30 to 40 ms after the beginning of the QRS in both anterior and inferior AMI patients compared with the normal group. A further significant decrease in initial amplitude occurred in VT patients both after anterior and inferior AMI. These differences persisted for the remainder of the 80-ms interval. These changes were weakly related to QRS duration (r = 0.45), ejection fraction (r = 0.50) and poorly correlated with the presence of Q waves on 12-lead electrocardiogram (r = 0.21). Direct endocardial catheter recordings performed in VT patients confirmed abnormalities of local septal activation after anterior and inferior AMI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337027 TI - Iron absorption in humans: bovine serum albumin compared with beef muscle and egg white. AB - We studied the influence of bovine serum albumin and beef meat on nonheme iron absorption in humans and on dialyzable iron in vitro. The addition of serum albumin to a maize gruel had no significant effect on nonheme Fe absorption whereas the addition of beef meat caused a threefold increase. When added to a bread meal, serum albumin caused a modest 60% increase in nonheme Fe absorption and beef meat had no effect. When added to a protein-free meal, serum albumin reduced Fe absorption by 47% compared with a 72% reduction on addition of egg white. The bioavailability of nonheme Fe from meals containing serum albumin was consistently overestimated by the in vitro technique. We conclude that the facilitation of nonheme Fe absorption by meat is not a general property of all animal protein but is better explained by the action of one or more specific animal tissues. PMID- 3337028 TI - Iron intake and iron nutritional status of infants fed iron-fortified beikost with meat. AB - We compared iron intake and iron nutritional status of two groups of healthy term infants who received meat-containing baby foods fortified with ferrous sulphate (2 mg Fe/100 g). One group received an Fe-fortified formula (1.6 mg Fe/100 kcal) and the other a nonfortified formula. Fe intake of the group fed the nonfortified formula was significantly lower (p less than 0.0001). These infants received Fe mainly from fortification Fe with beikost (75-86%) and less than 10% met the recommended intake of 1 mg.kg-1.d-1; whereas 80-85% of the infants fed the Fe fortified formula did. Hb, Hct, FEP, and ferritin were similar in both groups with the exception of lower ferritin values at age 365 d (p less than 0.05) in the group fed the nonfortified formula. No infant had hemoglobin less than 100 g/L. We conclude that regular consumption of commercially prepared Fe-fortified beikost with meat prevents most healthy term infants from Fe deficiency even if Fe intake is substantially below the recommended intake. PMID- 3337029 TI - Blood pressure response to dietary sodium restriction in healthy normotensive children. AB - To examine the effect of dietary sodium restriction on blood pressure, 149 healthy, normotensive children (64 males, 85 females) participated in a study designed to lower Na intake and maintain Na excretion at less than or equal to 75 mmol/d or half usual intake for 12 wk. Na excretion was decreased during the study period in both males (112.9 +/- 6.3 vs 53.4 +/- 3.6 mmol, p less than 0.001) and females (91.1 +/- 3.2 vs 41.1 +/- 1.9 mmol, p less than 0.001). Changes in systolic blood pressure were not significant in either sex but females showed a decrease (p less than 0.05) in diastolic and mean arterial blood pressures. Because blood pressure in children is correlated with age and body size, multiple linear regression was used to adjust blood pressure levels for age and weight. These analyses yielded small but significant decreases in systolic, diastolic, and mean arterial pressure measurements. The blood pressure response was heterogeneous but this variable response could not be attributed to varying degrees of compliance within families. These results suggest that compliance with modest Na restriction does not consistently lower blood pressure in normotensive children. PMID- 3337030 TI - Compositional changes in plasma high-density lipoprotein particles in marginally zinc-deficient male rats. AB - This study investigated the effect of zinc status on the lipid and apolipoprotein composition of high-density lipoproteins (HDL) in adult male rats fed a semipurified diet containing a marginal level (2.8 mg/kg) of Zn as compared with the pair-fed and ad libitum-fed controls given an adequate level (30.8 mg/kg) of Zn for 7-10 wk. Compositional and chromatographic analysis of HDL fraction showed that Zn deficiency significantly lowered the total amount of circulating HDL particles with no effect on the concentrations of total protein, triglyceride, phospholipid, and cholesterol. The ratios of free: esterified cholesterol remained the same for the three groups. Electrophoretic analysis of the apolipoprotein profile showed marked decreases in the relative contents of apolipoproteins E and C and an increase in apolipoprotein (apo) A-I with no significant change in apo A-VI. No apparent morphologic aberrations of HDL particles were observed. Such changes may significantly influence the transport and metabolism of cholesterol and may provide an explanation for altered cholesterol homeostasis in Zn deficiency. PMID- 3337031 TI - Impact of infection on the growth of children from 0 to 2 years in an urban West African community. AB - To determine the relationship between growth and morbidity in the first 2 y of life, we studied a cohort of 126 newborns in a Gambian township. Mean weight-for age exceeded the National Center for Health Statistics (NCHS) standards in the first half of infancy but there was a mean deficit of 1.2 kg by age 1 y. Only two diseases contributed significantly to weight faltering: diarrheal diseases were estimated to cause one-half of the deficit and lower respiratory tract infections (LRTI) one-quarter. LRTI reduced weight gain in young children by 14.7 g/d of infection and diarrheal diseases in weaning infants by 14.4 g/d. Diarrhea had no significant impact on the growth of exclusively breast-fed infants. Growth velocity was normal in the second year of life, despite continuing infections. PMID- 3337032 TI - Alcohol consumption and nutrient intake in middle-aged Scottish men. AB - The relation between alcohol consumption and dietary intake was examined in 164 middle-aged Scottish men taking part in a study of risk factors for coronary heart disease (CHD). A 7-d weighed dietary record was used to assess alcohol and nutrient intake. The mean daily intake of alcohol was 26 g (SD 31 g). Energy derived from alcohol tended to replace energy derived from other nutrients and increasing intake of alcohol was associated with a decrease in the amounts of carbohydrate, total fat, and saturated and monounsaturated fatty acids in the diet. Those with a low alcohol intake (0.1-9 g alcohol/d) had a higher intake of total fiber, cereal fiber, polyunsaturated fatty acids, and linoleic acid and a smaller proportion smoked cigarettes. The differences are small but may contribute to the lower mortality from CHD reported by other studies in those with a low alcohol intake. PMID- 3337033 TI - Effect of acute caloric restriction on work efficiency. AB - Whether caloric restriction can alter the efficiency of muscular work raises important questions regarding the control of energetic coupling processes and the efficacy of exercise as a treatment for obesity. To address these issues, oxygen uptake (VO2) was determined at rest and during incremental cycle ergometry in 13 moderately obese (133 +/- 3% ideal body weight, means +/- SEM) women during weight maintenance and after 3 wk of caloric restriction (800 kcal/d). Work efficiency was calculated from the linear portion of the VO2-work rate relationship. Caloric restriction decreased body weight 4.0 +/- 0.4 kg (p less than 0.05), VO2 at rest 32 +/- 3 mL/min (p less than 0.05), and VO2 during unloaded (0 W) cycling 47 +/- 14 mL/min (p less than 0.05). However, work efficiency was unchanged (ie, -0.3 +/- 1.2%, NS). We conclude that, despite metabolic adaptations resulting in decreased energy expenditure at rest and during zero Watt cycling, acute caloric restriction does not alter work efficiency. PMID- 3337034 TI - Nitrate, nitrite balance, and de novo synthesis of nitrate. PMID- 3337035 TI - The 120-year diet. PMID- 3337036 TI - Dietary carbohydrates in the prevention and treatment of metabolic diseases. PMID- 3337038 TI - Oxygen uptake and energy output during walking of obese male and female adolescents. AB - Oxygen uptake and steady-rate energy output of 7 obese male and 13 obese female adolescents (greater than 178% ideal body weight) walking at four different speeds (1.167, 1.5667, 1.7833, and 2.125 m/s) were studied. Body composition was measured by hydrostatic weighing, and steady-rate energy output by open circuit spirometry. Energy output was expressed as kJ/min (kcal/min) and indexed to body mass and fat-free mass. A 2-by-4 ANOVA (sex by speed) revealed significant differences in the energy output between the speed conditions. There was no significant difference between the sexes. A nonlinear increase in calorie output with increasing speed indicated a decreasing efficiency with increasing speed of walking. Possible reasons include biomechanical factors such as increased upper body forward lean needed to maintain balance at faster speeds of movement, increased energy output due to increased inertia, extra energy output needed to accelerate the limbs and torso, and increased body fat. PMID- 3337039 TI - Carotenoid and tocopherol composition of human adipose tissue. AB - Concentrations of individual carotenoids and tocopherols were determined in abdominal adipose tissue from 19 adults undergoing corrective surgery. Samples were extracted and saponified before separation and quantitation of carotenoids and tocopherols by reverse-phase high-performance liquid chromatography. Total carotenoid concentration varied 40-fold between individuals, from 0.34 to 13.51 micrograms/g adipose tissue. Beta-carotene and lycopene were the predominant carotenoids, averaging 20.2 and 18.5% of total carotenoids, respectively. In 10 of 19 subjects, the lycopene concentration exceeded that of beta-carotene. Total tocopherol concentrations varied 11-fold, with alpha-tocopherol representing 80.6 +/- 8.1% of the total. Absolute concentrations of both carotenoids and tocopherols were more variable than their relative concentrations. Both beta carotene and lycopene concentrations were highly correlated with total carotenoid content but there was no correlation between beta-carotene and lycopene or between beta-carotene and alpha-tocopherol concentrations. PMID- 3337037 TI - Resistance weight training during caloric restriction enhances lean body weight maintenance. AB - To assess the individual and combined effects of weight loss and weight training on body weight and body composition, 40 obese women were randomly assigned to one of four groups for an 8 wk weight-loss study. These groups were control (C); diet without exercise (DO); diet plus weight training (DPE); and weight training without diet (EO). Body weight decreased for DO (-4.47 kg) and DPE (-3.89 kg) compared with C (-0.38 kg) and EO (0.45 kg). Lean body weight (LBW) increased for EO (1.07 kg) compared with DO (-0.91 kg) and C (-0.31 kg) and for DPE (0.43 kg) compared with DO. Upper-arm muscle areas (determined by radiograph) increased for DPE (11.2 cm2) and EO (10.4 cm2) compared with C (2.7 cm2) and DO (2.1 cm2). It was concluded that weight training results in comparable gains in muscle area and strength for DPE and EO. Adding weight training exercise to a caloric restriction program results in maintenance of LBW compared with DO. PMID- 3337040 TI - Starch absorption by healthy man evaluated by lactulose hydrogen breath test. AB - The amounts of hydrogen produced from starch and lactulose were compared to assess the accuracy of the hydrogen breath test with lactulose as standard to quantify starch malabsorption. The mean amounts of hydrogen produced from starch and lactulose were not different in fecal homogenates and in breath excretion after carbohydrate infusions into the cecum. Known amounts of starch infused into the cecum of 18 subjects were compared with amounts calculated from the total excess excretion of hydrogen in breath computed in relation to hydrogen production after the ingestion of 10 g lactulose; calculated amounts were 3.6 +/- 1.0, 9.9 +/- 1.3, and 22.0 +/- 3.4 g for the infusion of 5, 10, and 25 g of starch, respectively. The lactulose hydrogen breath test based on total excess hydrogen volume provides a valid measurement of the mean amount of starch metabolized in the colon in a group of subjects. However, large individual variations preclude its use in a given subject. PMID- 3337041 TI - Lean body mass estimation by bioelectrical impedance analysis: a four-site cross validation study. AB - This study validated further the bioelectrical impedance analysis (BIA) method for body composition estimation. At four laboratories densitometrically determined lean body mass (LBMd) was compared with BIA in 1567 adults (1069 men, 498 women) aged 17-62 y and with 3-56% body fat. Equations for predicting LBMd from resistance measured by BIA, height, weight, and age were obtained for the men and women. Application of each equation to the data from the other labs yielded small reductions in R values and small increases in SEEs. Some regression coefficients differed among labs but these differences were eliminated after adjustment for differences among labs in the subjects' body fatness. All data were pooled to derive fatness-specific equations for predicting LBMd: the resulting R values ranged from 0.907 to 0.952 with SEEs of 1.97-3.03 kg. These results confirm the validity of BIA and indicate that the precision of predicting LBM from impedance can be enhanced by sex- and fatness-specific equations. PMID- 3337042 TI - Increased urinary methylmalonic acid excretion in breast-fed infants of vegetarian mothers and identification of an acceptable dietary source of vitamin B-12. AB - Increased urinary methylmalonic acid (UMMA) concentrations might indicate vitamin B-12 deficiency. Our study tested the hypothesis that elevated UMMA in breast-fed infants is associated with decreased maternal serum B-12 concentrations. UMMA concentrations were measured in 17 vegetarian mothers and their infants and in six infants of nonvegetarian mothers. Serum vitamin B-12 concentrations were determined in all mothers. Range of UMMA for vegetarian infants (3-924 mcg/mg [2.6-790.9 mumol/mmol] creatinine) was much broader than that for omnivorous infants (2-25 mcg/mg [1.7-21.4 mumol/mmol] creatinine). Maternal UMMA and serum vitamin B-12 were negatively correlated (r = -0.700, p = 0.003). Infant UMMA concentrations correlated positively with maternal UMMA concentrations (r = 0.686, p = 0.003) and inversely with maternal serum vitamin B-12 concentrations (r = -0.681, p less than 0.001). In three infants with high UMMA concentrations, vitamin B-12 treatment (oral B-12, vitamin B-12 injection, or a modification of maternal diet within the vegetarian philosophy) led to an abrupt decrease of UMMA. PMID- 3337043 TI - Calcium absorbability from milk products, an imitation milk, and calcium carbonate. AB - Whole milk, chocolate milk, yogurt, imitation milk (prepared from dairy and nondairy products), cheese, and calcium carbonate were labeled with 45Ca and administered as a series of test meals to 10 healthy postmenopausal women. Carrier Ca content of the test meals was held constant at 250 mg and subjects fasted before each meal. The absorbability of Ca from the six sources was compared by measuring fractional absorption by the double isotope method. The mean absorption values for all six sources were tightly clustered between 21 and 26% and none was significantly different from the others using one-way analysis of variance. We conclude that none of the sources was significantly superior or inferior to the others. PMID- 3337044 TI - Adverse effects of high dietary iron and ascorbic acid on copper status in copper deficient and copper-adequate rats. AB - The effects of elevated dietary ascorbic acid and iron on copper utilization were examined. Male Sprague-Dawley rats were fed one of two levels of Cu (deficient, 0.42 microgram Cu/g, or adequate, 5.74 micrograms Cu/g), Fe (moderate, 38 micrograms Fe/g or high, 191 micrograms Fe/g), and ascorbic acid (low, 0% or high, 1% of the diet) for 20 d. High Fe decreased (p less than 0.05) Cu absorption only in Cu-deficient rats. High ascorbic acid significantly decreased tissue Cu levels in Cu-adequate rats. High Fe with ascorbic acid caused severe anemia in Cu-deficient rats and decreased plasma ceruloplasmin by 44% in Cu adequate rats. Cu,Zn-superoxide dismutase activity in erythrocytes was decreased (p less than 0.05) by 14% during Cu deficiency but was not affected by Fe or ascorbic acid. These results may be important to individuals with high intakes of Fe and ascorbic acid. PMID- 3337045 TI - Relapse of intermediate or high-grade (unfavorable) non-Hodgkin's lymphoma as a low-grade (favorable) Non-Hodgkin's lymphoma. Report of four cases. AB - The authors present four cases of low-grade (favorable) non-Hodgkin's lymphoma appearing after successful treatment of intermediate or high-grade (unfavorable) non-Hodgkin's lymphoma. In each case, the patient had intermediate or high-grade non-Hodgkin's lymphoma, received multiagent chemotherapy, and entered complete remission lasting one to six years. Each patient had a relapse with low-grade non Hodgkin's lymphoma. Possible explanations and therapeutic implications are discussed. PMID- 3337046 TI - Coloration of breast fluid related to concentration of cholesterol, cholesterol epoxides, estrogen, and lipid peroxides. AB - The coloration of nipple aspirates of breast fluid from 2,343 women were compared with breast fluid concentrations of cholesterol. cholesterol epoxides, lipid peroxides, estrogens, and immunoglobulins. Darker-colored breast fluid had significantly higher mean concentrations of cholesterol, cholesterol epoxides, lipid peroxides, and estrogens than did lighter-colored fluids, whereas no relationship of coloration with immunoglobulin levels was found. PMID- 3337047 TI - Guidelines for the presentation of research in the written form. PMID- 3337048 TI - The relationship of intralaboratory bias and imprecision on laboratories' ability to meet medical usefulness limits. AB - The previously described computer modeling technic empirically develops quantitative relationships between intralaboratory performance, as characterized by individual laboratories' coefficients of variation (CVs) and biases, and clinical "medical usefulness limits." These limits determine the magnitude of total analytic error, the combined effects of CV and bias that can be tolerated by the clinician. The computer model delineates all combinations of CV and bias compatible with specified medical usefulness limits. Both CV and bias are critical in determining a laboratory's ability to meet medical usefulness limits. For example, a laboratory with a 6% CV and zero bias will meet the +/- 10% or less total analytic error (medical usefulness limit) 90% of the time. If the medical usefulness limit is expanded to +/- 15%, a laboratory with a 6% CV can tolerate coexisting relative biases of up to 4% and still meet this limit 95% of the time. Plots of the limiting values for combinations of intralaboratory CV and bias are given that allow the laboratory's results to fall within medical usefulness limits of 2, 5, 10, 15, and 20%. PMID- 3337049 TI - The variations between heparin sensitivity of different lots of activated partial thromboplastin time reagent produced by the same manufacturer. AB - The variations between different lots of activated partial thromboplastin time (APTT) produced by three major North American suppliers were evaluated over the past eight years. The authors found significant variations between the heparin sensitivity of the APTT reagents produced under the same name by the same supplier. The variations were so much that, using the recommended APTT ratio or prolongation of APTT for monitoring heparin therapy, one would have achieved significantly different intensity of heparinization from year to year. PMID- 3337050 TI - Comparison of nuclear DNA content in primary and metastatic differentiated thyroid carcinoma. AB - Nuclear DNA content of 20 cases of primary differentiated thyroid carcinoma, 27 corresponding cervical lymph node metastases, and 2 local recurrent tumors was determined by flow cytometry. Evidence of DNA aneuploidy was found in either the primary tumor or in the corresponding metastases in 10 (63%) of the 16 papillary carcinomas, in all 3 follicular carcinomas, and in the case of medullary carcinoma studied. In all but one case, the aneuploid stemlines found in the regional metastases were also found in the primary or in the recurrent tumor. In four cases diploid metastatic tissue was found to originate from a tumor with DNA aneuploidy, and in three other cases two stemlines of tumor cells with different DNA indices could be shown in the primary tumor, further indicating clonal heterogeneity in differentiated thyroid carcinomas. None of the 11 patients with either diploid or aneuploid primary tumor with a DNA index less than 1.2 evaluated for 4-12 years died from thyroid cancer, whereas 5 of the 7 patients with primary tumor DNA index greater than 1.2 died from thyroid cancer (P less than 0.01). PMID- 3337051 TI - Differential lectin staining of central and peripheral zones of the prostate and alterations in dysplasia. AB - Histochemical staining with a battery of ten lectins demonstrated differences in lectin binding patterns between seminal vesicle, prostatic central and peripheral zones, and foci of prostate intraductal dysplasia, a putative premalignant lesion. Lectin binding patterns of seminal vesicle and central zone of the prostate were identical except for a single lectin, supporting the concept that these two structures have a common embryologic origin from the wolffian duct. Three of the lectins that bound to central zone were not bound in peripheral zone, indicating a biologic difference between these two regions of the prostate. Dysplasia foci showed markedly reduced binding with all lectins, consistent with impaired processing of glyco-conjugates. Lectin binding patterns appear to have value as sensitive markers of differences in terminal differentiation of closely related tissues and of early impairment of differentiated function in lesions that are precursors to carcinoma. Specific patterns of lectin binding provide information on the differential carbohydrate composition of the regions of the prostate. PMID- 3337053 TI - The thrombin clotting time. Evaluation of Thromboquik, a commercial thrombin reagent, and observations on sensitivity and on centrifugation. AB - The thrombin clotting time (TCT) is an important screening test of coagulation, but thrombin can be a troublesome reagent to use, and in general the TCT has not been well standardized, even with respect to the ideal normal range. Thromboquik is a thrombin reagent that is convenient in its day-to-day use and that exhibits prolonged stability after reconstitution. As an extension of an evaluation of this commercial thrombin reagent, the authors have made several observations about the TCT itself. In a comparison between multiple pairs of TCT reagents, the relative extent of departure of clotting times from normal, for any given abnormal plasma sample, was not predictably related to the mean normal clotting times of the two reagents. The authors also concluded that centrifugation of blood at 1,500 X g is inadequate to prepare plasma for the TCT. PMID- 3337054 TI - Fecal fat concentrations and pancreatic steatorrhea. PMID- 3337052 TI - Marrow fibrosis and multiple myeloma. AB - A retrospective review of pretreatment bone marrow material from 297 patients diagnosed and treated for multiple myeloma (MM) at a single institution during a 22-year period (1961-1982) was performed in order to assess the frequency and significance of associated simple marrow fibrosis (SMF). The presence of SMF was suspected in the hematoxylin and eosin-stained sections in 48 of the 297 cases and was confirmed by reticulin stains in 26 (8.8%) cases, with seven of these also showing collagen on trichrome stain. However, the literature on MM documents little recognition of this association. SMF is often responsible for inadequate marrow aspirates yielding spurious or inconclusive results. Thus, bone marrow trephine biopsies may be required to histologically confirm the diagnosis of MM when there is concurrent SMF. PMID- 3337055 TI - Invasive candidiasis following cimetidine therapy. PMID- 3337056 TI - Primary upper aerodigestive tract manifestations of gastroesophageal reflux. AB - Chronic hoarseness, chronic sore throat, "lump in the throat," or cervical pain with swallowing were the primary complaints in 25 (6.6%) of 379 patients undergoing esophagoscopy for gastroesophageal reflux at the Denver Veterans Administration Medical Center between 1981 and 1985. In 18 (72%) of the 25 patients, these were the only reflux symptoms. Surgery was required to control symptoms in nine (36%) patients with upper aerodigestive tract complaints, versus 52 (15%) of 354 patients with more typical reflux symptoms (z = 2.77, p less than 0.01). Surgery was also necessary more often in patients with chronic hoarseness or sore throat (seven of 15) than in those with "lump in the throat" or cervical pain with swallowing (two of 10). These findings suggest reflux does cause otherwise unexplained upper aerodigestive tract symptoms, and that surgery may be required more often to control these symptoms than is the case in patients with more typical symptoms of reflux. PMID- 3337057 TI - The epidemiology of malignant neoplasms of the stomach in Canada during the period 1931-1984. AB - Morbidity patterns in Canada for malignant neoplasms of the stomach were examined for the period 1970-1980 and mortality patterns for the period 1931-1984. Age standardized morbidity rates (ASMR) have declined significantly in males (p = 0.011) and females (p = 0.0011) during the period studied by, on average, 0.20 fewer new cases per 100,000 population per yr. The significant declines in ASMRs are attributable to significant declines in age-specific rates for males aged 35 44 (p = 0.013) and 55-64 (p = 0.046) and females aged 55-64, 65-74, and 75-84 yr (p less than 0.015). Significant declines in age-standardized death rates (ASDR) have also occurred in both males and females (p = 0.0001), with 15 of the 16 age sex groups studied showing significant rates of decline (p less than 0.0005). The greatest rates of decline were noted for males and females aged 75-84, where age specific rates have declined by more than 4.2 deaths per 100,000 population per yr since 1931. PMID- 3337058 TI - Study of the secretion of pepsinogen I in cirrhotic humans with and without portacaval shunt. AB - Thirty-nine subjects have been studied: 14 with hepatic cirrhosis who had not been subjected to surgery, 13 cirrhotic patients in whom portacaval shunt had been performed, and 12 normal controls. In all of them, we performed serum determinations of pepsinogen I, both basal and after pentagastrin stimulation, and of basal gastrin levels, as well as analyses of basal and stimulated gastric acid secretion (basal acid output and maximal acid output). The values for pepsinogen I, basal or post-stimulation, were higher (p less than 0.001) in patients with cirrhosis who had not undergone surgical shunt than in those in the control group. However, there were no statistically significant differences when these two groups were compared with the patients who had been subjected to portacaval shunt. In this last group of patients, seven had levels similar to those of the controls, and six presented higher values. Likewise, the values for gastric acid secretion were similar in the three groups of patients, and the basal gastrin level was lower (p less than 0.001) among patients with liver cirrhosis, whether or not they had undergone surgery, than among the control population. In conclusion, the functional alterations of the gastric mucosa in patients with hepatic cirrhosis are not significantly different from those found in cirrhotic patients with portacaval shunt. PMID- 3337060 TI - Direct cholangioscopy and pancreatoscopy at time of endoscopic retrograde cholangiopancreatography. PMID- 3337061 TI - The place of oral 5-aminosalicylic acid in the therapy of ulcerative colitis. PMID- 3337059 TI - Familial granulomatous hepatitis: a hitherto unrecognized entity. AB - Two West Indian parents and three of their seven offspring presented over a 12-yr period with identical systemic illnesses characterized by the development of granulomatous hepatitis. Granulomata were variably also found in muscle, lymph nodes, and pleura in some of these affected individuals. The usual causes of granulomatous hepatitis were absent, and this familial disease represents a hitherto undescribed entity. PMID- 3337063 TI - Polystyrene bezoar in a patient with polystyrenomania. AB - A 35-yr-old man with hematemesis, epigastric pain, and no predisposing factors to delayed gastric emptying was found to have a gastric bezoar. Surgical removal was required. Pathological and biochemical examination revealed a mass composed of polystyrene. This represents an unusual composition and a newly recognized predisposing factor to bezoar formation, "polystyrenomania" from ingestion of styrofoam cups. PMID- 3337062 TI - Sucralfate therapy for lye-induced esophagitis. AB - Sucralfate is a recently introduced drug that has received acceptance as a nonsystemic, locally active antiulcer agent used in the treatment of duodenal ulcer disease. In addition, sucralfate has been used for the treatment of gastric ulcer and a variety of other gastrointestinal diseases. However, the use of sucralfate to treat caustic esophagitis has not been clinically investigated, and a review of the literature yielded scant information (1). Herein, we report our experience with sucralfate in the treatment of a case of lye-induced esophagitis. PMID- 3337065 TI - Subclinical portal-systemic encephalopathy. PMID- 3337066 TI - Acute brucella ileitis. AB - Human brucellosis is an enteric fever in which systemic symptoms are generally more prominent than gastrointestinal complaints. During an outbreak of infection caused by Brucella melitensis, linked to ingestion of unpasteurized goat milk cheese, we treated a child with radiographic evidence of acute ileitis. Alimentary tract involvement in brucellosis is reviewed. PMID- 3337064 TI - Obstructing plasmacytoma of the duodenum: first manifestation of relapsed multiple myeloma. AB - A patient with an obstructing, annular duodenal neoplasm is described. Percutaneous fine needle aspiration biopsy, and biopsy performed through an endoscope, confirmed that the lesion was an extramedullary plasmacytoma. The patient had been in clinical remission from multiple myeloma for the preceeding 13 months. Radiation therapy resulted in cessation of symptoms including gastrointestinal blood loss. After 5 months, recurrent obstructive symptoms and melena led to surgical extirpation of the tumor, with relief of all symptoms. PMID- 3337067 TI - Collagenous colitis. AB - A middle-aged female with chronic, watery diarrhea was diagnosed after extensive evaluation as having collagenous colitis. The clinical, histological, and pathological findings of our case and those previously reported are reviewed. The diagnostic importance of total colonoscopy with biopsy in a normal-appearing colon in a patient with chronic, undiagnosed, watery diarrhea is discussed. PMID- 3337068 TI - Recurrent acute pancreatitis associated with pancreas divisum. AB - Described is the case of a 24-yr-old patient in whom recurrent attacks of acute pancreatitis following a cholecystectomy were found to be associated with anomaly of the pancreas--the so-called pancreas divisum. An examination by endoscopic retrograde cholangiopancreatography showed typical findings of a short duct of Wirsung. Cannulation of the secondary duct of Santorini revealed a grossly dilated and strictured duct full of stones. After drainage of the duct by a pancreaticojejunostomy (Puestow procedure), the patient has not had any further episodes of acute pancreatitis during a follow-up period of 4 yr. PMID- 3337069 TI - Primary mesenteric liposarcoma. AB - Primary mesenteric liposarcomas (PMLs) are rare neoplasms, with a review of the English literature revealing only 10 cases. This paper describes an additional case of PML, and collates the currently documented cases, thus creating the framework for delineating the profile of this neoplasm. It is a tumor of adults that has characteristic clinicopathological and radiological features. In contradistinction from the retroperitoneal liposarcoma, the PML is eminently resectable, and requires aggressive surgical management. PMID- 3337070 TI - A case of liver cirrhosis with large portacaval shunt from the superior mesenteric vein: normalization of reversed portal blood flow with medical treatment. AB - A case of liver cirrhosis with large portacaval shunt from the superior mesenteric vein is reported. The portal blood flow was diagnosed as reversed on admission, but normalized with treatment. Blood flow was measured noninvasively and repeatedly using an ultrasonic Doppler duplex system. The reversed portal flow led to the superior mesenteric vein, right (and some left) internal inguinal vein, and inferior vena cava. This rare collateral pathway was clearly demonstrated by percutaneous transhepatic portalgraphy. A link between shunt and an appendectomy carried out 22 yr ago is considered, and the possibility of the temporarily reversed portal blood flow on admission being due to deteriorated hepatic hemodynamic conditions is discussed. PMID- 3337071 TI - Risk in childhood of development of severe adult obesity: retrospective, population-based case-cohort study. AB - Recent studies have shown a weak continuity of fatness from childhood through adulthood within the central part of the population distribution. This study presents body mass index values (weight/height2) from ages 7-13 years for the 429 severely obese young males with a body mass index of at least 31 kg/m2 among 93,800 draftees born between 1930 and 1956 inclusive who attended school and underwent draft board examination in Copenhagen. This group was compared with a random 1% sample from the same draftee population. At age seven years, the obese group already had a much higher body mass index than did the population sample, and the deviation increased as the children grew older. The risk of becoming a severely obese adult increased exponentially over the entire range of body mass index in childhood. Logistic regression analysis showed that 13-year-old overweight children who had either decreased or increased in percentile level since age seven years had a higher risk of developing severe adult obesity than did 13-year-old children who had maintained their percentile level. However, most obese children did not develop severe obesity in adulthood, and only a few had been severely obese throughout. PMID- 3337072 TI - Ethnic differences in hip fracture: a reduced incidence in Mexican Americans. AB - To confirm a previous report of lower risks of hip fracture in Mexican Americans, we calculated the incidence of hip fractures among Hispanics, blacks, and non Hispanic whites residing in Bexar County, Texas, during 1980. A total of 576 residents with hip fracture not due to severe trauma were identified. The 1980 census data were used to calculate ethnic-specific incidence rates which were age adjusted using the entire 1980 US population as the standard. Hip fractures were more common among non-Hispanic white women (139 per 100,000; 95% confidence interval (CI) = 124-153) than among Mexican-American (67 per 100,000; 95% CI = 51 82) or black (55 per 100,000; 95% CI = 27-83) women. Thus, Mexican Americans and blacks are relatively protected from hip fractures, and they may benefit less than whites from prophylactic therapies for osteoporosis. PMID- 3337074 TI - Re: "Long-term risk of hysterectomy after tubal sterilization". PMID- 3337075 TI - Re: "Sex hormone levels in serum in relation to the development of breast cancer". PMID- 3337073 TI - The use of a self-administered questionnaire to assess diet four years in the past. AB - The use of a mailed, self-administered, semiquantitative food frequency questionnaire to describe past dietary intake was evaluated in 1984 among a group of 150 Boston-area women who had completed four one-week diet records three to four years previously. Correlation coefficients comparing calorie-adjusted nutrient intakes computed from the questionnaire with those obtained from a compressed version of the questionnaire completed during diet record keeping ranged from 0.44 for total carbohydrate to 0.62 for vitamin C including supplements. Coefficients comparing calorie-adjusted nutrient intakes measured by questionnaire with those assessed by the diet records completed three to four years previously ranged from 0.28 for iron without supplements to 0.61 for total carbohydrate. An evaluation of the incremental contribution provided by several open-ended sections of the questionnaire to the estimation of nutrient intake suggested that in this population most of these items might be eliminated without material loss of information. These findings demonstrate that useful estimates of nutrient intake several years previously can be obtained by a relatively inexpensive, mailed, self-administered questionnaire. PMID- 3337076 TI - Re: "Case-control study of lung cancer in civilian employees at the Portsmouth Naval Shipyard, Kittery, Maine". PMID- 3337077 TI - Case-control study of lung cancer in civilian employees at the Portsmouth Naval Shipyard, Kittery, Maine. AB - Case-control analysis of deaths due to lung cancer (International Classification of Diseases, Eighth Revision, code 162) among persons who worked at the Portsmouth Naval Shipyard, Kittery, Maine, between 1952 and 1977 found elevated odds ratios for exposures to ionizing radiation, asbestos, and welding byproducts. The radiation-related excess was statistically significant in persons with cumulative lifetime exposures of 1.0-4.999 rem. When asbestos and welding histories were combined into a single risk factor, odds ratios for the combined exposure were significantly elevated for two of three duration-of-exposure categories examined. Further analysis of data on radiation exposure, controlling for exposures to asbestos and welding, found reductions in initial estimates of radiation risk at all levels of radiation exposure. This reduction suggests that radiation workers were more heavily exposed to asbestos and/or welding fumes than were other workers and that those exposures confounded the observed association between radiation and lung cancer. Analysis of mortality by time since first exposure to radiation revealed no pattern of progressive increase as latency increased. By contrast, odds ratios for asbestos/welding increased with latency. Data on cigarette smoking and socioeconomic status were not available. The results of this study do not preclude a possible association between radiation exposure at the Portsmouth Naval Shipyard and excess mortality from lung cancer. However, they provide no evidence in support of such a relation. PMID- 3337078 TI - Leisure time and occupational physical activity: risk of death from ischemic heart disease. AB - The relation of leisure time and occupational physical activity to the risk of death from ischemic heart disease was investigated in a cohort of 15,088 persons aged 30-59 years who had no history of cardiovascular disease or other condition which hindered physical activity. Two population samples were randomly chosen from eastern Finland. During a six-year follow-up, persons who were sedentary in leisure time (relative risk = 1.3, 95% confidence interval (CI) = 1.1-1.6) or at work (relative risk = 1.3, 95% CI = 1.1-1.6) had an excess risk of ischemic heart disease death when adjusted for age, health status, family history, and body mass index in multivariate logistic models. Adjustment for years of education, social network participation, cigarette consumption, serum cholesterol level, and blood pressure level weakened the residual association of low leisure time physical activity with the risk of ischemic heart disease death (relative risk = 1.2, 95% CI = 1.0-1.5), whereas the association for low occupational physical activity remained unchanged. The lack of leisure time physical activity and a sedentary occupation are associated with an increased risk of ischemic heart disease death, and the excess risk due to lack of leisure time physical activity is, in part, accounted for by other ischemic heart disease risk factors. PMID- 3337079 TI - On the ability of blood pressure effects to explain the relation between oral contraceptives and cardiovascular disease. PMID- 3337080 TI - The prevalence at birth of congenital malformations in communities near the Hanford site. AB - The authors examined the prevalence of congenital malformations among births in Benton and Franklin counties, in southeastern Washington State, from 1968 through 1980. The Hanford Site is in this area and serves as a major employer. In addition, various agriculturally and chemically related activities are in the area. Hospital and vital records were used to identify 454 malformation cases among 23,319 births; this yielded a malformation rate of 19.6 per 1,000 births, a rate similar to those reported in other studies. The rates of specific malformations ascertained during the first year of life were compared with combined rates from the states of Washington, Oregon, and Idaho from the Birth Defects Monitoring Program. Among defects that would be expected to be comparably ascertained, a statistically significant elevated rate of neural tube defects was observed (1.72 per 1,000 births vs. 0.99 per 1,000). Rates of cleft lip were significantly lower in Benton and Franklin counties than in the Birth Defects Monitoring Program (0.59 per 1,000 vs. 1.17 per 1,000). For congenital heart defects, pyloric stenosis, and Down syndrome, which are often not diagnosed in the newborn period, Birth Defects Monitoring Program data did not offer appropriate comparisons. The rates of these defects did not appear to be elevated in relation to rates found in other relevant populations. When rates of neural tube defects were compared with those in populations other than the Birth Defects Monitoring Program, the Benton and Franklin county rates were still considered to be elevated. The increased bicounty rate cannot be explained by employment of the parents at Hanford or by the impact of plant emissions on the local population. PMID- 3337081 TI - Radiation doses and cause-specific mortality among workers at a nuclear materials fabrication plant. AB - A historical cohort mortality study was conducted among 6,781 white male employees from a nuclear weapons materials fabrication plant for the years 1947 1979. Exposures of greatest concern are alpha and gamma radiation emanating primarily from insoluble uranium compounds. Among monitored workers, the mean cumulative alpha radiation dose to the lung was 8.21 rem, and the mean cumulative external whole body penetrating dose from gamma radiation was 0.96 rem. Relative to US white males, the cohort experienced mortality deficits from all causes combined, cardiovascular diseases, and from most site-specific cancers. Mortality excesses of lung and brain and central nervous system cancers were seen from comparisons with national and state rates. Dose-response trends were detected for lung cancer mortality with respect to cumulative alpha and gamma radiation, with the most pronounced trend occurring for gamma radiation among workers who received greater than or equal to 5 rem of alpha radiation. These trends diminished in magnitude when a 10-year latency assumption was applied. Under a zero-year latency assumption, the rate ratio for lung cancer mortality associated with joint exposure of greater than or equal to 5 versus less than 1 rem of both types of radiation is 4.60 (95% confidence limits (CL) 0.91, 23.35), while the corresponding result, assuming a 10-year latency, is 3.05 (95% CL 0.37, 24.83). While these rate ratios, which are based on three and one death, respectively, lack statistical precision, the observed dose-response trends indicate potential carcinogenic effects to the lung of relatively low-dose radiation. There are no dose-response trends for mortality from brain and central nervous system cancers. PMID- 3337082 TI - The reliability of passive smoking histories reported in a case-control study of lung cancer. AB - A test-retest design has been used to examine the reliability of passive smoking histories reported in personal interviews. A total of 117 control subjects initially interviewed in a lung cancer case-control study conducted in metropolitan Toronto, Canada, between 1983 and 1984 were reinterviewed on average six months later. Responses to initial screening questions used to detect a person's exposure to passive smoke were more reliable for residential than for occupational exposure. Respondents also more reliably reported residential exposure to spouse's passive smoke than to the passive smoke of others at home. Quantitative measures of exposure to passive smoke, i.e., number and duration of exposure, were even less reliably reported. Nonsmoking respondents gave the most reliable information. The low reliability of self-reported duration of exposure to passive smoke is consistent with the inability of several studies to detect a significant dose-response relation with lung cancer risk when measures of dose that depend solely on duration are used. PMID- 3337083 TI - The effects of maternal smoking on fetal and infant mortality. AB - Although maternal cigarette smoking has been shown to reduce the birth weight of an infant, previous findings on the relation between smoking and fetal and infant mortality have been inconsistent. This study used the largest data base ever available (360,000 birth, 2,500 fetal death, and 3,800 infant death certificates for Missouri residents during 1979-1983) to assess the impact of smoking on fetal and infant mortality. Multiple logistic regression was used to estimate the joint effects of maternal smoking, age, parity, education, marital status, and race on total mortality (infant plus fetal deaths). Compared with nonsmoking women having their first birth, women who smoked less than one pack of cigarettes per day had a 25% greater risk of mortality, and those who smoked one or more packs per day had a 56% greater risk. Among women having their second or higher birth, smokers experienced 30% greater mortality than nonsmokers, but there was no difference by amount smoked. The prevalence of smoking in this population was 30%. It was estimated that if all pregnant women stopped smoking, the number of fetal and infant deaths would be reduced by approximately 10%. The higher rate of mortality among blacks compared with whites could not be attributed to differences in smoking or the other four maternal characteristics studied. In fact, the black white difference was greater among low-risk women (e.g., married multiparas aged 20 and over with high education) than among high-risk women (e.g., unmarried teenagers with low education). PMID- 3337084 TI - Vitamin supplement use, by demographic characteristics. AB - Detailed data on vitamin supplement use are presented for nine specific vitamins and minerals by a wide range of demographic and behavioral characteristics. Previously recorded but uncoded data from the first National Health and Nutrition Examination Survey (1971-1974) have been coded and analyzed, providing the only detailed vitamin use data in a representative sample large enough to examine joint distributions and multivariate analyses of numerous characteristics. Significantly fewer black persons than white persons consume vitamins regularly, and the difference is especially pronounced for specific vitamins: fourfold for vitamin E, sixfold for vitamin A, and 10-fold for vitamin C. Significant differences were also seen for age, sex, geographic region, education, poverty, type of alcoholic beverage consumed, and Quetelet index. Data are presented indicating that supplement use has not increased notably between the time of the survey and 1983, and thus the supplement use data are considered to be reasonably representative of current patterns of supplementation practice in the United States. PMID- 3337085 TI - Alcohol consumption, type A behavior, and demographic variables. Results from the Normative Aging Study. AB - This study describes the relations of patterns of alcohol consumption with Type A behavior, age, retirement, marital status, and socioeconomic status among male participants in the Veterans Administration Normative Aging Study. In April 1984, 1,663 men completed form N of the Jenkins Activity Survey; in September 1982, 1,556 of these men had responded to a mailed survey of drinking behaviors. When age, marital status, socioeconomic status, and retirement status were controlled for, Type A score was virtually unrelated to the probability of being a nondrinker, having three or more drinks per day, problems with drinking, and periodic heavier drinking. Three other measures from the Jenkins Activity Survey- speed and impatience, hard-driving and competitive, and involvement--also had little association with these drinking behaviors. Moderate drinking was found to be strongly associated with higher socioeconomic status and being married. Results suggest that socioeconomic status and possibly marital status, but not Type A behavior and retirement, may influence the relation of drinking with the development of coronary heart disease. PMID- 3337086 TI - Plasma uric acid level and its association with diabetes mellitus and some biologic parameters in a biracial population of Fiji. AB - Plasma uric acid was investigated in a population survey on diabetes and cardiovascular risk factors among Melanesians and Asian Indians in Fiji in 1980. Plasma uric acid levels were elevated in men and women with impaired glucose tolerance in both ethnic groups. The lowest plasma uric acid levels were found in diabetic patients, especially in diabetic men. Even though obesity was positively associated with plasma uric acid, it did not explain the high plasma uric acid level in persons with impaired glucose tolerance. Body mass index had a significant and independent impact on plasma uric acid levels both in nondiabetic and diabetic men and women. The strongest predictor of plasma uric acid in the multiple regression analysis in our study populations was plasma creatinine: it alone explained 9% of the variation in men and 2% in women; and 24% in Melanesians and 5% in Asian Indians. Our findings suggest a strong renal involvement in the balance of plasma uric acid and may also reflect certain dietary patterns, such as a high intake of protein, fats, and certain local vegetables. Although the prevalence of hyperuricemia was high, 27% in both Melanesian men and women, 22% in Asian Indian men, and 11% in Asian Indian women, clinical gout was uncommon. Many predictor variables and their interactions were analyzed along with the reasons for the high plasma uric acid levels in persons with impaired glucose tolerance and for the low plasma uric acid levels in diabetic patients. PMID- 3337087 TI - Efficacy of sequential annual vaccination with inactivated influenza virus vaccine. AB - Inactivated influenza virus vaccine efficacy after annual revaccination has been reported to be less than that after first vaccination in boarding school children. We prospectively examined the immunogenicity and efficacy of this vaccine in healthy 30- to 60-year-old volunteers in Houston, Texas, over two epidemic seasons (1983-1985) encompassing outbreaks due to influenza A (H3N2 and H1N1) and influenza B viruses. A placebo group that had never (or not in recent years) received inactivated influenza virus vaccine, a group that received the vaccine for the first time (first vac), and a group given two or more recent vaccinations (multivac) were evaluated in a double-blind fashion each year. Vaccination induced higher frequencies of rise in serum antibody titer to vaccine components in first vac than in multivac volunteers, but mean postvaccination titers were similar. Clinical and virologic evaluations of illnesses during both epidemics and of influenza infections diagnosed serologically over the epidemic seasons revealed no overall reduction in illness from that in the placebo group for either vaccine group; modest reductions in influenza infection-related illness that were significant only for the multivac group against A/H3N2-related illness (55%; p less than 0.04); reduction in moderate-to-severe lower respiratory and/or systemic illness due to influenza for multivac (73%, p less than 0.025) but not first vac (15%, p greater than 0.10) volunteers during the A/H3N2 epidemic; reduction in influenza virus shedding in the multivac (54%, p less than 0.05) but not the first vac (16%, p greater than 0.10) group when compared with the placebo group for both years; and overall 63-81% reductions in documented infections with each influenza virus for both vaccine groups with the exception of A/H1N1 for the first vac group (24%, p greater than 0.10) and type B for the multivac group (58%, p = 0.067). Vaccine efficacy was only modest in these studies, but in contrast to the earlier report in boarding school children, efficacy appeared to be somewhat greater after repeated annual vaccination than after first administration. PMID- 3337088 TI - Malnutrition and diarrhea. A longitudinal study among urban Mexican children. AB - To address the hypothesis that malnutrition is associated with an increased risk of diarrhea, the authors identified a cohort of 284 Mexican children less than two years of age in order to equally represent different degrees of nutritional status. Nutritional status, defined anthropometrically, was measured at baseline and every three months for a total follow-up period of one year. The occurrence of diarrhea was assessed by weekly home visits. Among the combinations of weight and length examined, weight for age was the strongest predictor of subsequent diarrhea during a three-month interval. Among normally nourished children, the incidence of diarrhea was 3.3 episodes per year; among those mildly malnourished, 3.7 episodes per year (relative risk (RR) = 1.1); and among the moderately malnourished, 6.0 episodes per year (RR = 1.8). Adjustment for demographic, seasonal, and socioeconomic variables only slightly reduced this association. Nutritional status was most strongly related to the occurrence of two or more episodes during a three-month follow-up interval, and this effect was most clearly seen among children with diarrhea in the preceding interval. In a multiple logistic analysis that included potentially confounding variables as well as an autoregressive term to account for the nonindependence of repeated observations, the relative risk of two or more episodes of diarrhea during an interval was 1.8 (95% confidence interval 1.1-2.9) for moderately malnourished children compared with those who were normally nourished or mildly malnourished. These data lend support to the hypothesis that malnutrition predisposes to the occurrence of diarrhea among young children. PMID- 3337090 TI - Hospital visitors as controls. PMID- 3337089 TI - Interval estimates for correlation coefficients corrected for within-person variation: implications for study design and hypothesis testing. AB - It is well known that random measurement error can attenuate the correlation coefficient between two variables. One possible solution to this problem is to estimate the correlation coefficient based on an average of a large number of replicates for each individual. As an alternative, several authors have proposed an unattenuated (or corrected) correlation coefficient which is an estimate of the true correlation between two variables after removing the effect of random measurement error. In this paper, the authors obtain an estimate of the standard error for the corrected correlation coefficient and an associated 100% x (1 alpha) confidence interval. The standard error takes into account the variability of the observed correlation coefficient as well as the estimated intraclass correlation coefficient between replicates for one or both variables. The standard error is useful in hypothesis testing for comparisons of correlation coefficients based on data with different degrees of random error. In addition, the standard error can be used to evaluate the relative efficiency of different study designs. Specifically, an investigator often has the option of obtaining either a few replicates on a large number of individuals, or many replicates on a small number of individuals. If one establishes the criterion of minimizing the standard error of the corrected coefficient while fixing the total number of measurements obtained, in almost all instances it is optimal to obtain no more than five replicates per individual. If the intraclass correlation is greater than or equal to 0.5, it is usually optimal to obtain no more than two replicates per individual. PMID- 3337091 TI - Evidence of a pitfall in control selection for a community-based environmental health survey. PMID- 3337092 TI - Testicular cancer in US Navy personnel. AB - Age-adjusted and age-specific incidence rates of testicular cancer in US Navy personnel did not differ significantly from those of the US population, and age adjusted incidence rates did not increase with length of service in the Navy. There was a group of three occupations, however, which involved duties similar to those of the civilian occupation of automobile mechanic, and which had a significantly elevated age-adjusted rate of testicular cancer compared with the US population and the total Navy population. These occupations were aviation support equipment technician, engineman, and construction mechanic. All involve maintenance of internal combustion engines and exposure to the attendant lubricants, solvents, paints, and exhausts. PMID- 3337093 TI - Re: "Epidemiology of fecal mutagenicity". PMID- 3337094 TI - Re: "Diet and lung cancer risk". PMID- 3337095 TI - National Kidney Foundation report on dialyzer reuse. AB - Numerous organizations have presented their views previously on the reprocessing of hemodialyzers. These were well summarized by Easterling (Easterling, RE: Regulations and Standards, in Deane, Wineman, Bemis [eds]: Guide to Reprocessing of Hemodialyzers. Martinus Nijhoff, 1986, pp 183-197). The publication of the Recommended Practice by the Association for the Advancement of Medical Instrumentation (AAMI) on the reprocessing of dialyzers, coupled with the announcement of the Federal Government to accept these as the basis for Regulations administered by HCFA (now published as "Standards for the Reuse of Hemodialyzer Filters and Other Dialysis Supplies," Federal Register, Oct. 2, 1987), prompted the President of The National Kidney Foundation, Dr Richard Glassock, to appoint a Task Force to formulate the Foundation's position on the above. The members of the Task Force were: Michael J. Fisher, Raymond Hakim, MD, Nathan W. Levin, MD, Chairperson, John M. Newmann, PhD, David A. Ogden, MD, and Vincent Pizziconi, PhD. After having reviewed the previous NKF report on the issue of dialyzer reuse (American Journal of Kidney Diseases 3:466, 1984), the Task Force resolved that the principles of patient consent to dialyzer reuse and right to refuse a reused dialyzer as presented in the report be reaffirmed. While accepting the AAMI Recommended Practice as the basis for its recommendations, the Task Force recognized that the concerns of some patients were not met by the document. In addition to a number of technical amendments that were proposed, the Task Force, acting in the interest of patients, felt that it was essential to add information concerning the potential advantages and disadvantages of reuse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337096 TI - Vancomycin dosing chart for use in patients with renal impairment. AB - A new vancomycin dosing chart for use in patients with impaired renal function is described. The chart has been adapted from a previously published nomogram, based on a linear relationship between vancomycin clearance and creatinine clearance. Doses are designed to achieve an average steady-state serum concentration of approximately 15 mg/L. Use of the chart necessitates first measuring or estimating the patient's body weight and creatinine clearance. The chart provides the advantages of generating an exact dose and dosing interval, as well as being somewhat easier to use than the original nomogram. Predicted average steady-state serum concentrations resulting from the dosing chart range from 12.1 to 18.2 mg/L, with a mean of 15.0 mg/L. PMID- 3337097 TI - The effect of red cell transfusion on hemodialysis-related hypotension. AB - Blood pressures of 25 stable end-stage renal disease patients with chronic anemia (mean hemoglobin 5.9 g/dL) who had received 2 units of packed red cells during hemodialysis were studied. Three treatments preceding and three following the transfusion dialysis were compared. Twenty-eight hypotensive episodes preceded and 12 followed transfusion (P = .02). Intravenous sodium chloride used for hypotension declined from a mean of 20.4 to 10.2 mEq per dialysis (P = .01). The rate of decline in mean arterial pressure during dialysis was significantly slower following transfusion (P less than .01). Mean postdialysis weight fell from 62.0 kg before transfusion to 61.5 kg following transfusion (P less than .001). Thus, red cell transfusion raises intradialytic pressure and reduces the frequency of intradialytic hypotension. PMID- 3337098 TI - Continuous arteriovenous hemodiafiltration: an aggressive approach to the management of acute renal failure. AB - Continuous arteriovenous hemodiafiltration (CAVHD) offers a modified therapeutic approach to the patient with acute renal failure. The system employs a hollow fiber dialyzer, whose perfusion is dependent on the patient's BP. Peritoneal dialysis solution is infused through the dialysate ports in a direction countercurrent to blood flow at a rate of 500 to 1,500 mL/h. Five complex patients with acute renal failure were treated with CAVHD for periods ranging from two to 40 days. Urea clearances approached 37 L/d, and in stable patients, the BUN was maintained at 40 to 60 mg/dL and serum creatinine 1.4 to 4.0 mg/dL. Ultrafiltration up to 1 L/h could be obtained without difficulty. CAVHD is a safe and technically simple procedure that is particularly suitable for hemodynamically unstable patients with ongoing needs for fluid removal. PMID- 3337099 TI - Renal complications of acquired immunodeficiency syndrome in children. AB - A low incidence of renal disease was noted in a retrospective analysis of pediatric patients with acquired immunodeficiency syndrome. Episodes of acute renal failure were attributable to dehydration or nephrotoxicity. One patient, however, had nephrosis with focal glomerular sclerosis. Focal sclerosis involving 10% to 20% of glomeruli was evident in autopsy tissue from three patients. PMID- 3337100 TI - Sporadic aluminum osteomalacia: identification of patients at risk. AB - Chronic dialysis patients at risk for aluminum osteomalacia in areas of low water aluminum content are not well identified. We, therefore, studied retrospectively a cohort of 59 patients who underwent bone biopsy at two hospital-based dialysis centers in Montreal (water aluminum content less than 10 micrograms/L). Overall, 25% of patients biopsied had aluminum-related osteomalacia defined by aluminum staining of more than 30% of the trabecular surface and low levels of bone formation as measured by tetracycline labeling. Multiple linear regression analysis showed high predialysis serum creatinine (P less than .05) and the amount of aluminum prescribed per month (P less than .05) as the most important determinants of aluminum staining. We conclude that aluminum-related osteomalacia can be a frequent disease entity in areas of low water-aluminum content. Our findings also suggest predialysis serum creatinine and the amount of aluminum prescribed per month are risk factors for the development of aluminum-related osteomalacia. Though the relationship between serum creatinine and aluminum staining of trabecular bone is unclear, serum creatinine is probably a marker for adequacy of dialysis in these patients. PMID- 3337101 TI - Reversal of aluminum-related bone disease after substituting calcium carbonate for aluminum hydroxide. AB - Aluminum-related osteodystrophy, a crippling disease in patients with renal failure, can develop from the long-term ingestion of aluminum hydroxide gels. We present a diabetic patient treated with continuous ambulatory peritoneal dialysis (CAPD) who developed markedly elevated plasma aluminum levels but no musculoskeletal symptoms. Bone biopsy revealed features of the aplastic form of aluminum-related disease with significant aluminum staining, decreased osteoblastic osteoid, and decreased bone formation by double tetracycline labeling, but no excess accumulation of unmineralized osteoid. Aluminum hydroxide gels were discontinued and the patient received calcium carbonate to control hyperphosphatemia; 9 months later, a bone biopsy showed marked improvement of the aluminum-related bone disease, and at 2 to 10 months, plasma aluminum had decreased from 208.7 +/- 10.3 (SE) to 55.7 +/- 3.9 micrograms/L. PMID- 3337102 TI - Congestive cardiomyopathy in patients on continuous ambulatory peritoneal dialysis. AB - We present a report of cardiac dilatation and symptomatic congestive heart failure in two patients receiving treatment with continuous ambulatory peritoneal dialysis (CAPD). Both patients had previous partial parathyroidectomies and persistent hypocalcemia prior to the development of a congestive cardiomyopathy. The hypocalcemia was unresponsive to treatment with activated vitamin D therapy; however, intravenous replenishment of the ionized serum calcium level was accompanied by improvement in cardiac functional parameters. In one of the two patients, chronic calcium repletion with high dialysate calcium was associated with significant improvement in cardiac symptoms and a decrease in left ventricular dilatation. These observations suggest that partial parathyroidectomy and associated hypocalcemia place patients on CAPD at increased risk of cardiac dysfunction. PMID- 3337103 TI - Electrolyte case vignette: a case of unusual organic acidosis. PMID- 3337106 TI - Classification of experimental data for genetic analysis in autoimmune disease. PMID- 3337105 TI - HLA and the probability of paternity. AB - In cases of disputed paternity, blood tests are often used to obtain an estimate of the probability that the accused male is the true father. The interpretation of the genetic data is usually based upon a statistic called the paternity index. This paper shows that the paternity index method cannot be applied to data from compound loci in the absence of information on linkage phase. Since phenotypic data from compound loci, such as HLA, MNSs, and Rh, are often useful in disputed paternity proceedings, they should be analyzed with available alternative statistics. PMID- 3337107 TI - Evidence that autoimmunity in man is a Mendelian dominant trait. PMID- 3337104 TI - Simultaneous effects of the apolipoprotein E polymorphism on apolipoprotein E, apolipoprotein B, and cholesterol metabolism. AB - Human apolipoprotein (apo) E is polymorphic. We have investigated the effect of the apo-E polymorphism on quantitative plasma levels of apo E, apo B, and total cholesterol in a sample of 563 blood-bank donors from Marburg and Giessen, West Germany. The relative frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles are .063, .793, and .144, respectively. The average effects of the epsilon 2 allele are to raise apo-E levels by 0.95 mg/dl, lower apo B levels by 9.46 mg/dl, and lower total cholesterol levels by 14.2 mg/dl. The average effects of the epsilon 4 allele are to lower apo-E levels by 0.19 mg/dl, to raise apo-B levels by 4.92 mg/dl, and to raise total cholesterol levels by 7.09 mg/dl. The average effects of the epsilon 3 allele are near zero for all three phenotypes. The apo-E polymorphism accounts for 20% of the variability of plasma apo-E levels, 12% of the variability of plasma apo-B levels, and 4% of the variability of total plasma cholesterol levels. The inverse relationship between the genotype specific average apo-E levels and both the genotype-specific average apo-B and cholesterol levels is offset by a positive relationship between apo-E levels and both apo-B and cholesterol levels within an apo-E genotype. The apo-E polymorphism also has a direct effect on the correlation between apo-E and total cholesterol levels. The implication of these results on multivariate genetic analyses of these phenotypes is discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337108 TI - On the estimation of the proportion of sporadic cases in Duchenne muscular dystrophy. PMID- 3337109 TI - No evidence for genetic heterogeneity in cystic fibrosis. PMID- 3337110 TI - Undergraduate and postgraduate training programs for cytogenetic technologists. PMID- 3337111 TI - Genetics for nonbiology students: three suggestions. AB - This paper describes three techniques that have been found useful in the teaching of a human genetics course for students not oriented toward the biological sciences. These techniques are based on thirteen years of teaching such a course under an unusual academic calendar. PMID- 3337112 TI - Application of flow karyotyping in prenatal detection of chromosome aberrations. AB - This paper describes the application of bivariate flow karyotyping to (1) classification of chromosomes isolated from cultures of cells taken by amniocentesis and (2) detection of numerical and structural aberrations. Chromosomes were isolated from primary cultures 2-5 wk after amniocentesis, stained with Hoechst 33258 and chromomycin A3, and analyzed using dual beam flow cytometry. Information about chromosome DNA content and DNA base composition was derived from the locations of the peaks in the flow karyotypes, each peak being produced by one or more chromosome types with similar DNA content and DNA base composition. Information about the relative frequency of each chromosome type was determined on the basis of the relative volume of the peak for that chromosome type. Cytogenetic information determined on the basis of flow karyotypes was compared with that obtained by visual analysis following G-banding. Variability among the peak means and volumes in flow karyotypes was determined from analyses of 50 normal amniocyte cultures. Numerical aberrations involving chromosomes 21, 18, and Y were detected correctly in all of 28 analyses, including eight in a blind study. Structural aberrations involving chromosomes 1, 2, 3, 6, 9-12, 13, 14, 15, 21, and 22 were detected in all of seven cultures in a blind study. Flow karyotypes proved to be insensitive to small, normally occurring chromosome polymorphisms detected by banding analysis. In addition, a few samples were erroneously scored as having numerical aberrations. PMID- 3337113 TI - Patients with an inherited syndrome characterized by immunodeficiency, microcephaly, and chromosomal instability: genetic relationship to ataxia telangiectasia. AB - Fibroblast cultures from six unrelated patients having a familial type of immunodeficiency combined with microcephaly, developmental delay, and chromosomal instability were studied with respect to their response to ionizing radiation. The cells from five of them resembled those from individuals with ataxia telangiectasia (AT) in that they were two to three times more radiosensitive on the basis of clonogenic cell survival. In addition, after exposure to either X rays or bleomycin, they showed an inhibition of DNA replication that was less pronounced than that in normal cells and characteristic of AT fibroblasts. However, the patients are clinically very different from AT patients, not showing any signs of neurocutaneous symptoms. Genetic complementation studies in fused cells, with the radioresistant DNA synthesis used as a marker, showed that the patients' cells could complement representatives of all presently known AT complementation groups. Furthermore, they were shown to constitute a genetically heterogeneous group as well. It is concluded that these patients are similar to AT patients with respect to cytological parameters. The clinical differences between these patients and AT patients are a reflection of genetic heterogeneity. The data indicate that the patients suffer from a chromosome-instability syndrome that is distinct from AT. PMID- 3337114 TI - An epidemiologic approach to ecogenetics. AB - Although "ecogenetics" seeks to examine genetically mediated differences in susceptibility to environmental agents, researchers often examine the relation between genetic markers and disease without regard to environmental determinants. By using epidemiologic definitions of genotype-environment interaction, it can be shown that the relative risk of disease for the genetic marker is a function of the frequency of exposure to the environmental agent, the strength of interaction between the genotype and the agent, and the specificity of the environmental effect vis-a-vis the genotype. Using examples from the literature, we illustrate under six patterns of genotype-environment interaction that the relative risk associated with the marker can fluctuate markedly. However, with infrequent exposures, the relative risk is close to unity (implying no genetic effect) even in the face of strong genotype-environment interaction. Alternatively, elevated relative risks imply a frequent environmental exposure or a strong pattern of interaction. We suggest that genetic marker-disease associations be evaluated within the context of an epidemiologic study design that considers specific environmental determinants of risk. PMID- 3337115 TI - Chest pain: relationship of psychiatric illness to coronary arteriographic results. AB - Seventy-four patients with chest pain and no prior history of organic heart disease were interviewed with a structured psychiatric interview immediately after coronary arteriography. The majority of patients with both negative and positive coronary angiographies had undergone previous exercise tolerance tests, but the patients with angiographic coronary artery disease were significantly more likely to have had positive results on a treadmill test. Patients with chest pain and negative coronary arteriograms were significantly younger; more likely to be female; more apt to have a higher number of autonomic symptoms (tachycardia, dyspnea, dizziness, and paresthesias) associated with chest pain, and more likely to describe atypical chest pain. Patients with chest pain and normal coronary arteriographic results also had significantly higher psychologic scores on indices of anxiety and depression and were significantly more likely to meet criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, for panic disorder (43 percent versus 6.5 percent), major depression (36 percent versus 4 percent), and two or more phobias (36 percent versus 15 percent) than were patients with chest pain and a coronary arteriography study demonstrating coronary artery stenosis. PMID- 3337116 TI - IgA nephropathy, the most common glomerulonephritis worldwide. A neglected disease in the United States? AB - Although its prevalence and clinical importance in the United States are stated to be low, we believe IgA nephropathy occurs as commonly in this country as in Western Europe. Initial reports suggested the disease was perhaps restricted to France and synonymous with "benign recurrent hematuria," but longer follow-up has proven both conclusions incorrect. Obviously, major gaps persist in our understanding of the immunopathogenesis and the natural history. The latency of the American investigative response calls for more intensive clinical and laboratory studies of the most common primary glomerulonephritis worldwide. PMID- 3337117 TI - Do not go slowly into that dark night: mercy killing in Holland. PMID- 3337118 TI - Rupture of a pulmonary artery mycotic aneurysm associated with candidal endocarditis. AB - Candidal endocarditis can develop if candidemia occurs during Swan-Ganz catheterization. Candida endocarditis may persist for many months and is fatal unless the infected valve is resected. Herein is reported the first case of rupture of a mycotic pulmonary artery aneurysm caused by chronic candidal endocarditis. The endocarditis followed Swan-Ganz catheterization and aneurysm progressed despite appropriate medical and surgical therapy. PMID- 3337119 TI - Ethylene glycol intoxication: evaluation of kinetics and crystalluria. AB - Ethylene glycol and glycolate kinetics were studied in two cases of ethylene glycol intoxication with maximal ethylene glycol/glycolate concentrations of 40.9/26.8 and 56.4/22.4 mmol/liter, respectively. Both patients survived, but with prolonged renal failure, upon treatment with bicarbonate, ethanol, and hemodialysis. Glycolic acid was the major cause of the metabolic acidosis in both cases; lactate levels were only slightly elevated. Kinetic calculations showed that both ethylene glycol and glycolate were distributed in total body water with plasma half-lives of 8.4 and 7.0 hours, respectively. The half-life of ethylene glycol was increased more than 10-fold by ethanol treatment alone. Calcium oxalate monohydrate crystalluria was dominant in both cases, but in one was preceded by a short period with mainly dihydrate excretion; crystalluria was not present upon admission. Repetitive urine microscopy in search of needle- or envelope-shaped crystals should be performed when ethylene glycol intoxication is suspected. PMID- 3337120 TI - Recurrent hypercalcemia and elevated 1,25-dihydroxyvitamin D levels in Hodgkin's disease. AB - Hypercalcemia has been infrequently associated with Hodgkin's disease. When seen, most cases have been attributable to skeletal invasion by disease. Herein is described a 40-year-old man with a 15-year history of Hodgkin's disease. Each of four disease recurrences was heralded by hypercalcemia occurring in the absence of bone disease or elevation of parathyroid hormone levels. Marked elevations of 1,25-dihydroxyvitamin D levels were observed that paralleled his disease course and response to therapy. The repetitive association of hypercalcemia with an elevation of 1,25-dihydroxyvitamin D in this case provides further evidence of lymphoma-associated production of this vitamin. PMID- 3337121 TI - Endobronchial telangiectasias and hemoptysis in scleroderma. AB - Hemoptysis is considered a rare event in scleroderma and to date only two previous cases could be identified. The occurrence of hemoptysis with bleeding and friable telangiectasias is reported in a patient with rapidly progressing systemic sclerosis. This represents the first report of this association, although bleeding telangiectasias have been reported in other systems. A brief review of the relevant literature is included. PMID- 3337122 TI - What is safe sex? PMID- 3337123 TI - Osteosclerotic metastases with severe hypocalcemia, parathyroid hormone resistance, anemia, and cardiac failure. PMID- 3337124 TI - Emphysematous pyelonephritis. PMID- 3337125 TI - Dementia. PMID- 3337126 TI - Systemic lupus erythematosus and Klinefelter's syndrome. PMID- 3337128 TI - Divorce of mitral valve prolapse and neurocirculatory asthenia. PMID- 3337127 TI - Comparison of thrombolytic therapy for acute myocardial infarction in rural and urban settings. PMID- 3337129 TI - Diethylstilbestrol, clear cell adenocarcinoma, and striking discoveries in Norway. PMID- 3337130 TI - Treatment of non-toxic multinodular goiter with radioactive iodine. AB - Fourteen patients with large non-toxic multinodular goiters were treated with 20 to 100 mCi (740 to 3,700 MBq) of radioactive iodine (iodine-131). In seven, the goiter had recurred after a partial thyroidectomy and four of these had had two operations. Eight had symptoms of respiratory obstruction, two had dysphagia, and the others sought treatment for cosmetic reasons. After administration of iodine 131, there was a significant decrease in goiter size in 11 of the 14 patients, and all those with obstructive symptoms showed improvement. No significant local side effects occurred, but hypothyroidism and Graves' disease each occurred once during follow-up from one to 13 years. Radioactive iodine in doses of 20 to 100 mCi is an effective, safe therapeutic alternative in patients with large non toxic multinodular goiter, particularly when there is recurrence following surgery or when there are contraindications to surgery. PMID- 3337131 TI - Results of subtotal parathyroidectomy in hemodialysis patients. AB - In 61 hemodialysis patients undergoing subtotal parathyroidectomy, there was a good correlation between the preoperative serum immunoreactive parathyroid hormone value (iPTH) and the weight of parathyroid tissue removed surgically (p less than or equal to 0.001). Postoperatively, iPTH decreased rapidly from an initial mean (+/- SD) of 2,928 +/- 1,600 muleq/ml and remained at 365 +/- 296 muleq/ml at last follow-up of patients still undergoing hemodialysis (normal, less than 50 muleq/ml). Of six patients who had recurrent hyperparathyroidism (10 percent of total), three required a second subtotal parathyroidectomy. Aluminum related osteomalacia eventually developed in six patients with bone biopsy-proven hyperparathyroidism before parathyroidectomy. Nine patients with severe fracturing bone disease and hypercalcemia preoperatively but without clear evidence of hyperparathyroidism did not show a favorable response to subtotal parathyroidectomy (high mortality within 28 months, persistence of hypercalcemia, and symptomatic bone disease). Thus, subtotal parathyroidectomy can benefit patients with clearly established severe progressive hyperparathyroidism not responsive to medical therapy but is contraindicated in patients with low iPTH values and no bone biopsy evidence of severe hyperparathyroidism. PMID- 3337132 TI - Useful clinical criteria for the diagnosis of ventricular tachycardia. AB - Misdiagnosis occurs upon initial presentation to medical attention in a considerable number of patients referred for evaluation of wide QRS tachycardia. In order to improve diagnostic accuracy (ventricular versus supraventricular tachycardia), the answers to two key bedside questions were prospectively evaluated: (1) Had the patient experienced a prior myocardial infarction? (2) Did symptoms of tachyarrhythmia start only after the infarction? A patient presenting with a wide QRS tachycardia was considered to have ventricular tachycardia if he or she answered in the affirmative to both of these questions. Of 31 consecutive patients referred with electrocardiographically documented sustained wide QRS tachycardia that was reproduced in the electrophysiology laboratory, the diagnoses made when the patients first presented to medical attention were ventricular tachycardias in 17 patients and supraventricular tachycardias in 14 patients. Following electrophysiologic evaluation, 29 were diagnosed as having ventricular tachycardia and two as supraventricular tachycardia. If the diagnoses were made solely on the basis of responses to the bedside questions mentioned earlier, 28 of the 29 patients having a final diagnosis of ventricular tachycardia would have been correctly identified. It is concluded that the use of these two questions can be very helpful in improving the clinical diagnosis of ventricular tachycardia. PMID- 3337133 TI - Indolent epidemic of Pseudomonas cepacia bacteremia and pseudobacteremia in an intensive care unit traced to a contaminated blood gas analyzer. AB - An epidemic of Pseudomonas cepacia bacteremia and pseudobacteremia occurred in the medical intensive care unit at the Clinical Center of the National Institutes of Health. Sixteen patients in the intensive care unit became colonized or infected with this organism in a 21-month period; whereas P. cepacia had been isolated only 16 times in the preceding 90 months from the entire hospital. Further analysis demonstrated a significant association of the epidemic cases with bloodstream isolation of the organism (p less than 0.001, Fisher's exact test). Mortality associated with bacteremia caused by P. cepacia was 38 percent. Intensive investigation of the intensive care unit and its surrounding environment eventually demonstrated that a blood gas analyzer in a satellite laboratory adjacent to the intensive care unit was the reservoir for the outbreak. Replacement of the machine resulted in termination of the outbreak, P. cepacia continues to represent an environmental threat to hospitalized patients. PMID- 3337134 TI - Treatment of central nervous system toxoplasmosis with pyrimethamine/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome. Efficacy of long-term continuous therapy. AB - Thirty-five patients with the acquired immunodeficiency syndrome (AIDS) and central nervous system toxoplasmosis, seen over a 30-month period, were treated with the combination pyrimethamine/sulfadiazine. All patients had clinical and computed tomographic scan findings consistent with active neurotoxoplasmosis. Mean duration of total therapy was six months. During the first two months of therapy, four patients died of acute neurotoxoplasmosis and 31 showed improvement. Of the 24 patients evaluable for long-term therapy, 14 (58 percent) achieved complete resolution and 10 had late clinical (n = 7) and/or computed tomographic scan (n = 6) sequelae. Six patients experienced 10 relapses, which occurred within six weeks of treatment discontinuation in seven of 10. Reintroduction of the combination led to complete resolution of the relapse in eight cases. These clinical results were correlated with brain anatomic findings in the 15 autopsied cases. Side effects, noted in 25 of 35, were mainly hematologic toxicity (n = 21) and cutaneous rash (n = 12). However, the combination had to be definitively stopped in only two cases and sulfadiazine alone had to be withdrawn in eight other cases. These data suggest that pyrimethamine/sulfadiazine is highly efficacious in neurotoxoplasmosis and that life-long therapy is needed to prevent relapses in patients with AIDS. PMID- 3337135 TI - Effect of laboratory error on the identification of persons with hypercholesterolemia in an employee health service. AB - Cholesterol is a major risk factor for coronary heart disease. Of 117 employees seen consecutively in the Tennessee State Employee Health Service voluntary screening program, 86 (74%) had cholesterol levels above the reference range reported by a commercial clinical laboratory. This was three times greater than the calculated expected number of 29 (25%, 17 at moderate risk, 12 at high risk for coronary disease). Age and sex adjustment using Lipid Research Clinic guidelines reduced the number with elevated cholesterol to 55 (47%, 24 at moderate risk, 31 at high risk). Split sample cholesterol assays run independently by the commercial laboratory and a university laboratory showed excellent correlation (r = 0.99, commercial laboratory = 1.0 (university laboratory) + 10.8), but a systematic difference of 12.4 mg/dL (SD = 6.4 mg/dL, paired-t = 9.63, p less than 0.00001) between the two laboratories. Further adjustment for this difference reduced the number with elevated cholesterol to 41 (36%, 26 at moderate risk, 15 at high risk). This experience illustrates how small systematic laboratory errors in cholesterol determination can greatly exaggerate the number of persons reported to have clinically important cholesterol elevations. Clinical laboratories should report age and sex adjusted cholesterol reference ranges and provide clients periodic quality assurance reports that their measurements of cholesterol levels are accurate. PMID- 3337136 TI - Thyrotropin-induced hyperthyroidism: evidence for a common progenitor stem cell. AB - A 36-year-old woman with hyperthyroidism, elevated blood thyroid-stimulating hormone (TSH) and alpha-subunit levels, amenorrhea, hyperprolactinemia and no evidence of acromegaly, was found to have a pituitary adenoma containing TSH, alpha-subunit and growth hormone by immunohistochemistry. Preoperative testing revealed elevated TSH and alpha-subunit with no response to thyrotropin-releasing hormone (TRH) but a normal response in prolactin to TRH. Culture of the pituitary cells showed release of TSH, alpha-subunit and prolactin. In vitro, TRH failed to cause TSH discharge; however, it increased prolactin concentrations in the culture medium. Triiodothyronine, added to the pituitary cell culture, resulted in no inhibition of TSH and prolactin discharge. By electron microscopy, the adenoma cells showed features of thyrotrophs. However, some adenoma cells contained fibrous bodies characteristic of some growth hormone cell tumors and acidophil stem cell adenomas, suggesting that the adenoma originated in a common progenitor cell. PMID- 3337137 TI - Thrombocytopenia associated with repletion of iron in iron-deficiency anemia. AB - Two patients with iron deficiency experienced rapid decreases in their platelet levels following initiation of replacement therapy with oral ferrous sulfate or ferrous gluconate. The first patient, whose pretreatment platelet count was 168,000 per mm3, developed marked thrombocytopenia (platelet count, 21,000 per mm3) on the sixth day of iron repletion. The second patient's platelet level fell from 725,000 to 105,000 per mm3 on the tenth day of therapy. In both instances, platelet levels gradually returned to normal levels. The data suggest that the administration of oral iron resulted in an acute reduction in platelet production. The mechanism(s), prevalence, and clinical significance of thrombocytopenia following iron repletion in patients with iron deficiency anemia remain unknown. PMID- 3337138 TI - Relief of sleep apnea in acromegaly by bromocriptine. AB - A patient with longstanding acromegaly complicated by sleep apnea was treated with bromocriptine prior to surgery. In addition to a significant reduction of the plasma growth hormone concentration and measurable decrease in acral overgrowth, a dramatic improvement of the sleep apnea was observed. After three months of therapy, the amount of sleep time occupied by apneic episodes fell from 48 to 12%. The response indicates: (a) that the sequelae sleep apnea in acromegaly can be improved even when ablative therapy of the pituitary is impossible and (b) bromocriptine may prevent perioperative complications caused by clinically significant airway obstruction in patients with acromegaly. PMID- 3337139 TI - Two febrile drug addicts: treating self-destructive patients. PMID- 3337140 TI - Decide to manage your career. PMID- 3337142 TI - How do you define administrative support? PMID- 3337141 TI - How is autotransfusion done? PMID- 3337143 TI - The harmonics of nursing. PMID- 3337144 TI - Deciding factors. PMID- 3337146 TI - Positioning after a stroke. PMID- 3337145 TI - Nursing is... PMID- 3337147 TI - Hospitals that attract (and keep) nurses. PMID- 3337149 TI - The critical difference: pulmonary edema. PMID- 3337148 TI - The physiology of bed rest. PMID- 3337150 TI - Baggage from the past. PMID- 3337151 TI - Walking to better health. PMID- 3337152 TI - Taking a baby. PMID- 3337153 TI - Sibling visiting in the NICU. PMID- 3337154 TI - Overwhelming fatigue in advanced cancer. PMID- 3337155 TI - Woman battering. AB - Woman battering is a common phenomenon in our society. The number of women effected means that most obstetrician-gynecologists have patients in their practice who are victims. When the diagnosis is suspected, it is necessary to question the patient directly. Therapy involves the use of resources mostly outside of the office. Therefore, the physician assumes the role of (1) permission giving through mutual acknowledgement that the problem exists and is deserving of remedial action and (2) information giving by providing the patient sources of relief from the abuse. PMID- 3337156 TI - The role of cervical cerclage in the management of preterm premature rupture of the membranes. AB - The presence of a cervical cerclage at the time of preterm premature rupture of the membranes potentially complicates this already difficult management problem. An analysis of 44 patients presenting with preterm premature rupture of the membranes and cervical cerclage was conducted. Twelve patients were immediately delivered because of fetal distress, labor, or mature fetal pulmonary studies. Thirty-two patients entered an expectant management protocol. The cervical cerclage was removed on admission to the study. These patients were compared with 32 matched control subjects. There appears to be no difference in neonatal or maternal outcome between the study and control groups. The latency period from premature rupture of the membranes until delivery was not affected by the presence or removal of the cerclage. There was no difference in infectious complications. These data suggest that the presence of a cervical cerclage at the time of preterm premature rupture of the membranes does not increase the risk of delivery or infectious morbidity as long as the cerclage is removed early in the management protocol. PMID- 3337157 TI - Pregnancy after corticosteroid administration in premature ovarian failure (polyglandular endocrinopathy syndrome). AB - A patient with polyglandular failure syndrome first had documented ovarian failure at age 28 years. Fifteen years later after treatment for Addisonian crisis, she resumed menses, conceived, and was delivered of a normal infant. Patients with this syndrome should be identified because they are at risk for other endocrinopathies and because they may have a treatable form of ovarian failure. PMID- 3337158 TI - Umbilical amino acid concentrations in appropriate and small for gestational age infants: a biochemical difference present in utero. AB - Plasma amino acid concentrations were determined in 28 pregnant women and their infants at term. Samples were obtained from 17 appropriate for gestational age and eight small for gestational age infants at cesarean section, while three small for gestational age fetuses were studied in utero by transabdominal cord sampling by means of ultrasonic guidance. Small for gestational age fetuses have significantly lower concentrations of alpha-aminonitrogen, compared with those of appropriate for gestational age fetuses, in both the umbilical artery and vein. Most of the difference is accounted for by the branched chain amino acids valine, leucine, and isoleucine. In contrast, hydroxyproline concentration is significantly higher in both the umbilical artery and vein of small for gestational age fetuses. The sum of the branched chain amino acid concentrations in the umbilical vein is directly related to maternal arterial values in both appropriate for gestational age and small for gestational age fetuses. Maternal arterial concentrations were slightly lower in small for gestational age fetuses and the regression analysis of umbilical venous versus maternal arterial branched chain amino acid concentrations was significantly different for small for gestational age and appropriate for gestational age infants. Umbilical venoarterial concentration differences in normal fetuses are significantly positive for most essential amino acids and for total alpha-aminonitrogen. In contrast, these differences were significant only for four essential amino acids in small for gestational age infants, while the total alpha-aminonitrogen venoarterial difference was not significant. The data obtained by transabdominal cord sampling from relatively undisturbed fetuses were in agreement with the data obtained at cesarean section; this information suggests that these differences between small for gestational age and appropriate for gestational age infants reflected steady-state conditions. PMID- 3337159 TI - Successful treatment of hydrops fetalis caused by fetomaternal hemorrhage: a case report. AB - Nonimmune hydrops fetalis is a serious perinatal complication with diverse causes but few successful treatment modalities. The first reported case of hydrops fetalis caused by a massive fetomaternal hemorrhage treated successfully prenatally is presented. A modification of the standard intrauterine transfusion technique was used for therapy. Implications of future treatment are discussed. PMID- 3337160 TI - Fetal evaluation by percutaneous blood sampling. AB - Percutaneous umbilical blood sampling (cordocentesis) provides direct access to the fetal circulation in the second and third trimesters of pregnancy. Seventeen patients underwent this procedure between December 1985 and December 1986 for evaluation of a variety of clinical situations, including nonlethal fetal abnormalities detected by ultrasound, equivocal results of amniocentesis, nonimmune fetal hydrops, and isoimmune disorders. Our experience confirms the efficacy of the procedure and suggests that it may become an important tool for fetal assessment and therapy. PMID- 3337161 TI - Computed tomography in acute fatty liver of pregnancy. AB - A case of the diagnosis of acute fatty liver of pregnancy proved by biopsy is described. In this case computed tomography showed decreased attenuation over the liver, and this attenuation is compatible with fatty infiltration. Computed tomography may be useful in the differential diagnosis of jaundice in pregnancy. PMID- 3337162 TI - Fatal intrapartum pulmonary embolus during tocolysis. AB - Intrapartum pulmonary embolus, especially in association with hypercapnea, is an extremely dangerous situation requiring immediate detection and aggressive management. The predisposing factors of obesity and bed rest must be assessed, with strong consideration given to the use of prophylactic heparin. PMID- 3337163 TI - Absorbable synthetic mesh (polyglactin 910) for the formation of a pelvic "lid" after radical pelvic resection. AB - Isolation of the abdominal contents from the denuded, potentially infected pelvis after radical pelvic surgery has been advocated. Of the many materials evaluated, omentum is usually chosen. In six patients in whom omentum was unsuitable, we have substituted polyglactin 910 (Vicryl, Ethicon, Sommerville, New Jersey) mesh to form a pelvic "lid." In these patients, omentum was either densely adherent in the upper abdomen because of prior surgery or was removed as part of surgical treatment for recurrent cancer. Vicryl mesh formed a "lid" across the true pelvis. No gastrointestinal complications occurred in these patients. Four patients developed pelvic infections that resolved after surgical drainage and antibiotic therapy. No patients developed peritonitis above the pelvis. No chronic infections have been found in more than 12 to 48 months of follow-up. In this preliminary experience, Vicryl mesh appears to be useful for the formation of a pelvic "lid" after exenterative pelvic surgery when the omentum is unavailable. PMID- 3337164 TI - Antimicrobial activity of amniotic fluid against Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum. AB - Amniotic fluids obtained by amniocentesis at 16 weeks to term were examined for the presence of Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum. Of 140 fluids tested, none harbored chlamydiae, and only one harbored mycoplasma, M. hominis. A number of amniotic fluids were subsequently tested for their ability to inhibit the growth of these microorganisms. Amniotic fluids and chlamydial suspensions in a 2:1 ratio were incubated 30 to 90 minutes before their inoculation in McCoy cells. Procedures were followed for chlamydial isolation. Genital mycoplasmas were incubated with amniotic fluid samples for 24 or 48 hours at 35 degrees C. Growth in amniotic fluid specimens was compared with growth in pseudoamniotic fluid and broth controls. Fourteen amniotic fluid specimens collected from gestations of 16 to 40 weeks, were found to be inhibitory to the formation of inclusions of C. trachomatis in McCoy cells. Ten amniotic fluid specimens (16 to 39 weeks, gestation) demonstrated various degrees of inhibition against M. hominis, and three fluids were inhibitory to the growth of Ureaplasma. The inhibitor was heat and protease resistant and activity was proportional to concentration. The molecular weight of the inhibitor was probably greater than 10,000 daltons, and pH, although perhaps a contributing factor, was not the cause of the inhibition. PMID- 3337165 TI - Zinc status, pregnancy complications, and labor abnormalities. AB - Maternal plasma zinc levels, red blood cell levels, and serum alkaline phosphatase activity were used as indices of zinc status in 279 pregnant women at delivery and were compared with the incidence of complications during the antenatal period and major dysfunctional labor patterns. The median values for plasma zinc, red blood cell zinc, and alkaline phosphatase were used as cutoff points to subdivide the patient population into "low" and "high" groups. Low levels of maternal plasma zinc were associated with more complications in the antenatal or intrapartum periods than maternal levels of either alkaline phosphatase or red blood cell zinc. Plasma zinc levels less than the median value were more commonly associated with mild toxemia (p = 0.02), vaginitis (p = 0.01), and postdates (p = 0.01) in the antenatal period. During the intrapartum period, low plasma zinc levels were associated with a prolonged latent phase (p = 0.05), a protracted active phase (p = 0.04), labor greater than 20 hours (p = 0.03), second stage greater than 2.5 hours (p = 0.01), and cervical and vaginal lacerations (p = 0.02). Low levels of maternal alkaline phosphatase were strongly associated with a history of previous stillbirth (p = 0.0005). A low maternal red blood cell zinc level was not associated with complications during either period. Since a low plasma zinc level is a valid predictor of pregnancy complications and abnormal labor, the results suggest that plasma zinc screening, as part of the patient's antenatal workup should be evaluated. PMID- 3337166 TI - The use of intravenous pancuronium bromide to produce fetal paralysis during intravascular transfusion. AB - Intravascular fetal transfusion can be complicated by difficulty in maintaining vascular access because of fetal movements. Treatment by intramuscular pancuronium bromide has been proposed as a means of arresting fetal movements, although this treatment requires a separate puncture for injection. We report in this article our experience with intravenous fetal injection of pancuronium bromide to produce muscular paralysis during fetal transfusion. PMID- 3337167 TI - Agenesis of the pulmonary artery: an unusual cause of dyspnea in pregnancy. AB - A pregnancy complicated by dyspnea was associated with agenesis of the right pulmonary artery. The clinical characteristics of the agenesis of the pulmonary artery along with the differential diagnosis from pulmonary embolus are discussed. PMID- 3337168 TI - Acute oocyte loss in experimental autoimmune oophoritis as a possible model of premature ovarian failure. AB - A high incidence of autoimmune oophoritis can be induced in (C57BL/6Cr x A/J)F1 mice that were thymectomized at 3 days of age. The vaginal opening day was significantly delayed (thymectomized mice [n = 35], 38.1 +/- 5.8 days [mean +/- SD] versus sham thymectomized mice [n = 26], 34.0 +/- 5.2 days; p less than 0.02). Most of the thymectomized mice showed irregular estrous cycles during the first several weeks and then fell into continuous diestrus. Local infiltration of mononuclear and plasma cells inside and around growing follicles was a prominent feature in the early stage of oophoritis. This abnormal feature was first noticed at 24 days of age and progressed in the follicular units. Acute loss of oocytes, especially of growing follicles, with massive mononuclear cell infiltration rapidly progressed after puberty, and atrophic ovaries with complete destruction of both primordial and growing follicles were then seen for 1 to 2 months after puberty. In mice with oophoritis, circulating autoantibodies against, ooplasm, zona pellucida, or steroid-producing cells were constantly detected by immunohistochemical assay. Autoimmune thyroiditis and gastritis accompanied by specific circulating antibodies were also detected in mice thymectomized at 3 days of age. This experimental model may serve as a tool for studying premature ovarian failure in humans. PMID- 3337171 TI - Prolapsed vaginas treated by sacroplexy. PMID- 3337169 TI - Placental transport of riboflavin: differential rates of uptake at the maternal and fetal surfaces of the perfused human placenta. AB - The kinetics of riboflavin transfer across the perfused human placenta has been studied. With both circulations open, the transfer index (clearance of riboflavin: clearance of antipyrine) toward the fetus was 3.3 +/- 0.08 (+/- SD) versus 0.87 +/- 0.02 in the reverse direction (p less than 0.01). Galactoflavin reduced the materno-fetal transfer rate. The uptake of riboflavin and L-glucose after bolus injection into the maternal perfusate was 35% +/- 9.6% versus 3% +/- 16%, p = 0.005, which indicates an uptake rate in excess of diffusion. There was no significant difference in uptake at the fetal surface. With recirculation of either the maternal or fetal perfusate, the transplacental gradient that was established was lower at high concentrations of riboflavin, which indicates the saturability of this function. Riboflavin was concentrated in the intracellular space and partly metabolized to flavin mononucleotide and flavin adenine dinucleotide. An equilibrium was approximated when both perfusates were recirculated, with the concentration lowest in the maternal perfusate, highest in the placenta, and intermediate in the fetal perfusate. It is concluded that the major factor directing riboflavin toward the fetus is the difference in rates of uptake at the two surfaces of the placenta. PMID- 3337170 TI - The effect of human amniotic fluid on the isolated perfused rat heart. AB - To test the hypothesis that amniotic fluid directly affects cardiac function, isolated rat hearts were perfused with varying concentrations of centrifuged and filtered human amniotic fluid. The most consistent change seen was a dose dependent decrease in coronary flow rate. With 10% concentrations, a wide spectrum of changes was seen in both a positive and a negative direction for left ventricular pressure and change in pressure with respect to time, which were closely correlated with the degree of decrease in coronary flow rate. If amniotic fluid has a direct role in depressing cardiac function in amniotic fluid embolism, it may act by decreasing coronary flow rather than by directly suppressing myocardial activity. PMID- 3337173 TI - Fetal foot length as a predictor of fetal age. PMID- 3337172 TI - Is there a need for digital examination of patients with spontaneous rupture of membranes? PMID- 3337174 TI - Blood pressure during preeclampsia and matched control pregnancy. PMID- 3337176 TI - Iatrogenous remission of twin transfusion syndrome. PMID- 3337175 TI - Lead and cadmium concentrations in mother and fetus. PMID- 3337177 TI - Transcervical amnioinfusion of antibiotics: a basic study for managing premature rupture of membranes. AB - To determine the best method of preventing ascending infection in the management of premature rupture of membranes, antibiotics such as latamoxef sodium, cefoperazone sodium, and cefotaxime sodium were infused directly into the amniotic cavity in 64 patients undergoing induction of labor at term. A single infusion of 100 or 500 mg of each drug resulted in a concentration of 200 to 1000 micrograms/ml immediately after infusion, and the concentration remained above 10 micrograms/ml for about 24 hours without significant increase in fetal or maternal blood levels. Consequently, a daily single dose of 100 mg or more is probably effective prophylaxis in cases of premature rupture of membranes. When intrauterine infection is suspected, the dose can be increased to 500 mg or more, and transplacental administration may be added to achieve a higher concentration in fetal blood. The present study simulates well premature rupture of membranes, and an amnioinfusion of antibiotics will be reliable and effective in managing premature rupture of membranes. PMID- 3337178 TI - Symptoms associated with vaginal colonization with yeast. AB - We correlated vulvovaginal symptoms with vaginal cultures for yeast in healthy female college students. Yeasts were isolated from 42 (29.2%) of 144 women. Only four (22%) of 18 women with positive fungal cultures had fungal elements visualized microscopically in vaginal material suspended in 10% potassium hydroxide (potassium hydroxide wet preparations). Symptoms, mainly vulvovaginal itching and irritation, were reported by 28 (67%) of 42 women whose cultures contained yeast and by 22 (22%) of 102 women who were not colonized by yeast (p less than 0.01). We conclude that vaginal colonization by yeasts is commonly associated with vulvovaginal symptoms, often in the absence of positive potassium hydroxide wet preparation results. These data suggest that vaginal specimens from women who have vulvovaginal symptoms and negative potassium hydroxide wet preparation results should be cultured for fungi before the diagnosis of fungal vulvovaginitis is excluded. PMID- 3337179 TI - The influence of gestational age and preeclampsia on the presence and magnitude of serum endogenous digoxin-like immunoreactive substance(s). AB - Digoxin-like immunoreactive substance(s) has been measured in serum during pregnancy. Because of its presence in pregnancy, investigators have suggested that digoxin-like immunoreactive substance may play an etiologic role in the development of preeclampsia. The objectives of this study were to evaluate the relationship between maternal digoxin-like immunoreactive substance and gestational age and compare digoxin-like immunoreactive substance concentrations in patients with and without preeclampsia who were in the third trimester. Two hundred twenty patients were studied during either the first (n = 53), second (n = 56), or third (n = 111) trimester of pregnancy. Digoxin-like immunoreactive substance was undetectable in the serum of patients during the first trimester; however, 11% of second-trimester and 96% of third-trimester patients had measurable levels of serum digoxin-like immunoreactive substance (p less than 0.05). The mean +/- SEM concentration of digoxin-like immunoreactive substance in serum in third-trimester patients was 0.29 +/- 0.01 ng/ml (range 0 to 0.58 ng/ml). Gestational age at delivery was significantly lower in patients with preeclampsia than in those without preeclampsia (36.3 +/- 0.6 versus 38.8 +/- 0.4 weeks; p less than 0.001). In addition, there was no statistical difference in mean +/- SEM concentration of digoxin-like immunoreactive substance between 27 patients without preeclampsia (0.32 +/- 0.02 ng/ml) and 27 patients with preeclampsia (0.30 +/- 0.02 ng/ml; p = 0.47) matched for gestational age. We conclude that (1) digoxin-like immunoreactive substance appearance and increasing serum concentration during pregnancy are correlated with increasing gestational age and (2) there is no difference in digoxin-like immunoreactive substance values between patients with and without preeclampsia, which may exclude digoxin like immunoreactive substance as a predictor of preeclampsia. PMID- 3337180 TI - Ultrasonic imaging of normal fetal response to external vibratory acoustic stimulation. AB - Fetal facial reactions and response decrement patterns to external noise stimulation were studied to characterize normal fetal neurobehavior in the third trimester. Response decrement, or habituation, is thought to reflect higher central nervous system function. Two hundred women with uncomplicated pregnancies, who were subsequently delivered of healthy infants at term, were studied between 26 and 41 weeks' gestation. After ultrasound views of the fetal face were obtained, a vibratory acoustic stimulus was applied repetitively to the maternal abdomen near the fetal head. Response decrement was defined as cessation of all components of the facial reaction, except eye blinking, over two sequential stimuli. Three response patterns were scored: (1) no startle, (2) startle without response decrement, and (3) response decrement by 12 stimuli. Whereas only 53% of fetuses between 26 and 27 weeks displayed startle reaction, all fetuses displayed startle responses by 28 weeks. As gestational age advances, an increasing number of fetuses exhibit response decrement, from no decrement at 26 to 27 weeks to 100% decrement at 40 to 41 weeks. A maturation of neurobehavioral response patterns takes place in normal third-trimester pregnancies. Response decrement testing may be a useful tool for in utero neurologic evaluation. PMID- 3337181 TI - Effect of sperm antibodies on pregnancy outcome in a subfertile population. AB - The relationship between sperm antibodies, conception, and miscarriage was examined in 109 infertile couples. Antibodies present on the surface of husbands' ejaculated sperm and antibodies in husbands' or wives' sera that reacted with a purified population of the husbands' motile spermatozoa were detected by an enzyme-linked immunosorbent assay. During an 18-month period, conception occurred in 33 (30.3%) of the couples; 16 (14.7%) women subsequently suffered a spontaneous miscarriage during the first trimester, whereas 17 (15.6%) women maintained their pregnancies past this time period. Antisperm antibodies were present in sera from only two of 17 (11.8%) women with successful pregnancies, whereas seven of 16 (43.8%) women who miscarried and 29 of 76 (38.2%) who did not conceive had these antibodies in their sera. IgG (22.4%) and IgM (21.1%) antisperm antibodies predominated in sera of women who did not conceive, whereas IgA (37.5%) and IgG (37.5%) antibodies were most prevalent in sera of women with miscarriages. In men, the presence of antisperm antibodies in sera was unrelated to fertility. However, there was a correlation between sperm surface antibodies and an inability to conceive. IgG was identified on ejaculated spermatozoa from eight of 76 (10.5%) men whose wives failed to conceive and in none of 33 men whose wives conceived. Similarly, IgA was present on spermatozoa from 16 (21.1%) infertile and two (6.1%) fertile men. Thus antisperm antibodies in female sera and on ejaculated spermatozoa were associated with a failure to conceive and first-trimester miscarriage. PMID- 3337182 TI - Fetal acoustic stimulation in early labor in patients screened with the admission test. AB - Fetal heart rate reactions to the fetal acoustic stimulation test were investigated in 952 women in early labor. All had cephalic presentations (greater than 33 weeks of gestation) and were screened with a 15-minute fetal heart rate recording (admission test) before the sound stimulation was applied. Three different types of responses were observed: type I, an accelerative response; type II, a biphasic response with acceleration(s) followed by a deceleration; type III, no response or a prolonged deceleration (greater than 60 beats/min and greater than 60 seconds). A type I response was recorded in 98.0% of the women after a reactive admission test result, in 90.2% after an equivocal admission test result, and in 42.9% after an ominous admission test result. Fetal distress in labor occurred in these three groups in 2.0%, 22.2%, and 35.7% of cases, respectively. The risk for fetal distress was high after an ominous admission test and a type III response on the fetal acoustic stimulation test (75.0%). The fetal acoustic stimulation test might be of value in labor and give additional information about fetal well-being in patients previously screened by the admission test. Testing time can be shortened after an equivocal admission test. PMID- 3337183 TI - Fetal heart rate and fetal activity patterns after vibratory acoustic stimulation at thirty to thirty-two weeks' gestational age. AB - Twenty pregnant women between 30 and 32 weeks' gestational age were studied to examine the effects of a 5-second external vibratory acoustic stimulus on the fetal heart rate, fetal heart rate variability, and fetal activity patterns. There was an immediate significant increase in the basal fetal heart rate for 10 minutes compared with controls. There was also a significant increase in the mean duration of fetal heart rate accelerations without any change in the number of fetal heart rate accelerations. There were no changes in long-term fetal heart rate variability, fetal breathing, and gross fetal body movements. PMID- 3337184 TI - Maternal age and incidence of low birth weight at term: a population study. AB - A total of 184,567 singleton live births with gestational ages of 40 weeks were examined from the 1980-1984 Illinois birth certificate data to determine the independent effect of maternal age on the incidence of low birth weight at term. The incidence is highest in mothers less than 17 years of age (3.2%) and gradually declines with advancing maternal age to reach 1.3% in women aged 25 to 34 years. It increases to 1.7% for those greater than 35 years of age. To separate out the independent effect of maternal age on the incidence of low birth weight infants at term, the presence of other maternal factors, such as race, education, parity, marital status, and prenatal care, were adjusted by use of a series of multiple logistic regression analyses. All of these analyses consistently demonstrated that the adjusted risk for low birth weight at term is the lowest in teenagers and increases with advancing maternal age. These results indicate that the high incidence of this factor in young mothers apparently reflects their poor sociodemographic and prenatal care status. Advancing maternal age is associated with a decreased potential for fetal growth, possibly reflecting biologic aging of maternal tissues and systems or the cumulative effects of disease. PMID- 3337185 TI - The cerebral palsies in Western Australia: trends, 1968 to 1981. AB - Data were analyzed from all cases of cerebral palsy in a population-based register in Western Australia. The number of cases of cerebral palsy diagnosed by age 5 years varied little among cohorts of infants born between 1960 and 1982. Trends toward more intensive perinatal care, increasing frequency of cesarean section, and the increased use of electronic fetal monitoring to detect fetal distress were associated with decreases in perinatal mortality but not in cerebral palsy. The increase in survival of low birth weight infants has resulted in an increased number of children with cerebral palsy, but this has had a minimal impact on total cerebral palsy rates. These descriptive trends raise doubts about the relationship between cerebral palsy and perinatal events, the effects of obstetric and neonatal interventions in reducing cerebral palsy, and the use of cerebral palsy data as an index of perinatal care practices. PMID- 3337187 TI - Limbal- vs fornix-based conjunctival trabeculectomy flaps. PMID- 3337186 TI - A reassessment of infantile esotropia. XLIV Edward Jackson memorial lecture. AB - Essential infantile esotropia is an early acquired, not a congenital, condition, although congenital factors may favor its development between the ages of 3 and 6 months. It must be distinguished from other forms of esotropia with an onset between birth and the first six months of life. The cause of essential infantile esotropia remains unknown, but advances in our knowledge can be expected from the rapidly emerging discipline of infant psychophysics. In analyzing treatment results, a clear distinction must be made between normal, subnormal, and anomalous forms of binocular cooperation. While complete restoration of normal binocular function is rarely, if ever, achieved, anomalous binocular cooperation has many functional advantages over suppression or diplopia and should not be disturbed by overzealous treatment. Subnormal binocular vision is considered to be an optimal, microtropia a desirable, and a residual small angle heterotropia an acceptable end stage of surgical therapy. In a study of 358 surgically treated patients with a documented onset of essential infantile esotropia before age 6 months, subnormal binocular vision was present in 71 (20%), a microtropia in 25 (7%), and a small angle esotropia or exotropia in 140 (39%) of the patients. Surgical alignment before completion of the second year of life improved the chances for an optimal treatment result.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337188 TI - Clinical evaluation of the Oculab Tono-Pen. PMID- 3337189 TI - Nd:YAG laser photodisruption of the lens nucleus before phacoemulsification. PMID- 3337190 TI - Vitreous surgery for hemorrhagic and fibrous complications of age-related macular degeneration. AB - We applied vitreous surgical techniques in the treatment of hemorrhagic and fibrous complications of choroidal neovascular membranes by removing subretinal scars or hemorrhage, or both, in four patients. The surgical goals were achieved in all patients. Visual acuity improved in three patients. The major complication was recurrent detachment associated with large retinotomies. PMID- 3337191 TI - Prostaglandin F2 alpha-1-isopropylester lowers intraocular pressure without decreasing aqueous humor flow. AB - Using fluorophotometry, we performed a randomized, dose-response study of the effects of a prostaglandin derivative on aqueous humor flow. Prostaglandin F2 alpha 1-isopropylester, 0.224 micrograms, 0.448 micrograms, and 1.120 micrograms, in saline with polysorbate 80 was instilled into one eye of 20 subjects in three separate dose studies. Polysorbate 80 in saline was instilled in the fellow eye as a control. The drug had no measurable effect on aqueous humor flow or corneal endothelial permeability. Intraocular pressure measured eight hours after administration of the highest dose, 1.120 micrograms, was 20% lower in the treated eye as compared to the fellow eye (P less than .001). PMID- 3337192 TI - Response of blood flow to warm and cold in normal and low-tension glaucoma patients. AB - We measured blood flow in the finger in 38 control subjects with normal ocular findings without migraine, 13 control subjects with normal ocular findings with classic migraine, 17 patients with low-tension glaucoma with classic migraine, and 29 patients with low-tension glaucoma without migraine. Three blood flow measurements were recorded: one at baseline, one after immersion in warm water (40 C), and one after ten seconds' exposure to cold water (4 C). The mean baseline flow and the mean flow after exposure to cold was lower in patients with low-tension glaucoma (P = .013 and P less than .001, respectively). PMID- 3337193 TI - Cosegregation of X-linked retinitis pigmentosa and hemophilia A. AB - We examined a family pedigree in which retinitis pigmentosa and hemophilia A were inherited in an X-linked manner. Six female carriers were identified by electroretinography. Results of ophthalmoscopic examination were normal in two women, while four displayed marked variability in phenotypic expression. Six of seven males identified with retinitis pigmentosa had hemophilia A. One asymptomatic boy had a markedly abnormal electroretinogram despite normal ophthalmoscopic examination. Pedigree analysis showed a high recombination rate, which would be expected as these two genes are known to be at opposite arms of the X chromosome. PMID- 3337194 TI - The surgical treatment of blepharoptosis in oculomotor nerve palsy. AB - We reviewed retrospectively 170 cases of congenital and acquired oculomotor nerve palsy to determine the effectiveness of surgery in the treatment of blepharoptosis in oculomotor nerve palsy. Twenty patients had had surgical repair of the blepharoptosis. Patients with congenital oculomotor palsy were more often selected for blepharoptosis surgery than patients with acquired blepharoptosis because of the absence of diplopia caused by suppression in congenital cases. There was complete recovery in 72 of 109 patients (66%) with acquired oculomotor palsy. Results were judged with regard to functional improvements and cosmetic improvement. Primary functional disability was relieved by lifting the eyelid above the pupil in ten of 12 patients (83%). Primary cosmetic disability was relieved in six of six patients. Corneal complications occurred in six of 20 patients (30%) who were treated surgically. PMID- 3337196 TI - Bilateral keratitis as a manifestation of Lyme disease. AB - An 11-year-old girl developed bilateral keratitis, which we believe was a manifestation of Lyme disease. She had had several attacks of Lyme arthritis and was twice treated with parenteral penicillin. The keratitis developed five years after the initial episode of Lyme arthritis at a time when there were no other manifestations of Lyme disease. It cleared completely in both eyes after topical corticosteroid therapy. PMID- 3337195 TI - Linear subcutaneous fat atrophy after corticosteroid injection of periocular hemangiomas. AB - Two children developed evidence of subcutaneous fat atrophy after corticosteroid injection of periocular hemangiomas. The atrophy appeared at the site of injection and followed the expected course of lymphatic channels to the vicinity of regional lymph nodes. PMID- 3337197 TI - Respiratory arrest after two retrobulbar injections. PMID- 3337199 TI - Ocular examination before initiation of lovastatin (Mevacor) therapy. PMID- 3337198 TI - Acute psychosis associated with topical cyclopentolate hydrochloride. PMID- 3337200 TI - Familial keratoconus. PMID- 3337202 TI - Scintillating scotoma after retinal detachment surgery. PMID- 3337201 TI - Horner's syndrome associated with carotid artery atherosclerosis. PMID- 3337203 TI - Solar retinopathy in persons on religious pilgrimage. PMID- 3337204 TI - Dye yellow photocoagulation of retinal arterial macroaneurysms. PMID- 3337205 TI - Surgical treatment of acute glaucomatocyclitic crisis in a patient with primary open-angle glaucoma. PMID- 3337206 TI - Pattern of fluid accumulation in NO2-induced pulmonary edema in dogs. A morphometric study. AB - To ascertain whether the pattern of fluid accumulation could be altered by an agent introduced through the airways, the authors studied the physiology and morphology of 11 dogs exposed to 150-494 ppm.hr NO2 and compared them with 3 new and 5 previously reported control dogs. NO2 caused a partly reversible decrease in systemic arterial pressure and cardiac output, a fall in arterial PO2, and rapid shallow breathing, while pulmonary arterial and wedge pressures remained normal. Post mortem, lower (LL) and middle (ML) lobes were frozen, sections fixed for light microscopy by freeze-substitution, and wet weight/dry weight (W/D) ratios were measured. Alveolar edema was graded, and the distribution of interstitial edema around arteries and veins and within bronchovascular bundles was studied with morphometry: edema ratios (ER) were calculated as area of interstitium/area of vessel or airway. We found that NO2 produced an exposure dependent increase in lung water (r = 0.73), and that both LL and ML had similar W/D ratios (7.77 and 8.39, respectively) and percent alveolar edema (30% and 34%). Morphometry of interstitial edema showed that the ER for vessels and airways of edematous LL were essentially similar to controls, while those of the ML were markedly increased. It is concluded that NO2 produces exposure-related lung edema and preferential alveolar flooding with probable secondary interstitial accumulation. The discrepancies in interstitial edema between middle and lower lobes may be due to differences in lung volume or in ventilation. PMID- 3337207 TI - Inflammatory reaction in experimental hepatic amebiasis. An ultrastructural study. AB - One of the hallmarks of tissue necrosis produced by the human protozoan parasite Entamoeba histolytica, the causative agent of human amebiasis, appeared to be the lack of inflammatory reaction to the invading trophozoites. Recent evidence suggests, however, that inflammatory cells do appear during early stages of amebic destructive lesions and that they contribute to the establishment of foci of tissue necrosis in intestinal and liver lesions. The present analysis of the fine-structural changes that take place during early stages of amebic liver abscesses induced in hamsters after the intraportal inoculation of axenic amebas has shown that large numbers of polymorphonuclear leukocytes (PMNs) are recruited around invading amebas. These leukocytes lyse as a consequence of contact mediated damage induced by the trophozoites. Amebas were also capable of ingesting apparently intact PMNs. Macrophages and eosinophils were also recruited at the foci of inflammation. At all times examined, trophozoites of Entamoeba histolytica survived in spite of being in close contact with PMNs or degranulating eosinophils. The ultrastructural observations have also shown the lack of direct contact between amebas and liver parenchymal cells during the initial stages of the focal liver necrosis induced by the parasite, therefore supporting the view that hepatic damage may be effected indirectly through lysis of inflammatory cells. The results also provide a basis for the understanding of the induction of experimental protective immunity against invasive amebiasis, a process which seems to be mostly dependent on cellular mechanisms. PMID- 3337208 TI - Capillary structure in elastase-induced emphysema. AB - The essential component of pulmonary emphysema is destruction of alveoli. Because capillaries make up much of the alveolar wall, it has been a long-held opinion that capillary loss in this disease parallels the loss of other elements of the alveolar septum. Yet the nature of the damage to capillaries and the occurrence of microvascular remodeling are unknown. Scanning electron microscopy of vascular casts of lungs from rats given intratracheal elastase were studied for identifying capillary changes in this type of experimental emphysema. The pressure-volume curves showed a clear distinction between the elastase and saline control animals, and light microscopy showed alveolar enlargement consistent with mild emphysema. The casts of capillaries in the elastase lungs appeared to have larger alveolar baskets, and capillaries ended abruptly near areas of focally destroyed lung. The elastase animals had more nonconnecting capillary segments on the pleural surface where the emphysema was worse and folds in the capillaries were more pronounced, suggesting weakened alveolar walls. The capillary density was decreased on the pleural surface, although this decrease could have resulted from hyperinflation. No difference in capillary diameters or branching frequency occurred. It appears that in this model of emphysema, decreased elastic recoil occurs before diffuse loss of capillaries. PMID- 3337210 TI - Induction of arthritis in C57B1/6 mice by chlamydial antigen. Effect of prior immunization or infection. AB - Antigen from a Chlamydia trachomatis biovar, mouse pneumonitis agent (MoPn), was used to produce an inflammatory arthritis by inoculation in the knee joints of C57B1/6 mice. The production of arthritis was strongly dependent on prior sensitization to chlamydiae by subcutaneous immunization in either sex or genital infection in females. In unimmunized animals quantitatively less inflammation, fibrin exudation, and pannus formation developed than in immunized counterparts. In neither uninjected nor McCoy or HeLa Cell antigen-treated joints did arthritis develop. The arthritis produced was more pronounced at 7 than at 2 days after intraarticular challenge and showed minimal residual changes at 21 days. Residual changes included subsynovial hyperplasia. In genitally infected female mice less severe arthropathy developed than in subcutaneously immunized female mice after intraarticular challenge with formalin-inactivated chlamydial antigen. However, in infected mice challenged with chlamydiae inactivated by ultraviolet irradiation a severe arthritis with destructive pannus developed, suggesting alteration of antigenicity by formalin inactivation. The strong association of the arthritis with the presence of chlamydial antibody suggests its use as a model of human Reiter's disease in which prior sensitization to Chlamydia is an important factor. PMID- 3337209 TI - Radiation-induced lymphoblastic lymphomas/leukemias and sarcomas of mice express conserved, immunogenic 44-kilodalton oncofetal antigen. AB - X-ray-induced, lymphoblastic, T-cell lymphoma/leukemias from irradiated RF mice were observed to uniformly expressed a 44-kd oncofetal antigen (OFA). The OFA polypeptide was detected by flow cytometry, affinity column SDS-PAGE analysis, and immunoblotting with monoclonal antibody (MAb) 115 prepared against syngeneic mouse fetus. X-ray and ultraviolet (UV) induced murine fibrosarcoma cell lines, used as classic models in radiation biology, were also found to express the OFA, which suggested that the 44-kd OFA was a general transformation marker of tumors. Adult mouse thymocytes and other adult tissues expressed no OFA. The 44-kd polypeptide was located at the surface membrane of the tumors examined. In contrast to other reports, lymphoblastic lymphoma cell lines expressed the OFA as a cross-protective, rather than an individually-specific, tumor-associated transplantation antigen. Pronase treatment removed OFA from the surface of living lymphoma cells, whereas collagenase, neuraminidase, and hyaluronidase did not. The OFA was rapidly reexpressed upon culture of the pronase-treated cells. Taken together, these results suggest that the 44-kd OFA polypeptide described here may provide a useful cell surface marker for future radiation carcinogenesis studies. MAb 115 is a promising reagent for detecting tumor-associated 44-kd OFA, for assessing immunoregulatory perturbations to the OFA caused by radiation damage and for investigating the immunopathology of OFA-associated radiation damage. PMID- 3337211 TI - Proliferative and secretory activity in human breast during natural and artificial menstrual cycles. AB - Events of cell proliferation have been assessed by thymidine labeling index (TLI) in morphologically normal breast lobules from women of reproductive age. TLI is higher during the second half of the menstrual cycle both in women with natural menstrual cycles and in those with artificial cycles due to oral contraceptive (OC) use. TLI varies between 0.04% and 5.7% and declines with increasing age. There is no difference in mean TLI between OC users and nonusers if correction is made for the difference in age distribution between these two groups. Immunohistochemical detection of immunoglobulin A (IgA), secretory component (SC), and alpha-lactalbumin shows more frequent positive staining during artificial than natural menstrual cycles, and positive staining tends to be associated with higher TLI values. No significant variation in staining with cycle phase is detected in natural or artificial cycles. These results show that breast tissue does not resemble endometrium in the relationships that exist between proliferation, secretion, and menstrual cycle phase. PMID- 3337212 TI - Light- and electron-microscopic analysis of the kidney in newborn rats exposed to gentamicin in utero. AB - Kidneys of newborn rats, whose mothers were given 75 mg/kg of gentamicin daily from the tenth day of gestation to its term, were examined by light and electron microscopy, as were kidneys of control rats whose mothers were given saline during the same period. In the gentamicin-treated group, the numbers of differentiated glomeruli and of S-shaped bodies counted in a median cross-section of the kidney were reduced, compared with those in the control group, but the glomerular volume was the same. In newborn rats issued from gentamicin-treated mothers, the proximal tubular lumen of the mature nephron lying in the deepest cortex was dilated, and their proximal tubular cells exhibited extensive damage, resembling that described in tubular cells of adult rats exposed to gentamicin. The subcapsular nephrogenic zone exhibited focal alterations of cytoplasmic organelle membranes, as well as nuclear lesions of several types, in cells of the nephron anlagen of the undifferentiated metanephric blastema, which were otherwise of normal appearance. PMID- 3337214 TI - Calcium diffusion through perineurium of frog sciatic nerve. AB - Calcium and sucrose permeabilities (PCa or Psucrose) were calculated from the fluxes of 45Ca and [3H]sucrose across perfused everted and normal configurations of the perineurial cylinder isolated from the frog sciatic nerve and from fluxes into an intact nerve segment bathed in Ringer. Mean PCa for influx across the isolated perineurium equaled 10.2 +/- 0.6 X 10(-7) cm/s (n = 16) compared with Psucrose = 7.4 +/- 0.4 X 10(-7) cm/s. For efflux, PCa = 27.5 +/- 5.0 X 10(-7) cm/s and Psucrose = 23.2 +/- 4.7 X 10(-7) cm/s. The mean ratio of PCa for efflux to PCa for influx (2.7 +/- 0.5) was not significantly different from the flux ratio for sucrose (3.1 +/- 0.7). No effect on PCa or Psucrose was observed when the calcium concentration in the bath was varied from 0.5 to 20 mM, when Na-free Ringer was perfused, or when ouabain, La3+, or 2,4-dinitrophenol was applied. Asymmetrical fluxes across the perineurial cylinder were due presumably to bulk flow and resultant solvent drag out of the lumen caused by perfusion pressure. Calcium accumulated in the perineurial tissue in a saturable manner with a Km of 80 microM and a Bmax of 0.22 mumol/g wet wt. The half time for calcium exchange from the external medium to the nerve was calculated as 3 h. This long half time and the calcium-sequestering ability of the perineurium suggest that the perineurium can stabilize endoneurial calcium during transient changes in the calcium concentration of plasma. PMID- 3337213 TI - Lentivirus-induced lymphoproliferative disease. Comparative pathogenicity of phenotypically distinct ovine lentivirus strains. AB - For investigation of the pathogenicity of lentivirus strains, which have distinctly different cytopathic phenotypes in synovial membrane cell culture, plaque-purified, lytic, and nonlytic ovine lentivirus (OvLV) isolates were inoculated intratracheally into two groups of neonatal lambs. Twelve lambs were inoculated with a lytic OvLV isolate and 3 lambs each with two nonlytic OvLV isolates. Five control lambs were inoculated with either virus-free medium or were left uninoculated. In 8 of 12 lambs inoculated with a lytic OvLV isolate mild to severe lesions of lymphoid interstitial pneumonia (LIP) and pulmonary lymphoid hyperplasia developed, 6 of 12 lambs had lesions of pulmonary lymph node follicular hyperplasia, 3 of 9 female lambs had lesions of lymphoproliferative mastitis, 3 of 10 lambs had lesions of lymphocytic/plasmacytic synovitis, and 3 lambs had no lesions. In 3 of 6 lambs inoculated with nonlytic OvLV isolates only mild LIP lesions developed, without concurrent mammary gland or joint lesions. Bronchoalveolar lavage samples from OvLV-diseased lambs contained on average 1.5 fold more numbers of total leukocytes, and 4-fold more numbers of lymphocytes, compared with bronchoalveolar lavage samples of normal lambs. Monoclonal antibodies to ovine lymphocyte surface markers showed that the SBU-T8+ lymphocyte (CD 8 equivalent) was the predominant lymphocyte subset (mean of 65% of total lavaged lymphocytes) in bronchoalveolar lavage samples of 3 diseased lambs. Ovine lentivirus was reisolated from multiple tissues of both groups of OvLV-inoculated lambs, but the percentage of individual tissues infected was greater in lambs inoculated with the lytic viral isolate. Control lambs had no lesions and failed to produce OvLV-specific antibodies or yield OvLV from tissues. All OvLV inoculated lambs produced either low or undetectable serum virus neutralizing antibodies. In contrast, lambs inoculated with either lytic or nonlytic OvLV produced precipitating antibodies to OvLV glycoprotein and group-specific protein. However, initial detection of precipitating antibodies to OvLV glycoprotein was earlier (mean, 5.8 weeks after inoculation) in OvLV-infected lambs in which severe lymphoproliferative disease developed and delayed (mean, 10.2 weeks after inoculation) in OvLV-infected lambs with mild or no lesions. Together, these results suggest that lentivirus isolates produced disease in a virus strain-dependent manner and suggest that humoral immune responses against OvLV failed to prevent lesion development in lentivirus-infected lambs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3337216 TI - Phorbol esters inhibit adenylate cyclase activity in cultured collecting tubular cells. AB - Activators of protein kinase C, a calcium- and phospholipid-dependent protein kinase, inhibit vasopressin-stimulated water flow in toad bladder. To determine the biochemical mechanisms of this inhibition, we examined the effects of activators of protein kinase C on arginine vasopressin (AVP)-stimulated adenylate cyclase activity in cultured rabbit cortical collecting tubular cells. The phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA), the diacylglycerol, 1-oleyl-2-acetyl glycerol (OAG), and the diacylglycerol kinase inhibitor, R59022, all rapidly activate protein kinase C in collecting tubular cells. Pretreatment with PMA produces a delayed inhibition (greater than or equal to 4 h) of AVP stimulated adenylate cyclase activity. The 4-h time lag suggests that the effects of protein kinase C are mediated indirectly, possibly as a consequence of stimulating cell proliferation. PMA does not inhibit cholera toxin- or forskolin stimulated adenylate cyclase activity, suggesting an effect on the vasopressin receptor or coupling of the receptor to the stimulatory guanine nucleotide regulatory protein. Neither prostaglandins nor the inhibitory guanine nucleotide regulatory protein appear to mediate this effect. In contrast, treatment with either OAG or R59022 produces a rapid inhibition of both AVP- and forskolin stimulated adenylate cyclase activity suggesting a prominent distal site of action, presumably at the catalytic subunit of adenylate cyclase. The results demonstrate that different activators of protein kinase C inhibit AVP-stimulated adenylate cyclase activity by distinctly different mechanisms possibly by altering the substrate specificity or activating multiple forms of the kinase. These results have important implications when using different activators to study the biological effects of protein kinase C. PMID- 3337215 TI - Na+-Ca2+ exchange in human neutrophils. AB - The pathway for inward Ca2+ movements in isolated human neutrophils was investigated. One-way 45Ca2+ influx into resting, steady-state cells amounted to approximately 6 mumol.l cell water-1.min-1. This uptake can be entirely accounted for on the basis of a carrier-mediated exchange of external Ca2+ for internal Na+. The counter transport exhibited trans stimulation of 45Ca2+ influx by internal Na+ (Km approximately equal to 26 mM) with a Hill coefficient of approximately equal to 2.6. There was substrate saturation by external Ca2+ (Km approximately equal to 0.15 mM) and by external Na+ (Km approximately equal to 30 mM); the two ions competed for the same binding sites. The exchange was noncompetitively inhibited by benzamil (Ki approximately 75 microM) and by some other amiloride analogues bearing a substituent on the terminal nitrogen atom of the guanidino group. Membrane depolarization enhanced the rate of 45Ca2+ entry, suggesting an electrogenic process; this voltage dependence was consistent with a coupling ratio of approximately 3 Na+:1 Ca2+. Hence, the Na+-Ca2+ exchange mechanism of neutrophils displays many features in common with those of other cell types. Studies in cells exposed to the tripeptide N-formylmethionyl-leucyl phenylalanine (FMLP) indicate activation of the counter-transport system by the chemotactic factor. Thus, Na+-Ca2+ exchange may be at least partly responsible for the increase in 45Ca2+ influx and transient rise in intracellular free Ca2+ that are seen following stimulation. PMID- 3337217 TI - Ion transport mediated by copolymers composed of polyoxyethylene and polyoxypropylene. AB - Block copolymers composed of polyoxyethylene and polyoxypropylene were found to increase the influx of Na+ and the efflux of K+ from human erythrocytes. They were, however, ineffective at promoting the transport of Ca2+. The size of the ion fluxes induced by the copolymers correlated with their efficacy in stimulating inflammation. These compounds were also found to induce conductance increases in planar lipid bilayers in a nonvoltage dependent and nonstepwise manner. In both experimental systems, ion transport was facilitated only under temperature and ionic-strength conditions in which the polymers form aggregates in aqueous solution. In neither system did the concentration dependence of transport activity exhibit a pronounced cooperativity. These observations are consistent with the view that aqueous monomers of these surface active agents partition into the membrane, where they facilitate the conductive movement of monovalent cations by means of a carrier type mechanism. As a novel class of ionophores, these substances are of practical interest because they can be water soluble and are potentially reversible. PMID- 3337218 TI - A microelectrometric titration method for measurement of total intracellular Cl- concentration. AB - A microelectrometric titration method is described to measure picomole amounts of Cl- present in solutions at micromolar concentrations. This method was used to measure total intracellular chloride concentration ([Cl-]i) in leukocytes. Through the use of submicroliter samples, [Cl-] can be measured in the range of 5 500 microM. There is no measurable interference from other ions normally present in the cell and no intracellular ion is falsely measured as Cl-. [Cl-]i determined by the conventional coulometric titration and the new microelectrometric titration method was the same. Among the commonly used substituting anions, thiocyanate was the only one falsely measured as Cl- and should be avoided in experiments using this method. Because only picomole amounts of Cl- are required, measurements of intracellular pH and total concentrations of other intracellular ions can be done in the same lysate of as few as 5 X 10(5) cells. This feature should make it possible to study the time course of changes in [Cl-]i together with measurements of other intracellular ions following various physiological or experimental maneuvers. PMID- 3337219 TI - Eicosanoid metabolism in cerebromicrovascular endothelium. AB - Cultured murine cerebral microvessel endothelia produce predominantly prostacyclin and prostaglandin (PG) E2 when exposed to trace amounts of arachidonic acid. At higher concentrations of arachidonate or with ionophore A23187, they produce more PGE2 than prostacyclin and additionally make PGF2 alpha and small amounts of eicosanoids comigrating with hydroxylated derivatives of arachidonate. Endothelia grown on micropore filters release prostaglandins from both apical and basal surfaces; however, the ratio of basal to apical release is as high as 4:1. This polarity suggests that cerebral endothelial prostaglandins can interact with neighboring cells of the vessel wall and brain parenchyma, where they may play important roles in the control of cerebrovascular tone and neuroglial function. These eicosanoids also are produced by mouse brain microvessels, but the major microvessel product is 12-hydroxyeicosatetraenoic acid. This suggests that 12-hydroxyeicosatetraenoic acid may be abundant in brain injuries after arachidonate release. Cultured cerebral endothelia rapidly convert 12-hydroxyeicosatetraenoic to more polar metabolites and thus may prevent the accumulation of this potentially deleterious hydroxyacid. PMID- 3337220 TI - Characterization of [3H]nifedipine binding to intact vascular smooth muscle cells. AB - Specific binding of the dihydropyridine Ca2+ antagonist [3H]nifedipine to dispersed smooth muscle cells of the porcine coronary artery was investigated and the findings were compared with the binding to microsomes of smooth muscles. Specific binding to intact cells was saturable and reversible. The dissociation constant was 1.93 +/- 0.42 nM and the maximal binding capacity was 59.6 +/- 12.4 fmol/10(6) cells, as assessed by Scatchard analysis of the equilibrium binding at 25 degrees C. The Kd value with intact cells was slightly higher than that observed with microsomes. Specific binding of [3H]nifedipine to intact cells was completely displaced by unlabeled dihydropyridine derivatives. Among other Ca2+ antagonists, verapamil and d-cis-diltiazem partially and flunarizine completely inhibited the binding. In the case of microsomes, d-cis-diltiazem stimulated the binding of [3H]nifedipine. These results suggest that there may be multiple binding sites for different subclasses of Ca2+ antagonists. Polyvalent cations had no effect on the binding to intact cells. In the case of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-treated microsomes, the addition of CaCl2 and BaCl2 increased the Bmax, but the Kd value remained unchanged. MnCl2 and CdCl2 had stimulatory or inhibitory effects, depending on the concentrations, whereas LaCl3 had no effect. The effect of membrane depolarization on the binding was also examined. When the intact cells were incubated in high [K+]o solution for 60 min, the Kd was lowered to 1.4 nM from the control value of 2.0 nM, thereby indicating that [3H]nifedipine binds to Ca2+ channels, with a higher affinity, at depolarized states. PMID- 3337222 TI - Intercellular communication between ciliated cells in culture. AB - Cultured mammalian ciliated cells from the respiratory tract respond to mechanical stimulation of their cell surface by displaying a rapid transient increase in beat frequency. Surrounding adjacent and more distal neighboring ciliated cells display a similar frequency response after a short delay that is proportional to their distance from the stimulated cell. To characterize the progression of this communicated response we developed an automated computer assisted image-analysis system to examine high-speed films of responding cells. Transmission of the frequency response between cells occurs at 0.63 cells/s at 25 degrees C and 1.54 cells/s at 37 degrees C. We have also confirmed that gap junctions exist between cells in both epithelial explants and outgrowths and that adjacent or nonadjacent ciliated, as well as nonciliated, cells are electrically coupled. We postulate that mechanical stimulation and intercellular communication provide a mechanism to regulate beat frequency between ciliated cells in order to facilitate efficient ciliary function and mucus transport. PMID- 3337221 TI - Immune-related intestinal Cl- secretion. I. Effect of histamine on the T84 cell line. AB - The mast cell mediator, histamine, induces a rapid and transient increase in chloride secretion across monolayers of the human colonic epithelial cell line, T84. Threshold stimulation occurred at 3 X 10(-6) M histamine and a maximal effect at 10(-4) M. The effect was reproduced by the H1 agonists 2 methylhistamine and 2-pyridylethylamine, but not by the H2 agonists 4 methylhistamine and dimaprit, suggesting the involvement of an H1 receptor. Additionally, histamine's action was inhibited by an H1 antagonist, diphenhydramine, but not by an H2 antagonist, cimetidine. Histamine treatment increased free cytosolic calcium levels, but not those of adenosine 3',5'-cyclic monophosphate (cAMP) or guanosine 3',5'-cyclic monophosphate (cGMP). The mechanism of chloride secretion induced by histamine resembled that of carbachol, in that both 1) were associated with an increase in free cytosolic calcium, 2) had a site of activation at a basolaterally localized K+ channel, and 3) were potentiated by both cAMP- and cGMP-mediated secretagogues. These results suggest that histamine may act as an intestinal secretagogue via direct interactions with epithelial cells. PMID- 3337223 TI - Cross-bridge phosphorylation and regulation of latch state in smooth muscle. AB - We have developed a minimum kinetic model for cross-bridge interactions with the thin filament in smooth muscle. The model hypothesizes two types of cross-bridge interactions: 1) cycling phosphorylated cross bridges and 2) noncycling dephosphorylated cross bridges ("latch bridges"). The major assumptions are that 1) Ca2+-dependent myosin phosphorylation is the only postulated regulatory mechanism, 2) each myosin head acts independently, and 3) latch bridges are formed by dephosphorylation of an attached cross bridge. Rate constants were resolved by fitting data on the time courses of myosin phosphorylation and stress development. Comparison of the rate constants indicates that latch-bridge detachment is the rate-limiting step. Model simulations predicted a hyperbolic dependence of steady-state stress on myosin phosphorylation, which corresponded with the experimental observation of high values of stress with low levels of phosphorylation in intact tissues. Model simulations also predicted the experimental observation that an initial phosphorylation transient only accelerates stress development, with no effect on the final steady-state levels of stress. Because the only Ca2+-dependent regulatory mechanism in this model was activation of myosin light chain kinase, these results are consistent with the hypothesis that myosin phosphorylation is both necessary and sufficient for the development of the latch state. PMID- 3337224 TI - Comparative assessments of objective peak-detection algorithms. II. Studies in men. AB - The performances of eight currently available computerized pulse-detection algorithms were compared on signal-free noise and physiological luteinizing hormone (LH) time series. Signal-free noise was made to vary from 4 to 36% for Gaussian and empirical distributions. Physiological LH data were obtained by immunoassay of blood samples withdrawn every 5 min for 24 h in 8 healthy men, so that the data sets could be emended to simulate varying sampling intensities. Whenever possible, programs were tested at a presumptive 1% false-positive rate. In relation to signal-free noise, the Santen and Bardin program and its modification manifested elevated false-positive rates when the intraseries coefficients of variation increased. The Regional Dual-Threshold program yielded a 1% false-positive rate except on simulated series with high variance. The Cluster and Detect programs both approximated a 1% false-positive rate and the Ultra program approximated a 2.3% false-positive rate throughout the entire range of variance tested. In regard to physiological LH data, all algorithms disclosed a significant impact of sampling intensity on estimates of LH pulse frequency. Sampling-intensity dependent estimates of LH peak frequency by three of the eight programs (Ultra, Cluster, and Detect) were statistically indistinguishable from each other but distinct from the five other programs tested. Furthermore, when judged in relation to their ability to identify individual peaks, the three congruent programs were minimally distinguishable (McNemar's test). Rather, these programs identified the same particular peaks (as defined by concordance of peak maxima) at least 72% of the time. PMID- 3337225 TI - Regional lactate production in early canine endotoxin shock. AB - High serum lactate may not reflect the severity of endotoxin shock: the lactate load could even be formed immediately after the endotoxin challenge. During the first 30 min after endotoxin injection (Escherichia coli; 1.5 mg/kg iv) into anesthetized dogs (4 mg.kg-1.h-1 etomidate, n = 19) we studied arterial lactate concentration; contributions of portal and splanchnic (n = 6), renal and pulmonary (n = 7), and femoral (n = 6) vascular beds to the early lactate rise; and regional O2 extraction and blood flow (microspheres). In control dogs (n = 5, no endotoxin), we found no significant hemodynamic and biochemical changes. Endotoxin caused an immediate decrease in blood pressure, cardiac output, and organ perfusion, followed by recovery after approximately 5 min to approximately 75% of preshock values at t = 30 min (except for renal blood flow, which remained low). Arterial lactate concentration started to increase almost immediately after endotoxin and increased rapidly until t = 15 min (to 300%) and then leveled off, but in spite of the hemodynamic recovery it remained elevated. A major part of the early increase in lactate concentration can be explained by splanchnic lactate production. The total splanchnic bed released more lactate than the portal bed, indicating that the liver produces lactate. We conclude that the lactate concentration later in canine endotoxin shock depends on events that occur during early shock in which the liver may play a crucial role. PMID- 3337226 TI - TeBG- and CBG-bound steroid hormones in rabbits are available for influx into uterus in vivo. AB - The metabolic clearance rate (MCR) of gonadal or adrenal steroid hormones in rabbits often does not bear the expected inverse relationship with hormone binding to testosterone-binding globulin (TeBG) or corticosteroid-binding globulin (CBG). This suggests TeBG or CBG may not impede steroid hormone delivery to tissues. The effects of rabbit plasma proteins on the influxes of 3H-labeled steroids from the circulation into the rabbit uterus were measured in vivo using a tissue sampling single-injection technique. In the absence of plasma proteins, estradiol (E2) and testosterone (T) were freely diffusible through the uterine microvasculature (i.e., extraction greater than 80%). The extractions of dihydrotestosterone (DHT) and corticosterone (B) ranged from 60 to 72%, while that of cortisol (F) was reduced at 40%. Rabbit serum exerted no inhibition of the influxes of the steroids tested. The influxes of T and B greatly exceeded the rates that would be expected if only the free and albumin-bound fractions estimated in vitro were diffusible in vivo. However, the extraction of [3H]corticosteroid-binding globulin or bovine [3H]albumin were low, consistent with little, if any, extravascular uptake of the plasma proteins. The results indicate both albumin-bound and globulin-bound steroid hormone are available for transport into the uterus in the rabbit in vivo without significant exodus of the plasma protein, per se. PMID- 3337227 TI - LH subunit mRNA concentrations during LH surge in ovariectomized estradiol replaced rats. AB - In cycling rats, pituitary concentrations of luteinizing hormone (LH) beta subunit mRNA increase two- to threefold before the afternoon proestrus LH surge without a corresponding increase in alpha-subunit mRNA. Estradiol (E2) treatment is known to allow expression of daily LH surges in ovariectomized (OVX) rats, and the timing, magnitude, and duration of LH secretion is similar to the LH surge on proestrus. The present study was conducted to examine whether the regulation of LH subunit mRNAs during the LH surge in OVX-E2-treated rats is similar to that present on proestrus. Female Holtzman rats were OVX and Silastic implants containing E2 were inserted subcutaneously under ether anesthesia. Some animals received bromocriptine (0.6 mg sc, twice/day beginning 1 h before surgery). On the 2nd day after surgery, groups of animals (n = 4-10/group) were decapitated at intervals between 1000 and 2100. LH and prolactin (PRL) levels were measured in trunk blood. LH subunit mRNA concentrations in the pituitaries were measured by dot-blot hybridization assay. In OVX-E2 rats the LH surge occurred at 1830 and was accompanied by a selective twofold increase in alpha-subunit mRNA (from 266 +/- 18 to 459 +/- 61 pg cDNA bound/100 micrograms pituitary DNA) and maximum values were present at 1730. LH beta-subunit mRNA (m = 29 +/- 1 pg cDNA bound/100 micrograms pituitary DNA) was unchanged throughout the day. Bromocriptine treatment resulted in the suppression of serum PRL (m = 23 +/- 2 ng/ml) and the LH surge was delayed by 1-1.5 h and somewhat blunted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337228 TI - Effects of rectal distension on the sphincter ani externus and levator ani muscles in cats. AB - The response characteristics of levator ani (LA) muscles to rectal distension and its rectified and integrated EMG activity was recorded and compared with the responses of the sphincter ani externus (SAE) to the same stimuli. Experiments were performed in 42 cats anesthetized with chloralose (70 mg/kg) dissolved in a 25% urethan-saline solution. Fast (about 1-2 s) rectal distension (10-40 ml of air were injected into a rubber balloon in the rectum, reaching pressures of up to 80 mmHg) produced a reflex contraction of both LA and SAE muscles. Sustained distension elicited a sustained discharge from the LA muscles that endured for the duration of the distension, up to 2-3 min. These changes were observed in 75% of 210 trials. EMG activity increased from 30 to over 600% of base-line levels, with the majority, 65% of trials, showing greater than 100% increase. In contrast to these excitatory responses of the LA muscles, SAE responded to sustained rectal inflation with inhibition of ongoing activity, an inhibition that could reach muscular silence. Fast intermittent distension, one every 2-3 s, however, produced an increase in the level of activity of the SAE. Analysis of the EMG activity preceding defecation revealed an increase of LA activity 1-2 min before actual expelling. We believe this result to be consistent with the hypothesis that these muscles may contribute to anorectal evacuation. In the anesthetised animal, during the passage of solid material through the anus, the SAE showed increased activity. We believe this to be the result of a local phenomenon, the development of a tonic stretch reflex in the SAE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337229 TI - Electrophysiological analysis of responses to intrinsic nerves in circular muscle of opossum esophageal muscle. AB - The nerve-mediated responses to electrical field stimulation (EFS) along the opossum esophageal circular smooth muscle were studied with the sucrose-gap recording technique. Strips from 1-2, 4-5, 7-8, and 10-11 cm above the lower esophageal sphincter were stimulated with short-train (300 ms) and long-train (3 s) durations at 29 degrees C. The response always consisted of a hyperpolarization [inhibitory junction potentials (IJP)] followed by an "off depolarization" often associated with spike potentials and mechanical contraction. Proximal to distal differences in the characteristics of the evoked responses were found, i.e., increasing amplitude, duration and time to peak hyperpolarization of the IJP, increasing latency, and amplitude of the off depolarization. Neither atropine, scopolamine, physostigmine, nor guanethidine altered these characteristics substantially. Circular strips of muscularis externa, studied in the organ bath at 37 degrees C using 10-s EFS trains at 5-40 pps, produced off contractions, enhanced by physostigmine and reduced by atropine. High-frequency stimulation occasionally initiated small persistent intrastimulus ("on") responses; some were sensitive to cholinergic agents, but there was no gradient in the delay in their onset. Atropine-insensitive and tetrodotoxin-potentiated transient on responses were occasionally detected. We conclude that only the noncholinergic, nonadrenergic innervation provides a functional intrinsic innervation directly to the opossum esophagus circular smooth muscle when nerves are activated by EFS. PMID- 3337230 TI - Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage? AB - The role of leukotriene (LT) C4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis [4-bromo-2,7-dimethoxy-3H phenothiazin-3-one (L651,392), 3-amino-[m-(trifluoromethyl)-phenyl]-2-pyrazoline hydrochloride (BW755c), and dexamethasone] and agents that have previously been shown to reduce ethanol-induced damage [prostaglandin E2, 2-decarboxy-2 hydroxymethyl-15-deoxy-16RS-hydroxy-16- methyl prostaglandin E1 (Rioprostil), FPL52694] prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC4 synthesis. LTC4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethasone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. LTC4 release from hemorrhagic tissue was not significantly increased above that from samples of nonhemorrhagic tissue from the same stomachs. Furthermore, changes in LTB4 synthesis paralleled the changes in LTC4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. Such treatment resulted in significant increases in LTC4 synthesis on both sides of the stomach (compared with controls), although the increase on the challenged side was significantly greater than that on the nonchallenged side. These studies, thus, confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC4 synthesis does not confer protection to the mucosa, suggesting that LTC4 does not play an important role in the etiology of ethanol-induced gastric damage. PMID- 3337231 TI - Absorption and transport of milk calcium by infant rats. AB - All previous studies of Ca absorption in the developing animal have used simple salts of Ca. The aims of the current study are 1) to determine the predominant form of Ca in rat milk and 2) to compare the absorption of milk Ca and CaCl2. In vivo-labeled rat milk was obtained by injecting lactating dams with 45CaCl2. Distribution of 45Ca in the cream, whey, and casein fractions was determined by differential centrifugation, the values being 0.3, 5, and 95%, respectively. To study Ca absorption, rats aged 14 and 28 days received either 45Ca-milk or 45CaCl2 by intragastric intubation. At 14 days, transport of milk Ca into the carcass was significantly slower than that of CaCl2, although by 6 h postintubation both had plateaued at approximately 92% of dose. At 28 days, the time course of transport was the same for the two forms of Ca, and the plateau was not significantly different from that at 14 days. In the younger animals, more Ca from milk than from CaCl2 was retained in gastrointestinal tissue. Quantitation of 45Ca in various segments of the gastrointestinal tract showed that the greater retention of milk Ca occurred in the stomach, the duodenum, and the distal jejunum. We conclude that milk Ca is efficiently absorbed by the suckling rat, possibly in a protein-bound form. The mechanism of the absorptive process awaits further investigation. PMID- 3337232 TI - Increased responsiveness of jejunal longitudinal muscle in Trichinella-infected rats. AB - We examined in vitro changes in contractility of jejunal longitudinal muscle strips in rats infected with the nematode parasite Trichinella spiralis. Length passive tension relationships were unchanged. However, muscle from infected rats on days 5 and 6 postinfection (PI) generated maximal active tension induced by carbachol at significantly less stretch (39.9 +/- 1.0 and 34.3 +/- 6.3%, respectively) than control tissues (66.0 +/- 2.3%). In infected rats on day 5 PI, the maximum tension generated by carbachol (1.6 +/- 0.4 g/mm2) and by 5 hydroxytryptamine (5-HTP) (2.6 +/- 0.1 g/mm2) was significantly greater than in control tissue (0.5 +/- 0.2 g/mm2). On removal of calcium from the medium, responses of muscle from control and infected rats were reduced in a proportionate manner. The increased responsiveness to carbachol and 5-HTP was maximal by day 5 PI and was associated with a decrease in the ED50 value for 5 HTP but not for carbachol. All changes were reversed by 23 days PI. These results indicate that T. spiralis infection in the rat is associated with alterations in jejunal longitudinal smooth muscle function. PMID- 3337233 TI - Evaluation of myosin light chain phosphorylation in isolated pancreatic acini. AB - The role of contractile proteins in secretory granule exocytosis was evaluated by determining whether myosin light chain phosphorylation was altered during stimulation of secretion in mouse pancreatic acini. Acinar myosin was purified by extraction into isosmotic sucrose solution containing 40 mM pyrophosphate followed by ammonium sulfate precipitation and Sepharose 4B-CL chromatography. Myosin was eluted as a single peak of K+-EDTA ATPase activity and was purified over 2,000-fold to a final ATPase specific activity of 0.96 mumol.min-1.mg protein-1. Three major myosin subunits of apparent Mr of 200,000, 20,000, and 17,000 were present in the purified myosin preparation. A fourth protein of Mr 21,000 was also present. Purification of myosin from 32P-labeled acini revealed the Mr 200,000, 21,000, and 20,000 proteins to be heavily labeled. The effect of cholecystokinin octapeptide (CCK-8) on myosin phosphorylation was studied after isolation of myosin from 32P-labeled acinar lysates by immunoprecipitation. Treatment of acini for 1-10 min with a concentration of CCK-8 that gives a maximal secretory response caused a 25-40% increase in light chain labeling. Treatment with a supramaximal CCK-8 concentration produced a 50-80% increase in light chain labeling. Phosphorylation of myosin heavy chain was not significantly affected by secretagogue treatment. These results indicate that stimulation of pancreatic acinar secretion is accompanied by an increase in myosin light chain phosphorylation. PMID- 3337235 TI - Active calcium transport by intestinal endoplasmic reticulum during maturation. AB - Calcium uptake by intestinal endoplasmic reticulum was determined during maturation in the rat. Calcium uptake was enhanced severalfold by the presence of ATP in suckling, weanling, and adolescent rats. Uptake values were higher during early life and decreased gradually with age. Calcium uptake represented transport into the intravesicular space of the microsomes as evident by marked decrease in the uptake of 0 degrees C compared with values at 25 degrees C and by rapid release of intravesicular calcium by the ionophore A23187. Calcium uptake was dependent on magnesium and media pH and was inhibited by vanadate. Sodium oxalate enhanced calcium uptake. Oligomycin and sodium azide did not inhibit calcium uptake by microsomes, suggesting that calcium uptake represents a property of the microsomes rather than mitochondrial uptake. Initial rate uptake was linear up to 30 s. Maximal uptake occurred at pH 7.2. Kinetic studies revealed a high affinity, high-capacity system in microsomes from suckling rats (Vmax 2.26 +/- 0.2 nmol.mg protein-1.15 s-1 and Km 0.56 +/- 0.01 microM) compared with a low capacity system in microsomes from adolescent rats (Vmax 0.72 +/- 0.1 nmol.mg protein-1.15 s-1 and Km 0.69 +/- 0.02 microM). These findings suggest that the endoplasmic reticulum of the enterocyte may play a major role in regulating intestinal cytosolic calcium homeostasis during early development. PMID- 3337234 TI - Influence of hormones on glycogen and glucose metabolism in embryonic chick intestine. AB - Previous studies on the development of embryonic intestine in vitro have revealed a stimulation of epithelial differentiation by the hormones hydrocortisone (HC) and thyroxine (T4). To determine whether these hormones also influence epithelial metabolism, duodena from 14-day-old chicken embryos were cultured for 72 h in the absence of hormones (controls) or in the presence of 1 nM T4 or 1 microM HC. In control cultures, glycogen accumulated within the duodenal epithelium to the level found at 17 days in vivo. T4 reduced glycogen accumulation to 34% of control values, whereas HC increased epithelial glycogen content by 45%. These hormonal effects were due, in part, to modulation of glycogen degradation. In T4 cultures, glucose oxidation activities within the epithelial layer and submucosal tissue were 300 and 140% of control values, respectively, and glucose utilization (removal from the culture medium) was increased. HC significantly decreased both glucose oxidation activity within the submucosal tissue and glucose utilization. These results are consistent with the hypothesis that HC regulates the early phase of epithelial differentiation that is characterized by low metabolic rate and accumulation of energy stores, whereas T4 elicits the prehatching phase of differentiation that is correlated with an increase in metabolic rate and utilization of stored products. PMID- 3337236 TI - Effects of alterations in bolus viscosity on esophageal peristalsis in humans. AB - The effect of increased bolus viscosity on esophageal peristaltic function was studied in six healthy volunteer subjects. Intraluminal pressure events were measured with an infused catheter system and lower esophageal sphincter pressure was monitored continuously with a Dent sleeve. Boluses with viscosities of 2.5, 8.7, 48, and 860 centipoise (cP) were compared with a water bolus. Increasing bolus viscosity to 48 and 860 cP elicited a slowing of wave velocity, an increase in wave duration, and a prolongation of lower esophageal sphincter relaxation. The initial change noted at lower viscosities was an increased duration of contraction wave. Maximal changes were noted at the 48 cP bolus. In conclusion, increased bolus viscosity significantly alters human esophageal peristalsis. These changes may be mediated by esophageal stretch reflexes or by the intrinsic properties of the esophageal musculature or both. PMID- 3337237 TI - Characteristics of putrescine uptake in isolated rat enterocytes. AB - Polyamines are necessary for the growth of eukaryotic cells and are supplied either by new synthesis or cellular uptake. To our knowledge, no information is available on polyamine uptake by gastrointestinal cells. In the current study, isolated villous enterocytes from the rat accumulated putrescine to an eightfold concentration gradient. Uptake was temperature dependent, saturable, and inhibited by 1 mM KCN. Kinetic analysis showed a Km of 1.23 X 10(-5) M and a Vmax of 2.60 X 10(-10) mol.10(6) cells-1.15 min-1. Enterocytes from the distal one fourth of the gut showed the highest rate of uptake. Putrescine uptake was inhibited by cadaverine and spermine but not by the amino acids asparagine, AIB, or leucine. Sodium replacement by choline, lithium, N-methyl-D-glucamine, or tetramethylammonium significantly inhibited uptake, but replacement of Na+ by sucrose or mannitol was without effect. The inhibition observed was believed to be due to the ability of the cations to interact in some way with the carrier. Neither ouabain nor digitoxigenin had any effect on uptake. These data indicate that putrescine is accumulated by villous enterocytes by a carrier-mediated process that does not appear to involve Na+ contransport. PMID- 3337239 TI - Secretagogues activate chloride transport pathways in pancreatic zymogen granules. AB - The membrane permeability of pancreatic zymogen granules was evaluated in vitro with granules isolated from rats in different secretory states: 1) untreated, 2) pretreated with a muscarinic antagonist, 3) pretreated with a muscarinic and an adrenergic antagonist, 4) pretreated as in 3 and then stimulated with the secretagogue cholecystokinin 4 min before death, and 5) pretreated as in 3 and then stimulated with the secretagogue secretin 4 min before death. Granules isolated from untreated rats had variable ionic permeabilities but in general possessed both chloride conductance and electroneutral exchange pathways with low permeabilities to alkali metal ions. In contrast, granules from animals pretreated with secretory antagonists had very low ion permeabilities to both inorganic anions, such as chloride, and alkali metal ions. Injection of the peptide secretagogues cholecystokinin or secretin resulted in a relatively fast (within 4 min) activation or induction of high chloride permeabilities through both chloride conductance and chloride/hydroxide (or chloride/bicarbonate) exchange pathways. In addition, the secretagogues increased the cation permeability of the granule membrane, which exhibited a distinct potassium selectivity. Chloride conductance has been postulated to play a major role in fluid secretion coupled to exocytosis of macromolecules [R. C. DeLisle and U. Hopfer, Am. J. Physiol. 250 (Gastrointest. Liver Physiol. 13): G489-G496, 1986]. These results demonstrate that granules may actively participate in the secretory process and suggest that some of the physiological targets in the cascade of events leading to secretion are anion and cation transporters in the zymogen granule membrane. PMID- 3337240 TI - A standard nomenclature for structures of the kidney. The Renal Commission of the International Union of Physiological Sciences (IUPS). PMID- 3337238 TI - Development of gastrin synthesis and posttranslational processing mechanisms in rats. AB - To examine the ontogeny of gastrin synthesis and posttranslational processing mechanisms, we utilized region-specific antisera to determine the factors that regulate the contents of gastrin and its precursors in the stomachs of developing rats. Gastrin content increased gradually from birth to a peak at 5 wk of age, after which there was a slight decrease to levels observed in mature animals. Unlike gastrin, glycine-extended precursors of gastrin (G-Gly) increased abruptly in the first day of life but thereafter increased at a steady state. Dexamethasone treatment and early weaning (at 11 days of age) rapidly increased gastrin content, whereas G-Gly content was decreased. On weaning animals to adult rat chow abruptly at an age (18 days) when the corticosteroid surge associated with the weaning process had already occurred, evidence for increases in both gastrin and G-Gly content were observed 7 days later. In contrast, administration of dexamethasone to 18-day-old rats enhanced gastrin content to a greater extent than G-Gly. These results suggest that the natural surge in corticosteroids associated with weaning may enhance gastrin amidation activity, whereas the concomitant dietary changes may exert a stimulatory effect of gastrin synthesis. PMID- 3337241 TI - Renal brush-border chloride transport mechanisms characterized using a fluorescent indicator. AB - Cl transport mechanisms in brush-border membrane vesicles (BBMV) isolated from rabbit renal cortex were characterized using the Cl-sensitive fluorescent indicator 6-methoxy-N-[3-sulfopropyl]quinolinium (SPQ). In control experiments using 36Cl, SPQ did not itself alter rates for Cl transport. Cl fluxes (JCl) in nanomoles per second per milligram vesicle protein in response to gradients of Cl and other ions were calculated from the SPQ fluorescence time course, fluorescence vs. [Cl] calibration, and BBMV glucose space (microliter/mg protein). For a 50 mM inwardly directed Cl gradient in BBMV (voltage and pH clamped) JCl was 0.26 +/- 0.01 nmol.s-1.mg-1 (mean +/- SD, 4 vesicle preparations). JCl was not altered by a 50 mM inwardly directed Na gradient (0.25 +/- 0.01 nmol.s-1.mg-1) but increased to 0.52 +/- 0.04 nmol.s-1.mg-1 when driven by a 1.5 pH unit inwardly directed proton gradient. The pH driven increase in JCl was blocked by H2DIDS (100 microM, JCl = 0.38 +/- 0.02 nmol.s-1.mg-1). In the absence of a gradient, JCl increased by 64 +/- 4% in the presence of 1 mM formate on both sides of the membrane; the increase was blocked by H2DIDS. JCl increased to 0.38 +/- 0.02 nmol.s-1.mg-1 for a 60-mV K valinomycin diffusion potential (internal positive); the increase was inhibited by the Cl channel blocker diphenylamine-2-carboxylate (DPC, 100 microM, JCl = 0.26 +/- 0.03 nmol.s-1.mg-1). Br and I transport was also blocked by DPC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337242 TI - Renal metabolic/excretory coupling. AB - Renal metabolic/excretory coupling is the enhancement of urinary excretion dependent upon renal metabolism. The nitrofurothiazoles, N-[4-(5-nitro-2-furyl)-2 thiazolyl]formamide (FANFT) and 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), are model compounds used to study metabolic/excretory coupling. FANFT is deformylated to ANFT by renal deformylase enhancing ANFT excretion. In the rat, ANFT excretion after oral FANFT administration was 100-fold greater than ANFT excretion when ANFT was administered. FANFT and ANFT uptake into purified proximal tubules achieved equilibrium within 60 s and was demonstrated in nonviable tubules. FANFT partitioned into oil better than ANFT. Albumin inhibited FANFT and ANFT uptake into oil and decreased tubular uptake by 65%. Tubular FANFT uptake was threefold or greater than that of ANFT uptake with or without albumin. Renal deformylase was predominantly cytosolic and yielded apparent Km and Vmax of 6.7 microM and 6.1 nmol ANFT.min-1.mg protein-1, respectively. Deformylase activity was abolished by boiling, was specific for N-formylated compound, and was not altered by dinitrophenol treatment. Renal metabolic/excretory coupling for FANFT/ANFT combines energy-independent uptake with metabolism (deformylation), resulting in enhanced urinary ANFT excretion. PMID- 3337243 TI - Plasma AVP and renal concentrating defect in chloride depletion metabolic alkalosis. AB - These studies were undertaken to determine the effect of chronic chloride depletion metabolic alkalosis (Cl-DEP-MALK) on water intake, plasma arginine vasopressin (AVP) levels, and renal concentrating ability. Cl-DEP-MALK was induced by feeding a chloride-free diet to rats subjected to gastric drainage and to dogs treated with furosemide. All of the animals developed a urine concentrating defect, polydipsia, and a persistent reduction in plasma osmolality. However, AVP release was not suppressed. The results of osmotic loading experiments in dogs analyzed using either linear or log-linear models have shown that chronic Cl-DEP-MALK significantly alters the relation between plasma osmolality and plasma AVP. In the classic linear analysis the results suggest that Cl-DEP-MALK reduces the plasma osmolality at which plasma AVP can be detected, i.e., reduced "threshold," and increases the slope of the plasma osmolality-to-plasma AVP relation nearly twofold, i.e., increased "sensitivity." Finally, we provide evidence that the concentrating defect is not related to high water turnover or deficient endogenous AVP and is therefore nephrogenic. PMID- 3337244 TI - Glucocorticoids have a different action than aldosterone on target tissue. AB - Studies were performed, using a synthetic glucocorticoid, RU 28362, that has negligible binding to aldosterone receptors, to examine whether the effect of glucocorticoids on the electrical properties of rat distal colon involves a specific mechanism or crossover binding to aldosterone receptor sites. Compared with control, RU 28362, in a dose of 70 micrograms.100 g body wt-1.day-1, increased transepithelial potential differences (VT) twofold and the equivalent short-circuit current (ISC) threefold; epithelial resistance (RT) was reduced 25%. These changes were qualitatively similar to, but less than, the changes induced by the same dose of aldosterone. The effects of dexamethasone in the same dose were indistinguishable from the changes caused by aldosterone. The results of cell-impalement studies corresponded to whole epithelial changes; RU 28362 induced a small increase in basolateral potential difference, from -43 +/- 2 to 45 +/- 1 mV, and a fall in apical potential difference, from 40 +/- 2 to 36 +/- 1 mV, but these effects on cell membrane voltage were less than caused by either aldosterone or dexamethasone. In contrast to the marked inhibitory action of amiloride to reduce VT in aldosterone- and dexamethasone-treated animals, this sodium channel blocker had no effect on VT in RU 28362-treated animals. Similarly, while spironolactone caused marked inhibition of the changes in VT, RT, and ISC induced by aldosterone, the inhibitory action on tissue from RU 28362 treated animals was slight or absent. These results suggest that glucocorticoids have a specific aldosterone receptor-independent action on the electrical properties of the large intestine. PMID- 3337245 TI - Renal nerves in exaggerated water and sodium excretion by hypertrophied kidney of anesthetized rats. AB - The effect of acute renal denervation (RD) on water (V), sodium (UNaV), and potassium excretion (UKV) from the hypertrophied and control kidney was studied in 5-sec-butyl-5-ethyl-2-thiobarbituric acid (Inactin)-anesthetized male rats 7 days after unilateral nephrectomy (Nx) or sham operation (SNx). V, UNaV, and UKV from the hypertrophied kidney were similar before and after RD or sham RD. In contrast, in SNx rats, left RD resulted in an ipsilateral increase in V (from 2.76 +/- 0.39 to 5.31 +/- 0.99 microliters.min-1.g-1), UNaV (from 109 +/- 36 to 857 +/- 331 nmol.min-1.g-1), and UKV (from 144 +/- 44 to 807 +/- 130 nmol.min-1.g 1; P less than 0.05 in all cases). Moreover, renal parameters from the hypertrophied kidney, subjected to either RD or sham RD, were not different from values after RD in SNx rats (V: Nx, sham RD = 5.72 +/- 1.10; Nx, RD = 5.23 +/- 0.66; SNx, RD = 5.31 +/- 0.99 microliters.min-1.g-1; UNaV: Nx, sham RD = 896 +/- 319; Nx, RD = 821 +/- 262; SNx, RD = 857 +/- 331 nmol.min-1.g-1; UKV: Nx, sham RD = 782 +/- 127; Nx, RD = 860 +/- 82; SNx, RD = 807 +/- 130 nmol.min-1.g-1). In additional experiments, integrated renal nerve activity (RNA) to the kidney in Nx and SNx rats was 4.0 +/- 0.3 and 10.7 +/- 0.9 microV (P less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337247 TI - Phase-locked rhythms in periodically stimulated heart cell aggregates. AB - We have studied the effect of injecting a periodic train of current pulses into spontaneously beating aggregates of embryonic chick ventricular heart cells. Over a range of stimulation frequencies around the intrinsic frequency of an aggregate we find one action potential for each stimulus with a fixed latency from each stimulus to the subsequent action potential. For a stimulation frequency higher (lower) than the intrinsic frequency, this corresponds to overdrive (underdrive). At high frequencies of stimulation dropped beats occur leading to complex rhythms analogous to various Wenckebach rhythms observed clinically. At higher stimulation frequencies one can obtain a complete suppression of action potential generation. At low frequencies of stimulation, there are rhythms containing escape beats. Almost every rhythm seen bears a striking resemblance to some cardiac arrhythmia. We present a simple classification scheme that predicts the order of appearance of all the classes of rhythms experimentally observed as one changes the stimulation frequency. We propose that this scheme can be used generally to describe the behavior of other biological oscillators. PMID- 3337246 TI - PAF and PDGF increase cytosolic [Ca2+] and phospholipase activity in mesangial cells. AB - Platelet-activating factor (PAF) and platelet-derived growth factor (PDGF) likely play important roles in glomerular processes. To identify mechanisms of PAF- and PDGF-induced mesangial cell activation, we characterized effects of both agents on cytosolic free [Ca2+] ([Ca2+]f) and phospholipase activation. When cultured rat renal mesangial cells were stimulated by PAF, [Ca2+]f increased (within 10 s) from 110 +/- 6 to 209 +/- 14 nM, due to release of Ca2+ from intracellular storage sites, as well as entry of Ca2+ from external milieu. PAF also rapidly increased free arachidonate, diacylglycerol, and inositol trisphosphate (IP3) levels. PDGF increased [Ca2+]f from 78 +/- 12 to 192 +/- 22 nM, but the time response was different from that seen with PAF. Peak [Ca2+]f increase occurred at approximately 1 min subsequent to stimulation. Like PAF, increased [Ca2+]f was due to release of Ca2+ from intracellular stores and entry from extracellular media. PDGF increased levels of free arachidonate prior to an increase in diacylglycerol levels. PDGF increased inositol bisphosphate and IP3 levels at 2 min but not at 15 s. Thus, PDGF may mediate a phospholipase C-independent activation of phospholipase A2. In permeabilized mesangial cells, IP3 released Ca2+ from nonmitochondrial storage sites. Thus, PAF- and PDGF-induced increases in [Ca2+]f were likely secondary to activation of phospholipase C, resulting in increased levels of IP3. Understanding differences in mechanisms of mesangial cell activation by PAF and PDGF will likely lead to a better understanding of signal transduction pathways and provide insight into the role of these activators in glomerular disease. PMID- 3337248 TI - Time course and determinants of recovery of function after reversible ischemia in conscious dogs. AB - The postischemic recovery of contractile function [measured as systolic wall thickening (WT)] was analyzed in 21 conscious dogs undergoing a 15-min coronary occlusion followed by 7 days of reperfusion (REP). Average WT was still depressed 24 h after REP (85% of base line, P less than 0.001) and returned to base line by 48 h. Analysis of individual dogs, however, revealed marked variability, whereby some recovered completely by 1 h of REP and others required up to 48 h. WT recovered completely within 30 min in dogs with collateral blood flow (CBF) greater than 50% of nonischemic zone flow (NZF) but was still impaired at 24 h (P less than 0.05) in those with CBF less than 25% of NZF. There was a close, curvilinear relation between WT during the first 4 h of REP and transmural CBF, which was described best by an exponential equation WT (as percent of base line) = P0-P1e-P2.CBF(as % of NZF) (r2 = 0.92 at 1 h, 0.76 at 2 h, 0.71 at 3 h, and 0.72 at 4 h), where P0, P1, and P2 are regression coefficients. Importantly, the slope of the regression line was very steep at low CBF, implying that even small differences in CBF produce large differences in postischemic function. Heart rate, systolic pressure, and rate-pressure product during ischemia were also related to WT after REP, but when the effect of CBF was taken into account, the influence of these variables became insignificant. The size of the occluded vascular bed did not correlate with postischemic WT. The presence of hypokinesis or akinesis during ischemia was associated with rapid recovery after REP, but there was no relation between ischemic and postischemic dysfunction when dyskinesis was present during occlusion. Thus, on the average, regional function remains depressed for 24 h after a 15-min ischemic episode, but there is considerable individual variability. This variable rate of recovery is determined primarily by the severity of blood flow reduction during ischemia. Systemic hemodynamics may modulate recovery of function indirectly via their effects on ischemic blood flow. PMID- 3337249 TI - Use of acetylcholine to measure total vascular pressure-volume relationship in dogs. AB - To define total vascular capacitance, we used acetylcholine to arrest the heart and measured mean circulatory filling pressure (MCFP) during controlled hemorrhage and volume loading in 12 splenectomized dogs after ganglion blockade with hexamethonium. We also examined the gross pathological and histological changes in the lungs. Controlled hemorrhage (n = 12) of 5 and 10 ml/kg decreased MCFP from 6.8 +/- 0.1 to 4.9 +/- 0.3 and 3.6 +/- 0.2 mmHg, respectively. Volume loading of 5 (n = 8) and 10 ml/kg (n = 4) increased MCFP to 9.3 +/- 0.2 and 12.1 +/- 0.1 mmHg, respectively. At MCFPs below 5 mmHg, the pressure (P)-volume (V) relationship was not linear [(P = P0ekV, where k is slope of ln (MCFP) vs. V, k = 0.061, R2 = 0.998]. At MCFPs between 5 and 12 mmHg, the pressure-volume relationship was linear (slope = 0.479 mmHg.ml-1.kg-1, R2 = 0.992) and total vascular compliance was 2.09 ml.mmHg-1.kg-1. There were no changes in heart rate, cardiac output, right atrial, pulmonary artery, and pulmonary artery wedge pressures when values at base line were compared with those measured 15 min after each arrest. There were no changes in arterial gas measurements or acid-base balance, and there was no evidence of atelectasis or interstitial or intra alveolar edema. We conclude that the total body pressure-volume relationship in the presence of ganglion blockade had a nonlinear configuration. The use of acetylcholine to arrest the heart, four times with hexamethonium in reflex blocked animals, did not result in changes in hemodynamics or pulmonary function. PMID- 3337250 TI - Effect of sciatic nerve stimulation on pial arterioles in rats. AB - The present study documents the microvascular response of the pial circulation in sensory hindlimb cortex to sciatic nerve stimulation. Rats, anesthetized with alpha-chloralose and urethan, were equipped with closed cranial windows, and pial arteriolar diameter was measured during stimulation of the contralateral sciatic nerve. The effects of varying stimulus frequency, intensity, and duration were examined. Optimal stimulus frequency was 5 Hz, but response diminished significantly beyond 10 Hz. Optimal stimulus intensity was 0.2 V. At higher stimulus strength, arteriolar dilation was reduced, but systemic blood pressure rose significantly. At low stimulus frequency and intensities, pial arterioles responded to stimulation with a consistent pattern: initial delay of 1.4 s followed by abrupt dilation to a peak magnitude, subsequent decline to a lesser but still dilated state, and recovery to a resting diameter after the cessation of stimulation. No consistent response profile was discernible at high stimulus intensity and/or frequency. This vasodilatory response was discretely restricted to a limited number of arterioles, confined to the hindlimb somatosensory cortex as confirmed by sensory evoked response. The response of the pial circulation provides a well-characterized model for analysis of brain microcirculation, which presumably is linked to cerebral metabolism. PMID- 3337251 TI - Effect of intracarotid administration of ouabain in dogs. AB - Recent work has documented both centrally mediated vasoconstriction and, paradoxically, a withdrawal of sympathetic activity in response to cardiac glycosides. In the present study the possibility that these different neurogenic responses might be dose related was investigated by infusing ouabain (5, 10, and 20 micrograms) for 5 min into the right common carotid artery of 51 anesthetized mongrel dogs. Effects on vascular resistance in the isolated, separately perfused but innervated gracilis muscle were measured. A 5-microgram infusion of ouabain (n = 6) produced a prolonged decrease in gracilis vascular resistance (GVR) of 19.4 +/- 5.4% (SE) from 43.4 +/- 6.7 (SE) to 33.7 +/- 4.2 mmHg.ml-1.100 g muscle.min (resistance units, RU). This vasodilatory response was not present in nine additional dogs following denervation of the carotid bifurcation. A 10 microgram infusion had no significant effect on GVR (n = 5), but the 20-microgram infusion of ouabain (n = 8) caused a rapid increase in GVR from 42.1 +/- 5.0 to 47.6 +/- 5.7 RU, an increase of 14.4 +/- 5.6%, which was not influenced by denervation of the carotid bifurcation (n = 8). This vasoconstriction was transient returning toward the control levels by 20 min following the infusion. These data indicate important dose-related differences in vascular responses to ouabain that are directionally opposite and mediated by separate neurogenic mechanisms. At high doses a centrally mediated vasoconstriction dominates, whereas at low doses carotid bifurcation mediated vascular dilatation occurs. PMID- 3337252 TI - Base-line O2 extraction influences cerebral blood flow response to hematocrit. AB - We have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O2 content (CaO2). In the present study, we tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). E is the ratio of O2 demand (cerebral O2 consumption, CMRO2) to supply (cerebral O2 transport: OT = CBF x CaO2) and is assumed to be inversely related to tissue O2 availability. Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia [arterial CO2 partial pressure (PaCO2) = 15.3 +/- 0.7 mmHg, means +/- SE; n = 7] or hypercarbia (PaCO2 = 62.7 +/- 1.1 mmHg; n = 5), respectively. A second isovolemic exchange transfusion with pure methemoglobin containing adult sheep red cells then raised Hct (to 38.5 +/- 0.5%) with no significant increase in CaO2. PaCO2 was maintained and other variables (oxyhemoglobin affinity, pH, mean arterial blood pressure) with potential effect on CBF did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337253 TI - Cardiac gap junction channel activity in embryonic chick ventricle cells. AB - We have recorded single-gap junction-channel currents from pairs of 7-day chick embryo ventricle cells, using the double whole cell patch-clamp technique. Junctional conductance (Gj) was variable from one preparation to the next, ranging from 0.15 to 35.0 nS. Single-channel conductance (gamma j) of the main junctional channel was 166 +/- 51 pS and was independent of Gj; a second conductance level of 60-80 pS was also seen in favorable records. The transition time from the closed to the open state was 285 +/- 153 microseconds, with some slow transitions lasting 1-5 ms. Channels opened and closed stochastically; Gj could be defined by the product of the number of active channels in the junction (N), the mean open-state probability (Po) of the channels, and gamma j. Channel activity was unaffected by cell membrane potential or by transjunctional potential. Po and Gj were reversibly reduced to low levels by 1-octanol or by elevated [Cai], whereas gamma j was unchanged by these agents. The 60-80 pS conductance mechanism was octanol- and Ca-resistant, but it is not clear whether this represents a subconductance level of the main channel or a separate class of smaller channels. PMID- 3337254 TI - Improved techniques for cardiovascular monitoring in rats as applied during endotoxemia. AB - We describe a new combination of techniques for measurements of systemic blood pressure, central venous pressure, pulmonary arterial (PA) pressure, PA wedge pressure, and cardiac output in the rat. Application of the method to the conscious rat in a septic shock (Escherichia coli endotoxin iv injection) model demonstrated a response pattern of decreased cardiac output and stroke volume, increased total peripheral vascular resistance and heart rate, and transiently decreased systemic arterial pressure. In the pulmonary circulation, a very brief hypertension and a sustained increase in pulmonary vascular resistance were observed, but changes in PA wedge pressure were small. The soft PA catheter (0.3 mm ID, 0.6 mm OD) had no undue effects on cardiovascular function. We suggest that this combined technique could be useful for many cardiovascular studies in the rat, not only as related to shock research. PMID- 3337255 TI - An electronic, negative feedback device to control arterial pressure. AB - Cardiovascular investigations frequently require manipulation of the arterial pressure for assessment of neural reflexes. This has largely been accomplished in the past by a bolus injection or constant infusion of a vasoactive drug. The purpose of the present investigation was to develop a proportional, integrative, negative feedback device capable of controlling arterial pressure in rats by modulating the infusion rate of the vasoconstrictor, phenylephrine. The device was designed to 1) maintain arterial pressure at a constant plateau level above the prevailing control pressure and 2) create linear ramp increases in arterial pressure. We have validated this system with conscious and urethan-anesthetized rats instrumented with arterial cannulas for arterial pressure measurement and aortic or venous cannulas for phenylephrine infusion. When used to create steady state changes in blood pressure at 150 mmHg, the device maintained arterial pressure within +/- 7 mmHg of the desired level for the 20-min experimental periods. When used to create rising arterial pressure ramps (duration: 60 s; magnitude: 30 mmHg), regression analysis of the pressure vs. time relationship indicated that the correlation coefficient was greater than 0.99 in 90% of the trials, indicating a linear ramp. This device will aid in future cardiovascular protocols, especially in the analysis of baroreflex sensitivity. PMID- 3337256 TI - Spontaneous vasomotion in pressurized cerebral arteries from genetically hypertensive rats. AB - Resistance-sized branches of posterior cerebral arteries from Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), spontaneously hypertensive stroke-prone (SHRSP), and antihypertensive-treated SHRSP (SHRSP-TRT) rats were studied in vitro. After the rats were killed, arterial segments were excised, mounted on microcannulas, and pressurized. After equilibration, intravascular pressure was increased in a stepwise fashion from 30 to 150-200 mmHg. All vessels developed a myogenic tone, which resulted in diameter reductions of 31-37% at 100 mmHg when compared with fully relaxed diameters [approximately 200 micron in 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid]. Differences in the extent of tone were not significant between animal groups (P greater than 0.05). Rhythmic vasomotion was present in 94% SHRSP and 100% SHRSP-TRT, 83% SHR, and only 6% of the WKY arteries. At higher pressures, the amplitude of the diameter oscillations decreased and frequency increased. Vasomotion was unaltered by tetrodotoxin or indomethacin, but could be abolished by cooling to 34 degrees C, ouabain (a depolarizing solution containing 125 mM K+), potassium-free physiological saline solution, or by calcium entry blockade with diltiazem or MnCl2. In normally quiescent WKY arteries, vasomotion, which was qualitatively similar to that observed in the hypertensive strains, could be induced by the addition of 5 mM tetraethylammonium chloride. Thus intrinsic oscillations in membrane calcium and potassium conductance may underlie the rhythmic contractile activity of rat cerebral arteries. This property appears to have a major genetic component, the expression of which is relatively independent of blood pressure history and is not related to the myogenic properties of the preparation. PMID- 3337257 TI - Oxygen-saving effect of negative work in dog left ventricle. AB - We compared left ventricular oxygen consumptions (VO2) of contractions performing negative external work (EW less than 0) and positive external work (EW greater than 0) that developed comparable peak systolic pressures in the excised cross circulated dog hearts. We changed the polarity of ventricular work with volume servo-pump and measured both left ventricular VO2 and systolic pressure-volume area (PVA). PVA represents the total mechanical energy generated by contraction and is equal to the area circumscribed by the end-systolic and end-diastolic pressure-volume (PV) relation curves and the systolic PV trajectory. For comparable peak systolic pressures of approximately 90 mmHg, contractions performing negative EW of -834 +/- 327 mmHg.ml.100 g left ventricle-1 had 27 +/- 11% smaller VO2 and 62 +/- 12% smaller PVA than those performing positive EW of 851 +/- 329 mmHg.ml.100 g-1. The smaller VO2 for negative EW could be accounted for by the linear VO2-PVA relation regardless of the polarity and magnitude of work. The results indicate that negative work can save VO2 of contractions to develop a given peak systolic pressure. PMID- 3337258 TI - Pressor and intestinal vascular bed responses to vasopressin after cholinergic blockade. AB - Superior mesenteric arterial flow, aortic blood pressure, and heart rate were recorded, and plasma arginine vasopressin (AVP) concentrations were measured in conscious unrestrained cats during intravenous infusions of AVP (0.1-8.1 mU.kg-1. min-1). Responses to AVP were studied when autonomic nervous system (ANS) function remained intact and when the cholinergic limb of the system had been antagonized by methscopolamine nitrate (0.5 mg/kg) or by pirenzepine (60 micrograms/kg). Elevations in the circulating levels of AVP to approximately 30 and 600 fmol/ml in cats with intact ANS function were associated with decreases in superior mesenteric arterial conductance (SMAC, ml.min-1.kg-1.mmHg-1) of approximately 9 and 50%. The relationship between the dose of AVP and the decreases in SMAC for methscopolamine-treated cats was displaced slightly but significantly to the left of that for intact cats. The relationship between the dose of AVP and the increases in arterial pressure for methscopolamine-treated cats was also significantly displaced to the left of that for intact cats; however, the magnitude of the displacement was much greater than that for the dose-conductance relationship. In contrast to the findings with methscopolamine, pirenzepine did not significantly influence either the dose-conductance or dose blood pressure response curves. These results are consistent with three conclusions. First, physiologically (less than 30 fmol/ml) and pathophysiologically (less than 600 fmol/ml) relevant concentrations of AVP are capable of inducing intestinal vasoconstriction, even in the presence of intact autonomic function. Second, the cholinergic limb of the autonomic nervous system plays a major role in buffering the vasopressor effects of AVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337259 TI - Developmental changes in regional cerebral blood flow in fetal and newborn lambs. AB - Developmental changes in regional cerebral blood flow (CBF) were determined using radioactively labeled microspheres to measure flow to the cortex, brain stem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs under physiological conditions: 90- to 100-day preterm fetal lambs (n = 14), 125- to 136-day near-term fetal lambs (n = 11), and newborn lambs 5-44 days old (n = 10). We continually monitored heart rate, central venous pressure, and mean arterial blood pressure (MAP) and periodically measured arterial blood O2 and CO2 tensions (PaO2, PaCO2, respectively), pH, hemoglobin, and oxygen saturation (SaO2). The regional CBF measurements (ml.100 g 1.min-1) revealed that in all three age groups the high flow areas are the choroid plexus and caudate nucleus, whereas the lowest flow area is the white matter. There is, however, a different hierarchy of regional CBF in utero (cortex less than cerebellum and brain stem) compared with extrauterine life in the newborn lamb (cortex and cerebellum greater than brain stem). Analysis of regional cerebral oxygen delivery [CBF times arterial oxygen content (CaO2)] demonstrated a progressively increasing oxygen transport to the cortex with increasing gestational maturity and after birth. Oxygen transport to the brain stem, cerebellum, and white matter increased with gestational age, but did not increase after birth. Relationships between regional CBF and natural physiological variations of cardiorespiratory parameters (PaO2, SaO2, CaO2, pH, PaCO2, and MAP) were assessed using regression analysis. Correlations of regional CBF with PaO2 and SaO2 suggest that cerebral perfusion is not primarily determined by CaO2 when variations occur within the physiological range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337260 TI - Contractile properties of single isolated feline ventriculocytes. AB - Isolated single cardiac myocytes are becoming an increasingly popular experimental preparation. To date, however, the mechanical properties of these isolated adult mammalian cardiac myocyte preparations have not been thoroughly evaluated. The aims of this research were to 1) define the basic contractile properties of externally unloaded single feline ventriculocytes, 2) determine their response to standard inotropic stimuli, and 3) determine whether contractile properties vary as a function of cell size. Cell contractions were elicited by field stimulation (1 Hz) and recorded with the use of a photodiode array technique. In the 121 myocytes studied (2 mM Ca2+; 37 degrees C) the maximum extent of shortening averaged 7.5 +/- 0.2% resting cell length (L). The maximum rates of shortening and relengthening were 92 +/- 2.7 and 103 +/- 2.0% L/s, respectively. Elevating the extracellular Ca2+ and paired pulse stimulation increased the magnitude of twitch contractions as well as the rates of shortening and relengthening. The relationship between cell size and contractile performance was assessed in this research either by comparing the contractile properties of large and small myocytes or by plotting specific contractile parameters as a function of myocyte surface area. The results of this research support the idea that single feline ventricular myocytes retain normal contractile capabilities following isolation and respond to inotropic maneuvers in a similar fashion to that observed in multicellular preparations. In addition the present experiments showed that the contractile properties of the myocytes isolated from normal feline hearts are not cell size dependent. PMID- 3337261 TI - Vasomotion in cerebral microcirculation of awake rabbits. AB - Cerebral arterioles of unanesthetized rabbits equipped with chronically implanted cranial windows exhibited spontaneous rhythmic variation in vessel caliber characteristic of vasomotion. This variation was noted in all examined vessels. The vasomotion was independent of arterial blood pressure or respiration. The average frequency was 0.74 cycles/min and was independent of vessel size. The mean amplitude of the oscillations had a statistically significant inverse relationship to vessel diameter (r = 0.69). Vasodilation induced by arterial hypercapnia, topical adenosine, or topical acetylcholine had no significant effect on the frequency or amplitude of vasomotion. Anesthesia significantly reduced the frequency in arterioles of all sizes and markedly reduced amplitude in large arterioles. Topical verapamil resulted in a statistically significant reduction in frequency and in peak amplitude. Variations in vessel diameter occurred simultaneously in arterioles and their companion venules. We conclude that the cerebral microcirculation displays active vasomotion, which is significantly depressed by anesthesia or topical verapamil. The results also suggest that vasomotion is probably controlled by local factors. PMID- 3337262 TI - Effects of thyroid state on venous compliance and left ventricular performance in rats. AB - The cardiovascular system of hypothyroid, normal, and hyperthyroid rats was studied by evaluation of the peripheral venous circulation and left ventricular (LV) systolic and diastolic performance in rats. Cardiac index (CI) and CI during a volume load were measured in open-chest rats. When compared with control, hypothyroid rats showed a decrease in heart rate, aortic pressure, LV systolic pressure, first derivative for LV pressure (LV dP/dt), CI, and CI during a volume load. LV pressure-volume relation was shifted to the right, muscle stiffness was unchanged, and LV relaxation was prolonged. There was a decrease in mean circulatory filling pressure (MCFP) to 6.3 +/- 0.2 from 7.6 +/- 0.2 mmHg in control rats. This was associated with an 11% decrease in unstressed vascular volume and 12% decrease in total blood volume but no change in venous compliance. In hyperthyroid rats there was an increase in heart rate, LV systolic pressure, LV dP/dt, CI, and CI during a volume load. LV chamber stiffness was increased, but muscle stiffness and LV relaxation were unchanged. There was an increase in MCFP to 9.5 +/- 0.3 mmHg and a decrease in venous compliance to 2.65 +/- 0.12 compared with 3.20 +/- 0.09 ml.mmHg-1.kg-1 in control rats. Unstressed vascular volume and total blood volume were unchanged. In conclusion, hyperthyroid rats have augmented LV systolic function and altered diastolic function which, combined with changes in the venous circulation, result in increased venous return and thus cardiac output. In hypothyroid rats both LV systolic and diastolic function are altered. When combined with changes of the venous circulation the changes result in a decrease in cardiac output. PMID- 3337263 TI - Initial equilibration of albumin in rabbit hindpaw skin and lymph. AB - We compared initial plasma to extravascular and plasma to lymph equilibrations of 125I-labeled rabbit albumin in hindpaw heelskin of anesthetized rabbits during control conditions, increased venous pressure (IVP), and intra-arterial infusions of papaverine or bradykinin. Plasma tracer concentrations were maintained constant during the experiments. Control prenodal lymph specific activity relative to plasma specific activity (L*/P*) was significantly greater (P less than 0.01) than extravascular specific activity relative to plasma specific activity (M/P) following 3, 5.5, and 11 h of tracer infusion. Papaverine increased lymph flow and lymph albumin flux (LCL) 2.4-fold, without significantly changing the extravascular albumin mass (MA). IVP increased LCL 2.5-fold and decreased MA 25%. L*/P* at 3 h was twice control following papaverine. M*/P* at 3 h was not significantly affected by papaverine or IVP. Bradykinin increased LCL 10-fold and MA 2.3-fold. L*/P* and M*/P* were 3.1 and 4.3 times control, respectively. The data are consistent with extravascular albumin distributing into two pools that equilibrate with plasma at different rates. Papaverine and IVP affect the faster pool, whereas bradykinin affects both pools. PMID- 3337265 TI - Ion fluxes during tetanic stimulation in isolated perfused rat hindlimb. AB - The present study examined the relationships between changes in intra- and extracellular concentrations of strong ions, the appearance of nonvolatile acid (NVA) in venous perfusate, and skeletal muscle fatigue during intense electrical stimulation. A one-pass system was used to perfuse an isolated rat hindlimb during 5 min of intermittent tetanic contractions. Initial isometric tensions averaged 2.85 kg/hindlimb and declined by 45% during 5 min. During stimulation, intracellular lactate concentration ([La-]i) increased by 2, 13, 15, and 21 meq/l of intracellular fluid in the soleus, plantaris, and red and white gastrocnemius. This was associated with a proportionate decrease in intracellular K+ ([K+]i) and Mg2+([Mg2+]i) concentrations and increased intracellular Na+ ([Na+]i) and Cl-([Cl ]i) concentrations. A stoichiometrically equivalent uptake of Na+ and Cl- from the perfusate peaked at 8.5 mu eq.min-1.g-1 at the end of the 5th min. The increase in plasma [K+] during the last 4 min of stimulation was constant at 0.5 mu eq.min-1.g-1. A significant reduction in intracellular strong ion difference of all muscles contributed directly to an increase in [H+] during stimulation. After the 1st min of stimulation the rate of appearance of NVA in venous perfusate exceeded that of the increase in venous plasma [La-] by 12-fold; this decreased to 2.7-fold at the end of 5 min. La- release and NVA appearance in venous perfusate was maximal at 3.1 and 9.7 mu eq.min-1.g wet wt-1 during the 4th min of stimulation. It is concluded that the changes in the intracellular concentrations of strong ions during intense contractile activity are the primary factors contributing to skeletal muscle fatigue. PMID- 3337264 TI - Interaction of carotid chemoreceptor and baroreceptor reflexes in anesthetized dogs. AB - Interaction between baroreceptors and chemoreceptors during simultaneous activation of the reflexes was studied in eight pentobarbital sodium-anesthetized vagotomized dogs. The carotid sinus reflexogenic area was isolated and perfused at controlled carotid sinus pressure (CSP), PO2, and PCO2. Random combinations of CSP, PO2, and PCO2 were delivered to the carotid sinus. Results were analyzed by multiple linear regression. For the arterial pressure response, increasing CO2 resulted in an upward shift of the baroreceptor reflex response curve and an increased slope of the linear portion of the curve. The heart rate-CSP curve was also shifted upward by CO2, with the effect being greatest at high levels of CSP. The respiratory frequency-CO2 relationship had an increased slope and was shifted upward when CSP was decreased. The responses of tidal volume and ventilation (VE) depended on all three inputs. At any level of PO2, decreasing CSP resulted in a parallel shift of the VE-CO2 relationship. The results indicate that there is a significant interaction between chemoreceptor and baroreceptor reflex sensitivities. PMID- 3337266 TI - Electrogenic ATP-dependent Cl- transport by plasma membrane vesicles from Aplysia intestine. AB - A Cl--stimulated adenosinetriphosphatase (ATPase) activity and an ATP-dependent Cl- transport process were found in Aplysia enterocyte plasma membranes. In an attempt to further elucidate this transport process plasma membrane vesicles from Aplysia enterocytes were prepared utilizing differential centrifugation and sucrose density gradient techniques. Electrogenicity of the ATP-dependent Cl- transport was confirmed in three ways. First, an inwardly directed valinomycin induced K+ diffusion potential, making the vesicle interior electrically positive, enhanced ATP-driven Cl- uptake compared with vesicles lacking the ionophore. Second, ATP plus Cl- increased intravesicular negativity measured by lipophilic triphenylmethylphosphonium distribution across the vesicular membrane. Third, both vanadate and thiocyanate inhibited the ATP plus Cl--dependent intravesicular negativity. These results are consistent with the hypothesis that the active electrogenic Cl- transport mechanism in Aplysia intestine could be a Cl--stimulated ATPase found in the enterocyte plasma membrane. PMID- 3337267 TI - Calcium metabolism in the rat: a temporal self-organized model. AB - Based on consideration of rat plasma Ca and 45Ca concentrations, we analyze the circadian behavior of Ca metabolism of the rat as the temporal expression of a self-organized system. We present a self-oscillatory model M for rat Ca metabolism based on a compartmental formalism, which includes a second-order autocatalytic process. M describes the entire mass of Ca as made up of eight compartments and predicts a distinction between 1) the amount of Ca deposited in zones of rapid bone growth and reutilized during bone maturation and 2) the amount of Ca in mature bone subdivided into four compartments. Two of these compartments, largely self-oscillating, may represent Ca-P associations at bone liquid/solid interface and are subject to osteoblast-osteocyte control. The other two compartments can be thought of as made up of a large expanding pool of hydroxyapatite (HA) crystals, which are largely unavailable as such, and a small pool or more available HA crystals. Bone Ca influx and rhythmic efflux play a major role in the regulation of Ca in extracellular fluid but must be dissociated from bone accretion and resorption. Application to Ca deficiency was analyzed. Conceptual consequences of the connection of Ca metabolism to a self-regulated system are discussed. PMID- 3337268 TI - Effect of continuous infusions of CCK-8 on food intake and body and pancreatic weights in rats. AB - The ability of cholecystokinin (CCK) to act as a long-term satiety factor was assessed by its continuous infusion into the jugular veins of rats. Animals receiving a low dose of cholecystokinin octapeptide (CCK-8) (0.6 microgram CCK 8.kg body wt-1.h-1) did not show any significant differences in body weight changes or in food consumption from rats receiving saline and a group of unoperated controls over the 7-day infusion period. A 19.3-fold greater dose of CCK-8 (11.6 micrograms.kg body wt-1.h-1) did cause a significant decline in food consumption for the first 4 days compared with saline-infused rats (P less than 0.05) and unoperated controls (P less than 0.01). Rats receiving a high dose of CCK gained weight at a slower rate than rats receiving saline, but this effect lasted only 2 days and was not significant. Pancreatic growth was used as an indirect measure of elevated CCK levels in these animals. The infusion of 0.6 microgram CCK-8.kg body wt-1.h-1 did not lead to sufficiently elevated peptide levels to promote pancreatic growth. In contrast, those rats receiving a high dose of CCK-8 had significantly greater pancreatic weights (P less than 0.01) compared with saline-treated rats and unoperated controls. These results indicate that CCK-8, when administered continuously and in a large enough dose, can suppress food intake in rats for a period of several days before losing its effectiveness. PMID- 3337270 TI - Protein and lipid utilization during long-term fasting in emperor penguins. AB - The body mass of male emperor penguins is approximately 38 kg at the beginning of the 4-mo winter fast connected with breeding, and it is an estimated approximately 18 kg in leanest birds at time of spontaneous refeeding. For a 38- to 18-kg range, we investigated the changes in the rate of body mass loss, body composition, and plasma concentrations of uric acid and urea. After the first few days (phase I) a steady state (phase II) was reached in the proportions of the energy derived from proteins and lipids with proteins accounting for a constant 4%, and the remaining 96% being from lipids. The same proportions were maintained until body mass had decreased to 24 kg. Below this value the proportion of energy derived from proteins increased progressively (phase III), being 14 times higher at 18 kg than during phase II. Rate of body mass loss and plasma uric acid and urea concentrations closely reflected the changes in protein utilization: being at a low and steady value throughout phase II and increasing during phase III. Emperor penguins also fast during the spring, but for periods of only 2-3 wk. We found a 2.5 times higher value for rate of body mass loss, uric acid, and urea during spring phase II, suggesting lower effectiveness in protein sparing at that time. It may be attributed to the lower initial lipid reserves of spring birds. Would these findings be generalized to the wide variety of birds and mammals that spontaneously fast under natural conditions?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337269 TI - Refeeding hypertension in dietary obesity. AB - A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state (125 +/- 8 vs. 121 +/- 4 mmHg in chow-fed controls) or mean arterial pressure under urethan anesthesia (71 +/- 4 vs. 63 +/- 3 mmHg). In contrast, mild hypertension developed in intermittantly fasted obese animals (a 21-mmHg increase in systolic blood pressure measured in the conscious state and a 16-mmHg increase in mean arterial pressure under anesthesia relative to chow-fed controls). The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure (12 +/- 2 mmHg at 2 days) accompanied the onset of supplemented fasting and was maintained thereafter (2.7 +/- 2.6 mmHg further decrease during the latter half of the fast). With refeeding, blood pressure rose precipitously (13 +/- 3 mmHg in the 1st 2 days), despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period (5.2 +/- 2.8 mmHg). After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337271 TI - Effect of arterial pressure on drinking and urinary responses to angiotensin II. AB - To investigate the relationship between angiotensin II (ANG II) and mean arterial pressure (MAP) in the control of drinking in rats, we infused ANG II intravenously at constant rates (either 50 or 100 ng.kg-1.min-1 for 90 min) and varied MAP by intravenous injections of diazoxide (5-20 mg/kg). Rats were pretreated with captopril to block the endogenous synthesis of ANG II. When given alone, low and high doses of ANG II increased MAP approximately 30 and 50 mmHg, respectively. The low but not the high dose significantly increased water intake above control levels. Both doses caused such a large diuresis and natriuresis that the net effect was fluid loss. Reducing MAP toward normal greatly increased the drinking response to the high but not the low dose of ANG II and reduced the urinary solute and water loss to both doses. These results support the hypothesis that water intake and net fluid gain are inhibited when MAP is above normal. When MAP was reduced below normal in rats given constant infusions of ANG II the amount of water drunk and net fluid gain was proportional to the dose of ANG II but not the dose of diazoxide, the degree of hypotension, or urinary losses. This is consistent with previous reports that ANG II is essential for the drinking response to hypotension. Furthermore, it demonstrates that ANG II is not merely permissive but probably the signal controlling water intake when arterial pressure is reduced below normal. PMID- 3337272 TI - Verapamil blockade of pressor and uterine responses to AVP-OT analogue, oxypressin. AB - The effects of the calcium channel blocker verapamil on simultaneously recorded uterine and pressor responses to the equipotent (in eliciting these responses) oxytocin-vasopressin analogue, oxypressin, were studied in urethan-anesthetized and pentolinium- and indomethacin-treated rats during injections and infusions of this analogue. Doses of verapamil that almost completely blocked the pressor response to infused oxypressin had no effect on a pressor response to injected oxypressin of equal magnitude. Larger doses of verapamil blocked the pressor response to injected oxypressin somewhat. Uterine responses were only marginally affected by these doses of verapamil, and there was no significant difference between infusion and injection or between estrus and diestrus. PMID- 3337274 TI - Effect of clonidine on the thermic effect of feeding in humans. AB - Previous studies in humans attempting to assess the role of the sympathetic nervous system (SNS) in the thermic effect of feeding (TEF) have investigated the effect of oral or intravenous propranolol on TEF. This approach is potentially limited, however, because of the direct effects of propranolol on catecholamine and thyroid metabolism. In the present study we chose instead to evaluate the effect of clonidine, a centrally acting alpha 2-adrenergic receptor agonist that inhibits SNS outflow, on TEF and SNS activity as reflected by both plasma catecholamines and norepinephrine (NE) kinetics. The TEF and SNS response to an 800-kcal high-carbohydrate liquid meal (85% carbohydrate, 15% protein) was studied in eight healthy male subjects (27 +/- 6 yr) on two separate occasions with the subjects wearing either a clonidine or placebo skin patch for 48 h prior to study. Clonidine significantly suppressed base-line plasma NE concentration ( 46%, P less than 0.01) and NE appearance rate (-47%, P = 0.01) compared with placebo, whereas there was no significant effect on epinephrine concentrations, NE clearance rate, or base-line energy expenditure. The expected increments in plasma NE and NE appearance after a meal were also reduced by 54% (P less than 0.05) and 70% (P less than 0.01) of placebo values, respectively, after clonidine. Associated with this reduced SNS response to the meal was a blunting of the expected TEF by 33% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337273 TI - Effects of a 1-wk spaceflight on morphological and mechanical properties of growing bone. AB - The morphological and mechanical responses of tibia and humerus were assessed in growing male rats after a 1-wk spaceflight aboard NASA Spacelab 3. In contrast to flights of longer duration, changes in middiaphysial cross-sectional morphology were minimal. Inhibition of longitudinal growth was not found in the tibia but was apparent in the humerus. The normal age-related increase in tibial middiaphysial density was not observed in the flight animals. Three-point bending tests indicated that a 1-wk spaceflight impeded the maturation of bone strength and stiffness, with the effects more pronounced in the tibia than in the humerus. Material property alterations in bone thus overshadowed morphological factors in determining the bone's mechanical response. It is likely that deprivation of normal weight-bearing loads was a major factor contributing to the observed changes, but endocrine and other local factors must also be considered. PMID- 3337275 TI - Psychiatrist-executive management styles: nature or nurture? AB - The authors studied the management styles of the 11 directors of psychiatry in municipal general hospitals in New York City. The Lead-Self Scale and the Lead Other Scale were used. The directors' Lead-Self Scale scores were compared with those of 11 psychiatric residents. Results show that the directors had a high task/high relationship primary style and a high relationship/low task secondary style. Psychiatric residents revealed a less differentiated pattern of self perceived management style. The authors speculate about the effects of experience, training, role models, and personality traits on management styles and suggest areas for further research. PMID- 3337276 TI - Self-care capacity and anticholinergic drug levels in nursing home patients. AB - The serum anticholinergic levels of 22 demented nursing home patients were related to their cognition and capacity for self-care. The patients with high anticholinergic levels had greater impairment in self-care capacity than patients with low levels. PMID- 3337277 TI - The homeless mentally ill in Tucson: implications of early findings. AB - Homeless persons who received emergency psychiatric screening in a public general hospital exhibited patterns of gross geographic mobility. They did not uniformly avail themselves of community services, such as soup kitchens, and there were marked sex differences within the sample. PMID- 3337278 TI - Rapid cycling bipolar II illness in three closely related individuals. AB - The author describes three related women with rapid cycling bipolar II disorder. Their cycles of approximately 55 days usually included 3-7 days of hypomania, followed by 5 weeks of mild to moderate depression and 2 weeks of severe depression. PMID- 3337279 TI - The seeking and liking potentials of alprazolam. PMID- 3337280 TI - Administration of ECT 4 years after aortic aneurysm dissection. PMID- 3337281 TI - Mania associated with procainamide. PMID- 3337282 TI - Potential spread of AIDS to fundamentalist spouses. PMID- 3337284 TI - Defining late luteal phase dysphoric disorder. PMID- 3337285 TI - Redefining psychiatry. PMID- 3337283 TI - More on the psychodynamic formulation. PMID- 3337286 TI - Spontaneous remission of MAOI-induced anorgasmia. PMID- 3337287 TI - Psychodynamic therapy with borderline patients. PMID- 3337288 TI - High users of outpatient mental health services, I: Definition and characteristics. AB - Mental health coverage generally limits benefits for high use, which is assumed to be discretionary. The authors present data from the National Medical Care Utilization and Expenditure Survey. Of the individuals who made mental health outpatient visits in 1980, 9.4% made 25 or more visits and accounted for 50% of mental health visits and expenditures. These high users were compared with low users and with high users of other health care. One-third of the mental health high users were highly disabled and had multiple medical disorders. The authors point out the heterogeneity of this population and suggest that psychiatric benefits be differentiated according to patients' needs and services offered. PMID- 3337289 TI - High users of outpatient mental health services, II: Implications for practice and policy. AB - Four assumptions underlie the stereotyped view of use of outpatient mental health services: 1) all use is alike, 2) any use leads to high use, 3) all high use is discretionary, and 4) insurance encourages excessive use. The authors refute the first three assumptions and suggest that different types of treatment episodes vary in their responsiveness to price. Diagnosis appears to be a poor indicator of inpatient needs; some coverage limits outpatient benefits according to type of treatment. The authors favor a combination of pricing strategies, as well as case management and clinical review for high users, which would not impede initial treatment but would limit excessive use of mental health services. PMID- 3337290 TI - Validity of subtyping psychotic depression: examination of phenomenology and demographic characteristics. AB - The authors examine the validity of subtyping psychotic depression by comparing 111 patients with schizoaffective, unipolar, and bipolar psychotic depression on demographic characteristics and symptoms at index episode. Diagnoses were made by using Research Diagnostic Criteria (RDC). The three groups were indistinguishable in sex, race, and age at onset. Schizoaffective patients had more "schizophrenic" symptoms but were not different in depressive delusions, other psychotic symptoms, or affective symptoms. However, bipolar patients scored significantly higher than nonbipolar patients on hypomania. There is little support in these data for the schizoaffective versus nonschizoaffective distinction. Further tests are needed, including tests of response to treatment and biological markers. PMID- 3337291 TI - Sex differences in recurrent depression: are there any that are significant? AB - The authors report on sex differences in a group of 230 patients with recurrent depression. Male and female patients were similar in clinical characteristics and baseline measures of severity. Some sex differences in depressive symptoms were apparent, especially as reflected by self-report instruments. The women reported more appetite and weight increase, more somatization, and expressed anger and hostility. The men demonstrated a more rapid response to treatment. Various interpretations of these findings are discussed. PMID- 3337292 TI - Influences of time, ethnicity, and attachment on depression in Southeast Asian refugees. AB - The author reports on a study investigating the question of whether certain phases of resettlement are accompanied by an elevated risk for depression in Southeast Asian refugees in Canada. In general, the longer the Southeast Asian refugees remained in Canada, the better their mental health. However, unmarried or otherwise unattached Laotians and Vietnamese refugees experienced high levels of depression 10-12 months after arrival. Two years after the initial investigation, this group, disadvantaged by a lack of social resources, continued to be more depressed than other refugees. PMID- 3337293 TI - A family study of the subtypes of schizophrenia. AB - The authors conducted a blind family study based on probands diagnosed as schizophrenic by DSM-III and subtyped by four diagnostic systems. The pattern of psychopathology in relatives did not differ as a function of the probands' subtype diagnosis. Relatives of paranoid and nonparanoid schizophrenic probands had similar risks for schizophrenia and affective illness. Resemblance in subtype diagnosis between probands and their affected relatives did not exceed chance expectation. The etiologic role of familial factors appears to be similar in each of the traditional subtypes of schizophrenia. No evidence was found for familial factors specific for individual subtypes. PMID- 3337294 TI - Resilient adolescents whose parents have serious affective and other psychiatric disorders: importance of self-understanding and relationships. AB - Eighteen young men and women whose parents had major affective disorders, often in combination with other serious psychiatric disorders, were selected from a larger sample on the basis of their good behavioral functioning as adolescents at initial assessment. When they were reassessed an average of 2 1/2 years later, 15 of the 18 were still functioning well. Considerable self-understanding, a deep commitment to relationships, and the ability to think and act separately from their parents characterized these young people. Many of them were taking care of their ill parents. The implications of these findings for preventive and clinical intervention are discussed. PMID- 3337295 TI - Pedigrees, functioning, and psychopathology in families of school phobic children. AB - Family pedigrees of six children with severe school phobia compared with those of a matched group of families of five children with psychiatric disorders showed a clustering of affective and anxiety disorders. Blind and independent family histories and structured interviews of parents and siblings demonstrated higher rates of depressive and anxiety disorders in first-degree relatives of children with school phobia. Parents of children with school phobia described more disturbance in family functioning on the Family Assessment Measure than did parents in the comparison group in the areas of role performance, communication, affective expression, and control. PMID- 3337297 TI - Response of psychotic and nonpsychotic depression to phenelzine. AB - The authors studied 52 depressed inpatients to examine treatment response to phenelzine, a monoamine oxidase (MAO) inhibitor. All patients were classified into one of three RDC categories (definitely psychotic, probably psychotic, and nonpsychotic). For the entire sample, the mean platelet MAO inhibition level achieved with phenelzine was greater than 80%. Response to treatment was determined by independent clinical assessment and by the change in rating scores from baseline; 68% of the nonpsychotic, 43% of the probably psychotic, and 21% of the definitely psychotic patients were classified as responders. This differential response rate is similar to that reported in the literature for tricyclic antidepressants. PMID- 3337298 TI - Smoking and risk of gallstone disease. PMID- 3337296 TI - Relationship of chronic pelvic pain to psychiatric diagnoses and childhood sexual abuse. AB - Structured psychiatric and sexual abuse interviews were administered to 25 women with chronic pelvic pain and a comparison group of 30 women with specific gynecological conditions. All 55 patients underwent diagnostic laparoscopy, and the results of the fiberoptic pelvic examination were objectively classified by the study gynecologist, who was blind to the psychiatric diagnoses. The patients with chronic pelvic pain showed a significantly higher prevalence of major depression, substance abuse, adult sexual dysfunction, somatization, and history of childhood and adult sexual abuse than the comparison group. There were no significant differences between the groups in severity or type of pelvic pathology. PMID- 3337299 TI - Childhood acute respiratory tract infections deserve our attention. PMID- 3337300 TI - Impact and costs of varicella prevention in a university hospital. AB - Information regarding all patient and staff exposures to varicella-zoster virus (VZV) was prospectively accumulated from 1/1/86 to 12/31/86 at North Carolina Memorial Hospital. During this period of time 37 sources of exposure to VZV were reported: 10 outside and 27 within the hospital. Index cases for nosocomial exposure included: 12 patients with zoster, 9 patients with varicella, two staff with varicella, three visitors with varicella, and one staff with zoster. One hundred and twenty patients received nosocomial exposures; 28 had no history of VZV infection (23 per cent), of whom 11 were serosusceptible (39 per cent). Sources of nosocomial patient exposure included: other patients (85 per cent), staff (14 per cent), and a single visitor (1 per cent). More than 300 employees received nosocomial exposure; 158 had no history of VZV infection, of whom 49 were serosusceptible (31 per cent). Only a single employee and no patients developed clinical varicella as a result of nosocomial exposure. Costs associated with VZV control during 1986 totaled $55,934: $39,658 for work furloughs, $9,800 for serologies, $4,293 for patient isolation, $155 for varicella-zoster immune globulin, and $2,028 for infection control personnel time. These costs should be considered as part of any benefit-cost analysis of varicella immunization of health care personnel. PMID- 3337301 TI - Transmission of hepatitis B virus from adopted Asian children to their American families. AB - In 1985, 6,991 Asian children were adopted by Americans. To estimate the risk that such children may transmit hepatitis B virus to their adoptive families, we conducted a cumulative-incidence follow-up study in the State of Washington. We examined the association between having adopted a hepatitis B surface antigen (HBsAg)-seropositive Asian child and serologic evidence of past or present hepatitis B virus infection in adoptive family members. Seven (9 per cent) of 77 family members exposed to an HBsAg-seropositive child had evidence of past or present infection compared with four (2 per cent) of 232 nonexposed (relative risk = 5.3; 90% confidence limits [CL] = 2.0-13.9). The risk was higher for those with prolonged exposure and was entirely restricted to parents. PMID- 3337303 TI - Correcting spontaneous abortion rates for the presence of induced abortion. AB - This paper introduces a method for correcting spontaneous abortion rates by taking into consideration the fact that a number of spontaneous abortions are "prevented" by induced abortions. This correction may be important in settings of high induced abortion incidence. The method is then applied to the data of the Italian region of Lombardy. The results obtained are compared to those obtained with previous correction methods, and it is concluded that the present method is useful and appropriate when data on induced and spontaneous abortions are available by gestational age. PMID- 3337302 TI - Lower respiratory tract illness in the first two years of life: epidemiologic patterns and costs in a suburban pediatric practice. AB - The epidemiologic patterns and the economic impact of acute lower respiratory tract illness (LRTI) in children under age two were studied using data collected from November 1, 1971-August 30, 1975 in a suburban pediatric practice in Monroe County, New York. LRTI was responsible for 23 illness episodes per 100 child years among children in their first two years of life. This indicates that a cohort of 100 children might be anticipated to have 46 LRTI episodes from birth until their second birthday. The majority of episodes correlated with the presence of four viruses in the community, most commonly respiratory syncytial virus. The minimal, estimated direct cost of LRTI in the first two years of life based on 1984 cost data was equivalent to $35.14 for every child and was comprised of hospitalization cost ($19.68) and ambulatory care cost ($15.46). Hospitalization costs attributable to LRTI comprised at least 2.5 per cent of all hospitalization costs in this age group. Immunization against the four most common respiratory viruses, at a reasonable cost per child immunized, would appear to be cost beneficial. PMID- 3337305 TI - Problems associated with collecting drinking water quality data for community studies: a case example, Fresno County, California. AB - This paper discusses methodology in developing exposure data for the water supply contaminant dibromochloropropane (DBCP) in Fresno County, California. There are 532 drinking water systems (49 large and 483 small) within Fresno County plus 14,000 private wells. We determined the number of wells per system, the output per well, and the population served by each system. The task of deriving water quality estimates for each census tract was complicated by the fact that a single census tract can be served by more than one system; each system usually has more than one well; and a single well can have several episodes of testing for various contaminants. We calculated a series of weighted averages for concentrations of DBCP, arsenic, and nitrates for each census tract, using water production figures for each well as the weighting factor. Water quality data were derived from a total of 14,861 laboratory reports, although the majority did not report on all contaminants. Mean DBCP levels ranged from 0.0041 ppb to 5.7543 ppb among the census tracts. We found no correlation between DBCP levels per census tract compared to either arsenic or nitrates. We believe that we made as complete an exposure assessment as practically feasible. PMID- 3337304 TI - An epidemiologic investigation of the relationship between DBCP contamination in drinking water and birth rates in Fresno County, California. AB - This report describes an epidemiologic investigation of the relationship between DBCP (dibromochloropropane) contamination in drinking water and birth rates between 1978 and 1982 in Fresno County, California. Census tracts in the county were categorized according to DBCP level in their drinking water. Standardized birth ratios and relative birth ratios (adjusted for age, race, per cent Hispanic, and parity) were calculated for these census tracts. No relation between birth ratios and DBCP contamination in drinking water was found. PMID- 3337306 TI - Minorities and AIDS: knowledge, attitudes, and misconceptions among black and Latino adolescents. AB - White adolescents in San Francisco high schools were more knowledgeable than Black adolescents about the cause, transmission, and prevention of AIDS (acquired immunodeficiency syndrome), and Black adolescents were more knowledgeable than their Latino peers. Black and Latino adolescents were approximately twice as likely as White adolescents to have misconceptions about the casual transmission of AIDS. Less knowledge about AIDS and prevalent misconceptions were associated with greater levels of perceived risk of contracting AIDS. PMID- 3337307 TI - Correlates of smokeless tobacco use in a male adolescent population. AB - This paper identifies the correlates of smokeless tobacco use in a sample of 1,030 males representative of 7th through 12th grade students of Dane County (Madison), Wisconsin. Variables independently associated with frequent use of smokeless tobacco were: being White; living in other than a two-parent home; performing poorly in school; smoking cigarettes; consuming beer, wine, or hard liquor; and deviant/delinquent behavior. Participation in team sports was associated with some "experimentation" with smokeless products. PMID- 3337308 TI - Racial trends in syphilis among men with same-sex partners in Atlanta, Georgia. AB - Early syphilis cases attributable to homosexual transmission declined in DeKalb County, Georgia, from 191 in 1981 to 97 in 1985. This decline occurred only among White men with same sex partners (SSP); early syphilis among Black men with same sex partners has risen. This pattern is consistent with the hypothesis that changes in sexual behavior instituted by White men at risk of acquiring HTLV III/LAV infection may have resulted in decreased incidence of early syphilis among those men. PMID- 3337309 TI - The effect of sunglasses on ocular exposure to ultraviolet radiation. AB - Thirty-two pairs of inexpensive sunglasses were examined for their effectiveness in preventing ultraviolet radiation (UVR) from reaching the eyes. The transmission of UVB (290-310 nm) by all of the sunglass lenses was less than 2 per cent. However, in measurements performed with mannikins wearing the sunglasses, up to 14.1 per cent of the incident UVR passed through to the eyes. When the sunglasses were moved 6 mm from the forehead, the per cent reaching the eyes ranged from 3.7 to 44.8 per cent. Although sunglasses are somewhat more effective than untinted prescription eyewear in attenuating ocular exposure, the amount of attenuation is highly variable and depends mainly on their size, shape, and wearing position. PMID- 3337311 TI - Marital status and the risk of suicide. AB - No recent United States study has previously calculated national suicide rates by marital status for specific age, race, and sex categories in order to better identify high-risk groups for suicide. We used national vital statistics and census data to calculate marital-status-specific rates. Results show that for each marital status group, by age and sex, married persons have the lowest suicide rates and young widowed males have exceptionally high rates. PMID- 3337310 TI - Secular trends of obesity in early life: the Bogalusa Heart Study. AB - Secular changes in height and weight measurements were examined in five- to 14 year-olds from 1973 to 1984. The age-sex specific 85th percentile was used to classify persons as overweight (based on ponderal index; kg/m3). Secular increases in weight (2.5 kg), and ponderosity (0.5-0.7 kg/m3) were found. Gains in ponderosity over the 11-year period were greater at the 75th percentile than at the 25th percentile, and the prevalence of overweight increased from 15 per cent to 24 per cent. PMID- 3337312 TI - Sexual behavior and risks of HIV infection. PMID- 3337313 TI - Smaller packs of cigarettes. PMID- 3337314 TI - Mental disorder and social policy. PMID- 3337315 TI - Medical treatment of homeless hypertensives. PMID- 3337316 TI - Lead-induced neuropathy. PMID- 3337317 TI - Place of birth: a woman's choice. PMID- 3337318 TI - New laws ameliorate OB crisis in Missouri. PMID- 3337319 TI - C-section rate related to payment source. PMID- 3337320 TI - Wading pools: a source of drowning. PMID- 3337321 TI - On food assistance programs and nutrition education. PMID- 3337322 TI - Marriage to a smoker and lung cancer risk. PMID- 3337323 TI - Purple burps and the filtration of drinking water supplies. PMID- 3337324 TI - Uniform minimum data sets: in search of demographic comparability. PMID- 3337325 TI - Problems with surveillance methods for alcoholism: differences in coding systems among federal, state, and private agencies. AB - Social indicator systems can serve as a social accounting method to guide public policy on alcoholism, utilizing data which are routinely collected at public expense. An attempt to develop an alcoholism social indicator system for Minnesota demonstrated many differences in the coding schemes used by various state agencies and institutions. These findings have relevance to other social indicator systems being developed to assess public policies regarding the people's health. PMID- 3337326 TI - Patterns of mental health utilization over time in a fee-for-service population. AB - This paper examines the multi-year patterns of ambulatory mental health care in a population of individuals continuously eligible to receive care in a fee-for service setting. Among the 14,000 individuals eligible for all three years, 14 per cent used outpatient mental health services during at least one of the three years. Almost 70 per cent of the individuals with some use in 1980 used services during 1981 or 1982. The heaviest use of outpatient mental health and other physician services is among the persons using services in all three years. Our data are compared with three years of data reported by Kessler in an HMO (health maintenance organization) setting. The probability that a non-user becomes a user in roughly the same in the fee-for-service and HMO populations, but the probability of continuing use in the next year is much less in the HMO. This finding, that the "HMO effect" on mental health care is primarily on the visits per user rather than on the number of users, is consistent with other research. PMID- 3337327 TI - The quality of care is related to death rates: hospital inpatient management of infants with acute gastroenteritis in Jamaica. AB - The quality of care of random samples of about 40 infants admitted with acute gastroenteritis to each of five hospitals in Jamaica was assessed. Low levels of adherence to consensus care criteria appeared to be correlated with high levels of hospital-specific severity standardized mortality ratios X100 (SSMRs); poor adherence, SSMR 127-230; intermediate adherence, SSMR 95; good adherence, SSMR 14. The main deficiencies in care at certain hospitals were: non-weighing of infants, incomplete physical examination, inadequate estimation of fluid requirements, and irregular recording of fluid intake. To improve the effective care of infants with gastroenteritis, a quality assurance program is required. PMID- 3337328 TI - Associations between alcoholic beverage consumption and hospitalization, 1983 National Health Interview Survey. AB - Data collected in the Alcohol Supplement and core 1983 National Health Interview Survey were used to examine associations between alcoholic beverage consumption and hospitalization. Hospitalizations in acute care facilities (excluding hospitalizations for delivery) in the past 12 months, were treated as dichotomous (any vs none) and examined in relation to alcohol consumption in a logistic regression model adjusting for age, race, income, and smoking. Findings are based on 17,600 individuals meeting inclusion criteria. The adjusted odds ratio of having one or more hospitalization for current drinkers relative to life-long abstainers in females was 0.67 (95 per cent confidence interval 0.57-0.79) and in males was 0.74 (0.57-0.96). U-shaped relationships between level of current alcohol intake and odds of hospitalization were found. While some causes of hospitalization are clearly increased among drinkers, the overall acute care hospitalization experience of moderate drinkers appears to be favorable. PMID- 3337329 TI - State-level pharmaceutical assistance programs for the elderly: a national survey. AB - In order to put Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) Program in a national context, a nationwide mail survey and telephone follow-up to each of the 58 State Unit Directors on Aging in the United States and its territories identified 10 programs. The results reported in this article are specific to the seven state-level pharmaceutical assistance programs which were in operation during the fiscal year 1984-85. In general, the programs varied on select program characteristics and on their efforts to address major policy issues. Data from the non-program states indicated support, legislative efforts, and a high interest in fiscal concerns. The findings reflect a lack of program uniformity and have implications for program development and implementation. Suggestions on how to identify the "optimum" or best combination of program and policy options are discussed. PMID- 3337330 TI - The epidemiology of life and death: a critical commentary. PMID- 3337331 TI - The 1989 revisions of the US Standard Certificates of Live Birth and Death and the US Standard Report of Fetal Death. AB - The US Standard Certificates and Reports are models used by state vital statistics offices to develop documents for the collection of data about vital events. The 1989 revisions incorporate some major modifications to previous versions. Both the Standard Certificate of Live Birth and the Standard Report of Fetal Death utilize a checkbox format to elicit information on medical and other risk factors affecting the pregnancy, complications of labor and/or delivery, obstetric procedures, method of delivery, congenital anomalies, and abnormal conditions of the newborn. Revisions to the Standard Certificate of Death include modifications to the medical certification section and the addition of decedent's educational attainment. Items requesting information about Hispanic origin are added to all of these documents. The rationale behind these changes and their intended use are discussed. PMID- 3337332 TI - Tobacco advertisements in physicians' offices: a pilot study of physician attitudes. AB - A pilot study evaluated the feasibility of a campaign to eliminate magazines advertising cigarettes from doctors' office waiting rooms. Only six of 51 waiting rooms visited did not contain cigarette ads. Only 25 per cent of physicians interviewed would participate in a subscription-cancellation campaign; they expressed doubt that this would influence patients' smoking behavior. This suggests that such a campaign will fail unless it is possible to change physicians' beliefs in its effectiveness. PMID- 3337333 TI - Smoking prevalence in a cohort of adolescents, including absentees, dropouts, and transfers. AB - This study reports daily smoking rates among older adolescents obtained by a unique follow-up of a cohort originally identified in the seventh grade. Those no longer in their original school districts were located and interviewed by telephone. Smoking rates among dropouts exceeded 70 per cent in all age-sex groups. Smoking rates among transfers were as high as those among absentees. Including these subgroups raised smoking prevalence rates among older adolescents substantially. PMID- 3337334 TI - Suicides in Alaska: firearms and alcohol. AB - A manual review of death certificates and autopsy records identified 195 suicides in Alaska during 1983-84. Native males, 20-24 years old, had the highest rate of suicide (257 per 100,000 person-years). Gunshot wounds caused 76 per cent of all suicide deaths; 79 per cent of Native and 48 per cent of White suicides had detectable levels of blood alcohol. Suicide by firearms was weakly associated with blood alcohol levels above 100 mg/dl (odds ratio 1.3, 95 per cent confidence interval 1.11-1.47). PMID- 3337335 TI - Fecundity and infertility in the United States. PMID- 3337336 TI - Prognostically favorable "mitotically active" smooth-muscle tumors of the uterus. A clinicopathologic study of ten cases. AB - We evaluated the clinicopathologic features of 22 smooth-muscle tumors of the uterine corpus that had at least five mitoses per 10 high-power fields (HPF) in the most active areas. Ten women were alive and well without tumor recurrence 15 months to 11 years after diagnosis (median, 6 years); these patients were referred to as the "clinically benign" group. The other 12 women had "clinically malignant" disease: 9 died of recurrent or metastatic tumor 3 months to 4.5 years after diagnosis (median, 16 months), and 3 are alive with disease 4-12 months after diagnosis. Significant clinical and pathologic differences were observed between patients in the "benign" and "malignant" groups. We found that mitotic activity in the range of 5 to 15 mitoses per 10 HPF was not a reliable predictor of aggressive behavior in tumors that lacked marked cytologic atypia and that by all other clinical and pathologic criteria were leiomyomas. An unfavorable prognosis among the mitotically active neoplasms could be predicted by a constellation of clinicopathologic features, including postmenopausal status, a clinical or intraoperative impression of cancer by the surgeon, extension of tumor beyond the uterine corpus, size greater than 10 cm, marked cytologic atypia, invasive borders, necrosis, and mitotic counts exceeding 20 per 10 HPF. PMID- 3337339 TI - Histology of the anal canal. AB - The normal gross and microscopic morphology of the anal canal is described, including the more common variants. Constant problems in the literature are the confusing terminology and the relation of the histological zones to the so-called cloacal membrane. For this reason, the review includes remarks on the history, embryology, and nomenclature. PMID- 3337338 TI - Pulmonary blastoma with rhabdomyosarcomatous differentiation: an electron microscopic and immunohistochemical study. AB - Pulmonary blastoma is a rare lung tumor composed of epithelial and mesenchymal elements; the latter element may show various patterns of differentiation toward mature tissue, such as cartilage, smooth muscle, and bone. Rhabdomyoblastic differentiation in pulmonary blastoma is quite rare; only five such cases have been reported. We report two cases of pulmonary blastoma with rhabdomyoblastic differentiation documented for the first time by electron microscopy and immunohistochemistry including documentation for myoglobin, actin, vimentin and desmin. The diffuse and prominent rhabdomyoblastic differentiation in one case is most unusual. PMID- 3337337 TI - Prognostic implications of the tall cell variant of papillary thyroid carcinoma. AB - The tall cell variant (TCV) of papillary thyroid carcinoma, characterized by a population of tall columnar cells with a height at least twice the width, was analyzed in 12 patients and compared to tumors from 12 patients with the usual type of papillary thyroid carcinoma (UPTC) matched for age, sex, and date of diagnosis to determine if tall cell histology had prognostic significance. Patients with TCV had significantly higher incidences of extrathyroidal disease, recurrent disease, and metastases compared to patients with UPTC. TCV patients also died of their tumors more frequently than UPTC patients (3/12 versus 0/12). There was no significant difference in tumor size or in the incidence of cervical lymph node involvement between the patient groups. These results show that TCV of papillary thyroid carcinoma has a more aggressive clinical course and a worse prognosis than UPTC in patient groups with similar age and sex distribution, length of follow-up, and tumor size. PMID- 3337340 TI - Heterotopic brain tissue. PMID- 3337341 TI - Potentiation of neuromuscular blocking agents by calcium channel blockers in rats. AB - The effect of calcium channel blockers (Ca-antagonists) on the potency and reversibility of muscle relaxants (MR) was investigated in the in vitro phrenic nerve-hemidiaphragm and in vivo sciatic nerve-tibialis anterior preparation of rats. To increase the relevance of the experimental findings to the clinical situation, the [Ca++] and [Mg++] in vitro were the same as in the plasma of rats and humans and the stimulation parameters used in vitro and in vivo were similar to those that elicit voluntary movements of the muscles used. Both verapamil and nifedipine significantly decreased the I50 and I90 of d-tubocurarine (d-Tc), pancuronium, vecuronium, and atracurium in vitro and those of the first three MR in vivo (P less than 0.001). In vitro, the depression of the force of contraction of the diaphragm (P) caused by all the Ca-antagonist-MR combinations could be reversed only partially by washout, neostigmine, or 4-aminopyridine. In vivo, because of limitations imposed by their cardiovascular depressant effect, the muscles were exposed to lower concentrations of Ca-antagonists for shorter periods. Under these circumstances the decrease of P caused by all Ca-antagonist MR combinations recovered spontaneously close to control levels. This study indicates that acute administration of verapamil during anesthesia may increase MR potency, but it is unlikely that spontaneous recovery or reversibility of the residual neuromuscular (NM) block at the end of anesthesia will be significantly affected. However, long-term administration of Ca-antagonists may make difficult the reversal of the residual NM block. PMID- 3337342 TI - Cardiac electrophysiologic effects of fentanyl and combinations of fentanyl and neuromuscular relaxants in pentobarbital-anesthetized dogs. AB - The effects of fentanyl, both alone and in combination with pancuronium bromide or succinylcholine, on atrioventricular (AV) node and ventricular conduction times and refractory periods were studied. Twenty-four pentobarbital-anesthetized dogs were instrumented both with an intraaortic catheter to measure cardiac conduction times and, through a thoracotomy, with atrial and ventricular epicardial pacing electrodes to provide premature stimulation that would allow measurement of atrial and ventricular refractoriness. Fentanyl prolonged the RR interval in both low- (100 micrograms/kg) and high-dose (400 micrograms/kg) groups by 26 and 45%, respectively, and prolonged AV node conduction time by 28 and 25%, respectively. During atrial pacing at a rate sufficient to capture the atria, AV node conduction time lengthened in the low- and high-dose groups by 27 and 25%, respectively. Fentanyl also significantly lengthened AV node effective and functional refractory periods and ventricular effective refractory periods in both groups. Pancuronium (0.1 mg/kg) administered after fentanyl shortened RR intervals in the low- and high-dose groups by 14 and 22%, respectively, and shortened AV conduction times by 18 and 20%, respectively, but did not restore all values to baseline. Pancuronium significantly shortened AV node refractory periods in the low-dose but not the high-dose group. When administered after fentanyl, succinylcholine (2 mg/kg) significantly shortened the RR interval in the low- and high-dose groups by 14 and 12%, respectively. Succinylcholine shortened AV node conduction slightly but without significance and had no effect on cardiac refractoriness. His-Purkinje conduction remained unaffected by any drug intervention. These data demonstrate that fentanyl depresses cardiac conduction; subsequent administration of pancuronium and succinylcholine partially reverses this effect. PMID- 3337343 TI - The anesthetic contribution of magnesium sulfate and ritodrine hydrochloride in rats. AB - The anesthetic effects of the tocolytic agents, magnesium sulfate and ritodrine hydrochloride, were investigated by determining their effect on the minimal alveolar anesthetic concentration (MAC) of halothane in male and in pregnant and nonpregnant female rats. Magnesium and ritodrine were administered by continuous intravenous infusion to mechanically ventilated rats anesthetized with halothane. The tail-clamp technique was used to establish the MAC of halothane before and then again during the infusion of either magnesium or ritodrine. Ritodrine produced no change in halothane MAC. Increasing magnesium dosages and magnesium plasma levels were associated with nonlinear reductions in halothane MAC that were unrelated to sex or pregnancy. The alveolar halothane MAC concentration in pregnant rats (0.85 +/- 0.02) was not significantly different from the halothane MAC in nonpregnant female or male rats. At the highest plasma magnesium concentrations (15.8 +/- 1.57 mg/dl) achieved in the pregnant rats, the alveolar halothane MAC was 0.36 +/- 0.13, a 61.6% reduction in MAC. The anesthetic effects of magnesium were not attributable to cardiovascular, respiratory, or neuromuscular depression. Major decreases in blood pressure occurred only in the pregnant rats with the highest magnesium concentrations. PMID- 3337344 TI - Comparison of bupivacaine and alkalinized bupivacaine in brachial plexus anesthesia. AB - To define the effect of alkalinization of bupivacaine 0.5% in subclavian perivascular brachial plexus blockade, the time to onset, time to peak effect, and 6-hour regression of sensory and motor blockade were determined. Sixty physical status ASA I and II patients were randomly allocated to one of two groups and a double-blind design was used: group I (n = 30) received bupivacaine 0.5% (pH, 5.5) 3 mg/kg, while group II (n = 30) received alkalinized bupivacaine 0.5% (pH, 7.05-7.15) 3 mg/kg. Onset and regression of sensory blockade were determined by pinprick in the C4-T2 skin dermatomes, while motor blockade was assessed using a scheme of proximal to distal muscle group paralysis. Time to onset of sensory blockade (group I, 4.0 +/- 1.2 min; group II, 3.6 +/- 0.9 min) and time to peak sensory effect (group I, 17.7 +/- 1.8 min; group II, 16.3 +/- 1.8 min) did not differ significantly between the groups. Similarly, no difference in time to onset of motor blockade (group I, 6.9 +/- 1.7 min; group II, 6.3 +/- 1.5 min) or time to peak motor effect (group I, 18.1 +/- 1.9 min; group II, 15.1 +/- 1.9 min) was observed. Regression of postoperative sensory and motor blockade was similar in both groups. It is concluded that alkalinization of bupivacaine 0.5% solutions does not confer any added clinical advantage in subclavian perivascular brachial plexus blockade when compared with commercially available bupivacaine. PMID- 3337345 TI - Recovery scores do not correlate with postoperative hypoxemia in children. AB - The correlation between the degree of postanesthetic recovery (PAR) in children as measured by a modified Aldrete scoring system and oxygen saturation (SaO2) was studied. Eighty-one ASA PS I unpremedicated infants and children were studied. Oxygen saturation and PAR scores were recorded on arrival in the recovery room, then at 5-minute-intervals. Patients with SaO2 less than 95% were given supplemental oxygen. The proportion of children with SaO2 less than 95% and greater than or equal to 95% was not significantly different among patients with low PAR scores (less than or equal to 6) and those with high scores (7-10) in any age group. Similarly, the magnitude of SaO2 increase after oxygen supplementation did not seem to correlate with increasing wakefulness; i.e., higher PAR scores. It is concluded that children recovering from anesthesia can become hypoxemic in the recovery room. The degree of wakefulness as measured by a PAR score cannot be used to establish an end point for oxygen supplementation. Oxygen supplementation and/or SaO2 monitoring are recommended in all children recovering from anesthesia. PMID- 3337346 TI - Long-term bupivacaine infusion does not alter the acute seizure threshold to bupivacaine in rats. AB - Rats were given a continuous subcutaneous infusion of either bupivacaine (n = 18) or placebo (n = 17) for 4 days. On the 5th day the acute seizure threshold to intravenous bupivacaine was determined in both groups. Blood and brain concentrations of bupivacaine at the onset of seizures showed no difference between the two groups, whereas the seizure dose was decreased in the bupivacaine group. The tachyphylaxis observed when bupivacaine is used for a regional nerve blockade does not seem to evolve for the central nervous system effects. PMID- 3337347 TI - Neonatal neurobehavior after epidural anesthesia for cesarean section: a comparison of bupivacaine and chloroprocaine. AB - Reports of whether or not bupivacaine affects neonatal neurobehavior have been contradictory. The purpose of this study was to test the hypothesis that scores on the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) after epidural anesthesia with bupivacaine for cesarean section would not be different than those after chloroprocaine. Furthermore, if there were any effects, it was hypothesized that they would be related to cord blood levels of the drug. Fifty five healthy mother/infant pairs were studied. Clinical characteristics, pharmacologic data, and BNBAS scores were obtained and analyzed using statistical techniques that included t-tests, repeated measures analysis of variance, and stepwise multiple regression. The results indicate that infants in the bupivacaine group do significantly better than those in the chloroprocaine group in the orientation cluster of the BNBAS (F[1,49] = 22, P less than 0.001); this cluster reflects higher cortical functioning. Furthermore, there was improvement in the bupivacaine group in the regulation of state cluster with age, whereas there was no improvement in the chloroprocaine group (F[1,53] = 4.34, P less than 0.01). This study suggests that performance on the BNBAS after exposure to bupivacaine is better than that after exposure to chloroprocaine. PMID- 3337349 TI - Massive macroglossia and airway obstruction after cleft palate repair. PMID- 3337348 TI - Cimetidine does not affect plasma cholinesterase activity. AB - Blood samples were drawn from 10 ASA physical status 1 and 2 patients before (baseline) and after the administration of cimetidine to determine the in vivo effect of cimetidine on plasma cholinesterase (PCHE) activity. The in vitro effects of cimetidine at different plasma concentrations were also studied using the same blood samples. PCHE activity in the baseline samples was 432 +/- 4.6 (mean +/- SEM) U/ml, the dibucaine number 82. Administration of oral cimetidine (300 mg) the night before and 2 hours before surgery, failed to have any effect on PCHE activity (no in vivo effect). Plasma cholinesterase activity in the presence of cimetidine in vitro at plasma concentrations of 1.5, 15, 150, and 1500 micrograms/ml was 428, 420, 397, and 177 U/ml, respectively. Thus, in vitro data showed that cimetidine at plasma concentrations (1.5 to 15 micrograms/ml) achieved with clinical doses also has no effect on PCHE activity. PMID- 3337350 TI - Delayed respiratory depression in a child after caudal epidural morphine. PMID- 3337351 TI - Helium-induced errors in clinical mass spectrometry. PMID- 3337352 TI - Does diazepam really reduce the cardiotoxic effects of intravenous bupivacaine? AB - The effect of diazepam on the cardiovascular toxicity of bupivacaine was investigated in a rat model. Under chloral hydrate (400 mg/kg intraperitoneal) anesthesia, unilateral femoral venous and bilateral femoral arterial cannulae were placed for administration of drugs, for blood sampling, and for continuous qualitative monitoring of arterial blood pressure. Lead II ECG was continuously recorded and a tracheostomy performed to increase FIO2 by use of a "T-piece." Four groups of 24 to 36 rats each were studied. All rats received IV bupivacaine 2 mg/kg, within 10 seconds. Group I, the control group, received only bupivacaine. Groups II and III received IV diazepam 0.2 mg/kg, or diazepam vehicle in an equivalent volume, respectively. Five minutes after this pretreatment, groups II and III received IV bupivacaine 2 mg/kg. Group IV was given diazepam, 0.2 mg/kg, 30 seconds after injection of 2 mg/kg bupivacaine. A marked respiratory and metabolic acidosis occurred in all rats but was significantly worse in groups II and III. No rat in the study became hypoxemic. Serious arrhythmias (ventricular or supraventricular tachycardia) were noted in all groups, but the incidence was significantly higher in the group of rats given diazepam pretreatment than in the other three groups. It is concluded that IV diazepam 0.2 mg/kg given 5 minutes before administration of IV bupivacaine 2 mg/kg increases the incidence of serious cardiac arrhythmias. Second, this increase is not solely due to increased acidosis, because the rats receiving the vehicle (group III) developed equivalent acidosis but did not develop increased arrhythmias. PMID- 3337353 TI - The use of nitrous oxide is decreasing in Seattle. PMID- 3337354 TI - Temporomandibular joint subluxation on induction of anesthesia. PMID- 3337356 TI - Silent gene recognition. PMID- 3337355 TI - Control of cocaine-induced hypertension with labetalol. PMID- 3337357 TI - Epidural air bubbles and frothy syllogisms. PMID- 3337358 TI - The anesthesiologist outside the operating room: a new and exciting opportunity. PMID- 3337359 TI - Development of an anesthesiology-based postoperative pain management service. PMID- 3337360 TI - Treatment of air embolism with a special pulmonary artery catheter introducer sheath in sitting dogs. AB - The treatment of venous air embolism by aspiration from central venous catheters is well established. However, some anesthesiologists prefer to use a pulmonary artery catheter to monitor patients undergoing a neurosurgical procedure in the sitting position. While offering certain advantages, pulmonary artery catheters may be of limited use in the treatment of venous air embolism because the small diameter of the proximal port is poorly suited for efficient air aspiration. The authors have designed a special pulmonary artery catheter introducer sheath which can be positioned by intravascular electrocardiography to provide an efficient and effective means of air aspiration, while permitting the simultaneous use of a pulmonary artery catheter for pressure monitoring. The flow characteristics of this sheath, with and without side holes, were tested in vitro by measuring the time required to aspirate 50 ml of blood. The introducer sheath was compared to a Sorenson CVP catheter, a Bunegin-Albin Air Aspiration CVP Catheter, and the proximal port of a pulmonary artery catheter. The rank order of flow rate was: Bunegin-Albin CVP greater than introducer sheath without side holes = introducer sheath with side holes greater than Sorenson CVP greater than pulmonary artery catheter (P = 0.0001). The introducer sheath was then compared to a pulmonary artery catheter for the treatment of a 4 ml/kg venous air embolism in sitting, anesthetized dogs. The mean proportion of air retrieved by the sheath with or without side holes, 57% and 80%, respectively, was significantly greater than that retrieved by simultaneous aspiration of atrial and distal ports of the pulmonary artery catheter, 16% (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337361 TI - Accuracy of pulse oximetry during arterial oxyhemoglobin desaturation in dogs. AB - An animal model was developed to evaluate the accuracy of pulse oximetry over a wide range of oxyhemoglobin desaturation. The fractional inspired oxygen concentration was varied from 0.03-1.0 in five anesthetized dogs. One hundred and twelve simultaneous pulse oximeter oxygen saturation measurements (SpO2) and IL 282 CO-Oximeter arterial oxygen saturation (SaO2) measurements were made. Variance of SpO2 was increased for SaO2 less than 22%. Linear regression analysis of the data for SaO2 greater than 22% produced the equation y = 0.93x + 9.8 (r2 = 0.97). The mean difference between SpO2 and SaO2 was +5.5% +/- 4.2% (SD) over the range of 22-100%. Spectral analyses of oxygenated (O2Hb) and reduced (RHb) canine and human hemoglobins were performed. The absorption spectra of canine O2Hb and RHb were nearly identical to those of human O2Hb and RHb. Therefore, 1) SpO2 measurements in dogs at SaO2 greater than 22% are relatively accurate, and 2) hemoglobin absorption characteristics support the contention that such canine pulse oximeter studies can be extrapolated to humans. PMID- 3337362 TI - An in vitro evaluation of ionized calcium levels and clotting in red blood cells diluted with lactated Ringer's solution. AB - The addition of lactated Ringer's solution which contains calcium (RL) to citrated blood products poses a potential risk whenever the level of ionized calcium reaches a concentration capable of catalyzing the coagulation cascade. RL solution is used extensively as both a replacement and a maintenance fluid in the operating room. However, major surgical procedures often require replacement of blood components as well, during the operation. This study examines the in vitro propensity for coagulation when red blood cells (RBC) are diluted with RL. Seven mixtures with different ratios of RBC to RL were prepared from each of 23 units of RBC. These mixtures were analyzed for ionized calcium, total calcium, and pH, and were checked for any indication of coagulation. Nineteen additional RBC units were split into two parts which were mixed with equal volumes of normal saline (NS) or RL. These mixtures were filtered (40 micron) and the weight gain of the paired filters compared. From these studies, the authors identified a threshold value for ionized calcium (0.23 mM/L) below which the probability of clot formation is less than 0.01. This concentration is not reached if the RBC to RL volume ratio is 2:1 or greater. As much as 100 ml of RL can be added to a unit of RBC without exceeding the threshold value. Although not advocating the routine use of RL as a diluent for RBC, the authors conclude that, within the guidelines described, calcium containing salt solutions may be used to dilute blood products. PMID- 3337364 TI - The heat and moisture exchanger does not preserve body temperature or reduce recovery time in outpatients undergoing surgery and anesthesia. PMID- 3337363 TI - Pulmonary effects of crystalloid and colloid resuscitation from hemorrhagic shock in the presence of oleic acid-induced pulmonary capillary injury in the dog. AB - The effects of resuscitation with crystalloid and colloid solutions in the presence of increased pulmonary capillary permeability were studied. Twenty-four hours after oleic acid administration, dogs were anesthetized and bled to produce hemorrhagic shock. One hour later, resuscitation was performed with saline, 5% albumin, or 6% hydroxyethyl starch solution to restore and then maintain cardiac output at pre-oleic acid values for 6 h. Dogs were recovered and, 24 h later, were reanesthetized for final measurements. Oleic acid administration resulted in increases in pulmonary artery pressure, pulmonary vascular resistance, and extravascular lung water (EVLW). Resuscitation from hemorrhagic shock restored pulmonary hemodynamics to pre-hemorrhage levels and did not affect EVLW, PaO2, shunt fraction, dead-space-to-tidal-volume ratio, or pulmonary compliance. There were no differences in these parameters related to the choice of resuscitation fluid. Saline resuscitation markedly reduced plasma oncotic pressure and the plasma oncotic-pulmonary artery occlusion pressure gradient. Values for these two variables were markedly lower with saline than with colloid resuscitation. The authors conclude that the pulmonary effects of crystalloid and colloid solutions are similar in the presence of moderate increases in pulmonary capillary permeability. PMID- 3337365 TI - Supraventricular tachycardia associated with postpartum metoclopramide administration. PMID- 3337366 TI - Early anticoagulation peak and rapid distribution after intravenous heparin. PMID- 3337367 TI - Repeated anesthesia for a patient with neuroleptic malignant syndrome. PMID- 3337368 TI - The treatment of reflex sympathetic dystrophy with intravenous regional bretylium. PMID- 3337369 TI - An abnormal epiglottis as a cause of difficult intubation--airway assessment using magnetic resonance imaging. PMID- 3337370 TI - Identification of inadvertent intravenous placement of an epidural catheter in obstetric anesthesia. PMID- 3337372 TI - Comparison of ketanserin and sodium nitroprusside in patients with severe ARDS. PMID- 3337371 TI - Reduction cranioplasty and severe hypotension. PMID- 3337373 TI - Prevention of blood-borne infections in anesthesia personnel. PMID- 3337374 TI - Managing patients with AIDS--update. PMID- 3337375 TI - A further note on computer-assisted continuous infusion. PMID- 3337376 TI - Endotracheal intubation assisted with a pencil torch. PMID- 3337377 TI - Nitrous oxide and endotracheal tube cuff leaks. PMID- 3337378 TI - Is metocurine better? PMID- 3337379 TI - Separating the lungs of dogs without obstructing the right upper lobe bronchus. PMID- 3337380 TI - Intraoperative manipulation for positioning of double-lumen tubes. PMID- 3337382 TI - Does epidural anesthesia improve ventricular function? PMID- 3337381 TI - Methylene blue and pulse oximetry readings: spuriouser and spuriouser. PMID- 3337383 TI - On reducing the flammability of PVC. PMID- 3337384 TI - On the use of priming to test for anaphylactoid reactions to nondepolarizing muscle relaxants. PMID- 3337385 TI - Cardiovascular support drugs during thoracic epidural analgesia. PMID- 3337387 TI - Should multiorificed central venous catheters be heparin bonded? PMID- 3337386 TI - Epidural fentanyl is not effective for analgesia for extracorporeal lithotripsy (ESWL) PMID- 3337388 TI - Anesthesia mortality--a new mechanism. PMID- 3337389 TI - Effects of halothane, enflurane, and isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart. AB - To investigate the effects of volatile anesthetics on coronary blood flow (CBF) autoregulation and coronary vascular reserve, studies were performed on chronically instrumented dogs, awake and during the administration of 1.0 MAC halothane, enflurane, and isoflurane. Coronary pressure-flow plots were generated by measuring left anterior descending coronary artery blood flow while varying coronary inflow pressure with a hydraulic occluder. Autoregulation was quantitated by two measures: the slope of the horizontal "autoregulated" portion of the pressure-flow relationship and the autoregulation index (ArI) of Norris. Slope values (ml.min-1.mmHg-1 +/- SD) were: awake, 0.243 +/- 0.043; halothane, 0.414 +/- 0.044; enflurane, 0.587 +/- 0.187; and isoflurane, 0.795 +/- 0.246. The increase in slope was statistically significant only for halothane and isoflurane (P less than .05). The ArI approaches 1.0 when autoregulation is perfect, and approaches zero or is a negative number when autoregulation is absent. The authors found ArI values of: awake, 0.55; halothane, -0.08; enflurane, -0.01; isoflurane, -0.02. These values indicate good autoregulation while awake, but impaired autoregulation with all three anesthetics (P less than .05). Coronary vascular reserve was calculated, at a diastolic coronary pressure of 40 mmHg, as the difference between resting flow and flow during maximal coronary vasodilation induced by intracoronary adenosine. Coronary vascular reserve, maximal coronary conductance, and coronary zero-flow pressure were not significantly altered by these anesthetics. The authors conclude that 1.0 MAC enflurane, halothane, and isoflurane mildly disrupt CBF autoregulation, increasing CBF out of proportion to myocardial demands. Under the conditions of this study, these anesthetics do not affect maximal CBF or coronary vascular reserve. PMID- 3337390 TI - Unexpected cardiac arrest during spinal anesthesia: a closed claims analysis of predisposing factors. AB - Fourteen cases of sudden cardiac arrest in healthy patients who received spinal anesthesia were discovered in a preliminary review of 900 closed insurance claims for major anesthetic mishaps. All patients were resuscitated from the intraoperative cardiac arrest, but six suffered such severe neurologic injury that they died in hospital. Of the eight survivors, only one exhibited sufficient neurologic recovery to allow independence in daily self-care. In view of the unexpected nature of the cardiac arrests, as well as the ultimate severity of injury, these cases were analyzed in detail to determine whether there were recurring patterns of management that may have contributed to the occurrence or outcome of these anesthetic mishaps. Two patterns were identified. The first was the intraoperative use of sufficient sedation to produce a comfortable-appearing, sleep-like state in which there was no spontaneous verbalization. Cyanosis frequently heralded the onset of cardiac arrest in patients exhibiting this degree of sedation, suggesting that unappreciated respiratory insufficiency may have played an important role. The second pattern appeared to be an inadequate appreciation of the interaction between sympathetic blockade during high spinal anesthesia and the mechanisms of cardiopulmonary resuscitation. Prompt augmentation of central venous filing through the use of a potent alpha-agonist and positional change might have improved organ perfusion, shortened the duration of cardiac arrest, and lessened the degree of neurologic damage. PMID- 3337392 TI - Failure of pre-ischemic lidocaine administration to ameliorate global ischemic brain damage in the rat. AB - The cerebral protective effects of lidocaine were evaluated using a rat model of severe (near-complete) global ischemia produced by 10 min of bilateral carotid artery occlusion combined with systemic hypotension (MAP 45-55 mmHg). Prior to the induction of ischemia, 16 rats were given incremental doses of lidocaine intravenously until EEG slowing with sharp wave activity became evident. An equal number of rats (controls) received saline prior to the ischemic insult. Normoxia, normocapnia, and normothermia were maintained at all times. Following ischemia, the animals were allowed to recover. At 1.5 h post-ischemia, eight rats from each treatment group were reanesthetized, and regional brain water content was assessed gravimetrically. Brain specific gravity was significantly reduced from normal values in both treatment groups, and was unaltered by pre-ischemic lidocaine administration. Seven days post-ischemia, the remaining animals were reanesthetized; the brains were formalin fixed and processed for identification of irreversibly injured neurons in the hippocampus, neocortex, and caudate nucleus. Saline-treated rats displayed 75 +/- 4% (mean +/- SD) dead cells in the hippocampus (CA1); lidocaine-treated rats had similar injury (78 +/- 7%). In the neocortex and caudate nucleus, injury was graded as moderate, and no difference in severity could be distinguished between the treatment groups. The authors conclude that pre-ischemic treatment with maximal sub-epileptogenic doses of lidocaine had no effect on either early post-ischemic cerebral edema or delayed neuronal necrosis in this rat model of near-complete global ischemia. PMID- 3337391 TI - Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model. AB - Using the chronic maternal-fetal sheep preparation, nine pregnant ewes were studied to determine the effects of intravenous dantrolene sodium on maternal and fetal physiology, with particular reference to its placental passage, and its effects on uterine blood flow and uterine tone. Two doses of dantrolene sodium were studied: 1.2 mg/kg and 2.4 mg/kg. After 2.4 mg/kg, maternal cardiac output increased 29% (P less than 0.05) after 1 min and returned to normal after 30 min. Maternal mean arterial pressure increased 13% after 1 min and remained significantly elevated (P less than 0.01) for 3 h. No significant changes (P greater than 0.05) were observed in maternal heart rate, uterine artery blood flow, or central venous pressure. Maternal arterial pH declined from 7.42 to 7.39 (P less than 0.01) after 1 min and returned to baseline values after 10 min. Fetal heart rate decreased 24% (P less than 0.01) after 3 min and returned to normal after 10 min; the mean fetal arterial pressure remained unchanged (P greater than 0.05). Fetal arterial pH declined from 7.29 to 7.27 (P less than 0.05) after 1 min and remained significantly decreased for 120 min. Similar changes of lesser magnitude and shorter duration were seen following the 1.2 mg/kg dose. Maternal levels of dantrolene were less than 3 micrograms/ml. Although an equilibrium between maternal and fetal plasma dantrolene concentrations was apparent at 5 min, the fetal levels of dantrolene were approximately 10% of the mother's. The results indicate that the administration of intravenous dantrolene at 1.2 mg/kg or 2.4 mg/kg has no clinically significant adverse effect on mother or fetus in the sheep model. PMID- 3337393 TI - Cardiovascular interactions of lidocaine with verapamil or diltiazem in the dog. AB - Lidocaine in low and high doses was given by sequential infusions to isoflurane anesthetized dogs (1.75 +/- 0.03% end-tidal concentration) with or without concurrent infusions of diltiazem or verapamil, to assess changes in cardiovascular function. When lidocaine was administered alone, the low plasma levels (approximately 2 micrograms/ml) caused only a modest reduction in left ventricular dP/dt. The higher plasma lidocaine levels (approximately 6 micrograms/ml) reduced both left ventricular dP/dt and cardiac index, and increased pulmonary capillary wedge pressure and systemic vascular resistance. Diltiazem or verapamil, when administered alone at plasma concentrations of approximately 150-200 ng/ml, prolonged atrioventricular conduction, decreased heart rate and cardiac index, and, in the case of verapamil, also decreased left ventricular dP/dt and mean arterial pressure. When lidocaine was added to diltiazem or verapamil, the low plasma levels of lidocaine depressed cardiac function in the presence of either calcium channel blocking drug. In the presence of these levels of verapamil or diltiazem, only one of six verapamil-treated animals and three of six diltiazem-treated animals were able to maintain a mean arterial pressure greater than 50 mmHg with the higher dose of lidocaine. Caution may be advised if the addition of lidocaine, by whatever route, is indicated in subjects who have recently received intravenous verapamil or diltiazem. PMID- 3337394 TI - Chronic erythematous skin rash and thrush in a 16-month-old child. PMID- 3337395 TI - Further investigation into the recent increase in asthma death rates: a review of 41 asthma deaths in Oregon in 1982. AB - Vital statistics indicate increasing mortality from asthma since 1978 in the United States, England and Wales, Australia, and New Zealand. In Oregon and Washington, combined asthma mortality increased by 87% between 1977 and 1983. We reviewed the records of all patients (N = 41) (1) who died in hospitals or nursing homes in Oregon in 1982 and (2) whose death certificates listed asthma as the cause. Patients were 34 to 90 years old and half had been smokers. We found that most young patients who died clearly had asthma and died suddenly during severe attacks. Patients aged 55 and over frequently had bronchitis, emphysema, or chronic obstructive pulmonary disease rather than uncomplicated asthma, and were treated less aggressively than young patients. Their cause of death was often due to multisystem disease rather than reversible airflow obstruction. Reported statistics probably overestimate the true asthma mortality rate in the older population in Oregon. PMID- 3337396 TI - Antigen recognition in Filipinos, Japanese, Chinese, and Caucasians. AB - Allergic Chinese, Japanese, Filipinos, and Caucasian groups were compared and contrasted according to their skin test reactivity to pollens of grasses and trees. If a subject reacted to grasses, there was a significantly greater risk of reaction to trees (P less than .0005). The risk was profoundly greater in the three non-Caucasian groups (Filipino, Chinese, and Japanese) compared with the Caucasian group (P less than .0005). Reactivity to grass appeared to amplify the risk of reaction to trees. This effect was particularly striking in the non Caucasian groups. In groups that did not react to grasses, there was no difference between races in reactivity to trees. The non-Caucasian races did not demonstrate significant differences in their reaction to grasses. All three non Caucasian groups appear to be more sensitive than the matched Caucasians to cedar, cypress, and juniper. PMID- 3337397 TI - Improved diagnosis and treatment of allergic rhinitis by the use of nasal provocation tests. AB - A simple and safe method of nasal provocation for out-patients that requires no special equipment is described. A total of 2,645 cases were tested by nasal provocation tests. Of the total, 1,175 were tested with Dermatophagoides pteronyssinus, 825 with mixed grass pollens, 352 with plantain (Plantago lanceolata), and 125 for cats and correlating nasal tests with skin tests yielded 80%, 90%, and 85%, respectively. Immunotherapy for allergic rhinitis was only considered justifiable when the nasal provocation test was positive. The nasal provocation test was repeated at the end of the normal course of injections recommended by the manufacturer. If the nasal provocation test was still positive, further injections were given until the test became negative. This method of improving diagnostic accuracy and monitoring results of immunotherapy was used with both aqueous extracts which were used for skin testing (Australian Government Commonwealth Serum Laboratories) and with Allpyral pyridine-extracted alum-precipitated extracts (Dome Laboratories, England). The number of injections of allergen required to convert a positive nasal provocation test to negative varied from 26 to 69 for mite aqueous injections with only 12 to 19 for mite suspension and 47 to 98 for grass aqueous injections compared with 12 to 36 for grass suspension. Direct provocation tests of the nose should give a more accurate diagnosis than RAST or skin tests and are required for monitoring therapy because considerable individual variations in sensitivity and response to treatment were demonstrated. Standard dosage schedules are not suitable for individual patients, who should have their immunotherapy personalized. PMID- 3337399 TI - Dust mite avoidance in the treatment of asthma. PMID- 3337398 TI - Allergic bronchopulmonary aspergillosis in cystic fibrosis: a secretory immune response to a colonizing organism. AB - One hundred and seventeen patients with cystic fibrosis (CF) were evaluated for criteria suggestive of allergic bronchopulmonary aspergillosis (ABPA) and atopy. We found positive skin tests to Aspergillus to be more common in patients with CF than comparison groups with asthma or non-specific nasal symptoms. This increased prick skin test reactivity to Aspergillus was especially noticeable in a group of CF patients having only one or two skin tests positive, preponderantly Aspergillus. Twelve of the CF patients (10%) had further immunologic criteria suggestive of ABPA. These patients had significantly worse lung function than the CF patients without such criteria. PMID- 3337400 TI - Characteristics of emergency medicine fellowships. AB - Little has been reported in the literature on the characteristics of existing and planned emergency medicine fellowships. To help answer important questions about fellowships, a 28-question survey was developed by representatives from the University Association for Emergency Medicine education and fellowship committees, the Emergency Medicine Residents' Association, and a health services researcher. This questionnaire was sent to all emergency medicine residency directors and known emergency medicine fellowship programs. The results of our survey indicate that there are 18 current and 11 planned fellowships. The fellowships primarily last one year, are research oriented, and place a large emphasis on toxicology, emergency medical services, and critical care. They are based mostly in university or university-affiliated hospitals, and will graduate physicians who stay in academic emergency medicine. The major problems with fellowships include inadequate funding and lack of adequate candidates. PMID- 3337401 TI - Trauma and aging effects on hospital costs and length of stay. AB - Two hundred eleven consecutive admissions entered into the trauma registry of an inner-city hospital over a six-month period were studied. Length of stay, age, mechanism of injury, trauma score, gross financial charges, daily charges, and reimbursement rates were analyzed by linear multiple regression. Length of stay and gross financial charges were found to be significantly associated with age and trauma score. Daily charges were associated with length of stay and trauma score. Reimbursement rates were inversely associated with age and length of stay. The elderly make up a significant proportion of trauma victims and the cost of their care is higher than for younger patients. Because reimbursement for this age group is based largely on diagnosis-related groups, which pay only fixed costs, trauma centers must analyze the potential economic impact of older trauma victims. PMID- 3337402 TI - Dual residency programs. PMID- 3337403 TI - Skin testing in cases of possible crotalid envenomation. PMID- 3337404 TI - Documentation of informed consent. PMID- 3337405 TI - ATLS paradigm fails. PMID- 3337407 TI - Promoting patient satisfaction. PMID- 3337406 TI - Management of cyanide poisoning. PMID- 3337408 TI - The effect of ethanol on survival time in hemorrhagic shock in an unanesthetized swine model. AB - Controversy exists as to whether ethanol intoxication causes exaggerated hypotension or increased mortality during hemorrhagic shock. Previous studies have used anesthetized animals. This limits data interpretation as anesthetic agents, particularly pentobarbital, have well-documented effects on hemodynamics and the response to hemorrhage. We studied the effects of moderate ethanol intoxication on blood pressure and survival time during fatal hemorrhagic shock in unanesthetized swine. Immature female swine weighing 15 to 20 kg were splenectomized and instrumented with chronic indwelling aortic catheters, right atrial catheters, and gastrostomy tubes. Four to seven days later the unanesthetized animals underwent hemorrhagic shock. Thirty minutes prior to the start of hemorrhage, the experimental group (n = 8) received 3 mL/kg of 100% ethanol mixed as a 1:3 solution with water through a gastrostomy tube. The control group (n = 8) received an equal amount of water. The distal aortic catheter was connected to a roller pump and blood was removed at a rate of 1 mL/kg/min until the animal died. Arterial pressure, heart rate, lactate ethanol and glucose levels, hematocrit, and arterial blood gases were measured in both groups at baseline and every 15 minutes thereafter. A mean ethanol level of 1,500 to 1,700 micrograms/mL was produced in the experimental group from baseline through 60 minutes. Data were analyzed using Student's two-tailed t test, and analysis of variance for repeated measures. There was no significant difference in survival time between the control (63.1 +/- 2.8 min) and ethanol (59.9 +/- 5.9 min) groups. Systolic blood pressure was significantly lower in the ethanol group after 15 minutes of hemorrhage (81 +/- 22 to 59 +/- 14 mm Hg, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337409 TI - Lack of efficacy of 'weighted' radiographs in diagnosing acute acromioclavicular separation. AB - The efficacy of "weighted" films in diagnosing grade 3 acromioclavicular (AC) sprains not evident on plain (unweighted) films was evaluated. Eighty-three pairs of radiographs, taken with and without weights, of patients with suspected AC injury were studied. The films were read in a randomized and blinded manner by a staff radiologist. Criteria for classifying AC injuries were: grade 1, less than 3 mm (or less than 50%) difference between the AC widths with a normal coracoclavicular (CC) distance; grade 2, greater than or equal to 3 mm (or greater than or equal to 50%) difference between the AC widths with a normal CC distance; and grade 3, greater than or equal to 5 mm (or greater than or equal to 50%) difference in CC distance. In only three cases (4%) did weights cause the injured CC distance to increase and thereby unmask a grade 3 injury not evident on plain films. Further evidence that weights may not reliably elucidate the degree of AC joint injury is suggested by the fact that in several cases the weights actually caused the injured and uninjured CC distance to decrease. We conclude that the use of weighted radiographs lacks efficacy in unmasking grade 3 AC sprains on radiograph and we recommend that routine use of this technique be abandoned. PMID- 3337410 TI - The effect of axial traction during orotracheal intubation of the trauma victim with an unstable cervical spine. AB - Axial (in-line) traction is recommended as a stabilizing maneuver during orotracheal intubation of a trauma victim with a potential cervical spine injury. There are no published data demonstrating the safety of this technique in trauma patients with an unstable cervical spine. In our study, 17 victims of blunt traumatic arrest had radiographic analysis of the cervical spine during orotracheal intubation, with and without axial traction. Four (24%) had unstable injuries, which included a C6-7 fracture dislocation, a Hangman's fracture, and two atlanto-occipital dislocations. Axial traction during oral intubation in these victims resulted in a mean distraction at the fracture site of 7.75 mm. Axial traction produced 4 mm of posterior subluxation in the C6-7 fracture dislocation, demonstrating that axial traction alone may result in subluxation, as well as distraction. This depends on the direction of the traction force and integrity of surrounding tissues. We recommend that trauma patients requiring intubation prior to a complete examination and radiographic analysis of the cervical spine be nasotracheally intubated without axial traction, and that the head and neck be stabilized in the neutral position. If a contraindication to nasotracheal intubation exists, a cricothyroidotomy should be performed. PMID- 3337411 TI - Analysis of recreational off-road vehicle accidents resulting in spinal cord injury. AB - Twelve cases of spinal cord injury (SCI) resulting from recreational off-road vehicle (ORV) accidents seen during a three-year period at a spinal cord injury center were analyzed using structured interviews and record reviews. Seven accidents involved three-wheel all-terrain vehicles (ATVs), one involved a four wheel ATV, and four involved two-wheel trailbikes. The analysis of accident victim characteristics showed that all age groups are at risk, and that most victims were young adult men vehicle drivers with experience and wearing helmets. Spinal injury levels were cervical, three; thoracic, three; and thoracolumbar, six. Categorized accident hazard patterns were loss of control, six; tipover, four; and hidden obstacle, two. Contributing causative factors to the accident occurrence were poor driver judgment, seven, and vehicle instability, eight. Speeding was the most frequent primary cause of ORV accidents. We discuss vehicle and driver performance characteristics as they relate to risk of accident occurrence. The frequency of ORV accidents as an etiology of traumatic SCI at our center was 8%, compared to 8% for diving accidents and 11% for motorcycle accidents. We recommend, in view of the high risk of severe injury, widespread public education about ORV accident prevention. PMID- 3337412 TI - Evaluation of the effects of multiple-dose activated charcoal on the absorption of orally administered salicylate in a simulated toxic ingestion model. AB - The effects of multiple-dose activated charcoal administration on the absorption of orally administered salicylate were evaluated in a simulated overdose model. Thirteen adult volunteers were each given 24 81-mg aspirin tablets during a control phase, and during three randomized treatment periods the volunteers received 50 g activated charcoal for one, two, or three doses (separated by four hours). The control phase and treatment periods were separated by a one-week interval. Urine was collected for 48 hours to determine percent total salicylate excretion. Ten subjects completed all four phases of the study. Mean +/- SD percent recovery of salicylate from urine was: control, 91.0 +/- 6.12; one-dose charcoal, 68.3 +/- 12.46; two-dose charcoal, 65.9 +/- 13.48; and three-dose charcoal, 49.2 +/- 12.48. Each charcoal treatment significantly lowered the absorption of aspirin as compared with the control (P less than .01). There was no significant difference between one-dose and two-dose charcoal regimens. There was a statistically significant decrease in salicylate absorption with the three dose charcoal regimen as compared to one-dose and two-dose regimens (P less than .01). We conclude that activated charcoal is effective in inhibiting absorption of orally administered salicylate, in a small-dose aspirin ingestion model, with a three-dose multiple charcoal regimen being superior to either single-dose or two-dose regimens. PMID- 3337413 TI - Cephalic vein cutdown at the wrist: comparison to the standard saphenous vein ankle cutdown. AB - We first developed a technique for cutdown of the cephalic vein at the wrist. We then conducted a prospective cross-over cadaver study comparing the ability of medical students to perform this technique with that of the standard saphenous vein cutdown at the ankle. All students had a previous course in anatomy but had never performed a cutdown. Before testing, the students were given written material and a ten-minute lecture describing both approaches. Seventeen students performed 34 cutdowns; nine students attempted the cephalic cutdown followed by the saphenous cutdown; the remaining eight used the reverse order. The mean time (+/- SD) to isolation of the cephalic vein was 85 +/- 70 seconds; for the saphenous vein, mean time was 70 +/- 89 seconds (P = NS). There was one failure (inability to isolate the vein within five minutes) in 17 attempts at the cephalic vein and two failures in 17 attempts at the saphenous (P = NS). There were no complications (nerve, artery, or tendon injury) with either technique. The mean external vein diameter (+/- SD) of the cephalic vein and the saphenous vein were 3.2 +/- 1.0 mm and 3.6 +/- 0.7 mm, respectively (P = NS). We conclude that relatively inexperienced providers can learn to perform the cephalic vein cutdown at the wrist on fresh cadavers with similar speed and success as that for the saphenous vein cutdown at the ankle. Cutdown at this site may provide a useful alternative to the saphenous cutdown in certain clinical situations. PMID- 3337414 TI - Clinical, laboratory, and radiological information in the diagnosis of pneumonia in children. AB - The relative importance of clinical, laboratory, and radiological information in the diagnosis of pneumonia in children has not been extensively studied. In our study clinicians recorded clinical impressions and anticipated management prior to obtaining a chest radiograph and laboratory tests for 155 children in whom the diagnosis of pneumonia was being considered. This information was compared with the final diagnosis and management plans instituted after obtaining the radiograph and laboratory tests. Agreement occurred with the actual post radiograph plans in 78% of treatment decisions and in 88% of disposition plans made prior to obtaining the radiograph. The overall clinical impression was more important than individual signs, symptoms, or laboratory data in predicting the radiological diagnosis. No consistent pattern of signs, symptoms, and laboratory tests was found to be useful in making the diagnosis of pneumonia. PMID- 3337415 TI - Tracheal transection following blunt trauma. PMID- 3337416 TI - Fatal traumatic heart block as a result of apparently minor trauma. AB - We report a case of sudden death in an 18-year-old man who collapsed after falling prone onto a football. Although no external evidence of injury or cardiac contusion was noted, a right atrial endocardial tear extending through the conduction system was found at autopsy. This was thought to be responsible for his death and to explain the transient appearance of third-degree heart block during resuscitation. PMID- 3337417 TI - The spectrum of closed-head injuries in facial trauma victims: incidence and impact. AB - Little is known of the incidence of closed-head injury (CHI) associated with facial trauma. To study this problem, we conducted a retrospective review of 200 consecutive admissions to the University of Michigan Medical Center Emergency Department from 1980 to 1985 for treatment of acute facial fractures. All patients were admitted within 48 hours of injury (93% within 24 hours). Medical records were reviewed for age, sex, description, and circumstances of facial injury; assessment of loss of consciousness and anterograde amnesia; and associated intracranial or extracranial injuries. Seventy-three percent of the patients were men (mean age, 27.8 years). Etiologies, in descending order, were road traffic accidents (52%), assaults (22%), sports (14%), falls (7%), other injuries (3%), and gunshot wounds (2%). The incidence rate of CHI in our study was 55%. More than 90% of the head injuries were associated with the loss of consciousness of less than one hour. Risk factor analysis failed to demonstrate that an increased risk of CHI is associated with age, sex, or number of facial fractures. However, there was a one and one-halffold increased risk associated with patients involved in automobile accidents. PMID- 3337418 TI - Spontaneous rupture of the pulmonary artery. AB - A 45-year-old man presented with the sudden onset of diaphoresis, generalized weakness, and bilaterally achy arms. Physical examination revealed cyanosis of the head, neck, and upper chest with dyspnea and hypotension. He had distant heart sounds. An upright portable chest radiograph suggested widening of the mediastinum. A right arm venogram was consistent with extrinsic obstruction of the superior vena cava. A computed axial tomography scan demonstrated blood in the pericardium and indistinct widening of the pulmonary outflow tract. Autopsy revealed three tears of the pulmonary artery above the level of valve cusps, and thinning of the artery walls suggested cystic medial necrosis. These findings are suggestive of an acute spontaneous rupture of the pulmonary artery, possibly secondary to cystic medial necrosis. PMID- 3337419 TI - Tracheitis: the 'other' cause of upper airway obstruction. AB - A 22-year-old woman presented to an ear, nose, and throat clinic with an upper respiratory infection and sudden stridorous respirations. Aerosolized isoethrane therapy was beneficial and fiber-optic nasolaryngoscopy revealed a normal supraglottis and purulent intratracheal secretions. Secretions were cultured and grew Staphylococcus aureus and alpha hemolytic Streptococcus. IV cefazolin was initiated and the patient recovered without sequelae. This case illustrates a rare cause of upper airway obstruction, tracheitis. Tracheitis has been found in the pediatric literature. This is the first adult case reported in the literature. PMID- 3337420 TI - Treatment of a potentially lethal dose isoniazid ingestion. AB - A seven-year-old boy ingested 3,000 mg (125 mg/kg) of isoniazid. Initial blood levels of isoniazid were 250 micrograms/mL approximately six hours after ingestion. Despite IV treatment in the emergency department with 3,000 mg pyridoxine and a repeat of the same antidote one hour later in the intensive care unit, the high isoniazid blood levels and persistent metabolic acidosis and coma prompted a decision to increase drug clearance by hemodialysis. Clearance data confirmed the effectiveness of hemodialysis in removing the poison, and the clinical response was dramatic. PMID- 3337421 TI - Popcorn primary colonic phytobezoar. AB - A compulsive popcorn eater presented with complaints of abdominal and rectal pain, abdominal distention, and obstipation of one week's duration. Physical examination revealed a large lower abdominal mass, and roentgenograms demonstrated a large bezoar in the rectosigmoid region. This case describes the first report of a primary colonic bezoar caused by the ingestion of raw popcorn kernels. PMID- 3337422 TI - Exsanguinating hemorrhage from peripheral varicosities. AB - A 48-year-old woman presented to the emergency department in cardiovascular collapse after the onset of spontaneous bleeding from a noninflamed, nontraumatized varicose vein of the lower extremity. Despite successful immediate resuscitation she later succumbed to the sequelae of hemorrhagic shock. There was no evidence of coagulopathy or coagulation defect. No cardiovascular disease was found on autopsy. Although not common, spontaneous rupture of peripheral varicosities occurs often enough to be of concern. The pathologic lesions have been classified as acute and chronic, with acute lesions occurring in otherwise normal skin. Exsanguination from this source is not mentioned in standard texts, and only 27 cases have been reported in the literature. PMID- 3337424 TI - Cervical immobilization during orotracheal intubation in trauma victims. PMID- 3337423 TI - Toxic shock syndrome due to an infected human bite. AB - We report a case of nonmenstrual toxic shock syndrome. A 21-year-old man presented with severe pain in the right hand after an altercation in which he sustained a bite from a person. Physical examination revealed a small abscess on the right proximal interphalangeal joint with edema in the fourth and fifth digits and tenderness of the flexor sheath. The patient was hypotensive with diffuse macular erythematous skin. He responded to surgical drainage and antibiotics. PMID- 3337425 TI - The college--today and tomorrow. PMID- 3337426 TI - Emergency department observation units. American College of Emergency Physicians. PMID- 3337427 TI - Managed health care plans and emergency care. American College of Emergency Physicians. PMID- 3337428 TI - Analysis of growth plate abnormalities following intraosseous infusion through the proximal tibial epiphysis in pigs. AB - Intraosseous infusion has become an increasingly popular technique for vascular access in critically ill or injured children. Continuing acceptance of this procedure by physicians and possibly by prehospital personnel may lead to inadvertent placement through the immature growth plate. In our study, we intentionally penetrated the epiphyseal plate with the intraosseous needle and infused fluids in order to observe what complications, if any, might arise from this procedure. Twenty pigs 3 to 4 weeks old had a bone marrow aspiration needle introduced into the medullary cavity through the tibial epiphysis under fluoroscopic visualization. Sodium bicarbonate at 2 mEq/kg (n = 10) or 0.9 normal saline at 2 mL/kg (n = 10) was infused through the intraosseous needle. Radiographs of the involved growth plates were taken at two months and six months after infusion. No growth disturbances or growth plate abnormalities were detected clinically or radiographically through the rapid growth phase of the porcine tibia. Therefore, we believe that intraosseous infusion is a safe method of alternative vascular access associated with no significant growth defects despite injury to the developing growth plate from placement and infusion. PMID- 3337429 TI - Emergency department patient literacy and the readability of patient-directed materials. AB - There are 20 million American adults who cannot read. The demographics of the illiterate population suggest that they represent a significant proportion of patients cared for in a teaching hospital emergency department. This study was designed to assess whether readability of written material given to patients in a university hospital ED matched the literacy level of these patients. Data were gathered from 111 consecutive adult ED patients. Results of the survey showed that although the median education level of ED patients was 10th grade, more than 40% could not be expected to read at the 8th grade level, and at least 20% could be considered functionally illiterate. Readability of ED patient-directed materials was measured using the Fry index. Hospital and commercially generated patients education materials ranged from 8th to 13th grade level; a patient directed brochure from Virginia ACEP is written at a college reading level. Comprehension of the "leaving against medical advice" (AMA) form or a consent for surgery would require at least an 11th grade education. This study shows that there is an alarming discrepancy between ED patient literacy levels in our sample and the reading skills required to comprehend important written medical and legal information. More than 50% of ED patients in a teaching hospital may read below the level required to understand standard discharge instructions. In addition, understanding the "operative consent" and leaving AMA forms requires a level of education beyond that of the majority of ED patients. If patient-directed written material is to serve its purpose, then ED patient populations should be surveyed and the reading level of written material adjusted accordingly. PMID- 3337430 TI - Observation of head trauma patients at home: a prospective study of compliance in the rural south. AB - A prospective study was conducted to test the reliability of at-home observation of head trauma victims in the rural South among a population of low educational level. During a four-month period, 99 patients entered and 90 patients finished the study. In all cases, an individual was identified as willing to accept the responsibility of observing the patient. The observer received written and verbal instructions to stay with the patient for 24 hours and to wake the patient every four hours during that time. Patients then were contacted seven to nine days after their injury and questioned as to their present symptoms and observer compliance. For patients under 15 years of age (n = 34), the observer was questioned. Thirteen percent of the observers did not remain with the patient for 24 hours, 16% passed the responsibility of observation to another individual, and 71% awoke the patient as instructed. Observers who were not the patient's mother were significantly more likely to abandon the patient during the first 24-hour period. Observer compliance for patient awakening significantly decreased with the increase in patient age. When spouses and live-in friends were combined as a group of observers and compared with parents, the parents awoke the patient significantly more often. The authors conclude that in this population, at-home observation of head trauma patients, particularly those more than 25 years old, may not be reliable. Special attention should be directed toward the care of these patients. PMID- 3337431 TI - Echocardiography performed by emergency physicians: impact on diagnosis and therapy. AB - Echocardiography is the "gold standard" for diagnosing many cardiac and pericardial abnormalities. It is noninvasive and accurate, but in most emergency departments is only as available as the technician or the cardiologist. We describe our experience in training emergency physicians to perform cardiac ultrasound, and clinical situations in which we have found echocardiography to be useful. PMID- 3337433 TI - Propranolol toxicity presenting with early repolarization, ST segment elevation, and peaked T waves on the ECG. AB - A 58-year-old man presented stating that he had voluntarily ingested eight 80-mg propranolol tablets in approximately 24 hours. He was asymptomatic at the time of presentation. Subsequently, the patient developed only mild bradycardia. The ECG showed sinus bradycardia with striking early repolarization, ST segment elevation, and peaked T waves. These ECG abnormalities represent an unusual pattern for beta-adrenergic blocking agent toxicity. PMID- 3337432 TI - Fatality secondary to misuse of TAC solution. AB - The death of a 7 1/2-month-old girl from the misuse of tetracaine/adrenalin/cocaine solution for wound anesthesia is reported. Ten milliliters of the solution inappropriately came into contact with nasal mucous membranes, causing excessive drug absorption. The patient's death probably was due to cocaine toxicity (post-mortem blood level, 11.9 mg/L). PMID- 3337434 TI - Clonidine transdermal patch poisoning. AB - A case of infant clonidine poisoning from a transdermal patch that had been worn for five days by an adult and then discarded is described. The infant became hypotensive with a systolic blood pressure of 38 mm Hg, and a dopamine infusion was required for six hours to maintain adequate blood pressure. The infant was discharged 24 hours after admission. Clonidine toxicity, transdermal delivery system pharmacokinetics, and poison prevention are discussed. PMID- 3337435 TI - Defined criteria needed for ordering CT scans. PMID- 3337436 TI - Treatment of patients with ibuprofen overdose. PMID- 3337437 TI - Ibuprofen blood levels vary. PMID- 3337438 TI - Cocaine abuse and unusual injection sites. PMID- 3337439 TI - HMO patients with AMI: any difference in treatment? PMID- 3337441 TI - On-scene management of trauma patients by paramedics. PMID- 3337440 TI - Improving care for cervical spine injuries. PMID- 3337442 TI - Prolonged wound anesthesia is inappropriate. PMID- 3337443 TI - Board certification & emergency department coverage. PMID- 3337444 TI - Nurses excel as advocates for patients. PMID- 3337445 TI - RN follow-up plan helps high-risk infants. PMID- 3337446 TI - As I see it. Convention is investment in quality care. PMID- 3337447 TI - Let's sell activism as the benefit of membership. PMID- 3337448 TI - Pulmonary extraction of PGE1 in the adult respiratory distress syndrome. PMID- 3337449 TI - Clinically important respiratory effects of dust exposure and smoking in British coal miners. AB - A unique data set of 3,380 British coal miners has been reanalyzed with major focus on nonpneumoconiotic respiratory conditions. The aim was to assess the independent contribution of smoking and exposure to respirable dust to clinically significant measures of respiratory dysfunction. Exposure to coal-mine dust was monitored over a 10-yr period. Medical surveys provided estimates of prior dust exposure and recorded respiratory symptoms. Each man's FEV1 was compared with the level predicted for his age and height by an internally derived prediction equation for FEV1. Four respiratory indices were considered at the end of the 10 yr period: FEV1 less than 80%, chronic bronchitis, chronic bronchitis with FEV1 less than 80%, and FEV1 less than 65%. Results were uniformly incorporated into logistic regression equations for each condition. The equations include coefficients for age, dust, and when indicated, an interaction term for age and dust. Dust-related increases in prevalence of each of the 4 conditions were statistically significant and were similar for smokers and nonsmokers at the mean age (47 yr). There was no evidence that smoking potentiates the effect of exposure to dust. Estimates of prevalences at the mean age of all 4 measures of respiratory dysfunction were greater in smokers. At intermediate and high dust exposure the prevalence of the 4 conditions in nonsmokers approached the prevalence in smokers at hypothetically zero dust exposure. Both smoking and dust exposure can cause clinically important respiratory dysfunction and their separate contributions to obstructive airway disease in coal miners appear to be additive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337450 TI - Prolonged apnea associated with upper airway protective reflexes in apnea of prematurity. AB - We examined the hypothesis that most idiopathic prolonged apneic spells in preterm infants originate as a form of upper airway protective reflex. We elicited a previously described upper airway reflex in 10 sleeping preterm infants with apnea of prematurity by instilling physiologic saline into the oropharynx and recording respiration, heart rate, and swallowing. Immediately after a small pharyngeal bolus of warm saline, one or more of several characteristic airway reflex responses occurred with most stimulus trials. These responses included brief central apnea, swallowing, and obstructed inspiratory efforts. Intermittently, this response pattern was more extensive and resulted in prolonged apnea. We compared the frequency of prolonged apnea immediately after saline boluses with spontaneously occurring prolonged apnea and found that apnea frequency after saline was greater than spontaneous apnea frequency in all 10 infants (p less than 0.0025). Also, the incidence of prolonged apnea occurring immediately after saline stimuli was significantly greater than that after randomly delivered control stimuli (p less than 0.005). These observations indicate that saline can induce prolonged apnea. Swallowing, a distinctive feature of the chemoreflex, occurred during 76% of spontaneous prolonged apnea spells. Spontaneous and postsaline prolonged apnea were nearly identical with respect to general features and frequency of specific airway protective responses. We conclude that the majority of spontaneous prolonged apneic spells in preterm infants have multiple features that are characteristic of an exaggerated airway protective response to an upper airway fluid stimulus. Circumstantial evidence suggests that endogenous upper airway secretions may be an important source of stimuli-inducing apneic spells in preterm infants. PMID- 3337451 TI - Bronchodilator responsiveness in infants and young children with cystic fibrosis. AB - Response to the inhaled bronchodilator, metaproterenol, was evaluated in 28 outpatient infants and young children with cystic fibrosis (CF) (mean age, 16 months) and in 22 normal control children (mean age, 13 months). Lung function was assessed from partial expiratory flow volume curves generated by the rapid compression technique and was quantitated by the maximal expiratory flow at functional residual capacity (VmaxFRC). For the normal control group there was no significant change in VmaxFRC after the aerosol of either normal saline or metaproterenol. At baseline, the group of infants with CF had significantly lower values of VmaxFRC than did the normal control infants (202 versus 273 ml/s, p less than 0.05). The CF group demonstrated no significant change from baseline VmaxFRC after the aerosol of normal saline. However, after metaproterenol the CF group had a significant increase (p less than 0.001) in VmaxFRC, which eliminated the difference in VmaxFRC between the CF and normal control groups (267 versus 276 ml/s). We conclude that infants and young children with CF have increased bronchomotor tone and that bronchoconstriction represents a significant component of the airway obstruction present in patients with CF at this age. PMID- 3337452 TI - Changes in bombesin, calcitonin, and serotonin immunoreactive pulmonary neuroendocrine cells in cystic fibrosis and after prolonged mechanical ventilation. AB - Increases in bombesin, calcitonin, and serotonin immunoreactive pulmonary neuroendocrine cells have been documented in infants with bronchopulmonary dysplasia. As some of the secretory products of these postulated airway chemoreceptors are known to adversely affect pulmonary vasomotor and bronchomotor tone, the present study was undertaken to determine if similar changes occur in the lungs of older pediatric patients with chronic respiratory disease. Immunoreactive cells were identified using the antibody-peroxidase-antiperoxidase technique and expressed as immunoreactive bronchioles/cm2 of lung tissue. In subjects dying an accidental or noncardiopulmonary death (control group: n = 48, zero to 24 yr of age), the total number of bombesin, calcitonin, and serotonin immunoreactive bronchioles/cm2 was greatest at birth, then decreased rapidly to extremely low levels after the first year of life. In the cystic fibrosis (n = 55, 3 days to 29 yr of age) and prolonged ventilation (n = 24, 4 months to 18 yr of age) groups, there was a significant increase (p less than 0.035) in bombesin, calcitonin, and serotonin immunoreactive bronchioles/cm2 from 1 to 11 yr of age. In the cystic fibrosis group, there was a sixfold increase in the number of serotonin immunoreactive bronchioles/cm2 lung tissue (p less than 0.015) compared with that in the other 2 groups during the first decade of life, suggesting a response to specific factors present only in the lungs of patients with this disease. In all 3 groups, immunoreactive cells were infrequently identified after 11 yr, implying a fundamental change in neuroendocrine cell biology coincident with the termination of lung growth and/or the onset of puberty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337453 TI - The mechanical effects of expiratory airflow limitation on cardiac performance in cystic fibrosis. AB - The influence of altered lung mechanics on cardiac performance in cystic fibrosis (CF) was examined in an analysis of cardiorespiratory performance during exercise. The stroke volume (SV) response to exercise, derived from an indirect Fick (CO2) determination of cardiac output during submaximal steady-state exercise served as the index of cardiac performance. The relationship between exercising SV and forced expiratory volume in one second (FEV1), inspiratory duty cycle during exercise (Tl/Ttot) and exercising systemic arterial oxygen tension (PaO2) was examined in 15 studies involving 11 individuals with CF. The subjects were 12 to 25 yr of age and the FEV1 ranged from 15 to 72% predicted. Although a relationship existed between the SV expressed as a percentage of the mean predicted from height and gender (SV%) and PaO2 (r = 0.61, p less than 0.02), a more striking relationship was noted between SV% and either FEV1 or Tl/Ttot (r = 0.79 and 0.73, p less than 0.002). A multiple regression analysis of SV% identified an element of the relationship between FEV1 or Tl/Ttot and cardiac performance which was distinct from the influence of the coexisting hypoxia (p less than or equal to 0.05). The limitation in the SV response to exercise was noted to be in part reversible, coincident with an improvement in ventilatory mechanics that had occurred in 2 of the 4 persons in whom repeated studies were available. These observations suggest that in individuals with CF and a moderately severe degree of expiratory airflow limitation, there is a mechanical element of cardiopulmonary interdependence. PMID- 3337454 TI - IgA-driven antibacterial activity against Streptococcus pneumoniae by mouse lung lymphocytes. AB - To investigate the role of lung lymphocytes (LL) in the local defense mechanisms, we studied the natural antibacterial (NA) activity of mouse LL with an in vitro assay using S. pneumoniae type 3 as target. In parallel, natural killer (NK) activity against YAC-1 tumor cells was investigated. Lung cells obtained by enzymatic digestion were found to exert detectable NA and NK activities, which were further increased after purification of LL (greater than 90% lymphocytes) by carbonyl iron and magnet treatment. Depletion experiments with antibodies and complement indicated that the effector cell of NA activity was a Thy 1.2+, L3T4+, aGM1+ lymphocyte, whereas the effector of NK activity was found to have a Thy 1.2 , aGM1+ phenotype. Preincubation of LL with anti-IgA antibodies, but not with anti-IgG, completely inhibited NA activity, suggesting that it was mediated by preexisting IgA bound to the LL surface. Furthermore, purified IgA from S107 plasmacytoma with specificity for phosphorylcholine, a component of the outer wall of S. pneumoniae, was able to enhance the antibacterial activity of LL and to restore their activity after treatment with anti-IgA. In addition, S107 antibodies were found to specifically induce antibacterial activity against S. pneumoniae in resident alveolar macrophages (AM) and peritoneal exudate cells, which did not express NA activity. We conclude that mouse LL include a subset of IgA-bearing lymphocytes with the phenotype of helper-T cells, which are able to exert NA activity against pneumococcus through an IgA-driven mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337455 TI - Evidence that antituberculosis drugs are really effective in the treatment of pulmonary infection caused by Mycobacterium avium complex. AB - Successful chemotherapy of pulmonary disease caused by Mycobacterium avium complex by antituberculosis drugs has been reported by a number of investigators. However, no certain evidence of the efficacy has yet been demonstrated in a controlled clinical trial. The present study has approached this problem in 2 ways: serial analysis of minimal inhibitory concentrations (MIC) during treatment and correlation of response to therapy with initial MIC. It was observed that after administration of antituberculosis drugs (rifampin, isoniazid, kanamycin, enviomycin, and minocycline), MIC values for the M. avium complex strain increased significantly. This change may be considered a result of suppression of relatively susceptible bacteria and as evidence of the efficacy of drugs. Furthermore, a correlation between the MIC values determined before chemotherapy with the conversion of sputum to negative was shown. The M. avium complex strains varied markedly in their susceptibility to antituberculosis drugs, and these susceptibilities were correlated with the chemotherapeutic effect. The fate of patients seemed to be greatly influenced by the susceptibilities of the strains that caused infection. PMID- 3337456 TI - Pulmonary infection with nontuberculous mycobacteria. AB - Nontuberculous mycobacterial infections (NTM) are being increasingly recognized as a cause of chronic pulmonary disease. We recently reviewed the clinical, radiologic, and bacteriologic presentation of 89 adult patients ill enough to have been hospitalized between 1981 and 1985 with the diagnosis of NTM. Preexisting lung disease was present in 82% and alcohol abuse in 40%. Although M. avium complex was identified in 51% of the patients, M. xenopi, which is usually reported to occur infrequently, accounted for 38% of our cases and M. kansasii for only 9%. Treatment was limited by a high incidence of associated disease, in vitro drug resistance, drug toxicity, and a mortality rate of 32% within 18 months of admission. Nevertheless, bacteriologic conversion occurred in 29% of those treated. M. xenopi appears to be an important pathogen in southern Ontario. It differs from the other NTM by having a different pattern of in vitro drug resistance but not by its clinical or radiologic presentation. PMID- 3337457 TI - Respiratory control in presenile dementia. AB - To evaluate the role of the cerebral cortex in the response to externally added inspiratory flow-resistive load, we studied 7 patients manifesting clinical presenile dementia of the Alzheimer's type. All subjects exhibited diffuse cerebral cortical atrophy on computerized tomography of the brain. The mean age of the group was 45.6 yr. The rebreathing technique was used to assess minute ventilation (VE) and occlusion pressure (P100) responses to progressive hypercapnia. Rebreathing runs were performed before and during the addition of an inspiratory flow-resistive load of 18 cm H2O.L-1.s. The respiratory control data of these patients were compared with data obtained by similar techniques in a matched normal volunteer control group. In the patient group, with the addition of load, the VE/PCO2 response slope decreased (p less than 0.005), whereas the P100/PCO2 response slope did not significantly change. In the control group, P100/PCO2 response slope increased with load to maintain ventilation. These results suggest that in presenile dementia, during added inspiratory load, the drop in VE is associated with an inadequate increase in respiratory neuromuscular output. This lack of load compensation in patients with presenile dementia suggests a role for the cerebral cortex in the response to externally added load. PMID- 3337459 TI - The effect of chronic biphrenectomy on lung growth and maturation in fetal lambs. Morphologic and morphometric studies. AB - Three fetal lambs underwent phrenic nerve section between Days 99 and 104 of gestation, and 2 twins of the experimental animals underwent sham operation at the same time. When they were killed at 135 to 137 days of gestation, the experimental animals had lower specific lung weights (g/kg) and lung volumes (ml/kg) and had delayed lung development by subjective microscopy. Light microscopic morphometry showed significantly less volume proportion of potential gas-exchanging air spaces, less parenchyma, and more gas-exchanging wall. Scanning electron microscopy confirmed these findings and also showed that the transition zone between conducting and gas-exchanging areas was less sharp in the experimental animals, attributed to diminished alveolarization of distal conducting airways. Transmission electron microscopy, together with morphometry, showed a diminished maturation of alveolar Type II cells, with fewer osmiophilic lamellar bodies and more glycogen. The number of mesenchymal-Type II cell interconnections was not altered. Maturation of bronchiolar epithelium was not affected, and mesenchymal-epithelial connections were not observed. We conclude that bilateral phrenic nerve section not only diminishes lung growth, but also diminishes intrauterine maturation of the alveolar well. Maturation of bronchiolar epithelium may not be affected by fetal respiration. PMID- 3337458 TI - Experimental diabetes and the lung. I. Changes in growth, morphometry, and biochemistry. AB - Diabetes induced by streptozotocin at 3 wk of age in rats resulted in diminished somatic growth by 7 wk of age. Specific lung volume and weight (volume or weight per 100 gram body weight) were increased. The amount of lung DNA was decreased, and collagen and elastin were increased. The volume proportion of alveolar walls was increased at the expense of alveolar air. Air spaces were diminished in size, and alveoli increased in number. Total phospholipids and disaturated phosphatidylcholine (DSPC) were decreased, but they were normal relative to alveolar surface area. These changes reverted towards normal as a result of insulin treatment. Rats matched in weight (undernourished animals) for the diabetic animals showed relative preservation of lung weight, increased DNA, and reduced nonconnective tissue protein, RNA, collagen, and elastin. Air spaces were enlarged, alveolar surface area was decreased, and alveoli were decreased in number. Total phospholipids and DSPC were decreased, but normal when expressed per alveolar surface area. We conclude that diabetes and undernourishment have different effects on connective tissue synthesis in the lung that affect lung growth and structure, providing further evidence for the "fishnet" hypothesis of alveolar growth. PMID- 3337461 TI - Evidence of immunologic control of lung injury induced by trimellitic anhydride. AB - Trimellitic anhydride (TMA) is a chemical intermediate that has been shown to cause immunologically mediated respiratory syndromes in humans. We developed a rat model in which lung lesions accompanied by TMA-specific antibody resembled effects seen in humans. Two sets of experiments were undertaken to determine if TMA lung injury was primarily controlled by the immune system. Experiment 1: Rats were exposed to 95 micrograms/m3 of TMA 6 h/day, 5 days/wk for 2 wk during which time they received daily injections of either the immunosuppressant cyclophosphamide or saline. The TMA-exposed/saline control rats exhibited the usual TMA-induced lung lesions accompanied by TMA-specific antibody. However, the TMA-exposed/cyclophosphamide rats showed no lesions and no antibody. The spleen cells from all rats were subjected to lymphocyte blastogenesis assays using T- and B-cell mitogens. Results confirmed that cyclophosphamide-treated rats showed very little if any blastogenic response, whereas saline-treated rats gave the normal immune response. Thus, cyclophosphamide eliminated T- and B-cell function, which in turn prevented the occurrence of TMA lesions. Experiment 2: An initial passive transfer experiment showed that serum from TMA-sensitized rats could be adoptively transferred into naive recipient rats, which when given a single TMA inhalation challenge exhibited TMA-induced lesions. Similar attempts to transfer spleen cells or spleen cells plus serum did not predispose recipients for lesions. A second modified passive transfer of sensitized serum using a larger number of recipient rats, followed by a TMA challenge, resulted in lesions in 14 of the 16 rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337460 TI - Colchicine suppresses the release of fibroblast growth factors from alveolar macrophages in vitro. The basis of a possible therapeutic approach ot the fibrotic disorders. AB - Fibrosis is the accumulation of fibroblasts and the connective tissue products secreted by these cells, usually subsequent to tissue injury. While fibrosis can be useful in preserving the general structural integrity of a tissue, it often alters cell-cell and cell-connective tissue interactions, which leads to loss of tissue function. On the basis of the concept that mononuclear phagocytes can direct the development of fibrosis through the release of specific mediators that stimulate fibroblast proliferation, we propose a therapeutic strategy to prevent fibrosis by preventing the release of these specific mediators. The present study demonstrated that colchicine, a widely used and well-tolerated drug, can block alveolar macrophage release of 2 mediators associated with the development of fibrosis in interstitial lung diseases, fibronectin, and the alveolar-macrophage derived growth factor (AMDGF). Colchicine blocked the spontaneous release of fibronectin by alveolar macrophages obtained from patients with fibrotic lung disease by 23 +/- 4% after 24 h and by greater than 90% after 72 h. AMDGF release was blocked by 68 +/- 10% after 4 h (p less than 0.01, all comparisons). The effect of colchicine was not due to nonspecific toxicity since [14C]proline tracer studies demonstrated that macrophages treated with colchicine were capable of de novo protein synthesis and the secretion of several protein products, despite the fact that fibronectin and AMDGF release were suppressed. The effect of colchicine on the spontaneous release of both fibronectin and AMDGF could be observed at concentrations less than 10 ng/ml, levels that can be achieved in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337463 TI - Albuterol has no effect on diaphragmatic fatigue in humans. AB - Diaphragmatic fatigue may play an important role in precipitating acute respiratory failure. Pharmacologically, theophylline and beta-2 agonists have been used to improve diaphragmatic contractility. We designed experiments to study the effects of albuterol, a beta-2 agonist, on diaphragmatic fatigue in humans. In 5 normal subjects, fatigue was induced by breathing through an inspiratory resistance. Studies were done at 2 levels of diaphragmatic tension time index (TTdi) of 0.25 and 0.30. At each TTdi, either placebo or albuterol (4 mg three times daily) was taken for 3 days. All subjects experienced side effects of sympathetic stimulation. Albuterol did not significantly increase the strength of the fresh diaphragm. With a TTdi of 0.25, values for mean endurance time were 649 +/- 250 (mean +/- SE) and 552 +/- 161 s, respectively, in placebo and albuterol runs. Respective values for TTdi of 0.30 were 109 +/- 14 and 143 +/- 27 s. During recovery, the mean values for the time needed for maximal transdiaphragmatic pressure (Pdimax) to reach 90% of the prefatigue Pdimax were 891 +/- 370 and 1043 +/- 394 s, respectively, for placebo and albuterol runs (TTdi = 0.25). Respective values for TTdi of 0.30 were 219 +/- 57 and 231 +/- 108 s. We conclude that, in humans, albuterol has no significant effect on the strength of the fresh or fatigued diaphragm, diaphragm endurance time, or the recovery of Pdimax from fatigue. PMID- 3337464 TI - Fabrication of a customized cuirass for patients with severe thoracic asymmetry. AB - We describe the fabrication of customized cuirasses for patients with severe thoracic asymmetry who need assisted ventilation. The materials and methods for this technique are available in most hospital-based or commercial orthotics laboratories. The degree of innovation required for fabrication should be within the capabilities of most certified orthotists. This specialized application is highly effective in selected patients, as reported by us and other investigators. PMID- 3337462 TI - A serial immunologic and histopathologic study of lung injury induced by trimellitic anhydride. AB - Trimellitic anhydride (TMA) can induce immunologic lung disease in exposed workers. We have developed a rat model of TMA lung injury characterized by lung hemorrhage and an immune response to trimellityl (TM) haptenized lung proteins. The model is similar to the pulmonary disease-anemia syndrome (PDA) seen in workers exposed to TMA fumes. Sprague-Dawley rats, 15 per exposure period, inhaled micronized TMA powder, 100 micrograms/m3, 6 h/day, for 2,6, or 10 days and were sacrificed. At each time period, total, IgG, IgA, and IgM antibody to TM rat serum albumin (TM-RSA) were measured by radiolabeled antigen binding and enzyme-linked immunosorbent assay (ELISA) in serum and bronchoalveolar lavage fluid (BAL). Hemorrhagic lung foci, weight, and displacement volume were determined, and lungs were examined by light and electron microscopy. There was no lung injury or antibody response at 2 days. There was minimal lung injury at 6 days with low levels of antibody in BAL and serum. At 10 days, there was a marked increase in hemorrhagic foci and in BAL and serum antibody levels. BAL antibody levels at 6 and 10 days had higher correlations with measures of lung injury than corresponding serum levels. There was minimal ultrastructural change at 6 days. By Day 10, there was marked intraalveolar hemorrhage, alveolar septal inflammatory nodules, abundant alveolar macrophages, and evidence of endothelial and epithelial cell injury. These results indicate that the immune response to inhaled TMA occurs parallel with the development of lung lesions, and antibody levels in BAL and serum are highly correlated with lung injury. PMID- 3337465 TI - Inaccurate oxygen delivery in some portable liquid oxygen devices. AB - After documenting that the measured flow from a portable liquid oxygen device was different from the set flow and that this difference caused hypoxemia in a patient with chronic obstructive pulmonary disease, we compared the measured and set flows from 23 portable devices supplied by 2 different providers. Nine of 13 devices (69%) from Provider A gave measured flows that differed from the set flows at 14 of 65 (21%) settings (13 devices times 5 flow settings). Three of 10 devices (30%) supplied by Provider B gave measured flows that differed from the set flow in only 5 of 50 (10%) possible settings (10 units times 5 flow settings). Oxygen delivery may be inaccurate from portable liquid systems serviced by some suppliers. This problem may cause patients to become hypoxemic despite using the devices in the prescribed fashion. PMID- 3337466 TI - Variability of the perceived sense of effort in breathing during exercise in patients with chronic obstructive pulmonary disease. AB - The present study examined the reproducibility with which subjects with stable chronic obstructive pulmonary disease (COPD) scale the sense of effort involved in breathing during exercise. The sense of effort was assessed in 6 subjects with COPD during bicycle exercise continued to a symptom-limited maximal work load using a conventional category scale. Reproducibility of the sensory experience was assessed by comparing results obtained from 3 incremental work tests, 2 on the same day and a subsequent test performed within 1 to 10 days. During all trials in all subjects, sensory scores correlated closely with both minute ventilation and oxygen consumption (r greater than or equal to 0.92 for both VE and VO2). The average coefficients of variation for the maximal Borg Score and Borg Score at 2 min of exercise for the group as a whole were 3 +/- 1 and 3 +/- 2% (SE), respectively. Variability in sensory scores was not significantly different on exercise trials performed either within or between days. Furthermore, variability of sensory scores, oxygen consumption, heart rate, or minute ventilation were similar. We conclude that when using a category scale in subjects with COPD, the perceived sense of effort in breathing during exercise is highly reproducible, correlates closely with physiologic measures defining the intensity of exercise, and is no more variable than physiologic parameters typically measured during an exercise test. PMID- 3337467 TI - Association of plasmids and virulence of Mycobacterium avium complex. AB - Mycobacterium avium complex strain LR25, which carries 3 plasmids, was shown to be of high virulence in beige mice as judged by high mortality and a progressive increase in organisms in the spleen and lungs determined by counting the number of colony-forming units. Strain LR163, a "cured" derivative of LR25 that lacks all 3 plasmids, was of low virulence as judged by these criteria. The relative virulence of the strains was confirmed by studies of oxygen metabolite (superoxide anion and hydrogen peroxide) release from resident and BCG-activated mouse peritoneal macrophages. In contrast to loss of virulence, no significant change was seen in drug susceptibility. PMID- 3337468 TI - Chemotactic enhancement by lavaged proteins. PMID- 3337469 TI - More on the research-training debate. PMID- 3337470 TI - Maternal smoking and bronchial responsiveness in children. PMID- 3337472 TI - Asbestos bodies in bronchoalveolar lavage fluid and in lung parenchyma. AB - Numerical concentrations of asbestos bodies (AB) were measured by light microscopy both in samples of bronchoalveolar lavage (BAL) fluid and in samples of lung parenchyma from 69 patients with suspected asbestos-related diseases who had had lavages and later open lung biopsies or autopsies. Objectives were to study the recovery of pulmonary AB by BAL and the ability of BAL concentrations to predict parenchymal concentrations. BAL and parenchymal concentrations were both spread over 6 orders of magnitude and were positively correlated (r = 0.74 between logarithmic values). It is believed that, by a process of progressive elution, AB firmly adherent to the alveolar wall become suspended in BAL fluid; such suspended bodies represent roughly 2% of all the bodies stored in the portion of lung lavaged. Recovery is associated with great interindividual variations. When a measured BAL concentration exceeds 1 AB/ml, it can be quite confidently predicted, however, that the parenchymal concentration is in excess of 1,000 AB/g and that the patient has experienced a nontrivial asbestos exposure. PMID- 3337471 TI - Pulmonary extraction and pharmacokinetics of prostaglandin E1 during continuous intravenous infusion in patients with adult respiratory distress syndrome. AB - Prostaglandin E1 (PGE1) is currently being evaluated in clinical trials to determine its usefulness in the treatment of adult respiratory distress syndrome (ARDS). The drug is administered to ARDS patients by continuous intravenous infusion at dosage rates of up to 30 ng/kg/min for 7 days. The present study was conducted to determine the pulmonary extraction efficiency and pharmacokinetics of PGE1 under these conditions. Plasma levels of PGE1 were determined by high performance liquid chromatography in 14 patients who either had ARDS or were considered to be at risk of developing ARDS following trauma or sepsis. Predose plasma levels of PGE1 were below the detection limit of the assay (50 pg/ml). At a dosage rate of 30 ng/kg/min, pulmonary arterial and systemic arterial plasma levels ranged from 265 to 1,009 pg/ml and 50 to 796 pg/ml, respectively. The pulmonary extraction ratio (Ep) of PGE1 varied from 0.11 to 0.90 and was independent of dose but dependent on cardiac output. The data were adequately described by first-order pharmacokinetic equations which assumed that the lung was the only site of PGE1 clearance. Nine of 10 patients with AaPO2/FlO2 below 510 mm Hg had Ep greater than 0.7 and high pulmonary intrinsic clearance for PGE1 (ca. 250 L/min), but all 4 patients with AaPO2/FlO2 above 510 mm Hg had Ep less than 0.6 and low intrinsic clearance (ca. 37 L/min or less). The intrinsic clearance of the lung for PGE1 in ARDS patients therefore appears to decrease abruptly once a threshold of severe respiratory failure is achieved. PMID- 3337474 TI - Open lung biopsy in patients with diffuse pulmonary infiltrates and acute respiratory failure. AB - Patients with diffuse pulmonary infiltrates and acute respiratory failure (ARF) potentially can benefit from diagnostic information provided by open lung biopsy (OLB). To better quantify possible benefits and risks, we reviewed an 11-yr experience with 80 such patients. Although OLB did provide a specific etiologic diagnosis in 53 patients (66%) and did influence therapy in 56 patients (70%), only 24 patients (30%) survived to hospital discharge, and 9 patients (11%) survived for 1 yr or more. Survival rates did not depend on the availability of a specific diagnosis, changes in diagnosis, or changes in therapy. Survival was improved in younger patients and patients not requiring preoperative mechanical ventilation. Fifteen patients (19%) suffered complications possibly related to OLB; the survival rate to discharge was decreased in these patients, although not significantly. We conclude that OLB provides a specific etiologic diagnosis in many patients with diffuse pulmonary infiltrates and ARF, but that its utility in these patients is limited by current shortcomings of therapy. PMID- 3337475 TI - Surgeons can change the world. PMID- 3337473 TI - Uniformity of bronchoalveolar lavage in patients with pulmonary sarcoidosis. AB - Sarcoidosis is a granulomatous disease of unknown cause characterized by a lymphocytic alveolitis. Previous studies have shown that the inflammatory cell population of the distal lung units of patients with this disorder can be accurately assessed using bronchoalveolar lavage (BAL). The present study evaluated the uniformity of BAL between different sites of the lung in patients with sarcoidosis. In general, there was a good correlation between sites for percentages of lymphocytes (LYM) (r = 0.750, p less than 0.0001), LYM number (r = 0.356, p = 0.0007), percentages of neutrophils (NEUT) (r = 0.917, p less than 0.0001), NEUT number (r = 0.999, p less than 0.0001), and macrophage (MAC) number (r = 0.858, p less than 0.001). Despite the good overall correlation, we found that 43% of the patients with high percent LYM (greater than 30%) had this finding on one side only. These patients did not differ from the group as a whole based on radiographic stage of their disease but did differ in the number of radiographs demonstrating focal infiltrates (2 of 28 patients with both sides less than 30% LYM, 2 of 14 with both sides greater than 30% LYM, and 4 of 9 with only one side greater than 30% LYM p less than 0.05 by chi-square); and in each situation the highest percent LYM was seen on the side with focal changes on the chest radiograph.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337476 TI - Surface oximetry. A new method to evaluate intestinal perfusion. AB - Accepted methods to evaluate intestinal vascularity intraoperatively include standard clinical criteria (SCC), doppler ultrasound (DUS), and intravenous fluorescein (FLF). A combination of methods is often used to overcome disadvantages of individual techniques. Assessment of intestinal vascularity by FLF was compared to SCC, DUS, and pulse oximetry (POX) in segments of intestine demonstrating arterial, venous and arteriovenous occlusion, to determine if POX might supplement the assessment of intestinal vascularity. POX uses a commercially available instrument to assess tissue oxygenation and arterial flow, and is rapid, reproducible, and noninvasive. POX appears to be a superior technique when compared to SCC and DUS. PMID- 3337477 TI - Management of recurrent duodenal ulcer disease. AB - The purpose of this project was to evaluate the medical and surgical treatment of patients with recurrent peptic ulcer disease and to determine whether the addition of cimetidine has altered the treatment outcome. The authors studied 42 patients with recurrent ulcers after duodenal ulcer surgery. Four patients underwent emergency operation for ulcer-related complications, while 38 patients received medical therapy including cimetidine as initial treatment. Medical therapy achieved good results in 18 of 38 patients (47%). The remaining 20 patients either were treated surgically (14) or are still symptomatic. Four of the 18 patients managed operatively had a second recurrent ulcer (22%). There were no deaths. Thirty-two of the original 42 patients (76%) were helped by the treatment. It was concluded that cimetidine has improved medical therapy compared with historical controls but that operative treatment is indicated in about one half of patients with recurrent peptic ulcer disease. PMID- 3337478 TI - Unsuspected perforation in bleeding duodenal ulcers. AB - A combination of bleeding and perforation rarely occurs simultaneously in peptic ulcer disease. The charts of 127 patients undergoing surgery for either complication were reviewed (bleeding, 91; perforation, 36). Nine of 91 (9.9%) patients in the bleeding group were found at operation to have a unsuspected perforated duodenal ulcer. The operative mortality in the patients with the combined complications (44%, 4/9) was significantly higher than that in patients with bleeding alone (8/82, 9.8, P less than 0.001) or those with perforation alone (4/36, 11.00, P less than 0.025). The mean age of nonsurvivors was significantly higher than that of the survivors (74 +/- 8.01 vs 50.4 +/- 5.65 years, P less than 0.005). The duration of symptoms until operation was longer in patients who died (63 +/- 12.7 hours) than in survivors (40.2 +/- 6.02 hours, P = NS). All patients who died, and three of five survivors, had preoperative fever (greater than 99.0 F), leukocytosis (greater than 12,000/mm3), and persistent tachycardia despite adequate hydration and blood replacement. Perforation in bleeding peptic ulcers is not an uncommon finding, and was present in 9.9 per cent of patients. The presenting symptom of bleeding may obscure signs of perforation, delay surgery, and contribute to the higher mortality rate. The presence of fever, leukocytosis, and tachycardia despite adequate fluid and blood replacement warrants a suspicion of perforation in patients with bleeding peptic ulcer. PMID- 3337479 TI - Biliary reconstruction without transanastomotic stent. AB - Twenty three operations for common bile duct (CBD) stricture were performed on 22 consecutive patients by a single surgeon without the use of transanastomotic stents. All strictures resulted from operative injury; four were acute (less than 1 month postinjury), and 18 were treated a mean of 44 months (2-124 months) after injury. All but two of these patients had had previous repair attempts. Mean follow-up after reconstruction was 72 months (17-128 months). Reconstructive procedures included hepaticojejunostomy seven, choledochojejunostomy ten, and choledochoduodenostomy six. Twenty one of the 22 patients (95%) have had excellent results, with stable liver function an no evidence of cholangitis or jaundice. Early postoperative complications (one abscess, one fistula) resolved. In two of the 22, stricture recurred at one and five months, requiring balloon dilatation in one and reoperation in the other. Both are now asymptomatic at 37 and 64 months. Reoperation was also required to remove an infected distal CBD stump in one patient 29 months after reconstruction, and another had mild intermittent cholangitis, now resolved. The only death occurred 70 months after reconstruction in a patient who developed biliary cirrhosis. These results suggest that biliary enteric anastomosis for acute and chronic bile duct strictures associated with benign disease can be performed without stenting, yielding low postoperative morbidity and excellent long-term patency. PMID- 3337480 TI - Selective intraoperative cholangiography. A case for its use on an anatomic basis. AB - The routine use of intraoperative cholangiography has vastly improved the results of common duct exploration by reducing the number of negative explorations. The controversy surrounding the use of routine versus selective intraoperative cholangiography has centered on the incidence of unsuspected common-duct stones. A prospective study was designed to examine both preoperative clinical data and intraoperative anatomical information to determine criteria that would identify patients who would not require cholangiography. One hundred consecutive patients undergoing cholecystectomy were included in the study. When considering patients without preoperative clinical data suspicious for common duct stones three anatomical conditions were identified in which common duct stones would not be present: cystic duct less than 3 mm; smallest stone size greater than 6 mm; a single stone. Using intraoperative criteria as a basis for cholangiography, 44 per cent of patients without clinical suspicion of common duct stones would be spared an intraoperative cholangiogram. It is the authors' opinion that the addition of anatomic findings to preoperative clinical data can further reduce or eliminate the risk of unsuspected stones while sparing a large number of patients the risk and expense of routine intraoperative cholangiography and possible negative duct exploration. PMID- 3337481 TI - Cholecystectomy in the elderly. AB - A two-year retrospective review of 137 patients over 70 years of age undergoing cholecystectomy, from January 1, 1983 to January 1, 1985, was done at Mount Sinai Medical Center of Miami Beach. This study focused on the clinical presentations, surgical management, and overall morbidity and mortality of this operative procedure in the elderly. There were 81 women and 56 men in the study ranging in age from 70 to 96. Elective procedures were performed in (78/137) 57 per cent of the patients while (59/137) 43 per cent underwent emergency surgery. Elective procedures were performed in (55/81) 68 per cent of the women and (23/56) 41 per cent of the men. Emergency surgery was required in (26/81) 32 per cent of the women and (33/56) 60 per cent of the men. Complications developed in (16/78) 20 per cent of the elective cases and (19/59) 32 per cent of the emergency cases. In the elective group, the most common complication involved the cardiovascular system. Sepsis with multiple organ failure accounted for all the deaths in the emergency group. Among the 137 patients in this series, there was a (3/78) 3.8 per cent mortality in the elective group and a (7/59) 12 per cent mortality in the emergency group with an overall mortality of (10/137) 7.3 per cent. The purpose of this study was to highlight the necessity for aggressive surgical management of biliary tract disease in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337483 TI - Percutaneous catheter drainage of abscesses associated with enteric fistulae. AB - In the past six years, percutaneous catheter drainage (PCD) has been performed in the treatment of 99 patients with abdominal and retroperitoneal abscesses. Of these 99 patients, 15 had abscesses associated with an enteric fistula. Fistula sites included small bowel (five), colon (three), complex (three), duodenum (two) and one each for the stomach and common duct. Two of these 15 patients had an initially successful PCD, ten developed recurrent abscesses after the first PCD and the procedure failed in the remaining three patients. Of the ten patients with recurrent abscesses, eight were successfully treated by a second PCD while two required small-bowel resection. Of the three failures, all three required operation and eventually died of septic complications. The diagnosis of fistula was made at the initial PCD in only six of 15 cases. There was a significant correlation between PCD failure and presence of an enteric fistula (P less than 0.001 by chi-square test). These data suggest that the diagnosis of fistula associated with abdominal abscess is elusive, but once established, most recurrent abscesses can be successfully treated by a second PCD. Operative treatment of recurrent fistula-related abscesses should be reserved for persistent fistula drainage after a second PCD or for unresolved sepsis following the initial PCD. PMID- 3337482 TI - Surgical complications of human immunodeficiency virus infection. AB - To assess the role of the general surgeon in the care of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) the hospital records of all patients with AIDS or ARC who underwent a major operation at the General Surgical Service of Crawford W. Long Memorial Hospital were reviewed. Of 79 patients with AIDS or ARC diagnosed since 1982, 14 required major abdominal surgery. Operations performed were for gastrointestinal (GI) complications of opportunistic infections and neoplasms (four), diagnosis of major retroperitoneal lymphadenopathy (four), and treatment of AIDS-related immune thrombocytopenia (six). GI complications consisted of two cases of cytomegalovirus perforation of ileum and colon, one case of bleeding ileocolonic lymphoma, and one case of cryptosporidium cholecystitis. Laparotomy for diagnosis of retroperitoneal lymphadenopathy was performed in four patients and provided diagnostic material in three of them. Six patients underwent splenectomy for AIDS-related immune thrombocytopenia. Four of these patients had previously been treated with prednisone without impressive results. All patients had marked improvement of their platelet counts and clinical bleeding after splenectomy. Postoperative complications were common and consisted of wound infection, disseminated intravascular coagulation, GI bleeding, pneumocystis pneumonia, small-bowel obstruction, and cytomegalovirus pneumonia. One patient died after laparotomy for perforated ulcers of the ileum and colon. PMID- 3337484 TI - Myocardial infarct extension: occurrence, outcome, and risk factors in the Multicenter Investigation of Limitation of Infarct Size. AB - The occurrence, outcome, and predictors of myocardial infarct extension were determined in 848 patients with acute myocardial infarction. An increase in the level of plasma MB creatine kinase activity was used to detect extension, which occurred in 71 of 848 patients (8.4%). For these patients, hospital mortality was more than four times higher than for those without extension (30% versus 7%, P less than 0.01). However, for patients surviving the initial hospitalization, there was no significant difference in mortality during the following year (12% compared with 9%). Multivariable analyses indicated that extension was more likely to occur in patients with recurrent ischemic pain during the second hospital day, a history of previous myocardial infarction, and ST segment depression on the admission electrocardiogram. The occurrence of extension in patients with two of these risk factors was more than twice that of patients without any of the risk factors (15.1% compared with 5.8%). Patients with these risk factors should be considered for early coronary angiography and possible intervention to prevent infarct extension and its sequellae. PMID- 3337485 TI - Internal medicine in the National Resident Matching Program 1987: the ides of March. AB - The number and percentage of graduating seniors from medical schools in the United States who have matched to categorical programs in internal medicine in the National Resident Matching Program have decreased since 1985. Examination of the balance between undergraduate and graduate medical education in the 127 networks of each medical school in the United States and its associated hospitals showed major differences in the retention and recruitment of graduates. The service needs of hospitals rather than the number of graduates from schools in the United States would seem to have controlled the number of positions. Because the positions exceeding the number of graduates from the United States are filled by graduates of foreign schools, these positions are of major importance in determining the supply of internists. The clerkship programs must be restructured to provide students an improved introduction to internal medicine, and the number of entering positions in residencies must be reduced by the substitution of other personnel to do some of the service functions now done by residents. PMID- 3337486 TI - The standard of care: a case report and ethical analysis. AB - Physicians increasingly allow their perceived legal responsibilities to displace their clinical judgment. Misunderstandings that surround the term "standard of care" have encouraged fears of liability and have led to the practice of defensive medicine. Physicians may consider the standard of care to be a technical or legal obligation, but an optimal standard would be one based on detailed knowledge of a patient's medical history and personal condition. It would include the physician's clinical judgment, which integrates specific technical and legal information with clinical experience in caring for patients. Occasionally, such judgment may conflict with the rulings of a court, which considers technical and legal information without the benefit of clinical judgment. Physicians must be prepared to be advocates for their patients, especially when legal proceedings are flawed or injurious. Systematic processes of examination and analysis, such as those used by ethics consultants, can help resolve questions about the standard of care. PMID- 3337487 TI - Recognition and management of expanding myocardial infarction. PMID- 3337488 TI - Empiric antibacterial therapy in granulocytopenia induced by cancer chemotherapy. PMID- 3337489 TI - Medical student education in clinical pharmacology and therapeutics. PMID- 3337490 TI - The changing adolescent. PMID- 3337491 TI - The future internist. The Task Force on the Future Internist, American Board of Internal Medicine. AB - The American Board of Internal Medicine report of the Task Force on the Future Internist argues that, although the basic principles that underlie the structure and organization of internal medicine remain appropriate, the role of the future internist will be affected by predictable economic and social forces. This changed role will require specified changes in the curriculum of internal medicine training programs and in the certification process. PMID- 3337492 TI - Cytogenetic abnormalities predict clinical outcome in non-Hodgkin lymphoma. AB - Tumor cytogenetic analysis was done for 68 patients with newly diagnosed non Hodgkin lymphoma, and recurring cytogenetic abnormalities were correlated with achievement of complete remission, duration of complete remission, and survival. Among all patients, the presence of normal metaphases in tumor material was associated with a higher complete remission rate and longer survival. However, the duration of complete remission did not correlate with the presence or absence of chromosomal changes. Among patients with follicular lymphomas, the presence of normal metaphases in the tumor material was again associated with a higher rate of complete remission and with longer survival. Patients with structural abnormalities of chromosome 17 had a shorter survival than patients without these abnormalities. Among the patients with diffuse large-cell and immunoblastic lymphomas, those with breaks in the short arm of chromosome 2 had a longer survival than those without these breaks. We conclude that chromosomal abnormalities are predictive of clinical outcome in malignant lymphoma. PMID- 3337494 TI - Improving medical education in therapeutics. Health and Public Policy Committee, American College of Physicians. PMID- 3337493 TI - Clinical competence in diagnostic endoscopic retrograde cholangiopancreatography. Health and Public Policy Committee, American College of Physicians. PMID- 3337495 TI - Essential hypertension in men and women. PMID- 3337496 TI - Cost containment and hypertension. PMID- 3337497 TI - Sex bias and coronary bypass surgery. PMID- 3337498 TI - Hazards of the Swan-Ganz catheter. PMID- 3337499 TI - Screening for primary hyperparathyroidism. PMID- 3337501 TI - Inability to predict diagnosis in febrile intravenous drug abusers. PMID- 3337500 TI - Plasmapheresis and pulse cyclophosphamide in systemic lupus erythematosus. PMID- 3337502 TI - Routine testing for chlamydial cervical infections. PMID- 3337503 TI - Cryptococcal bursitis. PMID- 3337504 TI - HIV-1 and HIV-2 double infection in Greece. PMID- 3337505 TI - Thrombotic thrombocytopenic purpura and herpes zoster infection. PMID- 3337506 TI - Classification systems for human immunodeficiency virus (HIV) infection. PMID- 3337507 TI - Evaluating the risk of gallbladder cancer. PMID- 3337508 TI - Meta-analysis in clinical research. PMID- 3337509 TI - Laboratory use: persisting attitudes implicit in a national examination. PMID- 3337510 TI - Standard and computed tomography in the evaluation of chest neoplasms. PMID- 3337511 TI - Renal salt wasting in patients treated with cisplatin. AB - Although cisplatin nephrotoxicity is well documented, renal sodium wasting has rarely been reported. Seven of seventy patients treated with cisplatin over 18 months developed salt-wasting nephropathy and orthostatic hypotension. All patients presented 2 to 4 months after starting cisplatin with severe orthostatic hypotension (mean orthostatic change in blood pressure, -37 +/- 8 mm Hg) without preceding extrarenal volume loss or diuretic use. Urinary sodium concentration was 85 to 145 mmol/L, fractional excretion of sodium was 1.0% to 8.0%, and urinary osmolar concentration was 340 to 619 mmol/kg, while orthostatic hypotension was present. Six patients were hyponatremic (116 to 137 mmol/L). Serum creatinine and urea levels were elevated in five patients but fell after rehydration. Vasopressin averaged 5.4 pg/mL (2.1 to 12.7 pg/mL) (n = 5) and was suppressed with hydration (mean, 2.5 pg/mL, 1.5 to 4.3 pg/mL). Plasma renin activity was undetectable in two patients and low in three patients, and aldosterone was low in six patients despite clinical volume depletion. Cisplatin may produce renal salt wasting causing symptomatic orthostatic hypotension and hyponatremia associated with abnormalities of the renin-aldosterone system. PMID- 3337512 TI - Seronegative Hashimoto thyroiditis with thyroid autoantibody production localized to the thyroid. AB - A patient without serologic evidence of an autoimmune disorder had a thyroidectomy for neck compression caused by her goiter. Histologic examination of the gland revealed pathologic changes compatible with Hashimoto disease, and lymphocytes isolated from her thyroid gland were transformed into lymphoblastoid cells in vitro by Epstein-Barr virus in the presence of cyclosporine. These cells produced antibodies against thyroglobulin, thyroid microsome, thyrocyte membrane, and thyrotropin, whereas lymphoblastoid cells produced from the patient's peripheral blood lymphocytes showed no antithyroid activity. Several human monoclonal antibodies were produced from the intrathyroidal lymphocytes by fusion with the SHM-D33 heteromyeloma, and the resulting cell lines produced antibodies with high-affinity binding specific for thyroid antigens. These studies show that lymphocytes capable of producing antithyroid antibodies can be present in the thyroid glands of patients with Hashimoto disease without evidence of a peripheral immune response, thus indicating that Hashimoto disease can exist as an organ-restricted autoimmune disorder. PMID- 3337514 TI - Fine-needle aspiration biopsy of patients with acquired immunodeficiency syndrome (AIDS): experience in an outpatient clinic. AB - One hundred twenty-one fine-needle aspiration biopsies of lymph nodes were done on 113 men followed in the AIDS (acquired immunodeficiency syndrome) Outpatient Clinic of the San Francisco General Hospital. The cytologic diagnoses on these 121 biopsies included 60 (50%) hyperplasias, 24 (20%) non-Hodgkin lymphomas, 21 (17%) mycobacterial infections, 12 (10%) cases of Kaposi sarcoma, and 1 each of Hodgkin disease, giant cell carcinoma, nasopharyngeal carcinoma, and squamous cell carcinoma. No false-positive results occurred in this series, but five false negative results were seen in the 10 patients with hyperplasia on fine-needle aspiration biopsy specimens who subsequently had open surgical biopsy. From our experience, we believe fine-needle aspiration biopsy is a useful, cost-effective initial method to evaluate lymphadenopathy in patients seen at an AIDS outpatient clinic. PMID- 3337513 TI - Gram-positive infections and the use of vancomycin in 550 episodes of fever and neutropenia. AB - STUDY OBJECTIVE: To determine the appropriate role for vancomycin in neutropenic patients with cancer. To review the incidence, types, and outcome of gram positive infections in a series of neutropenic patients with cancer. DESIGN: Retrospective review. SETTING: Inpatient units of the Medical and Pediatric Oncology Branches of the National Cancer Institute. PATIENTS: Five hundred and fifty consecutive episodes of fever and neutropenia in patients with cancer randomized prospectively on another study to receive either ceftazidime alone or combination antibiotics for initial empirical therapy. INTERVENTION: Intravenous vancomycin (dosage adjusted by serum levels). MEASUREMENTS AND MAIN RESULTS: Gram positive organisms were the commonest of the bacterial pathogens isolated (63%). Of the 53 gram-positive organisms accounting for primary infections (isolated at initial presentation), there were 36 staphylococcal isolates (19 coagulase negative and 17 coagulase-positive), 13 streptococcal isolates (8 non-group D and 5 group D), and 4 polymicrobial isolates. Of the 22 secondary gram-positive infections (occurring after institution of initial antibiotics), there were 10 streptococcal isolates (9 group D and 1 non-group D), 7 staphylococcal isolates (6 coagulase-negative and 1 coagulase-positive), and 5 polymicrobial isolates. Vancomycin was used to treat 26 of the 53 primary infections, but was begun only after knowledge of the isolate in 25. Vancomycin was used to treat 17 of the 22 secondary infections, and begun only after knowledge of the isolate in 14. This approach resulted in no treatment failures for the primary infections, and a single microbiological failure for the secondary infections. There was a tendency towards a greater proportion of secondary gram-positive infections in the monotherapy group compared to the combination therapy group (16 of 282 compared with 6 of 268 respectively, P2 = 0.04 by the chi-squared test); but all were treated successfully. CONCLUSION: Vancomycin need not be included in routine empirical therapy for febrile neutropenic patients, but should be added when clinical or microbiological data suggest the need. PMID- 3337515 TI - Intrathecal production of antibodies against Toxoplasma gondii in patients with toxoplasmic encephalitis and the acquired immunodeficiency syndrome (AIDS). AB - We attempted to determine whether patients with the acquired immunodeficiency syndrome (AIDS) and toxoplasmic encephalitis produce Toxoplasma antibodies in the central nervous system, and whether these antibodies would be useful for diagnosing toxoplasmic encephalitis. Thirty-seven patients with AIDS and toxoplasmic encephalitis and 11 patients with AIDS alone were studied. All patients had serum IgG but not IgM Toxoplasma antibodies. Twenty-three of the patients with AIDS and toxoplasmic encephalitis had Toxoplasma antibody in cerebrospinal fluid compared to none of the patients with AIDS alone. Of the patients with AIDS alone who had serum antibodies to T. gondii, none had Toxoplasma antibodies in cerebrospinal fluid. Production of antibodies in the central nervous system was seen in 11 of 16 patients with AIDS and toxoplasmic encephalitis but not in 4 patients in the control group who only had Toxoplasma antibody in their cerebrospinal fluid. These results suggest that production of T. gondii antibodies in the central nervous system may be diagnostic of toxoplasmic encephalitis. PMID- 3337518 TI - 1-Desamino-8-D-arginine vasopressin (desmopressin) shortens the bleeding time in storage pool deficiency. PMID- 3337517 TI - Dichloroacetate in the treatment of lactic acidosis. AB - An open, prospective evaluation of the effects of dichloroacetate on morbidity and survival time was done in 29 pediatric and adult patients with lactic acidosis. Dichloroacetate was administered intravenously over 30 minutes as two 50 mg/kg body weight doses separated by 2 hours. Five patients underwent retreatment with two additional drug doses and were considered new cases when analyzing for treatment response. Survival, however, was determined from the time of initial entry into the study. Patients were considered to respond to treatment if arterial lactate concentration decreased at least 20% from the pretreatment level within 6 hours of beginning the first dichloroacetate infusion. Using this criterion, 26 cases responded to therapy with dichloroacetate. For all cases, patients' mean arterial lactate concentration decreased 52% (P = 0.0009), arterial bicarbonate concentration increased 35% (P = 0.0003), and arterial pH increased (P = 0.024) to normal, defined as the range 7.35 to 7.45. Among responders, however, arterial lactate concentration decreased 74% (P = 0.0001), arterial bicarbonate level increased 47% (P = 0.0001), and arterial pH increased (P = 0.0004) to the normal range. Median survival time among responders was 60 hours, compared to 26 hours among nonresponders (P less than 0.001). There was no evidence of toxicity to dichloroacetate. PMID- 3337516 TI - Human immunodeficiency virus and hepatitis delta virus in homosexual men. A study of four cohorts. AB - The prevalence of hepatitis delta virus antibodies was determined in four cohorts of homosexual or bisexual men positive for hepatitis B surface antigen who were evaluated between April 1984 and April 1985. Antibodies to hepatitis delta virus were found in 16 of 106 men in Los Angeles (15.1%; 95% confidence interval [Cl], 8.3% to 21.9%); 6 of 64 men in San Francisco (9.4%; 95% Cl, 3.5% to 19.3%); 1 of 76 men in Pittsburgh (1.3%; 95% Cl, 0.03% to 7.1%); and 0 of 52 men in Chicago (0%; 95% Cl, 0% to 5.6%). From 44.0% to 65.4% of men negative for hepatitis delta virus and all men positive for hepatitis delta virus but one (P less than 0.0001) were positive for antibodies to human immunodeficiency virus (HIV). In multivariate analysis, infection with hepatitis delta virus was associated with intravenous drug use (adjusted odds ratio [OR] = 6.7, P less than 0.01), with sexual activity as measured by number of partners (adjusted OR = 8.4, p less than 0.01), and probably with rectal trauma (adjusted OR = 3.9, P = 0.17). As with HIV infection, prevalence of hepatitis delta virus infection in homosexual men differs by location and is most likely transmitted both sexually and parenterally. PMID- 3337519 TI - Metoprolol-induced hepatitis: rechallenge and drug oxidation phenotyping. PMID- 3337520 TI - Amiodarone-induced delirium. PMID- 3337522 TI - [Intra-arterial chemotherapy of ovarian cancer using a subcutaneously embedded reservoir--a case showing remarkable response to intermittently repeated low-dose intra-arterial infusion chemotherapy]. AB - By fitting a subcutaneously embedded reservoir to an aged patient with ovarian cancer in whom exploratory laparotomy was performed, we attempted intermittent intraarterial infusion chemotherapy using small doses of CDDP and ADM, and obtained favorable results. The catheter was inserted at an artery in the lower abdominal wall, attached at the site where the pointed end reached the upper margin of L3, and fixed to the fascia recta, connecting with the reservoir on the reverse side. As drug solutions, 5 mg of CDDP and 5 mg of ADM were transcutaneously infused twice per week. Results 1) A marked necrotic tendency was noted in the tumor, and retention of ascites was remarkably decreased. 2) Hardly any nausea and vomiting as side effects were noted, and decreases in leucocyte and platelet counts were mild, recovering rapidly due to dropout. 3) Anxiety regarding infection was minimal at times other than when the drug solution was being infused, and patient was able to take a bath. From the above mentioned results, it was considered that maintenance chemotherapy on an outpatient basis using approximately one dose per week would be possible in the future for ovarian cancer. PMID- 3337521 TI - [Augmentation of murine organ-associated natural immune responses by cepharanthin]. AB - Oral administration of cepharanthin (bisbenzylisoquinoline alkaloid) to mice was effective in the organ-associated immune responses. Cepharanthin, as a biological response modifier (BRM), augmented natural killer (NK) activity of leukocytes isolated from the spleen, lymph node, lung, and liver. The degree of NK augmentation was almost the same in these organs without lymph node, and reached to the maximum levels 3 days after cepharanthin administration. In addition, adherent leukocytes (greater than 95% macrophages) isolated from the lung or liver following cepharanthin administration also exhibited an augmented macrophage-mediated cytotoxicity. These results suggest that such organ associated immune responses may play an important role in the antitumor and/or antimetastatic effects mediated by cepharanthin. PMID- 3337523 TI - [Changes in the surgical treatment of breast cancer]. AB - The principle in surgery for breast cancer is to clean out and remove en masse the primary lesion within the breast as well as the lymph nodes (metastases) in the vicinity. This fundamental approach to surgical intervention was established by Halsted and Meyer at the close of the nineteenth century. This has been termed typical mastectomy to this day and standard radical mastectomy has been the method used. Later, a more expanded type of radical surgery was performed on somewhat more advanced cases, but a less radical approach then came about. Since 1960, the excision of nodes in the cerebrum and cerebellum was not used for early cancer, and in some cases a more conservative approach in which only part of the breasts was removed resulted, as Europe and the United States were heavily toward reduced operations. Thus, it was considered that axillary expurgation was needed, but that excision of nodes in the cerebrum and cerebellum was not essential in every case. One approach is less aggressive, whether as to the expurgation or excision of the surrounding area of the breast; in certain cases, treatment may be combined with radiation and the surgery minimized. The above-mentioned operative procedure which leaves brain nodes intact has been called modified radical mastectomy. This is subdivided into the Auchincloss method, in which modes in the cerebellum are extirpated, and the Patey method, in which the cerebral nodes are preserved. In Japan this approach has been used for breast cancer in Stage I and Stage II, with surgery gradually becoming the mainstream. Conservative breast operation procedures such as tumor extirpation, partial breast removal or segmental resection are still rare in Japan but very common in Europe and the United States. Since remote metastases frequently occur through the circulation in breast cancer, in recent years it has generally been regarded as a whole-body disease and, in terms of the advance of the cancer in each case, the method of surgery is selected. There is a strong tendency to combine surgery with other methods (radiation, chemotherapy, hormonal therapy). PMID- 3337524 TI - [Remarkable effect of vindesine sulfate (VDS) in the treatment of metachronous lung metastasis of esophageal cancer--a case report]. AB - A case of metachronous lung metastasis treated by intravenous administration of VDS after esophageal cancer surgery is reported. A 63-year-old man who had undergone intrathoracic esophagectomy for cancer of the esophagus was shown to have a coin lesion in the middle lobe of the right lung on X-ray examination about one year after surgery. The schedule for intravenous administration of VDS was 5 mg/body every week. The metastatic lesion disappeared after a series VDS administrations totalling 35 mg. Major side effects such as leukopenia and fever were occasionally observed during the course of drug administration. The patient required three occasions of hospitalization for these adverse effects. It is thus emphasized that an effect of VDS may be expected for hematogenous dissemination of esophageal cancer. PMID- 3337525 TI - [Roferon-A. Canferon-A. Interferon alpha-2A (genetic recombination)]. PMID- 3337526 TI - [Chronological trends in gastric cancer surgery in Japan]. AB - The development of surgery for gastric cancer in Japan was reviewed. Recently, favorable long-term results have been obtained in surgically treated gastric cancer patients. This success has been mainly attributable to the performance of extended lymph node removal since the 1960s and of active total gastrectomy since the 1950s. Furthermore, gastrectomy combined with the resection of other organs since the 1960s, has resulted in an improvement of resectability. On the other hand, modified lymph node removal for early gastric cancer has been promoted in the 1980s. With the progress of anticancer chemotherapy since the 1970s, the concept of reduction surgery has been introduced into cancer surgery, and active palliative gastrectomy has been performed. Despite the advances made in gastric cancer surgery, however, there is a definite limit to the surgical treatment of gastric cancer. For this reason, multidisciplinary therapy combined with surgery should be considered. PMID- 3337527 TI - [Changes in the surgical treatment of esophageal cancer]. AB - The surgical treatment of esophageal cancer has improved considerably during the past 50 years, and the operative mortality rate has become less than 5%. Indications for surgery have been extended and the postoperative outcome has improved to give a 5-year survival rate of 25% through combined use of radiation and chemotherapy. Recently, extended surgery with lymphadenectomy of the neck, thorax and abdomen has become widely performed. As a result, the recurrence rate in nodes has decreased, while that in organs has increased. It is thus important to establish a suitable form of chemotherapy as well as achieving early detection of cancer. PMID- 3337528 TI - [Development of the surgical therapy of malignant liver tumors]. AB - The development of surgical treatment for malignant liver tumor was reviewed. The developmental process can apparently be divided into four periods. The first period up to 1968 is when surgical trials for liver tumors were started, and much effort was directed toward the establishment of systematic procedures for hepatic resection. The second period starts form 1968, when the Liver Cancer Study Group of Japan was inaugurated to organize investigators participating in the treatment of, and basic research on liver tumors. During this period, the basis for contemporary surgical treatment and sophisticated means of diagnosis such as such as determination of serum AFP level, selective angiography, and liver scintigraphy were established. This period came to an end around 1977 when computed tomography and ultrasonography were developed and popularized. In the third period, a variety of procedures for hepatic resection such as lobectomy, segmentectomy and newly devised echo-guided sub-segmentectomy were performed, based on the close evaluation of hepatic functional reserve. However, analysis of the outcome in patients who had undergone surgery alone suggested the limitations of surgical treatment, leading to the advent of the 4th period two to three years ago. The strategy of therapy in the 4th period has been aimed at multidisciplinary treatment such as transarterial embolization, intratumoral injection of tumoricidal agents, radiotherapy, regional chemotherapy and immunotherapy. PMID- 3337529 TI - [Two-route chemotherapy by CDDP and STS in liver metastasis of gastrointestinal adenocarcinoma]. AB - Nine (six male and three female) patients with unresectable liver metastasis of gastrointestinal adenocarcinoma were treated by two-route chemotherapy using cis diamminedichloroplatinum (CDDP) and sodium thiosulfate (STS). Of the nine patients, two had colon cancer, three had stomach cancer and the remaining four gall bladder cancer. In these patients, 100 mg/body of CDDP was administered through the common hepatic artery by the balloon-occluded arterial infusion (B.O.A.I.) method, and just after administration, intravenous infusion of STS (10 g/body) was given. The treatment was repeated at intervals of six to 12 weeks, and the following results were obtained: 1) Seven patients of the nine were eligible for evaluation of response to the treatment. Of the seven cases, partial response (PR) was recorded in two cases, and no change (NC) in five. The response rate in eligible cases was about 30%. 2) Though all the patients suffered nausea and vomiting to a mild degree after the treatment, none of the patients showed significant side effects potentially limiting the dose, such as bone marrow suppression and/or renal failure. In conclusion, this study demonstrated the efficacy of CDDP for liver metastasis of gastrointestinal adenocarcinoma, and the protective effects of STS against the toxicity of CDDP were well indicated, in spite of the low number of cases examined. PMID- 3337530 TI - [A six-day subrenal capsule assay for predictive testing of primary human tumors]. AB - We carried out a total of 36 in vivo chemosensitivity tests in 33 cases of human malignant tumor using the subrenal capsule assay, developed by A.E. Bogden et al. Of the 36 assays, 31 were evaluable. The chemosensitivity of each tumor varied individually. UFT, 5-fluorouracil, mitomycin-C and adriamycin were administered to gastrointestinal cancer patients regularly, but our SRC-assay showed a high sensitivity rate for UFT and 5-fluorouracil but a low sensitivity rate for mitomycin-C and adriamycin. Nine patients had clinically evaluable lesions and a correlation between the assay results and clinical response existed in 6 cases. The true positive rate was 50% (3/6), the true negative rate 100% (3/3), and the overall predictive accuracy 66% (6/9). This study suggested that 6-day SRC assay is useful for selecting effective anti-tumor agents for the treatment of cancer patients. PMID- 3337531 TI - [Influence of a fosfomycin combination on the anti-tumor effect of CDDP]. AB - To elucidate the influence of fosfomycin (FOM) on the anti-cancer effect of cisplatin (CDDP), experimental chemotherapy of CDDP with or without FOM was performed. A human lung cancer cell line, HLC-1 serially transplanted into nude mice was treated with CDDP 10 mg/kg (i.p.). Tumor doubling time in CDDP group and CDDP + FOM group are 26.78 +/- 6.3 days and 33.90 +/- 11.82 days respectively, and they are significantly elongated compared to control group. Serum NAG level in CDDP + FOM group was significantly lowered. Therefore, we concluded that anti tumor effect of CDDP was not diminished by FOM combination. PMID- 3337532 TI - Cutaneous manifestations of acrodynia (pink disease). AB - A 14-month-old girl who presented with multiple systemic complaints was found to have gingivitis, peeling of her palms and soles, and a peculiar acral eruption. A diagnosis of acrodynia, or pink disease, was confirmed by elevated levels of mercury in the urine. The many cutaneous manifestations of this once common disease are discussed. PMID- 3337533 TI - Development of neuroendocrine (Merkel cell) carcinoma mixed with squamous cell carcinoma in erythema ab igne. AB - Squamous cell carcinoma and neuroendocrine (Merkel cell) carcinoma are cutaneous neoplasms that have only occasionally been reported to coexist. Squamous cell carcinoma, but not neuroendocrine (Merkel cell) carcinoma, is a rare complication of erythema ab igne. This report describes the development of both neoplasms arising within the same tumor mass in an area of erythema ab igne. PMID- 3337534 TI - Acquired dyskeratotic leukoplakia. AB - A 36-year-old woman developed progressive dyskeratotic leukoplakia of the palate, lips, attached gingiva, and labial surfaces of the genitalia. On microscopic examination, clusters of dyskeratotic cells were found throughout the epithelium, except in the basal cell layer. The clinical and histologic differential diagnosis included candidiasis, oral hairy leukoplakia, lichen planus, condyloma acuminatum, Darier's disease, hereditary benign intraepithelial dyskeratosis, and white sponge nevus. Her clinical and histologic findings do not permit classification into any of these well-recognized entities. PMID- 3337535 TI - Subcutaneous nodules in a man diagnosed as having tuberculosis. Disseminated actinomycosis. PMID- 3337536 TI - Free drug samples. Use and abuse. PMID- 3337538 TI - Undermining subcutaneous island flaps. PMID- 3337537 TI - Yellow staining of skin among plastics workers. PMID- 3337539 TI - Kaposi's sarcoma responsive to interferon therapy. PMID- 3337540 TI - Keratitis, ichthyosis, and deafness (KID) syndrome: suggested changes in terminology. PMID- 3337541 TI - Solar purpura. PMID- 3337542 TI - Maternal pemphigus foliaceus with cell surface antibody bound in neonatal epidermis. PMID- 3337543 TI - Persistent cutaneous reaction to intramuscular vitamin K injection. PMID- 3337544 TI - Progressive, persistent, hyperkeratotic lesions in incontinentia pigmenti. PMID- 3337546 TI - A histological study of the evolution of solar urticaria. AB - The histological evolution of solar simulator-induced lesions of solar urticaria was investigated in four severely affected white patients. A series of two to 32 minimal whealing doses of radiation, each much lower than the 24-hour minimal erythema dose, was administered to separate buttock sites. Biopsy specimens were obtained from the exposed areas at five minutes and two and 24 hours later, as well as from adjacent nonexposed skin. Lesions showed a statistically significant dose-dependent increase, predominantly perivascular, in upper dermal neutrophil and eosinophil numbers at five minutes and two hours, but not at 24 hours, and at higher radiation doses in mononuclear cell numbers by 24 hours. Nonirradiated patient skin and irradiated control subject skin was not similarly affected. These changes may be associated with the pathogenesis of solar urticaria. PMID- 3337545 TI - Postphlebitic localized hypertrichosis. PMID- 3337547 TI - Aquagenic pruritus. Water-induced activation of acetylcholinesterase. AB - Four patients with aquagenic pruritus (AP), one patient with polycythemia rubra vera, one patient with cold urticaria, and three normal control volunteers were studied to better understand the pathophysiology of water-induced itching. Punch biopsy specimens were taken before and after water contact; the specimens were immediately frozen, sectioned, and stained histochemically for acetylcholinesterase (AChE) activity. This was localized in the nerve fibers surrounding eccrine sweat glands and was quantified by microspectrophotometry. In AP and polycythemia rubra vera after water exposure a significantly increased AChE activity suggesting acetylcholine release was observed, whereas in the patient with cold urticaria and the controls, a significant decrease was noted. Two related patients with AP had an inherited abnormality of serum cholinesterase, which, however, had no obvious correlation with their particular disease. The proof of AChE activation might support the clinical diagnosis and indicate a hypothetical involvement of eccrine sweat glands in the pathogenesis of AP. PMID- 3337548 TI - Werner's syndrome. Evidence for preferential regional expression of a generalized mesenchymal cell defect. AB - We describe a patient with Werner's syndrome from whom skin biopsy specimens were sampled for histology and electron microscopy and fibroblasts were cultured. Tissue sampled from five sites that varied in clinical presentation revealed striking changes in the dermoepidermal junction, elastic fibers of the papillary and reticular dermis, and adipose tissue of the hypodermis. The density and organization of the collagenous connective tissue was altered variably depending on the biopsy site. Changes noted in the epidermis were indicative of tissue regeneration and repair. Cells derived from acral areas grew poorly and could not be passed. Collagen synthesis in these cells was enhanced approximately 50%, and collagenase expression was decreased to a similar degree. Cells derived from the skin of the trunk could be passed but had an abbreviated in vitro life span. Collagen synthesis in these cells was unaltered. Serum from the patient with Werner's syndrome or from his obligate heterozygote offspring stimulated collagen synthesis in low-passage normal human skin fibroblast target cells. Sequential passage of these normal cells resulted in a blunting of the stimulatory effect. These observations suggest that a stimulator of collagen synthesis exists in the serum of patients with Werner's syndrome and that as cells (either normal or Werner's syndrome) "age" in vitro they may become hyporesponsive to this as yet undefined stimulatory factor in serum. PMID- 3337549 TI - Polynuclear aromatic hydrocarbon and heavy metal concentrations in sediments at coastal South Carolina marinas. PMID- 3337550 TI - Differences in the effects of mercury on telson regeneration in two populations of the grass shrimp Palaemonetes pugio. PMID- 3337551 TI - Lead poisoning in six captive avian species. PMID- 3337552 TI - Acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to mink. PMID- 3337554 TI - Fate and metabolism of dichlorprop in cereals and field grass. PMID- 3337553 TI - Influence of termite treatment in the home on the chlordane concentration in human milk. PMID- 3337555 TI - Carbamate insecticide removal in laundering from cotton and polyester fabrics. PMID- 3337556 TI - Short-term lethality and sediment avoidance assays with endrin-contaminated sediment and two oligochaetes from Lake Michigan. PMID- 3337557 TI - The Kaplan and Meier and the Nelson estimate for the probability of ulcer recurrence 10 and 15 years after parietal cell vagotomy. AB - The use of a nonparametric estimate from incomplete observations is demonstrated on ulcer recurrence 10-15 years after parietal cell vagotomy in 339 patients with duodenal ulcer. The median period of observation was 108 months (range: 1-197 months). Proven recurrent ulcer developed in 62 patients. The life-table method as described by Kaplan and Meier and Nelson's modification are demonstrated. The calculated risk of recurrence after 10 years was 23% (+/- 3.8%) and after 15 years was 27% (+/- 4.3%). The rate of recurrence seemed to decline toward the end of the trial time. PMID- 3337558 TI - Treatment of dermatofibrosarcoma protuberans with Mohs micrographic surgery. AB - Ten patients with dermatofibrosarcoma protuberans, all of whom had been treated previously by conventional excisional surgery without success, were treated with Mohs micrographic surgery. A team approach utilizing margin control by Mohs trained physicians and reconstruction by surgical specialists was employed. Average follow-up exceeds 3 1/2 years, with no recurrences. Microscopically controlled excision appears to be the treatment of choice for dermatofibrosarcoma protuberans. PMID- 3337559 TI - Partial biliary obstruction caused by chronic pancreatitis. An appraisal of indications for surgical biliary drainage. AB - This paper presents a retrospective review of 38 patients with intrapancreatic bile duct strictures secondary to chronic alcoholic pancreatitis. The strictures were identified by endoscopic retrograde cholangiopancreatography (ERCP). All patients with pancreatic cancer and gallstone pancreatitis were excluded. The mean alkaline phosphatase and total bilirubin values were 344 +/- 57 IU/dl and 4.4 +/- 0.7 mg/dl, respectively. The mean stricture length was 3.9 +/- 0.5 cm, and the mean common bile duct (CBD) diameter was 1.8 +/- 0.2 cm. The degree of bilirubin and alkaline phosphatase elevation did not correlate with stricture length or the severity of bile duct dilatation. Eighteen of the 38 patients received surgical biliary drainage (BD) as part of their initial therapy, and 20 patients did not. Liver function tests, intrapancreatic stricture length, and the degree of proximal CBD dilation were comparable in these two groups. Patients not undergoing BD did well clinically as only one patient required BD over an average follow-up period of 3.8 years. In conclusion, bypass of these strictures is usually unnecessary, and most patients may be safely treated without operation. PMID- 3337560 TI - Operative treatment of Crohn's ileocolitis complicated by ileosigmoid and ileovesical fistulae. AB - Ileovesical and ileosigmoid fistulae were found to coexist in 22 patients with Crohn's ileocolitis. Persistent or recurrent urinary tract infection was a complaint in all cases, and 11 patients reported pneumaturia and/or fecaluria. Thus, bladder involvement was either suspected or clinically apparent in each patient. The cystogram was the best confirmatory test for the ileovesical fistula (positive in 9 of 22 patients). The coexistence of the sigmoid fistula was best diagnosed on intestinal radiographs (positive in 9 of 22 patients); there were no clinical signs of its presence. The coexistence of ileosigmoid and ileovesical fistulae was the sole indication for operation in two patients. In all others, a combination of factors required surgical therapy. An ileocolonic resection with primary intestinal anastomosis was performed in 16 patients and exteriorization was performed in six patients. The sigmoid defect was closed primarily in 16 patients and required wedge resection in the other six patients. The bladder defect was sparingly excised and closed with absorbable sutures. All patients recuperated without anastomotic leaks, bladder leaks, or persistent cystitis. This experience indicates that coexisting ileosigmoid and ileovesical fistulae may add complexity to an ileocolonic resection for Crohn's disease, but is not a difficult management problem for the gastrointestinal surgeon. PMID- 3337561 TI - Intraoperative and external beam irradiation for locally advanced colorectal cancer. AB - In view of poor local control rates obtained with standard treatment, intraoperative radiation (IORT) using electrons was combined with external beam irradiation and surgical resection, with or without 5-fluorouracil (5FU), in 51 patients with locally advanced colorectal cancer (recurrent, 36 patients; primary, 15 patients). Patients received 4500-5500 cGy (rad) of fractionated, multiple field external beam irradiation and an IORT dose of 1000-2000 cGy. Thirty of 51 patients (59%) are alive and 22 patients (43%) are free of disease. In 44 patients at risk greater than or equal to 1 year, local progression within the IORT field has occurred in 1 of 44 (2%) and within the external beam field in 8 of 44 (18%). All local failures have occurred in patients with recurrence or with gross residual after partial resection, and the risk was less in patients who received 5FU during external irradiation (1 of 11, 9% vs. 6 of 31, 19%). The incidence of distant metastases is high in patients with recurrence, but subsequent peritoneal failures are infrequent. Acute and chronic tolerance have been acceptable, but peripheral nerve appears to be a dose-limiting structure. Randomized trials are needed to determine whether potential gains with IORT are real. PMID- 3337563 TI - Colorectal villous and tubulovillous adenomas equal to or greater than four centimeters. AB - The records of 237 patients treated for benign and malignant villous and tubulovillous adenomas at Roswell Park Memorial Institute from 1963 to 1987 were reviewed. Sixty-five adenomas were greater than or equal to 4 cm and form the basis of this report. Fifteen (23%) were in the cecum, 3 (5%) in the right colon, 1 (1%) in the splenic flexure, 10 (15%) in the sigmoid colon, and 36 (55%) in the rectum. The most common symptoms were rectal bleeding (70%), mucus diarrhea (44%), constipation (22%), and tenesmus (19%). Fifty-five (85%) of these large adenomas contained invasive adenocarcinoma and one in situ carcinoma. Two thirds of invasive carcinomas arose from predominantly villous adenomas and one third from tubulovillous adenomas. Half of all malignant adenomas demonstrated metastases to regional lymph nodes or distant metastases. Seven malignant adenomas (12%) were associated with synchronous adenocarcinomas of the colon, and 29% of malignant adenomas were associated with synchronous adenomatous polyps, principally tubular type. Four of nine benign, large adenomas were associated with synchronous adenomas but with no adenocarcinomas. No relationship was found between the size of the adenoma, location, or Dukes' stage. Though the incidence of in situ and invasive carcinomas is clearly related to the size of the adenoma, a linear relationship could not be demonstrated. PMID- 3337562 TI - Functional and oncologic results after coloanal anastomosis for low rectal carcinoma. AB - Thirty-five patients who had adenocarcinoma of the middle third of the rectum were treated by resection and coloanal anastomosis. The aim of this study was to assess functional and oncologic results of an original technique of coloanal anastomosis. There was no operative mortality, and operative morbidity consisted of seven anastomotic leaks with two failures. Among 31 patients assessed for functional results only one had unsatisfactory results. Good continence was obtained within a few weeks for the 30 patients who had satisfactory results. No patients were lost to follow-up, which was over 5 years in 24 patients (68%). The 5-year survival rate was 64%, identical to that for other series. PMID- 3337565 TI - The management of penetrating injuries of the back. A prospective study of 230 patients. AB - This is a prospective study of 230 patients with penetrating injuries of the back. The decision to operate or observe was taken exclusively on the abdominal physical findings. One hundred ninety-five patients (85%) did not require operation, 30 (13%) underwent a therapeutic laparotomy, four (1.7%) an unnecessary operation, and one patient (0.4%) had a completely negative laparotomy. The diagnosis and management was delayed in five (2.2%) patients with no serious consequences. Mortality rates were not recorded in this series. The initial physical examination was accurate in 95.2% of the patients. We suggest that penetrating injuries of the back should be assessed in the same way as anterior abdominal injuries. Physical abdominal examination is reliable in detecting significant intra-abdominal injuries. PMID- 3337564 TI - Postoperative complications and mortality after surgery for gastric cancer. AB - Complication rates and postoperative mortality were studied in 1010 consecutive patients entered into the Norwegian Stomach Cancer Trial. Twenty-eight per cent of the patients had one or more complications (31% of the men and 21% of the women). General complications (pneumonia, thromboembolic, and cardiac) were most frequent. The postoperative mortality rate for resected patients was 8.3% (63 of 763). Complication and mortality rates were highest for proximal resections (52% and 16%) followed by total gastrectomy (38% and 8%), subtotal resection (28% and 10%), and distal resection (19% and 7%). By logistic regression analysis it was found that age, sex, operative procedure, prophylactic antibiotics, and splenectomy were significantly related to postoperative complications. The odds ratio for complication for men versus women was 1.75: for no antibiotics versus antibiotic prophylaxis it was 2.5. Relative to distal resection the odds ratio for complications after subtotal resection was 2.2, for total gastrectomy was 3.9, and for proximal resection was 7.6. Age and sex were the only factors that affected operative mortality. The odds ratio for mortality for men versus women was 2.3. The odds ratio for operative mortality was 2.2 when the age of the patient increased with 10 years. PMID- 3337566 TI - Relationship of estrogen and progesterone receptors to prognosis in breast cancer. AB - To ascertain the role of estrogen (ER) and progesterone (PR) receptors as prognostic indicators of resectable breast cancer, the records of 204 patients were analyzed whose receptor studies were done at the Maimonides Medical Center from 1975 to 1983. All patients had radical or modified radical mastectomies and did not show any evidence of distant metastases at the time of operation. Median follow-up was 37 months. An additional 117 patients received some form of adjuvant therapy, mainly chemotherapy, and were analyzed separately. Life table analysis using the log rank test for measuring significance, and a Cox multivariate analysis was performed. At 48 months, 22% of the ER positive (ER+) group versus 33% of the ER negative (ER-) group had recurred as compared to 16% and 35% for the PR+ versus PR- groups, respectively. Life table analysis of the disease free interval (DFI) showed that the difference between the ER+ and ER- groups was not significant (p greater than 0.1), while the difference in DFI between the PR+ and PR- groups was significant (p less than 0.05). Multivariate analysis revealed that the most important factors in predicting the DFI were nodal status (p less than 0.001), tumor size (p less than 0.025), and progesterone receptor status (p less than 0.05). Estrogen receptor status was not found to be significant. In conclusion, PR- patients have a shorter DFI than PR+ patients and that PR status is a more valuable predictor of DFI than ER status. PMID- 3337568 TI - An enclosed system for continuous postoperative mediastinal aspiration. AB - Blockage of mediastinal drainage tubes in the postoperative cardiac surgical patient can result in tamponade, and the small child, with a necessarily small drainage tube, is particularly susceptible to instability arising from accumulating blood in the mediastinum. A system for continuous evacuation of blood in drainage tubes is described that decreases the likelihood of blocked tubes and resultant tamponade. PMID- 3337567 TI - Bronchobiliary fistulas in adults. AB - Reported herein are 16 cases of nontraumatic bronchobiliary fistula in adults observed over 32 years. The fistulas were due to either biliary obstruction or infectious diseases involving the liver. All patients had biloptysis and other respiratory symptoms, and most had cholangitis, jaundice, and/or sepsis. The diagnosis was established by fistulography or cholangiography. All patients except one were treated surgically by relief of biliary obstruction and drainage of intra-abdominal abscesses. All 15 surgically treated patients had a successful outcome. Rapid diagnosis and early treatment of septic complications are necessary, but careful assessment and surgical relief of the biliary obstruction are essential in successfully treating this condition. PMID- 3337569 TI - A groove on a probe for coronary anastomosis. PMID- 3337570 TI - Venous cannula for cardiopulmonary bypass. PMID- 3337571 TI - Obstruction to left coronary artery blood flow secondary to obliteration of the coronary ostium in supravalvular aortic stenosis. AB - Supravalvular aortic stenosis is characterized by obstruction of the left ventricular outflow tract distal to the aortic valve, and may result in diminished coronary artery blood flow. This report describes the cases of 2 patients in whom obstruction to left coronary artery flow was caused by obliteration of the coronary ostium itself. This mechanism differs from the more commonly recognized cause--valve leaflet adhesion to the obstructing ridge of aortic tissue. The coronary artery obstruction found in these 2 patients required direct enlargement of the left coronary ostium in both. This mechanism of impaired coronary artery flow deserves emphasis, as traditional methods of extended patch aortoplasty may fail to relieve the coronary ostial narrowing. PMID- 3337572 TI - Mitral valve replacement with preservation of chordae tendineae and papillary muscles. AB - An operative technique for mitral valve replacement (MVR) with preservation of the chordae tendineae to the anterior leaflet as well as the posterior leaflet is reported. This technique consists of the division of the anterior leaflet into anterior and posterior segments, the shifting and reattachment of the divided segments to the mitral ring of the respective commissural areas, and the use of a low-profile bileaflet prosthetic valve. A comparison of left ventricular function data between patients having operation with this technique and those having operation with the conventional method of MVR revealed significantly better improvement in cardiac index (p less than 0.06), left ventricular end-systolic volume index (p less than 0.05), and left ventricular ejection fraction (p less than 0.10) in the former group. Left ventricular wall motion improved in the anterolateral (p less than 0.01) and apical areas (p less than 0.02) in patients operated on with our technique. Maintenance of continuity between the mitral annulus and papillary muscles is expected to have a beneficial effect on postoperative left ventricular performance in spite of increased afterload. PMID- 3337573 TI - Acquired immunodeficiency syndrome and the thoracic surgeon. PMID- 3337574 TI - Influence of preoperative showers on staphylococcal skin colonization: a comparative trial of antiseptic skin cleansers. AB - We undertook a prospective randomized observer-blinded study comparing the ability of preoperative showers with chlorhexidine gluconate (Hibiclens), povidone-iodine (Betadine), and a lotion soap (Safe 'N Sure) to diminish the staphylococcal skin flora of patients. By block randomization, patients scheduled for an elective cardiac operation or coronary artery angioplasty were assigned to shower with one of the study skin cleansers either once (evening only) or twice (both evening and morning) before the procedure. Semiquantitative samples for culture were obtained from the subclavian and inguinal sites on the evening before the procedure (baseline culture) and again the next morning before the operation. The chlorhexidine skin cleanser consistently reduced staphylococcal colony counts at both the subclavian and inguinal sites before the procedure. This reduction was significant for patients showering both evening and morning (p less than 0.05). The use of the povidone-iodine skin cleanser inconsistently affected skin flora. Patients using lotion soap either experienced no change or had an increase in colony counts. Chlorhexidine is more effective than povidone iodine in diminishing skin colonization with staphylococci in patients before operation. Repeated applications of chlorhexidine are superior to a single shower with this agent. PMID- 3337575 TI - Indwelling transbronchial catheter drainage of pulmonary abscess. AB - Adequate cavitary drainage is of paramount importance in the treatment of pulmonary abscesses. Occasionally this cannot be achieved despite vigorous chest physical therapy and the utilization of bronchoscopy. Intermittent transbronchial catheterization under fluoroscopic guidance has been suggested as a method to facilitate drainage. We have modified this technique by placing an indwelling intracavitary catheter, which allows irrigation and drainage over a prolonged period. This report describes this technique and our experience with 3 patients managed in this fashion. PMID- 3337576 TI - Aortico-left ventricular tunnel and aortic insufficiency. PMID- 3337577 TI - Inotropic effect of triiodothyronine following myocardial ischemia and cardiopulmonary bypass: an experimental study in pigs. AB - A significant reduction (p less than 0.0001) in plasma-free triiodothyronine (T3), which is known to have an inotropic effect, has been documented in patients undergoing open-heart procedures. To investigate the effect of this observation, 22 pigs underwent 2 hours (Group 1, r = 10) or 3 hours (Group 2, r = 12) of myocardial ischemia during cardiopulmonary bypass (CPB) at 26 degrees C; the myocardium was protected by cardioplegic solution and cold saline solution at 30 minute intervals. After the pig was rewarmed to 37 degrees C, CPB was discontinued, and measurements of hemodynamic function were made 10 and 70 minutes later. Half of the pigs (Subgroup B) received 6 micrograms of T3 intravenously immediately after removal of the aortic cross-clamp; the remainder (Subgroup A) received no T3. After 2 hours of ischemia, untreated pigs showed significantly reduced myocardial function 10 minutes after discontinuation of CPB. By 70 minutes after the end of CPB, 2 of 5 untreated pigs (Subgroup A) had died of low cardiac output, but all 5 treated pigs (Subgroup B) survived. After 3 hours of ischemia, both groups showed some reduced function at 10 minutes, though the reduction was more marked in untreated animals. By 70 minutes, 4 of 6 untreated pigs had died of myocardial failure and all treated pigs remained alive (p less than 0.03). Surviving pigs in both groups still demonstrated some reduced function compared with values obtained before CPB. When all pigs are considered together, overall survival of those that did not receive T3 was significantly less than those that did (p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3337578 TI - Cardiac valve replacement in children: a twenty-year series. AB - Ninety-four children ranging from 3 months to 19 years of age underwent cardiac valve replacement at Columbia Presbyterian Medical Center from 1965 to 1985. The overall operative mortality was 12%, but mortality was higher among patients less than 2 years of age, patients who had had previous cardiac operations, and patients requiring double-valve replacement. Seven of 11 patients who received mechanical valves and no anticoagulation experienced major thromboembolic events. An episode of gastrointestinal hemorrhage that was easily controlled represents the only bleeding complication in the entire series. Valve replacement in children continues to be a high-risk procedure, and efforts to preserve native valve function should be attempted when technically feasible. Our data also suggest that anticoagulation can be safely accomplished in the pediatric age group and should be employed in patients requiring placement of a mechanical prosthesis, especially in the mitral position. PMID- 3337579 TI - Incidence of primary tissue valve failure in porcine bioprosthetic heart valves. AB - This report provides retrospective follow-up data on 324 consecutive patients who received a Hancock-I porcine valve in the aortic or the mitral position, or in both positions, between June, 1974, and December, 1976. This analysis included 319 valves (193 mitral, 126 aortic) available for study of the incidence of primary tissue valve failure after 10 to 12.5 years of follow-up. Of the 319 prostheses at risk, 114 instances of primary tissue valve failure occurred. Seventy-three of the failed valves were in the mitral position, and 41 were in the aortic position. The calculated actuarial probability of freedom from primary tissue valve failure was 52 +/- 5% for the mitral and 58 +/- 6% for the aortic prostheses at 12.5 years of follow-up. For patients older than 40 years at the time of operation, the rate of freedom from primary failure was 68 +/- 8% and 55 +/- 6% for aortic and mitral prostheses, respectively, at 12.5 years. Comparison of both actuarial curves disclosed no meaningful difference. However, a tendency toward greater failure rate was observed in the mitral prosthesis group. PMID- 3337580 TI - The relief of pulmonary stenosis by a transatrial versus a transventricular approach to the repair of tetralogy of Fallot. AB - The ratio of peak pressure in the right ventricle to that in the left ventricle (PRV/LV) in the operating room thirty minutes after repair of tetralogy of Fallot by an atrial approach, with or without a concomitant transatrial approach, was 0.58 +/- 0.217. It was 0.52 +/- 0.158 when repair was through a right ventricular approach (p for difference = 0.16). This ratio 18 to 24 hours postoperatively was 0.49 +/- 0.148 and 0.45 +/- 0.121 for the right atrial and right ventricular approaches, respectively. The reduction in PRV/LV between the two observations was -0.09 +/- 0.147 for the right atrial and -0.07 +/- 0.110 for the right ventricular approach (p for difference = 0.4). Therefore, the predictive rules for placing a transannular patch, rules derived from patients in whom the right ventricular approach was used and depending in part on the fall in PRV/LV during the first 24 hours after operation, are also applicable to patients in whom an atrial approach, with or without a transpulmonary approach, is used. PMID- 3337581 TI - Regional changes in myocardial acid production during ischemic arrest: a comparison of sanguineous and asanguineous cardioplegia. AB - Regional differences in myocardial acid production have not been characterized during administration of either asanguineous or sanguineous cardioplegia. To investigate this, miniature glass pH electrodes were placed in the right ventricular (RV) myocardium, the left ventricular subendocardial (LV endo) region, and the subepicardial (LV epi) region in a canine model. Multiple doses of either blood cardioplegia (Group 1; N = 11) or crystalloid cardioplegia (Group 2; N = 11) were administered during 4 hours of aortic cross-clamping. The accumulation of hydrogen ions during the cross-clamp period was greater in Group 2 than Group 1 in the LV endo region (629 +/- 79 nm/L versus 66 +/- 31 nm/L; p less than 0.001), the LV epi region (623 +/- 66 nm/L versus 72 +/- 32 nm/L; p less than 0.001), and the RV myocardium (814 +/- 296 nm/L versus 150 +/- 54 nm/L; p less than 0.05). Within each group, the time course of myocardial pH and the accumulation of hydrogen ions did not differ among the LV endo region, LV epi region, and the RV myocardium (p = not significant). These data indicate that transmural and interventricular differences in myocardial pH and hydrogen ion accumulation are not produced in the vented, arrested canine heart. In addition, when compared with asanguineous cardioplegia, blood cardioplegia globally and transmurally reduces acid accumulation during ischemic arrest. PMID- 3337582 TI - Orthotopic cardiac transplantation for univentricular heart. AB - The technical aspects of orthotopic cardiac transplantation for univentricular heart in a 22-year-old man are discussed. Abnormal pulmonary artery anatomy resulted in right ventricular failure, which was successfully treated. PMID- 3337583 TI - Tuberculous esophagitis with aortic aneurysm fistula. AB - A patient with treated pulmonary tuberculosis and a thoracic aortic aneurysm was seen with a one-month history of dysphagia. Barium swallow revealed a mass in the lower esophagus and extravasation of contrast material into the mediastinum. Endoscopy and biopsy specimens showed acid-fast organisms. The patient was treated with antituberculous drug therapy but bled massively from the gastrointestinal tract and died. Autopsy revealed an aortoesophageal fistula at the level of the thoracic aneurysm. Histopathological study confirmed that this rare tuberculous lesion of the esophagus caused the fistula. PMID- 3337584 TI - Congenital absence of pericardium: an unusual cause of atypical angina. AB - Congenital defects of the pericardium are unusual. Patients may experience exertional chest pain, cardiac arrhythmias, syncope, sudden death, or incarceration of myocardium, or they may be entirely asymptomatic. We describe the case of a symptomatic pericardial herniation diagnosed by echocardiography and confirmed by cineangiography. Successful repair was accomplished using a polytetrafluoroethylene soft-tissue prosthesis. PMID- 3337585 TI - Pericardial hemangiopericytoma as a cause of dysphagia. AB - A 68-year-old woman was seen with recent-onset dysphagia. Investigations suggested a large retrocardiac tumor. At thoracotomy, a highly vascular tumor was found, involving the posterior and left aspect of the pericardium with attachment to the heart. The lesion was partially removed, and histopathological analysis revealed a malignant hemangiopericytoma. To our knowledge, this tumor site and its presentation have not been reported before. PMID- 3337586 TI - Two-cusp plasty for the right ventricular outflow tract in complete repair of tetralogy of Fallot. AB - A procedure termed two-cusp plasty, which prevents pulmonary regurgitation in complete repair of tetralogy of Fallot, is described. PMID- 3337587 TI - Pericardiocentesis under two-dimensional echocardiographic guidance in loculated pericardial effusion. AB - Pericardiocentesis to relieve tamponade from a loculated pericardial effusion in patients following cardiac surgery is greatly aided by two-dimensional echocardiographic imaging guidance. This technique delineates the fluid distribution and the site of adhesions, defines the path for introduction of an aspiration needle, alerts to the possibility of myocardial contact, and helps in positioning the drainage catheter. Two-dimensional echocardiographic imaging can be performed at the patient's bedside, and the images are easy to interpret. This technique simplifies pericardiocentesis and helps to avoid complications. PMID- 3337588 TI - Influenza surveillance in an acute-care hospital. AB - The epidemiology, significance, and clinical consequences of influenza in the hospital setting were studied in a prospective surveillance of adults in an acute care hospital during the 1986-1987 influenza season, specifically searching for cases of nosocomial influenza. A total of 43 cases of influenza A were identified; 17 cases occurred among working hospital employees, 14 cases occurred among patients in the emergency room or clinics, ten were community-acquired cases among hospitalized patients, and two cases were nosocomially acquired. The nosocomial influenza attack rate was 0.3 per 100 hospital admissions. Both cases of nosocomial influenza were associated with secondary pneumonias and prolongation of hospital stay. These cases might have gone unrecognized in the absence of an influenza surveillance program. A potential reservoir of infection was the health care providers caring for the hospitalized patients. Further systematic influenza surveillance is needed to assess the global medical and economic impact of nosocomial influenza on hospitals, rather than simply relying on reports of institutional outbreaks. PMID- 3337589 TI - Premenopausal bone mass is related to physical activity. AB - The relationship between physical activity and bone mass was investigated in 24 healthy, white, premenopausal women (mean age [+/- SE], 39.0 +/- 1.39 years). Physical activity was determined by a sensor that measures movement of the trunk, and bone mineral levels were determined by means of single- and dual-photon absorptiometry and neutron activation analysis. Total physical activity levels were related both to bone mineral density of the spine (r = .41) and to total body calcium levels (r = .51). There was no significant relationship between the bone density of the distal portion of the radius and activity (r = .20). Nonparametric analysis and stepwise multiple regression analysis revealed negative correlations between cigarette smoking and bone density of the spine and radius. These data suggest that the level of physical activity in sedentary white women may be a determinant of peak total skeletal mass and bone density of the spine. PMID- 3337590 TI - Risk of breast cancer in relation to cigarette smoking. AB - To provide additional data on the smoking-breast cancer association, a case control study of 456 cases of breast cancer and 1693 matched controls was conducted among participants in a cancer screening program. The adjusted risk of breast cancer for current smokers was 1.38 (95% confidence interval, 1.01 to 1.90). Analysis of smoking habits restricted to premenopausal women revealed a risk estimate of 2.33 (confidence interval, 1.10 to 4.96) among current smokers and increasing linear trends in risk for number of cigarettes smoked per day and for number of years of smoking. Although smokers had an earlier natural menopause than nonsmokers, there was no evidence of a protective effect of early menopause after adjustment for other factors. These findings suggest that smoking may increase the incidence of breast cancer, especially in premenopausal women. PMID- 3337591 TI - Reversible rostral basilar artery syndrome. AB - We prospectively studied 34 patients with clinical and radiologic evidence of rostral basilar artery syndrome, a vaso-occlusive disorder, who had uniformly excellent short-term functional recovery, in marked contrast to the classic syndrome. All patients displayed important neurobehavioral disturbances, including an acute confusional state, necessitating medical consultation. The composite group had minimal hypertension, significant arrhythmias in the young, and no history of vertebrobasilar insufficiency. Unsuspected cases of idiopathic orthostatic hypotension, as well as cardiac arrhythmias in the elderly, were discovered. A vascular cause was not considered in 79% of those presenting for emergency evaluation and prevented proper acute diagnostic evaluation in 88%. Recognition of this potentially reversible cerebrovascular syndrome may prevent hazardous diagnostic and therapeutic interventions. PMID- 3337592 TI - Autopsy study of the elderly institutionalized patient. Review of 234 autopsies. AB - Autopsies are performed much less frequently in the elderly than in younger patients. Little information exists as to causes of death in the institutionalized elderly. The clinical diagnostic error rate documented by autopsy studies ranges from 6% to 68%. We analyzed the clinical and autopsy records of 234 patients who died during a 14 1/2-year period at our chronic care institution to determine the accuracy of clinical cause of death in addition to the pathologic cause of death. The most common causes of death included bronchopneumonia (33%), congestive heart failure (15%), metastatic carcinoma (14%), pulmonary embolism (8%), myocardial infarction (7%), cerebrovascular accident (6%), unknown cause of death (8%), and a miscellaneous group (9%). The highest diagnostic error rate was in the underdiagnosis of pulmonary embolism (39% antemortem accuracy rate). The most accurately diagnosed condition was cerebrovascular accident (92% antemortem accuracy rate). Pneumonia was correctly diagnosed antemortem in 73% of the patients studied. These data suggest that serious and potentially treatable illnesses are underdiagnosed in the elderly institutionalized patient and that there is valuable information to be learned by performing autopsies in the elderly population. PMID- 3337593 TI - Proteinuria in diabetes. AB - In a population-based study in southern Wisconsin, 1370 diabetic persons diagnosed after 29 years of age were examined using standard protocols to determine the prevalence of proteinuria and associated risk variables. Proteinuria (greater than or equal to 0.30 g/L) was present in 18.0% of persons taking insulin and 12.2% of the persons not taking insulin. Proliferative retinopathy and proteinuria were associated with each other. Proteinuria was also associated with increasing duration of diabetes, high systolic blood pressure, use of digoxin, and being male, but not with a history of cigarette smoking or metabolic control as measured by glycosylated hemoglobin. PMID- 3337594 TI - Computed tomography of the abdomen in the diagnosis of splenic emboli. AB - Abdominal computed tomographic scans were performed in 25 consecutive patients with bacterial endocarditis. Six patients had splenic infarcts, only two of whom had symptoms. Three of the six patients had no evidence of emboli to other organs. In patients with endocarditis who have had clinically apparent emboli or who are, for other reasons, being considered for valvular surgery, a computed tomographic scan of the abdomen may help in decision making. PMID- 3337595 TI - Paroxysmal nocturnal hemoglobinuria associated with the acquired immunodeficiency syndrome. AB - Pancytopenia is a well-recognized manifestation of clinical illness related to human immunodeficiency virus infection. The mechanism of this has been debated, but has been thought to relate either to a nonspecific marrow suppressive effect of opportunistic infections, or to direct involvement of bone marrow hematopoietic precursors as a target of human Immunodeficiency virus. We report the unique temporal association of the acquired immunodeficiency syndrome and paroxysmal nocturnal hemogloblnuria. PMID- 3337596 TI - Boerhaave's syndrome. Computed tomographic findings and diagnostic considerations. AB - Boerhaave's syndrome, or spontaneous rupture of the esophagus, may present with atypical chest pain mimicking an acute thoracic aortic dissection. We describe such a case and discuss the utility of a thoracic computed tomographic scan in arriving at a prompt diagnosis. The importance of early diagnosis is reviewed with particular attention to these roentgenographic findings. PMID- 3337598 TI - Peritoneal sarcoidosis. PMID- 3337597 TI - Pericardial effusion in nephrotic syndrome. PMID- 3337600 TI - Association of primary hyperparathyroidism with myotonic dystrophy in two patients. PMID- 3337599 TI - Nephrotoxicity of common drugs used in clinical practice. PMID- 3337602 TI - Magnesium deficiency in bacteremic patients. PMID- 3337601 TI - Impact of clonidine on alcohol withdrawal states. PMID- 3337603 TI - A year of transition for the Archives. PMID- 3337604 TI - Lowering serum cholesterol. It is time to proceed. PMID- 3337605 TI - The automatic implantable cardioverter-defibrillator. Clinical experience, complications, and follow-up in 25 patients. AB - Twenty-five patients with recurrent ventricular tachyarrhythmias underwent implantation of an automatic implantable cardioverter-defibrillator. The mean length of follow-up was 11.9 +/- 10.8 months. Before the implantation, the patients had survived one or more cardiac arrests (mean, 1.7; range, 1 to 4) and episodes of syncope (mean, 2.2; range, 2 to 3) and had received 6.0 +/- 1.0 antiarrhythmic drug trials. The in-hospital complications included death (two patients), reoperation (one patient), intraoperative myocardial infarction (one patient), sensing-failure (one patient), infection (five patients), and pocket seroma (two patients). The posthospital complications included device failure (four patients), device deactivation (one patient), and inappropriate discharge (two patients). The device discharged appropriately in seven patients due to sustained ventricular tachycardia. During electrophysiologic measurements, the energy requirement for successful cardioversion-defibrillation was related to the type of ventricular arrhythmia induced (monomorphic or pleomorphic ventricular tachycardia or fibrillation). Ventricular tachycardia acceleration occurred in ten patients (40%). No significant changes were found in the size of the electrograms or in the cardioversion threshold during early and late follow-up measurements. Life table analysis showed a 12-month survival rate of 86% and an arrhythmic death survival rate of 100%. We confirm the improved rate of survival in this high-risk group of patients, despite significant complications. PMID- 3337606 TI - Reversible proteinuria in obstructive sleep apnea syndrome. AB - Two patients with severe obstructive sleep apnea syndrome and high-grade proteinuria (greater than 1 g/d [1000 mg/d]) were studied. Three remissions in proteinuria coincided with correction of obstructive sleep apnea syndrome and improvement of blood oxygen levels. These remissions could be dissociated from reductions both in dry body weight and in hematocrit levels. We propose that sleep apnea may cause a functional and reversible type of proteinuria. PMID- 3337608 TI - Psychiatric disability in female carriers of the fragile X chromosome. AB - Fragile X syndrome, an X-linked genetic condition, is an important genetic cause of mental retardation in males. In addition to mental retardation, hemizygous males with fragile X syndrome appear to have a greater likelihood of displaying behaviors classified under the diagnostic category of pervasive developmental disorder than would be expected on the basis of mental retardation alone. Although the majority of female heterozygotes with the fragile X genetic defect are of normal intelligence, our clinical work with this population and a recent case report have suggested that females with fragile X syndrome have an increased rate of schizophrenia spectrum and affective disorders. In this study, the relationship of the fragile X genetic defect to psychopathology in female heterozygotes is investigated by psychiatric evaluation of 35 obligate female carriers of the fragile X chromosome and a comparison group of 24 fragile X negative controls. Female fragile X carriers were found to have a greater frequency of psychopathology associated with schizophrenia spectrum diagnoses, particularly schizotypal features. A weaker association between the fragile X genetic defect and chronic affective disorders was detected. The specificity of the neuropsychiatric phenotype occurring in particular genetic conditions such as the fragile X syndrome adds a potentially valuable tool to the study of psychopathology in the general population. PMID- 3337607 TI - Hyperactive boys almost grown up. II. Status of subjects without a mental disorder. AB - In a previous article we reported the rate of DSM-III diagnoses among 101 male adolescents (aged 16 to 23 years) in whom hyperactivity had been diagnosed between ages 6 and 12 years compared with 100 controls. This report examines the rates of dysfunction among the 52 probands and 80 control adolescents who did not receive a DSM-III diagnosis at follow-up. Contrary to expectations, there were few areas (primarily involving school adjustment) in which the formerly hyperactive children were found to be at a disadvantage and numerous areas (occupational adjustment, temperament, alcohol abuse, antisocial activities, etc) in which the groups were indistinguishable. The results are explained in accordance with a bimodal distribution of dysfunction in hyperactive children grown up. Indirectly, this model supports the construct validity of the DSM-III diagnoses attention deficit disorder with hyperactivity, substance use disorder, and antisocial personality disorder. Post hoc analyses suggest that behavior problems resulting from drug use in early adolescence have graver consequences for previously hyperactive children than normal subjects. PMID- 3337609 TI - Hemodynamic, ventilatory, and biochemical responses of panic patients and normal controls with sodium lactate infusion and spontaneous panic attacks. AB - Hemodynamic, ventilatory, and biochemical variables were measured in ten healthy adults and ten panic patients during infusion of 0.5 mol/L of sodium lactate. Physical activity, fitness level, and ambulatory electrocardiograms were also recorded. Lactate infusion doubled cardiac output, increased blood lactate levels by sixfold, and produced hypernatremia, hypocalcemia, and decreased serum bicarbonate levels in both groups but raised arterial pressure only in the patients. The patients hyperventilated before and during the infusion. Physiological responses and somatic complaints with the infusion differed little between the groups, but emotional complaints were six times more frequent among the panic patients. Eight patients but no control subjects interpreted their symptoms as a panic attack. Heart rate increased with only 14 of 31 recorded spontaneous outpatient panic attacks. Sodium lactate infusions appear to produce panic by mimicking the physiology of spontaneous panic. Treatment with cardioactive agents is not indicated in the absence of cardiopulmonary or autonomic nervous system abnormalities. PMID- 3337611 TI - Lithium augmentation of antidepressant treatment: partially due to an effect on a cholinergic mechanism? PMID- 3337610 TI - Reliability of the telephone interview in diagnosing anxiety disorders. AB - The reliability of psychiatric diagnosis using the Schedule of Affective Disorders and Schizophrenia-Lifetime Version in personal and telephone interviews with 39 subjects was assessed using a 12- to 19-month test-retest design. Interrater reliability was high (kappa, .69 to .84) for the diagnosis of panic disorder, agoraphobia with panic attacks, probable panic disorder, major depression, and alcohol abuse. We conclude that it is possible to reliably make these lifetime diagnoses in a family study using the telephone interview. PMID- 3337612 TI - Morbid risk in first-degree relatives of persons with Alzheimer's disease. PMID- 3337613 TI - High intercorrelations among urinary outputs of norepinephrine and its major metabolites. A replication in depressed patients and controls. AB - We examined the intercorrelations among urinary outputs of norepinephrine (NE) and its three major metabolites in unipolar depressed patients (n = 28) and normal controls (n = 24). Among the depressed patients, levels of NE correlated with normetanephrine (NM), 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid (VMA), and VMA correlated with NM and MHPG. In the total group of depressed and control subjects (n = 52), the sum of NE and its major metabolites correlated with urinary outputs of NE, NM, MHPG, and VMA. These highly significant correlations among urinary outputs of NE and its major metabolites replicate a previous report of strong correlations among these same four urinary substances in a smaller group of depressed patients. PMID- 3337614 TI - The diurnal variation in plasma homovanillic acid level persists but the variation in 3-methoxy-4-hydroxyphenylglycol level is abolished under constant conditions. AB - Plasma concentrations of homovanillic acid (HVA) and 3-methoxy-4 hydroxyphenylglycol (MHPG) were determined every two hours for two consecutive days in seven depressed patients and seven matched normal controls. On the first day subjects followed their regular ward routine. On the second day they were placed on a regimen in which activity, posture, diet, and wakefulness were held constant. There were significant diurnal variations in both MHPG and HVA concentrations on the baseline day, whereas on the constant routine, a diurnal variation was present only in HVA. We conclude that diurnal variations in plasma MHPG are evoked by changes in physical activity, posture, or other factors controlled on the constant routine, and that a major component of the diurnal variation in plasma HVA concentrations is regulated by a circadian oscillator that is independent of sleep or activity. PMID- 3337615 TI - Serotonin function in obsessive-compulsive disorder. A comparison of the effects of tryptophan and m-chlorophenylpiperazine in patients and healthy subjects. AB - To evaluate the role of serotonin (5-HT) function in obsessive-compulsive disorder (OCD), behavioral and biochemical responses to the 5-HT receptor agonist m-chlorophenylpiperazine (MCPP) and the 5-HT precursor tryptophan were examined in healthy subjects and patients with OCD. Baseline prolactin levels and the prolactin rise following MCPP were significantly reduced in female patients compared with female healthy subjects. In contrast, the increase in prolactin level following tryptophan administration was not significantly different between male or female patients with OCD and the respective sex-matched healthy subjects. The prolactin responses to MCPP and tryptophan were both significantly higher in female patients and healthy subjects than in their male counterparts. The cortisol and growth hormone responses to MCPP and tryptophan were similar in the patients and healthy subjects and were not related to gender. The behavioral responses to MCPP or tryptophan were not consistently different between patients and healthy subjects, and neither MCPP nor tryptophan had effects on obsessive or compulsive symptoms. These results lend only partial support to the hypothesis that 5-HT dysfunction may be linked to the pathophysiology of OCD and point to the need for the evaluation of other neurotransmitter systems in future investigations of OCD. PMID- 3337616 TI - Adult schizophrenia following prenatal exposure to an influenza epidemic. AB - In the context of a Finnish birth cohort, we tested the hypothesis that viral infection during the latter two thirds of fetal development would increase the risk of adult schizophrenic outcome. Psychiatric hospital diagnoses were recorded for all individuals in greater Helsinki who were fetuses during the 1957 type A2 influenza epidemic. Those exposed to the viral epidemic during their second trimester of fetal development were at elevated risk of being admitted to a psychiatric hospital with a diagnosis of schizophrenia. This was true for both males and females and independently in several psychiatric hospitals. The second trimester effect was seen in the elevated proportion of schizophrenics among those admitted to a psychiatric hospital and also in higher rates of schizophrenia per 1000 live births in the city of Helsinki. The study has several limitations: (1) We have no direct evidence that the subjects actually suffered a viral infection. (2) The psychiatric data were obtained only for subjects up to the age of 26 years, 56 days. (3) The findings are based on hospital diagnoses. (4) The determination of stage of gestation at time of exposure to the epidemic is based on date of birth. The viral infection might have occurred outside the official epidemic window; the infant may have had a preterm or postterm delivery. These sources of error, however, should not serve to enhance the findings. The observed viral effect is interpreted as being one of many potential perturbations of gestation. We suggest that it is less the type than the timing of the disturbance during fetal neural development that is critical in determining risk for schizophrenia. PMID- 3337617 TI - Mesenteric venous thrombosis due to antithrombin III deficiency. AB - A 19-year-old woman developed gradually worsening abdominal pain, signs of peritonitis, and hematemesis. Laparotomy revealed peritonitis due to segmental small-bowel infarction, and the underlying pathologic condition was mesenteric vein thrombosis. A primary thrombotic disorder was suggested and antithrombin III deficiency was found. Before anticoagulant therapy could be initiated, she developed hemorrhagic cerebral infarction and died. Her history included three episodes of deep vein thrombosis while taking oral contraceptives. Her father died of spontaneous mesenteric and portal vein thrombosis at age 29 years. This report underlines the importance of careful interpretation of the vascular pathology in cases of intestinal ischemia. PMID- 3337618 TI - Immunocytochemistry of the thyroid in surgical and cytologic specimens. AB - The value of immunocytochemistry in thyroid disease was evaluated in histologic and cytologic material derived from papillary carcinoma (25 cases), follicular carcinoma (nine cases), follicular adenoma (nine cases), Hurthle cell tumor (three cases), medullary carcinoma (two cases), nodular goiter (nine cases), and Hashimoto's thyroiditis (two cases). Thyroglobulin was positive in the follicular cells and/or colloid of all lesions (except medullary carcinoma) and two papillary carcinomas. Vimentin was positive in papillary carcinoma (17 of 25), follicular carcinoma (four of nine), follicular adenoma (four of nine), and nodular goiter (two of nine). Vimentin positivity, which was restricted to follicular cells, was strongest in those cells undergoing oncocytic transformation. Three markers of glandular/acinar secretory differentiation (lactoferrin, lactalbumin, and secretory component) were uniformly negative even in well differentiated follicular structures. In medullary carcinoma, both calcitonin and carcinoembryonic antigen were strongly positive in the parafollicular cells. The antibody panel can definitely identify histogenesis from the thyroid but is of little value in tumor classification. In histologic and cytologic preparations, vimentin positivity does not exclude thyroid follicular cell origin. The method can be successfully applied to richly cellular needle aspirates. This is best achieved with assisted needle aspirations when cellularity is ascertained by on-site microscopic examination of multiple passes. PMID- 3337619 TI - Pleural amyloidosis. AB - Pleural amyloidosis has been reported rarely, and the diagnosis of this disease by Cope needle biopsy has, to our knowledge, been reported only once previously. We report two patients in whom the diagnosis of pleural amyloidosis was made by biopsy specimens obtained in the examination of large, unilateral pleural effusions. In one patient, the diagnosis was made by Cope needle biopsy. The clinical and diagnostic significance of these cases are discussed. PMID- 3337620 TI - Skeletal myxoid chondrosarcoma with microtubular aggregates within rough endoplasmic reticulum. AB - A skeletal myxoid chondrosarcoma of the femur was examined by light and electron microscopy. Light microscopic features were characteristic for myxoid chondrosarcoma or "chordoid sarcoma." Electron microscopy disclosed crystalline arrays of microtubules within dilated rough endoplasmic reticulum, a feature previously described in extraskeletal myxoid chondrosarcomas. Tumors with the histologic characteristics of extraskeletal myxoid chondrosarcoma ("chordoid sarcoma") occurring in bone have been rarely reported. We describe herein such a tumor and document the existence of distinct microtubules within the endoplasmic reticulum. PMID- 3337621 TI - Metaplastic breast carcinoma with epithelial phenotype of pseudosarcomatous components. AB - A case of metaplastic breast carcinoma was subjected to an immunohistochemical study to characterize its apparent fibrosarcomatous and chondrosarcomatous elements. Polyclonal and monoclonal antibodies against epithelial cell components such as keratin proteins, epithelial membrane antigen, membrane and cytoplasmic antigens of human mammary carcinoma cells, and carcinoembryonic antigen were used, as well as antibodies against the mesenchymal antigens, desmin, and vimentin. The cells with a mesenchymal appearance had an epithelial derivation, as shown by the presence of epithelial cell markers and absence of mesenchymal cell markers. PMID- 3337622 TI - Late recurrence (33 years) of a gastric epithelioid stromal tumor (leiomyoblastoma) with low malignant potential. AB - A recurrence of a gastric epithelioid stromal tumor (leiomyoblastoma) 33 years after incomplete resection and radiation therapy is reported. The original tumor involved the posterior gastric wall and presented with intraperitoneal hemorrhage. A tumor recurrence was found attached to the stomach with invasion through the wall of the splenic flexure of the colon. The histologic features of the tumor had not significantly altered, except for a slight increase in mitotic rate. Neither the original tumor nor the recurrence exhibited smooth-muscle differentiation on ultrastructural or immunohistochemical examination, suggesting an origin from an undifferentiated or primitive mesenchymal cell. The term leiomyoblastoma, although established in the literature, should be reserved for epithelioid tumors in which myoid differentiation can be established. The long interval to recurrence supports the suggestion that all of these tumors have at least a low-grade malignant potential. PMID- 3337623 TI - Primary myxoid chondrosarcoma of the thyroid gland. AB - We describe a case of primary myxoid chondrosarcoma of the thyroid gland that occurred in a 68-year-old man. To our knowledge, this is the first case of such a tumor reported in the english literature under this name. PMID- 3337624 TI - Lateral cervical cyst containing gastric epithelium. AB - A lateral cervical cyst, presumably of branchial origin, was found to contain gastric epithelium. This is an extremely rare condition and, to our knowledge, represents the first such report in a branchial cyst. The literature is reviewed and speculations are made with respect to the embryologic and clinical implications of this anomaly. PMID- 3337625 TI - Papillae formation in parathyroid adenoma. A source of possible diagnostic error. AB - Parathyroid adenomas, the most common cause of hyperparathyroidism, display diverse histologic patterns. The majority of adenomas form solid masses or show nodular, trabecular, and acinar patterns. In a four-year review of data on 103 surgically resected parathyroid adenomas, we encountered only a single case that showed papillae formation. We report this case to illustrate occurrence of this unusual histologic pattern that might create a diagnostic problem. PMID- 3337626 TI - Pathology of the heart in acquired immunodeficiency syndrome (AIDS) PMID- 3337627 TI - Squamous cell carcinoma of the ovary. PMID- 3337628 TI - Pseudomonas cepacia-associated pneumonia in cystic fibrosis. Relation of clinical features to histopathologic patterns of pneumonia. AB - We studied lungs at autopsy from 40 patients with cystic fibrosis (CF) to determine the structural and clinicopathologic features of pneumonia associated with Pseudomonas cepacia respiratory tract colonization. Three clinical groups were identified: group A included 11 patients exhibiting a fulminant course following P cepacia colonization; group B included 20 patients who declined slowly following colonization; and group C included nine patients without P cepacia colonization. Acute pneumonia occurred in all groups but was most extensive and necrotizing in group A. Chronic lobular pneumonia involved all groups equally, whereas interstitial pneumonia predominated in group B. Diffuse alveolar damage occurred infrequently in all groups. Combinations of structural patterns were frequently seen. We conclude that, although there is great overlap in the structural appearance of pneumonia among patients with CF with different bacterial colonization histories, the evidence suggests that P cepacia is a cause of necrotizing pneumonia in some patients. Factors that predispose to this fulminant lung infection are poorly understood. PMID- 3337629 TI - Varicella-zoster virus leukoencephalitis and cerebral vasculopathy. AB - Two patients with varicella-zoster virus leukoencephalitis and acquired immunodeficiency syndrome are described. Neither patient had cutaneous or disseminated varicella-zoster virus infection within the last six months of life. Demyelinated lesions resembling those of progressive multifocal leukoencephalopathy were seen in their brains at autopsy. Numerous cells with Cowdry type A intranuclear inclusions surrounded the lesions; these cells stained positively for varicella-zoster virus with immunohistochemistry and contained herpesvirus nucleocapsids by electron microscopy. Leptomeningeal vessels accompanying the lesions displayed a zoster-induced vasculopathy in one of the two patients. Vascular and parenchymal central nervous system infections with varicella-zoster virus are rare in the absence of cutaneous lesions, and to our knowledge, the presence of both in one patient has not yet been described. PMID- 3337630 TI - The causes of morbidity and mortality among infants born at term. AB - Previous studies have reported on the pathologic spectrum of perinatal mortality; however, in our opinion, the problems pertaining to the term newborn have not been emphasized sufficiently. We reviewed the autopsies of all term infants up to 2 months of age in a ten-year period (July 1975 to July 1985). These 342 patients comprised 20% of all pediatric autopsies. The patients were grouped according to cause of death in the following categories: congenital anomalies (59%); infection (10%); perinatal injury, including meconium aspiration (9%); maternal-placental problems (11%); and miscellaneous (5%). In 4% of the cases, mainly stillbirths, the cause of death was unclear. Of the congenital anomalies, the cardiovascular system was most affected (57%). Hyaline membrane disease and intraventricular hemorrhage, usually frequent in series involving many preterm patients, were seldom seen. This study emphasizes the different pathologic spectrum of mortality between premature and term newborns. PMID- 3337632 TI - Ependymoma of the mediastinum. AB - A case of primary ependymoma of the mediastinum is reported. The tumor was adherent to the lung and metastasized to adjacent mediastinal lymph nodes. An autopsy showed no evidence of tumor in the central nervous system. The diagnosis of ependymoma was confirmed by the immunohistochemical positivity for glialfibrillary acidic protein. To the best of our knowledge, this is the first reported example of an ependymoma in this location. PMID- 3337631 TI - Mesodiverticular band and sudden death in children. A report of two cases. AB - Meckel's diverticulum is occasionally associated with a fibrous band, which connects the tip of the diverticulum to the mesentery. Beneath this mesodiverticular band, herniated loops of small bowel can incarcerate and infarct. The high mortality rate and the suddenness of death associated with this internal hernia make it important to the forensic pathologist. PMID- 3337634 TI - The citizen physiatrist. PMID- 3337633 TI - Cytoplasmic granular change of Sertoli cells in two cases of Sertoli-cell-only syndrome. AB - The testicular biopsy specimens of two cases of Sertoli-cell-only syndrome are described, in which some of the Sertoli cells are filled with coarse cytoplasmic eosinophilic granules. Histochemical stains suggest that the granules contain glycocompounds and phospholipids. On electron microscopy, the granules prove to be densely populated secondary lysosomes, containing membrane fragments, phospholipid-like materials, and other amorphous masses of various densities. Whether the excessive secondary lysosomes arise as a result of some metabolic block in the Sertoli cells, or merely represent autophagy in response to the absence of germ cells, cannot be determined. A search of the literature indicates that this is the first instance, to our knowledge, in which such changes are reported in Sertoli-cell-only syndrome. PMID- 3337635 TI - Magnetic resonance imaging and degree of disability in multiple sclerosis. AB - Sixteen patients with multiple sclerosis were evaluated by magnetic resonance imaging (MRI) to determine if number of brain lesions correlated with the amount of functional disability, as described by the Incapacity Status Scale contained in the Minimal Record of Disability. Although no correlation existed, the statistical analysis did indicate a trend toward correlation, which warrants a study with a larger number of subjects. PMID- 3337636 TI - Muscle strengthening through high-resistance weight training in patients with neuromuscular disorders. AB - The effects of weight training on muscle performance were quantified by measuring (1) maximum force (muscle strength), (2) force-time integral--area under force time plot during 60 seconds of sustained maximum force (work done), and (3) fatigue index--percentage reduction in maximum force. Subjects included 16 patients with gradually progressive neuromuscular disorders. The muscle strength of these patients ranged from 2% to 75% normal before the program. For patients with markedly to moderately weak muscles, maximum force increased by 80% +/- 48%, force-time integral increased by 132% +/- 93%, and mean fatigue index was significantly reduced from 53% +/- 18% to 34% +/- 7.7% during the study period. Severely weak muscles (less than 10% normal strength) generally did not improve. High-resistance weight training can significantly increase muscle performance of patients with neuromuscular disease if disease progression is slow and initial muscle strength is greater than 15% normal. PMID- 3337637 TI - Biofeedback conditioning for fecal incontinence. AB - Twenty-one subjects suffering daily from fecal incontinence were treated with biofeedback training as a rehabilitative trial. Fifteen of these patients had incontinence following surgical interventions; the other six had senile incontinence. A device was employed to record the pressure existing at the level of the anal canal and to stimulate the rectal ampulla to control the performance of the external anal sphincter and the sensibility of the rectum. Of the 31 treated patients, eighteen (86%) presented good results with satisfactory recovery of anal incontinence, and three subjects (14%) showed unsatisfactory results (more than one episode of incontinence monthly). Although both groups of patients showed improvement in external anal sphincter contraction, the sensibility of the rectum to endoluminal distention improved more in good responders. The employment of biofeedback training to obtain improvement of the threshold of rectal sensibility (minimal volume of endoluminal distention to produce the sensation of imminent defecation and external anal sphincter contraction) has proved useful in the rehabilitation of incontinent patients. PMID- 3337638 TI - Neurologic complications of thyrotoxicosis: case report. AB - Weakness accompanying hyperthyroidism may be due to a variety of causes. A case is presented of a patient who, during management of thyrotoxicosis, became quadriparetic due to a unique combination of axonal neuropathy, myopathy, and pyramidal tract dysfunction. Electrodiagnostic, muscle biopsy, and nerve biopsy results are presented. PMID- 3337639 TI - Bilateral obturator nerve injuries during urologic surgery. AB - Obturator nerve injury can result from prolonged acute hip flexion. Bilateral obturator nerve compromise developed in a patient as a result of prolonged urologic surgery. The clinical and electromyographic findings were consistent with this diagnosis. The nerve injury was believed to result from stretching at the bony obturator foramen. Management included a trial of steroids, gait training, and instruction on avoiding acute hp flexion. The clinical and EMG abnormalities disappeared. Awareness of this occurrence and an understanding of the anatomy may avoid confusion with other conditions and permit accurate diagnosis. PMID- 3337640 TI - Calf enlargement associated with neurologic disease: two uncommon cases. AB - Muscle enlargement and hypertrophy are rare findings in neurogenic lesions. The two in combination have been reported in cases of peripheral nerve lesions, polyneuropathy, and poliomyelitis. True and pseudo muscle hypertrophy are the two possible etiologies, whereas infiltration, stretch, or exercise of the muscle are the causative factors. We report two cases of unilateral calf enlargement, one occurring after surgery for S1 radiculopathy with associated cramping, and the other after poliomyelitis. PMID- 3337641 TI - Magnetic resonance imaging for vertebral-basilar system infarction. AB - The rehabilitative course for patients who have suffered vertebral-basilar vascular lesions is often interrupted by intermittent episodes of increasing dizziness, nausea, vomiting, and ataxia. Since CT studies of the brain do not always visualize these lesions reliably, the rehabilitation specialist has been without a diagnostic tool to distinguish between progressive and stable vertebral basilar system infarctions. Magnetic resonance imaging (MRI) offers a safe, noninvasive, sensitive means of monitoring vascular lesions in the posterior fossa. The purpose of this study was to use MRI to evaluate patients with suspected vertebral-basilar vascular lesions. In three patients studied, MRI was superior to CT scan. Advantages of MRI included lack of artifact due to bone scattering from ionizing radiation, ability to image directly in the sagittal plane, visualization and localization of pathologically smaller lesions, and potential for performing serial studies without exposing patients to large doses of radiation. In each case, MRI data yielded valuable adjunctive information that aided further rehabilitation evaluation and management. We conclude that MRI may be a useful diagnostic and prognostic tool in evaluating and managing rehabilitation patients with vascular lesions involving the vertebral-basilar system. PMID- 3337642 TI - Patient motion detecting method. AB - In order to find an effective method for monitoring restless, agitated, and confused patients, we used an infrared sensing device placed above the patient's bed. This device was more useful than the previously available pressure transducer, which is placed beneath the patient's mattress. The infrared sensing device was more accurate, less cumbersome, generally easier to operate, and less likely to be tampered with than the pressure transducer. PMID- 3337644 TI - Triceps spasticity. PMID- 3337643 TI - Physiatric practice characteristics: report of a membership survey. AB - In 1986 the Board of Governors of the American Academy of Physical Medicine and Rehabilitation commissioned a survey of the Academy's membership to determine the practice patterns of physiatrists. Responses were received from 1,115 members (75%). Approximately 65% of respondents are under 43 years old; 64% are graduates of American medical schools. Fifty-six percent practice in communities with populations of 500,000 or more persons; only 9% practice in communities of less than 50,000 people. Nearly 53% practice in a single setting and the average work week is 50.6 hours, with most of those hours spent in some aspect of patient care. The most frequent diagnosis in all practice settings is pain syndrome; consultation is the primary activity. Survey results show that physiatry is still primarily a hospital-based specialty, although significant time is spent in office-based settings. Data gleaned from this first attempt at an extensive analysis of physiatric practice characteristics will be utilized in planning how to meet future needs of the specialty, its practitioners and their patients. PMID- 3337645 TI - SNAP recording technique. PMID- 3337646 TI - Teaching PM&R in Israel. PMID- 3337647 TI - Modification of the end-to-end stapled anastomosis utilizing intersecting staple lines. AB - There have been many technical advances involving intestinal stapling instruments. We have modified the method of the end-to-end anastomosis (EEA) stapling instrument. This requires the use of an intersecting staple line in a manner not previously described, to our knowledge. We report our technique that has been successful in the ten patients in whom it has been used; there have been no complications. PMID- 3337649 TI - Treatment of rectal carcinoma. PMID- 3337648 TI - Pleurectomy through the triangle of auscultation for treatment of recurrent pneumothorax in younger patients. Evaluation of 60 consecutive cases. AB - Sixty patients, aged 14 to 35 years, with recurrent pneumothorax were treated with pleurectomy through the triangle of auscultation, with no chest wall muscle transection. The advantages of this approach over a full thoracotomy are that with no muscle transection, a shorter postoperative recovery is expected and, subsequently, early return to normal activity is achieved. The scar may also be more cosmetically acceptable. There was no postoperative mortality, and only one patient required reoperation because of bleeding. The technique is simple, and exposure is adequate. If necessary, this limited thoracotomy can be converted to a full thoracotomy with no difficulty. PMID- 3337650 TI - Reducing wound infections: gown and drape barriers. PMID- 3337651 TI - 'Noninvasive' treatment of esophagogastric anastomotic leakage. PMID- 3337652 TI - The prevention of pulmonary complications after upper abdominal surgery in patients with noncompromised pulmonary status. AB - Controversy exists regarding the routine use of breathing exercises in the prevention of pulmonary complications after upper abdominal surgery. We prospectively randomized 153 patients who had noncompromised pulmonary status; the control group (84 patients) engaged in no breathing exercises, and the respiratory therapy group (69 patients) engaged in preoperative and postoperative breathing exercises supervised by the physical therapist. Postoperative pulmonary complications were classified using criteria derived from chest roentgenograms, arterial blood gas samples, and temperature registration. The incidences of postoperative complications in the treatment group and in the control groups were 19% and 60%, respectively. In the present study, preoperative lung function tests had no additional or predictive value. We advise preoperative and postoperative breathing exercises as a prophylactic treatment in all patients scheduled for upper abdominal surgery. PMID- 3337653 TI - Alpha-adrenergic blocker for posthernioplasty urinary retention. Prevention and treatment. AB - In a prospective, randomized study, 102 patients over the age of 60 years underwent inguinal hernioplasty. We compared a group of 58 patients who received phenoxybenzamine hydrochloride with a control group of 44 patients. The phenolsulfonphthalein test was performed in all patients. Twenty-six (25.5%) of the 102 patients developed acute urinary retention after the hernioplasty; all of them were in the control group. All of these 26 patients had pathological phenolsulfonphthalein test. In 21 of these 26 patients, urinary retention disappeared within 48 hours following phenoxybenzamine administration. PMID- 3337654 TI - The role of fine-needle aspiration in the management of solid breast masses. AB - Fine-needle aspiration cytology is a safe, inexpensive, rapid method of establishing the diagnosis of breast cancer in patients with solid, palpable masses. The pathologist must be conservative in his interpretation of malignancy so that positive study results occur only in patients with cancer. We compared the cytologic diagnosis of 140 breast masses with the histologic diagnosis. Seventy of 98 breast cancers were diagnosed by this technique. Because 28 cancers could not be diagnosed with certainty, open biopsy should be performed on all breast masses with nonmalignant cytologic findings. PMID- 3337655 TI - Intestinal obstruction in patients with ovarian cancer. Variables associated with surgical complications and survival. AB - Intestinal obstruction is frequently encountered in patients with ovarian cancer. Surgical correction of intestinal obstruction may allow the prolonged survival of some patients. We identified prognostic factors associated with operative complications and postoperative survival. Multiple preoperative, intraoperative, and postoperative variables were considered. In addition, a previously published prognostic index was evaluated. Statistical assessment developed a model that demonstrated that the clinical assessment of tumor status, the serum albumin level, and the nutrition score were variables significantly associated with postoperative survival. The amount of residual ovarian cancer at the completion of bowel obstruction surgery was also significantly associated with postoperative survival. This information may aid in the preoperative selection of patients who might benefit from surgical correction of intestinal obstruction. PMID- 3337657 TI - Pain insensitivity in schizophrenic patients. A surgical dilemma. AB - Some schizophrenic patients have decreased pain perception while others have decreased pain expression. These factors frequently lead to difficulties in the diagnosis of acute intra-abdominal surgical emergencies. Increasingly large numbers of schizophrenic patients are being cared for in the community. It is therefore imperative that surgeons be acutely aware of the diagnostic dilemmas presented by this group of patients so that misdiagnosis is avoided and appropriate surgical therapy is instituted in a timely manner. PMID- 3337656 TI - Correlation of presence of granulomas with clinical and immunologic variables in Crohn's disease. AB - Approximately 50% of patients with Crohn's disease have epithelioid granulomas present in the diseased intestine. Some studies have associated the presence of granulomas with a good prognosis. In this prospective study, 44 patients with Crohn's disease requiring surgery were followed up for five years. Twenty-two patients (50%) had granulomas. Patients with granulomas were younger and had a shorter duration of disease. They also had more extensive disease and a greater degree of peripheral lymphopenia. Follow-up showed a trend toward greater recurrence rate in the patients with granulomas. It seems that patients with aggressive and extensive Crohn's disease are not protected from the development of symptomatic early recurrence by the presence of epithelioid granulomas. PMID- 3337658 TI - Results of a mass screening program for colorectal cancer. AB - Following a series of educational newscasts about colorectal cancer that were aired on a local television news program, stool guaiac slide kits were distributed on request to 72,000 persons in Memphis. One or more slides were positive In 1310 (6%) of the 23,000 kits returned. Of the 1310 individuals with positive cultures, 597 (45%) saw a physician for further evaluation. Sixty-five of these persons received inadequate evaluations. Of the 532 individuals (90%) who received adequate evaluations, 154 (26%) had no evidence of pathology that would account for occult blood. Of the remaining 443 persons, 26 were found to have colorectal cancer, and 20 of these 26 persons were found to have surgically amenable lesions (Dukes' stages A through B2). In addition, 67 potentially precancerous polyps were found. Mass screening for colorectal cancer using guaiac slide tests, coupled with patient compliance for a screening protocol and adequate follow-up evaluation, has the potential to identify and treat early colorectal cancer. PMID- 3337659 TI - Delayed muscular rigidity and respiratory depression following fentanyl anesthesia. AB - A delayed effect of fentanyl used for anesthesia may be respiratory distress several hours after surgery. The findings are muscular rigidity, fall in chest wall compliance, hypoventilation, respiratory acidosis, and hypotension. In the past, to our knowledge, this complication was exclusively reported in patients undergoing cardiac surgery, when large fentanyl dosages are employed. This article describes three general surgical patients in whom respiratory distress developed three to five hours following colon surgery when a moderate dose of fentanyl citrate, 55 to 75 micrograms/kg, was used. Initially, all patients had a normal recovery from anesthesia. Later, respiratory distress was successfully treated with a fentanyl antagonist and ventilatory assistance. This delayed toxic phenomenon is thought to be due to the reentry of fentanyl into plasma from deposits in adipose tissue, muscle, and the gastrointestinal tract, leading to a secondary rise in the plasma concentration. It is more likely to be encountered when hypothermia, rewarming, and acidosis are present in the postoperative period. This life-threatening complication is treacherous, since it may occur when the patient has been transferred to the surgical ward and is less closely monitored. PMID- 3337660 TI - Pseudohyperparathyroidism secondary to gigantic mammary hypertrophy. AB - Pseudohyperparathyroidism encompasses both ectopic hyperparathyroidism and the more commonly encountered nonparathyroid humoral hypercalcemia of malignancy- metastatic breast cancer being the classic example. Benign breast disease is a rare cause of hypercalcemia. We recently managed a patient with gigantic mammary hypertrophy that occurred during pregnancy who concomitantly manifested marked nonparathyroid hypercalcemia. This report strongly suggests that a casual relationship exists between benign breast disease and hypercalcemia. PMID- 3337661 TI - Fragmentation of biliary tract stones by lithotripsy using local anesthesia. AB - Extracorporeal shock wave lithotripsy has become an important mode of therapy for renal lithiasis in patients who cannot withstand surgery. Recently, this method has been successful in fragmenting biliary stones in selected healthy patients. We report the successful fragmentation of biliary stones after the administration of local anesthesia in two patients who were poor surgical risks. PMID- 3337662 TI - Villous adenoma of the common bile duct. AB - A patient with villous adenoma of the common bile duct presented with obstructive jaundice, weight loss, and icterus. Results of preoperative evaluation suggested cancer of the pancreas or common bile duct. Despite normal findings of intraoperative needle biopsies, a duodenopancreatectomy was performed. Three years after operation the patient is without significant problems. We present the surgical challenge of treating this unique entity. PMID- 3337663 TI - Cerebral mucormycosis in two cases of acquired immunodeficiency syndrome. AB - We describe two patients with isolated cerebral mucormycosis and acquired immunodeficiency syndrome (AIDS). Their clinical course was rapid and fatal; early diagnosis and treatment with amphotericin B did not prevent a fatal outcome in both cases. Isolated cerebral mucormycosis has not (to our knowledge) been reported previously in patients with AIDS. Mucormycosis should be included in the differential diagnosis of central nervous system infections in intravenous drug abusers with AIDS. A brain biopsy is needed for the diagnosis of mucormycosis. PMID- 3337664 TI - Striatal syndrome following hyponatremia and its rapid correction. A manifestation of extrapontine myelinolysis confirmed by magnetic resonance imaging. AB - Several pathologic reports have indicated the occurrence of extrapontine sites of myelinosis associated with electrolyte disturbance and its rapid correction. Clinical evidence of the presence of such lesions, however, have rarely been described. We report a case of a 50-year-old man who following rapid correction of electrolyte imbalance developed a profound striatal syndrome. The clinical manifestations, the course of his illness as well as response to therapy, confirmation of lesion sites by magnetic resonance imaging (MRI), and abnormalities on visually evoked potentials are described in detail. PMID- 3337665 TI - Cardiovascular autonomic dysfunction in Guillain-Barre syndrome. Therapeutic implications of Swan-Ganz monitoring. AB - Guillain-Barre syndrome (GBS) is an acute inflammatory polyneuropathy that may lead to quadriparesis, ventilatory failure, and autonomic dysfunction. While significant mortality due to ventilatory failure has been associated with this syndrome, this complication can now be readily managed. However, an estimated mortality of 5% to 20% remains attributable to medical complications (pulmonary embolus, sepsis) and to acute cardiovascular collapse due to autonomic failure. In this report, detailed sequential changes in hemodynamic parameters, as measured by Swan-Ganz catheter, associated with severe autonomic cardiovascular instability in a patient with GBS are described. Knowledge of changes in these hemodynamic parameters led to optimal therapy. Long-term Swan-Ganz monitoring in an intensive care setting may dramatically benefit the critically ill patient with GBS and cardiovascular autonomic dysfunction, and may help to eliminate the residual morbidity and mortality associated with this disease. PMID- 3337666 TI - Modification of Parkinson's disease by long-term levodopa treatment. PMID- 3337667 TI - Timing of levodopa in parkinsonism. PMID- 3337668 TI - Reaction time and catecholamine in Parkinson's disease. PMID- 3337669 TI - Shunting during carotid endarterectomy. PMID- 3337670 TI - Talking to comatose patients. AB - Physicians may not talk to comatose patients for several reasons. Comatose patients do not seem to hear or respond. Speaking may not affect their clinical outcome; time spent with them takes time away from other, more "viable" patients. Comatose patients may, however, hear; many have normal brain-stem auditory evoked responses and normal physiologic responses to auditory stimuli. Not talking to comatose patients may promote the notion that they are dead or nearly dead; not talking may become a self-fulfilling prophecy, influencing physicians to inappropriately withhold or withdraw therapy. Because comatose patients are especially vulnerable, and because some comatose patients may recover, physicians should consider talking to these patients. Our analysis suggests that families, medical students, and house staff would benefit from the humane example modeled by those clinicians who care for and talk to all patients. PMID- 3337672 TI - Reliability of the Washington University Clinical Dementia Rating. AB - There is a growing need for methods for measuring and staging the natural history of dementia of the Alzheimer type. One instrument, designed with that purpose in mind, is the Washington University Clinical Dementia Rating. We tested its reliability using multiple clinicians in a videotape-design study, and it proved reliable under these study conditions. PMID- 3337671 TI - Clinical determination of mental competence. A theory and a retrospective study. AB - In an attempt to establish a method for determination of mental competence, a two part investigation was undertaken. First, a model for mental competence was devised that would be applicable across a broad range of neurologic disorders; this model was based on a patient's ability to make complex decisions. Second, a retrospective analysis of competence in 92 inpatients on a neurobehavioral service was carried out. The model was a useful way to view competence, at least in this population. Competence could be classified as operational, limited to a single cognitive domain, or as general, cutting across all domains in a way for which no compensation could be devised. The results suggest that a model of competence based on analysis of individual cognitive operations will provide a sound clinical approach to a common problem that is presently not well characterized. PMID- 3337673 TI - Focal and/or lateralized polymorphic delta activity. Association with either 'normal' or 'nonfocal' computed tomographic scans. AB - Focal continuous polymorphic delta activity (PDA) is classically taught to be associated with destructive lesions of cerebral white matter. One hundred patients with focal or lateralized continuous PDA recorded by an electroencephalogram who also had computed tomographic (CT) scans of the head performed at approximately the same time were studied. Thirty-three percent had normal or "nonfocal" abnormalities on their CT scans. Most of these had a history of either seizures (51%) or transient cerebral ischemia/stroke (27%); however, a wide variety of causes were possible. This high percentage of patients with focal continuous PDA without corresponding CT scan lesions supports the concept that the electroencephalogram is a physiologic study that is complementary to anatomic imaging techniques. PMID- 3337674 TI - Central nervous system magnetic resonance imaging findings in myotonic dystrophy. AB - We evaluated findings in 14 patients with myotonic dystrophy (MD) using magnetic resonance imaging of the brain and compared them with those in age-matched controls with headache. There was an increased incidence of ventriculomegaly and a lumpy and/or thick pattern of periventricular hyperintensity in patients with MD as compared with the age-matched controls. These white matter abnormalities do not appear to be etiologically specific, but some possible explanations for these frequent findings in MD are discussed. PMID- 3337675 TI - Reflex inhibition of urethral sphincters to permit voiding in paraplegia. AB - When the spinal motoneurons innervating the external sphincter of the urethra cannot be inhibited voluntarily due to lesions of the spinal cord, the normal capacity to relax this physiologic valve during micturition is lost. Even if contractions of the bladder occur, urinary outflow may be completely blocked at the sphincter, leading to distention of the bladder and the risk of urinary infection. A method is described for controllably relaxing the sphincter, which permits free outflow of urine in paraplegic cats. One pudendal nerve is sectioned, paralyzing half of the sphincter, but leaving the experimental animals entirely continent. The motoneurons supplying the other half of the sphincter are inhibited by means of spinal reflexes, eliminating active resistance to urethral flow. The simplicity of this approach suggests that it may prove equally effective in human paraplegia. PMID- 3337676 TI - Optic nerve head drusen and pseudotumor cerebri. AB - A 42-year-old woman presented with a history of headache. Results of funduscopic examination revealed elevated disc margins and bilateral optic nerve head drusen. Lumbar puncture, head computed tomography, and fluorescein fundus angiography results were consistent with the diagnosis of pseudotumor cerebri and coexistent disc drusen. Visual loss was demonstrated by formal perimetry. Headaches were unresponsive to a medical regimen that included prednisone, glycerol, acetazolamide, furosemide, and repeated lumbar punctures. A lumbar peritoneal shunt was performed, with immediate resolution of headache. Optic disc drusen can be associated with pseudotumor cerebri and can lead to diagnostic confusion. PMID- 3337677 TI - Cerebrospinal fluid amino compounds in Parkinson's disease. Alterations due to carbidopa/levodopa. AB - Employing a triple-column ion-exchange/fluorometric procedure, 29 amino compounds, including amino acid neurotransmitters, were measured in lumbar cerebrospinal fluid (CSF) from two groups of patients with idiopathic Parkinson's disease de novo (n = 6) and those who were treated with carbidopa/levodopa (n = 6), and from neurologically normal controls (n = 10). Consideration was given to in vivo and in vitro factors known to influence levels of various CSF constituents. Results showed statistically significant decreases in the levels of gamma-aminobutyric acid, homocarnosine, phosphoethanolamine, and threonine, and elevation of ornithine levels, in the CSF of de novo patients with Parkinson's disease compared with controls. These changes "normalized" following treatment with carbidopa/levodopa. This study suggests that Parkinson's disease may be characterized by defects in specific amino compound metabolic pathways, resulting in central nervous system amino compound imbalances that may contribute to the pathophysiology of this disorder. Carbidopa/levodopa therapy tends to "normalize" these amino compound imbalances. PMID- 3337679 TI - Ambulatory cassette electroencephalography of psychiatric patients. AB - Indications and results of ambulatory cassette electroencephalography obtained on 133 hospitalized psychiatric patients were reviewed. Interictal epileptiform abnormalities were detected in 15 patients (11%), of whom six had an established diagnosis of epilepsy. Actual seizures were recorded in two patients, of whom one had an established diagnosis of epilepsy. Subclinical seizure activity was detected in only one patient, who also experienced overt seizures. Routine screening of psychiatric patients with ambulatory cassette electroencephalography does not seem to be justified, although the test can provide useful adjunctive evidence to support the diagnosis of epilepsy and clarify the nature of suspicious clinical episodes in selected patients. PMID- 3337678 TI - Migrainous stroke. AB - Twenty-two patients with acute migraine-associated stroke were prospectively evaluated; 91% were female, and 23% had a prior history of presumed migrainous stroke. The incidences of major stroke risk factors and mitral valve prolapse were no higher for the study group than for the general population of similar age. Computed tomography, magnetic resonance imaging, or radionucleotide scanning of the brain was performed on all patients, and demonstrated ischemic or hemorrhagic infarction in 12 (55%). Cerebral arteriography revealed abnormalities related to the acute stroke in five (42%) of 12 cases overall, and in four (67%) of six studies performed within 72 hours of stroke onset; one patient (8%) suffered significant complications from arteriography. Although a variety of processes, alone or in combination, may contribute to migrainous stroke, extracranial and/or intracranial vasospasm appears to play a major role in at least some cases. PMID- 3337680 TI - Mutants in Duchenne muscular dystrophy. Implications for prevention. PMID- 3337681 TI - The parental origin of mutations causing Duchenne muscular dystrophy. PMID- 3337682 TI - Mutations in Duchenne muscular dystrophy. PMID- 3337683 TI - Macular grid photocoagulation. An experimental study on the primate retina. AB - We studied the effect of macular grid photocoagulation on the retinal vessels, retina, retinal pigment epithelium, and choroid of normal cynomolgus monkeys. Argon blue-green laser photocoagulation, similar to that employed for treating macular edema due to branch retinal vein occlusion, resulted in a decreased retinal capillary area at both one and five months after treatment. The photoreceptors and retinal pigment epithelium between laser lesions were altered at three days after treatment, but their appearance returned to normal by five months. The significance of these findings is discussed with regard to resolution of macular edema and improvement in vision following grid photocoagulation. PMID- 3337684 TI - Interphotoreceptor retinoid-binding protein levels in subretinal fluid from rhegmatogenous retinal detachment and retinopathy of prematurity. AB - Interphotoreceptor retinoid-binding protein (IRBP) has been detected qualitatively in subretinal fluid associated with rhegmatogenous retinal detachments. We have used a quantitative enzyme-linked immunosorbent assay to determine the IRBP concentrations in 24 fluid specimens collected at retinal reattachment surgery from 22 patients, and from 17 patients who underwent surgery for retinopathy of prematurity with traction detachment. We observed a wide range of concentrations (1 to 176 micrograms of IRBP per milligram of protein). Higher concentrations were found only in fluid from the more recent rhegmatogenous detachments. The lowest concentrations were detected among fluids drained from under rhegmatogenous detachments ranging from five days' to one year's duration. The IRBP concentration in subretinal fluid showed no correlation with visual outcome and may be influenced by IRBP turnover in the vitreous cavity. Most strikingly, none of the 17 samples from patients with retinopathy of prematurity contained detectable amounts of IRBP. PMID- 3337685 TI - Sebaceous gland carcinoma. PMID- 3337686 TI - Ocular albinism. PMID- 3337687 TI - Full-thickness unipedicle flap for lower eyelid reconstruction. AB - We developed a technique for lower eyelid reconstruction using a full-thickness unipedicle flap from the upper tarsal portion of the upper eyelid. The lost tissue is replaced with identical tissue from the ipsilateral upper eyelid. The technique is best suited to shallow defects of the temporal lower eyelid. The levator aponeurosis and Muller's muscle are recessed to avoid upper eyelid retraction. The key to performing this operation is a thorough knowledge of eyelid anatomy and preservation of its microvascular supply. This procedure has produced satisfactory to excellent results in 17 patients and offers the reconstructive surgeon several advantages over other techniques. PMID- 3337688 TI - An interactive model eye for use with ophthalmic instruments. AB - A model eye was found to be a practical and versatile simulator of conditions present in the application of different surgical and diagnostic ophthalmic instruments. It realistically simulated the thermal and acoustic effects of lasers on tissues and thus could be used for teaching and practicing laser therapeutics. The geometric optics were similar to those of the human eye, and realistic conditions of scatter and fluorescence could be created. PMID- 3337689 TI - A lid spatula. AB - A lid spatula was designed to provide a firm base on which to operate, adequate protection of the globe, and an option of fixed or variable traction to the lid. PMID- 3337690 TI - Ophthalmology in West Germany. PMID- 3337691 TI - Intraocular lens power. PMID- 3337692 TI - Transconjunctival approach for intraorbital tumors. PMID- 3337693 TI - Learning the skill of chiastopic direct stereopsis. PMID- 3337694 TI - Corneal damage following the use of the pediculocide A-200 Pyrinate. PMID- 3337695 TI - Misuse of eye drops due to interchanged caps. PMID- 3337697 TI - Case report. Ocular muscle fibrosis following cataract extraction. PMID- 3337696 TI - Case report. Scleral buckling of failed pneumatic retinopexy. PMID- 3337698 TI - Case report. Acute angle closure glaucoma in nonperforating blunt trauma. PMID- 3337699 TI - Case report. Treatment of aggressive epidemic Kaposi's sarcoma of the conjunctiva by radiotherapy. PMID- 3337701 TI - Case report. Anterior and posterior uveal melanomas in one eye. PMID- 3337700 TI - Case report. Cavernous hemangioma of the optic disc. PMID- 3337702 TI - Ophthalmologists find practice marketing services useful. PMID- 3337703 TI - How we deal with our own feelings about blindness. PMID- 3337704 TI - Carotid artery disease. A therapeutic enigma. PMID- 3337705 TI - Acute idiopathic blind spot enlargement. A big blind spot syndrome without optic disc edema. AB - We examined seven patients who had a syndrome of symptomatic monocular blind spot enlargement without optic disc edema. Two patients had previous blind spot enlargement that resolved over several months. The scotoma in each patients was absolute, measured 15 degrees to 20 degrees in diameter, had steep geographic margins, and extended to within 5 degrees to 10 degrees of fixation. Typically, patients had normal visual acuity, color vision, pupillary responses, and ophthalmoscopic findings. Photostress recovery, tested in two patients, was prolonged in the affected eye. Fluorescein angiography showed no abnormalities corresponding to the scotoma. Orbital computed tomographic scans in three patients and visual evoked responses in one patient were normal. Multifocal electroretinography, performed in two patients, showed loss of retinal waveforms in a large region surrounding the optic disc. Our findings suggest that retinal dysfunction produces this big blind spot syndrome, but we do not know its cause. PMID- 3337706 TI - Uremic optic neuropathy. AB - Vision loss progressing over several days, reduced pupil reactions to light, and swollen optic nerves were the clinical features in six patients with severe renal disease manifested by uremia, anemia, and (in four patients) moderately or severely elevated blood pressure. In two patients pale edema of the optic nerve head extended into the macula. One patient with renal transplant rejection was in the early phases of cryptococcal meningitis that went undiagnosed for two weeks. Medical management with hemodialysis was followed by improvement of vision in four patients. In one patient, resumption of oral corticosteroid therapy was followed by improvement in vision. The patient whose vision improved the most rapidly was managed by prompt use of both dialysis and oral corticosteroid therapy. The patient with cryptococcal meningitis did not recover vision. PMID- 3337707 TI - Contrast sensitivity in age-related macular degeneration. AB - Low-contrast charts were used to investigate the possibility that patients with drusen have visual deficits not detected by standard Snellen charts. We compared performance on Regan letter charts between 52 eyes with drusen and Snellen acuity of 20/20 and 27 control eyes. The drusen group read fewer letters than the control group on all of the charts tested. This difference increased as the contrast of the charts decreased. The loss of performance on all of the Regan charts correlated with drusen severity. Twenty-one eyes with drusen and normal Snellen acuity also were tested with a Ginsburg contrast sensitivity chart and compared with age-matched normal controls. The results showed a loss of contrast sensitivity at high spatial frequencies and a loss of peak contrast sensitivity with increasing drusen severity. These results suggest that in patients with drusen, low-contrast charts may be useful for measuring visual loss not detected by standard Snellen charts. PMID- 3337708 TI - Retinoschisis associated with optic nerve pits. AB - Stereoscopic transparencies studied with magnification and projection suggest that the retinal elevation that communicates with optic pits is frequently a schisislike separation of the internal layers of retina. Thirteen of 15 eyes with optic pits and maculopathy fit the schisis pattern. Separation of the outer layers of the retina is a secondary phenomenon that starts in the macula. PMID- 3337709 TI - Corneal toxicity of propamidine. AB - Two patients with Acanthamoeba keratitis developed a corneal abnormality following prolonged treatment with topical 0.1% [corrected] propamidine isethionate. In both instances, withdrawal of drug therapy resulted in a gradual clearing of the keratopathy, with no permanent sequelae. The changes we observed may be confused with those of active Acanthamoeba infection. PMID- 3337710 TI - Clinical signs and medical therapy of early Acanthamoeba keratitis. AB - Several diagnostic signs of Acanthamoeba keratitis have been reported recently. We treated three patients who developed a dendritiform epithelial pattern seen early in the course of Acanthamoeba keratitis that likely represents epithelial infection by Acanthamoeba before any stromal involvement. In these three cases, the early diagnosis of Acanthamoeba keratitis coupled with wide epithelial debridement and medical therapy proved effective in eradicating the protozoan. In two additional cases, Acanthamoeba keratitis was not diagnosed until significant stromal involvement was present. Medical therapy was effective in eradicating the organism in one case, although penetrating keratoplasty was necessary for visual rehabilitation. In the other case, medical therapy was ineffective, as corneal perforation resulted and Acanthamoeba cysts were demonstrated by fluorescent staining in the host corneal button. PMID- 3337711 TI - Cellular proliferation after experimental glaucoma filtration surgery. AB - We used light microscopic autoradiography to determine the time course of cellular incorporation of tritiated thymidine (a correlate of cell division) following glaucoma filtration surgery in seven eyes of four cynomolgus monkeys with experimental glaucoma. Incorporation of tritiated thymidine was detected as early as 24 hours postoperatively. Peak incorporation occurred five days postoperatively and had returned to baseline levels by day 11. Cells incorporating tritiated thymidine included keratocytes, episcleral cells, corneal and capillary endothelial cells, and conjunctival and corneal epithelial cells. Transmission electron microscopy was correlated with the autoradiographic results to demonstrate that fibroblasts were dividing on the corneoscleral margin. These findings have potential clinical implications for the use of antiproliferative agents after filtration surgery. PMID- 3337712 TI - Impaired secretion of type III procollagen in Ehlers-Danlos syndrome type IV fibroblasts: correction of the defect by incubation at reduced temperature and demonstration of subtle alterations in the triple-helical region of the molecule. AB - The amount of type III procollagen secreted by fibroblasts from two patients with type IV Ehlers-Danlos syndrome is reduced to 25% and 20%, respectively, of that of control cells after incubation at 37 degrees C, but reverts to 70% and 110% when cells are incubated at 32 degrees C. The type III procollagen molecules secreted only at the lower temperature are of normal size but apparently contain different mutations which disrupt the triple-helical region and lower the thermal stability of the molecule. These data suggest that subtle mutations in the pro alpha 1(III)-chains produce Ehlers-Danlos syndrome type IV by disrupting the triple-helical region of the molecule, lowering its thermal stability, and thus impairing its secretion. At the lower temperature, stabilization of the defective molecules result in more efficient secretion. This approach may be useful for the characterization of other unstable collagens. PMID- 3337713 TI - Distribution of isoaccepting tRNAs and codons for proline and glycine in collagenous and noncollagenous chicken tissues. AB - The relation between codon usage and tRNA content for proline and glycine, the major constituents of collagen, was studied in two tissues: the magnum of laying hen oviduct and the leg tendons of chick embryo where collagen is produced. Although the relative contents of tRNA(GCCGly) and tRNA(IGGPro) in tendons, as compared to magnum indicate a specialization of the tRNA population for collagen synthesis, the distribution of the preponderant codons in collagen mRNA is correlated but at a lesser extent to that of their cognate tRNAs. PMID- 3337714 TI - Solution and membrane structure of enkephalins as studied by infrared spectroscopy. AB - The backbone conformation of the two opioid pentapeptides Leu5-enkephalin and Met5-enkephalin was studied by the technique of resolution-enhanced infrared spectroscopy. In aqueous solution, the conformation-sensitive amide I bands of the two peptides are identical. The positions of these bands are consistent with the view that in aqueous solution both enkephalins exist as an ensemble of largely unfolded conformers. Interaction of Leu5- and Met5-enkephalins with bilayer membranes of ditetradecylphosphatidylcholine results in a substantial refolding of the peptide backbones. The conformation stabilized by the membrane environment is a hydrogen-bonded turn structure. Conformational transitions in enkephalins induced by a lipid environment may play a role in the specific interactions between these hormones and their receptor sites. PMID- 3337715 TI - Alkylacylglycerol molecular species in the glycosylinositol phospholipid membrane anchor of bovine erythrocyte acetylcholinesterase. AB - Bovine erythrocyte acetylcholinesterase, a glycosylinositol phospholipid anchored membrane enzyme, was digested with phosphatidylinositol-specific phospholipase C and the released glycerol-containing moieties were identified and quantitated. About 96% of the total was alkylacylglycerol, of which sn-1-stearyl-2 stearoylglycerol, sn-1-stearyl-2-oleoylglycerol and sn-1-oleyl-2-stearoylglycerol accounted for 69%, 13% and 10%, respectively. These alkylacylglycerols are in marked contrast to the exclusively diacylglycerol species present in phosphatidylinositol from bovine erythrocyte membranes. This difference suggests that assembly of the membrane anchor of Ebo AChE involves a selected cellular pool of diradylglycerols. PMID- 3337716 TI - Aromatization and 19-hydroxylation of androgens by rat brain cytochrome P-450. AB - The oxidative metabolism of androgens in the rat brain includes aromatization preceded by the requisite 19-hydroxylation. We have examined the transformation of [19-C3H3]androstenedione and [4-14C]testosterone by the semipurified cytochrome P-450 fraction of the rat brain. [19-C3H3]Androstenedione generated tritiated water and formic acid in a ratio of 8 to 1 indicating that 19 hydroxylation in the brain far exceeds that necessary for aromatization. This was confirmed by the results of the 14C-testosterone incubation in which the 14C labeled 19-hydroxy and 19-oxo derivatives which were isolated exceeded the yield of 14C-estrogens by several fold. Thus the rat brain has the capacity to form in situ 19-hydroxylated androgens which are not available to it from the circulation. PMID- 3337717 TI - Histamine H1-receptor in the retina: species differences. AB - Histamine H1-receptors in membranes of the various mammalian retinas were studied by [3H]mepyramine binding assay. Specific [3H]mepyramine bindings to bovine, pig, dog and human retinas were observed with the dissociation constants (KD), 3.8 +/- 1.2 nM, 1.8 +/- 0.6 nM, 2.6 +/- 0.6 nM and 3.0 +/- 0.9 nM, respectively, which were similar to those found in brains. But there was no detectable specific binding in the guinea-pig and rabbit retinas. The number of binding sites (Bmax) ranged from negligible value to 290.7 +/- 51.7 fmole/mg protein(human retina). Some H1-antagonists acted as potent agents in competing with [3H]mepyramine binding to bovine and pig retinas. These results indicated that histamine H1 receptors exist in some mammalian retina and have similar characteristics to those in brain membranes, but they distributes in the wide difference of the binding capacities among the species, while in brain variations were smaller. PMID- 3337718 TI - Arachidonate 15-lipoxygenase from human eosinophil-enriched leukocytes: partial purification and properties. AB - Arachidonate 15-lipoxygenase was purified from human eosinophil-enriched leukocytes after showing that 15-lipoxygenase activity was 100-fold greater in eosinophils than in neutrophils. Partial purification was achieved using ammonium sulfate precipitation, cation-exchange and hydrophobic-interaction chromatography. New evidence is presented suggesting that 15-lipoxygenase has electrostatic and hydrophobic properties distinct from 5-lipoxygenase. In addition, ATP is shown to inhibit, and phosphatidylcholine is shown to stimulate, 15-lipoxygenase, suggesting a regulatory role for these compounds in the lipoxygenation of arachidonic acid. PMID- 3337719 TI - Conformational change on calcium binding by the lipopeptide antibiotic amphomycin. A C.D. and monolayer study. AB - The acidic linear lipopeptide amphomycin is a calcium dependent antibiotic which is thought to bind to carrier lipids such as dolichol monophosphate. The actual role of Ca++ is not definitely established and in this article we have examined the peptides interactions with a range of divalent cations. By CD we have shown that a conformational change is induced by Ca++, Sr++ and Ba++ but not by Mg++, Zn++, Cd++ or Gd+++. Monolayer studies show a decrease in molecular area and an increase in film stability when the subphase contains Ca++. The ensemble of results provides preliminary evidence for the formation of a beta hairpin structure on ion binding (Ka (Ca++) = 2.4 x 10(3)M-1) which could enhance amphomycin's bilayer solubility. PMID- 3337720 TI - Non-cyclic photoreductive carbon fixation in photosynthesis. Light and dark transients of the glycerate-3-P special pair. AB - It is demonstrated that carbon fixation in photosynthesis is regulated in two kinetically coupled pathways involving the specialized pair of non-equivalent, enzyme-bound glycerate-3-P (3-PGA) molecules obtained from ribulose 1,5 bisphosphate (RuBP) carboxylation in the light. A non-cyclic pathway is suggested (reaction 2) for the direct biosynthesis of sucrose from the 3-PGA obtained from C-3, C-4 and C-5 of the six-carbon carboxylation adduct. Concomitant to the appearance of sucrose as the principal product, the Mg2+-bound 3-PGA molecule formed from C-1, C-2 and C-2' of the C6 intermediate is released and subsequently reduced in regenerating the RuBP. It is proposed that the nocturnal inhibitor, 2 carboxyarabinitol-1-phosphate (1-PCA) is obtained from a condensation of 3-PGA and glyceraldehyde. PMID- 3337721 TI - Expression of epidermal growth factor receptor proto-oncogene mRNA in regenerating rat liver. AB - The expression of EGF receptor mRNAs in regenerating rat liver was measured using two nonoverlapping cDNA probes for the human gene from a highly conserved region. These probes (pE7 and pE62) both hybridized to RNA species of 10 and 6 kb. The 10 and 6 kb RNA species were shown to decrease in the first 12 hours after partial hepatectomy. However, significant increases above control levels were noted at 24h and 72h. The level of alpha-actin mRNA increased as has been previously reported. These results suggest that a transcriptional and/or a posttranscriptional regulatory mechanism exists in regenerating rat liver with respect to EGF receptor gene expression. PMID- 3337722 TI - Localization of the active center of microsomal cytochrome P-450. AB - To solve the problem of localization of the active center of cytochrome P-450 in microsomal membranes, new bifunctional compounds (I-IV), which contain pyridine radical, aliphatic chain of variable length and diphosphonic acid ("floating" molecules) have been applied. These compounds inhibit oxidation and binding of the substrates of cytochrome P-450 (aminopyrine and aniline), inhibition being of a competitive character. Measurements of distribution coefficients between water and membranes of microsomes and liposomes from egg phosphatidylcholine evidence that the microsomal proteins are necessary for providing effective interaction of I-IV with microsomal membrane. The 1H-NMR method has demonstrated compounds to be incorporated into lipid bilayer so that the non-polar part is in the inner membrane volume. The results obtained confirm our previous conclusion (Krainev A.G., Weiner L.M., Alferyev I.S., Slynko N.M. (1985) Biochim. Biophys. Acta, 818, 96-104) about localization of the active center of microsomal cytochrome P-450 at the depth of approximately 18 A from the hydrophilic surface of a membrane. PMID- 3337723 TI - Ligand-dependent maintenance of ethanol-inducible cytochrome P-450 in primary rat hepatocyte cell cultures. AB - Administration of ethanol, dimethylsulphoxide, 2-propanol or imidazole to rats caused 2-7-fold increases in the level of hepatic ethanol-inducible cytochrome P 450 (P-450j), without any concomitant enhancement of corresponding mRNA. All the compounds were able to stabilize P-450j in hepatocyte cultures for at least three days, whereas P-450j mRNA rapidly disappeared from the cultures. A correlation was reached between the concentration of Me2SO, ethanol and 2-propanol necessary to maintain P-450j in the cell cultures and their binding affinities to the enzyme. It is suggested that the ligand-bound form of P-450j in the hepatocytes is protected from degradation. PMID- 3337724 TI - Adrenocortical pregnenolone-binding protein: identification and antibody development. AB - Pregnenolone-binding activity isolated from the cytosol of the guinea pig adrenal cortex appears to correspond to a Mr 34,000 protein when examined by SDS polyacrylamide gel electrophoresis during different stages of purification. To verify this finding the Mr 34,000 protein band was eluted from the SDS gel and used to generate a polyclonal antibody. Immobilized anti 34,000 IgG on protein A Sepharose was found to extract pregnenolone-binding activity from solution in contrast to pre-immune IgG and an antibody raised against a Mr 30,000 protein isolated simultaneously. In addition, protein eluted from the protein A-anti 34,000 IgG complex exhibited the expected molecular weight of 34,000 when examined on an SDS gel. These results, thus, confirm that the pregnenolone binding protein is indeed a protein of Mr 34,000. PMID- 3337725 TI - Similarity between the estrogen receptor and the DNA-binding domain of the tetracycline repressor. AB - The amino-terminus region of tetracycline (tet) repressors contains a helix-turn helix structure that binds to DNA. A computer-based comparison of a residues 18 61 of the tet repressor, which contains this DNA-binding domain, with a residues 304-347 of the human estrogen receptor (ER) yields a score that is 6.7 standard deviations higher than that obtained with 2,500 comparisons of randomized sequences of these segments. The probability of getting this score by chance is less than 10(-11). This part of the ER could be important in nuclear actions of ER in target tissues. PMID- 3337726 TI - Identification of an acid-lipase in human serum which is capable of solubilizing glycophosphatidylinositol-anchored proteins. AB - A lipase has been identified in human serum which can convert the membrane form of the variant surface glycoprotein of Trypanosoma brucei to a water soluble form. The conversion can be monitored by loss of [3H] myristic acid incorporated into the diacylglycerol of the glycophosphatidylinositol membrane anchor of the protein, but does not lead to the exposure of the antigenic determinant in the polar head group of the glycolipid. The serum lipase is a glycoprotein, and is optimally active at pH 5.4. Treatment at 62 degrees for one hour does not inactivate the enzyme, which is inhibited by chelating agents. PMID- 3337728 TI - Renotropic activity of lutropin: direct stimulation of DNA synthesis of cultured rat renal cortical cells. AB - Two differently purified ovine lutropin (LH) preparations were studied to see if they stimulated [3H] thymidine incorporation into cultured rat renal cortical cells. Both preparations showed a dose-dependent (0.11-1 ng/ml), time-dependent (peaking at 18 h), serum-dependent (7.5% of fetal calf serum or 10% castrated hypo-physectomized rat serum) renotropic effect. Ovine TSH and FSH failed to mimic this specific, renotropic effect. We concluded that LH directly stimulates renal DNA synthesis in cooperation with other serum factor's. PMID- 3337727 TI - S-adenosyl-L-methionine protects the hippocampal CA1 neurons from the ischemic neuronal death in rat. AB - We investigated the effect of S-adenosyl-L-methionine (SAMe) on the prevention of the delayed neuronal death in rats subjected to transient and brief forebrain ischemia. As the results, SAMe dose-dependently protected the hippocampal CA1 neurons from degeneration and necrosis, whose effect was suppressed by simultaneous administration of S-adenosyl-L-homocysteine, a potent inhibitor in transmethylation. No protective effect was observed in CDP-choline, phosphatidylcholine and L-methionine. Therefore, it is necessary for the prevention of the delayed neuronal death to enhance cerebral SAMe level and to activate transmethylation using SAMe as a methyl donor in postischemic brain. PMID- 3337729 TI - Identification of [hydroxyproline3]-lysyl-bradykinin released from human plasma protein by kallikrein. AB - [Hydroxyproline3]-lysyl-bradykinin [( Hyp3]-Lys-BK), a new kinin was isolated, besides lysyl-bradykinin (Lys-BK), from the reaction mixture of human plasma protein Cohn's fraction IV-4 with hog pancreatic kallikrein. The liberated kinins were isolated by procedures including ethanol extraction, Sephadex G-15, CM cellulose and reverse-phase high performance liquid chromatography (HPLC) and quantitated by radioimmunoassay. On HPLC, two peaks of immunoreactive kinins emerged. Peak 1, an unknown kinin proceeded to Peak 2 which had an identical retention time to that of Lys-BK. The amino acid sequence of the unknown Peak 1 proved to be Lys-Arg-Pro-Hyp-Gly-Phe-Ser-Pro-Phe-Arg, or [Hyp3]-Lys-BK, and Peak 2 Lys-BK. The ratio of the amounts of two kinins thus formed were [Hyp3]-Lys-BK 25 +/- 4% and Lys-BK 75 +/- 4%. The existence of [Hyp3]-Lys-BK suggests a presence of a new kininogen, containing [Hyp3]-Lys-BK in human plasma protein, possibly undergone post-translational modifications. PMID- 3337730 TI - Down regulation of c-myc, c-fos and erb-B during estrogen induced proliferation of the chick oviduct. AB - Oncogenes c-myc, H-ras, c-fos and erb-B were constitutively expressed in immature chick oviduct withdrawn from estrogen administration for 2.5 weeks after 10 d of primary estrogen stimulation. Following secondary estrogen stimulation of the withdrawn chicks, synthesis of egg white proteins is rapidly induced and remaining non-functioning tubular gland cells are stimulated to proliferate with a doubling time of 24 h. During first 12 h of secondary estrogen stimulation, H ras mRNA levels doubled and did not increase further at 24 h and 48 h. The steady state levels of c-myc, erb-B and c-fos mRNA decreased 24 h following secondary estrogen stimulation. The levels of these oncogene RNAs in oviduct were similar at 48 h following secondary estrogen stimulation to those from immature chicks administered 10 d of primary estrogen stimulation. Thus elevated expression of c myc and c-fos mRNA does not appear to be necessary components for sustained estrogen induced cell proliferation in the chick oviduct. PMID- 3337732 TI - Stereochemistry in drug action. Proceedings of the Third Biochemical Pharmacology Symposium. Oxford, 23-24 July 1987. PMID- 3337731 TI - Primary structure of nonspecific crossreacting antigen (NCA), a member of carcinoembryonic antigen (CEA) gene family, deduced from cDNA sequence. AB - A cDNA containing the entire coding region for a member of carcinoembryonic antigen (CEA) gene family has been cloned from cDNA library of HLC-1 cells by immunochemical screening with the antibody specific to nonspecific crossreacting antigen (NCA). The cDNA encodes a precursor form of a polypeptide consisting of a 34-residue signal sequence, a 108-residue N-terminal (N-) domain, a 178-residue domain (NCA-I domain) and a 24-residue domain rich in hydrophobic amino acids (M domain). Each domain has a distinct but homologous amino acid sequence to that of the corresponding domain of CEA. Unlike the coding sequences, the 3'-untranslated sequences differ markedly in the NCA and CEA cDNAs facilitating the preparation of probes that will discriminate between nucleotide sequences for CEA and NCA. PMID- 3337733 TI - Chirality and cytochrome P-450: a perspective. PMID- 3337734 TI - The influence of the ethyl group on the conformational flexibility of aminoglutethimide. PMID- 3337735 TI - Enantiomers of cyclophosphamide and iphosphamide. PMID- 3337736 TI - Stereoselective glutathione conjugation of the separate alpha-bromoisovalerylurea and alpha-bromoisovaleric acid enantiomers in the rat in vivo and in rat liver subcellular fractions. AB - Glutathione (GSH) conjugation of the separate alpha-bromoisovalerylurea (BIU) enantiomers was studied in the rat. Administration of (R)-BIU resulted in excretion of a single glutathione conjugate in bile (IU-S-G/I) and a single mercapturate in urine (IU-S-MA/B). The other enantiomer, (S)-BIU, was exclusively metabolized to the other diastereomeric conjugates, IU-S-G/II and IU-S-MA/A. Thus, the conjugation of BIU with glutathione was completely stereospecific. Both the GSH conjugate and mercapturate derived from (R)-BIU were excreted two to three times more rapidly than their diastereomeric (S)-BIU counterparts. The enantiomers did not influence each others metabolism as reflected by identical metabolite excretion rates when the BIU enantiomers were administered either separately or as the racemic mixture. A similar rate difference for GSH conjugation of the separate BIU enantiomers was observed in incubations with rat liver cytosol as source of GSH transferases, suggesting that the stereoselectivity in vivo was due to glutathione conjugation properly. Similar results were obtained with a rat liver microsomal fraction, indicating that microsomal GSH transferases are active towards BIU and have a similar stereoselectivity as the cytosolic enzymes. Comparison of the GSH conjugation of BIU with that of its analogue alpha-bromoisovaleric acid (BI, which lacks the amide-linked urea group) revealed an opposite stereoselectivity: while (R)-BIU was conjugated faster than (S)-BIU, the (R) enantiomer of the acid was conjugated more slowly than (S)-BI. The alpha-bromocarbonyl compounds BI and BIU present a new type of substrate for the GSH transferases and allow studies of these enzymes in intact organisms as well as investigations on the stereoselectivity of GSH conjugation. PMID- 3337737 TI - Stereoselective 4-hydroxylation of debrisoquine in Nigerians. PMID- 3337738 TI - In vivo protection against soman toxicity by known inhibitors of acetylcholine synthesis in vitro. AB - Soman inhibits the enzyme acetylcholinesterase, essentially irreversibly, producing an accumulation of acetylcholine (ACh) which is responsible for many of its toxic effects. Current approaches to treatment include: (1) atropine, a muscarinic receptor blocker; (2) pyridine-2-aldoxime methylchloride (2-PAM), an enzyme reactivator; and (3) carbamate protection of the enzyme. However, no fully satisfactory regimen has been found, primarily because of the rapid aging process. In this study, compounds known to inhibit ACh synthesis in vitro were evaluated in combination with atropine and 2-PAM so as to assess their potential utility in protection against soman toxicity in rats. Acetylsecohemicholinium (100 micrograms/kg, i.c.v.t., 30 min prior to soman), an inhibitor of high affinity choline uptake (HAChU) and cholineacetyltransferase (ChAT) activity in vitro, enhanced the protective effects of atropine and 2-PAM, reducing the mortality within the first 2 hr following soman. N Hydroxyethylnaphthylvinylpyridine (NHENVP), a quaternary ChAT inhibitor (1.7 mumol/kg, i.m.), significantly reduced the overall percent mortality due to soman from 80% to 20%. The compound was most effective when administered 2-3 min prior to soman and was effective only by the intramuscular route. N-Allyl-3 quinuclidinol, a potent HAChU inhibitor (1 mumol/kg, i.m.) was the most effective quinuclidine analog evaluated, also reducing the percent mortality for a 24-hr period. Unlike NHENVP, it was most effective when given 30-60 min prior to soman. It is suggested from the data that compounds that disrupt presynaptic ACh synthesis in vitro may prove effective in treating organophosphate poisoning. The results demonstrate interesting differences among the compounds studied and provide insight for the design of protectants against soman toxicity. These findings further underscore the need to examine the structure activity and pharmacokinetic properties of these compounds, i.e. comparison of routes of administration, dose-response relationships, and time to effect. PMID- 3337739 TI - Structural features of potent inhibitors of rat kidney histamine N methyltransferase. AB - Three antimalarial drugs amodiaquine, quinacrine and chloroquine were compared side-by-side with the antiseptic agent chlorhexidine and the neuromuscular blocker alcuronium for their capacity to competitively inhibit in vitro the activity of the enzyme histamine N-methyltransferase (HMT) from rat kidney over the concentration range 10(-3)-10(-8). Amodiaquine was clearly the most potent HMT inhibitor followed by quinacrine, chlorhexidine, alcuronium and chloroquine. Investigation of the structure-activity relationships by examining space-filling models revealed marked similarities in the conformations of the arrangement of three N atoms in histamine and in each of the compounds tested. PMID- 3337740 TI - Inhibition of phagocyte chemotaxis by uteroglobin, an inhibitor of blastocyst rejection. AB - Uteroglobin, a steroid-dependent secretory protein first discovered in the rabbit uterus during early pregnancy, is a potent phospholipase A2 inhibitor. We found that uteroglobin also inhibited human and rabbit phagocyte chemotaxis in response to formyl peptide attractants in a dose-dependent manner. Half-maximal inhibition was at 1.2 microM. Uteroglobin did not compete with a formyl peptide for its receptor but inhibited internalization of radiolabeled formyl peptide. Uteroglobin appears to inhibit chemotaxis by a mechanism different from that of dansylcadaverine, a well studied inhibitor of endocytosis. Unlike dansylcadaverine, uteroglobin did not have any effect upon the synthesis of phosphatidylcholine or phosphatidylinositol. It is suggested that uteroglobin may protect trophoblastic cells from the defense system of the host not only by binding to antigenic determinants of embryonic cells but also by impairing migration of phagocytes, one of the primary components of the immune defense system. These results may explain why embryonic cells do not elicit an inflammatory response in the uterine endometrium during pregnancy. PMID- 3337741 TI - Dialuric acid autoxidation. Effects of transition metals on the reaction rate and on the generation of "active oxygen" species. AB - The autoxidation of dialuric acid, a process which is believed to be of crucial importance in the diabetogenic action of alloxan, was found to be strongly catalysed by copper, iron and manganese. Superoxide radical and hydrogen peroxide were generated in both the uncatalysed and the metal-catalysed reactions. In contrast, hydroxyl radical was formed during dialuric acid autoxidation only in the presence of added iron salts. Production of the latter radical was strongly inhibited by catalase but only weakly by superoxide dismutase, implying that the metal-catalysed Haber-Weiss reaction is of comparatively little importance in hydroxyl radical generation from dialuric acid. PMID- 3337742 TI - Comparative effects of antithrombitic and antimycotic N-substituted imidazoles on rat hepatic microsomal steroid and xenobiotic hydroxylases in vitro. AB - N-Substituted imidazoles have been shown to be potent inhibitors of microsomal mixed-function oxidase activities in vitro and in vivo. In the present study the effects of two antithrombitic (dazmegrel and dazoxiben) and four antimycotic (ketoconazole, econazole, miconazole and clotrimazole) imidazoles on microsomal cytochrome P-450-mediated steroid and xenobiotic hydroxylases were studied in vitro. Despite the presence of the N-substituted imidazole moiety, the antithrombitic agents were essentially non-potent as inhibitors of all of the oxidase activities evaluated. In contrast, the antimycotic drugs were potent inhibitory compounds. Binding studies revealed that all six imidazoles elicited type II optical difference spectra and exhibited relatively high affinity for ferricytochrome P-450 in microsomal suspensions (Ks range 0.26-0.73 microM for the antimycotic agents and 6.5 microM and 21 microM for dazmegrel and dazoxiben, respectively). The structural feature that the antithrombitic compounds share is a carboxylate function so that, at physiological pH, less than 1% of the drug would be present in the unionised form. This functionality is absent from the structures of the antimycotic agents which possess much greater hydrophobic character. Even though the antithrombitic imidazoles elicit type II binding interactions of quite high affinity it would appear from this study that significant inhibition potency does not necessarily follow. The present findings also suggest that interesting differences exist between the active site binding regions in the cytochrome P-450 that catalyse thromboxane synthetase activity and those involved in microsomal drug oxidation. Inhibitor hydrophobicity is clearly an important factor in the inhibition of microsomal cytochromes P-450 whereas effective thromboxane synthetase inhibitors may be quite hydrophilic at physiological pH. PMID- 3337743 TI - Mechanisms of cross-resistance to methotrexate and 5-fluorouracil in an A2780 human ovarian carcinoma cell subline resistant to cisplatin. AB - Some properties of the human ovarian carcinoma line A2780 and a subline three times more resistant than the parent line to cisplatin are compared in this report. The rates of uptake and release of cisplatin were similar in the two cell lines. Resistance to cisplatin was associated with: (a) cross-resistance to 5 fluorouracil and methotrexate; (b) a 2.5-fold increase in thymidylate synthase, as measured by both enzyme activity and the capacity to complex 5 fluorodeoxyuridylate; and (c) an increase in the intracellular pools of 5,10 methylenetetrahydrofolate and tetrahydrofolate. These data suggest that cross resistance to 5-fluorouracil and methotrexate in A2780 cells may be a consequence of increases in their respective target enzymes. PMID- 3337744 TI - Inhibition of chicken liver 5-aminoimidazole-4-carboxamide ribonucleotide transformylase by 5,8-dideaza analogues of folic acid. AB - A series of fourteen 5,8-dideaza analogues of folic and pteroic acids was evaluated for inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (AICAR TFase) from chicken liver. Of the 5,8-dideaza folate derivatives studies, 10-oxa-5,8-dideazafolic acid was the most potent inhibitor. The addition of one L-glutamate moiety to the gamma-carboxyl group caused a 6- to 7-fold reduction in Ki in three instances. Two compounds devoid of an L-glutamate were 4- to 6-fold less inhibitory than their parent counterparts possessing one L glutamate residue. PMID- 3337745 TI - Metabolic activation of environmental carcinogens and mutagens by human liver microsomes. Role of cytochrome P-450 homologous to a 3-methylcholanthrene inducible isozyme in rat liver. AB - The metabolic activation of procarcinogens and promutagens by human liver microsomal cytochrome P-450 has been investigated by means of a newly developed method measuring the induction of umu gene in Salmonella typhimurium TA1535/pSK1002 [T. Shimada and S. Nakamura, Biochem. Pharmac. 36, 1979 (1987)]. The chemicals examined were aflatoxin B1 (AFB1), eight carcinogenic heterocyclic aromatic amines isolated from protein and amino acid pyrolysates, and 2 aminoanthracene. Liver microsomes from six patients catalyzed the metabolic activation of these chemicals; 2-amino-3,5-dimethylimidazo[4,5-f]quinoline (MeIQ) and AFB1 were most actively bioactivated, followed by 2-amino-3-methylimidazo[4,5 f]quinoline (IQ), 2-aminoanthracene (2-AA) and 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline. At least two forms of human cytochrome P-450 may be involved in the activation of these procarcinogens. This suggestion was supported by the following lines of evidence: (a) addition of non-ionic detergent Emulgen 913 to the incubation mixture caused a more profound inhibition of microsome-catalyzed activation of AFB1 than of MeIQ, IQ and 2AA, (b) 7,8-benzoflavone stimulated the activation of AFB1 by about 2.5-fold, whereas it inhibited significantly the reactions with MeIQ, IQ and 2AA, and (c) polyclonal antibodies against a 3 methylcholanthrene-inducible form of rat cytochrome P-450 (P-450d) caused a marked inhibition of the metabolic activation of MeIQ, IQ and 2-AA by human liver microsomes though they did not show any effects on the microsomal activation of AFB1. Data are also presented showing that none of the reactions catalyzed by human liver microsomes were inhibited by antibodies to a phenobarbital-inducible form of rat cytochrome P-450 (P-450b). These results suggest that the human cytochrome P-450 isozyme that is immunochemically similar and, thus, homologous to rat P-450d plays a major role in the metabolic activation of several procarcinogens examined, and that the activation of AFB1 is catalyzed by another and, possibly, not phenobarbital-inducible form(s) of human cytochrome P-450. PMID- 3337746 TI - Role of nonprotein thiols in enzymatic reduction of 2-nitroimidazoles. AB - The role of nonprotein thiols (NPSH) in the enzymatic reduction of the nitro function in 2-nitroimidazoles (2-NI) has been investigated. The addition of NPSH has been shown previously to protect cells from the hypoxic cytotoxicity of 2-NI, whereas depletion of NPSH enhances the hypoxic cytotoxicity. In this report, we have investigated the effects of thiol depleting agents, N-ethylmaleimide (NEM) and diethyl maleate (DEM), on the enzymatic reduction of the nitro group. Cytosolic and microsomal fractions of rat hepatic tissue and xanthine oxidase were employed as sources of nitro reductases. Addition of NPSH caused an enhancement in the reduction of the nitro group of 2-NI; cysteine was significantly more effective than glutathione (GSH) in stimulating the enzymatic reduction. The reduction of the nitro function was decreased markedly in the presence of NEM or DEM. Addition of cysteine or GSH reversed the inhibition with NEM. Both NEM and DEM also attenuated the enhancement of reduction observed after the addition of NPSH. These results suggest that the addition of NPSH facilities the reduction of the nitro function to the reduced intermediates that may be inactivated by an excess of NPSH, whereas the depletion of NPSH allows the accumulation of the toxic nitro radicals causing increased cytotoxicity. PMID- 3337747 TI - The effect of hyperthermia on ornithine decarboxylase activity in different rat tissues. AB - Hyperthermia produced a decrease of ornithine decarboxylase activity in different tissues of adult rats. The fall in ornithine decarboxylase was dependent on time of exposure and temperature. The decay of ornithine decarboxylase activity in liver, brain, kidney, heart, spleen and testes was rather similar. The t1/2 for liver ornithine decarboxylase determined by the hyperthermic treatment (40 degrees ambient temperature) was 20 min. Ornithine decarboxylase activity was recovered in all tissues exposed to the hyperthermic shock after a period of 4 hours, although the degree of recovery was dependent on the type of tissue. The effect that hyperthermia produces on ornithine decarboxylase activity in rats could be related to an inhibition in the synthesis of active enzyme rather than to a specific degradation or inactivation of ornithine decarboxylase molecule. PMID- 3337748 TI - Felodipine-induced inhibition of polymorphonuclear leukocyte functions. AB - Felodipine inhibits fMet-Leu-Phe or ionophore A23187-induced exocytosis in rabbit peritoneal polymorphonuclear leukocytes (PMNs), in the concentration range 1-50 microM. Activation of the metabolic burst, and migration of PMNs towards fMet-Leu Phe are equally inhibited by felodipine in the same concentration range. The effect is not due to blocking of calcium channels in the plasma membrane, because the degree of inhibition remains the same when Ca2+ is omitted from the medium. Felodipine interferes with ionophore A23187-induced association of 45Ca with the PMN but this interference occurs at lower concentrations than the inhibition of exocytosis. Hypotonic hemolysis of erythrocytes is inhibited by felodipine; maximal protection against hemolysis occurs at a concentration of 50 microM felodipine. It is suggested that at least a part of the inhibiting effect on PMN functions might be due to an anesthetic-like membrane effect of felodipine. PMID- 3337749 TI - Reversal of the anti-inflammatory effects of dexamethasone by the glucocorticoid antagonist RU 38486. PMID- 3337750 TI - Androgen catabolism and excretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats. PMID- 3337751 TI - Worksite hypertension control: development and application. PMID- 3337752 TI - How management and nurses perceive occupational health nursing. PMID- 3337754 TI - Occupational health hazards--a famine relief camp in Ethiopia. PMID- 3337753 TI - Management of female incontinence with Kegel exercises. PMID- 3337755 TI - Treating high blood pressure. Can it cause depression? PMID- 3337756 TI - Amniotic fluid concentrations of fibronectin and intra-amniotic infection. AB - A cohort study with four groups of pregnant women was designed to evaluate if a decrease in the concentration of fibronectin (FN) in amniotic fluid plays a role in the genesis of premature rupture of the membranes (PROM) and/or intra-amniotic infection: group 1, 15 patients with PROM and intra-amniotic infection; group 2, 15 patients with PROM but without intra-amniotic infection; group 3, 15 patients with preterm labor without PROM or intra-amniotic infection; and group 4, 15 patients who underwent elective amniocentesis for fetal lung maturity studies. No significant differences in amniotic fluid concentrations of FN among any of the four groups was observed (F = 0.146; P = 0.931). These results suggest that a deficiency of FN in amniotic fluid is not a critical factor in determining which patients may be affected by PROM or which of them will develop an intra-amniotic infection. PMID- 3337757 TI - Serum ferritin levels in preterm infants after multiple blood transfusions. AB - We have examined the effect on iron stores of blood transfusions given to premature neonates during hospitalization in the neonatal intensive care unit as reflected by serum ferritin levels measured for 6 months after discharge. Premature infants who were transfused with more than 100 ml packed cells (group D; n = 11) had higher ferritin levels for a longer period than premature infants who were transfused with smaller volumes (group c; n = 9) or premature and mature infants who were not transfused at all (group B; n = 24 and group A; n = 21, respectively). At 4-5 months the serum ferritin levels in group D (489.8 +/- 132.1 micrograms/L; mean +/- SEM) were significantly higher (P less than 0.001) than those of the other groups. The level of group A term infants (77.5 +/- 12.5 micrograms/L) was higher than those of group B premature infants who did not receive a blood transfusion (33.0 +/- 7.1 micrograms/L) or group C who received less than 100 ml (36.5 +/- 8.8 micrograms/L packed red blood cells. However, these differences were not statistically significant. Our data demonstrate that very-low-birthweight infants who receive a large volume of packed cells during hospitalization may accumulate iron stores sufficient for red cell production during the first 6 months of life. Administration of large amounts of supplemental iron, in such cases, may be curtailed. PMID- 3337758 TI - Prenatal diagnosis and perinatal management of frontoethmoidal meningoencephalocele. AB - Frontoethmoidal meningoencephaloceles (FEM) are exceedingly rare in the western hemisphere, Australia, and Europe with an estimated frequency of 1 in 40,000 live births. Among the inhabitants of Thailand, Burma, Malaysia, Indonesia, and parts of the Soviet Union, however, the frequency is as high as 1 in 5000, accounting for 15% of all neural tube defects (NTD). Normal maternal serum alpha-fetoprotein (MSAFP) values usually will be found in these cases since most encephaloceles are closed, skin covered defects. Correct interpretation of the sonographic findings is crucial in establishing a diagnosis as well as giving prognostic and recurrence risk information. To our knowledge, this is the first reported case of prenatally diagnosed FEM. Perinatal management, differential diagnosis for disorders associated with this malformation, and epidemiologic information regarding this rare condition are discussed. It is anticipated that the prenatal sonographic findings may be applied to establish this diagnosis in similarly affected fetuses. PMID- 3337759 TI - Intermamillary indices in premature infants. AB - The internipple distance and its relationship to gestational age has not been studied in infants born in the United States. One hundred and thirty-three newborns between 25 and 40 weeks gestation showed progressive increase in the internipple distance with increasing gestational age. The internipple index stays constant during various gestational ages. The internipple index greater than 28% (greater than 2 SD) at any gestational age or during immediate postnatal age should be flagged to look into widely spaced nipples. Extrauterine growth of internipple distance is similar to that of intrauterine growth. PMID- 3337760 TI - The value of the leukocyte esterase test in diagnosing intra-amniotic infection. AB - This communication examines the diagnostic value of the leukocyte esterase activity (LEA) test in the detection of intra-amniotic infection. Amniotic fluid from 171 consecutive patients with premature rupture of membranes (n = 149) and preterm labor (n = 22) was obtained through amniocentesis. Gram stain, bacterial and mycoplasma cultures, and LEA tests were performed. The LEA had a sensitivity of 19%, a specificity of 86.7%, a positive predictive value (PPV) of 42.3% and a negative predictive value (NPV) of 67.6% in the prediction of a positive amniotic fluid culture (prevalence of positive cultures = 33.9%). The Gram stain had a sensitivity of 36.2%, specificity of 94.7%, PPV of 77.8%, and NPV of 74.3%. When both tests were combined, a significant increase in sensitivity to 50% was observed. This was associated with a drop in specificity to 81.4%. There was a correlation between the number of white blood cells in the amniotic fluid and the result of the LEA test. A positive LEA assay was associated with an increased likelihood of postpartum endometritis, but not with clinical chorioamnionitis or neonatal infectious morbidity. PMID- 3337761 TI - A validation of a scoring system to evaluate the condition of transported very low-birthweight neonates. AB - A scoring system was developed to objectively evaluate the condition of transported preterm infants. The "transport score" used five variables: blood glucose, blood pressure, pH, pO2, and temperature. Each variable was scored 0, 1, or 2, with a total achievable score from 0 to 10. Twenty-one matched pairs of infants included one infant who lived and one who died. The transport scores upon admission of infants who lived was significantly greater than the scores of those who died (P less than 0.01). Scores less than eight were predictive of death (sensitivity 62%, specificity 81%). The system was then applied prospectively to 106 different infants after stabilization by the hospital-of-origin (pre transport) and upon admission to the neonatal intensive care unit (post transport). Although 75 (76%) of the 99 surviving infants had both stabilization and admissions scores of eight or more, only 2 (29%) of the 7 infants who died had both scores of eight or more. Of 85 infants with a stabilization score of eight or greater, only 3 (3.5%) died, while of 21 infants with stabilization scores less than eight, 4 (19%) died. Similarly, of 90 infants with an admission score of eight or more, only 4 (4.4%) died, while of 16 with an admission score of less than eight, 3 (19%) died. We conclude that transport scores provide a valid indication of the condition of preterm infants and may be used to provide quality assurance for stabilization and transport efforts. PMID- 3337763 TI - The need to discontinue the use of the term "accident" when referring to unintentional injury events. AB - Inconsistencies in the common usage of the words "accident" and "injury" are examined. The practical difficulties in applying some commonly accepted definitions are illustrated. It is shown how common notions of "accident" are not supported by the facts and are counter-productive to preventive measures. It is argued that the phrase "injury control" provides a more comprehensive perspective of the problem than the phrase "accident prevention", but its use also has disadvantages. It is concluded that health professionals should discontinue using the term "accident" and associated phrases, when referring to unintentional injury events. PMID- 3337762 TI - Tolerance of fat emulsions in very-low-birthweight neonates. Monitoring of plasma lipid concentrations. AB - Tolerance to parenterally administered fat emulsions was studied in 45 normally grown neonates ranging from 820 to 1550 gm in birthweight, from 27 to 34 weeks in gestational age, and from 2 to 10 days postnatal age. Concentrations of total lipids, free glycerol, true triglycerides, free fatty acids, and cholesterol in plasma were studied over an 8-day period. The aim was to determine whether the concentrations of any one lipid fraction could be used to predict those of other fractions. With 650 pairs of data being correlated, the best correlation coefficients were obtained between total lipids and triglycerides (r = 0.67), total lipids and cholesterol (r = 0.63), free glycerol and free fatty acids (r = 0.55), total lipids and free fatty acids (r = 0.54), and triglycerides and free fatty acids (r = 0.50). Although all correlation coefficients were highly significant statistically (P less than 0.001), the very large standard errors precluded using any of these relationships to make clinical predictions. Problems and limitations of currently available techniques are discussed in order to provide a lead for further research. PMID- 3337764 TI - Developing a risk/cost framework for routing truck movements of hazardous materials. AB - As the United States continues to increase its dependence on industrial technologies which require hazardous materials and generate hazardous wastes, concern is mounting over the safe transport of hazardous cargo. It is estimated that 1.5 billion tons of hazardous cargo are moved through the nation's transportation systems (excluding pipeline), with truck as the primary mode of transport. Because of the dynamic nature of exposure to the population and environment associated with the transport of hazardous cargo, it is important to develop an accurate representation of this type of transport risk, and to structure a framework for designating a permanent set of shipping routes based on optimizing across risks and costs. This paper describes a methodology which has been developed that incorporates risk and cost into a framework for optimizing the routing of truck movements of hazardous materials. Considerable attention is focused on the risk estimation part of this process, as this is a subject of much uncertainty and of considerable significance to policymakers. The resulting methodology is applied in a regional setting to illustrate its use as an analysis tool. Enhancements to the model structure and extensions beyond the truck routing problem are also discussed. PMID- 3337765 TI - A three-year prospective study of rearrests for driving under influence of alcohol or drugs. AB - Fifty drunken drivers and 50 drivers with high blood drug concentrations arrested during the first four months of 1983 were selected for a study of rearrests for driving under influence of alcohol or drugs. Of the drugged drivers selected, 32 had been driving with high blood concentrations of diazepam (greater than 1.0 microM). 50% of these drivers were rearrested during the subsequent three years. The rearrest rate was low (6%) among those who had been driving with high blood concentrations of amphetamine (greater than 2.0 microM) or THC (greater than 0.010 microM). Among the drunken drivers arrested (BAC greater than 0.05%), the rearrest rate was 20%. The drivers were mostly rearrested for driving under the influence of alcohol. PMID- 3337766 TI - Driver behavior at flashing-light, rail-highway crossings. AB - The risk of accident at flashing-light, rail-highway crossings has been found to be ten times higher than at crossings equipped with barriers. The purpose of the present investigation was to study driver behavior in rail-highway crossings and to relate measures of driver behavior to variables believed to be associated with increased risks of accident. About 2,000 drivers were observed in 16 different crossings with driver head movements as the major dependent variable. This variable exhibits wide variability among drivers as well as satisfactory interobserver reliability. The results showed that many drivers turned their head to look for trains in rail-highway crossings although the crossings were equipped with flashing warning lights. However, fewer drivers looked when the visibility was restricted, a factor that is associated with increased risk of accident, and in crossings with few trains per day. The conclusion from the present study is that flashing-light crossings should be designed in a way that redundant information about approaching trains should be easily available to the drivers. PMID- 3337767 TI - The role of safety analysis in accident prevention. AB - The need for safety analysis has grown in the fields of nuclear industry, civil and military aviation and space technology where the potential for accidents with far-reaching consequences for employees, the public and the environment is most apparent. Later the use of safety analysis has spread widely to other industrial branches. General systems theory, accident theories and scientific management represent domains that have influenced the development of safety analysis. These relations are shortly presented and the common methods employed in safety analysis are described and structured according to the aim of the search and to the search strategy. A framework for the evaluation of the coverage of the search procedures employed in different methods of safety analysis is presented. The framework is then used in an heuristic and in an empiric evaluation of hazard and operability study (HAZOP), work safety analysis (WSA), action error analysis (AEA) and management oversight and risk tree (MORT). Finally, some recommendations on the use of safety analysis for preventing accidents are presented. PMID- 3337768 TI - An evaluation of the deterrent impact of Ontario's 12-hour licence suspension law. AB - The deterrent impact of Ontario's 12-hour licence suspension law, a law intended to mete out swift punishment is evaluated. A process model of deterrence is included. Time series analyses of the monthly log odds of number of positive B.A.C. fatalities over the number of negative B.A.C. fatalities indicated a small, short-term effect. The intermediate measures of four surveys of media coverage, Toronto residents, Ontario residents, and police forces supported these results, and affirmed the potential validity of the process model of deterrence. The results suggest that laws to increase the celerity and certainty of punishment will have little deterrent impact without enforcement and publicity of the new laws. PMID- 3337769 TI - Correlation between high-resolution computed tomography and surgical findings in congenital aural atresia. AB - Congenital aural atresia poses a great challenge, even to a competent otologic surgeon, due to innumerable types of malformations affecting the conduction and perception of sound. Roentgenographic evaluation by plain roentgenography is inconclusive in most cases; polytomography is helping to some extent. Recent generations of high-resolution computed tomographic (CT) scanners are probably the best. Seven cases of unilateral and three cases of bilateral congenital aural atresia were evaluated with high-resolution CT. Subsequently, ten ears were operated on. Surgical findings were correlated with CT scan findings with respect to atresia plate, extent of pneumatization, ossicular anomalies, bony facial nerve canal, and inner ear. Use of CT scans bears considerable importance in the management of these types of cases. High-resolution CT scan, when targeted for maximal bony detail, is possibly the method of choice in congenital aural atresia when surgical correction is contemplated. PMID- 3337771 TI - Audible and annoying spontaneous otoacoustic emissions. A case study. AB - Four types of evidence indicate that spontaneous otoacoustic emissions (SOAEs) might be the basis of one patient's problematic tinnitus. First, when SOAEs were suppressed, the tinnitus was inaudible. Second, pitch matches to the lowest pitch of the tinnitus corresponded to the lowest frequency of the SOAE. Third, there was a more intense multicomponent SOAE in the right than in the left ear, and patient claimed that the tinnitus was louder in the right ear. Fourth, the patient's SOAEs were unstable and for this reason they might be audible. One practical consequences of this research is that patients with pathological tinnitus (which keeps them awake at night and interferes with concentration) should be tested for SOAEs. Because SOAEs are abolished by aspirin, it is possible that some unusual cases of problematic tinnitus could be easily treated. PMID- 3337770 TI - Racial and familial factors in otitis media. A point prevalence study on Easter Island. AB - Of the 249 children aged 5 to 9 years who live on Easter Island, 220 underwent complete otolaryngological evaluation. Twenty children were found to have otitis media (acute, chronic, or both). Three of these children were genetically impure natives, nine were of mixed parentage, and eight were "continentals" (with a birth origin other than the island). None of the genetically pure natives had otitis media. Our data show that, in a population with all factors in common except for familial and racial background, the point prevalence of otitis media is higher in children of mixed or continental origin than in genetically pure native children. The high prevalence of otitis media in children of mixed parentage and in one particular family of European ancestry suggests the presence of intrinsic or pronicity factors that are seemingly transmissible. PMID- 3337772 TI - Early detection of hearing loss in children with cleft palates by brain-stem auditory response. AB - The hearing of 23 children with cleft palates was studied at an early age (before 12 months) and before pharyngoplasty using the electrophysiologic method of auditory brain-stem response. Nineteen children showed important degrees of conduction deafness of 50 or 60 dB. Results were compared with those obtained for a group of normal children tested under the same method before age 6 months. No hearing loss was observed in this group. It is concluded that hearing defects appear at an early age in children with cleft palates and are in direct relationship to the malformation. Hypotheses concerning the etiopathogeny of these hearing losses are proposed. PMID- 3337773 TI - Effects of cisplatin plus fluorouracil vs cisplatin plus cytarabine on head and neck squamous multicellular tumor spheroids. AB - We compared the efficacy of cisplatin plus fluorouracil vs cisplatin plus cytarabine against HEp-2 head and neck carcinoma cells in monolayer and multicellular tumor spheroid (MTS) systems. Increases in exposure time to cisplatin and fluorouracil from one to 24 hours resulted in approximately tenfold and 1000-fold increases, respectively, in cell lethality for both monolayer and MTS cells. Dose-response curves for cisplatin or fluorouracil on MTS cells closely followed those from monolayer cells, indicating good drug penetration into the MTS core. In contrast, dose-response curves on MTS cells after 24-hour exposure to cisplatin and cytarabine showed progressively lesser efficacy at higher drug concentrations. For monolayer cells, cisplatin plus fluorouracil and cisplatin plus cytarabine were both synergistic, the latter combination more synergistic than the former. For MTS cells, both combinations again showed synergistic interaction at moderate to high effect levels. Heightened synergistic interaction was demonstrated especially with the cisplatin plus cytarabine combination. Thus, the cisplatin plus cytarabine combination was always more synergistic than cisplatin plus fluorouracil. These data may serve as a basis for additional clinical trials of cisplatin plus cytarabine in the treatment of patients with head and neck carcinoma. PMID- 3337774 TI - The effect of cisplatin and fluorouracil on xenografted human squamous cell carcinoma of the head and neck. AB - In combined modality treatment, cisplatin and fluorouracil are considered to act synergistically. The assumption is based on results in murine leukemias and has not hitherto been tested on human squamous cell carcinoma. In the present study, cisplatin and fluorouracil, used singly and in combination, were tested on two human squamous cell carcinomas of the head and neck, xenografted to nude mice. Cisplatin (7.5 mg/kg) was given as a single-dose intraperitoneal injection and fluorouracil as repeated intraperitoneal injections every eight hours for four days to a total dose of 200 mg/kg. The toxicity of the cisplatin and fluorouracil combination was lower (27%) than that of fluorouracil alone (50%). Both drugs gave a dose-dependent inhibition of tumor volume growth. Using gained growth delay as endpoint, cisplatin and fluorouracil therapy exhibited a synergistic effect on both tumor lines. PMID- 3337775 TI - Temporary postthyroidectomy hypocalcemia. AB - The causes of temporary hypocalcemia after thyroidectomy are not well understood. In 18 patients undergoing unilateral (UL) and bilateral thyroid lobectomy (BL), an attempt was made to preserve all parathyroid glands with an intact blood supply. Total calcium (bound and free), free calcium (physiologically active form), albumin, parathyroid hormone, and calcitonin levels were serially measured. After UL, free calcium, parathyroid hormone, and calcitonin levels were unchanged, but total calcium level decreased because albumin level decreased. After BL, total calcium level decreased due to a decrease in albumin-bound calcium level. Free calcium level also decreased due to a decrease in parathyroid hormone level. Calcitonin level did not change. Despite careful preservation of the parathyroids and their blood supply, BL is frequently associated with temporary hypoparathyroidism. Techniques for preservation of parathyroid glands with their vascular integrity, correlation of surgical manipulation of parathyroids and calcium level, and calcium binding are discussed. PMID- 3337776 TI - The marginal mandibular nerve in rhytidectomy and liposuction surgery. AB - A concern in the current trend toward more aggressive undermining in rhytidectomy and liposuction surgery has been the potential for damage to the marginal mandibular nerve. This study was undertaken in an attempt to clarify the exact peripheral pathway of the marginal mandibular nerve. A series of 22 fresh cadaver heads were studied bilaterally by gross dissection and histologic studies. It was found that dissection superficial to the platysma up to a point 2 cm lateral to the lower lip can be done safely. Medial to this point, dissection is hazardous and is not indicated because the marginal mandibular nerve becomes more superficial as it travels to innervate its effector muscles. Additionally, dissection in this area is technically difficult because of the tight adherence of the skin to the underlying muscles. This adherence generally permits only the formation of fine superficial rhytids that are best treated by chemical peel or dermabrasion. PMID- 3337778 TI - Cicatricial velopharyngeal stenosis. AB - Cicatricial velopharyngeal stenosis is a complication of uvulopalatopharyngoplasty. Uvulopalatopharyngoplasty, posterior nasal packing, and instrumentation produced swelling and ulceration of the oropharyngeal mucosa. Prolonged intubation compounded the problem by pushing the freshly cut surface of the velum against a raw oropharyngeal wall, thus causing synechiae and, ultimately, stenosis. A surgical technique using a pharyngeal rotation flap and a free graft is proposed to treat this condition. PMID- 3337777 TI - Pigmentation, anesthesia, behavioral factors, and salicylate uptake. AB - In four experiments, 54 pigmented rats were used to examine the time course of sodium salicylate uptake in serum, cerebrospinal fluid, and perilymph. Subjects were tested under sodium pentobarbital anesthesia or while conscious. Compared with previously reported data from albino rats, pigmented subjects generally showed increased salicylate uptake. Moreover, the data suggested two different, time-dependent clearance mechanisms in conscious animals not observed in anesthetized rats. Daily injections of salicylate did not produce an accumulation of salicylate in serum. Systematically higher levels of salicylate were observed in perilymph compared with cerebrospinal fluid. Behavioral procedures, including water deprivation and conditioned suppression of ongoing drinking levels, had no effect on salicylate levels. PMID- 3337779 TI - Fungal mastoiditis in the immunocompromised host. AB - An immunocompromised patient is subject to unusual, severe opportunistic infections. We report a case of Aspergillus fumigatus mastoiditis in a patient with leukemia who also had cryptococcal meningitis. A fatal outcome ensued, despite extensive surgical and antimicrobial intervention. PMID- 3337780 TI - The use of magnetic resonance and computed tomography in the management of a patient with intrasinus hemorrhage. AB - The judicious use of computed tomography and magnetic resonance imaging in a critically ill patient with leukemia is discussed to demonstrate how a rapid and accurate diagnosis of intrasinus hemorrhage was established, thereby avoiding an unnecessary invasive procedure in this high-risk patient. In this clinical setting, a brief T1-weighted study distinguished between blood and infection. PMID- 3337781 TI - Congenital multiple fibromatosis (infantile myofibromatosis). AB - A female newborn had a rare case of congenital multiple fibromatosis, consisting of multiple fibrous lesions that histologically resemble myofibromas. Bony and soft-tissue lesions usually undergo spontaneous resolution, but excision may be required if vital structures are compromised as was the case in this patient. When the lesions involve the viscera in a generalized form of the disease, the result is often fatal. PMID- 3337782 TI - Pathologic quiz case 2. Plunging ranula (cervical ranula, cervical mucocele). PMID- 3337783 TI - Assessment of a new nasopharyngeal airway. AB - A new design of nasopharyngeal airway, which incorporates an introducer, was compared with a standard red rubber airway. The new airway was more frequently of the correct length, but the incidence of bleeding (12.5%) was not significantly different from that with the red rubber airway (27.5%). PMID- 3337784 TI - Re-expansion pulmonary oedema: slow decompression? PMID- 3337785 TI - Continuous pump infusions for extradural analgesia during labour. PMID- 3337786 TI - Extradural test doses in labour. PMID- 3337787 TI - Blood transfusions and colorectal cancer. PMID- 3337788 TI - Combined spinal-extradural anaesthesia for prostatectomy. PMID- 3337789 TI - Pregnancy delays paracetamol absorption and gastric emptying in patients undergoing surgery. AB - Gastric emptying may be delayed during pregnancy by hormonally mediated relaxation of the musculature of the stomach and by mechanical effects. In the present study, the rate of paracetamol absorption was used to measure gastric emptying in 14 non-pregnant women undergoing minor gynaecological surgery, and in 28 women undergoing termination of pregnancy. Of the pregnant patients 16 were of 8-11 weeks gestation and 12 were 12-14 weeks gestation. Paracetamol absorption was delayed in those who were 12-14 weeks pregnant compared with non-pregnant controls. Paracetamol absorption in the 8-11 weeks pregnant group was between the other two groups, but was not significantly different from either. PMID- 3337790 TI - Malignant hyperpyrexia and sudden infant death syndrome. AB - This paper reports three investigations of the suggested relationship between sudden infant death syndrome (SIDS) and malignant hyperpyrexia (MH). In the first study 151 MH-susceptible families completed a questionnaire designed to identify the incidence of SIDS within their own pedigree. In the second study 106 SIDS families completed a questionnaire designed to identify the incidence of anaesthetic related problems. In the third study, 14 SIDS parents were subjected to muscle biopsy and in vitro halothane contracture and caffeine contracture screening for susceptibility to MH. From the results of the three studies it can be concluded that there is no association between SIDS and MH. PMID- 3337791 TI - Post-tetanic count and profound neuromuscular blockade with atracurium infusion in paediatric patients. AB - In 38 paediatric surgical patients given atracurium by infusion, the degree of neuromuscular blockade was monitored using the post-tetanic twitch response. This was assessed by counting the number of visible responses when single twitch stimulation was applied at 1 Hz for 30 s after a 5-s tetanic stimulation at 50 Hz. A post-tetanic count of less than 10 correlated with a single twitch height of less than 5% of control, and ensured adequate paralysis. Once the count was greater than 15, the blockade could be antagonized readily. PMID- 3337792 TI - Comparison of recovery after neuromuscular blockade by atracurium or pancuronium. AB - Thirty patients were randomly allocated to receive either atracurium or pancuronium for neuromuscular blockade during surgery. At the end of the operation residual paralysis was antagonized with neostigmine. Voluntary strength was assessed at intervals after the antagonism, by observing grip strength, maximum inspiratory and expiratory force, 5-s head lift and the presence or absence of double vision. Grip strength and maximum expiratory force recovered significantly more quickly in the atracurium group over the 2-h measurement period. Double vision was significantly more frequent at up to 1 h when pancuronium had been used. At no time was there any significant difference between the two groups in respect of the 5-s head lift or, after 30 min, in the measurement of inspiratory force. PMID- 3337793 TI - Outcome after general anaesthesia for repair of fractured neck of femur. A randomized trial of spontaneous v. controlled ventilation. AB - One hundred and fifty-two patients undergoing surgery for fractured neck of femur were randomly allocated to receive either general anesthesia with spontaneous ventilation with nitrous oxide and halothane in oxygen or general anaesthesia with controlled ventilation with fentanyl, nitrous oxide and halothane in oxygen. Atracurium was used to provide muscle paralysis in 65% of the latter group, the remainder receiving no neuromuscular blocking agent other than suxamethonium for intubation. Patients were followed up for 6 months. Mortality and outcome were not significantly different between the groups. Overall mortality at 4 weeks was 5.2%, and at 6 months was 15.1%--figures which are considerably lower than in some other comparable studies. This study does not support the suggestion that general anaesthesia with controlled ventilation is associated with increased postoperative mortality. PMID- 3337794 TI - Double-blind, multiple-dose comparison of buprenorphine and morphine in postoperative pain of children. AB - In a randomized double-blind study of 57 children (aged 6 months-6 yr), pain following lateral thoracotomy was relieved with repeated i.v. doses of morphine 100 or 50 micrograms kg-1, or buprenorphine 3.0 or 1.5 micrograms kg-1. The same drug and dosage were continued and cardioventilatory indices, pain intensity and sedation measured for an observation period of 24 h. The sums of the pain intensity differences were equal in all groups. The mean doses for the complete initial analgesia were 230 and 180 micrograms kg-1 with the larger and the smaller bolus doses of morphine and 5.8 and 3.7 micrograms kg-1 with buprenorphine, respectively. The mean duration of action of buprenorphine was slightly but not significantly longer than that of morphine. The total consumption of both morphine and buprenorphine was less when the smaller bolus doses were used. Two patients developed a degree of ventilatory depression following repeated doses of buprenorphine. Buprenorphine was equal to morphine as a postoperative analgesic. PMID- 3337795 TI - Comparison of the effects of subanaesthetic concentrations of isoflurane or nitrous oxide in volunteers. AB - A cross-over trial was performed in 12 volunteers to compare the relative potency of 25% nitrous oxide and 0.4% isoflurane when breathed for a period of 20 min. Oxygen was used as a control. The effects were observed for 35 min after drug administration. Choice reaction time, ability to tap two areas on a board and ability to perform mathematical problems were significantly impaired when inhaling nitrous oxide, the maximum effect being obtained within 5 min. With isoflurane, the effects were significantly greater than with nitrous oxide. The effect obtained after 15 min inhalation was greater than that at 5 min. Tests returned promptly to the base line after the discontinuation of the test agent. Subjective assessments were made using a series of eight visual analogue scales. Results of the scales represented by physical and mental sedation indicated that 0.4% isoflurane was more potent than 25% nitrous oxide. Significant effects were detected up to 15 min after the inhalation of the agent was stopped. Subanaesthetic concentrations of isoflurane warrant further study in patients undergoing dental treatment in which a rapid recovery from sedation is important. PMID- 3337797 TI - The effect of phenylglyoxal on the translocation of pyruvate in rat-heart mitochondria. AB - The effect of phenylglyoxal, an arginine-specific reagent, on the translocation of pyruvate and on the binding of alpha-cyanocinnamate by rat-heart mitochondria has been studied. It has been found that both the uptake and the oxidation of pyruvate by mitochondria are inhibited by phenylglyoxal. The inhibitory potency increases with the increasing of the pH of the medium. Phenylglyoxal does not affect the transmembrane delta pH. Phenylglyoxal also inhibits the binding of alpha-cyanocinnamate to mitochondria. Substrates of the carrier, such as pyruvate itself and monochloroacetate, partially prevent the inhibition of alpha cyanocinnamate binding by phenylglyoxal, whilst acetate has no effect in this respect. Phenylglyoxal affects only the affinity of the alpha-cyanocinnamate binding site(s), without changing their total number. The results obtained indicate that arginine residues are involved in the mechanism of pyruvate translocation and of alpha-cyanocinnamate binding in rat-heart mitochondria. PMID- 3337796 TI - Comparative in vivo and in vitro assessment of the percutaneous absorption of local anaesthetics. AB - The percutaneous absorption of local anaesthetics in a standard formulation has been compared in vitro and in vivo. In vitro data were obtained with a modified Sartorius absorption system and silastic as a lipophilic barrier membrane. With this system the greatest steady-state flux values and permeability coefficients were obtained with amethocaine and lignocaine. These drugs also performed best in an in vivo volunteer trial. However, statistical analysis revealed that amethocaine was significantly better at producing full-depth anaesthesia to the challenge of insertion of a sterile needle. An optimized amethocaine formulation may therefore be expected to meet most closely the ideal profile for a percutaneous local anaesthetic preparation. PMID- 3337798 TI - Redistribution of the flux-control coefficients in mitochondrial oxidative phosphorylations in the course of brain edema. AB - This work describes the control exerted by dicarboxylate carrier and succinate dehydrogenase activities on the oxidative phosphorylations in rabbit brain mitochondria as an edema develops. Vasogenic edema leads to an uncompetitive inhibition of succinate dehydrogenase activity and to a large decrease of oxidative phosphorylations linked to succinate utilisation. Naftidrofuryl treatment in vivo restores both a high succinate dehydrogenase activity and a normal respiratory rate. In order to quantify the control of oxidative phosphorylations by the succinate dehydrogenase step, we applied the control analysis (Kacser, H. and Burns, J.A. (1973) in Rate Control of Biological Processes (Davies, D.D., ed.), pp. 65-104, Cambridge University Press, London; Heinrich, R. and Rapoport, T.A. (1974) Eur. J. Biochem. 42, 89-95). By using two inhibitors, one (phenylsuccinate) acting only on the dicarboxylate carrier and another (malonate) acting on both the dicarboxylate carrier and the succinate dehydrogenase, a method was developed to calculate the control coefficients of these two steps. The main result is that in mitochondria isolated from normal tissue succinate dehydrogenase exerted no control, but in the course of edema this enzymatic step became a controlling one: a transition from zero to a high control coefficient (0.5) was observed from the onset of intracellular edema for the threshold value of water/dry-weight tissue of 4.6. PMID- 3337799 TI - The quaternary structure of the plasma membrane b-type cytochrome of human granulocytes. AB - Hydrodynamic, crosslinking and immunoprecipitation studies were performed on detergent solubilized cytochrome b to demonstrate that the two copurifying polypeptides of molecular weight 91,000 (glycosylated) and 22,000 [1,2] formed a molecular complex. The hydrodynamic studies indicated that the cytochrome b/detergent complex had a sedimentation coefficient, partial specific volume and Stokes radius of 5.25 S, 0.82 cm3/g and 6.2 nm in Triton X-100 and 6.05 S, 0.80 cm3/g and 5.6 nm in octylglucoside, respectively. These studies also indicated that the detergent-protein complex has a molecular mass of 202 and 188 kDa in Triton X-100 and octylglucoside, respectively, is asymmetric in shape with a frictional coefficient of 1.3-1.4 and binds significant amounts of detergent. The molecular mass of the protein portion of the detergent-cytochrome complex was estimated to be between 100 and 127 kDa. Crosslinking studies with disuccinimidyl suberate and alkaline cleavable bis[2-(succinimidooxy-carbonyloxy)ethyl]sulfone revealed that the Mr = 91,000 and Mr = 22,000 components of purified cytochrome b are closely associated and can be covalently bound to form a polypeptide which, by SDS-polyacrylamide gel electrophoresis, has Mr values of 110,000-120,000 and 120,000-135,000 on 8% and 11% (w/v) SDS-polyacrylamide gels, respectively. Cleavage of the crosslinked species resulted in the reappearance of the Mr = 91,000 and Mr = 22,000 species. Sedimentation profiles of crosslinked cytochrome b in linear sucrose density gradients made up in H2O were identical to those of non-crosslinked controls. A close association of the two protein species was further confirmed by the ability of antibody specific for the smaller subunit to immunoprecipitate the larger one also. Experiments aimed at identifying the heme carrying subunit(s) were inconclusive, since dissociation of the complex resulted in loss of cytochrome b spectrum. These results, in combination with our SDS polyacrylamide gel electrophoresis molecular-weight estimates, provide strong evidence for the cytochrome b being an alpha-beta-type heterodimer composed of a glycosylated Mr = 91,000 and non-glycosylated Mr = 22,000 polypeptide. PMID- 3337800 TI - Evaluation of electron-transfer flavoprotein and alpha-lipoamide dehydrogenase redox states by two-channel fluorimetry and its application to the investigation of beta-oxidation. AB - A new method permitting the simultaneous evaluation of the redox states of alpha lipoamide dehydrogenase and electron-transfer flavoprotein in intact rat liver mitochondria by two-channel fluorimetry is described. It is shown that correction for the partial overlap of emission spectra can readily be introduced after a calibration procedure is performed. This method was applied to the investigation into regulation of palmitoylcarnitine oxidation. It was found that in the presence of rotenone, malonate and a redox buffer for the mitochondrial NAD system, the beta-oxidation flux was sensitive to variations in redox state of respiratory chain electron carriers at low states of NAD reduction. Therefore, the concept of beta-oxidation control caused solely by the NAD redox state can no longer be sustained. PMID- 3337801 TI - Evidence for membrane lipid peroxidation during the in vivo aging of human erythrocytes. AB - This study has examined the occurrence of lipid peroxidation in in vivo aged human erythrocyte membranes. Erythrocytes of various ages were separated on discontinuous stractan density gradients. Three erythrocyte fractions were analyzed: (I) Light--erythrocytes staying between stractan densities 1.053 and 1.043 g/ml, (II) predensest--erythrocytes staying between stractan densities 1.081 and 1.111, and (III) densest--erythrocytes passing stractan density 1.111. Peroxidative lipid damage of erythrocytes was assessed by measuring lipid extract fluorescence, by lipid thin-layer chromatography for the presence of adduct of phosphatidylserine (PS), phosphatidylethanolamine (PE) and malondialdehyde, and by thiobarbituric acid-reactivity. Fractions I, II and III contained, respectively, 0.2 +/- 0.1 (S.E.), 1.1 +/- 0.1 and 1.5 +/- 0.1 of phospholipid malondialdehyde adduct (percent of total phospholipids), and relative lipid fluorescence 22.5 +/- 0.8, 29.3 +/- 0.5, and 33.4 +/- 0.8 per ml packed cells, respectively. Thiobarbituric acid-reactivity of erythrocytes in various fractions was similar. Untreated densest erythrocytes contained significantly reduced PS (12.9 +/- 0.5%), in contrast to light erythrocytes (16.1 +/- 0.1%) and increased PC (31.2 +/- 0.3 versus 27.8 +/- 0.8% of the total phospholipid). This study provides evidence for significant lipid peroxidative damage in the erythrocyte membrane during aging in vivo. PMID- 3337802 TI - The role of membrane protein sulfhydryl groups in hydrogen peroxide-mediated membrane damage in human erythrocytes. AB - The formation of spectrin-hemoglobin complex following treatment of red cells with hydrogen peroxide (H2O2) has previously been shown to be associated with alterations in cell shape, decreased membrane deformability and increased recognition of modified cells by anti-IgM immunoglobulin in a phagocytic assay by monocytes. Prior treatment with carbon monoxide completely inhibited the H2O2 associated membrane changes, indicating a role for oxidized hemoglobin in the complex formation. Also, in a cell-free system, blockage of sulfhydryl (SH) groups on purified spectrin by N-ethylmaleimide significantly reduced the complex formation, suggesting a role for SH groups of spectrin in crosslinking process. The present study was undertaken to examine the role of SH blockade by N ethylmaleimide on intact red cells undergoing oxidative damage. Pretreatment of erythrocytes with N-ethylmaleimide at concentrations ranging from 0.1 to 0.2 mM resulted in decreased lipid peroxidation and spectrin hemoglobin crosslinking. Moreover, pretreatment with N-ethylmaleimide resulted in less marked alterations in cell shape and membrane deformability as well as reduced recognition of peroxidized cells by antiglobulin serum. N-Ethylmaleimide treatment had no effect on methemoglobin formation. Studies with 14C-labeled N-ethylmaleimide showed that over 50% of N-ethylmaleimide was incorporated into spectrin. Pretreatment of cells with higher concentrations of N-ethylmaleimide (over 0.2 mM) was associated with membrane dysfunction independent of H2O2. These results imply that blocking of reactive SH groups leads to reduced interaction of spectrin with oxidized globin. These data, along with our prior observations, indicate that SH groups on spectrin play an important role in hemoglobin oxidation-induced formation of spectrin-hemoglobin complex and the resultant deleterious effects on membrane properties. PMID- 3337803 TI - Interaction of erythrocyte protein 4.1 with phospholipids. A monolayer and liposome study. AB - We have studied the interaction of purified human erythrocyte protein 4.1 with phospholipid membranes by monitoring both the increase in surface pressure of monolayers at the air/water interface and the change in permeability in liposomes to fluorescent molecules, in the presence of protein 4.1. Protein 4.1 penetrated into monolayers of brain phosphatidylserine (PS) and egg phosphatidylcholine (PC), even above surface pressures of 30 mN/m. Protein 4.1 increased the permeability of negatively charged PS, but not PC, liposomes, measured as the increase in fluorescence when encapsulated 1-aminonaphthalene-3,6,8-trisulfonic acid (ANTS) and p-xylenebispyridinium bromide (DPX) or carboxyfluorescein were released into the medium. The interaction of protein 4.1 with PS large unilamellar vesicles (LUV) was increased as the pH and the ionic strength were lowered, and decreased as the Ca2+ or Mg2+ concentrations and ionic strength were raised. In order to study the relevance of these measurements to the erythrocyte, we prepared LUV of synthetic lipid mixtures characteristic of both the inner and the outer membrane leaflets. Protein 4.1 increased the permeability of inner, but not outer, leaflet LUV at both pH 6.0 and 7.4. These observations suggest that negatively charged phospholipid domains around the protein 4.1 high-affinity protein-binding site(s) may contribute to the anchoring of protein 4.1 to the cytoplasmic surface of the red cell membrane. PMID- 3337804 TI - Studies on sickled erythrocytes provide evidence that the asymmetric distribution of phosphatidylserine in the red cell membrane is maintained by both ATP dependent translocation and interaction with membrane skeletal proteins. AB - In order to study factors which are involved in maintenance of phosphatidylserine (PS) asymmetry within the human red cell membrane, we measured the effect of ATP depletion and of membrane skeleton/lipid bilayer uncoupling induced by sickling on the distribution of PS within the membrane bilayer of sickle cells. Trace amounts of radiolabeled PS were introduced into the outer membrane leaflet of both fresh and ATP-depleted reversibly sickled cells (RSCs), using a non-specific lipid transfer protein purified from bovine liver. The equilibration of the newly introduced PS over the two halves of the bilayer was monitored by treatment of the cells with phospholipase A2 which selectively hydrolyzes only those molecules present in the outer membrane leaflet. Within 1 h after insertion into fresh RSCs, only 10% of the labeled PS was accessible to the action of phospholipase A2. This fraction was markedly increased when the cells were subsequently deoxygenated. Prolonged deoxygenation of RSCs, deprived of their ATP after incorporation of radiolabeled PS, caused enhanced phospholipase A2-induced hydrolysis of radiolabeled PS. Similarly, phospholipase A2-induced hydrolysis of endogenous PS in intact RSCs was markedly enhanced when ATP-depleted, but not when fresh cells, were incubated under nitrogen for 3.5 h. Deoxygenated ATP depleted RSCs markedly enhanced the rate of thrombin formation in the presence of purified coagulation factors Xa, Va, prothrombin and Ca2+. This enhancement appeared to be dependent on the duration of incubation under nitrogen. This phenomenon, indicating the presence of increasing amounts of endogenous PS in the outer membrane leaflet, was not observed when either fresh RSCs or ATP-depleted normal erythrocytes were incubated under nitrogen. Our present observations provide evidence that, in addition to the interaction of PS with the skeletal proteins, an ATP-dependent translocation of PS is required to maintain its absolute asymmetric distribution in the human erythrocyte membrane. PMID- 3337805 TI - A study on the intracellular transport of prothrombin, albumin and transferrin in rat. AB - The intracellular transport of prothrombin in rat has been studied and compared with the transport of albumin and transferrin. The proteins were immunoisolated from plasma samples after pulse labelling with [3H]leucine and the secretion kinetics were determined. The half-times for secretion (t1/2) were approx. 30, 53 and 75 min for albumin, prothrombin and transferrin, respectively, whereas the minimal transit time for prothrombin was approx. 30 min, and those for albumin and transferrin 15-20 min. After injection of vitamin K-1 into warfarin-treated rats, the accumulated prothrombin precursor was gamma-carboxylated and secreted with a t1/2 of 37 min. This indicates that the gamma-carboxylation of prothrombin in rough endoplasmic reticulum cannot account for the delay in the transport of prothrombin as compared to albumin. Comparison of the incorporation of [3H]leucine and [3H]glucosamine into plasma prothrombin and transferrin suggested that transferrin is secreted randomly from an intracellular pool, whereas prothrombin is transported in a more orderly sequence. Moreover, treatment of rough microsomes with 0.05% sodium deoxycholate indicated that prothrombin is more tightly associated with the membranes of rough endoplasmic reticulum than albumin and transferrin. PMID- 3337806 TI - Modification of TSH-stimulated adenylate cyclase activity of bovine thyroid by manipulation of membrane phospholipid composition with a nonspecific lipid transfer protein. AB - The lipid composition of bovine thyroid plasma membranes was modified using the nonspecific lipid transfer protein from bovine liver. Incubation of plasma membranes with transfer protein and phosphatidylinositol-containing liposomes caused a strong, concentration dependent, inhibition of TSH-stimulated adenylate cyclase activity. Other phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidic acid were two to four times less effective as inhibitors of TSH-stimulation. The phosphatidylinositol-induced inhibition was not reversed when more than 80% of phosphatidylinositol incorporated was removed using phosphatidylinositol-specific phospholipase C. Incorporation of phosphatidylinositol in plasma membranes provoked no significant change in the fluorescence anisotropies of the fluorophores 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(14 trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), indicating that the inhibition was not due to changes in membrane fluidity. At phosphatidylinositol concentrations causing a 66% reduction in TSH-stimulated adenylate cyclase activity cholera toxin- and forskolin-stimulated activity as well as basal activity were decreased by maximally 10%. Since TSH binding to bovine thyroid plasma membranes was not affected it is suggested that phosphatidylinositol can act as a negative modulator of the TSH activation of adenylate cyclase and this probably by interfering with the coupling between the occupied TSH receptor and the stimulatory GTP-binding regulatory protein of the adenylate cyclase complex. PMID- 3337807 TI - Properties of odour-binding glycoproteins from rat olfactory epithelium. AB - The specific membrane glycoproteins with high affinity for camphor and decanal were isolated from rat olfactory epithelium. Antibodies to these glycoproteins inhibited both the electroolfactogram and the binding of odorants. The enzyme immunoassay has shown these glycoproteins to be present in the olfactory epithelium of rat, mouse, guinea-pig and hamster but not in that of frog and carp. The molecular mass of the odour-binding glycoproteins from rat olfactory epithelium solubilized by Triton X-100 was approx. 140 kDa. They consisted of two subunits (88 and 55 kDa). The 88 kDa subunit was capable of binding odorants. The data obtained suggest that the glycoproteins isolated have some properties that make them plausible candidates for olfactory receptor molecules. PMID- 3337808 TI - Association of daunomycin to membrane domains studied by fluorescence resonance energy transfer. AB - 1,6-Diphenyl-1,3,5-hexatriene and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5 hexatriene are fluorophores used to explore different hydrophobic domains of membrane bilayers (Andrich, M.P. and Vanderkooi, J.M. (1976) Biochemistry 15, 1257-1265; Prendergast, F.G., Haugland, R.P. and Callahan, P.J. (1981) Biochemistry 20, 7333-7338). Fluorescence resonance energy transfer between these fluorophores, acting as energy donors, and the anthracycline, daunomycin, as the acceptor, was used to analyze the interaction of the drug with natural membranes, and its relative location within the membrane bilayer. The transfer process was demonstrated by: (1) emission fluorescence of the acceptor when the samples were excited at the excitation maximum of the donor (360 nm); and (2) progressive quenching of the energy donor (at 428 nm) when in the presence of increasing acceptor concentration. Also, the disruption of the energy transfer by solubilization of the membrane with Triton X-100 evidences a role for the membrane in providing the appropriate site(s) for energy transfer to occur. At moderately low daunomycin/membrane lipid ratios, the different efficiencies of resonance energy transfer between the two donors and daunomycin predicts a preferential, but not exclusive, location of the drug at membrane 'surface' domains, i.e., those regions of the bilayer explored by the 1-(4 trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene probe. In support of this observation, a large fraction (approx. 75%) of membrane-associated daunomycin was rapidly sequestered away from the membrane upon addition of excess DNA, which forms high-affinity complexes with daunomycin (Chaires, J.B., Dattagupta, n. and Crothers, D.M. (1982) Biochemistry 21, 3927-3932), thus acting as a drug 'sink'. Also, a large fraction of drug was accessible to fluorescence quenching by iodide, a collisional water-soluble quencher. On the other hand, a smaller population of the membrane-associated daunomycin was characterized by slow sequestering by the added DNA and inaccessibility to quenching by iodide. We conclude that the daunomycin, which is only slowly sequestered, is located deep within the hydrophobic domains of the bilayer, likely to be those probed by 1,6 diphenyl-1,3,5-hexatriene. PMID- 3337809 TI - Biphasic nature of the binding of cationic amphipaths with artificial and biological membranes. AB - We have studied the interaction with liposomes and red cell membrane of various cationic amphipaths, chlorpromazine, methochlorpromazine, imipramine and propranolol. At low concentrations the interaction is a partition of the molecule between the lipid hydrophobic phase and the aqueous medium. The extent of the partition is dependent on the membrane composition or physical properties, on the incubation conditions (pH, ions) and on the amphipath used. After a given amount of amphipath has entered in the membrane, a new type of interaction appears which leads to an apparent saturable association. This association, which probably involves the anionic groups of the membrane components, might result from structural or/and electrical membrane perturbations induced by the presence of drug molecules between the phospholipids. Thus the interaction of a molecule of cationic amphipath with a membrane varies according to the amount of drug present. PMID- 3337810 TI - The lateral distribution of cholesterol in the plane of lipid multibilayers. AB - We consider three models of cholesterol distribution in the plane of a bilayer of DMPC. We analyse recent 2H-NMR data obtained from deuterated fluorescent probes and show that, on the characteristic time-scale of 2H-NMR, it is in accord with a random distribution of cholesterol in a fluid-like DMPC bilayer in a single phase at least for T greater than or approximately equal to 35 degrees C and for 0 less than or equal to c less than or equal to 0.42. PMID- 3337811 TI - Evidence for the involvement of the transcortin carbohydrate moiety in the glycoprotein interaction with the plasma membrane of human placental syncytiotrophoblast. AB - We have studied the interaction of human transcortin and the pregnancy-associated transcortin variant with the microvesicular membrane fraction derived from the human placental syncytiotrophoblast. Two classes of specific binding sites for these glycoproteins were found in this membrane preparation. One of these displays a relatively high binding capacity, Bmax = 140 +/- 60 fmol transcortin per mg membrane protein, and a significantly higher affinity for transcortin, Kd = (1.6 +/- 0.6).10(-10) mol/l, than for the pregnancy-associated variant, Kd = (4.5 +/- 1.2).10(-9) mol/l. On the contrary, another class of the binding sites, occurring in the membranes at a far lower concentration: Bmax = 3.0 +/- 2.2 fmol transcortin per mg membrane protein, shows a higher affinity for the pregnancy associated transcortin variant, Kd = (3.3 +/- 2.0).10(-12) mol/l, than for normal transcortin, Kd = (2.5 +/- 0.7).10(-11) mol/l. Since the pregnancy-associated variant differs from normal transcortin with respect to its carbohydrate structures only (Avvakumov, G.V. and Strel'chyonok, O.A. (1987) Biochim. Biophys. Acta 925, 11-16), the results of the present work suggest that the transcortin carbohydrates are directly involved in the specific interaction of this serum hormone-binding globulin with the plasma membrane of the placental syncytiotrophoblast. PMID- 3337813 TI - Reduced levels of sialic acid in the plasma membrane during hepatocellular proliferation. AB - When rats were infused with a solution containing triiodothyronine, amino acids, glucagon and heparin (solution A) the hepatocytes increased DNA synthesis and decreased plasma membrane sialic acid. In order to study whether the reduced levels of sialic acid in the plasma membrane were associated with hepatocyte proliferation, different mixtures of three components of solution A were infused into rats and the DNA synthetic activity as well as the sialic acid content measured. Results reported here show a correlation between DNA synthetic activity and sialic acid reduction suggesting that the decrease in the plasma membrane sialic acid can be a pre-replicative step associated to cell proliferation. PMID- 3337812 TI - Analysis of glycosaminoglycans in bovine retinal microvessel basement membrane. AB - Glycosaminoglycans (GAG) were isolated from bovine retinal microvessel basement membrane (RMV-BM) and quantitatively analyzed using a recently described competitive binding assay that is specific for and sensitive to nanogram amounts of heparan and chondroitin sulfates. Treatment of osmotically lysed retinal microvessels with the ionic detergent deoxycholate (DOC), required for liberation of the extracellular matrix for plasma membrane lipoproteins and purification of the insoluble matrix, solubilized less than 5% of the GAG in the water-insoluble material. Total GAG content in the DOC-insoluble basement membranes was approx. 0.52 micrograms/mg dry weight; about 70% of the measurable GAG was resistant to both chondroitinase ABC and chondroitinase AC digestion and was sensitive to nitrous acid treatment, indicating its heparan sulfate nature. Cellulose acetate electrophoresis revealed two bands, one of which had an electrophoretic mobility similar to heparan sulfate standard and was sensitive to nitrous acid; the other migrated in the same position as chondroitin sulfate standard and was sensitive to chondroitinase ABC and chondroitinase AC digestion. These results provide evidence that RMV-BM contains chondroitin sulfate(s) as well as heparan sulfate, and offer the first quantitative analysis of GAG in this extracellular matrix. PMID- 3337814 TI - Spectroscopic and ionization properties of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) labeled lipids in model membranes. AB - The spectroscopic and ionization properties of various lipids labeled with the 7 nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group have been studied in model membranes using fluorescence, absorbance and electrophoretic mobility measurements. Electrophoretic measurements show that the NBD group is uncharged at neutral pH. However, at high pH, hydroxyl addition or deprotonation occurs with a pKa, depending upon conditions, of 11.5-11.8 for the NBD group of headgroup-labeled phosphatidylethanolamine (NBD-PE) and 11.1-11.5 for NBD labels placed at the end of one fatty acyl chain of a phosphatidylcholine (6-NBD-PC and 12-NBD-PC). This type of behavior is not observed in the case of a methylated NBD label placed in the flexible 'tail' of cholesterol (NBD-cholesterol). The similarity in pKa for NBD-PE and NBD-PCs suggests that in these cases the NBD group is at a similar depth in the membrane. This was examined further by comparison of the fluorescence emission maximum of the NBD group in model membranes with that in solvents of varying polarity. The apparent polarity experienced by NBD groups in model membranes indicates that for NBD-PE and 12-NBD-PC they are located at the polar region whereas the NBD group of NBD-cholesterol is deeply buried in a nonpolar region of the membrane. This conclusion is supported further by fluorescence quenching experiments measuring NBD exposure to the aqueous quencher Co2+. The results of this study confirm the tentative conclusions of our previous fluorescence quenching studies on the location of NBD groups in model membranes. PMID- 3337815 TI - Phospholipase A2 hydrolysis of membrane phospholipids causes structural alteration of the nicotinic acetylcholine receptor. AB - Thermal perturbation techniques have been used to probe structural alteration of the nicotinic acetylcholine receptor as a function of perturbations of its native membrane environment. Differential scanning calorimetry and a technique involving heat inactivation of the alpha-bungarotoxin-binding sites on the receptor protein reveal that there is a profound destabilization of the acetylcholine receptor structure when receptor-containing membranes are exposed to phospholipase A2. The characteristic calorimetric transition assigned to irreversible denaturation of the receptor protein and the heat inactivation profile of alpha-bungarotoxin binding sites are shifted to lower temperatures by approx. 7 and 5 C degrees, respectively, upon exposure to phospholipase A2 at a phospholipase/neurotoxin binding site molar ratio of about 1:100. The effects of phospholipase A2 on receptor structure can be (i) reversed by using bovine serum albumin as a scavenger of phospholipase hydrolysis products of membrane phospholipids, and (ii) stimulated by incorporation into the membranes of free, polyunsaturated fatty acids. In particular, linolenic acid (18:3(n-3] causes detectable destabilization of the alpha-bungarotoxin binding sites on the receptor at free fatty acid/receptor molar ratios as low as 10:1. Furthermore, alteration of receptor structure by added phospholipase occurs very rapidly, which is consistent with the observation of rapid in situ phospholipase A2 hydrolysis of membrane phospholipids, particularly highly unsaturated phosphatidylethanolamine and phosphatidylserine. Based on previously published data on the inhibition of acetylcholine receptor cation-gating activity caused by the presence of either phospholipase A2 or free fatty acids (Andreasen T.J. and McNamee M.G. (1980) Biochemistry 19, 4719), we interpret our data as indicative of a correlation between structural and functional alterations of the membrane-bound acetylcholine receptor induced by phospholipase A2 hydrolysis products. PMID- 3337816 TI - Hepatocellular uptake of cyclosporin A by simple diffusion. AB - Cyclosporin A is known to be eliminated mainly via the biliary++ pathway after biotransformation. Whether liver cells take up the drug by simple diffusion across the lipid barrier or by carrier-mediated transport, as shown for some other peptides, was unknown up to the present. Experiments with [3H]cyclosporin A on isolated rat hepatocytes indicate that the uptake of cyclosporin A is neither saturable nor is driven by metabolic energy. Cholestasis caused by cyclosporin A treatment is therefore not the result of mutual competition for a carrier protein. Nevertheless, cyclosporin A interacts with the bile acid transport system by non-competitive inhibition of bile salt uptake. PMID- 3337817 TI - Surface charge modulation of liposomes by enzymatic hydrolysis of macrocyclic 1,2 dotriacontanedioyl-sn-glycero-3-phosphocholine. AB - 1,2-Dotriacontanedioyl-sn-glycero-3-phosphocholine (dTPC) was synthesized, and by a sonication method, dTPC was transformed into liposomes with physical features (charge, size, gel-to-liquid crystalline phase transition constants, etc.) similar to those of liposomes made of acyclic 1,2-dipalmitoyl-sn-glycero-3 phosphocholine (DPPC). Quantitative enzymatic assays using phospholipases A2 and C showed that dTPC was comparable with or better than DPPC as a substrate. Remarkably, the liposomes assembled from a mixture of dTPC and 1,2-distearyl-sn glycero-3-phosphocholine were converted rapidly into anionic liposomes at pH 7 by the action of phospholipase A2, keeping their vesicular structure and exposing CO2H groups of the lysolipids of dTPC on the membrane surface. The use of dTPC is discussed in conjunction with the enzyme-catalyzed modification of the liposomes. PMID- 3337818 TI - Inhibition of calcium release from skeletal muscle sarcoplasmic reticulum by calmodulin. AB - The effect of calmodulin on calcium release from heavy sarcoplasmic reticulum isolated from rabbit skeletal muscle was investigated with actively and passively calcium loaded sarcoplasmic reticulum vesicles and measured either spectrophotometrically with arsenazo III or by Millipore filtration technique. The transient calcium-, caffeine- and AMP-induced calcium release from actively loaded sarcoplasmic reticulum vesicles was reduced to 29%, 51% and 59% of the respective control value by 1 microM exogenous calmodulin. Stopped-flow measurements demonstrate that calmodulin reduces the apparent rate of caffeine induced calcium release from actively loaded sarcoplasmic reticulum. The rate of calcium uptake measured in the presence of ruthenium red, which blocks the calcium release channel, was not affected by calmodulin or calmodulin-dependent phosphorylation of sarcoplasmic reticulum vesicles with ATP[S]. The rate of the calcium-, caffeine- and AMP-induced calcium release from passively loaded sarcoplasmic reticulum vesicles was reduced 1.4-2.0-fold by 1 microM exogenous calmodulin, i.e. the half-time of release was maximally increased by a factor of two, whilst calmodulin-dependent phosphorylation of a 57 kDa protein with ATP[S] had no effect. The data indicate that calmodulin itself regulates the calcium release channel of sarcoplasmic reticulum. PMID- 3337819 TI - Drug-induced calcium release from heavy sarcoplasmic reticulum of skeletal muscle. AB - Calcium release from isolated heavy sarcoplasmic reticulum of rabbit skeletal muscle by several calmodulin antagonistic drugs was measured spectrophotometrically with arsenazo III and compared with the properties of the caffeine-induced calcium release. Trifluoperazine and W7 (about 500 microM) released all actively accumulated calcium (half-maximum release at 129 microM and 98 microM, respectively) in the presence 0.5 mM MgCl2 and 1 mg/ml sarcoplasmic reticulum protein; calmidazolium (100 microM) and compound 48/80 (70 micrograms/ml) released maximally 30-40% calcium, whilst bepridil (100 microM) and felodipin (50 microM) with calmodulin antagonistic strength similar to trifluoperazine (determined by inhibition of the calcium, calmodulin-dependent protein kinase of cardiac sarcoplasmic reticulum) did not cause a detectable calcium release, indicating that this drug-induced calcium release is not due to the calmodulin antagonistic properties of the tested drugs. Calcium release of trifluoperazine, W7 and compound 48/80 and that of caffeine was inhibited by similar concentrations of magnesium (half-inhibition 1.4-4.2 mM compared with 0.97 mM for caffeine) and ruthenium red (half-inhibition for trifluoperazine, W7 and compound 48/80 was 0.22 microM, 0.08 microM and 0.63 micrograms/ml, respectively, compared with 0.13 microM for caffeine), suggesting that this drug induced calcium release occurs via the calcium-gated calcium channel of sarcoplasmic reticulum stimulated by caffeine or channels with similar properties. PMID- 3337820 TI - Interaction of 14C-labelled amphotericin B derivatives with human erythrocytes: relationship between binding and induced K+ leak. AB - Four 14C-labelled amphotericin B (Am B) derivatives with different net electric charges were examined: zwitterionic N-fructosyl Am B, positively charged N fructosyl Am B methyl ester, negatively charged N-acetyl Am B and neutral N acetyl Am B methyl ester. The binding of these four derivatives to human red cells and their octanol-water partition coefficients were measured. Simple partitioning between red cells and buffer was found for the four compounds, regardless of concentration, within a range of 10(-8) and 10(-4) M. This indicates the absence of cooperativity and saturability of binding at least in this concentration range. The constant partition coefficients were found to be three to five times higher for the two methyl ester derivatives than for the two non-esterified compounds. All partition coefficients were proportional to those found for the octanol-water system. Efficiency in inducing K+ leak from red cells was measured during the binding experiments. Despite the higher partition coefficients of the two methyl ester derivatives, they were found to have much lower ionophoric efficiency than the two non-esterified compounds. These results are discussed in terms of the mechanism of permeability pathway formation by polyene antibiotics. PMID- 3337821 TI - 1H-NMR heme resonance assignments by selective deuteration in low-spin complexes of ferric hemoglobin A. AB - The heme methyl and vinyl alpha-proton signals have been assigned in low-spin ferric cyanide and azide ligated derivatives of the intact tetramer of hemoglobin A, as well as the isolated chains, by reconstituting the proteins with selectively deuterated hemins. For the hemoglobin cyanide tetramer, assignment to individual subunits was effected by forming hybrid hemoglobins possessing isotope labeled hemins in only one type of subunit. The heme methyl contact shift pattern has 1-methyl and 5-methyl shifts furthest downfield in both chains and the individual subunits of the intact hemoglobin in both the cyanide- and azide ligated species, which is consistent with a dominant rhombic perturbation due to the proximal His-F8 imidazole pi bonding in the known structure for human adult hemoglobin. The individual chain and subunit assignments confirm that the detailed electronic/magnetic properties of the heme pocket are essentially unaltered upon assembling the R-state tetramer from the isolated subunits. PMID- 3337823 TI - Effect of limited tryptic modification of a bacterial poly(3-hydroxybutyrate) depolymerase on its catalytic activity. AB - The extracellular poly(3-hydroxybutyrate) depolymerase of Alcaligenes faecalis T1, which hydrolyzes both hydrophobic poly(3-hydroxybutyrate) and water-soluble oligomers of D(-)-3-hydroxybutyrate, lost its hydrolyzing activity toward the hydrophobic substrate on mile trypsin treatment, but retained its activity toward water-soluble oligomers. The molecular mass of the trypsin-treated enzyme was 44 kDa, as estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, which was 6 kDa smaller than that of the native enzyme (50 kDa). The trypsin-treated enzyme seemed to be less hydrophobic than the native one, because it was rather weakly adsorbed to a hydrophobic butyl-Toyopearl column compared with the native enzyme, and showed no ability to bind to poly(3 hydroxybutyrate), to which the native enzyme tightly bound. These results suggest that, in addition to a catalytic site, the enzyme has a hydrophobic site, which is not essential for the hydrolysis of water-soluble oligomers, but is necessary for the hydrolysis of hydrophobic substrates, and this hydrophobic site is removed from the enzyme by the action of trypsin. PMID- 3337822 TI - Mossbauer spectroscopic studies of deproteinised, sub-fractionated and reconstituted ferritins: the relationship between haemosiderin and ferritin. AB - In a previous study of human haemosiderin and ferritin by a combination of Mossbauer spectroscopy and electron microscopy, it was observed that the Mossbauer spectra of haemosiderin showed a very different temperature dependence to those of ferritin. These differences were related to the superparamagnetic behaviour of small particles of a magnetic material and suggested that the magnetic anisotropy constant of the haemosiderin was considerably larger than that of the ferritin. In the present work, samples of ferritin have been examined by Mossbauer spectroscopy following partial deproteinisation, subfractionation, and reconstitution with and without phosphate, in order to investigate whether these procedures lead to changes in the magnetic anisotropy constant of the iron containing cores. There is no evidence from the present data that changes in the protein shell, in the size of the iron-containing cores of ferritin, or in the phosphate content lead to any significant changes in the magnetic anisotropy constant, as obtained from the temperature dependence of the Mossbauer spectra. These results indicate that the different magnetic anisotropy constant observed in the case of human haemosiderin resulting from transfusional iron overload must arise from other significant differences in the composition or structure of the iron-containing cores. PMID- 3337824 TI - Binding of high-mobility-group proteins HMG 14 and HMG 17 to DNA and histone H1 as influenced by phosphorylation. AB - We have used affinity chromatography to study the effects of phosphorylation of calf thymus high-mobility-group proteins HMG 14 and HMG 17 on their binding properties towards calf thymus single- and double-stranded DNA and histone H1. Without in vitro phosphorylation, HMG 14 and HMG 17 eluted from double-stranded DNA-columns at 200 mM NaCl. HMG 14 was released from single-stranded DNA-column at 300 mM NaCl and from H1-column at 130 mM NaCl, whereas the corresponding values for HMG 17 were 230 mM and 20 mM, respectively. Phosphorylation of HMG 14 and HMG 17 by cAMP-dependent protein kinase (A-kinase) decreased markedly their affinity (270 mM and 200 mM NaCl, respectively) for single-stranded DNA, whereas HMG 14 phosphorylated by nuclear protein kinase II (NII-kinase) eluted only slightly (290 mM NaCl) ahead of the unphosphorylated protein. HMG 14 phosphorylated by both A-kinase and NII-kinase eluted from double-stranded DNA columns almost identically (190 mM NaCl) with the unphosphorylated protein. Interestingly, phosphorylation of HMG 14 by NII-kinase increased considerably its affinity for histone H1 and the phosphorylated protein eluted at 200 mM NaCl. Phosphorylation of HMG 14 by A-kinase did not alter its interaction towards histone H1. These results indicate that modification of HMG 14 by phosphorylation at specific sites may have profound effects on its binding properties towards DNA and histone H1, and that HMG 17 has much weaker affinity for single-stranded DNA and histone H1 than HMG 14. PMID- 3337825 TI - Mouse alpha chains inhibit polymerization of hemoglobin induced by human beta S or beta S Antilles chains. AB - A murine model of sickle cell disease was tested by studying the polymerization of hybrid hemoglobin tetramers between alpha mouse and human beta S or beta S Antilles chains were prepared from Hb S Antilles, which was a new sickling hemoglobin inducing a sickle cell syndrome more severe than Hb S. The hybrid molecules did not polymerize in solution, indicating that the mouse alpha chains inhibited fiber formation. Consequently, a mouse model for sickle cell disease requires the transfer and expression of both alpha and beta S or beta S Antilles genes. PMID- 3337826 TI - The secondary structure of a membrane-embedded peptide from the carboxy terminus of lipophilin as revealed by circular dichroism. AB - Several intramembranous peptides have been isolated from the major myelin proteolipid protein (lipophilin) isolated from normal human myelin membrane after labelling the protein with a membrane-permeable photolabel, 3-(trifluoromethyl)-3 (m-[125I]iodophenyl)diazirine. Peptide T-3, comprising residues 205-268, represents the C-terminal portion of the protein. Reconstitution of peptide T-3 into lipid vesicles prepared from egg phosphatidylcholine (PC) or into lysoPC micelles yielded visually transparent preparations, free of scattering artifacts, which were used for circular dichroism studies to assess the extent of secondary structure in the peptide. Peptide T-3 had a high degree of alpha-helix in various environments. In aqueous environment, the secondary structure was 45% alpha helix, 33% beta-structure and 9% beta-turns. Transfer of the peptide to PC vesicles or lysoPC micelles increased the proportion of alpha-helix and decreased that of beta-structure. In PC vesicles, the alpha-helical content was 80% with little or no beta-structure. Small amounts of other structures such as beta-turns and unordered structures were also present. The partitioning of this C-terminal section of lipophilin into membranes may have an important role initiating and/or stabilizing the native conformation of lipophilin in the myelin membrane. PMID- 3337827 TI - The solution structure of concanavalin A probed by FT-IR spectroscopy. AB - The secondary structural properties of various forms of concanavalin A in solution were investigated by Fourier-transform infrared spectroscopy in the Amide I region. As in the crystal, the solution structure of the native protein consists mainly of antiparallel beta-sheet. Carbohydrate binding does not produce major changes in the overall secondary structure of concanavalin A, but affects infrared bands due to loops and beta-turns. Upon demetallization, the spectrum of concanavalin A shows only a small change in the Amide I band, indicating that whereas the beta-sheet structure is conserved, the tertiary properties may be altered. There are also changes in the bands from the tyrosine residues which are compatible with local changes in structure. Confirming tertiary structural differences, the cation-depleted apoprotein is much less stable, denaturing around 63 degrees C, while the native protein denatures only at temperatures around 85 degrees C. Tetramerization proceeds without significant secondary structural change. However, aggregation of the tetramers leads to a significant decrease of the bands corresponding to beta-sheet structure, and changes in the tyrosine bands. PMID- 3337828 TI - Coenzyme A dithioesters: synthesis, characterization and reaction with citrate synthase and acetyl-CoA:choline O-acetyltransferase. AB - Acyl dithioesters of CoA have been synthesized by transesterification. The alpha hydrogens have a spectrally determined pKa of 12.5 +/- 0.14. The hydroxide catalyzed enolization rate is estimated to be 600 M-1.s-1. The absorbance of the dithioester, lambda max = 306 nm, can be used to monitor both the condensation and transesterification reactions that use CoA-Ac as a substrate. For citrate synthase at pH 7.4 Vmax = (4.0 +/- 0.4).10(-4) s-1 and Km = 53 +/- 7.5 microM, which are 2.10(-6) and 3.3-times the Vmax and Km values observed for CoAS-Ac, while for Ac-CoA: choline O-acetyltransferase (EC 2.3.1.6) at pH 7.0 Vmax = (1.1 +/- 0.2).10(-2) mumol.s-1.(mg protein)-1 and Km = 83 +/- 33 microM, which are 0.077 and 10-times the values observed with CoAS-Ac, respectively. The CoA dithioesters are stable at low pH, but hydrolyze with a second-order rate constant of 8.2.10(-2) M-1.s-1 at pH 11.4. The spectral properties of these dithioesters should allow these analogs to be used as probes of the structure of enzyme bound intermediates. PMID- 3337829 TI - Purification and characterization of NADP+-linked isocitrate dehydrogenase from an alkalophilic Bacillus. AB - We have succeeded in purifying to homogeneity a very labile NADP+-linked isocitrate dehydrogenase (isocitrate: NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42) from a strain of alkalophilic Bacillus, by a simple method, with an overall yield over 76% of the original activity. The molecular weight on Sephadex G-200 was around 90,000; and that by electrophoresis on SDS-polyacrylamide gels was about 44,000. The sedimentation coefficient (s020,w) and isoelectric point of the enzyme were determined to be 3.22 S and pH 4.7, respectively. The enzyme required Mn2+ for the reaction and for stability. The optimum pH for the reaction was in the range 7.8-8.4 at 30 degrees C; the optimum temperature at pH 8.0 was 75 degrees C; the activation energy of the reaction was 6.2 kcal/mol. The Km values for threo-Ds-isocitrate, DL-isocitrate, and NADP+ were 5.4 microM, 9.9 microM, and 7.3 microM, respectively. This enzyme was inhibited by NADPH, glyceraldehyde 3-phosphate, 3-phosphoglycerate, phosphoenol pyruvate, cis aconitate, alpha-ketoglutarate, and oxaloacetate. In addition, it was subject to a concerted inhibition by a combination of glyoxylate and oxaloacetate, and also to a cumulative inhibition by nucleoside triphosphates. PMID- 3337830 TI - Inactivation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase by koningic acid. AB - Koningic acid, a sesquiterpene antibiotic, is a specific inhibitor of the enzyme glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12). In the presence of 3 mM of NAD+, koningic acid irreversibly inactivated the enzyme in a time-dependent manner. The pseudo-first-order rate constant for inactivation (kapp) was dependent on koningic acid concentration in saturate manner, indicating koningic acid and enzyme formed a reversible complex prior to the formation of an inactive, irreversible complex; the inactivation rate (k 3) was 5.5.10(-2) s-1, with a dissociation constant for inactivation (Kinact) of 1.6 microM. The inhibition was competitive against glyceraldehyde 3-phosphate with a Ki of 1.1 microM, where the Km for glyceraldehyde 3-phosphate was 90 microM. Koningic acid inhibition was uncompetitive with respect to NAD+. The presence of NAD+ accelerated the inactivation. In its absence, the charcoal-treated NAD+-free enzyme showed a 220 fold decrease in apparent rate constant for inactivation, indicating that koningic acid sequentially binds to the enzyme next to NAD+. The enzyme, a tetramer, was inactivated when maximum two sulfhydryl groups, possibly cysteine residues at the active sites of the enzyme, were modified by the binding of koningic acid. These observations demonstrate that koningic acid is an active site-directed inhibitor which reacts predominantly with the NAD+-enzyme complex. PMID- 3337832 TI - Association of chlorphentermine with phospholipids in rat alveolar lavage materials, alveolar macrophages and type II cells. AB - Administration of chlorphentermine to rats leads to an increase in the phospholipid content of pulmonary surfactant materials and alveolar macrophages. It is known that this drug binds to pure phospholipids and prevents their degradation by phospholipases. Therefore, experiments were carried out to determine if chlorphentermine binds to surfactant phospholipids in vitro and to measure the in vivo association of drug with phospholipids in alveolar lavage materials from rats injected with [14C]chlorphentermine. The presence of chlorphentermine in alveolar macrophages, type II cells and other small pneumocytes (a population of lung cells which does not include alveolar macrophages or type II cells) from treated animals was also assessed. Binding of the drug to surfactant phospholipids, as measured with the fluorescent probe, 1 anilino-8-naphthalene sulfonate, occurs in vitro and does not differ in various subfractions of alveolar lavage materials isolated by differential centrifugation. Following daily administration of chlorphentermine to rats for 3 days, the drug appears to be associated with surfactant phospholipids such that the molar ratio is 1:100 (chlorphentermine/phospholipid). Chlorphentermine is also associated with alveolar macrophages (molar ratio, 1:18) and type II cells (molar ratio, 1:33). Not much drug is associated with the population of other lung cells (molar ratio, 1:333). In alveolar macrophages, approx. 70% of the drug seems to be bound to phospholipid and/or sequestered in subcellular organelles. However, only 20% of the chlorphentermine is bound and/or sequestered in type II cells. The results of these experiments suggest that following chlorphentermine administration, the drug is associated with phospholipids in acellular pulmonary lavage materials, alveolar macrophages and type II cells. This drug-phospholipid interaction may impair phospholipid degradation and lead to a phospholipidosis in surfactant materials and alveolar macrophages. PMID- 3337831 TI - Metabolism of 6,9,12-octadecatrienoic acid and 6,9,12,15-octadecatetraenoic acid by rat hepatocytes. AB - When 5.10(6) hepatocytes were incubated for 40 min with 0.015-0.3 mM (1-14C) labeled 6,9,12-octadecatrienoic acid or (1-14C)-labeled 6,9,12,15 octadecatetraenoic acid there was a concentration-dependent acylation of radioactive metabolites into both phospholipids and triacylglycerol. However, when the concentration of either substrate exceeded 60-150 microM there was no further increase in the metabolism of either substrate to longer-chain (n-6) and (n-3) acids. When cells were then incubated for various periods of time with 60 microM substrate there was initial rapid removal of the substrate which was accompanied by its acylation into lipids. Over time, the amount of both substrates in lipids declined without an overall drop in specific activity. This decline was accompanied by an increase in long-chain (n-6) and (n-3) fatty acids. Similar results were obtained when the time-dependent metabolism of the two substrates was examined in individual hepatocyte phospholipids. Collectively, these findings suggest that when these two 18-carbon acids are produced by desaturation of dietary linoleate and linolenate that they are in part initially acylated into a labile phospholipid pool. Rapid release and subsequent further metabolism to longer-chain (n-6) and (n-3) acids may explain why these products of the 6-desaturase do not accumulate in membrane lipids. PMID- 3337833 TI - Effect of phospholipids on fluorescence polarization and lifetimes of fluorescein labeled phospholipase A2. AB - Phospholipids and divalent metal ions induce changes in the fluorescence polarization of fluorescein-labeled phospholipase A2 from the Indian cobra (Hazlett, T.L. and Dennis, E.A. (1985) Biochemistry 24, 6152-6158) which may be indicative of enzyme aggregation. Lifetimes and rotational correlation times of the conjugate in the presence of these and other ligands are now reported. The correlation times of monomeric phospholipase A2 were shorter than expected for a hydrated, 13,000 molecular weight protein, indicating a high degree of probe mobility. The increase in the enzyme correlation time upon phospholipid addition was found to be consistent with the formation of a phospholipase A2 dimer or higher-order aggregate. It was found that activator lipids, such as phosphatidylcholine, increase the correlation time and probably the size of the enzyme, while nonactivator lipids, such as phosphatidylethanolamine, did so to a lesser extent. This suggests a possible link between aggregation and phosphatidylcholine-induced activation of this enzyme. PMID- 3337834 TI - Fat pad triacylglycerol fatty acid loss and oxidation as indices of total body triacylglycerol fatty acid mobilization and oxidation in starving mice. AB - We tested our hypothesis that, kinetically, triacylglycerol fatty acids in heterogeneously labeled adipocytes behave similarly to the whole fat pad triacylglycerol fatty acid during starvation in mice. Adipose triacylglycerol fatty acids were labeled with [1-14C]palmitate (complexed to albumin) by injection of a small bolus (2-5 microliter) into either epididymal or inguinal fat pads. Both 14C-labeled triacylglycerol fatty acid spec. act. and breath 14CO2 spec. act. were monitored 30 min after tracer injection and after 24-72 h starvation. Adipose triacylglycerol fatty acid spec. act. remained approximately constant during fasting, i.e., tracer and mass disappeared at similar rates. Negligible translocation of labeled triacylglycerol fatty acid from the injection site to other parts of the same fat pad or to distant fat pads occurred. Triacylglycerol fatty acid was mobilized more slowly from epididymal than from inguinal fat pads in two of three studies. Triacylglycerol fatty acid disappearance (loss) from inguinal fat pads was more replicable than from epididymal fat pads and more closely reflected the fall in whole body total lipid during starvation. The estimated percent of breath CO2-carbon derived from adipose triacylglycerol fatty acid increased from an average of approx. 32% in the postabsorptive state to about 77% after 48 h starvation. The data help to validate the direct tracer injection technique as a means of studying adipose triacylglycerol fatty acid turnover and oxidation. This approach should be particularly useful for studying the fate of adipose triacylglycerol fatty acid when it is mobilized. e.g., during states of inanition and starvation and in response to hormones and cancer-induced cachexia. PMID- 3337836 TI - Competition between chylomicrons and their remnants for plasma removal: a study with artificial emulsion models of chylomicrons. AB - In previous studies, protein-free emulsions of defined lipid composition were shown capable of simulating either the metabolism of chylomicrons (chylomicron like emulsion) or their remnants (remnant-like emulsion), depending on the content of free, unesterified cholesterol. To validate further the assumption that remnant-like and chylomicron-like emulsion have metabolic pathways in common with their natural counterparts, studies of competition for plasma removal were undertaken: the remnant-like emulsion labeled with [3H]triolein was injected sequentially twice in the carotid arteries of rats to compare the clearance of remnant-like emulsion of the second injection with the first (control). Prior to the second injection, a large bolus of the chylomicron-like emulsion or rat lymph chylomicron was injected, to check the hypothesis that remnant generated from chylomicron-like emulsion or natural chylomicrons could compete with and displace remnant-like emulsion particles from their tissue receptor sites. Experiments were also performed in rats treated with Triton WR-1339, to block the generation of remnants. Results showed that remnants derived from either natural chylomicrons or chylomicron-like emulsion both strongly competed with the remnant like emulsion. In contrast, when transformation of remnants was prevented by Triton, the undegraded particles of chylomicron-like emulsion or natural chylomicron were unable to compete with or displace remnant-like emulsion from its sites of removal from the plasma. In agreement with plasma clearance data, the hepatic uptake of the remnant-like emulsion was inhibited by the surplus dose of natural chylomicrons. In contrast, the spleen uptake was unaffected by it. PMID- 3337835 TI - Regulation of surfactant phospholipid secretion from isolated rat alveolar type II cells by lectins. AB - The major surfactant-associated protein is a potent inhibitor of surfactant phospholipid secretion from isolated type II cells. Since the major surfactant associated protein contains a carboxy terminal polypeptide domain which is homologous to the lectin-like liver mannose-binding protein, we tested whether lectins inhibit surfactant phospholipid secretion from rat alveolar type II cells. Concanavalin A, wheat germ agglutinin and Maclura pomifera agglutinin were potent inhibitors of surfactant phospholipid secretion. When adenosine 5' triphosphate (ATP) was utilized as a secretagogue, the IC50 values for inhibition of surfactant phospholipid secretion were 5.10(-7) (wheat germ agglutinin), 1.10( 6) (concanavalin A) and 2.5.10(-5) M (M. pomifera agglutinin). Similar results were obtained when 12-O-tetradecanoylphorbol 13-acetate was utilized as a secretagogue: IC50 values of 1.10(-6) M for concanavalin A and wheat germ agglutinin and 2.5.10(-5) M for M. pomifera agglutinin. Hapten sugars were utilized to antagonize the inhibitory effect of the lectins. N-Acetyl-D glucosamine significantly reversed inhibition of phospholipid secretion by wheat germ agglutinin in a dose-dependent fashion and methyl alpha-D-mannoside significantly reversed inhibition of phospholipid secretion by concanavalin A. N Acetyl-D-galactosamine had no significant effect on inhibition of secretion produced by any of the lectins. The inhibitory effect of the lectins did not appear to be due to cytotoxicity since lactate dehydrogenase was not released above control levels and the inhibition of the surfactant phospholipid secretion by wheat germ agglutinin could be reversed after treatment of cells with wheat germ agglutinin by washing the lectin from the cells followed by treatment of the cells with ATP. These studies demonstrate a direct inhibitory effect of plant lectins on phospholipid secretion from type II cells in vitro. PMID- 3337837 TI - Rat proximal small intestinal Golgi membranes: lipid composition and fluidity. AB - The present studies were conducted to examine and characterize the lipid composition and physical state of the membrane lipids of rat proximal small intestinal Golgi membranes. Golgi membranes were purified from isolated enterocytes; lipids were extracted from these membranes and analyzed by thin layer and gas-liquid chromatography. The 'static' and 'dynamic' components of fluidity of Golgi membranes and their liposomes were assessed by steady-state fluorescence polarization techniques utilizing r infinity and S values of 1,6 diphenyl-1,3,5-hexatriene and r values of DL-2-(9-anthroyl)- and DL-12-(9 anthroyl)stearic acid, respectively. Additional studies were also performed on these membranes, using benzyl and methyl alcohol, to examine the relationship between alterations in lipid fluidity and glycosphingolipid glycosyltransferase activities. The results of these studies demonstrated that: (1) the principal phospholipids and neutral lipids of intestinal Golgi membranes, respectively, were phosphatidylcholine, phosphatidylethanolamine and sphingomyelin, and unesterified cholesterol and fatty acids; (2) the major fatty acids of Golgi membranes were palmitic (16:0), stearic (18:0), linoleic (18:2), arachidonic (20:4) and oleic (18:1) acids; (3) fluorescence polarization studies using diphenylhexatriene detected a thermotropic transition at 24-26 degrees C in Golgi membranes and liposomes prepared from lipid extracts of these membranes; (4) benzyl alcohol (25 and 50 mM) but not methyl alcohol (50 mM) significantly increased the fluidity of these membranes; and (5) at these same concentrations, benzyl alcohol was also found to increase significantly the specific activity of UDP-galactosyllactosylceramide galactosyltransferase but not CMP-acetylneuraminic acid: lactosylceramide sialyltransferase. Methyl alcohol was not found to influence either enzyme's activity in these membranes. PMID- 3337838 TI - Glycosphingolipids of cultured human colon carcinoma cells and their drug resistant sublines. AB - Human colon carcinoma cells were analyzed for lipid phosphorus, cholesterol and glycosphingolipids. Ceramide mono-, di- and trihexosides and sulfatides were isolated by column and thin-layer chromatography and determined quantitatively on the basis of their hexose content. The complex lipid fractions so isolated were only partially resolved with the material available. Gangliosides GM2 and GM3 and globoside were major components of the fraction and were determined on the basis of their hexose, hexosamine and neuraminic acid content. The HCT 116, 116a and 116b cells contained no fucolipids. Cell lines resistant to mitomycin C, teniposide and etoposide were developed and analyzed. Over the 5 year period of the study sulfatides declined to about one-fourth of their original amounts in both parent and drug-adapted cells. HCT 116 cells adapted to mitomycin C and teniposide had 30% less ceramide monohexoside and a 45% greater cholesterol to lipid phosphorus ratio than the parent cells. Reductions in ceramide dihexoside in the drug-adapted cells were greater than those of the ceramide monohexoside. Galabiosyl ceramide was the major ceramide dihexoside in all the cells and accumulated in HCT 116a to levels 4-6-fold greater than that of the other lines as the only dihexoside. PMID- 3337839 TI - Postnatal transformations of alveolar surfactant in the rabbit: changes in pool size, pool morphology and isoforms of the 32-38 kDa apolipoprotein. AB - To clarify perinatal transformations of surfactant we performed lung lavage in term fetuses and in 0-24-h-old newborn rabbits. Lavage fluid was separated into three pools, namely lavage pellet, lavage supernatant and cells. We found that at birth the pellet contains 94.1 +/- 1.4% (S.E.) saturated phosphatidylcholine, while the supernatant and cells contain traces of it. At birth the pellet contains secreted lamellar bodies while the supernatant lacks any recognizable structure. After birth, the alveolar saturated phosphatidylcholine level increases 5.1-times in 24 h, the proportions between pools reaching adult values in 90 min (pellet = 75.9 + 4.8%, supernatant = 22.7 +/- 4.9%), and small vesicles appear in the supernatant, probably originating from the turnover of alveolar surfactant during breathing. The saturated phosphatidylcholine associated with cells remains unchanged. At birth, the 32-38 kDa surfactant apolipoprotein appears to be less extensively sialylated than in adult life. PMID- 3337840 TI - Glycerol metabolism in type II pneumocytes isolated from streptozotocin-diabetic rats. AB - Glycerol utilization for phospholipid biosynthesis was examined in type II pneumocytes isolated from normal and streptozocinin-diabetic rats. With glucose in the incubation medium, incorporation of exogenous [1,3-14C]glycerol into disaturated phosphatidylcholine, total phosphatidylcholine (PC), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE) was increased 4-fold in cells from diabetic rats. In the absence of glucose, glycerol incorporation was 5-fold greater than in its presence in cells from normal animals, but was further increased 2.2-fold in cells from diabetic rats. Insulin treatment of diabetic rats returned all incorporation rates to control values. The increased glycerol incorporation rates were not due to differences in either phospholipid turnover or the size of the glycerol 3-phosphate precursor pool. Kinetic analysis of glycerol entry into the acid-soluble cell fraction indicated that glycerol transport occurred largely by simple diffusion, and was not rate limiting for its entry into lipids. Glycerol entry into the total lipid fraction was saturable, reaching a Vmax of 48 pmol/micrograms DNA per h in normal cells and 120 pmol/micrograms DNA per h in cells from diabetic rats, with no change in the Km (0.31 mM). While glycerol oxidation was reduced 23% in cells from diabetic rats in the presence of glucose and by 44% in the absence of glucose, glycerol kinase activity in sonicates of cells from diabetic animals was increased 210% and was reversed by in vivo insulin treatment. These results suggest that glycerol utilization in type II pneumocytes is a hormonally regulated function of both glycerol oxidation and glycerol phosphorylation. PMID- 3337841 TI - Fatty acid specificity of the lysosomal acid cholesterol esterase in intact human arterial smooth muscle cells. AB - The fatty-acid specificity of the lysosomal cholesterol esterase was examined in cultured human arterial smooth muscle cells. The lysosomal compartment of cultured cells was enriched with cholesteryl esters by incubation of cells with 0.2 mg/ml low-density lipoprotein and 50 microM chloroquine for 24 h. The hydrolysis of cholesteryl esters was subsequently induced by incubating cells in a medium containing 5% lipoprotein-deficient serum without chloroquine. Cellular cholesteryl ester mass was markedly reduced after 23 h in the lipoprotein deficient serum. Fatty-acid analysis of cholesteryl esters in cells before and after the 23 h incubation with lipoprotein-deficient serum revealed that polyunsaturated cholesteryl esters (linoleate and arachidonate) were preferentially hydrolyzed compared to cholesteryl oleate or saturated cholesteryl esters. An increase in the ratio of cholesteryl oleate to cholesteryl linoleate was observed even when the cellular activity of acyl-CoA:cholesterol acyltransferase was inhibited with Sandoz Compound 58-035. We conclude that, in human arterial smooth muscle cells, the lysosomal acid cholesterol esterase preferentially hydrolyzes polyunsaturated cholesteryl esters. PMID- 3337842 TI - Phosphorylation of multiple sites in a 15,000 dalton proteolipid from rat skeletal muscle sarcolemma, catalyzed by adenosine 3',5'-monophosphate-dependent and calcium/phospholipid-dependent protein kinases. AB - This study reports a partial characterization of a 15,000 dalton (15 kDa) proteolipid present in rat skeletal muscle sarcolemma. The proteolipid is phosphorylated by both cyclic AMP-dependent and calcium/phospholipid-dependent protein kinases, displays an isoelectric point (pI) of 5.9, and can be extracted from sarcolemma by acidified chloroform/methanol (2:1) or non-ionic detergents. Phosphoamino acid analysis and tryptic fingerprinting of the phosphorylated proteolipid indicate that both cyclic AMP- and calcium/phospholipid-dependent protein kinases predominantly phosphorylate serine residue(s) on a single tryptic peptide. Additivity experiments and thermolytic fingerprinting demonstrate a minimum of two distinct phosphorylation sites on the proteolipid, the phosphorylation of which is independently catalyzed by cyclic AMP-dependent and calcium/phospholipid-dependent protein kinases in vitro. This sarcolemma proteolipid, which appears to be identified to a sarcolemma protein previously reported to be phosphorylated upon addition of insulin in a GTP-dependent manner (Walaas, O., Walaas, E., Rye-Alertsen, A. and Horn, R.S. (1979) Mol. Cell. Endocrinol. 16, 45-55), therefore represents a possible membrane target for those neuronal and hormonal stimuli which can regulate cyclic AMP-dependent or calcium/phospholipid-dependent protein kinase activities in skeletal muscle. PMID- 3337843 TI - Vascular smooth muscle cells synthesize, secrete and express coagulation factor V. AB - Expression of cellular procoagulant activity may be one of the more important responses to vascular injury. Because factor V, a coagulation cofactor in the prothrombinase complex, catalyzes the conversion of prothrombin to thrombin, it may be a key to understanding this response. Therefore, we have investigated the synthesis, secretion and expression of factor V by vascular smooth muscle cells, which proliferate at sites of vascular injury. Cultured aortic vascular smooth muscle cells constitutively secreted Factor V activity, as determined by a functional assay. Labeled factor V was immunoprecipitated from conditioned medium of [35S]methionine-labeled cells, indicating that the secreted factor V was synthesized by vascular smooth muscle cells. Treatment of vascular smooth muscle cells with tunicamycin prevented secretion of factor V, suggesting that its secretion was dependent on the presence of N-linked carbohydrate. Factor V activity was also expressed on the vascular smooth muscle cell surface, as indicated by the ability of cultured cells to promote factor Xa-catalyzed prothrombin activation. These data suggest that the proliferation of smooth muscle cells in response to vascular injury may be one mechanism that links vascular disease with thrombosis. PMID- 3337844 TI - Iron mobilization from cultured rat bone marrow macrophages. AB - The reticuloendothelial system is responsible for removing old and damaged erythrocytes from the circulation, allowing iron to return to bone marrow for hemoglobin synthesis. Cultured bone marrow macrophages were loaded with 59Fe labelled erythroblasts and iron mobilization was studied. After erythroblast digestion, iron taken up by macrophages was found in ferritin as well as in a low molecular-weight fraction. The analysis of iron mobilization from macrophages shows: (1) the iron was mobilized as ferritin. (2) A higher mobilization was observed when apotransferrin was present in the culture medium. (3) In the presence of apotransferrin in the culture medium, part of the iron was found as transferrin iron. (4) Iron transfer from ferritin to apotransferrin was observed in a cell-free culture medium and this process was temperature independent. The results indicate that after phagocytosis of 59Fe-labelled erythroblasts by macrophages, iron is mobilized as ferritin. In the plasma, this iron can be transferred to apotransferrin. PMID- 3337845 TI - Inhibition of cyclic AMP-dependent protein kinase by the polar head group of an insulin-sensitive glycophospholipid. AB - A glycophospholipid has been purified from rat liver membranes and shown to copurify with an insulin-sensitive glycophospholipid isolated from H35 hepatoma cells. The polar head group of this glycophospholipid is a phospho oligosaccharide generated by treatment with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. It has been proposed that this phospho-oligosaccharide, which is also generated in response to insulin, may play a role in insulin action. Incubation of the catalytic subunit of cyclic AMP dependent protein kinase with this phospho-oligosaccharide inhibited the activity of the kinase to phosphorylate histone IIA, a purified preparation of phospholipid methyltransferase and kemptide, a phosphate-accepting peptide. Inhibition of kinase activity was dose-dependent and 50% inhibition of histone phosphorylation was demonstrated with a concentration of phospho-oligosaccharide of around 2 microM. This effect was demonstrated in the presence of ATP at concentrations up to 1 mM, indicating that the phospho-oligosaccharide acts at physiological concentrations of ATP and that it does not compete with this nucleotide for the same binding site in the kinase. Inhibition by the phospho oligosaccharide of kinase activity could be reversed by dilution or dialysis and was not reproduced by up to 50 microM myo-inositol, glucosamine, galactose, myo inositol 1-phosphate, glucosamine 1-phosphate, galactose 1-phosphate or phosphorylcholine. The inhibitory activity was resistant to mild acid treatment but was labile to treatment with alkali, exposure to nitrous acid or incubation with sodium periodate. The phospho-oligosaccharide had no effect on the phosphorylation of lysine-rich histone by rat brain protein kinase C and on the binding of cyclic AMP to a cyclic AMP-dependent protein kinase. In conclusion, the data in this study suggested that a phospho-oligosaccharide generated from an insulin-sensitive glycophospholipid may play a role in insulin action by modulating cyclic AMP-dependent protein kinase activity. PMID- 3337846 TI - Vasoactive intestinal peptide stimulates glycolysis in pituitary tumours; 1H-NMR detection of lactate in vivo. AB - 1H- and 31P-NMR spectroscopy has been applied to rats carrying implanted tumours in vivo, and used to observe simultaneous changes in intracellular pH (pHi) and lactate concentration during the stimulatory action of vasoactive intestinal polypeptide (VIP). A maximal decrease in pHi to a mean of 0.29 units below basal values was recorded. At the same time, 11 min after VIP, a maximal increase in tumour lactate was found, with a mean value of 150% of the basal concentration. The magnitude of these changes was compatible with in vitro measurements of basal lactate concentration and buffering capacity made on the same tumour line. It is concluded that VIP stimulates glycolysis by the tumour cells, resulting in an accumulation of lactate and a consequent fall in pHi. PMID- 3337847 TI - How does doxorubicin interfere with actin polymerization? AB - It is well known that doxorubicin (adriamycin), an antibiotic with an antitumoral action, has some undesirable side effects. Among these, the most serious is, undoubtedly, damage to myocardial tissue (progressive cardiomyopathy). We have for some time focused our attention on the effect of this drug on cellular contractile systems and, more specifically, on the process of actin polymerization, which we consider to be an extremely delicate key point for the economy of most cellular motor manifestations. In the present study, using capillary viscometry, spectrofluorometry and electron microscopy, we have shown a negative action of doxorubicin on various important chemical events which contribute to the transformation of G-actin into F-actin. Specifically, we found that the drug mainly acts by reducing the polymer size. A possible action mechanism of the antibiotic is proposed and a plausible correlation among the events described in vitro and those observed in vivo is advanced. PMID- 3337848 TI - Rat antibodies as probes for the characterization of progesterone receptor A and B proteins from laying hen oviduct cytosol. AB - The chicken oviduct contains two different hormone binding forms of the progesterone receptor, A and B. We have prepared rat antisera against both forms of the receptor partially purified from laying hen oviduct. The anti-progesterone receptor A antiserum reacts with both receptor forms on Western blots, while the anti-progesterone receptor B antiserum reacts mainly with the B form. Both antisera also react with the native progesterone receptor proteins as shown by sedimentation analysis of the antibody-receptor complexes. Receptors A and B are recognized on Western blots of total protein from dissolved tissue, indicating that both forms are likely to be physiological components. Epitope mapping experiments show that immunogenicity of both receptor molecules is restricted to structurally related protein domains of 28 kDa in receptor A and of 52 kDa in receptor B. PMID- 3337849 TI - Are statistics necessary? PMID- 3337850 TI - Pharmacological modulation of cortisol secretion and dexamethasone suppression in Alzheimer's disease. AB - We have investigated the dexamethasone suppression of cortisol release in a group of 28 patients with senile dementia of the Alzheimer type (SDAT) after stimulation by physostigmine and clonidine, as compared with basal conditions. All patients but one had previously been evaluated with a depression symptom checklist and had submitted to a standard Dexamethasone Suppression Test (DST). SDAT patients showed normal baseline cortisol values measured at 4:00 PM. DST was reproducible, but nonsuppression did not appear to be a feature of the disease, nor of the dementia syndrome, although a majority of the most demented patients were found to be nonsuppressors. Physostigmine stimulated cortisol secretion in 20 of 24 cases, irrespective of the severity of dementia. Clonidine induced a secretion in 12 of 15 cases, but this was less than that observed after cholinergic stimulation. Physostigmine made cortisol release significantly less sensitive to the suppressive effect of dexamethasone than clonidine in SDAT. This double response should be tested as a possible predictor of a cholinergic therapeutic effect. PMID- 3337852 TI - Visible persistence in paranoid schizophrenics. AB - A visual temporal integration (i.e., visible persistence) task was performed by normal controls and paranoid schizophrenics. The task evaluated the critical duration (CD), which approximates the duration of peripheral persistence duration and post-CD persistence, which is possibly more associated with central processes. Subjects were required to report when temporally modulated spatial frequency patterns, which are known to have characteristic temporal processing rates, were pulsing "on-off" with a distinct "off" period. The dependent measure was the duration of visible persistence. An analysis of groups X spatial frequency duration (50, 75, 150, 300 msec) X spatial frequency (high, medium, low), with repeated measures on the last two variables, revealed that the second order interaction was significant (p less than 0.05). Schizophrenics had shorter visible persistence only for the 300-msec presentation for the high spatial frequency pattern. Also, the CD of schizophrenics did not conform to the duration of normals on the high spatial frequency. The results are discussed in terms of the role high spatial frequencies plays in visual information processing and how shorter visible persistence by paranoid schizophrenics may reflect a premature termination of information necessary for synthesis into accurate percepts. PMID- 3337853 TI - Frontal midline theta activity and platelet MAO in human subjects. AB - The distinctive theta rhythm that appears at the frontal midline during the performance of mental tasks has been designated as frontal midline theta (Fm theta). Fm theta shows individual differences and seems to be related to certain personality traits. In several studies, it has been indicated that low platelet monoamine oxidase (MAO) activity is also associated with certain personality traits. In the present study, we found a negative correlation between the appearance of Fm theta and platelet MAO activity. Subjects with marked extroversion show a high amount of Fm theta and low MAO activity. It is therefore suggested that Fm theta, an electrophysiological marker, may be useful in the investigation of monoamine functions in the central nervous system (CNS) by way of platelet MAO activity, a biochemical marker. PMID- 3337851 TI - Treatment of psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome) using lithium and phenytoin. AB - Six patients [5 men and 1 woman, mean age 37.3 +/- 8.2 (SD) years] with psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome) underwent a sequence of treatments in an effort to normalize basal serum sodium levels and thereby protect the patients against complications, including hyponatremic seizures and coma. The morning baseline group mean basal serum sodium value was 132.5 +/- 3.8 meq/liter. Over a 20-month period, the sequence of treatments was salt-added diet, lithium and phenytoin, and lithium alone. Each treatment program yielded morning group mean basal serum sodium determinations superior to baseline values, except for the program of lithium alone, which could not be tolerated. The combination of lithium and phenytoin provided a morning group mean basal serum sodium level of 140.6 +/- 3.2 meq/liter, which was superior (p less than 0.01) to all other treatment modalities. Early morning hyposthenuria persisted throughout the 20-month period of observation. PMID- 3337854 TI - Platelet MAO deamination of serotonin in depressed patients. Changes after imipramine treatment and clinical correlations. AB - Monoamine oxidase (MAO) in blood platelets has been used as a model to study MAO in the central nervous system, where disorders in serotonergic systems are thought to occur in depression. Inconsistent changes in platelet MAO of depressed patients have been reported when several substrates other than serotonin (5-HT) have been used. To correlate changes in platelet MAO activity with the enzyme activity in central serotonergic systems, the platelet MAO activity of depressed patients (first unmedicated and then after 3 weeks and 2 months of imipramine treatment) and normal controls was measured using 5-HT as substrate. The results showed that there is a steady, measurable platelet MAO activity with that substrate. This activity was significantly higher in unmedicated depressed patients than in controls, and it decreased progressively with imipramine treatment, reaching a normal level when the patients were clinically recovered from depression after 2 months of therapy. PMID- 3337855 TI - Why you should avoid statistics. PMID- 3337856 TI - Altered conversion of tryptophan to kynurenine in newly abstinent alcoholics. PMID- 3337857 TI - Effect of tobacco withdrawal on the dexamethasone suppression test. PMID- 3337858 TI - Sleep architecture in anorexia nervosa and bulimia. PMID- 3337859 TI - Conflicts of interest. PMID- 3337860 TI - Neurochemical changes in rat brain amines after short- and long-term inhibition of monoamine oxidase by a low dose of tranylcypromine. AB - The effects of short- and long-term administration of a low dose of tranylcypromine on brain and urine levels of several biogenic amines and on brain activity of monoamine oxidases (MAO) A and B were investigated. MAO-A and MAO-B were inhibited by greater than 85% on day 1, and this inhibition continued to increase over the course of the study (42 days). Levels of 5-hydroxytryptamine in brain continued to increase up to day 21 and did not decline from day 21 to day 42, and levels of tranylcypromine itself continued to increase up to day 42. Dopamine concentrations peaked at day 10 and were not significantly different from that value by day 42. Brain levels of tryptamine and beta-phenylethylamine showed dramatic elevations after the first dose of the drug and remained essentially unchanged from those high values throughout the course of the drug treatment. Brain and urine increases in tryptamine and beta-phenylethylamine showed similar patterns, whereas urinary 5-hydroxytryptamine excretion reached maximal levels earlier than did brain levels. PMID- 3337861 TI - The dexamethasone suppression test and plasma dexamethasone in generalized anxiety disorder. AB - A Dexamethasone Suppression Test nonsuppression rate of 27% was found in a group of 30 generalized anxiety disorder patients before treatment. The dexamethasone concentrations in the eight nonsuppressors were significantly lower than in eight suppressors matched by sex and age, but were similar to those in five nonsuppressors from a matched normal control group. The dexamethasone concentrations in the generalized anxiety disorder suppressors and a matched group of eight normal control suppressors were similar. After successful nondrug behavioral treatment, all generalized anxiety disorder patients were suppressors. Posttreatment dexamethasone concentrations in the initial nonsuppressor patients remained significantly lower than in the initial suppressors. The results suggest that low plasma dexamethasone concentrations after 1 mg oral dexamethasone may confer a vulnerability to nonsuppression that may be expressed in the presence of high state anxiety. PMID- 3337862 TI - Cornell Scale for Depression in Dementia. AB - The Cornell Scale for Depression in Dementia is introduced. This is a 19-item clinician-administered instrument that uses information from interviews with both the patient and a nursing staff member, a method suitable for demented patients. The scale has high interrater reliability (kw = 0.67), internal consistency (coefficient alpha: 0.84), and sensitivity. Total Cornell Scale scores correlate (0.83) with depressive subtypes of various intensity classified according to Research Diagnostic Criteria. PMID- 3337864 TI - Increased CSF amino acids and ventricular enlargement. PMID- 3337863 TI - Bilateral brain dysfunction during motor activation in type II schizophrenia measured by EEG mapping. AB - In this final electroencephalographic (EEG) mapping study of our series on motor dysfunction in neuroleptic-treated schizophrenic patients, we studied 10 right handed patients with marked negative symptomatology [type II; raw score on the SANS (Munich version) 31.4 +/- 5.1]. Simple and multisensorimotor tasks involving both the dominant and nondominant hand were used for cortical activation. All tasks were referred to resting states obtained after specially designed relaxation procedures. In contrast to predominantly type I patients (SANS-MV score 12.3 +/- 4.9) of our previous EEG mapping studies, we found for resting states minor evidence (only) of increased power values in the frequency bands delta and theta. Furthermore, in contrast to signs of "left hemisphere dysfunction" and possible "compensatory right hemisphere overactivation" during motor tasks, which we discussed previously for our type I patients, we found for the type II schizophrenics a bilateral brain dysfunction. This consisted of "nonreactivity" in all frequency bands except alpha, in which, on the contrary, a "hyperreactivity" seemed to be present. In combination with evidence of bilateral hemispheric dysfunction in type II patients reported by other authors using EEG, evoked potentials, regional cerebral blood flow (rCBF) and magnetic resonance imaging (MRI) methods, this suggests that marked bilateral brain dysfunction may be correlated in schizophrenia with a clinical syndrome corresponding rather to the "negative pole" of the positive-negative dimension. In contrast, "left hemisphere dysfunction" and "signs of compensatory overactivation" seem to be linked more to a "positive" symptomatology. Finally, discrepancies of our EEG mapping and rCBF findings during motor activity suggest, speculatively, "uncoupling" between electrical and circulatory parameters in schizophrenia involving both hemispheres in type II, and predominantly the left hemisphere in type I, patients. PMID- 3337865 TI - Occipital slow EEG rhythms (3-6 Hz activity), an unreliable marker. PMID- 3337866 TI - Neuroleptic malignant syndrome, amitriptyline, and thioridazine. PMID- 3337867 TI - Physostigmine, auditory P300, and Alzheimer's disease. PMID- 3337868 TI - [Immunocytochemical localization of tryptophanyl-tRNA-synthetase in a line of bovine kidney cells and in sublines with elevated enzyme levels]. AB - Intracellular localization of tryptophanyl-tRNA synthetase (E. C. 6.1.1.2) has been studied immunocytochemically using monospecific antibodies in cultured bovine kidney cells (strain MDBK) and in substrains with elevated enzyme levels. Both light and electron microscopy were used and native or detergent-treated cells were examined. The product of cytochemical reaction was revealed on free polyribosomes, polyribosomes attached to membranes of granular endoplasmic reticulum, on cytofilaments and in the nucleus as well. PMID- 3337869 TI - [Morphological changes in the liver in acute galactosamine poisoning with different protein levels in the diet]. AB - Changes in hepatocyte ultrastructure after galactosamine administration to rats adapted to diets with different protein content have been studied. Typical galactosamine effects on hepatocytes were manifested earlier in animals on low and high protein diets. At the same time a considerable decrease in protein synthesis led to insufficient expression of the reparative processes in all the observed groups of animals. PMID- 3337870 TI - [Blood rheology and microcirculation in the dynamics of acute experimental pancreatitis]. AB - The results of the experiments performed on 63 rabbits with experimentally induced acute pancreatitis made it possible to conclude that this pathology was accompanied by considerable hemorheological and microcirculatory disorders. The degree of hemorheological deviations was shown to correlate with the severity of acute pancreatitis. PMID- 3337871 TI - [Changes in the function and energy metabolism of the myocardium in experimental diabetes mellitus in dogs]. AB - Coronary arteries, coronary sinus, heart cavities, and great vessels were catheterized in anesthetized dogs with alloxan diabetes. Cardiac contractility, coronary and systemic circulation, myocardial energy metabolism and acid-base balance were studied. It was shown that the alterations of the cardiac function occurred in experimental dogs with severe diabetes mellitus. They consisted of a decrease in cardiac and working outputs, ejection period, maximum velocity of the left ventricular contractions and an increase in the projection period. These dysfunctions were caused by the alterations of the myocardial energy metabolism and systemic changes in the acid-base balance. PMID- 3337872 TI - [Effect of drugs on the resistance of the myocardium to hypoxia]. AB - A method for the investigation of drug effects in the myocardium resistance to hypoxia has been suggested. It is based on the determination of drug effects on the performance of the isolated spontaneously contracting atrium (ISCA) of rats under hypoxic conditions. Hypoxia was induced by oxygen displacement from the nutritional solution by nitrogen. ISCA resistance to hypoxia was assessed by the mechanogram of the heart preparation (the duration and volume of ISCA performance being up to 50% of the initial amplitude). Using the inhibitor analysis, it has been demonstrated that the given model of myocardial hypoxia adequately reflects the role of energy cellular metabolism in the regulation of ISCA resistance to hypoxia and can be used in the search for myocardial antihypoxic agents. PMID- 3337873 TI - [Development of diabetes mellitus in the progeny of 6 generations of female rats with alloxan diabetes]. AB - The development of diabetes mellitus has been studied in six progeny generations of female Wistar rats with alloxan diabetes coupled with normal males. An increased incidence of diabetes and its higher degree have been observed in younger generations studied. A correlation has been established between the frequency of diabetic type of glucose tolerance and hypoglycemia in rats of the first generation during the first month of their postnatal life, and the incidence of diabetes in the progeny of mother rats from the older generations. PMID- 3337874 TI - [Viral hepatitis A in lower Old World monkeys (possibility of use as a model for vaccine testing)]. AB - Morphological, virological and serological data characteristic of spontaneous hepatitis A in macaques and green monkeys have been presented. The disease similar to human hepatitis A was induced in M. iris macaques, with the virus isolated from spontaneously infected rhesus monkeys. Experimental model of hepatitis A in macaques is likely to be used for the testing of vaccines and antiviral preparations. PMID- 3337875 TI - [Systemic arterial pressure and characteristics of its changes in response to hypertensive agents in tumor-bearing animals]. AB - Arterial pressure (in the carotid artery determined by electromanometry) and total peripheral resistance (changes in the clear space of resistive arteries of the mesenterium, skeletal muscles and mammary glands measured by biotelemicroscopy) were studied in tumor-bearing animals (random bred, BALB/c and CBA mice with Ehrlich carcinoma). With the growth of hypodermic injected tumor, it has been shown that the arterial pressure first dropped and then there was a tendency towards normalization, but the pressure never reached the initial level. At the same time arterial dilatation took place, especially at the first stage of tumor growth. This shows the dependence of changes in arterial pressure on the clear space of resistive arteries. It was also revealed that changes in the vascular tone were connected with the functional disturbances of adrenoactive structures but not with reduced myocyte contractility. PMID- 3337877 TI - [Effect of an ultrahigh-frequency electromagnetic field on the heat conductivity of experimental biological tissue]. AB - It has been established that heat conductivity was markedly increased after UHF irradiation. The combined use of UHF-irradiation and cryogenic destruction is 30 40 times as effective as cryogenic destruction alone. PMID- 3337876 TI - [Mechanism of the development of thioridazine retinopathy]. AB - Comparative electron microscopic, electrophysiological and biochemical studies of thioridazine influence on lipid peroxidation in vivo (rats, rabbits) and in vitro (model systems) were performed. It was shown that thioridazine retinopathy was not followed by an increase in lipid peroxidation and antioxidant (dibunol) failed to protect the retina against the destructive action of thioridazine. Moreover, thioridazine inhibited lipid peroxidation in model system. PMID- 3337878 TI - [Metabolism of glycoproteins and fibronectin in skin fibroblasts of patients with rheumatoid arthritis]. AB - The distribution in the cellular monolayer of the de novo synthetized pre-labeled glycoproteins and fibronectin upon culturing of fibroblasts in the medium with low serum content was analyzed. It was found that in rheumatoid arthritis (RA) the amount of total glycoproteins on the surface and within fibroblasts is higher and in the extracellular matrix is lower than in skin fibroblasts of healthy donors (HD). However, the amount of pre-labeled fibronectin on the surface of skin fibroblasts from patients with RA was considerably lower than in those from HD This finding as well as a rapid decrease in the amount of pre-labeled fibronectin in the extracellular matrix of RA fibroblasts is indicative of a more rapid metabolism of this protein in RA. In the skin fibroblasts from HD there was a practically uniform decrease in the amount of pre-labeled fibronectin in the cellular monolayer. The presence of caseinolytic activity in the culture medium even upon the first day of cell culturing in the serum-free medium, as well as the effect of various proteinase inhibitors on glycoprotein content in the cellular monolayer provide evidence that the rate of glycoprotein and fibronectin metabolism, especially in connective tissue cells of patients with RA, might possibly be determined not only by the level of their synthesis but also by the level of proteolytic activity in the connective tissue cells. PMID- 3337879 TI - [Antagonism of caerulein, a CCK-8 receptor agonist, to the behavioral effects of ketamine in mice and rats]. AB - It has been established in experiments on male mice and rats that caerulein antagonized the behavioural effects of ketamine, an agonist of phencyclidine receptors. Caerulein (75-375 micrograms/kg) and haloperidol (0.1-1.5 mg/kg) suppressed the stereotyped behaviour and motor excitation induced by ketamine (30 mg/kg) in mice. Caerulein and haloperidol failed to affect ketamine-induced ataxia. Caerulein (10 micrograms/kg) and the opioid antagonist naloxone (5 mg/kg) completely blocked the amnestic action of ketamine (30 mg/kg) in passive avoidance experiments on rats. It seems likely that the suppression of the behavioural effects of ketamine by caerulein is related to its functional antagonism with dopamine and opioid receptors. PMID- 3337880 TI - [Protective effect of lithium oxybutyrate on the ischemic myocardium]. AB - In the experiments on different animal species (mice, cats, dogs) lithium hydroxybutyrate has been shown to have antihypoxic and anti-ischemic effects. Lithium hydroxybutyrate improved the functional state of the ischemic myocardium, stimulated the accumulation of macroergic phosphates (ATP) in the heart, protected the ischemic myocardium and delayed the progression of the reversible ischemic damage into the irreversible one. The improvement of the collateral coronary circulation plays an important role in the anti-ischemic action of the drug. PMID- 3337881 TI - [Toxicologic evaluation of individual chemical compounds and complex mixtures using a motile cell test object]. AB - The possibility of quantitative prognosis of chemical compounds and complex mixtures toxicity by means of a biotechnical system with suspension of bull spermatozoa sensor was investigated. The concentration of some chemical compounds, inhibiting by half spermatozoa motility has been experimentally determined. A correlation between the values determined and acute toxicity of the compounds tested has been established. The possible use of the biotechnical system for the screening of medical polymer materials has been demonstrated. PMID- 3337883 TI - [Ability of the opiate kappa-agonist bremazocine to facilitate the flexor reflex of the right hindlimb in spinal rats]. AB - It has been found that bremazocine predominantly enhances the flexor reflex of the right hind limb, without affecting the left limb. The similarity of the visual data measuring the asymmetry of the pose and the asymmetry of EMG responses to painful stimulation has a high probability. No correlation between the asymmetry of the pose and EMG extensor activity has been found. PMID- 3337882 TI - [Macrophage activation induced by a synthetic antioxidant]. AB - The effect of a synthetic antioxidant 2-tretbutyl-3-hydroxypyridine (TBHP) on the function of murine peritoneal macrophages (MP) has been studied. A direct contact of TBHP with MP in vitro increased the activity of a key enzyme of glucose monophosphate graft--glucose-6-phosphate dehydrogenase and the proportion of flattened MP. as compared to the control. Upon intraperitoneal MP injection the number of MP's in the abdominal cavity of mice increased. They differed from control MP's in enhanced flattening and phagocytosis. In mice with preinduced defect of abdominal clearance TBHP contributed to the recovery of the normal level of antibacterial protection. In all the in vitro and in vivo tests studying its activating effect on MP, the synthetic antioxidant was not inferior to the standard MP activator--bacterial lipopolysaccharide. PMID- 3337884 TI - [Effect of alkylation and carbamoylation on the characteristics of genetic damage to mammalian somatic cells cultured in vitro]. AB - Genetic effects of alkylation alone and combined with carbamoylation were studied following treatment of CHO-AT3-2 Chinese hamster cell line with N-nitroso-N methylurea for 7 and 60 min. Gene mutations at HGPRT and Na+/K+-ATPase loci, micronuclei, cells with fragmented nuclei and lethality caused by NMU were recorded. Prolonged exposure to the mutagen made these effects more pronounced, particularly the fragmented nuclei and cell death. The combined action of the two mechanisms, therefore, enhanced the mutagenic effects of alkylation and expanded the range of DNA lesions towards greater incidence of gross damage to chromosomes and chromatids. PMID- 3337885 TI - [Isolation of DNA from epithelial cells of the internal portion of the cheek]. AB - It is suggested to use epithelial cells from the inner cheek surface as a source of high molecular individual genomic human DNA to be used in Southern hybridization. The method efficiency has been proved experimentally. PMID- 3337886 TI - [Mitotic activity of alveolar macrophages in nonspecific diffuse lung pathology]. AB - Endopulmonary cytograms and mitotic activity of alveolar macrophages (AM) in the bronchoalveolar lavage (BAL) from 30 patients with diffuse lung pathology have been studied. AM mitosis was found in 24 cases. Mitotic index for all the patients was 0.65% and ranged from 0.25 to 2.75%. Electron microscopy revealed the capacity of differentiated forms of AM for mitotic division. Free AM may be regarded as slowly proliferating cell population, capable of self-reproduction in lung pathology. PMID- 3337888 TI - [Inhibition of human granulocyte elastase by antibodies to leukocyte thermostable alpha-glycoprotein]. AB - The activity of granulocyte elastase (GE) was discovered in the preparations of leukocyte thermostable alpha-glycoprotein (LTG) isolated from pus by means of ion exchange chromatography. The activity of GE was determined according to MeoSuc(Ala)2ProValpNa hydrolysis. The antibodies against LTG were isolated from monospecific antisera. Sepharose with immobilized fraction of pus proteins was utilized as immunosorbent. Isolated antibodies to LTG inhibited the GE activity. An inhibitory effect of antibodies increased with the increase in their concentration. The identity or binding of LTG and GE was suggested. The binding of LTG with pus protein component was discovered, the biological meaning of this phenomenon being unknown. PMID- 3337887 TI - [Complete change of the cell composition of the liver parenchyma following exposure to dipin and partial resection]. AB - The phenomenon of total replacement of preexisting and damaged hepatocytes in mice were demonstrated by the method of autoradiography. Adult mice were injected an alkylating drug Dipin 2 h prior to partial hepatectomy and then proliferating cells were labelled by means of multiple injections of 14C-thymidine. Dipin in combination with mitotic stimulation induced multiple mitotic aberrations in proliferating hepatocytes resulting in degeneration, death and then elimination of prelabelled liver cells. New parenchymal tissue originated from non-labelled preneoplastic nodules. These hepatocyte nodules grew in size, propagated and 8-10 months later completely replaced the preexisting hepatocytes. PMID- 3337889 TI - [Ultrastructural organization of the endotheliocytes of iliac lymph node capillaries in pregnancy (morphometric study)]. AB - Using light and electron microscopy and morphometry, the morphological changes in the lymph nodes of arterial and venous parts of capillaries were studied on the 11th, 17th and 21st days of pregnancy in rats. Ultrastructural changes in endothelial cells of blood vessels in the uterine lymph nodes during normal pregnancy are of adaptive nature and are possibly responsible for the relief of the blood congestion in the system of the inferior vena cava and for the improvement of the utero-placental circulation. PMID- 3337890 TI - [Morphofunctional evaluation of the condition of the brain in rats with different degrees of recovery of neurological status following arrest of systemic blood circulation]. AB - The brain status was studied for four days after resuscitation of rats with different degrees of recovery of the neurological status after systemic circulatory arrest induced by the occlusion of vascular bundles of the heart. Morphometric analysis of the population of Purkinje cells from the two different functional zones of the cerebellum revealed that in comparison with completely recovered rats, the animals with disturbed neurological status were characterized by loss of neurons, disturbed composition of the neuronal population, development of severe dystrophic cell changes. The lateral zone of the cerebellum hemisphere was most affected. Four days after resuscitation all the animals showed a sharp increase in the size of the nucleus of Purkinje cells, which is considered to be one of the mechanisms of neuronal adaptation to hypoxia. PMID- 3337891 TI - [Arterialization of the venous system of the brain]. AB - The possibility of reverse perfusion of the brain (in which arterial blood flows to brain tissues through venous vessels, and venous blood is drained by the arteries) was studied in acute and chronic experiments on dogs. Blood pressure in cerebral veins could reach 90--120 mm Hg, in Willisii arteries it was 5--35 mm Hg. Liquor pressure reached 20--35 mmHg. After temporary arterialization of the brain venous system (10, 30 and 60 min) the animals survived without impairment of the brain function and behaviour. In the future reverse perfusion of the brain (in which blood pressure in the arteries falls to the level of venous pressure) could be used as a means of urgent surgical intervention in cases of threatened or beginning intracranial arterial hemorrhage. PMID- 3337892 TI - [Development of the connective tissue in the wall of the rabbit aorta in experimental atherosclerosis]. AB - Structural and functional characteristics of cells involved in collagen synthesis have been studied in experimental hypercholesterolemia in rabbits. Autoradiographic studies, using 3H-proline and 14C-hydroxyproline have demonstrated that collagen synthesis takes place only in the intima in the area of cellular proliferation. At earlier stages of experimental atherosclerosis collagen synthesis predominantly involves synthetic GABA phenotype, while at progressing stages fibroblasts are predominantly involved. PMID- 3337893 TI - [The surfactant system and structure of the respiratory portion of the lungs during de-adaptation following a single exposure to acute pressure chamber hypoxia]. AB - The effect of acute pressure chamber hypoxia on the surfactant system and respiratory segment structure of the lungs were studied in rats by physical, fluorescent microscopic and morphometric methods. Acute hypoxia decreases surface activity, induces changes in cellular and extracellular surfactant fluorescence and causes the development of diffuse vesicular emphysema. On the first day of adaptation atelectatic foci dominate over emphysema, and the pulmonary structure normalizes afterwards. During de-adaptation, surface activity and cellular surfactant fluorescence are higher than the control levels. Surface activity and extracellular surfactant fluorescence recover steadily by the fifth day of adaptation. The amount of phagocytized surfactant in alveolar macrophages is increased, with the changes being opposite to those characteristic of extracellular surfactant. PMID- 3337894 TI - [Morphological changes in pulmonary alveolus macrophages as affected by alcohol and nitrosodimethylamine]. AB - Comparative electron microscopic studies of lung alveolar macrophage (LAM) ultrastructure (with their surface architectonics) were performed in transmission and scan regimen in 3 groups of animals: in intact rats and in rats 12 and 24 hours after a single intragastric administration of nitrosodimethylamine at a concentration of 30 mg/kg in one case and of 50% ethanol (2 ml per 100 g animal weight) in the other case. The transformation of cytoplasmic excrescences, manifested in their diminution, twisting and fusion resulted in the formation of fold-hilly LAM surface. The data obtained may be used for the elaboration of criteria for the assessment of environmental effects of toxic factors. PMID- 3337895 TI - Circulating glycosaminoglycan anticoagulants associated with suramin treatment. AB - A complex coagulopathy appeared in three women receiving suramin as treatment for metastatic adrenocortical carcinoma. Although hepatocellular dysfunction accounted for some of the abnormality, a unique feature of the coagulopathy was the presence of an inhibitor of the thrombin clotting time. The potency of this circulating anticoagulant increased markedly during exacerbations of hepatic injury. The anticoagulant was removed from plasma samples from two of the patients by passage over a column of diethylaminoethyl (DEAE)-Sephacel. It eluted from the DEAE at salt concentrations that removed "high-charge" glycosaminoglycans. Elimination of the purified anticoagulant activity in vitro required a combination of heparitinase and chondroitinase ABC, suggesting that the activity was mediated by both heparan sulfate and dermatan sulfate. Suramin is hypothesized to inhibit enzymes that normally degrade glycosaminoglycans, resulting in accumulation of these substances, which are released from the liver into the circulation during periods of hepatic injury. PMID- 3337896 TI - Restriction of cell lysis by homologous complement: I. An analysis of membrane attack complex formation on target membranes. AB - The hemolytic efficiency and binding of C9 to homologous and heterologous erythrocytes was evaluated by using a standardized passive sensitization procedure to prepare antigen- and antibody-coated erythrocytes (EA) and human serum for lysis. Heterologous bovine EA were readily lysed by human serum, whereas human EA were quite resistant to lysis. Human EA bound as many C8 and C9 molecules per cell as bovine EA when incubated under identical conditions, but four times as much bound C9 was required to lyse an equal number of human EA compared with bovine EA. The susceptibility of human erythrocytes did not increase when increased volumes of undiluted human serum were used although C9 binding increased to as much as 100,000 molecules per cell. Sodium dodecyl sulfate-resistant polymerized C9 (poly(C9)) was detected on both lysed ghosts and unlysed EA bearing complement proteins C1 through C9 (EAC1-9) after incubation with undiluted human serum; however, the ratio of poly(C9) to monomeric C9 was higher on unlysed cells than on ghosts. Although bovine and human EA bound equal amounts of human C9 at the end point, the rate of lysis and C9 uptake was slower on homologous cells. The rate-limiting step occurred before C9 binding and lysis because the rates of lysis and C9 binding were equal on homologous and heterologous EAC1-8 targets, but the extent of lysis of homologous cells was still lower than lysis of heterologous cells. Human erythrocytes lose restriction against homologous hemolysis during storage in autologous plasma or in isotonic buffers. PMID- 3337897 TI - Restriction of cell lysis by homologous complement: II. Protection of erythrocytes against lysis by newly activated complement. AB - Our previous work revealed that homologous complement (C) was ineffective in lysing antibody-sensitized erythrocytes (EA) even at high concentrations. It was also shown that activation of complement on homologous EA resulted in the binding of C9 and the formation of EA bearing complement proteins C1 through C9 (EAC1-9), yet few hemolytic sites were formed. Instead, as shown here, the formation of homologous EAC1-9 caused the cells to become resistant to lysis even by heterologous complement during a second incubation. In contrast, when homologous EAC1-8 were produced by incubating EA with C9-depleted serum, such intermediates were not protected against lysis by heterologous complement during a second incubation. Furthermore, homologous C9 on EAC1-9 was able to reduce the hemolytic efficiency of heterologous complement without blocking C activation and the formation of new C5b-9 complexes. Protection was not modified when homologous EAC1-9 were produced in one step, by incubation of EA with serum, or sequentially by adding C9 to EAC1-8. The minimum number of 9-sites required to confer a protective effect on EAC1-9 was less than 200 per cell. Thus, in addition to its known effect in heterologous cell killing, homologous C9 is capable of protecting homologous cells against inadvertent complement lysis. PMID- 3337898 TI - Platelet-agglutinating protein P37 from a thrombotic thrombocytopenic purpura plasma forms a complex with human immunoglobulin G. AB - We have previously reported the purification of a 37-kd platelet-agglutinating protein (PAP p37) from the plasma of a patient with thrombotic thrombocytopenic purpura (TTP) that was shown to be present in a subset of TTP patients. The platelet agglutination induced by PAP p37 has been shown to be inhibited by IgG from normal human adults and the same TTP patient after recovery. To elucidate the mechanism of inhibition of IgG, the interaction between PAP p37 and IgG was studied. The complex formation was demonstrated by the binding of fluid-phase IgG from normal adults and the same TTP patient after recovery to adsorbed PAP by using an enzyme-linked immunosorbent assay. The binding was specific, concentration dependent, and saturable. IgG purified from a 5-month-old baby and the same TTP patient during active disease did not form complex with PAP p37. The IgG covalently cross-linked to Sepharose 4B bound 125I-PAP p37 but not 125I fibrinogen. Sucrose density gradient ultracentrifugation of a mixture of 125I-PAP p37 and IgG also revealed the fluid-phase complex formation with a sedimentation value of 19S. Complexes of molecular weight ranging from 180,000 to over 350,000 daltons were also detected by molecular sieve chromatography. The IgG that was bound to PAP p37 conjugated to Sepharose 4B inhibited the agglutination of washed platelets induced by TTP plasma containing PAP p37, whereas the IgG that was not bound to PAP p37 did not have a significant inhibitory effect. The complex formation between PAP p37 and specific IgG is likely to account for the in vitro inhibition of TTP plasma-induced agglutination and, at least partly, the in vivo successful treatment with specific IgG-containing normal plasma. PMID- 3337899 TI - Natural history of idiopathic refractory sideroblastic anemia. AB - We analyzed the natural history of idiopathic refractory sideroblastic anemia (IRSA) in 37 patients studied between 1969 and 1986. Although erythroid abnormalities were prominent in all, 12 patients also showed involvement of the granulocytic and/or megakaryocytic cell lines, and nonrandom chromosomal aberrations were observed in five of 23 patients studied for such defects. Measurements of erythroid marrow function showed in most cases erythroid expansion with ineffective erythropoiesis. In seven patients, however, the erythroid activity was found to be inappropriately low for the degree of anemia. Transfusion dependence occurred in 26 of 37 cases. Iron overload was a common feature at presentation but produced clinical manifestations of hemochromatosis only in those patients who subsequently had a regular need for blood transfusions. Five patients progressed to bone marrow failure, and another five patients (two of whom had monosomy 7) evolved into acute nonlymphocytic leukemia (ANLL). The median survival was 72 months, with a high transfusion requirement, multilineage defects, and inappropriately low erythroid proliferation being associated with a poor prognosis. The most common causes of death were complications of iron overload and evolution into ANLL. We conclude that (a) the natural history of IRSA is characterized by an initial phase of erythroid hyperplasia and ineffective erythropoiesis, which is usually stable for many years but in a subset of patients may be followed by a phase of marrow failure with or without the later emergence of leukemic blasts; (b) peripheral blood counts, measurement of erythroid marrow function, and chromosomal analysis are useful for identifying subjects at risk of evolution into marrow failure or ANLL; and (c) IRSA patients with no need for blood transfusions are very likely to be long survivors, whereas those who become transfusion dependent are at risk of death from the complications of secondary hemochromatosis. PMID- 3337901 TI - Lineage- and stage-specific adhesion of human hematopoietic progenitor cells to extracellular matrices from marrow fibroblasts. AB - Local regulation of hematopoietic differentiation in the marrow requires close interactions with components of the microenvironment. In this study, we explored the capacity of human marrow hematopoietic progenitor cells to adhere in vitro to the extracellular matrix (ECM) secreted by human marrow fibroblasts. When marrow mononuclear cells were incubated on ECM-coated dishes, all types of progenitors adhered to this substrate through an active process requiring divalent cations and serum factors. The proportion of erythropoietic progenitors attached to ECM in two hours was at least twofold higher than that of granulopoietic progenitors. Moreover, in the erythroid lineage, the capacity to adhere to ECM increased with the degree of differentiation of the progenitor: 28% of CFU-E adhered to ECM as compared with 13% of immature BFU-E. Thus, ECM-mediated adherence varied both with the cell lineage and the maturation stage of the progenitor. Purified fibronectin could substitute for ECM in the adhesion assay, and ECM-mediated adhesion of CFU-E and BFU-E was partially inhibited by a polyclonal antifibronectin antibody, which implies that fibronectin may be one ECM component involved in progenitor cell adhesion. Incomplete inhibition of progenitor adhesion to ECM by the antifibronectin antibody, however, as well as the lower proportion of precursors attaching to purified fibronectin as compared with ECM suggest that other matrix molecules may also mediate erythroid progenitors attachment to ECM. These observations support the idea that hematopoietic progenitor cells may regulate their differentiation in part through the modulation of adhesive interactions with a number of constituents of the microenvironment. PMID- 3337900 TI - The polyadenylation site mutation in the alpha-globin gene cluster. AB - In a previous study, we described a form of nondeletion alpha-thalassemia (alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of alpha T Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in the polyadenylation signal of the alpha 2 gene and that the frameshift mutation in codon 14 of the linked alpha 1 gene is the result of a cloning artefact. The alpha 2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the alpha T Saudi alpha defect. PMID- 3337902 TI - Protein C deficiency resulting from possible double heterozygosity and its response to danazol. AB - A unique family with protein C (PC) deficiency is described. The proband had a history of renal vein thrombosis as a newborn and iliofemoral thrombosis at the age of 6 years. After 6 months of heparin treatment, discontinuation of anticoagulation therapy was accompanied by persistent hypofibrinogenemia with increased fibrinogen consumption. With continuous infusion of heparin, fibrinogen turnover normalized, and the child has remained free of thrombosis. Both the immunologic level of PC and the functional activity measured by amidolytic assay were moderately reduced (47% and 34%, respectively). Functional activity of PC measured by its anticoagulant activity was disproportionately lower (14%). A 3 year-old asymptomatic sibling had a similar disproportionate reduction of PC anticoagulant activity compared with the amidolytic activity or immunologic level. The mother demonstrated type I PC deficiency with a proportionate reduction in immunologic protein levels (59%), anticoagulant activity (52%), and amidolytic activity (46%), whereas the father had type II PC deficiency with normal immunologic protein levels (102%), normal amidolytic function (98%), but a low anticoagulant function (50%). An abnormal PC molecule was detected by two dimensional immunoelectrophoresis in the father and two children. These data are consistent with the hypothesis that the children are doubly heterozygous for two different types of PC deficiency inherited from each of the parents. A 14-day trial of danazol in the proband resulted in a rise in the PC antigen concentration from 66% to 98% but no change in PC anticoagulant function. PMID- 3337903 TI - Clinical factors influencing the efficacy of pooled platelet transfusions. AB - To determine the relative importance of clinical factors on the efficacy of platelet transfusions, 941 pooled platelet transfusions from HLA-unmatched donors were studied prospectively in 133 patients with bone marrow failure. Multiple linear regression analyses identified the major factors influencing one-hour corrected increments (CI) as prior splenectomy, bone marrow transplantation, disseminated intravascular coagulation, concurrent intravenous amphotericin B, splenomegaly, and HLA antibody grade. The relative impact of these factors on CI has been quantitated by using a formula developed from these data. A linear relationship was demonstrated between increasing percentage of HLA antibody grade and decreasing CI. A number of other factors were less important in the linear regression model than the aforementioned major factors. These included platelet specific antibodies, concurrent antibacterial antibiotics, clinical bleeding grade, and temperature. Factors that did not influence CI included the number of prior platelet transfusions, prior granulocyte transfusions, prior red cell transfusions, infection, age, blood group, diagnosis, sex, pretransfusion platelet count, prior pregnancies, and concurrent antineoplastic drugs. This study identified major clinical factors that significantly influenced CI and were major causes of refractoriness to pooled platelet transfusions. PMID- 3337904 TI - Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities. AB - Cytogenetic studies of 68 patients who developed secondary leukemia (SL)/dysmyelopoietic syndrome (DMS) after extensive chemotherapy and/or radiation therapy as well as patients who developed SL/DMS without such treatment showed that those patients who received radiation alone or with chemotherapy had more extensive numerical and structural abnormalities than those who received only chemotherapy. In terms of the specific chromosomal abnormalities, there are no differences between the various treatment groups. Hypodiploidy is the most common form of aneuploidy in these patients, with the most common numerical abnormality being the loss of chromosome 7. The most common structural abnormalities involved chromosomes 3 and 5. When compared with patients with de novo leukemia and DMS, the chromosomal abnormalities in these patients are more complex and extensive. Serial studies revealed that cytogenetic abnormalities do not precede the development of hematologic changes by significant time periods. PMID- 3337905 TI - Genetically determined polymorphism of the circulating human breast cancer associated DF3 antigen. AB - The murine monoclonal antibody (MAb) DF3 was prepared against a human breast carcinoma. Previous studies have demonstrated that DF3 antigen levels are elevated in plasma of patients with breast cancer. Furthermore, MAb DF3 reacts with circulating glycoproteins of different molecular weights ranging from approximately 300 to 450 kd. The present study demonstrates that plasma DF3 antigen is comprised of at least four moieties with slow (S), intermediate (I), rapid (R) and very rapid (VR) electrophoretic mobilities. The electrophoretic mobility patterns for circulating DF3 antigen differ among individuals. Moreover, DF3 antigen is detectable in urine, and the electrophoretic mobility of the urinary moieties is similar, but not identical, to that in the plasma. Studies in family members suggest that the electrophoretic heterogeneity of plasma DF3 antigen is determined by codominant expression of multiple alleles at a single locus. This locus may code for the core protein of DF3 antigen. These findings thus identify a genetically determined polymorphism of a circulating tumor associated glycoprotein. PMID- 3337906 TI - The effect of the plasticizer di-2-ethylhexyl phthalate on the survival of stored RBCs. AB - Recent in vitro studies have shown that di-2-ethylhexyl-phthalate (DEHP) inhibits the deterioration of RBCs during refrigerated storage in containers that use this compound as a plasticizer. The experiments described in this report were designed to assess whether this in vitro protective effect of DEHP would result in a prolonged in vivo survival of RBCs infused into normal human recipients. Whole blood collected from ten normal donors was stored for 35 days in citrate phosphate-dextrose-adenine (CPDA-1) anticoagulant contained in polyvinylchloride (PVC) bags plasticized with DEHP or a trimellitate compound that is known to have low leachability. Aliquots of RBCs from each container were then labeled with chromium-51 and were reinfused into the original donors. For blood stored in DEHP plasticized PVC bags, 24% more red cells survived in vivo 24 hours after reinfusion than was observed when the blood had been stored in trimellitate plasticized bags (P less than .001). Whole blood stored in glass bottles showed a similar improvement in in vivo survival when DEHP was added in weekly increments to mimic the accumulation of this plasticizer seen during storage in plastic containers. Survival of packed red cells stored in the presence of DEHP increased by 14% compared with storage in trimellitate-plasticized bags (P less than .05). In agreement with previous studies, hemolysis and microvesicle formation were also reduced in the presence of DEHP. These results suggest that proposed new storage systems lacking DEHP should be carefully evaluated to determine whether adequate post-transfusion survival of RBCs may be achieved. PMID- 3337907 TI - Plasma cell karyotype in multiple myeloma. AB - Karyotypic abnormalities were studied in multiple myeloma and were correlated with clinical features. Among 115 evaluable patients, 46% had an abnormal karyotype. Trisomy 3, 5, 9, and 15 and monosomy 13 and 16 were the most common clonal abnormalities. Translocations described previously in other B cell malignancies occurred in nine patients, including four with t(8;14)(q24;q32) translocations. The association of all t(8;14) abnormalities with IgA protein type suggested a pathogenetic relationship between a specific karyotypic abnormality and myeloma protein type. Hypodiploidy occurred mainly in patients with only Bence Jones protein, was associated with resistance to therapy, and justified the early consideration of investigational therapies. PMID- 3337908 TI - An apparently higher molecular weight gamma-chain variant in a new congenital abnormal fibrinogen Tochigi characterized by the replacement of gamma arginine 275 by cysteine. AB - A gamma-chain variant with an apparently higher molecular weight than the normal gamma-chain was detected in a new congenital abnormal fibrinogen with impaired polymerization of the fibrin monomer and with normal release of fibrinopeptides A and B in a 51-year-old male. Purified fibrinogen analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under the reduced condition in the system of Laemmli contained two protein bands in the gamma-chain region (molecular weight, 50,500 as compared with 50,000 for the normal), both with normal crosslinking ability. The presence of two types of gamma-chains was more clearly detected when reduced and carboxymethylated fibrinogen was analyzed by SDS-PAGE or when reduced fragment D2 was analyzed on SDS-PAGE followed by Western blotting, and identified by positive staining for anti gamma-chain monoclonal antibody. Cyanogen bromide- or lysylendopeptidase-cleavage of purified gamma chains analyzed on reverse-phase high performance liquid chromatography showed the decrease of one peptide compared with the normal and the appearance of an abnormal peptide peak. Amino acid sequence analysis demonstrated that the gamma arginine-275 of gamma-chain variant was replaced by a cysteine. These data suggest that some regions or conformations containing gamma 275 will affect the polymerization of fibrin monomers. The propositus' two daughters had the same abnormal fibrinogen. This unique inherited abnormal fibrinogen was designated as fibrinogen Tochigi, and the gamma-chain variant as gamma Tochigi. PMID- 3337909 TI - Evidence for posttranslational control of Hb C synthesis in an individual with Hb C trait and alpha-thalassemia. AB - The level of Hb C in the erythrocytes of individuals with Hb C trait decreases significantly in the presence of coexisting alpha-thalassemia. This relationship may result from the higher affinity of beta A than beta C for limiting amounts of alpha-globin during hemoglobin assembly. This mechanism would predict that the beta A and beta C synthetic capacity in alpha-thalassemic individuals with Hb C trait should be balanced despite the low levels of Hb C in their circulating erythrocytes. To directly test this prediction, we have measured the beta A and beta C synthetic capacity of reticulocyte RNA isolated from two individuals with Hb C trait, one with a normal alpha-globin genotype and one with alpha thalassemia. The balanced expression of beta A and beta C in both cases supports the proposed posttranslational control over Hb C expression. PMID- 3337910 TI - Detection of carriers of the autosomal form of chronic granulomatous disease. AB - The NADPH:O2 oxidoreductase catalyzing the respiratory burst in activated phagocytes from healthy individuals is not operative in phagocytes from patients with chronic granulomatous disease (CGD). In a microscopic slide test using the dye nitroblue tetrazolium (NBT), carriers of X-linked CGD can be recognized by a mosaic pattern of NBT-positive and NBT-negative cells, governed by the expression of an unaffected or an affected X chromosome, respectively. Until now, it has not been possible to detect carriers of the autosomal form of CGD (other than by family studies) because all cells of these carriers stain positive in the NBT test. We have investigated whether neutrophils from carriers of autosomal CGD can be recognized by measurement of the rate of oxygen uptake upon stimulation of the cells. It was found that with the phorbol ester PMA as a stimulus, the respiratory burst is significantly lower in autosomal CGD carriers. With serum treated zymosan as a stimulus, no difference between controls and carriers was observed. The addition of f-Met-Leu-Phe (1 microM) to PMA-activated neutrophils of control donors caused a transient increase in oxygen consumption of about 40%. Under these conditions, an increase of more than 100% was observed in neutrophils from carriers of autosomal CGD. These findings provide a simple method for the detection of carriers of the autosomal form of CGD. PMID- 3337911 TI - Spectrin Tunis (alpha I/78): a new alpha I variant that causes asymptomatic hereditary elliptocytosis in the heterozygous state. AB - Spectrin Tunis (alpha 1/78) was found in the heterozygous state in a young white North-African man and his mother. Both of them presented with mild elliptocytosis. Using one-dimensional electrophoresis, a sharp 78 kd fragment was present with a reciprocal decrease of the alpha I 80 kd domain. Kinetic analysis unambiguously confirmed that the 78 kd fragment developed at the expense of the alpha I 80 domain. The alpha I 74 kd peptide was not flanked with a peptide lacking a 2 kd fragment. From this fact, it could be inferred that the site for additional proteolysis is located upstream from arginyl residue 39 and, more precisely, should lie 10 to 20 amino-acid residues (-2 kd) from the alpha-chain N terminus. The percentage of spectrin dimers in 4 degrees C extracts was high (over 40%), contrasting with the absence of clinical symptoms related to elliptocytosis. This is the first mutation responsible for elliptocytosis found in Tunisia. PMID- 3337912 TI - Decreased erythrocyte nicotinamide adenine dinucleotide redox potential and abnormal pyridine nucleotide content in sickle cell disease. AB - RBCs from individuals with sickle cell disease are more susceptible to oxidant damage. Because key antioxidant defense reactions are linked to the pyridine nucleotides nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), we tested the hypothesis that the RBC redox potential as manifested by the NADH/[NAD+ + NADH] and NADPH/[NADP+ + NADPH] ratios is decreased in sickle erythrocytes. Our data demonstrate that sickle RBCs have a significant decrease in the NADH/[NAD+ + NADH] ratio compared with normal RBCs (P less than .00005). Interestingly, sickle RBCs also had a significant increase in total NAD content compared with normal RBCs (P less than .00005). In contrast, although sickle RBCs had a significant increase in the total NADP content compared with normal RBCs (P less than .00005), sickle RBCs had no significant alteration in the NADPH/[NADP+ + NADPH] ratio. High reticulocyte controls demonstrated that these changes were not related to cell age. Thus, sickle RBCs have a decrease in NAD redox potential that may be a reflection of their increased oxidant sensitivity. The changes in these pyridine nucleotides may have further metabolic consequences for the sickle erythrocyte. PMID- 3337913 TI - Protein co-isolated with human tissue factor impairs recovery of activity. AB - Preparations of human tissue factor isolated by immunoaffinity chromatography contain variable amounts of 47,000 mol wt, 55,000 mol wt, and multimeric tissue factor when analyzed without reduction on polyacrylamide gels in sodium dodecyl sulfate (SDS). When analyzed after reduction, the 47,000 mol wt tissue factor apoprotein and a protein of about 12,000 mol wt are observed. Elution of tissue factor from polyacrylamide gel slices, followed by reassociation with lipids, restored proportionately much greater tissue factor activity with the 47,000-mol wt protein than with the 55,000-mol wt form. Cyanogen bromide cleavage at the single tissue factor methionine revealed that the 12,000-mol wt protein is associated with the carboxyl-terminal peptide derived from the 47,000-mol wt protein. These results reveal that association of the 12,000-mol wt protein with the cytoplasmic domain of tissue factor can modulate its activity in vitro. PMID- 3337915 TI - Cell cycle characteristics in acute nonlymphocytic leukemia. PMID- 3337914 TI - Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. AB - In situ hybridization was used to localize the cells that produce erythropoietin (EP) in anemic murine kidneys. Kidneys from anemic and nonanemic mice were fixed and processed for paraffin embedding. Sections were hybridized with a 35S-labeled RNA probe complementary to mRNA coding for EP. An uncommon, but specific type of cell was intensely labeled in the cortices of anemic kidneys. The labeled cells were clearly nonglomerular and nontubular. Their location outside of the tubular basement membrane was consistent with that of a subset of interstitial cells or capillary endothelial cells. PMID- 3337917 TI - Fatal legionellosis in patients with malignant hematologic diseases. AB - Pneumonia was present in 70/157 (44.6%) autopsied patients with malignant hematologic diseases. In 16/70 patients (22.9%), legionellae were found to be the causative agents by screening lung tissue specimens with the direct fluorescent antibody method. In 5/16 patients with Legionella pneumonia, in whom legionellosis had been suspected clinically, the diagnosis had already been established by serology, urinary Legionella antigen detection, and culture. These results provide evidence that legionellosis is an important pneumonia etiology in patients with malignant hematological diseases. Thus, Legionella diagnostics should be applied routinely, and antibiotics effective in the treatment of legionellosis should be added to the usual therapy in patients with etiologically unexplained pneumonias. In view of the common occurrence of relapses of Legionella pneumonia, antibiotic therapy should be continued for an extended period. PMID- 3337916 TI - Sex-related differences in hematological values. A study on the erythrocyte and granulocyte count, plasma iron and iron-binding proteins in human transsexuals on contrasexual hormone therapy. AB - Hematological data known or supposed to be influenced by individual sex hormones were evaluated in 18 untreated transsexuals (TS) and in 20 castrated or non castrated TS on androgen and estrogen treatment, respectively. Profiting from a situation of clinically controlled hormonal sex-transformation it was tested, whether the circulating erythrocyte and granulocyte mass and iron metabolism are linked to a male and female sex-hormone constellation. The erythrocyte and granulocyte counts were significantly higher in untreated males and treated female-to-male TS than in untreated females and treated male-to-female TS. The unexpected finding of sex hormone-dependent granulocyte fluctuations was corroborated by parallel concentration changes of lactoferrin, a granulocyte derived plasma protein. Iron metabolism as judged from plasma iron, total iron binding capacity and serum ferritin was unaffected by sexual transformation. Plasma iron and the total iron-binding capacity did not differ significantly in untreated and treated TS of either type. The serum ferritin concentration, however, was significantly lower in untreated as well as in virilized females than in untreated and in feminized males, but was not significantly changed by long-term androgen or estrogen treatment. The present study demonstrates the potential of human transsexualism as a model for the study of sex-related biological processes. PMID- 3337918 TI - Leucostasis, an underestimated cause of death in leukaemia. AB - Massive sludging of leukaemic cells in blood vessels is a frequent and often lethal complication of leukaemia. In a retrospective clinicopathological study on the causes of death in 52 patients with acute myeloid leukaemia and myeloproliferative disease, pulmonary leucostasis was found in 40% of the patients. In many of these patients the vessels of the heart, brain and testes were also involved. In search for signs and symptoms specific for leucostasis, the clinical records of the 21 patients with leucostasis (the study group) were compared to those of 20 patients without leucostasis (the control group). Dysfunction of the organs most affected by leucostasis, namely lungs, heart and brain, was found more often in the study group than in the controls, but the combination of unexplained fever with cardiopulmonary and/or central nervous system failure occurred almost exclusively and in half of the patients with leucostasis. Leucostasis occurs predominantly, but not exclusively, in patients with high leucocyte counts, and especially, but again not exclusively, when the leucocyte counts rise sharply. PMID- 3337919 TI - Haemolytic anaemia as initial manifestation of Wilson's disease. AB - Common manifestations of Wilson's disease are disorders of the liver and brain. A rare complication of this inherited disease is acute intravascular haemolytic anaemia. We report the case of a 33-year old female patient who was admitted to the hospital with acute haemolysis as the initial symptom of Wilson's disease. The haemolysis preceded the definitive diagnosis by 20 months. It is concluded that in any case of unclear haemolytic anaemia, especially in adolescents or in young adults, Wilson's disease should be considered. PMID- 3337920 TI - The importance of a female therapist in a male Vietnam veterans' psychotherapy group. PMID- 3337922 TI - Surviving suicide. A journey to resolution. PMID- 3337921 TI - Developmental pathogenesis of narcissistic disorders in children. PMID- 3337924 TI - An obsessional variant of capgras symptom: a case report. PMID- 3337923 TI - Humiliation and shame. Comparing two affect states as indicators of narcissistic stress. PMID- 3337925 TI - The song of the leper: empathic communication with convicts. PMID- 3337926 TI - The aftermath of catastrophe: the Hyatt Regency disaster. PMID- 3337927 TI - Significant changes in Ritchie scores. AB - A study was designed to establish the reliability of assessing joint tenderness in rheumatoid arthritis. Reliability both within and between observers was measured and the 95% confidence intervals (CI) for a change in score calculated. Forty-two patients were assessed by two metrologists over a 14-week period using three subjects per week. Results showed close agreement within and between metrologists. The 95% CI for repeat measures by the same metrologist was +/- 8.5 and +/- 12 by a different metrologist. Taking a change of 5 in the score as clinically significant, the 95% CI for a clinically significant change would be +/- 14 with one observer and +/- 17 when a different observer repeated the assessment. It is recommended that other centres should establish their own CI for a change in scores when undertaking clinical trials. PMID- 3337928 TI - What are the 'best' measurements for monitoring patients during short-term second line therapy? AB - Seventy-one patients with active rheumatoid arthritis were treated with one of five second-line agents and monitored for 24 weeks using seven clinical and seven laboratory measurements. Statistical tests were used to determine which measures changed fastest, which changed most and which most closely reflected changes in the others. The results consistently showed that articular index and summated change score were the 'best' clinical measures while ESR and plasma viscosity were the 'best' laboratory measures. Traditional measures such as grip strength and joint size fared badly and cannot be recommended. Clinical variables improved slightly more rapidly than laboratory measures, but the latter showed the greater change. PMID- 3337929 TI - Naproxen dose and concentration: response relationship in rheumatoid arthritis. AB - Information on the relationship between the plasma concentration of nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical response in rheumatoid arthritis is sparse. As a result treatment is often relatively empirical. Standard doses are prescribed and an apparent lack of response leads either to the prescription of another drug, or an increase in the dose beyond that recommended. This study investigated 18 patients given three doses (500, 1000 and 1500 mg/day) of naproxen in a randomized double-blind design for 12 days at a time. Using a linear modelling approach we found that three out of four clinical response measurements improved linearly with increasing naproxen trough concentrations, suggesting that most patients will achieve an improvement in symptoms if the dose of naproxen is increased up to 1500 mg/day. However, since trough naproxen concentrations show a less than proportional increase with increasing dose (due to saturation of binding sites on plasma albumin), the improvement in response will be less dramatic as the dose is increased. PMID- 3337930 TI - Markers and subsets--clue to pathogenesis in systemic lupus erythematosus? PMID- 3337931 TI - District rheumatology services. A report by the Committee on Rheumatology of the Royal College of Physicians of London. AB - The Committee on Rheumatology was seriously concerned about variations in the availability of services for patients with rheumatic diseases in different parts of the country. It commissioned a draft report to document various aspects of the present situation which would then be augmented, on this basis, by proposals for the establishment of basic requirements and minimum standards for a district rheumatology service. The draft was considered and adopted, and the report has now been approved by the Royal College of Physicians of London; in its final form it is now an official College document. This paper sets out the contents of the report endorsed by the College Committee. PMID- 3337932 TI - Bilateral adhesive capsulitis, oligoarthritis and proximal myopathy as presentation of hypothyroidism. AB - A patient who presented with bilateral adhesive capsulitis of the shoulder, oligoarthropathy and rapidly progressive proximal myopathy is described. Although clinically euthyroid, autoimmune and biochemical hypothyroidism was the only predisposing factor found. Clinical deterioration after initiation of thyroxine replacement was followed by delayed improvement with reduction in initially elevated ESR and CRP. PMID- 3337935 TI - Hyperbaric oxygen treatment for rheumatoid arthritis; failure to show worthwhile benefit. PMID- 3337933 TI - Tuberculous arthritis of peripheral joints in patients with previous inflammatory rheumatic disease. AB - Four patients with a previous inflammatory rheumatic disease developed a peripheral tuberculous (TB) arthritis in a joint apparently affected by a rheumatic disease. The single most important factor in the diagnosis of TB was the presence of past or present pulmonary TB or a family history on a background of steroid use. Clinical presentation, disease evolution, and routine laboratory tests were unhelpful. The most effective method of diagnosis was synovial biopsy. PMID- 3337934 TI - Determinants of disability in rheumatoid arthritis. AB - The longitudinal determinants of disability were studied in a group of 30 patients with rheumatoid arthritis over a 3-year period. The patients were investigated on two occasions using quantitative measures of disease activity and disability as well as a series of reliable psychometric instruments. Both longitudinal and cross-sectional data analyses were performed. Psychological factors consistently predicted more of the variance of disability than disease activity. These factors were associated with the tendency to deny the emotional dilemmas caused by having a chronic illness, difficulty in accepting doctors' reassurances and clinical depression. Such psychological variables required specific attention in rehabilitation programmes. PMID- 3337936 TI - SLE in black S. Africans. PMID- 3337937 TI - Referrals from general practice to a rheumatology clinic. PMID- 3337938 TI - Has the incidence of rheumatoid arthritis declined in the United Kingdom? PMID- 3337939 TI - Magnetic resonance imaging in neuro-Behcet's disease. PMID- 3337941 TI - Results of resection of gastric cancer extending to adjacent organs. AB - We report the late results of resection in 281 patients with gastric carcinoma extending to adjacent organs. In 92 without incurable factors (peritoneal dissemination, liver metastasis and widespread nodal involvement) the 5-year survival rate was 36.7 per cent in those treated by gastrectomy and complete removal of the invaded organ. This value is significantly higher than the 17.4 per cent recorded in those undergoing gastrectomy alone or with incomplete removal of the invaded organs (P less than 0.05). In 189 patients with incurable factors, the 5-year survival rates were 5.4 and 2.8 per cent respectively in cases of complete and incomplete excisions. This tendency was similar in patients with a single invaded organ and also in those with plural organ involvement. In potentially curable patients treated by complete excision, the probability of long-term survival was statistically better than that following incomplete excision only when the pancreas was involved (P less than 0.05). We recommend complete excision of invaded organs, irrespective of the number or site of organs involved, provided that there is no evidence of incurable factors. PMID- 3337940 TI - Cervical myelopathy in rheumatoid arthritis: no relationship to surgery. PMID- 3337942 TI - Surgical management of bleeding gastric ulceration. AB - In a nine-year period from 1977 to 1985 sixty-one patients underwent surgery for bleeding gastric ulceration in the Western Infirmary, Glasgow. Nineteen patients were treated by partial gastrectomy, twenty-two had undersewing of the ulcer plus vagotomy and drainage and twenty had undersewing alone. Mortality in the three groups was 26, 45 and 10 per cent respectively. All groups of patients were similar in terms of age, severity of haemorrhage, delay before surgery and grade of surgeon performing the procedure. Out-patient follow-up (mean: 37 months) of patients treated by undersewing alone revealed that 73 per cent were symptom free. Treatment of bleeding gastric ulceration by undersewing alone is effective and should be considered in patients who require surgery. PMID- 3337943 TI - Growth rate of human tumour xenografts measured in nude mice by in vivo cast modelling. AB - Caliper measurement of xenograft tumour volume incurs shape-dependent errors of up to 230 per cent. A more sensitive and accurate method is described for repeated in vivo measurement of tumour volume by cast modelling. The technique can provide electronic data for further analysis and its accuracy and limitations can themselves be determined. Week-on-week changes in tumour volume may be detected with up to 99 per cent confidence. PMID- 3337944 TI - Improvements in the treatment and prognosis of colorectal carcinoma. AB - In a survey of the surgical results in 709 patients with colorectal carcinoma (CRC) treated between 1976 and 1985 a favourable shift of stage distribution was observed. The tumour was localized (Dukes' classification A or B) in 61 per cent of patients, as compared with 47 per cent in the previous 10-year period. This change was, in part, due to different interpretation of stage definitions. Clear improvements of the results were, however, also noted. Radical surgery was possible in 76 per cent of patients and the primary tumour was removed in 93 per cent. Surgical mortality was 4.4 per cent and complication rate 15 per cent, significantly less than earlier (6.5 and 38 per cent, respectively). Increasing numbers of sphincter-saving operations were performed in rectal cancers (47 per cent as compared with 24 per cent in the previous 10-year period). The overall 5 year survival rate improved from 40.5 to 52.5 per cent. Premalignant conditions were identified in 12.6 per cent of patients: previous CRC 4.8 per cent, cancer family syndrome 4.1 per cent, ulcerative colitis 1.7 per cent and familial adenomatosis 0.6 per cent. In order to sustain the favourable trend of improving survival prospects, more emphasis must be directed to the detection of early stage cancers. PMID- 3337945 TI - Prognostic significance of DNA ploidy in colorectal cancer: a prospective flow cytometric study. AB - A prospective study of prognostic factors has been carried out in a group of 123 consecutive patients with colorectal cancer. The fate of all patients is known at 3 years after operation. Clinical and pathological data were recorded at the time of presentation and operation, and the patients have been subject to regular postoperative review. DNA ploidy status was determined by flow cytometry. In all, 39 (33 per cent) patients had DNA diploid tumours and 80 (67 per cent) patients had DNA aneuploid tumours. In four cases, tumour material was not obtained. The patients with DNA aneuploid tumours had a worse prognosis than those with DNA diploid tumours, but this was only seen in those patients classified as Dukes' B. In a Cox's regression analysis, the surgeon's assessment of operability was the strongest predictor of survival, followed by the pathological classification and the patient's age. After these factors had been considered, the DNA ploidy status conferred no independent survival value. PMID- 3337946 TI - Penile incarceration by a metallic object. PMID- 3337947 TI - Complete rectal prolapse: the anatomical and functional results of treatment by an extended abdominal rectopexy. AB - Between 1970 and 1985 (inclusive), 66 patients presented with complete rectal prolapse; 59 (89 per cent) were treated by extended abdominal rectopexy. Forty four patients (75 per cent) have been followed for more than 2 years: all cases were cured of their complete prolapse, no patients died, and major complications were few. Constipation (47 per cent) and incontinence (19 per cent) caused serious problems for many patients postoperatively. PMID- 3337948 TI - Tubercular fistula in ano. AB - Of 122 patients with fistulae in ano operated upon in a 5-year period, 19 (15.6 per cent) were found to have tubercular fistulae on histopathological examination. There was no characteristic clinical picture and concomitant pulmonary tuberculosis was present in only three patients. Histological examination of the excised fistula is mandatory for the diagnosis of anal tuberculosis. There were no cases of Crohn's disease of the anal region. PMID- 3337949 TI - Assessment of microtransducers in anorectal manometry. AB - It has been reported that microtransducer-tipped catheters (transducer) produce reliable reproducible measurements which correlate well with water-filled balloon systems. Maximum resting pressure (MRP) and maximum voluntary contraction pressures (MVC) were compared using a standard station pull-through technique in 12 patients. There was a poor correlation for both MRP: microballoon, 115 cmH2O (60-160 cmH2O); transducer 60 (20-110), r = 0.62, P less than 0.05, and MVC: microballoon, 202 (60-375); transducer, 175 (60-210), r = 0.42, n.s. To determine whether this was due to radial variation in pressures measured by the transducer, we studied a further 39 patients with both systems. At each station, transducer measurements were made at each of four quadrants. We found better correlation for MRP: microballoon, 100 (40-175); transducer, 66 (34-120), r = 0.72, P less than 0.001, and MVC: microballoon, 225 (55-650); transducer, 180 (50-470), r = 0.87, P less than 0.001, but a significant radial variation for the transducer where rotation reduced MRP pressure measurements by 21 per cent (0-600 per cent), and MVC 17 per cent (0-76 per cent). Moreover there was a significant difference between anterior and posterior MRP in the upper anal canal, anterior 35 (5-80) versus posterior 25 (10-60), P less than 0.05. These results account for the poor correlation between random positioning of the microtransducer-tipped catheter and indicate that radial orientation must be taken into account. PMID- 3337950 TI - Anorectal sampling: a comparison of normal and incontinent patients. AB - It has been suggested that sampling of rectal contents by the anal canal may play a role in the continence mechanism. To investigate this concept we studied 18 patients with faecal incontinence and 18 age and sex matched controls. A microtransducer catheter was positioned so that pressures were recorded from the rectum, the junction of the upper and middle thirds of the anal canal and the lower anal canal. Recordings were taken at rest and while distending the rectum with air in a balloon, and then with air injected freely into the rectum. Sampling (equalization of the rectal and upper anal canal pressures) was seen to occur spontaneously in 16 of the controls and only 6 of the incontinent group (P less than 0.02) and induced sampling occurred at a higher rectal volume in the incontinent group than in controls for freely injected air (P less than 0.002). Defective anorectal sampling may be an important contributory factor in the pathogenesis of anorectal incontinence. PMID- 3337951 TI - Prospective study of the effects of postanal repair in neurogenic faecal incontinence. AB - The most important factor associated with a good result in the surgical treatment of neurogenic faecal incontinence by postanal repair is considered to be restoration of the obtuse anorectal angle. Sixteen patients (14F:2M; median age 59 years) with neurogenic faecal incontinence confirmed by a raised fibre density in the external anal sphincter underwent postanal repair. Pre- and postoperative manometric assessment was performed in 16 and radiological assessment in 12. Normal ranges for these parameters were established in age and sex matched control subjects. Continence was improved in 14 (88 per cent) patients, 6 (38 per cent) of whom regained normal continence, at a minimum of 15 months follow-up. A successful outcome was associated with no significant change in basal (pre operative 35 (10-85) cmH2O, postoperative 44 (12-105) cmH2O; n.s.) or voluntary (pre-operative 43 (5-150) cmH2O, postoperative 32 (12-180) cmH2O; n.s.) components of anal canal pressure. There was a small but significant increase in sphincter length (pre-operative 2 (0-3) cm, postoperative 2.5 (0-3.5) cm; P less than 0.01). There was no significant change in the anorectal angle at rest (pre operative 96 (90-110) degrees, postoperative 107 (79-118) degrees; n.s.) in the patients in whom continence was restored and five of these patients had resting anorectal angles within the normal range (75-94 degrees). Thus postanal repair need not be restricted to patients with widening of the anorectal angle since its beneficial effects do not appear to be related to reduction of this angle. PMID- 3337952 TI - Investigation of anorectal function. AB - Anorectal function tests were performed in 280 consecutive patients, who were referred for evaluation of different anorectal disorders. The relationship between the estimated anal sphincter pressure on digital palpation and the measured pressure on anal manometry was investigated and the interrelationship between anal manometry, rectal capacity and the saline infusion test was defined. A significant correlation (P less than 0.001) was found between digitally and manometrically measured anal sphincter pressure. Considering the relationship between the three specific anorectal function tests, only manometry and the saline infusion test correlated to some extent (P less than 0.01). This study shows that digital palpation is helpful in anorectal function investigation, but to establish the exact anal pressures, anal manometry is mandatory. Furthermore, the poor correlation observed indicates that single tests represent different aspects of anorectal function and therefore they need to be performed together. PMID- 3337954 TI - Prognosis after simple incision and drainage for a first-episode acute pilonidal abscess. AB - During a 3-year period 73 patients were treated consecutively for a first-episode acute pilonidal abscess with simple incision and drainage under local anaesthesia. In all cases the treatment relieved symptoms and all patients returned to work immediately after treatment. Healing per primam occurred in 42 patients (58 per cent; 95 per cent confidence limits: 45-69) within 10 weeks after treatment. These patients had significantly fewer pits and lateral tracts compared with patients who developed excessive granulation tissue after incision and who required definitive surgical treatment later. Nine patients (21 per cent; 95 per cent confidence limits: 10-37) with healing per primam developed recurrence of their pilonidal disease during the prospective follow-up period (median follow-up period was 60 months, range 36-84 months). Actuarial analysis of the data revealed a constant cure rate of 76 per cent (95 per cent confidence limits: 57-95) after 18 months. PMID- 3337953 TI - Anal fissure in Crohn's disease. AB - There is little information on the natural history of anal fissure in Crohn's disease. The case notes of all new patients with Crohn's disease attending one hospital between 1977 and 1983 were reviewed: there were 61 patients with this diagnosis and an unhealed anal fissure as the only anal lesion. Of these 61 patients the fissure healed in 42 (69 per cent) during medical treatment of the intestinal disease. Ten patients (16 per cent) developed other anal lesions and in the remaining nine patients the fissure remained unhealed at the time of rectal excision (six) or last out-patient attendance (three). Activity of the fissure did not reflect disease activity elsewhere in 11 cases in whom healing of the fissure occurred despite progressive intestinal disease subsequently requiring resection. This study validates the policy of conservative management of anal fissure in Crohn's disease with anal surgery (required in 9.8 per cent of patients in this series) being reserved for the development of other anal disease. PMID- 3337955 TI - Treatment of 'inoperable' neck nodes using surgical clearance and postoperative interstitial irradiation. AB - The inability to remove all disease at the time of a radical neck dissection, or inoperable recurrent disease after a neck dissection, are both familiar problems for the head and neck surgeon. All too frequently the conventional treatment options have already been used, the patient having received external beam radiotherapy and possibly cytotoxic chemotherapy. In such circumstances, and provided that the primary tumour remains under control, a positive approach to the further management of the neck metastases should be adopted, given that the patient is in otherwise reasonable health and does not have gross distant metastatic disease. We describe our experience with postoperative interstitial irradiation (brachytherapy) using after-loaded iridium-192 (192Ir) wires positioned at the site of the tumour after its surgical exposure and debulking or clearance. All the treated patients had previously received external beam irradiation to the neck and in the first three cases local skin necrosis occurred as a sequel to interstitial implantation. Therefore, in the other five patients, cutaneous or myocutaneous flaps were used to resurface the area at the time of implant placement. This combination of techniques, which has not been described previously, provided local tumour control in four out of the five cases without irradiation necrosis occurring in any of them. PMID- 3337956 TI - Use of myocutaneous flaps for primary cover following lymph node dissection for malignant melanoma. AB - We report seven patients undergoing palliative surgery for advanced malignant melanoma, who required wide excision of skin and underlying tissue in association with lymph node dissection. In each case, primary closure of the wound was facilitated by the use of a myocutaneous flap. Four ilio-inguinal lymph node dissections were closed with rectus abdominis flaps, two cervical dissections were closed with a pectoralis major flap, and a limited latissimus dorsi flap was used for one axillary clearance. Primary healing was achieved in all cases; morbidity was low, with one wound infection and two limited lymphatic collections. All donor sites were closed primarily and healed well. We conclude that in selected patients the use of a myocutaneous flap procedure gives excellent coverage of large defects with low morbidity. In particular, there is rapid convalescence and return of good function after palliative resections, while the wide excision minimizes local recurrence where the tumour is in proximity to overlying skin. PMID- 3337957 TI - Acral (volar-subungual) melanoma in Auckland, New Zealand. AB - We have retrospectively reviewed the charts of 34 acral melanoma patients (melanoma arising from the volar skin of the hands, feet or a subungual site) seen in the Auckland area between 1970 and 1985. These 34 patients constituted 3.5 per cent of the total number of patients (972) reviewed over this period. Six of the thirty-four patients were either Polynesian or Maori. There were 19 men and 15 women, and the mean age of the group was 59 years. The primary lesion arose from the plantar or palmar skin in 25 patients and 9 patients had subungual lesions. All lesions but one were pigmented. Most patients with plantar or palmar lesions presented with clinical stage 1, Clark's level 4 disease, while those with subungual lesions presented most commonly with stage 2, Clark's level 5 disease. Treatment was wide local resection for plantar and palmar lesions and amputation for subungual lesions. Regional lymph node dissection was performed in 10 patients with positive nodes at presentation and in 6 patients who developed metachronous nodal disease. Patients were followed for between 1 and 16 years, and 18 patients died in this period, 15 of metastatic melanoma (mean time 34 months). Subungual melanoma carried a worse prognosis than melanoma arising in palmar or plantar skin. PMID- 3337958 TI - Omental viability and incisional herniation after omental transposition for the repair of chest wall defects. PMID- 3337959 TI - Maximal isokinetic muscle strength in patients with primary hyperparathyroidism before and after parathyroid surgery. AB - Primary hyperparathyroidism (HPT) is associated with symptoms of generalized fatigue and muscle weakness. The purpose of this study was to investigate muscular function in HPT quantitatively and to evaluate the effect of parathyroid surgery in this respect. The maximal isokinetic muscle strength (peak torque) of knee extension and flexion was measured with a Cybex-II dynamometer in 16 patients with primary HPT (mean serum calcium 2.81 +/- 0.14 mmol/l), four of whom had subjective impairment of strength, and in nine control patients submitted to hemithyroidectomy due to atoxic thyroid adenoma. Before surgery there was no significant difference in muscle strength between the two groups, neither was there any consistent relationship between the subjective feeling of muscular weakness and the measured peak torque. Seven months after surgery the HPT patients had increased their muscle strength by 8 per cent (P less than 0.05). The improvement was correlated with the pre-operative serum calcium levels (r = 0.56, P = 0.02) and was particularly seen in patients with pre-operative subjective muscular weakness. Patients with only slightly raised calcium values and without subjective muscular symptoms did not benefit clearly from surgery, compared with the controls. The study demonstrates that HPT patients, especially those with neuromuscular symptoms, can improve their muscle strength after parathyroid surgery. PMID- 3337961 TI - Small bowel volvulus complicating intestinal ascariasis in children. AB - Twenty-nine patients in whom small bowel volvulus complicated intestinal ascariasis are reported. Attention is drawn to the varied clinical and radiological presentation and the relationship of volvulus to the use of vermifuge. The mortality of 17 per cent was contributed to by delay in diagnosis and failure of pre-operative resuscitation. Early diagnosis is dependent upon clinical vigilance and repeated radiological assessment of those patients with simple ascaris obstruction who fail to improve rapidly with conservative treatment. The instillation of intraluminal vermifuge intra-operatively has minimized postoperative worm migration through suture lines and anastomoses. PMID- 3337960 TI - Platelet aggregation on peritoneal tube grafts and double velour grafts in the inferior vena cava of the pig. AB - In 14 pigs the infrarenal vena cava was replaced with a peritoneal tube graft or a collagen-coated double velour graft. With 111In-labelled platelets dynamic in vivo imaging of platelet aggregation over the graft was carried out using a scintillation camera. After removal, the grafts were examined by autoradiography for an evaluation of the platelet aggregation pattern. Measurements of activity in different regions of the grafts were also performed. The results indicated low activity uptakes both in vivo and in vitro. The dynamic study did not show any uniform increase of activity content 1-3 h postoperatively, in any of the groups. During the period 2-3 h postoperatively no increasing activity accumulation was found. Hemashield Microvel grafts had an uptake of 0.19 per cent of the total activity while the corresponding figure for peritoneal tube grafts was 0.17 per cent. The activity distribution on different parts of the grafts indicated lower accumulation on the Hemashield graft surfaces than in the anastomoses, while the accumulation was higher on the graft surface of peritoneal tube grafts. The autoradiographical findings supported this indication. In conclusion, low platelet aggregation was found with both dynamic in vivo imaging and in vitro activity measurements on both peritoneal tube grafts and collagen-coated double velour grafts. PMID- 3337963 TI - Anastomotic recurrence in large bowel cancer. PMID- 3337962 TI - Pancreatic abscess: results of prolonged irrigation of the pancreatic bed after surgery. AB - The mortality from pancreatic abscess may approach 70 per cent and the survivors often require repeated operations to debride the pancreas and to drain recurrent abscesses. We report the results of prolonged irrigation of the pancreatic bed after surgical debridement in 11 patients. Surgery was performed at an average of 17 days (range 8-25 days) after the onset of symptoms. The pancreatic slough was thoroughly debrided and 2-6 large drains were placed in the pancreatic bed. Irrigation with saline or Diaflex solution (2-6 l/day) was started after 2 days and continued for a mean of 25 days (range 5-54 days). There were three deaths (27.3 per cent) after surgery: one of these patients required reoperation and packing for massive postoperative haemorrhage and all three had some evidence of persisting sepsis at autopsy. Prolonged irrigation of the pancreatic bed after surgical debridement may reduce mortality and the need for repeated drainage procedures in patients with pancreatic abscess, but the detection and treatment of persisting sepsis remains the major problem. PMID- 3337964 TI - Ascaris lumbricoides and intestinal perforation. PMID- 3337965 TI - Glasnost on pesticides. PMID- 3337966 TI - Epidural morphine for postoperative analgesia. PMID- 3337967 TI - Osteomyelitis due to Kingella kingae infection. AB - A case of osteomyelitis due to Kingella kingae is presented to illustrate the insidious onset and indolent course typical of bone infections caused by this organism. The frequently negative result obtained with Gram's stain and the fastidious nature of the organism makes diagnosis difficult. Initial therapy with an aminopenicillin such as ampicillin in addition to antimicrobial drugs for Staphylococcus aureus should be effective in resolving bone and joint infections in children. PMID- 3337969 TI - Heparin-induced thrombosis (white clot syndrome) secondary to prophylactic subcutaneous administration of heparin. AB - As a reminder that thrombocytopenia may occur even with very small doses of heparin, the author describes the case of a 76-year-old man who was admitted for elective hip surgery and received "mini-dose" heparin prophylactically. Profound thrombocytopenia developed, followed by deep vein thrombosis and then arterial occlusion to the lower limb. Initially, the importance of the low platelet count was not recognized and a continuous infusion of heparin (35,000 units/d) was given. It was discontinued when the limb became cold, pulseless, paralysed and anesthetic, and an emergency aortogram demonstrated occlusion of the femoral artery. Removal of the thrombus, closed fasciotomies, infusion of Rheomacrodex in dextrose and administration of warfarin resulted in the patient's recovery of sensation and movement in the limb. PMID- 3337968 TI - Bladder-outlet reconstruction in neurogenic bladder due to myelomeningocele. AB - In a subgroup of children with myelomeningocele, urinary incontinence cannot be managed by clean intermittent catheterization and anticholinergic medication. The authors report on 24 such children who required bladder-outlet reconstruction. Twelve boys underwent the Young-Dees/Leadbetter procedure, 8 girls underwent the Burch procedure and the remaining 4 had a combination of the two. Augmentation cystoplasty was also carried out in seven girls and one boy. Results were most favourable in the girls, with improvement in 92%, in contrast to the boys in whom only 58% were improved. Artificial sphincter placement may be a more beneficial alternative for boys. PMID- 3337970 TI - Pseudocalculus of the common bile duct. AB - Common-bile-duct growths are rarely identified unless they cause chronic biliary obstruction. This case report describes a 71-year-old woman who had jaundice and epigastric pain. A cholecysto-colonic fistula was demonstrated by endoscopic retrograde cholangiopancreatography. The patient also had multiple filling defects in the common bile duct. The fistula was closed and stones were removed. A postoperative cholangiogram showed two calculi. One was removed with a basket through the T-tube tract, but the second, which did not appear completely free of the common-duct wall, could not be removed by the basket method. Subsequently at laparotomy this was found to be a benign pedunculated polyp, composed of collagenous and vascular tissue and with no surface epithelium. Surgeons should bear in mind the possibility of a common-bile-duct growth in cases of extrahepatic biliary obstruction. PMID- 3337971 TI - Healing of extra-articular angulated apex volar fractures of the distal radius. AB - Healed extra-articular angulated apex volar fractures of the distal radius are a relatively common orthopedic finding. The functional end-results of treatment of this injury are controversial. Twenty-nine patients with 34 fractures were reviewed by subjective and objective assessment, as well as radiologic examination. Some had unsatisfactory results. These poor results were associated with older age, poor anatomical reduction and, in some, the presence of a midcarpal instability pattern. PMID- 3337972 TI - Giant-cell tumour of the sacrum in a child. AB - Giant-cell tumours rarely are seen in children before epiphyseal fusion occurs and such tumours in the spine are uncommon. The authors report the case of a giant-cell tumour of the sacrum that developed in a 12-year-old girl before epiphyseal fusion. Embolization with activated microfibrillar collagen relieved her symptoms and was carried out twice before progression of the tumour necessitated radiotherapy. Giant-cell tumours of the spine are particularly difficult to manage since the accepted treatment for such tumours at other sites is wide resection, excisional curettage or surgical curettage with chemical cautery. However, embolization alone or combined with other methods of treatment is valuable, particularly in non-resectable giant-cell tumours of the spine. PMID- 3337973 TI - Retroperitoneal perforation of the rectum during barium enema examination. AB - Colorectal perforation during barium enema examination is rare. The authors report the case of an 84-year-old woman in whom retroperitoneal perforation of the rectum occurred during barium enema examination. Potential mechanisms of injury include trauma, overinflation of the balloon, recent instrumentation and associated disease of the rectal mucosa. When the colon has been well prepared before examination, and air alone, not barium, has been insufflated into the retroperitoneum, then such injuries may be managed successfully without operation, as in this case. PMID- 3337974 TI - Tuberculous enteritis and peritonitis. AB - In Turkey, diseases associated with Mycobacterium tuberculosis are common. Intestinal tuberculosis has generally been a complication of pulmonary tuberculosis, but recently there has been an increase in the frequency of intestinal tuberculosis without the pulmonary form. The authors present their experience over 8 years in 41 patients (aged 15 to 56 years) who underwent surgery for tuberculous enteritis (14), peritonitis (13), a combination of the two (5), genital tuberculosis and peritonitis (5) and tuberculous mesenteric lymphadenitis (4). Of these, 29 had no associated pulmonary tuberculosis. Eighteen of the 41 patients had complications of their disease-bowel obstruction in 13, intestinal perforation in 2, intestinal bleeding in 2 and enterocutaneous fistula in 1. The diagnosis was established at operation and by the appearance of caseating granuloma on histologic examination and isolation of the causative organism. Twenty-four patients required emergency surgery; 2 who had bowel perforation died. Operative procedures included laparotomy with biopsy (17), resection of intestine (10), division of adhesions (7), evacuation of mesenteric abscesses (4) and bypass (3). There were seven (17%) operative deaths. The authors recommend that noninvasive procedures be used for the diagnosis of intestinal tuberculosis, but if these fail, surgery is indicated. PMID- 3337975 TI - Effect of various low-dose concentrations of verapamil cardioplegia on small amplitude electrical activity during cardioplegic arrest. AB - The effect of verapamil cardioplegia on atrioventricular conduction was examined in 19 dogs. During 90 minutes of ischemic arrest, five dogs received multidose potassium cardioplegia, containing 1.2 mg/L of verapamil (group 1), five received potassium cardioplegia containing 600 micrograms/L of verapamil (group 2) and nine animals received cardioplegia containing 300 micrograms/L of verapamil (group 3). Atrioventricular conduction was measured in all groups before bypass, after 90 minutes of ischemia and after 45 minutes of reperfusion. Specially designed plunge electrodes were used to monitor the electrical status of the heart during arrest in group 3 and, in addition, left ventricular function and concentration of high-energy phosphates were determined before and after ischemic arrest. Conduction was prolonged in four group 1 dogs and in two group 2. Atrioventricular conduction was measured in six group 3 dogs; five had prolonged conduction and one experienced second-degree heart block. Small-amplitude electrical potentials were recorded from the myocardium in two of nine dogs in group 3. Persistent electrical activity was associated with continued use of high energy phosphates and resulted in decreased left ventricular function after 90 minutes of ischemic arrest. Our data indicate that small doses of verapamil will delay atrioventricular conduction and will not prevent small-amplitude electrical activity. PMID- 3337976 TI - [Compartment syndrome of the legs and scurvy]. AB - Old people living alone and in poverty are most at risk for developing scurvy, but the diagnosis may be missed unless the physician is aware of it. A 42-year old immigrant living in poverty was treated surgically at the Hotel-Dieu Hospital in Montreal for a compartment syndrome of the leg. She had ecchymoses on the skin of the leg and an interstitial hematoma in both posterior compartments. Three weeks later, she was readmitted with more swelling in the leg, gingivitis, hemorrhagic folliculitis, petechiae and gastrointestinal hemorrhage. Her response to vitamin C was remarkable and confirmed the diagnosis of scurvy. PMID- 3337977 TI - Thrombin as an adjuvant to reanastomosis of the fallopian tubes reduces implantations in the rabbit. AB - To study the efficacy of topically administered thrombin as an adjuvant in tubal microsurgery, 24 rabbits underwent a 1-cm resection and microsurgical anastomosis of both fallopian tubes and were randomized to either thrombin or cautery for hemostasis. Ovarian wedge biopsies were done on the left ovary. The animals were mated 4 to 5 weeks postoperatively with a buck of proven fertility. They were killed at 2 to 3 weeks' gestation to note the number of fetuses per patent tube and presence or absence of pelvic adhesions. There was no effect of topical thrombin on the crude pregnancy rate but it was associated with a marked reduction in the number of fetuses per patent tube, despite similar rates of pelvic adhesions between groups. Topically administered thrombin appeared to reduce fertility in this experimental model by an undefined mechanism. PMID- 3337978 TI - Tetanus--a continuing problem in minor injuries. AB - Tetanus is rare in North America because of highly effective specific immunization programs. Nevertheless, 15 patients with generalized tetanus were treated at the Vancouver General Hospital over a 20-year period; 10 of them were over 50 years of age. Two patients had no injury and 12 had suffered only minor wounds. None had received previous immunization and, even after wounding, prophylaxis was unsatisfactory in all cases. Nine patients required intensive care and two died. Positive cultures were obtained in only two cases. Four recommendations are made to prevent tetanus: (a) all wounds should be considered "tetanus-prone", (b) an accurate history of immunization should be obtained, (c) more attention should be given to prophylaxis at the time of injury and (d) patients should record vaccinations. PMID- 3337979 TI - The dream of reason. PMID- 3337980 TI - Route of administration of influenza vaccine. PMID- 3337981 TI - Indirect death from ingestion of toxic mussels. PMID- 3337982 TI - Ribavirin aerosol therapy: safety for staff. PMID- 3337983 TI - New form for documenting cardiac arrest. PMID- 3337984 TI - Maternal and neonatal outcome in pregnancies with no risk factors. PMID- 3337985 TI - Calcium supplements and arthritis. PMID- 3337986 TI - New directions for the hospital blood transfusion service. PMID- 3337987 TI - Was it an adverse drug reaction? Try thinking of Bayes. PMID- 3337989 TI - Vitamin D supplementation for northern native communities. Indian and Inuit Health Committee, Canadian Paediatric Society. PMID- 3337988 TI - Physiologic consequences and complications of vasectomy. AB - Sterilization of men and women is the most popular method of contraception in Canada. The contraceptive effect of a vasectomy usually occurs within 3 months. The production of sperm, however, is not interrupted, and an increase in pressure proximal to the ligation site may cause rupture of the epididymis or the ductus deferens, with extravasation of spermatozoa and the formation of granulomas or sperm antibodies. Increased pressure may also explain the postvasectomy pain syndrome. PMID- 3337990 TI - Implications of caring for an aging parent. AB - The burden of care for the aged often falls on their adult children, who are themselves stressed by the developmental tasks of middle age. These people are frequently unprepared for the role of caregiver, in which they become parents to their own parents. The author describes the potentially turbulent effect of this role and discusses the origin of the stresses that the caregiver may experience. Doctors need to recognize and deal with the negative feelings, such as resentment, anger, frustration, ambivalence, guilt and demoralization, that may arise in adult children who care for their parents. These emotions must be put into proper context if the mental and physical health of the caregivers as well as the vital support they provide for their elderly parents are to be maintained. PMID- 3337991 TI - Public awareness of organ donation. AB - A telephone survey of public attitudes toward organ donation and transplantation was conducted in a community in southwestern Ontario. The subjects were selected at random; the response rate was 57%. Of the 50 respondents 62% stated that they had signed the organ donor card accompanying their driver's licence. These respondents were more likely than those who did not sign it to have discussed organ donation with their families. At least 80% of the respondents said they would agree to donate their organs and those of their next-of-kin, and 80% said that the organ donor card should be considered a legal document. Organ transplantation was regarded by all but one respondent as an acceptable medical procedure. Also discussed were concerns about organ donation and possible strategies to improve the availability of organs for transplantation. PMID- 3337993 TI - Illicit pleasure. PMID- 3337992 TI - Ottawa team first to use laser to clear coronary artery. PMID- 3337994 TI - Hawkesbury Hospital: small-town miracle or plain common sense? PMID- 3337995 TI - Abuse of elderly subject of Toronto conference. PMID- 3337996 TI - Geriatric medicine in Britain: we could learn something. PMID- 3337997 TI - FPs who don't practise obstetrics may still face birth-related legal action. PMID- 3337998 TI - Is prehospital advanced life support really necessary? PMID- 3337999 TI - CPR: is there a better method? PMID- 3338000 TI - Loonie dilemma. PMID- 3338001 TI - Seizure during urologic procedure. PMID- 3338003 TI - Clarifying requirements for manuscripts. PMID- 3338004 TI - Uniform requirements for manuscripts submitted to biomedical journals. International Committee of Medical Journal Editors. PMID- 3338002 TI - Medical school: your chance of getting in is better in the US. PMID- 3338006 TI - Mussel mystery: "the more you know, the more you don't know". PMID- 3338005 TI - Massive overdose of colchicine. PMID- 3338007 TI - What you should know about HSOs. PMID- 3338008 TI - Health care for seniors: a new and burgeoning market. PMID- 3338009 TI - Health and Welfare responds to CMA resolutions, supports AIDS stand. PMID- 3338010 TI - Get-rich-quick schemes make some doctors poor quickly. PMID- 3338011 TI - Responses to chemotherapy or chemohormonal therapy in advanced breast cancer patients treated previously with adjuvant chemotherapy. A subset analysis of CALGB Study 8081. AB - The Cancer and Leukemia Group B (CALGB) evaluated the response to subsequent chemotherapy or chemohormonal therapy in 46 patients with advanced breast cancer treated previously with adjuvant chemotherapy that had been completed 6 months or more before protocol entry. The results were compared with 379 patients in the same study who had not received prior adjuvant chemotherapy. The patients were treated with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH), and 5-fluorouracil (CAF), with or without tamoxifen. There was no difference in response rate, response duration, time to treatment failure, or survival between patients who had received prior adjuvant chemotherapy and those who had not. The addition of tamoxifen to CAF failed to enhance response rates or response durations in all subgroups. Women who relapsed 6 months or more after completion of adjuvant chemotherapy did not have inherently drug-resistant tumors. They responded to standard CAF chemotherapy with the same response rate and survival as patients untreated previously with chemotherapy. PMID- 3338013 TI - Brain tumors in the very young child. Postoperative chemotherapy in combined modality treatment. AB - Twelve consecutively diagnosed children with brain tumors, ages 7 to 27 months, were treated by a combined-modality approach featuring aggressive surgical resection followed by chemotherapy and delayed irradiation. Patients received multiple clinical neurologic examinations and psychological evaluations, as well as diagnostic imaging studies, to monitor the efficacy of chemotherapy and toxic effects of therapy. Six of the eight children with residual tumor evident postoperatively on computed tomography scans had objective responses to chemotherapy. The efficacy of chemotherapy was further demonstrated by the lack of disease progression for 7 months or longer in eight children, seven of whom remain free of tumor 19 to 57 months (median, 28 months) from the date of diagnosis. The neurologic status of ten patients improved during treatment. Developmental progress was normal in two, low average in three, and frankly deficient in four of ten children formally evaluated. These results indicate that postoperative chemotherapy, added to a regimen of surgical resection and delayed irradiation, prolong survival with only minimal short term neurotoxicity in the majority of very young children with malignant brain tumors. PMID- 3338012 TI - DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens. AB - Breast cancer proliferative capacity as determined by the DNA thymidine labeling index, along with estrogen and progesterone receptor status, is highly predictive for risk of relapse and overall survival. Recently, DNA ploidy and proliferative capacity (S-phase fraction [SPF]) as determined by flow cytometry have also shown significant prognostic value. The authors have developed a technique which allows a 50 to 100 mg aliquot of the same frozen breast tumor specimen routinely employed in steroid receptor assays, to be assayed for both DNA ploidy and SPF by flow cytometry. Of the 1331 tumors examined, DNA histograms were evaluable for ploidy in 89% (1184) of specimens examined; 57% of these were aneuploid. Adapting a trapezoidal model to estimate SPF in both diploid and aneuploid tumors, the authors found 81% (1084) to be evaluable for SPF, with a median SPF of 5.8% for the entire population. The median SPF was significantly lower in diploid tumors (2.6%) than in aneuploid tumors (10.3%, P less than 0.0001). Both aneuploidy and high SPF were strongly associated with absence of steroid receptors. Aneuploid tumors showed more striking differences in the frequency of high S-phase values with respect to receptor status and age or menopausal status, whereas diploid but not aneuploid tumors showed lower SPF in node-negative versus node-positive patients. Because it is particularly important to identify the high-risk minority of node-negative patients, the authors examined the node-negative group separately. High SPF subgroups appeared in each category of receptor status and age or menopausal status within the node-negative group, suggesting that SPF will be an independent prognostic factor. With the DNA flow cytometric methods used here, it is now practical to determine ploidy and SPF for nearly every breast cancer patient. These factors, which show associations with established prognostic factors, such as receptor status can now be fully evaluated for their prognostic significance in broad patient populations. PMID- 3338014 TI - Maintenance chlorambucil after CVP in the management of advanced stage, low-grade histologic type non-Hodgkin's lymphoma. A randomized prospective study with an assessment of prognostic factors. AB - One hundred sixty-two patients with Stages III and IV non-Hodgkin's lymphoma of low-grade histologic type were treated with combination chemotherapy using cyclophosphamide, vincristine, and prednisolone (CVP) followed by radiotherapy to sites of previous bulk disease. The patients were randomized to receive either follow-up alone or "maintenance" chemotherapy with 2 years of intermittent chlorambucil. A complete remission was obtained in 56% of patients and the median survival was 64 months (median follow-up, 74 months). Multivariate analysis revealed stage (P less than 0.0001) and Karnofsky performance status (P = 0.021) to predict complete response (CR) and the achievement of a CR (P less than 0.0001), female sex (P = 0.008), the absence of bulk disease (P = 0.038) and low serum alkaline phosphatase (P = 0.002) to predict prolonged survival. The median relapse-free survival (RFS) of the complete responders was 41 months. A prolonged RFS was predicted by low stage (P = 0.014), low serum lactic dehydrogenase (LDH) (P = 0.045) levels, and by the administration of maintenance chlorambucil (P = 0.045). A prolonged survival of the complete responders was predicted by a low number of nodal sites of involvement with lymphoma at presentation (P = 0.022) and lack of liver involvement (P = 0.011). The administration of oral maintenance therapy with chlorambucil for a full 2 years was only possible in 38% of patients, mainly because of progression of disease and the induction of thrombocytopaenia, but despite this it prolonged the median RFS by 38 months and its use could be considered when future studies are being designed. PMID- 3338015 TI - Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients. AB - Cyclophosphamide is an alkylating agent used intravenously or orally in the treatment of both malignant and nonneoplastic diseases. A known adverse effect of such treatment is hemorrhagic cystitis. A series of 100 patients with hemorrhagic cystitis induced by cyclophosphamide was studied. Major symptoms were gross hematuria (78%) and irritative voiding symptoms (45%). Microhematuria developed in 93% of patients. Hemorrhagic cystitis developed at significantly lower doses and shorter durations of therapy in patients treated intravenously than in patients treated orally. Cystectomy was required in nine patients and bladder cancer developed in five. Urine cytologic study, urinalysis, and cystoscopy are important in the diagnosis of hemorrhagic cystitis, and these studies plus periodic excretory urography are important for surveillance. In addition, new methods of protecting against the urotoxicity are available. PMID- 3338016 TI - Oral verrucous carcinoma. Treatment with radiotherapy. AB - Fifty-two cases of oral verrucous carcinoma treated with radiotherapy at the Regional Cancer Centre, Trivandrum, Kerala, India in 1982 were evaluated to determine the distribution within the oral cavity, clinical extent, and effectiveness of radiotherapy in controlling the disease. The most common site was the buccal mucosa. Fifty percent of the patients had clinically negative regional lymph nodes and 33% were in earlier stages (T1, T2, N0, and M0). The overall 3-year no evidence of disease (NED) survival rate was 44%. The 3-year NED survival rate with radium implant was 86%. We cannot comment on anaplastic transformation after radiotherapy because our treatment failures have not been subjected for biopsy concerning this matter. Because the results are comparable with those of well-differentiated squamous cell carcinoma, we think that the treatment policies advocated for oral squamous cell carcinoma are also applicable to oral verrucous carcinoma. PMID- 3338017 TI - Susceptibility to 1,2-dimethylhydrazine-induced colonic tumors and epithelial cell proliferation characteristics of F1, F2, and reciprocal backcrosses derived from SWR/J and AKR/J parental mouse strains. AB - Hybrid crosses were performed between SWR/J, a strain highly sensitive to 1,2 dimethylhydrazine (DMH), and AKR/J, a strain highly resistant to the carcinogen. F1 and F2 and reciprocal backcrosses were tested to determine if proliferative characteristics such as high activity, wide compartment (PC), and a large S-phase population in the middle third of crypts were linked to susceptibility and inherited as a dominant autosomal trait as was reported for DMH tumor response. A blend of resistant and sensitive tumor and proliferative characteristics was observed in the F1 and F2 crosses. A tumor incidence of 43.7% in the F1 and 52% in the F2 was obtained rather than the respective 100% and 75% expected frequencies. One week after the sixth injection of DMH, the incidence of focal areas of atypism (FAA) in the backcross to resistance (BCR) and the backcross to sensitivity (BCS) was the same (4.1 per FAA-bearing animal). This suggested that the response to the carcinogen was similar in both groups up to this point. Yet 20 weeks later, the BCR had a 7.3% tumor incidence, far lower than the 50% incidence expected. The BCS had an incidence of 98.6%, not unlike SWR frequencies and close to the expected 100% tumor incidence. Proliferative characteristics in the backcrosses, however, did not revert to parental levels. Instead, the labeling index (LI) or percentage of S-phase cells to total cells scored was significantly higher in the BCR than in the BCS (10.2% +/- 3.2% versus 8.1% +/- 2.2%, P less than 0.02). This study has shown that in crosses between these two strains (SWR/J and AKR/J), susceptibility to DMH-induced tumor is not inherited as a dominant trait. Neither are the proliferative characteristics of the colonic mucosa inherited in a simple Mendelian manner nor are the kinetic properties of the epithelial cells linked to DMH tumor susceptibility. It is suggested that the parental AKR/J strain may contribute a protective or resistant factor, that is, a repressor gene, which impedes the progression of carcinogen-induced foci of dysplasia to colonic neoplasia. PMID- 3338018 TI - Characterization and comparison of two newly established Epstein-Barr virus negative lymphoma B-cell lines. Surface markers, growth characteristics, cytogenetics, and transplantability. AB - Two Epstein-Barr virus (EBV)-negative lymphoma B-cell lines, HBL-1 and HBL-2, were established from a pleural effusion and a lymph node biopsy of two patients with diffuse large cell lymphoma. HBL-1 and HBL-2 showed the characteristics of activated B-cells in B-cell lineage, as did original lymphoma cells. Chromosome analyses revealed that HBL-1 exhibiting 14q+ marker-positive lymphoid cancer showed a new subclass of 14q32 translocation resulting from a translocation between chromosomes 14 and 16, which had been masked in a complex translocation involving five chromosomes, and that HBL-2 had a 14q+ marker chromosome, the result of an 11;14 translocation [t(11;14)(q13;32)]. Successful heterotransplantation into athymic nude mice demonstrated tumorigenicity of HBL-1 and HBL-2. The transplantability and tumor growth rate of HBL-2 were higher and more rapid than those of HBL-1. HBL-1 and HBL-2 appear useful for facilitating therapeutic investigations as well as immunologic and oncogenic studies in B-cell lymphomas. PMID- 3338019 TI - Acetylcholinesterase and butyrylcholinesterase activities in human thyroid cancer cells. AB - The appearance and distribution of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in 12 human thyroid cancers and three normal thyroids were examined by electron microscopic study with indirect thiocholine method. The demonstration of AChE and BuChE activities in only two of nine cases of follicular and papillary carcinoma examined and none of the three cases of medullary carcinoma shows that the cholinesterases are not specific enzymes for the thyroid tumors. In normal thyroid tissue samples examined, no activities of AChE and BuChE were detected. On ultrastructural level AChE reaction product was revealed in the perinuclear space, in the endoplasmic reticulum, and in the Golgi complex of some but not in all cells in less-differentiated regions of the tumors. In contrast to the distribution of AChE, no staining for BuChE was noted in the Golgi elements. Ultrastructural localization of AChE activity in the thyroid cancer cells corresponds exactly to the current understanding of glycoproteins synthesis and processing in normal cells. The authors postulate that the copy of AChE gene suppressed in normal thyroid epithelium cells may be expressed in some follicular thyroid carcinoma cells. Their hypothesis is logical on the basis of recent finding of a significant homology between AChE and thyroglobulin. PMID- 3338020 TI - Immunohistochemical localization of pulmonary surfactant apoproteins in various lung tumors. Special reference to nonmucus producing lung adenocarcinomas. AB - Eighty-nine primary lung carcinomas and 23 metastatic lung tumors were immunohistochemically studied for the expression of pulmonary surfactant apoproteins, by using monoclonal (PE-10) and polyclonal antibodies. Surfactant apoprotein was demonstrated in the cytoplasm and/or nuclear inclusion bodies of only primary lung adenocarcinomas (36 of 75 cases), not in any other histologic type of primary lung carcinoma or in metastatic lung tumors. In primary lung adenocarcinoma, although typical type II pneumocyte type adenocarcinoma was not included in the current series, the majority of surfactant apoprotein-positive single cell type tumors were of the Clara cell type, with a single bronchial surface epithelial cell type, according to the light microscopic subclassification of adenocarcinoma cells. The Clara cell type adenocarcinomas could at times be distinguished only with difficulty from adenocarcinoma of type II pneumocyte type. Normal and hyperplastic type II pneumocytes were of course positive for surfactant apoprotein in the cytoplasm. However, none of the positive cells could definitely be identified as Clara cells in non-neoplastic lungs. The findings obtained in this study indicate that surfactant apoprotein is a good marker to distinguish adenocarcinoma of the lung from other histologic types of lung cancer and from neoplasms metastatic to the lung, and that type II pneumocytes and Clara cells, non-neoplastic and neoplastic, are morphologically and functionally closely related and might belong to the same cell lineage. PMID- 3338021 TI - Architectural (FIGO) grading, nuclear grading, and other prognostic indicators in stage I endometrial adenocarcinoma with identification of high-risk and low-risk groups. AB - We studied 164 cases of Stage I endometrial adenocarcinoma to determine the relative prognostic value of International Federation of Gynecology and Obstetrics (FIGO) and nuclear grading systems. Other factors known to be of prognostic value in endometrial carcinoma also were evaluated. Both the FIGO and nuclear grading systems correlated with five-year mortality rate from cancer. Nuclear Grade 3 proved to be a superior predictor of fatal outcome (nine of 13 [69%] ) over FIGO Grade 3 (four of 13 [31%]). We advocate the combined use of FIGO and nuclear grading systems, along with other prognostic parameters, for the detection of most patients with fatal cancer. PMID- 3338022 TI - Ovarian mixed-epithelial papillary cystadenomas of borderline malignancy of mullerian type. A clinicopathologic analysis. AB - Borderline tumors with papillae that are architecturally similar to those of serous tumors but with a lining of more than one mullerian cell type have not been well characterized in in the literature. We have studied 36 such tumors. The patients averaged 35 years of age. Twenty-two percent of the tumors were bilateral; all were confined to the ovaries as confirmed at operation. Fifty three percent were associated with endometriosis. Follow-up information was available on 34 patients for a mean interval of 4.8 years. A tumor developed in the contralateral ovary in one patient 2 years after unilateral salpingo oophorectomy. Three patients had pelvic recurrences between 7 months and 3 years, but all of them were successfully treated and none have died. These tumors differ clinically and pathologically from intestinal-type mucinous borderline tumors, but they have many similarities with mullerian mucinous borderline tumors and, to a lesser extent, with serous borderline tumors. PMID- 3338023 TI - Large acinar atypical hyperplasia and carcinoma of the prostate. AB - Step-sections of 429 whole prostate glands were studied. Large acinar atypical hyperplasia was graded as mild, moderate, and severe based on the degree of cellular anaplasia. The relationship between atypical hyperplasia and prostatic carcinoma was investigated. There was a strong association between prevalence and grade of atypical hyperplasia and prostatic carcinoma in patients up to 60 years old. Beyond the age of 60 no association was detected. In the younger age groups (36 to 60 years) atypical hyperplasia was found in 86.8% of prostates with carcinoma, but only in 37.9% of benign glands. Corresponding figures for the over 60 age group were 68.8% and 65.1%, respectively. A biologic explanation of the association between atypical hyperplasia and carcinoma in the younger age groups has been proposed. It was suggested that these men with atypical hyperplasia, particularly with severe atypical hyperplasia, have a greater risk for developing prostatic carcinoma. PMID- 3338024 TI - Interdigitating cell sarcoma. A morphologic, immunohistologic, and enzyme histochemical study. AB - A 58-year-old man presented with an unusual sarcoma of the cervical lymph node. The tumor also involved the mesenteric lymph node and jejunum. Tumor cells possessed intracytoplasmic S100 protein, Leu-3a (T4), and HLA-DR antigens. The neoplastic cells also showed membranous ATPase activity. LeuM1, T6, Leu1, Leu2a, B1, lysozyme, and immunoglobulin were not recognized. Their fine structure was similar to that of interdigitating cells. These data are consistent with derivation from lymph node interdigitating reticulum cell. PMID- 3338025 TI - Interval-by-interval Cox model analysis of 3680 cases of intraocular melanoma shows a decline in the prognostic value of size and cell type over time after tumor excision. AB - In a selected group of 3680 patients treated by ocular excision for uveal melanoma, 1178 deaths were attributed to this tumor during 20 years following ocular excision. Survival time was divided into intervals containing an equal number of deaths, and coefficients of the Cox statistical model were independently derived for each interval. This analysis revealed a statistically significant decline over time in the prognostic value of largest tumor dimension (LTD) and Callender cell type (CT). Mathematical considerations suggest that the prognostic value of parameters derived from other cancers may also decline with time following excision of the primary tumor. PMID- 3338027 TI - Incidence of cancer of the esophagus in the US by histologic type. AB - Data from nine US population-based cancer registries participating in the Surveillance, Epidemiology, and End Results (SEER) program from 1973 through 1982 were analyzed to examine demographic characteristics related to the occurrence of the two major types of cancer of the esophagus. The overall annual incidence rate per 100,000 persons was 2.6 for squamous cell carcinoma and 0.4 for adenocarcinoma. The sex ratio for adenocarcinoma varied from one age group to the next and was highest in the 50- to 59-year-old group. It was relatively the same for squamous cell carcinoma. The male-to-female ratio was higher for adenocarcinoma (seven in whites and 10 in blacks) than for squamous cell carcinoma (three and four, respectively). The highest sex-specific ratio for adenocarcinoma occurred in the lower third of the esophagus. Blacks had a fourfold to fivefold higher rate of squamous cell carcinoma than whites, but the rate of adenocarcinoma in blacks was 30% of the rate in whites. The incidence of squamous cell carcinoma in black men and women increased by approximately 30% between 1973 and 1982, and the rate of adenocarcinoma among white men increased 74%. Nearly half of the squamous cell carcinomas occurred in the middle of the esophagus, whereas the majority (79%) of the adenocarcinomas arose in the lower third. These data suggest that the two major histologic types of esophageal cancer may be of different etiologic origin. PMID- 3338026 TI - Natural history of gastric adenomas in patients with familial adenomatosis coli/Gardner's syndrome. AB - The natural history of gastric adenomas was studied in 26 patients with familial adenomatosis coli (FAC)/Gardner's syndrome. The patients were followed for an average of 6.8 years (1 year, 5 months to 15 years 4 months) and examined repeatedly using gastric radiography, endoscopy, and biopsy. Gastric adenomas were present in 13 (50%). During the follow-up period, there was a new appearance of gastric adenomas in six patients but no distinct change in number, size, and histologic features in the remaining seven patients. In a 51-year-old man, an antral adenoma that measured 13 mm in diameter and had an irregular central depression did not change in size or morphology during 4 years and 1 month, but malignant change was evident at the time of endoscopic biopsy. The findings indicate that in patients with this disease, gastric adenomas require careful repeated follow-up examinations using endoscopic biopsy and, if feasible, endoscopic removal is recommended. PMID- 3338028 TI - Cholecystectomy and adenomatous polyps of the colon in women. AB - The relationship between prior cholecystectomy and colon cancer in women has been a subject of recent research interest. No study has yet reported on cholecystectomy and adenomatous polyps, a precursor lesion for most colon cancers. This pilot case-control study interviewed 245 women who had undergone colonoscopy between 1983 and 1985 at Columbia-Presbyterian Medical Center with a structured telephone-administered questionnaire. Fifty-six were colon cancer cases, 105 were adenomatous polyp (AP) cases, and 84 were controls (without colonic neoplasia). Adjusted for age and educational attainment, the odds ratio for prior cholecystectomy among colon cancer cases compared to controls was 1.79 (95% confidence limits, 0.59 to 5.44) and 2.26 for right-sided colon cancer cases (95% confidence limits, 0.61 to 8.42). Despite a lack of statistical power, these estimates are consistent with earlier reports. The odds ratio for adenomatous polyp cases was 1.02 (95% confidence limits, 0.40 to 2.64), suggesting no association between prior cholecystectomy and adenomatous polyps. These preliminary findings are currently being explored in a large-scale case-control study. PMID- 3338029 TI - Effect of the type of cigarette smoked on bladder cancer risk. AB - The relationship between the type of cigarette smoked and bladder cancer risk was examined in data from a hospital-based case-control study. Information on smoking, including filtered and nonfiltered cigarette use, was available for 899 male and 427 female patients and 2713 male and 1243 female age-matched controls interviewed in 20 hospitals from nine cities in the US between 1969 and 1984. Smokers of filtered cigarettes had a slightly reduced risk of bladder cancer relative to smokers of nonfiltered cigarettes (odds ratio 0.64, 95% confidence interval 0.38 to 1.10 among male smokers; odds ratio 0.74, 95% confidence interval 0.37 to 1.48 among female smokers). In both sexes there was no statistically significant reduction in risk among switchers from nonfiltered to filtered cigarettes compared with lifetime nonfiltered cigarette smokers (odds ratio 0.93, 95% confidence interval 0.71 to 1.24 among male smokers; odds ratio 0.76, 95% confidence interval 0.40 to 1.46 among female smokers). The causal implications of these findings, in particular a possible initiation effect of tobacco smoke on bladder carcinogenesis, are discussed. PMID- 3338030 TI - Management of low-grade gliomas of the optic nerve and chiasm. AB - Thirty-six patients were evaluated between 1965 and 1983 for glioma of the optic nerves and/or chiasm. Median follow-up was 10.2 years. Pathologic verification was obtained in 32 patients. Tumor initially confined to the optic nerve recurred in one of five patients after complete resection. The actuarial survival for 25 patients irradiated for biopsy-proven glioma of the optic chiasm was 96%, 90%, and 90% at 5, 10, and 15 years, respectively, and the progression-free survival was 87% at 5, 10, and 15 years. Vision stabilized or improved in 86% of patients after radiotherapy. Patients irradiated to a dose greater than a NSD of 1385 ret had a significantly improved progression-free survival (P = 0.015). One serious complication occurred after a dose of 1533 ret. The recommended radiation dose for optic glioma is 45 to 50 Gy with 1.8 Gy fractions. PMID- 3338031 TI - Combined radiation and chemotherapy as primary management of adenocarcinoma of the esophagus and gastroesophageal junction. AB - Between January 1981 and December 1986, 20 patients with adenocarcinoma of the esophagus and gastroesophageal junction were entered into a prospective study involving combined radiation therapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin) as primary management. Nine patients with Stage I or II disease received definitive treatment consisting of 6000 cGy in 6 to 7 weeks and 5-FU (1000 mg/m2/24 hours) as a continuous intravenous (IV) infusion for 96 hours starting on days 2 and 29. Mitomycin (10 mg/m2) was administered as a bolus injection on day 2. Ten patients with extraesophageal and disseminated disease (Stages III and IV) and one patient with an unresectable anastomotic recurrence were considered palliative. Generally the palliative regimen did not differ from the definitive except for the radiation dose which in seven of the 11 patients was less than 6000 cGy (4000-5600 cGy). The range of follow-up was 6 to 74 months and no patient was lost to follow-up. Seven of the eight evaluable definitively treated patients were complete responders. The median relapse-free survival was 10 months and the median survival was 15 months in this group. In the palliative group, six of nine evaluable patients had relief of dysphagia until death or last follow-up with a median duration of 8 months. Our results indicate that combined modality treatment with infusional 5-FU, mitomycin, and radiation is an effective and well-tolerated treatment for adenocarcinoma of the esophagus and gastroesophageal junction. This treatment regimen offers palliation and some chance for cure to those patients who are inoperable, unresectable, or who refuse surgery. PMID- 3338033 TI - Second primary cancer after treatment for cervical cancer. Late effects after radiotherapy. AB - Using data from the population-based Danish Cancer Registry, the relative risk (RR) of second primary cancer was assessed among 24,970 women with invasive cervical cancer (1943-1982) and 19,470 women with carcinoma in situ of the cervix. The analysis was stratified according to treatment with (+) and without ( ) radiation. For all second primaries combined, a RR+ = 1.1 (95% confidence interval (CI) = 1.06-1.18) and a RR- = 1.3 (95% CI = 1.13-1.40) was observed after invasive cervical cancers and a RR+ = 3.5 (95% CI = 1.4-7.2) and RR- = 1.1 (95% CI = 0.7-1.6) following in situ cancer. The small overall excess of second primary cancer is accounted for by an increase of some cancers such as lung, bladder, and a concurrent decrease in others such as breast. Although not statistically different from nonirradiated, the RR increased with time since treatment among irradiated invasive cervical cancer patients in organs close to and at intermediate distance from the cervix, reaching a maximum after 30 or more years of follow-up (RR = 1.9; 95% CI = 1.4-2.5). Altogether, for these sites an excess of 64 cases per 10,000 women per year were attributable to radiation among survivors of 30+ years. The highest risks among long-term survivors were observed for the following: other genital organs (RR = 5.8; 95% CI = 1.8-13.0) bladder (RR = 5.5; 95% CI = 2.8-9.5), connective tissue (RR = 3.3; 95% CI = 0.4-12.0), stomach (RR = 2.5; 95% CI = 1.1-4.7) and rectum (RR = 2.4; 95% CI = 1.1-4.6). A significant deficit of risk for breast cancer (RR = 0.7, 95% CI = 0.6-0.8) was observed for 10+ years, may be attributable to the effect of ovarian ablation by radiotherapy. It is speculated that the same effect also may explain the observed deficits of brain tumors (RR = 0.6; 95% CI = 0.4-1.0) and skin melanomas (RR = 0.6; 95% CI = 0.3-1.0). It is concluded that cancers attributable to radiation, apart from acute nonlymphocytic leukemias, tend to appear late (10 or more years after radiotherapy), and that the risk remains elevated for more than 30 years. PMID- 3338032 TI - Pharyngo-cutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole. AB - The development of a pharyngocutaneous fistulae is a major complication after total laryngectomy. In Denmark radiotherapy is the primary treatment for all laryngeal carcinomas. Based on the experience with conventional daily irradiation, a split-course radiation schedule was introduced in 1978. The charts of 106 consecutive patients laryngectomized for recurrence in the years 1975 to 1984 were examined. Thirty-four patients developed a fistula. An evaluation of the different radiotherapy schedules used during this period allowed a dose response curve to be constructed. It showed a pronounced increase of fistulae with high doses of radiotherapy. Split-course radiotherapy caused a rise in late complications and did not improve tumor control. Large field sizes increased the number of fistulae. High-dose fractions showed a surprisingly high incidence of late complications. Prophylactic metronidazole (introduced in 1980) resulted in a highly significant decrease in the frequency of postoperative fistulae. Patients in whom fistula formed were hospitalized for an average of 54 days, patients without, for 22 days. PMID- 3338034 TI - Changing expression of ABH blood group and cryptic T-antigens of noninvasive and superficially invasive papillary transitional cell carcinoma of the bladder from initial occurrence to malignant progression. AB - Thirteen patients who developed malignant progression after frequent recurrence of noninvasive or superficially invasive (Ta or T1) papillary transitional cell carcinoma of the bladder were studied for expression of ABH-antigens in tumor tissues throughout their clinical courses and cryptic Thomsen-Friedenreich antigen (T-Ag) expression in the tumor tissues was examined simultaneously in nine of them. Five patients who experienced recurrent bladder tumors for more than 5 years without any malignant progression were served as control. ABH antigens in initial tumors were negative in only two of 13 patients developing malignant progression and in two of five controls. Cryptic T-Ag was positive in all patients examined. Recurrent tumors revealed eliminated or decreased expression of ABH-antigens and cryptic T-Ag before malignant progression in, respectively, ten of 11 and six of nine patients with antigen-positive initial tumors. In contrast, recurrent tumor of controls with antigen-positive initial tumors showed neither elimination nor decrease in expression of antigens throughout their clinical courses. PMID- 3338035 TI - Modified properties of serum cholinesterases in primary carcinomas. AB - Cholinesterases were characterized in the serum of 77 treated and 11 untreated patients having primary carcinomas of various tissue origins and 21 healthy volunteers which served as controls. In most of the samples, pseudocholinesterase (BuChE) accounted for almost all cholinesterase (ChE) activity and was inhibited by the organophosphorous poison tetraisopropyl pyrophosphoramide (iso-OMPA). In samples from the tumor-bearing patients, ChE degraded 733 +/- 59 nmole acetylcholine/h/mg protein, lower than the 960 +/- 175 nmole/hour/mg levels measured in controls. Tumor serum ChE exhibited elevated sensitivity to 1,5-bis (4-allyldimethyl ammonium phenyl)-pentan-3-one dibromide (BW), the selective bisquaternary inhibitor of "true" acetylcholinesterase (AChE), with no correlation to age, sex, staging of tumor, presence of metastases or the specific treatment protocol, and with a different distribution pattern from the decrease in ChE specific activity or the sensitivity to iso-OMPA. In sucrose gradients, ChE sedimented as 12S in controls whereas in tumor serum samples from treated patients an additional component of 6 to 7 S, inhibited by both iso-OMPA and BW, also was detected. However, the ChE activity in serum of patients with diagnosed carcinomas before surgery and medical treatment appeared to be nondistinguishable from controls. These findings suggest that the modified properties of serum cholinesterases in carcinoma patients are not the result of the tumor itself, but that the common therapy protocols used in the treatment of primary carcinomas may cause the appearance of soluble ChE activity with properties of both AChE and BuChE, which accumulates in the serum. PMID- 3338036 TI - Inflammatory infiltrates and natural killer cell presence in human brain tumors. AB - Immunohistochemical analysis of subpopulations of inflammatory cells in 81 primary and secondary human brain tumors was done. Natural killer (NK) cells, representing non-major histocompatibility complex-restricted, spontaneous cytotoxicity and monocytic cells are virtually absent in infiltrates of gliomas and account only for a minor percentage of inflammatory cells in brain metastases of carcinoma and in craniopharyngeomas. Infiltrates in gliomas consist almost exclusively of T-cells of the suppressor/cytotoxic type whereas infiltrates in carcinoma metastases and craniopharyngeomas contain considerable numbers of T helper/inducer cells and B-cells. From this the authors conclude (1) that NK cells do not play a major role in tumor rejection, and (2) that the kind of inflammatory reaction does not depend upon the tumor site but more likely on the tumor type. No correlation between tumor differentiation and infiltrate composition is evident. PMID- 3338037 TI - Flow cytometric DNA analysis of medulloblastoma. Prognostic implication of aneuploidy. AB - Paraffin-embedded surgical specimens from 26 infants and children with medulloblastomas treated between 1972 and 1981 were examined for DNA ploidy by flow cytometry (FCM). All patients received a standard treatment (a combination of maximum debulking of medulloblastoma and postoperative craniospinal irradiation with a posterior fossa boost of 5000 rad or more). They were studied to correlate the results of the findings of FCM DNA analysis with their final outcome, DNA ploidy, and extent of tumor resection. All seven patients with totally resected aneuploid medulloblastoma are alive, whereas only one of six patients with subtotally resected diploid medulloblastoma is alive (P = 0.0047). The current study suggests both DNA ploidy and extent of surgical resection are the most important determinant of patients' prognosis. Patients in selected group, particularly those with subtotally resected diploid tumor, are advised to undergo aggressive adjuvant chemotherapy. PMID- 3338039 TI - Prognostication in soft tissue sarcoma. A model with four risk factors. AB - A multivariate analysis of risk factors for death due to tumor was performed in 82 patients with highly malignant, histologic Grades III and IV primary soft tissue sarcoma of the locomotor system. All the patients had been operated on with a wide or radical surgical margin. Male sex, histologic malignancy Grade IV, extensive tumor necrosis, and tumor size greater than 10 cm were identified as risk factors. Patients with no or one risk factor had a 6(10)-year survival rate of 100% (100%), equal to 96% (96%) in a group with Grade I and Grade II tumors operated on with the same margin. These two groups comprised 50% of all the patients operated on with a wide or radical margin. The 6(10)-year survival rate decreased to 75% (75%) for patients with two risk factors and to 33% (22%) for patients with three or four risk factors. The risk factor model also applied to 62 patients operated on with marginal surgery; and for patients with three or four risk factors, more extensive surgery only had a small effect on long-term survival. The model could be of value when eligibility criteria for trials with adjunctive chemotherapy are determined. PMID- 3338038 TI - The prognostic value and relationships of patient characteristics, estrogen and progestin receptors, and site of relapse in primary breast cancer. AB - Estrogen and progestin receptor levels (ER and PgR) in tumors from 506 patients with primary breast cancer diagnosed in 1979, 1980, and 1981 were measured by a Scatchard plot analysis. At a median follow-up time of 3.5 years the prognostic value of the receptor levels was evaluated and compared with other tumor and patient characteristics. No relation was found between receptor levels and tumor, lymph node, metastasis (TNM) classification or location of the primary tumor. A significant positive rank correlation was observed between ER and PgR levels (rs = 0.57) and between ER level and age of the patients (rs = 0.39, P less than 0.001). The observed association between ER level and menopause status could not be maintained after correction for age. Independent prognostic factors for overall survival were tumor size (P = 0.002), the number of positive lymph nodes (P less than 0.001), age at primary surgery (P less than 0.001), the PgR level of the tumor (P less than 0.001), but not ER level. Independent prognostic factors for relapse were tumor size (P = 0.003), number of positive lymph nodes (P less than 0.001), age (P = 0.006), menopause status (P = 0.02), PgR level (P = 0.007), but not ER level. Finally, for death rate after relapse the following prognosticators were identified: size of the primary tumor (P = 0.03), number of positive lymph nodes (P = 0.03), age (P = 0.003), site of relapse (P less than 0.001), ER level (P = 0.02), and PgR level (P = 0.04). Patients with tumors containing low positive PgR levels (10 to 20 fmol/mg protein) had a slightly better prognosis than patients with PgR-negative tumors. It is concluded that the PgR level of the primary tumor is a better prognosticator than the ER level. The ER offered no additional ability for discriminating between low- and high-risk patients once PgR was included in the model. In contrast, PgR was capable of improving on the discriminating ability of ER. In addition, patients with tumors containing both PgR and ER showed the best prognosis. Therefore, it is recommended that ER and PgR should be assayed in all breast cancer biopsies. PMID- 3338040 TI - Minute cancers arising de novo in the human large intestine. AB - In order to search for the histogenesis and progression of colorectal cancer, the background mucosas of 18 patients with a single colorectal cancer, apart from familial adenomatosis coli, were studied by a step sectioning method. Three early minute cancers (3-5 mm in diameter) were detected in the apparently normal mucosa, and two cancers in the adenoma (focal cancer in adenomatous polyp). The three early cancers had no evidence of preexisting adenoma, so they were considered to be de novo cancers. In form they were depressed, flat, and slightly elevated. In humans, de novo cancer has an important significance in histogenesis and treatment of colorectal cancer. Clinically, it is also important to recognize the early phase of colorectal cancer in flat type as well as polypoid type. PMID- 3338041 TI - Colorectal carcinoma in patients younger than 40 years of age. Montpellier Cancer Institute experience with 78 patients. AB - During an 18-year period, 2600 patients were treated for colorectal carcinoma in the Montpellier Cancer Institute. Of the 93 patients younger than 40 years of age (3.6%), 78 records were retrospectively studied. The overall 5-year survival rate was 30%. Their survival was not significantly affected by the site of the primary tumor, the degree of tumor differentiation, or sex. The only significant parameter was Dukes' staging at presentation (P less than 0.0001). An analysis of sites of recurrence revealed the frequency of liver metastasis, ovarian metastasis in women, and local recurrence of rectal cancer. Although the high failure rate in these areas clearly justifies aggressive combined therapy, the high frequency of inaugural Stage D patients (27%) and their short mean survival time (5 months), underline the crucial importance of early detection. However, it is unfortunate that colorectal cancer screening in young patients is difficult because of the low rates of precancerous states (4%). PMID- 3338042 TI - Malignant hemangiopericytoma in three kindred members of one family. AB - Three cases of malignant hemangiopericytoma in one family are reported. To our knowledge familial occurrence of malignant hemangiopericytoma has not been described before. Two of these lesions occurred in the head and neck region and one case presented as an intraabdominal tumor. Consanguinity of the parents seems to be likely, suggesting an autosomal recessive mode of inheritance in our family, whereas the similarity in age of onset in these three patients was apparent. PMID- 3338043 TI - Minnesota Multiphasic Personality Inventory-rated depression and the incidence of breast cancer. AB - Using data from the Walnut Creek Contraceptive Drug Study (a prospective study begun in 1969 and continuing to the present), Minnesota Multiphasic Personality Inventory-(MMPI) measured scores for depression of 8932 women were studied in relation to the incidence of breast cancer. No statistically significant association between MMPI scores for depression and the subsequent development of breast cancer was found. There was neither an association of risk of breast cancer with repression/sensitization as measured on the MMPI nor with scores on the MMPI lie scale. This study is unique because it represents the largest reported prospective cohort in which the association between depression and breast cancer development has been examined. PMID- 3338044 TI - Glandular neoplasia of the lung. A proposed analogy to colonic tumors. AB - In 62 consecutive resections for adenocarcinoma of the lung, 50 cases (81%) had single adenocarcinomas and 12 (19%) had multiple adenocarcinomas. In seven of these 12 patients, two adenocarcinomas were found. In the other five patients, the specimen contained a dominant adenocarcinoma and several 0.1- to 1-cm nodules of similar histologic appearance. In four of the 50 single tumor patients and one of seven double tumor patients, 1- to 2-mm nodules were found along with adenocarcinomas that we interpreted as being bronchioloalveolar tumors of uncertain malignant potential. An analogy is drawn between these four types of findings and single tumors of the colon, double tumors of the colon, polyposis syndromes, and tubular adenomas of the colon, respectively. PMID- 3338045 TI - Vascular and neural invasion in colorectal carcinoma. Incidence and prognostic significance. AB - The incidence and significance of histologic vascular and/or neural invasion in 77 patients with colorectal carcinoma treated over a 6-year period were analyzed retrospectively. Vascular invasion was found in 37.6% of patients and neural invasion in 14.3%. The following three types of vascular invasion were identified: tumor lining epithelium, tumor thrombi, and destruction of the vessel wall. The incidence of metastases in patients with vascular invasion was 60% as opposed to 17% in those without vascular invasions (P less than 0.0001). Survival in these patients was 29.7% and 62.2%, respectively (P less than 0.003). Metastases were found in 72.7% of patients with neural invasion, as opposed to 27% of those without neural invasion (P less than 0.01). Survival was 29.6% as opposed to 57.7% in those without neural invasion (P less than 0.003). Even among patients in the same Dukes' stage, prognosis, as determined by incidence of recurrence, metastases, and survival, was worse significantly among those patients demonstrating vascular invasion (P less than 0.03). Examination of patients with colorectal carcinoma for the presence of vascular and neural invasion may provide useful information for determining future treatment and prognosis. PMID- 3338046 TI - X-ray guided fine-needle aspiration for the cytologic diagnosis of nonpalpable breast lesions. AB - X-ray guided localization of 215 nonpalpable, mammographically detected, breast lesions for fine-needle aspiration biopsy was performed using a two-dimensional coordinate grid. Representative material was obtained in 64% of the lesions. Very strict criteria of representativity were observed. The sensitivity of the cytologic procedure was 92%, the specificity 95%, the predictive value of positive cytologic diagnosis 88%, and the predictive value of a negative cytologic diagnosis 97%. Potential pitfalls in the localization and aspiration procedures are discussed. The results of cytologic examination should always be correlated with the mammographic findings, and further diagnostic and therapeutic decisions should be based on both modalities. In this setting, x-ray guided fine needle aspiration cytologic study is a highly valuable diagnostic tool. PMID- 3338047 TI - Preoperative staging of primary breast cancer. A multicentric study. AB - This article reports on a consecutive series of 3627 breast cancer (BC) patients undergoing preoperative staging by chest x-ray (CXR), bone x-ray (BXR) or bone scintigraphy (BS), and liver ecography (LE) or liver scintigraphy (LS). The detection rate (DR) of preclinical asymptomatic distant metastases depended on the T and N category (TNM classification system), and was very low (CXR: 0.30%, BXR: 0.64%, BS: 0.90%, LE: 0.24%, LS: 0.23%). The sensitivity, determined after a 6-month follow-up, was below 0.50% for all tests. The highest value (0.48%) was recorded for BS, which also had the lowest specificity (0.95%). The entire preoperative staging policy using the studied tests seems questionable due to poor sensitivity and an extremely low DR of distant metastases. PMID- 3338049 TI - Carcinomas in children. Clinical and demographic characteristics. AB - Carcinomas occur rarely in children and adolescents. Despite their rarity, these tumors present a unique opportunity to assess theories of origin because the interval from birth to tumor onset is relatively short compared with that seen in adults. We describe the clinical and demographic characteristics of 151 patients younger than 20 years of age with carcinomas who were treated at a pediatric cancer center having a large referral area. Incidence data for the major types of carcinomas in children, based on unpublished data provided by the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER), also are reported. PMID- 3338048 TI - The value of bone marrow biopsy in breast cancer at the time of first relapse. A prospective study. AB - The value of bone marrow biopsy (BMB) in advanced breast cancer at the time of first relapse was studied in a prospective manner. Bone marrow biopsy was performed in 142 consecutive unselected metastatic patients: 129 at the time of first recurrence, and 13 in patients with metastases at the time of first diagnosis. Overall, BMB was positive in 32 patients (23%). In the group with negative bone x-ray, it was positive in two patients of 84 (2%); both of them had doubtful scan. In the group with positive x-ray, BMB resulted positive in 30 of 58 (52%). There was a significant correlation between number of bone segments radiologically involved and BMB positivity rate, ranging from 15% in the patients with only one, to 68% in those with more than three sites involved (P = 0.02). Patients with x-ray evidence of metastases in the pelvis had significantly higher rate of BMB positivity (67% versus 32%; P = 0.02). The median survival time from the first relapse was 153 weeks in BMB-negative cases and 149 in positive ones. Considering only the patients with demonstration of bone invasion obtained with either or both x-ray and BMB, 34/62 patients had positive BMB (55%). In these cases BMB was found more often positive in patients 50 years or younger than in patients older than 50 years (80% versus 47%; P = 0.05); the median survival time was longer, but not significantly, in BMB-positive patients than in negative ones (149 weeks versus 119; P = 0.3). The authors conclude that BMB is not required in common restaging procedure when both bone survey and scan are negative. Bone marrow biopsy results are more often positive in younger patients and survival is not negatively affected by bone marrow invasion as diagnosed by BMB. PMID- 3338051 TI - Incidental carcinoma of the colorectum at autopsy and its effects on the incidence and future trends of colorectal cancers in Singapore. AB - Ten incidental invasive carcinomas (two early carcinomas involving the submucosa, and eight advanced carcinomas involving the muscularis propria or beyond) of the large intestine were discovered in a series of 1014 consecutive autopsies. All occurred in Chinese aged 60 years and older, constituting a prevalence rate of about 3% in this age group. If unsuspected colorectal carcinomas in Chinese Singapore residents aged 60 years and older exist in those who died in 1984 to the same extent as that noted in this autopsy study, it was estimated that 146 additional cases would have been added to the Cancer Registry in that year. This would constitute 47.9% of the total number of colorectal cancers diagnosed in this age group in 1984. This potential contribution has to be taken into consideration in epidemiologic studies on the incidence and future trends of colorectal cancers in Singapore. It was observed further that incidental carcinomas were found predominantly in the ascending colon. With more frequent use of colonoscopy, the incidence of right-sided cancers of the large bowel may be expected to increase. The current underdiagnosis of ascending colon carcinomas has to be taken into consideration when any future increase in right-sided cancers of the large bowel is observed. PMID- 3338050 TI - Cancer in the respiratory organs of Swedish farmers. AB - In a cohort of 254,417 male Swedish farmers (4,330,717 person-years) the incidence of cancer of the respiratory organs was compared to a reference cohort of 1,725,845 men (30,131,664 person-years) employed in other economic activities than agriculture or forestry. In the study cohort 1450 cases of cancer in the respiratory organs were found in 1961 to 1979 resulting in an estimated relative risk (RR) of 0.38 (95% confidence interval [CI]: 0.36-0.40). For cancer of trachea, bronchus and lung, the decreased risk was equal for adenocarcinoma and squamous cell carcinoma. No time related trend in RR for any of the histologic subtypes could be seen. However, for squamous cell carcinoma in nose and nasal sinuses RR has increased from 0.42 (95% CI: 0.20-0.80) in 1961 to 1966 to 2.06 (95% CI: 1.22-3.50) in 1974 to 1979. PMID- 3338052 TI - A pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumors. AB - A pilot study was performed to investigate the toxicity and therapeutic effect of radiolabeled antibody administered intrathecally in patients with leptomeningeal tumors. Five patients who failed conventional therapy received between 11 mCi and 40 mCi of radiolabeled antibody. The choice of antibody varied depending on the immunophenotype of the tumor. Therapy was well tolerated generally, with minimal acute toxicity. Four of five patients achieved an objective response to treatment that has been sustained for a period varying from 7 months to 2 years. No clinical signs of chronic toxicity have been observed in patients 1 and 2 years after therapy. PMID- 3338053 TI - Recombinant alfa-2b-interferon therapy in untreated, stages A and B chronic lymphocytic leukemia. A preliminary report. AB - Ten patients with B-chronic lymphocytic leukemia (B-CLL) (Six Stage A and four Stage B), who had not received therapy previously, were treated with recombinant alfa-2b-interferon (Schering Corporation, Kenilworth, NJ). The low dose of 1.5 MU was administered by intramuscular (IM) injection three times a week for the first week. The dose was increased to 3.0 MU thereafter until 3 months of therapy were completed. In the responding patients, treatment was continued in the same dose and schedule for 3 additional months. Interferon was tolerated without major toxicity by most patients. Objective tumor response (one complete response and four partial hematologic responses [PHR]) was observed in five of ten patients (50%). Severe autoimmune hemolytic anemia developed in one of the nonresponders at 8 weeks. Therefore, treatment had to be discontinued. Our study demonstrated single alfa-2b-interferon antitumor activity in untreated B-CLL patients with stable disease, and indicated that further trials of alfa-2b-interferon, possibly combined with chemotherapy, may be justified. PMID- 3338054 TI - Results of the treatment of children with recurrent gliomas with lomustine and vincristine. AB - Gliomas comprise over 50% of all childhood brain tumors. Treatment of recurrent childhood gliomas has been disappointing and the effectiveness of therapy has been difficult to judge because of the variable natural history of the disease. Information gathered recently has suggested that treatment with [1-(2 chloroethyl)-3-cyclohexyl-1-nitrosourea)] (CCNU) and vincristine (VCR) after radiotherapy is effective in prolonging survival in children with newly diagnosed anaplastic gliomas. The authors have used these same drugs--CCNU (100 mg/m2) and VCR (1.5 mg/m2 up to a maximum dose of 2 mg)--in 6-week cycles for a maximum of eight cycles in children with recurrent gliomas. To date, 15 patients have been treated; five patients had malignant gliomas and ten low-grade gliomas. Three children showed improvement, five had stable disease, and seven had progressive disease. Of the five patients with malignant gliomas, four progressed within two cycles of treatment and one had stable disease for 7 months on treatment and then relapsed. Seven of ten children with low-grade gliomas benefitted from treatment and six remain in continuous remission a median of 16 months after initiation of therapy. Three of these children are off all therapy 21, 30, and 30 months after treatment, respectively. Therapy was well tolerated and toxicity consisted primarily of reversible bone marrow suppression. The authors conclude that CCNU and VCR chemotherapy is effective in children with recurrent low-grade gliomas and can result in relatively long-term disease stabilization. In limited experience of the authors, it is not of benefit in children with recurrent anaplastic lesions. PMID- 3338055 TI - A pilot study of intraarterial chemotherapy with cisplatin in locally advanced head and neck cancers. AB - A prospective pilot study involving preoperative intraarterial chemotherapy with cisplatin in locally advanced oral and oropharyngeal carcinomas was initiated in March 1982. Twenty patients with TNM Stages III and IV disease underwent continuous intraarterial chemotherapy with cisplatin (90 mg/m2, at 1 mg/hour) and intravenous chemotherapy with methotrexate (50 mg/m2 X 1 dose). Arterial access was obtained by retrograde cannulation of the superficial temporal artery. One patient died of sepsis from leukopenia (mortality 5%). Catheter-related complications, most of them avoidable, totalled 30%. The total tumor response rate was 94%. With a median duration of follow-up of 14 months, the median survival of the group was not yet reached at 39 months. Eleven patients subsequently underwent definitive surgery and radiation with curative intent. When compared with matched historical controls, survival benefit was demonstrated: 60% versus 28% alive at 39 months (P = 0.015). Regional chemotherapy of cancers of the head and neck region is a feasible procedure with acceptable and avoidable morbidity. It should continue to be investigated in experimental protocols to improve patient survival. PMID- 3338056 TI - Continuous cisplatin (24-hour) and 5-fluorouracil (120-hour) infusion in recurrent head and neck squamous cell carcinoma. AB - Cisplatin and 5-fluorouracil (5-FU) has been reported to be one of the most active chemotherapeutic regimens in recurrent head and neck squamous cell carcinoma. In this study, 21 patients with recurrent head and neck squamous cell carcinoma received a combination of cisplatin given as a 100 mg/m2 continuous infusion over 24 hours and 5-FU given as a 1000 mg/m2 24-hour continuous infusion for 120 hours. Toxicity was evaluated in all patients, and response and survival were evaluated 20 patients. There were two complete remissions (10%) and three partial remissions (15%) for a major response of 25%. Overall survival for the complete responders was 79+ and 61+ weeks, respectively. Median survival for all patients was 36 weeks. Toxicity consisted of moderate to severe nausea and vomiting in 14 patients (66%), mucositis in 14 patients (66%), granulocytopenia of less than 1000/microliter in 11 patients (52%), objective peripheral neuropathy in one patient (4.7%), and nephrotoxocity in one patient (4.7%). We conclude that the efficacy of 24-hour cisplatin infusion and 120-hour 5-FU infusion in the treatment of recurrent head and neck squamous carcinoma is not superior to the efficacy of single agent trials reported in the literature. PMID- 3338057 TI - Intraperitoneal chromic phosphate therapy after second-look laparotomy for ovarian cancer. AB - Between 1973 and 1985, 118 patients in clinical remission after initial surgery and postoperative chemotherapy for epithelial ovarian carcinoma underwent second look laparotomy at the University of North Carolina. No evidence of disease (NED) was found in 57 of these patients; 43 patients received 15 mCi of radioactive chromic phosphate (32P) suspension given intraperitoneally in the immediate postoperative period. In 29 other patients, only microscopic or minimal residual disease (nodules less than 2 cm in size) was found, seven received 32P alone, ten received 32P and further chemotherapy, and 12 received chemotherapy alone. The 4 year postsecond-look survival of the patients with NED at second-look was 89% for those receiving 32P and 67% for those who had not. The respective figures for patients with minimal residual disease at second-look are 59% versus 22%. Irrespective of treatment, a group at high risk for failure after negative second look laparotomy has been identified; those with an initial International Federation of Gynecology and Obstetrics (FIGO) stage greater than I and histologic grade greater than 1. A comparison of our data with 18 previously published series, indicates that use of postsecond-look intraperitoneal 32P can improve the progression-free interval, and possibly overall survival, of patients with NED or minimal residual disease without adding significant complications. PMID- 3338058 TI - Androgen receptors in meningiomas. AB - Meningiomas have been hypothesized as being hormonally sensitive on the basis of epidemiologic, clinical, and laboratory evidence. Eight meningiomas were assayed and found to have androgen-binding protein. Three tumors were subjected to in vitro growth studies in varying concentrations of dihydrotestosterone (DHT). The growth of tumor 1 was unaltered. Tumor 2 demonstrated 9% to 10% growth (P less than 0.05) in all concentrations tested. Tumor 3 revealed an 11% stimulation, but only in the lowest concentration of DHT tested. The small quantity, saturability, and in one tumor, high binding affinity, suggest this binding protein is a receptor. The in vitro response of these meningiomas was small and was not dose related or proportionate to receptor quantity. Androgens do not appear to play as important a role as progesterone or estrogen in meningioma growth in vitro. PMID- 3338059 TI - Expression of pepsinogen II in gastric cancer. Its relationship to local invasion and lymph node metastases. AB - We have determined the prevalence of pepsinogen II (PG II) immunoreactive cells in a large series of early and advanced gastric cancers and relationships among PG II-positivity, tumor histologic type, extent of gastric wall invasion, and presence of lymph node metastases. Of the 316 cancers evaluated, 150 (47%) expressed PG II. The prevalence by histologic type was 55% in 146 glandular tumors, 43% in 83 diffuse tumors, 16% in 25 mucoid tumors, and 51% in 59 mixed type cancers. Two parietal cell cancers and one undifferentiated cancer were PG II-negative. In glandular and diffuse cancers, but not mucoid and mixed tumors, both the extent of gastric wall invasion and incidence of lymph node metastases were associated positively with PG II expression by the primary tumor. In particular, PG II-reactive cells were found significantly more often in advanced than in early diffuse cancers (P less than 0.05) and significantly more often in submucosal early cancers than in intramucosal early cancers (P less than 0.01). The prevalence of PG II expression also was higher significantly in metastatic cancers than in nonmetastatic cancers. This was true for advanced gastric cancers as a whole (P less than 0.01), advanced glandular-type cancer alone (P less than 0.01), advanced glandular- and diffuse- type cancers together (P less than 0.001), and early diffuse-type cancer (P less than 0.05). Only four (3%) of 145 cancers evaluated for pepsinogen I (PG I) were positive, and each also was positive for PG II. The results suggest that the expression of PG II by glandular and diffuse types of gastric cancer may be a marker of increased malignancy. PMID- 3338060 TI - Prognostic value of the flow cytometric DNA index in human ovarian carcinoma. AB - Flow cytometric measurements were done on 51 ovarian carcinoma specimens collected from consecutive patients in a prospective study. The ploidy status was related to the course of the disease. The tumors from 26 (52%) of 50 evaluable patients had DNA aneuploidy. Patients with diploid tumors were more often considered disease-free after initial operation (P less than 0.01). Patients with aneuploid tumors had a more aggressive course of the disease in all respects of comparison. The median survival of patients with diploid tumors was 18 months as compared to 8 months for those with aneuploid tumors (P less than 0.0005). Flow cytometric DNA measurements give important prognostic information and such analyses should be included in future clinical trials. Through the development of high-speed instrumentation they also may become feasible in routine clinical work. PMID- 3338061 TI - Evaluation of the malignant grade of thymoma by morphometric analysis. AB - To determine the histologic grade of malignancy of thymoma, the nuclear areas of epithelial cells of 42 thymomas, 14 thymic hyperplasias, and ten normal thymuses were measured by morphometry and the results were compared with the extent of disease, association with myasthenia gravis (MG), and histologic subtypes of the thymomas. The nuclei of epithelial cells of thymomas were significantly larger than those of both of thymic hyperplasias and normal thymuses (P less than 0.01). The nuclei of epithelial cells of invasive thymomas were significantly larger than those of noninvasive ones (P less than 0.001). In the noninvasive group, the nuclei of epithelial cells of thymomas associated with MG were significantly larger than those without MG (P less than 0.02), and were similar to those of invasive thymomas. These results confirm that invasive thymomas are morphometrically malignant tumors, and suggest that noninvasive thymomas associated with MG might have malignant potential. PMID- 3338062 TI - AIDS testing. PMID- 3338064 TI - Nurses as colleagues and mentors. PMID- 3338063 TI - When husbands are unemployed. PMID- 3338065 TI - A question of status. PMID- 3338066 TI - Digit reimplantation in children. PMID- 3338067 TI - Bringing Africa home. PMID- 3338068 TI - The Gynecological Teaching Associates program. PMID- 3338069 TI - [Professional pride]. PMID- 3338070 TI - [Psychiatry offends African values]. PMID- 3338071 TI - Case-control study of gestational choriocarcinoma. AB - A multicentered case-control study of 75 women who had had gestational choriocarcinoma was conducted to investigate the role of reproductive and fertility factors as well as other potential risk factors in the development of this disease. Control women, identified through random digit dialing, were individually matched to cases by year of pregnancy, age at pregnancy, and geographical proximity of residence. Choriocarcinoma risk was decreased significantly as body mass index increased (P for trend = 0.03). Cases reported low-calorie dieting significantly less frequently than controls [odds ratio estimate (OR) = 0.50, P = 0.05] and were significantly less likely to participate in regular exercise (OR = 0.38, P = 0.004). Compared to women with a heavy menstrual flow, those with light menstruation had significantly elevated risk (OR = 6.69, P = 0.01). Menarche after age 12 was also associated with elevated risk of this disease (OR = 2.89, P = 0.003). There were significantly more pairs of dizygotic twins born to cases and their first degree relatives than to controls (12 case families with 13 sets of twins versus 3 sets in control families, OR = 6.36, P = 0.009). Cases were more likely to have married more than once (OR = 13.0, P less than 0.001), and infrequent intercourse was a significant risk factor (OR for weekly or less often was 3.00, P = 0.04). Risk estimates for postmolar choriocarcinoma were not significantly different from those for all other cases. These observations and some descriptive features of the disease suggest that hormonal factors, specifically below normal estrogen levels, may be associated with a disruption of normal ovulation and thus predispose to choriocarcinoma. PMID- 3338072 TI - Oral contraceptives and cervical carcinoma in situ in Chile. AB - A case-control study of cervical carcinoma in situ was conducted in Santiago, Chile, to determine whether risk of this condition is altered by use of oral contraceptives. Responses to a standardized questionnaire were compared in 133 hospitalized cases and 254 age-matched controls selected from the same screening program through which the cases were detected. After controlling for the possible confounding influence of a variety of indices of sexual behavior, socioeconomic status, and prior cytological smears, no increase in risk was found in women who ever used oral contraceptives. No trend of increasing or decreasing risk was seen in relation to duration of use, up to more than 6 years of exposure, or with the passage of time from either initial or most recent exposure. An observed increase in risk in current users of oral contraceptives was not considered likely to represent a causal relationship. PMID- 3338073 TI - Dysplastic nevi in association with multiple primary melanoma. AB - Risk factors for multiple primary cutaneous melanoma were evaluated in a case control study. Eight cases of multiple primary melanoma were matched on sex, age, and education to 24 first primary melanoma controls. Risk factors examined in the analysis included pigmentary characteristics, history of sun exposure, and nevi. The importance of histologically dysplastic nevi (DN) and clinically atypical nevi was of particular interest. Single-factor conditional logistic regression analysis showed that first primary melanoma patients with histological DN are at increased risk for a second primary (odds ratio, 6.2; 95% confidence interval, 1.2-33.4). Patients with two or more clinically atypical nevi also have elevated risk for a second primary (odds ratio, 8.8; 95% confidence interval, 1.0-80.7). Two-factor logistic models were used to evaluate the effect of histological DN while controlling singly for all other variables as potential confounders. Odds ratios for the association of histological DN varied from 6.1 to 10.4 when adjusting singly for pigmentary and sun exposure variables. In the two-factor model that included histological and clinical DN, both variables retained marginally significant statistical association with multiple primary melanoma. These results suggest that DN is a marker of increased risk for multiple primary melanoma and suggest that melanoma patients with evidence of DN should be followed closely for the development of additional primaries. PMID- 3338074 TI - Level of HLA antigens in locoregional metastases and clinical course of the disease in patients with melanoma. AB - Immunohistochemical staining with monoclonal antibodies showed marked variations in the percentage of melanoma cells stained by anti-HLA Class I and anti-HLA Class II monoclonal antibodies among 48 locoregional metastases removed from 39 patients with malignant melanoma. On the other hand there was limited variation in the percentage of melanoma cells stained by anti-HLA antibodies in autologous locoregional metastases removed from 8 of 9 patients. In the remaining patient marked differences were found in the percentage of melanoma cells stained by anti HLA Class I antibodies in the two parts of the lymph node metastasis analyzed. Therefore this patient was not included in additional analyses to correlate the level of expression of HLA antigens with the clinical course of the disease. In all the lesions tested the percentage of melanoma cells stained by anti-HLA Class II antibodies was lower than or equal to but never higher than that stained by anti-HLA Class I antibodies. According to the level of expression of HLA Class I and Class II antigens the 38 patients could be divided into three groups: Pattern A included lesions with more than 50% of tumor cells stained by anti-HLA Class I antibodies (mean, 86.1; median, 85) and 50% or less by anti-HLA Class II antibodies (mean, 10.5; median, 5); Pattern B included lesions with 50% or less tumor cells stained by anti-HLA Class I antibodies (mean, 14.9; median, 5) and by anti-HLA Class II antibodies (mean, 4.1; median, 1); Pattern C included lesions with more than 50% tumor cells stained by anti-HLA Class I antibodies (mean, 88.8; median, 92) and by anti-HLA Class II antibodies (mean, 70.0; median, 70). The survival of 21 patients with Pattern A was significantly longer than those of 13 and 4 patients with Patterns B and C, respectively. No difference in the survival of patients in the latter two groups was found. These results suggest that HLA antigens play a role in the biology of melanoma and that analysis of the level of HLA antigens in locoregional metastases of patients with melanoma may provide clinically useful information. PMID- 3338075 TI - Inhibition of estrogen-induced renal carcinogenesis in male Syrian hamsters by tamoxifen without decrease in DNA adduct levels. AB - Estrogens have previously been shown to induce covalent DNA modifications specifically in the hamster kidney, the target organ of estrogen-inducible and dependent renal carcinoma. The DNA adducts, formed by yet unknown mechanisms, have been postulated to mediate hormonal carcinogenesis in this animal model. In an attempt to study a possible involvement of estrogen receptor mechanisms in the formation of DNA adducts, 17 beta-estradiol and the antihormone tamoxifen were concomitantly administered as s.c. implants to male Syrian hamsters. 17 beta Estradiol-treated and tamoxifen-treated animals served as positive and negative controls, respectively. The tumor incidence decreased from 100% in 17 beta estradiol-treated controls to 25% in the group receiving tamoxifen in addition to hormone. Tamoxifen-treated animals did not develop kidney tumors and did not show any detectable DNA damage. DNA adduct levels were comparable in hamsters treated with 17 beta-estradiol and 17 beta-estradiol plus tamoxifen for 5 or 7 months. In hamsters inoculated with H-301 cells, which are derived from the estrogen-induced hamster renal carcinoma and are estrogen dependent for growth, tamoxifen decreased estrogen-dependent H-301 tumor growth. However, in cell culture, neither 17 beta-estradiol nor tamoxifen influenced H-301 cell division. It was concluded that tamoxifen inhibited the growth of estrogen-induced renal carcinoma but did not interfere with tumor initiation since it did not inhibit the formation of DNA adducts. Moreover, receptor mechanisms were most probably not involved in the induction of DNA modifications by estrogens. PMID- 3338076 TI - In vitro estrogenic actions in rat and human cells of hydroxylated derivatives of D16726 (zindoxifene), an agent with known antimammary cancer activity in vivo. AB - A series of 2-phenyl-1-ethyl-3-methylindoles with or without a hydroxyl group in the para position of the phenyl ring and the 5 or 6 position of the indole nucleus were compared with 17 beta-estradiol in the stimulation of (a) prolactin production in rat pituitary cells in primary culture, (b) progesterone receptor synthesis in MCF-7 cells, and (c) proliferation of MCF-7 cells. All compounds were less active than estradiol but all derivatives including D15414, the hydroxylated metabolite of D16726 (zindoxifene, a known antitumor agent against mammary cancer) were fully estrogenic. Hydroxyl groups at the para position of the phenyl ring and 6 position of the indole nucleus conferred the highest estrogen potency [ED50 (drug concentration producing 50% of maximum activity) in all assays around 10(-10) M]. Moving or eliminating the hydroxyl on the indole ring markedly reduced the estrogen potency; however, an even more dramatic reduction in estrogenic activity was produced by removing the hydroxyl of the phenyl ring. PMID- 3338077 TI - Aerobic and hypoxic toxicity of a new class of mixed-function drugs associating nitroimidazoles and chloroethylnitrosourea in nitrosourea-sensitive (Mer-) and resistant (Mer+) human tumor cells. AB - The cytotoxicity of two series (A and B) of novel mixed-function compounds (NI CENU) combining nitroimidazole (NI) and chloroethylnitrosourea (CENU) functions were examined in Mer- HeLa-MR and Mer+ HeLa-S3 cells. Series A compounds differed from those in Series B by having a hydroxypropyl as opposed to an ethyl group linking the imidazole ring and the nitrosoureido function. Four analogues, including the imidazole and the 2-, 4-, and 5-NO2 derivatives, were evaluated in each series. Cells were exposed to the various compounds for 4 h under aerobic and hypoxic conditions, and toxicity was assessed by clonogenic assay. Corresponding analogues in Series A and B were equally toxic to HeLa-MR cells. Preferential hypoxic toxicity was observed only with the 2-NO2 derivative in either series (I-278, Series A; I-282, Series B). For either compound a dose enhancement factor of 2.4 was observed for hypoxic exposures. The Mer+ HeLa-S3 cells were considerably more resistant to the NI-CENU than were their HeLa-MR counterparts. In further contrast to the HeLa-MR data, the Series B compounds were consistently more effective against the HeLa-S3 cells than were their corresponding Series A analogues. The enhanced effectiveness of the Series B compounds in HeLa-S3 cells may be related to the fact that these compounds express carbamoylating activity whereas Series A compounds lack this property. Again only I-278 and I-282 were preferentially toxic to hypoxic cells; however, the aerobic/hypoxic differential was dramatically reduced (dose enhancement factor = 1.3) as compared to that observed with the HeLa-MR cells. The enhanced hypoxic toxicity of the 2-NO2 NI-CENUs was not due to direct hypoxic toxicity of the nitro moiety but presumably is the result of enhancement of CENU toxicity (i.e., chemosensitization). The data suggest that much lower concentrations of NI may be required to observe chemosensitization when the NI and chemotherapeutic agent are administered as a single mixed-function compound. PMID- 3338078 TI - Kinetic analysis of choriocarcinoma cell intoxication induced by ricin and ricin A chain immunotoxin. AB - The kinetics of protein synthesis inhibition was studied in the choriocarcinoma derived BeWo cell line treated with ricin and an immunotoxin (IT) constructed by linking a specific antibody to the A chain of ricin. The IT was specifically cytotoxic to BeWo and other choriocarcinoma cells. The multistep process underlying this kinetics was explored using two mathematical models where the protein synthesis-inactivation step is preceded by one or two processing rate limiting steps. Theoretical curves were computed for different concentrations of toxic reagents. Two processing steps were found necessary to predict the duration of the observed latent period before initiation of protein synthesis inhibition. With this model, a satisfactory fit was obtained. A mathematical modeling of the intoxication induced by ricin or ricin A chain IT thus requires two processing steps to account for the data observed. In addition, the data suggest that the cytoplasmic internalization of ricin is a slow process compensated by an extremely fast enzymatic inactivation of ribosomal activity. This implies that in this and similar systems, endocytosis might not be involved in the cytoplasmic internalization of the few molecules of ricin A chain responsible for cell intoxication. PMID- 3338079 TI - Contrasting actions of tamoxifen on endometrial and breast tumor growth in the athymic mouse. AB - The effects of the antiestrogen tamoxifen (TAM) on the growth of two hormone sensitive human tumors have been examined in athymic mice. The endometrial tumor, EnCa101, was stimulated to grow by TAM either alone or when combined with estradiol. This contrasted with the nonstimulation of the breast tumor, MCF-7, by TAM alone and the antagonist action of TAM on estradiol-stimulated growth of MCF 7 tumors. The individual tumor responses were observed even when the two tumor types were implanted on opposite sides of the same animal. This suggests that host metabolism of TAM does not dictate tissue response. The conclusion is supported by the finding of very similar patterns of metabolites in the two tumors after administration of [ring-3H]TAM. Tissue metabolism therefore is unlikely to be involved. Progesterone receptor levels were higher in estradiol (376 +/- 35 fmol/mg cytosol protein)- or TAM (317 +/- 37 fmol/mg cytosol protein) stimulated EnCa101 tumors than control (42 +/- 5 fmol/mg cytosol protein) and increased further with combined treatment (485 +/- 75 fmol/mg cytosol protein). Estrogen receptor levels, however, were lower in estradiol (45 +/- 11 fmol/mg cytosol protein)-treated tumors than control (92 +/- 13 fmol/mg cytosol protein) but higher than control in TAM (200 +/- 15 fmol/mg cytosol protein)-treated tumors. Tumors grown with estradiol and TAM had lower estrogen receptor levels (130 +/- 7 fmol/mg cytosol protein) than tumors grown with TAM alone. Estrogen receptor levels indicate that TAM may not be acting exactly as estradiol in the EnCa101 tumor. Overall, these findings suggest that the disparate pharmacology of TAM is a tissue-specific phenomenon. PMID- 3338080 TI - Influence of 1-beta-D-arabinofuranosylcytosine conjugates of lipids on the growth and metastasis of Lewis lung carcinoma. AB - Five different lipid conjugates of 1-beta-D-arabinofuranosylcytosine (ara-C) were tested for their therapeutic activity on the growth and metastasis of Lewis lung carcinoma (3-LL). Among 1 ester-linked lipid conjugate (Ara-CDP-L-dipalmitin), 3 1-O-alkyl-lipid conjugates (ara-CDP-D,L-PBA, ara-CDP-D,L-PCA, ara-CDP-D,L-MBA) and a thioether-lipid conjugate (ara-CDP-D,L-PTBA) ara-CDP-D,L-PTBA, ara-CDP-D,L PBA, and ara-CDP-L-dipalmitin produced the strongest tumor growth inhibition and increase of surviving animals in C57Bl6-mice bearing i.p.-implanted 3-LL. Furthermore these conjugates were superior to the parent compounds alone, or equimolar mixtures of the alkyllysophospholipid derivatives ET-18-OCH3 and ara-C. Successful therapeutic regimen consisted of 80-100 mg conjugate/kg, given i.p. daily for five consecutive days. Similar regimen injected shortly after the surgical removal of the primary tumor as adjuvant chemotherapy inhibited the metastasis of 3-LL to the lungs of the animals as demonstrated by an increase of survival time and the number of surviving animals. PMID- 3338081 TI - Biological significance of domain-oriented DNA repair in xeroderma pigmentosum cells. AB - The patterns (domain oriented versus a random location) and amounts of DNA excision repair, determined by standard density gradient techniques and sedimentation properties of partially repaired and UV-endonuclease-digested DNA in alkaline sucrose gradients, are reported for UV (254 nm)-irradiated nondividing xeroderma pigmentosum complementation group C or A (XP-C, XP-A) and normal cells. Repair synthesis in relatively UV-resistant XP-C (XP4RO) cells is domain oriented and limited (10% of normal values) while it is randomly located and not as limited in more sensitive XP-A (XP8LO) cells. Thus, greater UV resistance is associated with a very limited but domain-oriented pattern of repair. In XP-C cells, both total and domain-oriented repair syntheses, while limited, increase with UV dose and plateau at about 15-20 J/m2, as observed for normal cells. We suggest that repair in XP-C is limited at the lower UV doses (less than 15-20 J/m2) by substrate levels in specific chromatin domains and not by availability of essential enzymes for domain-oriented repair. In contrast, the XP-A strain XP8LO exhibits normal repair activities for doses up to 5 J/m2 and limited repair at higher doses, indicating that repair occurs through normal pathways that are limited by reduced availability of an essential enzyme. PMID- 3338082 TI - Glucose metabolism in drug-sensitive and drug-resistant human breast cancer cells monitored by magnetic resonance spectroscopy. AB - Glucose utilization and lactate production have been monitored as a function of time using 13C magnetic resonance spectroscopy and [13C1]-glucose with perfused wild type MCF-7 human breast cancer cells and a drug-resistant (AdrR) cell line derived from them. Compared to wild type cells, AdrR cells exhibited an enhanced (3-fold) rate of glycolysis, indicating an increased demand for ATP production. We have investigated the effects of glucose depletion and azide, an inhibitor of oxidative phosphorylation, on the levels of intracellular phosphates (Pi, ATP) and intracellular pH using 31P magnetic resonance spectroscopy and on the rates of glycolysis. In both cell lines, ATP levels and the rates of glucose utilization and lactate production were invariant in the presence of azide. ATP production, especially in AdrR cells, was highly dependent on active glucose metabolism. The results of these direct measurements confirm that these cells survive by predominantly utilizing glycolysis. Glutamate and myo-inositol were observed in 13C spectra of acid extracts of AdrR but not wild type cells. Both metabolites are potential substrates in drug detoxification. These differences in rates of glycolysis, ATP production, and the production of certain metabolites may reflect metabolic adaptations associated with the development of drug resistance. PMID- 3338083 TI - Bromine-80m-labeled estrogens: Auger electron-emitting, estrogen receptor directed ligands with potential for therapy of estrogen receptor-positive cancers. AB - To assess their possible use for estrogen receptor (ER)-directed radiotherapy of estrogen receptor-containing cancers, two estrogens were synthesized with the Auger electron-emitting nuclide bromine-80m and administered to immature female rats. Both the triphenylethylene-based estrogen, [80mBr]-2-bromo-1,1-bis(4 hydroxyphenyl)phenylethylene (Br-BHPE) and the steroidal estrogen [80mBr]17 alpha bromovinylestradiol, showed substantial diethylstilbestrol-inhibitable localization only in the estrogen target tissues, the uterus, pituitary, ovaries, and vagina and, except for the liver and intestines, generally lower concentrations in all other tissues at both 0.5 and 2 h. The [80mBr]Br-BHPE (specific activity, 8700 Ci/mmol), was shown to bind specifically to the low salt extractable ER of the rat uterus. Comparing i.p., i.v., and s.c. administration of [80mBr]BHPE the i.p. route was found to be particularly advantageous to effect maximum, DES-inhibitable concentrations of radiobromine in the ER-rich target organs in the peritoneal cavity. When the tissue distribution of the [80mBr]Br BHPE was compared with that of sodium bromide-80m, it was apparent that no substantial amounts of radiobromine were released from the bromoestrogen prior to its target tissue localization. The substantial concentration of these bromine 80m-labeled estrogens in ER-rich tissues, combined with previously reported evidence for the effective radiotoxicity of Auger electron-emitting nuclides within cell nuclei suggest a good potential for such ligands for therapy of ER positive cancers. PMID- 3338084 TI - Purification and characterization of a bindable form of mitochondrial bound hexokinase from the highly glycolytic AS-30D rat hepatoma cell line. AB - Recent studies from this laboratory have demonstrated that a form of hexokinase characteristic of rapidly growing, highly glycolytic tumor cells is bound to an outer mitochondrial membrane receptor complex containing a Mr 35,000 pore protein (D. M. Parry and P. L. Pedersen, J. Biol. Chem., 258: 10904-10912, 1983; R. A. Nakashima, et al., Biochemistry, 25: 1015-1021, 1986). In new studies reported here the specificity of this receptor complex for binding hexokinase is defined, and a purification scheme is described which leads to a homogeneous and bindable form of the tumor hexokinase. In the AS-30D hepatoma, hexokinase activity is elevated more than 100-fold relative to liver tissue. The relative increase in hexokinase activity is 8 times greater than that of any other glycolytic enzyme. Hexokinase is the only glycolytic enzyme of AS-30D cells to exhibit a mitochondrial/cytoplasmic specific activity ratio greater than 1, showing a 3.5 fold elevation in the mitochondrial fraction. Purification of hexokinase is accomplished by preferential solubilization of the mitochondrial bound enzyme with glucose-6-phosphate, followed by high-performance liquid chromatography on gel permeation and anion exchange columns. The final fraction has a specific activity of 144 units per mg of protein, with a Km for glucose of 0.13 mM and for ATP of 1.4 mM. The purified tumor enzyme migrates as a single species upon sodium dodecyl sulfate: polyacrylamide gel electrophoresis with an apparent molecular weight of 98,000. Significantly, the purified tumor enzyme retains its activity for mitochondrial binding. Additional results derived from chromatographic, polyclonal antibody, and amino acid analysis studies indicate that the predominant rat hepatoma hexokinase species is related most closely to isozymic form(s) of the enzyme commonly referred to as type II, and least related to the liver type IV isozyme (glucokinase). PMID- 3338085 TI - Binding of gastrin(17) to human gastric carcinoma cell lines. AB - The hormone gastrin stimulates acid secretion by gastric parietal cells and acts as a growth factor for the gastric mucosa. Gastrin receptors with dissociation constants of approximately 0.5 nM have been detected on isolated gastric parietal cells, and on some cell lines derived from colon carcinomas. We now report that gastrin is also bound by five cell lines derived from human gastric carcinomas, but that the affinities of these lines for gastrin range from 0.2 to 1.3 microM. Cholecystokinin8 binds to the cell line Okajima with an affinity similar to gastrin17, while shorter gastrin analogues bind with reduced affinity. Binding of gastrin is unaffected by acetylcholine, histamine, or a number of other hormones with the exception of insulin which inhibits binding with an IC50 value of 0.5 microM. The ability to bind gastrin with affinities in the microM range appears to be a property widespread among other tumor cell lines. PMID- 3338087 TI - Transplantation studies of a putative lymphosarcoma of Xenopus. AB - The fate of the putative transplantable Xenopus lymphosarcoma (M. Balls, Cancer Res., 22: 1142-1154, 1962) was studied under three experimental conditions: (a) xenotransplantation, i.e., transplantation of live "tumor" tissue between adults of Xenopus borealis and X. laevis; (b) inoculation of live "tumor" cells from X. borealis into the blastocoele of X. laevis embryos; and (c) transplantation of "tumor" tissue into recipient adults immunologically unresponsive to the donor tissue antigens. This condition is fulfilled by using X. laevis-X. gilli (LG) hybrids [H.R. Kobel and L. Du Pasquier. In: J.B. Solomon and J.D. Horton (eds.), Developmental Immunology, pp. 229-306. The Netherlands: Elsevier/North-Holland Biomedical Press, 1977] as donors, and triploid X. laevis-X. gilli and X. borealis (LGB) hybrids [C.H. Thiebaud, Dev. Biol., 98: 245-249, 1983] as recipients. In all transplantation experiments, donor and recipient cells could be unambiguously distinguished upon quinacrine staining that yields typical nuclear patterns, for instance bright patchiness in X. borealis, visible also in LGB cells. The results of xenotransplantation between X. borealis and X. laevis indicated that all developing "tumors" were composed of the recipient cell phenotype. The inoculation of live "tumor" cells from X. borealis "tumor" into the blastocoele of X. laevis embryos resulted in "tumor" formation in the recipient tadpoles and in metamorphosed animals. The cell constituting these "tumors" all were of recipient, X. laevis cell phenotype. Finally, "tumor" tissues from LG clones transplanted into LGB hosts were replaced by "tumors" formed of cells with recipient, LGB phenotype. These experiments indicate that this Xenopus tumor-like growth is a transmissible and not a transplantable disorder. PMID- 3338086 TI - Synergistic cell inactivation of human NHIK 3025 cells by cinnamaldehyde in combination with cis-diamminedichloroplatinum(II). AB - The cell-inactivating effect induced by cinnamaldehyde in combination with cis diamminedichloroplatinum(II) (cis-DDP) on human NHIK 3025 cells in culture was investigated. Cell inactivation was measured as a loss in the ability of single cells to give rise to macroscopic colonies following drug treatment. Although 2 h treatment of asynchronous cells with 0.3 mM cinnamaldehyde alone induced little cell inactivation, the drug combination of 0.3 mM cinnamaldehyde and 10 microM cis-DDP resulted in synergistic cell inactivation. Cinnamaldehyde potentiated the cell-inactivating effect of cis-DDP by a dose-modifying factor of 1.8. Drug synergism was found to occur only when cinnamaldehyde and cis-DDP were given in simultaneous combination. Treatment of synchronized cells demonstrated that cinnamaldehyde potentiated the inactivating effect of cis-DDP in all phases of the cell cycle. Cinnamic acid and cinnamyl alcohol were found to have no synergistic or potentiating effect on cell survival following treatment of cells with cis-DDP, thus indicating the importance of an aldehyde moiety for drug synergism. PMID- 3338088 TI - Mycobacterium-induced infectious granuloma in Xenopus: histopathology and transmissibility. AB - The acid-fast bacteria present in the transmissible putative Xenopus lymphosarcoma (px1) (M. Balls, Cancer Res., 22: 1142-1154, 1962) were isolated and identified as Mycobacterium marinum. M. marinum induces an infectious granuloma in Xenopus which is histopathologically indistinguishable from Xenopus "lymphosarcoma" (px1). It had been reported that the filtrate (0.22-micron pore size) and the supernate of ultracentrifugation (20,000 x g) of the pxl tissue homogenate were bacteria free and could transmit the disease (R.H. Clothier and M. Balls, Oncology, 28: 445-457, 1973; R.H. Clothier and M. Balls, Oncology, 28: 458-480, 1973). Both features, however, also correspond to the transmission of M. marinum-induced granuloma. The granuloma induced by the ultrafiltrate of granulomatous tissue homogenate may be due to the granulomatogenic component of the bacteria-containing tissue, since no bacteria were detected in such filtrate. The 100,000 x g centrifugation supernate of the same homogenate, however, contains bacteria which induce granuloma. Since no other feature of pxl corresponds to neoplasia, it is concluded that as diagnosed by Dawe [C.J. Dawe, Natl. Cancer Inst. Monogr., 32: 7-28, 1969; C.J. Dawe. In: M. Mizell (ed.), Recent Results in Cancer Research, pp. 429-440. New York: Springer-Verlag, 1969; C.J. Dawe. In: R.M. Dutcher (ed.), Comparative Leukemia Research. Bibliotheca Haematologica pp. 634-637. New York: Karger, 1970], this spontaneous abnormal growth of Xenopus actually is an infectious granuloma. PMID- 3338089 TI - Modification of cell surface carbohydrates and invasive behavior by an alkyl lysophospholipid. AB - The effect of the alkyl lysophospholipid racemic-1-O-octadecyl-2-O-methyl glycero 3-phosphocholine on the expression of cell surface carbohydrates of four matched pairs of normal and malignant cells was studied using chromatographic techniques. After treatment with alkyl lysophospholipid, glycopeptides proteolytically derived from normal and malignant cells displayed a shift in the size distribution profiles obtained by gel filtration. These drug-induced changes in molecular weight distribution were expressed most strongly in untransformed cells and resembled the carbohydrate alterations found after their malignant transformation. Desialylation abolished the effect of alkyl lysophospholipid, thus suggesting an increased amount of sialic acid in the surface carbohydrates of drug-treated cells. Chromatography of glycopeptides on concanavalin A Sepharose, Ricinus communis agglutinin I-agarose, and Bio-Gel P-4 columns excluded a higher degree of branching but suggested addition of extra terminal sialic acid residues as the major cause of the observed alterations. Alkyl lysophospholipid stimulated glycoprotein sialylation of normal cells to the level observed in malignant cells, thus inducing a "malignant-like" surface phenotype. The drug-induced carbohydrate changes in normal chick heart tissue prevented its being invaded by tumor cells when tested in an organotypic assay. The alkyl lysophospholipid thus appears to modulate in a nontoxic fashion the expression of surface molecules implicated in various cellular interactions including invasiveness. PMID- 3338090 TI - Chromosomal analysis of sixteen human rhabdomyosarcomas. AB - Chromosomal analysis of 16 rhabdomyosarcomas was done from four primary tumors and from 12 tumors after nude mouse passage. Seven tumors were alveolar; four of these had t(2;13)(q37;q14) and in two tumors it was the only structural abnormality. The other three alveolar tumors were near tetraploid with marker chromosomes and double minutes. In the nine embryonal tumors studied, one had a normal karyotype, and eight were abnormal. Although the eight tumors had no common structural abnormality, trisomy 2 was present in all. PMID- 3338091 TI - Irradiation-induced marker chromosomes in a metastasizing murine tumor. AB - We have used irradiation to induce marker chromosome formation in a metastasizing murine tumor with a stable karyotype. The induced recombinant chromosomes then served to determine whether metastases were of clonal or multicellular origin. Cumulative data were obtained from four series of experiments on spontaneous metastases originating from tumors grown from irradiated cells; 20 of these metastases expressed unique chromosomal alterations consistent with a clonal origin. The majority of metastasis-derived cell populations remain stable with respect to their marker chromosomes in culture as well as in successive animal transplantation. In several instances, however, chromosomal instability was sufficient to obscure the cellular origins of individual metastases. A few metastases showed mixed chromosomal patterns initially that were consistent with multicellular origin, but repeat examinations have revealed a chromosomal instability which persisted during propagation in culture. The frequency of chromosomal recombinants in metastases from the combined series was sufficient to suggest biological and statistical significance. The morphology of recombinants was not associated with radiation dose but appeared as an apparently random response of the tumor population in different experiments. Analysis of chromosomal markers by banding techniques was performed to determine if specific chromosomes or chromosomal sites were associated with tumor cells from metastatic foci (a host-selected subpopulation with a metastatic phenotype). Our results did not reveal preferential involvement of whole chromosomes or intrachromosomal sites in recombinant formation. PMID- 3338092 TI - Killing of human tumor cell lines by human monocytes and murine monoclonal antibodies. AB - We evaluated the capacity of freshly isolated blood monocytes to mediate antibody dependent cellular-mediated cytotoxicity (ADCC) in cooperation with murine anti tumor monoclonal antibodies (MAbs). Blood monocytes isolated from most donors by adherence selection to fibronectin-coated plastic surfaces and subsequently depleted of natural killer/killer (NK/K) cells exhibited significant ADCC activity against tumor cell lines in combination with an IgG3 antitumor MAb (BR55 2). However, significant variation in ADCC competence was observed among donors. Culture parameters influencing monocyte ADCC activity were evaluated and optimized. The influence of MAb isotype on ADCC capacity of anti-tumor MAbs was also evaluated using anti-tumor class-switch variant hybridoma proteins and a panel of anti-tumor MAbs. MAbs of the IgG2a and IgG3 subclasses exhibited high ADCC potential, whereas MAbs of the IgG2b subclass exhibited no ADCC activity. One of two IgG1 MAbs tested exhibited high ADCC activity with monocyte effectors. The role of monocytes or macrophages in tumor remission of cancer patients undergoing MAb immunotherapy is not known. However, correlative studies of monocyte ADCC capacity and responsiveness of cancer patients to MAb immunotherapy may help to establish the role of these effectors in MAb-mediated tumor remissions. PMID- 3338093 TI - Induction of cell-mediated cytotoxicity by shark 19S IgM. AB - Plasma from unimmunized nurse sharks can mediate a reaction similar to antibody dependent cell-mediated cytotoxicity (ADCC). Normal shark plasma contains numerous natural antibodies reactive with a variety of antigens, including the target employed. Adsorption of plasma with target cells removed a significant amount of activity, suggesting involvement of antibody. Purified 19s IgM was shown to be a component of shark plasma capable of inducing cytotoxicity. These cytotoxic reactions differ from observations in homeothermic vertebrates in that shark immunoglobulin appears to bind more avidly to the effector cells than to the targets. The effector leukocytes are glass adherent, but not susceptible to carbonyl iron treatment, which clearly separates them from the phagocytic effectors of spontaneous cytotoxicity. Thus, the shark possesses leukocytes with the capability of mediating an ADCC-like reaction. These leukocytes, in concert with those mediating spontaneous cytotoxicity, could provide the shark with an effective immunosurveillance system. These data also indicate that ADCC mechanisms, with IgM as the primary effector molecule, appeared early in evolution. PMID- 3338094 TI - Cell-mediated responses and protection elicited by a carbohydrate-lipid containing fraction extracted from Leishmania major promastigotes. AB - Carbohydrate-lipid-containing fractions (CLF) extracted from Leishmania major promastigotes and recognized by sera from immune but not from normal human donors were evaluated for their capacity to elicit cell-mediated responses. It was found that one of these fractions, CLF-1, stimulated the in vitro response of lymphocytes from immune but not from normal human donors. A similarly extracted fraction from L. donovani parasites also elicited an in vitro response by cells from donors immune to L. major. The response was mediated by antigen-presenting cells, and specific Leu 3+ Leu 2- T cells from a human T-cell line responded to the antigen. In vivo, the CLF-1 elicited delayed-type hypersensitivity (DTH) response in L. major-immunized C3H mice, which was comparable to the DTH response elicited by freeze-thawed and sonicated L. major promastigotes. C3H mice were vaccinated with CLF-1 prior to challenge with live L. major promastigotes. Mice vaccinated with CLF-1-containing liposomes showed a significant degree of protection to challenge. These results suggest that the carbohydrate-lipid containing fraction described here may represent a functional antigenic entity from Leishmania parasites. PMID- 3338095 TI - Host H-2 genotype regulates the metastatic ability of H-2-associated variants of B16 melanoma: defense systems screening for absence of self H-2 components by natural killer cells and host-associated homing barrier. AB - The mechanisms of host H-2-associated resistance against metastasis of tumor cells were evaluated in relation to the H-2 phenotype of tumor cells. We used H-2 heterozygous H-2a/b and H-2d/b, and H-2 homozygous H-2b/b hosts, and H-2 associated variant lines of B16 cells (H-2b+, H-2b-). In H-2b/b hosts, H-2+ cells were highly metastatic in vivo, and were resistant to host NK effectors in vitro. Therefore, H-2a/b and H-2d/b hosts showed resistance to metastasis of H-2+ cells and their effectors showed killing activity to these cells in vitro. Though the host resistance was reduced by anti-asialo GM1 serum treatment, these hosts continued to demonstrate a considerable resistance against early survival and metastasis of the B16 cells. To evaluate this natural resistance, aside from the NK system, radiation bone marrow chimeras of F1-parental combinations were used. The data suggest that host MHC-associated resistance involves not only the NK defense system but also the host environmental resistance. Both exert resistance by recognizing the H-2 mismatch in relation to the host. PMID- 3338097 TI - Characterization of Langmuir-Blodgett films of 1,2-dipalmitoyl-sn-glycero-3 phosphatidylcholine and 1-palmitoyl-2-[10-(pyren-1-yl)decanoyl]-sn-glycero-3 phosphat idylcholine by FTIR-ATR. AB - Monomolecular films of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1-palmitoyl-2-[10-(pyren-1-yl)decanoyl]-sn-glycero-3-phosphatidylc holine (PPDPC) were transferred from an air/water interface onto a germanium attenuated total reflection crystal by the Langmuir-Blodgett (LB) technique. The assemblies were thereafter investigated by Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy. To determine the molecular organization in the deposited layers we monitored the CH2 and C = O stretching and the CH2 bending regions of the infrared spectra of these lipids in detail. Using Fourier self-deconvolution technique, the carbonyl stretching mode was resolved into two models corresponding to the conformational differences in the ester linkages of the phospholipid sn-1 and sn-2 acyl chains. By varying the temperature of the subphase and using different surface pressures, we were able to transfer different conformational states of DPPC onto a germanium ATR crystal. Deposition of DPPC at 40 mN m-1 and at 15 degrees C or at 20 mN m-1 and at 35 degrees C results in LB-assemblies in ordered or disordered states, respectively, as judged by the IR spectra. These structures in LB films correspond to the state of DPPC in liposomes below and above the temperature of the order-disorder phase transition. Irrespective of the surface pressure and subphase temperature used during the deposition, an ordering process was found in DPPC films when the number of the transferred layers was increased from one to five. The pyrene labelled phosphatidylcholine analogue, PPDPC, behaved differently from DPPC. In the case where one to three layers of PPDPC transferred at 35 mN m-1 and at 20 degrees C only conformational structures resembling those in fully hydrated liposomes above the main transition temperature were observed. PMID- 3338096 TI - Macrophage cell cycling: influence of proliferative state on the antibody mediated activities of rat resident peritoneal macrophages. AB - Countercurrent centrifugal elutriation (CCE) was used to isolate fractions of rat resident peritoneal macrophages that were enriched in different phases of the cell cycle. The purpose was to assess the influence of the proliferative status of these cells on their antibody-mediated phagocytic activity. Autoradiographic analysis of the resident peritoneal cell population isolated 1 hr after an intravenous injection of [3H] thymidine showed that about 3% of the macrophages were in S-phase of the cell cycle. CCE yielded fractions of macrophages in which the proportions of S-phase cells ranged from 0% to about 10%. Results of flow cytometric analysis of propidium iodine-stained cells were consistent with the autoradiographic findings. Essentially all of the macrophages in the CCE fractions ingested antibody-coated particles, but there were marked differences in phagocytic capacity and in expression of Fc-receptors among discrete groups of cells. CCE fractions with the smallest cells and no S-phase macrophages ingested approximately six- to eightfold fewer particles than did macrophages from CCE fractions with the largest cells and enriched in S-phase macrophages. Similarly, smaller macrophages bound fewer antibody-coated particles than did larger macrophages. These results, which are identical to those previously reported for murine macrophage cell lines, show that the number of Fc-receptors and the phagocytic capacity of cycling resident peritoneal macrophages increase as the cells progress from G1 to G2. Thus, the proliferative state of macrophages does not determine whether they are phagocytic but rather their phagocytic capacity. PMID- 3338098 TI - Fourier transform infrared study on the thermotropic behaviour of fully hydrated 1-palmitoyl-2-[10-(pyren-1-y) decanoyl]-sn-glycero-3-phosphatidylcholine. AB - Fourier transform infrared (FTIR) spectroscopy was used to study the thermotropic behaviour of fully hydrated 1-palmitoyl-2-[10-(pyren-1-yl)-decanoyl]-sn-glycero-3 phosphatidyl choline (PPDPC) in the temperature range of 3-30 degrees C. Several changes in the spectral features of PPDPC were observed. Major alterations analogous to the gel-to-liquid crystalline phase transition of saturated phosphatidylcholines were evident at approximately 16 degrees C in both the wavenumbers and the halfbandwidths of five different vibrational modes of PPDPC, viz. asymmetric and symmetric CH2 stretching, C = O stretching, and CH2 bending. Also the pyrene ring deformation mode changed at this temperature. Using Fourier self-deconvolution technique we resolved the carbonyl stretching mode into two bands at approx. 1741 and 1726 cm-1. These bands are due to conformational differences in the ester linkages of the two acyl chains, and are further assigned on the basis of literature data to the sn-1 and sn-2 carbonyl groups, respectively. The ratio of the relative intensities of these two bands is shown to depend on the phase state of the phospholipid. PMID- 3338100 TI - X-ray diffraction studies of lipid phase transitions in cholesterol-rich membranes at sub-zero temperatures. AB - In X-ray diffraction studies of hydrated (greater than 60%) cholesterol/dioleoylphosphatidylcholine mixtures the lipid packing band showed an abrupt transition from liquid crystal-type to gel-type position and definition at a temperature which decreased progressively to almost -50 degrees C as the proportion of cholesterol was increased to a saturation level of about 50 mol%. Plots of transition temperature against composition (mol% cholesterol) and of peak position against composition provided evidence of a significant change in phospholipid configuration at about 20 mol% cholesterol. However, the data overall suggested a uniform dispersion of the cholesterol molecules in the phospholipid bilayer at all concentrations up to the saturation point. Parallel studies of hydrated lipid extract of erythrocyte membranes and of several cholesterol-rich membrane preparations showed a similar overall change from liquid crystal-type packing at +20 degrees C to a gel-type packing at -30 degrees C to -40 degrees C but without displaying a defined transition temperature. PMID- 3338099 TI - Effect of sodium octanoate and sodium perfluorooctanoate on gel-to-liquid crystalline phase transition of dipalmitoylphosphatidylcholine vesicle membrane. AB - The gel-to-liquid-crystalline phase transition of dipalmitoylphosphatidylcholine (DPPC) vesicle membrane was measured in the presence of sodium octanoate (SO) (pH 3 and 10) and sodium perfluorooctanoate (SPFO) (pH uncontrolled) by monitoring the scattered light intensity of the vesicle suspension. The phase transition temperature, Tm, decreased linearly with the concentration of added SO within the measured concentration range; the uncharged form of SO (pH 3) was much more effective for the depression of Tm than the charged form (pH 10). On the other hand, with increasing SPFO concentration, levelling off of Tm was observed after depression at an initial stage. From the depression of Tm, the partition coefficients, K, of these surfactants between bulk solution and DPPC vesicle membrane were estimated and compared with those obtained previously for other surfactant systems. The value of K for charged SO fell on the straight line of log K vs. Nc plot for anionic surfactants, where Nc is the carbon number of the hydrocarbon chain of surfactants, whereas K for uncharged SO showed a large positive deviation from the straight line of the plot for non-ionic surfactants. The latter suggested that some specific interaction, presumably hydrogen bond formation, may act between the protonated carboxyl group of SO and the lipid head group. The K value estimated for SPFO was much larger than that for charged SO. This difference in the affinity for the lipid bilayer between fluorocarbon surfactant and hydrocarbon surfactant may be attributed to the difference in their hydrophobicity. PMID- 3338101 TI - Preparation of passive bilayer liposomes. AB - In studies of in-membrane molecular interactions, need may arise for a matrix that cannot itself interact, except hydrophobically, with the reactants. Such a bilayer matrix should, ideally, consist of only a hydrophobic zone without ionic outer layers and without hydrogen belts (the membrane strata containing CO and OH groups). However, because of the necessity of anchoring the bilayer to its aqueous surroundings, there must be polar substituents. Hydrophilic ether groups in the form of polyoxyethylenes can provide nearly sufficient anchoring and yet not confer unwanted reactivity to the membrane since they are only very weak H bond acceptors. The stability of the bilayer is ensured by the presence of a few percent of an amphiphile (which may be the substrate to be studied, e.g. a phospholipid) or by a free polyethylene hydroxy group far remote from the original hydrogen belt region. Our most impermeable liposomes consisted of O methylcholesterol/O-methoxyethoxyethoxyethylcholesterol; the most readily prepared liposomes were made from O-methylcholesterol and hydroxy(ethoxy)4dodecane (Brij 30) or Triton. PMID- 3338102 TI - Strain difference in rat renal microsomal epoxide hydrolase elevation after mercuric chloride treatment. AB - Administration of the nephrotoxicant mercuric chloride (HgCl2) was found to increase microsomal epoxide hydrolase (EH) activity in the kidneys of Fischer 344 (F344) and Sprague-Dawley (SD) rats, but the increases observed were 2- to 4-fold greater in SD rats than in F344 rats. This study was designed to characterize HgCl2-mediated increases in renal EH activity, and to investigate possible biochemical mechanisms underlying the strain difference. In male SD rats killed 24 h after the last of three daily i.p. injections of HgCl2 (0.1-1 mg/kg), increases in renal EH activity were dose dependent, reaching a maximum of 550% of control. Renal EH activities in identically treated F344 rats were enhanced only to 200% of control values, however, the extent of nephrotoxicity was similar in both strains. Following a single HgCl2 treatment (1 mg/kg), maximal increases in renal EH activities were observed in SD rats (450% of control) at 3 days, and in F344 rats (225%) at 1-2 days. Hepatic glutathione (GSH) concentrations were unaffected by HgCl2 treatment, whereas renal GSH was slightly elevated in both strains. Hepatic metallothionein (MT) concentrations were increased at 1 day to 300% and 400% of control in F344 and SD rats, respectively. Maximal renal MT concentrations were observed at 2 and 3 days in F344 (300% of control) and SD (225%) rats, respectively. Pretreatment with Zn(OAc)2, a potent inducer of renal and hepatic MT, reduced the nephrotoxicity of HgCl2, but did not alter HgCl2 mediated renal EH increases in either strain. In addition, possible strain differences in 203HgCl2 distribution were assessed, but 203Hg distribution was similar in both strains. These studies have demonstrated that renal EH activity is induced by HgCl2, and that there is a strain difference in this response. Differences in MT, GSH and organ distribution of Hg do not account for the strain difference. The possibility remains that other, yet to be defined, protection pathways may exist. Alternatively, renal EH may be differentially regulated between the two strains. PMID- 3338103 TI - Expression of insulin-like growth factor I (IGF-I) and IGF-II mRNA during hepatic development, proliferation and carcinogenesis in the rat. AB - Insulin-like growth factor I (IGF-I) and IGF-II are peptides that presumably are required for normal fetal and postpubertal growth. The production of IGFs is developmentally regulated and the liver appears to be a major site of production. By analysing mRNA levels for IGF-I and IGF-II in the rat liver we have attempted to further study the expression of these growth factors during development and regeneration as well as during the course of hepatic carcinogenesis. Fetal livers are characterized by a high level of IGF-II mRNA and a low level of IGF-I mRNA, while in adult livers the opposite situations occur, i.e. a high level of IGF-I mRNA and a non-measurable level of IGF-II mRNA. During the course of experimentally induced hepatic cancer, IGF-I mRNA was consistently reduced and in a majority of cancers analysed (6/9) IGF-II mRNA was increased, i.e. a fetal type of IGF expression can be switched on in some experimentally induced hepatocellular carcinomas. The onset of IGF-II production during hepatic carcinogenesis appears to be a late phenomenon since liver nodules, preceding the development of hepatocellular cancer, were found not to contain IGF-II mRNA. Furthermore, during hepatic regeneration following partial hepatectomy no marked change in IGF-I or IGF-II mRNA levels was noted. The above results suggest that the fetal growth factor IGF-II could have a role in hepatic cancer. PMID- 3338104 TI - Reciprocal relationship between development of glutathione S-transferase positive liver foci and proliferation of surrounding hepatocytes in rats. AB - The effects of 2-acetylaminofluorene (2-AAF), phenobarbital (PB) and butylated hydroxyanisole (BHA) on the competitive proliferation of glutathione S transferase (GST-P) positive liver cell foci induced by diethylnitrosamine (DEN) and surrounding hepatocytes were studied. Rats were given a single i.p. injection of 200 mg/kg body wt of DEN and from 2 weeks later were given a diet containing 0.02% 2-AAF (group 1), 0.05% PB (group 2), 2.0% BHA (group 3), or no supplement (group 4) for 6 weeks. All rats were subjected to partial hepatectomy (PH) at the end of week 3. Animals from each group were killed 1, 2, 3 or 4 days or 1, 2, 3 or 5 weeks after PH. Sequential changes in cellular proliferations after PH were investigated by immunohistochemical staining for GST-P and autoradiography of [3H]thymidine. The development of GST-P positive foci was enhanced strongly by 2 AAF and slightly by PB and was inhibited by BHA. In the group treated with 2-AAF, proliferation of hepatocytes adjacent to foci was almost completely inhibited [labelling index (LI) = 0.4-1.5], but GST-P positive foci cells had a high LI (16.2-26.1) 1 week after PH. In the group treated with PB, proliferation of surrounding hepatocytes was slightly inhibited (LI one day after PH = 16.0) compared with that of control (LI = 24.2), but proliferation of cells in GST-P positive foci was not inhibited (LI one day after PH = 11.3; control value = 11.0). BHA retarded recovery of the LI (LI 4 days after PH = 8.1; control value, 4.0) and did not inhibit proliferation of surrounding hepatocytes. These results indicated an inverse relationship between the development of GST-P positive foci and proliferation of surrounding hepatocytes. PMID- 3338105 TI - Differential metabolic response of rat liver, kidney and spleen to ethionine exposure. S-adenosylamino acids, homocysteine and reduced glutathione in tissues. AB - Intraperitoneal injection of ethionine to male rats for up to 12 days caused a pronounced fall in S-adenosylmethionine (AdoMet) in liver, but did not or only slightly affect AdoMet in kidney and spleen. Liver and to a lesser degree kidney showed a dose-dependent, massive accumulation of the metabolic product, S adenosylethionine (AdoEth), and this metabolic response was most pronounced within the first days of exposure. Trace amounts of AdoEth was demonstrated in the spleen. Both S-adenosylhomocysteine (AdoHcy) and homocysteine (Hcy) in the liver were markedly increased in a dose- and time-dependent manner. There was a moderate increase in Hcy content in spleen and kidney, whereas the AdoHcy levels in these tissues were not affected. The amount of reduced glutathione (GSH) was significantly increased in liver and kidney. This response in liver was evident within 2 days of ethionine exposure and then leveled off whereas there was a gradual increase in GSH in kidney. The GSH content in spleen was unaltered. In addition to a massive build-up of AdoEth, the unique features of the metabolic response of the liver are a pronounced decrease in the AdoMet/AdoHcy ratio (from 15 to 2) associated with an elevated Hcy content and a rapid increase in the amount of GSH. The possibility that the metabolic response of the liver could be assigned to the existence of isozymes or metabolic pathways unique to hepatic cells is discussed. PMID- 3338106 TI - Persistence of benzo[a]pyrene and 7,8-dihydro-7,8-dihydroxybenzo[a] pyrene in Fischer 344 rats: time distribution of total metabolites in blood, urine and feces. AB - A comparison of the rates of elimination of [3H]benzo[a] pyrene (BaP) and 7,8 dihydro-7,8-diol-[3H]benzo[a]pyrene (BPD), after subcutaneous injection into Fischer 344 rats, shows they are both eliminated at about the same rates and with the same pattern over at least 7 days post-exposure. The end-rate of combined urinary and fecal excretion was approximately 40 nmol/day. About 20% of the injected BaP and approximately 3% of the injected BPD remained at the site of injection for at least 9 days. The remainder was distributed throughout the animal. If the rate of excretion continued at the observed steady-state rates, the BaP and BPD could persist for up to 40 days for each milligram of injected substance. The concentration of excretion products were highest during day 1 and day 2 following exposure, decreased exponentially to a concentration of approximately 0.5 microM (mixed metabolites) by day 5 following exposure, and then continued to be excreted at that rate. Feces contained the highest total amounts of radioactivity, which were approximately 2- to 4-fold higher than the amounts in urine and approximately 15- to 50-fold higher than in total blood. The conversion of organic 3H to 3H2O during the experimental period indicates that whole-body phenol(quinone) formation was significant for BaP metabolism, but was much less for BPD metabolism. When BaP was injected, both blood and urine contained water-soluble, volatile tritium counts (3H2O). Injection of BPD resulted in volatile 3H2O in urine but not in blood. The persistence of BaP and BPD metabolites in skin, blood, urine and feces compartments indicates there is a substantial reservoir of the chemical(s) that could be used to replenish repaired or discarded DNA adducts. PMID- 3338107 TI - Active oxygen induced DNA strand breakage and poly ADP-ribosylation in promotable and non-promotable JB6 mouse epidermal cells. AB - The evidence is convincing that oxidants and agents which induce a cellular pro oxidant state can act as carcinogens, in particular as promoters and progressors. Importantly, infiltrated phagocytes represent a source of oxidants in inflamed tissues. We have studied the mechanism of the promotional action of active oxygen (AO) in mouse epidermal cells JB6 by comparing the non-promotable clone 30 to the promotable clone 41. In order to mimick AO released by phagocytes we used xanthine/xanthine oxidase as a source of extracellular superoxide and hydrogen peroxide. We found that AO stimulated the growth only of promotable clone 41 after an initial period of moderate inhibition while it was strongly cytostatic for non-promotable clone 30. Reasons for the higher cytostatic effect of AO on the non-promotable clone 30 were discovered when we measured DNA strand breakage and poly ADP-ribosylation of chromosomal proteins. At equal doses AO induced 4-5 times more DNA breaks in clone 30 in reactions which required iron--and probably also calcium--ions. The higher amount of DNA breakage in clone 30 was reflected in a higher extent of poly ADP-ribosylation. Excessive DNA breakage and poly ADP ribosylation which causes the depletion of NAD and ATP may be responsible for the strong cytostatic effect of AO in clone 30. We conclude that differential resistance to the cytostatic/cytotoxic effect of AO in part determines the promotability of mouse epidermal cells JB6. PMID- 3338108 TI - Metabolism of K-region derivatives of 1-nitropyrene by rat liver in vitro. AB - The metabolism of K-region derivatives of 1-nitropyrene was studied in order to provide insight into factors that may contribute to their mutagenic activities and to obtain information on unknown metabolites of 1-nitropyrene. Using 9000 g supernatant from livers of Aroclor-treated rats, 1-nitro-pyrene-4,5-diol, a mutagenic metabolite of 1-nitropyrene, was metabolized to 1-aminopyrene-4,5-diol, a mixture of 1-nitropyrene-4,5,9,10-tetraols, 1-amino-4,5-pyrenedione and 1-nitro 4,5-pyrenedione. 1-Nitro-5H-phenanthro[4,5-bcd]pyran-5-one, a highly mutagenic lactone, was not detected. The metabolism of 1-nitro-4,5-pyrenedione yielded only 1-amino-4,5-pyrenedione; the lactone was not observed. No metabolites were detected when the lactone was incubated under conditions identical to those employed for 1-nitro-4,5-diol and 1-nitro-4,5-pyrenedione. Upon re-examination of the metabolism of 1-nitropyrene, we were able to detect 1-nitropyrene-4,5,9,10 tetraol, 1-amino-4,5-pyrenedione and 1-nitro-4,5-pyrenedione as minor metabolites in addition to the major metabolites reported previously. The results of this study, combined with the mutagenicity data for the K-region derivatives of 1 nitropyrene, suggest that nitroreduction of 1-nitropyrene-4,5-diol and 1-nitro 4,5-pyrenedione to the corresponding hydroxylamines is an important pathway for their metabolic activation in Salmonella typhimurium and their metabolic activation in Salmonella typhimurium and possibly in mammalian systems. PMID- 3338110 TI - Synergistic effects on the initiation of rat liver tumors by trans-4 acetylaminostilbene and 2-acetylaminofluorene, studied at the level of DNA adduct formation. AB - Both trans-4-acetylaminostilbene (AAS) and 2-acetylaminofluorene (AAF) exert tumor-initiating activity in rat liver when administered in the initiation phase of an initiation-promotion experiment. The effects are more than additive when the compounds are sequentially combined in the initiation phase of such an experiment, and this synergism is more pronounced when AAS is given first, followed by AAF, than vice versa. In order to determine the role of target DNA dose, [3H]AAS and [14C]AAF were administered to female Wistar rats adhering to the protocol of the initiation phase of the above-mentioned experiment and the following parameters measured at the end of this phase: total radioactivity in tissues, binding to DNA, RNA and proteins in liver, adduct pattern in liver DNA and RNA. In neither combination were these parameters significantly different from those in the appropriate controls in which only one of the compounds was administered. This result indicates that combining the substances did not alter the pharmacokinetics of the individual compounds and that the target dose is additive. This suggests that effects unrelated to DNA binding, possibly promoting effects, may cause the more than additive generation of preneoplastic lesions in rat liver. PMID- 3338109 TI - Liver cell proliferation and incidence of hepatocellular carcinomas in rats fed consecutively a choline-devoid and a choline-supplemented diet. AB - A group-set of male Fischer 344 rats was kept on a choline-devoid (CD) diet for 3, 6, 9, 12 or 16 months. A second set was fed the same diet for 3, 6 and 9 months, followed by a control, choline-supplemented diet for 3 months. A third set was fed the CD diet for 0, 3, 6, 9 and 12 months and the control diet for the duration (16 months) of the experiment. [3H]Thymidine was injected into some of the animals to assess the extent of liver cell proliferation. In the latter animals, liver triacylglycerols were also determined as an index of the hepatonecrogenic action of a CD diet. Foci of enzyme-altered hepatocytes were detected histochemically and the presence of tumors was established histologically. Cell proliferation and triacylglycerols were both high after 3 months and declined steadily as the length of CD diet feeding increased. Upon subsequent feeding with the control diet, triacylglycerols promptly cleared from the liver, while cell proliferation remained at reduced but still relatively high levels for at least 3 months. Increasing but small numbers of foci of enzyme altered hepatocytes were detected in some of the rats under experimentation for 6 months or longer. The incidence of hepatocellular carcinomas was 13, 27, 33 and 73% respectively in rats fed the CD diet for 3, 6, 9 or 12 months and the control diet for the duration of the experiment. On the other hand, only 26% of the rats fed exclusively the CD diet for 16 months developed carcinomas. The results were taken as evidence that: (i) liver cell proliferation persists beyond discontinuation of a CD diet; (ii) the liver contains initiated cells--capable of full evolution to cancer even in the absence of active promotion--after a relatively short 3-month exposure to a CD diet; and (iii) occurrence of a late event(s) is critical for the genesis of the tumors. Whether a CD diet is a complete carcinogen able to initiate de novo liver cells or acts merely as a promoter of the evolution of endogenous initiated cells is briefly discussed. PMID- 3338111 TI - Specific binding proteins for selenium in rat tissues. AB - The preventive and therapeutic potential of selenium (Se), a micronutrient, against cancer has been well documented in several test systems, but the mechanism of its action is not known. The possibility that Se might function in a manner similar to steroid hormones and retinoids through mediation of cellular receptors was examined. A specific 2S cellular binding protein (SeBP) for Na2[75Se]O3 was detected in rat tissue extracts. Liver and intestine exhibited highest levels of SeBP, and heart, uterus and spleen had the lowest levels. Oral administration of Na2[75Se]O3 to rats resulted in its uptake by the tissues with concomitant appearance of [75Se]SeBP complex. The protein binds sodium selenite with moderately high affinity; the apparent dissociation constant was determined by Scatchard analysis to be 1.1 X 10(-7) M. SeBP focused at pH 5.3 upon isoelectric focusing in ampholines of pH 3-10. Competitive binding affinity studies with unlabeled test compounds revealed that selenium dioxide and selenocystine showed high binding affinity (90-95%) for the selenite-binding site on SeBP. Sodium selenate, elemental Se powder, and selenomethionine, however, showed poor competition with sodium selenite. Biological activity of the above selenocompounds, as expressed by others, correlate with their binding affinities for SeBP. Sodium sulfite showed 35% inhibition of Na2[75Se]O3 binding, but sulfate showed none. Two ultimate carcinogens, N-methyl-N-nitrosourea and N methyl-N'-nitro-N-nitrosoguanidine, and two retinoids, retinol and retinoic acid, showed less than 10% inhibition of binding. Interaction of Se with SeBP is completely blocked by thiol inhibitors. Plasma transport of Na2[75Se]O3 is mediated by a protein with a mol. wt of 68,000, which is presently identified, by immunoprecipitation studies as well as by Affi-Gel Blue column chromatographic experiments, as serum albumin. The results suggest that the plasma transport of Se is facilitated by albumin, and that the intracellular transport of Se for its biological functions is accomplished by SeBP. PMID- 3338112 TI - Repair of alkylated purines in the hepatic DNA of mitochondria and nuclei in the rat. AB - Further evidence for the preferential interaction of carcinogens with mitochondrial DNA (mtDNA) has been obtained. In rats treated with high doses of N nitrosodimethylamine (NDMA) or N-nitroso-N-butylurea (NBU), hepatic mtDNA contains 1.4 times more O6-methyl-2'-deoxyguanosine (O6-MedG) or 2.3 times more O6-butyl-2'-deoxyguanosine (O6-BudG) than does nuclear DNA (nDNA). The kinetics of removal of O6-MeG from mtDNA and nDNA are similar at both high (20 mg/kg) and low (2 mg/kg) doses of NDMA, and the removal of O6-MeG can be increased by pretreating the animals with 2-acetylaminofluorene (AAF), indicating that O6-MeG is repaired in the mitochondrion by a mechanism similar to that which functions in the nucleus. In contrast, O6-BudG is removed very slowly from mtDNA and rapidly from nDNA, an observation which is consistent with the absence of a nucleotide excision mechanism in the mitochondrion and the repair of O6-BudG, predominantly by an excision mechanism, in the nucleus of mammalian cells. A 23 kd methyltransferase (MT) protein, similar to the one found in the nucleus, has been isolated from hepatic mitochondria and is present in mitochondria from which the outer membrane has been removed. It is suggested that O6-MeG, but not O6-BuG can be repaired from mtDNA by a MT protein that is nuclear encoded and transported across the mitochondrial membrane. PMID- 3338113 TI - An animal model for neuroendocrine lung cancer. AB - Neuroendocrine lung cancer is among the most common types of lung tumor in man and demonstrates a strong etiological association with cigarette smoking. However, despite numerous efforts, this cancer type has never been induced in animals. This report describes, for the first time, the reproducible induction of pulmonary neuroendocrine cancer in a readily available hamster model. The data provide evidence that deviations from pre-existing normal pulmonary oxygen levels may be an essential factor for the induction of this malignancy. This new model should greatly facilitate studies of the pathophysiology, biochemistry and therapy of neuroendocrine cancer of the lung. PMID- 3338114 TI - DNA adduct formation of aristolochic acid I and II in vitro and in vivo. AB - Aristolochic acid I (AA I) and aristolochic acid II (AA II), the two main ingredients of the carcinogenic plant extract aristolochic acid (AA), are metabolized to reactive intermediates which bind covalently to DNA in vitro and in vivo. DNA adduct formation was analysed by the 32P-postlabelling assay. In in vitro incubations with rat liver 9000 g supernatant (S9) and calf thymus DNA (CT DNA), AA I showed an identical pattern of DNA adducts on thin-layer chromatograms under aerobic and anaerobic conditions, whereas AA II gave rise to DNA adduct formation only anaerobically. The anaerobically obtained DNA adduct pattern by AA II in vitro was similar to the AA I adduct patterns. Aristolactams I and II, the metabolites of AA I and AA II formed under anaerobic conditions, did not form DNA adducts in the presence of S9 mix and CT-DNA. Incubations with xanthine oxidase, known to enzymatically reduce aromatic nitro groups, also activated AA I and AA II to reactive intermediates, producing almost identical adduct patterns as obtained by S9 mix-mediated metabolism. Activation of AA I by S9 mix in the presence of poly(dG) resulted in the formation of two adducts, one of which was shown to be chromatographically indistinguishable from an adduct obtained by reaction with CT-DNA. For the in vivo studies AA I and AA II were administered orally to male Wistar rats, and DNA from liver, brain, oesophagus, stomach lining, forestomach lining, kidney and bladder was analysed for DNA adducts by 32P-postlabelling. The adduct patterns in DNA from forestomach and kidney--target tissues of AA--and DNA from non-target tissues like stomach lining and liver were similar to the patterns obtained from the in vitro incubations. In the bladder (also a target tissue) only AA II gave rise to DNA adduct formation. These findings suggest that DNA adduct formation by AA I and AA II does not directly correlate with the initiation of the carcinogenic process and subsequent tumour formation in target tissues in the rat. PMID- 3338115 TI - Palmitoylcarnitine reverses 12-O-tetradecanoylphorbol-13-acetate-induced refractory state for the TPA-caused ornithine decarboxylase induction in mouse epidermis. AB - When a single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) was performed 12 h before the second application, ornithine decarboxylase (ODC) induction by the second application of TPA was markedly suppressed (refractory state). However, at intervals of 96 h between the first and the second application, the ODC activity induced by the second application of TPA was higher (enhanced state) than the activity induced by the single application. When various anti-tumor promoting agents, i.e. p-bromophenacyl bromide, nordihydroguaiaretic acid, quercetin, 1-tosylamide-2-phenylethyl chloromethyl ketone, retinoic acid and palmitoylcarnitine, were applied concurrently with the first TPA application, the ODC induction in the refractory state was restored only by palmitoylcarnitine, but not by other antitumor promoting agents. None of these anti-tumor promoting agents affected the ODC induction in the enhanced state. Stearoylcarnitine also had the restorative effect but was less effective than palmitoylcarnitine. Acetylcarnitine and palmitic acid were not effective. Pretreatment of mice with TPA 12 h or 96 h before the second TPA application resulted in the reduction or the increase in the Vmax values of ODC both for ornithine and pyridoxal-5'-phosphate, respectively. Palmitoylcarnitine restored these reduced Vmax values to the control values. Twelve hours after TPA treatment, the epidermal protein kinase C activity of both cytosol and particulate fractions decreased moderately. At 96 h after TPA application, protein kinase C activities of both cytosol and particulate fractions were fully or at least partially restored to the control levels. Protein kinase C activities both in the cytosol and the particulate fractions tended to be restored by palmitoylcarnitine, but the effect was not always reproducible. The TPA-induced refractory state and the enhanced state for ODC induction appear to result from the changes in the protein kinase C activities caused by TPA. However, it is not known whether such changes in the protein kinase C activities are the major causes for the TPA-induced refractory and/or enhanced state for ODC induction and whether or not the restorative effect of palmitoylcarnitine is due to its modulating action on protein kinase C activity. PMID- 3338117 TI - Measurement of MeIQx and DiMeIQx in fried beef by capillary column gas chromatography electron capture negative ion chemical ionisation mass spectrometry. AB - A gas chromatographic-mass spectrometric assay has been developed for the simultaneous measurement of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) in fried beef. The method employs capillary column gas chromatography, electron capture negative ion chemical ionisation mass spectrometry and a stable isotope labelled analogue of MeIQx (the synthesis of which is described) as common internal standard. Two patties of lean minced beef which had been cooked separately were analysed and found to contain both compounds (patty 1-2.4 ng MeIQx/g meat, 1.2 ng DiMeIQx/g meat; patty 2-1.3 ng MeIQx/g meat, 0.5 ng DiMeIQx/g meat). Neither compound was present in the meat prior to cooking. PMID- 3338116 TI - Effect of retinol and cigarette-smoke condensate on dye-coupled intercellular communication between hamster tracheal epithelial cells. AB - The dye-coupled intercellular communication across gap junctions in primary hamster tracheal epithelial cells has been studied in serum-free, hormone supplemented medium. In the absence of vitamin A, non-cytotoxic concentrations of cigarette-smoke condensate (CSC) inhibited intercellular communication between tracheal epithelial cells in a concentration-dependent way. All-trans retinol and retinoic acid showed biphasic effects on intercellular communication depending on their concentration. Physiological concentrations of retinol and retinoic acid increased the dye-coupled transfer of Lucifer Yellow CH via gap junctions compared with the dimethylsulfoxide-treated tracheal epithelial cells. At pharmacological concentrations retinol slightly increased the intercellular communication in the first 2 h of the exposure period, whereas upon longer treatment times with retinol and retinoic acid, gap-junction-mediated intercellular communication was inhibited almost completely. When retinol was given to tracheal epithelial cells before exposure to CSC or simultaneously with CSC-exposure, retinol counteracted the inhibitory potential of CSC on intercellular communication. The results of the present study clearly indicate that both CSC and all-trans retinol influence the intercellular communication between primary hamster tracheal epithelial cells in serum-free, hormone supplemented culture medium. PMID- 3338118 TI - Nonuniform epicardial activation and repolarization properties of in vivo canine pulmonary conus. AB - The relation between nonuniform epicardial activation and ventricular repolarization properties was studied in 14 pentobarbital anesthetized dogs and with a computer model. In 11 dogs, isochrone maps of epicardial activation sequence were constructed from electrograms recorded from the pulmonary conus with 64 electrodes on an 8 X 8 grid with 2-mm electrode separation. The heart was paced from multiple sites on the periphery of the array. Uniformity of epicardial activation was estimated from activation times at test sites and their eight neighboring sites. Acceleration shortened and deceleration prolonged refractory periods. The locations of acceleration and deceleration sites of activation differed during drives from various sites, and differences in uniformity of activation during pairs of drives were correlated to differences in refractory periods (r = 0.76, range 0.59-0.93). In three additional experiments, transmural activation sequence maps were constructed from electrograms recorded from needle mounted electrodes placed upstream and downstream to epicardial activation delays. Activation proceeded from epicardium to endocardium upstream to the delays and from endocardium to epicardium downstream to the delays. A computer simulation of two-dimensional action potential propagation based on the Beeler Reuter myocardial membrane model provided insights to the mechanism for the results of the animal experiments. The two-dimensional sheet modeled the transmural anisotropic histology of the canine pulmonary conus and corresponded to previous reports and histology of specimens from five experiments. Simulated activation patterns were similar to those found in the experimental animals. In addition, action potentials were electronically prolonged at sites of deceleration and shortened at sites of acceleration, results comparable to the animal experiments. Our findings demonstrate that the location of areas of nonuniform epicardial activation is dependent on drive site and that nonuniform activation electronically modulates repolarization properties. Therefore it seems likely that the site of origin of ectopic ventricular complexes, especially in ischemic myocardium where activation is nonuniform, could be an important determinant of whether ectopic activity initiates sustained tachyarrhythmias. PMID- 3338119 TI - Facilitating effect of cold shock on recovery from anoxia-induced contractile depression in isolated rat heart and heart muscle. AB - The effect of rapid cooling on the recovery process from anoxia-induced hypodynamic state was studied in isolated rat ventricular muscle and ventricle. Following 10-15 minutes' perfusion of N2-saturated Krebs solution, the muscle was reoxygenated. When the muscle was rapidly cooled for 10-30 seconds during the early phase of reoxygenation, the rate of recovery from contracture significantly increased (p less than 0.01). Rapid cooling was also effective on the recovery from contracture induced by superfusion of Krebs solution with lowered sodium chloride concentration, but it did not affect the recovery from rigor induced by CN-. In the recovery from sustained anoxia (60 minutes), cooling facilitated reattainment of tension development and reduction in contracture tension. Similarly, in whole heart, 2-3 episodes of rapid cooling for about 60 seconds significantly accelerated the recovery of pressure development after 30 minutes of anoxia. At 60 minutes after reoxygenation, pressure development in hearts that were reoxygenated without rapid cooling was 29.8 +/- 26.9% (mean +/- SD) of pressure developed before anoxia. This value increased to 93.8 +/- 27.5% following recurrent rapid cooling (p less than 0.001). At the same time, rapid cooling prevented any significant elevation in resting tension (development of oxygen paradox). These results indicate that excess intracellular calcium ions were removed by rapid cooling. This relief of the myocardium from calcium overload is believed to improve mitochondrial function and result in facilitated recovery of contractile activity. PMID- 3338120 TI - Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle. AB - The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellular calcium concentrations ([Ca2+]o), and at different initial muscle lengths. The endocardial surface was damaged by gentle abrasion of the muscle surface with a plastic blade or by brief immersion for 1 second with 1% Triton X 100. Although there was no evidence of damage to myocardial cells, damaging the endocardial surface resulted in an immediate and irreversible abbreviation of the twitch contractions with, except at the highest ([Ca2+]o, a decrease in peak isometric twitch tension. These changes induced 1) an asymmetrical shift of the tension-[Ca2+]o relation towards increasing [Ca2+]o but with no effect at the highest [Ca2+]o, and 2) a rightward and downward shift of the length-tension relation. Both shifts were significantly more pronounced at 37 degrees C than at 29 degrees C; they were not accompanied by significant changes in Vmax. The asymmetrical shift of the tension-[Ca2+]o relation suggests that the endocardium mediated chain of events may be mediated by changes in the sensitivity of the contractile proteins to Ca2+. This hypothesis is also supported by the similar pattern of changes (i.e., modulation of the onset of early tension decline) induced by decreasing length at each [Ca2+]o and by the removal of a functional endocardium. Accordingly, the endocardium may help to control the performance of the heart by modulating peak contractile performance and relaxation of the underlying myocardium. PMID- 3338122 TI - Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs. AB - We calculated the wavelength of the atrial impulse in chronically instrumented conscious dogs by measuring both conduction velocity and refractory period: wavelength = refractory period X conduction velocity. Implantation of multiple stimulating and recording electrodes allowed wavelength determination at four different areas: the right and left parts of Bachmann's bundle and the free walls of the right and left atria. During programmed electrical stimulation, three types of arrhythmias were observed: rapid repetitive responses, atrial flutter, and atrial fibrillation. During normal rhythm, the wavelength of the atrial impulse varied between 14 and 18 cm. Premature beats had a shorter wavelength, depending on the degree of prematurity. Premature beats that evoked rapid repetitive responses showed a critical shortening of the wavelength below 12.3 cm. Episodes of atrial flutter were induced at a wavelength below 9.7 cm, while fibrillation occurred at wavelengths shorter than 7.8 cm. We correlated the induction of these arrhythmias with the values of refractory period, conduction velocity, and wavelength during control and during administration of several drugs. Intravenous administration of acetylcholine shortened the wavelength by 30 40%, mainly because of refractory period shortening. Both propafenone and lidocaine had strong but opposite effects on refractoriness and conduction and, consequently, little effect on the wavelength. Quinidine markedly prolonged the refractory period, but prolongation of wavelength was less because of a simultaneous decrease in conduction velocity. d-Sotalol also increased refractory period, but because it had no appreciable effect on conduction velocity, this drug was the most effective in prolongation of wavelength. Linear discriminant analysis of the data showed that the refractory period and the conduction velocity each were poor parameters to predict the occurrence of the different arrhythmias (predictive value 48% and 38%, respectively). The combination of both properties, however, as expressed in the wavelength, was a more reliable index that predicted the induction of the different arrhythmias correctly in 75% of the cases. We conclude that the wavelength is a useful parameter for evaluating antiarrhythmic drugs. PMID- 3338121 TI - Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure. AB - The role of lipid abnormalities in the pathogenesis of focal glomerulosclerosis was investigated in the rat remnant kidney model of chronic renal failure. Rats subjected to right nephrectomy and two-thirds segmental infarction of the left kidney (5/6 nephrectomy) were treated for 10 weeks with the lipid-lowering agent clofibric acid. Both serum cholesterol and urine albumin excretion were significantly reduced by clofibric acid. At 10 weeks, the percent of glomeruli with focal glomerulosclerosis was 5 +/- 2% in clofibric acid-treated and 24 +/- 5% in untreated 5/6 nephrectomy rats (p less than 0.01). Inulin clearance was greater in clofibric acid-treated than in untreated 5/6 nephrectomy rats (0.28 +/ 0.02 versus 0.22 +/- 0.02 ml/min 100 g body wt, p less than 0.05). Body weight, kidney weight, and systemic blood pressure were not significantly altered by clofibric acid. Micropuncture studies, performed in separate groups of clofibric acid-treated and untreated 5/6 nephrectomy rats, demonstrated elevated single nephron glomerular filtration rates and glomerular capillary pressures 4 weeks after surgery. However, clofibric acid did not significantly alter single nephron glomerular filtration rates (95 +/- 2.1 nl/min in treated versus 97.0 +/- 6.2 nl/min in untreated, p greater than 0.05) or glomerular capillary pressures (56.6 +/- 1.5 mm Hg in treated versus 57.8 +/- 0.8 mm Hg in untreated, p greater than 0.05) in 5/6 nephrectomy rats. In a separate set of experiments, 5/6 nephrectomy rats were treated with the specific cholesterol synthesis inhibitor, mevinolin. Mevinolin improved serum lipid levels and reduced albuminuria in 5/6 nephrectomy rats without causing significant alterations in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338123 TI - Prevalence of ischemic resting and stress electrocardiographic abnormalities and angina among 40- to 59-year-old men in selected U.S. and U.S.S.R. populations. AB - The prevalence of electrocardiographic (ECG) abnormalities and angina was investigated in 40- to 59-year-old men from two samples, one from a U.S.S.R. study in two locations and one from a U.S. study in nine locations. ECG abnormalities were defined by the Minnesota code and angina was defined by the Rose questionnaire. No differences were found in the prevalence of major Q waves and major or minor ischemia between the two samples, but differences were found in specific indicators of major ischemia. Major ischemic changes were more prevalent in older subjects in both samples. Estimated prevalence of angina was 50% less in the U.S. sample than in the U.S.S.R. sample, and this was consistent with the proportion of subjects excluded from the exercise test because of angina. In both samples, subjects with ECG abnormalities had higher systolic blood pressures. No difference in exercise test abnormalities was found between samples; however, more subjects with a history compatible with coronary artery disease were excluded from the U.S.S.R. sample. PMID- 3338125 TI - Accentuated antagonism between beta-adrenergic and vagal effects on ventricular refractoriness in humans. AB - The purpose of this study was to determine whether there is accentuated antagonism between sympathetic and vagal effects on ventricular refractory periods (VRPs) in humans. The effects of 0.04 mg/kg of atropine on the right ventricular effective and functional refractory periods were determined in the setting of beta-adrenergic blockade by propranolol (0.15 mg/kg loading dose, then 0.1 mg/min continuous infusion, group 1) and in the setting of beta-adrenergic stimulation by 25 or 50 ng/kg/min isoproterenol (groups 2 and 3, respectively). Groups 4 to 6 served as control groups. In group 4, VRPs were determined on three occasions separated by 10 min each in the absence of drug. VRPs also were determined on two occasions after infusion of propranolol (group 5) or 25 ng/kg/min of isoproterenol (group 6). Groups 1 to 4 consisted of 10 subjects each, and groups 5 and 6 consisted of five subjects each. VRPs were determined with the use of basic drive cycle lengths of 600, 500, 400, and 350 msec. Because of sinus tachycardia, sufficient data for comparison of groups 1 to 3 were available only at drive cycle lengths of 400 and 350 msec. Atropine significantly shortened the VRPs in groups 1 to 3, but the magnitude of atropine's effects in group 3 (5.3% to 5.8% shortening at drive cycle length of 350 msec) was significantly greater than in group 1 (2.6% to 3.0% shortening, p less than .05) Data from the control groups demonstrated that there was no effect of time on measurement of VRPs either in the drug-free state or in the presence of propranolol or isoproterenol. The results of this study indicate that cholinergic tone lengthens VRPs in the absence of background sympathetic activity and that this lengthening of VRPs may become accentuated during beta-adrenergic stimulation. PMID- 3338124 TI - Arterial baroreflex control of sympathetic nerve activity during elevation of blood pressure in normal man: dominance of aortic baroreflexes. AB - Arterial baroreceptors in the carotid sinus (CBR) and aortic arch (ABR) regions exert important control over heart rate and peripheral vascular responses to changes in arterial pressure. The relative roles of these two baroreflex pathways on control of sympathetic nerve activity during sustained elevation of arterial pressure in man is unknown. We therefore studied the relative contributions of the carotid versus the aortic baroreflexes on the control of muscle sympathetic nerve activity (MSNA) during elevation of arterial pressure in normal human subjects. In eight normal men (group I), we measured MSNA (microneurography) during sustained elevation of arterial pressure produced by intravenous infusion of phenylephrine (PE) alone (combined ABR and CBR activation) versus during PE infusion with superimposed application of sustained external neck pressure (NP). NP was applied during sustained PE infusion to eliminate the increase in transmural carotid sinus pressure and thus remove CBR activation, thereby causing ABR stimulation alone. Mean arterial pressure was measured directly, central venous pressure was held constant during PE infusion, and MSNA was measured as total activity (burst frequency X amplitude) and expressed as units. Infusion of PE (ABR and CBR activation) increased mean arterial pressure from 87.2 +/- 2.8 to 94.9 +/- 2.9 mm Hg (+/- SE, p less than .001). This was accompanied by a decrease in heart rate from 65.8 +/- 3.4 to 56.1 +/- 3.3 beats/min (p less than .001) and a decrease in MSNA from 236.2 +/- 47.5 to 84.5 +/- 19.3 units (p less than .001). During infusion of PE with superimposed NP (ABR activation alone), mean arterial pressure increased further to 101.2 +/- 2.9 mm Hg (p less than .001 versus control or PE alone), and heart rate returned to control levels of 62.9 +/- 2.0 beats/min (p = NS vs control; p less than .01 PE vs PE plus NP), but MSNA remained reduced at 48.6 +/- 9.2 units (p less than .01 vs control; p = NS vs PE alone). Thus, combined activation of ABR and CBR resulted in a 65 +/- 5% attenution of MSNA, while activation of ABR alone resulted in a 73 +/- 7% attenuation of MSNA. In a separate series of experiments in seven subjects (group II) we used sustained external neck suction alone to activate the CBR (leaving the ABR either unchanged or minimally deactivated) and studied the MSNA responses to this CBR activation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3338126 TI - Circadian occurrence of symptomatic paroxysmal supraventricular tachycardia in untreated patients. AB - Fifty-two patients with paroxysmal supraventricular tachycardia were studied to determine whether there was a circadian pattern to the occurrence of this arrhythmia. Antiarrhythmic therapy was discontinued, and patients were followed until they had one recurrence of tachycardia documented by telephone transmission of the electrocardiogram. By least-squares analysis, the times of day that the 52 attacks (one from each patient) occurred were fit to a sinusoidal density function with a period of 24 hr. The highest relative incidence of tachycardia was at 4 P.M.; tachycardia was five times more likely to occur at 4 P.M. than at 4 A.M., the time of the lowest relative incidence. A second attack of tachycardia was recorded from 35 of the 52 patients. The times of the two attacks in individual patients were found to be independent; thus the times of day at which the second attacks occurred were used as a test set for the distribution estimated from the first. The empirical distribution for the times from the 35 second attacks was compared with the distribution function estimated from the 52 first attacks, and there was no significant departure; this finding confirmed the circadian pattern. Since the relative incidence of attacks of paroxysmal supraventricular tachycardia is higher in the afternoon, it may be helpful to target antiarrhythmic therapy to that time of day. PMID- 3338128 TI - Doppler mapping of postoperative left atrioventricular valve regurgitation. AB - Left atrioventricular valve regurgitation often occurs as a postoperative hemodynamic complication from repair of an atrioventricular septal defect. In this study, cross-sectional two-dimensional Doppler flow mapping of the left atrium was used to quantify postoperative regurgitant flow in 29 patients. Its severity and location was related to the shape of the three leaflets of the left component of the atrioventricular valve, especially to the size of the mural leaflet. To identify which leaflet configuration was likely to cause regurgitation, the position of the leaflets was obtained from the parasternal short-axis view and the angular size of the mural leaflet expressed in degrees of an arc. Doppler mapping was performed in the apical four-chamber and the parasternal long-axis views, dividing the left atrium in nine squares in each. Regurgitation was defined as a jetlike systolic downstroke of the Doppler frequency shift in early systole. The angular size of the mural leaflet varied from 38 to 144 degrees (mean 86 +/- 36 SD). Massive regurgitation (six to nine sites) was encountered in seven patients, five with a mural leaflet size of over 110 degrees, one with mural leaflet size between 70 and 110 degrees, and one with a mural leaflet size of under 70 degrees. No or minimal regurgitation was encountered in 10 patients, three having a mural leaflet size of 70 to 110 degrees and seven with a mural leaflet size of less than 70 degrees. These data suggest that massive regurgitation is encountered in patients with large mural leaflets, whereas patients with smaller mural leaflets tend to have no or mild regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338127 TI - New diagnostic evidence on the T wave map indicating involved coronary artery in patients with angina pectoris. AB - To define the clinical significance of T wave map changes in patients with angina at rest, body surface isopotential T distributions were obtained in 48 patients with single-vessel disease (left anterior descending artery, 34; right coronary artery, eight; left circumflex artery, six) documented angiographically and were compared with those in 120 healthy subjects and those in 19 patients with left ventricular overload whose electrocardiograms showed negative T waves accompanied by an increase in R wave amplitude in left precordial leads. The T wave map abnormalities were observed in 24 of 48 patients (50%) with angina and were classified into three types: (1) type I (18 patients, 37.5%) was characterized by a segmental negative potential in the positive area located at the left thorax and the minimum at the peak of T wave positioned in the upper portion of the left anterior chest, (2) type II (three patients, 6.3%) was characterized by a negative potential with a minimum in the inferior thorax and an indentation of negative potential at the lower margin of the positive potential located over the upper thorax, and (3) type III (three patients, 6.3%) was characterized by a negative potential with a minimum at the back throughout the period of T wave. All patients showing T wave map abnormalities of type I had a significant stenosis of the left anterior descending artery. Likewise, all patients with type II or III had single-vessel disease of the right coronary or left circumflex artery, respectively. All types of T wave map changes observed in patients with angina were different from those in patients with left ventricular overload, whose maps showed the generalized negative potential at the inferior thorax and the left back and the minima clustered at the precordium. In seven patients with lesions of the left anterior descending artery, T wave map abnormalities of type I recovered to normal after successful percutaneous transluminal coronary angioplasty. The behavior of the negative potential and its extrema on the T wave map, which was not available from routine electrocardiography, was indicative of the involved coronary artery and probably of its associated ischemic area in one half of our patients with angina pectoris. PMID- 3338129 TI - Videodensitometric analysis of human coronary stenoses: validation in vivo by intraoperative high-frequency epicardial echocardiography. AB - Videodensitometry is a nongeometric method of coronary angiographic analysis that can be used to provide an index of coronary luminal area. However, there are few direct studies in vivo of the relationship of videodensitometric data to independent measures of luminal area in humans. Although videodensitometry is theoretically independent of angiographic projection and luminal shape, validation of these assumptions in vivo is also limited. We therefore used intraoperative high-frequency epicardial echocardiography, a technique that can directly determine human coronary luminal area and shape in vivo, to further validate videodensitometry. A total of 36 arterial segments in the left anterior descending and right coronary arteries were studied by videodensitometry and high frequency echocardiography. Videodensitometry was performed on angiograms in which the arterial segment of interest was not markedly foreshortened and was uniformly filled with contrast. In 22 discrete lesions (13 with circular lumens and nine with oval or complex lumens), videodensitometric and echocardiographic measures of luminal area correlated well (r = .86). In 33 coronary arterial segments, the effect of angiographic projection on videodensitometry was determined by comparison of the results of videodensitometry performed on left anterior oblique vs right anterior oblique angiograms of the segments. Here too, the correlation was good (r = .94, y = 1.04x + 0.002). The good correlation of left anterior oblique with right anterior oblique videodensitometric results held true for lesions with circular and oval or complex lumens. This study further validates the ability of videodensitometry to provide an index of coronary luminal area and confirms in vivo previous assumptions that the results of videodensitometric analysis are independent of angiographic projection and luminal shape. PMID- 3338130 TI - Treatment of torsade de pointes with magnesium sulfate. AB - Twelve consecutive patients who developed torsade de pointes (polymorphous ventricular tachycardia with marked QT prolongation, TdP) over a 4 year period were treated with intravenous injections of magnesium sulfate. In nine of the patients a single bolus of 2 g completely abolished the TdP within 1 to 5 min, and in three others complete abolition of the TdP was achieved after a second bolus was given 5 to 15 min later. Nine of the patients also received continuous infusion of MgSO4 (3 to 20 mg/min) for 7 to 48 hr until the QT interval was below 0.50 sec. In nine of the 12 patients the TdP was induced by antiarrhythmic agents. The QT interval preceding TdP ranged from 0.54 to 0.72 sec. After the MgSO4 bolus, which prevented the recurrence of TdP, no significant changes were observed in the QT interval. There were no side effects of this treatment. In eight of the 12 patients potassium levels before the TdP were below 3.5 meq/liter; magnesium levels were available in eight patients before TdP, and were normal in all. Five additional patients with polymorphous ventricular tachycardia but normal QT intervals (non-TdP patients) received two to three boluses of MgSO4. This treatment was ineffective in all, but they responded to conventional antiarrhythmic therapy. Thus, MgSO4 is a very effective and safe treatment for TdP, and its application is rapid and simple. Its use is therefore recommended as the first line of therapy for TdP. PMID- 3338131 TI - Mechanisms mediating the heart rate response to hypoxemia. AB - We studied the effect of phasic pulmonary afferent information on heart rate (HR) during a progressive reduction in oxygen saturation (SaO2). The Hering-Breuer reflex was evaluated with the use of the ratio of apnea duration after lung inflation to the preceding expiratory time (dT). Phasic afferent activity was stopped in anesthetized, paralyzed dogs by constant-flow ventilation (CFV), a technique that removes cyclic changes in lung volume. During normocapnic (PaCO2 = 36.4 +/- 1.1 mm Hg) spontaneous breathing, there was a wide variability in HR response, with a mean delta HR/delta SaO2 (+/- SE) of 0.62 +/- 0.27 beats/min/% (values greater than 0 indicate a tachycardiac response). There was a good correlation between delta HR/delta SaO2 and dT (r = .79). Mean delta HR/delta SaO2 for the combined normocapnic and hypercapnic studies during CFV was lower ( 1.32 +/- 0.19 bpm/%) than that during spontaneous breathing (0.23 +/- 0.19, p less than .0001). We suggest that the HR response to hypoxemia is strongly related to the strength of the Hering-Breuer reflex, which may explain the large interdog variability in HR responses. PMID- 3338132 TI - Improved accuracy of echocardiographic endocardial borders by spatiotemporal filtered Fourier reconstruction: description of the method and optimization of filter cutoffs. AB - The usefulness of digitized echocardiographic borders in quantitative regional left ventricular function analysis has been limited by the wide reported range for normal wall motion with this technique. We postulated that random error in endocardial border positioning is a major cause of this limitation. To test this hypothesis, we traced the endocardial borders field by field from 17 complete echocardiographic cycles in six dogs. These cycles showed a great deal of random movement, with each endocardial point reversing its motion an average of 18.5 times per cardiac cycle. Spatiotemporal Fourier analysis of these sequences demonstrated that most of the valid information on endocardial motion was contained in the first four temporal harmonics and the first seven spatial harmonics and that beyond these points the Fourier transform has the spectral characteristics of noise. Reconstruction of these 17 cycles eliminating all Fourier components above the sixth temporal and eighth spatial harmonics reduced the mean number of endocardial reversals per cycle to 2.3 (p less than .00001). To derive the optimal temporal and spatial cutoffs, we compared reconstructions of each of the 17 cycles with three M mode echocardiograms obtained simultaneously with the cross-sectional images. Fourier cutoffs were varied between two and 20 harmonics and demonstrated that the optimal temporal cutoff was 5.5 harmonics and optimal spatial cutoff 6.9. With optimal filtering, the correlation between ventricular diameter derived from the M mode and from the cross-sectional images was r = .965, compared with .877 for the M mode vs unfiltered cross-sectional data (p less than .0001). We conclude that two dimensional filtered Fourier reconstruction significantly improves the accuracy of traced echocardiographic borders. This technique should be useful in the postprocessing of endocardial borders extracted by automated edge detection schemes and should also be applicable to cardiac images derived from modalities other than echocardiography. PMID- 3338134 TI - Inducible sustained ventricular tachycardia 4 years after experimental canine myocardial infarction: electrophysiologic and anatomic comparisons with early healed infarcts. AB - We studied a group of 17 dogs 4 to 6 years after infarction produced by 2 hr occlusion of the anterior descending coronary artery followed by reperfusion. Dogs in this "late" infarct group were compared with a group of 24 dogs with "early" healed infarcts (2 to 24 weeks old). With signal-averaging techniques body surface potentials were recorded during sinus rhythm. After thoracotomy epicardial electrograms were recorded from 45 standardized sites within the infarcted region and characteristics of selected electrograms were compared with anatomic features of underlying myocardium. Epicardial recordings from the late infarct group demonstrated earlier local activation (p less than .001) and shorter electrogram duration (p less than .001) when compared with recordings from the early infarct group. There was less temporal dispersion of activation and electrogram duration among the 45 sites in dogs with late infarcts as measured by respective coefficients of variance (p = .007 and less than .001). With programmed stimulation six dogs in the late and eight in the early infarct group exhibited inducible sustained ventricular tachycardia. Mean cycle length of the tachycardia in dogs with late infarcts was significantly shorter (p = .035). Late potentials were notably less prominent in dogs in the late infarct group with ventricular tachycardia than in dogs in the early infarct group. Fewer abnormal electrophysiologic characteristics of late infarcts coincided with relatively less scar in the underlying myocardium. Moreover, the strength of electrophysiologic-anatomic correlations differed in late as opposed to early infarcts. The latter findings suggest long-term evolution of infarct anatomy. We conclude that a substrate for reentrant tachycardia is present in dogs 4 to 6 years after reperfused infarction. Conduction characteristics are less abnormal in these late healed infarcts and are associated with a shorter ventricular tachycardia cycle length and less pronounced late potentials on the body surface. PMID- 3338133 TI - Reentrant ventricular rhythms in the late myocardial infarction period: prevention of reentry by dual stimulation during basic rhythm. AB - Stimulation at two ventricular sites during basic rhythm as a means of preventing the induction of ventricular arrhythmias in the postinfarction heart was investigated. Isochronal maps of ventricular epicardial activation from dogs were analyzed 4 days after ligation of the left anterior descending coronary artery. Activation patterns were obtained by use of a computerized data acquisition system recording from 62 sites. Effective refractoriness and conduction time during basic paced rhythm (S1) for each site were summed to construct isochronal maps of recovery time. The patterns of recovery time on the heart were eccentrically layered, with a narrow zone of differentially prolonged recovery time along one border of the infarct. The formation of an arc of functional conduction block after premature stimulation (S2) was correlated with regions of differentially prolonged recovery time (59 +/- 30 msec, mean +/- SD) between recording sites spaced 5 to 10 mm apart. The recovery time difference between sites that did not block (17 +/- 14 msec) was significantly shorter. The spatial distribution of recovery time on the heart could be modified by application of stimuli at two sites during the basic rhythm. Reentry was prevented by appropriate placement of the secondary site in the ischemic zone and the temporal sequencing of the paired stimuli. Stimulation at the secondary site "peeled back" refractoriness in the ischemic zone. Prevention of reentry was a result of either: (1) a shift in the arc of conduction block toward the ischemic zone, (2) a reduction in the extent of the continuous arc, (3) early activation of regions distal to the arc, or (4) a combination of the above. In two dogs, the arc of block was abolished entirely after dual stimulation. This report illustrates the criteria for effective prevention of reentry, applied to a well-described verifiable model of reentrant activation. PMID- 3338135 TI - Hyperkinesis without the Frank-Starling mechanism in a nonischemic region of acutely ischemic excised canine heart. AB - To determine the essential mechanism of increased systolic wall motion, i.e., hyperkinesis, in a nonischemic region (NIR) during acute ischemia, we simultaneously evaluated global and regional function of the excised, cross circulated canine left ventricle connected to a volume servo pump before and after coronary occlusion. Regional areas were determined with pairs of orthogonal subendocardial sonomicrometers in the ischemic region (IR) and NIR. After coronary occlusion with left ventricular end-diastolic and stroke volumes kept constant, the amount of systolic area shrinkage (delta A) in NIR increased by 33 +/- 41% (p less than .05), despite a decrease in end-diastolic regional area by 3 +/- 4% (p less than .05). Regional work obtained from the wall tension-regional area (T-A) loop in NIR decreased by 50 +/- 24% due to a similar decrease in afterload despite the presence of hyperkinesis, indicating regional systolic unloading. When left ventricular end-diastolic volume was subsequently increased with a constant stroke volume, delta A in NIR increased at the expense of a further decrease in delta A in IR. The end-systolic T-A relationship in NIR remained unchanged, whereas that in IR markedly shifted rightward, suggesting that the contractile state of NIR was constant. These results indicate that hyperkinesis in NIR during acute ischemia can occur without a utilization of the Frank-Starling mechanism or an enhancement of regional contractile state, and that the essential mechanism of this phenomenon is regional afterload reduction due to an intraventricular mechanical interaction between IR and NIR. PMID- 3338136 TI - Influence of heart rate, preload, afterload, and inotropic state on myocardial ultrasonic backscatter. AB - Ultrasonic backscatter is substantially modified by pathologic changes in myocardium. Influence of physiologic changes in heart rate, mean arterial pressure, preload, and inotropic state were studied in 17 anesthetized open-chest dogs. Heart rate was changed with atrial pacing/ULFS'49 (a selective bradycardiac agent). Mean arterial pressure was varied with aortic constriction/nitroprusside, preload was altered with nitroglycerin/volume infusion, and inotropic states were altered with dobutamine (10 microns/kg)/esmolol (100 microns/kg). IBR5, an optimum weighted frequency average (4 to 6.8 MHz) of the squared envelope of diffraction corrected for absolute backscatter, and the Fourier coefficient of amplitude modulation (FAM), an index of cardiac cycle-dependent variation, were measured from six sequential electrocardiographically gated intervals throughout the cardiac cycle. Heart rate, mean arterial pressure, preload, and inotropic state did not significantly affect IBR5. FAM increased from 3.5 +/- 0.3 dB (mean +/- SEM) to 7.0 +/- 0.4 dB (p less than .01) at a heart rate of 120 beats/min, and decreased to 3.9 +/- 0.4 at a heart rate of 160 beats/min. No change in FAM was noted with a rise (70 +/- 12 to 45 +/- 10 mmHg) in mean arterial pressure or preload (an increase or decrease in diastolic segment length of +/- 10% from the baseline). Dobutamine produced a significant increase in left ventricular dP/dt (2600 +/- 200 to 3475 +/- 275 mm Hg) and FAM (3.4 +/- 0.1 to 6.4; p less than .01). Esmolol significantly reduced left ventricular dP/dt (2600 +/- 200 to 2000 +/- 175 mm Hg, p less than .05) and FAM (3.4 +/- 0.01 to 6.4 +/- 0.1; p less than .01). We conclude that IBR5 is independent of heart rate, mean arterial pressure, preload, and inotropic state. Cardiac cycle-dependent amplitude modulation follows changes in cardiac contraction. PMID- 3338137 TI - Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methylpropyl isonitrile. AB - To study the potential usefulness of technetium-99m hexakis-2-methoxy-2 methylpropyl-isonitrile (Tc-MIBI) as a cardiac perfusion imaging agent, the left circumflex coronary arteries of 12 dogs were partially occluded. Eight additional control dogs had no coronary artery stenosis. Myocardial Tc-MIBI activities in the left circumflex and left anterior descending zones were continuously monitored by miniature implantable radiation detectors for 4 hr after administration of the isotope. The dogs were then killed. Serial gamma camera images were also acquired during the study. Heart rate, arterial blood pressure, pressure distal to the stenosis, and cardiac output did not change significantly during the experiment. Microsphere-determined regional myocardial blood flow was significantly reduced in the left circumflex distribution in the 12 dogs with coronary artery stenoses. In the 12 dogs with left circumflex coronary artery stenoses, the 4 hr fractional Tc-MIBI clearances from the normal and ischemic zones were minimal and equivalent (0.15 +/- 0.05 vs 0.15 +/- 0.07). In the eight control dogs, 4 hr fractional Tc-MIBI clearances from the left anterior descending and left circumflex artery zones were minimal and equivalent (0.11 +/- 0.06 vs 0.10 +/- 0.07). Four hour fractional Tc-MIBI clearance from the blood was 0.98 +/- 0.03 for the dogs with stenosis and 0.97 +/- 0.02 for the dogs without stenosis. One additional dog had complete occlusion of the left circumflex coronary artery followed by administration of Tc-MIBI and scandium-46-labeled microspheres. This heart was immediately sectioned and counted to determine the relationship of regional blood flow to Tc-MIBI distribution (r = .92).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338138 TI - Recommendations for human blood pressure determination by sphygmomanometers. PMID- 3338139 TI - A high-speed liquid-chromatographic method for measuring urinary porphyrins. AB - We describe a rapid quantitative and qualitative "high-performance" liquid chromatographic (HPLC) method for measuring porphyrins in urine. Direct injection of acidified, filtered urine onto a 3-micron (particle size) 3-cm-long reversed phase column fully resolves uroporphyrin, hepta-, hexa-, and pentacarboxylic acid porphyrins, and coproporphyrin. Instrument response is linearly related to concentration over the range 25 to 300 nmol/L. The method provides data essential for the differential diagnosis of porphyric states, including porphyria variegata and porphyria cutanea tarda. This relatively inexpensive method requires a run time of only 8 min per sample, making it particularly suitable for routine use in the clinical chemistry laboratory. PMID- 3338140 TI - Ten commercial kits compared for assay of thyrotropin in the normal and thyrotoxic range. AB - I developed a standard procedure for assessing sensitivity, intra-assay precision, parallelism of sample dilutions, and assay drift, using a single trial assay kit. I used this to compare the performance of 10 commercial kits with an in-house radioimmunoassay for human thyrotropin. No one kit stood out as clearly superior overall. Differences in calibration between kits were evident in a comparison of thyrotropin concentrations measured in clinical samples, and by direct comparison of standards from different kits in a single assay. However, all kits gave clinically consistent results with respect to their published normal reference interval. Moreover, the performance of human thyrotropin assay kits has improved during the 14 months of this study. PMID- 3338141 TI - Improved determination of selenium in serum by Zeeman atomic absorption spectrometry. AB - We have improved Zeeman atomic absorption spectrometric determination of selenium in serum by using an acidic solution of Ag + Cu + Mg as a matrix modifier and performing the charring step in flowing O2. Under these conditions, we could calibrate serum results with selenium standards in bovine albumin solutions. Mean analytical recovery was 98%, and the CV was 1.8% within runs, 2.9% between runs. Analysis of Reference Materials from the U.S. National Bureau of Standards (SRM 909 and RM 8419) yielded the values of 106 (SD 2.4) and 15 (SD 1.6) microgram/L, respectively, in good agreement with the expected values (106 and 16, respectively). The method--being reliable and relatively simple and rapid--is suitable for use in epidemiological screenings. Mean selenium concentrations in serum sampled from 274 adults in central Italy were 90 (SD 15) microgram/L. For 11-year-old children, these values were lower and showed a tendency to sex related difference: 82 (SD 9.9) microgram/L for 97 boys, 78 (SD 9.3) microgram/L for 90 girls. PMID- 3338142 TI - Bias between enzymatic methods and the reference method for cholesterol. AB - Assaying 312 serum samples, we compared four enzymatic methods for serum cholesterol with the Reference Method (modified Abell-Kendall) of the Centers for Disease Control (CDC). The means for the aca, TDx, and SMAC methods (2.27, 2.27, and 2.24 g/L, respectively) were significantly higher (P less than 0.05) than those of the Reference Method and the RA-1000 method (2.19 and 2.18 g/L, respectively). The biased methods had positive proportional and (or) systematic biases. Results with these methods were 2.6% to 4.9% higher than with the Reference Method. The assigned concentrations of cholesterol in the calibration materials for the SMAC and aca agreed with those obtained by the Reference Method, but were lower for the TDx and higher for the RA-1000. These findings document positive biases for cholesterol with three enzymatic methods and suggest that misassignment of calibrators is not primarily responsible for the biases found with the aca and SMAC. It may, however, to be a significant factor for the TDx. PMID- 3338143 TI - Multiple overnight urine collections may be used for estimating the excretion of electrolytes and creatinine. AB - We studied the excretion of sodium, potassium, calcium, magnesium, and creatinine in overnight and 24-h urines collected over a period of seven consecutive days from 28 Dutch boys, ages eight and nine years. The correlation coefficients for the relation between true mean overnight and true mean 24-h excretion ranged between 0.94 and 1.00 for sodium, calcium, magnesium, and creatinine and was equal to 0.61 for potassium. Generally the within-person coefficients of variation for overnight excretions (range, 33-52%) were greater than for 24-h excretions (range 16-35%). We conclude that overnight collections may replace 24 h collections in the case of young boys, but that generally more overnight than 24-h urine specimens are required to achieve a similar degree of precision. The exact number of urine specimens required varies with the aims of the study. PMID- 3338144 TI - Variations in the composition of low- and high-density lipoproteins during the acute phase of myocardial infarction. AB - We analyzed correlations between apolipoprotein B (apo B), cholesterol and phospholipids (preponderant lipids) in low-density lipoproteins (LDL) as well as between apolipoprotein A1 (apo A1) and these same lipids in high-density lipoproteins (HDL), during the acute phase of myocardial infarction. In LDL, a very elevated and stable correlation (r) was observed between these parameters, and the coefficients of regression (b) did not differ significantly during the period studied. In HDL, there was a decrease in r and b values from day 1 to day 2, then an increase after day 2. We hypothesize that these disturbances in HDL composition may be due to a greater endocytosis of LDL at day 2, leading to intracellular increase in cholesterol and phospholipids. Part of these lipids could be taken up by HDL molecules, causing a transient overload. PMID- 3338145 TI - Four assay methods for glycated hemoglobin compared as screening tests for diabetes mellitus: the Islington Diabetes Survey. AB - We assessed the utility of four methods of glycated hemoglobin assay (agar gel electrophoresis with Schiff base, agar gel electrophoresis with prior removal of Schiff base, boronate affinity chromatography, and isoelectric focusing) as screening tests for diabetes mellitus, studying 223 subjects undergoing an oral glucose-tolerance test after fasting and 2 h after ingestion of 75 g of glucose. Assessment of glucose tolerance status according to the 1980 World Health Organization diagnostic criteria indicated that 13 subjects (5.8%) had diabetes, 48 (21.5%) had impaired glucose tolerance, and nine (4.0%) could not be classified (six of these because of missing values). Use of receiver-operating characteristic curves to compare the assays as screening tests showed the affinity chromatography assay to be superior. Assays for glycated hemoglobin after fasting had better precision than post-glucose-load assays as screening tests, and test characteristics of glycated hemoglobin assays on fasting subjects were similar to those of the blood-glucose estimation after fasting. We conclude that measurement of glycated hemoglobin may be a useful screening test for diabetes, and that such measurement of stable glycated hemoglobin is as accurate as measurement of fasting blood-glucose in screening for diabetes. For this use, we found methods that measure stable glycated hemoglobin superior to that measuring both stable and labile Schiff-base fractions. PMID- 3338146 TI - Effects of non-ionic and anionic detergents on lipid-associated tissue ferritin. AB - Lipid-associated ferritin from homogenates of guinea pig liver is released from its conjugate(s) by incubation with the non-ionic detergents Triton X-100 and Nonidet P-40 but not by incubation with the anionic detergent deoxycholate. The amount of lipid-associated ferritin released from its conjugate(s) depends on the concentration of the non-ionic detergents. At a final non-ionic detergent concentration of about 20 g/L, all lipid-associated ferritin is released from its conjugate(s) in a liver homogenate. The amount released is identical with the amount of the lipid-associated ferritin obtained by extraction of the same liver homogenate with a mixture of butanol and diisopropyl ether. PMID- 3338147 TI - Chemical assay of p-aminohippuric acid simplified by use of dimethylaminocinnamaldehyde in ethanol. AB - We have developed a new and simple method of p-aminohippuric acid determination by use of dimethylaminocinnamaldehyde (DACA). It differs from previous methods using DACA in that the reaction is carried out in ethanol rather than in dilute acid. This results in deeper and more stable color development. We have used this method successfully to determine effective renal plasma flow in a clinical study of this variable in pregnant women. PMID- 3338148 TI - Screening method for detection of Bence Jones proteinuria. PMID- 3338149 TI - Fructosamine and Hb A1c in patients with hemoglobinopathies. PMID- 3338150 TI - Immunoturbidimetric C-reactive protein kit adapted to the Technicon RA-1000. PMID- 3338152 TI - Stimulating effects of calcium and magnesium on serum pseudocholinesterase activity. PMID- 3338151 TI - Errors in blood glucose determinations in hemolysates by the glucose dehydrogenase method on the Cobas Mira analyzer. PMID- 3338153 TI - Heparin interferes with aspartate aminotransferase activity determination in the Ektachem 700. PMID- 3338154 TI - High concentrations of tumor-associated trypsin inhibitor in hemodialyzed patients. PMID- 3338155 TI - Immunoturbidimetric assay of transthyretin by random-access analysis. PMID- 3338156 TI - Enzymic determination of total bilirubin in serum with the BA-1000. PMID- 3338157 TI - False-negative latex-agglutination test for myoglobin owing to antigen excess. PMID- 3338158 TI - Immunoturbidimetric micro-albumin kit adapted to the Technicon RA-1000. PMID- 3338159 TI - Effect of extreme humidity and temperature on Seralyzer and Reflotron test strips. PMID- 3338160 TI - Effect of shortened pre-incubation on results for fructosamine in normal, diabetic, and quality-control sera. PMID- 3338161 TI - Effect of not allowing Reflotron strips to warm to room temperature. PMID- 3338162 TI - Evaluation of the Abbott Spectrum "High-Performance" Diagnostic System. PMID- 3338163 TI - Serum chemistry assays in reproduction toxicity testing. PMID- 3338164 TI - Albumin Cooperstown: a serum albumin variant with the same (313 Lys----Asn) mutation found in albumins in Italy and New Zealand. AB - Albumin Cooperstown is an electrophoretically fast genetic variant (alloalbumin) inherited in a family in New York State. To determine the structural change, we separated the alloalbumin from normal albumin A by "high-performance" liquid chromatography, reduced and carboxymethylated it, and cleaved it with CNBr. Isoelectric focusing showed that the substitution was in fragment CB4 (residues 299 to 329). The variant CNBr fragment from the albumin of two siblings was purified by liquid chromatography. Automated sequence analysis established the substitution of lysine-313 by asparagine (313 Lys----Asn), which corresponds to mutation of a single nucleotide base. The same substitution has recently been reported in albumin variants in Italy and New Zealand. This provides the first evidence for independent mutations at a single site within the structure of the mature albumin molecule. Because of the significance of albumin for study of protein evolution, clinical chemists are asked to be on the alert for cases of bisalbuminemia. PMID- 3338165 TI - Galactosemia detection from phenylketonuria screening. AB - We describe a case of classical galactosemia in which the diagnosis was first suggested by the finding of a moderately increased blood-spot phenylalanine concentration. The child was clinically unaffected at six days when the initial sample was collected. Prompt institution of dietary management averted a serious metabolic crisis. PMID- 3338166 TI - Clinical chemistry--quo vadis? PMID- 3338167 TI - Accuracy and blood cholesterol measurements. PMID- 3338168 TI - Current status of blood cholesterol measurement in clinical laboratories in the United States: a report from the Laboratory Standardization Panel of the National Cholesterol Education Program. PMID- 3338169 TI - Plasma malondialdehyde: a poor measure of in vivo lipid peroxidation. PMID- 3338170 TI - Erroneous test results after use of pieced-together rotors in a Cobas Fara centrifugal analyzer confirmed. PMID- 3338171 TI - "Microalbuminuria" or "pauci-albuminuria"? PMID- 3338172 TI - Determination of hemoglobin A1c by liquid chromatography. PMID- 3338173 TI - Erroneous electrolyte results caused by catheters. PMID- 3338174 TI - Citric acid and calcium nephrolithiasis. PMID- 3338175 TI - Quality-control materials for use with monitors of blood glucose. PMID- 3338176 TI - Increased cytosol aminopeptidase in serum in measles infection. PMID- 3338177 TI - Revised method of proton NMR urinalysis for detecting inborn errors of metabolism: a critique. PMID- 3338178 TI - Urinary excretion of digoxin-like immunoreactivity after physical exercise. PMID- 3338179 TI - Variation among instruments in interference by cephalosporin in the Jaffe reaction for creatinine. PMID- 3338180 TI - Gas-chromatographic measurement of carboxyhemoglobin in blood from mothers and newborns. AB - HbCO in blood sampled from 20 mothers and newborns immediately after birth was measured with a new, simple gas-chromatographic method for CO. The mean ratio of HbCO to total hemoglobin for 13 non-smoking mothers did not differ significantly from that for their infants (mean 0.38%, SD 0.26% vs 0.38%, SD 0.13%), but the HbCO ratio varied more in the mothers than in the infants (P less than 0.05). The infants of seven cigarette-smoking mothers, tobacco-abstinent for 7 h during labor, had higher HbCO ratios than their mothers (mean 1.88% vs 1.28%, P less than 0.05). The results are in harmony with the concept of equal affinities of fetal and adult hemoglobin for CO and a long time for passage of CO across the placenta. PMID- 3338181 TI - Heterophilic antibodies: a problem for all immunoassays. AB - We verified that antibody-binding substances in serum that interfere in two-site immunoassays involving murine antibodies are heterophilic antibodies. Incubation of serum containing heterophilic antibodies and a murine monoclonal antibody to human choriogonadotropin (hCG) leads to formation of a series of soluble immune complexes. We investigated the recognition of hCG by reagent antibody in the presence of heterophilic antibodies and found this recognition to be diminished. Consequently, about 30% of serum samples containing heterophilic antibodies falsely appear to contain increased concentrations of hCG. The effect on analyte recognition probably results from steric inhibition of hCG binding to complexed antibody. Heterophilic antibodies detected with a murine antibody also bound immunoglobulin from several other species but did not bind all of those tested. PMID- 3338182 TI - Changes in carnitine in polymorphonuclear leukocytes, mononuclear cells, and plasma from patients with inflammatory disorders. AB - After finding relatively large amounts of carnitine in polymorphonuclear leukocytes and mononuclear cells from healthy subjects, we studied carnitine status in these cells and plasma from 20 patients with inflammatory disorders subsequent to multiple trauma and (or) head injury. The nonesterified carnitine content in polymorphonuclear leukocytes from patients significantly exceeded that in healthy subjects, while it was significantly decreased in mononuclear cells. In addition, the acylcarnitine content of both types of cells from patients was significantly increased. The total carnitine of polymorphonuclear leukocytes from patients was significantly increased, while that in mononuclear cells was unchanged, as compared with healthy subjects. In plasma from patients, nonesterified carnitine was extremely decreased, while both short-chain acylcarnitine and long-chain acylcarnitine were significantly increased. More than half of the carnitine was acylated in polymorphonuclear leukocytes and mononuclear cells in all patients tested, less than half in these cells from healthy subjects. Also, the presence of infection in these patients does increase, but not significantly, the nonesterified and acylcarnitine of both polymorphonuclear leukocytes and mononuclear cells from these patients. PMID- 3338183 TI - Effects of storage and handling conditions on concentrations of individual carotenoids, retinol, and tocopherol in plasma. AB - We investigated the effects of storage and handling on measured values for carotenoids, retinol, and tocopherol in plasma. We found no significant differences in the concentrations of these analytes measured in plasma samples that were frozen immediately after separation as compared with replicate samples maintained at room temperature in the dark for 24 h. Analytes were stable in solvents for at least 18 h at 23 degrees C after extraction. Purging samples with nitrogen gas before freezing had no detectable beneficial effects. All analytes were stable in plasma stored at -70 degrees C for at least 28 months or at -20 degrees C for five months. By 15 months the concentrations of carotenoids were significantly less (P less than 0.05) in plasma stored at -20 degrees C than in plasma stored at -70 degrees C, while retinol and tocopherol concentrations were not significantly different. Concomitant with the decrease in carotenoids was the appearance of unidentified peaks in the ultraviolet. Adding ascorbic acid or butylated hydroxytoluene antioxidants to the precipitating solvent did not alter the losses of carotenoids or alter the appearance of unidentified peaks. Under appropriate conditions, plasma carotenoids, retinol, and tocopherol are stable for more than two years. PMID- 3338184 TI - Purification of anti-apolipoprotein CIII antibodies by exploiting their affinity for apolipoprotein CIII linked to polyacrylamide gel after isoelectric focusing. AB - A new immunoaffinity technique for purifying anti-apolipoprotein CIII antibodies has been developed by isolating bands of apo CIII2 from isoelectric focusing (IEF) gel. Total apo C was obtained from delipidated very-low-density lipoprotein by chromatography on Sephacryl S 200. Apo CIII2 was separated from the apo CII band by IEF on polyacrylamide gel with use of pH 4-6 ampholytes. After sonication of the band in distilled water and various different washes, we directly mixed with antiserum a suspension of apo CIII2 bound to IEF-polyacrylamide gel. After their elution, we tested the specificity of the antibodies by an enzyme immunoassay technique, using plates coated with apolipoprotein, 100 ng per well. No cross-contamination of eluted anti-apo CIII antibodies by anti-apo CII or anti apo E antibodies was observed. This affinity technique is easy to use, rapid to perform, and no sophisticated apparatus is needed. The gels can be used repeatedly and yield reproducible results with a very good analytical recovery (94%). We anticipate that this technique will prove useful for purification of other antibodies, particularly antibodies to apolipoproteins such as anti-apo CII and anti-apo E. PMID- 3338185 TI - Value of a spectroscopic "fecalogram" in determining the etiology of steatorrhea. AB - We have developed a "fecalogram" to present the analytical results for four characteristics of fecal specimens: dry weight, total nitrogen, total fat, and hydrolyzed fat, measured by near-infrared spectroscopy. This technique gives results as precise as those of more traditional analyses for these four components. The respective correlation coefficients are 0.973, 0.960, 0.974, and 0.978. The CVs for this technique range from 1.19% to 2.88%. Among the digestive disorders revealed by this fecalogram is steatorrhea, which can be differentiated as being of pancreatic or intestinal etiology. The percentage of total fat that is hydrolyzed is significantly (P less than 0.0001) greater in patients with malabsorption (greater than 70%) than in those with maldigestion (less than 70%). PMID- 3338186 TI - Effect of lot-to-lot variability in filter paper on the quantification of thyroxin, thyrotropin, and phenylalanine in dried-blood specimens. AB - We prepared whole-blood pools to contain various concentrations of phenylalanine (Phe), thyroxin (T4), and thyrotropin (TSH) and applied them to six different lots of Schleicher & Schuell Grade 903 filter paper, two of which represented extremes for serum-absorbancy. Individual measured T4 values showed minimal overlap among all pools for each individual filter-paper lot and for all lots combined, but Phe values overlapped considerably among the high-concentration pools within and among lots. Individual TSH values also showed considerable overlap among the high-concentration pools for all lots combined, but little overlap within each lot. Maximum differences in mean observed values among lots ranged from 6% to 36% for all analytes. Assay results from hemolyzed blood specimens generally were lower than from intact-cell blood specimens for T4 and TSH, but slightly higher for Phe. Maximum among-lot differences in mean values ranged from 13% to 29% for all analytes when each tested lot was used for assay calibration. Lot-to-lot differences in measured values were not strongly related to serum absorbancy values. We conclude that routinely encountered within- and among-lot filter paper variability, as measured by serum-absorbancy, is not alone sufficient to cause gross quantification errors in neonatal screening programs. PMID- 3338187 TI - An enzymatic method for 5-fluorocytosine. AB - We developed an enzymatic method for determination of 5-fluorocytosine in serum, using creatine iminohydrolase (EC 3.5.4.21), the Cobas-Bio analyzer, and an extant ammonia method. Analytical recovery (y) of drug added to serum (x) was good, with y = 0.97x-0.7, Sy.x = 3.6, r = 0.997 (n = 65) over the range 6.25 to 150 mg/L. Comparison with an HPLC method (x) showed good agreement: y = 0.98x + 1.34, Sy.x = 3.7 (n = 37), as analyzed with the Deming debiased regression. Precision was good, CVs being less than 3% for within-run and less than 6% for between-run controls. Ammonia, amphotericin B, glucose, urea, and hemolysis do not interfere, but bilirubin shows analyte-dependent interference and lipemia interferes when triglycerides exceed 5 g/L. This assay is accurate, inexpensive, and easy to perform. It can be easily adapted for routine or emergency use. PMID- 3338188 TI - Time-resolved immunofluorometric assay of sex-hormone binding globulin. AB - A time-resolved immunofluorometric assay (trlFMA) for human sex-hormone binding globulin (SHBG) is described in which antibody-coated tubes or microliter strip wells and a europium (Eu) chelate-labeled monoclonal antibody are used. The trlFMA sensitivity is similar to that of other SHBG immunoassays, and other analytical variables compare favorably with an SHBG immunoradiometric assay (IRMA) kit and a steroid binding capacity assay: the interassay coefficient of variation (CV) is less than 8% and the intra-assay CV is less than 6% for concentrations between 6 and 200 nmol/L. The reference intervals (means +/- SD) for SHBG concentrations (nmol/L) in serum from 10 men, 10 women, and 10 pregnant women were 23 +/- 12, 65 +/- 39, and 439 +/- 122, respectively. In 14 hirsute women the mean +/- SD serum SHBG concentration (37 +/- 21 nmol/L) was significantly lower (P less than 0.01) than the mean for an age-matched, nonhirsute female comparison group. The trlFMA is technically simple, requires no centrifugation or separation reagent, and takes a counting time of only 1 s. In addition, the Eu-label is nontoxic, presents no waste-disposal problems, and has a long shelf life. PMID- 3338189 TI - Direct spectrophotometry of bilirubin in serum of the newborn, with use of caffeine reagent. AB - We recently described a direct spectrophotometric method for unconjugated bilirubin, with caffeine reagent (Clin Chem 1986;32:1389-93). Because this method is independent of the protein matrix we used it for the preparation of bilirubin standards (Clin Chem 1987;33:1817-21). Now, in this paper, we utilize the caffeine reagent in setting up a bilirubin method for serum from neonates. This resulted in a two-wavelength (465 and 528 nm) equation, which fully corrects for HbO2 interferences. In combination with a bilirubin standard, this equation may be transformed into a simple relative formula for use with this simple dilution method. We studied this two-wavelength method with 55 neonates' sera, comparing results with those by both the diazo method of Doumas et al. (Clin Chem 1985;31:1779-89) and the borate method of Hertz et al. (Scand J Clin Lab Invest 1974;33:215-30). We found that this new method is independent of hemolysis and of the matrix of the sera. Therefore, it is very suitable for use in neonatology. PMID- 3338190 TI - Liquid-chromatographic profiling of solutes in serum of uremic patients undergoing hemodialysis and chronic ambulatory peritoneal dialysis (CAPD); high concentrations of pseudouridine in CAPD patients. AB - Using "high performance" liquid chromatography, we studied non-protein-bound fractions and total concentrations of 18 solutes accumulating in sera from a group of 12 patients who were undergoing chronic ambulatory peritoneal dialysis (CAPD) and in predialysis sera from a group of 15 hemodialysis (HD) patients. We monitored longitudinal changes in solute concentrations for two patients with respect to change of therapy between HD and CAPD. The concentrations of pseudouridine (P less than 0.001), uric acid (P less than 0.001), and an unknown fluorescent solute, "UKF3" (P less than 0.01), differed in sera of HD and CAPD patients. When standardized with respect to serum creatinine concentrations, the concentration of the transfer-RNA catabolite, pseudouridine, was significantly (P less than 0.0001) higher in sera of CAPD patients than in HD patients, suggesting an increase in turnover of transfer RNA. In stepwise linear discriminant analysis, the combination of pseudouridine and the probably biochemically related fluorescent unknown, UKF3, contributed most to the differentiation between sera from CAPD and HD patients. PMID- 3338191 TI - Effects of serum versus plasma on agglutination of antibody-coated indicator cells by human rheumatoid factors. AB - Plasma and serum contain an inhibitor (I) of the agglutination of rabbit IgG coated sheep erythrocytes by human rheumatoid factor (RF). Plasma but not serum contains an inhibitor of the inhibitor (I/I) which allows RF to interact with its target. In normal blood, there is more I than I/I, and I can be removed by solid phase chromatography through concanavalin A (Con A). Plasma I/I is heat labile being eliminated by heating at 56 degrees C for 30 min. Addition of exogenous calcium clots EDTA plasma, causing an irreversible loss of I/I, and suggesting its involvement in the clotting cascade. The absence of I/I from Factor V deficient plasma and destruction of I/I by Russell's viper venom indicate I/I either is associated with or is a part of Factor V. These findings suggest a balanced interplay between I and I/I, and indicate results of immunological tests done in vitro may not accurately reflect immune function in vivo. This seems to represent an unexplored link between hemostasis and immunity. PMID- 3338192 TI - Monocyte-mediated suppression of rheumatoid factor production in normal subjects. AB - The regulatory role of normal monocytes in the production of rheumatoid factor (RF) was investigated. Monocyte depletion from normal mononuclear cells (MNC) resulted in an elaboration of IgM RF in 18 of 20 subjects. The increased RF production was inhibited by the addition to the cultures of adherent cells or their culture supernatants. These observations demonstrate the suppressive role of normal monocytes in the production of RF. Supernatants obtained from normal monocytes cultured with indomethacin could suppress the RF production, suggesting that prostaglandin E2 may not be involved in the regulation of IgM RF production. PMID- 3338193 TI - Quantitation and IgG subclass distribution of antichromatin autoantibodies in SLE mice. AB - Antibodies to a native chromatin preparation were found in most mice suffering from spontaneous SLE. All MRL/Mp-lpr/lpr (MRL/lpr) sera tested (more than 500) contained antibodies to chromatin and antichromatin levels increased with age. Approximately 50% of the IgG antichromatin antibody in the MRL/lpr sera was of the IgG2a subclass, 30% IgG2b, 10% IgG1, and 10% IgG3. Interestingly, the relative restriction of antichromatin autoantibodies to the IgG2a subclass was apparent in MRL/lpr mice as young as 1 month, well before the onset of lymphadenopathy. Antichromatin autoantibodies were also detectable in sera from MRL/Mp- +/+ (MRL/+), NZB, (NZB x NZW)F1 (B x W), and BXSB mice, but were not found in sera from normal mice. A similar subclass distribution skewed toward IgG2a was seen for MRL/+, B x W, and NZB mice. These results indicate that the spontaneous autoantibody directed against chromatin is a good marker for murine SLE, and is predominantly of the IgG2a subclass. PMID- 3338194 TI - The immunologic composition of neonatal milk: cellular components. AB - The cellular content of neonatal mammary gland secretions from 12 full-term infants less than 2 weeks postdelivery was studied. The predominant cell types observed were lymphocytes and macrophages with greater than 90% viability in each. The concentration of lymphocytes was significantly (P less than 0.001) correlated with the concentration of macrophages. The immunoglobulin content of this fluid was predominantly IgG with minimal concentrations of IgA, and no IgM detected. These data suggest both the presence of regulatory mechanisms for the cellular composition of neonatal breast secretions and that neonatal milk may bear a significant connection with the developing mucosal immune system. PMID- 3338195 TI - A high proportion of sera of heroin addicts possesses anti-HLA class I and class II reactivity. AB - The anti-HLA reactivity of sera from 210 heroin addicts was tested by the direct binding with 125I-labeled preparations of HLA class I and class II molecules purified from human B-cell lines of various HLA haplotypes. A high proportion (81.7%) of the sera tested possessed anti-HLA class I and II reactivity. The reactivity did not show any allospecificity and was apparently mediated by antibodies. The control included 100 healthy blood donors, 25 male homosexuals positive for anti-HIV (human immunodeficiency virus) antibodies, and 25 patients positive for HBsAg (hepatitis B surface antigen). Of these controls, only one of the healthy blood donors was positive for anti-HLA reactivity (P much less than 0.001). Among heroin addicts, the reactivity was independent of the presence of either HBsAg or anti-HIV antibodies in the serum. PMID- 3338197 TI - Role of nonspecific cytotoxic cells in intestinal epithelial cell injury in Nippostrongylus brasiliensis infection. AB - We have employed a cultured crypt-like intestinal epithelial rat cell line (IEC 18) to assess whether killing by nonspecific cytotoxic cells contributes to epithelial cell destruction in Nippostrongylus brasiliensis (N.b.) infection. Spleen cells from N.b.-infected Sprague-Dawley rats, 11-13 days postinfection when villus atrophy and crypt hyperplasia were evident, killed IEC-18 in a 4-hr 51Cr-release assay. In contrast, intraepithelial leukocytes (IEL) from N.b. infected rats showed decreased killing of IEC-18 compared to controls in a 16-hr assay. Spleen NK activity was increased in N.b.-infected rats whereas IEL NK activity was decreased. We conclude that direct cytotoxicity of crypt-like intestinal epithelial cells by nonspecific cytotoxic cells appears to play no significant role in intestinal injury in N.b. infection. PMID- 3338196 TI - Oligoclonality of rheumatoid factors arising spontaneously in lpr/lpr mice. AB - Rheumatoid factors (RF) from individual mice of the MRL/lpr and C3H/lpr strains were examined with regard to target specificity and heavy chain class expression. It was found that MRL/lpr-derived RF preferentially recognize IgG2a target antibodies while C3H/lpr-derived RF exhibit a broader range of cross-reactivity. IgM RF represent only a minor proportion of the RF response in both strains. The IgG2a-specific RF produced by the lpr strains were found to consist of relatively equal proportions of IgG1, IgG2b, IgG3, and IgA antibodies. However, most of the RF produced by a single individual expressed the same heavy chain class and antigen-binding specificity. These results indicate that within an individual lpr mouse, circulating RF are derived from extensive expansion of a limited number of antigen-activated precursors. PMID- 3338199 TI - New horizons in spinal surgery. PMID- 3338198 TI - Mononuclear cell-fibroblast interactions in scleroderma. AB - We studied cell proliferation and collagen biosynthesis in cocultures of dermal fibroblasts with peripheral blood mononuclear cells (MNC) from scleroderma patients and from age-matched normal controls. Autologous one-way mixed MNC fibroblast cultures revealed that fibroblasts do not stimulate MNC proliferation. Conversely, MNC stimulate autologous fibroblasts from scleroderma patients as well as from normal controls. This effect is increased in cells from scleroderma patients in which it seems to be mediated both by cell-to-cell interaction and through the production of soluble factors by MNC. In normal control cell systems we found no proliferative effect of supernatants of unstimulated cells or from those stimulated in autologous mixed-lymphocyte reactions. Coculture of fibroblasts with autologous MNC resulted in increased [14C]proline incorporation into both collagenic and noncollagenic proteins. This effect was mediated mostly by soluble factors that are released into the culture medium. Protein synthesis by MNC-fibroblast cocultures from scleroderma patients was significantly greater than protein synthesis by those from normal controls. Culture supernatants from unstimulated MNC or from autologous mixed-lymphocyte cultures caused a slight decrease in collagenic protein synthesis by cultured fibroblasts from scleroderma patients but not by those from normal controls. This effect of culture supernatants could be reproduced, and magnified, with purified IL-1 on cells from either patients or controls. Our findings indicate abnormal MNC-fibroblast interactions in scleroderma that could play an important role in the pathogenesis of fibrosis, the hallmark of this condition. PMID- 3338200 TI - New universal instrumentation in spinal surgery. AB - A new instrumentation for posterior spinal surgery consists of metallic rods carved with diamond-shaped asperities on which vertebral hooks or screws can be screwed in any position, level, or degree of rotation. The rods are interlocked by means of devices for transverse traction (DTTs), rectangular constructs with multiple vertebral grips, the stability of which allows suppression of any postoperative external support. Initially designed to treat scoliosis, this instrumentation design allows mobilization of the vertebrae located at the apex of the curve and obtains a three-dimensional correction. Correction of the areas of the most important structural deformation can also be obtained at the level of the end vertebrae, without any need to resort to an important distraction force. The technique varies according to the various types of curvatures. Approximately 250 patients were operated upon from 1983 to 1985. In idiopathic scoliotic curvatures, the mean percentage of correction was 66%. An important improvement of the associated sagittal deformations and of the apical derotation was observed in flexible curves. In paralytic curves, particularly with a pelvic obliquity, the percentage of correction of the frontal deformation is 77%. All of the spine patients were ambulatory in the first postoperative week, without any external support, and returned to their school or family activities. In 43 patients with follow-up periods longer than two years, there were no technical errors in 38. The final angular loss of correction was less than 2 degrees in the error-free group. PMID- 3338201 TI - Mechanical testing of spinal instrumentation. AB - Clinically, implant failure is often the result of fatigue from continuous cyclic loading. Because of the inadequacies of long-run cyclic testing, fatigue susceptibility of implants was investigated by means of strain measurements and stress analysis under physiologic loads. The implants were equipped with strain gauges during load-deformation testing, and the tensile stress (the component of stress-producing fatigue failure in metals) was calculated for that site on the implant. For metals most often implanted for spinal surgery, such as stainless steel and chrome-cobalt alloys, a stress exists, known as the endurance limit, below which failure will not occur, even if cycled indefinitely. By calculating the tensile stresses in an implant and relating them to the endurance limit, the implant's susceptibility to fatigue can be determined at the site of stress analysis without formal cyclic load testing. PMID- 3338202 TI - The posterior tether in scoliosis. AB - The hypothesis that a localized lordosis, or tethering of the posterior elements of the spine, is the primary cause of the vertebral rotation in idiopathic scoliosis was investigated in anatomic specimens of human and calf spinal columns. The specimens were axially loaded with and without a posterior tether created using Zielke instrumentation. Lateral deflection and axial rotation were monitored roentgenographically. The vertebrae of tethered spines showed increased rotation in the direction associated with idiopathic scoliosis. The spinous processes moved toward the concavity at the apex of the induced lateral curve. Conversely, untethered spines either exhibited little rotation or rotated in the opposite direction; the spinous processes moved toward the convexity of the curve. Rotations toward the convexity occur in rotational kyphosis. Thus the hypothesis that idiopathic scoliosis is a rotational lordosis is substantiated; the characteristic rotation can be explained with the aid of a geometric model. PMID- 3338203 TI - A contoured anterior spinal fixation plate. AB - There is a need for a specifically designed plate for anterior fixation of the vertebral bodies, contoured to fit closely around the lateral aspect of the spine and wide enough to allow multiple options for placement of at least three screws in each vertebra. The large-diameter cancellous screws should penetrate the opposite cortex. Existing bone plates are inadequate, because they are too narrow and do not allow positioning of more than two screws in each vertebra. The Biomedical Engineering Department of the National Research Council of Canada designed and tested the plate described in this article, with particular attention to providing smooth surfaces to prevent vascular complications. Three lengths of plates have been developed and are used in the area from T11 to L5, with a specific tapered plate for the L5 area to prevent contact with the overlying iliac vessels. This device should be used for stabilization following corpectomy for tumor, decompression of burst fractures, severe disc degeneration, pseudarthrosis, and the multiply operated back. PMID- 3338204 TI - Computed tomography evaluation of stability in posterior fracture dislocation of the hip. AB - Measurements of the percentage of remaining posterior acetabulum on computed tomography (CT) scan (the Acetabular Fracture Index) in posterior fracture dislocations of the hip were evaluated to determine the stability of the joint. All hips with less than 34% of the remaining posterior acetabulum were unstable. Hips with greater than 55% were stable. Between these values, hips were either stable or unstable. A statistical analysis demonstrated highly significant differences in the average remaining posterior acetabulum between the stable and unstable group. These findings were based on a review of 26 patients with posterior fracture dislocations of the hip (Epstein Type I-IV injuries) combined with CT scan analysis. The clinical status of hip stability was correlated with the Acetabular Fracture Index, and this provided the basis for the study. A simple linear measurement of the remaining posterior acetabulum on CT (the Approximate Acetabular Fracture Index) can be done easily by a physician, and this closely approximates the true remaining acetabular arc. Seven of ten unstable hips in 31 Epstein Type I-V patients showed femoral head subluxation of 0.5 mm or more on CT scan, whereas none of the 21 stable hips had demonstrable subluxation. Risk analysis provided a means of predicting hip stability for individual patients. PMID- 3338205 TI - Charnley arthroplasty in osteoarthritis secondary to congenital dislocation or subluxation of the hip. AB - A follow-up study was made on 129 consecutive Charnley arthroplasties in osteoarthritis secondary to congenital dislocation of the hip. The acetabular component was placed as far distal as possible using a standard technique. Bone grafting was not performed. The survival of the prostheses was assessed by the survivorship method. The cumulative survival rate of the prostheses was 93% after five years, 89% after ten years, and 80% after 15 years. In 77% of the cases the acetabular component had been placed in the true acetabulum or levels the rate of mechanical loosening of the acetabular levels the rate of mechanical loosening of the acetabular component (revisions and acetabular components showing a radiolucent line of increasing width) was 13% compared with 42% in the group where the acetabular component was placed proximal to the roof of the true acetabulum (p less than 0.005). PMID- 3338207 TI - Flexible intramedullary fixation of femoral fractures. AB - Fifty femoral fractures in 47 patients were treated by the insertion of flexible intramedullary Ender rods and observed until fracture healing was complete. Both condylocephalic and trochanteric approaches were used with a preference for the latter when biomechanically feasible. The fractures ranged from the intertrochanteric-subtrochanteric junction to the supracondylar area of the femur. This technique can be used to treat fractures unsuited for conventional rods. The system is relatively uncomplicated, the technique atraumatic. Healing is generally rapid. There were no non-unions, infections, surgical deaths, or significant residual deformities. PMID- 3338206 TI - Trochanteric osteotomy for revision total hip arthroplasty. 97% union rate using a comprehensive approach. AB - In current practice most primary total hip arthroplasties (THAs) are performed without trochanteric osteotomy. The superior exposure afforded by trochanteric osteotomy, however, can be valuable in revision total hip surgery. Between 1969 and 1983, 188 revisions in 177 patients were carried out with osteotomy of the greater trochanter. Ninety-one percent were reattached with a three- or four-wire method. Sixty-one percent of the trochanters (N = 114) were advanced to the lateral cortex. Supplemental trochanteric mesh was used in 75% of the revisions (141 hips). Its use is now routine for all revisions. Most patients (N = 137) were permitted to ambulate within five days, using a walker or two crutches, bearing partial weight on the operative hip. Ninety-seven percent (182 of 188) of the trochanters united. Six failed to unite (3%) and eight others had delayed healing (4%). Two trochanters migrated proximally prior to union (1%). Retrospective evaluation of the initial postoperative radiographs for each patient with nonunion identified one or more technical errors in the reattachment technique. While the overall incidence of wire breakage was 27%, most (42 of 51) of these trochanters healed uneventfully. Five of the six patients with trochanteric nonunion, however, had failure of one or both vertical wires by 12 weeks after surgery. The average hip score for the patients with nonunion was 89 points (versus 57 points before surgery), indicating that the average clinical outcome in this group was not substantially comprised by trochanteric complications. In light of the improvement in surgical exposure, high rate of union of the trochanter, and limited number of complications, trochanteric osteotomy is recommended for most revision THA. PMID- 3338208 TI - Recurrent dislocations and subluxations of the patella. AB - Seventy-four patients with patellar dislocations and subluxations were treated with a procedure described by Trillat. The Trillat method consists of stepwise correction of predisposing anatomic abnormalities including lateral retinacular release, patellar tubercle transfer, and advancement of the vastus medialis, if necessary. The follow-up period in 42 knees was from two to nine years with an average of 4.2 years. The results were excellent in six knees, good in 28 knees, fair in five knees, and poor in three knees. Thorough intraarticular examination is essential. If significant patellofemoral arthritis is present, a Maquet procedure should be performed. PMID- 3338209 TI - Considerations in total knee arthroplasty following previous knee fusion. AB - Two patients who were dissatisfied with the functional results of knee fusion had conversion to total knee arthroplasty at one and 16 years following previously solid fusion. Both patients were over 65 years of age. Unconstrained prosthetic components were used and no special soft tissue stabilizing procedures were needed. At follow-up examinations, five and one-half and three years postoperatively, the results have been gratifying with good stability and adequate range of motion from 0 degrees to 90 degrees of flexion. Both patients were able to walk and climb stairs without support. The patients claimed that quality of function was significantly improved. Whenever possible, fusion of the knee in young people should be done so that this option remains open in later life. Arthrodesis is advised in young patients to allow for possibility of revision to total knee arthroplasty at a later date as technology improves. PMID- 3338210 TI - A clinical and radiographical analysis of 127 anterior cruciate insufficient knees. AB - The progression from chronic anterior cruciate instability to degeneration of the knee has been well documented in animal studies. However, the literature is unclear as to the overall consequences with respect to the development of osteoarthritis. The long-term consequences of the anterior cruciate insufficient knee with or without associated medial collateral ligament insufficiency was investigated in 127 consecutive patients. The effects of meniscal injury and/or meniscectomy in the presence of ligamentous insufficiency was correlated with roentgenographic observations. A scoring system was devised and found to show that anterior cruciate insufficiency naturally progresses toward degenerative osteoarthritis. Meniscectomy with and without an associated medial collateral ligament insufficiency hastens the degenerative process. Progressive functional deterioration was shown to correlate with roentgenographic evidence of degenerative changes. The ultimate success of surgical repairs and reconstructions of the anterior cruciate ligament will not be based only upon functional return to activity or objective stability, but will also depend on the procedure's ability to prevent later development of degenerative osteoarthritis. PMID- 3338211 TI - Acute anterior cruciate ligament repair. AB - Sixty-six consecutive patients with acute repair of a complete isolated anterior cruciate ligament (ACL) injury were retrospectively reviewed to evaluate the effectiveness of the authors' surgical technique. All patients noted either a pop, acute swelling, or had acute disability after injury with 58% experiencing all three signs and symptoms. Preoperative testing without anesthesia revealed 95% of patients to have either a positive modified Losee or Lachman test. Postoperative results were obtained by questionnaire in 41 of 42 patients (98%) with a minimum two-year follow-up period. Physical examination was completed in 32 (76%) and arthrometer testing in 30 (71%) patients. Subjective results were good or better in 91%. No patients had buckling or meniscal loss postoperatively. Patellofemoral pain, however, was significant in 15% and severe in 2%. Postoperative functional results were good or better in 78% with all patients participating in sports, 76% in "at risk" sports. A Performance Quotient (P.Q.) was developed to more accurately correlate preinjury and postoperative function. The average P.Q. was 0.87. Objective results were good or better in 100%. Stability was within normal limits by clinical observation in 88%, and by arthrometer testing in 87%. ACL repair is recommended in the young patient who is active in "at risk" sports and who is unwilling to modify activities and willing to undergo a one-year rehabilitation period. PMID- 3338212 TI - Cotrel-Dubousset instrumentation in idiopathic scoliosis. A preliminary report. AB - This is a preliminary report on Cotrel-Dubousset (CD) instrumentation for the surgical management of idiopathic thoracic scoliosis. From September 1985 through April 1986, 37 patients were treated at the authors' hospital, by posterior spinal fusion with CD instrumentation. Twelve patients had surgical treatment of spinal deformity associated with other disorders or had revision surgery. The remaining 25 patients, with no prior surgery, were diagnosed as having juvenile or adolescent idiopathic scoliosis. After operation, this group of patients was routinely noted to have significant improvement in rib deformity. This is associated with the rotational correction achieved with CD instrumentation and contrasts with the minimal rib deformity correction with Harrington instrumentation documented by some workers. In this series, no rib resections have been necessary in conjunction with CD instrumentation. No postoperative external immobilization was used. Ambulation began on the second postoperative day, and patients were discharged five to seven days after operation. Gradual resumption of normal activities was allowed at six weeks, and full activities, other than contact sports, after three months. PMID- 3338213 TI - Complex fracture-dislocation of the metacarpophalangeal joint. Case report. AB - A complex fracture-dislocation involving the fifth metacarpophalangeal (MCP) joint occurred in a 16-year-old boy approaching skeletal maturity. Roentgenographic examination demonstrated a widened MCP joint and a dorsally displaced Salter-Harris Type III fracture of the metacarpal head. Attempted manipulative closed reduction was unsuccessful. To achieve successful reduction and fixation it was necessary to make a dorsal approach, incise the interposed volar plate longitudinally, and lever it to the anatomic volar position. Successful fixation of the fracture would have been impossible through a volar approach. The Salter-Harris Type III fracture is a surgical problem. PMID- 3338214 TI - Os peroneum fracture. A case report. AB - A 40-year-old woman with a history of injury to the left foot was initially treated for an ankle sprain. When the initial roentgenograms were reassessed, os peroneum fracture with diastasis was diagnosed. This may be the second case of fracture of the uncommon anomaly to be reported in the literature. A fracture of the os peroneum may be confused with ankle sprain. Only careful examination of serial roentgenograms may avoid an incorrect diagnosis and further complications. PMID- 3338215 TI - Bovine bone morphogenetic protein (bBMP) induced repair of skull trephine defects in sheep. AB - An aggregate of partially purified bovine bone morphogenetic protein (bBMP) and bone matrix insoluble noncollagenous proteins (iNCP), weighing a total of 100 mg of lyophilized BMP/iNCP, was implanted using ultra thin gelatin capsules in skull trephine defects in adult sheep. One hundred milligram samples of freeze-dried bovine serum albumin (BSA) were similarly implanted for controls. In five sheep, the capsules were implanted in 18-20 mm trephine skull defects and also in posterior cervical muscle pouches for heterotopic controls. In two out of five sheep, the trephines were repaired with bone as early as four weeks after the operation. Eight to 12 weeks after surgery repair was complete in the other three sheep. In the control contralateral trephines, one-third to one-half of the defect was incompletely repaired. Neither the BMP nor the BSA control implants induced bone formation in the muscle. While the BMP/iNCP prepared from bovine bone consistently induced regeneration in skull trephine defects, only fibrous tissue and no extraskeletal bone was induced to form in cervical muscle pouches in sheep. PMID- 3338216 TI - An examination of the mechanism of ligament contracture. AB - It has been proposed that the mechanism of ligament contraction involves conversion of fibroblasts to a contractile form similar to the phenomenon recently documented in wound contraction. In this study rat knees were surgically immobilized in flexion and a sham operation was performed on the contralateral knees. Mechanical studies revealed that the flexion contracture increased rapidly for two weeks. The anterior cruciate ligaments (ACL) were contracted and contributed to the flexion contractures. Histologic studies of the ACL showed no increase in the cellularity of the contracted ligaments. In the contracted ligaments, staining for the contractile protein actin was heavy. Previous transmission electron microscopy studies have demonstrated fibroblast cytoplasm in processes far from the visible cell body and it is hypothesized that this cytoplasm was responsible for increased actin staining away from the visible cell body. This study supports the concept that ligament fibroblasts, modulated to a form containing increased quantities of the contractile protein actin, play an active role in the contraction of ligamentous tissue. PMID- 3338217 TI - Bone mineral content and mechanical strength. An ex vivo study on human femora at autopsy. AB - Bone mineral content as determined by computed tomography (CT) and mechanical strength on axial loading were compared in 36 cadaveric femur specimens. In axial loading, 34 femora fractured vertically in the neck, one femur fractured subtrochanterically, and one in the shaft. Based on the CT measurements of density and area, the mass of a transverse slice of the femur was estimated. Highly significant correlations were demonstrated between strength and cancellous bone density. Even higher correlations were revealed when the bone masses of the proximal and distal femoral areas were calculated. Based on these findings, an equal distribution of the effective mass of the femur was postulated. PMID- 3338219 TI - The internal skeletal fixation system. A new treatment of thoracolumbar fractures and other spinal disorders. AB - A new internal skeletal fixation system (ISFS) for stabilizing thoracolumbar fractures and other spinal disorders was developed by Dick in Switzerland. The ISFS is a modification of the Magerl external skeletal fixation system of the spine. The Dick modification consists of a threaded rod connected by clamps to Schanz screws and is located in the vertebral pedicles on both sides of the spine. Due to a stable angle between the rod and Schanz screw, a one-point fixation above and below the diseased vertebra is sufficient. The ISFS provides a short fixation and promotes fusion. Control of lordosis, kyphosis, and rotation of the spine is possible with threaded rod distraction and compression and through manipulation of the Schanz screws held by movable clamps. The advantage of the ISFS is the ability to achieve reduction and fixation with the same instrumentation. ISFS has been used in more than 90 patients and proven most adequate for thoracolumbar fractures and other localized spinal disorders. The Harrington system and its modifications are no longer in use for these problems. PMID- 3338218 TI - Meniscal regeneration and its effects on articular cartilage in rabbit knees. AB - The incidence and size of meniscal regeneration after medial meniscectomy on the right knee and lateral meniscectomy on the left knee of 44 rabbits was observed and correlated with development of degenerative arthritis. Complete meniscal regeneration was found in 23% of medial meniscectomy knees, partial regeneration in 68%, and no regeneration in 9%. Among 44 lateral meniscectomies, only 5% had complete meniscal regeneration, and 68% had no meniscal regeneration. The remaining 27% of knees had partial regeneration. Degenerative changes of articular cartilage in the tibiofemoral joints of all knees were inversely correlated with the size of the regenerated meniscus. These observations suggest that poor results following lateral meniscectomy may be due to a lower level of meniscal regeneration and relatively poor morphological regeneration of the lateral meniscus compared to the medial meniscus. PMID- 3338220 TI - Massive solitary tophus containing calcium pyrophosphate dihydrate crystals at the acromioclavicular joint. AB - A massive solitary tophus containing calcium pyrophosphate dihydrate (CPPD) crystals was resected from the distal clavicle and proximal acromion of a 62-year old man who presented with a painful shoulder mass. The diagnosis was confirmed histologically and by X-ray diffraction. CPPD crystal deposition was found within bone, however, the articular cartilage was not involved. Other unusual features of the case include the size of the lesion, the monoarticular presentation and a peculiar discoloration of the overlying skin. The clinical presentation and radiographic features were initially consistent with a malignant process; thus the case demonstrates that CPPD arthropathy should be included in the differential diagnosis of periarticular tumors. PMID- 3338221 TI - Diaphyseal intraosseous ganglion. AB - Ganglion cysts of bone are noted to occur most often in the metaphysis of epiphysis of a long bone. A unique ganglion cyst, developing in a diaphyseal location, was excised from the leg of a 14-year-old boy. The follow-up examination showed no recurrence one year following surgery. PMID- 3338222 TI - Transpedicular fixation of thoracolumbar vertebral fractures. AB - The most frequent surgical treatment of thoracolumbar fractures is still the Harrington rod system despite some adverse effects, the most serious being the locking of five to seven segments. The new pedicular fixation modifications suggested by Magerl and Dick lock only two segments and give far better stability of the fractures. Used internally, the system is convenient for the patient, permitting early mobilization, often without any external support. The instrument, called the "posterior segmental fixator" (PSF), is used both as a reduction device and as a fixation device. The injured vertebra is grafted through the pedicle, giving security against late collapse after device removal. Twenty patients treated with this method had an average follow-up period of ten months. The primary reduction attains 88% of the calculated height of the injured vertebra, with only a few percent loss during follow-up time. Clearance of fragments in the spinal canal, diagnosed with computed tomography scan in eight patients, was successfully accomplished in all but one, with only distraction or reduction of the fragment through a limited laminotomy. The instrumentation in these cases was lateral to the dura. Nine patients with neurologic deficits improved and could walk without support or with crutches within a few months. One patient with complete paraplegia remained unchanged. PMID- 3338223 TI - Flexion-distraction injuries of the lumbar spine. Mechanisms of injury and classification. AB - This paper describes the fracture patterns in 20 patients with flexion distraction injuries. A mechanism of injury is described that includes an explanation of the presence of wedge compression fractures and burst injuries. A classification is developed based on trauma to the anterior vertebral column, the posterior elements, and the resulting axially loaded spine. PMID- 3338224 TI - Sacral fractures: an important problem. Retrospective analysis of 236 cases. AB - Sacral fractures, often undiagnosed and untreated, frequently result in neurologic symptoms and deficits to the lower extremities and urinary, rectal, and sexual dysfunctions. These same neurologic problems often remain the major chronic sequelae after the more obvious pelvic trauma lesion has healed. Specific treatments aimed at neurologic problems are available and may allow the patient functional recovery. This is illustrated by anatomic observations on the sacrum in 39 cadavers showing the relationship among sacral nerve roots within their foramina. These observations were valuable for a retrospective study of 236 consecutive patients with sacral fractures in a series of 776 patients with pelvic injuries. A new classification of sacral fractures evolved from this study and provided a better understanding of the mechanisms responsible for the associated neurologic symptoms. The classification is based on the direction, location, and level of sacral fractures. Three different zones were identified as having characteristic clinical presentations: Zone I, the region of the ala, was occasionally associated with partial damage to the fifth lumbar root. Zone II, the region of the sacral foramina, is frequently associated with sciatica but rarely with bladder dysfunction. Zone III, the region of the central sacral canal, is frequently associated with saddle anesthesia and loss of sphincter function. Routine pelvic roentgenograms were almost useless in identifying the pathologic process in sacral injuries with neurologic symptoms. Ferguson views, tomograms, and particularly computed tomography scans were crucial for understanding these injuries. Cystometrography was most helpful in positively identifying fractures causing neurogenic bladders. Cystometrograms should be ordered routinely in Zone III injuries. Preliminary observations suggest that surgical decompression permitted significantly better neurologic recovery than nonsurgical methods. PMID- 3338225 TI - Reduction and stabilization of grade IV spondylolisthesis. AB - Virtually any degree of spondylolisthesis can be reduced and held using variable screw placement (VSP) slotted plates and transpedicular screws. All of the soft tissue holding the displaced vertebrae must be stretched prior to pulling the vertebrae back into normal alignment. Complete control of the displaced vertebrae is gained through the transpedicular screws, and fixation is accomplished by bolting the screws to the spine plates that have been bent to achieve the proper lumbar lordosis. Ultimate stability is gained by both a bilateral lateral and interbody fusion. PMID- 3338227 TI - Posterior lumbar interbody fusion and plates. AB - Posterior lumbar interbody fusion (PLIF) is accepted by many authors as the surgical treatment for herniated discs, degenerative disc conditions, and Grades I and II spondylolistheses. PLIF is now used in conjunction with newly developed segmental spine plates by using transpedicular screw fixation to enhance the osteosynthesis and success rate of interbody fusion. To date, 104 fusions have been performed in 67 patients with no dislocations of any interbody grafts and no indication of absorption, pseudoarthrosis, or infections. PMID- 3338226 TI - Degenerative spondylolisthesis. Pathophysiology and results of anterior interbody fusion. AB - With special attention to the articular facets, an inspection of dry human spinal columns, microradiographic studies of cadaveric specimens, and animal experiments revealed that development of degenerative spondylolisthesis is attributable to rotational strain on the facetal joints at the level of involvement. Disc degeneration predisposes to intersegmental instability and rotational strain, which result in secondary osteoarthritic change of the articular processes and segmental canal stenosis. Thirty-six patients with degenerative spondylolisthesis were treated with anterior interbody fusion (AIF) for segmental canal stenosis at the authors' hospital during 1958-1985. The surgical results of these patients reveal that AIF corrects malalignment of the lumbar spine by complete discectomy, reduces the slip and restores the disc height, and resolves nerve compression, both from the front and from behind, by enlargement of the stenosing canal. In addition, AIF has consistent and satisfactory clinical results at long-term follow-up evaluation because it resolves intersegmental instability, an important problem of degenerative spondylolisthesis. AIF is a reasonable and reliable treatment for patients younger than 60 years of age with segmental stenosis. PMID- 3338228 TI - Dermatology training during the pediatric residency. AB - The diagnosis and treatment of disorders of the skin and subcutaneous tissue represents a significant aspect of general pediatric practice. A study was carried out to assess the status of training in dermatology among residents in pediatrics. Sixty five pediatric residents in seven different training programs were asked to identify color transparencies of 20 common dermatoses. Their mean score of 53.2 percent was considerably lower than that of an equivalent group of residents in dermatology (86.4%). A survey of pediatric residencies throughout the United States indicated that 67 percent of those responding offer an elective in pediatric dermatology. PMID- 3338229 TI - Severe obstructive sleep apnea in a child with osteopetrosis. AB - The clinical features of a 5-year-old patient with osteopetrosis and severe obstructive sleep apnea are presented. The patient responded to tonsillectomy, adenoidectomy, uvulectomy, and tracheostomy. The tracheostomy was later removed. Osteopetrosis, while rare, may be added to the list of causes of obstructive sleep apnea. PMID- 3338230 TI - Long-term prognosis for children with nephrotic syndrome. AB - Follow-up survival and health information were obtained, after a median of 27.5 years, from 132 patients who had been seen originally as children with nephrotic syndrome between 1951 and 1967. Ninety seven patients were alive. Recurring edema or proteinuria, or both, persisted in 15 percent of those still alive. Eight of 11 parous women reported relapses during pregnancy. There was no apparent increase in malignancies, atopic diseases, clinical defects in cell-mediated immunity, or cardiovascular diseases. Twenty two patients (17%) died of renal causes between 3 months and 8 years after the onset of nephrotic syndrome. Steroid resistance was the presenting feature universally predictive of a poor outcome; nine of the 11 such patients died and the other two are now receiving hemodialysis. Hematuria was present initially in 41 percent of the patients who died of renal causes, compared with 14 percent of those still alive. Hypertension was noted on the first examination in 22 percent of those who died of renal causes, compared with 10 percent of those alive. PMID- 3338231 TI - Hallucinogenic mushrooms. AB - Ingestion of mushrooms containing psilocybin produces hallucinogenic effects and has become a popular form of substance abuse among some adolescents and young adults. We have reviewed the medical literature on psilocybin mushrooms and describe current patterns of use, provide background material on the botony and pharmacology of these crude drugs, and report results of a small study on usage patterns among identified adolescent drug abusers. Among 174 adolescents already identified as substance abusers, 45 (26%) reported having used hallucinogenic mushrooms, frequently in conjunction with alcohol or other drugs. An average intake of 2-4 mushrooms was obtained for about +8, and led to intoxication for 5 6 hours. Mixing of intoxicants such as alcohol, marijuana, and psilocybin mushrooms was the rule. The acute adverse reactions may have been the result of drug synergy. Pediatricians should become aware of the specific patterns of the use of hallucinogenic drugs by adolescents and consider the possibility of such use when evaluating a delirious or psychotic adolescent. PMID- 3338232 TI - A controlled trial of methylphenidate in black adolescents. Attentional, behavioral, and physiological effects. AB - The short-term effects of methylphenidate were examined on behavioral, laboratory, academic, and physiological measures in 11 black male adolescents diagnosed as having attention deficit disorder (ADD). In a double-blind, crossover design with randomized order, the subjects received placebo and each of three methylphenidate doses (0.15 mg/kg, 0.30 mg/kg, and 0.50 mg/kg) for a period of 2 weeks per medication dosage. Significant drug effects were found for the majority of measures. In general, the higher doses resulted in the most beneficial response in behavioral, academic, and laboratory measures of attention and impulsivity. However, a significant linear increase occurred in diastolic blood pressure. The results suggest that methylphenidate is an effective adjunct to the treatment of ADD in adolescents. PMID- 3338234 TI - Consent in diagnostic radiology. PMID- 3338233 TI - American Society for Clinical Pharmacology and Therapeutics. Abstracts of papers. Eighty-ninth Annual Meeting, March 9-11, 1988, San Diego, California. PMID- 3338235 TI - Low osmolar contrast media. PMID- 3338236 TI - Population screening by mammography. PMID- 3338238 TI - The distribution of pulmonary shadowing in farmer's lung. AB - Reports of the radiological features in farmer's lung are inconsistent. We have reviewed clinical and radiological findings in eight patients with farmer's lung in the acute and sub-acute phases. In the acute phase the main feature is transient widespread diffuse shadowing of air space consolidation. In the sub acute phase, the predominant feature is fine nodular shadowing tending to involve either the upper half or upper two-thirds of the lungs with relative sparing of the basal segments. This is in accordance with both the pathophysiological behaviour of the inhaled particulate antigen and the subsequent distribution of pulmonary changes in chronic farmer's lung. PMID- 3338237 TI - Scimitar etcetera--the dysmorphic right lung. AB - 'Dysmorphic lung' is introduced as a term to describe any complex congenital malformation which involves both abnormal vascular morphology and disordered growth of a whole lung. The major group within this definition is the scimitar syndrome, which we choose to mean a hypoplastic lung with anomalous venous drainage and various degrees of collateral arterial supply. Nine typical cases of scimitar are presented, with three closely related cases. Six other cases of dysmorphic lungs are also present. The relationships between the groups are discussed, and an effort is made to clarify the nomenclature used in this condition. PMID- 3338239 TI - The plain chest radiograph after acute smoke inhalation. AB - Serial chest radiographs of 45 patients from a major fire disaster were assessed for the effects of smoke inhalation injury. Thirty-three had abnormal chest radiographs on admission. Bronchial wall thickening was present in a total of 29 patients, subglottic oedema in 13, pulmonary oedema in seven, and patchy consolidation in three. Seven patients developed pulmonary oedema following initial exposure. This was the cause of death in two patients. Serial chest radiographs were useful in monitoring this very severe complication. Bronchial wall thickening and subglottic oedema were common early findings and thus may herald more serious subsequent respiratory embarrassment. Subglottic oedema is a previously undescribed finding. It not only indicates damage to the upper airways but may also indicate damage to the lung parenchyma. It may also make endotracheal intubation difficult. Therefore, the initial chest radiograph is an important predictor of significant smoke inhalation injuries enabling selection of patients likely to need ventilatory support. PMID- 3338240 TI - The chest radiograph in brucellosis. AB - A retrospective study of chest radiographs in patients with brucellosis was undertaken at King Khalid University Hospital, Riyadh. The commonest presenting symptoms were fever, back and joint pains, excessive sweating, headache, and cough. Different chest radiographic abnormalities were detected, including soft miliary mottling, parenchymal nodules, consolidation, chronic diffuse changes, hilar or paratracheal lymphadenopathy and pneumothorax. Soft miliary mottling and pneumothorax have not been described before. The high incidence of lung abnormalities is most probably due to the chronicity of the disease in the present series. PMID- 3338241 TI - Paget's disease of bone in South Africa. AB - A survey of Paget's disease of bone in Johannesburg South Africa, has revealed a prevalence of 2.4% in whites aged 55 years and over, which is similar to some centres in Europe; it has also revealed an unexpectedly high prevalence of 1.3% among blacks. These findings are discussed in relation to recent concepts of the pathogenesis of Paget's disease. PMID- 3338242 TI - Intravertebral vacuum phenomenon. AB - Intraosseous gas formation may occasionally be seen within vertebral crush fractures after spinal osteoporosis. This is due to a vacuum phenomenon which follows impaired fracture healing and may be related to avascular necrosis. Four cases are reported from rural Thailand. A high incidence may reflect inappropriate steroid therapy. PMID- 3338243 TI - Temporomandibular joint arthrography: dynamic study by videorecording. AB - Temporomandibular joint symptoms are common. Patients not successfully treated by conservative methods require accurate assessment of the internal derangements of the joint. Temporomandibular joint arthrography using only videorecorded intensifier fluorography displays the anatomy and function accurately with a low radiation dose. PMID- 3338245 TI - The value of pre-operative intracavitary radiotherapy in patients treated by radical hysterectomy and pelvic lymphadenectomy for invasive carcinoma of the cervix. AB - Two hundred and twenty-four patients with invasive carcinoma of the cervix treated by radical surgery have been studied retrospectively to determine the impact of pre-operative intracavitary radiotherapy. Pre-operative radiotherapy made no difference to survival, the incidence of local recurrence, distant metastasis or complications. PMID- 3338244 TI - Barium enemas are a headache. AB - The frequency of headache after Picolax (sodium picosulphate, Nordic Ltd) preparation for barium enema was investigated and its association with dehydration, as assessed by haemoconcentration, was determined. Eleven out of 41 patients (26.8%) complained specifically of headaches. Although patients with and without headaches developed significant increases in haemoglobin concentration after Picolax preparation, the rise in haemoglobin in those with headaches was significantly greater than in those without (P less than 0.05). In both groups the haemoglobin concentration returned to normal after a bowel washout. These results suggest an association between dehydration and headache developing after a Picolax regimen. It may be possible to prevent this symptom by advising on the intake of specific volumes of fluid during preparation for barium enema. PMID- 3338248 TI - A century of science for health. PMID- 3338246 TI - An unusual appearance of a left adrenal mass on computed tomography. AB - A case of carcinoma of the left adrenal gland in which computed tomography (CT) demonstrated posterior displacement of the splenic vessels and tail of the pancreas is reported. PMID- 3338247 TI - Education for clinical research: an experiment at the University of Michigan. PMID- 3338249 TI - Relationship between glomerular filtration rate and renal blood flow at different levels of protein-induced hyperfiltration in man. AB - 1. We studied the relationship between changes in glomerular filtration rate (GFR) determined as inulin clearance (CIn), and changes in renal blood flow (RBF), determined as p-aminohippurate clearance (CPAH), after the ingestion of a large (1.35 +/- SEM 0.04 g/kg, n = 9), moderate (1.08 +/- 0.03 g/kg, n = 10) or mild (0.55 +/- 0.02 g/kg, n = 8) protein load given as a meat meal. Control subjects (n = 10) received a carbohydrate meal. 2. CIn and CPAH increased after a protein meal. Two hours after eating the test meal, GFR levels were (mean +/- SEM) 160.0 +/- 13.8 (P less than 0.05), 141 +/- 7.69 and 127.8 +/- 9.07 ml/min in the groups that received a large, moderate and mild protein load, respectively. Peak CIn values after the meal were 211.6 +/- SEM 14.92 (P less than 0.001), 177.5 +/- 10.88 (P less than 0.01) and 129.0 +/- 8.72 ml/min after a large, moderate and mild protein load, respectively. 3. At peak GFR levels after the meal, filtration fraction (FF) (CIn X 100/CPAH) increased significantly (P less than 0.02) with the large and with the moderate protein load, but not with the mild protein load. 4. There was a significant (P less than 0.001) positive relationship between increments of FF and increments of CIn, but not CPAH, whether the values were expressed as post-meal/pre-meal ratios or as absolute changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338250 TI - Cardiovascular responses to upright tilting in healthy subjects. AB - 1. The cardiovascular responses to passive upright tilting were determined in healthy human subjects of various ages using entirely 'non-invasive' techniques. Cardiac output was determined by a single breath method and arterial blood pressure by an automatic sphygmomanometer. 2. Steady-state responses were achieved within 4-6 min from the onset of the tilt and were maintained for at least 15 min. 3. The reproducibilities of the responses to tilting by 60 degrees, expressed as two standard deviations of the differences between responses on two occasions (mean responses in parentheses), were: cardiac output +/- 0.70 (-1.41) litre/min, heart rate +/- 7.6 (+14.7) beats/min, systolic blood pressure +/- 15.5 (+1.0), and diastolic blood pressure +/- 13.1 (+13.6) mmHg. 4. Tilting by 20 degrees resulted in no significant responses but between 20 degrees and 60 degrees responses were linearly related to the angle of tilt. 5. Supine values and responses to tilting by 60 degrees were compared in subjects in four age groups between 20 and 80 years. With increasing age, the supine values of cardiac output declined and those of arterial blood pressures increased. Responses of heart rate, cardiac output and diastolic pressure declined by increasing age. These results, obtained from a healthy population, provide reference values for comparison with individuals who may have deficient postural responses. PMID- 3338251 TI - Alveolar carbon monoxide: a comparison of methods of measurement and a study of the effect of change in body posture. AB - 1. We have compared rebreathing, breath-hold and mean alveolar methods of measuring alveolar carbon monoxide (CO), at levels similar to those found in smokers, as a preliminary to using them as indirect measures of carboxyhaemoglobin levels. In the present study alveolar CO levels were raised by rebreathing a 2% CO mixture. 2. Breath-hold CO was measured after breath-hold times of 0-35 s in 5 s increments. Using generalized linear models, the maximum value for breath-hold CO was estimated to occur at 23 s. Breath-hold CO after a 20 and 25 s breath-hold were similar to and significantly greater than those of less than 20 s or greater than 25 s. 3. As expired CO increased, the difference between breath-hold and mean alveolar CO became proportionally larger. On average, breath-hold CO was 24% larger than mean alveolar CO. 4. Rebreathing, breath-hold and mean alveolar CO were compared at four different inspired oxygen concentrations. Expired CO increased significantly with increasing oxygen for all three methods. At end-tidal oxygen levels of less than 25%, breath-hold and rebreathing CO were similar, however, the overall mean difference between the three methods was significant. 5. While rebreathing CO was unaffected by changes in ventilation/perfusion of the lung, induced by change in body posture, both breath-hold and mean alveolar CO showed a significant fall with change from the supine to erect posture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338252 TI - Is alveolar carbon monoxide an unreliable index of carboxyhaemoglobin changes during smoking in man? AB - 1. We measured alveolar carbon monoxide (CO) after a 20 s breath-holding period and carboxyhaemoglobin both before and after smoking a cigarette on 500 occasions (101 individuals). The two measurements were closely correlated but there was a marked difference in the change or 'boost' after smoking one cigarette. The mean relative boosts ([post value--pre value]/[pre+post]/2) for alveolar CO and carboxyhaemoglobin were 7.7% and 20.3%, while negative boosts (fall rather than the expected rise) were seen in 103 of 500 and three of 500 occasions respectively. In 140 studies a third alveolar CO reading taken 5 min later was slightly larger, but the difference was insignificant. 2. In seven subjects where the carboxyhaemoglobin level was raised by breathing a 2% CO gas mixture, the alveolar CO and carboxyhaemoglobin boosts were similar (71.7% and 75.2% respectively), and they fell sharply subsequently rather than increasing further as occurred after smoking. 3. We conclude that alveolar CO measurements give a useful estimate of carboxyhaemoglobin level if the subject has not smoked for at least half an hour but that measurements of alveolar CO boost are useless since the act of smoking interferes with alveolar sampling. We postulate that cigarette smoking induces a transient change in pulmonary gas exchange. PMID- 3338253 TI - Degradation by bacterial enzymes of colonic mucus from normal subjects and patients with inflammatory bowel disease: the role of sialic acid metabolism and the detection of a novel O-acetylsialic acid esterase. AB - 1. The activities of enzymes degrading human colonic mucin were examined in faecal specimens from healthy subjects and patients with inflammatory bowel disease. 2. The activity of sialidase was measured using a new physiological substrate related to mucus glycoproteins. In addition, acylneuraminate pyruvate lyase (N-acetylneuraminate lyase; EC 4.1.3.3.) and a novel O-acetylsialic acid esterase (sialate O-acetylesterase; EC 3.1.1.53) were detected. 3. The O acetylsialic acid esterase activity was readily detectable in partially purified fractions after Sephadex G-100 chromatography. 4. Patients with inflammatory bowel disease showed significant increases in acylneuraminate pyruvate-lyase and proteinase activity but sialidase activity did not differ from normal. The activity of these enzymes in neutrophils could not account for the differences observed. PMID- 3338254 TI - The strength, contractile properties and radiological density of skeletal muscle before and 1 year after gastroplasty. AB - 1. Skeletal muscle strength, contractile properties and radiological composition have been studied in seven morbidly obese adults (six female) before and 1 year after gastroplasty operations. The mean body weight fell from 138.3 kg (SD 25.2) to 99.7 kg (SD 23.0) (P less than 0.001). 2. The strength and contractile properties (force/frequency, relaxation rate and fatiguability) of both the adductor pollicis and quadriceps muscles were unaffected by the weight loss. 3. Computerized axial tomography scans obtained 1 year after surgery showed that the quadriceps contained an abnormally high proportion of fat. The mean fat content was 10.8% (range 3.0-30.1%) compared with 1.6% (range 0-5%) for normal muscle. Two individuals were scanned before and after surgery and the fat content of their quadriceps fell from 12.6% and 6.9% to 3.1% and 3.0%, respectively. 4. It is concluded that in obese individuals large amounts of weight can be lost, from both subcutaneous and intramuscular fat stores, without compromising either the strength or contractile properties of skeletal muscles. These results do not support the claim that skeletal muscle contractility is a sensitive indicator of changes in nutritional status. PMID- 3338255 TI - Muscle strength in the triceps surae and objectively measured customary walking activity in men and women over 65 years of age. AB - 1. Objective measurements of the maximal voluntary strength of triceps surae and the amount and speed of customary walking have been made in 56 men and 66 women aged over 65 years, who were living independently. 2. Strength was measured using a dynamometer based upon a hydraulic system (Bourdon tube). Walking was assessed, for amount using a mechanical accelerometer (pedometer) over a week, and for speed using a self-paced test for normal walking over 100 m on the level. The reliability and validity of these methods has been described. 3. The men were significantly stronger (1128 +/- 206 vs 873 +/- 177 N) even after adjustment for body weight; their amount of walking was similar to that of women, but they walked significantly faster (4.8 +/- 0.6 vs 4.2 +/- 0.6 km/h). Men were significantly more active in leisure pursuits (as assessed by questionnaire). 4. Significant associations between strength and chosen normal walking speed were found for both sexes (r = 0.41, P less than 0.001 for men and r = 0.36, P less than 0.01 for women). The amount of walking (daily stepscore as a mean from 7 consecutive days recorded) was significantly but less strongly correlated with strength (r = 0.30, P less than 0.05) in the men only. 5. Multiple regression analysis showed that in men neither age nor amount of walking had any further effect in addition to speed, but in women age had an additional effect (multiple R = 0.48). 6. An association has been demonstrated which raises the possibility of reversing loss of muscle strength through increased daily activity. PMID- 3338256 TI - A study of the structure of the gene for lecithin: cholesterol acyltransferase in four unrelated individuals with familial lecithin: cholesterol acyltransferase deficiency. AB - 1. We have used polyclonal antibodies and a complementary DNA clone for human lecithin:cholesterol acyltransferase (LCAT) to study LCAT protein and the structure of the LCAT gene, respectively, in patients with familial LCAT deficiency from Norway, Ireland, Germany and Italy. 2. The patients had low levels of non-functional LCAT protein in their serum as measured by rocket immunoelectrophoresis; its mol. wt. of approximately 68,000 was identical with that of LCAT in normal plasma, as judged by immunoblotting. 3. Enzymatic digestion of DNA samples from the patients produced LCAT gene fragments which were indistinguishable from those found in normal individuals. 4. We conclude that LCAT deficiency in these patients is not caused by a large deletion or rearrangement of the LCAT gene sequences. PMID- 3338257 TI - Nucleosides and bases in synovial fluid from patients with rheumatoid arthritis and osteoarthritis. AB - 1. Nucleosides and bases in physiological fluids result from metabolism of nucleic acids and nucleotides and from dietary sources. As nucleotide catabolism increases during tissue injury, nucleosides and bases could serve as useful biochemical markers in arthritis. 2. We have quantified nucleosides and bases in synovial fluid and plasma by high-performance liquid chromatography in order to examine whether nucleotide metabolism is increased in patients with rheumatoid arthritis and osteoarthritis. 3. At least ten u.v.-absorbing compounds were detected in plasma and synovial fluid; only urate, creatinine, hypoxanthine and uridine were present in identifiable and quantifiable amounts. 4. In synovial fluid from patients with rheumatoid arthritis the concentration of hypoxanthine was increased and that of urate decreased compared with osteoarthritis. 5. These data suggest that there is an increase in purine metabolism in the rheumatoid arthritis joint and that hypoxanthine is a potential marker of synovitis. PMID- 3338258 TI - Unaltered dopaminergic modulation of aldosterone secretion in cirrhosis. AB - 1. The responses of plasma aldosterone and plasma prolactin concentrations to metoclopramide (10 mg intravenously) were evaluated over 2 h in eight healthy controls and in 23 patients with cirrhosis (10 without and 13 with ascites). Plasma renin activity, glomerular filtration rate and renal sodium excretion were also determined. 2. Metoclopramide did not significantly influence plasma renin activity, whereas both plasma aldosterone and plasma prolactin rose significantly. The incremental areas under the curves did not differ among controls and cirrhotic patients without and with ascites. No significant correlations between plasma prolactin and aldosterone, either under basal conditions or after metoclopramide administration, were found in either controls or patients. 3. Glomerular filtration rate did not change after metoclopramide. Renal sodium excretion in controls and cirrhotic patients without ascites was also unaffected, whereas it decreased significantly in cirrhotic patients with ascites. In the latter, renal sodium excretion was inversely correlated with plasma aldosterone both under basal conditions and after metoclopramide administration. 4. The dopaminergic control of aldosterone secretion does not appear to be significantly altered in cirrhosis. Metoclopramide administration to cirrhotic patients with ascites leads to an increase in plasma aldosterone that may enhance renal sodium retention. PMID- 3338260 TI - Skeletal muscle glutamine production in thermally injured rats. AB - 1. The effect of thermal injury (33-35% of body surface area) on the regulation of glutamine metabolism was studied in skeletal muscles of rats 7 days after injury. 2. Injury increased the rates of glutamine production in muscle, skin and adipose tissue preparations, with muscle production accounting for over 90% of total glutamine produced by the hindlimb. 3. Injury produced decreases in the concentrations of skeletal muscle glutamine (36%, P less than 0.001), glutamate (39%, P less than 0.001), alanine (24%, P less than 0.001), pyruvate (35%, P less than 0.001), 2-oxoglutarate (51%, P less than 0.001) and adenosine 5' triphosphate (38%, P less than 0.001). The concentrations of ammonia (42%, P less than 0.001) and inosine 5'-phosphate (430%, P less than 0.001) were increased. 4. The maximal activity of glutamine synthetase was increased (22-40%, P less than 0.001) in muscles of injured rats, whereas that of glutaminase was unchanged. 5. Hindlimb blood flow decreased by approximately 15% in injured rats, which was accompanied by an enhanced net release of glutamine (80%, P less than 0.001) and alanine (44%, P less than 0.001). 6. It is concluded that there is an enhanced rate of release of both glutamine and alanine from skeletal muscle of thermally injured rats. This may be due to changes in efflux and/or increased intracellular formation of glutamine and alanine. PMID- 3338259 TI - Plasma [3H]noradrenaline kinetics in man: is separation of alumina extracts by high performance liquid chromatography necessary? AB - 1. After an 80 min intravenous infusion of 1-[3H]noradrenaline ([3H]NA) in 19 subjects, the proportion of alumina-extractable 3H due to [3H]NA was 86 +/- 2% in arterial and 78 +/- 2% in venous plasma. [3H]Dihydroxy-phenylethyleneglycol ([3H]DHPG) accounted for 8 +/- 1% in arterial and 13 +/- 1% in venous plasma. [3H]Dihydroxymandelic acid ([3H]DOMA) was not detected. 2. No time-dependent change in the proportion of alumina-extractable 3H due to [3H]NA was seen in either arterial or venous plasma over this period. In venous plasma the proportion of alumina-extractable 3H due to [3H]DHPG increased slightly between 30 and 80 min, from 10 +/- 1% to 13 +/- 1%. 3. The results were unchanged with chronic beta-blockade and with either 1-[2,5,6-3H]NA or 1-[7,8-3H]NA. 4. After [3H]NA infusion in man the radioactivity recovered after alumina extraction is predominantly [3H]NA and thus can be used directly to determine [3H]NA kinetics without the need for metabolite separation. PMID- 3338261 TI - Lithium clearance measurements as an indication of cyclosporin A nephrotoxicity in the rat. AB - 1. Measurements of the rate of lithium clearance, which provides an estimate of proximal renal tubular iso-osmotic reabsorption (i.e. sodium and H2O), were used to study H2O and electrolyte reabsorption during the development of cyclosporin A (CsA) induced nephrotoxicity. 2. CsA, administered daily by gavage at 50 mg/kg body weight, produced a nephrotoxicity which was characterized by reductions in the clearance rates of creatinine, sodium and potassium, and increased glycosuria, enzymuria and urine flow rate. 3. Decreased lithium clearance rate and increased proximal iso-osmotic reabsorption accompanied significant reductions in creatinine clearance rate. Absolute proximal tubular reabsorption, however, was not affected by CsA administration. 4. Reductions in the absolute distal tubular reabsorption of sodium, potassium and H2O were also observed. 5. Alterations in renal tubular function occur early in the development of CsA nephrotoxicity as a result of both direct proximal tubulotoxicity and an effect on the afferent arteriole. 6. Measurements of the rate of lithium clearance may be a useful adjunct to the diagnosis of CsA nephrotoxicity. PMID- 3338262 TI - Effect of inhaled methacholine on gas mixing efficiency. AB - 1. Pulmonary function tests, including alveolar mixing efficiency by the single breath and multi-breath methods, and ventilation scans were performed on 16 volunteer subjects. The tests were repeated after the inhalation of a methacholine aerosol in sufficient dosage to increase airways resistance. 2. After inhalation of methacholine there was a significant fall in mean series dead space of 31 ml (P less than 0.05), and mean multi-breath alveolar mixing efficiency fell from 68% to 36% (P less than 0.001), a fall occurring in all subjects. Mean single-breath alveolar mixing efficiency measured on the first breath of the nitrogen washout fell from 76% to 70%, but this change did not reach statistical significance (0.1 greater than P greater than 0.05). 3. In eight of the subjects, technically adequate lung scans and pulmonary function tests were obtained both before and not more than 30 min after methacholine inhalation. In seven there were obvious visible defects on the ventilation scans, and in five of these the computer-calculated underventilation score became abnormal. 4. Thus inhalation of methacholine causes maldistribution of ventilation, a fall in alveolar mixing efficiency and a fall in series dead space, presumably brought about by bronchoconstriction. The parallel component of this maldistribution of ventilation, as judged by 81mKr ventilation scanning, does not of itself seem to be sufficient to explain the fall in alveolar mixing efficiency, and therefore a degree of diffusion limitation is probably involved as well. PMID- 3338263 TI - Effect of changes in local skin temperature on postural vasoconstriction in man. AB - 1. The effects of locally induced alterations in skin temperature on the postural changes in skin blood flow of the foot were assessed in 38 healthy subjects in a constant-temperature environment (22 +/- 0.5 degrees C, mean +/- SD). 2. Moderate local cooling and warming of the foot (26-36 degrees C) was induced by blowing cold or hot air. Higher ranges of temperature (38-44 degrees C) were achieved by a thermostatically controlled disc heater. 3. Skin blood flow was measured before and during each change in local skin temperature using a laser Doppler flowmeter with the foot maintained at heart level, and placed passively 50 cm below the heart. Blood flow was measured in two skin areas: (i) the dorsum on the foot, where arteriovenous anastomoses are absent, and (ii) the pulp of the big toe, where these anastomoses are relatively numerous. 4. It was found that within the physiological temperature range of 26-36 degrees C the normal postural fall in foot skin blood flow was preserved, whereas it was markedly attenuated or totally abolished at higher temperatures (38-44 degrees C). The pattern of response was quite similar in areas having or lacking arteriovenous anastomoses. 5. It is suggested that the failure of postural vasoconstriction observed at the higher skin temperatures might contribute to some of the problems of cardiovascular adaptations seen in a hot environment. PMID- 3338265 TI - Haptic perception of objects in infancy. PMID- 3338264 TI - Naloxone increases mucosal fluid secretion in the inflamed and distended feline gall bladder: evidence for a possible protective mechanism by endogenous opioids. AB - 1. Endogenous opioid peptides are found in the enteric nervous system in the gastrointestinal tract. The opioid peptide enkephalin, which has anti-secretory action in the small intestine, is also contained in nerves in the gall-bladder wall. 2. In experimental cholecystitis, there is active fluid secretion by the epithelial cells into the gall-bladder lumen, when the intraluminal hydrostatic pressure is low. This fluid secretion to the lumen was abolished by intravenous administration of enkephalin, an effect that was blocked by naloxone pretreatment. The flux of fluid into the lumen was also abolished when the intraluminal hydrostatic pressure was raised to the level initially observed in the inflamed and obstructed gall bladder. Fluid absorption in the normal gall bladder was unaffected by enkephalin. 3. In experimental cholecystitis, naloxone, used as a non-specific antagonist of opiate action, did not affect the gall bladder mucosal fluid transport observed at a low intraluminal hydrostatic pressure, but it induced fluid secretion when this pressure was high. 4. It is suggested that a raised intraluminal hydrostatic pressure in experimental cholecystitis, which distends the gall bladder, releases endogenous opioids that inhibit active fluid secretion by the gall-bladder epithelial cells. This response may represent a defence mechanism that could be present also in the gastrointestinal tract. In the obstructed and inflamed gall bladder it may prevent progressive distension, ischaemia and perforation of the wall. PMID- 3338267 TI - Surface versus edge-based determinants of visual recognition. PMID- 3338266 TI - Acquisition of procedural knowledge about a pattern of stimuli that cannot be articulated. PMID- 3338268 TI - The development of induction within natural kind and artifact categories. PMID- 3338269 TI - C4-binding protein prevents spontaneous cleavage of C3 in sera of patients with hereditary angioedema. AB - We have studied the effects of polyclonal monospecific Fab' preparations against C1r, C1s, C1INH, C4, C4bp, and fragment Bb of factor B on complement activation in NHS and HAES. Furthermore, we have investigated complement activation in these sera after addition of purified C1s and purified C4bp. Blocking C1INH induced a spontaneous activation of the classical pathway in NHS and to a lesser extent in HAES. Addition of p-C1s resulted in a strong C3 conversion in NHS, but not in HAES. However, after the blocking of C4bp in HAES, addition of p-C1s produced a total C3 consumption. The ration of the protein concentration of C4bp to hemolytically active C4 was eight times higher in HAES than in NHS. This increased ratio may account for the resistance of HAES to the C1s induced C3 cleavage in our in vitro system and the stability of C3 in HAE despite C4 and C2 consumption in vivo. PMID- 3338270 TI - Effects of anti-C4 antibody on complement production by splenic and peritoneal macrophages. AB - We have previously shown that administration of anti-C4 antibody to cells in culture can suppress the synthesis and secretion of C4. Lymphoid cells must be present along with the C4 secreting macrophages to achieve suppression of full magnitude and long duration. In this publication we have demonstrated that treatment of peritoneal macrophages with intact anti-C4 antibody results in reduction of intracellular and secreted C4. Intracellular levels of pro-C4 rapidly returned to normal after removal of the suppressing antibody and extracellular levels of C4 secreted into the media returned to normal within 24 48 h. This is in marked contrast to our previously published results with splenic fragments where intracellular pro-C4 remained markedly reduced long after removal of anti-C4. Using pulse-chase experiments we now demonstrate that, after recovery from suppression, intracellular pro-C4 levels remain low in splenic macrophages because nascent C4 is processed through the cell more rapidly. This results in a smaller intracellular pool of C4, even in the face of normal or high levels of C4 synthesis in the postsuppression phase. Finally, we demonstrate that suppression of full magnitude and duration could only be achieved with intact anti-C4 antibody. F(ab')2 fragments were not capable of inducing complete suppression. PMID- 3338271 TI - Structure of C3f, a small peptide specifically released during inactivation of the third component of complement. AB - C3f, a peptide presumed to be generated by the combined actions of factors I and H on fluid-phase C3b, has been isolated and sequenced. The peptide is 17 residues long and has a molecular weight of 1,847 daltons. The amino-terminal sequence is, with the exception of a single residue, identical to that deduced for the 46 kilodalton polypeptide seen transiently in the generation of iC3b from C3b, and is in full agreement with the sequence deduced from cDNA analysis. In addition, high-pressure liquid chromatography of the digestion of C3b by factor I has shown that C3f is the sole peptide released during iC3b generation. PMID- 3338272 TI - Patients with CLL and hypocomplementaemia have an impaired serum bactericidal activity against the Salmonella minnesota Re mutant. AB - The bactericidal effect of 25 serum samples from 23 patients with chronic lymphocytic leukaemia (CLL) against the Salmonella minnesota S form and Re mutant has been studied. No killing of the S form was observed in any of the sera tested, whereas a normal bactericidal effect was found against the Re mutant (group 1) in 17/25 sera of CLL patients. By contrast, in 8 serum samples from 6 CLL patients no killing or a markedly delayed killing of the Re strain was observed (group 2). Significant differences in the complement levels were found between the sera of group 1 and group 2. In group 1 mostly normal or elevated complement levels were observed, while in group 2 levels of C4 and C2 were found to be strongly decreased. A significant correlation was found between the bactericidal effect on the one hand and the C4 and C2 levels on the other. PMID- 3338274 TI - Transmission of acquired immunodeficiency syndrome from patients to medical personnel. PMID- 3338273 TI - Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A2 levels with circulatory collapse. AB - Circulating phospholipase A2 (PLA2) has been recognized as a mediator of circulatory collapse in experimental endotoxic shock. To assess the role of serum PLA2 in septic shock in man, we determined serum PLA2 profiles in a prospective study in 12 patients with septic shock. During the hypotensive phase of sepsis, serum PLA2 levels were consistently elevated as high as 33,428 U/ml (normal range 115 +/- 12 [SE]; n = 101). In all 12 patients, PLA2 levels correlated directly with the magnitude and duration of circulatory collapse (p less than .001), with a progressive fall of serum PLA2 levels during convalescence. In contrast, serum PLA2 levels in patients with cardiogenic shock secondary to myocardial infarction remained low. In pancreatitis, PLA2 levels paralleled fluctuations of serum amylase and lipase, whereas in septic shock without pancreatic involvement, PLA2 changes were discordant with changes in pancreatic enzymes. As well, septic shock serum PLA2 failed to crossreact by radioimmunoassay with antiserum against human pancreatic PLA2. These data are consistent with an extrapancreatic source of intravascular PLA2 release during sepsis. Since endogenous serum PLA2 levels correlate directly with the magnitude of hypotension in both experimental endotoxic shock and clinical septic shock, and since parenteral administration of purified exogenous PLA2 reproduces hypotension in experimental models, we conclude that high levels of intravascular PLA2 may contribute similarly to the circulatory collapse in septic shock in man. PMID- 3338275 TI - Facilitation of difficult pulmonary artery catheterization. PMID- 3338276 TI - Improving the outcome and efficiency of intensive care: the impact of an intensivist. AB - Data from two 3-month time periods before and after the arrival of a pediatric intensivist were collected prospectively and compared to determine the intensivist's impact on ICU mortality, use of monitoring and therapeutic modalities, and efficiency of ICU bed utilization. Severity of illness and care modalities were determined daily for all patients with the Physiologic Stability Index and the Therapeutic Intervention Scoring System. The only major organizational change in the postintensivist period was the organization and implementation of a daytime ICU team. Case mix variables, including sex; medical/surgical, emergency/elective, and diagnostic distributions; and nursing hours/patient day, were equivalent in the pre-intensivist and postintensivist samples. After the intensivist's arrival, there was a significant decrease in admissions with very low severity of illness (Physiologic Stability Index less than 4; 52% vs. 34%; p less than .05) and a significant decrease in bed utilization by patients who received only monitoring services (27% vs. 17% of bed days; p less than .001). The severity of the illness-adjusted ICU mortality rate was significantly higher in the pre-intensivist period than in the postintensivist period (weighted mean mortality difference 5.3 +/- 2.6%; p less than .05). The incidence of both therapeutic and monitoring modalities increased in the postintensivist period. These results indicate that a pediatric intensivist can improve mortality rates and efficiency of bed utilization in the pediatric ICU. PMID- 3338277 TI - Energy metabolism of surgical patients in the early postoperative period: a reappraisal. AB - Energy metabolism was measured at the bedside in 22 uncomplicated surgical patients in the early (24 to 48 h) postoperative period with the use of continuous computerized indirect calorimetry with a canopy system. Energy production rates were higher than those predicted by the Harris-Benedict formula both in absolute value (1516 +/- 61 vs. 1387 +/- 49 kcal/day, p less than .05) and when normalized by body weight (BW; 23.5 +/- 0.5 vs. 21.7 +/- 0.5 kcal/day.kg BW, p less than .01) or by lean body mass (LBM; 32.8 +/- 0.8 vs. 30.2 +/- 0.9 kcal/day.kg LBM, p less than .01). Furthermore, surgical patients had higher energy production rates than those measured in 22 overnight fasted, resting healthy subjects matched for age, sex, and body size (23.5 +/- 0.5 vs. 21.8 +/- 0.6 kcal/day.kg BW, p less than .05). In both the patients and the control group, measured energy production bore a direct relation to LBM. We conclude that the early postoperative period of uncomplicated surgery is associated with a small (about 7%) but consistent increase in energy metabolism above the level observed in the overnight fasted, resting healthy individual. This increase appears to be an effect of surgery itself, and is not predicted by Harris-Benedict equations. PMID- 3338278 TI - Hemodynamic patterns of meningococcal shock in children. AB - Meningococcal shock still is associated with high mortality. Along with antibiotics and control of metabolic derangements, standard therapy involves monitoring and maintaining numerous cardiorespiratory variables. From 1980 to 1985, 39 children with meningococcal shock were treated in our pediatric ICU. We obtained full hemodynamic monitoring in 18 (12 survivors, six nonsurvivors). Two hemodynamic patterns were observed: hypovolemia and cardiac failure. Early death was generally related to refractory hypovolemia, probably secondary to severe capillary leak. Survival usually occurred when noticeable cardiac failure was controlled with early use of catecholamines and judicious fluid management. Because cardiac failure only slowly recovered, a therapeutic approach that aims not at normal variables but, rather, at survival variables seems appropriate. PMID- 3338279 TI - Effect of the calcium entry blocker verapamil on renal ischemia. AB - The ability of the calcium entry blocker verapamil to ameliorate the effects of renal ischemia was studied in ten sheep. Postanesthesia, bilateral cutaneous ureterostomies were placed in each sheep to facilitate urine collection and analysis. Both kidneys were made ischemic for one hour by occluding each renal artery. However, immediately before occlusion of the right renal artery, 0.05 mg/kg of verapamil was injected into the artery. Comparison of urinary creatinine excretion and urine volume for 72 h after reversal of ischemia demonstrated that those kidneys pretreated with verapamil had greater functional preservation (p less than .05). In this study, verapamil appeared to provide protection against renal damage after an ischemic insult. PMID- 3338280 TI - Decreased heart rate variability in significant cardiac events. AB - The heart rate variability (HRV) of 82 patients exhibiting sinus rhythm and admitted for possible myocardial infarction (MI) was evaluated. Using a simple information entropy measure to quantify the HRV, patients subsequently diagnosed with MI or experiencing significant dysrhythmia (n = 35) exhibited less entropy (0.28 +/- 0.15) within the first 24 h after admission than those patients (n = 45) with no MI (0.36 +/- 0.14; p less than .01). Although correlations between entropy and age and heart rate (HR) were significant (p less than .01), the additional explained variance was minimal. The groups were compared for sex, age, mean HR, past medical history and medications taken and were found to be statistically similar. In our patients without significant dysrhythmias on admission, HRV appeared to be an index for significant cardiac events, and thus may prove to be a useful tool in clinical situations where other objective decision criteria are lacking. PMID- 3338281 TI - Heparinization of samples for plasma ionized calcium measurement. AB - Maintenance of normal plasma ionized calcium concentration forms part of the management of the critically ill patient; it is, therefore, important to measure accurately plasma ionized calcium. We have compared the ionized calcium concentration of blood samples heparinized with a carefully measured amount of heparin with that of blood samples heparinized in the conventional fashion. The amount of heparin in the deadspace of a syringe was demonstrated to artifactually lower the plasma ionized calcium concentration. Samples for plasma ionized calcium measurement should be heparinized with a measured quantity of heparin, since the conventional technique introduces an unknown and probably excessive quantity of heparin into the syringe deadspace. PMID- 3338282 TI - Surgical intervention in acute pancreatitis. AB - There is no one operative treatment for acute pancreatitis. Surgery is indicated to resolve diagnostic uncertainty and perhaps to modify the early course of gallstone pancreatitis. Peritoneal lavage is useful in reversing early-phase systemic circulatory effects mediated by toxins in the ascitic fluid, but does not modify the underlying pancreatitis. When pancreatitis progresses to pancreatic and peripancreatic necrosis, the ultimate outcome is determined by a) the amount of necrosis, b) the extent of extrapancreatic necrosis, and c) bacterial contamination of necrosis. The amount of pancreatic regional necrosis that can be safely observed for healing is unknown; large collections tend to become infected secondarily and thus should be evacuated. Computed tomographic scanning is the best current means of detecting pancreatic necrosis and abscesses. Only percutaneous aspiration can reliably differentiate sterile from infected collections. As sepsis is the most common cause of death in acute pancreatitis, adequate surgical drainage is essential, while antibiotic therapy is only adjunctive. Aggressive treatment directed at the two principal causes of death, early-phase shock and late-phase sepsis, should reduce mortality to about 1% overall and to about 5% in cases complicated by regional necrosis and sepsis. PMID- 3338283 TI - Intravenous droperidol for the treatment of status asthmaticus. PMID- 3338284 TI - Postfebrile telogen effluvium in critically ill patients. PMID- 3338285 TI - TLC in combined restrictive and obstructive lung disease. PMID- 3338286 TI - New recommendations for standardizing spirometry. PMID- 3338287 TI - Rapid publication--A new service to authors. PMID- 3338288 TI - Endoscopic observation of peripheral airway lesions. AB - Peripheral airways of 2 mm or less in diameter were observed in 142 patients by means of an ultrathin bronchofiberscope measuring 1.8 mm in outside diameter. On the basis of the observed and photographed endoscopic findings, an endoscopic classification of peripheral airway lesions was proposed. The endoscopic findings showed changes in the bronchial wall consisting of reddening, pallor, absence of mucosal luster, edema, engorgement of blood vessels, irregular mucosal surface, and elevated mucosa. In the lumen, stenosis, obstruction, ectasis, and deformation due to pressure were recognized, in addition to excessive secretion and pigmentation as morphologic abnormalities or abnormal findings at bifurcation. PMID- 3338289 TI - Treatment of massive acute pulmonary embolism. The use of low doses of intrapulmonary arterial streptokinase combined with full doses of systemic heparin. AB - The efficacy of low-dose, locally administered streptokinase (SK) combined with full therapeutic systemic doses of heparin was investigated. Seven patients with angiographically proven massive acute pulmonary embolism were treated. Streptokinase, 10,000-20,000 units/hour, was administered directly into the left or right pulmonary artery for 9 to 24 hours. Heparin was administered concurrently. The number of unperfused segments of the infused lung shown on the lung scan decreased from 5 +/- 2 to 2 +/- 1 after 12-24 hours (p less than .01). No change was shown in the contralateral lung. The angiographic index of severity score in the infused lung decreased from 16 +/- 1 to 9 +/- 4 (p less than .01). The partial pressure of oxygen in arterial blood improved within four hours. In spite of the low doses of streptokinase, however, two major bleeding episodes occurred that required blood transfusion. In conclusion, low dose intrapulmonary streptokinase, combined with intravenous heparin, may provide a therapeutic option in patients with life-threatening massive acute pulmonary embolism in whom full dose lytic therapy may be hazardous, although even low dose lytic therapy was associated with risk. PMID- 3338290 TI - Lower prevalence of positive atopic skin tests in lung cancer patients. AB - Allergy prick skin testing was performed on 137 newly diagnosed patients with primary lung cancer and 137 age-(+/- 3 years) and sex-matched randomly selected control subjects. We also compared 38 patients with lung cancer and 38 of their closest in age, same-sex siblings. Demographic data, personal, medical, smoking and occupational histories were obtained by personal interview. We skin tested these individuals with a standard battery of seven common allergens and a diluent control. Fewer patients (35.8 percent) than control subjects (58.4 percent) responded with one or more positive skin reactions (p less than .005). There was no significant difference between patients (27.8 percent) and control subjects (37.2 percent) responding to more than one allergen. Fewer of the 38 sibling matched patients had one or more positive skin tests (23.7 percent) than did their siblings (55.3 percent) (p less than .01). There were fewer patients with greater than one positive skin test (15.8 percent) than sibling control subjects (42.1 percent) (p less than .025). There were no differences in smoking pack years between patients and siblings. Historic evidence of allergy was greater in both control groups compared to their matched cancer groups; p less than .05 for community controls, p less than .005 for sibling control subjects. These findings raise the possibility that atopy, by either immunologic or nonimmunologic means, protects against development of lung cancer, or alternately, that lung cancer affects immunologic status as gauged by (type 1) skin sensitivity. PMID- 3338291 TI - Tricuspid valve endocarditis due to Staphylococcus aureus. Correlation of two dimensional echocardiography with clinical outcome. AB - We studied 53 episodes (51 patients) of tricuspid valvular endocarditis caused by Staphylococcus aureus in a predominantly addicted population and correlated two dimensional echocardiographic findings with clinical outcome. Thirty-eight episodes with (vs 15 episodes without) tricuspid vegetations on the two dimensional echocardiogram were significantly associated with (1) longer duration of fever on therapy (mean of 12.3 days vs 6.8 days, respectively; p less than 0.005); and (2) higher frequency of increased right ventricular end-diastolic (RVED) dimension (25 of 38 cases [66 percent] vs two of 15 cases [13 percent], respectively; p less than 0.01). Only patients with increased RVED dimension (5/25; 20 percent) required tricuspid valvular surgery for prolonged fever or progressive right-sided heart failure (p less than 0.05 vs patients with normal RVED dimension). Tricuspid vegetations greater than 1.0 cm identified a subset of patients at increased risk for developing clinical right-sided heart failure during the active or convalescent phase of endocarditis (p less than 0.02 vs patients with tricuspid vegetations less than 1.0 cm). An unexpectedly high prevalence of asymptomatic prolapse of the mitral valve was observed in this population (23 of 53 episodes; 43 percent). Detection of tricuspid vegetations in patients with endocarditis due to S aureus is not a primary indication for early surgery, but identifies patients more likely to exhibit short-term and long-term complications of their infection. PMID- 3338292 TI - Amiodarone-induced pneumonitis. Assessment of risk factors and possible risk reduction. AB - Problems with pulmonary toxicity have emerged as a potentially limiting factor for amiodarone use. We prospectively studied 33 subjects treated with amiodarone for refractory arrhythmias. Serial clinical, radiographic and pulmonary function tests were correlated with the dose and duration of amiodarone treatment to define: a) prevalence of lung toxicity, b) subgroups of patients at particular risk for toxicity, c) potential interaction between amiodarone dose and toxicity. Considering all subjects, no significant change in lung volumes or airflow indices were noted; carbon monoxide diffusing capacity (DCO) underwent a mean reduction of 20.3 percent during treatment. Symptoms of possible pulmonary toxicity occurred in 27.3 percent of subjects. No type or degree of pretreatment cardiopulmonary dysfunction predicted lung toxicity. However, maintenance dose was correlated with toxicity; patients treated with doses of less than or equal to 400 mg per day from the start of treatment had insignificant reductions in DCO and did not develop symptoms. PMID- 3338293 TI - Endobronchial electrosurgery. AB - Endobronchial electrosurgery (EBES) with the aid of a fiberoptic bronchoscope and a diathermic snare has been performed in 14 patients with tracheal and bronchial tumors (eight with benign, one with carcinoid, and five with malignant tumors). Total eradication has been achieved in the nine patients with benign and carcinoid tumors. In some patients, EBES was supplemented with surgical removal with the biopsy forceps or laser coagulation. Electroexcision of the endobronchial portion of the tumor helped to clear the respiratory airways in three of the five patients with malignant tumors. Emergent EBES was performed in two patients with acute respiratory failure and massive hemorrhage caused by adenocystic and thyroid cancer of the trachea. PMID- 3338294 TI - Subjective effects of humidification of oxygen for delivery by nasal cannula. A prospective study. AB - Humification of oxygen prior to administration by nasal cannula is an expensive practice which has been justified on the basis that it improves the comfort of patients receiving supplemental oxygen therapy. Routine humidification of low flow oxygen (less than or equal to 4 L/min) delivered by nasal cannula has recently been challenged based on theoretic grounds and on the results of a clinical study. Nevertheless, we found, in a telephone survey of medium-sized American hospitals, that routine humidification of nasal cannula oxygen remains a common practice. To further evaluate the necessity of oxygen humidification, we prospectively evaluated, on a daily basis, the subjective complaints of consecutive patients in our institution who were ordered to receive nasal oxygen at relatively high flow rates (5 L/min). Of the 185 patients evaluated over a period of three wintertime months, 99 received humidified oxygen and 86 received dry oxygen. Complaints, especially dry nose and dry throat (42.9 percent and 43.9 percent of the daily interviews, respectively) were common in both groups, but the symptoms were relatively mild and did not increase significantly when oxygen was administered without prior humidification. We conclude that routine humidification of oxygen for administration by nasal cannula is not justifiable, and that cessation of this practice would result in significant reductions in both time and material costs in respiratory care. PMID- 3338295 TI - Total lung capacity. An insensitive measure of impairment in patients with asbestosis and chronic obstructive pulmonary disease? AB - The total lung capacity (TLC) is frequently used as a measure of respiratory impairment in patients with asbestosis. Because asbestosis and chronic obstructive pulmonary disease (COPD) exert opposite effects on the TLC, it may be an insensitive measure of impairment in patients with both abnormalities. To assess this, we compared asbestos-exposed patients with functional evidence of COPD and radiographic evidence of interstitial fibrosis (group 1) to those with interstitial fibrosis alone (group 2). Despite the two groups being comparable in degree of radiographic "fibrosis," no case of restrictive impairment (reduced TLC) was identified among those with both interstitial fibrosis and COPD (group 1), compared to 33 percent of those with interstitial fibrosis alone (group 2). In addition, those patients with both interstitial fibrosis and COPD, compared to those with interstitial fibrosis alone, were found to have greater impairment as measured by alveolar-arterial oxygen difference and diffusing capacity. We conclude that the TLC is an insensitive measure of impairment due to asbestosis in patients with the common setting of coexistent asbestosis and COPD. PMID- 3338297 TI - Poor breath sounds with good voice sounds. A sign of bronchial stenosis. AB - The auscultatory finding of disparity in breath and voice sounds, the former being absent or faint whereas the latter are easily heard when compared to the corresponding site over the opposite lung, predicts stenosis of a main, intermediate, or lobar bronchus. Stenosis limits airflow and consequently reduces turbulence, causing diminution or absence of breath sounds over the poorly ventilated region; however, flow-independent voice sounds are not significantly impaired. This sign was present in ten patients, in each of whom bronchial stenosis was confirmed by bronchoscopy. PMID- 3338296 TI - Diagnostic value of simultaneous determination of pleural adenosine deaminase and pleural lysozyme/serum lysozyme ratio in pleural effusions. AB - We have determined simultaneously the ADAp and Lp/Ls ratio in 138 pleural effusions: 61 tuberculous; 42 malignant; 14 transudates; five parapneumonic uncomplicated; six empyematous; and ten cases belonging to a miscellaneous group which included two disseminated lupus erythematosus; two posttraumatic; one pancreatitis; one pleuropericarditis by Mycoplasma; one viral pleuropericarditis; and three pulmonary embolisms. This has allowed us to clear the overlapping for the ADAp activity among tuberculous patients (two cases of lupus and three cases of malignant effusions) in our series. The overlap in the Lp/Ls ratio among tuberculous patients, two malignant, and two parapneumonic uncomplicated cases was also cleared. Fixing the ADAp values at 33 U and the Lp/Ls ratio at 1.2, the tuberculous pleural effusion cases were differentiated from the nontuberculous with a sensibility, positive predictive value, negative predictive value, and safety diagnosis of 100 percent. It has been proven that there is a good correlation between ADAp and Lp/Ls ratio (r = 0.717) and the ADAp and Lp (r = 0.660). PMID- 3338298 TI - Clinical role of bronchoscopy in adults with intrathoracic tuberculous lymphadenopathy. AB - Twenty-five adult tuberculosis patients with intrathoracic lymphadenopathy were studied. Intrathoracic tuberculous lymphadenopathy seems rare in Chinese and affects more older and female subjects. The most common symptoms were cough, followed by chills, fever and the most common physical finding was peripheral lymph node enlargement. The roentgenographic appearance of mediastinal lesions varied but often included right paratracheal involvement. Nine patients had clear lungs. Tuberculous involvement was limited to the lower lung field in seven out of 16 patients with concomitant parenchymal lesions. The remaining nine patients had pulmonary tuberculosis involving the upper lobes. Consolidation was the most common form of pulmonary lesion. A diagnosis was made on the basis of sputum examination in nine patients; however, peripheral lymph node examination yielded a higher diagnostic rate (90 percent). Endobronchial involvement was proved by bronchoscopy in 12 of 16 patients. In three instances, the final diagnosis could be documented after mediastinoscopy or exploratory thoracotomy. PMID- 3338299 TI - Nosocomial pneumonia. A multivariate analysis of risk and prognosis. AB - One hundred and twenty consecutive episodes of nosocomial pneumonia (NP) in 118 nonneutropenic adults admitted to a 1,000-bed teaching hospital were studied in order to investigate the prognosis and risk factors. The overall fatality rate was 36.6 percent. The identification of a "high-risk" microorganism (Pseudomonas aeruginosa, Enterobacteriaceae, and other Gram-negative bacilli, Streptococcus faecalis, Staphylococcus aureus, Candida sp, Aspergillus sp, and episodes of polymicrobial pneumonia), bilateral involvement on chest x-ray examination, the presence of respiratory failure, inappropriate antibiotic therapy, and age older than 60 years or an underlying condition ultimately or rapidly fatal were those factors selected by a stepforward logistic regression analysis as independently worsening the prognosis. A series of variables frequently quoted as predisposing to NP was determined to be either present or absent in the same 120 cases of NP and in an equal number of randomly selected control subjects. After adjusting for confounding, factors significantly predisposing to NP were tracheal intubation, depressed level of consciousness, underlying chronic lung disease, thoracic or upper abdominal surgery, prior episode of a large volume aspiration, and age older than 70 years. Since some of the factors influencing the risk or the prognosis of NP are amenable to medical intervention, a percentage of NP might be prevented and its prognosis can be improved. PMID- 3338301 TI - Sudden death in young soldiers. High incidence of syncope prior to death. AB - During the years 1974 to 1986, 44 young soldiers (mean age 21 +/- 3 years) died suddenly and unexpectedly in the Israel Defense Forces. Cardiac causes accounted for 54 percent of deaths; neurologic causes, 14 percent of deaths; other diseases, 9 percent; and in 23 percent, cause of death was unknown. Although most sudden deaths are considered unpredictable, preceding symptoms were reported in more than one half of the patients. We found that syncope had occurred in 23 percent of cases, chest pain in 11 percent, and febrile disease in 16 percent. Exercise-associated syncope occurred in 16 percent and exercise-associated death occurred in most (86 percent) of those cases. Diagnosis at the time of the preceding symptoms failed to predict the fatal diseases in most cases. Our report points out the high incidence of syncope prior death in young soldiers with sudden death. Although further prospective controlled studies are needed in order to confirm that impression, we suggest that the possibility of syncope followed by sudden death should be kept in mind while evaluating young patients presenting with exercise-associated syncope. PMID- 3338300 TI - The diagnosis and management of supraventricular tachycardia by transesophageal cardiac stimulation and recording. AB - Twenty-two consecutive patients underwent esophageal stimulation and recording for the diagnosis and management of supraventricular tachycardia. In 13 of these patients, the resting electrocardiogram was normal and in nine it showed pre excitation. Of the 13 patients with a normal resting electrocardiogram, supraventricular tachycardia was initiated in all. Seven patients had a ventricular-to-atrial interval greater than 70 ms during supraventricular tachycardia suggesting the presence of a concealed accessory pathway, and six patients had a ventricular-to-atrial interval less than 70 ms during supraventricular tachycardia suggesting reentry within the atrioventricular node. Supraventricular tachycardia was initiated in four of nine patients with pre excitation on the resting electrocardiogram and the accessory pathway was confirmed by a ventricular-to-atrial interval of greater than 70 ms during supraventricular tachycardia in these four patients. Atrial fibrillation was initiated in eight of the nine patients with pre-excitation on the resting electrocardiogram and the shortest R-R interval during atrial fibrillation was measured. The response to therapy was assessed in seven of these nine patients by further measurement of the shortest R-R interval during atrial fibrillation following treatment. Esophageal stimulation and recording provides a simple noninvasive procedure which can be utilized as a screening technique to identify patients with intranodal reentry and those with reentry utilizing an accessory pathway. Sequential assessment of the response to therapy, especially in those patients with pre-excitation, is of considerable value in treatment. PMID- 3338302 TI - Conduction system in a trained jogger with sudden death. AB - A 47-year-old extremely active, entirely asymptomatic trained jogger was found dead in bed. He was known to have had sinus bradycardia with first-degree atrioventricular block for eight years and a type 1 second-degree block five years prior to death. A permanent pacemaker had been inserted, and apparently the patient was then in good health and maintained his jogging program until he died suddenly. The conduction system revealed an atrioventricular node situated more to the left of the atrial septum than usual, which made tenuous connection with the surrounding atria due to marked fatty infiltration. The atrioventricular node as it joined the left-sided His bundle revealed fatty metamorphosis, fibrosis, disarray of myocardial fibers, and mononuclear cell infiltration. The right bundle branch was intramyocardial and fibrosed throughout. Increased aging changes of the left side of the septum with arteriolosclerosis and patchy fibrosis were present. This is the first case in which the atrioventricular node was more to the left side of the atrial septum with fatty separation of the node from the surrounding atrial musculature, with myocardial disarray of the nodal His bundle junction. Although congenital abnormality of the conduction system may remain silent without symptoms for a long time, it should be kept in mind that sudden death may occur sooner or later in some susceptible individuals. PMID- 3338303 TI - Phrenic nerve function in patients with diaphragmatic weakness and systemic lupus erythematosus. AB - Diaphragmatic weakness has been identified as one of the pulmonary manifestations of systemic lupus erythematosus. Whether this weakness results from a neuropathic or myopathic process has not been established. Thirty patients with SLE were screened for the presence of inspiratory muscle (IM) weakness. Detailed studies were performed in nine with IM weakness. All nine were found to have diaphragmatic weakness (mean +/- SD, maximal transdiaphragmatic pressure 50 +/- 12 cmH2O). Phrenic nerve latencies, evaluated using transcutaneous stimulation, were normal in all individuals excluding a demyelinating neuropathy. Compound diaphragm action potential (CDAP) with phrenic nerve stimulation was normal in six of these nine patients. Reduced CDAP in three of nine patients was consistent either with axonal degeneration of the phrenic nerve or diaphragm myopathy. Nerve conduction and electromyographic studies on peripheral nerves and muscles respectively failed to demonstrate an associated generalized neuropathy or myopathy. We conclude that diaphragmatic weakness in patients with SLE is both common and is very unlikely to be caused by a phrenic neuropathy. PMID- 3338305 TI - Spirometry and chest wall dimensions in achondroplasia. AB - Standard values for pulmonary function in short-limbed dwarfism are not available. Therefore, chest diameters and expiratory spirograms were measured in 58 female and 44 male subjects between 7 and 60 years of age with achondroplasia, the most common form of dwarfism. Standing height in adults was 49.6 +/- 3.2 (SD) inches with a sitting/standing height ratio of 0.66 (normal 0.52-0.53). Despite extremely short stature, only AP chest diameters in males were smaller than control subjects of similar age. The following equations were derived for forced vital capacity (FVC): males (under 25 years), FVC(L) = -3.56 + 0.162 X sitting height (in) + 0.067 X age (yrs); males (over 25 years), FVC(L) = -0.73 + 0.162 X sitting height (in) -0.047 X age (yrs); females (under 20 years), FVC(L) = -3.56 + 0.150 X sitting height (in) + 0.067 X age (yrs); females (over 20 years), FVC(L) = -1.92 + 0.150 X sitting height (in) -0.016 X age (years). Similar prediction equations were derived for FEV1 and FEF25-75%: FEV1/FVC % was 84.2 (+/ 6.5) for females and 88.0 (+/- 6.5) for males. We also compared the observed FVC measurements to values calculated using standing heights derived from the subject's sitting height, assuming a normal body proportion. The observed vital capacity in achondroplasia was only 67.6 (+/- 19.2) percent of that predicted for normally proportioned females and 72.4 (+/- 13.6) percent for males, suggesting reduced vital capacity in achondroplasia, due to reduced chest wall compliance or abnormal lung growth. PMID- 3338304 TI - Longitudinal pulmonary function changes in pigeon breeders. AB - We studied 15 subjects (14 men and one woman; seven symptomatic and eight asymptomatic) at three- to four-year intervals from 1967 through 1985 (18 years) to determine if continued pigeon antigen exposure in these groups was associated with a decline in pulmonary function greater than expected in healthy individuals. We collected immunologic studies at the initial visit, performed sequential pulmonary function studies and obtained chest radiographs. After compensating for the normal changes expected with increasing age, we found the declines in FVC, FEV1, and Dsb in the symptomatic group were nearly four times greater than expected. There was no significant difference in the decline of pulmonary function between asymptomatic subjects and the normal predicted declines with increasing age. We conclude that, if an individual has episodes of acute hypersensitivity pneumonitis, long-term exposure to pigeon antigens will result in an accelerated decline in pulmonary function. PMID- 3338306 TI - Aspiration of solid food particles into lungs of patients with gastroesophageal reflux and chronic bronchial disease. AB - The existence of a relationship between upper digestive tract impairment and respiratory disturbance is generally accepted. The aim of this study was to determine whether pulmonary aspiration, documented by labeled meal and lung scans, could be a contributory factor. Thirty-two patients with chronic respiratory complaints (19 men, 13 women, mean age: 57.8 yr), 29 of whom had an FEV1 below 80 percent of predicted values, and 13 healthy subjects (six men, seven women, mean age 50.9 yr) took part in a prospective study. Scintiscans showed gastroesophageal reflux (GER) in 27 patients (84 percent) and in five control subjects (38 percent). Lung contamination was ascertained in 24 patients (75 percent) and in two control subjects (15 percent) (p less than 0.001) 15 hours after a labeled solid meal. Vegetal fibers were found in sputum smears after mouth rinsing the day after ingestion of 8.5 g wheat bran in 72 percent of patients and in 77 percent of control subjects. Although two associated phenomena are not necessarily causally related, pulmonary aspiration documented by pulmonary scintigraphy did significantly correlate with gastroesophageal reflux, suggesting that aspiration resulting from reflux may perpetuate, if not initiate, chronic bronchial disease. PMID- 3338307 TI - Variability in theophylline volume of distribution and clearance in patients with acute respiratory failure requiring mechanical ventilation. AB - This study examines the intrasubject variability in theophylline volume of distribution (V) and clearance (CL) in critically ill, mechanically ventilated adults. Fifteen patients received two intravenous doses of theophylline approximately ten hours apart. Although there was no statistical difference between the mean VI (first dose, 0.51 L/kg) and V2 (second dose, 0.47 L/kg), the absolute difference between measurements of 0.15 L/kg was statistically significant (p less than .05). Range of differences follows: between VI and V2, 3.8 to 72.4 percent (mean, 33.5 percent); between CL1 and CL2, 6.1 to 100 percent (mean, 32.2 percent). Absolute difference between clearances was 0.019 L/kg/hr. A comparative error analysis revealed an absolute difference for V of 27.9 percent and for CL of 37 percent. Considerable intra-subject variability was shown for theophylline V and CL in these critically ill adults. Variability in V was not significantly different than variability in CL, and may result in severe underdosing or overdosing. PMID- 3338308 TI - Effect of pulmonary vascular pressure on lung lymph flow following seizures. AB - The effect of elevated baseline pulmonary vascular pressures on systemic and pulmonary vascular sequelae of prolonged seizures was studied in sheep. Five animals with seizures induced after baseline left atrial pressure elevations of 25 mm Hg were compared with animals treated with seizures alone. Seizure-induced elevations from baseline of systemic and pulmonary vascular pressures were identical in the two groups both in height and duration. In animals with left atrial balloon inflation prior to seizures, however, the peak pulmonary arterial and left atrial pressures were the sum of baseline elevation (induced by left atrial balloon inflation) and the seizure-induced pressure elevation. Accordingly, the resultant pulmonary vascular pressure and resultant pulmonary lymph flow elevations, were substantially greater in these animals with elevation in baseline pulmonary vascular pressures. Therefore, patients with pulmonary vascular hypertension are at greater risk for pulmonary edema during seizures. PMID- 3338310 TI - The bleeding disorder associated with open-heart surgery. PMID- 3338309 TI - Initial experience with a central respiratory monitoring unit as a cost-saving alternative to the intensive care unit for Medicare patients who require long term ventilator support. AB - The cost of delivering health care to Medicare patients in intensive care units (ICU), especially those on long-term ventilator support, has become a major financial burden to American hospitals. We established a central station, respiratory, noninvasive monitoring unit (NIMU) on a cardiac telemetry floor where nurse to patient ratio was 1:4 to 1:6 as a cost-effective alternative to the ICU which has a ratio of 1:2. During the first five months of operation, 55 patients were admitted to this unit, of which 11 were long-term ventilator Medicare patients. Seven of these 11 patients were successfully weaned and discharged from the hospital. Overall, a minimum of $21,724 was saved over five months by shifting these long-term ventilator patients from the ICU to the NIMU while quality of medical care remained or exceeded accepted standards. We conclude that alternative health care delivery systems such as the NIMU need to be investigated as safe, cost-reducing substitutes for selected ICU patients to prevent loss of quality medical care in the financial backlash of the present Medicare prospective payment schedule. PMID- 3338311 TI - A case of ring around the artery. Spontaneous pneumomediastinum. PMID- 3338312 TI - Pulmonary artery pressure and oxygen consumption measurement during supine bicycle exercise. PMID- 3338313 TI - Facial granulomas with nasal destruction. PMID- 3338314 TI - Tracheal blastomycosis. AB - A patient with pulmonary blastomycosis is presented. In addition, the patient had extensive involvement of the trachea. This is the first known reported case of tracheal blastomycosis. PMID- 3338315 TI - Amiodarone pulmonary toxicity presenting as a solitary lung mass. AB - Following treatment with amiodarone, a patient developed weight loss, fatigue and severe myopathy, without respiratory symptoms. A solitary lung infiltrate, impaired thyroid and liver function tests, and leukocytosis were evident. Biopsies from the lung lesion, liver, and bone marrow revealed foam cells. All these signs and symptoms subsided following cessation of amiodarone therapy. It is demonstrated that amiodarone may induce a localized lung lesion rather than diffuse pulmonary disease. PMID- 3338316 TI - Diffuse alveolar hemorrhage temporally related to cocaine smoking. AB - Previous reports of respiratory complications from cocaine abuse have focused on pulmonary barotrauma or a reduction in carbon monoxide diffusing capacity. We report a patient who developed life-threatening alveolar hemorrhage following repeated inhalation of alkaloid cocaine. PMID- 3338317 TI - An unusual complication of left ventricular pseudoaneurysm: hemoptysis. AB - Left ventricular aneurysm is a common sequela of anterior myocardial infarction. At the time of coronary artery bypass grafting, resection of this aneurysm is frequently undertaken to alleviate symptoms of heart failure and/or refractory ventricular tachycardia. Complications related to aneurysmectomy are uncommon. We describe an unusual patient who presented with hemoptysis related to the formation of a pseudoaneurysm which communicated with the lung parenchyma. The etiology of the pseudoaneurysm formation was an indolent, slow-growing infection. PMID- 3338318 TI - Transbronchial mediastinal cystography. AB - This article demonstrates a new method applied to two patients suffering from a subcarinal, mediastinal cyst, which, however, remained undetected by routine roentgenographic tests. In the first case, transbronchial needle aspiration was applied to remove the content of the cyst and injecting an x-ray contrast material (Endocistobil) for contrast roentgenography, whereas in the second patient the same x-ray contrast substance was injected by using an ultrathin catheter introduced through an opening which connected the cyst with the bronchial system. This method represents progress in the preoperative diagnosis of subcarinal mediastinal cysts. PMID- 3338319 TI - Diffuse contralateral pulmonary metastases in malignant mesothelioma. An unusual radiographic presentation. AB - We describe a patient with malignant pleural mesothelioma involving the lung parenchyma bilaterally in a diffuse nodular fashion. This pattern of metastasis is seldom reported for this tumor. PMID- 3338321 TI - Saccular aneurysm of the transverse thoracic aorta detected by transesophageal echocardiography. AB - A patient with a saccular aneurysm of the thoracic aortic arch presented with severe right ventricular failure due to pulmonary artery compression. Contradictory data were derived from computed tomography, pulmonary isotope perfusion scan and cardiac catheterization. Transesophageal echocardiography revealed a saccular aneurysm which compressed the main pulmonary artery and gave access to a fistulous connection to the left pulmonary artery. Surgery confirmed these findings. PMID- 3338320 TI - Encroachment upon the lungs of large chronic pericardial effusion. Pulmonary tamponade? AB - Pulmonary encroachment by a large chronic pericardial effusion is reported in a woman with pericardiocentesis whom we recently treated. A restrictive pulmonary impairment is documented with pulmonary function data obtained before and after drainage of the effusion and the patient's dyspnea improved. PMID- 3338322 TI - Endotracheal mass resulting from a transtracheal oxygen catheter. AB - A 50 percent or greater savings in oxygen usage and aesthetic benefits leading to increased compliance are reasons for increasing use of the transtracheal catheter for administration of home supplemental oxygen. Minor complications of the procedure are common and include catheter dislodgement, bronchospasm, subcutaneous emphysema, bleeding at the catheter site, as well as hemoptysis and wound infections. Rare complications include retroflexion of the catheter into the upper trachea from coughing, and fracture of the catheter with loss in the trachea. New, improved catheters and detailed descriptions for operator use may reduce the frequency of these complications. This report describes a potentially serious complication of a transtracheal catheter system which resulted despite appropriate use and care of the catheter. PMID- 3338323 TI - Systemic embolization from thrombus in normal left ventricles. AB - It is extremely rare for a thrombus to form in a normal functioning left ventricle. We present two patients in whom this occurred without any plausable explanation. In both instances the patients presented with systemic emboli and had no heart disease or hypercoagulable state. The diagnosis was made by two dimensional echocardiography and subsequently confirmed during surgery. PMID- 3338324 TI - Pneumothorax evacuation. PMID- 3338325 TI - Extrathoracic lymph node metastases in malignant pleural mesothelioma. PMID- 3338326 TI - Foreign body retrieval. PMID- 3338327 TI - Recognizing pulmonary torsion. PMID- 3338328 TI - Effect of phosphates? PMID- 3338329 TI - Ribavirin in desquamative interstitial pneumonia. PMID- 3338330 TI - Transtracheal oxygen to produce cough. PMID- 3338331 TI - Another unusual position for pulmonary artery catheter. PMID- 3338332 TI - Smoking cessation: role of nicotine dependence. PMID- 3338333 TI - Notes from a smoking cessation clinic. PMID- 3338334 TI - Why adoptees search: motives and more. AB - As both adoptee and psychiatrist, the author brings a double-barreled observation to the issue of search. PMID- 3338335 TI - Prevention of placement: critical factors in program success. AB - Initial studies of home-based family counseling programs have demonstrated success in keeping children out of institutional placements: little is known, however, about the characteristics of families or children or service utilization that might predict program success. This study of families where placement was avoided and families where a child ended up in placement throws light on the issue. PMID- 3338336 TI - Childhood depression: new theoretical formulations and implications for foster care services. AB - The current emphasis on permanency planning should not derail traditional concern about helping foster children to grow developmentally while in care. This concern coincides with the importance of enabling foster children, who frequently manifest symptoms of childhood depression, to overcome the learned helplessness that is so often a feature of depression. This kind of treatment may be called social care, and is inherent in daily living, as guided by trained foster parents and caretakers. PMID- 3338337 TI - The good touch/bad touch dilemma. AB - Child sexual abuse prevention programs of all kinds have multiplied. This paper examines one critical concept that is taught in virtually every program: the distinction between good and bad touch. Evaluation research has demonstrated that this is a difficult concept for young children to learn and retain. This paper offers the hypothesis that the reason for this difficulty can be found in the attribution skills of young children. PMID- 3338338 TI - Programming for preventing sexual abuse and abduction: what does it mean when it works? AB - Many kinds of educational programs and other approaches to teaching children about the dangers of sexual abuse and abduction by strangers can have the "side effect" of creating new anxieties in the children. The program described in this article is effective without introducing negative, anxiety-producing stories, examples, and other warnings. PMID- 3338340 TI - Retroperitoneal colopexy for adult rectal procidentia. A new procedure. AB - Nonresective fixation procedures are superior to resections in the management of rectal procidentia. A new operative procedure of retroperitoneal fixation of the redundant rectum and sigmoid after mobilization of the rectum up to the pelvic floor is described. The procedure was performed in 32 patients. In a follow-up ranging up to 11 years, only one recurrence of mucosal prolapse was seen. Rectal, bladder, and sexual functions were normal. There was a low wound infection rate and no mortality. The procedure appears superior to conventional operations for rectal procidentia and, at the same time, avoids usage of prosthetic materials for fixation with their known risk of complications. PMID- 3338339 TI - Intra-abdominal extrahepatic disease in patients with colorectal hepatic metastases. AB - The resection of hepatic metastases in patients with extrahepatic disease is of no proven benefit. Preoperative identification of extrahepatic disease may prevent unnecessary laparotomy. Preoperative evaluation including physical examination, computed tomography of the abdomen, full lung tomography or chest computed tomography, and radionuclide bone scanning identified extrahepatic metastases, most commonly in the lung, in 25 of 132 patients with purported isolated liver metastases. Of 107 patients with negative staging evaluations, intra-abdominal extrahepatic metastases were found in 26 percent (28 of 107) at laparotomy, most commonly in portal and celiac lymph nodes. The presence of extrahepatic disease correlated with greater than 25 percent hepatic replacement by tumor, presence of symptoms, and Dukes' C primary lesions; however, none was predictive. We were unable to develop a model to preoperatively predict the presence of intra-abdominal extrahepatic disease. The authors recommend a preoperative evaluation including physical examination, and computed tomographic scans of the abdomen and chest. A bone scan is required only in patients with symptoms referable to bone. Despite a negative preoperative evaluation, however, a considerable proportion of patients with colorectal hepatic metastases will have extrahepatic disease at the time of abdominal exploration. PMID- 3338341 TI - Constipation in the elderly. A physiologic study. AB - Colorectal motility was studied in 25 elderly patients with chronic constipation and compared with an asymptomatic control group (N = 17). Proctometrograms were performed to measure rectal volumes at sensory threshold and maximal tolerance, and rectal compliance. Anal sphincter pressures and reflexes were measured by conventional techniques. Indices of colonic motility were also assessed. Significant impairment of rectal sensory threshold was apparent in constipation. Six patients presenting with impaction demonstrated functional megarectums. The remaining 19 showed a significant reduction in maximal rectal volume and rectal compliance and 14 extruded the balloon. There were no differences in sphincter length or presence of the rectosphincteric reflex. Four patients had an absent pudendoanal reflex and the remainder significant prolongation. Total gastrointestinal transit times were prolonged in the constipation group, mainly distally due to rectal stasis. In two patients bisacodyl failed to elicit a sigmoid motor response. Constipation in the elderly is not merely due to delayed transit. Neurogenic deficits of sacral spinal cord function may be responsible for abnormalities in rectal motor and sensory function. PMID- 3338342 TI - Preoperative and postoperative evaluation by manometric study of the anal sphincter after coloanal anastomosis for carcinoma. AB - The purpose of the present study was to pre- and postoperatively evaluate the anal sphincter after coloanal anastomosis in 20 patients with carcinoma of the rectum at 5.5 to 8 cm from the anal verge. The 20 patients matched age and sex with the controlled subjects. Of the 20 patients, 17 with normal preoperative manometric studies when compared with control subjects underwent a coloanal anastomosis as described by Castrini, and three patients with preoperative incontinence underwent abdominoperineal resection. Manometric studies preoperatively, and postoperatively at three and 12 months, indicated a statistically significant decrease in squeezing pressure, and rectal compliance at three months that almost normalized by 12 months. The rectal compliance correlated with the number of bowel movements per day at three months (four to five per day) and at 12 months (two to three per day). The rectoanal reflex and length of pressure zone have remained unchanged. Results seem to indicate that anal continence can be preserved after coloanal anastomosis. PMID- 3338343 TI - The value of tissue mucin changes and CEA content in evaluation of benign colonic adenomas. AB - A combined histopathologic, histochemical, and immunohistochemical study of benign colorectal adenomas is presented. Specimens of 39 adenomas were studied by hematoxylin and eosin (HE) stain, alcian blue-periodic acid Schiff (AB-PAS), and high-iron-diamine-alcian blue (HID-AB). Carcinoembryonic antigen (CEA) was demonstrated by peroxidase-antiperoxidase (PAP) technique. Variable amounts of neutral mucin and decreased sulfated acid mucin content, as well as increased CEA content, were found in the dysplastic epithelium of benign colonic adenomas. These changes were not seen in normal colonic mucosa. It is suggested that the above-mentioned methods may represent an aid in the evaluation of malignant potential of benign polyps. PMID- 3338344 TI - The Hartmann procedure. Extended indications in severe intra-abdominal infection. AB - During a three-year period, 30 patients had emergency Hartmann procedures for diverticular disease (N = 12), carcinoma (N = 6), trauma (N = 3), and miscellaneous causes (N = 9). Two patients died postoperatively (6.7 percent) and wound infection developed in 60 percent of the patients. Planned relaparotomies for severe intra-abdominal infection were performed in ten patients (an average of 2.5 procedures per patient) with no mortality. In five cases a mucous fistula was converted into a Hartmann pouch; a preference for the Hartmann pouch in patients undergoing repeated explorations is discussed. Colorectal continuity was subsequently restored in 23 patients (76.6 percent). PMID- 3338345 TI - An implanted neuromuscular stimulator for fecal continence following previously implanted gracilis muscle. Report of a case. AB - A young woman had been treated previously with a gracilis muscle transposition because of anal atresia thus enabling her to maintain continence by active muscle contraction, which, however, she could sustain for only a few minutes. Implantation of a neuromuscular stimulator resulted in perfectly controllable sphincter function. PMID- 3338346 TI - Surgically removed adrenal metastasis from cancer of the rectum. Report of a case. AB - A woman was operated on for pulmonary metastasis four years after a radical resection of the rectum, and four years thereafter a solitary metastasis to the left adrenal was found. An elevated serum carcinoembryonic antigen (CEA) level indicated the lesion. Adrenalectomy was performed and the patient has been well with no further evidence of disease. PMID- 3338347 TI - New proximal L-shaped clamp for use in low anterior resection of the rectum. AB - The authors have designed a new proximal clamp for use in low anterior resection of the rectum. The new clamp enables the surgeon to section the rectum sharply at a right angle without fear of injuring the surrounding tissue. PMID- 3338348 TI - Patient-controlled analgesia vs. conventional intramuscular analgesia following colon surgery. AB - Though patient-controlled analgesia (PCA) has been in use for over a decade, it has been popularized only recently. Conventional techniques of intermittent intramuscular (IM) administration of analgesia have fallen short of meeting the needs of patients following major abdominal surgery. This has prompted a search for methods to improve postoperative pain management. Though PCA has been accepted in many hospitals, few studies comparing conventional IM administration of morphine with PCA have been performed. A prospective randomized study comparing IM- and PCA-administered morphine in 62 patients undergoing colon surgery was performed. A comparison of the efficacy of analgesia and extent of sedation using these approaches shows that PCA allows for analgesia with less sedation and less drug requirement than that of IM administration. No differences were noted in postoperative duration of ileus, duration of hospitalization, and total hospital costs. This study confirms the safety and efficacy of PCA, and should be considered the current optimal method of controlling pain following major colonic surgery. PMID- 3338349 TI - A simple technique for construction of a J-pouch. PMID- 3338350 TI - Anovaginal and rectovaginal fistulas in Crohn's disease. AB - Between 1957 and 1985, 886 women with Crohn's disease and an intact distal large bowel were seen at St. Mark's Hospital. Ninety of these patients developed a fistula between the vagina and anus or rectum at an average age of 34 years. The track of the fistula was clearly documented in 80 patients and was extrasphincteric or suprasphincteric in 36, transsphincteric in 42 (high 13, low 29), and superficial in two. Of the 90 patients, 12 (13 percent) were managed throughout without recourse to surgery. Twelve (13 percent) had the fistula laid open or drainage of an abscess as the only surgery. Twelve (13 percent) underwent repair of the fistula and, of these, eight remain symptomatically cured. One has had further symptoms but no surgery while three later underwent proctectomy for rectal disease. In eight patients the colon was removed and the rectum defunctioned and in 34 the rectum was excised as the initial surgery after development of the fistula. The remaining 12 (13 percent) underwent later proctectomy for rectal disease or failed conservative management of the fistula. Extensive colonic involvement, rectal disease, or associated anal lesions were the main reasons for rectal excision in 38 patients. In only ten was the rectovaginal fistula a prominent indication for proctectomy. As medical treatment, repair, or other local surgery were successful in one third of the patients, these options should always be considered in the first instance. PMID- 3338351 TI - Gastric emptying of mixed solid-liquid meal in patients with intestinal pseudoobstruction. AB - Gastric emptying of solids and liquids was evaluated simultaneously in 11 patients with intestinal pseudoobstruction. Despite a normal upper gastrointestinal series in most patients, over two thirds of the patients had abnormal gastric emptying of solids and/or liquids. Half these patients exhibited delayed emptying of solids and accelerated emptying of liquids. Alterations in motility patterns were observed in the four patients tested including decreased frequency or absence of migrating motor complexes originating in the stomach, shortening or absence of phase I, and loss of distinct fasted and fed patterns. Both basal values and mean postprandial increments in serum gastrin concentrations were lower in the patients, whereas no significant difference was found for pancreatic polypeptide concentrations when compared to normals. Our findings emphasize the functional heterogeneity of patients with intestinal pseudoobstruction. In addition, in contrast to previous reports which used barium meals to access gastric function, we observed a high prevalence of gastric emptying disturbances in these patients, suggesting that the motility disturbance is not restricted to the small intestine. PMID- 3338352 TI - Charcoal bezoar. Small-bowel obstruction secondary to amitriptyline overdose therapy. AB - Nasogastric administration of activated charcoal is effective in decreasing the half-life of amitriptyline. A case is reported in which this therapy for amitriptyline overdose led to charcoal bezoar formation and small-bowel obstruction. Amitriptyline's atropinic side effects on the gut make this a possible complication in such patients. PMID- 3338353 TI - Ethanol and L-amino acids. PMID- 3338355 TI - Digestive Diseases and Sciences: Its new editors and their policy. PMID- 3338354 TI - Effect of cholecystectomy on mouth-to-cecum transit of a liquid meal. AB - Mouth-to-cecum transit and serum bile acid profile after ingestion of a lactulose labeled liquid meal (440 kcal) were measured in eight patients with gallstones and a radiologically functioning gallbladder before and three to five months after cholecystectomy and in 15 controls. In the patients mouth-to-cecum transit was longer after the operation, 87.5 +/- 18.5 (mean +/- SEM) min vs 57.5 +/- 9.7 min (P less than 0.05). Mouth-to-cecum transit times before and after the operation were not different from controls (58.0 +/- 6.7 min). Serum bile acid AUCs were similar (P = NS) in patients and controls, while total bile acid and cholylglycine fasting concentrations were higher after cholecystectomy (P less than 0.05 and P less than 0.01 respectively). Cholecystectomy prolongs mouth-to cecum transit of a liquid meal. PMID- 3338356 TI - Effect of cigarette smoking on extent of acid-secreting area and intestinal metaplasia in the stomach. AB - The association of cigarette smoking and other variables with the extent of the acid-secreting area and intestinal metaplasia were investigated by multivariate analysis. Studies were made by the endoscopic Congo red-methylene blue test developed in our hospital. In this test, acid-secreting areas and areas of intestinal metaplasia could be identified as discolored areas and areas staining blue with methylene blue, respectively. In multivariate analysis, the following variables were associated with a reduction in the size of the acid-secreting area in decreasing order of importance: the smoking index and age. The following factors had little or no influence on the size of the acid-secreting area: sex, and the consumption of aspirin and nonsteroidal, nonsalicylate, antiinflammatory drugs (NSNSAIDs). In general, in patients with a high smoking index, the acid secreting area was small. Smoking had an influence in both younger and older patients and had more influence in females than in males. Multivariate analysis also shows that the following factors were associated with an increase in the area of intestinal metaplasia in decreasing order of importance: the extent of the acid-secreting area, age, and the smoking index. The following factors had little or no influence on the area of intestinal metaplasia: the consumption of aspirin and NSNSAIDs and sex. In general, in patients with little or no acid secreting area, the area of intestinal metaplasia was extensive. These findings indicate that smoking is associated with reduction in the size of the acid secreting area and so in development of intestinal metaplasia. PMID- 3338358 TI - Milk feeding and xylazine treatment induce increased antroduodenal motility in young cattle with opposite effects on duodenal digesta flow rate. AB - Antroduodenal myoelectrical activity and duodenal digesta flow rate in young cattle were assessed by implanted nichrome wire electrodes and reentrant duodenal cannulation with interposed flow-meter. In addition, a small glass electrode was inserted through a duodenal cannula to continuously measure the pH of duodenal contents. When eating only hay ad libitum, the duodenal myoelectrical activity showed the usual migrating myoelectrical complex (MMC) pattern. Duodenal contents pH rose sharply at the end of a period of repetitive spike activity (RSA), or phase III, from pH less than 2 to greater than 5 and remained high through most of the subsequent period of no spike activity (NSA), or phase I, during which there was no antral spiking and no flow of duodenal contents. Feeding milk (pH 6.5) caused a marked increase in antroduodenal spike activity and intraduodenal flow rate, with a concomitant rapid rise in duodenal contents pH from 1.8 +/- 0.3 (SEM) to 5.0 +/- 0.2 which then slowly declined over the next few hours. Within 5 min after the administration of the alpha 2-adrenergic agonist xylazine (25 and 50 micrograms/kg intramuscular), there was a significant increase (P less than 0.05) in antroduodenal spike frequency and a concomitant marked drop in intraduodenal flow rate with a sustained low pH of intraduodenal contents. The results suggest that: (1) continuous measurement of proximal duodenal pH adds a useful dimension to documenting relationships between antroduodenal myoelectrical activity and duodenal digesta flow rate; and (2) increased spike activity in the antroduodenal region does not necessarily indicate an increased duodenal flow rate is occurring. PMID- 3338357 TI - Anorectal functioning in fecal incontinence. AB - Manometric testing was performed on three groups of subjects: 14 patients complaining of fecal incontinence, 14 age- and sex-matched continent patients, and 14 sex-matched younger normal controls. The younger group displayed significantly stronger contractions of the external anal sphincter and puborectalis than the two patient groups, which did not differ. No differences were found in the relaxation of the internal and sphincter. The incontinent group required a significantly larger stimulus in order to detect rectal distension compared to either the continent patients or the younger normals. An additional group of unmatched normals and incontinent patients demonstrated significant differences in their ability to retain rectally infused saline. The patients leaked sooner and retained less; however, the performance of the normals was considerably reduced from that reported in previous studies. The aging process seems to result in weakening of the striated muscles of the anal canal, although fecal incontinence need not occur. The afferent limb of the anorectal sensorimotor mechanism does not necessarily deteriorate with aging. A lower threshold for sensation of rectal distension among continent individuals apparently helps them to avoid incontinent episodes, even though maximum contractile pressures in their anal canal are no different from a comparable group of incontinent individuals. PMID- 3338360 TI - Light and electron microscopic and autoradiographic studies on N-methyl-N amylnitrosamine-induced rat esophageal carcinogenesis. AB - The purpose of this study was to investigate the histogenesis of experimental tumors in the rat esophagus. Thirty rats received 0.0015% N-methyl-N amylnitrosamine (MNAN) in the drinking water for 12 weeks. Another 30 rats received tap water. All rats then received tap water until sacrifice. Rats from each group were sacrificed immediately after MNAN administration, four weeks after, and eight weeks after. One hour before sacrifice, [3H]TdR was injected by tail vein to label proliferating cells. The entire esophagus and stomach were removed and processed for light and electron microscopy and autoradiography. The overall frequency of esophageal tumors after MNAN was 83% and did not differ significantly among the three experimental groups. Tumors were primarily papillomas and squamous cell carcinomas and occurred with equal frequency in the upper, middle, and lower thirds of the esophagus. No tumors were found in the squamous-lined forestomach. Electron microscopy revealed abundant tonofilaments, free ribosomes, and mitochondria accompanied by vacuoles. By autoradiography, esophageal epithelial proliferation was markedly stimulated in nontumorous mucosa from all three experimental groups. We conclude that MNAN ingestion for 12 weeks reliably produces papillomas and squamous cell carcinomas throughout the rat esophagus, but not in the squamous-lined forestomach, and that MNAN stimulated marked epithelial proliferation which is accompanied by thickening of the epithelium in nontumorous esophageal mucosa. PMID- 3338359 TI - Intestinal absorption of bile acids in the pig. Role of distal bowel. AB - The role of distal bowel in intestinal recycling of total bile acids was investigated in five healthy, conscious, normally fed pigs. Total bile acids appearing in the portal blood of fistulated animals were measured when bile irrigated the whole bowel (control period) and again when it was diverted at 1 m proximal to the ileocecal valve so that enterohepatic circulation was limited to only the last meter of ileum plus large bowel. Measurements were taken just after the bile had been diverted and then four days later when a new steady state was reached. Under steady-state conditions bile acid reabsorption rate in distal bowel was 20% of the normal rate. This result has been discussed taking into account the high but transient ability of distal bowel to spare bile acids measured in the first hours after bile diversion. The present experiment, together with some other in vivo trials on small laboratory animals, indicate that the proximal bowel may take a large part in bile acid absorption and that we need to reevaluate the notion that bile acid absorption takes place mainly in distal bowel. PMID- 3338361 TI - Discrepancies between gastric mucosal and urinary pepsinogen A patterns and in vitro synthesis and secretion of human pepsinogen. AB - The relationship between electrophoretic pepsinogen A (PGA) patterns from urine and gastric mucosa was studied in healthy volunteers and in patients with various gastric disorders. Discrepancies between urinary and gastric PGA patterns were found in 63.3% of the individuals. In 9% of the subjects with these discrepancies, the phenotype class in urine was different from that in gastric mucosa. The differences were found in all diagnostic groups. The highest frequency of differences was found in patients with gastric ulcer. The differences were not related to the serum PGA level. More than 80% of the differences were caused by a lower relative intensity of pepsinogen A fraction 5 (Pg5) in urine than in gastric mucosa. The possible origin of differences in PGA isozymogen patterns was studied by organ culture of gastric biopsies. In vitro synthesis and secretion of pepsinogens were studied by electrophoresis and autoradiography. The synthesis rate of PGA in biopsies of 1-2 mm diameter was 40 100 ng/hr. Posttranslational modification of PGA isozymogens was demonstrated. Pg2 and part of Pg4 probably are secondary products of Pg3 and Pg5, respectively. In some individuals the secretion rate of Pg3 was low compared to the other isozymogens. The conversion of Pg3 into Pg2 and the differential secretion of the isozymogens may explain some of the discrepancies between gastric and urinary PGA patterns. PMID- 3338362 TI - Effect of placebo on meal-stimulated gastric acid secretion and serum gastrin concentration. Studies in healthy volunteers and duodenal ulcer patients. AB - The effect of placebos on gastric acid secretion in humans is unknown, even though placebo therapy is relatively effective in ulcer patients. Therefore, we evaluated the effect of a placebo capsule on meal-stimulated gastric acid secretion and serum gastrin concentrations in 10 healthy subjects and also in 10 patients with chronic duodenal ulcer. Each subject and patient was studied twice and in random order, once with placebo therapy prior to the meal and once without placebo. In either healthy subjects or duodenal ulcer patients, meal-stimulated acid secretion and serum gastrin concentrations were not significantly different with or without placebo administration. These studies demonstrate that a placebo capsule, administered by a physician just prior to a meal, has little, if any, effect on acid secretion or gastrin release in response to the meal. Any beneficial effects of placebos in treating patients with peptic ulcer disease are probably unrelated to inhibition of meal-stimulated gastric acid secretion. PMID- 3338364 TI - Does healing of esophagitis improve esophageal motor function? AB - This study investigates whether healing of erosive esophagitis leads to an improvement of esophageal motor abnormalities. Manometric studies were performed in 18 patients with erosive esophagitis before and after healing of the mucosal lesions and in 15 healthy controls. Nine patients were treated with a Nissen fundoplication and nine with H2-receptor antagonists. After healing, patients were followed for a mean duration of 3.0 +/- 0.4 years. Compared to controls, patients had significantly lower contraction amplitudes and lower esophageal sphincter pressures (P less than 0.01), while the duration and velocity of esophageal contractions was similar in both groups. Lower esophageal sphincter pressure increased after surgical treatment, while no such changes were observed in medically treated patients. In both groups amplitude, duration, and velocity of esophageal contractions were not affected by healing of esophagitis. On extended follow-up, all surgically treated patients remained asymptomatic while eight of nine medically treated patients developed a symptomatic relapse which was accompanied by erosive esophagitis in six of them. The lack of improvement in esophageal motor function after healing of esophagitis may contribute to the frequent occurrence of relapse in medically treated patients. PMID- 3338363 TI - Effects of upper dorsal sympathectomy on esophageal motility in humans. AB - To evaluate the role of the sympathetic nervous system in modulating esophageal motility, esophageal manometry was performed on two groups of patients who underwent upper dorsal sympathectomy for relief of palmar hyperhydrosis. In six patients sympathectomy was done by the supraclavicular approach, with removal of T2 and T3 ganglia. Manometry was performed before the operation and three weeks after it. In seven other patients sympathectomy was done by the axillary approach, with removal of T2-T4 ganglia. Manometry in this group was performed 28.4 +/- 22.4 months after the operation. Fifteen individuals with an intact sympathetic system served as controls. Manometric parameters evaluated were esophageal contraction amplitude and duration and lower esophageal sphincter pressure. The difference between the results obtained in the pre- and postoperative periods in the first group was not statistically significant. The differences between the two patient groups and between the patient groups and the control group were not statistically significant either. We conclude that upper dorsal sympathectomy does not affect esophageal motility in man. PMID- 3338365 TI - 24-hour esophageal pH monitoring before and after medical therapy for reflux esophagitis. AB - Medical treatment of gastroesophageal reflux disease often results in improvement of symptoms. The purpose of this study was to determine if improvement in symptoms and endoscopic appearance after treatment was associated with a reduction in reflux, as measured with 24-hr pH recordings. Twenty patients with severe chronic reflux esophagitis participated in an eight-week double-blind trial of medical therapy with metoclopramide and cimetidine versus placebo and cimetidine. Significant symptom score improvement was noted in 11 patients. Eleven patients also had improvement in the endoscopic appearance of the esophageal mucosa, and eight of these patients had significant symptom improvement. Initial 24-hr pH recordings were abnormal in all patients, evidenced by an esophageal pH less than 4 during 20% of the study period. Improvement in 24 hr results was noted in only five patients--three with clinical and endoscopic improvement, and two with no improvement. In conclusion, there was no relationship between clinical improvement and the results of 24-hr pH recordings. Successful symptom relief and endoscopic healing of esophagitis during medical treatment may occur despite persistent reflux of gastric contents. PMID- 3338367 TI - Improvement of oral colonic lavage with supplemental simethicone. AB - We have noted that colons of patients prepared for colonoscopy with Golytely, a nonabsorbable electrolyte lavage solution, frequently contain foam which may obscure small mucosal lesions. Therefore, a randomized, blinded controlled trial was performed to determine the prevalence of Golytely-induced foam and the effect of supplemental simethicone in decreasing the prevalence of foam. Foam was present in 32% of colons prepared with Golytely alone but in none of the colons prepared with Golytely supplemented with simethicone. In addition, only 5% of colons prepared with supplemental simethicone had residual stool noted at the time of colonoscopy, a significant improvement over the 39% prevalence of residual stool in colons prepared with Golytely alone. Addition of simethicone to Golytely lavage decreases the prevalence of colonic foam and residual stool. PMID- 3338366 TI - Lactoferrin secretion in alcoholic pancreatic disease. AB - Lactoferrin, a nonenzyme protein normally secreted in small amounts in pancreatic juice, has been reported by several investigators to be secreted in large amounts in chronic pancreatitis. Whether this increased secretion first occurs at an early or late stage of alcoholic pancreatic disease is unknown. In this study we measured lactoferrin and enzyme outputs in duodenal juice from 10 healthy subjects and three groups of alcoholic subjects: asymptomatic chronic alcoholics without evidence, clinically or biochemically, of pancreatitis (10), those recovered from acute pancreatitis (8), and those with established chronic pancreatitis (8). A multilumen, marker-perfused duodenal catheter was used to aspirate basal pancreatic secretions at the ligament of Treitz. The mean ( +/-SE) lactoferrin concentration in duodenal juice for the four groups of subjects was: healthy, 0.7 +/- 0.1 micrograms/ml; asymptomatic alcoholics, 5.5 +/- 1.5 micrograms/ml; alcoholics who had recovered from acute pancreatitis, 7.4 +/- 0.8 micrograms/ml; and alcoholics with chronic pancreatitis 7.1 +/- 1.9 micrograms/ml. The three groups of alcoholics each had a greater lactoferrin concentration than the normals (P less than 0.005). The output of lactoferrin in the four groups paralleled the concentration in that the three groups of alcoholics had a significantly greater output: healthy subjects, 3.4 +/- 0.5 micrograms/kg/hr; asymptomatic alcoholics, 25.7 +/- 7.4 micrograms/kg/hr; alcoholics recovered from acute pancreatitis, 80.1 +/- 27 micrograms/kg/hr; and alcoholics with chronic pancreatitis, 90.9 +/- 32 micrograms/kg/hr. The output of chymotrypsin and trypsin in the four groups of subjects revealed increased secretory rates in the asymptomatic alcoholics and the alcoholics recovered from acute pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338368 TI - Gastric motility is an important factor in the pathogenesis of indomethacin induced gastric mucosal lesions in rats. AB - Effects of atropine, cimetidine, and 16,16-dimethyl prostaglandin E2 (16,16 dmPGE2) on indomethacin-induced gastric lesions were investigated in rats by correlating their effects on gastric acid and HCO3- secretion and motility. Subcutaneously administered indomethacin (25 mg/kg) produced gastric mucosal lesions within 4 hr. In parallel studies, an equivalent dose of indomethacin inhibited gastric HCO3- secretion, and stimulated gastric motor activity measured as intraluminal pressure recordings, whereas acid secretion was unaffected. The lesions induced by indomethacin were significantly prevented by three agents: cimetidine (100 mg/kg), which reduced acid secretion; atropine (1 mg/kg), which reduced acid secretion and gastric motility; and 16,16-dmPGE2 (10 micrograms/kg), which reduced acid secretion and motility and increased gastric HCO3- secretion. If acid (150 mM HCl) was infused into the stomach (1.2 ml/hr) during indomethacin treatment, only the latter two agents significantly prevented the formation of gastric lesions in response to indomethacin. Since only the effect on gastric motility was common to these two agents (atropine and 16,16-dmPGE2), the increased gastric motility may be an important pathogenetic factor in indomethacin-induced gastric lesions. The presence of acid as well as a deficiency of endogenous PGs may be prerequisite for later extension of the lesions but cannot account for the induction of mucosal lesions in rats following administration of indomethacin. PMID- 3338369 TI - Acid-induced esophagitis in cats is prevented by sucralfate but not synthetic prostaglandin E. AB - The cytoprotective effects of liquid sucralfate and a synthetic analog of prostaglandin E1 (PGE1) on acid-induced esophagitis in cats were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N HCl at 1 ml/min for 20 min. Animals were infused for either one or three days. Mucosal lesions were evaluated by blinded investigators using both fiberoptic endoscopy and light microscopy. Histologic changes included basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions in both one- and three-day infusions, demonstrated by both endoscopy and quantitative histologic scoring. Indomethacin (200 micrograms/kg) given prior to sucralfate and acid did not affect sucralfate cytoprotection. Synthetic PGE1, given in doses of 5 micrograms/kg and 100 micrograms/kg, afforded no esophageal cytoprotection. These studies indicate that sucralfate is cytoprotective against acid-induced esophageal injury in cats, an effect that does not appear to be mediated by prostaglandin. In addition, synthetic PGE1 does not confer protection in this animal model. PMID- 3338370 TI - Gastrointestinal damage induced by platelet-activating factor. Inhibition by the corticoid, dexamethasone. AB - Intravenous infusion of platelet-activating factor (PAF-acether) induces extensive vasocongestion and damage in the stomach and small intestine of the rat. The effect of pretreatment with the corticoid dexamethasone (2 mg/kg) on such gastrointestinal damage in the rat has now been investigated, using macroscopic observation and the release of acid phosphatase, as an enzyme marker of cell disruption. Administration of PAF-acether (100 ng/kg/min intravenously, for 10 min) induced focal, intense hyperemia and hemorrhage in all the regions of the gastrointestinal tract, with the exception of the distal colon. This damage was associated with an increase in the release of acid phosphatase into the lumen of the stomach, duodenum, jejunum, and ileum following incubation in vitro. Pretreatment with dexamethasone reduced the macroscopically apparent gastrointestinal damage following PAF-acether administration and abolished the intraluminal release of acid phosphatase. Dexamethasone also significantly suppressed the hemoconcentration, as determined by changes in platelet and erythrocyte count and hematocrit, 30 min after PAF-acether infusion. Thus, as in endotoxin shock, this glucocorticoid can reduce the gastrointestinal damage associated with PAF-acether administration. PMID- 3338371 TI - Hypereosinophilic syndrome. Association with chronic active hepatitis. PMID- 3338372 TI - Prolonged jaundice following ketoconazole-induced hepatic injury. AB - Two patients developed prolonged and progressive jaundice associated with ketoconazole-induced hepatic injury although the drug was discontinued before or shortly after the onset of symptoms of hepatic toxicity. One patient, who had been jaundiced for eight weeks and was not improving, showed prompt clinical improvement and progressive resolution of jaundice following therapy with prednisolone. Liver biopsy before therapy showed marked cholestasis in all acinar zones and moderately severe fibrosis in the space of Disse. The other patient, who was less severely jaundiced, showed spontaneous resolution although he remained jaundiced for 11 weeks. Liver biopsy performed three weeks after onset of symptoms showed a moderate degree of cholestasis in acinar zone 3 and collagen deposition about the terminal hepatic venules and within the space of Disse. These cases are reported because of the unique clinical course, documentation of the morphologic features, and experience with corticosteroid therapy. PMID- 3338374 TI - Mycobacteria, infant goats, and Crohn's disease. PMID- 3338373 TI - Metastatic choriocarcinoma to the stomach presenting as hematemesis. PMID- 3338375 TI - Sensitivity and specificity of elastase. PMID- 3338376 TI - A piece of my mind. PMID- 3338377 TI - Does pan-pancreatic involvement occur in IDDM? PMID- 3338378 TI - Chronic and remitting painful diabetic polyneuropathy. Correlations with clinical features and subsequent changes in neurophysiology. AB - Twenty-nine diabetic patients (19 men, 10 women) aged 19-71 yr with newly developed painful polyneuropathy were studied prospectively for 12-18 mo. Pain remitted completely in 16 patients within 12 mo, but continued in the other 13 patients. At presentation, no differences were found in the type or prevalence of symptoms or neurophysiological measurements (electrophysiology and cardiovascular autonomic function tests) between the patients whose pain remitted and those whose pain continued. Most electrophysiological measurements improved slightly in remitting patients but deteriorated slightly in those whose pain continued to reveal a significant difference (P less than .05) between the groups on final review. Similarly, abnormal autonomic nerve function improved slightly when pain remitted but worsened or persisted in patients whose pain continued, again revealing a significant difference between the groups (P less than .05) on final review. We also observed that pain remission usually occurred if the onset of symptoms shortly followed some sudden metabolic change (e.g., rapid improvement in glycemic control, ketoacidosis, anorexia nervosa) when the duration of diabetes was relatively short or when considerable weight loss preceded the onset of pain. We suggest that remitting and chronic painful diabetic polyneuropathy have distinctive clinical features at presentation and detectable neurophysiological differences during their symptomatic evolution. PMID- 3338379 TI - Influence of small-group education sessions on glucose homeostasis in NIDDM. AB - In patients with non-insulin-dependent diabetes mellitus (NIDDM), the influence of knowledge about their disease on the treatment and control of the disease is not clear. We evaluated the efficacy of educational group meetings with NIDDM patients on improving their knowledge of the disease and on disease management. Fifty-one NIDDM patients were randomly assigned to either intervention or control groups. The intervention group participated in courses of three weekly lessons presented by a physician, nurse, and dietitian once every 4 mo. The intervention and control groups were also followed once every 2 mo in the clinic by the same staff. Medical treatment remained unchanged during the study. After a 12-mo follow-up of the intervention group, no significant improvement in their knowledge of diabetes could be demonstrated. However, mean fasting and postprandial blood glucose levels and HbA1c improved significantly in comparison with the control group. The same tendency was evident with the weight and lipoprotein profile. We conclude that educational group therapy can improve diabetes control in patients with NIDDM. PMID- 3338380 TI - Effect of temperament on metabolic control in children with diabetes mellitus. AB - Fifty-one children with insulin-dependent diabetes mellitus (IDDM) and 24 healthy sibling controls were compared on one of two temperament questionnaires completed by parents. Children with IDDM did not provide a characteristic temperament profile or show any problem areas. A regression analysis to predict diabetic control as measured by most recent glycosylated hemoglobin (HbA1c) values revealed that five of the nine temperament scales accounted for a significant 42% of the variance in HbA1c (P less than .001). Children with higher activity levels, greater regularity in routines, milder reactions to external stimuli, distractibility, and negative moods were achieving better glycemic control. The results are discussed in terms of how individual differences in behavioral organization, energy consumption, and stress modulation may affect blood glucose levels. PMID- 3338381 TI - Lower-extremity amputations in NIDDM. 12-yr follow-up study in Pima Indians. AB - The incidence of lower-extremity amputations was estimated in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). Between 1972 and 1984, from a study population of 4399 subjects, lower-extremity amputations were performed on 84 patients, 80 (95%) of whom had NIDDM. Among diabetic subjects, the incidence rate of first lower-extremity amputations was higher in men than in women. Rates increased significantly with increasing duration of diabetes. Presence of medial arterial calcification, retinopathy, or nephropathy; absence of patellar tendon reflexes; impaired great toe vibration-perception threshold; and degree of fasting and 2-h postload hyperglycemia were significant risk factors for amputations. Serum cholesterol concentration, blood pressure, age, and absence of Achilles tendon reflexes were not predictive of amputations. The death rate was greater in diabetic amputees than in diabetic nonamputees of similar age, sex, and duration of diabetes, and a significant increase in cardiovascular deaths was observed in diabetic subjects with amputations. The incidence rate of lower extremity amputations in diabetic Pima Indians is higher than that reported in other diabetic populations. This may reflect differences in risk or a more complete case ascertainment than was possible in previous studies. If the latter is true, the rate of amputations in diabetic individuals may be higher than has been previously appreciated. PMID- 3338382 TI - Consensus on dietary recommendations for NIDDM. PMID- 3338383 TI - [Diagnosis of Paget's disease of bone]. PMID- 3338384 TI - [Therapy of scarlet fever]. PMID- 3338385 TI - [Misplacement of an internal jugular vein catheter]. PMID- 3338386 TI - [Endotoxin contents of phytopharmaceuticals: correlation with clinically observed side effects]. AB - Four phytopharmaceutics (Carnivora, Pascotox forte-Injectopas, Esberitox N, Iascador M), which sometimes cause side effects after parenteral administration (fever, rigor, nausea), were examined for their endotoxin content by the kinetic turbidometric Limulus-amebocyte-lysate (LAL) microtitre test. Contaminations of over 10(5) EU/ml (endotoxin units; 1 EU = 0.1 ng of the FDA standard EC-5) were found in correlation with the clinical picture. In one preparation (Carnivora) very high endotoxin levels were always found; contaminations were only occasionally found in the others. These endotoxin measurements are supported by tests of endotoxin-dependent parameters in in-vivo experiments (reduction in leukocytes, acute death in hyperreactive mice). These findings underline the urgent need for a widening of the regulations on testing for pyrogens to include those parenteral preparations which now do not have to be tested because of their small volume (less than 15 ml). PMID- 3338387 TI - [Evaluation of ST-segment analysis in long-term ECG]. AB - The accuracy of ST-segment analysis by means of the Marquette-Laser-Holter system was compared with conventional ECG registration during ergometry. In 26 patients with angiographically confirmed coronary heart disease conventional chest leads and long-term ECGs were recorded simultaneously during standardized exercise. Simultaneously registered ST-segments in V5 and Holter CM5 were compared, with the results correlating well (r = 0.91) for any recorded abnormal repolarizations. PMID- 3338388 TI - [Hemolytic anemia caused by echinocytosis in liver cirrhosis]. AB - Severe haemolytic anaemia developed in a 34-year-old patient with histologically proven alcoholic liver cirrhosis. While in the blood smear there were only a few acanthocytes, under light-microscopy of EDTA-blood 70% of erythrocytes in the counting chamber were acanthocytes or echinocytes, a finding confirmed under the electromicroscope. It is likely that the echinocytosis and acanthocytosis were the cause of the haemolytic anaemia. Biochemical investigation of the lipid composition of the erythrocyte membrane and of plasma and of the apolipoproteins in plasma revealed a series of changes whose role in haemolysis is discussed. PMID- 3338389 TI - [Adenoma of the papilla of Vater. Diagnostic and therapeutic problems of a rare site for an adenoma]. AB - Intermittent jaundice and recurrent colicky upper abdominal pain in two patients, aged 46 and 48 years, were found by endoscopy to be due to an adenoma of the papilla of Vater. Transduodenal local excision with papilloplasty made both patients free of symptoms. PMID- 3338390 TI - [Can and should we manipulate our LDL receptors?]. PMID- 3338391 TI - [Diagnostic significance of the clonidine suppression test in suspected pheochromocytoma]. AB - A clonidine suppression test and the measurement of the catecholamine (noradrenaline and adrenaline) concentration in 24-hour urine were undertaken on 13 patients with benign phaeochromocytoma (PCC), 30 patients with benign hypertension (BHT) and ten healthy, normotensive volunteers. In 11 patients with PCC (85%) the clonidine suppression test gave true-positive results (no significant suppression of initially raised plasma-catecholamine concentration after oral intake of 300 micrograms clonidine). Continuous fall in plasma catecholamine level after clonidine occurred in two patients with PCC and only moderately elevated initial levels (false-negative results, 15%), as well as in all patients with BHT and all normal controls (true-positive, 100% each). A false negative result for catecholamine concentration in 24-hour urine was obtained in only one patient (8%). In all others there were either true-positive results (urine concentration greater than 200 micrograms/24 h in 12 patients with PCC, 92%) or true-negative results (urine concentration less than 150 micrograms/24 h in all patients with BHT, 100% each). Compared with direct catecholamine measurement in 24-hour urine, the clonidine suppression test did not fulfil the criteria for further investigations in those patients who had moderately raised plasma-catecholamine levels. PMID- 3338392 TI - [Vasculitic neuropathy in the Garin-Bujadoux-Bannwarth syndrome. A contribution to the understanding of the pathology and pathogenesis of the neurological complications in Lyme borreliosis]. AB - Clinical examinations and nerve biopsies were performed on four patients with meningoradiculoneuritis and positive serology for Borrelia (Garin-Bujadoux Bannwarth syndrome). Three patients had a painful multiplex mononeuropathy, while one presented with a picture resembling a Guillain-Barre syndrome. Nerve biopsy in two patients revealed marked perivasculitis, in part with thrombosis of the epineural vasa nervorum. In the other two patients there were small pericapillary infiltrates in the endoneurium with strikingly many plasma cells. These findings speak, on the one hand, for angiopathic-ischaemic nerve damage, but on the other for a local immune reaction to the causative microorganism, because of the plasma rich endoneural infiltrates. The authors suggest that angiopathic-ischaemic tissue lesions and/or local immune reactions may play a role also in the pathogenesis of CNS complications of Lyme disease. PMID- 3338393 TI - [Gastroenterological endoscopy. Current aspects and outlook]. PMID- 3338394 TI - [HIV-2 infection in 2 homosexual German men]. PMID- 3338395 TI - [Viral etiology of Kaposi's sarcoma in AIDS patients?]. PMID- 3338396 TI - [Prophylactic cholecystectomy]. PMID- 3338397 TI - [Cotinine burden of infants due to exposure through passive smoking]. PMID- 3338398 TI - [Epidemiological research on primary hyperparathyroidism. A prospective multicenter study]. AB - Serum calcium determination of 11,588 hospitalized patients during a twelve-month period revealed hypercalcaemia in 74 (0.64%). Further clinical and biochemical investigation established primary hyperparathyroidism in 20 of them (27%), and in 15 (20%) a malignant tumour (with bone metastases in six) as the cause of the hypercalcaemia. Rarer causes were found in 11 patients (15%): diuretic medication (5), lithium treatment (3), immobilization (2) or hyperthyroidism (1). In the remaining 28 patients (38%) no cause of the hypercalcaemia could be established with certainty. In at least six patients, however, there were clinical pointers towards hyperparathyroidism in the absence of unequivocal biochemical findings. Leaving out of account borderline cases, one must reckon on a prevalence of hyperparathyroidism in 0.17% of an unselected group of hospitalized patients. Parathyroid hyperfunction must always be considered in the differential diagnosis because of its manifold clinical presentation. PMID- 3338399 TI - [Melanoma and atopy]. AB - 331 melanoma patients (206 females; 125 males) and 380 control subjects (205 females; 175 males) were questioned about symptoms of atopy (eczema, allergic rhinitis, allergic asthma). Among the melanoma patients there were 14 (10 females, 4 males; 4.2%) with atopy, while in the control group there were 38 (23 females, 15 males; 10%). The influence of age, sex, socio-economic status and other risk factors for melanoma were analysed with the Mantel-Haenszell test, which indicated that melanoma patients had fewer atopic symptoms than subjects in the control group (p less than 0.05). The role of fever may be an explanation of this finding. Among melanoma patients there were fewer feverish infections, while patients with atopy had more feverish complications of their symptoms. PMID- 3338400 TI - [Wall calcifications of the left heart atrium]. AB - The chest X-ray of a 61-year-old man with severe aortic and mitral stenosis revealed extensive, circularly arranged calcifications in the wall of the left atrial appendage. He died soon after admission to hospital and autopsy confirmed the atrial calcifications in association with severe mitral stenosis. Although such calcification of the left atrial wall is rare, it can be of importance because it may make the usual surgical approach to mitral valve replacement impossible. PMID- 3338401 TI - [Toxic psychosis as an acute manifestation of diphenhydramine poisoning]. AB - Acute manifestations of a toxic psychosis with optic and tactile hallucinations developed in a 46-year-old woman after having swallowed a total of 1600 mg diphenhydramine with suicidal intent. The acute hallucinations lasted for eight hours and then disappeared completely without any treatment. The patient reported a series of highly plastic and rapidly changing sensations of various insects, such as spiders, beetles and ticks, without any equivalent in reality, which to the patient seemed absolutely real throughout the psychotic episode. Diphenhydramine intoxication is to be differentiated from two organic psychiatric diseases, the dermatozoa delusion syndrome and alcoholic delirium. PMID- 3338402 TI - [Diagnosis of sarcoidosis]. PMID- 3338403 TI - [Percutaneous endoscopically controlled gastrostomy]. PMID- 3338405 TI - [Serum creatinine levels during antiepileptic treatment]. PMID- 3338404 TI - [Effects of sex steroids on the lipoprotein profile]. AB - Plasma testosterone levels were measured pre- and postoperatively as well as during estrogen substitution in a 47-year-old woman with excessive hyperandrogenaemia due to a Leydig-cell tumour of the left ovary. In addition, the lipoprotein profile was determined before and 14 days after removal of the tumour and four weeks later during estrogen substitution. The preoperative plasma testosterone level was between 6.25 and 8.50 ng/ml; at the same time there was a hypercholesterolaemia with increased beta-lipoprotein and decreased alpha lipoprotein fractions: the ratio of beta- to alpha-lipoprotein cholesterol was 3.0, a type IIa hyperlipoproteinaemia. After the testosterone concentration had returned to normal both the beta- and pre-beta cholesterol fell significantly, while the alpha-lipoprotein fraction remained unaltered. The alpha-cholesterol fraction increased significantly after estrogen substitution, the beta- to alpha lipoprotein ratio being 1.20. It is concluded from these results that hyperandrogenaemia goes together with raised peripheral beta and pre-beta cholesterol concentration, while estrogens cause a rise in the alpha-fraction. PMID- 3338406 TI - The role of the adrenal in generating the diurnal variation in circulating levels of corticosteroid-binding globulin in the rat. AB - Corticosteroid-binding globulin (CBG) levels were measured in serum samples collected sequentially from rats into which indwelling catheters had been inserted. A distinct diurnal variation in CBG levels was found, with the highest levels of binding protein at the beginning of the dark period. CBG levels then decreased until a nadir was reached shortly after the beginning of the light period. To examine the role of glucocorticoid in the generation of this pattern, rats were adrenalectomized 10 days before repeating the experiment. Adrenalectomy abolished both the diurnal variation in CBG levels and the high degree of variation in the levels of binding protein between animals. However, adrenalectomy just before the onset of the dark period did not eliminate the expected decrease in CBG levels. To further explore the role of steroid, animals that had been adrenalectomized for 10 days were given saline containing 25 micrograms/ml corticosterone for a period of 24 h. Despite the attainment of normal plasma corticosterone levels, no decrease in CBG levels was observed. When steroid administration was discontinued, however, CBG levels dropped concurrently with the decreasing steroid. These studies show that a diurnal variation in CBG exists and suggest that it is the result of the diurnal variation in glucocorticoid levels. PMID- 3338407 TI - Preferential saturation of brain 3,5,3'-triiodothyronine receptor during development in fetal lambs. AB - The concentrations of T4 and T3 were measured in brain, liver, and lung of fetal lambs at 100 days gestational age. The highest concentrations of T4 were found in lung (26.8 ng/g). Brain T4 (8.8 ng/g) was only 30% of lung T4. In contrast, higher concentrations of T3 were found in brain (1.8 ng/g) than in lung (0.39 ng/g) or liver (0.36 ng/g). Nuclear T3 was 16% of the total T3 in brain and 44% of that in lung. The degree of saturation of the nuclear T3 receptor was estimated from the concentrations of nuclear T3 and nuclear receptor. Receptor saturation was low in liver and lung (10%) and high in brain (74%). Receptor occupancy was also measured directly in vitro by comparing the binding of [125I]T3 in nuclear extracts at 0 and 20 C. This method is based on the different rates of dissociation of the T3-receptor complex at these temperatures (0.045 and 0.618 h-1, respectively). Therefore, [125I]T3 was bound mainly to unoccupied sites at 0 C, whereas at 20 C it bound to unoccupied sites plus a fraction (70%) of endogenously occupied sites. There was no difference in binding at the two temperatures using lung extract, reflecting a very low occupancy. Data from brain suggested 61% receptor saturation. Total and free T3 were measured in plasma and in lung and brain cytosols, and the figures were compared to the intranuclear free T3 calculated by the law of mass action, from the affinity and saturation of receptor. In lung, the concentrations of cytosolic (5.4 +/- 1.9 pM) and nuclear (8.6 pM) free T3 were similar to that of plasma T3 (3.7 +/- 0.99 pM). In contrast, brain cytosolic (14.9 +/- 1.2 pM) and nuclear (203 pM) free T3 revealed the presence of free T3 gradients from cytosol to plasma (4-fold) and from nucleus to cytosol (13.6-fold). The data suggest that the sheep brain is a major target of thyroid hormone action at the end of the neuroblast proliferation period. Mechanisms are locally present in the brain at this stage of development to ensure a high saturation of the nuclear T3 receptor. PMID- 3338408 TI - Glucocorticoid receptor in magnocellular neurosecretory cells. AB - Quantitative in vitro autoradiography, cytosol receptor assay in punched brain tissue, and immunocytochemistry have revealed that the glucocorticoid receptor is present in the rat supraoptic nucleus (SON). Based on its binding characteristics the receptor appears to be the type II glucocorticoid receptor. With the use of a monoclonal antibody against purified liver glucocorticoid receptor, immunostaining was found in magnocellular neurosecretory neurons in the SON, but not in magnocellular neurons in the paraventricular nucleus. Immunoreactive cells seem to be concentrated in ventral parts of the SON where vasopressin cells were previously shown to be located. One to 2 weeks after bilateral adrenalectomy, there was a substantial decrease in glucocorticoid receptor immunostaining in magnocellular as well as other types of neurons in various brain regions. Administration of synthetic glucocorticoids (RU 28362 or dexamethasone) induced a robust increase in the intensity of immunostaining in cell nuclei of neurosecretory cells. The presence of glucocorticoid receptors in the SON suggests that glucocorticoids may affect vasopressin synthesis or/and secretion through a direct action on magnocellular neurons. PMID- 3338409 TI - Different response to maternal hypothyroidism during the first and second half of gestation in the rat. AB - Female rats were mated and thyroidectomized (T) on the same day and divided into four groups. Three groups were subsequently treated daily with 1.8 micrograms L T4/100 g body wt: 1) for the first 12 days [T + T4 (I)]; 2) from the 12th day until death [T + T4 (II)]; or 3) for the entire 21-day study [T + T4 (I + II)]. The other T animals were maintained without treatment. (T), and another group of mated rats were sham operated (C). Maternal body weight increase during gestation did not differ between T + T4 (I + II) and C dams, whereas it was smaller in T dams from the 7th gestational day onward. Neither interruption of T4 treatment in the T + T4 (I) rats after the 12th day nor treatment initiated at that time in the T + T4 (II) group modified their body weights. At day 21, the weights of the maternal conceptus-free body and liver, the placenta, and the fetuses were lower in the T and T + T4 (II) animals than in either the C and the T + T4 (I + II) animals. Maternal plasma T4 and pituitary GH content were reduced, and plasma TSH was enhanced in both T and T + T4 (I) dams. In fetuses, plasma TSH concentration was augmented in T and T + T4 (I) rats and unchanged in T + T4 (II) animals when compared with those of T + T4 (I + II). Pituitary GH content was reduced in T and T + T4 (II) fetuses and unchanged in the T + T4 (I) group. We propose that maternal thyroidectomy greatly decreases the thyroid hormone levels in embryonic structures during the first half of gestation and inhibits normal maternal metabolic changes during this period. In addition to interfering with normal fetal development, these effects reduce the quantity of maternal substrates available to fetuses during the last phase of gestation. In contrast, when maternal hypothyroidism occurs during the second half of gestation, the effects are not as detrimental because fetal thyroid gland activity is adequate, and maternal catabolic adaptations are not impaired. PMID- 3338410 TI - Progesterone effects on deoxyribonucleic acid synthesis in normal mouse mammary glands. AB - Current in vivo and in vitro data indicate that progesterone (P) is required for epithelial proliferation in mammary glands of adult mice. P receptors (PgR) in adult mammary glands are under estrogenic regulation. By contrast in immature, pubertal 5-week-old mice, PgR are present only in low concentration and cannot be increased by estrogen (E). Having identified two different mammary gland developmental states with differing PgR compositions, the purpose of the present studies was to investigate the roles of E-dependent and -independent PgR in epithelial cell proliferation. DNA histoautoradiography was used to quantitate the effect of P on DNA synthesis; hormonal effects on mammary gland morphology were also assessed. The results demonstrate the P, rather than E, has a major role in stimulating epithelial DNA synthesis in the adult mammary gland. The morphological correlate of P's stimulatory effect on cell proliferation was increased ductal side-branching. We postulate that P is acting via E-dependent PgR and that one important way in which E promotes epithelial cell proliferation in adult tissue is by its ability to increase PgR concentration. In the immature mammary gland E rather than P is primarily responsible for stimulation of epithelial cell proliferation at this developmental stage. It appears likely that the absence of a predominant, P-mediated cell proliferative effect is related to the lack of E-dependent PgR. PMID- 3338411 TI - Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized rats receiving beta estradiol. AB - To examine the interactions between estrogen deficiency and glucocorticoid excess on bone metabolism the osteopenic effects of a standard dose of prednisolone (2 mg/kg BW.day) were studied in sham-ovariectomized (Sham-OVX), ovariectomized (OVX), and OVX rats given replacement beta-estradiol (OVX + E2). For 12 weeks six groups of female albino rats aged 4 months which had their skeletons labeled with 45Ca were fed matched amounts of low-calcium (0.1% Ca) hydroxyproline-free diet. The six treatment groups were: group 1, Sham-OVX; group 2, Sham-OVX + prednisolone; group 3, OVX; group 4, OVX + prednisolone; group 5, OVX + E2; group 6, OVX + E2 + prednisolone. Bone resorption was estimated by studying the urinary excretion of hydroxyproline and 45Ca. Parathyroid function was assessed indirectly from urinary cAMP excretion. Treatments did not influence parathyroid activity or serum levels of calcium or 1,25-dihydroxyvitamin D. However, ovariectomy increased bone resorption and induced osteopenia whereas prednisolone decreased bone resorption and formation and caused osteopenia. Ovariectomy increased the rate of bone resorption in prednisolone-treated rats; prednisolone lowered the rates of bone resorption and formation in OVX rats. The osteopenic effects of prednisolone and ovariectomy were additive and independent. E2 protected bone from the osteopenic effects of ovariectomy but did not affect bone loss induced by prednisolone. These results suggest prophylactic estrogen should help to avoid bone loss from estrogen deficiency in patients requiring chronic high dose glucocorticoid treatment. PMID- 3338412 TI - Effect of birth on plasma testosterone, brain aromatase activity, and hypothalamic estradiol in male and female ferrets. AB - The present studies examined the patterns of circulating testosterone (T) within 0-24 h after birth in male and female ferrets along with concomitant changes in neural aromatase activity and hypothalamic concentrations of estradiol (E2). Plasma and brain samples were obtained 0 and 2 h (cesarean delivery) or 0, 2, 12, and 24 h (natural delivery) after birth. Plasma T levels were significantly higher in male neonates 2 h after birth than at 0 h in both cesarean-delivered (9.48 +/- 1.25 vs. 3.37 +/- 0.60 ng/ml) and naturally delivered (19.28 +/- 2.94 vs. 5.13 +/- 1.93 ng/ml) ferrets, while female neonates showed no significant changes in T over these sampling times. T levels had returned to 0 h levels by 12 h in naturally delivered males. T was significantly lower in females than in males 0, 2, and 24 h after natural delivery, whereas T levels were equivalent in males and females immediately after cesarean delivery. Male kits kept on a heating pad for 2 h after natural delivery had lower plasma T levels than males that were left with their mothers over this same period. Brain aromatase activity in anterior hypothalamus-preoptic area, medial basal hypothalamus (MBH), temporal lobe, and cerebral cortex was equivalent in males and females at all postpartum ages, regardless of whether delivery occurred by cesarean section or naturally. However, in naturally delivered kits of both sexes significant elevations in aromatase activity occurred in MBH and temporal lobe 24 h postpartum. Finally, E2 concentrations in anterior hypothalamus-preoptic area and MBH were equivalent 0 and 2 h postpartum in males and females, regardless of whether they were delivered naturally or by cesarean section. The observed postnatal elevation in T may contribute to brain and behavioral sexual differentiation of male ferrets. It is unclear, however, whether such an effect of T depends on its neural aromatization to E2. PMID- 3338414 TI - Propylthiouracil and methimazole display contrasting pathways of peripheral metabolism in both rat and human. AB - We have developed HPLC procedures for analyzing the metabolites of [35S]methylmercaptoimidazole [( 35S] MMI) and [35S]propylthiouracil [( 35S]PTU) in bile, urine, serum, and liver of rats. We also studied urinary metabolites of [35S] MMI and [35S]PTU in one human subject. In bile collected from [35S]MMI injected rats, two major metabolites accounted for 80-90% of the total 35S. Incubation of these metabolites either with or without beta-glucuronidase led to the appearance of a 35S-labeled compound less polar than MMI. In contrast, the major [35S]PTU metabolite in bile (greater than 50% of total 35S) was completely converted to [35S]PTU on incubation with beta-glucuronidase and showed no conversion in a control incubation. From these results we conclude that the major biliary metabolites of MMI in rats are not glucuronides. They appear to be labile conjugates of a metabolite of MMI. After [35S]MMI injection into rats, two major and at least four minor metabolites were observed in urine. In one human who received [35S]MMI orally, the HPLC profile of 35S in urine was similar to that of the rat. Incubation of human urine or of its isolated major component with beta glucuronidase had no significant effect on the HPLC profile. On the other hand, the major urinary metabolite of [35S]PTU in human and rat urine was completely converted to [35S]PTU on incubation of whole urine with beta-glucuronidase. These results indicate that glucuronides comprise at most only a minor fraction of MMI metabolites in urine of rats or humans. Based on similarities in elution time, the metabolites of [35S]PTU in urine closely resembled those in bile of rats. In contrast, the metabolites of [35S]MMI in urine were strikingly different from those in bile. PTU displays noncovalent binding to serum protein to a much greater extent than does MMI. However, after injection of [35S]MMI into rats, a significant fraction of the 35S was firmly bound to protein in both serum and liver. This binding appeared to be covalent and involved metabolism of [35S]MMI. This type of binding was much less detectable after the injection of [35S]PTU into rats. PMID- 3338413 TI - Persistent viral infection of the thyroid gland: alteration of thyroid function in the absence of tissue injury. AB - The possible role of viruses as the cause of some thyroid disorders was evaluated in three strains of mice neonatally infected with lymphocytic choriomeningitis virus. We report the first definitive evidence that viruses can persist in the thyroid gland, particularly thyroid epithelial cells in which thyroglobulin is synthesized. Concomitant with the infection of these cells was a significant reduction in the level of thyroglobulin mRNA and circulating thyroid hormones. Another virus that causes persistent infection but does not replicate in the thyroid gland failed to alter serum levels of thyroid hormones, indicating the thyroid dysfunction was not a generalized result of stress accompanying a persistent infection. This alteration in thyroid homeostasis during persistent infection with lymphocytic choriomeningitis virus is not caused by autoantibodies to the thyroid. Moreover, despite infection of the thyroid gland, neither necrosis nor inflammation occurs. Thyroid dysfunction was noted both when persistence was initiated at birth and in utero during congenital infection. These observations in an experimental model raise the issue that viruses may play a role in the pathogenesis of some thyroid disorders in man. PMID- 3338415 TI - Altered triiodothyronine metabolism in Zucker fatty rats. AB - Genetically obese Zucker fatty rats require two autosomal recessive genes (fa/fa) to express the obese phenotype. The obese Zucker rat (fa/fa) has decreased total and free serum T3 concentrations, but normal serum T4 concentrations, compared to those in their lean littermates. To elucidate the mechanism of these differences, we measured the MCR and production rate (PR) of T4 and T3 in the three genotypes of 4-month-old male Zucker rats (Fa/Fa, Fa/fa, and fa/fa). In addition, 5' deiodinase activity in liver, kidney, and brown adipose tissue homogenates was determined. T4 MCRs were equivalent in all three genotypes, but a decreased T3 MCR was seen in Fa/fa and fa/fa rats. An additive effect of the fa gene was noted with respect to the decrease in T3 MCR (Fa/Fa, 42.0 +/- 1.5; Fa/fa, 38.7 +/- 2.4; fa/fa, 34.7 +/- 3.4 ml/h; P less than 0.05). Whole body T4 PRs were equal in all three genotypes, but the T3 PR was decreased in the fa/fa rat by 25% compared to that in the homozygous lean rats (15.7 +/- 2.1 vs. 21.2 +/- 2.4 ng/h; P less than 0.005). Liver and kidney 5'-deiodinase activities were decreased in the fa/fa rat by 34% (P less than 0.005) and 20% (P less than 0.01), respectively. Brown adipose tissue and pituitary 5'-deiodinase activity were similar in all three genotypes. These results show a reduction in T3, but not T4, MCR in obese Zucker rats. Whole body T3 production and type I 5'-deiodinase activity were decreased in the obese (fa/fa) rats. These results suggest that decreased T4 to T3 conversion is responsible for the decreased T3 production rate in the fatty rat and may contribute to its obesity. PMID- 3338416 TI - Pituitary and hypothalamic glucose-6-phosphate dehydrogenase: effects of estradiol and age in C57BL/6J mice. AB - Activities of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6-PGDH) were measured in the mediobasal hypothalamus and pituitary gland of C57BL/6J mice throughout their lifespan. Activities of pituitary G6PDH, pituitary 6-PGDH, and hypothalamic G6PDH increase with age in female mice, assayed 7 days after ovariectomy, but not in intact females or males. Pituitary G6PDH specific activity is increased by middle-age (13-14 months) in females, before the onset of acyclicity, and remains elevated throughout the acyclic phases of persistent vaginal cornification and persistent diestrus. This increase in activity is ovary dependent, because it can be prevented by long term (12 month) ovariectomy. The increased activity is not linked to pituitary tumorigenesis and does not result from trapped blood cells, as evaluated by studies with 51Cr-labeled erythrocytes. Responses to physiological levels of estradiol (E2) were analyzed with a graded series of chronic polyethylene implants or after a single sc injection in ovariectomized mice aged 5-22 months. The responsiveness of pituitary G6PDH to E2 is not altered during aging. Young cycling (6 months old) and older acyclic mice (19 months old) displaying persistent vaginal cornification show equivalent increases of about 100% in G6PDH specific activity after chronic E2 treatment and similar time courses of induction after a single E2 injection. Pituitary G6PDH is maximally induced (30% increase) by 48 h after E2 injection in all age groups. In addition, the rates of decline in pituitary G6PDH specific activity after ovariectomy are similar in young and older mice (half-life, 4 days). The specific activity of G6PDH in the mediobasal hypothalamus and blood is unaffected by E2 administration. The relatively low doses of E2 used here fail to alter 6-PGDH specific activity in pituitary or brain. These findings indicate that female reproductive senescence in mice is not associated with generalized losses of sensitivity and responsivity to E2 throughout the neuroendocrine axis. PMID- 3338417 TI - The circadian rhythm of LH release can be shifted by injections of a benzodiazepine in female golden hamsters. AB - Three daily injections of the short-acting benzodiazepine, triazolam, induced pronounced phase shifts in the onset of both the circadian surge in pituitary LH release and the circadian rhythm of locomotor activity in ovariectomized hamsters treated with estrogen. Both the magnitude and the direction of the phase shifts in these two rhythms were similar. These results indicate that a master circadian clock underlying diverse behavioral and endocrine rhythms can be reset by treatment with triazolam. PMID- 3338418 TI - WAIS-R factor structure in epileptic patients. AB - The Wechsler Adult Intelligence Scale--Revised (WAIS-R), the newest version of the Wechsler Scales, has had several factor analytic studies, but none have been done in a sample of seizure-disorder patients. The factor structure of the WAIS-R was examined in this study in a sample of 107 patients with various seizure disorders. The results of this study revealed the 3-factor solution, as has been reported in many previous studies. The most notable difference was the relatively greater prominence of the Freedom from Distractibility factor. These results are consistent with studies of the factor structure of previous editions of the Wechsler Scales in samples of epileptic patients. The relative prominence of the Distractibility factor could suggest that attentional factors are a more important influence on performance than in other patient groups. Further studies are needed to clarify the effect of various seizure-related variables on patterns of intelligence. PMID- 3338419 TI - Right hemisphere partial complex seizures: mania, hallucinations, and speech disturbances during ictal events. AB - A patient with right hemisphere complex partial seizures exhibited extreme emotional lability resembling mania, neologisms resembling those found in fluent aphasia, and hallucinations during ictal periods. The electroencephalographic and clinical findings in this case suggest that cortical and subcortical structures of the right hemisphere may play a role in mediating the expression of language content. PMID- 3338420 TI - Lingual seizures. AB - A 73-year-old patient with hyperglycemia and rheumatoid arthritis presented with attacks of involuntary lingual movements that were associated with pain at the base of the tongue, often followed by aversion of head and eyes to the left with clonic contractions of the left corner of the mouth. Seizures could be induced by a combination of specific movement and somesthetic stimuli. Ictal EEG recording revealed a focal epileptiform discharge in the right centrofrontal area, thus confirming that the patient had lingual seizures, an extremely unusual manifestation. PMID- 3338421 TI - Fragile-X syndrome: a particular epileptogenic EEG pattern. AB - A clinical and EEG study of 12 fragile-X syndrome subjects (six with epilepsy) is presented. All subjects had clinical-family history examinations, EEG evaluations, and karyotyping. Spikes were present in the sleep EEG of one nonepileptic and four epileptic subjects: these spikes were similar in location, occurrence, voltage, frequency, and morphology (and similar to those of the Rolandic spikes). These data, together with the clinical similarities (type of epilepsy, responses to drugs, ages of seizure onset, etc.), have resulted in the postulation of EEG characteristics of epileptic and nonepileptic fragile-X patients. However, further studies with fragile-X patients are needed to confirm this hypothesis. PMID- 3338423 TI - Prolonged electrocerebral silent barbiturate coma in intractable seizure disorders. AB - Barbiturate coma (BC) is a known modality for terminating resistant convulsive status epilepticus. It is usually applied until seizure activity ends. We recently adopted a modified protocol of prolonged, electrocerebral silent BC to treat patients with chronic seizure activity resistant to multiple regimens of antiepileptic drugs. Four patients, aged 4 months to 10 years, with long-standing intractable generalized seizures were treated. Seizure frequency ranged from one to two to numerous times per day. Following BC, one patient has been seizure free during 8 months of follow-up, and another has had only two seizures in 18 months. A 4-month-old infant was seizure-free for 2 weeks after BC and then died from underlying CNS disease. A 10-year-old girl died during BC from shock and hyperpyrexia. The results obtained in our patients indicate that prolonged electrocerebral silent BC may exert a beneficial long-term effect in treatment of intractable seizure disorders. This procedure might also be beneficial in other forms of epilepsy. PMID- 3338422 TI - Hot-water epilepsy: a variant of reflex epilepsy in southern India. AB - "Hot water epilepsy" (HWE), precipitated by a bath or shower in hot water, has been described infrequently in the literature. We report 279 cases of HWE that were seen between 1980 to 1983 in Bangalore, South India. We found HWE to be more common in children, with cases more frequent among male than female patients (2.6:1). Complex partial seizures constituted the main clinical presentation (67.0%); HWE accounted for 4.4% of all complex partial seizures and generalize tonic-clonic seizures seen at our center during the 1980-1983 period. Although prognosis seems favorable 25.4% of our patients developed nonreflex epilepsy within 1-3 years. They were managed with antiepileptic drugs and the use of lukewarm water for bathing. PMID- 3338425 TI - Focal medial temporal lobe spike-wave complexes evoked by a memory task. AB - Several factors are known to modulate the occurrence of interictal spike-wave complexes (SWC). During performance of a recent memory task by a patient with uncontrolled complex partial seizures and implanted electrodes, visually presented stimuli consistently evoked focal medial temporal lobe interictal SWC with an average latency of 228 +/- 29 ms. The SWC were more often lateralized to the left medial temporal lobe. No consistent change in interictal spike rate was observed during performance of several other cognitive tasks during which visual or auditory stimuli were presented. This suggests that performance of specific cognitive tasks--in this case, recognition memory of words--can trigger interictal SWC. PMID- 3338424 TI - Decrease of serum folates in healthy male volunteers taking phenytoin. AB - The effect of phenytoin (PHT) on serum folate and the effect of additional oral folic acid (FA) on serum folate during continued treatment with PHT were studied in 13 healthy male subjects 20-35 years of age. The study was divided into two phases: Phase I determined Vmax (mg/kg/day) and Km (microgram/ml) of PHT in order to calculate the PHT doses needed for the second phase. Phase II was a four-way cross-over study to examine the effect of 1 and 5 mg FA on total serum PHT concentrations 1 microgram/ml less and 5 micrograms/ml greater than the subject's Km, Km-1 and Km+5, respectively. Both phases examined the effect of PHT on serum folate. In Phase I, serum folate decreased by a mean and standard deviation of 42.15 +/- 21.44% after an average of 24.15 +/- 5.63 days of PHT administration, with a mean steady-state total serum PHT concentration of 8.45 +/- 2.70 micrograms/ml. Mean percentage decreases in serum folate before the addition of 1 and 5 mg FA in Phase II were 12.80 +/- 31.45% and 23.24 +/- 21.24% for Km-1 and Km+5, respectively. The average numbers of days of PHT administration and total serum PHT concentrations before FA administration were 9.52 +/- 3.34 and 15.84 +/ 7.02 days, and 2.60 +/- 2.18 and 8.64 +/- 3.44 micrograms/ml, for Km-1 and Km+5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338427 TI - Immunoreactive leucine-enkephalin content in brains of epileptic E1 mice. AB - The immunoreactive leucine-enkephalin (IR Leu-E) content in the brains of epileptic E1 mice was determined. E1 mice are mutants from the dd strain of mice and are susceptible to convulsions. Seizures were elicited in E1 mice by repeated postural stimulations. As controls, ddY strain (nonconvulsive) mice and nonstimulated E1 mice (which had not developed convulsions) were used. IR Leu-E content was measured by radioimmuno-assay. Before the convulsion, the IR Leu-E content in the striatum of E1 mice was 60% of the content in the controls. In the hypothalamus, IR Leu-E levels were increased by 85% 45 min after a convulsion. IR Leu-E was also increased in the striatum (176% of preconvulsive state), cortex (121%), medulla oblongata + pons (132%), hypothalamus (180%), and midbrain (159%) 48 h after a convulsion. PMID- 3338426 TI - Pharmacological effects of enantiomers of 4-amino-N-(alpha methylbenzyl)benzamide, a chemically novel anticonvulsant. AB - LY 188544,S,R-4-amino-N-(alpha-methylbenzyl) benzamide, and its two stereoisomers are structurally novel anticonvulsants. The anticonvulsant profile of LY 188544 after intraperitoneal administration to mice was determined in standard anticonvulsant tests: maximal electric shock (MES), strychnine tonic-extensor, and threshold tests using pentylenetetrazol, picrotoxin, and bicuculline. In this series of tests, LY 188544 had good activity in the MES test and some activity in the three threshold tests. Thus, its profile of activity was most similar to that of phenobarbital, and less similar to that of phenytoin and carbamazepine. After oral administration to mice and rats, LY188544 was effective in the MES test, but did not provide complete protection in the threshold pentylenetetrazol test. When the individual stereoisomers, LY188545 (S isomer) and LY188546 (R isomer), were evaluated after oral administration, LY188545 was 2.2 times more potent than LY188546 against MES-induced seizures. However, when evaluated after intravenous administration, the potency difference was only 1.1. LY188546 was the least toxic in terms of neurological impairment. All compounds had good protective indexes (ratio between doses for neurological impairment and doses for anticonvulsant efficacy in the MES test). LY188545 and LY188546 potentiated hexobarbital sleeping time after acute administration but not after chronic (4-day) administration. Tolerance did not develop to the effects of LY188546 on MES or neurological impairment after 4 days of administration. These results suggest that LY188546 is a chemically novel anticonvulsant with a promising pharmacological profile. PMID- 3338428 TI - Psychological reactions to air pollution. AB - Interviews with a large representative sample of Los Angeles residents reveal that these citizens are somewhat aware and concerned about air pollution, but not knowledgeable about its causes. Direct behaviors to reduce causes of pollution or one's exposure to it are rare. A moderate percentage of people seek out information about air pollution or complain about it. Fewer follow state health advisories by reducing automobile driving or restricting activity during air pollution episodes. Preliminary modeling of citizen compliance with air pollution health advisories suggest that personal beliefs about negative health effects are a important predictor of compliance. Finally, modest but significant relationships are noted between ambient photochemical oxidants and anxiety symptoms. The latter finding controls for age, socioeconomic status, and temperature. PMID- 3338429 TI - Fluorocarbon-enhanced mutagenesis of polyaromatic hydrocarbons. AB - The widely used fluorocarbon refrigerant and cleaning solvent 1,1,2-trichloro 1,2,2-trifluoroethane (Freon TF), though generally considered biologically inert, enhances the metabolic activation of chemical carcinogens. Liver microsomal extracts from mice given single intraperitoneal injections of this fluorocarbon showed significant increases in their ability to activate carcinogenic polyaromatic hydrocarbons to form mutagens, compared to control mice injected with saline. Polyaromatic hydrocarbons aminofluorene and acetylaminofluorene were activated in this way. Mutagenicity was measured by a microbial assay. Both commercial grade and redistilled fluorocarbons gave similar results, that is, more highly active liver extracts after administration of the fluorocarbon preparation to mice. Neither industrial grade nor redistilled preparation was itself mutagenic. A combined liver microsomal extract from mice breathing Freon TF at 20,000 ppm in air for 8 hr also had enhanced ability to activate aminofluorene as a mutagen. Exposing mice to Freon TF by inhalation more closely matches the normal route of human exposure to fluorocarbons. The results of this study imply that low-molecular-weight fluorocarbons may pose a carcinogenic risk by acting as cocarcinogenic enhancers of carcinogen activation. The possibility that fluorocarbons are cocarcinogens in this way has apparently not been heretofore considered. PMID- 3338430 TI - Lacinilene C methyl ether (LCME) constricts tracheal smooth muscle. AB - Lacinilene C methyl ether (LCME) is a constituent of the cotton plant and has been implicated as a causative agent of byssinosis. The effect of synthetic LCME on the behavior of isolated strips of canine tracheal smooth muscle (TSM) was examined in tissue bath experiments. LCME (0.64-6.6 x 10(-4) M) caused slowly developing but strong and sustained contractions of TSM strips. Blockade of acetycholine, 5-hydroxytryptamine (5-HT), and histamine H1 receptors with atropine, methysergide, and pyrilamine, respectively, had no effect on constrictions induced by LCME. In contrast, the calcium channel antagonist, verapamil, significantly reduced the response to LCME. Moreover, addition of the beta receptor agonist, isoproterenol, at the peak of LCME-induced contractions relaxed tissues in a concentration-dependent manner. We conclude that LCME elicits contraction of TSM by enhancing the movement of calcium through potential dependent channels of smooth muscle cell membranes. This mechanism of action does not require activation of specific membrane receptors for acetylcholine, 5-HT, and histamine. PMID- 3338431 TI - Persistent free radicals in the smoke of common household materials: biological and clinical implications. AB - We have detected free radicals in the gas-phase smoke resulting from the combustion of several household materials. Materials were pyrolyzed by rapid heating in a quartz ignition tube in a flowing air stream. The filtered smoke was bubbled into a dodecane solution of alpha-phenyl-N-t-butylnitrone (PBN), and the resulting nitroxide radicals were detected by electron spin resonance. Cellulosic materials (birch plywood, cellulose, 1R1 research cigarette tobacco, and yellow pine) and dried exterior paint produce about the same yield of trapped radicals. The smoke from polyethylene and rubber produce approximately 2-fold more radicals than the smoke from the cellulosic materials. Nylon smoke yields about 10-fold less radicals than the cellulosic materials. The smokes from polyvinyl chloride and polytetraflouroethylene do not produce detectable spin adducts of PBN by this method. Where radicals were trapped, oxygen-centered spin adducts predominated; lesser amounts of carbon-centered spin adducts and an oxidation product of PBN were observed. Different oxygen-centered radicals were detected from different materials, as judged from the variation observed in the hyperfine splitting constants of the principal spin adducts. When cellulose smoke is dissolved in solution, radicals continue to be produced for at least 20 min, suggesting the production of a metastable species in the gas phase that decomposes to form radicals in solution. PMID- 3338432 TI - Human glutathione peroxidase activity in cases of high selenium exposures. AB - Four communities with water supplies having selenium concentrations of less than 3.1, 1.7, 189, and 496 micrograms/liter were selected for study. Samples of blood, urine, and tap water were obtained from participants in each community and analyzed for selenium content. Blood samples were also analyzed for glutathione peroxidase activity. Results showed an increase in selenium concentration in the urine as the water selenium increased. Selenium concentrations in blood did not reflect the increased selenium exposure. Glutathione peroxidase activity in whole blood decreased in highly exposed participants compared to those with low exposure. We conclude that glutathione peroxidase activity in cases of possible environmental toxic exposures will not show the increased activity seen in supplementation of selenium to deficient subjects. PMID- 3338433 TI - Prevalence of respiratory symptoms and diseases in schoolchildren living in a polluted and in a low polluted area in Israel. AB - Second and fifth grade schoolchildren living in two communities with different levels of air pollution were studied. The parents of these children filled out ATS-NHLI health questionnaires. The prevalence of reported respiratory symptoms and pulmonary diseases was found to be significantly higher among children growing up in the polluted community (Ashdod) as compared with the low-pollution area (Hadera). Logistic models fitted for the respiratory conditions which differed significantly between both areas of residence also included background variables that could be responsible for these differences. Relative risk values, which were calculated from the logistic models, were in the range of 1.47 for cough without cold to 2.66 for asthma for children from Ashdod, as compared with 1.00 for children from Hadera. PMID- 3338434 TI - Environmental factors in the etiology of neural tube defects: a negative study. AB - A case-control study was made on women who had an infant with a neural tube defect and twice as many controls. Cases and controls were selected from a national medical birth registry from which prospectively collected data on previous pregnancy, contraceptive use, and smoking were also retrieved. Women's occupation was either retrieved from that registry or from census information which was partially checked with direct interview. Information on environmental characteristics of the place of living of the women in early pregnancy was given by field workers who were unaware of the status of case or control. Cases and controls showed no statistically significant difference with regard to previous pregnancies and use of contraceptives at or the month before the time of conception. Case women smoked 10 cigarettes or more a day slightly more often than control women did but the difference was not statistically significant. No statistically significant difference in occupation distribution was seen between cases and controls (but cases had slightly more occupations where chemical exposure is likely), and no differences in home environment could be found. It is concluded that the factors studied play no major etiological role for the origin of neural tube defects in Sweden. PMID- 3338435 TI - Assessment of mercury presence and exposure in a lighthouse with a mercury drive system. AB - It is common practice for lighthouses with large Fresnel lenses to use mercury baths as a low-friction rotation mechanism. Some recent acute mercury poisonings and incidents of abnormal behavior in lighthouse keepers have drawn attention to the potential for chronic mercury poisoning in these workplaces. This study evaluated the distribution of mercury in a lighthouse on the Canadian west coast, and the exposure of its keepers and their spouses under two weather conditions. The urine mercury levels found in the lighthouse personnel were all less than would be expected in an occupationally exposed group (less than 4 micrograms/24 hr urine). Air concentrations in the lighthouse ranged from 4.4 to 26.3 micrograms/m3. Swabbing showed considerable accumulation of mercury on surfaces in the area of the light rotation mechanism, as well as transport throughout the lighthouse. The mercury levels in this lighthouse appeared to be under control through effective convective ventilation and employee awareness. The study signals potential problems where precautions have not been taken, especially in situations where the keepers and their families live in the lighthouse. PMID- 3338436 TI - Association of lung cancer and airway particle concentration. AB - Using 15 autopsy lungs containing nonresected lung cancers, we evaluated the exogenous mineral particle content of the upper and lower lobe parenchyma and of the upper and lower lobe bronchial mucosa. The bronchial mucosa from the lobe with the cancer was found to contain about three times the median mineral particle load of the bronchial mucosa from the lobe without the cancer, a statistically significant difference. No such difference was seen for mineral content of the parenchyma. This observation suggests that mineral particle deposition or accumulation in the bronchial mucosa may be related to respiratory carcinogenesis. PMID- 3338437 TI - Comparison of blood toluene levels after inhalation and oral administration. AB - The purpose of this investigation was to compare blood toluene levels in Sprague Dawley rats after oral and inhalation administration. Groups of 30 rats were dosed by gavage with 86.7, 217, 433, or 867 mg toluene/kg body wt or exposed for up to 6 hr, 5 rats per exposure, to an atmosphere of either 200 or 1000 ppm toluene. Blood was sampled by cardiac puncture from 5 rats in each of the six dose groups at 0.5, 1.0, 2.0, 4.0, 6.0, and 24.0 hr after gavage dosing or the beginning of the inhalation exposure. Blood toluene levels were analyzed. A four parameter model was fitted to the blood toluene levels of the orally dosed rats. The area under the curve generated by this model, representing total blood toluene concentration over 6 hr, was calculated and compared to the area under the blood toluene curve for the 6-hr inhalation exposure. Integrated areas from the two routes of exposure were used for direct comparison of oral and inhalation exposures. The data demonstrate that gavage dosing can be used to approximate inhalation exposure to toluene. PMID- 3338438 TI - Effects of cadmium on natural killer and killer cell functions in vivo. PMID- 3338440 TI - Cytogenetic and chemical detection of human exposure to polyhalogenated aromatic hydrocarbons. AB - Peripheral lymphocytes from Taiwanese women (n = 35) exposed to polychlorinated aromatic hydrocarbons and from matched controls (n = 24) were assessed for the levels of sister chromatid exchanges (SCEs) after a 72-hour incubation of whole blood in the presence or absence of alpha-naphthoflavone (ANF) and for chromosome aberrations after 48 hours of incubation. Serum levels of polychlorinated biphenyl (PCB) congeners were measured for all individuals, and serum levels of several polychlorinated dibenzofurans (PCDFs) were measured for 12 exposed individuals by gas chromatography-mass spectometry. Blood concentrations of total PCBs in the exposed population averaged approximately 15 ppb, whereas mean PCDF values were 14 ppt. Major PCB congeners detected were 2,2' 4,4', 5,5'-hexa CB and 2,2'3,4,4',5-hexa CB. PCDFs detected were primarily 1,2,3,4,7,8, hexachlorodibenzofuran (10.8 ppt) and 2,3,4,7,8-pentachlorodibenzofuran (2.7 ppt). Average SCE frequencies were 7.61 for controls and 7.30 for exposed individuals when assays were conducted in the absence of ANF, whereas respective values were 8.85 and 10.75 in the presence of ANF. Differences in the level of ANF-induced SCEs between the two populations were highly significant (P less than .001). Moreover, the ANF-induced SCEs were highly correlated with the serum concentrations of total PCBs and of several PCB congeners (P less than .001). Increases in ANF-induced SCEs appeared to be linear up to a PCB concentration of approximately 30 ppb. Chromosome aberration frequencies were similar in control and exposed populations. These studies demonstrate that in vivo exposure to PCBs and PCDFs result in an enhanced sensitivity of lymphocytes to the SCE-causing actions of ANF. PMID- 3338439 TI - Induction of hepatic drug-metabolizing enzymes in rats treated with 1 nitropyrene. AB - The inducing effects of 1-nitropyrene (1-NP) on the microsomal cytochrome P-450 system were studied in rats. Intraperitoneal administration of 1-NP led to increases in cytochrome P-450 content and aryl hydrocarbon hydroxylase, ethoxycoumarin, and ethoxyresorufin-O-deethylase activities. These increases were dose dependent. Cytochrome b5 content and aminopyrine and p-nitroanisole demethylase activities were not affected by treatment of rats with 1-NP. Substrate specificity, sensitivity to mixed-function oxidase inhibitors, and electrophoretic pattern of 1-NP-induced cytochrome(s) P-450 were compared to the major forms of cytochrome P-450 induced by phenobarbital and methylcholanthrene. Furthermore microsomes from 1-NP-induced rats showed greater ability to metabolize the chemical as compared with those from control animals; this result indicates that 1-NP induces a form(s) of cytochrome P-450 especially effective in the metabolism of the substance itself. PMID- 3338441 TI - Genotoxicity of acrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate in L5178Y mouse lymphoma cells. AB - A series of monomeric acrylate/methacrylate esters (methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate) as well as acrylic acid were examined for genotoxic activity in L5178Y mouse lymphoma cells without exogenous activation. All five compounds induced concentration-dependent increases in mutant frequency. Small-colony, trifluorothymidine-resistant mutants were primarily induced, which suggests that these compounds may act via a clastogenic mechanism. This prediction was confirmed by the finding that all five compounds produced gross chromosome aberrations in mouse lymphoma cells. The two acrylates were much more potent in their response than acrylic acid. Methyl acrylate (22 micrograms/ml, survival = 18%) induced 385 mutants/10(6) survivors (total mutant frequency less the spontaneous mutant frequency) and 45 chromosome aberrations/100 cells analyzed (total aberrations less the spontaneous background). Ethyl acrylate (37.5 micrograms/ml, survival = 15%) induced 683 mutants/10(6) survivors and 48 aberrations/50 cells analyzed. Acrylic acid (500 micrograms/ml, survival = 22%) induced 245 mutants/10(6) survivors and 37 aberrations/100 cells analyzed. The two methacrylates required higher concentrations to induce a positive response. Methyl methacrylate (2,799 micrograms/ml, survival = 11%) induced 230 mutants/10(6) survivors and 29 aberrations/200 cells analyzed. Ethyl methacrylate was extremely difficult to test because of a plateau in the dose response, over which the toxicity fluctuated from 2% to 37% survival. Positive responses (twice the spontaneous background) were only obtained at toxicity levels with less than approximately 20% survival. A concentration of 1,626 micrograms/ml (survival = 16%) induced 83 mutants/10(6) survivors and 11 aberrations/200 cells analyzed. The evidence suggests that the genotoxicity of these compounds is most likely due to a clastogenic mechanism. PMID- 3338442 TI - Responses of the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay. II: 18 coded chemicals. AB - Eighteen chemicals were tested for their mutagenic potential in the L5178Y tk+/- mouse lymphoma cell forward mutation assay by the use of procedures based upon those described by Clive and Spector [Mutat Res 44:269-278, 1975] and Clive et al [Mutat Res 59:61-108, 1979]. Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Significant responses were obtained with benzofuran, benzyl chloride, bromodichloromethane, butylated hydroxytoluene, chlorendic acid, o chlorobenzalmalonitrile, 1,2,3,4-diepoxybutane, dimethyl formamide, dimethyl hydrogen phosphite, furfural, glutaraldehyde, hydroquinone, 8-hydroxyquinoline, and resorcinol. Apart from bromodichloromethane, butylated hydroxytoluene and dimethyl hydrogen phosphite, rat liver S9 mix was not a requirement for the activity of any of these compounds. Chemicals not identified as mutagens were water, tert-butyl alcohol, pyridine, and witch hazel. PMID- 3338443 TI - Pattern of cardiac diseases in an Ethiopian children's hospital. PMID- 3338444 TI - Relation between urine and blood glucose in adult Ethiopian diabetics. PMID- 3338445 TI - Prevalence of mitral valve prolapse in 98 presumably healthy young Ethiopians. PMID- 3338446 TI - Leukaemia in a children's hospital, Addis Ababa. PMID- 3338447 TI - Amyloid nephrotic syndrome in an 8-year-old boy: a case report. PMID- 3338448 TI - Purification and characterization of peptide-elongation factor 2 (aEF-2) from an extremely halophilic archaebacterium Halobacterium halobium. AB - A procedure is described for the purification of the archaebacterial peptide elongation factor 2 (aEF-2) from an extremely halophilic archaebacterium Halobacterium halobium. The enrichment was about 530-fold, the obtained preparation practically homogeneous as judged by SDS-PAGE. The poly(U)-dependent poly(Phe) synthesis was completely dependent on aEF-2 in the presence of partially purified aEF-1, and the activity was equivalent to a poly(Phe) synthesizing system containing unfractionated S-100 enzymes. aEF-2 consists of a single peptide with a relative molecular mass of 125,000 +/- 3000 and 100,000 +/- 3000 as determined by SDS-PAGE and gel filtration on Sephadex G-200 respectively. The isoelectric point was 5.7. The amino acid composition analysis indicated the predominance of acidic amino acids (aspartic acid and glutamic acid) and the low content of hydrophobic amino acid (phenylalanine) as compared with those of eukaryotes and prokaryotes. The factor was stable in a pH range from 6 to 8. 2 Mercaptoethanol and GTP but not GDP markedly protected aEF-2 from heat denaturation at 52 degrees C. aEF-2 became inactivated and insensitive to ADP ribosylation by diphtheria toxin at low ionic strength but could be renatured by increasing ionic strength. Obviously higher concentrations of salts contribute to the conformational stability of aEF-2. PMID- 3338450 TI - Two-dimensional 1H-NMR studies of the solution structure of plasminogen kringle 4. AB - Native kringle 4 from human plasminogen has been studied by two-dimensional 1H NMR methods in order to obtain new structural information about the kringle fold. Two-dimensional scalar correlated spectroscopy (COSY), two-dimensional dipolar correlated spectroscopy (NOESY) and two-dimensional relayed coherance transfer spectroscopy (RCT) experiments were recorded, allowing most resonances arising from the aromatic and methyl-containing residues to be assigned in the spectrum. From an analysis of NOE data, a small segment of double-stranded beta-sheet has been identified near residues Phe63 and Thr64. Further analysis of the NOESY spectrum has allowed detailed study of the conformation of sidechains located in regions near Leu45 and Val69. A model has been constructed of the polypeptide segment comprising residues 40-49 which accounts for the observed NOE interactions. PMID- 3338449 TI - cDNAs for canavalin and concanavalin A from Canavalia gladiata seeds. Nucleotide sequence of cDNA for canavalin and RNA blot analysis of canavalin and concanavalin A mRNAs in developing seeds. AB - By a method of Escherichia coli expression-vector-primed cDNA synthesis, a cDNA expression library was constructed from total poly(A)-rich RNA that was prepared from immature embryos of Canavalia gladiata. Essentially full-length cDNA clones for two seed proteins, canavalin and concanavalin A, were selected from the library by immunological screening of the colonies and in vitro RNA synthesis and translation. The complete amino acid sequence of canavalin was determined from the nucleotide sequence of the corresponding cDNA and was found to be very homologous to 7S seed proteins of other legumes. The nucleotide sequence of the cDNA predicts a 26-amino-acid extension in the precursor at the amino terminus of the mature canavalin. Canavalin mRNA and concanavalin A mRNA levels at successive stages of the seed development were estimated by RNA blot hybridization and results indicated that the two mRNA levels are differently regulated. PMID- 3338451 TI - Analysis of the aliphatic 1H-NMR spectrum of plasminogen kringle 4. A comparative study of human, porcine, bovine and chicken homologs. AB - The aliphatic 1H-NMR spectrum of the kringle 4 domain of human plasminogen has been studied via two-dimensional chemical shift correlated (COSY) and nuclear Overhauser correlated (NOESY) experiments at 300 MHz and 620 MHz. A number of aliphatic proton spin systems have been identified and several definite assignments have been made. This was mainly achieved by comparison of the human kringle 4 spectrum with spectra of the porcine, bovine and chicken homologs and also with that of the kringle 1 from human plasminogen on which we have reported previously. The three valyl and two leucyl residues of human kringle 4 have been assigned. The eleven threonyl spin systems have been identified via a RELAYED COSY experiment and Thr17 has been assigned. The three alanyl spin systems have been identified and assigned. Six seryl spin systems have been identified and the signals from the seven glycyl residues of human kringle 4 have been located with Gly45 assigned. Furthermore, 24 AMX spin systems have been mapped in the COSY spectrum of human kringle 4 and H alpha-H beta,beta' spin systems of Tyr2, Tyr41, Tyr50, Tyr74, Trp25 and Trp62 have been assigned. From the spectrum of a deglycosylated chicken homolog, the epsilon-methyl singlets of Met28 and Met48 have been assigned. Finally, ligand effects on selected aliphatic resonances were observed which could be analyzed in terms of residues likely to neighbor the kringle lysine-binding site. PMID- 3338453 TI - Studies of the cellulolytic system of Trichoderma reesei QM 9414. Analysis of domain function in two cellobiohydrolases by limited proteolysis. AB - Limited action of papain on the native forms of two cellobiohydrolases (CBH) from Trichoderma reesei (CBH I, 65 kDa, and CBH II, 58 kDa) leads to the isolation of the respective core fragments (56 kDa and 45 kDa) which are fully active on small, soluble substrates, but have a strongly reduced activity (respectively 10% and 50% of the initial value) on microcrystalline cellulose (Avicel). By partial sequencing at the C terminus of the CBH I core and at the N terminus of the CBH II core the papain cleavage sites have been assigned in the primary structures (at about residue 431 and 82 respectively). This limited action of papain on the native enzymes indicates the presence of hinge regions linking the core to these terminal glycopeptides. The latter conserved sequences appear either at the C or N terminus of several cellulolytic enzymes from Trichoderma reesei [Teeri et al. (1987) Gene 51, 43-52]. The specific activities of the intact enzymes and their cores on two forms of insoluble cellulose (crystalline, amorphous) differentiate the CBH I and CBH II in terms of adsorption and catalytic properties. Distinct functions can be attributed to the terminal peptides: for intact CBH II the N terminal region contributes in the binding onto both cellulose types; the homologous C-terminal peptide in CBH I, however, only affects the interaction with microcrystalline cellulose. It could be inferred that CBH I and its core bind preferentially to crystalline regions. This seems to be corroborated by the results of CBH I/CBH II synergism experiments. PMID- 3338452 TI - Interactions of fatty acids with neutral fatty-acid-binding protein from bovine liver. AB - Hepatic-type fatty-acid-binding protein (hFABP) from the cytosol of bovine liver is a 14.4-kDa neutral protein with a blocked N-terminus and a disulfide system located on the surface of the protein. It binds two molecules of fatty acid in one binding site, apparent dissociation constants of the oleic acid/hFABP complex are 0.24 microM and 2.15 microM. Computer analysis of circular dichroic spectra predicts that hFABP contains about 12% alpha-helix, 45% beta-structure, 15% beta turn and 27% unordered structure. Ellipticities indicative of secondary structure are not affected by fatty acid binding. Cationic amino acid residues of hFABP (1 His, 15 Lys, 2 Arg) were screened for ionic fatty acid/protein interactions. His was excluded, as 1H-NMR analysis of His-C2 and His-C4 protons indicated that binding of oleic acid shifts the pK of His from 6.9 to 7.1 only in hFABP with the disulfide system in the oxidized state; acylation of His with diethylpyrocarbonate does not affect the binding of the fatty acid. Acetylation of Lys reduces binding marginally, whereas modification of Arg with phenylglyoxal lowers the binding activity by 65%. From 1H-NMR investigations, conformational changes within the protein, due to a sort of disaggregation of hFABP upon fatty acid binding, were derived. Most of the proton resonances sharpen up with ligand binding, and some of the methyl resonances shift positions, possibly because they are directly involved in the fatty acid/protein interaction. PMID- 3338454 TI - Characterization of the actin polymerization-inhibiting protein from chicken gizzard smooth muscle. AB - An actin polymerization-inhibiting protein, occurring in crude preparations of vinculin from chicken gizzard, has been found to be heterogeneous. The molecular masses of the polymerization-inhibiting peptides have been reported to range from 20 kDa to 80 kDa [Schroer, E. & Wegner, A (1985) Eur. J. Biochem. 153, 515-520]. In this paper, a 21-kDa peptide was isolated from the bulk of the other peptides by gel chromatography. The 21-kDa peptide was identified as a polymerization inhibiting peptide by its ability to retard nucleated actin polymerization and to bind polymeric actin when it was blotted onto nitrocellulose. Antiserum raised to the 21-kDa peptide was found to react with almost all peptides of the blotted heterogeneous polymerization-inhibiting protein. The same peptides which reacted with antiserum cosedimented with polymeric actin. The major peptides of the blotted polymerization-inhibiting protein bound polymeric actin. The largest peptide which reacted with antiserum and cosedimented with polymeric actin had a molecular mass of 85 kDa. The results suggest that the preparation of polymerization-inhibiting protein contains mainly polymerization-inhibiting peptides and only some contaminants, and that all the polymerization-inhibiting peptides are proteolytic fragments stemming from a common precursor. PMID- 3338455 TI - Reconstitution of myoglobin from apoprotein and heme, monitored by stopped-flow absorption, fluorescence and circular dichroism. AB - The reconstitution reaction of ferric cyanomyoglobin from apomyoglobin and hemin dicyanide was investigated with a stopped-flow apparatus by the use of five kinds of probes; (a) Soret absorption, (b) fluorescence quenching of tryptophan, (c) far-ultraviolet CD, (d) near-ultraviolet CD, and (e) Soret CD. After mixing of apomyoglobulin with equimolar amounts of hemin dicyanide, the Soret absorption band was shifted to longer wavelengths within 10 ms. The shifted band kept its shape for a few seconds, and then gradually shifted to shorter wavelengths. A rate constant of the slow reaction was 1.1 x 10(-2) s-1. Time courses of fluorescence quenching followed a second-order reaction with a rate constant of 9 x 10(7) M-1 s-1. Far-ultraviolet CD recovered to the level of native state within the response time of an apparatus (= 64 ms). Near-ultraviolet CD and Soret CD changed with first-order rate constants of 5-30 s-1 and 5 x 10(-3) s-1 respectively. On the basis of the kinetic results we propose the following reconstitution pathway of myoglobin. Apomyoglobin has essentially a highly folded structure similar to myoglobin, but there are some differences in the secondary structure between them. In the first step, heme enters the pocket-like site of apomyoglobin and interacts with surrounding hydrophobic residues in the pocket, and then the interaction may give a complete ordered structure to the protein. Second, the tertiary structure of the heme pocket is partly constructed. Third, the iron-proximal His bond occurs, followed by the attainment of the final conformation. This sequence of the events shows that the polypeptide chain is entirely folded before the completion of three-dimensional structure of the heme pocket. The reconstitution pathway is fairly different from that of the alpha subunit of hemoglobin reported by Leutzinger and Beychok [Proc. Natl Acad. Sci. USA (1981) 78, 780-784], which described how a drastic recovery in helicity was observed on the heme-binding, and that the recovery is introduced by the formation of the heme pocket structure. The difference in the results found for the alpha subunit and myoglobin suggests a difference in conformation: in apomyoglobin most of the helices are arranged and folded around a helix core to form a compact structure as a whole, while in apo-alpha subunit some helices are not folded around the helix core. Helix D, which is absent in the alpha subunit, may play an important role in folding of the helices. PMID- 3338456 TI - The primary structure of the basic isoform of Acanthamoeba profilin. AB - Acanthamoeba profilin-II [Kaiser, D.A., Sato, M., Ebert, R. F. and Pollard, T.D. (1986) J. Cell. Biol. 102, 221-226] was digested with trypsin or cleaved by 2-(2 nitrophenylsulphenyl)-3-methyl-3-bromoindolenine. The tryptic peptides were purified by reversed-phase-high-performance liquid chromatography and completely sequenced using automated gas-phase sequence analysis. The complete profilin-II sequence was deduced by ordering the tryptic peptides using the sequence information of the tryptophan-cleavage products. Acanthamoeba profilin-II was found to be homologous to the previously determined profilin-I sequence [Ampe, C., Vandekerckhove, J., Brenner, L., Tobacman, L. and Korn, E.D. (1985) J. Biol. Chem. 260, 834-840]. Like profilin-I, profilin-II consists of 125 amino acids, has a blocked NH2 terminus and a trimethyllysine residue at position 103. Profilin-II differs in at least 21 positions from one of the profilin-I isoforms. The amino acid exchanges are mainly concentrated in the middle part of the sequence. Profilin-II contains two more basic residues than profilin-I, which explains its higher isoelectric point. PMID- 3338457 TI - Biosynthesis of monoterpene hydrocarbons by isolated chromoplasts from daffodil flowers. AB - Incubation studies using [1-14C]isopentenyl diphosphate and [1-2H2]isopentenyl diphosphate as substrates revealed that isolated chromoplasts from flowers of Narcissus pseudonarcissus L. are able to synthesize monoterpene hydrocarbons and linalool in high yields. The enzymes involved are soluble in the chromoplast stroma. It is hypothesized that in the plant cell plastids are the site of monoterpene biosynthesis, whereas the formation of sesquiterpenes may be restricted to the cytoplasm/endoplasmic reticulum. PMID- 3338458 TI - Ca2+ and Mg2+ as modulators of mitochondrial L-glycerol-3-phosphate dehydrogenase. AB - 1. Physiological concentrations of either Ca2+ or Mg2+ stimulated L-glycerol 3 phosphate oxidation by intact mitochondria isolated from various mammalian tissues (hamster brown adipose tissue, rat brain, liver of normal and hyperthyroid rats). A higher cation concentration was required for stimulation by Mg2+ than by Ca2+. L-glycerol-3-phosphate dehydrogenase was the target of the stimulation by both cations as revealed by measurements with intact mitochondria as well as with the solubilized enzyme. With different electron acceptors Ca2+ and Mg2+ stimulation occurred at significantly different cation concentrations. 2. Substrate activation of mitochondrial L-glycerol-3-phosphate dehydrogenase was observed in intact mitochondria and with the solubilized enzyme isolated from hyperthyroid rats in the absence of Ca2+ and Mg2+. According to kinetic analysis two independent binding sites, functioning with different turnovers and with different affinities for the substrate, could account for the phenomenon. In the presence of Ca2+ or Mg2+ substrate activation could not be detected; the kinetic parameters apparently correspond to the tight substrate-binding site functioning with high turnover. 3. Thiol group(s), which in the absence of Ca2+ and Mg2+ did not participate in the functioning of the enzyme, played an essential role in the binding of these cations to the enzyme, as shown by chemical modification studies. 4. From the solubilized mitochondrial proteins L-glycerol-3-phosphate dehydrogenase was bound selectively to the hydrophobic phenyl-Sepharose 4B matrix in the presence Ca2+, and the bound enzyme could be eluted with EDTA. This suggests that Ca2+ caused an alteration in the conformation of the enzyme. PMID- 3338459 TI - Elicitor-induced tyrosine decarboxylase in berberine-synthesizing suspension cultures of Thalictrum rugosum. AB - Tyrosine decarboxylase (EC 4.1.1.25) was induced in suspension cultures of Thalictrum rugosum by treatment with a yeast glucan elicitor. Maximum induction was observed at a carbohydrate concentration of 0.4 mg/g fresh weight of cells and maximum enzyme activity was reached 20 h after addition of elicitor. The enzyme was inducible in late exponential and early stationary growth phases. A good correlation between induced tyrosine decarboxylase activity and berberine biosynthesis has been established. It is suggested that tyrosine decarboxylase may be a key enzyme between primary and secondary metabolisms in the biosynthesis of norlaudanosoline-derived alkaloids. PMID- 3338460 TI - Identification and primary structure of the cardiolipin-binding domain of mitochondrial creatine kinase. AB - It was recently shown that the mitochondrial isozyme of heart creatine kinase binds to cardiolipin on the outer half of the inner membrane [Muller, M., et al. (1985) J. Biol. Chem. 260, 3839-3843]. The enzyme has now been extracted and purified to homogeneity from rat heart mitochondria, and cleaved with CNBr. The fragments have been separated on an FPLC system using a Mono Q HR 5/5 column. Only one of these binds to cardiolipin-containing liposomes and has thus been identified as the cardiolipin-binding domain of the enzyme. Its amino acid sequence has been determined. The fragment contains 25 amino acids and corresponds to the N-terminal region of the protein. The binding of the fragment of cardiolipin-containing liposomes was inhibited by adriamycin. Another and larger CNBr fragment could be specifically labelled with periodate-oxidized (di aldehyde) ATP and has thus been identified as the ATP-binding domain. Chemical modification of the basic amino acids Lys and Arg of the enzyme abolished its binding to cardiolipin. PMID- 3338461 TI - Inhibition of human glutathione reductase by the nitrosourea drugs 1,3-bis(2 chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1 nitrosourea. A crystallographic analysis. AB - Glutathione reductase from human erythrocytes was inhibited by incubation with the drugs 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-(2 hydroxyethyl)-1-nitrosourea (HeCNU) under quasi-physiological conditions. For reference purposes, iodoacetamide was used for inactivating alkylation of the enzyme. In each case the modified glutathione reductase was crystallized and its structure determined. These analyses showed that in all experiments the enzyme had reacted at the distal sulfur, that is at the thiol of Cys-58, and virtually nowhere else in the visible structure. The electron density of the HeCNU derivative at 0.3 nm resolution is consistent with a 2-hydroxyethyl group. This alkyl moiety has recently been identified by chemical analysis [Schirmer, R. H., Schollhammer, T., Eisenbrand, G. and Krauth-Siegel, R. L. (1987) Free Radical Res. Commun. 3, 3-12]. The 0.2 nm resolution electron-density map of the BCNU derivatized enzyme cannot be explained by a 2-hydroxyethyl group. Instead the modification appears as a carbamoyl moiety containing at least five non-hydrogen atoms. In this derivative the distal cysteine is forced into an unusual conformation. PMID- 3338462 TI - Purification and characterization of a liver microsomal cytochrome P-450 isoenzyme with a high affinity and metabolic capacity for coumarin from pyrazole treated D2 mice. AB - Microsomal coumarin 7-hydroxylase activity is regulated differently from several other monooxygenase enzymes, at least in mice [Wood, A. W. and Conney, A. H. (1974) Science (Wash. DC) 612-614]. Recently we found that in D2 mice this activity is strongly and selectivity induced by pyrazole [Juvonen, R. O., Kaipainen, P. K. and Lang, M. A. (1985) Eur. J. Biochem. 152-3-8]. This paper describes the purification of the pyrazole-inducible cytochrome P-450 isoenzyme. Because of the lability of the protein, a special procedure for the purification was developed. The procedure is based on a combination of hydrophobic and ion exchange chromatography and the presence of 100 microM coumarin in the preparations throughout the whole purification. Coumarin effectively protected the P-450 from degradation and also converted the pyrazole-inducible P-450 to its high-spin state. This enabled us to choose only those fractions for further purification where the P-450(s) was in its high-spin state (rather than measuring the content of the total P-450). As a result the purified protein had an apparent molecular mass of 49.7 kDa, a specific content of 19.9 nmol/mg protein and a very high affinity and metabolic capacity for coumarin. PMID- 3338463 TI - Penicillin-degrading activities of peptides from pneumococcal penicillin-binding proteins. AB - Trypsin treatment of native penicillin-binding proteins (PBPs) 1a, 2b and 3 from Streptococcus pneumoniae resulted in the formation of stable peptides containing the beta-lactam-binding site with molecular masses ranging from 26 kDa to 36 kDa. Whereas the PBP 1a peptide (Ia) was enzymatically rather unstable, the PBP 2b peptide (IIb) and the PBP 3 peptide (III) were able to bind and release beta lactams with similar rates compared to the intact PBP, the turnover rate of fragment II b was even twice as fast as that observed with PBP 2b. Analysis of the turnover products by thin-layer chromatography revealed that PBP 2b and 3 produced penicilloic acid as well as phenylacetylglycine. On the other hand, with the corresponding tryptic fragments only the hydrolysis product penicilloic acid was obtained. PMID- 3338464 TI - The hopanoids of the purple non-sulfur bacteria Rhodopseudomonas palustris and Rhodopseudomonas acidophila and the absolute configuration of bacteriohopanetetrol. AB - Five complex hopanoids have been detected in the purple non-sulfur bacterium Rhodopseudomonas acidophila. Next to the polyfunctionalized methylcyclopentane bacteriohopanetetrol ether already isolated from Methylobacterium organophilum, 35-carbamoylbacteriohopane-32,33,34-triol, 34,35-dicarbamoylbacteriohopane-32,33 diol and two nucleoside analogues, (22R)-30-(5'-adenosyl)hopane and (22S)-30-(5' adenosyl)hopane were isolated and identified by spectroscopic and chemical methods. In Rhodopseudomonas palustris, however, only 35-amino-bacteriohopane 32,33,34-triol was detected. Chemical correlation between adenosylhopane and bacteriohopanetetrol, as well as comparison of derivatives obtained from bacterial and synthetic hopanoids, permitted the determination of the configurations of all asymmetric centres of the side-chain of bacteriohopanetetrol as 22R, 32R, 33R and 34S. According to the stereochemistry, this side-chain could be a D-ribose derivative linked through its C-5 carbon atom to the hopane skeleton. PMID- 3338465 TI - Two different adenylyl cyclases in brain distinguished by monoclonal antibodies. AB - Four monoclonal antibodies, raised against the 115-kDa adenylyl cyclase from bovine brain [Pfeuffer, E. et al. (1985) EMBO J. 4, 3675-3679] have been selected and designated BBC-1 to BBC-4. BBC-1 and BBC-3 are highly specific for the 115 kDa enzyme from bovine brain. The two other antibodies, BBC-2 and BBC-4, recognize an additional 150-kDa adenylyl cyclase in bovine brain, but also in brain tissue from other species. In membranes from lung and myocardium (bovine and rabbit) only the 150-kDa species is detected by the crossreacting antibodies BBC-2 and BBC-4. The two adenylyl cyclases from brain can be separated by calmodulin-Sepharose: only the enzyme of 115 kDa but not that of 150 kDa was retained by the affinity resin and could be stimulated by Ca2+/calmodulin. The data obtained with these antibodies of defined specificity provide for the first time direct evidence for the presence of two distinct adenylyl cyclase species in brain tissue. PMID- 3338466 TI - Luteal progesterone synthesis and high-density lipoprotein. Evidence implicating a pronase-sensitive HDL-binding site in the mechanism by which HDL supports luteal progesterone synthesis. AB - We have shown previously that corpus luteum cells isolated from the superovulated ovaries of rats treated with 4-amino-pyrazolo[3,4-d]pyrimidine constitute a suitable experimental system by which to investigate the mechanism in which plasma high-density lipoprotein (HDL) plays a role in luteal cellular progesterone synthesis. In the present study, the rate of luteal cellular progesterone synthesis was shown to be stimulated by 125I-labelled HDL up to about 70% of the rate achieved in the presence of native HDL. The concentration of HDL needed for half-maximal stimulation of progesterone synthesis in the presence of lutropin was not significantly different irrespective of whether radioiodinated HDL or unlabelled HDL was used. Experimental conditions for studying the binding of 125I-labelled HDL to isolated luteal cells have been defined and cellular binding affinity and binding capacity have been measured. Exposure of the luteal cells to pronase virtually abolished their capacity to bind 125I-HDL and made them unable to respond to added HDL by increasing their rate of progesterone synthesis in the presence of lutropin. Control experiments showed this effect of pronase on cellular progesterone synthesis not to be due to destruction of cellular lutropin receptors, nor to general cellular damage. This evidence supports the view that luteal cellular binding of HDL is part of the mechanism by which HDL acts in luteal progesterone synthesis. Cellular binding capacity and affinity for 125I-labelled HDL were the same irrespective of whether or not lutropin was present during incubation. Furthermore, the binding capacity and affinity of cells from the ovaries of rats not treated with 4-amino pyrazolo[3,4-d]pyrimidine were the same as in luteal cells isolated from rats that had been treated. PMID- 3338467 TI - Structural and functional studies of the interaction of the eukaryotic elongation factor EF-2 with GTP and ribosomes. AB - The structure of the guanosine nucleotide binding site of EF-2 was studied by affinity labelling with the GTP analogue, oxidized GTP (oGTP), and by amino acid sequencing of polypeptides generated after partial degradation with trypsin and N chlorosuccinimide. Native EF-2 contains two exposed trypsin-sensitive cleavage sites. One site is at Arg66 with a second site at Lys571/Lys572. oGTP was covalently bound to the factor between Arg66 and Lys571. After further cleavage of this fragment with the tryptophan-specific cleavage reagent N chlorosuccinimide, oGTP was found associated with a polypeptide fragment originating from a cleavage at Trp261 and Trp343. The covalent oGTP . EF-2 complex was capable of forming a high-affinity complex with ribosomes, indicating that oGTP, in this respect, induced a conformation in EF-2 indistinguishable from that produced by GTP. Although GTP could be substituted by non-covalently linked oGTP in the factor and ribosome-dependent GTPase reaction, the factor was unable to utilize the covalently bound oGTP as a substrate. This indicates that the conformational flexibility in EF-2 required for the ribosomal activation of the GTPase was inhibited by the covalent attachment of the nucleotide to the factor. EF-2 cleaved at Arg66 were unable to form the high-affinity complex with ribosomes while retaining the ability to form the low-affinity complex and to hydrolyse GTP. The second cleavage at Lys571/Lys572 was accompanied by a total loss of both the low-affinity binding and the GTPase activity. PMID- 3338468 TI - Secondary structure and hydrogen bonding of crambin in solution. A two dimensional NMR study. AB - The secondary structure of crambin in solution has been determined using two dimensional NMR and is found to be essentially identical to that of the crystal structure. The H-D exchange of most amide protons can be accounted for in terms of the hydrogen bonds found in the X-ray structure. Exceptions are the amide protons of Cys-4 and Ser-6, which exchange more slowly than expected, and of Asn 46 for which the exchange is faster. These results might be explained by a slightly different conformation of the C-terminal region of the protein in solution. The slow exchange of the amides of Cys-32 and Glu-23 might be due to aggregation involving an extremely hydrophobic part of the protein in solution. PMID- 3338469 TI - An antibody to the low-density lipoprotein (LDL) receptor that partially inhibits the binding of LDL to cultured human fibroblasts. AB - A monoclonal antibody, raised initially against pure bovine low-density lipoprotein (LDL) receptor, was found to bind saturably to LDL receptors on the surface of cultured human fibroblasts. It was apparently internalized by the cells but rapidly returned to the surface and was not significantly degraded. LDL did not affect the binding of antibody. However, the antibody reduced both the apparent affinity of the receptor for LDL and the amount of LDL bound. In the presence of antibody, the concentration of LDL required for one-half maximum binding increased from 14.5 nM to 22.3 nM at 37 degrees C and from 2.8 nM to 11.5 nM at 4 degrees C. Maximum heparin-releasable binding of LDL was reduced by 56% at 37 degrees C and by 36% at 4 degrees C. Fab fragments halved the affinity at both temperatures without affecting the maximum amount of LDL bound. At 4 degrees C, maximum heparin-releasable LDL binding was the same as that of antibody and of Fab fragments. At 37 degrees C, heparin-releasable binding of LDL and binding of Fab fragments were double that at 4 degrees C, whereas binding of antibody remained unchanged. The results suggest that the antibody bound to a site on the receptor remote from the LDL binding region and that intact antibody recycled with the receptor. It halved LDL binding and degradation at 37 degrees C and reduced binding at 4 degrees C, probably through a different mechanism. The possibility that both cooling and antibody led to receptor aggregation is discussed. PMID- 3338470 TI - Purification and some properties of cathepsin B from rabbit skeletal muscle. AB - Cathepsin B was purified from rabbit skeletal muscle by ammonium sulfate fractionation and successive chromatographies on Sephadex G-75, phosphocellulose, peptide-conjugated Sepharose, DEAE-Toyopearl and Sephadex G-100. The purified enzyme gave a single protein band on SDS/polyacrylamide gel electrophoresis. The enzyme did not abolish the Ca sensitivity of the ATPase activity of myofibrils. The molecular mass of the enzyme was found to be 27 kDa on gel filtration and SDS/polyacrylamide gel electrophoresis. The optimum pH for the hydrolysis of N alpha-benzoyl-DL-arginine-beta-naphthylamide was 6.5. The enzyme was stable in the range of pH 4.5-5.5. Tetrathionate reacted with thiol groups of the enzyme reversibly so that it stabilized the enzyme. The enzyme was strongly inhibited by iodoacetate, HgCl2, antipain, leupeptin, N alpha-p-tosyl-L-lysine chloromethane and L-tosylphenylalanylchloromethane, but not by pepstatin or trypsin inhibitor. PMID- 3338471 TI - Characterization of an anti-thrombospondin monoclonal antibody (P8) that inhibits human blood platelet functions. Normal binding of P8 to thrombin-activated Glanzmann thrombasthenic platelets. AB - Stimulated human blood platelets release thrombospondin, an alpha-granule glycoprotein of 450 kDa. The aim of this work was to characterize an anti thrombospondin monoclonal antibody (P8) in order to study the role of thrombospondin in platelet functions. The presence of thrombospondin receptor sites on resting and thrombin-stimulated platelets of three Glanzmann's thrombasthenia patients and normal donors was investigated using the P8 monoclonal antibody. Monoclonal antibody P8 was extensively characterized using ELISA, immunoprecipitation, immunoadsorbent affinity chromatography combined with tryptic peptide map analysis and crossed immunoelectrophoretic techniques. Labelled P8 bound strongly to thrombin-stimulated normal platelets (n = 14917 +/- 420, mean +/- SD) (Kd = 9.2 +/- 3.0 nM) and poorly to resting platelets (n = 2697 +/- 1278) (Kd = 24.8 +/- 18.6 nM). Moreover, the number of binding sites for P8 on thrombin-stimulated platelets from three Glanzmann's thrombasthenia patients, lacking the IIb-IIIa glycoprotein complex, were found similar to normal samples. F(ab')2 fragments of P8 inhibited aggregation of, and reduced secretion from, washed platelets stimulated by low concentrations of thrombin (0.05-0.06 U/ml) and collagen (0.5-0.6 microgram/ml). F(ab')2 fragments of P8 inhibited thrombin induced platelet aggregation, but did not reduce fibrinogen binding (n) nor affect its dissociation constant (Kd). Inhibition of platelet aggregation by P8 suggests that thrombospondin plays an active role in promoting platelet aggregation, at low concentrations of thrombin and collagen. Normal binding of P8 to thrombin-stimulated Glanzmann thrombasthenic platelets indicates the presence of a thrombospondin receptor on the platelet surface distinct from the GPIIb-IIIa complex. PMID- 3338473 TI - Cytochrome b6f complex is required for phosphorylation of light-harvesting chlorophyll a/b complex II in chloroplast photosynthetic membranes. AB - The light-harvesting chlorophyll a/b complex (LHC II) and four photosystem II (PS II) core proteins (8.3, 32, 34 and 44 kDa) become phosphorylated in response to reduction of the intersystem electron transport chain of green plant chloroplasts. Previous studies indicated that reduction of the plastoquinone (PQ) pool is the key event in kinase activation. However, we show here that, unlike PS II proteins, LHC II is phosphorylated only when the cytochrome b6f complex is active. Two lines of evidence support this conclusion. (1) 2,5-Dibromo-3-methyl-6 isopropyl-p-benzoquinone (DBMIB) and the 2,4-dinitrophenyl ether of iodonitrothymol (DNP-INT), which are known to block electron flow into the cytochrome complex, selectively inhibit LHC II phosphorylation in spinach thylakoids. (2) The hcf6 mutant of maize, which contains PQ but lacks the cytochrome b6f complex, phosphorylates the four PS II proteins but fails to phosphorylate LHC II in vivo or in vitro. PMID- 3338472 TI - Purification and characterization of a bacterial dehalogenase with activity toward halogenated alkanes, alcohols and ethers. AB - An enzyme that is capable of hydrolytic conversion of halogenated aliphatic hydrocarbons to their corresponding alcohols was purified from a 1,6 dichlorohexane-degrading bacterium. The dehalogenase was found to be a monomeric protein of relative molecular mass 28,000. The affinity for its substrates was relatively low with Km values for short-chain haloalkanes in the range 0.1-0.9 mM. The aliphatic dehalogenase showed a much broader substrate range than has been reported for halidohydrolases so far. Novel classes of substrates include dihalomethanes, C5-C9 1-halo-n-alkanes, secondary alkylhalides, halogenated alcohols and chlorinated ethers. Several of these compounds are important environmental pollutants, e.g. methylbromide, dibromomethane, 1,2-dibromoethane, 1,3-dichloropropene, and bis(2-chloroethyl)ether. The degradation of chiral 2 bromoalkanes appeared to proceed without stereochemical preference. Optically active 2-bromobutane was converted with inversion of configuration at the chiral carbon atom, suggesting that the dehalogenase reaction proceeds by a nucleophilic substitution involving a carboxyl group or base catalysis. PMID- 3338474 TI - Defective biopterin synthesis and birth weight. PMID- 3338475 TI - Alterations of intracranial pressure and cerebral blood flow velocity in healthy neonates and their implication in the origin of perinatal brain damage. AB - Intracranial pressure and cerebral blood flow velocity were recorded in term healthy neonates during the first 3 days of life using non-invasive methods (LADD fontanometry and cw-Doppler sonography). Intracranial pressure increased from 4.0 +/- 2.7 cm H2O to 5.8 +/- 2.7 cm H2O and maximal cerebral blood flow velocity in the anterior cerebral artery (ACA) increased from 33 cm/s to 58 cm/s as calculated from a Doppler shift of 0.63 to 1.10 kHz and vascular resistance decreased between the 1st and 3rd day of life. These alterations could not be demonstrated in the femoral artery. This is in accordance with other registrations obtained by different methods and under various conditions. They allow an explanation of some well known physiological phenomena like alterations of cranial volume and the structure of the bony skull in the first days of life. Furthermore, these physiological variations may have implications for the origin of cerebral damage during the perinatal period, especially of hypoxic-ischaemic encephalopathies. PMID- 3338476 TI - Clostridium difficile in neonates: serogrouping and epidemiology. AB - A typing scheme for Clostridium difficile based on serogrouping, toxigenicity and sorbitol fermentation was applied to 270 strains isolated in one neonatal ward during a 6-month prospective study. Two hundred and twenty-three strains were isolated from 377 faecal samples of 114 neonates and 47 from 92 environmental specimens. The isolates were distributed among five different types; 87% of the faecal and 85% of the environmental isolates belonged to two of these types (toxigenic, sorbitol negative, serogroup F and nontoxigenic, sorbitol positive, serogroup A). Nosocomial spread was clearly demonstrated and the environment appeared to be the main source of contamination: most of the neonates were colonized after admission by strains found in their environment; clusters of colonization with unusual isolates were observed following referral of patients from the intensive care unit or from other hospitals. No relation was found between the acquisition or the carriage of C. difficile and any intestinal symptoms. All the strains belonged to types different from those usually found in cases of antibiotic associated colitis (AAC) suggesting differences of pathogenicity among the different types. PMID- 3338477 TI - Reflex sympathetic dystrophy: an underreported syndrome in children? AB - Two cases of reflex sympathetic dystrophy are described in a 13-year-old and a 10 year-old girl. In the latter, symptoms occurred consecutively in the right leg, the left foot and the left hand. In contrast to the usual findings in adults, bone scintigraphy showed decreased radio-isotope uptake in the affected area during the early phase. An electromyography performed in the younger patient showed slower nerve conduction velocity in the affected limb. The younger girl improved following physical therapy and calcitonin injections, while the older patient favorably responded to sympathetic blockade. PMID- 3338478 TI - Thrombocytopenia: a complication of Kawasaki disease. AB - Thrombocytopenia was observed in 10 (2.0%) of 486 children with Kawasaki disease. In nine of the ten, the minimal platelet count of 94,000 +/- 38,000 (SD)/mm3 was seen on day 6.8 +/- 2.2 (SD) of illness and the platelet counts were elevated to the normal level in 1-2 weeks. Thrombocytopenia in the nine appeared to be caused via coagulation-mediated platelet consumption, while the remaining child was diagnosed as having idiopathic thrombocytopenic purpura. One of the two who had severe coagulation-mediated thrombocytopenia of less than 50,000/mm3 developed coronary aneurysms persisting over 1 year. PMID- 3338479 TI - Oestrogen treatment of constitutionally tall girls with 0.1 mg/day ethinyl oestradiol. AB - For the treatment of tall stature in girls, oestrogens are usually given in high doses. In this study, growth data of 35 constitutionally tall girls treated with only 0.1 mg/day ethinyl oestradiol (EE) are reported (Group 1). The data were compared with those of 23 untreated girls with comparable bone ages and growth potential (Group 2), and with those of 5 girls treated with 0.3 mg/day EE (Group 3). All groups were followed until cessation of growth. In group 1, the median bone age at the onset of treatment was 12.50 years (Greulich-Pyle, range 10.50 13.75), and the median height prediction was calculated to be 184.4 cm (Bayley Pinneau, range 179.5-191.5). Following oestrogen treatment of 21 months duration (range 10-37) the median adult height was reduced by 4.3 cm (range 0.0-9.0), or 3.9 cm if corrected for the error of prediction in the control group. The effect was greater in those girls with bone ages below 12.5 years at the onset of treatment (6.7 cm/corrected value 7.4 cm) than in the older girls (4.2 cm/3.6 cm). In Group 2 (controls) the median final adult height was over-estimated by 0.4 cm (range-4.9 to 4.9), but was under-estimated by 0.7 cm in those girls with bone ages below 12.5 years. In girls of comparable bone age similar reductions were obtained whether 0.3 mg/day EE (Group 3) or 0.1 mg/day was given (4.4 vs. 4.2 cm). A comparison of these results with published data indicates that higher EE doses (0.3-0.5 mg/day) have only little, if any, greater effect on the growth of girls than the dosage of 0.1 mg/day EE used in this study. PMID- 3338480 TI - Plasma fibronectin concentrations in healthy newborns and in children. AB - Plasma fibronectin (FN) concentrations were measured by an immunonephelometric method in cord blood from 76 healthy newborns (45 full term and 31 preterm), in 181 healthy children, from 1 month-15 years old, divided by age into seven groups and in 81 control adults. FN levels in newborns were 35% of those of adults. There was no difference between plasma FN in term and preterm (gestational age greater than 30 weeks) infants. Preterm newborns below the gestational age of 30 weeks showed particularly low FN levels. No clear correlation was seen with birth weight. In the child population, a strong increase in FN values was noted in the first 6 months of life, rising to 65% of the normal adult values. No further increase occurred until puberty. PMID- 3338481 TI - Blood lead and erythrocyte zinc protoporphyrin in mothers and newborn infants. AB - Blood lead (B-Pb) and erythrocyte zinc protoporphyrin (ZPP) were measured in 78 mothers at delivery and in cord blood from 48 infants living in an area with low atmospheric Pb pollution. Median B-Pb was 35 micrograms/l (range 6-63) in mothers and 20 micrograms/l (range 6-50) in infants (P less than 0.0001), and the values were significantly correlated (rs = 0.73, P less than 0.0001). Mean B-Pb infant/B Pb mother ratio was 0.7 (range 0.2-1.4). Mothers had lower ZPP (median 1.6 microgram/g Hb) than infants (median 2.9) (P less than 0.0001). ZPP in mothers showed a stronger relation to iron status (serum transferrin, serum ferritin) than to B-Pb (rs = 0.22, P less than 0.05). B-Pb was correlated to serum iron both in mothers (rs = 0.28, P less than 0.02) and infants (rs = 0.33, P less than 0.03). The present B-Pb levels are lower than previously reported in Scandinavia, probably due to the general decline in atmospheric Pb pollution. PMID- 3338482 TI - Sinus tachycardia in term infants preceding sudden infant death. AB - The quantities of sinus tachycardia in 24-h recordings of the electrocardiogram from 16 full-term infants (greater than or equal to 37 weeks gestation) who were subsequently victims of the sudden infant death syndrome (SIDS), from 230 randomly selected age-matched full-term survivors and from 64 full-term survivors matched for age and birth weight were measured by computer and manual analysis techniques. Of 16 infants dying of SIDS, 7 had elevated levels of sinus tachycardia (greater than 95th centile in controls) (P less than 0.01). Although high levels of sinus tachycardia might be of value in identifying infants at high risk of SIDS, these encouraging findings must first be validated by further prospective studies. PMID- 3338484 TI - The cot in cot deaths. AB - Little attention is paid to the cot in cot deaths. We report two cases of cot deaths which occurred in practically identical circumstances, with the infants lying face downwards in soft woven-type carrying baskets. The infants were probably unable to turn their heads to one side to maintain ventilation, due to the construction of these soft baskets with soft mattresses. This probably played an important role in the deaths. PMID- 3338483 TI - Lead and sudden infant death. Investigations on blood samples of SID babies. AB - To investigate a potential relationship between an elevated lead burden and sudden infant death (SID), the lead concentrations (Pb-B) were determined in 41 blood samples from SID babies and compared with the Pb-B of 5 babies who died traumatically and 77 living control babies. Several factors that may influence the Pb-B were taken into consideration, especially a dependence of the Pb-B on age and social class. Moreover, a post-mortem water shift occurs in the blood. Even taking these factors into consideration the distribution of the Pb-B's of the SID group was found to differ on a highly significant level (greater than 99.9%) from the control group. Five Pb-B's of the SID group were higher than the highest lead concentration found in blood from the control babies. Negative influences of lead on the pre- and postnatal maturation of the brain are discussed in the search for a possible causal connection between an elevated lead burden and the occurrence of SID. PMID- 3338486 TI - An asymmetric bulging of the chest as a leading sign of a cardiac fibroma in a child. AB - A 17-month-old child with an asymmetrical bulging of the chest due to an intramural fibroma of the heart is described. The clinical symptoms that may be caused by cardiac tumours are discussed. To detect these tumours several investigations can be performed, of which echocardiography is the most specific. Surgical resection of these tumours should be attempted, even if a complete resection is not possible. PMID- 3338487 TI - Proceeings of the 4th EOTRC Breast Cancer Working Conference. London, 1-3 July 1987. PMID- 3338485 TI - Methaemoglobinaemia in young infants with diarrhoea. AB - Seventeen infants under 2 months of age are described who presented with methaemoglobinaemia and acute diarrhoea during a period of 2 years. No infants beyond this age presented with such characteristics. In none of them was one of the known mechanisms of methaemoglobin formation found. All infants recovered with conventional therapy. Methaemoglobin associated with diarrhoea relapsed in three infants before they were 2 months old. Twenty-six similar cases have been reported in the literature. The mechanism of methaemoglobinaemia in these infants is unclear. PMID- 3338488 TI - Epidemiology and prevention: workshop report. PMID- 3338489 TI - Imaging techniques in breast cancer: workshop report. PMID- 3338490 TI - Management of early stage breast cancer--current status of treatment: workshop report. PMID- 3338491 TI - Cell kinetics, growth rate and the natural history of breast cancer. The Heuson Memorial Lecture. PMID- 3338492 TI - Thrombospondin binding by human squamous carcinoma and melanoma cells: relationship to biological activity. AB - Human squamous carcinoma cells attach and spread on thrombospondin (TSP)-coated culture dishes but exhibit significant variability among individual cell lines in their degree of responsiveness. Using a highly responsive squamous carcinoma line and a cell line which is much less responsive (as well as a human melanoma cell line which does not respond at all in the adhesion assay), we have examined binding of exogenous radiolabeled TSP. The cells which were the most responsive to TSP in the adhesion assay bound the greatest amount of radiolabeled ligand. Binding was time- and dose-dependent, saturable, inhibitable with excess unlabeled TSP, reversible, and specific. The less-responsive squamous carcinoma cells bound only 25-30% of the amount of TSP bound by the highly responsive cells while the nonresponsive melanoma cells bound less than 10% of the amount bound by the highly responsive squamous carcinoma cells. Our previous studies (J. Varani et al. (1986) Exp. Cell Res. 167, 376) have shown that the highly responsive squamous carcinoma cells also synthesized the greatest amount of TSP as indicated by biosynthetic labeling studies. The less-responsive squamous carcinoma cells were intermediate in synthetic activity and no synthetic activity was seen with the melanoma cells. These findings suggest that the amount of ligand bound may determine the degree of biological responsiveness and that endogenously synthesized TSP may be the source of that ligand. PMID- 3338493 TI - The influence of the genotype on the process of ageing of chick lens cells in vitro. AB - We reported previously that changes in crystallin expression in differentiating long-term primary cultures of lens cells from five different chick genotypes are similar to those which occur in vivo between hatching and the 8-week-old adult. These changes followed a similar program in all genotypes but occurred more rapidly in cells from the fast-growing than from the slow-growing genotypes. The present study examines ageing changes in lens cell populations from the same five genotypes, over a 4-6 month period, using long-term serial subcultures. The capacity for lentoid differentiation was progressively lost, but the rate of loss was inversely related to the intrinsic growth rate of the cells of these genotypes, occurring at the first passage in the slowest-growing strain, while fifth passage cells of the fastest-growing strain still retained some lentoid forming capacity. The rate of loss of crystallin expression was also inversely related to the genetic growth rate, but the sequence of changes appears to be nonrandom, since it was broadly similar in all genotypes, starting with a preferential loss of delta-crystallin, as occurs in vivo; although alpha- and beta-crystallins were undetectable in late dedifferentiated cultures, the capacity of the cells for their synthesis was still present. Cultures from both fast-growing genotypes eventually showed senescence, but those from all three slow-growing genotypes underwent transformation. The major cell component in late cultures of all genotypes was actin. PMID- 3338495 TI - Differences in growth factor sensitivity between individual 3T3 cells arise at high frequency: possible relevance to cell senescence. AB - At low serum concentrations (3% or less), individual Swiss 3T3 cells display marked heterogeneity in proliferative capacity. Here we show that this heterogeneity arises at extremely high frequency within a clone, often with sister cells showing considerable differences in capacity for further proliferation. The heterogeneity is unlikely to be due to genetic instability or mutation. Instead, it appears to reflect physiological differences between cells in their requirement for serum growth factors. It is suggested that these differences arise because cells are unable to sustain production, at low growth factor concentrations, of some rare component which is itself required for growth factor action. We believe that the generation of heterogeneity in 3T3 cells has much in common with the phenomenon of senescence in diploid cells. PMID- 3338494 TI - The timing of initiation of DNA synthesis in Paramecium tetraurelia is established during the preceding cell cycle as cells become committed to cell division. AB - The timing of initiation of DNA synthesis (IDS) in Paramecium is established before cell division at a point located at about 0.75 in the preceding cell cycle. This point occurs about 90 min prior to fission and coincides with the point at which cells become committed to cell division. The location of the point at which the timing of IDS is set was deduced from a series of nutrient-shift experiments. Changes in nutrient level lead to changes in the duration of the subsequent G1 interval when they occur more than 90 min prior to fission. Perturbation of the cell cycle so that the timing of commitment to cell division is altered, results in a parallel shift in the point at which the timing of IDS is established. PMID- 3338496 TI - Enhancement of cytotoxicity of modeccin by nigericin in modeccin-resistant mutant cell lines. AB - We have isolated a Chinese hamster ovary cell mutant (DMPR-2) simultaneously resistant to diphtheria toxin and modeccin. In addition to the increased resistance to these two toxins used in the selection, this mutant is more resistant to Pseudomonas toxin and hypersensitive to ricin than the parental cell line. In contrast to the wild-type cells in which nigericin protects cells from modeccin, the cytotoxicity of modeccin in the DMPR-2 mutant is enhanced by nigericin. We have also studied the effects of nigericin and NH4Cl on the cytotoxicity of modeccin in a modeccin-resistant mutant of HeLa cells (ModRI). The cytotoxicity of modeccin is enhanced by nigericin in ModRI mutant cells, in contrast to the protection of modeccin cytotoxicity by nigericin in the parental HeLa cells. Our results suggest that modeccin can reach the cytosol of mammalian cells by two distinct routes; the major route requires endosomal acidification and the minor route is activated by nigericin. PMID- 3338497 TI - Effect of monensin on receptor recycling during continuous endocytosis of asialoorosomucoid. AB - The binding of asialoglycoproteins to their liver cell receptor results in internalization of the ligand-receptor complex. These complexes rapidly appear in intracellular compartments termed endosomes whose acidification results in ligand receptor dissociation. Ligand and receptor subsequently segregate: ligand is transported to lysosomes and is degraded while receptor recycles to the cell surface. The proton ionophore monensin prevents acidification of endosomes and reversibly inhibits this acid-dependent dissociation of ligand from receptor. The present study determined the effect of monensin treatment of short-term cultured rat hepatocytes on cell-surface-receptor content, determined both by their binding activity and immunologically, following continuous endocytosis of asialoorosomucoid. Inclusion of 5 microM monensin in the incubation medium reduced the number of immunologically detectable cell-surface receptors by 20% in the absence of ligand. During continuous endocytosis of asialoorosomucoid, inclusion of monensin resulted in a 30-40% reduction of cell-surface receptor detectable either by ligand binding or immunologically. These results suggest that the reduced liver-cell-surface content of receptor in monensin is due to intracellular trapping of ligand-receptor complexes. The reduction of surface receptor during monensin incubation in the absence of ligand suggests that "constitutive recycling" of plasma membrane components also requires intracellular acidification. PMID- 3338498 TI - Effects of cis-4-hydroxy-L-proline, and inhibitor of Schwann cell differentiation, on the secretion of collagenous and noncollagenous proteins by Schwann cells. AB - The proline analog cis-4-hydroxy-L-proline (CHP) was previously shown to inhibit both Schwann cell (SC) differentiation and extracellular matrix (ECM) formation in cultures of rat SCs and dorsal root ganglion neurons. We confirmed that CHP inhibits basal lamina formation by immunofluorescence with antibodies to laminin, type IV collagen, and heparan sulfate proteoglycan. In order to test the hypothesis that CHP inhibits SC differentiation by specifically inhibiting the secretion of collagen, cultures grown in the presence or absence of CHP were metabolically labeled with [3H]leucine and the media were analyzed for relative amounts of (a) collagenous and noncollagenous proteins by assay with bacterial collagenase and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE), or (b) triple-helical collagen by pepsin digestion followed by SDS-PAGE. The results indicate that although CHP inhibited the accumulation of secreted collagen in the culture medium and disrupted collagen triple-helix formation, it also significantly inhibited the accumulation of secreted noncollagenous proteins in the medium. CHP had no significant effect on either total protein synthesis (medium plus cell layer) or cell number. We conclude that CHP does not act as a specific inhibitor of collagen secretion in this system, and thus data from these experiments cannot be used to relate SC collagen production to other aspects of SC differentiation. We discuss the evidence for and against specificity of CHP action in other systems. PMID- 3338499 TI - Reduction in DNA repair capacity following differentiation of murine proadipocytes. AB - It has been suggested that terminally differentiated mammalian cells have a decreased DNA repair capacity, compared with proliferating stem cells. To investigate this hypothesis, we have examined gamma-ray-induced DNA strand breaks and their repair in the murine proadipocyte stem cell line 3T3-T. By exposure to human plasma, 3T3-T cells can be induced to undergo nonterminal and then terminal differentiation. DNA strand breaks were evaluated using the technique of alkaline elution. No difference was detected among stem, nonterminally differentiated, and terminally differentiated cells in the initial levels of radiation-induced DNA strand breaks. Each of the strand break dose response increased as a linear function of gamma-ray dose. The strand breaks induced by 4 Gy rejoined following biphasic kinetics for each cell type. At each time point examined after irradiation, however, the percentage of strand breaks that had not rejoined in terminally differentiated cells was three to six times greater than in stem cells. The rate of strand break rejoining in nonterminally differentiated cells was of an intermediate value between that of the stem and of the terminally differentiated cells. These results indicate that, at least for 3T3-T cells, differentiated cells have a reduced capacity for DNA repair. PMID- 3338500 TI - Measles in developing countries. Part I. Epidemiological parameters and patterns. AB - This paper presents a review of published data concerning the epidemiology of measles in developing countries. Simple mathematical models provide a framework for data analysis and interpretation. The analyses highlight differences and similarities in the patterns of transmission of the measles virus in developed and developing countries. Whilst the rate of loss of maternally derived immunity to measles is broadly similar, the average age at infection is much lower, and case fatality rates are much higher in developing countries. Data analysis also serves to illustrate inter-relationships between different kinds of epidemiological data. Thus, for example, in order to correctly interpret an age stratified serological profile from a developing country it is necessary to have information on the rate of decay of maternal antibodies and age specific case fatality rates. To determine the probable impact of a given vaccination programme, information on the birth rate in the community concerned is also required. A discussion is given of the epidemiological data required in order to effectively design a community based vaccination programme aimed at the eradication of measles. PMID- 3338501 TI - Hepatitis B markers in Lancashire police officers. AB - A total of 284 Lancashire police officers each with a minimum of 5 years experience was tested for evidence of hepatitis B infection. None was hepatitis B surface antigen positive (HBsAg). Three were positive for both antibody to hepatitis B core antigen (anti-HBc) and HBsAg (anti-HBs). Five were positive for anti-HBc alone. Thus the overall prevalence was 2.8% which is within the range reported for blood donors in the UK. There was no association with working in the drug squad or custody office but there was a higher prevalence in those who had worked in the scene-of-crime's squad. However, the numbers were small, and of this group of 28 officers, 2 of the 3 with detectable hepatitis B markers were positive for anti-HBc alone. Therefore for police officers in mixed rural/urban areas of the UK, routine administration of hepatitis B vaccine is not justified although special consideration should be given to those working in selected groups. Further studies are required to ascertain whether there may be an increased risk for police officers working in conurbations. PMID- 3338502 TI - Routine surveillance data on AIDS and HIV infections in the UK: a description of the data available and their use for short-term planning. AB - In the UK surveillance of AIDS and HIV infection is based on routine reporting systems. Whilst attempts are made to ensure that AIDS data are as complete as possible, numbers of reports fluctuate from month to month for reasons which are described. In 1986 there was an increase in death certificates naming AIDS as a cause of death in patients who were not identifiable in the surveillance data. More active surveillance is now undertaken in order to minimize this and other possible discrepancies. It is probable that most cases of AIDS are reported and therefore these data can be used to describe trends in the epidemic by 'risk group'. Laboratory reports of HIV antibody-positive tests could give an earlier indication of trends because of the long incubation period of AIDS. But these laboratory data are difficult to interpret because they represent an incomplete and biased sample of all positive persons. AIDS cases are still being reported at a rate which is increasing approximately exponentially. Short-term predictions are presented showing a growth in the epidemic which is consistent with previously published predictions. Most cases are in the homosexual risk group. New asymptomatic homosexual patients with HIV antibody are still being identified. The epidemic of AIDS in haemophilia patients should be of finite size although new cases of AIDS are likely to continue to be diagnosed for several years. AIDS due to blood transfusion given in the UK before donor screening appears to be a much smaller epidemic. The epidemic in drug abusers is increasing. Heterosexually acquired AIDS and HIV infections are being reported in small but increasing numbers. PMID- 3338503 TI - The extent of surface contamination of retailed chickens with Campylobacter jejuni serogroups. AB - Eighty-two chickens purchased at 11 retailers (supplied by 12 wholesalers) in the south of England were cultured for Campylobacter jejuni by a method involving total immersion. The organism was isolated from 22 (48%) of 46 fresh birds, 12 of 12 uneviscerated (New York dressed) birds, but only 1 of 24 frozen birds. Viable counts of up to 1.5 x 10(6)/chicken were obtained from fresh birds and 2.4 x 10(7)/chicken from uneviscerated birds. Surface swabbing of breasts, thighs, wings and vents of fresh chickens showed that contamination was generally distributed over the carcasses. Salmonellas were found in only 2 of 69 of the fresh chickens. The prevalence of several Lior and Penner C. jejuni serogroups was similar in chickens and sporadic human cases of enteritis. Penner serogroup 4 (mostly of Lior serogroup 1) was found in 26% of human isolates and 14% of chicken isolates. The rising incidence of campylobacter enteritis during the last 6 years could well be a reflection of the increasing proportion of fresh chickens consumed over that period (32% higher in 1986 than in 1981). PMID- 3338505 TI - Costing of a hospital-based outbreak of poultry-borne salmonellosis. AB - Poultry-borne salmonellosis is the most common form of foodborne infection in Scotland for which the vehicle can be identified, yet little is known about the costs imposed on society by this disease, or the costs of preventing it. The present study identifies and values the costs of a hospital based outbreak of poultry-borne salmonellosis. Account is taken of costs falling on individuals, the health services and society as a whole. Depending on assumptions made about the value of 'intangibles', the cost of the outbreak is estimated to be between pounds 200,000 and pounds 900,000. PMID- 3338506 TI - The vertical transmission of salmonellas and formic acid treatment of chicken feed. A possible strategy for control. AB - The treatment of feed given to laying hens with 0.5% formic acid reduced significantly the isolation rate of salmonellas and was associated with a reduction in the incidence of infection in newly hatched chicks. These improvements were not sustained until slaughter, however, as growing birds acquired salmonellas, probably from feed which was not acid treated. The data indicate that formic acid treatment of chicken food could have important benefits for the public health. PMID- 3338504 TI - Experimental colonization of broiler chicks with Campylobacter jejuni. AB - Minimal colonization inocula for two broiler strains of Campylobacter jejuni were determined in broiler chicks aged 2-3 days and 2 weeks. Individually housed chicks were exposed to a single oral or cloacal challenge. Diarrhoeal symptoms were absent in all 380 chicks included in the study. Chick susceptibility to the two C. jejuni strains varied. Colonization was effected by less than 10(2)-10(4) colony forming units (c.f.u.) via cloacal challenge and 10(4)-10(6) c.f.u. via the oral route. Colonization inocula for 2- to 3-day and 2-week-old chicks were similar. Treatment of 1-day-old chicks with fresh adult caecal flora or an anaerobic broth culture of adult caecal flora did not inhibit colonization after challenge with low-dose C. jejuni. Susceptible chicks were colonized rapidly. C. jejuni was detected in 167 of 189 (88%) colonized chicks within 3 days of challenge and persisted during the 2-week monitoring period. Our data suggest that colonization of broiler chicks with C. jejuni is effected more easily by the cloacal than the oral route and is independent of age. PMID- 3338507 TI - Occurrence of multiple antibiotic resistance and R plasmids in Enterobacteriaceae isolated from children in the Sudan. AB - The prevalence of resistance to six commonly-used antimicrobial agents in faecal coliforms from children in Khartoum, Sudan was studied. A relatively high prevalence of resistance was found, ranging from 96% of children with isolates resistant to ampicillin to 70% of children with isolates resistant to chloramphenicol. Seventy-seven percent of children had isolates with high-level resistance to trimethoprim (MIC greater than 1000 micrograms/ml). Twenty-nine different resistance patterns were found. Thirty-nine percent of the children had isolates resistant to all six antibiotics studied, and 80% of children had isolates resistant to at least four. Transfer of resistance to each of the antimicrobials, in varying combinations, was demonstrated, but did not occur for all resistance patterns. Plasmid analysis showed plasmids ranging from 160 MDa to 2.8 MDa and isolates contained from one to five plasmids of different sizes. There were no consistent relationships between resistance pattern and plasmid profile, but multiple resistance transfer was mediated commonly by plasmids with a molecular weight of 62 MDa. The high prevalence of potentially transferable antibiotic resistance in gut commensals of children in the Sudan may be of importance in the management of enteric and other infections requiring antimicrobial treatment. PMID- 3338508 TI - The cause of anemia in mutant mice of Sl/Slt genotype: hypoplasia in bone marrow and restricted hyperplasia in spleen. AB - The cause of the severe anemia in Sl/Sld mice is attributed to (1) hypoproduction of erythrocytes due to a defect in the erythropoietic microenvironment and (2) bleeding from stomach ulcers. Sl/Slt mice also showed a moderate anemia, but bleeding from stomach ulcers was excluded as a cause of the anemia, because no significant amount of radioactivity was excreted in feces after the injection of 59Fe-labeled erythrocytes. The activity of erythropoiesis in the bone marrow and spleen was compared between Sl/Slt and congenic +/+ mice using three different criteria: the number of erythroblasts, 59Fe incorporation, and the number of erythropoietic precursor cells. All three parameters in the femur were lower, and those in the spleen were higher in Sl/Slt mice than in +/+ mice, suggesting that the low erythropoietic potential in the bone marrow of Sl/Slt mice is partially compensated by the spleen. In fact, splenectomy aggravated the anemia of Sl/Slt mice. The enhanced erythropoiesis in Sl/Slt spleens may explain our previous finding that numbers and sizes of spleen colonies were normal when bone marrow cells were injected into irradiated Sl/Slt mice. Sl/Slt mice may be a useful model for studying biological characteristics of the hematopoietic microenvironment. PMID- 3338509 TI - Proliferation and differentiation of human erythropoiesis in vitro: effect of different human lipoprotein species. AB - In order to permit erythroid proliferation in agar, a serum-free system was developed based on McCoy's 5A medium at pH 8.0, containing deionized and delipidated bovine serum albumin, iron-saturated transferrin, and crude erythropoietin (step III). Addition of the entire complement of serum lipoproteins, termed lipoprotein fraction I (density, less than 1.21 g/ml), increased the number of erythroid colony-forming units and erythroid burst forming units to numbers indistinguishable from those observed with media containing serum. Moreover, terminal differentiation occurred to fully hemoglobinized normoblasts and even mature erythrocytes. Under these conditions, the erythropoietin dose-response curve obtained when not using serum was comparable to that with serum. Colony formation also displayed a linear relationship to seeding densities down to limiting dilutions. For differential analysis of the main density lipoprotein fractions, sequential ultracentrifugation was performed to isolate very low-density lipoproteins, low density lipoproteins (LDL), high-density lipoproteins2 (HDL2), and HDL3, which were then added individually to serum-free cultures. Of the main lipoprotein classes, LDL exhibited the most proliferative capacity, followed by HDL2 and HDL3. Our findings indicate that when serum is substituted by well defined compounds including highly purified lipoprotein fractions, a serum-like proliferation and differentiation of human erythropoietic progenitor cells in agar can be obtained. PMID- 3338510 TI - Increase in circulating megakaryocyte growth-promoting activity (Meg-GPA) following sublethal irradiation is not related to decreased platelets. AB - In this study, we have used the sublethally irradiated rat as a model to examine the relationship between platelet count and the plasma level of megakaryocyte growth-promoting activity (Meg-GPA) assayed in vitro. Meg-GPA of irradiated rats whose platelet counts were maintained by platelet transfusions was compared to that of irradiated controls allowed to develop thrombocytopenia. The irradiated controls were given either saline, packed red cells, or no other treatment. Blood values were determined and plasma was collected from all groups 11 days after irradiation, predetermined to be the nadir of platelet count and the peak of Meg GPA. The Meg-GPA of plasma was assayed by culturing in vitro at a final concentration of 30% with rat marrow in methylcellulose and 2-mercaptoethanol for 7 days at 37 degrees C. Plasma from platelet-transfused irradiated rats, when collected at ambient temperature, contained markedly decreased levels of Meg-GPA compared to that present in plasma of irradiated controls. Subsequent in vitro studies indicated that elevated Meg-GPA levels of plasma from irradiated thrombocytopenic rats were drastically reduced by incubation with platelets in vitro at 37 degrees C. Incubation of the same plasma with platelets at 4 degrees C resulted in much less reduction in Meg-GPA. This suggested that the diminished Meg-GPA observed with plasma from the platelet-transfused irradiated rats may have been due to activation and release of Meg-GPA inhibitors from platelets during plasma collection. To investigate this possibility, experiments were repeated in which platelets of irradiated rats were maintained by platelet transfusion, but plasma was collected at 4 degrees C. Under these conditions, the level of Meg-GPA in plasma of the platelet-transfused irradiated rats was not markedly different from that in plasma of irradiated controls. We conclude that in this experimental model, circulating Meg-GPA level is not related to platelet count. PMID- 3338511 TI - Kinetics of myeloid progenitor cells in human micro long-term bone marrow cultures. AB - Hemopoiesis was analyzed in a miniaturized long-term culture of human bone marrow cells by quantifying the production of granulocyte-macrophage progenitor cells. As in the conventional long-term culture system, hemopoiesis was dependent on the presence of a marrow-derived adherent layer. Adipocytes proved to be essential for long-term proliferation. Optimal growth conditions were maintained by incubation in McCoy's medium supplemented with hydrocortisone, fetal calf serum, and horse serum. When calculated back to the volume of conventional cultures, the numbers and kinetics of nucleated cells and granulocyte-macrophage colony-forming cells were comparable in both culture systems. The microsystem is therefore suitable for performing multiple analyses on small samples of cells. PMID- 3338512 TI - Effects of triiodothyronine replacement on the anemia of chronic renal failure. AB - Patients and/or experimental animals with chronic renal failure have decreased serum levels of triiodothyronine (T3), a hormone well known for its erythropoietic activity. The following studies were designed in order to determine whether this observed abnormality in T3 metabolism is an important contributory factor to the etiology of the anemia of uremia. Groups of rats were made chronically uremic by a standard 5/6 nephrectomy technique and received slightly above physiological doses of T3 either by intermittent S.C. injections (twice daily) or by continuous infusion from intraperitoneally implanted osmotic minipumps. After 2 weeks of such treatment, and despite a normalization of serum T3 levels, there were no significant changes in the hematocrit, individual red cell mass, or serum erythropoietin levels of the uremic animals given T3 compared to control rats. We conclude that (1) the decreased serum T3 levels observed in uremia are not an important contributory factor to the pathogenesis of the anemia, and (2) treatment with replacement doses of T3 does not result in significant improvement of erythropoiesis. PMID- 3338513 TI - Effect of lung surfactant on the release of factor increasing monocytopoiesis by macrophages. AB - Upon ingestion of particulate and soluble material, at the site of an inflammation macrophages release the factor increasing monocytopoiesis (FIM), which accelerates the rate of division of the monoblasts and promonocytes in the bone marrow. It is not known, however, whether FIM is released by macrophages present at noninflamed sites. Since FIM is secreted only during phagocytosis and alveolar macrophages ingest surfactant in vivo, the present study was performed to find out whether surfactant induces the release of FIM by alveolar macrophages. Resident alveolar macrophages were found to contain FIM and secrete this factor in vitro in the absence of an introduced phagocytable particle. Resident peritoneal macrophages also contained FIM and released this factor after exposure to surfactant. These findings suggest that in the absence of an inflammatory stimulus in vivo, alveolar macrophages that have ingested surfactant release FIM to maintain the normal production of monocytes in the bone marrow. PMID- 3338514 TI - Effects of transplantation and age on immunohemopoietic cell growth in the splenic microenvironment. AB - Intact spleens from young adult and aged mice were transplanted into young recipients to compare effects of age and effects of spleen transplantation on hemopoietic and immune functions. Hemopoietic functions of histocompatible spleen transplants were assessed by partial cures of genetically anemic WBB6F1-Sl/Sld recipients, and immune functions were measured as numbers of anti-SRBC PFC(sheep red blood cell plaque-forming cells) and responses to the mitogen PHA (phytohemagglutinin). Spleens from WCB6F1 and WBB6F1 donors at least 28 months old partially corrected anemias in 10 of 28 Sl/Sld recipients, whereas spleens from 5- to 10-month-old donors performed significantly better, partially correcting anemias in 22 of 31 Sl/Sld recipients. B6D2F1 spleens were transplanted from either old or young donors in B6D2F1 recipients to test their ability to support immune-responsive cells. These spleen grafts were much smaller than recipient spleens and contained few anti-SRBC PFC. In contrast WCB6F1-+/+ spleens transplanted in Sl/Sld recipients were much larger, weighing more than the intact spleens of the recipients. Nevertheless when these spleens were from young donors, they contained only about 10% as many anti-SRBC PFC and PHA responsive cells as did recipient spleens, whereas old donor spleens contained even fewer. Use of splenectomized Sl/Sld recipients did not alter these results. Apparently the effect of transplantation was much more important than age in reducing the spleens' abilities to support immune-responsive cells. PMID- 3338515 TI - Kinetics of inhibition of CFU-C homing in long-term marrow culture. AB - We have previously shown that galactosyl- and mannosyl-BSA inhibit the binding of hemopoietic progenitor cells to their supporting stroma (homing) in long-term marrow culture, suggesting that the homing is mediated by a molecular recognition with galactosyl and mannosyl specificities. In the present work we studied the kinetics of this inhibition. In the absence of inhibiting reagents, total cell and CFU-C production continued linearly as a function of time in culture. When inhibiting reagents were incorporated at the time of initiation of cultures, cell and CFU-C production was halted, suggesting that the binding of progenitor cells to stroma was necessary for subsequent cell proliferation and differentiation. When inhibiting reagents were introduced 1 week after the initiation of culture, cell and CFU-C production continued at a much lower rate than that of control, suggesting that although the inhibiting reagents can inhibit the binding of progenitor cells to stroma, they are less effective in displacing those already bound. Finally, when the inhibiting reagents were removed from the cultures, cell and CFU-C production resumed at a rate similar to that of controls, indicating that these reagents do not alter the integrity of progenitor cell or stroma. PMID- 3338516 TI - Study of different phases in growth cycle of human bone marrow cells and their growth speed, using rat-human cell hybridization, premature chromosome condensation, and sister chromatid differentiation techniques. AB - The cytokinetic activity of bone marrow cells is an indication of hemopoietic status. In the routine examination of bone marrow smears, only M phase can be identified, whereas the different phases of the remainder of the cell cycle are not possible to determine. However, by using premature chromosome condensation and bromodeoxyuridine differential staining techniques, cell stage and cell kinetics can be easily determined. Ninety-eight samples of human bone marrow were collected, cells were hybridized with mitotic M3 cells, and 5016 randomly selected hybrid cells were analyzed for cell stage. Our data demonstrated that 80.37% of the cells were in G1 phase, 12.66% were in S phase, 5.29% were in G2 phase, and 1.68% were in M phase. In specimens that had been cultured for 48 h in the presence of bromodeoxyuridine, 57.46% had completed at least two rounds of DNA replication. In 72-h specimens, 69.27% of the cells had completed at least two S phases. In 96-h specimens, 2S and 2S+ cells occupied 74% of the cell population. The use of cell hybridization techniques, premature chromosome condensation, and bromodeoxyuridine-dependent differential staining revealed the phases of the cell cycle distinctly, as well as the kinetics of cell growth. PMID- 3338517 TI - Stem cell number versus the fraction synthesizing DNA. AB - It has been widely held that the fraction of spleen colony-forming units (CFU-S) in DNA synthesis is inversely correlated with CFU-S numbers. In 750 measurements the expected negative slope of the linear regression of CFU-S in S-phase on CFU-S was found to be significant only when the measurements from irradiated mice were pooled. In contrast, a significant positive correlation was observed when the measurements from normal controls were pooled. A hypothesis is offered to account for the variable relationship between CFU-S and CFU-S in S. The hypothesis fully recognizes the crucial role of both parameters in normal and regenerative hemopoiesis. PMID- 3338519 TI - Experimental allergic encephalomyelitis: a neurourological study. AB - To assess the neurourological disturbances produced by the perivascular inflammatory process in the acute phase of experimental allergic encephalomyelitis, we carried out a controlled study. Forty-six New Zealand male rabbits were inoculated with an encephalitogenic preparation. Twenty-seven of them developed neurological deficits in an average of 9.3 days postinoculation. A sample of 19 subjects was used as a control. The subjects were studied within 2 days after the manifestation of the first sign of encephalomyelitis. An average of eight successive cystosphincterograms were recorded. Their entire central nervous system was removed intact and suspended in 10% neutral buffered Formalin solution for 2 weeks, then cut into segments, embedded in paraffin, and finally stained with hematoxylin-eosin and Luxol Fast Blue. The results demonstrated a significant reduction of mean vesical capacity, maximum urethral pressure, and mean urethral pressure in the group with encephalomyelitis. Furthermore, we found a significant negative correlation between the average number of cellular perivascular infiltrates in the spinal sacral segment and urethral pressures. The results showed a significant negative correlation between supreamesencephalic inflammation and mean vesical capacity. PMID- 3338518 TI - Morphology of cells grown in the CFU-GEMM tissue culture assay from mononuclear cells obtained from peripheral blood and bone marrow of normal volunteers. AB - In ten healthy volunteers studies were done to assess the morphology, immunocytology, and cytochemical properties of mononuclear hematopoietic stem cells isolated from normal human peripheral blood and bone marrow grown in semisolid matrix mixed lineage colony-forming unit (CFU-GEMM) culture. In three volunteers, peripheral blood and bone marrow samples were collected simultaneously; the progeny were remarkably similar in each of the three paired cultures, although macrophages were more numerous in the bone marrow cultures. Three peripheral blood samples were cultured following frozen storage with 10% DMSO at-150 degrees C for approximately 5 months. Megakaryopoiesis was present in each case, demonstrating the full hematopoietic potential of previously frozen peripheral blood mononuclear cells. Four other peripheral blood samples and one bone marrow sample were cultured and, in each case, cells of all hematopoietic cell lines were present. Bone marrow, peripheral blood mononuclear cells, and previously frozen peripheral blood mononuclear cells grown in the CFU-GEMM tissue culture assay showed the presence of granulocyte-macrophage, erythroid, and megakaryocytic cell lines. PMID- 3338520 TI - Ascending fiber projections from the midbrain central gray to the ventromedial hypothalamus in the rat. AB - In 18 urethane-anesthetized ovariectomized female rats, 54 neurons in and around the hypothalamic ventromedial nucleus were transynaptically activated by electrical stimulation of the mesencephalic central gray matter. Ventromedial nucleus afferents from either the dorsal longitudinal fascicle (N = 10) or the medial forebrain bundle (N = 8) were disrupted by a small knife cut. In animals which lacked inputs from the dorsal longitudinal fascicle by a cut posterior to the ventromedial nucleus, transynaptic activation followed central gray stimulation in 20 cells; 26 cells were driven from the central gray in animals deprived of afferents through the medial forebrain bundle by a cut placed laterally to the ventromedial nucleus. Two patterns of synaptic activation followed electrical stimulation at 0.5 Hz: one type of response occurred during a latency range of 4 to 20 ms with fluctuation of each response less than 5 ms, the other type was characterized by diffuse activation for 50 ms following central gray stimulation. It was noted that the former time-locked response occurred in 19 among 20 cells in the posterior-cut animals, and the latter diffuse response was seen in 20 of 26 cells in the lateral-cut animals. Electrical stimulation of the ventromedial nucleus in another group of seven animals with the posterior cut caused antidromic activation of 19 central gray cells at latencies of 4.8 to 21.0 ms. Thus, central gray axons in the medial forebrain bundle were shown to have direct access to the ventromedial nucleus and multisynaptic pathways intervened for those in the dorsal longitudinal fascicle. PMID- 3338521 TI - A triggered hyperkinesia induced in rats by lesions of the corpus striatum. AB - The role of the corpus striatum (caudate, putamen, and globus pallidus) in movement control has been suggested to involve the modulation of sensory traffic to downstream motor mechanisms. We report that kainic acid lesions of the posterior corpus striatum, which preferentially spare fibers of passage while destroying striatopallidal neurons, produce a stimulus-sensitive movement pattern in rats that has a highly specific sensory trigger. The triggered choreic movement pattern is not a motor pathology per se, nor a response to diffuse states of arousal or stress, but rather is activated specifically in response to oral sensory stimulation. This sensory-specific hyperkinesia may be relevant to certain human sensorimotor pathologies. PMID- 3338522 TI - Firing and contractile properties of human lower lip motor units during sustained isometric contractions. AB - Human subjects were taught to generate constant forces with their lips by contracting across a pair of hooks which held the corners of the mouth fixed in place. The force was measured with a strain gauge attached to one of the hooks. The activity of single motor units was recorded during production of small to near maximal levels of force. The recruitment and firing patterns of each unit were observed, and in vivo contractile properties of each unit were estimated using spike-triggered averaging of the high-gain force record. Recruitment of units was observed at all levels of force and recruitment level varied from trial to trial for each unit. Interspike interval variability was high at all levels of force. The twitch tensions of the units were all less than 10 g; the contraction times ranged from 16 to 90 ms. It is hypothesized that the differences between lip and limb motor unit properties in this task reflect the mechanical, anatomic, and neurophysiologic differences between these systems. PMID- 3338523 TI - Comparison of posttranslational protein modification by amino acid addition after crush injury to sciatic and optic nerves of rats. AB - Posttranslational protein modifications by the addition of amino acids are reactions which occur in intact sciatic and optic nerves of rats. The nerves differ, however, in that 2 h after crush injury these reactions are activated in sciatic but not in optic nerves. As sciatic nerves will eventually regenerate, whereas optic nerves will not, we have proposed that the activation of these reactions is correlated with the ability of a nerve to regenerate. The current experiments examined the posttranslational addition of amino acids to proteins at times greater than 2 h after nerve crush, during sciatic nerve regeneration and optic nerve degeneration. We also examined the optic nerve for morphologic correlates to changes in protein modification and partially characterized the proteins modified by [3H]Lys in the regenerating sciatic nerve using two dimensional sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). In a segment of sciatic nerve taken from a region just proximal to the site of crush, protein modification by covalent addition of [3H]Arg, [3H]Lys and [3H]Leu increased during both posttraumatic (2 h postcrush) and regenerative (6 days and 14 days postcrush) stages. Two-dimensional PAGE of [3H]Lys modified sciatic nerve proteins 6 days after crush injury showed labeling of proteins having molecular masses in the 18,000- to 20,000-, 30,000- to 40,000-, and 80,000 to 100,000-Da ranges, with neutral or basic isoelectric points (pI 7.1 to 8.0). In the retinal portion of the crushed optic nerve, incorporation of the same amino acids was unchanged or depressed to 21 days postcrush, except at 6 days postcrush when the incorporation of all three amino acids into proteins was increased threefold. These increases correlated with the appearance of terminal end bulbs in the portion of nerve analyzed. Histological examination of each nerve 2 h postcrush showed marked edema in the optic but not the sciatic nerve, a condition which may be related to the ability of sciatic and inability of optic nerves to activate protein modification reactions. PMID- 3338525 TI - Role of gender in the behavioral effects of peripheral sympathetic ingrowth. AB - Following cholinergic denervation of the hippocampal formation, peripheral sympathetic nerves originating from the superior cervical ganglia grow into the hippocampus. As gender is known to alter the anatomy of hippocampal sympathetic ingrowth, we assessed the effect of this variable on the behavioral recovery following ingrowth. Adult male or female rats were trained on a standard version of a radial-8-arm maze task until they reached a specific learning criterion. Animals from each sex then underwent one of three surgical procedures: sham surgery, medial septal lesions plus superior cervical ganglionectomy, or medial septal lesion plus sham ganglionectomy. Reacquisition of the maze was then assessed. Prior to surgery, male animals acquired the task significantly faster than female animals. Following surgery male and female rats recovered overall performance at similar rates. However, marked group differences were observed. In males, the control group recovered faster than the group with medial septal lesion plus ganglionectomy, which recovered faster than the medial septal lesion group. In females, the control group recovered faster than the medial septal lesion group, which in turn recovered faster than the medial septal ganglionectomy group. The results of this study clearly demonstrate that gender can influence the behavioral effects of hippocampal sympathetic ingrowth. We believe that this is the first report in which gender has been shown to alter the behavioral effect of a neuronal reorganization. PMID- 3338524 TI - Proportion and location of spinal neurons receiving ventral root afferent inputs in the cat. AB - Spinal neurons receiving ventral root afferent inputs were investigated in anesthetized and paralyzed cats. We were concerned with the afferent fibers in the ventral root that travel distally and then enter the spinal cord through the dorsal root. The questions to be answered included the proportion and distribution of spinal neurons receiving ventral root afferent inputs and their peripheral input characteristics. The 1.7 ventral root was cut near the spinal cord and the distal stump was stimulated while making a systematic search for neurons in the entire gray matter of the ipsilateral spinal cord that responded to the stimulation. The following conclusions were made: (i) the afferent fibers in the cat ventral root enter the spinal cord through the dorsal root and evoke a variety of responses (excitation, inhibition, or mixed) in a large proportion of spinal neurons (about 20%): (ii) these responses seem to be mediated largely by spinal mechanisms: (iii) spinal neurons receiving ventral root afferent inputs are situated in a wide region of the ventral spinal cord: (iv) ventral root fibers in a single root enter the spinal cord and exert their responses over a large region of the spinal cord (at least two spinal segments rostrally and caudally): (v) some of the spinal neurons that responded to ventral root stimulation were found to be ascending tract cells, suggesting that ventral root afferent inputs can reach supraspinal structures: (vi) ventral root afferent fibers converge onto spinal neurons that have a variety of peripheral receptive field characteristics: and (vii) with some exceptions, most neurons receiving ventral root inputs were excited best by mechanical and/or thermal noxious stimuli applied to the periphery. PMID- 3338526 TI - Comparison of automatic and voluntary chewing patterns and performance. AB - Chewing, like respiration, is ordinarily performed as an automatic motor act, yet both can be voluntarily controlled. No in-depth analyses of voluntary chewing exist. Therefore, we have analyzed on a cycle-by-cycle basis voluntarily controlled chewing, and compared it with automatic chewing. We assessed the performance during voluntarily controlled chewing by obtaining constant error and variable error scores. Nine healthy adults with full dentition were subjects (Ss). Their three-dimensional jaw movements and movement times were derived from Kinesiograph recordings obtained while chewing a standard piece of gum on the right side of the mouth. Burst durations and onset latencies of masseter activity were obtained from surface-recorded EMGs. Frequency during automatic chewing was obtained from data recorded while the subject viewed a film. Next, the subject chewed in time with a metronome set at this "automatic" rate. Intrasubject variability among 30 consecutive chewing cycles during voluntary was less than during automatic chewing. In every S gape and ipsilateral jaw excursions and the variability of burst durations of masseter activity were less during voluntary than during automatic chewing, showing that both the spatial and temporal aspects of the two types of chewing differ significantly. Ss varied in ability to follow the metronome. A S's constant error might be small, yet his variable error might be large, as if feed-back-based corrections influenced cycle-to-cycle variability. Fast chewers had smaller constant and variable error scores than did slow chewers, suggesting a speed-accuracy relationship. In summary, both temporal and spatial aspects of voluntary chewing were modified compared with those of automatic chewing. During voluntarily controlled chewing, cycle-to-cycle variability was less compared with automatic chewing due to reductions in variability of occlusal phase and the masseter's burst durations, and total jaw excursions were less because gapes and ipsilateral deviations during closing were reduced. PMID- 3338527 TI - Influence of visual deprivation on the visual and oculomotor system: acetylcholinesterase activity in oculomotor neurons. AB - The effects of visual deprivation (dark-rearing) on neurons in both the visual and oculomotor systems of black mice were studied using morphologic and histochemical techniques. In the neurons of the dorsal nucleus of the lateral geniculate body, the cytoplasm of dark-reared mice was less developed and the cytoplasm/nucleus ratio was significantly smaller in the dark-reared mice than in the controls. In contrast, large motoneurons in the oculomotor nucleus did not show any ultrastructural changes and the cytoplasm/nucleus ratio was normal. However, in large motoneurons of dark-reared mice, acetylcholinesterase (AChE) positive areas were scattered in the cytoplasm, and the ratio of the AChE positive areas to the cytoplasm area was significantly smaller than that in the controls. PMID- 3338528 TI - Cortical asymmetry--a preliminary study: neurons-glia, female-male. AB - Previous studies on human cortical area 39 suggested that neuron:glial ratios differed between the sexes. These findings were the inspiration for the present investigation which dealt with neuronal and glial counts in area 39 in the male and female rat cerebral cortex. Transverse, celloidin or frozen sections, were cut from male and female brains (respectively) from 90-day-old Long-Evans rats. Neurons and glia were counted on enlarged photographs of stained sections, including area 39, with 35-mm Kodak Panatomic-X film using a Zeiss photomicroscope (X400). Five-by-three-inch prints were taped together in sequence to yield a 640X enlarged "montage" of area 39. Five cell types were differentiated with reference to a standard: neurons, astrocytes, oligodendrocytes, "dark astrocytes," and unidentified glia. The data were analyzed with a two-way analysis of variance (ANOVA: five cell types by two hemispheres). Student's t test and a paired t test were used when appropriate. The neuron:glial ratios in the male rats were consistently higher than those in the females in both hemispheres. The male right side had 12% (P less than 0.05) more neurons than the left; the female had 13% (P less than 0.05) more neurons on the left than the right. Similar, but not identical, asymmetrical patterns were seen with the glial cells. PMID- 3338529 TI - Influence of anesthesia on spontaneous activity and receptive field size of single units in rat Sm1 neocortex. AB - Spontaneous and cutaneously driven unit activity was recorded in the hindfoot region of rat Sm1 neocortex under controlled intravenous infusion, at three selected rates, of the steroid anesthetic agent Althesin. Increasing depth of anesthesia decreased average spontaneous firing rates of 67 single units from 2.5 to 11 Hz during light anesthesia to 0 to 2.5 Hz in deep anesthesia. Thresholds to cutaneous stimulation for 58 units were innocuous (from 15 to 190 micron) using a 5-ms ramp displacement of the skin in the center receptive field. Responses from 13 sites on the hindfoot were classified according to response probability for each of the 58 units in reply to stimuli at 1.5 times center receptive field threshold. Small receptive fields were seen only under conditions of deep anesthesia, considerable expansion of both center and excitatory surrounds occurring with lighter anesthesia. Mean values for total receptive field size (center plus surround excitatory receptive field) were 10.8, 7.8, and 3.4 sites, respectively, for light, moderate, and deep anesthesia. The size of the receptive field was also influenced by stimulus repetition rate; moderate increases of this and anesthetic depth could eliminate substantial receptive fields. Surround inhibition of evoked activity was more effective in deeper anesthesia with little effect in light anesthesia. We suggest that receptive field expansion in light anesthesia arises from a relative increase in excitability of afferent pathways and an accompanying increase in the preponderance of surround excitation vis a vis surround inhibition. PMID- 3338531 TI - Influence of malnutrition on developing rat peripheral nerves. AB - Animals with experimentally induced neuropathies frequently fail to gain weight normally and appear poorly nourished. To determine whether or not malnutrition alone contributes to peripheral nerve dysfunction in these disorders, we subjected healthy 40-day-old rats to three grades of food restriction. After 4 weeks, food-restricted rats weighed 203 +/- 5 (mean +/- SE), 152 +/- 12, and 97 +/- 5 g, respectively, whereas control rats having free access to food weighed 379 +/- 22 g. Posterior tibial nerves of food-deprived rats had smaller endoneurial areas, fewer large-diameter fibers, and shorter internodes than did the nerves of control animals. However, the number of fibers was similar to controls, and there was no evidence of active degeneration or demyelination. Motor and mixed nerve conduction velocities along the same nerves increased with age and did not differ among control and malnourished groups. In growing rats, food deprivation sufficient to impair somatic growth interferes with the maturation of large-caliber myelinated fibers, but does not effect standard electrophysiologic measurements of nerve function. PMID- 3338530 TI - Postural responses of normal geriatric and hemiplegic patients to a continuing perturbation. AB - The electromyographic (EMG) activity of the gastrocnemius and tibialis anterior muscles was recorded from normal geriatric subjects and from hemiplegic patients subjected to a continuous back-and-forth movement of the platform on which they stood. The platform oscillated at a fixed frequency of 0.5 Hz. Movement amplitude was the largest each patient could withstand without support of the hands. Standing on the moving platform continued for 5 min. EMG recordings continued for 60 s, commencing 2 min after movement onset. Analysis of the EMG, in normal subjects revealed a typical pattern of reciprocal activity in the tibialis anterior and gastrocnemius, in synchrony with the back-and-forth movements of the platform. The cyclic activation of each muscle started before movement of the platform could cause its stretch. The normal movement-induced pattern of leg muscle activation was greatly disturbed or totally absent in hemiplegic patients. In such patients, various patterns of tonic activation of one or both muscles were observed in the sound as well as the afflicted leg. Occasional periodic activation of one muscle or the other was observed. However, such activation was not well synchronized with movement of the platform and did not last long. Based on the above observations, we concluded that the ability to adapt to a rhythmic platform movement by production of anticipatory phasic muscular contractions is severely disrupted in hemiplegics. PMID- 3338532 TI - Physiological identification of afferent fibers and postsynaptic sensory neurons in the spinal cord of the intact, awake cat. AB - A method was developed to record from spinal cord cells in the awake, intact, partially restrained cat. Units were classified as afferent fibers or postsynaptic cells based on their ability to follow 100-Hz peripheral stimulation, the duration and configuration of the action potential waveform, and the number of spikes evoked by a single electrical pulse. These criteria are supported by independent observations of the location of the recording site, size of the receptive field, and adequate stimulus. Of 84 cutaneously activated units, 29 were classified as afferent fibers, 28 as postsynaptic cells, and 27 were not classified. No cutaneously activated unit was spontaneously active. In contrast, all 28 units (7 postsynaptic and 21 not classified) responding to joint position or movement were spontaneously active (5 to 40 Hz). No unit responded to both cutaneous and proprioceptive inputs. Evidence for convergence of cutaneous input from different types of receptors was limited to five postsynaptic neurons that responded to hair movement and to stimuli applied to the skin; two of these cells responded differentially to noxious pinch. Two of 24 postsynaptic cutaneous units ceased responding to electrical cutaneous stimuli when the cat was eating. The responses of 29 primary afferent fibers were not altered by the behavior of the cat. These results suggest that, in the awake cat (i) criteria based on neuronal responsiveness and action potential waveform can be used to distinguish adequately between afferent fibers and postsynaptic cells; and (ii) there is a tonic inhibitory control, greater than in the anesthetized or spinally transected cat, that varies with behavioral state and is directed primarily at spinal neurons receiving cutaneous input. PMID- 3338533 TI - Effects of etoposide-induced blood-brain barrier disruption on brain water, intracranial pressure, and cerebral vasomotor tone. AB - This study investigated the effects of hypertension and water loading on etoposide-induced, reversible blood-brain barrier disruption in a rat model. Twenty-nine animals were divided into four groups: group 1--intracarotid (i.c.) injection of saline followed in 1 h by 5 ml i.c. water; group 2--i.c. etoposide followed by i.c. water; group 3--i.c. saline followed by i.v. metaraminol to increase systemic blood pressure; group 4--i.c. etoposide followed by i.v. metaraminol. Systemic blood pressure and intracranial pressure were monitored continuously. Evans blue staining of the brain was used as a monitor of blood brain barrier disruption. Animals were killed 1 h after either aramine or water infusion, and the brains removed and inspected for the degree of disruption. After dehydration, brain water was calculated for each hemisphere. Two-thirds of the animals infused with etoposide had evidence of barrier disruption, whereas none of the control animals infused with saline were disrupted. Neither control groups 1 or 3 showed significant change in intracranial pressure after water loading or augmentation of systemic blood pressure, respectively. Group 4 animals failed to demonstrate any significant change in intracranial pressure despite marked barrier disruption and acute hypertension (within the limits of normal autoregulation). A small but statistically significant increase in intracranial pressure was noted in group 2 animals with the greatest degree of barrier disruption. A significant increase in brain water was observed ipsilateral to etoposide infusion in only those animals with the most marked barrier disruption. These results indicate that etoposide-induced blood-brain barrier disruption caused significant increases in brain water without significant alteration of cerebral vasomotor tone or increases in intracranial pressure after water loading except in the most severe disruption. The classic untoward consequences of vasogenic edema were not encountered in the present model. PMID- 3338534 TI - Phosphatidylserine increases in vivo the synaptosomal uptake of exogenous GABA in rats. AB - A sonicated liposome suspension of gamma-aminobutyric acid (GABA) and phosphatidylserine (liposome-entrapped GABA), intraperitoneally administered in rats, inhibited EEG epileptic activity induced by penicillin, whereas GABA did not. A significant increase (20.4%) in brain radioactivity accumulation occurred at 5 min after i.p. administration of [14C]GABA associated with phosphatidylserine in comparison with the administration of [14C]GABA; such an increase persisted after 20 min. However, the accumulation of radioactivity into brain synaptosomes demonstrated a 24.1% increase at 5 min and subsequently showed a 43.3% increase at 20 min after injection of liposome-entrapped GABA. The above findings suggest that phosphatidylserine stimulates exogenous GABA uptake into brain GABAergic nerve terminals. PMID- 3338535 TI - Unitary activity in the suprarhinal cortex of the rat and its modulation after lateral amygdala stimulation. AB - Unitary responses in the suprarhinal cortex were studied in anesthetized rats. Lateral amygdala stimulation gave rise to two types of cortical responses: (i) an excitatory response (59%) characterized either by a single spike discharge, or by a burst of two to four spikes, or (ii) an inhibitory response (41%) affecting cortical neurons which exhibited spontaneous discharge. The duration of inhibition appeared to be related to the intensity of stimulation and the spontaneous discharge frequency. PMID- 3338536 TI - Effect on the rat hypoglossal nucleus of vinblastine and colchicine applied to the intact or transected hypoglossal nerve. AB - The possibility that interruption of axonal transport in otherwise intact axons induces retrograde neuronal and nonneuronal reactions was examined. In addition, the proposal that blockade of axonal transport proximal to nerve injury might inhibit or delay the axon reaction was examined. Cuffs containing various doses of vinblastine were applied to the intact hypoglossal nerve. Colchicine was applied in a similar way to the intact hypoglossal nerve, injected directly into the intact nerve, or administered proximal to the site of hypoglossal nerve transection. The effect on retrograde axonal transport in the nerve was evaluated in the vinblastine experiments by the retrograde horseradish peroxidase (HRP) technique following injection of HRP or wheat germ agglutinin-conjugated HRP into the tongue. A dose of 0.01% caused an almost complete, but transient, blockade of the retrograde transport of the tracer, and induced a clearcut chromatolytic reaction in hypoglossal neurons. The chromatolytic changes were accompanied by a significant increase in the number of glial cells, many of which were identified as microglia. Similar results were obtained with colchicine alone or in combination with nerve transection. Signs of Wallerian degeneration after vinblastine treatment (0.01%) were observed only in a small number of myelinated fibers. The findings are compatible with the view that depletion of retrogradely transported factors from the peripheral innervation territory (including the distal nerve stump) to the perikaryon and/or a premature return of anterogradely transported substances at the site of drug exposure are factors inducing retrograde neuronal and nonneuronal changes. PMID- 3338537 TI - Myotrophic effects on denervated fast-twitch muscles of mice: correlation of physiologic, biochemical, and morphologic findings. AB - Certain morphological, biochemical, and physiological parameters were assessed in fast-twitch muscles of 6-week-old mice with unilateral hindlimb denervation for 4 weeks. Some of the mice received daily injections (i.p.) of nerve extract throughout the period of denervation. Values from treated and untreated denervated muscles were compared with each other and with those from contralateral, innervated controls. The cross-sectional areas of denervated types IIA and IIATy muscle fibers were 45% and 28% greater, respectively, in muscles of treated than of untreated mice, which resulted in greater maximal tetanic tension. Injection with nerve extract did not influence the postdenervation reduction of phosphorylation of myosin light chain 2-fast nor the loss of posttetanic twitch potentiation, two parameters thought to be related. Denervation produced a significant decrease in relative content of cytosolic parvalbumin; however, this change was completely prevented by administration of nerve extract. This latter finding correlated with the amelioration of greater than 50% of the postdenervation prolongation of half-relaxation time of the twitch in treated than in untreated muscles. More than half of the prolongation of time-to-peak of the twitch was also prevented in denervated muscles of treated than of untreated mice. PMID- 3338538 TI - Effect of alpha-melanocyte-stimulating hormone on peripheral nerve regeneration in the rat: histological aspects and comparison with the effect of gangliosides. AB - Recovery that follows a sciatic nerve crush was studied by counting the number of myelinated axons in cross sections of the sciatic nerve at various times after operation. Treatment with alpha-MSH (10 micrograms/animal, s.c., every 48 h) resulted in an increased number of myelinated axons 10 days after a sciatic nerve crush (3 mm distal to the crush). At postoperation day 22, alpha-MSH increased the number and diameter of axons 20 mm distal to the crush, but 3 mm distal to the crush no effect of alpha-MSH was seen. Treatment with gangliosides (50 mg/kg, i.p., daily) had a somewhat different effect: the number of axons was increased at a later stage and at all distances from the crush. The effect of gangliosides on the axonal diameter was opposite that of alpha-MSH: treatment with gangliosides stimulated the formation of axons with a smaller diameter. PMID- 3338539 TI - Differential inhibition produced by peripheral conditioning stimulation on noxious mechanical and thermal responses of different classes of spinal neurons in the cat. AB - The effect of conditioning stimulation of a peripheral nerve on responses of spinal neurons (dorsal horn cells and motoneurons) was studied in 16 decerebrate spinal cats. The activity of dorsal horn cells was recorded with a microelectrode at the lumbosacral spinal cord and the single-unit activity of motoneurons was recorded from a filament of ventral rootlet divided from either the L7 or S1 ventral root. The responses of spinal neurons were evoked by noxious and innocuous mechanical stimuli and by noxious thermal stimuli applied to the receptive fields. The peripheral conditioning stimulation was applied to the tibial nerve with repetitive electrical pulses (2 Hz) at an intensity either suprathreshold for A delta or C fibers for 5 min. Applying conditioning stimulation to a peripheral nerve produced a powerful inhibition of the responses elicited by noxious stimuli, suggesting this inhibition is an antinociceptive effect. The inhibition produced by peripheral conditioning stimulation was differentially greater on the responses to noxious than to innocuous stimuli. Based on the results obtained from conditioning stimulation with graded strengths, afferent inputs from both myelinated and unmyelinated fibers seem to contribute to the production of the antinociceptive effect. The magnitude of the antinociceptive effect is bigger for the responses to noxious thermal than to mechanical stimuli. Furthermore, the reflex activity recorded in motor axons seemed to be more sensitive than in dorsal horn cells to the antinociceptive effect. PMID- 3338540 TI - Extracellular unit responses in the pulvinar-lateral posterior complex of the cat through electrical stimulation of substantia nigra reticulata and lateralis. AB - Extracellular single-unit responses of neurons in the ipsilateral pulvinar lateral posterior complex were recorded in 10 encephale isole cats with stimulating electrodes implanted in the substantia nigra pars reticulata and pars lateralis. Fifteen percent of 101 pulvinar-lateral posterior complex thalamic neurons increased their spike discharges when the substantia nigra was stimulated and none decreased its activity. The excitatory effect of this stimulation is discussed in relation to the eventual excitatory or inhibitory character of the efferent projection from the substantia nigra pars reticulata and lateralis to the pulvinar-lateral posterior complex. PMID- 3338541 TI - Dystrophic chick brain lacks a particular neurotrophic factor. AB - Extracts from normal embryonic chick brain act as "trophic" agents in the newt blastemata assay where they stimulate the incorporation of amino acids into protein. Equivalent extracts prepared from the brains of dystrophic (am/am) chick embryos are apparently devoid of any equivalent activity. PMID- 3338542 TI - Leishmania braziliensis panamensis: increased infectivity resulting from heat shock. AB - Promastigotes of Leishmania braziliensis panamensis were subjected to a heat shock transformation yielding an amastigote-like stage. During the process of conversion, the heat-induced differentiating form displayed an increase in infectivity (as determined by lesion size) accompanied by a total protein composition unlike that of the promastigote and a morphology resembling that of the amastigote. These biological/functional changes may be related to an involvement of a heat shock response in the differentiation of leishmania, thus having important implications in the development of prevention and treatment stratagems. PMID- 3338543 TI - Schistosoma japonicum and Paragonimus ohirai: antagonism between S. japonicum and P. ohirai in Oncomelania nosophora. AB - Antagonistic interactions between Schistosoma japonicum and Paragonimus ohirai were examined in the snail host, Oncomelania nosophora. When P. ohirai-infected snails were exposed to S. japonicum miracidia at intervals of 4 to 18 weeks post first exposure, only a few snails (0-7%) were found to be superinfected with S. japonicum sporocysts. Sporocysts were fewer in number than those of single infected controls. Mature S. japonicum cercariae were not observed. Furthermore, when the snails were examined at intervals of 14 to 18 weeks post-second exposure, neither sporocysts nor cercariae of S. japonicum were found. On the other hand, when the snails were exposed to miracidia of S. japonicum and P. ohirai simultaneously, they were easily infected with both parasites. At 26 weeks after simultaneous exposure, however, the infection rate of S. japonicum was significantly lower than that of controls. In contrast, when S. japonicum infected snails were exposed to P. ohirai miracidia, they were superinfected with P. ohirai, although the infection rate was somewhat lower than that of controls. These results indicate the existence of antagonism between S. japonicum and P. ohirai in O. nosophora. Furthermore, P. ohirai was dominant over S. japonicum in the antagonistic interactions in this snail host. PMID- 3338544 TI - Trypanosoma brucei: susceptibility to hydrogen peroxide and related products of activated macrophages. AB - The susceptibility of procyclic, trypsinized, or bloodstream forms of Trypanosoma brucei to lysis by hydrogen peroxide and by activated mouse macrophages was investigated in vitro using the release of biosynthetically labeled proteins as an assay. Uncoated parasites were more resistant than coated bloodstream forms in both cases. Macrophage trypanolysis upon triggering with phorbol myristate acetate occurred extracellularly and seemed to depend on the release of hydrogen peroxide, as it was prevented by catalase. However, when presented trypanosomes in presence of fresh immune serum which was itself lytic, macrophages did not show any additional lytic effect, and phagocytosis was related to already damaged parasites. PMID- 3338545 TI - [The pathogenicity of free-living amoebae isolated from the intestinal tract of reptiles]. PMID- 3338546 TI - Fasciola hepatica: perturbation of secretory activity in the vitelline cells by the sodium ionophore monensin. AB - The effect of the sodium ionophore monensin on the vitelline cells of Fasciola hepatica has been determined both in vitro and in vivo by means of transmission electron microscopy. In intact flukes in vitro, vacuolation of the Golgi complex of the intermediate, shell protein secreting vitelline cells is evident after 1.5 hr incubation in monensin (1 X 10(-6) M). The vacuolation becomes progressively greater with time, eventually spreading to the late stem cells and mature cells. In addition, there is a block in the normal migration of the shell protein globules to the periphery, the shell globule clusters becoming very loosely packed and empty, and distended single globules accumulate in the perinuclear region of the cell. Disruption of the nurse cell cytoplasm is apparent from 6 hr onwards, giving the follicle a less compact appearance. Morphological changes induced by higher concentrations of monensin (up to 1 X 10(-4) M) followed a similar time course and pattern to that described for 1 X 10(-6) M) followed a similar time course and pattern to that described for 1 X 10(-6) M. In tissue slice material (1 X 10(-6) M) these effects of monensin are evident more rapidly, and to a far greater extent: the condition of the vitelline cells in slices after only 1.5 hr resembles that reached in intact flukes after more than a 12-hr incubation. Incubation in ouabain, an inhibitor of Na+/K+-ATPase activity, has little effect on vitelline morphology over a 6-hr period (1 X 10(-3) M), although brief (0.5 hr) exposure to ouabain followed by monensin treatment (1 X 10(-4) M, 3 hr) does lead to gross vacuolation of the intermediate cells, the condition resembling that in tissue-slice material. In contrast, in vivo treatment of infected laboratory rats (1 X 5 mg/kg) only leads to a transient effect on the ultrastructure of the intermediate vitelline and nurse cells. The specific perturbation of the Golgi complex and secretory traffic in the vitelline cells of F. hepatica by monensin follows the classic pattern observed in other cell types. PMID- 3338547 TI - Schistosoma mansoni: praziquantel-induced changes to the female reproductive system. AB - The long-term in vivo effects of a single subcurative dose (200 mg/kg body wt of mouse) of praziquantel on the ultrastructure of the female reproductive system of Schistosoma mansoni were investigated. Morphological changes in the structure of both the vitelline gland and the ovary were apparent within 24 hr post-treatment, and lead to a partial or complete regression of both organ systems. Associated with this regression was a cessation of egg production. In surviving, paired females, irrespective of the initial severity of the drug-induced damage, both the vitelline gland and the ovary completely redeveloped and lead eventually to a resumption of egg production. In contrast, in unpaired, previously mature females the reproductive system also regressed but did not redevelop. In these cases, although the initial changes in the reproductive system were the result of drug action, the long-term regressive changes were due to discontinued male stimulation. PMID- 3338549 TI - Nippostrongylus brasiliensis: histochemical changes in the composition of mucins in goblet cells during infection in rats. AB - Changes in the quality of mucins in jejunal goblet cells were investigated during an infection with Nippostrongylus brasiliensis in rats. At 10 days after infection, when proliferative activity in the crypts is excessive and both crypts and villi are characterized by hyperplasia of goblet cells, the histochemical composition of the population of goblet cells in comparison with controls shows a marked increase in crypt and villous goblet cells containing neutral mucins. At 15 days after infection both crypts and villi display a significant increase in goblet cells containing acid mucin and decrease in goblet cells containing neutral mucin. The acid mucins in crypt and villous goblet cells on day 15 appear to be sulphomucins predominantly, whereas in controls sialomucin-containing goblet cells dominate both in the crypts and on the villi. These experiments establish that the explusion of N. brasiliensis from the intestine of the rat coincides not only with quantitative, but also with remarkable qualitative changes in the histochemical composition of mucins in goblet cells. PMID- 3338548 TI - Hymenolepis muris-sylvaticae and H. microstoma: immunological cross-reaction in mice. AB - A primary infection with Hymenolepis microstoma strongly protects against cross infection with H. muris-sylvaticae and also against secondary infection with H. microstoma in NMRI mice, resulting in an accelerated loss of worms and a weight reduction of the remaining worms. A primary infection with H. muris-sylvaticae causes an accelerated rejection of secondary infection with H. muris-sylvaticae but it has no effect on cross-infection with H. microstoma, neither with regard to worm recovery nor with regard to worm biomass. Determinations by enzyme-linked immunosorbent assay of antibody concentrations in the mouse sera revealed that: (1) the antibody response evoked by H. microstoma infection is much greater than by H. muris-sylvaticae infection; (2) a cross-infection with H. muris-sylvaticae boosts the antibody response evoked by H. microstoma infection; (3) H. microstoma antigen can be used to measure antibody concentration against both H. microstoma and H. muris-sylvaticae; and (4) although H. muris-sylvaticae is rejected faster in a cross-infection (i.e., after a primary H. microstoma infection) than in a secondary infection (i.e., after a primary H. muris-sylvaticae infection), antibodies evoked by the primary H. microstoma infection show little cross reaction with H. muris-sylvaticae antigen. This suggests that it is doubtful whether serum antibodies are the direct effectors in worm rejection. PMID- 3338550 TI - Trichobilharzia ocellata: interference with endocrine control of female reproduction of Lymnaea stagnalis. AB - Calfluxin (CaFl), one of the gonadotropic hormones of Lymnaea stagnalis, stimulates the influx of Ca2+ into the mitochondria of the cells of the albumen gland, one of the accessory sex organs of the snail. This effect is suppressed in glands of noninfected snails by an agent (schistosomin) present in the hemolymph of snails infected by Trichobilharzia ocellata as shown in in vitro experiments. The agent is present from 6 weeks postinfection onward. Ca2+ deposits in the mitochondria were demonstrated with the ultracytochemical antimonate precipitation technique. The percentage of Ca2+-positive mitochondria was taken as a measure for the effects of CaFl. This percentage appeared to be greatly reduced when glands were incubated in serum of infected snails (Sinf). The data showed that Ringer incubations can serve as controls for experiments with serum: no differences were found between Ringer incubations and incubations in either fresh or frozen serum of noninfected snails. Schistosomin was not affected by freezing, which enables cold storage of Sinf. The dose-response relationship of schistosomin shows that at a 1:2 dilution of Sinf with Ringer the response to CaFl was reduced more than 50%. Schistosomin is heat-stable and Pronase-labile, which indicates that it has a peptide nature. Probably schistosomin(s) is responsible for the reduction/cessation of fecundity in trematode-infected snails. PMID- 3338552 TI - Effects of female sex hormones on the activity of serum hyaluronidase. AB - The activities of serum hyaluronidase from female rats were measured during pregnancy. In pregnant female rats, the activity of serum hyaluronidase was found to increase initially and to fall to a minimum by the last day of the gestation period, but the activity of the enzyme increased after delivery and was similar to normals at 21 days post-partum. The activity of hyaluronidase obtained from bovine leucocytes was significantly increased when leucocytes were incubated with various concentrations of progesterone. It is suggested that female sex hormones affect lysosomal membranes making them lyse more readily and hence release hyaluronidase. PMID- 3338551 TI - Prothymosin alpha is a nuclear protein. AB - Prothymosin alpha, a protein first isolated from rat thymus and widely distributed in animal tissues, has an attributed role in the stimulation of the immune system. Its structure contains thymosin alpha 1, a Glu-rich domain and a putative nuclear location signal. Furthermore, the amount of this protein seems to be associated with the relative size of the nucleus and is inducible during cell growth. We postulate that prothymosin alpha is located inside the cell nucleus and that its activity might be to organize some protein complexes. PMID- 3338553 TI - Translocation of protein kinase C in porcine thyroid cells following exposure to thyrotropin. AB - We have previously shown that protein kinase C activators modulate differentiated thyroid function in vitro; however, how protein kinase C may be activated physiologically is unknown. The present studies were undertaken in order to determine whether TSH could activate protein kinase C in vitro. Following exposure of porcine thyroid cells to TSH, translocation of protein kinase C from the cytosol to its membrane-bound form was observed. Maximal translocation occurred at the lowest TSH concentration able to trigger this response (10 mU/ml) but persisted at higher concentrations (20-100 mU/ml). Time-course studies revealed that translocation of protein kinase C was seen only after 40 min. TSH could also produce a similar translocation in human neutrophils (known to have TSH receptors). In thyroid cells pre-treated with TSH, modulation of phorbol mediated protein kinase C translocation was noted. These results indicate that TSH causes the translocation of protein kinase C in porcine thyroid cells (and possibly other TSH receptor-containing cells) and therefore may regulate the action of protein kinase C on differentiated thyroid function. PMID- 3338554 TI - Stronger affinity of reticulocyte release factor than natural suppressor tRNASer for the opal termination codon. AB - Animal natural suppressor tRNA did not affect the release reaction of reticulocyte release factor (RF) at the same concentration of tRNA (both estimated as being present at a similar level of 3-5 X 10(-8) M in vivo); even at a 10-fold greater concentration the tRNA did not prevent the release reaction with RF. In order to confirm this result, the Ka values were determined. The Ka value between RF and UGA was 1.26 X 10(6) M-1 and that between the suppressor tRNA and UGA amounted to 8 X 10(3) M-1. This result showed that RF had a 150-fold stronger affinity than suppressor tRNA for the opal termination codon. Incorporation of phosphoserine into phosphoprotein via phosphoseryl-tRNA was inhibited by addition of RF to the reaction mixture. These results suggest that animal natural suppressor tRNA in the normal state does not perform its suppressor function, except in special cases where mRNA has the context structure near the opal termination codon (UGA). PMID- 3338555 TI - The human medulloblastoma cell line TE671 expresses a muscle-like acetylcholine receptor. Cloning of the alpha-subunit cDNA. AB - Nicotinic acetylcholine receptors (AChRs) from muscle bind alpha-bungarotoxin (alpha Bgt) and are composed of four kinds of subunits, whereas AChRs from mammalian brains do not bind alpha Bgt and are composed of two kinds of subunits. alpha Bgt-binding proteins whose function is unknown are also found in brain. All these proteins belong to the same gene family. The human medulloblastoma cell line TE671 expresses a functional AChR which binds alpha Bgt. Surprisingly, the AChR of this neuron-derived cell line has electrophysiological, immunological and biochemical properties different from neuronal AChRs and very similar to muscle AChRs. The TE671 AChR binds alpha Bgt, but is different from alpha Bgt-binding proteins in brain. Here we show that TE671 expresses the alpha-subunit mRNA coding for the muscle AChR, thereby proving that TE671 expresses a muscle-type AChR that is not expressed in adult brain. The isolated cDNA clones should prove useful for expression of large amounts of human muscle-type AChR alpha-subunit protein for studies of the autoimmune response to muscle AChRs in human myasthenia gravis. PMID- 3338556 TI - Vestiges of lost introns in the thermal stability map of DNA. AB - The absence of introns in prokaryotic genes has been explained by intron loss on various bases. Here we report another piece of evidence on intron loss, which was found in the thermal stability map of DNA. We calculated the local melting temperature of cDNA sequences and found that (i) gaps in thermal stability tend to occur near intron positions with a statistical significance, and (ii) one third of the gaps far from intron positions can be assigned to lost introns. From these results we conclude that the gaps of thermal stability in protein coding regions are the vestiges of lost introns. PMID- 3338557 TI - Separation of the pore-forming and cytotoxic activities from natural killer cell cytotoxic factor. AB - The influence of Ca2+ on the cytotoxic activity of natural killer cell cytotoxic factor (NKCF) was analyzed. When the natural killer susceptible cell line K562 was exposed to NKCF in the presence of 5 mM Ca2+, two peaks of cell damage were found. The first peak was observed after 30-40 min of incubation as a result of pore formation on the surface of target cells. The second was a peak of cytolytic activity which appeared after 24 h of incubation. Upon dilution of the NKCF preparation, only the first peak was observed. Therefore, NKCF produced by large granular lymphocytes in response to K562 consists of different proteins and represents pore-forming and cytolytic activities. PMID- 3338558 TI - Carboxyatractylate inhibits the uncoupling effect of free fatty acids. AB - The ATP/ADP-antiporter inhibitors and ADP decrease the palmitate-induced stimulation of the mitochondrial respiration in the controlled state. The degree of inhibition decreases in the order: carboxyatractylate greater than bongkrekic acid, palmitoyl-CoA, ADP greater than atractylate. GDP is ineffective. The inhibiting concentration of carboxyatractylate coincides with this arresting the state 3 respiration. Carboxyatractylate inhibition decreases when the palmitate concentration increases. Stimulation of controlled respiration by FCCP or gramicidin D at any concentration of these uncouplers is carboxyatractylate resistant, whereas that by low concentrations of DNP is partially suppressed by carboxyatractylate. These data together with observations that palmitate does not increase H+ conductance in bilayer phospholipid membranes and in cytochrome oxidase-asolectin proteoliposomes indicate that the ATP/ADP-antiporter is somehow involved in the uncoupling by low concentrations of fatty acids (or DNP), whereas that by FCCP and gramicidin D is due to their effect on the phospholipid bilayer. It is suggested that the antiporter facilitates translocation of palmitate anion across the mitochondrial membrane. PMID- 3338559 TI - 80% of muscarinic receptors expressed by the NB-OK 1 human neuroblastoma cell line show high affinity for pirenzepine and are comparable to rat hippocampus M1 receptors. AB - The NB-OK 1 human neuroblastoma cell line expressed muscarinic cholinergic receptors that could be labeled with N-[3H]methylscopolamine (a nonselective antagonist). 80% of these receptors showed high affinity for pirenzepine, i.e. belonged to the M 1 subtype found in neuronal tissues. Their binding properties were identical to those of rat hippocampus M 1 receptors, and differed from those of rat pancreas and heart muscarinic receptors. The remaining (20%) muscarinic receptors showed low affinity for pirenzepine and AF-DX 116, being therefore of an M2 beta (or B) subtype, and were similar to rat pancreatic receptors. PMID- 3338560 TI - Sequences both 5' and 3' to the transcription initiation site contribute to the ability of a mouse H-2 gene to respond to type I interferon. AB - To investigate the cis-acting DNA elements that are involved in the regulation of class I major histocompatibility complex genes by interferon, several promoter fragments of the H-2Kk gene were linked to the reporter chloramphenicol acetyl transferase (CAT) gene, and the CAT expression was analyzed in stable transfected cell lines. The functional activities of progressive deletions of the 5'-flanking region of the H-2Kk gene linked to the CAT gene have allowed us to define a discrete cis-acting DNA region necessary for interferon-mediated stimulation. Moreover, the H-2Kk gene transcribed by the nonregulated SV40 early promoter was also found to be under interferon regulation. Thus interferon enhancement of the H-2Kk gene expression appears to be mediated by two cis-acting elements, one located in the 5'-flanking region and the other by sequences downstream from the transcription initiation site. PMID- 3338562 TI - Further evidence for the presence of a thiazoline ring in the isoleucylcysteine dipeptide intermediate in bacitracin biosynthesis. AB - Isoleucylcysteine dipeptide, a first intermediate peptide in bacitracin biosynthesis, was liberated from the enzyme protein and oxidized with manganese dioxide in dimethylsulfoxide. The resulting oxidation product was identified by thin-layer chromatography as 2-(2-methyl-l-oxobutyl)-thiazole-4-carboxylic acid which has been isolated from the hydrolysate of bacitracin F. This result shows that the intermediate dipeptide contains a thiazoline ring, and that the thiazoline ring is synthesized at the dipeptide stage in the process of peptide chain elongation in bacitracin biosynthesis. Improbability of non-enzymatic dehydrative cyclization of the dipeptide is discussed. PMID- 3338561 TI - Tuftsin stimulates growth of HL60 cells. AB - Many functions of monocyte/macrophage and granulocyte are activated by tuftsin; principally phagocytosis, motility, immunogenic stimulation, antibacterial and antineoplastic activities. Here it is shown that tuftsin stimulates HL60 growth to twice the control rate. The uptake of [3H]uridine and [3H]leucine in a pulse of 30 min was also double that of the control. The uptake of thymidine was not stimulated. PMID- 3338563 TI - Involvement of a calcium-phospholipid-dependent protein kinase in the maturation of Xenopus laevis oocytes. AB - It has been described that phosphorylation, and dephosphorylation, of specific proteins is associated with key events of the cell cycle and is likely to be due to activation of kinase(s). From our results, the presence of calcium phospholipid-dependent protein kinase (PKC) was clearly demonstrated in both the cytosolic and particulate fractions of immature Xenopus laevis oocytes and in the cytosolic fraction of mature oocytes. However, it was less active in metaphase II than in prophase I-arrested oocytes. The enzyme was partially purified by DEAE cellulose and phenyl-Sepharose chromatography. It was activated in vitro by the tumor-promoting phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA) as already described for PKC from other tissues. On the other hand, a calcium phospholipid-independent histone kinase activity 4-fold higher in metaphase II- than in prophase I-arrested oocytes was detected. The possible role of PKC and phospholipid-independent histone kinase in the maturation process is discussed. PMID- 3338565 TI - Preformed PAF-acether and lyso PAF-acether are bound to blood lipoproteins. AB - PAF-acether (PAF) is a newly formed mediator not normally present in circulating blood. A compound exhibiting all of its biological characteristics but coeluting with phosphatidylcholine (PC) in high-pressure liquid chromatography (HPLC) was unveiled ('peak X') in normal human plasma. A second HPLC run of peak X HPLC fractions revealed the presence of PAF itself with concomitant disappearance of peak X. Beside PAF, immunoreactive apolipoproteins A-I and E were found in peak X. Also lipoproteins (Ls) purified using either ultracentrifugation or immunoaffinity chromatography yielded peak X and, in a second HPLC run, authentic PAF. L-free plasma was devoid of peak X. Finally, after preincubation with plasma, labeled PAF was found associated with Ls. Thus in human blood preformed PAF is bound in high amounts to Ls, a result of interest given the role of Ls and platelets in vascular diseases and the present knowledge on PAF biosynthesis. PMID- 3338564 TI - Methyllycaconitine and (+)-anatoxin-a differentiate between nicotinic receptors in vertebrate and invertebrate nervous systems. AB - Specific high-affinity binding sites for 125I-alpha-bungarotoxin and (-) [3H]nicotine have been measured in rat brain and locust (Schistocerca gregaria) ganglia. The binding sites for 125I-alpha-bungarotoxin had similar Kd values of 1.5 x 10(-9) and 0.8 x 10(-9) M for rat and locust preparations, respectively; the corresponding values for the (-)-[3H]nicotine-binding site were 9.3 x 10(-9) and 1.7 x 10(-7) M. Methyllycaconitine (MLA) potently inhibited 125I-alpha bungarotoxin binding in both rat and locust. MLA was a less effective inhibitor of (-)-[3H]nicotine binding whereas (+)-anatoxin-a was a very potent inhibitor at this site in the rat but not in the locust. These data suggest that (+)-anatoxin a is a useful probe for the high-affinity nicotine-binding receptor in vertebrate brain, whereas MLA is a preferential probe for the subclass of receptor that binds alpha-bungarotoxin. PMID- 3338567 TI - The turnover number for band 3-mediated sulfate transport in phosphatidylcholine bilayers. AB - The anion transport system of the human erythrocyte membrane was reconstituted in unilamellar phosphatidylcholine vesicles, and a vesicle subpopulation of a narrow size distribution was isolated from the sample by gel filtration. In this subpopulation, the turnover number of the transport protein (the band 3 protein) for sulfate transport was determined. It was found that, in the reconstituted system, the protein transports sulfate 5-10 times faster than in the human erythrocyte membrane. PMID- 3338566 TI - A two-dimensional NMR study of the antimicrobial peptide magainin 2. AB - Using two-dimensional NMR spectroscopy, a complete 1H resonance assignment has been obtained for the peptide magainin 2 recently isolated from Xenopus laevis. It is demonstrated that this peptide adopts an alpha-helical structure with amphiphilic character when dissolved in a mixture of trifluoroethanol (TFE) and H2O. The transition to the alpha-helical conformation occurs at very low concentrations of TFE. PMID- 3338568 TI - cDNA clones completing the nucleotide and derived amino acid sequence of the alpha 1 chain of basement membrane (type IV) collagen from mouse. AB - Six cDNA clones add 3549 nucleotides to the DNA sequence of the alpha 1 chain of basement membrane (type IV) collagen. Thus the complete nucleotide and derived amino acid sequence of the alpha 1 type IV collagen with 5007 nucleotides coding for 1669 amino acids with a calculated Mr of 160,827 is known. The six cDNA clones cover the putative N-terminal signal peptide, the 7 S region and two thirds of the helical region extending into the previously published murine nucleotide sequence [(1986) Gene 43, 301]. The protein sequence for 289 amino acids of the helical region adjacent to the 7 S region has not previously been published for any species. PMID- 3338570 TI - Variable RNA polymerase populations in the life cycle of Trypanosoma brucei. AB - DNA-dependent RNA polymerase from blood forms and culture forms of the parasitic protozoan Trypanosoma brucei was resolved into multiple peaks of activity by DEAE Sephadex chromatography. The enzyme from the two forms was found to be different by several criteria, suggesting that it is subject to developmental control. PMID- 3338569 TI - Membrane action of synthetic N-terminal peptides of influenza virus hemagglutinin and its mutants. AB - Synthetic peptides corresponding to the N-terminal of the cleaved hemagglutinin (HA2) of influenza virus induce an increase in conductance of planar phospholipid bilayers, and cause the release of encapsulated molecules from large unilamellar liposomes. Two mutant peptides, derived from hemagglutinins of mutant viruses with no or reduced fusion activity, do not alter the membrane conductance significantly. These observations support the hypothesis that influenza virus fuses with its target membrane by inserting the HA2 N-terminal into the membrane. PMID- 3338571 TI - Enzymic properties of intestinal aminopeptidase P: a new continuous assay. AB - A continuous photometric assay of aminopeptidase P activity was developed which is based on a coupled enzymic assay with the substrate Gly-Pro-Pro-pNA and DPP IV as auxiliary enzyme. This assay was used to evaluate the kinetic parameters and inhibitory profile of intestinal brush border aminopeptidase P. PMID- 3338572 TI - The effect of inhibition of cholesterol esterification on the fate of cholesterol derived from HDL in rat hepatocyte monolayers. AB - Rat HDL2 is known to stimulate bile acid synthesis in rat hepatocyte monolayers. The intracellular fate of the cholesterol derived from the HDL2 was studied using the inhibitor of cholesterol esterification, Sandoz compound 58-035. Rat HDL2 added to rat hepatocyte monolayers caused a stimulation of cholesterol esterification of 32%. This stimulation could be inhibited by 58-035. A small significant increase in bile acid synthesis was also observed in cells in the presence of HDL2, confirming our earlier observations. 58-035 prevented this increase. These observations imply that cholesterol entering the cell from HDL2 is first esterified and can only enter the substrate pool for bile acid synthesis after subsequent intracellular hydrolysis. PMID- 3338573 TI - High incorporation of dietary 1-O-heptadecyl glycerol into tissue plasmalogens of young rats. AB - When 1-O-heptadecyl-rac-glycerol was fed (20 mg/g of food) to 19-day-old rats for 10 days, a high incorporation of the heptadecyl group into the 1-O-alk-1'-enyl group of ethanolamine plasmalogens of all tissues was observed. For example, 62% of the alkenyl groups from liver plasmalogen was of the 17:0 variety. The analogous values for other tissues were 62% in kidney, 57% in lung, 57% in heart, 50% in intestine, 43% in erythrocytes, 25% in testis and 8% in brain. The corresponding figures in the control rats (fed normal rat chow) were only 2-3% of 17:0 for all tissues. Available evidence indicates that dietary 1-O-heptadecyl-sn glycerol is utilized to form tissue plasmalogens without the cleavage of the ether bond. The relevance of these results to the possible dietary ether lipid therapy of patients suffering from congenital ether lipid deficiency is discussed. PMID- 3338574 TI - Occurrence of glucose polymer in undifferentiated PC12 cells. AB - A large glucose polymer was found, following pronase digestion, in PC12 pheochromocytoma cells metabolically labeled with [1-3H]galactose. The polymer was excluded from a Bio-Gel A-0.5 m column and adsorbed by immobilized concanavalin A-Sepharose from which it was eluted with 10 mM alpha methylmannoside. Glucose was found to be the sole component monosaccharide. Except for those capable of degrading glycogen, no exo- or endo-glycosidases cleaved the polymer. This is the first report on the occurrence of a glucose polymer in undifferentiated PC12 cells. PMID- 3338575 TI - Towards an understanding of the biological function of histone acetylation. AB - A model is presented which explains the biological function of posttranslational acetylation of core histones in chromatin. Along the lines of this model histone acetylation serves as a general mechanism to destabilize nucleosome core particles during various processes occurring in chromatin. Acetylation acts as a signal that modulates histone-protein and histone-DNA interactions and finally leads to the displacement of particular histones from nucleosome cores. The high specificity of the acetylation signal for different processes (DNA replication, transcription, differentiation-specific histone replacement) is achieved by site specificity and asymmetry of acetylation in nucleosomes. The essential features of this model are in accord with the more recent results on histone acetylation. PMID- 3338576 TI - Absence of 7-acetyl taxol binding to unassembled brain tubulin. AB - The effect of taxol on microtubule proteins at 0 degrees C is controversial. In order to determine if taxol is unable to bind to unassembled tubulin, as has been hypothesized, the binding of [3H]acetyl taxol has been studied using equilibrium microdialysis. Ac-taxol bound to microtubules at 37 degrees C and the binding remained stable when the temperature was lowered to 0 degrees C. Ac-taxol bound also at 0 degrees C to microtubules stabilized with rhazinilam. In contrast, there was no binding of Ac-taxol to unassembled tubulin, either free tubulin at 0 degrees C or tubulin, complexed with several microtubule poisons, at 0 and 37 degrees C. PMID- 3338577 TI - A.I.D. and AIDS--too close for comfort. PMID- 3338578 TI - Revised new guidelines for the use of semen-donor insemination. The American Fertility Society. PMID- 3338579 TI - Early pregnancy wastage: relationship between chorionic vascularization and embryonic development. AB - The chorionic villous vascularization of 40 patients with first trimester spontaneous abortion was compared with that of 10 patients undergoing legal abortion (control group). The spontaneous abortion group was subdivided into a group with intrauterine embryonic death (n = 20) and a group with blighted ova (n = 20). Villous vascularization appeared unaffected after prolonged postmortem intrauterine retention. The incidence of vascularized villi was 89% in the control group, 26% in the group with embryonic death, and 9% in the group with blighted ova. In addition, the vascular density of vascularized villi was three to four times higher in the control group than in the two spontaneous abortion groups. The present study provides evidence that, in case of embryonic death and blighted ova, chorionic villous vascularization is deficient. PMID- 3338580 TI - The inhibitory effects of danazol, danazol metabolites, gestrinone, and testosterone on the growth of human endometrial cells in vitro. AB - Danazol and gestrinone are effective drugs in the treatment of endometriosis. Their mechanism of action remains uncertain, but may be related to their androgenic activity. The authors examined the effect of danazol on human endometrial cells cultured in vitro, its two major metabolites, ethisterone and 2 hydroxymethyl ethisterone, gestrinone, and testosterone (T) at 1X and 10X expected plasma concentrations. Danazol and T suppressed growth by 20.8 and 25.0% (P less than 0.01), respectively, at the lower dose, and by 26.9 and 35.5% (P less than 0.01), respectively, at the 10-fold higher dose. No significant suppression of growth occurred with gestrinone, ethisterone, or 2 hydroxymethyl ethisterone. The results provide further evidence that danazol and T (but not gestrinone) may act by a direct effect on endometrial tissue. PMID- 3338582 TI - An investigation of the relationship between emotional maladjustment and infertility. AB - The purpose of this investigation was to examine the psychologic test results of women diagnosed with infertility as compared with the general population of women. The infertile group consisted of 150 women, whereas the control group included 50 women. Both groups were similar in regard to age and number of years married. The tests administered were: the 16 Personality Factor, the IPAT Anxiety Scale, the IPAT Depression Scale, the Tennessee Self-Concept Scale, and the Internal-External Scale (locus of control). Scores on a total of 41 test variables did not differ significantly between the two groups. In fact, the means and standard deviations for all variables were remarkably similar. This study concludes that significant emotional maladjustment is no more prevalent in women coping with infertility than for the general population of women. Results from this investigation cast doubt on the historical assumption that stress may be a causal factor in infertility. PMID- 3338581 TI - Biologic effects of equilin sulfate in postmenopausal women. AB - In order to determine the relative potency of equilin sulfate (EqS), a major constituent of conjugated equine estrogens, 15 women received oral doses of EqS (0.15, 0.31, and 0.625 mg) for 25 days. Doses of 0.31 and 0.625 mg significantly stimulated hepatic globulins. This stimulatory effect ranged from being 1.5 to 8 times greater than the effects of comparable doses of estrone sulfate and conjugated equine estrogens. A significant stimulation in high-density lipoprotein-cholesterol occurred with as little as 0.15 mg of EqS. Elevations in the high-density lipoprotein/low-density lipoprotein-cholesterol ratio occurred with EqS, which resulted in an approximately 4-fold greater response than that achieved with comparable doses of conjugated equine estrogens. The fasting urinary calcium/creatinine ratio was only significantly lowered with 0.625 mg of EqS and was less potent than conjugated equine estrogens in this regard. It is concluded that EqS is a potent estrogen that contributes significantly to the hepatic stimulatory effects of conjugated equine estrogens. These data also provide support for the suggestion that there may be a dissociation in potency between estrogenic effects on liver and bone. PMID- 3338583 TI - In vitro fertilization in women with "frozen pelvis": clinical outcome of treatment. AB - The outcome of 93 consecutive cycles of in vitro fertilization (IVF) and embryo transfer (ET) treatment in 52 women with "frozen pelvis" is reported. The treatment termination rate due to inadequate ovarian stimulation was 20%. The mean +/- standard deviation of the number of follicles of mean diameter greater than or equal to 15 mm, oocytes recovered and fertilized per operation, and embryos replaced per cycle were 4.80 +/- 2.07, 4.02 +/- 2.32, 2.54 +/- 2.06, and 2.57 +/- 1.30, respectively. The pregnancy rate per ET was 29.6%. These data compare with those of other treated women with adhesion-free ovaries over the same period, suggesting that pelvic adhesive disease has no adverse effect on outcome of IVF-ET. PMID- 3338584 TI - The use of in vitro fertilization to evaluate putative tests of human sperm function. AB - Results of 106 in vitro fertilization procedures were used to evaluate the usefulness of tests of human sperm function for predicting fertilization rates. Sperm tests included concentration, motility, morphology, vitality (eosin Y exclusion), nuclear immaturity (aniline blue stain), and hypo-osmotic swelling. Only the number of sperm in the insemination medium, percentage normal morphology, and vitality were statistically significant in logistic regression models of fertilization rates. The other tests, such as the hypo-osmotic swelling test, did not give additional information about fertilization rates in this study. It is concluded that logistic regression analysis of factors affecting results of fertilization in vitro provides a powerful tool for evaluating some clinical tests of sperm function. PMID- 3338586 TI - The effects of clomiphene citrate on the histology of human endometrium in regularly cycling women undergoing in vitro fertilization. AB - Thirty-six women with histories of regular cycles undergoing elective laparoscopic sterilization volunteered to participate in a research program of endometrial biopsy, oocyte donation, and in vitro fertilization (IVF). One half of the volunteers received 5 days of 150 mg of clomiphene citrate (CC) ending 5 days before human chorionic gonadotropin injection and 6.5 days before laparoscopy and biopsy. The control patients were treated identically, except they received no CC. CC cycles were more uniform in duration and follicular response better, enabling a prescheduled IVF regimen. Control cycles were complicated by poor follicular response or untimely endogenous surges of luteinizing hormone (LH). The mean urinary estrone glucuronide excretion per follicle was the same in each group, and there was no evidence of a luteal defect by either luteal phase length or urinary pregnanediol excretion. Although there were minor differences in mitotic rate and basal vacuolation of glandular epithelium in biopsies, no specific deleterious effect of CC could be seen. PMID- 3338585 TI - Cryopreservation of zygotes and early cleaved human embryos. AB - Zygotes and 2- to 5-cell human embryos were frozen in 1,2-propanediol and sucrose; results of the first 50 cycles (45 patients) are presented. A total of 41 zygotes (17 attempts at thawing) were thawed, resulting in six singleton clinical pregnancies (15% per embryo; 35% per cycle), of which three delivered, one aborted, and two are ongoing. Fifty-seven cleaved embryos were thawed in 33 other cycles, resulting in four singleton and one twin pregnancy (11% per embryo; 15% per cycle), of which four delivered and one is ongoing. Depending on the cell stage, 61% to 81% of embryos survived cryostorage, but 2-cell embryos did not implant. One fifth of cryoinjury was due to the formation of cracks in the zona pellucida. The incidence of implantation was not enhanced when more than one freeze/thawed embryo was replaced, most pregnancies being obtained from single embryo replacements. At least 8% more births are expected in addition to conventional in vitro fertilization methods when the current policy of replacing three fresh embryos and freezing the remainder using this technique is applied. This method will result in two to four times more pregnancies per spare embryo, compared with other cryopreservation methods using older embryos. PMID- 3338587 TI - Male infertility associated with round-headed acrosomeless spermatozoa. AB - The properties of spermatozoa with round head syndrome in four unrelated patients are reported. The findings were as follows: (1) Electron microscopy demonstrated that all spermatozoa lacked an acrosome and postacrosomal sheath. (2) Acrosin activity was only 1% to 6% of that found in sperm obtained from fertile donors. (3) Phospholipase A2 activity was not significantly different from that of spermatozoa from donors of unknown fertility. (4) Electrophoresis of whole sperm extracts revealed deficiencies in major protein bands. (5) The round-headed spermatozoa failed to bind or penetrate the vitellus in the egg penetration test. (6) The rates of chemically induced nuclear chromatin decondensation of round headed spermatozoa suggest that the acrosome content is not involved in this process. PMID- 3338588 TI - Effect of prostaglandins on human sperm function in vitro and seminal adenosine triphosphate content. AB - The aim of the present study was to evaluate the effect of addition of physiologic amounts of different prostaglandins normally present in semen, on sperm motility, on sperm penetration capacity in cervical mucus in vitro, and on the adenosine triphosphate (ATP) concentration in semen. Semen samples were obtained from volunteers who were attending the fertility outpatient clinic. Sperm motility was measured on a video recorder with a built-in timer, sperm penetration by the Kremer test, and ATP by bioluminescence assay. The addition of 19-hydroxy prostaglandin (PG) E to ejaculates positively stimulated sperm motility and sperm penetration capacity. The opposite effect was observed with 19 hydroxy PGF. PGE1, PGE2, and PGF2 alpha had no effect on either parameter, while PGF1 alpha reduced the sperm motility. The addition of 19-hydroxy PGE to ejaculates increased and the addition of 19-hydroxy PGF reduced semen concentrations of ATP. However, only the last-mentioned effect was statistically significant (P less than 0.05). It is suggested that, in particular, 19-hydroxy PGE and 19-hydroxy PGF are important regulators of sperm motility and that the effect may be mediated via effects on the ATP content in the spermatozoa. PMID- 3338589 TI - The human sperm-hamster egg penetration assay: prognostic value. AB - Males from 227 infertile couples were evaluated using the human sperm-hamster egg penetration assay (SPA). Indications for the SPA were abnormal semen analyses, poor postcoital tests, documented autologous sperm antibodies, and long-term unexplained infertility. Normal results defined as greater than or equal to 11% penetration were seen in 58.6% of couples. Penetration rates of 1% to 10% were observed in 25.6%, and 15.9% failed to penetrate any of the oocytes. During the follow-up period, with a mean of 17.9 months, 26.9% conceived at least once with or without treatment. Monthly fecundity was 0.014 for normal SPA patients and 0.007 for the abnormal SPA group when calculated by the Kaplan-Meier survival curve with Cox correction for unequal follow-up. The monthly fecundity rate at any time during the 30-month interval of follow-up was twice as great for men with normal SPA values as for those with abnormal values, regardless of male or female diagnosis or therapy indicating the prognostic value of the SPA in an infertile population. PMID- 3338590 TI - Immunocytochemistry of the estrogen receptor in spontaneous endometriosis in rhesus macaques. AB - Immunocytochemical, biochemical, and histologic analysis of endometriotic lesions and endometria from rhesus macaques with endometriosis revealed several distinctions between ectopic and eutopic endometrium. In lesions, unlike endometrium, neither the mean percentages of estrogen receptor positive (ER+) cells nor the total ER content changed significantly during the menstrual cycle. In eutopic endometria, ER staining in both stromal and epithelial cells increased and decreased synchronously during the cycle, but in endometriotic lesions, such synchrony was lacking. Moreover, in lesions, unlike endometria, the percentage of ER+ cells was low in the stroma and highly variable in epithelium throughout the cycle. These data, taken together, indicate a defect in the hormonal regulation of ER in endometriotic lesions of monkeys. PMID- 3338591 TI - Identification of two species of suppressive factor of differing molecular weight released by in vitro fertilized human oocytes. AB - Preimplantation human embryos have been shown to release factors that have immunosuppressive activity and that are highly correlated with successful implantation. The present study was undertaken to determine the molecular weight of these factors using HPLC. Two peaks of suppressive activity were found associated with molecular weights of 3.7 +/- 0.3 and 1.2 +/- 0.1 kd, respectively. The potential significance of low molecular weight immunosuppressor factors in avoiding maternal inflammatory and immunologic responses is discussed. PMID- 3338592 TI - Insensitive ovary syndrome with a unique process of follicular degeneration. PMID- 3338593 TI - Pregnancy caused by sperm from vasa efferentia. PMID- 3338594 TI - The effect of hysterectomy on the age at ovarian failure. PMID- 3338595 TI - Open-ended vasectomy. PMID- 3338596 TI - AIH after induction of multiple ovulation. PMID- 3338598 TI - A new year look at constitutional rights of public employees. PMID- 3338597 TI - Wanted: nursing advocates for children with AIDS. PMID- 3338599 TI - Are nailfold capillary changes indicators of organ involvement in progressive systemic sclerosis? AB - Nailfold capillary abnormalities in 40 patients suffering from progressive systemic sclerosis (scleroderma; PSS) were studied by widefield nailfold capillary microscopy. Capillary enlargement and loss were graded using the rating scales of Maricq and Minkin. Capillary changes were correlated with organ involvement and immunological abnormalities. A high correlation was found between the grade of nailfold capillary changes and the clinical severity of PSS. Nailfold capillary microscopy seems to be a useful method to get quick information in order to predict organ involvement in PSS. PMID- 3338601 TI - Reiter's syndrome and human immunodeficiency virus infection. AB - A 35-year-old Black male with a long history of intravenous drug abuse developed clinical manifestations of Reiter's syndrome, with significant joint and psoriasiform skin involvement. In addition, he had signs and symptoms compatible with human immunodeficiency virus (HIV) infection and had a positive HIV antibody test confirmed with Western blot testing. Although many dermatologic manifestations of HIV infection have been described, this is the first time that an association with Reiter's syndrome has been reported. Recently, the development of psoriasis in other patients with HIV infection has been described. Taken together, these occurrences suggest that the purported retroviral relationship with psoriasis and related dermatoses may warrant further examination. PMID- 3338600 TI - Self-healing epitheliomata of Ferguson-Smith: cytogenetic and histological studies, and the therapeutic effect of etretinate. AB - 212 epitheliomata developed in two unrelated women with self-healing epitheliomata of Ferguson-Smith. Most of the lesions appear on the face, often in crops; they enlarge over 4 weeks and, without treatment, resolve over 4 months to leave a ragged scar. One of the patients developed an unusual syringoma, a papillary carcinoma of the thyroid and a mucosal squamous cell carcinoma which failed to involute spontaneously. Cytogenetic studies did not reveal any abnormality of DNA repair. Surgical excision of the epitheliomata is successful but time consuming. X-irradiation should not be used, but cryotherapy of early lesions is helpful. One patient, treated with etretinate for 24 months, has developed only 8 epitheliomata over this time, compared with 23 in the previous 24 months. Etretinate therefore appears to prevent new lesions from developing. PMID- 3338602 TI - Fibrous hamartoma of infancy--infantile subcutaneous myofibroblastoma. AB - This paper presents light and electron microscopic findings in a case of fibrous hamartoma of infancy. Histological examination revealed different tissue components: irregular trabecular collagen fibers among mature adipose tissue, and mesenchymal cells at the border of fibrocollagenous trabeculae as well as around blood vessels. Ultrastructurally most of the tumor cells represented myofibroblasts. According to the predominance of a distinct cell type, fibrous hamartoma of infancy cannot be regarded as a hamartomatous lesion but should be included in the group of juvenile fibromatoses under the term 'infantile subcutaneous myofibroblastoma'. PMID- 3338603 TI - Sudan-IV-positive material of the nail plate related to plasma triglycerides. PMID- 3338604 TI - Second pregnancy with spontaneous ovulation following clomiphene- or gonadotropin induced pregnancy. AB - For investigation of the rates of spontaneous pregnancy following termination of pregnancy induced by treatment with clomiphene or human menopausal gonadotropin human chorionic gonadotropin (hMG-hCG) and of spontaneous abortion in the second pregnancy, 119 women (58 with an anovulatory cycle and 141 with amenorrhea) who desired another pregnancy were studied. The rate of spontaneous pregnancy following pregnancy induced by clomiphene was 46.6%, which was significantly (p less than 0.001) higher than that following pregnancy induced by hMG (14.9%). The mean (+/- SEM) period between the termination of the first induced-ovulation pregnancy and the second spontaneous pregnancy was 16.6 +/- 1.4 months. The spontaneous abortion rates in the second pregnancies after pregnancies induced by clomiphene and hMG were 7.5% and 9.8%, respectively, which were significantly (p less than 0.001, p less than 0.05) lower than those in the first pregnancy (25.7%, 33.0%). There was no difference between the spontaneous abortion rates following a first pregnancy which terminated in abortion and those following a pregnancy which ended in birth. These data suggest that a first pregnancy in anovulatory women may restore the ovulatory cycle and have a beneficial effect on the rates of spontaneous abortion in the second pregnancy. PMID- 3338605 TI - The influence of maternal exercise on the uteroplacental vascular bed resistance and the fetal heart rate during normal pregnancy. AB - The effects of maternal exercise were studied in 20 healthy women with uncomplicated pregnancies. A continuous-wave Doppler ultrasound system was used to record arterial flow velocity waveforms from the ascending vasculature downstream from the uterine artery. The fetal heart rate was monitored with a Doppler ultrasound cardiotocograph. No significant change was found in the uterine blood flow velocity waveform post-exercise, as expressed by the pulsatility index, suggesting absence of change in the uterine vascular bed resistance. The fetal heart rate significantly increased after exercise. PMID- 3338606 TI - Long-term ailments due to anal sphincter rupture caused by delivery--a hidden problem. AB - Questionnaires concerning ailments were sent postpartum (mean two years) to 62 women with anal sphincter ruptures (ASR), who were compared with a matched control population. The frequency of anal sphincter rupture at the hospital during delivery in the period, 1978-82, was 0.7% (n = 63). Primiparity, instrumental deliveries, abnormal presentation, large babies and oxytocin stimulation were all risk factors. Of 59 women answering the questionnaire 37 (63%) stated that they had had ailments three months postpartum, mainly with pain and involuntary passage of flatus but also with dyspareunia and occasional incontinence of faeces. Long-term symptoms were noted by 28 (48%) of the women, mainly with involuntary passage of flatus but also perineal pain, dyspareunia and occasional incontinence of faeces. Long-term symptoms occurred in 7 (88%) of women with ASR also involving the anal mucosa, but only in 21 (39%) of those with ASR only. Three of the patients subsequently underwent reconstructive surgery, and three complained of psychological problems. PMID- 3338607 TI - Clinical aspects in the surgical treatment of varicocele in subfertile men. I. Comparison of observed and expected pregnancy rates. AB - Ninety-six couples, consulting for primary (n = 73) or secondary (n = 23) infertility, and thought to be infertile due to a varicocele in the husband associated with sperm abnormalities, were subjected to a follow-up study. Of these, 57 were surgically corrected and 39 were not, depending only on the patient's choice. All women were intensively treated where necessary. From our data we conclude that (1) fertility prognosis is significantly better in couples with secondary subfertility than in couples with primary subfertility, (2) surgical correction of varicocele in cases of secondary subfertility does not increase subsequent pregnancy rates, and (3) surgical correction of varicocele in cases of primary subfertility significantly increases subsequent pregnancy rates, since cumulative observed pregnancy rates are more than double the cumulative theoretically expected treatment-independent pregnancy rates. PMID- 3338608 TI - Clinical aspects in the surgical treatment of varicocele in subfertile men. II. The role of the epididymal factor. AB - Ninety-six couples, consulting for primary (n = 73) or secondary (n = 23) infertility, and thought to be infertile due to a varicocele in the husband associated with sperm abnormalities, were subjected to a follow-up study. Of these, 57 were surgically corrected and 39 were not, depending only on the patient's choice. All women were intensively treated where necessary. All patients who were corrected were subjected to scrotal exploration in a search for epididymal anomalies. From our data we conclude that (1) on a statistical basis, comparing observed with expected pregnancy rates, varicocelectomy is useful in primary infertility and unnecessary in secondary infertility and (2) on an individual basis, patients with primary infertility and 'pure' varicoceles have a better prognosis than patients with concomitant epididymal dysfunction. PMID- 3338609 TI - Symptomatology of ovarian cancer. AB - The symptomatology of ovarian cancer was retrospectively reviewed in 362 patients. According to the stage at diagnosis, the disease was classified as early (stages IA-IIA) or advanced (stages IIB-IV). The most common initial symptoms were abdominal swelling and/or palpable tumour, pain and gastro intestinal symptoms. The initial symptoms, however, were not necessarily those that prompted the patients to seek medical advice. Most were first seen by a gynecologist, which possibly explains the shortness of doctor's delay in the urbanized catchment region. PMID- 3338610 TI - A comparison of AmnioStat-FLM with three established methods of assessing fetal lung maturity. AB - A new rapid test of fetal lung maturity (the AmnioStat-FLM) was compared with two currently available rapid tests and with 2-dimensional thin-layer chromatography (2-d TLC). Forty-nine specimens of liquor obtained within 72 h of delivery were assessed, 27 of which were contaminated with blood or meconium. The AmnioStat-FLM compared well with spectrophotometry, the shake test and with 2-d TLC. Only the Amniostat-FLM and the 2-d TLC were reliable in the presence of contamination. The results suggest that the AmnioStat-FLM is a reliable, rapid test and unaffected by the presence of contamination. PMID- 3338611 TI - Unconjugated 17 beta-oestradiol and oestriol in maternal serum and in cord vein and artery blood at term and preterm delivery. AB - The serum level of unconjugated 17 beta-oestradiol (E2) and oestriol (E3) in the maternal vein (MV), the umbilical vein (UV) and artery (UA) immediately after term (n = 34) and preterm (n = 74) labour was measured to clarify the hormonal changes that occur between the maternal and fetal compartments. The following results were found. (1) The level of E2 and E3 increased equally in the MV, UV and UA serum from the 28th-32nd week to the 33rd-36th week of pregnancy. From the 33rd-36th week to the 40th week there was no change in the MV, but the value of E2 and E3 decreased significantly in the UV and UA serum. (2) The serum level of E2 in the MV was significantly higher than that in the UV and UA during every gestational period. In contrast, the serum concentration of E3 in the MV was significantly lower than that in the UV and UA. (3) The value of 'UA/UV X 100' of E2 and E3 was about 30% during the 28th-40th week. (4) A weak correlation was found between the MV serum level of E2 and E3 and UA serum concentrations. A strong correlation was found between the UV and UA serum levels of E2 and E3. The authors suggest that though there is a close connection between the fetal and the maternal organism, the fetus is still capable of maintaining its hormonal environment independently. PMID- 3338612 TI - Pulmonary and placental 15-hydroxyprostaglandin dehydrogenase in rat during pregnancy. AB - 15-Hydroxyprostaglandin dehydrogenase (PGDH) in rat lung and placenta during pregnancy was examined using a photometric assay. Pulmonary PGDH activity varied slightly during pregnancy, being significantly higher on days 10 and 19 of gestation than on day 22. Placental PGDH activity changed strikingly according to the day of pregnancy. Activity was relatively high on day 10 of gestation, fell to a low level on day 15, then increased to a maximum on day 22. A rapid fall in pulmonary PGDH activity and a remarkable increase of placental PGDH activity occurred on the day just before parturition. The results suggest that pulmonary and placental PGDH activity may cooperatively contribute to the continuity of pregnancy, and the process of parturition. PMID- 3338613 TI - The effect of chronic methadone treatment on intra-uterine growth of the cynomolgus monkey (Macaca fascicularis). AB - A generally accepted management of heroin addiction during pregnancy is treatment with methadone, which reduces the complications of heroin addiction considerably. Reports in the literature are still contradictory, however, about the influence of methadone upon birthweight. In pregnant Cynomolgus monkeys (Macaca fascicularis) the effect of chronic treatment with rather high dosages of methadone upon birthweight was studied under standardized conditions. Birthweights were significantly lower in the methadone-treated animals. PMID- 3338614 TI - Contact-independent polarization of the cell surface and cortex of free sea urchin blastomeres. AB - In a normal, intact sea urchin embryo blastomeres are structurally polarized so that all microvilli and cortical "pigment granules" are situated at the apical surfaces facing the hyaline layer and are absent from basolateral surfaces facing adjacent blastomeres and the internal embryonic cavity. To test the roles of intercellular contacts and the hyaline layer in the process of establishing this blastomere polarity, these two factors were experimentally eliminated; sea urchin eggs of four species were denuded of the nascent hyaline layer soon after fertilization and then cultured in calcium-free artificial seawater to prevent subsequent intercellular adhesion and contact. Such free blastomeres divided normally and still developed polarized distributions of microvilli and pigment granules resembling those of the corresponding blastomeres in intact embryos. These results indicate that the process of polarization is intrinsic to individual blastomeres (self-polarization) and that neither intercellular contacts nor adhesion of microvilli to the hyaline layer is necessary. The precise temporal and spatial coincidence of the patterns of polarization and the division cycles further suggests that a mechanistic link is maintained among cell division, blastomere polarization, and probably also a heritable component of the animal-vegetal axis. PMID- 3338615 TI - In vitro neurite extension by granule neurons is dependent upon astroglial derived fibroblast growth factor. AB - When grown in the absence of astroglial cells, purified mouse cerebellar granule neurons survive less than 36 hr and do not extend neurites. Here we report that low concentrations of basic fibroblast growth factor (bFGF, 1-25 ng/ml) maintained the viability and promoted the differentiation of purified granule neurons. The effect of bFGF on granule cell neurite outgrowth was dose dependent. Neurite outgrowth was stimulated markedly in the presence of 1-25 ng/ml bFGF, but effects were not seen below 1 ng/ml or above 50 ng/ml. When affinity-purified antibodies against bFGF (1-5 micrograms/ml) were added either to purified granule cells or to co-cultures of neurons and astroglial cells, process extension by granule neurons was severely impaired. The inhibition of neurite outgrowth in the presence of anti-bFGF antibodies was reversed by the addition of 25 ng/ml of exogenous bFGF. In addition to neuronotrophic effects, bFGF influenced the rate of growth of the astroglial cells. This result depended on whether the astroglia were grown in isolation from neurons, where low doses of bFGF (10-25 ng) stimulated glial growth, or in coculture with neurons, where much higher doses of bFGF (100-250 ng/ml) were needed for glial mitogenesis. Immunoprecipitation of lysates from 35S-labeled cerebellar astroglial cells with anti-bFGF antibodies revealed a single band after SDS-PAGE at 18,000 Da, the molecular weight of bFGF. These results indicate that glial cells synthesize bFGF and are possibly an endogenous source of bFGF in cerebellar cultures. Thus, astroglial cells synthesize soluble factors needed for neuronal differentiation. PMID- 3338616 TI - Developmental origin of segmental differences in the leech ectoderm: survival and differentiation of the distal tubule cell is determined by the host segment. AB - The body plan of the adult leech is metameric, with each hemisegmental complement of ectodermal and mesodermal tissues being produced from a set of seven serially repeated embryonic blast cells. Previous studies have shown that homologous o blast cells give rise to an almost identical complement of descendant cells in each of the 21 abdominal segments, but that one o blast cell derivative--the distalmost cell of the nephridial tubule--is only present in 15 abdominal segments in the mature leech. Here we show that all o blast cells generate a presumptive distal tubule cell and that this cell migrates to its normal position in all abdominal segments. However, in segments which normally do not contain the mesodermal portion of the nephridium, the distal tubule cell dies before undergoing its terminal morphological differentiation. To ascertain whether the fate of the distal tubule cell is determined by its lineage history or by the segmental environment into which it is born, we utilized a previously described procedure for altering the segmental register between different embryonic cell lines. This procedure allowed us to effectively transplant o blast cells into more posterior segments prior to the cell divisions which generate their descendant clones. The results indicate that the survival or death of the distal tubule cell is determined by the identity of the host segment and that a given distal tubule cell could be effectively murdered or rescued by slipping its blast cell precursor into an appropriate segment. These findings suggest that the segment-specific pattern of distal tubule cell survival is not inherent to the O cell line, but arises from interactions with surrounding tissues. PMID- 3338617 TI - Developmental discord among markers for cholinergic differentiation: in vitro time courses for early expression and responses to skeletal muscle extract. AB - The effects of skeletal muscle extract on the development of CAT, ACh synthesis, high affinity choline uptake, and AChE activities were studied in dissociated ventral spinal cord cultures prepared from 14-day gestational rat embryos. In the absence of muscle extract, the development of CAT and AChE follow biphasic time courses in which they show initial declines followed by periods of steadily increasing activity. In contrast, ACh synthesis and high affinity choline uptake both gradually increase throughout the entire culture period. The presence of muscle extract both prevents the initial decline of CAT and AChE as well as stimulates the rates of development of all four cholinergic markers; however, the degrees and time courses of stimulation differ markedly. The effects of muscle extract on the kinetic and pharmacological properties of ACh synthesis and choline uptake in rat ventral cord cultures were also investigated. Cells treated with muscle extract for 2 days express both high affinity (Km = 1.6 microM) and low affinity (Km = 22 microM) choline uptake mechanisms. Control cells, on the other hand, express only low affinity uptake at this stage but develop a high affinity uptake mechanism by Day 7. During this time both ACh synthesis and high affinity choline uptake become increasingly sensitive to inhibition by hemicholinium-3. These results demonstrate that skeletal muscle factors enhance the development of cholinergic properties in embryonic spinal cord cultures. However, differences in sensitivity to muscle extract concentration, time courses of development, and degrees of stimulation suggest that these changes may involve distinct cellular mechanisms which are differentially affected by skeletal muscle factors. PMID- 3338618 TI - Localization of actin networks during early development of Tubifex embryos. AB - In precleavage zygotes of Tubifex, actin filaments segregate to the animal and vegetal poles forming the polar actin filament networks (AFNs). In this study, the fate of the polar AFNs during early development of Tubifex embryos has been followed using rhodamine-phalloidin as a specific stain for F-actin. During the first two cleavages, which are unequal and meridional, the polar AFNs are retained at the regions of cells corresponding to the poles of the precleavage zygote; thereby, they are segregated to the CD-cell at the 2-cell stage then to the D-cell at the 4-cell stage. As the mitotic apparatus forms in the D-cell, however, the vegetal polar AFN translocates toward the animal pole of the cell where the mitotic apparatus is located and unites with the animal polar AFN there. This redistribution of the AFNs is impaired by colchicine treatment, suggesting the involvement of microtubules. Thereafter, the unified AFN is found to be associated with nuclear regions of the macromeres of the D-cell line, and finally partitioned to the teloblast precursors 2d and 4d and an endodermal cell 4D. Cytochalasin B experiments indicate that the AFNs play a cytoskeletal role in generating and maintaining the spatial organization of the cytoplasm which gives rise to the intracellular localization of the cytoplasm and the mitotic apparatus orientations. The developmental and cellular significance of the AFNs is discussed in relation to the localization of developmental potential and the regulation of the mitotic apparatus organization in the Tubifex embryo. PMID- 3338619 TI - Accumulation of components of basal laminae: association with the failure of neural crest cells to colonize the presumptive aganglionic bowel of ls/ls mutant mice. AB - Aganglionosis occurs in the terminal colon of the ls/ls mouse because an intrinsic defect of the presumptive aganglionic tissue prevents the entry and colonization of this portion of the bowel by migrating neural crest cells. The current study was undertaken to determine if abnormalities of the extracellular matrix could be identified in this segment that might account for migratory failure. Since basal laminae of the muscularis mucosa are overproduced in the aganglionic segment of adult ls/ls mice, we examined components of basal laminae in fetal gut from Day E 11 to Day E 16 of gestation. This period spans the time of enteric ganglion formation. Laminin and collagen type IV were studied by immunocytochemistry and proteoglycans by staining glycosaminoglycans with Alcian blue. Abnormalities of each of these components occur during development of the presumptive aganglionic bowel in the ls/ls mouse and could be detected as early as Day E 11. These defects consist mainly of an overabundance of these materials, both in defined basal laminae and throughout the extracellular space of the mesenchyme. Electron microscopic observations in the presumptive aganglionic ls/ls colon revealed a thickening of basal laminae and exceptionally wide intercellular spaces between smooth muscle myoblasts that contained an irregular fibrillar material, consisting of 4.5- to 6.0-nm filaments associated with 14- to 20-nm granules. Fibrillar and flocculant material was continuous with formed basal laminae, and was concentrated in the same areas found to have an overabundance of laminin immunoreactivity. These observations indicate that there is an accumulation of extracellular matrix material, including components of basal laminae, that (i) precedes the formation of enteric ganglia, (ii) is in the path through which enteric neural precursors from the crest would have to migrate, and (iii) is limited to the aganglionic and hypoganglionic ls/ls bowel. These data are consistent with the hypothesis that components of basal laminae contribute to the inability of crest cells to colonize the terminal bowel of ls/ls mice. PMID- 3338620 TI - Cell lineage conversion in the sea urchin embryo. AB - The mesoderm of the sea urchin embryo conventionally is divided into two populations of cells; the primary mesenchyme cells (PMCs), which produce the larval skeleton, and the secondary mesenchyme cells (SMCs), which differentiate into a variety of cell types but do not participate in skeletogenesis. In this study we examine the morphogenesis of embryos from which the PMCs have been removed microsurgically. We confirm the observation of Fukushi (1962) that embryos lacking PMCs form a complete skeleton, although in a delayed fashion. We demonstrate by microsurgical and cell marking experiments that the appearance of skeletogenic cells in such PMC-deficient embryos is due exclusively to the conversion of other cells to the PMC phenotype. Time-lapse video recordings of PMC-deficient embryos indicate that the converting cells are a subpopulation of late-ingressing SMCs. The conversion of these cells to the skeletogenic phenotype is accompanied by their de novo expression of cell surface determinants normally unique to PMCs, as shown by binding of wheat germ agglutinin and a PMC-specific monoclonal antibody. Cell transplantation and cell marking experiments have been carried out to determine the number of SMCs that convert when intermediate numbers of PMCs are present in the embryo. These experiments indicate that the number of converting SMCs is inversely proportional to the number of PMCs in the blastocoel. In addition, they show that PMCs and converted SMCs cooperate to produce a skeleton that is correct in both size and configuration. This regulatory system should shed light on the nature of cell-cell interactions that control cell differentiation and on the way in which evolutionary processes modify developmental programs. PMID- 3338621 TI - Organization and expression of three genes from the silkmoth early chorion locus. AB - Chorion genes in the silkmoth Bombyx mori are clustered in a small region of one chromosome. Genes are grouped within this locus according to their expression in either early, middle, or late stages of choriogenesis. The entire set of late genes and a large fraction of the middle genes have been cloned and extensively characterized. We report here the first molecular characterization of a set of early chorion genes clustered within a 22.5-kb region. Transcripts homologous to these genes appear in the very first choriogenic follicle but disappear with different kinetics. One of the three early genes, 5H4, is the first example of a chorion gene which is not a member of a multigene family, or divergently paired with another chorion gene. The other two early genes, (ErA.1 and ErB.1) are divergently paired with each other in the manner of the middle and late chorion genes. The common 5' region between ErA.1 and ErB.1 is significantly shorter and does not contain certain sequence elements shared by the highly conserved 5' regions of middle and late chorion gene pairs. This evidence taken together with the fact that 5H4 is unpaired indicates that the early genes may utilize a regulatory mechanism somewhat different from the middle and late gene families. PMID- 3338622 TI - Changes in the vascular extracellular matrix during embryonic vasculogenesis and angiogenesis. AB - We have previously characterized monoclonal antibodies against chick brain cells. One of them (14-2B2) brightly stained all capillaries in frozen sections of chick brain. Here we show that this antibody is directed against chick fibronectin. Using this antibody and polyclonal antibodies against laminin, we have studied the development of the vascular extracellular matrix. Vasculogenesis, the development of capillaries from in situ differentiating endothelial cells, was studied in yolk sac blood islands and intraembryonic dorsal aorta. Blood islands produced high levels of fibronectin but not laminin. Early intraembryonic capillaries all expressed fibronectin but little if any laminin. The dorsal aorta of a 6-day-old chick embryo has several layers of fibronectin-producing cells, but is devoid of laminin. Laminin expression commenced at Day 8 and by Day 10 an adult-like distribution was found in the aortic vascular wall. Angiogenesis, the formation of capillaries from preexisting vessels, was studied during brain development. Capillary sprouts invading the neuroectoderm at Embryonic Day 4 migrated in a fibronectin-rich matrix devoid of laminin. Ultrastructural immunolocalization demonstrated the presence of fibronectin exclusively on the abluminal site of the endothelial cells. Beginning on Day 6, laminin codistributed with fibronectin in brain capillaries. We conclude that immature capillaries migrate and proliferate in a fibronectin-rich extracellular matrix, which is subsequently remodeled acquiring basement membrane-like characteristics. We suggest that laminin expression is an early indication of vascular maturation. PMID- 3338623 TI - Cytoplasmic Ca2+ release induced by microinjection of Ca2+ and effects of microinjected divalent cations on Ca2+ sequestration and exocytosis of cortical alveoli in the medaka egg. AB - Intracellular release of Ca2+ by microinjection of Ca2+ was analyzed by measuring the luminescence of aequorin loaded in eggs of the medaka (Oryzias latipes). Microinjection of Ca2+ into the cortical cytoplasm induced propagative waves of cytoplasmic Ca2+ release and exocytosis of cortical alveoli initiated at the injection point. The Ca2+ wave was initiated with a time lag after some was sequestered at the region of the microinjection. Microinjection of Mg2+ or Mn2+ failed to trigger Ca2+ release and exocytosis. When the aequorin-loaded eggs were inseminated after microinjection of Mg2+, Mn2+, or Co2+ into a restricted region of the vegetal hemisphere, the wave of Ca release was propagated through the injected region toward the vegetal pole, but neither Ca sequestration (fall in Ca aequorin luminescence) nor exocytosis occurred at the area of cortex where the eggs were injected with these divalent cations. These results suggest that a significant period is required to induce Ca2+ release from cytoplasmic stores by the increased Ca2+ concentration and that both the phenomena of Ca2+ release and Ca sequestration are involved in the process of exocytosis. PMID- 3338624 TI - A possible maternal-effect mutant of Xenopus laevis I. Cytological and biochemical analyses of the unfertilized eggs and embryos. AB - In an effort to define the cause of the developmental arrest of offspring from a certain Xenopus female (designated as No. 65), we have examined eggs and embryos from the female both cytologically and biochemically. Light and electron microscopic observations revealed that all of the blastomeres from embryos of female No. 65 had multiple small spherical nuclei, while wild-type counterparts had a single lobulated nucleus. Two-dimensional gel electrophoretic analyses demonstrated that a major acidic protein, whose molecular weight was 38 kDa, was always found in samples from wild-type unfertilized eggs and embryos, but was not recognizable in those from female No. 65. These facts, coupled with the death of the offspring at gastrulation, suggest the possibility that female No. 65 carries a mutation of the ova-deficient type. PMID- 3338626 TI - Changes in the categorization of appetitive and aversive events during postnatal development of the rat. AB - Environmental stimuli are not clearly categorized into appetitive and aversive classes during the first postnatal week. Three- and 6-day-old rats are highly activated by nominally appetitive (milk infusions) and aversive (foot shock) stimuli. Both evoked the same generalized behavioral responses (rolling, curling). By 12 days of age, these stimuli were responded to differently; mouthing and probing occurred in response to milk while flinching and escape responses were observed to shock. The affective properties of mild shock were found to be hedonically opposite for 6- and 12-day-old pups. Six-day-olds showed an acquired preference for an odor paired with shock which increased with intensity (.1-.5 mA) similar to that observed with milk infusions. An acquired odor aversion was displayed by 12 days old using these shock parameters. These results suggest that young rat pups may not differentiate many appetitive and aversive events behaviorally or affectively until the second postnatal week. PMID- 3338625 TI - Experience during suckling alters later spatial learning. AB - These experiments explore the role of preweaning experience in learning during the juvenile period. Pups that had been reared with many nipples available reached criterion on an 8-arm radial maze in a few trials; conversely, pups reared with only a few nipples required 3 times the number of trials to reach criterion (Experiment 1). Pups that had been reared with relatively few nipples available rarely nipple-shifted, while those that had been reared with a particularly high density of nipples shifted more frequently (Expt 2). A rearing procedure was devised that allowed precise experimental control of all phases of the suckling experience (Expt 3). Allowing or preventing a single behavior, nipple-shifting, while holding all other variables constant, was sufficient to affect acquisition of the maze task. In Experiment 4, the specificity of the early experience for later tasks was explored using a variety of nonspatial, lever-pressing operants. Rearing condition did not affect acquisition of a lever pressing operant or of a visual discrimination task. However, pups reared with a high density of nipples responded at higher rates to a variable interval schedule and were more resistant to extinction. The possibility that strategy, rather than learning ability, was affected by rearing condition was assessed using a 2-arm maze task that was structured to present an optimal strategy of either win-shift or win-stay (Expt 5). The ease with which rats acquired the win-stay task was unaffected by rearing condition; all groups performed at about chance levels. However, pups reared with many nipples more readily acquired the win-shift task. PMID- 3338627 TI - Continuities in infant memory development. AB - Fifty-five 6- to 7-month-old human infants were trained in an operant conditioning procedure, adapted from a procedure developed for 3-month-olds, in which kicks were reinforced by conjugate movement of a mobile. Retention was assessed in a simple forgetting paradigm (Expt. 1) or in a reactivation paradigm (Expt. 2) with either the training mobile or a different one serving as the retrieval cue. In Experiment 1, retention was tested 1, 7, 14, or 21 days after training. When the training and test mobiles were the same, infants exhibited virtually no forgetting for 14 days, but forgetting was complete by 21. When the training and test mobiles were different, infants exhibited no retention, discriminating the novel mobile for as long as they could remember the contingency. In Experiment 2, when the training mobile was presented as a reminder, the forgetting previously seen after 21 days was alleviated; when a different mobile was the reminder, it was not. These findings reveal that the efficacy of a reminder is predicted by the efficacy of that same stimulus in cuing the original memory 24 hr following training. Although the 6-month-olds learned more rapidly and remembered longer than infants half their age, their memory processing was described by the same basic principles. PMID- 3338628 TI - Preweaning stimulation with urinary chemosignals and age of puberty in female mice. AB - Six experiments were conducted to assess the effects of preweaning stimulation with urinary chemosignals from four different sources on the age of sexual maturation in young female mice. The urinary chemosignals tested were those in male urine, urine from females in estrus, urine from pregnant or lactating females, and urine from females housed in groups. The split-litter technique was used for assigning mice to particular treatments. When treatments were applied during the period from 2 to 11 days postpartum, none of the chemosignals exerted any detectable influence on the age of first vaginal estrus. All 4 chemosignal treatments were effective in altering the age of puberty when treatment was applied daily from Days 12 to 21 postpartum. For urine from males and urine from estrous females, 3 days of treatment during the last 10 days prior to weaning at 21 days of age were sufficient to produce an acceleration of puberty. For urine from pregnant or lactating females, 5 days of treatment just prior to weaning were necessary to produce an acceleration of sexual development. For urine from grouped females, delays in puberty were produced only when the treatment lasted for 7 of the last 10 days prior to weaning. These findings suggest that the preweaning stimulus environment of young female mice may be important for their later sexual development. Further, use of the split-litter technique permitted the determination that variation in the age of puberty was smaller within than between litters; inheritance and/or maternal influences are clearly important factors affecting the age of sexual maturation. PMID- 3338629 TI - Terminology for use in investigations of nursing and suckling. PMID- 3338631 TI - Cholesterol absorption regulates cholesterol metabolism and plasma lipoprotein levels in patients with gut exclusions. AB - The occurrence of cholesterol malabsorption and its role in the regulation of cholesterol metabolism were studied in 30 patients with an earlier gut resection and 9 patients with a jejunoileal bypass for treatment of obesity. Fractional cholesterol absorption varied from 0.1% to 70%, and was lowest in jejunoileal bypass (8.3%) associated with severe fat and moderate bile acid malabsorptions and in 15 patients with a long small-intestinal resection (20.4%) associated with severe bile acid and moderate fat malabsorption. Seven resected patients with normal fecal fat and bile acids and 8 resected patients with malabsorption of only bile acid had normal cholesterol absorption. Low fractional cholesterol absorption was associated with a short length of the remaining proximal small intestine, high dietary intake of plant sterol, and high fecal fat and neutral sterol excretions, but not with bile acid malabsorption. In the whole study population, plasma levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol were positively correlated with fractional cholesterol absorption and the amount of total, dietary, and biliary absorbed cholesterol and were negatively correlated with fecal cholesterol elimination as neutral sterols (less so as bile acids) and cholesterol synthesis. The results emphasize that, in patients with ileal exclusion, plasma levels of low-density lipoprotein and high density lipoprotein cholesterol are regulated more effectively by cholesterol than by bile acid malabsorption. Moreover, although the fecal loss of bile acids is the main determinant in cholesterol elimination and stimulation of cholesterol synthesis in patients with intestinal exclusions, intestinal cholesterol absorption also contributes noticeably to the regulation of cholesterol synthesis. PMID- 3338630 TI - Selective recognition of mucosal lymphoid high endothelium by gut intraepithelial leukocytes. AB - Circulating precursors of mucosal immunoglobulin A plasma cells and T-cell immunoblasts migrate selectively into mucosal sites from the blood, but the mechanisms controlling this selective trafficking have not been determined. One possibility is that the site-specific extravasation of circulating effector cell populations is determined by organ-specific endothelial cell recognition mechanisms. Here we have assessed the ability of isolated mouse gut intraepithelial lymphocytes to recognize and bind to mucosal versus nonmucosal lymphoid organ high endothelial venules, vessels that support high levels of lymphocyte traffic in vivo. In an in vitro assay of lymphocyte interaction with high endothelial venules in frozen sections, intraepithelial leukocytes bind well to high endothelial venules in Peyer's patches but, unlike most circulating B and T lymphocytes, are unable to interact with peripheral lymph node high endothelial venules. Furthermore, we show by in situ immunohistology and in cell suspension immunofluorescence studies that intraepithelial leukocytes fail to stain with a monoclonal antibody, MEL-14, against putative lymphocyte receptors for lymph node high endothelial venules. Thus, they lack a cell surface glycoprotein required for homing to peripheral nodes. The demonstration of organ-specific recognition of endothelial cells by a normal mucosal effector lymphocyte population suggests that selective interactions with endothelium may play an important role in controlling the distribution of effector cells in vivo. The utilization of organ specific endothelial cell recognition mechanisms by circulating precursors of mucosal effector cells could explain both the unification of immune responses in diverse mucosal sites and the physiologic segregation of mucosal from nonmucosal immune mechanisms. PMID- 3338632 TI - Role of the duodenum in the control of canine gastrointestinal motility. AB - This study was designed to determine the role of the duodenum in controlling the interdigestive migrating motor complex of the canine stomach and small intestine. The motility patterns of 4 dogs were studied before and after resection of the entire duodenum with reimplantation of bile and pancreatic ducts. Before duodenectomy, plasma concentrations of motilin and pancreatic polypeptide varied cyclically with the migrating motor complex. After duodenectomy, the migrating motor complex was abolished in the stomach in 3 of the 4 dogs during fasting. The other dog demonstrated what appeared to be an intermittent cyclic increase in gastric contractile activity, but with markedly abnormal characteristics and at irregular intervals. The jejunal migrating motor complex continued to cycle after duodenectomy in all 4 dogs, but the mean period was shorter than before duodenectomy (83 min vs. 147 min, p less than 0.01). Duodenectomy abolished the cyclic variations of plasma motilin and pancreatic polypeptide and lowered the concentration of both peptides during all phases. This study suggests that the duodenum plays an important role in the initiation of the gastric migrating motor complex and in the coordination of interdigestive gastrointestinal motor activity, possibly by the release of motilin. PMID- 3338633 TI - Different binding properties of muscarinic M2-receptor subtypes for agonists and antagonists in porcine gastric smooth muscle and mucosa. AB - The hypothesis that muscarinic receptors on smooth muscle differ from those in epithelial glands was tested by comparing the properties of muscarinic binding sites in porcine fundic smooth muscle with those in mucosal membranes. The binding of agonists and of antagonists was assessed by displacement of [3H]N methylscopolamine. Pirenzepine (M1-antagonist) labeled low-affinity binding sites in smooth muscle (KD = 229 nM) and in mucosa (KD = 124 nM) consistent with the presence of M2 sites. Carbachol interacted with a high-affinity (KD = 164 nM) and a low-affinity (KD = 18.2 microM) state of binding sites in smooth muscle. Guanyl 5'-yl-imidodiphosphate converted all sites to the low-affinity state. N ethylmaleimide pretreatment increased the affinity of carbachol and the proportion of high-affinity sites. In clear contrast, only low-affinity sites of carbachol were detectable in mucosa (KD = 17 microM) that were not modulated by N ethylmaleimide or guanyl 5'-yl-imidodiphosphate. The cardioselective antagonist AF-DX 116 displayed low affinity to mucosal binding sites (KD = 3.4 microM), whereas its affinity to smooth muscle was 503 nM. The antagonist hexahydro-sila difenidol had a very high affinity (KD = 2.9 nM) to mucosal receptors, whereas its affinity to smooth muscle sites was 88 nM. These data show that muscarinic M2 binding sites in mucosa and smooth muscle can be distinguished by both agonist and antagonist binding experiments, and suggest the existence of different subtypes of M2-binding sites in these tissues. PMID- 3338634 TI - Effect of acute Yersinia enterocolitica infection on in vivo and in vitro small intestinal solute and fluid absorption in the rabbit. AB - The impact of acute Yersinia enterocolitica infection on jejunal and ileal solute and water transport was examined. New Zealand White rabbits (500-600 g) were infected with Y. enterocolitica and compared with unmanipulated controls and pair fed controls. Transport studies were performed 6 days after infection on jejunum and ileum by an in vivo single-pass perfusion technique and in vitro under short circuited conditions in Ussing chambers. When studied in vivo, Y. enterocolitica infection resulted in decreased water and electrolyte absorption in the jejunum under basal conditions and in both jejunum and ileum in the presence of glucose. Glucose absorption was also decreased in jejunum and ileum. When studied in vitro, net basal Na+ and Cl- transport was not altered in jejunal or ileal epithelium from infected animals. Glucose-stimulated Na+ absorption was decreased in ileal epithelium, and absorption of 3-O-methyl-D-glucose was decreased in both jejunum and ileum. Secretory capacity of Cl-, as assessed by isobutylmethyl xanthine stimulation, was unimpaired in both jejunum and ileum. Decreased food intake alone, in the pair-fed animals, had little effect on intestinal transport. The results indicate that malabsorption, rather than active intestinal secretion, is the major small intestinal transport defect in acute Y. enterocolitica infection. Furthermore, the abnormalities can be directly attributed to injury induced by the organism itself, rather than malnutrition. PMID- 3338635 TI - Intestinal microvascular exchange in the rat during luminal perfusion with formyl methionyl-leucyl-phenylalanine. AB - Formyl-methionyl-leucyl-phenylalanine (FMLP), a peptide released from bacteria in the gut lumen, is known to both attract and activate neutrophils. The aim of this study was to determine whether luminal perfusion with 1 microM FMLP alters microvascular permeability, blood flow, and neutrophil migration in the small intestine of control rats and rats treated with antineutrophil serum. Microvascular permeability to total plasma proteins was determined from an analysis of lymphatic protein fluxes. Myeloperoxidase activity was used as an index of tissue neutrophil count. Intestinal blood flow was measured using radiolabeled microspheres and the reference blood sample method. In control rats, luminal perfusion with FMLP caused significant increases in blood flow, lymph flow, lymph protein clearance, and microvascular permeability, but it did not alter tissue myeloperoxidase activity. In rats treated with antineutrophil serum, tissue myeloperoxidase levels were reduced by approximately 55%, and the FMLP induced changes in lymph flow, lymph protein clearance, and microvascular permeability were significantly attenuated. In vitro experiments with isolated rat neutrophils revealed that 1 microM FMLP elicits significant chemotaxis and degranulation yet minimally enhances superoxide production. The results of this study indicate that peptides produced by microorganisms in the gut lumen can increase intestinal microvascular permeability. The FMLP-induced alterations in microvascular exchange appear to be mediated by activated neutrophils. PMID- 3338636 TI - Essential fatty acid deficiency and postresection mucosal adaptation in the rat. AB - The effect of short-term (biochemical) and long-term (clinical) essential fatty acid (EFA) deficiency on mucosal adaptation was studied in a surgical model of short bowel syndrome. Rats fed an EFA-deficient diet for 4 wk had biochemical evidence of EFA deficiency (hepatic and red blood cell triene to tetraene ratios greater than 0.4). Resected animals (70% proximal jejunoileal resection) receiving an EFA-deficient diet had a significantly impaired intestinal mucosal hyperplasia response in all remaining small bowel segments compared with resected controls. The effect of refeeding a control diet to clinically EFA-deficient resected rats was also evaluated. Short-term refeeding (2 wk) of a control diet resulted in a significant return toward normal tissue triene to tetraene ratios. Concomitantly, refed animals had significantly greater mucosal adaptation in the remaining duodenal/jejunal segment compared with resected animals maintained on an EFA-deficient diet postoperatively. These experiments underscore the dynamic nature of tissue EFA status and the importance of fatty acids in the normal compensatory mechanisms of mucosal adaptation after resection. PMID- 3338637 TI - Trends in peptic ulcer surgery. A population-based study in Rochester, Minnesota, 1956-1985. AB - We evaluated trends in peptic ulcer surgery among residents of Rochester, Minnesota, where medical care delivered to the population by all providers is well documented. The incidence of elective operations on previously unoperated patients declined dramatically during the 30-yr study period, from 49/100,000 population per year in 1956-1960 to 6/100,000 per year in 1981-1985. The decline was greatest for men with duodenal ulcer, less for men and women with gastric ulcer, and least for women with duodenal ulcer. These trends were established long before the introduction of H2-receptor drug therapy in 1977. In contrast to elective operations, the incidence of emergent operations remained at about 10/100,000 population per year. Perhaps because of an increasing proportion of emergency operations, overall survival appeared to worsen from the first decade of study to the last; but, after adjustment for age at operation and sex, no difference in survival over time was detected. PMID- 3338638 TI - Subepithelial tissue pH of rat gastric mucosa exposed to luminal acid, barrier breaking agents, and hemorrhagic shock. AB - Tissue pH in the immediate subepithelial layer of rat gastric mucosa was measured using H+-selective microelectrodes. Exposure of the mucosa to luminal acid (50 150 mM) caused a significant acidification of the subepithelial tissue. Contrary to expectation, disruption of the mucosal barrier with taurocholate (10 mM), acetylsalicylic acid (10 mM), or ethanol (20% vol/vol) during acid (100 mM HCl) perfusion promoted no further acidification of the subepithelial tissue but rather caused an alkalinization of the primarily acidified subepithelial tissue. When hemorrhagic shock was induced during acid perfusion, a profound acidification of the subepithelial tissue occurred even though a much lower luminal acidity (10 mM HCl) was used. Also, taurocholate had no alkalinizing influence on subepithelial pH during hemorrhagic shock, but caused a rapidly progressing and irreversible drop of the subepithelial tissue pH. The findings suggest that in normal stomach with intact "mucosal barrier," H+ back-diffusion occurs during exposure to acid. However, disruption of the mucosal barrier seems to lead to alkali (HCO3-) efflux from the mucosa, which neutralizes the influxing H+, thus "masking" H+ back-diffusion and protecting the mucosa. Yet, when adequate supply of HCO3- to the mucosa is blocked during exposure to a barrier breaking agent and acid, increased H+ back-diffusion becomes again "unmasked," leading to extensive acidification and ulceration of the mucosa. PMID- 3338639 TI - Local depot methylprednisolone injection for painful anal Crohn's disease. AB - Treatment, by local depot methylprednisolone injection, of severe anal pain in Crohn's disease not associated with overt sepsis is reported. It has given dramatic relief in 5 patients, but has not been successful in 2 patients where anal disease was in continuity with severe rectal involvement. Treatment has been effective for greater than 1 yr, and no complication of the technique has been found on regular follow-up. When compared with previous attempts at treatment, the beneficial results attained with methylprednisolone injection suggest that the effect is more than a placebo response. Careful patient selection to exclude overt sepsis or severe rectal disease is recommended before proceeding to steroid injection. PMID- 3338640 TI - Effects of changes in infusion rate versus glucose concentration on absorption in infant miniature pig small intestine. AB - The effect of changes in the rate of infusion versus glucose concentration on glucose, water, and sodium absorption was studied in 20 infant miniature pigs using the single-pass small intestinal perfusion technique. During infusions of glucose loads of up to 75.0 mumol/min, glucose absorption increased similarly whether rate of infusion or glucose concentration was increased. Beyond 75.0 mumol/min, glucose absorption was not altered by changes in infusion rate, but was enhanced by increases in glucose concentration (slope of rate vs. concentration, p less than 0.0001). Net water and sodium absorption were similar in the two groups except for a decrease at the highest glucose concentration (rate vs. concentration at 187.5 mumol/min, p less than 0.05). A glucose concentration of 112.5 mM resulted in maximal glucose, water, and sodium absorption. PMID- 3338641 TI - 16,16-Dimethyl prostaglandin E2 alleviates jejunal microvascular effects of ethanol but not the ethanol-induced inhibition of water, sodium, and glucose absorption. AB - To examine the relation between ethanol-induced microvascular and absorptive changes, we have investigated the effect of 16,16-dimethyl prostaglandin E2 on the jejunal intraluminal plasma albumin loss (which was taken as a measure of microvascular changes) and the inhibition of water, sodium, and glucose transport caused by intraluminal ethanol. A group of 8 dogs received intravenously 16,16 dimethyl prostaglandin E2 at a dose of 0.1 microgram/kg as a bolus followed by 0.05 microgram/kg.hour for 2 h (prostaglandin-treated group). A second group of 8 dogs received no 16,16-dimethyl prostaglandin E2 (untreated group). In each dog of both groups, one jejunal segment was perfused with an ethanol-free solution (control segment) and an adjacent segment was perfused with the same solution containing 6% (wt/vol) ethanol (ethanol-perfused segment). The albumin loss (mg/g dry gut wt.90 min, mean +/- SE) by the control and the ethanol-perfused segments was 0.76 +/- 0.23 and 8.29 +/- 1.27, respectively, in the untreated group, and 0.66 +/- 0.23 and 4.81 +/- 0.67, respectively, in the prostaglandin-treated group. The ethanol-induced increase in albumin loss was significant in both groups, but was significantly lower (p less than 0.05) in the prostaglandin treated group than in the untreated group. Intraluminal ethanol depressed net water, sodium, and glucose transport by 74%, 52%, and 22%, respectively, in the untreated group, and by 92%, 65%, and 38%, respectively, in the prostaglandin treated group. The magnitude of this depression did not differ significantly between the two groups. As 16,16-dimethyl prostaglandin E2 attenuated the ethanol induced plasma albumin loss, but not the inhibition of water, sodium, or glucose transport, we conclude that the microvascular and the absorptive changes produced by ethanol are not mediated by the same mechanism. PMID- 3338642 TI - Serum glucose concentration as a modulator of interdigestive gastric motility. AB - The objective of this study was to examine the effect of serum glucose concentration on interdigestive gastrointestinal motility and plasma motilin levels in humans. Motility studies were performed for a 3-h baseline period and a 3-h test period during which serum glucose levels were maintained with a glucose clamp at 250, 175, 140, or 120 mg/dl. During the basal recording, three phases of the interdigestive migrating motor complex (MMC) were easily recognizable, with a mean cycle duration of 97 +/- 12 min. Plasma motilin levels fluctuated in phase with the MMC. Gastric contractions were nearly absent at a serum glucose level of 250 mg/dl and markedly reduced at 175 and 140 mg/dl. Gastric phase III activity was inhibited during these infusions. Gastric contractions and phase III activity were not affected by glucose infusion at 120 mg/dl. In contrast, the frequency of duodenal phase III activity was unchanged at all levels of glucose infusion. Mean motilin levels were significantly reduced during glucose infusion at 250 and 175 mg/dl (p less than 0.05), but not at 140 and 120 mg/dl. We conclude that hyperglycemia inhibits the occurrence of the MMC in the stomach and suppresses plasma motilin levels. The differential sensitivity of motility and motilin concentration to different degrees of hyperglycemia suggests that hyperglycemia can inhibit antral motility independent of plasma motilin. In contrast, the duodenal MMC appears to be insensitive to hyperglycemia. This suggests that the antral and duodenal MMCs are mediated by different mechanisms. Our observations indicate the importance of serum glucose in regulating gastric motility. PMID- 3338643 TI - Pancreatic polypeptide secretion from the isolated perfused ventral and dorsal areas of the rat pancreas. AB - The secretion of pancreatic polypeptide (PP) by neuropeptides [vasoactive intestinal polypeptide, gastrin-releasing peptide (GRP), neuromedin B, and neuromedin C] and carbachol was investigated using the isolated perfused ventral part of the rat pancreas, with or without atropine, and a specific radioimmunoassay for rat PP. The release of PP from the dorsal part of the rat pancreas by GRP and carbachol was also studied. Carbachol and GRP stimulated, in a dose-dependent manner ranging from 10(-6) to 10(-9) M, PP secretion from the ventral part of the pancreas. Maximum responses were observed with 10(-7) to 10( 8) M carbachol and 10(-7) M GRP. The response with 10(-7) M carbachol was biphasic and was abolished by 10(-5) M atropine. The response with 10(-7) M GRP, however, was transient, monophasic, and not inhibited by atropine. Vasoactive intestinal polypeptide (10(-7) M) stimulated a weak PP secretion that was not inhibited by atropine. The potency of GRP and vasoactive intestinal polypeptide relative to carbachol at 10(-7) M was 24% and 7%, respectively. Neuromedin C had almost the same bioactivity as GRP with respect to the release of PP, whereas neuromedin B was one-third less potent than GRP and neuromedin C. The relative secretion of PP from the dorsal compared with the ventral part of the pancreas after stimulation by 10(-7) M carbachol and GRP was 19% and 22%, respectively. These data show that peptidergic nerves may play some role in PP secretion. In addition, the main source of PP to the systemic circulation may be the ventral part of the pancreas. PMID- 3338644 TI - Lactulose detoxifies in vitro short-chain fatty acid production in colonic contents induced by blood: implications for hepatic coma. AB - Short-chain (C2-C6) fatty acids constitute the major anions of colonic contents. Acetate is nontoxic in contrast to C(3)4-C6 fatty acids, which induce coma in animals and have been reported to be of importance in the development of hepatic coma in humans. An in vitro fecal incubation system was used to demonstrate how blood, hemoglobin, albumin, lactulose, galactose, fructose, and glucose influence short-chain fatty acid production in the colon. Blood, hemoglobin, and albumin caused increased production of all C2-C6 fatty acids, with the most pronounced increase (fourfold) in C4-C6 fatty acids. Lactulose was converted to acetate only, as were its monosaccharide components, D-galactose and D-fructose. In assays incubated with blood, the production of C4-C6 fatty acids was completely inhibited by lactulose, D-galactose, D-fructose, and D-glucose, respectively, whereas the production of acetate was increased. Lactulose thus "detoxified" the profile of short-chain fatty acids produced in the presence of blood and proteins, indicating that colonic fermentative bacteria prefer lactulose to blood when both substrates are available. The effect of lactulose in the treatment of hepatic coma caused by episodes of gastrointestinal bleeding may therefore be due to a shift in bacterial metabolism from blood or proteins, or both, to lactulose in the colon, resulting in a simultaneous reduction in toxic nitrogenous and organic acid products. PMID- 3338645 TI - Gastroduodenal regulation of common duct bile flow in the dog. AB - We investigated the relationship between the entry of individual drops of bile into the duodenum and gastroduodenal motor activity in the fasted state in 10 conscious dogs. The common bile duct was transected and a catheter was inserted through each end. The exteriorized catheters were connected to a photometric drop flow meter. During phase III activity, bile entered the duodenum in single drops, only in between two consecutive contractions, or as a series of drops during transient inhibition of duodenal contractions by antral phase III contractions. During phase II activity bile also entered the duodenum, usually in between contractions or when the duodenum was intermittently quiescent. Bile entered the duodenum during a duodenal contraction only when the contraction amplitude was less than 15% +/- 1% (mean +/- SE) of the maximal amplitude during phase III contractions. Bile flow into the duodenum showed a cyclic pattern with a peak during late duodenal phase II activity and a trough during duodenal phase I activity only when phase III activity originated in the duodenum and migrated caudad. There was no cyclic pattern of bile flow when phase III activity originated in the proximal jejunum and migrated caudad. The total volume of bile flow in a migrating motor complex cycle and bile flow rate were greater when phase III activity started in the proximal jejunum than when it started in the duodenum. We conclude that gastroduodenal contractions play an important role in the regulation of bile flow into the duodenum. The cyclic pattern of bile flow is altered when phase III activity starts ectopically in the jejunum. PMID- 3338646 TI - Receptor-mediated binding and uptake of immunoglobulin A by human liver. AB - We have studied the molecular mechanisms of the binding and uptake of secretory and serum immunoglobulin A (IgA) of both subclasses (1 and 2) and molecular forms (monomer and polymer) by the particulate fraction of human liver homogenate and by a human hepatoma cell line (HepG2). Inhibition by asialoorosomucoid and the requirement for the presence of calcium indicated that the binding of secretory IgA and polymeric IgA1 was mediated by the asialoglycoprotein receptor. Secretory component, which functions as a receptor for polymeric IgA in several animal species, was detected in the epithelial cells of bile ducts, but not in hepatocytes. Secretory IgA and all molecular forms and subclasses of serum IgA were bound by HepG2 cells, which do not express secretory component. The requirement for the presence of calcium, the presence of a terminal galactose residue in IgA, and the molecular weight of the major plasma membrane protein responsible for binding (41,700 daltons) indicated the involvement of asialoglycoprotein receptor. Immunoglobulin A proteins bound by HepG2 cells were endocytosed and catabolized. PMID- 3338647 TI - Hepatic handling of a synthetic gamma-labeled bile acid (75SeHCAT). AB - 75Se-homocholic acid-taurine (75SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for 75SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, [14C]cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for 75SeHCAT, but significantly lower for 99mTc hepatoiminodiacetic acid (6% vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for 75SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for 75SeHCAT (14.3% and 1.5% dose/min) than for [14C]cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (275 vs. 670 ml/min). In vitro, 75SeHCAT was bound to serum proteins more completely than [14C]cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that 75SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as [14C]cholic acid-taurine, probably due to its stronger protein binding. The clinical value of 75SeHCAT in assessing liver disease should be investigated. PMID- 3338648 TI - Effects of ethanol, acetaldehyde, and lactate on proteoglycan synthesis and proliferation of cultured rat liver fat-storing cells. AB - The hypothesis that ethanol and some of its metabolites are directly involved in the process of fat-storing cell activation and stimulated proteoglycan synthesis in alcoholic liver injury was investigated. The effects of short-term (24 h) and long-term (4 days) exposure of rat liver fat-storing cells at various times of culture to ethanol, acetaldehyde, and lactate on the synthesis of proteoglycans and total protein and on the proliferation activity of the cells were studied. Ethanol and lactate did not stimulate the incorporation of [35S]sulfate into glycosaminoglycans. Acetaldehyde inhibited strongly glycosaminoglycan synthesis, reaching 50% inhibition at 330 mumol/L. The compound preferentially inhibited the synthesis of dermatan sulfate. No significant changes of glycosaminoglycan chain length or of the degree of polysaccharide sulfation were noted in acetaldehyde treated cultures. The inhibition was reversed by the addition of beta-D xylopyranoside (0.5 mmol/L), an artificial initiator of chain elongation, to the medium. Total protein synthesis, cell number, deoxyribonucleic acid content of the cultures, and [3H]thymidine incorporation were not affected by the compounds. The results do not support the view that ethanol, its oxidation product acetaldehyde, or lactate are directly involved in the activation of fat-storing cells and in enhanced matrix proteoglycan synthesis and secretion. PMID- 3338649 TI - Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome. AB - A 29-yr-old woman presenting with granulomatous colitis and a chronic perirectal abscess was found to have localized cryptococcosis associated with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome. Similarity to previous cases of esophageal cryptococcosis and ileocecal histoplasmosis suggests an association between the hyperimmunoglobulinemia E-recurrent infection syndrome and localized fungal infections of the alimentary tract. To our knowledge, this is the first well-documented case of cryptococcosis confined to the colon and perirectal tissues. PMID- 3338651 TI - Intestinal lymphangiectasia and the yellow nail syndrome. PMID- 3338650 TI - Ornithine decarboxylase activity in Barrett's esophagus: a potential marker for dysplasia. AB - Ornithine decarboxylase activity is known to be increased in certain premalignant conditions. We determined the activity of this enzyme in mucosal biopsy specimens from 15 patients with Barrett's esophagus. Ornithine decarboxylase was greater in Barrett's mucosa than in squamous esophageal or gastric mucosa. In Barrett's mucosa from 4 patients with dysplasia, the enzyme activity was greater than in 11 patients without dysplasia (1.6 +/- 0.35 vs. 0.19 +/- 0.08 U/mg protein; p less than 0.005). Increased ornithine decarboxylase activity in biopsy specimens of Barrett's mucosa may represent a marker for dysplasia. PMID- 3338653 TI - The Golden State vs. "the golden years:" getting physicians ready for change. PMID- 3338652 TI - Diabetes-related impotence: putting new knowledge to waste. PMID- 3338654 TI - Geriatric knee disorders, Part I: Evaluative techniques. AB - It is important to remember that knee disorders seen in the elderly are distinctly different from those seen in the younger individual. In the elderly, the problems are generally the result of chronic processes and, occasionally, an acute process on top of a chronic disorder. A careful history and physical examination should enable the physician in most cases to make the correct diagnosis. However, at times, specific laboratory studies may be ordered to confirm the diagnosis. In part I of this two-part review of geriatric knee disorders, the authors will focus on the anatomy, history, and physical examination of the knee joint. Common knee disorders specific to the elderly will be discussed in part II. PMID- 3338655 TI - Bladder and rectal complications following radiotherapy for cervix cancer. AB - One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad. PMID- 3338656 TI - Melanosis of the cervix. AB - Benign and malignant melanotic cervical lesions are rare and require biopsy to rule out melanoma. Reported is a case of cervical melanosis, defined as benign epithelial pigmentation. PMID- 3338657 TI - Neuroendocrine (Merkel cell) carcinoma of the vulva. AB - The clinical, histopathologic, and ultrastructural features of a primary cutaneous vulvar neuroendocrine neoplasm (Merkel cell carcinoma) are presented. This recently described tumor arises in the dermis and is often aggressive with metastasis to regional lymph nodes. Ultrastructural study of this case reveals morphologic similarities to normal cutaneous Merkel cells, including peripherally located dense-core neurosecondary-like granules, and immunohistochemical studies revealed ACTH within neoplastic cells. By light microscopy this tumor is readily confused with other primary or metastatic cutaneous neoplasms; therefore, the importance of electron microscopic examination is emphasized for definitive diagnosis of this unusual tumor. PMID- 3338658 TI - Basal cell carcinoma of the vulva with inguinal lymph node metastases. AB - Basal cell carcinoma of the vulva is a rare neoplasm which is generally thought to be indolent, locally invasive, and nonmetastasizing. A case of basal cell carcinoma of the vulva with metastases to the ipsilateral inguinal lymph nodes is presented. This is the third well-documented case in the literature of vulvar basal cell carcinoma with inguinal lymph node metastases. PMID- 3338659 TI - Comparative morphometric study on the depth of invasion in vulvar carcinoma. AB - Various studies assess the significance of depth of invasion as an important prognostic factor in squamous cell carcinoma of the vulva. However, methodologic problems exist with regard to the measurement points. While the deepest point of invasion can be measured accurately, the upper reference point is arbitrarily chosen. The goal of the present study was to identify the method of measurement and the threshold value, allowing the clearest prognostic differentiation between groups of patients with vulvar carcinoma. The study involved 124 patients treated between 1971 and 1980, who had received identical treatment (simple vulvectomy followed by local and inguinal irradiation) and identical histopathologic workup (large-scale sections). Beginning with the deepest point of tumor invasion, comparative measurement was carried out with three different points of reference: to the basement of the most superficial dermal papilla (method A), to the surface of the tumor (method B), and to the basement membrane of the deepest rete ridge (method C). The data were used to determine differences in specified end points. The results and conclusions are as follows: (1) The morphometrically determined degree of tumor invasion had prognostic significance. (2) Measurement of tumor thickness (method B) prognostically differentiates patient groups better than measurement of invasion from the most superficially lying epithelial papilla (method A), if classified into tumors up to and over 0.5 cm. (3) Patients with superficial invasive vulvar carcinomas up to 0.5 cm can be further prognostically differentiated into two groups, when measuring depth of invasion from the deepest rete ridge (method C), and classifying into tumors up to and over 0.3 cm. PMID- 3338660 TI - Pelvic irradiation for stage II ovarian carcinoma. AB - Over a 20-year period, 34 patients with FIGO stage II ovarian carcinoma were treated with postoperative pelvic irradiation at the University of Michigan. Complications of radiation treatment were minimal. The overall actuarial disease free 5-year survival was 53%. This was not significantly different for substages IIA, IIB, or IIC. Patients with well-differentiated tumors had a significantly better survival than patients with moderate or poorly differentiated tumors (P less than 0.05). The implications for managing stage II ovarian carcinoma are discussed. PMID- 3338661 TI - Treatment of recurrent and metastatic cervical cancer with cis-platin, doxorubicin, and cyclophosphamide. AB - The combination of cisplatin, doxorubicin, and cyclophosphamide was used to treat 28 patients with recurrent and metastatic cervical cancer. Five patients had a complete response and one patient had a partial response, yielding a total response rate of 21%. Eleven patients had stable disease. The median survival for the whole group was 42 weeks. Responders had a statistically significant prolongation of survival at a median of 113 weeks (P less than 0.01). There was no statistically significant difference in progression-free interval between responders and patients with stable disease. The overall median progression-free survival was 26 weeks. The toxicities noted were primarily nausea, vomiting, and myelosuppression. The combination of cis-platin, doxorubicin, and cyclophosphamide has modest effectiveness in the treatment of metastatic or recurrent carcinoma of the cervix. PMID- 3338662 TI - A comparison of findings at second-look laparotomy with preoperative computed tomography in patients with ovarian cancer. AB - Prior to undergoing second-look laparotomy, 57 patients with ovarian cancer were evaluated with computed axial tomography (CT). All patients were clinically free of disease following chemotherapy. At laparotomy, 25 patients had visible evidence of disease, 9 had microscopic disease only, and 23 were free of cancer. Tumor was correctly identified on CT in 9 of the 25 patients (36%) with macroscopic disease. Tumors smaller than 2 cm in size were not detected by CT. CT suggested disease in 8 of the 32 patients (25%) who were free of macroscopic disease. CT provides useful information when it is abnormal. Fine needle aspiration of suspicious areas can spare some patients laparotomy. However, CT has a significant false-negative rate due to its inability to detect small volume disease. Patients with negative CT will continue to require reexploration and tissue confirmation to assess the need for further therapy. PMID- 3338664 TI - Recurrent acute leg cellulitis in patients after radical vulvectomy. AB - Recurrent acute leg cellulitis (ALC) known to occur in patients with impaired venous or lymphatic circulation was studied in 126 patients after radical vulvectomy with lymphadenectomy through the years 1973 to 1985. Among these patients surveyed for a total period of 6153 patient months, 33 (26%) experienced 75 episodes of ALC. Recurrent attacks were frequently observed. Although antimicrobial treatment was often started, clinical signs resolved also in 9 patients without antimicrobial treatment. To prevent recurrencies penicillin prophylaxis was given to 23 patients. Only 1 of them had once a mild attack of ALC, whereas recurrent attacks occurred frequently in those patients not receiving penicillin prophylaxis. Although penicillin prophylaxis was successful in preventing the recurrence of ALC the risk-benefit ratio of this approach has not been ascertained. The etiology and pathogenesis of recurrent ALC is discussed. Analysis of a number of assumed risk factors for ALC showed that the frequency of ALC was significantly higher in patients colonized with beta hemolytic streptococci, mainly group B, than in patients not colonized with these microorganisms just prior to surgery. This suggests that non-group A beta hemolytic streptococci are involved in the onset of ALC in patients after radical vulvectomy. However, portals of entry for microorganisms were not apparent in any of our patients. PMID- 3338663 TI - Complications of Tenckhoff catheter implantation in patients with multiple previous intraabdominal procedures for ovarian carcinoma. AB - In patients with minimal residual ovarian carcinoma after aggressive surgical and chemotherapeutic treatment, nephrotoxicity and/or peripheral neuropathy often prohibit continued treatment with intravenous combination cisplatin-based chemotherapy. It is attractive to continue treatment of these patients with intraperitoneal (ip) delivered chemotherapy. From 1981 through 1984 a Tenckhoff catheter was implanted in 59 women for ip chemotherapy after a staging laparoscopy or laparotomy. Minor complications occurred in 8 patients and could be treated conservatively. Ten patients suffered major complications, leading to three (re)laparotomies and catheter extraction in 7 of 10 patients. No patient died of complications, but mean hospitalization time of patients with major complications was 25 days as compared to 11 days for patients without complications. An analysis of nine factors that could lead to postoperative complications failed to reveal a statistically significant risk factor. From this study no profile of a typical high-risk patient emerges. PMID- 3338665 TI - Clinical relevance of various microscopical features of the second-look specimen in advanced ovarian cancer. AB - The second-look specimens of 70 patients with advanced ovarian cancer (FIGO 2B, 3, and 4) were reviewed and classified according to four categories: no response to chemotherapy (category a), predominantly histologically viable tumor with some necrotic and/or fibrotic tissue (category b), predominance of fibrosis and recrosis (category c), and no evidence of tumor, i.e., pathologically proven complete response (PCR) (category d). All of the patients in categories a and b had died because of ovarian cancer at the end of the observation period. In category c, 17/25 patients eventually achieved a PCR as established at a third look procedure. The median survival of 56 months in this group was lower than that of the patients in category d (64 months), although this difference was without statistical significance. These observations underscore the importance of the microscopical features of the second-look specimen for the treatment of advanced ovarian cancer. PMID- 3338667 TI - Occurrence of epidermal growth factor receptors in human adnexal tumors and their prognostic value in advanced ovarian carcinomas. AB - Ninety-eight different malignant adnexal tumors were analyzed for the presence of epidermal growth factor (EGF)-specific binding sites and binding parameters were calculated by Scatchard plot analysis [G. Scatchard, Ann. N.Y. Acad. Sci. 51, 660 672 (1949)]. Thirty-four biopsies were EGF receptor (EGF-R) positive with dissociation constants (KD) of 0.5-12 X 10(-9) M and binding capacities (Bmax) of 2-250 fmol/mg. One tumor had a KD of 60 X 10(-9) M and a Bmax of 1660 fmol/mg. The correlation of EGF-R status with clinical parameters showed no significant differences in primary, metastatic, or recurrent tumors, histological subtype, tumor differentiation, and tumor residual after primary surgery. As an inverse correlation, EGF-R-positive tumors are 39% and EGF-R-negative tumors 60% progesterone receptor positive. A response to chemotherapy was noticed in 50% of EGF-R-positive ovarian carcinomas with a mean survival time of patients of 28 months. The response rate of EGF-R negative ovarian carcinomas was 12% with a mean survival time of 16 months. Regarding the treatment schedule the major differences were noticed in the cis-platinum plus cyclophosphamide treatment group. These results suggest that the biology of ovarian carcinomas is influenced by growth factors and their receptors, which can be used as prognostic factors. PMID- 3338666 TI - Evaluation of bolus cis-platinum and continuous 5-fluorouracil infusion for metastatic and recurrent squamous cell carcinoma of the cervix. AB - The combination of cis-platinum and 5-fluorouracil has been reported to act synergistically with improved response rates in squamous cell carcinomas of the head and neck. The activity of bolus cis-platinum and continuous infusion of 5 fluorouracil in 24 patients with recurrent and metastatic squamous cell carcinoma of the cervix was evaluated. Twelve patients were stage I, 3 were stage II, 5 were stage III, and 4 were stage IV cervical carcinomas. Among the 24 patients, there were 4 complete and 8 partial responses (50%). The overall median response was 24 weeks. The overall cumulative survival was 55% at 40 weeks and 40% at 1 year after beginning this regimen. Complications included 4 patients who developed leukopenia, 3 thrombocytopenia, 11 stomatitis, 14 nephrotoxicity, 4 peripheral neuropathy, and 6 ototoxicity. The combination of cis-platinum and continuous infusion of 5-fluorouracil appears to have useful activity in patients with recurrent or metastatic squamous cell carcinoma of the cervix. PMID- 3338668 TI - The electrosurgical operation of vulvar carcinoma with postoperative irradiation of inguinal lymph nodes. AB - The results of treatment in the department of 607 patients with invasive squamous cell carcinoma of the vulva between 1952 and 1980 is described and analyzed. The absolute 5-year cure rate in these patients was 60.3%. Particular attention was given to lymph node status (TNM system) in the analysis of the last 141 patients treated. The absolute 5-year survival rate was 67% for the N0-N1 patients and 43% for the N2-N3 patients. Patients were treated uniformly by means of electrosurgical operation and postactinic irradiation of the inguinal lymph nodes. Operative lymphadenectomy was performed only in 5% of cases when the diameter of inguinal lymph nodes was greater than 2 cm. This simple surgical technique, in combination with irradiation of inguinal lymph nodes, gives excellent results and avoids the complications associated with inguinofemoral lymphadenectomy. Owing to its combination of electrosurgical operation of the vulva and irradiation of the inguinal regions as a standard procedure, the treatment involves extremely low strain on the patient and is almost free of complications. This seems to be particularly important as the results of our treatment are not less satisfactory than those of more aggressive procedures. PMID- 3338669 TI - Whole abdomen radiation for minimal residual epithelial ovarian carcinoma after surgical resection and maximal first-line chemotherapy. AB - Ten patients with Stage III epithelial ovarian received whole abdomen radiation therapy after extensive courses of chemotherapy and second or third laparotomies. All patients had less than 2-mm diameter residual disease. The major side effect was bone marrow suppression which led to decreased dose or field size in four patients. Five patients have recurred and three of these have died. Further treatment after recurrence was compromised by bone marrow suppression. While 40 50% of selected patients may respond to this approach, numerous alternatives are being explored that would not handicap further treatment to the same degree and may have equal response rates. PMID- 3338670 TI - DNA flow cytometry and morphometry as prognostic indicators in advanced ovarian cancer: a step forward in predicting the clinical outcome. AB - In 74 patients with advanced ovarian cancer, the value of DNA flow cytometry and morphometry was evaluated and compared with histological grading and clinical outcome. By means of both DNA flow cytometry and morphometry a clear distinction was found between a favorable group of 15 patients, with a median survival of more than 60 months, and the remaining patients, of whom the majority died during the same follow-up period. The levels of significance for DNA flow cytometry (P = 0.0002) and morphometry (P = 0.0001) with respect to survival of the favorable and unfavorable groups of patients were higher than for histological grading (P = 0.02). In a multivariate analysis it was demonstrated that morphometry proved to be the factor of most relevance for survival, although the effect of DNA flow cytometry was almost as good. Data such as presence of ascites, the size of the residual tumor mass, choice of chemotherapy, FIGO stage, and histological grade were not of additional prognostic relevance in this analysis. It is concluded that both morphometry and DNA flow cytometry are a step forward in identifying favorable and unfavorable groups of patients with advanced ovarian cancer. For the daily practice of management of ovarian cancer patients, morphometry may be an attractive support of visual grading. PMID- 3338671 TI - Serial D-dimer levels in the assessment of tumor mass and clinical outcome in ovarian cancer. AB - D-dimer (DD)--an end product of fibrinolysis--was measured in serum by enzyme immunoassay using a monoclonal antibody to the gamma gamma crosslink in patients with ovarian cancer, before primary surgery and during chemotherapy for 12 months or more. Serial DD levels were found to have a high sensitivity for the detection of tumor in patients with subclinical disease (91%) as well as for predicting progression of disease (100%). As determined by a careful second-look laparotomy in patients with complete clinical remission the DD marker was highly predictive of tumors less than 1 cm. The negative predictive value (82%) was higher than the positive predictive value (69%). However, there were 31% of the patients who showed a false-positive result; a close examination of the clinical data of these 9 patients failed to reveal an explanation for the positive DD levels. Despite the lack of specificity (50% in the present series), the findings support the use of DD in the assessment of patients with ovarian cancer, especially those with subclinical disease. PMID- 3338672 TI - Adriamycin and cisplatin in the treatment of stage III and IV epithelial ovarian carcinoma. AB - A total of 342 eligible, previously untreated patients with Stage III or IV epithelial ovarian carcinoma were treated with Adriamycin and cisplatin, both at 50 mg/m2, for nine courses. Of the 210 patients who had clinically detectable disease after initial surgery, 85 (41%) had a complete clinical response and 45 (21%) had a partial clinical response. A total of 197 were clinically free of disease at the completion of chemotherapy and 175 of these had a second-look laparotomy; 55 had no macroscopic or microscopic evidence of residual disease after multiple random biopsies were examined histologically (complete surgical/histologic response). The major determinants of complete surgical/histologic response were diameter of largest residual tumor prior to treatment, ECOG performance status, and grade, patients with grade 3 tumors having a higher complete response rate than those with grade 1 or 2 tumors. The major determinants of survival were ECOG performance status and diameter of largest residual tumor prior to treatment. Median survival of the total group was 1.8 years. PMID- 3338673 TI - Right ventricular metastasis of endometrial carcinoma: a case report. AB - Although between 5 and 20% of cancer deaths have cardiac metastasis at postmortem examination, pelvic malignancy is a seldom-reported primary source. Endometrial carcinoma rarely results in distant metastasis. A patient is described who presented with a large symptomatic right ventricular metastasis 15 months after a total abdominal hysterectomy and bilateral salpingo-oophorectomy for Stage I poorly differentiated adenocarcinoma of the uterine corpus. PMID- 3338674 TI - Malignant pericardial effusion in endometrial adenocarcinoma. AB - A case of endometrial adenocarcinoma in a 62-year-old woman with malignant pericardial effusion is presented. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic node dissection, and paraaortic node biopsy. Postoperatively, she was placed on a combination chemotherapy regimen of cisplatin, doxorubicin, and cyclophosphamide. The patient developed cardiac tamponade during the course of chemotherapy. Although we first suspected cardiotoxic effect of doxorubicin, cytologic examination revealed adenocarcinoma cells in the pericardial fluid. A review of the literature revealed no other cases of cardiac metastasis from endometrial carcinoma diagnosed during life. PMID- 3338675 TI - Normal pregnancy and delivery two years after adjuvant chemotherapy for grade III immature ovarian teratoma. AB - A 27-year-old woman with grade 3 immature teratoma of the ovary was treated with unilateral salpingo-oophorectomy and VAC combination chemotherapy. She received 6 postoperative courses, although initially 12 were planned. Chemotherapy had to be discontinued because of severe bone marrow toxicity. Eighteen months later the patient became pregnant and was ultimately delivered of a normal child. This is the second report of a successful pregnancy following VAC chemotherapy for immature teratoma. PMID- 3338676 TI - Ovarian mucinous cystadenocarcinoma of low malignant potential associated with a mature cystic teratoma. AB - A 54-year-old female underwent exploratory laparotomy for evaluation of a large abdominopelvic mass. She was found to have a 29-pound multicystic tumor arising from the right ovary. There were no other gross intraabdominal abnormalities. Histologic examination of the mass revealed a mucinous cystadenocarcinoma of low malignant potential and a mature cystic teratoma. To our knowledge, this is the first case report of an ovarian epithelial adenocarcinoma of low malignant potential associated with a mature cystic teratoma. PMID- 3338677 TI - Term pregnancy after three trophoblastic disease events. AB - A case of successful pregnancy following two hydatidiform moles and a choriocarcinoma, treated with the EMA-CO regime, is reported. This is the first reported successful pregnancy after administration of etoposide. PMID- 3338678 TI - Gliomatosis peritonei with endometriosis externa. AB - A case of gliomatosis peritonei developed 9 years after the removal of an immature ovarian teratoma is reported. An unique association of gliomatosis with endometriosis externa was found without the usual symptoms of endometriosis. The prognosis of gliomatosis is generally excellent and depends on the histological grade of the primary tumor and on the presence of organ metastasis or immature tumor elements in the implants. Pathogenetical aspects of both lesions are discussed briefly. PMID- 3338679 TI - The Second Indo-Pacific Congress on Legal Medicine and Forensic Science. August 14-18, 1986, Colombo, Sri Lanka. Part I. PMID- 3338681 TI - Sudden death in the chronic alcoholic. AB - A review of the causes of sudden death in 500 chronic alcoholics is presented. The deaths were fairly equally distributed between trauma, natural causes, acute intoxication and alcohol related disease. In a small but significant number, the cause is not initially clear although distinct patterns of death were evident. PMID- 3338680 TI - Pattern of acute poisoning in a medical unit in central Sri Lanka. AB - One hundred and seventy nine cases of acute poisoning constituting 1.1% of all admissions to the medical unit over 3 years were analysed. Eighty-three per cent of the patients were under 30 years of age and 72% were males. The common agents were: OP insecticides in 51%, kerosene oil in 12%, rat poison in 8% and drugs in 8%. Ingestion with suicidal intent was the common mode of poisoning. The overall mortality was 16%. The results from four other major centres in Sri Lanka are presented for comparison. PMID- 3338682 TI - The doctor and the court in Norway. PMID- 3338684 TI - Post-mortem examination and certification of death under G.D.R. law. AB - Post-mortem examination and certification of death in the G.D.R. are regulated by the Order on the Medical Post-mortem Examination (O.M.P.E.) issued in 1949 and confirmed in 1978. The tasks of the doctor certifying death are described as well as the co-operation between police, district attorney, and pathologist, and legal doctor, respectively, in all cases of death 'under suspicious circumstances.' Medical as well as judicial aspects of post-mortem examination are discussed. PMID- 3338683 TI - The course of alcoholism. Long-term prognosis in different types. AB - The disease concept of alcoholism was first introduced into the medical literature by Magnus Huss in 1984. Since that time many authors have attempted to define therapy-related sub-groups of chronic alcoholics but have been unsuccessful until now because alcoholism represents a complex development and becomes apparent in various clinical pictures. As the method of cross-sectional investigations does not seem to be able to produce reliable results, we performed a prospective long-term study of 444 alcoholics. The methodological claims in literature were taken into consideration like selection criteria, programmes and goals of therapy, follow-up rate and time, etc. Careful observation of the pertinent parts of the pathogenetic pathway leading to chronic alcoholism enabled the authors to establish 4 sub-groups of alcoholics relevant for treatment. PMID- 3338685 TI - Medical confidentiality. AB - Confidentiality in the medical relationship is an important, but by no means absolute, concept. It is a means by which the law protects the patient's privacy. But there are sometimes more important ideals than the protection of privacy. In order to determine whether confidentiality is to be recognised, the patient's interest in his privacy must be balanced with other potentially conflicting interests. Each legal system must determine for itself the weight to be given to any particular interest. PMID- 3338686 TI - Forensic medicine and human rights. AB - The forensic scientist is used to evaluate lesions with regard to their age, the weapon used, the seriousness, etc. Based on a material of examinations of alleged victims of torture some of the types of lesions are discussed. The importance of being strictly objective and using a scientific approach is stressed. The Committee of Concerned Forensic Scientists and Physicians for the Documentation of Human Rights Abuses (CCFS) was formed in 1984. The aims and the work of the committee are described. PMID- 3338687 TI - "Who is first on the scene?". AB - Forensic specialists are well standardised throughout the world and their opinions are respected by the courts. Doctors involved in the immediate clinical forensic assessment of persons in police custody are not, however, so well standardised. Some countries employ trained police surgeons or police medical officers, other countries rely on hospital interns, others simply accept the first doctor available. Can courts rely on their testimony? Can specialists depend on their skills? A call is made for such generalists to meet on an international basis to establish standards. PMID- 3338688 TI - Sequelae to torture. A controlled study of torture victims living in exile. AB - Twenty-eight Turkish refugees living in Denmark were examined by the authors in the period 1984-85. Fourteen of the persons alleged having been tortured in Turkey during the period 1980-83. The remaining 14 persons reported that they had not been tortured and thus acted as controls. All the testimonies were found valid according to a method previously used by us. The most common forms of violence reported were blows and electrical torture. Blindfolding, solitary confinement and threats were also frequent. At the time of examination the main mental complaints were sleep disturbances with nightmares and impaired memory. Emotional lability and concentration disturbances were also frequent. Physically the torture victims suffered from headache, various cardio-pulmonary and muscular pains, dyspepsia and reading disturbances. All reported that they had been healthy before torture. The clinical examination revealed only a few signs related to torture, although examples of minimal scars, fractured or missing teeth, discrete neurological disorders and mental depression were found. The 14 controls had significantly fewer complaints, and almost no abnormalities were found during the clinical examination. The present study clearly demonstrates the traumatic effects of torture. PMID- 3338689 TI - Forensic science and the law. AB - Forensic Science today makes an important contribution to the operation of the Criminal Justice System providing evidence which could help decide the guilt of a suspect. Forensic Science is able to do so because it has developed to operate within the reality determined by the Criminal Justice System. Changes that are occurring today seem to upset the relationship between Forensic Sciences and the Criminal Justice System by the creation of communication problems. Examples of these problems exist in the changes occurring in the concept of death made necessary by organ transplants. These changes have shifted the focus from the quantity of life to the quality of life and make it impossible for the Forensic Scientist to answer honestly the questions that might be put him. The need for reforms in the law in view of social changes has been recognized and in many countries attempts at such changes are afoot. With these changes a new reality is being defined. Forensic Science, being a discipline that comes first in contact with a multitude of emergent problems, has a part to play in the definition of this reality. PMID- 3338690 TI - A pathologist's view of terrorist violence. AB - The experience of the Northern Ireland State Pathology Service is drawn on to illustrate the forensic aspects of death by shooting and bombing caused by terrorists. The investigations into these deaths have to contend with rumours and allegations which can inflame feelings in the community or mislead the investigators and this aspect is dealt with. The conclusion is reached that when terrorist violence erupts there must be a forensic service able to cope and maintain the usual high standards of scientific investigation. PMID- 3338691 TI - Intoxication at home due to carbon monoxide production from gas water heaters. AB - Forensic medicine has a role to play in the community not only when dealing with criminal cases. When the forensic scientist observes fatalities that could have been prevented, he has an obligation to respond with the purpose of preventative measures. In a short period in Copenhagen there were a number of fatalities due to the production of carbon monoxide from gas water heaters. The gas water heaters were in most cases malfunctioning due to sooted convectors and installed without a flue, but at the time of installation maintenance checks were not mandatory, and if carried out they were often unprofessional. It is emphasized that even with well functioning equipment, the danger of intoxication exists when using a heater without a flue over an extended period, if the apartment is thoroughly insulated. The oxygen will then be used in the combustion and CO produced. The symptoms are insidious and uncharacteristic. Examples are described where physicians have failed to diagnose the condition in patients in adjoining apartments. The authorities finally responded to the medical reports with new regulations and with a favourable result. The responsibility with regard to the control of technical installations in a technically advanced society is discussed. PMID- 3338692 TI - Identification from skeletal remains. AB - The remains of a suspected case of homicide, found to be almost totally skeletal on exhumation, was dug out from a pit in a tract of marshy land in the deep south or Sri Lanka. No clothing or other identifying articles were found with the remains. During exhumation a distinct odour of kerosene oil was observed. Examination revealed that the major part of the skeleton was present, including the skull and lower jaw. Examination of these enabled an opinion to be given on the stature, sex and age of the deceased. The head hair found at exhumation showed evidence of burning. Two groups of injuries were found in the bones. One group was consistent with injuries caused during life and showing the characters of healing and moulding. Although medical records were not available, it was possible to obtain a description of the injuries from the court records as a doctor had given evidence on injuries sustained by the deceased years previously. The other group comprised of injuries that would have caused or contributed to death, or were post-mortem injuries inflicted for purposes of disposal. This case illustrates that personal identification may be established from old healed skeletal injuries. PMID- 3338694 TI - Analysis of fatalities in road accidents. AB - This paper is based on the analysis of 524 autopsies carried out on the victims of road accidents at the Office of the Judicial Medical Officer, Colombo for a 2 year period ending December 1985. 51.4% of the fatalities were among pedestrians. The highest number of fatalities were in the age group 20-29 years. Cranio cerebral injury was the commonest cause of death in all groups of victims. PMID- 3338693 TI - Agrochemical poisoning in Sri Lanka. AB - Mortality resulting from agrochemicals met within the Office of the Judicial Medical Officer, Colombo, which is the premier Medico-legal Institute in Sri Lanka, are analysed over a 3-year period and the morbidity and mortality rates of the entire country are examined over a 10-year period. The number of patients admitted to hospitals in Sri Lanka during the period 1975-1983, stood at around 11,000-15,000 each year, with the year 1983 recording 16,649 admissions. The number of deaths during the same period varied from 900 to 1500 each year, while the year 1983 recording 1521 deaths. About 75% of such cases of poisoning were due to self ingestion while accidental and occupational poisoning formed the balance. Principal agricultural districts like Kurunegala, Jaffna, Vavuniya, Nuwara-Eliya and Badulla recorded the highest incidence of poisoning. The mortality figures of the Office of the J.M.O., Colombo, indicated that 4% of all bodies subjected to autopsy were those of agrochemical poisoning. The male/female ratio was 2:1. Seventy-five percent of deaths from agrochemical poisoning were recorded in the 15-39 year age group, while 33% of deaths belonged to the 20-24 age group. One third of cases of agrochemical poisoning were dead on being brought to hospital, while 50% were dead within 2 h and 60% dead within 24 h. Organophosphates accounted for 57.6% of all cases of agrochemical poisoning, while paraquat accounted for 21.2% of cases. Deaths were also reported from what are called safe chemicals like Carbamates and Pyrethrums due to their lethal additives. PMID- 3338695 TI - Acute organophosphorus insecticide poisoning in Sri Lanka. AB - Records of 92 cases of acute organophosphorus (OP) insecticide poisoning were analysed. Of the patients 91% were under 30 years of age and 86% were males. The common agents were Dimethoate, Methamidophos, Malathion, Monocrotophos and Fenthion. Poisoning was due to ingestion with suicidal intent in the majority. In addition to the acute cholinergic features, the other important manifestations were delayed onset respiratory paralysis and delayed polyneuropathy. The overall mortality was 18%. PMID- 3338696 TI - Establishment of a new cell line from a woodchuck hepatocellular carcinoma. AB - A new cell line derived from a woodchuck hepatitis surface antigen-positive woodchuck hepatocellular carcinoma has been established and named T3-HEP-W1. This new cell line was established directly from a primary woodchuck hepatocellular carcinoma. Adaptation of the cells to the in vitro culture condition was completed after 3 months, with the doubling time of 24 hr. The morphologic features of the cell by light microscopy were of an epithelial type. The modal chromosome number was 100. Ornithine and tyrosine aminotransferase activities were detected. Production of albumin was negative. Integration of woodchuck hepatitis virus DNA was demonstrated by Southern blot analysis, although the secretion of woodchuck hepatitis surface antigen was not detected. T3-HEP-W1 is quite different from the previously reported WH257GE10 cell line and provides another in vitro model for the study of human hepatocellular carcinoma related to hepatitis B virus. PMID- 3338697 TI - Selective regulation of intrinsic membrane proteins in HepG2. AB - Expression of three hepatocellular membrane proteins--the asialoglycoprotein receptor (hepatic binding protein) the insulin receptor and organic anion binding protein--have been studied in the HepG2 cell line. HepG2 grown in minimal essential medium supplemented with 10% fetal bovine serum maximally expressed hepatic binding protein and insulin receptor only at confluence while organic anion binding protein appeared independent of the state of cellular proliferation. When cells were grown in medium supplemented with dialyzed fetal bovine serum, adult bovine serum or in chemically defined medium, expression of hepatic binding protein and insulin receptor but not organic anion binding protein was reduced by 60 to 80%. Immunoblotting techniques revealed that cells grown in dialyzed fetal bovine serum contained virtually no mature, glycosylated 45 kD hepatic binding protein, but a small amount of 36 kD protein. Metabolic labeling of cells grown in dialyzed fetal bovine serum with [35S] methionine indicated reduced synthesis of the 45 kD hepatic binding protein and the absence of the 36 kD protein. Restoration of normal expression of hepatic binding protein and insulin receptor was achieved by addition to dialyzed fetal bovine serum of: fetal bovine serum; 2,000 dalton ultrafiltrate of fetal bovine serum, or 300 to 350 dalton fraction of the ultrafiltrate. The normal concentration of organic anion binding protein demonstrable in cells grown in dialyzed fetal bovine serum indicates that the low molecular weight factor(s) is not a generalized modulator of plasma membrane biogenesis. However, its effect on the steady-state level of the hepatic binding protein and insulin receptor, characteristic of mature hepatocytes, suggests a role for this fetal serum factor in hepatocellular differentiation. PMID- 3338698 TI - Microsomal specificity underlying the differing hepatic formation of bilirubin glucuronide and glucose conjugates by rat and dog. AB - Bilirubin monoglucuronide monoglucoside diester is one of the principal bilirubin conjugates in dog bile (and a lesser conjugate, in human bile), and bilirubin diglucoside is an occasional trace conjugate in dog bile whereas, in contrast, neither is detectable in rat bile. In order to investigate, in comparative fashion, the factors underlying the formation of glucuronide and glucose containing conjugates, hepatic microsomes were isolated by differential centrifugation from the livers of both normal mongrel dogs and Sprague-Dawley rats, and their formation of bilirubin conjugates examined, in the presence of varying levels of UDP-glucuronate and UDP-glucose. Bilirubin and its conjugates were extracted and separated by high-performance liquid chromatography; a new methodology was devised, which clearly separates bilirubin diglucoside from bilirubin monoglucuronide, as well as bilirubin diglucuronide, the mixed monoglucuronide monoglucoside conjugate and bilirubin monoglucoside. At bilirubin levels of 12.5 microM, in the presence of equal amounts of both UDP-glucuronate and UDP-glucose, dog microsomes formed substantial amounts of both bilirubin diglucuronide and the mixed monoglucuronide-monoglucoside conjugate, and minor amounts of bilirubin monoglucuronide and bilirubin diglucoside. Microsomes from rat liver, under similar conditions, formed only bilirubin diglucuronide and bilirubin monoglucuronide. When only UDP-glucose was present, dog microsomes formed predominantly diglucoside and rat, predominantly monoglucoside. The findings imply that it is not the availability of the UDP-glycoside but rather the preference of the microsomal enzymic system for the different glycosidic nucleotides which dictates the varieties of bilirubin conjugates ordinarily formed in these two species. PMID- 3338699 TI - Correlation between the biliary excretion of ouabain and the lateral mobility of hepatocyte plasma membrane proteins in the rat--the effects of age and spironolactone pretreatment. AB - The biliary excretion of intravenously injected ouabain and the diffusion constant of the lateral mobility of hepatocyte plasma membrane proteins were examined in control (saline-treated) and spironolactone-treated Wistar male rats of different ages (4, 14 to 15 and 24 months old). The biliary excretion of ouabain progressively decreased with age in control rats, the first 10-min biliary recovery in 24-month-old animals being one-third that of the youngest rats (4-month-old). The oral administration of spironolactone for 4 days (10 mg per 100 gm body weight on the first day and 20 mg per 100 gm body weight for the successive 3 days) caused a marked increase in the biliary recovery of ouabain in all age groups. Similarly, the average lateral diffusion constant of hepatocyte plasma membrane proteins as measured by fluorescence recovery after photobleaching showed a linear decrease with age, as was previously observed with F-344 rats of both sexes. Markedly and significantly (30 to 40%) higher diffusion constants were observed in rats pretreated with spironolactone for all three age groups, compared with the respective control values of corresponding ages. The parallelism between ouabain excretion and protein diffusion (i.e., a decrease with age and an increase with spironolactone pretreatment) suggests that the lateral mobility of proteins in the hepatocyte plasma membrane is a candidate mechanism for regulating ouabain excretion through the liver into the bile, most probably by regulating the hepatic uptake process for ouabain. PMID- 3338700 TI - Validation of viscosity measurements for canine hepatic bile. AB - This study developed the validated standards for a known viscosity method by obtaining consistent viscosity measurements with defined precision, reproducibility and sensitivity limits for canine hepatic bile. Size 75 Cannon Manning semimicro viscometers yielded the most precise viscosity measurements. With the development of proper handling methods for fresh bile samples, a precision defined by a coefficient of variation of less than or equal to +/- 0.3% was obtained. To maintain viscometer constancy, the viscometers must be cleaned with chromic acid after each bile test and pass reproducibility tests using defined distilled water viscosity tests. PMID- 3338701 TI - Impaired release of vitamin A from liver in primary biliary cirrhosis. AB - In 44 patients with primary biliary cirrhosis serum levels of vitamin A, retinol binding protein and transthyretin (prealbumin) were found to be significantly lower than in 25 sex- and age-matched controls. Liver biopsies were available for chemical analyses in 28 of the patients. Their mean liver vitamin A concentration (2.8 +/- 2.0 mumoles per gm wet weight) did not differ significantly from that in 22 cases of sudden death which served as controls (2.0 +/- 1.5 mumoles per gm wet weight). Immunohistochemical investigation showed a normal distribution of serum retinol-binding protein in the patients' livers, whereas the staining pattern of cellular retinol-binding protein, believed to be involved in the intrahepatic transport of vitamin A, was abnormal. Thus, the number size and cellular retinol binding protein staining intensity of fat-storing (Ito) cells were clearly higher in the patients as compared with controls. The results suggest that the low serum vitamin A levels in primary biliary cirrhosis are not a consequence of vitamin A deficiency but instead reflect a defective mobilization of vitamin A from the liver. PMID- 3338702 TI - Serum hyaluronate in primary biliary cirrhosis--a biochemical marker for progressive liver damage. AB - To evaluate serum hyaluronate as a marker for progressive liver injury in patients with primary biliary cirrhosis, a longitudinal study including 48 patients was conducted with a mean follow-up time of 40 months. The patients were examined every 6 months with a standardized set of conventional liver function tests, and a liver biopsy was performed every year. The hyaluronate concentration correlated significantly (p less than 0.001) with albumin, t1/2 galactose tolerance test, bilirubin and prothrombin time but not to serum variables reflecting inflammatory activity. Furthermore, there was a close correlation between serum hyaluronate levels and histopathological changes in the liver. The hyaluronate concentration increased significantly over time in all clinical stages of primary biliary cirrhosis (p less than 0.01), whereas the conventional liver function tests only changed in the advanced cases. The present data indicate that serum hyaluronate may be a sensitive marker for progressive liver damage in primary biliary cirrhosis. Serial determinations of hyaluronate are therefore of potential value for monitoring liver function during clinical management of the condition. PMID- 3338704 TI - Spontaneous bacterial peritonitis: an explosion of information. PMID- 3338703 TI - Hepatofugal portal flow in cirrhosis: observations on hepatic hemodynamics and the nature of the arterioportal communications. AB - Six of 85 patients (7%) with alcoholic liver disease undergoing transhepatic portal pressure measurement had either stagnant (3 patients) or reversed (3 patients) portal blood flow documented by gentle hand injection of 1 to 2 ml of angiographic contrast. Portal blood flow was uniformly hepatopetal in 24 patients with nonalcoholic liver disease. Recurrent spontaneous hepatic encephalopathy and sodium retention occurred in 4 of 6 patients with stagnant or reversed portal flow; gastrointestinal bleeding was not seen. Standard laboratory tests of liver function were widely variable. Net portal pressure was lower in this group than in patients with alcoholic liver disease and forward portal flow (9.2 +/- 2.6 vs. 15.6 +/- 4.1 mm Hg, p less than 0.001). Wedged hepatic vein pressure was 1 to 7 mm Hg higher than portal vein pressure in patients with reversed portal flow. The arterioportal extraction of bile acid was calculated from the difference in concentration between artery and portal vein, and total functional hepatic blood flow was calculated from the hepatic extraction and systemic clearance of indocyanine green. Extraction was 0%, and hepatic blood flow was 0.469 liter per min in a patient with hepatofugal portal flow and recurrent encephalopathy. Extraction was 20%, and hepatic blood flow was 4.014 liters per min in a patient who had never had encephalopathy. These data indicate that arterioportal communications may be sinusoidal or presinusoidal in patients who lose forward portal flow and that the amount of flow in the arterioportal circuit, together with its efficiency, largely determine the clinical outcome. PMID- 3338705 TI - Oral charcoal therapy of congenital erythropoietic porphyria. PMID- 3338706 TI - Hepatic sublobular synthesis of urea: control by oxygen or by pH gradient? PMID- 3338707 TI - Persistent measles virus genome in autoimmune chronic active hepatitis: cause or coincidence? PMID- 3338708 TI - Reye's syndrome: are adults big children? PMID- 3338709 TI - Primary biliary cirrhosis and the CREST syndrome: new terminology? PMID- 3338711 TI - Understanding noncirrhotic portal hypertension: menage a fois. PMID- 3338710 TI - Preoperative endoscopic sphincterotomy as an adjunct to cholecystectomy for common bile duct stones. PMID- 3338712 TI - Asymptomatic patients. PMID- 3338713 TI - Focal infiltrations of polymorphonuclear leukocytes in liver biopsies: traumatic lesions? PMID- 3338714 TI - Levamisole therapy in chronic type hepatitis. PMID- 3338715 TI - Mevalonic aciduria. PMID- 3338716 TI - Molecular determination of the primary biliary cirrhosis-specific M2 antigen. PMID- 3338717 TI - Interrelationship between splenic and superior mesenteric venous circulation. PMID- 3338718 TI - Iron metabolism in the erythrophagocytosing Kupffer cell. AB - Like the peritoneal macrophage, the isolated Kupffer cell is capable of processing and releasing iron acquired by phagocytosis of immunosensitized homologous red blood cells. When erythrophagocytosis is restrained to levels which do not affect cell viability, or less than 1.5 red cells/macrophage (phagocytic index of 150%), over 40% of iron acquired from red cells is released within 24 hr. More active erythrophagocytosis results in greater release of iron but progressive deterioration in cell viability. Iron release is temperature dependent, the rate at 37 degrees C being nearly 5-fold greater than at 4 degrees C. Inclusion of either desferrioxamine or apotransferrin in the culture medium augments iron release by 25 to 30%, with both agents together having an almost additive effect. Despite its effect on iron release, apotransferrin is not found in sonicates of Kupffer cells, while desferrioxamine appears to chelate iron within the cells. Ascorbate also enhances iron release, but at the expense of cell viability. Neither chloroquine nor colchicine at concentrations which do not affect cell viability influence iron release. The inflammatory state, characterized by hypoferremia due to impaired processing or release of iron by the reticuloendothelial system, may be modeled in vitro when serum from rats bearing turpentine-induced abscesses is included in the culture medium. Attempts to delineate the humoral agent responsible for this effect have not been successful, iron release being insensitive to the presence of interleukin-1, gamma-interferon and tumor necrosis factor. PMID- 3338719 TI - Hepatic adenine nucleotide metabolism measured in vivo in rats fed ethanol and a high fat-low protein diet. AB - Rats fed a diet high in fat and low in protein continuously infused by intragastric cannula were given ethanol for 2 to 6 months in order to examine the response of liver adenine nucleotides to changes in systemic PO2. Hepatic adenine nucleotides were measured in vivo monthly using liver obtained by biopsy from rats while a high blood alcohol level was maintained. Ethanol decreased hepatic ATP and the total adenylate pool, but did not change the levels of ADP and AMP. Adenylate energy charge showed only a tendency to be decreased. Carotid arterial PO2 was mildly but significantly lower in ethanol-fed rats compared to the pair fed controls. Pure O2 inhalation for 3 min increased the PO2 four times in the ethanol and control-fed rats, and tended to increase ATP and decrease ADP in ethanol-fed rats as well as pair-fed controls. It restored the energy charge to a normal level in the ethanol-fed rats. Ten per cent O2 + 90% N2 inhalation for 3 min decreased the PO2 to 40 mm Hg in both the ethanol-fed and control rats, and this rapidly decreased ATP. This effect was significantly greater in the ethanol fed rats compared to the controls. The total adenylate pool and the energy charge were decreased only in ethanol-fed rats. The results show that the reduced energy stores in the rat liver induced by ethanol are rapidly responsive to changes in PO2. Thus, the livers of ethanol-fed rats were more vulnerable to transient hypoxia than were controls. PMID- 3338720 TI - 16,16-Dimethyl prostaglandin E2 delays collagen formation in nutritional injury in rat liver. AB - Chronic nutritional injury was induced in rats by a high-fat, lipotrope-deficient diet. The hepatoprotective effect of 16,16-dimethyl prostaglandin E2 on the deposition of collagen and fat was assessed by histological evaluation and measurement of hydroxyproline. Dose-response studies established that optimal protection was achieved by the twice daily administration of 16,16-dimethyl prostaglandin E2 at 100 micrograms per kg (subcutaneous) or 250 micrograms per kg (oral). 16,16-Dimethyl prostaglandin E2 and a crystalline analog [(p acetamidobenzamido)phenyl ester of 16,16-dimethyl prostaglandin E2 significantly delayed both the deposition of collagen and the increase in hepatic hydroxyproline content. There was an excellent correlation between the histological assessment of collagen and the biochemical measurement of hydroxyproline. These data provide a rationale for the evaluation of prostaglandins in the treatment of human liver disease. PMID- 3338721 TI - S-adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis. AB - We have measured the activity S-adenosyl-L-methionine synthetase in liver biopsies from a group of controls (n = 17) and in 26 cirrhotics (12 alcoholic and 14 posthepatic). The activity of this enzyme was markedly reduced in the group of cirrhotics (285 +/- 32 pmoles per min per mg protein) when compared with that observed in controls (505 +/- 37 pmoles per min per mg protein). No differences in S-adenosyl-L-methionine synthetase was observed between both groups of cirrhotics. Similarly, a marked reduction in the activity phospholipid methyltransferase was also observed in liver biopsies from the same group of cirrhotics (105 +/- 12 pmoles per min per mg protein) when compared with the control subjects (241 +/- 13 pmoles per min per mg protein). Again, no difference in the activity of this enzyme was observed between both groups of cirrhotics. These results indicated a marked deficiency in the metabolism of S-adenosyl-L methionine in cirrhosis. PMID- 3338722 TI - Is the hypotension of cirrhosis a GABA-mediated process? AB - Systolic and diastolic blood pressures were recorded in 176 ambulant patients with chronic liver disease, including 36 patients with compensated cirrhosis (Group I), 119 patients with noncirrhotic chronic liver disease (Group II) and 21 patients with benign structural or functional liver disease (Group III). Group I patients had significantly lower systolic (113.0 +/- 2.2 mm Hg, mean +/- S.E.) and diastolic (65.3 +/- 1.7 mm Hg) pressures than Group II patients (125.8 +/- 3.5 and 76.6 +/- 1.5 mm Hg, respectively (p less than 0.0001) or Group III patients (125.1 +/- 3.4 and 77.5 +/- 2.4 mm Hg, respectively) (p less than 0.0001). Serum levels of GABA, a potent amino acid neurotransmitter with known vasodilatory effects in vitro, were higher in Group I patients (1.12 +/- 0.26 microM, mean +/- S.E.) than in Group II patients (0.41 +/- 0.05 microM) (p less than 0.005) or Group III patients (0.34 +/- 0.03 mM) (p less than 0.05). A constant infusion of GABA into the systemic circulation of six adult dogs, at rates required to achieve serum GABA levels within one order of magnitude of those observed in humans with cirrhosis, resulted in a 17.0 +/- 4.3 mm Hg decrease in systolic pressure (p less than 0.05) and a 10.8 +/- 3.7 mm Hg decrease in diastolic pressure (p less than 0.05). Control amino acids were not vasoactive. The results of this study suggest that, in addition to other vasoactive compounds, a GABA-mediated process might contribute to the hypotension observed in patients with compensated cirrhosis. PMID- 3338724 TI - AIDS, psychiatry, and the law. PMID- 3338723 TI - The application of a numerical scoring system for evaluating the histological outcome in patients with chronic hepatitis B followed in long-term. AB - A numerical scoring system was applied and compared with conventional histological classification to assess the histological outcome in 42 patients with chronic hepatitis B followed for 16 to 162 months (mean = 75 months). Four histological categories in the biopsies were assessed and scored: (i) piecemeal necrosis; (ii) lobular necrosis; (iii) portal inflammation, and (iv) fibrosis and cirrhosis. The sum of all four categories was defined as the "Histological Activity Index." Altogether, 102 liver specimens, including 2 to 4 repeats from each patient, were investigated. A good correlation was noted between a high value of the Histological Activity Index score and several liver histology as monitored by conventional terminology for chronic hepatitis. Among patients with HBeAg persistence, 8 of 14 (57%) deteriorated during follow-up as judged by an increase in the Histological Activity Index score compared to 3 of 13 (23%) of the patients with HBeAg seroconversion (0.5 less than p less than 0.1). Piecemeal necrosis has been postulated to be a predictive marker for the eventual development of cirrhosis. Here, we found that a low score for piecemeal necrosis in the initial liver biopsy was significantly less predictive of a high fibrosis score in the follow-up biopsy than was a high score for initial piecemeal necrosis (p less than 0.001). It is concluded that the scoring system used can be applied to monitor the histological long-term follow-up, especially when separated into its four constituent categories. It also offers a means of predicting a chronic hepatitis outcome. PMID- 3338725 TI - Schizophrenic woman on neuroleptic medication suffers secondary depression. PMID- 3338726 TI - Housing the homeless mentally ill: a longitudinal study of a treatment approach. AB - In a one-year study of 49 homeless chronic mentally ill patients, the subjects, selected at admission for inpatient treatment, were randomly assigned to one of two groups. One group was placed in an experimental residential treatment program following discharge, and the other group received standard postdischarge care. Subjects were interviewed every four months during the year as well as at index hospitalization and discharge. Although the study remains exploratory due to the small sample size and case attrition, the authors found that compared with the control group, the subjects in the residential treatment program spent significantly more nights in adequate shelter, spent fewer nights in hospitals or undomiciled, and were more satisfied with and committed to their living arrangements. PMID- 3338727 TI - Criminal activity among the homeless: a study of arrests in Baltimore. AB - To illuminate the role of criminal activity among the homeless, particularly the homeless mentally ill, the author compared 634 arrests of homeless persons with 50,524 arrests in the general population that were made in Baltimore in 1983. Significant differences were found in the demographic characteristics of the two groups of arrested persons and in the types of offenses prompting the arrests. Among the homeless, those arrested were more likely to be male, white, and over age 45 and to have committed trivial, victimless crimes. Evidence suggests that ostensibly serious offenses such as assault, larceny, and burglary charged to homeless persons tended to involve petty thievery, entry into vacant buildings, and other acts aimed at maintaining subsistence in the absence of housing. PMID- 3338728 TI - Arrest rates among young adult psychiatric patients treated in inpatient and outpatient settings. AB - Within a statewide random sample of 611 young adult patients who received public inpatient, outpatient, and community residential care, 38 percent were found to have been arrested at least once in their adult lifetimes. Thirty-five percent had been arrested for felonies and 18.9 percent for violent crimes. Analyses by five major diagnostic groups showed that patients with a primary diagnosis of drug or alcohol abuse had the greatest overall frequency of arrests and also the greatest frequency of arrests for burglary, offenses against public order such as peace disturbance or loitering, and probation and parole violations. No significant differences between diagnostic groups were found for arrests for violent crimes. Characteristics that predicted which patients would be arrested in the year after receiving mental health services were a greater number of lifetime felony arrests, younger age, being black or a member of another minority group, and more years since first receiving public mental health care. PMID- 3338729 TI - Risk for depression in families over time: a pilot epidemiologic study. AB - A random sample of 34 families from the general population were studied over a 15 month period to determine their risk for depression over time. Adults and children in the families were interviewed three times during the 15-month period. Risk for depression was evaluated using four screening instruments, including the Diagnostic Interview Schedule. At the original interview, 40 percent of the families contained one or more members at risk for depression. The 15-month family incidence rate for risk for depression was 26 percent and of continued good mental health 74 percent. The mental health status of 35 percent of the families changed during the 15-month period, suggesting that longitudinal studies can provide a more accurate profile of family mental health than studies of families at a single point in time. PMID- 3338730 TI - Mental health staff and patient's relatives: how they view each other. AB - As part of a project to better serve the needs of patients' families, a New York state psychiatric facility surveyed 350 inpatient and outpatient staff and 250 family members about their attitudes toward each other and about the role of families in the patients' treatment. Generally staff felt positively about families and believed they should be meaningfully involved in the patients' treatment, but 61 percent reported spending less than one hour per week in contact with families. Staff cited conflict among themselves about the role of families and lack of time as the greatest impediments to interacting with families. Most families felt staff were supportive of them, but only 19 percent said staff provided them with enough information. Less than 21 percent had been invited to treatment planning meetings or to discharge conferences. The center is currently implementing training programs and administrative changes intended to increase cooperation between staff and patients' families. PMID- 3338731 TI - Capitation financing for the chronic mentally ill: a case management approach. AB - The method chosen for financing mental health care has profound implications for how that care will be delivered. Fee-for-service methods of reimbursement impede the implementation of certain essential program components. Capitation financing, in contrast, holds the promise of promoting an integrated system of care for chronic mental patients. The authors present data from a case management program that incorporates capitation financing. Discussion focuses on factors that planners need to consider when instituting a capitated financing system. PMID- 3338732 TI - What's in a diagnosis--and what isn't? PMID- 3338733 TI - A study of whether uniforms help patients recognize nurses. PMID- 3338734 TI - Using infrared scanning to decrease nighttime falls on a psychogeriatric unit. PMID- 3338735 TI - Planning a psychiatric intensive care unit. PMID- 3338736 TI - Challenges for trustees. PMID- 3338737 TI - Consistent care. PMID- 3338738 TI - Should private insurance be made mandatory? PMID- 3338739 TI - Grim outlook for profitability in 1988. PMID- 3338740 TI - Cash-flow problems worsening: survey. PMID- 3338742 TI - Care givers: generations of opportunities. PMID- 3338741 TI - Inflationary pressures grow, margins fall. PMID- 3338743 TI - Survey spots the tight turns in MD-CEO relations. PMID- 3338744 TI - Quality is still the top concern of coalitions. PMID- 3338746 TI - What's the top MD recruitment incentive? PMID- 3338745 TI - U.S. MD glut limits demand for FMG physicians. PMID- 3338747 TI - Quality could mean dollars for hospital labs. PMID- 3338748 TI - Are patients catching on to credit cards? PMID- 3338749 TI - Incentive plans hold increasing lure for multis. PMID- 3338750 TI - Insurer venture is managed care entry for AmHS. PMID- 3338751 TI - Collaborative practice benefits nurses, patients. PMID- 3338752 TI - Americans accept foreign-born physicians. PMID- 3338753 TI - Partial methods won't heal the health system. PMID- 3338754 TI - The macroeconomic vision of cost containment. PMID- 3338755 TI - More cuts in teaching-hospital payment. PMID- 3338756 TI - '87 financing activity reflects odd market. PMID- 3338758 TI - Medical malpractice issue tops state agendas. PMID- 3338757 TI - Bond volume rises: will Congress notice? PMID- 3338760 TI - Advertising focus may shift back to basics. PMID- 3338759 TI - Liposuction's popularity spells risks. PMID- 3338761 TI - Is the bloom off the rose of advertising? PMID- 3338762 TI - Physician marketing continues. PMID- 3338763 TI - Arizonans square off on HMO guaranty funds. PMID- 3338764 TI - Aging physical plants: holdovers from another era? PMID- 3338765 TI - Rural-urban distinction challenged in Missouri. PMID- 3338766 TI - Prenatal care education ensures healthy future. PMID- 3338767 TI - Automation is key to alternative delivery. PMID- 3338768 TI - Price prediction: no unusual increases. PMID- 3338769 TI - Neuroscience: your next center of excellence? PMID- 3338770 TI - Does public opinion influence tax status? PMID- 3338771 TI - Radiology system improves care. PMID- 3338772 TI - Equicor's data make a splash--but who cares? PMID- 3338773 TI - Analyst says more multis will form REITs. PMID- 3338774 TI - Economic development means patient days. PMID- 3338776 TI - Outbound telemarketing: the next wave? PMID- 3338775 TI - Mortality data shape a new marketplace. PMID- 3338777 TI - CEOs and the media strive for balance. PMID- 3338778 TI - Are HMOs slamming the door on psych treatment? PMID- 3338779 TI - States judge expert witnesses before they testify. PMID- 3338781 TI - CAP laboratory standard leads to controversy. PMID- 3338780 TI - Corporate CEOs don't want to pay for AIDS. PMID- 3338783 TI - Administrative fees controversy continues. PMID- 3338782 TI - Multis putting more effort into MD relationships. PMID- 3338784 TI - Multis sweep cash, boost investment income. PMID- 3338785 TI - Multis move to centralize IS decisions. PMID- 3338786 TI - Compensation must be tied to strategic goals. PMID- 3338787 TI - Health insurance satisfaction tied to cost. PMID- 3338788 TI - HR professionals: get close to the "gods". PMID- 3338789 TI - Absence of charge variants in human skeletal muscle enzymes of the glycolytic pathway. AB - Phenotypes of various glycolytic enzymes were determined in muscle biopsies. The results suggest that genetic effects on maximal enzyme activities may be associated with regulatory elements of the appropriate genes. PMID- 3338790 TI - Trichothiodystrophy, xeroderma pigmentosum and PIBI(D)S syndrome. PMID- 3338791 TI - Beta-thalassemia mutations in the Portuguese population. AB - In this study we have carried out haplotype analysis on the beta-globin gene cluster and characterized the beta-thalassemia mutation by oligonucleotide hybridization in 14 patients with thalassemia major and 5 with sickle cell/beta thalassemia originating from southern Portugal. We found that three mutations, namely the beta(0)-39, beta(0) IVS-1 nt 1 and beta(+) IVS-1 nt 110 are prevalent accounting for 53%, 32% and 10% of the beta-thalassemia chromosomes respectively. In general each mutation was associated with a specific chromosomal haplotype; the beta(0)-39 mutation, however, was linked to three different haplotypes. These results indicate that three oligo-probes complementary to the most common mutations allow prenatal diagnosis by oligonucleotide analysis in 96% of the couples at risk of having offspring with thalassemia major in southern Portugal. PMID- 3338792 TI - Genetic transferrin types and iron-binding: a comparative study of a European and an African population sample. AB - Two population samples, one from Europe and one from Africa, were analyzed for the distribution of genetic transferrin (TF) types, serum concentrations of TF, serum iron concentrations and free iron-binding capacities. In Europeans the distribution of the TF alleles was C1 = 0.816, C2 = 0.143, C3 = 0.037, and B2 = 0.004. In black Africans the allele frequencies were: C1, 0.823; C2, 0.104; and D1 = 0.073; TFC3 was absent. The mean serum concentrations were 362 +/- 88 mg/dl in Europeans and 528 +/- 176 mg/dl in Africans; this difference was statistically significant. The concentration of serum immunoglobulins was also elevated in black Africans although their health was reported to be normal. The serum iron concentrations in Africans were decreased; the free iron-binding capacity of TF was, thus, increased. In both population samples there was a tendency for slightly higher TF concentrations in the TF C1 subtype than the TF C2 subtype. This correlation was not statistically significant. Analysis of a larger sample is required to establish this relationship. PMID- 3338793 TI - Molecular basis of beta thalassemia in south China. Strategy for DNA analysis. AB - The phenotype of beta thalassemia can be caused by over 40 different mutations. To set up a prenatal diagnosis program using DNA analysis, it is important to determine the type and frequency of mutation in a particular geographic area. We have delineated the molecular lesions that cause beta thalassemia in the Guangdong province of China, and found six mutations in four different haplotypes. The surprising finding that five of these mutations each occur in two different haplotypes suggests the occurrence of crossing over or gene conversion events at the beta-globin locus. The delineation of the haplotypes and mutations will permit the choice of the appropriate probes for prenatal detection of beta thalassemia in this part of China. PMID- 3338794 TI - Fanconi's anaemia: correlation of genetic complementation group with psoralen/UVA response. AB - The correlation found by Moustacchi (1987) between cellular response to a crosslinking challenge and genetic heterogeneity in Fanconi's anaemia is confirmed for an earlier set of complementation groups (Zakrzewski and Sperling 1980). This allows the matching of the two independently established complementation groupings and better characterization of their DNA repair-related biochemical properties. PMID- 3338795 TI - A disease with features of cutis laxa and Ehlers-Danlos syndrome. Report of a mother and daughter. AB - A mother and daughter are described with light and electron microscopic, and biochemical abnormalities of their connective tissue characteristic of both cutis laxa and the Ehlers-Danlos syndrome. The mother was clinically normal, while her 8-year-old daughter exhibited loose, wrinkled skin and other clinical features of cutis laxa, and also fragility, bruisability and hyper-extensibility of the skin and poor healing of wounds, leaving "cigarette paper" scars, features characteristic of the Ehlers-Danlos syndrome. Light and electron microscopic studies of skin biopsy specimens and cultured skin fibroblasts from both individuals revealed reduced and distorted elastic fibres, a finding usually seen in cutis laxa. Electrophoretic studies of collagen excreted from cultured skin fibroblasts revealed in both individuals an alpha 2(I) chain with a molecular size smaller than usual. The father and elder daughter were normal by clinical, light and electron microscopic and electrophoretic studies. It was concluded from these findings that the mother and daughter represented a hitherto undescribed disease of the connective tissue with dominant inheritance and variable expressivity. PMID- 3338796 TI - Localization of the spherocytosis gene to chromosome segment 8p11.22----8p21. AB - A case of hereditary spherocytosis (HS) is reported. Cytogenetic study revealed a de novo minute deletion of chromosome 8. The critical portion which affected the expression of the HS phenotype appeared to be localized to 8p11.22----8p21.1. PMID- 3338798 TI - G6PD Viangchan: a new glucose 6-phosphate dehydrogenase variant from Laos. AB - We describe a previously unreported glucose-6-phosphate dehydrogenase-(G6PD) variant. G6PD Viangchan was found in a Laotian immigrant to Calgary, Canada, and was characterized by severe enzyme deficiency, normal electrophoretic mobility, increased pH optimum, and abnormal kinetics for the natural substrates G6PD and NADP, as well as the artificial substrates 2-deoxy G6PD and deamino NADP. The inhibition constant for NADPH was decreased. The subject has no evidence suggesting chronic or episodic hemolysis. PMID- 3338797 TI - Assignment of the human progesterone receptor to the q22 band of chromosome 11. AB - The human progesterone receptor gene was localized by in situ hybridization to the q22 band of chromosome 11. PMID- 3338799 TI - Population cytogenetics of rare fragile sites in Japan. AB - A population cytogenetic study of three groups of rare fragile sites defined in Human Gene Mapping 8 (HGM8, Berger et al. 1985) has been conducted using peripheral blood lymphocytes of healthy Japanese subjects. We have examined 1,022 blood donors for folate-sensitive and bromodeoxyuridine (BrdU)-requiring, and 845 for distamycin A-inducible fragile sites. Out of 17 rare autosomal fragile sites defined in HGM8, the following six were identified in Japan; folate-sensitive fra(2)(q11), fra(11)(q13) and fra(11)(q23), distamycin A-inducible fra(16)(q22) and fra(17)(p12), and BrdU-requiring fra(10)(q25). The incidences of distamycin A inducible fra(16)(q22) (1.42%) and fra(17)(p12) (3.08%) were considerably higher than those of the other sites in Japan. Furthermore, a folate-sensitive fra(17)(p12) and a distamycin A-inducible fra(8)(q24.1) have been newly found in the present study. Their incidences were 0.10% (1/1,022) and 0.71% (6/845), respectively. Since the expression of this fra(17)(p12) was induced by fluorodeoxyuridine, suppressed by thymidine, but not induced by distamycin A, it can be classified as a folate-sensitive site. The expression of the new distamycin A-inducible fra(8)(q24.1) was also enhanced by treatment with Hoechst 33258, berenil and 4',6-diamidino-2-phenylindole (DAPI). This fragile site fulfils all four classical criteria suggested by Sutherland (1979) and also new criteria for a rare fragile site defined in HGM8 (Berger et al. 1985). PMID- 3338801 TI - Investigation of three XX males by cytogenetic and DNA analyses. Suggestion of Y chromosome inversion polymorphism. AB - We report cytogenetic and DNA studies in three XX males. Two males seemed to have extra chromosomal material on the tip of one X chromosome. All three males were shown to have Y chromosome material as indicated by hybridization of Y-specific DNA probes to genomic DNA. One male was unusual in that as he showed the 15-kb fragment detected by pDP34 that is thought to map close to the Y centromere. It is suggested that this finding might point to an inversion on the Y chromosome. PMID- 3338802 TI - A BrdU-requiring fragile site on chromosome 12. AB - A BrdU-requiring fragile site, fra(12)(q24.2), on human chromosome 12 of some individuals is reported. This fragile site is inherited in a Mendelian codominant fashion and does not seem to be associated with any physical or mental abnormality in carriers. It was mostly observed as a chromatid gap: no acentric fragments, triradials or deleted chromosomes were found. The fra(12)(q24.2) was expressed in 34%-48% of metaphases in lymphocyte cultures from carriers when BrdU and FdU were added 6.5 h before harvest, while the expression ranged between 5% and 20% when the cultures were treated with BrdU alone. The fra(12)(q24.2) represents the second BrdU-requiring rare fragile site described on human chromosomes. PMID- 3338803 TI - The position of the gene locus for monocyte alloantigens (HMA system) on chromosome 6. AB - In ten families with 65 children (with 64 informative meioses), a close linkage between the monocyte antigen locus (HMA) and HLA was found with a recombination frequency of 1.56%. PMID- 3338800 TI - The CpG dinucleotide and human genetic disease. AB - Reports of single base-pair mutations within gene coding regions causing human genetic disease were collated. Thirty-five per cent of mutations were found to have occurred within CpG dinucleotides. Over 90% of these mutations were C----T or G----A transitions, which thus occur within coding regions at a frequency 42 fold higher than that predicted from random mutations. These findings are consistent with methylation-induced deamination of 5-methyl cytosine and suggest that methylation of DNA within coding regions may contribute significantly to the incidence of human genetic disease. PMID- 3338804 TI - Frequency of tri- and multiradial configurations in fragile X chromosomes. AB - The appearance of tri- or multiradial configurations in fragile chromosomes is affected by the number of cell cycles in the folate antagonist system. In this study the lymphocytes were incubated for 96 h in a medium 199 without calf serum, and tri- or multiradial configurations were observed in 6 of 12 cases of fra(X) chromosome. The frequency ranged from 0.6% to 7.4% of fra(X) chromosomes. PMID- 3338805 TI - Facts and considerations about sex-specific antigens. PMID- 3338806 TI - Automatic decomposition of selective needle-detected myoelectric signals. PMID- 3338807 TI - A simplified arithmetic detector for EEG sharp transients--preliminary results. PMID- 3338808 TI - Epidermal and endosteal sources of endogenous electricity in injured canine limbs. PMID- 3338809 TI - A noniterative approximate solution method for volume conductor problems based on the finite difference method. PMID- 3338810 TI - Theoretical electric field distributions produced by three types of regional hyperthermia devices in a three-dimensional homogeneous model of man. PMID- 3338811 TI - Experimental characterization of helical coils as hyperthermia applicators. PMID- 3338812 TI - Effective length of the arterial circulation determined in the dog by aid of a model of the systemic input impedance. PMID- 3338813 TI - Comparison of time domain algorithms for estimating aortic characteristic impedance in humans. PMID- 3338814 TI - Simulation of intrafascicular and extraneural nerve stimulation. PMID- 3338815 TI - Biological mimicry of antigenic stimulation: analysis of the in vivo antibody responses induced by monoclonal anti-idiotypic antibodies. AB - In this study, the induction of protective antibodies against a bacterial pathogen in mice was used as a model for idiotype vaccine development. The antibody responses induced in different strains of mice by the hapten phosphorylcholine (PC) coupled to ovalbumin, PC-OVA, were compared with the responses induced by carrier conjugates of two different anti-idiotopic antibodies. One anti-idiotope, 4C11, exhibits the characteristics of an internal image of phosphorylcholine, and therefore is classified as an Ab2 beta; the other, F6, does not mimic antigen, and therefore is classified as an Ab2 alpha. The analysis of the temporal kinetics of the IgM and IgG1 anti-PC responses induced by nominal and idiotope antigens revealed dynamic responses characterized by changes in the quality and quantity of the antibody populations during the course of the immune response. All three antigens could stimulate antibodies that were PC-specific and T15 idiotope-positive in BALB/c and A/St mice. The highest titre of T15+ anti-PC antibodies was achieved with an immunization protocol which involved priming with Ab2 alpha followed by challenge with PC-OVA. Antibodies specific for the extended hapten, diazophenylphosphorylcholine, and hapten carrier bridge determinants were being stimulated late in the responses to PC OVA. BALB-c, A/St and CBA/N (Xid) mice all produced, late in the response to Ab2 alpha, high T15+ antibody titres which do not bind PC. The induction of T15+, non PC binding, antibody suggests that T15 is a regulatory idiotope, expressed on antibodies having differing antigenic specificities. With regard to vaccine development, these results support the contention that effective induction of antibodies does not depend on stimulating a unique idiotope but can be achieved by anti-idiotypes reacting with different idiotopes. In addition, these results suggest that the combined use of idiotope and nominal antigens in an immunization protocol may provide the maximal protective immunity. PMID- 3338818 TI - Platelet response to aggregated C-reactive protein: fibrinogen-dependent and independent signals. AB - Fibrinogen augmented gel-filtered platelet (GFP) aggregation only during an intermediate level of platelet activation stimulated by aggregated C-reactive protein (CRP) (AggCRP), implying that a mechanism to utilize fibrinogen is not operative or does not require an exogenous source of fibrinogen at near-maximal or threshold levels of platelet activation. By contrast, inclusion of the tetrapeptide fibrinogen antagonist, Arg-Gly-Asp-Ser(RGDS), inhibited both intermediate and near-maximal, but not threshold, levels of platelet activation stimulated by AggCRP. These data suggest that AggCRP initially stimulates platelets independent of fibrinogen but, in so doing, activates a fibrinogen dependent mechanism(s) capable of augmenting the overall extent of platelet stimulation. PMID- 3338816 TI - Isolation and functional characterization of chicken intestinal intra-epithelial lymphocytes showing natural killer cell activity against tumour target cells. AB - Intestinal intra-epithelial lymphocytes (IEL) of SC or FP chickens were isolated and examined for their natural killer (NK)-cell activity against chicken tumour cell lines, LSCC-RP9 (RP9), LSCC-RP12 (RP12), MDCC-MSB-1 (MSB-1) and MDCC-CU36 (CU36). In general, IEL of satisfactory yield and of good viability were obtained with EDTA treatment of the gut tissues, followed by rapid passages of the resultant cells through nylon-wool columns and centrifugation on two-step Percoll density gradients (45% and 80%). In 4-hr and 16-hr 51Cr-release assays, the NK cell activity of chicken IEL depended not only upon the type of target cells but also upon the incubation time and the host genetic background. RP9, MSB-1 and CU36 were susceptible to NK lysis by IEL and by spleen cells, while RP12 was resistant to lysis even after a prolonged incubation. In kinetic studies the cytotoxicity was detactable from 2 hr after incubation and progressively increased up to 16 or 18 hr. The IEL of SC chickens revealed significantly higher levels of NK-cell activity against RP9 than FP-strain chickens, whereas their splenic NK-cell activity was not significantly different. Against MSB-1 targets, however, IEL of SC and FP chickens showed similar levels of NK-cell activity while their spleens did not (being higher in FP). When tested in FP chickens, IEL NK-cell activity was inhibited by the addition of unlabelled homologous target cells. In general, NK-cell activity was higher in the jejunum and ileum than in the duodenum and caecum. Efforts to enrich IEL NK-effector cells by discontinuous Percoll gradients were not successful. The results of the present study show that IEL of chicken intestine contain effector cells that can mediate NK-cell activity against chicken tumour cells. PMID- 3338817 TI - Rate of incorporation of radiolabelled nucleosides does not necessarily reflect the metabolic state of cells in culture: effects of latent mycoplasma contamination. AB - In response to cell-free conditioned medium derived from the human bladder carcinoma line T24 (T24 SN), we found greatly reduced incorporation of tritiated thymidine and uridine ([3H]TdR, [3H]UR) by the human carcinoma lines UCHNCu (small-cell lung carcinoma) and LS174T (colon carcinoma). The effect was not due to an excess of nucleosides or cytokines known to be present in T24 SN. Cell cycle distribution, increase in cell numbers, and de novo nucleoside synthesis in the indicator cells were only slightly altered. This was in contrast to the gross reduction in [3H]TdR/[3H]UR incorporation and seemed to indicate selective downregulation of pyrimidine-salvage pathways, despite ongoing polynucleotide synthesis. Spontaneous [3H]TdR uptake remained low for several passages in vitro but was readily restored by pharmacological inhibition of de novo pathways with 5 fluoro-deoxy-uridine (5-FUdR). This suggested a stable but reversible regulatory effect of T24 SN on the pyrimidine metabolism of the indicator cells. Further investigation showed degradation of [3H]TdR by a particle-bound activity in T24 SN. Mycoplasma contamination of T24 had not been detectable using standard cultural and staining methods, but became apparent when T24-cell lysates were hybridized with a recently described DNA probe (Goebel & Stanbridge, 1984). We conclude that latent mycoplasma contamination can stimulate changes in cellular pyrimidine metabolism. Our results provide an example for latent mycoplasma infection mimicking metabolic changes in cultured cells by direct interference of a microbial enzyme with the assay system. We describe a rapid and simple bioassay to detect and distinguish particle-associated and soluble phosphorylase activity by [3H]TdR degradation. It may be a useful screening assay for mycoplasma contamination in tissue culture. PMID- 3338819 TI - Specificity of natural serum antibodies present in phylogenetically distinct fish species. AB - The following fish orders, at different stages of phylogenetic development, were tested for serum antibody activity against actin, myosin, tubulin, thyroglobulin, haemocyanin, single-stranded DNA and trinitrophenyl (TNP): Elasmobranches (sharks), Chondrosteans (sturgeons), and Teleosts (bony fish). Significant antibody activity was found against all these self and non-self antigens but, in particular, high titres of natural anti-TNP antibodies were noted. Anti-TNP antibodies were then isolated by affinity chromatography from pooled sera of several representative fish species, and studied by a non-competitive and a competitive enzyme immunoassay. When the isolated antibodies were tested by the non-competitive assay, Teleost (tench) anti-TNP antibodies bound almost exclusively to TNP, whereas Chondrostean and Elasmobranche antibodies bound mainly to TNP but also to one or more other antigens. When the isolated antibodies were examined by the competitive assay, they could be separated into three groups: (i) anti-TNP antibodies whose binding could be inhibited by TNP only (Teleosts); (ii) anti-TNP antibodies mainly inhibited by TNP but also significantly inhibited by two or three other antigens (Chondrosteans); and (iii) anti-TNP antibodies binding to different antigens but only slightly inhibited by them (Elasmobranches). These antibodies were found by immunocytochemical staining to bind to normal cell constituents, and especially to cytoskeletal proteins. The results strongly suggest that natural antibodies against the seven antigens examined are present in normal fish serum, and that their specificities differ with the stage of phylogenetic development. PMID- 3338821 TI - Defective function of the mononuclear phagocytic system in rats with chronic nephritis. Evidence of a decreased degradation of IgG aggregates by Kupffer cells. AB - In a model of chronic nephritis induced by daily injections of ovalbumin (OVA), the fate of stable, well-defined heat-aggregated rat IgG (A-IgG) was examined by comparing it to that observed in normal rats of the same age. Following i.v. injection of traced amounts of 125I-A-IgG 0.5 hr after the administration of OVA (Group I), rats with nephritis showed delayed blood clearance (t1/2 = 4.6 +/- 2.3 min) compared to the control group (t1/2 = 2.4 +/- 0.8 min). At this time, the following data were also obtained from rats with nephritis: (i) sections of liver, examined by immunofluorescence, showed rat IgG in Kupffer cells reflecting the presence of immune complexes (IC), as was demonstrated in blood by the Raji cell assay; and (ii) rosette formation of IgG-sensitized Affigel 701 beads with Kupffer cells demonstrated decreased Fc receptor-ligand binding in comparison to those of control rats (percentage rosettes: 18.3 +/- 7.2 versus 40.9 +/- 7.9; P less than 0.01). To assess the dynamics of the mononuclear phagocytic system (MPS) in the uptake of immune complexes, in another set of experiments the A-IgG was administered 18 hr after the injection of OVA (Group II). Although a delayed blood clearance of A-IgG was also observed (t1/2 = 4.1 +/- 1.2 min) there were neither circulating IgG-immune complexes nor IgG deposits in the liver, and the percentage of rosette-forming Kupffer cells was increased (75.6 +/- 7.4%). To explain the apparently discordant results between the t1/2 and percentages of rosette-forming Kupffer cells in Group II, binding assays (at 4 degrees and 37 degrees), endocytosis, and catabolism of labelled A-IgG for Kupffer cells were studied. The binding studies at 4 degrees showed that the number of receptor sites per cell was similar in rats with nephritis (6.5 +/- 3.3 X 10(4] and control rats (7.0 +/- 3.1 X 10(4]. However, in rats with nephritis, the affinity constant Ka was significantly lower (0.86 +/- 0.4/M X 10(8] than in control rats (37.4 +/- 13.9/M X 10(8); P less than 0.01). The endocytosis rates of rats with nephritis were significantly decreased throughout the whole period of study compared to control rats, while the catabolism was only different during the final period of the study. On the whole, these data suggest that rats with induced chronic nephritis present an impairment in the immune clearance of IgG aggregates, probably due to decreased processing by Kupffer cells. PMID- 3338820 TI - Non-lethal complement-membrane attack on human neutrophils: transient cell swelling and metabolic depletion. AB - The metabolic consequences of non-lethal complement-membrane attack in neutrophils have been investigated by the measurement of cellular ATP content and functional parameters, including chemotactic and phagocytic responses and the capacity to secrete reactive oxygen metabolites, in cells before and after attack. Immediately after non-lethal complement attack, cellular ATP content was reduced by more than 75%, although lactate dehydrogenase content was unaltered. Energy-requiring cell functions were similarly depressed. Incubation of cells in nutrient medium rapidly restored cell-energy stores and functions, demonstrating the completeness of recovery. Fluorescence-activated cell-sorter studies demonstrated that cells undergoing non-lethal complement attack underwent a reversible cell swelling, the cell diameter rapidly increasing from an average of 8.5 micron to 12 micron, then gradually shrinking back to a final average diameter of 8.2 micron. The results indicate that although non-lethal complement membrane attack causes both metabolic and physical changes in neutrophils, these effects are transient and full functional recovery occurs. PMID- 3338822 TI - Trace elements in biliary calculi. PMID- 3338823 TI - Immunotherapeutic modification by Tinospora cordifolia of abdominal sepsis induced by caecal ligation in rats. PMID- 3338824 TI - Prognostic value of serum prealbumin determination in acute viral hepatitis. PMID- 3338826 TI - Early gastric cancer--a clinicopathological study. PMID- 3338825 TI - Colonic myoelectrical activity in irritable bowel syndrome before and after treatment. PMID- 3338827 TI - Transendoscopic needle aspiration cytology--technical note. PMID- 3338828 TI - Campylobacter jejuni infection with acute self limiting colitis and polyarthritis. PMID- 3338829 TI - Pigment gallstones. PMID- 3338830 TI - Benign recurrent intrahepatic cholestasis associated with retinitis pigmentosa. PMID- 3338831 TI - Adult Hirschsprung's disease: report of two cases. PMID- 3338832 TI - Trichobezoars. PMID- 3338833 TI - Adenoacanthoma of the transverse colon. PMID- 3338834 TI - Pyogenic hepatic abscesses in a neonate. PMID- 3338837 TI - Purification and partial characterization of canine angiotensinogen. AB - A procedure is described to isolate angiotensinogen (renin substrate) from canine plasma. The isolation procedure resulted in an 800-fold purification with a rate of recovery of approximately 12%. The purified protein has a specific activity of 24 micrograms of angiotensin I/mg protein. The amino terminal amino acid sequence of canine angiotensinogen was found to be identical to that of the horse but to differ from that of human and rat angiotensinogens. Canine angiotensinogen was heterogeneous with respect to molecular weight and isoelectric point. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of pure angiotensinogen revealed two closely spaced bands with apparent molecular weights of 58,000 and 56,000. Chromatofocusing showed four isoforms: Peaks of pure angiotensinogen eluted at pH levels of 4.32, 4.23, 4.15, and 4.04. Isoelectric focusing confirmed the presence of four isoforms. Thus, the purification procedure identified two molecular weight forms and four isoforms of canine angiotensinogen. Isolation of the four isoforms will allow their characterization and the study of their physiological significance. PMID- 3338836 TI - Biological variability in Wistar-Kyoto and spontaneously hypertensive rats. PMID- 3338835 TI - Pigment calculi--structure and composition. PMID- 3338838 TI - Enhanced phospholipase C activity in the vascular wall of spontaneously hypertensive rats. AB - To explore the roles of vascular phospholipase C activity in the development of hypertension, phospholipase C activity was examined in the aortic wall of spontaneously hypertensive rats (SHR). Phospholipase C activity was significantly enhanced (+87%, p less than 0.005) in 14-week-old SHR as compared with normotensive Wistar-Kyoto rats (WKY). The enzymatic activities were positively correlated with the levels of blood pressure in both of the rat strains (r = 0.62, p less than 0.003). Vascular phospholipase C was also significantly activated (+62%; p less than 0.006) in the aortic wall of 4-week-old prehypertensive SHR, as compared with age-matched WKY. In contrast, vascular phospholipase A2 activity was unaffected in the aortic wall of either adult or very young SHR. There was no difference in the cardiac phospholipase C activity between adult SHR and WKY. The vascular phospholipase C of SHR had a lower Michaelis constant (Km) value than that of WKY. Moreover, its pH profile and calcium requirement differed in part from those of WKY. These results indicate that the activation of vascular phospholipase C precedes the development of hypertension and that the enhancement may be induced by both quantitative and qualitative changes in phospholipase C in SHR. PMID- 3338839 TI - Abnormal regulation of adrenal angiotensin II receptors in spontaneously hypertensive rats. AB - The aldosterone response to angiotensin II is blunted in spontaneously hypertensive rats (SHR). To determine whether this blunting is due to a defect in angiotensin II receptors, we assessed angiotensin II binding to intact adrenal glomerulosa cells in SHR and normotensive Wistar-Kyoto rats (WKY) that had been fed high or low sodium diets before sacrifice. In rats on high salt intake, we observed no difference between the two strains in either receptor affinity (Kd = 1.0-1.2 nM) or binding capacity (36,000-38,000 receptors/cell). When sodium restricted, WKY increased receptor content more than fourfold to 167,000 sites/cell. SHR increased receptor number to only 103,000 sites/cell, which was significantly (p less than 0.01) less than the WKY increase. The cause of the abnormal receptor regulation remains unclear. Two known receptor regulators, the plasma angiotensin II level and the state of potassium balance, were similar in the two strains. Our results suggest that the blunted aldosterone response to angiotensin previously reported in SHR is due to abnormal angiotensin receptor up regulation in the adrenal gland in response to sodium restriction. PMID- 3338840 TI - High NaCl diet reduces hypothalamic norepinephrine turnover in hypertensive rats. AB - The current study tested the hypothesis that high NaCl diets elevate blood pressure in NaCl-sensitive spontaneously hypertensive rats (SHR-S) by reducing noradrenergic input to depressor neurons in the anterior hypothalamus. SHR-S were studied at 7 weeks of age, and age-matched salt resistant SHR (SHR-R) and normotensive Wistar-Kyoto rats (WKY) were controls. Rats were fed either high (8%) NaCl or control (1% NaCl) diets for 2 weeks, following which norepinephrine turnover in hypothalamus (anterior, posterior, and ventral regions), brainstem (pons and medulla), and thoracic spinal cord was assessed using the dopamine beta hydroxylase inhibitor 1-cyclohexyl-2-mercapto-imidazole (CHMI). Regional brain catecholamines were measured by high performance liquid chromatography with electrochemical detection following intraperitoneal injection of CHMI or vehicle. Disappearance of norepinephrine following CHMI was used as an index of noradrenergic neuronal activity. The 8% NaCl diet caused a significant elevation in blood pressure in SHR-S but not in SHR-R or WKY. Endogenous norepinephrine levels and turnover were lower in the anterior hypothalamus of SHR-S fed 8% NaCl than in those fed 1% NaCl but were not significantly different in other groups. Endogenous norepinephrine levels and turnover were greater in pons of 8% NaCl- fed SHR-S than in those fed 1% NaCl but were not significantly different in other groups. These observations support the hypothesis that reduced noradrenergic input to depressor neurons in the anterior hypothalamus and increased noradrenergic input to neurons in the pons are related to NaCl sensitivity in the SHR-S. PMID- 3338841 TI - Altered erythrocyte and plasma sodium and potassium in hypertension, a facet of hyperinsulinemia. AB - Red blood cell sodium and potassium, plasma potassium, glucose and insulin responses to oral glucose load, serum urate, and plasma triglycerides were determined in a stratified subsample (n = 89) of a representative population sample (n = 1211), comprising 30 nonobese normotensive subjects with normal glucose tolerance (reference group) and 59 subjects representing each of the seven possible combinations of abnormal glucose tolerance, obesity, and hypertension. Rate of cation imbalance (red blood cell sodium greater than or equal to 7.0 mEq/L, potassium less than 92.5 mEq/L, or plasma potassium greater than or equal to 4.5 mEq/L) was 88.1% in subjects with abnormal tolerance, obesity, or hypertension, as compared with 40.0% in the reference group (p less than 0.001). These subjects were also characterized by significantly greater rates of insulin response: 60- and 120-minute postload levels of 100 mU/L or more (88.1 vs 46.7%), plasma triglycerides of 80 mg/dl or more (89.8 vs 53.3%) and serum uric acid of 5.5 mg/dl or more (61.0 vs 26.7%; p less than 0.001 for all). The rate of cation imbalance was significantly associated with each of these three biochemical correlates: insulin response (p less than 0.01), triglycerides (p less than 0.001), and urate (p less than 0.001). In the total population sample, the rate of untreated hypertension increased from 18% to 35% to 55.3% (p less than 0.001), with an increase in the number of biochemical correlates of cation imbalance in combination with glucose intolerance and obesity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338842 TI - Effects of thyroid function on blood pressure. Recognition of hypothyroid hypertension. AB - Hypothyroidism has been known to be associated, at times, with diastolic hypertension. We have found in 40 thyrotoxic patients that the induction of hypothyroidism by radioiodine therapy significantly increased diastolic blood pressure, raising it above 90 mm Hg in 16 (40%) of the patients. Restoration of euthyroidism with thyroxine administration significantly reduced the systolic and diastolic blood pressures in these patients, with a fall in diastolic pressure below 90 mm Hg in nine of 16 patients. The prevalence of hypothyroidism was determined by measurements of serum thyroxine and thyrotropin concentrations in 688 consecutive hypertensive patients, referred for evaluation and therapy of their hypertension. Hypothyroidism was found in 25 (3.6%) of the patients. Restoration of normal serum thyroxine and thyrotropin levels with thyroid hormone replacement therapy lowered diastolic blood pressure to levels below 90 mm Hg in 32% of these patients who could be followed up after withdrawal of all antihypertensive drug therapy when euthyroidism had been restored (i.e., 1.2% of the 688 patients). It is concluded that diastolic hypertension resulting from hypothyroidism is a relatively common disorder, present in 1.2% of our referred hypertensive patients, that should be sought and treated. PMID- 3338843 TI - Association of lipids with integral membrane surface proteins of Mycoplasma hyorhinis. AB - Triton X-114 (TX-114)-phase fractionation was used to identify and characterize integral membrane surface proteins of the wall-less procaryote Mycoplasma hyorhinis GDL. Phase fractionation of mycoplasmas followed by analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed selective partitioning of approximately 30 [35S]methionine-labeled intrinsic membrane proteins into the TX-114 phase. Similar analysis of [3H]palmitate-labeled cells showed that approximately 20 proteins of this organism were associated with lipid, all of which also efficiently partitioned as integral membrane components into the detergent phase. Immunoblotting and immunoprecipitation of TX-114-phase proteins from 125I-surface-labeled cells with four monoclonal antibodies to distinct surface epitopes of M. hyorhinis identified surface proteins p120, p70, p42, and p23 as intrinsic membrane components. Immunoprecipitation of [3H]palmitate-labeled TX-114-phase proteins further established that surface proteins p120, p70, and p23 (a molecule that mediates complement-dependent mycoplasmacidal monoclonal antibody activity) were among the lipid-associated proteins of this organism. Two of these proteins, p120 and p123, were acidic (pI less than or equal to 4.5), as shown by two-dimensional isoelectric focusing. This study established that M. hyorhinis contains an abundance of integral membrane proteins tightly associated with lipids and that many of these proteins are exposed at the external surface of the single limiting plasma membrane. Monoclonal antibodies are reported that will allow detailed analysis of the structure and processing of lipid-associated mycoplasma proteins. PMID- 3338844 TI - Identification and mapping of the temperature-inducible, plasmid-encoded proteins of Yersinia spp. AB - The structural genes of the outer membrane polypeptides of Yersinia spp. (YOPs) and the V antigen of plasmid pIB1 of Yersinia pseudotuberculosis were recently cloned and mapped (A. Forsberg, I. Bolin, L. Norlander, and H. Wolf-Watz, Microb. Pathogen. 2:123-137, 1987). The corresponding genes were localized on pYV019 and pYV8081 of Yersinia pestis and Yersinia enterocolitica, respectively. No obvious differences were observed on comparison of pIB1 and pYV019, whereas pYV8081 showed intragenic as well as extragenic changes. However, one region of plasmid pYV8081, which coded for the V antigen, YOP3, and YOP4a, was essentially conserved among the three plasmids. Since this region is connected with the Ca2+ region, we suggest that the conserved region of the virulence plasmids of Yersinia spp. be extended to include both of these regions. Low amounts of the YOPs were detected in the membrane fraction at 37 degrees C in the presence of 2.5 mM calcium. Only minor differences were noticed when the individual YOPs of Y. pestis and Y. pseudotuberculosis were compared. Several differences were observed when the YOPs of Y. enterocolitica were included for comparison. All Y. enterocolitica proteins, except YOP1, YOP4b, and the V antigen, exhibited changes in their characteristic molecular sizes. Although these differences were within a range of +/- 2 kilodaltons, the isoelectric point was retained for each protein type. PMID- 3338845 TI - Circumsporozoite protein of the human malaria parasite Plasmodium ovale identified with monoclonal antibodies. AB - Monoclonal antibodies (MAbs) have been produced against Plasmodium ovale sporozoites and used to characterize the circumsporozoite (CS) protein. Six MAbs were produced, and all were species specific. By using Western blot (immunoblot) analysis, three polypeptides were detected: a predominant 51,000-Mr polypeptide and two presumed precursor 57,000- and 67,000-Mr molecules. The presence of a repeating epitope in the CS protein of P. ovale was demonstrated by using one of the MAbs in a single-antibody two-site enzyme immunoassay. Three MAbs recognized epitopes on the surfaces of sporozoites; the presence of at least one other epitope within the CS protein, but not on the surfaces of P. ovale sporozoites, was also demonstrated. PMID- 3338846 TI - Effect of dietary restriction on total and bacterium-specific mucosal secretory immunoglobulin A in bile-diverted intestinal self-filling blind loops. AB - The effect of starvation on the mucosal secretory immunoglobulin A (sIgA) response to bacterial antigens was studied in bile-free rat self-filling blind loops constructed at the end of a Roux-en-Y branch of jejunum. Rats were fed a 50% restricted diet for 1 to 4 weeks after surgery. sIgA was measured in the mucosa and lumen by an enzyme-linked immunosorbent assay. Dietary restriction caused a final rise of luminal sIgA which was less than 50% of that of normally fed controls Luminal bacteria counts were not different in the two groups. The percentage of total sIgA precipitated with intestinal bacteria was not significantly affected by dietary restriction, and there was no change in the specific binding of sIgA to several bacterial species. Nonprecipitated sIgA exhibited a low but significant specific binding to bacteria in both diet restricted and fed rats. Diet restriction therefore reduced the total sIgA response to luminal bacteria, but the specific bacterial binding capacity per microgram of sIgA was not altered. In these short-term experiments diet restricted animals appeared to be capable of secreting sIgA in excess of requirement, since the nonprecipitable luminal fraction contained free sIgA with binding capacity for bacteria. The ability of sIgA to react with specific antigens may therefore be of more significance as an indicator of bacterial susceptibility than the measurement of total sIgA. PMID- 3338847 TI - Effect of nutritional constraints on the biosynthesis of the components of the phosphoenolpyruvate: sugar phosphotransferase system in a fresh isolate of Streptococcus mutans. AB - A procedure for the purification of enzyme I (EI) and the protein HPr, the general components of the phosphoenolpyruvate:sugar phosphotransferase system, from Streptococcus mutans serotype c is presented. The method was also applied successfully to the purification of EI and HPr from Streptococcus salivarius, Streptococcus sobrinus, and Streptococcus sanguis. Using specific antibodies obtained against the proteins purified from S. mutans DR0001, we determined quantitatively by rocket electrophoresis the cellular levels of EI and HPr in a freshly isolated strain of S. mutans grown under various conditions in continuous culture. The activity of a few specific EIIs was also determined by an in vitro phosphorylation test. Results indicated that maximum EII activities for glucose, mannose, and 2-deoxyglucose were obtained under conditions of glucose limitation, at pH 7.0 and low dilution rate (D = 0.057/h). Increasing the amount of glucose or the dilution rate (D = 0.40/h) or decreasing the pH from 7.0 to 5.5 resulted in a 1.4- to 24-fold decrease in these activities. The EII activity for fructose was not influenced by the growth conditions in the same way as the other EIIs. The fructose EII was highest at pH 5.5 and at high dilution rate under conditions of glucose or nitrogen limitation and was always repressed at pH 7.0 and at low dilution rates. The intracellular levels of EI were also dependent on the growth conditions. The highest concentration (0.65 nmol/mg of protein) was observed in cells grown under glucose limitation at pH 7.0 and high dilution rate, and the lowest concentration (0.12 nmol/mg of protein) was found in cells grown under glucose excess at pH 7.0 and high dilution rate. The other general component of the phosphoenolpyruvate:sugar phosphotransferase system, the protein HPr, was not influenced significantly by varying growth conditions. PMID- 3338848 TI - Multigenic control of resistance to Yersinia enterocolitica in inbred strains of mice. AB - By using recombinant inbred mice derived from strains genetically resistant or susceptible to Yersinia enterocolitica, we demonstrated a tentative linkage of resistance with the Es-1 locus on murine chromosome 8. No correlation with resistance and genes associated with immune regulation was evident. In addition, resistance appeared to be multigenic. PMID- 3338849 TI - Ultrastructural localization of IgE in peripheral blood monocytes from atopics. AB - Monocyte-enriched preparations derived from peripheral blood leukocytes of atopics were probed via a cocktail comprising peroxidase-conjugated (Fab1)2 fragments of two monoclonal antibodies against human IgE. Reaction product indicative of intracellular IgE was identified by electron microscopy in both large and small vacuoles, and at high magnification exhibited a characteristic granular deposition pattern consistent with highly concentrated (perhaps insolublized) material. IgE-containing vacuoles were observed with comparable frequency to those containing IgG, despite the greater than 10,000-fold relative excess of the latter in serum suggesting highly selective uptake of IgE by the monocytes. These results are similar to those reported recently for IgA in human milk macrophages. PMID- 3338851 TI - Comparison of aqueous grain dusts, cotton dusts, and mold extracts by crossed immunoelectrophoretic techniques. AB - To evaluate the possibility that an immune response is involved in the pathogenesis of grain dust or cotton dust induced respiratory disease, 1 grain dust extract (A) was compared with 4 similar grain dust extracts, a cotton dust extract, and a mixture of fungal preparations, using crossed immunoelectrophoretic techniques and rabbit anti-A sera. All extracts demonstrated a significant number of shared antigenic determinants. These data suggest that grain and cotton dust may induce disease via a common pathogenic mechanism and putative agent(s). PMID- 3338850 TI - Medium conditioned by spleen cells of Nematospiroides dubius-infected mice does not support development of cultured mast cells. AB - The ability of different conditioned media to support mast cell development from precursors in normal bone marrow was evaluated. Many mast cells developed in bone marrow cultures containing medium conditioned by concanavalin-A-stimulated spleen cells of normal mice, Trichinella spiralis-infected mice, or mice infected for 6 days by Nematospiroides dubius. By contrast, medium conditioned by concanavalin-A stimulated spleen cells of mice having 18-day infections of the nematode N. dubius failed to support mast cell development. The difference between medium conditioned by spleen cells of mice having 6-day versus 18-day infections of N. dubius may be due to the life cycle stage of the parasite, larval or adult, present at those times. These results from cultures are consistent with those from in vivo studies in which mice given primary infections of N. dubius failed to develop the intestinal mastocytosis characteristic of nematode infections. PMID- 3338852 TI - Nonresident macrophages are absent from glomeruli in IgA nephropathy. AB - The presence of nonresident cells of monocyte-macrophage lineage was investigated in 50 renal biopsies, including 20 from patients suffering from IgA nephropathy. Histochemical and immunological techniques were used to identify, respectively, nonspecific esterase and peroxidase activities and HLA class II molecules. Although intraglomerular phagocytes were observed in all control biopsies, small numbers were seen in only two samples from patients with IgA nephropathy. This feature is consistent with an impaired clearance of immune complexes, possibly leading to their deposition in the mesangium. PMID- 3338853 TI - Allergenic cross-reactivity of several strains of Trichinella in mice and rats by the passive cutaneous anaphylaxis technique. AB - The cross-reactivity of antiparasite IgE antibody responses induced by allergenic antigens obtained from Trichinella spiralis and Trichinella pseudospiralis was determined by the passive cutaneous anaphylaxis (PCA) technique in BCF1 mice infected with T. spiralis, Trichinella nelsoni, Trichinella nativa, and T. pseudospiralis and in rats infected with T. spiralis and T. pseudospiralis. Our results demonstrate that when the antigen used for the PCA challenge is derived from muscular L1 larvae of T. spiralis, high IgE antibody titres can be detected from sera of animals infected with T. spiralis, T. nelsoni, or T. nativa, but not with T. pseudospiralis, during the entire life cycle of the parasite. However, when homologous antigens are used in the PCA test, we obtained comparable values of IgE titres in rats and mice infected with both T. spiralis and T. pseudospiralis strains. These results suggest the existence of a high degree of immunologic identity between the allergenic antigens of T. spiralis, T. nelsoni, and T. nativa strains, but not T. pseudospiralis. PMID- 3338854 TI - Does 'sugar' permeability reflect macromolecular absorption? A comparison of the gastro-intestinal uptake of lactulose and beta-lactoglobulin in the neonatal guinea pig. AB - Intestinal closure to cow's milk beta-lactoglobulin occurs within 6 days of birth in the guinea pig. Passive intestinal permeability to lactulose persists through the suckling period. The uptake of small water-soluble markers does not reflect macromolecular absorption, and has no place in the measurement of immunologic protein handling by the gut. PMID- 3338856 TI - Demonstration of allergen components in the storage mite Lepidoglyphus destructor by an immunoblotting technique. AB - The allergen composition of crude extracts of the storage mite Lepidoglyphus destructor were investigated by sodium dodecylsulphate polyacrylamide gel electrophoresis and immunoblotting. The allergen components were detected by sera from allergic farmers with a positive radioallergosorbent test to L. destructor. The allergen-antibody complexes were visualized by rabbit anti-IgE and beta galactosidase-labelled sheep antirabbit IgG in a chromogenic substrate. Six out of the forty-three sera also had IgE antibodies to the culture medium, which were neutralized by addition of medium antigens before the demonstration of mite allergen components. A total of 11 allergen components were identified. Two of them were found to be major allergen components, identified by more than 50% of the 43 sera used in the study. These 2 IgE-binding components had molecular weights of approximately 18,000 and 16,000 daltons, respectively. PMID- 3338855 TI - Involvement of PAF-acether in anaphylactic bronchoconstriction induced in guinea pigs by aerosolized antigen. AB - Bronchoconstriction following the aerosolization of PAF-acether or antigen to guinea pigs induces autodesensitization, but the responses to direct spasmogenic substances are not modified. Bronchoconstriction by PAF-acether is not reduced when it is aerosolized to passively sensitized animals previously desensitized by repeated inhalations of the allergen (ovalbumin). In contrast, when passively sensitized animals are initially desensitized to PAF-acether by repeated inhalations of this agonist, ovalbumin aerosolization induces a bronchoconstriction which is significantly reduced when compared with the response obtained in nondesensitized animals though, in this case, the response to aerosolized histamine is not modified. Thus, PAF-acether is released during intrapulmonary anaphylactic shock induced by aerosolized ovalbumin and can be a prime candidate for its development. PMID- 3338857 TI - Immunological suppression of delayed hypersensitivity responses in mouse lungs as reflected by numbers of mononuclear cells, mast cells and mucus-producing cells. AB - The suppression of delayed hypersensitivity (DH) in the lung as reflected by the appearance of mononuclear cells, mast cells and mucus-producing cells was studied in Balb/c mice. Immunosuppression was induced by intravenous and peroral administration of picrylsulfonic acid (PSA) in mice subsequently sensitized with picrylchloride (PiCl). The animals exhibited a decreased DH reactivity as assessed by ear thickness increase compared with mice sensitized but not exposed to PSA pretreatment. In mice exposed to PSA intravenously (suppressed) and sensitized with PiCl there was a decrease in the number of mononuclear cells in the lung after challenge, compared to mice sensitized and challenged only. Similarly, the mast cell and mucus-producing cell numbers were slightly lower in animals immunosuppressed intravenously with PSA compared with sensitized mice. Such a decrease in the numbers of mononuclear cells, mast cells and mucus producing cells in the lung was not seen in animals treated with PSA perorally, although these animals exhibited suppressed DH reaction in the ears. The present results indicate that induction of mononuclear cells and to some extent mast cells and mucus-producing cells in the lung relates to the DH reaction and its regulation. PMID- 3338858 TI - Immunogenicity and allergenicity studies on two beta-lactam structures, a clavam, clavulanic acid, and a carbapenem: structure-activity relationships. AB - Two newer beta-lactam-containing structures, a clavam, clavulanic acid, and a carbapenem, MM22383, have been studied for their intrinsic immunogenicity and allergenicity. Clavulanic acid has a very low immunogenic and allergenic potential, in contrast to MM22383 which is a contact sensitiser in guinea pigs and an immunogen in rabbits. Evidence for the allergenic potential of MM22383 in man through occupational exposure is also presented. Consideration of the chemistry of these two compounds with respect to their reactivity with protein provides a rationale for the marked difference in their behaviour. The importance of stable hapten-protein conjugates and epitope density is discussed in relation to immunogenicity. PMID- 3338859 TI - Detection in allergic individuals of IgE specific for the Australian paralysis tick, Ixodes holocyclus. AB - Three techniques were developed to detect IgE specific to Ixodes holocyclus. The radioimmunoassay (RIA) was found to be superior to both radioallergosorbent test and enzyme immunoassay techniques. Validation of the RIA technique was provided by dilution experiments and by a blind study involving 13 volunteers; the RIA graph was linear over a wide range of concentrations. The RIA ratio clearly discriminated between those volunteers with and without systemic allergic reactions and helped to identify borderline cases showing local or cutaneous allergic reactions. It appears to be suitable for diagnostic and research applications. PMID- 3338860 TI - Carbohydrate-specific human heterophile antibodies in normal human sera that react with xenogeneic cells. AB - Human heterophile antibodies (HHA) that are present in normal human sera (NHS) play an important role in hyperacute xenograft rejection. The aim of this study was to analyze the occurrence, mode of action and molecular specificity of HHA in NHS that are directed against xenogeneic lymphocytes (isolated from mouse, rat, guinea pig, rabbit, cattle and pig) and isolated rat pancreatic islets. All sera contained variable amounts of HHA that killed the target cells via the classical complement pathway. The cytotoxic activity of these HHA was specifically inhibited by certain carbohydrates (alpha-D-melibiose, beta-lactose, beta gentiobiose, beta-cellobiose, D-mannose, N-acetyl-beta-D-mannosamine and alpha-D rhamnose) and by rat IgM. By means of affinity chromatography with immobilized inhibitors we obtained an antibody preparation of mainly IgG type from NHS (up to 3.5 mg/10 ml serum) that reacted strongly with rat lymphocytes and isolated rat pancreatic islets. Though thus far residual xenospecific antibody activity has remained in the sera even after multiple affinity chromatography, these data suggest that specific elimination of HHA is feasible and that it may be thus possible to overcome a major obstacle to xenotransplantation. PMID- 3338861 TI - Induction of secondary IgE antibody response in rats immunized with X-irradiated metacercariae of Paragonimus ohirai. AB - Rats reinfected with Paragonimus ohirai (P.o.) elicited little secondary IgE response to adult P.o. antigen. In contrast, rats immunized with X-irradiated (2 10 krad) metacercariae elicited not only a marked primary IgE response comparable to that in normally infected rats, but also a marked secondary IgE response after challenge infection. Rats immunized with 2 krad X-irradiated metacercariae yielded a higher secondary IgE response than with 5 or 10 krad irradiated ones, and elicited a secondary response lasting at least 1 year. An IgE response to antigen of newly excysted juvenile parasites (NEJ) was clearly different from the IgE response to adult P.o. antigen. The former IgE response was weak after infection or immunization, but after challenge infection a marked secondary response occurred at a level similar to the IgE response to adult P.o. antigen. The secondary IgE responses to adult P.o. and NEJ antigens were also elicited by reinoculation with X-irradiated metacercariae. Cross-absorption experiments confirmed that there were adult type and NEJ type allergens. PMID- 3338862 TI - Heteroclitic antibodies: differences in fine specificities between monoclonal antibodies directed against dinitrophenyl and trinitrophenyl haptens. AB - The inhibition of binding of monoclonal antibodies by different haptens was studied using the 50% antibody binding assay. The binding of antidinitrophenyl and antitrinitrophenyl antibodies to dinitrophenylated or trinitrophenylated bovine serum albumin could be inhibited by monovalent dinitrophenyl or trinitrophenyl epsilon-aminocaproic acid. Some of the antibodies could be inhibited to a greater degree with the cross-reacting haptens than with the haptens homologous to the immunizing antigen, therefore these antibodies were heteroclitic. PMID- 3338863 TI - The distaff and the staff: stereotypes and archetypes of the older woman in representative modern literature. AB - Belles-lettres, dealing with what it means to be human, serve to expose stereotypes, strip them away, and reveal the truth behind the misconceptions, often in terms of archetypes. An all-too-common subject of stereotyping is the aging of women. Much modern fiction and poetry cogently exposes such demeaning stereotypes. References to twenty-five representative poems and nine works of fiction by thirty-five modern authors (American, British, Australian, French) demonstrate that the elderly woman often survives with dignity, even nobility, in a society often insensitive to her plight, that she often ages with grace, retaining her independence, fortitude, and passion for life. PMID- 3338864 TI - Participation in a dual economy and adjustment to retirement. AB - Past studies of adjustment to retirement have generally accepted social structure as a given, and have instead focused upon individual level variables. Based upon criticisms of the white-collar/blue-collar depiction of the work world, an alternative model of the economic system is introduced in an attempt to interject variability in the area of social structure. Utilizing a national sample of men derived from the National Opinion Research Center (1972-1977 inclusive), this dual economic model is employed to assess the effects of sectorial placement of workers on subsequent retirement satisfaction. Findings from multiple regression analysis suggest that such placement renders two qualitatively different groups of retirees, one which is primarily concerned with health, and one for which financial adequacy is more important for retirement adjustment. Overall, it was concluded that structural components must be included in research on the retirement process. In addition, the variability among the different scales used to indicate adjustment to retirement suggests that these may have to be altered to adequately reflect the process of adjustment for each of the groups of retirees. These changes must be based on the structural aspects of the economic order which mandate very different work experiences. PMID- 3338865 TI - Older people in disaster: a comparison of black and white victims. AB - This research examines differential vulnerability to environmental stressors among white and black elderly and non-elderly disaster victims. The research identifies the determinants of psychosocial recovery for those four demographic groups. A total of 431 families who were victims of a tornado were interviewed for the study. A path model of the determinants of psychosocial recovery is presented, and observations are made regarding intervention strategies for older disaster victims. PMID- 3338867 TI - Testing nursing home iatrogenesis. AB - Many nursing home residents, admitted for "temporary" stays, are expected to return to the community. To test the notion of iatrogenesis, this research examined the discharge status of "temporary" residents discharged from a proprietary nursing home during the first six years of its operation. The research noted 1) the extent to which those residents did not return home and 2) reasons for their derailment. The results of the research did not support the notion of iatrogenesis. Of 419 residents, seventy-nine were expected to return to the community. Only 16 percent of those seventy-nine did not. Content analysis of histories, moreover, showed that two chose to remain, four had families who declined to fill caregiver roles, and two quickly deteriorated. Even the histories of the five who generally lost the ability to function independently did not suggest institutional life was to blame. PMID- 3338866 TI - Life-span differences in life satisfaction, self-concept, and locus of control. AB - The literature on age differences in life satisfaction, self-concept, and locus of control reveals a variety of conflicting findings. Nehrke et al. reported a study of elderly institutionalized males that attempted to control for some of the possible sources of variability. The present study extended this effort to a noninstitutionalized life-span sample of males and females in six age groups (fourteen to ninety-four). The age main effect was significant for the locus of control measure. For self-concept, the age and sex main effects were significant. For life satisfaction, the age and sex main effects and their interaction were significant. Generally, lower levels of self-concept and life satisfaction and a more external orientation characterized adolescents and young adults while, with notable exceptions, the remaining age samples were more positive in self-concept and life satisfaction and were more internally controlled. Although the three dependent measures were significantly correlated for the total sample, the correlations involving locus of control were only moderate. The data suggest that at least the life satisfaction and self-concept measures may be viable tools to assess the psychological quality of one's life, and that reliable age differences in well-being can be demonstrated if moderating variables are controlled experimentally or statistically. PMID- 3338868 TI - Successful operant conditioning procedures with an institutionalized aggressive geriatric patient. AB - The present investigation utilized a modified differential reinforcement of other behaviors (DRO) schedule with an exclusionary time-out procedure to treat a sixty nine year-old aggressive male. Dependent measures included confirmed incidents of physical and verbal aggressive behavior monitored across an ABAB design with a four month follow-up. During the experimental conditions, contingent tangible reinforcers were provided for non-aggressive behavior. Such rewards were progressively diminished over the course of treatment utilizing a systematic fading scheme. Results indicated a clear demonstration of behavioral control and clinically significant treatment effects during both experimental periods. Implications for future research are discussed. PMID- 3338869 TI - Formation of DNA adducts and water-soluble metabolites of benzo[a]pyrene in human monocytes is genetically controlled. AB - Formation of DNA adducts and of water-soluble metabolites was studied in monocytes of 86 first-degree relatives of 15 families. Tests were performed with blood monocytes using (G-3H)-benzo[a]pyrene as a model pro-carcinogen. Variance analysis revealed significantly higher inter-familial than intra-familial variations. From these data we conclude that the formation of DNA adducts is genetically controlled. Therefore the enhanced formation of benzo[a]pyrene DNA adducts in lung cancer patients found in earlier studies may reflect a genetic predisposition for lung cancer in some patients. PMID- 3338871 TI - Refining the prognostic significance of DNA ploidy status in colorectal cancer: a prospective flow cytometric study. AB - A consecutive series of 123 colorectal cancers, prospectively followed for 3 years, was studied to determine if the prognostic significance of DNA ploidy related to: (a) thresholds used to define DNA aneuploidy, or (b) aneuploid sub groups defined by DNA index (DI) and peak size. Aneuploidy was defined using 3 methods depending on the minimum proportion of nuclei considered to constitute an aneuploid peak; type 1, 5%; type 2, 10%; type 3, 10% if DI is 1.1-1.8, but 15% if DI is 1.9-2.1. DNA aneuploidy rates were type 1, 75%; type 2, 67%; type 3, 58%. The significance of clinical and pathological correlations varied with the use of different methods. All were associated with a significant DNA diploid survival advantage which was strongest for type 3 (p = 0.006). DI was unrelated to survival irrespective of the presence or absence of an associated S/G2; 33% with a DI of 1.1-1.8 and 35% with a DI of 1.9-2.1 survived. Prognosis was inversely proportional to aneuploid peak size, 48% with small peaks (less than 20%), 30% with intermediate peaks (greater than 20% less than 40%), but none with large peaks (greater than 40%) survived (p = 0.03). We conclude that: (a) thresholds used to define DNA aneuploidy affect the prognostic significance of DNA ploidy; (b) survival is independent of the DI of aneuploid peaks; and (c) measurement of aneuploid peak size refines the prognostic value of DNA ploidy. PMID- 3338870 TI - Estimates of the worldwide frequency of sixteen major cancers in 1980. AB - The numbers of new cancer cases in 16 common sites occurring in 1980 have been estimated for 24 areas of the world for which the United Nations produces population estimates. For the world as a whole, the total number of new cases was 6.35 million, almost exactly evenly divided between the developed and developing countries. In males, the most important sites were lung, stomach, colon/rectum, mouth/pharynx, prostate and oesophagus, and in females breast, cervix, colon/rectum, stomach, corpus uteri and lung. When the two sexes are combined, stomach cancer emerges as the most common cancer in 1980 (669,400 new cases per year), but this estimate is only slightly greater than that of lung cancer (660,500 new cases), and comparisons with earlier estimates for 1975 suggest that, with declining incidence rates for stomach cancer and the continuing rise for lung cancer, the latter would become the most common cancer in the world by the end of 1981. The implications for cancer control in the developed and developing countries of the world are discussed. PMID- 3338872 TI - Macrophages associated with murine tumours express plasminogen activator activity. AB - The fibrinolytic activity of cancer cells has been repeatedly implicated in mechanisms of local spread and tumour invasiveness. Mononuclear phagocytes associated with solid tumours might also contribute to fibrin dissolution at the tumour/host interface through the expression of plasminogen activator (PA) activity. We have investigated the PA activity of tumour-associated macrophages (TAM) from 4 transplanted murine tumours in syngeneic hosts; peritoneal macrophages (native and thioglycolate-elicited) from both tumour-bearing and control animals were studied as reference cells. TAM from 3 tumours (MSV, mFS6, MN/MCAI) had basal levels of PA activity (20% plasminogen-independent) comparable to or higher than those of thioglycolate-elicited peritoneal macrophages from the same tumour-bearing animals. TAM isolated from 1 tumour (MS2) had a PA which was very low (60% plasminogen-independent), but higher than the activity of unstimulated peritoneal macrophages. Molecular analysis of PA by SDS-PAGE electrophoresis and fibrin autography revealed in all macrophages a single species having an apparent MW of 48 kDA. It thus appears that, in some experimental neoplasms, tumour cell vicinity may represent an in vivo stimulus for macrophage PA expression. PMID- 3338873 TI - Recombinant human tumor necrosis factor-alpha: thrombus formation is a cause of anti-tumor activity. AB - In a previous study we showed that recombinant human tumor necrosis factor-alpha (rTNF-alpha) has no cytolytic effect on Meth A fibrosarcoma cells in vitro but that it has a strong anti-tumor activity in vivo. In the present work, we define the in vivo mode of action of rTNF-alpha on solid-form Meth A fibrosarcoma implanted intradermally (i.d.) in mice. rTNF-alpha exhibited strong anti-tumor activity when given intravenously (i.v.) 7 or 10 days after tumor implantation, but not when given 3 days after implantation. Light and electron microscopy showed that rTNF-alpha impaired microcirculation by producing fibrin-like substances in newly formed microcapillaries in 7-day-old tumor tissue. An anti coagulant, dicoumarol, abrogated the effect of rTNF-alpha. Injection of carbon particles showed that the development of capillaries in 7-day-old tumors was more extensive than in 3-day-old tumors, and suggested that the anti-tumor activity of rTNF-alpha depends upon a fully developed fine network of induced capillaries in the tumor. Electron microscopy showed that rTNF-alpha increases the number of primary and secondary lysosomes in the cytoplasm of 7-day-old tumor cells. The results suggest that rTNF-alpha selectively stems the blood flow in newly formed microcapillaries, eventually leading to autolysis of the tumor cells. PMID- 3338875 TI - Housekeeping products: the choice is yours. PMID- 3338874 TI - Biological characterization and oncogene expression in human colorectal carcinoma cell lines. AB - To establish well-characterized cellular reagents for the study of colon carcinoma, we have examined 19 human colorectal carcinoma cell lines with regard to morphology, ultrastructure, expression of tumor-associated antigens, proliferative capacity in vitro, anchorage-independent growth, oncogene expression, tumorigenicity and malignant potential. Cell lines examined were cultured under identical conditions, and in vitro and in vivo analyses were performed in parallel on replicate cultures. Three classes of colorectal cell lines were defined according to their tumorigenicity in nude mice. Class-1 lines formed rapidly progressing tumors in nearly all mice at an inoculum of 10(6) cells. Cell lines belonging to class-2 were less tumorigenic, producing tumors later and at a slower growth rate. Class-3 lines were non-tumorigenic under all experimental conditions tested. By Northern analysis, the oncogenes c-myc, H-ras, K-ras, N-ras, myb, fos and p53 were expressed in nearly all cell lines examined. In contrast, transcripts for abl, src and ros were not detected. The best in vitro predictor of tumorigenicity was colony formation in soft agar. There was no detectable correlation between tumorigenicity and metastatic potential, doubling time in vitro, production of tumor-associated markers, xenograft histology or expression of specific oncogenes. PMID- 3338876 TI - Linking hospital epidemiology and quality assurance: seasoned concepts in a new role. AB - In this initial presentation, certain concepts central to infection control epidemiology have been discussed and related to the evaluation of noninfectious events in medical care. While most of the examples have focused on parallels in noninfectious hazards of hospital care, a more global evaluation of the functional benefit(s) and cost-effectiveness of medical care intervention using similar epidemiologic principles is possible and of equal value. These issues will be discussed in future presentations. It will be our continuing thesis that the current infection control practitioner and hospital epidemiologist will need to become more involved in the quality assurance and risk management activities of their institutions and that training in all fields of medical care evaluation will need to be founded in epidemiology. Programs in quality assurance and risk management must adopt the use of these standard methods and must generate the databases to allow variations from norms in clinical practice to be evaluated. Those in infection control will need to broaden their expertise to include more sophisticated statistical methods, newer strategies in the observational studies of clinical care, the fundamentals of clinical information systems and data handling, and the appropriate national and regional sources of comparative clinical data. Future articles in the Topics series will provide reviews in these areas and serve as a forum for issues in the changing field of hospital epidemiology. The editors welcome comments on the series or manuscripts for review for possible publication. PMID- 3338877 TI - Extraocular myotoxicity of the retrobulbar anesthetic bupivacaine hydrochloride. AB - Morphopathological changes induced in the extraocular muscles by the local anesthetic agent bupivacaine hydrochloride were studied in the monkey using light and electron microscopy. Retrobulbar anesthetic blocks, using 0.75% bupivacaine hydrochloride, were performed in five adult cynomolgus monkeys. Morphological alterations in extraocular muscle fiber types were examined following survival periods of 3-27 days. Bupivacaine injections produced a mild and very limited myopathic response, with changes largely restricted to the global layer singly innervated muscle fiber type which is characterized by low mitochondrial content. For survival times beyond 3 days, this fiber type exhibited peripheral migration and swelling of mitochondria and an outside-in pattern of myofibril dissolution. Some affected fibers also exhibited the Ringbinden or ring fiber pathology. Maximal myotoxic response was observed at 14 days after injections, and pathological changes were largely resolved by 27 days. A more limited analysis of the effects of retrobulbar injection of lidocaine revealed similar morphopathological responses, thereby suggesting that these effects are a property common to the entire class of aminoacyl anesthetics. In contrast to previous observations in other skeletal musculature, the extraocular muscles proved to be unexpectedly resistant to local anesthetic treatment as only limited alterations were observed. The observed muscle fiber type specificity was interpreted to result from differences in the relative ability of muscle fiber types to adapt to anesthetic-induced elevations of intracellular free calcium levels. PMID- 3338878 TI - Effect of long-term contact lens wear on corneal endothelial cell morphology and function. AB - Anterior segment fluorophotometry (topical) and central endothelial cell photography were performed on 40 long-term (2-23 years) contact lens wearers (four groups of ten each: hard, soft, gas permeable, and gas permeable plus prior lens usage) and 40 non-contact lens wearers of similar ages. Morphologically, the endothelial cells of contact lens wearers showed greater variability in size and shape compared to controls. The mean endothelial cell size in contact lens wearers (307 +/- 35 micron2) was smaller than that of controls (329 +/- 38 micron2, P less than 0.01). There was an increase in the coefficient of variation of cell size of the contact lens group (0.35 +/- 0.06 versus 0.25 +/- 0.04 for controls, P less than 0.0001). The endothelial cell mosaic contained a smaller percentage of hexagonal cells in contact lens wearers (66 +/- 8) compared to controls (71 +/- 7, P less than 0.01). There was a compensatory increase in five sided cells. Functionally, there was no difference in corneal clarity, central corneal thickness or endothelial permeability to fluorescein (3.78 +/- 0.57 X 10( 4) cm/min versus 3.85 +/- 0.55 X 10(-4) cm/min for controls) between the two groups. Aqueous humor flow was increased 7% in contact lens wearers. We found no correlation between oxygen transmissibility, estimated underlying oxygen tension, or duration of wear of the contact lenses and any morphologic or functional variable. We also found no differences between the four groups of contact lens wearers except that the gas permeable lens wearers had more hexagonal and less pentagonal cells. Long-term contact lens wear induces morphologic changes in the corneal endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338879 TI - The effect of sodium hyaluronate on the corneal epithelium. An ultrastructural study. AB - The effect of sodium hyaluronate (NaHa) 1% and 0.1% was studied on 14-day chick embryo corneal epithelium by scanning electron microscopy. It was found that NaHa 1% or 0.1% had no toxic effects on the chick corneal epithelium and the normal architecture of the cells and the morphology of the microvilli was well preserved. A combination of NaHa 0.1% and benzalkonium chloride (BAK) 0.01% reduced the toxic effect of BAK on the surface corneal epithelium. NaHa 0.1% provided a better protection of the corneal epithelium against dryness than hydroxyethylcellulose (HEC) 0.1% or phosphate buffer saline (PBS). PMID- 3338880 TI - Modulation of type III collagen synthesis in bovine corneal endothelial cells. AB - Bovine corneal endothelial cells in culture synthesize predominantly type III collagen, unlike rabbit corneal endothelial cultures which synthesize type IV collagen. In an attempt to document whether this type III collagen synthesis by bovine cells is a tissue culture-specific phenomenon, collagens synthesized by organ culture of bovine Descemet's membrane/corneal endothelium complex were compared with those of subsequent tissue culture cells, up to the eighth passage. The biosynthetically labeled collagens were analyzed on SDS electrophoresis. The soluble fractions of tissues extracted with neutral salt followed by pepsin digestion contained only type I collagen; no other radiolabeled collagens were detected in organ culture. When pepsin treatment was eliminated, type IV collagen was identified in the tissue extract by immunoblot analysis using monoclonal antibody; type III collagen failed to show a positive band by immunoblot analysis. The pepsin-treated medium fraction of the primary culture contained types I, III and V collagen; type IV collagen was identified by either the characteristic electrophoretic mobility or by immunoblot analysis only prior to the proteolysis step. The subsequent subcultures continued to synthesize types I, III and V collagen, but type IV collagen was no longer detectable from the third passage on. No substantial quantitative changes in the expression of individual collagens were observed during subculture. From the primary culture, type I collagen accounted for 30%, type III for 60% and type V for 10%. Enhanced expression of type III collagen was observed in the eighth passage and in primary cultures grown on type I collagen matrix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338881 TI - An ultrastructural study of rabbit ocular surface transdifferentiation. AB - When debridement of the rabbit cornea is followed by re-epithelialization from the conjunctiva, a process of transdifferentiation of the endothelium occurs. Goblet cells appear peripherally 1 week after healing of the epithelial defect, are widespread at 2 weeks, and disappear centrally at 3 to 4 weeks. Six weeks after closure of the defect, the epithelium has reverted to the customary corneal appearance. The morphology of the regenerating epithelium was studied by light, transmission and scanning electron microscopy. The precursor cells for the goblet cells were identified in stage 1, before PAS-positive cells were present, as pairs of cells with dark cytoplasm and prominent Golgi. Subsequently, goblet cells were present in pairs, indicating that goblet cells are derived from non goblet epithelial cells, and that they do not simply migrate onto the cornea. At the time of transdifferentiation, loss of goblet cells was shown to occur both by desquamation from the surface and by in situ cell death. PMID- 3338882 TI - Immunocytochemical study of intermediate filaments in cultured human trabecular cells. AB - In order to study which classes of intermediate filaments (IF) comprise the IF of human trabecular cells, we undertook immunocytochemical investigations on cultured human trabecular cells using anti-keratin, anti-vimentin, anti-desmin and anti-glial fibrillar acidic protein (GFAP) rabbit sera. Immunostaining with the keratin antibody and the GFAP antibody only produced nonspecific staining. Immunostaining with the vimentin antibody and the desmin antibody produced intracytoplasmic filamentous staining. Pretreatment of the cells with colcemid to induce the perinuclear concentration of IF resulted in the demonstration of a characteristic perinuclear immunofluorescence, confirming the existence of vimentin and desmin. Some cells showed particularly strong positivity to desmin. The desmin antibody used in this study only faintly labeled the IF of cultured human skin fibroblasts, known to contain vimentin but not desmin. These results suggest that the IF of human trabecular cells are composed of vimentin and desmin, and that human trabecular cells possess muscle cell-like functions. PMID- 3338883 TI - An ultrastructural analysis of plasma membrane in the U18666A cataract. AB - Because the cholesterol concentration of lens fiber cell membrane in general and lens intercellular junctions in particular is comparatively high, it is likely that it plays a major role in maintaining these structures. In addition, the high concentration of cholesterol in fiber cell membrane is also likely to influence membrane fluidity. Subcutaneous injections of U18666A (3 beta-(2 diethylaminoethoxy) androst-5-en-17-one HCl) into rats effects: (1) a blockade of sterolgenesis in the lens; (2) a depletion of lens fiber cell membrane cholesterol; and (3) the development of irreversible nuclear cataracts. In the present study we have analyzed the ultrastructure of lens fiber cell membrane in adult rats, these by the freeze-etch technique. Whereas it has been previously demonstrated that intercellular junctions comprise approximately one-third of the intermediate cortical fiber cell membrane in adult rats, these junctions were completely absent between comparable fiber cells taken from opaque regions of the U18666A cataractous lenses. There was also a concomitant increase in the extracellular space between the opaque fiber cells and a substantial redistribution of intramembrane proteins in the exoplasmic and protoplasmic faces of these cells. These findings support a "hypothesis" that inhibition of endogenous lens cholesterol production leads to damage and/or degeneration of lens fiber cell membrane in general and in intercellular junctions in particular, resulting in the production of an irreversible nuclear cataract. PMID- 3338884 TI - Eccentric fixation with macular scotoma. AB - People with macular scotoma tend to read and visually scan more slowly than others with equivalently reduced visual acuity but intact central fields. We measured fixation eye movements and considered the contribution of fixation variability and centripetal eye drift to poor visual performance. These factors might confound efforts to consistently use an optimum retinal locus outside of the macula. We measured monocular horizontal and vertical eye movements using a search coil eyetracker while subjects with naturally occurring central scotomata or control subjects with simulated scotomata eccentrically fixated a single character that was sized to their visual acuity. Motivated subjects with long standing stable maculopathies were chosen to estimate attainable performance limits. During attempts to eccentrically fixate, an ubiquitous foveal pursuit or centripetal drift tendency was not found; rather a pattern of drift was idiosyncratic from subject to subject. This finding was confirmed by an analysis of eye drift of 32 eyes with long-standing bilateral macular scotomata. Moreover, the eye drift speeds (15-200 minarc/sec) were too low to be of functional significance. Drift speeds during eccentric fixation with a visible target were not significantly different than those after the target was extinguished; however, drift speeds were greater than during foveal fixation. This suggests that the fovea has a specialized control of slow eye movements. Fixation variability increased with scotoma size for both simulated and real scotomata, with an abrupt rise when scotomata diameters exceeded 20 degrees C. A significant minority of subjects (39%) adopted two or more distinct preferred retinal loci (PRL) during fixation. Multiple PRL were also more likely if scotoma size exceeded 20 degrees C. Reasonably steady fixation is thus attainable when central scotoma sizes are smaller than approximately 20 degrees C. PMID- 3338885 TI - Oscillopsia, retinal image stabilization and congenital nystagmus. AB - Most individuals with congenital nystagmus (CN) do not complain of oscillopsia (visual inconstancy) even though the amount of retinal image slip varies considerably according to gaze angle and CN waveform. We induced oscillopsia in four subjects with CN by artificially stabilizing images upon the retina under several conditions. Every subject reported oscillopsia during retinal image stabilization, but the condition of stabilization varied from one individual to another. Our results indicate that a variety of mechanisms operate to maintain spatial constancy in congenital nystagmus; some individuals appear to use one mechanism more than another. Possible mechanisms include use of extra-retinal signals, elevated threshold for motion detection and "suppression" of visual input except during foveation periods. PMID- 3338886 TI - Disparity range for binocular summation. AB - Binocular summation of contrast and stereopsis have been linked because they both disappear under certain pathological conditions. The dependence of stereopsis on spatial frequency prompted us to examine how binocular summation varies with both spatial frequency and binocular disparity. We therefore measured binocular summation at different disparities using spatially localized stimuli which were also restricted in their Fourier composition. Contrast thresholds were measured using three interleaved forced-choice staircases for left and right eye monocular stimuli and a binocular stimulus composed of the two monocular stimuli presented simultaneously. At zero disparity binocular thresholds were 1.4 to 1.6 times lower than monocular. As disparity was increased the ratio between the thresholds became smaller, such that at large disparities it was near 1.2, the value expected from probability summation. The range of disparities over which probability summation was exceeded varied with the spatial frequency of the stimulus. At 6.0 cpd the range was 2-3 deg, but at 2.0 cpd or 0.75 cpd the range increased to 4-6 deg. These values closely parallel the range of disparities over which stereoscopic depth sensations occur, but they exceed the limits within which disparate images of an object can be fused into a single percept. The results support the contentions that "neural" summation occurs in the mechanism for stereopsis, that this mechanism uses spatial frequency selective channels, and that this mechanism is separate from the mechanism which mediates fusion. PMID- 3338888 TI - Kainic acid-induced eye enlargement in chickens: differential effects on anterior and posterior segments. AB - Intravitreal injections of kainic acid were used to examine the significance of normal retinal activity for eye growth in chickens, this acid being chosen because of its known, selective neurotoxic effects on cells in the chicken retina. A 6 nmole dose of kainic significantly reduces amacrine cell numbers when used in very young chickens, while higher doses of kainic acid also affect bipolar and horizontal cell numbers. The effects of intravitreal injection of kainic acid on eye growth were assessed 4 weeks after treatment. A 200 nmole dose of kainic acid, used with day-old and 14-day-old chickens, had opposing effects on the anterior and posterior segments of the eye; while growth of the anterior segment was inhibited, the posterior segment was enlarged, predominantly in the equatorial direction. A 20 nmole dose of this acid similarly affected growth in 14-day-old chickens, but in day-old chickens, the anterior segment was also enlarged and the overall eye enlargement had an axial bias. Myopia was the most common refractive error associated with both patterns of development. A 2 nmole dose of kainic acid was without effect on eye growth. Parallels are drawn between these eye enlargement phenomena and those described in chickens whose visual environments have been manipulated. Our results indicate that normal retinal activity is fundamental to normal eye growth in chickens, and furthermore, that growth of the anterior and posterior segments of the chicken eye are independently regulated. PMID- 3338887 TI - A new method for oxygen supply to acute ischemic retina. AB - This paper introduces a new method for supplying oxygen directly to ischemic inner retina, using an oxygen source in the vitreous. Acute retinal vascular occlusion was created in cat eyes by direct pressure on the optic disk and its margins with a glass probe. The satisfactory occlusion of the retinal vessels was documented by direct observation, and functionally by recording the ERG. The vascular occlusion caused a large decrease in the size of the ERG b wave, with no change in the a wave amplitude. The oxygen source was a catheter made of strands of an oxygen-permeable membrane which was inserted into the vitreal cavity. After successful vascular occlusion was documented, 100% gaseous oxygen was perfused through the catheter while recording the ERG. In response to the perfused oxygen the b wave partially recovered. Ventilating the animal with 100% oxygen when the retinal vessels were occluded also caused recovery of the b wave amplitude. Termination of the vitreal oxygen source caused a decrease in b wave amplitude to the level previously observed after the occlusion of the retinal vessels. When the retinal circulation was restored by removal of the glass probe the b wave recovered. The results show that it is possible to supply adequate oxygen to the inner retina via the vitreous to replace the oxygen normally supplied by the retinal circulation. Modification of this method may be useful for the treatment of recent and incomplete retinal vascular occlusion. PMID- 3338889 TI - Videographic quantification of optic disc pallor. AB - Digitized images of the optic disc, acquired videographically (Rodenstock Analyzer) under green (540 nm) and red (640 nm) illumination, were used to quantify optic disc pallor. The pallor density of each pixel was defined as twice the reflectance under green illumination divided by the sum of the reflectance under red and green illumination. Pallor densities can range from 0 (red) to 1 (white); typical median values were 0.25 for vessels, 0.40 for healthy disc rim, and 0.70 for the lamina cribrosa. The variability of pallor measurements using this technique was determined. Two uniform color fields (Farnsworth-Munsell 100 Hue Test color chips 1 and 18) were imaged five times each using a model eye. Significant (P less than 0.0001) drift of mean pallor densities occurred between images of both sets. The optic discs of seven normal eyes and of seven glaucomatous eyes were imaged nine times each. The non-normal frequency distribution of pallor densities for each image was described by trimmed means and a measure of distribution width. Variability was defined as the standard deviation of the measurements divided by the full scale pallor density. The variability of the trimmed means increased with pallor density (r = 0.99, P less than 0.0001). The variability of distribution width was smaller than that of the mean values, and averaged 3.4% in normal and glaucomatous eyes. Videographic reflectometry may provide useful, quantitative measurements of optic disc pallor. PMID- 3338890 TI - Does impaired contrast sensitivity explain the spatial uncertainty of amblyopes? AB - We investigated the possibility that the spatial imprecision of amblyopic eyes can be accounted for by the relative insensitivity to contrast that has been documented for these eyes. Thresholds for the discrimination of spatial misalignment, a measure of spatial uncertainty, were determined for three amblyopes and one normal for targets ranging in contrast from detection threshold to 99%. We found that spatial uncertainty was greater in amblyopic eyes than non amblyopic eyes for targets equally above contrast threshold, and when the targets were presented at threshold contrast to the nonamblyopic eyes and at 99% contrast to the amblyopic eyes. Our results fail to support the possibility that the spatial imprecision of amblyopic eyes can, in general, be attributed to reduced contrast sensitivity. Different neural abnormalities are presumed to limit amblyopes' performance on different spatial tasks. PMID- 3338891 TI - Abnormal acuity development in infantile esotropia. AB - Monocular and binocular grating acuities were measured using a swept spatial frequency visual evoked potential (VEP) technique in a group of fifteen infants with esotropia and alternating fixation. Both monocular and binocular acuity measures fell significantly below the mean for age-matched normals. Infants with esotropia and alternating fixation did not have significant interocular acuity differences. PMID- 3338892 TI - Effects of neuropeptide Y on the isolated rabbit iris dilator muscle. AB - The effects of neuropeptide Y (NPY) were studied on an in vitro preparation of rabbit iris dilator muscle. NPY by itself (10(-11) M to 10(-6) M) had no effect on the resting tension or on the maximal electrically-induced response (MER) of the dilator. Phenylephrine (10(-9) M to 10(-4) M) caused a dose-dependent contraction of the dilator muscle (7.8% to 40.6% of the MER). The addition of NPY 10(-6) M enhanced the phenylephrine-induced muscle contraction (8.8% to 76.8% of the MER) without altering the EC50 value (5 X 10(-6) M) of the phenylephrine dose response curve. These findings support a modulatory role for NPY on the iris dilator muscle. PMID- 3338893 TI - Synthesis of prostaglandin E in rabbit eyes with topically applied epinephrine. AB - Using radioimmunoassay techniques, we measured the amounts of prostaglandin E (PGE) in the aqueous humor and vitreous body of 22 phakic and ten aphakic rabbit eyes. Either epinephrine and placebo, epinephrine and indomethacin, indomethacin and placebo, or placebo and placebo were administered topically for 5 months. Treatment of aphakic eyes was initiated 1 month after intracapsular lens extraction. Topically applied epinephrine apparently induced the synthesis of prostaglandin, manifested by elevated PGE in the aqueous and vitreous. Phakic eyes treated with epinephrine and placebo had mean PGE levels of 407.33 pg/ml in the aqueous and 177.0 pg/ml in the vitreous, whereas control eyes given only placebo had mean levels of 165.83 in aqueous and 59.17 in vitreous. Topically applied indomethacin inhibited epinephrine-induced synthesis of PGE in the aqueous humor, but had no significant effect in the vitreous. PGE levels, higher in placebo-treated aphakic eyes than in phakic ones, were elevated further by epinephrine treatment (from 388.40 to 1851.60 pg/ml in aqueous of aphakic eyes, and from 236.40 to 850.60 pg/ml in vitreous also of aphakic eyes). Our findings relate to the pathogenesis of epinephrine-induced maculopathy and to the mechanism of the ocular hypotensive effect of epinephrine. PMID- 3338894 TI - Effects of intracameral hydrogen peroxide in the rabbit anterior chamber. AB - The effects of intracameral injection of hydrogen peroxide were examined using different techniques in young (4 to 6 weeks of age, approximately equal to 500 g) and adult (3 to 6 months of age, 2.5 to 3.5 kg) rabbits. A response occurred that included changes in intraocular pressure, increased permeability of the iris vasculature, and swelling of the ciliary processes. The initial fall in intraocular pressure was the same in young and adult rabbits and the time to recovery of normal intraocular pressure was statistically the same in young rabbits as in adults. The loss of iris vascular integrity was more pronounced in adult animals, as judged by the appearance of fluorescein in the iris and anterior chamber. Microscopy revealed that the ciliary processes of young rabbits were unaffected by hydrogen peroxide, whereas in adult animals considerable swelling of the ciliary processes occurred. No polymorphonuclear leucocytes were observed in micrographs, ruling out their involvement in the response. The rate of loss of injected hydrogen peroxide from the anterior chamber was significantly longer in adult relative to young animals. Young animals had statistically higher catalase activity (U/mg wet weight) in iris and corneal endothelium than older animals. Differences exist in both the anterior segment response to, and the rate of clearance of, intracameral hydrogen peroxide injection in rabbits of at least two different ages that may reflect the differences found in tissue catalase concentrations. PMID- 3338896 TI - Measure-set computed tomographic analysis of internal architectures of lumbar disc. Clinical and histologic studies. AB - Measure-set computed tomography (MSCT) scan was performed in 30 adult subjects (17 men and 13 women, mean age 42 years) and eight cadavers (five men and three women, mean age 42 years) to establish prospectively a normal CT pattern of the internal architectures of the lumbar disc. Based on the uniformity or nonuniformity of MSCT composition of the nucleus pulposus (NP) and annulus fibrosus (AF), and also on how well NP was discerned from the surrounding AF, the internal architecture could be categorized into well-defined (WD), intermediate (IM), and ill-defined (ID) types. An age and prevalence study of the categorized disc showed that, with age, the disc undergoes an architectural transformation from WD through IM to ID. In addition, 72.5% of WD-type discs and 72.1% of ID type discs occurred in the third and fourth decades and in the sixth and seventh decades, respectively, suggesting that the former is a young form with mild degeneration and the latter an old form with advanced degeneration. Fifty-eight percent of WD-type discs and 60.4% of ID-type discs occurred at L1-3 and L4-S1 levels, respectively, regardless of age. This finding suggests the old form tends to occur at the lumbosacral junction, which is the site of maximum weight bearing in humans. The correlation of water content and histologic findings of degeneration with the three categorized disc types in cadavers showed that WD, IM, and ID discs were associated with the largest, intermediary, and least amount of water of NP, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3338895 TI - In vitro magnetic resonance properties of CNS neoplasms and associated cysts. AB - Fresh surgical specimens of central nervous system (CNS) neoplasms were analyzed with particular attention to differences between the T1 and T2 values of the solid and cystic components. Delineation of solid tumor from cyst is important, particularly when surgical intervention is planned, since only the solid portion need be excised. Total protein concentration determinations and microimmunoelectrophoresis for protein distribution and characterization also were performed on the fluid specimens. To diagnose a lesion on magnetic resonance based on T1 and T2 measurements, one must first have a catalog of values on which to base that diagnosis. The authors are reporting such values at 0.25 T. In addition, protein analysis of the fluid specimens has shown that the cysts of the CNS associated with CNS neoplasms are, in fact, transudates rather than collections of cerebrospinal fluid (CSF). Their T1 should permit differentiation from solid portions of neoplasms and from non-neoplastic syringohydromyelia. PMID- 3338897 TI - An animal model for radiologic biliary interventional procedures. AB - Procedural development, in vivo evaluation, and professional training in interventional biliary radiology require an animal model that provides easy and safe access to the gallbladder and bile ducts. A porcine model was used successfully for catheterization of the biliary system under fluoroscopic control. Permanent access to the gallbladder of ten pigs was achieved with a large-bore cholecystostomy catheter. Catheterization of the common bile duct through the cystic duct was feasible in all animals. Repeated interventional radiologic procedures were performed with intramuscular sedation of the animals, which made this model particularly useful for studies requiring multiple procedures or serial follow-up over several weeks. This article describes the technical aspects of the animal model and the radiographic anatomy of the extrahepatic biliary system in 27 domestic pigs. PMID- 3338898 TI - In vivo analysis of single, pre- and postprocessing quantitative CT techniques. AB - Measurements of bone mineral using single and dual-energy quantitative computed tomography (CT) are examined in vivo in 108 vertebral bodies scanned on a Siemens DRH scanner. Pre and postprocessing dual-energy techniques are compared. In the range of clinically useful kilovoltage, the choice of beam energy does not make a significant difference to the single-energy bone mineral measurement. Postprocessing dual-energy measurement in vivo shows a statistically significant decrease in the amount of mineral measured compared to single-energy measurements, whereas the preprocessing measurement shows a significant increase. PMID- 3338899 TI - The study of perception. PMID- 3338900 TI - Influence of clinical history upon detection of nodules and other lesions. AB - The authors reexamined a suspected difference in the effects of clinical information upon detection of nodules vs. more diverse lesions by directly incorporating classification specificity into detection ROC analysis. Categorical prompts, correct for specific abnormalities, led to detection superior to unprompted reading when non-nodule trials (various lesion types) were analyzed. Trials that contained pulmonary nodules, or contained no lesions but had been preceded by "possible tuberculosis" or "rule out metastatic disease" prompts, failed to demonstrate the diagnostic prompt superiority. Perceptual responses may differ when nodules are compared with more complex lesions. PMID- 3338902 TI - The role of artificial intelligence in medical imaging. PMID- 3338901 TI - The effects of clinical information on film interpretation. Another perspective. PMID- 3338903 TI - Cerebral venous angiomas imaged by MR. PMID- 3338904 TI - Premenstrual syndrome. PMID- 3338905 TI - Fallopian tube implantation for treatment of mullerian anomalies and infertility. PMID- 3338906 TI - Subclavian vascular access through area of resected clavicle. PMID- 3338907 TI - Health care for women. PMID- 3338909 TI - Women physicians--the numbers grow. PMID- 3338908 TI - Radiation protection in Iowa. PMID- 3338910 TI - Osteoporosis--an overview. PMID- 3338911 TI - An electrostatic integrating 222Rn monitor with cellulose nitrate film for environmental monitoring. AB - This paper describes a new type of electrostatic integrating 222Rn monitor designed for the environmental 222Rn monitoring. The window area of the monitor was selected to make the exchange rate optimal. The collecting electrode was positioned on the basis of calculating the internal electric field. A drying agent, P2O5, was placed in the bottom of the monitor, since the collection efficiency of 218Po+ atoms depends on the humidity of the air. The monitors have been calibrated against known 222Rn exposures. The detection limit is 1.2 Bq m-3 for an exposure time of 2 mo. In a small survey, annual mean 222Rn concentrations between 3.7 and 9.5 Bq m-3 in outdoor air and between 6.4 and 11.9 Bq m-3 in indoor air were measured. PMID- 3338912 TI - A specific activity effect in the metabolism of Tc. AB - A study of transfer to milk of three isotopes of Tc indicated different results for 99mTcO4-, 95mTcO4-, and 99TcO4-. When the three isotopes were given orally to lactating goats in separate experiments, the milk transfer coefficients increased with decreasing specific activity. Gut absorption of Tc administered as pertechnetate (TcO4-) was decreased by reduction of TcO4- in the rumen. The rate of reduction of TcO4- in the rumen was greater for higher specific activity doses of Tc. These results suggest that the specific activity of a radioisotope may significantly influence the estimated dose to humans from contaminated milk and, probably, other food products. PMID- 3338913 TI - Transfer coefficients of selected radionuclides to animal products. I. Comparison of milk and meat from dairy cows and goats. AB - The diet-milk transfer coefficient, Fm (Bq L-1 output in milk divided by Bq d-1 intake to the animal) was studied for eight radionuclides that previously had been given little attention. The Fm values for cows and goats, respectively, were: 2.3 X 10(-5) and 1.5 X 10(-4) for 99mTc, 1.4 X 10(-4) and 8.5 X 10(-4) for 95mTc, 1.1 X 10(-2) for 99Tc (goats only); 1.7 X 10(-3) and 9 X 10(-3) for 99Mo; 4.8 X 10(-4) and 4.4 X 10(-3) for 123mTe; 4.8 X 10(-4) and 4.6 X 10(-3) for 133Ba; 5.5 X 10(-7) and 5.5 X 10(-6) for 95Zr; and 4.1 X 10(-7) and 6.4 X 10(-6) for 95Nb. The goat/cow transfer coefficient ratios for milk were approximately 10, but the goat/cow ratios for meat varied by three orders of magnitude. PMID- 3338914 TI - Transfer coefficients of selected radionuclides to animal products. II. Hen eggs and meat. AB - Transfer coefficients to eggs and meat were determined after acute oral doses of 95mTc, 99Mo, 123mTe, 133Ba, 131I, 95Zr and 95Nb to laying hens. The mean values (in units of d kg-1) to eggs and hen meat were, respectively, 3.0 and 0.03 for Tc, 0.87 and 0.18 for Mo, 5.1 and 0.60 for Te, 0.87 and 9.2 X 10(-3) for Ba, 3.2 and 0.01 for I, 2 X 10(-4) and 6 X 10(-5) for Zr, and 1 X 10(-3) and 3 X 10(-4) for Nb. For the same radionuclides administered in the same chemical form, transfer coefficients for eggs are about one to two orders of magnitude higher than for cow's milk, while the transfer coefficients for hen meat are several orders of magnitude higher than for beef. PMID- 3338915 TI - The potential for irradiation of the lens and cataract induction by incorporated alpha-emitting radionuclides. AB - Data on the uptake and retention of Ra and Pu in ocular tissues are reviewed. These data were used to calculate alpha radiation doses to the lens of the eye for patients injected with 224Ra and for individuals exposed to one annual limit on intake (ALI) per year of 224Ra, 226Ra, 228Ra and 239Pu for a period of 50 y. On the basis of this analysis, it is concluded that the induction of lens opacity should not be the factor limiting intake of any radioisotope of Pu or for 224Ra or 226Ra. However, for 228Ra the dose lies within the range of doses received by 224Ra patients who have developed cataracts. PMID- 3338917 TI - Health physics activities in support of the thermal shield removal/disposal and core support barrel repair at the St. Lucie Nuclear Power Plant. AB - The health physics activities related to the removal and disposal of a thermal shield at a nuclear power plant and subsequent repairs to the core support barrel required increased planning relative to a normal refueling/maintenance outage. The repair of the core support barrel was a "first" in the nuclear power industry. Pre-job planning was of great concern because of extremely high radiation levels associated with the irradiated stainless steel thermal shield and core support barrel. ALARA techniques used in the preparation of the thermal shield for removal and shipment to the disposal site are discussed. PMID- 3338916 TI - Partitioning of 238Pu, 239Pu and 241Am in skeleton and liver of U.S. Transuranium Registry autopsy cases. AB - The content of 238Pu, 239Pu and 241Am in the liver and skeleton was estimated from radiochemical analysis of human liver and bone samples obtained at autopsy from former actinide workers whose occupational histories were suggestive of chronic inhalation exposures, with minor skin contamination and wounds documented in a few individuals. For times estimated to be several years to a few decades post intake, 75.8 +/- 15.3% of the total 241Am in the skeleton and liver was found in the skeleton (25 cases) as compared with 63.4 +/- 24.1% for 238Pu (36 cases) and 53.2 +/- 18.2% for 239Pu (43 cases). These differences are significant at the 95% confidence level. Of these cases, 34 included data on both 238Pu and 239Pu and were divided into high and low activity subgroups. The difference in the fractionation of the two Pu isotopes was apparent only in the low activity subgroup, suggesting that the difference observed between the Pu isotopes may be an artifact of the data. The different partitioning of these three nuclides suggests that the ALIs for 238Pu and 241Am may be high by about 25-50% if only the dose to bone is considered and may be high by 12-13%, based on the weighted committed dose equivalent in target organs or tissues. PMID- 3338918 TI - Adequacy of time averaging with diffusion barrier charcoal adsorption collectors for 222Rn measurements in homes. PMID- 3338919 TI - External gamma-ray dose rates from 222Rn progeny indoors. PMID- 3338920 TI - In-vivo measurements of 131I build-up in human thyroids after the Chernobyl reactor accident. PMID- 3338921 TI - 1984 annual radiation doses in Canada: lognormal and hybrid lognormal analysis using maximum likelihood estimation. PMID- 3338922 TI - Reply to lung cancer risk from Rn in Chinese study. PMID- 3338924 TI - IRPA/INIRC reply to Dr. G. C. Miller's comments about radiofrequency electromagnetic field exposure limits. PMID- 3338925 TI - The quality of life of the over 70s in the community. PMID- 3338923 TI - Dissociation between lung cancer and a geological outcrop. PMID- 3338926 TI - The alternative to crisis visiting. PMID- 3338927 TI - School nurses: top of the form. PMID- 3338929 TI - The role of the health visitor with the elderly. PMID- 3338928 TI - Caring for the elderly: taking up the challenge. PMID- 3338930 TI - Ageing well in Riverside. PMID- 3338931 TI - Views on health visiting the elderly. PMID- 3338932 TI - Health visitors talking to mothers. PMID- 3338933 TI - Acute histologic changes in the tracheobronchial tree associated with different suction catheter insertion techniques. AB - Anesthetized, intubated kittens were subjected to one of two procedures: (1) insertion of a suction catheter to a predetermined distance and withdrawal with or without the application of suction or (2) insertion of the catheter until resistance was met and withdrawal with or without the application of suction. There were 5 animals in each group. All 10 of the animals in the "predetermined distance" groups had normal tissues. Of the 10 animals in the "resistance" groups, nine displayed multifocal areas of denuded epithelium and varying degrees of inflammation. One subject from the "resistance/suction" group had normal tissues. One from the "resistance/no suction" group displayed a small hemorrhage into the soft tissue. The Kruskal-Wallis rank test revealed a significant difference (p less than 0.05) between the "predetermined" and the "resistance" groups. The application of suction had no effect on the amount of damage evident. PMID- 3338934 TI - Ethical guidelines. PMID- 3338935 TI - Methods to improve the organ and tissue donation process. PMID- 3338936 TI - Nursing perspectives for the patient receiving ventricular support in the critical care unit. PMID- 3338938 TI - Retention in critical care nursing. PMID- 3338937 TI - Cardiac tamponade resulting from pneumopericardium. PMID- 3338939 TI - Efficacy of a hyperinflation and hyperoxygenation suctioning intervention. AB - Limited data are available on the efficacy of a common endotracheal suctioning intervention to prevent decreases in arterial oxygenation (PaO2) after endotracheal suctioning. We evaluated the effect of five hyperinflation breaths with hyperoxygenation, administered before and after endotracheal tube suctioning, in anesthetized, paralyzed sheep with normal lung function and with abnormal lung function induced by pulmonary acid aspiration. Using a second ventilator to deliver hyperinflation and hyperoxygenation prevented PaO2 from falling below control values after endotracheal tube suctioning in animals with either normal or abnormal lung function. The PaO2 rise after hyperinflation and hyperoxygenation in animals with abnormal lung function, however, was less than that observed in animals with normal lung function. Using manual resuscitation bags to deliver the hyperinflation breaths with hyperoxygenation prevented PaO2 from falling below control values after endotracheal suctioning in animals with normal lung function. When lung function was abnormal, however, there were significant PaO2 decreases when manual resuscitation bags were used to deliver the intervention. These results highlight the difference in PaO2 response when hyperinflation and hyperoxygenation suctioning interventions are delivered with mechanical versus manual techniques. These results also emphasize that the response to hyperinflation and hyperoxygenation differs in subjects with normal versus abnormal lung function. Laboratory evaluation of endotracheal tube suctioning interventions should use abnormal lung function models, rather than normal lung function models, to approximate more closely the critically ill patient population that requires suctioning. PMID- 3338940 TI - Development and testing of an arteriography information intervention for stress reduction. PMID- 3338941 TI - Health promotion in coronary care and step-down units: focus on the family- linking research to practice. AB - Fifteen wives of AMI patients were interviewed to determine the effectiveness of a family assessment tool in helping nurses promote family health in the setting of AMI. The tool was found to be useful, and the study generated information about thoughts, perceptions, and feelings of wives consistent with data from other studies. PMID- 3338942 TI - A description of night sleep patterns in the critical care unit. PMID- 3338944 TI - Congenital heart disease: Dr. Robert Anderson's systematic, sequential analysis of morphologic features. PMID- 3338943 TI - Dynamics of invasive pressure monitoring systems: clinical and laboratory evaluation. AB - Seven pressure monitoring systems were evaluated in the clinical setting and in the laboratory to assess their adequacy for recording invasive blood pressures. We found that a large number of systems used in the clinical setting gave erroneous pressure results because of inadequate dynamic response. Results of testing similar systems in the clinical setting and under optimal laboratory conditions differed greatly. Four major findings were made: (1) Air bubbles in the monitoring systems near the transducer accounted for most of the variability of the dynamic characteristics of systems in the clinical setting; (2) simple catheter transducer system setups performed better, suggesting that simple "kits" be used; (3) membrane domes perform adequately if they are attached with care and according to the manufacturer's specifications; and (4) extension tubing was detrimental to the dynamic response of all systems, especially for pulmonary artery catheters. Fast-flush testing of pressure monitoring systems is needed to ensure the adequacy of dynamic response characteristics in the clinical setting. If the fast-flush characteristics are inadequate, physicians and nurses have the opportunity to troubleshoot the system and remove air bubbles and excessive tubing and to properly attach the transducer domes until optimal characteristics are obtained. PMID- 3338945 TI - Management of seminoma with bulky abdominal disease. AB - Thirty-three cases of seminoma with palpable abdominal disease were treated at the Cancer Control Agency of B.C. between 1948 and 1983. Twenty-three had disease confined to the abdomen (Stage IIB), eight had simultaneous involvement of mediastinal and supraclavicular nodes (Stage IIIB) and two had bone or pulmonary metastases (Stage IV). Five and 10-year disease-specific actuarial survivals for the whole group were 87% and 81%, respectively. Corresponding relapse-free survival was 64%. Of the twenty-three IIB cases, 15 had primary treatment with abdominal radiation only, and eight had prophylactic mediastinal/supraclavicular radiation. Although relapse in IIB was more common in the group receiving abdominal radiation only, survival was unchanged. For the entire IIB group, 5- and 10-year disease-specific actuarial survivals were 91% and 84%, respectively, and corresponding relapse-free survival was 74%. The eight IIIB patients were treated primarily with radiation. Four patients relapsed, all in extranodal sites. Two of these died of disease. Both Stage IV patients required radiation and chemotherapy for long-term disease control. Stage IIB disease can be treated primarily with abdominal radiation, but radiation alone is inadequate when bulky abdominal disease is associated with supradiaphragmatic lymphatic spread or hematogenous metastases. PMID- 3338947 TI - Endocavitary irradiation for rectal cancer and villous adenomas. AB - Endocavitary irradiation has been used for rectal adenocarcinoma and villous adenoma at St. Joseph's Hospital, Milwaukee, Wisconsin since 1978. The 52 patients treated since that time include 32 patients with adenocarcinoma, 19 patients with villous adenoma, and 1 patient with an adenomatous polyp and associated atypia. The average age of these patients (70.5 years) was a full decade older than the average age of all rectal cancer patients. The treatment was administered by a superficial contact machine with most patients receiving 80 Gy over four treatments in a period of 1.5 months. The overall local recurrence rate was 24% in the cancer group and 32% in the villous adenoma group. The 1-, 2 , and 3-year determinate disease-free survival rates were 90.4%, 78.6%, 74.2% and 80.4%; 60.3%, 45.2% for invasive adenocarcinoma and villous adenoma patients, respectively. There was no mortality and very little morbidity associated with the treatment. It is concluded that endocavitary irradiation is an effective alternative to surgery for the treatment of rectal cancer in selected cases. However, villous adenomas do not respond as well. Better results may be obtained for this group of patients by higher doses than were used in this study. PMID- 3338946 TI - Our experience of conservative treatment of anal canal carcinoma combining external irradiation and interstitial implant: 32 cases treated between 1973 and 1982. AB - Between 1973 and 1982, a selected group of 32 patients with anal canal carcinoma received conservative treatment combining external irradiation and 192Iridium implant in a split course. Survival rates at 3 and 5 years are 78 and 61%, respectively. The overall control rate at the primary site is 75%. Tumor response to external irradiation appears to be the major predicting factor of the primary growth control after subsequent interstitial therapy. Two patients (6%) showed severe radionecrosis. The probability to preserve good anal function is 69%. Interstitial irradiation preceded by an external radiotherapy offers a good alternative in the conservative treatment of anal canal carcinoma. PMID- 3338948 TI - Treatment of bladder cancer with interstitial iridium-192 implantation and external beam irradiation. AB - Although interstitial implantation of invasive carcinoma of the bladder has been shown to be an effective treatment in Europe, there has been little experience with this method in the U.S. During the past 6 years, 14 patients at the Hospital of the University of Pennsylvania with single bladder tumors less than 5 cm and no evidence of carcinoma in situ on random bladder biopsies have been treated by a combination of external beam radiation and iridium wire implant. The iridium wire is inserted by an afterloading technique following tumor exposure via suprapubic cystotomy. Following delivery of the prescribed dose, the sources are removed percutaneously. Three patients with recurrent or high grade T1 lesions and 11 patients with T2-T3A lesions have been treated. With a median follow-up of 22 months (range 17 to 65 months), 9 patients are currently NED, 4 patients have died of disease, and 1 patient has died of intercurrent disease. There have been two isolated bladder recurrences, both non-invasive, one having been treated with cystectomy and one being treated locally. In addition, one patient developed regional failure, two developed distant metastases only, and one developed local recurrence following distant failure. The 2-year actuarial local control rate is 84%, with an overall 2-year actuarial survival of 66%. Complications have been minimal. Bladder implantation by this method is technically simple and produces excellent local control with acceptable morbidity. PMID- 3338950 TI - High-dose rate intracavitary therapy for carcinoma of the uterine cervix: II. Risk factors for rectal complication. AB - From August 1978 through December 1982, a total of 267 patients with carcinoma of the uterine cervix were treated using remote afterloading high-dose rate intracavitary therapy (RALS) with non-rigid applicator at our department. The data from 199 previously untreated patients with standard application out of 267 were available for this analysis of rectal complication. The incidence of moderate to severe rectal complication (Kottmeier's grade 2 and 3) was 7% (13/199). Cox's regression model was used for the analysis of risk factors for rectal complication in which even minor injuries (grade 1) were included. By using this method, it was clear that the first significant risk factor was z coordinates of weighted geometric center (WGC-z) (p = 0.0007) and the second corresponding factor was rectal TDF (p = 0.0082), the sum of the rectal dose measured by semiconductor dosimeter (ICD-5) and the dose of external whole pelvic irradiation. From the analysis of application pattern of intracavitary sources, WGC-z indicated the approximation of intracavitary sources to the anterior wall of rectum quantitatively and three-dimensionally. The significance of rectal TDF also implied that the monitoring of rectal dose by ICD-5 had an important role for the prediction and prevention of rectal complication after RALS. PMID- 3338949 TI - Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma. AB - One hundred and sixteen patients with advanced ovarian carcinoma, who underwent primary cytoreductive surgery, received 6-11 courses of chemotherapy by cis platin (50 mg/m2) and adriamycin (50 mg/m2) every 21 days. This was followed by second look laparotomy in 66 patients with no clinical evidence of disease. Consolidation abdominal irradiation was administered to 43 patients. Two techniques of irradiation were employed: between 1980-1983 whole abdominal irradiation was used and patients were to receive 3000 cGy in 4 weeks (Schedule I). Due to myelosuppression only 13 of 26 patients (50%) completed the planned dose of radiation. Between 1983-1985 the target volume was divided into upper and lower parts. First, the lower abdomen received 3000 cGy in 3 weeks, and then the upper abdomen received the same dose (Schedule II). Sixteen of seventeen patients (94%) thus treated, completed the planned dose of radiation. The actuarial survival for all 116 patients was 28% of 5 years. Irradiated patients with negative second look laparotomy had a survival probability of 100% at 24 months. Irradiated patients with microscopic disease at second look operation had an actuarial 5-year survival of 66%. Patients with minimal residual disease at second look laparotomy, receiving consolidation abdominal irradiation, had an actuarial survival of 5% only at 36 months. It is concluded that consolidation radiotherapy is effective in patients with negative or microscopic residual disease at second-look laparotomy. In regard to bone marrow tolerance, split field technique of irradiation is preferred. PMID- 3338951 TI - Assessment of skin dose and its relation to cosmesis in the conservative treatment of early breast cancer. AB - A conservation technique has been developed for the treatment of early breast cancer which involved removal of the tumor, axillary clearance, tumor site implantation with Iridium-192 wires for a boost dose and subsequent treatment of the breast with radical megavoltage external beam therapy. Although the cosmetic results were satisfactory in the majority of the patients, for some it was rated as fair or poor. One variable factor which could have carried some morbidity was the dose of radiation received by the skin. In 51 patients, doses were measured at several points over the treated breast using Thermoluminescent Dosimetry (TLD) at the time of the iridium implant and during the subsequent external beam therapy. Development of skin pigmentation, oedema, and fibrosis were unrelated to the dose received by the skin but the findings suggested that doses greater than 50 Gy to the skin increased the possibility of late (greater than 24 months) telangiectasia over the boosted area. Treatment of tumors in the lower half of the breast, or in large breasts, was associated with a higher incidence of poor cosmesis. This may have been the result of varying posture on the interstitial dose distribution from the Iridium-192 wires and comparison of dose distribution in both supine and erect positions was carried out. PMID- 3338952 TI - From 2 Gy to 1 Gy per fraction: sparing effect in rat spinal cord? AB - Recently published results, from this group, on rat cervical spinal cord, a late responding tissue, indicated no further sparing with lowering the fraction size from 2 to 1.8, 1.5, and 1.3 Gy. In the present experiments a small but probably significant rise in tolerance is suggested, when the dose per fraction was decreased from 2 Gy down to 1 Gy. This rise would however still be much less than what is predicted by the linear quadratic model, based on the experimental data obtained with fraction sizes larger than 2 Gy. PMID- 3338953 TI - Heavy charged-particle induced lesions in rabbit cerebral cortex. AB - Fourteen male rabbits received single doses of 20, 40, and 80 Gy of neon irradiation with an extended Bragg peak. They were sacrificed at 1 day, 1 week, and 6 months post-irradiation. The tissue changes which showed a significant time dose relationship were leakage of carbon particles from blood vessels, focal arachnoiditis, hemorrhage, cystic necrosis, and a total histopathologic score using a point system of grading. The focal nature of the lesions was clearly demonstrated with 2 mm thick macrotome sections. The transition zone between damaged brain and microscopically normal appearing brain was less than 1 mm and the tissue damage induced was morphologically similar to that of other radiation modalities. These findings may have important therapeutic implications for patients. The sharply demarcated boundaries of heavy charged-particle induced lesions suggest these beams will be useful for obliterating tissue in areas where it is critical that a transition from undamaged to severely damaged tissue must occur over a short distance, such as in the central nervous system. PMID- 3338954 TI - Radiotherapy of the rhabdomyosarcoma R1H of the rat: kinetics of cellular inactivation by fractionated irradiation. AB - The kinetics of cellular inactivation by fractionated irradiation in the R1H rhabdomyosarcoma of the rat was studied in the dose range of 1.07 to 12.50 Gy per fraction. Regimens of 1, 3, 5, 7, and 10 fractions per week for several weeks were compared. The number of clonogenic tumor cells per tumor in the course of the different treatment schedules was determined using an in vitro colony assay. The results show that the proliferation of clonogenic tumor cells is decelerated in the course of a fractionated radiotherapy. The deceleration persists for several days after end of treatment, until accelerated repopulation is initiated. The fraction of tumor cells inactivated per week was only dependent on the total dose per week, that is the cellular response was the same whether the weekly dose was applied in 1,3,5,7, or 10 fractions. Thus, the fractionation regimens were considerably more effective than expected from calculations based on single-dose in situ survival curves. PMID- 3338955 TI - Hyperthermia thermometry evaluation: criteria and guidelines. AB - Results of the evaluation of thermometry devices used during hyperthermia treatments at 14 different clinics in the USA are presented. Measurements were made by the Hyperthermia Physics Center (HPC, a national hyperthermia quality assurance program under NCI contract No. N01-CM-37512) according to a protocol. Our sample included thermocouples, fiberoptic thermometers, and high lead resistance thermistors. We found that only some but not all of the thermometers of each kind performed within the +/- 0.2 degrees C acceptability criteria of accuracy. The precision, stability, and response times achieved with each type of thermometer are presented. A summary of perturbations and artifacts typical for each system is presented together with suggested precautions to avoid them during clinical usage. We conclude that although the technology used with each thermometer system is capable of producing a temperature accuracy of 0.2 degrees C, this accuracy is clinically achievable only with a concerted effort and a constant alertness on the part of the investigator. Based on the combined experience of this survey, the clinical investigators we visited, and published reports, we present certain guidelines and procedures that can help to reduce the inaccuracies and improve the reliability of temperature data obtained in clinical hyperthermia trials. PMID- 3338956 TI - Regional hyperthermia--assessment of tolerance to treatment. AB - To assess the patient's tolerance and the complications of treatment associated with delivery of regional hyperthermia using APAS BSD equipment, the data on 30 patients who received regional hyperthermia at the Radiation Oncology Center, Washington University School of Medicine, St. Louis, Missouri, has been reviewed. Most patients presented with advanced or recurrent tumors not amenable to conventional treatment modalities. Hyperthermia was administered in combination with either radiotherapy or chemotherapy. Cardiovascular evaluation was a standard part of pre-treatment work-up. Temperatures were obtained through interstitial probes, catheters inserted into the body cavities and (to record core temperature) esophagus. Local discomfort, anxiety, systemic temperature elevation, and tachycardia were the predominant factors limiting the number of sessions, the duration of sessions and the deposition of power, in 18, 6, 3, and 2 patients, respectively. The complications of treatment were rare. Significant injuries of the superficial tissues were recorded in two patients in whom this could be attributed to contact of urine and stool with the skin surface. Neuropathy was observed in two patients, both of whom had pelvic masses adjacent to or invading into the affected nerves. Both patients had received pelvic irradiation. Neuropathy developed within several days after the first hyperthermia session and proved reversible within several months. No injuries of the visceral organs that could be clearly attributed to hyperthermia have been recorded. PMID- 3338957 TI - Intracatheter hyperthermia and iridium-192 radiotherapy in the treatment of bile duct carcinoma. AB - We report a case of a patient with locally advanced bile duct carcinoma treated with 4500 cGy external beam radiotherapy, followed 3 weeks later by intracatheter 915 MHz microwave hyperthermia and radiotherapy delivered through a biliary U tube placed at the time of surgery. Heating was to 43-45 degrees C for 1 hour followed immediately by intracatheter Iridium-192 seeds to deliver 5000 cGy over a 72 hour period. Prior to treatment, a thermal dosimetry study in phanton was conducted, using the same type of U-tube catheter tubing as in the patient. Orthogonal X rays of the patient's porta hepatis region were used to reconstruct the catheter geometry in the phantom. Proper insertion depth was determined thermographically to obtain maximum heating at the center of the tumor. The maximum SAR was 8.8 watts per kilogram per watt input. During the treatment, the average power applied was 30 W. Six months after therapy, the patient is asymptomatic. Although alkaline phosphatase, SGOT and SGPT have remained elevated, bilirubin has returned to normal and computerized tomographic scans and cholangiograms remain stable. A duodenal ulcer developed after therapy and is healing well with conservative medical management. This case demonstrates that hyperthermia applied through biliary drainage catheters is technically feasible and clinically tolerated. We believe the use of intracatheter hyperthermia in conjunction with external and/or intracatheter radiotherapy in selected patients with unresectable bile duct carcinomas warrants further study. PMID- 3338958 TI - Age factor relevant to the development of radiation pneumonitis in radiotherapy of lung cancer. AB - The significance of age factor for the development of radiation pneumonitis is evaluated in 62 patients with lung cancer between 1977 and 1985. The younger group consists of those less than 70 years old and the elderly group of those 70 years old or more. Radiation doses ranged from 1.5 to 2 Gy, 3 to 5 times per week, therefore the delivered doses were converted to nominal single doses (rets dose). Severe radiation pneumonitis was more often observed in the elderly than in the younger regardless of radiation field size and chemotherapy (n.s.). The onset of radiation pneumonitis occurred earlier in a field size of 90 sq cm or more than in that of less than 90 sq cm in both age groups; there was no significant difference between the two age groups in each field size. The pneumonitis was more frequently noted with increasing rets dose in both age groups (n.s.) regardless of field size and chemotherapy. It is concluded that there is no significant difference in the development of radiation pneumonitis between the younger group and the elderly group, but the pneumonitis is inclined to be more severe in the latter. PMID- 3338959 TI - Dosimetric characteristics of a 6 MV photon beam from a linear accelerator with asymmetric collimator jaws. AB - Dosimetric measurements have been made of a 6 MV photon beam from a linear accelerator equipped with asymmetric jaws. The field size factors for asymmetrically set fields are compared to those for symmetrically set fields. The change of beam quality has been measured as a function of off-axis position of the asymmetric fields to assess its effect on depth dose. Additional measurements include beam penumbra and shape of isodose curves for open and wedge fields as the field opening is moved asymmetrically from the central ray. PMID- 3338960 TI - Seed loss in interstitial radiotherapy of prostatic carcinoma with I-125. AB - Incidence, extent, and time of seed loss after retropubic I-125 implantation was assessed in 52 patients treated for prostatic carcinoma. Radiographic controls up to 62 months were done to evaluate losses. Ninety percent of all patients lost seeds, averaging 8% of total implant number. Loss most frequently occurred within the first month by transurethral routes. Monitoring for seed loss is mandatory to assess dose deficit or inhomogeneous dose distribution, and to avoid environmental radiation hazards. PMID- 3338961 TI - Conservative treatment of breast cancer--where should the booster dose go? PMID- 3338962 TI - Inherent acceleration of tumor dose-rate in hyperfractionated regimens. PMID- 3338963 TI - Is misonidazole induced neurotoxicity permanent. PMID- 3338965 TI - Paranoia and the ego-ideal: death of a salesman's son. AB - Since Freud's (1911) explication of the nature of paranoia, much has been written concerning the dynamic underpinnings of the illness but less have been detailed regarding its manifestations structurally. This essay, with its case illustration, attempts to detail the relationship between paranoia and the ego ideal. Both Blos' (1974) ideas on the negative Oedipus complex and Kohut's (1966) ideas on the developmental line of narcissism prove to be useful ways of linking the clinical picture of paranoia to the psychic structure of the ego-ideal. Both technical aspects of treatment as well as theoretical understandings are explored. PMID- 3338964 TI - Short-term psychotherapy for adolescents: management of initial resistances. PMID- 3338966 TI - The use of successive dreams to facilitate and document change during treatment. PMID- 3338967 TI - Time, reconstruction and psychic reality. AB - This paper illustrates certain relationships between the concepts of time, reconstruction and psychic reality as they appear in the clinical situation. A case example introduces the literature concerning the difficulty of knowing over time "what actually happened." Arlow's model of the two projectors, which has been used to describe psychic reality, is extended from a developmental point of view. Two further case examples then illustrate how attention to the patient's unique psychic reality can lead to different reconstructive problems and interventions. The two case examples raise certain questions about the nature of early experience and the role of external reality. The conclusion takes a broader view of the relationships between time, reconstruction and psychic reality utilizing two examples from contemporary Western literature. PMID- 3338968 TI - The organ culture and grafting of lamprey cartilage and teeth. AB - Cartilage from larval (ammocoetes) and adult (prespawning upstream migrant) lamprey was successfully maintained both when cultured in vitro or grafted in vivo (on the chorioallantoic membrane (CAM) of host chick embryos). In addition teeth from adult lamprey were successfully cultured in vitro. Cartilages were cultured in supplemented Lebovitz's l15 medium at 15 and 20 degrees C for periods of up to 56 d and in supplemented BGJb medium at 37 degrees C for periods of up to 14 d. Cartilages were also grafted onto the CAM for up to 16 d. Both the cultured and grafted cartilages retained their structural and cellular integrity as verified histologically. The viability of the cartilage, even after extended culture periods, was demonstrated ultrastructurally by the presence of chondrocytes displaying abundant rough endoplasmic reticulum, mitochondria, and Golgi apparatii with associated vesicles. In addition the cartilages were shown to be metabolically active in vitro by the incorporation of radioactive sulfur into the matrix. Some cell outgrowth from other tissues, such as connective tissue, muscle, and gill when left adjacent to the cartilage, occurred over time in cultures. No cell outgrowth was observed in CAM-grafted tissue nor was there any invasion of the agnathan tissue by chorioallantoic blood vessels. Teeth cultured in L15-supplemented media for up to 14 d at either 15 or 20 degrees C retained their structural and cellular integrity as observed histologically, with no apparent cell outgrowth. With the successful culture of these tissues, their development, biochemistry, and physiology, potentially of great importance in understanding early vertebrate evolution, can be better understood. PMID- 3338969 TI - Production of rat monoclonal antibody from rat x mouse hybridoma cell lines using microencapsulation technology. AB - The cell growth and monoclonal antibody production characteristics of two rat x mouse heterohybridoma cell lines, designated 187.1 and M1/9.3, were investigated using a biocompatible microencapsulation technology. Both cell lines, derived from the fusion of immunized rat spleen cells with either the NS1 or X63Ag8.653 myeloma cell lines, were found to reach a maximum intracapsular cell density of 1.3 to 1.5 X 10(7) cells/ml during a 27-d culture period. During this period, rat monoclonal antibody accumulated in the intracapsular space of both cultures to a final concentration of 2.0 to 2.8 mg/ml. Comparison of the concentration of rat monoclonal antibody in the extracapsular vs. the intracapsular space of both cultures indicated that significantly less than 1% of the antibody produced by the encapsulated hybridoma cells was capable of transiting the microcapsule membrane during the culture period. Due to the partition of the rat monoclonal antibody within the intracapsular space, the initial purity of the antibody harvested from 21-d microcapsule cultures of 187.1 and M1/9.3 cells was approximately 48 and 75% by weight, respectively. Analysis of the intracapsular protein by sodium dodecyl sulfoxide gel electrophoresis at different times during the culture period demonstrated that the principal contaminant associated with the unpurified antibody was bovine serum albumin. PMID- 3338970 TI - Growth of MTW9/PL2 estrogen-responsive rat mammary tumor cells in hormonally defined serum-free media. AB - Growth of the estrogen-responsive MTW9/PL2 rat mammary tumor cells was demonstrated in serum-free defined medium (designated DDM-1) formulated with F12 DME (1:1 vol/vol) supplemented with 15 mM HEPES pH 7.4, insulin 10 micrograms/ml, transferrin 10 micrograms/ml, sodium selenite 10 ng/ml, triiodo-L-thyronine 0.3 nM, phosphoethanolamine 5 microM, epidermal growth factor (20 ng/ml), 17 beta estradiol 2 nM, and bovine serum albumin 20 micrograms/ml. In DDM-1, the growth rate was about one-half that seen in serum-containing medium. When ethanolamine (50 microM), glutathione (20 micrograms/ml), and linoleic acid/bovine serum albumin (150 micrograms/ml) were added (formulation DDM-2), the growth rate was 80% of serum-containing medium and not seed-density dependent. Deletion of estradiol from DDM-1 or DDM-2 had no effect on growth rate. Also, cells grown in steroid hormone deficient medium for 4 mo. continued to form estrogen-responsive tumors in rats as did cells cultured for the same period in 2 nM estradiol. To investigate autocrine growth factor secretion, a third medium (DDM-3) was prepared by deleting insulin, epidermal growth factor, phosphoethanolamine, estradiol, and both forms of bovine serum albumin from DDM-2. Growth in mitogen free medium equaled 86% of the serum-stimulated rate and was seed-density dependent; phenol red deletion from DDM-3 had no effect on growth rate. Evidence presented suggests that autocrine factors stimulate growth of the MTW9/PL2 cells in DDM-3, and that this secretion may support the growth of estrogen-responsive cells in culture in the absence of steroid hormone. PMID- 3338971 TI - Establishment and characterization of a new human renal cell carcinoma cell line (KRC/Y). AB - A new renal cell carcinoma (RCC) cell line (KRC/Y) has been established from a surgical specimen of a 41-yr-old Japanese female patient with RCC composed of both clear cells and granular cells. This cell line has been maintained for more than 15 mo. through 45 passages with a stable growth. KRC/Y cells have clear or eosinophilic polygonal cytoplasm and round to oval nuclei with one or two nucleoli, and proliferate in a pavementlike cell arrangement with a lack of contact inhibition. By electron microscopy, these cells contain abundant fat droplets and glycogen granules or well-developed organelles or both, which were also observed in the original tumor. The doubling time of these cells at the 15th passage was 73 h. The chromosome number was from 37 to 45 with a hypodiploid modal number of 42. Tumorigenicity was identified by tumor formation after subcutaneous injections of KRC/Y cells in nude mice, which showed close resemblance to the original tumor by light and electron microscope observations. PMID- 3338972 TI - All nod genes of Rhizobium meliloti are involved in alfalfa nodulation by exo mutants. AB - Nodulation of alfalfa by exoB mutants of Rhizobium meliloti occurred without root hair curling or infection thread formation. nod exoB double mutants had the same nodulation deficiency as single nod mutants. Therefore, all the known nod genes are involved in nodule induction by exoB mutants, which apparently occurs via intercellular invasion. PMID- 3338973 TI - Purification and characterization of Clostridium sticklandii D-selenocystine alpha, beta-lyase. AB - We have found a novel enzyme that decomposes D-selenocystine into pyruvate, ammonia, and elemental selenium in extracts of Clostridium sticklandii and C. sporogenes. The enzyme of C. sticklandii has been purified to homogeneity. It has a molecular weight of 74,000 and consists of two subunits identical in molecular weight (35,000). Pyridoxal 5'-phosphate is required as a cofactor. In addition to D-selenocystine, D-cystine, D-lanthionine, meso-lanthionine, and D-cysteine serve as substrates. However, D-selenocysteine, D-serine, DL-selenohomocystine, and L amino acids are inert. The enzyme also catalyzes the beta-replacement reaction between D-selenocystine and a thiol to produce S-substituted D-cysteine. L Selenohomocysteine also can serve as a substituent donor in the beta-replacement reaction to yield selenocystathionine. PMID- 3338974 TI - Acinetobacter cyclohexanone monooxygenase: gene cloning and sequence determination. AB - The gene coding for cyclohexanone monooxygenase from Acinetobacter sp. strain NCIB 9871 was isolated by immunological screening methods. We located and determined the nucleotide sequence of the gene. The structural gene is 1,626 nucleotides long and codes for a polypeptide of 542 amino acids; 389 nucleotides 5' and 108 nucleotides 3' of the coding region are also reported. The complete amino acid sequence of the enzyme was derived by translation of the nucleotide sequence. From a comparison of the amino acid sequence with consensus sequences of nucleotide-binding folds, we identified a potential flavin-binding site at the NH2 terminus of the enzyme (residues 6 to 18) and a potential nicotinamide binding site extending from residue 176 to residue 208 of the protein. An overproduction system for the gene to facilitate genetic manipulations was also constructed by using the tac promoter vector pKK223-3 in Escherichia coli. PMID- 3338975 TI - Rheotactic behavior of a gliding mycoplasma. AB - Mycoplasma mobile, a new gliding mycoplasma isolated from the gills of a fish, was capable of positive rheotaxis; the cells glided upstream in a moving fluid. To our knowledge this is the first demonstration of rheotactic behavior among the procaryotes. PMID- 3338976 TI - Adaptation for growth at various saline concentrations by the archaebacterium Methanosarcina thermophila. AB - We report the ability of Methanosarcina thermophila TM-1 to adapt and grow in media containing NaCl concentrations of 0.005 to 1.2 M. When adapted to marine NaCl concentrations, this species ceased to produce the heteropolysaccharide outer layer typically formed by species of nonmarine origin. concomitant with this adaptation, M. thermophila ceased to grow as multicellular aggregates and existed solely in single-cell form. The sodium ion concentration was critical for the adaptation process, although magnesium ion appeared to contribute to the cell wall stability of single cells. The results suggest that these archaebacteria possess regulatory systems that enable them to adapt to environments with a wide range of saline concentrations. PMID- 3338977 TI - Patterns of plasma imipramine-desipramine concentrations in patients receiving concomitant fluphenazine decanoate. AB - Plasma levels of imipramine and desipramine were monitored in a series of 13 patients with postpsychotic depressions who had a fixed dose of imipramine (150 mg/day) added to their clinically adjusted, stable dose of fluphenazine decanoate. Despite the potential for metabolic inhibition of the tricyclic drug by the neuroleptic drug, no relationship was found between the fluphenazine dose and the subsequent plasma concentrations of imipramine and desipramine. However, plasma antidepressant levels after 1 week at a low dose (50 mg/day) identified patients who later generated high plasma antidepressant levels at the full antidepressant dosage. The clinical implications of these observations are discussed. PMID- 3338979 TI - The development of mania and organic euphoria during ECT. AB - Mania that develops in depressed patients who are undergoing ECT is relatively uncommon and may occur more frequently in bipolar patients. The authors' review of three cases illustrates the importance of the clinician distinguishing mania from organic euphoric states that can also develop during ECT. Severity of cognitive impairment and the presence of silly or inappropriate laughter are useful in making this distinction. Capacity to clinically evaluate the persistence of depressive symptoms should determine whether ECT can continue when an organic euphoric state develops. PMID- 3338980 TI - Lithium tremor and caffeine intake: two cases of drinking less and shaking more. AB - Lithium tremor worsened in two patients when caffeine (coffee) was eliminated from their diets. An associated reduction in renal lithium clearance resulting in increased serum lithium level is thought to be the mechanism. PMID- 3338978 TI - Alprazolam in the treatment of panic attack patients with and without major depression. AB - Sixteen patients with panic attacks were treated with alprazolam at an anxiety clinic between March 1982 and April 1983. For all patients charts were reviewed for baseline data and treatment results at 1 and 6 months. Quantitated self rating scales and the Clinical Global Impressions scale were used to assess progress. Alprazolam appeared effective for panic, agoraphobia, and depressive symptoms in 7 of 11 patients with either panic disorder or agoraphobia with panic attacks (DSM-III-defined diagnoses); side effects occurred in 4 of the 11 patients, were limited to oversedation, and resulted in no discontinuations of drug. However, alprazolam was ineffective in controlling panic, agoraphobia, and depression in 5 patients with panic attacks and secondary major depressive episode; for this group of patients, side effects were apparently paradoxical and required drug discontinuation in 3 of these 5 patients. PMID- 3338982 TI - Nonneuroleptic malignant syndrome. PMID- 3338981 TI - Major depression, anxiety, and substance abuse in a multiple sclerosis patient: diagnosis, treatment, and outcome. PMID- 3338983 TI - Verapamil-carbamazepine neurotoxicity. PMID- 3338984 TI - Isolation and sequence analysis of a complementary DNA encoding rat liver L gulono-gamma-lactone oxidase, a key enzyme for L-ascorbic acid biosynthesis. AB - L-Gulono-gamma-lactone oxidase, one of the microsomal flavin enzymes, catalyzes the last step of L-ascorbic acid biosynthesis in many animals; however, it is missing in scurvy-prone animals such as humans, primates, and guinea pigs. A cDNA clone for this enzyme was isolated by screening a rat liver cDNA expression library in lambda gt11 using antibody directed against the enzyme. The cDNA clone contained 2120 nucleotides and an open reading frame of 1320 nucleotides encoding 440 amino acids of the protein with a molecular weight of 50,605. The amino terminal sequence (residues 1-33) of the enzyme isolated from rat liver completely coincided with the corresponding part of the deduced amino acid sequence. The identity of the cDNA clone was further confirmed by the agreement of the composition of the deduced amino acids with that determined by amino acid analysis of the enzyme. Hydropathy analysis of the deduced amino acid sequence revealed several hydrophobic regions, suggesting that they anchor the protein into the microsomal membrane. The deduced amino acid sequence showed no obvious homology with the flavin-binding regions of other eight flavoenzymes. PMID- 3338985 TI - Refined structure of chicken skeletal muscle troponin C in the two-calcium state at 2-A resolution. AB - The structure of troponin C has been refined at 2A resolution to an R value of 0.172 using a total of 8,100 reflections. Troponin C has an unusual dumbbell shape with only the two C-domain high affinity sites III and IV occupied with metals, while the pair of N-domain low affinity sites I and II are devoid of metals. The coordination of the Ca2+ approaches seven with the last glutamic acid residue in each site forming an asymmetric bidentate ligand. The flanking helices in the metal-bound EF hands are in similar orientation (both 113 degrees) while in the apo sites they are more obtuse (134 and 149 degrees). The EF hands of holo sites III and IV are similar while the apo sites I and II are less similar (rms for backbone atoms, 0.78 and 1.44). The half-loops of the 12-residue holo and apo sites show better agreement than the full loops themselves, suggesting a hinge motion at the midpoint of the loops. The long central helix is stabilized by electrostatic interactions and salt bridges between charged side chains spaced at 3 or 4 residues along the helix. A cluster of water molecules encircle the long helix and hydrogen bond to the backbone carbonyls. At the beginning of the B helix, a water molecule is interposed at each of two consecutive backbone NH...OC hydrogen bonds. The terminal pair of helices A/D (apo) match with E/H (holo), and the internal pair of helices B/C (apo) match with F/G (holo). Thus, muscle contraction may be triggered by Ca2+ binding to loops I and II which results in a concerted rearrangement of residues in the loops, including the essential Gly at position 6 in each loop. This rearrangement than causes a reorientation of helices B and C along with the BC linker. PMID- 3338986 TI - Mechanisms of oxidant-mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation are major intracellular targets inactivated by hydrogen peroxide. AB - Inhibition of ADP phosphorylation by both glycolysis and mitochondria in P388D1 cells exposed to H2O2 is described. Net glucose uptake and lactate production were inhibited by oxidant exposure (ED50 = 50-100 microM). Glycolysis was specifically inactivated at the glyceraldehyde-3-phosphate dehydrogenase step by three independent mechanisms: (a) direct inactivation of the intracellular enzyme (ED50 approximately equal to 100 microM); (b) reduction of the intracellular concentration and redox potential of its nicotinamide cofactors; and (c) a cytosolic pH shift further from the enzyme optima. Consistent with inhibition of glycolysis at the glyceraldehyde-3-phosphate dehydrogenase step, a rise in the intracellular concentration of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-bisphosphate was observed. The calculated combined inhibition of glyceraldehyde-3-phosphate dehydrogenase activity could be reasonably correlated with the depression in glycolytic flux rate with the appropriate modeling. The steady-state contribution by mitochondria to the total intracellular ATP pool was indirectly determined by the use of various metabolic inhibitors and was found to rapidly decline following exposure to 300-800 microM H2O2. The inhibition of ADP phosphorylation appeared to be related more to the direct inhibition of the ATPase-synthase complex rather than to the diminished capacity of the respiratory chain for coupled electron transport. Both the estimated rates of ADP phosphorylation by glycolysis and mitochondria and the estimated rate of ATP hydrolysis by ongoing metabolism were utilized to model the approximate decline in intracellular ATP expected at 15-min exposure to various H2O2 concentrations. Theoretical calculations and the measured intracellular ATP status were in good agreement. Oxidant exposure for 15 min resulted in dose dependent killing of the cells (ED50 = 500 microM), indicating a close correlation between H2O2-mediated loss of intracellular ATP and cell viability. The possible contribution of impaired energy homeostasis during oxidant-mediated injury to the process of cell dysfunction and death is discussed. PMID- 3338988 TI - An epimerase-reductase in L-fucose synthesis. AB - The first committed enzyme in GDP-L-fucose formation from GDP-D-mannose is GDP-D mannose 4,6-dehydratase, which forms GDP-4-keto-6-deoxy-D-mannose. The uncertain enzymatic steps beyond this point were examined in this study. Assays were developed for the epimerase and reductase activities which the putative pathway would predict. A protein was isolated exhibiting homogeneity by several criteria. This single protein, which forms GDP-L-fucose from GDP-4-keto-6-deoxy-D-mannose and NADH, appears to possess both epimerase and reductase capabilities and may be termed GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase. Analysis on a molecular sieve column using fast protein liquid chromatography established a molecular weight of 63,100 for the native enzyme, whereas sodium dodecyl sulfate polyacrylamide gel electrophoresis established a subunit molecular weight of 31,500. PMID- 3338987 TI - Sangivamycin, a nucleoside analogue, is a potent inhibitor of protein kinase C. AB - Protein kinase C functions prominently in cell regulation via its pleiotropic role in signal transduction processes. Certain oncogene products resemble elements involved in transmembrane signaling, elevate cellular sn-1,2 diacylglycerol second messenger levels, and activate protein kinase C. Sangivamycin was unique among the nucleoside compounds tested in its ability to potently inhibit protein kinase C activity. Inhibition was competitive with respect to ATP for both protein kinase C and the catalytic fragment of protein kinase C prepared by trypsin digestion. Sangivamycin was a noncompetitive inhibitor with respect to histone and lipid cofactors (phosphatidylserine and diacylglycerol). Sangivamycin inhibited native protein kinase C and the catalytic fragment identically, with apparent Ki values of 11 and 15 microM, respectively. Sangivamycin was an effective an inhibitor of protein kinase C as H-7, an isoquinolinsulfonamide. Sangivamycin did not inhibit [3H]phorbol-12,13-dibutyrate binding to protein kinase C. Sangivamycin did not exert its action through the lipid binding/regulatory domain; inhibition was not affected by the presence of lipid or detergent. Unlike H-7, sangivamycin selectively inhibited protein kinase C compared to cAMP-dependent protein kinase. The discovery that protein kinase C is inhibited by sangivamycin and other antitumor agents suggests that protein kinase C may be a target for rational design of antitumor compounds. PMID- 3338989 TI - Transient kinetics of heparin-catalyzed protease inactivation by antithrombin III. Linkage of protease-inhibitor-heparin interactions in the reaction with thrombin. AB - Heparin (H) was previously shown to accelerate the inactivation of alpha-thrombin (T) by antithrombin III (AT) primarily by promoting the initial binding of thrombin and AT in a ternary T.AT.H complex intermediate without significantly influencing the subsequent product formation step (Olson, S. T., and Shore, J. D. (1982) J. Biol. Chem. 257, 14891-14895). In the present study, the protein heparin interactions which contribute to the assembly of the ternary complex intermediate and their linkage were quantitated by equilibrium binding and stopped-flow kinetic studies at pH 7.4, I 0.3, 25 degrees C, using p aminobenzamidine (P) as a fluorescence probe. Equilibrium binding studies of the AT.H and T.H binary complex interactions monitored by the 40% enhancement in AT fluorescence or the 16-18% quenching of thrombin-bound p-aminobenzamidine fluorescence, respectively, indicated a 100-fold greater affinity of AT for heparin (KAT,H 0.23 microM) as compared to thrombin for heparin (KT,H 35-42 microM). Consistent with this large difference in affinities, rapid kinetic studies indicated that assembly of the ternary complex occurred predominantly as a bimolecular association between the AT.H binary complex and free thrombin. Thus, under pseudo-first order conditions ([AT]o, [H]o much greater than [T]o much less than [P]o), the observed thrombin inactivation rate constant (kobs) exhibited a saturable dependence on [AT]o or [H]o when [H]o much less than KT,H, reflecting a KAT,H (0.25 microM) similar to that directly determined by equilibrium binding. Moreover, competitive inhibition of the reaction by T.H binary complexes was indicated from the hyperbolic decrease in kobs produced by heparin with either high or low affinity for AT or active-site blocked thrombin at concentrations comparable to KT,H. This behavior was consistent with values of KT,H (27-51 microM) similar to those determined directly from equilibrium binding measurements. Comparison of the affinities of the binary protein-heparin interactions with the affinity of thrombin for AT.H complex in the ternary complex measured previously, indicated that the affinity of either protein for heparin was enhanced about 10-fold by the prior binding of the other protein to heparin. This linkage of the protein-heparin interactions implies that the ternary complex will be assembled at thrombin, AT, and heparin concentrations considerably lower than those predicted from previous reaction models which fail to account for this linkage. PMID- 3338990 TI - Kinetics of activation of the respiratory burst oxidase in a fully soluble system from human neutrophils. AB - In a fully soluble system from resting human neutrophils, activation of the respiratory burst oxidase under defined conditions was found to follow first order kinetics. The manner in which this first-order activation process varied with the concentrations of the individual components in the activating system suggested the following. 1) The respiratory burst oxidase occurs in two forms that can be distinguished by their Km values for NADPH. The low-affinity form contains one component (M) from the membrane and two components (S and C alpha) from the cytosol, while the high-affinity form contains an extra cytosolic component (C beta). 2) The active forms of the oxidase are generated in the following reactions: (formula; see text) where S is a stabilizing component and where M.S is an activated form of M.S that is capable of binding C alpha and C beta to produce the active oxidase species M.S.C alpha (the low-affinity form) and M.S.C alpha C beta (the high-affinity form). 3) SDS activates the oxidase by mediating the conversion of M.S to M.S. PMID- 3338991 TI - The biological importance of each amino acid residue of the troponin I inhibitory sequence 104-115 in the interaction with troponin C and tropomyosin-actin. AB - To systematically evaluate the contribution of each amino acid residue of the troponin I (TnI) inhibitory region (104-115), 14 synthetic analogs were synthesized by the solid-phase method. The analogs consisted of either single glycine or multiglycine replacements. The importance of the substituted amino acid(s) was determined from the extent of inhibition of the acto-S1 ATPase activity and the strength of binding to a troponin C (TnC) high pressure liquid chromatography affinity column of each synthetic analog. Every residue of the TnI sequence (104-115) is necessary to achieve maximum inhibition of the ATPase activity. However, the analogs quantitatively differed in the amount of inhibition induced. The TnI analogs bound less tightly to the TnC affinity column than the native synthetic peptide indicating that all residues in the TnI sequence contribute to the binding of TnC in the presence of Mg2+ or Ca2+. In the presence of Ca2+, there is a definite increase in the strength of the interaction between most analogs and TnC. This is accompanied with a shift toward a more specific interaction with the C terminus of the TnI inhibitory sequence. PMID- 3338992 TI - A thermodynamic study of the interaction between human complement components C3b or C3(H2O) and factor B in solution. AB - The fluid-phase interaction between factor B and an activated form of C3 (C3b or C3(H2O)) is fundamental to the formation of the alternative complement pathway C3 convertase. The present study reports on the thermodynamic parameters that govern these interactions. The extrinsic fluorescent probe 8-anilino-1-naphthalene sulfonate (ANS) and factor B were found to act as competitive ligands in binding to C3b. Thus, complex formation between C3b or C3(H2O) and factor B could be monitored by the quenching of C3b/C3(H2O)-dependent ANS fluorescence upon the addition of B. Under physiological conditions (0.5 mM Mg2+, 37 degrees C, mu = 0.15), the Ka governing the binding of C3b to B was 2.5 X 10(6) M-1, whereas the interaction of C3(H2O) with factor B was of 5-fold lower affinity. Both reactions were endothermic, with the van't Hoff enthalpy being approximately +16.0 kcal mol 1 in each case. Thus, a large positive entropy change provides the net driving force in these interactions. Although Ka increased at higher Mg2+ concentrations, this was not an enthalpy-mediated phenomenon. Taken together, these data are consistent with hydrophobic interactions being dominant in C3b.B or C3(H2O).B complex formation. The enhancement of complex formation by Mg2+ and concomitant increase in delta S suggests that the metal ion plays a role in increasing the number of hydrophobic contacts. PMID- 3338993 TI - Kinetic studies on the role of elongation factors 1 beta and 1 gamma in protein synthesis. AB - An equilibrium isotope exchange technique was used to measure in an Artemia system the catalytic influence of elongation factor (EF) 1 beta gamma on the dissociation of GDP from the complex of elongation factor 1 alpha.[3H] GDP in the presence of an excess of free GDP. The kinetic data demonstrate that, in analogy to procaryotes, dissociation of GDP occurs via the formation of a transient ternary complex of EF-1 alpha.GDP.EF-1 beta gamma. The rate constants for the dissociation of GDP from EF-1 alpha.GDP and from the ternary complex EF-1 alpha.GDP.EF-1 beta gamma were found to be 0.7 x 10(-3) and greater than or equal to 0.7 s-1, respectively. The equilibrium association constants of GDP to EF-1 alpha.EF-1 beta gamma and of EF-1 beta gamma to EF-1 alpha.GDP were found to be 2.3 x 10(5) and 4.2 x 10(5) M-1, respectively. Judged from the known elongation rate in vivo and kinetic constants of nucleotide exchange, it was estimated that the recycling of EF-1 alpha may be a rate-controlling step in eucaryotic translation. As a model for GTP exchange, the formation of the ternary EF-1 alpha.guanylyl (beta gamma-methylene)diphosphonate.EF-1 beta gamma complex was also studied. It was observed that both an increase of the level of aminoacyl tRNA and of temperature favored the dissociation of this complex, thereby enabling EF-1 beta gamma to recycle as a catalyst. This behavior would explain the frequent occurrence of a heavy form of elongation factor 1 in extracts of the eucaryotic cell. PMID- 3338994 TI - Receptor-mediated activation of electropermeabilized neutrophils. Evidence for a Ca2+- and protein kinase C-independent signaling pathway. AB - Electrically permeabilized neutrophils were used to study the mechanism of activation of the respiratory burst by the chemotactic agent formyl-methionyl leucyl-phenylalanine (fMLP). Permeabilization was assessed by flow cytometry, radioisotope trapping, and by the requirement for exogenous NADPH for oxygen consumption. A respiratory burst could be elicited by fMLP, phorbol ester, or diacylglycerol in permeabilized cells suspended in EGTA-buffered medium with 100 nM free Ca2+. The fMLP response persisted even in cells depleted of intracellular Ca2+ stores by pretreatment with ionomycin. Therefore, a change in cytosolic free Ca2+ ([Ca2+]i) is not required for receptor-mediated stimulation of the respiratory burst. The responses induced by phorbol ester and diacylglycerol were largely inhibited by H7, a protein kinase C antagonist. In contrast, the stimulation of oxygen consumption by fMLP was unaffected by H7. These results suggest that a third signaling pathway, distinct from changes in [Ca2+]i and activation of protein kinase C, is involved in the response of neutrophils to chemoattractants. PMID- 3338995 TI - A comparison of the geminate recombination kinetics of several monomeric heme proteins. AB - The geminate rate constants for CO, O2, NO, methyl, ethyl, n-propyl, and n-butyl isocyanide rebinding to soybean leghemoglobin and monomeric component II of Glycera dibranchiata hemoglobin were measured at pH 7, 20 degrees C using a dye laser with a 30-ns square-wave pulse. The results were compared to the corresponding parameters for sperm whale myoglobin and the isolated alpha and beta subunits of human hemoglobin (Olson, J.S., Rohlfs, R.J., and Gibson, Q.H. (1987) J. Biol. Chem., 262, 12930-12938). The rate-limiting step for O2, NO, and isonitrile binding to all five proteins is ligand migration up to the initial geminate state, and the rate of this process determines the overall bimolecular association rate constant for these ligands. In contrast, iron-ligand bond formation limits the overall bimolecular rate for CO binding. The distal pockets in leghemoglobin and in Glycera HbII are approximately 10 times more accessible kinetically to diatomic ligands than that in sperm whale myoglobin. This difference accounts for the much larger association rate constants (1-2 x 10(8) M 1 s-1) that are observed for O2 and NO binding to leghemoglobin and Glycera HbII. The rates of isonitrile migration through leghemoglobin are also very large and indicate a very fluid or open distal structure near the sixth coordination position. In contrast, there is a marked decrease in the rate of migration up to and away from the sixth coordination position in Glycera HbII with increasing ligand size. These results were also used to interpret previously published rate constants and quantum yields for the high (R) and low (T) affinity states of human hemoglobin. In contrast to the differences between the monomeric proteins, the differences between the CO-, O2-, and NO-binding parameters for R and T state hemoglobin appear to be due to a decrease in the geminate reactivity of the heme iron atom, with little or no change in the accessibility of the distal pocket. PMID- 3338996 TI - Non-transferrin-bound iron uptake by rat liver. Role of membrane potential difference. AB - Non-transferrin-bound iron is efficiently cleared from serum by the liver and may be primarily responsible for the hepatic damage seen in iron-overload states. We tested the hypothesis that transport of ionic iron is driven by the negative electrical potential difference across the liver cell membrane. Extraction of 55Fe-labeled ferrous iron (1 microM) from Krebs bicarbonate buffer by the perfused rat liver was continuously monitored as the transmembrane potential difference (measured using conventional microelectrodes) was altered over the physiologic range by isosmotic ion substitution. Resting membrane potential in Krebs bicarbonate buffer was -28 +/- 1 mV. Perfusion with 1 microM ferrous iron caused a reversible 3 +/- 1 mV depolarization, and higher concentrations of iron caused even greater depolarization. Conversely, depolarization of the liver cells consistently reduced iron extraction. Replacement of sodium with potassium (70 mM) or choline (131 mM) depolarized the hepatocytes to -15 and -20 mV and decreased iron extraction by 28 and 31%, respectively. Perfusion with bicarbonate free solutions containing tricine buffer (10 mM) reduced the membrane potential to -23 mV and reduced iron extraction by 18%. In contrast, the high basal extraction of iron (91.1 +/- 1.4%) was not further increased by substitution of nitrate for chloride (-46 mV) or infusion of glucagon (-34 mV). All effects were reversible, suggesting that perfusion with 1 microM iron produced little toxicity. These findings are consistent with an electrogenic transport mechanism for uptake of non-transferrin-bound iron that is driven by the transmembrane potential difference. PMID- 3338997 TI - Heteronuclear NMR studies of cobalamins. 31P NMR observations of cobalamins bound to a haptocorrin from chicken serum. AB - A vitamin B12-binding protein (haptocorrin) from chicken serum has been purified to homogeneity by photodissociative affinity chromatography and characterized by gel electrophoresis and UV-visible spectrophotometry of its aquocobalamin, hydroxocobalamin, and cyanocobalamin complexes. The haptocorrin is a glycoprotein with a molecular mass of about 70 kDa and a protein moiety of about 40 kDa. 31P NMR resonances of the haptocorrin-cobalamin complexes are relatively broad singlets (with or without proton decoupling) shifted downfield by 0.7-1.0 ppm from the position of the free cobalamin resonances. From the line width data, the relaxation of the phosphorus nucleus is found to be dominated by chemical shift anisotropy with a very minor (13%) component from dipolar interaction with the two nearest neighbor protons. The rotational correlation time of the haptocorrin at 25 degrees C is estimated to be 85 ns and the activation energy for rotational correlation 3.9 +/- 0.3 kcal mol-1. The downfield shift of the 31P resonances of cobalamins upon binding to the haptocorrin cannot be due to hydrogen bonding phosphodiester moiety or displacement of the axial base by a group on the protein. Calculations also show that the downfield shift is very unlikely to be due to dipolar deshielding of the phosphorus nucleus by the ring current of an aromatic residue of the protein. It is concluded that the downfield shift of the 31P resonance must be due to sterically induced changes in phosphodiester conformation which may, or may not, involve steric compression of the axial Co-N bond. PMID- 3338998 TI - On the substrate specificity of rat liver phospholipase A1. AB - The substrate specificity of purified phospholipase A1 was studied using mixed micelles of phospholipid and Triton X-100. The kinetic analysis employed determined Vmax, Ks (a dissociation constant for the phospholipase A1-mixed micelle complex), and Km (the Michaelis constant for the catalytic step which reflects the binding of the enzyme to the substrate in the interface). The order of Vmax values was phosphatidic acid greater than phosphatidylethanolamine greater than phosphatidylcholine greater than phosphatidylserine. The order of Ks values was phosphatidylcholine greater than phosphatidylethanolamine greater than phosphatidic acid greater than phosphatidylserine; the order of Km values was phosphatidic acid greater than phosphatidylethanolamine = phosphatidylserine greater than phosphatidylcholine. When present together, phosphatidylcholine inhibited the hydrolysis of phosphatidylethanolamine but phosphatidylethanolamine did not affect the hydrolysis of phosphatidylcholine. Sphingomyelin, phosphatidylcholine plasmalogen, and phosphatidylethanolamine plasmalogen had no effect on the hydrolysis of phosphatidylethanolamine. The effects of the reaction products, lysolipids and/or fatty acids, were also considered for their influence on phosphatidylethanolamine hydrolysis catalyzed by phospholipase A1. Free fatty acid was found to inhibit, whereas lysophospholipids stimulated hydrolysis of phosphatidylethanolamine. In a mixture of 1,2- and 1,3-diacylglycerides in mixed micelles, only the acyl chain at the sn-1 position of the 1,2 compound was hydrolyzed. Surface charge did not modulate the hydrolysis of phosphatidylcholine vesicles or mixed micelles. In conclusion, it is hypothesized that steric hindrance at position 3 of the glycerol regulates substrate binding in the active site and that an acyl group in position 1 is favored over a vinyl ether linkage for binding. PMID- 3338999 TI - The 6R-oxygenase activity of arachidonate 5-lipoxygenase purified from porcine leukocytes. AB - Arachidonate 5-lipoxygenase purified from porcine leukocytes was incubated with (5S)-hydroperoxy-6,8,11,14-eicosatetraenoic acid. In addition to degradation products of leukotriene A4 (6-trans-leukotriene B4 and its 12-epimer and others), (5S,6R)-dihydroperoxy-7,9,11,14-eicosatetraenoic acid was produced as a major product especially when the incubation was performed on ice rather than at room temperature. The amount of the (5S,6R)-dihydroperoxy acid was close to the total amount of leukotriene A4 degradation products. Under the anaerobic condition, production of the (5S,6R)-dihydroperoxy acid was markedly reduced. 5-Hydroxy 6,8,11,14-eicosatetraenoic acid could be a substrate of the enzyme and was transformed predominantly to a compound identified as (5S)-hydroxy-(6R) hydroperoxy-7,9-trans-11,14-cis-eicosatetraenoic acid at about 1-2% rate of arachidonate 5-oxygenation. These findings indicated that the purified 5 lipoxygenase exhibited a 6R-oxygenase activity with (5S)-hydroxy and (5S) hydroperoxy acids as substrates. The 6R-oxygenase activity, like the leukotriene A synthase activity, was presumed to be an integral part of 5-lipoxygenase because it required calcium and ATP and was affected by selective 5-lipoxygenase inhibitors. PMID- 3339000 TI - Candidate glycophospholipid precursor for the glycosylphosphatidylinositol membrane anchor of Trypanosoma brucei variant surface glycoproteins. AB - Trypanosoma brucei variant surface glycoproteins are apparently synthesized with a hydrophobic carboxyl-terminal peptide that is cleaved and replaced by a complex glycosylphosphatidylinositol membrane anchor within 1 min of the completion of polypeptide synthesis. The rapidity of this carboxyl-terminal modification suggests the existence of a prefabricated core glycolipid that would be transferred en bloc to the variant surface glycoprotein polypeptide. We report the purification and chemical characterization of a glycolipid from T. brucei that has properties consistent with a role as a variant surface glycoprotein glycolipid donor. This candidate glycolipid precursor has been defined by thin layer chromatography of extracts of trypanosomes metabolically labeled with radioactive myristic acid, ethanolamine, glucosamine, mannose, and phosphate and by enzymatic, chemical, and gas chromatographic-mass spectrometric analysis. Mild alkali released 100% of the myristic acid, and reaction with phospholipase A2 released 50%. Nitrous acid deamination generated dimyristylphosphatidylinositol, and periodate oxidation released phosphatidic acid. Treatment of purified glycolipid with phosphatidylinositol-specific phospholipase C released dimyristylglycerol and a water-soluble glycan that was sized on Bio-Gel P-4 columns. The candidate precursor contained mannose, myristic acid, phosphate, and ethanolamine with an unsubstituted amino group, but not galactose. PMID- 3339001 TI - Antifolate-resistant Chinese hamster cells. Molecular basis for the biochemical and structural heterogeneity among dihydrofolate reductases produced by drug sensitive and drug-resistant cell lines. AB - Nucleotide sequence analysis of a cDNA clone shown to direct the synthesis in Escherichia coli of a pI 6.5 form of dihydrofolate reductase (DHFR) with an apparent molecular weight of 21,000 has clarified the allelic nature of the DHFR genes present in the Chinese hamster lung cell line DC-3F. By comparison with other cDNAs encoding different forms of DHFR produced by these cells or by antifolate-resistant sublines derived from them (Melera, P.W., Davide, J.P., Hession, C.A., and Scotto, K.W (1984) Mol. Cell. Biol. 4, 38-48) and with the use of transcription vectors to generate homogeneous populations of specific DHFR mRNAs for subsequent translation in vitro, we demonstrate that, with respect to the proteins they encode, these alleles differ only at amino acid position 95; a conversion of Asp----Asn at this position is solely responsible for the electrophoretic mobility and pI differences between the Mr 21,000 pI 6.5 and Mr 20,000 pI 6.7 forms of the enzyme. We also show that the conversion of Leu to Phe at position 22 of the Mr 21,000 pI 6.5 enzyme results in a mutant form whose catalytic activity is equal to or greater than normal, but whose IC50 for methotrexate is 85 microM. Additionally, the in vitro translation experiments show that the minor pI forms of DHFR known to exist in Chinese hamster lung cells are generated by a translational or post-translational modification step. Preliminary evidence suggests that this modification may result from an acetylation of the N terminus of the protein. PMID- 3339002 TI - Complex ganglioside expression and tetanus toxin binding by PC12 pheochromocytoma cells. AB - Ganglioside expression and tetanus toxin binding were studied in the rat pheochromocytoma cell line PC12. Seven ganglioside species were readily detected in extracts of PC12 cells; two were identified as tri- and tetrasialogangliosides, which are common brain constituents but unusual components of neuronal cell lines. Carbohydrate composition, acid and enzyme hydrolyses, and mass spectral analysis revealed that the major species is GT 1b, a predominant mammalian brain ganglioside previously reported to support high affinity tetanus toxin binding (Rogers, T. B., and Snyder, S. H. (1981) J. Biol. Chem. 256, 2402-2407). Direct binding of 125I-tetanus toxin to PC12 gangliosides on TLC plates revealed selective binding to the tri- and tetrasialogangliosides. Radioiodinated toxin also bound with high affinity to intact PC12 cells or their isolated membranes. The binding affinity (Kd = 1.25 nM), density of receptors (Bmax = 238 pmol/mg of membrane protein), and dependence on pH, ionic strength, and temperature were similar to those previously reported for toxin binding to rat brain synaptic membranes. Differentiation of PC12 cells caused an increase in expression of the tri- and tetrasialogangliosides and a closely matched increase in tetanus toxin binding to cell membranes. These data provide evidence that complex gangliosides may act as tetanus toxin receptors, and demonstrate the utility of the PC12 cell line for studies of tetanus toxicity and complex ganglioside expression. PMID- 3339003 TI - Human melanoma antigen O-acetylated ganglioside GD3 is recognized by Cancer antennarius lectin. AB - A lectin that can specifically bind to O-acetylsialic acids, found in glycoproteins and gangliosides, was purified to homogeneity from a crab Cancer antennarius (crab lectin) (Ravindranath, M. H., Higa, H. H., Cooper, E. L., and Paulson, J. C. (1985) J. Biol. Chem. 260, 8850-8856; Correction (1986) J. Biol. Chem. 261, 1983; Ravindranath, M. H., and Paulson, J. C. (1987) Methods Enzymol. 138, 520-527). We tested lectin binding to human melanoma cell lines to identify O-acetylsialylated gangliosides on the melanoma cell surface. The highest degree of binding of the crab lectin was demonstrated on a melanoma cell line, UCLASO M25. To confirm that the binding was due to O-acetylsialic acid in the alkali labile gangliosides, the gangliosides were isolated and purified from M25 cells and individually coated onto sheep asialoerythrocytes, which served as targets in an agglutination assay using the lectin. The crab lectin agglutinated the asialo sheep erythrocytes coated with alkali-labile gangliosides, but the lectin failed to agglutinate the asialoerythrocytes coated with GM3, GD3, and base-treated gangliosides. Subsequently, the purified alkali-labile M25 ganglioside was base treated and applied to TLC, and we found that it was converted to a slower migrating species identical to the disialolactosylceramide (GD3). These results indicate that O-acetyl GD3 expressed on the melanoma cell surface is recognized by the lectin. Because O-acetyl GD3 is not expressed on human normal tissues, we examined the capability of O-acetyl GD3 to induce immune responses in man. Sera from patients with melanoma were tested against M25 cells in an immuneadherence assay, and those positive to the M25 cell line were further tested for specificity to O-acetyl gangliosides. The presence of autoantibodies to O-acetyl GD3 in melanoma sera was confirmed by blocking of the antigen sites on M25 cells by the lectin or preabsorption of the sera with erythrocytes bearing O-acetyl gangliosides. The data provide evidence that O-acetyl-GD3 may represent an important tumor marker for detection and treatment of human melanoma. PMID- 3339004 TI - The pH-dependent conformational change of diphtheria toxin. AB - Labeling by a hydrophobic photoactivatable reagent and limited proteolysis have been used to study conformational changes of diphtheria toxin related to its pH dependent membrane insertion and translocation. TID (3-(trifluoromethyl)-3-(m [125I]iodophenyl)diazirine) labels diphtheria toxin at pH 5 much more efficiently than at pH 7, both in the presence and absence of lipid vesicles. In the absence of membranes, the extent of labeling is greater and the pH dependence is stronger. As analyzed on sodium dodecyl sulfate-polyacrylamide gels and by high pressure liquid chromatography, both the A- and B-subunits and most of the cyanogen bromide fragments of the toxin are labeled by TID at acid pH. The products of trypsin cleavage of diphtheria toxin at pH 5 are different from those seen at neutral pH. Trypsin-susceptible sites were identified by gel electrophoresis of the trypsin fragments, combined with electrophoresis and high pressure liquid chromatography of CNBr digests of trypsin-treated toxin. At neutral pH, the main sites of digestion are at the junction between the A- and B fragments and near the NH2 terminus of the A-fragment. At pH 5.2, these sites are less efficiently cut, and new sites appear near the NH2 terminus of the B fragment, in an amphipathic portion of the sequence. Thus, even in the absence of membranes, acid pH induces a significant conformational change in diphtheria toxin. This change involves burial of some previously accessible sites, exposure of previously inaccessible sites, and the formation of hydrophobic regions over an extensive portion of the polypeptide chain. PMID- 3339005 TI - Human gastric lipase: a sulfhydryl enzyme. AB - One sulfhydryl group was modified per mol of native human gastric lipase after incubation at pH 8.0 with 5,5'-dithiobis(2-nitrobenzoic acid) for 18 h or with 4,4'-dithiopyridine for 100 min. With both reagents a direct correlation was found between the modification of one sulfhydryl group and the loss of human gastric lipase activity. Incubation of human gastric lipase with a new hydrophobic sulfhydryl reagent dodecyldithio-5-(2-nitrobenzoic acid) in 30-fold molar excess, at pH 3.0, 5.0, and 8.0, induced immediate and complete human gastric lipase inactivation. Unlike 5,5'-dithiobis(2-nitrobenzoic acid) and 4,4' dithiopyridine, dodecyldithio-5-(2-nitrobenzoic acid) almost instantaneously stopped the course of tributyrin hydrolysis by human gastric lipase. Human gastric lipase can thus be said to be a sulfhydryl enzyme. PMID- 3339006 TI - Behavior of antithrombin III isoforms on immobilized heparins. Evidence that the isoforms bind to different numbers of low-affinity heparin sites. AB - Antithrombin III exists in plasma as major and minor isoforms differing in affinity for heparin. The nature of the binding of each purified isoform to immobilized heparins was investigated. Unfractionated, mixed-affinity heparin bound each isoform with both high affinity and concentration-dependent low affinity. The isoforms were resolved when filtered through low-affinity heparin (heparin repeatedly passed over immobilized antithrombin III) columns. Following chemical modification of a specific tryptophan residue required for heparin binding, each isoform failed to bind to either low-affinity or mixed-affinity heparin-agarose, but elution of the modified higher-affinity isoform was retarded on both gels. Because the modified lower-affinity isoform eluted with the similarly sized bovine serum albumin in these experiments, the difference in isoform affinity for heparin appears to be the result of a unique, secondary heparin-binding site in the higher-affinity isoform that can bind a heparin site with low affinity for antithrombin III. This interpretation was supported by the chromatographic behavior of the isoforms on mixed-affinity agarose during reverse gradient elution. Two other populations of each of the tryptophan-modified isoforms were identified. Since these isoforms bound tightly to mixed-affinity heparin-agarose but eluted at lower salt concentrations than the corresponding unmodified isoforms, both isoforms may contain additional secondary sites that interact weakly with heparin. A general model of heparin-antithrombin III interaction is proposed in which a high-affinity heparin site initially interacts with a primary site on antithrombin III. The subsequent conformational change leads to a cooperative, entropy-driven association between secondary sites on the protein and low-affinity sites on heparin, stabilizing antithrombin III in its activated form. PMID- 3339007 TI - Modulation of red cell band 4.1 function by cAMP-dependent kinase and protein kinase C phosphorylation. AB - Human erythrocyte protein 4.1 is phosphorylated in vivo by several protein kinases including protein kinase C and cAMP-dependent kinase. We have used cAMP dependent kinase purified from red cells and protein kinase C purified from brain to test the effects of phosphorylation on band 4.1 function. In solution, each kinase catalyzed the incorporation of 1-4 mol of PO4/mol of band 4.1. Phosphorylation of band 4.1 by each kinase resulted in a significant (50-80%) reduction in the ability of band 4.1 to promote spectrin binding to F-actin. Direct measurement of spectrin-band 4.1 binding showed that phosphorylation by each kinase also caused dramatic reduction in this association. Phosphorylation of band 4.1 by each kinase for increasing time periods enabled us to demonstrate an approximately linear inverse relationship between PO4 incorporation into band 4.1 and spectrin binding. These results show that phosphorylation of band 4.1 by cAMP-dependent kinase and protein kinase C may be central to the regulation of red cell cytoskeletal organization and membrane mechanical properties. PMID- 3339008 TI - Platelet-neutrophil interactions. (12S)-hydroxyeicosatetraen-1,20-dioic acid: a new eicosanoid synthesized by unstimulated neutrophils from (12S)-20 dihydroxyeicosatetraenoic acid. AB - In the course of a cell-cell interaction, 12-HETE (12-hydroxy-5,8,10,14 eicosatetraenoic acid), the arachidonic acid lipoxygenase product released from stimulated platelets, is metabolized by a cytochrome P-450 enzyme system in unstimulated neutrophils to 12,20-DiHETE (12,20-dihydroxy-5,8,10,14 eicosatetraenoic acid). This report describes time-dependent formation of a new eicosanoid by unstimulated neutrophils exposed to 12-HETE, which is more polar than 12,20-DiHETE (reversed-phase high performance liquid chromatography). Time course studies indicated that the precursor compound of this new eicosanoid was 12,20-DiHETE. This was determined by incubation of purified 12,20-DiHETE with neutrophils, which resulted in a progressive decrease in 12,20-DiHETE as formation of the polar metabolite increased. In the absence of neutrophils, 12,20 DiHETE was quantitatively unchanged. The new metabolite of 12,20-DiHETE was identified as 12-hydroxyeicosatetraen-1,20-dioic acid, based upon its UV spectrum, co-chromatography with a chemically synthesized standard in both high performance liquid chromatography and thin layer chromatography systems, and gas chromatography-mass spectrometry. Formation of 12-HETE-1,20-dioic acid was partially inhibited by 20-hydroxy-LTB4. This indicated that the neutrophil dehydrogenase responsible for further metabolism of 12,20-DiHETE may also be involved in conversion of 20-hydroxy-LTB4 to 20-carboxy-LTB4. The 12,20-DiHETE dehydrogenase enzyme system specifically requires NAD as cofactor and has subcellular components in both cytosolic and microsomal fractions which are synergistic in their activity. These results provide additional evidence for the occurrence of multicellular metabolic events during hemostasis, thrombosis, and the inflammatory response. PMID- 3339009 TI - Photoaffinity labeling of the oxysterol receptor. AB - A cytosolic receptor protein for oxygenated sterols, postulated to be involved in the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol biosynthesis, can be labeled covalently by photoactivation of 7,7'-azo-[5,6 3H]cholestane-3 beta,25-diol. Other compounds tested for their potential as photoaffinity reagents were: 25-hydroxycholesta-4,6-dien-3-one, 3 beta,25 dihydroxycholest-5-en-7-one, and 3 beta-hydroxycholesta-8(14),9(11)-dien-15-one. These sterols did not bind to the receptor with adequate affinity, were not readily photolyzed, or did not react covalently with the receptor during photolysis. The successful photoaffinity label, 7,7'-azocholestane-3 beta,25 diol, binds to the receptor with high affinity (Kd = 9.1 nM). After activation of the partially purified oxysterol-receptor complex with UV light (greater than 300 nm), several covalently labeled proteins were found upon sodium dodecyl sulfate gel electrophoresis. Labeling of one protein, Mr approximately 98,000, was much reduced when the binding reaction was carried out in the presence of an excess of unlabeled oxysterol. Under the reaction conditions investigated so far, approximately 1% of the specifically bound sterol was covalently linked after photolysis. These results are consistent with previous information suggesting that the Mr of the receptor subunit is approximately 97,000. The covalent labeling of the receptor reported herein should facilitate its further purification and characterization. PMID- 3339010 TI - Kinetic studies on partially liganded species of carboxyhemoglobin: alpha 2 CO beta 2 and alpha 2 beta 2CO. AB - The valency hybrids of Hb A, alpha 2CO beta 2+, and alpha 2+ beta 2CO have been prepared by a new high pressure liquid chromatography method, and the kinetics of their CO-combination and dissociation reactions have been studied by double mixing and microperoxidase methods. Both reactions are biphasic. The slow phase in CO-combination and the fast phase in CO-dissociation are due to the reactions of alpha CO2 beta T2 or alpha 2 beta 2CO,T. The fast phase in CO-combination reaction has two components, one due to the dimers of the hybrid and the other due to the R-state tetramer. Immediately after the reduction of the valency hybrids, the overall system is represented by the equation: 2 alpha CO beta in equilibrium alpha 2CO beta 2R in equilibrium alpha 2CO beta 2T or (formula: see text) If the solutions are aged for 3-11 s, the R-state population is reduced gradually to a very small size, and the main species after 11 s of aging are dimers and T-state tetramers. Analysis of the kinetic data indicates slow R in equilibrium T equilibria in the absence of phosphates and significant dissociation of the T-state tetramer. It is concluded that the subunit contacts alpha 1-beta 2 (or alpha 2-beta 1) are impaired seriously in the hybrids. Very slow R in equilibrium T relaxation makes these hybrids unlikely intermediates in the sequential binding of CO to Hb tetramer. PMID- 3339011 TI - Mechanism of formation of bound alpha-iminoglutarate from alpha-ketoglutarate in the glutamate dehydrogenase reaction. A chemical basis for ammonia recognition. AB - Two mechanisms have been postulated for the formation of bound alpha iminoglutarate intermediate during the glutamate dehydrogenase-catalyzed reductive amination of alpha-ketoglutarate; one involves the nucleophilic attack of ammonia on a covalently bound Schiff base in the enzyme-NADPH-alpha ketoglutarate complex, and the other involves the reaction of ammonia with the carbonyl group of alpha-ketoglutarate in the ternary complex. We have measured the rates of carbonyl oxygen exchange in the complex to unambiguously distinguish between these two mechanisms. We find that the loss of label in the carbonyl oxygen-labeled ternary complex is at least 10(5) times slower than the rate of the reductive amination reaction. Therefore, the former mechanism cannot be operative. We also find that (i) the carbonyl oxygen exchange in free alpha ketoglutarate proceeds without any significant catalysis by its gamma-carboxylate group; (ii) this exchange reaction has energy parameters which are comparable to those observed for the hydration of simple aliphatic ketones; and (iii) the carbonyl oxygen exchange in bound alpha-ketoglutarate is slower than that in the free keto acid over a wide pH range. We conclude that the oxygen exchange in the free and bound alpha-ketoglutarate must occur via a gem-diol intermediate. The observation that the enzyme inhibits the reaction of water with alpha ketoglutarate while it catalyzes the reaction of ammonia with the same keto acid points to an extraordinary recognition of ammonia by the enzyme. We interpret this observation by assuming that the enzyme-NADPH-alpha-ketoglutarate complex exists in two forms, a predominant form which is produced rapidly upon mixing the components together and an unstable form which is produced in trace amounts from the predominant form via a gem-diol intermediate. These two forms are presumed to differ in the spatial relationship of the carbonyl group to the enzyme functional groups. The carbonyl group in the unstable form is assumed to be surrounded by the same enzyme groups as the iminium ion is in the bound iminoglutarate complex. We ascribe the remarkable catalysis of the ammonia reaction and the inhibition of the water reaction by the enzyme to the opposing interactions of the iminium and carbonyl groups with these surrounding enzyme groups. PMID- 3339012 TI - Site density of the sodium-calcium exchange carrier in reconstituted vesicles from bovine cardiac sarcolemma. AB - The site density of the Na2+-Ca2+ exchanger in bovine cardiac sarcolemma was estimated from measurements of the fraction of reconstituted proteoliposomes exhibiting exchange activity. Sarcolemmal vesicles were solubilized with 1% Triton X-100 in the presence of either 100 mM NaCl or 100 mM KCl; after a 20-40 min incubation period on ice, sufficient KCl, NaCl, CaCl2, and soybean phospholipids were added to each extract to give final concentrations of 40 mM NaCl, 120 mM KCl, 0.1 mM CaCl2, and 10 mg/ml phospholipid. These mixtures were then reconstituted into proteoliposomes, and the rate of 45Ca2+ isotopic exchange was measured under equilibrium conditions. Control studies showed that Na+-Ca2+ exchange activity was completely lost if Na+ was not present during solubilization. The difference in 45Ca2+ uptake between vesicles initially solubilized in the presence or absence of NaCl therefore reflected exchange activity and corresponded to 3.1 +/- 0.3% of the total 45Ca2+ uptake by the entire population of vesicles, as measured in the presence of the Ca2+ ionophore A23187. Assuming that each vesicle with exchange activity contained 1 molecule of the Na+-Ca2+ exchange carrier, a site density of 10-20 pmol/mg of protein for the exchanger was calculated. The Vmax for Na+-Ca2+ exchange activity in the proteoliposomes was approximately 20 nmol/mg of protein.s which indicates that the turnover number of the exchange carrier is 1000 s-1 or more. Thus, the Na+ Ca2+ exchanger is a low density, high turnover transport system. PMID- 3339013 TI - Trapping of nitric oxide produced during denitrification by extracellular hemoglobin. AB - A spectrophotometric method has been developed that uses extracellular hemoglobin (Hb) to trap nitric oxide (NO) released during denitrification as nitrosyl hemoglobin (HbNO). The rate of complexation of NO with Hb is about at the diffusion controlled limit for protein molecules and the product, HbNO, is essentially stable. Hb was added to an anaerobic bacterial suspension and denitrification was initiated with either KNO2 or KNO3. HbNO formation was observed for six species of denitrifying bacteria and showed isosbestic points at 544, 568, and 586 nm. Cellular NO production, presumably by nitrite reductase, was kinetically distinct from the much slower chemical reaction of Hb with KNO2 to form methemoglobin and HbNO. The rate of HbNO formation was proportional to cell density, essentially independent of pH from 6.8 to 7.4, nearly zero order in [Hb] and, at least with Paracoccus denitrificans, strongly inhibited by rotenone and antimycin A. The Cu chelator, diethyldithiocarbamate, had no effect on HbNO formation by Pa. denitrificans, but abolished that by Achromobacter cycloclastes which uses a Cu-containing nitrite reductase known to be inactivated by the chelator. HbNO formation did not occur with non-denitrifying bacteria. The stoichiometry at high [Hb] for conversion of Hb to HbNO was 1.3-1.8 KNO2 per Hb for Pa. denitrificans, Pseudomonas aeruginosa, and A. cycloclastes and about 3.4 for Pseudomonas stutzeri. The former range of values corresponds to a partition of about 2 N atoms in 3 toward trapping and 1 in 3 toward reduction on the pathway to N2. Nitrogen not trapped appeared largely as N2O in presence of acetylene. The results are consistent with a model in which NO is a freely diffusible intermediate between nitrite and N2O, providing that nitric oxide reductase is or nearly is a diffusion controlled enzyme. PMID- 3339014 TI - Cartilage type IX collagen-proteoglycan contains a large amino-terminal globular domain encoded by multiple exons. AB - Type IX collagen in cartilage consists of molecules composed of three genetically distinct polypeptide subunits. One of the subunits, alpha 2(IX), contains a covalently attached glycosaminoglycan side chain whereas a second subunit, alpha 1(IX), contains a large noncollagenous, amino-terminal domain called NC4. In this report, we describe for the first time the complete primary structure of this noncollagenous domain, based on cloning and sequencing of cDNA and genomic DNA as well as amino acid sequencing of tryptic peptides. Analysis of genomic clones has also allowed determination of the exon structure of NC4. Our results demonstrate that the noncollagenous, amino-terminal domain of alpha 1(IX) chains contains 266 amino acid residues (including the signal peptide) with 5 cysteinyl residues forming two disulfide bridges. The domain is basic with an estimated pI of 9.7, thus supporting the idea that it may participate in ionic interactions with polyanionic glycosaminoglycans in cartilage. Both the sequence and exon structure of the NC4 domain is unique among collagens and there is no obvious homology with the noncollagenous domains of other types of collagen, including the propeptides of fibrillar collagens. PMID- 3339015 TI - Localization and sequence analysis of poly(A) sites generating multiple dihydrofolate reductase mRNAs. AB - The murine dihydrofolate reductase (DHFR) gene gives rise to multiple polyadenylated mRNAs displaying heterogeneity in the length of the 3' untranslated region. These species are present in the cytoplasm at levels that vary over 2 orders of magnitude, suggesting that certain poly(A) sites are preferred over others. Previous observations have shown that three out of the four major sites of polyadenylation do not display consensus hexanucleotide (AATAAA, ATTAAA) signals. We have further analyzed the sequences involved in directing multiple polyadenylation events on the DHFR gene by focusing our attention on the 4.1- and 5.6-kilobase mRNAs, the lowest abundance DHFR species observed on RNA blot analysis. Identification and sequence analysis of the poly(A) addition sites corresponding to these species revealed appropriately positioned consensus hexanucleotide signals; additional nearby poly(A) sites were also detected which apparently do not use consensus hexanucleotides to direct poly(A) addition to DHFR mRNAs of relatively lower abundance. We have also identified polyadenylation sites downstream of the 4.1- and 5.6-kilobase sites which display consensus hexanucleotide signals and correspond to messenger species too rare for detection by routine RNA blot analysis. Our data bring to 11 the number of known functional poly(A) addition sites associated with the DHFR gene. PMID- 3339016 TI - Purified protein kinase C phosphorylates a 47-kDa protein in control neutrophil cytoplasts but not in neutrophil cytoplasts from patients with the autosomal form of chronic granulomatous disease. AB - The neutrophil activators phorbol 12-myristate 13-acetate (PMA), formyl-methionyl leucyl-phenylalanine, serum-treated zymosan, and IgG-coated latex cause an increase in protein phosphorylation in human neutrophil cytoplasts, concomitantly with an increase in oxygen consumption. After sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography, phosphorylation was apparent in many proteins, must abundantly in 42-, 47-, 50-, 60-, and 80-kDa proteins. In neutrophil cytoplasts from autosomal chronic granulomatous disease (CGD) patients that were stimulated with PMA, the phosphorylation of a 47-kDa protein is absent. The localization of this protein in PMA-activated control cytoplasts is mainly in the cytosol and, to a lower and more variable extent, in the membrane. After addition of purified protein kinase C to lysates of nonstimulated control cytoplasts, phosphorylation occurred at the 47-kDa level in both the cytosol and the membrane fraction. With lysates of autosomal CGD cytoplasts, in vitro phosphorylation of the 47-kDa protein was completely absent. After separation of cytoplast proteins on a sodium dodecyl sulfate-polyacrylamide gel and excision of the 47-kDa protein(s), phosphorylation of the isolated 47-kDa band was observed in the presence of purified protein kinase C. This reaction was again absent when autosomal CGD cytoplasts were used as starting material. Our studies have identified the 47-kDa protein in neutrophil cytoplasts as a true substrate for protein kinase C and indicate that the defect in phosphorylation at the 47-kDa level in autosomal CGD cytoplasts is due to a defective protein. PMID- 3339017 TI - The microheterogeneity of androgen-binding protein in rat serum and epididymis is due to differences in glycosylation of their subunits. AB - The microheterogeneity of androgen-binding protein (ABP) from rat serum and epididymis was examined by subjecting purified native or deglycosylated preparations to analysis by one- or two-dimensional polyacrylamide gel electrophoresis (PAGE) followed by electrophoretic transfer to nitrocellulose and immunochemical localization. Analysis of native ABP by one-dimensional sodium dodecyl sulfate-PAGE confirmed earlier observations that it is composed of subunits and that the subunits of serum ABP had higher apparent molecular weights than those of epididymal ABP. Treatment with neuraminidase, N-glycanase, or O glycanase, alone or in combination, resulted in decreases in the apparent molecular weight of the subunits. These analyses indicated that terminal sialic acid residues and Asn-linked oligosaccharides were present on both subunits of ABP from the two sources. The fact that the greatest reduction in the Mr of the heavy subunit occurred following treatment with all three enzymes provides evidence that O-linked sugars are present on it. While enzyme treatment did not result in the appearance of a single subunit, chemical deglycosylation did (Mr 39,600). The carbohydrate composition of the heavy and light subunits of intact serum and epididymal ABP was 22 and 9% and 19 and 8%, respectively. Analysis by two-dimensional PAGE indicated that both subunits of the ABPs were composed of isoelectric variants. Although ABP from the two sources had several variants in common, differences were also observed. Treatment of the ABPs with the enzymes resulted in a shift of the pI values to a more basic pH range, indicating that carbohydrate removal also removed charged moieties. The most dramatic shift in the pI values of the isoforms occurred when O-glycanase was present in the enzyme mixture, providing further evidence for the presence of O-linked oligosaccharides on ABP. Isoelectric variants were present even after chemical deglycosylation of ABP. PMID- 3339018 TI - The subcellular localization of apomucin and nonreducing terminal N acetylgalactosamine in porcine submaxillary glands. AB - Antibodies prepared against enzymatically deglycosylated porcine submaxillary gland mucin (apomucin), which were unreactive with native mucin and its partially deglycosylated derivatives, were used to immunolocalize apomucin in situ. Electron microscopy of sections of Lowicryl K4M-embedded tissue reacted successively with antibodies and protein A-gold complexes showed apomucin exclusively in mucous cells within the rough endoplasmic reticulum, transitional elements of the endoplasmic reticulum, and vesicles at the cis side of the Golgi apparatus. The Golgi apparatus, forming mucous droplets, and mucous droplets contained no apomucin. Although the rough endoplasmic reticulum contained most of the apomucin in mucous cells, some cisternae of the endoplasmic reticulum and the nuclear envelope were devoid of apomucin. Examination of tissue sections treated with the glycosidases used to prepare apomucin revealed immunolabel for apomucin throughout the secretory pathway. Colloidal gold coated with Helix pomatia lectin was used to detect nonreducing N-acetylgalactosamine residues. In mucin-producing cells lectin-gold was found in the mucous droplets, the forming mucous droplets, and throughout the Golgi apparatus but mostly in the cis portion of this organelle. In tissue sections reacted successively with lectin-gold and anti apomucin/protein A-gold, both types of gold complex could be found in the cis side of the Golgi apparatus. These data indicate that the O-glycosylation of mucin is a posttranslational event that occurs in the Golgi apparatus and begins in the cis side of the Golgi apparatus. PMID- 3339019 TI - Low pH-induced release of diphtheria toxin A-fragment in Vero cells. Biochemical evidence for transfer to the cytosol. AB - When Vero cells with surface-bound 125I-labeled, nicked diphtheria toxin were exposed to pH 4.5, two polypeptides of Mr 20,000 and 25,000 became protected against externally applied Pronase E. The 20-kDa polypeptide appears to be the toxin A-fragment, whereas the 25-kDa polypeptide must be derived from the B fragment. Permeabilization of the cells with saponin allowed efflux of the 20-kDa fragment to occur, whereas most of the 25-kDa polypeptide remained associated with the cells. A number of compounds and conditions which protect cells against diphtheria toxin prevented the protection against Pronase E. Protection of the 25 kDa polypeptide occurred even when the transmembrane proton gradient (delta pH) was dissipated by acidification of the cytosol, whereas protection and release of the A-fragment were prevented under these conditions. Electrical depolarization and ATP depletion of the cells did not inhibit protection and release of the A fragment. The data indicate that delta pH is required for the transfer of the A fragment to the cytosol, whereas the insertion of part of the B-fragment into the membrane occurs at low pH, even in the absence of a delta pH. PMID- 3339020 TI - Cell density-dependent expression of chondroitin sulfate proteoglycan in cultured human monocytes. AB - Monocytes were isolated and established in vitro at different cell densities. The incorporation of [35S]sulfate into macromolecules in monocytes (day 1 in culture) and monocyte-derived macrophages (day 5 in culture) was found to increase with decreasing cell density in approximately the same way in both day 1 and day 5 cell cultures. [35S]Sulfate was found to be incorporated almost exclusively into chondroitin sulfate proteoglycan (CSPG) in both high and low density monocyte and monocyte-derived macrophage cultures. The molecular size of the [35S]CSPGs produced by the high and low cell density cultures were not found to differ as judged by gel chromatography elution patterns. The molecular size and the structure of the glycosaminoglycan chains were found to be almost similar in high and low density day 1 and day 5 cultures. Only a small degree of proteoglycan degradation could be observed in both high and low density cultures. Furthermore, cell density-dependent differences in CSPG biosynthesis could be observed already 2 h after the establishment of the cultures, indicating that a process of "down regulation" in high density cultures was already in operation. The glycosaminoglycan synthesis in high cell density day 1 cultures could be increased slightly following exposure to 0.5 mM benzyl-beta-D-xyloside, but not to the same level as that observed in untreated low cell density cultures. By contrast, the expression of 35S-macromolecules by cells cultured at high cell density for 5 days could be increased by xyloside treatment almost to the same level as that observed in the low density cultures. PMID- 3339021 TI - Evidence for the phosphorylation of a proenkephalin-derived peptide, peptide B. AB - The potential phosphorylation of a proenkephalin-derived peptide, Peptide B, was investigated in primary cultures of bovine adrenal chromaffin cells and fresh adrenal medullary tissue. Cultures were labeled with [32P]phosphate for 24 h and extracts subjected to immunoprecipitation using affinity-purified anti-serum directed against the carboxyl terminus of Peptide B. A 4.6-kDa-labeled peptide was observed in autoradiograms of immunoprecipitates separated by sodium dodecyl sulfate-polyacrylamide electrophoresis; this peptide was not observed when excess antigen was present during the immunoprecipitation. Radioimmunoassay of extracts prepared from adrenal medullary tissue and separated by isoelectric focusing revealed the presence of four isoelectric forms of Peptide B-immunoreactive peptides; these peptides also exhibited Met-enkephalin-Arg-Phe immunoreactivity. The isoelectric points of these peptides (4.5, 4.3, 4.1, and 3.9) were consistent with the predicted pI values for phosphorylated derivatives of Peptide B. Treatment of samples with alkaline phosphatase prior to isoelectric focusing resulted in the conversion of the more acidic forms to the least acidic form. The presence of phosphate in the more acidic peaks was additionally verified by isoelectric focusing of 32P-labeled immunoprecipitates; the pI values of the radioactive peptides corresponded precisely to the peaks of immunoreactivity. In adrenal medullary tissue, the relative contributions of the various phosphorylated species to the total Peptide B immunoreactivity were as follows: unphosphorylated form, 13%; singly phosphorylated, 31%; doubly phosphorylated, 37%; and triply phosphorylated, 17%. Thus more than 85% of the Peptide B molecules present in the bovine adrenal medulla are phosphorylated. PMID- 3339022 TI - Stiffness of compact bone: effects of porosity and density. AB - Stiffness of compact bone is found to be highly and nonlinearly dependent on its porosity, its complement, bone volume fraction and apparent density. Elastic modulus decreases as a power (0.55) of increasing porosity and increases both as a power of increasing bone tissue volume (10.92) and increasing apparent density (7.4). These data indicate that small changes in the amount or density of compact bone tissue exert a more pronounced influence on its stiffness than would similar changes in trabecular bone. PMID- 3339023 TI - Experimental determination of forces transmitted through the patello-femoral joint. AB - Tensions in the quadriceps tendon and infrapatellar ligament were measured as a function of flexion angle in eight cadaver knees using a load cell of a materials tester to determine the quadriceps force and a spring balance to quantify the patellar tendon force. The ratio between the tensions in the quadriceps tendon and the patellar tendon (FQ/FP) ranged from 1.55 at 70 degrees of flexion to 0.86 at 10 degrees of flexion. The patello-femoral joint reaction (PFJR) force for extension against resistance was maximal at 60 degrees. No change in the quadriceps force required to extend the knee occurred with changes of the Q-angle of +/- 5 degrees. This study demonstrates that FQ does not equal FP as several authors have reported (Bandi, 1972; Barry, 1979; Ficat and Hungerford, 1977; Hungerford and Barry, 1979; Reilly and Martens, 1972; Smidt, 1973). Furthermore, the difference in FQ and FP influences both the magnitude and direction of PFJR. Studies that assess the influence of surgical procedures which alter the patello femoral joint or the extensor mechanism must take these differences into account. PMID- 3339024 TI - Network analysis of an arterial tree. AB - The arterial tree of a Sprague-Dawley rat was casted and carefully mapped with the aim of comparing its network characteristics with those suggested by the classical model of an arterial tree. It is shown that if the tree is to be measured accurately, the concept of 'whole vessels' on which the classical model is based must be abandoned since such vessels do not actually exist in the network, nor can they be accurately defined. The concept of 'vessel segments' is proposed instead and its use is demonstrated. A total of 1313 vessel segments in the arterial tree of the rat are mapped and divided into well defined 'levels'. The length and diameter of each segment are measured and the distribution and averages of these at different levels are presented as indicators of the branching characteristics of the tree. PMID- 3339025 TI - Isometric and isokinetic back and arm lifting strengths: device and measurement. AB - This study was conducted to measure isometric (static) and isokinetic (dynamic) back and arm lifting strengths at 20, 60 and 100 cm s-1 of young adults. Ten male and ten female volunteers without a history of back pain participated. The isokinetic lifting task was achieved by controlled motorized dynamic strength tester (DST). A regression analysis and analysis of variance was carried out on the strength data. The peak static strength values were significantly greater from the peak dynamic strength values. The peak dynamic strength was inversely related to the speed of motion. There were significant differences between the dynamic strengths at different stages of lift. PMID- 3339026 TI - A least-squares algorithm for the equiform transformation from spatial marker co ordinates. AB - The present paper describes an algorithm for estimating the translation vector and the rotation matrix of a moving body from noisy measurements on the spatial co-ordinates of at least three non-collinear markers. A sensitivity analysis of the estimated parameters and of the helical axis is presented in terms of characteristics of the marker distribution. The implementation of the proposed algorithm in a FORTRAN-subroutine is appended. PMID- 3339027 TI - The relation between the resultant moments at a joint and the moments measured by an isokinetic dynamometer. AB - Isokinetic dynamometers have frequently been used to determine in vivo properties of human skeletal muscles. In these investigations the moments recorded by the dynamometer were often (implicitly) assumed to be the same as the joint moments produced by muscles. This assumption may have contributed to the conflicting results about in vivo muscle properties of human skeletal muscles that are reported in the literature. The purpose of this paper is to present a method for calculating the resultant joint moments from the moments recorded using a Cybex II dynamometer and to determine the differences between these two moments for some typical exercise conditions. The differences between these these moments are shown to be due to (a) gravitational effects, (b) inertial effects, and (c) non rigidity of the Cybex arm/shank-foot system. The results obtained suggest that the moments recorded using the dynamometer should not be used to derive muscle properties without taking into account the relationship between the resultant joint moments and the moments measured using an isokinetic dynamometer. PMID- 3339028 TI - Pulse velocities in initially stressed arteries. AB - In this short paper, treating the artery as a thick walled cylindrical shell and employing the large deformation theory, an analytical expression for the pulse wave speed is obtained and the effect of lumen pressure and the axial stretch on the wave speed is discussed. Numerical results indicate that although the wave speed increases with inner pressure, it decreases with increasing axial stretch. PMID- 3339029 TI - Biomechanical model calculation of muscle contraction forces: a double linear programming method. AB - This paper presents a novel scheme for the use of linear programming to calculate muscle contraction forces in models describing musculoskeletal system biomechanics. Models of this kind are frequently found in the biomechanics literature. In most cases they involve muscle contraction force calculations that are statically indeterminate, and hence use optimization techniques to make those calculations. We present a linear programming optimization technique that solves a two-objective problem with two sequential linear programs. We use the technique here to minimize muscle intensity and joint compression force, since those are commonly used objectives. The two linear program model has the advantages of low computation cost, ready implementation on a micro-computer, and stable solutions. We show how to solve the model analytically in simple cases. We also discuss the use of the dual problem of linear programming to gain understanding of the solution it provides. PMID- 3339030 TI - Gallstones in a Danish population: familial occurrence and social factors. PMID- 3339031 TI - Sociodemographic characteristics and intentions for further births in France. PMID- 3339032 TI - Union instability and fertility in three Caribbean societies. PMID- 3339033 TI - Infant and child mortality in Bangladesh. PMID- 3339034 TI - Community-level determinants of infant mortality in Mexico. PMID- 3339035 TI - Infant mortality in Sri Lanka. PMID- 3339036 TI - Maternal factors and infant and child mortality in Bangladesh. PMID- 3339037 TI - The laws of Taharat HaMishpacha: potential effects on fertility. PMID- 3339038 TI - Familial aggregation of consanguineous marriages in Japan. PMID- 3339039 TI - Reconstruction for chronic anterior cruciate instability. A comparison of two methods after six years. AB - Forty-seven patients with disabling instability due to isolated anterior cruciate deficiency are described. None had responded to conservative measures or to attempted correction of internal derangements. Eighteen patients were treated by extra-articular MacIntosh lateral substitution alone, the other 29 were treated by the same procedure combined with carbon-fibre replacement of the anterior cruciate ligament. No statistically significant difference was found between the two groups at six years. A satisfactory outcome was found in 44% of the extra articular group and 55% of the carbon-fibre group at last review; however, the latter group had more complications. There was a marked deterioration in the quality of results between three and six years in both groups. PMID- 3339040 TI - Tibia vara due to focal fibrocartilaginous dysplasia. The natural history. AB - We report five patients with tibia vara due to focal fibrocartilaginous dysplasia of the medial aspect of the proximal tibia. In three patients spontaneous correction occurred, while in one of the remaining two treated by operation, a valgus deformity and neurological complications resulted. Conservative management is therefore recommended. PMID- 3339041 TI - The long-term results of ankle arthrodesis. AB - The results of 62 ankle arthrodeses, mostly performed for osteoarthritis, have been reviewed; of these, 39 were examined clinically and radiographically after an average follow-up period of seven years. Compression arthrodesis was associated with the highest incidence of complications, and an anterior sliding graft gave the most satisfactory results. Very few patients required modification of their footwear; most could walk independently with a slight limp and were able to return to their pre-operative work. However, after operation, the ability to run and to participate in vigorous sporting activities was limited. Complications included wound infection, non-union, and some change in midtarsal mobility, but excellent pain relief was reported by all patients. PMID- 3339042 TI - Spondylothoracic and spondylocostal dysostosis. Hereditary forms of spinal deformity. AB - Two siblings with spondylothoracic dysostosis, and two siblings and three unrelated children with spondylocostal dysostosis are described. Both conditions are inherited and characterised by malformed thoracic and lumbar vertebrae. Spondylothoracic dysostosis produces "crab-like" deformities of the ribs, and is usually fatal during early infancy due to respiratory failure. Spondylocostal dysostosis causes short-trunked dwarfism but does not usually reduce life expectancy. These clinical features are distinct from congenital scoliosis, although all three conditions are associated with a particular group of malformations. PMID- 3339043 TI - The effect of induced hypotension and tissue trauma on renal function in scoliosis surgery. AB - The surgical correction of scoliosis in adolescents involves considerable trauma to bone and muscle which, together with hypotensive anaesthesia, might be expected to compromise renal function. Our recent observation of acute renal failure in two such patients prompted a prospective study of renal function following 52 operations in 43 patients. Despite hypotension, blood loss, muscle damage and evidence of fat embolism, renal function was unaltered in all patients, and there was no impairment of spinal cord function. Careful attention was paid to the maintenance of circulating volume which is essential to protect renal perfusion. PMID- 3339044 TI - Torn acetabular labrum in young patients. Arthroscopic diagnosis and management. AB - Arthroscopy of the hip revealed a torn acetabular labrum in seven young patients. Three of them had had an acute onset of symptoms during sporting activities. On examination all seven patients had pain on passive flexion and medial rotation of the joint. All but one of the tears were located on the posterosuperior portion of the labrum, and, in the acute cases, vascular dilatation around the tear was observed. In these cases, repeated arthroscopy several months later showed that the vascular changes had disappeared, but the tear was still present. The aetiology, diagnosis and treatment of the torn acetabular labrum are discussed. PMID- 3339046 TI - Thenar crush injuries. AB - Crushing of the radial side of the hand results in a wide spectrum of injuries varying from contusion of muscles to total loss. The main problem concerns the function of the thumb. The results of such injuries in 161 hands were reviewed. Those with mild injuries treated conservatively or by debridement alone had good results. When skin flaps were required for wound coverage, the results were still satisfactory. However, when bones and joints were injured, the results were poor. In certain patients opponensplasty through scarred tissue proved to be a good procedure to improve the function of the thumb. PMID- 3339045 TI - The Trillat procedure for recurrent anterior instability of the shoulder. AB - In the Trillat procedure for recurrent anterior instability of the shoulder the coracoid process is osteotomised and tilted downward to act as a bone block, and a screw is used to fix it and the Bankart lesion to the anterior scapular neck. We reviewed 52 cases after a mean follow-up of 69 months. Results in 73% of shoulders were excellent, 10% were good, 7% fair and 10% poor. Dislocation recurred in 4%, but a positive apprehension sign was present in 10 other shoulders. Some degenerative changes were seen in 62% of shoulders, a complication known to be associated with bone-block procedures. The most important reason for loss of lateral rotation was iatrogenic impingement of the coracoid. This frequent and potentially serious complication can also cause posterior subluxation of the humeral head and osteoarthritis. PMID- 3339047 TI - A new prosthesis for the upper limb. AB - We describe the development of a body-powered upper limb prosthesis fitted with a cosmetic functioning hand. The features and advantages of the new design--the PMR (Princess Margaret Rose) prosthesis--are discussed and the clinical results in 15 patients fitted with the prosthesis after above-elbow amputation are described. PMID- 3339049 TI - Compartment syndrome complicating arthroscopic surgery: brief report. PMID- 3339048 TI - The Herbert screw for osteochondral fractures: brief report. PMID- 3339051 TI - Bilateral traumatic anterior dislocation of the hip: brief report. PMID- 3339050 TI - Cervical osteomyelitis after rigid oesophagoscopy: brief report. PMID- 3339052 TI - Sciatic palsy after umbilical catheterisation: brief report. PMID- 3339053 TI - Split-thickness skin excision in severe open fractures. AB - Split-thickness skin excision can be used as a one-stage procedure for the accurate diagnosis of flap viability and the immediate treatment of friction avulsion injuries in severe open fractures. After cleaning the wound, the avulsed flap is temporarily sutured back to its original bed and a split thickness graft is taken from it and meshed to a 1:3 ratio. Surface dermal capillary bleeding then serves as an indicator of viability, clearly displaying a line for the excision of devascularized skin and correlating well with a concomitant fluorescein test. The wounds are re-opened and, after fixation of the fracture, the viable part of the flap is returned to its original bed and the remaining defects are covered with the meshed graft. We have treated 16 patients with extensive degloving injuries in this way, 15 needing only the single surgical procedure. All retained flaps survived, no other donor sites were needed and the split-thickness grafts took with 90% to 100% success. PMID- 3339054 TI - Acid and alkaline phosphatase activity in bone-cyst fluid. AB - The acid and alkaline phosphatase activity in fluid aspirated from solitary bone cysts in six patients was measured, and large increases in the concentration of acid phosphatase were found. In some cases this increase was reflected in venous blood concentrations. The significance of these findings for the pathogenesis and the management of solitary bone cyst is discussed. PMID- 3339055 TI - Stabilisation of the hip in myelomeningocele. Comparison of posterior iliopsoas transfer and varus-rotation osteotomy. AB - Patients with myelomeningocele who had had surgery to stabilise the hip were reviewed; the results of the 106 operations in 88 patients were assessed. In the earlier part of the series there were 55 children who had 64 iliopsoas transfers; later in the series 33 children had 42 varus-rotation osteotomies combined with adductor tenotomy, anterior obturator neurectomy and psoas division. The technical results of both operations were satisfactory: following iliopsoas transfer only 19% of the hips were either dislocated or subluxated; the corresponding figure for the osteotomy was 12%. Thus varus-rotation osteotomy with psoas division, adductor tenotomy and anterior obturator neurectomy was at least as effective in stabilising the hip as iliopsoas transfer. Nevertheless 80% of the latter and 61% of the osteotomy patients relied on wheelchairs for mobility. PMID- 3339056 TI - Injuries of the acetabular triradiate cartilage and sacroiliac joint. AB - Four patients with injuries of the acetabular triradiate cartilage are presented. In three of them premature fusion of the cartilage occurred; two of these developed acetabular deformity and subluxation of the hip. In all patients the sacroiliac joint also was injured; in two, the joint was completely disrupted, leading to fusion and growth disturbance of the ilium. As injury of the triradiate cartilage is easily missed on the initial radiograph, it is advised that all patients with pelvic trauma should be followed clinically and radiographically for at least one year. PMID- 3339058 TI - The Ring uncemented plastic-on-metal total hip replacement. Five-year results. AB - The Ring plastic-on-metal total hip replacement was introduced with the intention of combining the advantages of the cemented low-friction arthroplasty with those of a cementless system. Fourteen hundred and eighty-eight of these procedures have been reviewed. The results of a two to seven-year follow-up, and of a group which has completed at least five years are presented. There was an excellent clinical result in 93% of the whole series, and in 87% of the five-year group. When graded on the Charnley scale there was an average score of 5.86 for pain, 5.96 for function and 5.9 for range of movement, which compares favourably with cemented replacements. The deep infection rate was zero, and the revision rate 1.5% for the whole series. Erosive problems occurred with the smaller acetabular components and the reasons are discussed. The ease and success of exchange have been maintained. PMID- 3339059 TI - Stanmore total hip replacement. A nine- to ten-year follow-up. AB - Between February 1975 and August 1976, 195 total hip replacements using Stanmore components were performed; of these, 146 were in 135 patients who had not had previous hip surgery. At review 52 had died, but none of the others was lost to follow-up. Of the 52, two had had a second operation, one for infection and one for recurrent dislocation. In the remaining 83 patients (92 hips) five revisions were necessary: four for aseptic loosening, and one for stem fracture. The remaining 78 patients had little or no pain and little restriction of activity. After a follow-up period of at least nine years, the survival rate of the prosthesis was 95%. There had been migration of the femoral component in five cases and migration of the acetabular cup in one case, but no wear of the acetabular component could be demonstrated. PMID- 3339057 TI - Acrodysostosis and protrusio acetabuli. An association. AB - Progressive protrusio acetabuli in a patient with acrodysostosis (peripheral dysostosis Type 12) has not, as far as we know, been reported previously. It is recognised that epiphyseal dysplasias may lead to disturbances of acetabular growth, but generally this results in a shallow socket with associated changes in the proximal femoral epiphysis. PMID- 3339060 TI - Long-term results of hip arthroplasty for failure of previous surgery. AB - We report a retrospective review of 127 low friction arthroplasties carried out for the failure of a previous hip operation. After an average follow-up of 10.4 years, 20% of cases required further revision, over half of them for deep infection. We estimated from the radiographic appearances that eventual failure by loosening was probable in 58% on the femoral side and 56% on the acetabular side of the arthroplasties. PMID- 3339061 TI - Intra-articular fluid pressure and pain in osteoarthritis of the hip. AB - We investigated the relationship between the pain experienced by 50 patients with osteoarthritis of the hip and the resting intra-articular pressure of the synovial fluid. We found a significant linear correlation between these factors, greater pain being experienced by patients with higher pressures. In 20 cases we showed that the pressure rises in extension and medial rotation and is least in flexion and mid-abduction. These results help to explain the benefits of rotation osteotomy of the hip and of psoas release. They also help explain the natural resting position of the hip in patients with an acute effusion and the fixed deformities associated with late osteoarthritis of the hip. PMID- 3339062 TI - Revision of total hip replacement for primary osteoarthritis. AB - During the 11-year-period from 1970 to 1980, 799 total hip arthroplasties with metal-on-plastic prostheses were performed for primary osteoarthritis. In all cases high viscosity cement was used, but not under pressure; acetabular cartilage was removed, but the femoral canal was not plugged. The rate of revision and risk factors were evaluated by survivorship analysis. The overall cumulative revision rates were 11%, 14% and 19% after 8, 10, and 14 years respectively. When prophylactic antibiotics were not used, there was a significant risk of revision for infection. The risk of revision for mechanical loosening of both the acetabular and femoral components was significantly increased for men, younger patients, and if a snap-fit prosthesis with a 35 mm head and short wedged stem was used. The survivorship findings were validated by multivariate statistical analysis. PMID- 3339063 TI - Lengthening of the lower limbs in achondroplastic patients. A comparative study of four techniques. AB - We report our experience of lengthening by over 30% a total of 117 lower limbs in achondroplastic patients. We have compared four methods: transverse osteotomy, oblique osteotomy, callotasis of the shaft and chondrodiatasis of the epiphysis. Chrondrodiatasis of the femur and callotasis of the tibia are the techniques which gave fewest complications. PMID- 3339064 TI - Elastic stable intramedullary nailing of femoral shaft fractures in children. AB - We report the use of elastic stable intramedullary nailing (ESIN) in 123 fractures of the femoral shaft in children. Flexible rods are introduced through the distal metaphyseal area, and the aim is to develop bridging callus. Early weight-bearing is possible and is recommended. There was one case of bone infection and no delayed union. Complications were minimal, the most common being minor skin ulceration caused by the ends of the rods. A surprising feature was the low incidence of growth changes, with a mean lengthening of only 1.2 mm after an average follow-up of 22 months. Compared with conservative treatment, ESIN obviates the need for prolonged bed rest and is thus particularly advantageous for treating children. PMID- 3339065 TI - Femoral nerve block for femoral shaft fractures in children: brief report. PMID- 3339067 TI - The Attenborough knee. A four- to ten-year review. AB - The results of 132 Attenborough total knee replacements after a follow-up period of from four to 10 years are presented. Long-term relief of pain and improvement in stability and walking distance were maintained in over two-thirds. The cumulative survivorship with the prosthesis in situ, little or no pain and no radiological loosening was 65% at six years. Problems with wound healing were common, and there was a complication rate of 20% in primary replacements, including a deep-infection rate of 3.5%. Almost 20% of the prostheses needed revision because of aseptic loosening, and there is evidence of radiological and clinical loosening in a further 7.5%. PMID- 3339066 TI - Bone ingrowth into madreporic prostheses. AB - Three madreporic prostheses in two patients were examined to evaluate resorption and formation of the surrounding bone tissue. All three prostheses were firmly fixed and had no clinical or radiographic signs of loosening. Transverse sections were examined by scanning electron microscopy at 40 days, 11 months and 2.5 years after implantation. The findings suggest that adaptive bone remodelling varies along the length of the stem; that bone resorption and formation are related to the time after implant; and that new bone formation (woven bone) can be found very close to the madreporic surface. PMID- 3339068 TI - Orientation of the cruciate ligament in the sagittal plane. A method of predicting its length-change with flexion. AB - We have studied the kinematics of the knee in the sagittal plane, using a four bar linkage as model, and assuming that a "neutral fibre" in each ligament remains isometric throughout flexion. We devised a computer program to calculate the distance separating any pair of points, one on each bone, for various cruciate attachments at various angles of flexion. The parameters for the linkage in four cadaveric knees were obtained by marking the centre of attachment of the cruciate ligaments with tacks and taking lateral radiographs. The movements of the bones were then calculated, in the computer model, for various attachments of "replacement" ligament fibres, the distance between the attachment sites being plotted against the angle of flexion. It was then possible to define zones around the isometric attachment points within which changes in length would be predictable. Our results show that the position of the femoral sites of attachment of both anterior and posterior cruciate replacement was more critical than that of the tibial attachments. PMID- 3339069 TI - Extrathoracic cannulation for urgent cardiopulmonary bypass in cardiac tamponade. Use of the internal jugular vein. AB - Two patients with intra-thoracic cardiovascular catastrophies and cardiac tamponade precluding safe thoracotomy were approached using cannulation of the left internal jugular and femoral veins. Cardiopulmonary bypass could then be established with effective venous drainage before direct approach to the heart and great vessels was attempted. This method produced a satisfactory outcome in both patients. PMID- 3339070 TI - Successful replacement of a fractured Bjork-Shiley aortic valve prosthesis. AB - We report successful surgical intervention following the diagnosis of total aortic valvular incompetence which was caused by the uncommon fracture and disc embolization of a Bjork-Shiley aortic valve prosthesis implanted ten months previously. PMID- 3339071 TI - Spontaneous rupture of the ascending aorta. AB - A case of non-traumatic rupture of the ascending aorta in an hypertensive patient is presented. The clinical findings suggested acute aortic dissection but the typical angiographic features of this entity were not found. PMID- 3339072 TI - Re-implantation of the right coronary artery for ostial stenosis. AB - Stenosis of the coronary arteries is rarely limited to a short ostial lesion. In such cases, consideration should be given to excising the ostial lesion and re implanting the coronary artery. A successful case utilizing this technique is reported. PMID- 3339073 TI - Continuous electroencephalographic monitoring during carotid endarterectomy. AB - Four hundred and twenty-seven carotid endarteriectomies were performed on 377 patients. The electroencephalogram was used as the sole determinant for the use of a carotid shunt in 386 carotid endarterectomies. With clamping of the internal carotid artery, 51 (13%) had electroencephalographic changes. The most common electroencephalographic change (60%) was rapid, ipsilateral attenuation of background activity. In the 30 day follow up period there were 3 deaths (0.7%) and 11 strokes (2.5%). Two patients (0.5%) had intraoperative strokes. The combined morbidity and mortality was 2.8% (12 of 427). Neurologic complications increased significantly with contralateral carotid occlusion. The electroencephalogram correlated well with neurological deficits occurring in surgery, but stump pressures neither correlated with neurological deficits nor electroencephalographic changes. Continuous electroencephalographic monitoring during carotid endarterectomy is an effective method of determining significant cerebral ischemia and the need for a carotid shunt. PMID- 3339074 TI - Lumbar sympathectomy and distal arteriovenous fistula as adjuncts to prevent arterial rethrombosis after thrombectomy: experimental study in dogs. AB - The role of lumbar sympathectomy and distal arteriovenous fistula (AVF) in preventing rethrombosis of femoral arteries with intimal injury and poor run-off was studied in 21 dogs. Femoral artery thrombosis was induced by endothelial lesion in all animals (phase 1) and 24 hours later the arterial flow was restored by thrombectomy. The dogs were then randomly allocated into 3 experimental groups: control, sympathectomy, and AVF (phase 2). Critical stenosis of the popliteal artery was then created by a partially occluding ligature in all animals in order to simulate poor run-off. After 24 hours the femoral arteries were studied for the presence of rethrombosis (phase 3). At the end of phase 2 and during phase 3, femoral pressure and flow, fluorescein circulation time and paw temperature were measured, and arteriography was done. Arterial rethrombosis was significantly prevented in the AVF group (6/7) when compared to the control group (2/7) or the sympathectomy group (1/7). These data suggest an effective action of an adjuvant AVF, but not of sympathectomy in preventing rethrombosis after thrombectomy in arteries with poor run-off. PMID- 3339075 TI - Major arteriovenous fistula complicating aorto-iliac aneurysms. AB - Seven cases of fistula developing between aortic or iliac aneurysms and adjacent major venous trunks are presented. The clinical diagnosis and principles of management of this exceptionally rare complication are discussed in the light of the literature on the subject. PMID- 3339076 TI - Acute limb ischemia due to arterial embolism or thrombosis: influence of limb ischemia versus pre-existing cardiac disease on postoperative mortality rate. AB - Fatal outcome is common after arterial thromboembolectomy. Initial conservative treatment has been suggested to reduce the mortality rate, but the indications for such treatment are poorly defined. This analysis of 201 patients with acute arterial embolism or thrombosis demonstrates that advanced age, recent myocardial infarction, and proximal occlusions are associated with a high mortality rate after arterial thromboembolectomy. Operations performed 13-24 hours after the onset of ischemia, arteriosclerosis in the occluded artery and poor distal backbleeding after completion of thromboembolectomy were also associated with an increased mortality rate, whereas surprisingly the presence of pre-existing cardiac disease, recent myocardial infarction excluded, was not. The present findings suggest that the prognosis quoad vitam after arterial thromboembolectomy is influenced by limb ischemia itself and possibly also by the revascularization procedure. It is suggested that the severity of limb ischemia and an assessment of cardiac function should determine the initial treatment: conservative treatment, or early attempts at revascularization. PMID- 3339077 TI - Treatment of lymphorrhea with exposed or infected vascular prosthetic grafts in the groin using sartorius myoplasty. AB - Thirteen myoplasties using the sartorius muscle were performed on 12 patients from 1980 to 1985 for "healing problems" in the groin with subjacent synthetic grafts. Persistant aseptic lymphorrhea was the indication for 4 patients. In 3 other cases, bacterial cultures from the wound were positive. In 2 other patients there was clinical evidence of sepsis with purulent discharge from the wound and an exposed graft. In 3 cases myoplasty was used as a preventive measure after reoperation on patients in poor general condition. Follow-up extends from 3 to 54 months. There was only one recurrence observed at 19 months which was successfully treated by segmental resection of the infected graft and insertion of a new prosthesis through the obturator canal. No recurrence was observed among the other patients as judged by clinical observation and biological tests for inflammation, echotomography, CT scan and indium scintigraphy. The treatment of choice for an infected prosthesis should be removal of the graft and extra anatomic bypass in the majority of cases. However in some situations, excision of the wound and myoplasty using the sartorius muscle may be of some value and needs further evaluation. PMID- 3339078 TI - Chronic perigraft seromas in PTFE grafts. AB - Well known complications of polytetrafluoroethylene (PTFE) grafts include thrombosis, infection, and pseudoaneurysms. Chronic perigraft seromas (CPS) associated with knitted dacron grafts are well described but only sporadic cases have been described in conjunction with PTFE grafts. In order to document the clinical history of PTFE associated CPS, 1674 PTFE grafts placed during the period from December 1982 through December 1984 were evaluated for the presence of CPS. Eight CPS were documented. All CPS developed in the subcutaneous location of the PTFE graft. Biochemical analysis of the seroma fluid and pathological findings implicate the source of the contents as being due to a local defect in the PTFE graft. CPS can make angioaccess difficult, cause discomfort by mass effect, and as in two patients, occlude a graft. Non-operative therapy was ineffective. Removal of the contents and as much of the pseudocapsule as possible was effective with only a single small recurrence. PMID- 3339079 TI - Massive atheromatous emboli to both kidneys: a fatal complication following aortic surgery. AB - A patient with severe and diffuse ulcerative atherosclerotic arterial disease developed acute renal failure and anuria during insertion of an aortobifemoral graft. Postoperative septicemia, with Pseudomonas aeruginosa and Streptococcus fecalis, led to a deterioration in his condition and death. At autopsy the Dacron bifurcation graft showed no sign of infection, but massive atheromatous emboli of recent origin were found in both kidneys. We suggest using an extra-anatomic approach in reconstructive surgery for occlusive disease of the abdominal aorta in patients with ulcerative atheroma. PMID- 3339080 TI - Vertebral aneurysm of the neck. AB - We recently encountered a case of a huge vertebral aneurysm involving the entire right neck, extending from the clavicle to the mandibular area. The patient had undergone laminectomy of the cervical spine at age 45 for neuritis or spinal caries. This operative procedure apparently caused a small vertebral laceration and produced the giant aneurysm. The aneurysm was resected under hypothermia in order to protect the brain. One vertebral artery was ligated, but cerebral damage did not occur. Only a few cases of huge aneurysms extending from the clavicle to the mandible have been reported in the literature. PMID- 3339081 TI - Arteriovenous malformation of the gluteal artery during pregnancy. AB - We describe a case of a congenital arteriovenous fistula of the gluteal artery, a posterior branch of the left iliac artery, developing during pregnancy without postpartum regression after delivery. Surgical excision without preoperative embolisation was made possible by prior ligation of the gluteal artery. PMID- 3339082 TI - Does non-invasive carotid testing influence the selection of patients for carotid surgery? AB - To help define the role of non-invasive carotid testing, all patients undergoing carotid endarterectomy between January 1/1978 and December 31/1983 were reviewed. In late 1979, non-invasive carotid tests became available. No significant changes in the indications for carotid endarterectomy occurred in this interval, and all carotid patients were investigated with arteriography prior to operation. In this setting, we investigated the role, if any, of the carotid laboratory. Within two years of introduction, 1200 carotid tests were performed annually, a level which remained stable. It was found that the percentage of patients with significant lesions at arteriography increased, and the proportion of patients progressing to surgery after arteriography went up by 50%. Remarkably, the number of arteriograms did not increase in this interval. The present ratio of non-invasive studies to angiograms is 12:1, but when this ratio was only 4.6:1 in 1980, the increased yield of surgery following angiography was already noted. These results indicate that the non-invasive tests increase the accuracy of clinical diagnosis, place relatively fewer patients at risk from angiography, and are readily accepted and used by clinical staff even when angiography is used to evaluate all possible operative candidates. The results suggest that these benefits can be realized when non-invasive tests are ordered when necessary after careful clinical evaluation, and that their use as a screening measure in all patients with possible cerebrovascular disease may not be necessary. PMID- 3339083 TI - Central venous blood temperature for rate control of physiological pacemakers. AB - In 17 pacemaker patients and 14 volunteers we studied the behaviour of central venous blood temperature and heart rate under different kinds of exercise. Data were recorded by means of 5F catheter placed at the right ventricle. Temperature was measured with a thermistor incorporated in the lead. We found the increase in central venous blood temperature to be dependent on the individual exercise capacity and work load performed. The maximum temperature increase seen was 1.7 degrees Celsius. Subjects with lower physical fitness showed a more pronounced increase in temperature and heart rate compared to more physically fit subjects at the same work load. Due to its close relationship to metabolic and circulatory parameters, central venous blood temperature represents an appropriate signal to control the rate of physiological pacemaker systems. A special algorithm also using the initial dip for rate control has been incorporated into a pacemaker system, that is currently under clinical investigation (Intermedics NOVA MR). PMID- 3339084 TI - Surgery for congenital abnormalities of the mitral valve at the Hospital for Sick Children, London from 1969-1983. AB - The surgical management of congenital mitral valve (MV) anomalies remains controversial and complex. Valve repair has been said to be preferable to valve replacement. To assess the validity of this suggestion we have reviewed our experience of these procedures at The Hospital for Sick Children, Great Ormond Street, London from 1969-1983. In that time 48 patients have undergone surgery; in 23 repair was practicable (Group A) and in 25 replacement of the MV was required (Group B). Group A patients were slightly older than group B patients (5.9 +/- 1.0 years (SEM) vs 3.6 +/- 0.5 years). Bjork Shiley valves were the predominant prosthesis used. Overall mortality was 33%, with 17% in Group A and 48% in Group B. Hospital mortality was 4.5% in Group A and 28% in Group B. Actuarial survival for Group A was 90% at 1 year, and 75% at 2 and 5 years; for Group B it was 52% at 1 and 2 years and 42% at 5 years. Mortality was significantly higher in those aged less than 5 years. Four patients in Group A have required re-operation, in 3 valve replacement was required; 2 of these died in hospital. One patient in Group B has required reoperation for valve-related thromboembolism. Three patients are awaiting replacement of calcified bioprostheses. These data support the concept that repair of MV should be performed where possible. The severity of the anomalies was greater in Group B and a rethink as to whether valve replacement is the best option for severe mitral stenosis in those aged less than 5 years seems indicated, in view of the very high mortality. PMID- 3339085 TI - Steps in the assembly of replication-competent nuclei in a cell-free system from Xenopus eggs. AB - We have studied the pathway of nuclear assembly from demembranated sperm chromatin by fractionating a cell-free system from Xenopus eggs (Lohka, M. J., and Y. Masui. 1983. Science (Wash. DC). 220:719-721). Both the soluble fraction and a washed vesicular fraction are required for formation of normal nuclei that initiate replication in vitro. The soluble fraction alone decondenses chromatin and the vesicular fraction alone surrounds chromatin with membranes. Both fractions are required for formation of nuclear pore complexes. Recombining these two fractions recovers approximately 100% of the nuclear assembly and DNA replication activities. Restricting the proportion of the vesicular fraction slows acquisition of the nuclear membrane and allows observation of immature nuclear pores ("prepores"). These form as arrays around and within the chromatin mass before membranes form. Subsequently membrane vesicles bind to these prepores, linking them by a single membrane throughout the chromatin mass. At the periphery this single membrane is surrounded by an outer membrane. In mature nuclei all membranes are at the periphery, the two membranes are linked by pores, and no prepores are seen. Nuclear assembly and replication are inhibited by preincubating the chromatin with the vesicular fraction. However nuclear assembly is accelerated by preincubating the condensed chromatin with the soluble fraction. This also decreases the lag before DNA replication. Initiation of DNA replication is only observed after normal nuclei have fully reassembled, increasing the evidence that replication depends on nuclear structure. The pathway of nuclear assembly and its relationship to DNA replication are discussed. PMID- 3339086 TI - The polarity and stability of microtubule capture by the kinetochore. AB - We have studied the capture of microtubules by isolated metaphase chromosomes, using microtubules stabilized with taxol and marked with biotin tubulin to distinguish their plus and minus ends. The capture reaction is reversible at both the plus and minus ends. The on rate of capture is the same for both polarities but the dissociation rate from the kinetochore is seven times slower with microtubules captured at their plus ends than those captured at their minus ends. At steady state this disparity in off rates leads to the gradual replacement of microtubules captured at their minus ends with those captured at their plus ends. These results suggest that the kinetochore makes a lateral attachment near the end of the microtubule in the initial capture reaction and shows a structural specificity that may be important in proper bipolar attachment of the chromosome to the spindle. PMID- 3339087 TI - A nerve growth factor-regulated messenger RNA encodes a new intermediate filament protein. AB - Differential screening of a cDNA library from the PC12 rat pheochromocytoma cell line previously revealed a clone, clone 73, whose corresponding mRNA is induced by nerve growth factor (NGF). Induction parallels NGF-stimulated PC12 differentiation from a chromaffinlike phenotype to a sympathetic neuronlike phenotype. We report that DNA sequence analysis reveals that clone 73 mRNA encodes an intermediate filament (IF) protein whose predicted amino acid sequence is distinct from the known sequences of other members of the IF protein family. The sequence has highest homology with desmin and vimentin and includes the highly conserved central alpha-helical rod domain with the characteristic heptad repeat of hydrophobic residues, but has lower homology in the amino-terminal head and carboxyl-terminal tail domains. The head domain contains a large number of serine residues which are potential phosphorylation sites. The expression of clone 73 in vivo in the nervous system of the adult rat was investigated by in situ hybridization of clone 73 probes to tissue sections. The mRNA is expressed at high levels in ganglia of the peripheral nervous system, including the superior cervical ganglion (sympathetic), ciliary ganglion (parasympathetic), and dorsal root ganglion (sensory). In the central nervous system, motor nuclei of cranial nerves III, IV, V, VI, VII, X, and XII as well as ventral horn motor neurons and a restricted set of other central nervous system nuclei express the clone 73 mRNA. Tissues apart from those of the nervous system did not in general express the mRNA, with only very low levels detected in adrenal gland. We discuss the implications of these results for the mechanism of NGF-induced PC12 cell differentiation, the pathways of neuronal development in vivo, and the possible function of the clone 73 IF protein and its relationship to other IF proteins. PMID- 3339088 TI - Developmentally regulated expression of a Balbiani ring 1 gene for a 180-kD secretory polypeptide in Chironomus tentans salivary glands before larval/pupal ecdysis. AB - The expression of a Balbiani ring 1 gene that codes for a salivary gland-specific 180-kD secretory polypeptide (sp180) is regulated developmentally. Immunoblots of salivary gland protein incubated with an affinity-purified nonapeptide-reactive antibody demonstrated that the salivary gland content of sp180 increases as much as 10-fold between stages 8 and 10 of the fourth larval instar. Hybridization of RNA dot-blots with an oligonucleotide probe indicated that the observed increase in sp180 was preceded by a parallel 20-fold increase in the steady state level of its mRNA beginning between stages 7 and 8. In vitro nuclear transcription experiments demonstrated that there was a 10-fold acceleration in the rate of sp180 gene transcription between stages 6 and 10. The limited period of expression of the sp180 gene contrasted dramatically with the expression of Balbiani ring genes BR1, BR2 alpha, BR2 beta, and BR6, which code for the sp-I family of fibrous secretory polypeptides. The appearance of sp180 in secretion coincided with microscopically visible changes in the bundling of these fibrous polypeptides. At the same time, we noticed changes in the appearance and consistency of feeding tubes that larvae construct with this secretion. These results lead us to propose that sp180 may modify the structure or utilization of fibrous secretory polypeptides specifically for the assembly of pupation tubes necessary for larval/pupal ecdysis. PMID- 3339089 TI - Purification and biosynthesis of a derepressible periplasmic arylsulfatase from Chlamydomonas reinhardtii. AB - The unicellular green alga Chlamydomonas reinhardtii responds to sulfate deprivation by producing an arylsulfatase (Lien, T., and O. Schreiner. 1975. Biochim. Biophys. Acta. 384:168-179; Schreiner, O., 1975. Biochim. Biophys. Acta. 384:180-193) and by developing the capacity to transport sulfate more rapidly (our unpublished data). The arylsulfatase activity, detectable 3 h after the transfer of the cells to low sulfate medium (less than or equal to 10 microM sulfate), is a periplasmic protein released into the culture medium by cw15, a cell wall-less mutant of C. reinhardtii. We have purified the derepressible arylsulfatase to homogeneity and have raised monospecific antibodies to it. The protein monomer (67.6 kD) associates into a dimer, and the enzyme activity shows an alkaline pH optimum and a Km of 0.3 mM for p-nitrophenylsulfate. Studies focused on arylsulfatase biosynthesis demonstrate that it is glycosylated and synthesized as a higher molecular mass precursor. The mature protein contains complex N-linked oligosaccharides and the primary translation product has an apparent molecular mass approximately 5 kD larger than the deglycosylated monomer. Since translatable RNA encoding the arylsulfatase can only be detected in cells after sulfate starvation, it is likely that accumulation of the enzyme is regulated at the level of transcription, although posttranscriptional processes may also be involved. PMID- 3339091 TI - Intracellular transport of a variant surface glycoprotein in Trypanosoma brucei. AB - Trypanosome variant surface glycoproteins (VSGs) have a novel glycan phosphatidylinositol membrane anchor, which is cleavable by a phosphatidylinositol-specific phospholipase C. A similar structure serves to anchor some membrane proteins in mammalian cells. Using kinetic and ultrastructural approaches, we have addressed the question of whether this structure directs the protein to the cell surface by a different pathway from the classical one described in other cell types for plasma membrane and secreted glycoproteins. By immunogold labeling on thin cryosections we were able to show that, intracellularly, VSG is associated with the rough endoplasmic reticulum, all Golgi cisternae, and tubulovesicular elements and flattened cisternae, which form a network in the area adjacent to the trans side of the Golgi apparatus. Our data suggest that, although the glycan-phosphatidylinositol anchor is added in the endoplasmic reticulum, VSG is nevertheless subsequently transported along the classical intracellular route for glycoproteins, and is delivered to the flagellar pocket, where it is integrated into the surface coat. Treatment of trypanosomes with 1 microM monensin had no effect on VSG transport, although dilation of the trans-Golgi stacks and lysosomes occurred immediately. Incubation of trypanosomes at 20 degrees C, a treatment that arrests intracellular transport from the trans-Golgi region to the cell surface in mammalian cells, caused the accumulation of VSG molecules in structures of the trans-Golgi network, and retarded the incorporation of newly synthesized VSG into the surface coat. PMID- 3339090 TI - Structure of LEP100, a glycoprotein that shuttles between lysosomes and the plasma membrane, deduced from the nucleotide sequence of the encoding cDNA. AB - LEP100, a membrane glycoprotein that has the unique property of shuttling from lysosomes to endosomes to plasma membrane and back, was purified from chicken brain. Its NH2-terminal amino acid sequence was determined, and an oligonucleotide encoding part of this sequence was used to clone the encoding cDNA. The deduced amino acid sequence consists of 414 residues of which the NH2 terminal 18 constitute a signal peptide. The sequence includes 17 sites for N glycosylation in the NH2-terminal 75% of the polypeptide chain followed by a region lacking N-linked oligosaccharides, a single possible membrane-spanning segment, and a cytoplasmic domain of 11 residues, including three potential phosphorylation sites. Eight cysteine residues are spaced in a regular pattern through the lumenal (extracellular) domain, while a 32-residue sequence rich in proline, serine, and threonine occurs at its midpoint. Expression of the cDNA in mouse L cells resulted in targeting of LEP100 primarily to the mouse lysosomes. PMID- 3339093 TI - A stochastic model for leukocyte random motility and chemotaxis based on receptor binding fluctuations. AB - Two central features of polymorphonuclear leukocyte chemosensory movement behavior demand fundamental theoretical understanding. In uniform concentrations of chemoattractant, these cells exhibit a persistent random walk, with a characteristic "persistence time" between significant changes in direction. In chemoattractant concentration gradients, they demonstrate a biased random walk, with an "orientation bias" characterizing the fraction of cells moving up the gradient. A coherent picture of cell movement responses to chemoattractant requires that both the persistence time and the orientation bias be explained within a unifying framework. In this paper, we offer the possibility that "noise" in the cellular signal perception/response mechanism can simultaneously account for these two key phenomena. In particular, we develop a stochastic mathematical model for cell locomotion based on kinetic fluctuations in chemoattractant/receptor binding. This model can simulate cell paths similar to those observed experimentally, under conditions of uniform chemoattractant concentrations as well as chemoattractant concentration gradients. Furthermore, this model can quantitatively predict both cell persistence time and dependence of orientation bias on gradient size. Thus, the concept of signal "noise" can quantitatively unify the major characteristics of leukocyte random motility and chemotaxis. The same level of noise large enough to account for the observed frequency of turning in uniform environments is simultaneously small enough to allow for the observed degree of directional bias in gradients. PMID- 3339092 TI - Light-regulated translation of chloroplast proteins. I. Transcripts of psaA-psaB, psbA, and rbcL are associated with polysomes in dark-grown and illuminated barley seedlings. AB - We have previously observed (Klein, R. R., and J. E. Mullet, 1986, J. Biol. Chem. 261:11138-11145) that translation of two 65-70-kD chlorophyll a-apoproteins of Photosystem I (gene products of psaA and psaB) and a 32-kD quinone-binding protein of Photosystem II (gene product of psbA) was not detected in plastids of dark-grown barley seedlings even though transcripts for these proteins were present. In the present study it was found that nearly all of the psaA-psaB transcripts in plastids of dark-grown plants were associated with membrane-bound polysomes. Membrane-associated polysomes from plastids of dark-grown plants synthesized the 65-70-kD chlorophyll a-apoproteins at low levels when added to a homologous in vitro translation extract capable of translation elongation. However, when etioplast membranes were disrupted with detergent, in vitro synthesis of the 65-70-kD chlorophyll a-apoproteins increased to levels observed with polysomes of plastids from illuminated plants. These results suggest that synthesis of the chlorophyll a-apoproteins of Photosystem I is arrested on membrane-bound polysomes at the level of polypeptide chain elongation. In addition to the selective activation of chlorophyll a-apoprotein translation, illumination also caused an increase in chloroplast polysomes (membrane associated and stromal) and induced a recruitment of psbA and rbcL transcripts into chloroplast polysomes. These results indicate that in conjunction with the selective activation of chlorophyll a-apoprotein elongation, illumination also caused a general stimulation of chloroplast translation initiation. PMID- 3339094 TI - Analysis of lateral redistribution of a plasma membrane glycoprotein-monoclonal antibody complex [corrected]. AB - The lateral redistribution of a major murine glycoprotein, GP80, was studied on locomoting fibroblasts, using rhodamine-conjugated mAbs and ultralow light level digitized fluorescence microscopy. Confirming an earlier study (Jacobson, K., D. O'Dell, B. Holifield, T.L. Murphy, and J. T. August. 1984. J. Cell Biol. 99:1613 1623), the distribution of GP80 was coupled with cell locomotion; motile cells exhibited a gradated distribution of the GP80-mAb complex over the cell surface, increasing from the front to the rear, whereas stationary cells exhibited a nearly uniform GP80 distribution. By monitoring locomoting single cells, we found the gradated fluorescence distribution to be maintained as an approximate steady state. Newly extended leading edges were almost devoid of the fluorescence labeling. This was strikingly demonstrated in prechilled cells in which the extension of fluorescence-free leading edges caused a pronounced boundary between fluorescent and nonfluorescent zones. Subsequently this boundary eroded gradually in a manner consistent with diffusional relaxation. Evidence indicated that the GP80 redistribution was primarily caused by the lateral motion of GP80 in the plasma membrane and not via intracellular membrane traffic. Two cell locomotion models which, in principle, could account for the GP80 redistribution were tested: the retrograde lipid flow (RLF) model (Bretscher, M. S., 1984. Science (Wash. DC). 224:681-686) and an alternative hypothesis, the retraction-induced spreading (RIS) model. The predictions of these models were stimulated by computer and compared with experiment to assess which model was more appropriate. Whereas both models predicted steady-state gradients similar to the experimental result, only the RIS model predicted the lack of retrograde movement of the fluorescent boundary. PMID- 3339095 TI - Actin filaments, stereocilia, and hair cells of the bird cochlea. V. How the staircase pattern of stereociliary lengths is generated. AB - The stereocilia on each hair cell are arranged into rows of ascending height, resulting in what we refer to as a "staircase-like" profile. At the proximal end of the cochlea the length of the tallest row of stereocilia in the staircase is 1.5 micron, with the shortest row only 0.3 micron. As one proceeds towards the distal end of the cochlea the length of the stereocilia progressively increases so that at the extreme distal end the length of the tallest row of the staircase is 5.5 micron and the shortest row is 2 micron. During development hair cells form their staircases in four phases of growth separated from each other by developmental time. First, stereocilia sprout from the apical surfaces of the hair cells (8-10-d embryos). Second (10-12-d embryos), what will be the longest row of the staircase begins to elongate. As the embryo gets older successive rows of stereocilia initiate elongation. Thus the staircase is set up by the sequential initiation of elongation of stereociliary rows located at increased distances from the row that began elongation. Third (12-17-d embryos), all the stereocilia in the newly formed staircase elongate until those located on the first step of the staircase have reached the prescribed length. In the final phase (17-d embryos to hatchlings) there is a progressive cessation of elongation beginning with the shortest step and followed by taller and taller rows with the tallest step stopping last. Thus, to obtain a pattern of stereocilia in rows of increasing height what transpires are progressive go signals followed by a period when all the stereocilia grow and ending with progressive stop signals. We discuss how such a sequence could be controlled. PMID- 3339097 TI - Changes in the expression of collagen genes show two stages in chondrocyte differentiation in vitro. AB - This report deals with the quantitation of both mRNA and transcription activity of type I collagen gene and of three cartilage-specific collagens (types II, IX, and X) during in vitro differentiation of chick chondrocytes. Differentiation was obtained by transferal to suspension culture of dedifferentiated cells passaged for 3 wk as adherent cells. The type I collagen mRNA, highly represented in the dedifferentiated cells, rapidly decreased during chondrocyte differentiation. On the contrary, types II and IX collagen mRNAs sharply increased within the first week of suspension culture, peaked in the second week, and thereafter began to decrease. This decrease was particularly significant for type IX collagen mRNA. The level of type X collagen mRNA progressively increased during the course of the culture, reached its maximal value after 3-4 wk, and decreased only at a later stage of cell differentiation. As determined by in vitro run-off transcription assays, all these changes in collagen mRNA levels could be attributed to parallel modifications in the relative rate of transcription of the corresponding collagen genes. We suggest that chicken chondrocyte differentiation proceeds through at least two different steps: (a) first, transition from a stage characterized by a high level of type I collagen mRNA to a stage characterized by predominance of types II and IX collagen mRNAs; (b) later, transition to a stage characterized by the highest level of type X collagen mRNA. PMID- 3339096 TI - Developmental expression of 2ar (osteopontin) and SPARC (osteonectin) RNA as revealed by in situ hybridization. AB - 2ar has been identified as a gene inducible by tumor promoters and growth factors in a variety of cultured mouse cell lines (Smith, J. H., and D. T. Denhardt. 1987. J. Cell. Biochem. 34:13-22). Sequence analysis shows that it codes for mouse osteopontin, an RGDS-containing, phosphorylated, sialic acid-rich Ca++ binding protein originally isolated from bone (Oldberg, A., A. Franzen, and D. Heinegard. 1986. Proc. Natl. Acad. Sci. USA. 83:8819-8823; Prince, C. W., T. Oosawa, W. T. Butler, M. Tomana, A. S. Brown, and R. E. Schrohenloer. 1987. J. Biol. Chem. 262:2900-3907.). In this paper we use Northern blot analysis and in situ hybridization to localize expression of 2ar during mouse embryogenesis. 2ar RNA is first detected in developing limb bones and calvaria at 14.5 d p.c., in a population of cells distinct from those expressing SPARC (osteonectin). High levels of 2ar expression are also seen in the bone marrow-derived granulated metrial gland cells of the deciduum and placenta, and in a number of epithelial tissues, including embryonic and postnatal kidney tubules, uterine epithelium and sensory epithelium of the embryonic ear. The temporal and spatial pattern of 2ar expression seen in vivo suggests that the protein plays a wider role than previously realized, in processes which are not confined to bone development. PMID- 3339100 TI - Autoradiographic determination of cerebral glucose content, blood flow, and glucose utilization in focal ischemia of the rat brain: influence of the plasma glucose concentration. AB - Focal cerebral ischemia was produced by occlusion of the middle cerebral artery in rats. Cerebral blood flow measured with [14C]iodoantipyrine was severely reduced in the lateral portion of neostriatum. This area of dense ischemia was sharply demarcated against the surroundings. The adjacent cortex was perfused at one-third of normal, whereas blood flow in the medial neostriatum was only slightly reduced. This pattern of perfusion was independent of the plasma glucose concentration of the animal. In contrast, the glucose utilization calculated from the 2-[3H]deoxyglucose accumulation depended on the plasma glucose concentration. Enhanced glucose utilization was evident in the border areas surrounding the ischemic focus in normoglycemic animals. Neither acutely nor chronically diabetic animals had such an increase of metabolism in the borderzone. Moderately hyperglycemic rats had a narrow rim of enhanced glucose utilization immediately surrounding the ischemic core, whereas animals with plasma glucose values above 22 mmol/L had no such rim. In mild hypoglycemia (2-4 mmol/L), the glucose utilization was slightly enhanced in the border areas, but during severe hypoglycemia (less than 2.5 mmol/L), the glucose utilization declined gradually toward the ischemic core. Glucose content, and thereby the lumped constant (measured by 3-0-[14C]methylglucose) showed little regional variation, except in the ischemic core. These findings indicate that blood flow alterations after occlusion of the middle cerebral artery in rats are not influenced by the plasma glucose utilizations. In contrast, glucose utilization depends on a combination of plasma glucose concentration and blood flow instead of blood flow per se. PMID- 3339098 TI - Regulation of acetylcholine receptor transcript expression during development in Xenopus laevis. AB - The level of transcripts encoding the skeletal muscle acetylcholine receptor (AChR) was determined during embryonic development in Xenopus laevis. cDNAs encoding the alpha, gamma, and delta subunits of the Xenopus AChR were isolated from Xenopus embryo cDNA libraries using Torpedo AChR cDNAs as probes. The Xenopus AChR cDNAs have greater than 60% amino acid sequence homology to their Torpedo homologues and hybridize to transcripts that are restricted to the somites of developing embryos. Northern blot analysis demonstrates that a 2.3-kb transcript hybridizes to the alpha subunit cDNA, a 2.4-kb transcript hybridizes to the gamma subunit cDNA, and that two transcripts, of 1.9 and 2.5 kb, hybridize to the delta subunit cDNA. RNase protection assays demonstrate that transcripts encoding alpha, gamma, and delta subunits are coordinately expressed at late gastrula and that the amount of each transcript increases in parallel with muscle specific actin mRNA during the ensuing 12 h. After the onset of muscle activity the level of actin mRNA per somite remains relatively constant, whereas the level of alpha subunit and delta subunit transcripts decrease fourfold per somite and the level of gamma subunit transcript decreases greater than 50-fold per somite. The decrease in amount of AChR transcripts per somite, however, occurs when embryos are paralyzed with local anaesthetic during their development. These results demonstrate that AChR transcripts in Xenopus are initially expressed coordinately, but that gamma subunit transcript levels are regulated differently than alpha and delta at later stages. Moreover, these results demonstrate that AChR transcript levels in Xenopus myotomal muscle cells are not responsive to electrical activity and suggest that AChR transcript levels are influenced by other regulatory controls. PMID- 3339102 TI - Measurement of local cerebral blood flow with [14C]iodoantipyrine in the mouse. AB - Local cerebral blood flow was measured in the mouse by means of the [14C]iodoantipyrine method. This method has been previously used in the monkey, dog, cat, and rat, but its application to small mammals such as the mouse requires special attention to potential sources of error. The small size of the mouse brain requires special attention to the rapid removal and freezing of the brain to minimize effects of postmortem diffusion of tracer in the tissue. Because of the relatively low diameter/length ratios of the catheters needed for arterial sampling in small animals, substantial errors can occur in the determination of the time course of the [14C]iodoantipyrine concentration in the arterial blood unless corrections for lag time and dead space washout in the catheter are properly applied. Local cerebral blood flow was measured in seven awake mice with appropriate care to minimize these sources of error. The values were found to vary from 48 ml/100 g/min in the corpus callosum to 198 ml/100 g/min in the inferior colliculus. The results demonstrate that the [14C]iodoantipyrine method can be used to measure local cerebral blood flow in the mouse and that the values in that species are, in general, somewhat higher than those in the rat. PMID- 3339099 TI - Free radical reaction and biological defense mechanism in the pathogenesis of prolonged vasospasm in experimental subarachnoid hemorrhage. AB - The relationship between free radical reactions and the defense mechanisms against them was investigated in the pathogenesis of prolonged vasospasm following experimental subarachnoid hemorrhage (SAH) in dogs. The concentration of lipid peroxides in the cerebro spinal fluid (CSF) increased markedly up to the eighth day following SAH; the concentrations also rose in the arterial wall (p less than 0.01) and the gray matter of the temporal lobe where the subarachnoid blood clots were (p less than 0.01). On the other hand, the activity of superoxide dismutase (SOD) decreased significantly up to the eighth day after SAH (p less than 0.01), and there was a gradual increase of glutathione peroxidase (GSH-px) in the CSF. In the arterial wall, there was a slight decrease in the activity of SOD, a significant decrease in the activity of GSH-px (p less than 0.01), and also a significant decrease in the concentration of glutathione (p less than 0.01) up to the eighth day following SAH. In conclusion, lipid peroxidation with insufficient biological defense mechanisms against it in the arterial wall, concomitant with that in the CSF, might take part in the genesis of prolonged vasospasm following SAH. PMID- 3339101 TI - Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat. AB - Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer--14C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions. PMID- 3339104 TI - Field of view for gamma ray detectors and extended radiation sources. PMID- 3339103 TI - Extracellular lactic acid as an indicator of brain metabolism: continuous on-line measurement in conscious, freely moving rats with intrastriatal dialysis. AB - Lactic acid was measured continuously in the dialysis perfusate emerging from the striatum of conscious, freely moving rats. The continuous measurement utilized a specific enzymatic/fluorometric detector that provided temporal information about the changes in the concentration of lactate in extracellular fluid (ECF). The level of lactate in extracellular fluid was found to be directly linked to local cellular metabolism. Inhibition of glycolysis with 2-deoxyglucose decreased the ECF level of lactate, whereas increased lactate production was observed after uncoupling mitochondrial electron transport with 2,4-dinitrophenol. A transient increase in the extracellular level of lactate was found after neuronal stimulation (e.g., electroconvulsive shock or local administration of kainic acid). The response to electroconvulsive shock could be attenuated by inhibiting the electrical activity of neurons with tetrodotoxin. Thus, this system is capable of providing novel information about transient changes in the extracellular concentration of lactic acid in real time, and these changes can be related to changes in metabolism and neuronal activity. PMID- 3339105 TI - High energy phosphate metabolism in experimental permanent focal cerebral ischemia: an in vivo 31P magnetic resonance spectroscopy study. AB - Relative levels of phosphate metabolites in the brain were examined in vivo by 31P magnetic resonance spectroscopy (MRS) in 50 Sprague-Dawley rats before, during, and after induction of focal permanent cerebral ischemia. After acquisition of baseline spectra, rats were subjected to injury within the core of the MR spectrometer, and 31P spectra were collected for 60 min after injury: in 7 rats, permanent, acute focal cerebral ischemia was induced (ischemia group); in 6 rats, mild hypoxia (FiO2 14%) was induced at the time of the ischemic insult and was maintained for 20 min (ischemia-hypoxia group); in 6 rats, mild hypoxia (FiO2 14%) only was induced for 20 min (hypoxia group). Control studies were performed in 25 rats. Cerebral intracellular pH, calculated from the chemical shift of inorganic phosphate (Pi), decreased immediately after injury in the ischemia and ischemia-hypoxia groups. The first 31P spectrum obtained after injury was characterized by an increase in Pi and a decrease in phosphocreatine (PCr) in the ischemia and ischemia-hypoxia groups; these changes in spectra were significantly greater in the ischemia-hypoxia group. No significant changes in adenosine triphosphate (ATP) were found in either group. Within 60 min of occlusion, 31P spectra returned toward baseline spectra in both ischemia-hypoxia and ischemia groups. No significant changes were seen in spectra of rats subjected to hypoxia alone. These results confirm that 31P MRS is a sensitive measure of early changes of high energy metabolites in focal cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339106 TI - Adenosine receptors and the nucleoside transporter in human brain vasculature. AB - Evidence suggests that adenosine modulates neuronal and cerebral vascular functions by interacting with specific receptors on brain cells and blood vessels. Adenosine and other nucleosides are also transported across the blood brain barrier via a saturable, carrier-mediated mechanism. Using direct ligand binding methods, we studied the two adenosine receptor subtypes, A1 and A2 and the nucleoside transporter moiety in human brain microvessels, pial vessels, choroid plexus, and cerebral cortex membranes. The following specific tritiated ligands were used: cyclohexyladenosine (CHA) for A1 receptors; 5'-N ethylcarboxamide adenosine (NECA) for A2 receptors; nitrobenzylthioinosine (NBMPR) and dipyridamole (DPY) for nucleoside transporters. We find that cerebral microvessels, pial vessels, and choroid plexus have few, if any, A1 receptors, in contradistinction to cerebral membranes, which have a 10-20-fold higher density of A1 receptor sites. Specific high-affinity NECA binding to A2 receptors in cerebral microvessels, pial vessels, and choroid plexus was saturable and was equivalent to that of cerebral cortical membranes. The Bmax and Kd of the high affinity NECA binding to vessel preparations were approximately 1.3 pmol/mg protein and approximately 250 nM, respectively, which is similar to our previous findings in the rat and pig. NBMPR and DPY binding were also saturable and were consistent with a single class of high-affinity binding sites. The density of nucleoside transporters was approximately four-fold higher in cerebral microvessels than in cerebral cortex, pial vessels, and choroid plexus. These results suggest that human cerebral microvessels have A2, but not A1, receptors and are particularly enriched with the adenosine transporter moiety. PMID- 3339107 TI - Changes in vascular and metabolic reactivity as indices of ischaemia in the penumbra. AB - The reactivities of cerebral cortical blood flow (hydrogen clearance) and of compensated NADH fluorescence to local cortical electrical stimulation were examined on the marginal gyrus before and after transorbital occlusion of the middle cerebral artery in cats. Prestimulus cerebral blood flow (CBF) was 38.2 +/ 12.9 (SD) ml 100 g-1 min-1 and fell to 19.8 +/- 11.1 following occlusion (p less than 0.02). Peak hydrogen clearance rate (percent increase above prestimulus clearance) was 81.6 +/- 53.6 and fell to 19.9 +/- 29.8 after middle cerebral artery occlusion (p less than 0.01). Steady-state NADH fluorescence rose from 33.5 +/- 10.7 to 40.5 +/- 17.6% full-scale deflection following MCAO (p less than 0.01). Latency from stimulus to maximal fluorescence depression in response to cortical stimulation increased from 12.2 +/- 8.2 to 22.1 +/- 11.9 s (p less than 0.01). Hyperaemic responses at anteromedial sites on the marginal gyrus significantly exceeded those at posterolateral sites. The results are interpreted as indicating early ischaemic metabolic change; however, the presence of residual vasodilator responses to stimulation suggests that flow reduction and early ischaemic change in the territory studied are not simply due to inadequate collateral input, but may also reflect deafferentation or functional suppression. The possible significance of diminished vascular reactivity in the penumbra as a cause of increased vulnerability to extracellular release of excitatory amino acids is discussed. PMID- 3339108 TI - Quantitation of photochemically induced focal cerebral ischemia in the rat. AB - This study was carried out with a recently developed model of focal cerebral ischemia in the rat based on the photochemical induction of thrombotic stroke using the dye Rose Bengal. We examined the change in the volume of the lesion and brain water content, in separate groups of rats, at different times (1, 4, 24, 72, and 168 h) after the induction of the ischemic lesion. The volume of ischemic damage increased rapidly between 1 and 24 h after the ischemic insult and decreased between 24 and 168 h. The lesion at 168 h was significantly larger than that following 1 h of ischemia and similar to that obtained at 4 h, suggesting that the maximum extent of tissue damage (without the involvement of significant edema) was reached within the first 4 h in this model. The enlargement of the lesion after 4 h correlated closely with changes in brain water content. PMID- 3339109 TI - Divergent effects of the antiestrogen tamoxifen and of estrogens on luteinizing hormone (LH) pulse frequency, but not on basal LH levels and LH pulse amplitude in men. AB - We studied the role of estrogens on LH pulse modulation in men in two ways. Firstly, we compared LH pulse frequency and amplitude in 13 normal men before and after 6 weeks administration of the antiestrogen tamoxifen (10 mg twice daily). Secondly, we compared LH pulse frequency and amplitude between a group of 10 agonadal men not receiving sex steroid treatment and a group of 9 agonadal men (male to female transsexuals) continuously treated with 50 micrograms ethinyl estradiol/day. Tamoxifen administration to normal men resulted in a significant rise in the mean serum LH level from 5.7 +/- 1.3 (+/- SD) to 10.1 +/- 2.4 U/L, which was associated with significant increases in LH pulse frequency (from 4.2 +/- 1.5 to 5.8 +/- 1.7/7 h) and LH pulse amplitude (from 3.8 +/- 0.9 to 4.6 +/- 0.7 U/L). In the group of agonadal men the mean LH pulse frequency was 6.8 +/- 1.5/7 h, while it was 5.9 +/- 1.7/7 h in the estrogen-treated agonadal group (P = NS). The mean serum LH level and LH pulse amplitude were, however, significantly lower in the estrogen-treated agonadal men than in the agonadal men (14.7 +/- 7.0 vs. 34.3 +/- 8.6 and 4.1 +/- 1.8 vs. 7.4 +/- 1.8 U/L, respectively). We conclude that estrogens reduce basal LH levels and LH pulse amplitude. With regard to the modulation of LH pulse frequency our data provide contradictory results. While an antiestrogen increased LH pulse frequency in normal men, estrogen alone produced no change in LH pulse frequency in agonadal men. The study design in the agonadal men ignores the possible interaction of the two major testicular hormones (estradiol and testosterone) on gonadotropin secretion. Therefore, a possible explanation for this discrepancy in the effects of antiestrogen and estrogen could be an interaction between estrogens and androgens on gonadotropin secretion at the level of the LHRH pulse generator. PMID- 3339110 TI - Thyroid, parathyroid, and salivary gland evaluations in patients exposed to multiple fluoroscopic examinations during tuberculosis therapy: a pilot study. AB - The prevalence of thyroid, parathyroid, and salivary abnormalities was determined in 91 women who received an average of 112 fluoroscopic chest examinations during pneumothorax treatment for tuberculosis more than 40 yr previously and in 72 women treated for tuberculosis by other modalities. Thyroid abnormalities were determined by physical examination, scintiscans, and measurements of serum free T4 index, TSH, and thyroid microsomal antibodies. Thyroid nodules were diagnosed in 7.7% of the exposed and 4.2% of the comparison group (prevalence ratio, 1.8; 90% confidence interval 0.6-5.7). Autoimmune thyroid disease was diagnosed in 15.2% of the exposed and 6.9% of the comparison group (prevalence ratio, 2.2; 95% confidence interval, 0.8-6.2). No salivary tumors were detected. Two exposed women and 1 comparison woman had primary hyperparathyroidism. Although absorbed dose to the thyroid could not be precisely determined, approximately 60 rads would be expected to yield the observed excess of thyroid nodules. While the prevalence ratios were not significantly increased in the exposed group, the results suggest that susceptibility of the thyroid to nodules from cumulative radiation doses of this magnitude could be increased even when the doses are accumulated over years and that such x-ray exposure of the thyroid gland may predispose the patient to the development of autoimmune disease. PMID- 3339111 TI - Hormonal and developmental regulation of adrenodoxin messenger ribonucleic acid in steroidogenic tissues. AB - Adrenodoxin is an iron-sulfur protein found in the mitochondria of steroidogenic tissues. It participates in steroidogenesis as an electron transport intermediate for mitochondrial cytochromes P450, including P450scc, the cholesterol side-chain cleavage enzyme. Using a human adrenodoxin cDNA probe recently cloned in our laboratory, we examined the distribution and hormonal regulation of adrenodoxin mRNA in a variety of steroidogenic tissues. Adrenodoxin mRNA was found in all steroidogenic tissues examined. In human fetal testes, adrenodoxin mRNA was more abundant in early gestation, diminishing toward midterm in a pattern closely similar to that we reported previously for P450scc. Unlike P450scc, however, significant amounts of adrenodoxin mRNA were detected in human fetal ovaries, with no discernible gestation-dependent change. The abundance of adrenodoxin mRNA was increased in cultured human granulosa cells by treatment with hCG, FSH, cAMP, and cholera toxin. In human fetal adrenal cells, ACTH and cAMP stimulated accumulation of adrenodoxin mRNA, while in cultured human fetal testicular cells and cultured fetal rhesus monkey ovarian cells, both hCG and cAMP stimulated accumulation of adrenodoxin mRNA. In all of these systems, the accumulation of adrenodoxin mRNA closely paralleled the response of P450scc. These data suggest that the genes for these functionally related but structurally unrelated proteins are regulated in a coordinate manner. PMID- 3339112 TI - Cholinergic muscarinic receptor blockade suppresses arginine- and exercise induced growth hormone secretion in type I diabetic subjects. AB - Stimulatory cholinergic pathways participate in the regulation of GH release, and cholinergic receptor antagonists inhibit GH secretion in normal man. Whether similar mechanisms are active in subjects with insulin-dependent diabetes is not known, yet this is of potential importance since GH hypersecretion has been implicated in both the acute and chronic complications of diabetes mellitus. To address this question we studied the effects of cholinergic receptor blockade on stimulated GH release in 18 type I diabetic men. Paired tests were performed using 1 of 2 different stimuli (30 g arginine, iv, or physical exercise for 30 min) with or without prior administration of the selective cholinergic muscarinic receptor antagonist pirenzepine (30 mg, iv). Arginine elicited a mean peak serum GH level of 9.0 +/- 1.9 (+/- SEM) micrograms/L, which was completely suppressed by pirenzepine (1.5 +/- 0.4 micrograms/L; n = 8; P less than 0.01). Blood glucose rose after arginine infusion and was not affected by pirenzepine. Serum GH levels rose during physical exercise to a mean peak of 7.3 +/- 1.6 micrograms/L, which was abolished by pirenzepine (1.2 +/- 0.3 micrograms/L; n = 10; P less than 0.01). Blood glucose was not influenced by pirenzepine. Two subjects had no serum GH response to exercise. We conclude that GH secretion in subjects with insulin dependent diabetes, as in normal subjects, is modulated by cholinergic pathways and is responsive to pharmacological suppression by muscarinic receptor blockade. This may have implications for therapeutic trials designed to lower elevated GH levels in subjects with diabetes mellitus. PMID- 3339113 TI - Effects of endogenous sex steroids on serum lipoproteins and postheparin plasma lipolytic enzymes. AB - Sex steroids influence serum high density cholesterol (HDL) concentrations through their effects on postheparin plasma hepatic lipase activity. This enzyme is remarkably sex steroid sensitive; its activity is increased by treatment with androgens and androgenic progestins but decreased by estrogens. Hepatic lipase also is regulated by endogenous estradiol, but less is known about its regulation by endogenous androgens. We measured serum lipoproteins and postheparin plasma hepatic lipase and lipoprotein lipase activities in relation to sex steroids in 13 boys in whom testicular sex steroid production was stimulated by 4 injections of hCG given at 3-day intervals. Serum testosterone, but not estradiol, concentrations increased in 8 boys (group I, prepubertal and early pubertal boys), whereas in 5 boys both testosterone and estrogen concentrations increased concomitantly (group II, pubertal boys). Postheparin plasma hepatic lipase activity increased by 34% (P less than 0.001) in group I, but did not change in group II. Serum HDL cholesterol concentrations did not change during hCG stimulation. However, postheparin plasma hepatic lipase activity correlated inversely with serum HDL (r = -0.34; P less than 0.05) and HDL2 cholesterol levels (r = -0.51; P less than 0.001), and the changes in HDL2 levels and hepatic lipase activity were inversely related (r = -0.63; P less than 0.05). Postheparin plasma lipoprotein lipase activity decreased during hCG stimulation. Its activity was positively related to HDL (r = 0.47; P less than 0.05) and HDL2 cholesterol levels (r = 0.54; P less than 0.001). These results suggest that endogenous androgens and estrogens are involved in the regulation of postheparin plasma lipase activities and serum HDL cholesterol concentrations. PMID- 3339114 TI - Physiological profiles of episodic progesterone release during the midluteal phase of the human menstrual cycle: analysis of circadian and ultradian rhythms, discrete pulse properties, and correlations with simultaneous luteinizing hormone release. AB - To define the physiological relationships between episodic progesterone and LH release, we measured serum progesterone and LH concentrations in blood sampled at 10-min intervals for 24 h in seven young women in the midluteal phase of the menstrual cycle. The resultant time series were assessed further by Fourier transformation, Cluster analysis, and cross-correlation analysis with autoregressive modeling. These techniques permitted an examination of circadian rhythms, discrete (ultradian) pulse properties, and simultaneous or lagged correlations between progesterone and LH release. We found the following. 1) Both serum LH and progesterone concentrations had significant circadian periodicities, with similar acrophases (times of maximal nyctohemeral values). LH and progesterone also manifested multiple ultradian rhythms of similar periodicities (range, 48-241 min). 2) Discrete serum progesterone peaks occurred at a mean interpulse interval of 118 +/- 12 (+/- SE) min, had durations of 92 +/- 12 min, and had incremental amplitudes of 4.3 +/- 0.9 ng/mL (14 +/- 3 nmol/L). The frequency and duration characteristics of the progesterone and LH peaks were not significantly different, but progesterone fractional peak amplitudes were one quarter those of LH pulses. 3) Fractional progesterone peak amplitudes in the seven women correlated inversely (r = -0.811) with 24-h mean LH concentrations, suggesting a negative feedback relationship between progesterone and LH release. 4) LH and progesterone interpulse intervals both exhibited significant nyctohemeral variations, with diurnal amplitudes of 73 +/- 12 min for LH and 43 +/- 8.9 min for progesterone (P less than 0.01). 5) Significant positive cross correlations existed in all seven women between serum LH and progesterone concentrations considered simultaneously and at progesterone time lags of 10-50 min. By autoregressive modeling, the later (20-50 min) cross-correlations could be accounted for by sustained autocorrelations in the individual progesterone and LH time series and significant cross-correlations between LH and simultaneous progesterone concentrations and between LH and 10-min lagged progesterone concentrations. We conclude that progesterone release occurs in a periodic (circadian and ultradian) fashion as well as in a discrete (episodic or pulsatile) mode. Moreover, both positive and negative feedback relationships operate to coordinate LH and progesterone secretion in the midluteal phase of the human menstrual cycle. PMID- 3339115 TI - Increased plasma and cerebrospinal fluid norepinephrine in older men: differential suppression by clonidine. AB - To evaluate the effect of advanced age on central nervous system noradrenergic activity, cerebrospinal fluid (CSF) and plasma norepinephrine (NE) concentrations were measured concurrently in 14 older [mean, 65 +/- 9 (+/- SD) yr] and 33 younger (25 +/- 2 yr) normal men. CSF NE was significantly higher in older men than in young men [214 +/- 75 (+/- SD) vs. 164 +/- 56 pg/mL (1.26 +/- 0.44 vs. 0.97 +/- 0.33 nmol/L); P less than 0.02] as was plasma NE [282 +/- 103 vs. 211 +/ 63 pg/mL (1.67 +/- 0.61 vs. 1.25 +/- 0.37 nmol/L); P less than 0.02]. Subgroups of young and older men underwent two lumbar punctures, one of which was performed 100 min after the administration of 5 micrograms/kg oral clonidine. The young (n = 7) and older (n = 7) men had similar plasma clonidine levels [1.0 +/- 0.1 vs. 0.8 +/- 0.1 ng/mL (4.35 +/- 0.43 vs. 3.48 +/- 0.78 nmol/L)] and CSF clonidine levels [0.18 +/- 0.02 vs. 0.22 +/- 0.03 ng/mL (0.78 +/- 0.09 vs. 0.96 +/- 0.13 nmol/L)]. The suppression of CSF NE by clonidine was significantly greater (P less than 0.015) in young men [189 +/- 44 to 104 +/- 26 pg/mL (1.12 +/- 0.26 to 0.62 +/- 0.15 nmol/L)] than in older men [190 +/- 49 to 164 +/- 58 pg/mL (1.12 +/ 0.29 to 0.97 +/- 0.34 nmol/L)]. In contrast, the suppression of plasma NE by clonidine did not significantly differ between young [242 +/- 72 to 93 +/- 24 pg/mL (1.43 +/- 0.43 to 0.55 +/- 0.14)] and older men [285 +/- 102 to 167 +/- 84 pg/mL (1.68 +/- 0.60 to 0.99 +/- 0.50 nmol/L)]. These data suggest that decreased sensitivity of alpha 2-adrenergic mechanisms regulating CNS noradrenergic activity may contribute to increased CNS noradrenergic activity with aging. PMID- 3339116 TI - Estrogen-induced prolactinoma in a man. AB - Prolactinomas can be induced in rats by large doses of estrogens. Whether prolactinomas can be induced in humans by estrogens, however, is not known. This report describes the development of a prolactinoma in a man with previously normal plasma PRL levels after the administration of pharmacological doses of estrogen. The patient, a 26-yr-old male to female transsexual, took cyproterone acetate (100 mg/day, orally) and ethinyl estradiol (100 micrograms/day, orally) for 10 months and (surrepititiously) estradiol-17-undecanoate (100 mg, twice weekly, im) for about 6 of the 10 months. Plasma PRL levels rose from 0.05 to 5.20 U/L within 10 months (normal, 0.05-0.30 U/L). A computed tomographic scan showed a pituitary mass with suprasellar extension. After all estrogen therapy was discontinued, his plasma estradiol levels gradually declined from 2.8 to 0.77 nmol/L (normal, 0.04-0.12 nmol/L), but PRL levels rose further to 6.2 U/L. Bromocriptine treatment (2.5 mg twice daily) then was given. Plasma PRL fell gradually to 0.43 U/L and a computed tomographic scan after 5 months showed reduction in tumor size. The patient then discontinued bromocriptine treatment. Four months later his plasma estradiol level was normal, while plasma PRL had risen to 4.6 U/L, indicating autonomous PRL secretion. We conclude that 1) estrogen in pharmacological doses can induce prolactinomas in man; and 2) subjects treated with high doses of estrogen must, therefore, be surveyed for the development of such tumors. PMID- 3339118 TI - Production of immunoglobulin G and increased antiviral antibody in cerebrospinal fluid of dogs with delayed-onset canine distemper viral encephalitis. AB - Sera and cerebrospinal fluid (CSF) from four dogs with delayed-onset canine distemper viral (CDV) encephalitis (old dog encephalitis) were compared with samples from dogs with acute CDV and from recently vaccinated controls. Dogs with old dog encephalitis (ODE) had elevated CSF IgG concentrations (122 micrograms/ml) compared to controls (13 micrograms/ml) without elevated CSF albumin; their CSF IgG index was significantly greater. CSF proteins banding in the alkaline region of isoelectric focusing gels were immunochemically identified as IgG. Detectable viral neutralizing antibody was present in ODE CSF, and formed a larger proportion of IgG in CSF than in serum. Serum samples containing 2 mg IgG bound to all viral polypeptides of both R252 and Onderstepoort CDV isolates by immunoblot analysis. CSF samples of ODE patients bound viral antigens when diluted to contain as little as 5-40 micrograms IgG, while patient serum could be diluted to 40-200 micrograms IgG content compared to serum IgG of 100 micrograms/ml in vaccinated controls. Serial CSF dilutions consistently bound to H and NP polypeptides at the highest dilutions, similar to the binding of serums from recently vaccinated dogs. Thus, dogs with delayed-onset CDV encephalitis have elevated concentrations of CSF IgG, much of which is virus-specific, with an antigen binding pattern similar to that of sera of recently immunized dogs. PMID- 3339117 TI - Synthetic and partially-purified adenylate cyclase-stimulating proteins from tumors associated with humoral hypercalcemia of malignancy inhibit phosphate transport in a PTH-responsive renal cell line. AB - Hypophosphatemia and hyperphosphaturia characteristically occur in patients with humoral hypercalcemia of malignancy (HHM). To determine if a tumor product causes these abnormalities in phosphate metabolism, rather than, for example, hypercalcemia, we investigated the effect of partially-purified adenylate cyclase stimulating activity (ACSA) from human and animal HHM-associated tumors on sodium dependent phosphate transport (Na PiT) in a PTH-responsive renal epithelial cell line. Thirty minute exposure to 7 X 10(-10) MbPTH (1-34) equivalents of ACSA from the human and animal tumors, reduced NaPiT by 20% and 14%, respectively. We also recently isolated an adenylate cyclase-stimulating protein (hACSP) from two human tumors associated with HHM and identified a cDNA clone for this protein which encodes a 141 amino-acid peptide. Based on the deduced amino-acid sequence, we synthesized tyr36 (1-36) hACSP. This synthetic peptide induced a 22% decrease in the initial rate of NaPiT by the epithelial monolayer. Its inhibitory activity was roughly equipotent to that of bPTH (1-34). We conclude that the ACSP derived from HHM-associated tumors decreases phosphate transport in renal epithelial cells. This peptide appears to play a key role in mediating the changes in phosphate metabolism in this syndrome. PMID- 3339119 TI - Muscarinic receptors and receptor-mediated actions on rat thymocytes. AB - Rat thymocytes possess a single class of saturable, high affinity binding sites for muscarinic antagonists of the benzilate type such as [3H]3-quinuclidinyl benzilate ([3H]3-QNB). The average number of receptors per cell is 3000 and the equilibrium dissociation constant of [3H]3-QNB on intact cells is 7.5 nM. In the work reported here we found that perturbation of the thymocyte membrane by addition of phytohemagglutinin (4 micrograms/ml) caused a transient increase in muscarinic antagonist binding, and hydrocortisone (100 mg/kg s.c.) treatment of rats for 2 days prior to sacrifice increased the average number of muscarinic receptor sites on thymocytes by 100%. Atropine treatment, which in other tissues causes increased muscarinic receptor concentration, did not alter the receptor number on thymocytes. Binding of carbachol to the receptor on intact cells resulted in inhibition of cAMP synthesis and stimulation of cGMP synthesis. These muscarinic agonist effects were each inhibited by the simultaneous addition of the muscarinic antagonist atropine (5 X 10(-5) M). No stimulation of phosphatidylinositol turnover by muscarinic agonists was observed. PMID- 3339120 TI - Rat thymocytes release a factor which inhibits muscarinic ligand binding. AB - Rat thymocytes incubated in RPMI medium for 120-300 min release a soluble factor of molecular weight below 10,000 Da which inhibits the binding of 3H-labeled muscarinic antagonists in an uncompetitive manner, i.e. it reduces maximal specific binding (Bmax) without changing the affinity of the ligand (KD). This factor inhibited muscarinic antagonist binding on thymocytes and rat cerebral cortex cellular membranes. Thymocytes from hydrocortisone-treated rats produced more factor per mg cell protein than thymocytes from untreated rats. The activity of the factor was unaffected by incubation with Cd2+ (1 mM) or Zn2+ (1 mM) or EDTA (1 mM), and its protein nature is supported by the following findings: it was trypsin sensitive, heat denaturated at 56 degrees C and precipitated by (NH4)2SO4 (40%, w/v). Inhibition by the factor was apparently irreversible after 1 h of incubation. PMID- 3339121 TI - Presence of an autoantibody against a Golgi cisternal membrane protein in the serum and cerebrospinal fluid from a patient with idiopathic late onset cerebellar ataxia. AB - Tissue and cultured cells of different species and embryological origins incubated with serum (diluted up to 10,000-fold) or cerebrospinal fluid (CSF) (6 fold dilution) from a 48-year-old female patient with idiopathic late-onset cerebellar ataxia, exhibited a bright specific perinuclear staining when studied by indirect immunofluorescence microscopy. The pattern of the staining was that characteristic of the Golgi apparatus, consisting of a crescent-shaped juxtanuclear reticulum located in the vicinity of the microtubule organizing center. Changes in location and organization of the organelle stained by the patient's serum during mitosis or after incubation of the cells with Colcemid, taxol or monensin, resulted in a disruption of the reticulum that followed the expected patterns for Golgi apparatus. The staining was specifically absorbed with Golgi cisternae-enriched membrane fractions. Finally, dot-immunoblotting studies of membrane and soluble fractions of Golgi cisternae and vesicles showed that the anti-Golgi antibody (AGA) reacted with the cytoplasmic domain of an integral membrane protein contained in the Golgi cisternae. The presence of this unusual autoantibody in an idiopathic late-onset cerebellar ataxia-bearing patient can afford some insights into the pathogenesis of these neurological diseases. PMID- 3339122 TI - Metabolism of cerebroside sulfate and subcellular distribution of its metabolites in cultured skin fibroblasts from controls, metachromatic leukodystrophy, and globoid cell leukodystrophy. AB - With pulse-chase study of 1-[14C]stearic acid-labeled cerebroside sulfate (14C CS) and subsequent subcellular fractionation by Percoll gradient, the metabolism of CS and translocation of its metabolites in human skin fibroblasts from controls, metachromatic leukodystrophy (MLD), and globoid cell leukodystrophy (GLD) were studied. In control skin fibroblasts, CS was transported to lysosome and metabolized there to galactosylceramide (GalCer) and ceramide (Cer) within 1 h. During the chase period, radioactivity was increased at plasma membrane plus Golgi as phospholipids and no accumulation of GalCer or Cer was found in lysosome. In MLD fibroblasts, 95% of 14C-CS taken up was unhydrolyzed at 24 h chase and accumulated at not only lysosome but also plasma membrane. In GLD fibroblasts, GalCer was accumulated throughout the subcellular fractions and more accumulated mainly at plasma membrane plus Golgi with longer pulse. This translocation of lipid from lysosome seems to have considerable function, even in lipidosis, which may result in an imbalance of the sphingolipid pattern on the cell surface and these changes might be one of causes of neuronal dysfunction in sphingolipidosis. PMID- 3339123 TI - High efficiency covalent radiolabeling of the human androgen receptor. Studies in cultured fibroblasts using dihydrotestosterone 17 beta-bromoacetate. AB - Analysis of mutations affecting the androgen receptor protein in human cells has been limited because of the low abundance and lability of these proteins in target tissues. All methods used to date have been based on the noncovalent interaction of radiolabeled androgens with the receptor's ligand binding site. We report here synthesis and use of the electrophilic affinity label dihydrotestosterone 17 beta-bromoacetate. This ligand, prepared as a radioactive compound of high specific activity, rapidly and covalently binds to a protein of 58,000 daltons in cytosol from normal genital skin fibroblasts. This protein is a high affinity, saturable specific binding site for the ligand and was not detectable in cultured cells from a subject with androgen resistance or in receptor-negative nongenital fibroblasts. The efficiency of incorporation of the covalent radiolabel into the 58-kD protein is greater than 80% based on estimates of receptor content using noncovalent ligands in intact cell assays. These studies demonstrate that dihydrotestosterone 17 beta-bromoacetate is useful for high efficiency covalent labeling of the human androgen receptor in crude cytosolic extracts from cultured cells. PMID- 3339124 TI - Histopathological heterogeneity of neuropathy in insulin-dependent and non insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy. AB - Altered sorbitol and myo-inositol metabolism, (Na,K)-ATPase function, electrochemical sodium gradients, axonal swelling, and distortion and disruption of the node of Ranvier ("axo-glial dysjunction") directly implicate hyperglycemia in the pathogenesis of neuropathy in diabetic rats, but the relevance of this sequence to clinical neuropathy in heterogeneous groups of diabetic patients remains to be established. Fascicular sural nerve morphometry in 11 patients with neuropathy complicating insulin-dependent diabetes revealed a pattern of interrelated structural changes strikingly similar to that of the diabetic rat when compared to age-matched controls. 17 older non-insulin-dependent diabetic patients with comparable duration and severity of hyperglycemia and severity of neuropathy, displayed similar nerve fiber loss, paranodal demyelination, paranodal remyelination and segmental demyelination compared to age-matched controls, but axo-glial dysjunction was replaced by Wallerian degeneration as the primary manifestation of fiber damage, and fiber loss occurred in a spatial pattern consistent with an ischemic component. The mechanistic model developed from the diabetic rat does indeed appear to apply to human diabetic neuropathy, but superimposed hormonal, metabolic, vascular, and/or age-related effects alter the morphologic expression of the neuropathy in non-insulin dependent diabetes. PMID- 3339125 TI - Effects of a high potassium diet on electrical properties of cortical collecting ducts from adrenalectomized rabbits. AB - The cortical collecting tubule is one of the main nephron sites where mineralocorticoids and a high potassium diet modulate sodium (Na) and potassium (K) transport. In this study we explored the steroid-independent effects of a high K diet on the electrical transport properties of the isolated rabbit cortical collecting tubule principal cells. The electrophysiological analysis included transepithelial and single-cell potential measurements and equivalent circuit analysis. Rabbits were adrenalectomized (ADX) and received either a control diet (300 meq K/kg diet) or a high K diet (600 meq/kg diet) for 10 d before the experiment. The mean plasma K of ADX control animals was 6.9 mM, that of ADX animals on the high K diet 8.3 mM. The transepithelial potential difference was significantly elevated in the high K group (-3.5 mV, lumen negative), compared with ADX controls (-1.4 mV). The basolateral membrane potential in high K animals was also significantly elevated (-73 mV, cell negative, compared with -63 mV in controls). Estimates of the apical membrane partial Na and K conductances (GaNa and GaK) and of ion currents (IaNa and IaK) also demonstrated stimulation by the high K diet. In the high K group, both GaNa and GaK (0.56 and 2.67 mS.cm-2) were higher than control values (0.27 and 1.17 mS.cm-2). IaNa and IaK were also higher in high K animals (47.8 and -26.2 microA.cm-2) compared with control animals (22.4 and -11.6 microA.cm-2). Thus, a high K intake per se can induce electrophysiological changes consistent with stimulation of Na reabsorption and K secretion. PMID- 3339126 TI - Transsulfuration in an adult with hepatic methionine adenosyltransferase deficiency. AB - We investigated sulfur and methyl group metabolism in a 31-yr-old man with partial hepatic methionine adenosyltransferase (MAT) deficiency. The patient's cultured fibroblasts and erythrocytes had normal MAT activity. Hepatic S adenosylmethionine (SAM) was slightly decreased. This clinically normal individual lives with a 20-30-fold elevation of plasma methionine (0.72 mM). He excretes in his urine methionine and L-methionine-d-sulfoxide (2.7 mmol/d), a mixed disulfide of methanethiol and a thiol bound to an unidentified group X, which we abbreviate CH3S-SX (2.1 mmol/d), and smaller quantities of 4-methylthio 2-oxobutyrate and 3-methylthiopropionate. His breath contains 17-fold normal concentrations of dimethylsulfide. He converts only 6-7 mmol/d of methionine sulfur to inorganic sulfate. This abnormally low rate is due not to a decreased flux through the primarily defective enzyme, MAT, since SAM is produced at an essentially normal rate of 18 mmol/d, but rather to a rate of homocysteine methylation which is abnormally high in the face of the very elevated methionine concentrations demonstrated in this patient. These findings support the view that SAM (which is marginally low in this patient) is an important regulator that helps to determine the partitioning of homocysteine between degradation via cystathionine and conservation by reformation of methionine. In addition, these studies demonstrate that the methionine transamination pathway operates in the presence of an elevated body load of that amino acid in human beings, but is not sufficient to maintain methionine levels in a normal range. PMID- 3339127 TI - Pyrimidine base degradation in cultured murine C-1300 neuroblastoma cells and in situ tumors. AB - Dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting step in pyrimidine degradation, was studied in two cell lines of murine neuroblastoma (MNB-T1 and MNB-T2) that were derived from C-1300 MNB tumor carried in A/J mice. The MNB-T2 (low malignancy) cell line was originally derived from the in situ tumor and carried in tissue culture for more than 100 passages; the MNB-T1 (high malignancy) line consisted of a new sub-culture that was also established from the in situ MNB tumor. DPD activity was determined in cytosolic preparations of MNB utilizing high performance liquid chromatography to separate the radiolabeled substrate ([2-14C]thymine) from [2-14C]dihydrothymine. The apparent affinity of DPD for NADPH in MNB cells (Km approximately 0.08 mM) was identical to that of A/J mouse brain and liver. The DPD activity of the high malignancy (MNB-T1) cell line was 14.3% of that observed in the low malignancy (MNB-T2) line. In situ tumors formed after implantation of high malignancy (MNB-T1) cells into A/J mice had only 25.2% of the DPD activity observed in tumors derived from low malignancy (MNB-T2) cells. When MNB-T2 cells were injected into naive A/J mice, tumors developed in only 68% of animals, the tumor growth rate was slow and a mortality of 20% was observed. In contrast, tumors derived from injected MNB-T1 cells showed a faster growth rate and 100% mortality. Most MNB-T2 derived tumors were not lethal and ultimately resolved while the MNB-T1 derived tumors were invariably lethal. These studies support the concept that the levels of DPD activity in neoplastic cells are inversely related to their malignant expression and also provide a model to study differences between neuroblastoma cell lines derived from the same in situ tumor but which manifest different neoplastic behavior. PMID- 3339128 TI - Increased renal catabolism of 1,25-dihydroxyvitamin D3 in murine X-linked hypophosphatemic rickets. AB - The hypophosphatemic (Hyp) mouse, a murine homologue of human X-linked hypophosphatemic rickets, is characterized by renal defects in brush border membrane phosphate transport and vitamin D3 metabolism. The present study was undertaken to examine whether elevated renal 25-hydroxyvitamin D3-24-hydroxylase activity in Hyp mice is associated with increased degradation of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] by side chain oxidation. Metabolites of 1,25(OH)2D3 were separated by HPLC on Zorbax SIL and identified by comparison with standards authenticated by mass spectrometry. Production of 1,24,25 trihydroxyvitamin D3, 24-oxo-1,25-dihydroxyvitamin D3, and 24-oxo-1,23,25 trihydroxyvitamin D3 was twofold greater in mitochondria from mutant Hyp/Y mice than from normal +/Y littermates. Enzyme activities, estimated by the sum of the three products synthesized per milligram mitochondrial protein under initial rate conditions, were used to estimate kinetic parameters. The apparent Vmax was significantly greater for mitochondria from Hyp/Y mice than from +/Y mice (0.607 +/- 0.064 vs. 0.290 +/- 0.011 pmol/mg per protein per min, mean +/- SEM, P less than 0.001), whereas the apparent Michaelis-Menten constant (Km) was similar in both genotypes (23 +/- 2 vs. 17 +/- 5 nM). The Km for 1,25(OH)2D3 was approximately 10-fold lower than that for 25-hydroxyvitamin D3 [25(OH)D3], indicating that 1,25(OH)2D3 is perhaps the preferred substrate under physiological conditions. In both genotypes, apparent Vmax for 25(OH)D3 was fourfold greater than that for 1,25(OH)2D3, suggesting that side chain oxidation of 25(OH)D3 may operate at pharmacological concentrations of substrate. The present results demonstrate that Hyp mice exhibit increased renal catabolism of 1,25(OH)2D3 and suggest that elevated degradation of vitamin D3 hormone may contribute significantly to the clinical phenotype in this disorder. PMID- 3339130 TI - Glucocorticoid regulation of insulin receptor gene transcription in IM-9 cultured lymphocytes. AB - We have reported that glucocorticoids increase steady state insulin receptor mRNA levels in target cells. In the present study using IM-9 cultured human lymphocytes, we investigated the mechanism responsible for this glucocorticoid mediated increase in insulin receptor mRNA levels. Incubation of IM-9 cells with 100 nM dexamethasone for 4 h stimulated a parallel increase in both polysomal and nuclear insulin receptor RNAs indicating that glucocorticoids did not alter the nuclear transport of insulin receptor RNA. Dexamethasone did not alter insulin receptor mRNA half life (t 1/2 = 140 +/- 20 min), indicating that glucocorticoids did not influence mRNA stability. Furthermore, the dexamethasone-induced increase in insulin receptor mRNA levels was not blocked by pretreatment of cells with cycloheximide indicating that the glucocorticoid effect was independent of new protein synthesis. When the labeled transcripts from nuclear run-off incubations were then hybridized to immobilize human insulin receptor cDNA, a three- to fourfold increase in transcriptional activity was observed. This transcriptional effect occurred before the increase in steady state insulin receptor mRNA levels and over the same range of dexamethasone concentrations. These studies indicate therefore a direct effect of glucocorticoids on insulin receptor gene transcription, and demonstrate that the insulin receptor gene is under hormonal control. PMID- 3339129 TI - Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. AB - To determine if levels of serum total homocysteine are elevated in patients with either cobalamin or folate deficiency, we utilized a new capillary gas chromatographic-mass spectrometric technique to measure total homocysteine in the serum of 78 patients with clinically confirmed cobalamin deficiency and 19 patients with clinically confirmed folate deficiency. Values ranged from 11 to 476 mumol/liter in the cobalamin-deficient patients and 77 of the 78 patients had values above the normal range of 7-22 mumol/liter as determined for 50 normal blood donors. In the cobalamin-deficient patients, serum total homocysteine was positively correlated with serum folate, mean corpuscular volume, serum lactate dehydrogenase, serum methylmalonic acid, and the degree of neurologic involvement, and inversely correlated with platelets and hematocrit. In the folate-deficient patients, values for serum total homocysteine ranged from 17 to 185 mumol/liter and 18 of the 19 patients had values above the normal range. Some patients with pernicious anemia who were intermittently treated with cyanocobalamin were found to have elevated serum levels of total homocysteine while they were free of hematologic and neurologic abnormalities. The measurement of serum total homocysteine will help define the incidence of cobalamin deficiency and folate deficiency in various patient populations. PMID- 3339131 TI - Synthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats. AB - Parathyroid hormone-like adenylate cyclase-stimulating proteins (hACSPs) have been implicated as one of the calcemic, bone-resorbing agents in patients with humoral hypercalcemia of malignancy. We report the synthesis of an amino-terminal hACSP fragment, Tyr36 hACSP (1-36) amide. The synthetic hACSP is a potent agonist of renal membrane adenylate cyclase (Km, 1.7 X 10(-10)) and of bone cell adenylate cyclase (Km 1 X 10(-9)M). It is a potent bone-resorbing agent in vitro, stimulating 45Ca release from fetal rat long bones at a concentration of 10(-9) M. When infused via osmotic minipumps into rats, it is also a potent calcemic factor in vivo, inducing a rise in serum calcium from (mean +/- SD) 10.6 +/- 0.6 to 19.7 +/- 3.2 mg/dl when infused at 1.4 micrograms/h and from 9.9 +/- 0.7 to 11.4 +/- 1.2 mg/dl when infused at 0.14 micrograms/h. These findings indicate that biologically active hACSP fragments can be synthesized. One such synthetic peptide possesses the in vitro and in vivo bioactivities demonstrated in native, tumor-derived hACSPs. It is also a potent calcemic, bone-resorbing agent. PMID- 3339132 TI - Low density lipoproteins transfer bacterial lipopolysaccharides across endothelial monolayers in a biologically active form. AB - Rabbit aortic endothelial cells (RAECs) were grown on micropore filters in a device that allowed in situ determination of transendothelial electrical resistance (TEER). Incubation of confluent RAEC monolayers with 2 ng.ml-1 of bacterial LPS for 3 h did not change the protein content or the number of cells on the filters, but resulted in a marked decline in TEER (from 14.1 +/- 0.9 to 5.1 +/- 0.6 omega.cm2) and a significant increase in LDL transport across the monolayers (from 154 +/- 13 to 456 +/- 41 ng. h-1 per cm2). In contrast, exposure of RAEC monolayers for 3 d to as much as 5 micrograms.ml-1 of LPS complexed to LDL (LPS-LDL) did not alter the TEER or LDL transport. LPS-LDL was transported across the monolayers at the same rate as LDL. While microgram quantities of LPS complexed to LDL did not disrupt the integrity of the endothelial monolayer, incubation of RAECs with transported LPS-LDL at concentrations of 25-100 ng LPS.ml-1 resulted in a two- to ninefold increase in the secretion of monocyte chemotactic activity by these cells. Incubation of rabbit aortic smooth muscle cells with transported LPS-LDL at concentrations of 25-100 ng LPS.ml-1 resulted in a two- to threefold increase in the secretion of monocyte chemotactic activity. We propose that LDL protects endothelial cells from the acute toxicity of LPS but the resulting complexes are transported across the endothelium in a biologically active form that can initiate an inflammatory response. PMID- 3339134 TI - Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney. AB - Erythropoietin (Epo)-producing cells were identified in the murine hypoxic kidney by in situ hybridization. Profound anemia was induced in order to greatly increase Epo production. This resulted in high levels of Epo mRNA in the kidney. 35S-labeled DNA fragments of the murine Epo gene were used as probes for in situ hybridization. Control experiments conducted in parallel included kidneys of nonanemic mice, RNase-treated hypoxic kidney sections, and 35S-labeled non-Epo related DNA. The Epo probe gave a specific hybridization signal in the hypoxic kidney in the cortex and to a lesser extent in the outer medulla. Glomerular and tubular cells were not labeled. All positive cells were identified as peritubular cells. Using immunofluorescence, we showed that cells with the same topography contained Factor VIII-related antigen. These data demonstrated that peritubular cells, most likely endothelial cells, constitute the major site of Epo production in the murine hypoxic kidney. PMID- 3339133 TI - Chronic granulomatous disease due to a defect in the cytosolic factor required for nicotinamide adenine dinucleotide phosphate oxidase activation. AB - The superoxide-generating enzyme of human neutrophils, NADPH oxidase, is present in a dormant state in unstimulated neutrophils. It can be converted to an active form in a cell-free system if both the plasma membrane and cytosol fractions are incubated together in the presence of arachidonic acid. This system was used to determine the nature of the biochemical defect in seven patients with the autosomal recessive, cytochrome b-positive form of chronic granulomatous disease (CGD). A severe deficiency in the cytosol factor was identified in each patient. The defective activity was not caused by the presence of an inhibitor, nor could it be restored to normal by combining cytosol fractions from different patients. In contrast, the membrane fractions from all seven patients contained normal levels of NADPH oxidase when activated in the presence of control cytosol. Of family members tested (obligate heterozygotes for this disorder), seven of eight had intermediate levels of cytosol factor activity. The respiratory burst defect in this form of CGD is caused by an abnormality in the cytosolic factor required for NADPH oxidase activation. PMID- 3339137 TI - Antiviral drugs and vaccines for herpes simplex and herpes zoster. Proceedings of a symposium. American Academy of Dermatology forty-fourth annual meeting. December 11, 1985, Las Vegas, NV. PMID- 3339135 TI - Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. AB - A monoclonal antibody (904) that binds to a leukocyte cell adhesion-promoting glycoprotein, (Mo1; CD11b/CD18) was administered (1 mg/kg, iv.) to open chest anesthetized dogs 45 min after the induction of regional myocardial ischemia. Ischemia was produced by occluding the left circumflex coronary artery (LCX) for 90 min and then reperfusing for 6 h. There was no difference between control and antibody treated groups with respect to arterial blood pressure, heart rate, or LCX blood flow. Administration of antibody produced no observable effect on circulating neutrophil counts, suggesting that antibody-bound neutrophils were not cleared from the circulation. The mean size of myocardial infarct expressed as percentage of the area at risk of infarction that resulted was reduced by 46% with anti-Mo1 treatment (25.8 +/- 4.7%, n = 8) compared to control (47.6 +/- 5.7%, n = 8; P less than 0.01). The area at risk of infarction was similar between groups. Circulating (serum) antibody excess was confirmed in all 8 anti Mo1 treated dogs by immunofluorescence analysis. Analysis of ST segment elevation on the electrocardiogram as an indicator of the severity of ischemia suggests that the anti-Mo1 reduces infarct size independent of the severity of ischemia. An additional group of dogs (n = 5) was tested with a control monoclonal antibody of the same subtype (murine IgG1) and was found to produce no significant reduction in myocardial infarct size. Accumulation of neutrophils within the myocardium was significantly attenuated with 904 treatment when analyzed by histological methods. These data demonstrate that administration of anti-Mo1 monoclonal antibody after the induction of regional myocardial ischemia results in reduced myocardial reperfusion injury as measured by ultimate infarct size. PMID- 3339138 TI - Psychiatric, legal, and moral issues of herpes simplex infections. AB - When patients first realize that they have genital herpes, they are likely to have a series of psychiatric reactions that include (1) denial, (2) a belief that there is a cure, (3) realization that they do have herpes, (4) loneliness, (5) anger toward their sexual partners, (6) fear of sexual deprivation, and (7) development of a poor self-image. One of the best coping mechanisms is to develop a social support system. Despite many concerns about sexual activities, the patient's work performance often goes on as before. By 1985, law suits by patients against those who allegedly gave them herpes had not resulted in awards at the Appeals Court level and one malpractice suit against physicians was not awarded. Genital infections in children must be regarded as potential child abuse by physicians. Morally, it is right for an infected person to disclose the existence of herpes to a potential partner but this is not always done for fear of compromising a relationship in its early phases. Because one's original infection may be asymptomatic, relating the time of acquisition of an infection to an act of infidelity cannot be judged solely on the basis of the time of the herpetic breakout. PMID- 3339139 TI - Treatment of mucocutaneous herpes simplex infections with acyclovir. AB - Topical acyclovir speeds healing and decreases viral shedding and pain in immunocompromised patients with chronic, ulcerative herpetic lesions; it may be used when one does not wish to add another systemic drug. In severe first-episode and life-threatening infections, acyclovir may be administered intravenously for 7 to 10 days. In milder and non-life-threatening first-episode infections, acyclovir may be given orally in a dosage of 200 mg five times a day for 10 days. With these doses, healing is 50% faster and viral shedding stops 90% sooner. Acyclovir given early during first-episode infections, especially true primary infections, may decrease immune responses to the virus, but these usually become normal later. Fewer than six recurrences a year may be managed by 200 mg acyclovir orally five times a day for 5 days beginning as soon as symptoms appear. More than six recurrences a year, often every month, may be managed by continuous suppressive oral acyclovir therapy. Kaposi's varicelliform eruption responds to acyclovir given orally or intravenously depending on circumstances. Primary and recurrent herpetic whitlow respond to acyclovir. PMID- 3339136 TI - An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina. AB - Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration caused by deficiency of the mitochondrial matrix enzyme, ornithine-delta-aminotransferase (OAT). To study the molecular basis of the mutations causing GA, we cloned and sequenced the human OAT cDNA and determined the intron-exon arrangement of the structural gene. Using the cDNA template, we synthesized antisense RNA probes and performed RNase A protection experiments with RNA from four Lebanese GA patients. We found a probe-target mismatch at the 5' end of the first coding exon and amplified this region of the patients' genomic DNA using the polymerase chain reaction. Sequence analysis showed a G----A transition, changing the initiator ATG (methionine) codon to ATA. This mutation segregates with the GA allele in both pedigrees. Initiation of translation at the closest in-frame methionine codon would truncate OAT by 138 amino acids, eliminating the entire mitochondrial leader sequence and 113 amino acids of the mature peptide. PMID- 3339141 TI - Adverse reactions to acyclovir: topical, oral, and intravenous. AB - Overall, acyclovir is a remarkably safe drug considering its potent antiviral effect. The most frequent reactions with short-term use of oral acyclovir are nausea and vomiting and with 6 months' use headache, diarrhea, nausea, and vomiting. These symptoms are also seen frequently with placebos. The most frequent adverse reaction to intravenous use has been inflammation and phlebitis at the injection site. The two most important serious adverse effects are (1) encephalopathic changes with abnormal electroencephalograms and lethargy, tremors, confusion, and seizures and (2) renal precipitation of the drug because of a rapid bolus of drug administered parenterally. Safety of acyclovir for use during pregnancy and in neonates and young children has not been established. PMID- 3339140 TI - Prophylactic and suppressive treatment with acyclovir and the management of herpes in patients with acquired immunodeficiency syndrome. AB - During 1 year of continuous suppressive therapy for frequent recurrent genital herpes, about 44% of patients taking 400 mg acyclovir twice a day had no recurrences and 4% of patients taking placebo had no recurrences (i.e., fewer patients taking acyclovir had recurrences, and when they did there were fewer recurrences). Toxicity of continuous suppressive acyclovir treatment appears to be minimal, and viral resistance developing to the drug during use of suppressive therapy has not been a problem, although it does occur. Patients with acquired immunodeficiency syndrome with recurrent herpes may be given 400 mg acyclovir five times a day for 5 days or until the eruption clears and then 400 mg three times a day for 1 or 2 months followed by 400 mg twice a day thereafter. Herpes zoster of immunocompromised patients, including patients with acquired immunodeficiency syndrome, may be treated with 800 mg oral acyclovir five or six times a day for 5 to 10 days depending on the response, and they may derive additional benefit from concomitant topical acyclovir. PMID- 3339142 TI - Acyclovir for recurrent erythema multiforme caused by herpes simplex. AB - Herpes-associated erythema multiforme can be controlled by continuous suppressive treatment with oral acyclovir. Erythema multiforme is not prevented if oral acyclovir is administered after a herpes simplex recurrence is evident and it is of no value after erythema multiforme has occurred. There is some question whether continuous topical treatment with acyclovir to sites of recurrent herpes will sometimes prevent erythema multiforme. Erythema multiforme may be precipitated by orolabial and genital recurrences and by recurrences on skin of the buttocks and other sites. Some herpetic recurrences are associated with erythema multiforme and some are not and episodes of erythema multiforme are not always associated with clinical herpetic recurrences. PMID- 3339143 TI - Antiviral treatment in chickenpox and herpes zoster. AB - Intravenous acyclovir is effective for varicella in adults and immunocompromised children, causing more rapid resolution of the illness and fewer complications. Intravenous acyclovir in immunocompromised patients with herpes zoster decreases new lesion formation, decreases acute pain, halts dissemination of the virus, and lessens visceral complications. Intravenous acyclovir may also be effective in zoster encephalitis. Intravenous vidarabine also has a favorable affect on chickenpox and herpes zoster. Topical acyclovir may benefit herpes zoster in immunosuppressed patients by accelerating cutaneous healing. Oral acyclovir appears to be effective in varicella and zoster in immunocompromised patients. It is also effective in otherwise normal patients, but its effect seems less dramatic and the drug must be given early. Neither acyclovir nor vidarabine has been proven clearly to prevent postherpetic neuralgia. Because varicella zoster virus is less sensitive to acyclovir than is herpes simplex, intravenous doses of 500 mg/m2 or 10 mg/kg every 8 hours or oral doses of 800 mg five times a day are recommended. At these doses adequate hydration and urine flow must be maintained, the mental status of the patient must be monitored, and impaired renal function requires regulation of dosage downward. PMID- 3339144 TI - Antiviral treatment of a serious herpes simplex infection: encephalitis. AB - Herpes simplex encephalitis is the most common cause of sporadic encephalitis in the western world. Patients usually have altered levels of consciousness, altered levels of mentation, fever, headache, and personality changes. These may progress to hemiparesis and seizures. Exact diagnosis must be established by brain biopsy and identification of the virus in biopsy material. There is a great need for a noninvasive test that is positive early in the disease. Without antiviral treatment the mortality rate is greater than 70%, and many survivors have serious disabilities. Both adenine arabinoside and acyclovir decrease death and morbidity, but acyclovir is the preferred drug. With acyclovir about 40% of patients will survive with normal development or minor levels of impairment but more than half of the patients will die or suffer significant impairment. It is essential to treat early; patients who are young and have not reached coma or impaired consciousness may show 65% recovery and return to normal function. Development of new antiviral drugs or other types of therapies is desirable. Herpetic skin lesions are likely to be more confusing than diagnostic because other types of encephalitis with fever often precipitate recurrent herpes that is unrelated to the encephalitis. PMID- 3339145 TI - Comments on vaccines, August 1987. AB - Because of latency and infectious recurrences, eradication of herpes simplex and herpes zoster from the world by vaccines is likely to be much more difficult to accomplish than eradication of smallpox. For some time we may have to settle for control of these diseases rather than their eradication. The live, attenuated varicella vaccine protects immunocompromised and normal persons against clinical chickenpox but it does not completely prevent subsequent infection with natural chickenpox virus or latency. With herpes simplex vaccines we may have to be satisfied with amelioration or control of clinical infections and diminution of latency and recurrent disease. Varicella zoster immune globulin plays a useful role in attenuation of varicella in immunocompromised or special-risk persons exposed to varicella zoster virus. Passive immunization for herpes simplex (herpes simplex immune globulin or other antibody preparations) has been studied very little. Maybe passive immunization will have a place in future therapies, especially for serious herpes simplex virus infections in immunocompromised hosts. PMID- 3339146 TI - Survival of the fittest. PMID- 3339147 TI - Fluid and electrolytes: assessment and interventions. PMID- 3339148 TI - Legislative news, views, and opinions. PMID- 3339149 TI - Urinary incontinence. PMID- 3339150 TI - Organization of the ostomy rehabilitation centers in Italy: current state and future perspectives. PMID- 3339151 TI - Management of pressure sores. PMID- 3339152 TI - Dermal wounds: pressure sores. Philosophy of the IAET. PMID- 3339153 TI - More on gloving. PMID- 3339154 TI - Trends in contraceptive use among university women, 1974-1983: a decade of change. PMID- 3339155 TI - AIDS: students' knowledge and attitudes at a midwestern university. PMID- 3339156 TI - A study of the relationship between mitral valve prolapse and personality characteristics. PMID- 3339157 TI - Marketing postsecondary health services. PMID- 3339159 TI - A physician's experience: taking care of Ralph. PMID- 3339158 TI - Life stress and depression in university students: clinical illustrations of recent research. PMID- 3339160 TI - AIDS: a sister's experience. PMID- 3339161 TI - Acute myocardial infarction associated with single vessel coronary artery disease: an analysis of clinical outcome and the prognostic importance of vessel patency and residual ischemic myocardium. AB - The long-term outcome and the significance of residual ischemic myocardium, as assessed by predischarge exercise thallium scintigraphy and vessel patency, were studied in 97 patients with single vessel coronary artery disease by angiography 12 +/- 4 days after uncomplicated myocardial infarction. During a mean follow-up period of 39 +/- 17 months, no patients died, 6 (6%) had a recurrent nonfatal infarction and 25 (26%) experienced rapidly progressive angina requiring hospitalization. Although neither exercise-induced angina nor ST segment depression was predictive of a recurrent cardiac event, the mean number of infarct zone scan segments showing thallium redistribution (1.0 +/- 1.0 versus 0.5 +/- 0.8, p = 0.01) and the percent of patients with infarct zone redistribution (61 versus 39%, p = 0.05) were greater in those patients who experienced a late ischemic event. Kaplan-Meier analysis demonstrated a lower event-free survival rate in patients with redistribution (n = 45) than in those without redistribution (n = 52) (p = 0.019). Although no patient received immediate thrombolytic therapy, the infarct-related vessel was angiographically patent in 40 patients (41%). Vessel patency did not influence event-free survival, although a patent vessel, as compared with an occluded vessel, was associated with a greater prevalence of non-Q wave infarction (58 versus 21%, p less than 0.001), fewer persistent infarct zone thallium defects (1.2 +/- 1.1 versus 2.0 +/- 1.2, p = 0.001), more reversible infarct zone thallium defects (1.0 +/- 1.0 versus 0.5 +/- 0.9, p = 0.02) and a trend toward a higher left ventricular ejection fraction (53 +/- 10% versus 49 +/- 12%, p = 0.07). In summary, uncomplicated myocardial infarction in patients with single vessel coronary artery disease is associated with a very low incidence of subsequent death and reinfarction. The presence of infarct zone thallium redistribution, compared with its absence, is predictive of a higher cardiac event rate. These data should be considered when recommending prophylactic percutaneous transluminal angioplasty after uncomplicated myocardial infarction in asymptomatic patients with single vessel coronary disease. On the basis of these results, future randomized trials designed to evaluate the therapeutic efficacy of revascularization in asymptomatic postinfarction patients with single vessel disease should limit enrollment to those patients with residual ischemia located within the infarct zone. PMID- 3339162 TI - Clinical options in patients with single vessel coronary artery disease and acute myocardial infarction. PMID- 3339163 TI - Postmyocardial infarction pain and infarct extension in the coronary care unit: role of two-dimensional echocardiography. AB - Recent data suggest that patients who manifest extension of their acute myocardial infarct have a worse prognosis than to those who do not have this complication and, if identified early, may be candidates for more aggressive intervention. Serial two-dimensional echocardiography was used to diagnose myocardial infarct extension in 33 consecutive patients and its sensitivity was compared with that of electrocardiography (ECG) and serum creatine kinase determination. Infarct extension was diagnosed clinically using ECG and enzymatic criteria. The echocardiograms were scored using a weighted regional scoring system, with each segment of the left ventricle ascribed a percent of the total left ventricular mass. Abnormal regions were summed to yield a percent asynergy. In the postinfarction period, 19 episodes of acute ischemia occurred; in 9 of these episodes clinical extension was confirmed, and in 7 of the 9 episodes echocardiographic extension was detected. In the patients in whom infarct extension was documented clinically, the mean asynergy score increased from a mean of 19.2 +/- 11.3% to 36.1 +/- 18.2% (p less than 0.01). Where no extension was detected, the asynergy score improved from the initial 31.5 +/- 24.1% to 28.3 +/- 21.9% (p less than 0.05). The extent of the change in echocardiographic wall motion abnormality was not predicted by the amount of creatine kinase reelevation. Electrocardiography alone failed to distinguish which episodes of ischemia represented infarct extension and which did not. Greater degrees of asynergy were associated with worse in-hospital mortality. Two-dimensional echocardiography is a useful method for detecting myocardial infarct extension providing a means of assessing functional impact and prognosis. PMID- 3339164 TI - Mitral balloon valvuloplasty for mitral restenosis after surgical commissurotomy. AB - Mitral balloon valvuloplasty was performed in 14 patients with recurrent mitral stenosis 16.9 +/- 1.8 years (range 6 to 30) after surgical commissurotomy. There were 13 women and 1 man with a mean age of 55 +/- 4 years (range 23 to 73). Mitral balloon valvuloplasty resulted in an increase in mitral valve area from 0.8 +/- 0.1 to 1.7 +/- 0.2 cm2 (p = 0.001), a decrease in mean mitral diastolic pressure gradient from 15 +/- 2 to 7 +/- 1 mm Hg (p = 0.001) and an increase in cardiac output from 3.4 +/- 0.3 to 3.9 +/- 0.3 liters/min (p = 0.03). No deaths, strokes, vascular complications or conduction abnormalities were observed. Mitral regurgitation developed or increased in severity in seven patients (50%). There was no evidence of significant left to right shunt through the atrial septal puncture site after mitral balloon valvuloplasty. A good result (defined as a mitral valve area greater than 1.0 cm2, an increase in mitral valve area greater than 25% and a mean gradient less than 10 mm Hg) was achieved in 9 (64%) of the 14 patients. A subgroup of four patients who had a superior result (increase in mitral valve area of 1.7 +/- 0.2 versus 0.5 +/- 0.1 cm2 in the other 10 patients, p = 0.004) was identified. These patients had less echocardiographic evidence of rheumatic mitral valve damage and were the only patients who had sinus rhythm. They were also younger, less debilitated and had a lower grade of fluoroscopic valve calcification compared with the other patients. Thus, mitral balloon valvuloplasty is a safe and effective procedure for patients with recurrent mitral stenosis after surgical commissurotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339165 TI - Mitral regurgitation after percutaneous balloon mitral valvuloplasty in adults: evaluation by pulsed Doppler echocardiography. AB - Percutaneous balloon mitral valvuloplasty is a new technique used in the treatment of adult patients with mitral stenosis. To evaluate the occurrence and severity of mitral regurgitation after balloon valvuloplasty, 24 patients (20 women and 4 men, mean age 57 years) were studied using two-dimensional and Doppler echocardiography before and less than 24 h after this procedure. Mitral valve area increased after valvuloplasty in all patients, from 0.89 +/- 0.07 to 1.61 +/- 0.09 cm2 (p less than 0.001). Before valvuloplasty, 10 patients had no mitral regurgitation, 4 had 1+, 4 had 2+ and 6 had 3+ mitral regurgitation. After valvuloplasty, new mitral regurgitation occurred in six patients. Regurgitation grade did not change in 13 patients (54%), increased by one grade in 8 patients (33%) and by two grades in 3 patients (13%). Left atrial volume decreased in all except one patient from 100 +/- 12 to 83 +/- 12 cm3 (p less than 0.001). Neither age, sex, cardiac rhythm, initial mitral valve area, increase in mitral valve area, morphologic characteristics of the valvular and subvalvular apparatus, previous mitral commissurotomy nor effective balloon dilating area discriminated between those patients with and without an increase in mitral regurgitation after valvuloplasty. Thus, mitral balloon valvuloplasty is frequently associated with an increase in mitral regurgitation. However, in this series, no patient developed severe mitral regurgitation, and left atrial volume decreased in nearly all patients. An increase in mitral regurgitation could not be predicted from any features of the valve or subvalvular apparatus, clinical characteristics of the patients or technical aspects of the procedure. PMID- 3339167 TI - Differences between patients with ventricular tachycardia and ventricular fibrillation as assessed by signal-averaged electrocardiogram, radionuclide ventriculography and cardiac mapping. AB - This study examined 65 patients with ventricular tachycardia or fibrillation late after myocardial infarction to determine whether they differed with respect to duration of ventricular activation in sinus rhythm and left ventricular ejection fraction. Patients with spontaneous ventricular tachycardia had a longer ventricular activation time in sinus rhythm than did patients with spontaneous ventricular fibrillation. This difference was detected with the signal-averaged electrocardiogram (ECG) (tachycardia 181 +/- 33 ms, fibrillation 152 +/- 23 ms, p less than 0.001) and at epicardial mapping (tachycardia 210 +/- 17 ms, fibrillation 192 +/- 17 ms, p less than 0.02). Left ventricular ejection fraction was lower in patients with spontaneous ventricular tachycardia (0.22 +/- 0.09) than in patients with spontaneous ventricular fibrillation (0.27 +/- 0.09) (p less than 0.05). The patients with both spontaneous and inducible ventricular fibrillation had a shorter ventricular activation time on the signal-averaged ECG (129 +/- 17 ms) and a higher ejection fraction (0.36 +/- 0.05) than did either patients with spontaneous ventricular fibrillation and inducible ventricular tachycardia (158 +/- 21 ms and 0.25 +/- 0.08, respectively, each p less than 0.01) or patients with both spontaneous and inducible ventricular tachycardia (181 +/- 33 ms and 0.22 +/- 0.09, respectively, each p less than 0.001). Of the patients with inducible ventricular tachycardia, presentation with tachycardia rather than fibrillation was associated with a longer ventricular activation time on the signal-averaged ECG (181 +/- 33 versus 158 +/- 21 ms, p less than 0.02) and a longer cycle length of inducible ventricular tachycardia (290 +/- 61 versus 259 +/- 44 ms, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339168 TI - A comparative study of frequency domain and time domain analysis of signal averaged electrocardiograms in patients with ventricular tachycardia. AB - Although both time domain and frequency domain analysis of signal-averaged electrocardiograms (ECGs) may distinguish patients with and without sustained ventricular tachycardia, it remains unclear which method is superior. Both methods were assessed in 55 subjects comprising 26 patients with sustained ventricular tachycardia (Group I), 18 control patients with organic heart disease but without sustained ventricular tachycardia (Group II) and 11 normal volunteers (Group III). Time domain analysis was performed with high pass filtering of 25, 40 and 80 Hz and low pass filtering of 250 Hz. Frequency domain analysis was performed on the terminal 40 ms of the QRS complex, either alone or with 216 or 150 ms of the ST segment. Absolute summed energies of discrete frequency bands and band energy ratios were calculated. The effectiveness of discrimination between Groups I and II was evaluated in terms of group means, sensitivity, specificity and an information content index based on receiver operating characteristic curve analysis. Group I showed a uniform decrease in amplitude across all frequencies derived from the terminal 40 ms of the QRS complex (p less than 0.005). This was abolished by the inclusion of ST segment data in frequency domain analysis. No frequency band was unique for Group I. At a specificity of 78%, the best time domain sensitivity was 85%, and the best frequency domain sensitivity was 77%. The best time domain information content index was 0.156, the best index for frequency domain analysis was 0.077 using absolute band areas. It is concluded that patients with sustained ventricular tachycardia have decreased energy content across all frequencies in the terminal 40 ms of the QRS complex. Frequency domain analysis was not an improvement over time domain analysis in differentiating patients with ventricular tachycardia from those without. PMID- 3339166 TI - Parasympathetic and sympathetic alterations of Mobitz type II heart block. AB - This study examined the effects of changes in parasympathetic and sympathetic tone on the cycle length at which Mobitz type II second degree atrioventricular (AV) block occurred. Four patients who had electrocardiographic evidence of type II AV block and confirmation of block in the His-Purkinje system during electrophysiologic study were evaluated. These patients received intravenous atropine (1.0 to 2.4 mg), propranolol (0.15 mg/kg body weight) or isoproterenol (1 and 2 micrograms/min) alone or in combination. In two of three patients receiving propranolol, the atrial pacing cycle length at which 1:1 His-Purkinje conduction occurred was prolonged relative to control (from 360 to 470 ms and 440 to 590 ms, respectively). In contrast, atropine in the presence of beta adrenergic blockade shortened the cycle length at which 1:1 His-Purkinje conduction occurred in three of four patients receiving the drug (470 to 390, 630 to 570 and 590 to 560 ms, respectively). Isoproterenol also improved His-Purkinje conduction in the one patient receiving this drug. No agent affected the duration of the HV interval during spontaneous sinus rhythm or right atrial pacing. Thus, drugs that alter autonomic tone influence abnormal His-Purkinje conduction minimally during sinus rhythm but, importantly, may modulate the atrial pacing cycle length at which type II AV block occurs. PMID- 3339169 TI - Determination of left-sided pressure gradients by utilizing Doppler aortic and mitral regurgitant signals: validation by simultaneous dual catheter and Doppler studies. AB - Continuous wave Doppler echocardiography is an accurate and reproducible method for determination of intracardiac pressure gradients in stenotic valve lesions and right-sided regurgitant lesions. Twenty-three patients with either mitral or aortic regurgitation underwent simultaneous continuous wave Doppler and dual catheter pressure recordings to determine if instantaneous pressure gradients can be accurately determined by Doppler ultrasound in left-sided regurgitant valve lesions. Using the modified Bernoulli equation, the maximal and mean pressure gradients between the left ventricle and left atrium were determined by continuous wave Doppler ultrasound in patients with mitral regurgitation and compared with simultaneous catheter-derived pressures. The mean and end-diastolic pressure gradients between the aorta and left ventricle were determined by continuous wave Doppler ultrasound in patients with aortic regurgitation and compared with simultaneous catheter-derived pressures. Diastolic half-times by both continuous wave Doppler ultrasound and catheter pressures were compared in patients with aortic regurgitation. There was a linear correlation between the mean gradients in all patients (r = 0.94; SEE = 6 mm Hg) with a similar correlation between the instantaneous gradients (r = 0.98; SEE = 8 mm Hg). There was a linear correlation between diastolic half-times by catheter and Doppler ultrasound (r = 0.95; SEE = 39 ms). As with other valvular lesions, continuous wave Doppler echocardiography can be used in patients with mitral or aortic regurgitation to accurately determine intracardiac pressure gradients. PMID- 3339170 TI - Determinants of the relation between systolic pressure and duration of isovolumic relaxation in the right ventricle. AB - Previous studies have suggested that right ventricular systolic pressure can be predicted from noninvasive estimates of the interval between pulmonary valve closure and tricuspid valve opening. To determine the basis for this relation, phonocardiograms and high fidelity right atrial and ventricular pressures were recorded in 29 patients with a right ventricular systolic pressure ranging from 20 to 149 mm Hg. In 22 patients with normal right atrial pressure (less than or equal to 8 mm Hg), both the time interval and the magnitude of pressure decrease from pulmonary valve closure to tricuspid valve opening were linearly related to systolic pressure (r = 0.89 and 0.96, respectively). Early pulmonary valve closure (decreased "hang-out" time) contributed to the greater magnitude of isovolumic pressure decrease at high systolic pressures, but correction for hang out time did not eliminate the relation between systolic pressure and the pulmonary valve closure-tricuspid valve opening interval (n = 10). When patients with documented right coronary artery disease were excluded, the time constant for isovolumic pressure decrease also increased as a function of systolic pressure (r = 0.67, p less than 0.01, n = 24), suggesting impaired relaxation at high systolic pressures. However, the mean rate of pressure decrease (mean negative dP/dt) still was greater in patients with a high pressure because of the exponential nature of the isovolumic pressure-time relation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339171 TI - Comparison of ST segment depression in upright treadmill and supine bicycle exercise testing. AB - Significant differences in the hemodynamic response to upright and supine exercise have been reported in patients with coronary artery disease. The purpose of the present study was to compare the degree of myocardial ischemia as assessed by ST segment depression during upright treadmill and supine bicycle exercise in 98 patients with coronary artery disease and in 34 patients with normal coronary arteries. The amount of ST segment depression at maximal exercise in patients with coronary artery disease was 0.90 +/- 0.80 mm for treadmill and 1.34 +/- 1.09 mm for supine bicycle (p less than 0.001). The amount of ST segment depression during treadmill and supine bicycle exercise tests was also compared at highest similar heart rates (0.68 +/- 0.77 versus 1.17 +/- 1.01, p less than 0.001), at highest similar rate-pressure products (0.71 +/- 0.77 versus 1.08 +/- 1.04, p less than 0.001), at highest similar metabolic equivalents of oxygen consumption (MET) levels (0.69 +/- 0.75 versus 1.20 +/- 1.05 mm, p less than 0.001) and at the onset of angina (0.84 +/- 0.73 versus 1.18 +/- 0.88 mm, p less than 0.001). The rate-pressure product achieved at maximal exercise was similar in both tests (18.74 +/- 5.80 x 10(3) versus 18.81 +/- 5.17 x 10(3), p = NS). The occurrence of angina during treadmill and supine bicycle exercise tests was similar (47 of 98 versus 48 of 98, respectively, p = NS). For the detection of coronary artery disease, the sensitivity was 50.0% for treadmill and 63.3% for supine bicycle (p less than 0.05) and the specificity was 73.5 versus 70.6%, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339172 TI - Accuracy of Doppler echocardiography in quantification of left to right shunts in adult patients with atrial septal defect. AB - In previous experimental and pediatric studies, the ratio of pulmonary to systemic flow (Qp/Qs) was accurately estimated by Doppler echocardiography in various cardiac shunt lesions. The purpose of this study was to assess the accuracy of pulsed Doppler echocardiography in determining the magnitude of shunt flow in adult patients with an ostium secundum type atrial septal defect. In 32 patients with high quality echocardiograms and excellent Doppler signals, blood flow was measured in the right and left ventricular outflow tract by Doppler echocardiography. In 16 patients without heart disease, the correlation (r) between systemic (Qs) and pulmonary (Qp) blood flow was 0.96 (SEE = 0.417 liter/min, y = 1.05x - 0.21) and the mean Qp/Qs ratio was 1.01 +/- 0.09. In 16 patients with an atrial septal defect, the Qp/Qs ration measured by oximetry ranged from 1.34 to 4.61 and by pulsed Doppler echocardiography from 1.31 to 4.46 (p = NS). In these 16 patients, the correlation between the Qp/Qs ratio determined by oximetry and pulsed Doppler echocardiography was significant (r = 0.82, SEE = 0.54). In the total group of 32 patients, the correlation was stronger (r = 0.93, SEE = 0.37). Systematic differences between the invasive and noninvasive shunt calculations did not occur. Thus, in adult patients with an atrial septal defect of the secundum type and high quality echocardiograms, the magnitude of left to right shunt can be accurately assessed by pulsed Doppler echocardiography. In the absence of pulmonary hypertension, pulsed Doppler echocardiography provides precise information for the decision to undertake conservative or operative treatment. PMID- 3339173 TI - Doppler echocardiographic measurement of mitral flow volume: validation of a new method in adult patients. AB - Instantaneous intracardiac flow volumes can be calculated as the product of instantaneous flow velocity and instantaneous orifice area. This was accounted for in a new method of measuring stroke volume and cardiac output in the mitral orifice by pulsed Doppler echocardiography. This method was compared with simultaneous thermodilution in 30 adult patients in sinus rhythm without substantial atrioventricular or pulmonary valve abnormalities. The mitral orifice was assimilated to a conduit with 1) an ellipse-shaped inlet and outlet, 2) the same (and constant) long axis for the inlet and outlet ellipses (that is, the mediolateral anulus diameter measured on apical four chamber views), and 3) a varying outlet short axis (that is, the mitral anteroposterior leaflet separation derived from left parasternal M-mode recordings). This method design avoided the need for a short-axis view of the whole circumference of the mitral outlet orifice, which is difficult to obtain in many adult patients. The mitral flow velocity was recorded from the apex under two-dimensional guidance, within the mitral canal, close to the outlet section. Integration of instantaneous mitral leaflet separation multiplied by instantaneous flow velocity was performed using Simpson's rule. In addition to the proposed "instantaneous orifice area" method (method A), a "mean orifice area" method (method B) was also compared with thermodilution. In this simplified method, mitral flow was the product of mean orifice area and the diastolic mitral velocity integral, both derived from the same recordings as for method A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339174 TI - Use of procainamide with rapid atrial pacing for successful conversion of atrial flutter to sinus rhythm. AB - Rapid atrial pacing is a useful technique and often the therapy of choice to terminate atrial flutter in patients. However, interruption of atrial flutter by rapid atrial pacing may not always produce sinus rhythm, but rather may result in atrial fibrillation. Twelve patients with spontaneous atrial flutter that had been present for greater than 24 h were studied to assess the efficacy of atrial pacing, alone and in combination with procainamide, to convert atrial flutter to normal sinus rhythm. Rapid atrial pacing for greater than or equal to 15 s from selected atrial sites at selected pacing rates were performed during atrial flutter. The initial pacing rate was always at a cycle length 10 ms shorter than the atrial flutter cycle length. If atrial flutter persisted after cessation of pacing, it was repeated at progressively shorter cycle lengths until either a rate of 400 beats/min was achieved or atrial fibrillation was induced. In two patients, atrial flutter was converted to sinus rhythm with pacing alone. Three patients developed sustained atrial fibrillation as a result of the rapid atrial pacing, this rhythm ultimately reverting back to atrial flutter in two. Ten patients received procainamide and 9 of the 10 had lengthening of the atrial flutter cycle length by a mean of 68 ms (1 patient continued to have atrial fibrillation). Then, using the same atrial pacing protocol, high right atrial pacing alone at a mean cycle length of 227 ms interrupted atrial flutter in all these patients, returning their rhythm to sinus rhythm. It is concluded that intravenous procainamide effectively augments the efficacy of rapid atrial pacing to convert atrial flutter to sinus rhythm. PMID- 3339175 TI - Comparison of defibrillation efficacy in humans using a new catheter and superior vena cava spring-left ventricular patch electrodes. AB - The automatic implantable cardioverter-defibrillator currently utilizes an electrode system that requires a major operation for implantation. Effective defibrillation using an implantable cardioverter-defibrillator catheter positioned transvenously would eliminate the morbidity associated with such surgery. Fifteen patients undergoing defibrillator implantation were studied to compare the efficacy of the catheter with that of the superior vena cava spring (6.7 cm2, anode)-left ventricular patch (13.5 cm2, cathode) electrode system using truncated exponential waveforms with 60% tilt. The catheter is 11F in diameter and tripolar. A distal platinum-iridium tip used for pacing was separated by 4 mm from a middle 4.3 cm2 platinum electrode; these were positioned at the right ventricular apex. The proximal 8.5 cm2 platinum electrode was situated at the superior vena cava-right atrial junction. Defibrillation was performed using the middle (cathode) and proximal (anode) electrodes. Ventricular fibrillation was induced by alternating current six times, and defibrillation shocks of 1, 5, 10, 15, 20 or 25 J were given in random order, first using the catheter and then the spring-patch system. Rescue shocks of higher energy were given if there was failure. Although very low energy levels appeared to be slightly more efficacious when using the spring-patch system, there was no statistically significant difference between the electrode systems for any of the energies tested. Permanent implantation of the catheter would have been suitable in 45% of the patients, as compared with 54% of patients with the spring-patch system (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339176 TI - Transvenous catheter defibrillation for prevention of sudden cardiac death. PMID- 3339177 TI - Are routine preoperative cardiac catheterization and angiography necessary before repair of ostium primum atrial septal defect? AB - Two-dimensional and Doppler echocardiography were compared with cardiac catheterization and angiography in the preoperative evaluation of ostium primum atrial septal defect. Preoperative echocardiographic examinations as well as operative reports of all patients (33 patients aged 2 months to 23 years at surgery) with ostium primum atrial septal defect or transitional atrioventricular (AV) canal defect having had echocardiography and surgical repair at The Children's Hospital, Boston from July 1983 to January 1986 were retrospectively reviewed. Original cardiac catheterization and angiographic reports also were reviewed. Preoperative echocardiography resulted in no false positive or false negative primary diagnoses when compared with the diagnoses obtained at preoperative angiography or surgery. Doppler assessment of mitral regurgitation correlated well with angiographic (93% agreement) and intraoperative (85% agreement) assessments of mitral regurgitation to within two diagnostic categories on the six level scoring system used. There was reasonably good agreement between the two-dimensional echocardiographic estimate of right ventricular systolic pressure and that measured at catheterization when expressed as percent of the simultaneous left ventricular pressure. Seven of nine ventricular septal defects observed intraoperatively were noted on preoperative echocardiography; five of these defects were detected on preoperative angiography. A variety of other surgically confirmed associated cardiovascular defects were observed by both preoperative techniques. However, echocardiography appeared to be superior to angiography for evaluation of AV valve morphology and papillary muscle architecture. This study implies that in children with typical clinical and two-dimensional echocardiographic and Doppler findings for ostium primum atrial septal defect or transitional AV canal defect, routine preoperative cardiac catheterization and angiography are unnecessary. PMID- 3339178 TI - Ectopic automatic atrial tachycardia in children: clinical characteristics, management and follow-up. AB - Ectopic automatic atrial tachycardia, an uncommon type of supraventricular tachycardia in children and adults, has been reported to be resistant to medical therapy, and surgical or cryoblation has been recommended. This report describes 10 infants and children (median age 6 months; range birth to 7.5 years) with automatic atrial tachycardia and their management and follow-up. Digoxin alone was unsuccessful in controlling tachycardia in all 10 patients but decreased the tachycardia rate by 5 to 20% in 8. Intravenous (0.1 mg/kg body weight per dose) and oral propranolol successfully suppressed tachycardia in three of five patients and oral propranolol successfully controlled tachycardia in two of five other patients. Class I antiarrhythmic agents--quinidine (three patients), procainamide (four patients) and phenytoin (three patients)--did not control tachycardia in any patients but made the tachycardia rate worse in three patients. Intravenous (5 mg/kg per dose) and oral amiodarone suppressed tachycardia in three of four patients and oral amiodarone suppressed it in another patient. Thus, intravenous propranolol and amiodarone were effective in acutely suppressing automatic ectopic atrial tachycardia and predicted the response to long-term oral therapy. One patient had persistent tachycardia after surgical ablation of the high right atrial ectopic focus, and another patient had unsuccessful catheter ablation of the high right atrial ectopic focus (25 J). During follow-up (10 to 28 months), ectopic atrial tachycardia resolved completely in four patients and was well controlled in four patients. PMID- 3339179 TI - Tetralogy of Fallot with obstruction of the ventricular septal defect: spectrum of echocardiographic findings. AB - Tetralogy of Fallot with a restrictive ventricular septal defect and suprasystemic right ventricular pressure is an uncommon anomaly with a high mortality rate. In previous studies, the identity of the tissue obstructing the ventricular septal defect has usually not been determined preoperatively. This report describes the echocardiographic and anatomic features in 4 patients with a restrictive ventricular septal defect among 269 patients with tetralogy of Fallot undergoing surgical repair. Echocardiography determined the presence and identity of the obstructing tissue in all four patients. In one patient, the defect was small in association with marked septal hypertrophy. In three patients, accessory or excessive tricuspid valve tissue obstructed the defect in a manner similar to spontaneous closure of isolated membranous ventricular septal defects. Autopsy and catheterization findings are also presented of an additional case with a unique mechanism of obstruction by a tricuspid valve with Ebstein's anomaly. In patients with tetralogy of Fallot, recognition of an obstructed ventricular septal defect is important because it appears to have a poor prognosis. PMID- 3339180 TI - Pulmonary artery origin of the left coronary artery: diagnosis by two-dimensional echocardiography, pulsed Doppler ultrasound and color flow mapping. AB - Five children, aged 0.2 to 6.7 years, with pulmonary artery origin of the left coronary artery proved by angiography underwent echocardiographic examination from 1985 through 1986. Prospective identification of this condition was achieved by two-dimensional echocardiography alone in two patients. Using a parasagittal plane from the second or third intercostal space, identification of the anomalous origin from the pulmonary artery was also possible in the other children on subsequent examination. In all of these studies the right coronary artery was considerably enlarged. The ratio of the diameters of the right coronary artery and the aortic root was 0.25 to 0.33 (normal 0.12 +/- 0.02). Flow mapping by color Doppler ultrasound in three children studied most recently and peripheral arterial or aortic root contrast echocardiography identified the site of entry of the coronary flow into the pulmonary artery. The flow disturbance was detected on the aortic surface of the pulmonary artery opposite the portion from where the flow from a patent ductus is usually identified. Pulsed Doppler ultrasound identified the flow disturbance in the pulmonary artery in only three of the children. The two youngest patients did not demonstrate turbulence on pulsed Doppler ultrasound, but they were not examined by color Doppler ultrasound. The accuracy of noninvasive detection of pulmonary artery origin of the left coronary artery by ultrasound is improved by the use of a combined echocardiographic approach. PMID- 3339182 TI - Effect of transmural versus nontransmural myocardial infarction on inducibility of ventricular arrhythmias during sympathetic stimulation in dogs. AB - Transmural myocardial infarction interrupts sympathetic nerves and denervates viable muscle distal to myocardial infarction. The effect of sympathetic stimulation on responses to programmed ventricular stimulation was studied in dogs without myocardial infarction (Group I: n = 5), with transmural anterior wall myocardial infarction (Group II: n = 6) and with nontransmural anterior wall myocardial infarction (Group III: n = 9). Ventricular effective refractory period during sympathetic stimulation decreased by 16 +/- 18, 1 +/- 2 and 12 +/- 8 ms (mean +/- SD) in viable muscle of the inferoapical left ventricle in Groups I, II and III, respectively, suggesting efferent sympathetic denervation by transmural myocardial infarction only. Sustained ventricular tachycardia or fibrillation was induced more easily during sympathetic stimulation in six of the six dogs with transmural infarction, but in only two of the nine dogs with nontransmural infarction (p less than 0.01). It is concluded that the partial sympathetic denervation produced by transmural myocardial infarction enhances the ease of induction of ventricular tachycardia and fibrillation during sympathetic stimulation. A similar mechanism may lead to increased risk for lethal arrhythmias during periods of high sympathetic tone in patients with transmural myocardial infarction. PMID- 3339181 TI - Differential effects of procainamide, lidocaine and acetylstrophanthidin on body surface potentials and epicardial conduction in dogs with chronic myocardial infarction. AB - Twenty-eight anesthetized mongrel dogs were studied 2 to 74 months after experimental myocardial infarction in order to examine the effects of procainamide, lidocaine and acetylstrophanthidin on conduction within the infarcted region and the way such effects relate to changes in body surface potentials and antiarrhythmic efficacy. In each animal, 100 to 200 QRS complexes in the X, Y, Z leads were signal averaged, vector summed and high pass filtered at 50 Hz. Susceptibility to ventricular arrhythmia was evaluated using routine programmed ventricular extrastimulation in the anesthetized open chest animal. Epicardial electrograms were sequentially recorded at 45 standard sites within the infarcted region and referenced to the beginning of the QRS complex. Of the three agents, only procainamide exhibited antiarrhythmic action whereas lidocaine and acetylstrophanthidin produced inconsistent effects. Procainamide prolonged the time at which activity in the epicardial electrographic recordings ended relative to the beginning of the body surface QRS complex. This effect was significantly greater in electrograms that ended late in the QRS complex in the control state than for those that ended earlier. Such preferential effect on more abnormal sites was reflected on the body surface as a greater effect of procainamide in prolonging the lower energy terminal portion of the signal averaged QRS complex than the earlier high energy portion. In contrast, lidocaine significantly prolonged the time at which electrograms ended only for those relatively normal electrograms that ended early in the QRS complex in the control state. In the signal-averaged body surface QRS complex, lidocaine produced a small but significant prolongation of the early high energy portion of the QRS complex but no change in the late portion. Acetylstrophanthidin produced a significant prolongation in early-ending electrograms and, surprisingly, significantly shortened the end time of electrograms that ended late in the QRS complex in the control state. Such effects were not reflected, however, on the body surface because acetylstrophanthidin had no significant effect on either the early or the late portion of the QRS complex. It is concluded that procainamide's differential effect between early- and late-ending electrograms is detected on the body surface by a greater prolongation in the terminal portion of the QRS complex. The signal-averaged body surface QRS complex is less sensitive in detecting the more subtle effects on conduction caused by lidocaine and acetylstrophanthidin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3339184 TI - Effects of clofilium on ischemic subendocardial Purkinje fibers 1 day postinfarction. AB - One day after ligation of the canine anterior descending coronary artery, clofilium, a long-acting class III antiarrhythmic agent, was studied for its effects on normal and ischemic Purkinje fibers. In normal Tyrode's solution (4 mM potassium, 2.7 mM calcium) clofilium (10(-7) to 10(-5) M) increased action potential duration. Although only 2 of 10 normal Purkinje fibers developed early after depolarizations and early afterdepolarization-initiated triggered activity, 10 of 11 ischemic Purkinje fibers developed these features. Consequently, action potentials in ischemic fibers were prolonged to durations greater than 10 s. The triggered activity in the ischemic Purkinje fibers produced repetitive activity in adjacent normal ventricular muscle. In vivo, 3 days after ligation, the administration of 3 to 10 mg/kg clofilium induced grouped beating. Action potentials recorded subsequently from these same hearts in vitro showed early afterdepolarizations, triggered activity and a similar grouping of responses. Therefore, clofilium differentially produced early afterdepolarizations in ischemic Purkinje fibers. This is a mechanism by which clofilium could be arrhythmogenic in an ischemic heart. PMID- 3339186 TI - Abstracts. 37th annual scientific session, American College of Cardiology, Atlanta, Georgia, March 27-31, 1988. PMID- 3339185 TI - Synthetic quality of some analytic quantities. PMID- 3339183 TI - Extracellular potassium dynamics in the border zone during acute myocardial ischemia in a canine model. AB - Bifunctional intramyocardial potassium ion (K+)-sensitive and bipolar wire electrodes were used to evaluate extracellular K+ dynamics and electrophysiologic changes during acute myocardial ischemia in the border zone, ischemic zone (5 to 7 mm from the border), central ischemic zone (15 to 25 mm from the border) and normal myocardium in 11 open chest dogs during a 30 min ligation of the left anterior descending coronary artery. At the end of this period, the hearts were injected with rhodamine dye and quickly frozen. Ultraviolet NADH (nicotinamide adenine dinucleotide) rhodamine fluorescence photography was used to localize the border between normally perfused and ischemic tissue and determine the site of electrodes in relation to this border. Before coronary ligation, extracellular K+ ranged from 4.0 +/- 0.3 to 4.3 +/- 0.3 mM in these four zones. After ligation, extracellular K+ accumulated in the ischemic and central ischemic zones in a pattern characterized by an initial rapid increase for approximately 5 min, followed by a slowly rising plateau phase, reaching maximal levels of 9.8 +/- 2.0 and 14.4 +/- 4.4 mM, respectively. In contrast, K+ dynamics in the border zone showed a biphasic response, with an initial rapid increase to a maximal level of 7.5 +/- 2.4 mM at approximately 9 min after coronary ligation, followed by a gradual decrease to a level of 5.3 +/- 1.2 mM by the end of the 30 min ligation period. No significant changes in K+ occurred in the normal zone throughout the ischemic period. The correlation of K+ electrode, electrophysiologic and postmortem NADH-rhodamine fluorescence data indicated the existence of a well defined border zone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339188 TI - The American Academy of Allergy and Immunology. Forty-fourth annual meeting. March 11-16, 1988, Anaheim, California. Abstracts. PMID- 3339187 TI - Circulating concentrations of histamine, neutrophil chemotactic activity, and catecholamines during the refractory period in exercise-induced asthma. AB - Circulating mediators and catecholamine concentrations have been measured in eight subjects with asthma who were subjected to two bouts of cycle ergometer exercise separated by 1 hour. The maximum falls in FEV1 were 21.9 +/- 2.3% (mean +/- SEM; n = 8) and 5.5 +/- 1.3% (mean +/- SEM; n = 8) after the first and second exercises, respectively. Serum neutrophil chemotactic activity (NCA) and plasma histamine and catecholamine levels in venous blood were measured with a microchemotaxis and two radioenzymatic techniques, respectively. There was a significant increase in NCA and plasma histamine concentrations after both exercise challenges, and there was no significant difference in the release of these mediators between the two exercise tests. Gel filtration chromatography demonstrated that the NCA detected after the first and second exercise tests had molecular sizes of approximately 600,000 daltons. There was no significant time dependent increase in plasma norepinephrine and epinephrine concentrations after either exercise task, even though the patients were refractory to exercise induced asthma after the second exercise. These results suggest that the refractory period in exercise-induced asthma is not caused by mediator depletion, as indicated by NCA and histamine measurements, or by protection of the airways through catecholamine release. PMID- 3339189 TI - Probit analysis applied to the allergen dose-response curve: a method for epidemiologic surveys. AB - The degree of skin sensitivity to five common allergens (grass, Dermatophagoides pteronyssinus, mugwort, birch, and Parietaria) was determined by the threshold dilution technique in all the skin test reactors of a random sample of 295 schoolchildren (142 male and 153 female subjects, age range 11 to 14 years), and the frequency distribution of responders at each concentration was analyzed by probit analysis. The potency of each allergen was presented in terms of median effective dose (ED50), and comparison between different allergens and between symptomatic and asymptomatic subjects was made by computing the relative potency. The ED50 of the allergens was found to be nearly identical (grass, 13.5; D. pteronyssinus, 12.3; mugwort, 9.6 activity units by RAST (AUR)/ml) with the exception of birch (22 AUR/ml). Grass and D. pteronyssinus demonstrated a lower ED50 in symptomatic subjects (3.3 and 2.8 AUR/ml, respectively) than in asymptomatic subjects (85 and 27 AUR/ml, respectively). The lower fiducial limits of ED50 in symptomatic subjects demonstrated to be a cutoff point, since they included only 5% and 12% of asymptomatic reactors to grass and D. pteronyssinus, respectively. We conclude that probit analysis applied to the distribution of threshold doses of allergen extracts is a useful method to evaluate skin sensitivity in epidemiologic surveys. We believe that the ED50 is a practical and reliable allergy index. PMID- 3339190 TI - Fatal varicella in steroid-dependent asthma. AB - Disseminated varicella infection is a potentially life-threatening complication of chronic high-dose corticosteroid (CS) or immunosuppressive therapy. A review of the literature indicates that, with one possible exception, this complication has not occurred in a CS-dependent subject with asthma. We present in this article the clinical features and autopsy findings of a steroid-dependent subject with asthma who died of acute, disseminated varicella. A 16-year-old poorly compliant, steroid-dependent subject with asthma received two courses of high dose intravenous methylprednisolone during a 3-week period, followed by a tapering schedule of oral prednisone. During this time, she was exposed to chickenpox. She subsequently developed a classic varicella rash, sever back pain, rapidly progressive hepatic failure, pneumonitis, and encephalopathy. Death ensued 3 days after the onset of the rash. Evidence of disseminated varicella infection was confirmed at autopsy. This case illustrates that a small number of subjects with severe asthma receiving high-dose CS need to be considered as a separate, high-risk group for developing disseminated varicella. We recommend that the immune status of these patients to varicella-zoster virus be assessed by a serum titer. If these patients are nonimmune, they would be candidates for varicella-zoster immune globulin on exposure, and for acyclovir therapy should varicella dissemination occur. PMID- 3339191 TI - Circadian and circannual rhythms of allergic rhinitis: an epidemiologic study involving chronobiologic methods. AB - Seven hundred sixty-five patients, living in France and suffering from allergic rhinitis (eg, with positive skin tests to various antigens), agreed to self-rate (visual analog scales), four times daily, symptoms such as sneezing, stuffy or blocked nose, runny nose, itchy nose, itchy eyes, wheeze, or cough. Despite acute symptoms, patients did not take medications of any kind by any route during 36 hours. Several statistical methods (eg, Student's t test, analysis of variance, cosinor, chi-square, etc.) were used to validate both circadian and circannual rhythms of these symptoms in the group as a whole, as well as in subgroups related to age, sex, etc. Large-amplitude circadian rhythms with early morning peak times (eg, approximately 6 AM) were validated for sneezing, stuffy nose, and runny nose (with p less than 0.0001) but not for wheeze or cough. Such time dependent changes were related neither to age (from 10 to 80 years) nor to sex. However, small differences were observed in subgroups sorted with regard to duration of disease (old versus new cases), smoking habits, and geographic location (north versus south France). Reanalysis of data taking into account interindividual differences revealed that the respective peak times of the three major symptoms occurred in the early morning in about 60% to 70% of the patients. Annual changes were validated as well with the annual peak time being January to April. The proposed interpretation of both circadian and circannual rhythms suggests taking into account endogenous component rhythms (eg, involving metabolic, immunologic, and endocrine systems), since they contribute to time dependent changes in the human susceptibility to antigens. In addition, the elevated severity of symptoms in the morning experienced by 60% to 70% of patients should serve as a guide to individually optimize dosing time(s) of medications, such as antihistamines. PMID- 3339192 TI - Allergy in asthma. I. The dose relationship of allergy to severity of childhood asthma. AB - The relationship between allergy and childhood asthma was investigated. We hypothesized that if allergy were a factor in aggravating asthma, we should find that allergy (defined by symptoms and numbers of positive prick skin tests) increased with increasing severity of asthma. One hundred forty-two children with asthma, referred to a pulmonologist and an allergist, 123 of whom were skin tested, were graded according to clinical severity and compared to a group of 29 normal individuals, 48 patients with allergic rhinitis, and 52 patients with cystic fibrosis. The 29 symptom-free individuals had only one positive skin test among them, whereas 65% of the clinic patients with asthma had three or more positive skin tests (p less than 0.001). This compared with 35.4% of the patients with rhinitis (p less than 0.001) and 14% of the patients with cystic fibrosis (p less than 0.001). There was an increase in the number and size of positive skin tests with increasing severity of asthma. Similarly, there was increased reporting of allergic symptoms, such as sensitivity to animals with increasing severity of asthma. These data indicate that atopy is associated with asthma in a crude dose-response fashion, and children with chronic, steroid-dependent asthma are often highly atopic, easily sensitized, and form IgE antibodies to a broad range of allergens. PMID- 3339193 TI - Allergy in asthma. II. The highly atopic infant and chronic asthma. AB - The relationship between allergy and asthma in infants and preschool children was investigated. One hundred nine children, median age 2 1/2 years, were examined immunologically by quantitation of serum IgE, RAST testing to 13 allergens, and culture of peripheral blood lymphocytes for spontaneous IgE formation. We examined a cross-section of infants and toddlers to determine whether the severity of asthma is associated with allergy as has been reported in older children with asthma. We identified a group of highly atopic infants and preschool children who have serum IgE at least 10 times the mean + 1 SE for age, multiple positive RASTs with early formation of IgE to inhalant antigens, and circulating B cells that spontaneously form IgE when these are cultured in vitro. Such highly atopic infants and preschool children were statistically more likely to have chronic asthma requiring multiple continuous medication compared to the rest of the population (p less than 0.01). PMID- 3339195 TI - Occupational asthma from reactivity to an alkaline hydrolysis derivative of gluten. AB - A 29-year-old female subject had been working for 13 years in a company producing biscuits. She was exposed intermittently to an alkaline hydrolysis wheat gluten derivative (AHGD) that was incorporated into marshmallows. Five years before being referred, she started reporting rhinoconjunctivitis and asthmatic symptoms immediately after handling AHGD. When she was first assessed, she had avoided contact with AHGD for 1 year, and she was asymptomatic. Normal spirometry and bronchial responsiveness to histamine (provocative concentration causing a 20% fall in FEV1, 22 mg/ml) were obtained. There was a positive allergy skin test to ragweed pollen and to AHGD at 0.01 mg/ml. Skin tests with individual extracts of cereals, including wheat, were negative. Inhalation challenge with AHGD for 15 seconds caused immediate rhinoconjunctivitis and bronchoconstriction (maximum fall of 40% in FEV1 30 minutes after the exposure) with complete recovery 2 hours later. There was no reaction thereafter, and the provocative concentration of histamine causing a 20% fall in FEV1 was not significantly changed (13.1 mg/ml) 9 hours after the challenge. Inhalation challenge with wheat flour containing native gluten for 30 minutes did not cause any symptoms or significant change in FEV1. IgE RAST counts were greater with the AHGD than with gluten and the whole wheat extract; the opposite was generally found with sera from individuals with baker's asthma and wheat food allergy. With the serum of the affected worker, AHGD completely inhibited the corresponding RAST, but gluten did not. With wheat food allergy, AHGD was relatively inactive inhibition of the wheat and gluten RAST, but gluten was effective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339194 TI - A study of the prevalence and clinical significance of venom-specific IgE. AB - The prevalence of unrecognized Hymenoptera-venom sensitization, assessed by venom skin tests (VSTs) in adults with no history of adverse reactions to sting, has been as high as 12% in previous epidemiologic studies. To assess further the clinical importance of positive VSTs in such individuals, we skin tested 33 subjects stung in the field during the preceding 12 months without reaction, and 33 persons who denied being stung in the preceding 3 years. Among the recently stung group, 12/33 had at least one positive VST (greater than or equal to 2+) at 1.0 microgram/ml, whereas 5/33 had positive VST at 0.1 microgram/ml. In contrast, only 2/33 nonstung subjects had positive VST at 1.0 microgram/ml, and none were positive at 0.1 microgram/ml. To estimate, prospectively, the sensitization rate after insect stings, we studied a third group of 11 nonsensitive patients with negative skin tests to Hymenoptera. After a deliberate in-hospital honeybee sting, only 1/11 developed a persistently positive honeybee VST. From among the three groups, we then performed nine sting challenges in eight patients with positive VSTs, and all stings were tolerated without significant reaction. We also measured IgE antibodies to Hymenoptera venoms in random blood bank donors. During April to May, 2/216 sera contained elevated venom-specific IgE antibodies, whereas 14/201 sera collected from October to November contained elevated venom specific IgE antibodies. We conclude that a small but appreciable portion of the population has venom-specific IgE antibodies and that the prevalence is seasonably variable. Our data indicate that persons recently stung without significant reaction contribute to this group but that only a small portion of this group is at risk for a systemic reaction with a future sting. PMID- 3339196 TI - Experimental hypersensitivity pneumonitis in the mouse: histologic and immunologic features and their modulation with cyclosporin A. AB - A murine model of hypersensitivity pneumonitis (HP) was established with transnasally administered Thermoactinomyces vulgaris (Tv) bacilli. Bronchoalveolar lavage (BAL) of experimental animals revealed marked increase in the total cell, lymphocyte, and macrophage numbers; the findings were similar to those in human HP. The BAL lymphocytes were mostly Thy 1.2 positive. Lyt-1 positive cells predominated Lyt-2 positive cells. Anti-Tv IgG antibodies and delayed-type hypersensitivity footpad reactions against Tv were detected in animals with HP. Cyclosporin A (CyA), a potent immunosuppressive drug, had marked effects on the development of HP in this model. When CyA was administered throughout the course of Tv inoculations, the granulomatous pneumonitis was markedly suppressed, and an increase in BAL lymphocytes, Thy 1.2 positive cells, was suppressed. When CyA was administered only during the first half period of the Tv treatment, suppression of the disease was minimal; when CyA was administered in the latter half, both the HP lesions and the increase in BAL cell lymphocyte numbers were significantly suppressed. These results indicate that a series of transnasal administration of Tv in mice may provide a good model for human HP. PMID- 3339197 TI - Oropharyngeal candidiasis in patients treated with beclomethasone dipropionate delivered by metered-dose inhaler alone and with Aerochamber. AB - We compared the incidence of Candida infection, Candida colonization, and reduction in oral prednisone dose in patients with asthma treated with beclomethasone dipropionate delivered by metered-dose inhaler (MDI) alone and MDI plus Aerochamber. Group M contained 18 patients treated with beclomethasone, four actuations four times a day (672 micrograms/day), delivered by MDI alone. Group A contained 18 patients treated with the same dose of beclomethasone delivered by MDI plus Aerochamber. In group M, four of 18 patients had Candida infection, 12 of 18 patients had Candida colonization, and six of 18 patients were completely removed from oral prednisone. In group A, 0 of 18 patients had Candida infection (p = 0.05), six of 18 patients had Candida colonization (p less than 0.05), and 12 of 18 patients were completely removed from oral prednisone (p less than 0.05). We conclude that beclomethasone delivered by MDI plus Aerochamber is more efficacious in reducing oral prednisone dependency and produces less Candida infection and colonization than beclomethasone delivered by MDI alone. PMID- 3339198 TI - Occupational allergy to avian proteins presenting as allergy to ingestion of egg yolk. PMID- 3339200 TI - National Nutrition Month, 1988. PMID- 3339199 TI - Comparison of parallel line skin test assay (PLST) and ELISA inhibition (EI) methods for determination of relative potency of polymerized grass and ragweed antigenic extracts. AB - Relative potency estimates were performed by parallel line skin test assay (PLST) and ELISA inhibition methods for three polymerized allergen extracts (Bermuda grass, orchard grass, and a copolymer of short and giant ragweed) versus four unmodified RAST standardized reference extracts (Bermuda grass, orchard grass, and giant and short ragweed) in nine subjects. One subject experienced a systemic reaction, requiring treatment at the end of the PLST assay. Another subject had a systemic reaction during limited skin testing performed approximately 72 hours after completion of PLST. Relative potency values for the polymerized extracts obtained by PLST were much lower than those obtained by ELISA inhibition, but results were significantly (r = 0.95; p less than 0.01) correlated. Because polymerized allergen extracts are designed to be hypoallergenic, a skin test assay may underestimate their potency relative to an unmodified reference extract. PMID- 3339201 TI - Meeting the demands of the National Cholesterol Education Program: some ideas from the field. PMID- 3339202 TI - Acceptability of a 7-day higher-carbohydrate, lower-fat menu: the Beltsville Diet study. AB - For 13 weeks, 20 men (aged 23 to 56), 19 premenopausal (aged 21 to 48), and 14 postmenopausal women (aged 49 to 65) consumed a 7-day rotation menu conforming to dietary recommendations of several research and health organizations. The diets were designed to make minimal changes in the standard American diet by the use of well-accepted normal foods. The average daily composition of the diet was 50% carbohydrate (complex 35%, simple 15%), 35% fat (P:S 0.7), and 15% protein; it contained 100 mg cholesterol, 1 gm sodium, and 14.5 gm neutral detergent fiber per 1,000 kcal. The acceptability of the menus was examined through questionnaires administered after the experimental diet period. Subjects rated the menus and individual foods and made recommendations for improvement of the menus. Most subjects (33 of 41 responding) rated the menu better than or almost as good as their usual diet. Few (9) were ever hungry during the 13-week period. During the study, a number of biochemical parameters were measured; the measurements indicated beneficial results. Blood pressure, cholesterol levels, and glucose responses were all improved after consumption of the menu. The results indicate that with minimal changes in the normal U.S. diet, acceptable menus that have beneficial effects on risk factors for heart disease and diabetes can be developed. PMID- 3339204 TI - Trends in fatty acid intakes of 10-year-old children, 1973 to 1982. AB - Diets of four groups of 10-year-old children (no. = 871, 30% black, 70% white) were examined over 10 years with 24-hour dietary recalls to study temporal trends in cholesterol, fat, and fatty acid intakes in a community. Boys had higher intakes per day and per kilogram body weight than girls for all nutrients (p less than .0001), but there were no sex differences in nutrients per 1,000 kcal. The only racial difference detected was a higher myristic acid intake in whites (p less than .02). There was a 16% decline in dietary cholesterol intake between 1978 and 1982. Three shifts in fatty acid intake increased the P:S ratio from 0.29 in 1973 to 0.45 in 1978: (a) a 5% decline in oleic acid, coupled with a 5% rise in linoleic acid; (b) a quadrupling of linolenic acid; and (c) less stearic and more myristic acid, with palmitic acid unchanged. Total fat intake provided 38% of the calories in each survey, but the changes in proportions of fatty acids paralleled trends in food consumption patterns and nutrient sources. Despite the changes, few children met prudent diet recommendations, and serum total cholesterol and very-low-density-lipoprotein cholesterol levels did not change over time. PMID- 3339203 TI - A saturated fat/cholesterol avoidance scale: sex and ethnic differences in a biethnic population. AB - Avoidance of saturated fat and cholesterol by 1,210 Mexican Americans and 866 non Hispanic whites was assessed as part of a population-based survey of diabetes and cardiovascular risk factors. Participants ranged in age from 25 to 64 years and resided in three socioeconomically distinct neighborhoods of San Antonio, TX: low income, middle income, and upper income. A scale was constructed to assess the degree to which individuals avoided six dietary sources of saturated fat and cholesterol. Women of both ethnic groups were found to avoid saturated fat and cholesterol to a greater degree than men, scoring higher on five of the six components of the scale. Saturated fat/cholesterol avoidance increased significantly with increased socioeconomic status in both ethnic groups. Although there were no ethnic differences in overall saturated fat/cholesterol avoidance, more non-Hispanic whites recognized milk, eggs, and visible fat on meat as food sources to avoid. The scale described in this paper provides useful information about the specific food components recognized as dietary sources of saturated fat and cholesterol and helps identify those population groups that would benefit from nutrition education programs. Because of its simplicity and ease of administration, the scale may be a useful tool in epidemiological research. PMID- 3339205 TI - Evaluation study of the California Expanded Food and Nutrition Education Program: 24-hour food recall data. AB - The California Expanded Food and Nutrition Education program (EFNEP) Evaluation Study evaluated the effectiveness of the California program. The eating habits of 683 persons were studied in a group receiving EFNEP instruction (355 participants) and a control group (328 participants) that received no instruction. The 24-hour food recall was used to assess eating habits using the Synectics method. At the beginning of the study, there were no differences in food recall scores between the EFNEP and the control groups. After 6 months of instruction in the EFNEP group, there was a significant increase in food recall score for that group and no change in the control group. The improvements observed in the EFNEP group resulted from increased intakes from the milk, protein, and fruit and vegetable food groups. The program characteristics that led to those changes were determined to be in the length of the EFNEP visit, the number of EFNEP visits, and the EFNEP instruction topics. These results show that the California EFNEP is effective in producing significant changes in the eating habits of the low-income individuals it serves. PMID- 3339206 TI - Lean meats make the grade--a collaborative nutrition intervention program. AB - Lean Meats Make the Grade is a collaborative nutrition intervention program involving the Minnesota Heart Health Program (MHHP), the Minnesota Beef Council, and the Pork Producers Council. The purposes of this program were to educate consumers about identification of leaner cuts of meat, low-fat preparation methods, and selection of appropriate meat portion size. Program components included training for meat managers, taste testing for consumers, recipes and customer information brochures, and labels on individual meat packages to assist in the identification of leaner cuts of meat. The program was implemented through grocery stores in two of the towns selected for MHHP intervention. Population based telephone surveys indicated that respondents in the intervention towns were more aware of the lean meats program than those in the comparison communities. Knowledge of lean cuts of meat and low-fat preparation methods also increased as a result of the program. Independently collected sales data from five participating and two control stores provided some indications of a greater interest in lean cuts and 80% lean ground beef as a result of the intervention program. Programs such as this have potential for community-wide nutrition education. PMID- 3339208 TI - Activities of and time spent by the project dietitian in implementing a custom designed decision support system for a computer. AB - Part 1 of this study involved development and implementation of a prototype of Interactive Foodservice Decision Assist Methods (IFDAM) software. A 1-day menu from the Health Center of Methodist Health Services, Inc., which included 161 menu items and 181 ingredients, composed the data base. The prototype was used to test transfer procedures from the mainframe computer at the university to the one at the hospital and to test the program and train users. Three supporting documents were written. The Procedure Manual described methodology for data collection and use of IFDAM at the Health Center. The Data-Entry Manual explained the use of the microcomputer for entering information into IFDAM. The User Manual illustrated the command structure of IFDAM. Part 2 of the study included the addition of data from five cost centers, which were serviced from the central production facility of the Health Center. Six-week-cycle menus and all ingredient files in the foodservice were incorporated into the data base. The data totaled 998 menu items and 660 ingredients. Time spent by the project dietitian on development of data bases and support manuals, completion of data forms, data entry and transfer, conferences, and training totaled 362.10 hours and 898.75 hours in Parts 1 and 2, respectively. The project required 30 months to complete. Problems, classified as equipment, program, or personnel, delayed implementation. PMID- 3339207 TI - A comprehensive nutrition case management system. AB - An innovative, state-of-the-art, comprehensive nutrition assessment and case management system has been developed by nutritionists (R.D.s) and public health nurses with the San Bernardino County Public Health Department in California. The system consists of three major components: flowsheets for the infant, the child, the perinatal client, family planning, and the adolescent/adult/aging client; a manual that defines and describes nutrition assessment guidelines and interventions; and an appendix that includes resource/reference information. Distinct advantages and unique features of this system include the following: (a) decrease in charting time; (b) precise documentation; (c) a workable diagnostic tool for implementing nutrition interventions; (d) a standard for consistent, quality nutrition care; (e) computer adaptability; and (f) easy accessibility for quality assurance audits. PMID- 3339210 TI - Microcomputer programs for diet analysis: a comparative evaluation. PMID- 3339209 TI - Effect of systemized mailings on consumer knowledge of cholesterol modifications. PMID- 3339211 TI - Post-partum breast feeding support: impact on duration. PMID- 3339212 TI - Health claims on food labels: an American Dietetic Association perspective (ADA timely statement). PMID- 3339213 TI - Late onset schizophrenia-like illness. AB - A chart review of 658 psychiatric inpatients aged 65 years or older with a clinical diagnosis of schizophrenia revealed 32 patients (4.8%) with onset of symptoms after aged 45 who met DSM-III criteria for schizophrenia (except age of onset). Clinical course and response to treatment revealed only 25% to follow an unequivocally schizophrenic pattern. Almost 20% demonstrated substantial affective symptomatology, whereas 15.6% had a brief psychotic episode with full remission, and 40.6% showed signs of organic deterioration. These results suggest that diverse underlying pathologic processes may present initially as late onset schizophreniform illness. The presence of depressive symptoms and assaultive behavior on admission predicted good treatment response while sensory deficits and development of signs of organicity were associated with poor treatment response. PMID- 3339214 TI - Longitudinal study of death and institutionalization in patients with primary degenerative dementia. AB - We studied the outcome of 101 patients with primary degenerative dementia. The patients were outpatients at the time of the initial evaluation, and all had family caregivers. There were substantial differences in mortality and institutionalization between the mild and advanced patients, as defined by scores on mental status examination. Similar differences in those two outcomes were also evident when the patients were stratified by scores on activities of daily living and disruptive behavior assessments. Thus, certain patient characteristics may be of value in predicting risk for institutionalization and death. PMID- 3339215 TI - Assessing health differences in an elderly population: a five-year follow-up. AB - A sample of several hundred elderly residents of Alameda County was recontacted after 5 years to determine the effects over time of different social support and demographic variables on health status. The follow-up investigation demonstrated a strong relationship between respondents' social support resources in 1980 and their subsequent self-rated health. Indeed, social contacts in 1980, together with age and financial need, enabled us to correctly "predict" respondents' subsequent health status in close to two-thirds of the cases. As anticipated, however, the variable most strongly associated with self-rated health in the earlier cross-sectional study--illness of a mate during the preceding 6 months- disappeared as a predictor variable in the longitudinal study. This finding is in keeping with the literature on bereavement and other stressful life events which demonstrates that the health impact of such stressors is in most cases time limited. The study findings support earlier research demonstrating the important role of social support for health maintenance and disease prevention in the elderly. They further underscore the need for intervention strategies designed to strengthen the network resources of those elders at high risk for social isolation. PMID- 3339216 TI - Hospital versus random digit dialing controls in the elderly. Observations from two case-control studies. AB - Finding an optimal source of controls is a major consideration in the design of case-control studies. While hospital patients can provide a relatively economical and convenient source of controls, hospital controls may have diseases independently associated with the exposures being studied. Results of a recent case-control study of multiple myeloma suggest that the problems of using hospital controls may be exacerbated in studies of diseases affecting the elderly, especially when considering risk factors which might be associated with chronic diseases. Apparently, the authors have encountered a modern analog of "Berkson's bias" in which cancer cases are referred to a tertiary care center for a single disease. On the other hand, noncancer patients who might serve as controls tend to be referred selectively if they have multiple diseases. This article reports some of the difficulties encountered in a case-control study whose mean case age was 63.4 years and suggests that community controls selected by random digit dialing may be preferable to hospital controls for hypothesis generating case-control studies of diseases in the elderly. PMID- 3339218 TI - Adult hypophosphatasia in a geriatric patient. PMID- 3339217 TI - Effects of physical exercise for elderly patients with physical impairments. AB - Exercise is known to preserve many physiological responses in the healthy elderly, yet those with physical impairments are often discouraged from exercising. The authors studied the effects of a closely supervised exercise program designed specifically for elders with health problems and functional limitations. Tests, selected for their relevance to clinical patient management, included the Self Evaluation of Life Function questionnaire, treadmill performance, and tests of autonomic nervous system and neuromotor functions. Ambulatory volunteers, aged 64 to 83 years, with noncardiac health problems, were randomly assigned to a control group (CG; n = 17) or a 16-week exercise group (EG; 3 hr/wk, n = 18). Nine of the control and 13 of the exercise subjects completed the study. All EG dropouts were due to illness. EG attendance averaged 87%, and subjects trained at a heart rate (HR) of 103 +/- 5 beats/min (SD) (98% of prescription HR). Though EG test responses showed a tendency to improve, none reached statistical significance. This result was affected by the small number completing the study and the variability inherent in such a sample. Though these impaired elderly subjects enthusiastically and safely participated with high attendance and at an exercise intensity adequate to expect benefit, measurable training effects were not demonstrated. PMID- 3339219 TI - AIDS as a cause of dementia in the elderly. AB - It has been recognized that AIDS can present initially as dementia without other neurological or clinical manifestations. In addition, HIV-contaminated blood transfusions in the elderly seem to be underreported. Because of these findings, dementia in the elderly may be misdiagnosed as Alzheimer's disease or other causes of senile dementia. This paper reports on one patient who presented with a diagnosis of Alzheimer's disease and was later found to have AIDS. PMID- 3339221 TI - Reducing the hospitalization of nursing home residents. PMID- 3339220 TI - The ethics committee in the nursing home. Results of a national survey. AB - As the complexity, prevalence and visibility of ethical dilemmas in medical care of the elderly have grown, hospitals and nursing homes have attempted to develop mechanisms for responding to these difficult ethical issues. While it is known that many hospitals rely on education and advice provided by an ethics committee, little data exist on the responses of nursing homes, despite the unique nature of ethical issues in a long-term care setting. The present paper reports findings from a national survey of administrators of 4504 nursing homes in which mechanisms for handling ethical dimensions in patient care were investigated. Results from 29% of respondents reveal that few nursing homes have established ethics committees (2% of the sample) and that committee formation appears positively associated with facility size and religious affiliation. Committees that have been formed engage in policy review (81%), advisory case review (67%) and education (45%). Few committees include patients or their representatives as members, and few have the authority to make binding decisions (26%). While the most effective response to ethical issues in medical decision-making is being debated, standing committees provide one means to contribute to the quality of decision-making by patients, their family members and their physicians. However, broader inclusion of patient perspectives and education of members regarding ethical analysis are necessary precursors to effective functioning of ethics committees in long-term care. PMID- 3339222 TI - Effects of wasting malnutrition in male and female elderly. PMID- 3339223 TI - Age at onset in Alzheimer's disease. PMID- 3339224 TI - Livedo reticularis and sudden death. PMID- 3339226 TI - Health and function in the old and very old. AB - This report advocates conceptual separation and parallel assessment of medically diagnosed health conditions and functional disability in clinical and epidemiological studies of the aged. Data from a study of urban elderly are presented to demonstrate how this can be done and to reexamine the meaning of self-reported illness and disability. One hundred thirteen subjects 74 to 95 years old, recruited from a longitudinal study of a representative sample of the elderly population of Cleveland, Ohio, participated in structured interviews and epidemiologically based medical examinations, conducted by a physician-nurse team at the place of residence. The presence or absence of 11 common chronic conditions was determined according to preestablished criteria, by self-report and, separately, by medical diagnostic evaluation. Functional disability was estimated by self-report and by physician-nurse assessment, using established measures of mobility and activities of daily living. Results indicate that interview self-report can provide useful estimates of the prevalence of medical conditions and functional disabilities in elderly populations, although self report alone is not a sufficiently sensitive measure to be used for case-finding or diagnosis. When functional disabilities are matched against the specific medical conditions that cause them and disease-specific mortality is also taken into account, a three-dimensional classification results that has implications for future clinical and survey work with the elderly. PMID- 3339225 TI - Direct assessment of activities of daily living in Alzheimer's disease. A controlled study. AB - The relationship between severity of dementia and performance in four experimental tasks was studied in nine patients with Alzheimer's disease and nine age-matched controls. The experimental tasks were developed in order to establish a direct measure of functional performance in common activities of daily living. In the Alzheimer's patients, significant but moderate positive associations were found between the Clinical Dementia Rating Scale (CDR), a comprehensive rating tool designed specifically for Alzheimer's disease, and performance on the experimental tasks. A significant correlation was also found between the results of the Short Portable Mental Status Questionnaire (SPMSQ), a less specific dementia assessment instrument, and the CDR but not between the SPMSQ and the performance measure. When compared to nine normal subjects matched for gender, age, and education, the cognitively impaired subjects required more assistance and time (P less than .01) in completing the tasks. The findings support the conclusion that severity of dementia and performance on activities of daily living tasks are related but distinct concepts and should be measured separately. PMID- 3339227 TI - Quantifying the ease or difficulty older persons experience in opening medication containers. AB - To compare the difficulty experienced by older persons in using various medication containers, 50 noninstitutionalized women and men over 60 years of age were timed while opening 15 containers. Pill and liquid medication bottles with and without child-resistant closure mechanisms were tested. In addition, other types of medication packaging were evaluated, such as nitroglycerin patches. All subjects could open each of the non-child-resistant containers, though none of the child-resistant containers could be opened by all participants. For child resistant containers, dramatic differences were observed in the proportion of subjects who could open the various designs and in the amount of time required. Subjects' comments and observations of subjects' efforts provided possible reasons for some of these differences. The results suggest that when child resistant containers are used, consideration of the type of medication container can significantly reduce inconvenience to older persons. Containers without child resistant mechanisms provide the best option for elderly people when access by small children is not an issue. PMID- 3339228 TI - Immunization of elderly people with high doses of influenza vaccine. AB - Healthy ambulatory elderly were immunized with increasing doses of the 1984-1985 influenza vaccine formulation. Two types of vaccines, split-product vaccine (SPV) and whole virus vaccine (WVV), were used. Three different doses, 0.5 mL (the standard volume, 1X), or 1.0 mL (2X), and 1.5 mL (3X) of each of the two vaccines were compared. The size of each of the six groups was between 23 and 26 subjects. The mean ages in each of the groups ranged from 71 to 74 years. No difference in local or systemic reaction was noted among the six groups. A dose-response effect was observed for the SPV recipients to the influenza A/Chile/83 (H1N1) strain. The geometric mean hemagglutination inhibition (HI)titer (GMT) was 1:76 after the 3X dose vs 1:38 after the 1X dose (P less than 0.025). To the influenza A/Philippines/82 (H3N2) strain the GMT was 1:70 after the 3X dose vs 1:43 after the 1X dose. A similar trend was noted for the influenza B/USSR/83 strain. A (HI) titer of greater than or equal to 1:40 for all the strains was seen in greater than 70% of the split product vaccine recipients only after the 3X dose. For the WVV recipients, increasing doses did not result in increasing GMT for any of the three vaccine strains. In addition, HI titers greater than or equal to 1:40 were not uniformly seen in greater than 70% of the vaccine recipients at any of the three whole virus vaccine doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339229 TI - Risk factors for dehydration among elderly nursing home residents. AB - Dehydration is the most common fluid and electrolyte disorder among the elderly, yet risk factors are not known. This study identifies risk factors for dehydration in acutely ill nursing home residents. All 339 elderly resident of two nursing homes who developed an acute illness requiring hospitalization during 1984 were included in the study. The 173 patients having a serum Na less than 150 mg/dL and blood urea nitrogen to creatinine ratio (BUN:Cre) less than 20 were designated controls; 91 patients having a serum Na greater than 150 mg/dL or a serum BUN:Cre greater than 25 were designated cases. Odds ratios (OR) and confidence intervals were calculated for age, sex, chronic conditions, acute illnesses, medications, functional status measures, and season. Acutely ill dehydrated patients were female (OR, 3.3); over 85 years old (OR, 2.2); had more than four chronic conditions (OR, 4.0); took more than four medications (OR, 2.8); and were bedridden (OR, 2.9). Among the most severely dehydrated (serum Na greater than 150 mg/dL and BUN:Cre greater than 25), the odds ratios for the above factors were strengthened and other factors, such as inability to feed oneself and type of acute diagnosis, emerged as risk factors. Among the variables unrelated to functional status, laxatives (OR, 3.2) and chronic infections (OR, 1.8) were risk factors. We conclude that a group at high risk for dehydration can be defined and that they are better characterized by the number of chronic diseases and debilitated functional status than by acute disease processes. PMID- 3339230 TI - Are Alzheimer patients healthier? AB - At an active outpatient geriatric program the gerontological team observed that Alzheimer patients appear to have fewer physical ailments than other elderly patients. To test this hypothesis, we reviewed a sample of 348 clinic patients. One hundred forty-three had a normal mental status; 75 had Alzheimer's disease as defined by DSM-III criteria; 139 had an abnormal mental status attributed to other etiologies. The number of diagnoses was compiled in each of the three groups. The average number of diagnoses in the nondemented group was 5.0 in males, 5.4 in females. In the non-Alzheimer abnormal mental status group, the average number was 5.5 in males, 4.6 in females. In contrast, the number of diagnoses in the Alzheimer group was 2.9 in males and 2.8 in females (P less than 0.0001). Cardiovascular diseases, hypertension, and cerebrovascular accidents were less frequent in the Alzheimer population. This study suggests that Alzheimer patients are physically healthier than non-Alzheimer elderly patients. PMID- 3339231 TI - Treatment of the elderly brain-injured patient. Experience in a traumatic brain injury unit. AB - Recovery from traumatic brain injury in the elderly is a subject rarely discussed in the medical literature, and existing data is conflicting. The Traumatic Brain Injury Unit at Gaylord Hospital routinely admits patients over 50 years of age for rehabilitation after significant closed head injury. Of the 26 elderly head injured patients reviewed over a four-year period for this study, 85% eventually returned to a home setting, with more than half independent in activities of daily living. Based on this encouraging data, it is suggested that the older head injured patient can recover from severe closed head injury. PMID- 3339232 TI - Use of the Cornell scale in nondemented patients. AB - The Cornell scale is a 19-item clinician-administered scale of depression that uses information from interviews with both patients and their caregivers. The Cornell scale has been validated in demented patients. In this study, the Cornell scale was psychometically tested in nondemented geriatric subjects by administering it to 15 depressed patients, 15 patients with other psychiatric diagnoses, and 15 normal control subjects. The Cornell scale had high interrater reliability (Cohen's kappa = 0.74), internal consistency (Kuder-Richardson's coefficient = 0.98), and sensitivity, and correlated significantly (Spearman's r = 0.81) with Research Diagnostic Criteria psychiatric diagnoses associated with various intensity of depression. To our knowledge, the Cornell scale is the only depression-rating instrument that has been validated in both demented and nondemented geriatric subjects. PMID- 3339233 TI - Hyperthyroid chorea in an elderly woman associated with sole elevation of T3. AB - A 72-year-old woman presented with chorea, mild tachycardia, and elevation of T3RIA. T4 was not elevated until the third determination. Chorea resolved with treatment of hyperthyroidism. This case represents the first case of T3 hyperthyroid chorea and the oldest patient with hyperthyroid chorea described in the literature. It demonstrates yet another subtle way in which thyroid disease can present in the elderly. PMID- 3339234 TI - Problems with pill packaging. PMID- 3339235 TI - Relationship of depression to hypothyroidism in geriatric patients. PMID- 3339236 TI - Detrusor-sphincter--"pseudodyssynergia". PMID- 3339237 TI - Tests for differential diagnosis of dementia of the Alzheimer's type. PMID- 3339238 TI - Hyponatremic hypervolemia caused by a drug--drug interaction mistaken for syndrome of inappropriate ADH. PMID- 3339240 TI - Eliminating salary inequities for women and minorities in medical academia. PMID- 3339239 TI - Stress in the role constellation of female resident physicians. PMID- 3339241 TI - Selective production of autoantibodies in graft-vs-host-induced and spontaneous murine lupus. Predominant reactivity with histone regions accessible in chromatin. AB - The injection of (C57BL/6 X DBA/2)F1 mice with parental DBA/2 lymphoid cells leads to a lupus-like disease in which IgG autoantibodies are targeted to certain nuclear and cell surface antigens. To investigate further the extent of antibody diversity in this graft-vs-host (GVH) model, we studied the specificity of antihistone antibodies induced by the GVH reaction. High levels of IgG antibodies to histones H1 and H2B were detected whereas responses to H2A, H3, and H4 were only marginally elevated above pre-GVH levels. Immunoblotting analysis further revealed that the response to H2B was focused on epitopes that most likely reside in the N-terminal region. In contrast, F1 mice immunized with H2B/RNA complexes in adjuvant produced antibodies to the N terminus as well as to other regions of the H2B molecule. Thus, the antihistone response stimulated by the GVH reaction is only a fraction of the potentially activatable B cell repertoire. We also determined whether antibodies that arise spontaneously in genetically predisposed lupus strains were restricted in their histone reactivity. The response to core histones was highly variable among individual animals of the NZB/NZW and MRL lpr/lpr strains despite their inbred nature. However, nearly all mice exhibited a preferential reactivity for epitopes in histone regions that are lost after partial trypsin digestion of chromatin. These data demonstrating autoantibody responses that are limited to particular histone regions support a mechanism by which B cells are selectively activated in murine lupus. The predominant production of antibodies to histone regions that are exposed in nucleosomes raises the possibility that chromatin is an antigenic stimulus for histone specific B cells in this disease. PMID- 3339242 TI - Dietary fish oil modulation of macrophage amyloid P component responses in mice. AB - Arthritis-susceptible B10.RIII mice, maintained on either fish oil (FO) or corn oil (CO) diets (5% by weight), and amyloid-susceptible CBA/J mice fed chow diets were given 20 micrograms purified LPS by i.p. injection. Both strains of mice responded to LPS with a 20- to 30-fold increase in plasma amyloid P component (AP) levels. There were no differences in the response between males and females or between FO and CO treatment groups. The data demonstrated that cultured peritoneal macrophages (M phi) respond to LPS stimulation with increased secretion of AP. In contrast to plasma AP levels, the MO response to LPS stimulation, as measured by production of AP, was influenced by both gender and diet. Although M phi from both male and female mice on the CO diet and male mice on the FO diet responded similarly, those from female mice on the FO diet secreted only 25 to 35% as much AP as did the other three groups. There were no dietary effects on the LPS-induced serum amyloid A protein response nor was there detectable serum amyloid A protein produced by the M phi. These results demonstrate that unstimulated, resident peritoneal M phi secrete AP as a normal constituent and in increasing amounts in response to LPS stimulation. PMID- 3339243 TI - Immunoglobulins and complement in demyelination induced in mice by Theiler's virus. AB - Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) produces chronic demyelination and persistent infection in the central nervous system (CNS) of susceptible SJL mice. This series of experiments examined the contribution of humoral immunity and C to myelin destruction. As in multiple sclerosis, mice persistently infected with TMEV had elevated levels of IgG and oligoclonal bands in the cerebrospinal fluid (CSF). Immunoblot studies revealed that even in animals exhibiting profound demyelination, IgG in the serum and CSF was directed primarily at virus antigen rather than at normal myelin components. Inflammatory cells positive for Ig were distributed mainly around blood vessels, but occasionally they infiltrated the spinal cord parenchyma. Rare examples of myelin sheaths positive for IgG were found by immunoelectron microscopy in spinal cord sections from infected mice; the third component of complement (C3) was commonly found in the walls of CNS blood vessels but not on myelin. Neither serum nor CSF IgG from infected mice bound to myelin sheaths or other CNS components in sections of normal syngeneic spinal cord. There were significantly more demyelinating lesions in infected mice depleted of C components with cobra venom factor. These data do not support a humoral autoimmune basis for the CNS demyelination that occurs in association with persistent TMEV infection. However, the humoral immune response directed at TMEV antigens may either limit virus spread or promote virus persistence. PMID- 3339244 TI - Fura-2 secretion and sequestration in macrophages. A blocker of organic anion transport reveals that these processes occur via a membrane transport system for organic anions. AB - Fura-2, loaded into J774.2 macrophages as the acetoxymethyl ester, is sequestered into intracellular vacuoles within 90 min after the beginning of the loading at 37 degrees C. The dye is also efficiently secreted from the cells. Sequestration and secretion of fura-2 reduce the accuracy of measurements of cytosolic free Ca2+ concentration in this cell line. Fura-2 is also sequestered and secreted by J774.2 when the dye is loaded into the cytoplasm as the pentapotassium salt by reversible permeabilization of the plasma membrane. Regardless of the mechanism by which fura-2 is loaded into the cytoplasm, both sequestration and secretion are prevented by 2.5 mM probenecid, a blocker of organic anion transport. Probenecid has no effect on resting or stimulated cytosolic free Ca2+ levels or on FcR-mediated phagocytosis. These findings suggest that macrophages express a transport mechanism for the anionic form of fura-2. This transport system is responsible for the clearance of fura-2 from the cytoplasm of this cell type. Furthermore we suggest that use of probenecid to block secretion and intracellular sequestration of fura-2 may overcome problems arising in the application of this Ca2+ indicator to macrophages and perhaps to other cell types. PMID- 3339247 TI - Duck lymphocytes. II. Culture conditions for optimum transformation response to phytohaemagglutinin. AB - The lymphocyte transformation (LT) test was performed with duck blood lymphocytes in 96-well microtitre trays against nine concentrations (0.1-100 micrograms/ml) of phytohaemagglutinin (PHA). It was found that incubation at 41.6 degrees C (duck body temperature) gave better results than incubation at 37 degrees C, and that a 6 h pulse with [3H]thymidine gave better results than an 18 h pulse. Cell concentration was very critical: successful duck LT required rather high concentrations of cells (approximately 4 X 10(6)/ml, equivalent to approximately 8 X 10(5)/culture) while lower and higher concentrations gave inferior results. Duck serum supported LT optimally when used at a concentration of 10-15%, but a serum pool from adult (approximately 6-month-old) ducks gave superior results to sera from younger birds. Foetal calf serum supported duck LT strongly when used at 20%, but only poorly at 10%, while chicken serum supported duck LT when used at 5-20%. Ultroser G was an ineffective supplement, and the addition of 5% tryptose phosphate broth to other supplements had variable effects. Using optimum culture conditions, maximum LT responses were obtained after 2-3 days' culture, when it was possible to obtain stimulation indices of 500-5000. The addition of PHA to cultures could be delayed for up to 18 h without affecting LT, but thereafter the cells rapidly lost responsiveness. PMID- 3339245 TI - Nonpurulent response to toxic shock syndrome toxin 1-producing Staphylococcus aureus. Relationship to toxin-stimulated production of tumor necrosis factor. AB - Infection of surgical wounds with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus does not usually elicit a purulent response from the host. Because S. aureus is normally a pyogenic pathogen, this phenomenon suggests that strains of staphylococci that produce the exotoxin are able to inhibit the migration of polymorphonuclear neutrophils (PMN) to sites of infection. We have considered that inhibition of leukocyte migration may be an effect of secreted TSST-1 and have studied direct and indirect effects of the exotoxin on migratory functions of PMN in vitro. Preincubation of PMN with TSST-1 produced no inhibition of random motility or FMLP- or C5a-stimulated chemotaxis under agarose. Supernatant fluids from mononuclear leukocytes incubated with TSST-1, however, were potently inhibitory for both PMN random and chemotactic migratory functions. The inhibitor of migration was identified as TNF based upon neutralization by anti-TNF antiserum and its presence in the culture supernatant fluids assayed in terms of cytotoxicity for murine TNF-sensitive L-929 cell line cells. Preincubation of PMN with recombinant human TNF also inhibited subsequent PMN random and chemotactic migratory functions. We propose that TSST-1 inhibits the mobilization of PMN to sites of infection by stimulation of monocyte/macrophage TNF production and suggest that TNF may also contribute to some other effects of toxic shock syndrome. PMID- 3339246 TI - Measurement of the humoral immune response against Streptococcus pneumoniae type 3 capsular polysaccharide and oligosaccharide containing antigens by ELISA and ELISPOT techniques. AB - A sensitive ELISA has been developed to study immune responses in mice against Streptococcus pneumoniae type 3 capsular polysaccharide (S3PS) and hexasaccharide (HS)-protein conjugates derived therefrom. An advantage of the described system is that the same microtiter plates can be used for both ELISA and ELISPOT tests with a standardized washing procedure and diluent composition. S3PS induced predominantly IgM antibodies and minute amounts of IgG as measured by ELISA in serum. This was accompanied by large numbers (greater than 14000) of IgM spot forming cells in the spleen. A shift towards IgG production was achieved by addition of lipid A. HS-protein conjugates induced predominantly IgG antibodies after booster immunization(s). Furthermore these conjugates induced large numbers (greater than 40000) of IgG spot-forming cells (SFC) in the spleen. ELISA and ELISPOT assays on microtiter plates are both reliable and highly reproducible assays for the evaluation of immune responses to S. pneumoniae antigens. PMID- 3339249 TI - A rapid multicolor Western blot. AB - A multicolor Western blotting technique was developed, by which different kinds or different subtypes of interferon were identified with different colors on a single Western blot. This was achieved by sequentially applying different sets of probing antibodies, enzyme-conjugated developing antibodies and enzyme substrates to detect each of the two or more types of interferon on the Western blot. An improved and much faster method of obtaining the same result by the simultaneous application of more than one kind of probing antibodies, the simultaneous application of a mixture of different enzyme-conjugated developing antibodies followed by successive application of different substrates was also described. In addition, a combination of the sequential and simultaneous techniques was used to produce a triple color Western blot. PMID- 3339248 TI - Preparative techniques influencing sedimentation of erythrocytes through the Hypaque-Ficoll medium used in the one-step technique for separation of human polymorphonuclear leukocytes from whole blood. PMID- 3339251 TI - Two new ELISAs using monoclonal H-Y antibody. AB - Biotin-conjugated monoclonal H-Y antibody was used to detect soluble H-Y antigen, directly, in two novel enzyme-based systems: a sandwich or 'capture' ELISA and an inhibition ELISA. In each case, soluble H-Y was readily detected in samples known to contain the antigen, provided that positive and negative samples were compared on an equivalent protein basis. By adding increasing concentrations of inhibitor (antigen) we define the useful range of the assays to be between 0.6 and 20.0 micrograms of added protein. Both sandwich and inhibition ELISAs gave similar results with antigens tested. The methods can accordingly be applied as direct diagnostics in the study of sex determination and in the assignment of gender. PMID- 3339250 TI - An enzyme-linked direct antiglobulin test for assessing erythrocyte bound immunoglobulins. AB - An enzyme-linked direct antiglobulin test (DAGT) for assessing erythrocyte-bound IgG, IgM and IgA is described. The test is carried out in microtitre plates using heavy chain-specific, alkaline phosphatase-linked, goat anti-human globulin reagents with p-nitrophenyl phosphate as substrate. Results are expressed in optical density (OD) units per 3.6 X 10(7) red cells. The method is reproducible, with coefficients of variation of 0.056, 0.093 and 0.087 for IgG, IgM and IgA respectively. The linear relationship between the amount of red cell-bound antibody and the OD reading for each immunoglobulin class shows that the method is suitable for quantitative studies. Healthy individuals were found to have small amounts of immunoglobulin bound to their red cells with mean values of 0.251, 0.087 and 0.128 OD units per 3.6 X 10(7) red cells for IgG, IgM and IgA respectively; there was no difference between male and female subjects. In the clinical situation, the enzyme-linked DAGT was considered to show significantly increased amounts of cell-bound immunoglobulin when the results were more than three standard deviations above the mean and the quantitative results permitted an accurate assessment of the progress and response to treatment of patients with autoimmune haemolysis. PMID- 3339253 TI - Affinity of anti-peptide antibodies measured by resonance energy transfer. AB - Because of the increasing use of monoclonal anti-peptide antibodies we have undertaken to formulate a general method for the measurement of intrinsic association constants characterizing complex formation between peptide and antibody. The method is based on the phenomenon of resonance energy transfer between tryptophan-excited antibody and an appropriate fluorophor conjugated to the amino terminus of the peptide. The fluorophor we have employed is 8-(2-N succinylaminoethylamino)-1-naphthalene-sulfonic acid with an absorption maximum at 344 nm and an emission maximum at 500 nm. The model peptide used was the sequence corresponding to residues 48-60 of the regulatory subunit of aspartyltranscarbamoylase. Three IgG and two IgM affinity-purified monoclonal anti-peptide antibodies were used in the fluorescence titration experiments. A maximum value of 2.1 X 10(6) M-1 was found for the IgG antibodies and a maximum of 2.7 X 10(4) M-1 for the IgM antibodies. These limited results suggest similar behavior for the anti-peptide B cell response with respect to affinity maturation as observed for other specificities. In particular it is likely that the IgM affinities are restricted to the potential available in the germline repertoire of variable region genes and, therefore, express only germline affinities. PMID- 3339252 TI - A turbidometric assay for measuring proteins in culture media. AB - An immunoturbidometric assay was developed for the measurement of proteins in culture fluids of hepatocytes. The assay is simple to perform and avoids the biohazards associated with radioimmunoassays. The limit of detection of this assay exemplified by hemopexin and transferrin is 5 ng/ml protein. This degree of sensitivity is attained by incorporating into the procedure the addition of polyethylene glycol to enhance formation of primary antigen-antibody complexes and of a second antibody to further increase the immune complex size, which favors the ratio of specific to background light scattering. PMID- 3339254 TI - Sandwich-type ELISA for free and bound secretory component in human biological fluids. AB - Three sandwich-type enzyme-linked immunosorbent assays (ELISA) are described for the measurement of free secretory component (SC) and SC bound to IgA (S-IgA) or IgM (S-IgM). These assays do not require preliminary fractionation of the biological fluids to be tested. The specificity of the assays is achieved with monoclonal antibodies specific for free SC (855 SC) and for SC bound to IgA or IgM (8545 SA). The amount of the three SC molecules in various biological fluids is reported. We demonstrate the presence of low levels of free SC in most of these fluids, including normal serum. Moreover our results suggest that S-IgM in serum may result from a non-covalent association between serum IgM and free SC. PMID- 3339255 TI - The measurement of relative antibody affinity by ELISA using thiocyanate elution. AB - A variation of the standard ELISA assay was used to determine the relative affinities of six murine monoclonal anti-dinitrophenol (DNP) antibodies for DNP bovine serum albumin (DNP-BSA). The procedure involved exposing replicate wells containing antibody bound to antigen to increasing concentrations of the chaotropic thiocyanate ion. Resistance to thiocyanate elution was utilized as a measure of affinity and an index (affinity index) representing a 50% reduction in initial absorbance was used to rank the anti-DNP antibodies in order of increasing affinity. For comparison, the affinity constants of the six monoclonals were determined by equilibrium dialysis with 3H-epsilon-DNP-L-lysine as antigen. A significant correlation (P less than 0.02) was observed between the ranking orders obtained using the two methods, thereby demonstrating the applicability of the elution technique for the measurement of relative antibody affinity. PMID- 3339256 TI - Coating of proteins to polystyrene ELISA plates in the presence of detergents. AB - The influence of several detergents on protein coating of polystyrene plates has been investigated. At concentrations equal to or higher than their respective critical micelle concentration (CMC) all detergents prevent attachment of proteins to polystyrene. However, coating of proteins on polystyrene plates can be achieved in the presence of detergents at concentrations 10-100 times lower than their CMC values. There is a strong correlation between the CMC and the detergent concentration inhibiting protein binding to polystyrene by 50%. The rank correlation coefficient for the binding of thyroid plasma membrane antigens was 0.97 (P less than 0.01). The influence of a detergent on the efficiency of protein coating of plastic surfaces also depends to some extent on protein detergent interactions. Attachment of small hydrophilic proteins such as human IgG is more strongly inhibited by detergents than is the coating of hydrophobic thyroid plasma membrane antigens or thyroglobulin. Some detergents do not interfere with protein attachment to plastics and permit subsequent ELISA assays for hydrophobic, detergent solubilized plasma membrane proteins. PMID- 3339258 TI - Surface-bound immunoglobulin E on antigen-presenting cells in cutaneous tissue of atopic dermatitis. AB - Both type I and type IV hypersensitivity reactions have been implicated in the pathogenesis of atopic dermatitis. Using monoclonal antibodies we have identified IgE on the surface of cutaneous dendritic cells in both lesional and nonlesional skin. Double immunofluorescence labeling demonstrates these cells to be antigen presenting cells. Immunoglobulin E (IgE) was not identified on such cells either in atopic individuals with no history of dermatitis or in patients with a range of other dermatoses. Further studies are consistent with IgE being bound to the cell surface via an Fc-IgE receptor. We conclude that this finding is specific for atopic dermatitis and thus may provide a link between the two types of hypersensitivity reactions frequently observed. PMID- 3339257 TI - The identification of prothymosin alpha-like material in vertebrate lymphoid organs by a radioimmunoassay for the N-terminal decapeptide. AB - A radioimmunoassay (RIA) is described for the detection and quantitation of prothymosin alpha (ProT alpha), and its N-terminal fragments containing as a minimum the first ten amino acid residues. This range of peptides includes thymosins alpha 1 (T alpha 1) and alpha 11 (T alpha 11). Antibodies against T alpha 1 and the tracer T alpha 1(1-10)Tyr11(125I), an analogue of the major epitope, were utilized in this RIA. 50% displacement of the ligand was observed with 1.3 pmol of T alpha 1 and 6.4 pmol of ProT alpha. The partially homologous parathymosin alpha (ParaT alpha) showed less than 2% crossreactivity with ProT A. Sephacryl S-200 gel filtration separation of the peptides of calf thymus, chicken spleen and trout spleen extracts prepared by a method eliminating proteolysis, combined with the above RIA, showed the presence of a major immunoreactive peak. Its elution volume corresponded to that of rat ProT alpha (apparent mol. weight 36,000) for both calf (37,000) and chicken (35,000) tissues. In trout it corresponded to a significantly higher molecular weight (62,000). No detectable levels of shorter fragments, including T alpha 1, were observed in any of the above species. The levels of ProT alpha-like peptides in calf thymus, chicken spleen and trout spleen were found to be 246, 8.6 and 7.7 micrograms respectively, of rat ProT alpha equivalents per gram of fresh tissue. The significance of the presence of ProT alpha-like polypeptides in vertebrate species as distant as fish and mammals, the absence of short T alpha 1-like fragments, and the relative conservation of the N-terminus as suggested by the RIA is discussed. PMID- 3339260 TI - Macroconidial development and germination in Trichophyton mentagrophytes. AB - Trichophyton Mentagrophytes was investigated for macroconidial development with particular emphasis on the conidial ageing by light and scanning electron microscopy. Macroconidial germination was also studied under various conditions. Sabouraud glucose agar supplemented with 3% NaCl was used to enhance production of macroconidia. After a long-term cultivation macroconidial compartments changed to spherical thick-walled structure. Some 12-month-old macroconidia were still capable of germination. A wide range of temperature (15-37 degrees C), and inoculum of less than 1 X 10(5) conidia per ml of rich media were appropriate for macroconidial germination. The germination process of macroconidia was highly tolerant to NaCl. A small fraction of the conidia were able to germinate even in distilled water without activation. Effect of freeze-thaw or ultraviolet irradiation on macroconidial germination was determined. PMID- 3339259 TI - Assignment of three patients with xeroderma pigmentosum to complementation group E and their characteristics. AB - Three cases belonging to xeroderma pigmentosum (XP) complementation group E were analyzed clinically and photobiologically. The three Japanese patients were a 50 yr-old female (XP80TO), a 42-yr-old female (XP81TO), and a 41-yr-old female (XP82TO). They were assigned to complementation group E by the cell hybridization study. All showed lowered minimal erythema doses between those of normal Japanese and XP group A subjects at wavelengths of 280, 290, and 300 nm of monochromatic ultraviolet (UV) light. Patients XP80TO and XP81TO, but not patient XP82TO, showed a delayed peak reaction at 48 h to UV erythema. All fibroblast strains from these patients had a reduced level of 40%-44% unscheduled DNA synthesis (UDS) after irradiation with 10 J/m2 of 254 nm UV. Primary cultured epidermal cells from these patients exhibited a relatively low level of UDS (ie, 38%-51% of normal epidermal cells). All of the group E fibroblast strains were twice as sensitive to 254 nm UV killing [n (extrapolation number) = 1.3-1.8, Do (mean lethal dose) = 2.2-2.8 J/m2)] as normal fibroblasts (n = 1.5, Do = 5.0 J/m2). All of the above group E patients had mild XP symptoms, but not neurological abnormalities, at the fifth decade of age. Patients XP80TO and XP81TO had developed skin malignancies (patients XP80TO developed three basaliomas; patient XP81TO developed two basaliomas) at the ages of 46 and 41 yr, respectively. PMID- 3339261 TI - A first approach to an action spectrum for 8-MOP phototumorigenesis in mice. AB - Groups of hairless albino mice were treated with 8-MOP and exposed to a fixed daily dose of UVR obtained from one of four different emission spectra. Each spectrum was obtained by filtering a xenon arc source with a different WG filter. The resultant spectra showed differences in their proportions of shorter UVA wavelengths. A decreased proportion of the shorter wave bands systematically increased the time to first tumor. These data suggest that the action spectrum for 8-MOP sensitized phototumorigenesis is similar to that of acute 8-MOP action spectra in mammalian skin, which usually show maximal activity in the 320-335 nm region. PMID- 3339262 TI - Detection of immunoglobulin G antibodies in melanoma sera reactive with intracellular proteins. AB - Immunoglobulin G (IgG) antibodies reactive with intracellular components of transformed cells were detected in 26/35 sera from patients with melanoma using immunofluorescence and/or Western blotting. By extracting cellular proteins with either sodium dodecyl sulphate or moderate concentrations of salt (400 mM NaCl), the protein antigens were partially characterized by immunoblotting procedures. Although considerable heterogeneity in the molecular weights of the protein antigens was observed, two common groups were delineated. The anti-Pol antibodies reacted with 30 kd cytoplasmic protein and the anti-Ca antibodies recognized acidic high molecular weight (75-95 kd) proteins. These antigens were detected in all transformed cell lines tested, but were not restricted to them. Anti-Ca and anti-Pol antibodies were not found in sera from patients with other solid tumors or in systemic lupus erythematosus. PMID- 3339263 TI - Electron probe analysis of human skin: determination of the water concentration profile. AB - The water concentration profile across rapidly frozen human epidermis has been measured using electron probe analysis and analytical electron microscopy. Determinations were made within the cytoplasm of individual cells. From the basal layer, the water content remained relatively constant or decreased slightly across the viable tissue and decreased approximately linearly across the stratum corneum. A considerable discontinuity in water content occurred between these two regions over the stratum corneum-stratum granulosum junction and the last granular cell layer. The dominance of the water profile by a discontinuity suggests water loss is governed by a partitioning process, presumably a partitioning into the lipid domain. A water discontinuity offers important functional advantages in the conservation of substances within the body and in protection from intruding molecules. PMID- 3339265 TI - Rapid and sensitive analysis of 8-methoxypsoralen in plasma. AB - A new method has been developed to extract 8-methoxypsoralen (8-MOP) from human plasma and to prepare samples for high performance liquid chromatography (HPLC) analysis. Plasma samples are passed through solid phase extraction cartridges that are essentially HPLC "microcolumns" consisting of a bonded silica sorbent that, after activation, selectively retain 8-MOP and then release it when exposed to an eluting solvent. The 8-MOP collected from the cartridge is analyzed by reversed phase HPLC. With this new technique, the 8-MOP is completely recovered and as little as 10 ng/ml can be detected in a 1-ml plasma sample. The average plasma level in a series of 17 patients who had ingested Oxsoralen (approximately 0.6 mg/kg) was 117 ng/ml (+/- 79). PMID- 3339264 TI - The nonpolar lipids of pig epidermis. AB - Epidermis was removed from several sites on the intact bodies of each of seven pigs and the lipids were extracted and analyzed by thin-layer chromatography. The principal nonpolar components were cholesterol, free fatty acids and cholesteryl esters. Small and variable amounts of paraffin hydrocarbons, triglycerides, and an unidentified lipid were noted. In a series of time-course experiments, epidermal lipids were labeled by intradermal injection of [1-14C] acetate at varying times up to 21 days before removal of the epidermis. The hydrocarbons never acquired radioactivity, while the triglycerides retained label only for about 1 day after injection. Squalene and lanosterol retained considerable radioactivity for up to 12 h after labeling. Radioactivity appeared in free fatty acids and cholesteryl esters 2-3 days after labeling and began to decline after 21 days. Epidermis from uninjected sites did not acquire significant radioactivity. From these results it was concluded that cholesterol, cholesteryl esters and free fatty acids are synthesized locally in the epidermis and remain until lost by desquamation. Triglycerides are also synthesized but do not persist into the stratum corneum, so the small amounts found there may be environmental contaminants. Alkanes are not synthesized, and are most probably derived from petroleum waxes. PMID- 3339266 TI - Relationship between in vitro tumor stem cell assay and in vivo antitumor activity using the P388 leukemia. AB - The relationship between in vitro tumor stem cell sensitivity and in vivo antitumor efficacy using 13 active antineoplastic agents was examined by means of the intraperitoneal P388 mouse leukemia system. The doses, which produced a 50% increase in life span after one, five and nine days of treatment, were all significantly correlated with the in vitro concentration producing a 70% reduction in colony formation during a seven-day continuous drug exposure. The five-day correlation was the best, followed by nine days and one day. Correlations were not improved by corrections for either in vitro drug stability or toxicity (LD50). The highly significant correlations observed in this simple retrospective analysis provide a basis for the development of more sophisticated models for the prediction of in vivo results from in vitro data. PMID- 3339267 TI - Influence of polycations on glomerular immune complex localization. PMID- 3339268 TI - Bacterial clearance in the respiratory tract. PMID- 3339269 TI - Glomerular capillary wall charge and antibody binding in passive Heymann nephritis. AB - The interaction between nephritogenic antibodies and antigens in the glomerular capillary wall is influenced by physicochemical determinants such as the electrical charge. We studied the effect of neutralization of a negative glomerular capillary wall (GCW) charge by polyethyleneimine (PEI) on the binding of anti-renal tubular epithelium (RTE) IgG in passive Heymann nephritis. For these studies, glomerular binding of intravenously administered radiolabeled anti RTE IgG was determined in Wistar rats preinjected 30 minutes earlier with either 0.2 ml 0.05% PEI (molecular weight 40,000 kd) or 0.2 ml saline solution; control rats received 0.025 mg radiolabeled nonimmune rabbit IgG (NRIgG) after PEl or saline solution. Glomerulus-bound antibody was measured in saline solution perfused isolated glomeruli 1 hour after this injection. Intravenously administered radiolabeled anti-RTE IgG binding was found to be significantly increased in rats pretreated with PEI compared with those given saline solution. Intravenously administered radiolabeled NRIgG with or without pretreatment with PEl did not bind to the GCW. Administration of PEl had no effect on blood pressure, glomerular filtration rate, or renal plasma flow during antibody administration, which means that hemodynamic changes could not have been responsible for the observed differences in antibody binding. We conclude that binding of PEI to the GCW enhances fixation of anti-RTE IgG, probably because of neutralization of charged sites of the GCW leading to greater accessibility of intrinsic antigens present in the GCW to anti-RTE antibody. PMID- 3339270 TI - Ascites kinetics in cirrhosis: effects of rapid volume expansion and diuretic administration. AB - I examined whether the rate of ascites formation in cirrhosis is increased by volume expansion and whether this rate is related to the intensity of renal sodium retention, and I examined the mechanisms by which ascites is mobilized during diuresis. The plasma-ascites filtration rate (PFR) of intravenously injected iodine 125-labeled albumin (the rate of ascites formation by the liver) after volume expansion with normal saline solution in seven patients was similar to that observed in 14 patients who had not received infusions (0.010 +/- 0.003 vs. 0.013 +/- 0.006 L/hr/m2) and was unrelated to natriuresis both before and after intravenous administration of 80 mg furosemide the previous day (r = 0.04 and -0.36). Diuresis of seven patients who had not received infusions reduced PFR (from 0.679 +/- 0.267 to 0.411 +/- 0.198 L/day, P less than 0.05) and total ascites formation rate (from 3.029 +/- 1.620 to 1.465 +/- 1.053 L/day, P less than 0.02) but not plasma volume (from 3.464 +/- 0.646 to 3.391 +/- 0.775 L). Increases occurred in ascites albumin concentration (from 7 +/- 4 to 9 +/- 4 gm/L, P less than 0.05) and in the ascites/serum albumin ratio (from 0.26 +/- 0.12 to 0.35 +/- 0.13, P less than 0.05) but not in the serum-ascites albumin gradient (portal pressure). Fractional changes in ascites volume and albumin concentration were unrelated (r = 0.20). The calculated rate of ascites reabsorption decreased in five patients during diuresis, indicating that ascites was mobilized by decreased formation. Ascites reabsorption increased in two patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339271 TI - Effect of indomethacin and of prostaglandins on extrarenal erythropoietin production in rats. AB - Indomethacin elevates the plasma erythropoietin titer of hypoxic anephric rats and probably does so by increasing extrarenal erythropoietin production. Because indomethacin is a potent cyclooxygenase inhibitor, we postulated that it alters extrarenal erythropoietin production via its effects on tissue prostaglandin levels. Studies were, therefore, performed to determine the effects of indomethacin on hepatic prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) titers. Indomethacin significantly decreased the PGF2 alpha level but its effects on the PGE2 level were, in most experiments, insignificant. We next studied the effects of infusing PGF2 alpha and PGE2 on the plasma erythropoietin levels of hypoxic rats. PGF2 alpha significantly reduced the plasma erythropoietin titer of anephric rats and neutralized the effect of indomethacin when both substances were administered. PGE2 infusion, on the other hand, did not significantly affect the plasma erythropoietin level of anephric rats. The data support the conclusion that PGF2 alpha is a potent inhibitor of extrarenal erythropoietin production, and that indomethacin enhances the rate of extrarenal erythropoietin production by reducing the PGF2 alpha titer in the liver. PMID- 3339272 TI - Impairment of renal function by stroma-free hemoglobin in rats. AB - Hemoglobin infused into rats was excreted mainly by the kidneys. The effects of hemoglobin on renal tubular functions were investigated in this study. During intravenous infusion of 6% stroma-free hemoglobin (SFHB) solution, there was a 30% reduction in glomerular filtration rate (GFR). The reduction in GFR was directly related to the urine hemoglobin concentration. The rate of urinary sodium excretion (8.2 mumol/min) was significantly higher than the control rate (2.8 mumol/min), suggesting proximal tubular damage in the presence of intratubular hemoglobin. This was further substantiated by the demonstration of a 10-fold increase in urinary N-acetyl-beta-D-glucosaminidase (NAG) activity during SFHB infusion. In contrast, dextran-hemoglobin (DXHB) infused into rats was not excreted by the kidneys. During the infusion of 6% stroma-free DXHB solution, there was no significant change in the GFR. Urinary sodium excretion was lower than the control value whereas urinary NAG activity was slightly elevated. The observations suggest that the presence of hemoglobin in the renal tubules gives rise to impairment of tissue function and structure. DXHB, on account of its larger molecular size, does not enter into the renal tubules, and therefore does not cause such impairment. PMID- 3339273 TI - Myristyl-gamma-picolinium chloride suppresses cartilage and synovial membrane glycosaminoglycan synthesis. AB - Myristyl-gamma-picolinium chloride (MGP) is a novel constituent of methylprednisolone acetate suspensions used for intra-articular corticosteroid therapy. Hyaluronic acid synthesis in organ cultures of normal canine synovial villi incubated with MGP was reduced in proportion to MGP concentration. Similar dose-dependent inhibition of sodium sulfate S 35-labeled glycosaminoglycan synthesis was observed in organ cultures of canine articular cartilage treated with MGP. In comparison, the intact cartilage of cultured femoral condyles appeared less sensitive to MGP inhibition of glycosaminoglycan synthesis. Cartilage and synovium were examined 4 hours after an intra-articular injection of either MGP or its vehicle into canine stifles. No differences in Na2(35)SO4 glycosaminoglycan synthesis were observed between cartilage organ cultures prepared from the MGP-treated and the contralateral vehicle-treated joints, but in four of the five dogs studied less hyaluronic acid was synthesized (P less than 0.05) by synovial cultures from joints exposed to MGP than by cultures from the contralateral joints. Synovium from the MGP-treated joints remained capable of phagocytosis. These observations indicate that at clinically relevant concentrations MGP can inhibit synovial hyaluronic acid synthesis, but has little metabolic effect on normal articular cartilage. PMID- 3339275 TI - Survival of rabbit platelets labeled with gallium 67. AB - The viability of rabbit platelets labeled with radioactive gallium was determined to analyze the feasibility of using platelets labeled with gallium 68 as an imaging reagent for positron emission tomography. Platelets were labeled with a complex of the longer lived gallium 67 and mercaptopyridine-N-oxide (MPO) or with sodium chromate Cr 51. Their survival after transfusion was measured. Labelling efficiency of 67Ga-MPO was 6.5% to 45.8% (26.8% +/- 2.8%) when platelets were suspended in saline solution, but was much lower (1.6% +/- 0.8%) in plasma. Platelets labeled with either radioisotope in a saline medium survived as well as platelets labeled with 51Cr in plasma. Recovery values 1 hour after transfusion and mean platelet survivals were 68.6% +/- 4.9% and 3.4 +/- 0.2 days for 67Ga in saline solution, 76.5% +/- 6.8% and 3.8 +/- 0.5 days for 51Cr in saline solution, and 73.7% +/- 7.4% and 3.6 +/- 0.5 days for 51Cr in plasma. Labeled platelet concentrates always contained extra radioactivity not firmly bound to viable platelets. A postlabeling wash in saline solution did not reduce this contamination and resulted in reduction of the number of viable platelets. The results showed that rabbit platelets labeled with 67Ga-MPO survived in the circulation as well as those labeled by a standard protocol with sodium chromate Cr 51. PMID- 3339274 TI - Pulmonary hypertension and edema induced by platelet-activating factor in isolated, perfused rat lungs are blocked by BN52021. AB - The experimental intravenous administration of platelet activating factor (PAF) induces pulmonary hypertension and directly or indirectly increases capillary permeability. Selective PAF antagonists BN52021 and L652-731 have been shown to inhibit the action of PAF in vitro and in vivo. Using a unique isolated perfused rat lung model, we measured the effect of these PAF antagonists on PAF-induced pulmonary hypertension and edema. Isolated rat lungs were perfused with Krebs Henseleit solution. The right and left pulmonary arteries were dissected so that they could be perfused selectively, permitting the use of one lung as an internal control for a specific pharmacologic challenge. Exposure of one lung to PAF induced an increase of perfusion pressure and wet/dry lung weight ratio in a dose dependent manner compared with the control lung. The PAF antagonists attenuated the increase in perfusion pressure and wet/dry lung weight caused by PAF (0.75 micrograms) in a dose-dependent manner. In addition, prostaglandin F2 alpha induced an equivalent increase in pulmonary pressure without causing a similar increase in lung edema. PAF-induced pulmonary hypertension and the increase in wet/dry lung weight ratio appear to be PAF receptor-mediated processes, and the use of specific antagonists and this technique may be useful probes to determine the role of PAF in pathophysiologic states. PMID- 3339276 TI - Role of antidiuretic hormone in the attenuated furosemide response observed during indomethacin administration. AB - Recently we demonstrated that increased chloride reabsorption in Henle's loop is a major contributor to the blunted furosemide response observed during prostaglandin synthesis inhibition. Because antidiuretic hormone (ADH) modulates chloride reabsorption in the loop and because prostaglandin synthesis inhibition potentiates ADH-mediated water reabsorption, ADH may be necessary for the attenuated furosemide response observed during prostaglandin synthesis inhibition. If such were the case, then prostaglandin synthesis inhibition should have no effect on furosemide's chloruretic response in the absence of ADH. To test this hypothesis, the effect of indomethacin on furosemide chloruresis was determined in homozygous (ADH-deficient) Brattleboro rats and in homozygous Brattleboro rats receiving ADH (2.4 mU/hr) over a short period of time. Furosemide-induced chloruresis was not different (P was not significant) between indomethacin-treated homozygous Brattleboro rats and homozygous Brattleboro rats receiving the indomethacin vehicle (fractional excretion of chloride: 6.28% +/- 1.08% vs. 6.24% +/- 0.98%). However, in ADH-infused Brattleboro rats, furosemide chloruresis was lower in indomethacin-treated rat groups than in vehicle-treated rat groups (fractional excretion of chloride: 3.09% +/- 0.62% vs. 6.61% +/- 0.88%; P less than 0.02) and lower than in indomethacin-treated ADH-deficient Brattleboro rats as well (P less than 0.05). Mean arterial pressure, inulin clearance, and renal blood flow were not different between any groups. Urinary prostaglandin excretion rates were not different between ADH-deficient Brattleboro rats and ADH-treated Brattleboro rats during furosemide administration and were markedly reduced by indomethacin in both circumstances. Thus, ADH is necessary for the blunted furosemide response observed during prostaglandin synthesis inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339278 TI - Abbreviations in the Journal of Laboratory and Clinical Medicine. PMID- 3339277 TI - Identification of abnormal hemoglobins in cord blood by an immunoblot technique. AB - Variant hemoglobins S, C, and FHull were identified in newborn cord blood hemolysates with an immunoblot procedure. The abnormal hemoglobins were originally detected in cord blood hemolysates by cellulose acetate electrophoresis and presumptively identified according to their mobilities. Hemolysates that contained a hemoglobin variant again underwent electrophoresis and were transferred to nitrocellulose membranes. For identification, the membrane was treated with the appropriate rabbit monospecific antiserum and developed with peroxidase-conjugated anti-rabbit IgG or peroxidase-conjugated protein A. After the addition of substrate, a violet reaction developed at the site of the hemoglobin band, signifying an antigen-antibody reaction or a positive reactivity. The use of monospecific antisera in an immunoblot technique allows for confirmed identification of variant hemoglobins in cord blood samples in as little as 5 hours. In some cases in which the variant is near the limits of detectability by protein staining, the immunoblot allows an unequivocal identification. PMID- 3339279 TI - Early observations on the lupus anticoagulant. PMID- 3339280 TI - The need for policy analysis in evaluating the regular education initiative. PMID- 3339281 TI - Improving services for problem learners: rethinking and restructuring. PMID- 3339282 TI - Questions about the regular education initiative. PMID- 3339283 TI - Implementing the regular education initiative in secondary schools: a different ball game. PMID- 3339284 TI - Inservice programs in learning disabilities. National Joint Committee on Learning Disabilities. September 27, 1981. PMID- 3339285 TI - Essential collaborative consultation competencies for regular and special educators. PMID- 3339286 TI - Arguable assumptions underlying the regular education initiative. PMID- 3339287 TI - Identification of multiple low molecular weight placental prolactin-like proteins produced by rat trophoblast cells. AB - Rat trophoblast tissue was found to synthesize a number of low molecular weight proteins possessing prolactin-like characteristics. There appear to be at least three proteins that cross-react with antisera to pituitary prolactin. Two of the proteins had a molecular weight of 25,000, similar to ovine pituitary prolactin, and isoelectric points of 6.8 and 7.0. The third immunoreactive protein had a lower molecular weight (23,500), similar in size to human placental lactogen, and a slightly more acidic isoelectric point of 6.75. The molecular weight variants cross-reacted with an antipeptide serum that was generated to a synthetic peptide representing amino acids 150 to 164 of rat placental lactogen-2 (PL-2). Based on this analysis, we consider these proteins to be related to PL-2. Analysis of trophoblast proteins by gel-filtration chromatography resulted in the identification of another trophoblast prolactin. This material eluted earlier than PL-2-related proteins on a gel-filtration column, possessed prolactin-like activity (determined by competition with ovine pituitary prolactin for rabbit mammary gland or rat liver prolactin receptors) but showed limited cross reactivity with either the antiserum to pituitary prolactin or the antiserum to the PL-2 peptide. We have thus identified multiple low molecular weight trophoblast prolactins, possessing different biochemical and immunological characteristics. PMID- 3339288 TI - Effect of hypothyroidism on the in-vivo and in-vitro uptake of sugar by rat thymocytes and on the stimulatory response to 3,5,3'-tri-L-iodothyronine. AB - We have previously demonstrated, both in vivo and in vitro, that 3,5,3'-tri-L iodothyronine (T3) increases the uptake of the glucose analogue 2-deoxy-D-glucose (2-DG) in rat thymocytes by acting at the level of the plasma membrane. In the present study, the effect of hypothyroidism on the basal uptake of 2-DG by rat thymocytes and their response to T3 was examined. Rats were rendered hypothyroid by thyroidectomy at 21 days of age, and experiments performed with 31- and 56-day old animals. Uptake of 2-DG by thymocytes from hypothyroid rats, both in vivo and in vitro, was greater in 31-day-old animals and less in 56-day-old animals than that in euthyroid rats. In both age-groups, hypothyroidism increased cellular responsiveness to T3, shifting the dose-response curve to the left. Similar results were obtained in experiments in which animals were rendered hypothyroid by KCIO4. Injection of thyroid hormones into rats treated with KCIO4 reversed the effects of hypothyroidism on uptake of [3H]2-DG by thymocytes and their response to T3. From these observations it was concluded that hypothyroidism produces a time-dependent change in basal sugar uptake by rat thymocytes, and increases cellular responsiveness to the effect of T3 at the level of the plasma membrane. PMID- 3339289 TI - Granulated metrial gland cells in the non-traumatized regions of the uterus of ovariectomized mice with deciduomata maintained on progesterone. AB - A study has been made of granulated metrial gland (GMG) cells in the non traumatized regions of the uterus of ovariectomized mice maintained on progesterone and with deciduomata in part of one uterine horn. GMG cells were found in the non-traumatized region of the uterine horns with deciduomata for at least 8 days after induction of the decidual reaction. GMG cells were not found in the contralateral horns without deciduomata. Activation of endometrial stromal cells is characterized by a high mitotic index and, in mice given colchicine, numerous stromal cells were arrested in metaphase in the non-traumatized region of the uterine horns with deciduomata for at least 3 days after induction of the deciduomata. In uterine horns without deciduomata, stromal metaphases were few in number over the same period. A correlation was therefore found between the presence of GMG cells and large numbers of stromal cells in mitosis. There was also a correlation between the absence of GMG cells and small numbers of stromal cells in mitosis. These results are compatible with the hypothesis that the differentiation and maintenance of GMG cells are under the control of endometrial stromal cells. PMID- 3339290 TI - Peripheral progesterone concentrations in the luteal-phase ewe: effects of a beta adrenergic receptor antagonist and two beta 2-adrenergic agonists. AB - Peripheral blood samples were collected at 10-min intervals from three conscious sheep in which ovulation had been induced 6-10 days previously using exogenous hormones. Saline was infused into a jugular vein for about 1 h, followed by the experimental drug for 1-2 h and followed by saline again for a further 2 h. The experiments were repeated following induced luteolysis and ovulation. The infusion of a beta-adrenergic antagonist (propranolol) into three conscious luteal-phase ewes decreased (P less than 0.05) the peripheral progesterone concentration in each animal. Infusions of beta 2-adrenergic agonists (ritodrine and salbutamol) increased (P less than 0.05) the progesterone concentration in four out of eight experiments. The beta-adrenergic antagonist decreased the heart rate and the beta 2-adrenergic agonist increased it; the arterial blood pressure and respiratory rate were unaffected. The decrease in the progesterone concentration in response to the beta-adrenergic antagonist suggests that the normal ovarian secretion of progesterone is partly the result of sympathetic stimulation, and that the sympathetic innervation of the ovary may have a physiological role in modulating progesterone secretion. PMID- 3339291 TI - Effects of transplantation on mouse adrenal chromaffin cells. AB - The effects of long-term transplantation on the ultrastructure of adrenaline- and noradrenaline-storing cells from the adrenal medulla were determined using morphometric methods. Mouse adrenal medulla were freed from the adrenal cortex and grafted into the occipital cortex of the brain. Two types of chromaffin cells were identified by electron microscopy in grafts fixed with glutaraldehyde and osmium tetroxide. Noradrenaline-type cells were predominant and formed 70-80% of the surviving population of grafted chromaffin cells. A minority of the chromaffin cells contained medium-sized granules (140-210 nm in diameter) (medium granule cell; MGC) with finely granular moderately electron dense cores. Morphometric analysis of noradrenaline phenotype cells and MGC cells in transplants showed no significant differences compared with the noradrenaline storing cells of normal adrenal glands. In contrast, noradrenaline-type cells and MGC cells in the grafts had areas of secretory vesicles which were significantly (P less than 0.01) larger and areas of rough endoplasmic reticulum which were significantly (P less than 0.01) smaller than those of the adrenaline-storing cells of normal adrenal glands. It was concluded that long-term transplantation caused no degenerative changes in the ultrastructure of mouse adrenal chromaffin cells. PMID- 3339292 TI - Molecular forms of growth hormone in the chicken pituitary gland. AB - Different forms of GH present in freshly prepared homogenates of chicken pituitary were analysed by high-performance gel permeation chromatography and by immunoblotting following sodium dodecylsulphate polyacrylamide gel electrophoresis, nondenaturing polyacrylamide gel electrophoresis and isoelectric focussing. Chicken GH was found to occur mainly in a monomeric form with a relative molecular mass of 23,500 together with small amounts of interchain disulphide-linked oligomers. No evidence was obtained for proteolytically modified forms of GH nor for a form analogous to the 20K variant of human GH. Isoelectric focussing resolved ten distinct charge variants of chicken GH with isoelectric points between 8.45 and 6.0. The predominant charge variant (pI = 7.85) was present in pituitaries of birds of both sexes at all ages examined (3 114 days) whereas the more acidic forms were not apparent until after day 13. These findings indicate that the chicken pituitary contains different forms of GH, some of which may be developmentally regulated. PMID- 3339293 TI - Opioidergic modulation of the oestradiol-induced LH surge in the rat: roles of ovarian steroids. AB - Sex steroids convey information on the status of the reproductive system, which the brain is able to integrate to promote ovulation, in the form of the LH surge. The present studies examined the influence of alterations in central opioidergic tone to initiate the LH surge, and the roles of oestradiol and progesterone to effect changes in opioidergic tone, by antagonizing this activity using either naloxone or nalmefene (N-cyclopropylmethyl-6-desoxy-6-methylene-noroxy-morphone), a long-acting mu- and kappa-opiate antagonist. The timing and amplitude of the LH surge was examined in (1) cyclic rats in pro-oestrus and (2) ovariectomized rats with varying doses of oestradiol supplementation. Plasma was obtained hourly through an indwelling intra-atrial catheter between 13.00 and 19.00 h, and later assayed for LH and oestradiol concentrations by radioimmunoassay. Rats treated with either nalmefene or progesterone on pro-oestrus demonstrated similar advances in the time of initiation of the LH surge by 1-2 h compared with control rats. The effects of nalmefene and progesterone were evident within 2 and 3-5 h of their administration respectively. Conversely, rats treated with progesterone on dioestrus demonstrated low pro-oestrous oestradiol levels and abolition of the pro-oestrous LH surge, but continuous naloxone infusion restored the pro-oestrous LH surge, with raised oestradiol concentrations. In ovariectomized rats without oestradiol supplentation, nalmefene alone was able to increase basal LH levels, but unable to facilitate a spontaneous rise in LH amplitude indicative of an LH surge. Supplementation with low doses of oestradiol was itself ineffective in facilitating a spontaneous rise in LH concentration, but nalmefene co administration significantly potentiated the ability of low doses of oestradiol to induce augmented LH secretion, in addition to advancing the timing of the spontaneous LH rise. Similarly, progesterone co-administration to ovariectomized, oestradiol-primed rats significantly advanced and augmented LH hypersecretion. The results of these experiments are consistent with the concept that central opioidergic systems normally restrain the initiation of the LH surge, and that blocking opiate receptors removes this inhibition. They advance the hypothesis that oestradiol, the essential signal for LH surge induction, has, as one consequence of its action, the time-specific inhibition of hypothalamic opiodergic tone in the afternoon, which would otherwise restrain the LH surge generating mechanism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3339296 TI - Topical therapy for superficial wounds. PMID- 3339295 TI - Androgen metabolism and regulation of rat ventral prostate growth and acid phosphatase during sexual maturation. AB - Androgen metabolism and the regulation of rat ventral prostate cell proliferation and secretory function were examined during sexual maturation. Changes in acid phosphatase (AP) characteristics were measured as a marker of androgen-dependent prostatic secretory function. In immature (21-day-old) rats, total AP activity per cell was low (14.2 +/- 1.3 mol p-nitrophenol phosphate hydrolysed/h per mg DNA); it increased threefold as the weight, protein and DNA contents of the prostate increased to adult (65-day) levels. This corresponded with significant (P less than 0.001) increases in the staining intensities of three of the four bands of secretory AP on isoelectric focusing gels. The extent of inhibition of AP by tartrate decreased at the same time. Secretory AP is known to be relatively tartrate-resistant. The changes in AP activity occurred after prostatic 5 alpha dihydrotestosterone (5 alpha-DHT) levels increased from 4.6 +/- 0.7 pmol/mg DNA (21 days) to reach a peak of 17.6 +/- 2.3 pmol/mg DNA at 58 days. Prostatic 5 alpha-DHT concentrations were always higher than testosterone levels. Prostatic 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-Adiol) levels were lower than 5 alpha-DHT levels except on day 58 when levels peaked dramatically at 26.2 +/- 5.5 pmol/mg DNA. Changes in prostatic 5 alpha-DHT and 3 alpha-Adiol levels corresponded with changes in 5 alpha-reductase and 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) activities. The oxidative reaction of 3 alpha-HSOR was approximately fourfold higher than the reductive reaction, indicating a preference for the formation of 5 alpha-DHT. The plasma levels of testosterone, 5 alpha-DHT and 3 alpha-Adiol cannot account for their respective prostatic levels, indicating the importance of the steroid-metabolizing enzymes in regulating intracellular androgen levels. Changes in the AP characteristics could be correlated with the androgen status of the prostate. PMID- 3339294 TI - Metabolic actions of cortisol in a macropodid marsupial Thylogale billardierii. AB - In undisturbed pademelon wallabies (Thylogale billardierii) with indwelling jugular venous catheters, an increase in the plasma cortisol concentration from 0.25 +/- 0.05 to 1.35 +/- 0.15 (S.E.M.) mumol/l in 2 h, during i.v. infusion of cortisol at 1.0 mg/kg per h, caused no significant change in the plasma glucose concentration from the control value of 4.26 +/- 0.25 mmol/l. The rates of appearance (Ra) and metabolic clearance (MCR) of glucose, measured by steady state isotope dilution, also did not change significantly from the control values of 14.9 +/- 0.7 mumol/kg per min and 3.52 +/- 0.19 ml/kg per min respectively. Twice-daily i.m. injections of 7 mg cortisol/kg for 7 days caused increases in plasma concentrations of cortisol, from 0.26 +/- 0.02 to 0.66 +/- 0.04 mumol/l on day 7, and glucose, from 5.1 +/- 0.1 to 7.2 +/- 0.6 mmol/l by day 5. The concentration of glycogen in the liver of wallabies fasted for 24 h increased from the control level of 1.17 +/- 0.56 to 5.92 +/- 1.14 g/100 g on day 7 (P less than 0.01), but mean glucose Ra and MCR did not change significantly. Plasma concentrations of alpha-amino nitrogen rose from 2.73 +/- 0.13 to 3.22 +/- 0.12 mmol/l on day 1 and remained at this level. Plasma concentrations of urea rose from 8.59 +/- 0.62 to 9.70 +/- 0.32 mmol/l on day 1, but then declined below the control level. Food intake and urinary excretion of nitrogen did not change in undisturbed animals. However, fasting followed by liver biopsy was accompanied by urinary excretion of nitrogen in excess of food intake, persisting until day 2 of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339297 TI - Endocarditis and mitral valve prolapse. PMID- 3339298 TI - Freon 12 and verruca lesions. PMID- 3339299 TI - Health care decisions for an incompetent patient. PMID- 3339301 TI - Panic disorder: the importance of phenomenology. PMID- 3339300 TI - Health care in Nicaragua. PMID- 3339302 TI - A one-year follow-up of fatigued patients. AB - To better understand the complaint "fatigue" and the characteristic features of patients who present with this problem, a one-year follow-up study was performed in a county health center. One hundred-fifteen fatigued adults were identified using scores on the Rand Index of Vitality (RIV). One hundred thirty-nine patients of similar age, sex, and socioeconomic status were identified as nonfatigued. One year later, these patients were followed up with a chart review, reassessment of fatigue (by RIV score), and a telephone interview. Seventy-three (64 percent) fatigued and 72 (53 percent) nonfatigued patients provided this information. On the RIV, 31 patients moved from the fatigued group to nonfatigued, and 15 nonfatigued patients' scores changed to the fatigued category. Patients categorized as fatigued in 1984 (by RIV score) returned for office visits more often (mean of 3.85 vs 2.51, P less than .05), and developed significantly more new diagnoses (2.75 vs 1.68, P less than .05) over the follow up year, compared with those not fatigued. Fatigued patients also had a greater proportion of diagnoses containing a psychologic component than nonfatigued patients. Persistence of fatigue over the year was significantly associated with race and education (nonwhites and those completing high school remaining fatigued). No significant association between marital status, age, sex, employment status, and either the resolution or development of fatigue over the year was found. PMID- 3339303 TI - Postdate pregnancy in a network of community hospitals: management and outcome. AB - The outcome of 116 postdate pregnancies managed by 14 family physicians in small community hospitals is compared with the outcome of term gestations in the same setting. The postdate pregnancies in this relatively unselected population showed an increase in incidence of macrosomia and fetal heart rate abnormalities similar to those reported from referral centers. The increases in incidence of meconium staining and low Apgar scores reported previously were not found. The postdate patients had more frequent induction, augmentation, and amniotomy, as well as a significant increase in primary cesarean section, decreased use of epidural anesthesia, and fewer assisted deliveries. These data suggest that the community physicians were attaining a favorable outcome in the postdate pregnancy by an active approach to induction and management of labor combined with abdominal delivery of the macrosomic infant showing evidence of fetal distress. PMID- 3339304 TI - Microbiology of adult cellulitis. AB - Needle aspiration of cellulitis sites is commonly advocated to assist in the identification of causative organisms. Twenty-five nondiabetic, adult patients with a clinical diagnosis of cellulitis had site aspirations and blood cultures obtained before antibiotic therapy was initiated. Site cultures were positive in 6 of 25 patients. Blood cultures were positive in 4 of 25 patients. All organisms except one (Enterobacter agglomerans) were staphylococci or streptococci. The gram-negative bacilli were not believed to be a pathogen based on the patient's prompt response to nafcillin. In adult patients who do not have complications, the use of needle aspiration was not supported. Empiric treatment of cellulitis aimed at gram-positive cocci appears to be sufficient. PMID- 3339306 TI - Physician knowledge and attitudes about health insurance after the introduction of capitated health care plans. AB - A two-part closed-end survey similar to a survey done in 1980 was given to 25 family physicians at an academic family medical center to assess physician knowledge about five insurance programs covering most of the patients seeking care in the center, and to assess physician attitudes about the capitated insurance plan with which the clinic was affiliated. Results did not differ significantly from those obtained in a similar survey four years earlier at the same center. Physicians correctly identified benefits offered by insurance programs only about one half of the time and many did not ascertain patient insurance coverage at all. Physicians considered the most important advantages of capitated health care to be the patient protection from fees for services obtained, the coverage for health care maintenance, and the potential for controlling health care costs. Physician-perceived disadvantages included difficulties controlling costs generated by other specialists, dealing with after the-fact authorization requests, controlling access to services, and obtaining information about costs within the capitated system. PMID- 3339307 TI - The development of clinical independence: resident-attending physician interactions in an ambulatory setting. AB - Interactional analysis data from 949 resident-attending physician interactions about the care of 2,975 ambulatory patients were analyzed to test the hypothesis that consultation rates and behaviors would demonstrate a progressive increase in clinical independence and assertiveness. Consultation rates for first-, second-, and third-year residents were 48, 28, and 26 percent, respectively. The mean durations of consultations were 7.7, 6.9, and 6.1 minutes, respectively. Attending physicians visited 20, 12, and 13 percent of the patients of first year, second-year, and third-year residents. The more senior residents displayed fewer of most types of interactional behaviors, suggesting a more focused discussion. Senior residents showed a progressive increase in initiating interactions of all types, demonstrating a kind of clinical independence and educational assertiveness that progressed through three years. There is a growing consensus that teaching in ambulatory medical practices will become widespread, but little information directs educational efforts in these settings. The findings suggest that clinical independence in the ambulatory setting is progressive and that measurements of consultation rates and behaviors expand knowledge about education in ambulatory care. PMID- 3339305 TI - The sequence of panic symptoms. AB - Although much research has focused on the pathophysiology of panic attacks, little work has been done to describe the phenomenon itself. Twenty-one patients with panic attacks were asked to sequence the panic-related symptoms during an attack in an attempt to clarify the phenomenon. Overall, panic symptoms could be grouped into three categories: early symptoms--consisting of dyspnea, palpitations, chest discomfort, and hot flashes; intermediate symptoms--including shaking, choking, feelings of unreality, sweats, faintness, and dizziness; late symptoms-consisting of fear and paresthesias. Based on symptom clustering and temporal relationships, this study describes the panic phenomenon. PMID- 3339309 TI - Patient-to-physician communication on medication use. PMID- 3339308 TI - Splenic artery aneurysm rupture: an uncommon obstetrical catastrophy. PMID- 3339310 TI - Clinic visits following patient newsletter discussing cardiovascular risks. PMID- 3339311 TI - Impact of an HMO on a university-based family practice program. AB - The impact over a 12-month period of a major increase in enrollment of prepaid insurance patients on the clinical, administrative, and educational activities of a university-based family practice residency program is described. Patient services increased by 40 percent, placing a heavy clinical load on faculty and third-year residents. There were significant increases in referral to psychology, psychotherapy, ophthalmology, and otolaryngology specialists. The high demand for services caused logistical difficulties for office and nursing staff. Adaptation to these changes and cost-containment efforts were hampered by institutional relationships. Strategies to manage the impact included hiring additional staff and part-time clinicians, introducing quality assurance and internal control procedures, and repeated orientation to the prepaid plan. Overall, the impact of the plan was of educational value to both residents and faculty. PMID- 3339312 TI - Family medicine in Costa Rica: the beginning. PMID- 3339313 TI - The future of obstetrics in family practice: time for a new direction. PMID- 3339315 TI - Doctor, sign in please. PMID- 3339316 TI - On-site radiology facility. PMID- 3339314 TI - Screening for alcoholism. PMID- 3339317 TI - Mastitis in lactating women. PMID- 3339318 TI - Effectiveness of individualized long-term therapy with niacin and probucol in reduction of serum cholesterol. AB - A retrospective analysis was made of the results of the individualized office management of hypercholesterolemia in 37 patients (25 male, 12 female) with severe atherosclerosis (n = 35) or a predisposition to it (n = 2). The effects of diet instruction, diet and a niacin supplement, and diet plus the niacin supplement and probucol were assessed. Diet alone (n = 37) was prescribed for an average of 4.8 years; diet plus niacin (n = 37) for an average of 2.0 years; and diet plus niacin and probucol (n = 19) for an average of 2.9 years. Each patient served as his or her own control. The maximum serum cholesterol at the beginning of the diet period was 8.69 +/- 2.15 mmol/L (336 +/- 83 mg/dL) (mean plus or minus standard deviation; n = 37). The goal cholesterol was less than 5.20 mmol/L (200 mg/dL). On diet alone the cholesterol level fell to 7.21 +/- 1.27 mmol/L (279 +/- 49 mg/dL) (P less than .001); and goal cholesterol was reached by 12 of 37 patients (32.4 percent), but was maintained in none. On adding niacin, the mean cholesterol fell to 6.21 +/- 1.16 mmol/L (240 +/- 45 mg/dL) (P less than .001). The goal cholesterol was reached in 22 of 37 patients (59.4 percent), but was maintained in only 7 of 37 (18.9 percent). Nineteen of 37 patients on diet plus niacin also received probucol. Goal cholesterol was reached in 14 of 19 patients (73.6 percent), and was maintained in 11 of 19 (57.9 percent).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339319 TI - Psychotropic drug prescriptions for nursing home residents. AB - Previous work has indicated that psychotropic medications may be misused in nursing homes. Utilizing data from the National Nursing Home Study Pretest, this analysis examined the frequency, indications, and appropriateness of psychotropic drug prescriptions for a random group of 526 US nursing home residents. One third of the sample residents were receiving a psychotropic medication, and 8 percent were receiving more than one. Twenty-one percent of those without a listed mental disorder diagnosis received psychotropic medications, almost one third of which were antipsychotic medications. With no corresponding notation of a related symptom or diagnosis in the chart, 30 percent of 212 psychotropic prescriptions were judged inappropriate by a three-physician panel. Although more research should be done, these results suggest the need for better and more careful charting in nursing homes as well as better training for primary care physicians in the proper prescribing of psychotropic drugs. PMID- 3339320 TI - Psychopathology masquerading as food allergy. AB - Three patients who presented with vague symptoms previously diagnosed as food allergy are reviewed. No evidence for allergy to foods was found in any of the patients. Two were depressed with psychotic thinking and the third had moderately severe anxiety with depression. All three improved following psychiatric diagnosis and intervention. One was treated with antidepressant and one with antidepressant-antipsychotic medication. All three maintained improvement two years later. The diagnosis of food allergy must be based on showing a direct relationship between the inciting food and the immunologically mediated reaction. Anxiety and depression may masquerade as food allergy. Evidence of psychopathology should be present to make such a diagnosis. PMID- 3339322 TI - Hospital privileges for family physicians: documentation of family practice residents' experiences in training. AB - This report describes a study of the content and uses of the University of Washington Affiliated Residency Network documentation system for future hospital privileges. The selected procedures and problems considered important to document for future hospital privileges were validated by means of a graduate survey conducted in 1985. Fifty percent of the 43 graduates responding used their personal documentation when applying for hospital privileges. Intermediate-sized hospitals of 50 to 199 beds were significantly more likely to require documentation than either small (fewer than 50 beds) or large (more than 200 beds) hospitals. However, 84 percent of the hospitals where graduates are located either require documentation or would find it helpful for privilege application. The three-year cumulative experiences of the 1986 cohort of graduating residents are also presented. Thirty-six of the residents (71 percent) participated actively in the voluntary network documentation system. None of the items selected as important to document for future hospital privileges were recorded by 100 percent of the residents. Obstetric procedures and problems were the items most commonly documented. PMID- 3339321 TI - Obstetrics in family practice in the state of Ohio. AB - Two hundred eighty-two active members of the Ohio Academy of Family Physicians responded to a survey questionnaire regarding the content of obstetrics in their practices. Factors that may influence physicians to discontinue obstetrics were also evaluated. Sixty respondents (21 percent) were performing vaginal deliveries in 1987. Only 45 (16 percent) planned to continue delivering babies beyond 1989. Family physicians who started practice within the past seven years were less likely to include obstetrics in their first year of practice than those who began practice prior to 1980. To those physicians who have eliminated obstetrics from their practice in the past five years, fear of litigation and increasing malpractice insurance costs were significantly more important issues than to their colleagues who had stopped doing obstetrics prior to 1976. Every year fewer family physicians choose to provide care to their obstetric patients. The results of this study suggest that only with changes in the medicolegal and liability environments will obstetrics continue to be a part of family practice in Ohio. PMID- 3339323 TI - Acute fatty liver of pregnancy associated with maternal and fetal metabolic acidosis. PMID- 3339324 TI - Attrition from obstetrical practice among family practice residency graduates. PMID- 3339325 TI - Is routine influenza immunization indicated for people over 65 years of age? An affirmative view. AB - Influenza is usually a minor, self-limiting illness, but for the elderly, especially the elderly who have chronic illnesses, it may be a severe or fatal disease. During influenza epidemics this disease may not always be recognized clinically as influenza but may appear as an acute decompensation in a patient with a known chronic illness. The influenza vaccine is not perfect, but it has been shown to be effective in the elderly. Reactions to the vaccine are usually minor and administration costs are low. Experience with influenza vaccine since the early 1940s has led to an improved, more pure vaccine formulation, has developed worldwide systems of tracking the dominant circulating viral strains, and has refined recommendations for vaccine usage based on clinical studies of its efficacy and cost effectiveness. Physicians should be aware of the present limitations of the existing studies and the imperfections of the vaccines, but in the elderly population, a proven intervention that will offer a substantial degree of protection during the influenza season should not be withheld. Most of the existing evidence suggests that the vaccine is effective and that physicians should be more stringent in their influenza immunization practices with the elderly. The elderly who are at high risk should be of high priority for receiving influenza vaccine, and the vaccine should also be recommended to healthy individuals aged 65 years and older because of its proven efficacy for reducing attack rates when appropriate viral strains are used. PMID- 3339326 TI - Is routine influenza immunization indicated for people over 65 years of age? An opposing view. AB - It is true that persons aged over 65 years have greater morbidity and mortality from influenza. This increased morbidity and mortality, however, is mostly the result of a higher prevalence of other chronic diseases in the elderly. There is no evidence that vaccination, even in epidemic years when the antigenic match of the influenza strain and the vaccine is good, benefits the 60 percent of the noninstitutionalized population over the age of 65 years who do not have other high-risk diseases. In fact, the grade II-3 evidence cited by the US Preventive Services Task Force actually supports not immunizing this population group. Even among high-risk patients, the benefit from influenza vaccination is highly variable and difficult to demonstrate. In some years there will be little influenza, and little benefit will accrue; in other years the vaccine-influenza antigenic match will not be good, and little benefit will be obtained. In a few years (two of the 12 years during which Barker's studies were done), a reduction in morbidity can be demonstrated for high-risk elderly persons. Even then, vaccine efficacy is only about 33 percent. Patients are telling physicians that they do not feel influenza vaccination is worthwhile. Less than 25 percent of high-risk persons are vaccinated annually. Many of those vaccinated do so because they falsely believe influenza vaccination will prevent the common cold. In accordance with the ACIP recommendation, high-risk patients with concomitant chronic disease (priority 1) should be immunized, because at least some benefit can be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339327 TI - The purification of four respiratory syncytial virus proteins and their evaluation as protective agents against experimental infection in BALB/c mice. AB - The fusion (F) glycoprotein, large glyco- (G) protein, phospho- (P) protein and 22K protein of respiratory syncytial (RS) virus A2 strain were purified by a combination of immunoaffinity adsorption and preparative SDS-PAGE. All four proteins elicited serum antibody in mice after repeated inoculation in adjuvant, although the magnitude of the response as measured by ELISA varied from mouse to mouse. The F protein generated neutralizing antibodies in only 50% of the mice determined to be seropositive by ELISA. The G protein also induced neutralizing antibodies but in this instance neutralization tests and ELISA titres were more closely correlated. No neutralizing activity was detected in mice immunized with the P or 22K proteins although all produced antibody detectable by ELISA. Mice immunized with either the F or the G protein were found to be protected against subsequent RS virus challenge, whether they had developed neutralizing antibody or not. Mice inoculated with the P or 22K proteins were not protected. PMID- 3339328 TI - Kinetics of synthesis and phosphorylation of respiratory syncytial virus polypeptides. AB - The kinetics of synthesis of [35S]methionine-labelled respiratory syncytial virus specific proteins were studied in CV-1 cells infected at high multiplicity. Immunoprecipitated viral proteins resolved by SDS-PAGE were quantified by scanning fluorographs of protein bands. The nucleocapsid (N) protein was detectable by 2 h post-infection (p.i.), whereas the phospho- (P), matrix (M) and fusion (Fo) proteins and Vp24 (a matrix-like protein) were first detected between 4 and 6 h p.i. Synthesis of the glyco- (G) protein was first detected at 6 h p.i. and reached its peak synthesis rate at 10 h p.i. Virus-specific P, M and Vp24 proteins were phosphorylated in infected cells. The P protein was highly phosphorylated in purified virions whereas phosphorylated species of the M and Vp24 proteins were minor components. The phosphorylated form of the P protein was detected by monoclonal antibody precipitation, confirming the identity of this protein. The N protein was not phosphorylated in infected cells or in virions. Synthesis of [35S]methionine-labelled proteins preceded detectable 32Pi labelling by several hours. The putative phosphorylated M protein was detected at 6 h p.i. before phosphorylated forms of P and Vp24 were seen. The timing of appearance of the phosphorylated species of P and Vp24 proteins in infected cells corresponded to the release of infectious virions from infected cell monolayers at 10 to 12 h p.i. PMID- 3339329 TI - Morphogenesis of yellow fever virus 17D in infected cell cultures. AB - The morphogenesis of yellow fever virus replication was examined in infected Vero cell cultures. Penetration and uncoating occurred by endocytosis with the formation of coated vesicles, similar to that demonstrated for other enveloped and unenveloped viruses. Inclusion bodies associated with newly formed nucleocapsids were evident in the perinuclear region during the growth cycle. No evidence of RNA synthesis in the vicinity of the inclusion bodies was obtained by autoradiography, suggesting that genome replication and assembly of viral nucleocapsids occur at separate cytoplasmic sites. An excessive proliferation of membrane-bound organelles involving both vacuoles and endoplasmic reticula was the most striking feature of virus-infected cells late in infection. No morphological changes in the appearance of nuclei or mitochondria were detected. Virus release appeared to occur by movement of nascent virions through the proliferated endoplasmic reticula followed by exocytic fusion of virus-containing vesicles with the plasmalemma. A possible mechanism whereby the internal nucleocapsid acquires an outer envelope is discussed. PMID- 3339330 TI - Canine parvovirus: strain difference in haemagglutination activity and antigenicity. AB - Canine parvovirus (CPV) strains were compared for haemagglutination (HA) activity and antigenicity and were divided into two types by HA activity. Strains Cp49 and 29-F showed temperature-dependent HA, like feline panleukopenia virus (FPLV) and mink enteritis virus (MEV), whereas strains Sp-80 and Y-1 showed temperature independent HA with erythrocytes from eight species of animals. The results of a cross HA inhibition test using immunized rat sera suggested that of the two types of CPV those showing temperature-dependent HA were antigenically like FPLV and MEV whereas those showing temperature-independent HA were not. This antigenic difference between the two types was confirmed by a HA inhibition test with monoclonal antibodies. A chronological survey revealed that CPV isolates from earlier years have HA activity and antigenicity similar to those of FPLV and MEV, whereas current CPV isolates do not. There are some exceptional isolates from the transitional period which have similar antigenicity to FPLV and MEV but different HA activity. These results suggest that the haemagglutinin of CPV altered from one form resembling that of FPLV to a somewhat different structure during passage in dogs in nature. PMID- 3339331 TI - Nucleotide sequence of the 3' ends of the double-stranded RNAs of grapevine chrome mosaic nepovirus. AB - Attempts were made to label the termini of dsRNAs corresponding to the two genomic RNAs of grapevine chrome mosaic nepovirus (GCMV). It was not possible to label the 5' ends of the dsRNAs with [gamma-32P]ATP, which suggests that a genome linked protein blocks their 5' ends. Both dsRNA species were labelled at their 3' ends with pCp. The 3'-terminal sequences were determined by 'wandering spot' or by partial enzymic cleavage analysis. One strand (presumably positive) ended in a poly(A) 30 to 50 nucleotides long whereas the other (presumably negative) ended in 3'-ACCUUUUAAAAAG (RNA1) or 3'-ACCUUUUAAUAAAG (RNA2). The sequences resemble closely those complementary to the 5' ends of the RNAs of tomato black ring virus (strain S), which is distantly related to GCMV. PMID- 3339332 TI - Production of interferon alpha by dengue virus-infected human monocytes. AB - Human monocytes appear to be very important in the pathogenesis of dengue infection. They are thought to be the most active sites of virus replication during dengue infection. We have analysed interferon (IFN) production by dengue virus from peripheral blood mononuclear cells (PBMC). IFN activity was first detected at 12 h after infection of monocytes and reached a maximum level by 48 h. Non-adherent PBMC depleted of monocytes did not produce detectable levels of IFN, and did not contain dengue antigen-positive cells after exposure to dengue virus. The IFN produced was characterized as IFN-alpha by neutralization tests using specific antisera to HuIFN-alpha, HuIFN-beta and HuIFN-gamma, and by radioimmunoassay. The culture fluids of dengue virus-infected monocytes, which contained IFN-alpha, were able to inhibit infection of human monocytes by dengue virus. These results suggest that IFN-alpha produced by dengue virus-infected monocytes may play an important role in controlling primary dengue virus infection. PMID- 3339333 TI - Identification of haemagglutinin-neuraminidase antibody binding sites by Western blot analysis of antibody-resistant mutants and partial digest fragments of Newcastle disease virus. AB - A collection of monoclonal antibodies (MAbs) which react with the haemagglutinin neuraminidase (HN) protein of Newcastle disease virus (NDV) has been used to isolate MAb-resistant mutants of the Beaudette C strain of NDV. The patterns of cross-reactivity of the HN proteins of these mutants against the collection of MAbs determined by Western blotting allowed the MAbs to be sorted into different groups. Protease V8 partial digest fragments of purified wild-type virions and subsequent reaction against the collection of MAbs using Western blotting provided an alternative method of grouping MAbs which broadly agreed with the former method. Chemical cleavage of the HN protein at aspartate-proline bonds followed by Western blotting of the fragments allowed the approximate position of certain MAb binding sites to be determined. PMID- 3339334 TI - Detection of mononuclear cells expressing hepatitis B virus in peripheral blood from HBsAg positive and negative patients by in situ hybridisation. AB - In situ hybridisation was used to detect RNA of Hepatitis B virus (HBV) in peripheral mononuclear blood cells. Presence of HBV-RNA was detected in 10/17 HBsAg positive HBeAg positive patients, in 8/18 HBsAg positive HBeAg negative patients, in 1/3 anti-HBs positive subjects. Four control subjects were negative. The frequency of labelled cells varied from 1 to 10% of mononuclear cells. These results indicate that the DNA detected so far in mononuclear blood cells may be transcriptionally active. PMID- 3339335 TI - Ethiopian National Hepatitis B Study. AB - A nationwide seroepidemiological study of hepatitis B markers prevalence was conducted in Ethiopia on 5,270 young males from all regions of the country. Overall prevalence rates were 10.8% for HBsAg and 73.3% for "at least one marker positive"; a remarkable geographical and ethnic variability of marker prevalence was observed, reflecting the wide differences existing in Ethiopia in sociocultural environment and activities such as tribal practices and traditional surgery. Sexual practices and medical exposure also play some role as determinants of hepatitis B marker prevalence in Ethiopia. General preventive measures, with particular reference to health education, by affecting incriminating habits and practices could have some impact on infection rates in Ethiopia, in the absence of a vaccination strategy presently unrealistic in this region of the world. PMID- 3339337 TI - A case of metastatic carcinoma in association with Paget's disease of bone. PMID- 3339336 TI - Traumatic occupational occlusive arterial disease of the hands. PMID- 3339338 TI - A community medicine program in Jamaica for fourth year medical students. PMID- 3339339 TI - Combat-related posttraumatic stress disorder. Patterns of symptomatology in help seeking Vietnam veterans. AB - Sixty-one Vietnam veterans who had sought outpatient psychological services were evaluated for posttraumatic stress disorder (PTSD) during two independent diagnostic interviews. Data were analyzed from only those 48 subjects for whom the two diagnoses agreed upon the presence or absence of PTSD. Subjects were administered the Symptom Checklist-90-R, a modified version of the Impact of Event Scale, and two measures of combat stress: the Combat Scale Revised and the Vietnam Experience Scale. Some support was generated for the reliability and validity of the PTSD construct as outlined in DSM-III. In our sample the diagnosis of PTSD was associated with excessive arousal characterized by anxiety, anger, paranoid ideation, intrusive images, and avoidance of stimuli reminiscent of the traumatic stressor. The findings are discussed in relation to previous studies of combat-related PTSD and studies of traumatically stressed civilians. PMID- 3339340 TI - Subpersonalities with dreaming functions in a patient with multiple personalities. AB - A case report of the hypnotherapy and unusual dream work of a patient with multiple personality disorder is described. Two of his 13 personalities claimed a dream production function. These personalities claimed the ability to organize and create dreams in order to communicate with the host personality. In the course of therapy, clinical data are described that tend to support this claim. The data of this case are then briefly applied to some current models of dream function. Some dream theories with an information-processing and reprogramming emphasis are particularly supported by this case material. PMID- 3339341 TI - Increase in urinary beta-phenylethylamine preceding the switch from mania to depression: a "rapid cycler". AB - beta-Phenylethylamine (PEA), an endogenous amphetamine-like substance, is known to increase central catecholamine metabolism and has been hypothesized to have an etiological importance in affective disorders. A case of a "rapid cycler" who showed increased PEA excretion before the switch from mania into depression was reported. In order to evaluate whether the patient's cycle of moods could be prevented by modulating PEA metabolism, carbidopa (peripheral dopa decarboxylase inhibitor) and safrazine (monoamine oxidase inhibitor) were administered during the manic and depressive periods of the patient, respectively. Carbidopa exacerbated the manic symptoms, although it decreased PEA excretion. Safrazine induced the increase of PEA without any beneficial effect on the depressive symptoms. These findings may suggest that PEA plays the role of a biochemical trigger in the switch mechanism of a rapid cycler, especially in the switch from mania to depression. PMID- 3339342 TI - Temporal lobe epilepsy with ictal ecstatic state and interictal behavior of hypergraphia. AB - The authors describe an epileptic patient with ictal ecstatic experiences and an interictal behavioral change of hypergraphia. The patient had a temporal lobe EEG spike focus in the dominant hemisphere. The ecstatic states can be considered true epileptic auras, i.e., simple partial seizures originating in the temporal lobe or the nearby structures. Hypergraphia in this patient seemed to be related to temporal lobe ictal focus in the dominant hemisphere. PMID- 3339343 TI - Interobserver reliability of a "Standardized Psychiatric Examination" (SPE) for case ascertainment (DSM-III). AB - The authors describe the Standardized Psychiatric Examination (SPE), a new method for conducting psychiatric examinations in both clinical and research settings that preserves the clinical method. The SPE provides a consistent replicable format for eliciting and recording psychiatric history, signs, and symptoms without perturbing the patient-clinician interaction. By means of the SPE, the clinician can formulate diagnoses using DSM-III or ICD-9 criteria and yet generate CATEGO profiles derived from the Present State Examination, 9th edition. Psychiatrists using the SPE demonstrated high interrater reliability in ascertaining individual psychopathological symptoms (Kappa range, 0.55 to 1.0) and in making DSM-III diagnoses (Kappa range, 0.79 to 1.0) among a sample of study subjects (N = 43) drawn from both a psychiatric inpatient population and a large community sample of nonpatients from the Epidemiological Catchment Area (ECA) study. The implications of the SPE for clinical practice and for research are discussed. PMID- 3339344 TI - Morphological and neurochemical effects of diazepam and phenobarbital on selective culture of neurons from fetal rat brain. AB - The responses to diazepam (DZ) and phenobarbital (PhB) were studied in enriched neuronal primary cultures from rat embryo hemispheres. Cells were grown in chemically defined medium and the drugs were added for 3 days to cultures, at pharmacologically active concentrations. Following exposure to DZ or to PhB, morphological changes, such as less prominent neuronal processes, were observed in neurons. It was also shown that each drug reduced the specific uptake of 2 deoxy-D-glucose by the cells and interfered with protein and RNA metabolism. It was concluded that both DZ and PhB might affect, at least transiently, the normal growth of neurons in culture. PMID- 3339345 TI - Pyruvate dehydrogenase activity in osmotically shocked rat brain mitochondria: stimulation by oxaloacetate. AB - Pyruvate dehydrogenase complex activity (PDHC) measured by CO2 release isotopic assay has generally been much lower than activity measured by the spectrophotometric arylamine acetyltransferase assay (ArAT). Decarboxylation of [1-14C]pyruvate was measured in osmotically shocked rat brain cortical mitochondria. Activity is dependent on the concentration of the substrate pyruvate. Activity of 74.6 units +/- 12.3 SD (n = 22) was observed at 4 mM pyruvate (1 unit = 1 nmol pyruvate decarboxylated/min/mg protein). Activity was dependent on added NAD, CoA, and thiamine pyrophosphate, implying increased mitochondrial permeability after osmotic shock. Freeze/thaw with sonication of the mitochondrial preparation reduced PDHC activity to 11.5 units +/- 3.0 SD (n = 4). Oxaloacetate produced a marked stimulation of activity. The optimal assay contained 3 mM oxaloacetate, and without oxaloacetate activity fell to 15.4 units +/- 9.9 SD (n = 8). These studies highlight the importance of optimal substrate concentrations in the CO2 release isotopic PDHC method. Higher PDHC activity is found with intact mitochondria and thus activity values should be interpreted in the light of the presence or absence of intact mitochondria in individual preparations. PMID- 3339346 TI - Developmental pattern for deoxyhypusine hydroxylase in rat brain. AB - Deoxyhypusine hydroxylase catalyzes the formation of hypusine from deoxyhypusine in a precursor form of eukaryotic initiation factor 4D (eIF-4D). The enzymatic activity was examined in mammalian brain homogenates and the results were consistent with the existence of deoxyhypusine hydroxylase levels comparable to those occurring in other mammalian tissues. Interspecies differences in the enzyme distribution were quite limited, with the highest specific activity values observed in cow brain (1.82 units/mg of protein). In the rat the enzyme was found to be unevenly distributed among various brain regions. The parietal cortex contained the highest specific activity (2.1 units/mg of protein). Rat brain deoxyhypusine hydroxylase was mainly present in the postmicrosomal supernatant (81% of the total activity). The highest specific activity (3 units/mg of protein) was observed in the rat brain during the first few days of life. Thereafter the activity started to decline, and continued to do so for 15 days, remaining throughout the rest of life at levels of less than one-half that of newborn. PMID- 3339347 TI - Differentiation-dependent sialylation of individual neural cell adhesion molecule polypeptides during postnatal development. AB - The postnatal sialylation of individual neural cell adhesion molecule (N-CAM) polypeptides by a developmentally regulated sialyltransferase in Golgi-enriched fractions isolated from rat brain is described. The 120-kilodalton polypeptide of N-CAM was found to be sialylated at each developmental age examined. This was in contrast to the 140- and 180-kilodalton N-CAM polypeptides which were only sialylated until postnatal day 10 and from postnatal day 12, respectively. Immunoblotting procedures demonstrated that all N-CAM polypeptides were expressed in the Golgi fractions at each developmental stage examined. The heavily sialylated "embryonic" form of N-CAM was found to be reexpressed at postnatal days 10 and 12, a time coincident with extensive fibre outgrowth. The "embryonic" form of N-CAM incorporated similar amounts of [14C]sialic acid into its constituent polypeptides reflecting the difference in sialic acid to protein ratio, as this form of N-CAM was virtually undetectable in the immunoblots of postnatal material. PMID- 3339348 TI - Comparative study of glial marker proteins in the hypoplastic cerebellum of jaundiced Gunn rats. AB - The behavior of marker proteins of glial cells [alpha-enolase, beta-S100 protein, and glial fibrillary acidic protein (GFAP)] was investigated quantitatively by using enzyme immunoassay systems during the development of cerebellar hypoplasia in jaundiced Gunn rats. A neuronal marker protein, gamma-enolase, was also measured as a reference. At postnatal day 8 corresponding to the early stage of cerebellar damage, the amount of beta-S100 on a protein basis was significantly higher in jaundiced homozygotes (jj) than in control nonjaundiced heterozygotes (j+), whereas no differences in alpha- and gamma-enolases and GFAP were observed between the two groups of rats. At days 15 and 30, which correspond, respectively, to the advanced and late stages of cerebellar damage, the three glial proteins, especially GFAP, were higher and the neuronal protein was lower in the jj rat cerebellum than in the control. These results are consistent with the reported histological observations that neuronal cells are vulnerable and damaged by bilirubin, whereas glial cells seem to be less sensitive. On the other hand, the amounts of beta-S100 and alpha-enolase per cerebellum were significantly lower in jj rats at days 15 and 30, as in the case of gamma enolase, whereas that of GFAP remained at the same level as the control at day 15 and showed a slight but significant decrease at day 30. The possibility is suggested that beta-S100 and GFAP may be available as biochemical indicators of glial cells, especially in the early and advanced stages of cerebellar damage, respectively, but that alpha-enolase is less available. PMID- 3339349 TI - Large-scale, one-step purification of oxidized and reduced forms of bovine brain S100b protein by HPLC. AB - A rapid and simple method, using a reverse-phase column in a HPLC system, has been developed to purify high yields of both oxidized and reduced S100b proteins from a bovine brain S100 protein mixture. The final proteins were characterized by amino acid analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and absorbance and fluorescence spectroscopy. Both S100b subtypes appeared highly purified and differed only by their oxidation state: all four cysteinyl sulfhydryl groups were free in reduced S100b protein whereas two of them gave disulfide bridges in oxidized S100b protein. The stability of the oxidation state of the two isolated subtypes suggests that the two forms were not in rapid equilibrium and probably coexisted in vivo. PMID- 3339350 TI - Ionic requirements for the specific binding of [3H]GBR 12783 to a site associated with the dopamine uptake carrier. AB - At 0 degrees C, when Na+ was the only cation present in the incubation medium, increasing the Na+ concentration from 3 to 10 mM enhanced the affinity of [3H]1 [2-(++di-phenylmethoxy)ethyl]-4-(3-phenyl-2-propenyl)piperaz ine [( 3H]GBR 12783) for the specific binding site present in rat striatal membranes without affecting the Bmax. For higher Na+ concentrations, specific binding values plateaued and then slightly decreased at 130 mM Na+. In a 10 mM Na+ medium, the KD and the Bmax were, respectively, 0.23 nM and 12.9 pmol/mg of protein. In the presence of 0.4 nM [3H]GBR 12783, the half-maximal specific binding occurred at 5 mM Na+. A similar Na+ dependence was observed at 20 degrees C. Scatchard plots indicated that K+, Ca2+, Mg2+, and Tris+ acted like competitive inhibitors of the specific binding of [3H]GBR 12783. The inhibitory potency of various cations (K+, Ca2+, Mg2+, Tris+, Li+, and choline) was enhanced when the Na+ concentration was decreased from 130 to 10 mM. In a 10 mM Na+ medium, the rank order of inhibitory potency was Ca2+ (0.13 mM) greater than Mg2+ greater than Tris+ greater than K+ (15 mM). The requirement for Na+ was rather specific, because none of the other cations acted as a substitute for Na+. No anionic requirement was found: Cl-, Br , and F- were equipotent. These results suggest that low Na+ concentrations are required for maximal binding; higher Na+ concentrations protect the specific binding site against the inhibitory effect of other cations. PMID- 3339351 TI - Phorbol ester inhibition of current responses and simultaneous protein phosphorylation in Xenopus oocyte injected with brain mRNA. AB - The role of protein kinase C activation in a coupling of Ca2+-mobilizing receptors/GTP-binding protein/phospholipase C was examined using Xenopus oocytes before and after microinjection of mRNA purified from rat brains. Under voltage clamp conditions, although the phorbol ester TPA per se never elicited any changes in ionic conductance, chloride current responses of mRNA-injected cells to 5-hydroxytryptamine and acetylcholine (ACh) were suppressed by an 8-min pretreatment of 12-O-tetradecanoyl-4 beta-phorbol-13-acetate (TPA), at nanomolar concentrations. Native ACh response in intact follicular oocytes was also inhibited by the TPA treatment. However, similar current responses triggered by the direct activation of their intracellular signalling pathway with guanosine-5' O-(3-thio)triphosphate or Ca2+ were not affected by TPA. Biochemical analyses indicated that phosphorylation of 33,000- and 45,000-dalton proteins was markedly enhanced by TPA in vivo, and that stimulation of receptors with agonists as well as TPA treatment increased phosphoproteins in the membrane fraction of mRNA injected oocytes. These observations suggest that protein kinase C may switch off the signal transduction from receptors to GTP-binding proteins and may participate in the negative feedback modulation of receptor-operated ion channel responses. PMID- 3339352 TI - Zinc uptake into synaptosomes. AB - Zinc uptake was studied in synaptosomes, isolated by the Ficoll flotation technique, using the radiotracer 65Zn. True uptake of zinc could be discriminated from binding to the outside of the synaptosomes by the absence of accumulation at 0 degree C and the dependency of the rate of uptake on the medium osmolarity. The zinc uptake, studied in the presence of various zinc-complexing agents, showed saturation kinetics when analyzed in terms of [Zn]free, yielding Km = 0.25 microM. The zinc uptake was independent of both ATP and the Na+ gradient. No efflux of zinc could be demonstrated from preloaded synaptosomes due to the formation of insoluble zinc complexes inside the synaptosomes. The results are discussed in terms of the modulation of diverse neurochemical processes by zinc. PMID- 3339354 TI - Role of thyroid hormone and nerve growth factor in the development of choline acetyltransferase and other cell-specific marker enzymes in the basal forebrain of the rat. AB - The effects of treatment with L-thyroxine (subcutaneously 0.3 microgram/g body weight daily from birth, i.e., day 1) and 2.5S nerve growth factor (NGF; intraventricularly 2 micrograms on 1, 3, 5, 7, and 9 postnatal days), separately and together, were studied on the biochemical development of different cell types in the basal forebrain of 10-day-old rats. The development of cholinergic, gamma aminobutyric acid-ergic (GABAergic), and glutamatergic neurons was monitored respectively in terms of choline acetyltransferase (ChAT), glutamate decarboxylase (GAD), and glutaminase activities, whereas glutamine synthetase (GS) and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase) activities were used to judge the maturation of astroglial and oligodendroglial cells. Treatment with either thyroid hormone or NGF from birth significantly increased the expression of ChAT activity in the basal forebrain of neonatal rats. When both agents were administered to the same animal, in agreement with our earlier in vitro findings, the stimulation in ChAT activity was much greater than the sum of the individual effects. In hypothyroid rats, significant effects of NGF at the low doses used were not detectable, although the increase of ChAT activity induced by thyroxine was potentiated by NGF in these animals. Under the present experimental conditions neither thyroxine nor NGF treatment had an appreciable effect on the activities of glutaminase, GS, and lactate dehydrogenase. However, the administration of thyroxine markedly increased CNPase activity in normal rats, whereas in hypothyroid rats the effect on both CNPase and GAD was also significant. Similar elevations in CNPase and GAD activities were not observed after NGF treatment, suggesting that the effect of NGF was specific to the cholinergic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339353 TI - Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer's disease. AB - Excitatory dicarboxylic amino acids previously have been ascribed several functions in the brain. Here their total concentration and proposed neurochemical markers of neurotransmitter function have been measured in brain from patients with Alzheimer's disease (AD) and controls. Specimens were obtained antemortem (biopsy) approximately 3 years after emergence of symptoms and promptly (less than 3 h) postmortem some 10 years after onset. Early in the disease a slight elevation in aspartic acid concentration of cerebral cortex was observed in the patients with AD. A reduction in glutamic acid concentration of a similar magnitude was found. It is argued that this, together with a decrease in CSF glutamine content and lack of change in the phosphate-activated brain glutaminase activity of tissue, reflects an early metabolic abnormality. Later in the disease evidence of glutamatergic neurone loss is provided by the finding that in many regions of the cerebral cortex the Na+-dependent uptake of D-[3H]aspartic acid was almost always lowest in AD subjects compared with control when assessed by a method designed to minimise artifacts and epiphenomena. Release of endogenous neurotransmitters from human brain tissue postmortem did not appear to have the characteristics of that from human tissue antemortem and rat brain. PMID- 3339355 TI - Neuronal localization of specific angiotensin II binding sites in the rat inferior olivary nucleus. AB - Adult male Sprague-Dawley rats were treated with 3-acetylpyridine, a neurotoxin selective for the inferior olivary nucleus. Following treatment, the rats exhibited deficits in locomotor behavior indicative of destruction in the inferior olivary nucleus. The rats were sacrificed 3 weeks later, and the binding of 125I-sarcosine, isoleucine angiotensin II to brain homogenates and slide mounted sections of brainstem was determined. Treatment with 3-acetylpyridine significantly decreased specific 125I-sarcosine, isoleucine angiotensin II binding in homogenates of posteroventral brainstem (containing the inferior olivary nucleus) by approximately 50%. Homogenates of dorsal brainstem and hypothalamus-thalamus-midbrain showed no significant changes in specific binding. Treatment with 3-acetylpyridine did not significantly alter the radioligand binding affinity which was determined in the hypothalamus-thalamus-midbrain. Autoradiographic analysis of 125I-sarcosine, isoleucine angiotensin II binding in the brainstem sections indicated that specific angiotensin II binding sites in the inferior olivary nucleus were virtually eliminated by the 3-acetylpyridine treatment. In addition, a comparatively small, but significant, decrease in specific 125I-sarcosine, isoleucine angiotensin II binding occurred in the solitary tract nucleus/dorsal vagal motor nucleus complex. These results indicate that specific angiotensin II binding sites in the inferior olivary nucleus occur exclusively on neuronal perikarya and/or dendrites. PMID- 3339356 TI - Kinetic characterization of inhibition of gamma-aminobutyric acid uptake into cultured neurons and astrocytes by 4,4-diphenyl-3-butenyl derivatives of nipecotic acid and guvacine. AB - The effects of N-(4,4-diphenyl-3-butenyl) derivatives of nipecotic acid (SKF 89976-A and SKF-100844-A) and guvacine (SKF-100330-A) on neuronal and astroglial gamma-aminobutyric acid (GABA) uptake were investigated. In addition, the uptake of SKF-89976-A was studied using the tritiated compound. All of the compounds were found to be competitive inhibitors of GABA uptake irrespective of the cell type, with Ki values similar to or lower than those of the parent amino acids. Moreover, none of the compounds exhibited selectivity with regard to inhibition of neuronal and glial GABA uptake. In spite of the competitive nature of SKF 89976-A, the compound was not transported by the GABA carriers in the two cell types, because no saturable uptake could be demonstrated. PMID- 3339357 TI - Comparison of 125I-angiotensin III and 125I-angiotensin II binding to rat brain membranes. AB - The binding of 125I-angiotensin III (125I-ANG III) to rat brain membranes was examined and compared with that of 125I-angiotensin II (125I-ANG II). Degradation of each ligand, as monitored by HPLC, was effectively inhibited using fragments of ANG III and ANG II known to have little affinity for angiotensin binding sites. Three classes of 125I-ANG III-binding sites were observed based on affinity (KD = 0.13, 1.83, and 10.16 nM) and capacity (Bmax = 1.30, 18.41, and 67.2 fmol/mg protein, respectively). Two classes of 125I-ANG II-binding sites of high affinity (KD = 0.11 and 1.76 nM) and low capacity (Bmax = 1.03 and 18.86 fmol/mg protein, respectively) were also identified. Cross-displacement studies confirmed that the two highest-affinity 125I-ANG III-binding sites and the 125I ANG II-binding sites were the same. On the other hand, the binding of 125I-ANG III to the low-affinity 125I-ANG III-binding site could not be inhibited with ANG II. These data imply that previously measured differences in the biological potency of cerebroventricularly applied ANG III and ANG II probably do not result from differential binding of these peptides to central angiotensin receptors. PMID- 3339359 TI - pH dependence of histidine affinity for blood-brain barrier carrier transport systems for neutral and cationic amino acids. AB - The effects of pH (3.5-7.5) on the brain uptake of histidine by the blood-brain barrier (BBB) carriers for neutral and cationic amino acids were tested, in competition with unlabeled histidine, arginine, or phenylalanine, with the single pass carotid injection technique. Cationic amino acid ( [14C]arginine) uptake was increasingly inhibited by unlabeled histidine as the pH of the injection solution decreased. In contrast, the inhibitory effect of unlabeled histidine on neutral amino acid ( [14C]phenylalanine) uptake decreased with decreasing pH. Brain uptake indices with varying histidine concentrations indicated that the neutral form of histidine inhibited phenylalanine uptake whereas the cationic form competed with arginine uptake. Since phenylalanine decreased [14C]histidine uptake at all pH values whereas arginine did not, it was concluded that the cationic form of histidine had an affinity for the cationic carrier, but was not transported by it. We propose that the saturable entry of histidine into brain is, under normal physiological circumstances, mediated solely by the carrier for neutral amino acids. PMID- 3339358 TI - Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders. AB - Total muscarinic receptor levels, the levels of the subtypes exhibiting high and low affinity for pirenzepine, and the high- and low-affinity agonist states of the receptor were investigated in hippocampal tissue obtained at autopsy from mentally normal individuals and the following pathological groups: Alzheimer's disease, Parkinson's disease, Down's syndrome, alcoholic dementia, Huntington's chorea, and motor-neurone disease. A moderate decrease in the density of both high-affinity pirenzepine and high-affinity agonist subtypes was found in Alzheimer's disease, whereas a trend towards an increase in the overall muscarinic receptor density was apparent in the parkinsonian patients without dementia, mainly due to an increase in the low-affinity agonist state; the differences between the Alzheimer's disease and nondemented parkinsonian cases were highly significant. As previously reported, the levels of both choline acetyltransferase and acetylcholinesterase were markedly reduced in both Alzheimer's disease and Parkinson's disease--with a greater loss of both enzymes in the demented subgroup of parkinsonian patients. Activities of the cholinergic enzymes were also extensively reduced in Down's syndrome, accompanied by a loss of high-affinity pirenzepine binding. There were no significant receptor or enzyme alterations in the other groups studied. These observations suggest that in the human brain, extensive degeneration of cholinergic axons to the hippocampus, as indicated by a loss of cholinergic enzymes, is not necessarily accompanied by extensive muscarinic receptor abnormalities (as might be expected if a major subpopulation were presynaptic). Moreover, the opposite changes in muscarinic binding in Parkinson's and Alzheimer's diseases may be related to the greater severity of dementia in the latter disease. PMID- 3339360 TI - Choline transport and metabolism in soman- or sarin-intoxicated brain. AB - The metabolism and blood-brain transport of choline (Ch) were investigated in perfused canine brain under control conditions and for 60 min after inhibition of brain cholinesterases by the organophosphorus (OP) compounds soman (pinacolylmethylphosphonofluoridate). Ch and acetylcholine (ACh) in blood and brain samples were analyzed using gas chromatography-mass spectrometry methods. Net transport of Ch was determined by Ch analysis in arterial and venous samples. Unidirectional transport of [3H]Ch was determined using the indicator dilution method. During control perfusion periods of 90 min, net efflux of brain Ch occurred at a rate of 1.6 +/- 0.4 nmol/g/min, and the Ch content of the recirculated perfusate increased 10-fold to approximately 8 microM. Brain Ch content increased in proportion to the increase in perfusate Ch level, but brain ACh was unaltered. Rapid administration of soman (100 micrograms) or sarin (400 micrograms) into the arterial perfusate after a 40-min control period resulted in a greater than 10-fold increase in ACh content in cerebral cortex, brainstem, and hippocampus. The ACh content of cerebellum increased only slightly. The Ch level in all four brain regions studied also increased two- to fourfold above control levels. Ch efflux from brain, however, decreased to 0.2 +/- 0.1 nmol/g/min during the 60 min after OP exposure. Unidirectional influx of [3H]Ch was 0.49 +/- 0.07 nmol/g/min before and did not change significantly 10 or 40 min after OP exposure, thus indicating that the Ch transporter of the brain endothelial cell is not directly inhibited.2+ Based on these results, it is proposed that (a) efflux of brain Ch occurs from the extracellular compartment, which becomes depleted when ACh breakdown is inhibited;(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339362 TI - Subcellular localization and characterization of vasopressin binding sites in the ventral septal area, lateral septum, and hippocampus of the rat brain. AB - [Arg8]-Vasopressin (AVP) has been shown to exert characteristic central physiological actions in the ventral septal area of the rat brain. This study reports the characterization of receptors for AVP in synaptic plasma membranes prepared from the ventral septal area, the lateral septum, and the hippocampus. Binding of [3H]AVP was temperature and time dependent, linearly related to protein concentration, saturable, and specific. Scatchard plot analysis suggested the presence of a population of binding sites in the three brain areas with dissociation constants and maximal binding capacities, respectively, of 1.06 +/- 0.39 nM and 24.0 +/- 7.01 fmol/mg of protein (mean +/- SEM; n = 3 for the ventral septal area, 0.92 +/- 0.13 nM and 47.0 +/- 4.96 fmol/mg of protein (n = 3) for the lateral septum, and 0.91 +/- 0.14 nM and 25 +/- 5.02 fmol/mg of protein (n = 3) for the hippocampus. In all three brain regions, the rank order of potencies of several vasopressin analogs, unrelated peptides, and other compounds for competitive displacement of ligand indicated a receptor with properties resembling those of the V1-like receptor for AVP. These data document the presence of a high-affinity, V1-like vasopressin receptor in the rat ventral septal area for which the pharmacological properties are similar to those previously reported in physiological studies. PMID- 3339361 TI - Acylgalactosylceramides in developing dysmyelinating mutant mice. AB - Acylgalactosylceramides (AGC) from forebrains of normal and dysmyelinating (quaking and shiverer) mice were purified by Florisil column chromatography and preparative TLC. These procedures resolved the AGC on the basis of their Rf values into two main fractions which comigrate with their homologs from rat forebrains. In control animals, AGC were detectable in mouse forebrains from the eighth postnatal day and reached maximal values within 20 days. The same developmental pattern was obtained in dysmyelinating shiverer mice but the AGC content was reduced to approximately 30% of control values. In quaking mutants, the AGC were hardly detected. They were also present in sciatic nerve of normal mice and to a lesser extent in trembler mice. Gas chromatography-mass spectrometry analysis of both ester- and amide-linked fatty acids isolated from AGC of normal and shiverer mice shows that the shiverer mutant AGC display a chemical structure similar to that of normal AGC. AGC constituents of control myelin are reduced by approximately 70% in shiverer myelin, indicating that these molecules can be considered as early markers of oligodendrocyte differentiation. The early arrest of myelinogenesis in the quaking animals and the near absence of AGC are in good agreement with this proposal. Moreover, the reduced amount of AGC in the trembler PNS indicates that AGC could also be early markers for differentiation of the Schwann cell. PMID- 3339363 TI - N6-cyclohexyladenosine inhibits veratridine-stimulated 22Na uptake by rat brain synaptosomes. AB - The effect of the stable adenosine analogue, N6-cyclohexyladenosine, on 22Na uptake by rat brain synaptosomes stimulated by veratridine was investigated. In the presence of N6-cyclohexyladenosine, both the initial rate and the maximum sodium uptake were decreased. The inhibitory effect of N6-cyclohexyladenosine on sodium uptake by synaptosomes after 5 s of incubation with 22Na was concentration dependent, antagonized by 1,3-dipropyl-8-p-sulfophenylxanthine, and attenuated by increasing the concentration of veratridine. The possibility that the adenosine analogue, by activating a xanthine-sensitive adenosine receptor, can operate inhibition of the voltage-dependent sodium channels is discussed. PMID- 3339364 TI - Characterization of neurotensin binding sites in intact and solubilized bovine brain membranes. AB - Analysis of the equilibrium binding of [3H]-neurotensin(1-13) at 25 degrees C to its receptor sites in bovine cortex membranes indicated a single population of sites with an apparent equilibrium dissociation constant (KD) of 3.3 nM and a density (Bmax) of 350 fmol/mg protein (Hill coefficient nH = 0.97). Kinetic dissociation studies revealed the presence of a second class of sites comprising less than 10% of the total. KD values of 0.3 and 2.0 nM were obtained for the higher and lower affinity classes of sites, respectively, from association dissociation kinetic studies. The binding of [3H]neurotensin was decreased by cations (monovalent and divalent) and by a nonhydrolysable guanine nucleotide analogue. Competition studies gave a potency ranking of [Gln4]neurotensin greater than neurotensin(8-13) greater than neurotensin(1-13). Smaller neurotensin analogues and neurotensin-like peptides were unable to compete with [3H]neurotensin. Stable binding activity for [3H]neurotensin in detergent solution (Kd = 5.5 nM, Bmax = 250 fmol/mg protein, nH = 1.0) was obtained in 2% digitonin/1 mM Mg2+ extracts of membranes which had been preincubated (25 degrees C, 1 h) with 1 mM Mg2+ prior to solubilization. Association-dissociation kinetic studies then revealed the presence of two classes of sites (KD1 = 0.5 nM, KD2 = 3.6 nM) in a similar proportion to that found in the membranes. The solubilized [3H]-neurotensin activity retained its sensitivity to cations and guanine nucleotide. PMID- 3339366 TI - Sulfhydryl modification of two nicotinic binding sites in mouse brain. AB - Two distinct binding sites with properties corresponding to those expected for nicotinic cholinergic receptors can be identified in brain by the specific binding of nicotine (or acetylcholine) and alpha-bungarotoxin. The effects of modification of these binding sites by treatment with the disulfide-reducing agent dithiothreitol were examined in tissue prepared from DBA mouse brains. Treatment with dithiothreitol reduced the binding measured with either ligand, and reoxidization of the disulfides fully restored binding. The effects of dithiothreitol treatment appeared to be due to a reduction in the maximal binding of nicotine and to a decrease in the binding affinity for alpha-bungarotoxin. Agonist affinity for the alpha-bungarotoxin binding site was reduced by treatment with low concentrations of dithiothreitol. The nicotine binding sites remaining after disulfide treatment displayed rates of ligand association and dissociation similar to those of unmodified tissue, but treatment of previously unmodified tissue with dithiothreitol accelerated the rate of nicotine dissociation. After reduction, both binding sites could be selectively alkylated with bromoacetylcholine. The results suggest that both putative nicotinic receptors in brain respond similarly to disulfide reduction and that their responses resemble those known for the nicotinic receptor of electric tissue. PMID- 3339365 TI - Sialyllactotetraosylceramide, a ganglioside marker for human malignant gliomas. AB - The ganglioside composition of surgically removed human glioma tissue was shown to differ from that of normal adult brain tissue. First, it contained reduced amounts of the major normal brain gangliosides of the gangliotetraose series. Second, it contained increased proportions of gangliosides not detected in normal brain tissue. One of these was isolated and established as being sialyllactotetraosylceramide 3'-isoLM1. Radioimmunoassay for this ganglioside antigen in human glioma tissue revealed that 14/14 specimens of grades III and IV were positive but only 1/4 of grade II. Normal brain tissue was negative. These results suggest that sialyllactotetraosylceramide is a marker for human malignant gliomas. PMID- 3339367 TI - Regulation of central cholecystokinin recognition sites by guanyl nucleotides. AB - Guanyl nucleotides affected the binding of radiolabeled cholecystokinin (CCK) octapeptide to rodent cortical binding sites. Micromolar quantities of a stable GTP analogue, guanylyl-imidodiphosphate (GppNp), resulted in a plateau where binding was decreased by 30%. In the presence of 25 microM GppNp, binding analysis revealed a decrease in affinity (increase in KD), without an apparent effect on the maximal number of binding sites. Ki values for CCK-related peptides shifted up to 1.6-fold. The rate of peptide association decreased by threefold, and the rapid component of peptide dissociation increased. The collective data suggest that a class of central CCK binding sites is linked to nucleotide regulatory proteins. The evidence is discussed with regard to multiple receptor populations and to possible interconversions between receptor types. PMID- 3339368 TI - Biochemical and autoradiographic study of cerebral protein synthesis with [18F] and [14C]fluorophenylalanine. AB - Fluorine-18-labeled ortho or para isomers of L-fluorophenylalanine were used in double-label experiments together with L-[3H]phenylalanine for amino acid incorporation into cerebral proteins of Mongolian gerbil brain. It was demonstrated by qualitative regional comparison of the 18F and 3H autoradiographic images that L-p-[18F]fluorophenylalanine is incorporated into proteins and exhibits a regional cerebral protein synthesis pattern. To a minor extent, L-p-fluorophenyl[3-14C]alanine and L-o-[18F]fluorophenylalanine are hydroxylated in vivo to form labeled tyrosine or tyrosine analogues that are incorporated into cerebral proteins as well. The advantage and validity of the application of L-p-[18F]fluorophenylalanine with positron emission tomography for noninvasive studies of cerebral protein synthesis in humans are evaluated on the basis of an experimental animal approach. PMID- 3339370 TI - Growth inhibition of cultured human glioma cells by beta-interferon is not dependent on changes in ganglioside composition. AB - This investigation tested the hypothesis that the growth inhibiting effects of human beta-interferon on cultured human glioma cells involves changes in the ganglioside composition of these cells. Four cell lines derived from human malignant gliomas (12-18, U-251 MG, I29-A, 7-24) and two lines from human fetal brain (CHI, CHII) were cultured in the presence and in the absence of human beta interferon (HuIFN-beta), 1,000 units per ml medium for three days before harvesting. Human beta-interferon had an inhibitory effect on growth of glioma but not fetal brain cells. Total ganglioside sialic acid for all cell lines ranged between 3.5 and 13.8 micrograms/10(7) cells (0.6-3.9 micrograms/mg protein). No distinct difference in the amount of total ganglioside per cell was observed between neoplastic and non-neoplastic cells, but the latter had more ganglioside per mg total protein. All cell lines displayed different patterns of gangliosides determined by high performance thin layer chromatography, but there was no distinct difference between glioma and fetal brain cells. Human beta interferon increased the total amount of ganglioside per cell in one fetal brain and two glioma lines, but on a protein basis in only one glioma cell line (I29 A); HuIFN-beta had only minor effects on ganglioside patterns. There was a slight shift towards a greater proportion of structurally simpler gangliosides in both fetal brain and two glioma cell lines exposed to HuIFN-beta, but the reverse occurred in glioma U-251 MG. None of these changes strongly correlated with the degree of growth inhibition due to HuIFN-beta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339369 TI - Patterns of epithelial metaplasia in malignant gliomas. II. Squamous differentiation of epithelial-like formations in gliosarcomas and glioblastomas. AB - Six cases are reported (four gliosarcomas and two glioblastomas) in which the epithelial-like areas of glial anaplasia showed focal squamous cell differentiation, characterized by the development of epithelial whorls, keratin pearls and immunopositivity for cytokeratin. The expression of glial fibrillary acidic protein and the development of squamous metaplasia usually were mutually exclusive. Autopsy findings in two patients and clinical work-up in five failed to disclose a primary extraneural malignancy. It is suggested that squamous differentiation may represent an extreme form of epithelial metaplasia in a malignant glioma. This possibility should be kept in mind in the diagnostic evaluation of such cases, especially in view of the current emphasis on the immunomorphologic demonstration of intermediate filament tumor markers. PMID- 3339371 TI - Experimental intracerebral mass: description of model, intracranial pressure changes and neuropathology. AB - In a rodent model designed to replicate the mass effects of spontaneous intracerebral hemorrhage, we have found that there is little change in intracranial pressure (ICP) with microballoons (25 microliters and 50 microliters in volume) equivalent in size to those lesions which occur with this disorder in man. With larger volumes (100 microliters) there is an increase in ICP which is associated with systemic effects on cerebral perfusion pressure (CPP). Neuropathological evidence of ischemic brain damage was found surrounding the mass in all animals, but this was independent of whether the mass was removed or not. These studies suggest that with a mass that corresponds to the size seen most commonly with spontaneous intracerebral hemorrhage in man, focal ischemic brain damage is produced without reduction in global CPP. PMID- 3339372 TI - Neurofilament antigens in acrylamide neuropathy. AB - After repeated exposure, acrylamide (AC) produces degeneration of distal axons. Because neurons whose axons have been injured (e.g. by axotomy) show alterations in their structural and chemical properties, the present study was designed to differentiate the direct effects of AC intoxication from neuronal responses secondary to axonal injury caused by AC. Rats were given AC as either a single high dose (75 mg/kg), or as daily intraperitoneal injections (30 mg/kg, six days per week for four weeks). Dorsal root ganglia of the fifth lumbar level, L5, were examined using a variety of monoclonal antibodies directed against nonphosphorylated (2-135) and phosphorylated (03-44, 06-17, 07-05) epitopes of 145 and 200 kilodalton neurofilament proteins. In control rats, antibody 2-135 stained axons and neuronal cell bodies; antibodies against phosphorylated epitopes of neurofilaments stained only axons distal to the glomerulus. Following chronic AC intoxication, all three antibodies directed against phosphorylated epitopes of neurofilaments (particularly 07-05) demonstrated intense immunoreactivity in 20-30% of neuronal cell bodies. In addition, the glomerular region of these axons was stained. Electron microscopy revealed many chromatolytic cells containing few neurofilaments. In contrast, a single high dose of AC produced no abnormal staining of neuronal cell bodies at a time when slow axonal transport was impaired. Our findings are compared to those observed following axotomy and to those occurring in aluminum-intoxicated rabbits, two experimental disorders in which altered distributions of phosphorylated filaments have been documented. PMID- 3339373 TI - Topographical and cytological evolution of the glial phase during prenatal development of the human brain: histochemical and electron microscopic study. AB - An ultrastructural analysis of prenatal gliogenesis and neuronal-glial relationships in the developing fetal brain was carried out using reduced osmium and periodic acid-thiocarbohydrazide-silver proteinate to stain selectively the glycogen content of the glial population. Gliophilic neuronal migration was confirmed in the human fetus, with radial glial fibers (RGF) acting as obligatory corridors for neuronal migration in the prospective neocortex and underlying intermediate zone (IZ). With this method, the entire glial phase was differentiated from neuronal elements; this permitted a description of the evolutionary distribution pattern of RGF: in the cortical plate, glial fascicles fully dissociate by 18 weeks gestation, whereas in the IZ, they remain grouped in fascicles until their transformation into astrocytes. The most conspicuous and constant developmental feature observed in the maturing glial cytoplasm between 21 and 30 weeks gestation was a radical enhancement in the abundance and activity of the lysosomal apparatus and autophagic vacuoles observed in the RGF, a cytological basis for the transformation of radial glial cells into astrocytes. These data have implications for the understanding of the ontogenesis of the neocortical vertical modules in the human brain and for the phylogenetic analysis of the vertical cortical units in terms of comparative mammalian anatomy. PMID- 3339374 TI - Wind-chill and the seasonal variation of cerebrovascular disease. AB - The hospital admission rates for patients with specific types of stroke were examined for seasonal variation and correlation with meteorological factors. A seasonal variation in admission rates was found for subarachnoid haemorrhage, thrombo-embolic brain infarction and ill-defined cerebrovascular disease. Overall this seasonality was more strongly associated with the computed chilling effect of the atmosphere than with changes in temperature, humidity or wind speed alone. No seasonal variation was observed for admission rates of intracerebral haemorrhage, transient ischaemic attack or occlusion of precerebral arteries. Intracerebral haemorrhage admission rates exhibited a decrease with time. This evidence suggests that seasonal variation in admission rates exists only for certain pathological types of stroke and this is strongly associated with changes in the chilling effect of the atmosphere. PMID- 3339375 TI - Plasma testosterone in nursing home men. AB - Plasma testosterone (T) was measured at 8-9 a.m. in 44 men chronically institutionalized in a Veterans Administration Nursing Home, and correlated with an extensive clinical data base (including age, diagnoses, drugs, laboratory tests, anthropometric measurements, and mortality during the year after the T analysis). Age averaged 76.4 years (range 60-95). Plasma T was below the lower limit of the normal range for healthy young men (i.e. less than 300 ng/dl) in 46% of the men studied. Samples containing low T (less than 300 ng/dl) also contained subnormal unbound T, but normal concentrations of thyroxine and cortisol. Of the low T samples, 45% contained elevated LH, FSH or both (over 20 mU/ml), and the remaining 55% contained LH and FSH levels below this threshold, these two subgroups representing peripheral and central hypogonadism respectively. Plasma T was significantly (p less than 0.02) correlated in a direct relationship with hemoglobin, serum cholesterol, and the occurrence of seizures. PMID- 3339376 TI - Gout and coronary heart disease: the Framingham Study. AB - The relationship between gout, not associated with the use of diuretics, and the development of coronary heart disease was examined in 5209 subjects originally enrolled in the Framingham Study. Based on 32 years of follow-up, the two year incidence of gout was six times greater in men (3.2/1000) as compared to women (0.5/1000). For both sexes, the incidence of gout showed no clear relationship with age. Among men who never received diuretics, those afflicted by gout, as compared to those without gout, experienced a 60% excess of coronary heart disease (95% confidence limits, 1.1-2.2), primarily attributed to a two fold excess of angina pectoris (95% confidence limits, 1.2-3.1). Although gout was usually associated with other atherogenic risk factors, control of systolic blood pressure, total cholesterol, alcohol intake, body mass index, and diabetes failed to alter the effect of gout on the preceding coronary events in men. For women, there were no significant associations between gout and coronary heart disease. We conclude that gout, unrelated to the intake of diuretics, imparts an additional risk of coronary heart disease in men, unexplained by clinically measured risk factors. PMID- 3339377 TI - Measurement of the clinical status of patients with breast cancer: evidence for the validity of self assessment with linear analogue scales. AB - We have assessed the validity of a method of measurement for describing the clinical status of patients with breast cancer. One hundred and nine patients with breast cancer assigned numerical values to their own state of health using linear analogue scales. We have shown previously that this method of measurement is reliable and corresponds well with other methods of assessment. Validity was assessed in this study by examining the ability of measurements to distinguish between groups of patients who differed either in the presence of metastatic disease or in the treatments they were receiving. All patients completed the same set of 29 linear analogue scales that enquired about the severity of health related problems and symptoms. In general, patients with metastatic disease were clearly distinguished from patients without metastases by their scores on items related to physical function. Patients receiving chemotherapy were distinguished from those not receiving chemotherapy by their scores on treatment related toxicities. Measures of psychological and social health were similar in patients receiving chemotherapy regardless of disease status. These results provide further support for the validity of measurement of clinical status with linear analogue scales scored by patients. PMID- 3339378 TI - Respiratory symptoms and pulmonary function as predictors of 10-year mortality from respiratory disease, cardiovascular disease, and all causes in the Whitehall Study. AB - Relationships between various measures of respiratory impairment and 10-year mortality from chronic respiratory diseases, cardiovascular disease and all causes have been investigated in 17,717 male London civil servants aged 40-64 years. Controlling for age and smoking habits, chronic phlegm production was significantly associated with all-causes and respiratory disease mortality. These associations did not persist after controlling for breathlessness or FEV1 percent predicted. Breathlessness was significantly associated with mortality from respiratory and cardiovascular diseases, and all causes. The associations persisted after controlling for age, smoking habits, employment grade, blood pressure, antihypertensive medication, plasma cholesterol level, diabetes, ECG changes, myocardial ischemia, and FEV1 percent predicted. Anti-hypertensive medication, myocardial ischemia and breathlessness showed the strongest associations with cardiovascular disease mortality. FEV1 less than 65% predicted was significantly associated with mortality from respiratory and cardiovascular diseases, and all causes; for the latter two, the rate ratios were not as high as those for breathlessness. PMID- 3339379 TI - The reliability of the maternal memory in a retrospective assessment of nutritional status. AB - This study raises the question of the validity of conclusions based on recalled data by testing the maternal ability to report vital events on her newborn infant after 8 years. First, the retrospective information given by the mother was compared to the prospective data collected immediately after birth. Second, the validity of statistical analyses based on retrospective data was discussed. A dispersion model was used and discrepancies were found between the two sets of data collected in two different ways on the same subjects. It was concluded that the use of retrospective information can lead to false results in regression analyses and could invalidate comparisons in case-control studies because of the difference in variability between cases and controls. PMID- 3339380 TI - Assessment of generalized lymphadenopathy in AIDS research: the degree of clinical agreement. AB - The degree of clinical agreement amongst different physicians on the presence or absence of generalized lymphadenopathy was assessed in 32 randomly selected participants from a prospective study of male sexual contacts of men with AIDS or an AIDS-related condition (ARC). Three physicians completed the same standard examination that was developed for the main project and conducted the examination of the anatomic regions in the same order on each person, at approximately the same time, and in random order. One physician (Doctor A) was the physician responsible for conducting examinations on the main cohort from which these participants were selected. Intra-observer agreement was assessed by comparing Doctor A's examinations on these participants with those he had recently conducted within a one and a half month period in the main study. Acceptable levels of intra-observer agreement (kappa = 0.72) and interobserver agreement (kappa = 0.66) were demonstrated for the presence or absence of generalized lymphadenopathy for Doctor A and Doctor B, a physician who periodically replaced Doctor A in the main project. Agreement between Doctors A, B, and C, was less satisfactory (kappa of 0.45 and 0.39, respectively). Doctor C was the least experienced with the standardized examination. However, during the progress of this study, agreement between the three doctors improved (kappa values for the latter 16 participants ranged from 0.60 to 0.86) suggesting that experience with the criteria and the standardization of the examination may enhance agreement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339381 TI - Clinical assessments as predictors of one year survival after hospitalization: implications for prognostic stratification. AB - In clinical trials measuring the short term survival of patients, prognostic stratification is important to avoid susceptibility bias. Demographic and disease specific clinical features are commonly used to established similarity, but these may not insure prognostic comparability. To identify the generic predictors of one year survival after hospitalization, a cohort of 559 patients admitted to the medical service at New York Hospital was studied. Among all of the clinical and demographic information available at the time of admission, only three were independent predictors of the time until death: functional ability, severity of illness and extent of comorbid disease. The overall one year survival rate was 66%. Six subgroups composed of patients with different combinations of the predictors of prognosis had mortality rates ranging from 97% to 14%. Illness severity was a predictor only in the less functional patients, and only severe comorbidity was associated with a decreased survival after taking into account functional ability and illness severity. Prospective estimates of severity of illness, functional ability and extent of comorbidity can be used to stratify a diverse group of patients according to their probability of one year survival after hospitalization. PMID- 3339382 TI - Urban-rural differences in 12 year coronary heart disease mortality: the Puerto Rico Heart Health Program. AB - Preliminary observations of the Puerto Rican population in 1965 indicated that the coronary heart disease mortality rate was lower than in the U.S., and that the rate in rural areas might be less than urban ones because of lower levels of cardiovascular risk factors. This prompted a prospective investigation of 8793 urban and rural men, aged 45-64 years. A 12-year mortality study has been completed with almost total follow-up. After excluding those with known coronary heart disease at baseline, age-adjusted rates for coronary heart disease, sudden, and stroke death are 19-37% higher in urban than rural men. Urban men had higher average blood pressure, cholesterol, glucose, and heart rate and were less physically active than rural men. When urban-rural differences for the known risk factors, including education and alcohol intake, are adjusted for by multivariate logistic regression analysis, no remaining significant urban-rural coronary heart disease mortality differential is present. Thus, it appears that variation in identified risk factors could explain the difference in mortality within Puerto Rico. The presence of unidentified protective factors cannot be excluded. PMID- 3339383 TI - The predictive value of resting electrocardiograms for 12-year incidence of coronary heart disease in the Honolulu Heart Program. AB - The predictive value of electrocardiographic (ECG) abnormalities at baseline for subsequent risk of fatal and total coronary heart disease (CHD) was analyzed in a 12-year follow-up of 7682 men in the Honolulu Heart Program aged 45-68 who were free of CHD at baseline. Univariate analysis showed that men with major or minor ECG abnormalities, ST depression, high R wave, T-wave inversion, left ventricular hypertrophy or strain and premature ventricular contractions had considerably higher (2-10 fold) CHD incidence rates than those with normal ECG. When blood pressure, cigarette smoking, body mass index, alcohol use, physical activity, serum glucose, serum cholesterol, serum uric acid, age and years lived in Japan were taken into consideration through multivariate analysis, the ECG abnormalities retained significant associations with fatal and total CHD. This study demonstrated that resting ECG abnormalities were independent predictors of both total and fatal CHD. PMID- 3339384 TI - The need for triage on questions related to efficacy: multiple comparisons and type II errors. PMID- 3339385 TI - Cautions re: study of senile dementia. PMID- 3339386 TI - A proposed standard for monitoring equipment: what equipment should be included? PMID- 3339387 TI - The prevalence of hypoxemia detected by pulse oximetry during recovery from anesthesia. AB - Pulse oximetry was used to assess the prevalence of hypoxemia (arterial oxygen saturation of 90% or less) at various times in the immediate postoperative period: five minutes after arrival, 30 minutes later, and just before discharge. Among 149 inpatients studied, one or more hypoxemic measurements were made in 21 (14%) during their postoperative course. Of 92 outpatients, 1 (1%) was found to be hypoxemic. For inpatients, the prevalence of hypoxemia preoperatively, 5 minutes after arrival in recovery, 30 minutes later, and at discharge was 2%, 4%, 6%, and 9%, respectively. Patient factors associated with a significantly higher prevalence of hypoxemia were obesity (22%), body cavity surgical procedures (24%), age over 40 years (18%), American Society of Anesthesiologists physical status (I, 7%; II, 17%; III, 18%; IV, 100%), duration of anesthesia longer than 90 minutes (18%), and intraoperative administration of greater than 1,500 ml of fluid (20%). Unrecognized hypoxemia in postsurgical inpatients with or without these risk factors is common. Therefore routine monitoring of these patients with a pulse oximeter is suggested. PMID- 3339388 TI - A quantitative evaluation of the Hewlett-Packard 78354A noninvasive blood pressure meter. AB - Oscillometrically determined brachial artery pressures were compared with simultaneous contralateral radial intraarterial pressures in 19 anesthetized adult cardiac surgical patients throughout their surgical procedures, interrupted only by nonpulsatile, low-pressure, low-flow cardiopulmonary bypass. Radial intraarterial pressure values ranged widely for systolic (55 to 207 torr), mean (43 to 141 torr), and diastolic (26 to 106 torr). Both error specification methods proposed by the Association for the Advancement of Medical Instrumentation were used and compared. As expected, error method 1 gave consistently lower mean errors, smaller error standard deviations, and higher correlation coefficients than did error method 2. The errors during time periods immediately before and after cardiopulmonary bypass were compared with those from more quiescent times. Higher mean errors, larger error standard deviations, and lower correlation and regression coefficients were found during those time periods surrounding cardiopulmonary bypass. In general, mean errors were lowest for systolic pressure, followed by mean and diastolic pressures in that order, whereas error standard deviations were smallest for mean pressure, followed by systolic and diastolic pressures. Correlation and regression coefficients were highest for systolic pressure, followed by mean and diastolic pressures. In summary, the oscillometric method provides convenient and reproducible estimates of radial intraarterial pressure during most clinical situations, typically with better accuracy than the auscultatory Korotkoff method. The accuracy and reproducibility are diminished during those periods immediately surrounding cardiopulmonary bypass, perhaps due to direct surgical manipulation of the heart with its attendant rapid changes in cardiac output and blood pressure. PMID- 3339389 TI - A clinical evaluation of the accuracy of the Nellcor N-100 and Ohmeda 3700 pulse oximeters. AB - Two pulse oximeters, the Nellcor N-100 and the Ohmeda 3700, were compared with arterial blood values and with each other in a clinical evaluation of performance. Three hundred twenty-nine simultaneously sampled blood/oximeter data pairs from use of both makes of pulse oximeters on each of 152 test subjects were included in the comparison analysis for each oximeter. Among the patients, disease type and severity and hospital location varied widely. Basic descriptive statistics and linear regression analysis were employed to facilitate comparison. Both oximeters displayed a statistically significant but clinically insignificant bias when compared with arterial blood oxyhemoglobin: -0.31 (P = 0.023) and 0.59 (P = 0.001) for the Ohmeda 3700 pulse oximeter and the Nellcor N-100 pulse oximeter, respectively. Relative to arterial blood oxyhemoglobin, the 95% tolerance intervals were +4.84 to -5.45 (10.3) for the Ohmeda 3700 and +6.94 to 5.76 (12.7) for the Nellcor N-100. Regressed against [oxyhemoglobin + carboxyhemoglobin + methemoglobin] as x, the Nellcor N-100 read y = 0.85(x) + 12.5, r = 0.83, P less than 0.0001, and the Ohmeda 3700 read y = 1.02(x) - 5.3, r = 0.86, P less than 0.0001. PMID- 3339391 TI - Evaluation of a microcomputer-based clinical laboratory data acquisition system linked with a minicomputer-based patient data management system. AB - We describe a microcomputer-based clinical laboratory data acquisition system linked with a minicomputer-based patient data management system and report on its performance. The system consists of a microcomputer and six laboratory analyzers: a blood gas analyzer, a flame photometer, a plasma osmotic pressure meter, a chloride ion titrator, a blood sugar analyzer, and a hemoglobin concentration and saturation meter. With the addition of a previously developed microinterface unit to each laboratory analyzer, data from each analyzer can be automatically transmitted to the microcomputer through a communication network. These data are then automatically transmitted to the patient data management system and thereby become part of that data base. Performance of this system was evaluated in two ways: (1) by comparing the turnaround time from an anesthetist's order for a laboratory analysis to receipt of the analysis with the time required in a control situation and (2) by comparing the number of steps a laboratory technician is required to walk to obtain and deliver the laboratory result with the number of steps required in a control situation in which no system was used. The turnaround time and the number of steps walked using this system were 552 +/- 41 seconds (n = 19, P less than 0.001) and 197 +/- 31 steps, respectively (n = 19, P less than 0.001), contrasted with 622 +/- 52 seconds and 374 +/- 87 steps without the system. PMID- 3339390 TI - Automated charting of physiological variables in anesthesia: a quantitative comparison of automated versus handwritten anesthesia records. AB - Eight physiological variables--tidal volume, breathing rate, end-tidal carbon dioxide fraction, oxygen fraction in the anesthetic circuit, oxygen saturation by pulse oximetry, systolic and diastolic blood pressure, and heart rate--recorded on-line by a commercially available automated system were compared with the same variables recorded on handwritten anesthesia records. We quantified the differences between the automated and handwritten records generated from the same 30 patients (2,412 minutes of general anesthesia for elective eye surgical procedures). Considering the design of the study, we claim that the differences between both records were caused by the incompleteness or inaccuracy of the handwritten records, except in two instances. The amounts of missing or erroneous data for these eight physiological variables were expressed as fraction ("error fractions") of the time being recorded, designated EFm and EFe, respectively. For the first five variables the EFm on the handwritten records ranged between 0.23 and 0.31, and the EFe ranged between 0.01 and 0.06. For the last three variables the EFm range was 0.08 to 0.13, and the EFe range was 0.05 to 0.11. Most of these missing or erroneous data occurred during the period of induction (first 15 minutes) and at the end of the case (last 10 minutes). The EFm and EFe during induction had increased to 0.62 and 0.26, respectively, and to 0.76 and 0.06, respectively, at the end of the case. Erroneous data were observed on the automated records for the tidal volume during induction (EFe = 0.0044) and for the oxygen fraction during maintenance (EFe = 0.0024). The effect of averaging by the recordkeeper is discussed. The results of this study indicate the clinical relevance of automated record keeping. PMID- 3339393 TI - The status of plasma therapy as cancer treatment. PMID- 3339392 TI - Evaluation of the Datascope ACCUSAT pulse oximeter in healthy adults. AB - Arterial hemoglobin oxygen saturation measured with the Datascope ACCUSAT pulse oximeter was compared with simultaneous arterial hemoglobin oxygen saturation measurements in healthy adult volunteers. One hundred thirty-five arterial blood samples ranging in saturation from 63 to 100% were obtained from 15 adults, aged 20 to 43 years. These subjects had different skin pigmentation, hematocrit, and smoking habits. Steady-state hypoxia was achieved by varying the inspired oxygen concentration between 10 and 21%. Readings from the Datascope ACCUSAT pulse oximeter and the Hewlett-Packard 47201A ear oximeter were compared with arterial blood samples analyzed by the Instrumentation Laboratories IL 282 in vitro CO Oximeter. The equation for the best fitted linear regression line between the ACCUSAT pulse oximeter and the reference IL 282 CO-Oximeter was: ACCUSAT = 1.08(IL) - 6.86. The linear regression analysis revealed a high degree of correlation (r = 0.99), and a small standard error of the estimate (SEE = 1.29%). Simultaneous comparisons between arterial hemoglobin oxygen saturation measured with the ACCUSAT pulse oximeter and the Hewlett-Packard ear oximeter also showed a close correlation (r = 0.99, SEE = 1.47%). A similar comparison between the ACCUSAT and the Ohmeda 3700 pulse oximeter revealed good correlation (r = 0.99, SEE = 1.72%). We found that the ACCUSAT pulse oximeter is an accurate instrument for measuring arterial hemoglobin oxygen saturation noninvasively in the range between 60 and 100%. PMID- 3339394 TI - Chemotherapy following surgery for stages IE and IIE non-Hodgkin's lymphoma of the gastrointestinal tract. AB - Twenty-six patients were treated with chemotherapy following surgery for gastrointestinal non-Hodgkin's lymphoma (GI-NHL). The median age was 50 years (range, 20 to 76). The primary site included stomach (16 patients), small bowel (seven), large bowel (two), and mesenteric nodes (one). Following surgery, nine patients had macroscopic and four patients had microscopic residual disease, and 13 were felt to have had complete surgical resection. Thirteen patients were stage I and 13 were stage II. Sixteen patients were treated with COPP (cyclophosphamide, vincristine, procarbazine, prednisone), nine with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and one with CVP (cyclophosphamide, vincristine, prednisone). At a median follow-up of 50 months (8+ to 178+ months) ten of 12 stage I patients and nine of 14 stage II patients remain alive. Of the nine patients with macroscopic residual disease, four died of disease 6.5 to 11.0 months after diagnosis, and five are alive 8+ to 178+ months from diagnosis. Fourteen of the remaining 17 patients who had complete surgical resection are alive without disease. Death in the other three patients was due to multiple abdominal abscesses at 12 months, adenocarcinoma of the colon at 57 months, and dementia and progressive neurologic dysfunction at 65 months. No patient who had complete resection has relapsed or developed systemic disease after chemotherapy. These results suggest that complete surgical resection is an important prognostic factor and that chemotherapy without irradiation in completely resected localized GI-NHL can prevent local and systemic relapse resulting in long-term disease-free survival. PMID- 3339395 TI - Emergency laparotomy for spontaneous intestinal and colonic perforations in cancer patients receiving corticosteroids and chemotherapy. AB - Thirty patients with lymphoma (12), leukemia (two), myeloma (one), or metastatic solid tumors (15) were explored for 31 episodes of spontaneous intestinal perforation during an 11-year period at Memorial Sloan-Kettering Cancer Center. Twenty-three patients (76.6%) were receiving corticosteroids alone or in combination with chemotherapy and seven patients (23.4%) were receiving chemotherapy alone at the time of perforation. Fourteen perforations (45%) occurred in the small intestine and 17 perforations (55%) occurred in the colon. Malignancy was histologically demonstrated at the site of perforation in 16 patients (52%). Twenty major postoperative complications occurred in 15 patients (50%) and the operative mortality rate was 53%. Factors such as age, sex, duration or type of symptoms, site of perforation, malignancy at the site of perforation, peripheral leukocyte count, and serum albumin and total protein levels were not significantly related to patient survival. Early diagnosis and aggressive surgical intervention is essential to improve survival following intestinal perforation in this high-risk population. PMID- 3339396 TI - Patterns of failure in primary testicular non-Hodgkin's lymphoma. AB - Patterns of failure were analyzed in 30 patients with testicular non-Hodgkin's lymphoma: 16 had stage IE disease, ten had stage IIE, and four had stage IV. After orchiectomy, two of the 16 patients with stage IE disease received no additional therapy, one received multiagent chemotherapy, and 13 received pelvic and para-aortic radiation. Twelve patients with stage IE disease had progression, and the median time to progression was 12 months. Of the 14 patients with extratesticular involvement (stage IIE or IV), one (stage IV) received no treatment after orchiectomy, three (stage IIE) received para-aortic and pelvic radiation, and ten (seven stage IIE and three stage IV) received multiagent chemotherapy with or without radiation. Eight of the patients with stage IIE or IV disease had progression, and the median time to progression was 11 months. Widespread extranodal progression was observed in 17 of the 20 patients who had progression. The tendency of testicular lymphoma for early systemic progression suggests a need for multiagent chemotherapy in initial management. PMID- 3339397 TI - The prognostic importance of tumor size in malignant gliomas: a computed tomographic scan study by the Brain Tumor Cooperative Group. AB - The prognostic importance of tumor size was studied in 510 patients with malignant glioma (80% with glioblastoma multiforme) in the Valid Study Group of Study 80-01 of the Brain Tumor Study Group (now the Brain Tumor Cooperative Group [BTCG]). The endpoint was length of survival from randomization, which occurred within 3 weeks of definitive surgery. Following randomization, patients were scheduled to receive radiotherapy (RT) (6,020 cGy) during a 7-week period, along with continuing courses of chemotherapy. Computed tomographic (CT) scan information was available for 124 patients preoperatively, 300 patients postoperatively (preradiation), and 218 patients 9 weeks post-RT (+/- 3 weeks). Tumor size was determined as area (length x width) on the contrast-enhanced scan and survival was compared by log rank statistics. Preoperative tumor area was unrelated to survival (P = .48), but postoperative area was significantly prognostic (P less than .0001); the smaller the residual tumor, the longer the patient lived. Patients with a 75% or greater resection, as determined by measuring the difference between the preoperative and the postoperative scans, tended to have better survival, but the difference was not significant (P = .16). The post-RT area was strongly related to survival (P less than .00001). The percent change in area between the pre- and post-RT scans was also prognostic. Tumor size was of prognostic importance independent of the other known prognostic variables: age, Karnofsky performance score, and whether the tumor was glioblastoma or anaplastic astrocytoma. We conclude that the amount of tumor remaining after surgery is an important baseline variable at the start of RT, and that the tumor size 9 weeks following RT is also prognostic. Surgical resection is most important when it leaves the least amount of residual tumor. PMID- 3339398 TI - Recombinant human tumor necrosis factor administered as a five-day continuous infusion in cancer patients: phase I toxicity and effects on lipid metabolism. AB - Recombinant human tumor necrosis factor (rH-TNF) is a cytotoxic monokine with pleiotropic effects. A phase I trial of rH-TNF was initiated using a five-day continuous intravenous (IV) infusion repeated every 28 days. Thirty-eight courses of therapy were administered to 19 patients. The starting dose was 5 X 10(4) U/m2/d, with escalations to 1.0 X 10(5), 2.0 X 10(5), 2.4 X 10(5), and 3.0 X 10(5) U/m2/d. Systemic side effects, including fever, chills, hypotension, fatigue, anorexia, and headaches, were mild and self-limiting. At the maximum tolerated dose of 3.0 X 10(5) U/m2/d, dose-limiting hematologic toxicity was manifested by transient thrombocytopenia and leukopenia. Elevated bilirubin levels were also seen at the higher dose levels. Lipoprotein analysis demonstrated that the five-day treatment with rH-TNF was associated with decreases in high-density lipoproteins, as well as increases in triglycerides and very-low-density lipoproteins. Pharmacokinetic studies using an enzyme-linked immunosorbent assay (ELISA) test indicated plasma rH-TNF levels less than 0.2 U/mL. The recommended phase II dose of rH-TNF administered as a five-day continuous infusion is 2.4 X 10(5) U/m2/d. PMID- 3339399 TI - Surgical controversies in melanoma. PMID- 3339400 TI - Rational for "eight-in-one" chemotherapy. PMID- 3339401 TI - Buspirone attenuates synaptic activation of hippocampal pyramidal cells. AB - The actions of 5-hydroxytryptamine (5-HT) and buspirone, an anxiolytic agent that displays high and selective affinity for 5-HT1A receptor sites, on synaptic activation of hippocampal CA1 pyramidal cells were studied in vitro. Whereas 5-HT application leads to a rapid hyperpolarization and decreased input resistance in pyramidal cells, buspirone has no measurable effects on membrane potential and input resistance. However, unlike 5-HT, buspirone application leads to a gradual and reversible reduction in excitatory postsynaptic potentials (EPSPs) elicited by stimulation of afferents in the stratum radiatum. Concurrent with this attenuation of the EPSP, buspirone decreases the excitability of afferent fibers in the stratum radiatum as evidenced by conduction slowing, increased refractory period, and decreased ability to generate repetitive impulses. 5-HT has no measurable effect on the afferent fibers. The attenuation of the EPSPs and the decrease in afferent fiber excitability appear to be independent of 5-HT receptors as 5-HT neither shares nor antagonizes the effects of buspirone. Thus, both 5-HT and buspirone can contribute to reduced spike activity in pyramidal cells, but they do so via different mechanisms: 5-HT hyperpolarizes pyramidal cells whereas buspirone attenuates their synaptic activation, possibly via action on the presynaptic fibers in the stratum radiatum. PMID- 3339402 TI - Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: studies in the ventral tegmental area. AB - Extracellular single-cell recording and microiontophoretic techniques were used to characterize the effects of cocaine on the activity of mesoaccumbens A10 dopamine (DA) neurons in the rat ventral tegmental area (VTA), which have been implicated in the rewarding effects of this and other drugs of abuse. Because cocaine inhibits the reuptake of DA, norepinephrine (NE), and serotonin (5-HT), and exerts local anesthetic actions, the possible involvement of each of these various mechanisms in the effects of cocaine on A10 DA neurons was investigated. Intravenous administration of cocaine caused a significant, dose-dependent, partial inhibition (50-70%) of the firing of antidromically identified mesoaccumbens DA neurons. Similar partial inhibition of A10 neurons was observed following intravenous administration of nomifensine, GBR-12909, and norcocaine, all of which inhibit DA reuptake. Neither the selective 5-HT uptake inhibitor fluoxetine nor the selective NE uptake inhibitor desmethylimipramine (DMI) inhibited the firing of A10 DA neurons. The local anesthetic agent procaine, which lacks DA uptake blocking efficacy, caused a slight, transient increase in firing rate. These results suggest that the effects of cocaine on A10 DA neurons are due to inhibition of DA reuptake, a conclusion that has been supported by several other findings. Pretreatment with reserpine to deplete vesicular stores of DA significantly reduced the ability of intravenous cocaine to suppress A10 DA neuronal activity. Microiontophoretic administration of cocaine caused only a weak (15-20%) inhibition of the activity of A10 DA neurons, but significantly increased and prolonged the inhibition produced by iontophoretic DA. This effect was not observed with iontophoretically administered procaine iontophoresis of cocaine also significantly potentiated the inhibition of A10 DA activity caused by electrical stimulation of the nucleus accumbens (NAc). Both unilateral ibotenic acid lesions of the NAc and hemitransections of the brain rostral to the VTA significantly reduced the inhibitory effects of intravenous cocaine on A10 DA neurons, suggesting that both somatodendritic impulse-regulating DA autoreceptors and inhibitory NAc-VTA feedback processes are involved in the effects of intravenous cocaine on A10 DA neurons. Therefore, it is hypothesized that the relatively weak inhibitory effects of cocaine on A10 DA neurons may represent a poor compensatory response to enhanced DA neurotransmission within the NAc, and may help to explain the extremely potent rewarding effects of this important drug of abuse. PMID- 3339403 TI - Ganglion cells in the turtle retina contain the neuropeptide LANT-6. AB - This study investigated the presence of the neurotensin-related hexapeptide, LANT 6, in retinal ganglion cells and their central projections in the turtle Pseudemys scripta elegans. Immunocytochemical techniques demonstrated that many of the cells in the ganglion cell layer of the turtle retina could be labeled with an antiserum specific for LANT-6. Radioimmunoassay and chromatographic analysis confirmed the presence of LANT-6-related peptides in retina, as well as brain. Several molecular forms of LANT-6 were observed, some larger than LANT-6. Characterization of the cells labeled in the ganglion cell layer in terms of their cell body size and their dendritic arborization patterns revealed that at least 6 specific LANT-6-positive cell types were present in the ganglion cell layer. Morphologically, the LANT-6-positive cells strongly resembled turtle ganglion cells, as previously described. In addition, two other lines of evidence supported this interpretation. First, double-label studies were performed in which retinal ganglion cells projecting to the tectum were retrogradely labeled by HRP injected into the tectum (using a cobalt chloride color-modified DAB reaction product) and immunocytochemically labeled with DAB using the antiserum against LANT-6. These double-label studies revealed that many of the LANT-6 positive cells in the ganglion cell layer in the portion of the retina labeled retrogradely by the HRP injection did project to the tectum. Within the retrogradely labeled portion of the retina, LANT-6-positive cells that were not labeled retrogradely, as well as neurons labeled retrogradely that did not contain LANT-6 were also observed. Second, the central projections of LANT-6 positive cells of the ganglion cell layer were examined by studying the effects of monocular enucleation on the distribution of LANT-6-positive fibers in the central projection targets of the turtle retina. Two to 8 weeks after enucleation, a substantial reduction in LANT-6-positive fibers was observed in all retinal target areas contralateral to the enucleated eye. Radioimmunoassay and chromatographic studies confirmed the presence of LANT-6-related peptides in the turtle brain and corroborated the reduction of LANT-6 observed in the contralateral tectum following monocular enucleation. Previous studies have demonstrated that LANT-6-related material is present in cells of the ganglion cell layer in a variety of vertebrates. The present results indicate that LANT-6 is in ganglion cells and that it may play a role in neurotransmission between retinal ganglion cells and their central target areas. PMID- 3339404 TI - Target specificity of neuropeptide Y-immunoreactive cranial parasympathetic neurons. AB - We recently showed that neuropeptide Y (NPY)-like immunoreactivity occurs in subpopulations of neurons in 3 cranial parasympathetic ganglia: the otic, sphenopalatine, and ciliary. The present work identifies the target tissues innervated by cranial parasympathetic NPY-immunoreactive neurons. Plexuses of NPY immunoreactive fibers were observed in the parotid gland, the target of the otic ganglion, and in the intraorbital lacrimal gland and palate, targets of the sphenopalatine ganglion. NPY-immunoreactive fibers of apparent parasympathetic origin innervated glandular acini in all 3 structures and were also present around small blood vessels in the parotid and intraorbital lacrimal glands. These fibers were presumed to be parasympathetic because they were not affected by removal of the superior cervical ganglion and because their distribution was coextensive with that of vasoactive intestinal polypeptide (VIP) immunoreactivity, which we have previously shown to be colocalized with NPY in the cell bodies of otic and sphenopalatine ganglion neurons. In contrast, no NPY immunoreactive fibers were observed in the iris or ciliary body of acutely sympathectomized rats, suggesting that NPY-immunoreactive neurons in the ciliary ganglion do not normally transport detectable levels of NPY to their terminals. The target specificities of cranial parasympathetic NPY-immunoreactive neurons are different from those of sympathetic NPY-immunoreactive neurons. Sympathetic NPY-immunoreactive fibers innervated the iris and ciliary body, and the blood vessels but not the parenchymal cells of all the glands examined. In contrast, parasympathetic NPY-immunoreactive fibers primarily innervated glandular acini. NPY-immunoreactive neurons in the sphenopalatine ganglion displayed an additional level of specificity in their projection pattern in that they innervated only a subset of the ganglion's array of target glands: they innervated the intraorbital lacrimal gland and the seromucous glands of the palate but not the exorbital lacrimal gland or the glands of the nasal mucosa. The finding that NPY immunoreactivity is present in the parasympathetic innervation of secretory acini in several craniofacial glands raises the possibility that NPY plays a role in the parasympathetic control of glandular secretion. The observed overlap in the distributions of NPY- and VIP-immunoreactive fibers in these glands further suggests that NPY may interact with VIP to stimulate secretion. PMID- 3339405 TI - Color constancy in the honeybee. AB - A multicolored display was illuminated by 3 bands of wavelengths corresponding to the maxima of the spectral sensitivities of the 3 types of photoreceptors found in the bee retina. The intensity of each band could be varied individually. The light fluxes emitted by the colored areas of the multicolored display were determined quantitatively. Free-flying honeybees were trained with sugar solution to choose one of the colored areas. The illumination was then changed in such a way that the light fluxes formerly emitted by the training area were now measured on another area. When the trained bees were tested under those conditions, they still chose the training area. The relative positions of the colored areas were changed in order to exclude learning of position. It is concluded that color vision in bees is, in a certain range, independent of the spectral content of the illumination. Model calculations show that the behavior observed in bees is consistent with the retinex theory (Land, 1977), i.e., an algorithm using long range interactions is required to explain color constancy. PMID- 3339406 TI - The pharmacology of synapses formed by identified corticocollicular neurons in primary cultures of rat visual cortex. AB - Primary cultures of neurons from the visual cortex of 7-10-d-old Long Evans rats were used to study the pharmacology of synaptic transmission. Dissociated cells were grown either in mass cultures, which contained 8000-10,000 neurons, or in miniature island cultures of 50-100 cells. Prior to dissociation, cells in layer V of visual cortex that project to the superior colliculus were labeled in vivo by retrograde transport of fluorescent latex microspheres-a permanent fluorescent marker. After 2 d to 8 weeks in culture, labeled neurons were identified by epifluorescent illumination, and electrophysiological recordings were obtained from a labeled cell and, simultaneously, from a nearby unlabeled neuron in the same field of view. The 2 neurons were stimulated sequentially by current injection and the pharmacology of evoked postsynaptic potentials (PSPs) was investigated. In mass cultures, relatively few pairs of neurons from which we recorded were synaptically connected, although nearly every cell exhibited abundant spontaneous EPSPs and IPSPs. Neurons grown on island cultures generally did not exhibit spontaneous synaptic activity; however, stimulation of one of the cells in a pair frequently elicited a short-latency PSP in the follower neuron. Retrogradely labeled corticocollicular neurons produced only excitatory PSPs in follower cells, while unlabeled neurons were either excitatory or inhibitory. Three antagonists of excitatory amino acid receptors, kynurenic acid, piperidine dicarboxylic acid, and gamma-D-glutamylglycine, completely blocked EPSPs produced by labeled corticocollicular neurons, as well as EPSPs produced by nearly all of the unlabeled excitatory cells. We have previously shown that these compounds block both N-methyl-D-aspartate (NMDA)-type and non-NMDA receptors on cultured cortical neurons (Huettner and Baughman, 1986). The specific NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) did not alter short-latency EPSPs recorded in 1 mM Mg2+, but did reduce longer-latency EPSPs polysynaptic activity. Since responses mediated by the NMDA receptor are known to be antagonized by Mg2+ (Mayer and Westbrook, 1985), we perfused cultures with Mg2+ free medium and found that the falling phase of some monosynaptic EPSPs was prolonged. Addition of APV to Mg2+-free medium reduced the duration of the falling phase of EPSPs such that they returned to the time course obtained in 1 mM Mg2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3339407 TI - Protein-synthetic machinery beneath postsynaptic sites on CNS neurons: association between polyribosomes and other organelles at the synaptic site. AB - Previous studies have demonstrated that polyribosomes are selectively positioned beneath postsynaptic sites on CNS neurons. In spine-bearing neurons, these polyribosomes are selectively localized at the base of the spines, and occasionally within spine heads. The present study evaluates whether there are relationships between the polyribosomes and other organelles of the postsynaptic cytoplasm, including membranous cisterns and spine apparatuses. Dendritic spines from the dentate gyrus and hippocampus of the rat were analyzed at the electron microscopic level in 2 ways. First, relatively thick sections were prepared for electron microscopy, and spines were photographed in stereo using a goniometer stage. Second, conventional serial thin sections were taken, and spines were reconstructed. From the stereo photographs and serial reconstructions, we determined the proportion of polyribosomes that was associated with membranous cisterns. We also counted the number of ribosomes per cluster to determine whether there were differences between polyribosomes in different intradendritic locations, or between free polyribosomes and polyribosomes on cisternal membranes. From the serially reconstructed spines we determined the incidence of polyribosomes, membranous cisterns, and spine apparatuses, and evaluated the relationships between these organelles. We found that in both the dentate gyrus and hippocampus, about 50% of the polyribosomes that were present beneath the base of spines were associated with membranous cisterns. Polyribosomes that were present in the head of the spine were rarely associated with a cistern, however. The overall incidence of polyribosomes was similar in spines with spine apparatuses and spines without a spine apparatus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339408 TI - Dishabituation and sensitization emerge as separate processes during development in Aplysia. AB - Until recently, dishabituation and sensitization have commonly been considered to reflect a unitary process: Sensitization refers to a general facilitation produced by strong or noxious stimuli that enhances subsequent responding; dishabituation has been thought to represent a special instance of sensitization in which the facilitation is simply superimposed on a habituated response level. The unitary process hypothesis was based on the observation that both decremented and nondecremented responses are facilitated by a common noxious or strong stimulus. However, this observation does not rule out the possibility that dishabituation and sensitization could reflect separate processes that are activated in parallel by a strong stimulus. Recent cellular experiments by Hochner et al. (1986) suggest that this, in fact, occurs in the sensory neurons of the gill withdrawal reflex in Aplysia. A developmental analysis of learning in the marine mollusc Aplysia permits a direct behavioral test of this hypothesis. If dishabituation and sensitization reflect a unitary process then they should emerge at the same time ontogenetically. On the other hand, if they reflect different processes, then they might emerge according to different ontogenetic timetables. In the present study we examined the temporal emergence of dishabituation and sensitization in the defensive siphon withdrawal reflex in 3 stages of juvenile Aplysia: stage 11, early stage 12, and late stage 12. Animals received one of 2 kinds of training: Dishabituation training, in which the effect of strong tail shock on habituated responses were observed, and Sensitization training, in which the effect of strong tail shock on nondecremented responses was observed. We found that, while dishabituation was present in all stages examined, sensitization did not emerge until several weeks later, in late stage 12. These results were confirmed and extended in a group of animals that were tested twice: first in stage 11, when they showed no sensitization, and again 13 weeks later, in late stage 12, when they then showed significant sensitization. Our analysis of nondecremented responses prior to the emergence of sensitization also revealed an unexpected inhibitory component of tail shock that produces reflex depression. Moreover, there was a clear progression in the net effects of tail shock during development: reflex depression was produced in stages 11 and early stage 12, followed by a transition to reflex facilitation (sensitization) in late stage 12. Finally, when sensitization emerged in late stage 12, the process of dishabituation showed a significant increase compared with previous developmental stages.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3339409 TI - The cellular analog of sensitization in Aplysia emerges at the same time in development as behavioral sensitization. AB - Recent studies examining the development of learning and memory in the gill and siphon withdrawal reflex of Aplysia have shown that different forms of learning emerge according to very different developmental timetables. For example, in the previous paper, Rankin and Carew (1988) showed that, whereas habituation and dishabituation emerge early in juvenile development (in stages 9 and 10, respectively), sensitization emerges at least 60 d later (in late stage 12). This developmental separation of different learning processes provides the opportunity to examine the unique contribution of specific cellular mechanisms to each form of learning. As a first step in this cellular analysis, in the present paper we have examined the development of the cellular analog of sensitization (facilitation of nondecremented EPSPs) in the identified giant neuron R2, which can serve as a monitor of the afferent input in the gill and siphon withdrawal reflex (Rayport and Camardo, 1984). We have found 2 striking parallels between the development of behavioral sensitization and the development of its cellular analog: (1) Behavioral sensitization, produced by tail shock, emerges very late in juvenile development (stage 12), and the cellular analog of sensitization (produced by activation of the tail pathway) emerges by exactly the same late juvenile stage; (2) prior to the emergence of behavioral sensitization, tail shock unexpectedly was found to produce significant reflex depression (Rankin and Carew, 1988), and prior to the emergence of the cellular analog of sensitization, activation of the tail pathway was found to produce significant depression of the synaptic input in the reflex pathway. Thus, the cellular analog of sensitization in the CNS develops and matures in close temporal register with the development of behavioral sensitization in juvenile Aplysia. PMID- 3339410 TI - Circadian clock in cell culture: II. In vitro photic entrainment of melatonin oscillation from dissociated chick pineal cells. AB - The avian pineal gland contains circadian oscillators that regulate the rhythmic synthesis of melatonin. We have developed a flow-through cell culture system in order to begin to study the cellular and molecular basis of this vertebrate circadian oscillator. Pineal cell cultures express a circadian oscillation of melatonin release for at least 5 cycles in constant darkness with a period close to 24 hr. In all circadian systems, light regulates the rhythm by the process of entrainment that involves control of the phase and period of the circadian oscillator. In chick pineal cell cultures we have investigated the entraining effects of light in 2 ways: by shifting the light-dark cycle in vitro and by measuring the phase-shifting effects of single light pulses. A 6 hr advance or delay of a LD 12:12 light-dark cycle produced a corresponding shift in the melatonin rhythm. The phase shifts of the rhythms persisted after transfer to constant darkness, showing that the underlying circadian oscillator was entrained. Photic entrainment of the oscillator was further characterized by measuring the phase-shifting effects of single 6 hr light pulses. Single pulses of light shifted the phase of the circadian oscillator in a phase-dependent manner. Light pulses beginning early in the subjective night delayed the phase of the oscillation 8 hr relative to dark controls. Conversely, light pulses beginning late in the subjective night advanced the phase of the oscillation nearly 8 hr. Thus, photoreceptors within the cell cultures can mediate entrainment of the pineal oscillators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339411 TI - Development of sensitization in the escape locomotion system in Aplysia. AB - The development of several forms of nonassociative learning (habituation, dishabituation, and sensitization) has previously been examined in the gill and siphon withdrawal reflex of Aplysia. In the present study we analyzed the development of one of these forms of learning, sensitization, in a different response system in Aplysia, escape locomotion. A broad range of juvenile stages was examined: stages 10, 11, early 12, late 12, and 13 (early adult). We found that sensitization was completely absent in early developmental stages, not appearing until late stage 12. This stage of development is particularly interesting because it is at this same point that (1) sensitization first appears in the gill and siphon withdrawal reflex (Rankin and Carew, 1987), and (2) the cellular analog of sensitization first emerges in the CNS (the abdominal ganglion) of juvenile Aplysia (Nolen and Carew, 1987). The fact that sensitization emerges synchronously in the escape locomotion system and the gill withdrawal system is striking because the 2 response systems differ markedly in their intrinsic developmental timetables, response topography, and underlying neural circuitry. Thus, the emergence of sensitization in both systems at the same late stage of juvenile development suggests the possibility that a single, unified process during development may be responsible for the simultaneous expression of sensitization. PMID- 3339412 TI - Monoclonal antibodies reveal cell-type-specific antigens in the sexually dimorphic olfactory system of Manduca sexta. II. Expression of antigens during postembryonic development. AB - Two classes of monoclonal antibodies specific to the olfactory system of Manduca sexta have been isolated: the olfactory-specific antibody (OSA), which specifically recognizes many or all olfactory receptor cells (ORCs) in both males and females, and the male olfactory-specific antibody (MOSA), which stains male specific receptor cells (principally or exclusively sex-pheromone receptors present only in antennae of males; Hishinuma et al., 1988). In the investigation reported here, we examined the expression of the antigens during postembryonic development in order to correlate the presence of particular antigens with the status of differentiation of the ORCs or with their acquisition of particular functions. As assessed immunocytochemically, the OSA recognizes certain epithelial cells in the antennal imaginal disk of the fifth-instar larva. Later, during the first 70 hr of adult development, when differentiative cell divisions are occurring in the antennal epithelium to generate ORCs and the other cells that make up olfactory sensilla, no cells are stained. Immediately after this period of mitoses, the OSA immunoreactivity reappears exclusively in the ORCs, which begin to elaborate axons as an early event in their differentiation. On immunoblots, the OSA recognizes specific sets of molecules (distinguished on the basis of their apparent molecular weights): 53,000 and 59,000 Da antigens in the disk epithelial cells in the last-instar larva; 53,000, 59,000, and 66,000 Da antigens in the ORCs from 15 to 60% of metamorphic adult development; and 42,000, 59,000, and 66,000 Da antigens in the ORCs from 60 to 100% of adult development. The MOSA also recognizes a subset of the epithelial cells in the antennal disks in male and female larvae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339413 TI - Synaptic circuitry of physiologically identified W-cells in the cat's dorsal lateral geniculate nucleus. AB - The cat's retinogeniculocortical system is comprised of at least 3 parallel pathways, the W-, X-, and Y-cell pathways. Prior studies, particularly at the level of the lateral geniculate nucleus, have focused on X- and Y-cells. In the present study, we describe the synaptic inputs for 2 geniculate W-cells from the parvocellular C-laminae after these neurons were physiologically identified and intracellularly labeled with HRP. For each of the W-cells, we examined electron micrographs taken from over 500 consecutive thin sections; we reconstructed the entire soma plus roughly 15% of the dendritic arbor and determined the pattern of synaptic inputs to these reconstructed regions of each neuron. In several ways, each W-cell exhibits a similar pattern of synaptic inputs. First, we estimate that each W-cell receives approximately 3000-4000 synaptic contacts, which occur most densely on dendrites 50-150 microns from each soma. Second, axosomatic contacts are extremely rare, and most derive from terminals with flattened or pleomorphic vesicles (F terminals). Third, terminals with round vesicles, large profiles, and pale mitochondria (RLP terminals), which are presumed to be retinal terminals, form only about 2-4% of all synapses onto these W-cells; these synapses occur on proximal dendrites. Fourth, F terminals, which provide roughly 15-20% of all synaptic input to these cells, occupy the same region of proximal dendritic arbor as do the RLP terminals. Fifth, and finally, terminals with round vesicles, small profiles, and dark mitochondria (RSD terminals) provide the majority of synapses along all portions of the dendritic arbor. Compared with geniculate X- and Y-cells of the A-laminae (Wilson et al., 1984), these W-cells are innervated by fewer synapses overall and, in particular, by dramatically fewer synapses from RLP (or retinal) terminals. This paucity of direct retinal input to geniculate W-cells might explain the remarkably poor responsiveness of these neurons to visual stimuli and to electrical activation of the optic chiasm. PMID- 3339414 TI - The extent of polysynaptic responses in the dorsal spinocerebellar tract to stimulation of group I afferent fibers in gastrocnemius-soleus. AB - We investigated the extent of the distribution of polysynaptic connections to the dorsal spinocerebellar tract (DSCT). Recording from a randomly selected population of DSCT units, we found that over 60% responded to maximal stimulation of group I afferent fibers in the gastrocnemius-soleus muscle nerve. Most of the responses had a time course or latency consistent with polysynaptic activation. The extensive distribution of this input into the pool of DSCT neurons suggests that input from muscle nerves in general is widely distributed to these neurons. The results further imply that the DSCT plays a more integrative role in the transmission of information from the hindlimb to the cerebellum than has been previously supposed. PMID- 3339415 TI - Rod photoreceptors dissociated from the adult rabbit retina. AB - Rod photoreceptors have been isolated from the adult rabbit retina using enzymatic and mechanical dissociation procedures; their fine structure, synaptic activity, and long-term viability were examined using conventional electron microscopic, quick-freezing, and cell culture techniques. Freshly dissociated photoreceptors were well-preserved compared to their counterparts in the intact retina. About half of the cells, however, exhibited broad continuity between inner and outer segments. Quick-frozen, freeze-substituted rods differed from chemically fixed cells in 3 respects: (1) there was an increased amount of granular matrix in the cytoplasm, mitochondria, and rough endoplasmic reticulum; (2) branching and anastomosing profiles of smooth endoplasmic reticulum had disappeared from the inner segment; and (3) the number of synaptic vesicles within the spherule was highly variable, in some cases leaving synaptic ribbons completely denuded of their halo of vesicles. Light-adapted, solitary rod cells continued to be synaptically active: their endings were capable of endocytosis when placed in the dark in the presence of extracellular ferritin and tracer was incorporated into vesicles and vacuoles; this uptake was much reduced when the cells were incubated with the tracer in the light. Thus, synaptic vesicle regeneration was stimulated in the dark, suggesting that vesicles underwent exocytosis in the dark. Isolated rod cells adhered poorly to most standard substrates; without proper adhesion, cells deteriorated in 2-4 hr. However, photoreceptors did adhere to glutaraldehyde-fixed Vitrogen gels and could be maintained for over 48 hr on this substrate if kept in a complete medium at 22 degrees C. In contrast, Muller cells adhered quickly to a laminin substrate with their endfoot processes. The differential adhesion properties of Muller and photoreceptor cells may be useful in obtaining pure populations of glial cells or neurons from the adult mammalian retina. PMID- 3339416 TI - Anatomical distribution of the growth-associated protein GAP-43/B-50 in the adult rat brain. AB - GAP-43 (B-50,F1,pp46) is a neuron-specific phosphoprotein that has been implicated in the development and modulation of synaptic relationships. Although most neurons cease expressing high levels of GAP-43 after the completion of synaptogenesis (Jacobson et al., 1986), certain brain regions continue to have considerable amounts of the protein throughout life (Oestreicher et al., 1986); in at least one such area, the phosphorylation of the protein has been linked with the events that underlie synaptic potentiation (Lovinger et al., 1985). In this study, we used the indirect immunoperoxidase method to map the distribution of GAP-43/B-50 in the brains of 8 adult rats with 2 different antibodies: a monospecific, polyclonal antibody prepared in sheep against the purified protein and an affinity-purified IgG prepared in rabbits. Specific immunoreactivity was found primarily in the neuropil and followed a generally increasing caudal-to rostral gradient along the neuraxis. Densest staining occurred in layer I of the cortex, the CA1 field of the hippocampus, and in a continuum of subcortical structures that included the caudate-putamen, olfactory tubercle, nucleus accumbens, bed nucleus of the stria terminalis, amygdala, and medial preoptic area-hypothalamus. In the brain stem, staining was seen in the central gray and in ascending visceral relay nuclei, but was essentially absent in areas related to ascending somatosensory information (e.g., the cochlear nuclei or vestibular complex) and motor control (e.g., nucleus ruber or the motor nuclei of the cranial nerves). Staining in dorsal thalamus was likewise modest in most somatosensory and somatomotor relay nuclei, but dark in certain other structures (e.g., mediodorsal nucleus, lateral complex). This distributional pattern raises the question of whether synapses in all areas containing high levels of GAP-43/B 50 are capable of undergoing functional plasticity, or whether the protein may function in some of these areas in some other capacity (e.g., general signal transduction). PMID- 3339417 TI - Radiation-induced reduction of the glial population during development disrupts the formation of olfactory glomeruli in an insect. AB - Interactions between neurons and between neurons and glial cells have been shown by a number of investigators to be critical for normal development of the nervous system. In the olfactory system of Manduca sexta, sensory axons have been shown to induce the formation of synaptic glomeruli in the antennal lobe of the brain (Hildebrand et al., 1979). Oland and Tolbert (1987) found that the growth of sensory axons into the developing antennal lobe causes changes in glial shape and disposition that presage the establishment of glomeruli, each surrounded by a glial envelope. Several lines of evidence lead us to hypothesize that the glial cells of the lobe may be acting as intermediaries in developmental interactions between sensory axons and neurons of the antennal lobe. In the present study, we have tested this hypothesis by using gamma-radiation to reduce the number of glial cells at a time when neurons of the antennal system are postmitotic but glomeruli have not yet developed. When glial numbers are severely reduced, the neuropil of the resulting lobe lacks glomeruli. Despite the presence of afferent axons, the irradiated lobe has many of the features of a lobe that developed in the absence of afferent axons. Our findings indicate that the glial cells must play a necessary role in the inductive influence of the afferent axons. PMID- 3339418 TI - An identified histaminergic neuron can modulate the outputs of buccal-cerebral interneurons in Aplysia via presynaptic inhibition. AB - We have identified 2 buccal-cerebral interneurons (BCIs), B17 and B18, that appear to be involved in the coordination of feeding behavior in Aplysia. The BCIs have their cell bodies in the buccal ganglion, but send axons to the cerebral ganglion via the cerebral-buccal connectives. The BCIs appear to make monosynaptic connections with neurons in the cerebral ganglion that modulate extrinsic muscles involved in feeding behavior. B17 and B18 are activated antiphasically during a motor program induced by stimulating the esophageal nerve and appear to "read out" different phases of the buccal program to different cells in the cerebral ganglion. B17 and B18 are not necessary, and probably not sufficient, to generate the buccal program. These BCIs, and other cells like them in the buccal ganglion, may be capable of coordinating the activity of the intrinsic muscles of the buccal mass with the activity of its extrinsic muscles, and perhaps with those of the lips, mouth, and tentacles. Identified histaminergic neuron, C2, can modulate the outputs of the BCIs onto their synaptic followers in the cerebral ganglion. Firing of C2 inhibits spiking of the BCIs, probably via cerebral-buccal interneurons. C2 also decreases the size of the EPSP that B17 and B18 evoke in cerebral neuron C4. C2 appears to do so monosynaptically, and it decreases the conductance of C4, ruling out one possible postsynaptic mechanism of action. Variance analysis of the EPSPs evoked by B18 supports the hypothesis that C2 acts presynaptically to decrease the release of transmitter. Applications of histamine to the solution bathing the neuron mimic the effect of firing C2 and reduce the size of the EPSPs B18 induces in C4. The bath-applied histamine appears to act directly on B18, since it elicits a voltage dependent increased conductance hyperpolarization recorded in the soma of B18, and the hyperpolarization persists in a solution in which synaptic transmission has been blocked. Histamine did not produce any marked changes of the duration of a TEA-broadened somatic action potential of B18. To the extent that the soma of B18 reflects the membrane properties of its synaptic terminal region, the data suggest that histamine may produce presynaptic inhibition by hyperpolarizing the synaptic terminal region. PMID- 3339419 TI - Developmental decrease in size of peripheral receptive fields of single chorda tympani nerve fibers and relation to increasing NaCl taste sensitivity. AB - During development in rats, sheep, and humans, the taste system acquires increasing responsiveness to NaCl, compared with a variety of other salts and chemicals. To better understand the neural basis of changes in salt taste responses, we studied receptive field size and response properties of single chorda tympani nerve fibers in fetal, perinatal, and postnatal sheep. Individual fungiform papillae were stimulated electrically with 5 microA anodal current to determine the location and number of papillae in receptive fields. Response characteristics of NH4Cl, NaCl, and KCl were determined for the entire field. Receptive fields were dissected for later histological reconstruction and taste bud identification. Median receptive field size decreased during development. Field sizes in lambs were smaller than those in younger animals. This decrease was accompanied by an increase in the NaCl/NH4Cl response ratio of single fibers and an increase in the proportion of fibers and associated fields that responded with higher frequency to NaCl, compared with NH4Cl. In addition, for fibers across all age groups, receptive field size correlated negatively with the NaCl/NH4Cl response ratio; that is, fields most responsive to NaCl had fewer papillae than those most responsive to NH4Cl. For all fibers, receptive field size correlated with response frequencies to NH4Cl and KCl but not NaCl. For NaCl best fibers, receptive field size correlated with the response frequencies to all 3 salts. There was no relation between number of taste buds in a single fungiform papilla and the response frequency elicited during electrical stimulation of the papilla.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339420 TI - Morphology of chorda tympani fiber receptive fields and proposed neural rearrangements during development. AB - The average number of fungiform papillae in receptive fields of single chorda tympani nerve fibers decreases during development in sheep, and a greater proportion of small receptive fields that are highly responsive to NaCl, compared with NH4Cl, is acquired. To learn whether there also are developmental differences in the number of taste buds within the papillae in mapped receptive fields, we studied the morphology of receptive fields and fungiform papillae, and also counted fibers in the chorda tympani nerve, in fetal, perinatal, and postnatal sheep. Whether defined as the number of fungiform papillae or as the number of taste buds within papillae, receptive fields of chorda fibers decrease developmentally. Initially, however, there is an increase, and subsequently a decrease, in the number of taste buds per field. The differences in field size cannot be attributed to developmental alterations in numbers of fungiform papillae because the total number of papillae on the tongue remains constant. The average number of taste buds per papilla, however, also increases and then decreases, and the increase in perinatal animals is accompanied by the appearance of large, multipored taste buds. Because there is a significant relation between fungiform papilla size and number of taste buds in the papilla, papilla size could be one regulating factor for taste bud number. Furthermore, the number of chorda tympani nerve fibers apparently increases up to perinatal stages and then decreases postnatally, providing another potential regulating factor for the number of taste buds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339421 TI - Effects of training on a spatial memory task on high affinity choline uptake in hippocampus and cortex in young adult and aged rats. AB - The relation of forebrain cholinergic function to learning and memory was explored by identification and characterization of a training-induced change in high-affinity choline uptake (HACU), an index of cholinergic activity. Young adult rats were trained to find an invisible escape platform in a water tank using environmental cues. After 4 d of this place-training (16 trials), hippocampal HACU was significantly reduced relative to that observed in rats trained to find a visible platform (cue-training), even when cue- and place trained rats were yoked for swim time. These place- but not cue-trained rats showed significantly lower hippocampal HACU than did naive rats, and no effect of training was noted after only 1 d of training. Similar results were obtained in parietal cortex. These differential training effects on HACU correspond to previous reports that muscarinic blockade impairs place, but not cue, learning. A further experiment revealed that the decrease in HACU in hippocampus, but not in parietal cortex, occurred only during the acquisition phase of learning and was related to the rate of acquisition for individual animals. Hippocampal HACU in naive young and aged (24-27 months) rats did not differ, but the response of the septohippocampal cholinergic system to training was diminished in the aged rats. Old rats displayed impaired place learning and a corresponding dampening of the training-induced change in HACU. These results suggest that there is a task specific engagement of cholinergic function in young animals that does not occur in behaviorally impaired aged animals, a finding that is consistent with a role for cholinergic dysfunction in memory impairments associated with aging. PMID- 3339422 TI - Fluorescence recordings of electrical activity in goldfish optic tectum in vitro. AB - Optical methods for recording electrical activity in the goldfish optic tectum were evaluated. Tectal slices, with a short section of the optic nerve attached, were stained with a fluorescent styryl dye. Potential-dependent fluorescence changes following optic nerve stimulation were monitored with a photodiode. We found that large optical signals could be obtained. Experimental manipulations of the slice bathing solution permitted us to identify several events that contributed to the optical response, including activity in afferent fibers, excitatory and inhibitory postsynaptic potentials, and presumptive glial depolarizations. These results suggest that voltage-sensitive dyes can provide a useful alternative method for monitoring synaptic responses in the goldfish tectum, and may prove valuable in studying changes in the functional synaptic organization of the tectum following manipulations of the retinotectal pathway. PMID- 3339423 TI - The effect of altered neuronal activity on the development of layers in the lateral geniculate nucleus. AB - The main objective of this study was to examine the role of neural activity in the development of cell layers in the dorsal lateral geniculate nucleus (LGN). We studied this relationship in postnatal tree shrews either by completely blocking retinal ganglion cell activity with TTX or by selectively blocking activity to the developing ON-center LGN layers (1 and 2) with 2-amino-4-phosphonobutyric acid (APB), using unilateral and bilateral eye injections. All manipulations were carried out from birth (P0), when no LGN cell layers are evident, to or past the point when layers are recognizable (i.e., 1-2 weeks). Nissl-stained and cytochrome oxidase (CO)-reacted material was examined for all cases. Our results show that in the absence of activity produced by bilateral TTX injections, interlaminar spaces between cell layers do begin to develop. Retinal afferents, which are segregated at birth, remain segregated, and differential CO staining between matched sets of LGN layers is evident. The normal pace of LGN development, however, is slowed significantly: LGN cells are smaller and interlaminar spaces are narrower than are seen in age-matched controls. Unilateral TTX injections produce similar, but more dramatic and asymmetric, effects on LGN cells, perhaps because cells are at a competitive disadvantage relative to their normally innervated counterparts in cortex. Combining unilateral eye enucleation at P0 with subsequent TTX treatment of the other eye clearly demonstrates that axons from the remaining eye are capable of producing their normal complement of LGN layers. The development of the LGN ON-center layers, 1 and 2, and the interlaminar space between them are more affected by TTX treatment than are the other layers. By contrast, APB eye injections do not selectively affect the development of the ON-center layers, but do result in some slowing of overall LGN development. Taken together, these results suggest that activity of retinal afferents is not essential for initiating interlaminar space formation, but is important for the normal pace of maturation of LGN cell layers. PMID- 3339424 TI - Parallel pathways can conduct visual CS information during classical conditioning of the NM response. AB - Single and combined lesions were made to the lateral geniculate nucleus (LGN), the superficial layers of the superior colliculus (SC), and the pretectal nuclei (Ptc) prior to conditioning of the nictitating membrane (NM) response in rabbit with a visual conditioned stimulus (CS). Due to technical considerations, lesions of the dorsal LGN were accompanied by lesions of the visual cortex, the only output of the dorsal LGN, in order to render the dorsal LGN nonfunctional. Single lesions to any one of the 3 target systems (LGN, SC, Ptc) did not alter the rate of conditioning. Furthermore, double lesions to any 2 of the systems did not prevent conditioning, although LGN + SC lesions significantly retarded acquisition. When all 3 systems were lesioned, however, animals never acquired to the visual CS, although they successfully conditioned to an auditory CS. The results indicate that in rabbit there are parallel visual pathways individually capable of supporting the acquisition of conditioned NM responses. PMID- 3339425 TI - The roles of potassium currents in Drosophila flight muscles. AB - The roles of different K+ currents in regulating the generation and waveform of action potentials in Drosophila dorsal longitudinal flight muscles (DLMs) were examined in current-clamp experiments. In response to depolarizing current, DLMs displayed an initial transient rectification of the electronic potential lasting for up to hundreds of milliseconds. This delay in excitation was followed by oscillations or graded spikes that finally gave way to sharply rising spikes. Previous voltage-clamp studies of DLMs have revealed an inward Ca2+ current and at least three K+ currents: IA and IK, which are voltage-dependent, and IC, which is Ca2+ dependent. IA and IC are early inactivating currents, while IK is a slow, noninactivating current. In mature adults, selective elimination of IA either with Shaker (Sh) mutations or with 4-aminopyridine (4-AP), had no effect on spike duration or on the delay in excitation. In contrast, when IC was specifically eliminated with the slowpoke (slo) mutation, there was no delay before excitation, the amplitude of the spikes was significantly increased, and the spike duration was increased by 10-fold. Similar results were obtained by reducing IC in normal muscle by intracellular injections of EGTA or by use of low Ca2+ saline. Furthermore, DLM spikes evoked in slo by stimulation of the motorneuron were also broadened, suggesting that IC functions in a similar manner during normal flight as in current-clamped muscles. Elimination of IK along with IA and IC in saline containing tetraethylammonium or Ba2+ resulted in further prolongation of the DLM spike. In Ba2+ saline, there was an additional increase in spike amplitude as well. We conclude that in mature adults, IC, rather than IA, plays the major role in repolarization of DLM spikes and in the delay before excitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339426 TI - The roles of specificity and competition in the formation of a laminated colliculogeniculate projection. AB - In the present study, we examined the colliculogeniculate projection in normal adult tree shrews and in adults that were bilaterally enucleated at birth. We injected lectin-conjugated HRP into superficial superior colliculus and then mapped the pattern of anterogradely transported enzyme in the ipsilateral dLGN. In normal adult tree shrews, the results confirm that the colliculogeniculate projection is laminated and terminates predominantly in small-celled layers 3 and 6 and in the interlaminar space between layers 4 and 5 (Fitzpatrick et al., 1980); we report an additional sparse projection to layer 4. In bilaterally enucleated animals, the colliculogeniculate projection is unlaminated and tends to terminate in the lateral two-thirds of the dLGN even though synaptic sites are vacated throughout the nucleus. We suggest that this preference may be due to a specificity of the colliculogeniculate fibers for the lateral two-thirds of the dLGN, which, in normal adult tree shrews, contains cells with similar physiological characteristics. We further suggest that the normal lamination of the colliculogeniculate projection in the lateral two-thirds of the dLGN may be due to competition with retinogeniculate fibers so that colliculogeniculate fibers terminate predominantly in layers containing small, W-like cells. PMID- 3339427 TI - Evidence that the neural pathways involved in backward conditioning are different from those involved in forward conditioning. AB - Effects of forward and backward conditioned-unconditioned stimulus (CS-US) intervals on classical conditioning of the flexion reflex were examined in a spinal cat preparation. A less intense conditioned stimulus (CS) was employed (activation of A-alpha cutaneous fibers) compared to that of a previous study (activation of both A-alpha and A-delta cutaneous fibers). Interstimulus intervals (ISIs) ranging from +3.0 to -3.0 sec were examined in 9 experimental groups, and results contrasted to those of an explicitly unpaired control group. The ISI of -0.25 sec produced optimal backward excitatory conditioning, paralleling the previous results. However, in contrast to the previous study, no conditioning was observed in any of the forward ISI groups. These observations support the hypothesis that backward and forward conditioning may be fundamentally different phenomena, induced by CS activation of different spinal reflex pathways: backward conditioning involves spinal reflex pathways activated by A-alpha cutaneous fibers of the CS, while forward conditioning involves spinal reflex pathways activated by A-delta cutaneous fibers of the CS. PMID- 3339428 TI - Cloning of cDNA for DARPP-32, a dopamine- and cyclic AMP-regulated neuronal phosphoprotein. AB - A cDNA clone for the mRNA of bovine DARPP-32 (dopamine- and adenosine 3',5' monophosphate-regulated phosphoprotein, Mr = 32,000) was isolated from a modified Okayama-Berg plasmid library. Transformed Escherichia coli colonies were screened by in situ colony hybridization with 2 different oligonucleotide probes corresponding to a region unusually rich in glutamate within the protein. Three positive clones were isolated and shown to encode DARPP-32 by an in situ immunoblot assay of their fusion protein products with beta-galactosidase. The results of the sequence analysis of the longest cDNA clone, pTKD7 (1771 nucleotides), revealed a 606-nucleotide-long coding region, in exact agreement with the bovine DARPP-32 amino acid sequence (Williams et al., 1986). Southern blot analysis of total bovine genomic DNA showed that there is a single gene coding for DARPP-32. Northern blot analysis of caudate nucleus RNA using antisense RNA derived from the clone pTKD7 demonstrated the existence of 2 abundant mRNA species, corresponding to 1.8 and 1.65 kilobase in length. The high concentration of DARPP-32 mRNAs in the caudate nucleus is in agreement with the known distribution of this protein. PMID- 3339429 TI - Neuronal populations stained with the monoclonal antibody Cat-301 in the mammalian cerebral cortex and thalamus. AB - The monoclonal antibody Cat-301 was used to examine neurons in the cerebral cortex and dorsal thalamus of several mammalian species, including Old World monkeys, cats, bush babies, guinea pigs, and rats. In each species, subpopulations of cortical and thalamic neurons are stained along the surfaces of their somata and proximal dendrites. Cat-301-positive cortical neurons include specific groups of pyramidal cells (e.g., corticospinal but not corticobulbar or callosal neurons in the monkey sensory-motor areas) and certain GABA immunoreactive nonpyramidal cells. In the thalamus, the relay neurons projecting to the cortex and not the intrinsic neurons are stained. The Cat-301-positive neurons are nonhomogeneously distributed in the cat and monkey cortex and thalamus. In the cortex, they are densely packed in 2 bands that in most areas include layers III and V, but that in primary sensory areas include layers IV and VI. Because the density of stained neurons, their distribution, and the intensity of their staining vary among cortical areas, the borders between neighboring areas can often be detected by the differences in Cat-301 staining. Broader, regional differences are also readily apparent, for areas in the parietal and occipital lobes contain large numbers of intensely stained cells, but most areas in the frontal and temporal lobes contain fewer, more lightly stained neurons. The same broad differences are seen within the thalamus: only those nuclei reciprocally connected with intensely stained cortical areas contain large numbers of Cat-301-positive neurons. Differences among species include variations in cell density and distribution when a given cortical area or thalamic nucleus is compared between cats and monkeys. Greater differences are seen among the other species. Immunoreactive neurons in the cerebral cortex are sparse and lightly stained in guinea pigs, are restricted to the hippocampal formation in rats, and are very rare and isolated in bush babies. Similarly, Cat-301-positive thalamic neurons are restricted to only one or 2 nuclei in the guinea pig and rat and are extremely rare in the bush baby. Cat-301 stains organized groups of neurons in the cat and monkey cortex and thalamus. In addition to the laminar organization of stained cells in all cortical areas (see above), the Cat-301 positive neurons of monkey areas 17 and 18 are grouped into radial arrays. In area 17, clusters of stained cells are present in layers above and below layer IVC. These clusters lie at the centers of ocular dominance columns, within patches stained for cytochrome oxidase (CO). Most of these cells are also GABA immunoreactive.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3339430 TI - Deposition and transfer of axonally transported phospholipids in rat sciatic nerve. AB - Radioactive glycerol, ethanolamine, or choline injected into the vicinity of the cell bodies of rat sciatic nerve sensory fibers is incorporated into phospholipid. Some newly synthesized ethanolamine and choline phosphoglycerides are subsequently committed to transport down the sciatic nerve axons at a rate of several hundred millimeters per day. Most labeled choline phosphoglycerides move uniformly down the axons; in contrast, the crest of moving ethanolamine phosphoglycerides is continually attenuated. These data, as well as differences in the clearance of these phospholipids distal to a nerve ligature, suggest that various classes of labeled phospholipids are differentially unloaded from the transport vector (possibly by exchange with unlabeled lipid in stationary axonal structures) during movement down the axons. The extent of unloading appears to be defined by the base moiety; both diacyl and plasmalogen species of ethanolamine phosphoglycerides exchange extensively with stationary axonal lipids, while most choline phosphoglycerides continue down the axons. Autoradiographic studies with 3H-choline and 3H-ethanolamine demonstrated that most unloaded phospholipid is initially deposited in axonal structures; some of this unloaded lipid is subsequently transferred to the axon/myelin interface (axolemma?) and then to myelin. Although transported ethanolamine phosphoglycerides exchange more extensively with lipids in stationary axonal structures than do choline phosphoglycerides, at early times more label from 3H-choline is found in myelin. A model to resolve this seeming discrepancy is proposed, wherein a differential topographic localization of phospholipid classes in the membrane of the transport vector allows for a preferential extensive exchange of transported ethanolamine phosphoglycerides with lipids in stationary axonal structures, while choline phosphoglycerides become available for rapid transfer to myelin by a process involving vesicle fusion with axolemma. PMID- 3339431 TI - Experimental localization of muscarinic receptor subtypes to cingulate cortical afferents and neurons. AB - A technique was developed to evaluate the potency of ligand binding at M2 ACh receptors and to experimentally localize the M1 and M2 subtypes to specific neuronal processes. Normal and experimental material was prepared with tritiated ligand binding to cryostat-sectioned area 29c of posterior cingulate cortex in rat, coverslip autoradiography, and single-grain-counting techniques. Three fundamental issues were addressed. 1. A morphological criterion termed an index of heterogeneity was developed by which the specificity of M2 binding by different ligands could be assessed. The index was calculated by first determining the laminar distribution of pirenzepine (PZ) binding sites and then summing absolute laminar variations from this distribution for each ligand. According to this measure the most efficient protocol for assaying M2 sites was tritiated oxotremorine-M (OXO) coincubated in unlabeled PZ (5 x 10(-8) M). The classical muscarinic antagonist propylbenzilylcholine mustard (Pr-BCM), however, when coincubated in PZ, was almost as efficient as PZ-blocked OXO binding. 2. Terminal axons of neurons in the anterior thalamic nuclei (ATN) have M2 receptors based on the following observations. First, specific binding of the M1 ligand PZ was unaffected by ATN lesions. Second, tritiated OXO and PrBCM binding blocked with unlabeled PZ, conditions favoring M2 receptor binding, showed significant reductions in binding in layers la, lb, and IV following ATN ablations. Third, IC50 values as determined by competition of PZ for PrBCM binding sites were shifted to lower concentrations in superficial layers by ATN lesions but not in deep layers where the thalamus does not terminate. Finally, in contrast to PZ blocked OXO and PrBCM binding, binding of PZ-blocked 3H-quinuclidinyl benzilate (QNB) was reduced to homogeneity following ATN lesions. 3. Cortical pyramidal neurons have dendritic receptors that are primarily of the M1 subtype but may also include M2 sites. Thus, full depth ibotenic acid lesions reduced PZ binding by almost 70%. Neurotoxin lesions of neurons in layers II-IV or Vb-VI were followed by degeneration of the apical dendrites of pyramids in layer I and 78 and 15% reductions, respectively, in PZ binding. Also, full-depth neurotoxin lesions combined with ATN ablations completely abolished heterogeneities in PrBCM and PZ-blocked OXO binding. These data demonstrate that experimental techniques can be used in conjunction with normal material to make morphological assessments of the efficiency of binding of putative M2 ligands.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3339432 TI - Schwann cell surfaces but not extracellular matrix organized by Schwann cells support neurite outgrowth from embryonic rat retina. AB - Despite evidence that glial cell surfaces and components of the extracellular matrix (ECM) support neurite outgrowth in many culture systems, the relative contributions of these factors have rarely been compared directly. Specifically, it remains to be determined which components of peripheral nerve support growth of central nerve fibers. We have directly compared neurite outgrowth from embryonic day 15 rat retinal explants placed onto beds of (1) Schwann cells without ECM, (2) Schwann cells expressing ECM (including a basal lamina), (3) cell-free ECM prepared from neuron-Schwann cell cultures, (4) nonglial cells (fibroblasts), and (5) 2 isolated ECM components, laminin and type I collagen. From the first day in culture, retinal explants extended neurites when placed on Schwann cells without ECM. Outgrowth on Schwann cells expressing ECM was also extensive, but not obviously different form that on Schwann cells alone. Ultrastructural study revealed that 95% of retinal neurites in ECM-containing cultures contacted other neurites and Schwann cell surfaces exclusively. On cell free ECM prepared from neuron-Schwann cell cultures, neurite extension was poor to nonexistent. No neurite outgrowth occurred on fibroblasts. Retinal explants also failed to extend neurites onto purified laminin and ammoniated type I collagen substrata; however, growth was rapid and extensive on air-dried type I collagen. In cultures containing islands of air-dried type I collagen on a laminin-coated coverslip, retinal explants attached and extended neurites on collagen, but these neurites did not extend off the island onto the laminin substratum. We conclude from these experiments that neurite extension from embryonic rat retina is supported by a factor found on the surface of Schwann cells and that neither organized nor isolated ECM components provide this neurite promotion. These findings are discussed in relation to possible species differences in growth requirements for retinal ganglion cell neurites and to the specificity of response of different CNS neurites to ECM substrata. PMID- 3339433 TI - The ontogeny of inhibition and excitation in the gerbil lateral superior olive. AB - While the development of excitatory responses has been the focus of considerable research, the ontogeny of inhibitory connections has received relatively little attention. The lateral superior olive (LSO), an auditory nucleus in the ventral brain stem, is a favorable system in which to compare the maturation of an inhibitory and an excitatory input. Neurons in the LSO are excited by stimuli delivered to the ipsilateral ear and inhibited by similar stimuli to the contralateral ear. Single-neuron recordings were made to characterize tone-evoked responses at the onset of hearing and in adult Mongolian gerbils. The results indicated that frequency selectivity was significantly poorer in young than adult animals. In several cases, neurons within the same animal were found to have disparate tuning properties, such that one of the units had "adult-like" tuning, while the other was much more broadly tuned. No difference existed between excitatory and inhibitory tuning within any age group. The degree to which the excitatory and inhibitory characteristic frequencies of an LSO neuron were correlated was used as a measure of tonotopic map alignment. A significant improvement of matching was seen with increasing age. A comparison of excitatory and inhibitory thresholds indicated that the inhibitory system was relatively more efficacious in young than adult animals. The ability of LSO neurons to respond to interaural intensity differences, the binaural parameter to which they are sensitive, indicated 3 differences between adult and young animals: the dynamic range was smaller, the slope was shallower, and the sample of neurons encoded a constrained range of interaural intensity difference values. We conclude that the maturation of the inhibitory and excitatory systems are nearly identical. PMID- 3339435 TI - Traumatic dissections of the extracranial internal carotid artery. AB - Traumatic dissections of the extracranial internal carotid artery (ICA) in 18 patients aged 19 to 55 years were studied. All had suffered blunt head or neck injury of marked or moderate severity; motor-vehicle accidents were the leading cause of the injury. Delayed focal cerebral ischemic symptoms were the most common presenting symptoms. Less commonly noted was focal unilateral headache associated with oculosympathetic paresis or bruit. Following a head injury, the abrupt onset of focal cerebral symptoms after a lucid interval should raise the suspicion of arterial injury, particularly when computerized tomography fails to show abnormalities that would explain the evolving neurological deficits on the basis of direct trauma to the brain. Unilateral headaches, oculosympathetic palsy, and bruits also help in establishing the diagnosis. Focal cerebral ischemic symptoms may develop months or years after the initial trauma. These delayed symptoms are caused by embolization from a thrombus within a residual dissecting aneurysm. Common angiographic findings, in decreasing order of frequency, are: aneurysm, stenosis of the lumen, occlusion, intimal flap, distal branch occlusion (embolization), and slow ICA-to-middle cerebral artery flow. Although two patients died as the result of massive cerebral infarction and edema and some were left with severe neurological deficits, most made a good recovery. Residual dissecting aneurysms and occlusion seem to occur more frequently with traumatic dissections than with spontaneous dissections of the extracranial ICA. PMID- 3339434 TI - K-252a: a specific inhibitor of the action of nerve growth factor on PC 12 cells. AB - K-252a, a kinase inhibitor isolated from the culture broth of Nocardiopsis sp., selectively inhibits the actions of nerve growth factor (NGF) on PC 12 cells. At a concentration of 200 nM, K-252a prevents neurite generation initiated by NGF, but not neurite generation produced by fibroblast growth factor or outgrowth produced by dibutyryl cAMP. K-252a also inhibits the induction of ornithine decarboxylase by NGF, but stimulates ornithine decarboxylase induction by epidermal growth factor. Stimulation of phosphatidylinositol breakdown by NGF was similarly inhibited by K-252a, while stimulation by epidermal growth factor was enhanced. The NGF-induced decrease in the phosphorylation of a soluble protein, Nsp 100, was prevented by K-252a. K-252a blocks the NGF-induced heterodown regulation of the epidermal growth factor receptor, but not the epidermal growth factor-induced homodown-regulation of the epidermal growth factor receptor. K 252a, then, provides a new tool for the dissection and study of NGF-requiring processes. PMID- 3339436 TI - Platelet aggregation within cerebral arteriovenous malformations. AB - Turbulence within cerebral arteriovenous malformations (AVM's) may lead to endothelial disruption, platelet aggregation, and thrombus formation. This hypothesis would account for many of the pathological features in AVM's, including intimal hyperplasia and arterial thrombosis with or without organization. In this study, a dual-isotope method employing indium-111-labeled platelets and technetium-99m-labeled red blood cells was used to evaluate in vivo platelet aggregation in 20 patients with AVM's. The use of two isotopes allows subtraction of the blood-pool platelets and calculation of the ratio of the indium deposited:the indium in the blood pool (In(D)/In(BP)). After a 24-hour incubation period, eight of the 20 patients demonstrated platelet aggregation in their AVM's with a mean In(D)/In(BP) ration of 0.71 +/- 0.36 (+/- standard deviation). Seven of these AVM's were available for pathological study and all of them demonstrated evidence of arterial thrombosis of variable age. In the remaining 12 patients, the In(D)/In(BP) ratio was not significantly elevated (mean 0.02 +/- 0.13), indicating the absence of active platelet aggregation during this short interval of study. Five of these AVM's were pathologically examined, four of which showed evidence of arterial occlusion. It is concluded that platelet aggregation is a common occurrence in cerebral AVM's and may account for the dynamic histopathology often seen in these lesions. PMID- 3339437 TI - Myelopathic cervical spondylotic lesions demonstrated by magnetic resonance imaging. AB - Eighteen cases are presented in which magnetic resonance (MR) imaging demonstrated two types of lesions in patients with cervical spondylotic myelopathy. In the first type, localized spinal cord changes at the level of compression, consistent with myelomalacia, were revealed best with T2-weighted images as high-intensity spinal cord signals. In the second type, lesions consistent with either cystic necrosis or secondary syrinx were noted locally, and/or extending longitudinally up, and/or down inside the spinal cord. These latter lesions were best revealed as low-intensity signals on T1-weighted MR images and as a signal-void sign (moving fluid) on proton-density or T2-weighted MR images. It is suggested that segmental lesions at the level of the spondylotic bar represent early proton changes from pressure in and around the same zones that evolve into gray-matter enhancement regions shown as "snake-eyes" on delayed computerized tomography (CT) after myelography. The longitudinal lesions are thought to be the same pencil-shaped zones of cystic necrosis evolving into a secondary syrinx in the late stages (and usually found in the anterior portion of the dorsal columns during delayed CT after myelography). As spinal MR imaging continues to improve, these lesions will be demonstrated more clearly within the cord substance. PMID- 3339438 TI - Odontoid process fracture osteosynthesis with a direct screw fixation technique in nine consecutive cases. AB - The authors present their experience with surgical treatment of odontoid process fractures using a direct screw fixation technique via an anterolateral retropharyngeal approach. Nine consecutive patients have been operated on with this technique. There were two deaths unrelated to the surgery, and anatomical union with conservation of the craniospinal hinge mobility was achieved in the remaining seven patients. The direct screw fixation technique appears feasible, efficient, and logical. PMID- 3339439 TI - Use of etomidate, temporary arterial occlusion, and intraoperative angiography in surgical treatment of large and giant cerebral aneurysms. AB - The operative management of large and giant aneurysms is complicated by their typically atheromatous and thick walls, frequent intramural thrombosis with calcification, and broad-based necks that often incorporate perforating and other vital vessels. Not infrequently, it is necessary to at least focally arrest the intracranial circulation and open or excise these aneurysms to facilitate vascular reconstruction. This maneuver, in patients whose disease processes have destroyed autoregulatory function or who have inadequate sources of anatomical collateral supply, may cause the threshold for permanent ischemic injury to be exceeded. The authors have recently treated 14 such patients while under electroencephalographic monitoring to document electrical burst suppression induced by the administration of etomidate, followed by temporary clipping to permit vascular repair and intraoperative angiography to document patency of parent arteries. Up to 60 minutes of internal carotid artery occlusion, 35 minutes of middle cerebral artery occlusion, 19 minutes of upper basilar artery occlusion, and 4 1/2 minutes of lower basilar artery occlusion have been well tolerated using this protocol. In such situations, etomidate may be effective in protecting the cerebral circulation without the detrimental cardiotoxicity observed with protective doses of barbiturates. PMID- 3339440 TI - Selective sacral rootlet neurectomy in the treatment of detrusor hyperreflexia. Technique and long-term results. AB - Selective sacral neurectomy was performed in 12 patients with intractable urge incontinence of long duration (mean 12 years) caused by detrusor hyperreflexia. There was great variation in the innervation of the bladder, but resection of an S-3 root or rootlet was carried out in all patients. Six of the patients, who were followed for a mean period of 5.8 years, were cured, and symptoms recurred in two patients after 1 1/2 and 2 years. In patients whose detrusor hyperreflexia recurred, the amplitude of the bladder contractions was significantly lower. This treatment appears reasonable in patients with severe intractable voiding dysfunction caused by detrusor hyperreflexia. PMID- 3339441 TI - Physiological support and monitoring of critically ill patients during magnetic resonance imaging. AB - Magnetic resonance (MR) imaging has been largely restricted to patients who are neurologically and hemodynamically stable. The strong magnetic field and radiofrequency transmissions involved in acquiring images are potential sources of interference with monitoring equipment. A method of support and physiological monitoring of critically ill neurosurgical and neurological patients during MR imaging using a 0.6-tesla MR system is reported. This technique has not caused degradation of the MR image due to electrical interference. Adequate preparation and precautions allow many critically ill neurosurgical and neurological patients to safely undergo MR imaging. PMID- 3339442 TI - Partial characterization of a soluble mitogenic factor from medulloblastoma. AB - To determine how medulloblastoma cells might influence the proliferation and phenotype of normal stromal cells, normal human leptomeningeal cells were treated in culture with medulloblastoma-conditioned medium; their ability to incorporate tritiated thymidine and synthesize collagen was measured. The treated leptomeningeal cells had a significantly greater uptake of tritiated thymidine and grew faster than control leptomeningeal cells. Immunofluorescence studies demonstrated a greater intensity of staining for procollagen type III in the cell layer of the treated cultures than in control cultures; diethylaminoethyl (DEAE) cellulose chromatography of the medium showed that the treated cells synthesized predominantly type III collagen, whereas control cells synthesized type I collagen. Analysis of the medulloblastoma-conditioned medium revealed that the soluble factor responsible for these effects in an acid- and heat-stable protein. The increased proliferation and altered collagen synthesis induced in leptomeningeal cell cultures by a soluble factor from a medulloblastoma are examples of how tumor and stromal elements interact, and may be related to the process of desmoplasia often observed in medulloblastomas in vivo. PMID- 3339443 TI - The role of vasopressin in acute cerebral vasospasm. Effect on spasm of a vasopressin antagonist or vasopressin antiserum. AB - An experimental model of subarachnoid hemorrhage (SAH) in the Sprague-Dawley rat induces angiographically demonstrable, reproducible biphasic vasospasm of the vertebrobasilar system. The acute vasospasm is maximum at 10 minutes and the maximum late vasospasm occurs 2 days after the SAH. Brattleboro rats, which are deficient in arginine vasopressin (AVP), do not have acute vasospasm after SAH but exhibit a degree of late vasospasm that is not significantly different from that seen in Sprague-Dawley rats. Cisternal injection of AVP induced acute vasospasm in Sprague-Dawley rats with a duration similar to that seen after cisternal blood injection; however, at 2 days, the vessel diameter was normal. Intravenous AVP antagonist or intracisternal AVP antiserum administered prior to the SAH prevented the development of acute vasospasm without affecting the late phase. The data suggest that an increased release of AVP in the cerebrospinal fluid is involved in the development of acute cerebral vasospasm. PMID- 3339444 TI - Fibrinolytic activity in experimental intracerebral hematoma. AB - In an attempt to investigate the role of tissue fibrinolytic activity in the resolution of intracerebral hematoma, an experimental model of intracerebral hematoma was developed in the rat. The fibrinolytic activity was studied using a histochemical fibrin slide technique. A total of 59 adult male rats were studied. Twenty-nine rats were used for developing the intracerebral hematoma model via injection of autologous whole blood into the left frontal lobe; in the remaining 30 rats, the intracerebral hematomas were studied sequentially. Intracerebral hematoma formation was unsuccessful in six (21%) of 29 rats. Four rats died in the immediate postoperative period and two showed no intraparenchymal clot. Intense fibrinolytic activity was demonstrated in the blood vessel walls of the normal brain, especially in the meninges, choroid plexus, and ependymal cell layer. In the initial stages of hematoma resolution, fibrinolytic activity was not seen in the hematoma or parenchyma except in the preexisting blood vessels. However, 3 to 5 days later, fibrinolytic activity was observed in the capillary buds surrounding the hematoma and among the infiltrating mononuclear cells. This activity increased for 7 to 10 days following formation of the hematoma and decreased after 21 to 28 days. It is concluded that tissue fibrinolytic activity associated with newly formed blood vessels appears to be important in lysis of intracerebral hematomas. PMID- 3339445 TI - Treatment of dural sinus thrombosis with local urokinase infusion. Case report. AB - Current therapy for dural sinus thrombosis consists of supportive measures, anticoagulation therapy, and in some cases intravenous infusion of a fibrinolytic agent. A patient with extensive dural sinus thrombosis was successfully treated with local urokinase infusion. The technique and rationale for this aggressive therapy are discussed. PMID- 3339446 TI - Vein of Galen aneurysm associated with dural AVM and straight sinus thrombosis. Case report. AB - A 64-year-old man presented with symptoms of obstructive hydrocephalus secondary to a vein of Galen aneurysm associated with a dural arteriovenous malformation and straight sinus thrombosis. The interrelationship of these lesions and their clinical and radiological features are discussed. It is proposed that in this case sinus thrombosis was the primary event in the subsequent development of the other lesions. PMID- 3339447 TI - Enterogenous cyst in the cervical spinal canal. Case report. AB - The case of an 11-year-old Japanese girl with an intradural and extramedullary enterogenous cyst is presented. A mass giving a low-intensity signal in comparison with the spinal cord was demonstrated on magnetic resonance imaging. Histologically, the diagnosis was confirmed on specimens stained with periodic acid-Schiff, alcian blue, mucicarmine, and immunohistochemical staining of carcinoembryonic antigen, and by electron microscopy. PMID- 3339448 TI - Stress-induced malignant hyperthermia in a head-injured patient. Case report. AB - Susceptibility to malignant hyperthermia is a rare inherited myopathy. Hypermetabolic crises accompanied by a rise in body temperature to as high as 44 degrees C are the hallmark of malignant hyperthermia episodes. These are triggered by inhalational anesthetic agents or depolarizing muscle-relaxant drugs. A similar condition exists in pigs; however, in addition to drug-induced attacks, episodes of malignant hyperthermia occur in these animals as a result of stress. It has been proposed that stress-induced malignant hyperthermia occurs in man. The present paper presents a case of stress-induced malignant hyperthermia in a 21-year-old man in whom the inciting stress was a head injury. PMID- 3339449 TI - Intrachiasmatic craniopharyngioma: a rare cause of chiasmal thickening. Case report. AB - The authors describe the case of a young man who presented with a central scotoma in one eye and a temporal hemianopsia in the other. Magnetic resonance imaging showed distinctive bilobed thickening of the chiasm and a "potbelly" expansion of the contiguous optic nerves. The distal portions of the intracranial optic nerves appeared normal. At craniotomy, incision of the lamina terminalis exposed intraventricular craniopharyngioma with anterior extension into the chiasm and proximal optic nerves. Partial resection of the tumor restored normal vision. PMID- 3339451 TI - Symptomatic Arnold-Chiari malformations. PMID- 3339450 TI - Primary leiomyosarcoma of the dura mater. Case report. AB - A rare case of leiomyosarcoma arising from the dura mater is presented. A definite histological diagnosis was based on the electron microscopic features. Extensive removal of the tumor and postoperative radiation therapy resulted in complete remission. The etiology and the origin of this tumor are discussed. PMID- 3339452 TI - Cauda equina syndrome following chemonucleolysis. PMID- 3339453 TI - Epilepsy following ventricular shunt placement. PMID- 3339454 TI - Magnet hospitals: Part I. Institutions of excellence. AB - The oft repeated charge today is "focus on those who are succeeding!" That's what this report does. Using the eight characteristics identified by Peters and Waterman in their book In Search of Excellence (New York: Harper & Row, 1982), the study analyzes 16 magnet hospitals to ascertain to what extent they possessed characteristics similar to the best run companies in the corporate community. Analysis indicates many areas of strong correspondence. The authors suggest that these magnet hospitals may be dealing effectively with the nursing shortage by creating organizational conditions conducive to eliminating internal nurse shortage. PMID- 3339455 TI - Finding the productivity standard in your acuity system. AB - What is a realistic patient workload for nurses to handle on a given shift? Should the workload vary from shift-to-shift and nurse-to-nurse? This article describes how (1) the authors identified the standard inherent in their patient classification system; (2) the system is used to establish department workload standards; (3) managers comply with the established standard; and (4) nursing costs are affected when compliance with the standard is not achieved. PMID- 3339456 TI - Making shared governance work: a conceptual model. AB - Most of the nursing literature offers little substantive rationale for why Shared Governance works or how to evaluate it. This article presents a model of Shared Governance that is based on more than fifty research articles on participation in decision-making. It gives administrators an overview of why Shared Governance impacts satisfaction and organizational commitment. The model should facilitate both designing a Shared Governance system to fit a particular organization and evaluating that system. PMID- 3339457 TI - Killing them softly. PMID- 3339458 TI - The nurse executive defendant. PMID- 3339460 TI - Magnet hospitals: Part II. Institutions of excellence. AB - The oft repeated charge today is to "focus on those who are succeeding!" That's what this report does. Using the eight characteristics identified by Peters and Waterman in their book In Search of Excellence, the study analyzes 16 magnet hospitals to ascertain to what extent they possess characteristics similar to the 'best run' companies in the corporate community. The authors suggest that these magnet hospitals may be dealing effectively with the nursing shortage by creating organizational conditions conducive to eliminating internal nurse shortage. Part I of this article appeared the January 1988 issue of JONA. PMID- 3339459 TI - Building research credibility. PMID- 3339461 TI - Research networking. PMID- 3339462 TI - Social support groups. PMID- 3339463 TI - Research in service settings: Part I--Consortium project outcomes. AB - As nurse executives in today's cost-conscious environment attempt to meet their professional responsibilities for encouraging and supporting staff involvement in nursing research, they may wish to consider strategies similar to those described here. In this unique 3-year project, a consortium of nine health care agencies shared research expertise and resources, with the overall aim of incorporating nursing research into practice. This article reports the outcomes and the authors' assessment of the experience. Part 2 , which will be published in the March issue of JONA will describe the consortium's current focus and program. PMID- 3339464 TI - Preparing nursing administrators. PMID- 3339465 TI - Nursing's precious resource: the clinical nurse specialist. PMID- 3339466 TI - The consultant's image. AB - Nurses provide consultation in various forms and in many different settings. Paramount to the success of these encounters is the initial relationship established between client and consultant. Although the consultation literature discusses the importance of this initial relationship in terms of successful outcome, very little attention has been given to how this relationship may be established. The author explores the impact of dress on establishing this initial relationship in the consultation process. PMID- 3339467 TI - Nurse-midwifery as a career. PMID- 3339468 TI - The relationship between infant feeding method and maternal role adjustment. PMID- 3339469 TI - The clinical nurse-midwife as scientist. PMID- 3339470 TI - Prevention of HIV transmission in health care settings. PMID- 3339471 TI - Effects of beta-carotene and retinyl palmitate on corn oil-induced superoxide dismutase and catalase in rats. AB - The present study was undertaken to determine the effects of beta-carotene on corn oil-induced superoxide dismutase and catalase. Six groups of male Buffalo rats were fed the following diets for 6 wk: a control diet containing recommended levels of beta-carotene and retinyl palmitate, a retinol diet containing 10 times the recommended level of retinyl palmitate, and a beta-carotene diet containing 10 times the recommended levels of beta-carotene and adequate levels of retinyl palmitate. Each vitamin combination was fed with either 5% (wt/wt) corn oil (low fat) or 20% corn oil (high fat). Plasma total beta-carotene levels were highest in the beta-carotene groups. Levels varied inversely with the level of fat in the control group and directly with fat in the beta-carotene group. Transport of beta carotene appeared to parallel that of cholesterol in that 36 and 35%, respectively, were associated with the low density lipoprotein fraction. Accumulation of beta-carotene in the liver was apparent from the observation that levels in liver were much higher than those in plasma. Superoxide dismutase activity was much lower in the beta-carotene groups than in the retinol groups, irrespective of level of fat, and catalase activity was also lower in the beta carotene group, but it was in proportion to the level of fat. These findings suggest that beta-carotene functions as an antioxidant in vivo. PMID- 3339472 TI - Essential role of adenosylcobalamin in leucine synthesis from beta-leucine in the domestic chicken. AB - This study was designed to investigate a postulated relationship between vitamin B-12 and leucine metabolism in mature domestic chickens. Plasma amino acid analysis revealed the presence of beta-leucine at a concentration of 60 to 80 mumol/l. After 425 d on a vitamin B-12-deficient diet, plasma beta-leucine was 133% higher (P less than 0.06) and plasma leucine and methionine lower (P less than 0.03) than values in plasma from hens fed a diet adequate in vitamin B-12. Branched-chain-amino-acid aminotransferase (EC 2.6.1.42) (BCAT) activity was not enhanced by vitamin B-12 deprivation (P greater than 0.05). In contrast to leucine, beta-leucine was not utilized as substrate by BCAT for the formation of alpha-ketoisocaproate. Kidney extracts possessed leucine 2,3-aminomutase (EC 5.4.3.7) (LAM) activity, as evidenced by enhanced conversion of beta-leucine to alpha-leucine in the presence of adenosylcobalamin. LAM activity could not be demonstrated in liver or muscle extract, while leucine formation by pancreas extract was negligible. These data represent the first evidence of the presence of the amino acid beta-leucine in chicken plasma. In addition, the data support vitamin B-12-dependent leucine synthesis from beta-leucine in the chicken and highlight the kidney's role in leucine synthesis. PMID- 3339473 TI - Immature corn as a source of niacin for rats. AB - The variability in the concentration and biological availability of niacin in corn was investigated. Plots of both sweet and field corn were harvested at different stages. In rat growth assays for available niacin, grains harvested at the immature, "milky" stage and then dried gave values of 88 and 74 micrograms/g, respectively. These values were in contrast to the low growth assay values of 18 and 16 micrograms/g for grain harvested at maturity, and even higher than the value of approximately 56 micrograms/g obtained for each immature corn in both the Association of Official Analytical Chemists procedure of chemical analysis and a standard microbiological procedure. However, when the milky grains were precooked at neutral pH, the values from these procedures were higher and agreed with the biological assay results. It is suggested that, during the initial alkaline digestion used for these two procedures, a proportion of the niacin in NAD, the major form of niacin in milky corn, degrades. However, when the materials are first cooked at neutral pH, nicotinamide is released without loss, and the pyridine ring is then stable. The traditional American Indian practice of roasting and drying "green corn" apparently provided a valuable source of niacin. PMID- 3339475 TI - Tissue-specific accumulation of metallothionein in chickens as influenced by the route of zinc administration. AB - The effect of the route of zinc (Zn) administration on the induction of metallothionein (MT) in various tissues of chicks was examined. Four-week-old, male chicks were assigned to one of four treatments: 5 mg Zn/kg intraperitoneal (i.p.) injection, 5 mg Zn/kg intravenous (i.v.) injection, 16 mg Zn oral (O) dose or a saline control (C). Chicks were fasted overnight, treated and killed 24 h later. 109Cd radioassay analysis of liver (L), kidney (K) and pancreas (P) showed a significant elevation of MT in all tissues except K of i.v. chicks. Comparing tissue MT accumulation within treatments showed that L was induced to a greater extent than P for the i.p. treatment (P/L ratio = 0.69 +/- 0.04), while the reverse effect was seen for both O (1.51 +/- 0.10) and i.v. (1.67 +/- 0.14) chicks, reflecting greater P than L accumulation. Zn injected i.p. did not result in significantly greater total peritoneal exudate cell (PEC) or macrophage (M) numbers than saline-injected controls. Sephadex, while causing massive increases in PEC and M, did not induce tissue MT, demonstrating the lack of correlation between PECs or Ms and MT accumulation. Feed intake by chicks during the 24-h period following i.p. Zn treatment was only 30% of that by controls. A subsequent experiment demonstrated that a similar restriction in feed intake increased L but not P MT. This increase accounted for 17.8% of the L induction due to i.p. Zn injection. This does not fully account for the reduction in P/L that is characteristic of i.p. treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339474 TI - Incomplete utilization of pyridoxine-beta-glucoside as vitamin B-6 in the rat. AB - This research was conducted to determine the bioavailability of 5'-O-(beta-D glucopyranosyl) pyridoxine (PN-glucoside) during chronic administration in a depletion-repletion bioassay. PN-glucoside was found previously to constitute a major portion of the total vitamin B-6 in many foods of plant origin. Following a 14-d depletion period, rats were fed diets containing graded levels of either free pyridoxine (PN) or PN-glucoside for 17 d. Slope ratio analysis of dose response curves, on the basis of growth and plasma pyridoxal 5-phosphate (PLP) concentration, indicated 10-34% utilization of PN-glucoside relative to the molar response to PN. Erythrocyte aspartate amino-transferase (AspAT) activity and urinary 4-pyridoxic acid concentration were lower and the stimulation of AspAT activity by exogenous PLP was greater for rats fed PN-glucoside than for those fed PN, which indicated reduced vitamin B-6 nutriture in response to PN glucoside. A constant 7-9% of the ingested PN-glucoside was detected in urine in intact form at all dosage levels. These results provide further evidence of incomplete bioavailability of PN-glucoside and indicate that its extent of utilization is not influenced by its level of dietary intake. PMID- 3339476 TI - Effect of tricarballylic acid, a nonmetabolizable rumen fermentation product of trans-aconitic acid, on Mg, Ca and Zn utilization of rats. AB - trans-Aconitic acid has been implicated in magnesium deficiency of ruminants since the 1960s, but recent experiments indicated that much of it can be converted by rumen bacteria to tricarballylic acid (TCBA). Rats were used as experimental models in the studies described here because analogous experiments in ruminants would have been very expensive. When TCBA was fed to young male Sprague-Dawley rats as 2% of an AIN-76A diet with marginal (200 mg/kg) or adequate (500 mg/kg) Mg, virtually all of the dietary acid was recovered in the urine. Mg and Ca absorptions were unaffected by TCBA but urinary losses of Mg, Ca and Zn were higher than in pair-fed controls. TCBA was highly correlated (r = 0.93) with titratable acid excretion, and Mg, Ca and Zn retentions were reduced by 90, 35 and 56%, respectively. Rats fed 2% citric acid, a structurally similar but metabolizable acid, excreted more Zn than controls but did not excrete excess Mg or Ca. Since TCBA led to a depletion of Mg and other cations, it could be a contributing factor in the etiology of the Mg deficiency known as grass tetany in ruminants. Additional work in ruminants now seems warranted. PMID- 3339477 TI - Developmental changes in response to overfeeding: effect on composition of gain, liver metabolism and adipocyte cellularity in rats. AB - It has been proposed that voluntary food intake limits growth rate. The experiment described here investigated the effects of increased food intake on growth rate. Four age groups of female rats were given either 150 or 100 of ad libitum intake by oral gavage. Animals were tube-fed at these levels of intake for 1 wk. Overfeeding significantly increased carcass weight and fat for all ages examined. Carcass protein was significantly elevated in the overfed animals for the two youngest age groups. Differences between age groups in apparent energetic efficiency were small. Hepatic palmitate oxidation was depressed and esterification increased in all overfed rats. Fat cell size was increased by overfeeding in all age groups. In conclusion, the effects of overfeeding on the four age groups of rats studied were independent of age. PMID- 3339478 TI - Rat transthyretin: effects of acute short-term food deprivation and refeeding on serum and cerebrospinal fluid concentration and on hepatic mRNA level. AB - To gain some insight into the nutritional factors that affect the blood level of transthyretin (TTR) and its metabolism, we have investigated the response of rat TTR to 1, 2 and 3 d of fasting and to 24 h of fasting followed by refeeding. The observed changes were compared to the level of TTR in cerebrospinal fluid (CSF) and to the amount of circulating thyroid hormones. Dot hybridization of a hepatic mRNA-cDNA probe specific for TTR was used to measure the relative level of TTR mRNA. Serum TTR decreased significantly after fasting and the decrease was proportional to the duration of the treatment. When rats were fasted for 24 h and then refed, serum TTR levels remained low after 2 d of refeeding. The dot hybridization results suggested that reduced liver synthesis was not the only mechanism that could explain this long-lasting effect of fasting. The TTR level in CSF was not influenced by fasting. In addition to the high sensitivity of serum TTR to food deprivation, the study also showed two distinct influences of fasting on the thyroid hormones: a primary effect that probably results in an inhibition of the conversion of thyroxine (T4) to triiodothyronine (T3) and a decreased T4-bound fraction, probably as a result of decreased serum level of TTR. PMID- 3339480 TI - Selenium and cancer prevention. PMID- 3339479 TI - Metallothionein gene expression in rats: tissue-specific regulation by dietary copper and zinc. AB - Regulation of metallothionein gene expression by dietary zinc and copper was examined in rat liver, kidney, intestine and brain using a 3 X 3 factorial design. Purified diets containing 5, 30 and 180 mg Zn/kg and 1, 6 and 36 mg Cu/kg were fed for 2 wk. Serum concentrations of copper and zinc were lower at the lowest intakes of either metal than at normal or supplemental levels. Kidney metallothionein levels were proportional to dietary zinc, being 50% less in the 5 mg Zn/kg group than in those fed the highest zinc intake. Metallothionein mRNA was measured by dot blot hybridization to a 32P-labeled oligonucleotide DNA probe representing the terminal 5' sequence of the metallothionein gene. In kidney the number of metallothionein mRNA molecules per cell increased four- to five-fold (from 4 to 29 molecules per cell) with increasing dietary zinc. A less pronounced effect on metallothionein mRNA was observed in response to dietary copper. At the lowest copper intake level and highest intake of zinc intestinal metallothionein mRNA was sevenfold greater than in any other group. Liver and brain did not respond appreciably to the dietary levels of copper and zinc that were fed. Chromatography showed that copper and zinc content of renal metallothionein was directly related to the dietary levels fed. In kidney, both metallothionein-1 and -2 genes were expressed. PMID- 3339481 TI - Epidemiological studies in nutrition: utility and limitations. PMID- 3339483 TI - How useful are routine chest x-rays of preoperative patients at risk for postoperative chest disease? AB - The authors studied the value of routine chest x-rays in the management of patients admitted for vascular surgery, a population likely to have comorbid chest disease. Patient records from 341 admissions were reviewed to determine the relationship between chest x-ray results and postoperative chest complications. Patients who had major abnormalities had a 40% postoperative complication rate, compared with 9% for those with normal x-rays; but only 13% of the complications occurred in patients with major abnormalities. Nine patients had x-ray findings that led to clinical action: three with potentially beneficial management changes (congestive heart failure in 2, fibrosis in 1) and six with potentially detrimental clinical action (false diagnosis of tuberculosis in 2, false diagnosis of nodules in 2, falsely normal chest x-ray in 2). None of 50 surgical cancellations occurred as a result of an abnormal x-ray. All the beneficial effects attributable to preoperative chest x-rays accrued to patients who had clinical evidence of chest disease. The authors conclude that routine chest x rays were not helpful in improving patient outcomes. They recommend ordering preoperative chest x-rays based on clinical indications so that the likelihood of false positives and false negatives and their associated detrimental effects can be minimized. PMID- 3339482 TI - The Diabetes Education Study: a controlled trial of the effects of intensive instruction of internal medicine residents on the management of diabetes mellitus. AB - The Diabetes Education Study was a controlled trial of the effects of physician and patient education. This article describes an educational program for internal medicine residents and its effects on ambulatory diabetes management practices. Forty-five of 86 residents practicing in the general medicine clinic of a university-affiliated city/county hospital were assigned randomly to receive a multifaceted program intended to 1) provide specific care recommendations, 2) teach necessary skills, and 3) make the professional and institutional environment more supportive. During the subsequent 11 months, 323 diabetic patients were interviewed and their records audited for evidence of changes in care. Experimental residents utilized fasting blood glucose determinations more often than controls (i.e., during 40% of visits vs. 31%, p = 0.004). Experimental residents also engaged more frequently in a variety of recommended dietary management recommendations. Isolated differences in monitoring/management of chronic complications also were found (e.g., lipid screening: 70% of experimental residents' patients vs. 58%, p = 0.016). Intensive, multifaceted programs of this nature are concluded to result in improvements in diabetes care, over and above that which is attainable through routine methods of clinical training for residents. PMID- 3339485 TI - Employment choices in conditions of physician oversupply: a study of graduates of San Francisco internal medicine programs, 1979-1984. AB - The authors surveyed 297 internists who completed residency or fellowship training at six San Francisco institutions from 1979 through 1984 to assess how the recent expanded supply of physicians has affected their intensity of practice and their decisions about location of practice. The vast majority of internists (93%) settled in metropolitan areas, with 56% remaining in the San Francisco Bay Area, despite that region's already high concentration of physicians. Mean annual income, in 1984 dollars, was slightly more than figures from national surveys of physicians of similar age ($72,560 vs. $71,900), but reported mean work week was shorter (54.8 hours vs. 60.5). Although subspecialists earned significantly more than generalists, this was because they worked more hours. Those who graduated later were significantly less likely to be in private practice in 1985, mainly because they initially selected salaried institutional work more often than earlier graduates (p less than 0.001). Women worked 85% of the men's work week and subspecialized significantly less often (p less than 0.05). These findings suggest that internists trained in already "over-doctored" areas will continue to settle there or in similar communities. PMID- 3339484 TI - Patients with acute chest pain who leave emergency departments against medical advice: prevalence, clinical characteristics, and natural history. AB - The study group identified 107 patients who left against advice from the emergency departments of three university and four community hospitals after presenting for evaluation of acute chest pain. In comparison with other emergency department patients with acute chest pain, patients who left against advice had findings that suggested they were at higher risk for myocardial infarction than patients for whom admission was not recommended but at lower risk than patients who consented to be admitted. Specific follow-up plans were made at the time of evaluation for 45 patients (42%). Survival data were obtained at 48-72 hours for 104 patients (97%) and at one month for 101 patients (94%). Fourteen patients (12%) were hospitalized within three days of their original emergency department visits, and three patients had documented acute myocardial infarctions. The only death within one month was that of a patient who died suddenly out-of-hospital later on the day of his emergency department visit. The authors conclude that patients who left against medical advice had presentations and prognoses that were in between those of patients for whom admission was not recommended and those of patients who consented to be admitted. PMID- 3339487 TI - Career development among residents completing primary care and traditional residencies in medicine at the Boston City Hospital, 1974-1983. AB - A primary care (PC) pathway was initiated within the medical residency program at Boston City Hospital (BCH) in 1974. The authors studied the PC and traditional (TD) track graduates of the program to compare career development, goals, and practice patterns. The 185 graduates of the nine resident cohorts from 1974 through 1983 were surveyed; the overall response rate was 74%. Primary care careers have been chosen by 81% of PC graduates, compared with 38% of TD graduates (p less than 0.001); career satisfaction is equally high in the two groups. Among the PC graduates, 68% are practicing in high-need areas, compared with only 37% of TD graduates (p less than 0.001). PC graduates are more likely to make house calls, provide extended office hours, round in nursing homes or chronic care facilities, and co-practice with nurse practitioners or physician's assistants, and they are more active in women's health care, care of the terminally ill, and treating patients with sexual dysfunction (all p less than 0.05). PC graduates utilize various community agencies more frequently and supplement patient education with outside resources more intensively (p less than 0.001). The career choices and practice locations of PC graduates reflect the training goals of the PC curriculum and differ from the career choices and practices of the TD graduates from the same program. PMID- 3339486 TI - Teaching the medical interview: an intervention study. AB - To study the effects of teaching specific interviewing techniques on verbal behaviors and on health outcomes, internal medicine residents working in a screening clinic were assigned to either an experimental or a control group. The entire clinic visit was audiotaped, transcribed, and coded according to the Verbal Response Mode (VRM) system. Residents in the experimental group were taught interviewing behaviors (patient exposition and physician explanation) that had been found in previous studies to be associated with patient outcomes. Through telephone interviews, patient satisfaction, compliance, and symptom status were determined for all patients. Two hundred and sixty-eight interviews (156 in the experimental group and 112 in the control group) were included in the study. Training did increase patient exposition and physician explanation, but did not affect health outcomes. Residents' attitudes and behaviors during the training are described. PMID- 3339488 TI - Changing one's mind: when is Odysseus to be believed? PMID- 3339489 TI - Early experience with peer review organizations. PMID- 3339490 TI - Can a professional society do (or sponsor) research? PMID- 3339492 TI - The melting pot: examine before stirring. PMID- 3339491 TI - Consent in medical decision making: the role of communication. AB - Informed participation in medical decisions is important because it demonstrates respect for the ethical principle of individual autonomy and increases the likelihood of reaching therapeutic goals. Twenty hospitalized patients were randomly selected and observed for six and a half hours to assess the degree to which informed participation was possible with diagnostic and therapeutic procedures. Resident physicians and patients were then interviewed about the rationale, benefit, risk, and alternative for each observed procedure. Commonly observed activities were injecting and giving oral medications, and performing invasive diagnostic procedures. Clinicians' communication involved rationale (43%) more often than benefits (34%), risks (14%), and alternatives (12%). Communication was similar when the procedures proposed were important and risky. Residents' and patients' interviews demonstrated limited congruence in shared understanding of rationale (57%), benefit (45%), risk (19%), and alternatives (25%). These results suggest that clinicians selectively impart information essential for informed patient participation, and highlight areas of clinician patient communication in need of attention. PMID- 3339493 TI - Information and authenticity: rethinking free and informed consent. PMID- 3339494 TI - Physician supply and employment choices. PMID- 3339495 TI - Influenza immunization of health care providers. PMID- 3339496 TI - (Self-) palpation orchitis. PMID- 3339497 TI - Patient understanding of implications of medical choices. PMID- 3339498 TI - Oklahoma State Department of Health. AIDS Task Force recommendations to date. March 3, 1987. PMID- 3339499 TI - Does breast feeding help protect against atopic disease? Biology, methodology, and a golden jubilee of controversy. AB - To help shed some light on the 50-year-old controversy concerning the possible protective effect of breast feeding on subsequent atopic disease, I developed 12 standards pertaining to both biologic and methodologic aspects of exposure (infant feeding), outcome (atopic conditions), and statistical analysis for studies of atopic eczema, asthma, allergic rhinitis, cow milk allergy, and other food allergy. Among the published studies on atopic eczema, the nine claiming a protective benefit of breast feeding performed less well than the 12 not making such a claim on "methodologic" standards relating to strict diagnostic criteria and blind ascertainment of outcome. The positive studies were somewhat stronger, however, on the "biologic" standards bearing on sufficient duration and exclusivity of breast feeding and on separate analysis of children at high risk. For the other atopic conditions, there were no important differences between positive and negative studies. In few negative or positive studies was there adequate control for confounding variables or examination of potential benefits relating to the severity or age at onset of atopic disease. To avoid another 50 years of unresolved controversy, future studies should improve both the biologic and methodologic aspects of their design and analysis. PMID- 3339500 TI - Effect of continued oral feeding on clinical and nutritional outcomes of acute diarrhea in children. AB - One hundred twenty-eight nonmalnourished male patients between 3 and 36 months of age were randomly assigned to receive one of four lactose-free dietary treatments to determine the effect of dietary therapy on the severity and nutritional outcome of diarrheal illness. Group 1 received a formula diet composed of casein, sucrose, dextrin with maltose (Dextri-Maltose), and vegetable oil to provide 110 kcal/kg body weight/d (CSO-110). Group 2 received CSO to provide 55 kcal/kg/d (CSO-55) for 2 days and then CSO-110. Group 3 received only oral glucose electrolyte solution (GES) for 2 days, CSO-55 for the next 2 days, and then CSO 110. Group 4 received the same diets as Group 3 except that only intravenous GES was used for the first 2 days. The GES maintenance solutions provided 24 to 30 kcal/kg/d. Therapeutic success rates were similar among dietary groups, ranging from 90% to 97%. Fecal excretion was initially lower in group 4 (P less than 0.05) but was similar initially among groups treated orally and among all four groups beginning on day 3. Net apparent absorption of nitrogen, fat, carbohydrate, and total energy; retention of nitrogen; and increments in body weight, arm circumference, and skin-fold thickness were positively related to the amounts of dietary energy consumed. Thus continued oral feeding with the CSO diets during the early phase of therapy yielded improved nutritional results. PMID- 3339501 TI - Pediatric Symptom Checklist: screening school-age children for psychosocial dysfunction. AB - The Pediatric Symptom Checklist (PSC) is a 35-item screening questionnaire that is completed by parents and designed to help pediatricians in outpatient practice identify school-age children with difficulties in psychosocial functioning. The current study assessed the validity of the PSC by screening 300 children in two pediatric practices, a middle-class group practice and an urban health maintenance organization. Validity was established by comparing the results of PSC screening of 48 children with in-depth interview assessments and pediatricians' ratings. Results indicate that the PSC has a specificity of 0.68 and a sensitivity of 0.95. The screening process was well accepted by parents and pediatricians. Several children whose pediatricians' ratings had indicated adequate functioning were identified by the PSC as having substantial psychosocial dysfunction and requiring further evaluation. PMID- 3339502 TI - Release of leukotriene C4 in respiratory tract during acute viral infection. AB - Groups of children with wheezing during respiratory illness, children without wheezing during respiratory illness, and appropriately matched healthy children were tested for the presence and concentration of leukotriene C4 (LTC4) in nasopharyngeal secretions, employing the techniques of reverse-phase high pressure liquid chromatography and radioimmunoassay. Although most wheezing children had LTC4 in nasopharyngeal secretions, the concentration of LTC4 among wheezing children who shed respiratory viruses was found to be consistently elevated (mean 1520 +/- 228 pg/0.1 mL) compared with values in wheezing children without evidence of viral infection (mean 709 +/- 147 pg/0.1 mL). In sharp contrast, little or no LTC4 activity was detected in healthy children (mean 106 +/- 77 pg/0.1 mL). These observations suggest that respiratory viruses are stimuli for the release of mediators of inflammation such as LTC4. Thus development of virus-induced bronchospasm may be related in part to direct mucosal cell-virus interaction and the release of pharmacologically active mediators in the respiratory tract. PMID- 3339503 TI - Normal aerobic and anaerobic exercise data for North American school-age children. AB - The purpose of this study was to establish normative data for untrained, healthy North American children by means of the James protocol for bicycle ergometry. Data were obtained on 151 of 185 children (70 girls and 81 boys). Their ages ranged from 7 years 6 months to 12 years 9 months. All subjects were divided into groups by gender and body surface area (BSA). Maximum heart rates were greater in girls. The mean difference between maximum and recovery heart rates differed significantly by gender, girls taking longer to recover than boys. Maximum oxygen consumption (measured in cubic centimeters per minute per kilogram body weight) did not differ in boys and girls. Ventilatory anaerobic threshold (VAT) occurred when there was an isolated increase in the slope for ventilatory equivalent for oxygen consumption (VE/VO2) with no change in the slope for ventilatory equivalent for carbon dioxide production (VE/VCO2) when both were plotted against time. Absolute oxygen consumption (VO2) at VAT increased with BSA in both sexes, and, when normalized to body size and expressed as a percent of VO2 maximum, no significant difference was observed between the sexes. These data may be used in the fitness evaluations of preadolescent children from North America. PMID- 3339504 TI - Refeeding during recovery from acute diarrhea. PMID- 3339505 TI - Congenital concomitants of infantile hypothyroidism. New England Congenital Hypothyroidism Collaborative. PMID- 3339506 TI - Newborn hospitalization: a closer look. AB - To assess the safety of moderately early hospital discharge for normal newborn infants (mean +/- SD, 31 +/- 5 hours after delivery), we compared the incidence of hospital readmission within 6 weeks of birth with the incidence of readmission among a similar cohort of infants with extended hospitalization (mean +/- SD, 92 +/- 44 hours) as a result of maternal illness. The hospital charts for all infants admitted to the well-baby nursery between January 1 and December 31, 1985, were reviewed. Fifty-two (3.0%) of the 1714 infants who were discharged moderately early and 17 (2.7%) of the 622 infants who had an extended hospitalization were readmitted to the hospital by age 6 weeks (P = NS). Maternal age, financial status, and race each failed to predict infant readmission. Only four of the 52 readmission diagnoses among infants discharged moderately early could potentially have been identified (not prevented) before discharge with an extended newborn hospitalization. These data indicate that moderately early neonatal hospital discharge does not result in an increased incidence of rehospitalization within the first 6 weeks of life. PMID- 3339507 TI - Zinc balance in premature infants given the minimal dietary zinc requirement. AB - A zinc balance study was conducted on low birth weight infants (670 to 2420 g) fed unsupplemented human milk (the mother's or pooled) (group 1, n = 17) or human milk with zinc supplementation (group 2, n = 17). The mean zinc concentrations of the diets in groups 1 and 2 were 2.2 +/- 1.1 mg/L and 8.4 +/- 0.8 mg/L, respectively, and the mean copper concentration of the diets in both groups was 0.45 +/- 0.12 mg/L. The studies were performed 7 to 128 days after birth, which corresponded to 29 to 43 weeks postconceptional age. The turning point of zinc balance from negative to positive appeared to be greatly influenced by the postconceptional age, being approximately 36 weeks in both group 1 and group 2, rather than other factors such as the zinc intake and the postnatal age. The calculated minimal requirement of dietary zinc during the period from 36 to 40 weeks postconceptional age, for an adequate amount of zinc retention in infants (250 micrograms/kg/d), was 0.8 mg/kg/d. Zinc supplementation did not appear to interfere with copper retention. PMID- 3339508 TI - Blood pressure in very low birth weight infants in the first 70 days of life. PMID- 3339509 TI - Disposition of an immunoglobulin intravenous preparation in very low birth weight neonates. AB - To assess the disposition, tolerance, and toxicity of an intravenous preparation of immunoglobulin (IGIV) in very low birth weight (VLBW) neonates, we administered single doses of 500 or 750 mg/kg to 20 neonates with birth weights between 750 and 1500 g during the first week of life. The infusion of this product was well tolerated. Modest changes in hemoglobin, hematocrit, and total hemolytic complement occurred as expected. Hepatic toxic effects were not detected. Mean peak IgG concentrations were 1564 and 1316 mg/dL for the high-dose and low-dose groups, respectively. Mean IgG concentrations were very similar for both groups on postinfusion days 1, 4, 7, 14, 21, and 28. IgG concentrations remained above 300 mg/dL in seven of 10 infants in each group by day 21, and in six of the high-dose group and seven of the low-dose group by day 28. Mean elimination half-lives were 22.6 and 22.8 days in the high-dose and low-dose groups, respectively. These data provide a basis for assessment of potential efficacy of IGIV in the prevention of late-onset infection in VLBW neonates. PMID- 3339510 TI - Effect of cephalosporins on bilirubin-albumin binding. AB - The effect of parenterally administered cephalosporins on bilirubin-albumin binding was measured in vitro by means of the peroxidase method with human serum albumin and by means of a dialysis rate method with newborn infants' serum. Ceftriaxone and cefoperazone have been shown to affect bilirubin-albumin binding. In this study, 13 additional cephalosporins were tested. Cefonicid, cefotetan, and cefmetazole competed with bilirubin for albumin binding and, at reported mean peak serum levels, decreased the reserve albumin concentration by 75%, 56%, and 40%, respectively. We suggest that these five cephalosporins may increase the risk of bilirubin encephalopathy in jaundiced neonates. PMID- 3339511 TI - Prolonged organophosphate toxicity in a twenty-six-month-old child. PMID- 3339512 TI - Fever of unknown origin, weight loss, and hepatomegaly in a 3-year-old boy. PMID- 3339513 TI - Preliminary report from a conference entitled "Prevention of adult atherosclerosis during childhood". PMID- 3339514 TI - Vitamin E status in cholestasis. PMID- 3339515 TI - Screening for drug use in adolescents: the other side of the coin. PMID- 3339516 TI - Moral and legal issues in screening for drug use in adolescents: a reply. PMID- 3339517 TI - Screening for adolescent substance use. PMID- 3339518 TI - Anagyrine-induced congenital defects. PMID- 3339519 TI - Transient central sexual precocity in a girl. PMID- 3339520 TI - Administration of vitamin A to preterm infants. PMID- 3339522 TI - Immunization of HIV-infected children. PMID- 3339521 TI - Hypernatremia after the use of an activated charcoal-sorbitol suspension. PMID- 3339523 TI - Vancomycin reactions in preterm infants. PMID- 3339525 TI - When children face death in a family. PMID- 3339524 TI - Promoting emotional health role of the nurse practitioner. PMID- 3339526 TI - Parental adaptation to cystic fibrosis. PMID- 3339527 TI - Adolescent dysmenorrhea. PMID- 3339528 TI - The gay and lesbian teen: a case of denied adolescence. PMID- 3339529 TI - Coalitions. PMID- 3339530 TI - Children with elevated lead levels. PMID- 3339531 TI - Failure to thrive. PMID- 3339532 TI - Henoch-Schonlein purpura in childhood. PMID- 3339533 TI - Children's pain perception before and after analgesia: a study of instrument construct validity and related issues. PMID- 3339534 TI - Parents' views about having a child after a SIDS death. PMID- 3339535 TI - PKU: a nursing update. PMID- 3339536 TI - Managing the process of failure. PMID- 3339537 TI - A call to dialogue. PMID- 3339538 TI - Fear and courage. PMID- 3339539 TI - Computers and nursing care. PMID- 3339540 TI - Painless cataract surgery. PMID- 3339541 TI - In defense of the Omnifit lens. PMID- 3339542 TI - Can we afford to cut costs? PMID- 3339543 TI - A three-part system for refining intraocular lens power calculations. AB - A three-part system that determines the correct power for an intraocular lens (IOL) to achieve a desired postoperative refraction is presented. The three components are (1) data screening criteria to identify improbable axial length and keratometry measurements, (2) a new IOL calculation formula that exceeds the current accuracy of other formulas for short, medium, and long eyes, and (3) a personalized "surgeon factor" that adjusts for any consistent bias in the surgeon's results, from any source, based on a reverse solution of the new formula; the reverse solution uses the postoperative stabilized refraction, the dioptric power of the implanted IOL, and the preoperative corneal and axial length measurements to calculate the personalized surgeon factor. The improved accuracy of the new formula was proven by performing IOL power calculations on 2,000 eyes from 12 surgeons and comparing the results to seven other currently used formulas. PMID- 3339544 TI - Minimal lift-multiple rotation technique for capsular bag phacoemulsification and intraocular lens fixation. AB - A method of capsular bag phacoemulsification is outlined step-by-step. The surgical technique has proven safe and efficient and preserves the architecture of the capsular bag for hard or soft intraocular lens implantation. It represents a practical, modern method for cataract extraction and intraocular lens implantation. PMID- 3339545 TI - The relationship between indoor and outdoor Snellen visual acuity in cataract patients. AB - One hundred six cataractous eyes of 78 patients were evaluated to examine the relationship between indoor and outdoor Snellen visual acuity. While 81 of all cataractous eyes (76.4%) had Snellen visual acuities of 20/40 or better when tested indoors, only 33 eyes (31.2%) had 20/40 or better Snellen visual acuities when tested outdoors facing the sun. When tested indoors, only three eyes (2.8%) had Snellen visual acuities worse than 20/80, while 31 eyes (29.2%) had outdoor Snellen visual acuities worse than 20/80. Ten eyes (9.4%) had outdoor Snellen visual acuities worse than 20/200. Seventy-four eyes (69.8%) had outdoor visual acuities that were at least two Snellen lines worse than those measured indoors and 23 eyes (21.7%) had outdoor visual acuities that were at least five Snellen lines worse. The median difference between indoor and outdoor visual acuity was three Snellen lines. The need for increased precision in the ability to assess outdoor "real world" vision while in the ophthalmologist's examination room is discussed. Clearly, indoor Snellen visual acuity alone is insufficient to evaluate functional visual impairment in cataract patients. PMID- 3339546 TI - The relationship between cataract type and glare disability as measured by the Miller-Nadler glare tester. AB - Cataract patients were tested for glare disability using the Miller-Nadler glare tester. Predicted outdoor visual acuity was then compared with the actual outdoor visual acuity. The Miller-Nadler glare test scores predicted actual outdoor visual impairment to within one Snellen line in 46.7% of the eyes, underestimated actual outdoor visual impairment by more than one Snellen line in 31.5% of the eyes, and overestimated outdoor visual impairment by more than one Snellen line in 21.7% of the eyes. Overall, 64.1% of the eyes had outdoor vision which was more closely predicted by their glare scores than by their indoor Snellen acuity. When the cataractous eyes were divided into three categories, eyes with pure nuclear sclerosis, eyes with nuclear sclerosis and posterior subcapsular opacities, and eyes with all other cataractous combinations, predictability differences were observed. Although we found that actual outdoor visual acuities were not precisely predicted by disability glare scores in a substantial proportion of our subjects, the glare scores were considerably more predictive than indoor Snellen acuity. Further development and field testing of glare testing devices as predictors of outdoor visual impairment is necessary. PMID- 3339547 TI - Photorefractive keratectomy: a technique for laser refractive surgery. AB - The excimer laser offers entirely new corneal surgery procedures. In this paper, we describe conditions for one such procedure, photorefractive keratectomy, the direct reshaping of the cornea's central optical zone using tissue ablation with far ultraviolet radiation. We present equations for the required tissue ablation to achieve required refractive corrections. Conditions for beam uniformity are presented and a method of achieving better beam uniformity using beam integration by rotation is demonstrated. The healing of rabbit corneas after area ablation was observed. Five days after treatment, the surface quality of deep cuts was very irregular; the shallow cuts produced more regular results, as predicted by our calculations of beam characteristics. PMID- 3339548 TI - Factors contributing to corneal decompensation with the Stableflex lens. AB - A retrospective review was conducted on 38 eyes with Stableflex intraocular lenses in which the lenses were removed or the eye had penetrating keratoplasty. Preoperative axial length measurements were significantly lower in eyes with Stableflex lenses than in control eyes. Based on these data, axial length measurements may be valuable in predicting which eyes will develop corneal problems with small-diameter, closed-loop anterior chamber lenses. Axial lengths may also be beneficial in deciding preoperatively which eyes may need smaller size anterior chamber lenses of other designs. This is believed to be the first report linking short axial lengths to problems with anterior chamber lenses and recommending the use of axial length measurements for preoperative sizing of anterior chamber lenses. PMID- 3339549 TI - Cataracts in Dunedin Program participants: an evaluation of risk factors. AB - A geriatric health screening program in Dunedin, Florida, was used to evaluate risk factors leading to development of cataracts. A total of 2,787 participants completed the fourth yearly visit to the program. At the time of the fourth visit, 49.3% of women (mean age 75.1 years) and 38.2% of men (mean age 75.4 years) reported the presence of cataracts. Age was found to be the most significant risk factor in cataract development (P less than .0001). Both men and women with cataracts had significantly lower serum cholesterol concentrations than subjects without cataracts. After adjusting for age and sex, diazepam (P less than .03), furosemide (P less than .04), isosorbide (P less than .003), and ibuprofen (P less than .03) were found to be positively associated with cataracts; triamterene (P less than .05) had a negative association, indicating a protective relationship. Aspirin was not shown to have a protective effect on reported cataracts. PMID- 3339550 TI - Measuring the power of an in situ intraocular lens with the keratometer. AB - A method to measure the power of an intraocular lens (IOL) in situ using an extended range keratometer and a depth measuring apparatus is described. With this method, the IOL power was measured in ten patients with an anterior chamber IOL and in ten patients with a posterior chamber IOL and compared with the labeled power. The total mean error (measured power minus labeled power) was found to be 0.01 diopters (D) with a standard deviation of 0.22 D. The largest error was 0.40 D. PMID- 3339551 TI - Effect of a plano-convex posterior chamber lens on capsular opacification from Elschnig pearl formation. AB - Opacification of the posterior capsule occurs most commonly from Elschnig pearl migration or fibrosis. The physical contact of a posterior chamber lens, particularly one with a reverse optic, has been postulated to decrease the rate of capsular opacification by creating a barrier to Elschnig pearl migration. This randomized prospective clinical study comparing the 3M style 34S convex-plano optic and style 34R plano-convex (reverse) optic posterior chamber lens demonstrated a statistically significant reduction in capsular opacification by Elschnig pearls at one year in the reverse optic lenses (18.2% versus 7.6%, P = .03). No statistically significant difference in capsular fibrosis rates was noted (2.5% versus 4.5%, P = .48). The reverse optic implant also demonstrated greater iris to implant optic clearance. PMID- 3339552 TI - Fibrinous membrane formation on the posterior chamber lens during the early postoperative period. AB - I observed transient membrane formation consisting primarily of fibrin on the anterior surface of the IOL in 45 (7.6%) of the 596 eyes that received posterior chamber lens implantation during the past year. The onset of the condition was generally five to six days after surgery. This membrane characteristically developed between the margins of the anterior capsule, and therefore might be the result of lens-induced uveitis from the proliferation of lens epithelial cells under the anterior capsule. PMID- 3339554 TI - A controlled method of removing the Stableflex lens. AB - It has been reported that the Stableflex lens, marketed by Optical Radiation Corporation, can be difficult to remove if one is not experienced with the procedure and the special characteristics of the lens. A new method, using the lens haptics as an aid in its removal, is described. This method is relatively atraumatic if the surgeon is familiar with the tendency of Stableflex lens loops to erode deeply into ocular tissues. Careful controlled amputation of the loops is necessary before the remaining portion of the loop is gently removed from tissue encapsulation. PMID- 3339553 TI - Pharmacologic pupillary modulation in the perioperative period. AB - The perioperative management of the pupil is essential to the success of anterior segment surgery. A new dilating regimen was tested in 65 cases of cataract extraction and intraocular lens implantation. The alpha-adrenergic agonist, phenylephrine 2.5%, was used after pretreatment with the adrenergic beta-blocker, timolol 0.5%. This treatment successfully dilated the pupil in all but three cases, was maintained by intraoperative epinephrine infusion, and was readily reversed with intraocular acetylcholine. We conclude that this pharmacologic regimen provided a successful and easily reversible mydriasis during surgery. PMID- 3339555 TI - Light-induced maculopathy and cystoid macular edema. AB - We present two patients with paramacular burns induced by the operative light microscope. In one case there was associated cystoid macular edema. Of the 34 total reported cases of paramacular burns, there have been only two cases of cystoid macular edema. Thus, although the total number of reported cases of light induced maculopathy is small, this disorder does not appear to predispose to cystoid macular edema. Loss of visual acuity is mainly caused by the proximity of the burn to the fovea. PMID- 3339556 TI - Pupillary peaking with exposure of an intraocular lens positioning hole corrected by Nd:YAG laser treatment. AB - After posterior chamber intraocular lens insertion, a patient complained of "glare" and of seeing an "extra line." The pupil was seen to be "peaked" at the 10-o'clock meridian, exposing a lens positioning hole. Following dilation, adhesions between the anterior capsule remnants and the posterior iris surface were seen. These adhesions were severed with a Nd:YAG laser, restoring the normal pupillary shape and eliminating the patient's optical aberrations. PMID- 3339557 TI - Choosing an intraocular lens for patients with large pupils. AB - Optical aberration from the positioning holes of a posterior chamber intraocular lens was encountered in three patients with wide spontaneous dilation of the pupil in scotopic conditions. One patient had a cataract extraction in his fellow eye with implantation of a posterior chamber lens without positioning holes in its optical portion and has not encountered any aberrations in that eye. We suggest that in such patients, careful preoperative measurement of the pupillary size in a dark room should be done and lenses without positioning holes on the optic should be used to prevent optical aberrations. PMID- 3339558 TI - Dense cataract in only eye. PMID- 3339559 TI - Intraocular lens exchange and vitrectomy for chronic pseudophakic cystoid macular edema. PMID- 3339560 TI - Autogenous tissue glue. PMID- 3339561 TI - Meaningful evaluation of refractive surgery. PMID- 3339562 TI - Loneliness. A conceptual model. PMID- 3339563 TI - Separation in the adolescent therapeutic community. PMID- 3339564 TI - Quality assurance. AB - The QA process is recommended to anyone seeking to upgrade patient care delivery. It clarifies theories and gives substance to progressive ideas being considered for adoption. Certainly it tends to prevent premature and ill-conceived presentations. When an action is instituted, QA provides the framework that can be used to facilitate the change. As an afterthought, but as a welcome benefit, QA can foster teamwork and camaraderie among staff who assist in problem solving or bringing an idea to fruition. PMID- 3339565 TI - Addicted adolescent girls. Familial interpersonal relationships. PMID- 3339566 TI - DSM-III and homosexuality. PMID- 3339567 TI - PTSD and the family. PMID- 3339568 TI - The legacy of suicide. PMID- 3339569 TI - Tuberculosis among the central London single homeless. A four-year retrospective study. PMID- 3339571 TI - Techniques for ensuring that your next paper is quite unsuitable for publication. PMID- 3339570 TI - The changing face of geriatric medicine in North Staffordshire. PMID- 3339572 TI - Medical outpatients. PMID- 3339573 TI - Oestrous cycles and the breeding season of the Pere David's deer hind (Elaphurus davidianus). AB - Reproductive cycles were studied in a group of tame Pere David's deer hinds. The non-pregnant hind is seasonally polyoestrous and, in animals studied over 2 years, the breeding season began in early August (2 August +/- 3.3 days; s.e.m., N = 9) and ended in mid-December (18 December +/- 5.7 days; N = 8) and early January (6 January +/- 3.2 days; N = 11) in consecutive years. During the anoestrous period, plasma progesterone concentrations were low (0.2 +/- 0.01 ng/ml) or non-detectable. There was a small, transient increase in progesterone values before the onset of the first cycle of the breeding season. In daily samples taken during an oestrous cycle in which hinds were mated by a marked vasectomized stag, progesterone concentrations remained low (less than 0.5 ng/ml) for a period of about 6 days around the time of oestrus, showed a significant increase above oestrous levels by Day 4 (Day 0 = day of oestrus) and then continued to increase for 18 +/- 2.8 days to reach mean maximum luteal levels of 3.5 +/- 0.6 ng/ml. The plasma progesterone profiles from a number of animals indicated that marking of the hinds by the vasectomized stag did not occur at each ovulation during the breeding season and therefore an estimate of the cycle length could not be determined by this method. In the following year, detection of oestrus in 5 hinds was based on behavioural observations made in the absence of the stag. A total of 19 oestrous cycles with a mean length of 19.5 +/- 0.6 days was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339574 TI - A detailed analysis of early events during in-vitro fertilization of bovine follicular oocytes. AB - Bovine follicular oocytes collected at slaughter were matured and fertilized in vitro with in-vitro capacitated spermatozoa. Analysis of 621 penetrated ova fixed at various times after in-vitro insemination led to definition of 6 stages of early development. A time sequence for sperm penetration, sperm head decondensation, male pronucleus formation, the activation of second meiotic division, female chromosome decondensation and pronucleus development was established. First sperm penetration into the ooplasm was recorded 6 h after insemination; 1-2 h was required for the sperm head to decondense and another 4-6 h to develop into the opposing pronucleus stage. Synkaryosis and first cleavage occurred 28 h after fertilization. Examination of the early stages revealed four types of abnormalities, i.e. polyspermy, polygyny, asynchrony between male and female pronucleus development, and preactivation of cytokinesis. PMID- 3339576 TI - Oocyte size and intrafollicular position in polyovular follicles in rabbits. AB - Healthy follicles with 2-24 oocytes were observed in adult rabbit ovaries during all phases of folliculogenesis from primary to preovulatory follicles. Most follicles contained 2-3 oocytes which developed according to their topographical situation in the follicle. The central oocyte in a normal topographical situation has an almost normal growth and development up to metaphase II and cumulus expansion. The peripheral oocytes grow more slowly: most do not attain the normal size or resume meiosis and remain surrounded by ordinary granulosa cells. When the number of oocytes is higher than 3, the peripheral oocytes develop even more slowly, as do the central ones. It demonstrates the necessity for the oocyte to occupy a certain position inside the follicle and to reach a size which allows resumption of meiosis; the cumulus responds only to oocytes of normal size and position. We suggest that, despite the relative frequency of binovular follicles, fertilization of two oocytes originating from one follicle is unlikely. PMID- 3339577 TI - Characterization of the human zona pellucida from fertilized and unfertilized eggs. AB - Zonae pellucidae were isolated from a variety of human eggs collected from follicular aspirates for in-vitro fertilization. Zonae were removed from pools of eggs classified as fertilized but unsuitable for embryo transfer, inseminated but not fertilized, and immature and not inseminated. Isolated zonae were heat solubilized, iodinated and separated by two-dimensional electrophoresis. Under reducing conditions, zonae from unfertilized eggs separated into three acidic proteins with molecular weight ranges of 90,000-110,000 (ZP1), 64,000-78,000 (ZP2) and 57,000-73,000 (ZP3). Under non-reducing conditions, ZP1 and ZP2 co migrated at Mr 92,000-120,000. An identical pattern was seen from zonae isolated from eggs that were not inseminated. Therefore, if chemical modification of the zona is effected by spermatozoa, these changes were not apparent in the electrophoretic patterns. The electrophoretic pattern of zonae isolated from eggs classified as fertilized revealed fertilization-associated modification of the zona pellucida. This was expressed as a modification of the ZP1 molecule, and was only evident after reduction of the sample. We suggest that this modification may be effected by egg cortical granule dehiscence after fertilization and that the chemical modification of the zona may be involved in a zona block to polyspermy. PMID- 3339575 TI - Mitochondrial DNA in the mouse preimplantation embryo. AB - Total DNA was extracted from mouse embryos that were collected from CD-1 random bred females on Day 1 of pregnancy and cultured for up to 4 days in vitro, or from the reproductive tracts of pregnant females on Days 1, 3, 4 and 5 of pregnancy. Southern blot analyses with a cloned mouse mitochondrial DNA probe were performed to determine the relative levels of mitochondrial DNA in the zygote, morula, blastocyst and early egg cylinder stage embryos. The results indicated that the total amount of mitochondrial DNA does not change during development of the mouse embryo up to the egg cylinder stage and is not altered during in-vitro culture of the fertilized one-cell embryo to the blastocyst stage. PMID- 3339578 TI - Effect of endometriosis on ovulation, ovum pickup, fertilization and tubal transport in the rabbit. AB - In 25 rabbits (Group E) endometrium from the right uterine horn was transplanted onto the peritoneum. In 25 rabbits (Group C) fat was transplanted. After a recovery period of 12 weeks the does were mated, and killed 24 h later. In Group E the implants had changed into cysts of 5-15 mm in diameter. Histological examination revealed endometrial glands and stroma in every specimen. Periadenexal adhesions did not develop in any animal. No differences were found between Groups C and E in the number of corpora lutea, the recovery rate, the fertilization rate and the transport of fertilized ova. These findings indicate that endometrial implants in the rabbit have no influence on the ovulatory mechanisms, the pickup function of the oviduct, the fertilization rate or on the transport of fertilized ova. Taking into account the restrictions of a rabbit model, it is suggested that the decreased fecundity in mild endometriosis in the human may be caused by disturbances in post-fertilization events, i.e. development of the pre-implantation embryo or implantation. PMID- 3339579 TI - Cellular and biochemical characteristics of semen obtained from pubertal chimpanzees by masturbation. AB - Semen characteristics were studied in 6 wild-born chimpanzees with dental ages ranging approximately from 6 to 12 years. The animals formed 2 groups, early pubertal (EP, N = 3, 6-9 years) and late pubertal (LP, N = 3, 11-12 years). Mean body weight, testicular volume and serum androgen concentration were significantly lower in Group EP (32.2 +/- 1.6 kg, 34.0 +/- 7.7 cm3, 2.1 +/- 0.1 ng/ml) than in Group LP (55.7 +/- 5.7 kg, P less than 0.01; 100.5 +/- 11.9 cm3, P less than 0.01; 3.6 +/- 0.7 ng/ml, P less than 0.05). Ejaculates were obtained by masturbation in all subjects. The mean ejaculate volume was lower in Group EP (0.56 +/- 0.20 ml) than in Group LP (3.77 +/- 0.73 ml, P less than 0.01). In Group EP, 2 animals were azoospermic while the third produced semen with means of 57.1 x 10(6) spermatozoa per ml, 20% motility and 40% vitality. These values were low when compared with the mean values of Group LP (376 x 10(6) spermatozoa per ml, 67% motility and 78% vitality). Mean total sperm count was correlated with testicular volume (r = 0.84) and serum androgen concentration (r = 0.96). The mean concentrations of L-carnitine, fructose, citrate and acid phosphatase for the two groups were not significantly different; but, related to the differences in ejaculate volumes, their total amounts in total ejaculate were lower in Group EP than in Group LP. These results suggest that, in chimpanzees, mechanisms of seminal plasma production and ejaculation are functional early in the reproductive life and that the emission of spermatozoa occurs later. PMID- 3339580 TI - Relation between circulating sex steroid concentrations and sexual behaviour during pregnancy and post partum in the domestic rabbit. AB - Sexual behaviour of 16 female and 12 male rabbits was studied during pregnancy and early post partum. The main behavioural events of the male (nuzzling and mounting) did not differ in the presence of receptive or non-receptive females. When introduced into the cage of the male, receptive and non-receptive females flattened to the floor or circled around. Sexual receptivity to males decreased in early pregnancy and increased to a maximum a few days around parturition; on Days 1 and 6 post partum, all experimental rabbits submitted to mating. Two groups of females were distinguished: one group submitting to mating whatever the stage of pregnancy, the second being receptive only during the few days before parturition or post partum. During pregnancy and early post partum there was no relation between the colour of the vulva and the female sexual behaviour. Does remained sexually receptive even when progesterone concentrations were high. Nevertheless, the number of receptive females was higher when progesterone concentrations decreased around parturition and the mean daily progesterone values were consistently higher in non-receptive than in receptive females. Oestrogen concentrations during pregnancy were very low and were not related to receptive behaviour. PMID- 3339581 TI - Histological study of follicular atresia in the ovary of the domestic hen (Gallus domesticus). AB - Semi-serial (1 in 20) sections of ovaries were studied and only two types of atresia were identified--non-bursting and bursting. Smaller, non-yolky follicles (less than 1 mm diameter) showed non-bursting atresia. Atresia in follicles greater than 1 mm diameter was invariably of the bursting type which involved the rupture of the follicular wall, and the extrusion of yolk and cellular debris through the rupture site into the stroma. However, this rupture site was small and consequently was not visible in every section but it could always be seen when the follicle was followed in semi-serial sections. The mitotic index of granulosa cells in bursting atretic follicles was much lower than that for normal follicles. The most common criteria for distinguishing non-bursting atretic follicles were the extremely shrunken, irregularly shaped oocytes and the separation of the granulosa from the theca. In bursting atretic follicles, reliable indications were the presence in the ooplasm of some cells or cellular debris, and disorganization of the yolk and granulosa tissue. The presence of pycnotic nuclei in the granulosa cells was not a consistent feature of all atretic follicles of the hen. PMID- 3339583 TI - Urinary hormone analysis as a diagnostic tool to evaluate the ovarian function of female gorillas (Gorilla gorilla). AB - Daily urine samples were collected from 4 adult female gorillas over 7 menstrual cycles. Urinary oestrone conjugate and pregnanediol-3-glucuronide (PDG) were measured by radioimmunoassay; LH was measured by enzyme immunoassay and each hormone was indexed by creatinine. The quantity of urinary LH during the ovulatory surge was positively correlated with the quantity of PDG excreted during the luteal phase (r = 0.87, P = 0.0013). The observations indicate a relationship between the quality of the LH surge and the levels of PDG in the luteal phase and suggest that both the LH surge and subsequent luteal phase function may be predictable from the oestrogen excretion profile during the follicular phase. PMID- 3339582 TI - Time-related effects of arginine vasopressin on steroidogenesis in cultured mouse Leydig cells. AB - The dose and time treatment effects of arginine vasopressin (AVP) on basal and hCG-stimulated testosterone accumulation by purified mouse Leydig cells in primary culture were examined. Pretreatment for 24 h of Leydig cells with AVP caused a stimulation of the acute (3 h) basal testosterone accumulation. In these conditions, progesterone accumulation was also increased. The stimulatory effect of AVP (10(-11)-10(-5) M) on testosterone accumulation was dose-dependent and as little as 10(-11) M-AVP caused significant stimulation whilst maximal effect was achieved with 10(-7) M. Oxytocin (10(-6) M) also showed a stimulation of testosterone accumulation in basal conditions, but the other peptides tested at the same concentration (neurotensin, somatostatin and substance P) did not have any effect. When Leydig cells were exposed to AVP for a longer period (48 or 72 h), the increase in basal testosterone accumulation disappeared. AVP treatment of Leydig cells for 72 h led to a significant and dose-dependent reduction in the hCG-responsiveness without altering the slope of the hCG dose-response curve. This inhibitory effect, which was also observed when AVP-pretreated Leydig cells were acutely challenged for 3 h with 8-bromo-cAMP, was accompanied by a concomitant increase in progesterone accumulation. These results indicate that AVP can exert a dual effect on mouse Leydig cells: stimulatory on basal testosterone accumulation during short-term exposure (24 h) and inhibitory on the response to hCG stimulation after long-term treatment (72 h). They provide additional evidence that neurohypophysial peptides directly affect Leydig cell steroidogenesis. PMID- 3339584 TI - Factors affecting the cryosurvival of mouse two-cell embryos. AB - A series of 4 experiments was conducted to examine factors affecting the survival of frozen-thawed 2-cell mouse embryos. Rapid addition of 1.5 M-DMSO (20 min equilibration at 25 degrees C) and immediate, rapid removal using 0.5 M-sucrose did not alter the frequency (mean +/- s.e.m.) of blastocyst development in vitro when compared to untreated controls (90.5 +/- 2.7% vs 95.3 +/- 2.8%). There was an interaction between the temperature at which slow cooling was terminated and thawing rate. Termination of slow cooling (-0.3 degrees C/min) at -40 degrees C with subsequent rapid thawing (approximately 1500 degrees C/min) resulted in a lower frequency of blastocyst development than did termination of slow cooling at -80 degrees C with subsequent slow thawing (+8 degrees C/min) (36.8 +/- 5.6% vs 63.9 +/- 5.7%). When slow cooling was terminated between -40 and -60 degrees C, higher survival rates were achieved with rapid thawing. When slow cooling was terminated below -60 degrees C, higher survival rates were obtained with slow thawing rates. In these comparisons absolute survival rates were highest among embryos cooled below -60 degrees C and thawed slowly. However, when slow cooling was terminated at -32 degrees C, with subsequent rapid warming, survival rates were not different from those obtained when embryos were cooled to -80 degrees C and thawed slowly (52.4 +/- 9.5%, 59.5 +/- 8.6%). These results suggest that optimal cryosurvival rates may be obtained from 2-cell mouse embryos by a rapid or slow thawing procedure, as has been found for mouse preimplantation embryos at later stages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339585 TI - Influence of melatonin on the testicular regression induced by subcutaneous testosterone pellets in male rats kept in long or short photoperiod. AB - Daily afternoon injections of 25 micrograms melatonin for 12 weeks had no effect on testicular weights of male rats kept in long photoperiod (14L:10D); similarly, exposure of rats to short photoperiod (2L:22D) had no effect on gonadal weight. However, rats maintained in a long or short photoperiod and implanted every 2 weeks with a 15 mm Silastic pellet containing testosterone showed a significant reduction in testicular weight; this effect was more pronounced in rats exposed to a short photoperiod. Melatonin injections in testosterone-treated rats in a long photoperiod exacerbated the inhibitory effects of testosterone alone. Subcutaneous 2-weekly implants of a beeswax pellet containing 1 mg melatonin reversed the effects of the melatonin injections on relative testicular weights but not those due to short photoperiod exposure. Testosterone implants significantly reduced pituitary LH values in long and short photoperiod-exposed animals, more particularly in those exposed to short photoperiod. Melatonin injections alone or in combination with melatonin pellets did not further exaggerate the depression in pituitary LH due to testosterone alone in long photoperiod-exposed animals; similarly melatonin pellets did not reverse the depression in pituitary LH observed. No significant differences in plasma prolactin concentrations or in thyroxine concentrations or free thyroxine index were observed after any combination of treatments. We therefore suggest that the effects observed with short photoperiod may be due to melatonin. PMID- 3339586 TI - Thermoregulation in the female hedgehog, Erinaceus europaeus, during the breeding season. AB - The body temperatures of 3 breeding and 7 non-breeding female hedgehogs were monitored during 3 years. Lactating females had significantly higher and less variable body temperatures than did pregnant and non-breeding hedgehogs. Breeding females had circadian body temperature cycles that were more biphasic than those of non-breeders. Females maintaining higher mean daily body temperatures showed less variability about the mean than those exhibiting lower mean daily body temperatures. The rate at which body temperatures became more variable as mean daily body temperatures fell was 4.6 times more rapid in non-breeding females than in pregnant and lactating hedgehogs. With the exception of a single female in late gestation, hedgehogs readily became torpid under conditions of low ambient temperature and short photoperiod during summer, particularly when their food intake was restricted. PMID- 3339587 TI - Changes in endometrial vascular permeability during the periimplantation period in the ferret (Mustela putorius). AB - A highly localized increase in permeability of uterine blood vessels in the immediate vicinity of implanting blastocysts was first detected on the morning of the 12th day of pregnancy (290 h post coitum). The amount of extravasated dye which accumulated at implantation sites continued to increase through the evening of Day 13 (321 h p.c.). Blastocyst expansion, as indicated by small uterine swellings, preceded a detectable change in vascular permeability by about 10 h, suggesting that the timing of increased permeability is closely associated with initial blastocyst attachment to the uterine epithelium. The results do not support the hypothesis that prostaglandins are required for increased uterine vascular permeability as two doses of indomethacin (4 and 8 mg/kg body wt) administered 5 times/day failed to decrease endometrial vascular permeability. However, the 8 mg dose did cause a significant reduction in size and number of uterine swellings and delayed or inhibited attachment of the trophoblast to the uterine epithelium in 2 of 5 ferrets. These findings suggest that prostaglandins play an important role in the process of implantation that is unrelated to decidual formation as the ferret is an adeciduate species. PMID- 3339588 TI - Endocrine changes, with special emphasis on oestradiol-17 beta, prolactin and oxytocin, before and during labour and delivery in goats. AB - Jugular plasma concentrations of oestradiol-17 beta, prolactin, progesterone and 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) were measured at 2-h intervals during the last 4 days of pregnancy in 6 goats. During advanced labour and delivery, samples were obtained more frequently and assayed for oxytocin. The animals were housed in a barn with continuous dim lighting. A distinct pattern of oscillation in prolactin concentrations, with peaks during the late afternoon, was apparent during the last 3 days. Geometric means of peak concentrations doubled each day and became of longer duration; night-time nadir values remained low except during the last night before parturition. A progressive increase in oestradiol-17 beta, with mean levels doubling every 36 h, was apparent during the last 3 days. There was no sharp pre-partum increase in oestradiol-17 beta. Correlated (r = 0.83) with the increase in oestradiol-17 beta was a gradual increase in PGFM and when the latter reached approximately 1000 pg/ml, the non reversible decline in progesterone reflecting pre-partum luteolysis occurred. Subsequent changes in PGFM related closely to an approximately 20-fold increase in the ratio of oestradiol-17 beta to progesterone until maximal PGFM levels of 26.5 +/- 4.2 ng/ml were reached at delivery. Basal concentrations of oxytocin (8 15 microU/ml) were measured before the last 60 min and markedly higher, though erratic, concentrations were detected at various times before appearance of the allantochorion. Maximal oxytocin values (range 180-1570 microU/ml) occurred within minutes before or after delivery of the first fetus. The results suggest that increased pre-partum production of oestradiol-17 beta, in addition to provoking sufficient release of prostaglandins to cause luteolysis, may modulate either the sensitivity or set-points for an endogenous rhythm in prolactin secretion at the end of pregnancy. The nature of the oxytocin changes suggest that, after labour has evolved sufficiently, delivery is precipitated by an abrupt increase in oxytocin secretion. PMID- 3339589 TI - Inhibitory effects of (S)-3-chlorolactaldehyde on the metabolic activity of boar spermatozoa in vitro. AB - (S)-alpha-Chlorohydrin and 3-chloro-1-hydroxyacetone inhibited the oxidative metabolism of fructose by boar spermatozoa only after a period of incubation in which they presumably underwent conversion to (S)-3-chlorolactaldehyde, an inhibitor of sperm glyceraldehyde 3-phosphate dehydrogenase. With glycerol as substrate, 3-chloro-1-hydroxyacetone had a similar effect, (S)-alpha-chlorohydrin was ineffective while (R,S)-3-chlorolactaldehyde was immediately effective with either substrate. All three compounds caused the accumulation of fructose 1,6 bisphosphate and dihydroxyacetone phosphate from fructose but not from glycerol which led to the conclusion that inhibition of triosephosphate isomerase was also associated with the anti-glycolytic action of (S)-3-chlorolactaldehyde. (S)-3 Chlorolactaldehyde caused the depletion of ATP in incubates of boar spermatozoa metabolizing fructose but not glycerol. This suggests that futile substrate cycling may play an important function in the anti-glycolytic action of (S)-3 chlorolactaldehyde and/or that boar spermatozoa can synthesize ATP from glycerol by a mechanism not involving the glycolytic pathway. PMID- 3339590 TI - Ram-specific effects on in-vitro fertilization and cleavage of sheep oocytes matured in vitro. AB - The present experiments were designed to identify possible male-specific effects on early embryonic development in vitro: Sheep oocytes were matured in vitro for 24-26 h and then fertilized in vitro using equal numbers of viable spermatozoa from 1 of 6 Clun Forest rams. At 15-18 h after insemination, oocytes were either fixed and examined for fertilization and polyspermy or further cultured in modified M 199 medium for 3 days in an oviduct epithelial co-culture system. There were significant differences in 5 separate trials between the rams with respect to the rate of fertilization, degree of polyspermy and cleavage rate after monospermic fertilization. The mean rate of fertilization varied from 89% in Ram B to 43% in Ram C while the percentage of polyspermic eggs varied from 5 to 34%. Both the absolute number of embryos cleaving to the 16-cell stage and the calculated percentage of monospermic eggs reaching the 16-cell stage differed markedly between groups of eggs fertilized by different rams. The results indicate that the development of sheep eggs in vitro is differentially affected by the ram from which the spermatozoa are collected. PMID- 3339591 TI - Changes in LH pulse frequency and serum progesterone concentrations during the transition to breeding season in ewes. AB - To characterize the changes in LH pulse frequency during the transition to breeding season. LH pulse patterns and serum progesterone profiles were determined in 8 intact ewes from mid-anoestrus to the early breeding season. Overall, 8 increases in LH pulse frequency were observed and these were restricted to 5 ewes. Of the 8 increases, 7 occurred during the 4 weeks before the first cycle, 5 of them within 1 week after a pulse frequency typical of anoestrus (0-2 per 8 h). Six of them occurred less than 1 week before either a full-length luteal phase (n = 2) or a 1-3-day increment in progesterone (n = 4). Seven of these brief progesterone increases were observed in 6 ewes, 5 of them immediately preceding the first full-length luteal phase. These results are consistent with the hypothesis that the seasonal decrease in response to oestradiol negative feedback at the beginning of the breeding season causes an increase in GnRH, and thereby LH pulse frequency. In addition, they demonstrate that the first increase in tonic LH secretion occurs in less than 1 week and, in most ewes, initiates either the first full-length cycle or a transient increase in progesterone, the latter occurring more often. PMID- 3339592 TI - An antiserum against protamines for immunohistochemical studies of histone to protamine transition during human spermiogenesis. AB - Specific polyclonal antisera have been obtained against total human protamines isolated from purified sperm nuclei. The specificity of antibodies was assessed in immunodotting and immunoblotting assays. In this preliminary report, these specific antibodies were used as probes for in-situ determination of histone to protamine transition during human spermiogenesis. Protamine-containing sites were detected on sections of human testes by light microscopy using the immunoperoxidase technique. As in other mammals, protamines appear and concentrate in condensed nuclei of elongating spermatids, i.e. during the later steps of human spermiogenesis. PMID- 3339593 TI - Sexing of preimplantation mouse embryos by measurement of X-linked gene dosage in a single blastomere. AB - Single blastomeres were isolated from zona-free 8-cell mouse embryos and assayed for X-linked hypoxanthine phosphoribosyl transferase (HPRT) activity and autosome linked adenine phosphoribosyl transferase (APRT) activity. At this stage of development both X chromosomes are active in female embryos. Hence, a bimodal distribution of HPRT: APRT ratios, corresponding to male (XY) and female (XX) biopsied samples, was observed due to the 2-fold difference in gene dosage for HPRT activity. Batches of putative male and female embryos identified in this way were transferred to pseudopregnant recipient females. Development of the seven eighths embryos was equivalent to that of control zona-free intact embryos. Sex determination by measurement of X-linked gene dosage was accurate and rapid enough to allow transfer of embryos of known sex without the need for cryopreservation. PMID- 3339594 TI - Chromosome pairing and germ cell loss in male and female mice carrying a reciprocal translocation. AB - Female carriers of the T(5;12)31H reciprocal translocation had an average reduction of 73% in oocyte numbers compared with normal litter mates, which was of a magnitude similar to the reduction in sperm counts of male carriers. Analysis of synaptonemal complexes showed that the translocated chromosomes appeared as quadrivalents, or trivalents and univalents, or bivalents in both sexes. Quadrivalents were of three types: fully synapsed, with asynapsis confined to breakpoints, and with unsynapsed ends. There was more pairing in spermatocytes than in oocytes: 37% of spermatocytes, but only 14% of oocytes, contained a fully synapsed quadrivalent, and trivalents were also more frequently fully synapsed in spermatocytes. When these results are compared with those previously obtained for other chromosome anomalies, it becomes evident that there are considerable differences in chromosome pairing between males and females, and that different chromosome rearrangements differ in the relative amount of pairing failure occurring in male and female carriers. PMID- 3339595 TI - Fetal development, and placental and maternal plasma concentrations of progesterone in the little brown bat (Myotis lucifugus). AB - Progesterone concentrations measured in plasma samples from 280 bats captured during pregnancy or early lactation were related to fetal attributes indicative of stage of pregnancy. Fetal weight increased exponentially from 40 mg at crown rump length of 6 mm to 2000 mg at 23 mm (term). Fetal weights at term accounted for up to 35% of the weight of intact pregnant animals. Progesterone concentrations increased from less than 5 ng/ml at 2 mm estimated crown-rump length to plateau values of approximately 65 ng/ml (geometric means) from 16 mm crown-rump length until the most advanced stages of pregnancy. Mean concentration in 8 post-partum bats, most of which were actively lactating, was 8.4 ng/ml; 11.6 ng/ml was measured in one animal that was carrying a wet neonate when sampled yet was still pregnant when captured 5 h earlier. Placental concentrations of progesterone ranged from 43 to 964 ng/g wet weight of tissue and mean values increased in a similar fashion though were about 4-fold greater than changes in plasma concentrations of the steroid. The concentrations in placental tissue were at least 15- to 20-fold higher than could be expected from blood contamination, indicating that placental steroidogenesis is likely to occur in this species. PMID- 3339597 TI - An in-vivo model to examine the electromyographic activity of isolated myometrial tissue from pregnant sheep. AB - Strips (2.5 x 3.5 cm) of myometrium alone (MYO) or endometrium/myometrium (ENDO/MYO) were removed from the pregnant horn of sheep (Day 110 of gestation) and transplanted to sites within the omental fat. These explants developed regular bursts of electromyographic (EMG) activity over a period of 7-10 days, as well as a dose-dependent stimulatory response to oxytocin (50-200 mU i.v.). The frequency (per 2 h) of EMG bursts in the MYO (5.3 +/- 0.2) and ENDO/MYO (5.2 +/- 0.3) explants was significantly greater (P less than 0.05) than that of the uterine myometrium (3.0 +/- 0.1), while burst duration (min) in MYO (4.1 +/- 0.2) and ENDO/MYO (4.1 +/- 0.2) explants was significantly (P less than 0.05) less than in the uterine myometrium (7.3 +/- 0.1). The EMG bursts were asynchronous between the explants and uterus, although systemic administration of oxytocin produced a synchronous burst of EMG activity in all three tissues. No differences in EMG activity or responsiveness were apparent between MYO and ENDO/MYO explants. Histological examination of the explant tissue revealed the presence of smooth muscle fibres regularly orientated into two layers; some loss of endometrial tissue was apparent in ENDO/MYO explants. To validate the mechanical integrity of this model we examined the in-vitro contractile activity of myometrial strips prepared from the explants. The strips developed regular spontaneous contractions and demonstrated a dose-dependent stimulation in response to the addition of oxytocin (10(-10) to 10(-4) M) to the bath fluid. These results suggest that spontaneous contractures during pregnancy are probably not due to pulsatile release of stimulants into the systemic circulation, or the direct diffusion of stimulants from intrauterine tissues to the myometrium but are probably caused by factors within the myometrium itself. PMID- 3339596 TI - Serum concentrations of oestradiol and progesterone, and sexual behaviour during the normal oestrous cycle in the leopard (Panthera pardus). AB - Three mature nulliparous female leopards were studied for 5 years. During three separate 6-month periods serum oestradiol and progesterone concentrations were measured at weekly intervals. Oestradiol was elevated over 21 pg/ml for 54 weeks during these 3 periods, and 36 oestradiol peaks (65.8 +/- 6.3 pg/ml (mean +/- s.e.m.), range 21-172 pg/ml) were identified. Daily frequency of feline reproductive behaviours averaged over each week increased from 1.9 +/- 0.2 (n = 93) during weeks with low serum oestradiol concentrations (less than 21 pg/ml) to 5.3 +/- 0.6 (n = 54) during weeks when serum oestradiol concentrations (greater than 21 pg/ml) were high. Increased serum progesterone concentrations (13-98 n/gml) were observed on 5 occasions in 2 leopards housed together. These presumptive luteal phases lasted from 1 to 5 weeks. Baseline progesterone values were 1.6 +/- 0.4 ng/ml (n = 131). No progesterone increments were observed in isolated animals, and serum concentrations remained at baseline levels. These limited observations suggest that female leopards do not require intromission to induce ovulation and luteal function. The average interval between oestradiol peaks for cycles with no progesterone increment was 3.4 weeks (range 1-6 weeks). The interval for the 3 complete cycles associated with elevated progesterone concentrations was 7.3 weeks. Analysis of sexual behaviours over the 5-year study period revealed no evidence of seasonality in these captive leopards. PMID- 3339598 TI - Isolated subpopulations of mass-harvested pig oocytes and their characterization by size, incidence of atresia and competence to mature in culture. AB - Pig oocytes were hand collected after follicular puncture or were mass harvested with stainless-steel screens and purified on sucrose density gradients. Most oocytes obtained by mass harvesting with a 75 micron screen and selecting on a 0 and 30% discontinuous sucrose gradient were meiotically incompetent and atretic after culture. Two enriched populations of oocytes were isolated from the 0-15% and 15-30% interfaces with a 106 micron screen and a 0%, 15% and 30% 2-step discontinuous sucrose gradient. These oocyte populations differed significantly in size (P less than 0.001, t test) and in meiotic competence. More than 50% of the larger oocytes matured compared with 14% of the smaller oocytes (P less than 0.002). Of the larger oocytes, 21% progressed beyond meiotic metaphase I, whereas all of the maturing small oocytes were arrested at first metaphase after culture (P less than 0.002). Yields were 45 times greater for oocytes mass harvested with a 106 microns screen and a 15% sucrose density gradient than for oocytes hand collected in the same period of time. Layering these mass-harvested oocytes over a second 15% sucrose gradient or hand sorting the mass-harvested oocytes after culture increased the proportion of maturing oocytes compared with oocytes which were mass harvested before culture and produced higher proportions of oocytes at telophase I or beyond (P less than 0.002). The results demonstrate that mass harvesting of pig oocytes is more efficient than hand selection, and that oocytes collected and selected in this way are at least as capable of meiotic maturation as are oocytes hand selected before culture. PMID- 3339599 TI - Nucleolus organizer regions and nucleoli in preattachment bovine embryos. AB - Embryos (1-cell to elongated blastocyst stage) were recovered from superovulated heifers at surgery (Days 2-4; oestrus = Day 0), after slaughter (Day 4), or by transcervical flushing (Days 6, 7 and 14). The 175 embryos were cultured for 4, 8, 24 or 48 h, fixed on slides and sequentially stained with Giemsa and silver nitrate. Twenty-three 2-cell to blastocyst-stage embryos were fixed, embedded and examined by transmission electron microscopy. Argentophilic nucleolus organizer regions (Ag-NORs), indicative of transcriptionally active rRNA genes, were observed in embryos in which short- or long-term culture began at or after the late 8-cell stage. The nucleoli of embryonic cells also showed increased affinity for silver from the 8-cell stage onward. Differences in the number of Ag-NORs observed after the 8-cell stage reached statistical significance only when Day-5 and Day-7 embryos cultured for 4 h were compared. Ultrastructurally, the nucleoli were seen to develop from small, dense, fibrillar masses at the 2-cell stage, to ring-shaped structures (signifying a low level of activity) at the 8-cell stage. At the 16-cell stage the nucleoli became reticulated, suggesting an increase in activity, and by the morula and blastocyst stages they were characteristic of fully active nucleoli. It is concluded that a significant transcriptional activity of the rRNA genes in the embryos of cattle begins around the 8-cell stage. PMID- 3339600 TI - Ovarian function in the captive black mastiff bat, Molossus ater. AB - In nearly all animals from a laboratory breeding colony that were examined (85/86) the right ovary was significantly larger than the left. Although primordial follicles were present in both ovaries, Graafian follicles and CL were noted only in the right ovary. The left ovary usually had a much less prominent intraovarian vascular supply, and it is suggested that this may play a central role in limiting the ability of follicles to grow on that side. Many of the bats examined very soon after the introduction of stud males had well-developed CL, sometimes of 2-3 different ages, and uteri that had probably been subjected to stimulation by luteal hormones. Such observations made on females that had been housed with a stud male only for 24 h indicate that the black mastiff bat is a spontaneous ovulator with a functional luteal phase. It was common to observe an extended period after the introduction of a stud male during which spermatozoa were present in the vaginal smears from a female almost every day. Most of the ovulations that resulted in pregnancies appear to have occurred during this period. Of the 72 bats with CL, 11 possessed 2 or more CL of the same age, indicating that multiple ovulations can sometimes take place. The right ovaries of all females examined during advanced pregnancy had non-atretic, vesicular or Graafian follicles in addition to the CL of pregnancy. PMID- 3339601 TI - Novel type of potential anticancer agents derived from chrysophanol and emodin. Some structure-activity relationship studies. PMID- 3339602 TI - Analgesic dipeptide derivatives. 4. Linear and cyclic analogues of the analgesic compounds arginyl-2-[(o-nitrophenyl)sulfenyl]tryptophan and lysyl-2-[(o nitrophenyl)sulfenyl]tryptophan. AB - The syntheses of Trp(Nps)-Arg-OMe.HCl (15) [Trp(Nps) = 2-[(o nitrophenyl)sulfenyl]tryptophan], its three stereoisomers, and their corresponding cyclic analogues are reported. The preparation of Trp(Nps)-Lys-OMe (19) and its cyclic analogue is also described. All these compounds have been designed as analogues of the analgesic dipeptide derivatives X-Trp(Nps)-OMe (1b, X = Arg; 2b, X = Lys). In the case of dipeptides containing Arg or D-Arg, the coupling reactions were achieved via the isobutyl chloroformate and N methylmorpholine mediated mixed anhydride procedure, while in the case of the Lys analogue, the N,N-dicyclohexylcarbodiimide method was employed. Sulfenylation reactions were carried out with Nps-Cl in acidic media. Cyclization to the diketopiperazines was achieved by using acetic acid as catalyst. The antinociceptive effects of all these new Trp(Nps)-containing dipeptides were evaluated after icv administration in mice, and the effects were compared with those of 1b, 2b, Tyr-Arg (Kyotorphin), and Tyr-D-Arg. The most active compounds, 15 and 19, were found to exhibit a naloxone-reversible antinociceptive effect similar to those of 1b and 2b and approximately 50 and 12.5 times higher than those of Kyotorphin and its D isomer, respectively. Trp(Nps)-D-Arg-OMe.HC1, D Trp(Nps)-Arg-OMe.HC1, and cyclo[Trp(Nps)-Arg].HC1 were also more effective than Kyotorphin (5, 10, and 10 times, respectively). In view of the structure-activity relationships obtained, several similarities between this series of Trp(Nps) containing dipeptides and that of Kyotorphin analogues have emerged. PMID- 3339604 TI - (R)-(-)-10-methyl-11-hydroxyaporphine: a highly selective serotonergic agonist. AB - Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1 phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n propylamino)tetralin. PMID- 3339603 TI - Crystal structures and pharmacologic activities of 1,4-dihydropyridine calcium channel antagonists of the isobutyl methyl 2,6-dimethyl-4-(substituted phenyl) 1,4-dihydropyridine-3,5-dicarboxylate (nisoldipine) series. AB - A series of isobutyl methyl 2,6-dimethyl-4-(X-substituted phenyl)-1,4 dihydropyridine-3,5-dicarboxylates (X = H, 2-NO2, 3-NO2, 3-CN, 3-MeO, 4-F, 2-CF3, 3-CF3, and 4-Cl) related to and including nisoldipine (X = 2-NO2) has been synthesized, their solid-state structures determined by X-ray analysis (X = H, 2 NO2, 3-NO2, 3-CN, 3-MeO, and 4-F), and their pharmacologic activities determined, as the racemic compounds, against [3H]nitrendipine binding and K+-depolarization induced tension responses in intestinal smooth muscle as measures of Ca2+ channel antagonist activity. Comparisons of structure are presented to previously analyzed 1,4-dihydropyridines. The degree of 1,4-dihydropyridine ring puckering is dependent on the nature and position of the phenyl ring substituent and the adopted interring conformation. Different ester substituents affect 1,4 dihydropyridine ring puckering to a small extent in most cases. Pharmacologic and radioligand binding activities for the nine compounds studied show a parallel dependence on phenyl ring substituent, but the compounds are approximately 10 fold more active in the radioligand binding assay than in the pharmacologic assay. Consistent with a previous report for the nifedipine series (Fossheim et al. J. Med. Chem. 1982, 25, 126), pharmacologic activity increases with increasing 1,4-dihydropyridine ring planarity. PMID- 3339605 TI - Nitrosoimidazoles: highly bactericidal analogues of 5-nitroimidazole drugs. AB - It is believed that metronidazole and related 5-nitroimidazoles are activated by reduction of the nitro group and that the active species has a nitrogen functionality of intermediate oxidation state. However, the preparation and isolation of the active forms of the 5-nitroimidazoles used therapeutically have proven elusive. To pursue this problem we have prepared both 1-methyl-4-phenyl-5 nitrosoimidazole (3) and 1-methyl-4-nitroso-5-phenylimidazole (5) from 4(5) nitroso-5(4)-phenylimidazole (1). We have also prepared the homologous nitroimidazoles. Escherichia coli mutants with defects in DNA repair were found to be sensitive to both 1-methyl-4-phenyl-5-nitroimidazole (4) and metronidazole, but fairly resistant to 1-methyl-4-nitro-5-phenylimidazole (6), a finding in accord with the relative biological activity of 4- and 5-nitroimidazoles examined previously. In contrast, all three nitroso compounds are considerably more bactericidal than their analogous nitro compounds under both aerobic and anaerobic conditions, a finding that provides direct evidence that reduction of the nitro group is responsible for activation of the nitroimidazoles. Further evidence is also consistent with the possibility that the nitrosoimidazoles are themselves biologically active species derived from nitroimidazoles, although a more conservative interpretation is simply that they are more facilely converted to such active species. PMID- 3339606 TI - Synthesis and antiviral activity of various 3'-azido analogues of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1, HTLV-III/LAV). AB - Various 3'-azido analogues of pyrimidine deoxyribonucleosides have been synthesized and tested against human immunodeficiency virus (HIV-1, HTLV-III/LAV) in human peripheral blood mononuclear cells. Among these compounds, the 3'-azido analogues of thymidine (2), 3-(3-oxo-1-propenyl)thymidine (21), 2'-deoxyuridine (1), 2'-deoxy-5-bromouridine(5), 2'-deoxy-5-fluorocytidine (19), 2'-deoxy-5 iodouridine (6), 2'-deoxycytidine (18), 2'-deoxy-5-fluorouridine (4), 2'-deoxy-5 thiocyoanatouridine (16), 2'-deoxy-5-methylcytidine (20), 2'-deoxy-5-aminouridine (7), and 2'-deoxy-5-hydroxyuridine (10) were found to have significant antiviral activity, with EC50 values of 0.002, 0.01, 0.2, 1.0, 1.0, 1.1, 1.2, 4.8, 5.1, 5.1, 6.2, and 10 microM, respectively. The structure-activity relationships are discussed. PMID- 3339607 TI - 6-[18F]fluorometaraminol: a radiotracer for in vivo mapping of adrenergic nerves of the heart. AB - The false neurotransmitter metaraminol has been 18F labeled and evaluated as a possible heart imaging agent on the basis of its selective accumulation in adrenergic nerves. Reaction of 6-(acetoxymercurio)-N-t-BOC-metaraminol with acetyl hypofluorite followed by removal of the BOC group provides a regiospecific synthesis of 6-fluorometaraminol (4). Use of acetyl hypo[18F]fluorite gives [18F] 4 in 60 min in 20-42% radiochemical yield. Systemic blockade of the neuronal uptake-1 carrier with desmethylimipramine or systemic destruction of the adrenergic nerves with 6-hydroxydopamine lowers [18F]-4 accumulation greater than or equal to 85% in all four regions of the rat heart. These preliminary findings suggest that [18F]-4 could be used to assess neuronal damage in various heart diseases by positron emission tomography. PMID- 3339608 TI - Adenosine deaminase inhibitors. Synthesis and biological activity of deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine. AB - Two new deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, 1), 7 deaza-EHNA (6) and 1,3-dideaza-EHNA (11), were synthesized and evaluated for adenosine deaminase (ADA) inhibitory activity and compared with EHNA, 1-deaza EHNA (2), and 3-deaza-EHNA (3). Substitution of a methine group for a nitrogen atom in the 7-position of the purine moiety of EHNA produces a dramatic drop in the inhibitory activity (Ki = 4 X 10(-4) M) whereas compounds 2 and 3 are still good inhibitors (Ki = 1.2 X 10(-7) M and 6.3 X 10(-9) M respectively). EHNA and its deaza analogues so far synthesized were also tested in vitro for their antiviral and antitumor activity in a range of cellular systems. EHNA and 1-deaza EHNA are equiactive as inhibitors of human respiratory syncytial virus (HRSV) replication (MIC = 6.25 micrograms/mL) while the other compounds are inactive. On the other hand, all the examined compounds displayed an antitumor activity comparable to that of the reference compound 1-beta-D-arabinofuranosyladenine (ara-A), 7-deaza-EHNA being the most active of all. The results obtained showed that there is no correlation between adenosine deaminase inhibition and antiviral or antitumor activity in this series of compounds. 3-Deaza-EHNA, the most active inhibitor of ADA among the EHNA deaza analogues, greatly potentiates the antitumor activity of ara-A in vitro. In vivo activity was observed only when the two compounds were used in combination. PMID- 3339609 TI - 1-Amino-substituted 4-methyl-5H-pyrido[4,3-b]indoles (gamma-carbolines) as tricyclic analogues of ellipticines: a new class of antineoplastic agents. AB - A series of 1-amino-substituted 4-methyl-5H-pyrido[4,3-b]indoles that are structurally related to ellipticines by deletion of a ring have been synthesized in order to evaluate their DNA affinity, their in vitro cytotoxicity on L1210 cultured cells, and their in vivo antitumor activity. Among 24 derivatives that have been prepared and studied for the structure-activity relationship in this new class of antineoplastic agents, those that have a NH(CH2)3N(R)2 side chain (R = CH3 or C2H5) at their 1-position, a 4-methyl group, and an 8-OH substituent, either with a 5-NH or with a 5-NCH3 group, show the most potent cytotoxicities on L1210 cultured cells and in vivo antitumor properties in P388 and L1210 leukemia systems. In vivo antineoplastic activity of the most potent products was confirmed in P388 and L1210 leukemia systems. In vivo antineoplastic activity of the most potent products was confirmed on other mouse experimental tumors from the standard NCI screening:B16 melanoma and C38 adenocarcinoma. PMID- 3339610 TI - Synthesis and biological evaluations of certain 2-halo-2'-substituted derivatives of 9-beta-D-arabinofuranosyladenine. AB - The synthesis of a series of 2-chloro- or 2-fluoro-9-(2-substituted-2-deoxy-beta D-arabinofuranosyl)adenines (4g-n) is described. New compounds were prepared from either 2-chloroadenosine or 2-fluoroadenosine by first blocking the 3'- and 5' hydroxyls as the tetraisopropyldisiloxane derivatives. Activation of O-2' by formation of a triflate followed by nucleophilic displacement allowed introduction of various groups in the proper configuration at C-2'. Fluoride ion treatment then produced the deblocked nucleosides. All of the new compounds were evaluated as cytotoxic agents against L1210 and H.Ep.-2 cells and as antiviral agents against herpes simplex viruses 1 and 2 and vaccinia virus in culture. PMID- 3339611 TI - Structure-activity relationship in PAF-acether. 4. Synthesis and biological activities of carboxylate isosteres. AB - The synthesis and biological characterization of some 3-carboxylate isosteres of PAF-acether structurally modified in positions 1 (ether, carbamate), 2 (acetoyl, ethoxy), and 3 (chain length and polar head group) are reported. All derivatives present antagonist activities against PAF-acether-induced effects in vitro (platelet aggregation) and in vivo (bronchoconstriction and thrombocytopenia in guinea pig and, to a lesser extent, hypotension in rat). The functional modifications presented here do not modify dramatically the potency of antagonist activities, and there is no enantioselectivity. All of the isosteres are specific PAF-acether antagonists, except the 1-carbamoyl analogue, which is also potent against acetylcholine-induced hypotension and bronchoconstriction. PMID- 3339612 TI - Angiotensin-converting enzyme inhibitors. 2. Perhydroazepin-2-one derivatives. AB - alpha-[(3S)-3-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2-oxo-6 or 7 phenylperhydroazepin-1-yl]acetic acids (monoester monoacids) and their dicarboxylic acids were synthesized, and their angiotensin-converting enzyme (ACE) inhibitory activities were evaluated. The dicarboxylic acids having phenyl substituents at the 6R, 6S, and 7S positions on the azepinone ring showed potent inhibition in vitro. The corresponding monoester monoacids, when administered orally, suppressed the pressor response to angiotensin I administered intravenously. The monoester monoacids having the phenyl substituent at the 6 position showed a longer duration of action than one having the substituent at the 7-position. The structure-activity relationship was studied on the basis of the conformational energy calculation. PMID- 3339614 TI - (8 beta)-Ergoline-8-carboxylic acid cycloalkyl esters as serotonin antagonists: structure-activity study. AB - A series of (8 beta)-6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid cycloalkyl esters were prepared and examined for blockade of vascular 5HT2 receptors. The antagonist in this series that had the highest 5HT2 receptor affinity was (8 beta)-6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid cyclohexyl ester. This compound was therefore chosen as the basic backbone of a structure-activity study to determine what effect different N1-substituents, N6 substituents, and ester ring substituents had on 5HT2 receptor affinity. Maximal 5HT2 receptor affinity was obtained when the N1-substituent was isopropyl, the N6 substituent was methyl, and there was a hydroxy or keto substituent in the 4 position of the ester cyclohexyl ring. PMID- 3339613 TI - Conformational and steric aspects of the inhibition of phenylethanolamine N methyltransferase by benzylamines. AB - Compounds of the benzylamine (BA) class are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). Restriction of the aminomethyl side chain through its incorporation into a cyclic framework as in 1,2,3,4-tetrahydroisoquinoline (THIQ) or 2,3,4,5-tetrahydro-1H-2-benzazepine (THBA) results in enhanced potency as an inhibitor, suggesting a conformational effect in the binding of BAs to the active site; however, these ring systems still retain a high degree of flexibility. We have synthesized a series of conformationally defined analogues of benzylamine in order to probe the effect of conformation, as well as the influence of steric bulk, on PNMT inhibition by this class of ligands. In addition, 1-, 3-, and 4-methyl-substituted THIQs were synthesized and evaluated as flexible models for steric bulk tolerance about this ring system. Substitution by a methyl group on either benzylic position of THIQ results in diminished activity as a PNMT inhibitor; however, 3-methyl-THIQ shows enhanced activity as an inhibitor vs THIQ itself. Full conformational restriction of the BA side chain in analogues 4-8 results in a dramatic loss in inhibitor potency. We attribute this effect to a negative steric interaction between the alkyl bridging units above (or below) the heterocyclic ring systems and an active site amino acid residue. Conformational restriction of THIQ employing a bridging unit that is not located above (or below) the ring system results in only slightly diminished activity compared to THIQ itself. The relative activities of 4-8 were examined in terms of the conformational descriptors tau 1 and tau 2. Although there is no correlation between tau 1 and activity as a PNMT inhibitor, a qualitative relationship between tau 2 (endo or exo) and activity with PNMT is apparent. We believe that the binding of the N-H and/or N-lone pair of electrons may influence the spatial orientation of these molecules at the active site, resulting in positive binding interactions for compounds 4 and 8 and negative interactions for analogues 5-7. The results from the current investigation are compared to those obtained from a similar study involving conformationally defined amphetamines. PMID- 3339615 TI - Inhibition of murine thymidylate synthase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin. AB - A series of 5,8-dideaza analogues of folic acid, isofolic acid, aminopterin, and isoaminopterin were evaluated for inhibition of thymidylate synthase, TS, from mouse L1210 leukemia cells with 10-propargyl-5,8-dideazafolic acid, CB3717, 4a, as the reference inhibitor. These compounds were also tested as inhibitors of human dihydrofolate reductase, DHFR, obtained from WIL2 cells. None of the analogues studied were as potent as 4a toward TS; however, 9-methyl-5,8 dideazaisoaminopterin, 6d, was only 2.5-fold less effective. Compound 4a was prepared by direct alkylation of the di-tert-butyl ester of 5,8-dideazafolic acid followed by hydrolysis of the resulting diethyl ester, which resulted from concomitant transesterification. It was found to be identical with a sample of 4a prepared by earlier methodology by using a variety of spectroscopic techniques. Its isomer, 9-propargyl-5,8-dideazaisofolic acid, 4b, which was synthesized by an analogous approach, was found to be dramatically less inhibitory toward TS than 4a. Each of the 2,4-diamino derivatives, including those possessing an allyl or propargyl group at N9, was an excellent inhibitor of DHFR, having a level of potency similar to that of methotrexate, MTX. However, many of these 5,8 dideazaaminopterin analogues were far more inhibitory toward TS than MTX. PMID- 3339616 TI - Imidazole-pyridine bioisosterism: comparison of the inotropic activities of pyridine- and imidazole-substituted 6-phenyldihydropyridazinone cardiotonics. AB - We previously reported the structure-activity relationships (SAR), molecular structure, pharmacology, and molecular pharmacology of indolidan (LY195115), a potent and long-acting dihydropyridazinone cardiotonic. Our 6 phenyldihydropyridazinone SAR studies revealed the critical nature of the substituent at the para position of the phenyl ring. An acetamido substituent provided potent cardiotonic activity and we hypothesized that this may relate to the ability of the acetamide carbonyl to function as a hydrogen-bond acceptor. To further address this question, we prepared 15 (4,5-dihydro-6-[4-(3 pyridinyl)phenyl]-3(2H)-pyridazinone), the 3-pyridyl analogue of imazodan. As is the case with imazodan, this (pyridylphenyl)dihydropyridazinone possesses a nitrogen three atoms removed from the phenyl ring, but the molecular framework through which it is attached to the phenyldihydropyridazinone moiety is altered. After iv administration to pentobarbital-anesthetized dogs, inotropic ED50 values of 15, imazodan, and the parent compound, 4,5-dihydro-6-phenyl-3(2H) pyridazinone, were 19.4, 50.1, and 6330 micrograms/kg, respectively. Thus, 15 is over 2-fold more potent than imazodan and 326-fold more potent than the parent, unsubstituted compound. These data, as well as data obtained with other congeners, are consistent with the hypothesis that a suitably oriented hydrogen bond-acceptor site contributes to the high degree of inotropic potency observed with these dihydropyridazinone cardiotonics. PMID- 3339617 TI - Pyrido[2,1-b]quinazolinecarboxamide derivatives as platelet activating factor antagonists. AB - A series of N-[(heteroaryl)alkyl]pyrido[2,1-b]quinazolines were evaluated for their ability to inhibit the binding of radiolabeled platelet activating factor (PAF) to its receptor on dog platelets. The most potent compounds in this series were found to be pyrido[2,1-b]quinazoline-8-carboxamides possessing a four- or six-carbon chain between the carboxamide nitrogen atom and a 3-pyridinyl or 5 pyrimidinyl moiety. Since earlier metabolism studies with pyridoquinazolinecarboxamides suggest that the carboxamide moiety is labile to hydrolysis in vivo, attempts were made to find isosteric replacements for this group. The substitutions examined led to a loss of activity; however, insertion of a methyl group on the carbon atom alpha to the carboxamide nitrogen led to an enantioselective enhancement of potency. (R)-2-(1-Methylethyl)-N-[1-methyl-4-(3 pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (34) was more potent than the corresponding S enantiomer in the PAF binding assay and was also shown to be more resistant to degradation by amidases present in whole liver homogenates obtained from guinea pig, dog, and squirrel monkey. The corresponding rac-2-(1-methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1 b]quinazoline-8-carboxamide (33) was found to inhibit transient PAF-induced thrombocytopenia and decreases in blood pressure in guinea pigs after intravenous or oral administration and to have a duration of action of greater than 5 h after an oral dose of 200 mg/kg. Compound 33 thus represents the prototype of a new class of orally active PAF antagonists. PMID- 3339618 TI - Cardioactivity and solid-state structure of two 4-isoxazolyldihydropyridines related to the 4-aryldihydropyridine calcium-channel blockers. AB - Diethyl 2,6-dimethyl-4-(5-ethyl-3-phenylisoxazol-4-yl)-1,4-dihydroyprid ine-3,5- dicarboxylate (5) and diethyl 2,6-dimethyl-4-(5-isopropyl-3-phenylisoxazol-4-yl) 1,4-dihydropyri dine-3,5- dicarboxylate (6) were synthesized, and their molecular structures were determined by X-ray crystallography. In compound 5, which has an ethyl group at the C5 position of the isoxazole ring, the deviation from planarity in the dihydropyridine (DHP) ring is the smallest of all known DHP derivatives. The dihedral angle between the aromatic ring (the isoxazole) and the DHP ring, which is approximately 90 degrees in similar biologically active dihydropyridines, is somewhat smaller (82.7 degrees and 85.2 degrees, respectively) in these two compounds. In both compounds, one of the ester groups is coplanar with the DHP ring while the other one is out of plane by 14.7 degrees (ethyl) and 18.8 degrees (isopropyl). Both 5 and 6 were found to be vasodilators in the Langendorff assay. The potency of 6 on cardiac flow was similar to that of nifedipine; however, that of 5 was considerably attenuated. Since isoxazolyl analogue 6 lacks the significant negative inotropic activity associated with nifedipine, 6 offers promise as an antihypertensive or antianginal agent. PMID- 3339619 TI - Synthesis and antiviral evaluation of carbocyclic analogues of 2'-azido- and 2' amino-2'-deoxycytidine. AB - Carbocyclic analogues of 2'-azido- and 2'-amino-2'-deoxycytidine, compounds 8 and 9, were synthesized by an eight-step synthesis from (+/-)-(1 alpha,2 alpha,3 beta,5 beta)-3-amino-5-(hydroxymethyl)-1,2- cyclopentanediol (1), which was prepared from cyclopentadiene via an eight-step route. These compounds were tested in vitro against herpes simplex virus type 1 (HSV-1). The 2'-amino analogue was found to show moderate antiviral activity, with an ED50 of 50 microM. However, the 2'-azido analogue was not active at a concentration up to 400 microM. PMID- 3339621 TI - Supply and demand: lessons from dental medicine? PMID- 3339620 TI - 2-Methyl-1,3-dioxaazaspiro[4.5]decanes as novel muscarinic cholinergic agonists. AB - Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical assessment of analogues of AF-30 designed to have sufficient conformational freedom to allow greater receptor flexibility and hence activation. The new compounds and important standards were tested in a new biochemical assay designed to measure both receptor affinity and intrinsic activity of each compound and for their ability to stimulate phosphatidylinositol turnover in rat cerebral cortex. Two azaspirodecanes (5a and 5b) were shown to have far greater predicted efficacy than AF-30. PMID- 3339622 TI - Congressional concerns about physician supply. PMID- 3339623 TI - Using review of medical clinic charts to teach occupational health. AB - The authors evaluated the effectiveness of chart audit with written feedback as a tool for encouraging second- and third-year residents to obtain and record occupational information during history-taking. Baseline information was obtained by reviewing the charts of 20 residents of patients who presented for complete history-taking and physical examination and scoring for various aspects of occupational history-taking. Intervention was directed at 10 of the residents; the other 10 served as controls. Between five and 12 charts were reviewed for each of the 10 residents in the intervention group; the scoring sheet, scoring criteria, results, and a brief discussion of potentially relevant occupational concerns for the given patient were returned to the resident, along with copies of the relevant pages of the patient's record. Chart review showed no difference in total scores for occupational history-taking between the two groups before intervention. The postintervention scores improved insignificantly for the intervention group; however, the scores deteriorated significantly for the control group (1.38 to 0.92, .05 greater than p greater than .025). PMID- 3339624 TI - The need for an ethical code for teachers of the basic biomedical sciences. PMID- 3339625 TI - Analysis of changing answers on multiple-choice examination for nationwide sample of Canadian psychiatry residents. PMID- 3339626 TI - A comparison of attitudes toward geriatrics among medical residents. PMID- 3339627 TI - Comparison of two formats for a psychiatry clerkship. PMID- 3339628 TI - International Medical Scholars Program. PMID- 3339629 TI - Clinical impressions. PMID- 3339630 TI - Small-group instruction. PMID- 3339631 TI - The Scylla and Charybdis of medical education. PMID- 3339632 TI - Alan Gregg memorial lecture. The rising supply of physicians and the pursuit of better health. PMID- 3339633 TI - Antigens involved in resistance to mucosal association by Vibrio cholerae. AB - Resistance to growth of Vibrio cholerae at the mucosa of blind intestinal loops developed in rats after intestinal or parenteral exposure to live organisms or other antigenic materials. Simultaneous serological studies suggested that neither serum vibriocidal activity nor intestinal mucus antibodies are likely to provide a direct test of antibacterial immune status. Challenge of rats 4 weeks after one dose of antigen may reveal a form of immunity that is not related to antibodies in the intestine and possibly is analogous to long-term immunity expressed in man following infection with the organism. This immunity has not been attributed to lipopolysaccharide (LPS) antigen and does not appear to involve flagella-associated antigens; involvement of antigens other than LPS, such as protein antigens of the outer membranes of V. cholerae, has not yet been substantiated. Separation of monomeric sub-units of outer-membrane proteins by hydrophobic interaction high pressure liquid chromatography has revealed significant quantitative differences among preparations derived from the common serotypes of the organism. These differences may be sufficient to explain the better protection observed when homologous serotypes were used for immunisation and challenge in the long-term resistance model. PMID- 3339635 TI - Morphological changes in the oral (buccopharyngeal) membrane in urodelan embryos: development of the mouth opening. AB - The ultrastructure of the oral (buccopharyngeal) membrane in the embryo of the urodelan, Hynobius tokyoensis, was examined by transmission (TEM) and scanning electron microscopy (SEM). The oral membrane consists of the stomodeal ectoderm and foregut endoderm, and is three to five cell layers thick at stage 24. The oral membrane gradually thickens as development proceeds. The stomodeal collar, derived from the ectoderm, is folded inward along the foregut endoderm. Tooth germs are formed partly by cells of the stomodeal collar and partly by mesenchymal cells and calcification takes place before hatching. Secretory granules, which are markers of epithelial differentiation, appear in some cells of the foregut endoderm. Within the oral membrane, the cells of the stomodeal collar become the basal cells, and the endodermal cells of the foregut become the apical cells of the future oral epithelium. Gaps are formed by the epithelial differentiation of the endodermal cells of the foregut in the oral membrane. The gaps connect with each other, with the stomodeum, and with the foregut. As a result of these events, the mouth opens at stage 43, just after hatching. PMID- 3339634 TI - The prevalence of antibody to human parvovirus B19 in England and Wales. AB - The prevalence of antibody to human parvovirus B19 (anti-B19 IgG) in England and Wales was measured by an antibody-capture radioimmunoassay. Over 2000 sera were examined; 1422 from the general population, 374 from unselected children admitted to hospital and 300 from women attending an antenatal clinic. Waning levels of maternally-derived antibody were found in infants under 1 year old. In children 1 5 years old, 5-15% had anti-B19 IgG and this rose to 50-60% in older children, young adults and women of child-bearing age. In older people, the prevalence of anti-B19 IgG increased with age, rising to more than 85% in those over 70 years old. PMID- 3339636 TI - Rising incidence of breast cancer. PMID- 3339637 TI - Evaluation of data from long-term rodent studies. PMID- 3339638 TI - Projections of lung cancer mortality in the United States: 1985-2025. AB - Lung cancer has been the leading cause of cancer death in the United States for the larger part of this century. Increases in smoking prevalence from the 1900s through the 1950s have resulted in more than 100,000 deaths annually. Because of the changes during the last three decades in smoking prevalence, the decreasing tar content of cigarettes, and the increasing popularity of low-tar cigarettes, trends in lung cancer are difficult to predict. This article presents an analysis of smoking and lung cancer data using an age-period-cohort model for projecting lung cancer mortality through the year 2025. The projections are based on the initial parameterization of the model and on prevention objectives related to smoking behavior established by the National Cancer Institute. It is concluded that the recent trends in lung cancer are unlikely to be affected by changes in cigarette composition and consumption in the near term, but increasing the effectiveness of anti-smoking campaigns can have a considerable effect on lung cancer rates in the more distant future. PMID- 3339640 TI - Tobacco liability litigation as a cancer control strategy. PMID- 3339639 TI - Chemotherapeutic evaluation using clinical criteria in spontaneous, autochthonous murine breast tumors. AB - Six drugs, three of which are considered to be active against human breast cancer [melphalan (PAM), cyclophosphamide (CTX), and 5-fluorouracil (FUra)] and three of which have failed to demonstrate activity against human breast cancer [N phosphonacetyl-L-aspartate (PALA), cytarabine (ara-C), and 6-thioguanine (TG)], were tested at optimal weekly doses in (BALB/-cfC3H X DBA/8)F1 (CD8F1) mice bearing spontaneous, autochthonous breast tumors averaging 300 mg. When treatment was evaluated by laboratory criteria (i.e., tumor growth inhibition in comparison to vehicle-treated, size-matched controls), all six of the drugs tested were judged to be active. However, when the criteria for positive drug activity consisted of the attainment of tumor regressions of greater than or equal to 50% in greater than or equal to 20% of the treated individuals (i.e., analogous to clinical criteria), only the three drugs that are known to be active against human breast cancer (PAM, CTX, and FUra) were judged active against the spontaneous murine breast tumors. PALA, ara-C, and TG failed to demonstrate regressing activity against the spontaneous murine breast tumors. With a caveat concerning the limited spectrum of drugs evaluated in this study, it can be concluded that the CD8F1 breast tumor model demonstrated 100% correlation with human breast cancer in terms of both positive and negative drug sensitivity when the criteria for evaluation were parallel. PMID- 3339641 TI - Medical school admission: then and now. PMID- 3339643 TI - Need for victimization screening in a black psychiatric population. AB - Recent reports indicate that violence toward others is a major public health problem in the black community; however, there are very few empirical studies that delineate the severity of the problem. In an effort to add to the meager data on violence in the black community, the authors compiled the results of a victimization screening form obtained from a black outpatient psychiatric population. Recommendations are made that black psychiatric populations be screened for histories of victimization, as victimization is common in this population group and will have a significant impact on treatment. PMID- 3339642 TI - Parental educational background and residency training selection of minority and nonminority medical students. AB - The subject of background variables influential in the choice of postgraduate medical specialty training has been described in numerous papers. Few, if any, have examined the influential patterns in minority students' residency training selection when compared with nonminority students. No studies reviewed examined the differential patterns that may have an impact on specialty selection in these subgroups, especially in regard to maternal and paternal educational status. This study analyzes the interrelationship between minority and nonminority medical students, their parental educational background, and selection of postgraduate specialty, and suggests that parental educational background be investigated further as a predicative indicator of medical student specialty career selection. PMID- 3339644 TI - Alcohol increases mortality in murine head injury. AB - Head injury is a major factor in the mortality of traumatized patients, accounting for about 50 percent of the resulting fatalities. Alcohol intoxication is frequently (25 to 50 percent) associated with head injuries. This study was undertaken to investigate the effects of alcohol on head trauma in a standardized animal model. Swiss Webster mice (25 +/- 2 g) were given intraperitoneally 0.2 mL of either saline or 50 percent ethanol in saline. Thirty minutes later, under light ether anesthesia, severe concussion was produced by dropping a 39.5-g lead weight from a height of 30 cm. The trauma was centered on the midskull by channeling the weight through a vertical tube, 1.2 cm in diameter. Animals were observed daily for eight days. Among the controls, 12 of 12 mice, (100 percent) survived for four days and 8 of 12 (67 percent) survived eight days. In the alcohol recipients, there were 10 of 21 survivors (48 percent) at four days and only one survivor (5 percent) at eight days. This study clearly demonstrates that alcohol increases the lethality of standardized head trauma in mice. The mechanism by which alcohol modifies the effects of craniocerebral trauma remains to be elucidated. PMID- 3339645 TI - Acute effect of decaffeinated coffee on heart rate, blood pressure, and exercise performance in healthy subjects. AB - The effect of decaffeinated coffee on the cardiovascular exercise performance in nine healthy volunteers was evaluated in a double-blind randomized fashion. The heart rate, blood pressure, and duration of exercise were unchanged, and no arrhythmias or ischemic changes were seen on the electrocardiogram after drinking decaffeinated coffee. It was concluded that decaffeinated coffee has no discernible, acute, adverse cardiovascular effects. PMID- 3339646 TI - Guidelines for preparation of a scientific paper. AB - Even the experienced scientific writer may have difficulty transferring research results to clear, concise, publishable words. To assist the beginning scientific writer, guidelines are proposed that will provide direction for determining a topic, developing protocols, collecting data, using computers for analysis and word processing, incorporating copyediting notations, consulting scientific writing manuals, and developing sound writing habits. Guidelines for writing each section of a research paper are described to help the writer prepare the title page, introduction, materials and methods, results, and discussion sections of the paper, as well as the acknowledgments and references. Procedures for writing the first draft and subsequent revisions include a checklist of structural and stylistic problems and common errors in English usage. PMID- 3339647 TI - Mitral valve prolapse and hypertension. PMID- 3339648 TI - Surgical treatment of a large emphysematous bulla complicated by accumulation of fluid and infection. AB - Emphysematous bulla complicated by infection is very rare. A case of a patient, who was a respiratory cripple, with an infected bulla is presented. Surgical resection was performed with excellent results. The treatment of choice is surgery by means of excision of bulla, partial pleurectomy, and decortication of the involved lung. PMID- 3339649 TI - Ethanol modulation of plasma norepinephrine response to trauma and hemorrhage. AB - Does ethanol affect the adrenergic response to trauma? In 52 trauma victims, grouped according to blood ethanol concentrations, we found there was a significantly higher mean plasma norepinephrine (NE) concentration in heavy imbibers than in those with no detectable blood ethanol (790 +/- 84 pg/ml vs. 1,260 +/- 310; p = 0.02). To control confounding variables such as intensity of pain, injury severity, etc., we selected blood loss (0.9% body weight over 15 min), as an aspect of trauma to study in six normal subjects before and after ingestion of 6 oz and 10 oz of 86-proof liquor on successive days. As expected, the increase in plasma NE upon assumption of an upright position was accentuated by blood loss, (384 +/- 43 pg/ml prebleed; 694 +/- 16 post-bleed; p = 0.001). The postural or hypovolemic effect on plasma NE was enhanced by ingestion of ethanol at 6 oz prebleed (529 +/- 42 pg/ml pre-ethanol vs. 732 +/- 64 post ethanol; p = 0.02) or at 10 oz post-bleed (694 +/- 16 pg/ml vs. 1,154 +/- 166; p = 0.04). There was an approximate dose-response effect of ethanol on plasma NE under all conditions; for example, post-bleeding upright NE: 717 +/- 57, no ethanol; 1,045 +/- 221, 6 oz ethanol, and 1,257 +/- 182, 10 oz ethanol. Plasma epinephrine concentrations were not significantly affected by positional changes, blood loss, or ethanol consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339651 TI - Incomplete fractures associated with penetrating trauma: etiology, appearance, and natural history. AB - Patient charts and radiographs of 12 patients noted to have an incomplete fracture due to a penetrating injury were reviewed to evaluate the natural history of these fractures. One cortical chip fracture was due to a stab wound; the remainder were due to low-energy handguns. Morphologically, two patterns existed: drill hole fractures through the central metaphyseal region of long tubular bones, and divot fractures of the margins of long bone metaphyses and flat bones. Drill hole fractures and divot fractures complicated by fracture line extension required a weight bearing cast or functional brace while healing. The chip fracture and uncomplicated divot fractures were managed symptomatically. Chip, drill hole, and divot fractures followed a benign course and healed by formation of cortical bone along the defect rim. PMID- 3339650 TI - Knife wounds into the airspaces of the laryngeal trapezium. AB - The trapezoidal-shaped area of the neck bounded by the hyoid bone, cricoid cartilage, and medial borders of the sternocleidomastoid muscles is widely exposed to knife slash and stab injuries. Suicidal or homicidal throat slashes involving this area may produce serious horizontal laryngeal injuries, whereas homicidal stab wounds may produce serious vertical laryngeal or hypopharyngeal injuries. The extent of such injuries often cannot be predicted from the entrance wounds and presenting symptoms. Therefore special guidelines should be followed to insure the safety of selective exploration of knife wounds penetrating into the airspaces within this trapezium. In addition, repair of serious laryngeal injuries may require use of laryngoplasty or partial laryngectomy techniques rather than simple repair. PMID- 3339652 TI - Distally based gastrocnemius myocutaneous flap augmented with an arterial anastomosis--a combination of myocutaneous flap and microsurgery. AB - Microsurgical techniques can augment the arterial blood supply of a distally based myocutaneous flap, by reanastomosis of the sural artery to a main artery of the leg, allowing the flap a greater length and arc of rotation to cover defects of the distal half of the leg. No venous anastomosis is required. This procedure was used in 17 patients with open tibial fractures. They all healed primarily without any early or late complications. The use of this augmented flap provides a simple and reliable method for reconstruction of difficult wounds of the distal lower leg. It is easier and safer than a free flap. PMID- 3339653 TI - Splenic preservation with the use of a stapling instrument: a preliminary communication. AB - Observation, ligation of the splenic artery, repair of the spleen by simple suturing with or without the use of hemostatic agents, omentum, an absorbable net or ladder, and partial splenectomy have all been proposed as a means of preserving the injured spleen. A new technique of partial splenectomy with the use of a stapling instrument is presented. The instrument has been used with success experimentally in dogs and in two patients. PMID- 3339654 TI - Pelvic fracture associated with severe intra-abdominal gynecologic injury. AB - A case report of a complex pelvic fracture with associated severe intra-abdominal gynecologic injury is presented. The injury involved lacerations to the ovary, fallopian tube, and nonpregnant uterus. No previous reports of pelvic fractures with such visceral gynecologic injury have been found. PMID- 3339655 TI - Post-traumatic toxic shock syndrome. AB - Toxic shock syndrome (TSS) associated with Staphylococcus occurs most commonly in menstruating women, although cases in both sexes have been reported. This report describes a severe case of TSS after a relatively minor stab wound. The male patient exhibited all of the major characteristics of this multisystem disease including anuric renal failure. TSS, which can be fatal, may result from surgical and traumatic wound infections and demands prompt recognition and treatment. PMID- 3339656 TI - The erect penis--injury prone organ. AB - Erection converts the safe, flaccid penis into a vulnerable organ. During erection, the usually thick tunica albuginea becomes very thin and easily fracturable. Penile fracture is an under-reported urologic injury, with only approximately 100 cases reported in the world literature. We report on three cases, one with rupture of one corpus spongiosum and two with rupture of both corpora cavernosa associated with almost complete transection of the urethra. All three cases were treated surgically, with good outcome and no postoperative complications. The authors postulate that some cases of deviation of the penis are actually the result of some minor degree of penile fracture. PMID- 3339657 TI - A method of estimating the extensiveness of lesions (burns and scalds) based on surface area proportions. PMID- 3339658 TI - Evaluation's of advanced trauma life support. PMID- 3339659 TI - Peritoneal lavage in penetrating thoraco-abdominal trauma. AB - Forty-five consecutive patients with penetrating thoraco-abdominal trauma underwent surgical exploration to evaluate the ability of peritoneal lavage to detect peritoneal penetration. Eight patients fulfilled standard criteria for operation and did not undergo lavage. The remaining 37 patients underwent diagnostic peritoneal lavage using a closed technique before exploratory laparotomy. Using 10,000 RBC/mm3 as our previously established criterion for peritoneal penetration, there were seven true positive, one false positive, 28 true negative, and one false negative lavage for an overall accuracy of 94.6% with 87.5% sensitivity and 96.6% specificity as determined by subsequent laparotomy. While 33% of this patient cohort were found to have significant injuries (four had isolated diaphragmatic injuries, all detected by peritoneal lavage), 67% were subjected to negative surgical exploration, as accurately predicted by peritoneal lavage. Negative laparotomy carried a 10.7% operative morbidity. Based on these data we advocate diagnostic peritoneal lavage in patients with thoraco-abdominal penetrating trauma who otherwise lack operative indications. PMID- 3339660 TI - Predictability of splenic salvage by computed tomography. AB - The recognition of overwhelming post-splenectomy infection (OPSI) has led to greater efforts to conserve splenic tissue in patients sustaining blunt torso trauma. Nonoperative management of splenic trauma has emerged as a means to enhance splenic salvage yet criteria to assure the safety of such an approach remain ill defined and controversial. Since severity of injury directly influences outcome, a need exists for identification of splenic injuries that require early operation and repair or removal. Using our recently reported classification of splenic trauma, 46 patients with blunt splenic trauma were evaluated preoperatively with computed tomography (CT). Injuries were graded I through IV and were described as capsular or subcapsular disruptions without parenchymal injury (four); capsular and parenchymal injuries not involving the major vessels or hilum (24); injuries involving major vessels and/or the hilum (17); and fragmentation/devascularizing injuries (one). Additional modifiers were added for associated intra-abdominal and/or extra-abdominal injuries. Sixteen patients had their splenic injuries managed nonoperatively and the remainder underwent operation for the splenic injury or associated injuries. The CT classification was confirmed in all patients and we believe early operation optimized splenic salvage. We conclude that: 1) CT is an accurate technique to determine the extent of splenic injury; 2) CT classification of splenic trauma has a high correlation with anatomic findings and need for operation; 3) early operation in patients with severe class II and all class III injuries affords optimal conditions for splenic salvage; and 4) early definitive management of splenic trauma significantly reduces late splenectomy and shortens hospitalization. PMID- 3339661 TI - The treatment of crotalid envenomation without antivenin. AB - Eighty-one patients were treated for crotalid envenomation over the past 12 years at the Ben Taub General Hospital, Houston. Bites were inflicted by copperheads (56%), water moccasins (15%), and rattlesnakes (12%). In 17% of patients the species of snake was not identified. Using a grading scale of one to four from minimal to severe envenomation, 54% were grade I, 29% grade II, 7% grade III, 6% grade IV, and 4% were not graded because the patients were seen more than 12 hours after envenomation and not evaluated by other physicians. Five patients received one dose (10 cc) of crotalid antivenin each before transfer to our Emergency Center. All patients were treated with intravenous fluids, antibiotics, tetanus prophylaxis, immobilization of the injured part, and elevation of the extremity to the level of the heart. No patients received antivenin or excisional therapy at this institution and one minor digital fasciotomy was performed. There were no deaths or amputations in this series. Eight patients developed superficial necrosis of the skin but only one required a skin graft. Three patients developed hematologic abnormalities and were treated with either platelet transfusions or fresh-frozen plasma. One patient required dopamine for hypotension refractory to fluid resuscitation. This experience supports a conservative approach to venomous snakebites and raises the question about the need to utilize traditional therapy for snakebites caused by species seen in our locality. PMID- 3339662 TI - Behavioral consequences of trauma. AB - A group of 65 head-injured patients, making an apparent good recovery, were studied with the Halstead-Reitan neuropsychological test battery because of personality or cognitive difficulty. A significant relationship was identified between outcome as measured by the Halstead Impairment Index and both Injury Severity Score and Glasgow Coma Scale score. A significant relationship was also found to exist between the Halstead Impairment Index and employment status of the study group. Patients were placed in three groups, depending on their impairment index. Of the complications identified, spinal fracture, pupillary dysfunction, and intracranial pressure elevation were consistently associated with an impaired performance on the neuropsychological testing. These findings suggest that there is a relationship between head injury complications and neuropsychological potential which can cause lingering problems and influence the patient's rehabilitation process. PMID- 3339663 TI - Myocardial contusion in blunt trauma: clinical characteristics, means of diagnosis, and implications for patient management. AB - The incidence, diagnosis, and impact on surgical management of myocardial contusion (MC) are incompletely defined. During a 12-month period, all patients admitted to a Level I trauma center with blunt trauma were prospectively evaluated for MC (n = 1,110). Those with anterior chest wall contusions, sternal or anterior rib fractures, or pain/tenderness of the anterior chest (n = 140, 13%) underwent immediate and daily ECG, and CPK isoenzymes were measured at admission and every 6 hours in the first 24 hours. Eighty-nine of these patients underwent gated ventricular angiography (GVA) and 66 underwent two-dimensional echocardiography (2D ECHO). MC was considered present if either: 1) CPK-MB was greater than or equal to 5% of total CPK, or 2) an abnormal admission ECG reverted to normal before patient discharge. Fifty-six patients (5% of admissions, 40% of those with apparent chest trauma) were positive by one or both criteria. Thirty patients (54%) were positive by CPK alone, 23 (41%) by both CPK and ECG, and three (5%) by ECG alone. Of the 53 with elevated CPK-MB, 14 (26%) were normal on admission with the remainder becoming elevated in the first 24 hours. 2D ECHO was abnormal in only three of 21 positive patients (14%), and GVA was abnormal in only three of 40 positive patients (7%). Surgical procedures requiring general anesthesia were performed in 37 (66%) of the positive patients. No significant arrhythmias developed under general anesthesia. PMID- 3339664 TI - Creatine phosphokinase-MB assays in patients with suspected myocardial contusion: diagnostic test or test of diagnosis? AB - To clarify the role of serum CPK-MB assays in the diagnosis of myocardial contusion, we reviewed the hospital records of 182 patients with significant blunt chest trauma and serial CPK-MB determinations. In our laboratory a serum CPK-MB/CPK ratio less than 2.2% is abnormal. The study group was composed of 131 men and 51 women, with a mean age of 35 years. Only six patients had histories of cardiac disease. Of 159 patients injured in vehicular accidents, 143 were drivers, nine were pedestrians, and seven were passengers. There was no relationship between the MB fraction and soft (nonspecific changes) or strongly suggestive (ectopy, focal changes) ECG signs of myocardial contusion. Two of the three patients with power failure had CPK-MB/CPK ratios less than 2.2%. MUGA scans, performed in 18 patients, indicated myocardial injury in seven patients; only 1/7 had abnormal 2D echocardiography, and only 2/7 had elevated MB fractions. In summary, we found no relationship between serum CPK-MB and the presence of clinically significant myocardial contusion. CPK-MB determination in patients with suspected blunt myocardial injury is unjustifiably expensive ($108/assay) and adds confusion to an already vague clinical area. PMID- 3339665 TI - Myocardial contusion: when does it have clinical significance? AB - A retrospective review of 53 patients with blunt chest trauma admitted to a monitored hospital bed demonstrated a single elderly patient with multiple injuries who developed dysrhythmias requiring treatment. The remainder of the relatively young group had no significant cardiac sequelae. We conclude that the routine use of expensive monitoring and extensive diagnostic tests in the young blunt chest trauma victim should be reconsidered. PMID- 3339667 TI - The Abbreviated Injury Scale, 1985 revision: a condensed chart for clinical use. AB - Refinements in injury scaling of blunt trauma and expansion to include penetrating injuries have resulted in the publication of the 1985 revision of the Abbreviated Injury Scale (AIS). To simplify use of this scale for Injury Severity Scoring in clinical practice, two 8 1/2" x 11" charts, which can be included in the patient record, have been developed from the AIS dictionary. Separate charts apply to blunt and penetrating trauma. Previous experience with a condensed AIS chart (CAIS) using the 1980 revision of the dictionary suggests that such edited revisions can result in accurate injury scaling in more than 95% of patients presenting to a Level I Trauma Center. The availability of such charts assists in calculation of the ISS soon after admission, which may prove to be a valuable teaching tool and useful in resource allocation, audit, and assessment for prospective payment. PMID- 3339666 TI - A comparison of Abbreviated Injury Scale 1980 and 1985 versions. AB - The 1980 and 1985 versions of the Abbreviated Injury Scale (AIS) are quantitatively and qualitatively compared based on experience gained during the recent coding of nearly 115,000 injuries from more than 33,000 seriously injured patients using both AIS versions. Quantitative comparisons are based on differences in AIS scores and Injury Severity Score (ISS) values which result under the two schemes. Qualitative comparisons concern the completeness and clinical usability of the two scales in a trauma center setting. PMID- 3339668 TI - Urban-rural location and the risk of dying in a pedestrian-vehicle collision. AB - Statewide data from two sources were used to compare the pedestrian-vehicle collision injury and fatality rates for urban and rural areas of Washington State from 1981 through 1983. Although the rates of pedestrian injuries are higher in urban areas, the pedestrian fatality rate in rural areas is higher for nearly all age groups, and at all posted speeds. Multiple logistic regression was carried out to measure the risk of dying once involved in a pedestrian-vehicle collision in rural areas compared to the risk for urban areas. This relative risk was seen to be elevated (RR = 2.3; 95% CI = 2.0-2.6) even after controlling for the effects of age and sex of the pedestrian, and posted speed of the vehicle. When explored further it was seen that a larger proportion of fatalities died out of the hospital and within the first hour after injury in rural areas than in urban areas. It is possible that Emergency Medical Services care is less rapidly available and that accessibility to trauma centers is more limited in rural areas. PMID- 3339669 TI - Proceedings of the 5th International Symposium on Wound Ballistics. Gothenburg, Sweden, June 11-14, 1985. PMID- 3339670 TI - The characteristics of the pressure waves generated in the soft target by impact and its contribution to indirect bone fractures. AB - When a high-velocity spherical fragment impacts a biological body, it will initiate strong pressure waves spreading throughout the body. A pressure wave, especially a shock wave with a steep front, generated by impact, may cause blood vessel injuries, viscera injuries, and indirect bone fractures. This paper reports research on pressure waves near the wound tracks, generated by spherical fragments, and calculates the zones of indirect bone fractures generated by pressure waves of impact. PMID- 3339671 TI - Experimental gunshot fractures. PMID- 3339672 TI - Predicted thoraco-abdominal response to complex blast waves. PMID- 3339673 TI - Intrathoracic pressure variations in an anthropomorphic dummy exposed to air blast, blunt impact, and missiles. AB - Experiments with an anthropomorphic dummy for blast research demonstrated that pressures recorded in the lung model of the dummy could be correlated to primary air blast effects on the lungs of experimental animals. The results presented here were obtained with a dummy of the type mentioned above, but with the lung model modified to improve geometric similarity to man. Blast experiments were performed in a shock tube, and impact experiments in a special impact machine. Experiments with nonpenetrating missiles were performed with small-caliber firearms and the dummy protected by body armor. Severity indices derived from the blast experiments were related to established criteria for primary lung injury in man. Impacts delivered in the impact machine and by nonpenetrating missiles are compared. Relationships between severity of impact based on experiments with animals and primary lung injury in man are discussed. PMID- 3339674 TI - Characteristics of cavities trailing different projectiles penetrating water. PMID- 3339675 TI - Computer modeling of thoracic response to blast. AB - Primary blast injury affects the gas-containing structures of the body. Damage to the lungs with resultant respiratory insufficiency and arterial embolization of air from alveolar pulmonary venous fistulae is the predominant cause of morbidity and mortality following high-level blast exposure. In an effort to generate a widely applicable damage-risk criterion for thoracic injury from blast we are developing a complex computer finite element model (FEM) of the thorax. Taking an engineering approach, a horizontal cross-section of the thorax is divided into small discrete units (finite elements) of homogeneous structure. The necessary physical properties (density, bulk modulus, etc.) are then determined for each element. Specifying the material constants and geometry of the elements, the computer can load the surface of the structure with some force-time function (blast pressure-time history) and calculate the resultant physical events such as displacement, compression, stress, strain, etc. Computer predictions of pressure wave phenomena in the lung parenchyma are compared with trans-bronchially measured pressures in blast-exposed animals. The model should prove useful in assessing the risk of blast injury in diverse overpressure environments and may give insight into pathophysiologic mechanisms and strategies for protection. PMID- 3339676 TI - Comparison of low- and high-velocity ballistic trauma to genitourinary organs. PMID- 3339677 TI - Some observations relating to behind-body armour blunt trauma effects caused by ballistic impact. AB - Live, anesthetised pigs were used to assess behind-armour blunt trauma effects. The thoraco-abdominal body region was covered with varying thicknesses of Kevlar fabric packets. This soft body armour was applied, either in direct contact with the thoracic wall of the animals, or with different plastic foam sheets, so called trauma packs, between the armour and the skin. The live animals were surgically evaluated, and then sacrificed. Blocks of soft soap were subjected to equal tests and the behind-armour indentations were measured. The results indicate that serious injury to the body armour-protected chest may be caused by the impact of nonpenetrating bullets and shotgun pellets. Severe pulmonary contusions and lacerations were found when the energy transferred through the body armour was estimated to be high. PMID- 3339678 TI - Cloth ballistic vest alters response to blast. AB - Ballistic wounds have been and will remain the principal cause of casualties in combat. Cloth ballistic vests (CBV) play an important role in limiting critical wounds from fragments and small-arms fire. There is an increased risk of primary blast injury on the modern battlefield. In a previous study, volunteers were exposed to short-duration blast waves of low peak pressure (18.6 +/- 0.8 kPa). Pressure measurements made in the distal esophagus as an estimate of intrathoracic pressure (ITP) were significantly higher (p less than 0.05) when the standard U.S. Army ballistic jacket was worn (8.7 +/- 1.2 kPa) than when fatigues alone were worn (7.4 +/- 0.7 kPa). In this study 58 sheep were exposed to nominal blast levels of 115, 230, 295, and 420 kPa peak pressure in groups of 12, 18, 16, and 12, respectively. Half of each group was fitted with a CBV. Lung weight index (LWI), lung weight expressed as a percentage of body weight, was used as a measure of blast injury. Use of the CBV was associated with a significant increase in LWI (p less than 0.05) which averaged 21% for the two middle exposure groups. At the 420 kPa level, two of six non-CBV animals died as opposed to five of six animals wearing the CBV. Intrathoracic pressure was generally higher in the CBV group. Likely mechanisms of injury enhancement include an increase in target surface area and an alteration of the effective loading function on the thorax. This information may be useful in the triage and treatment of casualties exposed to intense blast environments. PMID- 3339681 TI - Three-dimensional computer graphic modeling of ballistic injuries. AB - Multiple variables affect the tissue destruction caused by missiles, and the interaction of these variables is incompletely understood. The recently developed technology of computerized solid modeling now makes it possible to analyze these parameters in three dimensions. A technique for creating solid models of organic structures is described. The tissues within the boundaries thus defined are ascribed physical attributes by means of finite element analysis with data derived from empirical studies. An interactive user-friendly program is being developed combining this modeling with a probabilistic scheme (Monte Carlo simulation) to describe a variety of wounding scenarios. The data from these predictions will be compared with information from wound registries and the model refined until it can project consistently accurate patterns of injury. PMID- 3339679 TI - Readily available serum chemical markers fail to aid in diagnosis of blast injury. PMID- 3339680 TI - Twenty-one-year experience with land mine injuries. AB - Land mines produce devastating injuries which are usually fatal. In Guantanamo Bay, there have been no survivors from close range, functioning antipersonnel mines of the M-16 series. All 15 antipersonnel mine fatalities suffered extremity amputation. Seven of the 15 patients suffered immediately fatal head, neck, or truncal injuries (Type I injury). The three patients who underwent hospital resuscitation had extremity amputation but were spared major head, neck, or truncal injury. It is in this group of injured that potentially salvageable patients can be identified; for them aggressive rescue and resuscitation must be performed. Those with Type II injuries are the highest priority in any triage plan. In a mass casualty or combat casualty scenario, Type II patients, in particular those with high bilateral above-the-knee amputations, may be reassigned to an expectant treatment category so as to allow the main focus on more salvageable patients. The prehospital management plan emphasizes rapid assessment and triage of patients, use of tourniquets to control extremity hemorrhage, supplemental oxygen or endotracheal intubation if possible, neck immobilization, use of the extremity section of the pneumatic antishock garment if applicable, and rapid transport to a hospital. Hospital management of these patients emphasizes aggressive resuscitation, early endotracheal intubation, and rapid volume replacement with simultaneous balanced salt solution and blood. Operative debridement with broad-spectrum antibiotic coverage and tetanus prophylaxis is performed; wounds are managed in an open fashion and frequently examined at subsequent dates in the operating room. PMID- 3339682 TI - Gunshot wounds caused by modern firearms in the light of our investigations. AB - The experiment was carried out on 27 sheep with traumatic-haemorrhagic shock caused by a gunshot wound produced using high-velocity missiles from the HM16 rifle. Sixty minutes after injury treatment with blood-replacing fluids was started. In Group I Ringer's solution with sodium lactate pH 8.2 was infused, Group II received Ringer's solution with sodium lactate pH 6.5, and Group III was given Ringer's solution alone. Volume of the infused fluid exceeded threefold the volume of lost blood. During and after fluid replacement blood samples were drawn for biochemical investigations and haemodynamic disturbances were carefully observed. In conclusion, we can say that Ringer's solution filled the vascular bed and improved tissue perfusion, but it failed to correct metabolic and acid base equilibrium disturbances to such a degree and for as long a long time as did Ringer's solution with lactate. PMID- 3339683 TI - Intra-abdominal vascular injury secondary to penetrating trauma. AB - There were 85 patients in this series. The overall mortality was 17.6%. Gunshot wounds were responsible for 51 injuries, with a 21% mortality. There were three stabbings and three shotgun blasts, with a mortality of 10% and 33%, respectively. There were 127 intra-abdominal vascular injuries. The majority were to the SMA and its branches: 34. The highest mortality occurred with protal vein and combined aortic and vena caval injuries (80%). Fatalities averaged twice as many vascular injuries as survivors. There were 194 organ injuries. A liver injury predicted the highest mortality as did injuries to the spleen, lung, and pancreas. The presence of shock and the ability to rapidly control the source were the major predictors of survival. Fatalities averaged a Trauma Score of 7.5; survivors averaged a score of 14.0. There were 12 deaths which occurred intra operatively and three postoperatively, for a total of 15 deaths. Once the patients made their way from surgery, their survival was 96% assured. Early suspicion of an intra-abdominal vascular injury followed by rapid exposure and control of hemorrhage are the keys to successful management. PMID- 3339685 TI - A scanning fluorometer for imaging ischaemic areas in traumatized muscle. AB - The criteria used to evaluate the state of muscle surrounding a bullet wound are: a lack of contractility, a lack of capillary bleeding, and changes in colour and consistency. Muscle with all these properties may be assumed to be irreversibly damaged. However, the boundary between such tissue and tissue with potentially reversible levels of damage may not be clear cut. In general, oxygen lack due to blood vessel damage may be sufficient to cause irreversible damage or may result in a site of anaerobic infection. Such areas may occur at some distance from the missile track. Tissue responses to oxygen lack can be monitored by observing changes in intrinsic cellular fluorescence. The blue autofluorescence of intracellular pyridine nucleotides increases with anoxia, whereas the green autofluorescence of intracellular flavoprotein has been found to decrease with anoxia. We have developed a scanning fluorometer which rapidly provides an image of the distribution of anoxic areas in soft tissues. In experiments with anaesthetized rabbits, occlusion of the blood vessels to the gracilis muscle caused an increase in its pyridine nucleotide fluorescence and a decrease in its flavoprotein fluorescence. The changes were hastened by stimulation of the muscle to fatigue. Arterial infusion of colloidal carbon confirmed that adjacent muscles still had a blood flow. The apparatus has potential for the identification of hypoxic zones peripheral to the permanent wound cavity. Conversely, it may also help to indicate whether vascular repair after trauma of large blood vessels has led to improvement of the metabolic status of tissue being reperfused. PMID- 3339684 TI - Medical simulation for disaster casualty management training. AB - A required, role-intensive leadership simulation in emergency and disaster medicine management for fourth-year medical students is described, and the value of an extended role-playing experience discussed. The week-long (120 hours) simulation exercise is designed to provide an opportunity for Federal medical students to experience a realistic combat or disaster environment similar to environments in which they may be required to operate medical support systems. Students function in a variety of roles and have the opportunity to place into practice all emergency medical knowledge and skills acquired throughout medical school. As a prerequisite to the exercise, students successfully complete a 3 week didactic course in Operational and Emergency Medicine which includes Advanced Cardiac Life Support (ACLS) and Advanced Trauma Life Support (ATLS) Provider Courses. By means of disaster simulation they refine medical skills, leadership style, substantially improve clinical judgment, and deal with the complexities of problems associated with their future roles as medical officers. PMID- 3339686 TI - Central and peripheral nervous damage following high-energy missile wounds in the thigh. PMID- 3339687 TI - Remote cerebral effects on EEG in high-energy missile trauma. AB - Preliminary observations show that under certain circumstances high-energy missile trauma to soft tissue causes a transient depression of the EEG. Similar effects on the central nervous system elicited by the pressure and shock waves might be the cause of the acute behavioural and mental blockage reported in man by nonfatal wounds from missiles of this type. The mechanism behind the effects observed is not yet known, nor can the absence of EEG effects in some animals be explained at present. Further studies of the remote cerebral effects of high energy missile trauma should be carried out. PMID- 3339688 TI - A new model to determine the central nervous system reaction to peripheral trauma. AB - Monitoring the activity of the central nervous system with the 14C-2-deoxyglucose method of Sokoloff was utilized to explore the possibility to develop a model for the study of central nervous system reaction to peripheral trauma. Preliminary evidence indicates that the activation caused by tactile stimuli to one hindlimb nerve is that expected from earlier physiologic studies. However, an increase of stimulation intensity to recruit nociceptive (pain) fibers seems to abolish the changes, indicating that inhibitory systems have been activated. PMID- 3339689 TI - The wound profile: illustration of the missile-tissue interaction. AB - The wound profile was developed at the Letterman Army Institute of Research in order to measure the amount, type, and location of tissue disruption produced by a given projectile, and to present the data in a standardized, easy to understand picture. The entire missile path is captured in one or more 25 X 25 X 50 cm blocks of 10% ordnance gelatin at 4 degrees C. The penetration depth, projectile deformation and fragmentation pattern, yaw, and temporary cavity of the missile in living anesthetized swine muscle are reproduced by this gelatin. Measurements are taken from cut sections of the blocks after mapping of the fragmentation pattern with biplanar X-rays. These data are then reproduced on a life-sized wound profile which includes a scale to facilitate measurement of tissue disruption dimensions, a drawing of the loaded cartridge case before firing, the bullet weight and morphology before and after firing (and calculated percent of fragmentation), and the striking velocity. This technique allows us to determine the wounding character of the projectile without the need for elaborate and expensive high-speed cine and X-ray equipment, or the need for shooting live animals. The method improves our understanding of the wounding process and should lay the groundwork to assure more rational and effective treatment. PMID- 3339691 TI - Quantitative bacteriological study of the wound track. AB - Missile wounding was carried out to the hind legs of 46 mongrel dogs. The impact velocity was 730-1,570 m/s. The shot fragments were 0.44-1.03 gm in weight, 4.76 mm in diameter. The number of bacteria in devitalized muscle tissue, at 6, 12, and 24 hours after wounding, was studied by the usual bacteriologic methods. The studies showed that the number of aerobes in devitalized muscle was 10(3) 10(4)/gm tissue at 6 hr, 10(5) at 12 hr, and 10(5) at 24 hr after wounding. The number of anaerobes at 6 hours after wounding was 10(4)-10(5). The number of bacteria in the devitalized zone was greater than that in the healthy zone. Bacterial cultures were always positive if the specimens were taken immediately after injury. PMID- 3339690 TI - Effect of high-velocity missile injury on plasma cortisol concentration in dogs. AB - Plasma cortisol concentrations were measured in nine dogs after high-velocity missile injury induced by spherical steel bullets. All nine dogs sustained soft tissue wounds in the thighs without damage to large vessels, femur, or nerves. When the dogs were considered as one group the mean plasma cortisol concentration increased promptly 10 min after injury (p less than 0.05) and reached its peak at 1 hour and then decreased. The mean concentration at 6 hours after injury was still higher than that before injury (p less than 0.05). Even though the severities of the injuries varied rather much there was a significant difference (p less than 0.01) between the plasma cortisol concentrations at 1 hour of the two groups into which the dogs were divided according to the severity of their injuries. The changes of the plasma cortisol concentrations may be parallel with the extent of the injuries and there was a positive correlation with the dimensions of the entrance wounds. PMID- 3339692 TI - Effects of phospholipase C, a tissue thromboplastin inhibitor, on pulmonary microembolism after missile injury of the limb. AB - Tissue thromboplastin probably plays an important role in the development of post traumatic pulmonary microembolism. Infusion of purified human tissue thromboplastin in animals resulted in an intravascular coagulation and respiratory insufficiency. This could be inhibited by previous infusion of phospholipase C (PLC) from Bacillus cereus. We have studied the effects of PLC infusion on the course of post-traumatic pulmonary microembolism, induced by a high-energy (c. 700 J) missile trauma to the hind legs of pigs. The trauma resulted in a major muscular injury and an indirect femoral fracture. Untreated pigs developed intrapulmonary microemboli. The degree of microembolism in the lungs was measured quantitatively by external detection over the right lung of radiolabeled platelets and fibrin. Infusion of 80 micrograms PLC/kg/hour resulted in an accumulation of blood PLC associated with toxic reaction leading to increasing tachycardia and circulatory collapse after 10 hours. PLC infusion of 20 micrograms/kg/hour did not inhibit the pulmonary microembolism. A PLC-dose in between, viz. 40-50 micrograms/kg/hour, proved to efficiently inhibit most of the microembolism during the infusion period. Cessation of PLC infusion after 24 hours was accompanied by a later increase in pulmonary trapping of platelets and fibrin and decreases in paO2. Concomitantly there were opacities seen on chest X rays. The results show that tissue thromboplastin is an important etiologic factor in post-traumatic pulmonary microembolism and that inhibition with phospholipase C can be of value in the prophylaxis of the syndrome. PMID- 3339693 TI - Reactions of serum creatine kinase in early phase of spherical steel bullet injury. AB - On the basis of experimental study on 17 dogs, this paper reports on the variation of serum creatine kinase (SCK) with time in the early phase of wounding by spherical steel bullets at three different velocities and its relation with the kinetic energy absorbed by the tissue and with the amount of the excised necrotic tissue surrounding the wound tracks. The results showed that the energy absorbed by the tissue and the amount of the excised necrotic tissue surrounding the wound tracks increased with increasing velocity. Within a period of 6 hours after wounding the SCK activity increased correspondingly. PMID- 3339694 TI - An analysis of the wounding factors of four different shapes of fragments. AB - The wounding characteristics to a biological target of four typical shapes of fragments (square, triangular, cylindrical, and spherical) with masses of less than 1 gram and velocities between 460 and 1,500 m/s are studied in this paper. The following conclusions about the effects of the wounding factors, such as energy transfer, velocity, mass, and shape of fragment are presented: 1) For given target characteristics, the important wounding factors of fragments are impact velocity, mass, and shape, and of these velocity is the most important. 2) Besides direct effects, the fragment velocity has great influence on far reaching, indirect wounding effects. When velocity increases, it not only increases the size of direct wound, but also the rate of indirect bone fracture. 3) The rate of energy transfer is affected by fragment shape, and it is also a decreasing function of mass. 4) Under the same conditions there are differences in wounding effectiveness among the four fragment shapes, the triangular with a comparatively high wounding effectiveness, followed by the square, cylindrical, and spherical. The types of wound channels are also different, the cylindrical and spherical making a "through" type, the square and triangular making a "blind tube" type. PMID- 3339696 TI - Wounding properties of steel pellets with different velocities and quality on soft tissue of dogs. AB - The characteristics of the soft-tissue wounds of the hind legs of 155 dogs produced by stainless steel spheres with four different masses and at various impact velocities were observed. It was found that when the mass of the spheres was identical, the velocity became the main factor to determine the severity of the damage; when the mass of the spheres was different but their kinetic energy was similar, then a smaller but faster sphere produced more severe damage than a larger but slower one. Shallow but wide and severe wounds usually resulted. The rate of disability of extremities with such wounds was very high. These wounding properties of steel spheres have caused some new problems in the treatment of war injuries. PMID- 3339695 TI - Scale effects in ballistic wounding. PMID- 3339698 TI - Physical effects of the penetration of head simulants by steel spheres. PMID- 3339697 TI - The wounding characteristics of spherical steel fragments in live tissues. AB - This paper reports the wounding effectiveness tests of four kinds of spherical steel fragments, striking against live tissues at various velocities. The most pronounced wound characteristic for the spherical fragments was that the entrances were larger than the exits; the higher the striking velocity, the larger the size of the wound. The skin near the entrance tended to be torn away when the striking velocity was above 1,200 m/s. As a general rule, most exits appeared to be circular with a diameter slightly bigger than that of the fragment. Shapes of the wound channels were conic in general. The channel volumes were proportional to the striking velocities of the fragments; in the case of two spheres having the same striking energy, the small one would produce larger volume of wound channel and amount of debrided tissues. The energy release rate for smaller fragments was higher than that for larger ones. PMID- 3339699 TI - Predicting temporary cavity size from radial fissure measurements in ordnance gelatin. PMID- 3339700 TI - Wound-dynamic studies in Australia. AB - As part of the Australian programme of studies in wound ballistics, a facility has been developed at the Materials Research Laboratories, Melbourne, Victoria, in which the phenomena associated with the penetration of bullets through tissue simulants can be investigated. This paper outlines the development programme and describes a recent series of comparative firings of 7.62-mm and 5.56-mm ammunition into gelatin tissue simulant. PMID- 3339701 TI - Terminal behaviour of deforming bullets. AB - Some types of deforming bullets, including soft-point hunting ammunition and so called shotgun slugs, were fired against blocks of soft soap and against the muscular parts of the hind legs of live, anesthetised pigs. The deformation, breakup, and retardation of the bullets within the targets were recorded by means of a multi-flash X-ray setup. The extent of the soft-tissue damage was evaluated by means of debridement performed by a highly skilled surgeon. The excised tissue was then accurately weighed. The potential to transfer energy of these bullets was, as could be anticipated, extremely high, and the injuries caused were very large. The relations between bullet velocity, construction, deformation, breakup, and the resulting injuries are discussed. PMID- 3339702 TI - A reconsideration of the wounding mechanism of very high velocity projectiles- importance of projectile shape. AB - In 1976 a paper appeared which forecast "significant increases in velocities of projectiles from guns and fragments from warheads." It was postulated that the higher velocity projectiles would cause shallow wounds with wide tissue destruction on the surface--especially when striking velocity exceeded the speed of sound in tissue (about 1.5 km/sec). Other studies have not dealt with projectiles in this velocity range; the conclusions and assumptions stated in this 1976 paper have been quoted by others and accepted as fact. In a previous study, we shot blunt fragments into gelatin, but our findings did not support the proposed hypothesis that temporary cavity shape in tissue changes at velocities above the sonic speed. The temporary cavity becomes larger with increasing velocity but it does not become shallow unless the projectile fragments on impact. In the present study, we shot a series of blunt projectiles into animal tissue at velocities of 764 to 2,049 m/s. The stellate skin and muscle disruption splits from temporary cavity stretch we observed in this study are not apparent on entrance wounds from individual explosive device fragments in the living wounded. We suggest, therefore, that studies using blunt projectiles at striking velocities above 700 m/s are lacking in clinical relevance. We also compared wounds produced by pointed projectiles with those produced by blunt projectiles. The marked difference in wound morphology showed the fallacy of doing a study with blunt missiles and applying conclusions from that study to tissue disruption caused by all projectiles. PMID- 3339703 TI - Evaluation of the new type of military bullet and rifling. AB - The 5.56-mm caliber SS 109 projectile was fired from 7.7'' and 12'' twist rifles, respectively, into soap blocks and porcine thighs at 50-metre range using a standardized experimental setup. For comparison, the effects of the 5.56-mm M 193 bullet fired from the 7.7'' twist barrel and M-16 assault rifle were tested. The volume of residual cavity in soap, the shape and sizes of live tissue wounds, and the mass of surgically debrided devitalized tissue were measured. The effects of the two projectiles at 7.7'' twist were found similar in soap; the SS 109 produced more tissue damage than the M 193 missile. Using the 12" twist rifle, a significant increase in wounding capacity of SS 109 projectile was found. In conclusion, nonsignificant differences in local effects between the two projectiles using the 7.7'' twist rifles were found, and markedly increased effects of the SS 109--12'' system were ascribed to decreased essential stability and its earlier tumbling in penetrating a target. The soap as a live tissue simulant has proven its reliability in testing small-caliber arms. PMID- 3339704 TI - Internal deformation of the AK-74; a possible cause for its erratic path in tissue. AB - A series of 20 shots with the AK-74 Russian Assault Rifle, in which the entire course of the bullet was captured in gelatin, showed a change in direction of the bullet track approximating a right angle in every case. Bullets were recovered from the gelatin for ten consecutive shots of this series and examined roentgenographically. In all cases an internal deformation was discovered to have taken place: lead from the bullet's core flowed into the air space inside the bullet's tip. The roentgenograms also showed that this flow of lead resulted in an asymmetrical bullet in every case. We suggest this resulting bullet imbalance as a possible cause of the unusually marked curve in this bullet's path through tissue. PMID- 3339705 TI - Wound ballistics of Swedish 5.56-mm assault rifle AK 5. AB - The recently adopted Swedish standard 5.56-mm assault rifle Ak 5, with ammunition 5.56-mm sk ptr 5 stkprj, closely similar to the Belgian weapon FNC, with corresponding ammunition SS 109, was fired against blocks of soft soap and against the muscular parts of the hind legs of live, anesthetised pigs. The behaviour and retardation of the bullets within the targets were recorded by means of a stereo, multiflash X-ray setup. The extent of the soft-tissue damage was evaluated in sections by means of debridement performed by a highly skilled surgeon. The excised tissue was then accurately weighed. The energy transfer characteristics and the wounding potential of the weapon are discussed. PMID- 3339706 TI - An estimation of the physical characteristics of wounds inflicted by spherical fragments. AB - Based on test results of projecting four different types of spherical fragments, diameters of which were 3.175 mm, 4.763 mm, 5.56 mm, and 6.35 mm, respectively, into the biological soft tissues and the soap blocks used as simulants, an estimation of the physical characteristics of wounds inflicted by spherical fragments was established in this paper. With impact velocities in the range of 450-1,500 m/s, all four types of spherical fragments showed little variation in drag coefficients for each medium. Some specific wound characteristics such as amount of debrided tissue, volume of the wound channel, etc., can be predicted as functions of energy transfer for spherical fragments of less than 1 gram. PMID- 3339707 TI - Early pathomorphologic characteristics of the wound track caused by fragments. AB - Soft-tissue wounds were inflicted on the upper parts of both hind legs of dogs by fragments which were shot with a smooth-bore testing rifle. Three impact velocities were used: "high" (1,500 m/s, six dogs), "middle" (1,000 m/s, eight dogs) and "low" (700 m/s, seven dogs). Debridement and gross examination were carried out 6 hours after wounding. The main conclusions were as follows: 1) Grossly, most of the wound tracks were blind. The primary wound track in the "high"-velocity group looked like a funnel in shape. The wound cavity close to the entrance had the largest diameter. 2) The severity of the tissue damage depended on the impact velocity. The higher the velocity, the larger were the wound cavities, the more tissues damaged, and the wider was the area of tissue damage around the cavity. 3) Based on the gross, light microscopy (LM), and electron microscopy (EM) observations it was found that one of the predominant characteristics of the tissue damage caused by fragments was the irregularity or unevenness. This was especially true in the case of the "high"-velocity group. The distribution of tissue damage seemed to be "jumping" or "mosaic." This probably resulted from the irregularity of the energy delivery from fragments with high velocity and low mass. 4) The differences in morphologic characteristics between wound tracks caused by bullets and those by fragments are discussed. PMID- 3339708 TI - Pressure variation in temporary cavities trailing three different projectiles penetrating water and gelatin. PMID- 3339710 TI - Morphopathologic observations on high-velocity steel bullet wounds at various intervals after wounding. AB - Soft-tissue wounds of both hind legs in 15 dogs were inflicted by spherical steel bullets. Histologic and ultrastructural changes were observed in the contusion zone and the concussion zone at 6, 12, and 24 hr after wounding. Histologically, it was shown that at 6 hr after wounding, there were degeneration and necrosis of myofibers and interstitial hemorrhage and edema in the contusion zone, while some fibers still appeared to have normal structure in the outer layers. In the inner layers of the concussion zone close to the entrance, there was focal necrosis of myofibers. Histologic changes at 12 and 24 hr after wounding were similar to those at 6 hr but there were more inflammatory reactions. A considerable number of ultrastructural changes were seen in the contusion zone at 6 hr after wounding, such as loss of sarcomeres, vacuolization and pyknosis of mitochondria, swelling of sarcoplasmic reticulum, irregular arrangement of Z-lines, breaking of some capillary endothelial cells, etc. However, in the concussion zone, the changes were much less than those above mentioned, although karyons and karyomeres of some monocytes appeared to be gathering to the side of cytoblast. On the whole, the ultrastructural changes were not so severe at 12 and 24 hr as those at 6 hr after wounding. Also, the characteristic features of the wound caused by high-velocity steel bullets were not similar to those caused by 5.56-mm high-velocity missiles. The severity of damage at the entrance of wound track caused by steel bullet was more marked than that at the exit. PMID- 3339709 TI - Wounding effects of small fragments of different shapes at different velocities on soft tissues of dogs. AB - The wounding effects of small fragments of the same weight (0.44 gm) but different shapes and at different impact velocities (708-1,560 m/s) on the soft tissues of the hind legs of 156 dogs were studied. The experiments showed that velocity was the major factor in causing wounds. For fragments of the same shape, the energy transmission, volume of wound cavity, sectional areas at entrance and exit, and amount of tissue that had to be excised increased rapidly with increasing velocity. In particular, as the velocity reached about 1,500 m/s, a shallow and wide wound tract was liable to occur, peripheral tissue lesion was relatively apparent, even extended to the whole leg, and the rate of occurrence of bone fracture was high. The wounding effect of the shape of the fragment closely related to its sectional specific weight (W) and drag coefficient (CD). Given the weight of the projectile and the density and thickness of the tissue, the energy transmission (delta E) was directly proportional to the square of the velocity and to the drag coefficient, and inversely proportional to the sectional specific weight of the fragment. Therefore, under certain conditions, reducing the sectional specific weight often increased the drag coefficient, in favour of causing a wound. In this experiment, the extent of wounds caused by the triangular, the square, and the cylindrical, and the spherical fragments decreased in that order, in agreement with their values of sectional specific weight and drag coefficient. PMID- 3339711 TI - A model for the comparison of pharmacologic agents influencing gallbladder contraction. AB - Investigations on pharmacologic effects on gallbladder contraction must take into consideration the spontaneous motility of the gallbladder. In 20 healthy subjects, we measured the area of the gallbladder sonographically over 10 h at hourly intervals. The spontaneous motility expressed as a coefficient of variation varied between 1.6 and 13% (mean value, 6.3%). Afterwards, we checked the cholecystokinetic action of ceruletide and fatty meal in eight subjects. Here, an alteration of the area by four times the previously found coefficient of variation was defined as significant. A significant contraction occurred earlier after ceruletide administration than after a fatty meal (10 min as compared to 20 min). This lasted longer (40 min. vs. 25 min) and led to a very much more marked reduction in area (69% as compared to 53%). These differences were significant on a 5% level. The end of the contraction did not differ (50 min as compared to 45 min). We conclude that drugs which affect gallbladder contraction can be compared with consideration of spontaneous motility. PMID- 3339713 TI - Characterization of vaccinia virus growth factor biosynthetic pathway with an antipeptide antiserum. AB - A synthetic peptide derived from vaccinia virus growth factor (VGF) was used as an immunogen to prepare antiserum able to immunoprecipitate native VGF from both vaccinia virus-infected cell lysate and cell-free medium. Pulse-chase, tunicamycin treatment, and carbohydrate trimming experiments revealed that VGF is synthesized as a 19-kilodalton (kDa) precursor which is rapidly modified to a high-mannose-type 22-kDa protein. This cell-associated form is further processed into a 25-kDa polypeptide which, after proteolytic cleavage, releases the mature VGF into the medium as a 22-kDa glycoprotein. PMID- 3339712 TI - Delineation of the viral products of recombination in vaccinia virus-infected cells. AB - Plasmids containing the vaccinia virus thymidine kinase gene, its flanking DNA sequences, and the Escherichia coli beta-galactosidase gene were used in conjunction with a thymidine kinase-deficient virus to examine the viral products of recombination. Progeny derived from single-crossover events could be distinguished from those generated by gene conversion or double-crossover events when the beta-galactosidase gene was separated from the thymidine kinase gene by the flanking sequences. Using methotrexate to select for recombinant virus and a chromogenic indicator to detect beta-galactosidase, the generation of viral recombinants was measured over a 48-h period. Recombinant progeny were first observed at 12 h and increased to a maximum of 2.5% at 48 h. Single-crossover products, as determined by beta-galactosidase expression, reached a maximum of 57% of the recombinant population at 24 h and thereafter declined. DNA hybridization analysis was used to examine genomic structures of the progeny of the initial viral plaques, plaques purified three times, and those subject to a 10(4)-fold amplification. These analyses confirmed that single-crossover events within either the 5'- or 3'-homologous flanking sequences generated unstable recombinant structures. These structures were shown to contain a single copy of the intact thymidine kinase gene within the corresponding copy of the duplicated thymidine kinase flanking sequences, separated by the beta-galactosidase gene and plasmid DNA. Significantly, these duplicated structures could undergo further recombination to produce repeats of either the intact or the deleted thymidine kinase sequences. These intermediate structures ultimately degenerated to produce either the parental thymidine kinase-deleted or the wild-type genome. The wild type genome was also shown to be generated directly by gene conversion or double crossover events. PMID- 3339714 TI - Rift Valley fever virus M segment: use of recombinant vaccinia viruses to study Phlebovirus gene expression. AB - Recombinant vaccinia viruses were constructed and used in conjunction with site specific antisera to study the coding capacity and detailed expression strategy of the M segment of the Phlebovirus Rift Valley fever virus (RVFV). The M segment could be completely and faithfully expressed in recombinant RVFV-vaccinia virus infected cells, the gene products apparently being correctly processed and modified in the absence of the RVFV L and S genomic segments. The proteins encoded by the RVFV M segment included, in addition to the viral glycoproteins G2 and G1, two previously uncharacterized polypeptides of 78 and 14 kilodaltons (kDa). By manipulation of RVFV sequences present in the recombinant vaccinia viruses and use of specific antibody reagents, it was found that the 78-kDa protein initiated at the first initiation codon of the open reading frame and encompassed the entire preglycoprotein and glycoprotein G2 coding sequences. The 14-kDa protein appeared to begin from the second in-phase ATG and was composed of only the preglycoprotein sequences. Both viral glycoproteins G2 and G1 could be synthesized and correctly processed in the absence of the 78- and 14-kDa proteins, as well as a large portion of the preglycoprotein sequences. However, the hydrophobic amino acid sequence immediately preceding the mature glycoprotein coding sequences was required for authentic glycoprotein production. The M segment expression strategy involving aspects of translational initiation and protein processing are discussed. The functional roles of the 78- and 14-kDa proteins remain unclear. PMID- 3339715 TI - The NS-1 polypeptide of minute virus of mice is covalently attached to the 5' termini of duplex replicative-form DNA and progeny single strands. AB - When A9 cells are infected with minute virus of mice, a small proportion of the virally coded NS-1 polypeptide becomes covalently attached to newly synthesized viral DNA. Antisera directed against NS-1 will specifically precipitate two forms of monomer duplex replicative-form DNA, multimeric duplex intermediates and progeny single strands, and restriction analysis of the duplex forms in these precipitates reveals that NS-1 is exclusively associated with extended-form conformers of the genomic termini. Pulse-labeled viral DNA, harvested at various times in a highly synchronized infection, can be almost quantitatively precipitated with any one of a series of antisera directed against different protein domains distributed throughout the NS-1 molecule but not with antibodies directed against other viral proteins. In each case the interaction with NS-1 can be shown to involve both termini of duplex DNA and single-strand forms, suggesting that in each case a full-length (83-kilodalton) copy of NS-1 is present. Precipitation of the replicating viral DNA with an antibody directed against a synthetic 16-amino-acid peptide containing the sequence at the extreme carboxy terminus of NS-1 can be quantitatively and specifically inhibited with the immunizing peptide in its unconjugated form, showing that the antibodies responsible for precipitating viral DNA are directed against the NS-1 sequence itself and not against a trace contaminant. Exonuclease digestion studies show that the association effectively blocks the 5' ends of the DNA molecules. Very little (less than 0.1%) of the newly synthesized [35S]methionine-labeled NS-1 made in highly synchronized cells during a 15-min pulse early in infection (6.25 to 6.5 h into the S phase) becomes associated with viral DNA immediately. However, pulse-chase experiments show that later in infection (10 to 13 h into the S phase), when viral DNA replication is reaching its peak, a few percent of the molecules in these preexisting pools of NS-1 do become covalently attached to the newly replicated DNA. Isolated viral DNA-protein complexes labeled with [35S]methionine in this way can be obtained by fractionation of the immunoprecipitated complexes on Sepharose CL4B in sodium dodecyl sulfate. Digestion of the purified complexes with nuclease releases an 83-kilodalton molecule which exactly comigrates with authentic NS-1 in sodium dodecyl sulfate polyacrylamide gels. PMID- 3339716 TI - Deletion of the vaccinia virus growth factor gene reduces virus virulence. AB - The vaccinia virus growth factor (VGF) gene encodes a polypeptide with amino acid sequence homology to epidermal growth factor (EGF) and transforming growth factor alpha and is present twice, once at each end of the virus genome within the inverted terminal repetition. Recombination procedures were used to replace more than half of both VGF genes with a beta-galactosidase cassette which served as a color indicator for isolating an unconditionally viable VGF- mutant. The VGF- mutant genotype and phenotype were confirmed by Southern blot analysis and assays for functional growth factor. The plaque-forming efficiencies of VGF- and wild type (WT) viruses were similar in a variety of cell types containing low or high densities of EGF receptors, suggesting a lack of a specific requirement for either VGF or the EGF receptor in the initiation of virus infection. The yield of VGF- virus was similar to that of WT virus in growing BS-C-1 and Swiss 3T3 cells, but lower in resting Swiss 3T3 cells. The greatest differences between VGF- and WT virus occurred in vivo: higher doses of VGF- virus than WT virus were required for intracranial lethality in mice and for production of skin lesions in rabbits. Thus, expression of the VGF gene is important to the virulence of vaccinia virus. PMID- 3339717 TI - Processing the nonstructural polyproteins of Sindbis virus: study of the kinetics in vivo by using monospecific antibodies. AB - Plasmids were constructed which contained a large portion of each of the four nonstructural genes of Sindbis virus fused to the N-terminal two-thirds of the trpE gene of Escherichia coli. The large quantity of fusion protein induced from cells containing these plasmids was subsequently used as an antigen to generate polyclonal antisera in rabbits. Each antiserum was specific for the corresponding nonstructural protein and allowed ready identification of each nonstructural protein and of precursors containing the sequences of two or more nonstructural proteins. These antisera were used to determine the stability of the mature nonstructural proteins and to examine the kinetics of processing of the nonstructural proteins from their respective precursors in vivo. Pulse-chase experiments showed that the precursor P123 is cleaved with a half-life of approximately 19 min to produce P12 and nsP3; P12 is then cleaved with a half life of approximately 9 min to produce nsP1 and nsP2. Thus, although the rate of cleavage between nsP1 and nsP2 is faster than that between nsP2 and nsP3, the latter cleavage must occur first and is therefore the rate-limiting step. The rate at which P34 is chased suggests that the cleavage between nsP3 and nsP4 is the last to occur; however the regulation of nsP4 function in Sindbis virus infected cells may be even more complex than was previously thought. The products nsP1 and nsP2 (and nsP4) are relatively stable; nsP3, however, is unstable, with a half-life of about 1 h, and appears to be modified to produce heterodisperse, higher-molecular-mass forms. In general, the processing schemes used by Sindbis virus and Semliki Forest virus appear very similar, the major difference being that most nsP3 in Sindbis virus results from termination at an opal condon, whereas in Semliki Forest virus cleavage of the P34 precursor is required. PMID- 3339719 TI - Percutaneous lithotripsy in morbid obesity. AB - Percutaneous lithotripsy is an established, safe, effective method for the management of renal calculi. Obesity long has been associated with increased surgical morbidity and may eliminate a patient from shock wave treatment. We compared 44 obese patients to 226 nonobese patients undergoing percutaneous stone management. Stone number, location and total stone burden were comparable in the obese and nonobese groups. There was no significant difference between the groups in hospital time, operative time, fragment rate, access success rate or morbidity. Percutaneous procedures offer successful alternatives with low morbidity for patients with renal calculous disease. PMID- 3339718 TI - Alkali action on the urinary crystallization of calcium salts: contrasting responses to sodium citrate and potassium citrate. AB - Alkali therapy is used commonly to prevent recurrent stone formation in patients with distal renal tubular acidosis. We compared the effects of potassium citrate to those of sodium citrate in 6 well defined cases of incomplete distal renal tubular acidosis. The patients were studied during a control phase, during potassium citrate treatment (80 mEq. per day) and during sodium citrate treatment (80 mEq. per day) chosen in random order. Potassium citrate caused a decrease in urinary calcium and a significant increase in urinary citrate that resulted in a significant decrease in the urinary saturation of calcium oxalate. It did not alter the saturation of brushite and sodium urate. However, while sodium citrate also was able to increase the urinary citrate level, there was no decrease in the urinary calcium (owing to the increased sodium load). Thus, the urinary saturation of calcium oxalate did not decrease as much as with potassium citrate and the saturation of brushite increased significantly. Moreover, the urinary saturation of sodium urate increased significantly owing to the enhanced sodium excretion. The results suggest that potassium citrate therapy may retard the crystallization of calcium oxalate and may not cause calcium phosphate crystallization. In contrast, sodium citrate may have no effect or it sometimes may accentuate the crystallization of calcium salts. Thus, our study supports the potential clinical advantage of potassium citrate therapy over sodium alkali treatment in patients with incomplete distal renal tubular acidosis and recurrent calcium nephrolithiasis. PMID- 3339721 TI - Antitumor effects of human lymphoblastoid interferon on advanced renal cell carcinoma. AB - Human lymphoblastoid interferon alpha was administered intramuscularly at a dose of 3 times 10(6) units per day to 25 patients with advanced renal cell carcinoma. Six patients (24.0 per cent) showed objective responses, including 2 with complete regression of tumors. Nine patients (37.5 per cent) showed disease stabilization, while the disease progressed in 9 others (37.5 per cent). All tumor responses (2 complete, 4 partial and 2 mixed responses) were seen in lung, skin and liver metastases in patients whose primary tumors had been removed. Mean time to response was 87 +/- 74 days (range 28 to 240 days) and mean duration of response was 6.5 +/- 6.4 months (range 1 to greater than 20 months). Human lymphoblastoid interferon alpha was a potential active antitumor agent in patients with advanced renal cell carcinoma. PMID- 3339720 TI - Spontaneous subcapsular renal hematoma: diagnosis and management. AB - Spontaneous subcapsular or perinephric hematoma in the absence of anticoagulation, arteritis or trauma is most likely due to an underlying renal tumor. Eight such patients recently have been evaluated and after nephrectomy 5 had small tumors undetectable by imaging techniques, including computerized tomography or angiography. In 1 patient a tumor was demonstrated preoperatively by angiography and in only 2 was a tumor not found. In the absence of an apparent etiology, patients with spontaneous renal bleeding and a normal contralateral kidney should undergo radical nephrectomy because of the extremely high incidence of small undetectable occult tumors, often less than 2 cm. in size. PMID- 3339722 TI - Microexplosion cystolithotripsy in 105 cases. AB - We treated 105 consecutive patients with bladder calculi by microexplosion lithotripsy, with a success rate of 100 per cent. The weight of the removed calculi averaged 18 gm., with a range of 2 to 305 gm. For the procedure spinal anesthesia was used in 78 patients, while general anesthesia was used in 24. Minor extraperitoneal bladder perforation occurred only once and it resolved spontaneously several days later. Presently, we consider microexplosion lithotripsy to be the treatment of first choice for bladder calculi. PMID- 3339723 TI - Cancer detection by quantitative fluorescence image analysis. AB - Quantitative fluorescence image analysis is a rapidly evolving biophysical cytochemical technology with the potential for multiple clinical and basic research applications. We report the application of this technique for bladder cancer detection and discuss its potential usefulness as an adjunct to methods used currently by urologists for the diagnosis and management of bladder cancer. Quantitative fluorescence image analysis is a cytological method that incorporates 2 diagnostic techniques, quantitation of nuclear deoxyribonucleic acid and morphometric analysis, in a single semiautomated system to facilitate the identification of rare events, that is individual cancer cells. When compared to routine cytopathology for detection of bladder cancer in symptomatic patients, quantitative fluorescence image analysis demonstrated greater sensitivity (76 versus 33 per cent) for the detection of low grade transitional cell carcinoma. The specificity of quantitative fluorescence image analysis in a small control group was 94 per cent and with the manual method for quantitation of absolute nuclear fluorescence intensity in the screening of high risk asymptomatic subjects the specificity was 96.7 per cent. The more familiar flow cytometry is another fluorescence technique for measurement of nuclear deoxyribonucleic acid. However, rather than identifying individual cancer cells, flow cytometry identifies cellular pattern distributions, that is the ratio of normal to abnormal cells. Numerous studies by others have shown that flow cytometry is a sensitive method to monitor patients with diagnosed urological disease. Based upon results in separate quantitative fluorescence image analysis and flow cytometry studies, it appears that these 2 fluorescence techniques may be complementary tools for urological screening, diagnosis and management, and that they also may be useful separately or in combination to elucidate the oncogenic process, determine the biological potential of tumors and monitor the results of chemopreventive, immunological and chemotherapeutic regimens. To our knowledge there has been no study in which quantitative fluorescence image analysis and flow cytometry were compared directly to assess the relative strengths and weaknesses for urinary tract cytology. Such a study could provide important information for urologists. PMID- 3339724 TI - Flow cytometry deoxyribonucleic acid determinations and cytology of bladder washings: practical experience. AB - Flow cytometry deoxyribonucleic acid measurements of bladder washings, routine bladder irrigation cytology and cystoscopic results were compared in a prospective fashion during 33 months of clinical urology practice. Of the 204 patients (286 specimens) studied 74 had bladder tumors or a history of bladder tumors and 130 had other genitourinary pathological conditions, including hematuria, cystitis, benign prostatic hypertrophy or prostatic carcinoma. Flow cytometry and cytology agreed with the cystoscopic findings in 93 per cent of the cases, whereas flow cytometry agreed with cytology in 84.6 per cent. When combined, flow cytometry and cytology were negative in only 1 case when several papillomas or grade I papillary carcinomas were present on cystoscopy, yielding a diagnostic accuracy of 99 per cent. The false negative rates for flow cytometry and cytology were 4.3 and 5.2 per cent, respectively, with false positive rates of 4.2 and 3.1 per cent, respectively. As expected the specimens that were missed by cytology were low grade tumors and those missed by flow cytometry were usually ulcerated invasive tumors. We believe that flow cytometry is a valuable adjunct to cytology and cystoscopy in the diagnosis, management and followup of patients with known or suspected bladder cancer. In addition, criteria for the diagnosis of cancer are changed such that specimens with a deoxyribonucleic acid tail and a large amount of hyperdiploid cells without a distinct stem line are considered suspicious and indicative of bladder pathology but they are not synonymous with the presence of carcinoma. PMID- 3339726 TI - Natural history and treatment of low and high risk superficial bladder tumors. AB - Since 1979 a prospective randomized trial was done to examine the efficacy of intravesical doxorubicin as prophylaxis against recurrence. After complete transurethral resection of the tumor, patients were divided into 3 groups at random: group 1-no further treatment after transurethral resection, group 2 doxorubicin twice weekly for 6 weeks and group 3-doxorubicin for 1 year. A total of 268 patients entered the study. Neither frequency of recurrences, tumor progression nor survival rate was improved significantly by the adjuvant treatment, so that only a limited number of patients will profit by instillation therapy. Analysis of previously reported data suggests that patients with superficial bladder tumors can be stratified into groups with appreciable differences in risk of progression. With regard to these results a differentiated use of a "wait and see" adjuvant intravesical therapy and more aggressive treatment after transurethral resection of superficial bladder tumors seems to be indicated rather than a general practice of chemoprophylaxis. PMID- 3339725 TI - The predictive value of flow cytometric information in the clinical management of stage O (Ta) bladder cancer. AB - Two blind retrospective flow cytometric studies were performed on archival stage O (Ta) papillary grades 1 to 2 transitional cell carcinomas of the bladder to learn whether deoxyribonucleic acid histogram patterns predict disease recurrence and progression. All patients with aneuploid histograms as predicted experienced recurrent disease. In 20 of 28 cases of recurrent disease the ploidy pattern changed during recurrence. Because of this finding we predicted disease progression if 2 or more histograms in the sequence were aneuploid. Two-thirds (8 of 12) of those having more than 1 aneuploid tumor incident experienced invasion, while only approximately a third (6 of 16) lacking repetitive aneuploidy had invasion. Furthermore, of the patients with 2 aneuploid lesions half had progression within 1 year and two-thirds within 2 years after the second aneuploid lesion. Therefore, it appears that in this disease deoxyribonucleic acid histograms can provide prognostic information beyond that obtained from tumor grade and stage. PMID- 3339727 TI - Superficial transitional cell carcinoma of the bladder associated with mucosal involvement of the prostatic urethra: results of treatment with intravesical bacillus Calmette-Guerin. AB - Intravesical Pasteur strain bacillus Calmette-Guerin was used to treat 8 patients with mucosal transitional cell carcinoma of the prostatic urethra associated with superficial transitional cell carcinoma of the bladder. Complete initial response in the prostatic urethra was obtained in 7 of the 8 patients. Two patients had progression of disease during intravesical bacillus Calmette-Guerin therapy (1 in the prostate and 1 in the bladder) and they received further surgical therapy. Of the 6 complete responders 1 patient had invasive ureteral, vesical and prostatic tumor 15 months after bacillus Calmette-Guerin therapy, and he underwent nephroureterectomy and cystoprostatourethrectomy. Two patients required additional transurethral therapy for recurrent superficial tumors in the bladder but they have shown no evidence of recurrence in the prostatic urethra. Three patients have remained free of disease at 8 to 36 months. Before radical cystoprostatourethrectomy and urinary diversion are recommended, our study supports a course of bacillus Calmette-Guerin therapy as initial treatment for patients with superficial transitional cell carcinoma of the bladder associated with mucosal involvement of the prostatic urethra. PMID- 3339728 TI - Primary squamous cell carcinoma of the male urethra: nuclear deoxyribonucleic acid ploidy studied by flow cytometry. AB - Flow cytometry analysis was performed on 30 primary male urethral squamous cell carcinoma specimens. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Bulbomembranous urethral tumors had a higher incidence of abnormal deoxyribonucleic acid ploidy patterns than penile urethral tumors (69 and 29 per cent, respectively). Of the tumors exhibiting a deoxyribonucleic acid diploid pattern and an abnormal (deoxyribonucleic acid tetraploid or aneuploid) histogram 18 and 93 per cent, respectively, showed tumor progression (p less than 0.001). None (0 per cent) of the low grade (grade 1 or 2) tumors with a deoxyribonucleic acid diploid pattern developed local recurrence or distant metastases, whereas 90 per cent of the low grade tumors with an abnormal deoxyribonucleic acid pattern progressed (p less than 0.002). Patients with tumors exhibiting deoxyribonucleic acid diploid ploidy had 5 and 10-year rates free of disease of 85 per cent. In contrast, patients with tumors with abnormal deoxyribonucleic acid ploidy patterns had 5 and 10-year rates of 20 and 0 per cent, respectively (p less than 0.001). Determination of deoxyribonucleic acid ploidy pattern by flow cytometry provides important prognostic information for male patients with primary squamous cell carcinoma of the urethra. PMID- 3339730 TI - Testicular seminoma: the M. D. Anderson experience. An analysis of pathological and patient characteristics, and treatment recommendations. AB - We treated 240 patients with testicular seminoma at our institution between January 1960 and December 1982. The over-all 5-year survival free of disease for these patients regardless of stage was 93.6 per cent. The 165 patients (69 per cent) with stage I disease had a 95.5 per cent 5-year survival free of disease that remained constant at 20 years. Stage II cancer was diagnosed clinically in 62 patients (26 per cent), while 13 (5 per cent) presented with more advanced (stages III and IV) disease. The 5-year survival rate free of disease for all patients with stage II cancer was 85 per cent. There were 14 pathological and patient characteristics analyzed, 4 of which were statistically significant. All but 1 of these factors (spermatic cord invasion) was related to tumor volume (stage, palpable mass and hydronephrosis). Based on the data of this retrospective review, the Canadian experience without prophylactic mediastinal irradiation and the development of effective chemotherapy, we recommend radiation therapy without prophylactic mediastinal irradiation for patients with stage I or IIA disease and chemotherapy for patients with stage IIB, III or IV disease. In an attempt to improve our results in the latter patients we recently instituted adjunctive radiotherapy for those with a persistent radiographic mass. Our current guidelines for the staging evaluation and followup of patients with this neoplasm also are discussed. PMID- 3339729 TI - Detection of carcinoma in the post-cystectomy urethral remnant by flow cytometric analysis. AB - Following radical cystoprostatectomy for bladder cancer patients must be monitored for carcinoma of the urethral remnant. Cytological examination of urethral washings has proved to be a useful alternative to urethroscopy and urethrography. Urethral irrigation specimens also can be evaluated objectively by flow cytometry. In each of 4 patients in whom carcinoma developed in the urethral remnant analysis of urethral irrigation by flow cytometry was positive and comparable to results of urethral irrigation cytology. Flow cytometry is an objective and apparently reliable diagnostic test for malignancy in the urethral remnant. PMID- 3339732 TI - Stirrups to minimize complications of prolonged dorsal lithotomy positioning. AB - We evaluated the incidence of postoperative complications associated with positioning in 150 patients who underwent radical retropubic prostatectomy or radical cystectomy with urinary diversion in the modified dorsal lithotomy position. English stirrups were used in the first 75 patients, whereas a new type of stirrup modified from a Krauss arm support was used in the second 75 patients. Use of the new stirrups in the second group significantly decreased the postoperative morbidity associated with the dorsal lithotomy position from 13.3 to 2.6 per cent (p less than 0.05). PMID- 3339731 TI - Specific gravity test strips used in monitoring urine concentrations of urolithiasis patients. AB - Current therapy for urolithiasis patients includes instructions to increase water intake and 24-hour urine output. Previous studies have measured changes in the 24 hour urine volume to evaluate the efficacy of fluid therapy in each patient. We used paper test strips to monitor urine pH and specific gravity in 22 of our stone clinic patients: 10 were instructed to increase water intake just before the study (group 1) and 12 were not so instructed (group 2). Mean specific gravities of 1.0222 (1.0238 corrected for pH) for group 1 and 1.0197 (1.0220 corrected for pH) for group 2 did not differ significantly. Urine specific gravities also were compared for 3 intervals: 1 to 9 a.m., 9 a.m. to 5 p.m. and 5 p.m. to 1 a.m. Of the 22 patients 10 (3 from group 1 and 7 from group 2) had significant diurnal variations in the urine specific gravities, corrected and uncorrected, among these 3 periods. In addition, both groups had a significantly higher mean specific gravity from 1 to 9 a.m. (1.0234 uncorrected and 1.0248 corrected) than from 9 a.m. to 5 p.m. (1.0194 uncorrected and 1.0218 corrected). The 5 p.m. to 1 a.m. (mean of 1.0220 uncorrected and 1.0239 corrected) specific gravity did not differ significantly in either group. If 1.015 is the highest acceptable specific gravity of urine in stone patients, the findings suggest inadequate dilution of urine in these patients, whether or not they were instructed to increase water intake. Also, the significant diurnal variation in urine specific gravity would allow a nighttime triggering event at these hours of higher urine concentration. PMID- 3339733 TI - The surgical management of megaureters in duplex systems: the efficacy of ureteral tapering and common sheath reimplantation. AB - We describe 6 children with renal duplication associated with megaureter(s) who underwent ureteral tapering and common sheath reimplantation. Of the patients 4 had complete duplication with reflux into 1 or both ureters and 2 had incomplete duplication with a short distal segment that was obstructed at the ureterovesical junction. All obstructed or refluxing ureteral segments were dilated to a degree that tapering was required at the time of common sheath reimplantation. Megaureter repair in the presence of a duplicate collecting system proved to be safe and reliable. PMID- 3339734 TI - Collateral urethral duplication in the frontal plane: a spectrum of cases. AB - Collateral urethral duplication in the frontal plane is a rare anomaly. We report 3 cases of this variant of urethral duplication and review the literature. Double stream was the most frequent complaint and associated midline defects were common. Management, including a unique method of surgical intervention, is discussed. PMID- 3339735 TI - Testicular histology in fetuses with the prune belly syndrome and posterior urethral valves. AB - Intra-abdominal cryptorchidism and infertility are universal features of the prune belly syndrome but they usually are not seen with posterior urethral valves. To understand further the differences between these patients we reviewed testicular histology in 5 fetuses from each of 3 groups: prune belly syndrome, posterior urethral valves and normals. Spermatogonia were noted in all but the numbers were significantly reduced in those with the prune belly syndrome and posterior urethral valves compared to normals: 8.6 and 13.4 versus 31.2 per 10 high power fields, respectively. The fetuses with the prune belly syndrome also had marked Leydig cell hyperplasia in contrast to the other groups. These findings suggest that the testicular pathological condition in patients with the prune belly syndrome is caused by more than mechanical cryptorchidism. PMID- 3339736 TI - Hereditary xanthinuria in 2 Pakistani sisters: asymptomatic in one with beta thalassemia but causing xanthine stone, obstructive uropathy and hypertension in the other. AB - We describe a 3-year-old Pakistani girl who presented with recurrent urinary infections. She had a nonfunctioning hydronephrotic right kidney and hypertension. At operation a calculus was impacted in the right ureter with dilatation of the pelviocaliceal system. Nephrectomy was performed. Histology revealed end stage pyelonephritis. The calculus consisted of pure xanthine. Further investigations demonstrated low serum uric acid and absent urinary uric acid with increased excretion of xanthine. Eight months after nephrectomy blood pressure had decreased to normal. Her 5-year-old sister, who has beta thalassemia, also has a low serum uric acid concentration and xanthinuria. The treatment of choice is to increase fluid intake so that the urine xanthine concentration remains below the level at which xanthine crystallizes. This may require adjustment of the urine pH. PMID- 3339737 TI - Renal cell carcinoma. PMID- 3339738 TI - Flow cytometric evaluation of urological malignancy. PMID- 3339739 TI - Isolated renal artery dissection secondary to medial degeneration. AB - Renal artery aneurysms can have variable presentations, often resulting in a therapeutic dilemma to the clinician. We review the causes, clinical features, pathological conditions and treatment options for this problem. We report a case of a thrombus in 1 of 2 left renal arteries, which resulted in uncontrollable hypertension. At nephrectomy the angiographically normal vessel had medial degeneration, demonstrating the diffuse nature of this disease. Conservative renal-sparing management should be considered whenever possible. PMID- 3339740 TI - Suprarenal occurrence of an adenomatoid tumor. AB - Adenomatoid tumors are rare, benign mesotheliomas that usually are associated with genito-urinary tract. The suprarenal occurrence of this tumor is uncommon. We present such a case and review the origin of the adenomatoid tumor. PMID- 3339741 TI - Renal cell carcinoma in a solitary kidney: late nephrectomy after 35 years and analysis of tumor deoxyribonucleic acid content. AB - We report a case of renal cell carcinoma in a solitary kidney, which was palpable for 35 years and verified histopathologically 31 years before nephrectomy. Deoxyribonucleic acid analysis of paraffin embedded and new surgical samples showed a similar aneuploid deoxyribonucleic acid content with an index of 1.3. The unusually long survival of this patient is discussed. PMID- 3339742 TI - Acetylcysteine for urinary tract mucolysis. AB - The use of acetylcysteine is described for the relief of mucinous obstruction of the distal ureter after a mid ureteral replacement with ileum. Acetylcysteine (300 cc of 1 per cent) was instilled at low pressure via a nephrostomy tube following documentation of the obstruction with a nephrostogram. Patency of the ureter was achieved within 5 minutes. Re-obstruction ensued but it resolved with repeat percutaneous instillation of acetylcysteine. Patency, confirmed by a followup nuclear renogram at 4 months, has been maintained with 700 mg. acetylcysteine orally 4 times a day. PMID- 3339743 TI - Congenital iliac arteriovenous malformation: a cause of massive hematuria and ureteral obstruction. PMID- 3339744 TI - Malacoplakia: a case involving epididymis and a case involving a bladder complicated by calculi. AB - We report the sixth case of malacoplakia of the epididymis in the world literature and the first to occur in a patient who had undergone a vasectomy previously. The patient was treated successfully by epididymectomy. Another case of malacoplakia of the bladder is reported in which multiple adherent stones developed on the surface of the lesion. Long-term antibiotic therapy led to stabilization of bilateral obstruction at the ureterovesical junction. PMID- 3339745 TI - Extracorporeal shock wave lithotripsy for the treatment of bulbous urethral stones. AB - Extracorporeal shock wave lithotripsy was used to treat multiple, large, bulbous urethral calculi in a paraplegic man. Prior attempt at endoscopic extraction was unsuccessful owing to the size and location of the calculi. Two treatments of 3,000 shocks each resulted in fragmentation of the calculi PMID- 3339746 TI - Erosion of an inflatable penile prosthesis reservoir into the bladder, presenting as bladder calculi. AB - We report a case of erosion of an inflatable penile prosthesis reservoir int the bladder 4 years after implantation for organic impotence. In contrast to previously reported cases this complication was not associated with incontinence, urinary tract infection or a revision procedure. Microscopic hematuria was present but there was no pyuria. Diagnosis evaded radiographic and cystoscopic confirmation. Bladder erosion of the reservoir was discovered incidentally during treatment of bladder calculi. PMID- 3339747 TI - Priapism associated with trazodone therapy. AB - Priapism associated with medication use is well known as one of the most difficult forms of priapism to treat. We report 2 cases of priapism and prolonged erection associated with trazodone therapy. The literature is reviewed and potential treatment options are discussed. PMID- 3339748 TI - Ejaculatory failure and urinary dysfunction secondary to labetalol. AB - We describe 3 men with moderate to severe essential hypertension in whom ejaculatory failure developed after therapy with labetalol, an antihypertensive drug with alpha-1 and beta-adrenergic blocking properties. No decrease in libido or erectile dysfunction was reported by any of the patients. Previous and subsequent antihypertensive therapy with either alpha or beta-adrenergic blocking agents failed to cause similar symptoms. These findings reveal a unique spectrum of genitourinary dysfunction associated with the multireceptor blocking properties of labetalol. PMID- 3339749 TI - Persistent mullerian duct syndrome in a man with transverse testicular ectopia. AB - A 33-year-old Pakistani man with transverse testicular ectopia underwent surgery for repair of a left inguinal hernia. At operation a uterine structure with attached vasa deferentia was found in the left inguinal area and it was removed. Transverse testicular ectopia has been reported previously in association with the persistent mullerian duct syndrome. A deficiency of activity of a mullerian inhibiting substance during gestation is believed to be responsible for this syndrome. Most patients usually are sterile. Cloning of the gene for a mullerian inhibiting substance should permit studies of the pathogenesis of the persistent mullerian duct syndrome. PMID- 3339750 TI - Simple cyst of the rete testis. AB - We report a case of a simple cyst in the upper pole and connected to the mediastinum testis at the rete testis. The cyst appeared to arise from a dilated rete duct, and it was spherical, smooth-walled and filled with clear fluid. The epithelium was lined with a single layer of cuboidal or flattened cells, with no evidence of squamous differentiation. PMID- 3339751 TI - Unusual presentation of sigmoid diverticulitis as an acute scrotum. AB - We report a case of inflammation of the spermatic cord and testicle resulting from a perforated diverticulum of the sigmoid colon. Management included sigmoid resection with diversion, right orchiectomy and debridement of the right groin. To our knowledge this is the first reported case of retroperitoneal necrotizing fasciitis presenting initially as an acute scrotum. PMID- 3339752 TI - Retroperitoneal seminoma with simultaneous occurrence in the prostate. AB - We report a case of retroperitoneal seminoma with simultaneous occurrence in the prostate. The testes were normal on physical and ultrasound examination. In this case a multicentric occurrence of seminoma was considered rather than metastasis from the retroperitoneum to the prostate. Systemic chemotherapy with vincristine, peplomycin and cisplatin was effective for the prostatic as well as the retroperitoneal lesion. PMID- 3339753 TI - Seminal vesicle abscess: the use of computerized coaxial tomography for diagnosis and therapy. AB - Seminal vesicle abscesses are extremely rare and worthy of report. Computerized tomography easily verifies the diagnosis and simplifies the treatment of transurethral incision and drainage. PMID- 3339754 TI - Re: Endourological reconstruction of posterior urethral disruption. PMID- 3339755 TI - Re: Clinical versus urodynamic diagnosis in an incontinent geriatric female population. PMID- 3339757 TI - Re: Urological manifestations of isolated iliac artery aneurysms. PMID- 3339756 TI - Re: Physiology of erection and pharmacological management of impotence. PMID- 3339758 TI - Photosensitization treatment in bladder cancer. PMID- 3339759 TI - Intratumor injection as a more effective means of porphyrin administration for photodynamic therapy. AB - Photodynamic therapy (PDT) with hematoporphyrin derivative (HpD) as the photosensitizer is a promising new cancer treatment. The major drawback of this procedure is the resulting skin photosensitivity. Patients must remain in subdued light for four to six weeks to avoid cutaneous phototoxicity. In this study, we examine the possibility of reducing the skin photosensitization while maintaining the tumor phototoxic effect by administering the drug directly into the tumor. A subcutaneously implanted mouse bladder tumor (MBT-2) was used. HpD was administered either intraperitoneally (I.P.; 20 mg./kg. b.w.) or by intratumor injection (I.T.; 0.4 mg./cc tumor). The concentrations of HpD in tumor and various tissues (skin, muscle, liver, spleen, kidney, bladder and whole blood) were analyzed at various times after the injection, by 3H-HpD method and by a fluorometric method. Results indicated that at three to 96 hours after the administration, porphyrin levels in tumor were about three to 15 times higher by I.T. than by I.P. injection, while the concentrations in skin and other tissues were 1.3 to 10 times lower. Consequently, at 24 hours after injection ratios between tumor to skin porphyrin were 14 to 92 times higher for I.T. than I.P. injection. Higher porphyrin levels in tumor and lower in normal tissues would indicate lower skin photosensitivity, systemic cytotoxicity and possible greater tumor photosensitivity. This method of porphyrin administration may be useful for the PDT of certain single lesions that are accessible for direct injection. PMID- 3339760 TI - Reflex contractions of the ischiocavernosus muscles following electrical and pressure stimulations. AB - In a previous study, we have demonstrated that voluntary muscular contractions of the ischiocavernosus muscles (IC) correlate with changes in intracavernous pressure and, therefore, with penile rigidity. The purpose of our current research project was to verify whether reflex contractions of the IC muscles exist and under what conditions. Our results confirm that reflex contractions occur following electrical or pressure stimulations. Following electrical stimulation, the mean latency of the reflex contractions was 67.5 ms for the IC muscles and 34.9 ms for the bulbocavernosus muscles (BC). Following pressure stimulation, the pressure threshold necessary to elicit contractions of the IC muscles varied between 18.2 mm. Hg and 34.8 mm. Hg. We also observed that pressure variation (increase and decrease) rather than a relatively constant pressure is necessary to produce this reflex response. We interpret these results to suggest that pressure stimulations on the glans penis during coitus contribute to the erectile process and, specifically, to the increase in intracavernous pressure. These findings suggest the possibility of a physiotherapeutic management for patients with penile rigidity problems. PMID- 3339761 TI - Transplantation of immortalized bladder epithelial cell lines in denuded mouse bladder. AB - The temporal and spatial regeneration of denuded mouse bladders was characterized using antibody markers to mucosal and submucosal elements in bladder tissue. Mechanical stripping of bladder mucosa resulted in a plane of cleavage in the submucosa leaving the muscle layers intact. Fully regenerated bladders were observed after 14 to 21 days although submucosal elements showed abnormal vacuolation. Implantation of immortalized epithelial cell line BBN3 into denuded bladders resulted in solid tumor formation while, in contrast, transplantation of MB331 showed cystic structures with no indication of invasion. Confirmation of the epithelial and implanted origin of cells lining the lumina of implanted bladders were shown using different keratin antibodies. The benign behavior of MB331 in vivo is suggestive of a cell line representing a preneoplastic stage in carcinogenesis and demonstrates an approach to assess the in vivo phenotype of cell parameters established in vitro. PMID- 3339762 TI - Laser welding in urethral surgery: improved results with a protein solder. AB - Reconstruction of the rat urethra using the CO2 laser and a protein solder has dramatically decreased the postoperative fistula rate and decreased surgical time over conventional microsurgical reconstruction. Using the rat as a model, a partial transection of the ventral urethra was repaired in one of three ways in 39 animals: conventional microsuture repair, laser assisted microsuture repair and laser assisted microsuture repair with a protein solder. The success rate in each group was 50%, 58% and 90% respectively. Therefore, the laser repair is an efficacious as conventional microsuture repair. More importantly, laser with solder is significantly better than either the conventional method or laser alone. PMID- 3339763 TI - In vitro precipitation of calcium oxalate in the presence of whole matrix or lipid components of the urinary stones. AB - Organic matrix of human calcium oxalate urinary stones was obtained by demineralizing with EDTA. Lipids were extracted from the EDTA-insoluble matrix by chloroform methanol treatment. The whole matrix and its total lipid extract were then incubated in a metastable solution of calcium oxalate and depletion of calcium and oxalate ions from the calcifying solution was determined. Results of our studies described here show that urinary calcium oxalate stone matrix and its total lipid contents were capable of binding calcium and oxalate ions and of catalysing calcium oxalate crystal formation from a metastable calcium oxalate solution. PMID- 3339764 TI - Contraction of urinary bladder by central norepinephrine originating in the locus coeruleus. AB - Studies were performed to elucidate the role of the locus coeruleus, which is rich in norepinephrine-containing cell bodies, in vesical function using alpha chloralose anesthetized cats. Stimulation of the locus coeruleus caused contraction of the urinary bladder, which was not affected by transection of the bilateral hypogastric nerves, but blocked by intravenous administration of hexamethonium, a ganglion blocking agent. In animals with transected hypogastric nerves, the locus coeruleus-induced contraction was inhibited by intrathecal administration of phentolamine (alpha-blocker) and prazosin (alpha 1-blocker), but not affected by intrathecal sotalol (beta-blocker) or yohimbine (alpha 2 blocker). In animals treated with reserpine, the locus coeruleus-induced contraction was enhanced by intravenous application of L-dopa, a precursor of norepinephrine. These results suggest that norepinephrine derived from the locus coeruleus activated preganglionic neurons in the sacral intermediolateral nuclei via alpha 1-receptors, thereby producing urinary bladder contraction. PMID- 3339765 TI - Nerve-sparing retroperitoneal lymphadenectomy for nonseminomatous testicular cancer. PMID- 3339766 TI - Vascular surgery--a continuing quest for excellence. PMID- 3339767 TI - Hemodynamics and prostacyclin release in the early phases of aortic surgery: comparison of transabdominal and retroperitoneal approaches. AB - Although the retroperitoneal aortic approach (RP) is advocated to reduce myocardial ischemia and cardiac-related death, inadequate physiologic data exist to support this contention. As the aorta is exposed via the transabdominal approach (TA) we noted some patients have manifested reduced systemic vascular resistance (SVR) associated with tachycardia, reduced blood pressure, and facial flushing. To determine whether RP offered physiologic advantages over TA we compared cardiac dynamics and blood levels of 6-keto-prostaglandin F1 alpha (6 keto-PGF1 alpha), the stable metabolite of prostacyclin, during exposure of the aorta in 52 patients (33 with TA and 19 with RP), comparable in age, cardiac history, medications, and body surface area. Serial measurements of mean arterial pressure, heart rate, wedge pressure, pulmonary artery pressure, cardiac index, and 6-keto-PGF1 alpha were obtained. Results revealed decreased mean arterial pressure and systemic vascular resistance, increased cardiac index and heart rate, and facial flush occurring 10 minutes after the bowel was explored in TA. This was not observed in RP. These hemodynamic alterations correlated in time and magnitude with a fourteen fold increase in 6-keto-PGF1 alpha. These changes in cardiac indexes can produce increased myocardial oxygen consumption with the risk for myocardial ischemia, particularly in patients with coronary artery disease. The absence of this response to bowel exploration in RP may account for some of the observed advantages in "high-risk" aortic reconstruction. PMID- 3339768 TI - The significance of cerebral infarction and atrophy in patients with amaurosis fugax and transient ischemic attacks in relation to internal carotid artery stenosis: a preliminary report. AB - There is a growing appreciation for the high incidence of silent cerebral infarction and cerebral atrophy on CT scans in patients with amaurosis fugax (AF) and hemispheric transient ischemic attacks (TIAs). Seventy patients with AF only (no TIAs), 104 patients with hemispheric TIAs (no AF), 185 patients without focal carotid territory symptoms (i.e., vertebrobasilar TIAs or asymptomatic carotid bruit only), and 129 patients with stroke and good recovery were studied with CT scan and duplex scanning to grade the degree of stenosis of the internal carotid artery (grades: A = normal, B = 0% to 15% stenosis, C = 16% to 49%, D = 50% to 99%, and E = occlusion). In patients with AF, the incidence of infarction increased from 20% in grades A, B, and C to 40% in grade D and 58% in grade E. The incidence of atrophy increased in parallel from 10% in grade A to 30% in grade E. The increased incidence of atrophy with increasing degrees of stenosis was not the result of increasing degrees of stenosis per se, but the associated increase in the incidence of infarction (patients without CT infarcts in grades D and E had 5% and 0% incidence of atrophy). In patients with hemispheric TIAs, the incidence of CT infarction increased from 25% in grades A and B to 48% in grades D and E. The incidence of atrophy did not show a parallel increase. Our findings support the hypothesis that atrophy is associated not only with cerebral infarction but may be causally related.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339769 TI - Carotid endarterectomy with local anesthesia: results and advantages. AB - In a collaborative prospective study from two institutions, we reviewed the clinical course of 969 consecutive patients who had 1200 carotid endarterectomies (CEs) for the treatment of occlusive arterial disease during the period 1977 to 1987. The indications for CE comprised transient ischemic attacks (TIAs) in 581 cases (48.4%), cerebral infarction (CI) in 170 (14.2%), monocular blindness in 166 (13.8%), and asymptomatic stenosis in 283 (23.6%). Neurologic monitoring of the awake patient provided more reliable indication of the need for brain protection during operative arterial clamping than did electroencephalography or carotid stump pressure measurement. Of the 1200 cases, 113 (9%) required a shunt as determined by this method. Patients with contralateral carotid occlusion or severe stenosis required shunting six times more frequently than those with a unilateral lesion. Among all procedures, there were nine cases of transient neurologic deficit (0.9%), 11 cases of permanent neurologic deficit (0.9%), and eight deaths (0.67%). Among 283 CEs performed to treat asymptomatic lesions, no strokes and only one death (0.4%) occurred. One hundred sixty-six cases with amaurosis fugax were operated on without stroke or death. In the age group of 70 to 90 years, 508 procedures were carried out with four deaths (0.8%) and three strokes (0.6%). We conclude that CE performed with the patient under local anesthesia is safe and effective and permits satisfactory management of old and high-risk patients. PMID- 3339771 TI - Carotid endarterectomy in a metropolitan community: the early results after 8535 operations. AB - Several retrospective community surveys have provoked speculation concerning the safety of carotid endarterectomy (CEA) throughout the United States. To address this serious issue, surgical outcome was calculated for 8535 CEAs entered prospectively into a computer registry by 51 trained vascular surgeons in a large metropolitan area from 1973 to 1985. A total of 7480 procedures (88%) were performed for symptomatic lesions and 1055 (12%) were performed for asymptomatic stenosis or ulceration. There were 178 operative strokes (2.1%) and 135 early deaths (1.6%), for a combined morbidity-mortality rate of 3.2%. Fatal events were attributed to cardiac disease in 0.7%, neurologic complications in 0.6%, and other causes in 0.3%. The stroke rate (n = 148; 2.0%) in symptomatic patients was better than that in asymptomatic patients (n = 30; 2.8%) (chi 2 = 5.2; p less than 0.025), but the combined morbidity-mortality rates (2.9% and 3.7%) were not statistically different. The incidence of stroke reported by surgeons who performed more than 5 CEAs annually (1.7%) was statistically superior to the stroke rate (3.4%) among those with less experience (chi 2 = 37.1; p less than 0.0001). Nevertheless, both groups had acceptable results that were consistent with their training and continued interest in vascular surgery. PMID- 3339770 TI - Intracranial hemorrhage after carotid endarterectomy. AB - Among 1500 carotid endarterectomies performed between 1975 and 1984, 11 ipsilateral intracranial hemorrhages (IH) occurred between the first and tenth postoperative days for an incidence of 0.7%. The mortality rate among these patients was 36%. The only recognizable predisposing factor was relief of high grade carotid stenosis (greater than 90%) whereas other factors such as age (58 to 81 years), preoperative hypertension (systolic blood pressure 120 to 160 mm Hg), preoperative head CT scans showing recent infarction (only one in five positive), and preoperative cerebral infarction (only 1 of 11 patients) did not play a role. All patients had normal coagulation studies. No patient required a shunt because all tolerated cross-clamping of the carotid artery. Postoperative systolic blood pressures were 200 to 240 mm Hg in 6 of 11 patients. The time of occurrence of IH extended from the immediate postoperative period to the tenth postoperative day (mean interval 3.3 days). Treatment consisted of craniotomy in five patients; four survived and one recovered completely. Of the six patients treated nonoperatively, three survived and two completely recovered. IH shares equal incidence with recurrent thrombosis, cross-clamping ischemia, and embolization as a cause of perioperative stroke. Although all except IH can be prevented by current practice, the means of preventing IH are not apparent; however, careful monitoring of blood pressure to prevent uncontrolled hypertension deserves consideration. PMID- 3339772 TI - Removal of focal atheromatous lesions by angioscopically guided high-speed rotary atherectomy. Preliminary experimental observations. AB - A new high-speed rotary atherectomy device, inserted over a guide wire and directed with an angioscope, offers the potential of restoring patency of outflow vessels by "boring out" the atheromatous lesion of the orifices of runoff vessels. The device was tested on 68 cadaver arteries with atheromatous lesions involving the superficial femoral, popliteal, and tibial arteries. This was performed with either free segments or in situ with the device placed through a popliteal arteriotomy. The gross results of rotary atherectomy were assessed by angioscopy, angiography, or both. The luminal surfaces were studied with scanning electron microscopy and transverse sections of vessels were studied with light microscopy. The pulverized atheroma, in colloidal suspension, was analyzed for particle size by Coulter counter. The effect of a colloidal suspension of atheromatous particles on distal capillary circulation was measured in animal experiments. Obstructive lesions were successfully removed in 36 of 37 stenotic arteries (97%) and 18 of 31 completely occluded arteries (58%), an overall efficacy of 54 of 68 (79%). In successfully atherectomized arteries, angioscopy and angiography demonstrated a widely patent, smooth, polished surface. Light microscopy demonstrated removal of the diseased intima with maintenance of the outer media and adventitia. The pulverized atheroma particles were generally smaller than red blood cells and injection of the colloidal atheroma into canine femoral arteries failed to produce local tissue injury. We conclude that in the human cadaver this atherectomy device effectively enlarges and recanalizes obstructed superficial femoral, popliteal, and tibial arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339773 TI - The effects of pentoxifylline on patients with intermittent claudication. AB - All patients who had intermittent claudication (IC) over an 18-month period were given prescriptions for pentoxifylline (PTFX) 400 mg, three times daily. Patients were required to purchase their medication at a cost of $28 to $35 per month. The drug was administered regardless of the severity of symptoms, and no patient was offered operation without at least a 6-week trial of PTFX. An assessment of the severity of IC was made at the initial visit based on noninvasive data and the impact of the IC on the patient's life-style. One hundred thirty patients were enrolled in the study and were followed for 9 +/- 1 months. Patients were seen every 2 months for treadmill exercise or induced hyperemic testing and interviews until the effects of the medication were determined. The duration of IC before the start of treatment had no effect on the results. IC did not improve in 88 patients (71%) followed for 7.2 +/- 1 month. Thirty-six of these patients stopped the drug themselves because there was no benefit and the expense of PTFX was a hardship. An initial but short-lived improvement in walking was noted in another 13 patients (10%) following 14 +/- 2 months, and the medication was eventually discontinued. Only 23 patients (19%) followed for 11.6 +/- 2 months felt that IC had improved to the point where they did not feel limited in any way. Gastrointestinal symptoms occurred in 13 patients and were severe in eight patients (6%) who stopped taking the medication. The results of PTFX in this group of patients with IC were disappointing at best.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339774 TI - Short vein grafts: a superior option for arterial reconstructions to poor or compromised outflow tracts? AB - To determine whether vein graft length is a factor that influences infrapopliteal bypass patency, we reviewed 237 consecutive reversed saphenous vein bypasses performed because of critical ischemia during a 5-year period. One hundred seventeen long vein grafts (LVGs) were longer than 40 cm (42 to 92 cm, mean 60.9 +/- 9 cm) and 120 short vein grafts (SVGs) were 40 cm or shorter (6 to 40 cm, mean 24.7 +/- 8 cm). Ninety-three percent of the LVGs originated from or were proximal to the superficial femoral artery (SFA) whereas all of the SVGs originated at or distal to the SFA. The cumulative patency rate for LVGs at 3 years was 45% and for SVGs was 63% (p less than 0.025). In the absence of an intact pedal arch, 3-year patency rates for LVGs (51 cases) and SVGs (78 cases) were 22% and 53%, respectively (p less than 0.01). High intraoperative outflow resistance measurements (greater than 0.7 mm Hg/ml/min) were encountered in 25 cases. Of these, occlusion within 6 months occurred in six of seven cases with LVGs and in only 8 of 18 cases with SVGs (p less than 0.05). Wound complications at vein harvest sites occurred in 17% of LVGs and in only 6% of SVGs (p less than 0.01). Of 16 additional cases in which a proximal patch angioplasty or percutaneous transluminal angioplasty was performed tandem with a short distal vein graft, four occluded (less than 6 months) and 12 remained patent from 3 to 43 months (mean 12.6 months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3339775 TI - National Research Council endorses human gene mapping project. PMID- 3339776 TI - One way 'the latest health news' may benefit patients through physicians' response. PMID- 3339777 TI - Dietary cholesterol still a lively discussion topic. PMID- 3339778 TI - Court ruling expected soon in alcoholism case. PMID- 3339780 TI - Alzheimer's disease: unskilled vulgarity decays into stunning artistic genius. PMID- 3339779 TI - Leads from the MMWR. La Crosse encephalitis in West Virginia. PMID- 3339782 TI - A dip in the pool. PMID- 3339781 TI - The treatment of neurosyphilis in patients with HIV infection. PMID- 3339784 TI - Clotrimazole troches vs oral nystatin for oropharyngeal candidiasis. PMID- 3339783 TI - Occupation and coronary disease: schooling as a confounder. PMID- 3339785 TI - Dressing regimens and intravenous catheter-related infections. PMID- 3339786 TI - Philadelphia General Hospital. PMID- 3339787 TI - Research: biased fox guards data henhouse. PMID- 3339788 TI - Local anesthesia for neonatal circumcision. Effects on distress and cortisol response. AB - A controlled, double-blind investigation was conducted to determine whether the dorsal penile nerve block using lidocaine hydrochloride without epinephrine would effectively reduce behavioral distress and adrenocortical responses to routine neonatal circumcision. The subjects were healthy male newborns whose parents had requested circumcision. Equal numbers (n = 20) were randomly assigned to circumcision with lidocaine, saline, or no injection. Dorsal penile nerve block was found to be a safe and easy technique that was effective in reducing behavioral distress and modifying the adrenocortical stress response. The injection itself did not increase stress reactions and did not offset the beneficial effects of anesthesia. If circumcisions are to be performed, they should be done as humanely as possible. PMID- 3339789 TI - Body mass index and mortality among nonsmoking older persons. The Framingham Heart Study. AB - The relationship of weight at age 65 years and subsequent mortality was examined in a population of 1723 nonsmokers who were followed up from one to 23 years (mean, 9.5 years) during the Framingham Heart Study. In sex-specific proportional hazards analyses, risks of mortality were increased for men and women at the high and low extremes of body mass index, even when accounting for potential effects of excess weight on serum cholesterol level, blood glucose level, and systolic blood pressure. For those at the lower extreme of body mass index, the relative risk of death was almost twice as high in the years immediately after age 65 years as in later follow-up, suggesting that the increased early death rate was due to disease that was already present. At the upper extreme, risk of death was twofold over the entire follow-up period for persons with body mass indexes at or above the 70th percentile at both 55 and 65 years of age. We conclude that, even when accounting for cardiovascular risk factors, being overweight is a serious health problem for older people, especially for those with long-standing weight problems. PMID- 3339790 TI - Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial. AB - To test whether changes in folate and vitamin B12 nutrition modify the severity of potentially premalignant lesions identified by cytology in sputum samples of smokers, we conducted a randomized, controlled prospective intervention trial in smokers with bronchial squamous metaplasia. Seventy-three men with a history of 20 or more pack-years of cigarette smoking who had metaplasia on one or more sputum samples were stratified according to smoking level and randomly assigned to four months' treatment with either placebo or 10 mg of folate plus 500 micrograms of hydroxocobalamin. Direct cytological comparison of the two groups after four months showed significantly greater reduction of atypia in the supplemented group. This provides preliminary evidence that atypical bronchial squamous metaplasia may be reduced by supplementation with folate and vitamin B12. However, the significance of these findings is tempered by substantial spontaneous variation in sputum cytologies, the small study population, the short duration of the trial, and the supraphysiological doses of folate and B12 used. The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B12 by smokers. PMID- 3339792 TI - Mammography before age 50 years? PMID- 3339791 TI - The legal concept of wrongful life. PMID- 3339793 TI - Diagnostic and therapeutic technology assessment. Ureteral stone management: II. Ureteroscopy and ultrasonic lithotripsy. PMID- 3339795 TI - Why teachers with AIDS belong in the classroom. PMID- 3339794 TI - A piece of my mind. It's over, Debbie. PMID- 3339796 TI - CONTEMPO '87 crushes, disturbs, saddens, amazes, and disappoints. PMID- 3339798 TI - The 'barely veiled warning'. PMID- 3339797 TI - Beer, breast-feeding, and the wisdom of old wives. PMID- 3339799 TI - Cigarette smoking as a risk factor for stroke. The Framingham Study. AB - The impact of cigarette smoking on stroke incidence was assessed in the Framingham Heart Study cohort of 4255 men and women who were aged 36 to 68 years and free of stroke and transient ischemic attacks. During 26 years of follow-up, 459 strokes occurred. Regardless of smoking status and in each sex, hypertensive subjects had twice the incidence of stroke. Using the Cox proportional hazard regression method, smoking was significantly related to stroke after age and hypertension were taken into account. Even after pertinent cardiovascular disease risk factors were added to the Cox model, cigarette smoking continued to make a significant independent contribution to the risk of stroke generally and brain infarction specifically. The risk of stroke increased as the number of cigarettes smoked increased. The relative risk of stroke in heavy smokers (greater than 40 cigarettes per day) was twice that of light smokers (fewer than ten cigarettes per day). Lapsed smokers developed stroke at the same level as nonsmokers soon after stopping. Stroke risk decreased significantly by two years and was at the level of nonsmokers by five years after cessation of cigarette smoking. PMID- 3339800 TI - Silent ischemia on Holter monitoring predicts mortality in high-risk postinfarction patients. AB - The relative prognostic significance of ischemic ST changes on two-lead continuous electrocardiographic (Holter) monitoring in 103 high-risk postinfarction patients was examined. Ischemic ST changes were detected in 30 patients, with a median number of five episodes per day and median total daily duration of 157 minutes. Only one third of these patients reported any angina in the hospital, and 28 of the 30 patients had silent ST changes on Holter monitoring. The remaining 73 patients had no ischemic ST changes on Holter monitoring. At one year, nine (30%) of 30 patients with ischemic ST changes were dead vs only eight (11%) of 73 patients without such changes. Multivariate Cox's hazard function analysis on 18 variables, including age, type of infarction, Lown and Killip class, ejection fraction, and medications, showed that the presence of ST changes on Holter monitoring was a significant predictive variable for one year mortality in the overall study population and particularly in the subgroup of 59 patients who could not undergo early exercise treadmill testing. Thus, ischemic ST changes on Holter monitoring, the majority of which are silent, occur in nearly one third of high-risk postinfarction patients and are significantly associated with one-year mortality. PMID- 3339801 TI - Health education on the six-o'clock news. Motivating television coverage of news in medicine. AB - Prepackaged video news releases are being increasingly used to motivate television stations to cover stories in medicine and public health in their news programs. On Feb 26, 1987, the Office on Smoking and Health, US Department of Health and Human Services, distributed a prepackaged video news release to television stations across the country, calling attention to the new health warnings required on smokeless tobacco packages and advertisements. The video was sent by satellite as well as by overnight mail to selected stations. To assess the use of the video, we surveyed 76 stations that had been targeted by special intervention. These stations were in major metropolitan areas in states with a higher prevalence of smokeless tobacco use. Seventeen (22.4%) of the stations aired the story using our video during the six days following the satellite feed, reaching an estimated 2.8 million households. Another 20 stations reported that they were holding the video for use in the near future or for file footage. We conclude that the distribution of prepackaged video news stories can be an effective, relatively inexpensive technique to communicate health information to a large audience. PMID- 3339802 TI - Relapse of herpes simplex encephalitis after conventional acyclovir therapy. AB - Acyclovir sodium is the drug of choice for the treatment of herpes simplex encephalitis. We treated an immunocompetent patient with a ten-day course of intravenous acyclovir sodium at the recommended dosage of 10 mg/kg every eight hours for clinically apparent herpes simplex encephalitis. After marked improvement, his condition deteriorated four days after completing acyclovir therapy. A subsequent brain biopsy specimen disclosed acyclovir-sensitive herpes simplex virus type 1. A longer duration of acyclovir therapy (14 to 21 days) should be considered for treating herpes simplex encephalitis. PMID- 3339803 TI - Disseminated herpes simplex infection in a neonate during prophylaxis with vidarabine. PMID- 3339804 TI - Report on the accreditation process. Council on Medical Education. AB - The continuing participation of the AMA in the accreditation of medical education is consistent with the responsibility of the medical profession for the quality of each level of medical education. The Council on Medical Education will continue to monitor and recommend improvements in an essentially sound and effective accreditation system. The ultimate purpose of accreditation is to improve the quality of medical care through education, research, and service. The Council will report further developments as indicated. The Council of Medical Education recommends that the AMA continue its participation in the accreditation of each level of medical education. PMID- 3339805 TI - The frustrations of treating herpes simplex virus infections of the central nervous system. PMID- 3339806 TI - The revised Uniform Requirements of the Vancouver Group. PMID- 3339807 TI - Preliminary evidence points to affective disorder triggered by summer weather. PMID- 3339808 TI - Sleep patterns scrutinized as depression therapy. PMID- 3339809 TI - Studying oxygen's life-and-death roles if taken from or reintroduced into tissue. PMID- 3339810 TI - Leads from the MMWR. Antigenic variation of recent influenza A(H3N2) viruses. PMID- 3339811 TI - Leads from the MMWR. Continuing increase in infectious syphilis--United States. PMID- 3339812 TI - Leaders attempt a long-term prognosis for the health of American medicine. PMID- 3339813 TI - While coping with this season's influenza, experts plan for season still to come. PMID- 3339814 TI - Do power line-generated electromagnetic fields have any association with certain disorders? PMID- 3339815 TI - Leads from the MMWR. Screening for cervical and breast cancer--southeastern Kentucky. PMID- 3339816 TI - Leads from the MMWR. Changes in premature mortality--United States, 1979-1986. PMID- 3339817 TI - Why was the policeman's lot unhappy? More flak jacketing. PMID- 3339818 TI - Cholesterol emboli and streptokinase therapy. PMID- 3339819 TI - Anemia in low-income children. PMID- 3339820 TI - Identifying mobility dysfunctions in elderly patients. Standard neuromuscular examination or direct assessment? AB - The need to assess functions such as mobility in elderly patients is increasingly recognized. Lacking other methods, clinicians may rely on the standard neuromuscular examination to evaluate mobility. Therefore, we checked the sensitivity of the neuromuscular examination for identifying mobility problems by comparing relevant neuromuscular findings with performance during four routine mobility maneuvers: (1) getting up from a chair, (2) sitting down, (3) turning while walking, and (4) raising the feet while walking. The subjects investigated were 336 elderly persons living in the community. Many subjects who performed poorly during mobility maneuvers did not have the corresponding neuromuscular abnormalities. For example, although hip and knee flexion are needed to sit down safely, abnormal hip flexion was found in only 15% and abnormal knee flexion in only 30% of the subjects who had difficulty sitting down. The relationship between neuromuscular findings and functional mobility was not predictable enough to rely on neuromuscular findings for identifying mobility problems. Therefore, a simple assessment that reproduces routine daily mobility maneuvers should be developed for use in the clinical care of elderly patients. PMID- 3339822 TI - The assessment and treatment of geezers. PMID- 3339823 TI - First needle-exchange program approved; other cities await results. PMID- 3339824 TI - Pediatric vaccine tax seeks to cover injury; not all manufacturers passing on increase. PMID- 3339821 TI - Computer predictions of abnormal test results. Effects on outpatient testing. AB - We developed statistical equations to predict abnormalities on eight commonly ordered diagnostic tests and we gave the predictions to 112 physicians practicing in an academic internal medicine practice. Half of each physician's patients were randomized to intervention status. All diagnostic tests were ordered by microcomputer, and when a physician ordered one of the eight study tests for an intervention patient, the computer displayed the probability (0% to 100%) that the test would be positive for the main abnormality being tested for. The physician could then cancel the test if desired. During a six-month controlled trial, when there were more than 15,000 scheduled patient visits, patient charges for the eight study tests were 8.8% less for the intervention patients. The largest reductions (greater than 10%) were for serum electrolyte level tests and complete blood cell counts, the two most commonly ordered tests. Physicians ordered fewer low-probability tests for intervention patients than for controls, suggesting that with timely predictive information, physicians can target tests to higher-risk patients. PMID- 3339825 TI - Laboratory to study micronutrients, cancer risk as part of chemoprevention efforts. PMID- 3339826 TI - Leads from the MMWR. Semen banking, organ and tissue transplantation, and HIV antibody testing. PMID- 3339827 TI - Leads from the MMWR. Acute respiratory illness among cruise-ship passengers- Asia. PMID- 3339828 TI - Leads from the MMWR. Measles--United States, first 26 weeks, 1987. PMID- 3339829 TI - Jessica in the well: ischemia and reperfusion injury. PMID- 3339830 TI - Sigmoidoscopy: blaming the tools. PMID- 3339831 TI - The repair of umbilical hernia: unvoiced assumptions and sex. PMID- 3339832 TI - The biologic effects of low-level radiation. PMID- 3339834 TI - The Resource-Based Relative Value Scale. PMID- 3339833 TI - Esophageal candidiasis in the diagnosis of HIV-infected patients. PMID- 3339836 TI - OD or not OD? PMID- 3339835 TI - Calcium in electromechanical dissociation. PMID- 3339837 TI - Increased risk of suicide in persons with AIDS. AB - The rate of suicide has been reported to be higher in persons with chronic and life-threatening illnesses (eg, cancer, Huntington's disease, and renal failure). We studied the rate of suicide in 1985 in New York City residents diagnosed with the acquired immunodeficiency syndrome (AIDS). There were 668 suicides in New York City residents in 1985, yielding a rate of 9.29 per 100,000 person-years. In men aged 20 to 59 years without a known diagnosis of AIDS, the rate was 18.75 per 100,000 person-years. There were 3828 individuals who lived with the diagnosis of AIDS for some part, or all, of 1985. There were 12 suicides in men aged 20 to 59 years from this group who lived 1763.25 person-years with a diagnosis of AIDS. This yields a suicide rate of 680.56 per 100,000 person-years. Thus, the relative risk of suicide in men with AIDS aged 20 to 59 years was 36.30 times (95% confidence limits, 20.45 to 64.42) that of men aged 20 to 59 years without this diagnosis, and 66.15 times (95% confidence limits, 37.38 to 117.06) that of the general population. We conclude that AIDS represents a significant risk factor for suicide. PMID- 3339838 TI - Investigations of AIDS patients with no previously identified risk factors. AB - Through Sept 30, 1987, two thousand fifty-nine patients with acquired immunodeficiency syndrome (AIDS) and no recognized risk factors were reported to the Centers for Disease Control. Risk history was incomplete or unobtainable for 921 (45%) of them. Risk factors were ultimately identified for 825 (72%) of the remaining 1138. Another 32 persons (3%) did not meet the case definition for AIDS. Risk factors could not be identified for the remaining 281 patients (25%), despite additional information. Of these, 178 (63%) were interviewed with standard questionnaires; 38% reported sexually transmitted diseases and 34% of the men reported sexual contact with prostitutes. There was no evidence for new transmission modes. Although the proportion of AIDS patients with undetermined risk factors has increased significantly during the past year, the adjusted proportion shows no significant change over time. Thus, follow-up of AIDS patients with no apparent risk factors suggests that modes of transmission for human immunodeficiency virus have remained stable. PMID- 3339839 TI - Use of the hospital in a randomized trial of prepaid care. AB - Health maintenance organizations (HMOs) achieve their cost savings through lower rates of hospital admissions. To determine whether HMOs selectively avoid discretionary hospitalizations, medical records were reviewed from a randomized trial where families were assigned to either HMO or free-for-service care. Physicians who were blinded to system reviewed 244 medical records and judged the appropriateness both of the hospital setting and of the medical indications for hospitalization. The rate of discretionary surgery was lower in the HMO, while the rate of nondiscretionary surgery was equivalent in the two systems. For medical admissions, rates of discretionary and nondiscretionary admissions were lower in the HMO. There were no observable adverse effects on health from the lower rates of nondiscretionary hospitalization, either because the net effect on health was small or because the HMO substituted appropriate ambulatory services. We conclude that HMO reductions in hospitalization rates do not occur "across the board"; discretionary surgery is selectively avoided. PMID- 3339840 TI - Cat-scratch disease. Isolation and culture of the bacterial agent. AB - A gram-negative bacterium or its cell wall-defective variants were isolated from lymph nodes of ten patients with cat-scratch disease. Cultured bacteria were morphologically identical to vegetative and wall-defective forms seen in human tissues. Three of seven patients with recent cat-scratch disease had fourfold or greater rises in antibody titer against the cultured bacteria; the remaining four patients had maximum titers of 1:32 to 1:128. Rabbit antiserum to cultured bacilli reacted in immunoperoxidase stains with vegetative and wall-defective cat scratch disease bacilli in lymph node, skin, or conjunctiva and with vegetative or wall-defective bacteria isolated from ten patients. Vegetative bacteria produced lesions in the skin of an armadillo identical to early lesions in human skin. Vegetative bacteria were recovered from the lesions in the armadillo. PMID- 3339841 TI - Ethical issues involved in the growing AIDS crisis. Council on Ethical and Judicial Affairs. PMID- 3339842 TI - Caring for the patient with AIDS. PMID- 3339843 TI - AIDS and suicide. PMID- 3339844 TI - Diagnostic and therapeutic technology assessment. Ureteral stone management: the use of ureteroscopy with extracorporeal shockwave lithotripsy or ultrasonic lithotripsy. PMID- 3339845 TI - [Urinary bladder tumor manifesting multiple bone metastases similar to prostatic carcinoma--a case report]. AB - A 72-year-old patient was found to have a non-papillary bladder tumor extending from the vesical floor to the retrotrigone and manifested multiple bone metastases without evidence of any hematogenic metastases in other organs. The pattern of the above metastases were very similar to that of a prostatic carcinoma and suggests that the so-called specific pattern of bone metastases observed in prostatic carcinomas might be caused by the location of the original tumor and not by features of the prostatic carcinoma cells themselves. PMID- 3339846 TI - [Multiple primary malignant tumors of rhabdomyosarcoma in an upper arm and breast cancer]. AB - Multiple primary malignant tumors of rhabdomyosarcoma in a upper arm and cancer of breast are extremely rare. In September 1970, a female, aged 86 years, underwent the first resection operation performed on a pleomorphic rhabdomyosarcoma of the right upper arm. She underwent radiation therapy (8000 rads at the operative field) postoperatively. In August 1980, a simple mastectomy was performed for a cancer of the right breast. In December 1984, fourteen years after her first operation, a recurrence was detected. The tumor recurred five times during the next two years and was resected each time. The patient died of cachexia sixteen years after the first operation. PMID- 3339847 TI - [Adenoma of the breast: histopathological study of 9 cases]. AB - Adenomas of the breast are cellular epithelial lesions, which are subclassified into two types, tubular adenomas (TA) and lactating adenomas (LA). In 3365 cases of benign epithelial tumors of the breast, including fibroadenomas, filed in the Hiroshima Tumor Tissue Registry between 1973 to 1985, only nine adenomas (TA-4, LA-5) or 0.3% were filed. All adenoma cases involved females, with an average of 27.4 years. Grossly, the tumors were found to vary from 1.5 to 5 cm in diameter and were sharply demarcated. Microscopically and ultrastructurally, the small tubules found in TA are identical to normal ducts. According to progress from pregnancy to lactation, the tubular tissue in LA demonstrate breast increasing secretory activities. The absence of TA during pregnancy, the structural similarity and the fact that some LA had already developed into a palpable mass before pregnancy are signs that indicate that all TA and LA share the same biologic process. PMID- 3339848 TI - [Necessity of adjuvant therapy after radical mastectomy based on a study of patients with negative nodes, who have recurrent breast cancer]. AB - The status of the regional lymph nodes influences the prognosis of women with breast cancer who have received a radical mastectomy. To investigate the characteristics of patients with negative nodes who have had a recurrent breast cancer, a statistical study has been carried out involving 279 women who had received a radical mastectomy in our hospital from July 1970 to October 1986. From this study we conclude that systemic adjuvant therapy after radical mastectomy is necessary for patients with negative nodes who have had a breast cancer greater than 2.1 cm (T2) in diameter or a solid-tubular carcinoma. PMID- 3339849 TI - [Evaluation of para-aortic lymph node metastases in patients with cervical cancer]. AB - From 1979 to 1986, 355 patients with cervical cancer underwent paraaortic lymph node (PAN) biopsy before the start of initial treatment. Nineteen of these 355 patients (5.4%) had a positive PAN, and the percentage incidence of positive PAN in each clinical stage was as follow: stage Ib, 2.4%; IIa, 0%; IIb, 3.7%; IIIb, 19.0%; and IV, 20%. Eighteen of these 19 patients also had positive pelvic lymph nodes. Positive PANs were found to be more frequent in cases of an adenocarcinoma than in cases of squamous cancer. The palpation of the PANs seemed to be too insufficient to predict the metastasis. Patients with positive PAN who had received paraaortic irradiation survived longer than those who did not receive such treatment. It is concluded that the evaluation of the PAN is important for the management of a cervical cancer. PMID- 3339850 TI - [Stromal sarcoma of the breast following augmentation mammoplasty--a case report]. AB - A case of a stromal sarcoma of the breast that developed after augmentation mammoplasty is presented. A 55-year-old woman, who had received mammoplasty twenty years earlier, was referred to our hospital due to a mass in her left breast. A diagnosis of myxoid sarcoma was determined by an incisional biopsy and a radical mastectomy was performed. A pathological specimen, however, revealed the mass to be a stromal sarcoma because of its metaplastic heterogeneous elements, such as bone, cartilage, and muscle. We also present previous cases, and discuss the matter of diagnosis and therapy. PMID- 3339851 TI - [Policies for clinical trials in cancer]. AB - The importance of proper planning, organization, and design of cancer clinical trials along with the need for a clear and detailed protocol cannot be overemphasized since these factor are crucial in determining the eventual success of a study. Of course, all clinical trials should be ethically and scientifically justified. In this context, we organized two committees, Protocol Review Committee and Monitoring Committee, for the cancer clinical trials conducted in a study group performing a project, "study of multidisciplinary treatment of solid cancer", supported by a Grant-in-Aid (62 S-1) for Cancer Research from the Ministry of Health and Welfare, in order to judge ethical and scientific problems of the protocols as well as the interim and final analyses of results. Here, we described stipulations of the Committees for proper design and conduct of the protocol study. PMID- 3339852 TI - "AIDS" infection control policies for Kansas health care agencies and "AIDS" education for registered nurses in Kansas: final report. PMID- 3339853 TI - AIDS and maternal child care. PMID- 3339854 TI - Values: a descriptive study of professional students in nursing. PMID- 3339855 TI - Kansas AIDS task force. PMID- 3339856 TI - Risk v. responsibility in providing nursing care: a statement of the ANA Committee on Ethics. PMID- 3339857 TI - AIDS knowledge and attitudes. Provisional data from the National Health Interview Survey: United States, August 1987. PMID- 3339858 TI - AIDS and children. PMID- 3339859 TI - Development of renal lesions in dogs after 11/12 reduction of renal mass. Influences of dietary protein intake. AB - Renal failure was induced in 15 normal Beagle dogs by ligation of approximately 5/6 of the renal arteries of the left kidney and contralateral nephrectomy in order to determine how: (a) 11/12 reduction in total renal mass influences urine protein excretion and renal morphology in dogs, and (b) dietary protein intake influences renal function, urine protein excretion, and renal morphology in canine renal failure. Dogs were fed a reduced protein diet for 12 weeks after induction of renal failure, while compensatory renal hypertrophy developed. Renal function was then evaluated and dogs were distributed into 2 groups with approximately equal degrees of renal dysfunction. One group was fed a high protein diet (42% protein) and a second group was fed moderately restricted protein diets (18% protein). After 8 weeks, renal function, magnitude of proteinuria, and renal morphology were re-evaluated. Inulin clearance increased in all dogs fed the 42% protein diet and 3 of 10 dogs fed the 18% protein diets. Proteinuria was significantly greater in dogs fed the high protein diet than dogs fed the reduced protein diets. Compared with previously nephrectomized contralateral control kidneys, glomerular sclerosis and renal interstitial lesions had developed in all dogs, regardless of severity of renal dysfunction or diet fed. Although reduced dietary protein intake did not prevent development of renal lesions, renal lesions were significantly more severe in the 5 dogs fed the 42% protein diet and 3 dogs fed the 18% protein diets in which inulin clearance increased, than in 7 dogs fed the reduced protein diets in which inulin clearance did not increase. PMID- 3339860 TI - Deoxyribonucleic acid ploidy and cell cycle events in benign colonic epithelium peripheral to carcinoma. AB - DNA ploidy and cell cycle phases of benign human colonic epithelium peripheral to adenocarcinoma were analyzed by flow cytometry in 188 prospective cases. Human colonic epithelium was shown to be diploid with a mean DNA index (DI) of 1.01. The G0G1 compartment accounted for nearly 93% of the cells with the remainder in the S and G2+M phases. Parallel [3H]thymidine uptake on selected cases confirmed the relatively low proliferative activity of colonic mucosa. The DNA index and the cell cycle compartments exhibited no correlation to the ploidy, Dukes' stage, size, and anatomical location of the corresponding malignant tumors. Approximately 25% of the benign samples possessed DI values outside of the diploid range (defined as the mean +/- sd). Analysis of these apparently hypo- (less than 0.92) and hyper- (greater than 1.09) diploid, histologically normal samples in terms of cell cycle kinetics and their relationship to Dukes' stage, location, distance, and the ploidy of the tumor showed no correlation. The only characteristic differentiating these "aberrant" samples from diploid benign tissue was variation in DI possibly due to differences in fluorochrome binding or accessibility to DNA. Whereas these results indicate some degree of variability in the DNA content of benign colonic epithelia, neither DI nor cell cycle kinetics appear to be affected by the presence of a malignant tumor and are not representative of either the ploidy or pathologic stage of the corresponding colonic carcinoma. PMID- 3339861 TI - Characterization of solid tumor microvasculature: a three-dimensional analysis using the polymer casting technique. AB - Using a polymer casting technique in conjunction with scanning electron microscopy, the three-dimensional characterization of tumor microvasculature as a function of age of renal adenocarcinoma in the rat kidney is undertaken. The microvasculature of the rat tumor model is compared with VX2 carcinoma in the rabbit leg muscle. Light microscopy and transmission electron microscopy on the rat tumor model are performed to correlate the features seen under scanning electron microscopy of vascular casts. The casts show marked differences between tumor and normal microvasculature. The tumor vascular architecture appears disarrayed with prevalent atypical features such as coils, ribbons, sheets, dense capillary networks, saccular dilatations, leaky and otherwise highly irregular vessels. Sprouts of new growth capillaries are seen throughout the tumor casts. Compressed vessels are present and become more pronounced in older tumors. These features are not observed in normal controls treated under identical conditions. The application of this high resolution three-dimensional casting technique to tumor studies is promising for research in basic tumor mechanics as well as in the effects of tumor vasculature on mediating radiation and chemotherapy and the fundamental mechanisms of metastasis. PMID- 3339862 TI - Nasal consonants in esophageal speech. AB - Nasalization of nasal consonants was measured using the ratio of a nasal accelerometer signal amplitude to air-borne microphone signal amplitude. Utterances produced by 3 esophageal speakers were studied. Word position (and time following air injection) of the nasal consonants was varied. Degree of nasal resonance was dependent on word position, with significantly higher values for word-final than for word-initial position. PMID- 3339864 TI - Communication breakdowns in normal and language learning-disabled children's conversation and narration. AB - The frequency and type of communication breakdowns occurring in the speech of 7 language learning-disabled children (LLD), aged 9:10-11:1 (years:months), were examined in two conditions, conversation and narration, and compared to a group of 7 normal peers matched for chronological age and 7 peers matched for mean length of communication unit in conversation. Types of communication breakdowns examined included stalls, repairs, and abandoned utterances. The LLD group incurred a significantly greater rate of communication breakdowns per communication unit in narration than conversation compared to control group differences. Mean length of communication unit was also significantly greater in narration than conversation for the LLD group compared to controls. For all groups, across both speech sample conditions, longer communication units contained more breakdowns than shorter ones. The groups did not differ in the types of breakdowns. Communication unit length and the nature of the narrative task may account for the increased dysfluencies in LLD children's speech. PMID- 3339863 TI - Acoustic and perceptual measurements of roughness influencing judgments of pitch. AB - Listeners matched the pitch of 36 clear to severely dysphonic vowels to the frequency of pure tones produced by a signal generator. Mean difference scores on pitch match correlated-.56 with jitter, -51 with jitter ratio, -.57 with spectrographic noise classifications, and -.64 with vocal roughness. Moderately to severely dysphonic vowels received significantly lower pitch match values than clear to mildly dysphonic vowels. Findings suggest that the effect of vocal roughness on pitch should be considered by the clinician who makes use of perceptual judgments. PMID- 3339865 TI - Tone in Thai alaryngeal speech. AB - The perception and production of linguistic tone was investigated in utterances spoken by Thai alaryngeal speakers. Thai is a tone language with five phonemic tones. High-quality tape recordings of five monosyllabic words produced by 2 esophageal, 1 electrolaryngeal, and 5 normal, native Thai speakers were subjected to perceptual and acoustic analysis. Results from the phonemic identification tests indicated that tones produced by alaryngeal speakers were not only perceived at much lower levels of accuracy than those produced by normal speakers, but the patterns of tonal confusions for alaryngeal speakers were also dissimilar to those for normal speakers. Results from fundamental frequency (Fo) analysis revealed that the performance deficit of alaryngeal speakers could be related to specific characteristics of their Fo contours. Findings are interpreted to highlight the importance of (a) language, (b) type of prosody, (c) form of alaryngeal speech, and (d) Fo level and direction on linguistic assessments of Fo control in alaryngeal speech. PMID- 3339866 TI - Specialized cognitive function and reading achievement in hearing-impaired adolescents. AB - This study evaluated the performance of hearing-impaired adolescents on tests of specialized cognitive functioning and explored the linkage between cognitive profile and reading achievement. Other variables noted were mathematics achievement, speech production, etiology, and age of onset of hearing loss. Subjects were 62 severely-to-profoundly hearing-impaired students between 15 and 20 years of age, 31 "high readers" and 31 "low readers." Results indicated that, for this sample, cognitive function was below average for the verbal and sequential skills associated with the left hemisphere but above average for the "visuospatial" skills associated with the right hemisphere. Reading performance proved to be highly correlated with cognitive profile, as did mathematics performance and, to a lesser extent, speech and age of onset. Ramifications for instruction are discussed--in particular, development of strategies for using the right hemispheric cognitive strengths, as identified in this sample, to help overcome the deficits in "verbosequential" processing and reading achievement traditionally associated with hearing-impaired students. PMID- 3339867 TI - Performance inventory for profound and severe loss (PIPSL). AB - This study was undertaken to develop a quantifiable and reliable self-rating inventory specifically for persons with profound and severe hearing losses. Fifty such subjects with such losses who wore hearing aids rated themselves on a scale of 0-6 (never to always) on 125 items that sampled their performance in a variety of communicative situations. Items were assigned to tentative categories that were then refined so as to achieve high internal consistency, reflected by high alpha coefficients, with a minimal number of items. Six final categories, or scales, containing a total of 58 items, emerged with alpha coefficients .86 or higher. The scales were labeled Understanding Speech With Visual Cues, Intensity, Response to Auditory Failure, Environmental Sounds, Understanding Speech With No Visual Cues, and Personal. Another 16 items that failed to fit into any scale, and did not form a scale of their own, were also included in the final inventory because they related to individual rehabilitative concerns and activities in ways not represented among the items of the six scales. PMID- 3339868 TI - Description of laryngeal pathologies by age, sex, and occupation in a treatment seeking sample. AB - The purpose of the present investigation was to describe the occurrence of laryngeal pathologies and their distribution across age, sex, and occupation in a group of persons seeking physician treatment. Data were collected on 1,262 patients seen by eight otolaryngologists from three different residential areas. The five most frequent pathologies reported were nodules, edema, polyps, laryngeal cancer, and vocal fold paralysis. For the total sample, pathologies occurred more frequently in females than in males; however, certain pathologies were more common to one sex than the other. The voice-disordered population appears to be getting older. The top five occupations associated with laryngeal pathologies were retired persons, homemakers, factory workers, unemployed, and executive/managers. Comparisons with similar investigations were made. PMID- 3339870 TI - Patterns of discourse cohesion and coherence in Alzheimer's disease. AB - Patterns of discourse--as reflected in the use of propositions, cohesion devices, and in judgments of coherence--in the speech of 6 well elderly and 6 patients with senile dementia of the Alzheimer type (SDAT) during topic-centered interviews were compared. Compared to the well elderly, SDAT patients used significantly more words and conversational turns. The interviewer also used more words and turns when interviewing SDAT patients, making those interviews more lengthy and more interactive than those of the elderly comparison group. Although significant differences in propositional form and cohesion devices were not found, a pattern of cohesion disruptions in SDAT patients was identified that appears consistent with previously noted patterns of language dissolution. Coherence judgements by four listeners showed significant differences between the two groups. The breakdowns in coherence were related to one subtype of cohesion disruption, missing element. This suggests that incoherence may result in part from a loss of the ability to take the listener's perspective in developing thematic structure during conversation. It is argued that SDAT results not only in the impairment of linguistic abilities but also in the impairment of discourse abilities that contribute to Alzheimer patients' incoherent speech. PMID- 3339869 TI - An evaluation of recent trends in preschool programming for hearing-impaired children. AB - A longitudinal study was conducted of 139 children with severe and profound hearing losses. The children were between 3 and 5 years of age at the commencement of the 4-year study. The relationship of several background and educational variables with the linguistic, academic, and social development of the children was investigated. Age, hearing loss, and intelligence were related to most of the dependent measures. Relationships involving communication mode (auditory/oral vs. total communication) varied with the measure being considered. The variable of program type (individual vs. group) interacted with the degree of hearing loss and with communication mode. Although early intervention was related to certain dependent measures, no relationships were found that involved direct instruction by parents or integration. PMID- 3339871 TI - Phonetic inventories of 2- and 3-year-old children. AB - This report provides quasi-longitudinal independent analysis data on two groups of 10 children at 2:0 (years:months), 2:5, 2:9, and 3:3. The analysis included word-initial and word-final phonetic inventories of consonant singletons and clusters and a summary of the relative frequency of seven word shapes. The results indicated that these children were gradually "filling in the gaps" with sounds previously reported to be lacking in slightly younger children. PMID- 3339872 TI - The rabbit autoperfusing heart-lung preparation. AB - The autoperfusing heart-lung preparation holds promise as a method for extended organ preservation. Further understanding of the hemodynamics, metabolism, and quality of tissue preservation of this preparation may increase the number of available organs for heart-lung transplantation. We describe the materials and operative technique for a small animal model of the autoperfusing heart-lung preparation. The method is easy to learn, the materials and animal subjects are inexpensive, and the preparation is fully monitored to provide consistent and reproducible data. The rabbit autoperfusing heart-lung preparation is an excellent vehicle for the investigator studying warm organ preservation. PMID- 3339873 TI - Increased synthesis of secreted hepatic proteins during abdominal sepsis. AB - To study the effect of intraabdominal sepsis on hepatic protein synthesis, male Sprague-Dawley rats underwent celiotomy with either cecal ligation and puncture (CLP) or sham operation. Eight and sixteen hours later total hepatic protein synthesis was measured by flooding dose technique. Specific synthetic rates of structural or secreted hepatic proteins were further studied 16 hr after CLP in an isolated perfused liver model. Total hepatic protein synthesis was significantly elevated at 16 hr (59 +/- 6%/day vs 37 +/- 6%/day, P less than 0.05), but not 8 hr post-CLP. Structural hepatic protein synthesis was unchanged after CLP; however, the synthetic rates of the acute-phase secretory proteins alpha 1-acid glycoprotein, transferrin and complement component C3 were significantly increased 16 hr after CLP. However, the albumin synthetic rate was not increased during sepsis. We conclude that sepsis causes augmentation of hepatic protein synthesis primarily to increase acute-phase proteins for host defense. PMID- 3339875 TI - Vagal release of serotonin into gut lumen and portal circulation via separate control mechanisms. AB - The mechanisms controlling vagally induced release of serotonin-like immunoreactivity (5-HTLI) into portal circulation and jejunal lumen were studied in individual cats. In control animals, electrical vagal nerve stimulation significantly enhanced both the endoluminal secretion rate of 5-HTLI and the release of 5-HTLI into the portal vein. The vagally induced release of 5-HTLI into portal circulation was blocked by pretreatment with propranolol or phenoxybenzamine, or by previous removal of the superior cervical ganglia, but was not blocked by atropine or hexamethonium. On the contrary, the luminal secretion of 5-HTLI after vagal stimulation was not blocked by adrenoceptor blocking agents or ganglionectomy, but instead was inhibited by cholinoceptor antagonists. Thus, in the same experimental animals it was shown that vagally induced release of 5-HTLI into portal circulation was mediated by adrenoceptor mechanisms, while endoluminal release of 5-HTLI was regulated via cholinoceptors. Based on indirect estimations, the apical release of 5-HT seems to be quantitatively small in comparison with the release into portal circulation. PMID- 3339874 TI - In vivo isolated liver perfusion technique in a rat hepatic metastasis model: 5 fluorouracil concentrations in tumor tissue. AB - An in vivo method of isolated rat liver perfusion was developed with true vascular isolation and recirculating perfusate. This new surgical technique to temporarily isolate the liver vascularly, and the perfusion procedure are described in depth. Twelve inbred WAG/RIJ rats were subjected to 25 min of normothermic liver perfusion without chemotherapy, and all rats survived the procedure. Hepatic functional and histological integrity were not significantly altered during perfusion. To determine the role of isolated liver perfusion (ILP) as a means of improved targeting of antitumor agents, 5-fluorouracil (5-FU) concentrations were monitored in hepatic tumor and liver tissues and in systemic plasma using high-performance liquid chromatography. Fifty-one rats with hepatic tumors of colonic origin were randomly assigned to one of three dosage groups (20, 40, or 80 mg/kg) receiving 5-FU by ILP, hepatic artery infusion (HAI), or jugular vein infusion (JVI). ILP resulted in significantly increased 5-FU concentrations in liver tissue. However, no significant differences were found in tumor tissue concentrations of 5-FU between the three treatment modalities. 5-FU concentrations in tumor tissue increased as a function of the dose with ILP, HAI, and JVI. ILP was associated with the lowest systemic drug concentrations. The low systemic 5-FU concentrations with ILP suggest a higher maximum tolerable dose. This mode of treatment deserves to be studied further in our model before conclusions can be drawn regarding its therapeutic potential. PMID- 3339876 TI - The healing of colonic anastomoses after early intraperitoneal chemotherapy: an experimental study in rats. AB - Early postoperative intraperitoneal administration of 5-fluorouracil (5-Fu) is a logical adjuvant treatment of patients with resectable colonic cancers. It is easier and less invasive than the intraportal administration of the drug. However, before applying the procedure to humans it must be demonstrated than it does not disturb the healing of recent colonic anastomoses. Colonic sutures were performed in 78 male Wistar rats. The animals then either served as controls or received intraperitoneal 5-Fu during 5 days starting on the first, third, or seventh postoperative day. No statistical difference was observed between treated and control groups when observing the incidence of anastomotic spontaneous disruptures, anastomotic healing strength, or the weight of the animals. It is concluded that early intraperitoneal 5-Fu administration does not impair the healing of recent colonic anastomoses in rats. PMID- 3339878 TI - Attitudes and experiences of fourth year medical students in a teaching nursing home project. PMID- 3339877 TI - Lymphatic smooth muscle responses to leukotrienes, histamine and platelet activating factor. AB - Regional lymphatics regulate the accumulation of edema resulting from inflammation. The effects of mediators of inflammation on lymphatic smooth muscle, the primary determinant of lymph flow, are poorly understood. We studied mesenteric lymphatic vessels in 22 anesthetized rats with in vivo videomicroscopy following topical applications of histamine, leukotriene C4 or D4, or platelet activating factor (PAF). Diameter, contractility, and contraction frequency were measured, and flow was calculated. Histamine caused increases in vessel diameter and contractility (174 and 218% of control, respectively; P less than 0.05), while contraction frequency was unaffected. Leukotrienes C4 and D4 caused an increase in frequency of contraction (348 and 392% of control, respectively; P less than 0.05), while having no significant influence on diameter or contractility. PAF caused smooth muscle relaxation, resulting in vasodilation and a decrease in contraction frequency (202 and 5% of control, respectively; P less than 0.05). Topical application of histamine and leukotrienes caused significant increases in calculated flow, while PAF decreased calculated flow. Mediators of inflammation have striking and diverse effects on lymphatic smooth muscle activity. PMID- 3339879 TI - The supply of primary care physicians in Tennessee. PMID- 3339880 TI - Listeria monocytogenes endocarditis. PMID- 3339881 TI - Professional liability--an open letter. PMID- 3339882 TI - Update on ulcer disease. PMID- 3339884 TI - Splenic abscess. PMID- 3339883 TI - Blunt hepatic vein disruption. PMID- 3339885 TI - Abnormal liver function tests in a middle-aged woman. PMID- 3339887 TI - Reported cocaine deaths rise in Tennessee. PMID- 3339886 TI - "Minor" surgery. PMID- 3339888 TI - Management of penetrating lung injuries in civilian practice. AB - Recent reports of military thoracic injuries have advocated early thoracotomy and aggressive management of pulmonary injuries with resection as opposed to the more conservative and traditional treatment with chest tube thoracostomy. A retrospective study was therefore performed to determine the incidence of thoracotomy and lung resection in civilian injuries and to evaluate the effectiveness of treatment of these injuries. Between 1973 and 1985, in a series of 1,168 patients, there were 384 gunshot wounds and 784 stab wounds to the thorax. Two hundred eighty-three patients with a gunshot wound (74%) and 602 with a stab wound (77%) were treated with chest tubes alone. Sixty-eight patients (6% of the total) required operative repair of pulmonary hilar or parenchymal injury. Pulmonary resection was necessary in only 18 patients (nine with a gunshot wound and nine with a stab wound), and 10 patients had repair of hilar injuries (nine with a gunshot wound and one with a stab wound). Of patients requiring pulmonary resection, nine required wedge or segmental resection, six required lobectomy, and three patients required pneumonectomy. Mortality for all thoracic injuries was 2.3%: for those treated with chest tube alone, 0.7%; for pulmonary hilar injuries, 30%; for pulmonary parenchymal injuries, 8.6%; and for injuries necessitating lung resection, 28%. Most civilian lung injuries can be treated by tube thoracostomy alone. Although relatively few patients with primary pulmonary injury require thoracotomy, those that do are at significant risk and may require lung resection to control bleeding or hemoptysis or to remove destroyed or devitalized lung tissue. PMID- 3339889 TI - In vivo evaluations of a new thromboresistant polyurethane for artificial heart blood pumps. AB - To reduce the risk of thromboembolic complications in prosthetic blood pumps, we have developed a new segmented polyurethane elastomer. This material is unique because its mechanical properties for long-term durability and surface properties for biocompatibility have been separated and developed in two distinct materials. Improved thromboresistance is then obtained by a 1% concentration of a new polymeric surface-modifying additive blended with the base polyurethane before fabrication of the blood pump. To evaluate this material in vivo, we performed 10 implants, in calves, of the Pierce-Donachy prosthetic ventricle with blood pumping sacs and cannulas fabricated from the new surface-modifying additive copolymer blend (Thoratec's BPS-215M). In four control implants the blood sacs and cannulas were fabricated from Ethicon's Biomer segmented polyurethane, which is the present clinical standard for most artificial hearts and circulatory support devices. The blood pumps were connected from the apex of the left ventricle to the descending aorta in male Holstein calves weighing 82 to 108 kg and were driven pneumatically in the full-to-empty mode with flows averaging 5 to 6 L/min. Each calf was medicated with aspirin and dipyridamole throughout the study period and was electively put to death after 4 weeks for evaluation of explanted blood sacs and for examination of the kidneys for infarction. All 10 explanted blood sacs made with the surface-modifying additive copolymer blend were shiny and completely free of thrombus. Three of the four explanted Biomer blood sacs showed visible red thrombus, and all four showed small areas of white thrombus. The average surface area of the Biomer blood sacs covered with thrombus was 45 +/- 32 mm2. Use of a semiquantitative scale to assess renal infarction demonstrated that nine of 10 animals with a surface-modifying additive copolymer blend blood sac had infarction less severe than the mean infarct score of the animals with a Biomer sac. The surface-modifying additive copolymer blend has excellent mechanical and physical properties necessary for use in artificial heart blood pumps. From these experiments, we conclude that the surface-modified polyurethane blend is superior to Biomer polyurethane in blood compatibility and in freedom from thromboembolic risk. This material is now approved by the Food and Drug Administration for investigational device exemption studies in the Pierce-Donachy prosthetic ventricle. PMID- 3339890 TI - Early results for anatomic correction of transposition of the great arteries and for double-outlet right ventricle with subpulmonary ventricular septal defect. AB - Fifty patients, 21 with transposition of the great arteries plus ventricular septal defect, four with double-outlet right ventricle plus ventricular septal defect, and 25 with transposition of the great arteries plus intact ventricular septum, have undergone anatomic correction. There were four hospital deaths, all in the patients with ventricular septal defects (overall mortality rate 8%). The Lecompte maneuver was used in all patients, and in the last 25 patients the coronary arteries were transposed to medially hinged trapdoor flaps created in the neoaorta. In 10 patients (20%) intraoperative adjustments were necessary to the great vessels and coronary arteries to achieve unobstructed coronary artery flow. There have been no late deaths. Postoperative cardiac catheterization in 19 patients has revealed stenosis on the new main pulmonary artery suture line to be the main early problem. Anatomic correction of transposition (with or without ventricular septal defect) and double-outlet right ventricle septal defect would seem to be a good operative alternative to the Mustard or Senning operation, with the advantage of incorporating the left ventricle into the systemic circulation. PMID- 3339891 TI - Ischemic myocardial protection. Comparison of nonoxygenated crystalloid, oxygenated crystalloid, and oxygenated fluorocarbon cardioplegic solutions. AB - This study was designed to compare myocardial protection with a nonoxygenated crystalloid solution, an oxygenated crystalloid solution, and an oxygenated fluorocarbon cardioplegic solution. Postischemic ventricular performance was studied in three equal (N = 7) groups of dogs subjected to 120 minutes of global ischemia induced at an average myocardial temperature of 18.5 degrees +/- 1.4 degrees C (range 17.0 degrees to 21.0 degrees C). Left ventricular global and regional function was evaluated by sonomicrometry and micromanometers before ischemia and at 45 and 60 minutes after ischemia. Stroke volume index, left ventricular pressure-minor external diameter loop area, percent shortening, first derivative of left ventricular pressure, mean velocity of circumferential fiber shortening, and the slope of the end-systolic pressure were used to evaluate myocardial contractility. In vitro oxygen content of the three cardioplegic solutions was measured at a mean injection temperature of 8.3 degrees +/- 0.6 degrees C: 0.8 +/- 0.1 vol% (nonoxygenated crystalloid cardioplegia), 3.2 +/- 0.2 vol% (oxygenated crystalloid cardioplegia), and 6.2 +/- 0.2 vol% (oxygenated fluorocarbon cardioplegia). Recovery of global and regional function was significantly (p less than 0.05) better with both oxygenated solutions than with the nonoxygenated solution. Differences between the oxygenated crystalloid and fluorocarbon groups were not significant. We conclude: (1) Compared to nonoxygenated crystalloid cardioplegia, oxygenated crystalloid and oxygenated fluorocarbon cardioplegic solutions gave superior myocardial protection during 2 hours of ischemic arrest; (2) no difference was found in protective effects between an oxygenated crystalloid and an oxygenated fluorocarbon solution. PMID- 3339892 TI - Subaortic stenosis and sudden death. AB - An obese white boy, 16 years old, collapsed and suddenly died while walking with friends. Since early childhood he had been known to have mild subaortic stenosis. At age 6 he exhibited first-degree heart block during an electrocardiographic exercise test. Neither then nor thereafter was he known to have any unusual symptoms until his death. Postmortem examination revealed marked cardiac enlargement without asymmetry or much dilatation. There was mild subaortic stenosis, but the heart was otherwise grossly normal. Special studies of his cardiac conduction system demonstrated fibrotic obliteration of the His bundle and proximal portions of both bundle branches. The same region had a much thickened central fibrous body from which the subaortic stenosis ridge protruded. Small arteries in the vicinity of the atrioventricular node were markedly narrowed. Because those vessels provide some of the blood supply to the His bundle region, their narrowing may have contributed to the fibrotic abnormalities observed. The extent of destruction of the His bundle makes a lethal failure of atrioventricular conduction the most likely terminal event. PMID- 3339893 TI - A new intraoperative approach for endocardial mapping of ventricular tachycardia. AB - Results of operation for control of ventricular tachycardia have improved since endocardial mapping techniques have been developed that allow a directed approach to the problem. In some patients, a limitation of established techniques has been difficulty in initiating the arrhythmia after a ventriculotomy has been made to allow introduction of endocardial recording electrodes. This paper describes a transatrial approach for endocardial mapping with a balloon array of 112 electrodes, which has been used intraoperatively in 15 patients. Surgical success in this group has been compared to that obtained in a similar group of patients in whom standard techniques of intraoperative mapping were used. With our new balloon technique we have been able to easily induce and map multiple episodes of ventricular tachycardia in all cases. On the basis of detailed endocardial maps, the locations of earliest activation and possible reentry loops have been identified and ablated with either endocardial excision or application of the cryoprobe. When indicated, concomitant procedures including aneurysm resection (9/15) and bypass grafting (14/15) have been performed. Hospital mortality in this group was 20%. None of the deaths have been related to recurrent ventricular tachycardia or complications of the mapping technique. Postoperative electrophysiologic studies performed at 2 weeks have been normal in 11 of 12 or 92% of patients. To date (mean follow-up 12 +/- 6 months) there has been no clinical recurrence or evidence of ventricular tachycardia by Holter monitoring in these patients. We conclude that the transatrial balloon approach to endocardial mapping facilitates intraoperative induction of ventricular tachycardia, allows complete mapping during multiple runs of the arrhythmia without prolonging cardiopulmonary bypass time, and improves results of operation using standard ablation techniques. PMID- 3339894 TI - Esophageal manometric studies in patients with myasthenia gravis. AB - Dysphagia is often present early, with varying degrees of involvement, in patients with myasthenia gravis. Twenty-five patients with a clinical status of myasthenia gravis were graded according to a modified Osserman classification and the esophageal manometric results were reported according to their clinical status. The results were also compared with those in 20 normal control subjects. Twenty-four patients (96%) had abnormal motility. The only patient who was in class I had a normal tracing. There was no significant difference in function of the lower esophageal sphincter, but a significant decrease in mean amplitude (15.1 +/- 6.1 versus 29.7 +/- 4.7 mm Hg) and a prolongation in mean duration of the peristaltic wave (7.4 +/- 2.8 versus 4.5 +/- 0.2 seconds) was noted in the upper esophagus. The cricopharyngeal sphincter pressure also showed a significant decrease (23.4 +/- 9.5 versus 43.1 +/- 3.1 mm Hg), but relaxation and coordination were good. The mean amplitudes, mean duration of peristaltic waves, and cricopharyngeal pressures between the myasthenic and control populations were statistically significant, with a p value of 0.001. Besides this, frequent spontaneous contractions, simultaneous contractions, and biphasic repetitive contractions typical of peristaltic dysfunction were also found in myasthenic patients. Motor dysfunction of the esophagus as assessed by manometric study correlates well with Osserman's modified clinical classification. PMID- 3339895 TI - The acute effects of AICAR on purine nucleotide metabolism and postischemic cardiac function. AB - The purine precursor AICAR (5-amino-4-imidazolecarboxamide) has been advocated as a substrate for myocardial adenine nucleotide repletion during postischemic reperfusion. The purpose of this study was to investigate the acute effects of this agent on adenine nucleotides, inosine monophosphate, and postischemic ventricular function in an isolated rat heart preparation. The hearts were perfused at constant flow, either continuously for 90 minutes or for a 30 minute period followed by 10 minutes of global normothermic (37 degrees C) ischemia. The ischemic hearts were then reperfused for 15, 30, and 60 minutes. Both groups were treated with AICAR in a concentration of 100 mumol/L throughout the perfusion protocols. In the nonischemic time control group there was no effect on the levels of adenosine nucleotides or developed pressure over 90 minutes of perfusion. In contrast, AICAR treatment increased tissue inosine monophosphate content four-fold and sevenfold at 60 and 90 minutes, respectively (p less than 0.05), but had no effect on tissue adenosine monophosphate levels. During ischemia, there was a 50% decrease in adenosine triphosphate content in the AICAR treated hearts and a thirteen-fold increase in adenosine monophosphate levels (p less than 0.05). After 60 minutes of reperfusion, adenosine triphosphate and monophosphate levels in the AICAR-treated hearts recovered to only 52% and 59% of preischemic values, respectively. These findings were similar to those observed in the untreated ischemic hearts. In contrast, tissue inosine monophosphate content in the AICAR-treated hearts during reperfusion remained significantly elevated and was fivefold greater than the reperfusion values in the untreated group. Concurrently, AICAR failed to enhance the recovery of postischemic left ventricular developed pressure. These results suggest that inhibition of the conversion of inosine monophosphate to adenosine monophosphate limits the usefulness of the agent in evaluating the temporal relationships between postischemic adenosine triphosphate repletion and recovery of myocardial function in the acute setting. PMID- 3339896 TI - Parasternal mediastinoscopy. Assessment of operability in left upper lobe lung cancer: a prospective analysis. AB - Between 1976 and 1984, 242 patients with presumably operable lung cancer were treated surgically. In the Canisius Wilhelmina Hospital, Nijmegen, The Netherlands, in the period 1976 to 1980, 109 of 131 (83.2%) patients underwent cervical mediastinoscopy to assess operability. They were studied retrospectively. During this examination, lymph node metastasis was demonstrated in three of 19 (15.8%) patients with left upper lobe lung cancer. At thoracotomy after a normal cervical mediastinoscopic study or no mediastinoscopic study, periaortic lymph node metastases were found in eight of 34 (23.5%) patients with left upper lobe lung cancer. In the period 1981 to 1984, the value of left parasternal mediastinoscopy was studied prospectively in patients with left lung cancer in the Canisius Wilhelmina Hospital, Nijmegen; in the Lung Centre of the Radboud University Hospital, Nijmegen; and in the Lung Center of the Dekkerswald Medical Centre, Groesbeek. Cervical or cervical and parasternal mediastinoscopy were performed in 69 of 111 (62.2%) patients. At parasternal mediastinoscopy performed after a normal cervical mediastinoscopic study, periaortic lymph node metastases were found in seven of 31 (22.6%) patients with left upper lobe lung cancer. All periaortic lymph node metastases showed intranodal and extranodal growth. The resectability rate in left upper lobe lung cancer was 79.4% in the retrospective group and 96.5% in the prospective group. There were no serious complications after parasternal mediastinoscopy. These data point to the reliability of parasternal mediastinoscopy in the assessment of left upper lobe lung cancer. The study provides essential information for the staging and treatment of non-small cell lung cancer of the left upper lobe. PMID- 3339897 TI - Operative strategy in combined coronary and carotid artery disease. AB - In the period between the opening of our heart center in November 1984 and May 1986, 2001 cardiac operations were performed with the aid of cardiopulmonary bypass. Almost three quarters (73.5%, n = 1471) of the patients had coronary artery disease and 20% (n = 359) had acquired valvular heart disease. In 47 of 1471 patients who underwent coronary artery bypass grafting, a simultaneous carotid endarterectomy was performed. They included 36 men and 11 women, aged between 51 and 78 years (mean 64 years). Preoperatively, 12 patients had cerebrovascular symptoms and 35 were neurologically asymptomatic. Twenty-three had unilateral carotid stenosis and 24 had bilateral or multiple vessel disease of the extracranial arteries. All except four patients had triple-vessel coronary artery disease. In three patients with aortic valve disease, coronary bypass, carotid endarterectomy, and aortic valve replacement were performed simultaneously. Cardiopulmonary bypass was instituted before carotid endarterectomy was performed, with mild hypothermia and hemodilution for added protection. Electroencephalographic monitoring was used throughout the operation. Forty-six of the 47 patients survived the operation without neurologic or cardiac complications. One patient had a neurologic deficit with hemiplegia and coma, which was lethal. We conclude that simultaneous endarterectomy of significant extracranial artery stenosis in candidates for coronary bypass is a method safe enough to justify its routine use. PMID- 3339898 TI - Oxygen requirements of the isolated rat heart during hypothermic cardioplegia. Effect of oxygenation on metabolic and functional recovery after five hours of arrest. AB - Previous studies from this laboratory demonstrated that the use of an oxygenated cardioplegic solution in the hypothermic arrested rat heart resulted in improved preservation of high-energy phosphate stores (adenosine triphosphate and creatine phosphate), mechanical recovery during reperfusion, and preservation of myocardial ultrastructure. In the current study the effect of cardioplegic solutions oxygenated with 30%, 60%, and 95% oxygen was evaluated in the isolated rat heart with reference to the maintenance of adenosine triphosphate, creatine phosphate, oxygen consumption, functional recovery, and mitochondrial oxidative phosphorylation in vitro. Results indicate that the hearts receiving cardioplegic solutions supplemented with 95% oxygen and 5% carbon dioxide maintained adenosine triphosphate and creatine phosphate at control values for at least 5 hours. The oxygen consumption during elective cardiac arrest, mechanical performance during reperfusion, and in vitro mitochondrial oxygen uptake and phosphorylation rate were highest in the hearts receiving cardioplegic solutions supplemented with 95% oxygen when compared to solutions with 30% and 60% oxygen. Addition of glucose and insulin to the cardioplegic solution (95% oxygen) increased the adenosine triphosphate levels but failed to improve function after reperfusion. Although myocardial adenosine triphosphate and creatine phosphate were well preserved by the oxygenated cardioplegic solution, there was a discrepancy between the adenosine triphosphate levels at the end of the arrest period, which represents the potential for mechanical function, and the actual function of the hearts after 5 hours. PMID- 3339899 TI - Long-term clinical results after mitral valve replacement with the Bjork-Shiley prosthesis. AB - The experience of 810 mitral valve replacements performed during a 15-year period (1969 to June 1983) is reported. All but one patient received a Bjork-Shiley disc valve. Five different Bjork-Shiley models were used (Delrin, n = 51; standard pyrolytic carbon, n = 307; convexo-concave with an opening angle of 60 degrees, n = 229; convexo-concave with an opening angle of 70 degrees, n = 123; and the Monostrut valve, n = 99). The follow-up was 99.8% complete and covered 4614 patient-years (mean 6.0 years). An autopsy was performed in 77% of all fatalities. Early mortality was 5.7% and decreased during the study period. The 5 , 10-, and 15-year actuarial survival rates (early mortality excluded) were 78%, 62%, and 51%, respectively, and the complication-free survival rates at the same time intervals were 67%, 51%, and 36%. Seven percent of early deaths and 25% of late deaths were valve related, and most of these were due to valve thrombosis. The incidence of valve thrombosis was significantly (p less than 0.0005) reduced after the introduction of the convexo-concave valves, and this reduction was achieved without any increase in bleeding complications. The only patient-related factor found to be related to postoperative thromboembolism was a history of preoperative embolism (p less than 0.05). Most events occurring after implant (death, embolism, valve thrombosis, reoperation, and valve failure) had a peak incidence during the first postoperative year, whereas anticoagulant-related bleedings occurred at a constant rate of 1.2/100 patient-years. The linearized incidence of embolism was 1.6/100 patient-years (actuarial incidence at 5 and 10 years 6.9% and 13.0%, respectively). Seven strut fractures occurred (0.2/100 patient-years, actuarial incidence at 5 and 10 years 1.1%), as did five instances of prosthetic valve endocarditis (0.1/100 patient-years, actuarial incidence at 5 and 10 years, 0.7% and 1.3%). A new concept of valve failure is presented and includes a distinction between events related to the surgical procedure (treatment failure; 1.9/100 patient-years, actuarial incidence at 5 and 10 years 11.0% and 13.5%) and events possibly related to the prosthesis (prosthetic failure; 1.1/100 patient-years, actuarial incidence at 5 and 10 years 7.0% and 8.0%). PMID- 3339900 TI - Life-threatening complications of cardiac operations and occurrence of myocardial catecholamine bombs. AB - Myocardial catecholamine bombs (huge local intra-axonal accumulations of catecholamine, mainly norepinephrine, within cardiac tissue) were observed in (right auricular) myocardial biopsy specimens in 16 of 65 adult patients selected randomly from a series of elective cardiac operations. The occurrence of catecholamine bombs was in highly significant correlation (p less than 0.001) with the occurrence of life-threatening complications of cardiac operations (life threatening arrhythmias [ventricular tachycardias, ventricular fibrillation, asystole], clinically evident perioperative myocardial infarction/postoperative low-output syndrome, death). There was a very close correlation between the occurrence of catecholamine bombs and life-threatening arrhythmias. Life threatening arrhythmias occurred in 13 patients. Eight of them belonged to the group of 16 patients with catecholamine bombs and five belonged to the group of 49 patients with no bombs; the difference (8/16 versus 5/49) is very clear (p less than 0.001). It was our experience that dangerous arrhythmias related to catecholamine bombs may occur as late as during the second postoperative week. We believe our observations are of considerable clinical importance, because catecholamine bombs are easily identified by fluorescence microscopic examination of right auricular myocardial specimens retrieved intraoperatively, and patients at high risk can then be selected (during the operation) for more extensive and prolonged surveillance and possibly prophylactic treatment. PMID- 3339902 TI - Laser endarterectomy and angioplasty: a cautionary note. PMID- 3339901 TI - Evaluation of long-term results of bicuspidalization annuloplasty for functional tricuspid regurgitation. A seventeen-year experience with 133 consecutive patients. AB - Between 1968 and 1985, 133 consecutive patients underwent bicuspidalization annuloplasty for moderate to severe functional tricuspid regurgitation associated with mitral or combined mitral and aortic valve disease. Over this period, the incidence of tricuspid valve replacement was only 2.3% (3/136 patients). There were 18 early deaths (13.5%) in the entire series--three (5.0%) of 60 patients in the last 5 years of the study--and 10 late deaths (8.7%). Actuarial survival rate for the entire series, excluding early deaths, was 91.0% +/- 3.0% at 10 and 17 years. There were seven reoperations (6.1%) on the tricuspid valve, needed because of residual or recurrent mitral valve lesions after the initial operation. Actuarial rates of freedom from reoperation on the tricuspid valve were 93.6% +/- 3.0% (10 years) and 69.7% +/- 16% (17 years) for the entire series: 78% +/- 10% (15 years) for the open mitral commissurotomy plus tricuspid annuloplasty group (44 patients); 90% +/- 9.0% (15 years) for the mitral plus tricuspid annuloplasty group (10); 75.2% +/- 22% (17 years) for the mitral replacement plus tricuspid annuloplasty group (58); and 92.6% +/- 7.0% (16 years) for the combined aortic and mitral valve surgery plus tricuspid annuloplasty group (21). Ninety-eight percent of the survivors were in New York Heart Association class I or II postoperatively. Of 21 randomly selected patients investigated by pulsed Doppler echocardiography, 14 (67%) had no regurgitation or grade 1/4 tricuspid regurgitation and the remaining seven (33%) had grade 2/4 regurgitation postoperatively. Our experiences suggest that bicuspidalization annuloplasty can be a reliable method in the vast majority of patients with functional tricuspid regurgitation. PMID- 3339903 TI - Immunological and molecular studies in a case of follicular lymphoma with an extra chromosome 12 and t(2;8) translocation. AB - Two sequential lymph node biopsies taken from a non-Hodgkin lymphoma patient revealed two karyotype abnormalities peculiar to B cell neoplasias: trisomy 12 and t(2;8)(p12;q24) translocation. The first was documented in all cells analyzed, while the second was present in 20% of the metaphases from the first biopsy and in 100% from the second. This suggests that the t(2;8) translocation arose as a secondary karyotypic change. In addition, although immunological characterization of the neoplastic cells disclosed a monoclonal B cell population that expressed immunoglobulin kappa light chains, as usually found in Burkitt's lymphoma with t(2;8) translocation, Southern blot analysis provided evidence of rearrangement in only one kappa chain allele. PMID- 3339904 TI - Stage D1 prostatic adenocarcinoma: significance of nuclear DNA ploidy patterns studied by flow cytometry. AB - Flow cytometric analysis of nuclear DNA ploidy pattern was performed on 91 samples of prostatic adenocarcinoma from patients with stage D1 disease (metastatic deposits in pelvic lymph nodes). All patients had undergone radical retropubic prostatectomy and bilateral pelvic lymphadenectomy. Clinical follow-up ranged from 5 to 19 years. Nuclei were extracted from paraffin-embedded archival material. Isolated nuclei were stained with propidium iodide. The DNA ploidy pattern was diploid (normal) in 42% of tumors, tetraploid in 45%, and distinctly aneuploid in 13%. Only 15% of DNA diploid tumors progressed locally or systemically, whereas 75% of tumors with an abnormal DNA ploidy pattern (tetraploid or aneuploid) subsequently progressed (P less than 0.0001). Among low grade tumors, ploidy analysis detected a subgroup associated with a poor prognosis; among high-grade tumors, a subgroup associated with a favorable prognosis was detected. None of the patients with a DNA diploid tumor died of prostatic cancer during the period of observation. In contrast, 43% of patients with DNA tetraploid tumors and 44% of those with DNA aneuploid tumors had died of prostatic cancer 10 years after surgical treatment (P less than 0.001). Determination of nuclear DNA ploidy pattern by flow cytometry provides objective, highly significant, prognostic information for patients with stage D1 prostatic carcinoma. PMID- 3339905 TI - Frequency and significance of immunoglobulin M antibody to hepatitis B core antigen in corticosteroid-treated severe chronic active hepatitis B. AB - To assess the frequency and significance of immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc) in corticosteroid-treated severe chronic active hepatitis B, we tested 96 serum samples from 16 patients who were seropositive for hepatitis B surface antigen (HBsAg) (group 1) and 8 HBsAg negative, anti-HBc-positive patients (group 2) by enzyme-linked immunoassay. Samples obtained in the presence and absence of disease activity before, during, and after long-term corticosteroid therapy (mean duration, 42 +/- 7 months) were evaluated. Seropositivity for IgM antibody was demonstrated in 12 group 1 patients, including 9 tested before corticosteroid therapy; no group 2 patients were seropositive. Seropositivity was more common in serum samples obtained during active than during inactive disease (51% versus 22%; P less than 0.05) and more frequent in serum samples that contained hepatitis B e antigen (46% versus 11%; P less than 0.02) and hepatitis B virus deoxyribonucleic acid (50% versus 24%; P less than 0.05) than in those without these markers. In some patients, seropositivity persisted or recurred intermittently during corticosteroid therapy for up to 57 months. We conclude that seropositivity for IgM antibody can be demonstrated frequently by enzyme-linked immunoassay in corticosteroid-treated patients with severe disease. Seropositivity reflects active virus replication, and it is commonly associated with inflammatory activity. The duration of seropositivity may be protracted during long-term corticosteroid therapy. PMID- 3339906 TI - Cancer after exposure to metronidazole. AB - We assessed the risk of occurrence of cancer associated with exposure to metronidazole in the 771 female residents of Rochester, Minnesota, who were treated with metronidazole for vaginal trichomoniasis during the period 1960 through 1969 and were followed up for a total of 12,628 person-years. Standardized morbidity and mortality ratios were determined by using an expected number calculated by applying age-specific incidence rates from Rochester studies and Cancer Surveillance, Epidemiology, and End-Results Reporting (SEER) data to the person-years of follow-up. The overall standardized morbidity ratios for cancer at all sites were 1.4 (Rochester, 1978 through 1983), 1.5 (SEER data for Iowa, 1978 through 1981), and 1.2 (SEER data for Connecticut, 1978 through 1981). By site of the cancers, the standardized morbidity ratios greater than unity were those for malignant lesions of the lung, breast, thyroid, bladder, brain, kidney, nasopharynx, and oral cavity, as well as for multiple myeloma and malignant melanoma; however, the only significantly elevated standardized morbidity ratio was that for bronchogenic carcinoma. After adjustment for smoking status, the standardized morbidity ratio for bronchogenic cancer was 2.5 (95% confidence interval of 1.3 to 4.4). The standardized mortality ratio for cancer at all sites was 1.4 (95% confidence interval of 0.9 to 2.2). The analysis of these data suggests no significant increase in cancer-related morbidity or mortality for women exposed to metronidazole for treatment of vaginal trichomoniasis. PMID- 3339908 TI - The aging heart. PMID- 3339907 TI - Cortical and cancellous bone: age-related changes in morphologic features, fluid spaces, and calcium homeostasis in dogs. AB - The changes in cortical and cancellous bone that occur with aging were studied by measuring morphologic and physiologic variables for both types of bone in dogs. The percentage area of cortical and cancellous bone, rate of bone formation, vascular volume, bone water, and volume of distribution of calcium tracer all showed statistically significant changes at the time of bone maturity. Canine cortical bone cell volume progressively decreased with advancing age, and cancellous bone cell volume significantly decreased between adult and old dogs. The volume of distribution technique can be used to determine the relative contributions of cortical and cancellous bone to the total body exchangeable calcium ion pool. PMID- 3339909 TI - Laurence-Moon syndrome? PMID- 3339910 TI - Amiodarone-related optic neuropathy. PMID- 3339911 TI - Antimicrobial agents. PMID- 3339912 TI - Prescription drug use in 1984 and changes over time. AB - More than 1.5 billion prescriptions were dispensed from retail pharmacies in 1984 at a consumer cost of +18.4 billion. The number of prescriptions dispensed in 1984 equaled the previous record set in 1973. Over 40% of 1984 prescriptions were for four therapeutic classes: cardiovascular drugs, anti-infectives, psychotherapeutic drugs, and diuretics. Prescriptions for cardiovascular drugs and diuretics increased substantially from 1975 to 1984, while prescriptions for psychotherapeutic drugs decreased. Outpatient use of systemic antiinfectives remained fairly stable over the 10-year period. Trends in the use of specific drug categories within these broad therapeutic classes were variable, as were patient age and sex distributions. PMID- 3339913 TI - Conceptualizing the utilization of ambulatory medical care as a process. AB - There are two conceptual problems with the study of the utilization of ambulatory care: 1) a problem of definition and 2) a problem of measurement. Large multivariate studies conceptualize utilization in a straightforward and static manner that is reflected in the way they measure utilization: as a sum of the number of visits to physicians over a period of time. However, utilization can be construed as a process occurring through time. The object of an analysis of utilization is to examine the causes of the changes in the levels of utilization patients undergo from one period to the next. In this paper, a Markovian model for studying utilization as a process is set up, using data on utilization from a sample of 2,149 patients from Montreal (1981). Results show that the effect of age and sex on utilization is not structured in the same way when using a Markovian model as when using a traditional model, where utilization is measured by the number of visits in one period. Thus, the results of large multivariate studies are most probably biased. PMID- 3339914 TI - Hospital selection into multihospital systems. The effects of market, management, and mission. AB - The growing literature on multihospital systems (MHS) has concentrated on assessing system performance without a concurrent examination of the assumptions related to the conditions under which hospitals and systems affiliate with each other. Using a net present-value framework the current study develops and tests a model that explains the entry patterns of hospitals into multihospital systems. Specifically, we assess the role of the hospital's market, management activity, and mission compatibility with the system as predisposing conditions of MHS affiliation. The model is tested on a sample of 306 affiliated and 918 nonaffiliated hospitals under conditions of market equilibrium and disequilibrium, and for hospital entry into both non-profit and investor-owned multihospital systems. Results suggest that the relative impact of market factors, hospital management characteristics, and mission compatibility on MHS entry will vary systematically as a function of assumptions about the hospital's market and the type of system with which the hospital affiliates. PMID- 3339915 TI - Comparing the quality of death for hospice and non-hospice cancer patients. AB - In this secondary analysis of data from the National Hospice Study (NHS), a new measure, quality of death (QOD), was developed by weighting reports of cancer patients' last 3 days of life by what patients wanted their last 3 days to be like. Using analysis of covariance, the QOD scores were higher for terminally ill patients in hospices (either home-care [HC] or hospital-based [HB]) than similar patients who received conventional care (CC). The results are discussed in terms of verification of the hospice philosophy and other uses for a quality of death measure. PMID- 3339916 TI - The use of ambulatory services by persons with and without phobia. AB - The delivery of ambulatory mental health and general health services to persons with phobias (unweighted n = 1,689) and without phobias during a 6-month period are examined. The phobics were part of a larger study of 18,572 subjects, drawn as a representative sample of the population in five locations, as part of the Epidemiologic Catchment Area Program (ECA). Among phobic conditions, agoraphobia most often leads to use of services related to emotional problems, especially in the specialty mental health sector. There were no significant differences between male and female subjects in their use of the various sectors for a mental health reason. The highest age group of agoraphobics that used health services most often was 25-44 years old, and the group that used them least often was 65 years and older. Agoraphobics with four or more symptoms of panic use services in higher proportions than agoraphobics with zero to three panic symptoms. The authors observe that a very large proportion of phobics report seeking no help from any source. PMID- 3339917 TI - Evaluating the effectiveness of a telephone medicine curriculum. PMID- 3339918 TI - Usefulness of selectively ordered preoperative tests. AB - The authors prospectively evaluated the usefulness of 12 preoperative tests (including blood type and screen) ordered selectively according to clinical status and importance of scheduled surgery. Two methods of assessing usefulness of tests were used, taking into account not simply their abnormality yield, but also their impact on patient care during the entire hospitalization: first, usefulness was assessed by anesthetists involved in care; second, usefulness was assessed by an automated analysis of specific clinical situations in which tests were a priori considered useful. In 3,866 patients 15,920 tests were performed; 30% of performed tests were abnormal. As a consequence of test results, surgery was delayed or cancelled in 19 patients and modified in 1, and a treatment was instituted or anesthetic management influenced in 347 (9%). Blood component therapy was instituted in 652 patients (17%). Anesthetists and automated analysis found at least one preoperative test useful in 931 patients (24%) and 890 patients (23%), respectively, whereas on a per-test basis 17% and 9% of tests were found useful. The discrepancy in usefulness assessment was mainly due to differences in evaluation of the usefulness of normal results. This study shows that the usefulness of selectively ordered preoperative tests may be high, but better criteria for their indications are needed, because tests other than those recommended by protocol were found useful. PMID- 3339919 TI - Cardiovascular pharmacotherapy I: Anti-ischemic drugs. PMID- 3339920 TI - Jugular bulb position and shape are unrelated to temporal bone pneumatization. AB - The position and shape of the jugular bulb are undependable, and thus can add difficulty to temporal bone surgery. The present study addresses the hypothesis that position and shape of the jugular bulb correlate with the extent of temporal bone pneumatization. Systematic study was done in 25 unilateral cadaver specimens. Pneumatization was determined using both the classic Runstrom II radiograph, and computed tomography. Jugular bulb shape and position were determined by anatomic dissection and computed tomography. No association of jugular bulb shape or position, with pneumatization, was found. However, the dissection-determined distance from the plane of the lateral semicircular canal to the roof of the jugular bulb (2 to 15 mm), had a good correlation (r = 0.70, p less than .001) with the distance from the internal auditory canal to the apex of the jugular bulb (1.5 to 15.0 mm). PMID- 3339922 TI - Panendoscopy in screening for synchronous primary malignancies. AB - The entire upper aerodigestive tract must be evaluated at the time of initial tumor evaluation in patients with squamous cell carcinoma of the head and neck. The necessity of panendoscopy (laryngoscopy, bronchoscopy, esophagoscopy) in this evaluation has not been demonstrated convincingly. Between January 1, 1984 and December 31, 1985, 208 patients with previously untreated squamous cell carcinoma of the head and neck were analyzed prospectively. These patients underwent head and neck examination, chest radiograph, barium esophagram, and panendoscopy. Fifteen (7.2%) had synchronous malignancies of the upper aerodigestive tract. In four patients (1.9%) the synchronous primary tumor was found only by endoscopy. Three patients (1.4%) had cancers of the hypopharynx. One patient (0.5%) had a bronchial cancer detected only on bronchoscopy. No tumors were detected by esophagoscopy that were not also seen on barium esophagram. We conclude that endoscopic examination of the hypopharynx is very helpful in screening for additional tumors in head and neck cancer patients, but routine esophagoscopy cannot be supported. Screening bronchoscopy cannot be strongly supported due to its very low yield. PMID- 3339921 TI - Vertigo in the pediatric and adolescent age group. AB - Since episodic vertigo in the pediatric and adolescent age group is unusual and therefore not well known to most otolaryngologists, we present six cases to show some of the various presentations and different underlying causes. These cases covered a wide diagnostic spectrum: meningioma, medulloblastoma, childhood migraine with vestibular symptoms, childhood Meniere's syndrome (one case due to perilymph fistula), and benign paroxysmal vertigo of childhood. The two patients with tumor and the patient with perilymph fistula were treated surgically; the other patients are being managed conservatively since these childhood conditions usually tend to diminish with time. PMID- 3339923 TI - A review of 925 cases of tympanoplasty using formaldehyde-formed-fascia grafts. AB - In this review of 925 cases of total and anterior perforations of the tympanic membrane reconstructed through the use of formaldehyde-formed-fascia (3-F) grafts, the postoperative nonperforation rate is 97.6%; blunting and/or lateralization of the graft was avoided in 93.5% of cases. Closure of the postoperative air-bone gap within 20 dB was achieved in 70% of cases. This update of a previously reported paper reinforces our opinion that the 3-F graft is an effective tool for the closure of tympanic membrane perforation with or without ossicular chain reconstruction. PMID- 3339924 TI - Anatomic reconstruction and functional rehabilitation of oromandibular defects with rigid internal fixation. AB - Fifteen consecutive patients undergoing extensive surgery for head and neck cancer involving the oral cavity and oropharynx were reconstructed using the technique of rigid internal fixation combined with various vascularized flaps. The follow-up ranged from 6 to 18 months. Modifications in various myocutaneous or vascularized free flaps combined with an analysis of the radiation physics necessary to make this procedure a viable alternative for immediate and delayed mandibular reconstruction will be discussed. Consistently satisfactory functional and cosmetic results have been achieved. PMID- 3339925 TI - Migraine equivalent as a cause of episodic vertigo. AB - There are many transient neurologic disturbances associated with various types of migraine. Visual symptoms, such as scintillating scotomata are most common, but somatosensory, motor, cranial nerve, and brain stem symptoms also occur. Among the brain stem symptoms, vestibular manifestations are quite common and include nonspecific dizziness, disequilibrium, vertigo, and motion intolerance. Auditory symptoms are less common. These transient neurologic symptoms can precede the headache as an aura, can occur during the headache, or, uncommonly, can immediately follow the headache. It is also well documented that the neurologic symptoms can occur in the period between headaches, a situation termed "migraine equivalent." Migraine equivalents usually occur in patients who have experienced typical migraine headaches earlier in life or who have migraine headaches at times other than when they experience equivalent symptoms. Rarely, typical migraine equivalent symptoms precede the development of the headaches by months or years, or occur in individuals who never develop headaches. Five patients with migraine equivalent symptoms that include vertigo are presented. The vertigo was the dominant symptom in some cases and was accompanied by nausea and vomiting. Differentiation from peripheral labyrinthine disorders is difficult, but a personal or family history of migraine, the temporal association of the neuro otologic symptoms with other migraine equivalent symptoms, a characteristic pattern of occurrence of the symptoms, and a positive response to antimigrainous therapy are features that strengthen the diagnosis of a migraine equivalent phenomenon. PMID- 3339926 TI - Hyperlipidemia in association with childhood sensorineural hearing loss. AB - In adults there has been an association noted between hyperlipidemia and sensorineural hearing loss. Etiologic considerations include hyperviscosity of the serum, vascular occlusion and an increased susceptibility to noise. Until now this correlation, to our knowledge, has not been made in the pediatric population. Several children with bilateral fluctuating sensorineural hearing losses have been identified with hyperlipidemia. The fluctuations in hearing varied with lipid levels. With dietary controls, the cholesterol levels returned to what would be near the norm for the pediatric population and hearing returned to near baseline. Unexplained fluctuating sensorineural hearing losses in children warrant the consideration of hyperlipidemia. Discovering a potentially reversible etiology for hearing loss is significant but more importantly, may lead to the early detection of hyperlipidemia in the young patient. PMID- 3339927 TI - Juvenile nasopharyngeal angiofibroma: an update of the UCLA experience, 1960 1985. AB - The UCLA experience with juvenile angiofibroma (JNA) over a 25-year period is reviewed. There were 83 patients, the majority being adolescent males. Surgery was the primary method of treatment for disease not extending intracranially; 63 of 68 patients (92.5%) became asymptomatic with this modality. In patients treated with a single course of primary radiation, 10 of 14 (78.5%) became asymptomatic. Trends in diagnosis and treatment were evaluated. Contrast computerized tomography reliably assesses tumor extent. Preoperative arteriography is essential for the evaluation and embolization of feeding vessels; this in turn significantly reduces operative blood loss and the need for transfusions. Radiotherapy should be reserved for disease extending intracranially and should be in doses of 3,600 cGy or larger. PMID- 3339928 TI - Airway obstruction due to lymphoma of the larynx and trachea. AB - Involvement of the larynx and trachea by lymphoma is an uncommon problem that can cause life-threatening airway obstruction. High grade obstruction, involvement of the soft tissue of the neck, and tracheal deviation can make intubation and tracheotomy hazardous, if not impossible. Tracheotomy can be ineffective with obstruction of the distal trachea. The clinical presentation and treatment of eight patients with lymphoma involving the larynx or trachea are presented with emphasis on airway management. Dramatic tumor response with relief of airway symptoms was achieved with a regimen of radiotherapy, chemotherapy, corticosteroids, helium-oxygen mixtures, humidity, and intensive care unit monitoring. Direct airway intervention, including tracheotomy, was usually successfully and safely avoided. PMID- 3339930 TI - Juvenile malignant melanoma of the head and neck. AB - Malignant melanoma of the head and neck is a potentially lethal disease and considered rare among juveniles. Treatment patterns have historically been dictated by experience with adults, however a paucity of data is available to determine the natural history and treatment guidelines for juveniles and children with malignant melanoma. Therefore a retrospective computer-aided analysis of patients less than 20 years of age having malignant melanoma were obtained from the records of 4,843 patients with malignant melanoma recorded from 1972 through 1986. Eighty-seven patients were identified from this group with 17 patients having primary malignant melanomas confined to the head and neck. Parameters evaluated were age at diagnosis, sex, type of melanoma, Clark Level, Breslow depth of invasion, pathologic classification, site of primary, nodal status at diagnosis, surgical treatment, recurrence rate and site of recurrence, and follow up status. Two of 17 patients had stage II disease and were treated with wide local excision and therapeutic radical neck dissection. Fifteen of 17 patients initially presented with stage I disease were treated with wide local excision. Two of these patients underwent elective radical neck dissection both of which proved to have positive occult nodal disease. Both are alive without evidence of disease 2 1/2 to 7 years later. Of the 13 patients who were initially treated with only wide local excision, nine patients developed local (3), regional (3), or systemic (3) disease within 3 months to 9 years from the date of diagnosis. Seven of the nine died of their disease 5 months to 20 years later. When juvenile patients with melanomas of the head and neck are compared to a comparable age group of patients with melanomas at other primary body sites, the head and neck group had a significantly higher frequency of death. Compared to the adult head and neck population, juvenile patients had identical actuarial survival time, but shorter disease-free intervals, even though the adult population had a higher percent of poor prognostic indices (presence of ulceration and thickness of lesions). Failure to control local and regional disease coupled with the overall poor survival rate, indicates that malignant melanoma occurs in the young as a biologically active tumor and suggests an aggressive approach for better control of local and regional disease and, hopefully, survival. PMID- 3339929 TI - Carotid artery resection and bypass for neck carcinoma. AB - Twenty-six patients were treated by carotid artery resection and vascular replacement for recurrent cancer of the neck. The incidence of postoperative neurologic sequelae was 7%. The absolute 12-month disease-free survival for metastatic squamous cell carcinoma was 25%. It is concluded that in selected patients, this aggressive surgical therapy is indicated. PMID- 3339931 TI - Localized injections of botulinum toxin for the treatment of focal laryngeal dystonia (spastic dysphonia). AB - Spastic dysphonia is a condition producing a strain-strangle phonation. We have previously classified most of these patients as having focal laryngeal dystonia, a disorder of central motor processing. The initial success of recurrent nerve section in many of these patients has been followed by recurrence of symptoms in months to years. Bilateral involvement of the vocal cords with hyperfunction of the nonparalyzed vocal cord could explain these failures. Injection of botulinum toxin (BOTOX) has been effective treatment for many focal dystonias. We have treated more than 100 patients with dystonia including five with laryngeal dystonia. All of the patients laryngeal had dramatic improvement after 48 to 72 hours; benefit lasted 3 to 9 months for each injection period. BOTOX injection can be performed on awake, ambulatory patients. Bilateral treatment and titration of dose can achieve the desired degree of weakness. PMID- 3339932 TI - Dynamic compression plating in treatment of the fractured, edentulous mandible. AB - The repair of a mandibular fracture in the edentulous patient can be a difficult surgical problem. A recent report of a large series of such cases by the University of Michigan disclosed a 20% rate of nonunion. Dynamic compression plating is particularly suited to the repair of fractures of the edentulous mandible as intermaxillary fixation is unnecessary, normal speech and diet are resumed immediately, and bone grafts can be used when necessary. This series of 36 plates used in the management of mandibular fractures in 24 edentulous patients is the largest series of its type reported thus far. No nonunion or other major complication occurred in this series. Because nonunion, delayed union, and the problems associated with intermaxillary fixation were avoided in this series, it is suggested that compression plating is a highly effective method for repair of fractured edentulous mandibles. PMID- 3339933 TI - Quantitative analysis of nasal tip projection. AB - Previously described methods for quantifying nasal tip projection were evaluated. Fifty-one nasal profiles were analyzed and scored by expert rhinoplastic surgeons. The noses and faces were then evaluated quantitatively using several methods. The methods were found to vary widely in their correlation with the experts' subjective analyses. Several helpful relationships and guides were obtained: 1. Aesthetic tip projection does not correlate well with upper lip length. 2. A new method described in this paper showed the best correlation with the experts' opinions (regression, r value = 0.8132). This method related tip projection to total nasal length (including upper lip length). 3. The second new method tested in this report yielded helpful data by comparing tip projection with overall facial length. 4. After slight modification the method previously described by Goode proved useful as nasal length and desired tip projection formed a 3:4:5 right triangle. PMID- 3339934 TI - Intraoperative monitoring of the facial nerve. AB - Anatomic preservation of the facial nerve, with maximal facial function, is one of the goals of acoustic neuroma surgery. Application of electrophysiologic monitoring techniques is useful in achieving this goal. Preoperative electromyography and nerve conduction studies provide important prognostic information for preservation of the nerve and postoperative function. Intraoperative electromyography alerts the surgeon to facial nerve proximity and potential injury. Direct nerve stimulation is utilized to confirm the location and integrity of the nerve. Matched-pair analysis of two groups of patients demonstrated an increased ability to preserve the facial nerve with less postoperative facial deformity. PMID- 3339935 TI - The head and neck sequelae of cervical intravenous drug abuse. AB - When peripheral veins sclerose, addicts desperately seek new and more dangerous injection sites. At Howard University Hospital, Washington, DC, a disturbing increase in intravenous head and neck complications has been observed. From 1982 to 1985, 30 patients demonstrating complications resulting from intravenous cervical injections were treated. Computed tomography is emphasized as the most helpful diagnostic modality. Its timely use enables physicians to formulate early diagnosis and precise surgical intervention. A suggested diagnostic and treatment protocol is presented as a guideline in the management of this potentially deadly phenomenon. PMID- 3339936 TI - Statistical analysis of changes of pediatric nasal patency with growth. AB - The purpose of this study was to further investigate the changes of pediatric nasal patency with growth. The nasal patency of Japanese children aged 6 to 14 years was measured by active anterior mask rhinomanometry in terms of effective cross-sectional area (ECSA). The total nasal ECSA of the boys studied was larger than that of the girls of the same age groups. Total nasal ECSA was significantly correlated to age and height, as not transformed, and to weight as logarithmically transformed. Moreover, our study suggests that pediatric nasal resistance is inversely proportional to the second power of age, of height, and of body weight; however, it was concluded that the parameter of height was in itself sufficient to permit an approximate calculation of the total nasal ECSA in normal subjects. PMID- 3339938 TI - Artificial reflex arc: a potential solution for chronic aspiration. II. A canine study based on a laryngeal prosthesis. AB - Long-term and repeated aspiration can result in pneumonia and eventually death. To avoid current techniques which divert or close off the incompetent larynx, the authors have recently described an artificial reflex arc (ARA), in hopes of providing a dynamic solution to this problem. With this concept, a segment of skin surface with intact sensory innervation is implanted into the pharynx in the path of the food bolus. Resulting neural impulses would be detected by a perineural electrode and then channeled to both recurrent laryngeal nerves via an electronic pacemaker to cause vocal fold adduction at the critical time during swallowing. A pilot study using a tubed cervical cutaneous surface has yielded promising results in the canine. In this current study, an alternate means for information pickup based upon use of a miniature strain gage is presented. Mechanical stimulation of the hypopharynx using this "sensory" detector resulted in synchronous laryngeal adduction of the vocal folds, as documented graphically and on videotape. PMID- 3339937 TI - Cephalometric analysis for diagnosis and treatment of obstructive sleep apnea. AB - A detailed cephalometric analysis was conducted on lateral x-rays from 30 adult patients with obstructive sleep apnea (OSA) and 12 age- and sex-matched controls. Statistical findings show that OSA patients are different from controls in at least five ways: 1. Their tongue and soft palate are significantly enlarged. 2. The hyoid bone is displaced inferiorly. 3. The mandible is normal in size and position (no micrognathia or malocclusion), but the face is elongated by an inferior displacement of the mandibular body. 4. The maxilla is retropositioned and the hard palate elongated. 5. The nasopharynx is normal, but the oropharyngeal and hypopharyngeal airway is reduced in area by an average of 25%, a factor that could produce or enhance OSA symptoms. These data suggest that cephalometric evaluation could be useful when used with head and neck examination, polysomnographic and endoscopic studies to evaluate OSA patients, and to assist with the planning/surgical treatment for improvement of upper airway patency. PMID- 3339939 TI - Adjustable dissection and surgical table as an aid to teaching. AB - An adjustable dissection and surgical table for teaching residents, fellows, staff, and other medical and allied health personnel about anatomy and simulated techniques of surgery in the laboratory setting is described. The table can be attached to a standard House-Urban temporal bone dissection bench. The temporal bone laboratory can thus serve a dual purpose in teaching ear and soft tissue anatomy and surgical techniques of the head and neck. In this setting such a dual purpose laboratory can often include basic and clinical research activities as a third function. PMID- 3339940 TI - A technique for insertion and removal of an intraoral drain following treatment of a retropharyngeal abscess. PMID- 3339941 TI - A simple device for tympanocentesis in infants and children. PMID- 3339942 TI - The effect of aging on cutaneous lipid peroxide levels and superoxide dismutase activity in guinea pigs and patients with burns. AB - Cutaneous lipid peroxide levels and superoxide dismutase (SOD) activity in non aged and aged guinea pigs were measured between 15 min and 7 days after experimental infliction of burns. Skin burns on non-aged and aged patients were also subjected to these assays. In non-aged guinea pig skin burns, lipid peroxide levels increased from 24 hr to the fourth day after the burn infliction, while SOD activity did not increase but showed a slight decrease 12 hr and 24 hr post burn. On the other hand, while the aged group showed a more increase in skin lipid peroxide levels compared to that seen in non-aged mice, skin SOD activity began to decrease from 30 min post-burn, the maximum decrease being reached on the second day. The activity did not return to normal by the 7th day. In non-aged patients skin burns showed increases in both lipid peroxide levels and SOD activity, while in aged patients, though they showed a marked increase in lipid peroxide levels, SOD activity remained unchanged. The present study indicated that, although in our recent study, skin SOD activity of healthy elderly people was found to be comparable to that in non-aged individuals, the capacity for induction of SOD activity under oxygen stress differed with age in both guinea pig and human burn sufferers. Furthermore, this induction capacity seemed to vary from species to species. PMID- 3339943 TI - Water-maze learning and effects of cholinergic drugs in mouse strains with high and low hippocampal pyramidal cell counts. AB - Morphological differences have been found in inbred strains of mice in the number and volume of pyramidal cells in Ammon's horn of the hippocampus. Among the mouse strains surveyed, NZB/BINJ (NZB) and C57BL/10J (B10) are most divergent in both total volume and total number of neurons. These genetically derived differences were exploited to determine hippocampal involvement in the acquisition of a spatial water maze. Genetic differences in hippocampal cell number were related to the acquisition of this spatial task. Mice with small numbers of hippocampal pyramidal cells, the B10 strain, acquired a water-maze task more slowly than either NZB mice or (NZBxNZW) F1 (NZBWF) animals. In addition, strain differences in responsivity to cholinergic manipulations were found. B10 mice were more sensitive than NZB or NZBWF mice to both the disruptive effects of scopolamine and the facilitory effects of physostigmine on swim maze learning. Although other inherited differences undoubtedly exist between these strains as is apparent in other mouse lines, these data suggest a prominent role for the hippocampus in the learning of spatially oriented behavior. Furthermore, this behavior appears to be responsive to cholinergic manipulations. PMID- 3339944 TI - The effects of in vitro lipid peroxidation on the activity of rat liver microsomal glutathione S-transferase from rats supplemented or deficient in antioxidants. AB - Glutathione S-transferases are a group of multifunctional isozymes that play a central role in the detoxification of hydrophobic xenobiotics with electrophilic centers (1). In this study we investigated the effects of in vitro lipid peroxidation on the activity of liver microsomal glutathione S-transferases from rats either supplemented or deficient in both vitamin E and selenium. Increased formation of malondialdehyde (MDA), a by-product of lipid peroxidation, was associated with a decreased activity of rat liver microsomal glutathione S transferase. The inhibition of glutathione S-transferase occurred rapidly in microsomes from rats fed a diet deficient in both vitamin E and selenium (the B diet) but was delayed for 15 minutes in microsomes from rats fed the same diet but supplemented with these micro-nutrients (B+E+Se diet). Lipid peroxidation inhibits microsomal glutathione S-transferase and this inhibition is modulated by dietary antioxidants. PMID- 3339945 TI - Theophylline neurotoxicity in pregnant rats. AB - The purpose of this investigation was to determine whether the neurotoxicity of theophylline is altered in advanced pregnancy. Sprague-Dawley rats that were 20 days pregnant and nonpregnant rats of the same age and strain received infusions of aminophylline until onset of maximal seizures which occurred after 28 and 30 minutes respectively. Theophylline concentrations at this endpoint in serum (total) and CSF were similar but serum (free) and brain concentrations were slightly different in pregnant rats. Theophylline serum protein binding determined by equilibrium dialysis was lower in pregnant rats. Fetal serum concentrations at onset of seizures in the mother were similar to maternal brain and CSF concentrations and correlated significantly with the former. It is concluded that advanced pregnancy has a negligible effect on the neurotoxic response to theophylline in rats. PMID- 3339947 TI - Simultaneous determination of chloroquine and metronidazole in human biological fluid by high pressure liquid chromatography. AB - Chloroquine (CQ) and metronidazole (MZ) were measured in human urine and plasma by HPLC with UV detection. This method was used to analyse plasma levels in 4 African volunteers after an oral dose of 1000 mg CQ and 750 mg MZ, in a European on weekly prophylaxis of 500 mg CQ, and on 50 hospital urine samples. In the Africans peak plasma levels were over 1 microgram/ml and peak time was 1 1/2-2 hr. In the European plasma levels ranged from 0.58 to 0.36 microgram/ml. Over 80% of the urine samples contained CQ, MZ or both. The assay system was found flexible and economical for the therapeutic monitoring of these two important tropical drugs. PMID- 3339946 TI - Lipolytic activities of freshly isolated rat liver parenchymal cells. AB - By using a specific collagenase preparation preserving lipolytic enzymes, we could isolate intact rat liver cells with monoester lipase (MEL) and, for the first time, substantial amounts of endogenous neutral triester lipase (TEL) activities assayable as cell-bound enzymes. TEL and MEL activities were found exclusively in parenchymal cells. Virtually all TEL was located on plasma membrane from which it was rapidly released at 37 degrees C in the absence of any additive. MEL was distributed almost equally inside the cell and in the membrane, to which it was firmly attached. Infusion of heparin to the whole animal before liver exposure decreased by 80% the TEL content of parenchymal cells (a property typical of hepatic lipase) whilst MEL was unchanged. These results question the concept that heparin-releasable hepatic lipase acts at the surface of endothelial liver cells and further suggest that TEL and MEL refer to distinct catalytic entities. PMID- 3339949 TI - Different components of 3H-imipramine binding in rat brain membranes: relation to serotonin uptake sites. AB - In the present paper we confirm and extend previous studies showing heterogeneous 3H-imipramine (3H-IMI) binding sites. Inhibition curves of various drugs (serotonin, imipramine, desmethyl-imipramine, d-fenfluramine, d-norfenfluramine and indalpine, a potent serotonin uptake inhibitor) obtained using 2 nM 3H-IMI and in presence of 120 mM NaCl, confirmed the presence of at least three 3H-IMI binding sites: two of these (high and low affinities) were serotonin-insensitive while the third one was selectively inhibited by serotonin and indalpine with nanomolar affinities. Moreover, this last component was found to be selectively modulated by chronic imipramine treatment thus suggesting a closer relation to serotonin uptake mechanism. These data indicate that the use of a more selective inhibitors of the serotonin-sensitive component (like indalpine or serotonin itself) to define non specific 3H-IMI, may be of help in understanding its relation with serotonin uptake system. PMID- 3339948 TI - Interaction between veralipride and the endogenous opioid system in the regulation of body temperature in postmenopausal women. AB - The influence of endogenous opioid peptides on body thermoregulation has been studied in untreated postmenopausal women and in the same subjects after chronic administration of the antidopaminergic drug veralipride (200 mg/day for 20 days). Subjects randomly received an infusion of the opioid antagonist naloxone (1.6 mg/h for 4 h) or saline on two consecutive days, both before and after veralipride treatment. In untreated subjects body core temperature, as evaluated by rectal temperature, did not vary during saline infusion, whereas a significant decrease was observed during naloxone infusion. Chronic administration of veralipride significantly increased the hypothermic response to naloxone. Therefore, veralipride seems to increase the activity of endogenous opioid peptides on mechanisms which regulate body temperature in postmenopausal women. PMID- 3339950 TI - The intrinsic activity of (-)-3-PPP (preclamol) on pituitary DA receptors in female rats is enhanced following chronic DA depletion. AB - The present investigation was aimed at comparing the influence of the partial dopamine (DA) receptor agonist (-)-3-PPP (preclamol) on prolactin release in acutely hyperprolactinemic but otherwise intact female rats and female rats subjected to chronic DA depletion. One group of animals received daily vehicle injections (controls) and another group daily reserpine (1 mg/kg) injections for a period of seven days. On the eighth day all animals were administered 10 mg/kg of reserpine in order to eliminate endogenous DA and elevate serum prolactin levels. In the control group (-)-3-PPP lowered serum prolactin levels only moderately. In contrast, in the chronically reserpinized female rats, a pronounced reduction of prolactin secretion was observed. It is suggested that this increase in intrinsic activity of (-)-3-PPP following chronic DA depletion reflects an enhanced responsiveness of hypophyseal DA receptors, possibly due to conformational changes in the receptor molecules. Our observations lend further support to the hypothesis that an inverse relationship exists between the intrinsic activity of a mixed agonist/antagonist and the degree of previous receptor occupancy. PMID- 3339952 TI - Diltiazem does not increase the in vivo sensitivity of murine hemopoietic progenitor cells to doxorubicin. AB - The effect of doxorubicin and the calcium antagonist, diltiazem, on murine hemopoietic progenitor cells was studied in vivo. Dose-survival curves of murine bone marrow colony forming units (CFU)--spleen and granulocyte macrophage--were determined by in vivo and in vitro methods in DBA/2NCr/BR mice treated with doxorubicin alone or by simultaneous administration of doxorubicin (DX) and diltiazem (DTZ). Time response of bone marrow hematopoietic progenitor cells (HPC) was followed in mice similarly treated. Combination of DTZ with DX did not change the toxic effect of the latter on hemopoietic cells, either in the dose survival model or in the time-related experiment. PMID- 3339951 TI - Study of digoxin as inhibitor of the in vivo effects of acetyl glyceryl ether phosphorylcholine (AGEPC) in mice. AB - Acetyl glyceryl ether phosphorylcholine (AGEPC) and the cardiac glycoside digoxin were administered intravenously through the tail vein into ether-anesthetized SWR mice (two months old). The administered doses were 0.18 nmol AGEPC/g b.w. (a lethal one) and 75 or 125 ng digoxin/b.w. Digoxin ameliorates the effects of the lethal dose of AGEPC showing maximum activity when given 5 or 10 min after AGEPC administration to female and male animals respectively. Digoxin shows also a protective action towards the effects of AGEPC and maximum activity appears when it is given 10 min before AGEPC administration. In agreement with the picture of increased survival in digoxin pretreated animals, are our findings on life prolongation of mice which finally die from AGEPC, the amelioration of the expected fall in blood platelet counts after AGEPC administration as well as the improved performance of the animals in a series of physical tests. PMID- 3339953 TI - Extraneuronal accumulation of isoproterenol in atria and ventricle of perfused rat heart. AB - Extraneuronal accumulation of isoproterenol in atria and ventricle of perfused rat heart was investigated. Rat hearts were perfused with various concentrations of 3H-isoproterenol for 30 min in the absence and the presence of catechol-O methyltransferase (COMT) inhibitor (tropolone). When COMT was intact, the accumulation of 3H-isoproterenol in both atria and ventricle after perfusion with low concentration of 3H-isoproterenol (0.01 to 1 mumol/l) was less than that of perfusing concentration; the tissue/medium ratio (T/M) of isoproterenol for artia was lower than that for ventricle. The T/M of isoproterenol after perfusion with 10 and 20 mumol/l of 3H-isoproterenol were 0.94 and 1.76 for atria and 3.25 and 2.95 for ventricle, respectively. When COMT was inhibited by tropolone, the T/M increased 6.3-9.0 folds for atria and 5.1-6.7 folds for ventricle after perfusion with 3H-isoproterenol (0.01 to 1 mumol/l). From these results, it was concluded that both atria and ventricle of the rat heart have an extraneuronal O methylating system as reported in rat whole heart, and was suggested that there might be different capacities of extraneuronal uptake and COMT between them. PMID- 3339954 TI - Role of baroreflex in the pressor response of rats with hypertension developed by renal artery stenosis. AB - We examined the interrelationships between the pressor response to the administration of norepinephrine and arginine vasopressin and baroreflex function in rats with hypertension of two days' duration induced by heminephrectomy and a clip placed on the right renal artery (2-day clipped rats). Mean arterial pressure was higher in the 2-day clipped rats than in heminephrectomized rats without clips (sham-operated rats). The pressor response in the 2-day clipped rats to both agents increased as compared to the sham-operated rats. This hyperresponsiveness was attenuated by administering an angiotensin II antagonist, [1-Sar, 8-Ile] angiotensin II. Baroreflex sensitivity was studied by measuring changes in arterial pressure and pulse interval in response to the injection of phenylephrine. Baroreflex sensitivity was not decreased but markedly increased in the 2-day clipped rats and unaffected by infusing the angiotensin II antagonist. These results provide evidence that 1) in the 2-day clipped rats there are exaggerated pressor responses to vasoconstrictors; 2) the hyperresponsiveness is not causally related to the change of baroreflex sensitivity; and 3) angiotensin II plays a significant role in the increased pressor responses; however, the baroreflex mechanism is not involved in attenuation of the hyperresponsiveness by the angiotensin II antagonist. PMID- 3339955 TI - Comparative studies of the ingestive behaviors produced by microinjections of muscimol into the midbrain raphe nuclei of the ventral tegmental area of the rat. AB - Microinjection of the GABA-A agonist muscimol into the median (MR) or dorsal (DR) raphe nuclei or the ventral tegmental area (VTA) of non-deprived rats induced intense feeding and drinking in a dose-dependent and site-specific manner. Lower doses of muscimol were required to increase food intake, spillage and water intake with injections into the MR than with injections into the other two sites. These data demonstrate that the MR is a more sensitive site for the elicitation of ingestive behavior than either the DR or the VTA. PMID- 3339956 TI - Pharmacology and molecular identification of secretin receptors in rat gastric glands. AB - The structure of the secretin receptor in purified plasma membranes isolated from the antral and fundic parts of the rat gastric mucosa was probed, using the cross linking reagent dithiobis succinimidyl propionate (DSP) and HPLC-purified [125I] secretin. [125I] secretin binding sites were preferentially located in rat antrum and displayed the pharmacological properties expected for specific secretin receptors: secretin greater than helodermin greater than rhGRF greater than rPHI. SDS gel electrophoresis of the solubilized receptor allowed identification of two radiolabeled peptides of 62 and 33 KDa connected by disulfide bonds. According to the sensitivity of the 62 KDa component to low doses of secretin and to GTP, it constitutes the membrane domain involved in the physiological regulation of adenylate cyclase by secretin in rat gastric glands. PMID- 3339958 TI - Tort reform legislation. PMID- 3339957 TI - Fewer metabolites of dietary choline reach the blood of rats after treatment with lithium. AB - Choline is an important precursor for the biosynthesis of acetylcholine, phosphatidylcholine and sphingomyelin. It is also a major source of labile methyl groups. Lithium is an important component of the treatment of bipolar affective illness, and it inhibits choline transport across membranes. We studied the effect of lithium treatment upon the appearance in blood, liver and intestine of metabolites formed from dietary choline. Rats were treated for 9 days with 2 mEq/kg lithium carbonate or water. Animals were fasted overnight, and on the 10th day were fed with a solution containing radiolabeled choline chloride. The lithium-treated groups also received 2.0 mEq/kg lithium as part of this solution. After an oral dose of 1 ml of a 1 mM choline solution, the lithium-treated animals had significantly lower levels of choline-derived radiolabel in blood than did controls at 30, 60, 120, and 180 minutes (47% (+/- 5%; SEM), 51% (+/- 7%), 59% (+/- 4%) and 74% (+/- 9%), respectively). We observed similar decreases of the accumulation in blood, at 180 minutes after the dose, of choline-derived radiolabel when choline was administered at lower or higher concentrations. After an oral treatment containing 0.1, 1 or 10 mM choline, lithium treated animals accumulated 69% (+/- 6%; SEM), 66% (+/- 11%) and 72% (+/- 7%) as much radiolabel in serum as did controls. Most of the radiolabel found in blood at 180 minutes was in metabolites of choline which are formed within liver (betaine and phosphatidylcholine). The diminished accumulation of radiolabel in serum after lithium treatment was not due to increased accumulation of label by erythrocytes, liver or gut wall. We suggest that lithium influences the release by liver of betaine and phosphatidylcholine. PMID- 3339959 TI - Munchausen syndrome by proxy: a psychodynamic analysis. PMID- 3339960 TI - Dentistry and AIDS: ethical and legal obligations in provision of care. PMID- 3339961 TI - Research ethics committees and the regulation of medical experimentation with human beings in The Netherlands. PMID- 3339962 TI - Alcohol consumption and crimes against sexual freedom. PMID- 3339964 TI - In re B. (a minor) (wardship: sterilisation). PMID- 3339965 TI - Brief psychiatric treatment. PMID- 3339963 TI - Comparison of problem drinkers known to agencies with problem drinkers in the general population. PMID- 3339967 TI - Cholesterol treatment recommendations for adults. Highlights of 1987 report, National Cholesterol Education Program Adult Treatment Panel. PMID- 3339968 TI - Lobbying the legislature: a practitioner's guide. PMID- 3339969 TI - Malpractice in Maryland--the legislative outlook. PMID- 3339966 TI - The Thyroid gland. PMID- 3339970 TI - The importance of physician-patient communication in reducing medical liability. PMID- 3339971 TI - Optimal selection of a battery of tests: a multiobjective optimization methodology. AB - The general problem of selecting a battery of tests for diagnostic purposes is discussed and multiobjective optimization methodology is applied to solve it, with battery selection being based on performance indices such as sensitivity, specificity, and the cost of testing. For a battery of tests, the extended majority rule is developed and used to interpret the compound test results. The major advantage of the model developed in this paper is that it can generate a set of noninferior batteries without requiring the calculation of all possible combinations of tests. An example in which the method is applied to a real problem--the selection of short-term tests to detect the carcinogenicity of chemicals--is discussed. PMID- 3339972 TI - Increasing the power of clinical trials through judgment analysis. AB - A method for increasing the statistical power of clinical trials to detect clinically important differences is described. Inconsistency in physicians' overall judgments of treatment effectiveness adds "noise" to a trial that may mask either the superiority or the inferiority of particular treatments. The method described here uses "judgment analysis" to reduce errors in an individual's overall judgments of treatment effectiveness. The method can also be used to reduce error variance due to differences in judgment between physicians and may thus be particularly useful in multicenter trials. The method is illustrated with results from a recent trial. PMID- 3339973 TI - On extending judgment analysis to clinical trials. PMID- 3339974 TI - [Selective accumulation of 131I-labeled IKO-1 monoclonal antibodies in the tissues of mouse L 1210 lymphoid leukemia]. AB - Monoclonal antibodies (MCA) ICO-1 of IgG3 isotype against 1a-like human antigens were labelled with 131I using chloramine T; a radionuclide-bound fraction was isolated by radiochromatography. Basing on the results of assessment of complement-dependent cytotoxicity against lymphocytes from the lymph nodes of BDF1 mice a conclusion was made that MCA immunological reactivity changed slightly after radionuclide tracer administration. In vitro experiments with a panel of normal and malignant cells showed 131I-MCA binding with cells of mouse lymphoid leukemia L1210 and hemocytoblastosis La as well as with spleen and lymph node normal lymphocytes. During in vivo experiments 131I anti-la MCA at a dose of 30 micrograms (specific activity of 32.10(10) Bq/mmol) was administered intravenously to BDF1 mice with transplantable lymphoid leukemia L1210. Radiometry of the organs 24 h after administration of antibodies showed their accumulation in a solid tumor localized on intestinum tenue mesenteriale. The ratio of concentrations of labelled antibodies (in % of the administered amount per 1 g) of tumor/blood was 2.4, that of tumor/liver--4.5. For normal nonimmune 125I-IgG this rate was 0.4 and 0.7, respectively. A high level of MCA in the blood is a factor decreasing MCA diagnostic potentialities. The use of F(a, b) fragments may considerably decrease the role of this factor. The data obtained suggest a possibility of the use of MCA ICO-1 for in vivo radioimmunoassays of some hematological tumors. PMID- 3339975 TI - [Radiotherapy of malignant lymphoma of the orbit]. AB - Gamma-beam therapy of malignant orbital lymphomas of 1 year to 7 years 5 months duration ensured the cure of a primary orbital focus in all 8 patients. The total focal dose of 30 Gy (10 irradiation sessions) was sufficient for control. Generalization was noted in 3 (42.8%) patients, one patient died from intercurrent disease in 7 months. Taking into account some features of metastasizing and avoiding the first barrier of the lymph nodes their elective irradiation was not recommended. PMID- 3339976 TI - [Combined radiotherapy of esophageal cancer]. AB - The paper is concerned with the results of combined radiotherapy of 60 esophageal cancer patients. Indications for combined radiotherapy were the minimum lumen of the esophagus (8-10 mm), limited local spreading of a tumor, and the absence of distant metastases. Among the patients there were 46 men, 14 women, their mean age was 56-8.3 yrs. The mean duration of life of the dead patients was 16.2-7.2 months. No cardiac or pulmonary complications were observed. The 3-year survival rate was 26.4-6.9% and the 5-year survival rate was 17.8-6.1%. PMID- 3339978 TI - [Long-term results of radiotherapy of pancreatic cancer]. AB - Long-term results of radiotherapy of 131 pancreatic cancer patients were discussed. The mean survival time after the therapy was 15.6 mos., in patients with histologically verified diagnosis of cancer--15 mos. During 1 year 64.4% of the patients survived, 2 years--44.7%, 3 years--35.2%, 4 years--9.6%, 5 years- 3.2%. The results obtained were 2.5-fold better than those after biliodigestive anastomoses and 3-fold better than those after chemotherapy. Irradiation within a short period (0.5-1 month) after palliative or exploratory operation (the mean survival time was 20.9 mos.) seemed one of the most realistic methods for improving therapeutic results in pancreatic cancer. The mean survival after placing cholecystojejunoanastomosis and radiotherapy was 17.7 mos. (from the onset of irradiation), after exploratory laparotomy and irradiation--18.9 mos., after palliative tumor resection and irradiation--23.9 mos. The efficacy of radiotherapy was lowered with increasing an interval between explorative or palliative operation and irradiation. A split course of gamma-beam therapy was recommended depending on a patient's general status (10-20 after Karnovsky). PMID- 3339977 TI - [Efficacy of the conservative treatment of patients with inoperable esophageal cancer]. AB - The results of gamma-beam therapy of esophageal cancer leave much to be desired. However betatron therapy improves them. To compare the results of esophageal cancer therapy 4 therapeutic modalities were employed: the 1st group- chemoradiotherapy (methotrexate at a weekly dose of 45 mg), the 2nd group- chemoradiotherapy (methotrexate at a dose of 10 mg alternating with prospidin at a dose of 200 mg), the 3rd group--radiotherapy (inhibitory radiation), the 4th group--radiotherapy (gamma-beam therapy). Higher efficacy of chemoradiotherapy as compared to radiotherapy only was established. PMID- 3339979 TI - [Functional status of the cardiovascular system in Hodgkin's disease and the effect of radiotherapy]. AB - The main indices of cardiohemodynamics, phase structure of the cardiac cycle and ECG were studied in 34 patients with Hodgkin's disease aged 16 to 43: before the initiation of therapy, after a course of radiotherapy and in long term after therapy. The patients were characterized by tachycardia increasing with a degree of a process, ECG signs of myocardiodystrophy, a tendency to the formation of the phase syndrome of hypodynamia, slight pulmonary hypertension, a decrease in AP and peripheral vascular resistance. After a course of radiotherapy according to a radical program functional indices of the cardiovascular system in most of the patients returned to normal. However signs of radiation pericarditis with a favorable clinical course developed in some patients. Long after therapy positive changes in the cardiovascular system were noted among patients with IIA stage, negative shifts were noted in patients with III-IV stage. PMID- 3339980 TI - [Terminology problems in medical thermography]. AB - The paper is devoted to some problems of medico-technical terminology of clinical thermography. A short historical review of stages of the discovery of infrared rays and their medical application was given. An analysis of a number of terms is based on the rules of medical terminology and state standards. An obligatory use in literature of correct terms, mainly of the Greek and Latin origin, is proposed. Commonly used terms on the basis of modern anatomical terminology are recommended for thermogram description. PMID- 3339981 TI - [Increase in the radiosensitizing properties of metronidazole as affected by irradiation and moderate whole-body drug-induced hyperthermia]. PMID- 3339982 TI - [Radiation and combined therapy of esthesioneuroblastomas]. PMID- 3339983 TI - [Population analog of the Blair-Davidson-Korogdin model]. AB - The author compares different models of fractionated irradiation (Blair-Davidson Korogodin, F. Ellis and L. Cohen). It has been established that if F. Ellis' and L. Cohen's models well reflect the correlation of a skin tolerance dose and time intervals between irradiation sessions, the beta-parameter in the Blair-Davidson Korogodin model is a function of time intervals and the of parameter remains constant. The population analog of the Blair-Davidson-Korogodin model was proposed for the first time. The use of the analog can facilitate its analysis and comparison with other models of fractionated irradiation. PMID- 3339984 TI - [Scintigraphy of the lacrimal ducts]. AB - Dynamic scintigraphy of the lacrimal ducts with various degrees of their permeability was performed in 8 patients, in 2 of them it was repeated. 99m Tc and 99m In-colloidal preparations were used. The data obtained made it possible to recommend the method for assessment of permeability and function of the lacrimal ducts. Scintigraphy of the lacrimal ducts appeared to be the least traumatic and more functional method as compared to x-rays. PMID- 3339985 TI - Bedside terminals: MedTake. PMID- 3339986 TI - Bedside terminals: CliniCom. PMID- 3339987 TI - Upper extremity fitness training. PMID- 3339988 TI - Assessing your billing policies and practices. PMID- 3339989 TI - Laboratory information systems. PMID- 3339991 TI - Bedside terminals: an overview. PMID- 3339990 TI - Predicting height and auxologic follow-up using microcomputers. PMID- 3339992 TI - Ivy practice information management systems. PMID- 3339993 TI - Who's in the waiting room? PMID- 3339994 TI - Role of spatial location in learning face-name associations. PMID- 3339995 TI - The role of memory in attenuations of the suffix effect. PMID- 3339997 TI - Conceptual transfer in simple insight problems. PMID- 3339996 TI - Serial search and comparison of features of imagined and perceived objects. PMID- 3339998 TI - Cognitive arithmetic: evidence for obligatory activation of arithmetic facts. PMID- 3340000 TI - Similar as well as dissimilar contextual stimuli increased rated similarity. PMID- 3339999 TI - Evidence for processing of constituent single- and multiletter codes: support for multilevel coding in word perception. PMID- 3340001 TI - When category learning is holistic: a reply to Ward and Scott. PMID- 3340002 TI - Qualitative and quantitative considerations in encoding difficulty effects. PMID- 3340004 TI - The effect of small increases in dietary iodine on thyroid function in euthyroid subjects. AB - Dietary iodine intake in the United States is greater than that considered necessary for the maintenance of normal thyroid function. The administration of pharmacologic quantities of iodine (10 to 1,000 mg daily) to euthyroid subjects results in small decreases in the serum T4 and T3 concentrations and a compensatory increase in the basal and TRH-stimulated serum TSH concentrations. Studies were carried out to determine whether a far smaller increase in iodine intake would also affect thyroid function. Normal volunteers received 1,500, 500, or 250 micrograms supplemental iodine daily for 14 days. Following the administration of 1500 micrograms iodine daily, there were small but significant decreases in the serum T4 and T3 concentrations and a small compensatory increase in the serum TSH concentration and the serum TSH response to TRH. In contrast, no changes in pituitary-thyroid function occurred during the administration of 500 or 250 micrograms iodine daily. These findings indicate that a small increase in dietary iodine can induce subtle changes (all values remaining within the normal range) in pituitary-thyroid function, probably by inhibiting thyroid hormone release. The smaller iodine supplements of 500 and 250 micrograms daily, quantities that may easily be achieved under normal conditions, did not, however, affect thyroid function. PMID- 3340005 TI - Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency. AB - Homocysteine is an amino acid considered to cause vascular injury, arteriosclerosis, and thromboembolism. Total plasma homocysteine (free and protein-bound) was found to be twice as high in asymptomatic vitamin B12 deficient subjects (23.8 +/- 3.8 mumol/L, means +/- SEM, n = 20) as in controls (11.5 +/- 0.9 mumol/L, P less than .0001, n = 21), and higher than in heterozygotes for homocystinuria due to cystathionine beta-synthase deficiency (13.8 +/- 1.6 mumol/L, P less than .01, n = 14), who were recently shown to be much more common among patients with premature vascular disease than expected. Eight (40%) vitamin B12-deficient and two (14%) heterozygote subjects had significant homocysteinemia (greater than mean +2 SD for controls). After administration of hydroxycobalamin to vitamin B12-deficient subjects, homocysteine levels decreased to normal (-49%, 12.2 +/- 1.5 mumol/L, P less than .0001, n = 20). Thus, if homocysteine does cause vascular injury, theoretically vitamin B12-deficiency might be associated with an increased frequency of vascular disease. PMID- 3340003 TI - Energy expenditure and body composition in Prader-Willi syndrome. AB - Patients with Prader-Willi syndrome are frequently obese. To determine if obesity is partially explained by a low energy expenditure, we compared total daily energy expenditure, basal metabolic rate, and body composition in Prader-Willi patients with obese controls. Total energy expenditure was measured by doubly labeled water, basal metabolic rate was measured by respiratory gas analysis using an open-system canopy design, and body composition was calculated from total body water determinations using 18O labeled water. In six Prader-Willi subjects, basal metabolic rates were normal when compared on the basis of fat free mass, but not body surface area or height, weight, and age. Ten Prader-Willi subjects (8 to 24 years-old) had a total daily energy expenditure (+/- SD) of 1,980 +/- 580 kcal/d, which was 47% less than their obese controls (3,700 +/- 820 kcal/d). When normalized for their smaller fat free mass and body mass, however, the difference was only 14% (P less than .01). The results indicate that the low energy expenditures in Prader-Willi syndrome are mostly due to the small fat free mass in these patients and not due to any difference in energy efficiency at the cellular level. Prader-Willi subjects who had lost weight and were at or near weights appropriate for their heights were still 30% to 40% body fat. Because this excess fat was not evident from skinfold measures, usual anthropometric measures were not reliable indicators of total body fat in these subjects. PMID- 3340006 TI - Glucocorticoid regulation of glycosaminoglycan synthesis in cultured human skin fibroblasts: evidence for a receptor-mediated mechanism involving effects on specific de novo protein synthesis. AB - Human skin fibroblast cultures synthesize and accumulate glycosaminoglycan (GAG). This laboratory has reported recently that the synthetic rate of hyaluronate (HA), the most abundant GAG produced by these cells, is inhibited by glucocorticoids. The purpose of these studies was to characterize further that hormonal response. Effects of potent glucocorticoid agonists dexamethasone (Dex) and RU28362 on GAG synthesis were studied. Both steroids inhibited [3H]GAG synthesis when added 24 hours before labeling with [3H]acetate. RU28362 inhibited HA synthesis by 58% and Dex by 60%. The half-maximal effect for each was achieved at a concentration of 0.5 nmol/L and maximal effects at 10 nmol/L. The recently described glucocorticoid antagonist RU38486 failed to alter [3H]GAG synthesis at concentrations up to 1,000 nmol/L. However, this compound did block the inhibition of the agonists. At concentrations of RU28362 and Dex that maximally inhibited [3H]GAG synthesis (10 nmol/L), RU38486 attenuated the glucocorticoid effect in a dose-dependent manner, with half-maximal inhibition at 5 nmol/L and maximal inhibition at 100 nmol/L. The antagonist blocked as much as approximately 80% of the Dex inhibition and approximately 70% of the RU28362 inhibition. Cycloheximide (25 micrograms/mL) inhibited [3H]HA synthesis by 55% within four hours of its addition to the culture. When cultures were pretreated with cycloheximide without or with Dex (100 nmol/L) for three hours and then treated with actinomycin D (2 micrograms/mL) followed by [3H]acetate labeling, Dex pretreated cultures synthesized 33% less [3H]GAG, implying that Dex had decreased the abundance of a translatable mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3340007 TI - Interrelations between plasma free and protein-bound homocysteine and cysteine in homocystinuria. AB - To study the interrelations between plasma free and protein-bound homocysteine and cysteine, we measured the levels of these four variables in 167 samples from 17 patients with homocystinuria during different treatment regimens, 14 heterozygotes for cystathionine B-synthase deficiency, and 17 normal subjects. There was a strong positive correlation between free and protein-bound homocysteine, and between free and protein-bound cysteine over a wide range of values in varying clinical situations, but homocysteine and cysteine had differing binding characteristics. At low concentrations homocysteine bound more tightly than cysteine to plasma protein, while at high concentrations of the free amino acids more cysteine than homocysteine was bound to plasma protein. In patients with homocystinuria due to cystathionine B-synthase deficiency, levels of protein-bound homocysteine after an overnight fast were eight to 12 times higher than mean levels +/- SD in the normal subjects of 0.15 +/- 0.03 mumol/g of plasma protein, n = 17, and levels of protein-bound cysteine were lower than mean normal levels +/- SD of 2.30 +/- 0.23 mumol/g, n = 17. In the patients before treatment the proportions of both plasma thiols that were protein-bound were approximately half those in the normal subjects. For homocysteine the proportion was 35% in a representative patient and 78% in normal subjects and in heterozygotes, while for cysteine the corresponding proportions were 26% and 59%. In all blood samples the sum of the plasma free and protein-bound homocysteine and cysteine remained relatively constant (mean +/- SD = 270.6 +/- 68.6 mumol/L of plasma, n = 142).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3340009 TI - Impotence and diabetes. AB - The link between impotence and diabetes has been suspected since the 1700s, but it has been only within the last few decades that it has been scientifically investigated and confirmed. Of the 5 million diabetic men in the United States, 30% to 60% suffer from impotence, a complication of their disease that many of them fear more than any other, including blindness. Diabetes is the leading physiologic cause of impotence, and it occurs in both insulin-dependent and non insulin dependent patients. In most cases, there is no relationship between the control, the duration, or the severity of diabetes and the occurrence of impotence. Treatment methods range from adjustments in nutrition to penile implants. PMID- 3340008 TI - Nuclear triiodothyronine receptor of human adipose tissue. AB - L-Triiodothyronine induces malic enzyme in explants from human adipose tissue. Consequently, we looked for the presence of receptors for L-triiodothyronine in nuclei isolated from human adipose tissue. The binding of 125I-triiodothyronine by the nuclei was time- and temperature-dependent. At 37 degrees C binding reached a steady state after 60 minutes. Dithiothreitol enhanced total binding and suppressed nonspecific binding. Scatchard analysis showed the presence of a single class of binding sites. The apparent association constant, Ka, was 0.13 +/ 0.03 X 10(10) M-1, the maximal binding capacity 2.20 +/- 0.81 pmol/mg DNA (mean +/- SD, n = 7) and the number of binding sites 8,000/nucleus. L-Triiodothyronine and D-triiodothyronine had equal affinity to the nuclear receptor; triiodothyroacetic acid had three times higher affinity. L- and D-thyroxine had 8% and 12%, respectively, and tetraiodothyroacetic acid had 19% affinity compared to that of L-triiodothyronine. Reverse triiodothyronine was a weak competitor. Digestion of nuclei with micrococcal nuclease abolished specific binding. These results show that nuclei from human white adipose tissue possess high affinity receptors for L-triiodothyronine, which are associated with nuclear chromatin. It is likely that induction of malic enzyme in human adipose tissue by L triiodothyronine is mediated by the nuclear receptors. PMID- 3340010 TI - Clinical characteristics of diabetic patients with serious pedal infections. AB - The clinical characteristics of 55 diabetic patients referred for treatment of serious pedal infections were surveyed. These patients had been infected for 22.5 +/- 5.0 weeks prior to referral. A majority had received therapy with oral antibiotics and approximately one third had received no antibiotic therapy. The average age of the patients was 53.5 years; average duration of disease, 18 years; and mean weight, 135% of ideal. All had poor glycemic control, as judged by hemoglobin A1c determinations. The patients had a high prevalence of diabetic complications, particularly peripheral neuropathy and nephropathy. Approximately 69% were hypertensive. Although their corrected ESRs were elevated, mean total WBC counts were not. A majority of the patients had zinc deficiency. Most of their infections involved multiple organisms, particularly staphylococcus species, enterococcus, and gram-negative aerobes. These observations suggest that the clinical characteristics of these patients in part explain the difficult nature of their infections and argue the need for early, aggressive antibiotic therapy. PMID- 3340012 TI - U-M Medical Center performs state's first brain graft. PMID- 3340011 TI - Group practice physician study revealing. PMID- 3340013 TI - "Who will touch me today?". PMID- 3340014 TI - A day in the life of a psychiatric nurse. PMID- 3340015 TI - Intensive care nursing in a psychiatric setting. PMID- 3340016 TI - Mental illness and chemical dependency: tough problems for nursing professionals. PMID- 3340017 TI - Who is the nurse working with individuals called "developmentally disabled". PMID- 3340018 TI - "Who am I"? PMID- 3340019 TI - Diabetes in Australia: is the Cinderella of chronic disorders coming of age at last? PMID- 3340020 TI - Women's health needs. PMID- 3340021 TI - Infant feeding--public-health perspective. PMID- 3340022 TI - Infant-feeding practices in Western Australia and Tasmania: a joint survey, 1984 1985. AB - A joint survey of infant-feeding practices that was carried out in Western Australia and Tasmania in 1984-1985 showed a continuing trend back to breast feeding in both States. In Western Australia and Tasmania, 86% and 81% of mothers, respectively, were breast-feeding their babies on hospital discharge. Forty-five per cent of all mothers were still breast-feeding at six months. The social rank of the family had a significant effect on both the prevalence of breast-feeding and on the length of lactation: more mothers in the higher social groups breast-fed their infants, and for longer periods than did mothers of lower social groups. Few infants were introduced to solid foods before three months of age; however, solid and non-milk foods were introduced earlier to infants who were fed artificially than those who were breast-fed. PMID- 3340023 TI - Diabetes in Western Australian children: descriptive epidemiology. AB - The prevalence and incidence of diabetes mellitus in the age group zero to 14 years in Western Australia were determined from a survey by means of Schools Health Services. Additional information from the State's computer-linked hospital records system, the State's only children's hospital, diabetic clinics and physicians enabled virtually complete ascertainment of cases of childhood diabetes. Only 60% of school-age diabetic children were known to school nurses before the survey, but the nurses were able to identify two-thirds of the remainder during the survey. Among non-Aboriginal children, the prevalence of diabetes in the age group zero to 14 years was 0.59 per 1000 children and the incidence was 12.3 per 100,000 children per year. These rates are somewhat lower than those that have been reported from the United Kingdom and North America, and substantially lower than the rates that were reported from Scandinavia. All but one of the diabetic children who were identified required insulin and were assumed to be insulin-dependent. An excess of boys was found. None of 8715 Aboriginal or part-Aboriginal children had insulin-dependent diabetes mellitus, which indicates that this racial group has a low prevalence of this condition. In case--control studies, which used questionnaires for parents, no significant trends were found in relation to the history of immunizations or of specific viral illnesses except for a past history of varicella which was less frequent in diabetic children. A past history of established breast-feeding (of more than one week) was less frequent in diabetic children, as was the ingestion of vitamin C supplements before the onset of diabetes. Some evidence for a seasonality of onset was obtained. The diabetic children were absent from school for more days and had more admissions to hospital than did non-diabetic children. The majority of diabetic children were prescribed insulin twice a day or more often (84%); performed home blood-glucose monitoring (74%); and attended hospital diabetic clinics (91%). PMID- 3340024 TI - Assessing women's health needs. AB - It has been argued that women have specific health needs aside from those of the community as a whole. As a consequence, a move towards increased "earmarked" funding for women's health has occurred. However, some debate exists about the areas of women's health that are most in need of additional funding and about appropriate mechanisms to determine priority areas. The present study explored community perceptions of women's health needs. A sample of 157 women, who had been selected at random, were asked a series of questions about the health and social problems that are experienced by women. The questions assessed the self reported prevalence of the problems and asked women to nominate those problems which were priorities for them personally, and for Australian women in general. The areas that were identified as priorities by this community survey were compared with those that were identified by means of other methods of needs analysis. PMID- 3340025 TI - Frequency of cervical smear-tests among patients of general practitioners. AB - Eight hundred and thirty-eight women who attended 36 general practitioners were asked when they had last undergone a cervical smear-test. Only 6% of women who were between 25 and 54 years of age had never undergone a smear-test, but in women who were younger and older than this age range the proportion was one third. We estimated from this pattern of use of cervical smear-tests that only 60% of invasive cervical cancer is being prevented, and the major contribution to the remaining risk factors comes from women of over 55 years of age who either have not undergone a smear-test or had undergone one a long time previously. This information suggests that general practitioners and the public-health system should be more active in ensuring that all at-risk women undergo cervical smear tests. PMID- 3340026 TI - Continuing medical education. Part 3. Doctors as learners. PMID- 3340027 TI - Hotson's syndrome--the "all-or-nothing" rule. AB - Whenever a plaintiff has lost a chance of a better medical result, which might have been achieved by prompt diagnosis and correct treatment, he or she must recover 100% of the award of damages provided that the plaintiff can prove that he or she had a better than 50% chance of an improved result. PMID- 3340028 TI - Hypercholesterolaemic effect of fish oil in insulin-dependent diabetic patients. AB - The effect of the daily administration of Max EPA fish oil (equivalent to 2.7 g per day of eicosapentaenoic acid) on serum lipid levels was examined in insulin dependent male diabetic patients with cholesterol levels of less than 6.5 mmol/L. After three weeks of fish-oil supplementation there was a significant rise in total cholesterol levels, which was due largely to increases in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)- cholesterol levels. The increase in HDL-cholesterol levels was accounted for by its HDL2 subclass. There was a decrease in serum triglyceride levels, but this was also observed in a control group of diabetic patients who did not receive fish oil and is probably explained by weight loss in this group. Similar changes in lipid levels were found in a subgroup of diabetic patients with retinopathy. The possible detrimental effect of the increase in total cholesterol and LDL-cholesterol levels after Max EPA fish oil at this dose may be offset by the selective rise in the protective HDL2 subclass. PMID- 3340029 TI - Extragenital Mycoplasma hominis infection: a report of two cases. AB - Mycoplasma hominis was isolated from the surgical wounds of two patients. One of these patients developed a septicaemia-like illness after coronary artery vein graft surgery. Mycopl. hominis was isolated from the sternotomy wound and pleural fluid of this patient but not from his blood. No other pathogens were isolated. The second patient developed a low-grade soft-tissue infection due to Mycopl. hominis in a craniotomy wound; his condition responded to tetracycline treatment. The source of infection in both cases presumably was mycoplasmaemia which was secondary to urethral catheterization. Infections due to Mycopl. hominis are overlooked easily unless appropriate steps are taken to isolate and to identify these organisms. PMID- 3340030 TI - Quinidine-induced allergic granulomatous angiitis: an unusual cause of acute renal failure. AB - A case of systemic allergic-type vasculitis after the administration of quinidine and digoxin is described. The renal biopsy findings are unique in that they describe an arteritis with eosinophilic infiltration and non-caseating granulomata. We believe quinidine is the antigen that was responsible for the reported findings. PMID- 3340032 TI - Public opinion on passive smoking. PMID- 3340031 TI - The Australian Tobacco Research Foundation. PMID- 3340034 TI - Placebos and psoriasis. PMID- 3340033 TI - AIDS quiz results: knowledge and risk practices of women attending 24-hour clinics. PMID- 3340035 TI - Training appliance for swallowing difficulties associated with Parkinson's disease: there can be a catch to it. PMID- 3340036 TI - Swallowing disorder in a patient with a cerebrovascular accident. PMID- 3340037 TI - Voluntary euthanasia in The Netherlands. PMID- 3340038 TI - Studies after the isolation of a Legionella-like organism from the air conditioning system of two wards of a hospital. PMID- 3340039 TI - Differential insurance rates. PMID- 3340040 TI - Congenital syphilis--should we worry? PMID- 3340041 TI - Drowning, the sea and life-savers: a clinical audit. PMID- 3340042 TI - Doing it by the rule. PMID- 3340043 TI - Drowning and near-drowning on Australian beaches patrolled by life-savers: a 10 year study, 1973-1983. AB - Resuscitation report-forms of the Surf Life-Saving Association of Australia, for the period 1973-1983, were analysed. During this period there were 262 immersion victims at beaches that were patrolled by life-savers. Of these, 162 victims survived, some of whom received expired-air resuscitation (n = 61) or cardiopulmonary resuscitation (n = 29). Among those who drowned, none was younger than five years of age. Vomiting and regurgitation were major problems during resuscitation. Respiratory and cardiopulmonary arrest occurred after apparently successful rescue; this highlights the necessity for the close observation of victims and the early administration of oxygen to all immersion victims. Resuscitation in deep water has been shown to be effective, and instruction in these techniques is now standard teaching within the Surf Life-Saving Association of Australia. PMID- 3340045 TI - Continuing medical education. Part 4. Evaluation of continuing medical education. PMID- 3340046 TI - Uniform requirements for manuscripts submitted to biomedical journals. International Committee of Medical Journal Editors. PMID- 3340044 TI - Consolidation therapy without maintenance for acute non-lymphoblastic leukaemia. AB - The most effective therapy to prolong remission and to increase cure rates in patients with acute non-lymphoblastic leukaemia is uncertain, and approaches vary from one course of consolidation to two years of maintenance and intensification therapy. We report the results of brief intensive therapy with daunorubicin, cytosine arabinoside and thioguanine, and no maintenance therapy, in 72 patients with a minimum follow-up period of two years. The complete remission rate was 67%, the median duration of remission was 11 months, and 23% of patients whose leukaemias went into remission, have remained in remission for three years and longer. These results are equivalent to those that have been reported with long term chemotherapy. PMID- 3340047 TI - Anorexia tardive: a diagnosis of exclusion? AB - An elderly female patient is described in whom rapid severe weight loss appeared initially to be of psychogenic origin and self-induced. A diagnosis of late-onset anorexia nervosa or anorexia tardive was made when early investigations revealed no abnormality apart from changes that were consistent with malnutrition, and when typical behavioural and psychological factors together with putative psychodynamic issues were revealed. At first, nasogastric feeding was beneficial, but a stormy hospital course ensued. Further investigations revealed the presence of neoplastic disease which at post-mortem examination proved to be small-cell carcinoma of the lung. PMID- 3340048 TI - In-vitro fertilization statistics. PMID- 3340050 TI - Humans and cats have genetically-identical forms of Giardia: evidence of a zoonotic relationship. PMID- 3340049 TI - Low-dose enteric-coated aspirin as an antiplatelet preparation. PMID- 3340052 TI - Opportunistic recall--a plateau. PMID- 3340051 TI - Psychiatric disorders in patients with chronic airways obstruction. PMID- 3340053 TI - Bicentennial measles campaign. PMID- 3340054 TI - Carbon monoxide poisoning: an unusual hazard of a slow-combustion fire. PMID- 3340055 TI - Missed immunization--are doctors to blame? PMID- 3340056 TI - International symposia on nutrition and adolescents: the state of the science. Melbourne, June 19-20 and Brisbane, June 22, 1987. PMID- 3340057 TI - Obesity: risk factors, consequences and control. PMID- 3340058 TI - Assessment and growth. PMID- 3340059 TI - Drugs for parasitic infections. PMID- 3340060 TI - Cytotoxic effects of a leukocidin from Fusobacterium necrophorum on bovine hepatic cells. AB - Cytotoxic effects of a leukocidin from Fusobacterium necrophorum were demonstrated on bovine hepatic cells. The cytotoxic response was dose-dependent and could be inhibited by homologous antiserum. Scanning electron microscopy revealed damaged hepatic cell surface. These findings indicated a pathogenic role of the leukocidin in F. necrophorum infections. PMID- 3340062 TI - Treatment of myelodysplastic syndromes with low-dose oral 6-thioguanine. AB - Several cytotoxic agents when used in vitro in very low concentrations have been shown to induce differentiation of leukemic cells. We treated 18 patients with myelodysplastic syndromes with low-dose oral 6-thioguanine (6-TG; 20 to 60 mg daily). Four patients demonstrated significant improvement in peripheral blood counts. An additional three patients had significant reductions in the percentage of leukemic myeloblasts in the marrow without a corresponding improvement in peripheral counts. With the exception of a fall in the peripheral neutrophil count in four patients requiring dose reductions, no toxicity was observed. Low dose oral 6-TG gives a response rate in myelodysplastic syndromes similar to that of parenteral agents such as cytosine arabinoside. Given the ease of administration and lack of toxicity, oral 6-TG may be a useful treatment modality for these syndromes either alone or in combination with other differentiation enhancing agents. PMID- 3340063 TI - Long-term follow-up of children born to mothers with acute leukemia during pregnancy. AB - Seventeen children born to mothers with acute leukemia who received chemotherapy during pregnancy were examined for physical health, growth, and development. The hematologic and neurologic status and school performance were also evaluated. Chromosomal studies were done in the long-term survivors ranging in age from 4 to 22 years. The children had thorough history and physical examinations to detect any abnormal symptoms or signs. The mothers' previous treatment was documented. In each child growth and development, school performance, intelligence testing, neurologic examination, and hematologic evaluation including bone marrow were normal. Bone marrow cytogenetic studies were also normal. Chemotherapy was given during the pregnancy in each case, including 11 cases during the first trimester. No fetal malformations were found and no late side effects could be demonstrated. The results of this study indicate that pregnancy is not a counterindication for treatment of patients with acute leukemia, and in the cases described here chemotherapy is not associated with excessive risk to the fetus. PMID- 3340061 TI - Salvage chemotherapy for lymphoma with VP-16, ifosfamide, and cisplatin. AB - Between 1983 and 1985, we conducted a phase II clinical trial using VP-16, ifosfamide, and cisplatin (VIP) in patients with refractory lymphoma. Twenty eight patients with bidimensional measurable disease were treated with VP-16 (75 mg/m2), ifosfamide (1.2 g/m2), and cisplatin (20 mg/m2) as daily intravenous infusions for 5 consecutive days. N-Acetylcysteine, 2 g orally every 6 h, was given as a uroepithelial protective agent. All patients had received extensive combination chemotherapy prior to beginning VIP (median number of regimens = 2). Of the 25 patients evaluable for response, 2 patients achieved complete remission and 7 achieved partial remission for an overall objective response rate of 36%. The length of responses ranged from 2 months to 13 months. The predominant toxicity of VIP was myelosuppression. Of 23 patients receiving more than one course of VIP, 17 (73%) had dose reductions or delays related to poor hematologic tolerance of therapy. Uroepithelial and renal toxicity were mild. VIP demonstrates therapeutic activity in refractory lymphoma and appears comparable to other ifosfamide/VP-16 based salvage regimens. PMID- 3340064 TI - Metastatic endodermal sinus tumor of cerebellum and brainstem. PMID- 3340065 TI - Childhood hepatic mesenchymoma: successful treatment with surgery and multiple agent chemotherapy. AB - Malignant undifferentiated sarcoma (mesenchymoma) of the liver is a rare tumor of childhood, with fewer than 100 cases reported in the literature. The overall prognosis for patients with this malignancy is poor. In this report, two children with hepatic mesenchymoma underwent surgical excision followed by 2 years of adjuvant chemotherapy. Rotating cycles of cisplatinum, vincristine/doxorubicin, vincristine/cyclophosphamide, and vincristine/actinomycin D were given with minimal toxicity. Both patients are alive, with no evidence of disease at least 5 years from diagnosis. Previous reports of treatment are reviewed. PMID- 3340066 TI - Bone marrow scanning in Ewing's sarcoma: a clue to histogenesis. PMID- 3340067 TI - ER use by welfare patients. PMID- 3340069 TI - Competitive medicine. A survey of Minnesota physicians. PMID- 3340068 TI - The evolution of Twin Cities hospitals. PMID- 3340070 TI - University hospital. Surviving the 1980s. PMID- 3340071 TI - Is collective bargaining the answer? PMID- 3340072 TI - Maintaining quality in a competitive era. PMID- 3340073 TI - 401(K) plans. Retirement supplements and the new tax law. PMID- 3340074 TI - Taxes and the IRS. PMID- 3340075 TI - Rugged terrain and rough waters: a senator's view of health care. PMID- 3340076 TI - Family Health Plan: a new game in town. PMID- 3340077 TI - Diagnosing appendicitis by computed tomography. PMID- 3340078 TI - Chronic morphine treatment increases cyclic AMP-dependent protein kinase activity in the rat locus coeruleus. AB - We have studied a possible role for cyclic AMP-dependent protein kinase in mediating opiate addiction in the central nervous system by focusing on the rat locus coeruleus. This brain region is well suited for these studies because it is relatively homogeneous and because a wealth of electrophysiological and behavioral data indicate that it plays an important role in mediating the chronic effects of opiates in animals, including humans. It was found that chronic, but not acute, in vivo treatment of rats with morphine increased cyclic AMP-dependent protein kinase activity in the locus coeruleus with a time course that closely paralleled the time course by which locus coeruleus neurons become tolerant to and dependent on opiates, based on electrophysiological studies. Concomitant administration of the opiate receptor antagonist naltrexone was found to block the effect of chronic morphine treatment on protein kinase activity, indicating that the effect is mediated via specific activation of opiate receptors. In contrast, chronic morphine treatment did not alter protein kinase activity in several other brain regions studied, including the neostriatum, frontal cortex, and dorsal raphe. We propose that the observed increase in cyclic AMP-dependent protein kinase activity in the locus coeruleus contributes to the biochemical basis of opiate addiction. PMID- 3340079 TI - Diethyl ether as a substrate for acetone/ethanol-inducible cytochrome P-450 and as an inducer for cytochrome(s) P-450. AB - The ability of diethyl ether to serve as a substrate for microsomal and purified cytochrome P-450 (P-450) and as an inducer for rat hepatic microsomal monooxygenase activities was examined. Microsomal oxidation of ether to acetaldehyde, as monitored by high pressure liquid chromatography, was elevated 3 to 5-fold by treatment of rats with acetone or ethanol, 1.5- to 2-fold by treatment with ether, and only slightly by phenobarbital treatment. Ether also induced N-nitrosodimethylamine demethylase by up to 2-fold and 7-pentoxyresorufin dealkylation by up to 10-fold. These trends agreed with immunoblot experiments in which ether was a weak inducer of the P-450 isozyme IIE1 (encoded by the rat gene P450IIE1), but a stronger inducer of IIB1. A monoclonal antibody against IIE1 inhibited the deethylation by 78% in microsomes from acetone-treated rats and by 45% in controls. N-Nitrosodimethylamine, as well as common inhibitors of IIE1 such as hexane, benzene, pyrazole, and phenylethylamine, strongly inhibited ether deethylation. Using microsomes from acetone-induced rats, the apparent Km for deethylation was 13.4 +/- 2.4 microM and the Vmax was 8.2 +/- 0.2 (nmol of acetaldehyde/min/nmol of P-450). The Km for the controls was 71.3 +/- 9.5 microM. The rates of deethylation at 1 mM ether by purified, reconstituted IIE1 and IIB1 were 4.2 and 0.42 (nmol of acetaldehyde/min/nmol of P-450), respectively. Cytochrome b5 stimulated the rate due to IIE1 apparently by a decrease in the Km. These findings, along with previous work showing marked inhibition by ether of IIE1-dependent reactions, strongly support a major role for this isozyme in ether metabolism. PMID- 3340080 TI - Guanyl nucleotide interactions with dopaminergic binding sites labeled by [3H]spiroperidol in human caudate and putamen: guanyl nucleotides enhance ascorbate-induced lipid peroxidation and cause an apparent loss of high affinity binding sites. AB - The human caudate and putamen contain two high affinity binding sites for [3H]spiroperidol. Both of these affinity states exhibit dopaminergic selectivity. Ascorbic acid, at 0.1 mM, induces a slow loss of the low affinity component of [3H]spiroperidol binding in these tissues. The addition of guanyl nucleotides to the ascorbate produces a more rapid loss of [3H]spiroperidol binding which includes a loss of the highest affinity state for [3H]spiroperidol. Ascorbate induces lipid peroxidation in human caudate and putamen, an effect that is further enhanced by guanyl and inosine nucleotides. In the absence of ascorbate, guanyl nucleotides have no effect on [3H]spiroperidol binding but do decrease the affinity of dopamine at each affinity state greater than 60-fold. In the absence of ascorbate, guanyl nucleotides apparently decrease agonist affinity at human brain dopamine2-binding sites without causing an interconversion of agonist affinity states. PMID- 3340082 TI - Daunomycin-DNA dissociation kinetics. AB - The dissociation of daunomycin from DNA was examined using a sodium dodecyl sulfate-sequestered stopped flow procedure. Two dissociation processes were observed with calf thymus and bacterial DNA, with approximately 45% of the amplitude associated with the faster process. Both processes were largely independent of DNA sequence for bacterial DNA, comprising 30-70% (G + C) content. The rate of both processes increased by a similar amount with increasing ionic strength. The faster process decreased with decreasing drug loading, whereas the slower process was independent of drug loading. Only one dissociation event was observed for the dissociation of daunomycin from four different synthetic polydeoxynucleotides. All observations are consistent with a parallel model of sodium dodecyl sulfate-induced dissociation of daunomycin from DNA, where the two processes observed reflect two resolvable processes that may be comprised of a series of rate constants for the dissociation of drug from differing environments. The slower process observed with bacterial DNA (0.5-0.7 sec-1) is related to dissociation from preferential 5'-CA DNA-binding sites, whereas the faster process reflects dissociation of drug from lower affinity sites on heterogenous DNA (3.2-4.1 sec-1). Dissociation of daunomycin from four different synthetic polydeoxynucleotides (which did not contain the 5'-CA preferential daunomycin-binding site) exhibited dissociation rates characteristic of low affinity sites (3.3-4.8 sec-1). PMID- 3340081 TI - Calcium-dependent regulation of phosphorylase activation in a fast-twitch oxidative-glycolytic skeletal muscle. AB - Calcium-mediated phosphorylase kinase activation has been studied in the rat flexor digitorum brevis, a fast-twitch oxidative-glycolytic skeletal muscle that exhibits a robust inward Ca2+ current [Can J. Physiol. Pharmacol. 63:958-965, 1985]. This system provided an opportunity to compare the regulation of contraction and activation of phosphorylase by extracellular and intracellular sources of Ca2+. In muscles repetitively stimulated at 21 degrees, there appeared to be a close correlation between the control of contraction and phosphorylase activation. Blocking extracellular Ca2+ entry promoted an inactivation of phosphorylase and diminished the elevation of resting tension, which in untreated muscles ensues with the onset of fatigue. The response of muscles stimulated at 37 degrees was in distinct contrast. Phosphorylase, following initial rapid activation, was then briskly inactivated despite the continuation of a near maximal contractile response. An elevation in resting tension during stimulation was observed at 37 degrees but was a transitory response in comparison to what was seen at 21 degrees. Blocking the entry of external Ca2+ inhibited this response. Sarcolemmal Ca2+ channel blockers had no effect on the observed phosphorylase response at 37 degrees, but phosphorylase was already nearly fully inactivated before their effects were manifested on contraction. Thus, at this temperature there is a clear dissociation between Ca2+-mediated regulation of contraction and the production of metabolic energy by enhanced glycogenolysis. This appears to occur because, although Ca2+ induces phosphorylase activation, a subsequent, but rapid non-Ca2+-mediated event promotes inactivation, even while Ca2+-mediated contraction is being sustained. PMID- 3340083 TI - Photoaffinity labeling of human placental monoamine oxidase-A by 4-fluoro-3 nitrophenyl azide. AB - Our previous work has shown that low concentrations of 4-fluoro-3-nitrophenyl azide (FNPA) (0.01-1 microM) photodependently inhibited only the type B monoamine oxidase in rat brain [Biochem. Pharmacol. 34:781-785 (1985)]. Evidence is presented in this paper indicating that higher concentrations of FNPA (15 microM) photodependently inhibit type A monoamine oxidase (MAO-A) from human placenta. FNPA acted as a competitive inhibitor for human placental MAO-A in the dark (Ki = 10 microM) when [14C]serotonin was used as the substrate. The inhibition of MAO-A activity by FNPA was concentration dependent and also irradiation time dependent. The specificity of the photodependent incorporation of FNPA to MAO-A was shown by the protective effect of serotonin during the irradiation. The kinetic analysis showed that the Vmax was decreased whereas the Km was not changed after FNPA was photolyzed with MAO-A. Furthermore, there was no recovery of MAO-A activity upon washing of the photolyzed FNPA-enzyme mixture. These results suggest that FNPA may be covalently bound to the substrate-binding site. Thus, under the present experimental conditions, FNPA is a suitable photoaffinity labeling probe for human placental MAO-A. This is the first photoaffinity label for MAO-A, which may be useful for characterizing the substrate-binding site of this enzyme. PMID- 3340084 TI - Activation of promutagens by plant systems. PMID- 3340085 TI - Promutagen activation by Vicia faba: an assay based on the induction of sister chromatid exchanges in Chinese hamster ovary cells. AB - Plant activation of promutagens was studied using Vicia faba S10 (in vitro activation) and the extracts prepared from promutagen-treated roots of Vicia faba (in vivo activation). The induction of sister-chromatid exchanges in Chinese hamster ovary cells was used as an endpoint to evaluate the cytogenetic effects of promutagens activated by Vicia faba. Cyclophosphamide and ethyl alcohol were activated both by Vicia S10 and by the Vicia extracts, and their activation resulted in an increase in SCEs. Benzo[a]pyrene, 2-aminofluorene, and maleic hydrazide were not activated. Aniline was activated, but without effect on the induction of SCEs. The activation capacity in vitro and in vivo of Vicia faba was not very pronounced, except for the activation of ethyl alcohol, when compared with that of rat-liver S9, and showed differences in activation for the 6 chemical agents tested. PMID- 3340086 TI - The Allium test--an alternative in environmental studies: the relative toxicity of metal ions. AB - Among the test systems suitable for toxicity monitoring, the Allium test (A. cepa) is well known and commonly used in many laboratories. The onions are easy to store and to handle, and the root tip cells constitute a convenient system for macroscopic (growth, EC50 values) as well as for microscopic parameters (c mitosis, stickiness, chromosome breaks). Since the cells possess important plant activation enzymes, the Allium test has a wide area of application. Furthermore, results from the Allium test have shown good agreement with results from other test systems, eukaryotic as well as prokaryotic. A modified version of the test method, comprising series of onions for each concentration of the test liquids, was applied to salts of eight metals: Hg (as methyl mercury chloride (MMC) and as HgCl2), Cu, Ni, Cd, Be, Al (diluted in tap water and distilled water), Mn and Li. The highest toxicity, in EC50 values, was caused by Hg (for MMC 9.0 X 10(-7) M, for HgCl2 3.3 X 10(-6) M), Cu (2.7 X 10(-6) M), Ni (1.7 X 10(-5) M) and Cd (3.1 X 10(-5) M); medium toxicity was caused by Be (4.8 X 10(-4) M) and Al (in tap water 8.0 X 10(-4) M, in distilled water 2.8 X 10(-5) M), and low toxicity by Mn (5.2 X 10(-3) M) and Li (2.0 X 10(-2) M). Some of the metals induced specific microscopic effects, requiring particular mention: thus, Ni treatment induced an unusual form of c-mitosis with the c-mitotic chromosomes remaining on the equatorial plate, Be treatment induced a type of 'banded' or 'fragmented' chromosomes. Treatment with Al led to the development, in the cytoplasm of certain root tip cells, of two oblong hyaline structures formed by material extruded from the nucleus. Chromosome breaks were mainly observed as fragments at mitotic anaphase. The metal ions tested here caused only low amounts of fragments, usually in less than 1% of the cells; only Be caused a higher frequency (4.1%). It was not possible to group the few metals tested here according to their cytological effects. The standard parameters, such as the most commonly occurring c-mitosis or stickiness, showed no correlation to atomic weight or to ion charge of the metals. Still, they gave valuable information in relation to environmental screening; thus, the finding of c-mitosis may indicate risks of aneuploidy. Generally speaking, the Allium test is a very useful tool for evaluating and ranking environmental chemicals with reference to their toxicity. PMID- 3340087 TI - Metabolism of mutagenic polycyclic aromatic hydrocarbons by photosynthetic algal species. AB - Polycyclic aromatic hydrocarbons (PAH) known to produce carcinogenic and mutagenic effects have been shown to contaminate waters, sediments and soils. While it is accepted that metabolites of these compounds are responsible for most of their biological effects in mammals, their metabolism, and to a large extent their bioactivity, in aquatic plants have not been explored. Cultures of photosynthetic algal species were assayed for their ability to metabolize benzo[a]pyrene (BaP), a carcinogenic PAH under conditions which either permitted (white light) or disallowed (gold light) photooxidation of the compound. Growth of Selenastrum capricornutum, a fresh-water green alga, was completely inhibited when incubated in white light with 160 micrograms BaP/l medium. By contrast concentrations at the upper limit of BaP solubility in aqueous medium had no effect on algal growth when gold light was used. BaP quinones and phenol derivatives were found to inhibit growth of Selenastrum under white light incubation. BaP phototoxicity and metabolism were observed to be species specific. All 3 tested species of the order Chlorococcales were growth-inhibited by BaP in white light whereas neither the green alga Chlamydomonas reinhardtii nor a blue-green, a yellow-green or an euglenoid alga responded in this fashion. Assays of radiolabeled BaP metabolism in Selenastrum showed that the majority of radioactivity associated with BaP was found in media as opposed to algal cell pellets, that the extent of metabolism was BaP concentration dependent, and that the proportion of various metabolites detected was a function of the light source. After gold light incubation, BaP diols predominated while after white light treatment at equal BaP concentrations, the 3,6-quinone was found in the highest concentration. Extracted material from algal cell pellets and from media was tested for mutagenicity in a forward mutation suspension assay in Salmonella typhimurium using resistance to 8-azaguanine for selection. Direct-acting mutagens were detected in extracted media from incubation of Selenastrum with 400 micrograms BaP/l for 1 day in gold light. Extracts of media from algae incubated in gold light from 1 to 4 days with 1200 micrograms BaP/l were found to have direct-acting mutagens as well as those requiring further metabolism. Media extracts from white light incubations of BaP were mutagenic upon addition of rat liver homogenates. Activity of these materials from white light treatment are largely attributable to unmetabolized BaP. PMID- 3340088 TI - Chromosomal abnormalities and sister-chromatid exchange in bone marrow cells of mice and Chinese hamsters after inhalation and intraperitoneal administration. II. Cyclophosphamide. AB - The genotoxic effects of cyclophosphamide (CPP), a human and animal carcinogen requiring metabolic activation, were studied in bone marrow cells of mice and Chinese hamsters, analyzing chromosome abnormalities (CA) and sister-chromatid exchange (SCE) after a 2-h inhalation or a single intraperitoneal administration. In order to compare the genotoxicity after the different routes of administration in the dose range of 10-110 mg CPP/kg body weight, the systemic dose obtained by inhalation was calculated from blood concentrations and the inhalation duration after an analysis of the CPP blood kinetics. In NMRI mice the frequency of bone marrow cells with chromosome abnormalities was higher after aerosol exposure than after intraperitoneal administration of comparable CPP doses. In Chinese hamsters the CA frequency was similar with both exposure routes. Inhaled CPP was found to induce a higher frequency of CA and SCE in the bone marrow cells of mice compared to those of Chinese hamsters. The findings suggest that for genotoxins requiring metabolic activation species differences exist with respect to the influence of the route of entry and the sensitivity of bone marrow cells. PMID- 3340089 TI - Biomonitoring of low levels of mercurial derivatives in water and soil by Allium micronucleus assay. AB - The Allium micronucleus (MNC) assay was developed to monitor low levels of mercury in aquatic and terrestrial environments. Four mercurial derivatives namely mercuric chloride (MC), methyl mercuric chloride (MMC), phenyl mercuric acetate (PMA) and a methoxy ethyl mercuric chloride based fungicide, Emisan-6, were tested to assess the sensitivity and versatility of the Allium MNC assay. Allium bulbs were set directly on water and soil contaminated with known levels of mercurial derivatives (0.0001-10.00 ppm). On the 5th day the endpoints measured were root length, mitoses with spindle abnormality and cells with MNC in root meristems. The effective concentrations of the test chemicals that cause 50% of root length as compared to control (EC50) were determined from dose-response curves so obtained. The lowest effective concentration tested (LECT) and highest ineffective concentration tested (HICT) for each of the mercurial derivatives for the induction of spindle malfunction and MNC were determined. It was found that EC50, LECT and HICT values for mercurial derivatives in soil were higher than those in water. The frequencies of cells with MNC and mitoses with spindle abnormality were highly correlated indicating that MNC is a good parameter of spindle malfunction. The present approach increased the sensitivity of the Allium assay by 10-fold, the detection limit being 0.001-0.1 ppm and 0.1-1.0 ppm in aquatic and terrestrial environments respectively, depending on the species of mercury. PMID- 3340090 TI - A non-invasive micronucleus assay in the rat liver. AB - The potent rat-liver mitogen 4-acetylaminofluorene (4AAF) is shown here to provide an effective replacement for the surgical procedure of 2/3 partial hepatectomy (2/3PH) in the in vivo rat-liver micronucleus assay described by Tates and his colleagues. This protocol modification enables the assay to be conducted on a routine basis. Control observations for both 2/3PH and 4AAF treated rats are presented, together with evidence indicating 4AAF itself to be without activity in the assay, irrespective of the mitogenic stimulus. The activities of the rat carcinogens DMN, 2AAF, DMH and 6BT, and of the non carcinogens 4AAF and 4N are demonstrated. Recommendations for the conduct of the modified assay are made. PMID- 3340092 TI - Induction and survival of micronuclei in rat spermatids. Comparison of two meiotic micronucleus techniques using cyclophosphamide. AB - The induction and survival of micronuclei (MN) in rat spermatids was studied by two different methods, the dissection method (DM) and the suspension method (SM). It was observed that MN are induced by cyclophosphamide in the S phase of meiosis, in preleptotene spermatocytes, and in an earlier cell stage, the type B spermatogonia. Both techniques showed that MN survive in spermatids at least 5 days. Advantages of the DM include the use of a DNA-specific fluorochrome for staining of MN, higher MN frequencies observed, and the possibility to gain detailed information of the kinetics of induction of MN. In the SM, slide preparation is simpler than in the DM, and several samples can be prepared simultaneously but the scoring of slides is time consuming. Improvements of the sampling system of the DM are suggested. For evaluation of clastogenic action of chemicals on male germ cells both techniques provide a simple and rapid approach. PMID- 3340091 TI - Preliminary studies on scoring micronuclei by computerised image analysis. AB - Initial studies of the use of computerised image analysis to determine micronucleus frequencies in human lymphocytes that have completed one nuclear division are described. Two methods, based on (a) bromodeoxyuridine incorporation and (b) cytokinesis blocking with cytochalasin-B, were studied. The former method is directly amenable to automation. Cytokinesis-blocked cells could not be automatically recognised by image analysis but it was possible to obtain the correct micronucleus frequency from the integrated optical density histograms by using the mononucleate/binucleate cell ratio obtained by visual analysis. The mean (+/- 1 S.E.) integrated optical density of X-ray-induced micronuclei was 11.2% (+/- 1.1) of that measured for nuclei of G1 cells. PMID- 3340093 TI - The contribution of nitrofluoranthenes and nitropyrenes to the mutagenic activity of ambient particulate organic matter collected in southern California. PMID- 3340094 TI - A new method to reveal the genotoxic effects of N-nitrosodimethylamine in pregnant mice. AB - DNA damage and repair in kidney and liver of mouse fetuses exposed to selected doses of N-nitrosodimethylamine (NDMA) (CAS No. 62.75.9) were studied using the alkaline elution technique. CD1 female mice (15 days pregnant) were treated i.p. with 2 and 10 mg/kg b.w. of NDMA; a slight increase in DNA damage was observed in their fetuses compared to untreated controls. A 2-fold higher extent of DNA damage was induced when mice were treated by intrafetal injections of a rat S9 activating fraction (S9) immediately before exposure to the same dose of NDMA by transplacental means. The DNA-strand breaks disappeared as a function of time in animals treated with NDMA alone. In contrast, a significant persistence of DNA damage was detected in the liver and lung of fetuses which were treated with S9 and NDMA in sequence. These experiments demonstrate the metabolic immaturity of unborn mice as far as the carcinogenic activation of NDMA is concerned and show the high susceptibility of fetal tissues to DNA-damaging agents. The alkaline elution applied in vivo by the transplacental route combined with the intrafetal injection of an exogenous activating microsomal fraction allow to extend our knowledge on the interaction of metabolism-dependent chemicals with fetal tissues. PMID- 3340095 TI - Detection of N-acetyl derivative of 2-amino-6-methyldipyrido[1,2-a:3',2' d]imidazole (Glu-P-1) in Glu-P-1-injected rats. AB - In order to confirm in vivo N-acetylation of 2-amino-6-methyl-dipyrido[1,2 a:3',2'-d]imidazole (Glu-P-1) in rats, we developed a new high-performance liquid chromatography (HPLC) method for detecting the N-acetyl derivative of Glu-P-1 in animal organs. Using this method, N-acetyl-Glu-P-1 was detected in rat liver, kidney and intestinal contents 6 h after intraperitoneal injection of Glu-P-1. This fact provides evidence to support in vivo N-acetylation of Glu-P-1 in rats. PMID- 3340096 TI - Induction of sister-chromatid exchanges by procarcinogens in metabolically competent Chinese hamster epithelial liver cells. AB - An epithelial cell strain has been established from the livers of male Chinese hamsters (CHEL cells). These cells, which proliferate in culture and retain their metabolic enzymatic activities during several subcultures, were used in a sister chromatid exchange assay to evaluate the effectiveness of polycyclic aromatic hydrocarbons (PAHs), aflatoxin B1 (AFB1) and cyclophosphamide (CP). The results obtained demonstrate that CHEL cells are metabolically competent to activate different classes of procarcinogens into biologically active metabolites. Moreover, they showed a selective capacity to discriminate chemical carcinogens from noncarcinogens. Thus, the CHEL cell system appears to be a promising alternative to the short-term tests that include cell-free rodent liver homogenate to evaluate new promutagens and/or procarcinogens. PMID- 3340097 TI - Histoenzymatic profile of human muscle cultured in monolayer and innervated de novo by fetal rat spinal cord. AB - We examined histoenzymatic characteristics of human muscle fibers grown in monolayer culture and innervated de novo in culture for 60-90 days by fetal rat spinal cord neurons. Serial cryostat cross sections were obtained using a freshly frozen sandwich of adult rat muscle and cultured human muscle. An advanced degree of morphologic and histoenzymatic maturation of cultured human muscle was reached after innervation. In contrast to aneurally cultured human muscle fibers, the innervated muscle fibers were smaller in diameter and had myonuclei preferentially located at the periphery of the fiber. The innervated fibers contained a well-developed intermyofibrillar network revealed by the NADH-TR and SDH reactions. Phosphorylase activity was strong to moderate in most muscle fibers. Although most of the innervated cultured muscle fibers were still not fully differentiated into two histochemical fiber types because they had strong ATPase activity after both alkaline and acid preincubation, a few of them had an ATPase profile similar to type 2 fibers in human adult muscle and had reciprocal staining with phosphorylase and NADH-TR reactions. This is the first evidence of differentiation into different histochemical fiber types of human muscle cultured in monolayer and innervated de novo by fetal rat spinal cord. PMID- 3340098 TI - Torpedo monoclonal antibodies react with components of the human peripheral nervous system. AB - A panel of 141 monoclonal antibodies, generated to the Torpedo ray cholinergic nerve terminal preparation, were tested for binding to components of human nerve and muscle. Tested by immunofluorescence, 13 of the antibodies reacted with components of the human intercostal nerve, and 9 bound either muscle or blood vessels in a diversity of staining patterns. Results indicate that the antibodies identify a spectrum of different antigens. Some of the antibodies that cross react with the human nervous system have been studied in the ray and rat. In the human peripheral nerve and muscle, their cytochemical distribution is consistent with what has been observed in these other species. These antibodies, therefore, are likely to identify components of the neuromuscular junction that have been conserved in evolution from elasmobranchs to humans. The antibodies identified here are potentially useful tools for a molecular examination of human nerves and muscles in pathological conditions. PMID- 3340099 TI - Growth of skeletal muscle from patients with amyotrophic lateral sclerosis transplanted into nude mice. AB - We studied the fate of skeletal muscle obtained from patients with amyotrophic lateral sclerosis (ALS) after transplantation into immunodeficient nude mice. The transplanted muscle consistently survived in the nude mice without immunological rejection. The myofibers in these muscles underwent degeneration, followed by regeneration, maturation, and eventual functional innervation by the mouse motor neurons. The ability to grow diseased human muscle successfully over a prolonged period in nude mice offers an in vivo model to study the etiology of ALS and possibly of other neuromuscular disorders. PMID- 3340100 TI - Two types of mitochondrial crystals in diseased human skeletal muscle fibers. AB - Mitochondrial crystalline inclusions, frequently found in mitochondrial myopathies, were analyzed by crystallographic techniques and computer-aided image processing. It could be shown that these structures were real crystals. There are two distinct types of crystal, which can be distinguished by shape, size, and pattern. So-called type I crystals are usually present in the intracristal space, whereas the type II crystals are preferentially located in the intermembrane space between outer and inner mitochondrial membranes. The unit cell dimensions were found to be 38 x 34 x 8 nm for the type I crystals and 20 x 17 x 8 nm for the type II crystals. These results strongly suggest that the crystals are composed of macromolecules, presumably proteins. Arguments are presented that indicate that type I crystals occur only in type 1 muscle fibers and type II crystals in type 2 muscle fibers. PMID- 3340101 TI - Thoracic outlet syndrome surgery causing severe brachial plexopathy. AB - Hundreds of first rib resections are performed yearly in the United States to treat a controversial type of neurogenic thoracic outlet syndrome (NTOS). This surgery was thought to be devoid of serious neurological complications until 1982. However, that year Dale unearthed the rather astounding fact that the members of a single surgical society were aware of nearly 300 brachial plexus injuries resulting in motor deficits that had occurred during such operations, although almost none had been reported in the literature. In this report the features of the two main types of NTOS ("true" and "disputed") are discussed. The history of brachial plexus injury occurring during TOS surgery is traced back to the late nineteenth century. The clinical and electrophysiological features of eight patients who sustained such injuries are described in detail, the literature on this topic is reviewed, and the location and causes for these injuries are discussed. PMID- 3340103 TI - Different rates of long-term motor-nerve stimulation produce different effects on muscle properties. PMID- 3340102 TI - Myoplasmic free [Ca2+] during a malignant hyperthermia episode in swine. AB - Malignant hyperthermia (MH) is a genetic syndrome usually initiated by exposure to volatile anesthetic agents or depolarizing neuromuscular blocking agents. We have used Ca2+-selective microelectrodes to measure in vivo the intracellular ionized calcium ([Ca2+]i) in skeletal muscle fibers of MH-susceptible swines before and during hyperthermic episodes and also after dantrolene administration. The animals were anesthetized with thiopental and fentanyl and maintained with a mixture of nitrous oxide (66%) and oxygen (34%). The malignant hyperthermic episode was triggered by exposure to halothane. Determinations of [Ca2+]i during the episode show an increase from 0.44 +/- 0.01 microM +/- SEM, n = 20) to 8.44 +/- 0.68 microM (mean +/- SEM, n = 10). Administration of dantrolene (2 mg/kg) during the hyperthermic episode reduces [Ca2+]i to 0.17 + 0.01 microM (mean +/- SEM, n = 10) and reverses the clinical symptoms. These results show that the MH episode is associated with an increase in the myoplasmic free Ca2+ concentration and that the therapeutic effect of dantrolene is related to a decrease in [Ca2+]i. PMID- 3340104 TI - Liver disease and common-bile-duct stenosis in cystic fibrosis. AB - To determine the incidence of common-bile-duct lesions and their relation to liver disease in cystic fibrosis, we performed hepatobiliary scanning in 50 of 61 patients with cystic fibrosis who had hepatomegaly, abnormal liver function, or both and in 31 of 92 patients with cystic fibrosis who did not have hepatomegaly or abnormal liver function. Ninety-six percent of the patients with liver disease had evidence of biliary tract obstruction, which was defined cholangiographically as a stricture of the distal common bile duct in the majority of cases. All the patients without liver disease had normal intrahepatic and common-duct excretion of tracer. Abdominal pain was significantly more common in patients with common duct obstruction (P less than 0.001), and enlarged gallbladders occurred only in such patients. Since fasting levels of serum bile acids were elevated in nearly half these patients, irrespective of the severity of their liver disease, serum bile acids may be markers of the severity of the common-duct lesion. We conclude that strictures of the distal common bile duct are common in patients with cystic fibrosis and liver disease. This association requires further study, since surgical relief of common-duct obstruction may prevent or ameliorate the hepatic complications of cystic fibrosis. PMID- 3340105 TI - Pulmonary hazards of smoking marijuana as compared with tobacco. AB - To compare the pulmonary hazards of smoking marijuana and tobacco, we quantified the relative burden to the lung of insoluble particulates (tar) and carbon monoxide from the smoke of similar quantities of marijuana and tobacco. The 15 subjects, all men, had smoked both marijuana and tobacco habitually for at least five years. We measured each subject's blood carboxyhemoglobin level before and after smoking and the amount of tar inhaled and deposited in the respiratory tract from the smoke of single filter-tipped tobacco cigarettes (900 to 1200 mg) and marijuana cigarettes (741 to 985 mg) containing 0.004 percent or 1.24 percent delta 9-tetrahydrocanabinol. As compared with smoking tobacco, smoking marijuana was associated with a nearly fivefold greater increment in the blood carboxyhemoglobin level, an approximately threefold increase in the amount of tar inhaled, and retention in the respiratory tract of one third more inhaled tar (P less than 0.001). Significant differences were also noted in the dynamics of smoking marijuana and tobacco, among them an approximately two-thirds larger puff volume, a one-third greater depth of inhalation, and a fourfold longer breath holding time with marijuana than with tobacco (P less than 0.01). Smoking dynamics and the delivery of tar during marijuana smoking were only slightly influenced by the percentage of tetrahydrocanabinol. We conclude that smoking marijuana, regardless of tetrahydrocannabinol content, results in a substantially greater respiratory burden of carbon monoxide and tar than smoking a similar quantity of tobacco. PMID- 3340106 TI - Falsification of clinical credentials by physicians applying for ambulatory-staff privileges. AB - As part of a quality-assurance program, we reviewed the clinical credentials listed on applications from 773 physicians applying for clinical positions in the Humana MedFirst national ambulatory care program between March 1 and December 31, 1986. In 39 applications (5.0 percent), physicians presented false clinical credentials: 27 physicians (3.5 percent) gave false information about their residency, 10 (1.3 percent) falsely reported board certification, and 2 (0.3 percent) provided false information about both residency and board certification. There was no significant difference between the falsification rates among graduates of U.S. medical schools and those among graduates of foreign medical schools, or among those in the various medical specialties. Falsification was more common among physicians recruited locally than among those recruited nationally, and was significantly more common among applicants who graduated before 1970. Because of this sample included only applicants for ambulatory privileges within a single organization, the findings may be of uncertain generalizability to groups of physicians applying for other classes of privileges in other institutions. We conclude that in applying for some clinical privileges, physicians present inaccurate clinical credentials more frequently than might be expected. PMID- 3340107 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 6-1988. A 36-year-old woman with a past history of pelvic pain and a recent finding of a pelvic mass. PMID- 3340108 TI - Rx for dying: the case for hospice. PMID- 3340109 TI - Screening for HIV. PMID- 3340110 TI - Treatment of cryptococcal meningitis. PMID- 3340111 TI - Ventricular fibrillation complicating myocardial infarction. PMID- 3340112 TI - Insulin resistance in hypertension. PMID- 3340113 TI - Substrate cycling in severe burn injury. PMID- 3340114 TI - Methadone treatment. PMID- 3340115 TI - Teaching safe sex. PMID- 3340116 TI - Shock-wave lithotripsy of gallbladder stones. The first 175 patients. AB - To substantiate the early results of extracorporeal shock-wave fragmentation of gallstones, we used this nonsurgical procedure to treat 175 patients with radiolucent gallbladder calculi. Chenodeoxycholic acid and ursodeoxycholic acid were administered as adjuvant litholytic therapy. The gallstones disintegrated in all patients except one and completely disappeared in 30 percent of all patients within 2 months after lithotripsy, in 48 percent at 2 to 4 months, in 63 percent at 4 to 8 months, in 78 percent at 8 to 12 months, and in 91 percent at 12 to 18 months. In patients with solitary stones up to 20 mm in diameter, the corresponding values were 45, 69, 78, 86, and 95 percent, respectively. Shock wave therapy had no adverse effects except cutaneous petechiae (14 percent) and transient gross hematuria (3 percent). One third of the patients had one or more episodes of biliary colic before all the fragments disappeared. Two patients had mild pancreatitis, which necessitated endoscopic sphincterotomy in one. The patient with insufficient stone fragmentation underwent elective cholecystectomy; no additional operations were necessary. Extracorporeal shock-wave lithotripsy combined with medical therapy for stone dissolution is a safe and effective treatment in selected patients with radiolucent gallbladder calculi. PMID- 3340117 TI - Mechanisms of altered water metabolism in psychotic patients with polydipsia and hyponatremia. AB - Water intoxication is a serious problem in many patients with chronic psychiatric illness. In an effort to determine the mechanism of this disorder, we investigated the osmoregulation of water intake and antidiuretic function in psychiatric patients with polydipsia and hyponatremia and in matched controls with psychiatric illness but neither polydipsia nor hyponatremia. We found that a water load suppressed plasma osmolality and vasopressin and urine osmolality in both groups, but that urinary dilution and free water clearance were impaired in the patients with hyponatremia, even though plasma levels of vasopressin and solute clearance were similar in the two groups. Moreover, during water loading and infusion of hypertonic saline, the plasma level of vasopressin was higher at any given plasma osmolality in the test patients than in the controls, indicating a downward resetting of the osmostat. Patients' estimates of the amount of water they desired were shown to correlate significantly with the amount of water consumed and, at any given level of plasma osmolality, appeared to be higher in the test patients than in the controls. We conclude that psychiatric patients with polydipsia and hyponatremia have unexplained defects in urinary dilution, the osmoregulation of water intake, and the secretion of vasopressin. PMID- 3340118 TI - The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer. AB - Thromboembolic disease has long been recognized as a complication of cancer. Recent reports have suggested that drugs used in the treatment of cancer, including chemotherapeutic agents and hormones, may contribute to this risk, but it has not been possible to separate the effect of these drugs from that of the cancer. We performed a randomized trial comparing 12 weeks of chemohormonal therapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, doxorubicin, and tamoxifen) with 36 weeks of chemotherapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone) in patients with Stage II breast cancer. Among 205 patients randomly assigned to treatment, there were 14 episodes of thrombosis (6.8 percent). These 14 episodes occurred during 979 patient-months of chemotherapy; by comparison, there were no events during 2413 patient-months without therapy. During the first 12 weeks of the study, five patients in the 12-week group and four patients in the 36-week group had thrombosis. During the subsequent 24 weeks, when only patients in the 36-week group were still receiving chemotherapy, there was no thrombosis in the 12-week group, but there were five additional events in the 36-week group (P = 0.03). These findings suggest that chemotherapy contributes to thrombosis in patients with breast cancer. PMID- 3340120 TI - The paradox of health. AB - Although the collective health of the nation has improved dramatically in the past 30 years, surveys reveal declining satisfaction with personal health during the same period. Increasingly, respondents report greater numbers of disturbing somatic symptoms, more disability, and more feelings of general illness. Four factors contribute to the discrepancy between the objective and subjective states of health. First, advances in medical care have lowered the mortality rate of acute infectious diseases, resulting in a comparatively increased prevalence of chronic and degenerative disorders. Second, society's heightened consciousness of health has led to greater self-scrutiny and an amplified awareness of bodily symptoms and feelings of illness. Third, the widespread commercialization of health and the increasing focus on health issues in the media have created a climate of apprehension, insecurity, and alarm about disease. Finally, the progressive medicalization of daily life has brought unrealistic expectations of cure that make untreatable infirmities and unavoidable ailments seem even worse. Physicians should become more aware of these paradoxical consequences of medical progress so that they do not inadvertently contribute to a rising public dissatisfaction with medicine and medical care. PMID- 3340119 TI - Deposition of terminal C5b-9 complement complexes on erythrocytes and leukocytes during cardiopulmonary bypass. AB - Hemolysis, leukopenia, a hemostatic deficit, and nonspecific systemic reactions collectively known as the postperfusion syndrome develop in patients who undergo cardiopulmonary bypass. We now report that terminal C5b-9 complement complexes are deposited on erythrocytes and polymorphonuclear neutrophilic leukocytes during cardiopulmonary bypass. Plasma samples taken from 48 unselected patients during and at the end of cardiopulmonary bypass contained raised levels of fluid phase SC5b-9 complement complexes, indicating that the complement sequence had been activated to completion. Various degrees of overt intravascular hemolysis were observed in all the patients, and lysed erythrocyte membranes were recovered from the blood samples. Immunoassays performed with use of antibodies to C5b-9 neoantigens demonstrated the presence of C5b-9 on red-cell ghosts but not on intact erythrocytes. The appearance of ghosts carrying C5b-9 always coincided with hemolysis. Furthermore, granulocytes isolated from 20 patients during bypass were all found to carry C5b-9 complexes, whereas cells isolated before or 24 hours after surgery carried no C5b-9. The neoantigen-positive material present in detergent extracts of granulocytes sedimented in a broad peak (25 to 40 sedimentation coefficient [S]) in sucrose-density gradients, exactly as did pore forming C5b-9 complexes. Deposition of C5b-9 on blood cells during cardiopulmonary bypass may be partly responsible for the hemolysis and may augment granulocyte activation by the stimulation of arachidonate metabolism in those cells. PMID- 3340121 TI - Psychosis and water balance. PMID- 3340122 TI - Adjuvant therapy for breast cancer. PMID- 3340123 TI - AIDS: politics and science. PMID- 3340125 TI - Exercise and asthma. PMID- 3340124 TI - Obstacles to transplantation technology. PMID- 3340126 TI - Why are today's medical students choosing high-technology specialties over internal medicine? PMID- 3340128 TI - Reduced rate of energy expenditure as a risk factor for body-weight gain. AB - The contribution of reduced energy expenditure to the development of obesity has been a point of controversy. We measured 24-hour energy expenditure (adjusted for body composition, age, and sex), in a respiratory chamber, in 95 southwestern American Indians. Energy expenditure correlated with the rate of change in body weight over a two-year follow-up period (r = -0.39, P less than 0.001). The estimated risk of gaining more than 7.5 kg in body weight was increased fourfold in persons with a low adjusted 24-hour energy expenditure (200 kcal per day below predicted values) as compared with persons with a high 24-hour energy expenditure (200 kcal per day above predicted values; P less than 0.01). In another 126 subjects, the adjusted metabolic rate at rest at the initial visit was also found to predict the gain in body weight over a four-year follow-up period. When the 15 subjects who gained more than 10 kg were compared with the remaining 111 subjects, the initial mean (+/- SD) adjusted metabolic rate at rest was lower in those who gained weight (1694 +/- 103 vs. 1764 +/- 109 kcal per day; P less than 0.02) and increased to 1813 +/- 134 kcal per day (P less than 0.01) after a mean weight gain of 15.7 +/- 5.7 kg. In a group of 94 siblings from 36 families, values for adjusted 24-hour energy expenditure aggregated in families (intraclass correlation = 0.48). We conclude that a low rate of energy expenditure may contribute to the aggregation of obesity in families. PMID- 3340127 TI - Energy expenditure and intake in infants born to lean and overweight mothers. AB - We investigated the contributions of low energy expenditure and high energy intake to excessive weight gain in infants born to overweight mothers. The subjects were infants of 6 lean and 12 overweight mothers, recruited soon after birth. Total energy expenditure and metabolizable energy intake were measured with a new doubly labeled water method over a period of seven days when the infants were 3 months of age, and the postprandial metabolic rate was measured by indirect calorimetry when the infants were 0.1 and 3 months of age. The results were related to weight gain in the first year of life. No significant difference was observed between infants who became overweight by the age of one year (50 percent of infants born to overweight mothers) and those who did not, with respect to weight, length, skinfold thicknesses, metabolic rate at 0.1 and 3 months of age, and metabolizable energy intake at 3 months. However, total energy expenditure at three months of age was 20.7 percent lower in the infants who became overweight than in the other infants (means +/- SE, 256 +/- 27 and 323 +/- 12 kJ per kilogram of body weight per day; P less than 0.05). This difference could account for the mean difference in weight gain. These data suggest that reduced energy expenditure, particularly on physical activity, was an important factor in the rapid weight gain during the first year of life in infants born to overweight mothers. PMID- 3340130 TI - New light on obesity. PMID- 3340129 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 8-1988. A 65-year-old woman with endometrial carcinoma and thrombocytopenia of recent origin. PMID- 3340131 TI - Transfusion-transmitted AIDS reassessed. PMID- 3340132 TI - High-dose steroids and sepsis. PMID- 3340133 TI - Metastatic giant-cell bone tumor in a man positive for HIV. PMID- 3340134 TI - Bone mineral density in medullary thyroid cancer. PMID- 3340135 TI - Antidigoxin antibodies in eclampsia. PMID- 3340136 TI - Legionella prosthetic-valve endocarditis. AB - Since 1982 seven patients at Stanford University Medical Center have been shown to have prosthetic-valve endocarditis caused by Legionella pneumophila or L. dumoffii. We studied the clinical features of legionella endocarditis at the time of diagnosis and performed a case-control study to analyze risk factors for the infection. All patients with endocarditis had a chronic course (3 to 19 months after surgery) of fever, night sweats, weight loss, and anemia, but no embolic events or immune-complex deposition disease. Five patients required surgical replacement of their infected prosthetic valves. The case-control study revealed that during the early postoperative period, patients who later contracted legionella endocarditis were more likely to have had symptoms and signs attributable to postcardiomyotomy syndrome than were patients who did not contract endocarditis (P less than 0.013). Examination of the legionella isolates by means of molecular techniques demonstrated that the Stanford L. pneumophila isolates were genotypically identical to isolates from the hospital drinking water. L. dumoffii isolates from patients with endocarditis were derived from a single strain apparently unique to this medical center. We conclude that legionella infection was nosocomially acquired in the perioperative period. These cases demonstrate an expanding spectrum of illness caused by legionella species and emphasize the need to consider legionella as a cause of "culture-negative" endocarditis. PMID- 3340137 TI - Legionnaires' disease--still with us. PMID- 3340138 TI - Hell's fire and varicella-vaccine safety. PMID- 3340139 TI - More on aluminum, pteridine, and dialysis dementia. PMID- 3340140 TI - Case 37-1987. PMID- 3340141 TI - Health policy agenda for the American people. PMID- 3340142 TI - Buffer's belly. PMID- 3340143 TI - Opticon flutter. PMID- 3340144 TI - Human genome sequence. PMID- 3340145 TI - Competitive elimination of neuromuscular synapses. PMID- 3340146 TI - Sequence patterns in protein kinases. PMID- 3340147 TI - A tissue-specific endothelial cell molecule involved in lymphocyte homing. AB - An endothelial cell surface molecule that is selectively expressed in mucosal organs is required for lymphocyte homing to mucosal lymphoid tissues. This 'vascular addressin' appears to function as a tissue-specific marker or address signal for recognition by lymphocytes circulating in the blood. PMID- 3340148 TI - Neuronal correlate of pictorial short-term memory in the primate temporal cortex. AB - It has been proposed that visual-memory traces are located in the temporal lobes of the cerebral cortex, as electric stimulation of this area in humans results in recall of imagery. Lesions in this area also affect recognition of an object after a delay in both humans and monkeys, indicating a role in short-term memory of images. Single-unit recordings from the temporal cortex have shown that some neurons continue to fire when one of two or four colours are to be remembered temporarily. But neuronal responses selective to specific complex objects, including hands and faces, cease soon after the offset of stimulus presentation. These results led to the question of whether any of these neurons could serve the memory of complex objects. We report here a group of shape-selective neurons in an anterior ventral part of the temporal cortex of monkeys that exhibited sustained activity during the delay period of a visual short-term memory task. The activity was highly selective for the pictorial information to be memorized and was independent of the physical attributes such as size, orientation, colour or position of the object. These observations show that the delay activity represents the short-term memory of the categorized percept of a picture. PMID- 3340149 TI - A complete culture system for the chick embryo. AB - The embryonic lifespan of the chick is 22 days. Development in the first day takes place in the oviduct, and in the remaining 21 days in the shelled egg. There have been few attempts to culture oviductal embryos, though methods covering the first few days of development in ovo are well established and a method for the final 18 days of development through hatching has recently been devised. I have now succeeded in culturing the fertilized ovum of the chick (Gallus domesticus) for the total embryonic period by growing it in a series of separate culture systems. This is the first report of a complete in vitro method for a homoiothermic animal. The technique opens the way to the investigation of developmental events in birds that require access to the embryo at the single cell stage, and in particular to the genetic manipulation of the fertilized ovum. PMID- 3340150 TI - US agencies sift for wheat in 1988 budget chaff. PMID- 3340151 TI - Job losses for cancer scientists at Ludwig institutes. PMID- 3340152 TI - DoE provides funds for human genome sequencing. PMID- 3340153 TI - New AIDS committee in France--the buck stops here? PMID- 3340154 TI - Health risks of radon are given a new look. PMID- 3340155 TI - Embryos sacrosanct. PMID- 3340156 TI - Tonegawa's prize. PMID- 3340157 TI - What was the first living cell? PMID- 3340158 TI - More light on brains. PMID- 3340159 TI - Human vision. Revealing the artist's touch. PMID- 3340160 TI - Three into two won't go. PMID- 3340161 TI - Is there a role for herpesvirus in AIDS? PMID- 3340162 TI - Perception of shape from shading. AB - The human visual system can rapidly and accurately derive the three-dimensional orientation of surfaces by using variations in image intensity alone. This ability to perceive shape from shading is one of the most important yet poorly understood aspects of human vision. Here we present several findings which may help reveal computational mechanisms underlying this ability. First, we find that perception of shape from shading is a global operation which assumes that there is only one light source illuminating the entire visual image. This implies that if two identical objects are viewed simultaneously and illuminated from different angles, then we would be able to perceive three-dimensional shape accurately in only one of them at a time. Second, three-dimensional shapes that are defined exclusively by shading can provide tokens for the perception of apparent motion, suggesting that the motion mechanism is remarkably versatile in the kinds of inputs it can use. Lastly, the occluding edges which delineate an object from its background can also powerfully influence the perception of three-dimensional shape from shading. PMID- 3340163 TI - Real-time imaging of evoked activity in local circuits of the salamander olfactory bulb. AB - The encoding of olfactory information in the central nervous system (CNS) depends on spatially distributed patterns of activity generated simultaneously in many neuronal circuits. Optical neurophysiological recording permits analysis of neural activity non-invasively and with high spatial and temporal resolution. Here, a video method for imaging voltage-sensitive dye fluorescence in vivo is used to map neuronal activity in local circuits of the salamander olfactory bulb. The method permits the imaging of simultaneous ensemble transmembrane activity in real time. After electrical stimulation of the olfactory nerve, activity spreads centripetally from the sites of synaptic input to generate nonhomogeneous response patterns that are presumably mediated by local circuits within the bulbar layers. The results also show the overlapping temporal sequences of activation of cell groups in each layer. The method thus provides high resolution, sequential video images of the spatial and temporal progression of transmembrane events in neuronal circuits after afferent stimulation and offers the opportunity for studying ensemble events in other brain regions. PMID- 3340164 TI - Basic fibroblast growth factor fused to a signal peptide transforms cells. AB - Basic fibroblast growth factor (bFGF) is a potent growth and angiogenic factor that is found in abundance in tissues such as brain, hypothalamus, kidney and cartilage. Despite this copious production of bFGF, most of these tissues are not undergoing either active growth or angiogenesis, suggesting that bFGF activity must be regulated so as to prevent autostimulation of cell growth. In cultured cells, bFGF is associated mainly with cells and basement membranes and is not released into the medium. Prevention of release could be a mechanism for regulation of bFGF activity and may be a consequence of the apparent absence of a secretory-signal sequence in the bFGF protein. Here we investigate whether this regulation can be overridden through the forced secretion of bFGF. Such secretion might provide the bFGF access to its receptor and in turn lead to autocrine transformation of the cell. We report that bFGF, as specified by a recombinant plasmid, is itself unable to induce such transformation, but acquires this ability after fusion with a secretory-signal sequence. The resulting transformants undergo unusual morphological alteration and display tumorigenicity. PMID- 3340165 TI - Origin of the eukaryotic nucleus determined by rate-invariant analysis of rRNA sequences. AB - The origin of the eukaryotic nucleus is difficult to reconstruct. Eukaryotic organelles (chloroplast, mitochondrion) are eubacterial endosymbionts, but the source of nuclear genes has been obscured by multiple nucleotide substitutions. Using evolutionary parsimony, a newly developed rate-invariant treeing algorithm, the eukaryotic ribosomal rRNA genes are shown to have evolved from the eocytes, a group of extremely thermophilic, sulphur-metabolizing, anucleate cells. The deepest bifurcation yet found separates the reconstructed tree into two taxonomic divisions. These are a proto-eukaryotic group (karyotes) and an essentially bacterial one (parkaryotes). Within the precision of the rooting procedure, the tree is not consistent with either the prokaryotic-eukaryotic or the archaebacterial-eubacterial-eukaryotic groupings. It implies that the last common ancestor of extant life, and the early ancestors of eukaryotes, probably lacked nuclei, metabolized sulphur and lived at near-boiling temperatures. PMID- 3340166 TI - Protein biosynthesis in organelles requires misaminoacylation of tRNA. AB - In the course of our studies on transfer RNA involvement in chlorophyll biosynthesis, we have determined the structure of chloroplast glutamate tRNA species. Barley chloroplasts contain in addition to a tRNA(Glu) species at least two other glutamate-accepting tRNAs. We now show that the sequences of these tRNAs differ significantly: they are differentially modified forms of tRNA(Gln) (as judged by their UUG anticodon). These mischarged Glu-tRNA(Gln) species can be converted in crude chloroplast extracts to Gln-tRNA(Gln). This reaction requires a specific amidotransferase and glutamine or asparagine as amide donors. Aminoacylation studies show that chloroplasts, plant and animal mitochondria, as well as cyanobacteria, lack any detectable glutaminyl-tRNA synthetase activity. Therefore, the requirement for glutamine in protein synthesis in these cells and organelles is provided by the conversion of glutamate attached to an 'incorrectly' charged tRNA. A similar situation has been described for several species of Gram-positive bacteria. Thus, it appears that the occurrence of this pathway of Gln-tRNA(Gln) formation is widespread among organisms and is a function conserved during evolution. These findings raise questions about the origin of organelles and about the evolution of the mechanisms maintaining accuracy in protein biosynthesis. PMID- 3340168 TI - Bavarian government maintains reputation for AIDS controversy. PMID- 3340167 TI - Insuring against AIDS. PMID- 3340169 TI - New impetus for French AIDS health education campaign. PMID- 3340170 TI - SmithKline cash for Cambridge. PMID- 3340171 TI - Incidence of leukaemia. PMID- 3340172 TI - Soviet psychiatry. PMID- 3340173 TI - Developmental genetics. Everything you always wanted to know about sex... PMID- 3340174 TI - Scanning tunnelling microscopes. Atomic-scale engineering. PMID- 3340175 TI - How to live with radon. PMID- 3340177 TI - Deleterious mutation and genetic recombination. PMID- 3340176 TI - Diabetes and the potato. PMID- 3340178 TI - Maternal terminology. PMID- 3340179 TI - More on avoiding jet lag. PMID- 3340180 TI - Molecular manipulation using a tunnelling microscope. AB - In a very short time the scanning tunnelling microscope has become an important tool in surface science, and physics in general. Its primary use has been to obtain atomic-resolution images of surfaces, but recently, efforts have been made to use it to manipulate materials as well as image them. One may now reasonably ask if it is possible to move and alter matter predictably on an atomic scale. Here we report the accomplishment of the smallest yet, purposeful, spatially localized changes in matter, effected on a graphite surface. We believe that the changes result from the pinning of individual organic molecules to the graphite. The reverse manipulation, the removal of pinned molecules, has also been demonstrated. Finally, we have evidence that we can remove a portion of a pinned molecule, effectively performing transformations on single molecules using the tunnelling microscope. PMID- 3340181 TI - Absence of interhemispheric connections of area 17 during development in the monkey. AB - Our understanding of the development of cortical connectivity largely stems from studies of the ontogeny of interhemispheric pathways in carnivores, rodents and lagomorphs. Early in development, cortical neurons projecting to the contralateral hemisphere through the corpus callosum (callosal projection neurons) have a widespread distribution. As maturation proceeds, callosal projection neurons become restricted to those cortical regions that are connected in the adult. In newborn cats and rats, for example, callosal projection neurons are not restricted to the 17-18 border as in the adult, but are found throughout areas 17 and 18. The macaque monkey is an exception, because at birth it has an adult-like distribution of callosal projection neurons in area 18, with practically none in area 17. Here we show that whereas area 17 is devoid of interhemispheric connections throughout prenatal development, the distribution of callosal projection neurons in area 18 shows the common sequence of an early widespread distribution followed by regression. The absence of callosal projection neurons in area 17 throughout ontogeny may well be a feature unique to Old World primates. PMID- 3340183 TI - New virus lands in United States. PMID- 3340182 TI - A highly basic histone H4 domain bound to the sharply bent region of nucleosomal DNA. AB - A nucleosomal core particle is composed of two each of histones H2A, H2B, H3 and H4 located inside the particle with approximately 47 base pairs (bp) of DNA wrapped around the octamer in about 1.8 turns of a left-handed superhelix. The path of the superhelix is not smooth; the DNA is sharply bent, or kinked, at positions symmetrically disposed at a distance of about one and four double helical turns in both directions from the nucleosomal dyad axis (designated as sites +/- 1 and +/- 4 respectively). This non-uniform bending is considered archetypal to other DNA-protein complexes, but its mechanism is not clear (reviewed in ref. 4). DNA-histone chemical cross-linking within the core particle has revealed strong binding of each of the two histone H4 molecules to DNA at a distance of 1.5 helical turns either side of the nucleosomal dyad axis (sites +/- 1.5). In each of these sites, a single flexible domain of H4 was previously shown to contact three points, at about nucleotides 55 and 65 on one strand and nucleotide 88 on the complementary strand, numbering from the 5' terminus of each 147-base strand; these three locations are closely juxtaposed across the highly compressed minor and major grooves (Fig. 1). Here we report that the amino-acid residue of histone H4 cross-linked at the 1.5 site is histidine-18, embedded in a highly basic cluster Lys-Arg-His-Arg-Lys-Val-Leu-Arg which is probably involved in the sharp bending of the DNA double helix at the +/- 1 sites. PMID- 3340184 TI - Employee accuses Stanford of health and safety violations. PMID- 3340185 TI - Cancer risk 'slightly higher' for UK nuclear test participants. PMID- 3340186 TI - Pharmacogenetics. Enigmatic variations. PMID- 3340187 TI - Temporal pattern of alcohol dehydrogenase gene transcription reproduced by Drosophila stage-specific embryonic extracts. AB - Regulation of transcription during development has been analysed in vitro using extracts derived from Drosophila embryos. Transcription of mutant templates reveals cis-control regions of the alcohol dehydrogenase promoter responsible for temporal regulation. The activity of a trans-acting protein correlates with the profile of alcohol dehydrogenase expression during embryogenesis. PMID- 3340188 TI - Activation of mitochondrial oxidative metabolism by calcium ions in Limulus ventral photoreceptor. AB - Cells regulate their metabolic energy production to meet the requirements of their energy consuming activities. For most animal cells the prime site of energy production, in the form of ATP, is the mitochondrion. Extensive in vitro studies of isolated mitochondria have provided detailed information about the specific biochemical reactions involved in energy production. At present there is a debate about whether respiration in excitable cells is controlled by the availability of ADP to the mitochondrion and/or by calcium ions. Using the large ventral photoreceptor of the horseshoe crab (Limulus polyphemus) we describe a method for measuring the transient increase in the mitochondrial O2 consumption (delta QO2) following a flash of light of a single photoreceptor. We then show that this delta QO2 results in part from a rise in the intracellular concentration of calcium (Cai). PMID- 3340190 TI - Structural details of an adenine tract that does not cause DNA to bend. AB - Runs of adenines (adenine tracts) have been implicated as the main determinant of sequence-directed DNA bending. The most widely used experimental test for bending relies on the observation that bent DNA migrates more slowly than straight DNA on a polyacrylamide electrophoresis gel. It was shown recently that the polymer (GTTTTAAAAC)n runs with normal mobility on a gel, whereas (GAAAATTTTC)n runs more slowly and thus appears to be strongly bent. The observation that these similar sequences, which differ only in the order of the adenine and thymine tracts, adopt such different shapes offers a stringent test of theories to explain DNA bending. Although the wedge model for DNA bending has recently been elaborated to explain the gel mobilities of these molecules, we wished to determine experimentally the structural basis for the difference in bending. We report here measurements of the frequency of cleavage by the hydroxyl radical at each nucleotide of cloned versions of the two polymers (see Fig. 1). We show that the TTTTAAAA sequence does not display the cleavage pattern that is associated with bent DNA, whereas the AAAATTTT sequence does. The observed sequence dependence of the cleavage pattern of an adenine tract is at odds with current models for DNA bending, which assume that adenine tracts always adopt the same conformation. PMID- 3340189 TI - Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex. AB - Lithium is a unique drug with therapeutic as well as prophylactic value for both manic and depressive phases of manic-depressive illness. The precise mechanisms of its clinical efficacy remain unknown, but there are two main theories of its biochemical action. One proposes that lithium inhibits adrenergically activated adenylate cyclase function whereas the other suggests that it inhibits phosphatidyl inositol turnover, which is known to be activated by cholinergic agonists. Neither mechanism alone, however, can explain both the antimanic and antidepressant effects of lithium. Because of the pivotal role of G proteins in post-receptor information transduction, we have investigated the interaction of lithium with G protein function. Lithium at therapeutically efficacious concentrations completely blocked both adrenergic and cholinergic agonist-induced increases in [3H]GTP binding to membranes from rat cerebral cortex, in both in vitro and ex vivo experiments. The same lithium treatments also abolished guanine nucleotide modulation of agonist binding. Our findings suggest G proteins (Gs and Gi or Go) as the molecular site of action for both the antimanic and antidepressant effects of lithium. PMID- 3340191 TI - Multiple liquid crystal phases of DNA at high concentrations. AB - DNA packaging in vivo is very tight, with volume concentrations approaching 70% w/v in sperm heads, virus capsids and bacterial nucleoids. The packaging mechanisms adopted may be related to the natural tendency of semi-rigid polymers to form liquid crystalline phases in concentrated solutions. We find that DNA forms at least three distinct liquid crystalline phases at concentrations comparable to those in vivo, with phase transitions occurring over relatively narrow ranges of DNA concentration. A weakly birefringent, dynamic, 'precholesteric' mesophase with microscopic textures intermediate between those of a nematic and a true cholesteric phase forms at the lowest concentrations required for phase separation. At slightly higher DNA concentrations, a second mesophase forms which is a strongly birefringent, well-ordered cholesteric phase with a concentration-dependent pitch varying from 2 to 10 micron. At the highest DNA concentrations, a phase forms which is two-dimensionally ordered and resembles smectic phases of thermotropic liquid crystals observed with small molecules. PMID- 3340192 TI - Why sequence the human genome? PMID- 3340193 TI - Move to ban sex determination. PMID- 3340194 TI - National Research Council endorses genome project. PMID- 3340195 TI - Medical merger off. PMID- 3340196 TI - No irradiation yet. PMID- 3340197 TI - AIDS brochure mailing will go ahead in United States. PMID- 3340198 TI - AIDS research centre to be set up in India. PMID- 3340199 TI - Row over vaccine trial. PMID- 3340201 TI - Sex and recombination. PMID- 3340200 TI - Sequence similarities in calcium-binding proteins. PMID- 3340202 TI - Polewards chromosome movement driven by microtubule depolymerization in vitro. AB - We constructed complexes between isolated chromosomes and microtubules made from purified tubulin to study the movement of chromosomes towards the 'minus' end of microtubules in vitro, a process analogous to the movement of chromosomes towards the pole of the spindle at anaphase of mitosis. Our results show that the energy for this movement is derived solely from microtubule depolymerization, and indicate that anaphase movement of chromosomes is both powered and regulated by microtubule depolymerization at the kinetochore. PMID- 3340204 TI - UK health research threatened by "oppressive" new contracts. PMID- 3340203 TI - Growth-controlling molluscan neurons produce the precursor of an insulin-related peptide. AB - Insulin and related peptides are key hormonal integrators of growth and metabolism in vertebrates. There is little biochemical evidence for insulin related peptides in invertebrates, apart from insects for which definitive structural information on these peptides (prothoracicotropic hormone, PTTH) has recently been obtained. We report here the first complete complementary DNA derived primary structure of a preproinsulin-related protein from identified neurons in an invertebrate, the mollusc Lymnaea stagnalis. We have demonstrated by in situ hybridization that transcription of the gene for this molluscan insulin-related peptide (MIP) occurs in the cerebral light-green cells, giant neuroendocrine cells involved in the control of growth, as well as in a pair of neuroendocrine cells called the canopy cells. The insulin-related peptide precursor has the same overall structure as its vertebrate counterparts. The discovery of insulin-related peptides in invertebrates substantiates the evidence for a widespread and early evolutionary origin of the insulin superfamily. PMID- 3340206 TI - New biology centre. PMID- 3340205 TI - Ireland's new biotechnology venture puts marketing first. PMID- 3340207 TI - Californians thinking bigger in neuroscience for the 1990s. PMID- 3340208 TI - Myosin filaments on the move. PMID- 3340209 TI - The molecular nature of the cystic fibrosis antigen. PMID- 3340210 TI - A better way to control pollution. PMID- 3340211 TI - Pattern of covariation between life-history traits of European birds. AB - A large amount of variation is found in most reproductive traits of birds. Clutch size for instance, can vary from 1 to 15 between species of similar body weight. The adaptive significance of this variation is only poorly understood. According to life-history theory, large clutch size and early onset of reproduction are expected when the chances of survival are low. There is some support for the existence of such a relationship from studies of single species. Here I present evidence that, in European birds, clutch size is increased, and onset of reproduction occurs earlier in life, when the probability of survival is low. PMID- 3340212 TI - Evidence for a spectral basis of texture perception in bat sonar. AB - Bats obtain information about the structure of objects in the outside world from their echolocation signals, an extremely useful method when hunting non-flying prey in densely cluttered habitats, for example. Information about object structure is contained both in the time and in the spectral interference patterns of signals reflected from surfaces at different distances from the bat. I report here an experiment designed to test the extent to which bats use these two types of information. A 'phantom target' is generated by playing back to an echolocating bat signals that mimic the result of reflection from two planes set at different distances. The ability of the bat to discriminate between two such targets is investigated as a function of the separations of the planes. Several of the results do not fit the hypothesis that the bat simply uses time-delay information: the very small time difference that can be discriminated, the fall off in ability to discriminate planes at a particular separation and the symmetry of the discrimination ability measured in the frequency domain. The empirical data can best be fitted by a function based on spectral correlation. PMID- 3340213 TI - ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. AB - Antigen-specific cell contacts in the immune system are strengthened by antigen nonspecific interactions, mediated in part by lymphocyte-function associated (LFA) antigens. The LFA-1 antigen is widely expressed on cells of haematopoietic origin and is a major receptor of T cells, B cells and granulocytes. LFA-1 mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by natural killer cells and granulocytes. Recently, ICAM-1 (intercellular adhesion molecule 1) has been defined as a ligand for LFA-1. Monoclonal antibodies to ICAM-1 block T lymphocyte adhesion to fibroblasts and endothelial cells and disrupt the interaction between cytotoxic T cells and target cells. In addition, purified ICAM-1 reconstituted into artificial membranes binds LFA-1+ cells. ICAM-1 is found on leukocytes, fibroblasts, epithelial cells and endothelial cells and its expression is regulated by inflammatory cytokines. LFA-1 has been placed in the integrin family of cell surface receptors by virtue of the high sequence similarity between the LFA-1 and integrin beta chains. The adhesion ligands of the integrin family are glycoproteins bearing the Arg-Gly-Asp (RGD) sequence motif, for example, fibronectin, fibrinogen, vitronectin and von Willebrand factor. Here we show that a complementary DNA clone ICAM-1 contains no RGD motifs, but instead is homologous to the neural cell adhesion molecule NCAM. PMID- 3340214 TI - Expression of the putative Duchenne muscular dystrophy gene in differentiated myogenic cell cultures and in the brain. AB - Duchenne muscular dystrophy (DMD), a sex-linked degenerative disorder of the muscle, is one of the most common lethal genetic diseases in man. It affects about one male in 3,500, with an estimated one-third of cases being caused by new mutations. A less severe disease, Becker's muscular dystrophy (BMD), maps to the same chromosomal locus and is most probably an allelic form of DMD. Both diseases are sometimes associated with various degrees of mental retardation; the molecular basis of these phenotypes is unknown (for review, see ref. 1). The giant DMD gene spans approximately 2,000 kilobases (kb) (0.05% of the human genome) and encodes a 14-kb mRNA. The tissue-specificity of its expression has not been precisely determined. Monaco et al., using Northern blots, reported expression of the gene in human fetal skeletal muscle and small intestine but not in human fetal brain, or in human cultured myoblasts and transformed B and T cells. More recently, expression was detected in mouse skeletal and cardiac muscle, but not in mouse brain. Here we show, using a ribonuclease protection assay, that the DMD gene is developmentally regulated in rat and mouse myogenic cell cultures, and that it is expressed in rat and mouse striated muscle, in mouse smooth muscle and in rat, mouse and rabbit brain. We could not detect transcripts in other non-muscle tissues. PMID- 3340215 TI - Capillary zone electrophoresis-MS. AB - Coupling the separation capabilities of capillary zone electrophoresis with the analytical specificity of mass spectrometry yields a tool for detecting levels of substances down to 10 attomoles. PMID- 3340216 TI - [The patient with situational illness behavior]. PMID- 3340218 TI - [Nothing new in lung cancer?]. PMID- 3340217 TI - [Drugs for the treatment of arterial blood flow disorders]. PMID- 3340219 TI - [The sense of prophylactic treatment of tuberculosis]. PMID- 3340220 TI - [Suicide in 24 European countries, 1972-1984]. PMID- 3340221 TI - [Caroli's disease or congenital cystic dilatation of the intrahepatic bile ducts]. PMID- 3340223 TI - [The treatment of asthma in childhood]. PMID- 3340222 TI - [Caroli's disease confined to one lobe of the liver]. PMID- 3340224 TI - [Smoking and pregnancy, a neglected health problem]. PMID- 3340225 TI - [Acute kidney insufficiency and hypertensive encephalopathy following administration of Baralgin]. PMID- 3340226 TI - [Lithium]. PMID- 3340227 TI - [Possibility of the survival of neonates following a pregnancy of fewer than 26 weeks]. PMID- 3340229 TI - [The motility of the colon]. PMID- 3340228 TI - [The prevention of postoperative lung complications]. PMID- 3340230 TI - [Arthroplasty of the wrist joint using a Swanson silicone rubber prosthesis]. PMID- 3340231 TI - [Acupuncture as a therapeutic method; facts and perspectives]. PMID- 3340232 TI - [Thrombosis of mechanical heart valve prostheses]. PMID- 3340233 TI - [Disobstruction of the carotid artery; a retrospective study]. PMID- 3340234 TI - [Unconsciousness: seizure or not? The importance of the anamnesis in the differential diagnosis of a temporary loss of consciousness]. PMID- 3340235 TI - [Drug treatment of glaucoma]. PMID- 3340236 TI - [Consequences of epilepsy for mother and child and the use of antiepileptic agents in pregnancy]. PMID- 3340237 TI - [Non-steroidal anti-inflammatory drugs and hemorrhage from stomach and duodenal ulcers]. PMID- 3340238 TI - [Normal coronary arteries and yet a heart infarct?]. PMID- 3340239 TI - [Intragastric balloon for the treatment of morbid obesity]. PMID- 3340240 TI - [Treatment of long-term post-spinal puncture headache]. PMID- 3340241 TI - [Headache following lumbar puncture]. PMID- 3340242 TI - [Ophthalmological examination in patients with diabetes mellitus]. PMID- 3340243 TI - [The use of kappa in the study of variability between observers]. PMID- 3340244 TI - [Jumper's knee; an easily treatable sports injury]. PMID- 3340245 TI - [Aspiration cytology in clinical and radiological suspicion of a breast tumor]. PMID- 3340246 TI - [Guided cytological bone puncture in scintigraphically diagnosed skeletal abnormalities]. PMID- 3340247 TI - [Swallowing syncope, a vagovagal reaction]. PMID- 3340248 TI - [The syndrome of painful legs and moving toes]. PMID- 3340249 TI - [Encephalitis in Mycoplasma pneumoniae infections]. PMID- 3340250 TI - [Wilkie's syndrome]. PMID- 3340251 TI - Steroid therapy in IgA nephropathy: a retrospective study in heavy proteinuric cases. AB - 29 patients with IgA nephropathy whose proteinuria persisted at a level of 2.0 g/day or more and who received prednisolone treatment for 1-3 years were retrospectively evaluated on their clinical courses. 13 of 14 patients with renal dysfunction of less than 70 ml/min in initial creatinine clearance (Ccr) values subsequently entered a progressive course during a follow-up period of 47 months, leading to end-stage renal failure in 8 cases. On the other hand, only 1 of the other 15 patients with preserved renal function of 70 ml/min or more ended up with end-stage renal failure during a follow-up period of 74 months, although 7 underwent a progressive course. Three patients in the latter group experienced a prominent reduction in proteinuria to less than 1.0 g/day and maintained renal function. Meanwhile, the steroid group of moderate proteinuric patients with a creatinine clearance greater than 70 ml/min had a benign course, while the nonsteroid group had an unfavorable one. These results suggest that steroid therapy in IgA nephropathy may be able to stabilize a progressive course, especially in the early stage of the disease, although, because they come from an uncontrolled study, a definite conclusion cannot be drawn. PMID- 3340253 TI - Rapid regression of renal medullary granular change during reversal of potassium depletion nephropathy. AB - Structural changes were studied on the kidney of a potassium-depleted man and on rat kidneys during potassium depletion and repletion. Light and electron microscopy revealed rapid disappearance of intracytoplasmic granules in the renomedullary cells after potassium repletion in our patient as well as in rats. In potassium-depleted rats a series of ultrastructural changes, which were similar to those observed in the human kidney were seen with potassium repletion. Most of the granules were reduced in size and number, with loss of internal structure, shrinkage and condensation of their contents, and were almost totally eliminated by 72 h of potassium repletion. In some endothelial and interstitial cells, the granules were seen to be in the process of being extruded through an area of gap in the plasma membrane. The results indicate that most of the intracytoplasmic granules in the renal medulla rapidly disappeared by intracytoplasmic digestion and the rest of them were probably eliminated by exocytosis during reversal of potassium depletion nephropathy in man and rats. PMID- 3340252 TI - Evaluation of vascular calcinosis risk factors in patients on chronic hemodialysis: lack of influence of calcium carbonate. AB - Linear calcifications of the abdominal aorta and of the iliac and femoral arteries were measured yearly for 3 years on X rays of 24 patients on chronic hemodialysis taking variable amounts of calcium carbonate and Al(OH)3 but no pharmacological doses of vitamin D or 1 alpha-hydroxylated vitamin D derivatives. The speed of their extension appeared exponential and covariant with the male sex, age only for men and, independently of these two factors, with diastolic blood pressure and blood triglycerides. Plasma concentrations of calcium, phosphate and glucose were covariant with the extension of calcinosis only at a borderline level. The doses of calcium carbonate and the levels of plasma alkaline phosphatase were not at all covariant. CONCLUSIONS: (1) The effect of high doses of calcium carbonate is possibly harmful only when supraphysiological levels of plasma calcium are induced, whereas plasma phosphate is not adequately decreased. The doses of calcium carbonate per se have no deleterious effect (2). Since alkaline phosphatase is not covariant with the extension of calcinosis, the degree of hyperparathyroidism per se does not seem to play a causative role in vascular calcinosis (3). The main risk factors of vascular calcinosis are: age, the male sex, diastolic blood pressure and blood triglycerides. PMID- 3340254 TI - Dopamine blockade attenuates the natriuresis of saline loading in the adrenalectomized rat. AB - Dopamine blockade with the dopamine-1/dopamine-2 antagonist cis-flupenthixol (CF) attenuates sodium excretion associated with saline loading in both innervated and denervated kidneys of the rat. Blockade of adrenal dopamine-2 receptors prevents the decrease in aldosterone secretion associated with saline loading and may also be responsible for the reduction in sodium excretion induced by CF. Therefore, to determine the role of adrenal dopamine-2 receptors in the attenuated natriuresis induced by CF, the effect of CF or vehicle treatment was examined in two groups of saline-loaded rats 80 (group I) and 120 min (group II) after adrenalectomy. In both groups, CF decreased glomerular filtration rate and sodium excretion after adrenalectomy. It is concluded that dopamine blockade attenuates the natriuresis associated with sodium loading by a direct effect in the kidney. PMID- 3340255 TI - Effect of animal sex on experimental ciclosporin nephrotoxicity. AB - Experimental ciclosporin (CSA) nephrotoxicity is reported to be more severe in male versus female rodents. To investigate these sex differences further, groups of male and female Sprague-Dawley rats were pair fed and given either CSA 50 mg/kg or olive oil vehicle by gavage daily for 5 days. Both groups of treated animals showed azotemia and depression of CIn but there were no sex differences. CSA levels were 5,820 ng/ml in females and 6,480 ng/ml in males (p = NS). Although CSA did not produce enzymuria in either sex, females showed more extensive proximal tubular cell vacuolization. CONCLUSION: Female Sprague-Dawley rats are equally as susceptible to CSA nephrotoxicity as males. Strain differences or experimental design may account for apparently conflicting results in the literature. PMID- 3340256 TI - Aluminum metabolism in rats: effects of vitamin D, dihydrotachysterol, 1,25 dihydroxyvitamin D and phosphate binders. AB - In order to study the effects of vitamin D on aluminium balance when different forms of vitamin D and phosphate binders are used simultaneously for therapeutic purposes, 30 Sprague-Dawley weanling rats, weighing 44-66 g, were randomly assigned to 5 groups: (A) control, (B) aluminum hydroxide, (C) dihydrotachysterol at 16 micrograms/kg/day, (D) 1,25-dihydroxyvitamin D at 16 ng/kg/day and (E) vitamin D at 2,000 IU/kg/day. Aluminum hydroxide (60 mg/kg/day) in the feed was provided to all except the control group. The vitamin D or metabolites were fed by stomach tube daily for a period of 10 days. At the end of the study, the mean (+/- SEM) serum aluminum concentration, as determined by flameless atomic absorption spectrophotometry, was 5.0 +/- 2.4 micrograms/l; there were no significant differences in these results between groups. During the last three days of the study, 24-hour urine and stool collections were made with the usual precautions against trace mineral contamination. The means (+/- SEM) of aluminum balances for groups A, B, C, D and E were -388 +/- 261, 1,121 +/- 331; 2,316 +/- 304; 2,387 +/- 245, and 1,968 +/- 337 micrograms/day, respectively. We conclude that at therapeutic doses of aluminum hydroxide and vitamin D or its metabolites, hyperaluminemia was not observed. However, the positive aluminum balances imply retention, and the use of vitamin D, especially its potent metabolites dihydrotachysterol and 1,25-dihydroxyvitamin D, intensified this risk. PMID- 3340257 TI - Acute oliguria associated with chlorprothixene overdosage. AB - The occurrence of acute reversible oliguria is described in a 23-year-old male after ingestion of 1,500 mg of chlorprothixene in a suicidal attempt. In contrast to earlier reports hypothesizing that the pathophysiology of the renal insufficiency associated with chlorprothixene intoxication may be attributed to direct nephrotoxic effects of the compound or to ischaemia owing to transitory unrecognized shock, a careful diagnostic work-up including renal biopsy, disclosed the presence of acute interstitial nephritis. PMID- 3340259 TI - Erythropoietin in athletes of endurance events. PMID- 3340258 TI - Growth hormone secretion abnormalities in uremic patients: which is the role of impaired glucose hypothalamic sensitivity? PMID- 3340260 TI - Complications with permanent peritoneal dialysis catheters: experience with 154 percutaneously placed catheters. AB - A prospective study evaluated the complications in 154 patients in whom a permanent peritoneal dialysis catheter was inserted percutaneously from April 1982 to June 1986. Obstruction to flow and fluid leakage occurred in 9.2 and 2.6% of the catheters, respectively. Catheter survival was 64.6 and 48.6% at 1- and 2 year follow-up, respectively. The complication rates and survival of percutaneously placed catheters was comparable to those reported for surgically placed catheters. Percutaneous insertion of Tenckhoff catheters is a viable alternative to using the surgical technique. PMID- 3340261 TI - Prevalence of hypouricemia in apparently normal population. PMID- 3340262 TI - Lack of antireticulin and IgA antiendomysium antibodies in sera of patients with primary IgA nephropathy associated with circulating IgA antibodies to gliadin. PMID- 3340263 TI - Lack of relationship between urinary glycosaminoglycans and indices of tubular or glomerular renal damage. Urinary GAG are an unreliable nephrotoxicity index. PMID- 3340265 TI - The cardio-renal syndrome. PMID- 3340266 TI - Comparison of two methods of Tenckhoff catheter insertion. PMID- 3340264 TI - Steroid-responsive nephrotic syndrome with IgA deposits. PMID- 3340267 TI - Survival after brain injury. Cause of death, length of survival, and prognostic variables in a cohort of brain-injured people. AB - Injuries are the leading cause of death in the United States for those between 1 and 44 years of age and brain injuries are a major component of trauma. This report examines survival in a cohort of San Diego County, California, residents who incurred a brain injury in 1981. Cumulative risk of death over time, using the Cox Proportional Hazards Model, and predictors of death (determined by logistic regression) are used to evaluate survival. The results showed that about half of all brain-injured people who died, died in less than 2 h. Severe overall body damage and severe brain injury are the greatest causes of prehospital death. Even if they survived to the hospital, most people who die have brain injury as their underlying cause of death. Age as well as nature and severity of brain injury are the important predictors of in-hospital death. People who are discharged alive from the hospital have survival comparable to that of the population they came from. However, more die from trauma-related causes than would be expected. PMID- 3340268 TI - Evaluation of Parkinson's disease: reliability of three rating scales. AB - We studied the three most commonly used rating scales in Parkinson's Disease (Hoehn and Yahr Clinical Staging, Webster Rating Scale, Columbia University Rating Scale) in order to examine the agreement between observers. Six neurologists, experts at using such scales, evaluated 48 patients suffering from the idiopathic form of Parkinson's Disease. Reliability using the K index was moderate, although a slight superiority was found with the Columbia University Rating Scale. Analysis of the various items used has suggested that scales of disability could be a valid alternative to those examined. PMID- 3340269 TI - Preoptic-hypothalamic pathways controlling nocturnal prolactin surges, pseudopregnancy, and estrous cyclicity in the rat. AB - Frontal, dorsal, or sham deafferentations were placed at various locations within the hypothalamus in order to study the neural pathways involved in pseudopregnancy (PSP), estrous cyclicity, and prolactin (PRL) secretion in the rat. Dorsal or sham transections did not interfere with PSP or estrous cyclicity. Frontal cuts placed on day 3-4 of PSP between the posterior border of the optic chiasm and the anterior tip of the mediobasal hypothalamus (MBH) led to interruption of diestrus within 3-5 days. With frontal cuts placed more caudally in the MBH, and with frontal cuts placed rostrally at the anterochiasmatic area, the duration of PSP was within normal range. Irrespective of their effects on PSP, anterochiasmatic and retrochiasmatic cuts were associated with onset of persistent estrus, and MBH transections resulted in either persistent estrus in some rats or regular estrous cycles in the others. In deafferentated rats that showed persistent estrus, the basal plasma concentrations of PRL measured 3-4 weeks after ovariectomy were 2- to 3-fold higher than in deafferentated and sham deafferentated animals that were cyclic before ovariectomy. Electrical vaginocervical stimulation induced secretion of nocturnal PRL surges in long-term ovariectomized rats with dorsal or sham transections, but not in those bearing frontal cuts, regardless of the neuroanatomical location of the frontal cut. These results suggest that (1) impulses generated at the uterine cervix must reach the medial preoptic area, a putative 'anti-surge center', and proceed from there to the MBH, in order to allow initiation of nocturnal PRL release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3340270 TI - Vasoactive intestinal peptide gene expression from embryos to aging rats. AB - Vasoactive intestinal peptide (VIP) gene transcripts were demonstrated by RNA blot hybridization using VIP-specific RNA hybridization probes. High levels of expression were observed as early as in 16-day-old embryos. In aging rats, the VIP-mRNA levels were reduced significantly (in the cerebral cortex) as compared to 21-day-old rats. Our results suggest a role for the VIP gene protein products during embryonal development. During aging processes the decrease in VIP gene transcripts may be a consequence of either a reduction in the transcriptional activity of VIP neurons or death of VIP-producing cells. PMID- 3340271 TI - Swimming depresses nighttime melatonin content without changing N acetyltransferase activity in the rat pineal gland. AB - Recently, it was shown that a 1.5-ml subcutaneous saline injection depressed N acetyltransferase (NAT) activity and melatonin content in the rat pineal gland at night. The present studies were undertaken to determine if another perturbation, swimming, could duplicate this response. Rats swam at 23.10 h (lights out at 20.00 h) for 10 min and were killed 15 and 30 min after the unset of swimming. Pineal NAT activity was found to be unaffected while melatonin content was depressed dramatically. Hydroxyindole-O-methyltransferase (HIOMT) activity as well as the content of serotonin (5HT), 5-hydroxytryptophan (5HTP) and 5 hydroxyindoleacetic acid (5HIAA) were not changed by this treatment. In a second study, pineal melatonin again was depressed without a concomitant drop in NAT activity. Mean serum melatonin at 15 min after onset of swimming was increased although the rise was not statistically significant. In the final study, it was found that NAT activity was slightly increased in intact rats and unchanged in adrenalectomized rats at 7 min after swimming onset. At 15 min both intact and adrenalectomized animals had NAT activity values similar to those of controls. Pineal melatonin content in intact and adrenalectomized rats plummeted to 50% of control values at 7 min and fell further to 25% at 15 min. While the rate of melatonin synthesis was not directly measured, lack of change in the activities of the enzymes involved in melatonin synthesis and the contents of two melatonin precursors suggests that swimming depresses pineal melatonin content by enhancing melatonin efflux from the gland. PMID- 3340272 TI - Histaminergic mediation of the stress-induced release of prolactin in male rats. AB - Histamine (HA) is likely to participate in the neuroendocrine regulation of prolactin (PRL) secretion. We, therefore, studied the possible involvement of HA in the stress-induced release of PRL in conscious male rats. HA (30 micrograms) infused intracerebroventricularly 15 min before decapitation elevated PRL plasma levels from 5 +/- 1 to 54 +/- 6 ng/ml (p less than 0.01). Intracerebroventricular infusion of the H2 receptor antagonists cimetidine (CIM: 100 micrograms) or ranitidine (RAN: 125 micrograms) abolished the PRL response to HA (p less than 0.01), while intracerebroventricular infusion of the H1 receptor antagonist mepyramine (MEP; 100 micrograms) inhibited the response only 40% (p less than 0.05). Intra-arterial infusion of CIM (2,000 micrograms) or RAN (2,500 micrograms) inhibited the HA-stimulated PRL secretion 52% (p less than 0.01) or 63% (p less than 0.01), respectively. The H1 receptor antagonists MEP (1,000 micrograms) and SKF-93944 (1,500 micrograms) had no effect following intra arterial administration. Restraint stress increased the PRL level to 84 +/- 6 ng/ml (p less than 0.01 vs. control). This effect was prevented by intracerebroventricular infusion of CIM or RAN (p less than 0.01) and inhibited 75% by MEP (p less than 0.01). Intra-arterial infusion of CIM, MEP, and SKF-93944 inhibited the stress response about 50% (p less than 0.01), while RAN decreased the response only 25% (p less than 0.05). Ether stress elevated the plasma PRL concentration to 46 +/- 5 ng/ml (p less than 0.01 vs. control). When infused intracerebroventricularly CIM or RAN prevented the response (p less than 0.01), while MEP had no effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3340274 TI - Activation of 5-HT 1 serotonin receptors in the medial basal hypothalamus stimulates prolactin secretion in the unanaesthetized rat. AB - Prolactin concentrations were measured in plasma in unanaesthetized male rats chronically prepared with venous and intracerebral cannulae, before and after treatment with bilateral intracerebral injections of serotonin and fenfluramine. Serotonin 1, 5, and 10 nmol injected in the medial basal hypothalamus caused dose related rises in prolactin concentrations. The secretion of prolactin was blocked by metergoline (2.5 mg/kg i.p.) and only partially by ketanserin (2.0 mg/kg i.v.). The 5-HT 1A agonist 8-OH-DPAT potently stimulated prolactin at doses of 1 and 5 nmol. Fenfluramine 10 and 100 nmol also caused increases in plasma prolactin when injected in the basal hypothalamus. Prolactin secretion was also evoked by serotonin injections in the preoptic/anterior hypothalamic area, but the response was not blocked by serotonin receptor antagonists. It is concluded that activation of 5-HT 1A receptors on or near prolactin-regulating neurons in the arcuate nucleus causes secretion of prolactin. The effectiveness of fenfluramine in increasing plasma prolactin suggests that endogenous serotonin released from terminals in the basal hypothalamus may mediate prolactin secretion physiologically. PMID- 3340275 TI - Residency programs in neurological surgery United States and Canada. PMID- 3340273 TI - Ether stress stimulates noradrenaline release in the hypothalamic paraventricular nucleus. AB - Differential normal-pulse voltammetry was combined with treated carbon fibre electrodes for monitoring in vivo extracellular catechols synthesized by noradrenergic terminals innervating the paraventricular hypothalamic nucleus. From urethane-anaesthetized rats, pretreated with a monoamine oxidase inhibitor, pargyline, we were able to monitor a catechol signal which unequivocally corresponded to extracellular noradrenaline, and we observed that ether inhalation for 2 min induced an immediate increase in this signal. Electrical stimulation of the ventral noradrenergic pathway (10 Hz for 40 s) induced a similar effect. On the other hand, from freely moving rats which were not treated with pargyline, we recorded a catechol peak which mainly corresponded to 3,4 dihydroxyphenylacetic acid which was synthesized by noradrenergic terminals. However, electrochemical and biochemical evidence strongly suggested that the increase in this signal induced by a 2-min ether stress does not correspond to 3,4-dihydroxyphenylacetic acid, but to an increase in the extracellular noradrenaline concentration. In both experimental situations the time course of the effects was identical: ether stress induced an immediate and pronounced increase in norepinephrine release, and this effect lasted as long as the stimulus duration. This effect appeared specific for noradrenergic terminals, since no effect on dopamine release was observed when recorded from the striatum or behind the paraventricular hypothalamic nucleus from the A13 dopaminergic group. In conclusion, our data are consistent with those which suggest a facilitatory action of norepinephrine on neurosecretory neurons whose cell bodies are located in the paraventricular hypothalamic nucleus and which play a major role in the hormonal response to stress. PMID- 3340276 TI - Magnetic resonance imaging of the optic nerve in optic neuritis. AB - Magnetic resonance imaging (MRI) of the optic nerves using the STIR (short inversion time inversion recovery) sequence was performed in 37 adult patients with a recent or past attack of optic neuritis. MRI revealed high-signal regions in 84% of symptomatic and 20% of asymptomatic nerves. The mean longitudinal extent of lesions was 1 cm. Slow or poor visual recovery was associated with more extensive lesions, or lesions within the optic canal. Disk swelling was usually associated with anterior lesions but also occurred with lesions in the canal. Visual evoked potentials were even more sensitive than MRI in detecting lesions and are still the investigation of choice in suspected demyelinating disease involving the optic nerve. PMID- 3340277 TI - MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. AB - We compared the diagnostic capabilities of MRI to CT, evoked potentials (EP), and CSF oligoclonal banding analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). MRI was the best method for demonstrating dissemination in space. An abnormal appropriate EP in monosymptomatic disease was usually supported by MRI and CSF analysis as being predictive of MS as a clinical diagnosis. A normal appropriate EP study was not satisfactory because MRI and CSF analysis often did not support a diagnosis of non-MS. When there is agreement between three of these paraclinical studies, the diagnosis of MS is probably unequivocal. For use in research studies, laboratory-supported definite MS (LSDMS) could be diagnosed in 85 patients of the total 200 (42.5%), in 19/38 (50%) of optic neuritis (ON) patients, and in 24/52 (46%) of chronic progressive myelopathy (CPM) patients. MRI was 100% successful in identifying patients who qualified for LSDMS in the ON and CPM groups. In a short follow-up (less than 1 year), 19/200 (10%) went on to develop clinically definite MS (CDMS), and MRI predicted that diagnosis in 18/19 (95%). Only long-term follow-up will show how well these studies and the category of LSDMS predict the development of CDMS. The clinical diagnosis of MS (CDMS), even though only 95% accurate, must remain the gold standard. PMID- 3340278 TI - Risk of developing multiple sclerosis after uncomplicated optic neuritis: a long term prospective study. AB - We prospectively studied 60 white patients living in New England who presented with uncomplicated optic neuritis (ON) to determine the risk of developing multiple sclerosis (MS). The diagnoses of ON and MS were made solely on the basis of clinical criteria. Patients were followed for a mean of 14.9 years. Life table analysis indicated that 74% of the women and 34% of the men will have developed MS 15 years after their attack of ON. The risk of developing MS was 3.4 times greater for women than for men. Onset of ON between the ages of 21 and 40 years may have had a modest effect in increasing the risk of developing MS. Recurrence of ON did not appear to affect the risk. PMID- 3340279 TI - Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. AB - In 15 months we encountered eight patients with intracranial tumors who developed erythema multiforme (EM) or erythema multiforme bullosa (Stevens-Johnson syndrome). All occurred shortly after use of phenytoin (DPH) and brain radiation therapy (WBRT). The clinical picture differed from the classic form of EM in that the erythema began on the scalp and spread to the extremities, progressing in three cases to extensive bullous formation. There were no cases of EM among patients who received either DPH or radiotherapy alone. The combination of DPH, WBRT, and tapering of steroids seems to predispose to EM. The pathogenesis of the disorder is probably immunologic. In the absence of seizures, anticonvulsants should not be given routinely to patients with brain tumors. When anticonvulsants are necessary in patients scheduled for WBRT, DPH may not be the drug of choice. PMID- 3340280 TI - 'Crescendo' transient ischemic attacks: clinical and angiographic correlations. AB - Forty-seven consecutive patients presenting acutely with repetitive symptoms indicative of anterior circulation ischemia ("crescendo" transient ischemic attacks) were evaluated to identify clinical features that might reliably predict the presence of significant stenosis, ulceration, or both in the presumably symptomatic internal carotid artery. Angiographic or intraoperative correlation was obtained in all patients, and 26 (55%) were found to have anatomically significant disease. Of 20 patients with signs or symptoms suggestive of cortical ischemia, amaurosis fugax, or both, 17 (85%) had "positive" angiograms; of 18 with numbness/weakness only, 9 (50%) had positive angiograms; of 9 whose symptoms suggested lacunar ischemia, none had positive angiograms. PMID- 3340281 TI - Familial aggregation in Alzheimer's disease: comparison of risk among relatives of early-and late-onset cases, and among male and female relatives in successive generations. AB - Although the morbid risk of Alzheimer's disease (AD) is increased among relatives of AD index cases, it is not yet clear whether the extent of familial aggregation is similar for probands of all ages, or for male and female relatives. The present study investigated the incidence of AD-like illness among 379 first degree relatives of 79 probands in a continuing longitudinal study of AD. Cumulative incidence among relatives increased strikingly with age to 49% by age 87, and the risks observed did not differ appreciably among relatives of presenile-onset versus senile-onset probands. Risks were also similar among parents and sibs. Female relatives appeared to develop the disease earlier than males, but the age-specific risk curves for the two sexes did not differ significantly. These results should not be viewed as direct evidence for dominant genetic transmission of late-onset AD, but they suggest a rationale for formal genetic studies in late-onset (often apparently "sporadic") disease as well as earlier-onset ("familial") cases. PMID- 3340282 TI - Transient global amnesia: characterization of anterograde and retrograde amnesia. AB - Five patients with transient global amnesia (TGA) were given neuropsychological tests during and after their episode. During TGA, all patients were impaired on tests of new learning ability for both verbal and nonverbal material. Retrograde amnesia was patchy and covered a variable period of time before the onset of the episode: from about 36 hours in one case to 4 years in two cases. Some cognitive impairment in addition to amnesia was present during the episode. For example, patients copied a complex figure more poorly during the episode than afterwards. All patients had normal memory at follow-up testing. These data are consistent with the idea that the amnesic symptoms of TGA are caused by transient bilateral dysfunction of medial temporal brain structures important for memory. PMID- 3340283 TI - Migraine stroke. AB - Because the cause of stroke during migraine is not known, we studied 22 (17 females, 5 males; mean age, 32.7 years) classic migraine sufferers who had an ischemic stroke during an attack of migraine, with CT, Doppler ultrasound, cerebral angiography, and two-dimensional echocardiography. We found no cardiac or arterial lesion in 91% of the patients, as compared with 9% of age- and sex matched migraineurs with stroke remote from a migraine attack and 18% of age- and sex-matched nonmigraineurs with stroke (p less than 0.00001). Mitral valve prolapse, arterial dissection, and vasospasm were not significant causes of stroke during migraine. These patients had longer previous attacks of migraine and their infarct was more frequently in the territory involved during the attacks than the controls, supporting the hypothesis that a prolongation of the migrainous process beyond usual limits may explain most migraine strokes. PMID- 3340284 TI - EEG and brain death determination in children. AB - In a retrospective study involving several medical centers we identified 52 patients under age 5 years who met the adult clinical criteria for brain death and had at least one EEG with electrocerebral silence. Of the 52 patients, 31 died spontaneously and 21 were disconnected from the respirator. Repeat EEGs were obtained in 28 patients, and in all electrocerebral silence persisted. The study suggests that clinical criteria similar to those used for adults in the determination of brain death can also be applied to children above age 3 months and that a single EEG with electrocerebral silence is sufficient to confirm brain death in this age group. PMID- 3340285 TI - Evoked potentials in motor system diseases. AB - We studied pattern-shift visual (PSVEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potentials in 38 unselected patients with motor system diseases (MSD) (28 sporadic, 10 familial). PSVEPs were normal in all patients, and BAEPs were normal in all except one with clinical hearing loss who had absent waves I and III and prolonged wave V latencies. Median and tibial SEPs revealed definite CNS conduction abnormalities in only 1 of 30 and 1 of 18 patients, respectively. In addition, four patients had peripheral and four had peripheral or central delays on tibial nerve testing. There were no or only small group differences in central conduction SEP, BAEP, and PSVEP values in patients with normal studies compared with controls. This study suggests that central conduction SEP, BAEP, or PSVEP abnormalities can rarely be attributed to MSD and that their presence in patients suspected of having this disorder should prompt a search for an alternative diagnosis. PMID- 3340286 TI - Inhibition of fatty acid beta oxidation by influenza B virus and salicylic acid in mice: implications for Reye's syndrome. AB - Injection of concentrated influenza B/Lee/40 virus into 4-week-old Balb C mice resulted in 60% inhibition of 14C-palmitate oxidation in isolated hepatic mitochondria. Oral feeding of carnitine to infected mice prevented the inhibition of fatty acid oxidation. High concentrations of salicylic acid given orally also inhibited 14C-palmitate oxidation. Serum free fatty acid concentrations of infected mice and of those fed salicylic acid were significantly higher than in control mice. A combination of low-dose virus and low-dose salicylic acid inhibited palmitate oxidation, suggesting an additive effect on the metabolic derangement when the two agents were present simultaneously. PMID- 3340287 TI - Efficacy of alprazolam for essential tremor. AB - The effect of alprazolam on essential tremor was examined by a double-blind, placebo-controlled parallel study of 24 patients. Results indicated that patients treated with alprazolam had significant improvement in tremor. Transient mild fatigue or sedation in 50% of patients was the primary side effect. Alprazolam may provide therapeutic benefit, especially in patients who require only intermittent therapy. PMID- 3340288 TI - Dopaminergic effects on simple and choice reaction time performance in Parkinson's disease. AB - The present study examined whether premovement central neural processing in Parkinson's disease was related to functional motor disability and plasma L-dopa concentration. Reaction time (RT) performance in simple and choice RT tasks was assessed while plasma L-dopa levels were controlled by continuous IV L-dopa infusion in five parkinsonian patients. Five age-matched controls performed the same RT tasks for comparison. Simple RT for the patients was longer than the normal control RT at all infusion levels (p less than or equal to 0.005). However, choice RT was normal when the patients were "on," but became prolonged as plasma L-dopa levels decreased (p less than or equal to 0.01). The results show that there are abnormalities of premovement central neural processing in Parkinson's disease, and that simple and choice RTs are differentially affected by L-dopa replacement. This suggests that different neural mechanisms may be involved in the processing of these tasks. PMID- 3340289 TI - Azathioprine toxicity during long-term immunosuppression of generalized myasthenia gravis. AB - In this uncontrolled study, 104 patients with generalized myasthenia gravis treated with azathioprine for a median period of 29 months (range, 1 month to 12 years) were surveyed for possible adverse reactions. These occurred in 36 patients (35%) in the following order of frequency: hematologic (18%), gastrointestinal (13%), infectious diseases (13%), and elevation of liver enzymes (6%). No allergic skin reactions were observed. Azathioprine had to be discontinued temporarily in a total of 11 patients (11%) because of possible side effects. The cause of death in the nine patients who died during the period of observation (up to 12 years) was related to myasthenic crisis in two patients. In five patients, a malignant tumor was diagnosed (two carcinoma of the prostate, one ovarian carcinoma, one bronchial carcinoma, and one renal lymphoma) after 2.5 years, 6 months, 3 months, 5 years, and 6 years of treatment, respectively. A causal relationship seems unlikely in the first four cases, but cannot be excluded in the one case of late lymphoma. PMID- 3340290 TI - On the cause of hyporeflexia in the Holmes-Adie syndrome. AB - Electrophysiologic studies were carried out on 11 patients with Holmes-Adie syndrome, 8 of whom had reduced or absent ankle jerks. Conduction velocities and evoked nerve and muscle compound action potentials in the peroneal, posterior tibial, and sural nerves were normal. The H reflex was absent (or virtually absent) in the patients with depressed reflexes. The amplitude of the composite Ia EPSP in single soleus motoneurons was estimated from changes in firing probability of voluntarily activated soleus motor units in response to stimulation of low threshold afferents in the tibial nerve. These amplitudes were used to test the afferent side of the reflex pathway. Composite group Ia EPSPs in Holmes-Aide patients with hyporeflexia were smaller than normal or absent, indicating that the areflexia in the Holmes-Aide syndrome is due to loss of large spindle afferents or reduced effectiveness of their monosynaptic connections to motoneurons. PMID- 3340291 TI - Gracile tract degeneration in patients with sensory neuropathy and AIDS. AB - At autopsy, four homosexual men with acquired immunodeficiency syndrome (AIDS) were found to have selective degeneration of the gracile tract, a finding previously unreported in AIDS. Clinically, these patients had progressive lower extremity paresthesias and dysesthesias with reduced or absent ankle jerks, and eventually they developed dementia. Postmortem examination of spinal cords showed a striking loss of both axons and myelin sheaths confined to the fasciculus gracilis, with the most severe involvement in upper thoracic or cervical segments. Lumbar dorsal columns showed only a mild fiber loss, and no fiber loss was observed in lumbar dorsal roots. Lumbar dorsal root ganglia were available from one patient and showed a mild sensory ganglionitis. In all cases examined, microglial nodules were present in the brain. In 23 other individuals with AIDS who had autopsies consecutively with these four subjects, none had sensory neuropathy and the gracile tracts were normal. The combination of distal sensory neuropathy and gracile tract degeneration suggests a "dying-back" process of dorsal root ganglia neurons. PMID- 3340292 TI - Smooth pursuit dysfunction in Alzheimer's disease. AB - Smooth ocular pursuit was measured by magnetic search coil oculography in 13 patients with Alzheimer's disease and compared with control subjects. Smooth eye movement gain was uniformly reduced in Alzheimer's disease at all target velocities for several frequencies of sinusoidal target motion, signifying impairment of steady-state gain. Normal phase relationships between the target and eyes indicated an intact predictor mechanism for smooth pursuit. When peak target velocity was held constant, pursuit gain decreased markedly in response to small increments of target acceleration, indicating involvement of an acceleration saturating nonlinear element that limits smooth pursuit. Large amplitude saccadic intrusions, in the direction of target motion, often disrupted pursuit; smooth eye movements continued in response to target velocity despite large position errors of the fovea from its target. These disorders of smooth eye movement control can quantify motor dysfunction in Alzheimer's disease. PMID- 3340293 TI - Altitudinal neglect. AB - Previous clinical observations on patients with hemispatial neglect from unilateral hemispheric lesions suggest the brain's attentional mechanisms are organized along the horizontal dimensions of extrapersonal space. We now report a patient with Balint's syndrome caused by bilateral parieto-occipital infarctions, who demonstrated altitudinal neglect. On visual and tactile bisection of vertical rods, the patient consistently placed her mark well above the true midpoint, and this performance remained unchanged when the stimuli were simultaneously explored visually and tactually. She also showed altitudinal inattention in the visual modality by extinguishing the stimulus presented in the lower quadrants during double simultaneous stimulation across the horizontal meridian. These findings suggest that bilateral damage to the parietal lobes can lead to multimodal attentional and exploratory deficits along the vertical dimensions of extrapersonal space. PMID- 3340295 TI - Visual system toxicity following intra-arterial chemotherapy. AB - We studied the effects of intra-arterial chemotherapy on the visual system of 29 consecutive patients with gliomas. As expected, infra-ophthalmic carotid infusion of cisplatin or carmustine (BCNU) was associated with clinically apparent anterior visual pathway lesions. Electroretinography revealed retinal dysfunction in patients without clinical abnormalities. Supra-ophthalmic carotid infusion of cisplatin or BCNU caused no retinal or optic nerve lesions. Electroretinography was abnormal in only one of these patients. Our results indicated that BCNU and cisplatin cause ischemic damage and are toxic to both retinal and neural tissue in patients with gliomas. PMID- 3340294 TI - Hypoglossal, trigeminal, and facial motoneuron involvement in amyotrophic lateral sclerosis. AB - Facial, trigeminal, and hypoglossal motoneuron involvement was quantified in 25 amyotrophic lateral sclerosis patients and in normal controls. Measures included (1) maximum voluntary contraction of the lower lip, mandible, and tongue using custom-designed force transducers, (2) clinical functions of each muscle group, and in some patients (3) orofacial mobility using videofluoroscopy. All measures indicated that the tongue muscles were most severely affected, even in patients who initially had symptoms in the extremities. PMID- 3340296 TI - Expression of three viral oncogenes (v-sis, v-myc, v-fos) in primary human brain tumors of neuroectodermal origin. AB - We determined which viral oncogenes (v-sis, v-myc, and v-fos) were expressed in five primary human brain tumors of neuroectodermal origin (two glioblastomas multiforme, one medulloblastoma, one cystic cerebellar astrocytoma, and one ganglioglioma) and which of these oncogenes is correlated with malignancy. Using the dot hybridization technique, we determined the relative amounts of mRNA coded by these genes using the same nitrocellulose filter. The v-myc probe showed a 4- to 12-fold greater hybridization to the mRNA from two glioblastomas and the medulloblastoma (malignant group) than the mRNA from the cystic cerebellar astrocytoma or the ganglioglioma (benign group). In contrast, RNA hybridizing to v-sis and v-fos were accumulated to a greater extent in the benign tumors. These data suggest that the amount of myc expression may be correlated with the degree of malignancy of brain tumors of neuroectodermal origin. PMID- 3340297 TI - Neuroleptic malignant syndrome: caffeine contracture of single muscle fibers and muscle pathology. AB - The neuroleptic malignant syndrome (NMS) is similar to anesthesia-induced malignant hyperthermia (MH) in three major clinical features: hyperthermia, muscular rigidity, and myoglobinuria. In eight cases of NMS, we studied caffeine contracture of single skinned muscle fibers. Sensitivity of the sarcoplasmic reticulum to caffeine was abnormally increased in six of the eight cases. Morphologic studies showed type 2B fiber atrophy in all six cases examined, and there were necrotic fibers in two cases. Since skeletal muscle is affected in NMS, these patients may be susceptible to MH. PMID- 3340299 TI - Multiple sclerosis: what's in a name? PMID- 3340298 TI - Impairment of masticatory function in hemiplegia. AB - We studied masseter muscle function in 15 hemiplegic patients. Direct motor responses to stimulation of the masseteric nerve were normal. Voluntary activity at maximum strength was reduced on the paretic side. The jaw jerk was symmetric, but facilitation by teeth clenching showed on the nonparetic side only. Masseter silent periods were ill-defined and prolonged in recordings from the paretic side. The second silent period, but not the first, was reduced in size when the paretic side was stimulated, and showed an increased habituation. Though the masticatory nucleus receives bilateral innervation, the contralateral hemisphere exerts a predominant control on voluntary activity and multisynaptic reflexes. PMID- 3340300 TI - Anticoagulation of embolic strokes of cardiac origin: an update. PMID- 3340301 TI - Silent aspiration following stroke. AB - Neurogenic dysphagia following stroke is not limited to brainstem involvement. Among 21 patients with stroke, one-third demonstrated only unilateral signs. In eight patients with silent aspiration, less subjective complaints, weaker cough, and dysphonia occurred more often. Videofluoroscopy must be used liberally in unilateral and bilateral strokes. PMID- 3340302 TI - Unilateral ptosis and Hering's law. AB - In 21 patients with unilateral ptosis, only 1 was found to have lid retraction of the fellow eye--a sign regarded as evidence of Hering's law of equal innervation governing levator function. Hering's law may influence levator function in select cases of ptosis due to disease at or distal to the neuromuscular junction. Alternatively, the relatively autonomous contraction of orbicularis oculi or inhibition of frontalis may mask unilateral lid retraction. PMID- 3340303 TI - Idiopathic CSF pleocytosis in relapsing polychondritis. AB - The association of relapsing polychondritis with CSF pleocytosis is reported for the first time. Three cases are described in which infectious etiologies of the pleocytosis were excluded by appropriate cultures and serologic studies. We suggest that the finding of CSF pleocytosis in relapsing polychondritis does not merit empiric antimicrobial therapy in the absence of demonstrated infection. PMID- 3340304 TI - Familial cavernous angiomas of the brain in an Hispanic family. AB - We found cavernous angiomas (CA) in 10 of 22 members of a large Hispanic family. The proband had seizures, and a CA was found at surgery. He and two sisters with seizures had normal angiograms, but CT or MRI showed lesions compatible with CA. Similar abnormalities were found in two cousins with seizures and 5 of 17 asymptomatic relatives studied. MRI proved to be more sensitive than CT for identifying CA. Hispanic families appear to have a predisposition for dominantly inherited CA of the brain. PMID- 3340305 TI - Deep branch ulnar neuropathy due to giant cell tumor: report of a case. AB - Electrophysiologic studies indicated a lesion of the deep branch of the ulnar nerve in the palm of a 42-year-old man with painless weakness and wasting of ulnar-innervated intrinsic hand muscles. Magnetic resonance imaging of this region demonstrated a soft-tissue mass in the palm distal to Guyon's canal. Surgical exploration disclosed a giant cell tumor of the tendon sheath, compressing the deep branch of the ulnar nerve. PMID- 3340307 TI - Numbness of the tip of the tongue as the presenting symptom of chronic inflammatory polyradiculoneuropathy. PMID- 3340306 TI - Cranial MRI in acute disseminated encephalomyelitis. PMID- 3340308 TI - Charcot and automatisms. PMID- 3340310 TI - Care of the terminally ill. PMID- 3340309 TI - EEG and herpes simplex encephalitis. PMID- 3340311 TI - Visual contrast sensitivity. PMID- 3340312 TI - [Adrenal metastasis: clinical and pathological aspects]. AB - The clinical and autopsy records of 91 patients who died of various malignancies in January 1980-December 1985 were reviewed with regards to metastatic involvement of the adrenal glands. Metastatic involvement was found in 28/91 i.e. 30.7% of all cases, and in 17/30 cases of lung cancer (56.6%). Although in the majority of cases adrenal metastases were associated with widespread metastatic (terminal) disease, thus questioning the utility of clinical surveillance, in 4/17 cases with lung cancer the adrenals were the only visceral site of metastasis. Symptoms were rarely seen and were in all instances aspecific and attributable to the underlying cancer. Early and accurate identification of suprarenal metastasis would, at least in these cases, be a great help in deciding on the therapeutic approach. Unfortunately our ability to diagnose these metastases is somewhat limited partly because the symptoms are few and aspecific, partly because we lack efficient and economical diagnostic techniques. In fact the simpler laboratory techniques cannot identify early metastatic lesions. However assessment of the adrenals should be part of routine staging and restaging procedures in some neoplasias, for the frequency and clinical relevance of these lesions. PMID- 3340313 TI - [Nosocomial infections of the urinary tract in urology patients]. AB - Researches effected in different nations have revealed that 5-12% of all hospitalized patients was affected with a nosocomial infection and that almost 1/3 of these were urinary tract infections. The hospitalized urological patients have a considerable proneness to contract a nosocomial urinary tract infection, because they are subjected to transurethral or suprapubic bladder catheterisms, to transurethral surgery and to the endoscopies, that are promoting maneuvers the urinary tract infections. Generally the Gram negative bacilli are the cause of hospital-acquired urinary tract infections, even if lately Gram positive bacilli (especially Streptococcus Faecalis or Enterococcus), "Gram negative Facultative pathogens" (Klebsiella, Providencia, Citrobacter, Serratia) and Fungi are very important. Considering the importance of these infections we have examined the incidence of the urinary tract infections of the hospitalized patients between January 1, 1986 and December 31, 1986 in our Urologic Institute. During the 12 month study interval there were 450 hospital admissions, and 45 patients were affected with a nosocomial urinary tract infection (10%). The females were affected at the rate of 6.7% of them, with an incidence of 4.7% among all patients with a positive urine culture; on the contrary the males were affected at the rate of 11.4% of them, equal to 19.0% of patients with a positive urine culture. We have noticed that among the responsible microorganisms for the nosocomial urinary tract infections, the group of the "Gram negative Facultative pathogens" was more frequent (40%), followed by Pseudomonas Aeruginosa and Candida species. So also in our Urologic Institute the modification of the responsible agents for the nosocomial urinary tract infections happened. The nosocomial infections after the discovery of the antibiotics were considered wiped out, on the contrary these infections are still an important problem of public health, so that efficaciously must be tackled. PMID- 3340314 TI - [Disorders of heart rhythm during urography studied with Holter monitoring. Comparison of ionic and non-ionic contrast media]. AB - Given the disagreements in the literature over the extent of cardiac complications during urography it was decided to assess any arrhythmias following the injection of ionic and non-ionic contrast media and a placebo by means of 24 hours dynamic Holter monitoring. The results were subjected to meticulous statistical analysis and showed no connection between electrocardiographic alterations and the substance injected. The absence of statistical significance and the variability of the results suggest that alterations in the physiological parameters and/or arrhythmias arising during the administration of contrast media should be assessed with extreme caution. PMID- 3340316 TI - [Hypopotassemia and rhabdomyolysis. Description of 3 cases of different etiologies]. AB - Three cases of rhabdomyolysis secondary to hypopotassaemia caused respectively by excess liquorice intake, the use of a nasal spray containing fluoroprednisolone acetate and a kidney tubular condition identified as distal tubular acidosis (ATR) are described. The aetiology of each case is discussed with a description of the clinical course and laboratory tests and particular emphasis on variations in the renin-angiotensin-aldosterone system. PMID- 3340315 TI - [Continuous EEG monitoring in carotid surgery]. AB - From March 1980 to March 1987, at the Department of Vascular Surgery of the University of Padua, 217 patients underwent 252 carotid revascularizations with routine use of an intraluminal shunt (IS) for symptomatic (70%) or asymptomatic (30%) internal carotid artery (ICA) atherosclerotic stenosis. All carotid endarterectomies (CEs) were routinely performed with patch graft angioplasty to prevent restenosis. In the immediate post-operative period, no patient presented permanent or transient neurological deficits; no patient died. In the early post operative course there was a 0.9% (2 patients) stroke rate and 0.4% (1 patient) mortality rate. These results suggest that the selective use of the IS on the basis of EEG changes is able to reduce the perioperative morbidity and mortality to nearly zero. PMID- 3340317 TI - Immunohistochemical localization of cytochrome P-450 in the rat brain. AB - Immunohistochemical localization of cytochrome P-450 in the brains of normal untreated male rats has been demonstrated with polyclonal antibodies raised against hepatic P-450C. These antibodies recognize P-450C and D, two closely related forms of P-450. We have identified P-450C,D immunoreactivity (P-450C,D-i) within both neurons and glial cells. Neuronal cell bodies showing P-450C,D-i were present in several forebrain areas, including the olfactory bulb, the caudate nucleus, the cingulate, the frontal and the entorhinal cortex, the hippocampus and the thalamus. In the brainstem, P-450C,D-i neurons were detected in the substantia nigra, the nucleus locus coeruleus, raphe nucleus, reticular formation and the trigeminal nerve nucleus and the dorsal motor nucleus of the vagus. Glial cells containing P-450C,D-i were situated within myelinated fiber tracts in the forebrain (e.g. the corpus callosum, the internal capsule) and the brainstem (e.g. the superior cerebellar peduncle, the medial longitudinal fasciculus). Some, but not all, of the P-450C,D-i glial cells also stained with an antibody against glial fibrillary acidic protein. The present findings represent the first immunohistochemical demonstration of cytochrome P-450 in the brain and suggest that cytochrome P-450C,D is constitutive in neurons and glial cells of most brain regions throughout the rat neuraxis. PMID- 3340319 TI - Plasticity of claustroneocortical connections via the corpus callosum in the cat. AB - The cat's distribution of claustral cells that project to the contralateral visual cortex via the corpus callosum was examined. Horseradish peroxidase (HRP) was applied to severed callosal axons to label a heterogeneous population of callosal connections. Cats reared with optically induced strabismus, and Siamese cats, had HRP-filled cells extending more ventrally in the claustrum than in controls. In these groups the compaction of labeled cells was higher than in controls and the amount of increased labeled area was not dependent on the resulting eye alignment. This indicates possible plasticity of visual claustrocallosal connectivity in cats. PMID- 3340318 TI - Immunohistochemistry of choline acetyltransferase in the guinea pig brain. AB - Choline acetyltransferase (ChAT) was localized immunohistochemically within the brain of the guinea pig using a monoclonal antibody. ChAT was found in the cytoplasm of cell bodies and primary dendrites of neurons located in striatum, basal forebrain, cranial nerve motor nuclei and scattered cells in the pons. The greatest numbers of immunoreactive neurons were located in the diagonal band of Broca, medial septum and striatum. Distinct immunoreactive fibers were not visible using this antibody, although a diffuse immunostaining was present in the same nuclear regions as well as in the nerve roots of cranial nerve nuclei and the interpeduncular nuclei. Results of the present study agree closely with other previous reports of acetylcholine distributions. PMID- 3340320 TI - Effect of extracts of injured nerve on initiating the regenerative response in the hypoglossal nucleus in the rat. AB - The uptake of 2-deoxy-[14C]glucose (2-DG) by motor neurons in adult rat hypoglossal nuclei was studied 3 days after subepineural injection of 'crude' soluble protein extracts from intact and injured peripheral nerves into normal hypoglossal nerves. Injured nerve extracts were obtained from 'proximal' and 'distal' segments of sciatic nerves which were transected between two ligatures 3 days earlier. In one group of animals the hypoglossal nerve (experimental) was injected with a particular nerve extract. In another group of animals (control) the hypoglossal nerve was injected with physiological saline solution. Both proximal and distal nerve extracts caused a significant increase in 2-DG uptake. In turn, no 2-DG was detected after treatment with uncut nerve extracts or saline. These findings support the ideas that a substance(s) produced upon nerve injury is taken up by the axons and transported to the cell bodies where it triggers certain metabolic regenerative changes. PMID- 3340321 TI - Norepinephrine is a presynaptic input to visual corpus callosum cells. AB - The neurochemical identity of presynaptic inputs to cell bodies of corpus callosum fibers (callosal cells) located in visual cortex of the cat was investigated using a double labeling technique. Callosal cells were labeled by horseradish peroxidase applied to the severed ends of callosal fibers, and [3H]norepinephrine (NE) was injected into the crown of the lateral gyrus corresponding to the visual cortical area 17/18 border to label synapses. The tissue surrounding the injection sites was processed for electron microscope autoradiography. The results show that NE can be localized to cortical synapses contacting callosal cells in visual cortex of the cat. PMID- 3340322 TI - An autoradiographic study of binding of iodinated spider toxin to lobster muscle. AB - Distribution of the binding sites of Joro spider toxin (JSTX), a specific inhibitor of the glutamate receptors in the crustacean neuromuscular synapse, was studied by using autoradiography. JSTX was synthesized and made radioactive by conjugation with iodine-125. 125I-JSTX irreversibly blocked the excitatory postsynaptic potentials of the lobster neuromuscular synapse in a similar manner as the natural spider toxin. Light microscopic autoradiography of 125I-JSTX treated muscle showed sporadic aggregates of reduced silver grains on the surface of muscles. Electron microscopy of adjoining ultrathin sections revealed that these spots corresponded to the fraction of sarcolemma apposed to axonal terminals with or without synaptic junctional profiles. This finding gives morphological support to the formulation that JSTX binds to the glutamate receptor-ion channel molecules. PMID- 3340323 TI - Ibotenic acid induced demyelination in the central nervous system: a consequence of a local inflammatory response. AB - We examined the effects of injections of ibotenic acid into the medial septum (MS), dorsal lateral geniculate nucleus (dLGN), caudate-putamen (CP) or fornix fimbria (FF) on fibres close to the injection site. Injections into the MS and dLGN resulted in demyelination. The area of demyelination correlated with the area of maximal gliosis. The major cell type in the area of gliosis were cells of haemopoietic origin, as revealed by using monoclonal antibodies (Mabs). Demyelination was not observed in the CP or FF. Axonal transport in fibres en passage through the dLGN lesion was also disrupted following injections of horseradish peroxidase (HRP) into the eye contralateral to the lesion. These results show that when ibotenic acid induces cell death it can secondarily damage myelin sheaths and disrupt axonal transport in areas containing diffuse fibre systems. We suggest that this is due to a non-specific effect of the inflammatory response. PMID- 3340324 TI - A new conditioning paradigm: conditioned limb movements in locomoting decerebrate ferrets. AB - These experiments address the hypothesis that the trajectory of a forelimb in decerebrate ambulating ferrets can be conditioned to avoid an obstacle encountered during the locomotor cycle. The perturbation was produced by interjecting a bar into the trajectory of the forelimb during swing phase. Over 5 15 steps the flexion of the elbow progressively increased until the forelimb was elevated over the bar. Avoiding the bar often required that the maximum height of the paw during swing phase was doubled. When the bar was no longer thrust into the trajectory of the forelimb, the conditioned behavior persisted for several step cycles. The results indicate that decerebrate ferrets are capable of acquiring a conditioned limb movement that is not a typical conditioned reflex but rather an accentuation of a component of the step cycle performed to avoid an interruption of swing phase. PMID- 3340325 TI - Long-duration spike afterhyperpolarizations in neurons from the guinea pig superior cervical ganglion. AB - Intracellular recordings from guinea pig superior cervical ganglia maintained in vitro have revealed a protracted spike afterhyperpolarization in approximately 18% of the principal neurons that is substantially longer (greater than 1 s duration) than those previously reported. This long afterhyperpolarization is distinct from shorter duration afterpotentials in these cells because it can be selectively and reversibly blocked by cooling and by bath applied histamine. Cellular excitability is increased when the long-duration afterhyperpolarization is abolished and thus it deserves consideration as a site for modulation of synaptic transmission through the superior cervical ganglion. PMID- 3340326 TI - Ontogeny and estrogen responsiveness of creatine kinase and glycolytic enzymes in brain and uterus of rat. AB - We have studied the postnatal ontogeny of creatine kinase (CK) and the glycolytic enzymes phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGM), enolase (En), and pyruvate kinase (PK) in rat brain and uterus. In 30-day-old rat, brain and uterus express the fetal isoforms CK-B, PGK-A, PGM-B, En-alpha and PK-M2, and the differentiated isoforms En-gamma and PK-M1. The activity of glycolytic enzymes in uterus of two-day-old rat is as in brain, while CK activity is 3 times higher in brain. The activity of the glycolytic enzymes in brain began to increase (3-4-fold) 10 days after birth, in a coordinated manner. CK activity began to increase 5 days after birth in both brain (4.2-fold) and uterus (4.5 fold), suggesting the dissociation of glycolytic enzyme ontogeny from CK. In contrast to brain, the levels of glycolytic enzymes in uterus were highest at birth, suggesting the action of a tissue-specific mechanism for regulation of the constitutive levels of glycolytic isozymes. Except for PGM, all enzymes showed an increase in total activity, in response to estrogen, in uterus but not in whole brain. PMID- 3340327 TI - Presynaptic M1 muscarinic receptor modulates spontaneous release of acetylcholine from rat basal forebrain slices. AB - Spontaneous release of acetylcholine (ACh) from rat basal forebrain slices in the presence of cholinesterase inhibitor was directly determined using a specific radioimmunoassay for ACh. The release was calcium dependent. A consistent amount of ACh release was observed throughout the experiment. Atropine (10(-8) to 10(-5) M) and pirenzepine (10(-7) to 10(-5) M) enhanced spontaneous ACh release. These findings indicate the presence of an M1 muscarinic autoreceptor that modulates spontaneous release of ACh in the rat basal forebrain. PMID- 3340328 TI - First evidence of cytochrome P-450 induction in the mouse brain by phenytoin. AB - Long-term administration of phenytoin (60 mg/kg) to male C57Bl/6J mice causes an average drug serum level of 16-19 micrograms/ml. Cytological changes consisting of focal axonal swellings in the deep cerebellar nuclei are characterized by an increasing accumulation of vesiculotubular membranes in the dense, but ribosome deficient axoplasm. Microsomal fractions of brain and liver were prepared at intervals until the 80th day of treatment to determine their cytochrome P-450 activities and isoenzyme characteristics. The cerebellar tissue was shown to be distinguished by a 15-fold enhancement of cytochrome P-450 PB3a activity, that means twice the extent of that found in liver and cerebrum. PMID- 3340329 TI - Peripheral effect of fentanyl upon nociception in inflamed tissue of the rat. AB - This study examined a possible peripheral site of action of opiates in the modulation of the response to noxious pressure on inflamed paws. Rats received an injection of Mycobacterium butyricum suspension into one hindpaw which resulted in an ipsilateral inflammatory response (swelling) and decreased threshold to noxious pressure within 1-2 days. Four days post-inoculation direct intraplantar injection of fentanyl resulted in a significant increase of paw pressure thresholds in inflamed, but not in non-inflamed paws. Intraplantar injection of ( )-naloxone but not (+)-naloxone reversed this effect. The action of fentanyl was dose dependent at doses of 0.1-1.2 micrograms. Equal doses of fentanyl given systemically as well as (-)-naloxone or (+)-naloxone given alone were inactive. These data show that fentanyl can modify the response to noxious pressure in inflamed but not non-inflamed paws via a peripheral site of action. Stereospecific reversibility by naloxone as well as dose dependency strongly indicate an opioid mechanism of action. This suggests a possible role for peripherally located opioid receptors in the modulation of nociception in inflamed tissue. PMID- 3340330 TI - Reconsideration of the concept of enhanced static fusimotor drive in rigidity in patients with Parkinson's disease. AB - The electromyographic responses elicited in the first dorsal interosseus muscle by small muscle stretches or by electrical stimulation of the median nerve were investigated in parkinsonian patients and in age-matched healthy subjects. Stimuli were applied during a steady level of contraction in the intrinsic hand muscle. This ensured comparable levels of excitability in the alpha-motoneurone pool in patients and normals. It was found that the normal short-latency stretch reflex was almost absent in rigid patients, while responses to electrical stimulation of low-threshold nerve fibres were of equal size in both groups. This result suggests that there is a change in fusimotor control of muscle spindles in Parkinson's rigidity without alteration of the central gain of the Ia-transmitted stretch reflex. PMID- 3340331 TI - The pursuit of nursing standards. PMID- 3340332 TI - So many models, so much confusion. PMID- 3340333 TI - Nursing diagnosis as a standard: methodology for identifying and validating diagnoses in an ambulatory care setting. PMID- 3340335 TI - The Marker Model for nursing standards: implications for nursing administration. PMID- 3340334 TI - Creating a safer environment for health care workers: implementing a point-of-use sharps disposal system. PMID- 3340336 TI - Using patient outcomes to define nursing practice. PMID- 3340337 TI - Advancing nursing practice: description, recognition, and reward. PMID- 3340338 TI - Who sets nursing standards: the nursing profession or the employment setting? PMID- 3340340 TI - Vitamin E and retinopathy of prematurity. PMID- 3340339 TI - Effects of short-chain fatty acids on a human colon carcinoma cell line. PMID- 3340341 TI - Interaction of elemental diets and chemotherapeutic agents. PMID- 3340342 TI - Alcohol consumption and breast cancer. PMID- 3340343 TI - Posting signs to educate the public. PMID- 3340344 TI - Keeping pelvic examination techniques safe. PMID- 3340345 TI - Assessing the preoperative adult. AB - A patient who is about to undergo surgery requires a presurgery evaluation that focuses on certain risks, including the risk of anesthesia. Even the generally healthy, ambulatory patient who is scheduled for an elective procedure should have a focused history and physical in order to anticipate and prevent complications. This article outlines the questions necessary to ask, the physical examination to be performed and the tests to be ordered during a preanesthesia assessment. PMID- 3340347 TI - [Promotion of mental health: from concept to action]. PMID- 3340346 TI - The nurses and the public. Reflections in a mirror. PMID- 3340348 TI - [Computers in the hospital]. PMID- 3340349 TI - [Breast feeding--between failure and success]. PMID- 3340350 TI - Prevention and health promotion. Has the die already been cast for the nursing profession? PMID- 3340351 TI - Campaigning for the health of Quebecers! PMID- 3340352 TI - [The emergence of self-help groups]. PMID- 3340353 TI - [A contraceptive from Quebec evaluated in Israel]. PMID- 3340355 TI - Tomorrow's nurses. PMID- 3340354 TI - [Supplementary hours--obligatory or not?]. PMID- 3340356 TI - The nurse's image: fact and fiction. PMID- 3340357 TI - Reality of practice for new graduates. PMID- 3340358 TI - Across cultures. PMID- 3340359 TI - Care that wasn't given. PMID- 3340361 TI - Nursing's role in a university rubeola epidemic. PMID- 3340360 TI - Catching up on enrolled nursing. PMID- 3340362 TI - Legal implications of the impaired nurse--Part II. PMID- 3340363 TI - Creative retention and recruitment. PMID- 3340364 TI - A collaborative effort to facilitate role transition from student to registered nurse practitioner. PMID- 3340365 TI - Nursing jobs and satisfaction. PMID- 3340366 TI - Restructuring nursing salaries: a mandate for the future. PMID- 3340367 TI - Clinical ladders for nurses: expect a resurgence of interest but there will be changes. PMID- 3340368 TI - Discretion and professionalization: a correlational study. PMID- 3340369 TI - Recruitment and retention of nurses in critical care. PMID- 3340370 TI - Activating the nursing community: a blueprint for action. PMID- 3340371 TI - Nursing conflict: diagnosis and treatment. PMID- 3340372 TI - How to handle problems on promotion. PMID- 3340373 TI - Toughing it out ... together. PMID- 3340374 TI - Quality of care--its past, present and future. PMID- 3340375 TI - AIDS--a New York view. PMID- 3340376 TI - Teenage pregnancy ... the problem continues. PMID- 3340378 TI - OMPAC. Making politics work for medicine. OSMA Department of Legislation. PMID- 3340377 TI - Legislative forecasts. OSMA Department of Legislation. PMID- 3340379 TI - Snapshots. An ethical look at AIDS. PMID- 3340381 TI - AIDS. Recommendations for preventing transmission of infection with HIV/lymphadenopathy-associated virus during invasive procedures. PMID- 3340380 TI - Treating your practice--II. Making each patient's visit a positive experience. Department of Communications and Physician Marketing. PMID- 3340382 TI - Preventable trauma deaths. PMID- 3340383 TI - Waging a war against cholesterol. PMID- 3340384 TI - Stark County's real-life "Quincy". PMID- 3340385 TI - Student impairment programs: a look around the state. PMID- 3340387 TI - What's new in surgery. PMID- 3340386 TI - AIDS, sex and dope: a reevaluation of ethics and morals. PMID- 3340388 TI - Quality-of-life of cancer patients. AB - During March and April 1986 a study of the quality-of-life of cancer patients was done in a medical school-affiliated community hospital in the Midwest, USA. The control group was that of a family practitioner. The experimental group was composed of only those suffering from oncological diseases and the control group of only those without cancer. Ninety-eight experimental patients were studied during 293 visits as were 112 controls during 137 visits. The study instrument was a linear analogue scale of 10 items. Patients were scored from 0 to 10 on each item and then the median, mean, span, and standard deviation were calculated. The means were compared. Overall the control group scored on average 6.67; the experimental group 6.06. This was statistically significant. Subgroups of each practice were then compared with each other, and subgroups of the oncological patients were compared with each other. In general, women in the experimental group did not differ significantly from women in the control group, while men related that they were doing more poorly than did men in the control group and women in the experimental arm. An analysis of exactly where men did worse is made. Lastly, an informed, experienced laywoman attempted to blindly predict, within one point, the scores some consecutive experimental patients would make on their test. She was unable to do this more than 20% of the time. PMID- 3340389 TI - Prolonged fever as a presenting symptom in adrenal tumors. AB - Four patients with adrenal tumors in whom prolonged fever was the foremost symptom are presented. Two of the patients had nonfunctional adrenocortical carcinoma, one had a pheochromocytoma without adrenergic hyperactivity, and in the fourth, an aldosteronoma was found. Only in 1 case was the tumor (pheochromocytoma) resectable and this patient became afebrile post surgery. A review of the literature revealed that fever is encountered in 6-10% of cases with adrenal tumors, sometimes as the first manifestation of disease. However, a survey of the large series of fever of unknown origin revealed no mention of adrenal tumors in that group of solid tumors which many cause prolonged fever. PMID- 3340390 TI - Infiltration of Leu-3a+3b-positive lymphocytes and expression of human leukocyte antigen DR on tumor tissue induced by radiation therapy. AB - Tumor infiltrating lymphocytes induced by radiotherapy were analyzed by the biotin-avidin-horseradish peroxidase method. At the early dose of 4 Gy (400 rad) of irradiation (2 Gy X 2), remarkable infiltration of lymphocytes was observed surrounding cancer cells. This infiltration was mainly composed of Leu-3a+3b positive lymphocytes, and human leukocyte antigen DR-positive tumor and interstitial cells were remarkably observed. PMID- 3340391 TI - VP-16-based regimen in adult acute nonlymphoblastic leukemia. AB - A new VP-16-based drug combination was utilized in the treatment of 3 adult patients with acute nonlymphoblastic leukemia. Marrow aplasia was noted in all patients on day 7. While myeloid regeneration was noted on day 14, there was no evidence of regeneration of the erythroid series before day 21 in any of the 3 patients, and maturation of this cell line was never complete before day 35. Such prolonged suppression of the erythroid series has not been described with standard chemotherapy. Because of this protracted suppressive effect of the above regimen on erythroid cells, we propose to explore its therapeutic potential in a pilot study employing such a regimen in the treatment of erythroleukemia. PMID- 3340392 TI - Comparison of photodynamic inactivation of experimental stomach tumors sensitized by acridine orange or hematoporphyrin derivatives. AB - The photodynamic inactivations of Walker carcinosarcoma 256 stomach tumors by the concomitant use of acridine orange (AO) and argon laser, and by the combined use of hematoporphyrin derivatives (HPD) and dye laser were compared. Wistar rats bearing stomach tumors of 4-6 mm in diameter 5-10 days after their implantation were injected intraperitoneally with 40 mg/kg body weight of AO or HPD, and 24 h later their stomach tumors were exposed to argon laser at 488 nm or dye laser at 630 nm, respectively, at an intensity of 15 mW/cm2 for 20 min. Temperature rise was less than 3 degrees C during irradiation. Seven days after irradiation, complete or partial necrosis with sparing of the surrounding mucosa was seen histologically in all rats treated by the two therapy methods. Phase contrast and electron microscopy showed nuclear pyknosis and damage to the inner layer of the nuclear envelope in tumor cells treated with AO and argon laser, while cytotoxicity involved damage to the outer layer of the nuclear envelope and intracytoplasmic organelles in tumor cells treated with HPD and dye laser. This difference between AO and HPD is considered to be a difference in their intracellular localization in tumor cells. PMID- 3340393 TI - Protective effects of a prophylactic treatment with the bisphosphonate 3-amino-1 hydroxypropane-1,1-bisphosphonic acid on the development of tumor osteopathies in the rat: experimental studies with the Walker carcinosarcoma 256. AB - The present report primarily describes protective effects of a long-term prophylactic treatment with 3-amino-1-hydroxypropane-1,1-bisphosphonic acid (APD) on the development of tumor-induced osteolytic bone destructions. Pretreatment with daily intravenous doses of APD 9.5 mg/kg for 1 week resulted in a significant reduction of Walker carcinosarcoma 256-induced bone destruction, when Walker cells were transplanted intraosseously (2 x 10(6) tumor cells/rat) 7 weeks later. Shorter pretreatment periods (4, 2 or 1 week prior to tumor inocculation) resulted in a nearly total inhibition of bone destruction as well as tumor induced hypercalcemia. Tumor growth itself was not inhibited by APD pretreatment. Histological and microradiographical findings are reported. Consistent to our experiments and with regard to new immunocytological methods to detect single metastatic tumor cells in the bone marrow, potential risk groups may be defined which may profit from the prophylactic APD treatment to inhibit tumor-induced bone destructions. PMID- 3340394 TI - Induction of neoplasms in the Egyptian toad Bufo regularis by gibberellin A3. AB - Force feeding the Egyptian toads (Bufo regularis) with gibberellin A3 (10 ppm) twice a week for 5 months induced neoplasms in 8 out of 50 (16%) experimental animals. Primary tumours developed in the liver (hepatocellular carcinomas). Two secondary tumours in the kidneys and another 2 in the ovaries of toads developed due to metastases from the hepatocellular carcinomas. The results show that gibberellic acid (gibberellin A3) has a carcinogenic effect in the Egyptian toads. PMID- 3340395 TI - Carcinogenicity of flour infested with Tribolium castaneum using the Egyptian toad Bufo regularis as a biological test animal. AB - Feeding the Egyptian toad Bufo regularis for 14 weeks with flour infested for 1 year with Tribolium castaneum, at a dose level of 200 mg/50 g body weight, induced neoplasms in 22 out of 100 toads. These neoplasms comprise 22 primary hepatocellular carcinomas and 6 tumours in the kidney due to metastases from the primary hepatocellular carcinoma. It is speculated that the carcinogenicity of the flour used in this work is due to quinone derivatives secreted by the defensive glands of T. castaneum. PMID- 3340396 TI - Low-grade non-Hodgkin's lymphoma in Zimbabwe: clinical features and stage. AB - Fifteen patients with low-grade non-Hodgkin's lymphoma were seen in Harare over a 3-year period, and this group constituted approximately 17% of all non-Hodgkin's lymphoma. All but one were of type A (Working Formulation), i.e. small lymphocytic. This low proportion of lesser grades of malignancy and virtual absence of follicular histology was similar to findings in other parts of Africa. The clinical features, however, resembled those reported worldwide with the sex ratio equal, older patients affected, and most patients (87%) having advanced stage disease, often with extranodal spread. PMID- 3340397 TI - Reliability of lens implant power formulas in hyperopes and myopes. AB - Calculations were made comparing a variety of formulas in patients who required unusually high and low power intraocular lenses. Of the formulas tested, the author found the Colenbrander formula to be more accurate for myopic patients and the SRK formula to be more accurate for hyperopic patients. PMID- 3340399 TI - Tarsorrhaphy for corneal disease in patients with rheumatoid arthritis. AB - We report two patients with keratoconjunctivitis sicca and rheumatoid arthritis whose corneal surfaces regained their integrity following tarsorrhaphy when conservative therapeutic measures were unsuccessful. We suggest that tarsorrhaphy be considered early in the course of the disease in such patients when other measures have failed to arrest progressive thinning of the cornea. PMID- 3340398 TI - In vitro inhibition of lens epithelial cell proliferation and migration. AB - Delayed opacification of the posterior capsule is the most common cause of decreased visual acuity after extracapsular cataract extraction. In humans, this has been shown to result from migration and possibly proliferation of residual lens epithelial cells onto the central posterior capsule. We studied a group of pharmacologic agents to determine their ability to inhibit lens epithelial cell proliferation and migration in vitro. A drug capable of inhibiting lens epithelial cell growth and/or migration, if free of unacceptable toxic effects on other cell populations, might be used to prevent lens capsule opacification. Anti proliferative activity was exhibited by several agents, with 50% inhibition of growth occurring at the following concentrations: 5-fluorouracil, 30 micrograms/ml; daunomycin, 10 ng/ml; colchicine, 15 ng/ml; doxorubicin, 5 ng/ml; dexamethasone, 100 micrograms/ml; and cytosine arabinoside, 100 ng/ml. Colchicine inhibited lens epithelial cell migration by 50% at 20 ng/ml. PMID- 3340400 TI - Double stent intubations in difficult post-traumatic dacryocystorhinostomy. AB - Nasolacrimal obstruction following mid-facial trauma can be a difficult challenge for the lacrimal surgeon. After the initial bony repair with wires, or screws and plates, the reconstruction of the lacrimal drainage pathway can be accomplished best after at least 3 months. We describe methods of sac stent and canalicular intubation that can be used as a double stent intubation technique for severely traumatized patients. PMID- 3340401 TI - Surgical removal of an "inoperable" neurofibroma. AB - An 8-month-old girl had ipsilateral ptosis, proptosis, and glaucoma caused by a massive left-sided plexiform neurofibroma. The tumor extended from the cavernous sinus into the orbit, involving the optic nerve, extraocular muscles, and eyelid. Although the prognosis in such cases is considered very poor, most of the mass was excised by a radical neurosurgical and ophthalmologic procedure. Today, the patient remains asymptomatic with no further neurologic defects. This case is unusual in that the glaucoma developed prior to clinically evident eyelid involvement. PMID- 3340402 TI - Community eye care 10 years after Alma Ata: progress, problems, and priorities for private voluntary organizations in developing nations. AB - The 1978 International Conference on Primary Health Care held in Alma Ata, USSR, made a strong appeal for recognizing that blindness is avoidable. Most blindness can be cured by medical and surgical means, or prevented by public health measures. Now, 10 years later, it is appropriate to review and evaluate a decade of primary eye care. This article describes and reviews from a managerial perspective at three levels of intervention a community eye care program for Afghan refugees established in 1982 by the League of Red Cross in Pakistan. Factors for success and problems are analyzed, and priorities for the future are suggested. PMID- 3340404 TI - Technique for slit lamp comparison of anterior chamber depth. AB - A quick, clinically useful, and easily performed technique is described that permits comparison of anterior chamber depths of both eyes in the same patient. PMID- 3340403 TI - The use of video to monitor continuous gold laser photoradiation treatment of an ocular melanoma. AB - A video system to monitor continuous Gold laser photoradiation treatment of an ocular melanoma is described. We believe this technique considerably improves the safety and accuracy of continuous laser treatment. PMID- 3340405 TI - A versatile pneumatic module for intraocular microsurgery. PMID- 3340406 TI - An inexpensive fiberoptic light pipe to aid in placement of episcleral radioactive plaques. AB - Episcleral plaque placement requires accurate localization of choroidal melanomas. Available fiberoptic light pipes can be fashioned to become scleral markers and transilluminators. The equipment is available wherever posterior segment surgery is performed. Surgical technique and equipment modifications are described. PMID- 3340407 TI - A new sling material for ptosis patients. AB - Patients with poor or total absence of levator function require correction of their ptosis by a sling procedure. The aim of the procedure is to utilize the action of the frontalis muscle, innervated by the seventh nerve, to mechanically raise the droopy eyelid. The most common materials used for the sling are autogenous or preserved fascia lata and synthetic products such as nylon or dacron sutures. We introduce a new material for the sling procedure--preserved placental umbilical vein modified for the use as a sling. Two cases are presented in which this material was used with excellent results. PMID- 3340408 TI - Glass Houses? PMID- 3340409 TI - Orbital surgery for head and neck surgeons. PMID- 3340410 TI - The Medical Practice Act of 1985. Part IX--Implementing the regulations for non physician health care professionals. PMID- 3340411 TI - Strategies for fees. PMID- 3340412 TI - Neonatal Campylobacter meningitis. PMID- 3340414 TI - Nurses are unsung heroes of medical care. PMID- 3340413 TI - Infection protection in hospitals. PMID- 3340415 TI - Social phobia: the shyness that is an illness. PMID- 3340416 TI - Major medical insurance: a fact of life. PMID- 3340417 TI - Chronic musculoskeletal pain and functional status in juvenile rheumatoid arthritis: an empirical model. AB - An empirical model is proposed and tested on variables hypothesized to influence functional status in 23 children with juvenile rheumatoid arthritis experiencing chronic musculoskeletal pain. Child psychological adjustment, family psychosocial environment, chronic musculoskeletal pain, and disease activity were entered into multiple regression analyses to statistically predict 4 functional status criterion variables: activities of daily living (ADL), activities involvement, school functioning, and social functioning. Predictor variable relationships were found for all 4 functional status criterion variables, suggesting initial support for this empirical model of functional status in children with juvenile rheumatoid arthritis experiencing chronic musculoskeletal pain. PMID- 3340418 TI - Spontaneous and evoked release of met-enkephalin-like material from the spinal cord of arthritic rats in vivo. AB - Perfusion of the intrathecal space with artificial CSF was achieved in control and arthritic rats under halothane anaesthesia in order to collect the met enkephalin-like material (MELM) released from the whole spinal cord. On the fourth week following the intradermal injection of Freund's adjuvant to induce arthritis, a marked reduction (-56%) in the spontaneous outflow of MELM was noted in arthritic rats. This effect did not involve changes in the degradation process of MELM, since it persisted when kelatorphan was added to the perfusing fluid in order to inhibit completely the peptidases acting on met-enkephalin. Raising the K+ concentration in the perfusing fluid from 2.4 to 40 mM, as well as moving the hind paws, produced a significant enhancement of MELM release which was (at least) as pronounced in arthritic as in control rats. These results suggest that the basal activity of spinal enkephalinergic neurones, but not that triggered by various stimuli, is reduced in arthritic rats. PMID- 3340419 TI - Stimulation of the nucleus paraventricularis thalami suppresses scratching and biting behaviour of arthritic rats and exerts a powerful effect on tests for acute pain. AB - In 20 arthritis-sensitive Wistar rats, an electrode was implanted in the paraventricular thalamic nucleus (PV). In the tail-flick and hot-plate test, PV was stimulated continuously for a period of 30 min, during which every 5 min either a tail-flick or hot-plate test was performed. Stimulation of PV induced important prolongations of the reaction times on tail-flick and hot-plate tests. However, there was no significant correlation between the results of the two tests. The effect of stimulation was immediate and did not outlast the stimulation period. PV stimulation did not give rise to tolerance, either within the stimulation period of 30 min, or during the successive testing days. After the termination of these acute pain tests, rats were inoculated with Mycobacterium butyricum. All animals developed polyarthritis. PV stimulation had a profound suppressive effect on the scratching and biting behaviour displayed by the animals. This reduction in scratching and biting behaviour was specific for PV stimulation since stimulation of another target, the ventrolateral thalamic nucleus (4 animals), had no effect on these behaviours. The attenuation of the scratching and biting behaviour was not a result of a general motor impairment, since other behaviours increased (running and sniffing) or did not change. There was no significant correlation between the results of scratching behaviour with those of the tail-flick and hot-plate test. PMID- 3340420 TI - The effects of myofascial trigger point injections are naloxone reversible. AB - Ten patients with myofascial trigger point pain were entered into a double-blind cross-over study of the reversibility of myofascial trigger point injection (TPI) effects with naloxone versus placebo in order to test the hypothesis that the benefits of TPI are mediated, at least in part, through activation of an endogenous opioid system. Injection of trigger points with 0.25% bupivacaine decreased pain in all subjects and increased range of motion in subjects who, on initial assessment, demonstrated limitations of movement of the affected part(s). Allodynia and palpable bands preceding TPI when present also showed reduction after TPI. All improvements afforded by TPI were significantly reversed with intravenous naloxone (10 mg) compared to intravenous placebo. These results demonstrate a naloxone-reversible mechanism in TPI therapy. This suggests an endogenous opioid system as a mediator for the decreased pain and improved physical findings following injection of myofascial trigger points with local anesthetic. PMID- 3340421 TI - Pain measurement in reflex sympathetic dystrophy syndrome. AB - The reflex sympathetic dystrophy syndrome (RSDS) consists of a triad of pain, edema and sympathetic dysfunction of an extremity following trauma, peripheral nerve injury or central nervous system disorder. Reflex sympathetic dystrophy syndrome is a difficult and costly pain syndrome to treat. One of the difficulties in evaluating treatment efficacy is the objectification and quantification of patient findings. The purpose of this investigation was to develop a simple, reproducible and systematic evaluation of pain and neurologic impairment in RSDS. The protocol evaluation included the following measures of pain and impairment: (1) objectification of distal joint pain by palpation (0-4 scale); (2) volumetric measurement by water displacement of the distal limb; (3) skin temperature measurement; (4) active range of motion assessment of the affected limb (AROM); (5) McGill Pain Questionnaire (MPQ); and (6) visual analogue pain scale (VAS). Seventeen subjects with definite or probable RSDS were evaluated. The mean age of patients was 35.6 years +/- 8.0 years (+/- 2 S.E.M.), and the mean duration of symptoms was 11.8 +/- 4.8 months. There were an equal number of subjects with upper and lower extremity involvement. The VAS had significant correlations with limb volume, AROM-lower extremity and joint pain indices (P less than 0.0005). The MPQ subscales had robust correlation with the joint pain indices alone (P less than 0.0001). Skin temperature was not predictive of changes in joint pain score, AROM, limb volume or subjective pain measures. However, there was internal consistency between volumetric and AROM measures and joint pain indices. This protocol is recommended for use in therapeutic trials for the treatment of the RSDS. PMID- 3340422 TI - A multiple random staircase method of psychophysical pain assessment. AB - Three experiments evaluated the reliability and sensitivity of an interactive multiple random staircase (MRS) assessment of painful thermocutaneous sensations. One hundred and sixteen subjects used a 4-point category scale (no pain, mild, moderate, intense) to rate the intensity of sensations produced by 3-sec thermal stimuli applied to the volar forearm at 20-sec intervals by a 1-cm diameter contact thermode. Each of the 3 intervals between the 4 verbal responses was defined as a boundary. A pair of staircases was associated with each boundary. On each trial, 1 of the 6 staircases was chosen randomly and the stimulus intensity indicated by that staircase presented. The response to that stimulus determined the intensity presented by that staircase the next time it was randomly selected. Responses above the associated boundary decreased stimulus intensity, responses below the associated boundary increased stimulus intensity. In the first experiment, 1 staircase from each of the 3 boundaries began at 43 degrees C and 1 began at 48 degrees C. Staircases for each boundary converged to within 0.3 degree C after 12 trials/staircase. The sensitivity of the method to a narcotic analgesic was assessed by open (exp. II) and double-blind (exp. III) intravenous infusion of 1.1 micrograms/kg fentanyl. Administration of fentanyl increased staircase temperatures, indicating that these higher temperatures were now required to elicit the same verbal responses. This shift in temperature reached a peak effect 11 min after fentanyl administration. These results suggest that this method provides a reliable measure of sensory magnitude in units of stimulus intensity. It does not require assumptions about psychological units of pain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3340423 TI - Family dynamics and emotional expression among patients with chronic pain and depression. AB - Exploration of the relative roles of family dynamics and release of constrained, negative emotion in changing pain and depressive symptoms. Eighteen patients presenting mild to moderate depression and diagnoses of psychogenic pain disorder were randomly assigned to 1 of 2 treatment groups. One group was designed to facilitate the release of constrained and overcontrolled negative affect while the other was designed to provide information about pain and depression. Findings suggest that initial incongruity between patient's and significant other's ratings of family relationships retard changes in pain status and depressive symptoms. No significant differences were noted between patients who were taught to express negative feelings and those who were taught simply to understand those feelings. Results are discussed in terms of theories about family dynamics in the initiation and maintenance of pain conditions and in terms of the role of constrained affect as a precursor to both psychogenic pain and depression. PMID- 3340424 TI - Pelvic pain: an undescribed paroxysmal manifestation of multiple sclerosis. AB - We report a patient with pelvic pain as a paroxysmal manifestation of multiple sclerosis (MS). This phenomenon has not been described previously; it can lead to diagnostic difficulties. Like other paroxysmal manifestations, it showed a good response to carbamazepine. The literature on paroxysmal manifestations of MS and some possible pathogenic mechanisms are reviewed briefly. PMID- 3340425 TI - A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. AB - A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold. PMID- 3340426 TI - Myelinated afferents signal the hyperalgesia associated with nerve injury. AB - Pain to light touching of the skin is a hallmark sign of causalgia. The purpose of this study was to determine whether myelinated or unmyelinated afferent fibers signal this hyperalgesia. Sensory testing was performed in 17 patients with long standing hyperalgesia after nerve injury. The patients underwent a differential ischemic block of nerve function of the involved area. At a time when touch sensation in adjacent normal skin was eliminated, but when sensibility to warming and cooling stimuli was unaffected, the hyperalgesia to mechanical stimuli was abolished in 15 of the subjects. In 2 of these 15 patients, a differential local anesthetic block of the injured nerve was performed proximal to the site of injury. When temperature sensibility was absent, but when touch sensation was intact, hyperalgesia was present. In a third study, latency measurements in response to 400 micron stepped displacement stimuli were made in two patients who had hyperalgesia on the foot. The mean latency for detection of pain in the hyperalgesic region was 414 +/- 18 msec, compared to 458 +/- 16 msec for the detection of touch to the same stimuli applied to the opposite normal foot. These 3 lines of evidence indicate that myelinated primary afferents, perhaps A beta fibers, signal the hyperalgesic pain in causalgia. These fibers may be sensitized A beta nociceptors or low-threshold mechanoreceptors. PMID- 3340428 TI - Current views on posterior urethral valves. PMID- 3340427 TI - Low dose epidural morphine does not affect non-nociceptive spinal reflexes in patients with postoperative pain. AB - In order to determine the selectivity of the antinociceptive effect of epidural morphine, the electrophysiological features of a monosynaptic reflex were investigated before and after epidural morphine (2-3 mg) required for pain relief, in 4 patients suffering from postoperative pain. The reflex tested was the H reflex from the soleus muscle. Not only the classical Hmax/Mmax ratio, but also the threshold and the slope of the rising phase of the recruitment curve of H and M responses were analyzed. It was found that epidural morphine did not change significantly any of these parameters, at least during the 60 min post injection period. By contrast, as usually observed clinically, epidural morphine produced an onset of pain relief by the 25th-30th min following injection. These data support the hypothesis that epidural morphine produced a 'selective spinal analgesia in man.' PMID- 3340429 TI - Pediatric gastroenterology. PMID- 3340430 TI - Use of the barium enema in the diagnosis of necrotizing enterocolitis. AB - Necrotizing enterocolitis (NEC) is associated with considerable morbidity and mortality in infants. The diagnosis relies heavily upon radiographic and clinical features. Failure to accurately diagnose NEC is associated with a risk of complications and death, however overdiagnosis also causes both morbidity and mortality as well as excessive medical costs. This report documents the use of barium enema to evaluate suspected clinical or radiographic NEC in 31 premature infants with ambiguous clinical and radiographic signs. The enema was normal in 26 infants and no treatment for NEC was given. Only one of these infants developed signs of NEC subsequent to the examination. Five infants had radiographic evidence of colitis including small ulcerations, spasm, intramural extravasation of barium and mucosal irregularity. Two of the five positive cases are pathologically documented. The barium enema can represent a significant improvement in the specificity of the diagnosis of NEC. Its greatest value is in the exclusion of NEC in ambiguous cases. PMID- 3340431 TI - Pneumatic reduction of ileocolic intussusception in children. AB - Pneumatic reduction of ileocolic intussusception in children has been used in Argentina and in China for more than 25 years but has only recently been attempted in North America. It is reported to be safer and more effective than reduction by the hydrostatic pressure of a barium suspension. Our preliminary experience with four patients has been rewarding and we believe it may become the method of choice. PMID- 3340432 TI - Hepatobiliary scintigraphy in arteriohepatic dysplasia (Alagille's syndrome). A report of two cases. AB - Hepatobiliary scintigraphy has proven to be of great utility in distinguishing biliary atresia from other causes of neonatal cholestasis. Arteriohepatic dysplasia (Alagille's syndrome) is an uncommon entity characterized by typical facial features, pulmonary artery stenosis, and a liver disorder which presents during the neonatal period as progressive jaundice. Two neonates, who were later shown to have Alagille's syndrome, underwent hepatobiliary scintigraphy to rule out biliary atresia. Findings on the hepatobiliary scans from the two patients were similar to those usually associated with biliary atresia and both finally required surgical exploration to rule out biliary atresia. The findings on hepatobiliary scans in these patients with Alagille's syndrome are discussed and compared with those associated with other forms of neonatal cholestasis. PMID- 3340433 TI - The scintigraphic and radiographic appearance of the ischiopubic synchondroses in normal children and in osteomyelitis. AB - Five cases of hematogenous osteomyelitis of the ischiopubic synchondrosis (IPS) were encountered among 180 patients with osteomyelitis treated over a 5-year period. Symptoms were poorly localized in all these IPS osteomyelitis patients. The IPS can normally show expansion and irregular mineralization radiographically and focal hyperconcentration of radiophosphates on scintigrams. Findings are frequently asymmetrical negating comparison with the contralateral side. In the cases of osteomyelitis, radiographs were abnormal at the time of presentation in only one of these five cases. In two of the four patients who had radionuclide bone scans, activity at the IPS exceeded that seen in a normal control population, but all showed loss of definition of the IPS and regional increased uptake permitting an early diagnosis. PMID- 3340435 TI - Acro-mesomelic dysplasia--a new type. Report of two siblings. AB - Two siblings who represent a new type of acro-mesomelic dysplasia are reported. The unique pattern of the acro-mesomelic hypoplastic/dysplastic changes allows us to designate them as a new syndrome. PMID- 3340434 TI - Radiological features in congenital erythropoietic porphyria (Gunther's disease). Report of 3 cases. AB - Gunther's disease or congenital erythropoietic porphyria is a rare and severe disorder comprising cutaneous and haemolytic symptoms. Photocutaneous lesions are responsible for scleroderma-like calcifications and deformities of the extremities visible on X-rays. Hemolytic manifestations lead to diffuse major osteopenia. Soft tissue calcifications of the fingers can be seen even in young patients. One case reported here is the first illustration of intracranial calcifications located on dura-mater and calvarium. PMID- 3340436 TI - Scintigraphy of major closed chest cardiac trauma in childhood. PMID- 3340437 TI - Pulmonary emphysema in neonate with the Marfan syndrome. PMID- 3340439 TI - European Society for Paediatric Endocrinology. Abstracts for the 26th annual meeting, September 6-8, 1987, Toulose, France. PMID- 3340438 TI - Diaphragmatic and genioglossus electromyographic activity at the onset and at the end of obstructive apnea in children with obstructive sleep apnea syndrome. AB - We studied the activity of the diaphragm and of the genioglossus at the onset and at the end of obstructive sleep apnea in children. Seven children (mean age 46 months, range 15-87) with obstructive sleep apneas mainly due to enlarged tonsils were tested during natural sleep. We recorded sleep stages (neurophysiological criteria), nasal and buccal air flow (thermistors), thoracoabdominal motion (magnetometers), genioglossus and diaphragm electromyographic activity (EMG) (surface electrodes), and transcutaneous partial pressure of oxygen (Radiometer 44 degrees C). A total of 153 obstructive apneas for the whole group of patients was studied. Compared to the preceding unoccluded breaths, genioglossus and diaphragm EMG data showed that 1) at the onset of obstructive apnea there was no significant decrease in genioglossus and/or diaphragm EMG, contrasting with published data for obese adults, and 2) at the end of obstructive apnea, significant preferential increase in genioglossus EMG, not related to the decrease in transcutaneous partial pressure of oxygen, was found as in obese adults. This study showed that different mechanisms may control the onset of obstructive apnea in children as compared to adults, whereas children and obese adults share the same preferential increase in genioglossus EMG at the end of obstructive apnea. PMID- 3340440 TI - Effect of reconstituted pulmonary surfactant containing the 6000-dalton hydrophobic protein on lung compliance of prematurely delivered rabbit fetuses. AB - Chloroform:methanol extracts of bovine pulmonary surfactant contain small hydrophobic proteins, designated surfactant-associated apoproteins 6,000 (SAP-6), but do not contain the major surfactant-associated 35,000-dalton glycoprotein, designated SAP-35. Examination of lipid extract surfactant on sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed hydrophobic proteins with apparent molecular masses of 15,000, 7,000, and 3,5000 daltons prior to reduction. After reduction, the 15,000-dalton species largely disappeared and was replaced by a 5,000-dalton species. In addition, the 7000- and 3500-dalton species exhibited a slightly enhanced mobility. Amino acid analysis demonstrated that SAP-6 possesses a more highly hydrophobic profile than SAP-35. Combining the protein-containing fractions from silicic acid chromatography of lipid extract with synthetic dipalmitoylphosphatidylcholine produced a reconstituted surfactant preparation which was just as active as lipid extract surfactant on a pulsating bubble surfactometer. The reconstituted surfactant contained SAP-6 but not SAP 35. Pressure-volume studies revealed that, at the optimal dose, reconstituted surfactant containing half the SAP-6 concentration of lipid extract exhibited similar effectiveness to lipid extract surfactant in promoting lung expansion with prematurely delivered rabbit fetuses of 27 days gestation. Reconstituted surfactant with an identical SAP-6 protein concentration as lipid extract possessed the same biological properties as the preparation with 1% SAP-6 protein. These studies support the view that an artificial surfactant composed of synthetic or semisynthetic lipids plus human SAP-6 produced via biotechnology could be useful for prevention and/or treatment of the neonatal respiratory distress syndrome. PMID- 3340441 TI - Taurine and osmoregulation: taurine is a cerebral osmoprotective molecule in chronic hypernatremic dehydration. AB - We studied the effect of 8-wk dietary taurine depletion on the vulnerability to hypernatremic dehydration in postweanling kittens. While experimental taurine depletion was not associated with increased susceptibility to acute hypernatremia (1.5 M NaCl/NaHCO3, 35 ml/kg body weight, single injection), there was an increase in mortality (five of seven versus one of seven, p = 0.05) and seizure activity (three of seven versus none of seven, p = 0.08) in taurine-depleted compared to taurine-replete kittens rendered chronically hypernatremic over 96 h. Furthermore, there was a significant decrease in brain cell water (517.4 +/- 21.7 versus 671.6 +/- 32.3 ml/100 g fat-free dry weight, p less than 0.05), derived almost exclusively from the intracellular compartment (352.5 +/- 12.3 versus 483.8 +/- 34.6 ml/100 g fat-free dry weight, p less than 0.05) that correlated with the reduction in the cerebral taurine content in the taurine-depleted versus control kittens during chronic hypernatremic dehydration. These results suggest that taurine is an important cerebral osmoprotective molecule. This aminoacid constitutes nearly 50% of the adaptable intracellular osmolal pool whose concentration varies in the course of osmoregulating in response to perturbations in the extracellular fluid tonicity. PMID- 3340442 TI - Transamination and oxidative decarboxylation rates of branched-chain 2-oxo acids in cultured human skin fibroblasts. AB - Transamination and oxidative decarboxylation of branched-chain L-amino acid derived 2-oxo acids in cultured human skin fibroblasts from normal subjects and from a patient with maple syrup urine disease (variant form) were comparatively studied in incubations with 1-14C-labeled substrates (1 mmol/liter). With normal cells, 14CO2 release ranged from about 11 to 3 nmol/90 min/mg of cell protein in the order 3-methyl-2-oxo[14C]butanoate greater than (S)-3-methyl-2 oxo[14C]pentanoate greater than 4-methyl-2-oxo[14C]pentanoate greater than (R)-3 methyl-2-oxo[14C]pentanoate. Formation of the corresponding branched-chain amino[14C] acids was substantially higher than 14CO2 production (around 10-fold) and similar with L-valine, L-isoleucine, and L-leucine. L-Allo-isoleucine production [from (R)-3-methyl-2-oxopentanoate] was significantly lower. With maple syrup urine disease fibroblasts, comparable transamination rates were observed. Related to the findings with normal cells, 14CO2 release from each substrate was differently reduced and apparent residual branched-chain 2-oxo acid dehydrogenase complex activity with 3-methyl-2-oxobutanoate, 4-methyl-2 oxopentanoate, (S)-, and (R)-3-methyl-2-oxopentanoate amounted to 12, 13, 22, and 50%, respectively. PMID- 3340443 TI - Uterine metabolism of the pregnant guinea pig as a function of gestational age. AB - During the last half of pregnancy, the fetal guinea pig grows exponentially at 7.1%/day. In order to define the metabolic requirements of the gravid uterus during this period of rapid growth, catheters were placed in the femoral artery and uterine vein of guinea pigs at gestational ages ranging from 40 days to term (68 days). The animals were studied in the unstressed state after full recovery from surgery and anesthesia. Arterial and venous concentrations of oxygen, glucose, lactate, acetoacetate, beta-hydroxybutyrate, and acetate were measured, and metabolic quotients and coefficients of extraction were calculated. The glucose/oxygen quotient did not change significantly in the last half of pregnancy averaging 1.26, while the lactate/oxygen quotient remained unchanged at -0.42, and the (glucose + lactate)/oxygen quotient remained unchanged at 0.82. Coefficients of extraction of glucose and oxygen increased linearly with gestational age. The increase in supply of substrates for the rapid growth of the conceptus toward the end of gestation is accounted for by increasing extraction of substrate and by greatly increasing blood flow with increasing gestation. While glucose remains the major metabolic fuel of the guinea pig conceptus and acetate is consistently taken up by the uterus, these substrates alone cannot account for the metabolic fate of the oxygen taken up and fall far short of the predicted nutritional requirements of the fetus for both oxidative metabolism and growth. PMID- 3340444 TI - Retinal oxygen tension is higher in light than dark. AB - The oxygen tension at the inner retinal surface in rabbits was measured with intraocular polarographic electrodes. In the air breathing rabbit, the oxygen tension is 21 +/- 9 mm Hg (mean +/- 1 SD, n = 6) in 12 foot-candles white light at the cornea. The oxygen tension falls 6 +/- 2 mm Hg (mean +/- 1 SD, n = 4, p less than 0.02) in darkness. In bright white light (800 foot-candles), the retinal oxygen tension is about 6 mm Hg higher than at 12 foot-candles. The in vivo retinal oxygen consumption was calculated to be 2.4 ml O2/100 g/min in light and 2.6 ml O2/100 g/min in dark. The higher oxygen consumption is probably responsible for the lower oxygen tension of the retina in dark as compared to light. Breathing 100% oxygen elevates the preretinal oxygen tension to 190 +/- 72 mm Hg (mean +/- 1 SD, n = 4) in light. PMID- 3340445 TI - Lack of inhibition of intestinal heme oxygenase by antibiotics and tin protoporphyrin. AB - We assessed the in vivo and in vitro effects of antibiotics and tin protoporphyrin (TP) on intestinal heme oxygenase (HO) activity using a gas chromatographic assay. This method measures the carbon monoxide produced from heme in the presence of NADPH. After in vivo administration of kanamycin (10 mg/kg body weight), ampicillin (200 mg/kg body weight) or neomycin (60 mg/kg body weight) with or without TP (65 mumol/kg body weight) to suckling rats, no significant difference in HO activity along the small intestine was observed. In vitro exposure of adult rat intestinal preparations to the antibiotics showed no significant decrease in HO activity between control and experimental tissue preparations. A concentration-dependent stimulatory effect of neomycin was observed. Subcutaneous administration of TP (25 mumol/kg body weight) to adult male Wistar rats revealed no significant inhibition of the intestine. However, in vitro addition of TP (12.5 microM) to the control tissue preparations of adult Wistar rats revealed highly significant inhibition in liver and spleen when compared to the unexposed control tissues. In contrast, when TP was added to control intestinal preparations no inhibition was observed. These findings suggest that suckling rat intestinal heme oxygenase is not inhibited by in vivo treatment with high concentrations of kanamycin, ampicillin, or neomycin. Furthermore, these antibiotics are not in vitro inhibitors of adult rat intestinal HO. Finally, adult rat intestinal HO is not inhibited either in vivo or in vitro by a concentration of TP that significantly inhibits liver and spleen activity. PMID- 3340446 TI - Effect of hypercapnia and hypoxia on costal and crural diaphragm electromyograms in piglets. AB - We examined the separate effects of acute hypercapnia and acute hypoxia, on the electromyographic activity (EMG) of the costal and crural diaphragm in 6 anesthetized spontaneously breathing piglets (age 12-23 days, weight 3.00-4.37 kg). Bipolar wire electrodes were inserted into the anterior paratendinous costal diaphragm and the midportion of the crural diaphragm. EMG activity was quantified in arbitrary units (au) of peak moving time average while the animals breathed 50% O2/50% N2 (base-line) and after 30 min of either hypercapnia (12% CO2) or hypoxia (12% O2) exposure. After 30 min of hypercapnia, the peak moving time average EMG increased in both parts of the diaphragm with the increase in crural diaphragm EMG activity (from baseline: 20 +/- 2 au to 30 min 12% CO2: 83 +/- 20 au) not being significantly different from that observed in the costal diaphragm (from baseline: 21 +/- 2 au to 30 min 12% CO2: 72 +/- 20 au, p = 0.17). Similarly, the peak moving time average EMG increased in both parts of the diaphragm after 30 min of hypoxia with the increase in the crural diaphragm EMG activity (from baseline: 21 +/- 2 au to 30 min 12% O2: 28 +/- 6 au) not being significantly different from that observed in the costal diaphragm (from baseline: 21 +/- 1 au to 30 min 12% O2: 26 +/- 7 au, p = 0.51). These data indicate that the inspiratory EMG activity of the diaphragm is not differentially distributed between its costal and crural components during chemically stimulated breathing in piglets. PMID- 3340448 TI - Hyperphenylalaninemia in the hph-1 mouse mutant. AB - A mutation, resulting in a deficiency of liver GTP-cyclohydrolase activity, has been induced in the laboratory mouse. Mice homozygous for this mutation exhibit hyperphenylalaninemia under the following conditions: 1) early in life and 2) throughout life when exposed to phenylalanine. A phenylalanine loading regimen was used to discriminate between mutant and wild type mice on the basis of the resultant phenylalanine and tyrosine serum levels. Subjecting mice to this regimen reveals several distinguishing characteristics. Mutant mice exhibit approximately 2-fold higher peak phenylalanine levels than wild-type mice. In wild-type mice the hyperphenylalaninemic state is transient and rapidly abates while in mutant mice it is persistent and remains for a prolonged period. Mutant mice exhibit normal serum tyrosine levels after a loading challenge, while wild type mice experience an increase in tyrosine levels. The loading regimen was also used to gauge the response of mutant hyperphenylalaninemic mice to exposure to chemical compounds required for normal phenylalanine catabolism (i.e. pteridine cofactors of the phenylalanine hydroxylase reaction). Mutant mice exposed to native enzyme cofactor or cofactor precursors exhibit a sharp decline in serum phenylalanine levels relative to their uninjected counterparts coupled with a tyrosine increase. By contrast, mutant mice exposed to nonprecursor compounds that are structurally related to the native cofactor, experience no diminution of serum phenylalanine levels. PMID- 3340447 TI - The distribution of lead in milk and the fate of milk lead in the gastrointestinal tract of suckling rats. AB - Milk can be a significant source of lead (Pb) for young mammals, including humans. Certain essential trace elements have previously been shown to be specifically associated with particular milk components and such associations often increase bioavailability. Thus, the first goal of this study was to determine the distribution of Pb in cream, casein, and whey fractions of various milks under various conditions using 203Pb as a tracer. In rat milk almost 90% of the Pb was found to be associated with the casein micelles, regardless of: 1) whether the milk was labeled in vivo or in vitro; b) whether the milk was fresh or frozen; and c) the added concentration of Pb (over the range 0.01-75 micrograms/ml). The remainder of the Pb was approximately equally distributed between cream and whey. A virtually identical pattern of Pb distribution was observed with bovine milk. Pb added to infant formula also associated predominantly with casein micelles, although the Pb content of this fraction was significantly less than with rat and bovine milks. The second goal of the study was to determine if Pb remained associated with casein as it traversed the gastrointestinal tract of infant rats. For this purpose, rat pups aged 15-16 days were gavaged with 203Pb-labeled rat milk, and lumenal contents from the stomach and small intestine were collected 2 h later. Differential centrifugation of the homogenized lumenal contents showed that in the stomach the Pb was associated primarily with the casein curd. By the time chyme reached the distal small intestine, Pb was found predominantly in a fraction that was not precipitable by high-speed centrifugation (thus, not intact casein micelles), but was nondialyzable. We conclude that Pb in milk is protein bound and remains this way as it traverses the stomach and proximal small intestine of the infant rat. PMID- 3340449 TI - Changes in ventilation homogeneity from preschool through young adulthood as determined by moment analysis of nitrogen washout. AB - This study was designed to assess potential differences in ventilation homogeneity related to growth. One hundred thirty-three healthy subjects representing four stages of growth were studied: group 1, preschool, ages 34-74 months; group 2, preadolescent, ages 8-10 yr; group 3, postpubertal, ages 15-17 yr; group 4, young adult, ages 26-40 yr. Ventilation homogeneity was assessed by moment analysis of multibreath nitrogen washout with functional residual capacity, the ratio of the 1st to 0th moment (MR 1/0), and the ratio of the 2nd to 0th moment (MR 2/0) being the outcome variables of interest. Across the four groups functional residual capacity increased as a curvilinear function of height. At all heights functional residual capacity was larger in males than females and the slope of the regression was steeper in males than females (p less than 0.001). Both MRs 1/0 and 2/0 were significantly higher in group 1 than the other groups, indicating that ventilation washout was less homogeneous in the preschool subjects than in older children or adults. Males of group 1 had significantly higher values for both moment ratios (more ventilation nonuniformity) than females. In the other groups there were no significant sex based differences although there was a trend for males to have a lower MR 1/0 than females in the young adults, p = 0.08. The results indicate that both age and sex are important determinants of the growth of distribution of ventilation. PMID- 3340451 TI - Control of water balance in infants with bronchopulmonary dysplasia: role of endogenous vasopressin. AB - Babies with chronic bronchopulmonary dysplasia (BPD) can sometimes develop pallor, systemic and pulmonary edema, oliguria, and hyponatremia not attributable to cardiopulmonary or renal impairment. These signs and symptoms might, however, be explained by inappropriate control of vasopressin secretion. To test this hypothesis, we measured plasma vasopressin and osmolality, serum sodium and potassium concentrations, urine output and osmolality, and free water clearance in 26 normoxic infants with BPD aged 1-4 months. All of these infants required supplemental oxygen (FiO2 0.41 +/- 0.03, mean +/- 1 SE) to maintain O2 saturation of greater than 88%, and six infants also required mechanical ventilation. As controls, 10 infants of similar age but without BPD were also studied. None of the infants had been discharged from the nursery and was receiving any medications, and all were clinically stable when studied. Compared to control infants, infants with BPD had significantly elevated plasma vasopressin concentrations (control 5.2 +/- 0.9 pg/ml; BPD 42.4 +/- 5.1; mean +/- SE, p less than 0.05). Moreover, infants with BPD had hyponatremia and hypotonic plasma, and both urine output and free water clearance were significantly reduced. These data suggest that some infants with chronic BPD have elevated vasopressin levels that are functionally significant. We speculate that excessive stimulation of vasopressin secretion may explain some of the pulmonary and nonpulmonary signs and symptoms in infants with chronic BPD. PMID- 3340450 TI - Vitamin A deficiency and pulmonary oxygen toxicity: morphometric studies in the murine lung. AB - Vitamin A and its precursor beta-carotene are naturally occurring antioxidants. The effects of diets deficient in beta-carotene and vitamin A on the alveolar capillary membrane were studied in young adult BALB/C mice before and after exposure to 65% oxygen. One of three diets (standard complete, beta-carotene deficient, or beta-carotene and vitamin A deficient) was fed for a 6-wk period. Mice were then exposed to 65% oxygen for 0, 3, or 6 days, sacrificed, and their lungs examined by electron microscopy using the morphometric techniques of Weibel. The arithmetic and the harmonic mean thicknesses of the alveolar capillary membrane and its components (epithelium, interstitium, and endothelium) were measured to assess the influences of diet and of duration of exposure to 65% oxygen. Analysis of variance and multiple comparisons of means (Student-Neuman Keuls statistics) were applied. Diet alone did not significantly affect membrane thickness. However, duration of oxygen exposure increased the thicknesses of both the epithelium and interstitium in the group fed a diet deficient in both beta carotene and vitamin A as compared to the other two groups although this was only significant for the epithelium. beta-Carotene deficiency alone did not affect the respiratory membrane either before or after oxygen exposure. These results suggest that vitamin A may be an important nutrient in the protection against pulmonary oxygen toxicity. PMID- 3340452 TI - Quantitation of urinary growth hormone in children with normal and abnormal growth. AB - Urinary growth hormone (GH) excretion was quantitated in 12-h overnight urine collections obtained from 31 control children, ages 3 to 17 yr (group 1); 21 children, ages 5 to 19 yr with GH deficiency (group 2), and 30 subjects, ages 10 to 18 yr with idiopathic growth failure and normal GH stimulation tests (group 3). The output of urinary GH was measured in one acromegalic woman. The authenticity of urinary GH, 22 kDa, was confirmed by high-performance liquid chromatography. The elution pattern of urinary GH was identical to that of biosynthetic and pituitary-derived GH. The immunoreactive profiles characterized by monoclonal immunoradiometric GH assay and standard GH radioimmunoassay were identical. The quantity of GH (mean +/- SEM per kg body weight) in group 1 (0.27 +/- 0.02 ng/kg) was significantly greater than group 2 (0.08 +/- 0.02 ng/kg) or group 3 (0.17 +/- 0.02 ng/kg, p less than 0.01). Approximately 50% of the subjects in group 3 had urinary GH measurements indistinguishable from those observed in the GH-deficient population. Twelve hypopituitary patients (group 2) excreted significantly greater amounts of urinary GH in the first 12 h after GH administration compared to the baseline period (0.41 +/- 0.07 versus 0.12 +/- 0.02 ng/kg, p less than 0.01). Markedly elevated output of urinary GH (2.0 ng/kg) was documented in one acromegalic patient. The data suggest that measurements of urinary GH may be a useful, simple, and noninvasive screening test for identifying patients with GH deficiency or excess. PMID- 3340453 TI - Effects of aspirin-like drugs on mitogen-stimulated DNA synthesis of lymphocytes from pregnant rats and offspring. AB - Previous studies have shown that salicylates and protein-calorie malnutrition compromise immunological responses in humans and experimental animals. The present study compared the effects of prenatal normal and low protein diets, with and without aspirin-like drug treatments, on lymphocyte blastogenesis measured by tritiated thymidine uptake for DNA synthesis in splenic lymphocytes from pregnant rats and their offspring following stimulation with the mitogens concanavalin A, phytohemagglutinin, and pokeweed mitogen. Aspirin treatment was associated with increased lymphocyte thymidine uptake for blastogenesis in pregnant rats fed the normal protein control diet and their offspring. The phytohemagglutinin stimulated increase detected in offspring lymphocytes could not be statistically guaranteed. A low protein diet alone and a normal protein diet combined with salicylamide treatment was associated with decreased blastogenesis in pregnant rats but not in their offspring. Salicylamide or aspirin combined with a low protein diet decreased blastogenesis in both dams and their offspring. Aspirin combined with a normal protein diet did not adversely affect blastogenesis in either pregnant rats or their offspring. This study suggests that low dietary protein and aspirin-like drugs may independently decrease lymphocyte blastogenesis of pregnant rats and in combination they may also reduce lymphocyte blastogenesis in offspring. The significance of increased lymphocyte blastogenesis in both mothers and offspring following aspirin treatment of pregnant rats fed a normal protein diet is unclear. PMID- 3340454 TI - Atrioventricular nodal function in the immature canine heart [corrected and republished article orginally printed in Pediatr Res 1987 Nov;22(5):616-20]. AB - Previous studies have suggested that the atrioventricular nodal functional refractory period in the neonate is equal to or shorter than that of the ventricle, providing little or no protection to the ventricle against rapid atrial rates and allowing closely coupled atrial beats to fall within the ventricular vulnerable period. We evaluated atrioventricular node function in 21 mongrel neonatal puppies, 3-15 days old, and 15 adult dogs utilizing intracardiac His bundle recording and stimulation techniques. The mean atrioventricular nodal functional refractory period (173.1 +/- 20.0 ms) exceeded both the ventricular effective refractory period (139.5 +/- 14.3) and ventricular functional refractory period (163.3 +/- 14.5) in the neonates. Furthermore, the atrioventricular node was the site of limiting antegrade conduction in all neonates. No ventricular arrhythmias were induced by atrial extrastimulation in any of the neonates. The site of conduction delay during atrial extrastimulation was confined to the atrioventricular node in 15/16 neonates (94%) while 1/16 (6%) had combined nodal and infranodal delay. The neonates developed Wenckebach, at significantly faster heart rates than the adults, but both groups developed Wenckebach at approximately twice the resting heart rate. Retrograde conduction was a consistent finding in the neonates. However, antegrade Wenckebach occurred at a significantly faster heart rate than retrograde Wenckebach suggesting different functional properties. Our data suggest that in the neonatal canine, the atrioventricular node functional refractory period is longer than both the ventricular effective refractory period and ventricular functional refractory period. Furthermore, the degree of protection offered by the neonatal atrioventricular node to the ventricle appears to be comparable to that of the adult. PMID- 3340455 TI - Misidentification of sexually transmitted organisms in children: medicolegal implications. PMID- 3340456 TI - Sepsis in febrile neutropenic children with cancer. AB - Infection is the leading cause of death in children with cancer. A retrospective review of 100 episodes of sepsis in 80 children with cancer for a 21-month period showed that 74% of isolates were Gram-positive bacteria. Coagulase-negative staphylococci were the most common pathogens, accounting for 35% of all isolates. Initial empiric antibiotic therapy of fever in neutrogenic cancer patients was piperacillin and tobramycin. All but 12% of the Gram-negative isolates were susceptible to one or both of the antibiotics. However, 31% of the Gram-positive isolates were resistant to both antibiotics and 38% of the coagulase-negative staphylococci were methicillin-resistant. All of the latter were susceptible to vancomycin. The increasing incidence of coagulase-negative staphylococci as causes of sepsis in cancer patients suggests that the choice of antibiotics for initial empiric therapy may need to include vancomycin or an antistaphylococcal penicillin depending on the local incidence of methicillin resistance. PMID- 3340457 TI - Imidazole therapy of coccidioidal meningitis in children. AB - The mortality related to coccidioidal meningitis (CM) has been reduced since the introduction of amphotericin B therapy, but children with CM continue to suffer significant morbidity. Some of this is related to the toxicity of the drug. We report nine children with CM treated with orally administered ketoconazole and intraventricularly administered miconazole. Four of them had been treated initially with amphotericin B with resultant failure in one and severe toxicity in all four. The other five children were treated only with imidazoles. All nine children had evidence of ventriculitis at the time of diagnosis and had ventriculoperitoneal shunts inserted for control of increased intracranial pressure. There was no relapse or recrudescence of CM in a follow-up period of 32 to 90 months on imidazole therapy. The coccidioidal complement-fixation antibody titers in the cerebrospinal fluid of the lateral ventricle became negative in all children 3 to 51 months after diagnosis (mean, 17 months). The serum antibody titers demonstrated a 16- to 256-fold decrease from their maximal levels. Four children are still receiving intraventricular miconazole whereas the others have not received miconazole for an average of 51 months. Therapy with the imidazoles was well-tolerated. The main morbidity was related to the shunts required for control of increased intracranial pressure. There was no evidence of hepatic toxicity and no clinical evidence of adrenal insufficiency although transient adrenal suppression was demonstrated at 4 but not at 24 hours after ketoconazole administration. PMID- 3340458 TI - Predictors for extraintestinal infection in Salmonella enteritis in Thailand. AB - To identify the risks and predictors for extraintestinal Salmonella infection (ETI) in infants and children with nontyphoidal Salmonella enteritis, we performed a retrospective review of 326 infants and children with diarrhea and rectal swab cultures positive for nontyphoidal Salmonella enteritis seen at Ramathibodi Hospital between 1981 and 1983. Nineteen patients had bacteremia. The overall rate of bacteremia was 5.8% which was 24.3% of those having blood cultures taken. Salmonella typhimurium was the most common cause of ETI and the most invasive among the common serotypes causing enteritis. The clinical characteristics of the patients with high probabilities of having ETI were: younger than 6 months of age; high body temperature; and immunocompromising conditions. The observed frequency of ETI in these patients was 21.9 to 26.3% compared with 0 to 0.7% in patients without those risk factors. PMID- 3340459 TI - Salmonella infections in infants in Hawaii. AB - In a 10-year cohort of 117 infants hospitalized in Honolulu with Salmonella infections, there were 12 infants with bacteremia or complications (simple bacteremia, 7; bacteremia with probably unrelated concurrent infection, 2; serious complications, 3). The rate of serious complications in this cohort was low and occurred only in infants with previous chronic illness or clinically obvious extraintestinal infection at the time of presentation. Antibiotics were not shown to be of benefit in reducing the frequency of complications; however, the sample size was too small to make definitive conclusions. These data do not support the contention that infants with Salmonella gastroenteritis are at increased risk of complications and should therefore be treated with antibiotics. Rather, the same clinical risk factors for sepsis that apply to all infants also apply to infants with Salmonella gastroenteritis and the decision to begin antibiotic treatment should be based on similar clinical information. PMID- 3340460 TI - Aeromonas-associated gastroenteritis in children. AB - During a 20-month period 55 strains of Aeromonas species were isolated from 53 children with diarrhea. The isolation rate of 2.5% for Aeromonas compared with the rates of 4.5% for Shigella, 3.3% for Salmonella, 2.7% for Campylobacter and 0.05% for Yersinia. In 45 children Aeromonas was the sole bacterial enteropathogen identified. Aeromonas was also isolated from 2 (0.5%) of 380 asymptomatic children. Despite its known lack of identifiable virulence properties, Aeromonas caviae was the most prevalent species, accounting for 69% of the isolates. None of the A. caviae strains produced cytotoxin by the 51Cr release assay and 12.5% were weakly enterotoxigenic by the infant mouse assay. All of the Aeromonas sobria and 71% of Aeromonas hydrophila were positive for both toxins. Ninety-two percent of the children with Aeromonas-associated diarrhea were younger than 3 years; 84% of the cases were seen between May and October. The majority of the children had an acute onset of watery diarrhea. Fever and vomiting were most commonly associated with the isolation of A. sobria. Eight children had chronic or intermittent diarrhea lasting for weeks to months before consultation; A. caviae was the isolate in all these cases. Several complications possibly related to Aeromonas intestinal infection were observed. These included Gram-negative bacteremia, intussusception, internal hernia strangulation, hemolytic uremic syndrome and failure to thrive in patients with chronic diarrhea. PMID- 3340461 TI - Viral and chlamydial etiology of acute infections of the lower respiratory tract in Colombian children. PMID- 3340462 TI - Aeromonas hydrophila wound infection in a patient with cyclic neutropenia following a piranha bite. PMID- 3340463 TI - Toxic shock syndrome associated with Staphylococcus aureus enterocolitis. PMID- 3340464 TI - Staphylococcus saprophyticus urinary tract infection in a sexually abused child. PMID- 3340466 TI - Acoustic reflectometry. PMID- 3340465 TI - Tuberculosis of the mandible: a case report. PMID- 3340467 TI - Neonatal sepsis screen. PMID- 3340468 TI - Behavioral pediatrics: a time for research. PMID- 3340469 TI - Pediatricians' opinions of mothers. AB - The purpose of this study was to determine factors that influence pediatricians' opinions of mothers. The degree to which mother-physician interactions, mother child interactions, and maternal demographic variables influence pediatricians' opinions of mothers was assessed with a 54-item questionnaire. Questionnaires were mailed to 470 Chicago-based American Academy of Pediatrics Fellows; 268 (57%) of the questionnaires were returned and, of these, 230 were suitable for analysis. A majority of pediatricians reported that their opinions were "greatly" positively influenced by mothers who communicate clearly (60%), understand recommendations (56%), follow recommendations (68%), and keep appointments (58%). In comparison, significantly fewer pediatricians' opinions were "greatly" influenced by mothers who are friendly to them (38%) or who like them (34%) (chi 2, P less than .001). Pediatricians were also "greatly" influenced by mothers who seem safety conscious (67%), use car restraints (57%), and keep immunizations updated (61%). Female pediatricians, in contrast to men, were significantly more influenced by mothers who "respond to their crying infants" and who "try to calm an anxious child" (chi 2, P less than .05). Pediatricians' opinions of mothers appear to be greatly influenced by maternal compliance, communications skills, and cognitive abilities, as well as by mothers who promote health and safety. Affective variables such as friendliness seem less important. Female pediatricians appear more influenced by mothers who actively console their children. PMID- 3340470 TI - Psychosocial functioning in children and young adults with juvenile arthritis. AB - A questionnaire survey of 363 children and young adults with juvenile arthritis was conducted to assess the relations among disease severity, psychosocial functioning, and adjustment in three age groups--primary school, high school, and young adult. Parents were surveyed separately to determine which characteristics of the ill child at different ages most significantly impact the well-being of the family. Indices of psychologic functioning and disease severity were associated with adjustment in the primary school and high school groups, whereas measures of social relationships were strongly associated with adjustment only in the high school group. Relations among measures of psychologic functioning, social relationships, disease severity, and adjustment in young adults were minimal. Level of disease severity was associated with the presence of financial concerns, emotional problems, and physical strain in parents of high school children and young adults. The results emphasize the importance of using a developmental model for understanding the adjustment of individuals with chronic juvenile arthritis and their families. PMID- 3340471 TI - Reducing nocturnal awakening and crying episodes in infants and young children: a comparison between scheduled awakenings and systematic ignoring. AB - Infants and toddlers (N = 33) exhibiting spontaneous awakening and crying episodes during the night were randomly assigned to one of three groups: scheduled awakenings, systematic ignoring or control. Scheduled awakenings consisted of a parent arousing and feeding or consoling the child 15 to 60 minutes before typical spontaneous awakenings. Once spontaneous awakenings were precluded, scheduled awakenings by parents were gradually eliminated. Systematic ignoring consisted of allowing the child to "cry it out" without parental attention except to ensure physical well-being of their child. Children in the scheduled awakening group and the systematic ignoring group awoke and cried less frequently than children in the control group during 8 weeks of treatment and during two follow-up checks, 3 and 6 weeks after treatment. Systematic ignoring was found to be more effective than the scheduled awakenings condition during 1 week of treatment; otherwise effects of the two conditions were similar. Implications of the use of these treatment procedures are discussed. PMID- 3340472 TI - Health concerns of high school students and teachers' beliefs about student health concerns. AB - Information about health concerns of adolescents can assist in assessment and treatment of their particular medical problems. Because teachers are important figures in the lives of young people, their beliefs about student health concerns are often solicited. A survey to assess adolescent health concerns and teachers' beliefs about student health concerns was conducted in two urban high schools on a sample of 831 students and 146 teachers. An assessment of 22 health concerns among the students revealed that a moderate level of concern existed on virtually every issue (the mean percentage "very concerned" was 55%), with black students and girls reporting more concern about many topics. In contrast, teachers significantly underestimated the level of concern of the students by an average of 13%, consistently having inaccurate beliefs about the types and level of student concerns. Students are concerned about health issues and are in need of health education and counseling in these areas. Teachers are not always aware of the level and types of student health concerns and may not be good sources of information about adolescent health. PMID- 3340473 TI - Childhood chronic disease and family functioning: a study of phenylketonuria. AB - Families with young children with phenylketonuria (n = 45) were compared with matched comparison families (n = 49) with respect to parental psychologic distress, marital satisfaction, parenting stress, family cohesion and adaptability, and child behavior. Multivariate analyses failed to show significant group differences. Univariate analyses indicated lower levels of adaptability and cohesion for the families with a child with phenylketonuria and evidence of lower levels of social competence in the children with phenylketonuria than in the comparison group. Group differences with regard to parental psychologic distress, marital satisfaction, and parenting stress were not found. The study results provide implications for understanding the impact of childhood chronic disease on families. PMID- 3340474 TI - Simultaneous administration of measles-mumps-rubella vaccine with booster doses of diphtheria-tetanus-pertussis and poliovirus vaccines. AB - The safety and efficacy of simultaneous administration of measles-mumps-rubella (MMR), diphtheria-tetanus-pertussis (DTP), and trivalent oral poliovirus (OPV) vaccines in a test group of 405 children were compared with the safety and efficacy of sequential administration of the same vaccines in a control group of 410 children given MMR followed by booster doses of DTP and OPV 2 months later. The study was double blind and placebo controlled with respect to DTP and OPV. Seroconversion rates to measles, mumps, and rubella exceeded 96% in both groups. Geometric mean titers to measles (P = .05) and rubella (P = .004) were higher in the test group, and titers of antibodies to the other seven antigens were similar in both groups. Clinical reaction data were analyzed in 248 of 405 test children and 249 of 410 control children. The rates of serious vaccine-associated reactions were low and similar in the two groups. Some minor side effects were reported more frequently in the test group, but these differences were judged to be related to study design rather than to differences in the safety of the two vaccine schedules. The results indicate that the safety and serologic efficacy of administering MMR simultaneously with reinforcing doses of DTP and OPV in the second year of life is equivalent to the safety and efficacy observed after administering these antigens separately. PMID- 3340475 TI - Injuries in youth football. AB - The injury experience of 5,128 boys (8 to 15 years of age, weight 22.5 to 67.5 kg [50 to 150 lb]) participating in youth football revealed an overall rate of significant injury of 5%, with 61% classified as moderate and 38.9% as major injuries. No catastrophic injuries occurred, and it was rare for a permanent disability to result from any injury. The upper extremity was most likely to be injured, and fractures were the most common injury to occur. The rate, site, and type of injuries experienced by the pre- and early adolescent players differed from the pattern for older players at higher levels of competition. Variables related to an increased risk of injury included participation in the older and heavier divisions, heavier weight, and involvement in contact activities. Factors associated with the occurrence of an injury were evaluated and provided areas for future study for the prevention of injuries. The medical care received by youth football participants was appropriate, although improved sideline surveillance for injured players is required. PMID- 3340476 TI - Homozygous protein C deficiency: observations on the nature of the molecular abnormality and the effectiveness of warfarin therapy. AB - An infant with severe homozygous protein C deficiency was brought to medical attention because of purpura fulminans and severe bilateral vitreous hemorrhages in the neonatal period. Infusions of fresh frozen plasma were given for 8 months. On two occasions, attempts to decrease the frequency of fresh frozen plasma infusions to less than twice a day led to episodes of microangiopathic hemolysis, fibrinolysis, and acute renal failure. Infarction of skin and subcutaneous tissues did not recur. Both episodes were controlled after reinstitution of fresh frozen plasma. Complications of therapy with fresh frozen plasma included hyperproteinemia and hypertension. Warfarin therapy was instituted when the baby was 8 months of age, followed by a gradual withdrawal of fresh frozen plasma therapy. The dose of warfarin required to maintain the prothrombin time in a range of 1.8 to 2.2 times normal varied considerably during short periods, a phenomenon that may have been due to several factors: hypercatabolism of the drug with prolonged administration, abnormality of liver function, variation in levels of serum albumin, fluctuations in drug dosage secondary to oral administration, and variations in dietary vitamin K. Protein C determinations by immunologic and functional assays consistently showed detectable but reduced protein C antigen levels with undetectable activity levels, suggesting that a dysproteinemia rather than a deficiency of synthesis is responsible for the child's coagulopathy. PMID- 3340477 TI - Early and late surfactant treatments in baboon model of hyaline membrane disease. AB - Because the issue of optimal time for artificial surfactant therapy for hyaline membrane disease has not been established, the effects of treatment with a reconstituted bovine surfactant (surfactant TA) were compared at two time periods in a hyaline membrane disease model in a premature baboon. The baboons were delivered by cesarean section at 75% of gestation (139.5 +/- 1.5 days, mean +/- SD). One group was treated with surfactant TA within ten minutes after birth (ultraearly), another group was treated at two hours of age (late) and a third (comparison group) did not receive the surfactant. Both treatment groups had significantly higher compliance and ratio of arterial to alveolar Po2 ratio and lower mean airway pressure and oxygen requirement (Fio2) than the comparison group. At autopsy, the largest residual volume and hysteresis in pulmonary pressure-volume curves were noted in the ultraearly group, intermediate values were found in the late group, and least values were found in the comparison group. These data indicate that early surfactant therapy for hyaline membrane disease results in greater improvement in lung mechanics than delaying treatment, even for two hours. Delivery room treatment with surfactant of infants at risk for hyaline membrane disease is perhaps better than therapy for established hyaline membrane disease. PMID- 3340478 TI - Right atrial thrombus formation screening using two-dimensional echocardiograms in neonates with central venous catheters. AB - Two-dimensional echocardiograms were used to prospectively screen 49 patients with 56 central venous catheters for right atrial thromboses from October 1985 to May 1986. All but four patients received a two-dimensional echocardiogram prior to insertion of the catheter. Once the catheters were in place, two-dimensional echocardiograms were performed no later than 3 weeks after insertion and then every 14 days until the catheter was removed. A single thrombus was detected 79 days after catheter placement (an incidence of 1.8%). Previous recommendations for weekly screening with two-dimensional echocardiogram were based on case reports alone. The 95% confidence limits for a negative two-dimensional echocardiogram result suggest that the initial two-dimensional echocardiogram screen for thrombus be obtained no sooner than 3 weeks after catheter insertion. In addition, significant gastrointestinal disease requiring operative intervention was present in 10 of 11 previous case reports as well as in our patient. Further studies with larger sample sizes are needed to determine whether subgroups of infants exist who are at a relatively higher risk for right atrial thrombus formation. PMID- 3340479 TI - Heredofamilial syndrome of mesodermal hamartomas, macrocephaly, and pseudopapilledema. AB - A 4 1/2-year-old boy with macrocephaly, pseudopapilledema, lipoangiomatosis, macropenia, and spotted pigmentations of the glans is reported. Lipoid masses were found in the subcutaneous tissue, tonsils, and probably the left lung. Some of these findings are consistent with features already reported by Riley and Smith, later by Bannayan, and recently by Ruvalcaba et al. We propose to unify the features of this syndrome and name it macrocephaly, hamartomas, and papilledema syndrome. The inheritance in our described case seems to be autosomal dominant. PMID- 3340480 TI - Parental attitudes about confidentiality in a pediatric oncology clinic. AB - Children and parents who attend pediatric oncology clinics often develop close relationships with other patients and may question clinic staff about another child's disease, therapy, or status. To assess parental attitudes concerning the dissemination of information by the clinic staff, questionnaires were mailed to the parents of all 154 patients who have attended pediatric oncology clinic since 1972. There were 100 (65%) responses including 77 from 99 living (78%) and 23 from 55 deceased patients (42%). Parents were asked whether clinic staff should respond completely to questions from other clinic parents regarding six aspects of their child's cancer. Percentages of parents who favored complete information sharing without their explicit consent about each of the aspects were as follows: diagnosis, 83%; medication/side effects, 85%; laboratory results, 66%; general status, 87%; occurrence of relapse, 77%; development of terminal phase, 67%. Neither the survival status (living v deceased) nor whether the patient was receiving therapy or not affected responses significantly. Benefit from receiving information about other children from clinic staff was reported by 82% of parents. PMID- 3340481 TI - New brain death guidelines in children: further confusion. PMID- 3340482 TI - Plastic handguns that resemble toy guns: new technology creates a uniquely hazardous product. PMID- 3340484 TI - American Academy of Pediatrics. Committee on Adolescence: Suicide and suicide attempts in adolescents and young adults. PMID- 3340483 TI - Right to refuse life-sustaining treatment. PMID- 3340486 TI - Nerds cereal and red stools. PMID- 3340485 TI - Anesthesia and intraventricular hemorrhage. PMID- 3340487 TI - Chloride-deficient formulas. PMID- 3340488 TI - Galactosemia--to screen or not to screen? PMID- 3340489 TI - Blood pressure cuff confusion. PMID- 3340490 TI - Vitamin E and retinopathy of prematurity. PMID- 3340491 TI - Bacteremia: occult or nonoccult? PMID- 3340492 TI - Vaginal discharge of 'beads' and the new diapers. PMID- 3340493 TI - The ratio principle holds over a million-to-one range of illumination. PMID- 3340494 TI - Infant timbre perception: discrimination of spectral envelopes. PMID- 3340496 TI - Ipsilateral and contralateral masking of duration. PMID- 3340495 TI - Cues to lexical choice: discriminating place and voice. PMID- 3340498 TI - Negative priming between response modalities: evidence for the central locus of inhibition in selective attention. PMID- 3340497 TI - Absolute phase uncertainty in sinusoidal grating detection. PMID- 3340499 TI - A phantom context effect: visual phantoms enhance target visibility. PMID- 3340500 TI - Quantitative relations between visual search speed and target-distractor similarity. PMID- 3340501 TI - Hess and Pretori revisited: resolution of some old contradictions. PMID- 3340503 TI - Viewing direction and pictorial representation. PMID- 3340502 TI - Responses by humans to oral chemical irritants as a function of locus of stimulation. PMID- 3340504 TI - Response-compatibility effects in focused-attention tasks: a same-hand advantage in response activation. PMID- 3340505 TI - Prediction of P-center location from the distribution of energy in the amplitude envelope: I. PMID- 3340506 TI - Perceived timing is produced timing: a reply to Howell. PMID- 3340507 TI - Prediction of P-center location from the distribution of energy in the amplitude envelope: II. PMID- 3340508 TI - The role of memory in perceiving subjective contours. PMID- 3340510 TI - The sum of induced and real motion is not a straight path. PMID- 3340509 TI - Reliability of psychophysical measures of gustatory function. PMID- 3340511 TI - On probabilistic categorization: the Markovian observer. PMID- 3340513 TI - When redundancy hurts letter detection: an attempt to define one condition. PMID- 3340514 TI - Evidence that brown is not an elemental color. PMID- 3340512 TI - Induction of rate-dependent processing by coarse-grained aspects of speech. PMID- 3340515 TI - Global and local processing by 3- and 4-month-old infants. PMID- 3340516 TI - Temporal integration of double electrical pulses. PMID- 3340517 TI - Apparent rotation in three-dimensional space: effects of temporal, spatial, and structural factors. PMID- 3340518 TI - Selective attention to global and local levels in the comparison of hierarchical patterns. PMID- 3340519 TI - Velocity or spatial and temporal separation: a comment on Farrell. PMID- 3340520 TI - A comment on "The effects of framing ratio and oblique length on Ponzo illusion magnitude". PMID- 3340521 TI - On analog movements of visual attention. PMID- 3340522 TI - Selective adaptation vs. transfer of decrement: the conjoint effects of neural fatigue and perceptual learning. PMID- 3340524 TI - Factor D is a selective single-stranded oligodeoxythymidine binding protein. AB - Factor D, a protein purified from rabbit liver that selectively enhances traversal of template oligodeoxythymidine tracts by diverse DNA polymerases, was examined for the sequence specificity of its binding to DNA. Terminally [32P] labeled oligomers with the sequence 5'-d[AATTC(N)16G]-3', N being dT, dA, dG, or dC, were interacted with purified factor D and examined for the formation of protein-DNA complexes that exhibit retarded electrophoretic mobility under nondenaturing conditions. Whereas significant binding of factor D to 5' d[AATTC(T)16G]-3' is detected, there is no discernable association between this protein and oligomers that contain 16 contiguous moieties of dG, dA, or dC. Furthermore, factor D does not form detectable complexes with the duplexes oligo(dA).oligo(dT) or poly(dA).poly(dT). The preferential interaction of factor D with single-stranded poly(dT) is confirmed by experiments in which the polymerase-enhancing activity of this protein is protected by poly(dT) against heat inactivation two- and four-fold more efficiently than by poly(dA) or poly(dA).poly(dT), respectively. PMID- 3340523 TI - Sequence and properties of the message encoding Tetrahymena hv1, a highly evolutionarily conserved histone H2A variant that is associated with active genes. AB - hv1 is a histone H2A variant found in the transcriptionally active Tetrahymena macronucleus, but not in the transcriptionally inert micronucleus. hv1 also contains antigenic determinants conserved in the histone complements of representatives of all four eukaryotic kingdoms. A cDNA clone encoding hv1 has been isolated and sequenced. Comparison of the derived protein sequence of hv1 with that of the chicken variant H2A.F and the sea urchin variant H2A.F/Z reveals remarkable homology in all but the extreme amino- and carboxy-termini and a small region in the conserved core. Putative regions of conserved antigenicity are discussed. Evidence is presented that suggests that hv1 is a single-copy, intron containing gene that encodes a polyadenylated message. Unusual features in the 3' flanking sequence and in codon usage are also described. Evidence is also presented showing that hv1 message amounts are ten-fold greater in growing cells than in starved cells. PMID- 3340525 TI - Topoisomer gel retardation: detection of anti-Z-DNA antibodies bound to Z-DNA within supercoiled DNA minicircles. AB - Small DNA fragments of approximately 350 bp in length, either with or without d(CG)n tracts, are ligated into underwound DNA minicircles to generate topoisomeric rings with different topological linking numbers, Lk. These minicircles, differing by an Lk of one, can be separated by acrylamide gel electrophoresis. Furthermore, electrophoresis can be used to reveal DNA double helix conformational changes that are induced by supercoiling, such as left handed Z-DNA. When anti-Z-DNA antibodies are added to such minicircles, their binding leads to a selective retardation of the electrophoretic migration of the Z-DNA containing circles. This effect is not seen with relaxed minicircles and those with insufficient torsional stress to induce a conformational transition. Thus the technique of 'topoisomer gel retardation' presents a very sensitive assay for the identification of proteins that selectively bind to DNA conformations stabilized by negative DNA supercoiling. PMID- 3340526 TI - Conformation of the synthetic DNA poly(amino2dA-dT) duplex in high-salt and aqueous alcohol solutions. AB - It has previously been demonstrated by other workers that the duplex of a synthetic DNA poly(amino2dA-dT) undergoes a salt-induced conformational isomerization. We show in the present work using circular dichroism that the same isomerization is induced in poly(amino2dA-dT) by various alcohols. The isomerization was originally identified as the B-to-Z and then B-to-A conformational transition of DNA but we demonstrate that the high-salt or alcohol conformation of poly (amino2dA-dT) is the non Z-DNA zig-zag double helix we have previously observed with poly(dA-dT) and called X-DNA. X-DNA is a cesium cation specific conformation of poly(dA-dT) while no similar cation specificity is observed with poly(amino2dA-dT). Thus it appears that the extra amino group attached to A and cesium cations make the same thing; they probably dehydrate the double helix minor groove and relieve its conformational variability. Poly(amino2dA-dT) is exceptionally stable in X-DNA and conditions inducing it are mild, which opens the door to assess its molecular structure. PMID- 3340527 TI - The complete nucleotide sequence of the potexvirus white clover mosaic virus. AB - The complete nucleotide sequence (5845 nucleotides) of the genomic RNA of the potexvirus white clover mosaic virus (WC1MV) has been determined from a set of overlapping cDNA clones. Forty of the most 5'-terminal nucleotides of WC1MV showed homology to the 5' sequences of other potexviruses. The genome contained five open reading frames which coded for proteins of Mr 147, 417, Mr 26,356, Mr 12,989, Mr 7,219 and Mr 20,684 (the coat protein). The Mr 147,417 protein had domains of amino acid sequence homology with putative polymerases of other RNA viruses. The Mr 26,356 and Mr 12,989 proteins had homology with proteins of the hordeivirus barley stripe mosaic virus RNA beta and the furovirus beet necrotic yellow vein virus (BNYVV) RNA-2. A portion of the Mr 26,356 protein was also conserved in the cylindrical inclusion proteins of two potyviruses. The Mr 7,219 protein had homology with the 25K putative fungal transmission factor of BNYVV RNA-3. PMID- 3340528 TI - Synthesis of DNA fragments containing 5,6-dihydrothymine, a major product of thymine gamma radiolysis. AB - 5,6-Dihydrothymine is one of the most important products of base damage by gamma irradiation of DNA in anoxic conditions. This modified base is unstable in the deprotection conditions used for classical synthesis of oligonucleotides. For its incorporation in synthetic DNA fragments, a new set of amino protecting groups has been developed. The 5,6-dihydrothymidine phosphoramidite was successfully employed for the synthesis of two 14-mers and one 17-mer bearing this defect at positions corresponding to restriction enzymes sites. The presence of the modified base still intact in the oligonucleotides was evidenced by mass spectrometry in pyrolytic conditions. PMID- 3340529 TI - Complete nucleotide sequence of a viroid isolated from Etrog citron, a new member of hop stunt viroid group. PMID- 3340530 TI - Nucleotide sequence of the frxB gene in wheat chloroplast DNA. PMID- 3340531 TI - Human pro alpha 1(I) collagen: cDNA sequence for the C-propeptide domain. PMID- 3340532 TI - Nucleotide sequence of the promoter region of the gene encoding chicken calbindin D28K. PMID- 3340533 TI - The nucleotide sequence of pACYC184. PMID- 3340534 TI - The nucleotide sequence of pACYC177. PMID- 3340535 TI - A correction in the nucleotide sequence of the Tn903 kanamycin resistance determinant in pUC4K. PMID- 3340536 TI - Complete cDNA sequence coding for human docking protein. PMID- 3340537 TI - Satellite II DNA of human lymphocytes: tandem repeats of a simple sequence element. PMID- 3340538 TI - Complete nucleotide sequence of the peroxisomal acyl CoA oxidase from the alkane utilizing yeast Candida maltosa. PMID- 3340539 TI - A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. PMID- 3340540 TI - The nucleotide sequence of 16S rRNA gene from Streptomyces lividans TK21. PMID- 3340541 TI - RY repeats are conserved in the 5'-flanking regions of legume seed-protein genes. PMID- 3340542 TI - Root nodule specific gene regulation: analysis of the soybean nodulin N23 gene promoter in heterologous symbiotic systems. AB - The nodulin N23 gene promoter was analysed in transgenic plants using the chloramphenicol acetyltransferase (CAT) coding sequence as a reporter. A 5' flanking region of less than 1 kb was sufficient for the organ-specific expression of a chimeric N23-CAT-3'lbc3 gene in root nodules formed on Lotus corniculatus and Trifolium repens after infection by their respective Rhizobium symbionts. Expression was regulated at the level of RNA in both species of transgenic plants. Promoter deletion analysis defined the 5' region required for high level expression and delimited two putative regulatory sequences involved in positive control of the N23 gene in L. corniculatus. PMID- 3340543 TI - Promoters of Mycoplasma capricolum ribosomal RNA operons: identical activities but different regulation in homologous and heterologous cells. AB - The 5' region of the rRNA operon, rrnA, of M. capricolum was cloned. Sequence analysis revealed two tRNA genes, tRNA(leu) and tRNA(lys), upstream to the promoter of the rRNA operon. The in vivo transcription start sites of the rRNA operon and of the tRNA genes were mapped. The same promoters used by M. capricolum RNA polymerase are also recognized by E. coli RNA polymerase both in vivo and in vitro. We find that high levels of ppGpp in E. coli, resulting from amino acid starvation or from spoT mutation, activate rather than repress the transcription of the mycoplasma rrnA operon. PMID- 3340545 TI - Analysis of conformational parameters in nucleic acid fragments. II. Co-crystal complexes of nucleic acid bases. AB - Studies have been made of conformational parameters in co-crystal complexes and compounds of nucleic acid bases in which there is the possibility of formation of hetero-base-pairs. Using published data extracted from the Cambridge structural database, a total of 37 base-pairs were found, of which 25 were hetero-pairs and 12 homo-pairs. These base-pairs were subject to analysis to reveal hydrogen bond parameters, propeller twist, buckle and C1'-C1' separation (or a similar parameter if C1' atoms were not present). Hetero-pairs were found to show larger twists than homo-pairs, the magnitude of twist being unrelated to hydrogen bond parameters or buckle value. The propeller twisting is less pronounced in these nucleic acid bases than in nucleosides, but still has a significant magnitude. Propeller twisting in hetero-pairs is found to be larger than in homo-pairs. Hetero-pairs appear to be formed preferentially in competitive situations. PMID- 3340544 TI - Organization, sequence and nuclease hypersensitivity of repetitive elements flanking the chicken apoVLDLII gene: extended sequence similarity to elements flanking the chicken vitellogenin gene. AB - Analysis of nuclease hypersensitivity of regions flanking the estrogen-dependent, chicken apoVLDLII gene has revealed an hepatic, DNaseI hypersensitive site whose sensitivity is influenced by both the developmental stage and sex of the bird. The site is located 3.0kb upstream from the gene, in a block of middle repetitive elements. Contact hybridization studies indicate that the block consists of contiguous copies of two elements with reiteration frequencies of 500-1000 and 10,000-30,000 copies per haploid genome. Sequencing of 1.8kb spanning the repeats has revealed that the higher frequency element is a member of the CR1 family. The adjacent lower frequency repeat can also be found next to another member of the CR1 family located in the 3' flanking region of the vitellogenin gene. The hypersensitive site has been mapped to one of the two most highly conserved regions of the CR1 element. This region displays homology with a silencer sequence recently identified in a CR1 element flanking the chicken lysozyme gene. PMID- 3340546 TI - Precise nucleosome positioning in the promoter of the chicken beta A globin gene. AB - Histone octamers were reconstituted onto 5' end-labelled DNA fragments derived from the promoter region of the chicken beta A globin gene. The location of the reconstituted histone octamer with respect to the DNA sequence of each fragment was assessed by Exonuclease III digestion of purified nucleosome monomers. By this approach we have found a strong preference for histone octamers to be positioned over nucleotides -206 to -62 relative to the gene cap site. This stretch of DNA contains all those 5' beta globin sequences which, by DNase footprinting, bind specific protein factors and incorporates three promoter consensus sequence motifs. The upstream terminal 32 base pairs of this DNA segment contains the binding sites for the erythrocyte specific G-string binding protein and transcription factor Spl and appears to be relatively weakly bound to the histone octamer. PMID- 3340547 TI - Identification of sequence-specific DNA-binding factors by label transfer: application to the adenovirus-2 major late promoter. AB - A method of affinity labelling proteins specifically associated with DNA target sequences is proposed. The method utilizes covalent UV-crosslinking of proteins to highly labelled DNA (e.g. in crude cell or nuclear extracts) followed by degradation of the DNA to short oligonucleotides. Proteins selectively labelled by attached residual oligonucleotides are readily amenable to molecular mass determination. Using this approach, we have characterized a HeLa polypeptide specifically bound to a short segment of the adenovirus-2 major late promoter (Ad2 MLP). A molecular mass value (approximately 51 kD) and precise location of the crosslinking site(s) of the protein within the MLP (-55 with respect to the cap site) were determined. PMID- 3340549 TI - A 13 bp palindrome is a functional estrogen responsive element and interacts specifically with estrogen receptor. AB - Sequences located upstream of the transcription initiation site of the Xenopus vitellogenin A2 (vit A2) gene contain a hormone dependent enhancer that confers estrogen control to the heterologous thymidine kinase (tk) promoter. As a minimal functional estrogen responsive element (ERE), we have defined the 13 bp palindrome GGTCACAGTGACC. This ERE binds estrogen receptor preferentially in vitro. Although the ERE shares some structural features with the glucocorticoid responsive element (GRE) it is distinct from this element since it neither binds glucocorticoid receptor in vitro nor does it confer glucocorticoid inducibility to a fusion gene. Point mutations within the ERE decrease its affinity for the estrogen receptor and result in a complete loss of estrogen inducibility. PMID- 3340550 TI - Comparative calorimetric studies on the dynamic conformation of plant 5S rRNA. I. Thermal unfolding pattern of lupin seeds and wheat germ 5S rRNAs, also in the presence of magnesium and sperminium cations. AB - An attempt has been made to correlate differential scanning calorimetry melting profiles of 5S rRNAs from lupin seeds (L.s.) and wheat germ (W.g.) with their structure. It is suggested that the observed differences in thermal unfolding are due to differences in RNA nucleotide sequence and as a consequence in higher order structures. Interesting effects induced by magnesium cation, perprotonated and permethylated sperminium tetracations are discussed. It is suggested that the difference in the stabilizing effect of the three cations results from different mode of their interactions with RNA. "Pure" electrostatic interactions expected for permethylated tetracations are rather weak due to the steric hindrance around each positively charged nitrogen atom. Electrostatic interactions of the other two cations are significantly enhanced by coordination bonding for magnesium and by hydrogen bonding for protonated sperminium cation. PMID- 3340548 TI - Molecular cloning of chicken metallothionein. Deduction of the complete amino acid sequence and analysis of expression using cloned cDNA. AB - A cDNA library was constructed using RNA isolated from the livers of chickens which had been treated with zinc. This library was screened with a RNA probe complementary to mouse metallothionein-I (MT), and eight chicken MT cDNA clones were obtained. All of the cDNA clones contained nucleotide sequences homologous to regions of the longest (376 bp) cDNA clone. The latter contained an open reading frame of 189 bp, and the deduced amino acid sequence indicates a protein of 63 amino acids of which 20 are cysteine residues. Amino acid composition and partial amino acid sequence analyses of purified chicken MT protein agreed with the amino acid composition and sequence deduced from the cloned cDNA. Amino acid sequence comparisons establish that chicken MT shares extensive homology with mammalian MTs, but is more closely related to the MT-II than to the MT-I isoforms from various mammals. The nucleotide sequence of the coding region of chicken MT shares approximately 70% homology with the consensus sequence for the mammalian MTs. Southern blot analysis of chicken DNA indicates that the chicken MT gene is not a part of a large family of related sequences, but rather is likely to be a unique gene sequence. In the chicken liver, levels of chicken MT mRNA were rapidly induced by metals (Cd2+, Zn2+, Cu2+), glucocorticoids and lipopolysaccharide. MT mRNA was present in low levels in embryonic liver and increased to high levels during the first week after hatching before decreasing again to the basal levels found in adult liver. The results of this study establish that MT is highly conserved between birds and mammals and is regulated in the chicken by agents which also regulate expression of mammalian MT genes. However, in contrast to the mammals, the results suggest the existence of a single isoform of MT in the chicken. PMID- 3340551 TI - High level expression and purification of HhaI methyltransferase. AB - A cloning system for the DNA-(cytosine-5)-methyltransferase MHhaI and high level expression of the enzyme are described. A parent plasmid was constructed from fragments of the MHhaI gene and synthetic oligonucleotides. The construct permits introduction of various restriction sites for cloning at precise positions near the initiation codon, and beyond the termination codon. The entire MHhaI coding sequence was introduced as a 1042 b.p. NdeI-XbaI fragment into the vector pAR3040 which contains the T7 RNA polymerase promoter. The resultant plasmid pTNX3 (MHhaI pAR3040) was introduced into McrB- E. coli strains HB101 and GM2929, and expression of MHhaI was induced by infection with the lambda phage CE6 carrying the T7 RNA polymerase gene. In induced cells, catalytically active MHhaI was produced at a level that corresponds to about 8% of the total soluble protein; an insoluble form of the protein was also formed, but could be readily removed. The expressed soluble enzyme from HB101/pTNX3 was purified to apparent homogeneity in about 50% yield by a two-step chromatographic procedure involving DEAE-cellulose and Heparin-Sepharose; a one liter culture gave about 2.5 mg of pure enzyme. The molecular weight and kinetic properties of the expressed protein are identical to those reported for the authentic MHhaI, and its amino terminal sequence agrees with that predicted from the DNA sequence. PMID- 3340552 TI - CD of six different conformational rearrangements of poly[d(A-G).d(C-T)] induced by low pH. AB - On the basis of circular dichroism (CD) data, we have now identified six different conformational states (other than the duplex) of poly[d(A-G).d(C-T)] at pH values between 8 and 2.5 (at 0.01M Na+; 20 degrees C). Three of these structural rearrangements were observed as the pH was lowered from 8 to 2.5, and three additional rearrangements were observed as the pH was raised from 2.5 back to neutral pH. The major components of the six conformational states were defined using appropriate combinations of the CD spectra of the duplex, triplex, and denatured forms of this polymer, as well as the CD spectra of the individual single strands and their respective acid-induced self-complexes. Our results show that the acid-induced rearrangements of poly[d(A-G).d(C-T)] include not only the poly[d(C+-T).d(A-G).d(C-T)] triplex, but also include the poly[d(C-T)] loop-out structure and a self-complexed form of the poly[d(A-G)] strand that is pH dependent. PMID- 3340553 TI - The F-type 5' motif of mouse L1 elements: a major class of L1 termini similar to the A-type in organization but unrelated in sequence. AB - It has previously been shown that the L1 family in the mouse (L1Md) contains two alternative 5' ends called the A- and F-type sequences (1,2). We show here that the F-type element is a major class of murine L1 elements and report on the details of organization of the 5' motif of these F-type elements. Although the A- and F-type 5' sequences share no detectable sequence homology the organization of an F-type 5' end is strikingly similar to that of an A-type. That is, the F-type 5' sequences consist of a tandem array of a small number of 206 bp monomers while the A-type 5' motif consists of a tandem array of 208 bp monomers. All of the A type elements characterized to date have a truncated monomer at the 5' end of the array. Many of the F-type elements are also terminated at the 5' end by a truncated copy but unlike the A-type elements some F-type elements terminate with a monomer which is within a few nucleotides of being complete. In addition the F type consensus sequence, in contrast to the A-type sequence, shows homology (70%) to the body of the L1Md starting at the position where the monomer joins the rest of the L1 element. PMID- 3340554 TI - A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes. AB - The interaction of calf-thymus DNA with Cu(II) and Pb(II) ions has been investigated in H2O and D2O solutions at physiological pH, using laser Raman spectroscopy. The results confirm the destabilizing effect of Cu2+ ions, which are shown to bind strongly to the guanine and cytidine bases, perturbing the A-T base pairs and disrupting the double-helical structure of DNA, whose conformation is markedly altered by these interactions. Earlier claims that Pb2+ ions destabilize DNA are not supported by the present study. These ions are found to interact only weakly with the nucleic bases, binding to the N7 position of the guanine bases and also interacting with the A-T pairs. Both types of ions are found to interact with the charged phosphate groups of DNA, although these sites are preferred over the nucleic bases by Pb2+ ions. PMID- 3340555 TI - Intracisternal A particle gene related sequences are present in multiple copies in normal tissues and tumors of Mastomys natalensis (Muridae). PMID- 3340556 TI - Inexpensive and simple set-up for field inversion gel electrophoresis. PMID- 3340557 TI - Construction of novel eukaryotic transfection-vector, pJNL-1. PMID- 3340558 TI - Human tRNASer gene organization and a tRNASer gene sequence. PMID- 3340559 TI - Resolution of sequence discrepancies in the ORF1 region of the Kluyveromyces lactis plasmid k1. PMID- 3340560 TI - Two mRNAs of mouse pro alpha 1(I) collagen gene differ in the size of the 3' untranslated region. PMID- 3340561 TI - A Sephadex column procedure for DNA isolation is also useful for detecting dsRNA. PMID- 3340563 TI - The ethic of caring: has it been discarded? PMID- 3340562 TI - Nucleotide sequence of the LuxA and LuxB genes of the bioluminescent marine bacterium Vibrio fischeri. PMID- 3340564 TI - Doctoral education: our claim to the future. PMID- 3340565 TI - Using research to shape health policy. AB - Nursing science and research findings are powerful ingredients in influencing health care policy makers. Policy must be influenced on several levels: practice, the environment of practice, and public policy. Nursing has successful examples of the benefits of such efforts. Doctoral students, as the future nurse scientists of our discipline, must be socialized to value and understand the process of using the profession's research base to affect health care policy at numerous levels. Nursing knowledge of these strategies and the theoretical bases undergirding them has only begun to develop. Our challenge is to develop such strategies more systematically based on the growing body of knowledge in health care policy that relates to nursing science and research. PMID- 3340566 TI - At the faultline: social activism and caring. PMID- 3340567 TI - A different kind of nursing. PMID- 3340568 TI - For want of a mentor.... PMID- 3340569 TI - Learning on the road: nursing in the British Isles and Ireland. PMID- 3340570 TI - The ethic of caring: can it survive in nursing? PMID- 3340571 TI - Development of a measure of learned helplessness. AB - The purpose of this study was to develop a measure of learned helplessness. Based on a review of the literature, 50 items were developed for inclusion in the proposed Learned Helplessness Scale (LHS). On the basis of independent reviews by three experts, 20 items were selected for inclusion in the LHS. An individual's response to each item was graded, using a Likert scale. A standardized alpha reliability coefficient of .85 was obtained for a sample of 241 healthy adults. There was a positive correlation between the LHS scores and Beck's Hopelessness Scale (HS) scores (r = .252) and a negative correlation between the LHS scores and Rosenberg's Self-Esteem Scale (SES) scores (r = -.622). These correlations were in the direction postulated by various theorists. A Varimax-rotated factor analysis of the LHS data yielded five factors. Three of these factors tapped content relevant to the attributional styles of learned helplessness. Clinical data were also obtained on samples of oncology, hemodialysis, and spinal cord patients. Because the alpha reliability coefficients of the LHS and the Pearson product moment correlation coefficients between the LHS and the HS and the LHS and the SES were in the same direction, the instrument is believed to have adequate internal consistency. PMID- 3340572 TI - Development of an instrument to measure stress in the older adult. AB - The purpose of this study was to develop and carry out initial psychometric evaluation of a tool to measure stress in adults 65 years of age and older. The universe of stressors for this age group was elicited from 25 older adults, a literature review, and consultations with gerontological nursing experts. The stressors were ranked and weighted, using a Q-sort, by a sample of 43 adults 65 and over, resulting in the Stokes/Gordon Stress Scale (SGSS). The instrument was evaluated using reliability and validity measures. Test-retest reliability estimates yielded a Pearson's r ranging from .98 to .90. Coefficient alpha was .86. Pearson's r in a 1-year test of predictive validity was .36, p = .014; in tests of concurrent validity correlations ranged from .65 to .81. The SGSS can be used for clinical and research purposes to aid in assessing and planning care for the older individual. PMID- 3340573 TI - Primiparas' prenatal concern for learning infant care. AB - The purpose of this study was to determine if there are differences in pregnant women's desire to learn infant care during the antepartal period. Desire to learn infant care was defined as (a) learning about practical aspects of infant care and (b) expressing the desire to become a caring mother. One hundred eighty-nine primiparous women were interviewed using an open-ended interview schedule. Responses were audiotaped and transcribed prior to data analysis. Each subject's interview transcript was categorized according to content related to desire to learn infant care and converted to a proportion that reflected the amount of desire to learn infant care as compared to the amount of total concern the subject addressed. The proportion scores representing three stages of the antepartal period were compared for statistical differences. Significant differences were found for overall desire to learn infant care and for the desire to learn infant care skills among the three stages of the antepartal period. No significant differences were found for desire to become caring mother. Effects of socioeconomic status, previous early terminated pregnancy, and child care experience were explored. PMID- 3340575 TI - On babies and bathwater. PMID- 3340576 TI - Mental distress and recovery in a high-risk bereavement sample three years after untimely death. AB - Recovery from postdisaster bereavement was the primary concern of this longitudinal study: would levels of mental distress and recovery reported 1 year following a natural disaster be better predictors of mental distress and recovery reported 3 years postdisaster than demographic variables, concurrent life stress, and mediating factors? The 119 bereaved and control participants studied in 1981, one year following the 1980 volcanic eruption of Mount Saint Helens, were recontacted in 1983; of these, 85 consented to follow-up. The 1983 data collection consisted of identical measurement tools and procedures used in 1981. Three regression analyses addressed prediction of mental distress and recovery. The first two analyses compared disaster-bereaved and nondisaster-loss controls; the third pertained only to the bereaved. For the bereaved/control comparisons, 1981 levels of mental distress, age, sex, education, and 1983 levels of negative life stress, self-efficacy, and social support were predictors of the dependent variable, mental distress. For the bereaved group, 1981 mental distress and 1983 self-efficacy scores were the only significant predictors of 1983 mental distress. In the control group, two additional variables, sex and concurrent negative life stress, were also significant predictors of 1983 mental distress. In the final regression analysis, predictors of self-rated recovery, importance of the deceased person rated by the bereaved 1 year postdisaster, and beliefs of preventability of death reported 3 years postdisaster were predictors of 1983 recovery. Only importance of the deceased person was a significant predictor in the latter analysis. Results suggest that recovery is a lengthy process and that much remains to be learned about influencing factors. PMID- 3340577 TI - Bottle- and breast-feeding: effects on transcutaneous oxygen pressure and temperature in preterm infants. AB - Transcutaneous oxygen pressure (tcPO2) and body temperature were monitored for the duration of feeding sessions in five small preterm infants who served as their own controls for bottle-feeding (BoF) and breast-feeding (BrF). Longitudinal data were collected twice weekly for BoF and BrF sessions from infants' first oral feeding until discharge, for a total of 71 feeding sessions: 32 BoF and 39 BrF. Markedly dissimilar for the two feeding methods, tcPO2 patterns suggested less ventilatory interruption during BrF than BoF. Sequential tcPO2 values at baseline, immediately postfeed, and 10 minutes postfeed were significantly different for the feeding methods, with greater declines for BoF. Maximal temperature change, calculated by subtracting the baseline from the most extreme temperature for each feeding session, indicated that infants became significantly warmer during BrF than BoF. Although the small sample size necessitates replication, these results do not support the widely held assumption that BrF is more stressful than BoF for small preterm infants. PMID- 3340578 TI - Use of the Piers-Harris Self-Concept Scale with Indian children: cultural considerations. AB - Data from a survey of 241 Montana school children, Indian and white, were used as a basis for examining the psychometric properties of the Piers-Harris Self Concept Scale. Strong estimates of internal consistency and support for construct validity were found. Studies using the Piers-Harris scale over the past 15 years have indicated that ethnic minority status per se is not related to lower self concept score and that the scale is a reliable measure for use with minority group children. However, validity of the scale with Indian children warrants further examination, particularly in relation to the differential effects of ethnic culture and social environment on the measurement of self-concept. PMID- 3340574 TI - Self-reported factors influencing exercise adherence in overweight women. AB - The purpose of this study was to determine the effect of intensity-controlled, graded dance exercise and selected components of behavior modification on exercise adherence in overweight middle-aged women. Thirty-eight moderately overweight women, aged 35 to 58, participated in a 16 1/2 week dance exercise program. Participants were randomly assigned to an experimental group (n = 20) that received intensity-controlled, graded exercise and individual and group reinforcement, or to a control group (n = 18) that exercised at a moderate intensity typical of commercial fitness classes and received no special reinforcement. Before exercise training began and at the completion of 16 1/2 weeks, a structured, open-ended interview was conducted. Ninety-four percent of the women in both groups adhered to the program, an exceptionally high adherence rate for this population. Eight participant-identified factors seemed to have influenced exercise adherence: group homogeneity, carpooling and social networks, pleasurable feelings associated with increased energy and fitness, leader with a health-related background, time limitation of exercise program, commitment to an established goal, desire to change body image, and desire to change health status and improve physical health. PMID- 3340579 TI - Interrater reliability decline under covert assessment. AB - This article highlighted representative studies on a methodological problem that may generalize to other observational methods and circumstances. A number of strategies have been suggested to combat this problem. Despite the need for additional research on this methodological problem and the remedial tactics discussed here, studies that deal with interrater reliability decline will surely be evaluated as more credible than those that overlook the problem. PMID- 3340580 TI - Collaborative research and authorship credit: beginning guidelines. PMID- 3340581 TI - Reliability in category coding systems. PMID- 3340582 TI - Experiencing the research process by using statistical software on microcomputers. PMID- 3340583 TI - Development of an instrument to measure hope. AB - The purpose of this study was to develop an instrument to measure hope in adults and to evaluate its psychometric properties. A 40-item Miller Hope Scale (MHS) was developed based on critical elements of hope revealed in a comprehensive review of the literature and on an exploratory study of hope in persons who survived a critical illness. The instrument was critiqued by measurement and content experts, and content validity was established. The MHS was pretested on 75 subjects. The refined instrument was next evaluated using 522 healthy adults. The intent was to establish norms on the instrument before using it on ill subjects. The range of scores on the MHS is 40 to 200, with high scores indicating high hope. Mean hope score for this healthy sample was 164.46 (SD = 16.31). A leptokurtic curve, skewed to the left, was noted in these responses. As expected, the instrument detected high hope in individuals who were screened to have no physical or mental health problems. The internal consistency alpha coefficient was .93 with a 2-week test-retest reliability of .82. Criterion related construct validity was established by correlating the MHS to the Psychological Well-Being Scale, r = .71, the Existential Well-Being Scale, r = .82, and a 1-item hope self-assessment, r = .69. Divergent validity with the Hopelessness Scale was established, r = -.54. Maximum likelihood factor analysis with oblimin rotation resulted in a three-factor solution: I, Satisfaction with Self, Others, and Life; II, Avoidance of Hope Threats; and III, Anticipation of a Future. PMID- 3340584 TI - Nursing research and AIDS. PMID- 3340585 TI - The name game. PMID- 3340587 TI - Sweet charity? PMID- 3340586 TI - Health visitors or child police? PMID- 3340588 TI - Children of the ghetto. PMID- 3340589 TI - Dangerous traffic. PMID- 3340591 TI - No sex, please, we're over 60. PMID- 3340590 TI - Joint appointments: handle with care. PMID- 3340592 TI - Making the numbers add up. PMID- 3340594 TI - Nursing for non-achievers. PMID- 3340593 TI - Water baths for pain relief in labour. PMID- 3340596 TI - Code of conduct. The furniture that led to a fall. PMID- 3340595 TI - What are nurses like? PMID- 3340597 TI - Patients' sleep-wake rhythms in hospital. Part 1. PMID- 3340598 TI - Ankle fracture. PMID- 3340599 TI - Mental handicap nursing. PMID- 3340600 TI - Mental handicap nursing. Positive planning. PMID- 3340601 TI - Mental handicap nursing. Be prepared. PMID- 3340602 TI - Mental handicap nursing. Wish you were here? PMID- 3340604 TI - Not the flu! PMID- 3340603 TI - Depression. Management tips for the primary care physician. AB - Treatment of major depression can in most cases be handled by the primary care physician who is willing and able to take the time. The minority of patients who pose particular problems in diagnosis or treatment should be referred to a psychiatrist. Primary care physicians are encouraged to regard major depression as being as much within their scope as other common disorders. After pharmacotherapy and office counseling, some patients may need psychotherapy to help them alter patterns of thinking and interaction that contribute to depression. PMID- 3340605 TI - Genital herpes. Recommendations for comprehensive care. PMID- 3340606 TI - Burning and pain after injury. Is it causalgia or reflex sympathetic dystrophy? PMID- 3340607 TI - Independent, chain, or mail-order pharmacy. Where do patients have their prescriptions filled? PMID- 3340608 TI - Cystic fibrosis, independence, and tae kwon do. If you dream it, you can do it. PMID- 3340609 TI - Falls in the elderly. Is prevention possible? AB - Many elderly persons who fall have multiple problems, which often present in a nonspecific manner. Identification of the cause of the falls is not always possible but is well worth attempting in view of the often disastrous consequences. Because the home is the most common site of falls, various safety measures are recommended to help compensate for the normal frailties of aging. PMID- 3340610 TI - Subclavian steal syndrome. A report of two cases. AB - Two cases of subclavian steal syndrome are reported. Symptoms included light headedness or syncope, reflecting vertebrobasilar insufficiency, and in one case, numbness and tingling in the left upper extremity, reflecting ischemia. Many persons with this syndrome are asymptomatic. Key findings include unilaterally decreased pulses and a significant difference in blood pressure between the upper extremities. Arch aortography, the "gold standard" of diagnosis, must be performed before surgical intervention. PMID- 3340611 TI - Effects of PGE1 alone and on sympathetically mediated Na, K transport in the perfused main submandibular duct of rat. AB - PGE1 was administered in 5 micrograms/kg doses every 5 min over a period of 70 min and Na and K transport in the perfused main duct of rat submandibular gland was examined during a period without stimulation of the sympathetic nerve as well as during stimulation of the sympathetic nerve. A 25% decrease in the amount of Na absorbed and a 42% decrease in the amount of K secreted occurred when PGE1 alone was administered; the same change occurred when the sympathetic nerve was stimulated in the presence of PGE1. These data show, for the first time, an effect of PGE1 alone on electrolyte transport, and suggest that specific PGE1 receptors are activated. PMID- 3340612 TI - Intestinal accumulation of lead salts and milk lead by suckling rats. AB - Absorption of lead is known to be enhanced during infancy. In this study, the sites of intestinal accumulation of Pb by suckling rats have been determined under various conditions using 203Pb as a tracer. When 203Pb was administered intragastrically (IG) as a soluble salt, accumulation occurred primarily in the duodenum, regardless of dose and vehicle. In contrast, when rat pups suckled from a dam which had received 203Pb, the only region of the small intestine showing accumulation of radioactivity was the ileum. To confirm that these differences were not related to the route of administration, rat milk was labeled with 203Pb and was then used for IG administration. Once again, accumulation (4 hr post administration) was confined to the ileum. When the dose was increased 10-fold, milk Pb displayed some accumulation in duodenal tissue, but very much less than that of soluble Pb at the same time and dosage. At 20 hr postadministration, there was negligible 203Pb in any region of the small intestine following administration as a soluble salt, but substantial retention in ileal tissue following administration in milk. The strikingly different patterns of intestinal accumulation obtained with Pb salts as compared with milk Pb suggest different modes of absorption of Pb ingested in these two forms. PMID- 3340613 TI - Protection against hyperoxia by serum from endotoxin treated rats: absence of superoxide dismutase induction. AB - Endotoxin greatly reduces lung injury and pleural effusions in adult rats exposed to normobaric hyperoxia (greater than 98% oxygen for 60 hours). This study reports that serum from endotoxin treated donor rats protects serum recipients against hyperoxic lung injury without altering lung superoxide dismutase (SOD) activity. Rats pretreated with endotoxin alone were protected and exhibited an increase in lung SOD activity as previously reported by others. Protection by serum was not due to the transfer of residual endotoxin or SOD. These results show that protection from oxygen toxicity can occur in rats without an increase in lung SOD and suggest that a serum factor may be involved. PMID- 3340614 TI - A differential action for ethanol on baroreceptor reflex control of heart rate and sympathetic efferent discharge in rats. AB - The acute effects of ethanol (0.33, 0.66, or 1 g/kg) on baroreflex control of heart rate (HR) and sympathetic efferent discharge (SED) were investigated in chloralose-anesthetized rats. The two higher doses of ethanol caused a progressive and significant increase in baseline SED and a slight increase in HR. That these effects were ethanol mediated is suggested by the absence of any change in blood pressure following ethanol injection in any amount used and the finding that equivolume saline had no effect on any of the tested parameters. On the other hand, the baroreflex slope of the MAP-SED relationship after ethanol was similar to the control (preethanol) value in contrast to a significant decrease in the baroreflex slope of MAP-HR under the same conditions. These findings suggest that the sensitivity of the reflex control of SED was preserved whereas that of HR was impaired after acute ethanol administration. Since these findings were obtained in the same animals, our data suggest that acute ethanol has a differential action on reflex control of SED and HR. Further, the significant increase in SED after moderate and high doses of ethanol suggests an increased central sympathetic tone as recordings were made from preganglionic nerve fibers (splanchnic nerve). The absence of an increase in baseline MAP, in spite of a significant increase in baseline SED following acute ethanol injection, could be explained, at least in part, by an ethanol-evoked reduction in pressor responsiveness to phenylephrine, an alpha-adrenergic agonist. PMID- 3340616 TI - Leucine catabolism and incorporation into tissue proteins in thyroparathyroidectomized rats. AB - We investigated parameters of leucine metabolism in thyroparathyroidectomized (TPX) and pair-fed control rats using a technique of continuous infusion of [l 14C]leucine. The rate of leucine turnover was significantly smaller in TPX than in control rats (42.5 +/- 2.6 vs 35.1 +/- 1.9 mumole/hr/100 g, mean +/- SEM, six rats). There was no significant difference between rates of alpha-decarboxylation of leucine by the two groups of rats. The protein incorporation of leucine was significantly smaller in the muscle of TPX than control rats (39 +/- 5 vs 24 +/- 4 pmole/mg protein, mean +/- SEM, six rats) but in liver it was not significantly different. Thyroparathyroidectomy also had no significant effect on concentration of either leucine or its ketoacid (alpha-ketoisocaproate) in plasma, liver, and muscle. We conclude that hypothyroidism does not alter catabolism of leucine but reduces its incorporation into muscle protein. PMID- 3340615 TI - Toxic effect of lithium in mouse brain. AB - The effect of lithium ion on glucose oxidation in the cerebrum and cerebellum of mice was measured in vitro by the conversion of isotopic glucose into 14CO2/mg wet weight. Glucose utilization is unaffected by lowest lithium dosage but is inhibited by high lithium concentrations (197-295 mM). Chronic administration of lithium to adult mice decreased the DNA content of the cerebrum and cerebellum at concentrations of 80 and 108 mM. The DNA content of selected postnatal stages of cerebrum and cerebellum was measured starting on Day 1 or 2. This served as another parameter to evaluate glucose oxidation studies at these ages. On the basis of wet weight, both brain parts of neonates of ages 1 and 10 days were approximately one-half that of the adult counterparts. On the basis of DNA content, the cerebrum enhanced its glucose utilization twofold from Day 1 to Day 10 and tripled its utilization from Day 10 to Day 20. The glucose utilization by cerebrum at Day 20 is similar to adult values. In contrast, glucose oxidation in the cerebellum remained relatively constant throughout the postnatal growth. The relative susceptibility of the two brain parts is discussed. PMID- 3340617 TI - Copper deficiency and tissue glutathione concentration in the rat. AB - Copper deficiency in rats increased renal vein and arterial (heart) plasma GSH concentration by approximately 50%. There was no change in plasma GSSG concentration. Renal vein plasma GSSG/GSH ratio was decreased in copper deficiency, which is consistent with previous reports showing a copper-dependent thiol oxidase activity in the renal basement membrane. No change occurred in arterial plasma GSSG/GSH ratio. Hepatic GSH concentrations were also elevated by 50% in copper deficiency, GSSG concentrations were unaffected, but GSSG/GSH ratio was depressed. Renal and cardiac tissue GSH and GSSG were unaffected by copper deficiency. The decreased SOD activity and GSH-Px activity observed in copper deficiency may contribute to increased hepatic and plasma GSH concentrations. PMID- 3340618 TI - Bioavailability of copper to rats from various foodstuffs and in the presence of different carbohydrates. AB - Copper bioavailability was studied in rats using an extrinsic Cu label. Copper absorption from sunflower seeds (46%), peanuts (41%), cooked shrimp (50%), and cooked beef (40%) was as good or better than copper sulfate (46%). Copper from plant foods (sunflower seeds, garbanzo beans, peanuts) was absorbed equally as well as copper from animal foods (beef, shrimp, chicken liver), 39 +/- 7% vs 43 +/- 7%, P greater than 0.05. There was no significant difference in percentage Cu absorption between intrinsically labeled chicken liver and extrinsically labeled chicken liver. In a second experiment, Cu absorption was measured in the presence of glucose, fructose, sucrose, or cornstarch. There were no significant differences in Cu absorption due to different carbohydrates in a single meal. PMID- 3340619 TI - Central sympathoplegic and norepinephrine-depleting effects of antioxidants. AB - Carbon disulfide (CS2), tetraethyl lead (TEL), tetraethyl tin (TeET), dithiothreitol (DTT), and gossypol acetic acid (GAA) significantly decreased brain norepinephrine (NE) in rats. The central dopamine (DA) increased after ip administration of CS2, TEL, and DTT, but decreased after TeET and GAA. The brain serotonin decreased only after TeET. Two doses of DTT decreased the NE longer than one dose (24 vs 2 hr) but did not increase DA. L-DOPA, given SC with DTT, delayed the decrease in NE by 24 hr. The similar behavioral and autonomic effects of each of these compounds suggest a central sympatholytic effect and an antipsychotic type of sedation and rigidity. A possible mechanism is reversible inhibition of dopamine beta-hydroxylase through the reduction of the copper ion of the enzyme. Each of these reducing agents, together with the boranes previously studied, has similar behavioral and autonomic effects and a common effect on NE concentration, suggesting that the agents act through a physicochemical property rather than by combination with a cellular component. These data have applications to the toxicity of the single agents. They also provide an index of activity, previously lacking, of systemic antioxidant effect. PMID- 3340621 TI - Rat placental luteotropin: initial secretion and luteolytic quality. AB - The secretion of placental lactogen begins early in pregnancy. Previous studies indicate that rat placental lactogen (rPL) is secreted from Day 8 of pregnancy and that it is luteolytic as well as luteotrophic. This study establishes the onset of both the luteotrophic and the luteolytic effects of placental lactogen in pregnant rats subject to timed hypophysectomy. Pregnancy was preserved in all groups with the administration of dydrogesterone (9 beta, 10 alpha-pregna4,6 diene-3, 20 dione), a progesterone analog, and diethylstilbestrol, an estrogen analog. Plasma progesterone and 20 alpha-hydroxypregn-4-ene-3-one (20-OHP) were measured in serial serum samples by RIA. The data indicate that rPL is secreted as early in pregnancy as the seventh day. Rats hypophysectomized on Day 6 of pregnancy or later had ovaries that contained corpora lutea that secreted increasing quantities of progesterone during pregnancy. On Day 16 serum progesterone values were lowest in animals operated on Days 4 and 5 compared to animals operated on Days 6 or 8. The 20-OHP serum values from animals operated on Days 4 and 5 declined steadily from Day 8 to Day 16. These findings indicate progestational incompetency, which was confirmed morphologically. Thus, rPL secretion begins by Day 7 and it is both luteotrophic and luteolytic. PMID- 3340620 TI - The mechanism of peroxidase-mediated cytotoxicity. II. Role of the heme moiety. AB - Various peroxidases in the presence of hydrogen peroxide and a halide ion have been shown to exert a cytolytic activity against erythrocytes and other cells. However, few studies have been done to elucidate the active site on the enzymes that is responsible for the cytotoxic activity. In addressing this question we found that boiling of horseradish peroxidase only partially abolishes its cytotoxic activity, suggesting that an intact tertiary structure of the protein may not be essential for the cytotoxic activity. This conclusion was confirmed by demonstrating that microperoxidase, hemin, and hematoheme also exert cytotoxic activity in the presence of hydrogen peroxide and iodide, the kinetics of which were identical to those obtained with the peroxidases. Fluoride, bromide, and thiocyanate could not replace iodide in any of these systems. These results indicate that the active site for the cytotoxic activity of the peroxidases is located within the heme moiety, whereas the protein portions of the enzymes affect the cytotoxic activity of the enzymes only in an indirect manner. We also tested a variety of compounds for their ability to inhibit the cytolytic reaction toward erythrocytes. We found that compounds such as thiourea, thionicotinamide, and uric acid are much more potent inhibitors of the cytolytic reaction than tyrosine and histidine. These observations support the concept that oxidative reactions rather than halogenation reactions are the primary cause of the peroxidase-mediated lysis of erythrocytes. PMID- 3340622 TI - Temporal response of the fetal pulmonary circulation to pharmacologic vasodilators. AB - To determine the temporal response of the fetal pulmonary circulation to pharmacologic vasodilators and to assess vasoreactivity following vasodilation, we infused either acetylcholine, histamine, or bradykinin directly into the left pulmonary artery of 21 chronically prepared fetal sheep. Blood flow (Q) to the left lung was measured by electromagnetic flow transducer. Left pulmonary artery infusion of acetylcholine at 1.5 micrograms.min-1 for 2 hr produced an increase in Q from 59 +/- 8 ml.min-1 to a peak of 113 +/- 10 ml.min-1 at 20 min into the infusion (P less than 0.001). After the peak at 20 min, Q steadily declined toward baseline to 66 +/- 7 ml.min-1 at the end of the 2-hr infusion period (P less than 0.01). Q in the 1/2-hr period following infusion was significantly less than the baseline period (47 +/- 6; P less than 0.04) with no change in pulmonary artery pressure. Similar patterns were seen with 2-hr infusions of histamine (150 ng.min-1) and bradykinin (100 ng.min-1). After a 2-hr infusion of one of the agents, a repeat infusion with that agent or a different one resulted in a diminished response. We conclude that fetal pulmonary vasodilation in response to local infusion of acetylcholine, histamine, or bradykinin is not sustained over a 2-hr period, and that following 2-hr exposure to vasodilators, pulmonary vascular resistance is increased and pulmonary vasoreactivity to pharmacologic vasodilators is decreased. PMID- 3340623 TI - Teratogenic interaction of ethanol and hyperthermia in mice. AB - Alcohol and maternal hyperthermia have been implicated in human birth defects. Both ethanol and heat can induce neural tube defects (NTDs) and other developmental abnormalities in mice when large doses are given during pregnancy. To explore the teratogenic interaction of both agents, pregnant ICR mice were injected with a single dose of 25% ethanol and/or were heat-stressed in a water bath at 42 degrees C on the morning of Day 8 of gestation. Combined treatment with ethanol (0.01-0.02 ml/g) and heat (10 min), when they were given concurrently or 1 hr apart, resulted in a significant increase of resorptions and externally malformed fetuses. Skeletal malformations and visceral variations also increased significantly following a concurrent exposure to both agents. These results indicate that ethanol and heat can be synergistically teratogenic in mice when the doses of each agent are below the teratogenic threshold. It was also suggested that pretreatment with a small dose of ethanol may not enhance the teratogenicity of heat when the hyperthermic stress is strong enough and teratogenic by itself. PMID- 3340624 TI - Regulation of biliary protein secretion in dogs. AB - The biliary secretion of protein in response to bile acids and other agents known to increase bile flow was examined in a chronic bile fistula dog model. Infusion of 25, 50, or 75 mumole/kg/hr sodium taurocholate after 3 hr of bile fistulization increased biliary protein output significantly by 52, 86, and 108% respectively compared to preinfusion values. A proportionate increase in biliary albumin output during taurocholate choleresis was demonstrated. Protein outputs during bile fistulization without taurocholate replacement were unchanged. The non-micelle-forming bile acid dehydrocholate markedly increased bile flow but did not change protein output. Similarly, the hormonal choleretics glucagon and secretin caused significant decreases in biliary protein concentration but no change in protein output. These data indicate a correlation between biliary protein secretion and bile acid-dependent bile flow. It is likely that regulation of certain proteins is dependent on the micelle-forming properties of bile acids. PMID- 3340625 TI - Potentiated vasoconstrictor response to vasopressin following meclofenamate in conscious rats. AB - Experiments were performed to test the hypothesis that release of vasodilator cyclooxygenase products may attenuate the systemic and renal vasoconstrictor responses to arginine vasopressin (AVP) in the conscious, chronically instrumented rat. Four groups of animals were studied under the following conditions: (i) AVP infused iv at 2 ng/min for 40 min followed by a 15-min postcontrol; (ii) pretreatment with meclofenamate (3 mg/kg iv) followed by AVP infusion; (iii) meclofenamate pretreatment followed by saline vehicle infusion; and (iv) saline vehicle infusion alone (time control). AVP increased mean arterial blood pressure (MABP) in both meclofenamate-treated (n = 12) and untreated (n = 12) animals; however, the pressor response was significantly greater in animals with cyclooxygenase inhibition. Both heart rate (HR) and cardiac output (CO) (n = 6) fell during AVP infusion, but there were no differences between the meclofenamate-treated and the untreated groups. However, the total peripheral resistance response to AVP was significantly greater in animals treated with meclofenamate than the untreated group. Renal blood flow (RBF) was not affected by AVP infusion alone, but RBF fell significantly in animals given AVP after cyclooxygenase inhibition. The renal vascular resistance response to AVP was also enhanced by cyclooxygenase inhibition. There were no changes in any of the hemodynamic variables in either of the control protocols (i.e., meclofenamate alone or vehicle). These data demonstrate a consistent effect of cyclooxygenase inhibition to augment the systemic and renal vasoconstrictor responses to AVP, and suggest that endogenous vasodilator prostaglandins attenuate the potent vasoconstrictor action of this peptide in vivo. PMID- 3340626 TI - Selenium incorporation into selenoproteins in the Se-adequate and Se-deficient rat. AB - To rapidly discriminate between selenoproteins and Se-binding proteins, SDS + 2 mercaptoethanol treatment and then gradient SDS-slab gel electrophoresis was used to remove loosely bound Se from proteins while separating protein subunits according to molecular weight. This technique was used to study the nature and time course of 75Se incorporation into selenoproteins. Male weanling rats were fed either a Se-adequate (0.35 ppm Se) or a Se-deficient (less than 0.02 ppm Se) diet for 20-41 days, injected iv with 50 microCi [75Se]selenite (100 microCi/micrograms Se), and sacrificed 1, 3, 24, or 72 hr after 75Se injection. At 1 and 3 hr, a 55-kDa plasma 75Se protein contained the most 75Se of any 75Se protein observed in any tissue in either Se-adequate or Se-deficient rats. At 24 and 72 hr, a 23-kDa 75Se protein (glutathione peroxidase subunit) in liver cytosol was the second-most labeled 75Se protein observed in Se-adequate rats. The second-most labeled 75Se protein in Se-deficient rats was a 17-kDa 75Se protein in testes at 24 and 72 hr. 75Se proteins of 10, 14, 45, and 65 kDa as well as lesser amounts of other 75Se proteins were also detected. In a separate experiment, cycloheximide pretreatment eliminated 75Se labeling of any of the 75Se proteins, demonstrating that protein synthesis is required for Se incorporation. The rise and fall of various 75Se proteins with time suggests that these seleno-proteins may be important in the flux of Se between tissues. PMID- 3340627 TI - Endothelial cell heterogeneity: antioxidant profiles determine vulnerability to oxidant injury. AB - Human umbilical vein endothelial cells were more sensitive to hydrogen peroxide lysis than cow pulmonary artery endothelial cells. Conversely, activated neutrophils which utilize hydrogen peroxide-mediated cell cytotoxicity cell mechanisms were more toxic to the cow pulmonary artery cells. This discordance was not related to neutrophil adhesion to either cell type or cell passage number. The antioxidant profiles of the endothelial cells revealed that cow pulmonary artery cells were rich in catalase to consume bolus hydrogen peroxide presented to them, while human umbilical vein endothelial cells utilize glutathione peroxidase-linked mechanisms to detoxify a slower more sustained release of hydrogen peroxide generated by neutrophils. Endothelial cells from different species and sites may utilize diversified antioxidant protective mechanisms. PMID- 3340629 TI - Gracile axonal dystrophy (GAD), a new neurological mutant in the mouse. AB - A new neurological mutant has been found in the F2 offspring of CBA/Nga and RFM/Nga mice. Affected mice exhibited ataxia beginning at about 80 days of age, followed by tremor, difficulty in moving, and muscular atrophy of the hind limbs. The neurological signs became progressively severe, and death occurred by 5 to 6 months of age. Since the animals could be distinguished from normal mice by the abnormal positions of the hind limbs when the mouse was hung by the tail after 1 month of age, they could be bred until onset of the signs. Pathological examination revealed neuroaxonal dystrophy and degeneration in the gracile nucleus of the medulla oblongata and the gracile fascicules of the spinal cord, which could be the main cause of the clinical signs. The mutation is inherited as an autosomal recessive trait. It was, therefore, named gracile axonal dystrophy (GAD) with the gene symbol gad. The mice could be a new pathological model for the study of neuroaxonal dystrophy. PMID- 3340628 TI - Bile acid secretion and pool size during phenobarbital induced hypercholeresis. AB - An increase in bile flow after phenobarbital administration occurs in the rat and other species; however, the mechanism(s) of the choleretic effect is incompletely understood and the role of the increase in liver weight is controversial. We therefore measured bile flow, bile acid secretion and pool size in male Sprague Dawley rats pretreated with phenobarbital (75 mg/kg/day) for 6 days; liver weight, liver cell volume and DNA content were also evaluated. Phenobarbital treatment increased liver weight and mean hepatocyte volume by 39 and 26%, respectively, while total DNA content did not change, thus indicating that the hepatomegaly results principally from hypertrophy rather than hyperplasia. Bile flow was significantly higher in treated rats when expressed per unit of body weight (64.6 +/- 2.4 (S.E.) vs 53.3 +/- 1.6 microliter/min/kg; P less than 0.05) but was unchanged when expressed per gram of liver (1.40 +/- 0.04 vs 1.37 +/- 0.06 microliter/min/g; P greater than 0.5). The initial bile acid secretion rate and pool size were both significantly reduced in the phenobarbital group compared to controls (1224.2 +/- 110.4 vs 1656.6 +/- 163.2 nmol/kg/min and 562.8 +/- 41.5 vs 814.3 +/- 78.3 mumol/kg; both P less than 0.05), whereas the basal synthetic rate was unchanged. These findings suggest that the enlarged, phenobarbital treated hepatocyte produces more bile than the normal cell, despite the decreased secretion of bile acids. Therefore, the drug-induced choleresis involves a selective increase in the bile acid-independent fraction of bile flow. PMID- 3340630 TI - Thyroid hormone levels and cigarette smoking in baboons. AB - Using a primate animal model, two studies were undertaken to examine the effects of cigarette smoking on thyroid hormone levels. In study 1, mean total triiodothyronine (total T3) and mean total thyroxine (total T4) levels were measured in two groups of baboons (Papio cynocephalus) who were taught to smoke cigarettes using operant conditioning techniques. The smokers were divided into established and naive smokers according to pack-years of exposure. A control group of never-smoker baboons was included for comparison. Blood sampling was done after long-term cigarette consumption and again 1 week after cigarette deprivation. In the naive smoker group, mean total T3 concentrations were reduced below control group values (P less than 0.05). After cigarette deprivation for 1 week, mean total T3 values returned to normal. No significant differences in total T4 levels were observed in either group. In study 2, we assessed some other indices of thyroid function. The same groups of baboons were divided into good and poor smokers by plasma cotinine and blood carboxyhemoglobin (% COHb) levels during 28 weeks of cigarette smoking activity. Immediate fluctuations and reductions in total T3 levels were observed that were not accompanied by reductions in total T4. The animals were then cigarette deprived for 1 week and blood samples were obtained every other day during this period. Significant increases in total T3 concentrations were observed in poor smokers immediately after cessation. Both groups also exhibited significant reductions (P less than 0.05) in T3 uptake and free T4 index (FT4I) when compared to control group values. These data suggest that poor smokers are more susceptible to thyroid hormone level shifts than more established smokers, since the established smokers become habituated to the compounds contained in cigarette smoke through repeated exposure. PMID- 3340632 TI - A decrease in cysteine levels causes the glutathione deficiency of aging in the mosquito. AB - Our previous results indicated that a glutathione (GSH) deficiency is a determinant of the aging process in many tissues and organisms. Correction of this deficiency in the aging mosquito by feeding the cysteine (Cys) precursor magnesium thiazolidine carboxylic acid (MgTc) suggested that the cause could be a lack of Cys. Adult mosquitoes (Aedes aegypti) were fed either a control diet or a diet supplemented with MgTC and then were analyzed for their Cys, cystine, GSH, and glutathione disulfide contents with our HPLC method. The life span profile of Cys levels paralleled that of GSH in the control group with high levels in the young that decreased during maturity and aging. Cystine and glutathione disulfide were undetectable. The causal relationship between the Cys and the GSH deficiencies was shown in the MgTC-supplemented group with an 83% increase in Cys and a 39% increase in GSH relative to control values. Further the conversion steps of MgTC to Cys and then to GSH were verified by use of buthionine sulfoximine. These results demonstrate that a Cys deficiency occurs in the aging mosquito and is the cause of the GSH deficiency. PMID- 3340633 TI - Recent aspects of diagnosis and treatment of lipoprotein disorders. Impact on prevention of atherosclerotic diseases. Proceedings of an international symposium. Vienna, August 21-23, 1986. PMID- 3340631 TI - Effect of bile anionic polypeptidic fraction on the fate of cholesterol carried by liposomes in the rat. AB - [14C]Cholesterol associated with liposomes with or without anionic polypeptidic fraction was administered intravenously to the rat. The cholesterol originated from liposomes including anionic polypeptidic fraction is secreted in bile much later, is stored in liver in higher quantity, and is metabolized into bile salts in lesser quantity during the 4 hr of experimentation than the cholesterol issued from liposomes exempt of anionic polypeptidic fraction. From these results it can be postulated that the cholesterol associated with liposomes containing anionic polypeptidic fraction might be directed in a particular liver pathway. PMID- 3340634 TI - Serum lipid levels in elementary and junior high schoolchildren and their relationship to obesity--Shinjo-cho study. PMID- 3340635 TI - Lipids and lipoproteins during pregnancy. PMID- 3340636 TI - Hematoporphyrin retention by atherosclerotic plaques in the broad breasted white turkey: studies on the distribution and quantitation in aortic tissue and on the uptake by cultured aortic smooth muscle cells. PMID- 3340637 TI - Imaging of human atherosclerotic lesions by 123-I-low-density lipoproteins (LDL). PMID- 3340638 TI - Management of hyperlipoproteinemia--clinical aspects. PMID- 3340639 TI - Dietary treatment of hypercholesterolemia in children: recent aspects. PMID- 3340640 TI - Effect of two hypocaloric diets on HDL-cholesterol and fatty acid composition in grossly obese adolescents. PMID- 3340641 TI - Drug therapy in children and adolescents with familial hypercholesterolemia. PMID- 3340642 TI - Lovastatin alone and in combination for treatment of primary hypercholesterolemia. PMID- 3340643 TI - Regression of atherosclerosis in patients with familial hypercholesterolaemia under LDL-apheresis. PMID- 3340644 TI - Plasma exchange in type II hypercholesterolemia. PMID- 3340646 TI - Intralipid disappearance from the circulation in critically ill patients. PMID- 3340645 TI - Evaluation of selective LDL-removal in the treatment of familial hypercholesterolemia: double membrane filtration and adsorption system. PMID- 3340647 TI - The ratio of HDL to total cholesterol: long-term prognosis in men with and without coronary heart disease and in different ages, ethnic origins and serum cholesterol categories. PMID- 3340648 TI - Atherosclerosis precursors in Finnish children and adolescents--serum lipids, tracking of serum lipids, and preliminary results from cluster analyses of risk factors. PMID- 3340649 TI - Pediatric hyperlipoproteinemia: the phenotypic expression of hyperapobetalipoproteinemia in young probands and their parents. AB - These data on families of pediatric probands with the hyperapoB phenotype confirm and extend our previous findings of familial aggregation of hyperapoB and document further the expression of hyperapoB in the pediatric age group (Sniderman et al, 1985). In agreement with a more recent report (Beaty et al, 1986) the data suggest, but do not prove, the presence of a Mendelian dominant trait for hyperapoB. The observation that most of the parents affected with hyperapoB were normolipidemic clearly suggests a difference between the expression of hyperapoB in these families and FCH. Further studies on the basic biochemical and genetic defect(s) underlying these common disorders associated with CHD will be necessary to provide a better understanding of the pathogenesis of these important lipoprotein disorders. A significant proportion of children referred to a Lipid Clinic for suspected hyperlipidemia or because of a family history of premature CHD may have hyperapoB. We suggest that measurement of plasma LDL B be added to the standard measurements of lipids and lipoproteins made in Lipid Clinics and that further studies be performed on the utility of using the ratio of LDL C/B as a useful clinical tool to differentiate between those patients with hyperapoB and those with more conventional type II hyperlipoproteinemia. PMID- 3340650 TI - Regional cerebral glucose utilization during vasopressin-induced barrel rotations or bicuculline-induced seizures in rats. AB - Regional cerebral metabolic rates of glucose (rCMRglu) were measured in conscious rats grouped according to three treatments: control, bicuculline (5.5 mg/kg s.c.), and intracerebroventricular arginine vasopressin (0.5 micrograms/5 microliter). Rats in the latter group were pre-exposed to the peptide 48 h earlier to render them 100% susceptible to a motor output termed barrel rotation (BR). Marked increases in rCMRglu occurred in all brain areas investigated after bicuculline. Increases after intracerebroventricular arginine vasopressin were smaller and occurred in fewer brain areas. Opposite to bicuculline, arginine vasopressin reduced rCMRglu in hippocampus and auditory cortex. The data confirm marked stimulation of rCMRglu during bicuculline-induced seizures and provide initial data for an endogenous peptide that causes BR. Generalized seizures and BR may share some neural substrates, but they produce distinct changes in rCMRglu. The rCMRglu changes are compatible with the interpretation that BR is initiated by brainstem/cerebellar areas that process visual-vestibular information, with subsequent involvement of higher brain structures. PMID- 3340652 TI - Locomotor hyperactivity in hypertensive rats. AB - In the presented studies, both the spontaneous motor activity and the locomotor responses to amphetamine challenge were assessed in normotensive rats and in hypertensive rats. As compared to their appropriate controls, both experimentally (either renal or deoxycorticosterone salt) hypertensive rats and spontaneously hypertensive rats maintained a higher level of spontaneous motor activity. In addition, intraperitoneal administration of amphetamine produced stimulation of forward locomotion, and head and body rearing (as shown by an increase in gross movements) and increased grooming and sniffing (as shown by an increase in fine movements). It was also found that either experimentally or spontaneously hypertensive rats displayed a greater degree of locomotor stimulant responses to amphetamine administration as compared to their appropriate controls. The results indicate that the mechanisms underlying the pathogenesis of hypertension may be related to the development of locomotor hyperactivity in rats. PMID- 3340651 TI - Antiarrhythmic properties of antidepressant drugs after coronary artery occlusion and reperfusion in rats. AB - The effects of the intravenously administered antidepressant drugs mianserin, imipramine, metapramine, nomifensine and amineptine against ischaemia and reperfusion arrhythmias were investigated in anaesthetized rats. Imipramine, metapramine, mianserin and high doses of nomifensine (0.5 mg.kg-1) reduced the mortality and the duration of ventricular fibrillation observed following coronary artery ligation. Amineptine was ineffective in preventing early postligation arrhythmias. With the tricyclic antidepressant drugs imipramine and metapramine, the arrhythmias were practically suppressed after 15 min following coronary artery ligation. The incidence of reperfusion arrhythmias was significantly reduced by tricyclic antidepressant drugs. In contrast, amineptine was not effective and did not alter cardiac function. It was suggested that nonspecific effects of these drugs account for their antiarrhythmic action. The most plausible explanation for their antiarrhythmic action may be a quinidine like cardiac depressant activity. PMID- 3340653 TI - Red lacrimal secretion (chromodacryorrhea) induced by cholinergic drugs in rats subjected to the watertank technique. AB - Red tears (chromodacryorrhea) in rats are due to porphyrin pigments secreted by Harder's glands and are believed to involve muscarinic mechanisms. Chromodacryorrhea was observed in rats treated with pilocarpine, oxotremorine and neostigmine and this response was blocked by anticholinergic drugs. However, in rats deprived of rapid eye movement (REM) sleep (REMd) for 3 days, through the watertank technique, chromodacryorrhea did not develop even when cholinergic agonists were given in doses severalfold higher than those active in non-REMd animals. Decrease of chromodacryorrhea also was obtained in rats previously treated with neostigmine; conversely, previous treatment with atropine induced an increased chromodacryorrhea when the rats were further challenged with pilocarpine and oxotremorine. It is proposed that the absence of red tears in REMd rats might be due to a down regulation of peripheral cholinergic receptors. PMID- 3340654 TI - Differential effects of verapamil on various gastric lesions in rats. AB - Verapamil (3, 10, 20 mg/kg-1) increases the necrotizing effects of oral 25% NaCl or 100% ethanol. Damage by 0.6 N HCl was not equally affected since 1 mg/kg-1 of verapamil decreased the ulcer index whereas the higher doses augmented it. Pharmacologically induced gastric lesions were also differently affected by verapamil, ulcers produced by histamine being greatly enhanced and those of reserpine inhibited. Neither indomethacin nor compound 48/80 ulcers were modified. These results suggest that verapamil modifies the susceptibility of the gastric mucosa to damage. PMID- 3340655 TI - Rising from a supine position to erect stance. Description of adult movement and a developmental hypothesis. AB - Standing up from a supine position is important for physical independence. This study was designed to describe movements within specific body regions used to stand up from a supine position. Another purpose was to identify motor developmental sequences for the upper extremities, lower extremities, and axial region for this rising task. Thirty-two young adults were videotaped while rising from a supine position 10 times. Descriptive categories were formed to portray movements of the upper extremities, lower extremities, and axial region. Subjects varied greatly in the movement patterns they used to rise. Only 25% of the subjects demonstrated a similar combination of movements during rising. That combination involved symmetrical use of the limbs and trunk while flexing forward from a supine position, moving through sitting to squatting, then standing. An ordering of categories was found for each body region that was proposed as a developmental sequence of movement patterns for this task. The variability of subjects' movements while rising provides clinicians with numerous movement combinations that might be used when teaching patients to stand from a supine position. PMID- 3340656 TI - Make tests and break tests of elbow flexor muscle strength. AB - The purposes of this investigation were 1) to compare the forces produced by the elbow flexor muscles during make tests and break tests and 2) to determine the reliability of each of the test procedures. I used a hand-held dynamometer to perform two make tests and two break tests on 27 young women. The forces produced by the elbow flexor muscles during break tests were significantly larger than (p less than .001), albeit correlated with (r greater than .80), the forces produced during make tests. Each testing procedure was reliable (r = .909 for make tests; r = .922 for break tests). On the basis of reliability, one type of testing cannot be considered clearly superior to the other. PMID- 3340657 TI - Angina and ST-segment depression during treadmill and arm ergometer testing in patients with coronary artery disease. AB - The clinical use of exercise rehabilitation programs has increased for patients with coronary artery disease. Exercise testing in these programs typically is conducted on a treadmill or cycle ergometer, although many patients' vocations require upper extremity activities and some patients cannot perform lower extremity exercises. To compare the hemodynamic responses and the incidence of angina and ST-segment depression during upper and lower extremity exercise in patients with coronary artery disease, we administered symptom-limited arm ergometer and submaximal or maximal symptom-limited treadmill tests to 95 cardiac rehabilitation patients who had completed an eight-week exercise training program. Treadmill testing resulted in significantly higher heart rates, systolic blood pressures, and double products than arm ergometer testing. The incidence of ST-segment depression was significantly greater with treadmill testing than with arm ergometer testing, but the incidence of angina was not different between tests. Ten patients had ST-segment depression during both arm ergometer and treadmill testing, and the double products at the onset of ST-segment depression were not different. Our data suggest that arm ergometer testing is less likely to result in ST-segment depression than treadmill testing in patients with coronary artery disease, possibly because of the lower hemodynamic responses during arm ergometer testing. PMID- 3340658 TI - Effects of heavy-resistance triceps surae muscle training on strength and muscularity of men and women. AB - The purpose of this study was to determine selected functional and structural effects of heavy-resistance training on the triceps surae muscles of men and women. We pretested 28 men and 28 women for triceps surae muscle isotonic strength and muscularity after five practice sessions that familiarized them with the study equipment. Triceps surae muscle isotonic strength was determined using a 1-repetition maximum seated heel raise. Muscularity involved the measurement of relaxed lower leg circumference and net circumference and ultrasonically determined triceps surae muscle thickness. Twenty-eight subjects (14 men, 14 women) were selected randomly after pretesting to participate in 24 sessions of standardized weight training primarily involving the triceps surae muscles, and the remaining subjects (14 men, 14 women) served as nontraining controls. After eight weeks of training, triceps surae muscle isotonic strength had increased significantly (p less than .001) for both men and women in the Treatment Group when compared with the Control Group. No other dependent variables changed significantly. We concluded that eight weeks of heavy-resistance training involving the triceps surae muscles elicits similar significant increases in isotonic muscle strength in both men and women without concurrent increases in muscularity. PMID- 3340659 TI - Comparison of the reliability of the Orthoranger and the standard goniometer for assessing active lower extremity range of motion. AB - The purpose of this study were to determine 1) the reliability of the Orthoranger for assessing active lower extremity joint range of motion, 2) specific methods for applying the Orthoranger, and 3) whether a correlation exists between the measurements obtained with the Orthoranger and those obtained with a standard goniometer. Ten men and 10 women, mean ages 28.3 +/- 5.1 and 30.0 +/- 10.1 years, respectively, participated in the study. Random selection was used to determine testing sequences. The Orthoranger and the goniometer were used to measure each joint three times during the five sessions. Results indicated that both instruments were reliable for assessing active lower extremity joint ROM. The goniometer showed greater intraclass correlations and confidence levels for all movements except hip lateral rotation, which demonstrated a higher intraclass correlation for the Orthoranger. In addition, all motions except hip adduction and knee extension demonstrated a positive relationship between instruments. Compared with a manual goniometer, the added costs for purchase and use of the Orthoranger appear to be unnecessary until such time that factors enhancing its inherent reliability are identified. PMID- 3340660 TI - Effect of stabilization on maximal isokinetic torque of the quadriceps femoris muscle during concentric and eccentric contractions. AB - The purpose of this study was to investigate the effect of stabilization on the maximal isokinetic torque generated by the quadriceps femoris muscle during concentric and eccentric contractions at different velocities using the KIN/COM isokinetic dynamometer. Fifteen female volunteers between the ages of 18 and 32 years were trained to perform maximal isokinetic concentric and eccentric contractions. Each subject participated in two testing sessions. In one testing session, subjects were stabilized maximally, and in the other testing session, subjects were stabilized minimally. Subjects were tested both concentrically and eccentrically at velocities of 30 degrees, 60 degrees, 90 degrees, 120 degrees, 150 degrees, 180 degrees, and 200 degrees/sec. The velocity sequence and stabilization procedure used were randomly assigned. Two nested model analyses of variance followed by post hoc comparisons were used to analyze the data. Results revealed no significant difference between the maximal stabilization procedure and the minimal stabilization procedure for concentric and eccentric contractions. The results of this study should aid rehabilitation specialists in the development of testing and rehabilitation procedures when using the KIN/COM. PMID- 3340661 TI - Effect of helium-neon laser irradiation on peripheral sensory nerve latency. AB - The purpose of this randomized, double-blind study was to determine the effect of a helium-neon (He-Ne) laser on latency of peripheral sensory nerve. Forty healthy subjects with no history of right upper extremity pathological conditions were assigned to either a Laser or a Placebo Group. Six 1-cm2 blocks along a 12-cm segment of the subjects' right superficial radial nerve received 20-second applications of either the He-Ne laser or a placebo. We assessed differences between pretest and posttest latencies with t tests for correlated and independent samples. The Laser Group showed a statistically significant increase in latency that corresponded to a decrease in sensory nerve conduction velocity. Short-duration He-Ne laser application significantly increased the distal latency of the superficial radial nerve. This finding provides information about the mechanism of the reported pain-relieving effect of the He-Ne laser. PMID- 3340662 TI - Trochanteric girdle to prevent hip dislocation in standing. Suggestion from the field. PMID- 3340663 TI - Bobath axillary support for adults with hemiplegia. A biomechanical analysis. AB - The purpose of this article is to report on a simple biomechanical analysis of the effects of an axillary support on shoulder subluxation. The underlying postulate was that an axillary support always is accompanied by an increase in shoulder abduction. The immediate effect of axillary support, as confirmed by roentgenograms, was a partial reduction of inferior subluxation and a decrease in the magnitude of the vertical component of the internal resultant force on the shoulder. After the axillary support was applied, the total force acting on the shoulder tissues increased with the abduction angle. The results of this study indicate that the axillary roll size and position and the stabilizing strap tension should be adjusted to the patient's specific problem or problems. This article provides a simple method to estimate, in a given patient, the magnitude and the direction of the forces involved in axillary support. PMID- 3340664 TI - Predictors of academic and clinical performance in a baccalaureate physical therapy program. AB - The purpose of this retrospective study was to determine the best predictors of academic and clinical performance in a physical therapy undergraduate program. The records of 42 graduates of the program were reviewed to obtain data concerning 1) preadmission cumulative grade point averages (GPAs), 2) written composition scores, 3) interview ratings (INTVs), 4) preprofessional faculty ratings, 5) mean Allied Health Professions Admission Test (MAHPAT) scores, and 6) scores on the comprehensive examination administered at the end of the educational program. The results of the comprehensive written and oral-practical examination were used as a measure of the students' academic achievement and clinical performance. Multiple regression analyses revealed that both academic achievement and clinical performance can be predicted reliably (p less than .001) from the preadmission requirements. The two viable predictors of academic achievement were GPA and MAHPAT. The GPA and MAHPAT accounted for 30.5% and 8.0%, respectively, of the total variance (40.6%) in academic achievement. The INTV and GPA were the two viable predictors of clinical performance. They accounted for 34.6% and 7.5%, respectively, of the total variance (44.8%) in clinical performance. PMID- 3340665 TI - Functional assessment using the microcomputer. PMID- 3340666 TI - Computer-designed prostheses for orbitocranial reconstruction. AB - Three-dimensional imaging is an adjunct to preoperative evaluation and surgical management in some patients with complex anatomic defects of various etiologies. Deformities defined by conventional computerized tomography can be viewed as accurate three-dimensional images calculated from the original scan. The images are viewed on a high-resolution video monitor and can be photographed for a permanent record. A computer-controlled milling device can use these data to fabricate prostheses. The prostheses aid reconstructive surgery through use as an alloplastic implant, as a template to fashion autogenous bone grafts, or as a model for tissue removal. We have utilized three-dimensional imaging in combination with computer-assisted prosthesis manufacture in six patients with complex orbitocranial deformities. Four patients have undergone reconstructive surgery with satisfactory results and no complications thus far. The use of computer-designed prostheses adds a new aspect to orbitocranial reconstructive surgery that facilitates increased accuracy in the correction of anatomic defects. PMID- 3340667 TI - Cephalometric and anthropomorphic observations of Binder's syndrome: a study of 19 patients. AB - Binder's syndrome (maxillonasal dysplasia) is a disorder characterized by nasomaxillary hypoplasia. To ascertain the extent of underdevelopment of the midfacial skeleton and soft tissues, 19 of 29 patients with Binder's syndrome were retrospectively evaluated, both with cephalometry and anthropometry. Ten females and nine males were placed collectively into three age groups: 6 years, 10 years, and 16 to 17 years. Cephalometric measurements disclosed a short anterior cranial base (S-N), a normal length of the vertical maxilla (SE-PNS), a decreased horizontal maxilla (PNS-A, Co-A), a recessed orbitale (SNO), and a high normal mandibular length (Co-Gn). Anthropometry revealed a large nasofrontal angle, acute nasal inclination and nasolabial angle, decreased nasal prominence (Sn-Prn), a decreased columellar length (C-Sn), and a normal vertical nose (N-Sn) and upper lip (Sn-Sto) length. PMID- 3340668 TI - Manofluorography of deglutition after total laryngopharyngectomy. AB - Manofluorography is a new technique for the evaluation of swallowing that provides simultaneous display of manometry and videofluoroscopy on one video screen. Data are presented from a study of deglutition in 10 patients who had prior total laryngopharyngectomy with replacement by either jejunal graft or gastric pull-up. Factors that enhance bolus passage are the presence of a widely patent graft and an intact swallowing reflex. Factors that impair bolus transit include stricture, jejunal peristalsis, impaired lingual coordination, and stenosis at the anastomotic site. The swallowing patterns of these patients serve as models of the open and closed cavity swallow and illustrate principles of manofluorographic interpretation. PMID- 3340669 TI - The use of free flaps in burn patients: experiences with 70 flaps in 65 patients. AB - A series of 70 microvascular free flaps employed in 65 burn patients is presented. The total survival incidence of the flaps was 87 percent. Satisfactory wound healing was achieved in 80 percent of a total of 54 flaps in fresh burn patients. In the 16 patients with healed burns, flap survival was 100 percent with satisfactory functional and cosmetic results. The cruxes of dealing with difficult fourth-degree burns by using microvascular free flaps and our special considerations about the indications and overall morbidities of the donor site are discussed. This large-series report confirms other occasional reports on the use of free flaps in burn patients. It is our belief that the microvascular free flap is the most expeditious means of dealing with refractory burn wounds, even when more conventional techniques are available. In certain cases, the microvascular procedure is the only method that can salvage an extremity. PMID- 3340670 TI - Vascular anatomy of the upper extremity muscles. AB - This study delineates the vascular anatomy of the upper extremity with particular attention toward the size, location, and number of vascular pedicles supplying each muscle. Ten cadaver upper extremities were dissected. A total of 440 muscles and 2209 pedicles were identified. The major "named" arterial source, number of pedicles, and pattern of perfusion for each muscle were delineated. Detailed description of the vascular anatomy of muscles commonly used for tendon transfer and local flaps is presented. The potential use of the coracobrachialis flap for contouring the infraclavicular area is elucidated. The anatomic bases of the anconeus and flexor carpi ulnaris flaps are confirmed. The radial and ulnar arteries may be used as microvascular donor or recipient vessels without compromising forearm muscle perfusion. PMID- 3340671 TI - Simultaneous multiple toe transfers in hand reconstruction. AB - Our experience with simultaneous transfer of two or more toe units to the same hand where multiple digits were missing is presented. Forty-six toes from 38 feet were transferred to reconstruct 19 hands in 19 patients. The transfers consisted of 7 combined second and third toe units and 32 single toes. Three patients had a primary and 16 patients had a secondary reconstruction. There was one complete and one partial failure. The two-point discrimination ranged from 6 mm to protective sensation. Total active movement averaged 57 degrees in the thumb and 127, 93, 71, and 68 degrees, respectively, in the fingers reconstructed at middle phalanx, proximal phalanx, metacarpophalangeal joint, and metacarpal head. Pulp to-pulp pinch averaged 2.4 kg in patients who had thumbs reconstructed and averaged 3.0 kg in patients who had normal thumbs. There was no cold intolerance, and no significantly disabled foot occurred except one with scissoring deformity. Simultaneous multiple toe transfer in hand reconstruction is feasible without increased complications both in primary and secondary wound conditions. It is time-effective and cost-effective. PMID- 3340672 TI - The "double barrel" free vascularized fibular bone graft. AB - A further modification of the free vascularized fibular bone graft is described in which a transverse osteotomy is made from the anterolateral aspect of the fibular shaft just distal to the entry of the nutrient artery. This produces two vascularized bone struts that may be folded parallel to each other but that remain connected by the periosteum and muscle cuff surrounding the peroneal artery and vein. The proximal strut is vascularized by both a periosteal and an endosteal blood supply, whereas the distal strut is vascularized by a periosteal blood supply alone. This so-called "double barrel" free vascularized fibular graft has been employed in three patients with segmental bone defects of the distal femur and in one patient with adjacent bony defects of the radius and ulna. PMID- 3340673 TI - Comparative evaluation of aloe vera in the management of burn wounds in guinea pigs. AB - An experimental study was designed using Hartley guinea pigs, who received full thickness burns covering 3 percent of their body surface area by direct contact with a hot plate. A total of 40 animals were equally divided among four modalities of closed burn wound management as follows: group I: silver sulfadiazine (Silvadine); group II: aloe vera gel extract (Carrington Dermal Wound Gel); group III: salicylic acid cream (aspirin); and group IV: plain gauze occlusive dressing only. The dressings were changed daily, and the size and appearance of each burn wound were recorded until complete healing. On the sixth postburn day, quantitative burn wound cultures were made. The average time to complete healing in the control group was 50 days, and the only significant difference was found in the aloe vera-treated animals, which healed on an average of 30 days (p less than 0.02). Wound bacterial counts were effectively decreased by silver sulfadiazine (p = 0.015) and by aloe vera extract (p = 0.015). From our data it appears that aloe gel extracts permit a faster healing of burn wounds. PMID- 3340674 TI - Dermal and epidermal response to soft-tissue expansion in the pig. AB - To evaluate the dermal and epidermal response to soft-tissue expansion in the pig, round tissue expanders were placed dorsally under tattooed patterns and inflated over 6 weeks. Surface area, skin thickness, histologic changes, and collagen content were evaluated at 6-week intervals. Epidermal thickening and dermal thinning were observed. Dermal thinning persisted 36 weeks after expansion. Dermal collagen content was decreased, although collagen density remained unchanged. Total collagen content calculated within an expanded square grid increased. These data support a theoretical gain in the dermal layer as well as epidermal layer in response to tissue expansion. PMID- 3340675 TI - The tensiometric properties of expanded guinea pig skin. AB - Our purpose in this study was to evaluate the tensile properties of expanded skin. In five guinea pigs, 29-cc ovoid tissue expanders were placed and sequentially expanded every 4 days until maximum volume was achieved. Five control and five expanded skins were harvested. Using an Instron tensile testing apparatus, skins were evaluated for stress-strain, maximum stiffness, and tensile strength, and the results were statistically compared. Centrally located expanded specimens demonstrated significantly weaker stress-strain values: 9.51 in.lb/in3 for expanded versus 30.11 in.lb/in3 for control (p less than 0.001). Maximum stiffness was similarly reduced: 4.56 lb/mm2 for expanded vs. 12.98 lb/mm2 for control (p less than 0.001). This is a 67.4 and 64.9 percent reduction, respectively, for the stress-strain and maximum stiffness. No statistically significant difference was seen in peripherally located expanded specimens relative to the controls: stress-strain expanded, 28.7 in.lb/in3 (p greater than 0.5); maximum stiffness expanded, 12.84 lb/mm2 (p greater than 0.5). Expanded skin demonstrated an average 35 percent reduction in tensile strength. We conclude that the tensile properties of expanded skin are significantly less than unexpanded skin and are a function of the degree of expansion. PMID- 3340676 TI - Anastomosis of vessels of unequal diameter using an interpositional vein graft. AB - In this study, 100 rabbits were used to assess the efficacy of five different methods of microvascular anastomosis where a vessel diameter discrepancy of 5:1 existed. The inferior vena cava of the rabbit was used as a graft in the femoral artery. In 50 percent of the rabbits the graft was reversed to assess the effects on flow. When explored between 7 and 10 days after anastomosis, an overall patency rate of 96 percent was recorded. Three grafts were not patent in the reversed group and one was not patent in the nonreversed group. There was no significant statistical difference in patency rates between any of the groups, as calculated by the Fisher's exact probability test. The tapered end-to-end and side-to-end anastomoses were found to be the most rapid and simplest methods to perform. PMID- 3340677 TI - Graduate medical education and the evaluation of physician competence: the need for radical surgery. PMID- 3340678 TI - Reconstruction of the maxilla with a double musculoperiosteal flap in connection with a composite calvarial bone graft. AB - A new technique is shown for a one-stage reconstruction of the mucosa of the floors of the nose and maxillary sinus, the bone structures of the maxilla and the hard palate, as well as the mucosal layers of the hard and soft palates and vestibulum. To accomplish this coverage, a vascularized calvarial bone graft with temporal muscle from one side is combined with a vascularized temporal muscle flap from the other side to achieve a three-layer "sandwich" plasty. The advantage of this procedure is reconstruction of the complete maxillary defect with the possibility of denture rehabilitation and the avoidance of oronasal fenestration. Besides the possible complication of insufficient vascularization of the bone and muscle grafts, the donor defect in the calvarial bone and the missing muscle for mastication are to be considered. PMID- 3340679 TI - Anterior shoulder reconstruction with pectoralis minor muscle flap. AB - The pectoralis minor flap can be utilized by the reconstructive surgeon to cover defects of the shoulder, chest, and anterior neck without the morbidity or cosmetic deformity associated with the pectoralis major or latissimus dorsi flap. PMID- 3340680 TI - Delayed primary reconstruction of subtotal nail bed loss using a split-thickness nail bed graft on decorticated bone. AB - Split-thickness nail bed grafting is the accepted method of treatment for injuries involving loss of nail bed tissue. The nail bed of the great toe may be used without donor-site morbidity, and nail bed grafting may be combined with other procedures for fingertip reconstruction. A case of fingertip avulsion injury with loss of the nail plate, nail bed, and periosteum over the exposed distal phalanx of the thumb was reconstructed by a split-thickness nail bed graft placed directly on granulating decorticated bone. The length, appearance, and function of the injured dominant thumb were preserved. PMID- 3340682 TI - Nipple-areola reconstruction using intradermal tattoo. AB - A technique of nipple-areola reconstruction with intradermal tattoo is presented. By using various colors, it is possible to tattoo a nipple-areola complex onto the breast that will have an illusion of projection. This technique alone is acceptable to older patients. In younger patients, or in those in whom nipple projection is desired, a simple technique of using a subcutaneously based nipple pedicle is found to be highly effective. PMID- 3340681 TI - A twin tissue expander used in the elimination of alopecia. AB - The tissue expansion system developed at Odstock Hospital in 1983 and subsequently used in clinical practice is described. The case report illustrates the use of the twin version of this device in the elimination of male pattern baldness. Data are given revealing the tissue compliance and growth response to hydraulic expansion. PMID- 3340684 TI - Staff surgery--the inevitable question. AB - The results of a survey of 450 plastic surgeons regarding the practice of operating on their staff members is presented. An overwhelming majority (85 percent) of responding surgeons do operate on their staff. Whether surgery is a "right" of employment or a "reward" for service was addressed. Seventy-two percent felt surgery was a "reward," while only 8 percent felt it was a "right." The results found complications to be relatively minor but numerous (23.5 percent). The need for an office policy is stressed to help eliminate misunderstandings with other employees, and a model office policy is presented and endorsed. PMID- 3340683 TI - The reverse latissimus dorsi muscle flap for closure of meningomyelocele. AB - Closure of the meningomyelocele wound requires stable coverage of the dural repair. In the case presented, multiple conventional attempts at reconstruction failed. A modification of the "reverse" latissimus dorsi flap is presented that successfully managed this low lumbar defect. PMID- 3340685 TI - Dermabrasion for giant nevi. PMID- 3340686 TI - Coverage of lower leg defects. PMID- 3340687 TI - Scleral show. PMID- 3340688 TI - Hibiclens and eye damage. PMID- 3340689 TI - Removing the difficult intradermal suture. PMID- 3340690 TI - Sliding genioplasty under local as an outpatient procedure. PMID- 3340691 TI - Instrument for subpectoral breast augmentation. PMID- 3340693 TI - The computer video image vs. a thirty-five-cent ballpoint pen. PMID- 3340692 TI - Surgical marker. PMID- 3340694 TI - Mini-abdominoplasty. PMID- 3340695 TI - Exercise-induced bronchospasm caused by maprotiline. PMID- 3340696 TI - Acute psychosis in a patient with cerebral cysticercosis. PMID- 3340697 TI - Depression and the Wolff-Parkinson-White syndrome. PMID- 3340698 TI - Pseudostatus epilepticus. PMID- 3340699 TI - Neuroleptic malignant syndrome in pregnancy. PMID- 3340700 TI - Unintentional cuing of responses in a globally aphasic patient. PMID- 3340702 TI - Treatment-responsive depression and hyperparathyroidism. PMID- 3340701 TI - The fear of choking: three successfully treated cases. PMID- 3340703 TI - Polysomnography as an objective diagnostic tool for PTSD. PMID- 3340704 TI - Competency issues in referrals. PMID- 3340705 TI - A case of secondary mania. PMID- 3340706 TI - Clarity of requests for psychiatric consultations. PMID- 3340707 TI - Mortality in schizophrenia--the Iowa Record-Linkage Study: a comparison with general population mortality. PMID- 3340708 TI - Alcoholism and aging in the general hospital. PMID- 3340709 TI - Physical symptoms and self-image in a group of normal adolescents. PMID- 3340710 TI - Chewing and spitting out food as a clinical feature of bulimia. PMID- 3340711 TI - Primary care physicians' perceptions of psychiatric disorders and treatment approaches in young and middle-aged adult patients. PMID- 3340712 TI - Psychiatric consultation for the medically ill elderly in the general hospital: need for a collaborative model of care. PMID- 3340713 TI - Reassessment of gamma doses from the atomic bombs in Hiroshima and Nagasaki. AB - Reassessment of gamma doses from the atomic bombs in Hiroshima and Nagasaki has been carried out with thermoluminescent measurements of ceramic materials, such as bricks and decorative tiles, which were collected from buildings that remain as they were at the time of the explosions. The thermoluminescent measurements were performed using thermoluminescent dating techniques generally used in archaeology. Annual background dose rates from natural radionuclides in the ceramic materials and from environmental radiation including cosmic rays were determined with commercially available thermoluminescent detectors. A time-zero point at the original firing of the ceramic materials was estimated from the age of the buildings given in "the register book." Total background dose was evaluated by multiplying the period between the time-zero point and the time of measurement by the annual dose rate. The resultant gamma doses in Hiroshima and Nagasaki are given as a function of distance from ground zero and are compared with the DS86 (Dosimetry System 1986) and the T65D (Tentative 1965 Dose) gamma doses. PMID- 3340714 TI - The effect of oxygen on the delay in the initiation of DNA synthesis after irradiation. AB - The effect of oxygen on cell cycle delay by low doses of radiation on synchronized Harding Passey melanoma cells has been studied. Cells were irradiated 5 h after subculturing into fresh medium, and the delay before the start of S was measured. DNA synthesis was measured by frequent pulse labeling of the cells with radioactive thymidine to obtain the S-phase profile. The amount by which the irradiated cells S-phase profile had to be moved in time so that both the ascending and descending portions of the first S phase overlayed that of the controls was used as a measure of the delay. The magnitude of the delay was exponentially related to radiation dose and the effect of irradiating in the absence of oxygen was a dose multiplying factor of 2.5. This was similar to the oxygen effect on survival for cells irradiated under the same conditions. PMID- 3340715 TI - Protective effect of corticosteroids on radiation pneumonitis in mice. AB - We explored the protective effect of corticosteroids on the mortality of mice that received thoracic irradiation. Methylprednisolone, 100 mg/kg/week, given from 11 weeks after gamma irradiation of the thorax resulted in an increase in the LD50 (11-26 weeks) from 14.3 +/- 0.3 (mean +/- SE) Gy to 17.6 +/- 0.4 Gy, P less than 0.001, a protection factor of 1.2. Withdrawal of steroids at various times during the period of radiation pneumonitis resulted in accelerated mortality in the next 2-4 weeks, so that the cumulative mortality "caught up" with that of control animals by 4 weeks after steroid withdrawal. However, after the end of the usual period of pneumonitis withdrawal of steroids did not result in accelerated mortality, suggesting that the time when steroids are protective corresponds to the duration of pneumonitis. A smaller dose of steroids, 25 mg/kg/week, was found to be as protective as the larger dose used in the above experiments. The possibility that corticosteroids reduce mortality, even when given many weeks after radiation, may have important practical and theoretical implications. PMID- 3340716 TI - Radiation-induced cardiomyopathy in the dog. AB - Sequential necropsies and histologic evaluations of young adult beagle dogs were performed after irradiation of the thorax. Total doses to the heart were 36, 44, or 52 Gy given in 4-Gy fractions in 4 weeks. One month after irradiation there was little histologic evidence of damage visible by light microscopy. However, ventricular and septal weights were increased, probably due to edema. At 3 months damage to endothelial and mesothelial cells was evident. By 12 months the myocardium was thinned and focal degeneration and loss of muscle cells and Purkinje fibers were observed. There was extensive subendocardial and epicardial fibrosis as well as intimal proliferation in coronary arteries. Morphometric analyses were performed on the myocardium, pericardium, atria, and aorta. There was a slight increase in perivascular connective tissue in the myocardium. The pericardium was increased in thickness and the ratio of smooth muscle to elastin was decreased in the aorta. Severe fibrosis occurred only in the right atrium. At 1 year there was no clinical evidence of heart failure; however, evidence of myocardial damage was present histologically and functionally. Additional stress and continued aging are likely to enhance the damage and lead to serious complications. The interactions of irradiated lung and heart require further investigation. PMID- 3340717 TI - 2-[(Aminopropyl)amino] ethanethiol-mediated reductions in 60Co gamma-ray and fission-spectrum neutron-induced chromosome damage in V79 cells. AB - The radioprotector 2-[aminopropyl)amino] ethanethiol (WR1065), which has been reported to reduce the cytotoxic and mutagenic effects of low LET radiation, was investigated for its ability to protect against low LET (60Co gamma ray) and high LET (fission-spectrum neutron)-induced chromosome damage in V79 cells. Cells were irradiated in G2 phase in the presence or absence of 4 mM WR1065 and were harvested and analyzed 2 h later for chromatid-type aberrations. Irradiation of G2-phase V79 cells in the presence of WR1065 resulted in a 30 to 50% reduction in the frequency of gamma-ray and neutron-induced chromatid-type breaks and exchanges. The effects were found only after exposures of greater than 200 cGy gamma-ray or 50 cGy neutron irradiation. The radioprotector was effective at reducing neutron-induced aberrations after exposures at dose rates of both 10 and 43 cGy/min. Thus the radioprotector WR1065 is an effective anti-clastogenic agent in V79 cells, protecting against both 60Co gamma-ray and fission-spectrum neutron induced aberrations, when present during irradiation. PMID- 3340718 TI - On the application of microdosimetry to radiobiology. AB - The pertinence of proportional counter microdosimetry to radiobiology rests on the idea of the site model; in view of the current emphasis on formalisms based on the distance model, it would appear that the role of experimental microdosimetry as a predictive tool is compromised. In this paper we challenge this opinion. It is shown that, to the extent that the site model is not only limited to convex sites of simple geometry, (a) the site model and the distance model become only complementary aspects (i.e., two possible interpretations) of the same formalism, and current biophysical theory is not equipped to discriminate, based on experimental evidence, between the two; (b) proportional counter microdosimetry retains its validity; and (c) for any cellular system [characterized by a function gamma(chi)] the ratio alpha/beta between the linear and quadratic components of the dose-response function can be calculated as a weighted sum of dose-averaged specific energies measured in a series of spherical sites (of different dimensions). An algorithm is provided for calculating the weighting factors. PMID- 3340719 TI - Radioprotective action of WR-1065 on radiation-induced DNA strand breaks in cultured Chinese hamster ovary cells. AB - We have examined the radioprotective effect of WR-1065 on cultured Chinese hamster ovary cells. The effects of the drug on the induction and rejoining of gamma-ray-induced DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) were measured using alkaline (pH 12.1) and neutral (pH 7.0) elution, respectively. Molecular protection factors (PFs) calculated from these data allowed us to determine whether the degree of modification of strand breakage accurately predicted the PFs measured using the biological end point of cell survival. The drug did protect against the induction of both SSBs and DSBs, although to an extent that did not appear to fully account for the degree of radioprotection in terms of cell killing measured under identical conditions. It is therefore unlikely that radioprotection by WR-1065 occurs simply as a consequence of a general lowering of all types of gamma-ray-induced DNA lesions, and it is possible that the drug could differentially protect against the induction of subsets of these DNA lesions. The rate of SSB rejoining was retarded following preirradiation treatment of cells with WR-1065, but there was no effect on DSB rejoining. Postirradiation treatment with WR-1065 also appeared to retard SSB rejoining but without an accompanying effect on either DSB rejoining or cell survival; however, this effect was largely reversed by the addition of catalase and was therefore probably a result of H2O2 generated by autoxidation of the drug. Based on these observations, it would appear that the molecular actions of aminothiol radioprotective compounds that lead to reduced cell killing are much more complex than previously thought. PMID- 3340720 TI - Potentially lethal radiation damage repair and its inhibition by hyperthermia in normal hamster cells, mouse cells, and transformed mouse cells. AB - The capacity of plateau-phase Chinese hamster V79 and normal and transformed C3H 10T1/2 cells for repair of potentially lethal radiation damage (PLD) was evaluated for cells irradiated alone or given combined treatments of heat and radiation. The data show that all cell lines tested could repair PLD and that transformation to the tumorigenic state may reduce the capacity to repair PLD, especially if cells are evaluated at equal survival levels. Hyperthermia treatments before irradiation produced less sensitization than treatments after irradiation. In addition, hyperthermia treatment led to the inhibition of cellular capacity to repair PLD. This effect was the greatest for cells heated after irradiation, and repair of PLD could be completely eliminated. Several temperature isodose heat treatments were evaluated, and the lower temperature heat treatments were more effective in the inhibition of PLD than the higher temperature heat treatments; this is consistent with earlier results indicating temperature dependence in thermal radiosensitization (S. A. Sapareto et al., Int. J. Radiat. Oncol. Biol. Phys. 5, 343-347 (1979)). PMID- 3340721 TI - The repair of potentially lethal damage and sublethal damage in strains of mouse L5178Y lymphoma cells differing in radiation sensitivity. AB - Mouse lymphoma strains L5178Y-R (LY-R) and L5178Y-S (LY-S), which are differentially sensitive to the cytotoxic effects of ionizing radiation, were found to differ in their abilities to repair potentially lethal damage (PLD) and sublethal damage (SLD). The results showed that strain LY-R was more proficient than strain LY-S in the repair of SLD. The split dose recovery observed in strain LY-S could be accounted for by its recovery during postirradiation incubation. In contrast, SLD repair occurred in the absence of PLD repair in strain LY-R. The possibility that the repair of PLD might be completed prior to the postirradiation incubation in strain LY-R was suggested by the decreased survival observed when the cells were irradiated in a hypotonic solution. The repair of PLD and SLD in strain LY-S was temperature sensitive, occurring during postirradiation incubations between 15 and 34 degrees C, but not at 37 or 40 degrees C. This temperature sensitivity is very similar to the temperature sensitivity of the repair of pH 9.6-labile lesions in DNA in strain LY-S, as reported previously. Thus postirradiation cellular recovery processes in strain LY-S may involve the repair of pH 9.6-labile lesions in DNA. Temperature dependent changes in the postirradiation distribution of cells throughout the cell cycle were observed which could contribute to the temperature sensitivity of the postirradiation recovery of strain LY-S. PMID- 3340722 TI - Effects of the differentiating agents sodium butyrate and N-methylformamide on the oxygen enhancement ratio of human colon tumor cells. AB - We have previously shown that chronic adaptation of human tumor cells to the differentiation-inducing agents N-methylformamide (NMF) and sodium butyrate (NAB) increases the sensitivity of oxic cells to graded single doses of X rays. These studies were carried out to define the sensitivity of hypoxic cells after adaptation. Clone A colon tumor cells were grown for three passages in medium containing 170 mM NMF or 2 mM NAB and irradiated in suspension culture, after gassing with either oxygen (60 min) or ultrapure nitrogen (90 min), and complete survival curves were generated. Using the linear-quadratic equation to describe the data, it was found that NMF and NAB produced increased X-ray killing of hypoxic cells. At the 10% level of survival, the dose-modifying factors were about 1.20 and 1.25 for NMF- and NAB-adapted hypoxic cells, respectively, as compared to hypoxic control cells. However, since both oxic and hypoxic cells exhibited increased sensitivity after NMF and NAB adaptation, there was no major change in the oxygen enhancement ratio. PMID- 3340723 TI - The effect of N-methylformamide on radiocurability of murine tumors. AB - N-Methylformamide (NMF) is a polar solvent with maturational activity, i.e., it induces malignant cells to form more differentiated phenotypes. In addition, it renders tumor cells more sensitive to chemotherapeutic drugs and ionizing radiation. In the present study, NMF failed to augment radiocurability, as measured by the single-dose TCD50 assay, of two murine tumors: an 8-mm fibrosarcoma (FSA) and a 6-mm mammary carcinoma (MCA-K). NMF, at a dose of 300 mg/kg, was given ip daily for several days before and/or after local tumor irradiation. PMID- 3340724 TI - Long-term repair in vivo of colony-forming ability and chromosomal injury in X irradiated mouse hepatocytes. AB - The radiosensitivity of mouse hepatocytes in vivo was measured in terms of clonogenicity or chromosome damage (micronucleus production). Within 24 h of irradiation there was a dose-dependent increase in clonogenicity (dose-modifying factor, DMF = 1.37 +/- 0.09) followed by long-term repair which resulted in a DMF of 3.49 +/- 0.23 at 11 months. Such repair also took place, but to a lesser extent, after the end of fractionated irradiation. Cell proliferation, measured by tritiated thymidine autoradiography, was insufficient to explain the long-term reduction in radiosensitivity in terms of a dose-dependent replacement of damaged cells. Although there was a reduction in the frequency of cells with micronuclei, postirradiation, the magnitude of this decrease was relatively small; the DMF for micronucleus-free cells at 11 months was only 1.49 +/- 0.25. Thus the long-term increase in clonogenicity can only partially be explained in terms of repair of chromosome injury, assessed by the production of micronuclei. PMID- 3340725 TI - Dose fractionation and hepatocyte clonogens: alpha/beta congruent to 1-2 Gy, and beta decreases with increasing delay before assay. AB - The sensitivity to X-ray dose fractionation was assessed for hepatocytes forming colonies in fat pads in mice. When the cells were assayed 1 day after the last irradiation the alpha/beta ratio was 1.0-1.6 depending on the method of analysis. The alpha/beta ratio describing the shape of the single-dose survival curve was much higher, and it did not predict the response to fractionation. When the assay was delayed for 10 months after the fractionated irradiation, the alpha/beta ratio was 1.9-2.1, and the beta component showed the greatest change with time. It is concluded that hepatocytes respond to dose fractionation in a manner expected of a late-responding tissue, even when the cells are assayed as early as 1 day after the last dose. PMID- 3340726 TI - NMR imaging and spectroscopy of the mammalian central nervous system after heavy ion radiation. AB - NMR imaging, NMR spectroscopy, and histopathologic techniques were used to study the proton relaxation time and related biochemical changes in the rodent brain after in vivo helium beam irradiation with single doses of 10, 20, 30, and 50 Gy. Two-dimensional Fourier transform spin-echo imaging and saturation recovery with projection reconstruction were used to measure the NMR relaxation parameters. These parameters were correlated with proton spectroscopy and histopathology. Additional high resolution in vitro proton spectroscopy was performed on brain extracts to observe chemical changes that could not be seen in vivo. The major findings from these experiments were that at 4-14 days postirradiation, image intensity and T1 relaxation time decreased on the irradiated side and increased on the nonirradiated side relative to nonirradiated control animals. In vivo surface coil proton spectroscopy methods demonstrated changes in lipid and phosphatidylcholine (p-choline) peaks. In vitro studies of the aqueous fraction of brain extracts showed radiation-induced changes in lactate, 4-aminobutyric acid, and p-choline peak areas. In the organic fraction, radiation-induced changes were observed in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. With histology and Evans blue injections, blood-brain barrier alterations were seen as early as 4 days after a dose of 50 Gy. PMID- 3340727 TI - Safety of nuclear plants in the United States. PMID- 3340728 TI - Nuclear power: levels of safety. AB - The rise and fall of the nuclear power industry in the United States is a well documented story with enough socio-technological conflict to fill dozens of scholarly, and not so scholarly, books. Whatever the reasons for the situation we are now in, and no matter how we apportion the blame, the ultimate choice of whether to use nuclear power in this country is made by the utilities and by the public. Their choices are, finally, based on some form of risk-benefit analysis. Such analysis is done in well-documented and apparently logical form by the utilities and in a rather more inchoate but not necessarily less accurate form by the public. Nuclear power has failed in the United States because both the real and perceived risks outweigh the potential benefits. The national decision not to rely upon nuclear power in its present form is not an irrational one. A wide ranging public balancing of risk and benefit requires a classification of risk which is clear and believable for the public to be able to assess the risks associated with given technological structures. The qualitative four-level safety ladder provides such a framework. Nuclear reactors have been designed which fit clearly and demonstrably into each of the possible qualitative safety levels. Surprisingly, it appears that safer may also mean cheaper. The intellectual and technical prerequisites are in hand for an important national decision. Deployment of a qualitatively different second generation of nuclear reactors can have important benefits for the United States. Surprisingly, it may well be the "nuclear establishment" itself, with enormous investments of money and pride in the existing nuclear systems, that rejects second generation reactors. It may be that we will not have a second generation of reactors until the first generation of nuclear engineers and nuclear power advocates has retired. PMID- 3340729 TI - Thermoluminescence dosimetry of gamma rays from the atomic bomb at Hiroshima using the predose technique. AB - Thermoluminescence dosimetry measurements of gamma rays produced by the atomic bomb in Hiroshima were made by the predose technique using eight ceramic samples collected from five buildings located at distances between 1271 and 2051 m from the hypocenter. The results of our measurements are compared to both the newer dose estimates (Dosimetry System 1986) and older dose estimates (Tentative 1965 Doses) for survivors of the Hiroshima atomic bomb. In comparison with the older estimates, our results are larger by a factor of 2.3 at 1271 m and 3.9 at 2051 m. Our results and the newer estimates for Hiroshima differ by a factor of only 1.14 +/- 0.16 on the average. PMID- 3340730 TI - Relationship between attenuation coefficients and dose-spread kernels. AB - Dose-spread kernels can be used to calculate the dose distribution in a photon beam by convolving the kernel with the primary fluence distribution. The theoretical relationships between various types and components of dose-spread kernels relative to photon attenuation coefficients are explored. These relations can be valuable as checks on the conservation of energy by dose-spread kernels calculated by analytic or Monte Carlo methods. PMID- 3340731 TI - Factors influencing the oxidation of the radioprotector WR-1065. AB - N-(2-Mercaptoethyl)-1,3-diaminopropane (WR-1065) is the free thiol form of the radio- and chemoprotector S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR 2721). Interest currently exists in the clinical use of WR-2721 and WR-1065 as radio- and chemoprotectors of normal tissues. However, measurement of plasma levels of WR-1065 has proven difficult, due to rapid drug oxidation. Therefore, we studied factors influencing the oxidation of WR-1065, in Hepes-buffered saline as well as in tissue culture media containing 10% fetal bovine serum. The rate of oxygen consumption by WR-1065, as determined using the Clark oxygen electrode system, was faster in medium plus serum than in Hepes-buffered saline. That this effect is largely due to the presence of trace metal ions in tissue culture media and serum was indicated by the observation that addition of Cu2+ or Fe3+ to buffer stimulated oxygen consumption. Addition of KCN inhibited the reaction of WR-1065 with oxygen, and this effect was dependent on KCN concentration. That KCN blocked WR-1065 oxidation to the disulfide was verified using Ellman's reagent to quantitate the free thiol form. The rate of oxygen consumption was shown to be affected by temperature as well as concentration of WR-1065. Catalase reduced the rate of oxygen consumption of WR-1065, indicating that peroxide is formed in this system. Superoxide dismutase had a stimulatory effect. WR-1065 was found to stimulate the hexose monophosphate shunt in A549 cells. Since this stimulation was prevented by the presence of catalase, it appeared to be due to the response of the cells to peroxide, formed as a result of WR-1065 autooxidation. PMID- 3340732 TI - Evidence for a role of heat-shock proteins in proliferation after heat treatment of synchronized mouse neuroblastoma cells. AB - A role for heat-shock proteins (HSPs) in proliferation after heat treatment was considered in synchronized mouse neuroblastoma cells. For this purpose enhancement of HSP synthesis after heat treatment was inhibited by actinomycin D and the effect of this on cell cycle progression into mitosis and on cell survival was studied both in thermoresistant G1- and in thermosensitive late S/G2 phase cells. In G1-phase cells expression of basal and heat-induced HSP synthesis was the same as that in late S/G2-phase cells, which suggests that regulation of thermoresistance throughout the cell cycle is not directly linked with HSP synthesis. The synthesis of HSP36, HSP68, and HSP70 was enhanced after a 30-min treatment at 41-43 degrees C. Increase of HSP synthesis after heat shock was partly suppressed by the presence of 0.1 microgram/ml actinomycin D during heat treatment, while 0.2 micrograms/ml prevented enhancement of HSP synthesis completely. Suppression of heat-induced HSP synthesis by actinomycin D had the same concentration dependency in G1- and late S/G2-phase cells. Actinomycin D potentiated induction of mitotic delay by heat treatment (30 min, 42.5 degrees C) but only under conditions where it actually inhibited heat-induced enhancement of HSP synthesis. Heat-induced cell killing was also potentiated by actinomycin D. The potentiating effect of actinomycin D on heat-induced mitotic delay and on heat-induced cell killing was more pronounced in G1-phase cells than in late S/G2 phase cells. These results give evidence for a role of HSPs in the resumption of proliferation after heat treatment and suggest that heated G1-phase cells are more dependent on HSP synthesis for recovery of proliferation after heat treatment than heated late S/G2-phase cells. PMID- 3340733 TI - DNA double-strand break repair in eukaryotic cell lines having radically different radiosensitivities. AB - TN-368 lepidopteran insect cells are on the order of 100 times more resistant to the lethal effects of ionizing radiation than cultured mammalian cells. DNA double-strand breaks (DSB) are believed by many to be the critical molecular lesion leading to cell death. We have therefore compared the rejoining of DSB in TN-368 and V79 Chinese hamster cells. Cells were irradiated on ice with 137Cs gamma rays at a dose rate of 2.5 Gy/min, incubated for various periods of time, and assayed for DNA DSB using the method of neutral elution. The kinetics of DSB rejoining following a dose of 90.2 Gy is similar for both cell lines with 50% of the rejoining completed in about 12 min. Approximately 83 and 87% of the DSB are rejoined in the TN-368 and V79 cells, respectively, by 1 h postirradiation. However, no further rejoining occurs in the TN-368 cells through at least 6 h postirradiation, whereas approximately 92% of the DSB are rejoined in the V79 cells by 2 h postirradiation. Other studies (from 22.6 to 226 Gy) demonstrate that the amount of rejoining of DSB varies inversely with dose for both cell lines, but this relationship is not as pronounced for the TN-368 cells. In general, these findings do not support the hypothesis that unrejoined DNA DSB represent the critical molecular lesion responsible for cell death. PMID- 3340734 TI - Human epithelial teratocarcinoma cells (P3): radiobiological characterization, DNA damage, and comparison with other rodent and human cell lines. AB - Survival parameters and immediate DNA damage induced by 60Co gamma rays, 50-kVp X rays, and Janus fission-spectrum neutrons in human epithelial P3 cells (derived from an embryonic teratocarcinoma) are compared with those for Chinese hamster lung V79 cells. DNA damage caused by X and gamma irradiation, measured by alkaline elution methods, is the same in both cell types, whereas the P3 cells are about two times more sensitive (as measured by Do ratios of the final survival curve slope) to the lethal effects of these radiations than are the V79 cells. Human P3 cells are also more sensitive to the lethal effects of fission spectrum neutrons than V79 cells. Survival experiments with split radiation doses and hypertonic salt treatment indicate that both P3 cells and V79 cells can recover from radiation-induced damage efficiently. PMID- 3340735 TI - Life-shortening and disease incidence in C57Bl mice after single and fractionated gamma and high-energy neutron exposure. AB - C57Bl Cnb mice were exposed to single or fractionated d(50)+Be neutrons or 137Cs gamma-ray exposure at 12 weeks of age and were followed for life-shortening and disease incidence. The data were analyzed by the Kaplan-Meier procedure using as criteria cause of death and possible cause of death. Individual groups were compared by a modified Wilcoxon test according to Hoel and Walburg, and entire sets of different doses from one radiation schedule were evaluated by the procedure of Peto and by the Cox proportional hazard model. No significant difference was found in life-shortening of C57Bl mice between a single gamma and neutron exposure. Gamma fractionation was clearly less effective in reducing survival time than a single exposure. On the contrary, fractionation of neutrons was slightly although not significantly more effective in reducing life span than a single exposure. Life-shortening appeared to be a linear function of dose in all groups studied. The data on causes of death show that malignant tumors, particularly leukemias including thymic lymphoma, and noncancerous late degenerative changes in lung were the principal cause of life-shortening after a high single gamma exposure. Exposure delivered in 8 fractions 3 h apart was more effective in causing leukemias and all carcinomas and sarcomas than one delivered in 10 fractions 24 h apart or in a single session. Following a single neutron exposure, leukemias and all carcinomas and sarcomas appeared to increase somewhat more rapidly with dose than after gamma irradiation. No significant difference in the incidence of leukemias and all carcinomas and sarcomas was noted between a single and a fractionated neutron exposure. PMID- 3340736 TI - Time-temperature analyses of cell killing of synchronous G1 and S phase Chinese hamster cells in vitro. AB - Time-temperature analyses of durations of heating required to achieve isosurvival were used to compare hyperthermic cell killing of synchronous Chinese hamster ovary (CHO) cells heated in G1 or S at temperatures of 42 to 45.5 degrees C. G1 populations were obtained by incubation of mitotic cells for 90 min at 37 degrees C. S phase populations were obtained by incubation of mitotic cells for 12 h at 37 degrees C in medium supplemented with 2 micrograms/ml aphidicolin, a reversible inhibitor of DNA alpha polymerase; S phase survival was also determined in an aphidicolin-free system by using high specific activity [3H]thymidine. In both systems, the thermosensitivity was similar and decreased as the cells progressed from early S phase, in agreement with earlier studies (R. A. Read, M. H. Fox, and J. S. Bedford. Radiat. Res. 98, 491-505 (1984]. A comparison of Arrhenius plots of the inverse of durations of heating required to achieve isosurvival for cells heated in G1 or S phase showed similar temperature dependence above 43.5 degrees C, yet the plots for heat-sensitive S phase cells were offset from those for heat-resistant G1 cells by about 1.5 degrees C, i.e., S phase cells respond to 43 degrees C with a rate similar to that observed in G1 cells heated at 44.5 degrees C. Using least-squares regression of the semilog plots, the curves were analyzed either as continually bending curves or as two straight lines with a break at 43.5 degrees C. When the data were analyzed using two straight lines, no significant differences in the slopes of the time temperature plots of G1 or S phase cells were observed. A quantitative comparison between the two methods of data analysis demonstrated that in both phases the data were better fit with a continuously curving line, rather than two straight lines. PMID- 3340737 TI - Radiosensitivity of late recurrences following radiotherapy of murine fibrosarcomas. AB - Radiosensitivity of late recurrent tumors which emerged after radiotherapy was investigated. Tumors observed were fibrosarcomas. Recurrences emerged in the irradiated area approximately 200 days after a 50% tumor control dose of radiation of 60Co gamma rays or mixed irradiation with fast neutrons and gamma rays. The recurrent and radiation-induced tumors were differentiated by karyotype analysis. Once transplanted into fresh mice, the recurrent tumors grew more slowly than the original tumor. Tumorigenicity of the late recurrences was lower than that of the original tumor. Radiosensitivity of the late recurrences, which was examined using methods to assess control, tumor growth delay, and colony forming assays, was significantly higher than that of the original tumor. D0 values of hypoxic tumor cells were significantly smaller in two of the three recurrences compared to the original tumor. Oxic cells, when irradiated in vitro, also showed smaller D0 values for the recurrent tumors than the original tumor. Hypoxic cell fractions were between 0 and 14% in the late recurrences and 10% in the original tumor. These results are consistent with the hypothesis that radiotherapy causes mutation of tumor cells which results in increased radiosensitivity of surviving tumor cells. PMID- 3340738 TI - Radiosensitization, thiol oxidation, and inhibition of DNA repair by SR 4077. AB - The mechanism of radiosensitization by diazenedicarboxylic acid bis(N),N piperidide (SR 4077), a less toxic analog of diamide, was studied using Chinese hamster ovary cells. SR 4077 gave an average SER of 1.58 for postirradiation incubations of 0.5, 1.0, or 2.0 h. Intracellular GSH and protein thiols decreased rapidly following drug addition and GSSG increased. The GSH/GSSG ratio shifted to 1/1.6 after SR 4077 addition but returned to greater than 10/1 between 0.5 and 1.0 h. After 4 h, total intracellular GSH was only 58% of pretreatment level and extracellular GSSG increased. Protein thiols decreased to 18% of pretreatment values, recovered most rapidly between 0.5 and 1.0 h, and reached 87% of pretreatment level after 4 h. A decrease in DNA single-strand break repair as measured by alkaline filter elution rate over 0.5 h was seen, and the initial rate of repair was slower than in cells not treated with SR 4077. DNA double strand break repair as measured by neutral filter elution rate was delayed during the first hour after irradiation when cells were treated with SR 4077. The times for maximum radiosensitization, GSH and protein thiol oxidation and recovery, and DNA strand break repair kinetics were closely linked. We propose that a protein thiol(s) required in repair processes was reversibly oxidized during SR 4077 treatment. PMID- 3340739 TI - Lonidamine-induced, pH dependent inhibition of cellular oxygen utilization. AB - The inhibitory effect of lonidamine 1-(2,4-dichlorobenzyl)-1H-indazole-3 carboxylic acid on oxygen utilization by Chinese hamster ovary (CHO) and murine fibrosarcoma (FSa-II) cells was evaluated with a Clark oxygen electrode. The drug produced a small but statistically significant inhibition of oxygen uptake at normal pH (7.4) in CHO and FSa-II cells of 16 and 11%, respectively. However, at low pH (6.65) the inhibitory effect of lonidamine increased dramatically to 60% in both CHO and FSa-II cells. Because of the potential difference between tumor and normal tissue pH, lonidamine and similar drugs may be effective for selectively modifying oxygen utilization and concentration in tumor tissue which might lead to increased radiation and hyperthermic sensitization in tumors compared to normal tissue, resulting in an improvement in the therapeutic ratio. PMID- 3340740 TI - Tumor induction and life shortening in BC3F1 female mice at low doses of fast neutrons and X rays. AB - Extension of previous investigations at this laboratory regarding life shortening and tumor induction in the mouse has provided more complete dose-response information in the low dose region of X rays and neutrons. A complete observation of survival and late pathology has been carried out on over 2000 BC3F1 female mice irradiated with single doses of 1.5 MeV neutrons (0.5, 1, 2, 4, 8, 16 cGy) and, for comparison, of X rays (4, 8, 16, 32, 64, 128, 256 cGy). Data analysis has shown that a significant life shortening is observable only for individual neutron doses not lower than 8 cGy. Nevertheless, assuming a linear nonthreshold form for the overall dose-effect relationships of both radiation qualities, an RBE value of 12.3 is obtained for the 1.5 MeV neutrons. The induction of solid tumors by neutrons becomes statistically significant at individual doses from 8 cGy and by X rays for doses larger than 1 Gy. Linear dependence on neutron dose appears adequate to interpret the data at low doses. A separate analysis of ovarian tumor induction substantiates the hypothesis of a threshold dose for the X rays, while this is not strictly needed to interpret the neutron data. A trend analysis conducted on the neoplasm incidence confirms the above findings. Death rates have been analyzed, and a general agreement between the shift to earlier times of these curves and tumor induction was found. PMID- 3340741 TI - Thermotolerance in preirradiated intestine and its influence on time-temperature relationships. AB - The crypt compartment of mouse jejunum showed a transient increase in thermal susceptibility approximately 10 days after moderate X-ray doses to the abdomen (9 10 Gy). The increase in response was manifest as an increase in slope of the crypt dose-response curve but was limited to temperatures below 43 degrees C. As a result, the 43 degrees C inflexion in the Arrhenius plot (the relationship between treatment time and temperature) for thermal sensitivity of crypts was eliminated in preirradiated tissue, and the curve became monophasic over the range 42.0-44.5 degrees C. At temperatures below 42 degrees C, the curve again deviated. At supranormal temperatures of 42 degrees C and below, the durations of hyperthermia needed for measurable effect were sufficient to allow thermotolerance to be expressed within the heating period. Neither the threshold heating times nor this thermotolerance were affected by prior irradiation. In the temperature range 42-43 degrees C, an earlier development of thermotolerance could be demonstrated in control tissue by challenging with an acute high temperature heat treatment. This thermotolerance was eliminated in preirradiated tissue, resulting in the apparent increase in sensitivity. The findings support the view that the complex nature of the time-temperature relationship seen in normal tissue in vivo is a manifestation of the ability of the tissue to progressively acquire a thermotolerant state during treatment at temperatures below approximately 43 degrees C, so that the "intrinsic" sensitivity is modulated while being assessed. PMID- 3340742 TI - Correction to "Calorimetric measurement of the carbon kerma factor for 14.6-MeV neutrons" by J. C. McDonald. PMID- 3340743 TI - Recent advances in practical pediatric radiology. PMID- 3340744 TI - Disc space infection in children: magnetic resonance imaging. AB - The diagnosis of childhood intervertebral disc space infection is often delayed. Establishment of the correct diagnosis is imperative to preclude unnecessary procedures and to exclude other, more serious, diagnoses that would require aggressive management. MRI is a noninvasive technique that is very sensitive for disc space infection in children. PMID- 3340745 TI - Ultrafast computed tomography for infants and children. AB - Experience using ultrafast CT in the diagnostic evaluation of more than 50 infants and children indicates that this new technique is highly accurate and easily performed. Ultrafast CT offers several advantages compared to conventional CT. Scan times of either 0.05 or 0.1 seconds were sufficiently short to eliminate motion artifacts, even without patient sedation; sedation is a routine procedure for the conventional CT examination of most infants and small children and carries a finite risk. Procedure time appears to be shorter using ultrafast CT, 15 minutes or less, than with conventional CT. No control data using conventional CT are available for this patient population, but generally pediatric body CT studies are scheduled at hourly intervals at our medical center and are rarely completed in less than 30 minutes. Dynamic imaging alternatives for evaluation of the pediatric heart and airway include angiocardiography, digital subtraction studies, and fluoroscopy, which are limited by relatively high radiation exposure and by the inability to display all wall motions simultaneously due to their projectional rather than tomographic orientation. The potential for acquiring serial 0.05-second images of rapidly moving structures, including the heart, airway, and lungs, is unique to the ultrafast CT technique and facilitates the identification of functional abnormalities, including intracardiac shunts, valvular obstructions, tracheomalacia, and segmental bronchial obstruction. The relationships of mediastinal soft tissue structures and vessels are well defined by both ultrafast and conventional CT. In situations in which fine spatial resolution is pivotally important, the radiologist has the option with the C-100 scanner to select the 0.1-second scanning mode. This mode results in a higher radiation exposure per slice, approximately two-fold, and also uses an array of more closely spaced detectors, 864, to increase dose efficiency and spatial resolution. Although not generally required for our pediatric patients, one has the additional option of performing repeated 0.1-second images at any level, as many as ten exposures, totaling 1.0 seconds, to increase photon flux and increase resolution. Thus, the choice of scanning options can markedly influence both radiation dose, resolution, and contrast sensitivity characteristics. PMID- 3340746 TI - Chemonucleolysis. AB - In November 1982, the Federal Drug Administration approved Chymodiactin, chymopapain in injection form, for the treatment of herniated intervertebral discs. This procedure, termed chemonucleolysis, requires radiologic support. This article describes the anatomy, pathology, and special techniques related to chemonucleolysis and defines the role of the radiologic technologist in the completion of this procedure. PMID- 3340748 TI - An air-filled spinal column? PMID- 3340747 TI - Diffusion of an innovation: adoption of MRI. AB - "Diffusion of Innovation" is a marketing theory that predicts the pattern of adoption of new products, with specific characteristics of the product determining the rate of adoption. This article attempts to determine whether MRI fits the predicted pattern. A computer Medline search to assess the number of articles printed on MRI shows that MRI is being adopted more slowly than CT, but like CT, MRI is following the pattern predicted by the Diffusion Theory. PMID- 3340749 TI - The variable filter dial. PMID- 3340750 TI - Career success: A guide for the radiologic technologist. PMID- 3340751 TI - Clinical application of a record and verify system in radiation oncology. PMID- 3340752 TI - Test wiseness. AB - Most test will have some questions worded in such a way that the recall button is automatically triggered. Answer those questions first, utilizing the body of knowledge that has been accumulated from the course content and assignments. Answer the remaining questions on the test by applying the answer analysis techniques outlined above. Review the answers and make the necessary changes. The combination of knowledge and answer analysis techniques will improve the ability of students to pass all types of examinations. PMID- 3340753 TI - Ask READO. PMID- 3340755 TI - Notes on talking to sick and well. PMID- 3340754 TI - Restatement on certification article. PMID- 3340757 TI - Detection and staging of renal neoplasms: a reassessment of MR imaging. AB - The use of magnetic resonance (MR) imaging in the detection and staging of renal neoplasms was investigated in 104 patients with 106 renal cell carcinomas confirmed at surgery or autopsy. Overall, MR imaging demonstrated 101 of 106 lesions (95%), including all 93 tumors that were larger than 3 cm in diameter but only eight of the 13 smaller tumors (62%). MR imaging enabled accurate staging of 82% of all detected lesions but led to the understaging of nine lesions and the overstaging of nine. At present, MR imaging cannot be used as a screening modality for renal tumors. However, its negative predictive values of 98% and 99%, respectively, for the evaluation of tumor vascular extension and tumor spread to adjacent structures makes it an excellent staging modality that should be used when the CT findings are equivocal. MR imaging is not accurate in indicating bowel and mesentery involvement, but rapid technical advances and the introduction of bowel contrast medium may improve this present limitation. PMID- 3340756 TI - Invasive cervical carcinoma: comparison of MR imaging and surgical findings. AB - The accuracy of magnetic resonance (MR) imaging in staging invasive carcinoma of the cervix was determined retrospectively in 57 consecutive patients in whom the extent of disease was surgically confirmed. MR images were analyzed for (a) location and size of the primary tumor; (b) tumor extension to the uterine corpus, vagina, parametria, pelvic sidewall, bladder, or rectum; and (c) pelvic lymphadenopathy. The accuracy of MR imaging in determination of tumor location was 91% and for determination of tumor size within 0.5 cm, 70%. Its accuracy was 93% for vaginal extension and 88% for parametrial extension. Pelvic sidewall, bladder, and rectal involvement were accurately excluded in all patients, but the positive predictive values were 75%, 67%, and 100%, respectively. Overall, the accuracy of MR imaging in staging was 81%. MR imaging is valuable because it can accurately demonstrate tumor location, tumor size, degree of stromal penetration, and lower uterine segment involvement. It is also valuable for ruling out parametrial, pelvic sidewall, bladder, and rectal involvement. PMID- 3340758 TI - Aortic dissection: sensitivity and specificity of MR imaging. AB - Gated transverse magnetic resonance (MR) images of 54 patients (35 male, 19 female; aged 16-90 years) with suspected or known aortic dissection were reviewed by three cardiac radiologists without knowledge of clinical details. The reviewers independently determined the presence or absence and the type of aortic dissection. A confidence level was assigned for each diagnosis, and receiver operating characteristic curves were generated. The reviewer with extensive MR experience correctly identified 96% of the proved aortic dissections and all of the normal cases; the reviewer with moderate experience identified 96% and 84%, respectively; and the reviewer with minimal experience, 78% and 94%. The sensitivity at a specificity level of 90% was determined for each reviewer (100%, 96%, and 83%, respectively). MR imaging is highly sensitive and specific in the diagnosis of aortic dissection but does require considerable experience because of the need to recognize flow artifacts. PMID- 3340759 TI - MR imaging artifacts, ferromagnetism, and magnetic torque of intravascular filters, stents, and coils. AB - Experiments were conducted in which various intravascular filters, stents, and coils were imaged using magnetic resonance (MR) spin-echo technique at 0.35 T. These devices were also evaluated for ferromagnetism (at 0.35, 1.5, and 4.7 T), magnetic torque (at 0.35 and 1.5 T), and magnetically induced migration within a plastic tube (at 0.35 and 1.5 T for the Greenfield filter [GF]). The stainless steel GF was evaluated in vitro for its propensity to perforate canine inferior venae cavae (IVC). Magnetic force and torque at 1.5 T did not dislodge the GF or result in perforation of canine IVC by the GF. Beta-3 titanium alloy (used in a new percutaneous version of the GF) is apparently one of the best-suited metals for use with MR imaging because of its lack of ferromagnetism (up to 4.7 T) and absence of MR imaging artifacts (at 0.35 T). Devices composed of Elgiloy (Mobin Uddin filter), nitinol, and MP32-N (Amplatz filter) alloys all created mild artifacts. Devices fashioned from 304 and 316L (GF and Palmaz stent) stainless steel alloys created severe "black-hole" artifacts, with the 304 alloy devices also showing marked image distortion. Generally, the greater the ferromagnetism of a device, the greater its magnetic susceptibility artifact. PMID- 3340760 TI - Common bile duct calculi: updated experience with dissolution with methyl tertiary butyl ether. AB - The authors describe their experience with methyl tertiary butyl ether (MTBE) in a larger series of patients than previously reported in order to acquaint physicians with both its effectiveness for dissolution of common bile duct calculi and the limitations of its use. Ten patients with 13 biliary calculi underwent percutaneous stone dissolution treatment with the experimental cholesterol solvent, MTBE. Three stones completely dissolved within 30 minutes, seven were reduced in size, and three were visibly unaffected. All stones not completely dissolved were easily extracted by means of a stone basket except for one in a patient taken to surgery. Although MTBE perfusion is an effective technique for management of biliary calculi, practitioners should be aware that its use is quite time consuming and its odor difficult to control. PMID- 3340761 TI - Complications of embolization: analysis of 410 procedures. AB - Over a 10-year period, 284 patients underwent 410 embolization procedures because of liver, renal, or bone tumors; gastrointestinal bleeding; systemic or pulmonary arteriovenous malformations; and other miscellaneous lesions. A wide range of particulate and liquid embolic agents were used. The complications were analyzed with respect to the patient's underlying abnormality. Minor complications occurred after 16.3% of procedures, serious complications after 6.6%, and death after 2%. The postembolization syndrome (fever, elevated white blood cell count, and discomfort) was encountered after 42.7% of the procedures, and in 43.7%, no significant adverse reactions were documented. The major complications and deaths were encountered in patients with a serious underlying abnormality in whom no alternative form of treatment was available and who were extremely sick prior to the procedure. When considered in relationship to the natural progress of the disease and the lack of other treatment options, the overall complication rate seems acceptable. PMID- 3340762 TI - Spinal abnormalities in pediatric patients: MR imaging findings compared with clinical, myelographic, and surgical findings. AB - Eighty-one pediatric patients with a variety of spinal disorders, including suspected dysrhaphism, scoliosis, neoplasia, and neurofibromatosis, underwent magnetic resonance (MR) imaging. The results were retrospectively compared with those of myelography followed by computed tomography (CT) and surgery. In patients with dysrhaphism, most abnormalities, including hydromyelia, inclusion tumors, and sites of cord tether, were demonstrated with MR imaging. Diastematomyelia and small hydromyelic cavities were indistinguishable on routine coronal and sagittal T1-weighted images; axial images with T2 weighting were optimal for this differentiation. MR imaging did not enable direct visualization of a thickened filum or evaluation of tethering with a thin, dorsally positioned neural placode. Congenital or severe scoliosis required lengthy studies with multiple planes of imaging or myelography and CT. Milder curvatures were readily evaluated with MR imaging, and neoplastic lesions, with the exception of intrathecal tumor seeding, were adequately defined. PMID- 3340763 TI - Gd-DOTA: characterization of a new paramagnetic complex. AB - The relaxivity, biodistribution, and toxicity of the gadolinium tetraazacyclododecanetetraacetic acid (Gd-DOTA) complex were evaluated. This cyclic complex has much greater in vitro stability (10(28)) than similar noncyclic complexes such as gadolinium-diethylenetriaminepentaacetic acid (Gd DTPA) (10(23)) or gadolinium-ethylenediaminetetraacetic acid (Gd-EDTA) (10(17)). The T1 relaxivity of Gd-DOTA (meglumine salt) determined in saline and in liver tissue at 20 MHz was similar to the relaxivity of Gd-DTPA. Tissue proton relaxation enhancement (PRE) correlated closely with chemical measurement of tissue gadolinium concentration. In rats, the biodistribution of Gd-DOTA was similar to Gd-DTPA with a distribution half-life of 3 minutes and an elimination half-life of 18 minutes. The median lethal dose (LD50) in mice of Gd-DOTA was 93% higher than that of Gd-DTPA; the calculated safety factor (ratio of LD50 to effective dose) was 53 for Gd-DOTA and 28 for Gd-DTPA. The data suggest that in vitro stability correlates with in vivo safety. PMID- 3340764 TI - Obstructive pneumonitis: a pathologic and pathogenetic reappraisal. AB - It is widely accepted that pneumonitis distal to an obstructing airway tumor is the result of infection. The authors performed a prospective study to reevaluate this concept and to clarify the nature of the pathologic findings underlying the observed radiographic changes. Specimens were examined for 50 consecutive patients undergoing resection of pulmonary carcinoma. Histologic changes interpreted as noninfectious were found in 42 cases. Findings suggestive of recent or remote infection were also present in nine of these 42 specimens and were localized predominantly in relation to small- to medium-sized airways (acute bronchitis or bronchiolitis); these changes were always present in a background of noninfectious pneumonitis. The authors conclude that the radiographic changes seen in airway obstruction in surgically excised lungs are usually due to consolidation of lung parenchyma by a noninfectious process. When infection does occur, it involves primarily the airways and is not likely to be radiographically detectable. PMID- 3340765 TI - Pulmonary lymphangitic carcinomatosis: CT and pathologic findings. AB - The authors retrospectively reviewed the computed tomographic (CT) scans, biopsy specimens, autopsy results, and lobectomy specimens of 21 patients who had lymphangitic carcinomatosis. Ten-millimeter collimation CT scans were obtained from all patients, and selected 1.5-mm CT scans were obtained from ten patients. In five patients, the diagnosis was established with open lung biopsy, lobectomy, or autopsy; in nine, with bronchial biopsy or transbronchial biopsy; and in seven, with clinical and radiologic criteria. Certain characteristic findings on CT scans were evident: uneven thickening of bronchovascular bundles, thickening of isolated interstitial lines, and the presence of polygonal lines. These findings may be seen on CT scans even if the findings on chest radiographs are normal or nonspecific. The pathologic basis for these characteristic CT findings may relate to tumor thrombi in lymphatic vessels rather than edema and fibrosis, at least in the early stages of disease. PMID- 3340766 TI - Pulmonary melioidosis: clinical-radiologic correlation in 183 cases in northeastern Thailand. AB - The chest radiographs of 183 patients with pulmonary melioidosis seen over a 4 year period were evaluated retrospectively. Disseminated nodular lesions occurred in 46 of 55 patients (84%) with the acute septicemic form of the disease and in 17 of 31 (55%) with the subacute or chronic form and positive blood cultures. Alveolar lesions occurred in 26 of 50 patients (52%) with the acute pneumonic form. There was no typical pattern of pulmonary infiltrates in 16 patients with the subacute pneumonic form, but in the chronic form, 17 of 31 patients (55%) had mixed infiltrates with cavities. The lesions were confluent in the upper lobes but tended to spare the apices in nonsepticemic cases. Rapid progression and early cavitation are distinctive features in acute cases, but in chronic cases the lesions may remain unchanged up to 20 months. Pleural effusion or empyema was seen in 22 of 105 patients (21%) with acute disease and four of 31 (13%) with chronic disease. Six of 105 patients (6%) with acute disease and three of 31 (10%) with subacute or chronic disease and positive blood cultures had pericardial involvement. PMID- 3340767 TI - Sagittal orientation of the anterior minor fissure: radiography and CT. AB - Chest radiographs of 12 patients revealed an oblique, predominantly cephalocaudal linear opacity in the anterior inferomedial aspect of the right lung. Correlation with high-resolution computed tomography in two patients indicated that this opacity represented a sagittal orientation of the anterior minor fissure, with resultant inferomedial curving of the right upper lobe of the lung along the right border of the heart. The sagittal anterior minor fissure may extend inferiorly to the right hemidiaphragm and merge superiorly with the horizontal minor fissure. Autopsy findings in one case showed that this anatomic variant may explain potentially confusing radiographic manifestations of disease in the anterior segment of the right upper lobe of the lung and in the medial segment of the right middle lobe of the lung. PMID- 3340768 TI - Neofissure after right upper lobectomy: radiographic evaluation. AB - Following lobectomy of the right upper lobe of the lung, a single fissure, the neofissure, separates the right middle and lower lobes. In 25 patients in whom chest radiographs and computed tomographic (CT) scans were obtained after right upper lobectomy, the neofissure was identifiable to some extent on the radiographs in seven (28%) and on CT scans in 24 (96%). Among those patients in whom the neofissure was seen in its entirety, in 12 of 20 (60%) it was oriented predominantly in the coronal plane, paralleling the course of the original major fissure but displaced anteriorly and superiorly. In seven of 20 patients (35%) the superior aspect was coronal, rotated clockwise toward the sagittal plane inferiorly. In one of 20 patients (5%) the neofissure was oriented predominantly in the sagittal plane. The right middle lobe lies anterior and medial to the neofissure; the right lower lobe lies posterior and lateral. PMID- 3340769 TI - Right middle lobe collapse following right upper lobectomy. AB - Radiographic and computed tomographic (CT) examinations of the chest in four patients with collapse of the right middle lobe of the lung after lobectomy of the right upper lobe were reviewed. The diagnosis of collapse was made on the basis of findings of increased density in the right middle lobe and volume loss evidenced by displacement of the neofissure seen at CT. Plain radiographic findings included opacity in the right hilar and paramediastinal areas in all four patients, with smooth margination simulating mediastinal widening in three. PMID- 3340770 TI - Asbestos-related pleural and parenchymal fibrosis: detection with high-resolution CT. AB - Twenty-nine subjects with occupational asbestos exposure and clinical asbestosis were examined with high-resolution computed tomography (HRCT) to determine its sensitivity, relative to that of conventional computed tomography (CT), for detection of benign asbestos-related disease. Thin-section HRCT scans were obtained at five discrete levels through the mid and lower thorax in both prone and supine positions. The same technique was used in 34 age-similar control patients. Parenchymal abnormalities were seen most frequently in the posterior portion of the lung bases in the asbestos-exposed subjects. HRCT prone scans enabled basal structural abnormalities to be reliably distinguished from gravity related physiologic phenomena in 25 asbestos-exposed subjects. HRCT was more sensitive than CT in detection of both pleural and parenchymal fibrosis. In subjects with clinical asbestosis, HRCT demonstrated parenchymal abnormality in 96%, compared with 83% for CT. Similarly, pleural thickening was shown in 100% of subjects at HRCT, compared with 93% at CT. HRCT could be an important adjunct in the evaluation of asbestos-related pleuroparenchymal fibrosis. An HRCT study including prone scans is a sensitive, reliable means of detecting thoracic abnormalities in asbestos-exposed individuals. PMID- 3340771 TI - Calcification in untreated mediastinal lymphoma. AB - Calcification was demonstrated radiographically within newly diagnosed lymphoma of the mediastinum in two patients. These patients and those in other isolated reports show that radiographic examinations may, rarely, reveal calcification in lymphomatous tissue prior to treatment. PMID- 3340772 TI - Enterovenous fistula: unusual complication of Crohn disease. AB - An unusual complication in a patient with Crohn enterocolitis is presented. Ultrasound and computed tomographic studies showed stationary gas in the portal vein, and a presumptive diagnosis of septic ascending portal thrombophlebitis was made. Emergency laparotomy was performed and the terminal ileum was excised for recurrent Crohn disease. Pathologic examination showed a fistula from the lumen of the inflamed segment to the superior mesenteric venous system. Autopsy 1 month later showed organizing thrombi and fecal debris in the portal venules. PMID- 3340773 TI - Metastatic colon cancer: correlation of oxygen levels with I-131 F(ab')2 uptake. AB - Tumor oxygen levels were measured with an electrode in 13 patients with colon carcinoma metastases. These measurements were correlated with images obtained with radiolabeled monoclonal antibody 1083-17-1A. Only those tumors or tumor regions with a mean PO2 of 16 mm Hg or greater were successfully imaged. Tumors and tumor regions with a mean PO2 of less than 16 mm Hg were not imaged, even when the presence of antigen was confirmed with biopsy. These data suggest that physiologic factors other than antigen expression may affect antibody uptake. PMID- 3340774 TI - In-111-labeled liposomes: dosimetry and tumor depiction. AB - Neutral phospholipid vesicles (liposomes) were loaded with 0.5 mCi (18.5 MBq) indium-111 and administered to 24 patients with various types of cancer. The median diameter of the liposomes was 77 nm, and lipid dose was 0.78-6.25 mg/kg. Scans obtained 24 and 48 hours after injection of In-111 liposomes showed gradual blood clearance with homogeneous uptake in the normal liver and spleen. Dosimetric estimates for these organs were 2.3 +/- 1.1 and 2.3 +/- 1.4 rad (.02 +/- .01 Gy), respectively, with a whole-body estimate of 0.28 rad (.003 Gy). Radiation dose did not correlate with lipid dose. Total renal excretion of In-111 was less than 2% of the injected dose in all but two patients. Transient eosinophilia occurred in two patients. Tumor was seen in the scans of 22 of 24 patients (unbinded readings). In-111-labeled liposomes may enable the demonstration of suspected or unsuspected sites of tumor. PMID- 3340775 TI - Inflammation: imaging with Tc-99m HMPAO-labeled leukocytes. AB - Leukocytes labeled with technetium-99m hexamethylpropyleneamine oxime (HMPAO) were used in 100 patients: 32 with suspected inflammatory bowel disease, 17 with fever of unknown origin, 21 with suspected abdominal sepsis, 20 with suspected bone sepsis, seven with bronchiectasis, and three with recent myocardial infarction. The distribution of activity in patients subsequently shown not to have inflammatory bowel disease was similar to that previously described for indium-111-labeled leukocytes. However, in this study, activity was also seen in the kidneys and bladder and occasionally the gallbladder on both early (1-3 hours) and late (24 hours) views, and in the colon in late views. Migration of Tc 99m-labeled granulocytes was seen in inflammatory disease as early as 30 minutes after injection, while normal bowel activity was not seen before 4 hours. The sensitivity of Tc99m-labeled leukocytes in the detection of inflammation was 100%, the specificity was 95%. PMID- 3340776 TI - A circuit modification that improves mammographic phototimer performance. AB - The typical mammographic phototimer does not track with breast thickness. For four common, relatively new mammographic units, phototimed density decreases markedly as breast thickness increases. This trend is attributed to three factors: beam hardening, film reciprocity law failure (RFL), and photosensor dark or leakage current. The contributions of these three factors were experimentally quantitated for the phototimer of a Senographe 500T mammography unit. For a phototimed 28-kVp nongrid technique, the density varied from 2.0 for a 2.5-cm thick phantom to 0.3 for one 7.6 cm thick. Of the 1.7 difference in film density, 1.1 was attributed to beam hardening, 0.2 to RFL, and 0.4 to photomultiplier tube dark current. A circuit modification was installed in the phototimer that offsets the photomultiplier dark current and has a nonlinear response to compensate for beam hardening and RFL effects. The modified phototimer tracked to within +/- 0.06 density for a 28-kVp grid technique as phantom thickness was varied from 2.0 to 6.0 cm. Similar results were obtained for nongrid techniques. PMID- 3340777 TI - Dental material artifacts on MR images. AB - Magnetic resonance (MR) imaging of the head and neck is becoming an important aid in evaluating pathologic conditions of the brain, midface, and pharynx. Certain dental materials cause artifacts during MR imaging of the lower midface. These artifacts can obscure the normal anatomy. This study describes the degree of artifact production caused by various materials commonly used in dental restorations. Of the materials tested, those causing artifacts were made of stainless steel, such as orthodontic bands used for braces, and pins or posts that are commonly drilled into teeth to provide structure or stability before filling. Materials used as temporary or permanent fillings or crowns--such as amalgam, gold alloy, aluminum, microfilled resin, and polyvinyl acrylics--did not cause artifacts in the images. PMID- 3340778 TI - Complex fractures of the clivus: diagnosis with CT and clinical outcome in 11 patients. AB - During a 20-month period, fractures of the clivus occurring after craniocerebral trauma were diagnosed with computed tomography (CT) in 11 patients. Five patients had longitudinally oriented fractures; these were fatal in four patients due to either vertebral-basilar artery occlusion, brain stem trauma, or both. Six other patients had transversely oriented fractures that extended through the carotid canal and petrous temporal bone. While less frequently contributing directly to mortality, transverse fractures were also associated with cerebrospinal fluid leaks (two patients) and a cavernous sinus-carotid fistula (one patient). They were not as frequently associated with Horner syndrome or cranial nerve deficits as suggested in the current literature. This retrospective evaluation reveals two distinct injury patterns that demonstrate a difference in related morbidity and mortality. PMID- 3340779 TI - Sensitivity of Gd-DTPA-enhanced MR imaging of benign extraaxial tumors. AB - The effect of gadolinium diethylenetriaminepentaacetic acid (DTPA) on the sensitivity of cranial magnetic resonance (MR) imaging was measured in a prospective blinded study. Twenty-two consecutive patients with benign extraaxial tumors underwent MR imaging on a 1.5-T system without and with intravenous administration of Gd-DTPA. Readers independently interpreted the unenhanced and enhanced images without clinical information. The interpretations were compared with the anatomically verified diagnoses. Gd-DTPA improved the sensitivity of MR imaging for benign extraaxial tumors, especially in cases of residual or recurrent acoustic neuromas, multiple tumors (e.g., neurofibromatosis), or inconclusive unenhanced MR images. Enhancement with Gd-DTPA impaired the identification of a skull base tumor. PMID- 3340780 TI - Cavernous hemangiomas of the spinal cord: MR imaging. AB - In three patients with histologically proved cavernous hemangiomas of the spinal cord, magnetic resonance (MR) imaging was superior to myelography, delayed computed tomography (CT) myelography, and contrast-enhanced CT in depicting the lesion. The presence of mixed subacute and chronic hemorrhage, suggested by mixed high- and low-signal-intensity components of these lesions on MR images, may be characteristic of this rare, intramedullary vascular malformation. PMID- 3340781 TI - Traction osteophytes of the lumbar spine: radiographic-pathologic correlation. AB - Previous reports have emphasized two types of osteophytes on the anterior aspects of the lumbar vertebral bodies: the common claw osteophyte and the less common but more significant traction osteophyte, which is indicative of spinal instability. To delineate the importance of the traction osteophyte, a radiographic-pathologic study was conducted. The results indicate that claw osteophytes are more frequent than traction osteophytes, that both may coexist in a single vertebral body, and that, in most cases, these osteophytes appear to represent different stages of the same pathologic process. PMID- 3340783 TI - Infection versus tumor in the spine: criteria for distinction with CT. AB - To develop criteria to distinguish among pyogenic infection, nonpyogenic infection, and neoplastic processes in the spine by means of computed tomography (CT), the authors retrospectively analyzed 17 cases of pyogenic infection (20 sites), 40 cases of neoplastic disease (56 sites), and five cases of granulomatous infection (eight sites). Reliable criteria for pyogenic infection were complete prevertebral soft-tissue involvement, diffuse osteolytic destruction, gas within both bone and soft tissue, and a process centering on an intervertebral disk. Neoplastic disease was characterized by posterior element involvement, partial or absent prevertebral soft-tissue swelling, and osteoblastic alterations. In a limited number of cases, nonpyogenic infection was characterized by focal lytic bone involvement and marginal sclerosis. Blinded testing of these criteria indicated potential for improved diagnostic accuracy in clinical practice. PMID- 3340782 TI - Vertebral bone density in children: effect of puberty. AB - To determine changes in bone density during growth, trabecular vertebral density and an index of spinal cortical bone were measured with quantitative computed tomography in 101 children. The children were divided by age into three groups: prepubertal, indeterminate, and pubertal. Compared with prepubertal children, pubertal adolescents had significantly higher trabecular bone density and more compact bone in the spine (P less than .001). After controlling for puberty, vertebral bone density failed to correlate significantly with age, sex, weight, height, surface area, and body mass index. The results indicate that bone density increases markedly during puberty. PMID- 3340784 TI - Patterns of femoral head migration in osteoarthritis of the hip: a reappraisal with CT and pathologic correlation. AB - Although medial, superior, and axial patterns of migration of the femoral head in osteoarthritis of the hip have been well described, it is not clear what anatomic and biomechanical factors determine the direction of migration. The authors studied 22 patients with bilateral (11 patients) or unilateral (11 patients) osteoarthritis by means of conventional radiography and computed tomography (CT) to define any relationships between migration in the coronal plane and that in the transverse plane and to determine whether femoral anteversion, acetabular anteversion, femoral neck-shaft angle, or acetabular inclination were related to particular migration patterns. Anterior migration was evident in 14 of the 19 hips with a superior migration pattern, whereas posterior migration was present in five of the seven hips with a medial migration pattern. In the remainder of cases, no migration in the transverse plane was present. Femoral anteversion as determined with CT, femoral neck-shaft angle, angle of acetabular inclination, and acetabular anteversion angle in this relatively small sample were all found to be within normal limits and appeared to have no influence on the occurrence of a specific pattern of femoral head migration. PMID- 3340785 TI - Anterior cruciate ligament tears: MR imaging compared with arthroscopy and clinical tests. AB - Seventy-nine magnetic resonance (MR) studies of the knee were reviewed in an evaluation of the ability of MR imaging to demonstrate arthroscopically proved anterior cruciate ligament (ACL) tears. MR findings were also compared with the findings of two commonly applied clinical tests of ACL instability: the Lachman test and the anterior drawer test. The sensitivity of MR imaging was 94% (17 of 18), compared with 78% (14 of 18) for the anterior drawer test and 89% (16 of 18) for the Lachman test. The specificity was 100% for all three. Three MR criteria were applied: irregularity or a wavy contour of the anterior margin of the ligament, high-signal-intensity change within the substance of the ligament on T2 weighted images, and discontinuity of that substance. The sagittal T2-weighted image was especially helpful, producing an "arthrographic" effect, in which the anterior margin of the ACL is outlined by high-signal-intensity joint fluid. By demonstrating ACL and other extrameniscal lesions, MR imaging may help clarify the mechanisms of knee injury. PMID- 3340786 TI - Fast three-dimensional MR imaging of the knee: comparison with arthroscopy. AB - Twenty patients with suspected internal derangement of the knee were examined with fast, three-dimensional (3D) magnetic resonance (MR) imaging and arthroscopy with a numerical classification system designed for use by both the radiologist and orthopedist. MR volume acquisitions allowed delineation of all arthroscopically diagnosed meniscal tears and high-grade meniscal degeneration. All arthroscopically visible ligamentous injuries, including partial cruciate tears, were detected with MR imaging. There was excellent correlation for high grade cartilaginous lesions, although MR imaging appeared insensitive to small cartilage irregularities. Additionally, MR imaging allowed diagnosis of ten bone abnormalities not accessible to arthroscopic evaluation. The high accuracy of MR imaging that was found in this study was in large part due to the thin, contiguous sections generated in volume imaging. With the added advantage of high patient throughput, fast volume MR imaging is an accurate and efficient method for evaluation of knee abnormality. PMID- 3340787 TI - Snapping tendon syndrome: hip tenography with fluoroscopic monitoring. AB - The snapping tendon syndrome may be caused by abnormalities of the fascia lata, gluteus maximus muscle, or less commonly, the iliopsoas tendon. One case is reported in which fluoroscopic monitoring after computed tomography-guided injection of contrast material confirmed the diagnosis of snapping iliopsoas tendon syndrome. PMID- 3340788 TI - In-plane vascular imaging: pulse sequence design and strategy. AB - Magnetic resonance (MR) angiography is a noninvasive method of obtaining images without contrast agents. Recent developments in sequence design have allowed images of moving spins to be obtained without a loss of signal by rephasing the spins with three or four gradient pulses to compensate for constant velocity or acceleration, respectively. At longer echo times (TE), this approach allowed for low readout gradients and high signal-to-noise ratios. Angiograms with a resolution of 300 micron were obtained. With additional sequences that allow some dephasing but minimal signal loss, separate images of arteries and veins were obtained. Phase information was used to estimate flow velocity. Application of the rephasing scheme to gradient-echo sequences allowed for ungated, fast MR angiograms. Acceleration correction was important for long TE sequences, but velocity-corrected, gradient-echo sequences with a very short TE were comparable to velocity- and acceleration-corrected, gradient-echo sequences with slightly longer TEs. With ungated three-dimensional, gradient-echo sequences, susceptibility artifacts were minimized and excellent contrast-to-noise ratios were obtained. PMID- 3340789 TI - Adaptive histogram equalization in digital radiography of destructive skeletal lesions. AB - Adaptive histogram equalization, an image-processing technique that distributes pixel values of an image uniformly throughout the gray scale, was applied to 28 plain radiographs of bone lesions, after they had been digitized. The non equalized and equalized digital images were compared by two skeletal radiologists with respect to lesion margins, internal matrix, soft-tissue mass, cortical breakthrough, and periosteal reaction. Receiver operating characteristic (ROC) curves were constructed on the basis of the responses. Equalized images were superior to nonequalized images in determination of cortical breakthrough and presence or absence of periosteal reaction. ROC analysis showed no significant difference in determination of margins, matrix, or soft-tissue masses. PMID- 3340790 TI - Enhancement of parallel MR image acquisition by rotation of the plane of section. AB - The technique of simultaneous acquisition of magnetic resonance images from two different locations was combined with a modification of a commercially available oblique multisection method. By angling the sections slightly from the coronal plane and rotating the subject, simultaneous sections can be obtained within the given repetition time through both regions without a loss of the signal-to-noise ratio that would result from the use of true coronal sections. The technique has allowed simultaneous imaging of both shoulders and, with rotation of the subject, both knees. PMID- 3340792 TI - Femoral artery compression device for outpatient angiography. AB - To avoid late bleeding from the femoral artery puncture site after outpatient femoral angiography, a compression device was designed to exert continuous pressure over the groin, even when the patient is upright. It has been successfully used in more than 2,000 arterial catheter procedures. The device can also help prevent bleeding in patients who are at increased risk because of hypertension or anticoagulant therapy. PMID- 3340791 TI - Translumbar catheter angiography with a needle-sheath system. AB - Translumbar catheter angiography with a new needle-sheath system was used in 175 patients and proved to be a safe and simple technique. No complications related to aortic puncture or catheter manipulation were observed. The 5-F sheath allowed the introduction of 4-F catheters of different lengths and shapes. Results of computed tomography performed after the procedures in ten patients, and intraoperative findings obtained in 22 patients, showed only minimal hematomas in the retroperitoneal space. PMID- 3340793 TI - Defecography commode. AB - A mobile wooden commode was designed and built for use in defecography. The commode is made of 1/2-inch-thick plywood with birch veneer and a solid clear pine seat. Water or copper sheets are recommended for radiation filtration. A radiopaque ruler attached to the commode with a spring enables midline measurements. The modifications suggested by the authors have helped with setup and have improved the images acquired. PMID- 3340794 TI - The role of MR imaging in staging of cervical carcinoma. PMID- 3340795 TI - Considerations in the choice of contrast media for MR imaging. PMID- 3340796 TI - Beer company more ethical than medical community? PMID- 3340797 TI - Noninvasive bone densitometry: the need for cooperation and respect in research. PMID- 3340798 TI - Use of CT in acute trauma victims. PMID- 3340799 TI - Equipment choices for mammography. PMID- 3340800 TI - Flow velocity in cerebral arteries in the newborn. PMID- 3340801 TI - Molecular genetics in medicine. Introduction. PMID- 3340802 TI - Molecular genetics in medicine. PMID- 3340803 TI - The role of exercise in cardiac rehabilitation: a nursing perspective. PMID- 3340804 TI - The ventilator-dependent child: challenge and opportunity. PMID- 3340805 TI - Force field analysis: a person-centered approach to behavioral change. PMID- 3340806 TI - Documenting client education in rehabilitation: an interdisciplinary approach. PMID- 3340807 TI - Cost containment in spinal cord injuries. PMID- 3340808 TI - Reader survey report. PMID- 3340809 TI - A nursing framework for multidisciplinary rehabilitation. PMID- 3340810 TI - Interaction between SO2 and cold-induced bronchospasm in anesthetized rabbits. AB - In anesthetized, paralyzed and artificially ventilated rabbits, reflex changes in lung resistance induced by cooling the inspired air from 38 to 15 degrees C were studied before and after 45 min periods of SO2 exposure at two different concentrations (0.5 or 5 ppm). Both concentrations of SO2 induced significant increase in RL in intact animals (+16% and +50%, respectively). The effect of 5 ppm SO2 persisted after vagotomy. The cold-induced bronchospasm was halved after exposure to 0.5 ppm SO2 and was no longer significant after exposure to 5 ppm SO2. In both cases, RL recovered to control values 40 min after the end of SO2 exposure and then, the magnitude of cold-induced bronchospasm also recovered. The reflex bronchoconstrictor response to phenyldiguanide (PDG) i.v. disappeared after exposure to 5 ppm SO2. However, the bronchomotor response to histamine i.v., which involved both reflex and direct actions on airway smooth muscle, was not altered. These results show that (1) prolonged increase in RL measured after SO2 exposure does not result from a vagal reflex; (2) the cold-induced bronchospasm, as well as the bronchomotor response to PDG, are reduced or suppressed during the period where the effect of SO2 persisted. This suggests that 45 min exposure to SO2 induces transient alterations in tracheobronchial wall, which reduce the accessibility to nervous receptors in the airways. PMID- 3340811 TI - Aeration of the shell membranes of avian eggs. AB - The inner and outer shell membranes (ISM, OSM) of fertile hen's eggs become aerated during the first ten days of incubation. The volume of gas in the compound membrane increases from 0 to 65% by day 11 when practically all of the space between the fibers is gas filled. The amount of gas depends on a balance between the capillary tension produced by fluid menisci in the interstices between fibers and the colloid osmotic tension of the albumen. Capillary tension, measured directly with a pressure plate apparatus, and colloid osmotic pressure, measured with a new technique, are in virtual equilibrium during aeration. These tensions increase from 0.15 bar at laying to 2.25 bar on day 11 because of evaporation from the membranes and active removal of water from the albumen by the embryo. Water leaving the membranes by evaporation is only partly replaced from the albumen. Thus the water contents of the membranes and albumen decrease (ISM: 79 to 56%, OSM: 71 to 52%, albumen: 86 to 58%). As the membranes dry, gas enters the larger pores first. Physiological estimates of effective radius show smaller (x = 1.3 micrograms), bimodally distributed pores in the ISM and larger (x = 3.4 micrograms), unimodally distributed pores in the OSM. PMID- 3340812 TI - Central origin of the hypoxic depression of breathing in the newborn. AB - These studies were designed to ascertain whether the mechanism underlying the depressive component of the response to hypoxia in the newborn is similar to that in the fetus. We studied the response to hypoxia in 5-10 day old unanaesthetized rabbit pups before and after decerebration at or near the level of the midbrain/pontine junction. In the intact animal, hypoxia caused an initial stimulation of minute volume (VE) followed by a depression which was due to a decrease in both tidal volume (VT) and respiratory frequency (f). Decerebration abolished the depressive component of the response; the initial increase in VE on exposure to 7% O2 was now maintained, mainly due to a sustained increase in VT. We conclude that there is a central mechanism sited in or above the upper pons which is involved in the depressive component of the biphasic response to hypoxia. It is likely that this mechanism is similar to that mediating the hypoxic depression of breathing in the fetus. PMID- 3340813 TI - Oxygen binding characteristics of the hemocyanins of two deep-sea hydrothermal vent crustaceans. AB - Effects of pH and temperature on hemocyanin oxygen binding were examined using dialyzed blood from the hydrothermal vent crustaceans Bythograea thermydron (Brachyura) and Alvinocaris lusca (Caridea); blood samples were dialyzed against physiological salines having the same inorganic ion concentration as the blood. Hemocyanin of dialyzed B. thermydron blood demonstrated the highest O2 affinity at 10 degrees C (P50 = 1.8, 3.4 and 4.5 Torr at pH = 8.01, 7.7 and 7.4, respectively), with lower affinities at both higher and lower temperatures for all experimental pH values. A moderate Bohr effect (delta logP50/delta pH = -0.34 to -0.67) was found at all experimental temperatures (2-20 degrees C, pH 7.4 8.01), and a CO2 effect, independent of the pH Bohr effect, was measured at 5 degrees C. Hill coefficients varied widely (n50 = 0.95-3.95) and did not appear to vary with temperature or pH. The hemocyanin oxygen binding properties of B. thermydron blood are not affected by dialysis against salines having the same inorganic ion composition as the blood. Hemocyanin of dialyzed blood from A. lusca demonstrated a reverse temperature effect and a large Bohr effect (delta logP50/delta pH = -0.77 at 5 degrees C, pH 7.4-7.7). Functional aspects of oxygen binding are discussed in relation to the hydrothermal vent environment, and in the context of recent work on crustacean hemocyanins. PMID- 3340814 TI - Acute exposure to graded levels of hypoxia in rainbow trout (Salmo gairdneri): metabolic and respiratory adaptations. AB - We have studied the mechanisms of acute hypoxia tolerance in rainbow trout (Salmo gairdneri). Fish held at 9 degrees C were exposed to various levels of hypoxia for 24 h. At an environmental PO2 of 30 Torr, the fish showed an initial plasma acidosis probably of metabolic origin which was subsequently offset such that blood pH returned to normal within about 4 h. Over this time period, red cell pH was maintained constant. Comparing the effects of different levels of hypoxia following 24 h exposure, oxygen consumption of the animal remained unchanged over a broad range of inspired oxygen tensions but declined by over 30% of normoxic values at inspired water PO2 levels of 80 Torr. This appeared to be a true metabolic depression because signs of increased anaerobic metabolism did not occur until there was a further reduction in water oxygen levels. Rainbow trout appear to be able to maintain a relatively high energy status in their white muscle during 24 h exposure to severe hypoxia (water PO2 = 30 Torr). As the level of hypoxia was intensified, there was a reduction in the oxygen gradient across the gills, probably facilitated in part by the release of catecholamines into the blood. The erythrocytic ATP: Hb4 molar ratios declined with increasing hypoxic stress as did the pH gradient between the erythrocyte and plasma. The overall effect was no change in Hb O2-affinity after 24 h exposure to severe hypoxia. PMID- 3340815 TI - Analysis of intracardiac shunting in the lizard, Varanus niloticus: a new model based on blood oxygen levels and microsphere distribution. AB - The central sites of the cardiovascular system (right and left aortic arches, RAo and LAo, pulmonary artery, PA, and right and left atria, RAt and LAt) were chronically and non-occlusively cannulated for an analysis of intracardiac shunting in Varanus niloticus. Oxygen partial pressure (PO2) and oxygen concentration (CO2) were significantly higher in right aortic blood than values determined in left aortic blood. The difference was larger in animals acclimated to 25 degrees C (RAo CO2 = 4.5 +/- 1.00 vol %, LAo CO2 = 3.8 +/- 1.14, X +/- SD, n = 19) than at 35 degrees C (RAo CO2 = 5.8 +/- 1.24, LAo CO2 = 5.4 +/- 1.35, n = 18) (P less than 0.001 for both temperatures, paired t-test). These data are explained by a new model describing the differential shunting patterns of the two aortae in addition to the conventional overall right-to-left and left-to-right shunt fractions. This model was solved on the basis of blood gas data collected by simultaneous multiple-site gas analysis, together with data on the differential blood flow in the central vascular system, collected by application of the microsphere method. At 35 degrees C both right-to-left and left-to-right shunts were relatively small (about 9%), with the right-to-left shunt fraction directed exclusively into the left aorta. Thus right aortic blood represented left atrial blood, whereas left aortic blood was composed of 80% left atrial and 20% right atrial blood. Ninety percent of the pulmonary arterial blood was derived from the right atrium and 10% from the left atrium. At 25 degrees C the composition pattern of effluent blood for each vessel was similar, the absolute flow distribution, however, was different from that at 35 degrees C. These findings are discussed with respect to their significance and compatibility with the wash-out shunt model. PMID- 3340816 TI - Non-muscular factors in upper airway patency in the rabbit. AB - The hypothesis tested in these experiments was that factors other than contraction of upper airway muscles influence the resistance of the upper airway to collapse. The intra-luminal pressures required to close and re-open the upper airway were measured in the isolated upper airways of anesthetised rabbits. The level of activity in upper airway muscles manipulated by ventilation with 100% O2 or 7% CO2 and by muscle paralysis with gallamine. During ventilation with 100% O2 closing pressure was -10.34 +/- 0.53 cm H2O (mean +/- 95% c.i., n = 23) and re opening pressure was -3.15 +/- 0.51 cm H2O. Ventilation with 7% CO2 changed the closing pressure to -11.63 +/- 0.67 cm H2O (P less than 0.05) and re-opening pressure to -3.81 +/- 0.67 cm H2O (NS). In 10 animals muscle paralysis with gallamine (2 mg/kg i.v.) did not significantly alter closing or re-opening pressures during ventilation with 100% O2, and did not abolish the ability of ventilation with 7% CO2 to augment collapse resistance. In 6 animals death was followed by a fall in closing and re-opening pressures to 30-60% of the values recorded in paralysed animals. We conclude that in this preparation active muscle contraction is not the main source of resistance to airway closure or of the proclivity of the closed airway to re-open. PMID- 3340818 TI - Chemoreceptor stimulation interferes with regional hypoxic pulmonary vasoconstriction. AB - Hypoxemia interferes with the diversion of blood flow away from hypoxic regions of the lung, possibly through activation of the arterial chemoreceptor reflex. The purpose of this study was to determine if selective stimulation of carotid chemoreceptors reduces the diversion of flow (hypoxic vasoconstriction) when normal systemic oxygen levels are present. Chloralose anesthetized dogs were paralyzed and each lung was separately ventilated via a dual-lumen endobronchial tube. Left pulmonary artery (QL) and main pulmonary artery (QT) blood flows were measured with electromagnetic flow probes. Chemoreceptors were stimulated by perfusion of the carotid sinuses with hypoxic, hypercapnic blood. QL/QT averaged 46 +/- 4, 29 +/- 2, and 36 +/- 4% during bilateral O2 ventilation (control), left lung N2 ventilation, and left lung N2 plus chemoreceptor stimulation in dogs treated with the cyclo-oxygenase inhibitor meclofenamate. After vagotomy, QL/QT averaged 45 +/- 4, 27 +/- 3, and 28 +/- 2% during the same conditions. QL/QT decreased significantly from control (P less than 0.05) during left lung N2 alone but did not decrease during left lung N2 plus chemoreceptor stimulation in dogs with intact vagi. In contrast, QL/QT decreased significantly both before and during chemoreceptor stimulation in vagotomized dogs. The same responses were observed in dogs not treated with meclofenamate. These results indicate that selective stimulation of arterial chemoreceptors can interfere with regional hypoxic vasoconstriction and suggest that the vagus nerves may mediate this effect. PMID- 3340817 TI - Acid infusion elicits thromboxane A2-mediated effects on respiration and pulmonary hemodynamics in the cat. AB - We have recently reported that infusion of stoichiometrically equal quantities of acid and base (neutral acid-base infusion) in the cat resulted in rapid, shallow breathing and in pulmonary hypertension (Orr et al., 1987). To investigate the mechanisms involved in these effects, we have measured in the anesthetized cat thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1 alpha, the stable metabolites of TXA2 and PGI2, in blood as well as cardiorespiratory parameters in response to neutral acid-base infusion. The first acid-base infusion prompted right ventricular blood pressure (Prv) to rise from 30 to a peak of about 55 mm Hg, with a concomitant rise in the right ventricular TXB2 level from below detection level to over 500 pg/ml. The second or third infusion evoked no (or small) rises in Prv and TXB2, individual values of Prv and TXB2 being tightly correlated. After blockade of TX synthesis by Dazmegrel, no changes were observed even at the first acid-base infusion in either Prv or TXB2. The TXA2 mimetic, U 46,619, caused Prv to rise with no change in TXB2, and this effect was repeatable. Increases were also observed in ventilation, particularly in respiratory rate. We conclude that acid exposure of blood stimulates TX synthesis and release from platelets, which in turn leads to pulmonary hypertension and to hyperventilation. The fact that these effects cannot be repeated within the same animal is due to a lack in TX release but not to a loss of responsiveness of the TX receptors in the lung. PMID- 3340820 TI - The isolation of human lung mast cells by affinity chromatography. AB - A method of isolation has been developed to purify mast cells from human lung tissue. The purification steps are: (1) dispersion of human lung tissue in single cell suspensions by enzymatic digestion, (2) partial purification by counterflow centrifugal elutriation, (3) Percoll gradient centrifugation, and (4) enrichment of the mast cells by affinity chromatography using anti-human IgE-Sepharose. Enzymatic dispersion yielded 0.6 +/- 0.2 x 10(6) mast cells per gram wet tissue with purities of 3.3 +/- 1.0% (mean +/- SEM n = 3). Elutriation and gradient centrifugation yielded 0.36 +/- 0.05 x 10(6) mast cells per gram lung tissue in fractions with purities of 30.8 +/- 10.7%. Enriched mast cell fractions were combined, and disposed of contaminating cells by affinity chromatography, thereby yielding 0.25 +/- 0.03 x 10(6) mast cells per gram lung tissue, and improving the purity to 75.3 +/- 8.3%. The purified mast cells were intact and vitality exceeded 95%. In this way from 1 g wet lung tissue 0.25 +/- 0.03 x 10(6) mast cells may be isolated with a mean recovery of 41.7 +/- 2.4% and a mean purity of 75.3 +/- 8.3%. PMID- 3340819 TI - Vagal influences on parasternal intercostal muscle inspiratory shortening during hypercapnia and airway occlusion. AB - To determine whether increases in electromyographic activity (EMG) are necessary for respiratory muscle shortening to occur during airway occlusion, respiratory changes in parasternal intercostal muscle length were measured using sonomicrometry in 11 anesthetized dogs during unoccluded (UB) and occluded (OB) breaths before and after vagotomy. During UB the extent of parasternal intercostal inspiratory shortening was greater after than before vagotomy both during oxygen breathing and during progressive hyperoxic hypercapnia. The relation between parasternal shortening, parasternal EMG, and tidal volume was not substantially affected by vagotomy. During OB parasternal intercostal EMG increased significantly compared to UB when the vagi were intact, but airway occlusion did not significantly change EMG activity post-vagotomy. However, both before and after vagotomy the parasternal intercostal shortened during OB in all animals. Parasternal intercostal inspiratory shortening during OB as a % of that during UB was significantly greater before compared to after vagotomy during oxygen breathing and moderate hypercapnia, but vagal integrity made no significant difference at high CO2. These results suggest that (1) pulmonary stretch receptor afferents inhibit parasternal intercostal inspiratory shortening but in proportion to their inhibitory effects on parasternal intercostal EMG and tidal volume, and (2) even when the EMG stays constant the parasternal intercostal muscle does not contract isometrically during occluded breaths. PMID- 3340821 TI - A new prealbumin variant in familial amyloid cardiomyopathy of Danish origin. AB - A C-terminal fragment of a prealbumin variant was isolated from amyloid material obtained from the myocardium of a patient (Han) with familial amyloid cardiomyopathy of Danish origin. The prealbumin variant fragment was shown to have a methionine for leucine substitution in position 111. PMID- 3340822 TI - Post-translational processing of the murine third component of complement. AB - The biosynthesis and secretion of the third component of complement (C3) has been studied with the macrophage cell line J774.2. C3 is initially synthesized as a single polypeptide chain precursor termed pro-C3, of relative molecular weight (Mr) 170,000 that is post-translationally modified by proteolytic cleavage into two polypeptides linked by disulphide bonds. The larger polypeptide, termed the alpha chain, has an Mr of 110,000-115,000, while the smaller beta chain has an Mr of 55,000-60,000. Pulse-chase experiments indicate that the proteolytic processing of pro-C3 occurs intracellularly, just prior to secretion. Unlike human C3, which has carbohydrate on both the alpha and beta chains, only the alpha chain of murine C3 is glycosylated. The carboxylic ionophores monensin and nigericin totally inhibit the proteolytic processing of pro-C3 at a concentration of approximately 10(-6) M. This block on proteolytic processing was shown not to be mediated by changes in intracellular pH induced by the disruption of proton gradients. Rather, data from experiments using carboxylic ionophores and other perturbants of cellular physiology indicated that the enzyme(s) responsible for the proteolytic cleavage of pro-C3 either reside in a cellular compartment with a neutral pH or are proteinases active over a relatively broad pH range. PMID- 3340823 TI - Lymph-borne dendritic leucocytes do not recirculate, but enter the lymph node paracortex to become interdigitating cells. AB - Peripheral lymph contains constitutively major histocompatibility complex (MHC) class II-positive, dendritic leucocytes (DL) with a veiled (VC) or dendritic (DC) shape. On the basis of phenotypic similarities to the interdigitating cells (IDC) of T-dependent areas of lymphoid tissues, they are believed, but not yet proven, to be IDC precursors that develop into mature IDC within the draining lymph nodes. In order to determine the relationship between VC/DC and IDC, highly purified radiolabelled peripheral lymph DL (collected by thoracic duct cannulation of mesenteric lymphadenectomized congenitally athymic, nude rats) were reinjected into the veins or footpads of syngeneic recipients. Later, host blood and lymph were collected and the tissues were biopsied and processed for scintillation counting or for light microscopic autoradiography combined with electron microscopy of neighbouring sections. The intravenously injected VC/DC did not enter lymph nodes or Peyer's patches directly from blood and did not re enter the lamina propria of the gut, but became localized largely in the liver and the spleen. From the liver some of the cells proceeded via afferent lymphatics to the liver and the spleen. From the liver some of the cells proceeded via afferent lymphatics to the coeliac lymph nodes. Similarly, some of the locally injected cells were carried with peripheral lymph to the draining popliteal lymph nodes, although most were retained in the footpads. In the spleen the VC/DC entered the periarteriolar lymphoid sheaths and in the coeliac and popliteal lymph nodes they became localized in the paracortex, where they acquired the morphology of mature IDC. PMID- 3340824 TI - Detection of tumour necrosis factor from lipopolysaccharide-stimulated human mononuclear cells by enzyme-linked immunosorbent assay and cytotoxicity bioassay. AB - Tumour necrosis factor (TNF) or cachectin is an important mediator of endotoxic activity. To investigate the production of TNF from human mononuclear cells (MNC) in response to lipopolysaccharide (LPS), we developed a sensitive and specific enzyme immunoassay (ELISA) and a cytotoxicity bioassay for TNF. The ELISA utilizes the biotin/avidin system and includes four incubation steps. The detection limit was 25 pg recombinant TNF (rTNF)/100 microliter. There was no interference of medium, serum, plasma, spinal fluid, or urine and no cross reaction with natural or recombinant IL-1-alpha, IL-1-beta, IL-2, IFN-gamma, or lymphotoxin (TNF-beta). Recovery of TNF added to the media was 85-123% (n = 22). The relative standard deviations within and between assays were 7% and 8%, respectively. TNF-induced cytotoxicity was measured on actinomycin-D-treated L-M mouse fibroblasts. The detection limit in this bioassay was 0.5 U/30 microliter or 12.5 pg/30 microliter of rTNF. IL-1-alpha and IL-1-beta slightly inhibited the cytotoxic activity of rTNF. In this bioassay, cytotoxic activity (50-300 U/ml) was detected only when MNC were stimulated with high concentrations of LPS (100 1000 ng/ml). In contrast, using 0.01-100 ng/ml of LPS, the ELISA detected TNF in a dose-dependent manner (0.25 ng/ml to 40 ng/ml). It is concluded that TNF is liberated from human blood MNC if stimulated with minute amounts of LPS. It is suggested that human TNF may be secreted in a relatively inactive form or that inhibitors of TNF are generated along with the monokine. Because of this, and because commonly used bioassays for TNF fail to distinguish between TNF and lymphotoxin, specific ELISA are recommended to supplement TNF bioassays. PMID- 3340825 TI - A critical consideration of the rat epididymis as an immunologically privileged site. AB - A literature search reveals a lack of any previous attempt to implant foreign tissue into the epididymis. Instead, related studies have been carried out within the adjacent testis. Theoretically, there are peculiar immunobiological factors that can require separate consideration of the two adjacent sites. With this background, we designed the present work by removing the adjacent testis and subsequently used biochemical, histological, and electron microscopic methods to assess the fate of parathyroid allografts buried within the epididymis. Since the concept of immunological privilege is usually explained on the basis of the nature of lymphatic drainage, we also studied the pattern of lymphatic drainage at each allograft bed. In the analysis of our results, the animals were grouped according to the nature of lymph pattern from each transplant bed. We observed that prolonged survival of the tissue allograft occurred only when the lymphatic trunk draining the graft bed bypassed all retroperitoneal nodes and opened directly into the blood stream via the cisterna chyli. This anomalous survival is favoured by pretransplant splenectomy. These results demonstrate that the rat epididymis can sometimes be immunologically privileged. PMID- 3340826 TI - Aging-associated changes in murine intestinal immunoglobulin A and M secretions. AB - The aging effect on the quantity of intestinal IgA and IgM class-specific immunoglobulins secreted and the quality of intraluminal intestinal IgA was studied in 5- to 6-month-old and 24- to 28-month-old male BALB/c mice. The level of IgA increased in the intestinal juice from the aged mice, while the IgM level remained unchanged. These alterations were similar to those found in serum, but the effect of age on serum IgA was profound, almost a threefold increase, in contrast to an increase of just under 35% in intestinal secretions. The ratio of dimeric to total IgA in the small intestine decreased in the older mice, though that of serum was unchanged. In contrast, the total amounts of dimeric IgA in the small intestinal lavage fluid did not change between the two age groups, while the dimeric IgA in serum in older mice were 4.5 times as high as those of young mice. The binding of purified intestinal dimeric IgA to antigens from normal habitant enteric bacteria (gamma streptococci and Enterobacter agglomerans) declined in the old mice. In the immunochemical studies, using SDS-PAGE and isoelectric focusing, the purified intestinal IgA from the young and old mice showed no major differences. Thus, the findings in aged small intestinal perfusates that the increased content of intraluminal IgA is due to an increased monomeric IgA, but not to a reduced dimeric IgA, which remains unchanged, and that the binding capacity of the dimeric IgA to the bacterial antigens is diminished, suggest that the level of the natural secretory IgA antibody is decreased. These altered quantitative and functional features of intraluminal intestinal IgA observed in the aged mice appear to be due to the complex heterogeneous effects of senescence on gut-associated lymphoid tissues, and may contribute to age-related impairment in gut humoral immune function. PMID- 3340827 TI - The serum antibody response distributed in subclasses and isotypes after intranasal and subcutaneous immunization with influenza virus immunostimulating complexes. AB - Immunostimulating complexes (iscoms) were prepared from influenza virus glycoproteins (A/PR8(H1N1]. Mice were inoculated with iscoms by local (oral or intranasal) as well as by subcutaneous administration. It was shown that one subcutaneous or intranasal inoculation induced serum antibody responses of similar magnitude. The intranasal administration, however, induced somewhat higher IgA and IgM titres than that induced subcutaneously. After a second intranasal or subcutaneous inoculation a prominent increase of the IgG isotypes was found. The secondary IgA and IgM responses were of similar magnitude as those induced after the primary inoculation. The antibody responses induced were evenly distributed within the IgG isotypes, although the highest titres recorded were of the IgG1 and IgG2 isotypes. PMID- 3340828 TI - Proposition 65: implementation. PMID- 3340830 TI - Animal stealer convicted. PMID- 3340829 TI - J&J finds a place in the sun. PMID- 3340831 TI - IOM and Soviet Academy sign first exchange pact. PMID- 3340832 TI - An "intellectual summit". PMID- 3340833 TI - Cloning sheep and cattle embryos. PMID- 3340834 TI - Synthesizing a color algorithm from examples. AB - A lightness algorithm that separates surface reflectance from illumination in a Mondrian world is synthesized automatically from a set of examples, which consist of pairs of input (intensity signal) and desired output (surface reflectance) images. The algorithm, which resembles a new lightness algorithm recently proposed by Land, is approximately equivalent to filtering the image through a center-surround receptive field in individual chromatic channels. The synthesizing technique, optimal linear estimation, requires only one assumption, that the operator that transforms input into output is linear. This assumption is true for a certain class of early vision algorithms that may therefore be synthesized in a similar way from examples. Other methods of synthesizing algorithms from examples, or "learning," such as back-propagation, do not yield a significantly better lightness algorithm. PMID- 3340835 TI - Genomic amplification with transcript sequencing. AB - A sequencing method called genomic amplification with transcript sequencing (GAWTS) is described that is based on amplification with the polymerase chain reaction (PCR). GAWTS bypasses cloning and increases the rate of sequence acquisition by at least fivefold. The method involves the attachment of a phage promoter onto at least one of the PCR primers. The segments amplified by PCR are transcribed to further increase the signal and to provide an abundance of single stranded template for reverse transcriptase-mediated dideoxy sequencing. An end labeled reverse transcriptase primer complementary to the desired sequence generates the additional specificity required to generate unambiguous sequence data. GAWTS can be performed on as little as a nanogram of genomic DNA. The rate of GAWTS can be increased by coamplification and cotranscription of multiple regions as illustrated by two regions of the factor IX gene. Since GAWTS lends itself well to automation, further increases in the rate of sequence acquisition can be expected. PMID- 3340836 TI - The AIDS issue. PMID- 3340838 TI - Child care dilemma. PMID- 3340837 TI - Rinderpest campaign in Africa. PMID- 3340840 TI - Perot to fund scientist-physicians. PMID- 3340841 TI - Doctored report revives debate on 1957 mishap. PMID- 3340839 TI - Politics and Soviet psychiatry. PMID- 3340842 TI - Science lobbying groups formed. PMID- 3340843 TI - Molecular clocks turn a quarter century. PMID- 3340845 TI - Education to prevent AIDS: prospects and obstacles. AB - A number of obstacles thwart effective education to prevent AIDS in the United States. These include the biological basis and social complexity of the behaviors that must be changed, disagreement about the propriety of educational messages to prevent AIDS, uncertainty about the degree of risk to the majority of Americans, and dual messages of reassurance and alarm from responsible officials. Long-term protection of an individual from infection requires extreme changes in risk taking behavior. Partial shifts toward safer practices may be epidemiologically important in retarding the rate and extent of spread of infection. Though some striking changes in behavior have occurred, especially in homosexual populations in areas with high prevalence of AIDS, educational efforts to date have succeeded more in raising awareness and knowledge about AIDS than in producing sufficient changes in behavior. The United States has yet to mount a nationwide comprehensive, intensive, and targeted education program to prevent AIDS. PMID- 3340844 TI - Legal rights and duties in the AIDS epidemic. AB - This article provides an overview of some major areas of legal concern in which the AIDS epidemic is having an impact. The rights of infected individuals to testing, treatment, and confidentiality are reviewed, and emphasis is given to their claims to nondiscrimination regarding access to health care, employment, housing, education, insurance, and related interests. Infected persons' duties to contain transmission of AIDS are outlined under principles of criminal and civil law, including liability for provision of contaminated blood products. Uninfected people's general rights to protection are considered, and health professionals' and authorities' rights and duties are given more detailed attention. In conclusion, some legal developments outside the United States are reviewed. PMID- 3340846 TI - Ethical issues in the prevention and treatment of HIV infection and AIDS. AB - The epidemic of infection with the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS) poses a major ethical question: How can we control the epidemic and the harm that it causes without unjustly discriminating against particular social groups and without unnecessarily infringing on the freedom of individuals? This question pertains to three spheres of public policy in the United States: public health, the delivery of health care, and research. In the public health sphere, vigorous educational efforts will be required, as will modified approaches to intravenous drug use, prostitution, and homosexual and bisexual sexual activity. Carefully targeted, voluntary testing and screening programs should be coupled with counseling and with guarantees of confidentiality and nondiscrimination where these are appropriate. Both health care workers and the health care system have a moral obligation to provide care to people with HIV infection, but heroic self sacrifice should not be required provided that infection control precautions are observed. Patients with neurological involvement and terminally ill patients will benefit from statutes allowing recognition of advance directives about preferred modes of care or nontreatment. There is a moral imperative to perform intensive research directed toward the understanding, treatment, and prevention of HIV infection and AIDS. The research process will raise challenging ethical questions. PMID- 3340847 TI - Epidemiology of HIV infection and AIDS in the United States. AB - By the end of 1987, nearly 50,000 cases of acquired immunodeficiency syndrome (AIDS) had been reported since 1981, 20,745 in the past year alone. Black and Hispanic adults and children have reported rates 3 to 12 times as high as whites. This can be largely attributed to higher reported rates in black and Hispanic intravenous (IV) drug abusers, their sex partners, and infants. In 1986, reported AIDS deaths increased adult male and female mortality in the United States by an estimated 0.7 and 0.07%, respectively, with much greater increases in selected age groups or areas of the country. The greatest variation in infection with the human immunodeficiency virus (HIV) (0 to 70%) has been found in surveys of IV drug abusers, while surveys of homosexual men reveal infection rates of 20 to 50%. Infection with HIV ranged from 0 to 2.6% in limited sexually transmitted disease clinic surveys of heterosexual men and women without a history of IV drug abuse or known sexual contact with persons at increased risk. The modes of HIV transmission are now well understood, but a large amount of biologic variability in efficiency of transmission remains to be explained. The period between initial infection with HIV and the development of AIDS is variable, but the risk for disease progression increases with duration of infection. PMID- 3340848 TI - Cell-cell interactions in the guidance of late-developing neurons in Caenorhabditis elegans. AB - The initial outgrowth of developing neuronal processes can be affected by a number of extrinsic interactions. Cell-cell interactions are also important in a later stage of neuronal outgrowth when processes grow into the region of their targets. The correct positioning of the process of a postembryonic sensory neuron, the touch cell AVM of the nematode Caenorhabditis elegans, at its synaptic targets requires the presence of a pair of embryonic interneurons, the BDU cells. These cells receive synapses from AVM but do not participate in the touch reflex circuit. Therefore, the AVM-BDU synapses may be required to stabilize the association between these cells and assist in the guidance of the AVM processes through a mature neuropil. PMID- 3340850 TI - Brainwave counting. AB - Robert E. Ricklefs' name was misspelled throughout Roger Lewin's Research News artide "Egglaying" in birds remains a hot issue (29 Jan., p. 465). PMID- 3340851 TI - AIDS and drug abuse: no quick fix. PMID- 3340849 TI - Is ethanol antagonist Ro15-4513 selective for ethanol? PMID- 3340852 TI - Patent claim buildup haunts biotechnology. PMID- 3340853 TI - NIH scientists balk at random drug tests. PMID- 3340854 TI - Academy backs genome project. PMID- 3340855 TI - Causes of the liability insurance crisis. AB - In this article the reasons for recent dramatic premium increases for liability insurance are explored by examination of available data on industry premiums, losses, and expenses. The suggestions that the premium increases were primarily caused by collusion among insurers, cyclical behavior, or systematic errors in forecasting losses are rejected. Instead, the evidence indicates that the jump in liability insurance premiums is most plausibly due to the growth in the discounted value of expected liability losses. PMID- 3340856 TI - Glycosyl-phosphatidylinositol moiety that anchors Trypanosoma brucei variant surface glycoprotein to the membrane. AB - Two forms of protein-membrane anchor have been described for the externally disposed glycoproteins of eukaryotic plasma membranes; namely, the hydrophobic transmembrane polypeptide and the complex glycosylphosphatidylinositol (G-PI) moiety. The chemical structures of the major species of G-PI anchors found on a single variant surface glycoprotein (VSG) of the parasitic protozoan Trypanosoma brucei were determined by a combination of nuclear magnetic resonance spectroscopy, mass spectrometry, chemical modification, and exoglycosidase digestions. The G-PI anchor was found to be heterogeneous with respect to monosaccharide sequence, and several novel glycosidic linkages were present. The results are pertinent to the mechanism of the biosynthesis of G-PI anchors. PMID- 3340857 TI - Biologically effective ultraviolet radiation: surface measurements in the United States, 1974 to 1985. AB - Recent reports of stratospheric ozone depletion have prompted concerns about the levels of solar ultraviolet radiation that reach the earth's surface. Since 1974 a network of ground-level monitoring stations in the United States has tracked measurements of biologically effective ultraviolet radiation (UVB, 290 to 330 nanometers). The fact that no increases of UVB have been detected at ground levels from 1974 to 1985 suggests that meteorological, climatic, and environmental factors in the troposphere may play a greater role in attenuating UVB radiation than was previously suspected. PMID- 3340858 TI - Effect of neonatal handling on age-related impairments associated with the hippocampus. AB - In rats, an environmental manipulation occurring early in life resulted in changes in the adrenocortical axis that persisted throughout the entire life of the animals and attenuated certain deficits associated with aging. Rats handled during infancy had a permanent increase in concentrations of receptors for glucocorticoids in the hippocampus, a critical region in the negative-feedback inhibition of adrenocortical activity. Increased receptor concentrations led to greater hippocampal sensitivity to glucocorticoids and enhanced negative-feedback efficacy in the handled rats. Thus, at all ages tested, rats that were not handled secreted more glucocorticoids in response to stress than did handled rats. At later ages, nonhandled rats also showed elevated basal glucocorticoid levels, with the result that there was a greater cumulative exposure to glucocorticoids in nonhandled rats. Increased exposure to adrenal glucocorticoids can accelerate hippocampal neuron loss and cognitive impairments in aging. Hippocampal cell loss and pronounced spatial memory deficits emerged with age in the nonhandled rats, but were almost absent in the handled rats. Previous work showed that glucocorticoid hypersecretion, hippocampal neuron death, and cognitive impairments form a complex degenerative cascade of aging in the rat. The present study shows that a subtle manipulation early in life can retard the emergence of this cascade. PMID- 3340859 TI - A fossil reptile embryo from the Middle Triassic of the Alps. AB - The first nothosaur (Neusticosaurus sp.) embryo, one of the very few fossil embryos known, provides a rare glimpse at reproduction in extinct reptiles. The specimen from the southern Alpine Middle Triassic (about 230 million years ago) was recognized as an embryo in comparison with an exceptionally large and well understood sample of juvenile and sexed adult Neusticosaurus sp. The skeleton shows many embryonic features and may well be the smallest fossil reptile known (body length 51 millimeters). It reached only 22% of mean adult length whereas modern reptiles of this size do not hatch before they reach about 30% of mean adult length. The question of ovipary versus vivipary in pachypleurosaurs is discussed in light of the embryo. PMID- 3340860 TI - 1988 guide to biotechnology products and instruments. Guide to scientific instruments. PMID- 3340861 TI - Advances in optical, confocal, and electron microscopic imaging for biomedical researchers. PMID- 3340862 TI - The growing usefulness of high-performance liquid chromatography. PMID- 3340863 TI - Enabling the future. PMID- 3340864 TI - Red tape and Federal grants. PMID- 3340865 TI - Reuters to defy Journal embargo. PMID- 3340866 TI - "I swear by Apollo the physician...". PMID- 3340868 TI - Breast hamartoma: a mammographic diagnosis. AB - The mammographic appearance of breast hamartoma, a benign cause of a breast mass, is characteristic. We present four cases from the University of Virginia to review the mammographic, pathologic, and clinical features of this unusual entity. PMID- 3340867 TI - Dollars and cents: minicholecystectomy and early discharge. AB - We present minicholecystectomy as a means of cost containment and discharge from the hospital 24 to 48 hours later. Among 450 patients undergoing this form of cholecystectomy through a 4 cm incision, only 49 stayed longer than an average of 1.2 days; all of those patients had preexisting surgical problems, some of which were corrected concurrently. Forty-two patients were admitted on the morning of the day of operation and stayed an average of 1.07 days. The mortality was 1/450 (0.2%); the complication rate was 3.1%. We have found the shorter and earlier procedure an excellent and safe means of cost containment and recommend that earlier discharge be considered for other procedures as well. PMID- 3340869 TI - Fractures of the sacrum and sacroiliac joint: evaluation by computerized tomography with multiplanar reconstruction. AB - Conventional roentgenographic views of the pelvis provide inadequate assessment of complex bony trauma. Computerized tomography (CT) allows simpler patient positioning, more reliable detection of subtle fractures, better characterization of complex fractures, and detection of associated soft tissue and joint space abnormalities. The addition of multiplanar reconstructions (MPR) provides a better understanding of the pathoanatomy. The sacrum and the sacroiliac joint, traditionally problematic to image, are particularly well defined by CT/MPR. Subtle diastasis and intra-articular fragments are more reliably detected when the transaxial image is supplemented by coronal reconstructions. The degree of comminution and direction of fragment displacement are also best defined by coronal and sagittal formatting. Surgeons often find this protocol useful in preoperative assessment of extent and stability of fractures, and in planning conservative or surgical management. PMID- 3340870 TI - Continuous spinal blockade: an old technique revisited. AB - In this paper we describe a technique for continuous spinal anesthesia, first described at the turn of the 20th century and long thought to have become obsolete. We discuss reasons for discontinuance and neglect of the technique, as well as its indications, applications, and specific advantages, and we report a significant illustrative case. PMID- 3340872 TI - Recreational waterslide injuries. AB - Recreational waterslide facilities are a growing phenomenon in the United States, and injuries associated with their use are beginning to appear. Although there have been fatalities, the vast majority of injuries are minor, and occur over a large denominator of slide rides. The overall incidence of injuries is low, though the incidence varies from one facility to another. If safety practices and design features are implemented, waterslide use may become safer. Epidemiologic data will be required to clearly identify the optimal features of injury prevention. PMID- 3340871 TI - Brown recluse spider bites of the upper extremity. AB - Brown recluse spider bites may cause painful, necrotic, slow-healing wounds. When these bites involve the hand and upper extremity, they can also create severe functional deficits and long-term disability. We reviewed an 11-year experience with brown recluse bites to the hand and upper extremity. Data from patients (n = 31) indicated a 20% incidence of functional complications (n = 6) unless conservative wound management, dapsone, and antibiotics were used. Delayed surgical excision was preferable until wounds were free from active inflammation. Painful, recurrent wound breakdown and hand dysfunction were more common with early surgical excision. These complications were successfully treated with steroids, sympathetic blockade, and early aggressive physical therapy. PMID- 3340873 TI - Shunt surgery in Meniere's disease: a follow-up report. AB - Between December 1969 and May 1986, 140 patients were treated for Meniere's disease using the endolymphatic sac subarachnoid shunt. The technique and results are contrasted with an earlier report. The surgical technique described includes modifications of the originally described procedure. A microcomputer was used for the storage and manipulation of data based upon 1972 Academy criteria. Control of vertigo was accomplished in 83% of patients; 51% of patients were graded class A or B, according to the 1972 Academy criteria. No serious complications occurred. Problems included the potential for serious complications, the lack of specific criteria for patient selection, and the continued deterioration of hearing with the passage of time. Comparison of data with those presented in 1973 indicates a lower overall success rate, but continued success in the management of vertigo and imbalance. The endolymphatic sac subarachnoid shunt is worthy of consideration in the management of Meniere's disease when surgery is indicated and retention of hearing is desirable. PMID- 3340874 TI - Postpartum depression. AB - The occurrence of mood changes in the postpartum period is common. This presentation will discuss three cases of postpartum mood changes illustrating the "normal" changes, depression with suicidal ideation requiring brief hospitalization, and psychotic depression requiring intensive psychiatric treatment. PMID- 3340876 TI - Advance health care planning: taking a "medical future". AB - This article describes the living will and durable power of attorney as legal mechanisms for advance health care planning, and discusses the role of the physician in health care planning. The concept of a "medical future" is a new but not radically different device for furthering the objectives of advance health care planning. PMID- 3340875 TI - Pregnancy-induced hypertension without proteinuria: is it true preeclampsia? AB - A profile scoring system has recently been developed as a standardized method of early identification and severity assessment of pregnancy-induced hypertension (PIH). The purpose of this study is twofold: (1) to compare the PIH profile scores of patients demonstrating mild PIH without proteinuria with those of patients demonstrating mild PIH with proteinuria, and (2) to introduce the PIH profile graph as a standardized clinical assessment tool. Serial PIH profile data after 24 weeks' gestation from 46 term primigravid patients with mild PIH (group 1 = 19 patients without proteinuria; group 2 = 27 patients with proteinuria) were plotted on PIH profile graphs and compared. Profile scores from ten normotensive primigravidas at term served as controls. Serial profile scores for groups 1 and 2 showed similar patterns on the profile graph. Based on these data, we believe that PIH without proteinuria is clinically and biochemically a manifestation of true preeclampsia before the onset of proteinuria. Furthermore, the PIH profile graph allows one to identify subtle changes in the disorder and to anticipate the development of severe preeclampsia. PMID- 3340877 TI - Coombs'-negative spherocytic hemolytic anemia and severe necrotizing renal vasculitis. AB - Vasculitis may be complicated by either hypoproliferative or hemolytic anemias. We have described a patient with a Coombs'-negative spherocytic hemolytic anemia and severe necrotizing renal vasculitis, two disorders not having been previously linked. The disorders were temporally related and both responded to immunosuppressive therapy. The precise cause of the hemolytic anemia remains unknown. PMID- 3340878 TI - Choledochocele: a rare form of choledochal cyst. AB - Choledochocele is the least common form of cystic dilatation of the biliary tree. Whether this condition is a congenital abnormality or the result of inflammation at the papilla of Vater is not clear. In most cases, the clinical presentation is that of intermittent abdominal pain, nausea, and vomiting, with biliary colic and/or jaundice. As described in our case, choledochocele has characteristic radiologic features, but the lesion can be easily overlooked if one is not aware of its distinctive appearance. PMID- 3340879 TI - Gangrenous ligamentum teres hepatis causing acute abdominal symptoms. AB - This unusual case of a gangrenous round ligament manifested by acute abdominal symptoms underscores the importance of the recent radiologic descriptions of the round ligament in computerized tomography and ultrasonography. The cause of the gangrenous process in this case remains unresolved. PMID- 3340880 TI - Primary carcinoid tumor of the testis. AB - We have presented a case of primary testicular carcinoid in an otherwise asymptomatic 50-year-old white man treated by right orchiectomy; a postoperative abdominal CT scan was normal. Histologically and cytologically the tumor resembled carcinoids of midgut origin. Most primary testicular carcinoid tumors are not clinically functional, and thus the diagnosis is not suspected preoperatively. PMID- 3340882 TI - Proximal stapled esophagogastric anastomosis. PMID- 3340881 TI - Profound muscle weakness and hypokalemia due to clay ingestion. AB - We have presented the case of a 43-year-old woman with severe myositis due to clay ingestion and hypokalemia. EMG studies revealed a pattern consistent with myositis, and muscle biopsy showed a nonspecific diffuse myositis. The clay was shown to act as a potassium binder. With potassium replacement and discontinuance of clay ingestion, the symptoms and signs abated and laboratory values returned to normal. PMID- 3340883 TI - Serum bile acid levels in liver disease: is there a clinical application? PMID- 3340884 TI - Necrotizing enterocolitis associated with Clostridium paraputrificum septicemia. AB - A 38-year-old woman with chronic, noncyclic neutropenia had an episode of acute abdominal pain associated with clostridial septicemia. Clostridium paraputrificum was isolated from blood and peritoneal cultures. The pathogenic potential of C paraputrificum was established by surgical biopsy specimens which demonstrated necrotizing enterocolitis with the typical gram-positive rods. This report strengthens a recognized, established association between neutropenia and clostridial infection. PMID- 3340886 TI - Necrotizing fasciitis complicating appendicitis. PMID- 3340885 TI - Crohn's disease of the vulva. AB - We have reported a case of Crohn's disease of the vulva, an unusual manifestation of inflammatory bowel disease. The initial management of this condition should be medical, using antibiotics and established regimens to control gastrointestinal symptoms. Surgical therapy is appropriate when medical management fails, as it did in our patient. PMID- 3340887 TI - Rash from nicotine gum: nicotine as a hapten. PMID- 3340888 TI - Carpal tunnel syndrome. PMID- 3340889 TI - X-rays and stab wounds. PMID- 3340890 TI - Chronic pain and depression. PMID- 3340891 TI - Very low glucose concentrations in hypocellular malignant pleural effusions. PMID- 3340892 TI - Promoting urinary continence in the elderly. PMID- 3340893 TI - The relationship between alcohol consumption and coronary risk factors in the CORIS Study. AB - The cross-sectional relationship between reported alcohol consumption and coronary risk factors was investigated in the three-community Coronary Risk Factor Study (CORIS) population, consisting of 7,188 participants. Among drinkers of both sexes, the lowest level of systolic and diastolic blood pressure, serum cholesterol, tobacco use, body mass index, total daily energy expenditure, uric acid and Bortner score were found at the lower end of the alcohol consumption range. Non-drinkers had higher mean values for most of these risk factors than light drinkers. An increase in alcohol consumption was associated with a progressive increase in almost all the risk factors. Although men used more alcohol than women, at comparable alcohol consumption levels women generally had lower levels of risk factors than men. PMID- 3340894 TI - Suicide in Cape Town--is the challenge being met effectively? AB - This cross-sectional descriptive study of 161 suicide inquests in the Cape Town area during 1983 and 1984 includes demographic characteristics of the study population and factors assumed to have had a determining influence on the act of suicide. The most striking finding was a much higher suicide rate among whites (14/100,000) than among coloureds (3/100,000) or blacks (0.7/100,000). Possible reasons for this are discussed. Disparity in the availability or utilisation of psychiatric help by different ethnic groups is highlighted, as well as the fact that many of those who receive help are not dissuaded from suicide. PMID- 3340895 TI - Behavioural screening of 10- and 13-year-old pupils in selected schools in the Cape Peninsula. AB - The outcome of the behavioural screening of 10- and 13-year-old pupils in selected schools in the Cape Peninsula is reported and the implications discussed. According to parents' reports 21% of 10-year-old and 17.6% of 13-year old children met the criteria for behaviour disorder. The rates according to teachers' reports were 9.5% and 10.5% respectively. Behaviour disorder occurred with significantly greater frequency among boys, pupils older than the expected age for their standard, pupils with an intelligence quotient below 100, and pupils who had a learning disability. PMID- 3340896 TI - Provision of services for mentally handicapped children in the Witwatersrand area. AB - Childhood mental retardation is defined as significantly subaverage general intellectual functioning existing together with difficulty in adaptive behaviour, manifesting during the period from birth to 18 years. We addressed the issues of diagnosis, placement and management of the mentally handicapped child in the Witwatersrand area and surveyed facilities available for them. According to our calculations, facilities were adequate for 69.7% white, 26% Indian, 9.3% coloured and only 7.6% black children. Urgent attention must be given to providing more care for these children, especially those with profound mental retardation. A special class in a regular school is the most appropriate environment for the mildly to moderately retarded group. PMID- 3340897 TI - The problems of diagnosing iron deficiency. PMID- 3340898 TI - Western Cape local authority compliance with tuberculosis policy, 1984. AB - Local authority compliance with the national tuberculosis regimen in 1984 was examined in 29 of the 32 largest local authorities in the western Cape. The variability in management practices was especially evident with respect to children. The effects of the relative lack of uniformity and deviations from recommended policy need to be determined. PMID- 3340899 TI - Platelet parameters. Part I. Platelet counts and mean platelet volume in normal and pregnant subjects. AB - Platelet counts and mean platelet volume (MPV) were studied in 564 normal subjects and 297 pregnant women using a Coulter Model S-Plus electronic counter. The reproducibility of these measurements both intra- and inter-sample was documented. The mean platelet count in the normal group was 283 x 10(9)/l while the mean MPV was 9.32 fl. An inverse correlation between platelet volume and platelet number was documented (r = -0.38; P less than 0.0001). By interval analysis, this inverse relationship was shown to be non-linear. In the pregnant subjects there appeared to be a progressive decrease in platelet count with advancing gestation; this reached a significant level when the first and third trimesters were compared with each other (P less than 0.05). The MPV was unchanged. The fact that the platelet count decreased in proportion to the red cell count suggested that a common factor, such as haemodilution, was in part responsible. There was again an inverse relationship between MPV and platelet number (r = -0.39; P less than 0.0001) shown to be non-linear by interval analysis. PMID- 3340900 TI - Platelet parameters. Part II. Platelet volume-number relationships in various normal and disease states. AB - The relationship between mean platelet volume (MPV) and platelet count was evaluated in 259 patients with rheumatoid arthritis and 311 patients with various haematological disorders. Platelet volume-number relationships determined in a previous study on normal subjects were used as a reference range. There was a significant inverse relationship between MPV and platelet count in patients with rheumatoid arthritis (r = -0.49; P less than 0.0001), which by interval analysis was shown to be non-linear. In the patients with haematological disorders, the platelets were found to be disproportionately small for number in patients with aplastic anaemia, chemotherapy-induced marrow suppression and some cases of acute idiopathic thrombocytopenic purpura (ITP). In subjects with chronic ITP followed longitudinally, the inverse platelet volume-number relationship was retained. MPV was appropriate for platelet number in myelodysplastic syndromes, variable in iron deficiency anaemia and disproportionately large in myeloproliferative syndromes, most notably in agnogenic myeloid metaplasia. The observation that the MPV was disproportionately large in comparison with the platelet count was used in establishing the diagnosis of an hereditary giant platelet syndrome in a family of British origin. PMID- 3340901 TI - Synovial cyst--an unusual cause of nerve root compression. A case report. AB - An elderly woman presented with a tense, synovia-lined ganglion, associated with the left L3/L4 apophyseal joint, which protruded posteriorly and caudally through the joint capsule and extended anteriorly and cephally into the neural canal. The intraspinal extension produced a compression radiculopathy of the L3 nerve root. Removal of the cyst produced acute and dramatic alleviation of the symptoms. PMID- 3340902 TI - Multicentric reticulohistiocytosis in a black patient. A case report. PMID- 3340903 TI - Clinical regression of amyloid nephropathy in a patient with rheumatoid arthritis. A case report. AB - A 22-year-old woman with active seronegative rheumatoid arthritis responded to intramuscular gold but developed proteinuria which settled when this therapy was stopped. Proteinuria recurred after 2 weeks of penicillamine therapy but settled when this regimen was stopped. Six months later she developed a nephrotic syndrome and rectal and renal biopsies showed evidence of amyloidosis. She was treated with chlorambucil for 1 year and the disease activity was well controlled. There was regression of the nephrotic syndrome and her serum albumin and renal function are normal 6 years later. PMID- 3340904 TI - Temporomandibular joint ankylosis in rheumatoid arthritis. A case report. AB - Rheumatoid arthritis can result in ankylosis of the temporomandibular joint. The objectives of treatment are to maintain ascending mandibular ramus height, improve joint function and prevent occlusal-facial deformity. These are achieved by the use of a glenoid fossa-condylar total joint replacement prosthesis. PMID- 3340905 TI - Inappropriate treatment of cosmetic ochronosis with hydroquinone. PMID- 3340906 TI - Mumps--an unusual presentation. PMID- 3340907 TI - Measles outbreak at Baragwanath Hospital--a plea for action. PMID- 3340908 TI - Incidence and bedside diagnosis of haemodynamically significant right ventricular infarction. AB - The incidence, diagnosis and clinical course of haemodynamically significant right ventricular infarction (RVI) were assessed prospectively in 90 patients with their first acute inferior myocardial infarction. The haemodynamic criteria for RVI were defined as a mean right atrial pressure of 10 mmHg or more and a mean right atrial pressure equal to or greater than the mean pulmonary capillary wedge pressure. Twenty-six patients (29%) had haemodynamic evidence of RVI (group A) whereas 64 (71%) did not meet the criteria (group B). ST-segment elevation in lead V4R was observed in 25 patients (96%) with haemodynamic evidence of RVI and in 15 (23%) without (P less than 0.001). The jugular venous pressure (JVP) was found to be elevated in 24 of the 26 group A and in 7 of the 64 group B patients (P less than 0.001). Kussmaul's sign was present in 21 group A and 3 group B patients (P less than 0.001). Of the clinical signs, elevation of the JVP with clear lung fields on the chest radiograph had the best predictive value (92%) for haemodynamically significant RVI. The ECG was highly sensitive (96%) but less specific (77%) and had a low predictive value (63%) for haemodynamically significant RVI. Hypotension and complete atrioventricular block occurred more frequently in group A patients (P less than 0.001 and P less than 0.01 respectively). The hospital mortality rate was similar in both groups. PMID- 3340909 TI - Midazolam for induction of anaesthesia in patients with limited cardiac reserves. A comparison with etomidate. AB - The new water-soluble benzodiazepine, midazolam (Dormicum; Roche), was compared with etomidate as part of a balanced technique for induction of anaesthesia in 16 patients undergoing cardiac valve replacement. Monitoring revealed a significantly greater fall in blood pressure in patients receiving midazolam (reaching dangerous levels in 2 patients), which suggests that this agent is not suitable for induction of anaesthesia in haemodynamically compromised patients. PMID- 3340910 TI - Periventricular/intraventricular haemorrhage and umbilical cord clamping. Findings and hypothesis. AB - The timing of umbilical cord clamping in 38 women with preterm labour was randomly assigned. Ultrasonographic evidence of periventricular/intraventricular haemorrhage (PVH/IVH), assessed blindly, was found in 77% of the group clamped early compared with 35% of those in whom clamping of the cord was delayed for 1 minute. A hypothesis to explain the possible contribution of the haemodynamic events which accompany cord clamping to the development of PVH/IVH is presented. PMID- 3340911 TI - Reduction of shoulder dislocations by the hanging method. AB - Over a 2-year period, 23 cases of anterior dislocation of the shoulder were managed by the hanging method, combined with a supraclavicular block. Reduction was easily accomplished in all but 2 of these cases. The technique is described. PMID- 3340912 TI - The value of magnetic resonance imaging in multiple sclerosis in South African born patients. AB - The results of magnetic resonance imaging (MRI) in supporting the diagnosis of multiple sclerosis in 24 South African-born white patients were studied. MRI confirmed the diagnosis in 87.5% of cases. It appears that MRI is useful in strengthening the diagnosis of multiple sclerosis in patients with clinically established disease. This study supports the validity of the clinical diagnosis of multiple sclerosis in South African patients and stresses the need for re evaluation of the incidence and prevalence of multiple sclerosis in this country. PMID- 3340913 TI - Haemoglobin estimation--reliability of the copper sulphate specific gravity v. the cyanmethaemoglobin colorimetric method. AB - Automated colorimetric and copper sulphate (4 solutions with different specific gravities) methods were used to examine 218 blood specimens. The correlation between the two was high (r = 0.82)--proving that the copper sulphate method is reliable for haemoglobin screening. Copper sulphate gives better results in the higher haemoglobin region, which includes the majority of healthy people. In the lower haemoglobin region this method generally gives lower results than the cyanmethaemoglobin method. Copper sulphate is also by far the cheapest means currently available for mass screening. PMID- 3340914 TI - Determination of the relationships between psychological stress levels and blood pressure, pulse and respiratory rates, weight and cigarette consumption. AB - Stress has often been invoked as the intervening variable between various patterns of environmental and psychological stimulation, and various physiological and non-physiological responses. In an attempt to document this, 71 subjects completed the Staats Stress-Vector Analysis Questionnaire yielding measures on environmental, psychogenic and somatogenic stress dimensions, as well as on an overall net stress measure. These were then correlated against the blood pressure, pulse rate, respiratory rate, weight and smoking indices of the respondents, measured under controlled circumstances. No linear correlation was apparent. The respiratory rate tended to be raised in the environmentally and overall stressed individuals as a class, while similar findings relating to weight and pulse rate applied to the psychologically stressed. Reasons are extended for these findings. PMID- 3340915 TI - Whither school health services for lower primary schoolchildren in Soweto? AB - Over 1,000 clinical examinations and screening procedures in Soweto lower primary schoolchildren revealed few significant health problems which had not previously been identified. Information from parents and teachers was of limited value. The study revealed that only a small percentage of children referred for further medical attention attended for investigation or treatment as advised. Most of the health problems found could well have been managed at a school-based primary care level. It would thus be desirable to modify and extend the role and functions of the school nurse. However, the effectiveness of so doing would depend on adequate training, the availability of personnel and the organisational structure of health care services. PMID- 3340916 TI - Cost analysis study of an in vitro fertilisation programme. AB - In vitro fertilisation (IVF) and embryo transfer has established itself as a modality in the treatment of infertile patients. Estimates of the cost of this relatively new procedure were investigated with specific assumptions. The maximum cost per (first) cycle totalled R1611.16. Laboratory expenses were the single most expensive entity, accounting for 39.2% of the total cost. Patient contribution was established at 32.6% of total cost and the approximate breakdown of cost for an IVF and embryo transfer programme for a university-based unit is given. PMID- 3340917 TI - Vertebral osteomyelitis after a closed fracture of the spine. A case report. AB - A case of spinal tuberculosis after a closed fracture, differing from the usual tuberculous spondylitis in that trauma appeared to have predisposed the affected vertebrae to haematogenous infection, is described. PMID- 3340918 TI - Small-bowel obstruction in pregnancy after Scopinaro weight reduction operation. A case report. AB - A case of small-bowel volvulus occurring during pregnancy after pancreaticobiliary bypass for morbid obesity is presented. The association between pregnancy, previous small-bowel bypass surgery and intestinal volvulus is discussed. PMID- 3340919 TI - Accelerated silicosis in a foundry shotblaster. A case report. AB - A case of accelerated silicosis in a shotblaster in an iron foundry is described. The clinical course was notable for the rapid progression of cor pulmonale and the appearance of clubbing over a period of 2-3 months. Radiographic and pathological features atypical of the more chronic forms of the disease are described. The importance of the occupational history and the need for the strictest respiratory protection in such work are illustrated. Stringent control of this type of operation is urgently needed. PMID- 3340920 TI - Two black South Africans with AIDS. PMID- 3340922 TI - Placebo--drug or non-drug? PMID- 3340921 TI - Neonatal apnoea due to proprietary medicines--still a problem. PMID- 3340923 TI - Prevention of unexplained stillbirth. PMID- 3340924 TI - Continuous morphine infusion for postoperative pain in children. PMID- 3340925 TI - Malaria--an increasing threat. PMID- 3340926 TI - Strategies for reducing aminoglycoside toxicity. PMID- 3340927 TI - Community-acquired pneumonia--factors influencing intensive care admission. AB - The mortality rate in critically ill patients with pneumonia who require invasive vital organ support, including mechanical ventilation, in an intensive care unit (ICU) remains above 50%. The contribution of these costly life support systems to the survival of patients with extensive pneumonia is a matter for debate. The high mortality rate in this group of patients can be attributed in part to the fact that they are frequently referred for ICU care when their condition has already deteriorated to the point of no return. A retrospective study over 18 months of 34 cases of community-acquired pneumonia (17 patients required ventilatory support in the respiratory ICU) was undertaken to identify criteria which would justify early admission to an ICU. These were first-line clinical and biochemical factors, three of which were present in all patients on admission to hospital: (i) bronchopneumonia or lobar pneumonia involving more than two lobes (P less than 0.001); (ii) respiratory rate greater than 30/min (P less than 0.001); and (iii) partial arterial oxygen pressure less than 8 kPa (P less than 0.001). Other systemic factors associated with a poor prognosis and admission to the ICU were clinical signs of septicaemia, abnormal liver function and low serum albumin value. A scoring system for severity of pneumonia based on these factors is proposed. The possibility of an improved prognosis in a potentially reversible disease can become a reality if this approach is employed prospectively. PMID- 3340929 TI - Train accidents and orthopaedic morbidity. The Groote Schuur Hospital experience. AB - The Department of Orthopaedic Surgery at Groote Schuur Hospital, Cape Town, treats a disturbingly large number of train-associated injuries. The magnitude of the problem, the associated high morbidity and the serious socio-economic implications are outlined. PMID- 3340928 TI - Enteropathogens associated with acute infantile diarrhoea in Cape Town. AB - The results of a year-long controlled study on the causation of acute infectious diarrhoea in infants are reported. Campylobacter fetus subspecies jejuni, rotavirus and certain enteropathogenic Escherichia coli (EPEC) types were identified as the most common enteropathogens. Shigella, Salmonella group B and Yersinia enterocolitica were significant but less common pathogens. Campylobacter, rotavirus, the significant EPEC types and Shigella infections were more frequent in the warm summer and autumn months. This only partially accounts for the marked summer peak of diarrhoea, since at this time the percentage of cases of undetermined causation is highest (61%). Over the year an identifiable cause of the diarrhoea was found in 49% of the patients studied. A specific EPEC type, 0126:K71(B16), appeared to vary in pathogenicity on a seasonal basis. Multiple enteropathogens occurred relatively frequently. PMID- 3340930 TI - Long-term results of Charnley low-friction arthroplasty of the hip. AB - The long-term results of 73 Charnley low-friction arthroplasties with follow-up of 10-14 years are presented. Eight hips required revision for socket migration resulting from excessive medialisation of the cup (2, 2.7%); breakage of the femoral stem (5, 6.8%); and loosening (1). A further 5 hips had radiological changes suggesting that they would require revision in the foreseeable future. Sixty hips (82.2%) remained clinically excellent with minimal radiological changes. PMID- 3340931 TI - A disproportionately high incidence of symptomatic coarctation of the aorta in white infants in the Transvaal. AB - A retrospective study of Johannesburg Hospital records revealed that during a 4 year period (1978-1981) 49 infants who had been born in the Transvaal had presented with symptomatic coarctation of the aorta in the first year of life. The total number of live births for this period was 92,697. This incidence of 0.529 new cases per 1,000 live births, or 1/1,892 births, is three times higher than that observed in a careful study in the USA. The age at presentation and sex ratio were similar to other reported series. There was no definite seasonal incidence. Two of the patients had siblings with coarctation of the aorta. The exact reasons for the unusually high number of cases which occurred in the years 1979 and 1981 (1/1,405 and 1/1,241 live births respectively) could not be determined. It is suggested that it is probably due to a combination of genetic predisposition and as yet unidentified environmental factors. PMID- 3340933 TI - Nutrition and cancer. PMID- 3340932 TI - Brenner tumours--a clinicopathological study. AB - In a clinicopathological study of 70 Brenner tumours in 61 patients seen at Groote Schuur Hospital during the 30-year period 1956-1985, 68 were benign, 1 malignant and 1 proliferating. Fifty-seven were pure tumours and the remainder were mixed with other ovarian neoplasms. The age range of patients was 26-71 years (median 49 years). Most of the Brenner tumours were incidental findings and probably not responsible for the symptoms or signs, which were most commonly a pelvic mass (28 patients) and abnormal vaginal bleeding (15). PMID- 3340934 TI - Cystic fibrosis in Cape Town. AB - A retrospective study of all patients with cystic fibrosis (CF) seen at the Red Cross War Memorial Children's Hospital was undertaken. A total of 106 patients were identified and of these 64 still attend the CF clinic regularly. By 1 year of age 95% had symptoms but only 63% had been correctly diagnosed. In 27% the diagnosis was only made after 5 years of age. Chronic lung disease, failure to thrive, and diarrhoea or steatorrhoea were the most common presenting symptoms. Clinical scores of those still attending the clinic show that 79% are in the mild or better categories. The overall mortality rate was 21% and death was due to severe chest disease in the vast majority of cases. On the basis of the number of new patients with CF born during a 4-year period and the total number of live births recorded in this time, the calculated incidence of CF in Cape Town was 1/2,000 for whites and 1/12,000 for coloureds. Calculated prevalence rates for both whites and coloureds were much higher in urban Cape Town than in the rural areas of the western Cape. This suggests that many cases remain undiagnosed in the rural areas. PMID- 3340935 TI - Allergic asthma in different population groups in the western Cape. Causative and complicating factors. AB - Allergic asthma is a disease with a well-defined aetiology, the recognition and elimination of which could be achieved with relatively simple and inexpensive prophylactic treatment. Some of the well-known factors--respiratory tract infections, exposure to cigarette smoke, specific antigens and regular application of prophylactic treatment--which could cause or complicate asthma were studied in groups of white and coloured patients. More respiratory tract infections occurred in coloured patients and they were more exposed to their own and secondary cigarette smoke. Pets and grass pollen allergenicity was more common among whites while allergy to Aspergillus fumigatus and Ascaris lumbricoides was found more frequently among coloured patients. Both white and coloured patients had problems with regular prophylactic control of their symptoms with inhaled beta-stimulants, even after an average of two education sessions per patient, but this was of greater dimension for the coloured (60%) than the white group (27%) (P less than 0.001). It is not possible to separate causative from genetic factors when studying asthma in different population groups, but recognition of prevailing causative factors for each group could stimulate an educational approach aimed at control by prevention rather than treatment of acute attacks. PMID- 3340936 TI - Rheumatic fever in an urban community. AB - Forty-six children with acute rheumatic fever were admitted to Coronation Hospital, Johannesburg, between April 1981 and December 1984; 4 of them were admitted twice during this period. Their ages ranged from 4.5 years to 12.4 years. Carditis was present in 26 patients, arthritis in 22, chorea in 14, subcutaneous nodules in 3 and erythema marginatum in 2. Three patients died and a further 3 had to undergo emergency valve replacement for intractable cardiac failure. Thirty-five developed rheumatic heart disease; they all had mitral regurgitation. Compliance with prophylaxis was acceptable in only 22 cases. PMID- 3340937 TI - Rectal examination in the detection of prostatic cancer. AB - Since the aetiology of prostatic cancer is unknown, and therapy for metastatic disease non-curative, a decrease in the mortality rate from this condition can only be achieved by early diagnosis and effective treatment of the primary tumour. For diagnosis of localised cancer no practical alternative exists to rectal palpation. Of 629 cases of prostatic cancer seen at Tygerberg Hospital, the disease had metastasised in 29% of white and 58% of coloured patients at initial diagnosis. Prostatism or urinary retention was the presenting complaint in 74.7% of patients. The letters of referral of 97 patients were examined to determine whether prostatic cancer had been diagnosed by the primary care physician before referral. Rectal examination by the referring physician was recorded or implied in 64.9% of patients, and in those patients who underwent rectal examination before referral prostatic cancer was diagnosed in 54%. These findings imply that the opportunity for early diagnosis of prostatic cancer may be missed in many patients in whom rectal examination by the primary physician is indicated. PMID- 3340938 TI - Non-gynaecological metastases to the vulva and vagina. AB - A retrospective study of 1513 vulval and vaginal biopsy specimens was undertaken to determine the frequency of non-gynaecological metastases to the vulva and the vagina; 7 cases were found. These were reviewed and an attempt was made to determine the mode of spread. PMID- 3340939 TI - Zinc nutriture in pregnant and lactating women in different population groups. AB - Zinc concentrations in plasma and milk of white, Indian and coloured pregnant and lactating women residing in the Pietermaritzburg area were determined. In all groups pregnant women were found to have lower plasma zinc concentrations than nonpregnant or lactating women; the depressed levels persisted for the first 5 days after parturition, whereafter they increased to normal values. Pregnant Indian and coloured women were found to have significantly lower plasma zinc levels than white women. Lactating Indian women also had lower zinc concentrations in both plasma and milk than white women. The possible detrimental effect of suboptimal zinc nutriture during pregnancy and lactation is discussed and a more extensive analysis of zinc levels during these periods is suggested. PMID- 3340940 TI - Reference concentrations of serum selenium and manganese in healthy nulliparas. AB - Reference serum selenium and manganese concentrations were established for healthy nulliparas aged 18-23 years resident in Cape Town. Measurements were determined for selenium in 100 female students who had been taking low-dosage triphasic contraceptive medication for a minimum of 3 months and in 100 female students who were not on contraceptive therapy. Manganese concentrations were determined for 25 female students from each group. The mean serum selenium concentrations were 0.988 +/- 0.189 micrograms/l (78 +/- 15 micrograms/dl) and 0.925 +/- 0.177 mumol/l (73 +/- 14 micrograms/l) respectively for females taking and not taking oral contraceptives. The corresponding concentrations for manganese were 21.84 +/- 9.82 nmol/l (1.20 +/- 0.54 micrograms/l) and 21.66 +/- 7.64 nmol/l (1.19 +/- 0.42 micrograms/l) respectively. The differences in selenium were statistically significant (P = 0.0231) but not for manganese (P = 0.910). PMID- 3340941 TI - Morbidity patterns from general practice in Cape Town. A pilot study. AB - A pilot survey of morbidity patterns reflected in general practice was undertaken by a panel of physicians in Cape Town during 1984-1985. Acute upper respiratory tract infections, bronchitis and bronchiolitis were the commonest reasons for contact. A definite pattern of contacts by day of week was noted. The age distribution of the contacts closely matched that of the suburb in which the practice was situated. PMID- 3340943 TI - Significance of bradycardia during antenatal fetal heart rate monitoring. AB - All antenatal fetal heart-rates recorded over 15 months were examined for moderate basal bradycardia (100-120/min). There were 5,644 tests in 3,894 fetuses of which 104 (2.7%) demonstrated bradycardia. This study group was then compared with a randomly selected control group. Fetal outcome (measured by intra-uterine death, number of fetal movements, 5-minute Apgar score and birth weight for gestational age) was similar for the study and control groups. Moderate fetal bradycardia does not seem therefore to indicate fetal jeopardy and delivery for this reason per se is probably unjustified. To avoid unnecessary interference for fetal distress, the range of the normal heart rate should be extended and 100 120/min included as normal. PMID- 3340942 TI - Comparison between a low-osmolar ionic (ioxaglate) and a low-osmolar non-ionic (iopamidol) contrast agent in cardiac imaging. AB - The aim of this study was to compare the subjective, haemodynamic and electrocardiographic changes associated with a low-osmolar ionic (ioxaglate) and a low-osmolar non-ionic (iopamidol) injection during routine ventriculography and coronary angiography. The double-blind study was terminated when 120 patients had been randomised to either ioxaglate or iopamidol. More patients (9) experienced nausea with ioxaglate than with iopamidol (2). One patient in each group developed urticaria during and immediately after the procedure. No patient in any group developed serious arrhythmias during dye injection. After left ventriculography the mean left ventricular end-diastolic pressure (LVEDP) increased significantly in the iopamidol group (P less than 0.001). The difference in the rise of LVEDP in the two groups was not significant. In both groups the systolic arterial pressure fell transiently after left ventriculography (P less than 0.001). The difference in the mean fall of the pressure was not significant. There was no significant change in heart rate with either left ventricular or selective right and left coronary artery injections in any of the groups. In the ioxaglate group with both right and left coronary artery injection, the mean QRS duration, mean Q-T interval and T-wave amplitude changed significantly (P less than 0.001). In the iopamidol group the QRS duration and Q-T interval were prolonged significantly only with left coronary artery injection (P less than 0.001). In all parameters no significant differences were noted in the two groups; only minor differences in the effects caused by the two contrast agents could be demonstrated. PMID- 3340945 TI - Echophonocardiographic estimation of pulmonary capillary pressure in acute myocardial infarction. AB - Non-invasive estimation of pulmonary capillary wedge (PCW) pressure by an echophonocardiographic technique is reported. The ratio of time interval from the Q-wave to the C-point (echocardiogram) (Q-C) and from aortic closing (A2) to the E-point (A2-E) correlated well with the measured PCW pressure (r = 0.89; P = 0.001). When these two intervals were subtracted (A2-E)-(Q-C) the correlation was r = -0.90 (P = 0.001). PMID- 3340944 TI - Barton's forceps deliveries at Paarl Hospital. AB - Experience in using Barton's forceps for mid-pelvic arrest of the fetal head in 348 cases has proved that this instrument is both easy to apply and safe for the baby, provided rigid adherence to safety criteria are observed. As modern obstetric practice is favourably disposed towards mid-pelvic forceps vaginal delivery, the particular advantages of Barton's forceps should be more widely extolled. Their use is an invaluable addition to the obstetrician's armamentarium. Training in their use should, however, be thorough and extensive and under the guidance of a skilled senior obstetrician. PMID- 3340946 TI - The regional obstetrician--an alternative model. AB - The concept of the 'regional obstetrician' is defined as an alternative role model for an obstetrician and gynaecologist working in an obstetric base hospital in a small town or rural area. The results of the implementation of this role model in the area served by Eshowe Hospital in Zululand are described. Overall perinatal mortality for all the institutions in the region dropped from 49.9/1,000 to 34.9/1,000 over a period of 3 years. A plea is made for the identification of all rural hospitals which function as base hospitals, and for the co-operation of the health authorities in each region served by such hospitals in the appointment of regional obstetricians to co-ordinate and develop the obstetric services in these regions. PMID- 3340948 TI - Infective endocarditis in pregnancy. A report of 3 cases. AB - Three pregnant patients with infective endocarditis presented with haematuria. The importance of this symptom is stressed and a brief review of immune-complex glomerulonephritis is given. The role of antibiotic therapy in preventing infective endocarditis is discussed. PMID- 3340947 TI - Bacterial aneurysm of the intracavernous carotid artery secondary to suppurative otitis media. A case report. AB - A case of an intracavernous carotid aneurysm, with ophthalmoplegia, secondary to cavernous sinus thrombophlebitis is reported. The necessity of angiography when this condition persists despite adequate antibiotic therapy is stressed. PMID- 3340949 TI - Caecal volvulus in pregnancy. A case report. PMID- 3340950 TI - Conditions at Baragwanath Hospital. PMID- 3340951 TI - Congenital left ventricular aneurysm presenting as an inferior myocardial infarction. PMID- 3340952 TI - Chediak-Higashi syndrome in a black child. PMID- 3340953 TI - Strabismus treatment--a referral dilemma. PMID- 3340954 TI - 'White lung' in a four month old infant. PMID- 3340955 TI - Virus-like structures in human stool. PMID- 3340956 TI - Indomethacin-induced renal failure. PMID- 3340957 TI - Strengthening the practice of epidemiology in southern Africa. PMID- 3340958 TI - Dangers of large doses of vitamin A during pregnancy. PMID- 3340959 TI - [Perinatal deaths in the rural areas of the Cape Province, January--December 1985]. AB - In this study 18 rural hospitals in the Cape Province were prospectively surveyed in respect of the number of deliveries, perinatal deaths, low-birth-weight babies, and the hospital facilities available for routine antenatal, intrapartum and neonatal care. During the study period (1 January - 31 December 1985) there were a total of 19,274 deliveries (birth weight greater than or equal to 1,000 g). The mean perinatal mortality rate was 27,3/1,000 deliveries (range 15.3 45.3). The prevalence of low-birth-weight babies ranged from 13.3% to 34.4% with a mean of 17.7%. By plotting the perinatal mortality rate against the prevalence of low-birth-weight babies a perinatal care index was established. A low perinatal mortality coupled with a high prevalence of low-birth-weight infants, for example, signifies proper care. The perinatal index was then used to compare the neonatal outcome of different hospitals. Outcome varied considerably, as did facilities and care. Serological tests for syphilis and blood groups were not known in the majority of patients at 4 hospitals involving 2,387 deliveries. No cervical cytology was done at 6 hospitals involving 5,462 deliveries. One hospital had no neonatal resuscitation equipment. There were no facilities for serum bilirubin measurements at 10 hospitals involving 8,867 deliveries. However, most problems identified are easily and cheaply rectifiable. PMID- 3340960 TI - Intestinal parasites in novice black miners. Prevalence and possible effect on heat acclimatization. AB - A study of 189 black novice miners at two goldmines showed: (i) an overall prevalence of parasites of 62%; (ii) that parasitization has no significant effect on physical fitness or the ability to acclimatize to heat; (iii) that parasitization does not appear to predispose to more frequent consultations at the mine dressing-stations; and (iv) that haemoglobin, although showing regional variation, was unaffected by parasite status, but eosinophil counts did show significant differences. PMID- 3340962 TI - Community-orientated primary health care. The responsibility of the team for the health of the total population. AB - Community-orientated primary health care (COPHC) is presented as a framework for the delivery of primary health care based on the epidemiologically assessed needs of the population. It requires that the health team and the responsible agencies or institutions take upon themselves responsibility for the provision of care in relation to these measured needs of all those persons entitled to the service. This epidemiological diagnosis of community health conditions will include both the measurement of the distribution of health and disease states in the community as well as the possible causes for this distribution--this is in order to plan possible intervention adequately. It is concluded that COPHC is to the advantage of the community, the health team and the health care system. PMID- 3340961 TI - Variations in the fluoride levels of drinking water in South Africa. Implications for fluoride supplementation. AB - The range of fluoride levels in the drinking-water of cities and villages in South Africa was determined during the transition from a very dry (1983) to a wet (1984/85) period. The combination fluoride ion selective electrode was employed for the determination of the fluoride concentration. It was found that fluoride levels in drinking-water changed for 93% of the cities and villages studied during the period 1983-1985. Furthermore, it became clear that when the water volume of the supplying source increased, the fluoride level decreased significantly (P less than 0.01). Boreholes showed significantly higher fluoride levels (P less than 0.01) than rivers or dams. The impact of the variation in drinking-water fluoride concentrations on supplementary fluoride dosage is discussed and recommendations made. PMID- 3340963 TI - The spatial distribution of infant mortality rates in South Africa, 1982. AB - Infant mortality rates (IMRs) systematically calculated for the statistical regions of South Africa are presented for those groups of the population for which birth and death data are routinely collected. The geographical variation in the IMR and its statistical significance is presented in a series of maps. A more detailed analysis is also provided for the larger metropolitan areas. PMID- 3340964 TI - Characteristics of infant mortality in the RSA 1929-1983. Part I. Components of the white and coloured infant mortality rate. AB - Secular trends in white and coloured neonatal, post-neonatal and infant mortality rates are presented for the period 1929-1983. More detailed information is given for deaths in the first month of life. During this 54-year period the infant mortality rate for whites has declined from 64.2/1,000 to 13.5/1,000, whereas the rate for coloureds fell from 158.8 (1938) to 55.0/1,000. The greater part of the latter decline occurred after 1970. Since 1945 the neonatal mortality rate (NMR) for whites has exceeded the post-neonatal mortality rate (PNMR) but among coloureds the PNMR still exceeds the NMR. PMID- 3340965 TI - Characteristics of infant mortality in the RSA 1929-1983. Part II. Causes of death among white and coloured infants. AB - The relative contribution of different causes of death in the first year of life is presented for the period 1929-1983. Infections and perinatal and respiratory causes most commonly result in infant death among coloureds, while perinatal and congenital causes are commonest among whites. Over the 54-year period studied the mortality rate due to infections has fallen dramatically among whites but much less so among coloureds. The two causes of death for which the ratios of coloured to white mortality are highest, viz. infections (28 times) and respiratory causes (9 times), are those which have the greatest post-neonatal mortality component. PMID- 3340966 TI - Infant mortality rates in urban areas of South Africa, 1981-1985. AB - National infant mortality rates (IMRs) for South Africa are at present based on guestimates. There is no reliable national black IMR estimate. A study was undertaken to determine the IMR for 10 large urban areas (where records are available) for 1981-1985 and to use these to estimate a national black IMR. Considerable variability in the IMR was found for blacks both between cities and years. An overall national IMR estimate for blacks of between 94 and 124 deaths per thousand live births was obtained. This is about twice as high as the national figure of 51.9 for coloureds. The coloured non-urban rate was 2.6 times the urban rate of 25.9 while the Asian and white rates were similar in urban and non-urban areas (17.9 and 12.3 respectively). PMID- 3340967 TI - Effect of the legislative definition of the terms 'stillborn' and 'viable'. A medicolegal impasse. AB - Like so many other medicolegal issues, the legal procedure and legal consequences when a child is stillborn may seem simple and straightforward. However, in practice this is anything but the case. The legislative definitions of the terms 'stillborn' and 'viable' cause inordinate problems. Various legal, medical and social difficulties will only be obviated by amendment of the legal definitions of these terms--a task which should be initiated by the medical and nursing professions. PMID- 3340968 TI - Cardiac dysfunction in primary hypoparathyroidism. A report of 3 cases. AB - During 1981 - 1986 3 women with similar complaints were seen. Their symptoms were tetany and congestive cardiac failure (CCF) without a previous history of cardiac disease or alcohol abuse. One patient did have a history of cataract removal and epilepsy and all 3 had ECGs showing prolonged Q-T intervals and echocardiograms consistent with the diagnosis of cardiomyopathy. Biochemical profiles were similar: hypocalcaemia, hyperphosphataemia and normal serum urea levels. Parathyroid hormone levels were inappropriately low in all 3 cases. The tetany and CCF responded to calcium +/- magnesium infusions together with diuretics and in 2 cases, digoxin therapy. All 3 patients are well at present, and are controlled on 1-alpha-hydroxyvitamin D3 and calcium supplements. PMID- 3340969 TI - Pulsatile gluteal mass revealed as a false aneurysm of a persistent sciatic artery. A case report. AB - A 57-year-old black man presented with a pulsatile gluteal mass and claudication. Angiography revealed a persistent sciatic artery to be the main arterial supply to the limb; this vessel had a false aneurysm caused by atherosclerotic rupture of its gluteal portion. It was successfully treated by excision and an autologous vein graft. A brief survey of this rare condition -- the embryology, and the angiographic and clinical features -- is given. The importance of recognising the symptoms is emphasised. PMID- 3340970 TI - Closure of infected median sternotomy wound with pectoralis major muscle flaps. A report of 3 cases. AB - Three patients who developed mediastinal sepsis and sternal dehiscence after coronary artery bypass grafting were treated by closure of the wound using bilateral pectoralis major muscle flaps. Excellent cosmetic and functional results were obtained and morbidity was reduced. PMID- 3340971 TI - Late presentation of small-bowel injury--hypoproteinaemia, anaemia and obstruction. A report of 2 cases. AB - In contrast with traumatic intestinal perforation, the late sequelae of lesser small-bowel injury are not readily recognised. A protracted course of protein losing enteropathy as an intermediate result of traumatic segmental small intestinal ischaemia, and a fibrotic stricture with anaemia, intestinal obstruction and bezoar formation as a late result, are illustrated. PMID- 3340973 TI - Oral rehydration therapy for gastro-enteritis. PMID- 3340972 TI - Intravenous verapamil in the home management of supraventricular tachycardia. PMID- 3340974 TI - Computed tomographic findings in amebic brain abscess. PMID- 3340975 TI - Surgical infections. PMID- 3340976 TI - Multiple births: an upward trend in the United States. PMID- 3340977 TI - Women's longevity advantage declines. PMID- 3340978 TI - Trends in medical care costs. PMID- 3340979 TI - Variations in mortality from gastric cancer. PMID- 3340980 TI - The medical care cost dilemma. PMID- 3340981 TI - Radiochemotherapy. Workshop of the Section Radiooncology of the German Roentgenological Society, Hamburg, April 29, 1987. PMID- 3340982 TI - Multiple slice MR imaging as an aid in radiotherapy of carcinoma of the cervix uteri. A case report. AB - In recent years MRI has developed into an imaging modality with great potential for several medical disciplines including radiotherapy. A feature of particular relevance to radiotherapy is the possibility to depict arbitrarily orientated slices. Using multislice imaging techniques one can determine and describe tumour volume and extension in several directions. By doing so prior to and during radiotherapy it is possible to monitor response to treatment. In this case report of a patient treated for carcinoma of the uterine cervix the use of this MRI information is demonstrated. PMID- 3340983 TI - [3-D reconstruction of the breast implants from isocentric stereoscopic x-ray images for the application monitoring and irradiation planning of a remote controlled interstitial afterloading method]. AB - An individual irradiation planning and application monitoring by ISXP is presented for a remote-controlled interstitial afterloading technique using 192Ir wires which is applied in breast-preserving radiotherapy. The errors of reconstruction of the implants are discussed. The consideration of errors for ISXP can be extended to other stereoscopic methods. In this case the quality considerations made by other authors have to be enlarged. The maximum reconstruction error was investigated for a given digitalization precision, focus size, and object blur by patient's movements in dependence on the deviation angle. The optimum deviation angle is about 45 degrees, depending on the importance given to the individual parts and almost without being influenced by the relation between the isocenter-film and the focus-isocenter distances. In case of an optimized deviation angle, a displacement of an implant point of 1 mm leads to a maximum reconstruction error of 2 mm. The dosage is made according to the Paris system. If the circumcircle radius of the application triangle is modified by 1 mm, a dosage modification of 14% will be the consequence in case of very short wires and a small side length. A verification in a phantom showed a positioning error below 0.5 mm. The dosage error is 2% due to the mutual compensation of the direction-isotropic reconstruction errors of the needles the number of which is between seven and nine. PMID- 3340984 TI - Leaks occurring after gastric bariatric operations. AB - A leak from the stomach is the most serious complication that occurs after a gastric bariatric operation. The experience with 19 leaks that occurred after 791 gastric bariatric operations performed at North Carolina Memorial Hospital from 1975 to 1986 is described. The incidence of leaks was higher (8.3%) after a second than after a first gastric bariatric operation (2.0%). Ten leaks were life threatening and nine were not. There were no deaths. The diagnosis was made on the basis of Gastrografin swallow in seven patients, clinical findings in six, oral dye studies in three, barium study, a sinogram, and operation in one patient each. Thirteen of 16 patients were operated on within 4 hours of the diagnosis of a leak. One patient with a life-threatening leak and two with non-life threatening leaks were managed without operations. Three patients were discharged after uncomplicated courses and readmitted, and the diagnosis of a leak was established. To minimize morbidity and mortality related to a leak, it is imperative to (1) recognize that a leak can occur after any gastric bariatric operation, (2) perform a Gastrografin swallow when a leak is suspected, and (3) operate on the patient if the Gastrografin swallow is positive or if the clinical findings suggest a leak. PMID- 3340986 TI - Histopathologic studies of congenital dilatation of the bile duct as related to an anomalous junction of the pancreaticobiliary ductal system: clinical and experimental studies. AB - Clinical and experimental studies of congenital dilatation of the bile duct as related to an anomalous junction of the pancreaticobiliary ductal system were performed. Epithelial hyperplasia accompanied by round cell infiltration and increased thickness of the wall with fibrosis was observed histologically in the resected bile ducts of all 40 patients. Twenty-two of 26 patients (86.4%) who had bouts of abdominal pain showed that epithelial hyperplasia with round cell infiltration is dominant (glandular type), and 11 of 15 cases (73.7%) with persistent jaundice showed that thickness of the wall with fibrosis is dominant (fibrotic type). Amylase activities in bile of glandular-type cases obtained from the common bile duct intraoperatively were significantly greater than those of fibrotic-type cases (p less than 0.01). The common bile ducts of the canine model, in which whole pancreatic juice passed in the bile duct, dilated cylindrically 3.28 +/- 2.48 times in diameter after 24 to 41 days and histologically showed epithelial hyperplasia with round cell infiltration of the glandular type. These findings suggest that an anomalous junction of the pancreaticobiliary ductal system and the reflux of pancreatic juice into the bile duct affect not only clinical manifestations but also pathologic changes, especially of the glandular type, in patients with congenital dilatation of the bile duct. PMID- 3340985 TI - Long-term results and complications of preoperative radiation in the treatment of rectal cancer. AB - A retrospective study of 149 patients with rectal cancer diagnosed between 1972 and 1979 was undertaken to compare survival, disease-free survival, recurrence sites, and long-term complications of 40 patients who received 4000 to 4500 rads of preoperative adjuvant radiotherapy (radiation group) with those of 109 patients treated by resection alone (control group). After a mean follow-up of 84 months and 99 months, respectively, survival of the irradiated patients was significantly better than that of controls (68% versus 52%, p less than 0.05). Disease-free survival of those patients rendered free of disease by treatment was also superior for the irradiated group (84% versus 57%, p less than 0.005). Local recurrence without signs of distant metastases developed only one-third as often in irradiated patients (6% versus 18%). Distant metastases, alone or in combination with local recurrence, were also less common after radiation (12% versus 27%). Second primary tumors developed in 15% and 10% of the respective groups, a difference that was not statistically significant. When we consider the survival benefit of preoperative radiation therapy, long-term complications were relatively mild. Delayed healing of the perineum was noted in two irradiated patients. Persistent diarrhea was severe enough to warrant treatment in only one case, and one patient required a colostomy for intestinal obstruction from pelvic fibrosis. PMID- 3340987 TI - Fine-needle aspiration cytology in the diagnosis of primary breast cancer. AB - To evaluate the role of fine-needle aspiration (FNA) cytology in the diagnosis of primary breast cancer, we reviewed our experience over a recent 5-year period at Harbor-UCLA Medical Center. A total of 590 aspirates with subsequent follow-up were documented. One hundred thirty-three primary cancers were histologically proved. Of the 133 cancers, 91 (68%) were diagnosed as malignant by aspiration cytologic examination; another 22 (17%) were reported as suspicious. Of the cancers, 8 (6%) had a benign cytologic diagnosis and 12 (9%) had unsatisfactory smears. No cytologic tests positive for malignancy were found to be benign on histologic examination. With an absolute sensitivity of 75% and a specificity of 100%, we conclude that FNA cytologic examination is highly accurate in the diagnosis of breast cancer. With no false-positive studies, the finding of a clearly malignant cytologic condition obviates the need for biopsy before mastectomy. PMID- 3340988 TI - Transcutaneous oxygen measurements in lower extremity ischemia: effects of position, oxygen inhalation, and arterial reconstruction. AB - Transcutaneous oxygen tension (TcPO2) measurement has been successfully applied to the diagnosis and monitoring of patients with peripheral arterial insufficiency. This study was performed to assess the effects of changes in limb position, oxygen inhalation, and arterial reconstruction on TcPO2 values in patients with peripheral vascular disease. In addition, a TcPO2 index (foot TcPO2/chest TcPO2) was compared with the Doppler-derived ankle-to-brachial index (ABI) to determine which was the more effective monitor of the response to revascularization. Foot TcPO2 values of 22 patients with claudication or rest pain were measured before and after vascular reconstruction. TcPO2 increased after revascularization in both groups regardless of limb position or oxygen (O2) administration. The dependent position and O2 inhalation had an additive effect on TcPO2. Preoperative TcPO2 values in patients with rest pain showed the greatest response to the dependent position, increasing from 14 mm Hg to 33 mm Hg at room air and from 21 mm Hg to 53 mm Hg with O2 inhalation. TcPO2 in both patient groups was remarkably enhanced by O2 administration after revascularization. Postoperative supine TcPO2 values measured at room air increased from 50 mm Hg to 124 mm Hg (148%) in patients with claudication and from 40 mm Hg to 109 mm Hg (173%) in patients with rest pain after O2 inhalation. Comparison of the TcPO2 index with the ABI showed that absolute and normalized TcPO2 values are equally effective in monitoring peripheral arterial insufficiency. This study suggests that placing the limb in the dependent position and administering O2 may augment TcPO2 to levels where symptoms may resolve. The response of TcPO2 to O2 inhalation may be an indicator that reflects the response to revascularization. PMID- 3340989 TI - Seeding of ePTFE carotid interposition grafts in sheep and dogs: species dependent results. AB - Autologous endothelial seeding of thin-walled ePTFE vascular prostheses (I.D.4 mm), interposed in the carotid artery, was performed in 10 dogs and 14 sheeps. Aspirin (250 mg/day) and dipyridamole (75 mg/twice daily) were given throughout the study as antiplatelet therapy. Animals were killed 2 and 5 weeks after surgery. Patency rates for seeded grafts in dogs were 75% (6:8) and 83% (10:12) at 2 and 5 weeks, respectively. In control grafts the patency rates were identical. Patency rates for seeded grafts in sheep were 0% (0:5) and 11% (1:9) at 2 and 5 weeks, respectively. Control grafts in sheep had a patency rate of 40% (2:5) and 0% (0:9) at corresponding times. Scanning electron microscopy showed an almost complete endothelialization of seeded grafts in dogs after 5 weeks. Platelet deposition was studied in the dogs by means of chromium-51-labeled autologous platelets. Significantly fewer platelets accumulated on seeded grafts, and the ratio of 6-keto-PCF1 alpha to thromboxane B2 was significantly higher, compared with unseeded grafts, which indicated the presence of a functionally active endothelial lining in seeded grafts. Differences in the hemostatic system could account for the high clotting incidence in sheep, compared with that in dogs. Such species differences make extrapolations to the clinical situation from autologous endothelial seeding in experimental animals hazardous. PMID- 3340991 TI - Fluorescence assessment of skin perfusion after oral fluorescein. AB - This study evaluated oral ingestion as the route of fluorescein administration for fluorescence assessment of skin perfusion. In 10 anesthetized rats, dorsal pedicle flaps were raised to produce graded perfusion; then fluorescein (7.5 mg/kg) was administered via an oropharyngeal tube. Quantification of skin fluorescence, performed with the fiberoptic fluorometer 45 minutes after dye ingestion, delineated a significant difference between the perfusion of flap regions that remained viable and those that subsequently became dystrophic (p less than 0.05). The precision was equivalent to that previously reported after intravenous dye. In addition, the gradual delivery of dye after oral administration permitted monitoring of slope of uptake and time to peak. Each of these pharmacokinetic parameters delineated a significant difference between viable and nonviable sections. As measures of relative change in fluorescence, they are independent of skin color and thickness. This feature suggests that the oral route actually may improve the accuracy and reliability of the fluorescein test. PMID- 3340990 TI - Smooth muscle cell seeding in biodegradable grafts in rats: a new method to enhance the process of arterial wall regeneration. AB - In this study a smooth muscle cell seeding technique was developed and evaluated in biodegradable vascular grafts in rats. Cultured smooth muscle cells (3.5 to 5 X 10(6) in 0.1 ml whole blood) were seeded by means of a one-step preclotting technique in microporous, compliant, biodegradable vascular grafts (internal diameter 1.3 mm, length 1 cm; n = 16). Four seeded grafts as well as four nonseeded preclotted control grafts were histologically evaluated immediately after seeding and on preclotting; the other seeded grafts (n = 12) as well as nonseeded preclotted control grafts (n = 12) were implanted into the abdominal aorta of rats and were evaluated after 2 hours (n = 4), 2 days (n = 4), and 1 week (n = 4) with regard to the process of arterial wall regeneration. All grafts, except one seeded graft harvested at 1 week, were patent. All nonseeded control grafts showed no (at 2 hours and at 2 days) or limited (at 1 week) smooth muscle cell ingrowth. Of the 11 patent seeded grafts three also showed poor or limited neomedia development, probably because of improper preclotting. However, eight of the 11 patent seeded grafts showed fast and uniform noemedia development (clearly discernible at 2 days). Moreover, in two patent 1-week seeded grafts there were neomedia comparable in thickness and architecture (circularly arranged smooth muscle cells) to that of normal rat media, and a neointima had already lined 30% to 40% of the lumen. These results clearly demonstrate that smooth muscle cell seeding in biodegradable grafts is feasible and indicate that this seeding can enhance the process of arterial wall regeneration in these grafts. PMID- 3340992 TI - Experience with fully bioresorbable aortic grafts in the dog. AB - Reorganization of the arterial wall through natural processes on the resorption of a totally bioresorbable graft was investigated in dogs with Vicryl prostheses coated with two different blends of bioresorbable polyesters capable of slowing down considerably the disintegration of a Vicryl fabric in vivo. The prostheses (8 to 9 mm in internal diameter, 8 to 10 cm long) were implanted in the infrarenal aortic position for up to 24 weeks. All 18 animals implanted with coated prostheses survived, whereas one animal implanted with an uncoated Vicryl prosthesis died because of early rupture of the graft. Patent tubular conduits were present in 14 animals at the time of retrieval. On resorption of the synthetic polymers, the tissue layers that formed on both sides of the prosthetic material either fused or remained separated, depending on the polymer used as a retardant coating. We conclude that polymer composition influences the repair process and that a fully resorbable vascular graft can function effectively in a canine model, provided that tissue organization is sufficiently advanced by the time the prosthesis has lost its mechanical integrity. Further studies are needed to document the performance of the newly formed blood conduit over extended periods, in hypertensive subjects, and when presented with a bacterial challenge. PMID- 3340993 TI - Operative and long-term results of staged contralateral carotid endarterectomy: a personal series. AB - The operative risks as well as the proper interval for patients undergoing staged contralateral carotid endarterectomies remain uncertain. The long-term incidence of stroke after bilateral carotid endarterectomy is also poorly documented. In this report the results of staged contralateral carotid endarterectomies performed by one surgeon in a consecutive series of 89 patients are analyzed. No deaths occurred after a first or contralateral carotid endarterectomy. Four (4%) neurologic deficits (three minor and one major) occurred after a first operation, whereas only one (1%) major neurologic deficit occurred after a contralateral carotid endarterectomy. Postendarterectomy hypertension was noted in 33 (37%) patients after a first operation, and in 62 (70%) patients after a contralateral carotid endarterectomy (p less than 0.00001). No correlation existed among the intervals between carotid operations and the incidence or duration of hypertension after a contralateral carotid endarterectomy. From our results we conclude that the staged contralateral carotid endarterectomy can be safely performed with a stroke-mortality rate approaching 1%. Postendarterectomy hypertension, although more frequent after the contralateral operation as compared with the first operation, has no correlation with the interval between procedures. After a staged bilateral carotid endarterectomy, only one (1%) patient experienced transient ischemic attack symptoms, but five (6%) patients suffered late stroke (four fatal). PMID- 3340994 TI - Mycoplasma hominis surgical wound infection: a case report and discussion. AB - A patient with Mycoplasma hominis infection of a clean surgical wound that contained a prosthetic vascular graft had clinical findings similar to those observed in patients with acute bacterial infections. Etiologic diagnosis was delayed because M. hominis is not appreciated as a cause of surgical wound infections and because of its special growth characteristics. Confirmation of M. hominis infection requires awareness on the part of the clinician and assistance from an informed microbiologist. The organism can be recovered by means of media and techniques available in most microbiology laboratories. Although M. hominis has been reported to sporadically infect wounds, it is possible that many other wound infections with this organism are being missed. The clinical settings in which mycoplasmal infections might be expected are described. PMID- 3340995 TI - Pancreatoduodenectomy for periampullary cancer associated with celiac occlusion: a case report. AB - A 62-year-old man with atherosclerotic occlusion of the celiac axis underwent pancreatoduodenectomy because of cancer of the common bile duct. Preoperative angiography showed that the arterial blood supply to the celiac viscera was sustained through the gastroduodenal artery via the pancreaticoduodenal arcades from the superior mesenteric artery. Therefore reconstruction of the celiac circulation was attempted before division of the gastroduodenal artery. An autograft of the saphenous vein was placed between the infrarenal aorta and the common hepatic artery. The postoperative course was uneventful. Patency of the graft was demonstrated angiographically on the 50th postoperative day. PMID- 3340996 TI - A second opinion about thyroid hormone treatment. PMID- 3340997 TI - Hypercholesterolemia. PMID- 3340998 TI - Abdominal aortic aneurysm. PMID- 3340999 TI - Astronomical costs. PMID- 3341000 TI - [Atrophic rhinitis in cattle]. PMID- 3341001 TI - [Conjunctivitis....., or maybe not?]. PMID- 3341002 TI - [Observations with reference to the "Report by the Commission Animal Husbandry Animal Welfare"]. PMID- 3341003 TI - [The veterinarian and the free profession. Entrepreneurship as a requisite for a successful practice]. PMID- 3341004 TI - [The Veterinary Service Board. On the way to definitive identification and registration regulations for pigs and cattle]. PMID- 3341005 TI - [Influenza in piglets, back again?]. AB - A diagnosis of Mycoplasma hyopneumoniae infection in coughing piglets was verified using an ELISA technique by the Animal Health Service of the province of Limburg, the Netherlands. PMID- 3341006 TI - [Effect of international legislation on veterinary medicine in The Netherlands]. AB - The development of legislation in the veterinary field in the Netherlands under the influence of agreements with separate countries or that resulting from EEC directives is reviewed. The effects of international legislation on veterinary practice are elucidated with disease control in animals, equalization of certificates, animal welfare and the problem of residues. Effects on the authorities occur by way of EEC directives in the field of commercial traffic in fresh meat, fresh poultry meat and manufactured meats, bilateral agreements with third countries, international transport of animals and veterinary education. Attention is paid to the advisory role of the Federation of Veterinarians of the EEC (FVE) in EEC legislation in the veterinary field. In discussing future developments in legislation in the veterinary sphere, the Veterinary Medicinal Products Act, the Veterinary Surgeons' Act, the Animal Health and Welfare Act and the Integrated Surveillance System of the Animal and Meat Production Chain are referred to. PMID- 3341007 TI - [Bovine spongiform encephalopathy (BSE) in England, (The Netherlands?)]. PMID- 3341008 TI - [Epidemiology of Eimeria in broiler chicks as influenced by anticoccidial agents]. AB - 1,729 Flocks from seventy-three broiler farms, belonging to three integrated groups, were studied for the presence of coccidiosis during a five-year period. An overall average of 50.3 per cent of the flocks was found to be infected. There were marked difference between the integrated groups. Differences were also observed in the severity of infections, expressed in a relative coccidiosis score. A relatively high incidence of coccidiosis was particularly observed in autumn and winter flocks. Other conditions such as respiratory tract infections and leg defects were found to present a different seasonal pattern. Variations in the incidence of Eimeria species were observed during treatment with anticoccidial drugs. Repeated administration of the same agents resulted in changes in the spectrum; among other things, the number of mixed infections increased. Particularly so-called shuttle programmes using nicarbazin were found to be effective in suppressing coccidiosis. PMID- 3341010 TI - [The predictive value of urinalysis in the New Dutch Kidney Test]. AB - A urine test is described, by which a reliable indication of the time of slaughter is obtained in normal as well as in diseased animals, in which the New Netherlands Kidney Test (NNKT) will be negative. The test plate and testing procedure of the NNKT are used in this urine test. PMID- 3341009 TI - [Coccidiosis in broiler chicks: the prevalence of oocysts in feces in relation to necropsy findings in (sub)clinical coccidiosis and the effect of nicarbazin on these findings]. AB - Faecal samples were also collected from broiler farms presenting birds for autopsy. 126 Samples were examined, using two methods. Oocysts were detectable 3.5 days previously on an average before the presence of coccidiosis was determined at autopsy. Of the faecal samples 65.9 per cent were positive, and 46.0 per cent of the findings at autopsy were positive for coccidiosis. Examination of the faeces showed that more cases of mixed infection were present than could be concluded from autopsy. The largest number of oocysts was observed in E. acervulina infection, though large numbers of oocysts were also detected in cases of mixed infection. Treatment with nicarbazin during te first three weeks of life was found to delay the appearance of coccidiosis. The frequent use of withdrawal periods in the administration of anticoccidial drugs in view of 'thinning' showed high excretion rates. PMID- 3341011 TI - [A system of pharmacy organization]. PMID- 3341012 TI - [First isolation of Stuart-Schwan cocci in The Netherlands]. PMID- 3341013 TI - [Problems of estrus induction in sows]. PMID- 3341014 TI - Federation of Veterinarians of the EEC: burden or benefit? PMID- 3341015 TI - [The NOVAD--a new development (Netherland Organization for Automatization of Veterinary Practices)]. PMID- 3341016 TI - 17th annual meeting of the German Society for Thoracic and Cardiovascular Surgery. February 18th, 1988 to February 20th, 1988, Bad Nauheim. Abstracts. PMID- 3341017 TI - Human MHC class III (Bf, C2, C4) genes and GLO: their association with other HLA antigens and extended haplotypes in the Spanish population. AB - C4 allotype frequencies and their combination with factor B and C2 alleles (complotypes) were studied in a sample of the Spanish population in relation to MHC class I, class II and GLO alleles. The shorter genetic distances found for C4 between Spaniards and North Africans and the high frequency of extended HLA haplotypes (GLO 2) HLA-DR3 F1C30 HLA-B18 HLA-Cw5 (HLA-A30) and HLA-DR7 S1C21 HLA Bw50 HLA-Cw6 are consistent with a paleo-North African ethnic origin (about 20,000 years B.C.) of a part of present Spaniards (Iberians), and with the effect of racial admixture during late Moslem invasions (from the 8th to the 15th century). The complotype null alleles C4A QO and C4B QO may be under natural selection pressure when found in cis position, since they are never in the same haplotype in families. The underestimation of these C4 null alleles' frequencies in unrelated individuals as compared to genotyped families is shown to be a very likely event and a serious hindrance for C4-disease association studies. We have not found any C4 duplications in the Spanish population; this may be due to sample size limitations or to the degree of admixture of our population. Strikingly, no positive linkage disequilibrium between C4A and C4B alleles is detected in unrelated individuals nor in families, although strong associations are maintained among Bf, C2, C4, HLA-A, HLA-B, HLA-C and HLA-DR markers. Assuming that all MHC polymorphisms have reached equilibrium, several explanations are proposed, including the possibility of no, different or additional natural selection mechanisms operating on some MHC class III genes (Bf, C2, C4 alleles combinations for most appropriate C3 convertases), as compared to those affecting class I and class II gene clusters (most advantageous immune response genes sets). PMID- 3341018 TI - Mechanisms of regulation of rat hepatic metallothionein-I and metallothionein-II levels following administration of zinc. AB - The purpose of this study was to determine the role of transcription, translation, and protein degradation on the accumulation of metallothionein-I (MT I) and metallothionein-II (MT-II) in rat liver following induction of these proteins by Zn. The time course of MT induction indicated that concentrations of MT-I and MT-II, quantitated by high-performance liquid chromatography, were similar at 6 hr after administration of 1000 mumol Zn/kg (sc), but thereafter the concentration of MT-II was always higher than that of MT-I. By 24 hr after Zn administration, the concentration of MT-II in liver was more than two times that of MT-I. This difference increased with time such that by 96 hr the concentration of MT-II was more than five times that of MT-I. MT-I and MT-II mRNA levels, measured by Northern blot hybridization with mouse cRNA probes, increased coordinately following administration of Zn. MT mRNAs increased to maximum levels 6-9 hr after Zn administration, at which times MT-II mRNA was about two times more abundant than MT-I mRNA. MT mRNA levels remained elevated above control for as long as 36 hr after Zn administration. The relative rates of synthesis for MT I and MT-II were determined by quantitating incorporation of [35S]cysteine into MTs during a 2-hr period. For both proteins, the maximum relative rates of synthesis were observed 6-9 hr after administration of Zn, in parallel with the increase in mRNA levels. When MT synthesis was at maximal levels, there was approximately two times more [35S]cysteine incorporated into MT-II than MT-I, but at no other times were differences observed. In contrast to MT mRNA levels, MT synthesis returned to control levels by 24 hr after administration of Zn. Half lives of the isometallothioneins, determined by pulse-labeling experiments, were calculated to be 12.2 +/- 0.8 and 21.9 +/- 3.0 hr for MT-I and MT-II, respectively. Thus, Zn treatment increases transcription of both MT-I and MT-II genes and the synthesis of MT-I and MT-II. However, Zn-induced MT-II is more stable than MT-I. These results suggest that differences in the rate of synthesis and degradation of MT-I and MT-II lead to a greater and more prolonged induction of MT-II following administration of Zn. PMID- 3341020 TI - The role of trichloracetic acid and peroxisome proliferation in the differences in carcinogenicity of perchloroethylene in the mouse and rat. AB - Fischer 344 rats and B6C3F1 mice of both sexes were exposed to 400 ppm perchloroethylene (PER) by inhalation, 6 hr/day for 14, 21, or 28 days or to 200 ppm for 28 days. Increased numbers of peroxisomes were seen under the electron microscope and increased peroxisomal cyanide-insensitive palmitoyl CoA oxidation was measured (3.6-fold increase in males and 2.1-fold increase in females) in the livers of mice exposed to PER. Hepatic catalase was not increased. Peroxisome proliferation was not observed in rat liver or in the kidneys of either species. Trichloracetic acid (TCA), a known carcinogen and hepatic peroxisome proliferating agent, was found to be a major metabolite of PER. Blood levels of this metabolite measured in mice and rats during and for 48 hr after a single 6 hr exposure to 400 ppm PER showed that peak blood levels in mice were 13 times higher than those seen in rats. Comparison of areas under the curves over the time course of the experiment showed that mice were exposed to 6.7 times more TCA than rats. The difference in metabolism of PER to TCA in mice and rats leads to the species difference in hepatic peroxisome proliferation which is believed to be the basis of the species difference in hepatocarcinogenicity. Peroxisome proliferation does not appear to play a role in the apparent carcinogenicity of PER in the rat kidney. PMID- 3341019 TI - Ontogeny and induction of hepatic isometallothioneins in immature rats. AB - It is well established that hepatic concentrations of metallothioneins (MTs) are very high in developing rats. In this study, the ontogeny of hepatic isometallothioneins (MT-I and MT-II) was determined. MTs were separated and quantitated with a high-performance liquid chromatography (HPLC) method. MT-I and MT-II, first detected in fetal liver on gestation Day 18, increased coordinately during late gestation and reached maximum hepatic concentrations of approximately 400 and 500 micrograms/g, respectively, which were maintained from postpartum Days 1 through 7. Thereafter, MT concentrations decreased, reaching concentrations similar to adult levels (approximately 10 micrograms/g liver) between 28 and 35 days of age. MT-II was significantly higher than MT-I in 14- and 21-day-old rats. In 35-day-old rats, MT-I was below the detection limit. MT-I and MT-II mRNA levels were quantitated by Northern blot hybridization with mouse cRNA probes. In contrast to protein concentrations, MT mRNA reached maximal levels during late gestation which were maintained throughout the first 3 weeks postpartum. Additional experiments indicated that Cd (1-30 mumol/kg), Zn (100 3000 mumol/kg), and dexamethasone (0.3-10 mumol/kg) increased hepatic concentrations of MT-I and MT-II and their respective mRNAs in 14-day-old rats, despite the preexisting high levels of protein and mRNA at this time. These results indicate that hepatic concentrations of MT-I and MT-II isoproteins and mRNA, which increase coordinately during fetal development, decline differently during neonatal development. In 14-day-old neonates, MT-I and MT-II genes are responsive to Cd, Zn, and dexamethasone when constitutive levels of both MT mRNA and isoproteins are high. PMID- 3341021 TI - Alteration of multiple cell membrane functions in L-6 myoblasts by T-2 toxin: an important mechanism of action. AB - Recent studies suggest that T-2 toxin interacts with cell membranes and alters membrane function. This study was done to assess the effect of T-2 toxin on a broad range of cell membrane functions in L-6 myoblasts. The following parameters were assessed after exposure to T-2 toxin for 10 min: (1) the uptake of calcium, rubidium, and glucose; (2) the uptake of leucine and tyrosine and incorporation into protein; (3) the uptake of thymidine and incorporation into DNA; and (4) residual cellular lactate dehydrogenase (LDH) as a measure of cell membrane integrity. The effects of T-2 toxin on these parameters were: (1) The minimal effective concentration (MEC) of T-2 toxin that caused a reduction in the uptake of calcium and glucose was 4 pg/ml. The uptake of rubidium was increased at 0.4 pg/ml and then reduced at 4 pg/ml and higher concentrations. (2) The MEC for reduction of the uptake of leucine and tyrosine and their incorporation into protein was 4 pg/ml. (3) Thymidine uptake and incorporation into DNA showed a biphasic response with an increase at 0.4 pg/ml and a reduction at 4 pg for uptake and 40 pg/ml for incorporation. (4) Intracellular LDH was reduced at 4 ng/ml. (5) Calcium efflux was reduced after 1-, 5-, and 15-min exposures to T-2 toxin in a concentration of 40 ng/ml. All of the changes noted, including protein synthesis inhibition, were present to a significant degree within 10 min of exposure to T-2 toxin. This time interval is too short to attribute all of these effects directly to protein synthesis inhibition since most short-lived proteins have half-lives measured in hours. In conclusion, T-2 toxin appears to have multiple effects on cell membrane function at very low concentrations (0.4 pg/ml to 4 ng/ml), which are independent of protein synthesis inhibition. These likely include effects either direct or indirect on amino acid, nucleotide, and glucose transporters, as well as calcium and potassium (rubidium) channel activities. PMID- 3341022 TI - Inducing effect of albendazole on rat liver drug-metabolizing enzymes and metabolite pharmacokinetics. AB - Albendazole (ABZ), methyl (5-(propylthio)-1H-benzimidazol-2-yl)carbamate, is a broad spectrum anthelmintic drug. S-oxidation to the sulfoxide (SO-ABZ) and the sulfone (SO2-ABZ) are the first steps of its bioconversion. SO-ABZ is pharmacologically active and embryotoxic in rats. In the present study, rat liver microsomal drug-metabolizing enzymes were assayed after 10 days oral administration with 40 mumol ABZ/kg per day. The activities of 4-nitroanisole O demethylase, benzo[a]pyrene hydroxylase, 7-ethoxycoumarin O-deethylase, and 7 ethoxyresorufin O-deethylase increased 6-, 7-, 8-, and 30-fold, respectively. By immunoblotting an increase in cytochrome P-448 was observed. UDP glucuronosyltransferase (GT) type 1 activities (1-naphthol, 7-hydroxycoumarin, 4 nitrophenol, and 4-methylumbelliferone) were significantly higher than in control microsomes (3- to 4-fold), while GT type 2 activities and bilirubin-GT remained unchanged. Microsomal epoxide hydrolase (benzo[a]pyrene oxide) increased 2-fold. Microsomal gamma-glutamyltransferase activity was unchanged. The in vivo SO-ABZ plasma level was decreased when the SO2-ABZ plasma level was increased. In vitro sulfoxidation and sulfonation were, however, unchanged. Although a range of imidazole derivatives, including benzimidazole itself, were commonly reported as inhibitors of monooxygenase activities, ABZ behaved as an inducer of cytochrome P 448, GT1, and epoxide hydrolase. PMID- 3341023 TI - Nongenotoxicity of minoxidil in murine hair follicles as determined by the nuclear aberration assay. AB - A 1-cm2 area on the back of CD1 mice was prepared for topical application of minoxidil, N-methyl-N-nitrosourea (MNU), or cyclophosphamide (CY) by clipping or plucking hair from a patch of skin. Plucking stimulates hair follicle cell division while clipping does not. Minoxidil was topically administered for 8 consecutive days. CY or MNU was administered topically once on the eighth day postplucking. The incidence of nuclear aberrations and mitotic figures were measured in hair follicles while frequency of micronuclei and the ratio of RBC/PCE were measured in the bone marrow. Results with minoxidil showed no increase in either nuclear aberrations in the hair follicle or micronuclei in the bone marrow. These results suggest that topically applied minoxidil is not genotoxic. In contrast, a dose-dependent effect of MNU on the incidence of nuclear aberrations in the hair follicle was seen. CY induced a dose-dependent increase in the incidence of micronuclei in the bone marrow and in nuclear aberrations in the hair follicle after topical application. Minoxidil applied to clipped mice significantly increased the incidence of mitotic figures above that seen in both the clipped and plucked controls. This suggests that minoxidil is a mitogenic agent in the hair follicle. These findings are consistent with the success of topically applied minoxidil in the treatment of alopecia areata. PMID- 3341024 TI - Rat testis during 2,5-hexanedione intoxication and recovery. I. Dose response and the reversibility of germ cell loss. AB - The histopathology of the testicular injury induced by 2,5-hexanedione (2,5-HD) exposure was examined in the rat. Charles River CD rats (200 g) were intoxicated by consuming 1% 2,5-HD in the drinking water or by intraperitoneal injection of the toxicant. Both neurotoxic and subneurotoxic exposures were studied, the total dose ranging from 40 to 211 mmol/kg. The following results were obtained: (1) there was a time delay between administration of the toxicant and development of the testicular injury, (2) Sertoli cell vacuolation in stages associated with the meiotic metaphase was the first histological sign of cellular injury at all doses, (3) subneurotoxic doses produced selective defects in germ cells in stages I-VIII of the spermatogenic cycle, (4) both subneurotoxic and neurotoxic doses produced germ cell necrosis and generalized sloughing of germ cells, and (5) intensive intoxication followed by a 17-week recovery period resulted in an absence of all postspermatogonial germ cells from the seminiferous epithelium of three of five treated rats. These data demonstrate that 2,5-hexanedione-induced testicular atrophy occurs at exposure levels below those producing clinical neurotoxicity and that, within the time frame of this study, the testicular injury is at least partially irreversible. PMID- 3341025 TI - Rat testis during 2,5-hexanedione intoxication and recovery. II. Dynamics of pyrrole reactivity, tubulin content, and microtubule assembly. AB - Charles River CD rats (200 g) were intoxicated with 1% 2,5-hexanedione (2,5-HD) in the drinking water for 5 weeks followed by a 17-week recovery period. Pyrrole reactivity of testis proteins increased early during intoxication and then returned toward normal during recovery. Testis tubulin content first increased as germ cells were lost and then fell over time while atrophy was maintained. Purified testis tubulin demonstrated a decreased nucleation time for microtubule assembly at 2 weeks, maintained this alteration throughout intoxication, and then returned to normal assembly kinetics during recovery. The assembly abnormality was accompanied by the presence of a unique crosslinked tubulin species. These findings support the hypothesis that alterations in Sertoli cell microtubules result in germ cell loss following 2,5-HD exposure. PMID- 3341027 TI - A comparison of the effects of the three isomers of dinitrobenzene on the testis in the rat. AB - Sexually mature Alpk/AP (Wistar derived) rats were killed 5 days after a single oral dose of 50 mg/kg of the 1,2-, 1,3-, or 1,4-isomers of dinitrobenzene. Testis weight reductions accompanied by testicular lesions were observed in the animals dosed with 1,3-dinitrobenzene (1,3-DNB) while the 1,2- and 1,4-isomers were without effect on the testis. However, 1,4-dinitrobenzene, but not 1,2 dinitrobenzene, was of a potency similar to that of 1,3-DNB in producing cyanosis and splenic enlargement in these animals, indicating that different mechanisms are probably responsible for these two toxic effects. In a subsequent study the pathogenesis of the testicular damage resulting from a single oral dose of 5, 10, 15, or 25 mg 1,3-DNB/kg was studied in sexually mature rats. Animals were killed 6, 12, 24, 48, and 96 hr after dosing and a detailed histopathological examination of the testes and selected tissues was made. At 12 hr after a single oral dose of 25 mg/kg, 1,3-DNB produced testicular lesions limited to Stages VIII to XI of the spermatogenic cycle. By 24 hr widespread Sertoli cell damage was evident and in some tubules was associated with degeneration of primary spermatocytes. Ultrastructural examination at this time confirmed that there were effects on Sertoli cells in the absence of germ cell damage. Similar effects were seen 48 hr after a single oral dose of 15 mg 1,3-DNB/kg. Doses of 5 or 10 mg 1,3 DNB/kg were without effect on the testis. The Sertoli cell is implicated as the prime target for the toxic action of 1,3-DNB with germ cell damage a secondary event. PMID- 3341026 TI - High doses of soman protect against organophosphorus-induced delayed polyneuropathy but tabun does not. AB - Organophosphorus-induced delayed polyneuropathy (OPIDP) is thought to result from organophosphorylation of neuropathy target esterase (NTE; formerly known as neurotoxic esterase), followed by an "aging" of the phosphorylated NTE. Protection against OPIDP should thus be achieved by production of an inhibited but "nonaging" NTE. Inhibited NTE produced in vitro by interaction with any of the four resolved isomers of soman aged negligibly (M. K. Johnson, D. J. Read, and H. P. Benschop, 1985a, Biochem. Pharmacol., 34, 1945-1951). Therefore both unresolved soman and the most inhibitory isomer (C(-)P(+)) were tested in adult hens for effects on NTE and for ability to produce OPIDP. With improved prophylaxis and therapy of acute intoxication, birds survived greater than 100 X LD50 of unresolved soman and did not develop OPIDP. One day after dosing, about half of brain and spinal cord NTE was in an unmodified (unaged) inhibited form; at this time eight survivors were challenged with a neuropathic dose of diisopropyl phosphorofluoridate (DFP). No neuropathy developed in four out of eight birds and mild to moderate signs were seen in the other four. Nine challenge control birds receiving DFP after solvent all developed severe neuropathy. Partial protection was seen in three out of three birds dosed prior to DFP challenge with sufficient C(-)P(+) isomer of soman (1.2 mg/kg sc) to convert about half of the spinal cord NTE to unaged inhibited form. Protection was not related to cholinergic shock. Two birds which survived out of eight pretreated with tabun (12 mg/kg sc) had about as much NTE inhibited as after soman administration but it was all in the modified (aged) inhibited form; these birds were not protected against DFP-induced neuropathy. A limited histopathologic examination showed that typical neurodegenerative lesions were seen only in birds with clear clinical neuropathy. PMID- 3341029 TI - Comparative neurotoxicity and pyrrole-forming potential of 2,5-hexanedione and perdeuterio-2,5-hexanedione in the rat. AB - 2,5-Hexanedione (2,5-HD), the neurotoxic metabolite of n-hexane, reacts with protein amines to form alkylpyrrole adducts. Pyrrolylation of neurofilament protein may be the initiating molecular event in 2,5-HD neuropathy. The present study compares the neurotoxic and pyrrole-forming potentials of 2,5-HD with those of perdeuterio-2,5-HD ([D10]-2,5-HD) in the rat. Due to a requirement for C-H bond breaking in the reaction mechanism, the latter derivative was expected to exhibit a primary isotope effect, thus forming the pyrrole at a slower rate. In vitro studies confirmed that [D10]-2,5-HD pyrrolylated protein at only one-third of the initial rate seen with native 2,5-HD. Prolonged incubation resulted in similar pyrrole concentrations with both derivatives. Adult, male Wistar rats were administered daily (5 days/week) ip doses of either 3.5 mmol 2,5-HD or [D10] 2,5-HD/kg/day for 17 days or 2.5 mmol/kg/day for 38 days. At termination, animals administered 2,5-HD and [D10]-2,5-HD exhibited 27 and 8% body weight loss, respectively. Moderate to severe hindlimb paralysis was present in the 2,5-HD groups while only mild effects were seen in [D10]-2,5-HD-dosed rats. Neuropathological changes were prominent in spinal cord sections from 2,5-HD treated animals, while no effects were present in rats given the deuterated derivative. Pyrrole adduct concentrations in serum and axonal cytoskeletal proteins from 2,5-HD-treated animals were two- to threefold higher than in rats given equimolar doses of [D10]-2,5-HD. Levels of covalent crosslinking of axonal cytoskeletal proteins (assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) appeared to correlate with pyrrole concentrations. Tissue concentrations of each diketone isomer were not significantly different, indicating similar uptake of native and deuterated 2,5-HD. Mass spectrometry revealed rapid back exchange of the terminal (methyl) but not of the internal (methylene) deuteriums of [D10]-2,5-HD in vivo. These findings support an absolute requirement for pyrrole formation in gamma-diketone neurotoxicity. PMID- 3341028 TI - Activity of thyroid hormone-inducible enzymes following treatment with 2,3,7,8 tetrachlorodibenzo-p-dioxin. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) caused a depletion of serum thyroxine, but paradoxically did not change L-3,5,3'-triiodothyronine (T3) levels in serum of rats. The activities of the thyroid-regulated enzymes alpha-glycerol phosphate dehydrogenase (GPD) and malic enzyme (ME) were determined in livers of normal and thyroidectomized (THX) rats treated with 0.1 to 100 nmol TCDD/kg body weight. Mitochondrial GPD activity did not change significantly as a function of TCDD dose in either normal or THX rats. ME activity was induced by TCDD in a dose dependent fashion, but only in non-THX animals. The absence of ME induction in THX rats treated with TCDD indicates that TCDD is not intrinsically thyromimetic. The dependence of ME induction on thyroid hormones is much like the thyroid hormone-dependent, multihormonal induction of ME by insulin and glucocorticoids. However, TCDD had no additive or synergistic effects on induction of ME activity in THX rats fed T3. A 30% decrease in steady-state plasma T3 levels of T3-fed animals treated with TCDD relative to T3-fed controls suggested that T3 catabolism was more rapid in TCDD-treated rats than controls. Thus a thyroid hormone-dependent, multihormonal interaction is suggested as the basis for induction of ME by TCDD, but a strictly T3-dependent process has not been ruled out. PMID- 3341030 TI - Kidney synthesizes less metallothionein than liver in response to cadmium chloride and cadmium-metallothionein. AB - Acute exposure to Cd produces liver injury, whereas chronic exposure results in kidney injury. Tolerance to the hepatotoxicity is observed during chronic exposure to Cd due to the induction of metallothionein (MT). The nephrotoxicity produced by chronic Cd exposure purportedly results from renal uptake of Cd metallothionein (CdMT) synthesized in liver. The change in target organ from liver to kidney might be due to a lower amount of MT synthesized in the kidney in response to CdMT. Therefore, the purpose of the present study was to quantitate hepatic and renal MT induced by CdCl2 and CdMT. MT levels in mice were quantitated using the Cd-heme assay 24 hr after administration of CdCl2 (0.5-3.0 mg Cd/kg) and CdMT (0.1-0.5 mg Cd/kg). In both liver and kidney, MT reached higher levels following administration of CdCl2 (220 and 60 micrograms/g, respectively) than of CdMT (25 and 35 micrograms/g, respectively), probably because higher dosages of CdCl2 than CdMT are tolerated. CdMT produced 19 and 3 micrograms MT/micrograms Cd in liver and kidney, respectively, while CdCl2 produced 11 and 6 micrograms MT/micrograms Cd, respectively. In conclusion, induction of MT occurs in both the liver and kidney after administration of CdCl2 and CdMT. However, the kidney is less responsive than the liver to the induction of MT by both forms of Cd, which may contribute to making the kidney the target organ of toxicity during chronic Cd exposure. PMID- 3341031 TI - Role of the 4-hydroxy intermediate in the in vitro embryotoxicity of cyclophosphamide and dechlorocyclophosphamide. AB - Cyclophosphamide must be metabolically activated to produce malformations in cultured rat embryos. A 4-hydroxylated intermediate, 4-hydroxycyclophosphamide is initially formed during this activation. While 4-hydroxycyclophosphamide (and/or its open-ring tautomer, aldophosphamide) is believed to act as a transport form in mediating the antineoplastic activity of cyclophosphamide, its role in the teratogenicity of this drug is not known. In this study the effects of two "preactivated" cyclophosphamide analogs on cultured Day 10 rat embryos were determined. The first analog, 4-hydroperoxycyclophosphamide, is converted to 4 hydroxycyclophosphamide in aqueous solutions, releasing both acrolein and phosphoramide mustard, while the second, 4-hydroperoxydechlorocyclophosphamide, releases, in a similar manner, acrolein and the inactive metabolite, phosphoric acid diamide. Both cyclophosphamide analogs were teratogenic, embryolethal, and growth retarding in vitro, but the effective concentrations and the types of malformations produced were different. 4-Hydroperoxycyclophosphamide produced embryo deaths and malformations and decreases in embryonic growth and protein content at concentrations in the range of 5 to 25 microM. In contrast, 4 hydroperoxydechlorocyclophosphamide did not produce embryo deaths at concentrations below 100 microM and produced embryo malformations and growth retardation only at 125 microM. The concentration-response curve and the spectrum of malformations produced by 4-hydroperoxycyclophosphamide resembled those previously reported for phosphoramide mustard, while the concentration-response curve and types of malformations produced by 4 hydroperoxydechlorocyclophosphamide more closely resembled those observed with acrolein. Thus, the 4-hydroxy intermediates are similar as teratogens to the most potent of the metabolites which they produce; the 4-hydroxy compounds may serve as a transport form of cyclophosphamide but do not appear themselves to have a major role in teratogenicity. PMID- 3341032 TI - Effect of intratracheal gallium arsenide administration on delta-aminolevulinic acid dehydratase in rats: relationship to urinary excretion of aminolevulinic acid. AB - Exposure to gallium arsenide (GaAs) is a potential hazard in the semiconductor industry and there is a need for specific biological indicators of exposure/toxicity for this compound. These studies examined effects of GaAs exposure on the heme biosynthetic pathway enzyme delta-aminolevulinic acid dehydratase (ALAD). Male CD rats received GaAs suspensions at doses of 50, 100, or 200 mg/kg via a single intratracheal instillation. Six days after treatment a dose-dependent inhibition of blood ALAD was observed with activity decreasing to 5% of controls at the highest dose, with a concomitant marked increase in the urinary excretion of aminolevulinic acid (ALA). Inhibition of blood ALAD following administration of GaAs was maximal (30% of control) 3 to 6 days postexposure and returned to approximately control values on day 18. Urinary excretion of ALA was maximal 3 to 6 days postexposure and recovered toward control values at 18 days. Inhibition of kidney and liver ALAD following GaAs exposure was also evident. Intratracheal instillation of silica did not alter the activity of ALAD in blood, liver, or kidney. Marked increases in lung wet weight/body weight ratios were evident in lungs of silica- and GaAs-treated rats. Histopathological changes in the lungs were characterized by multifocal granulomas following silica treatment and Type II pneumocyte hyperplasia following GaAs treatment; mild necrosis was evident in both groups. Rats treated with 100 mg/kg GaAs exhibited swelling of kidney proximal tubule mitochondria 6 days following exposure. Silica and GaAs exposure produced marked decreases in cumulative weight gain. The concentration of gallium required to achieve half maximal inhibition of ALAD in vitro was 200-fold less in blood and 40-fold less in kidney and liver than that required for arsenite and the inhibition was partially prevented by excess zinc. These data suggest that gallium is the primary inhibitor of ALAD following dissolution of GaAs in vivo and that competition for or displacement of zinc from the enzyme active site may be involved in the mechanism of inhibition. The data also demonstrated the utility of including a particulate control group when assessing the chemical-induced toxicity of compounds administered intratracheally as particulate suspensions. Finally, measurement of heme precursors, e.g., ALA, in urine coupled with assay of red blood cell ALAD activity may be of value as an early biological indicator of GaAs exposure and/or toxicity. PMID- 3341033 TI - Effect of diethyl maleate on hepatic ornithine decarboxylase. AB - Diethyl maleate (DEM), a well-known glutathione (GSH) depletor, causes a dose dependent increase in hepatic ornithine decarboxylase (ODC) activity as well as heme oxygenase activity in rats. Considering the important role ODC has in polyamine biosynthesis in response to endogenous and exogenous stimuli, further extensive studies on the effect of DEM on ODC in relation to its GSH-depleting effect were carried out. Specifically, concomitant with the profound decrease in GSH content, the higher dose of DEM (1284 mg/kg) caused a marked increase in ODC activity (about 1000 times that of the control) at 12 hr after its administration. DEM at this dose also caused a marked increase in heme oxygenase activity, but the effects on cytochrome P-450 content and aminopyrine demethylase activity were less extensive. The increases in ODC and heme oxygenase activities evoked by DEM were almost completely blocked by pretreatment of rats with either actinomycin D or cycloheximide. Parallel to the increase in ODC activity, DEM caused a profound increase in putrescine content in the liver, while the agent reduced spermine content. The administrations of alpha-difluoromethylornithine and 1,3-diaminopropane resulted in the inhibition of DEM-mediated induction of ODC, but not heme oxygenase. In contrast, methylglyoxal bis(guanylhydrazone) inhibited the induction of both ODC and heme oxygenase evoked by DEM. The DEM induced ODC exhibited two phases of decay with the prolonged half-lives of 26 and 223 min. Additionally, the elution profile from DEAE-Sepharose CL-6B column chromatography of cytoplasmic fraction from DEM-treated rat liver exhibited two peaks of ODC activity. These findings add new insight into the biochemical effect of DEM on hepatic polyamine metabolism in addition to its GSH-depleting effect. PMID- 3341034 TI - Types of adrenocorticoids and their effect on organophosphorus-induced delayed neuropathy in chickens. AB - The present study examined the effects of a glucocorticoid and a mineralocorticoid on organophosphorus-induced delayed neuropathy (OPIDN) as previous investigations have indicated that an endogenous steroid with both properties could alter this syndrome in chickens. The glucocorticoid triamcinolone and the mineralocorticoid deoxycorticosterone were provided in the diet beginning 1 day before and continuing 10 days after triortho-tolyl phosphate (TOTP, 360 mg/kg po), phenyl saligenin phosphate (PSP, 2.5 mg/kg im), and diisopropyl phosphorofluoridate (DFP, 1 mg/kg sc). In a manner similar to that seen with corticosterone, a low concentration (0.1 ppm) of triamcinolone reduced and a high concentration (10 ppm) exacerbated clinical signs. Concentrations of deoxycorticosterone under 80 ppm also partially delayed or ameliorated ataxia induced by TOTP, PSP, and DFP, but a combination of 0.1 ppm triamcinolone and 80 ppm deoxycorticosterone was not more effective than triamcinolone alone. Peripheral nerve damage was noted in all chickens given organophosphorus compounds, whether or not they had been given corticoids. Both steroids induced hydroxylase activity, but effects on most other enzyme systems examined were unremarkable. High concentrations of triamcinolone (10 ppm) could, however, also reduce liver cytochrome P450 levels and liver cholinesterase activity. Exacerbation of OPIDN was most notable in chickens under highest stress, as indicated by elevated heterophil-to-lymphocyte ratios. The clinical, pathological, biochemical, and hematological indices of exposure to adrenocorticoids and agents inducing OPIDN in chickens were, therefore, similar for both a synthetic glucocorticoid and the endogenous steroid corticosterone. PMID- 3341035 TI - Histological localization of methylmercury in mouse brain and kidney by emulsion autoradiography of 203Hg. AB - Some investigators have abandoned the use of 203Hg emulsion autoradiography in favor of chemical methods of microscopic localization of mercury. However, recent studies indicate that the latter methods identify only inorganic mercury, or some product of inorganic mercury, making them of little or no value for studies of methylmercury toxicity. Doubts about the use of 203Hg for microscopic localization arose because of the high maximum energy of its emissions and the concern that its latent images might be confounded with silver grains produced by chemical reactions between tissue Hg and the silver supplied by photographic emulsions. Examination of the spectrum of emissions from 203Hg demonstrates that its maximum energy emissions are rare. The mean energy of 203Hg emissions is in the 50-ke V range and the modal emissions are close to 0 ke V, indicating sufficient low energy emissions for autoradiography. In preliminary experiments, methylmercury content of mouse brain was shown to be stable through the steps of tissue processing for plastic sections. A direct comparison of autoradiographic grain counts from tissue treated with "cold" or "hot" methylmercury demonstrated that no grains above background were produced in the absence of nuclear emissions -only "hot" samples affected emulsion. In the kidneys of mice killed 24 hr after dosing, grains were most numerous over cortical tubules and significantly less numerous over glomeruli. In the cerebellum, the molecular layer was significantly more heavily labeled than the granular layer. The number of grains was greatly increased in every region by increasing the specific activity of the methylmercury dosing solution while holding the dose of methylmercury constant. Like the differential effect of "hot" vs "cold" tissue, the differential effect of low vs high specific activity confirms that the grain counts reflect nuclear emissions from the sample tissues, rather than a chemical effect dependent only on mercury content. Grain counts provided a measure of methylmercury content that matched the content measured by atomic absorption (AA). For example, the ratio of kidney/brain content was 32 by AA and 31 by grain counts in one experiment. Thus, 203Hg emulsion autoradiography appears to be a useful approach to localization of methylmercury in tissue sections processed for light microscopy. PMID- 3341036 TI - Effect of preexposure to dietary benzo[a]pyrene (BP) on the first-pass metabolism of BP by the intestine of toadfish (Opsanus tau): in vivo studies using portal vein-catheterized fish. AB - The effect of preexposure of fish to dietary benzo[a]pyrene (BP) on the intestinal metabolism of BP was examined in toadfish (Opsanus tau). The portal veins of toadfish were cannulated following administration of radiolabeled BP to the intestinal lumen. Because these fish lack a lymphatic vessel system, the portal vein is the sole route by which BP and its metabolites enter the circulation. In fish preexposed to dietary BP (10 mg BP/kg food), the radioactivity entering the portal vein was almost entirely (ca. 90%) BP metabolites. In fish fed a laboratory control diet, a smaller percentage (ca. 60%) of the radioactivity entering the portal vein was in the form of BP metabolites. The enhanced efficiency of the intestines of preexposed fish in metabolizing BP appears to be a result of induction of intestinal aryl hydrocarbon hydroxylase (AHH) activity. Intestinal microsomal AHH activities in control and preexposed fish were 0.033 +/- 0.032 and 0.320 +/- 0.060 nmol.min 1.mg-1, respectively. Gel filtration of portal vein plasma indicated differences in the roles of plasma proteins in transporting BP and BP metabolites. Native BP was associated primarily with the high density lipoproteins, whereas organic soluble BP metabolites were associated primarily with serum albumin fractions. A large percentage of BP metabolites was recovered as water-soluble conjugates. These studies indicate that in fish, the intestine can be an important organ involved in dietary BP metabolism. PMID- 3341038 TI - Age-related morphometric differences in responses of rat lungs to ozone. AB - The influence of age on morphologic changes in lungs of rats exposed to ozone was studied in female Sprague-Dawley rats, aged 60 and 444 days. Rats of both age groups were exposed continuously for 72 hr to either 0.35 or 0.80 ppm ozone, or to filtered air. Tissues were evaluated using light microscopic morphometry and scanning electron microscopy. The lungs from ozone-exposed 60-day-old rats had larger volume fractions of centriacinar lesions than lungs from exposed 444-day old rats. Within each age group there was an observed dose response, with rats exposed to 0.80 ppm ozone having larger volume fractions of lesions than those exposed to 0.35 ppm. Only the 444-day-old rats lost body weight during the exposure period. They also had smaller fixed lung volumes than same-aged controls. All 60-day-old rats gained weight during the exposure period, although rats exposed to 0.80 ppm ozone gained less than filtered air controls. Lesions observed in both age groups of female rats were qualitatively similar to those previously described in young adult male rats. We conclude that there are age related differences in the morphometric responses of rats to ozone exposure. Younger rats had larger proportions of centriacinar lesions and macrophages while older rats had greater body weight and lung volume changes. PMID- 3341037 TI - Prenatal dinocap exposure alters swimming behavior in mice due to complete otolith agenesis in the inner ear. AB - Exposure to the fungicide dinocap during gestation produces behavioral abnormalities in the house mouse that are not apparent at birth but become obvious at weaning. Pregnant mice (CD-1) were exposed on Days 7 to 16 of gestation to dinocap at 0, 6, 12, or 25 mg/kg/day and the postnatal behavioral development of the offspring was assessed. Torticollis (head-tilting) appears in the treated offspring at 3 weeks of age (4.4% at 12 and 25.3% at 25 mg/kg/day) and, during a test of swimming ability, many of the mice (6.8% at 12 and 47.2% at 25 mg/kg/day) sink below the surface or are unstable and swim on their side in the water. These behavioral abnormalities are the result of agenesis of the otoliths in the inner ears. These were the only developmental defects noted in the 12 mg/kg/day dosage group. In this group 4.4% of the mice displayed torticollis, 9.2% did not swim normally, 19% were missing one or more whole otoliths (7.7% were missing all four otoliths), and partial agenesis of the crystalline material was seen in an additional 11.6% of the mice. The frequency of behavioral and inner ear defects increased in the higher dosage group, but the order of sensitivity of the effects did not change. PMID- 3341039 TI - Reactivation and aging of phosphorylated brain acetylcholinesterase from fish and rodents. AB - Species-related differences in sensitivity to acute intoxication by anticholinesterase compounds have been attributed, in large part, to differences in the kinetics of inhibition of acetylcholinesterase (AChE) in vitro. Since inhibition of AchE is also influenced by the stability of the phosphorylated enzyme complex, it was of interest to compare the rates at which the inhibited enzyme from different species subsequently either reactivates or ages. Brain AChE from rats, mice, fathead minnows, or rainbow trout was preincubated with an IC90 concentration of either paraoxon or malaoxon. The first-order rate constants for both the reactivation and aging of paraoxon-inhibited AChE from rats and mice were significantly greater than those observed for either species of fish. Following malaoxon inhibition, however, rodent AChE reactivated more rapidly but aged more slowly than did the enzyme from minnows. Therefore, the data suggest that compared to rodents, intermittent or continuous exposure of fish to sublethal concentrations of anticholinesterase compounds is more likely to result in a cumulative toxicity owing to the relative irreversibility of AChE inhibition. PMID- 3341040 TI - In vivo distribution of organophosphate antidotes: autoradiography of [14C]HI-6 in the rat. AB - In order to visualize the distribution of HI-6 in the rat after iv administration, autoradiographic experiments were carried out with [14C]HI-6, labeled at the carbon of the carboxamide moiety. Autoradiography clearly confirms penetration of HI-6 into the central nervous system. Considerable radioactivity was found in the cerebrum, the cerebellum, and the choroid plexus. No significant activity was detected in the pontomedullary region or the spinal cord. Peripherally, [14C]HI-6 is observed in large amounts in kidneys, heart, liver, nose, bladder, testes, and marrow-containing bone. The gastrointestinal tract was largely devoid of any radioactivity. The relative absence of HI-6 in the pontomedullary region renders centrally mediated influences of HI-6 on hemodynamic and respiratory parameters less likely. PMID- 3341041 TI - Adverse effects of (15S)-15-methyl-prostaglandin E1 in normal and paraquat exposed rats. AB - Single, daily injections of approximately 1 mg/kg of (15S)-15-methyl-PGE1 (mPGE1), a PGE1 analog, have been reported to inhibit inflammation and to prolong survival in several animal models of local and systemic inflammation. We examined the effect of this dose of mPGE1 on paraquat toxicity in rats. A significant increase in early mortality was identified in mPGE1-treated rats as early as 3 hr following injection of paraquat and appeared associated with increased respiratory effort. Rats given mPGE1 without paraquat also appeared to increase respiratory effort but did not die. Rats killed at 3 hr following injections demonstrated increased lung weights in both paraquat-injected and control animals receiving mPGE1. Although a neutrophilia was identified in these animals, no significant increase in lung lavage neutrophils or albumin was identified. These data suggest that large intermittent doses of a PGE1 analog may adversely affect the respiratory system of normal and injured animals, and will accelerate mortality following exposure to potentially lethal doses of paraquat. PMID- 3341042 TI - Toxicity and distribution of 2-methyl-4-chlorophenoxyacetic acid (MCPA) in developing chick embryos. AB - The toxicity of the herbicide Erbitox E30, a commercial formulation of 2-methyl-4 chlorophenoxyacetic acid (MCPA) containing 28% MCPA as sodium-potassium salt and 72% of unknown ingredients, was tested on chick embryos. Sterile aqueous solutions of MCPA were injected into the air chamber at doses of 0, 1.5, 3.0, 6.0, 9.0, or 10.5 mg/egg on day 0 or on day 4 of incubation. The mortality rate for the embryos treated on day 0 of incubation was high in the first 5 days, low from 5-12 days and again increased by 15 days. The 15-day LD50 was 4.4 mg/egg (95% C.I. 3.7-5.3 mg/egg). HPLC analysis of albumen and yolk showed that concentrations of MCPA in the albumen were detectable at 5 min, highest at 7 days and markedly diminished by 14 days of incubation; a significantly lower concentration of MCPA was found in the yolk throughout the incubation period, except at 14 days when the yolk concentration was 4 times higher than the albumen concentration. At 15 days of incubation, MCPA was evenly distributed in the tissues of the embryo. MCPA was more toxic to 4-day embryos; concentrations above 6.0 mg/egg were lethal to all embryos within the first week of incubation. The 15 day LD50 for treatment on day 4 of incubation was 2.8 mg/egg (95% C.I. 2.5-3.2 mg/egg). The liver was affected by treatment with MCPA, being green in treated embryos. However, histological examination revealed few changes in the liver parenchyma. PMID- 3341043 TI - The absorption of trichloroethylene and its metabolites from the urinary bladder of anesthetized dogs. AB - In order to examine the absorption of trichloroethylene (TRI) and its metabolites from the urinary bladder of dogs, we injected TRI and its metabolites, i.e., chloral hydrate (CH), free trichloroethanol (F-TCE), trichloroacetic acid (TCA) and conjugated trichloroethanol (Conj-TCE), into the urinary bladder of anesthetized dogs, and measured the agents and their respective metabolites in the blood or serum, urine and bile. The percentage of water absorbed from the urinary bladder was 10-20% 2 h after the administration of all substances. The percentage of agents absorbed was 60-70% for the TRI and TCA groups, and 50-60% for the CH, F-TCE and Conj-TCE groups 2 h after administration. The combined urinary and biliary excretion rates of the absorbed materials from the urinary bladder 2 h after administration were 46% for F-TCE, 30% for CH, 6% for Conj-TCE and 0.5-1.0% for TRI and TCA. Urinary re-excretion rates of the total excreted amounts were 65-70% in TRI, CH and F-TCE groups, about 50% in TCA and 99% in Conj TCE group. It is possible that all of the substances administered, particularly F TCE, are metabolized to Conj-TCE in the urinary bladder. PMID- 3341044 TI - Growth in young rats after termination of sodium selenite exposure: studies of growth hormone and somatomedin C. AB - In a previous study we have shown that the growth retarding effect of selenium in infant rats occurs concomitantly with severely reduced growth hormone responses and serum somatomedin C. Furthermore, normal growth may be restored by administration of exogenous growth hormone administration. In the present study we examined the alterations after withdrawal of selenite administration in growth rate, serum growth hormone after GRF 40 injection and serum somatomedin C. Thirty six rats were divided into 3 groups; i.e. controls, rats on continuous selenite treatment from days 21 to 63 of age and a group where selenium was withdrawn on day 42. The first 2 groups grew linearly during the experimental period, the second at a very significantly lower rate. In the third group after cessation of exposure a brief growth spurt occurred followed by a growth rate significantly different from that of the other 2 groups. The reduced GH response to GRF 40 stimulation was normalized 3 weeks after withdrawal, whereas serum somatomedin C remained at the same low level as in those rats on continuous selenite administration. There were other signs of liver lesion at day 42, i.e. elevated ALAT and reduced serum albumin, changes which became insignificant in all 3 groups at the end of the experiment. These results demonstrate that whereas stimulated growth hormone secretion was reestablished 3 weeks after termination of selenium exposure, severely reduced liver somatomedin C production persisted. An improvement in growth rate was also noted, but normal growth rate was not reached 3 weeks after discontinuation of the selenite treatment. PMID- 3341045 TI - Morphological recovery of hippocampal pyramidal neurons in the adult rat exposed in utero to ethanol. AB - Reduced numbers of dendritic spines on the secondary apical dendritic branches and basilar dendrites of CA1 and CA3 pyramidal neurons were observed in ethanol treated rats during embryonic life aged 15 days when compared with age-matched controls. However, differences were no longer present at the age of 90 days. These results suggest that recovery of some morphological parameters of pyramidal hippocampal neurons may occur in rats exposed in utero to ethanol. PMID- 3341046 TI - Response of blood and brain cholinesterase to dermal exposure of bromophos in the rat. AB - Response of cholinesterase to dermal exposure of acute, single and multiple doses of Bromophos in the female rat has been studied. Dose-response studies (50-4000 mg/kg body weight, 24 h exposure) showed that plasma cholinesterase was most sensitive to inhibition in vivo, followed by the brain and erythrocyte acetylcholinesterase. The ID50 values for the in vivo cholinesterase inhibition were 10.1, 576.1 and 1938.0 mg/kg body weight for the plasma, brain and erythrocytes, respectively. In time-course studies after a single sublethal dose of 1000 mg/kg body weight (24 h) of Bromophos, the serum and brain cholinesterase were rapidly inhibited reaching a maximum at 16 h. Recovery was complete in the case of serum at 14 days post-exposure, whereas the brain enzyme was not fully recovered at 21 days. In a subacute study, daily dermal application of 50 mg/kg body weight of Bromophos for 5 and 10 days, resulted in high inhibition of the serum cholinesterase and brain acetylcholinesterase, the former being more marked which was reversible after 10 or 15 days of post-exposure period. Very low levels of dermal exposure of Bromophos (10-50 mg/kg body weight) for 17 days caused pronounced depression of serum cholinesterase which completely recovered in 15 days after cessation of exposure suggesting that the serum cholinesterase could serve as the most sensitive diagnostic indicator of Bromophos exposure. PMID- 3341047 TI - Effects of TCDD-estradiol interactions in three strains of mice. AB - Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and estradiol were studied in three strains of mice: CD-1 and C57B/6 (TCDD sensitive) and DBA/2 (TCDD resistant at lower doses). Immature females were injected with 0-200 ng/kg/day estradiol for 2 weeks, s.c. On days 7, 9, 11, and 13, mice received 10 micrograms TCDD/kg by gavage. Relative uterine weight increased in mice of all three strains treated with estradiol alone. Uterine imbibition was suppressed by TCDD treatment, although this effect was antagonized in a saturable manner by coadministration of estradiol. TCDD induced aryl hydrocarbon hydroxylase (AHH) in liver microsomes of treated mice independent of estradiol dose and strain of mice (the dose of TCDD used was high enough to cause AHH induction in the resistant DBA/2 mice). Treatment of CD-1 mice, but not other strains, with TCDD and estradiol resulted in a decrease in the electrophoretic band of hepatic microsomal proteins comigrating with cytochrome P-450a and epoxide hydrase. PMID- 3341048 TI - Alterations in the thyroids of rats treated for long periods with di-(2 ethylhexyl) phthalate or with hypolipidaemic agents. AB - Treatment of rats for periods of 3 months or longer with the hypolipidaemic drugs clofibrate and fenofibrate or with the plasticiser di-(2-ethylhexyl) phthalate causes alterations in the thyroid. The colloid is shrunken and contains calcium rich inclusions. Electron microscopy shows increases in the number and size of lysosomes, hypertrophy of the Golgi apparatus and dilation of the rough endoplasmic reticulum. These changes are consistent with persistent hyperactivity in the gland. PMID- 3341049 TI - Spatial memory impairment and central muscarinic receptor loss following prolonged treatment with organophosphates. AB - Memory impairment is one of the recurrent complaints of agricultural workers repeatedly exposed to organophosphorus insecticides. In an effort to establish an animal model for such behavioral effects, which would allow studying its underlying biochemical mechanism(s), in this study we evaluated spatial memory in animals following repeated organophosphate exposure. Male Long-Evans rats were given daily i.p. injections of either diisopropylfluorophosphate (DFP; 1 mg/kg/day) or disulfoton (O,O-diethyl S-[2-(ethylthio)ethyl] phosphorodithioate; 2 mg/kg/day) for 14 days. Acetylcholinesterase activity was inhibited 71-77% in the cortex, hippocampus, and striatum of rats treated with DFP, and 73-74% in those treated with disulfoton. Binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cholinergic muscarinic receptors in the same brain areas was reduced 16-28% in organophosphate-treated rats. This decrease was due to a reduction in muscarinic receptor density (Bmax) with no changes in receptor affinity. At the end of the treatment rats were tested for spatial memory using the spontaneous alternation task in a T-maze. Rates of true spontaneous alternation were 64.4, 45.0, and 44.8% in animals which received corn oil, DFP, or disulfoton, respectively (P less than 0.05). These results indicate that prolonged inhibition of acetylcholinesterase caused by repeated organophosphate exposure alters spatial memory functions in rats, as well as causing a loss of muscarinic receptors. Considering the role of the cholinergic system in cognitive processes, these biochemical alterations could be related to the observed behavioral changes and may offer a potential explanation of the memory impairment reported by workers chronically exposed to organophosphates. PMID- 3341050 TI - Probenecid-induced protection against acute hexachloro-1,3-butadiene and methyl mercury toxicity to the mouse kidney. AB - Male Swiss OF1 mice received a single oral dose of either 80 mg/kg hexachloro-1,3 butadiene (HCBD) or 40 mg/kg methyl mercury (MeHg). Examination of cryostat kidney sections stained for alkaline phosphatase (APP) revealed damage to about 50% of the proximal tubules after 8 h. Treatment with the organic anion transport inhibitor probenecid (i.p., 3 x 0.75 mmol/kg) did not have any renal effect in normal mice but reduced the number of damaged tubules by 80 and 90% in mice treated with HCBD and MeHg respectively. The results support the conclusion that the toxicity of HCBD and MeHg to the mouse kidney is related to a probenecid sensitive transport process. It cannot be stated from the present investigation whether the inhibition nephrotoxicity data are related to classic organic anion secretion by the kidney. PMID- 3341051 TI - The effect of mono-(2-ethylhexyl) phthalate and other phthalate esters on lactate production by Sertoli cells in vitro. AB - Sertoli cells produce lactate and pyruvate as energy substrates for the developing germ cells in the testis. Since the Sertoli cells are thought to be the initial target for phthalate esters causing testicular atrophy, the effect of some phthalates on lactate and pyruvate production by primary Sertoli cell enriched cultures was studied. Mono-(2-ethylhexyl) phthalate (0.1-200 microM) produced a concentration-dependent stimulation of lactate, but not pyruvate production over a 24 h treatment period and an increase in the ratio of lactate/pyruvate concentration in the culture medium. Di-(2-ethylhexyl) phthalate and 2-ethylhexanol (200 microM) had no such effects. Other phthalate monoesters known to cause testicular atrophy also increased Sertoli cell lactate production and the lactate/pyruvate ratio, whereas monoesters not associated with testicular damage in vivo had no such effects. The results suggest that loss of germ cells in phthalate-induced testicular atrophy is not due to inhibition of energy substrate production by the Sertoli cells and that stimulation of lactate production may be a useful in vitro marker for phthalate esters and related compounds that cause testicular injury. PMID- 3341052 TI - Metabolism of dichloromethane and the subsequent binding of its product, carbon monoxide, to cytochrome P-450 in perfused rat liver. AB - The interaction of cytochrome P-450 and dichloromethane (DCM) was investigated spectrophotometrically in the perfused rat liver. DCM bound to cytochrome P-450 and showed a type I spectral change, with a peak at 450 nm. The peak at 450 nm was developed by addition of exogenous carbon monoxide (CO) to the perfusate. By examining the pattern of the spectral change, we concluded that CO formed during DCM metabolism by cytochrome P-450 bound to cytochrome P-450 in the perfused liver. PMID- 3341054 TI - Hyperphalangeal bones induced in rat pups by maternal treatment with nifedipine. AB - Hyperphalangeal bones were found in postnatal rat pups of mothers treated with nifedipine during pregnancy. The anomaly occurred only at the region between the middle and distal phalanges of the 3rd and 4th fingers and toes. The critical periods of the anomaly were days 13 and 14 of pregnancy for the fingers, and days 14 and 15 of pregnancy for the toes. The incidences were dose-related, being more than 90% in both fingers and toes at a single dose of 150 mg/kg, and even more marked at the 4th digits than at the 3rd digits. Neither right/left difference nor sex difference was manifested in the incidence of the anomaly. PMID- 3341053 TI - Effects of urinary crystals induced by acetazolamide, uracil, and diethylene glycol on urinary bladder carcinogenesis in N-butyl-N-(4-hydroxybutyl)nitrosamine initiated rats. AB - In order to examine the promoting effect of urinary crystals on urinary bladder carcinogenesis, acetazolamide, uracil, and diethylene glycol, all of which have been reported to cause urinary crystals or calculi, were administered to male F344 rats for 32 weeks after pretreatment with 0.05% N-butyl-N-(4 hydroxybutyl)nitrosamine (BBN) for 4 weeks. A marked increase in urinary crystals was observed in acetazolamide-treated rats and a slight increase in crystals was observed in uracil- and diethylene glycol-treated rats. Histological examination of the urinary bladder revealed that the BBN-acetazolamide treatment resulted in a higher incidence of carcinoma than BBN-control. Uracil and diethylene glycol did not cause any significant difference compared to the control. Promoting effects by urinary crystals were not clearly shown in the present experiment and, therefore, urinary crystals appear to play a very limited role, if any, in urinary bladder carcinogenesis. PMID- 3341055 TI - Effects of type I and type II pyrethroids on the startle response in rats. AB - The effects of type I and type II pyrethroids on the acoustic startle response of male Wistar rats were studied in three experiments. Pyrethroids were administered p.o. in 0.2 ml corn oil. In Expt. 1, techn. cis-permethrin (0, 30, 60, 90 mg/kg) and techn. cis, trans-cypermethrin (0, 60, 90, 120 mg/kg) increased startle in a dose-dependent way, whereas overt behavior and habituation of the startle response were not affected. In Expt 2, NAK 1901 (0, 1, 2.5, 4 mg/kg) enhanced startle amplitudes dose dependently and deltamethrin (0, 2, 4, 6 mg/kg) had no effect on startle. After both deltamethrin and NAK 1901 toxic signs increased dose dependently but an effect on potentiation of the startle reflex was not found. In Expt. 3, deltamethrin (0, 2, 4, 6 mg/kg) was administered and the highest dose attenuated startle amplitudes significantly, whereas toxic signs increased dose dependently. Deltamethrin had no effect on habituation of the startle response. It is concluded that type I pyrethroids increase the amplitude of the startle reflex; this effect does not depend on the presence of overt signs of toxicity. Type II pyrethroids have dissimilar effects on startle. Results are discussed suggesting that the effects of type II pyrethroids on startle amplitude are mediated by an indirect metabolic effect and a direct effect at the site of the muscle. PMID- 3341056 TI - Effect of maternal selenium deficiency on the teratogenicity of methylmercury. AB - The teratogenicity of methylmercury was examined in selenium-deficient and selenium-sufficient mice of the ICR strain. A single oral dose of 75 mumol/kg of methylmercuric chloride (MMC) on day 10, 11 or 12 of gestation caused similar incidences of a cleft palate in the selenium-deficient and selenium-sufficient mice. The treatment on day 11 led to the highest incidence of a cleft palate in both groups. These results suggest that a maternal selenium deficiency has no effect on the incidence or on the critical gestational period for an MMC-induced cleft palate. PMID- 3341057 TI - Intestinal transfer of sodium [14C]taurocholate in streptozotocin-treated rats. AB - The effect of streptozotocin (SZ) administration on sodium [14C]taurocholate (TC) transmural transfer was studied in the everted rat ileum. The excretion of fecal bile acids was also studied in living rats injected with that compound. The viability of the preparation used for the in vitro experiments was evaluated by light microscopy and by the rate of glucose uptake by tissue from the mucosal fluid. The results obtained showed that TC transfer to the serosal fluid was impaired after 24 h of SZ injection, as well as the active transport observed in control preparations. The amount of TC accumulated in the intestinal tissue was also diminished. In addition, total ATPase activity of tissue was decreased, and intracellular electrolyte concentration was altered. Therefore, a slower saturation of binding sites could be responsible for the effects of SZ on TC tissue accumulation, and a decreased ATPase activity for the impairment of the TC concentrative transport system. The results observed in vitro were supported by data in vivo because fecal bile acid excretion was significantly diminished in SZ treated rats. PMID- 3341058 TI - Infection with hepatitis delta and human immunodeficiency viruses among hemophiliacs in Japan. AB - Two hundred two patients with hemophilia, dependent solely on imported coagulation factor concentrates, were tested for markers of hepatitis B virus infection, antibody to hepatitis delta virus (anti-HD), and antibody to human immunodeficiency virus (anti-HIV). Nine carriers of hepatitis B surface antigen (HBsAg) were identified. Six (66.7%) of them were positive for anti-HD, a prevalence much higher than that in HBsAg carriers without hemophilia in Japan (1/113 or 0.9%, p less than 0.001). Anti-HIV was found in 96 (47.5%), in sharp contrast to the low prevalence (0/1205) in apparently healthy blood donors (p less than 0.001). These results implicated imported plasma products in the transmission of both delta and human immunodeficiency viruses to hemophiliacs. An efficient method for the sterilization of plasma products is warranted to prevent exposure of hemophiliacs to the accompanying pathogenic viruses. PMID- 3341059 TI - Inactivation of virus in blood products. PMID- 3341060 TI - A rapid method for harvesting autologous red cells from patients with hemoglobin S disease. AB - Red cells from patients with sickle cell disease (HbSS and HbSC) are more resistant to lysis in hypotonic NaCl solutions than normal (HbAA) red cells. Taking advantage of this inherent resistance to osmotic stress, patient red cells (HbSS or HbSC) were rapidly isolated from donor red cells (HbAA or HbAS) by washing with hypotonic (0.3%) NaCl. The hypotonic method of washing provides a previously unavailable means for obtaining autologous HbSS or HbSC red cells from samples containing transfused donor red cells. Once isolated, these red cells can be used for phenotyping, autoadsorption, or evaluation of positive direct antiglobulin tests. PMID- 3341062 TI - Hypergammaglobulinemia can be associated with a positive direct antiglobulin test, a nonreactive eluate, and no evidence of hemolysis. AB - To determine the cause of a positive direct antiglobulin test (DAT), blood banks routinely perform serologic tests on eluates prepared from DAT-positive red cells. Negative eluates traditionally have been suspected to be associated with drug reactions. This report confirms that the most frequent cause of a positive DAT and a nonreactive eluate is hypergammaglobulinemia. The results of 74 patient samples with positive DATs were analyzed retrospectively. Eluates prepared from the red cells of 54 patients (72.9%) reacted; eluates from 20 patients (27.1%) did not react. This latter group had identical serologic and clinical findings, suggesting that they made up a homogeneous group. In particular, the patients had a positive DAT, a negative indirect antiglobulin test, and a negative eluate; an increased serum concentration of IgG; and no evidence of hemolysis. In a subsequent study, DATs were performed prospectively on red cells from 44 consecutive patients with elevated serum IgG levels. The serum IgG concentration was highest in the three patients whose red cells had a positive DAT. The DAT also became positive in two patients treated with high-dose intravenous gammaglobulin (IV IgG). These studies indicate that a negative eluate from red cells with a positive DAT, a common serologic finding, is often caused by hypergammaglobulinemia. The authors postulate that IgG binds nonspecifically to the red cells because of the hypergammaglobulinemia. PMID- 3341061 TI - Standardization of papain reagents by measurement of active sites using a synthetic inhibitor, E-64. AB - L-trans-epoxysuccinyl-leucylamido (4-guanidino) butane (E-64) reacts rapidly and irreversibly in a one-to-one ratio with the active site of papain, causing complete inhibition of the enzyme. After the addition of various concentrations of E-64 to a papain preparation, the residual enzyme activity can be measured using an azoprotein technique. The molarity of E-64 required to cause complete inhibition of papain activity is equal to the molarity of papain-active sites. Preparations of papain from various sources were assayed for protease activity by hydrolysis of azoalbumin using several variants of the basic technique and also by hydrolysis of azocasein. For each variant of azoprotein assay procedure, the active sites of the papain were measured using E-64. All variations of the azoprotein technique yielded similar estimates of the active site molarity of the papain preparations, whereas the azoprotein assay results alone showed wide variation. Quantitation of the active-site molarity of various papain preparations using E-64 correlated with serologic efficacy. PMID- 3341064 TI - Combined plasma exchange and intravenous gammaglobulin in the treatment of patients with refractory immune thrombocytopenic purpura. AB - Plasma exchange (PE) and intravenous gammaglobulin (IVGG) are potentially effective therapies in immune thrombocytopenic purpura (ITP). In this study, eight patients refractory to IVGG and to prednisone were treated with a protocol of combined PE and IVGG therapy using a single PE on each of 3 consecutive days, followed by 2 consecutive days of IVGG at 1 g per kg. Four of the eight patients responded to the combined therapy with a mean peak platelet count of 132,000 per microliter (range, 74,000 to 225,000/microliter). Responses lasted approximately 2 weeks. These four patients were among the five who had initially responded to IVGG before becoming refractory; none of the three patients without an initial response to IVGG responded to the combined therapy. Age, duration of disease, and splenectomy status did not appear to be related to response to the combined therapy. Two patients began maintenance treatment (1 PE followed by 1 g/kg IVGG on the same day), but both became unresponsive after three treatments. PE combined with IVGG may be a useful treatment for some patients with refractory ITP who have uncontrollable bleeding or require major surgery. The development of resistance to IVGG effect may be mediated by an increase in the level of antiplatelet antibodies. PE, by lowering antiplatelet antibody levels, may then allow IVGG infusion to be effective again in elevating the platelet count. PMID- 3341063 TI - Xanthone additives for blood storage that maintain its potential for oxygen delivery. I. 2-Hydroxyethoxy- and 2-ethoxy-6-(5-tetrazoyl) xanthones in citrate phosphate-dextrose-adenine (CPDA-1) blood. AB - Two xanthones, 2-hydroxyethoxy-6-(5-tetrazoyl) (BW A440C) and 2-ethoxy-6-(5 tetraozyl) (BW A827C), are members of a chemical series tested in vitro as potential additives to citrate-phosphate-dextrose-adenine (CPDA-1) medium for blood storage. P50 was maintained in the presence of these compounds during 42 days' storage by a partial maintenance of 2,3 diphosphoglycerate (2,3 DPG) and by a direct effect on hemoglobin previously reported for BW A827C. Red cell 2,3 DPG levels for BW A440C (n = 5), BW A827C (n = 5), and control (n = 6), respectively, were 3.38 +/- 0.47, 3.44 +/- 0.25, and 1.20 +/- 0.10 mM +/- SEM on day 7; 1.16 +/ 0.13, 1.52 +/- 0.37, and 0.16 +/- 0.02 mM on day 21; and 0.67 +/- 0.09, 0.61 +/- 0.08, and 0.06 +/- 0.006 mM on day 42. Red cell adenine triphosphate levels at the same time intervals were 1.84 +/- 0.09, 1.46 +/- 0.18, and 2.11 +/- 0.04 mM; 2.10 +/- 0.05, 2.07 +/- 0.17, and 2.13 +/- 0.05 mM; and 1.42 +/- 0.13, 1.37 +/- 0.13, and 1.38 +/- 0.06 mM, respectively. The degree of hemolysis was less with the addition of the compounds, and the methemoglobin formation, plasma Na+ and K+, and lactate production were unaffected by the compounds. PMID- 3341065 TI - Changes in hospital component therapy in response to reduced availability of whole blood. AB - The effects of a systematic reduction of whole blood (WB) availability on transfusion practice were studied at a large university-affiliated community hospital from 1978 through 1985. The reduction in WB availability was part of a planned statewide shift in blood procurement and processing from hospitals' individual blood banks to a new statewide blood center. Hospital WB use declined 96 percent, from 3400 to 109 units annually, with a net addition of more than 3000 units of plasma to the statewide stocks. A large increase in the use of other blood components occurred when WB was withdrawn, but this use fell sharply in 1984 and 1985, despite the continued relative unavailability of WB. Analysis of individual hospitals' services showed that increases in the use of packed red cells were distributed across all the services that frequently use red cell transfusions. However, a disproportionate rise and then fall in the use of fresh frozen plasma and platelets for cardiovascular operations were observed. The data suggest that education and more conservative transfusion practices are reducing the use of blood components despite continued restricted availability of WB. PMID- 3341066 TI - Evaluation of a centrifugal blood cell processor for washing platelet concentrates. AB - A semiautomated saline wash procedure using a blood cell processor was evaluated as a technique for removing plasma from platelet concentrates. In vitro studies demonstrated 92 to 99.6 percent (mean, 96%) removal of total plasma protein (n = 30) with 84 to 97 percent (mean, 90.8%) platelet recovery (n = 28) in post-wash units. Post-wash pH values changed by +0.2 to -0.86 (mean, -0.47) (n = 30); the level of recovery from hypotonic shock was 69 to 97 percent (mean, 86%) (n = 11) of pre-wash units; weighted morphology scores decreased from a mean of 248 to 223 (n = 9). Aggregation response to arachidonic acid, collagen, and adenosine diphosphate plus epinephrine showed essentially no change following the wash procedure, and electron microscopy demonstrated slight morphologic alteration. Autologous platelets labeled with indium-111 demonstrated 43 +/- 20 percent recovery (n = 11) for washed units, compared to 41 +/- 10 percent for control unwashed units (n = 5); mean survivals were 140 +/- 41 hours (n = 11) for washed platelets and 185 +/- 28 hours for unwashed units (n = 5). Thirteen alloimmunized patients receiving 55 washed platelet concentrates demonstrated a mean 1- to 4 hour corrected count increment of 3.99 X 10(3) per microliter, compared to 3.02 X 10(3) per microliter for 77 unwashed platelet units given to the same patients. This study documents that platelet concentrates maintain viability and efficacy following a semiautomated saline wash method using the Cobe 2991 Blood Cell Processor, a technique that may be helpful for patients who require plasma depleted platelet transfusions. PMID- 3341067 TI - Recovery and survival in vivo of platelet concentrates prepared with prostaglandin E1. AB - In follow-up to previous studies showing that stimulators of adenylate cyclase inhibit the activation of platelets in platelet concentrates (PC), the posttransfusion recovery and survival of autologous platelets prepared and stored after the addition of prostaglandin E1 (PGE1) to platelet-rich plasma at a concentration of 1.3 X 10(-8) M were investigated. Six normal subjects were studied on the two occasions, using PC stored with and without PGE1 and radiolabeling with 51Cr. The mean recovery of platelets prepared with PGE1 (35.2 +/- 8.1%) was significantly lower (p less than 0.013) than that of routinely prepared platelet concentrates (46.3 +/- 9.4%). The mean life-spans of platelets prepared with and without PGE1 were 7.1 +/- 0.4 and 6.2 +/- 1.0 days, respectively (p = NS). Despite its ability to inhibit the activation of platelets during concentration and storage, prostaglandin E1 appears to reduce posttransfusion recovery of platelets significantly in this experimental model and cannot be recommended at this time as an adjunct for PC preparation. PMID- 3341068 TI - Prevalence of Babesia antibody in a selected blood donor population. AB - Human babesiosis, a parasitic disease transmitted by the tick, Ixodes dammini, was confined previously to limited areas of the northeastern United States. It is a rare but potentially life-threatening complication of transfusion. Red cells and platelets prepared from asymptomatic donors have been implicated in transfusion-transmitted cases. More cases of babesiosis are being reported as the range of the vector expands in the United States. Blood donors from an endemic area were tested for antibody to Babesia microti during the summer. Only 3.7 percent of the 779 donors were seropositive, compared with 4.7 percent (p greater than 0.05) of donors from a nonendemic area. An epidemiologic survey of seropositive and matched seronegative controls demonstrated no significant differences that would assist in screening donors. PMID- 3341069 TI - Iron stores in remunerated blood donors as evaluated by plasma ferritin levels. AB - This study was undertaken to investigate body iron stores in so-called remunerated blood donors as well as to evaluate the sensitivity of hemoglobin determination in detecting iron deficiency in two populations of blood donors. The authors studied 522 male donors who were divided into three groups: Group I, first-time volunteer donors with hemoglobin levels greater than or equal to 13 g per dl; Group II, remunerated donors with hemoglobin levels greater than or equal to 13 g per dl; and Group III, remunerated donors rejected because their hemoglobin levels were less than 13 g per dl. Iron stores were evaluated with an enzyme-linked immunosorbent assay for plasma ferritin. In Group I, 4.5 percent were iron-deficient with a mean ferritin value of 55.3 ng per ml; in Group II, 59.7 percent were iron deficient with a mean ferritin level of 17.4 ng per ml, and in Group III, 82.5 percent were iron-deficient and the mean ferritin level was 8.4 ng per ml. The last values represent the highest percentage of iron deficiency and the lowest mean ferritin value thus far reported. In Group I, hemoglobin determination had a sensitivity of 95 percent in detecting iron deficiency, but in Group II had only 40 percent sensitivity. These results indicate that a more accurate and reliable test, such as a plasma or serum ferritin determination, may be necessary to detect iron deficiency in blood donors when they donate more than five times per year, particularly those who are remunerated. PMID- 3341070 TI - The value of 10-minute posttransfusion platelet counts. AB - Monitoring of platelet counts 1 hour after transfusion has become standard practice in most centers. In this study, platelet counts obtained 10 and 60 minutes after 48 platelet transfusions were compared. There was a close, linear relationship (r = 0.98) between these values over a wide range of posttransfusion counts, indicating rapid equilibration of transfused platelets. Ten-minute posttransfusion samples are easier to obtain and are convenient for both patients and medical staff. PMID- 3341071 TI - Successful conservative management of thrombocytopenia in adult hemophiliacs. AB - Hematologic abnormalities, including thrombocytopenia, have been reported in persons with acquired immune deficiency syndrome and in hemophiliacs. Seven of 92 adult hemophiliacs followed in a comprehensive hemophilia center developed mild to moderately severe thrombocytopenia in 1983. All had benign courses. None required therapy for thrombocytopenia, although several had increased cutaneous bleeding. Infection with human immunodeficiency virus may be important in the pathogenesis of these patients' thrombocytopenia as it has been in that of homosexual men. PMID- 3341072 TI - Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia. AB - The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia. PMID- 3341074 TI - HBV DNA in blood donors. PMID- 3341073 TI - A severe transfusion reaction associated with anti-EnaTS in a patient with an abnormal alpha-like red cell sialoglycoprotein. AB - A 71-year-old woman (Ped) received 3 units of red cells (RBCs), compatible by the indirect antiglobulin test but strongly (4+) incompatible by direct agglutination at 37 degrees C. The next day, her plasma hemoglobin was 1252 mg percent and the direct antiglobulin test (DAT) was weakly positive (IgG and C3). Less than 5 percent of the transfused cells could be detected 48 hours posttransfusion. Her clinical condition deteriorated and renal failure developed. The patient died of pulmonary embolism. Her serum contained a strong (4+) IgM agglutinin and a weakly reactive (microscopically positive) IgG antibody, with anti-EnaTS specificity. EnaFS and EnaTS antigens were severely depressed or absent from the patient's RBCs; the ficin-resistant Ena antigen (EnaFR) appeared to be present. Pretransfusion RBC sialic acid level was 53 +/- 2 percent of normal. The patient's RBC membranes were shown to contain sialoglycoproteins beta and delta by sodium dodecyl sulphate polyacrylamide gel electrophoresis with periodic acid Schiff's base staining, with weak staining of components in the regions corresponding to alpha, alpha 2 and alpha delta. The nature of these components was not identified, but their presence suggested that the patient's RBCs expressed a previously undescribed sialoglycoprotein alpha variant. PMID- 3341076 TI - Level of probability in antibody identification. PMID- 3341075 TI - Tn-polyagglutinable donors and the antiglobulin compatibility test. PMID- 3341077 TI - An example of anti-S enhanced at acid pH. PMID- 3341078 TI - Two cases of transfusion-transmitted malaria (TTM) in the UK. PMID- 3341079 TI - HIV infection in polytransfused patients with hemoglobinopathies in France. PMID- 3341080 TI - On the inheritance of Er and the frequency of Era. PMID- 3341081 TI - Anti-LKE in a pregnant woman. PMID- 3341082 TI - Gastric cancer in Nigeria. PMID- 3341083 TI - Short-segment Hirschsprung's disease. A ten-year review from Zaria, Nigeria. PMID- 3341084 TI - Bacteriology of prostatectomy patients' urine in a drug-abused community. PMID- 3341085 TI - Paediatric inguinoscrotal surgery in a district hospital. PMID- 3341086 TI - Family planning linked to an obstetric service. PMID- 3341087 TI - Causes of congenital and acquired total sensorineural hearing loss in Ghanaian children. PMID- 3341088 TI - Planning PHC for a community: a baseline survey provides essential data. PMID- 3341089 TI - Utilizing education infrastructure for primary health care. PMID- 3341091 TI - Oral regulated feeding and hydration. PMID- 3341090 TI - Why cholera still takes lives in rural Bangladesh. Study of an epidemic. PMID- 3341092 TI - Scarabiasis. PMID- 3341093 TI - Psychotropic polypharmacy in Nigeria. The danger can be avoided and cost reduced. PMID- 3341094 TI - Systemic complication of intracavernous papaverine injection in patients with venous leakage. AB - Intracavernous papaverine injection is often used in the diagnosis and treatment of male impotence. Prolonged erection and/or priapism are well known local complications. Systemic side-effects characterized by discomfort and dizziness due to rapid escape of the drug into the vascular circulation also can occur in patients with venous leakage. Thus, venous leakage should be ruled out prior to intracavernous injection of papaverine in the treatment of impotence. Ligation of the deep dorsal vein and the small veins around the tunica albuginea will lessen the problem. PMID- 3341095 TI - Instability and rotation of silver silicone penile prosthesis. AB - Four cases of a similar complication in patients who have had the Jonas silver silicone prosthesis implanted are reported. The patients complain of instability and rotation of the prosthesis to a position that stands out from the body, no matter what the initial position of the prosthesis. The rotation causes difficulty with coitus. The explanation is one of a manufacturing and not a surgical defect. PMID- 3341096 TI - Characterization of secretion pattern of human prostatic acid phosphatase: a reassessment. AB - The daily variation of serum levels of prostatic acid phosphatase (PAP) determined by the Roy enzymatic method was investigated in 10 patients with metastatic prostatic cancer and in 10 patients without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis of the mean PAP levels at the four sampling times in both groups of patients demonstrated no evidence of circadian or diurnal rhythmic variation. Prostate cancer patients did show significantly greater variability in daily PAP than patients without prostatic disease, although a distinct pattern of secretion was not observed in either group. These results underscore the potential inaccuracy of the use of single determination of serum PAP as a parameter of response in patients with metastatic prostatic cancer and in the staging of patients with clinically localized prostatic malignancy. Evaluation of trends of PAP levels over time, however, continues to play a major role in the assessment and management of patients with prostatic carcinoma. PMID- 3341097 TI - Flexible cystoscopy in surgical repair of traumatic urethral strictures in children. AB - Flexible cystoscopy via a suprapubic cystostomy tract was utilized to locate the proximal segment of a complete traumatic disruption of the bulbar urethra secondary to a pelvic fracture. With the fiberoptic light of the instrument visible in the perineum, the proximal urethra was easily and safely dissected free from the enveloping fibrotic scar tissue and a simple one-stage urethroplasty performed. The patient is voiding normally eight months postoperatively. PMID- 3341099 TI - Approach for treatment of subcoronal meatus with excessively deep glanular groove. AB - We report on 9 children with subcoronal meatus and an excessively deep glanular groove who underwent a simple surgical repair. All the procedures were done on an outpatient basis, and there was no urinary diversion. The surgical results have been satisfactory, with no fistula formation, or urethral or meatal stenosis. The technique described is useful in selected cases. PMID- 3341098 TI - Ketoconazole therapy for hormonally refractive metastatic prostate cancer. AB - Twenty-two patients who had progressive metastatic prostatic carcinoma (Stage D2) despite androgen-deprivation therapy (bilateral orchiectomy, 10 cases; bilateral orchiectomy followed by diethylstilbestrol, 7 cases; diethylstilbestrol, 3 cases; combined megestrol acetate and low-dose estrogen, 2 cases) were treated with ketoconazole. Of 19 evaluable patients, 2 (11%) achieved a partial response (for 6 and 8 months) and 7 others (37%) achieved stabilization of disease (for periods of 3-8 months). Of 16 patients in whom pain was a prominent clinical feature, 13 (81%) noted improvement in pain for periods of one to eight months (median 3 months). We conclude that ketoconazole is a useful addition to our current armory for management of patients with metastatic prostatic cancer resistant to prior hormonal therapy. PMID- 3341100 TI - Polyorchidism and testicular torsion. AB - Presented is a case of a young man with polyorchidism and traumatic testicular torsion. PMID- 3341101 TI - Bilateral single ectopic ureter. AB - A case of single bilateral ureteral ectopia is presented. Patient underwent bilateral ureteral reimplantation with right ureteral tailoring, with a satisfactory result. PMID- 3341103 TI - Spontaneous renocolic fistula secondary to calculous pyonephrosis. AB - A rare case of spontaneous renocolic fistula is described, and the literature is reviewed. PMID- 3341102 TI - Pelvic fibrous mesothelioma with obstructive symptoms. AB - A case report of a fifty-eight-year-old man with complaints of urinary obstructive symptoms and constipation is presented. At laparotomy the patient was found to have a large pelvic mass elevating the bladder and prostate which proved to be a fibrous mesothelioma. A review of peritoneal mesotheliomas is presented. PMID- 3341104 TI - Renal cholesteatoma. AB - Renal cholesteatoma is being reported more frequently in the literature. A case with a twenty-year documented history is presented, together with observations on differential diagnosis. PMID- 3341105 TI - Medullary sponge kidney and hyperparathyroidism. AB - Medullary sponge kidney (MSK), parathyroid adenoma, renal cell carcinoma, and renal-leak hypercalciuria coincided in 1 female patient. Renal-leak hypercalciuria was not corrected by removal of a parathyroid adenoma. Since the patient had renal tubular acidosis (RTA), alkali treatment was conducted and resulted in the correction of hypercalciuria. Renal cell carcinoma eventually developed and MSK was confirmed histologically. This case suggests that MSK and primary hyperparathyroidism occurred independently. PMID- 3341106 TI - Technique for improving vision during flexible nephroscopy. PMID- 3341107 TI - Technique for retrograde ureteral stone displacement. PMID- 3341108 TI - Prevention of hematoma during artificial erection. PMID- 3341109 TI - Liposarcoma of spermatic cord. AB - Liposarcoma of the spermatic cord is a rare tumor. Most are of a low-grade malignancy, and treatment is wide local excision with radical orchiectomy. At present there is no clear indication for chemotherapy. Because recurrence, especially local recurrence, is a possibility, periodic followup is necessary. Local recurrences are treated with repeat wide local excision and radiotherapy. PMID- 3341110 TI - Nuclear magnetic resonance imaging in detecting and staging prostatic cancer. AB - Thirteen patients were examined for grade, stage, and extent of their prostatic cancer, utilizing nuclear magnetic resonance imaging (MRI) and clinical workup for metastases. Of these 13 patients, 12 had known prostatic cancer proved by needle biopsy or by pathologic examination of transurethral prostatectomy tissue. Five of these patients underwent radical surgery allowing further correlation of clinical findings and MRI data with the surgical pathologic findings. MRI of the prostate was found to be a sensitive modality in detecting prostatic carcinoma and showing extension of disease in some cases. Also, in some cases it was not always possible to differentiate between prostatic carcinoma and benign prostatic hyperplasia with MRI. PMID- 3341111 TI - Magnetic resonance imaging of renal oncocytoma. AB - Two cases of renal oncocytoma studied by magnetic resonance imaging (MRI) suggest that this new imaging modality may prove useful in the preoperative diagnosis of oncocytoma and its differentiation from renal cell carcinoma. PMID- 3341112 TI - Agrobacterium-mediated infectivity of cloned digitaria streak virus DNA. AB - A monomeric clone of double-stranded DNA synthesized in vitro DNA of the geminivirus Digitaria streak (DSV) was subcloned as a tandem dimeric unit into a binary vector of Agrobacterium tumefaciens, creating a plasmid pDS2. Inoculation of digitaria sanguinalis with A. tumefaciens carrying pDS2 resulted in viral infection. The symptoms, virus particles, and DNA forms obtained were indistinguishable from those of a natural DSV infection of D. sanguinalis. Inoculations have also induced infections in Zea mays and Avena sativa. The sequence of the Agrobacterium-mediated infectious clone of DSV has been determined. PMID- 3341113 TI - Host range control of cauliflower mosaic virus. AB - Studies with recombinant genomes of cauliflower mosaic virus (CaMV) strains D4, CM1841, and Cabb-B have shown that a host range determinant of CaMV is encoded within the first half of region VI, a gene which codes for P62, an inclusion body protein. In order to further study the host specificity of CaMV, a fourth CaMV strain, W260, was chosen that has a host range that is intermediate between D4 and CM1841. To determine which portion of the W260 genome controls systemic spread, recombinant viruses made between this strain and CM1841 and D4 were tested for their ability to systemically infect several solanaceous plants (Datura stramonium, Nicotiana edwardsonii, and Nicotiana bigelovii). The first half of gene VI specified the type of local lesions and systemic spread of recombinant strains in D. stramonium. In N. edwardsonii, it was found that the first half of gene VI controlled the type of local lesion formed but systemic spread was dependent on the whole of gene VI. In N. bigelovii the number of genes that determined systemic spread of CaMV varied with the strain of CaMV. Systemic spread of D4 in N. bigelovii was dependent on the first half of gene VI. In contrast, systemic spread of W260 in the same host was dependent on the whole of gene VI and another locus which mapped within genes I-V. Consequently, it appears that other viral proteins may interact with P62 or that P62 may function well in some hosts only in compatible forms of other viral proteins. PMID- 3341114 TI - An unusual virus from the parasitic wasp Cotesia melanoscela. AB - Certain strains of the braconid parasitoid Cotesia melanoscela carry two different viruses within their ovaries, one of which (here designated CmV2) is apparently not a polydnavirus. Virus replication occurs in the ovarian calyx and in some other tissues of both male and female parasitoids; as yet, no replication has been observed in the testis, however. In addition, CmV2 is one of only two parasitoid viruses known to replicate in host insect larvae, and we not show that this virus is also capable of replicating in vitro; the virus is nevertheless nonpathogenic for gypsy moth larvae. The virus is not transmissible per os, either to host animals or to larvae of parasitoid strains lacking it. CmV2 is stably maintained within strains carrying it apparently by a vertical transmission mode involving the maternal line; transmission via the male germ line could not be demonstrated. While purification of the virus was not achieved, preliminary work allows us to suggest the genome consists of a single double stranded DNA molecule of approximately 125 kb. PMID- 3341115 TI - Cloning and generation of a genetic map of bacteriophage N4 DNA. AB - Analysis of coliphage N4 development has been hindered by the lack of a genetic map. Conventional methods of complementation and recombination have been inadequate because N4 shows very high levels of recombination, which are independent of the host recombination system. We have cloned restriction fragments of the 72-kb genome of N4 and have used these clones to rescue a collection of suppressor-sensitive and temperature-sensitive mutants. After mutations were localized to a small region by marker rescue, complementation groups were defined. In this way several functions essential for transcription and replication have been mapped. Finally, a nonessential 6-kb region of the N4 genome has been identified by characterizing phage deletions isolated after heat and citrate treatment of virions. PMID- 3341116 TI - Phage T4 DNA codes for two distinct 10-kDa proteins which strongly bind to RNA polymerase. AB - Radioactive proteins have been synthesized in vitro from a coupled transcription translation system primed with bacteriophage T4 DNA. The labeled proteins were chromatographed on RNA polymerase-Sepharose affinity columns in order to identify a protein which comigrates with the 10-kDa anti-sigma subunit of T4-modified RNA polymerase. When we primed the in vitro system with specific restriction fragments of T4 DNA, we found that there seemed to be two widely separated genes which code for this protein. The products of these two genes were compared by two dimensional electrophoresis; they were found to have different charges, even though they had the same molecular weight and strong affinity for RNA polymerase. One of these proteins exists in a form which has the same charge as the 10-kDa subunit isolated from purified T4-modified RNA polymerase. We report a preliminary mapping experiment within the 22.5-kb fragment harboring this gene. PMID- 3341117 TI - Selection for accelerated penetration in cell culture coselects for attenuated mutants of Venezuelan equine encephalitis virus. AB - Previous studies with Sindbis virus (SB) suggested that a single point mutation in glycoprotein E2 (serine 114 to arginine 114) conferred three phenotypic alterations: attenuation in neonatal mice, accelerated penetration of cultured cells, and efficient neutralization by two E2-specific monoclonal antibodies (Davis, Fuller, Dougherty, Olmsted, and Johnston (1986) Proc. Natl. Acad. Sci. USA 83, 6771-6775). Moreover, selection for rapidly penetrating mutants of SB coselected for attenuation in vivo, indicating that a domain of SB E2 which influences penetration in culture overlaps an E2 domain which influences pathogenesis (Olmsted, Meyer, and Johnston (1986) Virology 148, 245-254). To test the possibility that overlapping penetration and pathogenesis domains exist in other alphaviruses, the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus (TRD-VEE) was serially passed in baby hamster kidney (BHK) cells under a stringent selective pressure for accelerated penetration. Isolates were biologically cloned from the first through the fourth passages and were characterized as to penetration time course in BHK cells and virulence in adult mice following intraperitoneal inoculation. Twenty-two of the 27 isolates segregated into two major categories: slowly penetrating and virulent (like the TRD-VEE parent) and rapidly penetrating and avirulent. Mice which received the avirulent mutants were positive for anti-VEE neutralizing antibody and were refractory to challenge with TRD-VEE. Of the seven mouse avirulent mutants, two also were attenuated in hamsters, indicating the presence of at least two genetic loci at which mutations may influence both pathogenesis and penetration. PMID- 3341118 TI - Organization and interviral homologies of the coat protein gene of white clover mosaic virus. AB - The sequence of 1612 nucleotides of the 3'-terminal region of white clover mosaic virus (WCIMV) has been determined from cDNA clones. The viral sense RNA contains four open reading frames of Mr 20,684, Mr 7219, Mr 12,989, and at least Mr 17,000. The latter begins 5' to the sequence determined. The amino acid sequence of the open reading frame encoding the 20,684 polypeptide shows marked homology to the coat proteins of three other potexviruses. The putative coat protein gene was subcloned in a T7 transcription plasmid and RNAs produced by in vitro transcription were translated in the rabbit reticulocyte lysate system. The polypeptide products comigrated on SDS-polyacrylamide gels with one of those synthesized by the in vitro translation of viral RNA, and were immunoprecipitable with antiserum raised against WCIMV, confirming the location of the coat protein gene. PMID- 3341119 TI - Predominant association of adenovirus type 12 DNA with human chromosome 1 early in productive infection. AB - In human KB cells productively infected with human adenovirus type 12 (Ad12), viral DNA can recombine with cellular DNA. The functional significance of this covalent linkage is not understood. It is, however, conceivable that very early in the infection cycle integrated viral genes gain an advantage by being transcribed more effectively. In the present study, it has been shown that Ad12 DNA is associated predominantly with human chromosome number 1 and one chromosome in the CII group. This association has been detected as early as 2 hr after infection by in situ hybridization. Further work will be directed toward the analysis of viral transcription products within the first 2 hr of the infection cycle. PMID- 3341120 TI - Coconut tinangaja viroid: sequence homology with coconut cadang-cadang viroid and other potato spindle tuber viroid related RNAs. AB - The nucleotide sequence of two variants of coconut tinangaja viroid (CTiV) were obtained. Both sequence variants are 254 nucleotide residues in size but differ in sequence at two positions. In comparisons with other viroids, the sequences and proposed secondary structure of CTiV show most homology with the 246 nucleotide residue variant of coconut cadang-cadang viroid (CCCV (246]. Several regions throughout the rod-like molecules of CTiV show significant structural and sequence homology with other RNAs related to potato spindle tuber viroid. These homologies include a centrally positioned uridine bulged G:C helix and a 17 nucleotide residue sequence found in common with hop stunt viroid in the left hand end loop of both viroids. PMID- 3341121 TI - [Comparison of survival curves based on a model of proportional risks]. AB - Regression analysis of proportional risks was adapted to a two-tailed test for comparing survival of cancer patients. The method allowed both testing the hypothesis on the difference between two survival functions and evaluation of the degree of the difference. The method was applied to data on survival of patients with cancer of the cervix uteri following radiation treatment. PMID- 3341122 TI - [Diagnostic possibilities of quantitative histochemical studies of epidermoid cancer of the lung]. AB - The paper discusses the results of microspectrophotometric assay of DNA and free glycogen levels in the cells of 32 epidermoid tumors of the lung showing different degree of cell differentiation. Increased degree of tumor anaplasia was matched by a rise in DNA accumulation index and polyploidy in nuclei offset by a decrease in the glycogen level in tumor cell cytoplasm. It is suggested that DNA and free glycogen assays may contribute to the diagnostic assessment of cell differentiation involved in lung cancer. PMID- 3341123 TI - [Immediate results of the use of microsurgical technics in the treatment of cancer of the large intestine (clinical and experimental study)]. AB - The analysis of the results of 74 experiments involving large bowel resection for intestinal obstruction in rabbits demonstrated advantages offered by microsurgical procedures intended to form large bowel anastomosis. The results were used in clinical practice. The immediate results of surgery, postoperative complications and lethality were evaluated in 133 cases of large bowel cancer (anastomosis formed by microtechnique-67; by standard procedures-66). In group I, heart-lung complications resulted in one death (lethality-1.5%); group II--in 18, 13 of them being caused by anastomotic leakage and peritonitis development (lethality-27.3%). It was clinically confirmed that precision formation of large bowel anastomosis by microsurgery prevents suture failure--the main factor of postoperative lethality. PMID- 3341124 TI - [Endo-microscopic characteristics of the superficial epithelium in patients with cancer of the large intestine]. AB - In vivo studies of the large bowel mucosa in 127 patients, using colon microscopy, showed the superficial epithelium to have a heterogeneous structure comprising three major types of cellular patterns. There is a relationship between said patterns and morphological structure in the most frequent neoplasms of the large bowel. PMID- 3341125 TI - [Factors influencing the prognosis of radiation therapy of patients with uterine cancer]. AB - The results of radiation treatment of 390 cases of cancer of the corpus uteri were analysed. Five-year survival rate for the whole group was 62.1%. Such factors as stage, degree of cell differentiation, pathogenetic type of tumor, its localization within the uterus as well as patients' age and method of intracavitary irradiation appeared to influence the effectiveness of treatment. The use of spherical and chain applicators (after V. P. Tobilevich) was followed by a 7-18% increase in the efficacy of radiotherapy, as compared with linear devices. PMID- 3341126 TI - [Surgical treatment of giant cell tumors of the bones using corundo-ceramic endoprostheses]. AB - The paper discusses the data on the use of corundoceramic endoprostheses in 23 patients following excision of giant cell tumor of extremity bones. Articular ends of the long tubular bones were replaced in 20 patients and diaphysis defects in 3 cases. The 7-year experience with ceramic endoprostheses demonstrated good results in most cases. PMID- 3341128 TI - [Mucocele of the vermiform process (case report)]. PMID- 3341127 TI - [Effect of tocopherol, phenformin and thymus and pineal polypeptide factors on the transplacental carcinogenic effect of N-nitroso-N-ethylurea in rats]. AB - The study was concerned with the influence of postnatal treatment with antioxidant tocopherol, antidiabetic drug phenformin and low-molecular polypeptide factors of the thymus (thymalin) and pineal gland (epithalamin) on transplacental carcinogenicity of low-dose (7.5 mg/kg body weight, 3.2% of LD 50) N-ethyl-N-nitrosourea (ENU) in rats. Transplacental exposure to ENU was followed mainly by the development of brain tumors. Tumors of the spinal cord, peripheral nervous system and kidney were observed much more rarely. Treatment with tocopherol, thymalin or epithalamin did not significantly influence the transplacental carcinogenicity of ENU, whereas application of phenformin was followed by a decreased incidence of brain tumors. PMID- 3341130 TI - [Use of key clinical symptoms in oncology for activating the educational process]. PMID- 3341129 TI - [Teaching oncology to students and physicians]. PMID- 3341131 TI - [Integration of oncology teaching in medical institutes]. PMID- 3341132 TI - Magnetic resonance imaging for musculoskeletal disorders. PMID- 3341133 TI - Strike! PMID- 3341134 TI - Intravenous rattlesnake envenomation. AB - Intravenous envenomation by North American rattlesnakes is an uncommon occurrence, but a true emergency. In three documented, successfully resuscitated cases, the mainstay of treatment was the immediate intravenous administration of antivenin. PMID- 3341135 TI - Adrenocortical function in the acquired immunodeficiency syndrome (AIDS) AB - These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs Homer A. Boushey, Professor of Medicine, and David G. Warnock, Associate Professor of Medicine, under the direction of Dr Lloyd H. Smith, Jr, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143. PMID- 3341136 TI - Musings on whither medical education. PMID- 3341137 TI - Cystic fibrosis--on the threshold of a rational therapy. PMID- 3341138 TI - AIDS, cancer, and snakebite--what do these three have in common? PMID- 3341139 TI - The efficacy of PlA1-negative platelet transfusion therapy in posttransfusion purpura. PMID- 3341140 TI - Vitamin A intoxication presenting with ascites and a normal vitamin A level. PMID- 3341141 TI - Dysgonic fermenter-2 infections. PMID- 3341142 TI - Categorization of hospital emergency services. PMID- 3341144 TI - Record increase of syphilis in California. PMID- 3341143 TI - Prognostic factors in hypoxic-ischemic coma. PMID- 3341146 TI - Health care costs. PMID- 3341145 TI - California's male suicide rate at record high. PMID- 3341147 TI - House staff well-being. AB - From a survey of 281 house-staff members of a university medical center, we found that nearly half the respondents were afraid to complain about their training programs and were concerned that their relationship with their partner would not survive the residency. In all, 40% reported that anxiety or depression impaired their performance for a month or more; 12% reported an increased use of alcohol, marijuana, or cocaine; and 7% an increased use of sedatives, stimulants, or opioids. Stressors and dysfunctional behaviors did not differ significantly between male and female house staff, but many women had more tenuous support systems. Married house staff had stronger support systems and less substance abuse, anxiety, and depression. Departments differed widely in house-staff morale, available social supports, and the frequency of dysfunctional behaviors. Residency program directors should assess their house staff's distress and study and initiate means to reduce stress, increase support, and facilitate coping. PMID- 3341149 TI - Identification, mapping and cloning of the thymidine kinase gene of fish lymphocystis disease virus. AB - The thymidine kinase (TK) gene of fish lymphocystis disease virus (FLDV) was identified by biochemical transformation of 3T3 TK negative (TK-) to 3T3 TK positive (TK+) cells using specific viral DNA sequences. DNA fragments of the viral genome used in this study were obtained from a defined gene library of FLDV genome containing the complete viral DNA sequences. The selection of the converted cells was carried out under the condition of the HAT selection procedure. The results of these experiments revealed that the EcoRI FLDV DNA fragment C (11.2 kbp; 0.611 to 0.718 map units) is able to transform 3T3 TK- to 3T3 TK+ cells. Additional experiments using the subclones of EcoRI DNA fragment C revealed that DNA sequences of 4.1 kbp size between the coordinates 0.669 to 0.718 of the FLDV genome possessed the ability for biochemical transformation, indicating that the TK gene locus is located in this particular region. PMID- 3341148 TI - [Intermediate filament proteins as markers in tumor diagnosis]. AB - Classification of tumors is based on histogenesis and on determination of malignancy. In well differentiated neoplasias the tumor tissue reveals a similar morphological pattern similar to that of the normal tissue from which they have originated. In contrast less differentiated neoplasias do not show such similarities to normal tissue in conventional stains and special procedures such as electron microscopy or immunohistology have to be performed in order to detect cell specific products. In many undifferentiated tumors this is not possible because loss of differentiation and organisation in tumor cells do not allow the production of cell specific substances. A new possibility for determining the histogenesis of tumors is the use of antibodies which are specific for one type of intermediate filaments. Intermediate filaments are structures, which together with microtubules and microfilaments form the cytoskeleton. Intermediate filaments are composed of different polypeptides, which show a cell type specificity. Keratins are the intermediate filaments characteristically found in keratinizing and nonkeratinizing epithelia. Desmin is the specific intermediate filament type of sarcomeric, visceral and some type of vascular smooth muscle tissue. Vimentin filaments are characteristic of endothelial cells, fibroblasts, macrophages, chondrocytes and most but not all lymphatic cells and the only intermediate filament type present in these cells. Neurofilaments are composed of three different polypeptides, which form the so called neurofilament triplet and are characteristically found in central and peripheral neurons. Glial fibrillary acidic protein (GFAP) forms the intermediate filament system of normal and reactive astrocytes and also some ependymal cells contain GFAP. Thus cells and tissues can be divided into five different types by the use of appropriate polyclonal or monoclonal antibodies. In the current study we were interested to determine with a large number of specimens, whether primary tumors or metastases continue to express the intermediate type characteristic of the normal tissue. The following results demonstrate, there is abundant evidence that intermediate filaments can be used as cell type specific markers both for normal tissue and for tumors. 1. To exclude wrong negative results by intermediate filament typing, a reliable detection of intermediate filaments should be performed on cryostat sections or on material, which has been recently ethanol fixed and paraffin embedded. With many antibodies fixation of the tissue in formalin results in a decrease of reactivity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3341151 TI - Secretory otitis media--a question of surface activity in the eustachian tube? AB - An improved thin-layer chromatographic assay for monitoring phospholipid ratio in mucus was used to study the respiratory system distribution of children with and without secretory otitis media. Phosphatidylcholine, phosphatidylethanolamine and sphingomyelin abound, while only traces of other phospholipids are found. Analyses show more sphingomyelin and less phosphatidylcholine in the Eustachian tube and nose than in the lung, while phosphatidylethanolamine has about the same distribution. The phosphatidylcholine/sphingomyelin ratio is significantly less in Eustachian tube mucus from children with secretory otitis media compared with otologically healthy children, which indicates a different secretory pattern of the cells in the Eustachian tube of these children. The distribution of phospholipids in middle ear secretion is different from the distribution obtained from the Eustachian tube in children with secretory otitis media thus verifying a clearance 'blocking' of the tube caused by the disease. PMID- 3341150 TI - Tick-borne borreliosis and facial palsy. AB - During a one-year period, 82 consecutive patients seeking medical attention for facial palsy primarily of unknown etiology were examined for underlying Ixodes ricinus-borne borreliosis. Evidence of the infection was found in 16 (20%) of the patients, most of whom had cerebrospinal fluid findings indicating meningeal involvement. Among 9 children included in the study, borreliosis was found in 6 cases. Bilateral facial palsy occurred in 3 of the borrelia-infected patients, as compared with none of the patients without borreliosis. It is suggested that, in areas where the tick vector is present, borreliosis should be regularly sought in patients with facial palsy of otherwise unknown etiology. As regards the serological diagnosis, it is emphasized that normal borrelia antibody titres in serum and cerebrospinal fluid at the time of the first consultation do not exclude the infection. A careful serological follow-up of patients with facial palsy is therefore recommended in order not to miss an underlying borreliosis which, if allowed to go untreated, implies a risk of other organ involvement and a protracted course. PMID- 3341152 TI - Tissue binding kinetics of tobramycin. An experimental study in the mouse inner ear in vitro. AB - The tissue-binding capacity of tritiated tobramycin (TM) was analysed in an organ culture system in the embryonic inner ear of the mouse. A rapid and probably irreversible binding of TM occurs within 10 min, showing about 100 micrograms TM per gram protein in the vestibular half and about 75 micrograms TM per gram protein in the cochlear half of the labyrinth. A steady state is reached within 60 min. The TM uptake was then 390 micrograms TM per gram protein in the vestibular part and 270 micrograms in the cochlear part of the inner ear. A minor fraction of TM, of the same magnitude as initially bound, becomes irreversibly bound, whereas the slow accumulation which reaches the steady state level seems reversible. PMID- 3341153 TI - Tilt suppression of vestibulo-ocular reflex in patients with cerebellar lesions. AB - The effect of tilt on the time constant of post-rotatory nystagmus was determined in a group of normal subjects and patients with cerebellar lesions. The normal subjects showed a vestibular response that decayed with a time constant of 19.6 s when upright and 7.2 s after tilt prone. Patients with midline cerebellar lesions near the uvula and nodulus had time constants that were normal in the upright position but were unaffected by head tilt. Patients with cerebellar lesions due to the Arnold-Chiari malformation showed behavior that was intermediate between that of normal subjects and the patients with midline lesions. These results provide evidence that in humans, the midline cerebellum regulates a neural network in the brainstem that perseverates peripheral vestibular input. PMID- 3341155 TI - Macula flava in the vocal fold of human fetus. AB - The histological analysis of fetal vocal folds (in humans) in serial horizontal sections revealed a dense cell accumulation at the anterior and posterior ends of the vocal fold. Macula flava posterior was identified in all analysed specimens and macula flava anterior in those older than 18 weeks. Maculae flavae are composed of mesenchymal immature cells which gradually originate from cartilaginous cells of the arytenoid or mesenchymal immature cells of the anterior commissure tendon. Macula flava posterior presents the continuation of the arytenoid and there is no delineation between macula flava anterior and anterior commissure tendon. Since macula flava posterior extends its protrusion to the place of the most intensive connective tissue organization (which begins already in fetal life), it has been concluded that both maculae have an important influence to the specific organization and differentiation of connective tissue in the lamina propria of the fetal vocal fold. PMID- 3341154 TI - Surgical versus medical treatment of nasal polyps. AB - A randomized comparison of the usual surgical removal of nasal polyps versus systemic steroid treatment was performed in 53 patients. In all, continuous topical steroid treatment was given during the one year period of observation. In both groups the initial treatment resulted in a continuous increase in mean nasal expiratory peak flow as well as in the sense of smell; these two parameters showed a temporary statistically significant difference in favour of the medically treated group. In general though, the results in the two treatment groups were alike. Therefore medical treatment is recommended for routine use. Surgical removal should be reserved for those few cases in which the presence of residual or recurrent polyps justifies the inherent risks and discomfort for the patient. PMID- 3341156 TI - Comparative anatomy of human and sheep laryngeal skeleton. AB - In a macroscopical study the dimensions of the adult laryngeal skeleton of man and sheep were compared. In both species the data for male and female were evaluated separately. In contrast to pronounced differences in size between male and female human larynges, the dimensions of both sexes in sheep proved to be very similar. In respect of 7 size values, the sheep larynx falls in the range between the male and female human larynx. This applies to most values for height, the antero-posterior diameter and the inferior breadth of the thyroid cartilage. In the sheep cricoid, the height of the lamina and the inner transverse diameter correspond closely to the human counterpart. The most conspicuous differences vis a-vis the human larynx are the narrowing of the upper portion, the absent upper incisure of the thyroid and the relatively large dimensions of the arytenoid cartilages in sheep. Since in sheep the dimensions at the level of the glottis and of the subglottic space are within the range of the human larynx, the suitability of the sheep larynx as a model for experimental clinical laryngology is discussed. PMID- 3341157 TI - Effects of ligation and irradiation on the submaxillary glands in rats. AB - Rat submaxillary glands were exposed to excretory duct ligation, high-energy electron irradiation, or a combination of both. Ligation was done on the left excretory ducts, while 24 Gy irradiation was given within 8 days in three divided doses of 8 Gy. In the combined insults, the excretory ducts (one duct per rat) were first ligated, followed by 24 Gy irradiation. The effects were analysed by morphological methods. Ligation of excretory ducts caused morphological disorganization of the gland parenchyma, with resultant disappearance of secretory granules of serous cells, shrinkage of mucous cells, dilation of ducts, pronounced fibrosis and infiltration of inflammatory cells. When irradiated, some serous cells disappeared, leaving empty fibrosed spaces, while mucous cells showed no consequential radio-damage. The combined treatment of ligation of excretory ducts and irradiation caused extensive morphologic evidence of irreversible damage, i.e. no serous cells remained, disfigured and very shrunk mucous cells extremely dilated ducts, infiltration of leukocytes and fibrotic changes of the glands. PMID- 3341158 TI - The effect of stimulus predictability and age on human tracking eye movements. AB - Human tracking eye movements were recorded in healthy volunteers of varying age. The target motion was either predictable (pure sinusoids or sinusoidal frequency sweep) or unpredictable (pseudorandomized). Gain and phase values for the tracking and the smooth pursuit eye movement signal were calculated as a function of target frequency from 0.2 to 2 Hz. Max. target velocity was 20 or 40 deg/sec. In the low frequency area the smooth pursuit gain for predictable stimulation was higher than the gain elicited by the pseudorandomized stimulation. In the high frequency area, gain values did not differ significantly. For the predictable stimulation, the phase of the smooth component was always a lag, increasing with increasing frequency. At low frequencies of the pseudorandomized signal a phase lead was observed. At higher frequencies the lead turned into a lag that was greater than for the predictable stimulation. The young and old groups showed reduced smooth pursuit gain values, compared with the main group specially when the target waveform was pseudorandomized. The reduced smooth pursuit ability was mostly compensated for by an increased amount of saccades. PMID- 3341159 TI - Morphology of the endolymphatic duct and sac in the Mongolian gerbil. AB - A light microscopical study of the endolymphatic duct and sac of the Mongolian gerbil is presented. This animal model was studied because of its tendency to develop a condition of body fluid imbalance which may represent a hazard to the inner ear fluid environment. Particular stress is laid on the combination of the lack of an extraosseous endolymphatic sac and the presence of elastic tissue in the subepithelial space of the sac. These findings highlight the role of this structure for the regulation of the pressure within the inner ear. Lastly, a secretory process is proposed by which a homogeneous precipitate produced in the lumen of the sac can regulate volume and pressure changes. PMID- 3341160 TI - Motility of outer hair cells as an active, actin-mediated process. AB - The cochlea of the inner ear is no longer regarded exclusively as a passive mechanical signal analyser. Active mechanical processes are thought to influence the vibration pattern of the basilar membrane. The source of these active mechanical processes is sought in the outer hair cells (OHC). These auditory sensory cells contain actin and actin-associated structural elements. Recently, isolated OHC have been demonstrated to be capable of reversible longitudinal contractions in vitro, whose molecular mechanism could not be documented, however. Furthermore, following an increase in the intracellular Ca2+ level, isolated OHC showed longitudinal motile responses in the presence of ATP. We now report that the observed Ca2+/ATP induced mechanical events in OHC are active processes, that are driven by the hydrolytic energy of ATP. Moreover, motile responses are frequently associated with a movement of the cuticular plate, including the stereociliary bundle. Cytochalasin B, inorganic bisphosphate, trifluoperazine and antiactin inhibit the motile response. Thus, our results show that outer hair cells possess actin-dependent Ca2+ and calmodulin-controlled motor properties, so that potentially they can actively adjust the mechanical properties of the basilar membrane during auditory stimulation. PMID- 3341161 TI - Frequency selectivity: reliability of electrocochleographic measures with iso intensity masking. AB - In a group of 12 normal or hearing-impaired subjects, frequency selectivity was determined psychoacoustically and electrophysiologically with the fast ECochG iso intensity masking procedure, using a 4 kHz test tone and simultaneous pure-tone masking. Psychoacoustic curves measured twice for each subject were reproducible and showed a broadening related to hearing loss. The curves determined with ECochG repeated two or three times for each subject varied greatly for half of the subjects and their widths were not related to hearing loss. ECochG measures were reproducible in the cases where the amplitude of the response was larger. The data set out the conditions and limits of this ECochG procedure for clinical use. PMID- 3341162 TI - Effect of interaction between noise and toluene on auditory function in the rat. AB - Rats were exposed to toluene (1000 ppm, 16 h/d, 5 d/w, 2 w), or noise (100 dB Leq, 10 h/d, 7 d/w, 4 w) or toluene followed by noise. Auditory function was tested by brainstem audiometry using a 1/3 octave filtered sine wave stimulus at the frequencies 1.6, 3.15, 6.3, 12.5 and 20.0 kHz. A high-frequency auditory impairment was observed after exposure to toluene alone and noise alone. A slight recovery was recorded 1 and 6 months after the toluene exposure. Toluene followed by noise resulted in a higher threshold at all frequencies. A slight recovery was recorded 6 months post-exposure. The threshold shift exceeded the summated loss caused by toluene alone and by noise alone, particularly at 3.15 and 6.3 kHz. The latencies varied only slightly. The results indicate that the major cause of the auditory impairment was cochlear damage and that only minor injury was caused to the auditory pathways. PMID- 3341163 TI - Computer-aided three-dimensional reconstruction and morphometry of the outer hair cells of the guinea pig cochlea. AB - The outer hair cells and their nerve endings in the basal and third turns of the guinea pig cochlea were reconstructed three-dimensionally from serial thin sections by means of computer graphics, and morphometric data were obtained. The number of nerve endings in the third turn was two to three times greater than that in the basal turn. Many afferent and efferent terminals in the third turn did not demonstrate synaptic specialization. Presynaptic dense bodies were missing in the majority of outer hair cells in both basal and third turns. The morphologic arrangement of the subsurface cisternae and efferent fiber synapses on the side and base of the outer hair cells suggests a close functional relationship. The nerve fibers and cisternae may be involved in the contractile process of the cells. The volume of the outer hair cells in the first row of the basal turn was about 656 micron 3, and third turn, 1358 micron 3. The total count of mitochondria in the outer hair cells of the first row in the basal turn was 1425, and 1963 in the third turn. The density of mitochondria in the sensory cell in the basal turn was higher. The highest density was seen in the infranuclear region. The mitochondrial distribution patterns suggest that metabolic activity of the outer hair cells is higher in the basal turn than in the third turn and the energy requirement is greatest in the region close to nerve endings. PMID- 3341164 TI - Alcohol and ultrastructural changes in the developing inner ear. An in vitro study. AB - Inner ear explants from the CBA/CBA mouse were used in an organ culture system. The explants were cultured from the 16th gestational day until one day post partum. They were exposed to 1.5% or 3% ethanol in organ culture medium in order to determine any possible toxic effects upon the differentiating sensory structures of the sensory epithelium of the inner ear, that could be correlated to fetal alcohol syndrome. The higher concentration of ethanol caused a general and possibly unspecific destruction of the sensory epithelium, while the lower concentration caused characteristic changes including intracellular edema or vacuolization, especially confined to hair cells. Pathologic changes seemed dose related but not time-related. PMID- 3341165 TI - Surgical treatment of chronic middle ear disease. III. Revisions after tympanomastoid surgery. AB - Revision surgery was performed in 185 ears which had earlier undergone a total of 276 tympanomastoid operations. An open cavity had been made in 98, obliteration in 44 and canal wall up surgery in 43 ears. All ears were now operated upon by the open method combined with ear canal reconstruction and mastoid obliteration. Mastoid cholesteatoma was found in 50% of the open cavities and in 63% of intact canal wall ears, while 80% of the obliterated ears showed mastoid retraction pockets with cholesteatoma. Semicircular canal fistulae occurred in all groups, most frequently in open cavities (11%). During the follow-up period after revision (average 5 years) 3% were reoperated upon because of a new cholesteatoma. In the whole series, average hearing levels were slightly better postoperatively and in 34% of the ears the A-B gap was 20 dB at most. The main reason for failure after primary surgery was inadequate mastoid and epitympanic bone work and failure to obliterate the medial parts of the cavity thoroughly. PMID- 3341166 TI - Assessment of myocardial oxidative stress in patients after myocardial revascularization. AB - A homogeneous group of six patients, who underwent coronary artery bypass surgery, was studied to determine the presence of oxidative stress caused by oxygen-derived free radicals and its relationship with reperfusion cell damage. Biopsies were performed before ischemia and 10 minutes after reperfusion. The samples were assayed for hydroperoxide-initiated chemiluminescence and histochemical succinic dehydrogenase activity; the specimens were also studied by electron microscopy. The preischemic biopsy specimens showed chemiluminescence of 40 +/- 2 (cpm/mg protein) x 10(3), normal succinic dehydrogenase activity (grade 4), and generally preserved ultrastructure (necrotic/normal cells 5/100). However, the reperfusion biopsy specimens showed an increase in chemiluminescence to 91 +/- 19 (cpm/mg protein) x 10(3) (p less than 0.025), a partial loss of enzymatic activity (grade 2.6), and ultrastructural changes characterized by mitochondrial swelling and focal myofibrillar disorganization (necrotic/normal cells: 15/100; p less than 0.001). These observations seem to indicate the presence of oxidative stress during reoxygenation, a situation that may play a major role in the genesis of reperfusion injury. It appears to be the first observation relating free radical-induced oxidative stress to reperfusion injury in humans. PMID- 3341167 TI - Value of fluoroscopy in the detection of coronary stenosis: influence of age, sex, and number of vessels calcified on diagnostic efficacy. AB - Although fluoroscopically detected coronary artery calcification is known to correlate with the presence of coronary artery stenosis, age, sex, and extent of calcification influence the strength of this association. To clarify its diagnostic potential, we performed fluoroscopy before coronary angiography in 600 patients and analyzed the results according to all three factors simultaneously. The sensitivity of fluoroscopy for significant stenosis exceeded 65% in all groups except women less than 45 years of age. Specificity exceeded 90% in patients less than 45 years and 85% in patients less than 55 years of age, and declined significantly with age. The number of vessels calcified was an important determinant of predictive value, except in those less than 45 years of age in whom even a single mild calcification markedly increased the chance of stenosis. In patients aged 45 to 64 years, calcification of two or three vessels substantially increased the chances of stenosis, but single-vessel calcification increased the risk only slightly. In patients more than 65 years of age, fluoroscopy was not helpful in detecting stenosis, regardless of the number of vessels calcified. Our findings were similar in men and women. We conclude that if both age and the number of vessels calcified are considered, fluoroscopy can provide useful information regarding the presence of stenosis in young and middle aged patients. PMID- 3341168 TI - Paradoxical increase of ventricular fibrillation threshold in response to coronary sinus obstruction. AB - We determined the ventricular fibrillation threshold (VFT) changes in response to graded coronary sinus (CS) obstruction in 13 chloralose-anesthetized dogs with fixed heart rate (150 min-1, mean systemic arterial pressure (80 mm Hg), and cardiac index (100 ml/min.kg-1 body weight). VFT in milliamperes (VFTmA) increased linearily with CS pressure (CSP) increases up to 41.2 +/- 1.4 mm Hg (VFTmA = 6.5 + 0.14 CSP mm Hg, p less than 0.01). Total coronary venous effluent (CBF) did not change significantly, suggesting compensatory coronary vasodilation. Myocardial O2 consumption also remained unchanged. At higher CSP, both CBF and VFT declined precipitously (VFTmA = 20.9 - 0.27 CSP mm Hg, p less than 0.02). With simultaneous increases of systemic arterial along with CSP, VFT increased again along with the CSP-induced reduction of gradient until it reached 42.8 +/- 3.2 mm Hg. We conclude that with coronary venous obstruction, despite coronary perfusion gradient reduction to about 40 mm Hg, CBF remains constant. This constant flow vasodilation is associated with substantial (82%) VFT increase. The mechanism may involve enhanced homogeneity of CBF distribution and increased extracellular fluid. PMID- 3341169 TI - Electrophysiologic effects of desethylamiodarone, an active metabolite of amiodarone: comparison with amiodarone during chronic administration in rabbits. AB - During acute superfusion studies by means of the standard microelectrode technique, we previously showed that both amiodarone and its major metabolite, desethylamiodarone, had a modest effect on the lengthening of the action potential duration (APD) at high drug concentrations and produced a rate dependent block of the sodium channel in cardiac muscle. In this study the comparative electrophysiologic effects of the two compounds in rabbits treated chronically with these compounds were determined with particular reference to repolarization and sinus node automaticity. The changes were correlated with those in serum and tissue drug levels and in thyroid hormone indices. After 1 week neither compound had a significant effect on atrial or sinus nodal potentials; after 3 weeks, amiodarone increased the atrial APD at 90% repolarization time by 10.5% (p less than 0.05) and the effective refractory period (ERP) by 6.7% (p less than 0.05). The corresponding figures for desethylamiodarone were 13% (NS) and 18% (NS). The sinus cycle length was increased 12% (NS) by amiodarone and 27.9% (p less than 0.05) after the metabolite. In animals treated for 6 weeks, amiodarone increased the ventricular APD at 90% repolarization by 58.8% (p less than 0.01) and desethylamiodarone by 42.0% the corresponding figures for the ERP were 63.4% (p less than 0.01 and 47.4% (p less than 0.01), respectively. At the stimulation frequency used, neither compound exerted a significant effect on Vmax. Both amiodarone and desethylamiodarone significantly decreased serum triiodothyronine and increased reverse triiodothyronine levels but had no effect on thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341170 TI - Long-term efficacy of mexiletine alone and in combination with class Ia antiarrhythmic drugs for refractory ventricular arrhythmias. AB - The efficacy of mexiletine used alone, and in combination with a class Ia antiarrhythmic drug, was assessed in 159 previously drug-refractory patients with ventricular tachycardia (VT) during serial electrophysiologic studies and during long-term (5-year) clinical follow-up. Electrically-inducible ventricular tachycardia was suppressed by mexiletine alone in 23% of patients tested, and a combined antiarrhythmic drug regimen was effective in 29% of the trials performed. Mexiletine was much more likely to be effective in patients presenting with nonsustained VT or ventricular fibrillation than in patients with sustained VT (p less than 0.005). After 1 and 4 years of treatment, 18% and 42% of the patients treated with mexiletine alone had died suddenly or suffered recurrent symptomatic VT, compared to 11% and 25% of patients treated with the combined antiarrhythmic drug regimens (p = NS). Mexiletine therapy was associated with frequent, though readily reversible, adverse reactions. However, mexiletine treatment had to be discontinued permanently in 8 of 92 patients (9%) because of intolerable side effects. We conclude that the added efficacy and possible improved arrhythmia-free survival associated with combining mexiletine with a class Ia agent should be further investigated. PMID- 3341171 TI - Electrophysiologic effects of intravenous magnesium in patients with normal conduction systems and no clinical evidence of significant cardiac disease. AB - Parenteral magnesium has been used for several decades in the empiric treatment of various arrhythmias, but the data on its electrophysiologic effects in man are limited. We evaluated the electrophysiologic effects of magnesium sulfate (MgSO4) administration in eight normomagnesemic patients with normal mononuclear cell magnesium content, who had no clinically significant heart disease and had normal baseline electrophysiologic properties. After administration of intravenous MgSO4, serum magnesium rose significantly from 1.9 +/- 0.1 to 4.4 +/- 1.7 mg/dl (p less than 0.02). During a maintenance magnesium infusion, we observed significant prolongation of the ECG PR interval (145 +/- 18 to 155 +/- 26 msec, p less than 0.05), AH interval (77 +/- 27 to 83 +/- 26 msec, p less than 0.002), antegrade atrioventricular (AV) nodal effective refractory period (278 +/- 67 to 293 +/- 67 msec, p less than 0.05), and sinoatrial conduction time (60 +/- 34 to 76 +/- 32 msec, p less than 0.02). No significant effect was observed on sinus cycle length, sinus node recovery time, intra-atrial or intraventricular conduction times, QRS duration (during both sinus rhythm and ventricular pacing), QT interval, HV interval, paced cycle length resulting in AV nodal Wenckebach block, AV nodal functional refractory period, retrograde ventriculoatrial (VA) effective refractory period, or atrial and ventricular refractory periods. These findings, in conjunction with the demonstrated ability of magnesium to block slow channels for sodium movement, may provide an explanation of the mechanism by which magnesium exerts its effect in the treatment of atrial and junctional arrhythmias. PMID- 3341172 TI - Cardiomyopathy with arrhythmias and ectodermal dysplasia: a previously unreported association. AB - Hidrotic ectodermal dysplasia represents a group of congenital or hereditary disorders that involve ectodermal derivatives. It is characterized by partial or complete alopecia, dystrophic nails, and dental abnormalities. Dilated cardiomyopathy has not previously been reported in association with this illness. We report the cases of three children with fatal dilated cardiomyopathy with associated cardiac arrhythmias and ectodermal dysplasia. Laboratory investigations revealed no specific cause for the cardiomyopathy. It is speculated that this association is not simply coincidental. PMID- 3341173 TI - Localized septal hypertrophy: part of the spectrum of hypertrophic cardiomyopathy or an incidental echocardiographic finding? AB - In a prospective study of the results of 5582 consecutive two-dimensional echocardiographic examinations, hypertrophy of a localized region of the basal ventricular septum was identified in 26 patients. Proven diagnoses were coronary disease in five patients, coronary plus valvular disease in three, valvular disease in seven, and miscellaneous in four. Localized septal hypertrophy was the only cardiac diagnosis in seven patients. The ratio of the thickness of the hypertrophied area to that of the adjacent septum was greater than or equal to 1.7 (mean 1.93 +/- 0.19) in all patients. The ration of the length of the hypertrophied portion (mean 0.34 +/- 06) to the length (apex to base) of the septum was less than 0.39 in all but one patient. Although the mitral valve tended to be more anterior than expected in 20, other features of hypertrophic cardiomyopathy were generally lacking. Of four patients undergoing left ventricular angiography, the bulge was identified in only one in whom cranial caudal angulation was added to the 60-degree left anterior oblique view. An autopsy was performed in one patient; the hypertrophy was identified, although results of microscopic examination showed no fiber disarray. These data suggest that, in most instances, localized septal hypertrophy is an incidental echocardiographic finding. The diagnosis of hypertrophic cardiomyopathy should generally not be made on the basis of this feature alone. PMID- 3341174 TI - Pulsus paradoxus: definition and relation to the severity of cardiac tamponade. AB - Based on 101 control patients, the 95% confidence limit for the inspiratory decrease in arterial systolic pressure (delta SYST, mm Hg) and the percentage decrease in arterial systolic pressure (% delta SYST = delta SYST/expiratory systolic pressure) were determined to be 12 mm Hg and 9%, respectively. In 65 patients with pericardial effusion, the severity of cardiac tamponade was estimated on the basis of the percentage increase in cardiac output resulting from pericardiocentesis: absent = less than 20% (n = 24), mild = 20% to 49% (n = 9), and moderate or severe = greater than or equal to 50% (n = 32). The accuracy of a delta SYST greater than 12 mm Hg and % delta SYST greater than 9% in the identification of tamponade was 92% and 97%, respectively. A % delta SYST greater than 15% with relative hypotension (expiratory systolic pressure less than or equal to 120 mm Hg) or a delta SYST greater than 25 mm Hg or inspiratory pulse obliteration was found in 31 of 32 patients with moderate or severe tamponade compared to 2 of the 33 remaining patients. We conclude that the inspiratory decline in arterial systolic pressure can be used to accurately estimate the level of hemodynamic embarrassment resulting from pericardial effusion. PMID- 3341175 TI - Echocardiographic imaging of the left ventricle by peripheral intravenous injection of echo contrast agent. AB - With the use of a new echo contrast agent (ECA) that consists of a suspension with microbubbles (100% less than 3.9 micron in a moving system), we were able to opacify the left ventricle by peripheral intravenous injection in 124 of 130 patients (95%) without shunt connection. In 12 patients with aortic valve disease we measured the opacification of the right and left ventricles videodensitometrically by means of increasing doses. Dose 1 (8.7 ml ECA) and dose 4 (50 ml ECA) led to no significant difference in intensity in the right ventricle (168 +/- 32 vs 184 +/- 16 units, respectively; p greater than 0.05); however, opacification of the left ventricle was significantly more evident after dose 4 (60 +/- 60 vs 88 +/- 62 units, respectively; p less than 0.05). On the basis of the farthest distance reached by the regurgitant microbubbles from the aortic valve, the severity of regurgitation was graded on a four-point scale; the results were compared with those of aortography. A significant correlation (r = 0.98, n = 9) was found between ECA grading and aortography in the evaluation of the severity of aortic insufficiency. In addition, flow characteristics in patients with mitral stenosis, aortic insufficiency, and the regurgitation jet in incompetent aortic prosthesis in connection with diastolic inflow over the mitral valve were described. Moreover, it was possible to differentiate between inflow of ECA into the left atrium via an atrial septal defect and across the pulmonary vascular bed. No adverse effects were reported by the patients. Left ventricular end-diastolic volume index, end-systolic volume index, stroke volume index, and ejection fraction were determined before and after intravenous injection of increasing doses of ECA by means of the area-length method of Sandler and Dodge. Even after dose 4 we observed no significant changes in left ventricular function. The values before and after injection were in the range of intra- and interobserver reproducibility. Only three patients reported a slight taste sensation. In nine patients with a history of allergies there were no side effects. PMID- 3341176 TI - Early partial systolic closure of the pulmonic valve relates to severity of pulmonary hypertension. AB - Ultrasound studies in pulmonary hypertension often show systolic partial closure of the pulmonic valve and early peaking of Doppler pulmonary flow velocity, but these findings are poorly understood. Our initial observations of earlier systolic partial closure with higher pulmonary pressures suggested that this phenomenon might relate to pressure. In 30 patients with documented pulmonary hypertension, the timing of systolic partial closure and the corresponding decrease in Doppler flow velocity related inversely to pulmonary artery pressure at catheterization. Peak flow preceded the systolic velocity decrease and also related inversely to pressure. Since changing flow velocity might reflect a changing driving force across the valve, we examined simultaneous high-fidelity catheter pressure tracings from the right ventricle and pulmonary artery from 24 patients with and without pulmonary hypertension. In 30 studies, a positive right ventricular to pulmonary artery pressure gradient was present early in systole, but the gradient decreased to a minimum value in mid-to-late systole. The timing of this minimum also related inversely to pressure. We conjectured that forces opposing ejection occur earlier in pulmonary hypertension, thereby decreasing the forward driving force and allowing earlier partial systolic closure. PMID- 3341177 TI - Doppler evaluation of bioprosthetic and mechanical aortic valves: data from four models in 107 stable, ambulatory patients. AB - To test the applicability of Doppler ultrasound in the evaluation of prosthetic valve function, 107 patients with normal ejection fractions in whom Starr Edwards, Bjork-Shiley, Carpentier-Edwards, and Hancock models had been implanted in the aortic position were examined. Maximal transvalvular velocity was recorded by non-imaging continuous wave Doppler ultrasound. Means of maximal velocities by model and size ranged from less than 2 to 4 m/sec. The Starr-Edwards valve showed the highest velocities, the Bjork-Shiley the lowest, and the bioprosthetic models showed velocities in between. A significant inverse relation between velocity and size, and standard deviations averaging +/- 14% enabled the technique to measure differences between sizes of the same model. Aortic regurgitation was detected in 24% of the patients. This study, conducted in well and stable patients, established values for maximal velocity across normally functioning aortic mechanical and tissue prostheses of different models and sizes. The intersubject variability was relatively small which, together with a previously shown minimal intrasubject variability, was testimony to a methodology that should prove useful in longitudinal postoperative evaluations. PMID- 3341178 TI - Reproducibility of quantitative two-dimensional echocardiography. AB - In order to assess reproducibility of quantitative planimetry, three physicians trained in two-dimensional echocardiography performed five successive studies on one another over 2 weeks (30 total studies). Then each physician traced each study (90 total tracings) for left ventricular and atrial volumes and ejection fraction by means of a modification of Simpson's rule, and left ventricular mass and average wall thickness by means of a truncated ellipsoid formula. Calculation of intertechnician variability, intertracer variability, and 95% confidence limits showed that measurements of volumes were less reproducible than measurements of ejection fraction, average wall thickness, and mass. Mean intertracer variability of 15% exceeded mean intertechnician variability of 11%; this disparity was magnified in the subject who was technically difficult to image. Ninety-five percent confidence limits were: ejection fraction +/- 7%, average wall thickness +/- 9%, left ventricular mass +/- 12%, left ventricular end-diastolic volume +/- 11%, stroke volume +/- 14%, left ventricular end systolic volume +/- 15%, and left atrial volume +/- 19%. Reproducible planimetry data can be obtained in normal hearts with the use of a protocol for quantitative imaging and planimetry. PMID- 3341179 TI - Intermediate-term results of the endocardial surgical approach for anomalous atrioventricular bypass tracts. AB - Between October 1974 and March 1, 1985, 26 patients with 29 anomalous AV bypass tracts underwent surgical treatment at the Medical Center of UAB, with follow-up from 1 to 14 years. Eleven of the patients underwent surgical correction of major associated cardiac anomalies. One patient had His bundle ablation, and 25 patients had direct surgical division of 28 bypass tracts with the use of an endocardial approach. Successful division was achieved in 27 (96%; confidence limits 88% to 99%) of 28 bypass tracts identified pre- and intraoperatively. There were no hospital deaths, but on formal follow-up there were three late deaths, all occurring in patients with major associated cardiac pathology. Neither preexcitation nor reciprocating tachycardia recurred, and functional status was excellent among patients without associated cardiac lesions. Because of the safety and, at least on intermediate-term follow-up, apparently curative nature of this operation (particularly for patients without other major cardiac pathology), surgical treatment is recommended for patients with bypass tracts having lethal potential, those with reciprocating tachycardia unresponsive to drugs, and to symptomatic patients facing many years of medications. PMID- 3341181 TI - Evaluation of balloon aortic valvuloplasty with transesophageal echocardiography. PMID- 3341180 TI - Critical analysis of cineangiographic criteria for diagnosis of arrhythmogenic right ventricular dysplasia. AB - Biplane 30-degree RAO and 60-degree LAO RV selective cineangiography was performed in 21 patients with significant ventricular arrhythmias (ventricular tachycardia in 14, salvos in three, and complex PVCs in seven) and a high presumption of arrhythmogenic RV dysplasia (ARVD), and in a control group of 10 presumed normal individuals. Comparing the two series revealed the lack of specificity of some angiographic images usually reported as suggestive signs of ARVD, such as slow dye evacuation of RV during the levophase and deep fissuring in the anterior wall with a "pile of plates" image. Inversely, localized morphologic and contraction abnormalities in the RV free wall were more sensitive and specific signs for diagnosis of ARVD; these were localized akinetic or dyskinetic bulges sometimes giving a true image of aneurysm (90%), wide and deep fissuring of the apex or of the inferior wall (33%), and large areas of akinesia. By order of frequency, these abnormalities were found on the apex in 71%, on the inferior wall in 52%, on the anterior wall in 48%, in the subtricuspid area in 38%, and on the pulmonary infundibulum in 33%. These localized lesions can suffice for the diagnosis of RV dysplasia in the absence of associated pathologies, such as ischemic heart disease or congenital defects. Usually a global RV systolic dysfunction is associated in ARVD, as confirmed by greater RV volumes (134 +/- 26 vs 79 +/- 10 ml/m2 for RVEDV, p less than 0.001; 76 +/- 34 vs 32 +/- 6 ml/m2 for RVESV, p less than 0.001), and lower RV ejection fraction (58 +/- 18% vs 47 +/- 8%, p less than 0.001) in the ARVD group compared to controls. Nevertheless, normal RV volumes and ejection fraction can be observed in some localized forms with mono- or bisegmental lesions in which RV systolic dysfunction is absent or moderate, and extensive forms with multiple segmental lesions where RV systolic dysfunction is constant and often severe. Six out of 21 patients in the ARVD group exhibited obvious global or segmental LV dysfunction, indicating the possibility of biventricular forms, as previously reported in other publications. PMID- 3341182 TI - Problems encountered with catheter balloon valvuloplasty of bioprosthetic aortic valves. PMID- 3341183 TI - Visualization of an anomalous left main coronary artery with two-dimensional echocardiography. PMID- 3341184 TI - Anomalous origin of the right coronary artery from the left sinus of Valsalva: echocardiographic-angiographic correlations. PMID- 3341185 TI - Extracardiac causes of paradoxical motion of the left ventricular wall. PMID- 3341186 TI - Diastolic collapse of the left and right ventricles in cardiac tamponade. PMID- 3341187 TI - Pacemaker syndrome due to retrograde conduction in a DDI pacemaker. PMID- 3341188 TI - The contribution of color Doppler flow imaging to the assessment of a left ventricular thrombus. PMID- 3341189 TI - Right atrial angiosarcoma diagnosed by cardiac biopsy. PMID- 3341190 TI - Giant cell myocarditis: an autoimmune disease? PMID- 3341191 TI - Cushing's syndrome presenting as sudden death. PMID- 3341192 TI - Rheologic genesis of aortic coarctation in a canine model. PMID- 3341193 TI - Medical management of silent ischemia and myocardial infarction. PMID- 3341194 TI - Correlation of coronary arteriography after acute myocardial infarction with predischarge limited exercise test response. AB - This study of post-acute myocardial infarction (AMI) patients compared the extent and distribution of coronary narrowings and left ventricular dysfunction in 45 patients who had greater than or equal to 1 mm ST-segment depression on a predischarge low-level exercise test (positive-result group) with those found in 78 patients who had less than 1 mm ST depression (negative-result group). Cardiac catheterization was done 50 +/- 20 days (mean + standard deviation) after AMI. Patients with positive responses more often had multivessel coronary artery disease (80 vs 47%, p = 0.001) and a greater than or equal to 75% narrowing in the left anterior descending (LAD) (87 vs 62%, p = 0.003) and left circumflex (71 vs 37%, p = 0.001) arteries, as well as in the proximal LAD segment before the first septal branch (58 vs 29%, p = 0.002). Among patients with positive responses 93% had normal or hypokinetic wall motion in the vascular territory of a severely diseased coronary artery (viable but potentially ischemic myocardium) while 63% of the negative-result group had these findings (p = 0.001). No difference in ejection fraction could be identified between the 2 groups (54 +/- 15% vs 54 +/- 16%). Prior studies of AMI patients have shown that ST-segment depression on a predischarge low-level exercise test will identify patients at higher risk of subsequent cardiac death. Our observations have identified differences in cardiac angiographic findings between patients with positive and negative responses to this test that may explain this difference in outcome. PMID- 3341195 TI - Components of heart rate variability measured during healing of acute myocardial infarction. AB - A high degree of heart rate (HR) variability is found in persons with normal hearts, whereas low HR variability can be found in patients with severe coronary artery disease, congestive heart failure and diabetic neuropathy. Two weeks after acute myocardial infarction, low HR variability predicted reduced long-term survival even after adjusting for clinical risk indicators, left ventricular ejection fraction, HR and ventricular arrhythmias. The present study elucidated the causes of differences in HR and HR variability between patients with low and high HR variability. In a matched-pair study, 10 patients with low HR variability (24-hour standard deviation of N-N intervals less than 50 ms) were randomly selected. For each of these 10 patients, a control patient with high HR variability (24-hour standard deviation of N-N intervals greater than or equal to 100 ms), matched for age, left ventricular ejection fraction and rales in the coronary care unit was selected. Patients who were taking either digitalis or beta-adrenergic blocking drugs were excluded. Analysis of 24-hour electrocardiograms showed that for the low HR variability group compared with the high: (1) the daytime and nighttime average HR was faster; (2) the difference between daytime and nighttime HR was less; (3) the proportion of differences greater than 50 ms between successive N-N intervals was smaller; and (4) the number of HR "spikes" per day (increase in HR greater than or equal to 10 beats/min, lasting from 3 to 15 minutes) was less.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341196 TI - Short-term risk stratification at admission based on simple clinical data in acute myocardial infarction. AB - Simple clinical data, available in all coronary care units, were recorded in 1,013 consecutive patients with acute myocardial infarction (AMI). In order to identify the patients at highest and lowest risk of mortality during hospital stay, a prognostic index was established from a stepwise logistic discriminant analysis of 10 clinical variables obtained at admission in a consecutive series of 477 patients hospitalized in 1 of 2 coronary care units admitting new patients on alternate days and treating them similarly. This prognostic index was applied to a comparison group of 536 consecutive patients admitted to the other coronary care unit. In the experimental group, 57 of the 477 patients (12%) died during hospital stay; 60 of the 536 patients (11%) died in the comparison group. As individual variables, age, previous history of AMI, anterior site and left ventricular function on admission were associated with increased mortality. Three variables were selected from the stepwise logistic discriminant analysis of the experimental group: age; site (anterior = 1, other = 0); and grade of left ventricular function (0 to 4). Prognostic index = 5.9019 - 0.8961 function - 0.5708 location - 0.0369 age. This index was validated in the comparison group. Patients were allocated into different classes with increasing index values associated with decreasing risk. Three subgroups of patients were identified: high risk of hospital mortality (index less than or equal to 1; mortality: 51%), intermediate risk (index 1 to 3; mortality: 18%) and low risk (index greater than 3; mortality: 4%). The use of this simple prognostic index may improve clinical management and selection of patients for intervention trials. PMID- 3341197 TI - Significance of Doppler-detected mitral regurgitation in acute myocardial infarction. AB - To define the incidence of mitral regurgitation (MR) and elucidate its potential contribution to the development of severe congestive heart failure after acute myocardial infarction (AMI), Doppler echocardiograms were obtained within 48 hours of onset of AMI in 59 patients. The presence of MR was determined from the apical 4-chamber and parasternal long-axis views with pulsed Doppler. MR was detected in 23 of the 59 patients (39%) and was similarly frequent in patients with anterior (11 of 24 or 46%) and inferior AMI (12 of 34 or 35%). Patients with MR were older (71 +/- 3 vs 62 +/- 2 years, p less than 0.005), had a higher incidence of prior AMI (8 of 23 vs 4 of 36, p less than 0.05) and larger end diastolic volume indexes by radionuclide ventriculography (112 +/- 9 vs 72 +/- 4, p less than 0.005). A systolic murmur was heard in only 10 of 23 patients with MR detected by Doppler. Mortality determined 8 to 14 months after the index AMI was 48% (11 of 23) in patients with MR but only 11% (4 of 30) in those without it (p less than 0.01). Thus, this study determined that clinically silent MR frequently complicates AMI and its presence is associated with and is a potential determinant of severe congestive heart failure and mortality. PMID- 3341199 TI - Usefulness of the accelerated idioventricular rhythm as a marker for myocardial necrosis and reperfusion during thrombolytic therapy in acute myocardial infarction. AB - The value of the accelerated idioventricular rhythm (AIVR) as a marker for myocardial necrosis and/or reperfusion was prospectively studied in 87 patients admitted with persistent ischemic chest pain. All patients received streptokinase. Necrosis was diagnosed by new Q waves and an increase in plasma enzymes. Reperfusion was documented angiographically. Myocardial necrosis occurred in 72 patients and reperfusion in 70 patients, 58 of whom had myocardial necrosis. Of 27 patients with AIVR, 26 had both necrosis and reperfusion (p less than 0.001). AIVR started after a long coupling interval to the preceding sinus rhythm and was regular. Configuration depended on the reperfused infarct vessel. Reperfusion of the left anterior descending branch showed most configurations of AIVR and with the least QRS width. Reperfusion of the circumflex branch never had a left bundle branch block-like configuration. AIVR from reperfusion of the right coronary artery never had an inferior axis. AIVR occurring during persistent ischemic chest pain is a marker for both myocardial necrosis and reperfusion of the infarct vessel. AIVR starts with a long coupling interval and is regular. The QRS configuration may be useful for the noninvasive identification of the infarct vessel. PMID- 3341198 TI - Relation of left ventricular dilation during acute myocardial infarction to systolic performance, diastolic dysfunction, infarct size and location. AB - The quantification of left ventricular (LV) volumes and assessment of their relation to systolic and diastolic dysfunction, infarct size and anatomic location were performed in 54 patients with a first acute myocardial infarction (AMI). Blood pool radionuclide angiography was used to assess LV end-diastolic, end-systolic, and stroke volume indexes, ejection fraction and peak diastolic filling rate. Infarct size was estimated from plasma MB creatine kinase activity. Substantial LV dilation occurred within the initial 24 hours of AMI. The peak diastolic filling rate was low, even in those patients with a normal ejection fraction. In comparison with inferior AMI (n = 25), patients with anterior AMI (n = 29) had a larger end-diastolic volume index (105 +/- 8 vs 81 +/- 4 ml/m2, p less than 0.01) and end-systolic volume index (64 +/- 7 vs 37 +/- 4 ml/m2, p less than 0.001), but similar stroke volume index (41 +/- 3 vs 43 +/- 2 ml/m2, difference not significant). No significant relation was noted between infarct size estimated by MB creatine kinase and any volumetric index. On repeat study (day 10 after AMI), end-diastolic and end-systolic volume indexes increased further (p less than 0.05 vs day 1) but ejection fraction and peak diastolic filling rate were unchanged. It was concluded that: (1) LV dilation occurs within hours of AMI in both inferior and anterior AMI, but is more marked in the latter; (2) significant LV diastolic dysfunction is the rule, even in patients with preserved LV systolic function; and (3) LV dilation is an early compensatory mechanism that maintains normal stroke volume, even in patients with severely reduced LV function. PMID- 3341200 TI - Evolution of the responses to exercise in left ventricular aneurysms after anterior wall acute myocardial infarction. AB - The evolution of the heart rate, blood pressure and electrocardiographic responses to exercise in 20 patients (group A) who exhibited echocardiographic evidence of left ventricular (LV) aneurysms after acute myocardial infarction (AMI) were examined. The responses were compared with those seen in 19 patients without LV aneurysms who were matched for age, gender and location of infarct (group B). Patients taking beta blockers were excluded from the study. It was found that the heart rate response to exercise was accentuated in group A at the time of discharge from hospital and that it became attenuated over 9 to 12 months. The blood pressure response was significantly increased over 9 to 12 months in group B. Persistence of ST elevation during exercise, 10 to 12 weeks after AMI, was diagnostic of an LV aneurysm. One year after AMI the sensitivity of ST elevation was 90%, specificity was 95% and the negative predictive value 90%. PMID- 3341201 TI - Angiographic demonstration of a common link between unstable angina pectoris and non-Q-wave acute myocardial infarction. AB - The coronary morphology of ischemia-related arteries in unstable angina and Q wave acute myocardial infarction (AMI) has been described. An eccentric stenosis with overhanging edges or irregular borders (type II eccentric) was seen in most lesions less than 100% occluded and probably represented plaque disruption, nonocclusive thrombus or both. The coronary morphology of non-Q AMI has not been described. Thus, the angiograms of 106 consecutive patients catheterized with either unstable angina (n = 73) or non-Q AMI (n = 33) and an identifiable ischemia-related artery were prospectively analyzed. Non-Q AMI was diagnosed by prolonged chest pain and new and persistent ST-T changes or creatine phosphokinase twice the normal level. The results showed a higher incidence of total occlusion of the ischemia-related artery in non-Q AMI (21%) compared with unstable angina (8%) (p = 0.1). The coronary morphology of nonoccluded ischemia related arteries was similar with preponderance of type II eccentric lesions in both unstable angina and non-Q AMI. These lesions were found in 65% of ischemia related arteries in non-Q AMI but were uncommon (3%) in nonischemia-related arteries with significant (50% to 100%) stenoses. Therefore, the type II eccentric lesion is a sensitive and specific marker of less than 100% occluded ischemia-related arteries in both unstable angina and non-Q AMI. These similarities in coronary morphology suggest a similar pathogenesis, which, as previously suggested, may relate to plaque disruption with or without thrombus. Unstable angina and non-Q AMI appear to represent part of a continuous spectrum of acute coronary artery disease. Further, the management of patients with non-Q AMI should be similar to patients with unstable angina and possibly include anticoagulation and consideration for early catheterization. PMID- 3341202 TI - Use of exercise thallium-201 imaging for risk stratification of elderly patients with coronary artery disease. AB - Although coronary artery disease (CAD) may be asymptomatic, it is the most common cause of death in elderly patients in the U.S. This study examined the prognosis of 449 patients with a mean age of 65 years using exercise thallium-201 imaging. At a follow-up of 25 months, 45 patients underwent coronary artery revascularization, 8 died of cardiac causes and 10 had nonfatal acute myocardial infarctions (AMIs). Thus the total of patients with "hard" events was 18. The events included 12 of 276 patients with atypical or non-anginal symptoms versus 6 of 128 with typical angina (p = not significant); 7 of 51 patients (14%) with Q wave AMI versus 11 of 353 (3%) without Q-wave AMI (p less than 0.001); 1 of 183 patients (1%) with normal versus 17 of 221 (8%) with abnormal exercise thallium 201 images (p less than 0.002); 10 of 76 patients (13%) with multi vessel thallium-201 abnormality vs 8 of 328 (2%) with no or 1-vessel thallium-201 abnormality (p less than 0.001) and 10 of 96 patients (10%) with greater than or equal to 3 abnormal segments by thallium-201 imaging (total segments = 9) versus 8 of 308 patients with no or less than 3 abnormal segments (p less than 0.001). The number of segments with thallium-201 defects was 1 +/- 2 patients without and 3 +/- 2 in patients with hard events (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341203 TI - Body surface potential maps with low-level exercise in isolated left anterior descending coronary artery disease. AB - One hundred and twenty-lead body surface potential maps (BSPMs) were recorded at rest, at immediate cessation of exercise and after 1 (early) and 5 minutes (late) of recovery in 14 patients with isolated, critical, left anterior descending (LAD) coronary artery stenosis. Exercise endpoints, at an average peak rate of 98 +/- 13, were usual pain worsening in 13 LAD patients, and diagnostic ST depression in lead V5 in 1 patient. Twelve patients also had positive thallium scans. BSPMs were also recorded in 8 normal subjects who exercised to peak heart rates similar to those of the LAD subjects. Spatially, there were similar exercise changes in QRS and ST-segment integral patterns over the precordium and inferior torso in both groups. These were transient in the control group but persisted to late recovery in the LAD group, particularly for ST integral. Quantitatively, multivariate analysis revealed significant temporal differences between the 2 groups. However, the only independent BSPM variable was the sum of ST integral decrease, averaging --2,323 +/- 1,809 microV.s for normal patients between rest and immediate cessation of exercise, compared with -3,828 +/- 2,329 microV.s for the LAD patients (p less than 0.05). Late recovery minus rest difference averaged -1,264 +/- 1,080 microV.s for normal subjects and -2,575 +/- 1,844 microV.s for LAD patients (p less than 0.01). To control for the physiologic changes of exercise, the ST integral temporal differential maps of the normal subjects were subtracted from those of the LAD patients and the sum of negative intergroup differences was assumed to reflect only ischemia. Correlation of ST integral ischemia values at immediate cessation of exercise and late recovery was high (r = 0.88); however, intertechnique correlations of the BSPM variables with quantitative angiographic scores and thallium perfusion scan scores revealed generally low r values (range 0 to 0.52). These data demonstrate that ischemic repolarization changes are detectable and quantifiable by BSPM at low levels of cardiac stress in patients with 1-vessel disease when the usual electrocardiographic criteria of myocardial ischemia are frequently absent. The data further suggest that ST integral changes reflective of myocardial ischemia persist well after the exercise recovery period and that they are complementary to, rather than substitutionary for, other indirect measures of myocardial ischemia. PMID- 3341204 TI - An ischemic index from the electrocardiogram to select patients with low left ventricular ejection fraction for coronary artery bypass grafting. AB - Patients who have a decreased left ventricular (LV) ejection fraction (EF) may be denied coronary by-pass grafting (CABG) because it is assumed that improvement in function is unlikely. If the low LVEF were due to myocardial necrosis, this assumption would be valid. If the dysfunction were due to both necrosis and ischemia, however, then improvement may be possible with CABG. A method capable of identifying such patients would be useful. In this study, an "ischemic index" was determined for 37 patients based on the difference between the presurgical LVEF estimated from the standard 12-lead electrocardiogram by the Selvester QRS score (indicating the extent of dysfunction due to necrosis) and the presurgical LVEF measured from resting multigated radionuclide angiography (indicating dysfunction due to both necrosis and ischemia). It was hypothesized that a high ischemia index, that is, a large discrepancy between estimated and measured LVEF, would be associated with an improved post-surgical measured LVEF. The results showed that patients with an ischemic index of less than or equal to 0 had a mean decrease in LVEF of 8% (p = 0.02) and those with an index between 0 and 10 had no mean change. Patients with an index greater than or equal to 11, however, had a mean increase of 5% (p = 0.02), suggesting that depressed LVEF may improve following CABG among patients whose low function is due primarily to reversible ischemia as indicated by a high ischemic index. PMID- 3341205 TI - Methergin testing with angiographically normal coronary arteries. AB - To evaluate the incidence of spasm in patients with angiographically normal coronary arteries or with stenosis less than or equal to 50%, methergin testing was done consecutively in 1,200 patients (742 men and 458 women). The methergin test was performed 850 times during coronary angiography and 350 times after it. The test was globally positive in 11% (127 of 1,200 patients), positive in 7% among 921 patients presenting with atypical chest pain, 13% of 31 patients with effort angina, 54% of 54 with angina at rest, 57% of 53 with Prinzmetal's angina, 3% of 59 with acute myocardial infarction and 1% of 82 miscellaneous patients without chest pain. Another test was done in 291 patients after blockade of the cardiac autonomous nervous system with 0.04 mg/kg of atropine and 2 mg/kg of labetolol. The frequency of positive results in the methergin test increased after blockade from 8 to 19% (p less than 0.01). The increase of positive results was especially obvious among patients with atypical chest pain (from 6 to 14%). Thus, frequency of spasm in these patients with normal coronary arteries or without significative lesions was 11%. This incidence was influenced by the composition of the patient population and increased with blockade of the cardiac autonomous nervous system. PMID- 3341206 TI - Limited value of programmed electrical stimulation from multiple right ventricular pacing sites in clinically sustained ventricular fibrillation or ventricular tachycardia associated with coronary artery disease. AB - One-hundred and fifty patients with coronary artery disease and a documented history of sustained ventricular tachyarrhythmias were studied to determine if programmed electrical stimulation (PES) from a second right ventricular (RV) pacing site optimizes the induction of such sustained arrhythmias. The first PES test was performed from 2 RV pacing sites (apex and outflow tract or septum) using the apex first in each patient. All patients underwent a second PES within 6 to 24 hours of the first; both studies used up to 4 ventricular extrastimuli, in the absence of antiarrhythmic treatment. The second PES was performed from a single RV apical site using a pacing catheter retained from the first study. During the first day's study, 74 patients (49%) had sustained ventricular tachycardia induced from the RV apex. Only 11 of the remaining 76 patients (7% of the total group) were inducible exclusively from a second RV pacing location during the first day's testing. Seven of these 11 patients, as well as 15 additional patients who did not have ventricular tachycardia induced from either site on the first day's study, were inducible from the RV apex during the second drug-free study. Among patients with sustained ventricular tachyarrhythmias, limiting PES to a single RV site, with the option of performing a second study in those who are initially noninducible is more effective in inducing sustained ventricular tachyarrhythmias than is PES performed from 2 RV pacing sites. PMID- 3341207 TI - Developments, complications and limitations of catheter-mediated electrical ablation of posterior accessory atrioventricular pathways. AB - Nineteen patients with posterior accessory pathways and disabling, refractory arrhythmias, underwent catheter ablation using standard defibrillator pulses at energy settings of 150 to 400 J. Accessory pathway ablation was successful in 13 of 19 (68%). Effective catheter ablation correlated with local ventriculoatrial (VA) intervals determined from the coronary sinus catheter at the site of earliest retrograde atrial activation during orthodromic reciprocating tachycardia. In 12 of the 13 successfully ablated patients, the local VA interval was less than 80 ms. In 4 of the 6 unsuccessfully treated patients, the local VA interval was greater than or equal to 80 ms, p less than 0.01. Transient abnormalities noted with the procedure included sinus bradycardia (3 patients), atrioventricular block (5), accelerated junctional rhythm (3), ectopic atrial tachycardia (2), myocardial depression (1), "ischemic" appearing T-wave inversions (10) and hemodynamically insignificant small pericardial effusions (5) Creatine kinase-MB increased from 3 +/- 2 U/liter to 26 +/- 18 U/liter (p less than 0.001), 4 to 8 hours after ablation. In addition, electrical shorts occurring during the ablation procedure in 2 patients were identified and corrected only with oscilloscopic monitoring of voltage and current waveforms. Significant adverse sequelae were seen in 4 patients. Three patients required sternotomy for control of cardiac tamponade secondary to a ruptured coronary sinus and 1 patient had a small posterior left ventricular infarction related to spasm of a right coronary artery extension branch. Coronary sinus rupture correlated with the ratio of catheter diameter to coronary sinus diameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341208 TI - M-mode echocardiograms for determination of optimal left atrial timing in patients with dual chamber pacemakers. AB - To determine if the A wave of the mitral valve echocardiogram can be used as a marker for left atrial (LA) activity and assist in the programming of dual chamber pacemakers, 156 echocardiograms with the mitral A wave present were obtained from 23 patients with dual chamber pacemakers, all of whom had bipolar esophageal recordings of LA depolarization. Twelve of these patients also underwent hemodynamic study with cardiac function determined at 5 different pacemaker settings: ventricular demand pacing and dual chamber sequential pacing at 0 or 25, 150, 200 and 250 ms programming atrioventricular (AV) delay. The time delay from right atrial pacing artifact to onset and peak of mitral A wave was linearly related to the time from atrial pacing artifact to LA depolarization on the esophageal lead (p less than 0.001). As pacing mode changed from dual chamber sequential pacing (DVI) mode to atrial synchronous-ventricular pacing (VDD), the A wave came earlier relative to the ventricular pacing spike, linearly related to the LA to ventricular extension with mode change determined with the esophageal lead (r = 0.94, p less than 0.001). The time from atrial pacing to peak of A wave was shorter in patients whose optimal programmed AV delay was 150 ms compared with those whose optimal AV delay was 200 or 250 ms (p less than 0.02). At the optimal programmed delay for cardiac output, the peak of the A wave was an average of 13 +/- 36 ms after the ventricular pacing spike.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341209 TI - Clinical and hemodynamic comparison of VVI versus DDD pacing in patients with DDD pacemakers. AB - To identify better those subgroups of pacemaker recipients who will benefit from dual chamber pacing, 19 patients with DDD pacemakers that were physiologically paced were entered into a blinded, randomized protocol comparing long-term VVI versus DDD pacing. Patients were evaluated in each of the pacing modes for exercise performance, cardiac chamber size, cardiac output, functional status and health perception. Eight patients (42%) insisted on early crossover, from VVI to DDD pacing, after only 1.8 +/- 1.4 weeks because of symptoms consistent with pacemaker syndrome. Overall, 12 patients preferred DDD pacing and no patient preferred VVI pacing (p = 0.001). Percent fractional shortening (30 +/- 8 vs 24 +/- 6%, p = 0.009) and cardiac output (6.3 +/- 2.6 vs 4.4 +/- 2.2 liters/min, p = 0.0001) where significantly greater in the DDD mode. Exercise duration was greater during DDD compared with VVI pacing (11.3 +/- 3.7 vs 10.1 +/- 3.7 minutes, p = 0.006). However, it was only in the crossover subgroup that DDD pacing resulted in significant improvement in exercise performance and health perception compared with VVI pacing. This subgroup of patients was characterized by an intrinsic sinus rate of less than 60 beats/min (4/8 vs 0/11, p = 0.006), ventriculoatrial (VA) conduction (4/8 vs 1/11, p = 0.048), greater increase in exercise peak systolic blood pressure from VVI to DDD mode (21 +/- 12 vs 4 +/- 13 mm Hg, p = 0.02) and greater improvement in exercise capacity from VVI to DDD pacing (2.2 +/- 1.2 vs 0.6 +/- 1.4 minutes, p = 0.03) compared with the other 11 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341210 TI - Comparative quantitative electrophysiologic effects of adenosine triphosphate on the sinus node and atrioventricular node. AB - A pharmacologic approach was used to characterize the sinus node (SN) and atrioventricular (AV) node responses to intravenous adenosine triphosphate (ATP) in 21 patients during electrophysiologic testing. ATP produced dose-dependent prolongation of spontaneous sinus cycle length. The mean maximal increase in sinus cycle length was 294 +/- 60 ms (n = 10). The mean dose of ATP required to produce this maximal sinus cycle length prolongation was 3.5 +/- 1.0 mg. The dose response curve for sinus cycle length prolongation was sigmoid in shape with an EC50 of 0.39 mg derived from a median effect plot. There was a negative correlation between the control sinus cycle length and the dose of ATP required to produce the maximal prolongation of cycle length (p less than 0.05). In contrast, the mean dose of ATP producing AV block was 4.4 +/- 0.97 mg and the EC50 was 2.98 mg. There was a positive correlation between the AV nodal functional refractory period and the prolongation of the AH interval with a 2 mg dose (p less than 0.05). Consistent with the AV nodal dose-response curves, 8 mg ATP terminated paroxysmal reentrant supraventricular tachycardia at the AV node in 8 of 9 patients. Thus, SN and AV node responses to ATP have differences in their electrophysiologic correlates and EC50. These findings suggest that ATP has potentially different mechanisms of action on SN automaticity and AV nodal conduction that requires further investigation. PMID- 3341212 TI - Electrophysiologic effects of propranolol in intraventricular conduction disturbance. AB - Sixteen patients underwent electrophysiologic studies before and after intravenous infusion of propranolol, 0.1 mg/kg. All of them had intraventricular conduction disturbances. A significant (p less than 0.01) increase occurred after propranolol in the mean spontaneous cycle length (mean change 122 ms) and the AH interval (mean 28 ms). The HV interval did not change significantly. The effective refractory period of the His-Purkinje system increased in 4 of 5 patients (mean net change 44 ms, p greater than 0.10). In 7 patients with phase 3 infranodal block, the longest cycle length for producing block increased after propranolol in 5 and remained unchanged in 2 (mean increase 40 ms, p less than 0.02). Two patients showed phase 4 atrioventricular block. Propranolol increased the critical cycle length by an average of 120 ms. Propranolol-induced bradycardia restored stable atrioventricular conduction in 2 patients with intermittent 2:1 block but facilitated the occurrence of high grade infranodal block in 1 patient. Thus, propranolol can impair His-Purkinje conduction in patients with preexisting infranodal abnormalities. PMID- 3341211 TI - Usefulness of adenosine for arrhythmias in infants and children. AB - Adenosine was administered to 25 infants and children (11 patients after presenting with a sustained arrhythmia, and 14 during a diagnostic electrophysiologic study) to determine its electrophysiologic effects. Adenosine was given as an intravenous bolus (starting dose 37.5 micrograms/kg, and increased by 37.5 micrograms/kg increments until an effect was seen). Adenosine caused tachycardia termination or transient increased atrioventricular (AV) block in all 25 patients. Seven patients had tachycardia requiring only the atria for perpetuation and developed increased AV nodal block (minimum effective adenosine dose range 37.5 to 350 micrograms/kg, mean 131). Thirteen had AV reciprocating tachycardia or AV node reentry tachycardia (minimum effective adenosine dose range 37.5 to 225 micrograms/kg, mean 114). Four other patients received adenosine to rule out preexcitation (minimum effective adenosine dose range 37.5 to 375 micrograms/kg, mean 165). One of the 25 patients had junctional ectopic tachycardia and adenosine administration caused retrograde AV block. Six of the 25 (24%) had noticeable but minor side effects. One patient had sustained bradycardia (2 to 3 minutes requiring temporary pacing). Adenosine is a safe and effective agent in the evaluation and treatment of infants and children with arrhythmias. PMID- 3341213 TI - Clinical significance of exercise-induced bundle branch block. AB - To evaluate the diagnostic significance and long-term follow-up data of patients with exercise-induced bundle branch block (BBB), 10,176 consecutive patients' exercise test data were reviewed and 50 patients found to have exercise-induced BBB. Clinical, exercise test and arteriographic data were analyzed along with follow-up data during a mean of 43 months. Of the 50 patients, 37 had exercise induced left BBB and 13 had exercise-induced right BBB. Significant coronary artery disease (CAD) was diagnosed in 26 of 37 patients (70%) with exercise induced left BBB and in all 13 patients (100%) with exercise-induced right BBB. In patients who underwent coronary arteriography, data demonstrated a high prevalence of proximal left anterior descending disease (17 of 20, 85%). Follow up data revealed that exercise-induced BBB was associated with a 36% (18 of 50) incidence of coronary events, including 16 patients who underwent coronary artery bypass grafting and 2 hospitalized for congestive heart failure. Results indicated that exercise-induced BBB was infrequent and occurred primarily in association with CAD, had a high prevalence of proximal left anterior CAD, infrequently had similar onset and offset heart rates, was reproducible and associated with a greater incidence of coronary artery bypass grafting than had been previously reported, although the incidence of cardiac events was similar to those investigations. PMID- 3341214 TI - Linking by collision initiated in the absence of preexisting reentrant tachycardia. AB - Dynamic functional block in 1 limb of a reentrant circuit ("linking") can be maintained by either repetitive interference or collision of successive impulses entering the circuit. Occurrence of linking by collision during attempted overdrive pacing of reentrant tachycardias accounts for the entrainment phenomenon. To investigate whether linking by collision can be initiated in the absence of preexisting tachycardia, a human reentrant circuit model was studied. The model consisted of the atrioventricular node and His-Purkinje system as anterograde limb and an electronic stimulator that served as "retrograde limb" by initiating a paced atrial impulse at a predetermined ventriculoatrial interval following each sensed ventricular depolarization. In 3 patients with intact ventriculoatrial conduction, "reentrant tachycardia" was initiated by a ventricular extra-stimulus (V2), which retrogradely blocked bilaterally below the His bundle. When this same V2 was followed, instead, by a paced V2V2 train at a cycle length equal to the programmed ventriculoatrial interval of the "tachycardia," it could be shown that each beat of the train not only "traversed" the simulated "retrograde limb" but also retrogradely collided with a prior circulating impulse in the anterograde limb of the circuit, thereby constituting linking by collision at a supra-Hisian level with inability of even a single "reentrant cycle" to be completed; "tachycardia" became manifest only after termination of the V2V2 train. The findings suggest the existence of a unique mechanism for initiation of certain clinical reentrant tachycardias during incremental pacing. PMID- 3341215 TI - Assessment by autonomic blockade of age-related changes of the sinus node function and autonomic regulation in sick sinus syndrome. AB - Age-related changes of the sinus node (SN) function and the autonomic influence on the SN function were evaluated in 65 patients with sick sinus syndrome (range 14 to 84 years). Heart rate (HR), corrected SN recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) autonomic blockade (propranolol 0.2 mg/kg plus atropine 0.04 mg/kg intravenously). Percent of autonomic chronotropies of the SN function were calculated by the following formulas: (1)--(intrinsic HR--basic HR/intrinsic HR) X 100; (2) (intrinsic corrected SN recovery time--basic corrected SN recovery time/intrinsic corrected SN recovery time) X 100; (3) (intrinsic sinoatrial conduction time--basic sinoatrial conduction time/intrinsic sinoatrial conduction time) X 100. Basic HR, basic corrected SN recovery time and basic sinoatrial conduction time did not vary with age. Intrinsic HR decreased with age, but this correlation was weak (r = -0.54, p less than 0.001). Intrinsic corrected SN recovery time and intrinsic sinoatrial conduction time tended to increase with age (r = 0.26, p less than 0.05; r = 0.29, p less than 0.05, respectively). Percent chronotropies of HR, corrected SN recovery time and sinoatrial conduction time were negative values in younger patients and positive values in elderly patients; they correlated positively with age (r = 0.59, p less than 0.001; r = 0.60, p less than 0.001; r = 0.43, p less than 0.001, respectively). Thus, the basic SN function did not change with age, while the intrinsic SN function deteriorated with age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341216 TI - A new and simple method to measure maximal aortic valve pressure gradients by Doppler echocardiography. AB - Most echocardiographic laboratories now use continuous-wave Doppler to measure transvalvular pressure gradients in patients with valvular aortic stenosis (AS). In many cases, particularly in the elderly, this technique can be difficult and time-consuming, and there is no immediate means of verifying the accuracy of the results. In the present study, a new and simple method is proposed to calculate maximal aortic valve gradients from the pulsed-wave Doppler tracing recorded in the left ventricular outflow tract. The method consists of calculating maximal aortic flow velocity and thus the maximal gradient by extrapolating to their point of intersection the initial accelerating velocity and the terminal decelerating velocity recorded on the pulsed Doppler tracing. In 20 patients with varying degrees of AS, there was an excellent correlation (r = 0.96, p less than 0.001) between the results obtained by this method and those obtained by continuous-wave Doppler. In 10 patients who had cardiac catheterization, the results also correlated well with the maximal gradient (r = 0.93, p less than 0.001) measured at cardiac catheterization. Because the method is simple, it should become an integral part of the Doppler examination in patients with AS. Its main advantages will be to serve as an independent confirmation of the results obtained by continuous-wave Doppler and to reduce in many patients the duration of the examination. PMID- 3341217 TI - Tricuspid and mitral regurgitation detected by color flow Doppler in the acute phase of Kawasaki disease. AB - Valvular lesions in the acute phase of Kawasaki disease were studied in 19 children. The patients were intensively observed by color flow Doppler every day from the day of hospitalization up to 12 days after the onset of the disease and 2 or more times a week thereafter, for up to 28 days. Mitral regurgitation (MR) was found in 9 patients (47%) and tricuspid regurgitation (TR) in 10 (53%). MRs were of transient type and confirmed from 7.5 +/- 1.6 (mean +/- standard deviation) to 13.1 +/- 6.5 days after the onset of the disease. Both types of valvular regurgitation were mild. The direction of regurgitation was from the center of valvular coaptation toward the posterior wall of the atrium. Neither valvular prolapse nor valvular deformity was noted. In patients with MR, left ventricular ejection fraction on M-mode echocardiography was significantly lower in the acute phase than in the convalescent phase of the disease (p less than 0.05). Using gallium-67 scintigram, the positive uptake of the isotope was noted in 7 (88%) of 8 patients with MR, but not found at all in 8 patients free of MR. These results suggest that MR and TR are often transient in the acute phase of Kawasaki disease and could be attributed to myocarditis. PMID- 3341218 TI - Frequency of cardiac contusion in nonpenetrating chest injury. AB - Seventy-five patients with nonpenetrating chest injuries were evaluated with electrocardiography, cardiac enzyme determination, 2-dimensional echocardiography and radionuclide ventriculography to document the incidence of cardiac abnormalities. Although the electrocardiograms showed ST-T wave changes in 25 patients (33%), sensitivity (47%) and specificity (79%) for echocardiographic and radionuclide abnormalities were poor. Cardiac enzymes were abnormal in 10 patients (13%), sensitivity for echocardiographic or radionuclide abnormalities, or both, was 29% and specificity 90%. Wall motion abnormalities were detected in 11 patients (18%) by radionuclide studies and in 3 patients (6%) by echocardiography. A pericardial effusion was present in 5 patients (10%). Two patients (4%) died of noncardiac causes; neither had wall motion abnormalities. This study documents the favorable outcome of patients with blunt chest injuries and does not suggest that echocardiography or radionuclide studies should be performed routinely on such patients. PMID- 3341220 TI - Effect of propranolol on the left ventricular response to the Valsalva maneuver in normal subjects. AB - Ten normal subjects performed the Valsalva maneuver before and after the administration of propranolol (1 mg/kg). Changes in left ventricular (LV) size and function were assessed with noninvasive techniques (echocardiography and sphygmomanometer). Data were obtained at baseline, at 20 seconds of the strain phase (phase II) and 10 seconds after the release of strain (phase IV). In the control state (before propranolol), blood pressure decreased during phase II and exceeded baseline after the release of strain ("overshoot") in phase IV; after the administration of propranolol, the pressure overshoot characteristic of phase IV was no longer present. End-diastolic dimension decreased during the strain phase, but returned to baseline values during recovery in both control and propranolol states. LV stress-dimension and stress-shortening relations before and after propranolol indicate that an increase in LV contractility beginning during phase II and extending into phase IV was attenuated after propranolol. Although the absence of phase IV blood pressure overshoot may be clinically useful in identifying patients with impaired left ventricular function, beta adrenergic receptor blocking agents can also produce this hemodynamic response in the presence of normal ventricular function. PMID- 3341219 TI - Left ventricular filling in sickle cell anemia. AB - M-mode echocardiography was performed on 11 normal black subjects and 38 patients with sickle cell anemia while they were at rest to evaluate their left ventricular (LV) systolic and diastolic function. The patients with sickle cell anemia were also evaluated by radionuclide exercise tests and, based on their ejection fraction (EF) response, were separated into 2 groups: a group with a normal EF response to exercise (73 +/- 9%, mean +/- standard deviation) and a group with an abnormal EF response to exercise (53 +/- 9%). Computer-assisted analysis of the M-mode echocardiograms identified abnormalities of diastolic function (impaired left ventricular filling) in patients with sickle cell anemia compared with the normal subjects. The abnormal EF response group had significantly more impaired diastolic function and did less exercise than the normal EF response group. Both groups of patients had a decrease in left ventricular end-diastolic volume during exercise. The patients with sickle cell anemia had abnormalities of systolic and diastolic function on echocardiographic and radionuclide testing. The abnormalities in diastolic and systolic function assumed greater significance at the increased heart rates associated with exercise, accounting for the decrease in left ventricular end-diastolic volume and the abnormal EF response, and contributed to exercise intolerance in patients with sickle cell anemia. PMID- 3341221 TI - Prevalence and significance of gallium-67 uptake in the heart after open-heart surgery. AB - Radioactive gallium-67 (Ga-67) has been shown to accumulate within areas of pericardial inflammation. The present study estimated prospectively the prevalence and clinical significance of Ga-67 uptake in the heart in 62 patients 10 to 16 days after open-heart surgery. Of 62 patients studied, markedly diffuse Ga-67 uptake was detected in 21 (34%) and focal or mild diffuse uptake in 23 (37%). Results were negative in 18 (29%). Nine patients with a negative scan result (50%) had received corticosteroid therapy before imaging, whereas only 2 patients with a positive scan result (5%) were receiving steroids. The erythrocyte sedimentation rate and C-reactive protein level were both higher in patients with Ga-67 uptake compared with those with a negative scan result (p less than 0.01 in both). No other clinical, echocardiographic or electrocardiographic indicators of postpericardiotomy syndrome were related to Ga 67 uptake. No patient developed cardiac tamponade or constrictive pericarditis during the 12-week follow-up and the Ga-67 scan results did not predict the occlusion of coronary artery bypass grafts. Thus, pericardial inflammation manifested as Ga-67 uptake is a common finding after open-heart surgery and appears to be a benign condition. PMID- 3341222 TI - The Kingdom of Saudi Arabia, oil, money and cardiology. PMID- 3341223 TI - Current and future strategies in the treatment of hypertension. AB - Treatment of arterial hypertension is an important part of the medical care provided in industrialized countries today. Its rationale comes from large-scale intervention trials which have shown that lowering of elevated blood pressure reduces cardiovascular morbidity and mortality. Nevertheless, during the last few years it has been shown that treated hypertensive patients are still at an increased risk of cardiovascular morbidity and mortality compared with untreated normotensive subjects of the same age and sex. Possible explanations for this disappointing finding are that blood pressure has not been lowered to strictly normotensive levels; that some elements of the excess morbidity and mortality are not prevented by antihypertensive therapy, e.g., the part attributable to coronary artery disease; or that the drugs used may themselves have negative effects, e.g., on serum lipids, which may offset the positive effects of lowered blood pressure. It is desirable that antihypertensive treatment produces a reversal of hypertension-induced structural cardiovascular changes such as left ventricular hypertrophy or increased wall/lumen ratio in the precapillary blood vessels, but many of the current antihypertensive drug regimens have no effect on structural cardiovascular changes. Against this background it would appear logical to make renewed efforts to reduce blood pressure into the clearly normotensive range in an attempt to lower the excess risk demonstrable in treated hypertensive patients. It would also seem logical to use antihypertensive drugs that could also be expected to have positive effects on hypertension-induced structural cardiovascular changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341224 TI - Effects of verapamil on left ventricular diastolic filling in children with hypertrophic cardiomyopathy. AB - The effects of oral verapamil on resting left ventricular (LV) diastolic filling were examined in 10 children and adolescents with hypertrophic cardiomyopathy. Measurements of diastolic filling were made from gated technetium-99m radionuclide angiograms with postbeat rejection of data outside a 5% RR-interval window. LV time-activity curves were generated and the rapid-filling phase fit with a 3 degrees polynomial to calculate the peak filling rate and the time from end-systole to the point of peak filling. All patients had a radionuclide angiogram performed before and after 0.25 to 3 years of oral verapamil therapy. Verapamil did not change the LV ejection fraction but increased the peak filling rate (3.24 +/- 0.15 to 4.62 +/- 1.05 end-diastolic volume/s,p less than 0.01) and reduced the time to peak filling (217 +/- 57 to 168 +/- 63 ms, p less than 0.01). An increase in exercise endurance as measured by exercise treadmill test and subjective symptomatic improvement were also seen after verapamil therapy. Thus, in children with hypertrophic cardiomyopathy, symptomatic improvement and LV diastolic filling parameters improved with long-term oral verapamil. PMID- 3341225 TI - Cardiac malformations in relatives of children with truncus arteriosus or interruption of the aortic arch. AB - Familial recurrence risks for congenital cardiac malformations have been estimated at 1 to 4%, but little is known of recurrence risks for uncommon congenital cardiac malformations. This study determined the incidence of congenital cardiac malformations in relatives of patients with either truncus arteriosus (TA) or interruption of the aortic arch (IAA) seen between 1955 and 1985. Prior to this study, only 2 cases of IAA in siblings had been reported and the recurrence risk of TA had been estimated at 1.2%. In the families of 36 index cases of IAA, there were 98 siblings, 2 with congenital cardiac malformations (2.1%). All recurrences were in IAA type B families. Single cases of congenital cardiac malformations were found in second- and third-degree relatives and 2 cases in more distant relatives. In the families of 49 index cases of TA, there were 106 siblings, 7 with congenital cardiac malformations (6.6%). Two had TA, 3 had other conotruncal anomalies and 2 had other congenital cardiac malformations. Two parents had congenital cardiac malformations, 1 with TA and 1 with conotruncal malformation. Among second- and third-degree relatives, 7 had congenital cardiac malformations (5 were conotruncal, including 1 half sibling). Among greater than third-degree relatives, 3 had congenital cardiac malformations. Thus, in IAA, the recurrence rate of congenital cardiac malformations (2.1%) was higher than expected and could be related to the etiology of IAA type B as a conotruncal malformation. In TA, the recurrence rate of congenital cardiac malformations was 6.6%, higher than previously reported. When TA was complex the recurrence risk was higher (13.6%). These findings must be taken into consideration for satisfactory genetic counseling. PMID- 3341226 TI - Inducible atrial flutter after the Mustard repair of complete transposition of the great arteries. AB - Atrial flutter is a common postoperative arrhythmia in patients with complete transposition of the great arteries (d-TGA) after the Mustard repair. Sixty patients with d-TGA who had the Mustard repair were evaluated by electrophysiologic studies. Thirty-three (55%) had inducible sustained atrial flutter; 17 of them developed spontaneous clinical episodes of atrial flutter (clinical atrial flutter group) and 16 did not (nonclinical atrial flutter group). In 6 of the 17 patients (35%) with clinical inducible atrial flutter, the condition was first documented in the electrophysiologic laboratory with subsequent development of spontaneous clinical episodes. Catheter endocardial mapping, used to determine atrial activation sequences and and conduction intervals, revealed intraatrial conduction delays with late activation of the low atrial sites in all patients. Abnormalities of atrial refractoriness were present, with a greater dispersion of atrial refractoriness found in the clinical atrial flutter group. Severe abnormalities of sinus nodal function appeared to a significantly greater degree among patients who had clinical episodes of atrial flutter. These electrophysiologic abnormalities and associated arrhythmias may predispose patients with d-TGA to sudden death. PMID- 3341227 TI - Physiopathology of transient ventricular occlusion during balloon valvuloplasty for pulmonic or aortic stenosis. AB - Hemodynamic observations were made at different cardiac levels during transient balloon occlusion at the time of aortic or pulmonary valvuloplasty in 37 patients (mean age 8 +/- 9 years); 22 had pulmonary stenosis and 15 had aortic stenosis (6 valvular and 9 discrete subvalvular types). Eighty-two tentative dilatations were performed in patients with pulmonary stenosis and 61 in patients with aortic stenosis. The hemodynamics of the right and left heart were monitored during inflation-deflation time. From selected tracings mean beat-to-beat pressures curves were constructed during occlusion-recovery time. The cycle length (RR interval) did not change significantly during occlusion, except for patients with pulmonary occlusion and patent foramen ovale, where a significant increase in cycle length (p less than 0.01) was observed during recovery time. The mean maximal increase in ventricular pressure reached 95% of basal values for the right ventricle and 58% for the left ventricle. The hypertension was retrogradely transmitted to all cardiac chambers. Angiographic observations during occlusion suggest that the atrioventricular valves and the foramen ovale, when patent, become escape orifices during occlusion, for adapting and relieving intracavitary pressures. The ventricle seems to adapt to sudden occlusion by generating hypertensive and hypokinetic contractions, with atrioventricular regurgitation. PMID- 3341228 TI - Correlation of left ventricular angiographic casts and biplane left ventricular volumetry in infants and children. AB - To calculate left ventricular (LV) volumes from biplane cineangiography obtained in nonstandard views, regression equations were developed from LV casts of known volume. Volumes were calculated by the area-length method from casts ranging from 1.4 to 48.9 ml obtained from 30 postmortem cases with heart disease. The casts were divided into 2 groups: group I (n = 17) with abnormal and group II (n = 13) with normal right ventricular hemodynamics. Biplane cinegrams were taken in the anterolateral, anterior and long axial oblique, hepatoclavicular and sitting-up projections. The true volume of each cast was determined from its weight and specific gravity. In both groups, excellent correlations were obtained between measured and true volumes (r = 0.92 to 0.99) in all projections, although each projection overestimated the true volume (slope value less than 1). The regression equations obtained from group I were significantly different from those in group II in all views (p less than 0.025 to 0.05), with smaller mean differences and standard errors of the estimate. These data support the concept that right ventricular hemodynamics influence ventricular septal position and, therefore, LV geometry and measured volumes. Appropriate regression equations are required to allow volume calculation from multiple projections. PMID- 3341229 TI - Silent myocardial ischemia as a predisposing factor for ventricular fibrillation. PMID- 3341230 TI - Termination of sustained ventricular tachycardia by transesophageal atrial pacing. PMID- 3341231 TI - Pacemaker-mediated endless loop tachycardia at rates below the upper rate limit. PMID- 3341232 TI - Follow-up of the family with congenital absence of sinus rhythm. PMID- 3341233 TI - Propafenone for paroxysmal atrial fibrillation. PMID- 3341234 TI - Overestimation by Doppler echocardiography of pressure gradients across Starr Edwards prosthetic valves in the aortic position. PMID- 3341235 TI - Rupture of an aneurysmal pulmonary trunk 40 years after Blalock-Taussig anastomosis. PMID- 3341236 TI - Complex of discrete subaortic stenosis, single coronary artery arising from a small left aortic sinus, a rudimentary low-seated left aortic cusp and a congenital aortic regurgitation. PMID- 3341237 TI - Detection of thromboembolus of the right pulmonary artery by transesophageal two dimensional echocardiography. PMID- 3341239 TI - Comparison of five methods for the measurement of left ventricular ejection time. PMID- 3341240 TI - Pulmonary embolism and atrial fibrillation. PMID- 3341238 TI - Importance of adjusting left ventricular diastolic peak filling rate for heart rate. PMID- 3341241 TI - Endorphinergic pain mediation in coronary artery disease remains unclear. PMID- 3341242 TI - Maternal transmission of congenital heart disease. PMID- 3341243 TI - Pattern of congenital heart disease in children. PMID- 3341244 TI - Effects of fat intake on body composition and hepatic lipogenic enzyme activities of hamsters shortly after exercise cessation. AB - Effects of fat intake on body composition and lipogenic enzyme activities were examined in hamsters. Forty-two female hamsters were randomly divided into two groups of 21 each. One group had access to voluntary disc running; the other group was sedentary. All were fed a low-fat, high-carbohydrate diet. After 30 d, seven hamsters from each group were killed and all running activity was discontinued. Remaining hamsters were separately assigned to two groups of seven and fed either a low-fat or high-fat diet for 7 d and then killed. Voluntary running increased food intake and weight gain and reduced body fat (52%). Cessation of exercise greatly enhanced body fat gain. High-fat diet enhanced weight gain. Increased energy intake during postexercise period appeared to cause enhanced body fat gain. The high-fat diet suppressed lipogenic enzyme activities. Serum triglyceride, total cholesterol, and HDL cholesterol levels were not affected by exercise or cessation of exercise. PMID- 3341245 TI - Total-body electrical conductivity method for estimating body composition: validation by direct carcass analysis of pigs. AB - Determination of body composition by measuring total-body electrical conductivity (TOBEC) is based on the principle that body fat and fat-free mass (FFM) differ in electrical properties. In humans, we are able to estimate body composition only by indirect methods, which have been used to validate the TOBEC instrument. Relationships between TOBEC and body composition were examined using direct carcass analysis of 24 pigs differing widely in body weight and composition (48 137 kg and 14-45% fat, respectively). Highly significant correlations (p less than 0.0001) were found between body conductivity and empty-body water (H2O) (r = 0.979), empty-body FFM (r = 0.980), empty-body crude protein (r = 0.962), and empty-body potassium (r = 0.949). Prediction of empty-body H2O or FFM from TOBEC had a SEE of 2.1 or 2.8 kg, respectively. Thus, the TOBEC method can predict body H2O and FFM over a wide range of body weight and fatness. PMID- 3341246 TI - Vitamin and mineral status of trained athletes including the effects of supplementation. AB - We measured serum concentrations of thiamin, riboflavin, nicotinic acid, pyridoxine, folate, cyanocobalamin, ascorbic acid, retinol, tocopherol, zinc, magnesium, copper, iron, and ferritin as well as hemoglobin, hematocrit, percentage transferrin saturation, and total iron-binding capacity in athletes who ingested a multivitamin and mineral supplement for 3 mo. All blood variables were normal and except for pyridoxine and riboflavin there were no significant changes in the blood concentrations of any other vitamins or minerals measured. This may have been due to variable interactions between the vitamins and minerals in the supplement that prevented their being adequately absorbed. There were no signs or symptoms of serious toxic side effects. We conclude that multivitamin and mineral supplementation was without any measurable ergogenic effect and that such supplementation is unnecessary in athletes ingesting a normal diet. PMID- 3341247 TI - Vitamin and mineral supplementation: effect on the running performance of trained athletes. AB - There is limited scientific justification for the widespread use of vitamin and mineral supplements by athletes. We used a 9-mo, placebo-controlled crossover study design to determine whether a multivitamin and mineral supplement influenced the athletic performance of 30 competitive male athletes. At 0, 3, 6, and 9 mo the runners performed a progressive treadmill test to volitional exhaustion for measurement of maximal oxygen consumption, peak running speed, blood lactate turnpoint, and peak postexercise blood lactate level. Running time in a 15 km time trial was also measured. None of these variables was influenced by 3 mo of active supplementation. We conclude that 3 mo of multivitamin and mineral supplementation was without any measurable ergogenic effect. PMID- 3341248 TI - Energy expenditure and socioeconomic status in Guatemala as measured by the doubly labelled water method. AB - The energy expenditure of lower (group 1) and upper socioeconomic group females (group 2) from a marginal community in Guatemala City was determined by using the doubly labelled water method. Energy expenditure values were 1925 +/- 66 (mean, SEM) kcal/d (group 1) and 2253 +/- 145 kcal/d group 2 (p less than 0.03). About half of this difference can be attributed to size. PMID- 3341249 TI - Intestinal absorption of dietary fat from a liquid diet perfused in rats at a submaximum level. AB - The small intestine of rats was perfused in vivo for 2 h with a nutritionally complete liquid diet (68% calories from fat as corn oil). As the perfusion increased from 106 mg/2 h, the intestinal disappearance of the 14C-triolein marker remained proportional to the load up to 2,359 mg fat/2 h. Despite a decrease in absorption from 70 to 17%, this represents a very large fat intake. Fat absorption improved when medium-chain triglycerides or octanoic acid replaced corn oil (both p less than 0.01). Linoleic acid was absorbed from the diet less than corn oil (p less than 0.01). Dry ox bile reduced fat absorption (p less than 0.05); lipase and an antacid had no effect. Corn oil perfused alone was absorbed better than from the diet (p less than 0.01). Data with 14C-triolein was confirmed by dry-weight disappearance of the diet and by net intestinal water balance. Usual feeding underutilizes a large reserve for fat absorption. This reserve should be considered in therapeutic nutrition. PMID- 3341250 TI - Protein metabolism during treatment of chest infection in patients with cystic fibrosis. AB - Six cystic fibrosis patients with pulmonary exacerbations were studied to determine the effect of antibiotic treatment on protein nutritional status. Indirect calorimetry, nitrogen balance, protein turnover, urinary 3 methylhistidine, plasma albumin, prealbumin transferrin, and cortisol were measured before and after treatment. N loss averaged 16 and 17% on each balance. N in the sputum was up to 4.5% of absorbed N intake. At the peak of infection, protein synthesis, degradation, and urinary 3-methylhistidine were significantly higher than during recovery (31%, 28%, and 60%, respectively). On recovery a significant fall in blood sugar, albumin, morning cortisol and sputum N and a rise in prealbumin was found. Basal metabolic rate and N balance did not change. For patients in the fed state, active infection is associated with higher rates of protein synthesis and degradation. Antimicrobial treatment alters protein dynamics but does not alter measured N balance or the difference between measured protein synthesis and breakdown. PMID- 3341251 TI - Potassium, magnesium, and calcium balance in obese adolescents on a protein sparing modified fast. AB - Ten obese adolescents consumed the protein-sparing modified fast (PSMF), a high protein, low-carbohydrate diet, for 92 +/- 19 d and lost 14.7 +/- 5.3 kg. The effect of weight loss using the PSMF on potassium, magnesium, and calcium was evaluated using balance method at days 2-4 and 12-20, RBC-Mg, RBC-K and total body K (TBK). The vitamin- and mineral-supplemented PSMF allowed positive Ca and K balance and improved Mg balance (p less than 0.005). TBK decreased significantly, 118.7 +/- 13.7 to 97.4 +/- 1.0 g (3.04 +/- 0.35 to 2.50 +/- 0.03 mol) from baseline to 90 d (p less than 0.001), with no change in the RBC-K concentration. An unexpected finding was a significant decrease in RBC-Mg, 3.2 +/ 1.1 to 1.8 +/- 0.3 mmol/L (p less than 0.001) after 60-90 d on the diet despite maintenance of normal serum Mg level. PMID- 3341252 TI - Body fat deposition in adult obese women. I. Patterns of fat distribution. AB - Fat patterning was studied in a sample of 76 obese women before and after weight reduction by principal components analysis. Circumferences were selected as variables rather than skinfolds because circumferences correlated more highly with body composition determined either by total body water or total body potassium. A separate sample of 136 males and females, measured once, was employed to validate the results. The validation sample yielded similar findings. Two significant components were found, the first contrasting upper and lower fatness and the second trunk and extremity fatness. Waist circumference was the best predictor of upper-body fat patterning. For the lower body, thigh circumference loaded more highly than did the iliac crest circumference. Arm circumference did not contribute significantly to upper-lower fat patterning. PMID- 3341253 TI - Body fat deposition in adult obese women. II. Changes in fat distribution accompanying weight reduction. AB - This study examined changes in body fat distribution in 68 women who lost an average of 12.3 kg from an initial weight of 103.6 kg. Weight reduction was accompanied by a small but statistically significant reduction of 1.2% in the waist-to-hip ratio, suggestive of a reduction in upper-body obesity. Subjects with greater upper-body obesity tended to achieve greater reductions in the waist to-hip ratio. Changes in five circumference measures were highly correlated with losses of fat and showed that subjects with lower-body obesity tended to lose large amounts of fat from both their upper and lower fat depots while subjects with upper-body obesity lost fat primarily from their upper depots. Women with lower-body obesity tended to lose more total body fat than did women with upper body obesity (r = -0.26, p less than 0.04). PMID- 3341254 TI - Overweight as a risk factor or a predictive sign of histological liver damage in alcoholics. AB - This study analyzes whether increased body weight is related to histological liver damage in chronic alcoholic patients. Data from 152 recently abstinent alcoholics without evidences of liver failure were analyzed. Liver biopsies were scored for the presence of fat, necrosis, fibrosis, inflammation, and Mallory material. Total histological score correlated significantly with body weight (BW), length of alcoholism (L), and age (A) but not with the amount of ethanol ingested (E). Forward stepwise multiple regression analysis with histological score as the dependent variable gave significant F values for BW and L but not for A. Patients with severe damage had higher BW than patients with mild damage. The group with BW greater than 110% showed a higher histological score. These results confirm the association between increased BW and liver damage in asymptomatic alcoholic patients suggesting that overweight is a risk factor for alcoholic liver disease. PMID- 3341255 TI - Ethnic and racial differences in serum vitamin A levels of children aged 4-11 years. AB - Interpretation of differences in serum vitamin A levels observed between Hispanic and non-Hispanic children may be complicated by confounding environmental factors. Data from the Mexican-American portion of the Hispanic Health and Nutrition Examination Survey and the second National Health and Nutrition Examination Survey were used to explore these differences in 4-11-y-old Mexican Americans and non-Hispanic blacks and whites before and after accounting for vitamin-mineral supplement use and poverty status. Initial differences in mean serum vitamin A levels and prevalences less than 20 micrograms/dL (0.70 mumol/L) or less than 25 micrograms/dL (0.87 mumol/L) among the three ethnic or racial groups were reduced or eliminated after accounting for the two descriptive variables. These results support the hypothesis that differences in serum vitamin A levels between Mexican-American and non-Hispanic children in the United States are due more to environmental factors than to ethnicity. PMID- 3341256 TI - Vitamin E deficiency in phrynoderma cases from Sri Lanka. AB - Phrynoderma cases were identified in a village close to Colombo in Sri Lanka. The alpha-tocopherol level in plasma was 3.3 +/- 0.6 mumol/L among the phrynoderma patients (n = 11) and 13.0 +/- 2.3 mumol/L among the control subjects (p less than 0.002). A test on glutathione reductase activity in erythrocytes revealed a stronger riboflavin deficiency among patients than among control subjects (p less than 0.005). No significant differences were found between the groups with regard to plasma levels of retinol, retinol-binding protein, vitamin B-12, folic acid, thiamin, selenium, zinc, or essential fatty acid pattern. Primary malnutrition may partly explain the deficiency of alpha-tocopherol and riboflavin observed in phrynoderma cases. PMID- 3341257 TI - Variability of calcium absorption. AB - Variability in calcium absorption was estimated in three groups of normal subjects in whom Ca absorption was measured by standard isotopic-tracer methods at interstudy intervals ranging from 1 to 4 mo. Fifty absorption tests were performed in 22 subjects. Each was done in the morning after an overnight fast with an identical standard breakfast containing a Ca load of approximately 250 mg. Individual fractional absorption values were normalized to permit pooling of the data. The coefficient of variation (CVs) for absorption for the three groups ranged from 10.57 to 12.79% with the size of the CV increasing with interstudy duration. One other published study presenting replicate absorption values was analyzed in a similar fashion and was found to have a CV of absorption of 9.78%. From these data we estimate that when the standard double-isotope method is used to measure Ca absorption there is approximately 10% variability around any given absorption value within an individual human subject and that roughly two-thirds of this represents real biological variability in absorption. PMID- 3341258 TI - Prevention of iron deficiency by milk fortification. II. A field trial with a full-fat acidified milk. AB - In a longitudinal study from age 3 to 15 mo, 276 term, healthy, spontaneously weaned infants received a full-fat acidified milk fortified with 15 mg of elemental Fe as ferrous sulfate and 100 mg of ascorbic acid/100 g of powder and 278 control infants received milk without additives. At ages 9 and 15 mo significant differences were encountered in all measures of Fe nutriture in favor of the fortified group (p less than 0.001). Anemia (Hg less than 110 g/L) was present in 25.7% of unfortified infants compared with only 2.5% in those fortified at age 15 mo. Saturation of transferrin less than 9% was present in 33.8% and serum ferritin less than 10 micrograms/L in 39.1% of the nonfortified infants. The figures for the fortified group were 7 and 8.5% respectively. The efficiency of the fortified acidified milk in eradicating Fe deficiency in the infants while discouraging use by other family members make this milk a useful targeted product in programs of supplementary food distribution in the underdeveloped world. PMID- 3341259 TI - Inhibitory effect of nuts on iron absorption. AB - The effects on iron absorption of nuts, an important source of dietary protein in many developing countries, were measured in 137 Indian women. When the absorption from bread and nut meals (walnuts, almonds, peanuts, and hazelnuts) was compared with that from bread meals, the overall geometric mean absorption from the nut meals (1.8%) was significantly less than from the bread meals alone (6.6%, t = 9.8, p less than 0.0005). In contrast, coconut did not reduce absorption significantly. All the nuts tested contained significant amounts of two known inhibitors of Fe absorption (phytates and polyphenols) but the amounts in coconut were significantly less than in the other nuts. Fifty milligrams ascorbic acid overcame the inhibitory effects of two nuts that were tested (Brazil nuts and peanuts). This is different from that found previously for soy protein, another potent inhibitor of Fe absorption. PMID- 3341260 TI - Iron status of premenopausal women in a university community and its relationship to habitual dietary sources of protein. AB - Dietary intake and iron status was evaluated in 52 nonpregnant premenopausal women who were not using Fe supplements. Subjects were separated into three groups based on their habitual consumption of red meat (RM), fish and/or poultry (FP), or lacto-ovovegetarian (LV) sources of protein. No differences were observed among the groups in demographic characteristics (eg, age, height, weight, reported number of menstrual days per year) or total Fe intake. However, those women consuming red meat as their predominant source of protein demonstrated superior Fe status, especially reflected by higher serum ferritin concentrations (RM = 30.5 micrograms/L; FP = 15.6 micrograms/L; and LV = 19.1 micrograms/L). Thus, form rather than amount of dietary Fe appears to be most influential on Fe status; the basis for the distinctly lower Fe stores among heavy users of fish and/or poultry remains to be determined. PMID- 3341261 TI - Association of diet and other factors with adenomatous polyps of the large bowel: a prospective autopsy study. AB - The risk of developing adenomatous polyps of the large bowel was studied in 163 Hawaii Japanese autopsy subjects. They constitute a subset of 8006 men originally examined from 1965 to 1968 and of those who died from 1969 to 1984. Adenomas were found in 79 autopsied subjects but not in the remaining 84 subjects. The study looked at a number of dietary, physical, laboratory, and social variables in relation to the risk of adenomatous polyps. No significant differences were observed between subjects with and without adenomas in intake of dietary fat, proteins, or carbohydrates and in body mass index, level of physical activity, serum cholesterol, or cigarette smoking history. The only significant association was the increase in the mean number of polyps (1.04, 0.87, 1.61, and 2.34) with increasing levels of alcohol intake but the trend was not monotonic. The accrual of more subjects into the study is needed to investigate this association more thoroughly. PMID- 3341262 TI - 1987 ASCN public policy forum--Federal monitoring of the nation's nutritional status. PMID- 3341263 TI - Federal monitoring of the nation's nutritional status. Contributions of the National Center for Health Statistics. AB - The National Center for Health Statistics conducts a broad program of record based systems and population surveys providing information on the health and nutritional status of the US population. The record-based systems include vital statistics and health-care surveys. Population surveys include the National Health and Nutrition Examination Survey (NHANES), the National Health Interview Survey, the National Survey of Family Growth, and epidemiologic follow-back surveys. Although all of these data systems provide nutrition-related information, the NHANES collects the most directly relevant nutritional status data through interview and examination of a national probability sample of children and adults. The third NHANES is scheduled to begin in September 1988 and is designed to provide cross-sectional estimates of dietary intake and nutritional status for nutrition-monitoring purposes and to serve as the baseline for longitudinal studies of diet and health. PMID- 3341264 TI - Federal monitoring of the nation's nutritional status. Contributions of the US Department of Agriculture. PMID- 3341265 TI - Plasma zinc uptake and taste acuity. PMID- 3341266 TI - Serum cholesterol, lipoproteins, and plasma coagulation factors. PMID- 3341267 TI - Plasma ascorbic acid in adult males. PMID- 3341268 TI - Relationship between measles, malnutrition, and blindness. PMID- 3341269 TI - Plasma fat-soluble vitamins and alcohol consumption. PMID- 3341270 TI - Malignant mixed mesodermal tumors of the ovary. A report of 13 cases. AB - The surgical pathology files at Thomas Jefferson University Hospital (TJUH) were reviewed for the period 1973-1984. Thirteen cases of primary ovarian malignant mixed mesodermal tumor (MMT) were found; however, material from only seven of these cases could be obtained for repeat review. No conclusions can be drawn regarding any impact on survival based on the histology. Treatment was highly varied reflecting the mix of physicians rendering treatment and the range of modalities used. Overall, survival was miserable. Six of the 13 patients (46.2%) survived 6 months or less, 10 of the 13 (76.9%) survived 12 months or less. No particular treatment modality seemed to offer enhanced survival unless aggressive cytoreductive surgery was performed. A plea is made for national cooperative groups to develop treatment protocols for this aggressive ovarian cancer. PMID- 3341271 TI - Moving-strip abdomino-pelvic radiotherapy after cis-platinum-based chemotherapy and second-look operation. A feasibility study in advanced ovarian cancer. AB - Sixteen FIGO stage IIB-IV ovarian carcinoma patients who completed six to 12 courses of a cisplatinum-based combination chemotherapy and with minimal (less than 2 cm), microscopic, or no residual disease at second-look laparatomy received moving-strip abdomino-pelvic radiotherapy. Radiation treatment was feasible with acceptable toxicity; two patients had to interrupt therapy--one pretreated with 12 PAC courses because of WHO grade III leukopenia and the other because of grade III diarrhea. A third patient required surgery because of intestinal obstruction 1 month after cessation of radiotherapy. In patients with minimal residual disease at second look, the therapeutic value of sequential radiotherapy was unsatisfactory (five of six progressed), while further investigations were warranted in patients with no or microscopic residuum after second-look operation. PMID- 3341272 TI - Radical hysterectomy and pelvic lymphadenectomy versus radiation therapy for small (less than or equal to 3 cm) stage IB cervical carcinoma. AB - One hundred and three women with FIGO stage IB cervical carcinoma were treated either by radical hysterectomy and bilateral pelvic lymphadenectomy, or external pelvic radiation and intracavitary brachytherapy to deliver greater than or equal to 6000 rads to point A. Surgical therapy was to be limited to stage IB tumors measuring less than or equal to 3 cm in greatest diameter, Patients with lesions greater than 3 cm, medical contraindications to surgery, or advanced age were to be treated by radiation therapy. Of the 55 women treated surgically, 3 (5.6%) were found on final histologic evaluation to have tumors greater than 3 cm. The 5 year estimated disease-free interval was 92.3% for patients treated by surgery and 91.1% for patients treated by radiation therapy. Similar rates were achieved for the 5-year disease-free interval for lesions greater than 1 cm, 1-3 cm, and less than 3 cm in diameter by either surgery or radiation. It is tentatively concluded that radical hysterectomy and pelvic lymphadenectomy or radiation therapy as outlined above provide equally good disease-free intervals for stage IB cervical tumors measuring less than or equal to 3 cm in diameter. Because of a bias against patients treated with radiation, it is possible that radiation could lead to better results than surgery in comparable (younger, healthier, thinner) population. The advantage of surgical treatment in the younger patient is preservation of ovarian function. PMID- 3341273 TI - A randomized prospective trial using postoperative adjuvant chemotherapy (adriamycin) in high-grade extremity soft-tissue sarcoma. AB - From March 1981 to December 1984 119 patients with primary grade III extremity soft-tissue sarcoma were randomized postoperatively to single agent Adriamycin (57) or to control, no adjuvant chemotherapy (62). Adjuvant therapy was begun within 6 weeks of surgery, and consisted of Adriamycin 90 mg/m2 given over 2 days, once a month for 5 months. All patients had received preoperative intraarterial Adriamycin, radiation therapy (1,750 cGy) and subsequent surgical excision. At a median follow-up of 28 months there was no difference between the two groups in overall survival (Adriamycin = 84%, control = 80%), local tumor recurrence, or in the disease-free survival (Adriamycin = 58%, control = 54%). This study indicates that the use of single-agent Adriamycin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high grade extremity soft-tissue sarcoma treated with preoperative Adriamycin, radiation, and surgical excision. Although the Adriamycin postoperative adjuvant chemotherapy did not significantly benefit the experimental group relative to the control group, both groups of patients had an improved disease-free and overall survival rate compared to historical controls. PMID- 3341274 TI - Malignant submandibular gland tumors. A review of 91 patients. AB - A retrospective review of 91 patients with submandibular gland carcinoma seen between 1958 and 1984, is reported. Among these were 37 (41%) adenoidcystic carcinomas, 14 (15%) adenocarcinomas, 14 (15%) mucoepidermoid carcinomas, and 10 (11%) malignant mixed tumors. The median patient age was 58 (26-93) [corrected] years and the male to female ratio was was 1.2:1. At diagnosis, 15 (16.5%) patients had regional metastases and six (7%) had distant metastases. The first planned treatment was surgery in 30 (33%) patients, radiotherapy in five (5%), and surgery and radiotherapy combined in 54 (59%) patients. The 5- and 10-year cause-specific survival rates were 60 and 48%, respectively, and the relapse-free rates 42 and 34%. The locoregional control at 5 years was 30% when surgery was the only treatment, and 69% when combined with radiation. These results suggest the advantages of combining surgery and radiotherapy as the first planned treatment for most tumors. PMID- 3341275 TI - The importance of genetics for the optimization of radiation therapy. A hypothesis. AB - There is growing evidence that a fraction of cancer patients, perhaps as high as 15%, is radiation sensitive because of the action of specific genes. It seems likely that in the near future we shall be able to identify these patients by DNA probes. Therefore, we have calculated the impact on radiation therapy of removing these patients and treating the rest more aggressively. In particular, we assumed that the radiation oncologist will treat with an effective therapeutic dose corresponding to a 5% risk of serious normal tissue injury. Our results, in several instances, show a considerable increase in local control when the 5, 10, or 15% of the most radiosensitive patients are removed from the treated group. This is so, even if we assume that the tumor cells, as well as the normal cells, in radiosensitive patients are more radiosensitive than the tumor cells in patients of normal radiosensitivity. PMID- 3341276 TI - Pseudoparasitic Liesegang structures in perirenal hemorrhagic cysts. AB - Periodic structures with equally spaced radial striations identified as Liesegang like rings were seen in two male patients' hemorrhagic perirenal cysts. The patients, one 48 and the other 60 years old, had acute right-flank pain and anemia; both had nephrectomy. The rings, initially believed to represent parasites (Dioctophyma renale), were from 8 to 500 micron in diameter and had uniform, pink-tan, radially striated double walls. Multiple small rings within a larger ring predominated in one case. Morphologically, the rings differed from D. renale when compared with specimens from animals infected naturally or experimentally with the giant kidney worm. Histochemical and immunoperoxidase tests for iron, calcium, mucopolysaccharides, amyloid, keratin, and hemoglobin had negative results. Energy-dispersive x-ray elemental analysis demonstrated no detectable elements; ultrastructurally, however, the rings displayed a fine fibrillary composition with a concentric and radial pattern. These rings are believed to be an end product of a phenomenon resembling or are, in fact, the Liesegang phenomenon. Because these Liesegang-like structures may be mistaken for parasites on fine-needle aspiration or surgical specimens of hemorrhagic areas, pathologists should be aware of them. PMID- 3341277 TI - DNA aneuploidy in anaplastic carcinoma of the thyroid gland. AB - Nuclear DNA content of 19 cases of large cell or spindle cell anaplastic carcinomas of the thyroid was studied by flow cytometry. In 17 cases archival paraffin-embedded tissue and in 2 cases fresh material obtained by fine-needle aspiration biopsy was used for DNA content determination. Unequivocal evidence of DNA aneuploidy was obtained in 13 cases (68%). Two tumors contained more than one aneuploid stemline of cells. Eighteen (95%) of the patients died within 20 months after diagnosis, but 1 patient has survived for 13 years. The observed survival rate of the patients with carcinoma with a DNA index (DI) less than 1.30 was superior as compared with tumors with a DI greater than 1.30 (P = 0.007). All 7 patients with tumors with DIs greater than 1.30 died within seven months, whereas 5 of the 11 patients with tumors with DIs less than 1.30 survived longer than one year after the diagnosis. PMID- 3341278 TI - Immunologic marker analysis of normal and malignant histiocytes. A comparative study of monoclonal antibodies for diagnostic purposes. AB - The authors investigated the phenotype of "monocyte-derived histiocytes/macrophages" on frozen sections of various human tissues, in 12 histiocytic tumors, and in 15 large cell non-Hodgkin's lymphomas. The monoclonal antibodies (MAbs) considered specifically directed against antigens associated with monocytes/histiocytes included the following: Leu-M1, Leu-M3, Leu-M5, My4, My7, My8, My9, anti-Monocyte 1, anti-Monocyte 2, RFD-7, RFD-9, OKM1, and FMC17. The histiocytes in normal tissues and the tumor cells of the histiocytic malignancies expressed these antigens in various degrees. They were not reactive with MAbs specific for lymphocytes, myeloid cells, or Reed-Sternberg cells (Ki-1 antigen). Out of these 13 MAbs, only the labeling by MAb Leu-M3, Leu-M5, anti Monocyte 1, and RFD-7 was restricted to normal and malignant monocytes/histiocytes. In combination with their broad labeling of different types of monocytes/macrophages, these MAbs are of value in differential diagnostic purposes to distinguish histiocytic malignancies from large cell lymphomas. However, none of the 13 MAbs can be considered as pan-histiocytic reagents because they did not recognize all cell types belonging to the mononuclear/phagocytic system. PMID- 3341279 TI - An optimized quality control procedure for hematology analyzers with the use of retained patient specimens. AB - The authors propose guidelines for the use of retained patient specimens for the quality control of multichannel hematology analyzers. They demonstrate that control limits for patient specimen replicates may be derived from the long-term standard deviations (s) of commercial whole blood controls. They then use computer stimulation of the Coulter multichannel hematology instrument to determine power functions of various procedures using retained specimens. These power functions show that the use of three patient specimens and +/- 2 s limits are optimal for the detection of systematic error. They recommend that three different, previously analyzed normal range specimens be periodically analyzed, e.g., at eight-hour intervals. The differences between the current and original measurements should then be calculated and compared with their +/- 2 s limits. If at least two of the three differences for any directly measured parameter exceed the +/- 2 s limits, there will be a high probability of significant analytic error. Because the power functions of the derived red blood cell parameters, hematocrit, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration demonstrate relatively low error detection capabilities, the authors recommend that these parameters not be monitored with the retained patient specimen procedure. PMID- 3341280 TI - A rapid assay for platelet thromboxane production and its use in assessing prior aspirin ingestion. AB - In the laboratory evaluation of platelet disorders, there are a number of situations in which determining the capacity of platelets to synthesize thromboxane is of diagnostic value. An assay for thromboxane production is required for the diagnosis of cyclooxygenase and thromboxane synthetase defects and is useful in detecting prior aspirin ingestion. The authors describe an assay for platelet thromboxane production that is simple, rapid, inexpensive, and suitable for routine use in the clinical coagulation laboratory. It is based on platelet synthesis of 14C-thromboxane from 14C-arachidonate. 14C-thromboxane is isolated by thin-layer chromatography and its radioactivity quantitated by scintillation counting. The results are expressed as the thromboxane index: 14C arachidonate converted to thromboxane/platelet count. The assay is linear with respect to platelet concentration and substrate concentration and is independent of recovery. Using this assay, the authors demonstrated that platelet thromboxane production, expressed as thromboxane index (mean +/- standard deviation) was completely inhibited 12-16 hours after ingestion of a single aspirin dose of 650 mg (0.27 +/- 0.14), 325 mg (0.29 +/- 0.18), or 163 mg (0.13 +/- 0.13), with partial inhibition by 81 mg (0.41 +/- 0.46) or 41 mg (1.41 +/- 0.75) (n = 3 for each dose). Thromboxane index for normal controls was 2.41 +/- 0.77 (n = 25). The authors also determined the time for recovery of thromboxane synthetic capacity to normal levels in four subjects followed longitudinally after ingesting a single 650-mg dose of aspirin. Platelets from three of the four subjects recovered normal thromboxane synthetic capacity by the fifth day after aspirin ingestion, consistent with platelet half-life in the circulation. Thus, the authors have developed a rapid, inexpensive assay for assessing the function of cyclooxygenase and thromboxane synthetase in platelets, which can be especially useful as a screening test to detect ingestion of aspirin before performance of expensive and labor-intensive platelet function studies. PMID- 3341281 TI - Hemolysis in sickle cell disease as measured by endogenous carbon monoxide production. A preliminary report. AB - To detect and quantitate temporal variations of the hemolytic rate in sickle cell disease, the authors measured endogenous carbon monoxide (CO) production in five normal subjects, nine patients with sickle cell anemia (SS) in steady clinical state, and two patients with sickle cell-hemoglobin C (SC) disease in and out of pain crises. The red blood cell life span calculated from these data (RCLSco) ranged from 81.2 to 102.9 days (mean +/- standard deviation [SD] 88.0 +/- 9.2, coefficient of variation [CV] 10.2%) for the normal subjects and 8.0-24.7 days (mean +/- SD 12.1 +/- 5.1, CV 42.1%) for those with SS. Although the individual figures for RCLSco for the normal subjects and those with SS fell within the range previously obtained by radioisotopic techniques for the respective groups, the mean values calculated from the CO technique were slightly (though not significantly) shorter for the normal subjects and about 25% shorter for the subjects with SS (P less than 0.01). Repetitive studies were performed in four subjects with SS who were clinically stable; the temporal variability in the calculated hemolytic rate differed considerably from patient to patient (CV 3.6%, 7.0%, 17.0%, 28.0%). In two patients concurrent RCLS studies were performed by the CO technique and 51Cr tagged red blood cells. In one patient, the RCLS was similar by the two techniques, in the other, a two exponent 51Cr curve did not permit calculation of RCLS. In the two patients with SC disease there was no difference in RCLSco during and after recovery from pain crisis. Although the CO technique may overestimate the turnover of circulating heme mass, especially in the presence of hemolysis, the results of serial studies in a small number of patients with SS suggest but do not prove temporal variations in hemolytic rate in SS. PMID- 3341283 TI - Markers of viral replication in patients with chronic hepatitis B virus infection. AB - Serum samples from 56 patients with biopsy-proven chronic B viral hepatitis without superimposed delta hepatitis were analyzed for the various markers of viral replication, including serum hepatitis B e Ag (HBeAg), hepatitis B virus deoxyribonucleic acid (HBV-DNA), and hepatitis B core antigen (HBcAg) in the liver tissues. Twenty-seven patients had persistent viral hepatitis (PH) and 29 patients had chronic active hepatitis (CAH) with or without cirrhosis. HBV-DNA was identified in the sera of 81% of patients with PH and 60% of patients with CAH. Significantly higher levels of HBV-DNA were found in patients with PH than in those with CAH. Both HBeAg in serum and HBcAg in liver correlated positively with serum HBV-DNA. Nine patients had serum HBV-DNA in the absence of HBeAg (four had anti-HBe), and seven of these nine patients had stainable HBcAg in the liver (two did not have staining). None of these patients had hepatic HBcAg in the absence of serum HBV-DNA. When these patients were stratified according to their epidemiologic background, serum HBV-DNA was present in a significantly higher number of male homosexuals than in any other groups. This was unrelated to their status of human immunodeficiency viral serology. PMID- 3341282 TI - Evaluation of a latex agglutination test for diagnosis of Clostridium difficile associated colitis. AB - Current methods for diagnosis of Clostridium difficile-associated colitis (CAC) based on detection of cytotoxin B by a tissue culture assay (TCA) require technical expertise and up to 48 hours incubation. Recently, a latex agglutination (LA) test (Marion Laboratories) for rapid diagnosis of CAC has become available. Although early evaluations have been favorable, new evidence suggests that the LA reagent binds a soluble bacterial antigen that is not unique to toxigenic strains of C. difficile. The authors examined 201 stools received for CAC testing by LA and a reference TCA and investigated discrepant results. They obtained 29 LA(+)/TCA(+) and 155 LA(-)/TCA(-) results. Eleven patients had LA(+)/TCA(+) and 155 LA(-)/TCA(-) results. Eleven patients had LA(+)/TCA(-) results and 6 had LA(-)/TCA(+) results. The sensitivity and specificity of the LA were 83% and 93%, respectively, compared with TCA. The predictive values of positive and negative results obtained with the LA were 72% and 96%, respectively. Concentrated broth supernatants and live suspensions of three C. difficile isolates with LA(+)/TCA(-) results were tested in a rabbit ileal loop assay. All failed to demonstrate ability to produce an enterotoxin. The authors conclude that the LA method is suitable for rapid screening, but LA(+) results require confirmation by testing with other methods. PMID- 3341284 TI - Efficacy of using total bilirubin values as a guide for screening direct bilirubin requests. AB - Two divergent laboratory approaches to the determination of direct bilirubin were assessed. The first approach, assaying direct bilirubin (DB) on all total bilirubin (TB) requests regardless of TB values, resulted in a true negative rate (normal TB level less than 1.0 mg/dL [less than 17 mumol/L], and DB level, less than 0.4 mg/dL [less than 6.8 mumol/L]) of 98.7% (984/997 specimens) and a low false negative (normal TB level, abnormal DB level) rate of 1.3% (13 of 997). The second approach, assaying DB on physician request and only if the TB level was greater than or equal to 1.0 mg/dL (1.7 mumol/L), resulted in a true negative rate (normal TB level, no liver disease) of 87.7% (150%) of 171 patients) and a relatively low false negative rate (normal TB level, liver disease) of 12.3% (21 of 171) patients. Medical chart review revealed that, with either approach, none of the patients with false negative results with hepatobiliary disease would have been missed clinically, even if the DB assay had not been done. It is possible to screen DB requests using a TB of 1.0 mg/dL (17 mumol/L) as a means to determine whether DB should be assayed. PMID- 3341285 TI - Central nervous system involvement in a patient with chronic lymphocytic leukemia and non-Hodgkin's lymphoma (Richter's syndrome), with concordant cell surface immunoglobulin isotypic and immunophenotypic markers. AB - Central nervous system (CNS) involvement in Richter's syndrome has not been previously described. This report describes a 45-year-old man with the simultaneous occurrence of B-cell chronic lymphocytic leukemia (CLL), extramedullary large cell non-Hodgkin's lymphoma (NHL), and malignant lymphoid meningeal involvement. In this case, peripheral blood lymphocytes, cerebrospinal fluid (CSF) lymphoblasts, and malignant cells in surgical biopsy tissue obtained from a soft tissue mass all stained concordantly for immunoglobulin isotypes and for B-cell immunophenotypic markers, supporting the hypothesis of a clonal origin for the three malignant cell populations. These observations suggest that the different tumors in Richter's syndrome (CLL and NHL) may represent the clonal progression of a common neoplasm rather than independent neoplastic events. Richter's syndrome and other transformations of lymphoid malignancies (prolymphocytic transformation of CLL, blast crisis of CLL, and blastic transformation of NHL) may all represent possible routes of progression in the natural history of a single neoplasm. The present case also suggests that, in patients with B-cell CLL with CNS symptoms, the possibility of blastic transformation presenting as CNS lymphoma deserves consideration. PMID- 3341286 TI - White blood cell aplasia associated with thymoma. AB - A limited number of cases of acquired hypoplastic neutropenia or pure white blood cell aplasia (PWCA) associated with thymoma have been reported, in contrast to the well-documented association of pure red blood cell aplasia and thymoma. The mechanism of the aplasia in these disorders is unclear. The authors report a case of PWCA (with total absence of all granulopoietic elements in the bone marrow) in a patient with metastatic spindle cell thymoma, in which suppression of autologous granulocyte-macrophage colony-forming units by the patient's serum could be demonstrated. This finding suggests a humoral autoimmune mechanism for the pathogenesis of PWCA in this patient and lends support to the possibility that all hematologic phenomena associated with thymoma may have an autoimmune basis. PMID- 3341287 TI - Columnar-cell carcinoma. Another variant of poorly differentiated carcinoma of the thyroid. AB - An unusual case of poorly differentiated carcinoma of the thyroid is reported. The tumor occurred in a 60-year-old man, who died with widespread metastases 5.5 years after primary treatment. The unencapsulated tumor measured 8 X 5 X 9.5 cm and was composed of columnar cells. Two to three mitotic figures per 10 high power fields were present. The cells were thyroglobulin positive and not stained for calcitonin and carcinoembryonic antigen (CEA). The light microscopic appearance was similar to that of a metastasis from a carcinoma of the bowel. The authors conclude that columnar cell carcinoma is a separate type of thyroid carcinoma that shares the clinical properties of both follicular and papillary carcinoma and carries a poor prognosis. However, for practical purposes, the authors think that the tumor should be included in the category of poorly differentiated thyroid carcinomas together with the so-called insular carcinomas, mucoepidermoid carcinomas, and mucinous carcinomas. PMID- 3341288 TI - Make aggregometry more accurate. PMID- 3341290 TI - Patient samples as controls. PMID- 3341289 TI - More on leukemic hybrid leukocytes. PMID- 3341291 TI - HIV-related dysmorphogenesis. PMID- 3341292 TI - HIV embryopathy and neurocristopathies. PMID- 3341293 TI - Breast milk opioids and neonatal apnea. PMID- 3341295 TI - Ethical issues in hepatitis B screening. PMID- 3341296 TI - Growth velocity data and hypophosphatemic rickets. PMID- 3341294 TI - Sudden infant death syndrome and opioid peptides from milk. PMID- 3341298 TI - Achalasia in children. PMID- 3341297 TI - Vitamin K prophylaxis: oral or parenteral? PMID- 3341300 TI - Why pediatricians should join the AMA. PMID- 3341299 TI - Body surface cultures in the newborn infant. An exercise in futility, wastefulness, and inappropriate practice. PMID- 3341301 TI - Validity of arterial hematocrits in newborns. AB - Various methods are used to obtain specimens for hematocrit determination in neonates. We evaluated arterial sampling and found this method to be acceptable. Arterial values correlated closely with simultaneously obtained venous samples. Venous blood obtained with a tourniquet had a significantly higher hematocrit than that obtained without a tourniquet. PMID- 3341303 TI - Pediatric code cards. PMID- 3341302 TI - Pyloric stenosis in the sick premature infant. Clinical and radiological findings. AB - The clinical and radiographic features of five sick premature infants with idiopathic hypertrophic pyloric stenosis are presented. Clinical features were nonspecific, the common findings being recurrent nonbilious emesis, persistent abdominal distention, and the inability to place a nasojejunal feeding tube through the pylorus. Plain abdominal radiographs demonstrated persistent gastric dilatation in four of the infants. Idiopathic hypertrophic pyloric stenosis should be considered in the differential diagnosis of premature infants with upper gastrointestinal tract symptoms. PMID- 3341304 TI - Issues concerning AIDS embryopathy. PMID- 3341305 TI - Radiological case of the month. Menetrier's disease. PMID- 3341306 TI - Effects of testosterone therapy for pubertal delay. AB - We reviewed the effects of a brief course of testosterone enanthate (four intramuscular injections of 200 mg at three-week intervals) on pubertal advancement and final adult height in 50 male patients with delayed puberty. Although those treated with testosterone were slightly older than a group of 38 untreated subjects, the two groups had similar baseline mean bone age delays, height z scores, Tanner stages, predicted adult heights, growth rates, and midparental heights. Four months after baseline, the treated group had a significantly greater mean increase in the height z score and sexual maturation index. At 12 months, the mean increase in the sexual maturation index remained greater in the treated group. Among treated and untreated subjects older than 17 years, there was no significant difference in the absolute height z score. Over 95% of treated subjects were satisfied with the effects of therapy. PMID- 3341307 TI - Turner syndrome and hypoplastic left-heart syndrome. PMID- 3341309 TI - Cigarette smoking among childhood cancer survivors. PMID- 3341310 TI - Treatment of patent ductus arteriosus with indomethacin. PMID- 3341308 TI - Phenobarbital increases aminophylline requirement in premature infants. PMID- 3341311 TI - Misperceptions about missing children. PMID- 3341312 TI - Acute transverse myelitis associated with ECHO type 5 infection. PMID- 3341313 TI - So what's good about sports? PMID- 3341314 TI - Toward a clinical subgrouping of hyperactive and nonhyperactive attention deficit disorder. Results of a comprehensive neurological and neuropsychological assessment. AB - We studied 32 boys with attention deficit disorder (ADD)--21 with hyperactivity, and 11 without hyperactivity. The ADD group with hyperactivity had significantly more neurological and cognitive abnormalities and a higher frequency of prenatal and neonatal abnormalities. It seems that hyperactivity is an important determinant of the degree of neurological and cognitive involvement in children with ADD. It also seems that a cause of "early" brain insult is more likely when hyperactivity is present. PMID- 3341315 TI - Elevated serum iron concentration in adolescent alcohol users. AB - Alcohol is a frequently abused drug among adolescents. In adults, alcohol alters iron metabolism, predisposing to excess hepatic iron storage and, possibly, liver damage. The purpose of this study was to determine whether alcohol is associated with an elevated serum iron concentration and transferrin saturation in adolescents, and to determine the contribution of oral contraceptive use to these abnormalities. Adolescents (591 male and 614 female) aged 16 to 19 years, who participated in the first National Health and Nutrition Examination Survey from 1971 to 1973, were grouped according to their reported frequency of alcohol intake. Drinking frequency was associated with serum iron concentrations in boys and girls, and with total iron-binding capacity, transferrin saturation, and hemoglobin concentration in boys. Alcohol use was associated with an elevated serum iron concentration only in oral contraceptive nonusers. Adolescents who use alcohol have an elevated serum iron concentration, and male alcohol users have an increased transferrin saturation as well. These abnormalities may be precursors of hepatic iron overload and chronic liver damage. PMID- 3341316 TI - Prenatal lidocaine and the auditory evoked responses in term infants. AB - We examined the effects of maternal lidocaine hydrochloride anesthesia on the brain-stem auditory evoked responses (BAERs) in neonates born by cesarean delivery. Sixteen term neonates were enrolled in the study. Eight neonates were delivered by cesarean section following lidocaine anesthesia, and eight were delivered by spontaneous vaginal delivery without maternal anesthesia. A BAER was obtained on all of the neonates on the first day of life. A significant delay was noted in the central neural component of the BAER at 90 dB. The wave I through V interpeak latency for both ears was noted to be 5.3 ms for the neonates exposed to lidocaine and 4.9 ms for the controls. PMID- 3341317 TI - The effect of iron therapy on the exercise capacity of nonanemic iron-deficient adolescent runners. AB - Iron-deficiency anemia impairs exercise capacity, but whether nonanemic iron depletion decreases endurance performance is unclear. In 14 iron-deficient (serum ferritin level, less than 20 micrograms/L [less than 20 ng/L])nonanemic runners, hematologic and treadmill running values were followed up during a competitive season. Following a four-week control period, runners were treated for one month in a double-blind protocol with ferrous sulfate (975 mg/d) or placebo. During treatment, the mean ferritin level rose from 8.7 to 26.6 micrograms/L (8.7 to 26.6 ng/mL) in those patients taking iron and fell from 10.6 to 8.6 micrograms/L (10.7 to 8.6 ng/mL) in the placebo group. Treadmill endurance times improved significantly in the iron-treated runners compared with controls. Endurance time declined in all seven controls (range, 0.07 to 1.30 minutes), while six of seven iron-treated subjects improved their performance (range, 0.03 to 1.92 minutes). No significant differences in maximal or submaximal oxygen consumption, ventilation, or heart rate were observed between the groups except for a 4% increase in maximum oxygen consumption during placebo treatment. These data indicate that nonanemic iron deficiency impairs exercise performance but does not influence gas exchange or cardiac measures. PMID- 3341318 TI - The inability of a temperature-sensitive pacifier to identify fevers in ill infants. AB - We assessed the utility and accuracy of a temperature-sensitive pacifier in screening for fever in ill children under 2 years of age. Of 189 candidates for study, 83 (42%) did not use pacifiers, and of the 106 who did, 25 (24%) could not sustain a suck for five minutes of direct observation. Among those 81 children who could sustain five minutes of sucking, only two of 20 children with rectal temperatures above 100 degrees F (37.8 degrees C) were correctly identified as febrile. Furthermore, seven of eight children with temperatures of 102 degrees F (38.9 degrees C) or greater were incorrectly identified as being afebrile. There were no false-positive fever assessments in afebrile infants. The temperature sensitive pacifier tested in this study does not accurately identify fevers in most infants who are shown to have fevers by rectal temperature determination. The use of this pacifier for screening fever in ill infants cannot be recommended. PMID- 3341319 TI - Neuron-specific enolase in comatose children. AB - Sequential examination of neuron-specific enolase in cerebrospinal fluid and serum was performed in 20 comatose children with acute encephalitis, acute encephalopathy, or Reye's syndrome. Neuron-specific enolase activities corresponded to the degree of brain damage. As neuron-specific enolase levels increased to greater than 80 ng/mL, patients had more severe impairment or died. Neuron-specific enolase may be a useful marker for evaluating the degree of neuronal damage and prognosis. PMID- 3341320 TI - Beneficial effect of blood transfusion in children with sickle cell chest syndrome. AB - Reports in the 1970s suggested that acute chest syndrome (ACS) in children with sickle cell disease is usually due to bacterial infection. Studies in adults and more recently in children, however, showed that proved bacterial infection occurs in a minority of these patients and that vascular occlusion is the main pathologic process. In a retrospective study of 32 episodes of ACS in children, a definite bacterial infection was found in 3% (one patient), possible bacterial infection in 11% (four patients), and a possible mycoplasma in 13% (five patients). With the intent to dilute sickle cells, 23 patients received blood transfusion within 24 hours after hospital admission; all showed a dramatic clinical and roentgenographic improvement. Of the nine patients who did not receive a transfusion after hospital admission, the conditions of five patients deteriorated but improved after "late" transfusion; three patients showed slow improvement, and only one patient improved within 48 hours. From this we conclude that vascular occlusion might be the main process in ACS and that early blood transfusion may be valuable in shortening the course and decreasing mortality. The low hemoglobin value at presentation in our patients makes dilution of sickle cells possible by packed red blood cell transfusion rather than exchange transfusion. PMID- 3341321 TI - Pitfalls in the use of clinical asthma scoring. AB - We evaluated the correlation of the Wood-Downes-Lecks clinical asthma score (CAS) with outcome in 210 consecutive known asthmatic children presenting to an urban emergency department for treatment of acute asthma. All children received standard treatment consisting of administration of beta-adrenergic agents and theophylline compounds. Clinical asthma scores were assigned before each treatment phase and before disposition from the emergency department. Ten-day follow-up information was collected on each patient by telephone. While no differences in pretreatment CASs were found between outcome groups, disposition CASs were found to be significantly higher in patients eventually admitted to the hospital as opposed to those discharged home. However, CASs were not effective in identifying either those patients who required prolonged hospitalization (greater than 24 hours) or those who sustained ongoing disability following discharge home from the emergency department. These data indicate that the CAS alone is not a reliable indicator of severity of acute asthma of childhood as judged by subsequent disability. PMID- 3341322 TI - Waterbed care of narcotic-exposed neonates. A useful adjunct to supportive care. AB - We describe the neonatal course of 30 antenatal narcotic-exposed newborns, half of whom were randomly assigned to nonoscillating waterbeds and half to conventional bassinets. The infants were comparable at birth regarding drug exposure, ethnicity, maternal medical factors, gestational age, growth, and severity of withdrawal at the time of onset. Evaluation of total and subscores of the abstinence syndrome showed a lower total score and a significantly lower central nervous system subscore on day 5 for infants on waterbeds. The infants on waterbeds required less medication to control symptoms. The waterbed group demonstrated a significantly earlier onset of consistent weight gain as compared with the control group. This study demonstrates that nonoscillating waterbeds are an inexpensive and effective component of supportive therapy in the care of narcotic-exposed neonates. PMID- 3341323 TI - Radiological case of the month. Giant pulmonary cyst simulating pneumothorax. PMID- 3341324 TI - Lateral positioning of the stable ventilated very-low-birth-weight infant. Effect on transcutaneous oxygen and carbon dioxide. AB - Eighteen stable very-low-birth-weight (VLBW) mechanically ventilated infants with chronic lung disease were studied to examine the effects of right and left lateral positioning in contrast to supine positioning on transcutaneous (tc) oxygen (tcPO2) and carbon dioxide measurements (tcPCO2). The neonates were studied at a median postnatal age of 31 days (range, 17 to 57 days) and had median birth weights and gestational ages of 975 g (range, 570 to 1360 g) and 27.5 weeks (range, 24 to 30 weeks), respectively. Median fraction of inspiratory oxygen was 0.32 (range, 0.23 to 0.40). The sequence of study positions was randomly determined. Sleep state as well as tcPO2 and tcPCO2 were recorded every 30 s for five minutes. A significant difference in mean tcPO2 or tcPCO2 was not detected for any of the positions. Lateral positioning may facilitate the development of midline behavior in VLBW infants. Care givers are often reluctant to position infants in side lying, however, because of concerns that ventilation or oxygenation might be compromised. We conclude that placing the stable VLBW mechanically ventilated infant in a side-lying position has no deleterious effects on oxygenation and ventilation, as measured by tcPO2 and tcPCO2, and therefore should be encouraged. PMID- 3341325 TI - Tracheal stenosis in the sick premature infant. Clinical and radiologic features. AB - Six premature infants with congenital tracheal stenosis underwent diagnostic evaluation. Clinical features and chest roentgenograms were nonspecific; difficulty with intubation was the most common clinical finding and persistent lobar collapse the more common radiologic finding. The diagnosis was established by bronchoscopy in all infants. In the differential diagnosis of the sick premature infant, problems with airway patency must be considered because early intervention may reduce morbidity and mortality. PMID- 3341326 TI - Narcolepsy in a pediatric population. AB - Narcolepsy, a sleep-wake disorder of unknown cause, has been reported as occurring in the pediatric population, but only two reports of cases in the literature have included polysomnographic data on children with narcolepsy. We compared the clinical and polysomnographic data on a series of eight patients 15 years of age or younger and an adult comparison group with narcolepsy. All patients presented with excessive daytime sleepiness, and no significant difference was found between groups for the incidence of cataplexy, hypnagogic hallucinations, and sleep paralysis. On polysomnographic evaluation the pediatric group had increased total sleep time, percent-stage 3/4 sleep, percent rapid eye movement sleep, and decreased stage 1 sleep, which all are expected age-related differences. The pediatric group also showed a greater degree of daytime sleepiness and an increased frequency of sleep-onset rapid eye movement periods. While pediatric patients with narcolepsy resemble adults in their mode of presentation and the incidence of accessory symptoms, the increase in severity of sleepiness highlights the importance of diagnosing narcolepsy in children as early as possible so that treatment can be initiated. PMID- 3341327 TI - X-linked infantile spinal muscular atrophy. AB - Four male infants from three sibships in an extended family were noted to have hypotonia, areflexia, and congenital joint contractures. The findings of electromyography and muscle histology were consistent with infantile spinal muscular atrophy (SMA). Pedigree analysis suggests that this disorder represents an X-linked, recessive form of SMA. Findings in similar kindreds may explain the previously reported increased male-female ratio in infantile SMA. PMID- 3341329 TI - Mothers of preterm and full-term infants on home apnea monitors. AB - We prospectively studied the stress perception of ten mothers of preterm infants on apnea monitors (birth weight, 1255 +/- 295 g) and ten mothers of term infants on monitors (3156 +/- 700 g) and compared them with 15 mothers of preterm infants (1450 +/- 305 g) and 15 mothers of term infants (3360 +/- 595 g) not on monitors. The Life Experience Survey, a stress assessment questionnaire, and the social support questionnaire of Henderson were administered to the 50 mothers. Stress perception scores were higher for mothers of infants on monitors than for mothers of infants not on monitors. Regression analyses indicated that mothers of infants on monitors experienced less perceived stress when they received greater support. Mothers of infants on monitors who experienced less stress reported greater general life satisfaction and greater satisfaction with parenting. PMID- 3341328 TI - Umbilical cord separation in the normal newborn. AB - During a 13-month period, 363 infants were followed up through the first six weeks to determine the effect of perinatal factors (birth weight, gestational age, type of delivery, and pregnancy and neonatal complications) on umbilical cord separation. Also, breast-feedings and umbilical cord care were studied. Except for cesarean section deliveries, study infants were similar to all infants (N = 1474) admitted to the same nursery during the study period. Cord separation occurred from days three to 45, with a mean of 13.9 days. Infants born by cesarean section were found to have an increased interval for cord separation when compared with infants born vaginally (mean +/- SD, 15.9 +/- 5.0 days vs 12.9 +/- 4.2 days). In this study, delays in separation of the umbilical cord beyond 3 weeks of age was not associated with an increased risk of infection. PMID- 3341330 TI - Screening programs for congenital hypothyroidism. How can they be improved? AB - High-sensitivity neonatal hypothyroid screening tests are used throughout the country. Because of low specificity, primary care physicians are faced with an abundance of false-positive results that challenge the interpreting physician with clinical, economic, and medicolegal considerations. We surveyed 154 physicians caring for Wisconsin-born infants with the highest newborn-screen thyrotropin values in a two-year period. Our results indicated that (1) confirmation of thyroid normalcy is often delayed beyond 6 weeks of age; (2) there is wide variation among physicians regarding therapeutic goals if hypothyroidism is confirmed; and (3) physicians prefer autonomy in the management of congenital hypothyroidism. Modifications in hypothyroid screening programs may include confirmatory tests by a central laboratory (that distributes filter paper with all abnormal results), provision of a management decision tree for primary care physicians, and a one-time subsidy for a visit to a pediatric endocrinologist. We suggest that these modifications may improve the long-term outcome of hypothyroid infants identified by the screening program. PMID- 3341331 TI - Nutritional factors and growth in children with sickle cell disease. AB - A study of growth and nutrition was conducted with 20 growth-retarded (GR) and 20 growth-normal (GN) preadolescent children with sickle cell disease (SCD). All children were matched for age, sex, hemoglobin disorder, and hematologic values. Ten normal children served as control subjects. Mean serum levels of retinol, retinol-binding protein, prealbumin, and zinc were significantly lower in the children with SCD than in normal children. Mean serum retinol and prealbumin levels were similar in the GR and GN sickle cell groups. Mean serum retinol binding protein levels were lower in GR than in GN patients. Serum zinc levels, somatomedin C levels, and bone age were frequently abnormal in the patients with SCD, but these factors did not correlate with growth status. It was not possible to explain the poor growth in patients with SCD in this study solely on the basis of nutritional factors. PMID- 3341332 TI - The role of sigmoidoscopy and rectal biopsy in diagnosis and management of inflammatory bowel disease: personal experience. AB - Conventional sigmoidoscopy and rectal biopsy are very useful in the diagnosis, differential diagnosis, and management of inflammatory bowel disease. The rectal biopsy is particularly important in establishing the diagnosis of Crohn's disease when the rectal mucosa is grossly normal. The sigmoidoscopy and biopsy serve to assess the response to medical therapy in inflammatory bowel disease and are important adjuncts to colonoscopy in surveillance for dysplasia and carcinoma in patients with ulcerative colitis. Sigmoidoscopy is quick, requires no preparation, is cost effective, and the biopsies are extremely safe with the use of the cupped bronchoscopic forceps. PMID- 3341333 TI - Small colon polyps. AB - One thousand forty-eight small (up to 6 mm) colorectal polyps, removed during colonoscopy, have been analyzed. Sixty-one percent of these small polyps were neoplastic, the remainder being equally divided between hyperplastic polyps and polypoid mucosa with normal-appearing glands. The number of polyps was evenly distributed throughout the colon. Proximally, neoplastic polyps predominated, accounting for 73% of all polyps in the right colon. This was reversed in the distal colon where non-neoplastic polyps comprised 65% of all polyps in the rectum. The incidence of carcinoma was extremely low in small colon polyps, 0.1%. All polyps should be removed when encountered during colonoscopy due to the high prevalence of adenomas among small colon polyps. PMID- 3341334 TI - Age as a risk factor in colonoscopy: fact versus fiction. AB - Age has been assumed to be an independent risk factor in patients undergoing colonoscopy. However, this has never been specifically studied. We evaluated 302 patients 65 yr old or older, to determine the incidence of complications. We found that the risk is comparable to that of the heterogeneous patient population previously reported, except for a slightly increased incidence of delayed bleeding subsequent to polypectomy. In addition, the presence of cardiac, pulmonary, liver, or kidney disease was not found to be associated with an increased incidence of complications. Neither was there an increased risk of complications in patients undergoing colonoscopy, who had previously undergone abdominal or pelvic surgery. In summary, older patients experience the same risks as younger patients, except for post-polypectomy delayed bleeding, which may be related to atherosclerosis of the blood vessels, and appears to be more common in elderly patients. PMID- 3341336 TI - Daily gastric pH in controls and in duodenal ulcer patients: basal condition and response to treatment. AB - Gastric pH was monitored, by means of a computerized system, in healthy controls (C) and in patients with active duodenal ulcer (ADU) and inactive duodenal ulcer (IDU). The test was performed before treatment and during administration of a single dose of ranitidine 150 mg, cimetidine 400 mg, and pirenzepine 50 mg, in random sequence at 12-h intervals, (10 am, 10 pm). Under basal conditions, progressively lower median pH values were detected in ADU and IDU patients, compared with controls. A significant difference was found between C and ADU during daytime (1.38 vs. 0.85), nighttime (1.29 vs. 0.81), and 24 h (1.35 vs. 0.81) and between C and IDU during 24 h (1.35 vs. 1.11). However, no statistical difference was observed between patients with active and inactive ulcer disease. Administration of ranitidine and cimetidine significantly increased gastric pH during nighttime but not during daytime. Ranitidine, at the doses studied, proved to be more potent than cimetidine in suppressing gastric acidity. Gastric pH was unaffected by pirenzepine in most cases. PMID- 3341335 TI - Secretin provocation: gastrin results in various clinical situations. AB - Our previous secretin provocation studies in normal volunteers and unoperated duodenal ulcer patients suggested that the gastrin rise in gastrinoma may be an exaggeration of the normal response rather than paradoxical. We report further studies in various clinical settings having normogastrinemia (normal, n = 17; unoperated duodenal ulcer, n = 13; primary hyperparathyroidism, n = 7) and hypergastrinemia (postvagotomy, n = 5; hypochlorhydria, n = 7; achlorhydria, n = 10; chronic renal failure, n = 10; gastrinoma, n = 5). Under all nongastrinoma conditions, there were similar gastrin rises of 9-19% between 2 and 5 min after bolus intravenous GIH secretin (2 CU/kg), which fell to baseline by 8 min, except for chronic renal failure. In chronic renal failure, gastrin remained elevated from 7 to 30 min and was significantly different (p less than 0.05) at 10-30 min compared to all other nongastrinoma conditions except hyperparathyroidism. Peak rises occurred within 5 min in all entities, but only three gastrinoma patients had positive secretin provocation tests by the predefined criterion of a gastrin rise greater than 200 pg/ml. The results of secretin provocation in various clinical entities with and without hypergastrinemia further support the hypothesis that the gastrin rise in gastrinoma is an exaggeration of the normal response. The prolonged gastrin rise seen in chronic renal failure may be due to altered renal clearance, inasmuch as other hypergastrinemic states had responses similar to normal and duodenal ulcer. PMID- 3341337 TI - Comparison of radially sensitive and circumferentially sensitive microtransducer esophageal manometry probes in normal subjects. AB - Circumferentially sensitive microtransducer probes are commercially available for use in esophageal manometry, and may offer an advantage over radially sensitive microtransducer probes in sphincters with radial asymmetry. In order to compare performance of the two probes, we performed esophageal manometry in 30 healthy adult volunteers with both probes. In only three of 52 manometric parameters measured were differences between mean values for the two probes statistically significant. Intrasubject variability was significantly (p = less than 0.005) less with the circumferentially sensitive probe (coefficient of variation 37% vs. 53%). PMID- 3341339 TI - What the computer can do for the gastroenterologist. PMID- 3341338 TI - Esophageal involvement in pemphigus vulgaris. AB - Eight patients with pemphigus vulgaris were examined endoscopically for esophageal involvement. Most of them (seven of eight) had gastrointestinal symptoms of various types. Four of the patients had microscopical evidence of pemphigus vulgaris involving the esophagus. Three patients were found to have other diseases in their upper gastrointestinal tract accounting for their symptoms. There was no correlation between patients symptoms and macroscopic and microscopic findings. In patients with pemphigus vulgaris, endoscopy should be performed whenever gastrointestinal complaints appear, because the approaches to therapy could differ, according to the endoscopic findings. PMID- 3341340 TI - Fatal amiodarone hepatoxicity. AB - The antiarrhythmic agent amiodarone is associated with numerous adverse effects, but clinically significant liver disease is rare. A patient is described who presented with muscle weakness, hepatomegaly, and ascites following 28 months of amiodarone usage. His condition deteriorated despite discontinuation of amiodarone therapy. A postmortem liver biopsy demonstrated necrosis, fibrosis, hyalin, and phospholipid-laden lysosomal lamellar bodies. Resolution of hepatic dysfunction may not necessarily occur on withdrawal of amiodarone if irreversible damage is already established. We speculate as to the reasons for the reportedly low incidence of overt liver disease, and suggest that hepatic enzyme levels, as well as other indicators of hepatic function, such as the serum albumin concentration, be monitored indefinitely in all patients while taking amiodarone. PMID- 3341341 TI - Endoscopy of the gallbladder as control of gallstone therapy with methyl-tert butyl ether. AB - We report on a 36-yr-old woman with six gallstones measuring 2.1 cm each. Within 21 h of methyl-tert-butyl ether (MTBE) treatment, the stones had dissolved to a small amount of residue. As could be seen from cholesterol concentrations of samples of aspirated gallbladder bile and MTBE fractions, the dissolution process was slow to begin with, and gained momentum during hours 6-11, after which it decelerated. We discontinued treatment after 20 h, since the stone residue showed no change. Cholecystoscopy performed with an Edwards angioscope via a catheter showed that there were no stone remnants, but that there were flat polyps on the gallbladder wall. One hour later, we stopped the therapy. Cholecystoscopy is a useful method of assessing the results of MTBE treatment. PMID- 3341342 TI - Submucosal choledochal emphysema after transduodenal sphincteroplasty. AB - The widespread use of sphincteroplasty in the treatment of benign biliary obstruction requires that those physicians who must treat the complications associated with sphincteroplasty recognize the potential diagnostic pitfalls that may delay appropriate treatment. A case demonstrating one such potential pitfall is presented. PMID- 3341343 TI - Cutaneous pseudo abscesses: an unusual presentation of severe pancreatitis. AB - In this report, we present a 53-yr-old man with extensive subcutaneous fat necrosis due to acute pancreatitis presenting as fluctuant collections resembling large multiple abscesses. The diagnosis was suggested by examination of the wound aspirate. Findings included absence of organisms on the gram stain, presence of fat globules on wet mount, and an elevated amylase in the wound aspirate. This dramatic presentation preceded any symptoms or signs of overt pancreatitis. PMID- 3341345 TI - Sarcoidosis of the small intestine. PMID- 3341344 TI - Listeria monocytogenes peritonitis. AB - Listeria monocytogenes peritonitis in a patient with cirrhosis and simultaneous soft tissue infection is reported. Six previously documented cases are reviewed. All seven patients were bacteremic, suggesting hematogenous seeding to the peritoneum as the pathogenic mechanism. Clinical and laboratory characteristics of L. monocytogenes peritonitis are compared with peritonitis of other bacterial etiologies. PMID- 3341346 TI - Campylobacter pylori gastritis not related to periodontal disease. PMID- 3341347 TI - Campylobacter pylori and antral gastritis in children. PMID- 3341348 TI - Vanadium and sodium retention in cirrhosis. PMID- 3341349 TI - Esophageal involvement in Crohn's disease. PMID- 3341350 TI - Toxic dilation and amebiasis. PMID- 3341351 TI - Animal product consumption and subsequent fatal breast cancer risk among Seventh day Adventists. AB - Seventh-day Adventist women experience lower mortality rates from breast cancer than other white females in the United States. To evaluate the role of diet in relation to breast cancer within this unique population (more than one-half of all Adventist women are lacto-ovo-vegetarians), a nested case-control study was conducted including 142 cases of fatal breast cancer and 852 matched controls among California Seventh-day Adventist women in 1960-1980. No significant relations between the consumption of animal products (meat, milk, cheese, and eggs) and breast cancer were evident. Odds ratios of 1.00, 1.22, and 1.03 were observed for meat consumption categories of none or occasional, 1-3 days/week, and 4+ days/week, respectively. However, among those women who experienced a relatively early age at natural menopause (less than or equal to 48 years), a suggestive though nonsignificant, positive association between meat consumption and risk was noted. These relations remained unchanged after simultaneously controlling for the effects of other covariates (menstrual characteristics and obesity) via conditional logistic regression analysis. Risk was not related to age at first exposure to the vegetarian lifestyle nor to duration of exposure to the vegetarian lifestyle. PMID- 3341352 TI - Fibroadenoma and the use of exogenous hormones. A case-control study. AB - The association between fibroadenoma and the use of exogenous hormones in women aged 18-74 years was examined in a case-control study conducted in Connecticut during 1979-1981. The study population included 251 women with biopsy-confirmed fibroadenoma and 1,081 control women drawn from inpatient and outpatient general surgical services of five Connecticut hospitals. Among women under age 45 years, oral contraceptive use was negatively associated with the occurrence of fibroadenoma (age-adjusted odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.42-0.79). The odds ratio for women over age 45 years who had ever used oral contraceptives was 1.65 (95% CI = 0.58-4.68). Women over age 45 years who had ever used replacement estrogens had an elevated odds ratio for fibroadenoma (OR = 2.83, 95% CI = 1.21-6.60). The data suggest either that the effects of exogenous hormones may differ by age, or that the changing composition of exogenous hormones has brought about different associations depending upon the cohort of women. PMID- 3341353 TI - Coronary heart disease mortality in the Western Collaborative Group Study. Follow up experience of 22 years. AB - In 1960-1961, 3,154 healthy, middle-aged men were entered into the Western Collaborative Group Study, a long-term study of coronary heart disease. A 22-year mortality follow-up of this cohort in 1982-1983 accounted for almost 99% of the cohort, and determined that 214 of the men had died of coronary heart disease. The risk of coronary heart disease mortality was studied for several variables measured at baseline, i.e., Type A/B behavior, systolic blood pressure, serum cholesterol level, cigarette smoking status, and age. Using a proportional hazards regression model, systolic blood pressure, serum cholesterol level, cigarette smoking status, and age were highly significant predictors (p less than 0.001) of 22-year coronary heart disease mortality. Type A/B behavior showed no association with 22-year coronary heart disease mortality (standardized relative hazard (SRH) = 0.98, 95% confidence interval (CI) = 0.85-1.12). Systolic blood pressure, serum cholesterol, and age showed relatively consistent positive associations with coronary heart disease mortality over four successive time intervals after the baseline examination. Cigarette smoking showed a significant positive association in the first and second intervals and a nonsignificant positive association in the third and fourth intervals. Type A/B behavior was positively but not significantly associated with coronary heart disease in the first and third intervals, significantly negatively associated (SRH = 0.70, 95% CI = 0.53-0.93) in the second interval and not associated in the fourth interval. The results confirm the importance of the traditional coronary heart disease risk factors, and raise a substantial question about the importance of Type A/B behavior as a risk factor for coronary heart disease mortality. PMID- 3341354 TI - A comparison of the 12-year mortality and predictive factors of coronary heart disease among Japanese men in Japan and Hawaii. AB - The mortality and predictive factors of coronary heart disease among men of Japanese ancestry in Japan and Hawaii were compared on the basis of 12 years follow-up data using comparable methods of case ascertainment and risk factor measurements. Among 1,687 men (Japan) and 7,536 men (Hawaii) who were free of coronary heart disease and aged 45-69 at baseline examination in 1965-1968, 20 (Japan) and 123 (Hawaii) cases of fatal coronary heart disease were identified. The age-adjusted mortality rate was 40% higher in Hawaii than in Japan. The difference was not statistically significant, but consistent with earlier studies. More than half of this difference in mortality rate was attributed to different levels of known risk factors in the two cohorts. In multivariate analysis using the combined population, age, blood pressure, serum cholesterol, serum glucose, cigarette smoking, and alcohol intake (inversely) remained as significant predictors of coronary heart disease mortality. Although the associations of risk factors with coronary heart disease tended to be stronger in Hawaii than in Japan, there was no statistically significant difference in regression coefficient for any of the risk factors studied. These findings cannot be claimed to be definitive because of the small number of cases, especially in Japan. PMID- 3341355 TI - Ten-year results of hypertension care in the community. Follow-up of the North Karelia hypertension control program. AB - The development of hypertension care over the 10-year period 1972-1982 in North Karelia and a reference area was assessed using three separate random samples of the population aged 30-59 years. The results show a clear improvement in the blood pressure levels of the population and in the hypertension care in North Karelia between 1972 and 1977 when the activities of the hypertension program of the North Karelia Project were gradually implemented. Awareness of elevated blood pressure increased from 39% to 71% among men and from 60% to 87% among women. The proportion of men under antihypertensive drug treatment increased from 4% to 10% and that of women increased from 10% to 15%. After 1977, the hypertension care was maintained but no further improvements were observed in general blood pressure levels. An improvement in hypertension care started in the reference area later than in North Karelia. In spite of favorable changes, the blood pressure level of the population was still high in 1982, the mean casual value among men being 145/87 mmHg and that among women being 141/84 mmHg. It is obvious that further progress in hypertension care is needed. PMID- 3341357 TI - The onset of decline in ischemic heart disease mortality in the United States. AB - Temporal and spatial patterns of the onset of the decline in ischemic heart disease mortality in the United States for each of the 48 contiguous US states and the District of Columbia are examined for the years 1955-1978 for age-sex race-specific mortality. Mortality rates are derived from National Center for Health Statistics mortality data, and a polynomial interpolation is used to estimate intercensal population counts employing 1950, 1960, 1970, and 1980 US Census data. A quadratic regression equation is used to estimate the date of highest rate, which marks the beginning of the decline for each of the US states. The temporal distribution of the onset of the decline among men occurred primarily between 1960 and 1965. Among women, the onset of decline was more variable. Furthermore, strong and regular spatial patterns were seen among the groups examined and these impressions are supported by statistical analysis. California, Maryland, and the District of Columbia were early decliners in most groups studied, whereas states in the southeast were consistently among the last to experience the onset of decline. These patterns suggest the existence of an underlying phenomenon accounting for the spread or diffusion of the onset of decline in ischemic heart disease mortality. PMID- 3341356 TI - The risk factors for arrhythmic death in a sample of men followed for 20 years. AB - In a sample of 301 men, aged 54-62 years, who were employed in the telephone industry in New Jersey, and who were followed prospectively from 1963/1964 to 1984, 65 of 148 deaths were manifested by the abrupt occurrence of fatal ventricular arrhythmias. On multivariate analysis, the factors present at the initial examination that were significantly related to the subsequent occurrence of arrhythmic deaths were: abnormal patterns of QRS conduction; the level of blood pressure; the number of cigarettes currently being smoked; chronic myocardial ischemia; chronic airway disease; and failure to engage in any exercise or heavy physical activity. Among 28 other potential risk factors representing myocardial disorders, ventricular dysrhythmias, other disorders of cardiac rate, rhythm, conduction, and repolarization, and non-cardiac risk factors (including cholesterol level, serum uric acid level, diabetes mellitus, alcohol intake, general arteriosclerosis, other non-cardiac disease, and social, behavioral, and attitudinal variables), none significantly added to risk for arrhythmic death. The risk factors related to the subsequent occurrence of other deaths, manifested by the gradual development of circulatory failure, were significantly different from the risk factors related to arrhythmic deaths. PMID- 3341358 TI - A mortality study of a research, engineering, and metal fabrication facility in western New York State. AB - The mortality experience of 8,146 male employees of a research, engineering, and metal fabrication facility in Tonawanda, New York state was examined from 1946 to 1981. Potential workplace exposures included welding fumes, cutting oils, asbestos, organic solvents, and environmental ionizing radiation, as the result of disposal of wastes during the Manhattan Project of World War II. External comparisons with the US male population were supplemented by regional comparisons. For the total cohort, deficits were observed for all causes of death (standardized mortality ratio (SMR) = 87) and most non-cancer causes. The observed number of cancer deaths was close to expected (SMR = 99). There was an excess of connective and soft tissue cancer deaths, most notably in hourly employees hired prior to 1946. Among all hourly employees, there was an excess of respiratory cancer, which did not appear to be associated with length of employment. Mesothelioma was recorded as the cause of death for three decedents, two of whom were hourly employees who worked in production areas with high potential for asbestos exposure. The standardized mortality ratio for cirrhosis of the liver was elevated among long-term hourly employees hired prior to 1946. The roles of carbon tetrachloride exposure in the 1940s and alcohol consumption are discussed as possible contributory risk factors for the cirrhosis findings. The data do not provide evidence of radiation-induced cancers within this employee population. PMID- 3341359 TI - Intensity of follow-up. Effects on estimates in a population telephone survey with an extension of Kish's (1965) approach. AB - Information from a population telephone survey of attitudes of residents of the Province of Ontario, Canada, toward legislation to restrict smoking was used to examine the effects of intensity of follow-up on population estimates. It was found that the bias introduced to the attitude estimates by less intensive follow up was smaller than the bias introduced to estimates of sociodemographic characteristics and smoking status. An algebraic determination of the components contributing to the bias in the attitude estimates was used to investigate how the relation between smoking status and certain attitudes influenced the relation between attitude and intensity of follow-up. This required an extension of the approach described by Kish (Survey Sampling. New York: John Wiley and Sons, 1965.) PMID- 3341360 TI - The association of reproductive history, demographic factors, and alcohol and tobacco consumption with the risk of developing nausea and vomiting in early pregnancy. AB - The role of maternal risk factors in the development of nausea and vomiting in pregnancy was studied in a historical cohort of 825 women who gave birth at the University of California (Los Angeles) Medical Center during a one-year period (April 1983-March 1984). The roles of demographic factors, reproductive history, and consumption of alcohol and tobacco in affecting the risk of developing nausea and vomiting were studied using both bivariate and multivariate statistical methods. Interpretations of the statistical analyses identify three risk factor associations correlated with decreased risk of nausea and vomiting and one factor associated with increased risk. The most apparent pattern was that women who were ethnically white, of white collar or professional occupation, and who consumed alcohol prior to conception, were at decreased risk for nausea and vomiting. The second pattern of decreased risk consisted of women over 35 years old with a history of infertility for one or more years prior to the current conception. The third low-risk pattern consisted of women without a history of nausea during prior pregnancies. The only factor associated with an increased risk was housewife occupational status. The results of this study are consistent with an endocrinologic model for the etiology of pregnancy-induced nausea and vomiting. PMID- 3341361 TI - Physical fitness and cardiovascular disease mortality. The US Railroad Study. AB - The relation between physical fitness and cardiovascular disease mortality was examined in US railroad workers, as a part of the Seven Countries Study. A cohort of 3,043 white, middle-aged men initially aged 22-79 years were first examined in 1957-1960 and re-examined in 1962-1964. Men with clinically diagnosed cardiovascular disease (n = 465) were excluded from this study. This cohort was followed until death or 1977. Mortality was monitored through the Railroad Retirement Board. Physical fitness was ascertained by a sub-maximal treadmill test administered in a Pullman Car converted to a survey laboratory. Exercise heart rate was directly and significantly related to coronary heart disease mortality, cardiovascular disease mortality, and all-cause mortality after adjusting for age. These relations were greatly attenuated when adjusted for blood pressure level. The risk for coronary heart disease when an exercise test heart rate of 135 beats per minute was compared with a rate of 105 beats per minute was 1.43, after adjusting for age, and 1.20, after adjusting for blood pressure, serum cholesterol levels, and smoking, as well as age. Results from this study suggest that middle-aged men with lower levels of physical fitness, as shown by higher sub-maximal exercise test heart rates, are at greater risk of dying of coronary heart disease, cardiovascular disease, and all causes in an average follow-up of 20 years. This greater risk is largely due to higher blood pressure levels. PMID- 3341362 TI - A large outbreak of acupuncture-associated hepatitis B. AB - An epidemiologic investigation of an acupuncturist's practice in Rhode Island identified 35 patients who were infected with hepatitis B virus during 1984. Of 366 patients seen by the acupuncturist during 1984, 316 (86%) completed questionnaires and submitted serum for hepatitis B serology. Use of tests for immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) identified 17 case-patients who otherwise may have gone undetected. Thirty-four of the 35 case-patients were treated in only one of the two clinics run by the acupuncturist. Patients who received a greater number of acupuncture needles during their treatment course were more likely to have been infected; the attack rate for patients who received less than 150 needles was 9%, compared with 33% for patients who received greater than or equal to 450 needles (p less than 0.001). Attack rates were higher during a one-month period when the index case patient was more likely to have been viremic than during any other period in 1984 (relative risk = 4.1, 95% confidence interval = 2.3-7.3). While observing the acupuncturist's technique, the investigators noted several potential mechanisms for needle contamination. This study highlights the potential for transmission of hepatitis B in situations of repeated needle use. PMID- 3341363 TI - Asymmetric stratification. An outline for an efficient method for controlling confounding in cohort studies. AB - Confounding is usually controlled by either cross-stratification or multivariate modeling. The first approach is simple and intuitive, but it is not practical for controlling many factors. The second approach, although less intuitive, may provide a more efficient means for controlling many confounders, but its ability to control confounding depends on the appropriateness of the chosen model. Hybrid methods based on a multivariate confounder score or a propensity score combine the favorable characteristics of both methods and may be better suited for controlling many confounders. However, the resulting strata are defined by subranges of a multivariate model, and, therefore, may possess little intrinsic meaning. The authors propose the principle of asymmetric stratification to control efficiently a number of confounders in cohort studies while retaining the intuitive appeal and general framework of cross-stratification. The proposed method resembles a propensity score analysis but does not use a multivariate model to define the strata. Instead, strata are defined by the categories of only a subset of the original potential confounders. The authors also demonstrate how our proposed method can be implemented by an application of classification and regression trees (CART) (recursive partitioning), as outlined by Breiman et al. (Classification and Regression Trees. Belmont, CA: Wadsworth, 1984). Computer simulations and an actual example suggest that the proposed method is a potentially simpler alternative to the standard propensity score analysis. Specific recommendations on how the proposed method can be improved are also presented. PMID- 3341364 TI - Convergence of immigrant suicide rates to those in the destination country. AB - Factors influencing the 1969-1973 suicide rate in 25 immigrant groups in Canada were investigated. Standardized mortality ratios (SMRs) were calculated for each group relative to the suicide rates in the origin country populations. Compared with their origin countries, immigrant females exhibited a significant increase in suicide rates (SMR = 1.11, p less than 0.01), whereas immigrant males did not (SMR = 0.98). Another set of standardized mortality ratios were then calculated for both origin and immigrant populations using the Canadian native-born rates as the standard. For the majority of immigrant groups, the standardized mortality ratios were significantly different from the ratios of their corresponding origin country populations, with 60% of the female immigrant groups and 41% of the male immigrant groups exhibiting higher ratios. Considerable variation was observed in the immigrant standardized mortality ratios, with a significant proportion of this variability being associated with the suicide rates in the origin countries (males r = 0.60, p less than 0.01; females r = 0.47, p less than 0.05). Using the standardized mortality ratios based on the Canadian native-born rates, the degree of "convergence" of immigrant suicide rates to the Canadian native-born rates was examined. Overall, significant convergence occurred for both sexes (p less than 0.01), with the immigrant suicide rates converging 40% of the initial difference between the standardized mortality ratios for the origin country and the Canadian native-born. PMID- 3341366 TI - Can familial aggregation of disease be explained by familial aggregation of environmental risk factors? AB - Although familial aggregation has been shown for many if not all diseases, it is often difficult to determine whether such aggregation is due to shared genes or shared environmental factors. The authors examine the effect of familial aggregation of environmental risk factors on familial aggregation of disease when there is no genetic susceptibility. An environmental risk factor with a relative risk (R) for disease and population exposure frequency (f) is assumed to be clustered among siblings with varying degrees of sibling correlation in exposure (c). The impact of varying R, f, and c is examined on two common measures of familial aggregation: the relative risk of disease for siblings of cases compared with siblings of controls, and the sibling recurrence risk. It can be shown that both measures increase with increasing R and c, but decrease at high levels of f. However, even in the face of complete correlation in exposure among siblings (c = 1), environmental risk factors that have values of R less than 10 lead to modest sibling relative risks (ranging from 1 to 2) and low recurrence risks. Similar findings are obtained when familial aggregation of two additive environmental factors is considered. Because many diseases show higher sibling relative risks and recurrence risks, this analysis suggests that simple familial clustering of environmental factors is unlikely to account entirely for familial aggregation of disease, and that genetic factors ought to play an important role in causing familial aggregation. PMID- 3341365 TI - Adjusting morbidity ratios in two communities using risk factor prevalence in cases. AB - Available data on cancer incidence for 1969-1971 showed statistically elevated rates for breast cancer in St. Louis Park, Minnesota, a community with creosote contamination of the water supply, when compared with the rest of the Minneapolis St. Paul area taken as the reference population. In order to assess the effect of other known risk factors for breast cancer, 75 persons with breast cancer in each of the two populations were interviewed to obtain frequencies of known risk factors. An adjusted morbidity ratio in the two populations and an expected case rate in the exposed community were calculated from these frequencies, using relative risk values from the medical literature. The adjusted morbidity ratio was less than 1.0, and the observed rate was almost identical to the new expectation, although the age-adjusted rates alone had suggested a significant difference in incidence. This method makes use of relative risks from published studies rather than those associated with local cases and controls. It allows more refined evaluation of differences in cancer rates between communities than can be provided by age- and sex-specific calculations alone, and may allow use of available statistics in situations where cost, temporal considerations, or population size do not favor large new studies. PMID- 3341367 TI - Effect of contact letter on control response rates in cancer studies. AB - Our analysis of response rates for community controls approached in a retrospective study of melanoma indicates that there was an 11 per cent improvement in response rate when the contact letter was changed from inviting participation in a "healthy study" with no mention of cancer to a format which explicitly explained that the study concerned cancer. This improvement was observed for all age-sex groups except younger males. The result suggest that higher response rates may be achieved in studies of cancer if fuller disclosure of the study purposes is made. PMID- 3341368 TI - Re: "The AIDS epidemic in New York City, 1981-1984". PMID- 3341369 TI - Re: "Nonspecific inflammatory bowel disease and smoking". PMID- 3341370 TI - Re: "Do pressurized bronchodilator aerosols cause death among asthmatics?". PMID- 3341371 TI - Divalent cations induce protofibril gelation. AB - Soluble fibrin oligomers (protofibrils) undergo phase change merely by adding 1-2 mM Ca2+ or 25-100 microM Zn2+. The cation-induced "protofibrin" clots appear similar to normally formed fibrin gels. Maximal clot turbidity of protofibrin gels increases with cations in a concentration-dependent manner. Magnesium (less than 0.5 mM) is ineffective in inducing protofibril gelation. Turbidity and degree of polymerization (DP) [indirectly expressed as AT (activation time)] appear to be positively correlated, regardless of whether the divalent cation is Ca2+ or Zn2+. Cross sections of Ca2+-induced protofibrin fibers are approximately 6-18-fibrin-monomers-thick. With both Ca2+ and 40 microM Zn2+, fiber cross section increases to 30-50 monomers thick. Negatively stained Zn2+-and Ca2+ induced protofibrin gels exhibit banding periodicity of approximately 240 A, similar to that of normally generated fibrin gels. Regions of lateral merging of individual segments of the protofibrin leads to increased cross section of the fiber and forms a branch required for gelation. These findings indicate that the rate of coagulation and the ultimate thickness of the fibers both relate to lateral associative processes of protofibrils, which are augmented by physiologic concentrations of 2+ and Zn2+. PMID- 3341372 TI - Effect of methotrexate on the deoxyuridine suppression test: results with different cell preparations. AB - Recently, the deoxyuridine suppression test was used to detect folate deficiency. Several cell preparations were used in this test, and the sensitivity of the test seems to vary with them. We used whole blood (micro-dU test) and bone marrow cells for the deoxyuridine suppression test, and the effects of methotrexate were compared. [3H]Thymidine incorporation into DNA was highest when the concentration of methotrexate was 1 microM in the whole blood culture and bone marrow culture. Methotrexate concentrations from 100 nM to 1 mM did not affect the results of the micro-dU test. However, the bone marrow deoxyuridine test became abnormal with methotrexate, and the abnormality in test values was corrected by the addition of N5-formyltetrahydrofolate. Differences in the results between the micro-dU test and the bone marrow deoxyuridine suppression test seem to represent specificity of each dU test. PMID- 3341374 TI - Effects of dietary fish oil on serum lipids and blood coagulation in peritoneal dialysis patients. AB - The effects of a daily fish oil supplement rich in eicosapentaenoic acid were studied in 11 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Serum lipids, platelet aggregation studies, and template bleeding times were determined before and after 4 weeks of fish oil treatment. The lipid studies were repeated approximately 20 weeks after stopping fish oil supplement. At the end of the treatment period, serum triglycerides (mean +/- SEM) decreased from 297 +/- 42 to 211 +/- 29 mg/dL (P less than .01), high density lipoprotein (HDL) cholesterol fell from 45 +/- 3 to 41 +/- 3 mg/dL (P less than .05), and low density lipoprotein (LDL) cholesterol increased from 172 +/- 16 to 208 +/- 19 mg/dL (P less than .05). After discontinuing the fish oil supplement, the triglycerides increased to 278 +/- 39 mg/dL, which was no different than the value before fish oil treatment. No significant changes occurred in template bleeding time (TBT), platelet count, hematocrit, or platelet aggregation response. Clinically important uremic bleeding was not apparent. We conclude that in CAPD patients a fish oil supplement favorably effects hypertriglyceridemia and can be ingested without promoting uremic bleeding. The likely beneficial impact on atherogenesis resulting from the lowering of the triglycerides may, however, be counteracted by concomitant changes in HDL- and LDL-cholesterol. PMID- 3341373 TI - Granulopoietic differentiation in long-term bone marrow cultures from children with congenital neutropenia. AB - The capacity of granulopoietic precursor cells (CFU-GM) to differentiate in vitro was evaluated in five children with congenital neutropenia using short-term colony assays and long-term marrow cultures. In all five children, methylcellulose assays revealed normal numbers of CFU-GM, which displayed an appropriate response to various sources of GM-CSF and differentiated up to the polymorphonuclear leukocyte state (PMN). In contrast, neutrophil PMN were not observed in long-term bone marrow cultures from three patients, despite a normal production of CFU-GM, myeloblasts, and promyelocytes during the 5-6 week culture period. Thus, in these patients, the characteristic "block" in granulocytic maturation observed in vivo was reproduced in vitro in long-term cultures. Granulocytic differentiation proceeded normally in long-term cultures from the two other patients, thus indicating heterogeneity in the expression of the defect. These results might indicate abnormal interactions between stromal and hematopoietic cells in long-term marrow cultures from some patients with congenital neutropenia. Furthermore, our results showed some correlation between the granulocytic defect in vitro and the clinical outcome in vivo. PMID- 3341375 TI - Peritoneal eosinophilia in patients on continuous ambulatory peritoneal dialysis: a prospective study. AB - A prospective study on peritoneal eosinophilia was conducted in 23 continuous ambulatory peritoneal dialysis (CAPD) patients for a mean period of 7.9 months. Peritoneal eosinophilia as defined by peritoneal eosinophil count exceeding 100/mm3 was found in 60.8% of patients. Most developed peritoneal eosinophilia within 3 months of the initiation of dialysis, although the phenomenon could occur as early as one day or as late as 6 months after dialysis. Fifty-seven percent of those with peritoneal eosinophilia also had peripheral blood eosinophilia. Although most peritoneal eosinophilic episodes subsided in a month, in one patient the process grumbled on for 150 days. The number of peritonitis episodes was not significantly different between patients with peritoneal eosinophilia and those without. The only distinction between the two groups of patients was that those who developed peritoneal eosinophilia had a significantly (P = .002) higher serum IgE concentration initially as well as throughout the period of observation. PMID- 3341376 TI - Exertional heat stroke and acute renal failure in a young woman. AB - Strenuous exercise leading to heat stroke is known to cause rhabdomyolysis and acute renal failure in men, but there are no reports of this environmental illness in otherwise healthy women. We report the first case of heat and exercise induced acute renal failure in a young nonacclimated adult female following intense exertion in the Grand Canyon. This individual displayed the typical clinical features of exertional heat stroke including hyperpyrexia, CNS disturbance, rhabdomyolysis, oligoanuric acute renal failure, and disseminated intravascular coagulopathy. The pathophysiology is discussed as well as sexual differences in response to heat and exercise. The specific factors that may have predisposed this young woman to heat stroke from exertion are identified. PMID- 3341377 TI - Acquired cystic kidney disease: occurrence in patients on chronic peritoneal dialysis. AB - Acquired cystic kidney disease (ACKD) is a well-known complication of long-term hemodialysis. To the best of our knowledge, only six patients on continuous ambulatory peritoneal dialysis have been reported to develop this disease. We herein report two such cases, and concluded that the morphology of ACKD seems to be independent of the type of dialysis and that hemodialysis is not necessary for the development of ACKD. PMID- 3341378 TI - Hematuria and proteinuria in a patient with ankylosing spondylitis. PMID- 3341379 TI - Uniparental disomy: a rare consequence of the high rate of aneuploidy in human gametes. PMID- 3341380 TI - Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. AB - To resolve uncertainty concerning the inheritance of the perinatal lethal form of osteogenesis imperfecta (OI type II), we collected family data and radiographs for 71 probands and analyzed the collagens synthesized by dermal fibroblastic cells cultured from 43 of the probands, 19 parental pairs, and single parents of each of four additional probands. In 65 families for which there were complete data on sibship size, there was recurrence of the OI type II phenotype in five families such that six (8.6%) of 70 sibs were affected. In two families with recurrence, the radiographic phenotype was milder than that for the remainder; and one of those families was consanguinous, suggesting autosomal recessive inheritance. In the remaining three families there was no evidence of consanguinity, but in one of them the structure was compatible with gonadal mosaicism in the mother. In studies of collagens synthesized by cells from 43 infants, we identified two probands with separate rearrangements in an allele of one of the genes of type I collagen; but in the rest there were subtle mutations that disrupted the normal triple-helix structure of type I collagen molecules. In two probands we identified de novo mutations; in 16 additional families cells from the parents made only normal collagens, compatible with new mutations in their offsprings. These findings indicate that the OI type II phenotype is biochemically heterogeneous, that the majority result from new dominant mutations in the genes encoding type I collagen, and that some recurrences can be accounted for by gonadal mosaicism in one of the parents. PMID- 3341381 TI - Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island. AB - To determine the nature of the genetic component controlling susceptibility to leprosy and its subtypes, complex segregation analysis, by means of the POINTER strategy, was performed on 27 multigenerational pedigrees from Desirade, a Caribbean island where leprosy is highly prevalent. The results are consistent with the presence of a recessive or codominant major gene controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Under the major-gene model, tests of homogeneity to check for internal consistency of the sample and to compare subsamples according to an epidemiological criterion, the place of residence of the probands, were conducted; results of none of these tests were significant. However, we have noted that information on 3 generations (nuclear families with a pointer to the sibship) is of major importance for detecting major gene(s). Besides, the discrepancy in the results obtained in separate analyses of the family subsamples defined by the place of residence of the probands is discussed in terms of possible genetic and/or environmental differences. Referring to experimental data and previous studies, we suggest that the gene for susceptibility to leprosy per se and that for susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae. PMID- 3341382 TI - Assessment of aneuploidy in the human female by using cytogenetics of IVF failures. AB - The karyotype was determined for 201 unfertilized human oocytes recovered from 87 women participating in an in vitro fertilization program. Their mean age was 30.6 years (range 22-40 years). Thirteen oocytes did not exhibit the first polar body and were found to be in the first-metaphase stage. The remaining 188 eggs were assessed as mature and classified into two groups according to the supposed origin of fertilization failure. The overall incidence of aneuploidy was 18.6%. This rate was higher in the group of unexplained fertilization failure (22.5%) than in the group of fertilization failure due to sperm deficiency (10.2%). This may reflect a relationship between the genomic constitution of the oocyte and its fertilizability. On the other hand, no increase of aneuploidy was observed with maternal aging. PMID- 3341384 TI - A new statistical test for linkage heterogeneity. AB - A new, statistical test for linkage heterogeneity is described. It is a likelihood-ratio test based on a beta distribution for the prior distribution of the recombination fraction among families (or individuals). The null distribution for this statistic (called the B-test) is derived under a broad range of circumstances. Two other heterogeneity test statistics--the admixture test or A test first described by Smith and Morton's test (here referred to as the K-test)- are also examined. The probability distribution for the K-test statistic is very sensitive to family size, whereas the other two statistics are not. All three statistics are somewhat sensitive to the magnitude of the recombination fraction theta. Critical values for each of the test statistics are given. A conservative approximation for both the A-test and B-test is given by a chi 2 distribution when P/2 instead of P is used for the observed significance level. In terms of power, the B-test performs best among the three tests over a broad range of alternate heterogeneity hypotheses--except for the specific case of admixture with loose linkage, in which the A-test performs best. Overall, the difference in power among the three tests is not large. An application to some recently published data on the fragile-X syndrome and X-chromosome markers is given. PMID- 3341385 TI - Steinberg's new paternity probability. PMID- 3341383 TI - Chromosomal localization and racial distribution of the polymorphic human dihydrofolate reductase pseudogene (DHFRP1). AB - The human dihydrofolate reductase (DHFR) gene family comprises one functional gene and at least four intronless processed pseudogenes. The functional DHFR gene is on chromosome 5, and DHFRP4 is on chromosome 3. Using in situ hybridization, we have now localized the functional DHFR gene to the region q11.1-q13.3 on chromosome 5. By genomic DNA analysis of a panel of human X rodent somatic-cell hybrids, we determined the chromosomal assignment of the DHFRP1 pseudogene to chromosome 18 and that of the DHFRP2 pseudogene to chromosome 6. The DHFRP1 pseudogene exhibits a novel form of polymorphism in humans in that it is present in the DNA of some individuals and absent in that of others. We investigated the racial distribution of this pseudogene in five racial groups. The allelic frequency as defined by analysis of 180 chromosomes was found to be 94% in Mediterraneans, 77% in Asian Indians, 67% in Chinese, 57% in Southeast Asians, and 32% in American blacks. These data suggest that the transposition of this "perfect" pseudogene occurred prior to the inception of the human racial groups. PMID- 3341386 TI - Well-being, hypertension, and indapamide. Proceedings of the XVth international meeting. November 8, 1986, Rome, Italy. PMID- 3341387 TI - Effect of indapamide on an experimental model of cerebral ischemia in hypertensive rats. AB - This study quantified the immediate general hemodynamic events following the bilateral carotid ligation-induced cerebral ischemia in normotensive and spontaneously hypertensive rats. The influence of treatment with indapamide was evaluated. In normotensive rats, hemodynamic values remained unchanged during the 10 minutes following the carotid ligation. In spontaneously hypertensive rats, arterial pressure values immediately and significantly (p less than 0.01) increased, up to 50 percent during the 10 minutes following the carotid ligation. Heart rate was unchanged. Indapamide at a short-term 3 mg/kg intraperitoneally, chosen in order to give a minimal (nonsignificant) antihypertensive effect in spontaneously hypertensive rats, significantly (p less than 0.01) reduced the bilateral carotid ligation-induced vasopressor response, whereas heart rate remained unchanged. The results presented here show that in spontaneously hypertensive rats, but not in normotensive rats, bilateral common carotid ligation induces an immediate and strong increase in arterial pressure values. These results compare with the previously described differences in cerebral ischemia-induced disorders in normotensive and hypertensive rats. Finally, indapamide, an antihypertensive agent that decreases vascular reactivity, significantly inhibits the carotid ligation-induced vasopressive response in hypertensive rats. PMID- 3341389 TI - Cardiac prognosis in hypertensive patients. Incidence of sudden death and ventricular arrhythmias. AB - The cardiac prognosis of hypertensive patients has been able to be precisely determined over the last 20 years as a result of large-scale epidemiologic surveys. The incidence of ischemic heart disease and the importance of left ventricular hypertrophy have been clearly defined in the literature. In contrast, the incidence of sudden death and ventricular arrhythmias has been poorly taken into account, although hypertension increases the risk of sudden death to the same degree as coronary artery disease. The relative risk increases progressively as a function of the quintiles of distribution of blood pressure, reaching a value of 3.2 for the highest quintile. There is also a significant correlation between hypertension and ventricular arrhythmias. Hypertensive subjects with other cardiovascular risk factors such as hypercholesterolemia or smoking and with ventricular extrasystoles, reflecting the presence of silent ischemia, can be considered to be at high risk of cardiac death. PMID- 3341388 TI - Effects of indapamide on the quality of life of hypertensive patients. AB - This study analyzed the variation in the parameters characterizing the quality of life and well-being of hypertensive patients treated with indapamide. Thirty patients (10 men and 20 women; mean age, 52.5 +/- 2.1 years, SEM) were selected after a three-week observation period during which patients received placebo. They all had essential hypertension, defined as a diastolic blood pressure between 95 and 120 mm Hg. After the three-week placebo treatment period, indapamide was prescribed as single-agent therapy at a dose of one tablet per day (2.5 mg) for three months. The quality of life and the feeling of well-being of the treated subjects were analyzed on the basis of two self-assessment scales completed by patients and on the responses to a clinical observation scale completed during the consultation by the doctor. The decrease in blood pressure was significant (p less than 0.01) by the first month of treatment and the blood pressure was controlled (diastolic blood pressure less than 90 mm Hg) in 79.3 percent of patients by the third month. Statistical analysis of the modifications in the different scores demonstrated a significant improvement between the start and the end of the indapamide treatment period for the three types of scales (p less than 0.01). Analysis of the results also confirmed the homogeneous and significant concordance between the improvement in the responses to the doctor and patient scales. These results on the improvement in quality of life and well being observed with indapamide demonstrate the importance of taking these aspects into consideration in the drug treatment for permanent essential hypertension. PMID- 3341390 TI - Cardiovascular effects of indapamide in hypertensive patients with or without renal failure. A dose-response curve. AB - Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients--five with normal renal function--were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular end diastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate the antihypertensive effect of indapamide. PMID- 3341392 TI - Short staffing on trial. PMID- 3341391 TI - Hypertension in elderly patients. A comparative study between indapamide and hydrochlorothiazide. AB - Diuretic therapy is still regarded as the first-step approach in elderly patients with benign or moderate arterial hypertension. Traditional preparations such as thiazides, or potassium-sparing agents, are not devoid of significant side effects, however. Indapamide, a nonthiazide diuretic, has been shown to reduce blood pressure at low doses, in several clinical reports. In the present study, the effect of indapamide (2.5 mg per day) was compared with that of hydrochlorothiazide (50 mg per day) on blood pressure and serum chemistry of 47 elderly hypertensive patients (ages 65 to 91). After a six-week placebo-treatment period, patients were randomly assigned to receive either indapamide or hydrochlorothiazide. At that moment, blood pressure of patients in the supine position averaged 185 +/- 2/107 +/- 2, and 181 +/- 3/102 +/- 2 mm Hg, in the indapamide and hydrochlorothiazide groups, respectively. After 48 weeks of therapy, blood pressure was 162 +/- 3/89 +/- 2 and 170 +/- 2/94 +/- 2 mm Hg in the same groups, respectively. Serum sodium levels remained unchanged in indapamide-treated patients, but decreased progressively from 141 +/- 1 to 134 +/ 1 meq/liter in hydrochlorothiazide-treated patients. Serum potassium levels decreased from 4.50 +/- 0.12 to 4.04 +/- 0.10 meq/liter in indapamide-treated patients, whereas in the patients receiving hydrochlorothiazide, kalemia decreased from 4.23 +/- 0.09 to 3.33 +/- 0.01 meq/liter. Finally, serum uric acid levels did not increase significantly in patients receiving indapamide, whereas it rose from 6.5 +/- 0.4 to 8.7 +/- 0.3 mg/dl in patients treated with hydrochlorothiazide. In conclusion, indapamide resulted in a better control of systolic and diastolic blood pressure in this group of elderly hypertensive patients. In addition, the effect of each drug on blood chemistry differed markedly: indapamide failed to alter significantly the serum ionic composition, whereas hydrochlorothiazide was associated with both hyponatremia and hypokalemia. PMID- 3341393 TI - Primary fever. PMID- 3341394 TI - What keeps nurses in nursing. 3,500 nurses tell their stories. PMID- 3341395 TI - Saving the skin from tape injuries. PMID- 3341397 TI - California AJN jobfocus. Striking gold. PMID- 3341398 TI - Diagnosing the cat. PMID- 3341396 TI - What patients on home oxygen therapy want to know. PMID- 3341399 TI - Progesterone profiles in luteal phase defect cycles and outcome of progesterone treatment in patients with recurrent spontaneous abortion. AB - The existence of luteal phase defect has been the focus of much debate, mainly because of inconsistencies in its diagnosis and management. This study was performed to compare progesterone profiles in women with luteal phase defect with those of women with normal cycles and to establish a discriminatory level of serum progesterone that may aid in the diagnosis of this condition. Compared with patients with luteal phase defect cycles, women with normal cycles produced significantly more progesterone in the luteal phase. The serum progesterone level (less than or equal to 21 nmol/L) was the optimal discriminatory level between luteal phase defect and normal cycles and provided a diagnostic test with 70% sensitivity and 71% specificity. In women with recurrent abortion, the incidence of luteal phase defect was 40%, but with treatment 81% of pregnancies were successful. The findings in this study support the existence of luteal phase defect as a clinically significant entity in recurrent first-trimester spontaneous abortion and one that can be treated successfully with the administration of progesterone. The histologic diagnosis of luteal phase defect may also be confirmed with serum progesterone. PMID- 3341400 TI - Unrecognized small vesicovaginal fistula as a cause of persistent urinary incontinence. AB - Three cases of persistent urinary incontinence from unrecognized small vesicovaginal fistula after abdominal hysterectomy for benign gynecologic disease are presented. Visualization of urine in the posterior fornix was suggestive; diagnosis was confirmed by methylene blue test and cystoscopy. Two patients had undergone interval Marshall-Marchetti-Krantz operations for suspected stress related urinary incontinence. An extensive literature survey confirms that the vesicovaginal fistula were an unlikely complication of the Marshall-Marchetti Krantz procedure. PMID- 3341401 TI - Bowel obstruction in patients with ovarian cancer: a search for prognostic factors. AB - Patients with concomitant ovarian cancer and bowel obstruction were studied in an effort to find objective prognostic factors predictive of patient outcome. A total of 62 patients were followed from 31 to 354 weeks, and a total of 20 variables were considered in the analyses. At the end of the study 49 patients were dead of their disease, and 13 were alive (six disease free and seven with persistent disease). Survival probabilities of the sample were 79% at 6 weeks, 48% at 20 weeks, and 24% at 104 weeks. Univariate analyses revealed no significant difference in the survival times of medically versus surgically treated patients; age greater than 60 years at diagnosis of cancer, presence of ascites, low serum albumin levels, elevated blood urea nitrogen levels, elevated alkaline phosphatase levels, lack of previous radiotherapy (p less than 0.002 for all), advanced tumor stage, normal/ileus x-ray results, and a short diagnosis to obstruction interval (p less than 0.04 for all) resulted in lower survival probabilities. PMID- 3341402 TI - Presurgical prognostic factors in carcinoma of the cervix, stages IB and IIA. AB - Possible prognostic factors in early stage cervical cancer include patient age, tumor size, cell type, differentiation, and channel invasion. In this study each of these factors was evaluated based only on the findings available before surgery, and the observations are compared with patient survival and incidence of node metastases. One hundred consecutive patients with stage IB or IIA cervical cancer treated by primary radical surgery and followed at least 2 years are reported. Disease-free survival was 90% at 2 years and 85% at 5 years; 19% had node metastases. Of the factors studied, only age greater than 50 years was associated with poor prognosis (p less than 0.02 versus age less than 50 years). Only large tumor size was associated with increased node metastases (p less than 0.001 versus medium and small size). Tumor cell type, differentiation, and channel involvement had no bearing on survival or node metastases. Because older age and large tumors appear to be factors of poor prognosis for surgery, and yet it is not clear that these patients fare better with radiotherapy, we suggest a prospective trial of radiotherapy versus surgery for this group. PMID- 3341403 TI - Active management of labor and operative delivery in nulliparous women. AB - There has been a fourfold increase in cesarean births in Canada in the last 20 years. The two main indications are dystocia and repeat cesarean section. Of all primary cesarean sections, about half are due to dystocia. This is largely confined to nulliparous women. Work from Ireland suggests that a policy of active management of labor may reduce dystocia. This involves a uniform policy of amniotomy once a diagnosis of labor is established, followed by oxytocin augmentation if labor is nonprogressive (less than 1 cm/hr). From October 1, 1985, to December 31, 1986, this policy was carried out on 552 consecutive normal nulliparous women in spontaneous labor at greater than or equal to 37 weeks' gestation with a single fetus in vertex presentation with no fetal distress. These results were compared with a control group of 533 similar nulliparous women delivered between January 1, 1984 and March 31, 1985. The cesarean section rate dropped to 4.3% from 13% (p less than 0.005) and the forceps delivery rate dropped to 19.4% from 29% (p less than 0.005). The duration of labor greater than 12 hours dropped to 7% from 20% (p less than 0.005). There was no increase in fetal morbidity or mortality. PMID- 3341404 TI - Assessment of fetal risk in postdate pregnancies. AB - To assess postdate fetal risk, pregnancies in which menstrual history was confirmed by early ultrasound examination were reviewed; 5915 pregnancies within 1 week of term, 1408 1 to 2 weeks postdate, and 340 at least 2 weeks postdate. Fetal distress and meconium release were twice as frequent and meconium aspiration eight times as frequent postterm. Birth asphyxia was unrelated to gestational age. Fractures and palsies were more frequent because of primiparity and macrosomia. Only one antepartum fetal death occurred in 1748 postdate pregnancies. Review of 674 perinatal deaths at 37 plus weeks in Quebec showed no increase in deaths postterm. The increase in fetal distress and meconium aspiration postterm without an increase in birth asphyxia or fetal death may reflect greater responsiveness of the more mature fetus to mild asphyxic insults. Findings of this study could not justify increased fetal monitoring in postdate pregnancies. PMID- 3341405 TI - Fetal heart rate and activity patterns in growth-retarded fetuses: changes after vibratory acoustic stimulation. AB - Seventeen pregnant women who subsequently were delivered of infants with birth weights less than the third percentile were studied for examination of fetal heart rate and fetal activity patterns before and after a 5-second external vibratory acoustic stimulation. None of the fetuses was acidotic at birth. A reduced time was noted during which accelerations in heart rate occurred (50% less) and long-term fetal heart rate variability (25% less) in small for gestational age fetuses compared with age-matched, normally grown fetuses. The incidence of gross fetal body movements was significantly lower (40% less) in small for gestational age fetuses than in those who were appropriate for gestational age. Fetal heart rate and fetal activity patterns after stimulation with the electronic artificial larynx in small for gestational age fetuses were similar to those of appropriate for gestational age fetuses. PMID- 3341407 TI - Evaluation of fetal cardiac dysrhythmias with two-dimensional, M-mode, and pulsed Doppler ultrasonography. AB - Forty-three patients with fetal cardiac dysrhythmia were referred to a tertiary ultrasound department for further evaluation. The patients were subdivided according to the type of dysrhythmia diagnosed. All patients with irregular fetal heart rate had a good perinatal outcome. Of the six patients with fetal tachycardia, two required in utero therapy with maternal digoxin, and one of these fetuses had a cardiac tumor. The eleven patients with fetal bradycardia had the worst perinatal outcome, with four deaths occurring. The results suggest that all patients with fetal tachycardia or bradycardia should have a complete fetal cardiac assessment in a center experienced with the management of such cases. PMID- 3341406 TI - The significance and importance of prenatal diagnosis of fetal cardiac malformations by Doppler echocardiography. AB - Pulsed Doppler echocardiography is an excellent technique for cardiac diagnosis and assessment of cardiac performance in combination with M-mode and two dimensional echocardiography. Its exact role in fetal cardiac diagnosis has not been established. We examined 67 high-risk fetuses for cardiac malformations and found cardiac abnormalities or malfunction in 15. In four fetuses pulsed Doppler echocardiography played a primary or a definitive diagnostic role: One fetus had a complete atrioventricular canal, another lacked the pulmonary valve, the third had transposition of the great vessels without ventricular septal defect, and the fourth had high cardiac output failure caused by placental chorioangioma. Pulsed Doppler echocardiography is an integral part of the ultrasonic cardiac examination in high-risk fetuses and should be used in combination with two dimensional and M-mode echocardiography. It has an important place in the diagnosis of high-risk fetuses and may have a primary role in the diagnosis of fetuses when ultrasound resolution is poor, where cardiac circulatory hemodynamics are essential for diagnosis, and in complicated cardiac malformations in which a comprehensive and accurate diagnosis can be achieved only with pulsed Doppler echocardiography. PMID- 3341408 TI - Maternally perceived fetal activity from twenty-four weeks' gestation to term in normal and at risk pregnancies. AB - Maternal perception of fetal activity was studied in normal and at risk pregnancies from 24 weeks' gestation until term in the second and third hour after a maternal meal. The trend for the median number of maternally perceived fetal movements in the 2-hour observation period, across gestation, was similar to that previously reported in both maternally perceived and ultrasound studies. The median number of perceived fetal movements in any 15-minute interval was similar for both groups and was constant over gestational age. The periodicity of fetal activity perceived by mothers correlated well with ultrasonic observations. The data support that fetal movement counts are very variable. Periodicity must be taken into account when maternally perceived fetal activity is used as a screen of fetal well-being. The data suggest that the patient should be observed for a consecutive period, up to a maximum of 2 hours. If no fetal activity is perceived by 2 consecutive hours of observation, then further evaluation of fetal well-being should be considered. PMID- 3341410 TI - Invasive squamous cell carcinoma of the cervix in women less than 35 years old: recurrent versus nonrecurrent disease. AB - Invasive cervical squamous cell carcinoma was diagnosed in 45 patients less than 35 years old from 1980 to 1985. Thirty-two cases were Stage IB; 10, Stage IIB; and three, Stage IIIB. Twenty-two patients developed persistent or recurrent disease. Only one of these is now alive with no evidence of tumor. The mean interval from diagnosis to recurrence was 8.7 months (median of 7.0) and from diagnosis to death was 14.7 months (median of 12.0). Eleven of 32 patients with Stage IB disease developed a recurrence; the intervals to recurrence in Stage IB disease were similar to those for more advanced stages. Factors predicting recurrence included advanced stage of the disease and tumor bulk (maximum size, depth of invasion, and number of involved quadrants) as well as an exophytic or ulcerative tumor and a symptomatic presentation. These factors may identify the patient at high risk for recurrence who would benefit from adjuvant therapy. PMID- 3341409 TI - Prognostic significance of positive peritoneal cytology in endometrial carcinoma. AB - A retrospective review of 280 patients with endometrial carcinoma who had peritoneal cytologic examination done at the time of laparotomy was undertaken. A positive cytologic finding was the only manifestation of extrauterine disease in 16 patients (6%). Four (25%) of these patients had a recurrence. Only 13 (5%) of 237 patients with negative cytologic findings had a recurrence. Positive peritoneal cytology is a marker for potential recurrence. PMID- 3341411 TI - Gestational age and fetal biophysical assessment. AB - With improved neonatal care, biophysical assessment to detect fetal asphyxia is used increasingly at an earlier gestational age. We have tested five fetal biophysical variables: nonstress test, fetal breathing movements, fetal movements, fetal tone, and amniotic fluid volume 11,012 times in 5582 singleton fetuses in whom there was a normal perinatal outcome. The nonstress test and fetal breathing movements were more likely to be abnormal at 26 to 33 weeks' gestation compared with 34 to 41 weeks. The nonstress test, fetal breathing movements, fetal tone, and amniotic fluid volume were more likely to be abnormal at 42 to 44 weeks' gestation compared with 37 to 41 weeks. Fetal biophysical tests should be interpreted in relation to gestational age. PMID- 3341412 TI - Anticomplementary activity in serum of women with a history of recurrent pregnancy loss. AB - Viral complement fixation tests on women with a history of recurrent pregnancy loss were complicated by the presence of anticomplementary activity. This activity reflects the presence of a factor(s) in a patient's serum that nonspecifically fixes complement. When all patient sera tested were compared, 64.7% of women with recurrent pregnancy loss had anticomplementary activity compared with 22.0% among normal fertile pregnant women (p less than 0.01). In delineating when anticomplementary activity developed, it was found that 41.8% of women with recurrent pregnancy loss compared with 12.9% of normal pregnant women had this activity on entry to the study (p less than 0.01). This was primarily due to the fact that among women with recurrent pregnancy loss 50.0% of the pregnant versus 33.0% of the nonpregnant women had activity (NS). However, 55.2% of the anticomplementary negative women with recurrent pregnancy loss converted to a positive status compared with 15.4% of normal women (p less than 0.05). This was directly influenced by a conversion rate of 78.6% during pregnancy among women with recurrent pregnancy loss who entered the study nonpregnant and with no known cause for loss compared with a 33.3% conversion rate in their pregnant counterparts with recurrent pregnancy loss (p less than 0.025). Conversion to positive anticomplementary status occurred primarily by 20 weeks of gestation and appeared to be transient. Overall there was no association between the presence of anticomplementary activity and cervical colonization with genital mycoplasmas. The data suggest that women with a history of recurrent pregnancy loss develop a serum factor(s), usually by 20 weeks' gestation, that fixes complement. Thus these observations describe an additional anomaly in the immune system of women who experience recurrent pregnancy loss. PMID- 3341413 TI - A pharmacologic approach to the infusion of ritodrine. AB - The recommended regimen for the infusion of ritodrine leads to unnecessarily high plasma concentrations. A review of basic pharmacologic principles provides a basis for changing the infusion regimen. A regimen is proposed that results in lower average and peak concentrations and reduces the total amount of drug given. These changes may decrease the risk of developing side effects without adversely affecting the ability to inhibit preterm labor. PMID- 3341414 TI - The grandmultipara: is she still a risk? AB - Grandmultiparity is reported to increase both maternal and perinatal mortality and morbidity. Unique religious and demographic factors in Jerusalem allowed us to analyze a population wherein parity could be dissociated from socioeconomic status. A total of 7785 mothers was studied, 889 (11.5%) of whom were grandmultiparas. Comparison of grandmultiparous mothers with all others revealed no increase in the incidence of hypertension, diabetes, uterine atonia, antenatal or postnatal hemorrhage, cesarean sections, stillbirth rate, or congenital malformations. The grandmultipara had significantly lower neonatal mortality and low birth weight rates and a significantly higher incidence of multiple births and trisomy 21 (p less than 0.01). These results strongly suggest that grandmultiparity in and of itself in a healthy, economically stable population afforded modern medical care is not a major risk factor and that previous reports primarily reflected social class factors and not parity per se. PMID- 3341415 TI - The frequency of aneuploidy in prenatally diagnosed congenital heart disease: an indication for fetal karyotyping. AB - The frequency of chromosomal abnormalities in infants with congenital heart disease has been estimated from postnatal clinic data to be 5% to 10%. Over an 18 month period we performed fetal echocardiograms on 502 fetuses and found cardiac anomalies in 34. Eleven of these fetuses (32%) had abnormal chromosomes. This marked discrepancy from the data found in the pediatric literature may relate to nonviable fetuses identified in utero, who escape pediatric case identification. We conclude that in cases of fetal heart disease the workup should include either amniocentesis or fetal blood sampling for chromosome analysis. The information can be used for complete parental counseling and for managing delivery and neonatal care. PMID- 3341416 TI - Does maternal platelet-associated or platelet-bindable IgG correlate with levels in umbilical cord blood or colostrum during normal pregnancy? AB - Existing data regarding the ability to predict neonatal thrombocytopenia during maternal immune thrombocytopenia are confusing. We studied normal pregnancies (n = 20) to define normal values and the correlation between maternal and umbilical cord platelet counts, platelet-associated immunoglobulin G (IgG), and platelet bindable IgG. The postpartum serum platelet-bindable IgG level was measured to evaluate peripartum changes and the correlation with colostrum platelet-bindable IgG (n = 6). The mean maternal platelet count was 181,500 cells/cm3 mm and the mean umbilical cord platelet count was 293,500 cells/mm3. The median maternal platelet-associated IgG was 803 molecules per platelet, umbilical cord platelet associated IgG was 791 molecules per platelet, maternal platelet-bindable IgG was 92 molecules per platelet, and umbilical cord platelet-bindable IgG was 256 molecules per platelet. The postpartum median maternal platelet-bindable IgG was 333 molecules per platelet and for colostrum it was 297 molecules per platelet. No clinically useful correlations for predicting the neonatal platelet count during normal pregnancy were found. Normal pregnancies may have high levels of maternal- or umbilical cord platelet-associated IgG, perhaps due to nonspecific binding. PMID- 3341417 TI - Cold-induced abortion in paramyotonia congenita. AB - Paramyotonia congenita is a rare autosomal dominant disorder with complete penetrance. Its most typical clinical feature is the precipitation of active myotonia by exposure to cold. We report a case of cold-induced abortion in a woman with paramyotonia congenita. PMID- 3341418 TI - Heterotopic pregnancy: report of four cases. AB - Four patients with heterotopic (combined) pregnancies were treated at one institution during the period of a year. The use of fertility agents, infertility surgery, and pelvic inflammatory disease may be risk factors predisposing to an increasing incidence of such pregnancies. Combined pregnancy may reasonably belong in the differential diagnosis in certain clinical settings. PMID- 3341419 TI - Congenital limb reduction deformities and oral contraceptives. PMID- 3341420 TI - Dihydralazine and the uteroplacental blood flow. PMID- 3341421 TI - Anticardiolipin antibodies and habitual abortion. PMID- 3341422 TI - Recurrent partial mole. PMID- 3341423 TI - Parity and the contraceptive sponge. PMID- 3341424 TI - Influences of perinatal asphyxia on respiratory distress syndrome. PMID- 3341425 TI - Analysis of contaminants in discolored amniotic fluid. PMID- 3341426 TI - Evaluation of computerized axial tomography of eclamptic women with seizures refractory to magnesium therapy. PMID- 3341427 TI - Excimer laser keratectomy for correction of astigmatism. AB - We treated 13 eyes (12 patients) with excimer laser surgery for correction of astigmatism using linear corneal T-excisions. All eyes were followed up for a minimum of three months. We used a newly developed delivery system and special contact masks to deliver the 193-nm excimer light. Astigmatic corrections of up to 4.16 diopters were obtained. The actual corrections corresponded well with the intended values as predicted by a biomechanical theory. The refractive change over time was different than that observed after knife incisions, suggesting different repair mechanisms. An epithelial plug filling the whole T-excision persisted for over one year in all eyes. PMID- 3341428 TI - Sensorineural hearing loss in patients with typical retinitis pigmentosa. AB - We performed detailed audiologic testing in 45 patients with retinitis pigmentosa and 45 age- and sex-matched controls. Ten (22%) of the retinitis pigmentosa patients had a sensorineural hearing loss that varied from mild to severe. None of the control subjects had a hearing loss. Audiograms measured over a ten- to 30 year period were available for four patients with retinitis pigmentosa and each showed progressive hearing loss. The results indicate the important role of audiologic evaluation in treating patients with retinitis pigmentosa. PMID- 3341429 TI - The relation of rhodopsin and scotopic retinal sensitivity in sector retinitis pigmentosa. AB - We used reflection retinal densitometric, psychophysical, and electroretinographic techniques to study the scotopic retinal function of a mother and her three daughters who had clinical evidence of a sectoral type of retinitis pigmentosa. Retinal regions with, and those without, ophthalmoscopic signs of degeneration were investigated. During dark adaptation, the time courses of rhodopsin regeneration and recovery of scotopic sensitivity were similar to normal as was the relation of rhodopsin to scotopic threshold. In dark-adapted eyes, threshold increases were not proportional to rhodopsin loss. The results of psychophysical tests of background adaptation and temporal summation, and analysis of the relation of electroretinographic a- to b-wave amplitudes, led to the conclusion that abnormalities of photoreceptor cell function central to the rhodopsin-bearing outer segments accounted for the increased thresholds. PMID- 3341430 TI - Low-contrast letter charts to detect subtle optic [corrected] neuropathies. AB - We performed visual contrast sensitivity testing with Regan's low-contrast letter charts on 30 patients with optic neuropathies and good Snellen visual acuity. Results of this testing were compared with color vision and the presence of an afferent pupillary defect. Regan's low-contrast letter charts were found to be 93% sensitive for detecting subtle optic neuropathies, with the apparent false negative findings being readily explainable. Color vision testing was abnormal in only 49% of eyes with known optic neuropathies. PMID- 3341431 TI - Ganglioglioma of the optic nerve. AB - We examined a 15-year-old boy who had a ganglioglioma involving the left optic nerve, which caused proptosis, decreased vision, and optic atrophy. Computed tomography demonstrated an intraconal mass along the course of the orbital portion of the optic nerve. The only evidence of systemic neurofibromatosis was axillary freckling. The patient underwent a combined medial and lateral orbitotomy and excision of the tumor. Histologic examination demonstrated a mass composed of neurons and glial cells characteristic of ganglioglioma. After a one year follow-up period, we have found no evidence of recurrence. PMID- 3341433 TI - Nuclear sclerosis after vitrectomy for idiopathic epiretinal membranes. AB - We performed a retrospective analysis of lens changes occurring after vitrectomy for idiopathic epiretinal membranes causing macular pucker on 75 consecutive phakic eyes. Thirty-five eyes (47%) had appearance or progression of nuclear sclerosis. There were no changes in anterior subcapsular cataracts and three eyes (4%) had minimal changes in posterior subcapsular cataracts. Based on univariate analysis, presence of preoperative nuclear sclerosis, length of follow-up period, and surgeon were found to be associated with the occurrence or progression of nuclear sclerosis. Differences between surgeons were largely accounted for by the difference in proportions with preoperative nuclear sclerosis, and differing lengths of follow-up. Kaplan-Meier life table analysis performed on 53 eyes with examination of fellow eyes and longer follow-up showed significantly more nuclear sclerosis in the operated on eye when compared to the fellow eye (log-rank test, P less than .0001). PMID- 3341432 TI - Sustained reduction of intraocular pressure in humans with the calcium channel blocker verapamil. AB - We investigated the effect of the calcium channel blocker verapamil on intraocular pressure in human volunteers. In the initial trial, 15 subjects with untreated ocular hypertension were tested. After a baseline measurement was obtained with applanation tonometry, a 40-microliter drop of verapamil, 1.25 mg/ml, was instilled in one eye. After 30 minutes, a second reading was taken. In a subsequent trial of 12 untreated ocular hypertensive subjects, the duration of action was determined using the same dose and method of delivery. Results showed that verapamil elicited a mean +/- S.E.M. change in intraocular pressure of -3.8 +/- 0.900 mm Hg in the treated eye, and -1.6 +/- 0.400 mm Hg in the untreated eye. This reduction was statistically different in both eyes (treated eye, P = .0007; untreated eye, P = .005). This decrease in intraocular pressure remained statistically significant when compared to predrug baseline values for up to ten hours. PMID- 3341434 TI - Twin vessels in von Hippel-Lindau disease. AB - We examined ten patients from three families with von Hippel-Lindau disease and 26 of their at-risk relatives for the presence of twin vessels, defined as a paired retinal arteriole and venule that are separated by less than the diameter of one venule and extend for a distance of more than one disk diameter. They were compared with 36 age- and sex-matched controls. Of the 36 subjects in the study group, 23 had twin vessels compared with two controls (P less than 10(-6). Of the ten patients, nine (14 eyes) had twin vessels; no twin vessels were found in their controls (P = 5.9 x 10(-5)). Fourteen at-risk relatives and two of their controls had twin vessels (P = 9.4 x 10(-4)). PMID- 3341435 TI - Pathogenesis and therapy of traction detachment in various retinal vascular diseases. AB - We examined six patients with retinal vasculopathies (two cases each of angiomatosis retinae [von Hippel-Lindau disease], exudative vitreoretinopathy, and Coats' disease), who developed preretinal and vitreal membranes, retinal traction detachment, and exudation under the retina. The membranes consisted of a core of collagen of various diameter fibers usually covered on both sides by cells that displayed glial cell characteristics. The retina reattached spontaneously and exudates disappeared when traction was eliminated by vitreous surgery. Membrane formation did reoccur after vitrectomy if the vessels continued to leak, leading again to traction and subretinal exudation. Treatment consisted of surgical removal of vitreal and preretinal membranes and destruction of leaking vessels. PMID- 3341436 TI - HLA typing in birdshot chorioretinopathy. AB - We examined 49 patients with birdshot chorioretinopathy in whom HLA typing had been performed. Of these 49 patients, 47 (95.9%) had the HLA-A29 antigen. The HLA B12 (B44) antigen was also significantly associated with the disease, but this antigen is known to be in linkage disequilibrium with the antigen HLA-A29. The HLA-A2 antigen was less frequent in patients with birdshot chorioretinopathy than in the control group of normal European individuals (20% as compared to 44.6%). PMID- 3341438 TI - Pseudomonas corneal ulcer associated with colored cosmetic contact lenses in an emmetropic individual. PMID- 3341437 TI - Effects of gentamicin on healing of transdifferentiating conjunctival epithelium in rabbit eyes. AB - We examined the effects of commercially prepared gentamicin, a wide-spectrum topical antibiotic, on the healing of epithelial defects of the rabbit cornea. Abrasions were created by: (1) removing the corneal epithelium and 3 mm of the conjunctival epithelium (Group 1); and (2) producing the same initial trauma and subsequently removing the central 8 mm of epithelium 28 days after initial healing (Group 2). The complete healing of the large corneal and conjunctival epithelial defects was not delayed when gentamicin solution was used four times a day (Group 1). When the healed epithelium was reinjured while transdifferentiating from conjunctival to corneal epithelium (day 28, Group 2), treatment with the gentamicin solution and its vehicle, both containing benzalkonium chloride, delayed epithelial healing significantly compared with treatment with saline (P less than .01). PMID- 3341439 TI - Ischemic optic neuropathy in sickle cell disease. PMID- 3341440 TI - Immunosuppressive acidic protein in Behcet's disease. PMID- 3341441 TI - A simple extrusion needle with flexible cannula tip for vitreoretinal microsurgery. PMID- 3341442 TI - Full-frame angiography for the Zeiss fundus camera. PMID- 3341443 TI - Use of specular photomicrography with a new type of film. PMID- 3341444 TI - An analysis of the effect of intravitreal blood on visual acuity. PMID- 3341445 TI - Limbal- vs fornix-based conjunctival trabeculectomy flaps. PMID- 3341446 TI - Histopathologic and immunohistopathologic features of subretinal fibrosis and uveitis syndrome. PMID- 3341447 TI - Visual recovery in combined central retinal artery and central retinal vein occlusion. PMID- 3341448 TI - AIDS-related Kaposi's sarcoma displays differential expression of endothelial surface antigens. AB - The authors studied 11 cases of Kaposi's sarcoma (KS) in patients with the acquired immunodeficiency syndrome (AIDS) for their reactivity with two monoclonal antibodies (B721 and E431) that recognize endothelial cell surface antigens. Reactivity of these antibodies with KS was compared with the reactivity of other known endothelial markers (F8rAg, Ia, HCL-1). Staining was done with avidin-biotin-alkaline phosphatase immunohistochemistry on acetone-fixed frozen sections. In all samples of tumor both the spindle cell component and the vascular lining cells stained with both B721 and E431. In general, the spindle cells stained less intensely than did the vascular lining cells. There was both intratumor and intertumor variability. B721 and E431 are proposed as two additional markers for KS, and it is suggested that their reactivity with the tumor supports the hypothesis that KS is derived from vascular endothelium. The possibility is also raised that the variability of staining for vascular markers could have diagnostic possibilities, and further studies for investigation of this hypothesis are suggested. PMID- 3341450 TI - Immunocytochemical distribution of a breast carcinoma associated glycoprotein identified by monoclonal antibodies. AB - A glycoprotein, BCA-225 (Mr 225,000-250,000), has been identified in cells and spent medium of clone 11 T47D breast carcinoma cells by three murine monoclonal antibodies, CU18, CU26, and CU46. The antigen was localized in paraffin sections of 167/178 (94%) Bouin's-fixed human breast carcinoma tissues and few other carcinomas (1/8 lung [squamous], 4/4 uterine cervix) in an intracellular pattern, whereas an apical or glycocalyx distribution was seen in several normal tissues, benign lesions, and malignant tumors. Although the immunocytochemical staining patterns observed with these antibodies have many similarities to those described with other previously reported monoclonal antibodies, notable differences include the lack of reactivity of CU18, CU26, and CU46 with lactating mammary gland and with gastrointestinal malignancies. BCA-225 binds to wheat germ lectin, not to concanavalin A, but monoclonal antibody binding does not appear to involve the carbohydrate component of the molecule. The frequency of the immunocytochemical detection of BCA-225 in breast carcinomas and its restricted distribution in other human tissues suggest considerable clinical potential for this antigen and its corresponding monoclonal antibodies. PMID- 3341449 TI - Distribution of chromogranin A and secretogranin I (chromogranin B) in neuroendocrine cells and tumors. AB - The distribution of chromogranin A and secretogranin I (chromogranin B) in normal and neoplastic human endocrine tissues was analyzed with two human monoclonal antibodies against chromogranin A, anti-bovine antiserum against chromogranin A, and an anti-rat antiserum against secretogranin I. Western blotting analyses showed both chromogranin A and secretogranin I in normal adrenals, pheochromocytomas, a pituitary adenoma, and in normal pituitary glands, but not in a bladder carcinoma. Rat adrenal medullary and anterior pituitary tissues reacted with the polyclonal chromogranin A and secretogranin I antisera, but not with the two monoclonal chromogranin A antibodies. All antibodies reacted with most of the neuroendocrine cells and tumors examined. Pituitary prolactinomas contained immunoreactive secretogranin I, but not chromogranin A. Analysis of the distribution of chromogranin A and secretogranin I in pancreatic islet cells showed that chromogranin A was found predominantly in the glucagon-producing A cells, whereas secretogranin I was present in less than 5% of islet cells. These results indicate that chromogranin A and secretogranin I are both useful in the characterization of some neuroendocrine cells and neoplasms. PMID- 3341451 TI - Selective morphologic alterations of the cardiac conduction system in calves deficient in vitamin E and selenium. AB - Vitamin E and selenium (E-Se) deficiency causes necrosis of the contractile myocardium in many species but does not usually affect the cells of the conduction system. In the present study, experimental E-Se deficiency in cattle produced preferential degeneration and necrosis of Purkinje cardiocytes. Calves fed deficient diets for 127-137 days had sublethal damage characterized histologically by sarcoplasmic accumulation of lipopigment granules; ultrastructurally, these granules corresponded to cytolysosomes that had a heterogeneous ultrastructure. Alterations in necrotic cells included mitochondrial mineralization, sarcoplasmic condensation, and plasmalemmal fragmentation. Necrosis of Purkinje cells was followed by macrophagic penetration of the external lamina, phagocytosis of necrotic sarcoplasm, and repair by fibrosis. Furthermore, E-Se depletion of calves resulted in only minimal alterations in the contractile myocardium. In contrast, feeding supplements of polyunsaturated fatty acids to E-Se-deficient calves intensified the Purkinje cell damage but also resulted in widespread degeneration and necrosis of the contractile myocardium. Accumulation of lipopigment supports a pathogenetic role for lipoperoxidation in development of the cardiac lesions of E-Se deficiency. These lesions constitute a unique example of preferential damage to Purkinje cardiocytes. This model offers an attractive method of studying damage and repair to the cardiac conduction system. PMID- 3341452 TI - Relationship of alveolar epithelial injury and repair to the induction of pulmonary fibrosis. AB - Explants of mouse lung were cultured at various stages of injury after exposure to hyperoxia for determination of whether endothelial or epithelial injury alone could stimulate fibrosis in a blood-free environment. Mice were exposed to 95% O2 for periods up to 6 days. Then one lobe of lung was prepared for organ culture, and others were used for assessment of lung damage by morphologic studies and by the protein and cellular content of bronchoalveolar lavage (BAL) fluid. Explants cultured when the lung showed endothelial injury only were not different from air exposed controls. As alveolar damage, particularly to Type 1 epithelial cells, increased at 6 days, more protein was found by lavage; and after culture, overall DNA synthesis in explants was reduced. Autoradiography showed that epithelial cell proliferation was preferentially retarded while fibroblast growth became predominant. Collagen production was also significantly increased after 3 and 6 days of culture. In these explants there were few macrophages and no white blood cells or other blood components. Some mice, returned to air after hyperoxia, showed prompt epithelial repair, and cultures of these lungs were not different from controls. The results suggest that severe injury and retarded repair of the alveolar epithelium disturbs normal epithelial-fibroblast interactions and is sufficient to promote the fibrotic process. Less severe injury involving the endothelium only is not associated with fibrosis. PMID- 3341454 TI - Dermatoglyphic variation and weight and length at birth. AB - Relationships between dermatoglyphic variables, including finger ridge counts and finger, palmar, and plantar pattern intensities, and weight and length at birth, were tested in a sample of 184 boys and 202 girls from Warsaw schools. No convincing evidence for such relationships has been obtained from the results of correlations and one-way analysis of variance, although there are indications that some palmar traits may be related to length at birth in females. The data agree with the common belief that birth weight and birth length are mainly determined by influences operating in later stages of pregnancy, that is, after the 20th gestational week. PMID- 3341455 TI - Immunoglobulin (GM and KM) allotypes in the Sikh population of India. AB - The populations of India are genetically diverse, both within and between geographic regions; immunoglobulin (GM) allotypes provide important information on genetic differences between populations, since the frequencies of combinations of allotypes (termed "haplotypes") vary dramatically among ethnic groups. As part of a project to assess genetic diversity among defined Indian populations, we have examined eight GM allotypes in a sample of 101 unrelated Sikhs who have migrated to Toronto, Canada: Glm(1, 2, 3, 17) and G3m (5, 15, 16, 21). Sikhs are a religious group that arose in the Punjab about 1500 A.D.; most of the original converts are believed to have been middle to upper-middle caste Hindus. Gm allotyping showed that six Gm haplotypes occurred at polymorphic frequencies (greater than 0.01) in Sikhs: Gm3;5, Gm1,17;21, Gm1,2,17;21, Gm1,17;5, Gm1,17;15,16, and Gm1,3;5. These haplotypes have all been previously reported in Indian populations. The frequencies of the first four haplotypes resembled the published frequencies for lower-caste Hindus of NW India more than upper-caste Hindus. However, the last two haplotypes have been found only in upper-caste Hindus. The frequency of one of these, Gm1,17;15,16 was higher in Sikhs (0.09) than has been reported in any Indian population with the exception of Parsis (who are descended from Iranians). We speculate that the high frequency of this haplotype may have been characteristic of some of the Hindu castes in the Punjab from which Sikhs are descended. PMID- 3341456 TI - Morphological clues to genetic species: multivariate analysis of greater Galago sibling species. AB - Several studies conducted in diverse fields indicate the presence of a genetic discontinuity within the taxon Galago crassicaudatus E. Geoffroy--the thick tailed bushbaby. One of these areas is morphology. This contribution details a statistical analysis of skull material classified under this taxon in order 1) to confirm the objective existence of two morphotypes, and 2) to investigate the characters that allow the skull types to be distinguished. Emphasis is placed on multivariate techniques, although univariate and bivariate techniques are included where they are felt to be appropriate. All statistical analyses point to the reality of the morphological discontinuity between the groups. This is true even when size considerations have been reduced by rescaling the data. The results support separation of the populations at a specific level: G. crassicaudatus and G. garnettii. In addition, the structural changes observed in the two taxa--including an increase in overall size in G. crassicaudatus--are indicative of a divergence in preferred habitats: G. garnettii is adapted to more mesic environmental conditions, and to a softer, less fibrous diet than is its more robust sibling. PMID- 3341453 TI - Hepatocellular expression of a novel glycoprotein with sialylated difucosyl Lex activity in the active inflammatory lesions of chronic liver disease. AB - Hepatic expression of sialylated difucosyl Lex antigen (SDLex, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-) was studied with monoclonal antibody FH6, which defines this structure. Hepatocytes in the severe form of chronic active hepatitis and liver cirrhosis strongly expressed SDLex. The antigen was only weakly and focally detected in chronic persistent hepatitis. The mild form of chronic active hepatitis showed intermediate expression. SDLex expressed along the liver cell membranes displayed a honeycomb pattern when extensively expressed in the severe form of chronic active hepatitis or in liver cirrhosis. Cytoplasmic expression was faint and focal. Preferential tissue distribution was at the periphery of the hepatic lobules where the distruction of the limiting plate was present. The antigen was also expressed in sinusoidal lining cells and polymorphonuclear cells but not in the biliary epithelia. Hepatocytes expressing SDLex did not express related carbohydrate antigens, ie, Type 2 chain N-acetyllactosamine, Lex, and sialylated Lea. On subcellular fractionation, the microsome fraction contained the majority of the antigen activity. SDS-PAGE and Western blot analysis revealed one major SDLex-active glycoprotein with an apparent molecular weight of 110 kilodaltons. This glycoprotein was different from SDLex-active glycoproteins found in the sera of cancer patients. No ganglioside showed FH6 reactivity. These results indicate that liver cells in active inflammatory lesion expressed a novel glycoprotein carrying SDLex antigen in honeycomblike membrane-associated pattern. PMID- 3341457 TI - Effect of altitude on the lung function of high altitude residents of European ancestry. AB - The forced vital capacity (FVC), forced expiratory volume in one second (FEV), and ratio of FEV to FVC (%FEV) of 161 male and 158 female youths of European ancestry who were born at high altitudes and who were residing in La Paz, Bolivia (average altitude of 3,600 m) were examined and compared with those for lowland Europeans and highland Aymara Amerindians. FVC and FEV were significantly larger (p less than .001) in the La Paz Europeans than in two lowland control samples of European ancestry, with the relative differences between samples varying from small (1.5-4.1%) to moderate (7.7-11.9%). It could not be determined whether the enhanced lung volumes of the La Paz European children were acquired through an accelerated development of lung volumes relative to stature during adolescence, as is the case for Amerindian highlanders. After controlling for body and chest size, FVC and FEV were significantly smaller in the La Paz Europeans than in highland Aymara (p less than .001), suggesting that the lung volumes of the Aymara are influenced by factors other than simply growth and development at high altitude. Finally, as found in Amerindians, chest size is an important determinant of intra-individual variation in lung function among highland Europeans. PMID- 3341458 TI - A principal components analysis of human odontometrics. AB - It has long been recognized that tooth crown diameters in hominoids are all positively intercorrelated one with another. This study reports on sex-specific correlation matrices derived from 2,650 individuals from the Solomon Islands, Melanesia. Mesiodistal and buccolingual diameters of all permanent teeth from one side are used, excluding third molars. Analysis discloses significant sex dimorphism in the strengths of the intercorrelations, with females being better integrated. Principal components analysis (PCA) provides an objective means of data reduction (shown here to be preferable to simple size summation methods) and decorrelation of the resulting linear combinations. Four components are extracted (with results being virtually identical in the two sexes) and arguments are put forth that varimax rotation to "a simpler solution" may be counterproductive. Before rotation, the four components are 1) overall size, 2) buccolingual widths contrasted with mesiodistal lengths, 3) anterior (I,C) contrasted with posterior (P,M) teeth, and 4) premolars contrasted with molars. Most of the explained (shared) variance (63%) extracted by PCA is in overall size of the dentition. There is a strong urge to view the results of these principal components analyses as reflective of biologically and genetically meaningful entities. PMID- 3341459 TI - Abstracts of papers to be presented at the fifty-seventh annual meeting of the American Association of Physical Anthropologists. Kansas City, Missouri, March 24 26, 1988. PMID- 3341460 TI - Are psychiatric educators "losing the mind"? AB - Psychiatry is part of medicine, and developing competence to deal with the mental life of patients is an essential part of general medical as well as psychiatric subspecialty education. As psychiatry's neurobiological data base, therapeutic armamentarium, scope of interest, and philosophical views expand and competitive pressures for time in residency training are intensified, teaching in the mental sciences and opportunities for residents to develop solid psychodynamic diagnostic and therapeutic skills are rapidly disappearing. However, brain science does not yet, and probably never will, fully explain the mind. The author urges psychiatric educators not to give up the mind or, worse yet, lose it by default. PMID- 3341461 TI - Use of magnetic resonance imaging in psychiatry. AB - The authors report four cases in which magnetic resonance imaging (MRI) provided diagnostic information not apparent by X-ray CAT in clinical investigations of patients with neuropsychiatric disorders. The relative capabilities and contraindications for MRI and CAT are reviewed. The authors suggest that MRI is indicated 1) instead of CAT when there is suspicion of neuropathology that is better visualized by MRI because of its type or location and 2) after CAT when an atypical psychiatric symptom or presentation has not been definitively evaluated by means of CAT. PMID- 3341462 TI - Comparison of mania and depression after brain injury: causal factors. AB - Patients who developed secondary mania after brain injury (N = 17) had a significantly greater frequency of injury to right hemisphere areas connected with the limbic system than poststroke patients with major depression (N = 31), who had injury primarily in the left frontal cortex and basal ganglia. For patients without mood disturbance after brain injury (N = 28), the location of the lesion was not significant. Secondary mania patients also had a significantly greater frequency of family history of affective disorder than did the other two groups. These results suggest that an interaction between injury to certain areas of the right hemisphere and genetic factors or other neuropathological conditions produces secondary mania. PMID- 3341463 TI - Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients. AB - For 51 patients with rapid cycling affective disorder, clinical and family history data indicated that the illness was phenotypically and genetically related to more typical forms of affective disorder, was characterized by a bipolar course (100%), and was more common in women (92%). Manic-depressive cycles were separate from menstrual cycles. At the time of onset of rapid cycling, 73% of the patients were taking antidepressant drugs; the continuation of rapid cycling was associated with antidepressant drug therapy in 51% of the patients. Although most patients had been referred to a research ward because they were considered to be refractory to treatment, 37% attained essentially complete remissions, usually during treatment with lithium and/or monoamine oxidase inhibitors. PMID- 3341465 TI - Accuracy of the diagnoses of affective disorders and schizophrenia in public hospitals. AB - The authors compared hospital diagnoses with best-estimate research diagnoses of affective disorders and schizophrenia for patients admitted to public psychiatric hospitals in Maryland. The concern that there is overdiagnosis of schizophrenia and underdiagnosis of affective disorders was not supported by this study. PMID- 3341464 TI - Mental health, alcohol and drug use, and criminal history among homeless adults. AB - As part of a community-based survey of 529 homeless adults, the authors analyzed factors associated with their use of mental health services. Homeless persons who had had a previous psychiatric hospitalization were the least likely to sleep in an emergency shelter, had been homeless nearly twice as long as the rest of the sample, had the worst mental health status, used alcohol and drugs the most, and were the most involved in criminal activities. The majority had not made an outpatient mental health visit in 5 years. It is suggested that diverse systems of care are needed for homeless persons. PMID- 3341466 TI - Patients' suicides: frequency and impact on psychiatrists. AB - Results of a national survey of randomly selected psychiatrists revealed that 51% (N = 131) of the 259 respondents had had a patient who committed suicide. This event had an impact on both their personal and their professional lives. Sixty five psychiatrists reported stress levels in the weeks following the suicide that were comparable to levels reported in studies of people seeking treatment after the death of a parent. Younger, less-experienced clinicians were more affected by a patient's suicide than older clinicians with more experience. Implications of these results for the training and practice of psychiatrists are discussed. PMID- 3341467 TI - Electroretinograms in autism: a pilot study of b-wave amplitudes. AB - The authors recorded electroretinograms for 27 autistic patients and 20 age- and sex-matched healthy volunteers. Thirteen (48%) of the autistic patients demonstrated subnormal b-wave amplitudes, which may indicate abnormal retinal function. One patient was tested serially at two sites; his low b-wave amplitude did not vary over time or between the two sites. If this retinal finding can be confirmed at other laboratories and in larger samples of autistic patients, it might provide a marker for a specific subtype of autism. PMID- 3341468 TI - Depressions secondary to other psychiatric disorders and medical illnesses. AB - The authors studied 401 patients with depressions secondary to psychiatric illnesses (substance abuse disorders or somatoform, anxiety, or personality disorders) or depressions secondary to medical illnesses. They found that the patients with depressions secondary to psychiatric illnesses had an earlier age at onset, were more likely to have suicidal thoughts or to have made suicide attempts, were less likely to have memory problems, were less improved with treatment and more likely to relapse on follow-up, and had more alcoholism in their families than patients with depressions secondary to medical illnesses. Depressions secondary to medical illnesses seem to fit the category of reactive depression, and depressions secondary to psychiatric illnesses fit the definition of neurotic depression. PMID- 3341469 TI - Follow-up study of control subjects with lactate- and isoproterenol-induced panic attacks. AB - Eleven of 45 normal control subjects experienced panic attacks during lactate and/or isoproterenol infusions. Ten of the 11 subjects were followed up for a mean period of 32.5 months. Two subjects reported the development of spontaneous panic attacks during the follow-up period; one related the development of these attacks to the infusion experience. Neither subject met DSM-III criteria for panic disorder either before or after the infusions. Twenty-six healthy control subjects who did not experience panic attacks during the infusion experience did not report any attacks during a follow-up period of 31.1 months. PMID- 3341470 TI - The psychiatric uses of cold wet sheet packs. AB - The cold wet sheet pack is a treatment that is seldom discussed anymore. The authors present results of a national survey which demonstrated that this treatment is rarely used in modern American psychiatry. They retrospectively review its recent use for 46 hospitalized psychiatric patients and conclude that the treatment is safe and has interesting and useful effects that go beyond the concept of simple restraint. Further study of treatment with cold wet sheet packs is recommended before it disappears altogether. PMID- 3341471 TI - Methods of measuring thyroid hormone levels. PMID- 3341472 TI - The DST and suicide among depressed alcoholic patients. PMID- 3341473 TI - Death of a psychiatric patient from amantadine poisoning. PMID- 3341475 TI - AIDS education in U.S. psychiatric residency programs. PMID- 3341474 TI - Neuropsychological screening of severely disturbed psychiatric patients. PMID- 3341476 TI - Panic disorder and exercise. PMID- 3341477 TI - Carbamazepine-associated asterixis and hyperammonemia. PMID- 3341478 TI - Alcoholism, thyroid disorders, and left-handedness. PMID- 3341480 TI - More on haircutting and psychosis. PMID- 3341479 TI - Mania-like episodes associated with ranitidine. PMID- 3341481 TI - Suicide and mortality from diabetes. PMID- 3341482 TI - Neuroscience in the future of psychiatry. PMID- 3341483 TI - Prediction of dangerousness. PMID- 3341484 TI - Screening for child-molesting behavior. PMID- 3341485 TI - Origin and treatment of hallucinations. PMID- 3341486 TI - Seizure disorder or panic disorder? PMID- 3341487 TI - Avoidant, schizoid, and dependent personality disorders. PMID- 3341488 TI - Pathological crying and laughter. PMID- 3341489 TI - Premenstrual syndrome, hypothyroidism, and magnesium. PMID- 3341490 TI - Substance abuse category in DSM-III-R. PMID- 3341491 TI - Fear of having contracted AIDS. PMID- 3341492 TI - The right to health care--gains and gaps. PMID- 3341493 TI - Spermicide use and pregnancy outcome. AB - The relation between periconceptional vaginal spermicide use and sex ratio at birth, birthweight, and the frequency of congenital anomalies was examined in a cohort of 2,712 New York City obstetric patients, 149 of whom (5.5 per cent) became pregnant while using spermicides or had used spermicides before and after conception. Periconceptional spermicide use was not associated with any important variation in the expected sex ratio at birth, nor with major or minor congenital anomalies. Exposure to spermicides in the periconceptional period, defined dichotomously as present or absent, was not associated with decreased birthweight in male or female infants. There was a slight decrease in birthweight among female infants with increasing duration of postconceptional spermicide use; an estimated 7.4 grams decrease with each day of use. The size of the effect and its selectivity by sex suggest a chance finding. PMID- 3341494 TI - A comparison of women in and out of a prematurity prevention project in a North Carolina perinatal care region. AB - We assessed a prematurity prevention project in a North Carolina region with 21,000 annual births in terms of its impact on low birthweight. Project records were matched to birth certificates in order to compare characteristics of women in and out of the program who received prenatal care from private providers. A logistic regression analysis, in which the effects of race, marital status, age, and other risk factors for low birthweight were statistically controlled, showed that women not in the project were 1.32 times (95% Confidence Interval 1.14, 1.54) as likely as project participants to have a birth under 2500 grams. The relative risk for non-participants for a birth under 1500 grams was 1.87 (95% CI 1.25, 2.80). Strengths and limitations of the study are discussed. The results are consistent with previous work examining the etiologies of low birthweight in private versus public patients. PMID- 3341495 TI - Maternal smoking and low birthweight in the reproductive history of women in Puerto Rico, 1982. AB - In 1982, a representative sample of 3,175 women ages 15 to 49 years living in Puerto Rico were interviewed and complete reproductive histories obtained. Births to mothers who started smoking regularly at some time before delivery and who were still smoking at the time of the interview (the exposure definition) were compared with unexposed births. Our analysis of 4,444 single, live births delivered in public and private hospitals from 1946 through 1982 demonstrates that births to smoking women aged 20 and older delivering in public hospitals were 2.5 times more likely to weigh less than 2,500 grams (95% confidence interval (CI) = 1.9, 2.3), and on the average weighed 207 grams less (95% CI = 130, 284) than births to a comparable group of nonsmoking mothers. However, we found no other difference in birthweight between newborns of smoking and nonsmoking women when comparing their births within the same hospital category and age group. The data in this study suggest that the effect of smoking on birthweight among births to Puerto Rican women may be modified by maternal age and by whether the infant was born in a private or public hospital. PMID- 3341496 TI - Do regional variations in prevalence of cryptosporidiosis occur? The central Ohio experience. AB - We screened 2,780 consecutive stool specimens submitted for routine ova and parasite examination to assess the prevalence of cryptosporidiosis in a pediatric patient population in central Ohio. The stools were prepared by formalin-ethyl acetate concentration followed by cold Kinyoun acid-fast stain of the sediment. In addition, 912 consecutive intestinal biopsies were monitored for the presence of the parasite. Cryptosporidium oocysts were found in only 0.3 per cent of stool specimens (seven specimens from three patients) and in none of the intestinal biopsies. Due to this low prevalence of cryptosporidiosis, we conclude that routine screening of stool specimens for Cryptosporidium sp. is unnecessary in our patient population. Screening should be targeted to immune compromised patients and patients with persistent diarrhea and no apparent etiology. Our study also supports the concept that there are geographic variations in the prevalence of cryptosporidiosis. PMID- 3341497 TI - The rising long-term trend in occupational injury rates. AB - Establishment survey data for the United States as a whole and workers' compensation data for the State of California were used to document long-term trends in occupational injury and acute illness rates. After declining throughout the first half of the century, national rates of disabling injuries in manufacturing, construction, and the trade sector have risen sharply in recent decades. Injury rates in mining show no strong trend either up or down since 1960. Increases over recent years have been especially pronounced for strains and sprains, cuts, lacerations and punctures, bone fractures, and acute illnesses. Injury rates in the manufacturing sector are strongly influenced by general economic conditions--rising sharply with business upsurges and declining during recessions. Increases in the rate of unemployment, which decrease worker and labor union bargaining power, are associated with increases in injury rates within manufacturing. PMID- 3341498 TI - Food choices and the cancer guidelines. AB - Twenty-four hour dietary recall data from 11,658 adult respondents in the second National Health and Nutrition Examination Survey (NHANES II) (1976-80) were used to examine the American diet in relation to certain of the cancer dietary guidelines from the National Academy of Sciences and the American Cancer Society. The per cent who reported consuming any food in those food groups considered protective was small: cruciferous vegetables (18 per cent); fruits and vegetables high in vitamin A (21 per cent); high fiber breads and cereals (16 per cent). The per cent consuming foods potentially increasing cancer risk was high: red meat (55 per cent); bacon and lunch meats (43 per cent). Proportions of persons eating fruits and vegetables increased with income. Diets were closer to the guidelines for females than males, for Blacks than Whites, and for older than younger Americans. PMID- 3341499 TI - Usefulness of comprehensive feasibility studies in environmental epidemiology investigations: a case study in Minnesota. AB - Episodes of public water supply contamination with industrial or agricultural chemicals frequently give rise to public concerns about adverse health effects. These concerns may precipitate epidemiologic or clinical investigations requiring large expenditures of state and federal resources regardless of whether such investigations are justified by scientific criteria. An alternative is a comprehensive feasibility study, utilizing all available information to determine whether large-scale studies are warranted or feasible. At a relatively modest cost, a feasibility study allows health officials to identify information needs and deficiencies, outline potential study options and costs, clearly establish the rationale for a proposed study or, conversely, prevent unwarranted expenditures of public resources. Furthermore, a feasibility study may in itself resolve many community and scientific concerns. This article provides a case study of the usefulness of a formal feasibility study in a situation involving an elevated cancer rate and contaminated municipal water supply wells surrounding a federal superfund site. PMID- 3341500 TI - Vaccination against poliomyelitis: present possibilities and future prospects. PMID- 3341501 TI - The status of cancer cluster investigations undertaken by state health departments. AB - A survey of state health departments indicates the number of cancer cluster reports received is associated with the size of the state, the presence of a population-based tumor registry, and the existence of a centralized system for response. Cancer cluster investigations, have generally been unproductive in terms of etiologic discoveries yet they may have important benefits in terms of public education, allaying public anxiety about environmental concerns and engendering good will toward government agencies. PMID- 3341502 TI - Hepatitis B screening in a New York City obstetrics service. AB - A cross-sectional chart review study was performed of hepatitis B virus (HBV) surface antigen screening of 532 women admitted to a New York City hospital obstetrics service from 1984 to 1985. Comparison of serologic results to risk factors for hepatitis B revealed that women born outside the United States and those with a positive test for or history of a sexually transmitted disease were more likely to be infected with HBV. Obstetric clinics with large immigrant populations should consider screening all patients for HBV. PMID- 3341503 TI - Day care center illness: policy and practice in North Carolina. AB - We surveyed 62 North Carolina day care centers (DCCs) to determine their policies for excluding children. We found that the addition of a temperature of 100-101 degrees F to each of eight symptoms was associated with an increase in the percentage of DCCs choosing "immediate pick-up." Non-profit centers were more likely to send children home (70 per cent) than for-profit centers (48 per cent). Centers with and without written illness policies did not differ in their management of sick children. PMID- 3341504 TI - Pathogenic micro-organisms and helminths in sewage products, Arabian Gulf, country of Bahrain. AB - Fecal and sludge samples from the Arabian Gulf country of Bahrain contained poliomyelitis and coxackie viruses, coliform bacteria, Escherichia coli, Salmonella spp., Shigella sonni, fecal streptococci, Balantidium coli, Ascaris lumbricoides and Hymenolepis nana eggs, and Strongyloides stercoralis. Sludge produced in the central sewage treatment plant is used for agricultural purposes and poses a threat to public health. Recommendations to reduce the potential health hazards are made. PMID- 3341505 TI - Investigation of possible health effects of community exposure to fermenting wood chips. AB - We conducted a case-control study of emergency room (ER) patients to evaluate whether asthma is caused by living near a wood-chip fueled power plant that released wood-chip fermentation products. Only eight (29 per cent) of 28 asthma patients seen in the ER during an 11-week period lived within 1.5 miles of the plant compared with 18 (34 per cent) of 54 control patients matched for severity of diagnosis and seen during the same period (Mantel-Haenszel odds ratio controlling for age = 0.96). PMID- 3341506 TI - Sexual activity among US women of reproductive age. PMID- 3341507 TI - Beware of snowy roofs! PMID- 3341508 TI - Discontinuation of Bendectin. PMID- 3341509 TI - Is the Florida safety belt law effective? PMID- 3341511 TI - Papillary cystadenoma of the mesosalpinx in von Hippel-Lindau disease. AB - Papillary cystadenoma of the epididymis is an occasional finding in men with von Hippel-Lindau disease. To date, an analogous lesion has not been described in women with the syndrome. We report a case of an asymptomatic papillary cystadenoma of the mesosalpinx found incidentally during surgery for a renal cell carcinoma in a woman with von Hippel-Lindau disease. This finding supports the notion that similar lesions may arise in both men and women with von Hippel Lindau disease, perhaps from embryologically related portions of the urogenital tract. PMID- 3341510 TI - Mammary duct ectasia and pituitary adenomas. AB - Mammary duct ectasia developed in three postmenopausal patients who had had pituitary chromophobe adenomas. The first patient had bilateral duct ectasia that developed 8 and 11 years after hypophysectomy. The second patient, who also had bilateral ectasia, had a prolactin-producing pituitary adenoma for which bromocriptine was prescribed. The ectasia developed in one breast before commencing bromocriptine therapy, and in the other breast 2 years later. The third patient also had a prolactin-producing pituitary adenoma. Unilateral duct ectasia developed while bromocriptine was taken. The ectasia in all patients was very marked and affected all excised ducts. Cholesterol granulomas were sometimes very extensive. These cases suggest a relationship between certain hypothalamic/pituitary disorders, possibly related to prolactin secretion and the development of mammary duct ectasia in postmenopausal patients. PMID- 3341512 TI - Secretory breast carcinoma in a man. AB - A 23-year-old man who presented clinically with unilateral gynecomastia was found to have secretory breast carcinoma. The patient is free of disease 4 years following a modified radical mastectomy. The indolent biological potential of this rare variant of primary mammary carcinoma is evidenced by the long clinical history of a breast mass in this patient and the absence of axillary lymph node metastases. Although secretory carcinoma occurs both in children and adults, most examples have been reported in female patients. PMID- 3341513 TI - Mesothelioma vs. adenocarcinoma. PMID- 3341514 TI - Spermatocytic seminoma of testis with sarcomatous transformation. A report of five cases. AB - Five cases of spermatocytic seminoma of the testis associated with a sarcomatous component, one of them of rhabdomyosarcomatous type, are presented. No recognizable teratomatous structures were identified in any of the cases. The presence of the sarcomatous elements transformed the usually innocuous spermatocytic seminoma into a highly aggressive neoplasm, which led to the patients' death in at least two cases. The sarcomatous elements may represent a nonseminomatous germ cell component, but we prefer to view them as an expression of anaplastic transformation of the tumors, analogous to that seen in tumors in other organs. PMID- 3341515 TI - Dysplasia of nonmetaplastic gastric mucosa. A proposal for its classification and its possible relationship to diffuse-type gastric carcinoma. AB - In a review of 192 gastric resections, histological changes believed to represent dysplasia of nonmetaplastic gastric epithelium were observed. This paper presents a proposal for their classification. The main feature of this dysplasia is replacement of the differentiated cells lining the glands by undifferentiated cells with varying degrees of cytological abnormalities and cellular pleomorphism, but with absence of architectural glandular derangement. The classification is justified by cytokinetic and histologic observations in experimental gastric carcinogenesis and early human gastric carcinoma. The severity of the changes is graded, first, by the extent of involvement of the gland (crypt) as measured from the proliferative zone (PZ), and, second, by the degree of cytological abnormality. It utilizes a modification of the terminology of Riddell et al. (45) for dysplasia in inflammatory bowel disease wherein the term "dysplasia" denotes intraepithelial neoplasia. The changes are classified into (a) negative for dysplasia, (b) atypical, i.e., indefinite for dysplasia, and (c) positive for dysplasia. Changes negative for dysplasia are considered regenerative and consist of enlargement and vesicular transformation of the nucleus in the cells of the PZ and adjacent part of the crypt. Atypical changes consist of equivocal lesions difficult to classify as definitely regenerative or definitely dysplastic, and are hence called indefinite for dysplasia. They consist of loss of cytoplasmic differentiation of the cells lining the glands (i.e., mucus production and parietal and chief cell differentiation) with increased nuclear-cytoplasmic ratio and moderate cytological atypicality. Based on the extent of gland involvement, the group with atypical mucosa is subdivided into two categories--atypical, probably negative for dysplasia (AtN) and atypical, probably positive for dysplasia (AtP). Mucosa exhibiting unequivocal cytological features of neoplasia with cellular and nuclear pleomorphism is classified as positive for dysplasia (D). This is subdivided into low-grade and high-grade dysplasia, the latter representing carcinoma in situ. Glandular architecture remains undisturbed in all stages and the cells remain cuboidal, without transformation into intestinal-type cells. This type of dysplasia was found in a significantly higher number of diffuse-type carcinomas than in intestinal-type carcinomas. The previously well-recognized adenomatous or metaplastic dysplasia was significantly more prevalent in intestinal-type carcinoma than in diffuse-type.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3341516 TI - Ocular angiostrongyliasis in Japan: a case report. AB - A small motile worm was found in the posterior pole of the eye of a patient, producing a decrease in visual acuity. The patient had signs of meningitis and had cerebrospinal fluid eosinophilia. His serum was positive for antibodies to Angiostrongylus cantonensis. Without surgical intervention, the patient recovered and his visual acuity returned to normal. PMID- 3341517 TI - Biting activity of black flies in Guatemala: parity rates and differences between localities and habitats. AB - Host-seeking activity of anthropophilic black flies at 4 localities in Guatemala with different prevalence rates of onchocerciasis was assessed using human attractants and semimonthly catches over one year. Density of host-seeking Simulium ochraceum was greatest at the locality with the highest incidence of onchocerciasis and very reduced at the 2 localities with low levels of human infection. The overall percentage of parous host-seeking S. ochraceum at the 4 localities ranged from 41%-49%. Host-seeking activity appeared to be concentrated near streams containing immature stages, and few females dispersed as far as 3 km away. S. metallicum was the second most frequently captured species; however, at the locality with the highest prevalence of onchocerciasis, its host-seeking density was much less than that of S. ochraceum. For S. metallicum, the overall percentage of parous females ranged from 28%-34% at the 4 localities. S. metallicum were consistently taken in much greater numbers in coffee cultivation areas than in housing areas. Host-seeking S. callidum and S. gonzalezi also were captured. PMID- 3341518 TI - Seasonality of adult black flies and Onchocerca volvulus transmission in Guatemala. AB - Transmission of Onchocerca volvulus, principally by Simulium ochraceum, was studied over a 14-month period in the Atitlan region of Guatemala. Semimonthly catches of black flies were made on human volunteers at 4 localities with different prevalences of human onchocerciasis. Host-seeking activity of S. ochraceum reached its greatest magnitude in the early dry season (October January) but then declined rapidly and was lowest during the late dry season (February-May). The frequency of O. volvulus larvae in parous host-seeking S. ochraceum also varied seasonally, and this variation was most pronounced for third stage larvae. At a hyperendemic locality, the highest frequency of this larval stage occurred during the February-March period (0.0142 in 1979 and 0.0095 in 1980). From June-January, the frequency of third stage larvae in S. ochraceum was less than 0.003. The frequency of early first stage larvae exhibited the least seasonal variation, ranging from 0.0354 in August-September to 0.0628 in April-May. The transmission rate of O. volvulus by S. ochraceum also varied seasonally. At the same hyperendemic locality, infective biting density of S. ochraceum attained its greatest magnitude in February-March. The survival rate of female S. ochraceum from one gonotrophic cycle to the next was estimated from the ratio of flies with early first stage larvae to those with infective stage larvae. These rates varied seasonally and ranged from 0.2132 to 0.3974, with the highest rates occurring in the late dry season. PMID- 3341519 TI - A prospective study of dengue infections in Bangkok. AB - Dengue infections were prospectively studied among 4- to 16-year-old students at a Bangkok school. Blood samples were obtained from 1,757 students in June 1980, before the dengue season, and in January 1981, after the season, and tested for dengue antibodies by the hemagglutination inhibition method. Classrooms were monitored daily for school absences. Fifty percent of the children had antibodies to, and were presumably immune to, at least 1 dengue serotype by the age of 7 years. Most (90/103, 87%) students who became infected by dengue viruses during the study period were either asymptomatic or minimally symptomatic (absent only 1 day). Most (7/13, 53%) of the symptomatic dengue infections (absent with fever for greater than or equal to 2 days) were clinically recognized as cases of dengue hemorrhagic fever which required hospitalization. None of 47 primary dengue infections required hospitalization, whereas 7 of 56 secondary infections did (P = 0.012). Preexistent dengue immunity, as detected by conventional serologic techniques, was a significant (odds ratio greater than or equal to 6.5) risk factor for development of dengue hemorrhagic fever. PMID- 3341520 TI - Genetic variation of Venezuelan equine encephalitis virus strains of the ID variety in Colombia. AB - To determine the degree of genetic variation within one serologic group of Venezuelan equine encephalitis virus and the relatedness of viruses with different epidemiologic backgrounds isolated within the same country, virion RNA from 16 isolates belonging to subtype I were compared by RNase T1 oligonucleotide fingerprinting. RNA fingerprints of 12 enzootic isolates showed a large degree of heterogeneity, even though they were serologically indistinguishable. A reference enzootic strain from Colombia showed more genetic relatedness to three epizootic strains isolated in the same country, than to its own serogroup prototype strain isolated in Panama. Thus, genetic relatedness within Venezuelan equine encephalitis strains in Colombia seems to be a function of geography rather than epidemiology. PMID- 3341521 TI - Identification of isomorphic malaria vectors using a DNA probe. AB - About 7,000 recombinant clones, derived from chromosomally-identified families of wild-caught females of Anopheles dirus species D, were screened. The most promising clone was totally specific to species D when tested against single F1 females of all four species of the complex. In fresh specimens the clone was positive for DNA levels 150 times less than the normal DNA content of single individuals. Fresh adult males and females, larvae, and dried specimens have been successfully identified. The clone was sequenced; it is 124 bp long and appears to be repeated in the genome about 1.8 x 10(4) times. PMID- 3341522 TI - Cutaneous leishmaniasis in Guatemala: isoenzyme characterization of isolates from humans. AB - Leishmania organisms cultivated from cutaneous lesions of humans in Guatemala were characterized by cellulose acetate electrophoresis. Six isolates had electrophoretic enzyme patterns identical to World Health Organization reference strains of Leishmania braziliensis braziliensis, and 5 had patterns identical to reference strains of Leishmania mexicana mexicana. PMID- 3341523 TI - Isoenzyme electrophoresis of 30 isolates of Giardia from humans and felines. AB - Thirty isolates of Giardia duodenalis from humans and felines were compared by isoenzyme electrophoresis. Using 10 enzyme systems, 13 different zymodemes were distinguished. The majority of zymodemes could be divided into two groups: one group comprising human and feline isolates with worldwide geographic distribution; the other group containing human isolates restricted to Western Australia. A number of isolates showed multiple-banded patterns and the genetic significance of these findings is discussed. The marked heterogeneity of G. duodenalis demonstrated in this study is considered in relation to the epidemiology of giardiasis. The findings are consistent with felines serving as a reservoir of infection to humans. PMID- 3341524 TI - Pancreatitis and the biliary tree: the continuing problem. AB - Gallstone-associated pancreatitis continues to have a mortality rate that approaches 10 percent. In a review of 132 fatal cases of acute pancreatitis, no less than a third of the gallstone-associated cases were diagnosed for the first time at autopsy. Early diagnosis of gallstones in these patients remains problematic, but clinical and biochemical factors may aid ultrasonography in defining patients who require endoscopic retrograde cholangiopancreatography. Early operation is advisable in patients with mild disease, but endoscopic papillotomy should be considered in those with severe disease who fail to stabilize after admission. Chronic pancreatitis is frequently associated with cholangiographic evidence of biliary obstruction, and serum alkaline phosphatase concentrations offer a valuable means of monitoring cholestasis. If operation is needed to deal with biliary obstruction, the options are to carry out Roux-Y hepaticojejunostomy or resection of the pancreatic head, the choice being dictated by the indications for direct pancreatic operation. PMID- 3341525 TI - The lower esophageal sphincter in health and disease. AB - The ability of the lower esophageal sphincter to protect the esophageal mucosa from exposure to gastric juice depends on its resting pressure, length exposed to abdominal pressure, and overall length. Mechanical incompetency of the sphincter can occur when one or more of these components fail. The purpose of this study was to measure manometrically the normal percentile values for these components, and to identify the point differentiating a mechanically competent from an incompetent sphincter. The results show that a mechanically incompetent sphincter can be identified by a sphincter pressure below the 2.5 percentile, an abdominal length below the fifth percentile, and an overall length below the 2.5 percentile of normal values. Sixty percent of the patients with documented increased esophageal exposure to acid gastric juice had a mechanically incompetent sphincter. PMID- 3341526 TI - Increased biliary calcium in cholesterol gallstone formation. AB - The hypothesis that biliary calcium levels increase during cholesterol gallstone formation was tested in a prairie dog gallstone model. In addition to the previously documented changes in biliary lipid composition, animals with gallstones had a significant increase in gallbladder bile concentrations of total and ionized calcium compared with control animals. The observation that hepatic bile levels of calcium remained unchanged in the cholesterol-fed animals suggests that the increase in gallbladder bile calcium is due to a gallbladder-related phenomenon, rather than an alteration in hepatic metabolism. We proposed that this increase in biliary calcium levels results from an increase in gallbladder absorption. Increased biliary calcium levels may be an important, previously unrecognized, factor in the pathogenesis of cholesterol gallstones. PMID- 3341528 TI - Relationship between gallbladder contraction and progesterone receptors in patients with gallstones. AB - Stasis of bile within the gallbladder has long been suspected of having an important role in the pathogenesis of gallstone disease. We postulated that the female preponderance of gallstone disease might partly be related to the effects of progesterone, a known smooth muscle relaxant, on specific receptors in the gallbladder wall, leading to stasis of bile. A total of 42 patients with gallstone disease and 28 control subjects underwent radionuclide scan imaging and their gallbladder ejection fractions were calculated in response to intravenous infusion of cholecystokinin octapeptide. Patients then underwent cholecystectomy and a piece of gallbladder fundus was assayed for the presence of progesterone receptors. Receptors were present in 60 percent of patients. As a group, gallstone patients had a decreased ejection fraction compared with control subjects. The presence of progesterone receptors in the gallbladder wall was associated with a decreased percentage of ejection compared with both healthy control subjects and patients whose gallbladders were receptor-negative. We conclude that progesterone receptors are present in the gallbladder wall of gallstone patients and that their presence correlates with impaired gallbladder emptying. PMID- 3341527 TI - Predictors of total and low-density lipoprotein cholesterol change after partial ileal bypass. AB - POSCH is a prospective, randomized secondary intervention trial examining the effect of maximal lipoprotein modification achieved by partial ileal bypass on overall mortality and the course of coronary heart disease. In the initial 189 surgical patients, total cholesterol levels decreased from 256.7 +/- 2.6 mg/dl to 166.6 +/- 2 mg/dl, and low-density lipoprotein cholesterol levels decreased from 181.5 +/- 2.7 mg/dl to 94.1 +/- 1.7 mg/dl 3 months after operation. These significant decreases were sustained through 5 years of follow-up (p less than 0.001). The total cholesterol level was 29.2 +/- 0.9 percent lower and the low density lipoprotein cholesterol level was 43.2 +/- 1 percent lower at 5 years compared with the baseline level. Decreases of similar magnitude were seen in each of the common WHO lipoprotein phenotypes. The baseline total cholesterol level was the only significant independent preoperative predictor of the 5 year total cholesterol level (correlation coefficient 0.547; p less than 0.001), and the baseline low-density lipoprotein cholesterol level was the only significant independent preoperative determinant of the 5 year low-density lipoprotein cholesterol level (correlation coefficient 0.599; p less than 0.001). These relationships are expressed by the following equations: 5 year total cholesterol = 0.54 X baseline total cholesterol + 42.3, and 5 year low-density lipoprotein cholesterol = 0.455 X baseline low-density lipoprotein cholesterol + 19.2. The decrease in total and low-density lipoprotein cholesterol levels after partial ileal bypass are greater than reported by any trial of drug or diet intervention, including the Lipid Research Clinics Coronary Primary Prevention Trial which examined cholestyramine. Estimation of the change in total and low-density lipoprotein cholesterol levels after partial ileal bypass can be made based on preoperative lipid analysis and is essential in comparing different therapeutic modalities and assessing the role of partial ileal bypass among strategies aimed at lowering coronary heart disease risk. PMID- 3341529 TI - Influence of portal hemodynamics on long-term survival of alcoholic cirrhotic patients after small-diameter portacaval H grafts. AB - Estimating postoperative survival rates after portasystemic shunt procedures has concerned surgeons during the last 40 years. The relationship between survival and Child's classification has clearly demonstrated the importance of preoperative hepatic functional reserve. Maintaining hepatic portal perfusion has been proposed as an additional protective factor but has never been proved clinically. Our analysis of survival after partial shunting with small-diameter portacaval H grafts has shown that both hepatic functional reserve and postoperative portal perfusion correlate with postoperative survival in alcoholic patients, but the latter was a stronger correlate of long-term survival. A predictive model based on both factors has been described for estimating the overall survival rate of alcoholics after partial shunting with small-diameter portacaval H grafts. PMID- 3341530 TI - Controversies in the management of pancreatic pseudocysts. AB - Review of the diagnosis and treatment of patients with pancreatic pseudocysts over the past 8 years has led us to three conclusions regarding controversial aspects of their treatment. We found that patients who present with chronic pseudocysts can be identified with the help of computerized axial tomography and promptly undergo successful internal drainage, whereas patients with acute peripancreatic fluid secondary to pancreatitis can be observed expectantly with a 43 percent frequency of spontaneous resolution. Patients with infected pancreatic pseudocysts can be safely drained internally. The most common cause of extrahepatic biliary obstruction in this group of patients with pancreatic pseudocysts was stricture due to pancreatitis and fibrosis, not extrinsic compression. PMID- 3341531 TI - Influence of splenectomy on survival rate of patients with colorectal cancer. AB - Between 1966 and 1980, 68 patients were identified who had a splenectomy before or concurrent with resection of a colorectal adenocarcinoma. Control subjects with concurrent disease were then matched with each study patient for age, sex, stage of disease, and date of operation. Follow-up was complete. Between splenectomy patients and control subjects, there was no difference in the site of primary disease (rectum versus colon), the number of patients receiving adjuvant therapy, the technique of resection (cure versus palliation), or the extent of regional disease. Overwhelming sepsis occurred in only one splenectomy patient. Splenectomy was associated with a significant decrease in survival at 5 years in patients with regional (stage C) disease but not in patients with localized (stage B) disease. More splenectomy patients received blood transfusions than control subjects, but an independent effect on survival could not be demonstrated. The mechanism responsible for this adverse impact of splenectomy is undefined. However, splenectomy should be considered a possible factor in the survival of patients operated on for regional colorectal cancer. PMID- 3341532 TI - Effects of platelet-activating factor on canine gastric mucosal blood flow and permeability to luminal acid. AB - Recent studies suggest that platelet-activating factor, a newly described phospholipid released during acute inflammation, may predispose the gastric mucosa to acute ulceration. This study was performed to evaluate whether this substance might contribute to acute injury through its effects on mucosal microcirculation or by increasing permeability of the gastric mucosa to luminal acid. Platelet-activating factor was infused at a rate of 1 microgram/min directly into the artery supplying a chambered segment of canine gastric corpus and both significantly decreased venous outflow and mucosal blood flow and enhanced the efflux of volume, sodium ions, and potassium ions into the lumen. Thus, as in other capillary beds, platelet-activating factor appeared to induce stasis of flow and local accumulation of interstitial fluids which then leaked into the lumen. Platelet-activating factor did not significantly alter the back diffusion of hydrogen ions into the mucosa. Thus, platelet-activating factor may not directly influence mucosal permeability to luminal acid, and it may predispose the gastric mucosa to acute injury through its effects on the microvasculature and other aspects of the inflammatory process. PMID- 3341533 TI - Drainage for the patient with an uncomplicated cholecystectomy. PMID- 3341534 TI - Long-term results of pancreaticojejunostomy in patients with chronic pancreatitis. PMID- 3341535 TI - Gut reactions. PMID- 3341536 TI - Cholangiovenous reflux pathways as defined by corrosion casting and scanning electron microscopy. AB - Using corrosion casting and scanning electron microscopy of the rat biliary tree, we investigated the site and size of the pathways that allow bacteria to reflux from bile to blood. Nonobstructed rat biliary trees were injected retrograde with methylmethacrylate resin at a constant rate of 0.04 ml/min to volumes of 40, 60, 80, 120, 160, and 200 microliters. The infusion pressure was monitored and a pressure-volume curve was constructed. After polymerization and corrosion in 30 percent potassium hydroxide, the casts were examined with scanning electron microscopy. In addition, to identify the size of the reflux pathways, ceramic particles of 150 A, 1.7 mu, or 10 mu were added to the resin, and the studies were repeated. Finally, intact livers with casted biliary trees were processed and studied by scanning electron microscopy without corrosion. Scanning electron microscopy demonstrated fine anatomic detail of the cholangiovenous reflux pathway. At 40 microliters (20 cm water pressure), normal biliary radicals were filled. Between 40 and 80 microliters (20 to 50 cm water pressure), the cast material refluxed from the bile ductules into the spaces of Mall and Disse and then into the hepatic sinusoids. Filling of sinusoids continued at volumes between 80 to 160 microliters, and filling of collecting veins was seen above 160 microliters. Particles of 1.7 mu and smaller readily refluxed, but there was no sinusoidal reflux of casting material that contained particles of 10 mu. Casting without corrosion showed that the liver parenchyma remained intact. There was no evidence of reflux across hepatocytes. This study shows that cholangiovenous reflux occurs directly from bile ductules through the spaces of Mall and Disse into the hepatic sinusoids. The pathways measure between 1.7 and 10 mu. Since this is the path of least resistance, it may be of greater importance in the reflux of bacteria and toxins than other high-resistance pathways, for example, biliary canaliculi, tight junctions, or hepatocytes. PMID- 3341537 TI - Relationship of postoperative septic complications and blood transfusions in patients with Crohn's disease. AB - We prospectively studied 169 patients with Crohn's disease to determine if postoperative infectious complications could be related to perioperative blood transfusions. Postoperative septic complications developed in 18 of the 69 patients who received more than 1 unit of blood (26 percent) compared with 8 of the 100 patients (8 percent) who received 1 unit of blood or no blood (p = 0.0014). Previous operation, low body weight, and having an ostomy were also related to septic complications. Patients receiving more than 1 unit of blood were significantly more likely to have low preoperative serum albumin levels, to have undergone abdominoperineal or small bowel resection, and to have an ostomy. Postoperative septic complications were significantly related to perioperative blood transfusions after controlling for these potential confounding factors independently by subgrouping and simultaneously by using multiple logistic regression. Blood transfusion may be a more significant factor in postoperative immune suppression and susceptibility to infection than previously recognized. PMID- 3341538 TI - Possible mechanisms of acute pancreatitis induced by ethanol. AB - We investigated the effect of intravenous and intragastric ethanol on pancreatic duct pressure, duct permeability to dextran molecules (20,000 molecular weight), and on the development of acute pancreatitis in an experimental model of the disease. Intragastric ethanol caused a small increase in pancreatic duct pressure (6 to 7 mm Hg) and an increase in duct permeability to dextran. Intravenous ethanol with exclusion of the sphincter of Oddi did not increase pancreatic duct pressure or permeability. Intravenous ethanol and intragastric normal saline solution altered neither pressure nor permeability. Artificial elevation of pancreatic duct pressure alone with no ethanol had no effect on duct permeability. However, when intravenous ethanol was given to produce similar systemic concentrations as achieved in the intragastric experiments (250 mg/dl) and duct pressure was artificially raised, duct permeability was increased. Ethanol concentrations similar to those found in peripheral blood were detected in secretin-stimulated pancreatic juice. Perfusion of the pancreatic duct with activated pancreatic enzymes after intragastric but not intravenous ethanol (that is, only in animals with increased duct permeability) caused acute edematous pancreatitis. Our results confirmed that increased duct permeability was necessary to produce acute pancreatitis in this model, and that this increase in permeability resulted from both a small increase in duct pressure and probably from the toxic metabolic effects of ethanol. PMID- 3341539 TI - Clinical and radionuclide evaluation of Roux-Y diversion for postgastrectomy dumping. AB - From 1973 to 1986, 22 patients underwent Roux-Y gastrojejunostomy for the early postgastrectomy dumping syndrome. In the early years, five patients underwent Roux-Y conversion with the addition of a 10 cm antiperistaltic jejunal segment interposed between the Roux-Y limb and the stomach. Within 4 years, all five patients had the jejunal segment removed due to severe symptoms of gastric retention. These patients underwent reconstruction to create Roux-Y limb only and joined the pool of 17 patients who underwent Roux-Y diversion only for the dumping syndrome. Overall, 19 of 22 patients (86 percent) had almost complete resolution of their dumping symptoms on long-term follow-up. Three patients showed no improvement, two with severe gastric retention and one with recurrent dumping symptoms. Overall, 5 of 22 patients (23 percent) had moderate to severe early and late postoperative gastric retention necessitating medical treatment in three and subsequent near-total gastrectomy in two. Although other procedures such as pyloric reconstruction or the addition of isoperistaltic or antiperistaltic jejunal interpositions have been reported to be equally successful in delaying gastric emptying and resolving dumping symptoms, we have preferred Roux-Y diversion for the treatment of combined alkaline reflux gastritis and dumping or the pure early vasomotor postgastrectomy dumping syndrome. As reported, we have abandoned the use of an antiperistaltic jejunal segment interposed between the stomach and the Roux-Y limb due to the high rate of postoperative gastric retention. PMID- 3341540 TI - Portal hypertension. A fifteen year perspective. AB - Two hundred six consecutive patients were followed from 5 to 15 years after a distal splenorenal shunt operation. Nonalcoholic patients demonstrated nearly twice the survival rate when compared with alcoholic patients. The mean duration of life for the surviving nonalcoholics was 10 years and for the alcoholics, 9 years. We predict that approximately a third of the nonalcoholics will enjoy long term survival. The operative mortality rate was similar in both groups, being about 4 percent. The risk of liver cancer was highest in the male alcoholics, and long-term survival was greater for women in both the alcoholic and nonalcoholic groups. PMID- 3341542 TI - Gastrosphincter of Oddi reflex. AB - Gastric distention is known to stimulate gallbladder contraction as well as gastric acid and pancreatic exocrine secretion by way of neural reflexes. Gallbladder distention, in turn, has been shown to affect sphincter of Oddi motility. Since gastric distention may accompany endoscopic or operative biliary manometry, we tested the hypothesis that gastric distention alters sphincter of Oddi motility. In the prairie dog model, gastric distention with acid (0.1 M hydrochloric acid, pH 1.3) and alkaline (10(-5) sodium hydroxide, pH 8.8) isotonic saline solutions both resulted in significant increases in sphincter of Oddi phasic wave frequency, amplitude, and motility index. Similarly, gallbladder pressure increased during both distention periods, thus confirming the previously described pylorocholecystic reflex. These responses were abolished by systemic pretreatment with atropine, suggesting that this reflex is cholinergically mediated. These data suggest the presence of a gastrosphincter of Oddi reflex whereby gastric distention stimulates sphincter of Oddi motility in the prairie dog. We conclude that gastric distention is an important variable to be controlled when performing endoscopic or operative sphincter of Oddi manometry. PMID- 3341541 TI - Diagnosis of symptomatic alkaline reflux gastritis and prediction of response to bile diversion operation by intragastric alkali provocation. AB - Because accurate diagnosis of the alkaline reflux gastritis syndrome has been elusive, surgical treatment has had a high failure rate, particularly with respect to relief of pain. We have used intragastric infusion of alkali as a provocative test in 147 patients with symptoms and endoscopic findings suggestive of bile gastritis and in 19 asymptomatic control subjects. Subjects received saline solution, 0.1 normal hydrochloric acid, and 0.1 normal sodium hydroxide solutions, as well as their own gastric aspirates in random blinded fashion by a nasogastric tube. There were no complications. A positive test result was defined as pain with sodium hydroxide but not with saline solution or hydrochloric acid infusion. All of the control subjects had negative test results. A total of 87 percent of the symptomatic patients have been followed (mean 4.3 years, minimum 1 year); 47 of those 128 had a Roux-Y gastrojejunal reconstruction to divert duodenal contents from the stomach. Correlation of the test results and the subsequent clinical status showed 87 percent of those with negative test results improved spontaneously or with other treatment versus 15 percent if the test results were positive (p less than 0.001), and 78 percent of those with positive test results had lasting relief of pain after surgical diversion versus a 30 percent success rate if the test results were negative (p less than 0.01). We conclude that positive alkali infusion test results predict that symptoms will likely respond best to surgical diversion of duodenal contents, and that negative test results should be a strong deterrent to surgical diversion. The test is safe, simple, and deserves further trial. PMID- 3341543 TI - Truncal vagotomy as a possible potentiator of gastric atony. AB - To stimulate ulcer patients undergoing operation for gastric outlet stenosis, pyloric obstruction was created in dogs and repaired with pyloroplasty to which was added truncal vagotomy, proximal gastric vagotomy, or no vagotomy. Gastric antral contractile activity after feeding a solid meal was studied before and after repair (2 week period of study). This activity was correlated with the initial lag and regulated phases of solid meal emptying. Five quantified indices of contractile activity measured during the first postprandial hour indicated variable and inconclusive results in the antrum during the lag phase (first 20 minutes). Consistent percentage changes in these indices after obstruction repair were seen during the subsequent regulated phase. Gastric work was reduced 28 to 35 percent, but not work capability (mean area), by pyloric obstruction in the no vagotomy dogs. Reductions seen in proximal gastric vagotomy dogs were not different from those in the no vagotomy dogs. Higher percentages of reduction in amplitude (70 percent) and mean area of contractions (53 percent) occurred after truncal vagotomy compared with what occurred in the no vagotomy dogs. Mean area was also reduced more compared with what occurred in the proximal gastric vagotomy dogs. These data indicate that the reduced gastric work after feeding and impaired work capability caused by truncal vagotomy when superimposed on that produced by pyloric obstruction may exaggerate gastric atony and contribute to the delayed recovery of gastric emptying seen in the clinical setting. PMID- 3341544 TI - Anorectal function and defecation dynamics in patients with rectal prolapse. AB - Seven female patients with clinical rectal prolapse and nine healthy female control subjects were studied with anorectal manometry, external sphincter electromyography, and a saline continence test. Resting anal tone, maximum voluntary squeeze, and rectal functional capacity were significantly decreased in the rectal prolapse patients (p less than 0.02). During defecation attempts, external sphincter or pelvic floor electromyographic activity decreased in all of the control subjects, whereas six prolapse patients showed increased electromyographic activity and one had no change in activity (p less than 0.01). Continence to saline solution was also significantly impaired in prolapse patients (p less than 0.001). Postoperative studies in three patients who underwent repair revealed persistence of abnormal anorectal function and defecation dynamics. Patients with rectal prolapse have impaired resting and voluntary sphincter activity, decreased functional rectal capacity, and impaired continence. The failure of normal relaxation of the external sphincter or pelvic floor during defecation attempts, as demonstrated in the patients described herein, may contribute to the development of prolapse and denervation sphincter injury seen in such patients. PMID- 3341545 TI - Our greatest failure. PMID- 3341546 TI - Endoscopy versus double-contrast barium enema in the evaluation of patients with symptoms suggestive of colorectal carcinoma. AB - Two hundred seventy-six patients with positive findings on a stool guaiac test, hematochezia, a change in bowel habits, or a family history of colorectal carcinoma were referred to the colorectal clinic for further investigation. There were 105 men and 171 women. All patients underwent examination with the 65 cm flexible sigmoidoscope. Patients with no abnormalities on endoscopy underwent a double-contrast barium enema. If the barium enema revealed a polyp or other suspicious pathologic process, the patient was referred for colonoscopy. In 258 patients, findings of barium enema and flexible sigmoidoscopy were in agreement. The findings in 178 of these examinations were completely negative, and in the remaining 80 cases flexible endoscopy and barium enema revealed diverticulosis. In an additional 18 patients, negative findings on flexible sigmoidoscopy were followed by positive findings on barium enema. Thirteen of these 18 patients (72 percent) had negative findings on colonoscopies and therefore had false-positive findings on barium enema. In the remaining five patients (28 percent), an unsuspected colonic carcinoma or premalignant polyp was discovered on barium enema and documented by colonoscopy. Also, in four of these five patients, colonoscopy found additional polyps that were not seen on barium enema. PMID- 3341547 TI - Reoperation directed by carcinoembryonic antigen level: the importance of a thorough preoperative evaluation. AB - Many asymptomatic patients suspected to have recurrent colorectal cancer based on an elevated carcinoembryonic antigen level will be spared unnecessary operation if strict attention is paid to their preoperative evaluation. Liver and renal function should be assessed. Unresectable extraabdominal and intraabdominal recurrence or metastases should be excluded. Patients being evaluated for recurrence after curative resection of a rectosigmoid cancer should undergo a bone scan. Having satisfactorily ensured normal results for these investigations, the surgeon should then proceed to search for an intraabdominal source of tumor recurrence. PMID- 3341548 TI - Preoperative evaluation with radionuclide brain scanning and computerized axial tomography of the brain in patients with breast cancer. AB - To determine the roles of radionuclide brain scanning and computerized tomography of brain in the pretreatment evaluation of patients with primary and locoregional recurrence of breast cancer, we reviewed the clinical and radiologic findings in 226 patients with breast cancer who underwent one of these scans either preoperatively or within 6 weeks of operation and in 34 patients presenting with locoregional recurrence. Four of 131 radionuclide brain scans in primary breast cancer suggested calvarial metastasis, and the findings were confirmed with bone scans and skull radiographs. One of 95 computerized tomographic scans of the brain showed brain metastasis, and this patient had profound neurologic deficits. With respect to locoregional recurrence, the results of 2 of 23 radionuclide scans and 1 of 11 computerized tomographic scans were positive. All three patients had clinical evidence for brain metastasis. We conclude that in the absence of signs and symptoms, routine evaluation for brain metastasis is not justified in primary and locoregional recurrence of breast cancer. PMID- 3341549 TI - Narrowing resection margins for patients with low-risk melanoma. AB - Surgeons hesitate to accept lesser cancer operations for several reasons. Paramount, however, is the fear that they might jeopardize cure rates by inadvertently leaving residual tumor behind. In cutaneous melanoma, for example, wide excision of the primary tumor site, usually in combination with skin grafting, has been the standard for years. Recently, as the biologic characteristics of this neoplastic system have become better understood, a subset of patients has been identified who can be cured readily by surgical excision alone. It is in this low-risk group of patients that lesser margins of excisions have been advocated. To date, a majority of surgeons have not accepted this thesis. In an effort to study this further, one of us prospectively treated 45 patients with thin, low-risk melanomas by conservative excision of their primary tumor sites. The margins invariably were 2 cm or less, and two thirds of the patients were operated on as out-patients utilizing local anesthesia. After a mean follow-up period of 36 months, no recurrences of melanoma developed. Acceptance of this treatment appears appropriate in this subset of patients. PMID- 3341550 TI - Effect of cyclosporin A on hepatocyte proliferation after partial hepatectomy in rats: comparison with standard immunosuppressive agents. AB - The effects of cyclosporin A on the regenerating liver were studied in rats after partial hepatectomy and were compared with those of conventional immunosuppressants such as methylprednisolone and azathioprine. In Group I, a standard hepatectomy removing two thirds of the organ was performed. In Group II, an oral dose of 10 mg/kg of cyclosporin A was given 1 day before and immediately, 24 hours, and 48 hours after the same hepatectomy. In Groups III and IV, azathioprine and methylprednisolone were administered in 8 mg/kg doses by way of the tail vein by the same protocol as in Group II. The mortality rate, liver weight restoration, and histologic and mitotic characteristics of the liver remnants, as well as serum levels of animotransferase, total bilirubin, and creatinine were examined from 24 hours to 10 days after the operation. Azathioprine and methylprednisolone substantially suppressed hepatocyte mitosis when compared with the control group; however, cyclosporin A treatment did not inhibit, but may, in fact, have stimulated liver cell proliferation. Changes in other parameters coincided with this phenomenon. The noninhibitory effect of cyclosporin A on liver regeneration has also been discussed. PMID- 3341551 TI - Segmental splenectomy using the ultrasonic surgical aspirator. AB - The technique described seems to significantly decrease blood loss in segmental splenectomy. Resection of the damaged splenic segments offers the potential advantage of reducing rebleeding and secondary hemorrhage from sites of repaired lacerations. Also, the viable splenic fragment that is left behind may afford protection from postsplenectomy sepsis. The ultrasonic surgical aspirator seems well suited for the purpose of segmental splenectomy in both the trauma and staging laparotomy setting. PMID- 3341552 TI - Infection as a contributory cause of death in patients hospitalized for motor vehicle trauma. AB - The age and length-of-stay specific incidence of fatal infections and the percentage of deaths due to infection were determined in a population-based sample of patients hospitalized for more than 2 days for motor vehicle injuries. The percentage of deaths due to infection was determined from a statewide sample of death certificates, and the patient fatality rates for hospitalized motor vehicle crash injury patients were determined from statewide Professional Activities Study data. Fatal pulmonary infections were far more common than fatal nonpulmonary infections. The incidence rate of fatal pulmonary infection was highest among those with hospital stays of 7 to 28 days and among those 70 years of age or older. Incidence rates varied substantially by age and length of hospital stay from a low of 8 deaths per 100,000 patient-days for adult female patients with stays longer than 28 days to a high of 102 deaths per 100,000 patient-days for elderly men with stays of 7 to 28 days. The incidence rates documented in this study may improve the identification of blunt trauma patient groups with the greatest need for prophylactic antiinfective measures. PMID- 3341553 TI - Intraabdominal sepsis after hepatic trauma. AB - In a review of 58 patients who survived liver trauma seen at Boston City Hospital, 10 patients had 13 intraabdominal abscesses and 1 died from overwhelming sepsis. Multivariate analysis of risk factors revealed that the number of units of perioperative, postoperative, and total blood transfused were each highly significant (p less than 0.0001). Mode of injury, hepatic resection, gastrointestinal tract perforation, and the number of associated injuries were not significant risk factors when transfusion requirements were accounted for. Fever and leukocytosis were unreliable predictors of abscess formation. The available literature suggests a strong relationship between intraperitoneal bleeding and septic complications. PMID- 3341554 TI - Prevention of posttraumatic pulmonary platelet trapping by portacaval transposition. AB - Significant soft-tissue trauma induces platelet activation, aggregation, and sequestration in the lungs. This pulmonary trapping is due either to the size of the platelet aggregates or to changes in the pulmonary microvasculature. To evaluate which one of these mechanisms is responsible for the trapping, we performed portacaval transposition in one group of pigs, making the liver the first receiving capillary bed for blood from the trauma sites in the lower extremities. One week after the operation, the platelets were labeled with indium oxine and reinfused, and the operated animals and a group of six control animals were subjected to standardized soft-tissue trauma to the lower extremities. Sequestration of platelets in the lungs and in the liver was registered dynamically before and for 90 minutes after the trauma. Soft-tissue trauma induced platelet sequestration in the liver in the operated group (p less than 0.01) and in the lungs in the control group (p less than 0.01). Trapping was paralleled by a decrease in the number of circulating platelets. This study has indicated that posttraumatic pulmonary platelet trapping is caused by platelet activation at the trauma sites and not by changes in the pulmonary microvasculature. PMID- 3341555 TI - Endotoxemia in obstructive jaundice. Observations on cause and clinical significance. AB - Perioperative endotoxemia was detected in 24 of 40 patients who underwent operation for obstructive jaundice (bilirubin level greater than 5.8 mg/dl). Endotoxemia was associated with an increased admission serum bilirubin level (p less than 0.05) and white blood cell count (p less than 0.05) and a decreased hematocrit value (p less than 0.05), but there was no significant association with other established preoperative risk factors. Patients with preoperative endotoxemia had a decreased immunoglobulin M anti-J5 endotoxin titer (p less than 0.05) and a decreased serum bile acid concentration (p less than 0.05). Preoperative endotoxemia was associated with reduced creatinine clearance before and after operation (p less than 0.05). There was no association between endotoxemia and clinical sepsis, gram-negative infection, or small-bowel colonization. Patients who died had increased preoperative serum fibrin degradation products (p less than 0.05). PMID- 3341556 TI - Influence of surgeons' experience on postoperative sepsis. AB - A prospective study was performed on 635 patients with appendicitis operated on by 7 trainees and 119 patients operated on by 6 senior surgeons with more than 8 years of surgical experience. In patients with normal appendices, postoperative sepsis was extremely low. For early and late appendicitis, the infection rates of the trainees decreased as experiences accumulated, but they were still higher than that of the senior surgeons. The difference in infection rates in acute appendicitis did not reach statistical significance between any of the training stages and between the various stages and the rate of the senior surgeons. The differences in infection rates in late appendicitis between stage 1 and stage 3 was significant, as was the difference in infection rates between stage 1 and the infection rate of the senior surgeons. Therefore, we have concluded that overall, the limited experience of trainees is related to the rate of postoperative sepsis in late appendicitis, although the infection rates of individual trainees vary a lot. PMID- 3341557 TI - Management of aortic prosthetic infections. AB - Infections of aortic vascular prostheses remain a dreaded complication. Although removal of the graft has generally been recommended in the literature, the role of lesser procedures, the need for alternate revascularization, and a precise plan of attack are ill defined. We have treated 18 patients with infection of aortic prostheses. Specific risk factors potentially promoting infection included reoperation, septic complications, or gastrointestinal entry at the time of graft placement. Clinical signs of infection included chronic draining sinus in eight patients, localized groin abscess in three patients, groin swelling in four patients, gastrointestinal bleeding in two patients, and pseudoaneurysm in one patient. Treatment by local therapy, including catheter irrigation of sinus tracts, debridement, and local antibiotics, resulted in failure in eight of nine patients. If the sinogram of a groin sinus showed no communication with the body of the graft, resection of a graft limb was successful in 66 percent of the patients. If the sinus communicated with the body of the graft, total resection was mandatory. When total excision was necessary, all patients required revascularization by means of an extraanatomic bypass. The mortality rate was 33 percent and was primarily due to bleeding fistulas. An aggressive approach to this serious problem with early graft excision is encouraged. PMID- 3341558 TI - Complications of acute diverticulitis of the colon: improved early diagnosis with computerized tomography. AB - We have evaluated the diagnostic role of computerized tomography in 42 patients suspected clinically of having a complication of acute diverticulitis (abscess, colovesical fistula, or both). Diverticular abscesses were confirmed at operation in 10 patients. All 10 patients were diagnosed preoperatively on computerized tomography by the triad of diverticula, a segmentally thickened colon, and extravisceral fluid collection with (6 patients) or without (4 patients) associated gas. Contrast enema study suggested the presence of a diverticular abscess in only two of eight patients studied. Colovesical fistulas were confirmed in 12 patients. Eleven of 12 were diagnosed preoperatively on computerized tomography by the triad of air in the bladder, thickened colon adjacent to an area of thickened bladder, and the presence of colonic diverticula. Contrast enema examinations demonstrated the fistula in only three of eight patients studied. The remaining 20 patients proved to have uncomplicated acute diverticulitis. Findings on computerized tomography included the presence of a segmentally thickened colon with diverticula but without the findings of an abscess or a colovesical fistula. Computerized tomography correctly visualized acute diverticular complications in 21 of 22 patients and it excluded an abscess or fistula in all 20 patients with uncomplicated acute diverticulitis who were suspected of having a diverticular complication. Computerized tomography is the most sensitive and specific test for diagnosing complications of acute diverticulitis. It should be an early consideration in patients with suspected diverticular abscesses or fistulas so that appropriate therapy is not delayed. PMID- 3341559 TI - Circulating immune complex, endotoxin, and biliary infection in patients with biliary obstruction. AB - Immunoglobulin A-containing circulating immune complexes, immunoglobulin G containing circulating immune complexes, and endotoxin were measured in the sera of patients with obstructive jaundice. The bile of patients with percutaneous transhepatic biliary drainage was also cultured for bacteriologic studies. There was a significantly positive correlation between the endotoxin levels and both immunoglobulin A-containing circulating immune complex and immunoglobulin G containing circulating immune complex. The endotoxin levels of the patients with gram-negative infections were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin G-containing circulating immune complex levels of the patients with bacteria in bile were significantly increased compared with those of the patients with sterile cultures. The immunoglobulin A-containing circulating immune complex levels of the patients with bacteria in bile were slightly increased, but the difference did not reach statistical significance. These results indicate that one of the causes of increased circulating immune complex levels may be endotoxemia in combination with biliary infection in patients with biliary obstruction. PMID- 3341560 TI - Bacteriuria in appendicitis. AB - The value of bacteriologic findings in patients with acute appendicitis was studied. Routine urinary culture specimens were taken preoperatively from 194 children (mean age 11 +/- 3 years) undergoing emergency appendectomy. Bacteria were found in culture specimens of urine from 26 of 156 patients with acute appendicitis. The bacteriuria was correlated to the position of the appendix, the duration of disease, and the degree of inflammatory changes in the appendix. The results suggest direct spread of bacteria from the inflamed appendix to the urinary tract due to close anatomic relationship and to the severity of the inflammatory changes. That this spread of bacteria can have clinical significance cannot be excluded. Urinary sedimentation study is of no use in the diagnosis of acute appendicitis. PMID- 3341561 TI - Peritoneal lavage in the diagnosis of acute peritonitis. AB - The study was aimed at determining the value of peritoneal lavage as an aid in the diagnosis of acute peritonitis when the diagnosis could not be made by ordinary clinical criteria. Thirty patients were studied prospectively. Twenty five of the patients were suspected of having peritonitis but doubt existed because of an unreliable history or equivocal or confusing abdominal signs. Five remaining patients were comatose and an intraabdominal source of sepsis needed to be excluded. The technique of lavage and criteria for diagnosis have been presented herein. There were 10 true-positive results, no false-positive results, 19 true-negative results, and one false-negative result (positive predictive value 100 percent, confidence level 95 percent). There were no complications due to the test. Peritoneal lavage is a useful method of diagnosing or excluding peritonitis in patients with confusing abdominal signs. Negative results of laparotomy or prolonged observation may thus be obviated in such patients. PMID- 3341562 TI - Effect of cephalosporins on fascial healing after celiotomy. AB - A 7 day course of either cefonicid or cefazolin significantly reduced mean wound breaking weight after midline celiotomy in Sprague-Dawley rats compared with control animals. This detrimental effect was not seen when each drug was administered as a single preoperative dose. Even a 3 day course of cefonicid was associated with a significant reduction in the weight required to disrupt a healing abdominal closure. An increased incidence of incisional hernias was also noted among animals treated for 7 days with cefonicid or cefazolin. Shorter antibiotic regimens were not associated with an increased frequency of incisional herniation. PMID- 3341563 TI - Cardiac electrophysiologic effects of lidocaine and bupivacaine. AB - The cardiac electrophysiologic effects of bupivacaine (B) and lidocaine (L) were evaluated in an isolated rabbit Purkinje fiber-ventricular muscle model to determine the effects of a) progressively increasing and b) decreasing concentrations of B and L on transmembrane action potentials. Bupivacaine (3 and 5 micrograms/ml) significantly decreased diastolic resting potential, maximum rate of depolarization, and action potential amplitude. Lidocaine (10-20 micrograms/ml) also decreased maximum rate of depolarization and action potential amplitude, but the decreases were significantly different from those produced by B. High concentrations of B (30 micrograms/ml) and L (100 micrograms/ml) resulted in delayed conduction between Purkinje fibers and ventricular muscle cells and, ultimately, conduction blockade. The duration of conduction blockade was significantly longer with B than with L. The results of this study indicate that B produces electrophysiologic changes in cardiac tissue that may produce ventricular arrhythmias of a reentrant type. PMID- 3341564 TI - Laser-induced pain for evaluation of local analgesia: a comparison of topical application (EMLA) and local injection (lidocaine). AB - High-energy lasers are suitable for experimental pain stimulation because they selectively activate the polymodal nociceptors. Argon laser light penetrates deep into the skin and makes this laser type preferable for simulating pain arising from surgical skin incisions. Short argon laser pulses were applied to the skin and three parameters were quantified before and during analgesia; sensory threshold, pain threshold, and the pain-related cortical response (latency and amplitude). Determination of sensory and pain thresholds made it possible to distinguish between two levels of analgesia; the pain block, where no pain was felt but other sensations were still perceived; and total sensory block, where the laser stimulus elicited no sensations of any type. The analgetic effects of cutaneous injections of lidocaine and topical application of EMLA (eutectic mixture of local anesthetics) cream were evaluated and compared by means of the introduced parameters. Lidocaine produced total sensory block almost immediately after injection, which was associated with the absence of cortical response to cutaneous laser stimulation. When the EMLA cream was applied for 15 minutes, both sensory and pain thresholds increased. During the next 30 minutes after removal of the cream, the thresholds increased further. The increase in analgetic effect after removal of the cream was studied using different times (15, 30, 60, 80, 100, and 120 minutes) for topical EMLA cream application. Total sensory block was reached 20 minutes after removal of application for 80 minutes or immediately after removal of the cream after it was applied for 100 or 120 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341565 TI - The overstated risk of preoperative hypokalemia. AB - To examine the relation between preoperative hypokalemia and frequency of intraoperative arrhythmias, Holter monitoring was employed in 447 patients undergoing major cardiac or vascular operations, the group at greatest risk for life-threatening arrhythmias. Based on serum potassium levels measured immediately before surgery, 57% of patients were normokalemic (greater than or equal to 3.6 mEq/L), 34% hypokalemic (3.1-3.5 mEq/L), and 9% severely hypokalemic (less than or equal to 3.0 mEq/L). No arrhythmia occurred at any time in 63% of patients and minor arrhythmias (premature atrial and occasional premature ventricular contractions) occurred in 16%. Frequent or complex ventricular ectopy appeared before and during operation in 92 patients (21%) but was not related to preoperative potassium level or history of long-term diuretic therapy. Frequent and complex ventricular arrhythmias were more common in patients with a history of long-term digoxin therapy or congestive heart failure. Even among these patients, hypokalemia or diuretic therapy did not increase the incidence or severity of ectopy. These data fail to support the common practice of delaying operation for acute potassium replacement in patients whose preoperative serum potassium is less than normal, even in the presence of cardiovascular disease. PMID- 3341566 TI - Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs. AB - The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension. PMID- 3341567 TI - Inadvertent subdural injection: a complication of an epidural block. AB - Twenty-one hundred eighty two consecutive lumbar epidural injections were studied to determine the incidence of inadvertent subdural block retrospectively. A subdural block is defined as an extensive neural block in the absence of subarachnoid puncture, that is out of proportion to the amount of local anesthetic injected. Subdural injection is a complication of epidural block that probably occurs more frequently than previously recognized. An earlier report has estimated the incidence of subdural block to be 0.1%. This study, however, reports an incidence of 0.82% from a sample size of 2182 patients. Cadaveric dissection was also performed, further clarifying the presence and anatomic position of the subdural space. PMID- 3341568 TI - Monitoring of arterial hemoglobin oxygen saturation using a tongue sensor. PMID- 3341569 TI - Early detection of patent foramen ovale by two-dimensional contrast echocardiography for prevention of paradoxical air embolism during sitting position. PMID- 3341570 TI - Megaloblastic anemia and brief exposure to nitrous oxide--a causal relationship. PMID- 3341571 TI - Abstracts of papers and posters presented at the International Anesthesia Research Society 62nd congress. San Diego, California, March 5-9, 1988. PMID- 3341572 TI - What difference does pulse oximetry make? PMID- 3341573 TI - The electrophysiologic actions of lidocaine and bupivacaine in the isolated, perfused canine heart. AB - To discriminate between the electrophysiologic and arrhythmogenic effects of lidocaine and those of bupivacaine, isolated, perfused canine hearts were exposed to toxic concentrations of the drugs. The preparations included the sinus node and right atrium, and, in some cases, the AV node and interventricular septum as well. Action potentials were recorded from these areas, and right atrial twitch amplitude and spontaneous rate and rhythm were monitored. Heart rate was depressed in a dose-dependent manner by both drugs, as was atrial twitch amplitude. In the absence of arrhythmias, the spontaneous rate decreased less than 30% with lidocaine up to 50 micrograms/ml, and with bupivacaine up to 5 micrograms/ml. The twitch depression reflected a potency ratio for bupivacaine (mol. wt. 288) to lidocaine (mol. wt. 234) on a mass basis of 8.1:1. The most prominent arrhythmia found was sinoatrial block, which was caused by both drugs with a potency ratio for bupivacaine to lidocaine of 15.4:1 and was reversed by 0.02 microgram/ml norepinephrine. Sinus arrhythmias, block of retrograde conduction from AV node to atrium, and irregular rhythms originating within the AV node were observed with both drugs at concentrations similar to those which produced sinoatrial block. The atrial action potential revealed decreased upstroke velocity, overshoot, and height with both lidocaine and bupivacaine, with potency ratios (bupivacaine:lidocaine) ranging from 15:1 to 26:1. In septal cells, both drugs depressed upstroke velocity, and bupivacaine lengthened action potentials by up to 14%, but lidocaine did not. The major difference between bupivacaine and lidocaine in this study was the higher potency of the former agent with respect to electrophysiologic end-points. PMID- 3341574 TI - Rate of inactivation of human and rodent hepatic methionine synthase by nitrous oxide. AB - The rate of inactivation of hepatic methionine synthase by nitrous oxide has been determined in 22 patients undergoing laparotomy during general anesthesia, including 70% nitrous oxide. Mean half-time of inactivation was 46 min. Metabolic consequences of nitrous oxide are, thus, critically dependent on the duration of anesthesia, and are unlikely to be significant during exposures of less than 40 min. Inactivation of methionine synthase is very much more rapid in the rat exposed to 50% nitrous oxide, with a half-time of 5.4 min. PMID- 3341575 TI - Anatomy of the human lumbar epidural space: new insights using CT-epidurography. AB - The anatomy of the lumbar epidural space was demonstrated in 40 patients by computed tomography (CT) examinations performed after epidural injection of noninonic radiographic contrast material into the sacral caudal canal via percutaneous catheter. Radiologic evaluation of the epidural space was performed to evaluate possible disc herniation or other pathologic encroachments on the epidural space. In all 40 patients, the examinations showed the posterior epidural space to be divided by the plica mediana dorsalis and an additional transverse connective tissue plane not previously described. The compartmentalized nature of the space may be, at times, responsible for entrapment and coiling of epidural catheters, despite satisfactory technical performance of catheterization for epidural anesthesia. Thirty-one of 40 patients demonstrated a greater amount of fatty tissue within the junctions of the posterior midline epidural connective tissue structures, producing a bulky triangular-shaped structure which might be an impediment to catheterization. The divisions of the anterior and posterior epidural spaces are seen to be more complex than previously described. PMID- 3341576 TI - Mechanism for slowing of heart rate and associated changes in pulmonary circulation elicited by cold injectate during thermodilution cardiac output determination in dogs. AB - The authors investigated the mechanism for slowing of heart rate (HR) and associated changes in the pulmonary hemodynamics caused by cold injectate during thermodilution method. To clarify whether the slowing of HR after cold injectate is due to the cooling of the sinoatrial (SA) node or a reflex mediated by the autonomic nerves, we directly measured the myocardial temperature of the SA node region by a thermistor probe, and evaluated the HR responses to iced injectate after autonomic blockade in anesthetized dogs. Additionally, pulmonary blood flow (PBF) was continuously measured by an electromagnetic flowmeter during the delivery of injectate. The direction and magnitude of changes in HR after injectate were significantly dependent upon the injectate temperature (P less than 0.01). Thereby, the changes in HR correlated well with those in myocardial temperature of the SA node region (r = 0.987, P less than 0.01). However, the HR responses to injectate were unaffected by cervical vagotomy or stellate ganglionectomy. A significant decrease in PBF was noted in most cases during the slowing of HR. It was concluded that the slowing of HR after cold injectate during thermodilution in dogs is primarily due to the direct cooling of the SA node. PMID- 3341577 TI - Comparative coronary vascular reactivity and hemodynamics during halothane and isoflurane anesthesia in swine. AB - To assess the dose-response effects of isoflurane and halothane anesthesia on hemodynamics and coronary artery reactivity, the authors studied myocardial hyperemic responses following brief single artery flow arrests in 21 open chest, isocapnic swine in which arterial blood pressures and cardiac outputs were recorded. A specially designed Doppler probe was used to measure the peak and time course of coronary blood flow velocity in the left anterior descending coronary artery (LAD) after 15-s LAD occlusions. The ratio of peak velocity of blood flow to resting velocity (coronary reserve), relative repayment of flow debt, and duration of hyperemic responses were studied. Surgery was performed at MAC end-tidal concentrations ([Et]isoflurane = 1.45%. [Et]halothane = 1.25%) of isoflurane (n = 7) or halothane (n = 7), and recordings were made after 15-min steady state [Et]agent at 0.5, 1, 1.25, 1.5, 1.75, 2 MAC, and further 0.5 MAC increments until the demise of each animal. To compare coronary reactivity at similar coronary pressures, an aortic snare was used to elevate arterial pressures in a third group of halothane anesthesized pigs (n = 7) to those in the previously studied isoflurane group at each MAC level. There were three major differences between halothane and isoflurane. First, cardiac depression (reduction in arterial pressure, cardiac output, and stroke volume) was less with isoflurane compared with halothane anesthesia. Second, with halothane anesthesia, there was a marked decrease in coronary reactivity independent of coronary perfusion pressures with marked, dose-dependent reductions in both coronary reserve and relative flow repayment. During isoflurane anesthesia, coronary reactivity and coronary reserve was well preserved within physiologic limits up to 1.75 MAC [Et]. Third, halothane anesthesized pigs died in cardiac collapse at much lower agent concentrations than with isoflurane (no animals survived 1.75 MAC halothane, whereas all animals survived 2.5 MAC isoflurane). Therefore, pigs anesthesized with isoflurane had greater coronary reserve, better preserved cardiac function, and greater tolerance to increasing agent concentration than pigs anesthesized with halothane. PMID- 3341578 TI - Testing computer-controlled infusion pumps by simulation. AB - The pharmacokinetic behavior of intravenous anesthetic drugs can be described by two- or three-compartment models. Rapid achievement and maintenance of steady plasma concentrations of these drugs requires a complicated delivery scheme, perhaps best controlled by a computer. The authors developed a method of simulating the performance of a computer-controlled infusion pump from the differential equations describing drug transfer between compartments. They also derived a mathematically simple and flexible approximate solution to these equations using Euler's numerical method. They incorporated this approximate solution into a computer-controlled infusion pump for intravenous drugs. They tested their pump by simulating the administration of fentanyl to a hypothetical patient whose fentanyl pharmacokinetics were described by a three-compartment model. The exact analytical solution served as the standard of comparison. The approximation technique, using a 15-s interval between model updates, had a maximum error of 0.35 ng.ml-1, and rapidly converged on the exact solution. The simulations revealed oscillations in the system. The authors suggest that such simulations be used to evaluate computer-controlled infusion pumps prior to clinical trials of these devices. PMID- 3341579 TI - Atracurium infusion in infants. PMID- 3341580 TI - Ventilatory management assisted by cardiopulmonary bypass for distal tracheal reconstruction in a neonate. PMID- 3341581 TI - Effect of three anesthetic techniques on the success of extracorporeal shock wave lithotripsy in nephrolithiasis. PMID- 3341582 TI - Changes in oxygen saturation following general anesthesia in children with upper respiratory infection signs and symptoms undergoing otolaryngological procedures. PMID- 3341583 TI - Pulse oximeter desaturation due to methemoglobinemia. PMID- 3341584 TI - Transesophageal atrial pacing for the treatment of dysrhythmias in pediatric surgical patients. PMID- 3341585 TI - Epidural analgesia with low-dose bupivacaine and fentanyl for labor and delivery in a parturient with severe pulmonary hypertension. PMID- 3341586 TI - Negative middle ear pressure and postoperative vomiting in pediatric outpatients. PMID- 3341587 TI - Midazolam in obstetric anesthesia--a reply. PMID- 3341588 TI - Epidural ketamine does not produce analgesia. PMID- 3341589 TI - Percutaneous transtracheal high-frequency jet ventilation as an aid to fiberoptic intubation. PMID- 3341591 TI - Carboxyhemoglobin and pulse oximetry. PMID- 3341590 TI - Hazards of a new system for placement of endotracheal tubes. PMID- 3341592 TI - A case of eye injury from a reusable anesthetic mask. PMID- 3341593 TI - Epiglottitis in young infants. PMID- 3341594 TI - Simple foot restraint. PMID- 3341595 TI - Measurement of the longitudinal distribution of pulmonary vascular resistance from pulmonary artery occlusion pressure profiles. PMID- 3341596 TI - Artifactually low cardiac outputs resulting from a communication between the proximal and distal lumens of an Edwards pacing thermodilution Swan-Ganz catheter. PMID- 3341597 TI - Another source of artifact in the pulmonary artery pressure waveform. PMID- 3341598 TI - Isoflurane and the coronary circulation. PMID- 3341599 TI - Hypermetabolism precipitated by a monoamine oxidase inhibitor. PMID- 3341600 TI - Axillary block of the brachial plexus: "you can't get there from here...". PMID- 3341602 TI - Selective block of the nerves of the brachial plexus. PMID- 3341601 TI - Use of a nerve stimulator for peripheral nerve blocks. PMID- 3341603 TI - Does halothane protect against hypoxia? PMID- 3341604 TI - Intermittent claudication: predictors and outcome. AB - The authors reviewed 460 patients with intermittent claudication. With primarily conservative management, these patients were followed for an average of 4.1 years (one to ten years). The mean age was 71.7 years, ranging from thirty-six to eighty-four years; 55.9% were males. The subsequent follow-up study revealed that the status of 44.1% of the patients with underlying arterial insufficiency deteriorated. Eventually, they underwent vascular surgery for limb-threatening ischemia. From this study, the analysis of the parameters could predict the clinical outcome of intermittent claudication at the time of initial and follow up evaluation. During initial evaluation, when the ankle brachial index (ABI) was higher than 0.7 or when follow-up evaluation did not show a decrease of ABI by 0.15, the chance of favorable outcome was increased by 2.4 and 1.6 times respectively. When the ABI was less than 0.5 at the initial evaluation and decreased 0.15 or more during follow-up studies, the risk of requiring vascular surgery for limb salvage increased by 3.8 and 1.9 times, respectively. The onset of major vascular events in other areas appeared to influence the time of significant deterioration in the lower limb arterial disease, indicating multifactorial and systemic contribution in the natural history of intermittent claudication. In this homogeneous patient population with arterial insufficiency referred to the vascular surgeon, conservative management with strong supervision for smoking cessation, exercise, diet control, body weight reduction, and medical regimen can modify the natural course of intermittent claudication and associated vascular problems. PMID- 3341606 TI - Transient left atrial mobile thrombus in acute myocardial infarction--a case report. AB - The authors report a fifty-year-old woman with acute inferior myocardial infarction in whom left atrial mobile thrombus was found by echocardiography. They believe this to be the first echocardiographic documentation of such a thrombus after acute myocardial infarction. The combination of the stagnant flow in the left atrium due to atrial ischemia, the low output state due to left ventricular dysfunction, and the hemoconcentric tendency from use of diuretics might have played a role in the present thrombus formation. The thrombus was safely lysed without complication after intravenous urokinase. PMID- 3341605 TI - Congenital brachial artery aneurysm in an infant--a case report. AB - An arterial aneurysm of any kind is rare in infancy, and one that occurs in the brachial artery is probably even more rare; when such an aneurysm is asymptomatic and congenital, it must be exceedingly rare. One such unique case is described herein, together with a brief review of the literature. PMID- 3341607 TI - Behcet's disease with chylothorax--case report. AB - Behcet's disease is a systemic disease primarily affecting the eye, genital, and oral mucosa but is known to have various rare complications. A patient with a twenty-year history of Behcet's disease was admitted owing to dyspnea caused by massive chylothorax. Administration of corticosteroid, heparin, and urokinase was ineffective, but the thoracic fluid was well controlled by pleuropexy with Broncasma Berna. Chylothorax complicating Behcet's disease is extremely rare, having been reported in only 2 cases. PMID- 3341608 TI - Syndrome of coronary artery spasm of normal coronary arteries. Clinical and angiographic features. AB - To define the clinical and angiographic features of the syndrome of spasm of angiographically normal coronary arteries, 77 patients with spasm and fixed angiographically normal coronary arteries, 77 patients with spasm and fixed coronary stenosis equal to or greater than 50% (group A) were compared with 35 patients with spasm and normal or minimally diseased coronary arteries (group B). Statistically significant differences between groups A and B were as follows: the incidence of rest angina (50.6% vs 85.7%; p less than 0.01) and mixed angina (32.5% vs 5.7%; p less than 0.01); the appearance of ST segment depression (53.3% vs 16%; p less than 0.01) and no electrocardiographic changes during stress test (35.6% vs 76%; p less than 0.01); and the tendency for arteriographically documented spasm to be focal (87.5% vs 71.4%; p less than 0.05) and to affect only one vessel (76.6% vs 57.1%; p less than 0.05). No differences were found between groups A and B in major coronary risk factors, history of previous myocardial infarction, electrocardiographic abnormalities at rest or during pain episodes, or arteries affected by spasm. Thus, angina appearing exclusively at rest is the main clinical feature of spasm of normal coronary arteries. The electrocardiogram, whether at rest or during pain episodes, has no value for predicting the existence of underlying coronary lesions, whereas stress testing does. Spasm of normal arteries tends to be more diffuse than that superimposed on organic lesions and to affect more than one artery, suggesting different mechanisms in the genesis of both types of spasm. PMID- 3341609 TI - Saluretic and diuretic effects of antihypertensive nitrendipine monotherapy in man. AB - The effects of acute (single-dose) and chronic (26-day) therapy with nitrendipine on renal function were evaluated in 10 patients with mild to moderate hypertension. The patients were studied during three phases: for one week while on a constant diet containing 100 mEq of sodium and 80 mEq of potassium daily and receiving placebo, after administration of a single 20-mg oral dose of nitrendipine, and during one week of treatment with nitrendipine at 10 mg twice daily. After two weeks of outpatient treatment at 10 or 20 mg twice daily, the patients were readmitted and reevaluated while on controlled diets. Isotopic determinations of glomerular filtration rate, effective renal blood flow, blood volume, and cardiac output were made during each phase, and free water clearance and osmolar clearance following a water load were measured; during the periods of hospitalization, 24-hour urinary creatinine and electrolyte excretion were assessed. A significant decrease in blood pressure occurred during both the acute and chronic phases as compared with the placebo phase. During the first week of treatment with nitrendipine, a significant increase in urinary sodium excretion over control values was observed, with a mean deficit of 148 +/- 7 mEq (p less than 0.001); a mean weight loss of 1.0 +/- 0.1 kg during this period was also significant (p less than 0.05). No substantial changes in glomerular filtration rate, renal blood flow, blood volume, cardiac output, plasma renin activity, and levels of plasma catecholamines or urinary aldosterone from control values were noted during either the acute or chronic phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341611 TI - Bronchial hyperresponsiveness in younger children with asthma. AB - We have previously reported a new technique of evaluating bronchial responsiveness by monitoring the transcutaneous oxygen pressure (tcPO2). This method is so simple, painless, and effortless with high reproducibility that it is possible to use the technique on children as young as 2 years old. Consequently, we used this method to study bronchial hyperresponsiveness in 141 children with asthma and 46 disease controls without asthma or chronic respiratory disorder. The bronchial responsiveness in asthmatic children aged 2 to 5 years was higher than in the disease controls (P less than .001). Further, bronchial responsiveness was significantly higher in moderately as opposed to minimally affected asthmatics (P less than .01), and was gradually higher according to clinical severity. In other age groups as well, the bronchial responsiveness of asthmatic children was higher than of disease controls. There was a close relationship between the level of increased bronchial responsiveness and the clinical severity of asthmatic children. PMID- 3341610 TI - Nitrendipine monotherapy in severe hypertension. AB - Nitrendipine is a new dihydropyridine derivative developed specifically for the treatment of hypertension. Oral nitrendipine was administered to twelve patients with severe hypertension (diastolic blood pressure greater than 114 mm/Hg). All antihypertensive drugs were discontinued at least 72 hours prior to nitrendipine administration. The initial dose of nitrendipine was 5 mgs. orally twice daily which was titrated at 2 to 5 day intervals up to a maximum dose of 40 mgs. twice a day. Average pretreatment blood pressure (+/- SD) was 194/118 (28/3) mm/Hg and was 191/122 (25/9) mm/Hg standing. After 7 to 10 days of nitrendipine monotherapy, the average blood pressure had decreased to 170/102 (20/9) mm/Hg supine and 167/106 (19/8) mm/Hg standing. Thirty days of nitrendipine therapy resulted in a further decrease of average blood pressure to 159/96 (18/7) mm/Hg supine and 154/99 (12/12) mm/Hg standing. Average supine pulse (+/- SD) increased from 79.0 (13.9) to 90 (15.7) beats/min. after 7-10 days and to 82 (17) beats/min. after 30 days of therapy. The average total daily dose of nitrendipine was 47.5 mgs. after 30 days. Side effects were minimal and the medication was well tolerated by most patients. It was concluded that nitrendipine is a potent and effective antihypertensive agent in patients with severe hypertension. PMID- 3341612 TI - Outbreaks of asthma attacks and meteorologic parameters in Bahia Blanca, Argentina. AB - Although Bahia Blanca is a relatively small city, the large daily number of asthmatic patients treated is comparable with cities at least ten times its population. A 1-year study of correlation between the daily cases treated and various meteorologic parameters is presented. Asthmatic outbreaks are normally associated with a dramatic decrease in temperature, humidity, and pressure. This condition may favor the activity of airborne allergenics transported mainly by continental winds. PMID- 3341613 TI - Amiodarone-induced recurrent allergic pneumonitis. AB - Two patients with history of amiodarone-induced pulmonary reactions were accidentally treated again with amiodarone and the pulmonary complication recurred. The clinical symptoms and radiographic findings disappeared after amiodarone was discontinued and the administration of corticosteroids. Recurrent pulmonary reaction from amiodarone on different occasions is a rarely reported complication and confirms the relationship of pulmonary toxicity to chronic amiodarone administration. PMID- 3341614 TI - Incorporation and analysis of ultrasonically nebulized distilled water challenges in an epidemiologic study of asthma and bronchial reactivity. AB - The usefulness of an ultrasonically nebulized distilled water (UNDW) challenge as a screening procedure was tested in an on-going epidemiologic study of asthma and bronchial reactivity. Sixty-six individuals underwent a methacholine challenge, an UNDW challenge, and were administered a standardized respiratory disease questionnaire. To perform the UNDW challenge, subjects inhaled increasing volumes of nebulized distilled water while breathing tidally. Thirty-eight asthmatics, two former asthmatics, 14 normal, and 12 allergic subjects, were included. Sixty six percent of the asthmatics dropped 20% from their baseline FEV1 during the UNDW challenge. Only one allergic or normal subject had a similar drop. The Pearson's correlation coefficient between methacholine and UNDW challenges was 0.60. If positive, an UNDW seems to be highly specific in supporting a diagnosis of asthma, while methacholine challenges are more useful in verifying the presence of non-specific bronchial reactivity. PMID- 3341615 TI - Effectiveness of immunotherapy in patients with mite allergy. PMID- 3341616 TI - President's Address. PMID- 3341617 TI - Asthma, recurrent infections and IgG2 deficiency. PMID- 3341618 TI - A census of airborne mold spores in the atmosphere of the city of Madras, India. AB - A survey of airborne mold spores in the atmosphere of the city of Madras, India was conducted with a Burkard model of the Hirst trap from August 6, 1981 to August 5, 1982. Among the many spore types recorded, spores belonging to Nigrospora, Curvularia, Periconia, Alternaria, Coprinus, Cladosporium, Leptosphaeria, and Torula were common and frequently recorded from the atmosphere. Nigrospora and Cladosporium were most predominant and occurred in large numbers. PMID- 3341620 TI - Prevention of nosocomial pneumonia using topical and parenteral antimicrobial agents. AB - The efficacy of antimicrobial agents applied topically in the oropharynx and trachea with and without intravenous antibiotics in preventing bacterial pneumonias during prolonged (7 to 10 days) mechanical ventilation was studied in 35 baboons, 30 of which had acute lung injury induced by either oleic acid or hyperoxia. In 12 animals receiving no antibiotics, only topical application of polymyxin B (PB), or only intravenous penicillin and gentamicin (IV PCN/GM), moderate or severe pneumonia was found in 81% of lobes examined at necropsy; no lobes were sterile. Pneumonias were polymicrobial in the absence of antibiotics, due to PCN-sensitive organisms in the topical PB group, and due to gram-negative bacilli in the IV PCN/GM group. Combinations of topical PB or GM or both plus IV PCN were highly efficacious in preventing pneumonia in 23 animals as only 15% of the lobes contained moderate to severe pneumonia and 52% of lobes were sterile. In these groups, histologically evident pneumonias were associated with low concentrations of bacteria in lung tissue, principally gram-negative bacilli resistant to the topical agent being used. Resistance to PB appeared to be solely due to selection of intrinsically resistant species, whereas resistance to GM may have developed through additional mechanisms as well. Although this approach to pneumonia prevention is clearly efficacious in this animal model, clinical studies are needed to define the frequency and significance of microbial resistance in human subjects. PMID- 3341619 TI - Bacteriologic diagnosis of nosocomial pneumonia following prolonged mechanical ventilation. AB - Cultures of tracheal secretions, bronchoalveolar lavage (BAL), protected specimen brushes (PSB), and direct lung aspirates were compared with cultures of lung homogenates and histologic findings in 35 baboons after 7 to 10 days of intubation and mechanical ventilation. Six animals received no antibiotics, while the remainder were treated with a variety of prophylactic regimens of intravenous and topical agents. Bacterial contamination at each culture site was expressed as a "bacterial index" (BI), obtained as the sum of the logarithmic concentrations of individual species. In the absence of antibiotics, pneumonias occurred in all animals and were polymicrobial; 56% of organisms in lung tissue were members of the normal upper respiratory tract flora, while 44% were gram-negative bacilli with a mean total bacterial index of 13.94/g. Lobar tissue BI values greater than 6.0/g were found in 77% of lobes containing pneumonias judged by histologic criteria to be moderate or severe in extent, whereas only 7% of lobes with lesser inflammatory changes had similar BI values. The BI values of BAL were linearly related to tissue values, whether the BAL was performed of the same lobe cultured or a different lobe. BAL recovered 74% of all species present in lung tissue compared to 41% by PSB and 56% for needle aspirates. False positive specimens were found with similar frequency with these 3 procedures. Tracheal aspirates revealed 78% of organisms found in lung tissue, but 14 of 35 (40%) of species isolated were not present in lung tissue. BAL provides the best reflection of the lung's bacterial burden, both quantitatively and qualitatively, in the setting of prolonged intubation and ventilation. PMID- 3341621 TI - An alternate method for the determination of functional residual capacity in a plethysmograph. AB - The validity of measuring thoracic gas volume using a single inspiratory effort against an occlusion (Vtginsp) was determined in children and young adults (8 normal control subjects and 17 patients with cystic fibrosis [CF] or asthma). In addition, the validity of the measurement of Vtg at FRC in children at a low panting frequency (Vtgpant) was also determined. During both the panting (encouraged to be about 1 Hz) and inspiratory maneuvers, mouth pressure (Pm) and esophageal pressure (Pes) were measured simultaneously. Hence, Vtgpant and Vtginsp were determined using both delta Pm and delta Pes. Vtginsp using delta Pm was found to be similar to Vtginsp using delta Pes. Values for Vtgpant using either delta Pm or delta Pes were also found to be similar. The percent difference between Vtginsp (using delta Pm) and the average of Vtgpant and Vtginsp (using delta Pes for both) was calculated as an indication of the error of the inspiratory method. The error ranged from -13 to +13% and did not correlate with indices of air-flow limitation or hyperinflation. We have found that Vtginsp can be used to determine FRC in normal children and young adults as well as in those with CF or asthma. In addition, we have also validated the use of Vtgpant at a low panting frequency in these subjects. PMID- 3341622 TI - Thoracic gas volume measurements in chronic obstructive pulmonary disease by low frequency ambient pressure changes. AB - The validity of a new method for measuring thoracic gas volume (Vtg) was studied in 18 bronchitic patients with mild to severe airway obstruction. The method entailed submitting the subject to very slow sinusoidal variations of ambient pressure (delta Pam) and studying the relationship between delta Pam and the resulting gas displacement at the mouth (delta Vaw): Vtgapc = PB.delta Vaw/delta Pam.cos phi, where PB is barometric minus alveolar water vapor pressure, and phi is the phase angle between Pam and Vaw. delta Pam of 40 cm H2O at 0.05 Hz were achieved by placing the subject in a 410-I body chamber connected to a large stroke volume reciprocating pump. Pam and Vaw were processed digitally by Fourier transform to obtain their amplitude ratio and phase angle at the frequency of interest. Vtg was also measured by body plethysmography (Vtgplet) during slow panting maneuvers (0.79 +/- 0.19 Hz) and also in order to detect any artifactual frequency dependence at a higher panting frequency (1.71 +/- 0.27 Hz); the agreement between the 2 estimates in all subjects (r = 0.975) suggested that Vtgplet could be taken as a valid reference. Functional residual capacities derived from Vtgapc and Vtgplet were not significantly different (5.113 +/- 1.198 versus 5.260 +/- 1.328 L) and were highly correlated (r = 0.915). Intermethod differences averaged 1.7 +/- 10.5% and were not significantly correlated to functional indices. We conclude that the new method provides accurate Vtg values in patients with chronic airway obstruction. PMID- 3341623 TI - Cumulative and reversible effects of lifetime smoking on simple tests of lung function in adults. AB - Data from a random sample of 8,191 men and women from 6 U.S. cities are used to fit a model describing the effects of cumulative and current cigarette smoking on pulmonary function. The data show that smokers suffer an irreversible loss of FVC and FEV1, which is described by a linear function of their cumulative cigarette smoking as measured in pack-years. For a typical male 173 cm tall, the estimated loss of FEV1 is 7.4 ml for each pack-year smoked. For a typical woman, 161 cm tall, the estimated effect is 4.4 ml per pack-year. Current cigarette smoking adds an acute deficit over and above the cumulative effect of lifetime smoking. For any lifetime pack-years, exsmokers have higher levels of FEV1, 123 ml for a typical man, 107 ml for a typical woman, than do current smokers of a pack per day (p less than 0.001). A man who starts smoking one pack of cigarettes per day at 25 yr of age would at age 60, after 35 pack-years of exposure, have an expected FEV1 equal to that of a man 69.4 yr of age who had never smoked. If he stopped smoking at 60 yr of age, his expected level would increase to that of a 66.5-yr-old never-smoker. This model therefore estimates how much lung function is irreversibly lost by smoking, estimates how much could be regained with cessation of smoking, and predicts the future loss of lung function in both cases. PMID- 3341624 TI - Does the single-breath N2 test identify the smoker who will develop chronic airflow limitation? AB - We report here the results of a 9- to 11-yr follow-up of 2 cohorts in which spirometry and the single-breath N2 test were used throughout the follow-up period to determine the usefulness of the single-breath N2 test in identifying the smoker who is experiencing a rapid decline in FEV1 and is therefore likely to be at risk of developing chronic airflow limitation. The analyses are based on 734 subjects tested from 3 to 5 times over the follow-up period; 82 smokers developed an abnormal FEV1 during the follow-up period. Of these, 71 (87%) had had an abnormal single-breath N2 test at some time prior to the FEV1 becoming abnormal. Of the single-breath N2 test variables, CC/TLC was the only one significantly associated with the rate of decline of FEV1 in both cohorts once adjustments were made for age, sex, height, and smoking. We conclude that the single-breath N2 test can be useful in identifying the smoker who is at risk of developing chronic airflow limitation. However, its usefulness is diminished by the high proportion of smokers who have mild functional abnormalities but do not progress to develop chronic airflow limitation. We also find that the single breath N2 test does not appear to have a useful predictive value in nonsmokers. PMID- 3341625 TI - Effects of ambient ozone on respiratory function in active, normal children. AB - Respiratory functions were measured on a daily basis by spirometry over a period of 4 wk at a summer camp at Fairview Lake in northwestern New Jersey. Fifty-three boys and 38 girls 8 to 15 yr of age participated in the study on at least 7 days; 37 children were in residence for 4 wk, 34 for the first 2 wk only; and 20 for the last 2 wk. There were 72 whites, 15 blacks, 3 Asians, and 1 Hispanic in the study group. Multiple regression analyses indicated that the O3 concentration in the previous hour, the cumulative daily O3 exposure during the hours between 9 A.M. and the function measurement, ambient temperature, and humidity were the most explanatory environmental variables for daily variations in function, with the 1 - h O3 concentration having the strongest influence. Linear regressions were performed for each child between O3 concentration and function, and all average slopes were significantly negative (p less than 0.05) for FVC, FEV1, PEFR, and FEF25-75 for all children, and for boys and girls separately. Comparable results were obtained in data subsets (i.e., children studied during the first or second 2 wk only, and for data sets truncated at O3 less than 80 and O3 less than 60 ppb). The average regression slopes (+/- SE) for FVC and FEV1, respectively, were -1.03 +/- 0.24 and -1.42 +/- 0.17 ml/ppb, whereas for PEFR and FEF25-75 they were -6.78 +/- 0.73 and -2.48 +/- 0.26 ml/s/ppb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341626 TI - Ethane production rate in rats exposed to high oxygen concentration. AB - Production rates for ethane gas, a hydrocarbon byproduct of lipid peroxidation, measured from the ethane present in the exhaled breath of rats, were used to determine changes in oxygen-free radical activity. Rates of ethane production were measured in rats housed in metabolic chambers and exposed to room air and to high oxygen concentrations. Expired ethane, adsorbed onto activated charcoal and then liberated by heating, was measured by gas chromatography. Ethane production rates in groups of 8 rats increased during 8 h of 100% oxygen exposure from a mean (+/- SE) room air value of 11.30 +/- 1.15 to 27.85 +/- 2.93 pmol/min/100 g rat (p less than 0.005). The mean (+/- SE) percent increases in ethane production after exposure to 100% oxygen in 8 rats pretreated with 0.1 mg/100 g of vitamin E in corn oil vehicle (0.1 ml/100 g) injected intraperitoneally and in a group of 5 rats injected with vehicle alone averaged 157.16 +/- 37.83% and 150.98 +/- 25.19%, respectively. The percent changes noted were not significantly different as measured by analysis of variance. These data indicate that lipid peroxidative activity, hence oxygen-free radical activity, increases in normally fed rats exposed to hyperoxia at a time prior to the previously reported neutrophil influx into the lungs of similarly exposed rats and that it is not attenuated by pretreatment with vitamin E. PMID- 3341629 TI - CT measurements of lung density in life can quantitate distal airspace enlargement--an essential defining feature of human emphysema. AB - We used a computerized microscopic image analysis system to directly measure the surface area of distal air spaces in methacrylate-embedded blocks randomly selected from inflation-fixed lobes that were resected from 45 patients as treatment of their peripheral lung tumors. In 28 of these patients, a preoperative computer tomography (CT) scan, at 6 and 10 cm below the sternal notch, was used to generate frequency histograms of CT numbers (measured as EMI units), a measure of lung density, in pixels from the lung or lobe that was subsequently resected. A similar CT number histogram was also derived from the lateral two fifths of the area of lobe/lung that was to be resected. The EMI unit that defined the lowest fifth percentile of this latter histogram correlated (n = 28, r = -0.77, p less than 0.001) with the mean value of the surface area of the walls of distal airspaces per unit lung volume (AWUV) in the five 1 mm x 1 mm microscopic fields with the lowest AWUV values, out of the 20 to 35 such fields examined in each patient. In the 34 of the 45 patients in whom we also measured volume-corrected diffusing capacity (DLCO/VA), this also correlated (n = 34, r = 0.84, p less than 0.001) with this value of AWUV, which measures the surface area of airspaces distal to the terminal bronchioles--reflecting an increase in airspace size, a defining characteristic of emphysema. However, a low DLCO/VA is nonspecific, whereas an abnormally low regional lung density is more likely to be specific for emphysema. In addition, highlighting those pixels of the CT display with low CT numbers (i.e., EMI units -500 [air] to -450, where zero = water) can locate areas of macroscopic emphysema, as shown by subsequent pathologic examination. Thus the quantitative CT scan can diagnose, quantitate, and locate mild to moderate emphysema, in humans, in life, noninvasively. PMID- 3341628 TI - Nitrogen-dioxide-induced emphysema in rats. Lack of worsening by beta aminopropionitrile treatment. AB - We evaluated the effect of beta-aminopropionitrile (beta APN) on the nitrogen dioxide (NO2) animal model of emphysema. Rats maintained on a beta APN supplemented or a regular diet were exposed to 30 ppm NO2 for intervals ranging from 1 to 8 wk. Emphysema development was assessed by histologic evaluation and by changes in lung volume and mean linear intercept values. Evidence of pathologic changes were also documented by clinical and radiographic findings of osteolathyrism. The induction of centriacinar emphysema was attributed specifically to NO2 exposure. Neither the severity of the emphysema nor the time course of its development was altered by the beta APN-supplemented diet. These findings are in marked contrast to those observed with the exogenous elastase model of the disease, and they suggest that elastin synthesis and repair may not modulate elastin destruction in the NO2 model of emphysema. PMID- 3341627 TI - Antigenic analysis of household dust samples. AB - Household dust samples from the homes of 106 allergy clinic patients in Baltimore were analyzed for specific allergen content. Dust mite antigen content was determined by enzyme-linked immunosorbent assays (ELISA) specific for the major allergens of Dermatophagoides pteronyssinus, D. farinae, and D. microceras. Cat and dog antigen content were determined by ELISA using antisera for Fel d 1 (formerly cat allergen 1) and dog allergens 3 and 13, respectively. Mold content was assessed by culture with microscopic identification. Dust mite antigen was detected in 99% of homes (D. farinae, 95%; D. pteronyssinus, 88%; D. microceras, 31%), with total antigen content ranging from 50 ng/g dust (the lower limit of detection) to 30,170 ng/g (median, 1,123 ng/g). Animal allergens were found in 100% of samples (cat: range, 2 to 130,000 ng Fel d 1/g; median, 90 ng/g; dog: range, 112.5 to 585,000 IU/g; median, 2,719.5 IU/g). Although there were highly significant differences in antigen content (p less than 0.001) between homes with and without a particular pet in residence, many homes without pets contained pet allergens at high concentrations. Molds were also detected in 100% of homes (range, 4 to 761 colonies/30 mg dust; median, 72 colonies/30 mg). No correlation was demonstrated between antigen content and skin test results, a history of asthma, symptoms on allergen exposure, or the age of the home (except for molds) for any of the allergens detected. We conclude that dust mite allergens, cat and dog allergens, and molds are virtually ubiquitous in Baltimore homes and that our ability to predict the presence and relative quantities of these allergens on clinical grounds is very limited. PMID- 3341630 TI - Magnetic resonance imaging and computerized tomography in central hypoventilation. AB - Central hypoventilation syndrome (CHS) is a disorder of respiratory control. It may be an idiopathic primary disease or it may be the secondary consequence of an infectious process or Chiari II malformation. Clinical data suggest that the primary defect involves the brainstem respiratory centers. To date, pathologic evaluation has linked primary CHS with decreased density of neurons and myelinated nerve fibers in the medulla and brainstem gliosis, and absence of the external arcuate nucleus. Magnetic resonance imaging (MRI) is now considered the most reliable imaging technique for evaluating the brainstem. In the hope of finding gross structural abnormalities that might correlate with the clinical and pathologic features of CHS, we used MRI and computerized tomography (CT) to evaluate the brain, brainstem, and spinal cord of 17 infants and children with central hypoventilation (11 primary, 6 secondary). Each of the 11 children with primary CHS demonstrated a normal brainstem and spinal cord by MRI. However, 9 of 11 infants had mild ventricular dilatation and modest prominence of the sulci interpreted as either mild atrophy or mild extraventricular obstructive hydrocephalus. Results of studies in the one child with postinfectious disease were normal. The 5 infants with Chiari II malformation demonstrated characteristic brainstem changes. MRI results modified clinical care, resulting in symptomatic improvement after hindbrain decompression by cervical laminectomy in 1 infant and surgical drainage of syringobulbia in 1 child. In summary, in primary CHS, the MRI and CT provided evidence for a more diffuse CNS process rather than a specific brainstem lesion. Such a lesion may be too small or too subtle to resolve with MRI or CT. In secondary central hypoventilation, MRI modified surgical management in 2 cases, resulting in symptomatic improvement of hypoventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341631 TI - Role of plasminogen activator in degradation of extracellular matrix protein by live human alveolar macrophages. AB - Recent evidence indicates that human alveolar macrophages can degrade purified elastin in vitro by a cell contact-dependent process involving acidic proteinases of the cysteine proteinase class. It is unclear to what extent these cells can degrade elastin within a natural extracellular matrix. To address this question, we cultured live human alveolar macrophages on elastin-rich, 3H-lysine-labeled, extracellular matrices deposited by rat smooth muscle cells in vitro. Under various culture conditions, we then measured release of total radioactivity from the matrices during co-culture with cells as well as net loss of desmosine/isodesmosine as a specific marker of elastin degradation. Live macrophages adhered to and progressively solubilized matrix protein at a slow rate (approximately 5 micrograms/10(6) cells/24 h) but the rate of solubilization increased more than 15-fold in the presence of plasminogen. The elastin component of the complicated matrix was not measurably degraded in the absence of plasminogen, but in medium containing plasminogen, 3.5 X 10(6) macrophages degraded 25 +/- 8 micrograms of elastin in 72 h. After pretreatment of matrices with trypsin to remove glycoprotein elements, live cells degraded 16 +/- 4 micrograms of elastin under plasminogen-free conditions. The addition of serum to the medium (1 to 5%) inhibited degradation of elastin within whole matrices (approximately 50% compared to serum-free medium containing plasminogen) but had no effect on degradation of elastin in trypsin-pretreated matrices. An active site inhibitor of cysteine proteinases, Z-phenylalanine-phenylalanine diazomethylketone, blocked approximately 50% of the elastin degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341633 TI - Airway epithelial damage in premature infants with respiratory failure. AB - To evaluate the evolution of airway epithelial damage in premature infants developing bronchopulmonary dysplasia (BPD), a detailed quantitative light and electron microscopic evaluation was performed of the major airways in 3 infants who succumbed from respiratory failure. The 3 infants ranged from 24 to 28 wk gestational age and died after 14 h, 10 days, and 6 months of life. The tracheal epithelium was severely damaged with up to half of the epithelium being denuded in each infant. The infants who died after 14 h and after 10 days demonstrated minimal epithelial denudation in more distal bronchial divisions. However, gross and microscopic abnormalities of the ciliated component of the epithelium were common. In the infant with severe established BPD, there was extensive epithelial denudation and ciliary abnormalities out to the fourth bronchial division. The percentage of goblet cells in the total cell population decreased from proximal to distal major airways, with the lowest percentage being seen in the infant with established BPD. These studies demonstrate the respiratory failure and assisted ventilation in the human neonate is associated with severe epithelial damage in the trachea and proximal bronchi. It suggests that the difficulty in clearing airway secretion results from a defect in mucociliary transport system rather than from an increase in airway secretion. PMID- 3341634 TI - Acute myopathy in severe acute asthma treated with intravenously administered corticosteroids. AB - An association between the use of parenteral corticosteroids in acute asthma and the development of an acute myopathy was first reported in 1977. We report 2 further cases that contribute significantly to our knowledge of this rare complication of the treatment of acute asthma. These cases demonstrate that the acute myopathy is not just a complication of the use of parenteral hydrocortisone in patients requiring ventilatory support during an episode of acute asthma. The acute myopathy can occur with several parenteral corticosteroids, may be severe (with rhabdomyolysis and myoglobinuria), and may have protracted morbidity. Prospective follow-up allowed demonstration of histopathology, electrophysiology, and also the contribution of various pharmacologic agents. Careful analysis of the evidence strongly implicates corticosteroids as the causative agent. PMID- 3341632 TI - Ozone-induced augmentation of eicosanoid metabolism in epithelial cells from bovine trachea. AB - Epithelial injury and inflammation have been implicated in ozone-induced airway hyperresponsiveness. Because ozone is relatively insoluble and highly reactive, toxicologic effects of this compound may be limited to the plasma membranes of airway epithelium. We hypothesize that oxidant damage to epithelium may result in elaboration of various eicosanoids, which are known to alter airway smooth muscle responsiveness and epithelial cell functions (including ion transport). To examine eicosanoid metabolism after exposure to 0.1 to 10.0 ppm ozone, epithelial cells derived from bovine trachea were isolated and grown to confluency. Bovine tracheal cells in culture expressed differentiated features characteristic of epithelial cells, including a plasma membrane with a specialized polar morphology, an extensive network of filaments that were connected through intercellular junctional complexes, and keratin-containing monofilaments as determined by indirect immunofluorescent localization. Monolayers were alternately exposed to ozone and culture medium for 2 h in a specially designed in vitro chamber using a rotating inclined platform. Eicosanoid products were measured by the release of [3H]-labeled products from cells incubated with [3H] arachidonic acid for 24 h before exposure and by the release of immunoreactive products into the cell supernatant. Both methods revealed ozone-induced increases in cyclooxygenase and lipoxygenase product formation with significant increases in prostaglandins E2, F2 alpha, 6-keto F1 alpha, and leukotriene B4. Release rates of immunoreactive products were dose-dependent, and ozone concentrations as low as 0.1 ppm produced an increase in prostaglandin F2 alpha. These findings are consistent with the hypothesis that ozone can augment eicosanoid metabolism in airway epithelial cells. PMID- 3341636 TI - The potential for conflict of interest of members of the American Thoracic Society. PMID- 3341635 TI - Lack of radiographic evidence of interstitial pulmonary edema after maximal exercise in normal subjects. AB - Recent physiologic studies have indirectly suggested that interstitial pulmonary edema may develop at maximal exercise in normal humans at sea level. Therefore, we compared chest radiographs taken before and immediately after incremental exercise to maximum in 5 healthy young subjects. We looked for evidence of redistribution of pulmonary blood flow, pulmonary venous distension, loss of sharp definition of pulmonary vascular markings, hilar blurring, Kerley's A, B, or C lines, peribronchial or perivascular cuffing, widening of fissures, pleural effusion, and diffuse opacity. We also quantitated radiographic density in 6 areas of the film in each subject. There was no radiographic change to suggest an increase in lung water in any lung zone in any of the subjects. Given the documented sensitivity of chest radiography in this respect, we conclude that any increase in extravascular lung water during exercise must be trivial. PMID- 3341637 TI - Critical care and iatroepidemics. PMID- 3341638 TI - Extreme dyspnea from unilateral pulmonary venous obstruction. PMID- 3341639 TI - Cold facial stimulation reduces breathlessness induced in normal subjects. PMID- 3341640 TI - The high cost of acute health care: a review of escalating costs and limitations of such exposure in intensive care units. PMID- 3341641 TI - Standardization of spirometry. PMID- 3341642 TI - Results of experimental endoscopic esophageal varix ligation. AB - Endoscopic Variceal ligation (EVL) is performed using a flexible gastroscope and a recently developed elastic band ligating device. Varices from 3-5 mm in diameter were created in a canine model. Thirty seven variceal sites underwent EVL with successful ligation on first attempt in 34 (92%). Gross and microscopic examination of treated sites at 1-60 days showed ischemic necrosis of mucosa and submucosa (24 hours), acute inflammation, demarcation of viable and necrotic tissue, and appearance of granulation tissue (3-7 days), full thickness replacement of mucosa and submucosa with maturing scar tissue and near complete re-epithelialization (14-21 days), and complete healing (50-60 days). Inflammation and scar tissue deposition consistently obliterated submucosal venous channels but left muscularis propria intact. No perforations or other adverse clinical or histological effects were observed. EVL treatment of canine esophageal varices appears to result in safe and effective obliteration of vascular channels in the submucosa by a process of inflammation and scar formation. PMID- 3341643 TI - The effect of an intragastric balloon on weight loss, gastric acid secretion, and serum peptide levels. AB - The results of our preliminary experience with the gastric balloon program for weight loss in morbidly obese patients are reported. In a pilot project, we measured gastric-acid secretion, gastrin and cholecystokinin (CCK) levels in ten patients before and during balloon therapy in a study of the impact of the balloon on gastric physiology. Gastric-acid secretion tended to decrease following balloon treatment, while gastrin and CCK levels were unchanged suggesting that weight loss is achieved by mechanisms, which are not mediated by gastrin or CCK. The balloon program was then expanded to a group of 29 patients who met the criteria. They were followed for a period of 4 months. Average weight loss for the group was 31 +/- 4 pounds for a monthly average of 8 pounds. The main complications were gastric ulcers in four patients and a small-bowel obstruction in one patient. Satisfactory weight loss was achieved in 80 per cent of patients, but this benefit must be balanced against a relatively high incidence (17%) of side effects, some of which were quite serious. Therefore, the gastric balloon program should still be considered experimental. PMID- 3341644 TI - Is preoperative colonoscopy necessary in carcinoma of the colon and rectum? AB - The incidence of synchronous polyps of the colon has been shown to be 25 to 40 per cent and the incidence of synchronous carcinomas to be two to eight per cent. Because of this, many surgical groups now advocate routine preoperative colonoscopy on all patients with colon carcinoma. The possibility of spreading and implanting tumor cells with the colonoscope has prompted the authors to purposely avoid preoperative colonoscopy and then clear the colon of any missed lesions with an early postoperative colonoscopy. This study is a retrospective review of 104 patients who have undergone a partial colectomy for colon and rectal carcinoma followed by a postoperative colonoscopy between June 1982 and June 1986. The purpose is to determine the adequacy of intraoperative palpation to detect synchronous neoplasms, and to further define the role of perioperative colonoscopy. The results of 34 per cent synchronous polyps and 5.8 per cent synchronous carcinomas parallels previous studies. The six patients with synchronous carcinomas were discovered by intraoperative palpation and the operation was modified in four of the six patients. Postoperative colonoscopy revealed polyps in 20 per cent of the patients, but all of these were amenable to snare polypectomy or electrocoagulation. No carcinomas were overlooked by palpation. It is our conclusion that intraoperative palpation is adequate for detection of synchronous carcinomas and therefore the risk and expense of preoperative colonoscopy can be avoided. Early postoperative colonoscopy, however, is imperative to clear the colon of small polyps which have the potential to progress to carcinoma. PMID- 3341645 TI - Complications in colonoscopic polypectomy: lessons to learn from an experience with 1576 polyps. AB - One thousand five hundred and seventy six polyps were removed from 1190 patients. Polyp size ranged from 5 mm to 6 cm. Nineteen complications occurred, an incidence of 1.2 per cent. Bleeding was the most common complication, accounting for 53 per cent of all complications, followed by transmural burn (32%). Other complications included a "silent" free perforation, a snare-wire entrapment, and an ensnared bowel wall. Certain complications can be prevented provided the basic safety features are observed. Some complications require conservative management, others require an operation. PMID- 3341646 TI - Evaluation of endoscopy training in a general surgery residency. AB - To evaluate the gastrointestinal endoscopy training program, a survey of the 33 former chief residents, who finished our program in 1981-1986, was conducted. All 33 graduates responded; 22 graduates are general surgeons, 11 completed or are completing training in a surgical specialty. Eighteen of the 22 general surgeons routinely perform endoscopy in their practice. Graduates in cities with a population greater than 250,000 are as likely to perform endoscopy as the surgeons who live in smaller communities. Ninety one per cent consider endoscopy training to have been an important part of their surgical training. Based on this assessment, endoscopy training is an important part of a general-surgery residency. PMID- 3341647 TI - Endoscopic and histologic correlates of intestinal ischemia in a canine model. AB - The purpose of this study was to correlate endoscopic, microscopic and gross changes in an isolated ischemic segment of canine jejunum. Three experiments were devised. The arterial and venous blood supply to a 20 cm segment of distal jejunum in mongrel dogs was isolated and the bowel divided. External and endoscopic photography and intestinal biopsies were obtained at 0, 5, 15, 30, 60, 120, 180 and 360 minutes after vascular occlusion. Arterial occlusion was characterized by initial blanching of the mucosa, hyperperistalsis, edema, spasm and serosal pallor within 5 minutes. Microscopically, capillaries became congested at 5 minutes; epithelial sloughing occurred in 1-2 hours; necrosis of the tips of the villi occurred at 4 hours; and necrosis of muscle fibers was observed at 18 hours. Venous occlusion was characterized by marked mucosal and edema and hemorrhages within 5 minutes. At 15 minutes serosal hemorrhages were observed. Mucosal sloughing with hemorrhage and infarction were observed at 3 hours. Microscopically, mucosal capillary congestion was severe at 5 minutes and widespread hemorrhages were seen at 15 minutes. Mucosal sloughing began at 30 minutes and was severe by 60 minutes. Complete mucosal necrosis occurred by 3 hours. Combined arterial and venous occlusion was similar to arterial occlusion alone except for the early appearance of punctate mucosal hemorrhages. Massive submucosal hemorrhages did not occur. Results demonstrate that arterial and venous occlusion can be differentiated endoscopically; venous occlusion appears to be more readily injurious; and endoscopy and biopsy are valuable in diagnosis and management. PMID- 3341648 TI - Current generation video endoscopes. A critical evaluation. AB - Video endoscopy is the latest technical advance in the observation of the gastrointestinal tract. In 2 years, three video endoscope systems have emerged to develop the field of digital imaging. In order to accurately assess the rapidly changing technology, these state of the art systems were "bench" tested in an electronics laboratory to objectively compare resolution, brightness (luminosity), color intensity (chroma), and field of view. All systems were excellent, surpassing the professional broadcasting minimum standards for the adequate discrimination of objects and colors. The Welch Allyn Video-Endoscope originated video endoscopy continued to demonstrate a superior resolution; however this was at the expense of a significantly more narrow field of view, relative to the two newer systems. Although all systems have adequate luminosity and chroma, there were differences in the maximum amounts of luminosity and chroma. This is reflected in the observation that the most recently introduced system, Olympus Endoscopic Video Information System had relatively low levels of light beyond 9 cm from the tip, while the other systems had ample illumination. This report on the relative advantages of each system is based on the interpretations, implications, and practical applications of these findings. PMID- 3341649 TI - Gastric mucosal dissection using the Nd-YAG laser synthetic sapphire crystal contact probe. Development of an endoscopic method for the treatment of pancreatic pseudocysts. AB - A canine gastric-ulcer model was developed to evaluate the safety and effectiveness of the neodymium yttrium-aluminum-garnet (Nd-YAG) laser synthetic sapphire crystal contact probe in intraluminal gastric dissection. The purpose of the study was to assess the potential endoscopic application of the Nd-YAG contact probe in cystogastrostomy for the treatment of selected patients with pancreatic pseudocyst. Seven dogs were used in the study. In the first two dogs, full-thickness linear incisions through the gastric wall demonstrated the Nd-YAG contact probe could be used for a full-thickness gastrostomy dissection. In the other five dogs, gastric ulcers were created by injection of morrhuate sodium (5%). Gastric mucosal dissection with the Nd-YAG contact probe was performed without difficulty. Hemostasis was obtained with either the Nd-YAG contact probe or noncontact fiber, and all areas of dissection and ulcer beds healed within 35 days. The Nd-YAG laser contact endoscopic delivery system appears to be a promising technique for intraluminal dissection. PMID- 3341650 TI - Angina and exertional myocardial ischemia in diabetic and nondiabetic patients: assessment by exercise thallium scintigraphy. AB - Patients with diabetes mellitus and coronary artery disease are thought to have painless myocardial ischemia more often than patients without diabetes. We studied 50 consecutive patients with diabetes and 50 consecutive patients without diabetes, all with ischemia, on exercise thallium scintigraphy to show the reliability of angina as a marker for exertional ischemia. The two groups had similar clinical characteristics, treadmill test results, and extent of infarction and ischemia, but only 14 [corrected] patients with diabetes compared with 34 [corrected] patients without diabetes had angina during exertional ischemia. In diabetic patients the extent of retinopathy, nephropathy, or peripheral neuropathy was similar in patients with and without angina. Angina is an unreliable index of myocardial ischemia in diabetic patients with coronary artery disease. Given the increased cardiac morbidity and mortality in such patients, periodic objective assessments of the extent of ischemia are warranted. PMID- 3341651 TI - Antibodies to vasopressin in patients with diabetes insipidus. Implications for diagnosis and therapy. AB - STUDY OBJECTIVE: To determine whether antibodies to vasopressin play a role in the development of diabetes insipidus or interfere with diagnosis and treatment. DESIGN: Random plasma or serum samples for determining of antibodies to vasopressin were collected from patients and controls. SETTING: Referral university hospital with most patients studied in the clinical research center. PATIENTS: Twenty-nine healthy controls and 113 patients with polyuria (15 with primary polydipsia; 86 with neurogenic diabetes insipidus [60 studied before, 28 during, and 10 after antidiuretic hormone treatment]; and 12 with nephrogenic diabetes insipidus). INTERVENTIONS: Antibodies were detected by incubating samples with radiolabeled 125I-arginine vasopressin. The effect of antibodies on diagnosis was studied by examining the relation of plasma vasopressin to osmolality measured during dehydration or infusion of hypertonic saline and the relation of urine osmolality to plasma vasopressin measured during dehydration. MEASUREMENTS AND MAIN RESULTS: Antibodies to vasopressin were not detected in patients with primary polydipsia, nephrogenic diabetes insipidus, or neurogenic diabetes insipidus studied before therapy with antidiuretic hormone. Antibodies were detected in 6 of 28 patients studied during such treatments. All 6 patients reported decreased antidiuretic response to previously effective therapy with arginine or lysine vasopressin but had normal response to desmopressin or chlorpropamide. CONCLUSION: Diabetes insipidus does not result from spontaneously occurring antibodies to vasopressin. The antibodies occasionally develop during treatment with antidiuretic hormone and, when they do, almost always result in secondary resistance to its antidiuretic effect. Antibodies usually do not impair the response to other forms of therapy; they only rarely interfere with the diagnosis of diabetes insipidus, by falsely suggesting the presence of the partial nephrogenic form. PMID- 3341652 TI - Drug purpura due to surreptitious quinidine intake. AB - Three patients had recurrent episodes of thrombocytopenia that resembled drug purpura, but the drug history in each case did not support the diagnosis. Although the patients specifically denied taking quinidine, serologic testing with this drug was done because the patients had access to it, and it is the commonest cause of drug purpura. Highly specific quinidine-dependent antiplatelet antibodies were found in the sera of all three patients. After being informed of the laboratory findings, the patients have had no recurrences of purpura. Serologic tests for quinidine- or quinine-dependent antibodies can help elucidate some obscure cases of purpura that may be self-induced. PMID- 3341654 TI - Standardization of spirometry: a summary of recommendations from the American Thoracic Society. The 1987 update. AB - The spirometer is used to measure forced vital capacity in pulmonary, occupational, and general medicine. Results of spirometry affect decisions regarding patient treatment and disability compensation. Accurate spirometers are also required for epidemiologic studies. The recommendations of the American Thoracic Society cover equipment selection, validation, and quality control; maneuver performance recommendations; measurement procedures; and reference values and interpretation standardization. PMID- 3341653 TI - Metoclopramide-induced agranulocytosis. PMID- 3341655 TI - Uniform requirements for manuscripts submitted to biomedical journals. International Committee of Medical Journal Editors. PMID- 3341656 TI - Guidelines for statistical reporting in articles for medical journals. Amplifications and explanations. AB - The 1988 edition of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals includes guidelines for presenting statistical aspects of scientific research. The guidelines are intended to aid authors in reporting the statistical aspects of their work in ways that are clear and helpful to readers. We examine these guidelines for statistics using 15 numbered statements. Although the information presented relates to manuscript preparation, it will also help investigators in earlier stages make critical decisions about research approaches and protocols. PMID- 3341657 TI - Stopping antibiotic therapy in neutropenic patients. AB - Infection is the major cause of death in neutropenic patients. Because of the lack of acute inflammatory cells, the usual signs of infection are often absent in these patients. Therefore, unexplained fever in a neutropenic patient requires prompt initiation of antibiotic therapy. Many physicians advocate continuing antibiotic therapy until neutropenia resolves. However, prolonged treatment with broad-spectrum antibiotics increases the risks of drug toxicity and superinfection with resistant bacteria and fungi. Based on a critical review of the literature and a large personal clinical experience, I offer tentative guidelines for withdrawing antibiotic therapy in persistently neutropenic patients. When antibiotic therapy is discontinued, frequent and careful monitoring of these patients and a low threshold for reinstituting antibiotic therapy are essential. PMID- 3341658 TI - Bone densitometry and clinical decision-making in osteoporosis. PMID- 3341659 TI - Confidence intervals extract clinically useful information from data. PMID- 3341660 TI - Uniform requirements for manuscripts: the new, third edition. PMID- 3341661 TI - Clinical competence in percutaneous renal biopsy. Health and Public Policy Committee. American College of Physicians. PMID- 3341663 TI - Alternate methods of heparin administration. PMID- 3341662 TI - Nifedipine, hypotension, and myocardial injury. PMID- 3341664 TI - Aminophylline and chronic obstructive pulmonary disease. PMID- 3341665 TI - Hodgkin disease and infection with the human immunodeficiency virus (HIV) in Italy. PMID- 3341666 TI - Cerebellar disease without dementia and infection with the human immunodeficiency virus (HIV) PMID- 3341667 TI - Bicarbonate therapy in severe acidosis. PMID- 3341668 TI - Low-dose acyclovir and acute renal failure. PMID- 3341669 TI - Potential neurotoxicity of tryptophan. PMID- 3341670 TI - Cholesterol reduction and life expectancy. PMID- 3341671 TI - Pleural fluid pH in malignant effusions. Diagnostic, prognostic, and therapeutic implications. AB - STUDY OBJECTIVE: To determine whether the measurement of pleural fluid pH in malignant effusions has diagnostic use, predicts survival, and has therapeutic implications. DESIGN: A prospective comparison of cytologic examinations and pleural biopsy results, survival, and response to chemical pleurodesis with tetracycline in patients with normal-pH (7.30 or greater) and low-pH (less than 7.30) malignant pleural effusions. SETTING: Academic medical center, university referral hospital, city hospital, and Veterans Administration hospital. PATIENTS: Sixty patients with malignant pleural effusions, proven at either initial thoracentesis by cytologic examination or within 4 months of initial thoracentesis by repeat thoracentesis, thoracotomy, or autopsy, were followed until death. INTERVENTION: Twenty-one patients, 12 with normal pleural fluid pH and 9 with low pleural fluid pH, were treated with tube thoracostomy and intrapleural tetracycline for symptomatic, recurrent pleural effusions. MAIN RESULTS: The 20 patients with low-pH malignant effusions had a significantly greater positivity on initial pleural fluid cytologic evaluation, a shorter mean survival, and a poorer response to tetracycline pleurodesis compared with 40 patients with normal-pH malignant effusions. CONCLUSIONS: Determination of pleural fluid pH in malignant effusions provides a rational approach to further diagnostic testing, prognostic information, and a rationale for palliative treatment. PMID- 3341672 TI - Postmenopausal estrogen use and coronary atherosclerosis. AB - STUDY OBJECTIVE: To determine whether estrogen replacement therapy affects the prevalence of severely obstructive coronary arterial lesions defined by selective coronary arteriography. DESIGN: Case-control study. SETTING: Large, urban, university-affiliated referral hospital. PATIENTS: From a consecutive sample of 6452 women having coronary arteriography between 1972 and 1984, 2188 patients were eligible for study; others were excluded because they were nonmenopausal, had congenital heart defects, valvular heart disorders, primary myocardial disease, or no more than mild to moderate coronary artery disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hospital nurses routinely obtained medication histories. Staff invasive cardiologists interpreted coronary arteriograms. Clinical, laboratory, and angiographic data were abstracted from the cardiac catheterization reports and entered into a computerized registry. Postmenopausal estrogen use for 1444 cases of coronary artery disease (70% stenosis) was compared to that 744 controls (0% stenosis). The odds ratio estimate of the risk of coronary artery disease for estrogen users relative to the risk of coronary artery disease for nonusers was 0.44 (95% confidence interval, 0.29 to 0.67) after adjustment for age, cigarette smoking, diabetes, cholesterol, and hypertension. Postmenopausal estrogen replacement was a significant independent protective factor for coronary artery disease in a multivariate logistic regression model (P = 0.037). CONCLUSION: The data suggest that postmenopausal estrogen treatment reduces the risk for angiographically significant coronary artery disease. PMID- 3341673 TI - Botulism from chopped garlic: delayed recognition of a major outbreak. AB - Diagnosis of botulism in two teenaged sisters in Montreal led to the identification of 36 previously unrecognized cases of type B botulism in persons who had eaten at a restaurant in Vancouver, British Columbia, during the preceding 6 weeks. A case-control study implicated a new vehicle for botulism, commercial chopped garlic in soybean oil (P less than 10(-4)). Relatively mild and slowly progressive illness, dispersion of patients over at least eight provinces and states in three countries, and a previously unsuspected vehicle had contributed to prolonged misdiagnoses, including myasthenia gravis (six patients), psychiatric disorders (four), stroke (three), and others. Ethnic background influenced severity of illness: 60% of Chinese patients but only 4% of others needed mechanical ventilation (P less than 10(-3]. Trypsinization of serum was needed to show toxemia in one patient. Electromyography results with high frequency repetitive stimulation corroborated the diagnosis of botulism up to 2 months after onset. Although botulism is a life-threatening disease, misdiagnosis may be common and large outbreaks can escape recognition completely. PMID- 3341674 TI - Mechanism of aortic balloon valvuloplasty: fracture of valvular calcific deposits. AB - Balloon valvuloplasty has been shown to acutely reduce the hemodynamic and symptomatic severity of calcific aortic stenosis. The mechanism by which this improvement is accomplished is not known. At necropsy, three patients who died after hemodynamically successful aortic balloon valvuloplasty were found to have aortic valve calcific deposits fractured at one or more sites. These findings suggest that fracture of leaflet calcium represents the basis for successful aortic balloon valvuloplasty. PMID- 3341675 TI - Serologic markers with fulminant hepatitis in persons positive for hepatitis B surface antigen. A worldwide epidemiologic and clinical survey. AB - Of 377 cases of fulminant hepatitis in persons positive for hepatitis B surface antigen (HBsAg) in Greece, Italy, the United States, the United Kingdom, the Central African Republic, Taiwan, Egypt, and India, only 52% could be attributed to infection with hepatitis B virus, which was defined as the presence of the IgM antibody to the hepatitis B core antigen (IgM anti-HBc) and the absence of serum markers of infection by extraneous viruses. Thirty percent of cases were caused by coinfection with hepatitis B virus and hepatitis delta virus or by infection with hepatitis delta virus superimposed on carriers of chronic HBsAg. In 18.5% of the patients, the absence of IgM anti-HBc indicated that they were not known to carry HBsAg, but no obvious superimposed factor of hepatitis could be identified. The cause of fulminant hepatitis is complex, and major risk factors are a pre existing HBsAg state and hepatitis delta virus infection. Superinfection of HBsAg carriers by non-A, non-B viruses seems to be the cause in a consistent proportion of cases. PMID- 3341676 TI - Certification in diagnostic laboratory immunology. PMID- 3341677 TI - Magnetic resonance imaging of the brain and spine. Health and Public Policy Committee, American College of Physicians. PMID- 3341678 TI - Establishing underground medical clinics in rural Afghanistan: the International Medical Corps experience. PMID- 3341679 TI - Bone densitometry. PMID- 3341680 TI - Familial dysalbuminemic hyperthyroxinemia in a Hispanic family. PMID- 3341681 TI - Remission of Graves disease and iodine intake. PMID- 3341682 TI - Marine omega-3 fatty acids and atherosclerosis. PMID- 3341683 TI - Ibuprofen and antihypertensive drugs. PMID- 3341684 TI - Verapamil and multifocal atrial tachycardia. PMID- 3341685 TI - Elastase activity in cigarette smokers. PMID- 3341686 TI - Transtracheal delivery of oxygen. PMID- 3341687 TI - Anaphylaxis and hydrocortisone. PMID- 3341688 TI - Aminophylline and chronic obstructive pulmonary disease. PMID- 3341689 TI - Heparin and deep venous thrombosis. PMID- 3341690 TI - Hematuria and Legionella pneumonia. PMID- 3341691 TI - Inhaled pentamidine and hypoglycemia. PMID- 3341692 TI - Disseminated-to-skin kala-azar and the acquired immunodeficiency syndrome. PMID- 3341693 TI - Cyclosporin in Wegener granulomatosis. PMID- 3341694 TI - Ranitidine and bradycardia. PMID- 3341695 TI - Flexible sigmoidoscopy for screening. PMID- 3341696 TI - "Medical clearance" and the "last hurdle". PMID- 3341697 TI - A jury of medical experts. PMID- 3341699 TI - Authorship and clinical trials. PMID- 3341698 TI - Influenza vaccine. PMID- 3341700 TI - Multiple otopathologic disorders. AB - Temporal bones (1,383) from 713 patients were studied systematically for multiple pathologic lesions. Eleven percent (152 temporal bones) were found to have more than one pathologic finding. Males (60.5%) had multiple diseases more commonly than did females (37.7%). The most frequently occurring findings were otitis media (71.1%), otosclerosis (43.4%), endolymphatic hydrops (38.8%), labyrinthitis (25.0%), and cancer (24.3%). We conclude that multiple coexisting pathologic conditions can have coincidental or causative relationships. The otolaryngologist should consider multiple pathologic conditions when diagnosing and treating diseases of the ear. PMID- 3341701 TI - Potentiation of ototoxicity by glutathione depletion. AB - The combination of 10 mg/kg ethacrynic acid (ETA) and 100 mg/kg kanamycin (KA) caused neither morphologic damage to the cochlea nor change in the auditory brain stem response of the chinchilla. However, after pretreatment with a single dose of buthionine sulfoximine (BSO; 800 mg/kg intraperitoneally) to reduce intracellular glutathione (gamma-glutamylcysteinylglycine; GSH) levels, the above single administration of ETA and KA resulted in complete deafness and severe morphologic damage. The kidney, which has a rapid GSH turnover and is therefore especially susceptible to GSH depletion by BSO, also demonstrated severe damage after this treatment. A similar rapid turnover of GSH and resulting limited capacity to detoxify reactive metabolites and free radicals may determine cochlear and renal vulnerability to this toxicity. These findings may explain the clinical observations of enhanced ototoxicity in patients administered amino glycoside antibiotics concomitantly with loop diuretics. PMID- 3341702 TI - Ultrastructural changes in vestibulo-ocular neurons following vestibular neurectomy in the cat. AB - Vestibulo-ocular (VO) neurons in the superior vestibular nucleus were labeled retrogradely with horseradish peroxidase and studied quantitatively using electron microscopy to determine the morphologic correlates of vestibular compensation. Eleven VO neurons from three normal cats were compared to 26 VO neurons in four animals killed 8 weeks after vestibular neurectomy and 13 VO cells from two animals killed 1 year after vestibular neurectomy. The results demonstrated a marked reduction (74%) in the number of synaptic profiles (SPs) on the VO cell soma in both experimental groups. Synaptic vesicles in the remaining SPs on VO neurons were fewer, smaller, and rounder than vesicles in control animals. The residual SPs also were associated with more asymmetric synapses. The experimental VO neuron showed a significant decrease in soma and organelles associated with protein synthesis. PMID- 3341703 TI - Morphologic effects of glycerol and urea on cochlear tissues of the chinchilla. AB - Glycerol and urea are used as test agents in confirming the diagnosis of endolymphatic hydrops. Although both substances act as osmotic diuretics, recent evidence suggests that they may have differing physiologic effects on the inner ear. This study was designed to compare the morphologic effects of urea and glycerol on cochlear tissues, using the chinchilla as an experimental model. Animals were given subcutaneous injections of glycerol (2 g/kg) or urea (1.2 g/kg) over periods of 3 hours, 4 days, or 1 week. Both agents were found to produce ultrastructural changes, including spiral ligament vacuolization, intracellular alterations of the stria vascularis, and increased numbers of Hensen's bodies in outer hair cells. These alterations appeared indicative of metabolic stress, but not toxicity. The morphologic findings provided no evidence that glycerol and urea affect the inner ear by fundamentally different mechanisms of action. PMID- 3341704 TI - Eliminating the Toynbee phenomenon in patients with nasal packs. AB - Nasal packing is a common procedure in otolaryngology, but is not a completely innocuous procedure. Besides aggravating mouth breathing, complete nasal obstruction results in an annoying Toynbee phenomenon. In patients with bilateral anterior nasal packing, we recorded high pressure gradients in the nasopharynx and, in consequence, in the middle ear. Patients in whom rubber tubes were inserted between the gauze layers of the anterior nasal packs suffered no such inconvenience and showed no such gradients. Our work proves the value of using these tubes for pressure equalization when nasal packs are necessary. PMID- 3341705 TI - Cochlear hair cell loss in ears with cholesteatomas. Scanning electron microscopy study. AB - Cochleas from 16 Mongolian gerbils with spontaneous aural cholesteatomas, and four of similar age without cholesteatomas, were examined by scanning electron microscopy to quantify cochlear hair cell loss. Loss of hair cell stereocilia was found in all ears with cholesteatomas and was significantly increased when compared with uninvolved ears from animals of similar age. The hair cell loss associated with gerbilline cholesteatomas appeared to be most marked in the middle turn of the cochlea and increased in severity with increasing size of the cholesteatomas. Outer hair cells were affected more than inner hair cells. Inner and outer hair cell loss was not significantly different in infected cholesteatomas versus sterile cholesteatomas. The greater damage to hair cells at the middle turn compared to the basal turn suggests that these losses may be the result of some agent acting through the cochlear wall rather than through the round window. PMID- 3341706 TI - Spinal accessory nerve function following neck dissection. AB - Spinal accessory nerve (SAN) function was evaluated by electromyography (EMG) and muscle testing in 36 patients who underwent neck dissection with SAN preservation. The results emphasized that SAN function was relatively good after conservative neck surgery. Muscle testing findings showed better function than did EMG findings. After surgery the trapezius muscle functioned more efficiently than the sternocleidomastoid (SCM) muscle probably because of the more traumatic surgical handling of both the SCM muscle and its SAN branch. In order to obtain the functional advantages of SAN preservation, the authors suggest that the conservative procedure in radical neck dissection be used whenever warranted by oncologic diagnosis. PMID- 3341707 TI - Stapedial electromyograms recorded by electrocochleography. AB - The stapedial reflex (SR) can be obtained by the impedance method only when the middle ear is intact. In order to examine the function of the stapedius muscle in diseased ears, the recording of the stapedial electromyogram by an electrocochleographic (ECoG) method was considered. The SR was recorded simultaneously by the impedance method in ten normal subjects for comparison. The outputs of ECoG were averaged by a signal processor up to 200 times under a longer sweep time, and a large biphasic wave with a latency of about 11 ms was obtained on the ECoG records. The amplitude increase of the biphasic wave caused by raising the intensity of the acoustic stimulation paralleled that of the SR. This means that the biphasic wave obtained by ECoG with a latency of about 11 ms originated from the stapedius muscle. PMID- 3341709 TI - Cerebrospinal fluid serous otitis media. PMID- 3341708 TI - Cochlea and heart as end-organs in small vessel disease. AB - Many studies have been done recently to determine the role of various stresses on the heart and peripheral vasculature. Although damage to coronary arteries and renal vessels has been well described, the ear as an end-organ in small vessel disease has been largely neglected. In a previous study, we examined the effects of noise, hypertension, and an atherogenic diet on the microvasculature of the cochleas in rats. The present study examines the effects of these stresses on the hearts of the same rats. The technique used to examine microvascular blood flow was the injection of unlabeled microspheres prior to killing. We found that the blood flow in the cochleas was reduced significantly in hypertensive animals exposed to noise or an atherogenic diet compared to that of normotensive or hypertensive control animals. The hearts of such animals, however, showed decreased myocardial blood flow only when compared to those of normotensive control animals, not when compared to those of hypertensive control animals. PMID- 3341710 TI - Pathology consultation. Sialadenosis. AB - Sialadenosis, characterized by a uniform hypertrophy and hyperplasia of the acinar parenchyma of salivary glands, is associated with a variety of systemic diseases or functional disorders. Present evidence relates the clinical and morphologic changes in the salivary tissues to a neuropathic alteration of the autonomic innervation of the salivary acini. PMID- 3341711 TI - Temporal bone collections in Europe and the United States. PMID- 3341712 TI - Surgical repair of the bilateral cleft of the primary palate. AB - A technique to repair clefts of the primary palate is described. This technique is a combination of several surgical methods previously reported to which some modifications have been added. The advantages of this technique are compared with those associated with other surgical methods. A more natural result is obtained with this technique: The undesirable vestibular fistula is avoided and a deeper buccal sulcus is achieved. The criteria in the management of the nose and orbicular muscle is analyzed. PMID- 3341714 TI - Studies on the endogenous flora of the human breast. AB - Identification of the endogenous microbiological flora of the human breast and its role in breast infections following subglandular augmentation or reduction mammaplasty was undertaken. A total of 231 cultures were performed on 59 breasts in 30 patients. Patients were followed for 12 months. No fungus was cultured from any specimen. Of the breasts cultured 53% were positive for coagulase-negative staphylococcus. Other aerobes found included diphtheroids, lactobacillus, D enterococcus, micrococcus, and alpha-hemolytic streptococcus. Propionibacterium acne was the most frequent anaerobic bacteria cultured. Other anaerobes included peptococcus and clostridium sporogenes. There was no correlation with respect to the type of bacterium and the depth within the breast where the culture specimens were taken. Postoperative wound infections developed in 2 of 19 patients undergoing reduction mammaplasty. Bacteria identical to those cultured at the time of surgery were again cultured from the wound. Twenty subglandular augmentation mammaplasties were performed with a 25% capsular rate at one year. Two capsules were associated with no bacterial growth at the time of mammaplasty surgery, whereas three were associated with coagulase-negative staphylococcus, Propionibacterium acne, and diphtheroids, respectively. Of the 15 breasts with no capsular contracture after one year, operative culture revealed coagulase negative staphylococcus in 8 and no bacterial growth in 7. Even breast tissue located deep within the gland away from the nipple contains a flora that is similar to that of normal skin. Cases of infection in which the endogenous bacteria were correlated with later infection was documented. PMID- 3341713 TI - Postoperative radiation and implant capsule contraction. AB - Occasionally radiation is required as adjunctive therapy following mastectomy for breast cancer. The effects of radiation on a developing implant capsule are unknown, but they are very important in relation to the increased use of immediate reconstruction. Experiments were performed on rabbits to study the effects of postoperative radiation therapy on capsule contraction and thickness. The results of these experiments suggest that radiation has no effect on implant capsules. PMID- 3341715 TI - Variations in flap blood flow and tissue PO2: a new technique for monitoring flap viability. AB - An implantable and disposable tissue oxygen tension (PO2) probe, useful as a clinical monitor following free-tissue transfer, is described. Experimentally, using the rabbit epigastric groin flap model, we have found it to be a sensitive indicator of arterial and venous occlusion. Oxygen can be given to verify the integrity of the monitoring technique and check any abnormal reading. Animals administered oxygen will have a rapid increase in tissue PO2 when the pedicle is intact. If compromised by arterial or venous occlusion, the low readings demonstrate no change. The application of this new technique for monitoring free flaps in 12 patients is presented. In 2 patients the tissue PO2 monitor successfully detected early vessel thrombosis, resulting in reexploration of the anastomoses and salvage of the free flaps. PMID- 3341716 TI - Topical 5-fluorouracil in treatment of carcinoma of nasal floor and nasal alae. AB - Squamous cell carcinomas of the nasal floor present problems for surgical therapy. Similarly, basal cell carcinoma of the nasal floor and alae requires extensive reconstruction when cures are obtained. To improve the results, we have treated the squamous cell carcinomas with topical 5-fluorouracil to obtain sensitization and shrinkage of the tumor before resection. The same has been done with basal cell carcinomas, but in selected patients the topical 5-fluorouracil has been continued until biopsies are negative. Thus, the costs of resection and reconstruction have been avoided and excellent cosmetic results are possible. This treatment is lengthy and requires weekly supervision. It offers a different approach that gives surgeons further options in treating these difficult carcinomas in carefully selected and cooperative patients. PMID- 3341717 TI - Rhinoplasty: nasal anatomy. AB - On the basis of over 100 fresh cadaver dissections as well as a review of nasal embryology and development, several important observations can be made regarding surgical anatomy of the nose. Within the bony vault, nasal profile modification consists of two distinct maneuvers: bony hump removal and modification of the nasofrontal groove area. The cartilaginous vault is in reality a unified, winged structure composed of septum and upper lateral cartilages. Within the nasal lobule, a continuous cartilaginous ring exists. The nose itself is covered by a superficial muscular aponenotic system. PMID- 3341718 TI - Vascularized innervated transfer of the clavicular head of the pectoralis major muscle in established facial paralysis. AB - Twenty cadaver dissections of the clavicular head of the pectoralis major muscle were carried out to determine the detailed anatomical arrangement of the vascular and nerve supply, with a view to using this muscle as an independent neuromyovascular unit in the treatment of established facial palsy. In all dissections, the muscle was found to have an independent nerve and vascular supply. A clinical case is reported with anatomical description and essential details of the operative technique. The ideal neuromyovascular unit is briefly described and the advantages of the pectoralis major for this use are illustrated. It is emphasized that limiting the goals of free muscle transfer to reanimation of the lower facial musculature will produce the most satisfactory results. PMID- 3341719 TI - Surgical management of severe mammary hidradenitis suppurativa. AB - Hidradenitis suppurativa is a devastating disease of the apocrine sweat glands. The chronic form is characterized by a malodorous discharge from multiple draining sinuses embedded in dense fibrous tissue, and physical discomfort. The disease commonly affects the axillary, perineal, and perianal regions. A case of hidradenitis suppurativa of the mammary gland necessitating mastectomy is presented here to illustrate the severity of the disease at an uncommon site. As in other regions of the body, aggressive surgical intervention provides a chance for rapid recovery. The surgical treatment should be tailored to the severity of the disease. PMID- 3341720 TI - Craniocarpotarsal dysplasia: the whistling face syndrome. AB - Currently, 50 cases of craniocarpotarsal dysplasia, or whistling face syndrome (WFS), have been reported, with more than 60 anatomical anomalies involving the head, hands, and feet, in addition to the face. In spite of the fact that there is much information concerning the surgical correction of many of these deformities, such as the surgical program for the hands outlined by Call and Strickland in 1981, there is little information concerning the surgical correction of facial deformities. In view of this, we present here a case report of a patient with WFS and our surgical approach to the facial deformities involved. Since January 24, 1983, when this 7-year-old girl first came into our care, she has successfully undergone a total forehead reshaping, correction of congenital upper eyelid ptosis, and a bilateral commissuroplasty. Follow-up for more than three years has shown stable surgical results. PMID- 3341721 TI - Further application of supratrochlear vessels to facial repair. AB - We performed transplantations of cranial bone and scalp using the supratrochlear vessels as a pedicle. We confirmed that these vessels could be used for moving the tissues between the eyebrow and the coronal suture. PMID- 3341722 TI - The incredible T vein graft: developing increased microsurgical skill through a competitive student exercise. AB - We developed an exercise to encourage microsurgery students to practice technically difficult procedures. The incredible T exercise uses the contralateral femoral vein of the rat as an interpositional graft into the femoral vein and the inferior epigastric vein as an end-to-side anastomosis into the graft. The technically difficult procedure requires students to practice and improve their surgical technique, thereby gaining skill and self-confidence. Friendly competition helps to make the learning process more enjoyable. PMID- 3341723 TI - Re: Brennan: Ptotic chin syndrome. PMID- 3341724 TI - Preoperative anxiety. Its affect on cognitive thinking. PMID- 3341725 TI - Delegation: the art of letting go. PMID- 3341726 TI - Preparing children for surgery. Learning through play. AB - The approach that Children's Hospital has taken in preparing children for surgery, both ambulatory and extended recovery, is exciting and challenging. The staff is encouraged by the positive response of the patients and families who participate in the tour and the doll demonstrations. PMID- 3341727 TI - Parental presence during anesthesia induction. A research study. PMID- 3341728 TI - Defining the characteristics of a positive, enthusiastic staff. PMID- 3341729 TI - Extracorporeal shock wave lithotripsy. A procedural review. PMID- 3341731 TI - RN first assistant 1987 survey update. PMID- 3341730 TI - Thermo-resuscitation for postoperative hypothermia. Using reflective blankets. PMID- 3341732 TI - Coordinator teaches staff to operate equipment, handles malfunctioning equipment. AB - Based on the data collection, a recommendation was made to the OR committee to develop a new full-time position of equipment coordinator. Committee members supported the recommendation, and further recommended that a backup person be trained as an assistant equipment coordinator to cover when the equipment coordinator was not available. PMID- 3341733 TI - Interchanging different product components; instilling eye drops before patient signs consent. PMID- 3341734 TI - Pat Hercules: setting goals helps her succeed. Interview by Susan Schlepp. PMID- 3341735 TI - Isolation and primary structure of the major toxin from sea snake, Acalyptophis peronii, venom. AB - The major neurotoxin from the venom of Acalyptophis peronii captured in the Gulf of Thailand was isolated. Although there are two toxic fractions in the venom, the most toxic and abundant fraction was selected for purification and chemical characterization. The LD50 of the major toxin is 0.125 micrograms/g mice, indicating an extremely toxic nature. The toxin consists of 60 amino acid residues with methionine as the amino-terminal and asparagine as the carboxy terminal end. It contains nine half-cystine residues. There is 1 mol each of tryptophan, tyrosine, methionine, valine, aspartic acid, leucine, and alanine, and there is no phenylalanine. The molecular weight calculated from the amino acid sequence determination was 6600. The toxin replaces alpha-bungarotoxin in binding with the acetylcholine receptor, indicating that the A. peronii major neurotoxin competes with alpha-bungarotoxin for the same binding site of the acetylcholine receptor. PMID- 3341736 TI - Light inhibition of mitochondrial respiration in a mutant of Chlamydomonas reinhardtii devoid of ribulose-1,5-bisphosphate carboxylase/oxygenase activity. AB - The effect of light on mitochondrial respiration has been investigated in Chlamydomonas reinhardtii rcl-u-1-10-6C, a mutant devoid of ribulose-1,5 bisphosphate carboxylase/oxygenase (Rubisco) activity. No CO2 uptake was observed in the light, confirming that there was no Rubisco activity, but the CO2 evolution rate was diminished by 65 to 80%. This inhibition was ascribable to a decrease in the tricarboxylic acid cycle (Krebs cycle) activity. At the same time, O2 evolution associated with stimulation of the O2 uptake appears. Darkness or addition of DCMU fully reversed the effect of light, indicating that the inhibitory process is linked to photosystem activities. Levels of pyridine nucleotides (NAD(H) and NADP(H)) and adenine nucleotides (ATP and ADP), the most probable mediators of the interaction between photosynthesis and respiration, were measured in dark and in light. During a dark to light transition the level of NADPH increased significantly whereas the NAD(H) pool remained almost fully oxidized. The level of ADP was always extremely low. These results suggest that the inhibition of Krebs cycle activity is due to a competition for cytosolic ADP between chloroplastic photophosphorylations and oxidative phosphorylations. PMID- 3341737 TI - The biosynthesis of sulfoquinovosyldiacylglycerol: studies with groundnut (Arachis hypogaea) leaves. AB - The biosynthetic pathway of sulfoquinovosyldiacylglycerol (SQDG) was investigated using groundnut (Arachis hypogaea) leaf discs and 35S-labeled precursors. [35S]SO4(2-) was actively taken up by the leaf discs and rapidly incorporated into SQDG. After 2 h, 1.5% of the [35S]SO4(2-) added to the incubation medium was taken up, of which 28% was incorporated into SQDG. The methanol-water phases of the lipid extracts of the leaf discs were analyzed for the 35S-labeled intermediates. Up to 2 h of incubation, cysteic acid, 3-sulfopyruvate, 3 sulfolactate, 3-sulfolactaldehyde, and sulfoquinovose (SQ) which have been proposed as intermediates [Davies et al. (1966) Biochem. J. 98, 369-373] were not labeled. Only a negligible amount of radioactivity was observed in these compounds after incubation for 4 h and more. Addition of sodium molybdate inhibited the uptake of [35S]SO4(2-) as well as its incorporation into SQDG by the leaf discs, suggesting that 3'-phosphoadenosine-5'-phosphosulfate may be involved in the biosynthesis of SQDG. Addition of unlabeled cysteic acid to the incubation medium enhanced the uptake of [35S]SO4(2-) but did not affect its incorporation into SQDG. 35S-labeled cysteic acid was taken up by the leaf discs and metabolized to sulfoacetic acid but not incorporated into SQ or SQDG. These results show that cysteic acid is not an intermediate in SQDG biosynthesis. [35S]SQ was taken up by the leaf discs and incorporated into SQDG in a time dependent manner. [35S]Sulfoquinovosylglycerol was also taken up by the leaf discs but not incorporated into SQDG. It is concluded that SQDG is not biosynthesized by the proposed sulfoglycolytic pathway in higher plants. Though [35S]SQ was converted to SQDG, the rates are much lower compared to [35S]SO4(2-) incorporation, which suggests that a more direct pathway involving sulfonation of a lipid precursor may exist in higher plants. PMID- 3341738 TI - The effects of alpha-tocopherol on site-specific lipid peroxidation induced by iron in charged micelles. AB - alpha-Tocopherol inhibited H2O2-Fe2+-induced lipid peroxidation of linoleic acid (LA) by scavenging OH radicals in tetradecyltrimethylammonium bromide (TTAB) micelles. The inhibiting ability of alpha-tocopherol was much greater than that of OH-radical scavengers mannitol and t-butanol. In contrast, alpha-tocopherol enhanced linoleic acid hydroperoxide (LOOH)-Fe2+-induced lipid peroxidation through regeneration of Fe2+ in sodium dodecyl sulfate (SDS) micelles containing LA. alpha-Tocopherol was oxidized by Fenton's reagent (FeSO4 + H2O2) at a higher rate in SDS micelles than in TTAB micelles. The likely oxidants were OH radicals in the former and Fe3+ in the latter. Both reagents formed in the Fenton reaction. Ferrous ion catalyzed in a dose-dependent manner the decomposition of LOOH and conjugated diene compounds in SDS but not in TTAB micelles. alpha Tocopherol and Fe3+ individually had no effect on the decomposition of LOOH, but together were quite effective. The rate of the decomposition was a function of the concentration of alpha-tocopherol. The mechanism of "site-specific" antioxidant action of alpha-tocopherol in charged micelles is discussed. PMID- 3341739 TI - The glycosphingolipid composition of the placenta of a blood group P fetus delivered by a blood group Pk1 woman and analysis of the anti-globoside antibodies found in maternal serum. AB - To further define the molecules that may mediate spontaneous abortion due to maternal-fetal blood group incompatibility within the P blood group system, we have examined the fine specificities of maternal antibodies and the glycolipid antigens from the placenta of a P infant born to a Pk1 mother. Maternal antibodies obtained during therapeutic plasmapheresis were analyzed to determine their reactivities with placental glycolipid extracts on thin-layer plates. Second antibodies specific for IgM, IgG, and IgA revealed immunoglobulins of all of these classes strongly reactive with one major placental glycolipid that comigrates with globoside. GC/MS analysis confirmed that the major P-active pentaglycosylceramide of placenta has the same structure as that previously shown for the P antigen of red blood cells: GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc Cer. Serum antibodies partially purified by affinity chromatography on globoside octyl-Sepharose specifically recognize glycolipids that contain terminal GalNAc beta 1-3Gal . . . residues and also recognize the same sequence as an internal determinant in some, but not all, glycolipids with extended globoside core regions. Thus, in the blood group P incompatible fetus, the major P antigen present in placenta has the same carbohydrate structure as the P antigen present in fetal and adult erythrocytes and might be a target for the maternal immune system. PMID- 3341740 TI - Photosynthesis in phosphoenolpyruvate carboxykinase-type C4 plants: pathways of C4 acid decarboxylation in bundle sheath cells of Urochloa panicoides. AB - The mechanism of C4 acid decarboxylation was studied in bundle sheath cell strands from Urochloa panicoides, a phosphoenolpyruvate carboxykinase (PCK)-type C4 plant. Added malate was decarboxylated to give pyruvate and this activity was often increased by adding ADP. Added oxaloacetate or aspartate plus 2 oxoglutarate (which produce oxaloacetate via aspartate aminotransferase) gave little metabolic decarboxylation alone but with added ATP there was a rapid production of PEP. For this activity ADP could replace ATP but only when added in combination with malate. In addition, the inclusion of aspartate plus 2 oxoglutarate with malate plus ADP often increased the rate of pyruvate production from malate by more than twofold. Experiments with respiratory chain inhibitors showed that the malate-dependent stimulation of oxaloacetate decarboxylation (PEP production) was probably due to ATP generated during the oxidation of malate in mitochondria. We could provide no evidence that photophosphorylation could serve as an alternative source of ATP for the PEP carboxykinase reaction. We concluded that both PEP carboxykinase and mitochondrial NAD-malic enzyme contribute to C4 acid decarboxylation in these cells, with the required ATP being derived from oxidation-linked phosphorylation in mitochondria. PMID- 3341741 TI - Binding of immunoglobulins to the major progesterone-induced proteins secreted by the sheep uterus. AB - We examined the binding of immunoglobulins to the uterine milk proteins, the major progesterone-induced proteins secreted by uterine endometrium of pregnant ewes. Binding was ascertained by measuring binding of 125 I-immunoglobulin to uterine milk proteins that were Western or dot-blotted to nitrocellulose or were coupled to Sepharose. The magnitude of binding was greatest for sheep IgM, intermediate for sheep secretory IgA, low for human secretory and serum IgA, and barely detectable for sheep IgG. Binding of IgA and IgM to uterine milk proteins was time and concentration dependent, saturable, inhibited by high ionic strength buffers, and lost due to enzymatic destruction of the Fc portion of the immunoglobulin molecule. In conclusion, the uterine milk proteins preferentially bind IgA and IgM in a species-dependent manner. Such binding may be related to the role of these proteins in the uterus and may make the uterine milk proteins a useful tool for studying or purifying sheep immunoglobulins. PMID- 3341742 TI - Enhancement of macromolecular ligand binding by rabbit alveolar macrophages by mannose oligosaccharides and related compounds. AB - When rabbit alveolar macrophages were incubated with 10 mM D-mannose, binding of macromolecular ligands containing D-mannose, such as bovine serum albumin modified with mannose (Man-BSA), was enhanced more than 100%, but was inhibited at higher concentrations [C.A. Hoppe and Y. C. Lee (1982) J. Biol. Chem. 257, 12831-12834]. This phenomenon was further investigated with ovalbumin-derived glycopeptide, Asn(GlcNA2,Man5), and with a wide variety of synthetic mannose oligosaccharides. The extent of enhancement is related to the fine structure of the oligosaccharide groups, but the results are complicated by concurrent inhibition exerted by these compounds. It appears that the more inhibitory a compound is, the less capable it is of exerting the enhancement effect. Thus, small mannose derivatives such as glycosides, including clustered mannosides based on tris(hydroxymethyl)aminomethane [Y. C. Lee (1978) Carbohydr. Res. 67, 509-514], and most of the biantennary mannose oligosaccharides were found to be effective in enhancing the binding of radiolabeled Man-BSA. Triantennary oligosaccharides, on the other hand, showed only a slight enhancement effect and a much stronger inhibitory effect. The effects of ligand size, valency, as well as the fine structure on enhancement are discussed. PMID- 3341743 TI - Monoterpene cyclases: physicochemical features required for pyrophosphate binding determined from inhibition by structural analogs. AB - Monoterpene cyclases catalyze the divalent metal ion-dependent conversion of geranyl pyrophosphate, the ubiquitous C10 intermediate of isoprenoid biosynthesis, to a variety of monoterpene skeletons, and the pyrophosphoryl moiety is a primary determinant for substrate binding by these enzymes. To determine what specific features of this functional group are critical for enzymatic recognition, inorganic pyrophosphate and a series of structurally related analogs were examined as inhibitors of geranyl pyrophosphate:(+)-alpha pinene cyclase and geranyl pyrophosphate:(+)-bornyl pyrophosphate cyclase from sage (Salvia officinalis). Analysis of trends in the magnitude of inhibition by the analogs relative to inorganic pyrophosphate indicated that the combination of ionization state (formal charge) at the enzymatic pH optimum, ability to chelate divalent metal ions, and intramolecular flexibility is required for effective interaction with both cyclases. Only when all of these criteria are met is inhibition of cyclization comparable to that observed with inorganic pyrophosphate. PMID- 3341744 TI - The action of the sesquiterpenic benzoquinone, perezone, on electron transport in biological membranes. AB - Perezone (2-(1,5-dimethyl-4-hexenyl)-3-hydroxymethyl-p-benzoquinone) is a sesquiterpenic benzoquinone isolated from roots of plants of the genus Perezia. It exhibits oxido-reduction characteristics which suggest that the compound can be used for studies of the electron transfer chain of rat liver mitochondria. Perezone at 50 microM inhibits mitochondrial electron transport through a process which differs from that of rotenone, amytal, and Antimycin A. The inhibition is temperature dependent; at 35 degrees C it fails to inhibit valinomycin-induced mitochondrial respiration, but at 20 degrees C it inhibits respiration by 80-90%. Perezone is an electron-donor and electron-acceptor compound that behaves similarly to naphtoquinone. It mediates electron transport from a reaction center preparation isolated from Rhodopseudomonas sphaeroides and added cytochrome c. The low respiration of rat liver mitochondria depleted of coenzyme Q10 (CoQ) is increased by perezone. The electron transport activity of perezone was also demonstrated with CoQ-deficient yeast mutant E3-24. PMID- 3341745 TI - Non-protein-mediated transfer of phosphatidic acid between microsomal and mitochondrial membranes. AB - The transfer of phosphatidic acid between rat liver microsomes loaded with [32P] phosphatidic acid and rat liver mitochondria was studied in the absence of added lipid transfer proteins. It was found that during 1 h at 37 degrees C in the medium containing 100 mM KCl, 20-30% of phosphatidic acid but only 2.5% of phosphatidylcholine were transferred. This spontaneous transfer of phosphatidic acid remained the same after pretreatment of microsomes and mitochondria with 125 mM KCl or microsomes alone with 1 mM Tris, pH 8.6, procedures reported to remove adsorbed lipid transfer proteins. This transfer was insensitive to thiol-blocking reagents. The initial rate of this non-protein-mediated transfer of phosphatidic acid was virtually independent of the concentration of the acceptor membranes (mitochondria), thus indicating that it occurs by diffusion of the phospholipid through the aqueous phase rather than by membrane collision. About 80% of phosphatidic acid synthesized in the outer mitochondrial membrane was recovered in the inner membrane after a 1-h incubation, pointing to a high rate of the intermembrane transfer of this phospholipid within intact mitochondrion. PMID- 3341746 TI - Effects of glucose starvation and puromycin treatment on lipid-linked oligosaccharide precursors and biosynthetic enzymes in Chinese hamster ovary cells in vivo and in vitro. AB - Previous studies from several laboratories have demonstrated that glucose-starved Chinese hamster ovary (CHO) cells and other cells in culture switch from synthesis of the normal Glc3Man9GlcNAc2-P-P-Dol to Man5-GlcNAc2-P-P-Dol. In this study we have investigated this phenomenon in CHO cells in vitro and in vivo in order to determine the possible site of this block. Our results demonstrate that enzymatic activities responsible for Man9GlcNA2 synthesis in vitro are normal in glucose-starved cells. In vivo, however, the pool of GDP-[3H]Man is severely depleted, while [3H]mannose incorporation into lipid-linked and protein-bound Man5GlcNAc2 is increased. This result suggests that the available GDP-Man in starved cells is utilized to synthesize Man5GlcNAc2 preferentially, resulting in a reduction of Dol-P-Man and Man6-Man9 GlcNAc2 synthesis in vivo in glucose starved cells. Conditions which prevent the depletion of GDP-[3H]Man in glucose starved cells, such as puromycin or cycloheximide treatment, result in normal synthesis of Man9GlcNAc2 by glucose-starved cells. An unexpected finding in the course of this study is that puromycin or cycloheximide treatment of cells, which is known to inhibit lipid-linked oligosaccharide synthesis in glucose-fed cells, has no such inhibitory effect on glucose-starved cells. PMID- 3341747 TI - Characteristics of thymidylate synthase purified from a human colon adenocarcinoma. AB - Thymidylate synthase has been purified greater than 4000-fold from a human colon adenocarcinoma maintained as a xenograft in immune-deprived mice. In this disease, the enzyme is an important target for the cytotoxic action of 5 fluorouracil, which is influenced by the reduced folate substrate CH2-H4PteGlu. Due to the importance of this interaction, and the existence in cells of folate species as polyglutamyl forms, the interaction of folylpolyglutamates with thymidylate synthase was examined. Polyglutamates of PteGlu were used as inhibitors, and the interaction of CH2-H4PteGlu polyglutamates as substrates or in an inhibitory ternary complex were also examined. Using PteGlu1-7, Ki values were determined. A maximal 125-fold decrease in Ki was observed between PteGlu1 and PteGlu4; further addition of up to three glutamyl residues did not result in an additional decrease in Ki. Despite the increased binding affinity of folypolyglutamates for this enzyme, no change in the Km values for either dUMP (3.6 microM) or CH2-H4PteGlu (4.3 microM) were detected when polyglutamates of [6R]CH2-H4PteGlu were used as substrates. Product inhibition studies demonstrated competitive inhibition between dTMP and dUMP in the presence of CH2-H4PteGlu5. In addition, CH2-H4PteGlu4 stabilized an inhibitory ternary complex formed between FdUMP, thymidylate synthase, and CH2-H4PteGlu4. Thus the data do not support a change in the order of substrate binding and product release upon polyglutamylation of CH2-H4PteGlu reported for non-human mammalian enzyme. This is the first study to characterize kinetically thymidylate synthase from a human colon adenocarcinoma. PMID- 3341748 TI - Molecular and catalytic properties of a butyrylesterase from human red cells and brain. AB - A butyrylesterase from human red cells was prepared to homogeneity using DEAE cellulose, Ultrogel ACA-34, DEAE-Sephacel, and precipitation with 1.5 M (NH4)2SO4. The yield was 25-35% relative to the enzyme activity of the hemolysate. Because of its preference for butyric acid esters the enzyme was designated a butyrylesterase. With alpha-naphthyl butyrate the Km was 7.6 microM and the kcat, 48 s-1. The molecular weight was 340,000 and the subunit weight 85,000, indicating a tetrameric structure. The isoelectric pH was 4.0. The enzyme preparation did not contain cystine. Sialic acid or other carbohydrate components could not be detected. The enzyme was irreversibly inhibited by organophosphate esters and the second-order rate constant was 192 M-1 s-1 for diethyl p nitrophenyl phosphate. For the brain enzyme the constant was 206 M-1 s-1. The enzyme was irreversibly inhibited by sulfhydryl reagents, indicating that the enzyme is a sulfhydryl-dependent serine esterase. The enzyme was identical to the butyrylesterase from human brain, and the two enzymes were immunochemically identical. An amino acid ester has been shown to be split at a higher rate than butyric acid esters; however, the specificity constant (kcat/Km) was lower for the amino acid ester than for the butyric acid ester. The enzyme did not exhibit amidase activity. PMID- 3341749 TI - Effects of hypophysectomy and administration of growth and thyroid hormones on the hydroperoxide-induced calcium release process and glutathione levels in rat liver mitochondria. AB - In order to investigate the effects of growth and thyroid hormones on Ca2+ transport in liver mitochondria, Ca2+ release and other accompanying changes induced by t-butylhydroperoxide were measured in mitochondria from hypophysectomized and hormone-injected rats. Mitochondria from normal and hypophysectomized rats showed similar rates of Ca2+ uptake (40 nmol.min.-1 mg protein-1) and ruthenium red-insensitive release (3 nmol.min.-1 mg protein-1). However, the t-butylhydroperoxide (0.5 mM)-induced release of 90% of the added Ca2+ required 1027 +/- 98 and 560 +/- 35 s in the hypophysectomized and normal groups, respectively, and the difference was independent of Ca2+. The release was accompanied by a loss of membrane potential, large amplitude swelling, the oxidation of NAD(P)H and stimulation of respiration. At conditions of equivalent release rates, the rate and extent of swelling as well as the stimulation of respiration were lower in mitochondria from hypophysectomized rats than those in the normal group. These results were confirmed by electron microscopy and provided evidence for a dissociation between the release of Ca2+ and the increase of membrane permeability. The administration of bovine growth hormone and/or 3,5,3'-triiodo-L-thyronine to hypophysectomized rats decreased the Ca2+ release times by different degrees and thyroid hormone was more effective than growth hormone. Hypophysectomy doubled the GSH content and hormone injections decreased it and the Ca2+ release times in parallel. Indeed, a high degree of correlation (r = 0.96) was obtained between mitochondrial GSH and the release times from groups of differing hormone status. Differences in the groups in the time required for oxidation of 80-90% of GSH were correlated with the differences in the times for release of 90% Ca2+. Therefore, these results demonstrated that growth and thyroid hormones can alter both the hydroperoxide-induced Ca2+ release and the metabolism of GSH in liver mitochondria, suggesting that the two processes are related. It is proposed that the effects of these hormones on Ca2+ transport may result from the promotion of its efflux from mitochondria and its mobilization into the cytosol. PMID- 3341751 TI - Purification, properties, and evidence for two subtypes of human placenta hexokinase type I. AB - In human placenta 85% of total hexokinase activity (EC 2.7.1.1) was found in a soluble form. Of this, 70% is hexokinase type I while the remaining 30% is hexokinase type II. All the bound hexokinase is type I. Soluble hexokinase I was purified 11,000-fold by a combination of ion-exchange chromatography, affinity chromatography, and dye-ligand chromatography. The specific activity was 190 units/mg protein with a 75% yield. The enzyme shows only one band in nondenaturing polyacrylamide gel electrophoresis that stains for protein and enzymatic activity; however, two components (with Mr 112,000 and 103,000) were constantly seen in sodium dodecyl sulfate-gel electrophoresis. Many attempts were made to separate these two proteins under native conditions; however, only one peak of activity was obtained when the enzyme was submitted to gel filtration (Mr 118,000), preparative isoelectric focusing (pI 5.9), anion-exchange chromatography, hydroxylapatite chromatography, and affinity chromatography on immobilized dyes and immobilized glucosamine. The high and low molecular weight hexokinases show the same isoelectric point under denaturing conditions as determined by two-dimensional gel electrophoresis. Each hexokinase subtype was obtained by preparative sodium dodecyl sulfate electrophoresis followed by electroelution. Monospecific antibodies raised in rabbits against electroeluted high and low molecular weight hexokinases were not able to recognize the native enzymes but each of them detected both hexokinases on immunoblots. Amino acid compositions and peptide mapping by limited proteolysis of the high and low molecular weight hexokinases were also performed and suggested a strong homology between these two subtypes of human hexokinase I. PMID- 3341752 TI - Identification of the multifunctional calmodulin-dependent protein kinase in the cytosol, sarcoplasmic reticulum, and sarcolemma of rabbit skeletal muscle. AB - A multifunctional calmodulin-dependent protein kinase (calmodulin kinase) was purified from the cytosol of rabbit skeletal muscle as a subunit of 58 kDa. A 58 kDa protein in sarcoplasmic reticulum (SR) and sarcolemma (SL) of rabbit skeletal muscle was endogenously phosphorylated in a calmodulin-dependent manner. The 58 kDa protein in SR and SL was considered to be identical to the subunit of cytosol calmodulin kinase on the basis of immunoreactivity, calmodulin binding, and autophosphorylation studies and on the patterns of protease-treated phosphopeptides. Calmodulin kinase showed broad substrate specificity and phosphorylated troponins I and T. PMID- 3341753 TI - Occurrence of platelet-activating factor in rabbit spermatozoa. AB - Spermatozoa obtained from rabbit ejaculate were analyzed for the presence of platelet-activating factor [PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC)] by using standard HPLC and TLC procedures. Fractions corresponding to synthetic PAF (AGEPC) revealed PAF-like activity amounting to 0.35 +/- 0.06 pmol/10(8) cells (mean +/- SE) as determined by bioassays based on the release of [3H]serotonin from washed rabbit platelets. This activity was lost upon base catalyzed methanolysis, but was restored to the original level after reacetylation. Analysis of the phosphatidylcholine (PC) fraction by GC-MS subsequent to base-catalyzed methanolysis showed that 1-O-alkyl-2 acylphosphocholine comprises about 12% of the PC fraction with alkyl chain lengths of 16:0 (88%) and 18:0 (12%). PMID- 3341750 TI - Hydroxyamino acid specificity of smooth muscle myosin light chain kinase. AB - Synthetic peptides corresponding to the phosphorylation site in the myosin regulatory light chain from smooth muscle, Lys-Lys-Arg-Ala-Arg-Ala-Thr-Ser-Asn Val-Phe-Ala ([Ala14,15]MLC(11-23] and containing a variety of hydroxyamino acid analogs at position 19, were tested as substrates for the smooth muscle myosin light chain kinase. Peptide analogs containing either D-serine or cis hydroxyproline were not phosphorylated. The corresponding trans-hydroxyproline containing peptide was poorly phosphorylated with a Km of 2.3 microM and a Vmax of 3 X 10(-3) mumol.min-1.mg-1 compared to a Km of 12.5 microM and a Vmax of 1.43 mumol.min-1.mg-1 for the parent peptide. All three hydroxyamino acid analog peptides acted as relatively potent inhibitors of myosin light chain phosphorylation with Ki values in the range 7.5-10 microM, comparable to 7 microM for the parent peptide. Thus the failure of the hydroxyamino acid analog peptides to act as effective substrates was not the result of poor binding to the enzyme. In contrast, the same substitutions made in the peptide substrate for the cAMP dependent protein kinase resulted in poor inhibitors. It is likely that the hydroxyl group of the substituting amino acids in the myosin light chain peptide analogs is not presented in the correct orientation in the active site for transfer of the phosphate group. PMID- 3341754 TI - Glycoconjugates secreted by bovine tracheal serous cells in culture. AB - Glycoconjugates secreted by bovine tracheal gland serous cells in culture were characterized after incorporation of radioactive precursor [1-14C]glucosamine and stimulation with isoproterenol. Under dissociative conditions, glycoconjugates eluted in both the void and included volumes on Sepharose Cl-4B. Fractionated by anion-exchange chromatography, the high-molecular-weight (Sepharose Cl-4B; V0) glycoconjugates gave two acidic fractions eluting at 0.5 and 2.0 M NaCl; low molecular-weight glycoconjugates of the included volumes gave a neutral fraction and two acidic fractions eluting at 0.5 and 2.0 M NaCl. Based on chemical analysis and specific enzymatic digestions, the material eluting in the void volume was shown to contain hyaluronic acid and chondroitin sulfate proteoglycan. In addition, the presence of small amounts of galactose, fucose, sialic acid, glucosamine, and galactosamine suggest the presence of O-glycosidically linked glycoproteins in the void volume. The identification of galactosaminitol in beta eliminated oligosaccharides from this material confirms this notion. The material eluting in the included volume was shown to contain N-linked glycoproteins with glycans of complex type in the neutral fraction and chondroitin sulfate proteoglycans in the two acidic fractions. Significant N-sulfation of amino sugars was detected in the 0.5 M acidic fraction, indicating the presence of heparan sulfate. Hyaluronic acid and chondroitin sulfate proteoglycan have recently been identified in tracheal secretions; our results suggest that these components originate at least in part from tracheal gland serous cells. PMID- 3341756 TI - Differential inactivation of plant lauric acid omega- and in-chain-hydroxylases by terminally unsaturated fatty acids. AB - The microsomal fraction from Vicia sativa L. cv. Septimane contains a cytochrome P-450-dependent lauric acid omega-hydroxylase that is inactivated in a time dependent, pseudo-first-order manner when the microsomes are incubated with 11 dodecynoic acid. The rate constant for the inactivation is approximately 4.3-4.8 X 10(-3) s-1. In contrast, the olefinic analog 11-dodecenoic acid is primarily a time-independent inhibitor of the omega-hydroxylase. 1-Aminobenzotriazole, 3 phenoxy-1-propyne, and 3-(2,4-dichlorophenoxy)-1-propyne, mechanism-based inactivators of cinnamic acid 4-hydroxylase, and 9-decenoic acid, a mechanism based inactivator of the lauric acid in-chain hydroxylase, are at best poor inactivators of the omega-hydroxylase. Conversely, cinnamic acid 4-hydroxylase is only slightly affected by concentrations of 11-dodecynoic acid that completely inactivate the omega-hydroxylase. 11-Dodecynoic acid is thus a potent, relatively specific, inactivator of the V. sativa lauric acid omega-hydroxylase. PMID- 3341755 TI - The essential role of cobalt in the inhibition of the cytosolic isozyme of 3 deoxy-D-arabino-heptulosonate-7-phosphate synthase from Nicotiana silvestris by glyphosate. AB - The prime molecular target of glyphosate (N-[phosphonomethyl]glycine), a potent herbicidal and antimicrobial agent, is known to be the shikimate-pathway enzyme, 5-enol-pyruvylshikimate-3-phosphate synthase. Inhibition by glyphosate of an earlier pathway enzyme that is located in the cytosol of higher plants, 3-deoxy-D arabino-heptulosonate-7-phosphate synthase (DS-Co), has raised the possibility of dual enzyme targets in vivo. With the recent appreciation that magnesium (and manganese) can replace cobalt as the divalent-metal activator of DS-Co, it has now been possible to show that sensitivity of DS-Co to inhibition by glyphosate is obligately dependent upon the presence of cobalt. Evidence for a cobalt(II):glyphosate complex with octahedral coordination was obtained through examination of the effect of glyphosate upon the visible electronic spectrum of aqueous solutions of cobalt(II) chloride. The presence of glyphosate increased the concentration of cobalt(II) chloride required for enzyme activity, and the concentration of cobalt(II) chloride markedly affected the concentration of glyphosate required for inhibition of DS-Co activity. The extent to which DS-Co is vulnerable to inhibition by glyphosate in vivo depends, therefore, upon the unknown extent to which DS-Co molecules in the cytosol might be associated with cobalt. PMID- 3341757 TI - Characterization of DNA polymerase alpha activity from a mouse DNA temperature sensitive mutant, strain tsFT20, which shows a defect in DNA polymerase alpha activity at restrictive temperatures. AB - tsFT20 cells derived from mouse FM3A cells are DNA temperature-sensitive mutants, which have heat-labile DNA polymerase alpha activity. When tsFT20 cells were incubated at restrictive temperatures, intracellular levels of DNA polymerase alpha activity changed biphasically, showing an initial fast decrease (phase I) and a subsequent slow decrease (phase II). The activity of DNA polymerase alpha from tsFT20 cells cultured at a permissive temperature (33 degrees C) was greatly increased by the addition of glycerol or ethylene glycol to the reaction mixture, while little increase in enzyme activity was observed at any concentration of glycerol or ethylene glycol tested with the enzyme from the cells cultured at a restrictive temperature (39 degrees C) for 8 h (phase II). The activity of DNA polymerase alpha from wild-type cells was also increased by the addition of glycerol but the increase was much less than that in the tsFT20 cells. An in vitro preincubation experiment showed that DNA polymerase alpha from tsFT20 cells cultured at 33 degrees C very rapidly lost its ability to be stimulated by glycerol. Furthermore, the experiment using the extracts prepared from tsFT20 cells cultured at 39 degrees C for various periods showed that the ability to be stimulated by glycerol decreased with the duration of incubation time at 39 degrees C. DNA polymerase alpha from the revertants, which can grow at 39 degrees C and exhibit a partial recovery in heat stability of DNA polymerase alpha activity, showed an intermediate response to glycerol, between those of DNA polymerase alpha from tsFT20 and from the wild-type cells. Finally, it was observed that the level of enzyme activity that can be stimulated by glycerol correlated well with the DNA synthesizing ability of tsFT20 cells. PMID- 3341758 TI - Interrelation between the charge isoforms of mammalian ornithine decarboxylase. AB - Ornithine decarboxylase (ODC) isolated from a variety of tissues has been separated, using DEAE ion-exchange chromatography, into multiple peaks of activity that appear to be related to control of this enzyme stability. Reports of these charge isoforms in current literature are generally unclear as to whether these represent a covalent posttranslational modification or merely an alteration in structural conformation or association. In this study we investigated the relationship of this form separation to the degree of enzyme polymerization, interaction with other proteins and buffer components, and the multiple isoelectric forms of this enzyme noted in denaturing concentrations of urea. High-performance chromatography techniques were used to demonstrate that two of the major enzyme forms, ODC I and II, are really monomers of the enzyme, while minor peaks of activity frequently observed to elute after ODC II contain various dimeric enzyme states. Pyridoxal 5'-phosphate (0.05 mM) added to isolated enzyme preparations composed of I and II monomers induced the formation of I and II dimers as well as a mixed I-II dimer. All three dimer forms were observed to be natural components of freshly isolated crude cell homogenates. The charge distinction between the monomer forms I and II was found to be maintained during ion-exchange chromatography in the presence of 8 M urea, and the enzyme isoforms demonstrated distinct bands on isoelectric focusing gels run in the presence of 9 M urea. Thus, although some of the multiple ornithine decarboxylase forms identified by ion-exchange chromatography of crude mammalian cell homogenates are related to enzyme conformation, the two major forms are distinctly charged protein states that can be visualized using two-dimensional gel electrophoresis of highly purified samples. PMID- 3341759 TI - Fluorescence of equine platelet tropomyosin labeled with acrylodan. AB - Equine platelet tropomyosin was labeled with the sulfhydryl-specific fluorescent reagent 6-acryloyl-2-dimethylaminonaphthalene (acrylodan). The extent of labeling at 4 degrees C could be regulated between 0.5 and 1.3 acrylodans per tropomyosin chain by varying the reaction time from 1 to 4.5 h. Acrylodan-labeled platelet tropomyosin, AD-P-TM, was highly fluorescent, having an emission maximum near 518 nm on excitation at 365 nm. Steady-state measurements of polarization of the fluorescence of AD-P-TM in both low and high ionic strength solutions gave Perrin plots that exhibited sharp changes in slope near 50 degrees C, indicative of a sharp increase in mobility of the label at that temperature. This correlates with the melting temperature of the platelet tropomyosin coiled coil observed by circular dichroism [G. P. Cote, W. G. Lewis, M. D. Pato, and L. B. Smillie, (1978) FEBS Lett. 91, 237-241]. Perrin plots of carboxypeptidase A-treated platelet tropomyosin that was labeled with acrylodan after digestion resembled more closely those of acrylodan-labeled cardiac tropomyosin rather than those of AD-P-TM, suggesting that the observed emission arose from label at Cys-153 on each truncated platelet tropomyosin chain. In solutions containing 150 mM KCl and 5 mM MgCl2, addition of actin at up to a sixfold molar excess over AD-P-TM caused both the fluorescence emission intensities and fluorescence polarization values of samples to increase. In the presence of actin, the wavelength of maximal emission was shifted to shorter values by about 5 to 7 nm. These changes indicate that actin does bind to AD-P-TM and that the binding affects the environment of the label, both by making it more hydrophobic and by reducing the freedom of the label to tumble in solution. PMID- 3341760 TI - Purification and characterization of an inducible aromatic amino acid-sensitive form of chorismate mutase from Solanum tuberosum L. tubers. AB - An amino acid-sensitive form of chorismate mutase (CM) has been purified over 1000-fold from disks excised from tubers of Solanum tuberosum L. cv White Rose. Purification was accomplished by chromatography on Matrix Blue A followed by affinity chromatography with tryptophan as ligand. CM assays performed in the absence of tryptophan yielded pH-dependent sigmoidal kinetics. At pH 8.0, sigmoidal kinetics were observed with a Hill coefficient of 1.66 (S0.5 = 188 microM). However, a shift from sigmoidal to hyperbolic kinetics was observed when assays were performed at pH 8.5. Addition of 9 microM tryptophan to the assay resulted in maximum activation of the enzyme with a Ka of 1.2 microM. When assayed in the presence of tryptophan, hyperbolic kinetics were observed over the pH range 6.0-8.0. Addition of tryptophan also decreased the Km for chorismate from 185 to 45 microM. Tryptophan (0.1 mM) completely protected CM from inhibition by phenylalanine (1.8 mM) and tyrosine (1.8 mM). However, in the absence of the activator, phenylalanine and tyrosine exhibited 50% inhibition at 0.80 and 0.68 mM concentrations, respectively. Both phenylalanine and tyrosine competitively inhibited CM activity with Ki values of 550 and 440 mM, respectively. Arogenate (1.0 mM) had no effect on CM activity in either the presence or absence of tryptophan. Analytical isoelectric focusing yielded an isoelectric point of 4.73. PMID- 3341761 TI - NADP-malate dehydrogenase from leaves of Zea mays: purification and physical, chemical, and kinetic properties. AB - NADP-malate dehydrogenase (NADP-MDH) from leaves of Zea mays has been purified and has a specific activity of 600-1000 mumol/min/mg protein. The native, inactive form of the enzyme is an 87.4-kDa, dimeric protein with a sedimentation coefficient of 5.5 S and a Stokes' radius of 3.62 nm. Isofocus analysis reveals the native enzyme preparation to contain two proteins of pI 4.88 and 4.90. The uv visible absorbance spectrum reveals no chromophores on the protein. The inactive form of the enzyme contains three thiols and three disulfides per subunit. 2 Mercaptoethanol can reduce two of the three subunit disulfides without concomitant activation of the enzyme. Treating the enzyme with dithiothreitol reduces all three subunit disulfides and fully activates the enzyme. These results show that NADP-MDH activation is dependent on the reduction of a critical disulfide bond. The enzyme can use both NADPH and NADH for oxaloacetate (OAA) reduction and NADP and NAD for malate oxidation at the following measured specific activities (eu/mg protein) at pH 8.5 in Tris buffer: NADPH plus OAA (690), NADH plus OAA (260), NADP plus malate (82), and NAD plus malate (37). These activities vary as a function of pH and buffer composition. Km values for the substrate pairs are NADPH (24 microM) plus OAA (56 microM); NADH (0.83 mM) plus OAA (61 microM); NADP (73 microM) plus malate (32 mM); and NAD (0.80 mM) plus malate (29 mM). The enzyme shows allosteric kinetics for NADP with a Hill number of 1.56. The enzyme is substrate-inhibited by malate for both NADP- and NAD-dependent activities. PMID- 3341762 TI - Hydrolysis of cis and trans isomers of retinyl palmitate by retinyl ester hydrolase of pig liver. AB - Relative retinyl ester hydrolase activities of pig liver homogenates (n = 4) toward 9,13-cis-, 13-cis-, 9-cis-, and all-trans-retinyl palmitate were 6.8 +/- 0.5 (SE), 5.7 +/- 0.5, 2.4 +/- 0.1, and 1, respectively. The range of apparent Km values for the four isomers was 142 to 268 microM, and the pH optima were 8-9 in all cases. Peak activities of retinyl ester hydrolase activities in pig liver cytosol toward 13-cis- and all-trans-retinyl palmitate were found in the 20 to 40% and in the 60 to 80% saturated ammonium sulfate (AS) fractions, respectively. By use of size-exclusion chromatography in 2 M KCl, hydrolase activity eluted at volumes corresponding to greater than 2000, 180, and 15 kDa from the 20-40% AS fraction, and at 180 kDa from the 60-80% AS fraction. On the basis of molecular size, different substrate specificities, detergent effects, and susceptibilities to inhibition by phenylmethylsulfonyl fluoride, we conclude that at least three distinct retinyl ester hydrolases are present in pig liver cytosol. PMID- 3341763 TI - Immunoaffinity purification of melanoma growth stimulatory activity. AB - Melanoma growth stimulatory activity (MGSA) is an endogenous growth factor produced by human malignant melanoma cells. When purified from conditioned medium from the Hs0294 human melanoma cell line, MGSA has been shown to be most reproducibly associated with a 16 kDa acid and heat stable moiety which is sensitive to trypsin and dithiothreitol. Monoclonal antibodies to MGSA have been produced. This report describes the use of FB2AH7 monoclonal antibody to prepare an immunoaffinity resin which binds the MGSA produced by Hs0294 cells. This resin was used to purify the MGSA antigen from Hs0294 human melanoma extracts and medium conditioned by the Hs0294 melanoma cell line. The immunoaffinity eluant obtained from both sources produced a significant stimulation in [3H]thymidine incorporation into DNA in Hs0294 cells and yielded similar profiles when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Upon elution of the material from the polycrylamide gels, a 16 kDa moiety was found to be more reproducibly active in the MGSA [3H]thymidine bioassay and enzyme-linked immunoadsorbent assay. The bioactivity of the 16 kDa material represents a 235,000-fold purification of MGSA. PMID- 3341764 TI - Limited proteolysis of inactive tetrameric chloroplast NADP-malate dehydrogenase produces active dimers. AB - Carboxy-terminal amino acids of NADP-dependent malate dehydrogenase (EC 1.1.1.82) from pea chloroplasts were removed by treatment with carboxypeptidase Y. This results in the activation of the inactive oxidized enzyme, while activation by light in vivo is thought to occur via reduction of an intrasubunit disulfide bridge. After proteolytic activation the oxidized enzyme had a specific activity of 100 U/mg protein, which is 50% of the maximal activity of the control enzyme in the reduced state. When the truncated enzyme was reduced with dithiothreitol (DTT), the specific activity was further increased to 1200 U/mg. While the native enzyme is composed of four identical subunits of 38,900 Da, the truncated malate dehydrogenase forms dimers composed of two subunits of 38,000 Da. No further change of molecular mass or activity was noticed subsequent to prolonged incubation of native NADP-malate dehydrogenase with carboxypeptidase Y for several days. When the enzyme is denatured by 2 M guanidine-HCl, the proteolytic activation proceeds more rapidly, but only transiently. The truncated enzyme is less accessible to activation by reduced thioredoxin, but the stimulation of activity by DTT alone is more rapid than that of the native enzyme. These results indicate that only a small carboxy-terminal peptide of native NADP-malate dehydrogenase from pea chloroplasts is accessible to proteolytic degradation and that this peptide is involved in the regulation of activity, tetramer formation, and thioredoxin binding. While the pH optimum for catalytic activity of the intact reduced enzyme is at pH 8.0-8.5, it is shifted to more acidic values upon proteolysis of NADP-malate dehydrogenase. At pH values below 8 the reduced truncated enzyme exhibits substrate inhibition by oxaloacetate. PMID- 3341765 TI - Purification of a manganese-containing superoxide dismutase from Halobacterium halobium. AB - An oxygen-induced superoxide dismutase was purified from the halophilic bacterium, Halobacterium halobium, strain NRL. Due to the high salt requirement for enzyme stability, the purification had to be performed in the presence of 2 M NaCl. The pI of the protein was 4.95. The approximate Mr was 38,500. The subunit size as determined by sodium dodecyl sulfate-electrophoresis was approximately 19,000. Metal analysis showed 1.5 atoms of manganese per dimer, 0.5 atom zinc, and 1.54 atoms copper. The N-terminal sequence of amino acids was determined, and based upon the first 26 amino acids significant homology to other manganese- and iron-containing superoxide dismutases was revealed. PMID- 3341767 TI - A preferential inhibition by Zn2+ on platelet activating factor- and thrombin induced serotonin secretion from washed rabbit platelets. AB - Zinc ions at micromolar levels exhibited a significant inhibitory activity toward platelet activating factor (AGEPC)- and thrombin-induced serotonin release from washed rabbit platelets. In the ranges from 25 to 30 microM and 10 to 50 microM, respectively, zinc essentially prevented any serotonin release from 1.25 X 10(8) cells/microliter by 1 X 10(-10) M AGEPC and by 0.2 unit thrombin/ml. This inhibition by zinc ions, in micromolar range, occurred in the presence of 1.0 mM Ca2+. The amount of zinc needed for inhibition was inversely proportional to the amount of AGEPC present and further zinc must be added prior to or at the same time as the AGEPC to be effective. Introduction of zinc ions after the AGEPC essentially abolished the inhibitory properties of this divalent cation. Other cations such as Cu2+, La3+, Cd2+, and Mg2+ were ineffective as inhibitors at concentrations where zinc showed its maximal effects. Under conditions similar to those noted above, aggregation induced by AGEPC was blocked only to the extent of 25% of a control. No inhibitory action by zinc on thrombin-induced aggregation was noted. It is apparent that zinc ions influence a site(s) on the rabbit platelet of considerable importance to the activation (or signaling) process by AGEPC and thrombin in these cells, as expressed by serotonin release. Zinc should provide a suitable probe to explore the mechanism of action of these agonists in their interaction with sensitive cells and to define in more specific biochemical terms the putative receptor for these molecules. PMID- 3341766 TI - Purification and kinetic and structural properties of spinach leaf NADP-dependent nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase. AB - NADP-dependent nonphosphorylating D-glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.9) from spinach leaves has been purified to apparent electrophoretic homogeneity by ammonium sulfate fractionation, molecular sieving on Sephadex G 200, DEAE-cellulose, and 2',5'-ADP-Sepharose affinity chromatography. The purified enzyme exhibited a specific activity of 15 mumol (mg protein)-1 min-1 and was characterized as a homotetramer with a native molecular weight of 195,000. Preincubation of the purified enzyme with NADP+ resulted in an almost twofold increase in enzymatic activity. The rate of activation was slower than the rate of catalysis, indicating that the enzyme has hysteretic properties. This behavior results in a lag phase during activity measurement of the enzyme preincubated without NADP+. Substrate interaction and product inhibition studies suggest a rapid equilibrium random BiBi mechanism for the reaction. Thiol modifying reagents, iodoacetamide and diamide, completely inactivated the purified enzyme. Inactivation by iodoacetamide exhibited pseudo-first-order kinetics with a rate constant of 0.17 min-1. D-Glyceraldehyde 3-phosphate effectively protected the enzyme against inactivation by thiol reagents, suggesting that modification occurred at or near the substrate-binding site. Complete inactivation of the dehydrogenase was correlated with incorporation of 8 mol [1-14C]iodoacetamide/mol enzyme. Total protection afforded by D glyceraldehyde 3-phosphate against enzyme inactivation by iodoacetamide was correlated with a protection of 4 mol reactive residues/mol enzyme. On the basis of these results it is suggested that one sulfhydryl group per enzyme subunit is essential for catalysis in spinach leaf nonphosphorylating glyceraldehyde-3 phosphate dehydrogenase. A kinetic and molecular mechanism for the reaction is proposed. PMID- 3341769 TI - The role of iron chelates on the selectivity of Fenton reagent in hydroxylation, N-demethylation, and sulfoxidation of cimetidine: a novel biomimetic model for the regioselectivity of cytochrome P-450. AB - The effect of iron chelates on the reaction of cimetidine with Fenton reagent [Fe(II)/H2O2] has been investigated. Iron chelates with high affinity to ferrous ions inhibited this reaction. However, iron chelates with high affinity to ferric ions selectively promote either hydroxylation, N-demethylation, or sulfoxidation of cimetidine. These results indicate that the oxidation of cimetidine with hydrogen peroxide activated by various chelated ferrous ions serves as a biomimetic model for the regioselectivity of multiple forms of cytochrome P-450 in the metabolism of cimetidine. PMID- 3341768 TI - Characterization of glutathione-dependent inhibition of lipid peroxidation of isolated rat liver nuclei. AB - Glutathione (GSH) is known to play an important role in protecting cells against oxidative stress. The present study was undertaken to assess the ability of GSH to protect isolated rat liver nuclei against NADPH-induced peroxidation. Nuclei were isolated from rat liver homogenates by discontinuous sucrose gradient centrifugation, and lipid peroxidation was induced by 1.7 mM ADP, 0.11 mM EDTA, 0.1 mM FeCl3, and either 1 mM NADPH or 0.5 mM ascorbate. The amount of lipid peroxidation was determined by measuring the formation of thiobarbituric acid reactive products and the disappearance of lipid unsaturated fatty acid moieties. The addition of GSH (0.1 to 1.0 mM) produced a concentration-dependent lag period prior to the onset of lipid peroxidation. This GSH-induced lag period was abolished by pretreatment of nuclei with trypsin, thiol modifying reagents, disulfides, or heating nuclei at 60 degrees C for 15 min. Nuclei which were incubated with GSH also catalyzed the conversion of cumene hydroperoxide to cumyl alcohol. Similarly, this activity was also inhibited by thiol modifying reagents, disulfides, and heating nuclei at 60 degrees C for 15 min. The data suggest that a GSH-dependent peroxidase activity is associated with rat liver nuclear membranes which are capable of inhibiting lipid peroxidation. PMID- 3341770 TI - NADPH-dependent microsomal metabolism of 14,15-epoxyeicosatrienoic acid to diepoxides and epoxyalcohols. AB - The arachidonic acid epoxygenase metabolite 14,15-epoxyeicosatrienoic acid is further metabolized by rat liver microsomal fractions to regioisomeric diepoxides and epoxyalcohols. Diepoxides result from epoxidation at the 5,6-, 8,9-, or 11,12 olefins. Hydroxylation leading to epoxyalcohols with a cis, trans-conjugated dienol occurs at carbons 5, 8, 9, or 12. Structural assignments were established by chromatographic and mass spectral comparisons with synthetic standards. The reaction requires NADPH and is inhibited by typical cytochrome P-450 inhibitors. Analysis of the time course of product formation during arachidonic acid oxidation by rat liver microsomal fractions indicated that all four regioisomeric epoxyeicosatrienoic acids can be further metabolized by the enzyme system. PMID- 3341771 TI - Purification and characterization of tryptophan dioxygenase from Streptomyces parvulus. AB - Tryptophan dioxygenase, derived from Streptomyces parvulus, was purified to near homogeneity and shown to have a native Mr of 88,000. Kinetic parameters of the enzyme were determined and evidence suggesting that it is a hemoprotein was obtained. Tryptophan dioxygenase has a high specificity toward L-tryptophan with an apparent Km of 0.3 mM. L-3-Hydroxykynurenine was a competitive inhibitor with respect to L-tryptophan with a Ki of 0.16 mM. In vitro, the enzyme displayed little activity in the absence of a reducing agent; ascorbate, at 50 mM, was the preferred reductant providing almost a 50-fold increase in enzyme activity. The regulation of tryptophan dioxygenase synthesis and activity is described. The expression of the enzyme is correlated with the biosynthesis of actinomycin D in S. parvulus. These results support the hypothesis that tryptophan dioxygenase functions as the first enzyme in the sequence converting L-tryptophan to the chromophore of this antibiotic. PMID- 3341772 TI - Circular dichroism of platelet factor 4. AB - The circular dichroism of platelet factor 4 was investigated and it was found to contain 15% alpha-helix, 25% beta-structure, and the rest of the molecule in unordered conformation. In the presence of heparin, no change in the circular dichroism was observed, suggesting no significant changes in the secondary structure of platelet factor 4 when heparin binds. The CD spectrum of platelet factor 4 was also investigated in the presence of increasing concentrations of guanidine hydrochloride. A two-state transition was observed with midpoints at 0.125 and 2.0 M guanidine hydrochloride. Based on gel filtration studies, the first unfolding transition was correlated with the dissociation of the tetrameric structure. This first unfolding domain was not observed in the presence of heparin, suggesting that heparin stabilizes the tetrameric structure. The second unfolding transition corresponds to the disruption of the overall secondary structure which is generally observed with most proteins. It is concluded that a relatively weak force of attraction holds the tetrameric structure of platelet factor 4 and the dissociation of the subunits is accompanied by loss of some helical secondary structure. PMID- 3341773 TI - A homolog of ribulose bisphosphate carboxylase/oxygenase-binding protein in Chromatium vinosum. AB - A 700-kDa protein composed of 12 apparently identical 60-kDa subunits copurifies with the L8S8 form of ribulose bisphosphate carboxylase/oxygenase (RuBisCO) from Chromatium vinosum. Chromatography on DEAE-Sephadex A-50 separates the two proteins in pure form. On the basis of the highly reproducible copurification and reaction of the 700-kDa protein with antibodies to pea RuBisCO large (L)-subunit binding protein, the protein from C. vinosum is designated as a putative binding protein (PBP) for RuBisCO. Also the N-terminal sequence of PBP is quite similar to that of both alpha and beta subunits of the L-subunit-binding protein. Our present research suggests that PBP may be a RuBisCO small-subunit-binding protein in C. vinosum. Measurements of RuBisCO activity and of species that immunologically cross react with RuBisCO or PBP (by enzyme-linked immunosorbent assay) establish that levels of the two proteins vary together in C. vinosum grown on different carbon sources. PMID- 3341775 TI - Purification of membranes and identification of phase-specific proteins of the dimorphic pathogenic fungus Histoplasma capsulatum. AB - Plasma membrane vesicles from the yeast and mycelial phases of Histoplasma capsulatum have been purified and characterized. The method of purification involved differential centrifugation of ballistically fractured cells followed by sedimentation through discontinuous sucrose density gradient and equilibrium centrifugation. Purity of the preparation was assessed by electron microscopy. The protein composition of the membrane preparations from the yeast and mycelial phases of the fungus was analyzed by polyacrylamide gels. A comparison of the two morphologic phases revealed quantitative and qualitative differences in the expressions of several membrane-specific proteins. Physical differences in the appearance of the membranes were also observed by electron micrography of membrane preparations. Alteration in membrane fluidity may be one of the many causes for differences in the appearance of membrane vesicles in the two phases. PMID- 3341774 TI - Superoxide dismutase induces differentiation in microplasmodia of the slime mold Physarum polycephalum. AB - Evidence is presented that supports a role for the enzyme superoxide dismutase (SOD) in the differentiation of the slime mold, Physarum polycephalum. SOD activity increases 46-fold during differentiation. A strain of Physarum that does not differentiate exhibits no change in SOD activity. Addition of SOD, via liposomes, to the nondifferentiating strain induces differentiation; this effect is enhanced by an inhibitor of glutathione synthesis. Other antioxidants selected for study failed to induce differentiation. Conversely, oxidative treatments including introduction of D-amino acid oxidase, via liposomes, induced differentiation. Cellular oxidation is the probable cause of the SOD effect. PMID- 3341776 TI - Calcium-dependent translocation of calbindin-D28k from intestine to blood. AB - Calbindin-D (vitamin D-induced calcium-binding protein; CaBP) is known to be present in blood at concentrations which vary directly with levels in the intestinal mucosa. Employing a sensitive radioimmunoassay and sampling mesentery venous blood, the present experiments demonstrated a direct relationship between intestinal calcium absorption and serum CaBP. Solutions containing 150 mM NaCl and 45Ca-labeled calcium chloride (5 or 20 mM) were placed in the lumen of ligated duodenal preparations in situ and mesentery venous blood sampled with time. The concentration of absorbed 45Ca in serum was maximal at 5 min, followed by a significant increase in mesentery CaBP maximizing at 15-20 min. Elevation of serum CaBP was not observed when calcium in the dosing solution was omitted or replaced by either glucose or glycine. The possible transfer of absorbed calcium from the enterocyte to the circulation as a CaBP complex was ruled out by calculations revealing that considerably more calcium was transferred than could be accounted for by the low and high affinity binding sites on the protein. It is proposed that vitamin D-dependent enhanced transcellular calcium transport constitutes a stimulus for the increased release of intestinal CaBP into the circulation. PMID- 3341777 TI - Purification of a peptidylglycine alpha-amidating enzyme from transplantable rat medullary thyroid carcinomas. AB - A peptidyl glycine alpha-amidating activity has been isolated from total tissue extracts of rat medullary thyroid carcinoma (MTC). Purification of the activity by ammonium sulfate fractionation, Sephacryl S-300 chromatography, and strong anion-exchange chromatography at pH 6.0 has resolved at least four peaks of activity. The activity associated with peak III has been further purified to apparent homogeneity by strong anion-exchange chromatography at pH 8.0. The purified peak III enzyme has an apparent molecular mass of 75,000 Da as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The identity of the 75,000-Da band as the alpha-amidating enzyme has been confirmed by recovery of activity from a nondenaturing polyacrylamide gel. The enzyme is catalytically active as a monomer, exhibits a pH optimum between 5.0 and 5.5, and has a turnover number of 300 min-1 for N-dansyl-Tyr-Val-Gly amidation at pH 5.5. The larger size, more acidic pH optimum, and higher specific activity distinguish the purified peak III rat MTC enzyme from the enzymes isolated from bovine and porcine pituitary or from frog skin. PMID- 3341778 TI - Modification of trypsin-solubilized cytochrome b5, apocytochrome b5, and liposome bound cytochrome b5 by diethylpyrocarbonate. AB - The interactions of diethylpyrocarbonate (DEP) with the various forms of cytochrome b5 were studied to gain a better understanding of the factors that influence the extent of modification of the axial histidines of cytochrome b5. Very low concentrations of DEP were able to decrease the heme binding capacity of apocytochrome b5. Moreover, it was shown that two additional histidines, presumed to be the axial ligands (His 39 and 63), were modified in the apo but not the holo form of a given preparation of cytochrome b5. Trypsin-solubilized bovine cytochrome b5 was resistant to the effects of DEP. A 200-fold molar excess of DEP displaced only 15% of the heme in the trypsin-solubilized protein in contrast to an 84% displacement of the heme in the detergent-solubilized protein. However, detergent-solubilized cytochrome b5 which had been incorporated into phospholipid vesicles exhibited the same reactivity with DEP as did the trypsin-solubilized protein. This is attributed to the fact that the two resistant preparations of cytochrome b5 are monomeric in their respective environments while detergent solubilized cytochrome b5 is known to exist as an octamer in aqueous solutions. Our studies suggest that dissociation of the octamer to the monomer results in a conformational change that decreases the reactivity of the axial ligands of the hydrophilic heme-containing domain of cytochrome b5. Examination of the cytochrome b5 molecule by computer graphics indicates that a tunnel leads from the surface of the molecule to axial histidine 63 and that axial histidine 39 is buried. PMID- 3341779 TI - Identification of latent procathepsins B and L in microsomal lumen: characterization of enzymatic activation and proteolytic processing in vitro. AB - Procathepsins B and L in the hepatic endoplasmic lumen were identified as having a molecular weight of 39,000 by immunoblot analysis. The proenzymes were then purified to remove the mature enzymes by concanavalin A-Sepharose chromatography. The concanavalin A-adsorbed fractions containing the proenzymes showed no appreciable activities of cathepsins B and L. When those fractions were incubated at pH 3.0, the enzymatic activities markedly increased: the activities of cathepsins B and L after 36 h incubation were 60 and 210 times those of the controls, respectively. Immunoblot analysis showed that after 36 h incubation the proenzymes disappeared and the mature enzymes increased. Thus the proenzymes were processed to the mature enzymes under acidic conditions of pH 3.0. The marked increases of enzymatic activities and the conversion of the proenzymes to the mature forms were completely blocked with pepstatin, which is a potent inhibitor of aspartic proteases. The results strongly suggested that a processing protease for procathepsins B and L might be cathepsin D, a major lysosomal aspartic protease. Indeed, lysosomal cathepsin D could convert microsomal procathepsin B to the mature enzyme in vitro. Therefore, procathepsins B and L seem first to be synthesized as enzymatically inactive forms in endoplasmic reticulum and successively may be converted into active forms by cathepsin D in lysosomal compartments. PMID- 3341781 TI - Multiwavelength method for measuring concentration of free cytosolic calcium using the fluorescent probe indo-1. AB - It is assumed that the spectra of fluorescent probes indo-1 and fura-2 in the cytoplasm are linear combinations of the spectra of calcium-bound and free probes with weight factors proportional to the concentrations of these forms. When the concentration of calcium is measured by the dual-wavelength method, the above assumption is employed without testing. A multiwavelength method for measuring free cytosolic calcium concentration is described in the present study. The method is based on the registration of the fluorescence spectra of the probe with an optical multichannel analyzer and deconvolution of the spectra into components, corresponding to free and bound forms of the probe. A mismatch is also calculated to allow estimation of deconvolution accuracy. It was found that the spectra, recorded in aqueous calibration solution with varying calcium concentrations, can be deconvoluted into components, obtained both in the absence of calcium and at its saturating concentration. When the spectrum of the probe in the cytoplasm is deconvoluted into the same components the mismatch is higher. When aqueous calibration is used, the cytosolic calcium concentration determined by the dual-wavelength method is dependent considerably on the selected wavelengths. Our data indicate that this phenomenon may be associated with the lower polarity of cytoplasm compared to the aqueous calibration solution. Addition of either ethanol or glycerol into the calibration medium results in a considerable decrease in the mismatch. The optimal concentration of ethanol is 22 32%, and depends on the type and condition of cells tested. It is shown that the use of calibration spectra obtained in aqueous solutions leads to considerable overestimation of cytosolic calcium concentration. PMID- 3341780 TI - Excitation energy transfer study of the spatial relationship between the carbonyl and metal cofactors in pig plasma amine oxidase. AB - 9-Hydrazinoacridine irreversibly labeled pig plasma amine oxidase by covalent attachment to the active carbonyl cofactor. The visible absorption spectrum of the modified protein displays new absorption bands at 495 and 525 nm. Its emission spectrum exhibited maxima at 415 and 440 nm. In addition, both absorption and emission spectra were insensitive to pH changes between 6 and 10. Phase modulation fluorometry was used to determine fluorescence lifetimes of Zn2+ and Co2+-substituted acridinyl plasma amine oxidase. Energy transfer efficiency was 22%; the distance separating the Co2+ ion (in the copper binding site) and the acridine moiety (the amine substrate binding site) ranges between 11.7 and 14.7 A. This work defines the proximity of the metal and substrate (and hence the carbonyl cofactor) and precludes any direct interaction between Cu2+ and pyrroloquinoline quinone or between Cu2+ and the substrate. PMID- 3341782 TI - [Current status of the treatment of urothelial tumors]. AB - Cancer of the urinary bladder, renal pelvis and ureter is usually transitional cell carcinoma. One third of cases of urethral cancer are also transitional cell carcinoma. In planning the treatment for these urothelial cancers, the anatomic stage (Ta-T4), the histologic grade (1-3), tumor multiplicity and tumor size are generally taken into account. Superficial and low-grade tumors can usually be treated by transurethral resection. However, such patients run the risk of subsequent tumor recurrence in the bladder. This risk may be reduced by intravesical administration of anti-neoplastic agents and BCG. Diffuse carcinoma in situ (CIS) should be treated intravesically before deciding on surgical extirpation of the bladder. Patients with tumors showing deep muscle invasion are usually managed by surgery. The role of adjuvant chemotherapy and/or radiation therapy is currently under investigation. Patients with unresectable cancer and/or metastases are candidates for systemic chemotherapy. This form of therapy is now resulting in an increased number of complete and partial remissions. However, there is still no evidence that systemic chemotherapy prolongs the duration of survival, especially in patients showing partial remission. PMID- 3341783 TI - [Treatment of prostatic cancer]. AB - Since more than half of stage A-C prostatic cancers show pelvic lymph node metastasis (D1, pN1-3), a staging operation is required at the start of treatment. Most pN0 and pN1 (stage A2BC) cases have been treated with radiation, and good results have been obtained. Endocrine therapy, consisting of orchiectomy and immediate administration of a large dose, followed by an intermediate dose of estrogen or antiandrogen, was applied to pN2-4 and D2 cancer cases. Five-year survival was approximately 40%, and side effects were less marked than those reported in western countries. Factors affecting prognosis during endocrine therapy were grade, acid phosphatase response, and tissue androphilic protein. For D2 with risk factors, chemoendocrine therapy was applied, but no improvement in survival was observed. PMID- 3341784 TI - [Current therapy of endocrine organ tumors (adrenal and parathyroid glands)]. AB - Since the adrenal or parathyroid cancer is a clinically rare entity. We often have difficulty in its diagnosis and treatment. The adrenocortical cancer is usually classified into two categories--endocrinologically functioning or non functioning. The incidence is not different between them. It is often found in an advanced stage as it does not show clinical manifestation before it has grown up to a large tumor. Only an effective agent for the adrenal cancer is op'-DDD so far. Recently, cisplatin, VP-16 (etoposide) and others are administered as trial use. Most of malignant pheochromocytomas are endocrinologically active and they often cause hypertension leading to death. Therefore it is important to control hypertension in malignant pheochromocytoma. Chemotherapy and irradiation are not effective for it. Recently, 131I-MIBG (metaiodobenzylguanidine) is found to be useful not only for diagnosis but also treatment of malignant pheochromocytoma. 131I-MIBG is accumulated specifically in the chromaffin cells and with helpful to find out metastatic foci. It is also used in a large amount as a specific irradiation therapy for this malignancy. Parathyroid cancer is found in approximately 3 percent of primary hyperparathyroidism. Clinically it usually reveal serum calcium level higher than 14 mg/dl, bone lesions and renal dysfunction in addition to palpable cervical tumors adhering with skin. Sometimes it is difficult to differentiate malignancy from adenoma in histology. Most cases develop local recurrences and distant metastases in due course and dies of hypercalcemia. It is very important to control hypercalcemia in inoperable cases. As both chemotherapy and radiation therapy render no effect on this malignancy. Surgery is a sole strategy for it. PMID- 3341786 TI - [Study on changes in plasma platinum concentrations after administration of CDDP to maintenance hemodialysis patients]. AB - Changes in plasma platinum concentration after administration of CDDP were studied in six patients on maintenance hemodialysis with malignancies. Plasma exchange was carried out on three patients for the purpose of plasmapheresis. A therapeutic dose of 51 mg/m2 of CDDP was administered to each patient without any severe adverse reactions. Plasma platinum concentration was measured by atomic absorption spectrophotometry, and the decay curve of the agent showed a biphasic pattern with an initial steep alpha phase and an ensuing mild beta phase in both hemodialysis patients and normal controls. As these patterns showed no renal excretion of CDDP, it was suggested that the uptake of CDDP into tissue was one of the main causes of the steep alpha phase. In patients given plasma exchange one or two hours after the beginning of CDDP administration, the reduction rates of plasma platinum were 74.7-61.7%, but the collection rate of the agent in the exchanged plasma was only 22.2-7.5%. These results indicated that the uptake of CDDP into tissue might occur rapidly within a few hours after CDDP administration. PMID- 3341787 TI - [Antitumor effect of cepharanthin--mechanism of the antimetastatic effect on Lewis lung carcinoma (3LL)]. AB - The antitumor activity of cepharanthin against Lewis lung carcinoma (3LL) primary tumor and its pulmonary metastases was evaluated. Oral administration of cepharanthin to tumor-bearing mice at a daily dose of 5 mg/kg resulted in inhibition of 3LL primary tumor growth, preferential suppression of pulmonary metastases, and prolongation of survival time. The antimetastatic effect was not observed when tumor-bearing mice were treated with some blockers of immunocompetent cells, e.g. carrageenan or monoclonal anti-Thy 1.2 antibody. In ex vivo experiments, cepharanthin was also shown to augment the activities of murine alveolar macrophages and splenic natural killer (NK) cells. These results suggest that the antitumor or antimetastatic effect of cepharanthin might be expressed through host defense mechanisms, including macrophages, T lymphocytes and/or NK cells. PMID- 3341785 TI - [Local administration of recombinant interferon-beta to patients with cancer associated body cavity fluids]. AB - The effects of local administration of interferon-beta produced by recombinant DNA technology (GKT-beta, Kyowa Hakko) on malignant effusion were studied in cancer patients and evaluated on the basis of the Criteria for the Evaluation of the Clinical Effects of Solid Cancer Chemotherapy (effects on malignant effusion). Out of 13 cases of peritoneal effusion, the effects were evaluated in 9 cases. Four of these cases remained free from ascites for 4 weeks and were evaluated as complete response (CR). Administration of GKT-beta alone was performed in 4 of 7 cases of pleural effusion, and CR was obtained in 1 case each of breast cancer, gastric cancer and malignant mesothelioma. In cases of gastric cancer, CR was obtained in 5 of 10 cases. The above results suggest that GKT-beta is a very effective drug against malignant effusion. PMID- 3341788 TI - [Preoperative intra-arterial infusion of adriamycin in advanced breast cancer with reference to estrogen receptor status]. AB - Preoperative intra-arterial infusion of adriamycin [I I A] for advanced breast cancer was performed in 22 cases, and correlation of the estrogen receptor (ER) status with the effect of I I A therapy was histologically examined. Fifty-five percent of all cases responded to I I A; 80% of ER-negative cases responded, whereas only 33% of ER-positive cases did. I I A was significantly effective in ER-negative cases (p less than 0.05). The histological effect of I I A was also remarkable in ER-negative cases and was related to the clinical effect. The ER status was thought to be a parameter not only for hormonal therapy, but also for chemotherapy. Additionally, drill biopsy was performed in order to examine the correlation between the therapeutic effect and histological type in 16 cases before I I A therapy. Scirrhous carcinoma was more responsive to the I I A therapy than other histological types. PMID- 3341789 TI - [Platinum concentrations in human tissue after administration of cisplatin]. AB - Using flameless atomic absorption spectrophotometry, platinum concentrations in tissue samples were determined to clarify the distribution and accumulation of platinum in the human tissue after administration of cisplatin. Tissue samples were obtained at the time of autopsies or operation from 14 patients who were given cisplatin 0.7-20.1 mg/kg. Platinum concentrations were highest in the liver and testicle, high in the kidney, lung, heart and spleen, and lowest in the brain. In most organs except the brain, the tissue platinum concentrations increased exponentially according to the total dose of cisplatin. Platinum concentrations in metastatic tumors were generally somewhat lower than those in the normal parts of the organs, with the exception of cerebral metastasis. However, some of the metastatic tumors in the lung and brain showed higher concentrations than those in normal parts of the lung and brain, respectively. PMID- 3341790 TI - [Prevention of immunodeficiency induced by cancer chemotherapy with BCG]. AB - MFC (MMC, 5-FU and cytosine-arabinoside) therapy applied with the liver organism Bacillus Calmette-Guerin (BCG) for the treatment of postoperative patients with cancer of the digestive organs presenting at stage II and III. Immunological parameters included skin reaction by purified protein derivative (PPD), lymphatic blastogenesis test using phytohemagglutinin (PHA) and lymphatic subsets. The frequency of MFC therapy was significantly higher in the MFC plus BCG group than in the MFC group (p less than 0.001). At the completion of MFC therapy, both of PHA blastogenesis rate, OKT4/OKT8 and OKT3 were all within the normal limits. The PPD skin reaction was positive (18.2 +/- 4.0mm) as before the start of MFC therapy. These results suggest that BCG immunotherapy may potentiate the effect of chemotherapy. PMID- 3341791 TI - [Combination use of lentinan with X-ray therapy in a mouse experimental tumor system (Part I). Basic studies]. AB - Apparent reduction of leukocyte counts was observed in mice irradiated with 1,500 approximately 3,000 rads of X-ray on the left hind leg. This reduction of leukocyte counts was completely protected by the pre-treatment with lentinan before X-ray irradiation. Suppressive effect of X-ray on the antitumor function of lentinan seems to be weak. When treatment with X-ray irradiation and lentinan was applied for mice bearing solid type sarcoma 180, additive effect was obtained by the combination of lentinan before or after X-ray irradiation. PMID- 3341793 TI - [A case of bronchial carcinoma showing regression upon intratumoral administration of OK-432]. AB - A 38-year-old female suffering from chronic respiratory symptoms due to lung cancer occupying the left main bronchus was treated by frequent intratumoral injections of OK-432. The immune-modifying therapy was performed as follows; 0.2 KE of OK-432 was injected intracutaneously once a week, then the dose was gradually increased to 3.0 KE once a week. Following immunization, intratumoral injection was done under endoscopy at a dose of 3.0 KE every two weeks. Three months later, the tumor showed remarkable regression, and clinical symptoms were diminished. In conclusion, intratumoral injection of OK-432 was considered to be very beneficial in lung cancer. PMID- 3341792 TI - [Studies of 5-FU concentrations associated with microangiography in colorectal cancer tissue]. AB - In order to elucidate the effect of supplying vessels on 5-FU distribution within a tumor, the correlation between 5-FU tissue concentration and tumor microangiography was examined in 31 patients with colorectal cancer after administration of 5-FU (500 mg/day for 3 days). The 5-FU concentration at the tumor margin was significantly higher than that in the other two tissue areas (p less than 0.05). A low 5-FU concentration was noted in the central region of ulcerative cancer showing vertical invasion with vascular disarray and/or histological necrotic foci. This type of tumor also showed a low RNA index by flow cytometry. The present study indicates that the vascular change and vascular pattern of a tumor may be a major contributing factor to 5-FU transfer from the blood circulation into a tumor. PMID- 3341794 TI - [Clinical application of calcitonin in giant cell tumor of the bones]. PMID- 3341795 TI - Topical fibronectin therapy for treatment of a patient with chronic stasis ulcers. PMID- 3341797 TI - Allergic contact dermatitis to gold. PMID- 3341796 TI - Fish oil consumption reduces hypertriglyceridemia in psoriatic patients receiving etretinate therapy. PMID- 3341798 TI - Surgical ligation of dilated external carotid artery improves associated port wine stain. PMID- 3341799 TI - Chondrodermatitis helicis arising after radiation therapy. PMID- 3341801 TI - Clinical and histologic heterogeneity of psoriatic plaques. Therapeutic relevance. AB - Twenty-three patients with resistant psoriasis vulgaris were evaluated clinically and histologically before and after treatment with potent topically administered steroids. It was shown that psoriatic plaques are comprised of clinically and histologically distinct acute and chronic areas, each responding differently to treatment. Chronic areas, characterized by chronic inflammation, respond well to therapy; acute areas, characterized by acute inflammation, are resistant to therapy. It is suggested that the psoriagenic stimulus is greater within the therapy-resistant "hot spots." Future therapy aimed at hot spots may aid in the better control of psoriasis. PMID- 3341800 TI - In vitro and in vivo antistaphylococcal activity of human stratum corneum lipids. AB - Despite the assumption that sebum-derived fatty acids are responsible for cutaneous antimicrobial defense, no studies have assessed the contribution of epidermis-derived lipids. Herein, we tested the antistaphylococcal effects of human stratum corneum lipids, enriched in endogenous, keratinocyte-derived species obtained by lipid extraction and thin-layer chromatography, for antimicrobial activity in both in vitro and in vivo systems. Whereas the most potent species in vitro were the free fatty acids, polar lipids and glycosphingolipids also demonstrated antistaphylococcal activity in vitro, while other neutral lipids displayed virtually none, results that were confirmed with authentic standards in vitro. In a pilot study on delipidized forearm test sites in human volunteers, naturally occurring free fatty acids, polar lipids, and glycosphingolipids exhibited significantly more antistaphylococcal activity than other stratum corneum lipids or vehicle controls. Finally, biopsy specimens of incubated skin sites demonstrated penetration of staphylococci through lipid enriched intercellular domains. These results provide the first evidence that endogenous, epidermis-derived skin lipids may contribute to cutaneous antimicrobial resistance. PMID- 3341802 TI - Fibronectin enhances healing of excised wounds in rats. AB - Fibronectin (Fn) is a normal plasma and extracellular matrix glycoprotein that is involved in each phase of wound healing. For example, it is incorporated into both fibrin and collagen fibers; it opsonizes circulating tissue debris for removal by the reticuloendothelial system; it is used by macrophages, fibroblasts, and epithelial cells to move into the wound; and fragments of Fn are chemotactic for fibroblasts. In this study, experiments with rats showed that excised lesions treated with Fn healed more rapidly than paired control lesions treated with the carrier alone. Applications of Fn once a day for two days were as effective in speeding healing as twice-daily applications of Fn for 12 days. A single treatment with Fn soon after the initial injury was nearly as effective as more prolonged treatment regimens. PMID- 3341803 TI - Tissue debris at the injury site is coated by plasma fibronectin and subsequently removed by tissue macrophages. AB - Fibronectin (Fn) is a normal plasma and extracellular matrix glycoprotein that is thought to be important in reticuloendothelial system function as well as in promoting adhesion of various cell types to basement membranes and to each other. Plasma Fn levels are depressed following almost any type of trauma. It opsonizes circulating tissue debris for removal by the fixed cells of the reticuloendothelial system. It has been assumed but not proven that Fn also opsonizes tissue debris at the site of the injury for subsequent phagocytosis by tissue macrophages. In this study, rats were given intracardiac injections of Fn coupled with fluorescence isothiocyanate (Fn-FITC) and human serum albumin rhodamine isothiocyanate (HSA-RITC). Abdominal Rebuck skin windows were then prepared. Within 24 hours, debris at the sites of injury were observed to be coated with Fn-FITC but not HSA-RITC. This Fn-labeled debris was subsequently ingested by macrophages at the site. No macrophages were found that had taken up HSA-RITC. Thus, Fn is seen to coat tissue debris and effete cells within the wound, and the coated material is subsequently removed by tissue macrophages. PMID- 3341804 TI - Delayed pressure urticaria histologically resembles cutaneous late-phase reactions. AB - In a recent study, all patients with delayed pressure urticaria (DPU) developed late cutaneous reaction (LCR) after intradermal injection of compound 48/80 and after skin testing with certain food antigens. In the present study, we analyzed the histologic changes in the pressure lesions and compared them with those found in normal skin injected with diluent and in LCR to 48/80. The study included five patients with DPU associated with chronic urticaria (CU) and four patients with CU but without DPU. Six to eight hours after pressure challenge and intradermal skin testing with 48/80 and diluent, skin biopsy specimens were obtained from the pressure lesions, the LCRs, and normal skin (diluent injection). Specimens were assessed by Giemsa staining of 1-micron sections and immunofluorescence of frozen sections. Total cells were counted in each specimen. Interstitial deposits of fibrin were observed by immunofluorescence in LCR and pressure lesions. The total numbers of infiltrating cells in the dermis among LCR sites and pressure lesions were not significantly different, while both LCR sites and pressure lesions contained significantly more infiltrating cells than did normal skin injected with saline diluent. The differential counts in LCR and DPU were mostly mononuclear cells. Infiltrates in the DPU and LCR were mostly perivascular. No histopathologic changes were seen at skin sites challenged with pressure in the control patients with CU without clinical manifestations of DPU. We conclude that lesions seen in DPU are morphologically similar to classic LCR. PMID- 3341805 TI - No apparent neurologic defect in a patient with xeroderma pigmentosum complementation group D. AB - A 31-year-old female patient with xeroderma pigmentosum (XP) XP43KO was assigned to complementation group D by the cell-fusion complementation methods. Cultured XP43KO cells from our patient had the defective DNA repair phenotype showing a residual level of ultraviolet (UV)-induced unscheduled DNA synthesis (45% of normal) and an eightfold higher sensitivity to 254-nm UV killing, compared with normal cells. The phototest on the patient revealed the delayed maximum reaction to UV-B-induced erythema and lower minimal erythema doses at 290- and 300-nm monochromatic wavelengths. However, the XP43KO patient showed no apparent neurologic abnormalities and rather mild or moderate skin lesions at the age of 31 years, although DNA repair deficiency in XP43KO cells from our patient fell into the range of group D cells. PMID- 3341806 TI - Consort contact dermatitis due to oak moss. AB - An allergic contact dermatitis in a woman was found to be due to oak moss in her husband's after-shave lotion. When routine patch testing reveals a positive reaction, the dermatologist should consider exposure to the antigen not only in the patient but also through contact with the patient's consort. PMID- 3341808 TI - Flesh-colored nodule on the forearm. Intravascular papillary endothelial hyperplasia (IVPEH). PMID- 3341809 TI - Chronic zosteriform eruption of the lower extremity. Lymphangioma circumscriptum (LC), localized form. PMID- 3341807 TI - Purple nodules on the lower extremity following above-knee amputation. Angiosarcoma. PMID- 3341810 TI - Reddish-blue hands and feet. Acrocyanosis with atrophy. PMID- 3341811 TI - Continuing the means-ends discussion from the history of science. PMID- 3341812 TI - Surgical versus endoscopic management of common bile duct stones. AB - The charts of all patients with common bile duct (CBD) stones admitted to Virginia Mason Medical Center between January 1, 1981 and July 31, 1986 were reviewed to define current methods of management and results of operative versus endoscopic therapy. Two hundred thirty-seven patients with CBD stones were treated. One hundred thirty patients had intact gallbladders. Of these patients, 76 (59%) underwent cholecystectomy and common bile duct exploration (CBDE) while 54 (41%) underwent endoscopic papillotomy (EP) only. Of the 107 patients admitted with recurrent stones after cholecystectomy, all but five were treated with EP. The overall mortality rate was 3.0%. Complications, success, and death rates were all similar for CBDE and EP, but the complications of EP were often serious and directly related to the procedure (GI hemorrhage, 6; duodenal perforation, 5; biliary sepsis, 4; pancreatitis, 1). Patients undergoing EP required significantly shorter hospitalization than those undergoing CBDE. Multivariate analysis showed that age greater than 70 years, technical failure, and complications increased the risk of death, regardless of procedure performed. Twenty-one per cent of those undergoing EP with gallbladders intact eventually required cholecystectomy. The conclusion is that the results of EP and CBDE are similar, and the use of EP has not reduced the mortality rates of this disease. PMID- 3341814 TI - Risk factors in relation to postoperative complications in patients undergoing esophagectomy or gastrectomy for cancer. AB - To clarify the risk factors contributing to postoperative complications in the elderly patients (over 70 years) undergoing esophagectomy and/or gastrectomy, 364 patients with primary cancer seen were evaluated. As a result, some characteristic patterns of stress response in the elderly could be detected as follows: the disorders of the vital organs were more important indices for the development of postoperative complications rather than age, and a reduction in the maximum response of the stress hormones to surgical procedures in aged patients was noted; moreover, the functional variability of target organ in the aged group was confirmed. Studies on the hormonal response to surgery suggest that the restriction of fluid replacement is advisable until the third postoperative day, maintaining the host on the dry side, to prevent cardiopulmonary complications. As the nutritional status in the patients with esophageal and gastric cancer goes from bad to worse with the advancing clinical stages, adequate perioperative nutrition is imperative to prevent complications such as anastomotic leakage, wound dehiscence, and/or infections. For the treatment of anastomotic leaks after esophagectomy and esophagogastrectomy, more than 45 kcal/kg/d must be provided, and the serum albumin level must be restored to 3.5 g/dL in order to achieve spontaneous healing of small anastomotic leakages. PMID- 3341813 TI - Reoperation for congenital choledochal cyst. AB - A reoperation after excisional procedure was carried out in seven cases due to early or late postoperative complications. Of the 12 patients with early complications, four underwent relaparotomy due to anastomotic leakage and bleeding. Late complications were seen in nine patients with recurrent cholangitis caused by an anastomotic stricture, and three patients with intrahepatic involvement required a reoperation several years after the initial surgery. Recurrent cholangitis after biliary reconstruction mainly occurs due to an anastomotic stricture of the hepaticoenterostomy. There was no significant difference in the results between hepaticoduodenostomy and hepaticojejunostomy over a long follow-up period. A wide anastomotic stoma that permits free drainage of bile into the intestine is imperative to the prevention of cholangitis, and can be created by an incision extending along the lateral wall of both the hepatic ducts with a hepaticoenterostomy at the hilum. This procedure is obviously necessary in all patients with or without intrahepatic involvement. Carcinoma of the intrahepatic ducts and the retained distal choledochus have rarely developed in patients undergoing cyst excision followed by biliary reconstruction. Complete excision of the whole extrahepatic bile duct could prevent carcinoma arising in the distal choledochus, although it could not prevent carcinoma arising from the intrahepatic ducts. However, patients with carcinoma of the intrahepatic duct were reported to have had symptoms of biliary stricture for a long time since the cyst excision. Bile stagnation in the intrahepatic ducts is possibly responsible for the development of carcinoma. A wide anastomosis resulting in free drainage of bile appears to be essential to the prevention of carcinoma arising in the intrahepatic ducts after cyst excision. PMID- 3341815 TI - Colonoscopic detection of early colorectal cancers. Impact of a surgical endoscopy service. AB - The Surgical Endoscopy Service has been aggressively evaluating gastrointestinal symptoms with colonoscopy and screening asymptomatic patients with flexible sigmoidoscopy in hopes of finding early curable colorectal cancers. The purpose of this study was to compare the stages of colorectal cancers resected during the 18-month period prior to (Pre-SES) and during the first 18 months (Post-SES) after the creation of the Surgical Endoscopy Service. In addition, the yield of lesions that would have been obtained by depending upon patient symptoms or occult blood testing were determined. A total of 361 colonoscopies were performed Pre-SES and 874 colonoscopies Post-SES; 26 patients underwent resection of colorectal cancers Pre-SES and 32 Post-SES. Whereas early colorectal cancers (Dukes' A and B1) were found in only three patients (12%) Pre-SES period, early cancers were found in 13 (41%) Post-SES. Doubling the number of colonoscopies produced a fourfold increase in the number of early lesions. Furthermore, disseminated cancers (D lesions) dropped from 19% Pre-SES to 3% Post-SES. Among the total 58 patients, 43% of the A lesions and 40% of the B1 lesions were asymptomatic. Even more alarming, 86% of the A lesions, 50% of the B1 lesions, 31% of the B2 lesions, and 14% of the C2 lesions were occult blood negative. Indeed, only the D lesions were uniformly occult blood positive. This study demonstrates that aggressive colonoscopy detects early colorectal cancers. Moreover, patient symptoms or occult blood testing will fail to indicate the majority of early colorectal cancers. PMID- 3341816 TI - In situ tibial reconstruction. State-of-the-art or passing fancy. AB - To further evaluate the efficacy of in situ saphenous vein bypass, the authors have reviewed their experience with in situ bypass. Between October 1981 and December 1985, 120 in situ saphenous vein bypass were performed; 81 were to infrapopliteal vessels. All procedures were performed for limb salvage. The mean patient age was 74 years, and 74% were men, 57% had diabetes mellitus, 92% were smokers, and 72% had hypertension and/or coronary artery disease. All patients were evaluated by preoperative noninvasive testing and biplanar angiography. All procedures were performed by the valve incision technique. The vein utilization rate was 91%. Grafts were routinely placed into isolated tibial segments and foot vessels without evidence of a patent pedal arch. Follow-up information was obtained at 3-month intervals. Patency and limb salvage data were calculated by life-table analysis. The cumulative patency rates were 98% at 1 month, 88% at 12 months, and 82% at 50 months. These data demonstrate that the in situ bypass maintains an excellent patency rate and provides durable limb salvage. PMID- 3341818 TI - Results of surgical correction of anorectal malformations. A 10-30 year follow up. AB - Of 119 patients with surgical correction of anorectal malformations, 47 who were 10-30 years of age were interviewed personally and had manometric studies to evaluate postoperative continence. This clinical study included not only long term anorectal function but also sexual function. Patients with low type anomalies or with intermediate type anomalies were more likely to be continent, whereas patients with high type lesions had some problems with continence. However, only two of the 16 patients (12%) with high type anomalies were classified as having poor results. This rate is perhaps lower than might be expected. Thus, incontinent patients may become continent even if they were classified as having fecal incontinence before 6 years of age. Most patients who were 15-30 years of age had normal sexual function except for two females with irregular menstruation. These results indicate that achievement of fecal continence and sexual function in patients with high type anomalies treated by abdominoperineal rectoplasty depends on careful dissection as close as possible to the rectal wall and bringing the terminal bowel down exactly within the sling of the puborectal muscle. PMID- 3341819 TI - There is life outside the operating room. PMID- 3341817 TI - The patient's appraisal of the cosmetic result of segmental mastectomy in benign and malignant breast disease. AB - Women's appraisal of the cosmetic result and their psychosocial adjustment after a standardized segmental mastectomy for benign or malignant breast disease was analyzed on the basis of a mailed questionnaire, which was satisfactorily answered by 263 (92%) of 285 women operated on consecutively. The overall result was favorable: 96.5% of the patients found the new appearance of their breast very good (30.7%), good (44.0%), or acceptable (21.8%). Women with a benign diagnosis ran a two-fold higher risk of being discontented with the new appearance of the breast than those with breast cancer. Complications of radiation therapy, preoperative concern that the breasts are important for the appearance, and anxiousness about the cosmetic result were associated with a significantly elevated risk of being less satisfied with the outcome. The main finding that it is possible to perform a locally radical operation that is highly acceptable to the woman is relevant to the surgical management of potentially malignant mammographic lesions and also to the scientific strategies for future evaluation of breast-conserving treatment modes in malignant disease. PMID- 3341820 TI - Long-term results of mitral valve surgery in patients with severe pulmonary hypertension. AB - Mitral valve surgery was performed in 88 patients with severe pulmonary hypertension (average systolic pulmonary artery pressure, 94.7 +/- 22 mm Hg; range, 70-180 mm Hg) over a 10-year period. Sixty-four patients (73%) were in New York Heart Association Functional Class III or IV. There were 64 valve replacements and 24 open mitral commissurotomies. Operative mortality was 5.6% (5 patients) and was not related to the degree of pulmonary hypertension, surgical procedure performed, or type of valve lesion. A 100% follow-up was obtained, ranging from nine months to 10 years, with a mean of 44 months. Six late cardiac deaths (7.2%) occurred, 5 in patients with valve replacement and 1 in a patient who underwent a commissurotomy. Actuarial survival was 86 +/- 3% at five years and 83 +/- 4% at 10 years. Fourteen patients underwent right ventricular catheterization a mean of 24 months following operation. Systolic pulmonary artery pressure had decreased from a mean preoperative value of 101 +/- 22 to 40.5 +/- 7 mm Hg (p less than 0.001). Cardiac index increased by 55% of the preoperative values. Functional status improved markedly; 71 survivors (93%) were in New York Heart Association Class I or II. These results indicate that, in patients with mitral valve lesions and severe pulmonary hypertension, (1) surgical procedures can be performed with an acceptable operative mortality; (2) excellent long-term survival and functional results can be obtained; and (3) pulmonary hypertension decreases significantly after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341821 TI - Surgical management of esophageal strictures. AB - The cases of 50 consecutive patients requiring operative treatment for esophageal strictures were reviewed to evaluate results and develop principles of management. Forty-eight had gastroesophageal reflux disease and 2 had chronic lye strictures. Of the patients with gastroesophageal reflux disease, 21 had a Barrett's esophagus. Esophageal dilations had been performed in 29 patients, 12 of whom also had undergone previous surgical procedures. Preoperative dilations by our group were used to determine further intervention. Patients with dilatable strictures were randomized to either a Nissen or a Belsey operation. In this group, there were no operative deaths, and excellent or good clinical results were obtained in 28 of 34 (82%) patients, with no significant differences noted in the outcomes between the two operations. Patients with undilatable strictures, Barrett's ulcer, or mucosal dysplasia underwent resection plus colon interposition (N = 12) or resection plus gastric interposition (N = 4). Two of the patients in the Nissen operation group later required resection and colon interposition, bringing that total to 14. Resection plus colon interposition resulted in excellent or good results in 71% of patients, with a 7% operative mortality. These results suggest that a standard transthoracic antireflux procedure can be performed with a low risk when strictures are dilatable. Excellent or good results were obtained in 82% of patients, which is equivalent to results for more complex operations. There was no significant difference in the outcome for the transthoracic Nissen procedure compared with the Belsey procedure. In addition, when required, resection plus colon interposition provided excellent or good results in 71% of the patients. PMID- 3341822 TI - Suppressive effect of ulinastatin on plasma fibronectin depression after cardiac surgery. AB - Plasma fibronectin, an opsonic glycoprotein, is known to modulate the reticuloendothelial phagocytic clearance of nonbacterial and, possibly, bacterial particulates. The decreased plasma fibronectin levels seen after cardiac surgery have been considered to derive mainly from opsonic consumption. In the present study, we demonstrated that the administration of ulinastatin, a human urinary trypsin inhibitor, to patients after cardiac surgery not only inhibited the postoperative depression of plasma fibronectin levels, but also maintained the plasma fibronectin level within the normal range. This effect apparently resulted from the inhibitory activity of ulinastatin on the proteolytic enzymes released after operation. This result suggests that the decreased plasma fibronectin level noted after cardiac surgery may derive mostly from excessive proteolytic enzymes. Our observation also indicates that the prophylactic administration of ulinastatin to patients undergoing major operations will result in a favorably functional reticuloendothelial phagocytic system. PMID- 3341823 TI - Coarctation of the aorta in infants: which operation? AB - In this series, 178 infants (age, less than or equal to 3 months old) underwent repair of aortic coarctation. Pure coarctation was present in 63 patients (Group 1), 47 infants had additional ventricular septal defects (Group 2), and 68 patients had associated complex heart disease (Group 3). Subclavian flap angioplasty was used in 26 patients, limited resection and end-to-end anastomosis in 45 patients, extended resection and end-to-end anastomosis in 99 patients, and miscellaneous procedures in 8 infants. The early mortality was 8% for the first group, 11% for the second group, and 37% for the third group (p less than 0.001). Mean follow-up was 32 months and included 97% of patients. Actuarial survival at five years was 90% for the first group, 84% for the second group, and 40% for the third group. Recoarctation occurred in 15 operative survivors (11%); 7 necessitated reoperation. Freedom from recoarctation at five years was 89% after subclavian flap angioplasty, 81% after end-to-end anastomosis, and 86% following extended resection and end-to-end anastomosis. Early mortality and late results were not influenced by the type of coarctation repair but were determined by the clinical status and the presence of associated major cardiac anomalies. These results suggest that the surgical procedure should be individualized for each infant to optimize the aortic anatomy. PMID- 3341824 TI - Effect of the Trendelenburg position on the distribution of arterial air emboli in dogs. AB - We examined the effects of buoyancy on the distribution of arterial gas bubbles using in vitro and in vivo techniques in dogs. A simulated carotid artery preparation was used to determine the effects of bubble size and vessel angle on the velocity and direction of bubble movement in flowing blood. Because buoyancy tends to float bubbles away from dependent areas, bubble velocity would be expected to decrease as the vessel angle increased. We found that larger bubbles increased in velocity in the same direction as the blood flow at 0-, 10-, and 30 degree vessel angles and decreased when the vessel was positioned at 90 degrees. Smaller bubbles did not change velocity from 0 to 30 degrees and increased in velocity in the same direction as blood flow at 90 degrees. In 10 anesthetized dogs, we studied the effects of 0-, 10-, 15-, and 30-degree Trendelenburg's position on carotid artery distribution of gas bubbles injected into the left ventricle or ascending aorta. Regardless of the degree of the Trendelenburg position, the bubbles passed into the carotid artery simultaneously with passage into the abdominal aorta. We conclude that the forces of buoyancy do not overcome the force of arterial blood flow and that the Trendelenburg position does not prevent arterial bubbles from reaching the brain. PMID- 3341825 TI - Loss of the somatosensory evoked response as an indicator of reversible cerebral ischemia during hypothermic, low-flow cardiopulmonary bypass. AB - We assessed somatosensory evoked response (SSER) as a monitor of cerebral protection during nonpulsatile, hypothermic cardiopulmonary bypass (CPB). In 13 dogs under CPB, extracorporeal flow rate (EFR) thresholds for loss of SSER were determined by stepwise reduction of the EFR from 2.0 to 0.25 L/min/m2 at perfusion temperatures of 35 degrees C, 30 degrees C, 25 degrees C, and 20 degrees C. Testing began at 35 degrees C in Group 1 (N = 6) and at 20 degrees C in Group 2 (N = 7). Immediately on loss of SSER (denoted as a decrease of 80% or more in the amplitude of the somatosensory evoked potentials), EFR was restored to 2.0 L/min/m. Thresholds for loss of SSER ranged between 0.75 and 0.25 L/min/m2. SSER was always restored on return of EFR to 2.0 L/min/m2; thus loss of SSER was a reversible ischemic change. Both groups had similar threshold values at 35 degrees C, but at lower temperatures, Group 1 thresholds were significantly higher than those in Group 2. Since 35 degrees C was the first test temperature for Group 1 but the last for Group 2, EFR reduction at 35 degrees C apparently caused neurophysiological changes (depletion of cortical energy reserves), which diminished subsequent tolerance to ischemia, but EFR reduction at 20 degrees C did not. Our findings show that loss of SSER warns of reversible cerebral ischemia, and support SSER monitoring as a useful measure of cerebral function during low-flow, hypothermic CPB. PMID- 3341826 TI - Extrinsic obstruction of the Medtronic-Hall disk valve in the mitral position. AB - Three cases of acute extrinsic obstruction of the Medtronic-Hall prosthesis in the mitral position are described. In 2 cases papillary muscle and in 1 case suture overhang caused sticking of the tilting disk against the valve rim. The mechanisms of extrinsic obstruction of the tilting disk valve, its recognition, and its prevention are discussed with a review of the literature. PMID- 3341827 TI - Combined radiological and surgical management of arteriovenous malformation of the lung. AB - Multiple, bilateral arteriovenous malformations (AVMs) of the lung are diagnostically and therapeutically challenging. In staged procedures over seven days, a 19-year-old woman underwent blocking of the feeding artery to six moderate-sized AVMs in the left lower lobe, embolization of three more AVMs in the left lower lobe, and resection of a large AVM in the right lower lobe through a right-sided thoracotomy. These procedures preserved maximal lung tissue, and one year later the patient is essentially symptom free. PMID- 3341828 TI - Massive thymic hyperplasia in an adolescent. AB - Massive thymic hyperplasia (weight, greater than 100 gm) is a rare lesion in adolescents, and most of the anterior mediastinal masses are true neoplasms. We present a case of massive thymic hyperplasia, in which a 680-gm thymus was resected from a 15-year-old boy. We also present the computed tomographic scan appearance of this lesion, which differed from that previously described, and correlate the histological and radiological findings. PMID- 3341829 TI - Endobronchial metastases from prostatic carcinoma. AB - Prostatic carcinoma presenting with pulmonary symptoms is unusual. We describe the case of a 59-year-old man whose disseminated prostate cancer was diagnosed with bronchoscopy. To our knowledge, this represents the second reported case of prostate cancer that manifested with endobronchial symptoms. The importance of this entity and clinical and therapeutic aspects are also discussed. PMID- 3341830 TI - Renal failure following cardiac surgery in a 2.8-kg infant managed with continuous arteriovenous hemofiltration. AB - Renal failure occurred after repair of transposition of the great vessels with ventricular septal defect in a 2.8-kg infant and was managed successfully with continuous arteriovenous hemofiltration. The infant lost the weight that had been gained as extravascular water, thereby simplifying her fluid, electrolyte, and nutritional management. She ultimately died of cardiac failure. PMID- 3341831 TI - Method for removal of the St. Jude valve. AB - A method is presented for removal of the St. Jude Medical valve when it must be replaced with another prosthesis. The sewing ring is transected in the radial direction, freeing the rigid portion of the valve. This is then removed, allowing the remainder of the sewing ring to be excised under direct vision. This method simplifies and increases the safety of this procedure. PMID- 3341832 TI - Dynamic left ventricular outflow tract obstruction when the anterior leaflet is retained at prosthetic mitral valve replacement. PMID- 3341833 TI - Hypothermic phrenic nerve injury. PMID- 3341834 TI - The indigestible curriculum. PMID- 3341835 TI - Role of the laboratory in treatment of the poisoned patient. PMID- 3341836 TI - High-dose furosemide in the treatment of refractory congestive heart failure. AB - Thirty-five patients with severe chronic congestive heart failure that was refractory to conventional therapy were given high dosages of furosemide (250 to 4000 mg/d) because of significantly reduced renal function (mean endogenous creatinine clearance, 0.53 mL/s/1.73 m2 [32 mL/min/1.73 m2]). Natriuresis, weight reduction (mean, 11 kg), and relief of symptoms were achieved in all patients. The mean survival after the start of the high-dose furosemide therapy was 11.3 months (range, 0.5 to 36 months) (n = 35). When this therapy eventually failed, long-term intermittent hemofiltration was performed in eight selected cases, further prolonging survival (mean, 3.0 months). High-dose furosemide therapy and hemofiltration improved the quality of life and prolonged survival. The use of diuretics in congestive heart failure should therefore include treatment with high-dose furosemide, which is effective and can be given over a long period without serious side effects. PMID- 3341837 TI - Magnesium deficiency in patients with ischemic heart disease with and without acute myocardial infarction uncovered by an intravenous loading test. AB - An intravenous magnesium-loading test with 30 mmol/L of magnesium was used to evaluate the magnesium status in 38 patients with ischemic heart disease (IHD) admitted to the coronary care unit with suspected acute myocardial infarction (AMI), in ten healthy volunteers (control group), and in nine patients with chronic IHD in a stable phase of their disease (chronic IHD group). Sixteen of the patients admitted with acute disease proved to have AMI (AMI group) and 22 did not (non-AMI group). Patients with IHD both with and without AMI retained significantly more magnesium (9.3 and 10.7 mmol/L [22.6 and 26 mg/dL], respectively) than did the control group (1.4 mmol/L [3.4 mg/dL]). This 34% magnesium retention points to a state of magnesium deficiency in patients with IHD. However, since the patients with and without AMI did not differ, the observations do not indicate that AMI is associated with a more severe magnesium deficiency than that found in other IHD patients without AMI. When the patients with IHD were subgrouped according to long-term diuretic treatment, the patients (n = 19) receiving long-term diuretic treatment had a 39% retention of magnesium (11.6 mmol/L [28.2 mg/dL]) compared with a 29% retention (8.7 mmol/L [21.1 mg/dL]) observed in 19 patients who were not receiving long-term diuretic treatment. This observation was not influenced by the presence or absence of AMI. An even higher level of magnesium retention (17.1 mmol/L [41.6 mg/dL] equals 57% retention) was found when investigating patients with chronic ischemic heart disease in a stable phase of their disease. This indicates that patients with IHD may be severely magnesium deficient; that long-term diuretic treatment contributes to this deficiency, but that diuretic treatment per se is not the only cause of this condition. PMID- 3341838 TI - Changing concepts in surgical management of renovascular hypertension. AB - As newer surgical techniques and concepts have emerged, including revascularization of the totally occluded renal artery and alternatives to aortorenal bypass (hepatic, splenic, or iliac artery to renal artery grafts), our patient population has changed. Patients with diffuse atherosclerotic disease, bilateral renal artery stenosis, totally occluded renal arteries, and azotemia are being referred for renal revascularization, thereby changing the indications for operation and the results that can be anticipated. Although our results in patients operated on solely for uncontrollable hypertension or renal failure have been successful, much work needs to be done to improve the results obtained when patients have a combination of uncontrollable hypertension and renal failure. PMID- 3341839 TI - Gynecomastia associated with calcium channel blocker therapy. AB - Gynecomastia is a reaction that is not usually associated with calcium channel blocker therapy. The Division of Epidemiology and Surveillance, within the US Food and Drug Administration (Rockville, Md), has received 31 reports of gynecomastia occurring after the use of these drugs. The underlying mechanism of this reaction is unknown, although two patients did report elevated prolactin levels. Gynecomastia developed in two patients, resulting in the surgical removal of the breast and/or nodules before discontinuation of drug therapy. The possibility of an association between calcium channel blockers and gynecomastia should be considered before an extensive workup or surgical procedure is undertaken. PMID- 3341840 TI - Implications of discordance between clinical impression and toxicology analysis in drug overdose. AB - Two hundred nine cases of intentional drug overdose were reviewed to determine the importance of discordance between drugs identified by toxicology analysis and those suspected clinically. The laboratory agreed exactly with the clinical impression in 47% of cases. Clinically unsuspected drugs were identified by the laboratory in 27% of cases; the characteristics of these patients did not differ significantly from those of other patients. Unexpected toxicology findings led to changes in therapy in only three cases, and none of these changes appeared to have a major impact on outcome. Although routine comprehensive toxicology screening frequently may identify unsuspected drugs, it is likely that a policy of more selective use of the laboratory would not compromise the care of patients with drug overdose. PMID- 3341841 TI - The costs of employee smoking. A computer simulation of hospital nurses. AB - A computer simulation model of the economic impact of employee smoking on an employer was developed with a population of hospital nurses as the example. Net economic impact was calculated by estimating cumulative costs borne by the employer under various scenarios and comparing them with projected costs estimated from baseline data. The model included the following: baseline number of staff, baseline percentage of smokers, annual employee turnover rate, number of smokers interested in quitting, the cost of a smoking cessation program, expected success rate of a voluntary cessation program, smokers quitting spontaneously without a program, and employer-borne costs related to employee smoking. A variety of scenarios were constructed to generate a range of employer net economic impact figures and resulting percentages of smoking employees. Results showed that the benefits of a cessation program would be eliminated over several years, unless the prevalence of smoking in incoming employees was reduced. The most favorable scenario, combining a hospital cessation program and reduced smoking among new employees, generated cumulative savings, discounted at 5%, of $358,000 to $684,000 over an eight-year period. PMID- 3341842 TI - Diabetic neuropathy simulating conus medullaris syndrome. AB - Two diabetic patients presented with fecal incontinence, poor rectal sphincter tone, perianal hypoesthesia, and absent Achilles reflexes. These signs suggested the conus medullaris syndrome; however, no mass lesion was found to account for the clinical features. Fecal incontinence can occur in long-standing, insulin dependent diabetics. Back pain and absence of autonomic and peripheral neuropathy should indicate an etiology other than diabetic neuropathy. PMID- 3341843 TI - Pulmonary artery pseudoaneurysm. A potential complication of pulmonary artery catheterization. AB - A 70-year-old woman with pulmonary hypertension due to severe chronic obstructive pulmonary disease and long-standing mitral stenosis developed hemoptysis and a right upper lobe infiltrate during manipulation of a balloon-tipped flow-directed pulmonary artery catheter. Hemoptysis resolved spontaneously over several minutes, and the right upper lobe infiltrate cleared over several weeks, during which time a new right upper lobe nodule became apparent. Angiography disclosed the presence of a late-filling well-circumscribed saccular pseudoaneurysm. This was obliterated with an acute infiltrate with or without hemoptysis in the area subtended by a flow-director pulmonary artery catheter, and particularly when it is associated with manipulation of that catheter, the differential diagnosis should include pulmonary artery perforation as well as infarction. If the patient survives the episode, the possibility that a pseudoaneurysm has formed must be actively entertained and aggressively evaluated, since pseudoaneurysm is a potentially fatal lesion that is treatable. PMID- 3341844 TI - Frequency of isolated proximal colonic polyps among patients referred for colonoscopy. AB - The American Cancer Society now advocates screening asymptomatic populations over the age of 40 to 50 years for colonic malignancy. It is possible, however, that fecal occult blood testing and sigmoidoscopy to 60 cm would fail to identify patients with adenomatous polyps located only in the proximal colon. The purpose of this study was to determine how many patients without polyps in the distal 60 cm of the colon would have more proximal lesions. Ninety-eight consecutive patients with positive fecal blood test results or suspicious barium enema results were studied, using the assumption that if they had been seen six months earlier, when asymptomatic, they would have been candidates for screening examination. Forty-one (42%) of 98 patients had adenomatous polyps or cancer, and 15 (37%) of these patients had isolated proximal lesions. The polyp detection rate from 0 to 60 cm was significantly less than the detection rate for a full colonoscopy (27% vs 42%). We conclude that isolated proximal colonic polyps may be common. PMID- 3341845 TI - Hypomagnesemia in diuretic-treated patients. PMID- 3341846 TI - Hypercalcemia. PMID- 3341847 TI - Humanities in the medical school curriculum. PMID- 3341848 TI - Cancer and deep venous thrombosis. PMID- 3341849 TI - Painless mammography. PMID- 3341850 TI - Are the days of the sphygmomanometer past? PMID- 3341851 TI - Clinical utility of impedance plethysmography in the diagnosis of recurrent deep vein thrombosis. PMID- 3341852 TI - Is mammography painful? A multicenter patient survey. AB - Anecdotal reports of pain experienced during mammography have been a source of anxiety and concern for some women considering screening. To determine what asymptomatic women actually experience during mammography, a survey of 1847 women was performed at seven breast-imaging centers. Women recorded their experience on a six-point scale ranging from no discomfort to severe pain. Eighty-eight percent of the women experienced no discomfort (49%) or mild discomfort (39%). Only 9% experienced moderate discomfort; 1%, severe discomfort; and 1%, moderate pain. No woman had pain so severe that it would make her reconsider having a mammogram again. The degree of discomfort was slightly greater in women who complained of breast tenderness within three days prior to the mammogram but was not strongly related to age, menstrual status, or week of the menstrual cycle. We conclude that in a vast majority of women mammography causes no or mild physical discomfort and that actual pain is an uncommon occurrence. PMID- 3341853 TI - Continuity of care in hypertension. An important correlate of blood pressure control among aware hypertensives. AB - Hypertensive patients frequently discontinue follow-up care. In a population based survey of 4688 adults, we examined the impact of nonattendance on blood pressure control in aware hypertensives. Nonattendance was defined as a failure to visit a physician for hypertensive care within a six-month interval and was reported by 29% of 907 aware hypertensives. Nonattenders had a higher prevalence of diastolic blood pressure above 90 mm Hg (67% vs 30% for attenders). The nonattender profile was male, young, active in the work force, and without coexisting chronic diseases. Poor blood pressure control among nonattenders was associated with a lower treatment rate. Uncontrolled diastolic hypertension and less adherence to medications in nonattenders warrants concern by clinicians. PMID- 3341854 TI - The factors associated with fascicular block in acute anteroseptal infarction. AB - To elucidate the genesis and effect of fascicular block, 131 patients with acute Q-wave anteroseptal infarction were studied. Thirty-seven patients had new onset of fascicular block in the coronary care unit. The hospital mortality rate was 16%. Multivariate analysis was performed to determine the important variables related to the occurrence of fascicular block and hospital mortality based on 17 clinical variables obtained at the time of hospital admission. Serum potassium level and heart rate were the significant factors predicting the occurrence of fascicular block, whereas cardiac output and arterial oxygen tension were important for hospital mortality. Therefore, not only the rise in the heart rate but also the effect of the serum potassium level on the conduction system are independent factors related to the occurrence of fascicular block, and fascicular block in itself has no significant influence on the hospital mortality. PMID- 3341855 TI - Sex-related severity of inflammation in parenchymal brain cysticercosis. AB - To determine sex-related differences in the severity of host inflammatory reaction to cysticercosis, we studied computed tomographic findings in 100 patients with parenchymal neurocysticercosis and cerebrospinal fluid results in 239 patients with subarachnoid neurocysticercosis. Computed tomographic and cerebrospinal fluid data in male subjects were compared with those obtained in female subjects. We found that when cysticerci are found in brain parenchyma, women develop a greater degree of inflammation; such differences disappear when cysticerci are found in the subarachnoid space. Our results point out the possibility of a factor located within brain parenchyma that accounts for the observed sex-related differences in the severity of immune response to the parasite; this factor could also play a role in the pathogenesis of other immunologically mediated diseases of the brain that may occur more frequently in women. To our knowledge, this study is the first in demonstrating that sex is a risk factor for the severity of inflammatory response within brain parenchyma to a parasitic disease. PMID- 3341856 TI - Epidemiology of acute respiratory illness during an influenza outbreak in a nursing home. A prospective study. AB - We observed an influenza epidemic caused by influenza A/Arizona/82 (H3N2) in a nursing home during 1982 to 1983. A survey indicated that 59% of the residents were immunized before the outbreak. The outbreak was observed to begin in November, peak in February, and disappear in April. A significant level of herd immunity may have accounted for the slow progression through the nursing home. In addition, serologic evidence of concurrent infection with respiratory syncytial virus, parainfluenza virus, and Mycoplasma pneumoniae was present in many residents. Epidemics of influenza in a closed, partially immunized population in a nursing home may proceed at a slower rate than in an open, largely unimmunized community. By monitoring for infection with other respiratory agents, the complex nature of the outbreak in this nursing home became evident. PMID- 3341857 TI - Association of influenza immunization with reduction in mortality in an elderly population. A prospective study. AB - We prospectively studied the efficacy of influenza vaccine during an influenza A/Arizona/80 (H3N2) outbreak at the Jewish Home and Hospital for the Aged in New York in the winter season of 1982 to 1983. All patients had been offered influenza vaccine before the outbreak; 181 chose to be vaccinated and 124 refused vaccination but agreed to participate in the study. Among those with serologic evidence of influenza infection, respiratory illness was significantly more common in the unvaccinated group (six of 14 vs one of 22). The overall mortality was 13 (7.2%) of 181 in the vaccinated group and 22 (17.7%) of 124 in the control group. The vaccinated and the control groups were examined for comparability. A logistic regression analysis, which controlled for differences in sex and level of nursing care, indicated that the difference in mortality was still significant, with a summary odds ratio of 2.7. The relative risk of death in the unvaccinated group was comparable at 2.18. Influenza vaccine reduced the mortality by 59% in the vaccinated group compared with the control group. PMID- 3341858 TI - High rate of methicillin resistance of Staphylococcus aureus isolated from hospitalized nursing home patients. AB - Three series of studies were conducted between 1984 and 1986 at two community hospitals in Chicago to determine the frequency of methicillin resistance of Staphylococcus aureus isolated from hospitalized nursing home patients. Overall, 76 (49%) of 155 patients with S aureus clinical isolates admitted from 25 nursing homes had methicillin-resistant S aureus. In 1986, 53.1% of patients with S aureus infection or colonization among nursing home patients had the resistant strain, in contrast with 13.2% among patients from the community. A high incidence of methicillin-resistant S aureus infection or colonization is a clinical feature of nursing home patients. This observation may lead to an improvement in the clinical management of the patients suspected of having S aureus infection and alterations in the current policy of nursing homes that bar admission of patients carrying the resistant bacteria. PMID- 3341859 TI - Food-borne botulism. A review of 13 outbreaks. AB - Thirteen outbreaks of food-borne botulism occurred between 1970 and 1984. Fifty patients were affected, with 30 of them requiring hospitalization. The number of patients per outbreak ranged from one to ten (mean, 3.8). All outbreaks were caused by home-prepared foods: nine by smoked ham, one by bacon, one by sausage, and one by mussels; contaminated food was not found in one outbreak. Bacteriologic study was performed in 11 outbreaks and type B toxin, the only found, was detected in eight of them. Generalized muscular weakness, visual disturbances, extreme dry mouth, and severe constipation were observed in all inpatients. Palpebral ptosis, dysphonia, urinary retention, postural hypotension, and respiratory impairment were also reported, but not in all inpatients. Identical, but less severe, manifestations were registered in the 20 ambulatory patients. Electromyographic study showed decreased motor action potential and posttetanic facilitation. Pulmonary function, studied in four inpatients, was decreased in three. All patients recovered fully. Management consisted of supportive measures, symptomatic treatment, and nursing care. Equine antitoxin was not administered and assisted ventilation was unnecessary. PMID- 3341860 TI - Pericardial effusion and left ventricular dysfunction associated with ascites secondary to hepatic cirrhosis. AB - Fluid retention in decompensated hepatic cirrhosis is frequently accompanied by edema, ascites, and hydrothorax. Whether pericardial effusion occurs in such patients has not been studied. Twenty-seven consecutively hospitalized patients with ascites secondary to alcoholic cirrhosis of the liver were studied, and 28 control subjects were studied with the use of an echocardiographic method to detect pericardial effusion and to evaluate their left ventricular (LV) function. Seventeen patients (63%) and three control subjects (11%) showed pericardial effusion. The prevalence of pericardial effusion in the patients was significantly greater than in the control subjects (chi 2 = 10.6). Although the mean values of the echocardiographic measurements of LV function of the patients and the control subjects did not differ significantly, the individual values of the patients varied considerably. Among the patients, six patients (27%) had LV dysfunction, 14 patients (64%) had normal values, and two patients (9%) had values suggestive of hypercontractility of the left ventricle. Furthermore, abnormal systolic motions of the mitral valve and/or septum were noted in eight patients (30%) but in none of the control subjects. Six patients with pericardial effusion on initial examination were evaluated after the resolution of their ascites; pericardial effusion disappeared in two patients, diminished in two others, and remained unchanged in two patients. Resolution of ascites was also associated with normalization of the systolic motion of the mitral valve and septum. It was concluded that pericardial effusion is common in patients with ascites secondary to alcoholic hepatic cirrhosis and that its presence is probably related to fluid retention. PMID- 3341861 TI - Pregnancy and paroxysmal nocturnal hemoglobinuria. AB - Our study concerns eight pregnancies, six of which were successful, in four patients with paroxysmal nocturnal hemoglobinuria (PNH). Several complications of PNH during pregnancy were prevented: chronic anemia, folate and iron deficiency, and deep-vein thrombosis. During puerperium, acute hemolytic crises, most probably triggered by delivery, were observed in two patients. Thrombotic complications could be prevented by early initiation of an anticoagulant therapy after delivery. The only neonatal complication, observed in two cases, was isoimmune hemolytic anemia related to the multiple blood transfusions received before and during pregnancy. These results show that successful pregnancies are possible in women with PNH provided that both the obstetricians and physicians in charge monitor the pregnancies closely. PMID- 3341862 TI - Q fever. A call to heighten our index of suspicion. AB - The prevalence of Q fever infection is probably underestimated. In Michigan, the first two reported human cases of Q fever occurred in 1984. The case-patients lived in adjacent, rural counties and had multiple exposures to goats. We conducted a serosurvey of goat owners and a reference population to compare the prevalence of Q fever antibodies in the two-county area. Goat owners were almost three times more likely to be seropositive with Q fever antibodies than the reference population (43% vs 15%). Among goat owners, individual and household seropositivity prevalences were positively correlated with the number of goats, the number of positive goats, and the number of goat births on the farm. Q fever should be considered more often in the differential diagnosis of patients with compatible illness, especially those with frequent animal contact. PMID- 3341864 TI - Graves' disease. Influence of age on clinical findings. AB - To determine the influence of age on the signs and symptoms of hyperthyroidism we prospectively examined 880 patients and matched them by age, sex, race, and visit date with similarly examined euthyroid control subjects. Many signs and symptoms showed little change with age until after the fifth decade of life when they began to decrease gradually. Findings that increased with age were weight loss and atrial fibrillation, while those that decreased most markedly with age were increased appetite and weight gain. The diagnosis is more difficult as age progresses because there are fewer findings and because the significance of those present may not be appreciated. Identification of the most sensitive and specific signs and symptoms in each age decade should improve the early detection of hyperthyroidism. PMID- 3341863 TI - Human immunodeficiency virus infection in hemodialysis patients. Baltimore-Boston Collaborative Study Group. AB - Patients undergoing chronic hemodialysis receive multiple blood transfusions and, thus, are susceptible to infections transmitted through blood and blood products, including infection with human immunodeficiency virus (HIV). To determine the prevalence of antibody to HIV among patients undergoing chronic hemodialysis in Baltimore and Boston in 1985, we conducted a cross-sectional seroprevalence study. Repeatedly enzyme-linked immunosorbent assay (ELISA)-positive serum samples were tested by Western blot analysis. Among 435 patients in Baltimore, 12 (2.8%) were seropositive by both ELISA and Western blot techniques. Among 90 patients in Boston, three (3.3%) were seropositive. Among 100 frozen serum samples obtained from another Boston hemodialysis population in 1980, only one was seropositive. Many repeatedly ELISA-positive specimens were observed in each of the three groups studied, especially the serum samples that had been stored at -30 degrees C to -70 degrees C for four years. Most were nonspecifically reactive as demonstrated by reactivity with an H9-control ELISA plate. Patients undergoing hemodialysis, many of whom have received frequent transfusions in the past, are at increased risk for prior infection with HIV. Serologic testing for either screening or case-finding purposes must be conducted with great attention to specificity; serum samples frozen for prolonged periods are especially likely to be nonspecifically ELISA positive. These findings have implications concerning case-finding purposes, dialysis procedures, renal transplantation, and seroepidemiologic research. PMID- 3341865 TI - Strongyloidiasis in an institution for mentally retarded adults. AB - A serologic and epidemiologic survey was undertaken to explain the high incidence of eosinophilia (14.1%) in nine of 64 residents of a facility for mentally retarded adults in Pennsylvania. Seven residents had antibodies to Strongyloides stercoralis as determined by an IgG enzyme-linked immunosorbent assay system (10.9%) and five (71.4%) of this subset had persistent eosinophilia, suggesting a strong association. Sex, race, age, ward, degree of retardation, and medication were not associated with eosinophilia. Stool examination revealed S stercoralis larvae in two residents with S stercoralis antibodies and eosinophilia. Follow-up studies after thiabendazole treatment of the residents with S stercoralis antibodies showed resolution of eosinophilia and disappearance of S stercoralis antibodies in most. Eosinophilia in an adult institutional setting may be associated with strongyloidiasis, even in a nonendemic area. The enzyme-linked immunosorbent assay for antibody to S stercoralis may be useful in diagnosing or monitoring therapy of strongyloidiasis. PMID- 3341866 TI - Ringed sideroblasts in primary myelodysplasia. Leukemic propensity and prognostic factors. AB - Among 123 patients with ringed sideroblasts on bone marrow aspirates, 85 had acquired ringed sideroblasts with primary myelodysplasia. The patients were placed in categories modified from the French-American-British classification based on percentages of ringed sideroblasts and myeloblasts in the initial bone marrow. Overall, 48% (41/85) of patients with myelodysplasia developed acute leukemia. Primary acquired sideroblastic anemia was the most favorable category with longer survival and 13.8% (4/29) leukemic conversions. Variables correlating with leukemic transformation included male sex, thrombocytopenia, neutropenia, and pseudo-Pelger-Huet neutrophils. Only two variables had independent predictive value by multivariate regression analysis: a high percentage of myeloblasts and a low percentage of ringed sideroblasts. Numerous ringed sideroblasts strongly predicts a more favorable course in myelodysplastic patients. PMID- 3341867 TI - Endomyocardial biopsy in 30 patients with primary amyloidosis and suspected cardiac involvement. AB - Thirty patients with primary amyloidosis in whom cardiac involvement was suspected underwent endomyocardial biopsies. Medical records and biopsies were reviewed and echocardiograms were interpreted by observers who were unaware of the recorded findings. Cardiac amyloidosis was documented by endomyocardial biopsy in 30 (100%) of the patients. In two patients, amyloid was present in only one of four specimens, suggesting that a minimum of four biopsy samples is necessary to eliminate the possibility of sampling error. Only 36 (55%) of 65 biopsy specimens of extracardiac tissues contained amyloid. Findings were positive for amyloidosis in 11 (58%) of 19 rectal biopsies and in 16 (52%) of 31 bone marrow biopsies. Of interest, only the endomyocardial biopsy tissues were positive for amyloid in eight (27%) of the 30 patients, among whom 12 extracardiac biopsies had been performed. Two-dimensional echocardiography was consistent with the diagnosis of amyloidosis in 19 (68%) of 28 patients and was abnormal but nonspecific in the remainder. Endomyocardial biopsy frequently provides information about cardiac involvement with amyloid when biopsy of other organs is negative or echocardiography is nonspecific. PMID- 3341868 TI - Screening for pseudohypertension. A quantitative, noninvasive approach. AB - We studied 36 hypertensive men, aged 60 years or older, and compared direct intra arterial diastolic blood pressure (BP) measurements, indirect cuff mercury sphygmomanometer measurements, and automatic infrasonic recorder (IR) measurements. We used a receiver operating characteristic curve to determine whether a difference between the cuff and IR diastolic BP could identify patients likely to have pseudo-hypertension (cuff-intra-arterial diastolic BP difference of 10 mm Hg or greater). We found that a cuff-IR difference of 4 mm Hg could identify the majority of patients with pseudo-hypertension (sensitivity, 93%; specificity, 64%; positive predictive value, 62%; negative predictive value, 93%). We concluded that the IR is an accurate, quantitative, noninvasive substitute for intra-arterial measurements and may be the preferred technique for screening and monitoring of blood pressure in elderly hypertensive patients. PMID- 3341869 TI - Utility of impedance plethysmography in the diagnosis of recurrent deep-vein thrombosis. AB - Serial impedance plethysmography has been shown to be a safe and effective alternative to venography in the management of patients with clinically suspected acute venous thrombosis. The rate of normalization of an initial abnormal impedance plethysmogram and, consequently, the usefulness of impedance plethysmography in the management of patients with recurrent symptoms is, however, unknown. In a prospective cohort follow-up study, 161 consecutive patients with proved venous thrombosis and abnormal impedance plethysmograms were studied for one year. After 3, 6, 9, and 12 months, the impedance plethysmograms had normalized in 67%, 85%, 92%, and 95% of the patients, respectively. Thirty five patients (22%) returned with clinically suspected recurrent thrombosis, of whom 31 had normal impedance plethysmograms prior to their return. In 18 of these patients, repeated tests were normal; these patients did not undergo anticoagulant therapy, and follow-up disclosed no subsequent adverse consequences. In the other 13 patients, the test again became abnormal; 11 patients were shown by venograms to have recurrent deep-vein thrombosis. Consequently, 29 (83%) of the 35 patients in whom the suspicion of recurrent thrombosis arose could have been managed with impedance plethysmography alone without the necessity for venography or anticoagulant therapy. It is concluded that normalization of impedance plethysmography tests occurs in almost all patients within nine months, and that serial impedance plethysmography is useful for patient management in nearly 90% of patients presenting with recurrent symptoms. PMID- 3341870 TI - Pulmonary hypertension from prominent vascular involvement in diffuse amyloidosis. AB - Pulmonary arterial hypertension was found in a patient with myeloma who had a diffuse lung lesion. Echocardiographic and hemodynamic data from pulmonary arterial catheterization demonstrated relatively well-preserved left ventricular function. The diagnosis of diffuse pulmonary amyloidosis was established by open lung biopsy, which revealed severe diffuse vascular deposition of amyloid with mild involvement of the alveolar septa. Pulmonary arterial hypertension secondary to vascular deposition of amyloid in the lungs is rare. This case corroborates the clinicopathologic relationship. PMID- 3341872 TI - Hyperprolactinemia, infertility, and hypothyroidism. A case report and literature review. AB - A 30-year-old woman presented with infertility, hyperprolactinemia, and pituitary enlargement. Although relatively asymptomatic, she was found to have primary hypothyroidism. She became pregnant within a month following institution of levothyroxine replacement, and the pituitary enlargement resolved within one year. We discuss the relationship between hypothyroidism, hyperprolactinemia, and pituitary enlargement. This case emphasizes the need for thyroidal status evaluation in patients with presumptive prolactin-producing pituitary tumors before initiation of therapy for the hyperprolactinemia. PMID- 3341871 TI - Thyrotoxic periodic paralysis in a hispanic man. AB - Thyrotoxic periodic paralysis occurs much more frequently in Orientals than in whites, and has rarely been reported in patients of Hispanic descent. A 28-year old Mexican man presented with acute onset of bilateral lower extremity weakness after ingestion of a large carbohydrate meal. Laboratory investigation revealed severe hypokalemia, with a serum potassium level of 2.1 mmol/L (2.1 mEq/L), and hyperthyroidism. Administration of potassium chloride resulted in normalization of the serum potassium level and resolution of muscle weakness. Treatment with propranolol, and subsequent restoration of a euthyroid state with iodine 131, was effective in preventing further episodes of paralysis. Thyrotoxic periodic paralysis, although rare, may occur in Hispanic patients, and should be considered in the differential diagnosis of muscle weakness in this population. PMID- 3341874 TI - Use of cholestyramine in the treatment of digoxin intoxication. AB - The bile acid-binding resin cholestyramine was administered in a dose of 4 g every six hours to a patient with digoxin intoxication. The serum digoxin concentration declined rapidly, and the digoxin half-life decreased from 75.5 hours to 19.9 hours while cholestyramine was administered. All signs and symptoms of toxic reaction subsided during the period of cholestyramine therapy, which correlated with the decline in digoxin concentrations. Cholestyramine and a related agent, colestipol, presumably interrupt the enterohepatic recycling of digoxin to enhance elimination. These agents represent potentially useful adjunctive measures in the management of non-life-threatening digitalis intoxication. PMID- 3341873 TI - Risk factors for severe bradycardia during oral clonidine therapy for hypertension. AB - We identified eight hypertensive patients who developed severe bradycardia during oral clonidine hydrochloride therapy. Seven patients had sinus bradycardia, four had long sinus pauses, two had junctional bradycardia, and two had high-degree atrioventricular block. Three populations at risk for severe bradycardia during oral clonidine therapy were identified: patients with renal insufficiency, patients with clinical sinus node dysfunction, and patients who had developed bradycardia while taking other sympatholytic agents or who were currently receiving another sympatholytic drug. Clonidine effects were dissociated in two patients who were not hypotensive despite severe bradycardia. Asymptomatic patients required only dose reduction or discontinuation of clonidine therapy. Symptomatic patients responded inconsistently to intravenous atropine sulfate therapy; one responded to isoproterenol therapy, and one required temporary artificial pacing. Awareness of the variable presentation and response of this bradycardia to medical therapy will assist patient management. The incidence of this complication is low (less than 0.3%), but attention to risk factors should make clonidine-induced bradycardia even less frequent. PMID- 3341875 TI - Predisposing factors for the diabetic hyperosmolar state. PMID- 3341876 TI - Bacterial endocarditis following nail trauma. PMID- 3341877 TI - C5 deficiency and meningitis in a Swiss family. PMID- 3341879 TI - Comparison of patients with and without poststroke major depression matched for size and location of lesion. AB - Patients who developed major depression within two years following stroke (n = 13) were compared with patients who did not become depressed in the same period (n = 13) but who did have a similar size and location of lesion as in the depressed group. Although the depressed patients were not significantly different from the nondepressed patients in background characteristics, history of depressive disorder, neurological impairment, or social functioning, the depressed group had greater cognitive impairment as measured by Mini-Mental State score. In addition, the depressed group had significantly larger lateral and third ventricular to brain ratios than nondepressed patients on computed tomographic scan analysis. The results suggest that poststroke depression itself may produce an intellectual impairment; subcortical atrophy, which likely preceded the stroke lesion, may produce a vulnerability for depression following stroke. PMID- 3341878 TI - Family factors and the course of bipolar affective disorder. AB - Measures of family attitudes (expressed emotion [EE]) and interactional behaviors (affective style [AS]), both of which have been found to predict relapse in schizophrenia, were obtained from key relatives of 23 hospitalized recently manic bipolar patients. Patients were then followed up for a period of nine months after hospital discharge and rated on measures of clinical course, social adjustment, and medication compliance. Levels of intrafamilial EE and AS were found to predict likelihood of patient relapse at follow-up, especially when used as conjoint predictors of patient outcome status. Levels of AS also predicted degree of social adjustment at follow-up. The predictive relationships observed were independent of patient medication compliance, treatment regimen, baseline symptoms, demographics, and illness history. Results suggest that the emotional atmosphere of the family during the postdischarge period may be an important predictor of the clinical course of bipolar disorder. PMID- 3341880 TI - Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data. AB - Using electroencephalographic sleep data from a sample of 235 elderly subjects, discriminant function analyses of sleep alterations in depression and dementia were performed. Overall, 80% of patients were correctly classified using a backward discriminant function analysis, and 81% with a general stepwise discriminant function analysis. Four measures contributed to the separation of depressed and demented patients: rapid eye movement (REM) sleep latency (lower in depressives); REM sleep percent (higher in depressives); indeterminate non-REM sleep percent (higher in demented patients, reflecting greater loss of spindles and K complexes); and early morning awakening (more marked in depressives). When both discriminant functions were subjected to cross-validation in independent subsamples, both procedures correctly identified 78% of patients. The classification functions derived from nondemented depressed and nondepressed demented patients were applied to a mixed-symptom group (n = 42). Overall, 27 patients (64%) with either depressive pseudodementia or dementia with depressive features were correctly classified using the same four predictor variables. These findings suggest that sleep physiological alterations of depression and dementia reflect between-group differences in sleep continuity, sleep architecture, and REM sleep temporal distribution, and that the differences are statistically reliable, in both diagnostically pure and mixed clinical presentations. These findings are discussed in the context of current hypotheses of sleep regulation and its mechanisms. PMID- 3341881 TI - Electroencephalographic sleep in mania. AB - Electroencephalographic (EEG) sleep patterns were examined in nine unmedicated patients meeting DSM-III-R criteria for a current manic episode (four men and five women) for two to four consecutive nights. Compared with age- and sex matched normal control subjects, manic patients exhibited significantly decreased total recording period, decreased time spent asleep, increased time awake in the last two hours of recording, shortened rapid eye movement (REM) latency, increased REM activity, and increased REM density. These results suggest that mania is associated with marked disturbances of sleep continuity and REM measures. Sleep continuity and REM sleep abnormalities of a similar nature and degree have been reported in major depression and psychotic depression. Thus, it is possible that various forms of affective disorders and psychotic disorders have pathophysiologic mechanisms in common. PMID- 3341882 TI - Excess mortality among formerly hospitalized child psychiatric patients. AB - Mortality was investigated in 881 male and 450 female formerly hospitalized child psychiatric patients in a four- to 15-year follow-up. Death from natural causes was not increased, but death from unnatural causes occurred at a rate more than twice as high as expected based on age- and sex-matched comparisons with the general population of the state of Iowa. Increased risk of unnatural death was found in five of eight psychiatric diagnostic categories but was significant only for Mental Reasoning, a category that combined patients with organic mental disorders, schizophrenia, or mental retardation. Clinical variables associated with an excess rate of unnatural death included age 15 years or older at the time of admission, the absence of a second psychiatric diagnosis, the presence of previous psychiatric hospitalizations, and the presence of a seizure disorder. Among the 23 unnatural deaths, the 11 (47.8%) suicides were excessive, but accidents and homicides were not. PMID- 3341883 TI - Causes of death in DSM-III schizophrenics and other psychotics (atypical group). A comparison with the general population. AB - Causes of death were determined in a cohort of DSM-III schizophrenics and in a group of "other" psychotics (with schizoaffective disorder, schizophreniform disorder, and atypical psychoses), and comparisons were made with the general population. Five causes of death were considered in this analysis: (1) infections, (2) neoplasms, (3) cardiovascular, (4) unnatural, and (5) other. Suicide occurred in excess among other psychotics compared with schizophrenics and with the general population. PMID- 3341884 TI - The importance of past psychological trauma and pathophysiological process as determinants of current biologic abnormalities. PMID- 3341885 TI - Relative hypophosphatemia in patients with panic disorder. PMID- 3341886 TI - Metabolic and heart rate responses to submaximal arm lever and arm crank ergometry. AB - Previous studies have shown that arm cranks and arm levers, working as propulsion mechanisms for nonambulatory individuals, may have mechanical and physiologic advantages over standard handrim wheelchairs. This study evaluated physiologic responses to arm lever and arm crank ergometry using identical workloads. An arm lever ergometer (ALE) was constructed and adapted to an arm crank ergometer (ACE) so that equal workloads could be applied with both ergometers. Fifteen able bodied men and 15 able-bodied women exercised at a low (15 watts) and a high (45 watts) workload, with a three-minute rest interval. While exercising at each level, oxygen consumption (VO2), minute ventilation (VE), and heart rate (HR) were monitored. When low workloads with ALE and ACE were compared, no significant differences (p greater than 0.05) were demonstrated in any of the variables for men or women. For the men, at the high workload, the ALE elicited significantly lower (p less than 0.05) VO2 (by 9.8%), HR (by 6.3%), and VE (by 7.5%), than did the ACE. For the women, at the high workload, VO2 was significantly lower (p less than 0.05) (by 7.6%) with the ALE, as was VE (by 7.5%), but HR, although 3.3% lower with the ALE, was not significantly different (p greater than 0.05) from the ACE. These data suggest that the ALE is physiologically less stressful than the ACE at high workloads. Arm levers may, therefore, provide an advantage for handicapped persons when they propel themselves in wheelchairs. PMID- 3341887 TI - Recruitment and termination of electromyographic activity in the hemiparetic forearm. AB - Motor unit control measured by timed recruitment and termination of intramuscular electromyographic (EMG) activity provides muscle-specific quantification of deficits of the arm in chronic hemiparesis. Latencies to recruitment and termination of EMG activity of flexor carpi radialis and extensor carpi radialis longus were recorded from nine stroke patients and five age- and sex-matched control subjects, in response to buzzer signals, during maximal isometric wrist flexion and extension. Both agonist and antagonist recruitment times were slower in paretic than in control forearms (p less than .01). Termination of EMG activity occurred earlier in paretic forearms, primarily because of inability to maintain a prolonged muscular contraction. The effects of the variable lengths of testing trials reinforced these conclusions. The paretic extensor carpi radialis longus showed the greatest impairment with a very long latency to contract, and frequent failure to maintain a contraction. This study presents a new method of quantifying a common clinical problem in rehabilitation medicine. PMID- 3341889 TI - Ankle muscle activity during gait in children with cerebral palsy and equinovarus deformity. AB - Temporal electromyographic (EMG) characteristics of lower limb muscles during gait of spastic hemiplegic and diplegic children with cerebral palsy are described. All subjects were referred for presurgical evaluation of equinovarus deformity. The data indicated both similar and discriminating phasic EMG characteristics between groups of patients. All children displayed premature triceps surae activity beginning in swing phase of gait and continuing through stance. Tibialis posterior, normally active during stance, was also active during swing phase of gait. However, some patients displayed cocontraction of triceps surae and tibialis anterior during stance, together with hamstring muscle activity within normal limits. The remainder of the patients displayed a prolonged duration of hamstring activity. How this gait analysis contributed to presurgical decisions for equinovarus gait is discussed and compared with data from postsurgical gait analysis. PMID- 3341888 TI - Functional skills after spinal cord injury rehabilitation: three-year longitudinal follow-up. AB - Reports that spinal cord injury (SCI) patients maintain or improve functional abilities after initial rehabilitation have been limited by small sample size, inadequate functional measures, cross-sectional assessment at only one point in time, and lack of detailed statistical analysis. This study evaluated the follow up functional status levels of 236 patients with traumatic SCI who completed comprehensive inpatient rehabilitation and were also followed for three years. The sample population was 83% men, with a mean age of 27.0 years. The 100-point Modified Barthel Index (MBI) was used to assess functional abilities. The 75 patients with complete quadriplegia had mean MBI scores of 30.3 at rehabilitation discharge and 37.8 at three-year follow-up. The 53 patients with incomplete quadriplegia were discharged with a mean MBI score of 53.8, and scored 68.3 at three-year follow up. The mean MBI scores for the 66 patients with complete paraplegia were 72.0 at discharge and 75.6 at three-year follow-up. The 42 patients with incomplete paraplegia had mean MBI scores of 77.0 at discharge and 86.1 at three-year follow-up. Each of the four groups demonstrated stability or increases in the proportions of patients who were independent in performance of each of the 14 MBI component tasks from discharge to follow-up. The finding that SCI patients, in this large series, maintained or improved functional levels for three years after discharge is consistent with previous studies and is reassuring to rehabilitation providers. PMID- 3341890 TI - Exercise conditioning in the rehabilitation of patients with chronic obstructive pulmonary disease. AB - Fifty-nine patients with severe chronic obstructive pulmonary disease (COPD) performed pulmonary function and exercise tests before and after participation in a 12-day pulmonary rehabilitation inpatient program. Postdischarge follow-ups were performed at three months. Training consisted of twice daily aerobic exercise of 30 to 40 minutes' duration. Intensity of training was determined after exercise testing and approached the maximal limits of ventilation. In general, the program failed to demonstrate significant changes in pulmonary function. Exceptions were mid-expiratory flow rate (FEF25-75) (p less than .02) and peak flow rate (p less than .05). Evaluation of exercise capacity via maximal exercise testing yielded significant increases in caloric expenditure (p less than .001), peak exercise oxygen consumption (p less than .001), and work output (p less than .0001). Peak exercise ventilation increased significantly (p less than .005) due to an increase in tidal volume (p less than .002). Work efficiency improved with training, but the change was not statistically significant. Resting oxygen consumption and carbon dioxide production were decreased (p less than .05); tidal volume was increased (p less than .005). However, the significant increase noted in tidal volume did not alter minute ventilation. In general, the changes noted at 12 days were maintained at three months postdischarge. These data support the hypothesis that a short-term, in-hospital program of general exercise conditioning can improve work output, gas exchange, and mechanical efficiency without significantly affecting spirometric indices. These changes may translate into improved performance of activities of daily living and a sense of general well-being. PMID- 3341892 TI - Rigid removable dressing in a case of poor wound healing. AB - The rigid removable dressing technique for below-knee amputees has many advantages over other conventional systems. There is some reluctance to use this system in the presence of an open lesion. We present a patient with severe wound dehiscence who had success with this system. The advantages of the rigid removable dressing are protection of the stump and better shrinkage, combined with the ability to remove the dressing and look at the wound. This makes the technique ideal for a stump with poor wound healing. PMID- 3341891 TI - Exercise testing in patients with musculoskeletal handicaps. AB - To determine safe and effective exercise testing techniques for musculoskeletally handicapped individuals, 20 patients (mean age, 61 years) were studied. Types of handicaps included various degrees of paralysis of arms and legs, and leg amputations. Seventeen of the 20 patients had concurrent cardiovascular problems. All were currently hospitalized, engaged in various physical therapy exercises, and referred for exercise testing to increase rehabilitation therapy or for cardiovascular evaluation. Of 20 tests, arm ergometry was used in 15, leg or combination arm-leg ergometry in four, and treadmill in one. All patients completed testing with mean increases in heart rate (82 to 106 bpm arm, 88 to 125 other) and systolic blood pressure (114 to 127 mmHg arm, 118 to 146 other). Low grade atrial and ventricular ectopy occurred in eight patients, decrease or plateauing of systolic blood pressure in three, increased diastolic blood pressure in two, and significant (greater than or equal to 1mm) ECG S-T segment displacement in one. With the use of appropriate equipment for each patient, exercise testing can be done safely and effectively in musculoskeletally handicapped individuals. PMID- 3341894 TI - Reduction mammaplasty in adolescents with myelodysplasia. AB - Macromastia may occur in patients with myelodysplasia and paraplegia. Breast enlargement complicates weight shifts, crutch walking, sitting balance, and personal hygiene. Three patients with macromastia and myelodysplasia who underwent reduction mammaplasty are presented. Their postoperative recoveries were uncomplicated and each was symptomatically improved. PMID- 3341893 TI - Hypertension after brainstem stroke. AB - Paroxysmal hypertension associated with diaphoresis and facial flushing occurs after brain injury and after spinal cord lesion above the level of sympathetic outflow. This excessive sympathetic activity is due to the failure of inhibitory impulses from supraspinal vasomotor centers to reach the spinal sympathetic outflow. A case of brainstem stroke, with weakness in all four extremities, is presented. The patient experienced paroxysms of hypertension with bladder spasms, which subsided after treatment of the spasms resulting from bladder infection. Serum levels of dopamine, norepinephrine, and epinephrine were elevated during the episode and were normal after subsidence of the paroxysms. PMID- 3341895 TI - Acceptability of the NYU Number 1 Child-sized Body-powered Hand. New York University. AB - The NYU Number 1 Child-sized Body-powered Hand was field tested on 24 children with below-elbow limb deficiency. Identical in size (14.4cm, four-knuckle circumference) and shape to the Systemteknik myoelectric number 1 size hand, this hand offers a new prescription alternative for very young children with upper limb amputation. The participating children and prosthetic clinic teams reacted very favorably to the hand's appearance, function, and light weight. Maintenance reports during the three-month trial were primarily concerned with glove damage. Overall, the hand was received enthusiastically, and is now in commercial production. PMID- 3341896 TI - Toileting device for patients with decreased hand function. AB - Physical medicine and rehabilitation is involved with aiding patients in the performance of activities of daily living. The ability to independently perform the acts involved in personal hygiene is important to a disabled person's self esteem. This report describes a patient with weak distal upper limbs secondary to Guillain-Barre neuropathy, his difficulty with independent hygiene, and the device designed to aid independence in toileting. This device is easy and inexpensive to fabricate, and simple to use. It has applications beyond the Guillain-Barre population including patients with arthritis and burns and those with limited distal upper limb function. PMID- 3341897 TI - Pneumothorax and EMG. PMID- 3341898 TI - Soleus muscle atrophy in rats induced by cast immobilization: lack of effect by anabolic steroids. AB - To test the hypothesis that an anabolic steroid such as nandrolone decanoate (ND) will ameliorate or abolish disuse-mediated alterations resulting from five weeks of hindlimb immobilization, female Sprague-Dawley rats were divided into six groups: control, control + ND, shortened-immobilized, shortened-immobilized + ND, stretched-immobilized, and stretched-immobilized + ND. Immobilization was accomplished by wrapping hindlimbs with plaster of Paris. Nandrolone decanoate in sesame oil was administered via weekly intraperitoneal injection (7 mg/kg) while nontreated rats received equivalent volumes of the vehicle. After five weeks selected morphometric, biochemical, and mechanical parameters were examined in the slow-twitch soleus muscle (SOL). Muscle wet weight fell from a control value of 145 +/- 19 mg to 70 +/- 8 mg (p less than .05) in the immobilized-shortened group where ND had no effect (81 +/- 11 mg). Muscle stretch alone prevented weight loss (159 +/- 31 mg). The addition of ND resulted in significant SOL hypertrophy (200 +/- 42 mg), p less than .05. Immobilization resulted in a significant shift in muscle protein distribution toward sarcoplasmic protein, a change unaltered by ND but abolished by stretch. Muscle strength, as indicated by peak tetanic tension, fell 45% (p less than .05) as a result of shortened immobilization. Nandrolone decanoate had no effect on this condition, although the ameliorating effect of stretch was abolished when in combination with ND treatment. The elevation observed in maximal shortening velocity (shortened immobilized) was unaffected by ND alone, but abolished by stretch with or without ND treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3341899 TI - Prognostic endpoint yield of high-level versus low-level graded exercise testing. AB - The prognostic endpoint yield (PEY) of a low-level (less than or equal to 4.6 METS) vs a high-level graded exercise test administered soon after myocardial infarction was evaluated with 184 patients. Test endpoints considered prognostically significant for future cardiac events were (1) ST segment depression greater than or equal to 1mm, (2) angina pectoris, and (3) complex ventricular beats. Test endpoints were assigned to both low-level and high-level tests if they occurred less than or equal to 4.6 METS; test endpoints greater than 4.6 METS were assigned to the high-level test only. Allowing the 145 patients who were asymptomatic during the low-level test to continue into the high-level protocol revealed a 2.5 times greater occurrence of angina pectoris (38 vs 15), a 3.4 times greater occurrence of ST segment depression (27 vs 8), and twice the occurrences of ventricular beats (4 vs 2). This substantial increase in prognostic endpoint yield was demonstrated in the presence of a significantly longer exercise time with the high-level test (9.0 vs 5.1 min), with no significant difference between protocols for peak heart rate or systolic blood pressure. Therefore, a high-level graded exercise test appears to increase the yield of test endpoints with known prognostic importance. PMID- 3341900 TI - Fitness to drive a car after recovery from severe head injury. AB - Driving skills in relation to residual psychologic impairments were studied in a sample of patients who had survived severe head injuries several years earlier. Daytime driving was studied in an instrumented car that recorded lateral position control on a highway track and during rides in the subjects' own cars with a professional observer. In comparison with a control group matched by age and driving experience, the patients performed worse on both driving tasks. In addition, the patient group showed clear impairments on a neuropsychologic test battery, despite the long intervals since their injuries. However, the only relationships found between test performance and driving involved visuomotor ability and lateral position control. No relationship was found between neurologic status and driving skill. The results are discussed in terms of patients' compensatory potential. PMID- 3341902 TI - Papers read before the seventh annual meeting of the Surgical Infection Society, Philadelphia, May 11 to May 12, 1987--Part I. PMID- 3341901 TI - Tissue pressure management in the vocational setting. AB - A significant problem that confronts a spinal cord injured person who returns to work is how to design the work station and tasks so that pressure sores do not develop and compromise the worker's productivity. In this study, reach was investigated as a mechanism to cause weight shift during task execution. It is shown that by using an extended reach motion, it is possible to cause effective weight redistribution. By incorporating this type of motion in task design for mobility impaired workers, it should be possible to reduce their risk of developing pressure sores with a minimal effect on job performance. PMID- 3341903 TI - The microbiology of neonatal peritonitis. AB - To review the bacteriology of neonatal intra-abdominal sepsis, we reviewed peritoneal cultures from 86 newborns undergoing operation for necrotizing enterocolitis (NEC) for the type and incidence of microorganism recovered. As a control, we conducted a similar review in 59 children with perforated appendicitis during the same period. Necrotizing enterocolitis was characterized by a lower incidence of polymicrobial contamination (1.7 organisms per patient vs 2.4 organisms per patient, NEC vs appendicitis) and an uncharacteristic pattern of isolates. Although enteric gram-negative bacilli were recovered in 80% of newborns, the incidence of Escherichia coli was only 21% in the NEC group vs 69% in the appendicitis group, while Klebsiella and Enterobacter species represented the most common gram-negative isolates recovered (63% vs 17%). More than 50% of neonatal cultures yielded gram-positive cocci, most frequently coagulase-negative staphylococci (30% vs 0%) and enterococci (17% vs 5%), as compared with more frequent streptococcal isolates in the appendicitis group (50% vs 10%). Anaerobes were seldom recovered in NEC cases (6%), but they were present in 50% of appendicitis cases. Additionally, Candida isolates were recovered in 10% of NEC cases (0% of appendicitis group). These results indicate the unique bacteriology of peritonitis in the critically ill newborn and probably reflect abnormal colonization in the neonatal intensive care unit. PMID- 3341904 TI - Candida. A decreasing problem for the burned patient? AB - Multiple recent reports have suggested that Candida wound infection and sepsis are major complications of severe burn injury. Our current burn treatment plans include aggressive early burn excision and grafting, avoidance of invasive monitoring and central hyperalimentation lines, enteral nystatin, and judicious use of antibiotics. A retrospective review of 168 severely burned patients admitted to the Intensive Care Unit of the University of Washington Burn Center, Seattle, during the 18-month period from June 1984 through December 1985 was undertaken. Thirteen percent of these patients had one or more cultures positive for Candida from any site. Three patients (1.8%) developed Candida sepsis, which was diagnosed on the basis of clinical signs of sepsis, a positive blood culture for Candida, and at least two additional culture sites positive for Candida. All three patients were treated with amphotericin B. One of these patients died of Candida sepsis, for an overall mortality of 0.6%. Therefore, Candida septicemia was not a major cause of morbidity or mortality in our burn patients in the Intensive Care Unit during this 18-month period under the current management regimen. PMID- 3341906 TI - Soft-tissue infections caused by halophilic marine vibrios. AB - Marine Vibrio bacteria can cause illness and occasionally death to people who are exposed to seawater. These gram-negative bacteria can be found in ocean water and estuaries and in uncooked marine animals; they can cause primary sepsis, gastroenteritis, and soft-tissue infections. During a five-year period from 1981 to 1986, we encountered 51 patients with primary soft-tissue infections caused by marine vibrios. Thirty-nine patients developed cellulitis after direct exposure to ocean water, nine had eaten raw oysters, and three had no obvious exposure to seawater. Twenty-two patients (44%) had an underlying illness that might have made them compromised hosts and predisposed them to infection. Twelve patients developed necrotizing infections. Thirteen patients ultimately died. These infections are susceptible to many antibiotics. Debridement is necessary when tissue necrosis occurs. Surgeons should suspect a marine vibrio infection if cellulitis occurs in a patient who has been near ocean water or has eaten raw oysters. These infections may not become apparent until a traveler has returned home, a place that may be far from the ocean. PMID- 3341905 TI - Evidence that cathepsin B contributes to skeletal muscle protein breakdown during sepsis. AB - The mechanisms of accelerated skeletal muscle protein degradation during sepsis have not been fully elucidated. Activity of the lysosomal protease cathepsin B is increased in skeletal muscle during various catabolic states other than sepsis. In the present study the protein degradation rate and cathepsin B activity were determined in extensor digitorum longus and soleus muscles from nonseptic and septic rats. The protein degradation rate during incubation in vitro with or without the cathepsin B inhibitor leupeptin was also determined. Both protein degradation and cathepsin B activity were increased in muscles from septic rats. Incubation with leupeptin reduced, but did not normalize, the protein degradation rate in both extensor digitorum longus and soleus muscles from septic animals. These studies suggest that increased cathepsin B activity contributes to the accelerated muscle proteolysis seen during sepsis and that proteases other than cathepsin B are also involved. PMID- 3341907 TI - Hip disarticulation for paraplegics with decubitus ulcers. PMID- 3341908 TI - Localization and retrieval of bullets under surgical guidance. PMID- 3341910 TI - Hypothesis: sepsis, multiple systems organ failure, and the macrophage. PMID- 3341909 TI - False-negative angiograms in missed vascular injuries. PMID- 3341911 TI - The microbiology of multiple organ failure. The proximal gastrointestinal tract as an occult reservoir of pathogens. AB - The microbiology of infection acquired in the intensive care unit (ICU) was studied prospectively in 205 consecutive patients admitted to a surgical intensive care unit. A multiple organ failure (MOF) score was calculated for each admission. Susceptibility to ICU-acquired infection increased with increasing MOF scores. While Escherichia coli, Bacteroides fragilis, and enterococci were the most common isolates from infections present at the time of ICU admission, Staphylococcus epidermidis, Candida, and Pseudomonas dominated infections occurring in patients with high MOF scores. Mortality correlated highly with infection due to S epidermidis or Candida and only poorly with infection due to Pseudomonas or E coli; significant foci of invasive infection were frequently absent at autopsy. Quantitative cultures of proximal gastrointestinal fluid in 16 of these patients showed Candida, S epidermidis, and Pseudomonas to be the most common isolates, and all but one patient colonized with these organisms had invasive infection with the same organism. The proximal gastrointestinal tract appears to be an important occult reservoir of the predominant pathogens in MOF. PMID- 3341912 TI - Systemic complement activation produces hemodynamic changes characteristic of sepsis. AB - Zymosan was administered intravenously in graded doses to Sprague-Dawley rats to investigate the hemodynamic effects of systemic complement activation. At two hours, thermodilution cardiac output, mean arterial pressure, heart rate, systemic vascular resistance, hematocrit, effective hepatic and renal blood flows, and percent change in total hemolytic complement activity were measured on all animals. Progressively increasing doses of zymosan produced characteristic hemodynamic changes of progressively deteriorating stages of hyperdynamic sepsis. In addition, complement activation resulted in a redistribution of systemic blood flow with hepatic hypoperfusion similar to that seen in sepsis. Renal blood flow was unaffected early after complement activation. Additional rats were studied from the control and a representative zymosan-treated group at 24 and 48 hours to determine if the hemodynamic changes observed at two hours persisted or resolved. All systemic hemodynamic measures returned to normal at both 24 and 48 hours. Liver blood flow, however, remained depressed and actually deteriorated over time. Renal perfusion, which was stable at both two and 24 hours, fell below control values in the zymosan-treated group at 48 hours. We conclude that complement may be a mediator of both systemic and visceral flow abnormalities that precede, and perhaps precipitate, organ failure in trauma and sepsis. PMID- 3341913 TI - Direct effects of endotoxin on hepatocytes. Synthesis of a specific secretory protein. AB - The synthesis of acute-phase proteins by the liver during sepsis has been thought to be induced primarily by monokines released from activated macrophages, although glucocorticoid hormones may also stimulate this process to a lesser degree. According to this concept, synthesis of these proteins following administration of bacterial endotoxins would be an indirect effect and would not reflect a direct interaction of the endotoxin molecule with the hepatic parenchymal cell. We observed, however, that the synthesis of a 23-kilodalton protein was stimulated directly by the addition of lipopolysaccharide to cultures of primary mouse hepatocytes. The synthesis of this protein was also stimulated by glucocorticoids and interleukin 1. These findings demonstrate that certain hepatic proteins are subject to complex regulation by several factors thought to be important mediators of sepsis; in addition, they suggest that hepatic parenchymal cells may have the intrinsic capacity to respond directly to bacterial endotoxins. PMID- 3341914 TI - Computer-derived equations for predicting survival postoperatively. Their usefulness and limitations. AB - We used multivariate analysis to determine whether survival following perforations of the gastrointestinal tract could be accurately predicted from preoperative data. Of 12 variables tested, four were found to have predictive value. These were age, pulmonary disease, preoperative shock, and the attending surgeon. When these four variables were employed in a logistic regression equation on 42 patients, it correctly predicted which 21 patients died before leaving the hospital. To produce an equation useful for other hospitals, we recalculated it without the attending surgeon variable. Again, the equation was used to predict survival. The correlation of predicted vs observed outcome remained high, and, using a 2 x 2 chi 2 test, the correlation was significant. We then cross validated the three-variable model on data from a second hospital. The model accurately predicted the new data equally well. We believe that predictive models can identify risk factors in a variety of patient populations and can determine who is likely to benefit from specific treatment modalities. PMID- 3341915 TI - Septicemia from biliary tract infection. AB - One hundred four strains of microorganisms were isolated from the blood in 76 episodes of septicemia originating from biliary tract infection. The 70 patients involved included 40 with acute cholecystitis without previous surgery, 17 with cholangitis following previous surgery, and 13 patients with malignant disease, with or without previous surgery. The most common organisms were Escherichia coli, Klebsiella, Streptococcus, and Proteus. Various streptococci, most of them from group D, were involved in 21% of the episodes. Twenty-five patients underwent surgery following the bacteremia. In ten of 12 operations performed shortly after the septicemia, bile culture yielded the same organism(s) as in the blood. The types of organisms in blood, and especially the important role of streptococci, must be taken into consideration when choosing antibiotics for therapy for and prevention of biliary septicemia. PMID- 3341916 TI - Gastritis cystica polyposa. AB - Gastritis cystica polyposa was diagnosed in five patients between ages 29 and 61 years. All five had been operated on for peptic ulcer disease three to 26 years earlier, when gastroenteric anastomoses had been made. The presenting complaint was abdominal pain, nausea and vomiting, or gastrointestinal bleeding. The lesions, located on the gastric side of the anastomosis, consisted of polypoid mucosal changes associated with hyperplasia and cystic dilatation of glands. Radiologic and endoscopic findings were often nondiagnostic, and surgical intervention was necessary to relieve obstruction and to rule out carcinoma. Resection of the gastrojejunostomy site and choosing anastomotic techniques to minimize bile reflux into the stomach appear to be the preferred methods of treatment. PMID- 3341917 TI - Emphysematous pyelonephritis in a xanthogranulomatous kidney. An unusual cause of pneumoperitoneum. AB - Emphysematous pyelonephritis is a rare, life-threatening suppurative infection of the renal parenchyma and perinephric tissues. The disease is encountered primarily in patients with diabetes mellitus or ureteral obstruction associated with perinephric and intrarenal gas. Causative organisms are those normally found in the urinary and gastrointestinal tracts; however, anaerobic bacteria have been demonstrated in only 1% of cases. We describe a case of emphysematous pyelonephritis, which presented as an acute abdomen with pneumoperitoneum in a nondiabetic patient. No visceral injury was found at laparotomy. Multiple gas producing organisms, including Clostridium ramosum (not previously reported, to our knowledge), were the cause of the free intraperitoneal and perinephric air. Subsequent radical nephrectomy revealed a xanthogranulomatous kidney. An aggressive surgical approach combined with intensive antibiotic therapy, after aerobic and anaerobic culture of excised tissue, is lifesaving. PMID- 3341918 TI - Total pharyngeal reconstruction using a pectoralis major myocutaneous tunnel. AB - Total pharyngeal reconstruction was performed using a pectoralis major myocutaneous flap. In this technique, the posterior wall of the neopharynx consists only of the prevertebral tissue, while the flap forms the anterior and lateral walls. The posterior wall heals by reepithelialization of the prevertebral fascia. Clinical experience with seven patients has shown that this technique provides a wide conduit and is not prone to develop stenosis. PMID- 3341919 TI - Intestinal ischemia induced by cocaine abuse. PMID- 3341920 TI - Esophageal rupture secondary to passage of a gastric bubble for weight control. PMID- 3341921 TI - Flexible sigmoidoscopy and inguinal hernias. PMID- 3341922 TI - Isolation and characterization of caliciviruses from dogs with vesicular genital disease. AB - Two virus isolates, one from lesions of the vagina of a Bearded Collie and the other from the penis and prepuce of a Black Labrador, were partially characterized. The two viruses possessed the physicochemical properties, size and morphology of viruses belonging to the family Caliciviridae. The two isolates were shown by cross neutralization tests to be distinct from previously reported canine and feline caliciviruses. The viruses, isolated four years apart, are antigenically related. Additional studies are necessary to determine whether they are two distinct viruses or strains of another serotype belonging to the caliciviruses of the canine species. PMID- 3341924 TI - Forced normalization. PMID- 3341925 TI - Spontaneous dissection of the internal carotid artery. PMID- 3341923 TI - Inhibition of rabies virus infection by a soluble membrane fraction from the rat central nervous system. AB - This paper describes the inhibitory effect of a normal rat brain solubilized membrane preparation (RBSM-liposomes) on rabies virus infection. Rabies virus was incubated with RBSM-liposomes or their separated components (proteins, phospholipids, gangliosides) before infection of CER or neuroblastoma cells. In addition, both RBSM-liposomes and target cells were treated with enzymes prior to the infection step. All these experimental procedures showed that the active components were mainly lipids. PMID- 3341926 TI - 'Leuko-araiosis' and dementia. PMID- 3341927 TI - Leuko-araiosis in severe amyloid angiopathy. PMID- 3341928 TI - Why not Binswanger's disease? PMID- 3341930 TI - Ocular counterrolling abnormalities in spasmodic torticollis. AB - Spasmodic torticollis is a focal dystonic movement disorder of unknown origin, long hypothesized to have some vestibular involvement. An examination of otolith function, ocular counterrolling, was performed on eight patients with this disorder. The test consisted of photographing both eyes while the subject underwent rotation in both naso-occipital and earth-horizontal long axes. Measurements of eye torsion were made with a superimposition technique accurate to 0.1 degrees. Results showed all eight patients had abnormal ocular counterrolling. The most notable defect was the lack of sustained eye torsion at the extreme positions, resulting in rolling of the eyes in the direction of head tilt rather than counterrolling, a phenomenon previously observed only in persons with known brain-stem problems. That finding, as well as the majority of the patients showing spontaneous vestibular nystagmus in the dark and directional preponderance with caloric stimulation, implies that one difficulty in spasmodic torticollis lies in central vestibular connections, manifested by disruption of brain-stem pathways. PMID- 3341929 TI - Confusional states following posterior cerebral artery infarction. AB - Four patients with left-sided posterior cerebral artery infarction developed acute confusional states. Fifteen additional patients with confusion following unilateral posterior cerebral artery infarction were identified from a review of the literature; in 14 the lesion was left sided. Destruction or disconnection of dominant hemisphere neocortex from limbic structures, resulting in impairment of focal attention, loss of linguistically organized memory, and/or disruption of temporal sequencing may be responsible for this syndrome. PMID- 3341931 TI - Brain-stem auditory-evoked potentials in spasmodic torticollis. AB - The pathophysiology of idiopathic spasmodic torticollis is uncertain. Cerebral, basal ganglia, brain-stem, and cervicomedullary lesions have been implicated. Some investigators have found evoked-potential abnormalities, while others have not. We recorded brain-stem auditory-evoked potentials in six patients with otherwise normal result of examinations and laboratory studies. Brain-stem auditory-evoked potentials were recorded from Cz-A1 and Cz-A2 with rarefaction clicks delivered at 11.1/s and 70 dB above sensory threshold with 40-dB contralateral masking. Analysis time was 10 ms, filter bandpass was 150 to 3000 Hz, and 4000 averages were replicated. Patients and age-matched controls were compared by Student's t test. One patient had I-III and I-V interpeak latencies (IPLs) beyond clinical norms (99% tolerance limit). Mean IPLs ipsilateral to torticollis were 2.32 +/- 0.2 (I-III), 1.96 +/- 0.4 (III-V), and 4.16 +/- 0.3 (I V). Contralateral IPLs were 2.0 +/- 0.2 (I-III), 2.0 +/- 0.2 (III-V), and 3.9 +/- 0.5 (I-V). Control values were 2.04 +/- 0.2 (I-III), 1.86 +/- 0.2 (III-V), and 3.86 +/- 0.4 (I-V). Absolute latencies, V/I amplitude ratios, and III-V IPLs did not differ significantly between patients and controls, nor did IPLs contralateral to torticollis. Ipsilateral I-III and I-V IPLs were greater in patients than in controls. These findings are consistent with those of some clinical reports and with experimental evidence that brain-stem lesions produce torticollis. They imply brain-stem dysfunction ipsilateral to head deviation in at least some patients with torticollis. PMID- 3341932 TI - Hypertension. A neural disease? PMID- 3341934 TI - Neurogenic hypertension. PMID- 3341933 TI - The brain and hypertension. PMID- 3341935 TI - International symposium on early dopamine agonist therapy of Parkinson's disease. PMID- 3341936 TI - Seizure control with clomiphene therapy. A case report. AB - Clinical seizures ceased during six months of clomiphene citrate therapy in a 36 year-old man who had hypogonadotropic hypogonadism, reproductive dysfunction, and a 16-year history of regular seizures. Seizures recurred during the month that followed the discontinuation of clomiphene therapy. This apparent antiseizure effect of clomiphene is discussed in terms of three possible mechanisms of action: (1) Clomiphene may benefit seizures by raising serum levels of antiseizure medications. (2) Clomiphene may improve seizures by normalizing serum testosterone levels. (3) Clomiphene may act at a cerebral level to lessen seizures. A controlled investigation of the effects of clomiphene on epilepsy in the setting of reproductive dysfunction is suggested. PMID- 3341937 TI - Homozygous protein C deficiency in a newborn. Clinicopathologic correlation. AB - A rare case of homozygous protein C deficiency occurred in a newborn. The patient presented with purpura fulminans in the first few hours after birth and showed multiple hemorrhagic lesions on computed tomography of the brain at 5 days of age. Neurologic symptoms developed at two weeks and the patient died at 37 weeks. His protein C level was less than 5%. Autopsy revealed thrombosis of the dural sinuses, multiple cortical infarcts, intraparenchymal hemorrhages, and hydrocephalus. The pathologic findings are correlated with the neurologic deficits and previously documented cases are reviewed. PMID- 3341938 TI - Delayed traumatic midbrain syrinx. Clinical, pathologic, and electrophysiologic features. AB - Seven months following severe crushing closed-head trauma with initial excellent recovery, neurologic deficits referable to the right mesencephalon abruptly developed in a 28-year-old man. Computed tomography demonstrated a cystic midbrain lesion with apparent communication with the aqueduct (later confirmed at autopsy). Brain-stem auditory evoked potentials after the clinical deterioration showed depression of amplitude of wave V, compared with predeficit records, only when the ear contralateral to the brain-stem lesion was stimulated. PMID- 3341940 TI - The flight-of-colors test in multiple sclerosis. PMID- 3341939 TI - Brain death determination by angiography in the setting of a skull defect. AB - The absence of cerebral blood flow is presently considered the most reliable ancillary test in diagnosing brain death. A patient with an open skull fracture who met all criteria for brain death, including confirmatory postmortem studies, had a cerebral angiogram that showed unilateral preservation of cerebral circulation with diffuse extravasation of contrast material. We conclude that a skull defect may result in pressure reduction within the cranial cavity and persistent ipsilateral cerebral circulation, even after brain death. In this setting, diffuse extravasation of contrast material on angiography may reflect diffuse autolysis and suggest the diagnosis of brain death. PMID- 3341941 TI - Reflex sympathetic dystrophy. PMID- 3341942 TI - Chronic human colchicine myopathy and neuropathy. PMID- 3341943 TI - Ataxic hemiparesis from cysticercosis. PMID- 3341944 TI - Association of stiff-man syndrome and type I diabetes with islet cell and other autoantibodies. PMID- 3341945 TI - Wilson's disease. PMID- 3341946 TI - Mood disorder in multiple sclerosis. PMID- 3341947 TI - Anomalous cerebral asymmetries in acquired immunodeficiency syndrome. PMID- 3341948 TI - Bilateral symmetry of morphologic lesions in Alzheimer's disease. AB - We studied 16 brains of patients with Alzheimer's disease for left-right differences, or similarities, in the density of senile plaques (SPs) or neurofibrillary tangles (NFTs). Counts were made of SPs and NFTs on the left and right side of five different brain areas, which included middle frontal, superior temporal, the prosubiculum of the hippocampus (HPR), the entorhinal cortex of the hippocampus (HEN), and the basal nucleus of Meynert. The density of SPs was bilaterally symmetrical in all regions except the basal nucleus of Meynert in which technical problems may have occurred in sampling. In contrast to SPs, the density of NFTs was bilaterally symmetrical in both neocortical regions (middle frontal, superior temporal), but not in either hippocampal region (HPR, HEN). The absence of bilateral symmetry for the density of NFTs in the hippocampus, where the density of SPs was highly symmetrical, suggests that there may be a different pathogenesis for these lesions in Alzheimer's disease. The lack of a significant correlation between SP and NFT density within four of five regions, including HPR and HEN, also supports this suggestion. PMID- 3341949 TI - Bilateral symmetry of cholinergic deficits in Alzheimer's disease. AB - The specific activities of the cholinergic enzymes, choline acetyltransferase and acetylcholinesterase, as well as the density of muscarinic binding sites, were determined in five corresponding left and right regions of 16 brains obtained at autopsy from patients with histologically confirmed Alzheimer's disease. While a significant proportion of the individual specimens exhibited left-right asymmetries in cholinergic deficits, bilateral symmetry was the rule for frontal and temporal cortex, basal nucleus, and the prosubiculum of the hippocampus. In contrast to these four regions, left-right asymmetries in choline acetyltransferase activity and muscarinic receptor density appeared to be typical in the entorhinal cortex of the hippocampus. PMID- 3341950 TI - An estimate of the prevalence of dementia in idiopathic Parkinson's disease. AB - A review of the records for evidence of dementia using criteria adapted from the third edition of the Diagnostic and Statistical Manual of Mental Disorders in every patient (hospitalized and outpatient) with parkinsonism at a major medical center during an 18-month period revealed an overall prevalence of 10.9% in 339 patients with idiopathic Parkinson's disease. Demented patients were older, had a later age at onset of motor manifestations, and a more rapid progression of physical disability than nondemented patients. Duration of illness and levodopa use and the presence of tremor or depression were similar in demented and nondemented patients. Demented patients more often responded poorly or developed adverse effects to levodopa than nondemented patients. When Parkinson's disease began after age 70 years, dementia was noted over three times more frequently than when the disease began at an earlier age. The age-specific prevalence rate of dementia for patients older than 70 years was more than twice that for younger patients. Moreover, the number of records with evidence for dementia with idiopathic Parkinson's disease was 3.75 times greater than expected in comparison with data from a study of the prevalence of dementia in the elderly. PMID- 3341951 TI - Neuropsychological function in Alzheimer's disease. Pattern of impairment and rates of progression. AB - Although patients with Alzheimer's disease (AD) generally have impairments in multiple areas of cognitive function, there are those patients who appear to have neuropsychological deficits more prominent in one domain than in other domains. We examined the neuropsychological status of 86 patients with probable AD and 92 elderly control subjects and identified the patterns of impairments in the patients with AD. Independent deficits of visuoconstructional and lexical/semantic abilities were identified in a subset of patients by a principal components analysis. Individual patients were identified who were predominantly impaired in one, but not the other, neuropsychological domain. There were no striking relationships between the demographic characteristics of the patients and their pattern of deficits at the initial evaluation. There were no significant differences in age at onset or rate of progression of dementia among patients with different patterns of cognitive dysfunction. A review of the results of this and other studies suggests that the language impairment in AD may be associated with two distinct neuropsychological abnormalities: a lexical/semantic impairment that is unrelated to onset or progression of symptoms, and a syntactic impairment that may be associated with earlier onset and more rapid progression of dementia. PMID- 3341952 TI - Slowed information processing in multiple sclerosis. AB - Sixteen patients with a definitive diagnosis of multiple sclerosis (MS) and an equal number of matched controls were administered tests of memory and information processing speed. Results indicated a significant long-term verbal memory impairment in patients with MS, with spared short-term memory and memory scanning. Speed of information processing was evaluated with the Paced Auditory Serial Addition Test. The results for the two highest rates of presentation revealed significantly impaired processing in the MS group. Performance at the higher rates and retrieval of information from long-term memory were significantly correlated. These results suggest that slowed information processing is a deficit that contributes to long-term memory impairment in patients with MS. PMID- 3341953 TI - Weakness of the lower extremity in carotid occlusive disease. AB - Nineteen patients experienced progressive or episodic weakness of one lower extremity caused by severe stenosis or occlusion of the internal carotid artery. The majority of patients (84.2%) had occlusion or severe stenosis at the origin. Based on clinical profiles, angiographic findings, and cerebral blood flow patterns, we concluded that the pathophysiologic mechanism was hypoperfusion in the border zone between the anterior cerebral artery and the middle cerebral artery and that patients with progressive weakness had more extensive compromise in cerebral circulation. Following surgical treatment in 17 patients, progressive and episodic weakness disappeared and the majority of them (76.4%) became asymptomatic. However, the patients with stenosis at the siphon and those with progressive weakness from occlusion at the origin appeared to be at increased risk for cardiac death. PMID- 3341954 TI - Magnetic resonance imaging in young adults with cerebral infarction due to moyamoya. AB - The number, size, and location of cerebral infarctions, and blood flow in the middle cerebral artery as seen on proton magnetic resonance imaging were assessed in six white adults with angiographically documented moyamoya. Findings were correlated with clinical presentation, computed tomography, and angiography. Large hemispheric infarctions were found in five hemispheres, predominantly in watershed regions. Subcortical infarctions (n = 56) were found in all hemispheres. They were predominantly located in the centrum semiovale, in the distal beds of supply of the penetrating branches of the anterior and middle cerebral arteries. Infarction of the putamen was found in three hemispheres, caudate nucleus in four, globus pallidus in two, and anterior limb of the internal capsule in two. There were none in the posterior limb of the internal capsule, thalamus, brain stem, or cerebellum. Middle cerebral artery flow was visualized as a signal-void flow sign in only three hemispheres. Cerebral infarctions due to moyamoya are bilateral, multiple, often small, and asymptomatic, affecting predominantly the carotid circulation in watershed regions. Subcortical infarctions in the centrum semiovale and large hemispheric infarctions in hemodynamically compromised areas are the predominant findings. PMID- 3341955 TI - Limited relapse in Guillain-Barre syndrome after plasma exchange. AB - Ten of 94 consecutive patients with acute Guillain-Barre syndrome treated with plasma exchange relapsed after initial improvement. Deterioration occurred five to 42 days after the first series of exchanges, was usually mild, and in eight re treated patients, responded to a second series of plasma exchanges. None developed chronic inflammatory demyelinating polyneuropathy. The initial exchanges began three to 22 days (mean, 11 days and ended 14 to 27 days (mean, 19 days after the onset of illness. The biphasic course on these patients with limited relapses suggests that plasma exchange removes a circulating factor that continues to be active if treatment is stopped too early. Re-treatment with a second, and sometimes a third, series of plasma exchanges may be affective. PMID- 3341956 TI - Somatosensory evoked potentials in chronic alcoholics with spasticity. AB - Somatosensory evoked potentials to median and bilateral tibial nerve stimulation were investigated in eight chronic alcoholics with spasticity, 12 patients with alcoholic polyneuropathy, and 11 normal subjects. Central conduction velocities from the third lumbar vertebra to the fifth cervical vertebra and from the 12th thoracic vertebra to the fifth cervical vertebra were significantly lower in the chronic alcoholics with spasticity than in the alcoholic polyneuropathy group and in the healthy nonalcoholic group. The result indicates that chronic alcoholics with spasticity have conduction disturbance in the posterior column and/or the medial lemniscus, which is considered to be due to alcoholic myelopathy and/or a brainstem lesion. PMID- 3341957 TI - Concerning right-hemisphere dominance for affective language. PMID- 3341958 TI - Prosody and brain lateralization. Fact vs fancy or is it all just semantics? PMID- 3341959 TI - Prosody and brain lateralization. PMID- 3341960 TI - Early Alzheimer's disease. Diagnostic considerations. AB - An 82-year-old cognitively healthy man was assessed longitudinally until very mild senile dementia of the Alzheimer type was diagnosed by clinical research criteria and documented by psychometric testing at age 85 years. Four months after diagnosis, Alzheimer's disease was confirmed neuropathologically. The diagnostic difficulties involved in distinguishing early senile dementia of the Alzheimer type-Alzheimer's disease from normal aging are examined and clinical and pathologic features useful for their discrimination are discussed. PMID- 3341961 TI - Paraneoplastic optic neuritis and encephalomyelitis. Report of a case. AB - A 63-year-old man developed bilateral paresis of horizontal and upward eye movements. He was found to have a small oat cell carcinoma of the lung. Four months later he experienced acute visual blurring on the right side. Examination of the right eye at that time revealed a visual acuity of 3/200 and a central scotoma. There was swelling of the right optic disc. Three weeks after the onset of the visual loss, the acuity of the right eye spontaneously improved to 20/60, the field deficit lessened, and there was a decrease in the swelling of the optic disc. Subsequently, his neuro-ophthalmologic condition remained unchanged but his general health deteriorated, and he died nine months after the onset of the disease. Neuropathologic examination showed mild perivascular lymphocytic infiltration and fibrosis of the meninges throughout the central nervous system, loss of neurons and gliosis in the third and fourth cranial nerve nuclei, perivascular inflammation and gliosis of the optic nerves, and chiasm and central demyelination of the right optic nerve. No tumor cells were seen. These findings were consistent with a diagnosis of paraneoplastic optic neuritis and paraneoplastic encephalomyelitis. The present case confirms the existence of paraneoplastic optic neuritis and illustrates the clinical course of the disease. PMID- 3341962 TI - Drug-induced alzheimerism. AB - A 74-year-old man with parkinsonism developed progressive cognitive and behavioral dysfunction suggesting coexistent Alzheimer's disease. The intellectual and behavioral disturbances were reversed following withdrawal of his anticholinergic antiparkinsonian medication. This case demonstrates that anticholinergic drugs used to treat parkinsonism may mimic or exacerbate the clinical signs of Alzheimer's disease and suggests that these medications should be withdrawn for all parkinsonian patients who develop significant impairments of cognition or behavior. PMID- 3341963 TI - Contact lens-induced epithelial dendriform configurations. PMID- 3341965 TI - Malpractice litigation and cataract surgery. PMID- 3341966 TI - Mechanisms of pupillary block. PMID- 3341964 TI - Arcuate retinal folds after intraocular gas injection. PMID- 3341967 TI - Basal cell carcinoma masquerading as ectropion. Case report. PMID- 3341968 TI - Allergic response to a porcine collagen corneal shield. Case report. PMID- 3341969 TI - Total punctate keratopathy due to dipivefrin. Case report. PMID- 3341970 TI - Group G streptococci as a cause of bacterial endophthalmitis. Case report. PMID- 3341972 TI - Macular degeneration. Is there a nutritional component? PMID- 3341971 TI - Familial intracranial aneurysm presenting as a subtle stable third nerve palsy. Case report. PMID- 3341973 TI - Peripheral anterior synechiae formation after trabeculoplasty. AB - Argon laser trabeculoplasty (ALT) was performed on 60 eyes with primary open angle glaucoma and 59 eyes with capsular (pseudoexfoliation) glaucoma. Laser applications of four different power levels (500, 600, 700, and 800 mW) were directed either at the anterior trabecular meshwork or at the posterior trabecular meshwork. Gonioscopic examination to reveal peripheral anterior synechiae (PAS) formation was performed before and six months after ALT. Peripheral anterior synechiae were found in 26 (22%) of the eyes. With 500-mW laser power and anterior trabecular meshwork burns, no PAS developed. With 800-mW posterior trabecular meshwork burns, PAS developed in 12 (40%) of the eyes. No correlation between PAS formation and sex, age, glaucoma type, preoperative antiglaucoma medication, pigmentation of the chamber angle, and visible burn effect was found. Intraocular pressure decrease after ALT was significantly smaller in eyes with PAS. PMID- 3341974 TI - Surgical results in iridocorneal endothelial syndrome. AB - The charts of 83 patients with iridocorneal endothelial (ICE) syndrome were retrospectively reviewed. Forty-two eyes of 42 patients had had filtering surgery, 37 of whom had had a trabeculectomy to reduce uncontrolled intraocular pressure. Twenty-four of these trabeculectomy patients required a second surgery, and 8 required a third surgery. The results are presented using a survival analysis. The success rates at one year of follow-up for the first, second, and third trabeculectomies were 64%, 79%, and 63%, respectively. Patients subclassified as having Chandler's syndrome, essential iris atrophy, and Cogan Reese syndrome responded with approximately the same success rates within the first two years following their first surgery. The success rates for repeated surgeries are comparable with those of initial surgery in patients with primary open angle glaucoma. On the basis of this study, further surgery is recommended despite initial failure in this group of difficult patients. PMID- 3341976 TI - Magnetic resonance imaging in pituitary apoplexy. AB - The diagnosis of pituitary apoplexy, an often-fatal disorder, is frequently delayed. Computed tomographic (CT) scanning has been shown to be useful in the detection of pituitary apoplexy; however, the value of magnetic resonance imaging (MRI) is yet to be determined. The MRI and CT scans of three consecutive and histopathologically proved cases of pituitary apoplexy were reviewed. The MRI scans obtained at least five days after the onset of symptoms suggested pituitary apoplexy (hemorrhage) in all three cases, while CT scanning indicated pituitary hemorrhage in only one case. Increased signal on the T1-weighted image was the hallmark on MRI scans in all three cases. These findings suggest that MRI scanning may be superior to CT scanning in identifying pituitary apoplexy, at least in the subacute phase. PMID- 3341975 TI - Peripheral visual field testing by automated kinetic perimetry in glaucoma. AB - The peripheral visual field was measured with a single kinetic target and the central 30 degrees with static stimuli in 600 eyes of 323 patients with glaucoma and patients suspected of having glaucoma using an automated perimeter (Fieldmaster 5000). The purpose of the study was to compare the additional information gained by the peripheral field testing against the time requirement for this extra procedure. An abnormal peripheral field supported the diagnosis suggested by a central abnormality in 131 eyes (21.8%), while a defect in the peripheral field provided the principal diagnostic information, when the central field was normal or equivocal, in 25 cases (4.2%). Peripheral field measurements accounted for approximately 28% of the total testing time. PMID- 3341977 TI - Early changes in refractive error following radial keratotomy. AB - One hundred twenty-six eyes that had undergone radial keratotomy were analyzed to assess the early changes in refractive error after surgery. Between two weeks and three months, 38% of eyes became more myopic by less than 1 diopter (D), 34% by 1.00 to 1.87 D, and 25% by 2.00 to 3.50 D. Four eyes (3%) had a decrease of 0.25 to 1.25 D. The average increase between two weeks and three months was 1.31 D (SD, 0.9 D). To decrease this change, 15 eyes were semi-pressure patched at night and treated with topical steroids for four weeks following surgery. The average change between two weeks and three months in these eyes was 0.3 D (SD, 1.0 D). This retrospective study suggests that semi-pressure patching after surgery may be useful for eyes that are undercorrected or overcorrected by less than 1 D. PMID- 3341978 TI - In vitro melanoma cell growth after preenucleation radiation therapy. AB - The in vitro efficacy of 20 Gy (2000 rad) of external beam irradiation delivered to patients with choroidal melanomas prior to enucleation was investigated in 11 patients whose tumors were grown in cell culture. Phase-contrast microscopy was used to compare growth patterns between irradiated and nonirradiated tumors. Cell types were determined by histologic stains, and electron microscopy identified intracytoplasmic melanin. Irradiated melanomas did not grow and did not attach to culture flasks, thus demonstrating that preenucleation irradiation alters the in vitro growth of melanoma cells. PMID- 3341979 TI - Ophthalmic observations in lecithin cholesterol acyltransferase deficiency. AB - Lecithin cholesterol acyltransferase is an enzyme that esterifies free cholesterol. A complete deficiency of this enzyme results in a diffusely cloudy cornea. This deficiency is thought to be transmitted as an autosomal recessive trait. We studied a family in which four members were homozygote recessive. In the homozygote recessive condition, a central corneal haze caused by deposition of numerous minute gray dots was consistently present. In the heterozygote condition, arcuslike changes were present in some of the patients studied. We found the corneal change in the recessive state to be sensitive and specific as a marker of this condition. Heterozygotes appear to have a higher incidence of arcuslike corneal changes. PMID- 3341981 TI - Necrotic changes of choroidal melanocytes in sympathetic ophthalmia. AB - There are various theories as to the origin of epithelioid cells in the choroid with sympathetic ophthalmia. Some investigators propose a transformation of choroidal melanocytes as the origin, and others suggest a histiomonocytic derivation. One reason this controversy exists may be the relative lack of investigations into necrotic changes of choroidal melanocytes. The structural alterations in the choroidal melanocytes of an injured eye with sympathetic ophthalmia were studied, and the sequence of events involved in degeneration and necrotic changes were elucidated. The damaged melanocytes developed vacuolation, and the melanin granules were gathered into autophagosomes or had disappeared. The nuclei of the severely damaged melanocytes became pyknotic. Degenerated cell nuclei were phagocytized by macrophages. It is concluded that choroidal melanocytes may not transform into epithelioid cells and that they disappear from the choroid following degeneration. PMID- 3341980 TI - Choroidopathy in systemic lupus erythematosus. AB - Choroidopathy in association with systemic lupus erythematosus (SLE) is a clinically unusual manifestation, previously described in only six patients, to our knowledge. We have followed up six patients with SLE and choroidopathy manifested by multifocal, serous elevations of the retinal pigment epithelium and sensory retina. In four patients, macular involvement was present, and they suffered visual loss. Two eyes of two patients progressed to large, bullous, exudative retinal detachments. In the three patients in whom control of the systemic disease was achieved, the serous detachments resolved. The pathogenesis is most likely related to choroidal vascular disease with resultant pigment epithelial damage and serous fluid leakage beneath the retina. PMID- 3341982 TI - Excimer laser keratectomy for myopia with a rotating-slit delivery system. AB - We performed argon fluoride excimer laser (193-nm) superficial keratectomy for myopia on human donor eyes and on a resected corneal disc. The laser beam was shaped by a rotating slit to produce a circular ablation 7.5 mm in diameter, with a mathematically defined profile to correct myopia. The fluence at the surface of the cornea was 200 mJ/cm2; the laser was fired at 20 Hz. Each 4.5-mJ laser pulse etched a 0.17-micron deep image of the slit in the cornea. Since the slit moved (0.03 Hz), each successive pulse etched an area adjacent to the previous one, reducing damage from repetitive pulses striking the same area. The slit scanned the cornea many times and the summation of these individual ablations produced the smooth myopic ablation profile, as shown by computerized keratographs and light and electron microscopy. PMID- 3341983 TI - Uses of thrombin in ocular surgery. Effect on the corneal endothelium. AB - Thrombin is a hemostatic factor that induces platelet aggregation and catalyzes the conversion of fibrinogen to fibrin. The potential for its increasing application to a variety of anterior and posterior segment surgery led us to investigate the in vitro effect of thrombin on the corneal endothelium in a sheep model. We examined freshly excised sheep corneas stained with alizarin red and trypan blue after exposure to two different concentrations of thrombin for four hours. The structure of the corneal endothelium appeared to be intact even after prolonged exposure to thrombin at concentrations of 100 and 1000 U/mL. Thrombin appears to be nontoxic to the corneal endothelium in this experimental model. PMID- 3341984 TI - Ocular dialysis. A new technique for in vivo intraocular pharmacokinetic measurements. AB - A new technique, using the principle of dialysis, enables continuous determination of the concentration of compounds within the vitreous humor of the eye. A semipermeable catheter inserted into the cat vitreous cavity was continuously perfused with a normal saline solution. Gentamicin concentration in the dialysate, after subconjunctival or intravitreal injection, was used to calculate gentamicin concentration in the vitreous from the catheter's recovery ratio, as calibrated in vitro. After subconjunctival injection, no gentamicin was detected in the vitreous for up to eight hours. From four to eight hours after intravitreal injection of approximately 100 micrograms of gentamicin sulfate, its vitreal concentration ranged from 30 to 80 mg/L and from nine to 16 hours it fell from 26 to 22 mg/L. This method may prove useful for the study of the pharmacokinetics of many drugs and metabolites in the eye. PMID- 3341985 TI - Detection and localization of nonmetallic intraocular foreign bodies by magnetic resonance imaging. AB - Computed tomography (CT) is useful in detecting metallic intraocular foreign bodies. Magnetic resonance imaging (MRI) is a technique that might allow the detection and localization of nonmetallic intraocular foreign bodies. We performed CT and MRI scans on ten freshly enucleated sheep eyes, eight of which contained nonmetallic intraocular foreign bodies of wood, glass, plastic, or rock. Computed tomography correctly detected seven of eight foreign bodies, while MRI detected all eight of the foreign bodies. Computed tomography is necessary to determine the presence of a metallic foreign body, but when the CT scan is negative, MRI may still detect small nonmetallic foreign bodies. PMID- 3341986 TI - Pituitary apoplexy. PMID- 3341987 TI - Epidermal cysts of the eyelid. PMID- 3341988 TI - Hypodermic stainless steel tacks and companion inserter designed for peripheral fixation of retina. AB - Mechanical fixation of the torn or cut edge of retina with 30-gauge hypodermic stainless steel tacks has been performed in 15 patients at the Bascom Palmer Eye Institute, Miami, and Miami Veterans Administration Medical Center with six to 18 months of follow-up. The companion tack inserter allows the surgeon to select an angle for the shaft of the tack in relation to the inserter to allow the tack to be driven perpendicularly into sclera even when the insertion is anterior to the equator. If residual detachment remains following fluid-gas exchange after preliminary placement of the retinal tacks, a given tack may be removed and reinserted to facilitate complete retinal reattachment. This utilitarian feature allows the surgeon to eliminate residual anteroposterior traction following complete membrane peeling by extending relaxing retinotomies and tacking the posterior cut edge of the retina securely between the ora serrata and the equator. PMID- 3341989 TI - Effects of saturated and polyunsaturated dietary fat on the concentrations of HDL subpopulations in African green monkeys. AB - The effect of the type of dietary fat on the concentrations and compositions of high density lipoprotein (HDL) subpopulations was studied in groups of African green monkeys consuming 40% of calories as fat supplied as saturated fat (P/S = 0.3) or polyunsaturated fat (P/S = 2.2) in the presence of either 0.8 mg or 0.03 mg cholesterol/kcal. Plasma HDL cholesterol concentrations were lower in polyunsaturated fat-fed animals. The distribution of mass among HDL subfractions was assessed by analytic ultracentrifugation (AnUC), density gradient ultracentrifugation (DGUC), and polyacrylamide gradient gel electrophoresis (GGE). This made it possible to characterize and quantitate the HDL subpopulations HDL2b, HDL2a, HDL3a, HDL3b, and HDL3c (arranged in order of decreasing particle size and decreasing cholesterol content). Polyunsaturated fat fed animals had lower concentrations of the large, cholesterol-rich HDL2b subpopulation, as well as higher concentrations of intermediate size HDL (HDL2a and HDL3a on the high cholesterol diet; HDL3a and HDL3b on the low cholesterol diet). Consistent with the observed fat-related redistribution of HDL mass, the saturated fat-fed monkeys had higher apo A-I/apo A-II ratios. The larger HDL often contained detectable apo E; however, the concentration of apo E in HDL was low in both saturated and polyunsaturated fat-fed animals. Thus, compared to saturated fat, dietary polyunsaturated fat induced the formation of smaller size HDL subpopulations and, therefore, an overall lower cholesterol content per particle for plasma HDL. PMID- 3341991 TI - Effect of metoprolol on diet-induced atherosclerosis in rabbits. AB - The effect of metoprolol, a beta 1-blocker, on atherogenesis was evaluated in rabbits fed a diet supplemented with 0.25% cholesterol and 3% coconut oil for 21 weeks. After 7 weeks on the diet, the rabbits were randomly divided into treated (n = 22) and untreated (n = 22) groups. Treated animals received metoprolol subcutaneously by an osmotic pump for 14 weeks, resulting in a plasma level of 774 +/- 69 nM during the investigation. Plasma concentrations of cholesterol, triglycerides, and phospholipids did not differ between the two groups. Nor were there any significant differences between the two groups in plasma concentrations of apolipoprotein A-I, apolipoprotein B, apolipoprotein C-III, and apolipoprotein E measured by electroimmunoassay. At the end of the study, the aortas were cut into three portions and the extent of atherosclerosis was determined by morphometry. The group that had received metoprolol had significantly (p less than 0.015) less atherosclerosis in the aorta (ascending plus arch 37.8 +/- 6.8%, thoracic 32.9 +/- 6.1%, abdominal 19.8 +/- 6.1% of total intimal area; mean +/- SEM) than the controls (ascending plus arch 54.9 +/- 7.1%, thoracic 48.0 +/- 6.2%, abdominal 25.9 +/- 5.5%). PMID- 3341990 TI - Effects of selective breeding on the cholesterolemic responses to dietary saturated fat and cholesterol in baboons. AB - Positive assortative mating of baboons (Papio sp.) based on elevation of serum cholesterol concentrations in response to a cholesterol- and saturated fat enriched diet produced 64 progeny (30 high line; 34 low line). When the animals were 3 to 4 years of age, we tested their lipoprotein cholesterol responses to dietary cholesterol and fat in a factorial experiment with two levels of dietary cholesterol (1.7 and less than 0.01 mg/kcal) and two types of fat, coconut oil (P/S 0.1) and corn oil (P/S 3.5), each providing 40% of total calories from fat; we also tested their responses to chow. The high line animals had significantly higher very low density plus low density lipoprotein (VLDL + LDL) and high density lipoprotein (HDL) cholesterol levels on all diets. The effects of dietary cholesterol on VLDL + LDL cholesterol concentrations were greater in high line animals than in low line animals, but dietary cholesterol's effects on HDL cholesterol were similar in both lines. The effects of saturated fat, compared to unsaturated fat, on both VLDL + LDL and HDL cholesterol levels were similar in both lines. Selective breeding produced lines diverging in lipoprotein cholesterol concentrations by acting on several different genetically mediated processes that control serum lipoprotein levels. At least one of these processes involves responsiveness of serum VLDL + LDL cholesterol concentration to dietary cholesterol. PMID- 3341992 TI - Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. II. Characterization of intracellular morphologic changes. AB - The effects of the slow Ca++ channel blocker, nifedipine, and ACAT inhibitor, octimibate, on cholesterol-loaded macrophages were compared at the ultrastructural level. The Ca++ antagonist induced the formation of membrane surrounded "lamellar bodies" originating from lysosomes. The macrophages secreted these lamellar bodies, which were rich in phospholipids and cholesterol, into the culture medium even in the absence of cholesterol acceptors. In contrast, the ACAT inhibitor induced the formation of lamellar bodies originating from lipid droplets, which were also surrounded by membranes. There is strong evidence that these latter membranes were newly synthesized at the margin of the lipid droplets by the endoplasmic reticulum. The lamellar bodies descending from lipid droplets after ACAT inhibitor treatment were not secreted by the cells. They were stored in the cytoplasmic compartment in the absence of high density lipoproteins (HDL). When HDL were added to the medium, the lamellar bodies specifically interacted with endosomes containing the internalized HDL particles and disappeared concomitantly with an enhanced HDL-mediated cholesterol efflux. From the biochemical data in the accompanying article and the morphological data here, we conclude that macrophages release cholesterol by two major pathways: 1) an HDL independent secretion of lamellar bodies containing cholesterol, which originate from lysosomes, and 2) an HDL-dependent release of cholesterol via the formation of lamellar bodies descending from lipid droplets, which intracellularly fuse with HDL-containing endosomes. The cholesterol-enriched HDL are then secreted as intact lipoproteins. PMID- 3341993 TI - Presence of a modified low density lipoprotein in humans. AB - Low density lipoproteins (LDL) collected from 18 fasting humans were subjected to ion exchange chromatography on DEAE Sepharose. By this procedure, a LDL subfraction was isolated with an electric charge more negative than the LDL bulk. This LDL appeared to be mainly characterized by low phospholipid content, high free cholesterol and protein content, low esterified/free cholesterol ratio, and a high content of conjugated dienes, particularly of cholesterol esters. This subfraction, in an amount ranging from 5% to 20% of total LDL, was characterized by the presence of apo B-100 and protein aggregates that were reactive to anti apo B monoclonal antibodies. Electron microscopy showed the more electronegative LDL to be heterogeneous in size with a tendency to aggregate. This LDL had low binding capacity with high affinity receptors of fibroblasts and low immunoreactivity with the monoclonal antibodies that recognize the receptor binding domain of apo B. Finally, the incubation of this LDL subfraction with cultured macrophages led to a higher increase in cellular cholesterol in spite of a lower rate of uptake as compared to the LDL bulk and to acetyl-LDL. The more electronegative LDL subfraction that we isolated for chemico-physical behavior and conjugated diene content may represent the peroxidized aliquot of human LDL. PMID- 3341994 TI - Body fat distribution, plasma lipids, and lipoproteins. AB - The relation of body fat distribution as measured by the ratio of waist to hip circumferences (WHR) to plasma levels of lipids and lipoproteins was studied in 713 men and 520 women who were employed by two Milwaukee companies. Quetelet index (kg/m2), waist girth, hip girth, and WHR were each positively related to levels of total cholesterol, triglycerides, apolipoprotein B, and the ratio of total to high density lipoprotein (HDL) cholesterol. In addition, the anthropometric measures were inversely associated with levels of HDL cholesterol. (Controlling for age, alcohol intake, exercise level, current smoking status, and oral contraceptive use only slightly reduced the strength of the correlations.) In addition, WHR and Quetelet Index were independently related to lipid and lipoprotein levels, and the magnitudes of the associations were roughly equivalent. For example, the mean (covariate-adjusted) triglyceride level among men in the upper tertile of the Quetelet Index was 37 mg/dl higher than for men in the lower tertile of the Quetelet Index; the corresponding difference according to WHR tertiles (upper to lower) was 39 mg/dl (p less than 0.01 for both effects). These findings indicate that in healthy men and women a less favorable lipid and lipoprotein profile is associated with elevated levels of both Quetelet Index and WHR. PMID- 3341995 TI - Workshop on the impact of dietary cholesterol on plasma lipoproteins and atherogenesis. PMID- 3341996 TI - Anxiety induced by false heart rate feedback in patients with panic disorder. PMID- 3341998 TI - Experimental analyses of panic--III. Claustrophobic subjects. PMID- 3341999 TI - Velten and musical mood induction procedures: a comparison with accessibility of thought associations. PMID- 3342000 TI - Phobias and preparedness: replication and extension. PMID- 3341997 TI - Experimental analyses of panic--II. Panic patients. PMID- 3342002 TI - A study of the hydration and thermodynamics of warm-water and cold-water fish collagens. AB - The hydrated volumes, Vh, of collagens extracted from various fish species were calculated by using the Simha-Einstein equation, and it was found that the hydration of warm-water fish collagen is greater than that of cold-water fish collagen (halibut). Although the intrinsic viscosities of warm-water fish (bigeye tuna, carp and catfish) collagens are almost the same, the hydrated volume of bigeye-tuna collagen is approx. 1.5 and 3 times those of carp and catfish collagens respectively. The extent of hydration at 20 degrees C is in the following order: bigeye tuna greater than carp greater than catfish greater than halibut. The various thermodynamic activation parameters (delta G*, delta H* and delta S*) were calculated and it was found that they are useful for determining the exact denaturation temperature. It was calculated that the denaturation temperatures of halibut, bigeye-tuna, carp and catfish collagens are 17, 31, 32 and 26-30 degrees C respectively. The variations of hydration, intrinsic viscosity, denaturation temperature and the thermodynamic parameters with the variation of concentration of catfish collagen were also thoroughly examined. The change of thermodynamic parameters from coiled-coil to random-coil conformation upon denaturation of collagen were calculated from the amount of proline and hydroxyproline residues and compared with viscometric results. PMID- 3342001 TI - The kinetics of transport of lactate and pyruvate into rat hepatocytes. Evidence for the presence of a specific carrier similar to that in erythrocytes. AB - Time courses of L-lactate and pyruvate uptake into isolated rat hepatocytes were measured in a citrate-based medium to generate a pH gradient (alkaline inside), by using the silicone-oil-filtration technique at 0 degrees C to minimize metabolism. At low concentrations of lactate and pyruvate (0.5 mM), transport was inhibited by over 95% by 5 mM-alpha-cyano-4-hydroxycinnamate, whereas at higher concentrations (greater than 10 mM) a significant proportion of transport could not be inhibited. The rate of this non-inhibitable transport was linearly related to the substrate concentration, was less with pyruvate than with L-lactate, and appeared to be due to diffusion of undissociated acid. Uptake of D-lactate was not inhibited by alpha-cyano-4-hydroxycinnamate and occurred only by diffusion. Kinetic parameters for the carrier-mediated transport process were obtained after correction of the initial rates of uptake of lactate and pyruvate in the absence of 5 mM-alpha-cyano-4-hydroxycinnamate by that in the presence of inhibitor. Under the conditions used, the Km values for L-lactate and pyruvate were 2.4 and 0.6 mM respectively and the Ki for alpha-cyano-4-hydroxycinnamate as a competitive inhibitor was 0.11 mM. Km values for the transport of L-lactate and pyruvate into rat erythrocytes under similar conditions were 3.0 and 0.96 mM. The Vmax. of lactate and pyruvate transport into hepatocytes at 0 degrees C was 3 nmol/min per mg of protein. Carrier-mediated transport of 0.5 mM-L-lactate was inhibited by 0.2 mM-p-chloromercuribenzenesulphonate (greater than 90%), 0.5 mM quercetin (80%), 0.6 mM-isobutylcarbonyl-lactyl anhydride (70%) and 0.5 mM-4,4' di-isothiocyanostilbene-2,2'-disulphonate (50%). A similar pattern of inhibition of lactate transport is seen in erythrocytes. It is suggested that the same or a similar carrier protein exists in both tissues. The results also show that L lactate transport into rat hepatocytes is very rapid at physiological temperatures and is unlikely to restrict the rate of its metabolism. Differences between our results and those of Fafournoux, Demigne & Remesy [(1985) J. Biol. Chem. 260, 292-299] are discussed. PMID- 3342003 TI - Desensitization and recovery of muscarinic and histaminergic Ca2+ mobilization in 1321N1 astrocytoma cells. AB - Intracellular free Ca2+ was monitored in suspensions of 1321N1 astrocytoma cells by using the Ca2+ indicator fura-2. The cytoplasmic Ca2+ concentration increased from 237 +/- 6 nM to 1580 +/- 170 nM within 3-5 s of addition of 300 microM carbachol. After the peak in response, the Ca2+ concentration diminished, establishing a new steady state in about 1 min that was approx. 150 nM above the previous baseline. Histamine increased cytoplasmic Ca2+ to about 40% of the maximal value seen with carbachol. In Ca2+-free buffer each agonist elicited a normal initial increase in cytoplasmic Ca2+, but the sustained portion of the response was abolished. The increase in Ca2+ in response to either carbachol or histamine could be completely inhibited by pretreating the cells with carbachol; the response to carbachol could be partially inhibited by pretreating the cells with histamine. The Ca2+ responses did not recover in the continued presence of carbachol. However, if the carbachol was washed out or if atropine was added after carbachol, the responses to agonist recovered in a time-dependent manner (half-time 3-4 min), and recovery depended on the presence of extracellular calcium. The results indicate that carbachol and histamine stimulate release of Ca2+ from the same intracellular Ca2+ store, that depletion of this store is responsible for heterologous desensitization between these two agonists, and that repletion of the agonist-sensitive Ca2+ pool does not occur in the continued presence of agonist or in the absence of extracellular Ca2+. PMID- 3342004 TI - Mechanism of the decrease in hexose transport by mouse mammary epithelial cells caused by fasting. AB - The basal carrier-mediated uptake of 0.5 mM-3-O-methylglucose by mammary epithelial cells from lactating mice was calculated to be 227 +/- 9 pmol/min per microgram of DNA (mean +/- S.E.M., n = 11). Fasting the mice for 16 h overnight resulted in a decrease in this rate to 65 +/- 4 pmol/min per microgram of DNA (n = 10). Refeeding the fasted mouse for 3 h before isolation of the cells restored the transport activity to 230 +/- 12 pmol/min per microgram of DNA (n = 12). The Vmax. for equilibrium exchange entry of 3-O-methylglucose by intact cells was decreased from 6.6 +/- 0.4 to 0.9 +/- 0.2 nmol/min per microgram of DNA (mean +/- S.E.M., n = 3) by fasting. The number of D-glucose-inhibitable cytochalasin-B binding sites in a plasma-membrane-enriched fraction of the cells was also decreased from 5.7 +/- 1.5 to 1.7 +/- 0.1 pmol/mg of membrane protein (mean +/- S.E.M., n = 3). Again, refeeding the fasted mouse for 3 h reversed both these effects. These results are consistent with a decrease in the number of functional glucose carriers in the plasma membrane of the mammary epithelial cells. Since the restoration of transporter activity after refeeding does not appear to require the synthesis of new protein, the effect of fasting probably involves not a loss of transporters, but a change in their orientation within the plasma membrane or a redistribution within the cell. PMID- 3342005 TI - Sodium-gradient-driven, high-affinity, uphill transport of succinate in human placental brush-border membrane vesicles. AB - Brush-border membrane vesicles isolated from normal human term placentas were shown to accumulate succinate transiently against a concentration gradient, when an inward-directed Na+ gradient was imposed across the membrane. This uptake was almost totally due to transport into intravesicular space, non-specific binding to the membranes being negligible. The dependence of the initial uptake rate of succinate on Na+ concentration exhibited sigmoidal kinetics, indicating interaction of more than one Na+ ion with the carrier system. The Hill coefficient for this ion was calculated to be 2.7. The Na+-dependent uptake of succinate was electrogenic, resulting in the transfer of positive charge across the membrane. Kinetic analysis showed that succinate uptake in these vesicles occurred via a single transport system, with an apparent affinity constant of 4.8 +/- 0.2 microM and a maximal velocity of 274 +/- 4 pmol/20 s per mg of protein. Uptake of succinate was strongly inhibited by various C4 or C5 dicarboxylic acids, whereas monocarboxylic acids, amino acids and glucose showed little or no effect. Li+ and K+ could not substitute for Na+ in the uptake process. Instead, Li+ was found to have a significant inhibitory effect on the Na+-dependent uptake of succinate. PMID- 3342006 TI - Formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Is haemoglobin a biological Fenton reagent? AB - The ability of oxyhaemoglobin and methaemoglobin to generate hydroxyl radicals (OH.) from H2O2 has been investigated using deoxyribose and phenylalanine as 'detector molecules' for OH.. An excess of H2O2 degrades methaemoglobin, releasing iron ions that react with H2O2 to form a species that appears to be OH.. Oxyhaemoglobin reacts with low concentrations of H2O2 to form a 'reactive species' that degrades deoxyribose but does not hydroxylate phenylalanine. This 'reactive species' is less amenable to scavenging by certain scavengers (salicylate, phenylalanine, arginine) than is OH., but it appears more reactive than OH. is to others (Hepes, urea). The ability of haemoglobin to generate not only this 'reactive species', but also OH. in the presence of H2O2 may account for the damaging effects of free haemoglobin in the brain, the eye, and at sites of inflammation. PMID- 3342007 TI - Synthesis of very long chain (up to 36 carbon) tetra, penta and hexaenoic fatty acids in retina. AB - The synthesis of very long chain (C24 to C36) polyunsaturated (four, five and six double bonds) fatty acids (VLCPUFA) is investigated in bovine retina using [14C]acetate. Saturates on the one hand (mainly palmitate), and polyenes on the other (mainly VLCPUFA), incorporate most of the label found in lipids. Phosphatidylcholine (PC) is the most highly labelled lipid class, since both types of 14C-labelled fatty acids, but especially this novel series of VLCPUFA, are concentrated in this phospholipid. Radioactivity from [14C]acetate is found in very long chain tetra, penta and hexaenoic fatty acids of PC. The labelling of 20:4(n - 6), 20:5(n - 3), 22:5(n - 6) and 22:6(n - 3) is much lower than that of longer polyenes of each of these series, indicating that VLCPUFA are synthesized in situ by successive elongations of the above polyenes, pre-existing in retina lipids. In various subcellular fractions isolated from retinas after incubations with [14C]acetate (including cytosol, microsomes, mitochondria and photoreceptor membranes), the labelling of the VLCPUFA of PC is very high, even at relatively short intervals of incubation. The results suggest that not only the synthesis but also the intracellular traffic among membranes of VLCPUFA-containing species of PC are very active processes in the retina. PMID- 3342008 TI - Enzymes of carnitine acylation. Is overt carnitine palmitoyltransferase of liver peroxisomal carnitine octanoyltransferase? AB - Liver mitochondria prepared by differential centrifugation are contaminated by significant quantities of peroxisomes and microsomal fractions. 'Easily solubilized carnitine palmitoyltransferase' prepared from liver mitochondria is thought to originate from the outer surface of the mitochondrial inner membrane. We have characterized the carnitine palmitoyltransferase activities of freeze thaw extracts of rat liver mitochondrial preparations. Chromatography on Sephadex G-100 yields two broad peaks of carnitine decanoyltransferase activity: one eluted at the end of the void volume, which can be removed (precipitated) by ultracentrifugation; the second peak represents the soluble activity and is eluted at an Mr near 70,000. The activity in the soluble peak is precipitated by an antibody raised against carnitine octanoyltransferase purified from mouse liver peroxisomes. In contrast, antibody raised against carnitine palmitoyltransferase purified from liver mitochondrial membranes had no effect (P. Brady & L. Brady, personal communication). The carnitine acyltransferase activities of the Mr-70,000 peak in the presence or absence of Tween 20 showed maximum activity with decanoyl-CoA and about one-third of this activity with palmitoyl-CoA, similar to peroxisomal carnitine octanoyltransferase. These data show that 7500 g preparations of liver mitochondria isolated by differential centrifugation are enriched by peroxisomal carnitine octanoyltransferase (approx. 20% of the protein of the fraction is peroxisomal) and indicate that this enzyme may be the one reported as 'overt' or 'easily solubilized' mitochondrial carnitine palmitoyltransferase. PMID- 3342009 TI - Distribution and properties of the glycylsarcosine-transport system in rabbit renal proximal tubule. Studies with isolated brush-border-membrane vesicles. AB - The distribution and properties of the peptide-transport system in rabbit renal proximal tubule was examined with glycylsarcosine as the substrate and using brush-border-membrane vesicles derived from pars convoluta (outer cortex) and pars recta (outer medulla). The dipeptide was transported into these vesicles against a concentration gradient in the presence of an inward-directed H+ gradient, demonstrating the presence of a H+-coupled peptide-transport system in outer-cortical as well as outer-medullary brush-border membranes. Even though the transport was electrogenic and was energized by a H+ gradient in both membranes, the system was more active in outer medullary membranes than in outer cortical membranes. Kinetic analysis showed that, although the affinity of the transport system for glycylsarcosine was similar in both membrane preparations, the capacity of the system was significantly greater in outer medulla than in outer cortex. In addition, the pH profiles of the peptide-transport systems in these membrane preparations also showed dissimilarities. The greater dipeptide uptake in one membrane vis-a-vis the other may probably be due to the difference in the affinity of the transport system for H+ and/or the difference in peptide/H+ stoichiometry. PMID- 3342010 TI - Developmental forms of human skeletal-muscle AMP deaminase. The kinetic and regulatory properties of the enzyme. AB - AMP deaminase isoforms from human skeletal muscle can be separated chromatographically [Kaletha, Spychala & Nowak (1987) Experientia 43, 440-443]. In adult tissue nearly all the AMP deaminase activity was eluted from phosphocellulose with 0.75 M-KCl ('adult' isoform), and the remaining activity could be eluted with 2.0 M-KCl. Conversely, most of the AMP deaminase activity from 11-week-old fetal tissue was eluted from phosphocellulose with 2.0 M-KCl ('fetal' isoform). In the present paper the kinetic and regulatory properties of AMP deaminase extracted from 11- and 16-week-old fetal skeletal muscle are reported. The two isoforms from 11-week-old human fetus differed distinctly in these properties. The 'fetal' isoform had about 5-fold higher half-saturation constant (S0.5) value than the 'adult' form. It was also more sensitive to the influence of some important regulatory ligands (ADP, ATP and Pi), and exhibited a different pH/activity profile. The 'adult' isoform of AMP deaminase from fetal muscle and the enzyme from mature muscle possessed similar kinetic and regulatory properties. This isoform seems not to be subject to any major modifications during further ontogenesis. This is not true, however, for the 'fetal' isoform. In the muscle of 16-week-old human fetus, the 'fetal' isoform showed a peculiar, biphasic, type of substrate-saturation kinetics. This phenomenon may reflect appearance of the next, developmentally programmed, isoform of human skeletal muscle AMP deaminase. PMID- 3342012 TI - Histidine decarboxylase from rat mast cells. Enhanced recovery in cell-free extracts and isotopic labelling. AB - A procedure for obtaining rat mast-cell histidine decarboxylase in greater than 50% yield in cell-free extracts was developed. The enzyme was found in the supernatant fractions from a 3,500 g and a 105,000 g centrifugation step and was demonstrated to be sensitive to inhibition by alpha-fluoromethylhistidine but not by phenylalanine. Although the enzyme shows a half-life of only 3 h in cell-free extract, the initial high recovery of activity allowed for active-site labelling of the enzyme by [3H]histidine and NaBH4. Labelled protein migrated on non denaturing polyacrylamide-gradient-gel electrophoresis as a 55,000 Da species. PMID- 3342013 TI - The switching of electron flux from the cyanide-insensitive oxidase to the cytochrome pathway in mung-bean (Phaseolus aureus L.) mitochondria. AB - The activities of the mung-bean (Phaseolus aureus L.) mitochondrial cyanide insensitive oxidase and cytochrome pathways have been measured simultaneously. The results show that electrons can be diverted both from the alternative pathway to the cytochrome pathway and from the cytochrome to the alternative pathway. The competition of the two pathways for the available electron flux is discussed. PMID- 3342011 TI - L-myo-inositol 1,4,5,6-tetrakisphosphate is present in both mammalian and avian cells. AB - When myo-[3H]inositol-prelabelled primary-cultured murine bone-marrow-derived macrophages were challenged with platelet-activating factor (PAF; 200 ng/ml), there was a rapid (2.5-fold at 10 s) rise in the intracellular concentration of D myo-[3H]inositol 1,4,5-trisphosphate, followed by a rise in myo-[3H]inositol tetrakisphosphate. myo-[3H]Inositol tetrakisphosphate fractions were isolated by high-performance anion-exchange chromatography from myo-[3H]inositol-prelabelled chick erythrocytes and primary-cultured macrophages. In both cases [3H]iditol and [3H]inositol were the only significant products (greater than 90% of recovered radioactivity) after oxidation to completion with periodic acid, reduction with NaBH4 and dephosphorylation with alkaline phosphatase. The presence of [3H]inositol after this procedure is consistent with the occurrence of [3H]inositol 1,3,4,5-tetrakisphosphate in the cell extracts, whereas [3H]iditol could only be derived from D- or L-inositol 1,4,5,6-tetrakisphosphate. When [3H]inositol tetrakisphosphate fractions obtained from (A) unstimulated macrophages, (B) macrophages that had been stimulated with PAF for 40s or (C) chick erythrocytes were subjected to the above procedure, radioactivity was recovered in these polyols in the following proportions: A, 60-90% in iditol, with 10-40% in inositol; B, total radioactivity increased by a factor of 9.8, 94% being recovered in inositol and 8% in iditol; C, 70-80% in iditol and 20-30% in inositol. [3H]Iditol derived from myo-[3H]inositol tetrakisphosphate fractions from macrophages and chick erythrocytes was oxidized to sorbose by L-iditol dehydrogenase (L-iditol:NAD+2-oxidoreductase, 1.1.1.14) at the same rate as authentic L-iditol. D-[14C]Iditol, derived from D-myo-inositol 1,4,5 trisphosphate, was not oxidized by L-iditol dehydrogenase. This result indicates that the [3H]iditol was derived from L-myo-inositol inositol 1,4,5,6 tetrakisphosphate. The data are consistent with rapid PAF-sensitive synthesis of D-myo-[3H]inositol 1,3,4,5-tetrakisphosphate in macrophages, and demonstrate that L-myo-inositol 1,4,5,6-tetrakisphosphate is synthesized in both mammalian and avian cells. The levels of L-myo-[3H]inositol 1,4,5,6-tetrakisphosphate in primary-cultured macrophages are not acutely sensitive to PAF. PMID- 3342014 TI - Increased lipoprotein lipase content in the adipose tissue of suckling and weaning obese Zucker rats. AB - The aim of this study was to determine whether the increase in lipoprotein lipase activity displayed by the adipose tissue of obese (fa/fa) rats as compared with that of lean (Fa/fa) rats could be ascribed to a change in the content or in the catalytic properties of the enzyme. The question was addressed in rats of two ages: in 7-day-old suckling and in 30-day-old post-weaning pups. Inguinal fat pads were removed surgically (7 days of age) or after killing (30 days of age), and acetone-extract powders were prepared. The relative quantity of enzyme was assessed by immunotitration using an antiserum raised in goat against purified lipoprotein lipase from rat adipose tissue. The results indicate that increases in enzyme activity in obese animals were strictly paralleled by increases in the amount of enzyme in suckling as well as in post-weaning pups. Moreover, the apparent Km values of lipoprotein lipase for its substrate triacylglycerol were identical in the two genotypes. In conclusion, the genotype-mediated increase in lipoprotein lipase activity in adipose tissue of obese Zucker rats was fully accounted for by an increase in the content of the enzyme. In addition, this work documents the mechanism of the increase in lipoprotein lipase activity during weaning, which is mediated mainly through changes in the adipose-tissue enzyme content. PMID- 3342015 TI - Brain energy metabolism in streptozotocin-diabetes. AB - Regional brain glucose use was measured in rats with streptozotocin-induced diabetes (65 mg/kg intravenously) of 1 or 4 weeks duration, by using [6 14C]glucose and quantitative autoradiography. The concentrations of several metabolites were measured in plasma and brain. Results were compared with those from normal untreated rats. Glucose concentrations were increased in both plasma and brain, to similar degrees in both diabetic groups. Plasma ketone-body concentrations were 0.25, 1.0, and 3.15 mumol/ml in the control, 1-week and 4 week groups respectively (sum of acetoacetate and 3-hydroxybutyrate). Glucose use was increased throughout the brain (differences were statistically significant in 55 of 59 brain areas) after 1 week of diabetes, with an increase of 25% for the brain as a whole. In contrast, normal rates were found throughout the brain after 4 weeks of diabetes. None of the brain areas was affected significantly differently from the others, in either diabetic group. There was no significant loss of 14C as lactate or pyruvate during the experimental period, nor was there any indication of net production of lactate in any of the groups. Other methodological considerations that could have affected the results obtained in the diabetic rats were likewise ruled out. Because the ketone bodies are expected to supplement glucose as a metabolic fuel for the brain, our results indicate that brain energy consumption is increased during streptozotocin-diabetes. PMID- 3342016 TI - Detection of short-chain carbonyl products of lipid peroxidation from malaria parasite (Plasmodium vinckei)-infected red blood cells exposed to oxidative stress. AB - Reversed-phase h.p.l.c. was used to detect 2,4-dinitrophenylhydrazine-reactive carbonyl products, which excludes malonaldehyde, in malaria-parasite (Plasmodium vinckei)-infected murine red blood cells (RBCs). A number of alkanals, 4 hydroxyalk-2-enals and alka-2,4-dienals were tentatively identified by comparison with authentic standards. The formation of 4-hydroxynon-2-enal, deca-2,4-dienal and hexanal was greater in P. vinckei-infected RBCs than in their uninfected counterparts and was increased by the presence of t-butyl hydroperoxide. Several of these aldehydes have previously been shown to be toxic to various types of cells, including P. falciparum, in vitro. The iron chelator desferrioxamine and the free-radical scavenger butylated hydroxyanisole inhibited the formation of these aldehydes. These experiments demonstrate that products of lipid peroxidation other than malonaldehyde are formed during the exposure of malaria infected RBCs in vitro to drugs that generate reactive oxygen species and have anti-parasitic activity. The formation of products of this type during the natural course of malaria infection may have implications for the mechanisms underlying intra-RBC parasite death and the tissue damage associated with the disease. PMID- 3342017 TI - Zinc and copper accumulation and isometallothionein induction in mouse ascites sarcoma S180A cells. AB - To investigate Zn and Cu accumulation and isometallothionein (iso-MT) induction in ascites-sarcoma S180A cells, 5 micrograms of Zn2+ or Cu2+/g body weight was administered to tumour-bearing mice intraperitoneally. In the tumour cells the Zn or Cu concentration increased more than in the host liver, which is the target organ for those metals; the maximum Zn or Cu level was about 2-3 times that in the host liver. The amounts of Zn-MT or Cu-MT accumulated in the tumour cells and host liver were proportional to such dose accumulation levels in the each cytosol; the maximum level of Zn-MT or Cu-MT was 4 or 2 times higher than in the host liver. MT accumulated in the tumour cells showed two subfractions (MT-1 and MT-2); the ratio of Zn (or Cu) bound to MT-1 to that bound to MT-2 in the host liver and tumour cells was 1.0 (or 1.0) and 0.7 (or 0.25) respectively, suggesting that the induction level of MT-2 in the tumour cells is more than that of MT-1. The h.p.l.c. profiles (using an anion-exchange column) of the isolated MT-1 and MT-2 subfractions from Zn-treated normal-mouse liver showed a single peak (MT-1-1) and two peaks (MT-2-1 and MT-2-2) respectively; mouse MTs were separated into three isoforms. In the ascites cells, the MT fraction obtained by a gel filtration was also separated into three isoforms; however, the amount of MT-2-1 isoform was 3 times that in the Zn-treated normal-mouse liver. PMID- 3342018 TI - The mechanism of action of GTP on Ca2+ efflux from rat liver microsomal vesicles. Measurement of vesicle fusion by fluorescence energy transfer. AB - 1. GTP-promoted fusion between microsomal vesicles was studied by using fluorescence-resonance-energy transfer between the fluorescent membrane probes octadecanoyl-aminofluorescein and octadecyl-rhodamine. 2. The fluorescence increase after GTP addition does not require the presence of ATP, is unaffected by changes in free [Ca2+] in the range 10 microM-1 nM, but requires Mg2+, although higher Mg2+ concentrations are inhibitory. 3. In terms of requirements for poly(ethylene glycol), dependence on GTP concentration and inhibition by high Mg2+ concentrations, there is excellent correlation between rate of increase in fluorescence and rate of GTP-promoted Ca2+ efflux measured under Ca2+ transport conditions. 4. The observations support our previous conclusions that GTP-induced membrane fusion plays a major role in causing GTP-promoted Ca2+ efflux from microsomal vesicles. PMID- 3342019 TI - Delta 6-desaturase activity in liver microsomes of rats fed diets enriched with cholesterol and/or omega 3 fatty acids. AB - The effect of feeding semipurified diets enriched in linseed (rich in C18:3, omega 3 fatty acid) or fish (rich in C20:5, omega 3 and C22:6, omega 3 fatty acid) oil with and without cholesterol supplementation on the desaturation of linoleic acid (C18:2, omega 6) by rat liver microsomal fractions was investigated. Animals fed diets supplemented with beef tallow were used as equal energy controls. Both linseed-oil and fish-oil diets, without added cholesterol, decrease conversion of C18:2, omega 6 fatty acid to gamma-linolenic acid (C18:3, omega 6). Reduction in delta 6-desaturation was significantly greater for animals fed the diet containing fish oil than with animals fed the linseed-oil diet. The major effect of cholesterol supplementation was to decrease the rate of desaturation of C18:2, omega 6, when fed in combination with the beef-tallow diet, whereas delta 6-desaturation was unaffected when cholesterol was fed along with diets high in omega 3 fatty acids (linseed oil or fish oil). The activity of the delta 6-desaturase in vitro is consistent with the fatty acid composition observed for the microsomal membranes on which this enzyme is localized. Dietary linseed oil and fish oil lowered the arachidonic (C20:4, omega 6) acid content of rat liver microsomes, with an accompanying increase in membrane eicosapentaenoic (C20:5, omega 3) and docosahexaenoic (C22:6, omega 3) acid content, in comparison with the group fed beef tallow. Inclusion of cholesterol into the beef-tallow or linseed-oil diets resulted in decreased membrane C20:4, omega 6-fatty-acid content, with concomitant increase in C18:2, omega 6-fatty-acid content. However, addition of cholesterol to the fish-oil diet did not alter the microsomal membrane content of C20:4, omega 6 fatty acid. Thus it is suggested that (1) the decrease in prostaglandin E2, thromboxane and prostacyclin levels generally observed after fish-oil consumption may be at least partly due to inhibition of C20:4, omega 6-fatty-acid synthesis from C18:2, omega 6 fatty acid; and (2) consumption of fish oil prevents the further decrease in C20:4, omega 6-fatty acid levels by dietary cholesterol that is apparent when cholesterol is fed in combination with diets high in saturated fat or C18:3, omega 3 fatty acid. PMID- 3342020 TI - Inhibition by nucleosides of glucose-transport activity in human erythrocytes. AB - The interaction of nucleosides with the glucose carrier of human erythrocytes was examined by studying the effect of nucleosides on reversible cytochalasin B binding activity and glucose transport. Adenosine, inosine and thymidine were more potent inhibitors of cytochalasin B binding to human erythrocyte membranes than was D-glucose [IC50 (concentration causing 50% inhibition) values of 10, 24, 28 and 38 mM respectively]. Moreover, low concentrations of thymidine and adenosine inhibited D-glucose-sensitive cytochalasin B binding in an apparently competitive manner. Thymidine, a nucleoside not metabolized by human erythrocytes, inhibited glucose influx by intact cells with an IC50 value of 9 mM when preincubated with the erythrocytes. In contrast, thymidine was an order of magnitude less potent as an inhibitor of glucose influx when added simultaneously with the radioactive glucose. Consistent with this finding was the demonstration that glucose influx by inside-out vesicles prepared from human erythrocytes was more susceptible to thymidine inhibition than glucose influx by right-side-out vesicles. These data, together with previous suggestions that cytochalasin B binds to the glucose carrier at the inner face of the membrane, indicate that nucleosides are capable of inhibiting glucose-transport activity by interacting at the cytoplasmic surface of the glucose transporter. Nucleosides may also exhibit a low-affinity interaction at the extracellular face of the glucose transporter. PMID- 3342021 TI - Induction of hepatic metallothioneins determined at isoprotein and messenger RNA levels in glucocorticoid-treated rats. AB - Induction of metallothionein-I (MT-I) and metallothionein-II (MT-II) by glucocorticoids was determined by h.p.l.c. analysis of proteins and Northern-blot analysis of MT mRNAs. Rats were injected with dexamethasone (0.03-10 mumol/kg) and hepatic concentrations of MTs were determined 24 h later. In control rats, only MT-II was detected (9.4 +/- 2.5 micrograms/g of liver), whereas the hepatic concentration of MT-I was below the detection limit (5 micrograms of MT/g). Dexamethasone did not increase MT-I above the detection limit at any dosage tested, but MT-II increased to 2.5 times control values at dosages of 0.30 mumol/kg and higher. Time-course experiments indicated that MT-II reached a maximum at 24 h after a single dosage of dexamethasone and returned to control values by 48 h. To determine whether dexamethasone increased MT-I in liver, samples were saturated with 109Cd, after which the amount of 109Cd in MT-I and MT II was determined. Results indicated that, by this approach, MT-I and MT-II could be detected in control rats, and there was approx. 1.8 times more 109Cd in MT-II than in MT-I. At 24 h after administration of dexamethasone (1 mumol/kg), there was a small increase in the amount of 109Cd bound to MT-I, whereas the amount of 109Cd bound to MT-II increased to more than 2 times control values. Northern-blot hybridization with mouse cRNA probes indicated that MT-I and MT-II mRNAs increased co-ordinately after administration of dexamethasone. Thus, although glucocorticoids increase both MT-I and MT-II mRNAs, MT-II preferentially accumulates after administration of dexamethasone. PMID- 3342022 TI - Amino acid metabolism in tumour-bearing mice. AB - Mice bearing the Lewis lung carcinoma showed a high tumour glutaminase activity and significantly higher concentrations of most amino acids than in both the liver and the skeletal muscle of the host. Tumour tissue slices showed a marked preference for glutamine, especially for oxidation of its skeleton to CO2. It is proposed that the metabolism of this particular carcinoma is focused on amino acid degradation, glutamine being its preferred substrate. PMID- 3342023 TI - Regulation of GDP binding and uncoupling-protein concentration in brown-adipose tissue mitochondria. The effects of cold-acclimation, warm-reacclimation and noradrenaline. AB - We have used a specific immunoassay for uncoupling protein and [3H]GDP binding to study the acute and chronic responses of brown-adipose-tissue (BAT) mitochondria of warm-acclimated rats to housing at 4 degrees C and cold-acclimated rats to housing at 27 degrees C. These studies have shown the following. (1) In the cold exposed rat the increase in mitochondrial uncoupling-protein concentration parallels the increase in GDP binding from 1 day to 5 days, but that acutely (initial 4 h) the increase in GDP binding is not associated with any change in uncoupling-protein concentration. 2. In the cold-acclimated rat rehoused at 27 degrees C, GDP binding fell by over 50% in the first 2 days, without any change in uncoupling-protein concentrations. 3. Noradrenaline acutely (30 min) increased BAT mitochondrial GDP binding of lean and obese Zucker rats, without any change in uncoupling-protein concentrations. 4. The increases in GDP binding in cold exposed rats were associated with increases in the rate of swelling of mitochondria in the presence of valinomycin and potassium acetate. The evidence supports the hypothesis that the acute response of the rat to changes in environmental temperature are associated with unmasking or remasking of uncoupling protein, whereas chronically changes in uncoupling-protein concentration predominate. PMID- 3342024 TI - Pseudouridine distribution in mammalian 18 S ribosomal RNA. A major cluster in the central region of the molecule. AB - Human and rodent 18 S rRNA contain about 38 pseudouridine residues. By correlating RNA oligonucleotide data with complete sequence data derived from ribosomal DNA, 30 pseudouridine residues can be located in the RNA sequence, either exactly or to within two or three residues. Pseudouridine and 2'-O-methyl groups are interspersed throughout mammalian 18 S rRNA, but not in closely parallel fashion. Whereas the largest cluster of 2'-O-methyl groups is in the 5' one-third of the molecule, the greatest concentration of pseudouridine is in the central one-third of the molecule. PMID- 3342025 TI - The complete sequence of a frog alpha-tubulin gene and its regulated expression in mouse L-cells. AB - A frog alpha-tubulin cDNA and a frog alpha-tubulin gene, closely related to the cDNA, were cloned and sequenced and the structure of the gene deduced. The gene was introduced into mouse L-cells in order to investigate the transcription and regulation of the gene. The gene was transcribed and there was processing of the transcripts. Furthermore, the gene displayed the correct autoregulatory feedback control. PMID- 3342027 TI - Homogeneity of [3H]ouabain-binding sites in rat soleus muscle. AB - Homogeneity or heterogeneity of rat soleus-muscle Na,K-ATPase (Na+ + K+-dependent ATPase) with respect to affinity for [3H]ouabain was evaluated. Since the standard method for measuring specific [3H]ouabain binding to rat skeletal-muscle samples includes subtraction of a value for non-specific [3H]ouabain uptake and retention, and a wash-out in the cold to remove [3H]ouabain from the extracellular phase, it was possible that these procedures could hide a class of [3H]ouabain-binding sites either with low affinity or with a rapid dissociation of [3H]ouabain. However, measurements of [3H]ouabain uptake and retention over the range 0.1-5 mM, as well as the omission of wash-out, gave no evidence for heterogeneity of [3H]ouabain-binding sites in rat soleus muscle. Furthermore, the observation of agreement between the uptake and retention of non-specific [3H]ouabain and of [14C]sucrose gave no evidence for the existence of a major pool of [3H]ouabain-binding sites with low affinity for [3H]ouabain. Assuming homogeneity, the total concentration of [3H]ouabain binding sites in soleus muscle samples from 12-week-old rats is 278-359 pmol/g wet wt. PMID- 3342026 TI - Haem synthesis during cytochrome P-450 induction in higher plants. 5 Aminolaevulinic acid synthesis through a five-carbon pathway in Helianthus tuberosus tuber tissues aged in the dark. AB - Chlorophyll and haem synthesis in illuminated Jerusalem artichoke tuber tissues were very efficiently inhibited by gabaculine (3-amino-2,3-dihydrobenzoic acid). This inhibition seems to be due specifically to a blockade of the pathway for 5 aminolaevulinate biosynthesis which used glutamate as a substrate (the so-called C5 pathway) since we could not detect any inhibition of protein synthesis in the treated tissues and there was no effect of gabaculine on the glycine-dependent yeast 5-aminolaevulinate synthase used as a model. In dark-aged artichoke tissues, gabaculine also effectively blocked cytochrome P-450 induction, peroxidase activity and 5-aminolaevulinic acid synthesis, thus suggesting the involvement of a C5 pathway in cytoplasmic and microsomal haemoprotein synthesis in this higher plant. Allylglycine and (2-amino-ethyloxyvinyl)glycine, two olefinic glycine analogues which are potential suicide inhibitors of pyridoxal phosphate enzymes, were also demonstrated to be effective blockers of chlorophyll synthesis in artichoke tuber and Euglena cells exposed to light. PMID- 3342028 TI - Nucleoside transport in rat cerebral-cortical synaptosomes. Evidence for two types of nucleoside transporters. AB - The transport of [U-14C]uridine was investigated in rat cerebral-cortical synaptosomes using an inhibitor-stop filtration method. Under these conditions the rapid efflux of uridine from the synaptosomes is prevented and uridine is not significantly metabolized in the synaptosome during the first 1 min of uptake. The dose-response curve for the inhibition of uridine transport by nitrobenzylthioinosine (NBMPR) was biphasic: approx. 40% of the transport activity was inhibited with an IC50 (concentration causing half-maximal inhibition) value of 0.5 nM, but the remaining activity was insensitive to concentrations as high as 1 microM. Similar biphasic dose-response curves were observed for dilazep inhibition, but both transport components were equally sensitive to dipyridamole inhibition. Uridine influx by both components was saturable (Km 300 +/- 51 and 214 +/- 23 microM, and Vmax. 12 +/- 3 and 16 +/- 3 pmol/s per mg of protein, for NBMPR-sensitive and NBMPR-insensitive components respectively), and inhibited by other nucleosides such as 2-chloroadenosine, adenosine, inosine, thymidine and guanosine with similar IC50 values for the two components. Inhibition of uridine transport by NBMPR was associated with high affinity binding of NBMPR to the synaptosome membrane (Kd 58 +/- 15 pM). Binding of NBMPR to these sites was competitively blocked by uridine and adenosine and inhibited by dilazep and dipyridamole, with Ki values similar to those measured for inhibiting NBMPR-sensitive uridine influx. These results demonstrate that there are two components of nucleoside transport in our rat synaptosomal preparation that differ in their sensitivity to inhibition by NBMPR. Thus conclusions regarding nucleoside transport in rat brain based only on NBMPR binding activity must be viewed with caution. PMID- 3342029 TI - Formaldehyde adducts of glutathione. Structure elucidation by two-dimensional n.m.r. spectroscopy and fast-atom-bombardment tandem mass spectrometry. AB - Aqueous mixtures of formaldehyde and glutathione react to form a variety of cyclized adducts in addition to S-hydroxymethylglutathione. The adducts are in labile equilibrium with each other and are not readily separated. The structures of two of the other major adducts were determined by concerted application of 13C 1H two-dimensional chemical-shift correlation, fast-atom-bombardment mass spectrometry and tandem mass spectrometry to the adduct mixtures in aqueous solution. PMID- 3342032 TI - The possible contribution of glucose autoxidation to protein modification of diabetes. PMID- 3342033 TI - Aldehydes and dicarbonyls in non-enzymic glycosylation of proteins. PMID- 3342031 TI - Cloning of cDNA to rat mammary-gland fatty acid synthase mRNA. Evidence for the expression of two mRNA species during lactation. AB - A cDNA library was constructed in the expression vector lambda gt11, by synthesizing cDNA from size-selected poly(A) RNA from lactating rat mammary gland, using random hexanucleotide primers. Using this library we identified two recombinants which, on addition of a lac z inducer, produced proteins recognized by affinity-purified anti-fatty-acid synthase antibody, and which, therefore, contained fatty acid synthase coding sequences. The inserts were subcloned, were shown to be between 500 and 600 base pairs in size, and to cross-hybridize. The cloned DNA was then used in Northern hybridizations with mRNA isolated at various stages throughout lactation. Two mRNA species were identified of approx. 9.7 and 10.4 kilobases, which increased and decreased in parallel during lactation, reaching a peak at 12-13 days. Both mRNA species disappeared rapidly if the pups were removed prematurely. This study provides evidence that, during hormonal induction in lactation, regulation of the level of fatty acid synthase protein can be accounted for by variation in the level of mRNA. PMID- 3342030 TI - Modulation of polyamine-biosynthetic activity by S-adenosylmethionine depletion. AB - The methionine-analogue inhibitor of S-adenosylmethionine (AdoMet) synthetase, L 2-amino-4-methoxy-cis-but-3-enoic acid (L-cisAMB), was used to study the early effects of AdoMet depletion on polyamine biosynthesis. In the presence of decreased methionine (30 microM) in the medium, treatment of cultured L1210 cells with 1 mM-L-cisAMB resulted in a near-total (95%) depletion of cellular AdoMet pools by 4 h. This was accompanied by a 3-fold increase in ornithine decarboxylase (ODC) activity, a 2.5-fold increase in AdoMet decarboxylase (AdoMetDC) activity and a 20% decrease in spermidine and spermine pools. The increase in enzyme activities seemed to be partially due to prolongation of enzyme activity half-life, since that of ODC was extended from 30 to 50 min and that of AdoMetDC from 65 to 310 min. By temporal sequence characterization (0-4 h), the onset of elevations of enzyme activity (0.5-1 h) seemed to be causally related to an earlier (0-0.5 h) decline in AdoMet pools, as opposed to the 20% decrease in spermidine and spermine pools, which occurred much later (2-4 h); the latter are known to regulate decarboxylase activities negatively. Drug-induced elevations in ODC and, to a lesser extent, AdoMetDC activities were reversed by later treatment with exogenous AdoMet. However, because the latter also increased spermine pools (which could not be prevented with various enzyme inhibitors), the reversal of elevations in enzyme activities could not be directly linked to AdoMet. Although not definitive, the data raise the interesting possibility that, in addition to being negatively regulated by polyamines, ODC and AdoMetDC activities may also be subject to negative control by cellular AdoMet (or an AdoMet metabolite). The net effect of either or both of these influences would be to conserve polyamine-biosynthetic activity in the face of declining AdoMet supplies. PMID- 3342034 TI - Novel feature of expression of the sarcotoxin IA gene in development of Sarcophaga peregrina. AB - The expressions of the sarcotoxin IA and IIA genes were investigated. Although both these antibacterial proteins were synthesized by the fat body and secreted into the hemolymph in the same way when the body wall of third instar larvae of Sarcophaga peregrina was injured, the expressions of their genes during development of this insect were different. The sarcotoxin IA gene was activated transiently in the embryonic and pupal stages, whereas the sarcotoxin IIA gene was totally inactive in these stages. These results suggest that sarcotoxin IA plays a role in the development as well as the defence mechanism of Sarcophaga. PMID- 3342035 TI - The weak immunosuppressant cyclosporine D as well as the immunologically inactive cyclosporine H are potent inhibitors in vivo of phorbol ester TPA-induced biological effects in mouse skin and of Ca2+/calmodulin dependent EF-2 phosphorylation in vitro. AB - Various biological effects induced by the tumor promoting phorbol ester TPA in mouse skin are comparably suppressed by the immunologically inactive cyclosporine H (CsH) and by the strongly immunosuppressive cyclosporine A (CsA). These effects inhibited include the development of edema, stimulation of alkaline phosphatase activity, DNA and protein synthesis, as well as tumor promotion. Furthermore, CsH, like CsA, inhibits the Ca2+/calmodulin-dependent phosphorylation of the elongation factor 2 (EF-2) in vitro and the TPA-induced increases in the amount of EF-2 in vivo. Similar observations were made using the weak immunosuppressant CsD. We conclude from these results that the ability of cyclosporines to act as immunosuppressants and their ability to inhibit TPA-effects are based on two different mechanisms of action. Inhibition of TPA-effects may involve suppression of calmodulin-dependent processes, such as augmentation and phosphorylation of EF 2. PMID- 3342036 TI - A two dimensional 1H NMR study of the solution conformation of gastrin releasing peptide. AB - An almost complete assignment of the 1H NMR spectrum of gastrin releasing peptide in dimethyl sulphoxide solution and aqueous solution has been carried out using two dimensional NMR techniques. The chemical shifts in both solvents have been compared with the corresponding values in random coil polypeptides and it is concluded that gastrin releasing peptide adopts little short or long range order under either solvation conditions. PMID- 3342037 TI - Hypoxic damage generates reactive oxygen species in isolated perfused rat liver. AB - The aim of the present study was to investigate the possible role of reactive oxygen species in the pathogenesis of hypoxic damage in isolated perfused rat liver. One hour of hypoxia caused severe cell damage (lactate dehydrogenase release of greater than 12,000 mU/min/g liver wt) and total irreversible cholestasis which was accompanied by a loss of cellular ATP and a marked decrease in lactate efflux. Tissue glutathione disulfide (GSSG) content and GSSG efflux as a measure of hepatic reactive oxygen formation was less than 1% of total glutathione before and during hypoxia. Upon reoxygenation, however, hepatic GSSG content increased sharply to about twice the control values and GSSG efflux increased several-fold to around 3-4 nmol GSH-equivalents/min/g. The release of lactate dehydrogenase decreased upon reoxygenation and tissue ATP content recovered partially. When livers were reoxygenated at an earlier time interval than 1 hr of hypoxia, i.e., before the onset of damage, no enhanced GSSG formation was observed. The results demonstrate that hypoxic damage is a prerequisite to reactive oxygen formation during the subsequent reoxygenation period. Thus, reactive oxygen species appear unlikely to play a crucial role in the pathogenesis of hypoxic liver damage in the hemoglobin-free, isolated perfused liver model. PMID- 3342038 TI - Transforming growth factor beta activates protein kinase C in microvessels isolated from immature rat brain. AB - We investigated the activation of protein kinase C in microvessels isolated from rat brain. We found that unstimulated kinase activity in microvessels from immature animals is soluble while that from adults is particulate. The tumor promoter, phorbol 12-myristate 13-acetate, and the diacylglycerol analog, 1 oleoyl-2-acetyl-sn-glycerol, caused the redistribution of protein kinase C activity to the membrane fraction in microvessels from immature rats. Exposure to transforming growth factor beta resulted in similar redistribution of kinase activity. To our knowledge, this is the first report of an effect of transforming growth factor beta on protein kinase C. The kinase activity in microvessels from adult animals was unaffected by exposure to these agonists. We suggest that protein kinase C activation promotes differentiation of the brain microvasculature. Transforming growth factor beta may mediate this process. PMID- 3342039 TI - Chromosome 5 allele loss at the glucocorticoid receptor locus in human colorectal carcinomas. AB - Matched normal/tumor DNA pairs from sporadic colon carcinoma patients were examined for chromosome 5 allele loss using a probe for a functional gene (glucocorticoid receptor = GRL) locus. This locus maps (5q11-q13) close to one of two alternative sites recently reported for a constitutional deletion in a familial adenomatous polyposis (FAP) patient. Tumor-specific allele loss of at least 27% at GRL supports the hypothesis that both hereditary and sporadic forms of colon cancer result from mutations of the same gene. The proximity of the GRL locus to the region of 5q affected in FAP and the observed tumor-specific allele loss at this locus suggest that further research is needed regarding whether genetic alterations in the glucocorticoid receptor may be associated with colon carcinogenesis. PMID- 3342040 TI - Heterogeneity of immunoreactive prolactin in the rat brain. AB - Three immunoreactive prolactin proteins (24 Kd, 16 Kd, and 12 Kd) were identified in the rat brain using sodium dodecyl sulphate polyacrylamide gel electrophoresis, and western blot analyses. In male and female brains, the primary prolactin protein has a molecular weight of 24 Kd which is similar to that of pituitary prolactin. Two additional proteins with apparent molecular weights of 16 Kd and 12 Kd were also identified and were found in greater concentrations in the brain than in the pituitary, and were more predominant in the female brain. In addition, brain extracts proteolytically modify the 24K dalton PRL resulting in the formation of two fragments with apparent molecular weights of 16 and 8 Kd. These data indicate that the prolactin identified in the rat brain is similar to pituitary prolactin, and suggests, that like other PRL target tissues the brain may have the capacity to proteolytically modify prolactin. PMID- 3342041 TI - DL-myo-inositol 1,4,5-trisphosphorothioate mobilizes intracellular calcium in Swiss 3T3 cells and Xenopus oocytes. AB - The initial water-soluble product of receptor-stimulate polyphosphoinositide hydrolysis, D-myo-inositol 1,4,5-trisphosphate is now accepted as the second messenger that stimulates release of Ca2+ from intracellular pools. We report here the first examples of Ca2+ release by a novel phosphatase-resistant inositol trisphosphate analogue, DL-myo-inositol 1,4,5-trisphosphorothioate, in Swiss 3T3 cells and Xenopus oocytes. L-myo-inositol 1,4,5-trisphosphate was inactive in the latter system. PMID- 3342042 TI - Sialic acid is selectively involved in the interaction of agonists with M2 muscarinic acetylcholine receptors. AB - Neuraminidase and slight acid hydrolysis were used to investigate the role of sialic acid residues in the binding of muscarinic agonists and antagonists to membranes from tissues rich in M1 and M2 receptors. Membranes were pretreated with neuraminidase at pH 5 and the binding parameters were determined from competitive experiments with (3H)-quinuclidinylbenzylate. The removal of sialic acid residues reduced the affinity of muscarinic agonists for cerebellum, heart and lung membranes (M2), in contrast to striatum (M1). The affinity of antagonists was not affected. Thus, sialic acid is selectively involved in the interaction of agonists with M2 muscarinic receptors. PMID- 3342043 TI - Expression of heme oxygenase gene in rat and human liver. AB - Developmental changes of microsomal heme oxygenase were studied. In human fetal liver, the enzyme activity was 8 times higher than that detected in the adult liver. On the other hand, adult livers contained 4 times more cytochrome P450 than fetal livers. Elevated heme oxygenase activity in fetal liver was not due to modulators present in the microsomes. Similar to human, rat fetal liver also contained high enzyme activity which appeared to be regulated at the transcriptional level. Hybridization analysis of rat liver RNAs with cDNA for rat heme oxygenase revealed that the level of mRNA for the enzyme was 3-fold higher in the fetus than in the adult. The low cytochrome P450 content may be due in part to the high heme oxygenase activity in fetal livers. PMID- 3342045 TI - DNA hypomethylation in ethionine-induced rat preneoplastic hepatocyte nodules. AB - DNA from hepatocyte nodules induced in rats with dietary DL-ethionine and from the surrounding non-nodular liver contained less 5-methyldeoxycytidine per deoxycytidine when compared with that from normal adult liver. The degree of apparent hypomethylation, 37% in nodules and 20% in the surrounding liver, decreased somewhat (29% and 16% respectively) at 2 weeks after terminating the exposure to ethionine. Nodules and surrounding liver, like normal liver, responded to partial hepatectomy with a decrease in the 5-methyldeoxycytidine level at 24 hrs and a return to the level at the time of partial hepatectomy by 38 hrs. These findings indicate the need for careful control of cell proliferation in comparing the levels of a post-replicative DNA modification, methylation, in proliferating and non-proliferating cell populations. These findings also suggest that a portion of the hypomethylation in preneoplastic nodules may be due to a bona fide decrease in the level of cytosine methylation in the parental strand of DNA. This hypomethylation could be one basis for the altered gene expression in hepatocyte nodules, possible precursors for liver cancer. PMID- 3342044 TI - Serum contains a macromolecular effector promoting the synthesis of nerve growth factor (NGF) in L cells. AB - Addition of serum to the culture medium of murine L cells increased both the cellular level of NGF mRNA and the secretion of mature factor. Stimulation of NGF production by the serum was dose-dependent and appeared mediated by some specific factor(s). After gel filtration chromatography of serum, most of the biological activity formed a major peak with an apparent MW of about 160 kDa. This promoting factor was sensitive to heat at neutral pH, but resisted after heating at pH4. An activity inducing NGF synthesis, and displaying a comparable thermal sensitivity was also detected in Cohn fraction IV of human or bovine plasma. PMID- 3342046 TI - Cytochalasin E enhances the protein kinase C-dependent process of secretion. AB - Platelet dense body secretion, monitored as released serotonin, when induced by 20 nM tetradecanoylphorbol acetate was enhanced by 10 microM cytochalasin E even in the absence of external calcium ions and aggregation. Secretion induced by 500 nM A23187 in the presence of 15 microM indomethacin was not changed by cytochalasin but the synergy between A23187 and phorbol ester was enhanced. Therefore, protein kinase C-mediated secretion is not dependent on filipodal development, granule centralization, external calcium ion concentration or aggregation but is enhanced selectively by cytochalasin. Because the synergy between kinase C and A23187 is very rapid, the rate determining step in the slow secretion induced by phorbol ester alone appears to be the step accelerated by a rise in cytosolic Ca2+ concentration. PMID- 3342047 TI - Analysis of cellular expression of gangliosides by gene transfection. I: GD3 expression in myc-transfected and transformed 3Y1 correlates with anchorage independent growth activity. AB - Transfection of c-myc DNA into rat fibroblastic 3Y1 cell line resulted in the neosynthesis of GD3 ganglioside, as has been previously shown to occur after transfection of 3Y1 cells with adeno El (Nakakuma, H., Sanai, Y., Shiroki, K., and Nagai, Y. (1984) J. Biochem. 96, 1471-1480); in both cases, the products are expressed intranuclearly. Moreover, a clear correlation was identified between levels of GD3 expression and colony-forming activity (in soft agar) of myc transformed 3Y1 cells, implying that GD3 plays some specific role in myc-induced transformation of 3Y1 cell line. PMID- 3342048 TI - Analysis of cellular expression of gangliosides by gene transfection. II: Rat 3Y1 cells transformed with several DNAs containing oncogenes (fes, fps, ras & src) invariably express sialosylparagloboside. AB - The transfection of several DNAs, containing oncogenes ras, src, fes or fps, into rat 3Y1 cells invariably induced the neosynthesis of sialosylparagloboside (SPG; IV3 alpha NeuAc nLcOse4Cer), with a concomitant decrease in GM3. All these oncogenes are 'extranuclear' type oncogenes, of which the products are expressed in the cytoplasm or on the cell surface membrane. These results are in striking contrast to those on the transfection of 'intranuclear' type oncogenes (ex., adeno E1) into the same 3Y1 cells, where GD3 neosynthesis was specifically brought about by the transfection. PMID- 3342049 TI - Properties of component X of rat heart pyruvate dehydrogenase complex. AB - Pyruvate dehydrogenase complex was purified from rat heart. A new component(mol.wt; 52,000) was found in the purified complex in addition to well known three component enzymes. This component(referred to as component X) was acetylated with [2-14C] pyruvate in the absence of CoA as well as lipoate acetyltransferase. The anti-lipoate acetyltransferase antibody reacted with component X and lipoate acetyltransferase, suggesting that component X shows homology with lipoate acetyltransferase in protein structure. cDNA for lipoate acetyltransferase was isolated from rat liver cDNA library in lambda gt 11. cDNA for lipoate acetyltransferase recognized two kinds of mRNAs of 3.5 Kb and 2.5 Kb. PMID- 3342050 TI - Pertussis toxin inhibits angiotensin II-mediated phosphatidylinositol breakdown and ADP-ribosylates a 40 Kd protein in cultured smooth muscle cells. AB - Angiotensin II causes an increase of inositol phosphate production in cultured vascular smooth muscle cells from rat aorta. Pretreatment of the cells with pertussis toxin attenuates this effect. Pertussis toxin ADP-ribosylates a protein of about 40 kD in a crude membrane fraction. These data demonstrate the possible involvement of a GTP-binding protein (G-protein) in the angiotensin II-induced activation of phosphoinositidase in vascular smooth muscle cells. PMID- 3342051 TI - Expression of hepatic microsomal cholesterol 7 alpha-hydroxylase activity in lean and obese Zucker rats. AB - The activity of hepatic microsomal cholesterol 7 alpha-hydroxylase was studied in genetically obese and lean Zucker rats. The liver microsomal cholesterol 7 alpha hydroxylase activity in fatty Zucker rats (fa/fa) is about 50% to 70% lower than that of the lean (Fa/-) rats of the same sex, when animals were sacrificed at the middle of the dark cycle. When rats were sacrificed at the middle of the light cycle, cholesterol 7 alpha-hydroxylase activity was the same as in the dark cycle in obese rats of both sexes, but was 65% lower in lean rats. However, cholesterol 7 alpha-hydroxylase activity was stimulated by the treatment with cholestyramine in both obese and lean rats. Our results suggested that the diurnal regulation of cholesterol 7 alpha-hydroxylase activity is lost in obese rats but was present under cholestyramine treatment in the genetically obese strain of rats. PMID- 3342052 TI - Oxygen limitation induces indirectly the synthesis of cytochrome P-450 mRNA in alkane-growing Candida maltosa. AB - Candida maltosa cells grown on hexadecane under oxygen limitation have an up to 6 fold higher cytochrome P-450 content in comparison to cells cultivated at oxygen saturation. We show by mRNA quantification using an in vitro translation system and subsequent specific immunoprecipitation that the cytochrome P-450 induction occurs mainly on the transcriptional level. The signal for induction may be the enhanced intracellular hexadecane concentration owing to a reduced hydroxylation capacity of the cytochrome P-450 at oxygen limitation. PMID- 3342053 TI - Erythromycin and its derivatives with motilin-like biological activities inhibit the specific binding of 125I-motilin to duodenal muscle. AB - Erythromycin, one of the macrolide antibiotics, and its derivatives had been found to mimic actions of exogenous motilin, a gastrointestinal peptide hormone. We found that some of the macrolide compounds inhibited the specific binding of 125I-motilin to rabbit duodenum muscle at 15 C in a dose-dependent fashion. The inhibitory activity of several macrolides examined did not relate to their antibacterial activity but to their motilin-like activity. A 50% inhibition by EM536, a non-antibacterial erythromycin derivative with the highest motilin-like activity, was obtained at 3-40 nM and little higher than that of non-radioactive motilin (5-6 nM) under the present conditions. The results suggest that erythromycin and its derivatives mimic physiological actions of motilin by acting as agonists for a motilin receptor. PMID- 3342054 TI - Identification of a phosphatidylcholine active phospholipase C in human gallbladder bile. AB - This study describes the identification of a phospholipase C activity against phosphatidylcholine in delipidated human gallbladder bile. All biles were obtained from cholesterol gallstone patients and were negative on bacterial culture. The biliary enzyme was inhibited by EDTA and had a pH optimum of between 7-8. All of the 15 gallbladders examined contained significant phospholipase C activity (32.85 +/- 8.37 nmol/h/mg delipidated protein). The finding of a phospholipase C in gallbladder bile of patients with cholesterol gallstones may be one of the factors responsible for or related to the rapid in vitro nucleation seen in these biles. PMID- 3342055 TI - Non-enzymatic inhibitors of coagulation and platelet aggregation from Naja nigricollis venom are cardiotoxins. AB - Four non-enzymatic polypeptides from Naja nigricollis crawshawii venom were recently isolated and shown to inhibit plasma coagulation and platelet aggregation. We have now determined the amino acid compositions, amino terminal sequences and direct lytic activity of these anticoagulants. The results of these studies allow us to identify the anticoagulants as cardiotoxins. The anticoagulant activity of these cardiotoxins is far more potent than that of other cardiotoxins previously reported to have anticoagulant activity. PMID- 3342057 TI - Quantitative aspects of the feeder cell phenomenon: mechanistic implications. AB - It has been proposed that feeder cells function by supplying lymphocytes with the amino acid cysteine (a thiol compound). The results presented here indicate that thiols are the critical element of the feeder cell phenomenon. Specifically, we noted that the rank of thiol production by four different feeder cell lines corresponds to their relative abilities to support a lymphocyte cell line, CTLL 2. In addition, increasing thiol production by the feeder cells with lipopolysaccharide increased their support of CTLL-2 cells and decreasing it with homocysteate decreased support of CTLL-2 cells. However, it was also noted that substantial (up to 79% maximal) support of CTLL-2 growth was provided by feeder cell concentrations which could not produce detectable levels of free thiols. This prompted us to propose an alternative mechanism for the feeder effect which would explain these apparently paradoxical findings. PMID- 3342056 TI - The site of action of six different ribosome-inactivating proteins from plants on eukaryotic ribosomes: the RNA N-glycosidase activity of the proteins. AB - The site of action of six different ribosome-inactivating proteins from plants on eukaryotic ribosomes was studied. Treatment of ribosomes with any one of these proteins caused the 28S rRNA extracted from the inactivated ribosomes to become sensitive to treatment with aniline. A fragment containing about 450 nucleotides was released from the 28S rRNA. Further analysis of the nucleotide sequences of the 450-nucleotide fragments revealed that the aniline-sensitive phosphodiester bond was between A-4324 and G-4325 of the 28S rRNA. These results indicate that all six ribosome-inactivating proteins damage eukaryotic ribosomes by cleaving the N-glycosidic bond at A-4324 of the 28S rRNA of the ribosomes, as does ricin A chain. PMID- 3342058 TI - Developmental and sexual differences of T-kininogen levels in rat plasma and liver. AB - T-kininogen levels in plasma and liver microsomes were measured by radioimmunoassay in female and male rats of various ages. High levels of T kininogen were found in plasma and liver of 1-day to 1-week old male and female rats and their mothers. The levels in newborns gradually decreased along with their development. In mature male rats the levels were as low as 1/5-1/2 of those in mature female rats. Treatment with estradiol increased the plasma and the liver levels of T-kininogen significantly in both sexes, but testosterone decreased the level in female rats and had no effect in male rats. These results suggest that sex hormones may regulate the physiological level of T-kininogen in rats. PMID- 3342059 TI - Feeding of lovastatin to rats increases the activity of the hepatic mitochondrial outer carnitine palmitoyltransferase. AB - Administration of lovastatin to male, Sprague-Dawley rats by addition of the drug to the normal chow diet caused a two-fold increase in the activity of the hepatic mitochondrial outer carnitine palmitoyltransferase, but lovastatin apparently did not affect the sensitivity of the outer carnitine palmitoyltransferase to inhibition by malonyl-CoA. There was also no effect of lovastatin on the activity of the hepatic mitochondrial inner carnitine palmitoyltransferase. Feeding of cholestyramine to rats did not affect either the mitochondrial outer carnitine palmitoyltransferase or the mitochondrial inner carnitine palmitoyltransferase. PMID- 3342061 TI - Distinction between malignant and normal breast tissue based on endogenous mediators of estradiol binding. AB - A component of human breast tumors, isolated by chromatographing the cytosol on hydroxylapatite, increased specific estradiol binding by the cytosolic proteins (23/24) while a similarly isolated component of normal sections of the cancerous breasts inhibited sharply the binding (17/17). Using the same procedures, a component isolated from rat uteri excised at proestrus acted like the one from human breast tumors and a component isolated from uteri at the other phases of the cycle acted like the one from normal breast tissue. The described hormone binding differences are revealed in incubations at 37 degrees C with divalent copper present in the incubation mixture. PMID- 3342060 TI - Sequence of the signal peptide for rat liver mitochondrial aldehyde dehydrogenase. AB - The cDNA coding for the signal peptide of rat liver mitochondrial aldehyde dehydrogenase was sequenced. The deduced amino acid sequence of the signal peptide was MLRAALSTARRGPRLSRLL. From this sequence an amphiphilic helix which had a high hydrophobic moment could be constructed. A comparison to the published cDNA sequence of human mitochondrial aldehyde dehydrogenase revealed great sequence identity and allowed us to make some predictions regarding the primary structure of the human signal peptide. PMID- 3342062 TI - Thiol exchange reactions involving selenotrisulfides. AB - The occurrence of in vitro thiol exchange reactions involving selenotrisulfides has been documented by HPLC analyses of reaction solutions. Asymmetric selenotrisulfide (RSSeSR') (R,R' = penicillamine, cysteine, glutathione) was formed by the reactions between (i) a mixture of thiols and selenite, (ii) thiol (R'SH) and symmetric selenotrisulfide (RSSeSR), and (iii) symmetric selenotrisulfides (RSSeSR and R'SSeSR'). Further reaction of an asymmetric selenotrisulfide with thiol (R'SH) produced another symmetric selenotrisulfide (R'SSeSR'). These thiol exchange reactions may offer significant information to elucidate intake and metabolism of selenium in vivo. PMID- 3342063 TI - Giant polypeptides of skeletal muscle titin: sedimentation equilibrium in guanidine hydrochloride. AB - Titin has been purified from rabbit skeletal myofibrils in guanidine hydrochloride by gel filtration on Sephacryl S-1000. The sedimentation coefficients of denatured titin in 6 M guanidine hydrochloride are highly concentration dependent and follow the equation: 1/S = 0.241 + 0.302 A280. Equilibrium sedimentation studies indicate that the average molecular weight of titin polypeptides is 2.4 to 2.6 X 10(6). PMID- 3342064 TI - Rearrangement of nuclear calmodulin during proliferative liver cell activation. AB - Calmodulin increases about three-fold in rat liver nuclei after partial hepatectomy. The increase is maximal after 24 hours, when DNA synthesis is also maximal. During the same time re-distribution of calmodulin within the nuclear structure takes place, leading to its association with the nuclear matrix. Incubation of normal rat liver nuclei with Ca2+ induces association of calmodulin with the matrix, indicating that the re-distribution of calmodulin during the replicative period is related to the increase in nuclear Ca2+. The nuclear matrix contains several calmodulin binding proteins of which one, having Mr of 130 kDa, has been identified as myosin light chain kinase (MLCK). Three acceptor proteins, having Mr of 120, 65, and 60 kDa decrease 24 hours after partial hepatectomy, MLCK and a protein of Mr 150 kDa instead increase. PMID- 3342065 TI - 1,25-Dihydroxyvitamin D stimulates sodium-dependent phosphate transport by renal outer cortical brush-border membrane vesicles by directly affecting membrane fluidity. AB - We examined the effects of several forms of vitamin D added to renal brush-border membrane suspensions on phosphate and glucose transport and on membrane fluidity. The 1,25-D stimulated and the other vitamin D decreased phosphate uptake. In contrast, glucose uptake was not affected by the treatment of vitamin D. The 1,25 D resulted in a significant shift of the lower transition temperature in Arrhenius plots for phosphate, but not for glucose uptakes, from 15 degrees C to 11.5 degrees C. These data indicate that the 1,25-D may alter membrane fluidity, limited to the phosphate transporter, thus affecting the phosphate uptake. PMID- 3342066 TI - Identification of T-kinin-Leu(T-kinin-containing peptide) released from T kininogen by cathepsin D of granulomatous tissues in rats. AB - Acid proteinases of granulomatous tissues in rats with carrageenin-induced inflammation released kinin from T-kininogen. By column chromatography on pepstatin-Sepharose 4B, two types of acid proteinase seems to be responsible for kinin release. One of the acid proteinase was identified as cathepsin D from SDS polyacrylamide gel electrophoresis and Western-blot analysis, using anti-rat liver cathepsin D IgG. Cathepsin D alone could not release T-kinin, but T-kinin containing peptides. The T-kinin-containing peptides were separated into two peptides by reverse-phase high-performance liquid chromatography. From determination of its amino acid composition and its immunoreactivity toward anti bradykinin antiserum, one of the T-kinin-containing peptides was identified as T kinin-Leu. PMID- 3342067 TI - RU 486 stabilizes a high molecular weight form of the glucocorticoid receptor containing the 90K non-steroid binding protein in intact thymus cells. AB - The interaction with the glucocorticoid receptor of RU 486, a recently described antiglucocorticoid, was investigated in intact cells. When incubated at 37 degrees C with intact rat thymocytes [3H] RU 486 underwent negligible nuclear transfer. Moreover when assayed in physiological buffers, i.e. physiological ionic strength and absence of molybdate, the cytosolic [3H] RU 486-receptor complexes obtained displayed a 7-8 nm Stokes radius after analysis by high performance size exclusion chromatography (HPSEC). These high size complexes appeared stable in the native cytosol but dissociated during sucrose gradient centrifugation. Western blot analysis of the fractions obtained after HPSEC separation was performed using a monoclonal antibody able to recognize the 90K non steroid binding protein associated with the molybdate stabilized glucocorticoid receptor complexes. This antibody clearly demonstrated the presence of a 90K non-steroid binding protein in the 7-8 nm peak obtained with [3H] RU 486 receptor complexes. On the contrary [3H] triamcinolone acetonide in the same conditions yielded a 5 nm peak of transformed receptor which did not contain the 90K protein. Thus RU 486, in absence of molybdate, stabilized the 90K protein-receptor interaction in intact cells, an event probably related to its antiglucocorticoid activity. PMID- 3342069 TI - Perturbation of intracellular pH by DIDS on endocytosis of transferrin and iron uptake in rabbit reticulocytes. AB - DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) inhibited transferrin and iron uptake by rabbit reticulocytes in a dose-dependent manner. Measurement of intracellular pH shows that DIDS neutralized the pH in the intracellular vesicles and at the same time, rendered the cytoplasmic pH more acidic. The latter may be the result of a perturbance in the acid-extruding mechanism(s) by DIDS, a known anion exchange blocker. Examination of the single-cycle endocytosis of transferrin with pulse-chased technique suggests that DIDS retarded transferrin internalization, iron unloading and transferrin receptor recycling in the cells. PMID- 3342068 TI - Effect of synthetic human cholecystokinin-33 on exocrine pancreas. AB - Synthetic human cholecystokinin-33 was first evaluated with respect to the biological activity on the pancreatic protein secretion. Human cholecystokinin-33 increased pancreatic protein secretion in a dose-related manner. The relative molar potency of this substance compared to that of synthetic cholecystokinin-8 (taken as 1.0) was 0.92. This study supports the concept that longer molecular forms of cholecystokinin are quantitatively important mediators of biological action of cholecystokinin on the pancreas. PMID- 3342070 TI - Alzheimer's disease brain extract stimulates the survival of cerebral cortical neurons from neonatal rats. AB - Cell cultures of neonatal rat cerebral cortex in a serum-free medium were used to investigate a lack of neuronotrophic factors in Alzheimer's disease (AD) brain. A few neurons survived in the absence of brain extract. The addition of normal brain extract resulted in a 2.5-fold increase in neuronal survival. AD brain extract contained 4-fold neuronotrophic activity of normal brain extract. These findings are in contrary to the previous hypothesis of a lacking neuronotrophic factors in AD brain. These new results may change the concept of mechanism of neuronal death in AD. PMID- 3342072 TI - Mechanism of inactivation of gamma-aminobutyric acid aminotransferase by (S,E)-4 amino-5-fluoropent-2-enoic acid. AB - Evidence for an enamine mechanism of inactivation of pig brain gamma-aminobutyric acid (GABA) aminotransferase by (S,E)-4-amino-5-fluoropent-2-enoic acid is presented. apo-GABA aminotransferase reconstituted with [3H]pyridoxal 5' phosphate is inactivated by (S,E)-4-amino-5-fluoropent-2-enoic acid and the pH is raised to 12. All of the radioactivity is released from the enzyme as an adduct of the cofactor; no [3H]pyridoxamine 5'-phosphate is generated. PMID- 3342071 TI - Determination of mechanisms of myocardial ischemic injury by 31P-MRS effect of catecholamine on ischemic hearts. AB - To investigate mechanisms of development in ischemic myocardial injury, intracellular pH and high energy phosphates in perfused guinea-pig hearts were monitored by 31P-MRS. Intracellular ATP content decreased to 1.2% and 26.4% of control during 60 minutes global ischemia, respectively with and without preischemic administration of isoproterenol. Intracellular pH declined to 6.48 and 6.03 respectively. Postischemic cardiac function was severely impaired by isoproterenol. ATP breakdown had little influence on intracellular pH in ischemic hearts. It was verified that inotropic agents can progress ischemic myocardial injury, and that contractile recovery is more correlated with the residual ATP level than intracellular pH. PMID- 3342074 TI - Active site model of cytochrome P-450 LM2. AB - Based on (i) a detailed analysis of the physicochemical properties of selected benzphetamine derived substrates and (ii) the identification of Tyr-380 as active site residue trans to thiolate theoretical studies (computer aided molecular design) revealed a model of the substrate binding site of cytochrome P-450 LM2. The results indicate that substrates with a butterfly-like bulky conformation exhibit the highest intrinsic activity. Those substrates which preferably exist in an extended conformation are sterically hindered to intensively interact with the binding site which is demonstrated by computer graphics. PMID- 3342073 TI - Covalent change in alpha crystallin during human senile cataractogenesis. AB - The high molecular weight aggregates (HMWA) obtained from normal and cataractous human lens nuclei have been resolved by SDS-polyacrylamide gel electrophoresis, and the alpha crystallin band has been probed with antisera made against the whole alpha crystallin molecule and with antisera made against synthetic peptides of alpha crystallin (alpha A2 147-161 and alpha A2 163-173). Quantitation of these antisera binding demonstrated that the anti-alpha A2 163-173 serum and the anti-alpha whole sera bound equally well to the alpha crystallin band from the HMWA fraction from normal and cataractous lenses. In contrast, the anti-alpha A2 147-161 serum bound little, if at all, to alpha crystallin from normal lenses, while it bound well to alpha crystallin from cataractous lenses. These results demonstrate a covalent alteration in the alpha crystallin molecule, and suggest a possible location of a covalent change that may occur during the cataractogenic process in the aged human lens. PMID- 3342075 TI - Differential effect of the calmodulin inhibitor trifluoperazine in modulating cellular accumulation, retention and cytotoxicity of doxorubicin in progressively doxorubicin-resistant L1210 mouse leukemia cells. Lack of correlation between cellular doxorubicin levels and expression of resistance. AB - Calmodulin inhibitors are effective in enhancing cytotoxic effects of doxorubicin (DOX) in DOX-resistant cells, possibly by enhancing cellular levels of drug. In the present study, L1210 mouse leukemia cells adapted to grow in vitro, in the presence of 0.025 to 0.25 microgram/ml DOX, and identified as L1210/DOX0.025, L1210/DOX0.05, L1210/DOX0.1, and L1210/DOX0.25 were approximately 5-, 10-, 20-, and 40-fold DOX resistant, respectively, compared to parent-sensitive cells (L1210/S). Using a soft agar colony assay and 3-hr drug exposure, the IC50 concentration of DOX in the progressively DOX-resistant (5- to 40-fold) L1210 cells ranged from 0.25 to 2.0 micrograms/ml and from 0.08 to 0.25 microgram/ml in the absence and presence of a non-cytotoxic concentration of 5 microM trifluoperazine (TFP) respectively. Further, based on the observed in vitro cytotoxic response, the IC50 concentration of DOX in the presence of 5 microM TFP was 2.5-, 4-, 6.7- and 8-fold lower than DOX without 5 microM TFP in the L1210/DOX0.025, L1210/DOX0.05, L1210/DOX0.1, and L1210/DOX0.25 resistant sublines respectively. In contrast, the IC50 of DOX in L1210/S cells was approximately 0.05 microgram/ml with or without 5 microM TFP. Cellular accumulation of DOX was 15-50% lower in the progressively resistant L1210 sublines compared to similarly treated L1210/S cells. However, in the presence of 5 microM TFP, cellular accumulation of DOX in the L1210/DOX0.05 and L1210/DOX0.1 but not L1210/DOX0.25 was comparable to the L1210/S cells. Cellular retention of DOX in the absence or presence of 5 microM TFP was comparable in similarly treated L1210/S, L1210/DOX0.05 and L1210/DOX0.1 cells, and a 2-fold reduction in the retention of DOX in the absence versus the presence of 5 microM TFP was apparent only in L1210/DOX0.25 cells. At the IC50 of DOX in the presence of 5 microM TFP, although cellular accumulation of DOX was concentration dependent over the range of 1-20 microM TFP, enhancement in cytotoxicity of DOX was dose dependent at 1-5 microM TFP but not 5-20 microM TFP. In cells treated for 3 hr at the IC50 concentration of DOX alone or DOX plus 5 microM TFP, cellular accumulation of DOX was 7- to 14 fold and 2.5- to 3.5-fold higher, respectively, in resistant than in sensitive cells. Additionally, following treatment for 3 hr at the IC50 dose of DOX in the absence or presence of 5 microM TFP, drug retention at 3 hr was 4- to 6-fold and 1.5-fold higher, respectively, in the resistant versus sensitive cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3342076 TI - 3-(2,2,2-Trimethylhydrazinium)propionate (THP)--a novel gamma-butyrobetaine hydroxylase inhibitor with cardioprotective properties. AB - A protein fraction containing gamma-butyrobetaine hydroxylase (sp.act. 1.54 mU/mg) was isolated from the rat liver by differential precipitation with ammonium sulphate. 3-(2,2,2-Trimethylhydrazinium)propionate (THP), a noncompetitive enzyme inhibitor, when administered orally to rats for 10 days (150 mg/kg) elicited a reduction in myocardial free carnitine and long-chain acyl carnitine content by 63.7 and 74.3%, respectively. This reduction in free carnitine concentration causes a suppression of the free fatty acid oxidation, as measured by the production of 14CO2 and ketone bodies. The inhibition of fatty acid oxidation is particularly manifest when their metabolism is stimulated by feeding a fat-rich diet to the animals or in fasting rats. The inhibition of fatty acid metabolism at the stage of activation (acyl carnitine formation) can account for the cardioprotective effect of THP, which is assessed by its ability to prevent a decrease in ATP level and myocardial energy charge as well as to prevent a rise in creatine phosphokinase and lactic dehydrogenase (myocardium specific isozyme) activity in rat blood serum in response to isoproterenol and epinephrine. Regulation of the carnitine-dependent fatty acid metabolism in ischaemia is a pathogenetically justified approach to pharmacological treatment of ischaemic myocardium. In its biochemical mechanism, THP significally distinguishes itself from other known inhibitors of fatty acid oxidation. PMID- 3342077 TI - Hepatic transport of bile acids in the isolated perfused rat liver. Structure kinetic relationship. AB - We studied the transport kinetics of a series of bile acids from blood to bile in the isolated perfused rat liver in order to define better the relationship between chemical structure of bile acid molecules and efficiency of the overall hepatic transport process. BA studied were taurocholate (TC), glycocholate (GC), cholate (C), tauroursodeoxycholate (TUDC), ursodeoxycholate (UDC) and hyodeoxycholate (HDC). Estimates of intrinsic hepatic clearance (Cl(int)), maximal secretory rate (Vmax) were provided from the analysis of the relationship between bile acid removal rates and sinusoidal concentration under steady-state conditions. TC and TUDC had the highest Cl(int) (about 5 ml/min/g liver) and Vmax (about 800 nmol/min/g liver) followed in order by GC (1.71 ml/min/g liver; 442 nmol/min/g liver); C (1.25 ml/min/g liver; 252 nmol/min/g liver); HDC (0.86 ml/min/g liver; 238 nmol/min/g liver); UDC (0.72 ml/min/g liver; 176 nmol/min/g liver). The findings suggest that the efficiency of the overall hepatic transport of bile acids is highly dependent on their molecular structure and that conjugation has a more important effect on both Cl(int) and Vmax that the number or position of hydroxyl groups. PMID- 3342078 TI - H1-histaminergic activation of catecholamine release by chromaffin cells. AB - Bovine adrenal medullary chromaffin cells, prelabeled with [3H]norepinephrine, released a large proportion of cellular 3H-labeled catecholamines (CAs) when stimulated with nicotine, K+, histamine, gamma-aminobutyric acid (GABA) and several peptidic hormones [bradykinin, angiotensin II, thyrotropin releasing hormone (TRH) and neurotensin]. The histamine-induced response was dose dependent and occurred through H1 histaminergic receptors. Quantitatively and temporally the histamine- and nicotine-induced responses differed. Nicotine, during the first minutes, induced a large increase of [3H]CAs, but this response was desensitized rapidly. In contrast, histamine initially provoked a smaller release of [3H]CAs than nicotine but, with prolonged exposure (hours), a much greater response was found with histamine. Moreover, little desensitization was observed with histamine even during extended stimulation. External Ca2+ was obligatory for the histamine response, and both inorganic (Co2+ and Ni2+) and organic (verapamil, nifedipine and D-600) Ca2+ channel blockers significantly reduced release of [3H]CAs. These studies suggest that histamine as well as certain other neuroactive substances could play an important role in the physiology and biochemistry of adrenal medullary chromaffin cells. PMID- 3342079 TI - Acute effects of the aldehyde dehydrogenase inhibitors, disulfiram, pargyline and cyanamide, on circulating ketone body levels in the rat. AB - Acetonemia is generally associated with the ketogenic states of fasting and diabetes. Disulfiram (DS), an inhibitor of aldehyde dehydrogenase (AlDH) that is used as an alcohol deterrent drug, is also known to elevate blood acetone in humans, but in the absence of a commensurate increase in its metabolic precursor, acetoacetate. We reexamined the effects of DS and other AlDH inhibitors on circulating ketone body levels in male rats of Sprague-Dawley descent and again demonstrated a 6- and 16-fold increase in blood acetone along with normal levels of acetoacetate at 6 and 24 hr after DS. Pargyline, another inhibitor of AlDH, maintained normal blood acetone levels in the presence of reduced acetoacetate levels. A third inhibitor of AlDH, cyanamide, administered to fasted and nonfasted rats, elevated blood acetone levels 10-fold over controls, with, however, a commensurate 5- and 7-fold increase in blood acetoacetate levels. The threshold values for the cyanamide-induced elevation of blood acetone and acetoacetate were equivalent, i.e. approximately 0.25 mmol/kg body weight (i.p.). The elevation of acetoacetate and the inhibition of hepatic catalase activity by cyanamide are not mechanistically linked, since 3-amino-1,2,4-triazole, another inhibitor of catalase, elevated blood acetone but not acetoacetate levels. These findings suggest that DS-induced acetonemia is due to inhibition of acetone metabolism, whereas enhanced acetone formation through acetoacetate contributes significantly to cyanamide-induced acetonemia. PMID- 3342080 TI - Selective androgen insensitivity of hepatic drug-metabolizing enzymes in senescent mice. AB - The normal sexual dimorphism in murine hepatic hexobarbital metabolism (i.e. females greater than males) was found to be absent in senescent animals. Hexobarbital metabolism, expressed as microsomal activity of hexobarbital hydroxylase and hexobarbital-induced sleep time, in senescent male mice was similar to that in females, but significantly greater than that found in young adult males. No age-related changes in hexobarbital metabolism were observed in intact females. In addition, experiments involving gonadectomies and testosterone administration indicated that both male and female senescent mice were insensitive to the normally repressive effects of androgens on hexobarbital hydroxylase. In contrast, the sexual dimorphism in the activity of p-nitrophenol UDP-glucuronosyltransferase was maintained in the senescent mice as well as the usual responsiveness to testosterone regulation. Furthermore, the growth promoting effects of androgen on the kidneys and seminal vesicles were similarly expressed in young and old mice. Thus, our results suggest the development of an age-dependent and selective insensitivity of hexobarbital hydroxylase to androgenic regulation in the aging mouse. PMID- 3342081 TI - Isozyme selective arylation of cytosolic glutathione S-transferase by [14C]bromobenzene metabolites. AB - [14C]Bromobenzene was incubated with NADPH-fortified liver homogenates from phenobarbital-treated rats, after which the glutathione S-transferases were isolated from the incubation mixture. Glutathione S-transferase activity, with 1 chloro-2,4-dinitrobenzene as the substrate, in the homogenate was unchanged after incubation with bromobenzene. Radioactivity derived from the [14C]bromobenzene remained associated with the cytosolic glutathione S-transferases after DE52 and Sephadex G-100 chromatography. Further purification of the cytosolic glutathione S-transferase by CM52 and hydroxylapatite chromatography showed that bromobenzene metabolites were bound to fractions containing glutathione S-transferase subunits 4, 5, and 1. The primary site of arylation appeared to be subunit 1, as indicated by autoradiography and hydroxylapatite chromatography. [14C]Bromobenzene metabolites were not bound to microsomal glutathione S-transferases. These data show that hepatic cytosolic glutathione S-transferases, especially glutathione S transferases 4-4/5-5, 3-4, and 1-1 may act as trapping or scavenger proteins for reactive metabolites and that this effect is not associated with a loss of catalytic activity. PMID- 3342082 TI - The Meisenheimer complex of glutathione and trinitrobenzene. A potent inhibitor of the glutathione S-transferase from Galleria mellonella. AB - 1. The Meisenheimer complex formed between reduced glutathione and 1,3,5 trinitrobenzene is characterised by an extinction coefficient at 470 nm of 20400 and by an association constant at pH 9.18 of 42 l.mol-1. 2. Trinitrobenzene is a moderately good inhibitor of the glutathione S-transferase from larvae of the moth Galleria mellonella. It acts by competition with the electrophilic substrate. At pH 7.4, it has a Ki value of 10 microM. Its mode of inhibition with respect to GSH appears to be non-competitive. 3. At pH values below 9.0, the Meisenheimer complex does not appear to be formed in sufficient quantity to give significant inhibition of the enzyme. At pH 9.0 and at GSH concentrations greater than 1 mM, the inhibition of the enzyme became markedly non-hyperbolic. This was attributed to the inhibitory action of the Meisenheimer complex. The complex appears to act also by competition with the electrophilic substrate and its Ki is calculated to be 1.7 X 10(-7) M. PMID- 3342084 TI - 2,3-Dihydroxybenzoic acid is a product of human aspirin metabolism. AB - 2,3-Dihydroxybenzoic acid is present in blood plasma and urine of healthy human volunteers after aspirin ingestion. Its identity has been confirmed by mass spectrometry and by electrochemical analysis. Methods for its identification and measurement are described. The concentration of 2,3-dihydroxybenzoic acid is much lower than that of 2,5-dihydroxybenzoic acid, salicylic acid or salicyluric acid. PMID- 3342083 TI - Properties of cutaneous acetyltransferase catalyzing N- and O-acetylation of carcinogenic arylamines and N-hydroxyarylamine. AB - The role of skin for N- and O-acetylations of carcinogenic arylamine and N hydroxyarylamine was studied in vitro. Unexpectedly high activities were observed in acetyl CoA-dependent N-acetylations of 2-aminofluorene (2-AF) and p aminobenzoic acid (PABA) in skin cytosols of hamsters. The specific activity for 2-AF (4.52 nmoles/mg protein per min) was largely the same as that of rat liver cytosols. The cutaneous cytosols also catalyzed N,N-acetyltransfer reaction from N-hydroxy-4-acetylamino-biphenyl (N-OH-AABP) to 2-AF and acetyl CoA-dependent O acetylation of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu P-1), suggesting that hamster skin cytosol has enzymes similar to hepatic acetyltransferases. In addition, remarkably high correlations were observed between the skin and liver in the activities for N-acetylations of PABA and 2-AF. In a colony of Syrian golden hamsters a clear polymorphism was detected in the cutaneous N-acetylations of PABA and 2-AF. These animals were divided into three groups according to their activities: rapid, intermediate and slow acetylators. On the other hand, the acetylating activities in the skin and liver of these three groups showed monomorphic distribution with N-OH-AABP-dependent N,N acetyltransfer of 2-AF and acetyl CoA-dependent O-acetylation of N-OH-Glu-P-1. These results, together with the detection of N-acetylating activity in the skin of other experimental animals and humans, suggest that skin may play an important role in the metabolism of aromatic amines and that the cutaneous acetylation in hamsters may be under the common genetic control which regulates the individual difference in the hepatic activities. PMID- 3342085 TI - Possible role of hepatic glutathione in transport of methylmercury into mouse kidney. AB - The mechanism of the renal uptake of methylmercury was studied in mice. Preadministration of 1,2-dichloro-4-nitrobenzene (DCNB), which is a reagent that depletes hepatic glutathione (GSH) without affecting the renal GSH level, 30 min before injection of methylmercury significantly decreased the renal accumulation of mercury. The renal accumulation of mercury in mice receiving methylmercury-GSH intravenously was significantly higher than that in mice receiving methylmercuric chloride. These results suggest the possibility that hepatic GSH, as a source of extracellular GSH, plays an important role in the renal accumulation of methylmercury. No significant difference in renal mercury accumulation between bile duct-cannulated mice and normal mice was observed, indicating that the enterohepatic circulation of methylmercury is not an important factor in the renal accumulation of methylmercury in mice. Pretreatment of mice with acivicin, a potent inhibitor of gamma-glutamyl transpeptidase (gamma-GTP), significantly depressed the renal uptake of methylmercury and increased the urinary excretion of GSH and methylmercury. In in vitro reactions, methylmercury-GSH was degraded into methylmercury-cysteinylglycine by gamma-GTP, and this product was then converted to methylmercury-cysteine by dipeptidase. These results suggest that methylmercury is transported into the kidney as a complex with GSH, and then incorporated into the renal cells after degradation of the GSH moiety by gamma GTP and dipeptidase, although the methylmercury bound to extracellular GSH can be reversibly transferred to plasma proteins in the bloodstream. PMID- 3342086 TI - Drug-protein conjugates--XIV. Mechanisms of formation of protein-arylating intermediates from amodiaquine, a myelotoxin and hepatotoxin in man. AB - The enzymic and non-enzymic formation of protein-arylating intermediates from amodiaquine (AQ,7-chloro-4-(3'-diethylamino-4'-hydroxyanilino) quinoline), an anti-malarial associated with agranulocytosis and liver damage in man, was studied in vitro. [14C]AQ in phosphate buffer, pH 7.4, under air was autoxidized to a reactive derivative(s) which possessed characteristics indicative of a semiquinone/quinone imine: reduction by NADPH and ascorbic acid, conjugation with thiols and irreversible binding to microsomal and soluble proteins. Cysteinyl SH groups were major sites of arylation. Radiolabelled material irreversibly bound to HSA after 24 hr and to human liver microsomes after 4 hr represented 26.5 +/- 1.8% and 31.4 +/- 0.6% (means +/- SD, N = 3) of incubated [14C]AQ (10 microM), respectively. The quinone imine of AQ(AQQI) was synthesized, and displayed the same oxidative and electrophilic reactions as the product(s) of AQ's autoxidation. A water-soluble product formed in buffered solutions of AQ and N acetylcysteine was identified as an AQ mercapturate by comparison with an adduct prepared from synthetic AQQI. Irreversible binding of [14C]AQ was inhibited by a radical scavenger; this indicated that the semiquinone imine contributed to the binding. Although AQ was extensively de-ethylated by human liver microsomes, oxidation by cytochrome P-450 did not appear to be principally responsible for its activation and irreversible binding in microsomal incubations. AQ was oxidized to protein-arylating intermediates by horseradish peroxidase. It also formed reactive derivatives, possibly N-chloro compounds, in chlorine solutions. These findings indicated that AQ can give rise to chemically reactive species by at least three distinct mechanisms, viz. autoxidation in neutral solution under air, peroxidase-catalyzed oxidation and N-chlorination. Formation of such species in liver and myeloid cells might be responsible for the adverse reactions associated with AQ. PMID- 3342087 TI - Possible mechanism of action of SKF 64139 in vivo on rat adrenal and brain phenylethanolamine N-methyltransferase activity. AB - SKF 64139, a specific inhibitor of the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), has been widely used as a pharmacological tool for studying the characteristics of epinephrine-containing neurons. However, the mechanism of action of this drug on PNMT in vivo has not been fully elucidated. In the present study, we traced changes of PNMT activity in rat adrenal glands and medulla oblongata between 1 and 48 hr after intraperitoneal injection of SKF 64139 (50 mg/kg body wt). Within 1 hr, enzyme activity in both tissues decreased to 10% of the respective control value. However, starting at 4 hr, activity gradually recovered from the inhibition and completely returned to the respective control level by 48 hr. Removal of the inhibitor by dialysis substantially restored the adrenal enzyme activity in 1, 2 and 4 hr groups and completely returned it to control levels in 18 and 48 hr groups. A similar pattern also seemed to hold with brain extracts. The profiles of immunotitration curves, using dialyzed tissue extracts and specific antibodies to bovine adrenal PNMT, clearly indicate that, even after dialysis, a substantial amount of inactive enzyme was present in tissue extracts from 1, 2 and 4 hr groups. In contrast, by 18 hr a very small amount of inactive enzyme was present. Throughout the experimental periods there was no noticeable differences among the control and the experimental groups in the number or intensity of immunocytochemical stained neurons with PNMT antibodies of the C1 area of ventrolateral medulla. Judging from the data obtained by dialysis, immunochemical titration and immunocytochemical staining, recovery of PNMT activity following its inhibition by SKF 64139 was not due to irreversible inhibition of the enzyme followed by new enzyme synthesis. Instead, reversible binding of inhibitor to PNMT and its release were responsible for recovery. PNMT from the 1, 2 and 4 hr groups resisted further in vitro inhibition by SKF 64139 because the residual inhibitor was probably still bound to the enzyme. PMID- 3342088 TI - Effects of the antiestrogen LY 117018 on the modulation by ethinyl estradiol of the metabolism of [1-14C]oleic acid by perfused livers from normal and ovariectomized rats. AB - Intact female Sprague-Dawley rats (195-249 g) and rats that had been ovariectomized (210-285 g) were injected subcutaneously for 14 days with ethinyl estradiol (15 micrograms/kg), the antiestrogen LY 117018 (500 micrograms/kg), both drugs simultaneously, or the vehicle (sesame oil) alone. Livers were removed and perfused in vitro in a recycling system. The administration of LY 117018 alone did not affect the secretion of triacylglycerol by livers from normal rats but decreased the secretion of triacylglycerol by livers from ovariectomized rats. When the drugs were administered concurrently to either normal or ovariectomized animals, the increase in the concentration of triacylglycerol and the decrease in the concentration of cholesteryl esters in the plasma produced by ethinyl estradiol were prevented. When administered to either intact or ovariectomized rats, ethinyl estradiol alone stimulated the synthesis and secretion of triacylglycerol and cholesteryl esters by perfused livers isolated from these animals. The simultaneous administration of LY 117018 with ethinyl estradiol prevented this stimulation of the hepatic synthesis and secretion of triacylglycerol and cholesteryl esters. The depression of ketogenesis observed with livers from rats administered ethinyl estradiol alone was reversed by concurrent administration of LY 117018. The concurrent administration of the estrogen and antiestrogen did not result, however, in a complete blockade of the estrogen-induced elevation of hepatic triacylglycerol synthesis and depression of ketogenesis. The incorporation of [1-14C]oleic acid into the triacylglycerol and ketone bodies by livers from ovariectomized rats was less than that of livers from normal rats. It is clear that the antiestrogen antagonizes the actions of ethinyl estradiol on hepatic lipid metabolism. Furthermore, the use of the antiestrogen LY 117018 in these experiments allows the probable conclusion that the modulation of hepatic metabolism of fatty acid by estrogen is mediated by conventional estrogenic receptors. PMID- 3342089 TI - Formation of glutathione adducts of carbon tetrachloride metabolites in a rat liver microsomal incubation system. AB - Metabolism of CCl4 by rat liver microsomes causes damage to the membrane. GSH diminishes that damage. One mechanism of GSH protection has been characterized. It involves formation of diglutathione carbonate from two molecules of GSH and one molecule of phosgene, an oxygenated metabolite of CCl4. The present studies were done to seek other GSH adducts of CCl4 metabolites and to examine the effect of oxygen tension on their formation. Incubations were carried out in sealed flasks under oxygen concentrations ranging from 0.14 to 21% at 37 degrees. The CCl4 concentration was 72 microM. 14CCl4 and 35S-GSH were used to label metabolites. High pressure liquid chromatographic analysis of the aqueous phase demonstrated two GSH adducts of CCl4 metabolites. One adduct was oxygen-dependent and was identified as diglutathione carbonate by its co-elution with a diglutathione carbonate standard. Its formation showed no evidence of saturation when GSH concentrations as high as 10 mM were used, indicating that the overall process was nonenzymatic. Formation of the other adduct was greatest under the lowest oxygen concentration studied and none occurred at oxygen tensions of 5% or greater. Based on experiments with radiolabeled CCl4 and GSH, this metabolite appeared to be a product of one molecule each of CCl4 and GSH. Formation of this adduct had enzymatic characteristics. It was saturable with respect to GSH with an apparent Km of 70 microM, and other thiol compounds that were tested could not substitute for GSH. The adduct was unstable during isolation attempts and was not characterized further. Formation of these two GSH adducts could account for some of the protection by GSH against CCl4 injury. PMID- 3342090 TI - Intervention in free radical mediated hepatotoxicity and lipid peroxidation by indole-3-carbinol. AB - The cytoprotective effect of the natural dietary constituent indole-3-carbinol (I 3-C) on carbon tetrachloride (CCl4) mediated hepatotoxicity in mice was examined. I-3-C pretreatment by gavage 1 hr prior to intraperitoneal injection of CCl4 produced a 63% decrease in CCl4-mediated centrolobular necrosis and a related 60% decrease in plasma alanine aminotransferase activity (a marker of liver necrosis). Since the toxicological effects of CCl4 are mediated by radical species generated during reductive metabolism by cytochrome P-450, we examined the potential ability of I-3-C to scavenge reactive radicals. Three systems were used to evaluate the ability of I-3-C to intervene in free radical mediated lipid peroxidation. These systems consisted of the following: (1) phospholipid dissolved in chlorobenzene, with peroxidation initiated by the thermal and photo decomposition of azobisisobutyronitrile (AIBN); (2) sonicated phospholipid vesicles in phosphate buffer (pH 7.4), with peroxidation initiated by ferrous/ascorbate; and (3) mouse liver microsomes containing an NADPH regenerating system, with peroxidation initiated with CCl4. Lipid peroxidation was measured in these three systems as thiobarbiturate-reacting material. In the AIBN and ferrous/ascorbate systems, I-3-C inhibited lipid peroxidation, with greater inhibition under conditions of low rates of free radical generation. I-3 C was not as effective an antioxidant as butylated hydroxytoluene (BHT) or tocopherol, but it inhibited peroxidation in a dose-response manner. I-3-C was most effective as a radical scavenger in the microsomal CCl4-initiated system by inhibiting lipid peroxidation in a dose-dependent fashion, with 50% inhibition at 35-40 microM I-3-C. This concentration is about one-third of the concentration of I-3-C achieved in liver after treatment of mice by gavage with 50 mg I-3-C/kg body weight. These data suggest that I-3-C may be a natural antioxidant in the human diet and, as such, may intervene in toxicological or carcinogenic processes that are mediated by radical mechanisms. PMID- 3342091 TI - Species differences in adrenal spironolactone metabolism: relationship to cytochrome P-450 destruction. PMID- 3342092 TI - Methylglyoxal bis(cyclohexylamidinohydrazone), a novel inhibitor of polyamine biosynthesis that simultaneously inhibits S-adenosylmethionine decarboxylase and spermidine synthase. PMID- 3342093 TI - Auranofin enhances phosphorylation of putative substrates of protein kinase C in human platelets. PMID- 3342094 TI - Enzymic reduction of N-hydroxyamphetamine: the role of electron transfer system containing cytochrome b5. PMID- 3342095 TI - The effect of methimazole on bile flow and bile acid secretion in the rat. AB - The effect of methimazole on bile flow and composition was studied in male Wistar rats. Administration of methimazole as a single bolus (175-700 mumol/kg body wt) or infusion over three hours (1 mumol/100 g body wt/min) significantly increased bile flow and the biliary output of bile acids and inorganic electrolytes. Choleresis was a transient phenomenon and at the end of the experiments bile flow had returned to control values, although bile acid output was significantly lowered. When the amounts of bile acids arriving into the liver were increased by taurocholate infusion or decreased by cholestyramine pretreatment, a transitory enhancement was also found in bile flow and bile acid output, but the amounts of bile acid secreted and the choleretic effect induced were different according to the bile acid secretory rate found before methimazole administration. The bile acid content in the liver of taurocholate-infused rats was reduced during methimazole-induced choleresis. Our data indicate that the higher bile flow in methimazole-treated rats is related to an enhanced biliary secretion of bile acids probably due to a transitory stimulating effect on the transport into bile of the intrahepatocytary bile acid pool. The choleretic effect is not apparently shared by other thiocarbamide compounds. PMID- 3342096 TI - Biochemical mechanism of aminoglycoside-induced inhibition of phosphatidylcholine hydrolysis by lysosomal phospholipases. AB - Aminoglycosides such as gentamicin are hydrophilic, polycationic drugs which bind to negatively-charged phospholipid bilayers, inhibit the activities of the lysosomal enzymes involved in the degradation of the major phospholipids and cause, in kidney in vivo or in cultured cells, a lysosomal phospholipidosis. In the present study, we show that the hydrolysis of phosphatidylcholine induced in liposomes by lysosomal extracts at pH 5.4 in vitro is critically dependent on the negative charges carried by the bilayer. This hydrolysis, which is predominantly carried on by phospholipases A1 and A2, markedly increases when the phosphatidylinositol content is raised from 10 to 30% of the total phospholipids, i.e. in a range found in natural membranes. Addition of gentamicin decreases the activity of these enzymes in a non-competitive fashion, but the effect is inversely proportional to the amount of phosphatidylinositol present in the bilayer. Gentamicin and bis(beta-diethylaminoethylether)hexestrol (DEH), a cationic amphiphile which also binds to phospholipid bilayers, are equipotent inhibitors when added to negatively-charged liposomes at equinormal concentrations. Although direct aminoglycoside-enzyme interactions cannot be excluded, these results strongly suggest that gentamicin impairs the activities of the lysosomal phospholipases towards phosphatidylcholine by decreasing the available negative charges required for optimal activity. PMID- 3342097 TI - Interactions with the protein binding of 7-hydroxy-methotrexate in human serum in vitro. AB - 7-Hydroxy-methotrexate (7-OH-MTX), the major extracellular methotrexate (MTX) metabolite, is 90-95% bound in human serum, with albumin (HSA) as the major binding protein. Reports of an interaction with concomitantly administered non steroidal antiinflammatory drugs (NSAIDs) during MTX therapy led us to investigate whether these compounds could reduce the binding of 7-OH-MTX in vitro. Equilibrium dialysis experiments demonstrated that naproxen and indomethacin concentration dependently reduced the binding of 1 microM 7-OH-MTX. After ingestion of 1000 mg naproxen, per cent unbound 7-OH-MTX in sera from volunteers increased 2-3-fold in vitro, positively correlated to naproxen concentrations (P less than 0.00015). In addition, etacrynic acid, bilirubin, sulphamethizole and acetylsalicylic acid displaced 7-OH-MTX from its binding protein(s) in a competitive manner. The data suggest that 7-OH-MTX interacts with several exogenous and endogenous substances associated with HSA in human serum. Displacement of 7-OH-MTX from HSA may contribute to the interaction between NSAIDs and MTX. PMID- 3342098 TI - Effects of verapamil on the cellular accumulations and toxicity of several antitumor drugs in 9-hydroxy-ellipticine-resistant cells. AB - 9-OH-Ellipticine (9-OH-E)-resistant cells are not only resistant to the DNA topoisomerase II inhibitors, but also to some other antitumor agents, such as actinomycin D (AD), adriamycin (ADM), daunorubicin and vincristine. It was previously shown that a decreased uptake accounts for the cross-resistance of these cells to AD and ADM which then suggested that the 9-OH-E-resistant cells might display some of the properties usually associated with the multidrug resistance phenotype. In this work, we have examined the effects of verapamil, a drug which is known to overcome the multidrug resistance, on the toxicity and the cellular accumulation of four cytotoxic agents: 9-OH-E, 2N-methyl-9-hydroxy ellipticinium (NMHE), AD and ADM, either on 9-OH-E resistant cells or on a multidrug resistant subline derived from the same sensitive parental cells. Verapamil inhibited the cellular accumulation of the ellipticine derivatives in the sensitive DC-3F cells, and the toxicity of these drugs on these cells was correspondingly decreased. On either one of the resistant cell lines, verapamil had no effect on the toxicity and the cellular accumulation of 9-OH-E. In contrast, in the presence of verapamil, the cellular accumulation of NMHE by the 9-OH-E and the multidrug resistant cells was about 50% and 300% increased, respectively. The increased NMHE cellular concentration in the multidrug resistant cells was associated with an 8-fold increased toxicity. The major structural characteristics which might account for this difference between the sensitivities of both ellipticine derivatives to the effects of verapamil on the multidrug resistant cells is the presence of a positive charge on the nitrogen in position 2 of the 6H-pyridocarbazole molecule. Finally, verapamil circumvented partially the cross-resistance of DC-3F/9-OH-E cells to AD and ADM by increasing the accumulation of these drugs inside the cells. PMID- 3342099 TI - Adenosine metabolism in human whole blood. Effects of nucleoside transport inhibitors and phosphate concentration. AB - Adenosine (Ado, 10 microM) was metabolized in whole blood within 1 min, primarily to hypoxanthine and ATP. The concentration of Ado, the activities of adenosine deaminase (ADA) and Ado kinase, the Km values for Ado with ADA and Ado kinase, and the substrate inhibition of Ado kinase are factors that govern the Ado metabolism between deamination and phosphorylation. If ADA activity was blocked by 2'-deoxycoformycin (dCF, 5 microM), a tight-binding inhibitor of ADA, most of the Ado (96%) was incorporated into adenine nucleotides, whereas if Ado kinase activity was blocked with 5-iodotubercidin (10 microM), Ado was mainly (95%) metabolized into hypoxanthine. A high phosphate concentration (25 mM) caused marked increases in the formation of IMP. The nucleoside transport inhibitors dilazep (1 microM), dipyridamole (10 microM) and nitrobenzylthioinosine (NBMPR, 1 microM) strongly blocked cellular Ado metabolism. In the presence of nucleoside transport inhibitors, Ado which slowly enters the cell was metabolized principally by Ado kinase rather than ADA. Dilazep, NBMPR and dipyridamole were more effective in blocking Ado uptake and metabolism by erythrocytes suspended in a protein-free medium than by cells suspended in plasma. PMID- 3342101 TI - Effects of chronic administration of benfluorex to rats on the metabolism of corticosterone, glucose, triacylglycerols, glycerol and fatty acid. AB - (1) Rats were fed on diets enriched with sucrose, beef tallow or corn oil and treated for 11-16 days with 50 mg of benfluorex per kg of body weight. By these times the growth rate and food intake were not significantly different from those of control rats. (2) Benfluorex approximately halved the concentration of circulating triacylglycerol in rats fed the beef tallow or sucrose diets. (3) It did not significantly alter the total lipoprotein lipase activity in diaphragm, heart and adipose tissue. (4) The clearance of triacylglycerols from chylomicrons exhibited two t 1/2 values of about 0.6 and 6.9 min in rats fed the beef tallow diet. Benfluorex did not significantly alter these values. (5) Benfluorex did not significantly alter the rate of appearance of triacylglycerol in the blood of rats injected with Triton WR 1339 to block triacylglycerol uptake. It did, however, decrease the rise in circulating glucose which presumably resulted from the stress of the procedure. (6) Benfluorex decreased the extent and duration of the rise in serum corticosterone when rats maintained on the corn oil diet were fed acutely with fructose. It also decreased the circulating concentrations of glycerol, triacylglycerol and glucose after fructose feeding. (7) Rats fed on the corn oil diet and then treated with benfluorex had lower concentrations of circulating glucose, triacylglycerol, glycerol and fatty acids after being injected with 2-deoxyglucose. (8) It is proposed that some of the long-term hypoglycaemic and hypotriglyceridaemic effects of benfluorex could be mediated indirectly through changes in endocrine balance, perhaps via the serotonergic system and in particular, by decreasing the effects of stress hormones relative to insulin. The implications of these findings are discussed in relation to controlling metabolism in stress conditions and for the management of obesity, diabetes and atherosclerosis. PMID- 3342100 TI - Chronic administration of the oral hypoglycaemic agent diphenyleneiodonium to rats. An animal model of impaired oxidative phosphorylation (mitochondrial myopathy). AB - Daily subcutaneous administration of the oral hypoglycaemic agent, diphenyleneiodonium at a low dose (1.5 mg/kg body weight) over a 4-5 week period resulted in a normoglycaemic stable animal model of impaired oxidative phosphorylation in the rat. Diphenyleneiodonium specifically inhibits NAD-linked mitochondrial oxidation [Bloxham, Biochem. Soc. Trans. 7, 103 (1979)], and in isolated mitochondrial preparations from heart, soleus and gastrocnemius muscle and liver from treated animals NAD-linked respiration was reduced by 40% or more of mean control values. Brain and kidney mitochondria isolated from the treated group had similar rates of NAD-linked respiration to their respective control values. The activity of NADH-ferricyanide reductase was significantly reduced in all tissues tested, even in the isolated brain and kidney mitochondria where the activity in these tissues was 60-75% of control values. This suggests that at least 40% of Complex I activity must be inhibited before there is a decline in NAD-linked mitochondrial respiration. This paper discusses the use of diphenyleneiodonium as a means of establishing an animal model of the human disease state, termed mitochondrial myopathy. PMID- 3342102 TI - Deamination of methylamine by semicarbazide-sensitive amine oxidase in human umbilical artery and rat aorta. AB - The deamination of methylamine (MA) by amine oxidase enzymes has been studied and compared with that of benzylamine (BZ) in homogenates of rat aorta and human umbilical artery by means of a radiochemical assay to estimate the radiolabelled deaminated metabolites produced, and also a spectrophotometric assay to measure H2O2 formation during the metabolism of these substrates. The effects of various inhibitors used in these assays suggest that a semicarbazide-sensitive amine oxidase (SSAO) is predominantly if not wholly responsible for the deamination of both MA and BZ in these tissues. MA was found to have a relatively higher apparent Km (102 microM in aorta; 779 microM in umbilical artery) than BZ (6.8 microM in aorta; 207 microM in umbilical artery) for metabolism by SSAO in these tissues. However, these large differences between species in the apparent Km values for each amine indicate that the biochemical properties of SSAO in human and rat vasculature are not identical. SSAO in human umbilical artery was particularly active towards MA, with a Vmax which was approximately 70% greater than that for BZ as substrate, whereas in rat aorta the Vmax for MA was around 60% of that for BZ. MA is known to occur endogenously in man and other species, and the possibility that it may be a physiological substrate in vivo for SSAO is discussed. PMID- 3342103 TI - Effects of alpha- and beta-adrenoceptor agonists and antagonists on ATP and catecholamine release and desensitization of the nicotinic response in bovine adrenal chromaffin cells. AB - The effects of a number of alpha- and beta-adrenoceptor agonists and antagonists on the modulation of secretion from bovine adrenal chromaffin cells were investigated. Secretion was induced by nicotine, 56 mM K+, histamine or Ba2+ and was detected by the ATP luciferin-luciferase bioluminescence technique or by the measurement of endogenous catecholamines (CA) by HPLC coupled with electrochemical detection. ATP release from freshly isolated cells by 5 microM nicotine was only weakly inhibited by adrenaline and noradrenaline and even then required high concentrations (greater than 500 microM), while dopamine (1 microM 1 mM) and isoproterenol (100 microM) had no effect. Clonidine (100 microM), oxymetazoline (100 microM), yohimbine (100 microM), and propranolol (5 microM) all produced inhibition of nicotine-induced ATP release with the order of potency:propranolol greater than oxymetazoline greater than clonidine = yohimbine. The inhibitory effect by propranolol could not be reversed by high concentrations of adrenaline or isoproterenol. In chromaffin cell monolayer cultures, all alpha 2-adrenoceptor agents tested (clonidine, oxymetazoline and yohimbine), produced a dose-dependent, Na+-sensitive, non-competitive inhibition of nicotine-induced catecholamine release with little effect on the catecholamine release induced by K+ (56 mM), histamine (10 microM) or Ba2+ (2.2 mM). (+/ )Propranolol caused a similar pattern of inhibition, however, this inhibition was also observed by (+)propranolol, an isomer with little beta-adrenoceptor antagonist activity. The effects of clonidine and propranolol on desensitization of nicotine-induced CA secretion were also investigated. The degree of desensitization of the nicotinic response was dependent on the concentration of nicotine to which the cells were pre-exposed. Desensitization was detected as the decrease in response to a near EC50 concentration of nicotine (5 microM) following pre-incubation of cells to nicotine in the range of 0.3-300 microM. The desensitization had a threshold of 1 microM nicotine and was maximal at 3 microM nicotine in the pre-incubation. Both clonidine (50 microM) and (+/-)propranolol (5 microM) inhibited CA secretion induced by nicotine (0.3 microM-300 microM) during the pre-incubation period. However, regardless of this inhibition of secretion, neither clonidine nor propranolol had an effect on either the onset, or the rate of nicotine-evoked desensitization subsequently observed. These data suggest that inhibition of the nicotinic response and desensitization of the nicotinic response are regulated independently.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3342105 TI - Drug-protein conjugates--XVI. Studies of sorbinil metabolism: formation of 2 hydroxysorbinil and unstable protein conjugates. AB - The metabolism of sorbinil [+)6-fluoro-spiro (chroman-4, 4'-imidazolidine)-2',5' dione), an aldose reductase inhibitor associated with immunological adverse reactions, was studied in vivo and in vitro with particular reference to the formation of protein conjugates of 2-hydroxysorbinil and their further metabolism. [8-3H]Sorbinil was rapidly and extensively metabolized in the rat. 2 Hydroxysorbinil (2HSB) and a phenolic primary alcohol (2,4-imidazolidinedione 5 (2-hydroxyethyl)-5-(5-fluoro-2-hydroxyphenyl); IHFH) were its principal urinary metabolites; over 0-24 hr, they represented 17.0 +/- 0.7% (mean +/- SD, N = 4) and 7.1 +/- 0.7% of the dose, respectively. [3H]2HSB isolated from urine and re administered was converted to IHFH. Chronic dosing with sorbinil (150 mg/kg x 5) induced 2-hydroxylation of the drug, the 0-24 hr urinary excretion of 2HSB increasing from 17.0 +/- 0.7% to 24.7 +/- 3.4% of the dose (P less than 0.05 by Students' paired t-test). The biotransformation of 2HSB to IHFH was rationalized in terms of an open-chain aldehyde intermediate. Since aldehydes form both stable and unstable protein adducts, 2HSB was potentially a pro-reactive metabolite and initiator of the hypersensitivity reaction associated with sorbinil. However, [3H]2HSB was neither metabolized by human liver microsomes nor underwent irreversible binding to the microsomal protein. Nevertheless, the mild reductant sodium cyanoborohydride, although without effect on microsomal binding of [3H]2HSB, enhanced binding to human serum albumin. Formation of unstable Schiff base adducts was indicated. PMID- 3342104 TI - Drug-protein conjugates--XV. A study of the disposition of D-penicillamine in the rat and its relationship to immunogenicity. AB - The disposition of [14C]D-penicillamine (PA) was investigated in vitro and in vivo with male Wistar rats. Irreversible binding of [14C]PA to isolated rat plasma proteins in vitro reached a maximum of 20.6% of total radioactivity at 6 hr. Irreversibly bound [14C]PA could be dissociated with dithiothreitol, demonstrating that conjugation was via disulphide linkage. Three hours after i.v. administration of [14C]PA (27 mumol/kg) to rats 100% of plasma radioactivity was irreversibly bound, representing approximately 3.5% of the dose. Further studies on the disposition of PA-plasma protein conjugates showed that dissociation occurred readily in vivo: the plasma half-life of the conjugate was approximately 3 hr. Free [14C]PA was the major urinary metabolite after administration of both free and conjugated drug. These studies show that the disposition of PA is similar to that reported for the structurally related sulphydryl drug captopril (CP). Free PA (340 mumol/kg and 3.4 mmol/kg) administered i.p. and i.m. daily for 4 days at one monthly intervals, and also PA-KLH conjugate (100 micrograms/rat) administered by single i.p. injection at monthly intervals with and without Freund's complete adjuvant, failed to induce PA-specific IgG or IgM antibody responses detectable by ELISA. In contrast, CP (270 mumol/kg), administered by the same protocol as free PA, induced a CP-specific IgG antibody response after the third series of monthly injections. These data suggest that the difference in immunogenicity between PA and CP arises from a difference in the intrinsic immunogenicity of the haptens, rather than from their disposition. PMID- 3342106 TI - Enzyme induction produced by N-(3,5-dichlorophenyl)succinimide (NDPS) in rats. PMID- 3342107 TI - Worksite hypertension control. A guide to success. PMID- 3342108 TI - Drug testing: ethical considerations. PMID- 3342109 TI - Drug testing: a preventive approach. PMID- 3342110 TI - Can you be a manager and a leader? PMID- 3342111 TI - Worker exposure to AIDS & hepatitis B. Facts for the health care industry. PMID- 3342112 TI - Planning of movement parameters in a visuo-motor tracking task. AB - Monkeys trained to track a continuously moving visual target with a joystick do so by making a series of intermittent positional corrections rather than in a single smooth movement. The amplitude of each correction is highly correlated both with the error between the target and joystick positions, and with the velocity of the target, measured at movement onset. This velocity estimate is used to predict where the target will be by the end of each movement, and thus helps to set its amplitude correctly. To do this successfully, the monkey must know in advance how long his next movement will take. But, confusingly, the eventual duration of each movement is also highly correlated with its amplitude. So it appears that the monkeys need to simultaneously know the amplitude and duration of a movement, but cannot determine one without prior knowledge of the other. We have examined two possible solutions to this problem; only one agrees with our data. The monkeys seem to select the amplitude of their movements by scaling target velocity by a standard time constant which gives the additional distance the target will move. They then add this to the positional error estimated at or near to the start of each movement, to get the final movement amplitude. The velocity scaling value that gives the best fit to the observed amplitudes is very close to the average duration of all the monkeys movements. We therefore propose that the monkeys use a standard time constant for the purpose of calculating how far the target will move during each of their positional corrections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342113 TI - Motor somatotopy in the striatum of rat: manipulation, biting and gait. AB - The objective of this study was to examine the hypothesis of somatotopically organized motor functions in the striatum. In Experiment 1, ibotenate-induced lesions of the rostrolateral striatum in rats produced a transient decrease of ad libitum food intake, a more enduring decrease of body weight, and chronic impairments of food biting, holding of hard food pellets and feeding efficiency, with no apparent alterations of gait balance in a beam walking task. Lesions of the medial striatum had minimal or no reliable effects on any of the measured parameters. In Experiment 2, the motoric effects of ibotenate lesions restricted to either the dorsomedial or the dorsolateral or the ventrolateral regions of the rostral striatum were examined. Lesions of the dorsolateral striatum produced the most deleterious effect on holding postures of the forelimbs, whereas lesions of the ventrolateral striatum maximally affected food biting, feeding efficiency, ad libitum food intake, and body weight. No regional lesions affected gait balance. Dorsomedial striatal lesions did not affect any of the measured parameters. The findings support the hypothesis of a somatotopically organized role of the rostrolateral striatum in orofacial and forelimb motor control. PMID- 3342114 TI - Competition for sucrose-pellets in triads of male Wistar rats: the individuals' performances are differing but stable. AB - After having individually been accustomed to consume palatable sucrose-pellets, the individual's competition-rate for sucrose-pellets within its familiar triad has been observed in male Wistar rats. In this fixed-triad, food competition paradigm high-performing rats (high competition-rate, majority of pellets consumed), medium-performing rats (medium competition-rate, consumption of some pellets) and poor-performing rats (almost completely abstaining from competition with only rare incidence of pellet consumption) can be distinguished. Intra-group rank-orders, defined according to the individuals' competition-rates (expressed as a score), were present in many triads and, once established, these were stable over months. No additional differences were observed between high- and poor performing rats, neither when these were individually tested in an open field or in the elevated plus-maze, nor with regard to the preference for a sucrose solution. PMID- 3342115 TI - Are emotion and motivation localized in the limbic system and nucleus accumbens? AB - Groups of control rats without surgery or groups of rats prepared with surgical lesions of the septal nuclei, amygdala, cingulate cortex, accumbens nucleus, section of the fornix, or sham surgical operations, were tested in a simple autonomic conditioning situation (conditioned defecation). Control rats and rats with lesions of the accumbens nucleus were also tested in a straight alley maze under varying conditions of water deprivation. In general, the lesions had little effect except that amygdaloid damage impaired acquisition of conditioned defecation. The theory that 'emotion' and 'motivation' can be localized in the 'limbic system' and nucleus accumbens is discussed critically. PMID- 3342116 TI - Behavioral cross-sensitization between cocaine and enkephalin in the A10 dopamine region. AB - The motor stimulant effect produced by cocaine and the injection of opioids onto A10 dopamine neurons is thought to be mediated by an increase in dopaminergic transmission in mesolimbic dopamine terminal fields such as the nucleus accumbens. Following daily administration, the behavioral stimulant effect of both cocaine and intra-A10 injection of opioids is augmented. The data in this report demonstrate that rats receiving daily injection of enkephalin analogue into the A10 have an enhanced motor stimulant response to intraperitoneal cocaine, but not to saline. Conversely, rats receiving daily injection of intraperitoneal cocaine have an enhanced motor stimulant response to intra-A10 injection of enkephalin analogue. PMID- 3342118 TI - Revision rhinoplasty. Analysis and treatment. AB - As rhinoplasty becomes an increasingly popular procedure, the aesthetic expectations of both the facial plastic surgeon and the patient become more discriminating. Thus, the number of revision rhinoplasties increases. Of 697 rhinoplasties performed by the senior author (F.M.K.) during a three-year period, 18% of those procedures were revision surgeries. The senior author was the primary surgeon in 53% of those revision cases. This article presents an analysis of 126 consecutive revision rhinoplasty cases from that period, outlining the major deformities in a clinically meaningful system. Treatment of each problem category is discussed and representative cases are shown. The senior author's own revision rate and observations are discussed and compared with those in the medical literature. PMID- 3342117 TI - Place navigation in rats is impaired by lesions of medial septum and diagonal band but not nucleus basalis magnocellularis. AB - The role of forebrain cholinergic projections in place navigation learning was assessed in two experiments. Following surgery, rats were required to learn the spatial location of an underwater platform on the basis of distal room cues. Bilateral injections of ibotenic acid into the nucleus basalis magnocellularis depleted choline acetyltransferase (ChAT) from the anterior and temporoparietal cortex but not the hippocampus. Separate histological studies confirmed the accuracy of the lesions and demonstrated a marked loss of cortical acetylcholinesterase. These rats subsequently showed no deficits in spatial learning or memory. In a second experiment, bilateral lesions of the vertical limb of the diagonal band of Broca and medial septum depleted ChAT from the hippocampus and posterior cortex but not the anterior cortex. Histological studies confirmed the accuracy of the lesion and showed a pronounced loss of acetylcholinesterase from the hippocampus. These rats were deficient in spatial learning and showed reduced spatial bias during transfer tests. The data are discussed in the light of the hypothesis that the cholinergic innervation of the hippocampus plays a key role in spatial reference memory processes involved in place navigation. PMID- 3342119 TI - Osteocutaneous free scapular flap for one-stage mandibular reconstruction. AB - Developments in microvascular surgery have overcome much of the problem of inadequate vascularity encountered by more conventional methods of mandibular reconstruction. The advantage of the osteocutaneous scapular flap compared with earlier described revascularized bone grafts or composite flaps is its greater versatility in reconstruction of soft-tissue defects of the oral cavity concomitant with mandibular reconstruction. This is primarily related to the independent vascular pedicles of the cutaneous and osseous portions of the flap. This flap is our preferred method of reconstructing mandibular defects. PMID- 3342120 TI - Reconstruction of the larynx and trachea. AB - This article involves an analysis of 43 patients who underwent 64 reconstructive procedures for laryngeal and/or tracheal defects at The Ohio State University (Columbus). The purpose of this report is to analyze the results of a variety of reconstructive techniques in order to formulate a recommended therapeutic approach. Utilizing this therapeutic approach, 77% of the reconstructions were totally successful in providing an airway not requiring a tracheotomy tube and a voice capable of communication. Another 16% of the reconstructions were considered partially successful, requiring a permanent airway tube due to limitations created by coexisting health problems. There have been no patients where airway reconstruction was totally unsuccessful. A generalized approach to reconstruction is presented. PMID- 3342121 TI - Surgery on the buccal fat pad in masseter transfer. AB - The buccal fat pad is an essential anatomic structure in the esthetic presentation of the face. It may become hypertrophied, with fullness of the cheek, or atrophic, with a sunken appearance, or become a plus or minus factor in reconstruction in this area. Lipoma of this pad is extremely rare, but it must also be differentiated. There are, therefore, certain circumstances where the presence or absence of the buccal fat pad can create a specific imbalance and asymmetry in the face. The correction of these conditions may require reduction or augmentation. The anatomy, the risks, the classification, and the various surgical techniques that are available to accomplish this are outlined and correlated to the masseter muscle transfer. PMID- 3342122 TI - Irradiated homologous cartilage grafts. Long-term results. AB - The use of irradiated homologous cartilage for the restoration of facial contour defects remains a controversial issue in reconstructive surgery. Both favorable and unfavorable reports can be found in the literature. Some basic research concerning the rate and mechanism of resorption has been completed but has failed to resolve the issue of the usefulness of this material in day-to-day practice. One frequently cited reference concerning the use of irradiated homologous cartilage in reconstructive surgery was coauthored by two of the present investigators ten years ago. In an effort to place this study in a long-term perspective, we examined 42 of the original 107 patients who formed the initial population base. Sixty-two of the original 145 irradiated homologous cartilage grafts have been followed up for an average of nine years, with an average resorption rate of approximately 75%. Eighteen of 24 grafts followed up from 11 to 16 years completely resorbed. In spite of complete graft resorption, some patients have maintained satisfactory facial contour with fibrous tissue replacement of the cartilage. PMID- 3342123 TI - Carcinoma in situ and microinvasive squamous carcinoma of the laryngeal glottis. AB - Twenty-five patients with severe squamous intraepithelial neoplasia, grade 3 (SIN III) of the glottis were identified and followed up; three patients (12%) eventually developed invasive carcinoma and nine patients (36%) were noted to have coexisting microinvasive carcinoma. Two of the patients with microinvasive carcinoma were treated by hemilaryngectomy, three with stripping and radiation therapy, two with stripping alone, and two by radiation therapy. None of the patients developed recurrent disease after one to five years of follow-up. This observation supports the approach of treating "true" microinvasive carcinoma similar to carcinoma in situ. The 16 remaining patients were treated by stripping (ten patients), stripping and radiation therapy (four patients), and radiation therapy alone (two patients). Three patients progressed to invasive squamous carcinoma at 35, 39, and 84 months after the diagnosis of SIN III. Patients in this study displaying SIN III with or without microinvasive carcinoma were successfully treated by surgery or radiation therapy alone or by combined therapy. The finding of 12% progression to invasive carcinoma and coexisting microinvasive carcinoma in 36% confirms the preinvasive nature of SIN III of the laryngeal glottis. PMID- 3342124 TI - Measurements of oxygen pressure in the vocal fold during laryngeal nerve stimulation. AB - To clarify the mechanisms of ischemic change in the vocal fold on phonation, model experiments were performed under various conditions by recording tissue oxygen pressure (Pto2) values under electrical stimulation of either the recurrent laryngeal nerves or external branches of the superior laryngeal nerves. In addition, autonomic nerve regulation of laryngeal vessels was estimated under administration of succinylcholine chloride. Oxygen pressures of the vocal fold were measured in the lamina propria and vocal muscle at the middle of the membranous portion. The Pto2 in the lamina propria showed a slight increase during lower-frequency stimulation and a slight decrease during higher-frequency stimulation of the recurrent laryngeal nerve. The Pto2 in the vocal muscle showed a decrease during stimulation of the recurrent laryngeal nerve. On the other hand, the Pto2 showed almost no change in the lamina propria or vocal muscle during stimulation of the external branch of the superior laryngeal nerve. It is supposed that an ischemic change in the vocal muscle on phonation results mainly from contraction of the vocal muscle. On the contrary, the ischemic change in the vocal mucosa on phonation does not appear to be directly caused by the contraction of the vocal muscle but by other factors, such as wavelike movement. PMID- 3342125 TI - Depressed natural killer cell activity in cervical lymph nodes containing focal metastatic squamous cell carcinoma. AB - Natural killer (NK) cells are a subpopulation of lymphocytes involved in host defense against tumor cells. Although a great deal of clinical research has focused on the role of NK cells in the blood of patients with cancer, very little has been done to determine what role they may play at the regional or lymph node level. One hundred seven lymph nodes from 22 patients with head and neck cancer and eight control patients were assayed for NK cell cytotoxicity against the human erythroleukemia cell line K562. Six of these nodes contained a discrete intracapsular focus of metastatic tumor. Lymphocytes from these focally positive nodes exhibited a significant depression of NK cell cytotoxicity compared with all other nodes. These data suggest that the presence of metastatic tumor inhibits NK cell function at the regional level in patients with head and neck squamous cell carcinoma. PMID- 3342126 TI - Facial electroneurography. Standardization of electrode position. AB - Electroneurography is now regarded as a valuable method for quantitatively assessing facial nerve function. Controversy, however, still surrounds some aspects of the technique because of the large number of associated variables. This study establishes by experiment the optimum site for both the recording and stimulating electrodes and recommends that this be adopted as a standard to ensure consistency in results between different study groups. PMID- 3342127 TI - Evaluation of single-dose cefazolin prophylaxis for toxic shock syndrome. AB - Otolaryngologists have increased their use of parenteral prophylactic antibiotics to prevent toxic shock syndrome following nasal surgery. This rare but potentially serious postoperative complication presumably requires nasal carriage of a toxigenic strain of Staphylococcus aureus by a susceptible patient. We investigated the effect of a single preoperative dose of intravenous cefazolin on nasal carriage of S aureus. Thirty patients were studied; 15 were S aureus carriers initially and 12 (80%) remained culture positive after prophylaxis and at the time surgery was completed. We conclude that this particular regimen is unlikely to have a major effect on the incidence of toxic shock syndrome following nasal surgery. PMID- 3342128 TI - Salvage surgery for nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma is not a disease to be treated primarily by surgery. Radiation is the first choice of treatment. But, once it recurs, a second course of radiation controls only a small portion of the patients, with a high risk of accumulated radiation injury. We discuss the outcome of salvage surgery in nine cases of nasopharyngeal recurrence and 69 cases of neck metastasis that was uncontrolled or had recurred after irradiation was evaluated. A five-year survival rate of 44% for the primary lesions and 49% for the neck node metastases justifies the rationale of surgery on selected cases of radiation failure. PMID- 3342129 TI - Parotid swelling during human immunodeficiency virus infection. AB - In Europe and in the United States, bilateral parotid gland swelling has been observed as a sign of human immunodeficiency virus (HIV) infection in children, but it has not been associated with HIV infection in adults. We observed a chronic parotid gland swelling in nine HIV-seropositive patients during a nine month period in Kinshasa, Zaire. Parotid gland enlargement was bilateral in seven patients (78%), slightly painful in seven patients (78%), and painless in two patients (22%). No evidence of inflammation was observed around Stensen's duct. One of the two patients in whom a parotid gland biopsy was performed had a malignant lymphoma of the large-cell, histiocytic type. In the other patient, the parotid gland showed normal morphology with minor inflammation. Among 284 adults and 40 children with symptomatic HIV infection, chronic parotid gland enlargement was observed in none of the patients. However, two (0.7%) of the adults presented with an acute pyogenic parotitis. Further studies are needed to determine whether parotid gland enlargement is associated with HIV infection. PMID- 3342130 TI - Thyroglobulin assays in the postoperative management of differentiated thyroid cancer. AB - Carcinoma of the thyroid gland is the most common endocrine malignancy managed by the head and neck surgeon. Accepted therapy for differentiated macroscopic (greater than 1 to 1.5 cm) lesions is total or near-total thyroidectomy, followed by radioactive iodine treatment. Followup care usually consists of annual total body scan to rule out the presence of metastatic disease. Thyroglobulin, which is elaborated only by thyroid cells, either normal or metastatic, serves as a tumor marker when all functioning tissue has been ablated. The routine use of thyroglobulin assays obviates the expense and inconvenience of an annual scan. This article reviews the usefulness and limitations of serum radioimmune assays in the postoperative management of differentiated thyroid cancer. We also present several representative cases treated at our institution. PMID- 3342131 TI - Malignant transformation of nasal polyp. Case report. AB - Malignant transformation of nasal polyps is believed to be very rare. A 49-year old man had suffered from nasal polyposis and visited the hospital complaining of nasal obstruction and a huge nasal polyp in the right nostril. Histologic findings showed squamous cell carcinoma with microinvasion on the surface of the polyp and no invasion of carcinoma in the stalk. Simultaneously, malignant transformation of a small polyp was found in the left nasal cavity. Clinical and histologic findings are discussed. PMID- 3342132 TI - Pathologic quiz case 1. Extramedullary plasmacytoma of the right maxillary sinus. PMID- 3342133 TI - Pathologic quiz case 2. Peripheral odontogenic fibroma (POF). PMID- 3342135 TI - Family reactions to institutional closure. AB - Determinants of families' reactions to their relatives' relocation (from a large developmental disability institution that was closing to smaller institutions) were examined. Ninety-four families responded to two surveys sent during closure and one year later asking about (a) reactions to the closure, (b) relative's medical status, (c) involvement with their relative, (d) appraisal of the situation, and (e) social support. Over time, families reported less stress and dissatisfaction with closure. Family reactions during closure were related to the relative's medical status, involvement with their relative, and appraisal of the situation, whereas family reactions one year later were related to appraisal, involvement with their relative, and social support. PMID- 3342134 TI - Aging in the community--a matter of choice. AB - A sample of 16 older persons with mental retardation (mean age, 61 years; mean IQ, 62) who were originally studied in 1960-1961 and subsequently followed up in 1972-1973 and 1982 were reexamined. Despite advancing years, their independence, social competence, and zest for life had increased. The patterns of their lives were discussed in comparison with their counterparts who had spent their lives in more restricted residential settings. PMID- 3342136 TI - Predictors of the decision to place developmentally disabled family members in residential care. AB - Critical circumstances that predict parents' requests for residential placements for developmentally disabled persons were described. The survey sample included 154 families who placed their disabled family member and 377 families who provided care at home. Empirical findings suggest that among families who place, the disabled persons are more impaired and have more severe behavior problems than do disabled persons being cared for at home. Families who place are more likely to be larger, headed by a single parent, suffer greater disruption of family life, and receive fewer direct client services. The policy implications of these findings were discussed. PMID- 3342137 TI - Maternal communication style with mentally retarded children. AB - Mothers' style of communicating with 1- to 3-year-old mentally retarded children was related to children's communication. Mother--child communication was coded to characterize maternal communicative functions, the relationship of mother and child communication to the topic of conversation, the modality and meaningfulness of children's communication, and the manner that mothers and children reciprocate to each others' communication. Six maternal style factors were identified: attentiveness, responsiveness, persistent requesting, child-orientation, quality of requests, and quality of information. The regression of communication style factors on children's communication indicated that children were more verbal and communicatively responsive when their mothers were responsive to children's communication and focused on child-oriented topics. PMID- 3342138 TI - Adaptational features of mothers' risk and prevention appraisals after the birth of high-risk infants. AB - Sixty-seven mothers were interviewed at the time of their child's discharge from a newborn intensive care unit and 6 months after hospital discharge. After 6 months, mothers who had done more to prevent adverse pregnancy outcomes, had been more optimistic about the outcomes of their pregnancy, and saw their infant's complications as more avoidable reported greater concurrent mood disturbance and/or more distress ensuing from their child's hospitalization. Mothers' risk and prevention appraisals also played a role in their attitudes toward future childbearing, independent of mothers' reproductive history, the severity of the infants' medical condition, and the infant's behavioral difficulty at 6 months. The single most important predictor of mothers' expectations of future pregnancies, however, was whether the child was first born. PMID- 3342139 TI - Inverse relationship between the WISC-R/WAIS-R score disparity and IQ level in the lower range of intelligence. AB - The WISC-R and WAIS-R Full Scale IQs of nine groups of subjects (two from the present study and seven from previously published studies) that had mean WISC-R IQs ranging from 45 to 81 were compared. The WAIS-R produced higher IQs than did the WISC-R, and this disparity increased as WISC-R IQ decreased. A regression equation for this function was given. The progressive disparity was due in large part to differences in raw score to scaled score conversions compounded by differences in tabled values for converting scaled scores to IQs. PMID- 3342140 TI - Ratio developmental quotients from the Bayley are comparable to later IQs from the Stanford-Binet. AB - Ratio developmental quotients (DQs) from Bayley Scales administered after age 30 months were compared to Stanford-Binet IQs secured later. Means from two testings of 42 mentally retarded children were almost identical. The DQs and IQs correlated .81, p less than .001. These findings justify the use of Bayley ratio quotients to determine intellectual level of children who are too old for the Bayley norms but too retarded to earn a basal level on the Stanford-Binet. PMID- 3342141 TI - Improving the reliability of a Maladaptive Behavior Scale. AB - A methodology was described for operationalizing the terms occasionally and frequently on the Maladaptive Behavior Scale (MacDonald & Barton, 1986), previously developed by modifying Part II of the AAMD Adaptive Behavior Scale. The modal ratings obtained from staff members of 28 rehabilitation agencies were used to define numerically these terms on a revised scale; interrater reliability and item-by-item agreement were slightly greater for the revised scale. On the basis of these findings and raters' comments, it is suggested that a similar methodology might increase the reliability and usefulness of the ABS, Part II. PMID- 3342142 TI - Descriptive epidemiology of registered mentally retarded persons in Galicia (northwest Spain). AB - In a cross-sectional epidemiological study of mentally retarded persons registered in the diagnosis and therapeutic guidance centers administered by the Galician authorities, 13,636 retarded persons were identified, 9,357 of whom were severely retarded (IQ less than 50). These figures correspond to prevalence rates of 4.95 and 3.40 per 1,000, respectively. The registered retarded population was categorized by age group when diagnosed, age group on January 1, 1983, sex, level of retardation, etiological diagnosis, associated disorders, family standard of living, schooling, and educational aid received. The results, including prevalence rates, where appropriate, were compared with those reported for other countries. PMID- 3342144 TI - Tricuspid atresia with transposition of the great arteries in adolescents and adults: current state and late complications. PMID- 3342143 TI - Serial changes in the T1 magnetic relaxation parameter after myocardial infarction in man. AB - A low field resistive nuclear magnetic resonance imaging system (0.08 Tesla) was used to study the in vivo changes in the relaxation parameter T1 of the left ventricular myocardium from the first day to six months after acute myocardial infarction in 41 consecutive patients admitted to a coronary care unit. T1 maps were constructed from transverse and coronal images at various times after infarction. Thrombolytic treatment had been successful in 28 patients. Thirty three of the 34 patients studied within two weeks of infarction had a significantly increased T1 value but this developed only after the third day in four. At day 1-3 the mean (1 SD) maximum T1 was 413 (29) ms (n = 23) compared with 430 (41) ms (n = 22) at day 4-7, 433 (35) ms (n = 24) at day 8-14, 420 (34) at one month (n = 22), 388 (39) (n = 20) at three months, and 361 (24) (n = 14) at six months. The number of regions of interest with an increased T1 followed a similar time course. Although the increase in T1 measured at three months correlated with the initial maximum creatine kinase and with the left ventricular ejection fraction measured at one month, the number of regions with abnormal T1 from day 4 through to one month correlated best with left ventricular ejection fraction. There was no significant difference in T1 between patients with or without reperfusion. The rise in T1 over the first few days together with the prolonged time course of T1 increase suggests that the increase in T1 may reflect cellular infiltration as much or more than tissue oedema. PMID- 3342145 TI - Evaluation of collateral blood flow by myocardial contrast enhanced echocardiography. AB - Contrast enhanced cross sectional echocardiography is a new method for the real time evaluation of regional myocardial perfusion. Two patients with a history of anteroseptal myocardial infarction and echocardiographically detected septal dyskinesia were examined by this new method. The first patient had two severe stenoses of the left anterior descending coronary artery and normal echocontrast opacification of the interventricular septum caused by collaterals from the right coronary artery. The second patient had good patency of left anterior descending coronary artery and no septal opacification. Thus contrast enhanced cross sectional echocardiography can be used to assess the importance of collateral blood flow in the myocardium. PMID- 3342146 TI - Characterisation of the normal right ventricular pressure-volume relation by biplane angiography and simultaneous micromanometer pressure measurements. AB - The normal right ventricular pressure-volume relation was studied by recording biplane right ventriculograms with simultaneous high fidelity pressure recordings in 10 adults found to have normal coronary arteries and haemodynamic function at diagnostic cardiac catheterisation. Right ventricular volume was measured frame by frame from digitised ventriculograms by a modification of Simpson's rule. The accuracy of this method was tested in a study of 22 human and animal right ventricular casts. There was excellent agreement between calculated volumes and those measured by fluid displacement. The derived regression equations were used to correct right ventricular volumes calculated from in vivo studies. The mean (SD) end diastolic volume index for the group was 62 (13) ml/m2, the stroke volume index was 43 (8) ml/m2, and the ejection fraction was 62 (6)%. Right ventricular pressure-volume loops were generated by combining simultaneous volume and pressure curves. The normal right ventricular pressure-volume loop was triangular, departing significantly from the square or rectangle of the normal left ventricular pressure-volume loop. Ejection from the right ventricle began early during the pressure rise and continued as right ventricular pressure fell. As a result phases of isovolumic contraction and relaxation were difficult to define. These observations show that normal right ventricular pressure-volume relations differ considerably from those of the normal left ventricle, presumably reflecting the different loading conditions of the two ventricles. PMID- 3342147 TI - Continuous recording of coronary sinus oxygen saturation during atrial pacing in patients with coronary artery disease or with syndrome X. AB - Coronary sinus oxygen saturation was measured continuously during incremental atrial pacing in 34 patients undergoing cardiac catheterisation. In eleven patients with normal coronary arteriograms, negative exercise tests, and no ST segment depression on the electrocardiogram, an increase in the rate of atrial pacing transiently decreased coronary sinus oxygen saturation but within 20 s oxygen saturation returned to the control value. In six patients with coronary artery disease ST segment depression developed during atrial pacing. The coronary sinus oxygen saturation fell and remained reduced until pacing was discontinued. The size of the fall of coronary sinus oxygen saturation increased with increasing heart rate. In seven patients with coronary artery disease the ST segments were unaltered during atrial pacing and coronary sinus oxygen saturation did not fall. Ten patients with syndrome X were studied. In six ST segment depression developed on atrial pacing. In five, three of whom developed ST segment depression, the changes in coronary sinus oxygen saturation during atrial pacing were similar to those observed in patients without any evidence of coronary artery disease. In three, all of whom developed ST segment depression, coronary sinus oxygen saturation gradually increased throughout the period of atrial pacing. In two patients coronary sinus oxygen saturation fell in a manner similar to that observed in patients with obstructive coronary artery disease who developed ST segment depression on pacing. Thus regulation of coronary blood flow in normal persons in response to an increase of heart rate is rapid. Oxygen extraction across the coronary bed can increase by up to 30% and a persistent increase in oxygen extraction is an indicator of myocardial ischaemia. The term "syndrome X" does not describe a homogeneous group of patients but in the majority coronary sinus oxygen saturation does not fall despite symptoms and changes on the electrocardiogram, indicating that inadequate coronary blood flow is not the dominant mechanism. PMID- 3342149 TI - Electrocardiographic findings in myotonic dystrophy. AB - Sixty five patients with myotonic dystrophy, from a defined population in northern Sweden with an extremely high prevalence of this disease, were examined by electrocardiography. The patients were subdivided into three groups according to the severity of the disease. Abnormal electrocardiograms were found in 6 (35%) patients with mild disease, 12 (50%) patients with moderate disease, and 23 (96%) patients with severe disease. First degree atrioventricular block and left anterior hemiblock were the most commonly encountered abnormalities in patients with mild and moderate disease, whereas atrial fibrillation and flutter, abnormal Q waves, and repolarisation abnormalities were more common in patients with severe disease. This study shows that the heart is often affected by myotonic dystrophy. These effects can be detected by electrocardiography in early and mild forms of the disease. The effect on the heart is progressive and clinically important atrial arrhythmias and electrocardiographic abnormalities which are useful in differential diagnosis are common in severe forms of the disease. PMID- 3342148 TI - Occurrence and clinical significance of endocardial late potentials and fractionations in idiopathic dilated cardiomyopathy. AB - In order to assess the occurrence and clinical significance of abnormal electrograms in idiopathic dilated cardiomyopathy, endocardial electrode mapping during sinus rhythm and programmed ventricular stimulation were performed in 52 patients with or without clinical ventricular tachycardia. Abnormal endocardial electrograms were recorded in 77% of the patients and were diffusely distributed over the entire left ventricular endocardium. No relation could be established between the occurrence of late potentials or fractionations and clinical or induced arrhythmias. Endomyocardial biopsy samples were taken from 20 patients and showed that reduced myofibril volume fraction was related to the occurrence of abnormal endocardial electrograms. Neither induced arrhythmias nor the presence of late potentials or fractionations identified patients who died of sudden cardiac death during the mean (SD) follow up of 33 (11) months. Thus abnormal endocardial electrograms recorded during sinus rhythm in idiopathic dilated cardiomyopathy may only be interpreted as being a sign of damage to the myocardial cells. PMID- 3342150 TI - Latent pre-excitation: exposure of anterograde accessory pathway conduction during atrial fibrillation. AB - In three patients anterograde conduction across a previously undocumented accessory pathway was exposed by the development of atrial fibrillation. This unusual presentation illustrates the possible unmasking of the Wolff-Parkinson White syndrome by other factors in patients who have not previously demonstrated the potential for anterograde accessory pathway conduction. PMID- 3342151 TI - Infective endocarditis: incidence and mortality in the North East Thames Region. AB - A survey of infective endocarditis in the North East Thames Regional Health Authority was carried out over a period of 30 months from 1982 to 1984. The incidence, clinical characteristics, and in-hospital mortality were studied. Important causes of endocarditis were dental treatment, the presence of dental disease, drug abuse, and cytoscopy. The omission or incorrect administration of antibiotic prophylaxis in patients with valve disease was noted, but failure of correctly prescribed antibiotic prophylaxis was not recorded. Adverse prognostic features were increased age, prosthetic valve infection, Gram negative or staphylococcal infections, and aortic valve involvement. In contrast, mortality was lower in patients with mitral valve prolapse, ventricular septal defect, and streptococcus viridans infection. Deaths were usually attributable to irreversible complications present at the time of diagnosis. Vegetations were detected on the echocardiogram in half of those studied and mortality was higher in those with vegetations than without. Operation for native valve infection was associated with a low mortality and it is likely that the overall mortality for infective endocarditis has been improved by surgical intervention. PMID- 3342152 TI - Protein-losing enteropathy caused by baffle obstruction after Mustard's operation. AB - Three patients developed protein-losing enteropathy caused by intra-atrial obstruction of the systemic venous return after Mustard's operation. The enteropathy resolved in one case after reoperation and in the others after balloon dilatation of the stenosed caval pathways. Protein-losing enteropathy may occur as a complication of Mustard's operation. Balloon dilatation of the obstructed baffle is an effective alternative to reoperation. PMID- 3342153 TI - Myocardial rupture in acute myocardial infarction: urgent management. AB - Myocardial rupture complicated acute myocardial infarction in a 50 year old man. Resuscitation was started immediately and he was treated with pericardiocentesis and a massive intravascular infusion of fluid. The torn area was plicated with Teflon felt and reinforced with an uninterrupted suture. The postoperative course was uncomplicated. This report points out the crucial importance of prompt clinical recognition and management of the acute stage of cardiac rupture in acute myocardial infarction. PMID- 3342154 TI - Wolff-Parkinson-White syndrome: inadvertent permanent ablation of the accessory pathway during electrophysiological study. AB - A case of permanent unintentional ablation of an accessory pathway during electrophysiological study is reported. Possible factors predisposing to such ablation include the location and depth below the endocardium of the accessory pathway. PMID- 3342156 TI - Regression of coronary atherosclerosis: is it possible? PMID- 3342155 TI - Marfan's syndrome and isolated aneurysm of the abdominal aorta. AB - A 43 year old woman presented with an aneurysm of the abdominal aorta. Marfan's syndrome was diagnosed as the underlying cause of the aneurysm. An isolated aneurysm as presenting sign of Marfan's syndrome is rare. In a review of published reports about 30 cases were found. PMID- 3342157 TI - Laser recanalisation of coronary arteries by metal-capped optical fibres: early clinical experience in patients with stable angina pectoris. AB - The delivery of laser energy to the coronary circulation by bare optical fibres may cause perforation of the vessel. Experimental studies have shown that this complication can be avoided if the optical fibre is fitted with a metal cap to prevent the potentially dangerous forward projection of the laser beam. This study was performed to assess the feasibility and short term effects of percutaneous coronary laser recanalisation with these modified fibres. Recanalisation of a severe stenosis of the left anterior descending artery was attempted in six patients who were referred for coronary artery bypass grafting. Although the percutaneous technique was used, the laser procedure was performed during coronary bypass surgery before the start of cardiopulmonary bypass to minimise the effects of potential complications. A 1.5 mm diameter metal-capped fibre coupled to an argon laser was advanced percutaneously over a guide wire positioned across the stenosis. In the first patient the delivery of 152 J resulted in the gradual passage of the fibre through a 3 cm long stenosis. Repeat angiography showed a reduction in the severity of the stenosis. In the second patient the delivery of 112 J failed to allow fibre advancement; a further 80 J pulse caused perforation which was repaired. In the remaining four patients the delivery of laser energy in the attempt to traverse the stenosis was limited to less than 90 J. In two of the four patients the severity of stenosis was reduced. No further complications were seen. Percutaneous coronary laser recanalisation with metal-capped optical fibres is feasible but improvements of currently available technology are needed to increase the primary success rate. PMID- 3342158 TI - Enzyme tests in the evaluation of thrombolysis in acute myocardial infarction. AB - The activity of alpha-hydroxybutyrate dehydrogenase, creatine kinase, creatine kinase MB and aspartate aminotransferase was measured on serial plasma samples from patients with acute myocardial infarction. The study was part of a multicentre randomised trial of the effect of thrombolytic treatment in the acute phase of acute myocardial infarction. The applicability and comparability of enzyme tests for the estimation of myocardial injury were studied in 76 control patients and 74 patients treated with streptokinase. Treatment with streptokinase caused a considerable acceleration of enzyme release after acute myocardial infarction, both in patients with persistent coronary occlusion and in those with successful reperfusion. But this changed pattern of enzyme release did not affect the rate of enzyme elimination from plasma or the released proportions of different enzymes. Thus the assessment of infarct size by measurement of these enzyme activities can also be applied to patients treated with streptokinase. Moreover, the enzymes measured in the present study are all equally valid markers of myocardial injury. PMID- 3342159 TI - Prognosis and thallium-201 scintigraphy in patients admitted with chest pain without confirmed acute myocardial infarction. AB - Exercise and rest thallium scintigraphy and exercise electrocardiography were performed after discharge in 158 patients aged less than 76 years admitted with chest pain in whom a suspected diagnosis of acute myocardial infarction had not been confirmed. During a follow up of 12-24 months (median 14 months) there were 10 cardiac events--that is, non-fatal acute myocardial infarction or cardiac deaths. Transient thallium defects and abnormal ST response (that is ST segment deviation or uninterpretable ST segment) during exercise were correlated significantly with an unfavourable prognosis. One hundred and four patients with neither of these characteristics were at lower risk of a cardiac event than the 19 patients with both of these characteristics. The percentages of patients in these two groups without a cardiac event after one year were 98.1 and 78.8 respectively. Thallium scintigraphy, alone or in combination with exercise electrocardiography, can be used to identify groups at high and low risk of future cardiac events, in patients with chest pain in whom acute myocardial infarction is suspected but not found. PMID- 3342160 TI - Coronary thrombosis and platelet/fibrin microemboli in death associated with acute myocardial infarction. AB - The frequency and clinical significance of platelet/fibrin microemboli in the microcirculation were investigated in 24 patients whose deaths (before and during hospital admission) were associated with acute myocardial infarction. An acute coronary thrombus was present in all the hearts. In nine hearts an acute thrombus was found in more than one major epicardial coronary artery. A total of 35 acute thrombi were found in the 24 hearts. Platelet/fibrin microemboli were found in 19 (79%) hearts. Eighteen patients died in hospital. The hearts of 16 of these cases showed microemboli; 16 had important arrhythmias or various forms of heart block; 13 showed acute pathological changes in the conduction system. Fourteen of the deaths in hospital were primarily the result of cardiogenic shock and four were primarily caused by arrhythmia. Six of the deaths that occurred before admission to hospital were regarded as being arrhythmic in origin. Three of these showed microemboli and the other three had acute pathological changes in the conduction system. Microemboli were found in two (24%) of 12 control hearts. Coronary thrombosis was found in most deaths caused by acute myocardial infarction and platelet/fibrin microemboli were present in the majority of such hearts. These may arise from the coronary thrombus in the larger upstream vessel supplying the microcirculation. PMID- 3342162 TI - Extrapolated maximal oxygen consumption: a new method for the objective analysis of respiratory gas exchange during exercise. AB - Respiratory gas exchange was measured during maximal treadmill exercise testing in six healthy volunteers and 20 patients with chronic heart failure. A curve of equation y = ax-bx2 was used to model the relation between the rate of oxygen consumption (y axis) and the rate of carbon dioxide production (x axis). The constants "a" and "b" were used to calculate the maximal value of the expression ax-bx2. This value was termed the "extrapolated maximal oxygen consumption". For all subjects a close fit between experimental data and mathematical model was obtained and the values of the measured maximal rate of oxygen consumption and "extrapolated maximal oxygen consumption" were similar. Respiratory gas exchange was reanalysed using only those values obtained during the first 90%, 75%, and 66% of exercise. In contrast with the value for the measured rate of oxygen consumption, the value of "extrapolated maximal oxygen consumption" was effectively independent of exercise duration. Extrapolated maximal oxygen consumption provides an objective measure of cardiorespiratory functional reserve that, within limits, is independent of exercise duration. Extrapolated maximal oxygen consumption is complementary to the direct measurement of the maximal rate of oxygen consumption and increases the amount of information derived from a single exercise test. PMID- 3342161 TI - Prevalence of ischaemic heart disease: the Caerphilly and Speedwell surveys. AB - Mortality from ischaemic heart disease remains high in the United Kingdom, and the present report describes the prevalence of the various epidemiological manifestations of the disease in two recent community studies with a common core protocol, each containing samples of over 2000 men, carried out in South Wales (Caerphilly) and the West of England (Speedwell, Bristol). The prevalence of electrocardiographic evidence of ischaemia was similar in the two communities- 8.7% of men aged 45-49 years rising to 18.6% in men aged 55-59 years in the samples from South Wales, and 8.0% and 17.2% respectively in the Bristol population. The overall prevalence of angina was 7.7% in Caerphilly and 7.8% in Speedwell in men aged 45-59 years, but symptoms of severe chest pain were more commonly reported in South Wales than in Speedwell (10.1% compared with 6.3%). The data, however, suggested that the overall prevalence of ischaemic heart disease was very similar in the two areas. The prevalence of ischaemic heart disease was compared with that found in other population studies carried out in the United Kingdom and was higher than that found when employed men only were studied. There were substantial differences in mortality between the two areas; possible reasons for this are differences in community or medical services, smoking habit, or unemployment rates. PMID- 3342163 TI - Percutaneous balloon dilatation of calcific aortic valve stenosis: anatomical and haemodynamic evaluation. AB - Two groups of elderly patients with calcified aortic stenosis were treated by balloon dilatation. In group 1, the valve was dilated just before surgical replacement of the valve. The valvar and annular changes occurring during dilatation were examined visually. In 20 of the 26 patients in this group there was no change. In the six remaining patients mobilisation of friable calcific deposits (1 case), slight tearing of the commissure (4 cases), or tearing of the aortic ring (1 case) were seen. Dilatation did not appear to alter valvar rigidity. In 14 patients (group 2) the haemodynamic gradient across the aortic valve was measured before and immediately after dilatation and one week after the procedure. Dilatation produced an immediate significant decrease of the aortic mean gradient and a significant increase of the aortic valve area. Eight days later the mean gradient had increased and the aortic valve area had decreased. Nevertheless there was a significant difference between the initial gradient and the gradient eight days after dilatation. The initial aortic valve area was also significantly larger than the area eight days after dilatation. The aortic valve gradient rose significantly in the eight days after dilatation and at follow up the gradients were those of severe aortic stenosis. PMID- 3342164 TI - Possible role of coronary spasm in acute myocardial infarction precipitated by hyperventilation. AB - Acute myocardial infarction was precipitated by hyperventilation in a 65 year old man. His coronary arteriogram in the chronic phase showed almost normal coronary arteries. Injection of acetylcholine (50 micrograms) into the left coronary artery induced spasm of the circumflex artery with chest pain in association with ST-segment elevation in the inferior leads and ST-segment depression in the precordial leads. In this patient there may have been atherosclerosis of the coronary arteries with absent or dysfunctional endothelium, despite an almost normal angiographic appearance. In the absence of endothelium the response of the smooth muscle to acetylcholine is constriction. PMID- 3342165 TI - Abolition of exercise induced ST depression after exercise training and its recurrence after beta blockade. AB - Exercise training can improve angina. A patient whose exercise tolerance test became normal after a year on an exercise programme nevertheless had a positive exercise test when he was taking a beta blocker. These results suggest that it may be undesirable to use beta blockers in patients with angina who are on exercise programmes. PMID- 3342166 TI - Unusual manifestations of arrhythmogenic right ventricular dysplasia as ventricular fibrillation, atrial paralysis, and hypoexcitable right ventricle. AB - Ventricular fibrillation occurred in an apparently healthy 19 year old man. The results of non-invasive and invasive studies suggested right ventricular dysplasia. Electrophysiological studies showed atrial paralysis, hypoexcitability of multiple areas of the right ventricle, and inducible poorly tolerated ventricular tachycardia. PMID- 3342167 TI - The surgical treatment of restrictive cardiomyopathy in pseudoxanthoma elasticum. AB - A patient with pseudoxanthoma elasticum presented in pulmonary oedema with restrictive left ventricular cardiomyopathy caused by calcified endocardial bands that were confirmed on echocardiography and at catheterisation. The bands were resected as far as possible and the involved mitral valve was replaced by a heterograft. A year later calcification of the heterograft forced its replacement by a St Jude prosthesis. Relief of symptoms has been good in the medium term. PMID- 3342168 TI - Hydroa vacciniforme: a review of ten cases. AB - Ten patients with hydroa vacciniforme are reported. The condition appears to be a distinct clinical and histological entity. Haematological, biochemical, immunological, bacteriological and viral investigations were negative. Three patients demonstrated low minimal erythema doses (MEDs) following monochromatic ultraviolet (UVA) irradiation of back skin; such UVA sensitivity may be a feature of hydroa vacciniforme. Treatment was unsatisfactory, although spontaneous improvement in the condition tended to occur and regular application of sunscreens with high protection factors against both UVA and UVB was helpful. PMID- 3342169 TI - Angiosarcoma arising in an angiomatous naevus following irradiation in childhood. AB - We describe a patient who developed an angiosarcoma on her face at the age of 24. The tumour arose from an angiomatous naevus that had been treated with radiotherapy when the patient was 7 months old. PMID- 3342170 TI - Pseudoainhum and erythropoietic protoporphyria. AB - We report the development of pseudoainhum in a patient with erythropoietic protoporphyria, the first report, to our knowledge, of these two unusual conditions occurring together. An excellent cosmetic and functional result was achieved with a Z plasty. PMID- 3342171 TI - Malignant atrophic papulosis (Degos' disease)--diffuse involvement of brain and bowel in an African patient. AB - We report pathognomonic skin lesions of malignant atrophic papulosis, accompanied by lethal central nervous system and gastrointestinal disease in a 22-year-old black man. Histopathological studies of the brain and colon showed areas of infarction and an underlying vasculitis with leukocytoclasis. PMID- 3342172 TI - Halo dermatitis around a melanocytic naevus: Meyerson's naevus. AB - A case of halo dermatitis (eczema) around a pigmented naevus is reported. This appears to be a not uncommon condition which is not described in major dermatology textbooks. The relevant literature is reviewed, and the eponym 'Meyerson's naevus' is suggested. PMID- 3342173 TI - Etretinate and nodular prurigo. PMID- 3342174 TI - The presence of neutrophils in human cutaneous ultraviolet-B inflammation. AB - We report the first observation of neutrophils in the dermal inflammatory infiltrate in human skin soon after moderate ultraviolet-B (UVB) irradiation. Thus human UVB-induced cutaneous inflammation, in this as in other respects, appears to resemble other human acute inflammatory responses to injury. PMID- 3342175 TI - Lichen sclerosus et atrophicus and autoimmunity--a study of 350 women. AB - A study of autoimmune related phenomena in 350 women with histologically confirmed lichen sclerosus et atrophicus revealed that 21.5% had one or more autoimmune related diseases, 21% had one or more first degree relatives with an autoimmune-related disease, 42% had an autoantibody at a titre greater than 1:20, and 59.5% had one or more of these autoimmune-related phenomena. No statistically significant differences in the natural history of lichen sclerosus et atrophicus were demonstrated between those patients with autoimmune-related phenomena and those without. PMID- 3342176 TI - Candida onychomycosis--an evaluation of the role of Candida species in nail disease. AB - Nail infections caused by Candida species are normally associated with chronic paronychia or chronic mucocutaneous candidiasis (CMCC). However, the role of Candida in the pathogenesis of other primary nail dystrophies has been questioned in view of their response to antifungal therapy alone. In the present study of 86 patients with primary nail dystrophies from which Candida was isolated, three patterns of nail involvement were found. Nineteen patients, of whom 17 had CMCC, had total dystrophic onychomycosis of at least two nails. The second group consisted of 27 patients with paronychia and lateral onycholysis. In a further 40 patients, who did not have paronychia, Candida was isolated from nails showing primary distal and lateral onycholysis. These changes were mainly seen in patients with peripheral vascular disease, particularly Raynaud's disease, or Cushing's syndrome. Nail biopsies from patients in the latter two groups confirmed the presence of yeasts and mycelium in the nail plate and 17 (46%) of those receiving antifungal therapy with ketoconazole or itraconazole showed complete clearance of the nail dystrophy. Good responses to therapy were seen more frequently in patients with peripheral vascular disease or Cushing's syndrome of whom 15 (72%) recovered; distal erosion of the nail plate, mycelium in the nail plate on biopsy or direct microscopy together with the isolation of C. albicans were all associated with good responses to antifungals. In addition to patients with CMCC or paronychia, therefore, Candida appears to be a significant pathogen in some patients with primary onycholysis of the finger nails, particularly where there is underlying peripheral vascular disease or Cushing's syndrome. PMID- 3342177 TI - Oestrogen and progesterone receptors in lentigo maligna. AB - We have measured oestrogen and progesterone binding in specimens of histopathologically confirmed lentigo maligna (LM) lesions excised from five elderly white men, using a dextran-coated charcoal method. Oestrogen binding was observed in four of the five specimens, and progesterone binding in all five. Marginal normal skin showed only non-specific binding for oestrogen and progesterone. The presence of steroid hormone receptors in LM suggests the possibility that hormone responsiveness may be relevant in the transformation of a lentigo maligna into malignant melanoma. PMID- 3342178 TI - Polymorphic light eruption sine eruption. AB - We describe seven patients, four female and three male, who developed intense pruritus on sun-exposed skin without visible change. The clinical features resembled those of polymorphic light eruption (PLE) without rash. Four patients also occasionally developed typical PLE upon sun exposure, but sun-induced pruritus alone occurred most frequently. No patient was taking any drug therapy. One patient developed similar pruritus following solar simulated irradiation, and one following PUVA therapy. All other laboratory investigations were negative. Treatment with low dose UVB phototherapy or PUVA therapy was effective. The condition, which we have called polymorphic light eruption sine eruptione (PLESE), appears to be a variant of PLE not previously reported. PMID- 3342179 TI - Evaluation of a therapeutic concentration of dithranol in the mouse-tail test. AB - A study of dithranol ointment in the mouse-tail test showed that 0.2% dithranol ointment induced a granular layer and orthokeratosis in mouse-tail epidermis. This provides further evidence of the value of the mouse-tail test in evaluating anti-psoriatic activity of topical preparations. PMID- 3342180 TI - Benzocaine--an unsatisfactory indicator of topical local anaesthetic sensitization for the U.K. AB - Three thousand consecutive patients undergoing patch tests were tested with a mix of benzocaine, amethocaine hydrochloride and cinchocaine hydrochloride. Eighty four subjects (2.8%) were found to be allergic to this mix. Forty of these were patch tested with the constituents of the mix: 21 (52.5%) patients were sensitive to amethocaine hydrochloride or cinchocaine hydrochloride or both, but not to benzocaine. We recommend that a non-irritant 'caine mix' containing benzocaine, cinchocaine and amethocaine should be included in the standard patch test series for the U.K. PMID- 3342181 TI - Psychiatric research in occupational medicine: the future of an illusion? PMID- 3342182 TI - Welders' pneumoconiosis: tissue elemental microanalysis by energy dispersive x ray analysis. AB - Histological examination on lung tissue obtained from 10 symptomatic welders was performed by two certified pathologists without the knowledge of the patients' clinical condition. In all cases, there was some degree of interstitial fibrosis; in five the degree of fibrosis was considered to be moderate to pronounced. The tissue was also analysed by energy dispersive x ray analysis and elemental contents were compared with age matched controls. There was a large amount of iron in the lungs of welders but the silicon content did not differ from the control subjects. No specific foreign element was detected. It is concluded that (1) interstitial pulmonary fibrosis is seen in some welders and (2) the cause of fibrosis does not appear to be coexisting silicosis. PMID- 3342183 TI - Risk of malignant lymphoma in Swedish agricultural and forestry workers. AB - The risk of malignant lymphoma after possible exposure to phenoxy acid herbicides was studied in 354,620 Swedish men who, according to a national census in 1960, were employed in agriculture or forestry. The cohort was divided into subcohorts according to assumed exposure and compared with 1,725,645 Swedish men having other economic activities. All were followed up in the Cancer-Environment Register between 1961 and 1979. Non-Hodgkin lymphoma was found in 861 men in the study cohort. The relative risk was not significantly increased in any subcohort, did not differ significantly between the subcohorts, and showed no time related increase in the total cohort or any subcohort. Hodgkin's disease was found in 355 men in the study cohort. Relative risks significantly higher than unity were found among fur farming and silviculture workers where the relative risks were 4.45 and 2.26, respectively. All five cases in the former group were engaged in mink farming. A time related rising trend in relative risk was found in the silviculture subcohort. Elsewhere the relative risk did not diverge from unity and no time related trend was discernible. PMID- 3342184 TI - Farming and malignant lymphoma in Hancock County, Ohio. AB - Raised death rates have been reported for non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) among white male residents of Hancock County, Ohio, United States, for 1960-79. As a surveillance activity, to assess the possibility of workplace exposures contributing to these raised rates, a case-control study was conducted using death certificate records of white male Hancock County residents for 1958-83. There were 61 cases of NHL, 15 cases of HD, and 304 control subjects (chosen as a stratified random sample) in the study. Cases and controls were compared with respect to their usual occupation and industry statements on the death certificates, adjusting for age at death and year of death. Summary odds ratios (OR) and test-based 95% confidence intervals (CI) were calculated. NHL was associated with the occupation of farmer (OR = 1.6; CI = 0.8, 3.4; observed number of exposed cases (Obs) = 15). The association was restricted to 1958-73 (OR = 2.1; CI = 0.9, 4.8; Obs = 13). The three cases of HD among farmers occurred in a cluster in the 15-64 age range during 1958-63 (OR = 21.2). The results for occupations and industries other than farming were based on small numbers and were unremarkable. This small study adds to the growing body of reports linking farming and malignant lymphoma, particularly NHL. PMID- 3342185 TI - Validity of self reported work history. AB - Many epidemiological studies of the relation between work and disease use information on work history obtained by interview from the study subjects. A validation study was undertaken to evaluate the accuracy of this information collected from 100 workers in a shipbuilding industry. The information furnished by the workers was compared with that present in the company's registers. The work history (job titles and starting dates) was relatively accurate and the validity varied with the number of events to declare and with their duration; it also depended on the type of information and the precision required. PMID- 3342186 TI - Vasoconstrictor response to cold in forestry workers: a prospective study. AB - In a five year prospective study of the vasoconstrictor response to cold 37 forestry workers were investigated in 1978 and again in 1983. The subjects were classified into three groups: group A (n = 13): no subjective finger symptoms in 1978 and continued sawing until 1983; group B (n = 12): no symptoms in 1978 and stopped sawing before 1983; group C (n = 12): vibration induced white finger (VWF) in 1978. A cold provocation test measuring the finger systolic blood pressure with a cuff and strain gauge technique during combined body cooling and finger cooling to 30 degrees, 15 degrees, and 6 degrees C was applied to all subjects at both investigations. In 1978 all groups had an increased cold response when compared with that of 20 non-exposed controls (p less than 0.05), and the response was more exaggerated in group C than in groups A and B (p less than 0.01). From 1978 to 1983 the vasoconstrictor response increased in group A (p less than 0.05), was in group B (p greater than 0.10), and improved in group C (p less than 0.05). The changes in cold response in groups A and C were significantly larger than the within day variation of the method (p less than 0.01). The aggravation of group A indicates that a further five years use of anti vibration chain saws induced an increased hyperreactivity in the vasoconstrictor mechanisms but led to subjective symptoms of VWF in only one subject. The improvement in group C was in accordance with the improvements of subjective finger symptoms and was associated with a previous shift from saws without vibration damping devices to anti-vibration saws and with cessation of work. The results of group C indicate that VWF may improve or subjectively disappear if exposure to vibration is reduced or stopped. The cold provocation test was more sensitive than the Taylor-Pelmear stage assessments (p<0.05). The test may be of guidance in evaluation preventive measures. PMID- 3342187 TI - Irregularly shaped small shadows on chest radiographs, dust exposure, and lung function in coalworkers' pneumoconiosis. AB - The predominant shapes of small opacities on the chest radiographs of 895 British coalminers have been studied. The aims were to determine whether irregular (as distinct from rounded) small opacities can be identified reproducibly, whether their occurrence is related to dust exposure, and whether they are associated with excess prevalence of respiratory symptoms or impairments of lung function. Six of the doctors responsible for regular radiological surveys of all British coalminers each classified all 895 radiographs twice and independently, using the International Labour Organisation's 1980 classification system. The majority view was that 39 films showed predominantly irregular small opacities, 131 showed predominantly small rounded opacities, and 587 showed no small opacities. Readers' opinions varied about the presence and shapes of shadows on the other 138 films. In general, consistency between readers (and within readers on repeated viewings) was satisfactory. The occurrence and profusion of irregular shadows were related significantly both to the men's ages and additionally to their cumulative exposure to respirable coalmine dust as determined from 15 years' dust monitoring close to where the miners had worked. For any given level of exposure, the average level of profusion of the small irregular opacities was less than the corresponding profusion of small rounded opacities. The prevalence rates of chronic cough and phlegm, and of breathlessness, were higher in those with small irregular opacities than in those with no small opacities (category 0/0), but the differences were not statistically significant after adjustment for other factors including smoking habits. The presence of irregular (but not rounded) small shadows was associated with an impairment in respiratory function averaging about 190 ml deficits in both FEV1 and FVC. These deficits were not explicable in terms of the men's ages, body sizes, and smoking habits and they were in addition to the lung function losses attributable to the miners' dust exposure as such. It is concluded that the presence and profusion of small irregular opacities should be taken into consideration when assessing the severity of coalworkers' simple pneumoconiosis. PMID- 3342188 TI - Prematurity and work in pregnancy. AB - The frequency of low birth weight (less than or equal to 2500 g) and of preterm birth (less than 37 weeks) was studied in 22,761 single live births in relation to maternal employment, taking account of 11 nonoccupational confounding factors. There was some increase of low statistical significance in both types of prematurity in service and manufacturing sectors of industry. A substantial excess of preterm births was seen in women employed in food and beverage service (O/E = 1.29, p = 0.03) and psychiatric nursing (O/E = 2.47, p less than 0.01) and of low birth weight in food and beverage service (O/E = 1.30, p = 0.02), in chambermaids and cleaners (O/E = 1.42, p = 0.03), and in those employed in the manufacture of metal and electrical and certain other goods (O/E = 1.57, p less than 0.01). Heavy lifting and long hours of work were consistently related to both outcomes, changing shift work less consistently. Noise was associated with low birth weight in the health and manufacturing sectors. The findings of this study are unlikely to have resulted from subject or observer bias but the role of unidentified factors related to selection for work are difficult to assess. PMID- 3342190 TI - Application of a job-exposure matrix to national mortality statistics for lung cancer. PMID- 3342189 TI - Mortality of workers at acetylene production plants. AB - To reduce the risk of explosion oxyacetylene cylinders are filled with a spongy mass, acetone is added to saturate the mass, and acetylene is pumped into the cylinder. The first cylinders manufactured before 1936 used a kapok filling topped off with about 16 oz of crocidolite asbestos, with a metal gauze thimble inserted to reduce risk of flash back. Cylinders must be examined annually. The use of crocidolite ceased in 1972 and other fillings have been adopted since 1970; kapok cylinders now constitute less than 5% of the total stock. To assess possible hazards, a mortality study of workers first employed between 1935 and 1975 and followed up to December 1984 was undertaken. Simulation tests showed low concentrations of asbestos in the air even in the earliest period. The population studied consisted of 370 workers at the Bilston plant in the West Midlands, 611 at the 14 other plants in England and Wales, and 120 in Scotland. No deaths occurred from mesothelial tumours but there was an excess of deaths from cancer, particularly lung cancer, cancer of the stomach, and cancer of the pancreas, the latter accounting for eight deaths. Risks appeared to be concentrated at the Bilston plant. The importance of these findings is discussed. PMID- 3342191 TI - Aesthesiometric threshold changes over the course of a workshift in miners exposed to hand-arm vibration. AB - The objective of this study was to investigate whether aesthesiometric threshold changes occur over the course of a workshift in vibration exposed hard rock miners relative to workers unexposed to vibration during the shift. The subjects were 99 miners and 40 smelter workers; four subjects declined to participate and nine were excluded from the analysis because of apparent failure to comprehend the testing procedure. Two point discrimination and depth sense aesthesiometry were conducted at the beginning and at the end of the workshift in all digits of both hands excluding the thumbs. In addition to the use of a vibrating tool during the shift, age, digital temperature, signs of arm injury, presence of fingertip callus, and handedness were documented. In the analysis the difference between postshift and preshift readings was studied in relation to these variables, particularly exposure to the jackleg drill during the shift. With the exception of exposure of the jackleg drill, no associations were observed between these variables and change over the workshift in aesthesiometric results, on both unadjusted comparison of means and backward elimination regression analysis. A statistically significant association, however, was found between the use of a jackleg drill and change in two point discrimination and in depth sense aesthesiometric results over the course of the shift, for the right hand. Evidence of the occurrence of a learning effect, particularly for two point discrimination aesthesiometry, was observed. The occurrence of an effect in the right, but not the left, hand reflects dominant handedness and relatively greater vibration exposure in the right hand in our subjects. This study supports the incorporation of an exposure free interval before aesthesiometric testing of vibration exposed workers. PMID- 3342192 TI - Decrease of erythrocyte and glomerular membrane negative charges in chronic cadmium poisoning. AB - Negative charges on red blood cell membranes were measured by the alcian blue binding test in 11 workers with high exposure to cadmium. Compared with 12 age matched control subjects, cadmium workers showed a significant decrease in red blood cell charge, which on average paralleled both the cadmium body burden and protein excretion. Animal data confirm these observations and also show that the loss of red blood cell charge caused by chronic cadmium poisoning is irreversible and associated with a loss of glomerular negative charges. The present study suggests thus that cadmium can increase the urinary excretion of anionic macromolecules such as albumin by reducing the glomerular polyanion charge. PMID- 3342193 TI - Lung function in West Sussex firemen: a four year study. AB - Although firefighting is a hazardous occupation, published evidence of long-term lung damage in firemen is inconsistent. A group of 96 men from the West Sussex Fire Brigade, which covers a simi-rural, semi-urban area, were followed up for between one and four years. They included 31 non-smokers, 40 smokers, and 25 ex smokers. After four years 12 firemen had been lost to the study. A control group of 69 volunteers, consisting of non-smoking men from various other occupations, were followed up in parallel. Lung function tests, covering a wider range than has been previously used in similar studies, were repeated six monthly for two years and annually for a further two years. The results were expressed in terms of the rate of change with time of the lung function variables. Many of the variables deteriorated in both firemen and controls, but the rate of deterioration was greater in the controls than the firemen for vital capacity, ratio of residual volume to total lung capacity, FEV1, FVC, peak expiratory flow (PEF), flow at 50% and 25% remaining vital capacity (V50 and V25 respectively), and airways resistance (Raw). With respect to PEF, V50, V25, and Raw the control subjects deteriorated more rapidly even than the smokers and ex-smokers among the firemen. Alveolar mixing efficiency (AME), a measure of small airways function, did not change significantly over the study period in any group. Non-smoking firemen had the highest mean value of AME, decreasing through ex-smokers, controls, and smokers. We conclude that these results show no evidence of chronic lung damage in West Sussex firemen; indeed, the firemen as a group show a lower rate of deterioration of lung function with age than do the control subjects. This is attributed to the selection of fit men for the service, continued physical training, and the regular use of breathing apparatus. PMID- 3342195 TI - Interactions of m-xylene and aspirin metabolism in man. AB - In a series of experiments to investigate interactions between industrial solvents and common medications the interaction between m-xylene and aspirin was studied. As both these substances are metabolised and excreted as glycine conjugates there would possibly be competition for this conjugation pathway. Five male volunteers were exposed on separate occasions to m-xylene by inhalation (100 ppm), aspirin (1500 mg) by mouth, and m-xylene and aspirin together under controlled conditions in an exposure chamber. Urine and blood samples were collected and analysed for m-xylene, aspirin, and their metabolites. The amounts of the major glycine conjugates produced from m-xylene (m-methylhippuric acid) and aspirin (salicyluric acid) were significantly reduced by about 50% when m xylene and aspirin were coadministered. There appears to be a mutual inhibition on the formation of the respective glycine conjugates. It is suggested that the inhibition is due to competition for either the enzymes, acyl-CoA synthetase, or glycine N-acylase. These findings have implications in the biological monitoring of workers exposed to m-xylene. PMID- 3342194 TI - Diverse manifestations of trichloroethylene. AB - Trichloroethylene, a solvent used in a variety of industrial settings for more than 60 years, has caused adverse health effects on the central and peripheral nervous system, the skin, liver, kidney, and heart. Three men have shown relatively unusual manifestations secondary to exposure to trichloroethylene in degreasing operations in the jewelry industry. Toxic encephalopathy, hepatitis, and carpal spasm occurred among young, healthy workers. Clinical and laboratory data, including measurement of urinary trichloroacetic acid concentrations, are presented. PMID- 3342196 TI - 2,5-Hexanedione excretion after occupational exposure to n-hexane. AB - The urinary excretion of the n-hexane metabolite 2,5-hexanedione (HD) was determined in four shoe factory workers during four workingdays that were preceded by four free days and followed by two free days. The correlation between excretion of HD and the n-hexane concentrations in the workroom air was evaluated. The air concentrations of n-hexane and those of acetone, toluene, and other organic solvents were monitored with charcoal tubes. All the urine from each worker was collected at freely chosen intervals during the experimental period and the following two free days. The samples were analysed by gas chromatography. The relative excretion of HD increased as the exposure to n hexane increased, although it seemed that HD accumulated progressively in the body at the highest n-hexane concentrations and at higher total solvent concentrations. PMID- 3342197 TI - Danger: children at work. PMID- 3342198 TI - Exposure to asbestos and the risk of gastrointestinal cancer: a reassessment. AB - In 1964 it was first reported that asbestos workers had a higher risk of gastrointestinal cancer. This notion has persisted despite several studies that have found no increased risk. The risks of gastrointestinal cancer to workers exposed to asbestos were reassessed, based on the results of published studies on 32 independent cohorts of asbestos workers. Not all studies provided risk estimates (SMRs) for all gastrointestinal sites (ICD codes 150-159). No consistent evidence was found to indicate that exposure to asbestos increases the risk of gastrointestinal cancer. Generally, the higher SMRs came from studies conducted in the United States or Canada and might reflect factors not related to exposure to asbestos. In studies in which asbestos exposed and non-asbestos exposed workers were evaluated the SMRs were not consistently higher for the group exposed to asbestos. There was no apparent dose response relation between accumulated asbestos dose and the risk of gastrointestinal cancer. It is concluded that there is no dose response relation between exposure to asbestos and risk of gastrointestinal cancer, and asbestos workers are not at an increased risk of gastrointestinal cancer. PMID- 3342199 TI - Pulmonary function in beryllium workers: assessment of exposure. AB - The inhalation of beryllium causes a serious lung disease characterised by pronounced radiographic and functional impairments and occurs in workers engaged in the extraction and manufacture of the metal. This paper describes the beryllium exposure levels and refining processes in a large beryllium factory operating since the 1930s. Lifetime beryllium exposure histories were estimated for the 309 workers present at a health survey conducted in 1977. Beryllium exposure levels in the plant were high for many years, with some estimated exposure levels in excess of 100 micrograms/m3. As late as 1975, there were exposures to beryllium above 10 micrograms/m3 in some jobs. After about 1977, the plant was in compliance with the permissible exposure limit of 2.0 micrograms/m3. The median cumulative exposure in this cohort was 65 micrograms/m3-years and the median duration of exposure was 17 years. From these data a series of exposure parameters, functions of the exposure histories that characterise biologically important dimensions of exposure were calculated for each worker. PMID- 3342200 TI - Increasing evidence of the rise of cancer in workers exposed to vinylchloride. AB - The results of a cancer mortality study among workers employed in the production of vinylchloride and polyvinylchloride between 1939 and 1977 suggest a significant increase in deaths from malignancies of the lymphatic and haemopoietic tissues. Mortality for tumours of the digestive organs, respiratory system, bone and connective tissues, brain, and skin are also greater than in the general population. There were no registered cases of liver angiosarcoma in the study cohort during the follow up period. The risk of cancer was highest among the workers exposed to concentrations of VC of 300 mg/m3 and more who had worked at the plant for 15 to 19 years. The relatively high number of leukaemias and lymphomas in the study group and the absence of liver angiosarcomas probably reflects specific carcinogenic action of different doses of vinylchloride. PMID- 3342201 TI - Cause specific mortality among employees engaged in the manufacture, formulation, or packaging of 2,4-dichlorophenoxyacetic acid and related salts. AB - Mortality is reported to the end of 1982 for 878 chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) at any time between 1945 and 1983. Observed mortality was compared with expected levels based on adjusted rates for United States white men and for other male employees from this manufacturing location who were not exposed to 2,4-D. Because of a recently reported increased incidence of astrocytomas in male rats fed the highest dose level of 2,4-D, special attention was given to deaths from brain neoplasms in the cohort. None was observed. The absence of an increased risk of brain cancer in people exposed to 2,4-D is supported by studies of other exposed populations and those studies are briefly reviewed. Moreover, in the present study, analyses by production area, duration of exposure, and cumulative dose showed no patterns suggestive of a causal association between 2,4-D exposure and any other particular cause of death. PMID- 3342202 TI - Combining results from several clinical trials. PMID- 3342204 TI - In utero meconium aspiration: an unpreventable cause of neonatal death. PMID- 3342203 TI - A purpose-designed cannula for transcervical chorion villus aspiration. PMID- 3342205 TI - Prolactin measurement in the investigation of infertility in women with a normal menstrual cycle. PMID- 3342206 TI - A randomized control study of oxytocin augmentation of labour. 1. Obstetric outcome. PMID- 3342207 TI - Magnetic resonance imaging (MRI) in obstetrics. I. Maternal anatomy. AB - We assessed the ability of magnetic resonance, a recently introduced imaging technique, to demonstrate the maternal anatomy in obstetrics. The signal intensity of different maternal tissues using T1 and T2 weighted sequences was examined. The bony pelvis is depicted with sufficient clarity to provide an alternative to conventional X-ray pelvimetry. The placenta and cervix have a distinctive appearance facilitating the diagnosis of placenta praevia. The unique demonstration of cervical morphology will offer the potential for investigation into the ill-understood conditions of cervical dystocia and cervical incompetence. PMID- 3342208 TI - Magnetic resonance imaging (MRI) in obstetrics. II. Fetal anatomy. AB - Magnetic resonance imaging (MRI) was performed in 36 patients at between 10 and 38 weeks gestation to determine the fetal anatomy that could be identified at different gestations. Fetal motion significantly degraded the image quality in the first and second trimesters, but in the final trimester fetal anatomy was clearly demonstrated. T2 weighted sequences showed the fetal brain and lungs to have a high signal intensity. Shorter TR leading to a T1 weighting gave better resolution of the overall anatomy. MRI has revealed the potential for assessment of lung maturity and the growth-retarded fetus. PMID- 3342209 TI - An analysis of uterine activity in spontaneous labour using a microcomputer. AB - A microcomputer was used to analyse uterine activity during spontaneous labour in 30 nulliparous and 30 parous patients. The intrauterine mean active pressure (MAP) in the nulliparous group was 1.51 kPa (SD 0.45) in the first stage and 2.71 kPa (SD 0.77) in the second stage. For the parous group, the MAP in the first stage was 1.22 kPa (SD 0.37) and in the second stage was 2.92 kPa (SD 0.98). A significant parity difference in MAP and contraction frequency was observed in the first stage but not in the second stage. Epidural analgesia did not appear to influence uterine activity in the first stage but was associated with a lower MAP, contraction frequency and intensity in the second stage. During the first stage, MAP increased by 21% in nulliparas and by 39% in multiparas. The rise in MAP was mainly due to an increase in contraction frequency. PMID- 3342210 TI - Doppler echocardiographic assessment of atrioventricular velocity waveforms in normal and small-for-gestational-age fetuses. AB - A prospective longitudinal study determined the physiological patterns of blood flow velocity waveforms in normal and in small-for-gestational-age (SGA) fetuses. Using a Pulsed Doppler Duplex system, 125 normally grown fetuses and 35 SGA fetuses were studied longitudinally at between 27 and 42 weeks gestation. In normal fetuses the ratio between the E velocity (early passive ventricular filling) and the A velocity (active ventricular filling during atrial contraction) increased progressively during pregnancy in both transmitral and transtricuspid waveforms, approaching 1 at term. In SGA fetuses, the E/A ratios did not increase during pregnancy and the values obtained were significantly lower than in normal fetuses. The ratio between the transtricuspid and transmitral mean temporal velocities remained almost constant throughout pregnancy in the normal fetuses with transtricuspid velocity slightly exceeding the transmitral velocity. On the other hand, in SGA fetuses the ratio between the mean temporal velocities was inversed with the transmitral velocity progressively greater than the transtricuspid velocity suggesting the existence of intracardiac haemodynamic changes in these fetuses. PMID- 3342211 TI - A study comparing transcervical with transabdominal chorionic villus sampling (CVS). AB - Chorionic villus sampling (CVS) was performed in 50 anaesthetized patients before therapeutic abortion by the transabdominal route and then by the transcervical route. The two methods of villus sampling were equally successful in obtaining villi but the transcervical method was significantly better at obtaining chorionic villi greater than 10 mg in weight (chi 2 13.92 P less than 0.001). Placental position did not affect villus recovery with either sampling method. PMID- 3342212 TI - Gestational diabetes and impaired glucose tolerance of pregnancy in Riyadh. AB - A total of 1088 pregnant women was screened for abnormalities in glucose metabolism at the initial antenatal visit; those with specific risk factors were screened again after 28 weeks gestation. In 210 (19.3%) plasma glucose measured 2 h after a 75 g glucose load was greater than or equal to 7.8 mmol/l (140 mg/dl). Follow-up glucose tolerance tests revealed an overall prevalence of abnormal tests of 10.3% (112 of 1088) according to the WHO criteria, of which 21 (1.9%) were diagnosed as gestational diabetes, and 91 (8.4%) as impaired glucose tolerance. This high prevalence was significantly related to age, parity and body mass index. Screening and diagnosis using criteria set by the WHO were found acceptable and are recommended to help resolve the international disagreement on diagnostic criteria of glucose metabolism abnormalities in pregnancy. PMID- 3342213 TI - Obesity and urinary incontinence in women. AB - In a series of 368 incontinent women who presented to our urodynamic clinic for assessment, 232 (63%) were diagnosed as having genuine stress incontinence, and 136 (27%) as having detrusor instability. Obesity (greater than 20% more than average weight for height and age) was significantly more common in women with genuine stress incontinence and detrusor instability than in the normal population. In those with detrusor instability the body mass index was found to increase with age and parity. In women with genuine stress incontinence the body mass index increased with age and the number of previous incontinence operations; it was higher in nulliparous than in parous women. There was no significant difference between obese and nonobese women in any of the urodynamic variables measured in the two incontinence groups. PMID- 3342214 TI - Why retrobulbar anaesthesia? PMID- 3342215 TI - Morphological observations on patients with presumed trichiasis. AB - The clinical findings in 116 patients with a provisional diagnosis of trichiasis are presented. In 69% a small degree of entropion producing lash-globe contact was detected. The term lid border entropion is proposed for this condition, which is recognised clinically by conjunctivalisation of the meibomian gland orifices and anterior placement of the mucocutaneous junction. These features were clearly demonstrated by electron microscopy of a biopsy specimen from one patient. An analysis of other causes of trichiasis is discussed and an attempt is made to clarify the terminology currently in use. PMID- 3342216 TI - Ocular quinine toxicity. AB - A case of ocular quinine toxicity is described which showed the typical acute visual loss and subsequent recovery. Vermiform motion of the pupil was noted 48 hours after overdose. This acute effect has not been reported before. Although acute systemic intoxication may respond to removal of quinine from the gut and circulation, there is no evidence that any treatment affects the visual prognosis. The action of quinine on the retina is unknown. We suggest it may block cholinergic neurotransmission in the inner synaptic layer. PMID- 3342217 TI - Tissue response to aqueous drainage in a functioning Molteno implant. AB - The tissue reaction to a functioning Molteno implant has been studied by light microscopy and by scanning and transmission electron microscopy. The material was obtained from an aphakic 83-year-old human eye which required enucleation because of intractable bullous keratopathy, despite well controlled intraocular pressure. The tissue response around the silicone rubber tube was that of simple fibroblastic activity. Around the implant, however, there was fibrous tissue in which necrotic cell debris was prominent. No significant inflammation was observed in this tissue, but the choroid beneath the implant showed a focal inflammatory cell infiltrate. The morphology suggests that the tissue around all surfaces of the implant (450 mm2) is exposed to aqueous, which seems to have a toxic effect on the encapsulating connective tissue. The changes seen in the tissue exposed to draining aqueous are similar to those described in experimental studies of the effect of aqueous on cell growth in tissue culture. PMID- 3342218 TI - Contrast sensitivity and acuity relationship in strabismic and anisometropic amblyopia. AB - The contrast sensitivity function (CSF) and visual acuity were determined in children and adults with unilateral amblyopia due to strabismus or anisometropia with central fixation. The preschool children were examined repeatedly during occlusion treatment. All amblyopes had CSF deficits. The CSF was characterised by its peak value (the maximal sensitivity, Smax, and the spatial frequency at which Smax occurs, Frmax) calculated by a single peak least-square regression method. The two amblyopic groups showed discrepancies in relationship of both Smax and Frmax versus visual acuity both initially and during treatment. The strabismic cases had a more marked visual acuity deficit in relation to the contrast sensitivity losses, whereas these parameters are affected similarly in anisometropic amblyopes. The relationship between recovery of visual acuity and CSF during the initial month of occlusion treatment was of prognostic significance for the outcome of visual acuity improvement. PMID- 3342219 TI - Grating and recognition acuities of young amblyopes. AB - The visual acuities of 36 young amblyopes were determined by (a) conventional recognition tests (near and distance) and (b) an adapted grating acuity card procedure. Considerable agreement between the estimates of acuity obtained with each method was demonstrated, which was generally less than, or equal to, the mean difference between adjacent Snellen lines (4.5 c deg-1). Estimates of grating acuity obtained with vertical gratings did not differ significantly from those obtained with horizontal gratings. There was no difference between the subjects' ability to detect the grating (acuity) and accurately to discriminate target orientation (horizontal or vertical). The results of the experiment are discussed in relation to previous findings of a discrepancy between grating and recognition acuities in amblyopia, and the clinical use of the acuity card procedure. PMID- 3342220 TI - Norrie's disease in an Asian family. AB - Norrie's disease, a congenital progressive oculo-acoustico-cerebral degenerative condition, is a sex linked recessive disorder. Previously described as atrophia oculi congeneti, it is associated with bilateral pseudotumour of the retina, lens, and corneal opacities, and phthisis bulbi. Some patients develop progressive deterioration of mental function and hearing. We report a Sri Lankan family with typical features of Norrie's disease. PMID- 3342221 TI - Childhood blindness in Jamaica. AB - Examinations were performed on the 108 blind Jamaican children (VA less than 6/60 in the better eye) in residential care. The congenital rubella syndrome (CRS) was the leading preventable cause of childhood blindness, accounting for 22% of children examined. Improvement of the rubella immunisation programme and the introduction of appropriate surgical procedures constitute recent attempts to combat childhood blindness. PMID- 3342222 TI - Automated morphometry of corneal endothelial cell: use of video camera and video tape recorder. AB - We developed an apparatus for automated morphometry of the corneal endothelium, which was photographed through a specular microscope connected to a video camera, and the images were stored on a video tape. The clearest stationary image was input into an image analyser to determine automatically the cell boundaries. Although human interaction is generally necessary, the mean time required to complete this procedure was about 13 minutes, based on the results of the 30 normal eyes, and the time needed for manual correction was about 4 minutes. The mean cell area obtained by this method correlated well (r = 0.9335) with that obtained by tracing the same images. This apparatus is clinically useful for immediately obtaining the mean cell area of corneal endothelium and will extend the application of specular microscopy to the routine clinical setting. PMID- 3342223 TI - Acute posterior multifocal placoid pigment epitheliopathy and sarcoidosis. AB - We report on a patient with acute posterior multifocal placoid pigment epitheliopathy and sarcoidosis. A review of the literature suggests that sarcoidosis may occur more commonly in this condition than previously suspected. PMID- 3342224 TI - Cranial nerve palsy following retrobulbar anaesthesia. PMID- 3342225 TI - Branch retinal arteriolar occlusion with chicken-pox. PMID- 3342226 TI - Activation of low Km hexokinases in purified hepatocytes by binding to mitochondria. AB - Hepatocytes were purified on a Percoll gradient. The cell membrane of these hepatocytes was disrupted by digitonin in the presence of albumin, glucose and physiological concentrations of monovalent and divalent cations. This treatment led to a separation between free and loosely structure-bound cytosolic enzymes which is not achieved by conventional subfractionation techniques. According to kinetic and immunological analyses, the free extractable cytosolic fraction contained high Km, hexokinase (glucokinase) and less than 10% of low Km hexokinases, while the hexokinase activity bound to the cell structures represented exclusively low Km isozymes. The total activity of the bound hexokinases was comparable to that observed in the supernate (approx. 1.0 U per g fresh weight). This activity decreased more than 10-fold upon desorption at higher digitonin concentrations. Such activation by binding, as well as inactivation by desorption, could also be demonstrated in intact hepatocytes correlated to different metabolic states, and also in vitro with isolated mitochondria and purified isozyme I. The binding of low Km hexokinases in hepatocytes was restricted to the mitochondrial fraction and there it was observed in the contact sites between the two mitochondrial boundary membranes. In view of these findings it appears that the binding-dissociation equilibrium of low Km hexokinases plays an important role in metabolic regulation of glucose uptake and glycogen synthesis in the liver and presumably in muscle. PMID- 3342227 TI - Thermodynamic bookkeeping when nucleotides bind. Applications of the theory of linked functions. AB - The thermodynamic theory of linked functions was used to determine the numbers of modifier ions involved when nucleotides dissociate. Nucleotide dissociation constants, obtained spectrophotometrically using Dowex-1 resin as a model system, were plotted on log/log paper with respect to the modifier concentrations. The slopes of the lines represent the net number of modifier molecules/ions involved in the dissociation. Varying numbers of nucleotides are bound to the resin because the resin capacity is determined by the total number of charges bound. The nucleotides bind to the resin at comparable diffusion-limited rates, irrespective of how tightly they bind. When ATP binds at pH 6.8, 4 chlorides, 4 formates, 2 succinates or 1.4 citrates are displaced, indicating that the fully charged (ATP4-) nucleotide binds. By comparing ATP, ADP and AMP it was possible to evaluate the contributions of the adenosine moiety and each phosphate to the binding. Between pH 2 and 3, where ATP has two negative charges, ATP binds largely as the trianion, displacing 2.7 chlorides and 0.7 protons. In the presence of 4 mM magnesium, 0.58 magnesiums facilitate the dissociation by chelating 58% of the liberated ATP. Calcium behaved similarly to magnesium but aluminum, at pH 6.8, promoted the binding of ATP as an (A1.ATP)3- complex with the concomitant liberation of three chloride ions. These experimental thermodynamic stoichiometries were found to be independent of the concentrations of the other modifiers present. Thermodynamic linkage stoichiometries can be evaluated from log K vs. log (modifier) plots when a direct determination of modifier binding is impossible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342228 TI - Modification of lipid phase behavior with membrane-bound cryoprotectants. AB - Several derivatives of cholesterol containing oxyethylene headgroups with and without a terminal galactose have been synthesized in order to examine the effects of immobilizing a cryoprotectant at a membrane surface. In this work, we have studied the ability of the triethoxycholesterol (TEC) and triethoxycholesterol galactose (TEC-Gal) derivatives to modulate the phase behavior of phosphatidylcholine and phosphatidylethanolamine membranes. Methods of fluorescence polarization, 31P-NMR and freeze-fracture electron microscopy were employed to monitor these changes in lipid phase behavior. Fluorescence polarization data demonstrated the ability of the derivatives to fluidize gel state and rigidify liquid-crystalline state phosphatidylcholines in a manner similar to that observed for cholesterol. Unlike cholesterol, however, the Tm of dipalmitoylphosphatidylcholine (DPPC) was reduced in a concentration-dependent manner with each of the derivatives. Freeze-fracture electron microscopy and 31P NMR of DOPE dispersions indicate an increase in the lamellar to hexagonal phase transition temperature on the order of 10-20 C degrees above room temperature for mixtures with 20 mol% of the derivatives. These results are discussed in terms of the properties exhibited by compounds such as carbohydrates, which are known to serve as cryoprotectants for synthetic and biological membranes. PMID- 3342229 TI - Transbilayer diffusion of phospholipids: dependence on headgroup structure and acyl chain length. AB - The kinetics and thermodynamics of the transmembrane movement (flip-flop) of fluorescent analogs of phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were investigated to determine the contributions of headgroup composition and acyl chain length to phospholipid flip-flop. The phospholipid derivatives containing n-octanoic, n decanoic or n-dodecanoic acid in the sn-1 position and 9-(1-pyrenyl)nonanoic acid in the sn-2 position were incorporated at 3 mol% into sonicated single-bilayer vesicles of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC). The kinetics of diffusion of the pyrene-labeled phospholipids from the outer and inner monolayers of the host vesicles to a large pool of POPC acceptor vesicles were monitored by the time-dependent decrease of pyrene excimer fluorescence. The observed kinetics of transfer were biexponential, with a fast component due to the spontaneous transfer of pyrenyl phospholipids in the outer monolayer of labeled vesicles and a slower component due to diffusion of pyrenyl phospholipid from the inner monolayer of the same vesicles. Intervesicular transfer rates decreased approx. 8-fold for every two carbons added to the first acyl chain. Correspondingly, the free energy of activation for transfer increased approx. 1.3 kcal/mol. With the exception of PE, the intervesicular transfer rates for the different headgroups within a homologous series were nearly the same, with the PC derivative being the fastest. Transfer rates for the PE derivatives were 5-to 7 fold slower than the rates observed for PC. Phospholipid flip-flop, in contrast, was strongly dependent on headgroup composition with a smaller dependence on acyl chain length. At pH 7.4, flip-flop rates increased in the order PC less than PG less than PA less than PE, where the rates for PE were at least 10-times greater than those of the homologous PC derivative. Activation energies for flip-flop were large, and ranged from 38 kcal/mol for the longest acyl chain derivative of PC to 25 kcal/mol for the PE derivatives. Titration of the PA headgroup at pH 4.0 produced an approx. 500-fold increase in the flip-flop rate of PA, while the activation energy decreased 10 kcal/mol. Increasing acyl chain length reduced phospholipid flip-flop rates, with the greatest change observed for the PC analogs, which exhibited an approx. 2-fold decrease in flip-flop rate for every two methylene carbons added to the acyl chain at the sn-1 position.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3342230 TI - Kinetic evidence for heterogeneity in Na+-D-glucose cotransport systems in the normal human fetal small intestine. AB - Zero-trans kinetic studies of Na+-D-glucose cotransport have been performed under voltage-clamped conditions in brush-border membrane vesicles isolated from both jejunum and ileum of 17-20-week-old normal human fetuses. Varying glucose concentrations in the incubation medium led to curvilinear Eadie-Hofstee plots in the jejunum only, thus suggesting the presence of both high-affinity, low capacity (Km 0.37 mM; Vmax 8.3 nmol/min per mg protein) and low-affinity, high capacity (Km 4.2 mM; Vmax 30.9 nmol/min per mg protein) systems in the proximal small intestine, and of a single carrier (Km 1.2 mM; Vmax 4.9 nmol/min per mg protein) in the distal small intestine. Sodium activation curves provide further evidence for heterogeneity in glucose transport systems in the fetal small intestine: Hill coefficients of 2 and 1 were found for the jejunal high-affinity and ileal systems, and for the jejunal low-affinity system, respectively. It is concluded that there is early differentiation of a functional heterogeneity in glucose transport capacity along the human fetal small intestine. PMID- 3342231 TI - Comparative assessment of the resistance of the unstirred water layer to solute transport between two different intestinal perfusion systems. AB - The resistance of the unstirred water layer to solute transport was estimated in two different intestinal single-pass perfusion systems for a comparative study, using D-glucose as a model compound. One is a well established perfusion system in anesthetized rats as a standard (system A). The other is the one in unanesthetized rats for comparison (system B). It was demonstrated that in system B as well as in system A the resistance of the unstirred water layer to D-glucose transport should be taken into account and this resistance, accordingly, the effective thickness of the unstirred water layer (delta) which is assumed to be in proportion to its resistance, could be described as a function of the perfusion rate by using a film model. The delta decreased with increasing perfusion rate and was larger in system A than in system B at each perfusion rate; 785 microns in system A versus 319 microns in system B at the perfusion rate of 0.16 ml/min and 337 microns versus 184 micron at that of 2.95 ml/min. Thus in system B the effective thickness, accordingly, the resistance, of the unstirred water layer was reduced to about 50% of that in system A, but the resistance of the unstirred water layer could still account for 85% of the total resistance at the maximum as far as D-glucose absorption was concerned, while 93% in system A. These results suggest that, compared with perfusion experiments in anesthetized rats (system A), the resistance of the unstirred water layer is reduced but cannot be left out of consideration even if perfusion experiments are performed in unanesthetized rats (system B). And the lower resistance of the unstirred water layer in system B was attributed to a turbulent flow in contrary to a laminar flow in system A. PMID- 3342232 TI - Solubilization and assay of phospholipase A2 activity from rat jejunal brush border membranes. AB - The phospholipase activity of rat jejunal brush-border membranes was examined in the presence of several solubilizing agents, by measuring the hydrolysis of endogenous membrane phospholipids, as well as the hydrolysis of exogenous, radiolabelled substrates. Enzyme activity was highly stimulated by dispersion in 1% solutions of bile salts, or in a synthetic, bile-salt derivative, 3-[(3 cholamidopropyl)dimethylammonio]propanesulphonate (CHAPS). Under these conditions the endogenous membrane phospholipids were largely degraded to free fatty acids and water-soluble phosphate. In the presence of 1% CHAPS, hydrolysis of exogenous phosphatidylcholine was shown to be due to an initial phospholipase A2-type attack followed by a subsequent lysophospholipase-type attack. These activities co-purified with the brush-border membrane. Maximal phospholipase A2 hydrolysis occurred at an alkaline pH of 8-11, with bile-salt detergents present at greater than their critical micellar concentrations. Hydrolysis was completely divalent ion independent. Phospholipase A2 activity was not stimulated by 50% diethyl ether or ethanol, or in the presence of 1% solutions of Triton X-100, Zwittergent 3-12, sodium dodecyl sulphate, or n-octylglucoside. Stimulation of phospholipase activity by detergents was not related to their effectiveness at solubilizing the membrane proteins. When assayed individually phosphatidylcholine and lysophosphatidylcholine were each hydrolyzed (at the sn-2 and sn-1 positions, respectively) at a rate of approximately 125 nmol/mg protein per min. When assayed together, the two substrates appeared to compete for the same active site over a wide range of concentrations. It was concluded that the brush-border membrane contains an integral membrane protein with phospholipase A2 and lysophospholipase activities, which is specifically stimulated by bile salts and bile salt-like detergents. PMID- 3342233 TI - Temperature dependence of glucose transport in erythrocytes from normal and alloxan-diabetic rats. AB - Alloxan diabetes increased 3-O-methylglucose transport rates in rat red blood cells (RBC) at temperatures below 30 degrees C and decreased them above 30 degrees C. Preincubation of RBC from control rats with 20 mM glucose, 3-O methylglucose, 2-deoxyglucose or xylose greatly elevated transport at 14 degrees C by increasing Vmax. The effect was slight at 40 degrees C. Preincubation with glucose or deoxyglucose alone caused a 50% depression of transport rates at 40 degrees C as a result of a rise in the Km, which is similar to findings in cells from alloxan-diabetic rats. Measurement of intracellular glucose metabolites suggested inhibition of glycolysis in cells from diabetic rats and a positive correlation between the level of intracellular hexose monophosphates and transport inhibition. Membrane fatty-acid and cholesterol composition and membrane lipid-ordering as monitored by electron paramagnetic resonance were not altered by alloxan diabetes. It is concluded that intracellular sugar and sugar metabolism alter the temperature dependence of glucose transport kinetics. Glucose metabolism can feed back to inhibit transport by increasing the transport Km at physiological temperatures only. PMID- 3342234 TI - Temperature, pressure and cholesterol effects on bilayer fluidity; a comparison of pyrene excimer/monomer ratios with the steady-state fluorescence polarization of diphenylhexatriene in liposomes and microsomes. AB - Pyrene excimer/monomer (E/M) ratios have been compared with the steady-state fluorescence polarization (P) of diphenylhexatriene (DPH) in multilamellar liposomes of dilaurylphosphatidylcholine and rat liver microsomes. The purpose was to use the well-understood properties of DPH to reveal the nature of bilayer fluidity which pyrene manifests as an E/M ratio. Reducing the temperature (from 37 degrees C to 8 degrees C), increasing the hydrostatic pressure (from 0.1 to 70 MPa), and, in liposomes, cholesterol enrichment (up to 0.30 mole fraction) separately decreased the E/M ratios and increased P. The pyrene membrane/buffer partition coefficient was affected by temperature but not by pressure, and in the case of cholesterol enrichment, it was assumed to be unaffected. Plots of P as a function of the E/M ratio showed the two to be closely correlated (r = 0.99 in liposomes and 0.96 in microsomes), independent of the treatment used to reduce fluidity. The apparent activation volume and enthalpy for excimer formation was calculated and compared with published data. Pyrene E/M ratios probably reflect the intermolecular volume (fluidity) of the outer region of the bilayer, which is reduced by a decrease in temperature and an increase in pressure and cholesterol. DPH reports the bilayer interior, which is similarly ordered by the experimental treatments. The regional distinction between the two probes, however, accounts for the divergence of E/M ratios and P, which has been reported in membranes enriched with fluidizing fatty acids. PMID- 3342235 TI - Immobilization of phospholipid vesicles and protein-lipid vesicles containing red cell membrane proteins on octyl derivatives of large-pore gels. AB - For improved immobilization of phospholipid vesicles and protein-lipid vesicles (cf. Sandberg, M., Lundahl, P., Greijer, E. and Belew, M. (1987) Biochim. Biophys. Acta 924, 185-192) and for chromatographic experiments with vesicles containing membrane protein, we have prepared octyl sulfide derivatives of the large-pore gels Sephacryl S-1000 and Sepharose 2B with ligand concentrations up to 14 and 5 mumol/ml gel, respectively. The Sephacryl derivatives allowed higher flow rates, gave higher rates of adsorption and showed equally high or higher capacities than the Sepharose adsorbents. 'Small', 'medium' and 'large' vesicles of radii approx. 20, 50 and 100 nm showed distribution coefficients on Sephacryl S-1000 of 0.7, 0.5 and 0.05, respectively and could be immobilized on octyl sulfide-Sephacryl S-1000 in amounts corresponding to 110, 40 and 20 mumol of phospholipids per ml gel, respectively. 'Small' vesicles became absorbed onto this gel at a rate of 1.5 mumol of phospholipids per min per ml gel until 60 mumol of phospholipids had become immobilized, whereas the initial adsorption rate was about 0.4 mumol.min-1.ml-1 on octyl sulfide-Sepharose 4B (see reference above) and on octyl sulfide-Sepharose 2B. Lower ligand concentrations gave lower capacities for 'small' vesicles. When vesicles entrapping calcein were immobilized on octyl sulfide-Sephacryl S-1000 some calcein was released during the adsorption process. For 'small' and 'medium' vesicles, respectively, the leakage was 75 and 25% at a ligand concentration of 14 mumol/ml but only 3 and 2% at 5 mumol/ml. The internal volumes of immobilized 'small' and 'medium' vesicles were estimated at 0.97 and 2.9 microliters per mumol of phospholipid by determination of entrapped calcein, which could indicate vesicle radii 20 and 50 nm, respectively. The total volumes of immobilized 'medium' lipid vesicles and 'medium' protein-lipid vesicles containing integral membrane proteins from human red cells, were estimated at 2.9 and 2.0 microliters/mumol, respectively, by chromatography of D- and L-[14C]glucose and calcein on the octyl sulfide Sephacryl S-1000 column before and after immobilization. These volumes are roughly consistent with the internal volume of the vesicles. A zone of D-glucose eluted 90 microliters later than a zone of L-glucose on a 4- or 5-ml column of octyl sulfide-Sephacryl S-1000 with immobilized 'medium' protein-lipid vesicles containing the glucose transporter from human red cells, probably since part of the internal vesicle volume was accessible to the D-glucose but not to the L glucose. This indicates that the glucose transporter was active in the immobilized vesicles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3342236 TI - Role of monocarboxylic acid transport in intracellular pH regulation of isolated proximal cells. AB - Isolated proximal cells were prepared from rabbit kidney cortex by mechanical dissociation. The intracytoplasmic pH (pHi) was measured in HCO3(-)-free media (external pH (pHe), 7.3) using the fluorescent dye 2,7-biscarboxyethyl-5,6 carboxyfluorescein (BCECF). Cells were acid-loaded by the nigericin technique. Addition of 70 mM Na+ to the cells caused a rapid pHi recovery, which was blocked by 0.5 mM amiloride. When the cells were exposed to 5 mM sodium butyrate in the presence of 1 mM amiloride, the H+ efflux was significantly increased and followed Michaelis-Menten kinetics. Increasing pHe from 6.4 to 7.6 at a constant pHi of 6.4 enhanced the butyrate activation of the H+ efflux. Increasing pHi from 6.5 to 7.2 at a constant pHe of 7.2 reduced the butyrate effect. 22Na uptake experiments in the presence of 1 mM amiloride showed that 1.5 mM butyrate increased the Na+ flux in the proximal cells (pHi 7.10). The efficiency of monocarboxylic anions in promoting a pHi recovery increased with the length of their straight chain (acetate less than propionate less than butyrate less than valerate). The data show that when the Na+/H+ antiporter is blocked, the proximal cells can regulate their pHi by a Na+-coupled absorption of butyrate followed by non-ionic diffusion of butyric acid out of the cell and probably also by OH- influx by means of the OH-/anion exchanger. PMID- 3342237 TI - Asymmetric distribution of gangliosides in rat renal brush-border and basolateral membranes. AB - Highly enriched brush-border and basolateral membranes isolated from rat renal cortex were used to study the distribution of endogenous gangliosides in the two distinct plasma membrane domains of epithelial cells. These two membrane domains differed in their glycolipid composition. The basolateral membranes contained more of both neutral and acidic glycolipids, expressed on a protein basis. In both membranes, the neutral glycolipids corresponding to mono-, di-, tri- and tetraglycosylceramides were present. The basolateral membranes contained more diglycosylceramide than the brush-border membranes. The major gangliosides found were GM4, GM3, and GD3 with minor amounts of GM1 and GD1a. The latter were identified and quantified by sensitive iodinated cholera toxin binding assays. When the distribution of individual gangliosides was calculated as a percent of total gangliosides, the brush-border membranes were enriched with GM3, GM1 and GD1a compared to the basolateral membranes, which were enriched with GD3 and GM4. The observation of a distinct distribution of glycolipids between brush-border and basolateral membranes of the same epithelial cell suggests that there may be a specific sorting and insertion process for epithelial plasma membrane glycolipids. In turn, asymmetric glycolipid biogenesis may reflect differences in glycolipid function between the two domains of the epithelial plasma membrane. PMID- 3342238 TI - Changes in the surface charge properties of isolated cardiac sarcolemmal vesicles measured by light scattering. I. Characteristics of rat and canine preparations. AB - The cation-binding characteristics of isolated sarcolemmal vesicles from rat and canine cardiac muscle cells were investigated. To help elucidate the molecular properties involved in these interactions the cation-induced aggregation behavior of rat and canine cardiac sarcolemmal vesicles, sonicated unilamellar vesicles (SUVs) made from sarcolemmal lipid extracts, and SUVs generated from combinations of synthetic lipids similar to those found in the sarcolemmal membrane, as well as mitochondrial and sarcoplasmic reticulum enriched membrane fractions were examined. Our results indicate that cations, such as Ca2+, to indeed bind to the sarcolemmal membrane surface. They also suggest that two (or more) interacting sites are involved in the Ca2+-induced aggregation of the isolated sarcolemmal vesicles, and that sarcolemmal lipid components could be the primary binding sites. The modulating (secondary) sites on the other hand may be protein or carbohydrate in nature, or require specific lipid organizational properties. Finally, the results indicate that the interactions of cations, such as Ca2+, with the sarcolemmal surface are species specific, with the sarcolemmal membranes of both rat and canine preparations having different physico-chemical properties. PMID- 3342239 TI - Characterization of a cDNA for human glutathione-insulin transhydrogenase (protein-disulfide isomerase/oxidoreductase). AB - A human liver cDNA expression library in lambda-phage gt11 was screened with monoclonal antibodies to rat liver protein-disulfide isomerase/oxidoreductase (EC 5.3.4.1/1.8.4.2), also known as glutathione-insulin transhydrogenase (GIT). The nucleotide sequence of the largest cDNA insert (hgit-1) was determined. It contained approx. 1500 basepairs, representing an estimated 65% of the glutathione-insulin transhydrogenase message. The amino-acid sequence deduced from this cDNA insert contains a 7-amino-acid long polypeptide determined by sequencing the active-site fragment isolated from the rat GIT protein. A comparison of the nucleotide sequence of hgit-1 and a previously reported nucleotide sequence of rat glutathione-insulin transhydrogenase cDNA shows that the human hgit-1 clone corresponds to the middle of the transhydrogenase message at amino-acid residue number 275 of the rat protein, and codes for 206 amino-acid residues, including one of the two active-site regions of glutathione-insulin transhydrogenase, a stop codon (TAA), a long 3'-noncoding region of over 800 bases, a polyadenylation signal (AATAA), and a 29 base poly(A) tail. There exists high homology between the human and rat enzymes (94% in the overall amino-acid sequence, with 100% in the active site region and 81% in the nucleotide sequence within the coding portion of hgit-1). As with the rat enzyme, the human enzyme shows some identity with another dithiol-disulfide-exchange protein, Escherichia coli thioredoxin. Like rat cDNA, the human hgit-1 cDNA hybridized to rat mRNA of 2500 bases on a Northern blot. The relative quantitative abundance of GIT mRNA in nine rat tissues studied using hgit-1 as a hybridization probe was found to be in the same order as previously found with the rat cDNA. Thus, the above studies indicate that glutathione-insulin transhydrogenase is a highly conserved protein and that the human hgit-1 cDNA is suitable for use as a probe for further studies on gene regulation of this enzyme. PMID- 3342240 TI - Structures and expression of mRNAs coding for major plasma proteins of Bombyx mori. AB - A group of structurally related proteins, referred to as '30K proteins', accumulate in a stage-dependent fashion in the larval hemolymph of the silkworm, Bombyx mori. To investigate the regulatory mechanisms of the 30K protein biosynthesis in the fat body, mRNA sequences coding for these plasma proteins were cloned and their structures and expression during the larval development were studied. Five plasmid clones, each bearing a distinct mRNA sequence coding for the 30K protein component, were isolated from a cDNA library constructed from the fat body poly(A)RNA of the mid-fifth instar larvae. These clones were remarkably similar to each other with respect to both the nucleotide and the amino-acid sequences. Each clone carried an open reading frame for amino-acid residues 251 to 264, with a typical signal sequence for transmembrane secretion at the deduced amino-terminal domain. Northern blot hybridization provided evidence that the developmental change in the amount of 30K protein mRNAs in the fat body reflects well that of the hemolymph concentration of 30K proteins, indicating that the biosynthesis of 30K proteins is developmentally regulated at a transcriptional or post-transcriptional level in the fat body. PMID- 3342241 TI - Purification of duck growth hormone and cloning of the complementary DNA. AB - Duck growth hormone (GH) was isolated and purified from duck pituitaries by salt precipitation and HPLC on reverse-phase C18 columns. The duck GH was homogeneous as shown by SDS-polyacrylamide gel electrophoresis with a molecular weight of 22,000. The cDNA was synthesized and cloned in Escherichia coli using EcoRI linkers and pBR322 as vector. The positive clones were selected and sequenced. The full-length duck GH cDNA contains 820 nucleotide pairs with an open reading frame coding for the precursor form duck GH of 216 amino-acid residues. The partial amino-acid sequence from the protein completely agrees with that derived from the cDNA, with Phe as the first residue in mature duck GH preceded by a 27 residue hydrophobic signal peptide. The duck GH is almost completely homologous to the chicken GH, with only three conservative substitutions (Ser for Thr, His for Tyr and Lys for Arg) and one deletion (Ala) in the duck GH sequence. Comparison of amino-acid sequence of duck GH with that of various species reveals 56%, 73% and 40% homologies with GHs of human, rat and salmon, respectively. PMID- 3342242 TI - Purification and properties of aspartate transcarbamylase from Mycobacterium smegmatis. AB - Aspartate transcarbamylase (carbamoyl-phosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) has been purified from Mycobacterium smegmatis TMC 1546 using streptomycin sulphate precipitation, ammonium sulphate precipitation, DE-52 chromatography, second ammonium sulphate precipitation, Sephadex G-200 gel filtration, and aspartate-linked CNBr-activated Sepharose 4B affinity chromatography in successive order. The enzyme was purified 231.6-fold, and the preparation was found to be homogeneous on column chromatography and polyacrylamide gel electrophoresis. The purified enzyme had a molecular weight of 246,000 and was composed of two asymmetrical subunits. The kinetic and regulatory properties of aspartate transcarbamylase from M. smegmatis were also studied. The enzyme was found to be an allosteric in nature with carbamyl phosphate showing positive cooperativity and UMP exhibiting a negative cooperativity. CTP was found to be the most potent inhibitor among nucleotides. Phosphate acted as a non competitive product inhibitor with respect to aspartate. Succinate and maleate exerted a competitive inhibition when aspartate was the variable substrate. PMID- 3342243 TI - Nucleotide binding and affinity labelling support the existence of the phosphate binding subsite p2 in bovine pancreatic ribonuclease A. AB - When the reaction of bovine pancreatic ribonuclease A with 6-chloropurine riboside 5'-monophosphate was carried out in the presence of several natural mononucleotides, a decrease of 25-75% was found in the amount of the reaction product derivative II (the main product of the reaction which has the nucleotide label at the alpha-NH2 group of Lys-1). The efficiency of inhibition followed the order 3'-AMP greater than 5'CMP approximately equal to 5'AMP greater than 3'CMP. Previous studies indicate that this order reflects the extent of occupancy of p2, a phosphate-binding subsite adjacent to the catalytic centre. This finding suggests that derivative II is the result of affinity labelling and that the phosphate group of the halogenated nucleotide binds to p2 before the reaction takes place. The dissociation constants and stoichiometry of the interaction between native enzyme, derivative II and derivative E (homologous to derivative II, but labelled with a nucleoside instead of a nucleotide) with 3'AMP and 5'AMP at several pH values were also determined. Although in general one strong binding site was found, no strong binding occurs between 3'AMP and derivative II. It is concluded that the phosphate of the label occupies the same site p2, as the phosphate of 3'AMP. Finally, the pH dependence for the binding of 3'AMP and 5'AMP to RNAase A indicates that they bind to different protein groups. The results presented support the structure of the active site of ribonuclease A postulated previously (Pares, X., Llorens, R., Arus, C. and Cuchillo, C.M. (1980) Eur. J. Biochem. 105, 571-579). PMID- 3342244 TI - The effect of divalent cations on the interaction between calf spleen profilin and different actins. AB - The interaction between calf spleen profilin and actin depends critically on the status of the C-terminus of the actin, and in the case of profilin, the C terminus is of great importance for the physiochemical behaviour of the protein. Both proteins easily lose their C-terminal amino acids during the preparation, and special care has to be taken to ensure the isolation of the proteins in the intact form. Another factor that may seriously influence the study of the interaction of profilin with actin is the presence of varying amounts of an activity that causes an apparent stabilization of the complex even at later stages of its purification. We have found conditions for the isolation of intact profilin and actin, and studied the interaction between the two proteins, including the determination of the Kdiss for the complex formed under various ionic conditions. The complex formed between profilin and actin from calf spleen was found to be significantly stronger (Kdiss less than or equal to 10(-8) M in 50 mM KCl, and Kdiss = 4.10(-7) M in 50 mM KCl, 1 mM MgCl2) than that formed between profilin and muscle alpha-actin (Kdiss = 10(-6) M in 50 mM KCl, +/- 1 mM MgCl2). The profilactin complex formed in the mammalian system was stronger than the complex formed between Acanthamoeba actin and the profilin-like protein isolated from this organism. Analysis of the formation of the calf spleen complex in the presence of varying concentrations of divalent cations gave evidence for the presence of a high-affinity divalent-cation-binding site on the spleen actin (beta, gamma) which appears to regulate the interaction with profilin. PMID- 3342246 TI - Hydrogen transfer by NADPH-dependent reductases in elongation of very-long-chain saturated and polyunsaturated fatty-acyl-CoA in swine cerebral microsomes. AB - The hydrogen transfer from NADPH was studied in the elongation of arachidoyl-CoA (20:0-CoA) and arachidonoyl-CoA (20:4-CoA) in swine cerebral microsomes. Previously, we showed that four deuterium atoms (2H) were transferred stereospecifically from (4S)-[4-2H1]NADPH in the elongation of 20:0-CoA to 24:0 (Yoshida, S., Takeshita, M. and Kawaguchi, A. (1984) Biochem. Biophys. Res. Commun. 124, 322-328), and that three deuterium atoms were transferred from 2H2O in the elongation of 20:4-CoA to 22:4. The deuteride transfer from (4S)-[4 2H1]NADPH was observed in the elongation of 20:4-CoA to 24:4, by the technique of mass fragmentography using the chemical ionization method, and, in this case, two 2H were transferred to 24:4. No deuteride was transferred from (4R)-[4-2H1]NADPH in the elongation of 20:0-CoA and 20:4-CoA. Moreover, the condensation product (3 keto-fatty-acyl-CoA) which was formed in the elongation without NADPH could be reduced by the addition of NADPH and sodium hydrosulfite, for the elongation of 16:0-CoA and 20:4-CoA, while the condensation product from 20:0-CoA could be reduced only by NADPH, but not by hydrosulfite. The hydrosulfite did not produce the final elongation products from 20:0-CoA, 16:0-CoA or 20:4-CoA. These results suggested that the hydride was transferred from NADPH stereospecifically only in the elongation of 20:0-CoA in the step of 3-ketoacyl-CoA reduction by the reductase which might be different from that for the elongation of 16:0-CoA and 20:4-CoA in which the proton exchange might occur via a water proton in the reduction of 3-ketoacyl-CoA. Accordingly, the hydride transfer might occur from NADPH in the step of 2,3-enoyl reduction in the elongation of 20:0-, 16:0- and 20:4-CoA. PMID- 3342245 TI - A fluorescent sterol probe study of human serum low-density lipoproteins. AB - The fluorescent sterol probe, ergosta-5,7,9,(11),22-tetraen-3 beta-ol (dehydroergosterol), was utilized as a cholesterol analog to label human serum low-density lipoproteins (LDL). Quenching of dehydroergosterol fluorescence by KI indicated that most of the fluorophore was either buried within the outer phospholipid monolayer of LDL or within the neutral lipid core of LDL. The steady state anisotropy of dehydroergosterol in LDL detected the cholesteric core phase transition near 30 degrees C. Fluorescence lifetime decays for dehydroergosterol contained two components, both below and above the cholesteric phase transition, with the major lifetime component near 1 ns. Neither lifetime component underwent a detectable change in duration at the core phase transition temperature. Time correlated fluorescence anisotropy decays of dehydroergosterol indicated a single rotational correlation time near 1.7 ns, which was unaffected by the core phase transition. Time-correlated anisotropy decays also suggested hindered rotation of dehydroergosterol in LDL. These results indicate that unesterified cholesterol is primarily located in the outer phospholipid monolayer of LDL, with the majority of cholesterol not in direct contact with the aqueous phase. PMID- 3342247 TI - Studies on lipid peroxidation in rat liver nuclei and isolated nuclear membranes. AB - Non-enzymatic and enzymatically-driven lipid peroxidation processes were studied in rat liver nuclei and isolated nuclear membranes, by evaluating the formation of thiobarbituric acid-chromophore, free malondialdehyde, lipofuscin-like pigments, and the degradation of polyunsaturated fatty acids of the nuclear membrane lipids. The results obtained show that: (1) both non-enzymatic and enzymatically driven lipid peroxidation processes are operative in cell nuclei and isolated nuclear membranes; (2) only for isolated nuclear membranes, a good qualitative and up to a great extent quantitative correlation between malondialdehyde and lipofuscin-like pigment formation was obtained; (3) there is a qualitative but not quantitative correlation between malondialdehyde formation and polyunsaturated fatty acid degradation; (4) lipid peroxidation processes in isolated nuclear membranes and intact nuclei have an essentially identical kinetic behaviour. No statistical differences in the relative increases in the concentrations of malondialdehyde and lipofuscin-like pigments or in the degradation of polyunsaturated fatty acids were obtained, when the two systems were compared, except in the presence of NADPH-ADP-Fe3+, which induced a significantly larger degradation of polyunsaturated fatty acids in isolated nuclear membranes than in intact nuclei, and (5) no malondialdehyde-DNA fluorescent adduct formation was observed in any of the experimental groups studied, as inferred from the characteristics of the fluorescent spectra of lipofuscin-like pigments extracted from incubated nuclear preparations. PMID- 3342248 TI - Regulatory aspects of mitochondrial phospholipase A2: correlation of hydrolysis rates with substrate configuration as evidenced by 31P-NMR. AB - The influence of variation of the phospholipid composition in model membranes composed of phosphatidylcholine and phosphatidylethanolamine on the hydrolysis of these phospholipids by rat liver mitochondrial phospholipase A2 was investigated. With the pure phospholipids, phosphatidylethanolamine was hydrolyzed over 30 times faster than phosphatidylcholine. Upon increasing the mole percentage of phosphatidylethanolamine in mixtures, a gradual, though non-linear, increase in the initial rate of hydrolysis of this phospholipid was observed. By contrast, phosphatidylcholine hydrolysis remained constant up to about 50 mol% phosphatidylethanolamine, whereafter a sudden fall-off of activity was observed. This drop in the hydrolysis rate coincided with a transition of the phospholipid structure from bilayer to an as yet unidentified organization characterized by an isotropic signal in the 31P-NMR spectra recorded in the presence of Ca2+. The occurrence of this phase was clearly dependent on Ca2+, since mixtures with identical composition in the absence of Ca2+ remained largely in bilayer configuration. That the structure adopted by phospholipids is of importance for their susceptibility to attack by this intracellular phospholipase A2 became evident also in studies with the single phospholipids in the absence or presence of Triton X-100 above the critical micellar concentration. While phosphatidylcholine hydrolysis was inhibited in mixed micelles as compared to its bilayer organization, the hydrolysis of phosphatidylethanolamine in mixed micelles was 3-fold that in the hexagonal HII phase. PMID- 3342249 TI - Characterization of very-low-density lipoproteins isolated from baboons, and fractionated using heparin-Sepharose chromatography. AB - Plasma very-low-density lipoproteins (VLDL) (d less than 1.006 g/ml) were purified from baboons by repeated ultracentrifugation. The weight composition of VLDL purified from these animals was 59% triacylglycerol, 17% phospholipid, 13% cholesterol plus cholesteryl esters, and 11% protein. When purified VLDL was fractionated using heparin-Sepharose chromatography, an average of 33% of the total recovered proteins were unbound in a saline solution, and 67% (range, 31 to 92%) were bound by the column, but could be eluted with 3 M NaCl. Recoveries of starting protein and the major classes of lipids in the two fractions were 70 80%. The two fractions differed in both apolipoprotein and lipid compositions. Analysis of sodium dodecyl sulfate-treated apolipoproteins using 3-21.5% acrylamide gradient gel electrophoresis indicated that both VLDL fractions contained apolipoprotein B, but only the bound fraction possessed significant amounts of apolipoprotein E. On a weight percent basis, the apolipoprotein-E-rich (bound) VLDL fraction contained significantly more cholesterol and cholesteryl esters (P less than 0.001) and less phospholipids (P less than 0.005) compared to the apolipoprotein E-poor (unbound) VLDL. Apolipoprotein-E-poor VLDL had shorter retention times than E-rich VLDL upon gel filtration chromatography, suggesting a larger size. There was no significant correlation between plasma levels of apolipoprotein-E-poor VLDL and levels of apolipoprotein B. These results demonstrate that baboons possess VLDL which can be separated into apolipoprotein E-poor and E-rich fractions and these fractions differ in protein and lipid composition and in size. PMID- 3342251 TI - A new human pathology with visceral accumulation of long-chain n-alkanes; tissue distribution of the stored compounds and pathophysiological hypotheses. AB - This report deals with a new human disorder characterized by the accumulation of plant long-chain n-alkanes in viscera of a human patient. Lipid analysis of tissues from an adult male after sudden death (affected with diffuse visceral granuloma containing lipophilic crystallized material) showed the presence of abnormal compounds identified as long-chain n-alkanes with 29 (n-nonacosane), 31 (n-hentriacontane) and 33 carbons (n-tritriacontane). Study of n-alkane distribution in patient tissues showed a major accumulation in lumbo-aortic lymph nodes, adrenal glands, lung (the highest levels were found in lung granulomas) and liver; significantly lower amounts were detected in myocardium and kidney, whereas no detectable level was found in brain. On the basis of the structural composition and of the tissue distribution of the accumulated n-alkanes, their dietary (plant) origin and the pathophysiological mechanism of the storage are discussed. PMID- 3342250 TI - Acyl-CoA oxidase activity and peroxisomal fatty acid oxidation in rat tissues. AB - Acyl-CoA oxidase, the first enzyme of the peroxisomal beta-oxidation, was proved to be rate-limiting for this process in homogenates of rat liver, kidney, adrenal gland, heart and skeletal muscle. Acyl-CoA oxidase activity, based on H2O2 dependent leuko-dichlorofluorescein oxidation in tissue extract, was compared with radiochemically assayed peroxisomal beta-oxidation rates. Dichlorofluorescein production was a valid measure of peroxisomal fatty acid oxidation only in liver and kidney, but not in adrenal gland, heart or skeletal muscle. Production of 14C-labeled acid-soluble products from 1-14C-labeled fatty acids in the presence of antimycin-rotenone appears to be a more accurate and sensitive estimate of peroxisomal beta-oxidation than the acyl-CoA oxidase activity on base of H2O2 production. Chain-length specificity of acyl-CoA oxidase changed with the acyl-CoA concentrations used. Below 80 microM, palmitoyl-CoA showed the highest activity of the measured substrates in rat liver extract. No indications were obtained for the presence in rat liver of more forms of acyl-CoA oxidase with different chain-length specificity. PMID- 3342252 TI - Molecular species of mitochondrial phosphatidylcholine in rat liver and lung. AB - The acyl species of mitochondrial phosphatidylcholine from rat liver and lung were analysed by HPLC separation of the 1,2-diacyl-3-naphthylurethane derivatives. Comparison of phosphatidylcholine species patterns in microsomal, mitochondrial and submitochondrial fractions revealed only minor differences, whereas mitochondria from liver and lung differed markedly in the molecular composition of their respective phosphatidylcholine species. PMID- 3342253 TI - Selective modulation of nucleotide levels in rat liver and hepatomas by high orotate or arginine-deficient diets and by carbamoylating agents. AB - Transplanted Morris hepatomas in Buffalo-strain rats were found to be resistant to the changes in ribonucleotide levels in rat liver caused by a high-orotate diet or an arginine-deficient diet. The increase in UTP levels and decrease in ATP levels seen in the livers of rats on a 1%-orotate diet were less marked in the livers of BUB- and DBA-strain mice on this diet. Although the changes were less than in rat liver, there was a 2-3-fold increase in UTP concentration in the livers of mice on the high-orotate diet. However, there was a similar response in nucleotide levels in the two species when the animals were maintained on an arginine-deficient diet, and there was a greater than 10-fold increase in the UTP level in the livers of both rats and mice. These diets had much less effect on the levels of deoxyribonucleotides than of ribonucleotides. In contrast to the insensitivity of hepatomas to dietary modulation of nucleotide levels, treatment of hepatoma-bearing rats with carbamoylating agents (sodium cyanate and 2 chloroethyl isocyanate) caused decreases in the levels of nucleotides in the tumors which were generally greater than in host livers. For example, 2 chloroethyl isocyanate depressed ATP levels in the Morris hepatomas 5123C and 20 under conditions in which there was no significant effect on host liver ATP. The data revealed selective modulation of nucleotide levels in normal and neoplastic liver which may be achieved by either dietary modification or drug treatment. PMID- 3342254 TI - Inhibition of bone resorption in vitro by serine-esterase inhibitors. AB - The effect of two synthetic serine esterase inhibitors, N-alpha-dansyl(p guanidino)phenylalaninepiperidine hydrochloride (I 2581) and D-phenylalanyl-L prolyl-L-arginine chloromethyl ketone (D-Phe-Pro-Arg-CH2Cl), on bone resorption in organ cultured mouse calvaria from neonatal mice has been examined. Mineral mobilization was assessed by analyzing the release of 45Ca, stable calcium (Ca2+) and inorganic phosphate (Pi). Organic matrix degradation was studied by analyzing the release of 3H from [3H]proline-labelled bones, and by quantifying the amounts of hydroxyproline in bone after culture. It was found that I 2581, at and above 30 mumol/l, dose-dependently inhibited 45Ca release induced by thrombin, parathyroid hormone (PTH), prostaglandin E2 and 1-alpha-hydroxyvitamin D-3. I 2581 (50 mumol/l) inhibited PTH-stimulated release of 3H from [3H]proline labelled bones, and this effect was reversible after withdrawal of I 2581. I 2581 (50 mumol/l) inhibited the release of Ca2+, Pi, beta-glucuronidase and beta-N acetylglucosaminidase in bones stimulated by PTH and 1-alpha-hydroxyvitamin D-3, without affecting the release of lactate dehydrogenase. In parallel, I 2581 decreased PTH and 1-alpha-hydroxyvitamin D-3 induced reduction of hydroxyproline levels in bones after culture. I 2581 (50 mumol/l) did not affect the basal release of 45Ca, Ca2+, beta-glucuronidase and beta-N-acetylglucosaminidase, nor the basal amounts of hydroxyproline in bones after culture. D-Phe-Pro-Arg-CH2Cl (100 mumol/l) significantly inhibited PTH- and PGE2-induced release of 45Ca without affecting basal release of radioactive calcium. These data indicate that activation of serine proteinase(s) may be a necessary step in the mechanism of action of several stimulators of bone resorption. PMID- 3342255 TI - Distribution in cesium chloride gradients of proteoglycans of chick embryo brain and characterization of a large aggregating proteoglycan. AB - Proteoglycans were extracted from 14-day chick embryo brains, which had been labelled in vitro with [35S]sulfate or 3H-labelled amino acids. 4.0 M guanidinium chloride (containing proteinase inhibitors) extracted 94% of the 35S-labelled glycoconjugates. Following cesium chloride equilibrium centrifugation, the proteoglycans in each fraction were characterized by chromatography on Sepharose CL-2B. The most dense fraction (D1), which contained no detectable non proteoglycan proteins, contained a large, aggregating chondroitin sulfate proteoglycan in addition to small chondroitin sulfate and heparan sulfate proteoglycans. The less dense fractions (D2-D6) contained both small chondroitin sulfate and heparan sulfate proteoglycans. Removal of hyaluronate from the D1 sample by digestion with Streptomyces hyaluronidase in the presence of proteinase inhibitors showed that aggregation of the large chondroitin sulfate proteoglycan is hyaluronate-dependent. Aggregation was restored by re-addition of hyaluronate. Reduction and alkylation, which blocked aggregation of a cartilage A1 proteoglycan, did not interfere with aggregation of the large brain proteoglycan. PMID- 3342256 TI - Purification and characterization of N-acetyl-D-galactosamine-binding lectin from Falcata japonica. AB - An N-acetyl-D-galactosamine-binding lectin from Falcata japonica seeds was purified by affinity column chromatography of N-acetyl-D-galactosamine coupled to epoxy-activated Sepharose 6B. A 1000-fold purification of lectin was obtained from the crude extracts. The purified lectin agglutinated blood group A red cells, but neither blood group B nor O red cells. Polyacrylamide gel electrophoresis of the lectin showed one diffuse band. Molecular weights of 125,000 and 117,000 were estimated by gel filtration and ultracentrifugal analysis, respectively. SDS-polyacrylamide gel electrophoresis of the lectin also showed a single band which has a molecular weight of 34,000. Therefore, the lectin molecule was estimated to be a tetramer composed of four identical non covalently bound subunits. F. japonica lectin was a glycoprotein containing 5% total carbohydrate, and the amino acid composition was characterized by a high content of aspartic acid, serine and glycine, a low content of methionine and the absence of cysteine. PMID- 3342257 TI - Chemical structure of neutral sugar chains isolated from human mature milk kappa casein. AB - The carbohydrate chains linked to human kappa-casein from mature milk were released by alkaline borohydride treatment as reduced oligosaccharides. The neutral oligosaccharides of lower molecular weight were fractionated and purified by gel filtration and preparative thin layer chromatographies. Seven neutral oligosaccharides (a di- (0.5%), two tetra- (30.5%), two penta- (5.4%) and two hexasaccharide alditols (10.9%] were obtained in homogeneity, and followed by methylation analysis with gas-liquid chromatography-mass spectrometry and by anomer analysis with 13C nuclear magnetic resonance. Their chemical structures were identified to be Gal beta 1----3GalNAc-ol (I), Gal beta 1----3[Gal beta 1--- 4GlcNAc beta 1----6]GalNAc-ol (II), Gal beta 1----3[Fuc alpha 1----4GlcNAc beta 1 ---6]GalNAc-ol (III), GlcNAc beta 1----3/6Gal beta 1----3[Gal beta 1----4GlcNAc beta 1----6]GalNAc-ol (IV), GlcNAc beta 1----3/6Gal beta 1----3[Fuc alpha 1--- 4GlcNAc beta 1----6]GalNAc-ol (V), Fuc alpha 1----4GlcNAc beta 1----3/6Gal beta 1 ---3[Gal beta 1----4GlcNAc beta 1----6]GalNAc-ol (VI) and Fuc alpha 1----4GlcNAc beta 1----3/6Gal beta 1----3[Fuc alpha 1----4GlcNAc beta 1----6]GalNAc-ol (VII). Five oligosaccharide alditols (III-VII) were the novel carbohydrate chains of kappa-casein from mammalian milk. PMID- 3342258 TI - Composition of proteoglycans synthesized by rabbit aortic explants in culture and the effect of experimental atherosclerosis. AB - The synthesis of proteoglycans by aorta explants from rabbits with diet-induced atherosclerosis and controls was studied by 35S-incorporation. Proteoglycans were isolated under dissociative conditions from incubation medium and from arterial explants. Additionally, the tissue proteoglycans that were not extracted by 4 M guanidine-HCl were solubilized by digestion of the tissue by elastase in the presence of proteinase inhibitors. The residual tissue was hydrolyzed by papain and glycosaminoglycans were isolated. The atherosclerotic aorta tissue incorporated twice the amount of 35S into proteoglycans than observed for controls; in both groups about 70% of the label incorporated into the tissue was noted in the proteoglycans extracted by guanidine-HC;, while about 30% of the total 35S-labeled proteoglycans synthesized by the explants were found in the media. Atherosclerotic tissue incorporated 35S predominantly into chondroitin sulfate proteoglycans when compared to control tissue. The chondroitinase ABC digestable proteoglycans that were extracted by guanidine-HCl from atherosclerotic tissues were of larger molecular size than those from control tissue, but the core proteins from these preparations were similar. The heparan sulfate proteoglycan that was obtained by dissociative extraction from atherosclerotic tissue had greater amounts of N-acetyl and lesser amounts of N sulfate ester groups than the preparation from control tissue. Digestion of the tissue by elastase yielded heparan sulfate proteoglycan as the major constituent in both groups, although atherosclerotic tissue contained relatively small amounts of this proteoglycan. The residual tissue from both groups contained chondroitin sulfate and heparan sulfate as the major glycosaminoglycans with the latter showing a decrease with atherosclerosis. Atherosclerotic tissue secreted into the medium about two-fold more 35S-labeled proteoglycans with larger molecular size than control tissue; proteoglycans of the heparan sulfate and chondroitin sulfate types were the major constituents in the culture medium of both tissues. Thus, proteoglycans undergo both quantitative and qualitative changes in atherosclerosis, reflecting the enhanced smooth muscle cell activity. These changes are potentially important in modulating lipoprotein binding and hemostatic properties, as well as fibrillogenesis of the arterial wall. PMID- 3342259 TI - A new immunoblotting assay for thymidylate synthetase and its application to the regulation of enzyme activity in regenerating rat liver. AB - A highly sensitive and specific immunoblot assay has been developed to quantitate the content of rat liver thymidylate synthetase (EC 2.1.1.45). Applying the method, it is demonstrated that the increase of the activity of thymidylate synthetase in liver regeneration after partial hepatectomy is due to the de novo synthesis of the enzyme protein. Administration of cycloheximide, phenoxybenzamine, phorbol 12-myristate 13-acetate, nifedipine, dexamethasone or indomethacin to partially hepatectomized rats prevented the synthesis of thymidylate synthetase in regenerating liver. Thyroparathyroidectomy also inhibited the increase of the enzyme in liver regeneration. These observations are discussed in relation to the signal transduction concerning the alpha 1 receptor, which was shown to regulate liver regeneration in our previous papers. PMID- 3342260 TI - Purification and characterization of a non-kallikrein arginine esterase from dog urine. AB - A non-kallikrein arginine esterase (esterase I) has been purified from dog urine and characterized. The enzyme was purified by a three-step procedure, including ion exchange chromatography on DEAE-Sephacel, affinity chromatography on p aminobenzamidine-Sepharose, and final gel filtration on Ultrogel AcA-54. The purified preparation gave three protein bands on polyacrylamide gel electrophoresis, all of which had esterolytic activity. The enzyme has a specific activity of 601 esterase units/mg protein. It has negligible kininogenase activity. Esterase I gave two closely migrating protein bands on reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis with molecular weights of 34,000 and 33,300. Esterase I is a glycoprotein with a pH optimum of 9.5 and a pI of 4.62. The enzyme is strongly inhibited by a host of inhibitors including aprotinin, leupeptin, antipain, soybean trypsin inhibitor, lima bean trypsin inhibitor, and DPhe-Phe-Arg-chloromethyl ketone (I50 in the 10(-9)-10(-8) M range). However, p-aminobenzamidine, N alpha-p-tosyl-lysyl chloromethyl ketone and phenylmethylsulfonyl fluoride were weak inhibitors, with I50 values in the 10(-5)-10(-7) M range. The enzyme preferentially hydrolyzes Pro-Arg bonds. Among fluorogenic substrates used in this study, butyloxycarbonyl-Val-Pro-Arg methylcoumarinamide (alpha-thrombin substrate) was found to be the best, with a Km of 1.7 microM and a kcat/Km of 6.3 s.microM-1. However, esterase I does not convert fibrinogen to fibrin nor activate plasminogen to plasmin. Esterase I is immunologically distinct from dog urinary kallikrein, having no cross-reactivity with antibodies against dog kallikrein. PMID- 3342261 TI - Impairment of microsomal calcium sequestration activity upon superoxide dismutase depletion in rat liver. AB - We have studied the Ca2+-accumulation activity of microsomal vesicles isolated from the liver of rats held for from 2 to 8 weeks on a copper-deficient diet. With this treatment that deeply modifies fatty acid composition, microsomal membranes show progressively lower Ca2+ sequestration. The activity can be fully restored upon physiological copper supply to the depleted animals. The determination of kinetic parameters of microsomal Ca2+ uptake shows that copper deficiency affects mainly the apparent velocity, leaving unaffected the apparent affinity of the pump for Ca2+. Many similarities were found between this model and the Morris hepatomas with different growth rate. The data support the hypothesis that the oxidative stress imposed on the cell by the loss of superoxide dismutase can influence many cell features, with different implications in the regulation of several biological and biochemical functions. PMID- 3342262 TI - Further investigation of the use of dimethyl methylphosphonate as a 31P-NMR probe of red cell volume. AB - We have refined a method for measuring erythrocyte volume using the 31P-NMR spectrum of a probe molecule, dimethyl methylphosphonate. This compound, when added to an erythrocyte suspension, gives rise to two 31P-NMR resonances, and the frequency separation between them is linearly dependent on the intracellular haemoglobin concentration. If, for a given cell sample (under standard conditions), the separation of the two dimethyl methylphosphonate peaks has been measured and an independent estimation of the mean cell haemoglobin content and concentration has been obtained, then changes in the mean cell volume due to altered experimental conditions may be estimated from the peak separation measured under the new conditions. Although the peak separation was independent of extracellular pH, it did vary with (i) a range of extracellular suspension media, (ii) temperature, (iii) dimethyl methylphosphonate concentration, (iv) haemoglobin ligand state and (v) different blood donors. PMID- 3342263 TI - Stimulation of platelet adhesion and activation by ganglioside GD3 adsorbed to plastic. AB - Platelet interaction with gangliosides GD3, GM3, GM1, GD1a and GT1b has been investigated. These gangliosides were previously identified in the vessel wall and ganglioside GD3 was found to accumulate selectively in the intima of atherosclerotic vessels. Gangliosides were adsorbed to plastic and incubated with 51Cr-labeled platelets. The adhesion of gel-filtered platelets to ganglioside GD3 was 3-4 times higher than to other immobilized gangliosides and to albumin treated plastic. As was shown by scanning electron microscopy, GD3 stimulated intensive spreading of adherent platelets and formation of surface-bound aggregates, while only single unspread platelets were present on the surfaces coated with other gangliosides. GD3 isolated from milk and from human aorta possess the same stimulating activity. Platelet adhesion to GD3 decreased significantly in the presence of the stable prostacyclin analogue, carbacyclin. PMID- 3342264 TI - Modulation of the Ca2+-sensing function of parathyroid cells in vitro and in hyperparathyroidism. AB - When raising the extracellular Ca2+ concentration stepwise from 0.5 to 3.0 mM, bovine parathyroid cells reacted with initial transient and sustained elevations of the cytoplasmic Ca2+ concentration (Ca2+i), as well as more than 50% inhibition of parathyroid hormone (PTH) release. Human parathyroid adenoma cells and bovine cells cultured for 1 day or exposed to a low concentration of a monoclonal antiparathyroid antibody exhibited right-shifted dependencies of PTH release and Ca2+i on extracellular Ca2+ and reduced Ca2+i transients. The protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) further right shifted the dose response relationship for Ca2+ regulated Ca2+i of the adenoma cells, whereas the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2 methylpiperazine (H-7) tended to normalize it, without affecting Ca2+i of normal bovine cells. In cells from an oxyphil adenoma and a parathyroid carcinoma as well as in bovine cells cultured 4 days or exposed to a high concentration of the antiparathyroid antibody, there were no Ca2+i transients, very small increases in steady-state Ca2+i and nonsuppressible PTH release. The results suggest that reduced availability of a putative Ca2+-receptor and increased protein kinase C activity may be important factors in the decreased Ca2+ sensitivity of abnormal parathyroid cells. PMID- 3342265 TI - The effect of methylphenidate on urinary catecholamine excretion in hyperactivity: a partial replication. AB - Children with attention deficit disorder with hyperactivity were treated with methylphenidate HCl (0.74 +/- 0.2 mg/kg/day) for 2 weeks in an open trial to assess changes in the urinary excretion of catecholamines and behavior. The purpose of this study was to confirm earlier work that methylphenidate has a distinctly different effect on urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion as compared to earlier studies with dextroamphetamine. Results confirmed the earlier finding that methylphenidate does not significantly change urinary MHPG excretion. No significant relationship was found between behavioral change and any of the urinary catecholamines or metabolites measured. PMID- 3342266 TI - Serum testosterone differences between patients with schizophrenia and those with affective disorder. AB - Serum testosterone levels (ng/dl) were measured at 2-week intervals during the course of hospitalization in 35 male inpatients in the following four diagnostic groups: undifferentiated schizophrenia, paranoid schizophrenia, bipolar I disorder-manic, and major depressive disorder (endogenous type). The mean (+/- SE) testosterone levels during hospitalization were significantly higher (p less than 0.001) in the schizophrenic patients (510 +/- 38) than in the affective disorder patients (347 +/- 25). This difference persisted throughout hospitalization, being present in the first sample following admission (p less than 0.03) and the final sample before discharge (p less than 0.01). The above group differences were largely due to high testosterone levels in the paranoid schizophrenic subgroup (mean +/- SE level of 559 +/- 41). A longitudinal, as well as cross-sectional, view of the hormonal and clinical data suggests that the testosterone system is linked to both state and trait psychological factors, and this issue is discussed in the light of prior basic psychoendocrine research on this system. The potential application of these findings for new approaches to the development of biological criteria for psychiatric diagnosis is discussed. PMID- 3342267 TI - Endocrine, metabolic, and cranial computed tomographic findings in anorexia nervosa. AB - Computerized tomographic brain scans were completed in 50 inpatients with anorexia nervosa and were compared with an age- and sex-matched control group. Seventy percent of the anorectic patients displayed enlarged lateral ventricles. There was a close link between ventricular size and low weight, but not between ventricular size and duration of the eating disorder. In addition, sulcal widening was observed more frequently in patients with enlarged ventricles than in patients without these structural changes. After weight gain, a statistically significant decrease in ventricular dilatation could be observed even when mean ventricular size still far exceeded that of the control subjects. The analysis of the endocrine and metabolic parameters, known to be indicators for the process of starvation, revealed a significant inverse correlation between triiodothyronine and ventricular size. Various possible pathogenetic mechanisms for the morphological brain alterations in patients with eating disorders are discussed. PMID- 3342268 TI - Learned helplessness: an experimental model of the DST in rats. AB - Elevated ratings of anxiety and agitation in Dexamethasone Suppression Test (DST) nonsuppressors suggest a role for psychological stress in the generation of the hypothalamic-pituitary-adrenal cortical (HPAC) abnormalities characteristic of depression. We employed the learned helplessness model of depression to test the effectiveness of psychological stress in inducing a resistance of plasma corticosterone levels to dexamethasone suppression. Inescapably shocked rats exhibited corticosterone levels that were significantly more resistant to dexamethasone suppression than were the levels of rats receiving an equivalent amount of escapable shock or no shock. These results confirm the hypothesis that HPAC resistance to dexamethasone suppression is enhanced by the distress associated with the inefficacy of behavioral coping responses. The present findings represent the first analog of the DST in the learned helplessness model of depression. This DST model allows investigations into neurobiological mechanisms underlying the HPAC alterations in depression. PMID- 3342269 TI - Hydration of NaDNA by neutron quasi-elastic scattering. AB - Preliminary results of neutron quasi-elastic scattering experiments are reported for hydrated paracrystals of sodium deoxyribonucleic acid (NaDNA). The samples were investigated at two water contents: 3.5 +/- 1.0 and 9.5 +/- 1.5 mol H2O per mole nucleotide. The results of the scattering experiments were almost independent of whether the NaDNA fibers were oriented parallel or perpendicular to the momentum transfer. The data indicate that at the lower hydration the water molecules do not diffuse appreciably on the time scale of the neutron measurements (approximately 3 X 10(-10) s). At the higher hydration the water molecules diffuse isotropically in a sphere of 9 A in diameter with a diffusion coefficient of (5 +/- 2) X 10(-6) cm2 s-1. PMID- 3342270 TI - Torque and rotation rate of the bacterial flagellar motor. AB - This paper describes an analysis of microscopic models for the coupling between ion flow and rotation of bacterial flagella. In model I it is assumed that intersecting half-channels exist on the rotor and the stator and that the driving ion is constrained to move together with the intersection site. Model II is based on the assumption that ion flow drives a cycle of conformational transitions in a channel-like stator subunit that are coupled to the motion of the rotor. Analysis of both mechanisms yields closed expressions relating the torque M generated by the flagellar motor to the rotation rate v. Model I (and also, under certain assumptions, model II) accounts for the experimentally observed linear relationship between M and v. The theoretical equations lead to predictions on the relationship between rotation rate and driving force which can be tested experimentally. PMID- 3342272 TI - Biophysical Society: Program and abstracts, thirty-second annual meeting. 28 February-3 March 1988. Phoenix, Arizona. PMID- 3342271 TI - A new classification of the amino acid side chains based on doublet acceptor energy levels. AB - We describe a new classification of the amino acid side chains based on the potential energy level at which each will accept an extra (doublet) electron. The doublet acceptor energy level, and the doublet acceptor orbital were calculated using semiempirical INDO/2-UHF molecular orbital theory. The results of these calculations show that the side chains fall into four groups. We have termed these groups repulsive, insulating, semiconducting, and attractive in accordance with where each lies on the relative energy scale. We use this classification to examine the role of residues between the donor and acceptor in modulating the rate and mechanism of electron transfer in proteins. With the calculated acceptor levels, we construct a potential barrier for those residues between the donor and acceptor. It is the area beneath this barrier that determines the decay of electronic coupling between donor and acceptor, and thus the transfer rate. We have used this schematic approach to characterize the four electron transfer pathways in myoglobin recently studied by Mayo et al. (Mayo, S.L., W.R. Ellis, R.J. Crutchley, and H.B. Gray. 1986. Science [Wash. DC]. 233:948-952). PMID- 3342273 TI - Conformational unfolding in the N-terminal region of ribonuclease A detected by nonradiative energy transfer: distribution of interresidue distances in the native, denatured, and reduced-denatured states. PMID- 3342275 TI - A synthetic model of collagen: an experimental investigation of the triple-helix stability. PMID- 3342274 TI - An analysis of the 225-230-nm CD band of elapid toxins. PMID- 3342276 TI - Identification of regions of potential flexibility in protein structures: folding units and correlations with intron positions. PMID- 3342277 TI - Effect of sequence-specific interactions on the stability of helical conformations in polypeptides. PMID- 3342278 TI - Conformational studies of nucleic acids. V. Sequence specificities in the conformational energetics of oligonucleotides: the homo-tetramers. PMID- 3342279 TI - A simplified analysis of Scatchard plots for systems with two interacting binding sites. PMID- 3342280 TI - Application of the augmented theory of alpha-helix-to-random-coil transitions of two-chain, coiled coils to extant data on synthetic, tropomyosin-analog peptides. PMID- 3342281 TI - Study of the bioavailability of different formulations of 8-methoxypsoralen in the dog. AB - The absolute bioavailability of 8-methoxypsoralen in gelatin capsules and as a solution was studied in dogs. A dose of 2 mg kg-1 was given. Both for the solution and the gelatin capsules, a large variation in bioavailability was found between the different dogs. For the gelatin capsules in 1 dog out of 4 an absolute bioavailability of more than 100 per cent was found; for the solution a bioavailability of more than 100 per cent was found in all 4 dogs. Resorption was more rapid and bioavailability higher for the solution than for the gelatin capsules. Relative bioavailability of an emulsion and of a solution of 8 methoxypsoralen was studied in 2 dogs. A faster resorption and a higher bioavailability were found for the solution. PMID- 3342282 TI - Bioequivalence study of two liquid formulations of benzydamine. AB - A bioequivalence study of two liquid formulations containing benzydamine hydrochloride was carried out to evaluate the influence of a change of the excipients and the addition of a flavouring agent, ICEBERG AR 84/05/15, on the absorption of benzydamine. No statistically significant differences were observed suggesting that the two formulations are bioequivalent. PMID- 3342283 TI - Influence of food on the absorption of theophylline administered in the form of sustained release tablet and microgranules. AB - Two sustained-release formulations of theophylline, tablets (T) and microgranules (MG) forms, were administered in a randomized order to 8 healthy subjects in fasting or with a high-protein test meal (50 per cent). Blood was collected for 32h post-dose. In fasting subjects, absorption of theophylline was significantly faster for T (tmax 5 h) as compared with MG (tmax 8 h, p less than 0.05), but Cmax and AUC were comparable; intersubject variability was higher with T. Administration of a high-protein test meal with T produced a significant decrease of the zero-order absorption rate constant of theophylline (K omicron 37.8 +/- 9.1 mgh-1 after meal versus 58.8 +/- 13 mgh-1 in fasting, p = 0.01), tmax was doubled to 10 h, and Cmax increased by 25 per cent (6.33 +/- 2.16 mgl-1 versus 5.04 +/- 1.28 mgl-1, p less than 0.02); with MG, tmax were the same (8 h), Cmax were not significantly increased (4.79 +/- 0.84 mgl-1 versus 4.55 +/- 0.67 mgl 1), absorption was delayed (lag-time 1.28 +/- 0.58 h) and the absorption was slightly accelerated (K omicron 50.4 +/- 10.4 mgh-1 versus 42.3 +/- 11.9 mgh-1, NS). For each form bioavailability was not significantly modified by food. This study demonstrated that food rich in protein modifies the absorption rate of theophylline in a sustained-release tablet formulation but is without influence in a pH-independent, sustained-release microgranule formulation. PMID- 3342284 TI - Types of mean residence times. AB - Mean residence times (MRTs) have been classified into two main groups, namely system moment MRT [MRT(S,MO] and system matrix MRT [MRT(S,MA]. There are also MRTs of individual compartments [MRT(i)] such as central or plasma compartment, [MRT(P)], and tissue compartments and the MRT of an absorption site, [MRT(A)]. Much of the literature on MRTs does not clearly indicate which MRT is being discussed. MRT(S,MO) has been termed non-compartmental, but is really based on a structured model. There are really no model-independent MRTs or steady-state volumes of distribution. For the classical two-compartment open model with central compartment input, sampling and elimination MRT(S,MO) = MRT(S,MA) for a given set of microscopic rate constants. When elimination occurs from any but the central compartment then MRT(S,MO) is not equal to MRT(S,MA). For 'first-pass' drugs it is necessary to have a model where elimination occurs from a compartment different from the central and sampling compartment. Many of the methods of estimating MRTs which have been reported in the literature to date are reviewed and some generalizations are drawn. Some uses of MRTs are indicated. These uses involve both amounts of drug in the body as well as concentrations. The relationship between MRT(S,MO) and MRT(S,MA) for the Rowland two-compartment open model with peripheral compartment elimination is: MRT(S,MA)--MRT(S,MO) = 1/(k20 + k21). Thus the system matrix MRT is always larger than the system moment MRT for this linear model, which is most useful for 'first-pass' drugs. A general equation for MRT(S,MA) of all three two-compartment open models with input into either of the compartments is (lambda 1 + lambda 2 - ki0)/lambda 1 lambda 2 where i is the compartment (i = 1 or 2) into which input occurs. PMID- 3342285 TI - Dose-dependent pharmacokinetics of probenecid in the rat. AB - The basic pharmacokinetics of probenecid was studied by administration of three different i.v. bolus doses (50, 75, and 100 mg kg-1) to rats. The protein binding of probenecid in pooled rat serum was estimated by equilibrium dialysis. The unbound fraction was found to increase non-linearly with increasing total concentration, yielding a maximum free fraction of 49 per cent. The plasma concentration data obtained were described by a two-compartment model with Michaelis-Menten elimination. The maximal rate of elimination (Vm) remained unchanged between different doses irrespective of whether it was calculated in total or free concentrations (mean 187.2 +/- 8.3 (SD) microgram min-1). The Michaelis-Menten constant (Km) decreased slightly with increasing dose, while the unbound Michaelis-Menten constant (Km,u) did not change between the doses (mean 37.1 +/- 1.3 (SD) microgram ml-1). The volume of distribution of the central compartment (Vc) did not alter when the dose was increased from 50 to 100 mg kg-1 (mean 56.5 +/- 4.3 (SD) ml), but the unbound volume of distribution of the central compartment (Vc,u) decreased from 186.5 +/- 15.6 (SD) to 89.8 +/- 6.9 (SD) ml, which is in accordance with the reduction to be expected for drugs that only distribute in the extracellular fluid. PMID- 3342286 TI - Pharmacokinetics and bioavailability of etintidine in beagle dogs: effects of routes of administration, doses, dosage forms, and chronic dosing. AB - Etintidine HCl is an H2 receptor antagonist which has been under clinical trial for the treatment of duodenal ulcer diseases. Our studies are to determine the effects of routes of administration, doses, dosage forms, and chronic dosing on the bioavailability and pharmacokinetics of etintidine (E) in the beagle dog. Salient findings are: 1. Plasma levels of etintidine after i.v. administration of 200 mg of E followed a 3-exponential decay with a terminal t1/2 of 1.7h. 2. Following oral administration of 200 mg of E in capsules, tablets, or a solution dosage form to dogs, etintidine was rapidly and nearly completely absorbed with no significant first-pass elimination. 3. A proportional increase in the amount of etintidine absorbed in the dogs occurred as the administered doses increased from 30 to 180 mg kg-1 and this relationship did not change with repeated dosing. 4. Some accumulation of etintidine took place during the 52 weeks of chronic dosing. PMID- 3342287 TI - Pharmacokinetics of lidocaine and bupivacaine and stable isotope labelled analogues: a study in healthy volunteers. AB - The pharmacokinetics of lidocaine and bupivacaine and tri-deuteromethyl-labelled lidocaine and bupivacaine were investigated in healthy volunteers. The deuterium labelled and the unlabelled form of the drug to be investigated were simultaneously infused in 10 min. Plasma concentrations were determined using a combination of capillary gas chromatography and mass fragmentography. Bi exponential functions were fitted to the plasma concentration-time data. The mean distribution and elimination half-lives were 8.4 +/- 5.9 min and 96 +/- 26 min for lidocaine, 9.2 +/- 7.0 min and 98 +/- 27 min for deuterium-labelled lidocaine, 15.3 +/- 9.9 min and 111 +/- 32 min for bupivacaine, and 15.2 +/- 10.9 min and 109 +/- 31 min for deuterium-labelled bupivacaine, respectively. The mean volumes of the central compartment and mean steady state volumes of distribution were: lidocaine 37 +/- 151 and 97 +/- 201, deuterium-labelled lidocaine 39 +/- 161 and 98 +/- 181, bupivacaine 27 +/- 111 and 66 +/- 231 and deuterium-labelled bupivacaine 28 +/- 121, and 65 +/- 221, respectively. The respective mean plasma clearances were 0.88 +/- 0.181 min-1, 0.87 +/- 0.181 min-1, 0.61 +/- 0.151 min-1, and 0.62 +/- 0.171 min-1. The results of the study indicate that substitution of a deuterated methyl group does not alter the pharmacokinetics of lidocaine and bupivacaine in healthy subjects. PMID- 3342288 TI - Pharmacokinetics of 8-methoxypsoralen in the dog. AB - The pharmacokinetics of 8-MOP were studied in six dogs following intravenous administration of 2 mg kg-1. In most animals a bi-exponential decline of the plasma level profile was observed. The calculated pharmacokinetic parameters varied considerably between the different dogs. The mean half-lives of distribution and of elimination were 0.20 and 2.17 h, respectively. The average total plasma clearance was 0.51 l kg-1 h-. Following both oral and intravenous administration of doses of 1, 3, and 10 mg kg-1, non-linear kinetics were found. Non-linearity was confirmed following administration of the substance at increasing infusion rates. Finally in four dogs, extraction by the liver was calculated by measuring 8-MOP concentration in the femoral artery and in a hepatic vein after intravenous administration of 1 mg kg-1. The extraction varied from animal to animal (18 per cent to nearly 100 per cent). Administration of an additional dose of 3 mg kg-1 in two of the dogs led to a decreased extraction. PMID- 3342289 TI - Relative bioavailability of carbocysteine from three dosage forms, investigated in healthy volunteers. AB - The aim of the present study was to evaluate the bioavailability of a new tablet formulation of carbocysteine relative against two other oral carbocysteine containing dosage forms, viz. a syrup and capsules. Plasma levels and urine concentrations of carbocysteine were monitored, following oral administration of all three dosage forms to healthy human volunteers, by direct derivatization of carbocysteine using dabsylchloride and subsequent high performance liquid chromatography. There was no difference in bioavailability of carbocysteine from these dosage forms as expressed by the respective areas under the plasma concentration-time curves and total amounts of unchanged carbocysteine excreted in urine. PMID- 3342292 TI - Outcome in rheumatoid arthritis. Proceedings of a symposium. Droitwich, Worcestershire, May 8th and 9th, 1987. PMID- 3342291 TI - Red cell creatine contents in long distance runners during basal training. PMID- 3342290 TI - Interferon-alpha induction of lymphocytes containing parallel tubular structures. AB - The induction by IFN-alpha in peripheral blood lymphocytes of parallel tubular structures (PTS) and/or electron-dense granules occurring in a minority of peripheral blood lymphocytes was examined. IFN reportedly augments natural killer (NK) cell activity of large granular lymphocytes (LGL); these cells contain PTS and/or electron-dense granules. Normal peripheral blood mononuclear cells were incubated with IFN-alpha and surface antigen expression was measured by means of indirect immunofluorescence and, at the ultrastructural level, using gold labelled monoclonal antibodies. Surface antigen reactivity with the monoclonal antibodies OKT 3, 4, 8 and Anti-Leu-7 (HNK-1) showed no difference between the IFN-alpha incubation and non-IFN-alpha groups. However, electron microscope investigation revealed significant absolute increases in the percentage of OKT 8+ and Anti-Leu-7+ cells which were PTS-positive after IFN-alpha treatment compared with the control groups. The cytotoxicity assay using the K562 cell line showed enhanced lytic activity. Our results suggest that cells coexpressing the OKT 8 and Leu-7 antigens may be responsible for a minor proportion of the increase in PTS but that IFN-alpha mainly induces PTS and/or associated structures in cells which express the OKT 8+ antigen. These PTS+/OKT 8+ cells may contribute to enhanced cell cytotoxicity. PMID- 3342293 TI - Functional outcome in rheumatoid arthritis. AB - The ability to carry out daily activities depends on an individual's physical and psychological make up, and the environment and society in which he or she lives. Thus, rheumatoid arthritis produces functional impairment that is not simply related to the severity of the disease process. Two-thirds of patients are concerned more with potential loss of function than with discomfort. There is, therefore, a need to assess disability separately from inflammatory activity. The principles of disability measurement concern assessment of performance of everyday activities. Global measures or the performance of one or more specific activities can be used to assess aspects of mobility and manual dexterity. Activities can be related to social life and employment and can include assessment of psychological as well as physical disability. Many different tools are available and can be divided into: 1. Measures depending on clinical judgement. 2. Measures based on observed patient performance. 3. Measures depending on patients' opinions. In addition, a variety of health status measures have been described that include disability as one of a number of parameters aimed to assess the overall impact of the disease on the patient. Evaluation of these tools has been patchy. Full assessment using measurement theory (validity, simplicity, reliability and sensitivity) has not been undertaken for any index. However, the Health Assessment Questionnaire (HAQ) Disability Index and the Arthritis Impact Measurement Scales (AIMS) have both been tested fairly extensively in North America. The choice of a particular measurement tool depends on: 1. The context in which it will be used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342294 TI - Polyorchidism with normal spermatogenesis. PMID- 3342295 TI - Diuretic-induced urinary flow rates at varying clearances and their relevance to the performance and interpretation of diuresis renography. AB - Minute-by-minute urinary flow rates before and after the intravenous injection of 40 mg frusemide were investigated in 29 well hydrated adult patients with varying creatinine clearances. Total urinary flow rates 3 to 6 min after frusemide ranged from 1 to 42 ml/min (mean 19). At 15 to 18 min after the diuretic, flow rates ranged from 8 to 46 ml/min (mean 23). Flow rates were proportional to creatinine clearance (r = 0.73; r = 0.8) and decreased with falling clearance, although significant diuresis (4 ml/min/kidney) was achieved down to single kidney clearances of 10 ml/min. Where single kidney clearances were less than 31 ml/min, single kidney flow rates of 10 ml/min or more were not guaranteed. Below this clearance, diuresis renography remains completely reliable and unequivocal in the majority of cases. However, perfusion pressure flow studies will not necessarily be urodynamically comparable and it should not be expected that the results of the two tests will agree in individual cases of upper tract dilatation. Recommended timing for frusemide administration should be 20 min into the test, or 15 min before radiopharmaceutical injection. PMID- 3342296 TI - Acute ureteric dilatation for ureteroscopy. An experimental study. AB - The effects of three methods of acute ureteric dilatation (by graded Teflon dilators, low and high pressure balloon dilators) were evaluated radiologically, renographically and histologically in minipigs. The minipig ureter was dilated from its normal calibre of 4 F to 10 F. All three methods caused upper urinary tract dilatation and an obstructive nephropathy which had not resolved 96 h after dilatation. Histology at 24 h showed destruction of the transitional epithelium, with inflammation throughout the ureteric wall. Four weeks after dilatation the ureter was still dilated and urothelial nests were seen in the lamina propria and in the muscle coats. There was no evidence of ischaemic necrosis or ureteric stricture formation. The implications of these findings for clinical practice are discussed. PMID- 3342297 TI - The use of sacral reflex latencies in detrusor bladder neck dyssynergia. AB - Detrusor bladder neck dyssynergia (DBND) is a well recognised cause of bladder outflow obstruction, especially in the younger man. The cause is unknown, and the aim of this study was to determine if any neurological dysfunction is associated with this condition. Twenty-five males with proven DBND had sacral reflex latency studies performed. The conduction latencies indicate that the underlying cause is unrelated to any demonstrable neuropathy. Sacral reflex latencies are not helpful in the investigation of DBND. PMID- 3342298 TI - Obstructed voiding in the female. AB - Bladder outlet obstruction in women is rare. The characteristics and aetiology of the condition in 163 females are discussed and their relation to treatment evaluated. PMID- 3342299 TI - Urinary undiversion in young adults. AB - Eighteen patients who underwent urinary diversion in childhood were undiverted. There were three main groups: the neurologically intact bladder, the neuropathic bladder and the "occult" neuropathic bladder. The simplest procedure of anastomosing the proximal ureters to the distal ureters was preferred. The neuropathic group required excision of the bladder remnant and substitution with detubularised bowel. In four patients the renal function was progressively deteriorating pre-operatively and two have required transplants. Renal failure in one of these patients was accelerated by a post-operative anastomotic stenosis and infection, although his early post-operative anastomotic stenosis and infection, although his early post-operative course was uneventful. PMID- 3342300 TI - Internal iliac artery embolisation for the control of severe bladder and prostate haemorrhage. AB - Embolisation of the internal iliac artery was preformed under local anaesthesia in eight patients with severe bladder haemorrhage and in two with severe bleeding from the prostatic bed after prostatectomy. Good and effective control of the bleeding was achieved in six of the patients with bladder haemorrhage, with a partial response in the other two. Both patients with post-prostatectomy bleeding responded well to embolisation, with prompt cessation of the bleeding. This technique is recommended for the control of severe bleeding from the bladder or prostate in the seriously ill patient. PMID- 3342301 TI - Pedicled preputial patch urethroplasty. AB - Pedicled preputial patch urethroplasty has been used in 48 patients for the treatment of urethral strictures that have not responded to endoscopic surgery. The procedure is simple to perform and almost universally applicable. It avoids the problems associated with the use of scrotal skin. Its wider use is recommended. PMID- 3342303 TI - The value of testing for unmyelinated fibre, sensory neuropathy in diabetic impotence. AB - Measurement of thermal thresholds provides a means of assessing neurological deficit and in particular of recognising a neuropathic process affecting unmyelinated and small myelinated fibres of the peripheral nerve. These groups of fibres cannot be tested by nerve conduction studies but are particularly susceptible to disease in diabetes. Thresholds for thermal sensation on the sole of the foot were measured in 33 men presenting with erectile dysfunction. All 15 men with erectile dysfunction, which had been considered on clinical grounds to be neuropathic, had abnormal thermal thresholds. Diabetics with non-neuropathic erectile dysfunction had normal results. Whereas tests of unmyelinated sensory fibre function were abnormal in all those with neuropathic erectile dysfunction, electrophysiological measurement of the bulbocavernosus reflex was normal in five of nine men with diabetic neuropathic impotence. PMID- 3342302 TI - Bulbocavernosus reflex latency in the investigation of diabetic impotence. AB - Impotence in males is a well recognised complication of diabetes mellitus, commonly held to be due to an autonomic neuropathy. The aim of this study was to determine the incidence of periphero-conus neuropathy in diabetic impotence. Nineteen diabetic males seeking treatment for loss of potency had bulbocavernosus reflex latency (BCRL) and sacral reflex latencies (SRLs) performed. The conduction studies indicated that impotence in these cases was associated with peripheral neuropathy in 21% of patients and that BCRL and SRLs are sensitive and useful diagnostic tests. PMID- 3342304 TI - Neurophysiological investigation of diabetic impotence. Are sacral response studies of value? AB - The role of electrophysiologically elicited sacral responses in the detection of the neurological component of diabetic impotence has been evaluated in a detailed study using properly defined diagnostic criteria. The results prove that these tests are not reliable indicators of neuropathy and their relevance in the routine investigation of diabetic impotence is of questionable value. PMID- 3342305 TI - Abstracts of the proceedings of the Urological Society of Australasia, 40th annual scientific meeting, Rotorua, New Zealand, 1987. PMID- 3342306 TI - Methodology, results and complications in 2000 extracorporeal shock wave lithotripsy procedures. AB - Since the installation of an extracorporeal shock wave lithotriptor (ESWL) unit 12 months ago, 2000 lithotripsy procedures have been performed. Overall, 68.4% of patients were stone-free by the end of the first month. Residual lithiasis (fragments less than 0.5 cm) was seen in 19.7% of patients and significant lithiasis (fragments greater than 0.5 cm) was observed in 10.1%. Complications were obstruction, infection, headache due to the epidural anaesthesia, anuria, renal failure, perirenal haematoma and cardiac arrest. A number of patients required additional operative treatment; this was always endoscopic and no open procedures were performed. Hospitalisation averaged 1 day. PMID- 3342307 TI - Trazodone-induced priapism. PMID- 3342309 TI - Bladder calculus. A rare complication of ureteric reimplantation. PMID- 3342308 TI - Blu-tack in the bladder. PMID- 3342310 TI - Bilateral vasocutaneous urinary fistula. PMID- 3342311 TI - Giant malignant phaeochromocytoma. PMID- 3342312 TI - Papillary endometrioid carcinoma of the prostate. PMID- 3342313 TI - Primary malignant lymphoma of the testis: diagnosis and management. PMID- 3342314 TI - Sensitivity to inflectional morphology in agrammatism: investigation of a highly inflected language. AB - We present the results of a study with six Serbo-Croatian-speaking agrammatic patients on a test of inflectional morphology in which subjects judged whether spoken sentences were grammatical or ungrammatical. Sensitivity to two kinds of syntactic features was investigated in these aphasic patients: (1) subcategorization rules for transitive verbs (which must be followed by a noun in the accusative case; intransitive verbs can be followed by nouns in other noun cases); (2) sensitivity to the inflectional morphology marking noun case. The test items consisted of three-word sentences (noun-verb-noun) in which verb transitivity and appropriateness of the case inflection of the following noun were manipulated. Results of the grammaticality judgment task show that both syntactic properties are preserved in these patients. PMID- 3342315 TI - The role of the right hemisphere in the production of linguistic stress. AB - Recent research has proposed a general prosodic disturbance associated with right hemisphere damage (RHD), one encompassing both affective and linguistic functions. The present study attempted to explore whether the ability to produce linguistic prosody was impaired in this patient population. Productions of phonemic stress tokens (e.g., Re'dcoat vs. red coa't) as well as examples of contrastive stress, or sentential emphasis (e.g., Sam hated the movie), were elicited from eight male speakers with unilateral right hemisphere CVAs and seven male control subjects. Two types of analyses were conducted on these utterances. Acoustic analysis focused on the correlates associated with word stress, namely changes in amplitude, duration, and fundamental frequency. The perceptual saliency of emerging cues to stress was also examined by presentation of test tokens to phonetically trained listeners for identification of stress placement. The patients as a group produced fewer acoustic cues to stress compared to the normal subjects, but no statistical differences were found between groups for either stress at the phrase level or at the sentence level. In the perceptual analysis, stress produced by the patient group was judged to be less salient than that for the normal group, although a high degree of variability was evident in both populations. The data suggest a spared processing mechanism for linguistic prosody in RHD speakers, thus mitigating against the view of a general dysprosody tied to RHD. PMID- 3342316 TI - Language production in Parkinson's disease: acoustic and linguistic considerations. AB - The hypokinetic dysarthria of Parkinson's disease (PD) has been described extensively. In contrast, patterns of hesitation and the language structure in spontaneous speech of the PD patient have not been investigated, although several studies have shown language-related abnormalities in word naming, word generation, and verbal recall. In the present study, 10 male Parkinson's patients and 10 normal male speakers were compared in a reading and spontaneous speaking paradigm for acoustic and linguistic features. Among acoustic measures, fundamental frequency and relative intensity differentiated PD from control subjects, consistent with reported features of hypokinetic dysarthria. The striking observations among linguistic measures differentiating PD from control subjects were an increase in the number of (a) silent hesitations per minute, (b) abnormally long silent hesitations, (c) words per silent hesitation, (d) open class phrases, and (e) optional open phrases per speech sample, and a decrease in the number of modalizations and interjections. An increase in the number of filled hesitations occurring per minute, as well as a decrease in syntactic complexity separated moderate from mild Parkinson's patients. Our interpretation of the data favors the hypothesis that changes in the structure of spontaneous language production with increasing severity of dysarthria reflect PD patients' adaptation to their disease. PMID- 3342317 TI - Hemispheric processing of affective and linguistic intonation contours in normal subjects. AB - In a previous study of the comprehension of linguistic prosody in brain-damaged subjects, S. R. Grant and W. O. Dingwall (1984. The role of the right hemisphere in processing linguistic prosody, presentation at the Academy of Aphasia, 1984) demonstrated that the right hemisphere (RH) of nonaphasic patients plays a prominent role in the processing of stress and intonation. The present study examines laterality for affective and linguistic prosody using the dichotic listening paradigm. Both types of prosody elicited a significant left ear advantage. This advantage was more pronounced for affective than for linguistic prosody. These findings strongly support previously documented evidence of RH involvement in the processing of affective prosody (R. G. Ley & M. P. Bryden, 1982. A dissociation of right and left hemispheric effects for recognizing emotional tone and verbal content, Brain and Cognition, 1, 3-9). They also provide support for the previously mentioned demonstration of RH involvement in the processing of linguistic intonation (S. Blumstein & W. E. Cooper, 1974. Hemispheric processing of intonation contours, Cortex, 10, 146-158; Grant & Dingwall, 1984). PMID- 3342318 TI - Different modes of word recognition in the left and right visual fields. AB - We confirm previous evidence indicating that word length has a substantial effect on word recognition in the LVF but a much weaker effect in both the RVF and fovea. The nature of encoding in the LVF is not altered when the words are vertically displayed (Experiment 2), and the effect cannot therefore be entirely due to scanning artefact or acuity gradients in peripheral vision. We provide evidence that links the asymmetrical influence of word length directly to hemispheric specialization: left-handers, who as a group are much less consistently lateralized than right-handers are also less affected by word length in the LVF on the average (Experiment 3). This occurs because the asymmetry for certain left-handers is either very weak or, in some cases, is the complete reverse of the asymmetry observed in right-handers. Finally, we demonstrate that the length x field interaction is observed in lexical decisions (Experiment 4) which do not entail pronunciation of written words. There is some indication that concrete, high-imageable words produce a smaller effect of length in the LVF than abstract, low-imageable words, and we discuss this outcome in relation to the proposal that the right hemisphere can sometimes extract a lexical code from letter information. The concept of distinct modes of word recognition in the LVF and RVF clarifies a number of issues in laterality research, and suggests a new approach to evaluating group differences in half-field performance. PMID- 3342319 TI - Reading mirror-reversed text: sinistrals really are inferior. AB - R. Tankle and K. M. Heilman (1982, Brain and Language, 17, 124-132) reported a sinistral superiority in obligatory reading of left-right mirror-reversed material. Their subjects included weak left- and right-handers. J. L. Bradshaw, N. C. Nettleton, L. Wilson, and V. Burden (1985, Brain and Language, 26, 322-331) employed a variety of geometrically transformed text, including mirror-reversed, and found that strong familial sinistrals were either not different from or were even slightly inferior to dextrals in reading most transformations, including left-right mirror reversals. We now report a study using subjects selected according to criteria similar to those of Tankle and Heilman, and find under these conditions that sinistrals are indeed significantly inferior to dextrals. PMID- 3342320 TI - Nonverbal communication as a compensative strategy for severely nonfluent aphasics? A quantitative approach. AB - Seven severely nonfluent aphasics and one relative or close friend were investigated in an interview situation. The conversation was videotaped and analyzed for the use of nonverbal communication between aphasic and partner. The results indicate that the group of aphasics used significantly more frequently and for a significantly longer period of time nonverbal channels of communication than their healthy partners. The aphasic patients also used significantly fewer speech-focused movements and significantly more codified gestures. Nonverbal elements were more frequently used as speech substitutes by the group of aphasics. PMID- 3342321 TI - Cerebral hemispheric mechanisms in the retrieval of ambiguous word meanings. AB - Targets related to ambiguous primes were projected to the left and right visual fields in a lexical priming experiment with stimulus onset asynchronies (SOA) of 35 and 750 msec. Right visual field results were similar to our earlier results with central projection (G. B. Simpson & C. Burgess, 1985, Journal of Experimental Psychology: Human Perception and Performance, 11, 28-39). Facilitation was found for the more frequent meaning at both SOAs and a decrease in facilitation for the less frequent meaning at the longer SOA. In contrast, left visual field results indicated a decay of facilitation for the more frequent meaning at the longer SOA, while activation for the subordinate meaning increased. Results suggest that, while automatic processing occurs in both hemispheres, only the left hemisphere engages in controlled processing of ambiguous word meanings. In addition, the present results support the idea that the right hemisphere has a special role in ambiguity resolution and that the right hemisphere lexicon possesses a richer endowment than earlier thought. PMID- 3342322 TI - Proliferation of Schwann cells in a developing feline lumbar ventral spinal root. AB - Schwann cell proliferation in the L6 ventral spinal root of cat fetuses and young kittens was studied by light microscopical autoradiography and electron microscopy. The proliferative activity reached a maximum 35 days after mating. This is about one week before the immature alpha-axons begin to myelinate and about one month before birth (63 days after mating) when the myelination of the immature gamma-axons starts. The proliferative activity was already quite low 45 days after mating and ceased completely after birth. Calculations based on the observed number of Schwann cell nuclei per 100 axons showed that the number of Schwann cells already present 45 days after mating was equal to or even a little higher than the observed adult number. Necrotic nucleated Schwann or endoneurial cells were not observed. I conclude that Schwann cell proliferation in the L6 ventral spinal root is already nearly finished when the first immature alpha axons begin their myelination and that myelination of the immature gamma-axons begins without a preceding increase in Schwann cell proliferative activity. PMID- 3342323 TI - Axon elimination in the developing corticospinal tract of the rat. AB - Quantitative ultrastructural analysis of the corticospinal tract (CST) at the mid thoracic spinal level in a series of early postnatal and young adult rats reveals that the tract is initially composed primarily of morphologically immature axon shafts, growth cones, and pale neuroglial processes. The total number of axons in the tract rises quickly to a peak level up to 90% greater than that present in the adult tract; it then declines, contemporaneously with the restriction of the areal extent of the set of spinally projecting cells in the cerebral cortex. During the time of axon elimination, axons remain small and morphologically immature, and small numbers of growth cones persist. Glial cells take on more mature forms within the tract several days before axon outgrowth ceases and myelination begins at the end of the second postnatal week. The fully mature CST retains a large complement of small, unmyelinated axons. PMID- 3342324 TI - Cholecalcin (28-kDa CaBP) in the rat cochlea. Development in normal and hypothyroid animals. An immunocytochemical study. AB - The distribution of cholecalcin (28-kDa calcium-binding protein) in the cochlea of developing rats was followed by immunocytochemistry. In normal animals, the protein first appeared in utero in the cells of Kolliker's organ, a structure involved in the secretion of the tectorial membrane. The inner hair cells, followed by the outer hair cells, then became immunoreactive from the base of the cochlea to the apex. Their cuticular plate, the anchoring structure for stereocilia, was particularly labeled. The cells of Kolliker's organ lost their immunoreactivity after the first postnatal week, the time when they lose their secretory activity. During the same period, when the tunnel of Corti and the space of Nuel open, labeling appeared in the supporting cells. The neurons of the spiral ganglion were stained from the second postnatal week and the fibers of the cochlear nerve after the end of the first month. No difference was induced by thyroid deficiency until the second postnatal week. Thereafter, Kolliker's organ did not transform and its cholecalcin immunoreactivity persisted, together with the secretory activity. As a result, the tectorial membrane was greatly distorted and the mechanical properties of the organ of Corti were dramatically impaired. The supporting cells were labeled although the tunnel of Corti and the space of Nuel did not open. Staining of the spiral ganglion neurons was delayed. All the nervous structures of the cochlea were, however, stained at the end of the first postnatal month, as in normal animals, despite the irreversible complete deafness. Cholecalcin is thus present during development of the cochlea in both non-neuronal and neuronal structures, and is probably involved in very different processes in various types of cells. PMID- 3342325 TI - Triiodothyronine (T3) induces neurite formation and increases synthesis of a protein related to MAP 1B in cultured cells of neuronal origin. AB - Neuroblastoma (N2A) cells were found to develop axon-like neurite extensions when grown in the presence of triiodothyronine (T3), while C6 cells (of glial origin) did not. Analysis of radiolabelled protein synthesis showed that, in N2A only, T3 increased the synthesis of a polypeptide corresponding in electrophoretic mobility to the microtubule-associated protein MAP 1B. Immunoblotting of total cell proteins with a monoclonal antibody confirmed that this polypeptide was immunologically related to MAP 1B. Further studies using indirect immunofluorescence with monoclonal antibodies against both tubulin and MAP 1B showed that both antigens were present in neurites. Taken together, these results suggest that T3 may control maturation of neural tissue via effects on the microtubule-associated proteins in cells of neuronal origin. PMID- 3342326 TI - Failure of kindling to alter susceptibility to kainic acid. AB - In this study, the interaction between electrical kindling and kainic acid seizures was investigated. Prepubescent male rats were kindled using hourly, suprathreshold stimulations. Two days later the kindled rats and their non kindled controls received systemic injections of either 6, 10, or 17 mg/kg of kainic acid. No differences in response to kainic acid were seen between the two groups. These data demonstrate that the kindled brain does not uniformly exhibit a lower seizure threshold to all convulsants, but is dependent on the agents subsequently used to induce the seizures. PMID- 3342327 TI - Species specificity in the responsiveness of chick embryo neural tube explants to target-conditioned medium. AB - Explants from the metencephalic region of 40-h chick embryo neural tubes containing the trigeminal (V) motor nucleus were cultured in appropriate target muscle-conditioned media (MCM) derived from chick, quail and rat embryos. Enhanced neuritic outgrowth was found only in the presence of chick MCM, indicating that this early, initial responsiveness to target-released materials within this system is species-specific. PMID- 3342328 TI - Production in vitro by spinal cord of growth factor(s) acting on newt limb regeneration: influence of regeneration of the nerve fibers. AB - In order to approach the problem of regulation of growth factor(s) production during limb regeneration in newt, we co-cultivated spinal cord segments and blastemas. First we showed that, like the sensory supply, the spinal cord possesses size-dependent mitogenic capacities for limb blastemas. A 5-mm long spinal segment enhances radiolabelled thymidine incorporation to the same extent as spinal ganglia (1.6-fold). Second, we co-cultivated blastemas with spinal segments, the nerve fibers of which were previously stimulated to regenerate (= stimulated spinal segment) or not (= non-stimulated spinal segment). Only after a 24-h coculture, do stimulated spinal segments enhance thymidine incorporation in blastemas 2-fold more than non-stimulated spinal segments. Our results suggest that during limb regeneration brachial nerves produce more growth factor(s) when regrowing, inducing the proliferation of blastema cells which in return deliver a neuronotrophic factor acting on these nerves. PMID- 3342329 TI - The effects of ablation of visual cortex in neonatal rabbits on the organization of retinothalamic and retinopretectal projections. AB - Primary visual cortex was ablated unilaterally in neonatal rabbits. Following a survival of 2-4 months, retrograde degeneration of the dorsal lateral geniculate nucleus (LGd) was assessed, and reorganization of retinofugal pathways was studied using methods of anretrograde transport of [3H]proline or of horseradish peroxidase. A complete lesion of primary visual cortex resulted in complete retrograde degeneration of the LGd with no sparing of any class of neurons. The terminations of retinofugal axons in the pretectum and thalamus were compared with those observed in normal animals. No major reorganization of ipsilateral retinofugal projections was observed in either the thalamus and pretectum ipsilateral to the ablated cortex, or in the thalamus and pretectum contralateral to the ablated cortex. However, contralateral retinofugal projections to the thalamus and to the pretectum ipsilateral to the ablated cortex were significantly different from normal. In the thalamus, the projections to the lateral posterior nucleus were expanded in area and increased in density. In the pretectum, the projections to the rostral pretectal areas were greatly increased in area, especially in the region of the olivary pretectal nucleus and posterior pretectal nucleus. However, the density of these projections was not increased relative to normal. Consideration of these results in relation to other published data on the anatomical consequences of neonatal visual cortex lesions, both in mammals which show behavioral sparing following neonatal visual cortex lesions and in mammals which, like the rabbit, show no behavioral sparing, suggests that: (1) behavioral sparing may correlate with patterns of survival or death of neurons in the thalamus and retina; and (2) reorganization of retinofugal pathways is not necessarily associated with behavioral sparing. PMID- 3342330 TI - Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. I. Stepping in normal kittens. AB - Neuromuscular patterns associated with the development of hindlimb stepping behaviors were studied from birth to postnatal day 60 in normal kittens. Hindlimb muscles were chronically implanted with EMG electrodes at birth to characterize interlimb coordination and intralimb synergies during development of overground and treadmill stepping. Airstepping was also examined but seldom occurred after the second postnatal week. All kittens performed stepping under each condition, including weight-supported stepping, by postnatal day 3. The number of sequential steps on the treadmill and overground increased with age and cycle periods decreased. At onset, stepping behaviors were characterized by adult-like EMG patterns. Interlimb coordination was typified by alternating extensor bursts of similar duration. Extensors at the knee and ankle were coactive during the stance phase, and extensor burst durations were strongly correlated with the cycle periods over a wide range of stepping frequency. Ankle flexor and extensor muscles were reciprocally active during postural tremor, bouts of airstepping, and weight-supported steps on the treadmill and overground. The duration of the reciprocal flexor bust did not vary with cycle period or age. Observations of stepping behaviors and adult-like EMG patterns during initial postnatal development were contingent on optimal testing conditions. Taken together, the data suggest that pattern-generating circuits for regulating interlimb coordination and intralimb muscle synergies are potentially functional prior to the normal ontogenetic onset of locomotion. Perhaps the prolonged postnatal development of locomotion reflects the time required to establish adaptive mechanisms, such as postural control and agility, rather than spinal pattern generating circuits for locomotion. PMID- 3342332 TI - Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. III. Scratching and the paw-shake response in kittens. AB - Neuromuscular patterns of scratching and the paw-shake response were studied in normal kittens from birth to postnatal day 60. Onset of both behaviors coincided with the development of secure weight-bearing posture and occurred on postnatal day 21 for scratching and postnatal day 26 for paw shaking. At onset, cycle periods for scratching (5-6 Hz) and paw shaking (8-10 Hz) were similar to that for adult cats, and EMG patterns were adult-like. The scratch cycle consisted of reciprocal flexor and extensor bursts of equal duration, while the shake cycle consisted of coactive knee extensor and ankle flexor bursts alternately active with ankle extensor bursts. The lack of scratching and paw shaking during the first 3 postnatal weeks and the adult-like EMG patterns at onset are consistent with the hypothesis that pattern-generating circuits within lumbosacral segments are available early in development but inhibited by the rostral neuraxis until postural control is sufficient to accommodate the response. To eliminate rostral inputs, including descending input critical for postural control, kittens were spinalized at the T12 level, and onset of paw shaking was accelerated. In kittens spinalized at birth, paw-shake onset occurred on postnatal day 14, while in kittens spinalized on postnatal day 14, onset occurred 48 h after spinalization. In all spinal kittens, however, knee extensor activity was disrupted and not normal by postnatal day 60. Mature neuromuscular patterns for scratching and paw shaking are available at onset of the behavior during normal development. Spinalization hastens the onset of paw shaking but the normal neuromuscular synergy is disrupted as well as the temporal structure of the multi-cycle response. Disruptions following spinalization may be due to altered development of spinal pattern generators or aberrant feedback from atypical hindlimb motions due to a retardation of hindlimb growth and an alteration of muscle contractile properties in spinal kittens. PMID- 3342331 TI - Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. II. Stepping in spinal kittens. AB - From birth to postnatal day 60, neuromuscular patterns for airstepping and treadmill stepping were assessed in kittens spinalized (T12) at birth (Day-1) or at the end of the second postnatal week (Day-14). Within 72 h after spinalization, all kittens displayed stepping motions, but exteroceptive facilitation (e.g. tail pinch) was required to initiate and sustain both behaviors. In Day-14 spinal kittens, the hindlimbs spontaneously and alternately airstepped, but in Day-1 spinal kittens exteroceptive stimulation was usually necessary to evoke airstepping, and the hindlimbs stepped synchronously. Kittens in both groups developed atypical neuromuscular patterns; flexor bursts were nearly twice as long in duration as extensor bursts. Development of bipedal treadmill stepping was similar for Day-1 and Day-14 spinal kittens, but differed from that for normal kittens. Tested at the same belt speeds, stepping was more easily elicited in spinal kittens, bouts of repetitive stepping were longer, and cycle periods were shorter than in normal kittens until postnatal week 6. Spinal kittens, however, seldom exhibited adequate weight support during hindlimbs stepping, and the neuromuscular patterns associated with bipedal stepping were atypical. For spinal kittens, the relationship between the extensor burst duration and the cycle period was reduced substantially, and flexor activity was initiated earlier in the step cycle and was longer in duration than that for normal kittens. These atypical intralimb synergies may have been the consequence of altered lumbosacral circuits produced by the spinal transection. It is also possible that these spinal circuits, lacking rostral input, were particularly susceptible to abnormal motion-dependent feedback resulting from reduced hindlimb weight support. PMID- 3342333 TI - Topographical distribution in the adult rat brain of neurotrophic activities directed to central nervous system targets. AB - Cortex, hippocampus, septum and striatum of day 18 rat embryos were grafted to several brain regions of young adult rats which had been lesioned in the chosen area 4 days earlier. Thirty days after transplantation, the grafts were fixed and morphometrically analysed under light microscope. The volumes, neuronal densities and total number of neurons of the transplants were compared. Each graft survived best when transplanted to its original region. Good survival was also achieved by heterotopic grafts between regions that are anatomically related. Striatal grafts showed reasonable survival only when transplanted to their original site. In a second series of experiences, the neurons from the same embryonic brain regions were cultured in a defined medium, to which was added tissue extracts from the lesioned regions of the adult brain. The neuronal survival was estimated. The in vitro results are closely related to those obtained in vivo. This experimental evidence agrees with the theory of the existence of a retrograde transport of NGF from the hippocampus to the septum, sustaining the survival of the latter. On the other hand, our results demonstrate the existence of other unidentified neurotrophic factors in the central nervous system which differ from one region to another. PMID- 3342334 TI - Spatial organization of the peripheral input to area 1 cell columns. I. The detection of 'segregates'. AB - Extracellular single neuron recording methods are used to study the RFs of neurons comprising area 1 cell columns in unanesthetized Macaca fascicularis monkeys. The RF data obtained in approximately radial microelectrode penetrations demonstrate that the RFs of neurons located within the same area 1 cell columns can differ strikingly, and that it is common for neighboring neurons to possess RFs differing greatly in size or configuration. However, the RF variations detected within a typical area 1 cell mini-column (single cell radial column) appear to be substantially less than the variations observed for nearby neurons lying in different minicolumns. The RF data obtained from arrays of penetrations suggest that the skin representation in the forelimb region of area 1 is organized in a discontinuous, step-like fashion: as a mosaic of discrete 600 micron wide radial cell columns--segregates. Although the RFs of neurons of a segregate can vary substantially in size and configuration, they all share in common a single small area on the skin. The boundaries of a segregate can be mapped precisely because, unlike the situation for neurons located within the same segregate, some of the neurons located on opposite sides of a segregate boundary (belonging to different segregates) have non-overlapping RFs. Furthermore, it appears that within any given segregate there is no systematic shift in RF location as the electrode advances through a sequence of minicolumns. Systematic RF shifts occurred only when the electrode traversed the boundary between neighboring segregates. PMID- 3342335 TI - Spatial organization of the peripheral input to area 1 cell columns. II. The forelimb representation achieved by a mosaic of segregates. AB - The view (advanced in the previous paper) that the topographic organization in the forelimb region of area 1 of Macaca fascicularis monkeys should be regarded as a mosaic of discrete units--segregates--is evaluated. It is found that in all cortical layers the RFs sampled within a single segregate possess a wide variety of sizes and configurations, and occupy a wide variety of positions on the skin relative to the segregate RF center (the latter is a small skin area common to RFs of all neurons in the segregate). This within-segregate RF variability is structured so that the position of RFs of neurons sampled from different sectors of a segregate exhibits little, if any, systematic shift. The skin area that provides sensory input to any given area 1 segregate (estimated by the aggregate of the RFs sampled from that segregate) is extensive. This 'segregate RF', however, is not homogenous: i.e. central regions of the segregate RF are included in the RFs of a higher fraction of the neurons in the segregate than are peripheral regions. Segregate RFs appear particularly extensive when their size is compared with a relatively small shift in skin position that takes place when one shifts from one segregate to the next. Consequently, the skin areas that provide the sensory inputs to neighboring segregates overlap to a very large degree; and even fairly remote segregates in area 1 can receive a substantial common input. The arrangement of segregate RFs in area 1 is, in general, somatotopic. Nevertheless, the local relationships that are obtained among different segregates can deviate significantly from a strictly somatotopic pattern. The area 1 topographic organization detected in this study appears to differ substantially from that described by other investigators. A more detailed analysis suggests that most of the major differences between this and the previous descriptions of area 1 organization may largely be attributable to the different experimental conditions employed, and that the results of this study and those described by workers using different mapping methods are, in fact, generally compatible. Finally, it is suggested that the mosaic pattern of the topographic organization detected in area 1 may reflect the bundled nature of its afferent input. PMID- 3342336 TI - Comparison of ongoing compound field potentials in the brains of invertebrates and vertebrates. AB - (1) Ongoing compound field potential fluctuations of higher brain centers (the micro-EEG of some authors) are considered as a biological phenomenon, a sign of the activity in the organized assemblage of cells. Such activity has been compared in several taxa with quite different brain structure to look for possible evolution in the form of the field potentials and for possible explanations of differences and similarities. (2) Recordings were made with semimicroelectrodes in the neuropile of the cerebral ganglion of the mollusc, Aplysia, with comparative observations on Helix, and the arthropods Limulus, Melanoplus, and Cambarus, and in or on the cerebral cortex and optic tectum of rays, cats and rabbits, with comparative observations on sharks, bony fish, turtles and geckos in unstimulated resting or generalized arousal states. Manipulations of state did not alter the main findings. (3) Power spectra in the cerebral ganglia of various higher invertebrates are similar; activity is fast and spikey (with the exception of Octopus). Integrated energy above 50 Hz exceeds that from 2-50 Hz and falls slowly with frequency; in Aplysia the power spectrum falls less than 10 dB between 10 and 300 Hz. In vertebrates from fish to mammals activity is similar in being mainly slow (less than 40 Hz); it commonly falls greater than 20 dB between 10 and 50 Hz. (4) Amplitude is low in invertebrates and lower vertebrates. RMS voltage in Aplysia (3-300 Hz, reference electrode remote) is typically less than 10 microV; in the ray optic tectum less than 25 microV (2-50 Hz); in the dorsal cortex of the gecko less than 30 microV, in the cat cortex greater than 85 microV. In the vertebrates amplitude does not change greatly with small shifts in electrode position, as it does in invertebrates. (5) Coherence decline with distance, measured tangentially at different electrode separations in the millimeter range, is used as an estimator of synchrony. Averaged coherence between loci 1 mm apart is negligible in Aplysia in any band from 3 to 100 Hz; in the ray tectum it is low, 0.25-0.5 between 3 and 16 Hz. In the turtle dorsal pallium it is higher, at 2 mm, 0.6-0.75 in this band. In the rabbit cortex coherence is even higher, typically greater than 0.7 at 1 mm, and greater than 0.3 at 4 mm in this band. (6) Band-pass filtered electrograms, ca. one octave wide, in all species show constant waxing and waning in each band; amplitude is not maintained even for a second. (ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3342337 TI - Peptide radioimmunoassays: a BASIC program for data reduction. AB - A BASIC computer program is listed and described which may be used for calculating large amounts of data generated by radioimmunoassays. The user is given the opportunity to construct standard curves and to calculate mass quantities from raw counts or to incorporate previously determined protein values with mass quantities for final data expression. Calculated data may be viewed onscreen or obtained as printed copy. PMID- 3342338 TI - Cardiovascular effects of microinjection of adenosine into the nucleus tractus solitarius. AB - Rats were anesthetized with urethane and limited occipital craniotomy was conducted to expose the caudal medulla in the region of the obex. Microinjections of adenosine were made into the nucleus tractus solitarius and heart rate and blood pressure responses recorded. Adenosine produced dose-related decreases in blood pressure and heart rate. The data indicate that adenosine may play a neuromodulatory role in central cardiovascular control areas. PMID- 3342340 TI - Isolation of glycosaminoglycans from basement membranes of brain microvessels. AB - Although the core protein of a heparan sulfate proteoglycan has been detected in brain microvessel basement membranes by immunoperoxidase staining, cytochemical evidence of a glycosaminoglycan component, in the form of discrete staining with ruthenium red, is not found. To resolve this discrepancy, we examined the glycosaminoglycan content of this basement membrane directly. Microvessels were isolated from pig cerebral cortex, and basement membranes freed from cellular elements. Following digestion with papain and Pronase, the glycosaminoglycans were precipitated with cetyl pyridinium chloride and ethanol. The resulting extract contained uronic acid, and after electrophoresis on Super Sepraphore revealed 2 bands: One co-migrated with heparan sulfate standard, the other with chondroitin sulfate A and C. The first was completely eliminated by nitrous acid and heparitinase, but not by hyaluronidase or chondroitinase ABC and was therefore confirmed as heparan sulfate; the other band was eliminated by chondroitinase ABC but not by the other three treatments. The findings suggest that basement membrane of brain microvessels, like other vascular basement membranes, contains heparan sulfate and chondroitin sulfate A and/or C. The failure of staining with ruthenium red is probably a result of unique structural features of this basement membrane, rather than an absence of glycosaminoglycan. PMID- 3342339 TI - A microcomputer-based sleep system: data acquisition and system calibration programs. AB - A data acquisition program is described for the Apple II series of microcomputers that allows for continuous, direct monitoring of electrographic elements from cortical, hippocampal and muscle leads from rats. The program detects cortical delta waves and sigma activity, hippocampal theta activity and electromyographic activity. The detected elements are counted and stored in memory at 15 second intervals (bins). Every three hours, the data are transferred to disks for permanent storage and off-line analysis. PMID- 3342342 TI - Cocaine produces fine structural nuclear alterations in cultured neuroglioblastoma cells. AB - NG 108-15 neuroglioblastoma cells were grown in culture medium containing either 10(-3), 10(-6) or 10(-9) M cocaine for 1-3 days. Some cultures were assessed for viability while others were processed for electron microscopy. Following 1-3 days of cocaine, no cytoplasmic alterations were observed compared to control; however, numerous dense bodies were present in some cells cultured with the highest doses. After 2 days of treatment with 10(-3) and 10(-6) M cocaine, nuclear invaginations were found filled with vesicles, and the nuclear membrane surrounding the vesicles was disrupted. Following 3 days of treatment with 10(-3) and 10(-6) M cocaine, patches of vesicles and tubules were also seen in the nucleus, but without surrounding membranes. The vesicles ranged in size from 0.05 to 0.8 micron. Cell counts revealed a significant slowing in the rate of cell division after two days of exposure to 10(-3) M cocaine. All concentrations of cocaine caused a significant decrease in cell viability by the third day of treatment. These results suggest that cocaine may interfere with cell replication and also may have a neurotoxic effect. PMID- 3342341 TI - Ultrastructural changes in the rat neurohypophysis following castration and testosterone replacement. AB - Ultrastructural changes in male rat neurohypophyses were studied 8 or 30 days after castration, with or without testosterone (T) replacement via capsule implants. Morphometric analyses determined the: (a) amount of neural contact at the basal lamina (BL) of the neurovascular contact zone, (b) average length of individual terminal contacts with the BL, (c) number of neurosecretory terminals per 100 micrograms of BL, and (d) mean number of enclosed axonal processes per pituicyte. Eight days after castration there was decreased neural/BL contact and increased pituicyte enclosure of neurosecretory processes, conditions associated with decreased hormone release. In contrast, T replacement resulted in increased individual nerve terminal length, a measure associated with increased hormone demand. This observation may indicate a stimulatory effect of continuous high normal circulating levels of testosterone from the capsule implants. There were no differences from control in 30-day castrate rats, but the 30-day rats with T replacement showed morphological indications of increased hormone release. These consisted of increased neural contact with the BL apparently through a significant increase in the number of neurosecretory terminals per unit length of BL. These findings support studies showing a complex feedback interaction between circulating levels of testosterone and vasopressin release. PMID- 3342343 TI - Labyrinthine projection to the hypoglossal nucleus. AB - Evoked potentials and responses of single hypoglossal neurons were recorded in response to electrical stimulation of the labyrinth. In addition, the spontaneous electrical activity of hypoglossal neurons was significantly modified in response to ipsi- and contralateral static tilt of the whole animal and thermic stimulation of the labyrinth. The experiment showed that the labyrinth modulates the electrical activity of hypoglossal neurons with phasic inputs in response to ampullar stimulation and with tonic inputs in response to macular stimulation. The vestibular phasic influence of hypoglossal neurons represents the most adequate functional pattern to obtain a quick, short lasting response of the tongue muscles instantly modifiable with every abrupt head displacement. On the contrary, the vestibular tonic influence of hypoglossal neurons represents the most adequate functional pattern to obtain not only adjustment but also maintenance of the muscular lingual response to static displacement of the head. PMID- 3342344 TI - Responsiveness of suprachiasmatic and ventral lateral geniculate neurons to serotonin and imipramine: a microiontophoretic study in normal and imipramine treated rats. AB - The suprachiasmatic nuclei (SCN) are a major pacemaker of circadian rhythms in mammals. The SCN receive a direct retinal projection and a second optic input via the ventral lateral geniculate nucleus (vLGN). Both visual pathways mediate the entrainment of circadian rhythms, whereas both the SCN and the vLGN receive serotonergic afferents from the raphe nuclei. We investigated the effects of microiontophoretically applied serotonin (5HT) on SCN and vLGN cells in normal rats and rats chronically treated with the 5HT reuptake blocker imipramine (IMI). In the SCN of both groups over 40% of all recorded cells (N = 80) responded to 5HT with a dose-dependent suppression of their spontaneous or glutamate-evoked discharge, while twenty percent were tonically light-responsive. Except for one cell with an inconsistent 5HT response, none of the visual SCN neurons were 5HT sensitive. In the vLGN of normal and IMI-treated rats about 60% of the cells recorded (N = 42) were inhibited by 5HT. In IMI-treated rats a few cases of excitation by 5HT were encountered in the vLGN. Visual as well as non-visual vLGN cells were responsive to 5HT. Microiontophoretic application of IMI resulted in suppression of electrical activity in both brain regions and enhanced the response induced by 5HT. Chronic IMI-treatment produced a significant increase in the sensitivity of cells in the SCN and vLGN to iontophoresed 5HT, without affecting the relative magnitude of the inhibition. The recovery from 5HT-induced inhibition was slow in these animals. Interestingly, the spontaneous discharge rate of both 5HT-sensitive and 5HT-insensitive SCN and vLGN cells was significantly lower in the imipramine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342345 TI - Computerized readability analysis of written materials. PMID- 3342346 TI - There's a computer in the curriculum! PMID- 3342347 TI - Collaboration. A computer-supported accreditation site visit. PMID- 3342348 TI - A legal checklist for O.R. supervisors. PMID- 3342350 TI - Lavage fluid in sexual-assault examination. PMID- 3342349 TI - Osteotomy cervical spine under local anaesthesia. PMID- 3342352 TI - Nonvalidated food allergy tests. PMID- 3342351 TI - Asbestos: promotion or prohibition? PMID- 3342353 TI - AIDS in the OR: a surgeon's view. PMID- 3342354 TI - AIDS in the pre-AIDS era. PMID- 3342355 TI - Death and brain death: a new formulation for Canadian medicine. Canadian Congress Committee on Brain Death. PMID- 3342356 TI - Manitoba's methadone program: the first 15 years. PMID- 3342357 TI - Drug reactions: unravelling idiosyncrasy. PMID- 3342358 TI - Reducing tobacco consumption: public policy alternatives for Canada. AB - The costs of smoking are extensive, not only in fiscal terms but also in terms of human suffering. A review of several major public policies reveals that concerted efforts by all levels of government and by the public can have an effect on the rate of consumption of tobacco. Specifically, increases in price through taxation, anti-smoking messages, restrictions on smoking behaviour and increased public pressure are effective in reducing smoking. Serious joint efforts in the area of public policy should be pursued to control the effects of this hazardous practice in Canada. PMID- 3342359 TI - Influence of estrogen receptor status on dietary risk factors for breast cancer. AB - It has been suggested that the relation between diet and breast cancer may depend on estrogen receptor (ER) status. We examined the responses to a self administered questionnaire on frequency of consumption of various foods by 493 women with breast cancer (160 with ER-negative tumours and 333 with ER-positive tumours) and 527 controls whose menopausal status was known. Analysis of the reported consumption of foods selected for their fat or carotene content showed no clear distinction in dietary factors between the ER-negative and ER-positive groups. Frequent consumption of meat fats generally increased the risk of both ER negative and ER-positive tumours; there were no clear trends in risk associated with vegetable consumption for either ER group. Fish was the only item affecting the risk for ER-negative and ER-positive tumours differently, frequent consumption reducing the risk for the former (p = 0.02). The results do not support the hypothesis that ER status influences the relation between dietary fat consumption and risk of breast cancer. PMID- 3342360 TI - Endemic institutional salmonellosis due to lactose-fermenting Salmonella newport in Nova Scotia. AB - We report two outbreaks of salmonellosis due to lactose-fermenting Salmonella newport in a Halifax nursing home in August 1983 and July 1986 that we believe were related. The relative rarity of this serotype and other epidemiologic evidence suggest that the organism was endemic in the institution for at least 3 years. Persistent carriers as well as ill and convalescing patients presumably were responsible for propagation of the outbreak. We recommend adequate microbiologic follow-up of infected residents and implementation of surveillance and infection control measures for nursing homes and special care institutions. PMID- 3342361 TI - Dimenhydrinate: evidence for dependence and tolerance. PMID- 3342363 TI - Dear Doctor: Canada's medical columnists make house calls to the nation. PMID- 3342362 TI - Lack of communication cited after patient dies during procedure. PMID- 3342364 TI - My other career. PMID- 3342365 TI - Can drugs that cause adverse reactions be saved? PMID- 3342366 TI - Immunogenicity of a polyvalent melanoma antigen vaccine in humans. AB - Fifty-five patients with Stage II (36 patients) or Stage III (19 patients) malignant melanoma confirmed histologically received adjuvant immunotherapy with a polyvalent melanoma antigen vaccine to evaluate toxicity and immunogenicity. There was no toxicity. Antibody and/or cellular immune responses to melanoma were induced more frequently in Stage II (36 patients [69%]) than Stage III (19 patients [53%]) disease. The ability of different immunization schedules, alum, or pretreatment with low-dose cyclophosphamide to potentiate immunogenicity was compared after 2 months of immunization. Immunization biweekly with a fixed intermediate dose of vaccine was more immunogenic than immunization weekly with escalating vaccine doses. Alum increased the intensity of cellular responses slightly, whereas pretreatment with cyclophosphamide augmented both the incidence and intensity of cellular immune responses slightly. However, these changes did not reach statistical significance. There was a reciprocal relationship between the induction of humoral and cellular immune responses. These results show that (1) active immunotherapy with a polyvalent melanoma vaccine is safe in patients with minimal disease, (2) the vaccine augments immunity to melanoma in many, but not all, patients, and (3) several immunization strategies failed to potentiate immunogenicity significantly. PMID- 3342367 TI - Intralesional interferon-alpha therapy in advanced malignant melanoma. AB - Fifty-one evaluable patients with histologically proven metastatic melanoma and at least one skin metastasis were treated intralesionally with interferon-alpha (IFN-alpha). Twenty-six of the patients were given highly purified natural IFN alpha 6 Mio. IU three times per week. Twenty-five patients were given 10 Mio. IU three times per week of a recombinant IFN-alpha 2b (rIFN-alpha 2b). All patients were examined for systemic and local responses to this treatment. The systemic responses consisted of nine objective remissions, each of which lasted from 2 to 18 or more months. There were 24 complete or partial local responses. Forty-two of the 51 patients had at least two skin metastases so that IFN-injected and noninjected tumor sites could be compared. The difference between systemic and local efficacy was highly significant statistically (P = 0.0004). The results show that IFN-alpha has clinically observable antitumor activity in malignant melanoma. PMID- 3342368 TI - T-antigen. A prognostic indicator of high recurrence index in transitional carcinoma of the bladder. AB - Forty biopsies from 36 patients with bladder tumors were tested for T-antigen (TAg) expression on tumor cells on sections untreated or treated with neuraminidase; a 37.5% of tumors showed abnormal expression of TAg either as an aberrant expression, or absence of this antigen after removing sialic acid. These changes were not well correlated with histologic signs of anaplasia or infiltration, nor with other biologic properties of tumor cells such as the expression of blood group antigens (ABH). However, a practical utility of TAg in the study of bladder tumors, is suggested by the analysis of those biopsies with low-grade low-stage tumors, on which the abnormal expression of TAg was more discriminatory than the ABH changes in defining those patients suffering tumors with a particular aggressiveness. Circulating antibody titer was also investigated in 20 patients but all of them displayed titers in the normal range, with independence of the results observed in their corresponding bladder biopsies. PMID- 3342369 TI - Treatment of inflammatory breast cancer with combination chemotherapy and mastectomy versus breast conservation. AB - Twenty-six consecutive patients with nonmetastatic inflammatory breast cancer (IBC), were treated in a single institution using the same protocol, and all were followed for at least 48 months. The first phase of treatment consisted of two monthly cycles of combination chemotherapy with Adriamycin (Adria Laboratories, Columbus, OH), vincristine, cyclophosphamide and 5-fluorouracil. Local treatment was then undertaken using in all cases a cobalt 60 beam to deliver 45 Gy to the entire mammary gland and lymph-draining areas. Local treatment was completed either by mastectomy, or by conservation of the breast and interstitial irradiation of the primary tumor site. Chemotherapy was resumed after completion of local treatment for a total of 6 cycles. Metastatic disease occurred in 19 of 26 patients from 8 to 55 months; five patients are alive and free of disease from 48 to 81 months. Failure to control local disease or local recurrences was noted in two of ten patients undergoing mastectomy, and in seven of 13 patients with conservation of the breast. While this difference is not statistically significant we concluded that methods of breast conservation which limit the high dose volume to the tumor site do not assure local control in IBC. The median disease-free survival and overall survival of 12 and 31 months, respectively, are not satisfactory. Better systemic treatment is needed. PMID- 3342370 TI - Long-term comparison of results of a drug sensitivity assay in vitro with patient response in lymphatic neoplasms. AB - A short-term differential staining cytotoxicity (DiSC) assay was used to assess the sensitivity of tumor cells in vitro from patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma to various cytotoxic drugs. The results have been correlated with drug sensitivities of the tumors in vivo. The chemosensitivity in vitro of eight patients with CLL was observed for 12 to 42 months. In 44 cases the assay correctly predicted seven sensitive and 30 resistant tumors (84% positive correlations). There were six false predictions of sensitivity and one false prediction of resistance. Repeated testing of patients receiving treatment revealed significant and progressive development of drug resistance, while serial tests on untreated patients with CLL gave unaltered results. The development of cross-resistance to structurally related drugs was observed after treatment and many samples showed a high level of cross resistance. However, teniposide showed greater activity than etoposide, and mitoxantrone showed greater activity than the anthracyclines. The high level of agreement between laboratory and clinical results suggests that the DiSC assay may have a useful place (1) in guiding the clinician in the selection of drugs for chemotherapy and (2) in giving an added indication of prognosis for an individual with a lymphatic neoplasm. PMID- 3342371 TI - External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer. AB - One hundred fifty-nine patients with unresectable but localized pancreatic cancer, as defined at exploratory laparotomy, were treated at the Mayo Clinic between February 1974 to April 1985. Postoperative therapy consisted of 4000 to 6000 cGy external beam irradiation (XRT) alone in 122 patients or 4500 to 5500 cGy XRT in combination with an intraoperative electron boost in 37. In addition, 132 (both groups) received 5-fluorouracil (5-FU) chemotherapy. Local control (LC) at 1 year was 82% with XRT + intraoperative radiation therapy (IORT) versus 48% with XRT and 66% versus 20% at 2 years respectively (P less than 0.0005). Due to the high incidence of hematogenous and/or peritoneal spread in both groups (abdominal failure in 54 and 56% of patients at risk), the decreased frequency of local progression did not translate into an improved survival. Neither median nor long-term survival of the two treatment groups (XRT versus XRT + IORT) was statistically different (median 12.6 months versus 13.4 months, P = 0.25). With tumor arising in the head of the pancreas, survival at 2 years was 18% as opposed to 0% for other locations (P less than 0.01). On the basis of a Cox multivariate analysis, no other treatment or prognostic factor significantly altered survival. Until the problem with systemic failure (usually abdominal) can be resolved, the median and long-term survival of patients with pancreatic carcinoma is likely to remain unchanged. Since IORT appears to improve local control, we will continue to utilize IORT in phase 1, 2 studies which also attempt to decrease the incidence of abdominal failures. Even with IORT + XRT combinations, the incidence of local progression is excessive and radiation dose modifiers need to be evaluated. PMID- 3342372 TI - Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation. AB - One thousand three hundred seventy-nine nasopharyngeal carcinoma (NPC) patients were treated from March 1958 to December 1978. Twenty-two percent had stage I or II and 78% Stage III or IV had lesions. Two hundred twenty-Kv radiographs were used before 1960; and telecobalt was used from 1961 to 1978. Factors influencing the 5-year survival rate favorably are youth of patient, being female, pathologic condition (poorly differentiated carcinoma, 45.1% versus adenocarcinoma, 13%), stage (Stage I, 86%, Stage II, 59.5%; Stage III, 45.8%; Stage IV, 29.2%), decade admitted for treatment in the past (31% in the 1950s, 48.6% in the 1970s), total dose delivered to the nasopharynx (40 to 49 Gy, 46%; 70 to 79 Gy, 54.1%; 90 Gy or more, 64%) and prophylactic radiation to the neck regions (with prophylactic irradiation, 53.8%, without prophylactic irradiation, 23%). This implies that prophylactic radiation of the neck is crucial even without positive clinical metastasis. For those who have a residual tumor in the primary site when 70 Gy has been delivered, the total dose may be boosted to more than 90 Gy with the cone-down technique or on basis of adding 20 Gy to the dose at which the primary lesion disappeared grossly. The common postirradiation complications are: radiation myelitis, trismus, and otitis media. Because disease recurred in some patients after the fifth year, NPC patients should be followed for at least 10 years. PMID- 3342373 TI - Elevated serum neuron-specific enolase in patients with malignant pheochromocytoma. AB - Neuron-specific enolase (NSE), an isomer of glycolytic enzyme enolase, is found exclusively in neuroendocrine cells and in neuroendocrine tumors in a considerably large quantity. Circulating levels of serum NSE were measured by radioimmunoassay in 24 normal adults, 23 patients with benign pheochromocytoma, three patients with malignant pheochromocytoma, and seven patients with medullary thyroid carcinoma. The mean serum NSE in normal adults was 5.8 +/- 1.3 ng/ml (mean +/- standard deviation [SD], and the range was 3.8 to 8.9 ng/ml). It also was normal in patients with benign pheochromocytoma (5.7 +/- 1.8 ng/ml; range, 2.2 to 9.3 ng/ml). However, serum NSE was elevated significantly (17.2 +/- 7.2 ng/ml; range, 10.4 to 27.3 ng/ml) in all three patients with malignant pheochromocytoma (P less than 0.01). In patients with medullary thyroid carcinoma the serum NSE remained within normal limits (5.5 +/- 1.7 ng/ml; range, 3.9 to 8.2 ng/ml). These results suggest that serum NSE might be a useful marker for screening of malignant pheochromocytoma. PMID- 3342374 TI - The histologic diagnosis of adenocarcinoma in situ and related lesions of the cervix uteri. Adenocarcinoma in situ. AB - Seventy-two cases of in situ adenocarcinoma (AIS) of the cervix were reviewed. Forty-five cases had associated cervical intraepithelial neoplasia and 20 cases had changes of wart virus infection. Five cases had associated microinvasive squamous cell carcinoma and one cases showed frankly invasive squamous cell carcinoma (SCC). Of the 72 cases, 41 showed an endocervical type of AIS and three cases an endometrioid type. There was no case of pure intestinal type AIS. Twenty eight cases showed a mixed pattern. Architectural patterns characterized by tunnel clusters, cribriform glands, glandular budding and papillary formations were assessed. Most cases showed varying combinations of these patterns but in ten cases significant changes were absent. Both cellular apoptosis and mitotic activity were seen in varying degrees in all cases of AIS. The significance of these and other features of AIS are discussed as well as the conditions involved in the differential diagnosis. PMID- 3342375 TI - Detection of proliferative cells in dysplasia, carcinoma in situ, and invasive carcinoma of the uterine cervix by monoclonal antibody against DNA polymerase alpha. AB - The distribution of DNA polymerase alpha-positive cells in neoplasia of the uterine cervix and in normal cervical epithelium was studied using a monoclonal antibody against DNA polymerase alpha. The positive cells were found only in the parabasal layer of normal cervical epithelium and only in the nonkeratinized areas of the cancer nests of invasive keratinizing carcinoma. Most cells in cancer nests of an invasive nonkeratinizing carcinoma were found to be DNA polymerase alpha-positive. In cases of mild or moderate dysplasia DNA polymerase alpha-positive cells were found only in the lower half of the epithelium. DNA polymerase alpha-positive cells in severe dysplasia to carcinoma in situ were distributed throughout the full thickness of the epithelium. The percentages of DNA polymerase alpha-positive cells in mild or moderate dysplasia, severe dysplasia to carcinoma in situ, and invasive carcinoma were 32.2%, 45.7%, and 53.7%, respectively. The authors previously developed immunohistochemical methods for detecting DNA polymerase alpha by monoclonal antibody that allowed the proliferative activity of cells in normal and neoplastic tissues to be estimated. PMID- 3342376 TI - Renal carcinoma. Reevaluation of prognostic factors. AB - The purpose of the study documented in this article was to reevaluate the prognostic value of tumor size, cytologic grading, and histologic pattern in patients with renal carcinoma. One hundred and eighty-six renal carcinomas were histologically graded. In 175 cases clinical follow-up information was obtained. It was found that for 5 years of survival there are essentially two prognostic groups. The first group includes tumors with solid patterns and clear cells, tumors with granular cells without field, and tumors with a papillary pattern or oncocytic cells. This group has a much better than the second group of tumors, which have either a large number of granular cells with field or a sarcomatoid or stratified pattern. It was also observed that for prognostic evaluation the histologic pattern was a better parameter than size and cytologic grading. PMID- 3342377 TI - Diagnostic excision of the Rosenmuller's node. Screening for occult metastases before elective regional lymph node dissection in patients with lower limb melanoma? AB - Elective radical groin dissection was performed on 297 consecutive patients with high-risk melanoma of the leg, Anderson Stages I, IIA, IIIA. By separate histologic examination of the so-called "Rosenmuller's node," the other inguinal, and the external iliac lymph nodes, the diagnostic excision of the Rosenmuller's node was tested as a suitable mode of screening for metastases before a planned elective regional lymph node dissection. Eighty patients (27%) presented with what was histologically determined to be occult groin metastases. Rosenmuller's node was involved in 30 of these cases; in the remaining 50, however, it was not affected; that is, 63% of the cases were false-negative. Thus, the involvement of Rosenmuller's node is not representative of metastases in the other ilioinguinal lymph nodes, but is rather a matter of chance. In women with superficial spreading melanoma the rate of occult lymph node metastases was significantly lower than that in men with melanomas of the other type. Iliac lymph node involvement was observed in 18 patients (22%) depending on clinical stage and depth of invasion of the primary tumor. PMID- 3342378 TI - Controlled and uncontrolled thrombocytosis. Its clinical role in essential thrombocythemia. AB - Only two of 19 patients with spontaneously evolving essential thrombocythemia remained asymptomatic in a 421 patient-month observation. The rest of the patients showed hemorrhagic diathesis (four patients), nonspecific neurological semiology (two patients), and occlusive vascular illness in cerebral, myocardic, arterial, and often multiple locations (total, 12 patients). Peripheral neuropathy was found in five of 10 patients studied. In this series the incidence of cerebral ischemia in the uncontrolled condition was 180 times higher than the epidemiologic expectancy in a population not affected by the disorder. Of 35 ischemic attacks, 22 occurred when the platelet count was more than than 1000 X 10(9)/l, 13 when the count ranged from 650 to 990 X 10(9)/l, and none occurred at counts of less than 650 X 10(9)/l. In contrast, therapeutic control of the thrombocytosis caused all complications to disappear. These findings point out the danger of the natural course of the illness and justify active therapy. At the same time they call into question some of the most commonly used criteria in the diagnosis of essential thrombocythemia. PMID- 3342379 TI - The influence of obesity and age at diagnosis on the estrogen receptor status of breast cancers. Perimenopausal predominance of estrogen receptor negative tumors. AB - Estrogen receptor (ER) status of 763 primary breast cancers was analyzed by host age and obesity. Tumors from women less than 40 years of age were found to be ER negative (ERN) predominantly. Tumors from women greater than 40 years of age demonstrated increasingly higher median values for ER protein and were ER positive (ERP) predominantly except for those presenting among nonobese women 45 to 49 years of age and obese women 50 to 54 years of age. Tumors from these two subgroups were more frequently ERN than those from women of similar habitus who were immediately younger (P less than 0.05) or older (P less than 0.02), or than those from women of the same age and differing obesity status (45 to 49 years of age P less than 0.01; 50 to 54 years of age P greater than 0.05). This altered pattern of estrogen binding in perimenopausal tumors likely results from the hormonal changes of the menopausal and late premenopausal years. Recognition of their varied patterns of estrogen binding should assist in understanding the behavior of these perimenopausal tumors and in the selection of optimal antitumor therapy for their hosts. PMID- 3342380 TI - Intraoperative photodynamic therapy for retroperitoneal sarcomas. AB - A pilot study was done to determine the feasibility of adjuvant photodynamic therapy (PDT) in recurrent retroperitoneal sarcomas. Ten patients, who had recurrences after conventional methods of treatment, had repeated resections of the tumor and intraoperative photodynamic treatment to the tumor bed. The methods and equipment used are detailed. In eight of ten patients, a complete resection was possible, and two patients are alive without recurrence at 28 and 24 months. There were no complications from the therapy. Tumors elicited red fluorescence, which helped in identifying residual tumor areas. Adjuvant PDT is a feasible alternative although its effectiveness should be evaluated further. PMID- 3342381 TI - Evaluation of recent trends in cancer mortality and incidence among blacks. AB - Recent trends in the cancer incidence, mortality, and 5-year survival rate for the black population were evaluated using the available national data up to 1981. Blacks have the highest overall age-adjusted cancer rates in both incidence and mortality of any US population group. The overall cancer incidence rates for blacks rose 17%, while for whites it increased 13% from 1969 to 1981. The rate in black men has increased 22.9%, while the rate in black women has increased 13.1%. The overall increase is the result of increases in cancers of the lung, prostate, colon-rectum, and esophagus. The age-specific incidence of lung cancer reflects the decrease of its incidence in those between 20 and 40 years of age because of the change in smoking habits after the Surgeon General's report on smoking. The overall cancer mortality rates for blacks increased 39% during the period. Lung cancer had the highest mortality rate, having increased more than 77.8% since 1969. This trend greatly reflects the recent increase in lung cancer incidence among black women. The overall 5-year cancer survival pattern for blacks was almost unchanged from 1973 to 1981, while whites had slightly higher survival rates during this period. However, blacks had substantial increases in survival rates for cancers of the esophagus and bladder during the period. PMID- 3342382 TI - Descriptive epidemiology of intestinal cancer in Italy. AB - Trends in the death rates from cancers of the intestine (including colon and rectum) in Italy from 1956 to 1981 were analyzed with a standard cross-sectional approach and a log-linear age/period/cohort model. In both sexes there were steady increases in mortality rates between the middle 1950s and the middle 1970s, chiefly explainable in terms of cohort effects. This was followed by a leveling off and stabilization, starting from the younger age groups and more evident in women. The analyses of the geographic distribution of intestinal cancer mortality in the 95 Italian provinces during 1975 to 1977 showed higher rates in the north of the country and in large urban concentrations, and a bimodal distribution of mortality rates, whose minimum corresponded to a distinct north/south separation. Trend surface models fitted to intestinal cancer standardized mortality ratios showed a high determination coefficient even for the simplest models. Residuals, corresponding to outliers, were scattered in a few northern and central areas. In addition, mortality rates for cancers of the intestine in middle age people were considered according to geographic area of birth and residence at death. In both sexes rates of migrant populations were influenced both by area of birth and residence, and, in particular, there was a wide-spread unfavorable effect of residence on migrants from the South to the North (the major migrant flux in Italy). The temporal and geographic variations in intestinal cancer rates observed in this study indicate that Italy may well be a particularly interesting situation for etiologic investigations of colorectal cancers. PMID- 3342383 TI - Descriptive epidemiology of thyroid cancer in Hawaii. AB - Data were analyzed from 1110 thyroid cancer cases between 1960 and 1984 identified by the Hawaii Tumor Registry, a population-based Statistics, Epidemiology and End Results (SEER) participant covering the entire state of Hawaii. Incidence rates for men and women were relatively stable during this 25 year period. The overall age-adjusted rates were 8.1 per 100,000 for women and 3.1 per 100,000 for men. There was a significant variation in incidence on the basis of ethnicity, with the highest rates for women occurring in Filipinos (18.2 per 100,000) and for men in Chinese (6.3 per 100,000). A comparison of different populations around the world showed that Hawaii has some of the highest reported incidence rates for thyroid cancer. In addition, a comparison of ethnic-specific incidence rates for groups living in Hawaii with people of the same ethnic backgrounds living in other geographic areas showed that Hawaii residents generally have much higher rates, suggesting that environmental influences are responsible for the unusually high rates in Hawaii. PMID- 3342384 TI - Cytological diagnosis by fine needle sampling without aspiration. PMID- 3342385 TI - Persistent chromosome damage induced by localized radiotherapy for lymphoma. AB - A fibroblast culture was established from a lymph node biopsy of a patient with non-Hodgkin lymphoma, 9 months after chemotherapy and intensive therapeutic x irradiation of the area. In contrast with blood and bone marrow, which were chromosomally normal, all cells of the lymph node were chromosomally abnormal, with numerous clones having multiple structural abnormalities. Numerical abnormalities (trisomies and monosomies) were not found. Structural abnormalities included translocations, terminal deletions, and pericentric inversions, with an excess of centromeric breakpoints being the only apparent deviation from a random distribution of breakpoints. None of the rearrangements associated with malignant lymphoma were seen, indicating that the chromosome abnormalities in the lymph stroma were radiation-associated, not disease-associated. These acquired changes may be a cause of additional malignant transformation. PMID- 3342386 TI - Cytogenetic findings in a supratentorial ependymoma. AB - Cytogenetic studies on a supratentorial ependymoma from a 3-year-old girl showed a t(10;11;15)(p12.2;q13.1;p12) and loss of one X chromosome. To our knowledge, this is the first ependymoma reported with relatively simple karyotypic changes. PMID- 3342387 TI - Multiple karyotypic rearrangements, including t(X;18)(p11;q11), in a fibrosarcoma. AB - The tumor stem line of a soft tissue fibrosarcoma, histologic malignancy grade III, had 43 chromosomes with several clonal chromosome aberrations, including the three balanced translocations t(X;18)(p11;q11), t(2;15)(p23;q26), and t(7;22)(q11;q13), two partly identifiable marker chromosomes, der(3)dic(3;?)(p11;?) and der(5), one small marker of unknown origin, and loss of one chromosome #11, #18, #19, and #21. PMID- 3342388 TI - Chromosome changes in a prostatic leiomyosarcoma. PMID- 3342389 TI - Translocation 2;8 in a congenital rhabdomyosarcoma. PMID- 3342390 TI - Vitamin B6 metabolism in McA-RH7777 cells. AB - The metabolism of vitamin B6 in McA-RH7777 cells has been characterized with respect to pyridoxal 5'-phosphate (PLP) levels, and the activities of pyridoxine (PN) kinase (EC 2.1.7.35) and pyridoxine 5'-phosphate (PNP) oxidase (EC 1.4.3.5). PLP levels (12.4 +/- 4.4 ng/mg protein) were at the lower end of the range found for Morris hepatomas, carcinogen-induced rat hepatomas, and liver from rats fed a PN-deficient diet. PN kinase activity was about one-third of that found in normal rat liver. PNP oxidase appeared to be absent in high-speed supernatants of homogenates prepared from McA-RH7777 cells. The absence of PNP oxidase was supported by enzymatic and immunological data. These findings resemble those found previously for Morris hepatoma 7777. In contrast to rat liver, such preparations caused little or no release of volatile counts upon incubation with either [3H-C4']PN or [3H-C4']PNP. High-speed supernatants of homogenates prepared from both McA-RH7777 cells and Morris hepatoma 7777 were very much less capable than similar preparations from rat liver in converting [G-3H]PN to PLP and pyridoxamine 5'-phosphate. Despite the apparent absence of PNP oxidase, intact confluent or log-phase McA-RH7777 cells were capable of converting [G-3H]PN to PLP and pyridoxamine 5'-phosphate. These findings are discussed in terms of tumor nutrition and vitamin B6 metabolism in a rat hepatoma cell line. PMID- 3342391 TI - Sensitization of nitrosourea-resistant Mer+ human tumor cells to N-(2 chloroethyl)-N'-cyclohexyl-N-nitrosourea by mild (41 degrees C) hyperthermia. AB - Experiments were designed to determine whether heat treatment could sensitize nitrosourea-resistant human tumor cell lines expressing a repair system (O6 alkylguanine DNA alkyltransferase; Mer+) capable of removing monoadducts from the DNA of treated cells prior to the formation of lethal interstrand cross-links. Effects of temperatures compatible with systemic hyperthermia were of particular interest, and, consequently, the effect of 1-(2-chloroethyl)-3-cyclohexyl-1 nitrosourea (CCNU) exposure in vitro for 4 h at 37 degrees C was compared with that for 1 h at 41 degrees C followed by 3 h at 37 degrees C. CCNU toxicity was significantly enhanced by heat treatment in the Mer+ HT-29 human colon carcinoma, and in HeLa-S3 and HeLa-CCL2 cell lines [thermal enhancement factor (ratio of CCNU doses required to reduce cell survival to 0.001 at 37 degrees C and 41 degrees C) = 1.3-1.4]. Pharmacokinetic studies indicated that the effect of heat treatment on CCNU toxicity was not attributable to exposure to increased concentrations of reactive species, nor was the enhancement due to a direct effect of heat and/or drug on alkyltransferase activity. A similar enhancement of CCNU toxicity was also observed in a Mer- line, HeLa-MR (thermal enhancement factor = 1.3). Heat-sequencing experiments clearly demonstrate that heat and CCNU must be administered concurrently. Alkaline elution experiments were designed to examine DNA-DNA cross-link formation in Mer+ and Mer- cells exposed to CCNU at 37 degrees C and 41 degrees C, but quantitation of cross-link formation was not possible owing to the persistence of single strand breaks in the DNA of drug treated cells. Nevertheless, collectively the data indicate that thermal enhancement of CCNU toxicity is independent of effects on alkytransferase activity and indicate that hyperthermia could provide an effective strategy for improving the nitrosourea response of resistant Mer+ tumors. PMID- 3342392 TI - Nitrosamine formation from amines applied to the skin of mice after and before exposure to nitrogen dioxide. AB - Skin lipids of mice exposed to NO2 contain lipid-soluble nitrosating agent(s) (NSA) that react in vitro with amines to produce nitrosamines. To test whether this reaction occurs in skin, we exposed mice to 50 ppm NO2 for 4 h and, 20 h later, applied 25 mg morpholine or N-methylaniline to the skin, which was then analyzed for the corresponding nitrosamine. When morpholine was applied, mean N nitrosomorpholine yield was only 0.3 nmol/mouse (not significant). When N methylaniline was applied and mice were killed after 10-40 min, N-nitroso-N methylaniline yield in the skin was 13-21 nmol/mouse of which 87% occurred in the hair. NSA formation when mice were exposed to 6.5 ppm NO2 was only 0.15% of that for exposure to 50 ppm NO2. NSA occurred mostly in surface lipids of the skin and its in vitro reaction to give nitrosamines was not inhibited by alpha-tocopherol. When morpholine was painted and mice were then exposed to 55 ppm NO2 for 30 min, the skins contained 19 nmol N-nitrosomorpholine/mouse, attributed to a direct reaction between NO2 and the amine. We concluded that nitrosamine formation in skin by this direct reaction may be more important than the reaction of amines with NO2-derived NSA. PMID- 3342393 TI - Stimulation of polyadenosine diphosphoribose synthesis by DNA lesions induced by sodium chromate in Chinese hamster V-79 cells. AB - Polyadenosine diphosphoribose [poly(ADP-ribose)] synthesis was stimulated by DNA lesions induced with Na2CrO4 and methyl methanesulfonate (MMS) in Chinese hamster V-79 cells. Na2CrO4 and MMS induced DNA single-strand breaks in a concentration dependent manner; however, the breaks induced by Na2CrO4 were "protein associated" while those induced by MMS were not. MMS stimulated in a dose dependent fashion the synthesis of poly(ADP-ribose) up to 6-fold above the control. Na2CrO4 also induced poly(ADP-ribose) synthesis, but the level of synthesis was less than 3-fold. Control experiments demonstrated that Na2CrO4 treatment of cells did not affect their ability to synthesize poly(ADP-ribose) in response to DNA damage. Treatment of cells with Na2CrO4 and MMS induced more poly(ADP-ribose) synthesis than each agent alone; however, whenever Na2CrO4 was utilized, the breaks required proteinase K to be detected. Following removal of extracellular chromate, the DNA strand breaks induced by 0.2 mM Na2CrO4 were repaired quickly during the first hour but more slowly for the next 3 h. In the presence of 3-aminobenzamide, an inhibitor of poly(ADP-ribose) synthesis, the repair of DNA breaks was reduced. These results suggest that DNA protein associated breaks produced by Na2CrO4 were recognized by poly(ADP-ribose) polymerase and that there are differences in poly(ADP-ribose) synthesis in response to Na2CrO4 and MMS. The results also suggest that the repair of breaks induced by Na2CrO4 are associated with poly(ADP-ribose) synthesis, but perhaps because most of these breaks are protein associated, there is less stimulation of poly(ADP-ribose) synthesis. PMID- 3342394 TI - Enhancement of cytogenetic damage and of antineoplastic effect by caffeine in Ehrlich ascites tumor cells treated with cyclophosphamide in vivo. AB - Enhanced cytogenetic damage by cyclophosphamide (CP) was observed when Ehrlich ascites tumor cells were exposed in vivo to nontoxic concentrations of caffeine. One h before i.p. injection of 5-bromodeoxyuridine adsorbed to activated charcoal Ehrlich ascites tumor-bearing mice treated i.p. with CP appear to have a dose dependent increase in sister chromatid exchange rates and cell division delays. Caffeine increased the survival time of the Ehrlich ascites tumor-bearing mice treated with CP and markedly reduced the ascitic volume. Therefore, the in vivo antitumor effect by CP in conjunction with caffeine appears to correlate well with the in vivo synergistic effect on cytogenetic damage caused by the combined CP plus caffeine treatment. PMID- 3342395 TI - High-frequency generation of altered Mr 70,000 env glycoproteins in N-methyl-N' nitro-N-nitrosoguanidine-treated murine tumor cells. AB - In previous studies we have characterized variant clones established following treatment of mouse Eb lymphoma cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Some of these clones were impaired in tumorigenicity due to an increased immunogenicity (tum- phenotype). In this paper we investigated the mutagenic effect of MNNG on cell surface molecules. The results show that retroviral Mr 70,000 glycoprotein (gp70) antigens undergo extensive alterations following MNNG treatment. In five of five mutant clones analyzed, the two-dimensional gel electrophoretic patterns of gp70 antigens were altered in comparison to the parental Eb cells. Peptide mapping analysis of immunoprecipitated gp70 molecules using three different enzymes revealed detectable changes in amino acid sequence in three of five mutant clones. In contrast, no alterations were detected in H 2Kd and H-2Dd antigens of the same clones. The gp70 antigens expressed by mutant clones could be resolved in three distinct clusters. Only one cluster induced antibodies in the syngeneic host. When genomic DNAs of MNNG clones were investigated by Southern blot analysis using a gp70-specific probe, an additional 4.5-kilobase hybridizing band could be detected that was not present in parental Eb cells and 5'-azacytidine-treated Eb clones. Collectively, our results show that gp70 antigens and genes are affected by MNNG treatment with high frequency. The possible role of structurally altered gp70 molecules in the immunogenicity of mutagenized tumor cells is discussed. PMID- 3342396 TI - Reduced genomic 5-methylcytosine content in human colonic neoplasia. AB - DNA methylation appears to play an important role in both physiological and experimentally modified gene expression, and alterations in DNA methylation have been described in animal tumor models and in transformed cells and tumor cell lines. However, there have been comparatively few reports on DNA methylation in primary human malignancies, and these reports are somewhat contradictory. While individual genes have shown hypomethylation in colon cancer and premalignant adenomas as well as in lung cancer, other genes have shown increased methylation, and absolute measures of 5-methylcytosine content have shown decreases in malignancies but not in premalignant adenomas. We have used a sensitive quantitative measurement of 5-methylcytosine content by high performance liquid chromatography revealing an unequivocal hypomethylation of tumor DNA. An average of 8 and 10% reduction in genomic 5-methylcytosine content was seen in apparently all colon adenomas and adenocarcinomas, respectively, and there was no significant difference between benign and malignant tumors. This is a substantial quantitative alteration and suggests a pervasive abnormality in the control of DNA methylation. Surprisingly, three patients with the highest 5-methylcytosine content in their normal colon appear to have a germline predisposition to cancer (Lynch syndrome). PMID- 3342397 TI - Antitumor activity and hematotoxicity of a new, substituted dihydrobenzoxazine, FK973, in mice. AB - FK973, a new, substituted dihydrobenzoxazine (11-acetyl-8-carbamoyloxymethyl-4 formyl-14-oxa-1,11- diazatetracyclo[7.4.1.0.0]tetra-deca-2,4,6-trien-6,9-diyl diacetate), was obtained by chemical modification of a novel antibiotic which was isolated from the fermentation products of Streptomyces sandaensis No. 6897. FK973 had cytotoxic effects against in vitro cultured human and murine tumor cells. FK973 in doses of 0.032-5.6 mg/kg (i.p.) had stronger antitumor activities and higher chemotherapeutic ratio than mitomycin C against such murine ascitic tumors as P388 and L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma of ovarian origin, Colon 26 carcinoma, Ehrlich carcinoma, and MH134 hepatoma. In tests against murine and human solid tumors implanted s.c. in normal mice and nude mice, respectively, FK973 (i.v.) inhibited growth of murine tumors (M5076 sarcoma, Colon 38 carcinoma, B16 melanoma, and Lewis lung carcinoma) by 66-100% and human tumors (LX-1 lung, MX-1 mammary, and SC-6 stomach carcinoma) by 84-99%. In studies with drug-resistant P388 leukemia, FK973 was also effective against vincristine-resistant P388, moderately effective against mitomycin C (MMC)- and adriamycin-resistant P388, and partially effective against cyclophosphamide resistant P388 cells in mice. Leukopenic effects of FK973 and MMC in mice were comparable at doses which gave antitumor activity almost equally. FK973 had no effect on the numbers of platelets and red blood cells, whereas MMC markedly decreased both. FK973 decreased the numbers of colony forming units in spleen and in culture and the effect was less than that of MMC. Therefore, FK973 may give weaker myelosuppression than MMC. The results suggest that FK973 will be a beneficial drug for the treatment of cancer. PMID- 3342398 TI - Use of oligodeoxynucleotides containing O6-alkylguanine for the assay of O6 alkylguanine-DNA-alkyltransferase activity. AB - A sensitive assay procedure was developed for the measurement of the activity of mammalian O6-alkylguanine-DNA-alkyltransferase. The procedure utilized oligodeoxynucleotides containing O6-methylguanine as substrates for the reaction. The oligodeoxynucleotides were end labeled with 32P by the reaction with polynucleotide kinase and [gamma-32P]ATP and allowed to react with organ or cell extracts containing the alkyltransferase. The unmethylated product which was formed was separated from the substrate by reverse-phase high-pressure liquid chromatography. Since the repair by the alkyltransferase is bimolecular, the second order rate constants for the reaction between the labeled oligomer and repair protein from several different sources were determined. The amount of alkyltransferase present was then calculated from the amount of product formed and the appropriate second order rate constant for the reaction. Excellent agreement was obtained between the alkyltransferase levels determined in this procedure and those measured by conventional assay procedures in a variety of cell lines having both high and low activity. The method also gave results in good agreement with other assay procedures for a number of rat tissues, although a few tissues gave anomalous results owing to a high level of nuclease activity which degraded the substrate. This method should prove useful for the measurement of alkyltransferase activity in samples in which the activity is very low or the amount of material available is limited. PMID- 3342399 TI - Transfer by pro gene transfection of tumor promoter-sensitive phenotype to promotion-insensitive JB6 cells. AB - Transfection of activated promotion sensitivity genes (pro genes) confers on insensitive (P-) cells susceptibility to induction of anchorage-independent growth by tumor-promoting phorbol esters. Promotion-sensitive (P+) JB6 cell variants, from which activated pro-1 and pro-2 were cloned, respond to 12-O tetradecanoylphorbol-13-acetate (TPA) and various nonphorbol tumor promoters with anchorage-independent transformation that is irreversible 60-80% of the time. Anchorage-independent (Tx) clonal lines derived from these TPA-induced agar colonies were also tumorigenic in nude mice. This report has addressed the question of whether the phenotypes associated with parental P+ cells are transferred by transfection of activated pro-1 and pro-2. Clonal lines were established after transfection of JB6 P- cells with activated pro-1 or pro-2, induction of anchorage-independent colony formation by TPA, and growth of individual agar colonies to yield clonal transfectant lines. The lines so derived from transfected populations included Tx, P+, and P- lines, reflecting irreversible neoplastic transformation and greater and lesser degrees of preneoplastic progression, respectively. The anchorage-independent transfectants were found to be tumorigenic. Since untransfected P- cells subjected to the same single-cycle TPA treatment and cloning in agar yielded no anchorage-independent and few P+ transfectants, the appearance of P+ and Tx transfectants after pro-1 and pro-2 transfection is therefore likely to be due to the transfected pro genes. Indirect assay of pro gene uptake by quick-blot hybridization of transfectant cell DNA with the vectors into which pro genes had been cloned confirmed the association of transferred P+ and Tx phenotypes with the presence of the transfected DNA. Finally, assay of the sensitivity of P+ pro-1 and pro-2 transfectants to transformation by TPA at various concentrations showed that transfection with pro-1 or pro-2 conferred about equal responses that were somewhat lower than those observed with parental P+ controls. Taken together these data indicate that promotion-insensitive JB6 cells need only an activated pro gene and TPA exposure to become neoplastically transformed. PMID- 3342400 TI - Blood flow and venous pH of tissue-isolated Walker 256 carcinoma during hyperglycemia. AB - Hemodynamic (blood flow rate, hematocrit, hemoglobin concentration, and blood viscosity) and pH responses to glucose (6 g/kg, i.p.) injections were studied in ten Walker 256 carcinoma tumors (0.5-1.8 g) grown in the "tissue-isolated" tumor preparation. A maximum blood flow reduction of 57 +/- 19% (SD) occurred concurrently with an increase in tumor arterial-venous blood pH difference 20-30 min after glucose administration. Tumor venous blood pH dropped significantly by 0.15 +/- 0.07 pH unit to 7.15 +/- 0.01, while systemic blood pH dropped by 0.06 +/- 0.02 pH unit to 7.38 +/- 0.03. Arteriovenous blood pH differences were found to correlate with blood flow rates; however, both the small magnitude of the pH reduction and the immediate blood flow response argue against the hypothesis of increased resistance to flow caused by low pH-stiffened RBC membranes. Significant increases in systemic and tumor efferent whole blood viscosities at 2.25 and 4.5s-1 occurred after glucose administration, while hemoglobin concentrations of systemic and tumor efferent blood increased by as much as 11 +/ 1 and 16 +/- 2%, respectively. Venous to arterial hematocrit and hemoglobin ratios remained unchanged with glucose administration. These data suggest local tumor blood flow reductions are caused by increased viscous resistance to flow within the tortuous microvasculature of tumor, not as a result of low pH RBC rigidity, but rather from other mechanisms such as glucose-mediated RBC rigidity and systemic hemoconcentration. PMID- 3342401 TI - Potentiation of adriamycin cytotoxicity by dipyridamole against HeLa cells in vitro and sarcoma 180 cells in vivo. AB - Dipyridamole (DP) is clinically prescribed for its vasodilating and antiplatelet effects. DP also inhibits nucleoside transport and enhances cytostatic activity of antimetabolites. We obtained evidence for augmentation of the cytocidal effect of Adriamycin (ADM) by DP, both in vitro and in vivo. Nontoxic levels of DP enhanced the cytotoxicity of ADM against HeLa cells, and the 50% effective concentration of ADM was decreased 2.4-fold by DP. DP also increased the activity of ADM in clonogenic assays. Intracellular levels of ADM in the case of concomitant exposure to ADM and DP were 1.5-fold higher than in the case of exposure to ADM alone, determined using high-performance liquid chromatography. Incorporation of ADM into the cells pretreated with DP was also increased (1.4 fold), while the efflux was little affected. The growth of Sarcoma 180 tumors was prominently suppressed by the combination of ADM and DP, compared to findings with ADM alone. DP also prolonged the survival of Sarcoma 180 tumor-bearing mice, when given in combination with ADM. While the enhancement of cytostatic activity of antimetabolites has been attributed to a decrease in utilization of the salvage pathway by DP, our data show that the synergic effects of DP with ADM were the result of increased intracellular levels of ADM. PMID- 3342402 TI - Modulation of the binding of progesterone receptor to DNA by polyamines. AB - Putrescine, spermidine, and spermine are a group of small organic cations, collectively known as polyamines. They are present in all living cells, and their levels are generally increased in tumor cells. Progesterone receptor is a gene regulatory protein that plays a major role in gestation and in hormonal responsiveness of breast cancer. We studied the effects of putrescine, spermidine, 2 lower homologues of spermidine, N1- and N8-acetyl spermidines, spermine, and N1-acetyl spermine on the sedimentation profile and DNA binding of progesterone receptor from rabbit uterus. Progesterone receptor, prepared in hypotonic buffer, sedimented at the 7S region of sucrose gradients. In the presence of 1 mM putrescine, a part of the receptor was converted to a 5S form. In the presence of 1 mM spermidine or 0.25 mM spermine, the receptor was completely transformed to the 5S form. The DNA binding of the 7S form of progesterone receptor was 7 +/- 3%. After incubating this receptor with 1 mM putrescine, 1 mM spermidine, or 0.25 mM spermine, its DNA binding increased to 16 +/- 4, 37 +/- 3, and 44 +/- 5%, respectively. The structural specificity of polyamines in facilitating the DNA binding of progesterone receptor was examined by using two spermidine homologues. The first homologue with one methylene group less than that of spermidine was as effective as spermidine in transforming progesterone receptor. Removal of two methylene groups, however, had a dramatic effect in reducing the efficacy of the resulting molecule to the level of putrescine. Taken together, our results show that natural polyamines are capable of modulating the binding of progesterone receptor to DNA. Since progesterone receptor is associated with the hormonal responsiveness of human breast cancer, polyamine levels in tumor cells might play an important role in the gene regulatory function of progesterone receptor. PMID- 3342403 TI - Role for aldehyde dehydrogenase in survival of progenitors for murine blast cell colonies after treatment with 4-hydroperoxycyclophosphamide in vitro. AB - We have studied the effects of 4-hydroperoxycyclophosphamide (4-HC) on murine hemopoietic progenitors. We found dose-dependent killing and differential sensitivities of colony forming cells with burst forming units-erythrocyte being most sensitive and colony-forming units granulocyte/erythrocyte/macrophage/megakaryocyte most resistant. We also tested the effects of 4-HC on more primitive murine progenitors which were identifiable in our assay system when the addition of interleukin-3 was delayed until Day 7. We found that the sensitivities of the progenitors for blast cell colonies are similar to those of colony-forming units granulocyte/erythrocyte/macrophage/megakaryocyte and that late-appearing blast cell colonies were particularly resistant to 4-HC. In order to study the mechanism of differential sensitivities of murine progenitors to 4-HC, we examined the sensitivities of murine progenitors to 4-HC after brief incubation with diethylaminobenzaldehyde, an inhibitor of aldehyde dehydrogenase. Progenitors for granulocyte/macrophage colonies, granulocyte/erythrocyte/macrophage/megakaryocyte colonies, and blast cell colonies became more sensitive to 4-HC and the differential sensitivities of the progenitors disappeared following this treatment. We also tested the sensitivities of the progenitors to phenylketophosphamide, an analogue of 4-HC which is resistant to inactivation by aldehyde dehydrogenase. Various colony forming units exhibited a similar dose response to this compound. These data indicate that intracellular levels of aldehyde dehydrogenase might play an important role in differential sensitivities of murine colony-forming units to 4 HC. PMID- 3342404 TI - Activation of human squamous cell carcinoma ornithine decarboxylase activity by guanosine triphosphate. AB - Previous studies have demonstrated the presence in mouse epidermal tumors of a structurally and functionally altered ornithine decarboxylase (ODC). In this report, the enzymatic properties of ODC from normal human skin and squamous cell carcinomas are examined. Some tumors contained a more heat stable ODC than the enzyme found in normal skin. GTP stimulated enzyme activity in four of seven tumor extracts tested but had no effect on normal skin ODC. Kinetic analyses indicated that GTP either lowered the apparent Km of tumor ODC for L-ornithine, increased the Vmax, or had both effects, depending on the tumor examined. Gel filtration chromatography of crude tumor extracts indicated the existence of multiple molecular weight forms of ODC, some of which can be activated by GTP and some of which are unaffected by GTP. Some tumors contain both a GTP-activatable and -nonactivatable form of the enzyme. Immunolocalization studies demonstrated the presence within squamous cell carcinomas of cells with a constitutively high level of immunoreactive ODC, a situation never observed in normal skin tissue. These results suggest that some human squamous cell carcinomas contain a functionally altered ODC that may be aberrantly regulated. PMID- 3342406 TI - Conversion from low grade to high grade of rat urinary bladder carcinomas. AB - The present study was conducted to test if low-grade carcinomas induced by a single dose of N-methyl-Nitrosourea (MNU) can be converted to high-grade carcinomas by a second identical dose of the carcinogen. The heterotopically transplanted rat urinary bladder system was used. Four wk after heterotopic bladder transplantation, the recipient male Fischer 344 rats were divided into 2 groups. The first group received 0.25 mg of MNU into heterotopically transplanted rat urinary bladder; the second group (controls) received 0.9% NaCl solution. At week 29 of the experiment, 1/3 of the animals from each group were killed for histological examination of the heterotopically transplanted rat urinary bladders. The remaining animals from each group were divided into 2 subgroups, the first receiving 0.25 mg MNU and the second, 0.9% NaCl solution. All animals were killed at 50 wk of the experiment. MNU-induced carcinomas at week 29 were all of low histological grade and were noninvasive. Longer follow-up without a second carcinogen administration resulted in both an increase in tumor incidence (P less than 0.005) and more tumors per bladder (P less than 0.001), but high grade invasive carcinomas were rare. The second dose of MNU administered at the stage when low-grade carcinomas were prevalent (week 29) resulted in a significant increase in invasive high-grade carcinomas (P less than 0.01). Our data are consistent with the view that the second carcinogen administration induces a new mutation(s) within low-grade carcinomas which leads to invasive carcinomas. PMID- 3342405 TI - Loss of metastatic responsiveness to cell shape modulation in a newly characterized B16 melanoma adhesive cell variant. AB - Repeated selection of an adherent subpopulation from B16-F1 melanoma cells growing in suspension culture on poly(hydroxyethylmethacrylate) [poly(HEMA)] coated plates resulted in the isolation of an adherent variant designated B16 A10. B16-A10 cells are more adherent to poly(hydroxyethylmethacrylate) coated plates than are B16-F1 cells and express an organized actin structure characteristic of highly adherent low metastatic cells as opposed to the poor cytoskeletal organization of B16-F1 cells. Upon growth in suspension, B16-A10 cells do not acquire the enhanced metastatic capability characteristic of B16-F1 cells and they express similar lung colonizing ability irrespective of the culture conditions. The increased metastatic ability of B16-F1 cells in suspension culture has previously been associated with the decreased accessibility of surface proteins to lactoperoxidase catalyzed iodination and with the increased expression of sialylated peanut agglutinin-binding oligosaccharides on these proteins. B16-A10 cells which show no cell shape induced increase in metastatic ability do not undergo alteration in either of these two properties in suspension culture. The absence of these two phenomena on B16-A10 cells grown in suspension indicates that they are interrelated and involved in the increased metastatic ability of B16-F1 cells grown in suspension. PMID- 3342407 TI - Identification of a secreted Mr 95,000 glycoprotein in human melanocytes and melanomas by a melanocyte specific monoclonal antibody. AB - We have isolated a monoclonal antibody, designated HMB-50, that is highly specific for melanomas and melanocyte derived lesions. The antibody recognizes melanomas, neonatal melanocytes, and junctional nevi but does not react with adult melanocytes, dermal nevi, or a variety of non-melanocyte derived neoplasms. In tissue culture, the antibody reacts with five of seven human melanoma lines and neonatal foreskin melanocytes but fails to recognize fibroblasts and a number of different carcinomas. HMB-50 identifies a Mr 95,000 glycoprotein that is released into the growth medium by melanoma cells and neonatal melanocytes in vitro. This molecule is unrelated to antigens recognized by a variety of antimelanoma monoclonal antibodies isolated in other laboratories. The Mr 95,000 glycoprotein has been purified by antibody affinity chromatography and a polyclonal rabbit antiserum raised that exhibits identical specificity to the monoclonal antibody. The Mr 95,000 glycoprotein is rapidly released by melanoma cells (within 60 min) and one line produces relatively large quantities of the molecule (1 microgram/10(6) cells/24 h). The molecule in normal melanocytes differs slightly in electrophoretic mobility compared to its counterpart in melanomas and this difference appears to result from posttranslational modification. PMID- 3342408 TI - Photosensitizing effects of the tricyclic heteroaromatic cationic dyes pyronin Y and toluidine blue O (tolonium chloride). AB - Pyronin Y [3,6-bis(dimethylamino)xanthylium chloride; PY] and toluidine blue O [tolonium chloride; 3-amino-7-(dimethylamino)-2-methyl phenothiazin-5-ium chloride; TB] are cationic dyes commonly used in cytochemistry that have affinity to nucleic acids, predominantly to RNA. In live cells these dyes accumulate in mitochondria and sensitize the cells to light. The photosensitizing effects of PY and TB were compared with those of another mitochondrial cationic dye, rhodamine 123, and a noncationic dye, merocyanine 540, which binds to the cell membrane. Ninety % reduction of clonogenicity of human epidermoid carcinoma (A-253) cells pretreated with 3.3 microM PY, 0.67 microM TB, 13 microM rhodamine 123, or 18 microM merocyanine 540 was achieved by cell exposure to 0.7, 1.0, 1.2, or 1.5 J/cm2 doses of white light, respectively. The above concentrations of PY, TB, or merocyanine 540 represent the maximal ones at which the effect of each of these dyes alone, in the dark, in reducing cell clonogenicity was less than 12%. Exposure of A-253 cells to light at doses reducing clonogenicity by 50% caused a transient (24 h) arrest of the surviving cell population in the G1 phase of the cell cycle. In contrast to A-253 cells, Chinese hamster ovary cells were highly resistant to the photosensitizing effects of each of the four dyes. Also, the normal human lung fibroblasts (WI-38) were highly resistant to photosensitization by PY, whereas the simian virus 40-transformed WI-38 cells and another carcinoma line (OV-3) were sensitive. The data suggest that PY and TB, like other mitochondrial dyes, may have a selective antitumor photosensitizing activity. PMID- 3342409 TI - Cellular pharmacology of liposomal cis-bis-neodecanoato-trans-R,R-1,2 diaminocyclohexaneplatinum (II) in mouse resident peritoneal macrophages, Kupffer cells, and hepatocytes. AB - The in vitro and in vivo interaction of liposomal cis-bis-neodecanoato-trans-R,R 1,2-diaminocyclohexaneplatinum++ + (II) (L-NDDP) with mouse resident peritoneal macrophages (RPM), Kupffer cells (KC), and hepatocytes was studied. The peak in vitro uptake of L-NDDP by RPM was 12.5 ng elemental platinum/100 micrograms cell protein and constituted 0.2% of the platinum available for phagocytosis. The subsequent release of platinum by RPM was rapid initially, with a 20-fold increase over the first 4 h, followed by a plateau; ultrafilterable (free) platinum constituted 50% of the total platinum released at 24 h. The retained intracellular platinum in RPM at 24 h was close to 50% of that initially present. The peak in vitro uptake of L-NDDP by KC was 11.3 ng platinum/100 micrograms cell protein and amounted to 0.2% of the platinum available for phagocytosis. The release of platinum by KC was detectable only after 4 h of incubation and increased 3-fold over the next 14 h. The ultrafilterable platinum released by KC at 18 h was 40% of the total platinum released. The retained intracellular platinum in KC at 18 h was 33% of that initially present. The peak in vitro uptake of L-NDDP by hepatocytes was almost 50 ng platinum/100 micrograms cell protein and constituted 0.8% of the platinum available for intake. Following the i.v. injection of L-NDDP, hepatocytes contained up to 6-fold higher platinum concentrations than KC. This observation was supported by transmission electron microscopy showing a higher concentration of multilamellar vesicles within hepatocytes than in KC, 5 min after i.v. injection of L-NDDP. These findings suggest that L-NDDP becomes available to the liver following i.v. injection, that both macrophages and hepatocytes play a role in the metabolism of L-NDDP, and that Kupffer cells could mediate a sustained release of platinum in the liver following the interaction with L-NDDP, indicating the potential of L-NDDP for the treatment of tumors in the liver. PMID- 3342410 TI - Geographical pathology of duck livers infected with duck hepatitis B virus from Chiba and Shimane in Japan and Shanghai in China. AB - In order to evaluate geographical differences in the liver pathology of ducks infected with duck hepatitis B virus (DHBV), ducks in Chiba and Shimane, Japan, and Shanghai, China, were investigated. The numbers (DHBV positive/negative) and the maximum age of the ducks examined were 18/10 at 19 mo, 15/1 at 3 yr 4 mo, and 72/27 at 18 mo, respectively. DHBV infection was induced experimentally in ducks from Chiba and Shimane but was present congenitally in those from Shanghai. Ducks were examined regarding liver function tests, conventional histology, immunohistology, electron microscopy, and molecular hybridization for DHBV DNA in the serum and liver. There was no significant difference between DHBV-positive and -negative ducks in bilirubin and transaminase and alkaline phosphatase activities in the sera. Histologically, while the livers of ducks from Chiba and Shimane did not show necroinflammatory (hepatitis) activity, those from Shanghai frequently did (52.5%). Necroinflammatory activity of the Shanghai ducks was present almost equally in both DHBV-positive and -negative livers. The livers of Shanghai ducks but not the other two areas often (8.3%) had ground-glass inclusions which corresponded ultrastructurally to numerous virus particles in the dilated cisternae of the proliferated endoplasmic reticulum. No advanced liver disease, such as cirrhosis or hepatocellular carcinoma, was observed. There was no significant difference in the amount of DHBV DNA in the sera or in its pattern in the liver tissue among ducks of the three areas. In addition, the livers of Chiba ducks frequently had amyloidosis, while those of Shanghai ducks were contaminated with parasites. In conclusion, DHBV infection did not appear to provoke significant hepatitis activity or advanced liver disease in the examined ducks of all three areas, and the DHBV-positive livers from Shanghai ducks showed a different morphological appearance from those of the other two areas. This variation might reflect the difference in the strain of ducks, subtypes of DHBV, environmental factors, or a combination of these influences. PMID- 3342411 TI - A case-control study of male breast cancer. AB - A case-control study was conducted in Los Angeles County, CA, of 75 male breast cancer cases aged 20-74 yr at diagnosis to investigate the role of a number of suspected risk factors. The study involved both interviews and laboratory measurements. Factors under study included fertility and marital history, obesity, alcohol and cigarette consumption, use of drugs known or suspected of causing gynecomastia, family history of breast cancer, history of radiation exposure to the upper body, sex chromatin analysis, serum levels of prolactin, testosterone, estrone, estradiol and sex-hormone-binding globulin, as well as urinary levels of estrone, estradiol, and estriol. Two patients versus no controls tested positive for sex chromatin and were excluded from further analyses. The only statistically significant risk factor identified was greater weight of the cases at age 30; a man who weighed 80 or more kg at age 30 had twice the risk of breast cancer of a man weighing less than 60 kg at that age. Serum estrone levels were positively, and sex-hormone-binding globulin levels were negatively, related to body weight, and we interpret the greater weight of the cases as suggesting that the underlying risk factor is an increased exposure to bioavailable estrogen. None of the differences observed between cases and controls for either the serum or urinary hormone levels was, however, statistically significant and there did not appear to be any large absolute excess of estrogens or deficit of testosterone in the cases. This apparent contradiction may be explained by the fact that there was little difference in weight between the cases and controls at the time of sampling. PMID- 3342412 TI - Effect of tetrahydrouridine on the clinical pharmacology of 1-beta-D arabinofuranosylcytosine when both drugs are coinfused over three hours. AB - When 1-beta-D-arabinofuranosylcytosine (ara-C), 25 mg/m2, is infused over 3 h together with tetrahydrouridine (THU) at 10 to 350 mg/m2 to heavily pretreated patients with solid tumors, Michaelis-Menten type kinetic values are observed with leveling off of delta area under the curve, delta ara-C levels at 3 h, and delta total body clearance after 150 mg/m2 of THU. When the ara-C dose was increased to 50, 75, and 100 mg/m2 coinfusion of 250 or 350 mg/m2 of THU significantly increased plasma ara-C at peak and area under the curve. In contrast, total body clearance and volume of distribution decreased significantly. At 100 mg/m2 of ara-C coinfused with high doses of THU, i.e., at 350 mg/m2, the pharmacokinetics of plasma ara-C was changed from a biphasic decay of plasma ara-C at peaks (control) to a curve similar or identical to a monophasic curve, indicating that THU not only inhibits deamination but also changes the distribution of ara-C. This combination provides plasma ara-C levels (greater than or equal to 10 microM) comparable to high dose ara-C at 1 g/m2. Such plasma ara-C levels are considered to be sufficient for saturation of the kinases catalyzing the production of 1-beta-D-arabinofuranosylcytosine 5' triphosphate. This reduced ara-C dose necessary to achieve saturation of kinases also reduces plasma 1-beta-D-arabinofuranosyluracil levels substantially. Toxicity of this combination was predominantly confined to bone marrow and gastrointestinal toxicity. PMID- 3342413 TI - Noncorrelation of the expression of the c-myc oncogene in colorectal carcinoma with recurrence of disease or patient survival. AB - Our previous work has shown that 26 of 38 cases (68.4%) of primary adenocarcinoma of the colon exhibited significantly elevated levels of c-myc RNA compared to normal colonic mucosa (M. D. Erisman, P. G. Rothberg, R. E. Diehl, C. C. Morse, J. M. Spandorfer, and S. M. Astrin. Mol. Cell. Biol., 5: 1969-1976, 1985; P. G. Rothberg, J. M. Spandorfer, M. D. Erisman, R. N. Staroscik, H. F. Sears, R. O. Petersen, and S. M. Astrin. Br. J. Cancer, 52: 629-632, 1985). In this study, we have compared those levels of expression to the clinical profiles of the affected individuals in an effort to define useful correlates, especially with regard to recurrence of disease and patient survival. Log-rank comparisons of recurrence curves for the entire patient population, for those patients with low levels of c myc RNA in resected tumor tissue, and for those patients with significantly elevated levels of RNA show no statistically significant differences. Similarly, no statistically significant difference was observed between the high- and low myc RNA groups with respect to their survival during the postoperative period of observation (median, 25 months). Consequently, the levels of c-myc gene expression observed in primary tumor tissue did not help to define those individuals at higher or lower risk for recurrence of disease and did not point to the likelihood of increased or decreased survival in individuals undergoing surgery for adenocarcinoma of the colon. PMID- 3342415 TI - Re: Altered leucine metabolism in noncachectic sarcoma patients. PMID- 3342416 TI - Strategies for the integration of Intron A (interferon alfa-2b) into the treatment of hematological malignancies. Proceedings of a satellite symposium at the Third International Conference on Malignant Lymphoma. Lugano June 1987. PMID- 3342414 TI - Urinary human chorionic gonadotropin free beta-subunit and beta-core fragment: a new marker of gynecological cancers. AB - Many investigators have shown that a small proportion (13-36%) of subjects with nontrophoblastic gynecological cancers have elevated serum levels of human chorionic gonadotropin (hCG). The low proportion with detectable levels and the accompanying low titers have limited the use of hCG as a tumor marker. hCG is a glycoprotein composed of two noncovalently linked subunits (alpha and beta), which are the products of separate genes. With the intent of expanding the use of hCG as a tumor marker we investigated levels of hCG free beta-subunit and asialo free beta-subunit and its core glycopeptide (composed of beta-subunit residues 6 40 disulfide-linked to 55-92), collectively called urinary gonadotropin fragments (UGF), in healthy and cancer patients. An immunoradiometric assay was developed, using the core glycopeptide-directed antibody B204, that similarly measures the hCG free beta-subunit and the asialo free beta-subunit and its core glycopeptide. Parallel urine and serum samples were collected from 87 women with active gynecological cancer and hCG and UGF were measured. Just 18% of the women tested had detectable serum levels of hCG (greater than 0.2 ng/ml); none had elevated serum levels in the UGF assay (greater than 0.2 ng/ml). Of the same group, 32% had detectable urine hCG levels (mean titer, 0.50 ng/ml) and 74% exhibited elevated urinary levels in the UGF assay (mean titer, 2.0 ng/ml). In a control group (urines from 50 nonpregnant healthy women), 47 negative and three borderline positive results (0.30, 0.35, and 0.48 ng/ml) were observed in the UGF assay. These results suggested a sensitivity of 74% and specificity of 92% for the UGF test for gynecological cancers. By disease, 70% of those with cervical, 73% of those with ovarian, and 77% of those with endometrial cancers had detectable UGF levels (greater than 0.2 ng/ml). By stage, 50, 62, 75, 86, and 100% of those with stage 1, 2, 3, 4, or recurrent disease, respectively, had positive results. UGF is a promising new marker of gynecological malignancies. PMID- 3342417 TI - Guidelines for the use of Intron A (interferon alfa-2b) in clinical oncology: lessons from the laboratory. PMID- 3342418 TI - Long-term treatment of hairy cell leukemia with interferon alfa-2b. PMID- 3342419 TI - Quantitative electrocardiographic and vectorcardiographic study on newly diagnosed non-insulin-dependent diabetic and non-diabetic control subjects. AB - Quantitative electrocardiographic (ECG) and vectorcardiographic (VCG) analysis was carried out in 113 newly diagnosed, middle-aged, non-insulin-dependent diabetics (61 men, 52 women) and 125 non-diabetic control subjects (56 men, 69 women) in order to explore changes attributable to non-coronary heart disease (diabetic cardiomyopathy) in diabetics. Diabetic men had a prolonged PQ interval and women a more negative P-terminal force and a more leftward frontal QRS axis than their non-diabetic counterparts, but no other significant differences we found between diabetic and non-diabetic subjects in various quantitative ECG and VCG variables when the effect of confounding factors (age, obesity, coronary heart disease, hypertension, drugs) was taken into account. The more negative P terminal force and left axis deviation in diabetic women could be explained by a concomitant left ventricular hypertrophy among them. Non-insulin-dependent (type 2) diabetes, which is commonly preceded by a long duration of asymptomatic hyperglycaemia, is not associated, early in its clinical course, with major ECG and VCG abnormalities suggestive of diabetic cardiomyopathy. PMID- 3342420 TI - Chest pain and behavior in suspected coronary artery disease. AB - This study assessed behavioral activity, dietary and emotional variables among patient cohorts with angina pectoris, atypical chest pain, and no chest pain in whom coronary disease is suspected. Questionnaire responses of 3,899 employed male patients at the time of coronary arteriography were analyzed. Patients with angina pectoris had high levels of coronary-prone and neurotic attitudes, and fatigue variables including feeling unrested on awakening, easy fatiguability, reducing activity at work and arriving home tired. Atypical chest pain patients showed coronary-prone and neurotic attitudes similar to the angina pectoris group but had less coronary occlusion and lower levels of fatigue variables. Compared to the other groups, atypical chest pain patients were more likely to skip breakfast and showed a trend to eat fast. These findings suggest that including assessment of activity levels, fatiguability, eating behavior, neurotic traits and coronary-prone attitudes at time of coronary arteriography can have some limited value for patients with chest pain who may seek cardiac treatment but could benefit from alternative approaches. PMID- 3342422 TI - Impaired left ventricular function during exercise in coronary artery disease and exertional hypotension. AB - To characterize the hemodynamic abnormalities responsible for exertional hypotension coronary artery disease, we studied 11 patients with exertional hypotension during supine cycle ergometer exercise, defined as greater than 10 mm Hg decrease in systolic blood pressure during exercise, and 11 patients without exertional hypotension (controls). Patients were similar with respect to age, left ventricular ejection fraction at rest, and the intensity of exercise relative to maximal treadmill exercise capacity. Peak exercise ejection fraction, determined by radionuclide ventriculography, was significantly lower in patients with, than in those without exertional hypotension (50 +/- 3 vs. 56 +/- 3%; p less than 0.025). Ejection fraction and stroke volume decreased with exercise in patients with exertional hypotension but not in the controls even though changes in end-diastolic volume and mean blood pressure were similar in both groups. Peak exercise systolic blood pressure and rate pressure product were significantly lower in the patients with exertional hypotension than those without. The exercise-induced regional left ventricular contraction abnormalities were more prominent, extensive and frequent in patients with exertional hypotension than controls. Impairment of left ventricular contractile function was further evident by an abnormal end-systolic volume-systolic blood pressure relation in patients with exertional hypotension. These patients attained a much smaller increase in systolic blood pressure compared with controls despite no statistically significant differences in end-systolic volume response to exercise. These findings suggest that exertional hypotension in patients with ischemic heart disease is associated with exercise-induced left ventricular systolic dysfunction secondary to extensive myocardial ischemia. PMID- 3342421 TI - Influence of chronic diuretic therapy on serum, lymphocyte and erythrocyte potassium, magnesium and calcium concentrations. AB - Serum, lymphocyte and erythrocyte potassium, magnesium and calcium concentrations were measured in 31 patients with congestive cardiac failure and 14 patients with mild noncomplicated hypertension, who had been receiving either furosemide or chlorothiazide (with or without potassium supplementation) or a combination of hydrochlorothiazide and amiloride for more than 6 months. Lymphocyte potassium concentrations (pmol/100 cells +/- SE) were as follows: controls 18.1 +/- 1.5, furosemide 14.1 +/- 0.9 (p less than 0.001), furosemide + potassium 12.3 +/- 0.7 (p less than 0.001), chlorothiazide 13.1 +/- 1.0 (p less than 0.001) and hydrochlorothiazide + amiloride 18.6 +/- 0.7 (p = NS). There was a statistically significant relationship between the number of months the patients had been on diuretics and their lymphocyte potassium concentrations. Serum electrolytes, apart from the group receiving chlorothiazide who showed a significant fall in serum K, were unchanged. PMID- 3342423 TI - Relationships between anaerobic threshold and exercise hemodynamic pattern in patients with previous myocardial infarction. AB - In 78 male class I and II NYHA patients with previous myocardial infarction, the relationships between ventilatory anaerobic threshold levels and hemodynamic patterns during a maximal symptom-limited stress test in the supine position were studied. Among the 36 patients with abnormal exercise wedge values, 11 showed an anaerobic threshold (AT) less than 35% of the maximal predicted VO2(mpVO2) (group A) and 23 showed an AT of 36-50% mpVO2 (group B). In 2 patients, the AT was greater than 50% mpVO2. Among the 42 patients with normal exercise wedge pressure, 13 showed an AT of 36-50% mpVO2 (group C), whereas in 29 patients, the AT was greater than 50% mpVO2 (group D). The mean value of AT in group A was significantly lower than in group B (8.6 +/- 0.7 vs. 11.7 +/- 0.5 ml/kg.min; p less than 0.05). No difference was found in the mean of the AT between groups B and C, while the mean value of AT in group D was significantly higher than in group C (16.9 +/- 0.4 vs. 12.9 +/- 0.6 ml/kg.min; p less than 0.005). No significant differences between groups C and D were found in the invasive and noninvasive parameters considered. Groups C and D were statistically different from groups A and B for pulmonary capillary pressures, total pulmonary resistances, stroke indexes, heart rates, arteriovenous O2 differences, total systemic resistances and lactate concentrations. Total pulmonary resistances and heart rates were statistically higher and stroke indexes were statistically lower in group A than in group B. IN CONCLUSION: (1) patients with normal exercise wedge values show a higher AT than patients with abnormal exercise wedge values. (2) Patients with normal exercise hemodynamic patterns classified according to their AT show no difference in hemodynamics; in these patients the level of AT seems to be related to peripheral determinants. (3) Patients with abnormal exercise hemodynamic patterns classified according to their AT level show different hemodynamics and different responses in ventricular function; in these patients the level of AT seems to be related to the cardiac impairment. PMID- 3342424 TI - Patient characteristics and their influence on therapy and its outcome in hypertension of the elderly. AB - A retrospective study was undertaken to analyze the effects of various patient factors on therapy and its outcome in elderly hypertensive subjects. Two hundred and three male hypertensives with a mean age of 63.1 years at entry, were followed in a special hypertension clinic by nurse practitioners under physician supervision, for 2 years or more (mean 3.7 years). Good patient compliance (84%) and blood pressure (BP) reduction were achieved and these were enhanced by advancing age. Neither excessive weight, nor widespread atherosclerosis seemed to interfere with BP control. However, while diastolic BP was well controlled with antihypertensive therapy, systolic BP tended to remain higher than 160 mm Hg in many of the older and more atherosclerotic subjects. Pharmacological treatment did not prevent a gradual although modest deterioration of renal function, which was related to both age and hypertension, and represents a greater problem in black patients. Because of the limitations of such a retrospective study, its conclusions may not be extrapolated for treatment of hypertension in all the elderly. PMID- 3342425 TI - Emergence of cardiovascular diseases in developing countries. AB - Developing countries are subject to the same risks that have contributed to the high incidence of cardiovascular diseases in the already developed countries. Improvements in life expectancy at birth lead to predictable shifts in the cause of-death structure over time. The stage at which cardiovascular diseases may be considered to be 'actively emerging' corresponds to a life expectancy level between 50 and 60 years and, at this level, cardiovascular disease mortality accounts for 15-25% of all deaths. The average life expectancy at birth in developing countries for the year 2000 is projected to be 60 years or more and it may be expected that by that time cardiovascular diseases would be actively emerging or established in virtually every country. In many developing countries today, life-style pattern that is associated with high rates of coronary heart disease is not yet widespread and it is therefore logical that a strategy of prevention should include efforts to inhibit the entrenchment and spread of unhealthy life-styles in the community (i.e., primordial prevention). At the country level, cardiovascular disease prevention and control cannot be considered in isolation and must be related to prevailing national health priorities and competing claims from other sectors of development. In poorer countries where life expectancy is below 50 years primordial prevention activities are likely to be restricted--perhaps to smoking and hypertension control. In middle-income countries a broader based approach to primordial prevention is feasible and is more likely to be acceptable. PMID- 3342426 TI - Secular changes in mortality among survivors of unstable angina and myocardial infarction. AB - Seven hundred and ninety-four males under 60 years who survived a first episode of unstable angina or myocardial infarction by 28 days were admitted to St. Vincent's Hospital between 1965 and 1981 inclusive. They were followed for at least 4 years: 1-, 2- and 4-year mortality during the follow-up period did not alter significantly during the 17 years. Significant changes did take place over time in the severity of the coronary attacks and in the risk profile of the patients. A greater number of complicated infarcts occurred in the later years and there were fewer smokers and more hypertensives. There was a significant increase over time in the number of initial cigarette smokers who stopped after the coronary attack. Changing methodology made secular changes in cholesterol levels difficult to interpret. PMID- 3342428 TI - Writing a research proposal: the first step in conducting research. Part 1. PMID- 3342427 TI - Ischaemic heart disease in urbanized Papua New Guinea. An autopsy study. AB - Ischaemic heart disease was unknown in Papua New Guinea until 1964 when the first case was reported. Since then there has been a rapid rise in frequency confined to its major urban area, the capital, Port Moresby. The findings are based on post-mortems in Port Moresby and in Goroka, one of the major towns in the Highlands with its more traditional population, where ischaemic heart disease is now beginning to be seen. PMID- 3342430 TI - Unique features of secretory granules observed in the pituitary growth hormone secreting (GH) cells of the musk shrew (Suncus murinus L). AB - Unique rod-shaped secretory granules were observed among oval or spherical secretory granules in GH cells of the anterior pituitary gland of musk shrew using the protein A-gold procedure combined with electron microscopy. The rod shaped and spherical secretory granules were both immunoreactive by the immuno gold method using antiserum to sheep GH. The rod-shaped secretory granules, which seem to be formed directly from the Golgi vesicles, extend from several hundred to several thousand nm in length. They often touch each other and fuse. The spherical secretory granules are also unique in that they may also fuse with loss of dense contents to leave "empty" circular membrane profiles in the cytoplasm. Both the rod-shaped and spherical secretory granules are secreted from the cell by exocytosis. PMID- 3342429 TI - In vivo autoradiographic analysis of prolactin binding in brain and choroid plexus of the domestic ring dove. AB - The binding of intravenously administered prolactin to choroid plexus and brain tissue was determined radioautographically in the ring dove, a species that exhibits prolactin-induced alterations in brain function. An intense autoradiographic reaction was detected over the epithelial cells of the choroid plexus 5 min after the intravenous injection of 125I-ovine prolactin. A significant reaction was also observed over the infundibulum but no significant uptake of prolactin occurred in other brain areas. The binding of radiolabelled prolactin to infundibulum appeared to be non-specific, since excess unlabelled hormone did not reduce silver grain density. In contrast, 125I-ovine prolactin binding in choroid plexus was significantly reduced by excess unlabelled ovine prolactin or human growth hormone, but not by ovine luteinizing hormone. Specific binding to choroid plexus was also detected in vitro. The lack of significant brain uptake of prolactin in vivo is discussed in relation to recent in vitro evidence for specific binding sites for prolactin in several dove brain regions. Similarities between the binding results obtained in this avian species and those reported previously in mammals suggest that the two vertebrate groups exhibit similar patterns of prolactin interaction with neural target tissues. PMID- 3342431 TI - The lattice arrangement of the collagen fibres in the submucosa of the rat small intestine: scanning electron microscopy. AB - The three-dimensional architecture of the submucosal collagen fibres of the rat (3 weeks old) small intestine was examined by scanning electron microscopy using a selective microdissection method. The main framework of the submucosa was composed of two arrays of collagen fibre bundles running diagonally around the intestinal wall, one set in a clockwise direction, the other counterclockwise. These fibre bundles were about 5 micron diameter and were oriented at a range of angle +/- 30 degrees -50 degrees to the longitudinal axis of the intestine. With the advantage of the SEM observation it was demonstrated that these fibres in different arrays did not constitute two separate layers but interwove to form a unified lattice sheet. An irregular network of fine collagen fibrils over the main framework was also seen. The significance of their arrangement is discussed with respect to the skeletal function of the submucosa in the intestine. PMID- 3342432 TI - Adhesion, proliferation, and adipogenesis in primary rat cell cultures: effects of collagenous substrata, fibronectin, and serum. AB - The effects of collagenous substrata, fibronectin, and fetal bovine serum on the adhesion, proliferation, and adipogenesis of rat stromal-vascular cells are reported. There was no effect on initial stromal-vascular cell-attachment by fetal bovine serum or fibronectin. The number of cells attached to a hydrated collagen-gel was almost twice (P less than 0.04) the number attached to dried collagen-gel or dried denatured collagen-gel. Total number of cells after 5 days in culture was similar among the collagenous substrata and among the treatments with or without fibronectin in the growth media. Total number of cells increased significantly (P less than 0.02) with 10% FBS. Adipocytic formation was inhibited by hydrated collagen-gel (P less than 0.02) compared to dried collagen-gel or dried, denatured collagenous substrata. An interaction occurred between dried, denatured gel and fetal bovine serum so that total formation of adipocytes increased by increasing the level of fetal bovine serum (P less than 0.07). Adipocytic formation was inhibited by hydrated collagen-gel at all levels of fetal bovine serum. The percentage of cells that converted to adipocytes was significantly lower (P less than 0.01) on hydrated collagen-gel compared to dried, denatured or dried collagen-gel. Percentage of conversion was not significantly different among levels of fetal bovine serum, although this percentage increased as fetal bovine serum level increased. Adipocytic conversion was not different between fibronectin-treated or untreated cells. Morphology of stromal vascular cells was similar on dried collagen and dried, denatured collagen-gel, but tended to remain bipolar on hydrated collagen-gel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342433 TI - Freeze-fracture analysis of structural reorganization during meiotic maturation in oocytes of Xenopus laevis. AB - During meiotic maturation, the cortex of oocytes of Xenopus laevis undergoes structural reorganization, visualized in this study by freeze-fracture electron microscopy. In the full-grown but immature oocyte, annulate lamellae are dispersed throughout the subcortex of the egg, 5 to 20 micron from the plasma membrane. The annulate lamellae consist of well-organized stacks of membrane with visible pores. Stimulation of meiotic maturation by progesterone leads to disruption of the annulate lamellae and formation of an elaborate cortical endoplasmic reticulum which surrounds the cortical granules and intertwines throughout the cortex of the mature egg. Pore-like structures similar to those previously observed in the subcortical annulate lamellae are observed in the mature cortical endoplasmic reticulum. The cortical endoplasmic reticulum is often in close apposition with the plasma membrane and with membranes of cortical granules, but no junctions are visualized. This study provides further evidence that the cortical endoplasmic reticulum develops during progesterone-stimulated meiotic maturation in vitro, and that the annulate lamellae are precursors to the cortical endoplasmic reticulum. PMID- 3342435 TI - Binding of intravenously injected antibodies against laminin to developing and mature endocrine glands. AB - To determine whether circulating antibodies against laminin can bind in vivo to basement membranes within endocrine glands, affinity-purified sheep or rabbit anti-laminin IgG was intravenously injected into rats. One to five hours after injection, anti-laminin IgG was bound to all basement membranes of adrenal and anterior pituitary glands of mature as well as 2-day-old newborn rats as shown by immunofluorescence microscopy. After the injection of anti-laminin conjugated directly to horseradish peroxidase (HRP), HRP reaction product was also present throughout adrenal and pituitary basement membranes in mature and immature glands 1-5 h post-injection. Ultrathin Lowicryl sections from rats that received unconjugated rabbit anti-laminin IgG 1 h prior to fixation with paraformaldehyde were labeled directly with anti-rabbit IgG-colloidal gold. In these cases, gold also bound specifically over the lamina densa and lamina rara. When adrenal or pituitary glands from mature rats were examined by immunofluorescence 1 week after the injection of sheep anti-laminin IgG, the patterns and amounts of bound sheep IgG were indistinguishable from those observed 1 h after injection. In contrast, significantly less fluorescence was present in glands from 7-day-old rat pups that had received anti-laminin IgG 5 days earlier. In addition, when anti-laminin IgG-HRP was injected into newborns and glands were fixed 5 days later, lengths of labeled endothelial and epithelial basement membranes were often interspersed with unlabeled lengths in zones of cellular proliferation in the outer adrenal cortex and throughout the pituitary gland. These results indicated that unlabeled basement membranes in these regions were probably assembled after the injection of anti-laminin IgG, which would also explain diminished labeling of basement membranes in these animals. Despite the continued presence of heterologous anti-laminin IgG within endocrine basement membranes, however, rat IgG, rat C3, inflammatory cells, or histologic abnormalities were observed in neither newborn nor adult glands under the conditions examined here. Sections from rats injected with control IgG or control IgG-HRP were entirely negative by immunofluorescence, immunoperoxidase, and immunogold techniques. We therefore conclude that (1) apparently large amounts of circulating anti-laminin IgG can bind to adrenal and pituitary basement membranes, and (2) at least some of these basement membranes are assembled during development by progressive splicing of newly synthesized matrix into that already present. PMID- 3342434 TI - Peptidergic neurohormonal systems in the basal hypothalamus of the ferret and the mink: immunocytochemical study of variations during the annual reproductive cycle. AB - The hypothalamic systems secreting corticotropin-releasing hormone (CRF), somatostatin, oxytocin, vasopressin and luteinizing hormone-releasing hormone (LHRH) were characterized using immunochemistry, and variations were studied in relation to the recrudescence of testicular activity in the ferret and the mink, two species with opposite photoregulation of their annual reproductive cycles. Under the present conditions of study, the immunoreactivity of the CRF, somatostatin, and oxytocin systems showed no significant variation in either species. In contrast, in these two species, the immunoreactivity of the LHRH system varied considerably depending on the date of observation. The increase in the number and immunoreactivity of the LHRH-secreting neurons that occurred in November in the mink and in January in the ferret, is in agreement with previous results showing that the photoperiod plays an essential role in regulating the annual activity of the testis and that the photoperiodic environmental conditions required for the activation of the LHRH system differ between the species. Similarly, correlations could be found between an increase in immunoreactivity of the vasopressinergic axons projecting to the external median eminence and the recrudescence of testicular activity. PMID- 3342436 TI - Photoperiod-dependent changes in TSH-like immunoreactivity of cells in the hypophysial pars tuberalis of the Djungarian hamster, Phodopus sungorus. AB - Certain secretory cells in the hypophysial pars tuberalis of the Djungarian hamster display marked circannual structural alterations. The present investigation deals with the immunohistochemical properties of this cell group. A distinct TSH-like immunoreactivity was found in secretory cells of this type in the pars tuberalis of animals exposed to long photoperiods, whereas under short photoperiods the TSH-like immunoreactivity was nearly absent. In the pars distalis, the number and distribution of TSH-positive cells did not differ significantly between animals maintained under long and under short photoperiods. LH- and FSH-positive cells could not be detected in the pars tuberalis, but they are clearly present in the pars distalis of both groups of hamsters. Our immunocytochemical results suggest that photoperiodic stimuli influence the secretory activity of TSH-like immunoreactive cells in the pars tuberalis. A connection with the neuroendrocrine-thyroid axis is discussed. PMID- 3342437 TI - Lymphocytes of the intestinal mucosa of chickens. AB - Examination, by light and electron microscopy, of the morphology and the staining properties of intraepithelial lymphocytes from the intestine of the chicken revealed a population of lymphoid cells, of which a proportion (up to 20%) is granulated. The majority of cells were immunoreactive with anti-T cell serum and can therefore be considered to be related to T-lymphocytes, but they did not proliferate when cultured with phytohaemagglutinin. The granulated cells were identical to those previously designated globule-containing leukocytes, but were distinct from mast cells in their morphology, staining reactions and the stability of the granules in different fixatives and buffers. PMID- 3342438 TI - Chromosomes and their relationship to nuclear components during the cell cycle in Chinese hamster cells. AB - Chromosomes and their relationship to nuclear components during various phases of the cell cycle were studied with different fixation, embedding, and enzyme techniques. The results showed that interphase chromosomes may have oriented in such a way that a given locus became associated with the nuclear membrane. Some chromosomes also appeared to interact with the nucleolus. The nuclear matrix materials, however, were distributed between the chromosomes and formed a delineating boundary for the chromosomes. These matrix materials, furthermore, formed channel-like structures within the nucleus and towards the cytoplasm through their interaction with nuclear pore complexes. During mitosis, chromosomes were encapsulated with material that appeared to be derived from the matrix, disintegrated residues and fragments of the nuclear envelope, the lamina, and nucleolar material. These chromosome-associated materials seen in mitosis appeared to serve as foci for formation of new nuclear components in subsequent interphase. PMID- 3342439 TI - Structural changes produced in Kupffer cells in the rat liver by injection of lipopolysaccharide. AB - The fine structure of Kupffer cells has been studied at various times after an intravenous injection of lipopolysaccharide of Salmonella abortus equii. The most prominent effects were: an increase in the number and dimensions of phagocytic vacuoles (often containing ingested LPS and neutrophilic granulocytes); mitochondrial damage, including disintegration of the matrix and cristae; an increase in the amount of dilated, lucent rough endoplasmic reticulum; presence of fat droplets in the cytoplasm. Five days after injection of lipopolysaccharide, the Kupffer cells had resumed their normal ultrastructure. Several minutes after injection of lipopolysaccharide, platelets adhered to the Kupffer and endothelial cells. Between one and six hours, neutrophilic granulocytes accumulated in the liver sinusoids. The resulting obstruction of the hepatic microcirculation most probably affected cellular ultrastructure by ischaemia. At three days, the number of Kupffer cells was doubled, and increased further at later time intervals. PMID- 3342440 TI - Development and retention of phenotypically specialized cells in pituitary allografts in the hamster (Mesocricetus auratus). AB - We used immunohistochemistry to identify cells present in pituitary allografts in the hamster. Hypophyses removed from neonatal hamsters or adenohypophyses removed from adult females were placed beneath renal capsules of hypophysectomized adult females. Serum PRL, LH, and GH concentrations were measured at two, five and eight weeks after placement of allografts. Allografts were removed after eight weeks and stained for cells containing PRL, LH, FSH, GH, or ACTH. Allografts did not release LH or GH. Those of adult adenohypophyseal tissue released significantly more PRL. The morphology of allografts of neonatal hypophyseal tissue resembled that of the adult adenohypophysis in situ. Lactotrophs, corticotrophs, somatotrophs and LH-cells were observed; very few FSH-cells were present. Allografts of adult adenohypophyseal tissue contained pituitary cells, numerous cavities, often enclosing lymphoid cells, and fibrous tissue. Atypical lactotrophs were the numerically dominant cells in these allografts; all other cells were present. The LH-cells outnumbered FSH-cells. These observations suggest that: (a) development of normal adenohypophyseal morphology can occur in an ectopic position; (b) intracellular hormones are present in cells in an ectopic site; (c) development and retention of intracellular FSH is more dependent on occupation of the normal position of the adenohypophysis than is retention of intracellular LH; and (d) release of PRL occurs from atypical cells in allografts of adult adenohypophyseal tissue. PMID- 3342441 TI - Mammalian-like differentiation of gastric cells in the shark Hexanchus griseus. AB - Gastric glands of submammalian vertebrates are formed by one single cell type known as the oxyntopeptic cell. This cell secretes both hydrochloric acid and pepsinogen. In mammals, this cell differentiates into an acid secreting cell and a pepsinogen secreting one. In the elasmobranch fish Hexanchus griseus we observed, by means of histological studies at the light- and electron-microscopic levels, two different cell types for the secretion of acid and zymogen. This organization represents an evolutionary divergence in a primitive animal, i.e., the appearance of a feature that is acquired much later in evolution, in mammals. PMID- 3342442 TI - Response of the human testis to long-term estrogen treatment: morphology of Sertoli cells, Leydig cells and spermatogonial stem cells. AB - The present investigation is concerned with the morphological changes observed in human testicular tissue following prolonged estrogen administration. Testicular material obtained from 11 transsexual patients who had been submitted to long term estrogen treatment prior to sex-reversal surgery was studied by means of light- and electron microscopy. The testes of all patients examined present a more or less uniform appearance: There are narrow seminiferous cords surrounded by an extensively thickened lamina propria. They contain Sertoli cells and spermatogonia exclusively. There is no evidence of typical Leydig cells. The persisting spermatogonia show the characteristic features of pale type-A spermatogonia, whereas dark type-A spermatogonia are almost completely eliminated from the epithelium. In view of the fact that spermatogonia that survived radiotherapy and treatment with various noxious agents have recently been regarded as the stem cells of the human testis, it is suggested that also the majority of those spermatogonial types that are less sensitive to disturbances of the endocrine balance may consist of stem cells. The present results, therefore, corroborate the concept that the stem cells of the human testis may be derived from pale type-A spermatogonia or the variants of this cell type. Sertoli cells display two types of ovoid nuclei. In contrast to untreated material the nuclei lie adjacent to the basal lamina, and organelles and telolysosomes are confined to the apical cytoplasm. The apico-basal differentiation of mature cells, therefore, is not observed. Moreover, typical organelles and inclusions of mature cells are absent, as are the junctional specializations. Thus, Sertoli cells have transformed into immature cells, resembling precursors prior to puberty. Fibroblast-like cells in the interstitial tissue, which display strongly lobulated nuclei, a well-developed smooth endoplasmic reticulum, lipid droplets, and numerous inclusions are assumed to represent dedifferentiated Leydig cells. Since after estrogen treatment serum testosterone and gonadotropin levels are known to be reduced, it appears that the morphological changes correlate well with the endocrine status. PMID- 3342443 TI - Abundant GABAergic innervation of rat posterior pituitary revealed by inhibition of GABA-transaminase. AB - An antibody against gamma-aminobutyric acid (GABA) was used to identify GABAergic elements immunocytochemically in the rat posterior pituitary. In order to increase the intracellular concentration of GABA, rats were treated with the GABA transaminase inhibitor gamma-vinyl-GABA (GVG). Light-microscopic observations of Vibratome and semithin sections revealed the presence of numerous immunoreactive nerve fibers throughout the neural lobe; the mean number and length of these fibers increased by 90% after GVG treatment. Electron microscopy demonstrated the immunostained axons to be of small diameter. The reaction product was confined to small vesicles. No immunostaining occurred in pituicytes. The richness of the GABAergic innervation of the neural lobe contrasts with previous reports using antibodies against glutamate decarboxylase and supports the idea that GABA participates in the presynaptic control of neurosecretion. PMID- 3342444 TI - Evidence for neuroendocrine regulation of preadipocyte proliferation and differentiation. AB - Cells in fetal adipose tissue and cells in vitro are characterized by rapid proliferation. Serum factors have been shown to be important for the rapid proliferation of cells in vitro. The present experiment was performed to determine if neuroendocrine regulatory mechanisms of the fetus can influence the actions of serum factors on preadipocyte proliferation and differentiation in vitro. Sera were obtained from decapitated fetal pigs and intact littermates during gestation. Sera were tested for their effects on primary cultures of preadipocytes and stromal-vascular cells derived from inguinal adipose tissue of young Sprague-Dawley rats. Coverslip cultures were used for histochemical analysis of enzymes after 12 days of incubation with test media. Analysis of growth curves produced from sequential [3H]-thymidine labeling indicated that fetal age influences rates of proliferation. Sera from decapitated fetal pigs specifically reduced the number of proliferating preadipocytes in culture. Sera from decapitated fetal pigs induced a minimum of 50% less differentiation of sn glycerol-3-phosphate dehydrogenase activity than sera from intact pigs at all fetal ages. Histochemical staining for enzymes of differentiating preadipocytes was also reduced in cultures incubated with sera from decapitated fetal pigs in comparison to sera from intact pigs. The present study has demonstrated that the in vivo effect of decapitation on fetal adipose tissue development is a consequence of alterations in systemic factors present in serum in response to removal of central regulation by the hypothalamic-pituitary axis. PMID- 3342445 TI - Immunohistological localization of IgG1, IgA and secretory component in the bovine mammary gland during involution. AB - Immunoperoxidase methods were used to localize secretory component, immunoglobulin A and immunoglobulin G1 in mammary tissue from dairy cows. In lactating tissue, immunostaining for immunoglobulin A and secretory component was observed primarily in the luminal contents of alveoli. By day 2 of involution, alveolar epithelial cells stained for both immunoglobulin A and secretory component. Staining of alveolar epithelial cells for immunoglobulin A and secretory component continued throughout the period of mammary involution. No staining for secretory component was observed in the interalveolar stromal area. Immunoglobulin G1 immunostaining was localized primarily in the interalveolar areas in lactating tissue, but was localized at the apical and basolateral surface of alveolar cells on day 2 of involution. In contrast to immunoglobulin A, immunoglobulin G1 staining of epithelial cells did not persist and was primarily in the interalveolar areas by day 4. These results suggest that an increased localization of immunoglobulin G1 in bovine mammary epithelial cells may occur transiently in early involution, while an increase in immunoglobulin A and secretory component localization in epithelial cells persists throughout involution. PMID- 3342446 TI - alpha-Actinins and the DMD protein contain spectrin-like repeats. PMID- 3342447 TI - Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy. AB - We show that Duchenne muscular dystrophy (DMD) selectively affects a subset of skeletal muscle fibers specialized for fast contraction. Muscle fiber types were characterized immunohistochemically with monoclonal antibodies that distinguish isoforms of fetal and adult-fast or adult-slow myosin heavy chain present in the same fiber. Fetal myosin expression increased with patient age and was not due to arrested development but rather to de novo synthesis, which served as a sensitive indicator of muscle regeneration. A subset of fast fibers were the first to degenerate (type IIb). Extensive fast fiber regeneration occurred before slow fibers were affected. These results suggest that the DMD gene product has a specific function in a subpopulation of muscle fibers specialized to respond to the highest frequency of neuronal stimulation with maximal rates of contraction. PMID- 3342448 TI - At least three different RNA polymerase holoenzymes direct transcription of the agarase gene (dagA) of Streptomyces coelicolor A3(2). AB - Using a combination of gel filtration and anion exchange FPLC, three different RNA polymerase holoenzymes from Streptomyces coelicolor A3(2) have been separated. Each holoenzyme transcribes from only one of the four promoters of the S. coelicolor A3(2) dagA gene. Holoenzyme reconstitution experiments identified the sigma factors responsible for recognition of two of the promoters. The previously identified E sigma 49 transcribes from the dagA p3 promoter, whereas a novel species, E sigma 28, recognizes the dagA p2 promoter. Circumstantial evidence suggests that the third holoenzyme, which transcribes from the dagA p4 promoter, is the previously identified E sigma 35. This level of transcriptional complexity supports the idea that RNA polymerase heterogeneity may play a central role in the regulation and coordination of gene expression in this biochemically and morphologically complex bacterium. PMID- 3342449 TI - Distribution of R-cognin and choline acetyltransferase in the ganglion cell layer of developing chick neural retina. AB - Retina cognin, a cell membrane glycoprotein which mediates cell-cell recognition and adhesion in vitro, is initially present throughout the retina and becomes confined to the ganglion cell layer at 14-15 days of embryogenesis. Within this layer it is found on membranes of virtually all ganglion and displaced amacrine cells, but not on membranes of retinal glial cells (Muller fibers) which traverse this layer. The distribution of cognin as determined by immunocytochemistry is described and compared with that of choline acetyltransferase. The significance of cognin as a possible address marker during development of neural retina is discussed. PMID- 3342450 TI - Developmental modifications of sheep kidney antigens. AB - We have used monoclonal antibodies to study the changes in the expression of four kidney antigens during organogenesis in the sheep. Two of these antibodies, EE24.6 and EJ30.1, label intensely only the adult kidney, whereas the other two, EK17.1 and EJ15.1, bind to the extracellular matrix of the embryonic kidney. For EJ15.1, the staining of the extracellular matrix decreases temporarily during the second half of intrauterine life, a period during which a light staining appears in the mesangium. For the other, EK17.1, the extracellular matrix staining in the stroma gradually decreases as the embryo grows, while staining of the mesangium and the arterial intima becomes evident. With EK17.1, fibronectin is identified in the extracellular matrix of the embryonic kidney and intracellularly in the mesangial cells after these cells have colonized the glomerulus. The mesonephros staining seems to be the same as that of the metanephros. In the adult, extraglomerular vascular endothelial cells bind EK17.1, whereas intraglomerular endothelial cells do not express fibronectin, which suggests a functional difference between endothelial cells in these two localizations. PMID- 3342452 TI - Electrophoretic pattern of NADPH-dependent oxidoreductive activities in K 562 and HL 60 leukemic cell lines. AB - Morphological and functional differentiation of hemopoietic cells is accompanied by the expression of lineage-specific protein markers. NADPH-oxidoreductive enzymatic activities in HL 60 and K 562 leukemic cell lines, compared with granulocytes and erythrocytes, show a NADPH-oxidizing and a NADPH-diaphorase activity. The oxidizing activity, absent in erythrocytes, has the same electrophoretic migration in HL 60 cells and granulocytes while it is different in K 562 cells. The diaphorase, absent in HL 60 cells and granulocytes, has the same migration in erythrocytes and K 562 cells, although with a slightly different quantitative expression. K 562 cells induced to differentiation with arabinofuranosylcytosine show the appearance of a band of NADPH-oxidizing activity of granulocytic type, together with the major band found in these cells. PMID- 3342451 TI - Differentiation of intestinal and ectopic endocrine cells from avian gastric and pancreatic endoderm. AB - The chorio-allantoic grafts analysed were prepared from avian proventricular endoderm combined with its own or pancreatic mesenchyme and from re-associated pancreatic layers. Intestine developed ectopically in some grafts: in these, endocrine cells typical of intestine differentiated irrespective of the source of the endoderm or mesenchyme. In addition, endocrine cells inappropriate for the surrounding histology were detected in small numbers in grafts of all categories. Clearly it is not the mesenchyme that is responsible but perhaps some aspect of the procedure, which may relate to stressful stimuli thought to provoke intestinal metaplasia. The differentiation of inappropriate cells aids in understanding the occurrence of ectopic endocrine tumours. PMID- 3342453 TI - Cytochrome P-450-mediated oxidation of substrates by electron-transfer; role of oxygen radicals and of 1- and 2-electron oxidation of paracetamol. AB - The mechanism by which the hepatic cytochrome P-450 (Cyt. P-450) containing mixed function oxidase system oxidizes the analgesic drug paracetamol (PAR) to a hepatotoxic metabolite was studied. Since previous studies excluded the possibility of oxygenation of PAR, three other mechanisms, namely direct 1 electron oxidation by a Cyt. P-450-ferrous-dioxygen complex under concomitant formation of H2O2 to N-acetyl-p-semiquinone imine (NAPSQI), direct 2-electron oxidation by a Cyt. P-450-ferric-oxene complex to N-acetyl-p-benzoquinone imine (NAPQI) and indirect oxidation by active oxygen species released from Cyt. P-450, were considered. Indirect oxidation by active oxygen species was not involved, as active oxygen scavengers such as superoxide dismutase, catalase and DMSO did not affect the oxidation of PAR in hepatic microsomes. No reaction products characteristic for a direct 1-electron oxidation of PAR by Cyt. P-450 were observed: neither NAPSQI radical formation was detectable by ESR, nor PAR-dimer formation, nor stimulation of the microsomal H2O2 production was found to occur. In fact, PAR inhibited the spontaneous microsomal H2O2 formation. Studies on the reactions of NAPSQI with glutathione (GSH) revealed that NAPSQI hardly conjugated with GSH to a 3-glutathionyl-paracetamol conjugate (PAR-GSH) conjugate. The reactions of the elusive reactive metabolite formed during microsomal oxidation of PAR in the presence of GSH closely resembled those of synthetic NAPQI: both PAR-GSH and oxidized glutathione (GSSG) formation occurred. Furthermore, in agreement with a 2-electron oxidation hypothesis, iodosobenzene-dependent oxidation of PAR by cyt. P-450 in the presence of GSH resulted in the formation of the PAR-GSH conjugate. It is concluded that bioactivation of PAR by the Cyt. P 450 containing mixed-function oxidase system consists of a direct 2-electron oxidation to NAPQI. PMID- 3342454 TI - Stereoselective aspects of the metabolic activation of benzo[a]pyrene by human skin in vitro. AB - Benzo[a]pyrene (BP) is activated within tissues in both a regio- and a stereoselective manner and, since human skin is sensitive to tumour induction by polycyclic aromatic hydrocarbons (PAH), the steroselective metabolism of BP in this tissue has been investigated. Samples of skin from eleven individuals were treated with [3H]BP in short-term organ culture. Two samples were also treated with mixtures of [14C](+)- and (-)-trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (BP-7,8-dihydrodiol) in varying proportions. Following application of [3H] BP, more 7,8-dihydrodiol was recovered from the skin itself than from the culture fluid in ten cases; no 7.8-dihydrodiol was detected in extracts from the eleventh. The 7,8-dihydrodiol metabolite was extracted predominantly (range 74 greater than 99%) as the (-)-enantiomer in nine of these ten patients, although proportionately more (+)-enantiomer was recovered from the culture fluid than from the skin in each case. The relative proportions of [3H]BP tetrols derived from syn- and anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydroxybenzo[a]pyrene (BPDE) detected in these extracts was more variable. When skin samples were treated with [14C]BP-7,8-dihydrodiol, more anti- than syn-BPDE-derived tetrols were extracted, irrespective of the optical purity of the dihydrodiol applied. These findings provide evidence for interindividual variations in the stereoselective metabolism of BP, which may be of some importance in determining individual susceptibility to PAH-induced skin carcinogenesis. PMID- 3342456 TI - Small hydrocarbons formed by the peroxidation of squalene. AB - Experiments were undertaken to determine whether peroxidized squalene forms isoprene in a manner such that peroxidation could be considered as a possible route for the formation of in vivo human breath isoprene. Small hydrocarbons derived from peroxidation of positions 1-6 of squalene were identified in the head space. The most unusual product, proposed to arise from peroxidation of carbon 1 and intramolecular cyclization, was a mixture of dimethylcyclopentadiene isomers. Sonication of an aqueous mixture or low O2 partial pressure favored isoprene formation. PMID- 3342455 TI - Interaction of surfactants with vesicle membrane of dipalmitoylphosphatidylcholine: fluorescence depolarization study. AB - The effect of surfactants on the "fluidity" of dipalmitoylphosphatidylcholine (DPPC) vesicle membrane was studied by means of the fluorescence depolarization technique with fatty acid fluorescent probes, in which the anthroyloxy group is introduced at different positions along the acyl chain. Three types of surfactants were examined; anionic sodium alkylsulfates, cationic alkyltrimethylammonium chlorides, and non-ionic alkanoyl-N-methylglucamides (MEGA n). Perturbing effects of the surfactants depended on both the alkyl chain-length and the type of head group. Sodium alkylsulfates with octyl- and decyl-chain and alkyltrimethylammonium chlorides with octyl-, decyl- and dodecyl-chain did not affect the membrane fluidity when incorporated in the membrane, whereas sodium dodecylsulfate and tetradecyltrimethylammonium chloride decreased the membrane fluidity at both gel and liquid crystalline states of the membrane. All the MEGA series surfactants decreased the membrane fluidity, whose perturbing potency was in the order of MEGA-8 less than MEGA-9 approximately equal to MEGA-10. The perturbation at different depths in the membrane by sodium dodecylsulfate and MEGA-9 was also examined. No significant change in the fluidity gradient across the membrane was induced by the addition of these surfactants. PMID- 3342457 TI - Surface topography of sulfatide and gangliosides in unilamellar vesicles of dipalmitoylphosphatidylcholine. AB - The property of the dyes, acridine orange and methylene blue, to exhibit metachromatic changes upon binding to negatively charged groups that are within a defined spatial separation was employed to study the lateral and transverse topography of sulfatide and gangliosides GM1 and GD1a mixed with dipalmitoylphosphatidylcholine (DPPC) in unilamellar vesicles. The spectral changes of the dyes in the presence of liposomes containing anionic glycosphingolipids (GSLs) (hypochromism and frequency shift) are typical of polyanionic lattices while minor changes are found for neutral lipids. The metachromatic changes are abolished by the presence of Ca2+ in the external medium. The proportion of anionic GSLs accessible to the dyes on the external surface of the liposomes is greater as the GSLs are more complex (sulfatide less than GM1 less than GD1a) and as its proportion in the mixture decreases. The number of molecules of anionic GSLs that are laterally distributed on the external surface in a position favorable for the formation of dye dimers (at intermolecular distances not exceeding 1 nm) is greater for sulfatide than for ganglioside. This is correlated to the greater intermolecular distances and delocalization in ganglioside-, compared to sulfatide-containing interfaces. The experimental values indicate that the mixture with DPPC of any of the anionic GSLs studied behaves as if it was more enriched in the GSLs compared to the proportions of the whole mixture. PMID- 3342458 TI - Inhibitors of sterol biosynthesis. Synthesis and activities of ring C oxygenated sterols. AB - The chemical syntheses of a number of C27 ring C oxygenated sterols have been pursued to permit evaluation of their activity in the inhibition of sterol biosynthesis in cultured mammalian cells. Thus, 5 alpha-cholest-7-ene-3 beta, 11 alpha-diol, 3 alpha-hydroxy-5 alpha-cholest-9(11)-en-12-one, and the previously unreported 11 alpha-hydroxy-5 alpha-cholest-7-en-3-one, 5 alpha-cholest-9(11)-ene 3,12-dione, and 3 beta-hydroxy-5 alpha-cholest-9 (11)-en-12-one have been synthesized. The effects of these compounds on the synthesis of digitonin precipitable sterols from labeled acetate in mouse L cells and on the levels of 3 hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in the same cells have been investigated and compared with previously published data on other ring C oxygenated sterols. 5 alpha-Cholest-7-ene-3 beta, 11 alpha-diol was shown to be the most potent inhibitor of sterol synthesis. PMID- 3342459 TI - N-pyrene dodecanoyl sulfatide as membrane probe: a study of glycolipid dynamic behavior in model membranes. AB - An N-linked pyrene-dodecanoyl sulfatide was employed to measure the ratio of excimer fluorescence to monomer fluorescence intensities (E/M). The E/M values provided information about both the dynamic behavior and the structural distribution of the labelled glycolipid in note dispersion of micellar sulfatides and multilamellar vesicles of different phospholipids. Most of the labelled sulfatide seems to be located in domains sequestered from the surrounding phospholipids still above the phase transition temperature of the vesicles. The glycolipids sequestered in these domain environments are less sensitive to the structural changes that the addition of cholesterol or Ca2+ can induce in the phospholipid regions during the phase transition. PMID- 3342460 TI - Comparative brain and plasma pharmacokinetics and anticancer activities of chlorambucil and melphalan in the rat. AB - Equimolar doses of chlorambucil and melphalan (both 10 mg/kg) were administered i.v. to anesthetized rats, and the plasma and brain concentrations of chlorambucil, its metabolites 3,4-dehydrochlorambucil and phenylacetic mustard, and melphalan were determined by high-performance liquid chromatography from 5 to 240 min thereafter. Chlorambucil demonstrated a monophasic disappearance from plasma, with a half-life of 26 min. The compound was 99.6% plasma-protein-bound. Chlorambucil underwent beta-oxidation to yield detectable concentrations of 3,4 dehydrochlorambucil and substantial amounts of phenylacetic mustard in the plasma. Low concentrations of chlorambucil and phenylacetic mustard were detected in the brain. Calculated from the areas under the concentration-time curves, the brain:plasma concentration integral ratios of chlorambucil and phenylacetic mustard were 0.021 and 0.013, respectively. Melphalan demonstrated a biphasic disappearance from plasma, with half-lives of 1.9 and 78 min. The compound was approximately 86% plasma protein-bound. Low concentrations of melphalan were detected in the brain, and its brain:plasma ratio was 0.13. These data demonstrate that following the administration of chlorambucil and melphalan, only low concentrations of active drug are able to enter the brain. As a consequence, concentrations of both drugs that cause the complete inhibition of extracerebrally located tumor have no effect on those located within the brain. Further, the brain uptake of melphalan, although low, is greater than that of chlorambucil and its active metabolites, which coincides with its slightly greater intracerebral activity following the systemic administration of very high doses. PMID- 3342461 TI - Membrane transport changes in an adriamycin-resistant murine leukemia cell line and in its sensitive parental cell line. AB - Multidrug resistance in cancer chemotherapy occurs when cells develop resistance towards structurally and functionally unrelated drugs. It is speculated that alteration of some fundamental process(es) in the cells leads to the development of multidrug resistance. The sodium pump activity of murine leukemia cell lines P388/S (sensitive) and P388/ADR (resistant) was measured and found to be different in the two cell lines. The rate of sodium pumping, i.e., the ouabain sensitive rubidium uptake, was consistently lower in the resistant cells compared to their parental controls. Uptake of adriamycin was lower in the resistant cells. Depolarizing the cells with potassium chloride or by inhibiting the pump with ouabain increased the adriamycin uptake in the sensitive cells but not in the resistant cells. Adriamycin did not have any acute effects on the sodium pump activity. It is concluded that the development of drug resistance in cell line P388 is associated with a decrease in sodium pump activity and a lack of depolarization-induced adriamycin uptake; these processes may be causally linked via alterations in cytosolic calcium concentration. PMID- 3342463 TI - Application of a new preclinical drug screening system for cancer of the large bowel. AB - We report a prospective evaluation of three human, continuous colorectal cancer cell lines and a new semiautomated radiometric technique (Bactec system) as a primary screening procedure for cytotoxic compounds with activity against cancer of the large bowel. COLO 320DM, Ht-29, and the metastatic OM-1 colon cancer cell line that have previously been shown to yield clinically relevant information in terms of drug sensitivity patterns in humans were all tested against 11 new compounds currently being investigated in phase I or early phase II clinical trials. Our results suggest that trimetrexate, DUP-785, didemnin B, and flavone-8 acetic acid may be clinically effective for the treatment of colorectal cancer. PMID- 3342462 TI - The effects of verapamil and a tiapamil analogue, DMDP, on adriamycin-induced cytotoxicity in P388 adriamycin-resistant and -sensitive leukemia in vitro and in vivo. AB - DMDP [N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl-m-dithane- 2-propylamine] a recently developed calcium antagonist analogue, caused a greatly increased intracellular retention of adriamycin and concomitant enhanced cytotoxicity in adriamycin-resistant P388 leukemia cells in vitro. These effects of DMDP were greater than those of another calcium channel blocker, verapamil, and occurred at one-half the dosage levels. Only slight enhancement in adriamycin toxicity was observed for either of these agents in the adriamycin-sensitive parental cell line. However, no significant therapeutic potentiation of adriamycin activity occurred with either verapamil or DMDP treatment in vivo. In vivo maximum DMDP tumor intracellular concentrations, as analyzed by HPLC, were the same in vitro tumor cell levels required to overcome adriamycin resistance. This inability to overcome drug resistance in vivo at acceptable levels of host toxicity is not only a function of maintaining necessary calcium antagonist concentrations in resistant tumor cells. PMID- 3342465 TI - Very high-dose cisplatin-induced ototoxicity: a preliminary report on early and long-term effects. AB - Acute and subacute audiometric hearing changes were evaluated in 12 patients receiving 35 courses of very high-dose (vhd) cisplatin (200 mg/m2 per course) in hypertonic saline at 4 or 8-week intervals. Audiogical evaluations were performed both before and immediately after each course of chemotherapy, and again after the discontinuation of treatment. A significant drop of the mean hearing threshold (P less than 0.01) at high frequencies was observed even within 48 h from the end of the first course of therapy, with 50% of the patients presenting a hearing loss of more than 15 dB. At the same total dose (200 mg/m2), one course of this regimen provided an incidence of hearing loss of more than 15 dB, which was four times greater than that reported with two courses of standard-dose regimens. The incidence and severity of the hearing impairment progressed further with subsequent courses of chemotherapy. Compared with baseline levels, most patients (75%) receiving at least two courses had a moderate to severe hearing loss, especially involving 4 and 8 kHz. At the end of treatment, 33% of the patients complained of a nondisabling functional hearing impairment. No recovery occurred after chemotherapy had been discontinued for 9-28 weeks. At this dose level cisplatin is markedly ototoxic. The use of hypertonic saline and vigorous hydration are effective means of minimizing the risk of nephrotoxicity, but seem to have no effect on cisplatin-related ototoxicity. PMID- 3342464 TI - Phase 1 study of high-dose hydroxyurea in lung cancer. AB - The in vitro chemosensitivity of a human lung cancer cell line to hydroxyurea (HU) was measured, and concentrations of 1 mM HU effected 99% inhibition of cell growth. Therefore, infusions designed to achieve serum levels of over 1 mM HU were assessed by escalating doses of hydroxyurea (HU) administered by continuous i.v. infusion at 3-weekly intervals in 18 patients with lung cancer. Dose increments from 24 g in 24 h to 48 g in 48 h were achieved. The dose-limiting toxicity at 48 g in 48 h was myelosuppression. Oral administration of HU did not result in sustained levels comparable to those achieved with continuous infusion. Two patients showed evidence of radiological response after three courses of treatment. Serum HU profiles were monitored after administration i.v. in 26 courses and after administration p.o. in 5 courses of treatment. A mean serum level of greater than 1 mM was achieved by 6 h and then maintained during treatment. The standard error of the mean area under the curve showed an overall 5% variation. HU can be given in doses up to 48 g in 48 h 3-weekly with manageable tissue and bone marrow toxicity, and the in vivo blood levels attained are equal to those necessary for effective cell inhibition in an appropriate in vitro model. This schedule provides a basis for combination studies with other cytotoxics or for use of HU as a DNA repair inhibitor. PMID- 3342466 TI - Phase II study of divided-dose vinblastine in advanced breast cancer patients. AB - The pharmacokinetics of a 5-day, continuous infusion of vinblastine have been reproduced by an i.v. divided bolus at 0 and 48 h [10]; this schedule can be easily applied to outpatients. We treated 26 evaluable patients with refractory, advanced breast cancer with 3.5-4 mg/m2 vinblastine given i.v. by a divided bolus at 0 and 48 h of 21-day cycles. Neurotoxicity and myelosuppression were the main side effects: severe constipation and peripheral neurotoxicity developed in 14% and 3% of the patients, respectively; severe leukopenia and thrombocytopenia occurred in 24% and 10% of the patients, respectively. One partial response, 14 no changes, and 11 progressions were obtained. Our results do not support the use of vinblastine in divided doses in treating this disease. PMID- 3342467 TI - Chemotherapy for relapsed and resistant acute nonlymphoblastic leukemia. Effect of ATA, an amsacrine-containing regime. AB - Twenty-nine evaluable patients with acute nonlymphoblastic leukemia (ANLL), either in relapse or resistant to initial induction therapy (ara C, daunorubicin + etoposide), received the ATA regime consisting of 100 mg/m2 per day Ara C by i.v. infusion for 4-5 days, 100 mg/m2 per day thioguanine orally for 4-5 days, and 100 mg/m2 per day amsacrine i.v. for 2-5 days. Each patient received 1-6 courses (median, 2) of the regime. There were 7 (24%) complete responders, and their duration of responses were 2, 2, 2, 5, 9+, 19, and 24+ months. The complete remission (CR) rate of patients who had a previous CR beyond 6 months (6/13, 46%) was significantly better (X2 = 4.25, p less than 0.05) than that of those who had previously relapsed within 6 months or were refractory to primary induction chemotherapy (1/16, 6%). The two groups of patients had similar patterns of treatment failure. Myelosuppression was the major toxic side effect, and nonhematological toxicities were mild and acceptable. PMID- 3342468 TI - Antitumor effect of CPT-11, a new derivative of camptothecin, against pleiotropic drug-resistant tumors in vitro and in vivo. AB - CPT-11, a new derivative of camptothecin, was effective against tumor cells, especially vincristine (VCR)-and adriamycin (ADM)-resistant P388 leukemia, compared to either VCR or ADM. The drug showed superior chemotherapeutic effects over VCR and ADM in sensitive P388 leukemia-bearing mice, and was also effective in VCR- and ADM-resistant P388 leukemia-bearing mice. These latter survival advantages with CPT-11 were almost equal to those obtained by CPT-11 against sensitive P388 leukemia. CPT-11 was found to be effective against human tumor cells, especially various pleiotropically drug-resistant human tumor lines, compared to VCR and ADM. CPT-11 should be considered for further development as a new chemotherapeutic agent potentially effective against pleiotropically drug resistant tumors. PMID- 3342469 TI - Correlation between free platinum AUC and total platinum measurement 24 h after i.v. bolus injection of cisplatin in humans. AB - The plasma kinetics of platinum after i.v. bolus administration of cisplatin was determined for 17 patients with advanced cancer. Statistical analysis of individual values revealed a high correlation between the area under the plasma concentration-time curve (AUC) of free platinum (unbound to proteins) and the concentration of platinum bound to plasma proteins 24 h after drug administration (Cp24). A similar correlation was found between the peak plasma values of ultrafiltrable platinum (Cp0) and Cp24. When studied in the same patient, increases in free platinum AUC and Cp0 were also found to result in increased Cp24. It is suggested that a single measurement of plasma platinum concentration 24 h after i.v. infusion of cisplatin could be a simple method either of detecting patients with extreme values of AUC and Cp0 or of studying the evolution of these parameters during multiple courses of treatment, although it cannot be used to give precise values for AUC and Cp0. PMID- 3342470 TI - Pharmacokinetic and phase I study of intravenous DON (6-diazo-5-oxo-L-norleucine) in children. AB - DON (6-diazo-5-oxo-L-norleucine), a glutamine antagonist, has been subjected to limited clinical trials since 1957. Use of the drug in adults has been curtailed due to sparse reports of effectiveness as well as its dose-limiting toxicities, i.e., severe nausea, vomiting and mucositis. In earlier studies, children given DON orally in combination with 6-mercaptopurine had significant prolongation of remission of acute leukemias during maintenance therapy. As DON is acid-labile and relatively unstable in solution, oral administration does not appear to be ideal for DON. In the trial described in this report, i.v. DON therapy was studied, using i.v. chlorpromazine to control vomiting, in 20 children, 17 of whom were evaluable following treatment at DON dose levels ranging from 150 mg/m2 to 520 mg/m2. Nausea and vomiting, the dose-limiting toxicity for adults, was controlled with chlorpromazine. Mucositis, which has also been observed in adults, did not occur in the children given DON i.v. A maximum tolerated dose was not defined; however, the projected maximum tolerated dose appears to be in excess of 450 mg/m2. DON was measured in plasma using a rapid-sampling HPLC procedure. The total body clearance, plasma t1/2, and area under the plasma concentration curve (AUC) were calculated using a noncompartmental method. The drug is rapidly cleared from plasma (t 1/2 = 3 h), and its volume of distribution is approximately twice that of total body water in children. These pharmacokinetic data, differ from that of adults reported by others. Specifically, the plasma t 1/2 for children is longer: total body clearance (Cl), and volume of distribution at steady state (Vss) are greater. In addition, no dose dependency of t 1/2, Cl or Vss was observed in this study, and the DON pharmacokinetics were linear and predictable. Five of nine children with acute leukemia showed improvement, though insufficient for classification as partial response, and five of eight children with solid tumors also showed improvement. Further trials using DON in combination with thiopurines or other agents appear indicated. PMID- 3342471 TI - Positive direct antiglobulin test in a pediatric patient following high-dose cisplatin. AB - A positive direct antiglobulin test (DAT) and hemolytic anemia are uncommon side effect of cisplatin (CDDP) therapy. A 9-year-old girl treated for extraosseus Ewing's sarcoma with a multiagent regimen, including 200 mg/m2 CDDP preceded by vincristine (VCR) and cyclophosphamide (CY), developed a positive DAT, followed by hemolytic anemia. When CDDP therapy was discontinued, the DAT became negative and no signs of anemia were observed during the maintenance treatment, which included VCR and actinomycin D. PMID- 3342472 TI - Cytotoxic and antitumor effects of the norepinephrine analogue meta-iodo benzylguanidine (MIBG). AB - Meta-iodo-benzylguanidine (MIBG) is an analogue of the neurotransmitter norepinephrine. In its radioiodinated form, MIBG is clinically used as a tumor targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. The potential cytotoxicity of the unlabeled drug was tested. MIBG appeared cytotoxic in a large panel of histogenetically different cell lines without preference against tumor cells of neural origin. The cytotoxicity of MIBG was higher than of the related mono-amine precursor, meta-iodo-benzylamine (MIBA). Drugs that block adrenergic receptors and inhibitors of tyrosinase or tyrosine hydroxylase had no effect on the cytostatic properties of MIBG. However, its activity was potentiated by the pharmacological inhibition of catecholamine degradation and by inhibitors of intracellular storage. MIBG had anti-tumor effects on L1210 leukemia and N1E115 neuroblastoma, grown as subcutaneous tumors in animals treated with MIBG in non-toxic schedules. The observations suggest that MIBG is cytotoxic in its native form and may contribute by this property to the clinical responses obtained with the radiolabeled drug at high concentrations. PMID- 3342473 TI - Blood serum atherogenicity associated with coronary atherosclerosis. Evidence for nonlipid factor providing atherogenicity of low-density lipoproteins and an approach to its elimination. AB - To reveal the presence of atherogenic potential in the blood serum obtained from patients with angiographically assessed coronary atherosclerosis we used primary cultures of subendothelial cells isolated by collagenase from unaffected human aortic intima. Earlier, we have demonstrated that such cultures are made up mostly of typical and modified smooth muscle cells. Within 24 hours of cultivation with a 40% sera of patients suffering from coronary atherosclerosis, the total intracellular cholesterol level increased twofold to fivefold. Cultivation with the sera of healthy subjects had no effect on the intracellular cholesterol level. The sera of patients were separated by ultracentrifugation into two fractions: total lipoprotein fraction containing the main classes of lipoproteins and a lipoprotein-deficient fraction. The former, but not the lipoprotein-deficient fraction, was characterized by atherogenicity (i.e., the ability to induce the accumulation of intracellular cholesterol). Lipoproteins of the patients' serum were separated into main classes: low density lipoproteins (LDL), very low density lipoproteins (VLDL), and high density lipoproteins (HDL2 and HDL3). An atherogenic component of the serum capable of stimulating the deposition of intracellular cholesterol was represented by LDL and, in one case, by VLDL, but not by other classes of lipoproteins. LDL and other lipoproteins isolated from the blood serum of healthy subjects failed to raise the cholesterol content in cultured cells; that is, they were nonatherogenic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342474 TI - Adrenaline increases the rate of cycling of crossbridges in rat cardiac muscle as measured by pseudo-random binary noise-modulated perturbation analysis. AB - The mechanism of action of adrenaline on cardiac contractility in rat papillary muscles containing V1 and V3 isomyosins was analyzed during barium-activated contractures at 25 degrees C by frequency domain analysis using pseudo-random binary noise-modulated perturbations. The analysis characterizes a frequency (fmin) at which dynamic stiffness of a muscle is a minimum, a parameter that reflects the rate of cycling of crossbridges. We have previously shown that fmin for V1- and V3-containing papillary muscles were 2.1 +/- 0.2 Hz (mean +/- SD) (n = 10) and 1.1 +/- 0.2 Hz (n = 8), respectively, and that these values were independent of the level of activation. The present study's goal was to determine whether the inotropic action of adrenaline was associated with an increased rate of crossbridge cycling. The results show that a saturating dose of adrenaline increased fmin in V1 hearts by 49 +/- 2% (n = 11). The action on V3 hearts was significantly less; the increase in fmin was 26 +/- 2% (n = 6). The increase in fmin for V1 hearts was shown to be sensitive to the beta-blocking agent propranolol. These results suggest that adrenaline significantly increases the rate of crossbridge cycling by a beta-receptor-mediated mechanism. We conclude that the increased contractility of the heart in the presence of adrenaline arises not only from more complete activation of the contractile proteins but also from the increased rate at which each crossbridge can transduce energy. PMID- 3342475 TI - Vasa vasorum in atherosclerotic coronary arteries: responses to vasoactive stimuli and regression of atherosclerosis. AB - The goals of this study were to determine whether vasa vasorum in atherosclerotic coronary arteries respond to vasoactive stimuli and to examine effects of regression of atherosclerosis on blood flow through vasa vasorum in coronary arteries. We studied three groups of monkeys: normal, atherosclerotic, and regression. Blood flow to vasa vasorum was measured with microspheres. Blood flow to intima-media (ml/min x 100 g) was 5 +/- 1 (mean +/- SEM) in normal and 47 +/- 7 in atherosclerotic monkeys (p less than 0.05). Infusion of phenylephrine or serotonin did not alter flow through vasa in normal monkeys. In atherosclerotic monkeys, phenylephrine decreased flow through vasa vasorum in intima-media of coronary arteries to 24 +/- 4 (p less than 0.05), and serotonin decreased flow to 27 +/- 5 (p less than 0.05). In regression monkeys, blood flow to intima-media was sixfold less (7 +/- 2 ml/min x 100 g) than in atherosclerotic monkeys (p less than 0.05). During infusion of adenosine, blood flow to vasa was fourfold greater in atherosclerotic monkeys than after regression of atherosclerosis. This finding suggests that loss of vessels, not constriction of existing vessels, accounts for the decrease in flow through vasa in intima-media after regression of atherosclerosis. We conclude that vasa vasorum in atherosclerotic coronary arteries respond to vasoconstrictor stimuli and that there is loss of vasa vasorum and a large decrease in blood flow through vasa to intima-media of coronary arteries after regression of atherosclerosis. PMID- 3342476 TI - Changes in substrate metabolism and effects of excess fatty acids in reperfused myocardium. AB - The purpose of these studies was to characterize the rates of fatty acid oxidation in reperfused myocardium and test the influence of excess fatty acids (FA) on mechanical function in the extracorporeally perfused, working swine heart model. Seventeen animals were prepared. Eight were untreated (LOW FA group; serum FA averaged 0.55 +/- 0.07 mumol/ml) and nine received a constant infusion of 10% Intralipid with heparin to raise serum FA to about 1.4 +/- 0.21 mumol/ml (HIGH FA group). Coronary flow in both groups was held at aerobic levels for an equilibrium period of 40 minutes, acutely reduced regionally in the anterior descending circulation by 60% for 45 minutes, and acutely restored to aerobic levels for 60-minute reflow. Appreciable mechanical depression (-47 delta% from aerobic values; p less than 0.01) during reperfusion was noted in both groups. This was associated with modest reductions in myocardial oxygen consumption (p less than 0.05) and losses of total tissue carnitine stores (p at least less than 0.02). Reperfused myocardium showed a strong preference for and aerobic use of FA during reflow such that 14CO2 production from labeled palmitate exceeded preischemic levels (+89 delta% in LOW FA hearts; +111 delta% in HIGH FA hearts). This suggested relative preservation of restoration of certain elements in mitochondrial function during reflow. The findings argue for uncoupling between substrate metabolism and energy production, accelerated but useless energy drainage, or some impairment between energy transfer and function of contractile proteins as possible explanations for the persistent depression of mechanical function (stunning) during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342477 TI - Role of the left atrium in adaptation of the heart to chronic mitral regurgitation in conscious dogs. AB - The manner in which the left atrium adapts to chronic mitral regurgitation and the role of the adapted left atrium as a modulator of excessive central blood volume were analyzed in seven conscious dogs, instrumented with high-fidelity pressure transducers and ultrasonic dimension gauges for measurement of left atrial and left ventricular pressure and cavity size. After obtaining data in a control situation, mitral regurgitation was produced by transventricular chordal sectioning. Heart rate was matched by right atrial pacing. In the "early" stage (7-14 days), left ventricular end-diastolic and mean left atrial pressures increased from 6 to 16 mm Hg and from 4 to 12 mm Hg, respectively. Both left ventricular end-diastolic segment length and left atrial diameter prior to atrial contraction increased by 7%. In the "late" stage (20-35 days), despite significant decreases in left ventricular filling pressure (11 mm Hg) and left atrial pressure (8 mm Hg), there was a continuous increase in left ventricular end-diastolic dimension (10%) and atrial end-diastolic diameter (10%). After the onset of mitral regurgitation, the left atrium performed greater work with a more enlarged cavity. Left atrial chamber stiffness was progressively decreased. These changes were associated with progressive increase in the left atrial diameter at zero stress, and there was a significant increase in the diameter of the left atrial myocyte. These results indicate that during chronic mitral regurgitation, the left atrium enlarges in size and mass, with a more potent booster action. The left atrial chamber becomes more compliant. Thus, the enlarged left atrium appears to exert an important compensatory mechanism in the case of excessive central blood volume by buffering pressure rise in the atrium and by providing an adequate ventricular filling volume. PMID- 3342478 TI - Electrophysiological effects of acute ventricular dilatation in the isolated rabbit heart. AB - We examined the effects of left ventricular dilatation on epicardial pacing threshold, conduction velocity, and effective refractory period (ERP) in the isolated, retrograde perfused rabbit heart. Left ventricular size was modified by acutely changing the volume of a fluid-filled balloon anchored within the vented left ventricle. Increases in left ventricular volume, associated with increases in left ventricular end-diastolic pressure from 0 +/- 1 to 35 +/- 2 mm Hg, were not associated with significant changes in pacing threshold or conduction velocity. The left ventricular ERP decreased significantly with an added volume of 1.5 ml (91.4 +/- 5.5 msec) compared with starting volume (117.7 +/- 3.8 msec, p less than 0.01). Right ventricular ERP did not change significantly with increases in left ventricular volume. The left and right ventricular ERPs were comparable at starting volume (117.7 +/- 3.8 and 117.6 +/- 3.5 msec, respectively; p = NS) but were significantly different with an added volume of 1.5 ml (91.4 +/- 5.5 and 112 +/- 5.6 msec, p less than 0.05). These changes were independent of coronary perfusion pressure and paced cycle length, suggesting that ischemia is an unlikely explanation for the observed effects. Changes in left ventricular volume decreased left ventricular ERP in a regionally heterogeneous manner, increasing the temporal dispersion of recovery over the left ventricle nearly twofold. Induced ventricular arrhythmias (ventricular tachycardia or fibrillation) were significantly more frequent at high (35%) than at low (3%) volumes during left ventricular pacing. We conclude that ventricular dilatation is associated with increased dispersion of refractoriness in this model, a finding that correlates with propensity for reentrant arrhythmias. PMID- 3342479 TI - Effects of left ventricular loading by negative intrathoracic pressure in dogs. AB - There are many factors, both intrinsic and extrinsic to the left ventricle, that can affect its function when negative intrathoracic pressure is imposed. In this study, we examined whether the left ventricular response to the afterload imposed by negative intrathoracic pressure was similar to that imposed by partial aortic constriction. We used steady-state right heart bypass to control pulmonary venous return to the left ventricle and reflex blockade to maintain constant heart rate and contractility. To impose negative intrathoracic pressure we used a pressure chamber fitted over a midsternal thoracotomy, which allowed steady negative pressure to be applied to all intrathoracic surfaces. Left ventricular volumes were measured from biplane cineradiograms of multiple 1-mm markers implanted in the left ventricular midwall. With cardiac output and heart rate constant, we compared the left ventricular response to two different levels of negative intrathoracic pressure and to increasing aortic pressure by partial aortic constriction. In each case, negative intrathoracic pressure produced a rise in the left ventricular end-systolic and end-diastolic volumes as well as transmural pressures similar to the effects of partial aortic occlusion. Thus, when cardiac output, heart rate, and contractility are maintained constant and all external restraints on the left ventricle are removed, the left ventricle responds in a similar manner to an increase in hydraulic load whether produced by a decrease in intrathoracic pressure or by partial aortic occlusion. PMID- 3342480 TI - Skinned fibers of human atrium and ventricle: myosin isoenzymes and contractility. AB - Different myosin isoenzymes of pig and human atrium and ventricle and rat ventricle were characterized by two approaches: pyrophosphate polyacrylamide gel electrophoresis (PP-PAGE) and analysis of the myosin P light chains by two dimensional polyacrylamide gel electrophoresis (2D-PAGE). We further investigated the relation between atrial and ventricular myosin isoenzymes of human, pig, and rat, and the maximum (unloaded) shortening velocity (Vmax) and the Ca2+ sensitivity of chemically skinned fibers of the same species. The myosin isoenzymes of both human and pig atrium comigrated in the PP-PAGE with rat V2 isomyosin, whereas the ventricle of human and pig comigrated with rat V3. In both human and pig ventricle, a myosin P light chain polymorphism exists (two phosphorylatable P light chains with the same molecular weight but different isoelectric points). In contrast, we found no P light chain polymorphism in the atrium of human and pig and in the ventricle of rat (one phosphorylatable P light chain only). A correlation exists between Vmax, Ca2+ sensitivity, and atrium- and ventricle-specific myosin isoenzymes of human and pig. Vmax was determined by the slack-test method. Plots of delta l versus delta t of atrial and ventricular skinned fibers were well fitted by a single straight line up to delta l = 15% and delta l = 13%, respectively. Vmax of skinned ventricular fibers was lower than Vmax of skinned atrial fibers in both human and pig. Ca2+ sensitivity of skinned fibers of ventricle, however, was higher than Ca2+ sensitivity of atrial skinned fibers in both human and pig. PMID- 3342481 TI - PQRST isoarea maps from patients with the Wolff-Parkinson-White syndrome: an index for global alterations of ventricular repolarization. AB - Isoarea maps during the PQRST sequence were computed in 22 healthy subjects and 48 patients with Wolff-Parkinson-White (WPW) syndrome. Thirty-eight patients with WPW were on no medication and 10 were treated with class I, II, or III antiarrhythmic drugs. Seventeen isoarea maps were recorded before and 17 were recorded after accessory pathway ablation. One patient had intermittent preexcitation. Body surface maps from all healthy subjects were similar, although the magnitudes of the maxima and minima showed significant variability. In all patients with WPW who were on no medication and in those on class I and II agents, PQRST maps were normal. Two patients taking amiodarone had abnormal PQRST maps, as did patients early after surgery. In the patient with intermittent preexcitation, PQRST maps were very similar during normal and preexcited beats. In conclusion, our results support the theory that the PQRST time integral reflects intrinsic recovery properties of the heart and is independent of the activation sequence. PMID- 3342482 TI - Does normal pump function belie muscle dysfunction in patients with chronic severe mitral regurgitation? AB - Left ventricular cineangiography and micromanometry were performed simultaneously in 27 patients with chronic severe mitral regurgitation (MR group) and in 23 normal subjects (NL group). Stress (sigma) and volume (V) were computed frame by frame. Measurements were repeated after pharmacologic load manipulation in subsets of MR (n = 10) and NL (n = 11) groups. An inverse relationship (r = -.90) between EFc (ejection fraction determined from a common preload) and sigma es (afterload) was observed for the NL group. For the MR group, 10 of 14 with EFs less than 0.60 and four of 13 with EFs greater than 0.60 had muscle dysfunction, falling below the 95% prediction band of the normal EFc-sigma es relationship. Maximum myocardial stiffness (maxEN) determined from the end-systolic stress strain relationship of Mirsky, sigma es = maxEN.gamma.loge(Ves/Vo), was 1398 +/- 716 in the MR (n = 10) vs 1165 +/- 394 in the NL group (n = 11, NS). EF was 0.62 +/- 0.13 in the MR and 0.65 +/- 0.08 in the NL group. Mitral valve surgery was performed on 19 of the patients with MR. All survived and all but one were symptomatically improved; that patient required reoperation in the early postoperative period because of transverse midventricular disruption. Thus, contractile function as assessed by stress-strain and EFc-afterload relationships is frequently normal in individuals with MR when EF is normal. When EF is depressed, contractile function as assessed by EFc-afterload relationships is frequently depressed, but this does not preclude a satisfactory surgical result. PMID- 3342483 TI - The role of intracoronary thrombus in unstable angina: angiographic assessment and thrombolytic therapy during ongoing anginal attacks. AB - Intracoronary thrombus is regarded as a potentially important factor in the etiology of unstable angina, but the incidence of intracoronary thrombus in unstable angina has not been clearly defined. To determine the occurrence of intracoronary thrombus during ongoing angina pectoris, coronary angiography was performed during spontaneous ischemic attacks in 37 patients with prolonged rest angina. All patients exhibited significant (greater than 50%) stenoses of at least one major coronary artery. Of the 37 patients, 21 (57%) had intracoronary thrombus in major coronary arteries, whereas 14 (38%) had fixed narrowings without evidence of intracoronary thrombus and two exhibited coronary spasm. ST segment elevation was observed in 16 of 21 patients with thrombus and in all of the patients with coronary spasm, but all the patients with organic stable obstruction showed ST segment depression. Twenty of the 21 patients with thrombus improved after thrombolytic therapy with intracoronary injection of urokinase; obstructed arteries were reopened, or narrowings were attenuated, with relief of ischemic symptoms. In patients with fixed obstructions, the rate-pressure product during active symptoms was significantly higher than during an asymptomatic period, indicating that a transient increase in myocardial oxygen demand may contribute to the ischemic attack in these patients. A high incidence (71%) of recurrent symptoms was observed in patients with intracoronary thrombus even after successful thrombolysis, in contrast to a much lower incidence (36%) in those without intracoronary thrombus. Myocardial infarction within 4 weeks after catheterization was observed more frequently in patients with intracoronary thrombus (24%) than in those without thrombus (7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342485 TI - Differing mechanisms of exercise flow augmentation at the mitral and aortic valves. AB - To determine the mechanisms by which blood flow increases across the mitral and aortic valves during exercise, 18 normal men were studied during graded supine and upright bicycle exercise at matched workloads. Mitral valve orifice and ascending aortic blood velocities were recorded by Doppler echocardiography during steady states at each stage of exercise. Parasternal two-dimensional echocardiographic imaging of the ascending aorta adjacent to the aortic valve orifice and the mitral valve orifice at the tips of the valve leaflets was used to calculate changes in cross-sectional area during exercise. Heart rate increased from rest to exercise from 67 to 150 beats/min (124%) during supine exercise and from 72 to 147 beats/min (104%) during upright exercise. Stroke volume increased 20% during supine and 46% during upright exercise; the increase in stroke volume was statistically significant when rest and exercise were compared and when the magnitude of change was compared vs position (p less than .05). The increase in stroke volume measured at the ascending aorta was accomplished by an increase in the velocity-time integral (+15% supine and +48% upright, p less than .05), with little change in aortic cross-sectional area (5% supine and 0% upright, p = NS). By contrast, the increase in flow rate measured at the mitral valve was predominantly due to an increase in mean diastolic cross sectional area (+29% supine and 34% upright, p less than .05); the velocity-time integral did not increase significantly (-10% supine and 4% upright; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342484 TI - Multivessel coronary spasm in patients with variant angina: a study with intracoronary injection of acetylcholine. AB - Multivessel coronary spasm has been described but its incidence in patients with variant angina still remains unclear. Thirty-three patients with variant angina were studied during coronary angiographic examination with selective intracoronary injection of acetylcholine (ACh). In all but three patients, the location of ischemia during attack was determined by the electrocardiographic findings, by exercise 201Tl myocardial scintigraphy, and by two-dimensional echocardiography during a hyperventilation test, and the coronary artery (or arteries) responsible for the attack was predicted before the study. ACh induced spasm of at least one coronary artery in all but one patient. ACh induced spasm of both the left and right coronary arteries (i.e., multivessel coronary spasm) in 24 patients: in two of the four patients who were predicted to have spasm of the left coronary artery, in six of the 11 predicted to have spasm of the right coronary artery, in 13 of the 15 predicted to have spasm of both the left and right coronary arteries, and in three of the three in whom coronary artery responsible for attack had not been predicted. This ACh-induced spasm of the left and right coronary arteries occurred separately and no patients showed hemodynamic instability during attack. In one patient in whom multivessel coronary spasm had been predicted and ACh failed to induice coronary spasm, ergonovine maleate (0.2 mg) induced spasm of both the left and right coronary arteries simultaneously, resulting in severe prolonged hypotension. Nineteen of the 25 patients in whom multivessel coronary spasm was documented showed angiographically normal or nearly normal coronary arteries after administration of nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342486 TI - Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities. AB - This study was designed to determine the pathophysiologic basis of increased exercise ventilation in the presence of chronic heart failure. Sixty-four ambulatory patients with chronic heart failure and 38 age-matched normal control subjects performed exercise according to identical staged, symptom-limited bicycle exercise protocols with measurement of hemodynamic, ventilatory, and metabolic responses. Compared with normal subjects, ventilation and the ratio of ventilation to CO2 production (Ve/VCO2), and pulmonary capillary wedge pressure were elevated in patients at rest and during exercise. The ratio of pulmonary dead space to tidal volume (Vd/Vt) also was elevated in the heart failure group at rest and during exercise and was closely related to Ve/VCO2 (all r greater than .72, p less than .001). Rest and exercise arterial PCO2 regulation was normal in patients. Peak exercise Ve/VCO2 did not correlate with pulmonary vascular pressures, but was inversely related to cardiac output (r = -.49, p less than .001). Thus, neurohumoral ventilatory control mechanisms are intact in patients with chronic heart failure and act to maintain normal PaCO2 levels in the face of increased pulmonary dead space. Activation of abnormal reflexes due to hemodynamic derangements during exercise are not important in determining ventilation in the presence of chronic heart failure. The demonstration of a correlation between decreased cardiac output and increased ventilation in the patient group suggests that attenuated pulmonary perfusion may play a role in causing exercise hyperpnea in the presence of chronic heart failure by producing ventilation perfusion abnormalities and thereby increasing physiologic pulmonary dead space. PMID- 3342487 TI - Idiopathic sustained left ventricular tachycardia: clinical and electrophysiologic characteristics. AB - Electrophysiologic studies were performed in 16 patients 11 to 45 years old (mean 33 years) with idiopathic sustained (lasting more than 5 min) ventricular tachycardia (VT) originating from the left ventricle. Endocardial mapping during VT showed that the earliest site of activation was at the apical inferior portion of the left ventricle in 14 patients whose QRS morphology during VT showed a right bundle branch block pattern and left-axis deviation, but at the apical anterosuperior portion of the left ventricle in two patients whose QRS morphology during VT showed a right bundle branch block and right-axis deviation. Single programmed ventricular stimulation induced VT in 13 patients, and rapid ventricular pacing induced VT in the remaining three patients. Rapid ventricular pacing terminated VT in all patients. The relationship between the coupling interval and the echo interval was inverse in all eight patients with a wide VT inducible zone. Entrainment was recognized in three of six patients. The initiation of VT by constant pacing depended on the number of pacing beats but not the duration of pacing in all four patients tested. Intravenous verapamil terminated the VT in 13 of 14 patients. Long-term oral verapamil was also effective in all five patients who required long-term oral therapy for their symptoms associated with VT. In conclusion (1) idiopathic left ventricular tachycardia has unique electrocardiographic, electrophysiologic, and electropharmacological properties, (2) the electrophysiologic characteristics suggest that the mechanism is reentry, and (3) verapamil is effective in both the short- and long-term treatment of VT. PMID- 3342488 TI - Entrainment of ventricular tachycardia: explanation for surface electrocardiographic phenomena by analysis of electrograms recorded within the tachycardia circuit. AB - Transient entrainment was demonstrated during 59 pacing events in 18 episodes of sustained uniform ventricular tachycardia (VT) while recording electrograms from the site of origin of tachycardia (LE-SOO). During entrainment, the morphology of the initial component of the LE-SOO was identical to the morphology observed during the tachycardia in 13 VTs (group I), but in five VTs (group II), the initial component changed at a "critical" paced cycle length. The presence of the proposed surface electrocardiographic criteria for entrainment--fixed fusion and a first postpacing complex without fusion but occurring at the paced cycle length -were integrally dependent on the morphologic changes in the local presystolic electrogram. Fixed fusion of the surface electrocardiogram at one or more paced cycle lengths was detected during entrainment at 35 of 59 paced cycle lengths in 12 of 18 tachycardias, 10 of which were group I and two of which were group II VTs. Fixed fusion demonstrated by analysis of the LE-SOO was observed at one or more pacing cycle lengths in 17 of 18 VTs. In five tachycardias in which surface electrocardiographic fusion was not observed, fixed fusion was evident on analysis of the left ventricular LE-SOO during right ventricular pacing. The first postpacing interval, as measured at the surface electrocardiogram, was consistently equal to the paced cycle length in only one of 18 tachycardias and was greater than the VT cycle length in eight of 17 tachycardias. A pathway with a long conduction time was demonstrated during entrainment. However, in those 12 VTs in patients in whom pacing was performed at more than one cycle length and there was preservation of the LE-SOO morphology, the conduction time between the stimulus and presystolic electrogram remained constant. Thus, no evidence for "atrioventricular nodal-like" decremental conduction was observed over a wide range of pacing cycle lengths. We conclude that: (1) two of the previously proposed criteria for diagnosis of entrainment (fixed fusion on the surface electrocardiogram and a first postpacing interval equal to the paced cycle length) are overly restrictive criteria for definition of "entrainment" of VT, (2) analysis of endocardial recordings from the site of origin of tachycardia during attempted entrainment of VT is useful for documenting the presence of entrainment, and (3) such analysis provides a basis for the understanding of surface electrocardiographic phenomenon associated with entrainment. PMID- 3342489 TI - Resetting of ventricular tachycardia with electrocardiographic fusion: incidence and significance. AB - The incidence and significance of fusion of the QRS complex during resetting of sustained ventricular tachycardias (VTs) was determined in 53 VTs induced by programmed stimulation in 46 patients with prior myocardial infarction. All 53 VTs were reset with one or two extrastimuli delivered at the right ventricular apex (RVA); 29 (54.7%) demonstrated fusion of the VT QRS complex coincident with the extrastimulus resetting the VT. Activation time at the RVA during VT (measured from the onset of the VT QRS complex to the first rapid deflection of the RVA electrogram) was longer in VT reset with fusion compared with those without fusion (91 +/- 30 vs 33 +/- 32 msec; p less than .001). A right bundle branch block VT QRS morphology and a rightward and inferior axis were more common in VT reset with electrocardiographic (ECG) fusion. Additionally, the shortest return cycle following the extrastimulus resetting the VT was shorter in VT reset with ECG fusion compared with those without (327 +/- 66 vs 423 +/- 84 msec; p less than .001). Fusion of the endocardial electrogram recorded at the site of VT origin was noted in 11 of 15 VTs that were reset while a recording catheter was positioned at this site, including all eight VTs with evidence of surface ECG fusion and three of seven VTs without fusion. Seventeen VTs were reset from the right ventricular outflow tract as well as the RVA; eight demonstrated QRS fusion at both sites, five from the right ventricular outflow tract only, and four from neither site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342490 TI - Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation. AB - In this report we describe electrophysiologic and histologic findings in hearts and endocardially resected preparations from patients with sustained ventricular tachycardias in the chronic phase of myocardial infarction. We recorded simultaneously from 64 endocardial sites during tachycardia in 72 patients that were operated on for medically intractable ventricular tachycardias. Two other patients underwent heart transplantation, and mapping was performed on the explanted isolated heart connected to a Langendorff perfusion set-up. During operation 139 tachycardias with different morphologies could be induced. Although the majority of evidence supports the concept of a reentrant mechanism for these tachycardias, we found that 105 tachycardias appeared to arise at a focal area of less than 1.4 cm2. In only three cases macroreentry around the infarction scar could be detected. Of 21 tachycardias in which the "origin" appeared to be focal, earliest subendocardial activation was preceded by discrete electrograms of low amplitude (presystolic activity). In three tachycardias presystolic activity was detected at several sites, permitting reconstruction of its route. Histology of the endocardial resected preparation in one of these cases revealed separate zones of viable myocardial fibers in areas in which presystolic activity was recorded. These zones were located intramurally and subendocardially, supporting the concept that reentry occurred via isolated bundles of surviving myocytes at the border of the infarct and the larger subendocardial muscle mass. Conduction velocity through the isolated tracts was on the order of 25 cm/sec. Similar reentrant pathways were found in the two isolated hearts. Extracellular and intracellular recordings were made from 20 endocardial preparations that were excised from areas in which tachycardia originated. Preparations were superfused in a tissue bath. These experiments showed that action potentials were usually close to normal, but occasionally action potentials with reduced amplitude and slow upstrokes were found. In addition, there were cells that exhibited both fast and slow upstrokes, depending on the direction of the wavefront. Histology of seven resected preparations and the isolated hearts showed subendocardially as well as intramurally located zones of viable myocardium. Fractionation of extracellular electrograms and slow conduction were found in areas where surviving muscle fibers and strands of fibrous tissue were interwoven, and in zones where muscle fibers were oriented in parallel but isolated by strands of connective tissue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3342491 TI - The relationship between left ventricular systolic function and congestive heart failure diagnosed by clinical criteria. AB - There is no uniformly accepted clinical definition for congestive heart failure (CHF), although criteria have been published by various groups. There is also no reference standard for CHF, although left ventricular ejection fraction (LVEF) gives a quantitative assessment of systolic function and is useful in predicting prognosis. To determine the relationship between LVEF and clinically diagnosed CHF, we compared resting LVEF determined by radionuclide ventriculography with diagnosis of CHF by clinical criteria in 407 patients, based on clinical data collected by a cardiology fellow. Of 153 patients with a low LVEF (less than or equal to 0.40), 30 (20%) met none of the criteria for CHF. Conversely, of 204 patients with normal LVEF (greater than or equal to 0.50), 105 (51%) met at least one of the criteria. We conclude that different criteria for CHF will have varying utility depending on the population being examined, and that a combination of clinical features and an objective measure of cardiac performance is needed to diagnose CHF. PMID- 3342492 TI - Abnormal exercise hemodynamics in patients with normal systolic function late after aortic valve replacement. AB - We studied the hemodynamic response to supine bicycle exercise in 20 patients late (10 +/- 2 years) after aortic valve replacement (for aortic stenosis in 12 patients, aortic insufficiency in six patients, and for combined stenosis and insufficiency in two patients). The pulmonary artery wedge pressure was obtained with a pulmonary artery balloon catheter, and left ventriculography was performed by digital-subtraction angiography after injection of radiographic contrast into the pulmonary artery. These patients were compared with 11 control subjects with no or minimal cardiac disease studied routinely for evaluation of chest pain in whom left ventricular end-diastolic pressure and a direct contrast ventriculogram were obtained. Compared with the control population, the study population had similar left heart filling pressures (7 +/- 3 vs 9 +/- 3 mm Hg, NS), but higher left ventricular ejection fractions (75 +/- 7% vs 67 +/- 7%, p less than .02) and higher left ventricular muscle mass indexes (106 +/- 28 vs 85 +/- 9 g/m2, p less than .01). Elevated myocardial muscle mass led to lower systolic wall stress in the study population than in the control subjects (254 +/- 65 vs 320 +/- 49 10(3).dynes/cm2, p less than .01) and might explain the higher ejection fraction observed. Fourteen patients had a normal response to exercise (with left heart filling pressures of 16 +/- 4 vs 18 +/- 2 mm Hg for control subjects, NS; and left ventricular ejection fraction of 77 +/- 8% vs 73 +/- 5% for control subjects, NS). However, while the remaining six patients had a normal exercise left ventricular ejection fraction (72 +/- 9%, NS), they had an abnormal rise in left heart filling pressure (33 +/- 8 mm Hg, p less than .01). Preoperatively these patients also had higher left ventricular mid- and end-diastolic pressures at similar diastolic volumes, suggesting a decrease in chamber compliance. Thus, late after aortic valve replacement there is a subgroup of patients who, despite normal hemodynamics and normal left ventricular systolic function as assessed by the left ventricular ejection fraction at rest, have an abnormal response to exercise characterized primarily by a substantial rise in left heart filling pressures. Preoperatively this group also has a decrease in diastolic chamber compliance despite nearly normal left ventricular ejection fractions. This abnormality appears to result from a primary derangement of diastolic function that is not evident at rest. PMID- 3342494 TI - Contractile dysfunction and ATP depletion after transient calcium overload in perfused ferret hearts. AB - Although a number of lines of evidence hint that an elevation of intracellular calcium leads to myocardial injury, the cellular consequences of transient Ca overload remain unclear. To determine the contractile, histologic, and metabolic sequelae of transient Ca overload, we measured developed pressure (DP) in isovolumetric Langendorff-perfused ferret hearts at 37 degrees C before and 20 min after three 5 min periods of perfusion with a 10 mM [Ca]o, 1 mM [Mg]o solution (high-Ca group, n = 8) without ischemia, and in control hearts (n = 5) exposed transiently to the same total divalent cation concentration without a change in [Ca]o (9 mM [Mg]o, 2mM [Ca]o). DP, measured at various [Ca]o (0.5 to 5 mM), was depressed in the high-Ca group relative to control (p less than .001). Representative hearts from the control group were histologically normal, whereas hearts from the high-Ca group exhibited rare foci of predominantly "reversible" injury (mitochondrial swelling, glycogen deposition, and clumping of nuclear chromatin). Maximal Ca++-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was also decreased in the high-Ca group (230 +/- 4 vs 262 +/- 6 mm Hg, p less than .001). Cao sensitivity, determined by normalization of the DP-[Ca]o relationship to the corresponding MCAP, was shifted to higher [Ca]o in the high-Ca group. Phosphorus nuclear magnetic resonance spectra were obtained in four high-Ca hearts. [ATP] declined by 30% to 40% after exposure to high [Ca]o, but inorganic phosphate, phosphocreatine, and pH remained unchanged. These results indicate that transient exposure to high [Ca]o without ischemia leaves behind distinctive contractile, metabolic, and histologic sequelae. The possible implications for the pathogenesis of postischemic contractile dysfunction are discussed. PMID- 3342493 TI - Physiologic mechanisms governing hemodynamic responses to positive inotropic therapy in patients with dilated cardiomyopathy. AB - Clinical trials in patients with dilated cardiomyopathy (DCM) have shown a wide disparity in the hemodynamic responses to positive inotropic therapy. In addition, the response of the failing left ventricle to positive inotropic agents reflects the net interaction of multiple factors, including the magnitude of contractile abnormality and compensatory mechanisms. In the current study, left ventricular geometry, loading conditions, and contractile state were assessed in 13 patients with nonischemic DCM with the use of simultaneous high-fidelity pressure measurements and echocardiographic recordings. Comparisons were made with echocardiographic and calibrated carotid pulse data acquired in nine age matched normal subjects. The patients with DCM were divided according to the left ventricular end-diastolic wall thickness-to-dimension ratio into groups with "appropriate" hypertrophy (i.e., less than or equal to 2 SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e., greater than 2 SDs from mean normal; n = 8; group 2). Age, New York Heart Association functional class, left ventricular wall mass index, and left ventricular end-diastolic pressure and dimension were similar for the DCM groups. Baseline left ventricular afterload (defined as circumferential end-systolic wall stress, sigma es) was 168% and 203% greater than normal in groups 1 and 2, respectively. The administration of the beta-adrenoceptor agonist dobutamine decreased left ventricular afterload by 12% in the normal subjects and by 10% in group 1 patients, while augmenting afterload by 5% in group 2 patients. The latter response occurred despite a 17% fall in systemic vascular resistance. Overall left ventricular performance, as assessed by the rate-corrected mean velocity of fiber shortening (Vcfc), was related to left ventricular afterload (i.e., sigma es). The resultant sigma es -Vcfc relationship, a sensitive measure of left ventricular contractility, was determined over a wide range of afterload conditions generated by methoxamine (normal subjects) or nitroprusside (DCM). Baseline left ventricular contractile state was 61% of normal for group 1 and 44% of normal for group 2. The contractile response to dobutamine infusion was 52% of normal for group 1 and only 22% of normal for group 2. Thus, positive inotropic therapy with dobutamine in patients with DCM is limited by (1) an attenuated contractile response and (2) elevated left ventricular afterload, which may be augmented further during its administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342495 TI - Comparative effects of nitroprusside and pinacidil on myocardial blood flow and infarct size in awake dogs with acute myocardial infarction. AB - The effect of nitroprusside in limiting myocardial infarct was compared with that of pinacidil, a new antihypertensive agent with potent coronary vasodilator properties, in instrumented awake dogs subjected to 4 hr of left anterior descending coronary artery occlusion and 20 hr of reperfusion. Dogs were randomly assigned to receive intravenous normal saline, nitroprusside, or pinacidil beginning 40 min after the onset of coronary artery occlusion and continuing throughout the occlusion and the first hour of reperfusion. Nitroprusside and pinacidil were titrated to decrease mean aortic pressure by 25 mm Hg; normal saline had no effect on mean aortic pressure. Other systemic hemodynamic variables were not significantly altered by normal saline or nitroprusside, and myocardial blood flow did not change during normal saline infusion in normal and ischemic myocardium. In contrast, nitroprusside increased the blood flow and the endocardial/epicardial flow ratio in ischemic myocardium. This increase in ischemic myocardial blood flow was accompanied by a significant reduction in infarct size (40 +/- 3% of region at risk vs 58 +/- 4% in the normal saline group; p less than .05). Pinacidil increased heart rate, cardiac output, and the peak rate of rise of left ventricular pressure. Furthermore, despite causing a threefold to fourfold increase in normal myocardial blood flow, pinacidil had no effect on either blood flow to ischemic myocardium or infarct size (57 +/- 5%). The data indicate that the marked coronary vasodilator effect of pinacidil does not cause an increase in ischemic blood flow or a reduction in infarct size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342496 TI - Improvement in myocardial performance without a decrease in high-energy phosphate metabolites after isoproterenol in Syrian cardiomyopathic hamsters. AB - To determine the effect of isoproterenol on cardiac energetics and function in an animal preparation of cardiomyopathy, we studied Langendorff perfused hearts from Syrian cardiomyopathic hamsters. High-energy phosphate metabolites (phosphocreatine [PCr], ATP, inorganic phosphate [Pi]) and intracellular pH (pHi) were measured by 31P nuclear magnetic resonance spectroscopy and correlated with left ventricular developed pressure, coronary flow, and O2 consumption before and during a 10(-6)M infusion of isoproterenol. Total intracellular calcium was also determined by atomic absorption spectroscopy with the use of potassium ethylenediamine tetra-acetate cobaltate as a marker for extracellular space. In cardiomyopathic hamsters, isoproterenol infusion increased mean developed pressure by 300% (p less than .005 compared with control; n = 5), O2 consumption eightfold (p less than .0005), and PCr by 40% (p less than .05). PCr/Pi ratio, which is analogous to phosphorylation potential, improved 100% (p = .05). In normal hamsters, isoproterenol infusion resulted in an 83% increase in developed pressure (p less than .001) and a 25% increase in O2 consumption (NS). However, mean PCr and PCr/Pi decreased by 30% and 50%, respectively (p less than .05 for both), during isoproterenol infusion. pHi decreased in normal animals (p less than .01), but tended to improve in diseased animals (NS) during isoproterenol infusion. Freeze-clamp measurements of phosphate metabolites correlated well with the nuclear magnetic resonance data. Intracellular calcium increased from 0.0102 +/- 0.002 to 0.144 +/- 0.030 mumol/ml heart water in normal hamsters during isoproterenol infusion. Cardiomyopathic hamsters had a markedly elevated baseline calcium content of 60.82 +/- 5.85 mumol/ml heart water due to the presence of dystrophic calcification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342497 TI - Dietary guidelines for healthy American adults. A statement for physicians and health professionals by the Nutrition Committee, American Heart Association. AB - This statement for physicians replaces the American Heart Association's Dietary Guidelines for Healthy American Adults, published in 1986. The current guidelines propose an optimal preventive diet for coronary heart disease. Emphasis is placed on reduction of both saturated fat and total fat. Complex carbohydrates are recommended as the major replacement for calories from fat. Polyunsaturated and monounsaturated fats partially replace calories from other fat sources. Cholesterol and sodium guidelines are expressed with an upper limit on each. The use of alcohol as a possible means of preventing cardiovascular disease is not advised. Maintenance of recommended body weight by calorie control and physical activity is emphasized. PMID- 3342498 TI - The old order changeth. PMID- 3342499 TI - Mitral valvuloplasty at the Cleveland Clinic Foundation. PMID- 3342500 TI - Mortality and results after cardiac surgery in patients with end-stage renal disease. PMID- 3342501 TI - Making headway in enzyme standardization. PMID- 3342502 TI - Quantitative analysis for isoforms of creatine kinase MM in plasma by chromatofocusing, with on-line monitoring of enzyme activity. AB - Changes in the proportions of individual isoforms of the MM isoenzyme of creatine kinase (CK; EC 2.7.3.2) in plasma promptly reflect both myocardial infarction and coronary recanalization. However, quantitative methods developed thus far are too slow or cumbersome for routine use in making clinical decisions. We report a convenient, quantitative chromatofocusing assay with on-line fluorometric detection of isoform activity in the column eluent that provides results within 40 min from the time of sample application. Sample eluted from a microbore chromatofocusing column (1.8-mL bed volume) is split between a reaction stream, into which CK reagents are added, and a reference stream. After incubation at 37 degrees C, NADPH formed by reaction of isoforms with CK reagent is detected at 340 nm. The system can detect activity of individual isoforms in plasma samples having total CK activity greater than or equal to 21 U/L (30 degrees C). Results correlated closely with those obtained by previously validated, but slow, chromatofocusing (r = 0.98, n = 30) and protein immunoblotting (r = 0.90, n = 20) procedures. PMID- 3342503 TI - Differential precipitation of isolated human plasma lipoproteins with heparin and manganese chloride. AB - We studied the precipitation of isolated lipoproteins with heparin and MnCl2. Lipoproteins were isolated from human plasma by preparative ultracentrifugation and their free cholesterol was labeled. Each lipoprotein fraction was then precipitated at various pHs, with or without bovine serum albumin (60 g/L) present. Under no set of conditions was one class of lipoproteins completely separated from the other two. Specifically, under standard conditions for precipitation of serum lipoproteins (pH 7.4 and protein 60 g/L), 12% of the very low-density lipoprotein (VLDL) and 8% of the low-density lipoprotein (LDL) remained in the supernatant liquid, and 30% of the high-density lipoprotein (HDL) was precipitated. These results indicate that, under these conditions, so-called HDL cholesterol may be a mixture of VLDL, LDL, and HDL, although the sum of the amount of these three fractions remaining in the supernate is fortuitously very close to the value for HDL cholesterol isolated by ultracentrifugation. PMID- 3342504 TI - Use of alternative rules (other than the 1(2)s) for evaluating interlaboratory performance data. AB - Previous studies have documented the ineffectiveness of using either the group mean +/- 2 group standard deviations (SD) or the 1(2)s rule as the standard of acceptable performance in evaluating interlaboratory proficiency testing (PT) data. Using computer simulation of PT data, we evaluated the efficiency of 244 alternatives to the 1(2)s rule, all based on the PT population's mean and SD. Using the traditional interlaboratory PT format, we determined the ability of each rule to correctly identify both good and deficient intralaboratory performance. The rules are based on results from one to five PT samples "analyzed" at the same time. Because the effectiveness of the criteria set for acceptable performance in a PT program is influenced by the population SD, each rule's capabilities were examined for PT populations with interlaboratory SDs ranging from 1% through 10% of the population mean value. All rules achieve their maximum efficiency over a narrow range of interlaboratory SDs. For PT evaluations of intralaboratory performance to be optimally effective, selection of the rule must be based on the SD of the PT population. PMID- 3342505 TI - Comparing different statistical methods for evaluating diagnostic effectiveness of clinical tests: respiratory distress syndrome as a model. AB - Phospholipids in specimens of amniotic fluid from 346 patients were quantified and the results evaluated in light of the clinical outcome. Fifty-eight neonates had respiratory distress syndrome. We used this data base to compare different statistical methods for evaluating test effectiveness and diagnostic discrimination. Dichotomizing quantitative tests into binary tests with arbitrary cutoff values was inadequate for comparing test effectiveness. Subgrouping the data into deciles and calculating the incidence of respiratory distress syndrome for each decile avoided the problems of the preceding approach and was easy to calculate and comprehend; however, this method lacked statistical power. Relative operating characteristic curves yielded more statistical power, but results were more difficult to calculate and were not intuitively obvious to most workers in the laboratory. A modified cumulative frequency plot, combining elements of both decile subgrouping and relative operating characteristic curves, was easily calculated and intuitively obvious. These plots, like relative operating characteristic curves, provided an index for quantifying test effectiveness. When used in combination with standard cumulative frequency curves, they also provided direct diagnostic information on disease probability for any value of the clinical assay. PMID- 3342506 TI - What is the cause of benign transient hyperphosphatasemia? A study of 35 cases. AB - In a study of 35 children with benign transient hyperphosphatasemia, I found a marked seasonal clustering of cases after the summer months. Furthermore, plasma 25-hydroxyvitamin D concentrations were almost twice those of controls matched for age and time of year. Many children had evidence of weight loss and one had idiopathic hypercalcemia of infancy. Activities both of liver and bone isoenzymes of alkaline phosphatase (EC 3.1.3.1) in plasma were increased. The liver and (to a lesser extent) bone isoenzymes had enhanced electrophoretic mobility, and both showed increased binding to wheat-germ lectin by affinity electrophoresis. For the liver (and probably also the bone) isoenzyme, these changes were due to an increased content of sialic acid. A possible etiology for the condition is proposed involving (a) increased synthesis of alkaline phosphatase, mediated by vitamin D metabolites, and (b) decreased hepatic clearance caused by the high sialic acid content and exacerbated in some cases by the effects of some drugs on the liver. PMID- 3342507 TI - Radioenzymatic assay of catecholamines in plasma after a preliminary solvent extraction compared with an analogous liquid-chromatographic method. AB - Catechol-borate complexation and ion-pair formation combined with organic solvent extraction as preliminaries to radioenzymatic assay (REA) with catechol-O methyltransferase-catalyzed methylation allows the quantification of catecholamines in plasma samples of any volume. We attained improved detection limits for 1-mL samples: 9 ng/L for norepinephrine (NE), 8 ng/L for epinephrine (E), and 11 ng/L for dopamine (DA). Precision data resemble those obtained by REA for small-volume samples. Comparison with a liquid chromatography-electrochemical detection (LCEC) technique showed the two methods to be equivalent for NE and E determinations, but DA estimations were lower by REA than by LCEC. PMID- 3342509 TI - Evaluation of a single-color-reading method for determining fructosamine. AB - A commercial kit for determining fructosamine was evaluated. The reference interval (determined from data on 183 nondiabetic subjects) was 1.67 to 2.85 (mean 2.17) mmol/L. Serum and plasma (EDTA- or heparin-anticoagulated) gave equivalent results; plasma treated with fluoride/oxalate gave slightly lower values. The between-run CV was less than 4%. Fructosamine values were similar by the present method and the kinetic method. The standard curve was linear in the range of 1.3 to 8.5 mmol/L. None of several constituents of blood that we tested appreciably interfered. Fructosamine values were increased in some lipemic samples from non-diabetics, and were significantly correlated with glycated hemoglobin as measured by affinity chromatography. This kit evidently is a suitable alternative to the kinetic method for determining fructosamine. PMID- 3342508 TI - A rapid and accurate spectrofluorometric method for quantification and screening of urinary porphyrins. AB - We describe a fluorescence method for screening and quantifying urinary porphyrins. New and effective approaches are used to oxidize prophyrinogens, correct the baseline, and ensure that uroporphyrin (uro) and coproporphyrin (copro) are equally detected, mole for mole. No preliminary purification is required. A 45-microL aliquot of urine is oxidized with 3 mmol/L iodine in 3 mol/L HCl to convert porphyrinogens to porphyrins, and then decolorized with 5 mL of 0.45 mmol/L sodium thiosulfate. An excitation scan is done from 350 nm to 440 nm, monitoring emission at 650 nm. Total porphyrin content is determined at the isosbestic point for uro and copro, and the mole fractions of uro and copro are estimated from the wavelength of the signal maximum. There is no interference from protein, glucose, bilirubin, or hemoglobin in high concentration. The limit of detection is less than 30 nmol/L and linearity is maintained up to 3200 nmol/L. Recoveries and precision are excellent. This is a rapid, sensitive screen for porphyrinuria as well as an accurate and precise quantitative method. We compared the method with existing methods and discuss some shortcomings common to many of them. PMID- 3342510 TI - Microassay for nuclear binding of steroid receptors with use of intact cells from small samples of avian and human tissue. AB - A micro version of a nuclear binding assay to assess the biological activity of receptors for steroid hormones was developed for application to small (needle) biopsies of human tumors for the purpose of predicting responses to steroid therapy. This easier assay requires 10-fold less tissue than the original nuclear binding assay described for progesterone receptors in the avian oviduct, endometrium, and endometrial carcinomas (Spelsberg TC, et al., Endocrinology 1987;121:631). We describe the application of this micro assay to normal avian oviduct and cancers of the human breast, and we demonstrate a tissue specificity and saturation of nuclear binding. The micro assay reliably measured as little as 0.5 mg equivalents of tissue per assay tube. Results for breast tumors determined to be estrogen-receptor-positive by the standard dextran-coated charcoal method were also determined with this nuclear binding assay. As described previously for progesterone receptors in endometrial carcinomas, some receptor-positive breast biopsies displayed negligible capacity for nuclear binding. Therefore, with the present assay we have identified nonfunctional receptors in these biopsies, which may be useful for accurate prediction of patients' responses to therapy with hormones. PMID- 3342511 TI - Adaptations to keep a thyrotropin immunoradiometric assay "supersensitive" with automated pipetting. AB - The sensitivity of the immunoradiometric kit "RIA-gnost hTSH" (Behring) is poorer with a common automated pipetting station than with careful manual pipetting, principally because of tracer contamination of the inner wall of the tube, above the level reached by the wash solution. This can be eliminated by adapting the wash buffer volume so as to fill the entire tube. In this way, one can detect as little thyrotropin as 0.02 milli-int. unit/L, which is better than the 0.03 milli int. unit/L claimed by the manufacturer. Cross-contamination from pipetting can induce overestimation of "suppressed" thyrotropin values. Prolonging the counting time to obtain an optimal counting error is of no practical value in the thyrotropin range where activity is low. PMID- 3342512 TI - Concurrent liquid-chromatographic assay of retinol, alpha-tocopherol, beta carotene, alpha-carotene, lycopene, and beta-cryptoxanthin in plasma, with tocopherol acetate as internal standard. AB - A method is described for simultaneously determining retinol, alpha-tocopherol, beta-carotene, alpha-carotene, lycopene, and beta-cryptoxanthin in 0.25 mL of plasma. Plasma mixed with sodium dodecyl sulfate is deproteinized with ethanol containing tocopherol acetate, then extracted with heptane. The evaporated organic layer is reconstituted with mobile phase (methanol/acetonitrile/chloroform, 47/47/6 by vol) and injected onto a 100 x 4.6 mm 3-micron column of Spherisorb ODS-2 (LKB) at 1.5 mL/min. The alpha- and beta carotenes are well resolved during the 6.5-min run. Retinol is monitored at 325 nm, the tocopherols at 292 nm, and the carotenoids at 450 nm. Extraction of concentrations as great as 135 mumol/L is complete. Intrabatch CVs were 1.7%, 2.3%, 4.1%, 10.4%, 6.4%, and 3.6% for retinol, alpha-tocopherol, beta-carotene, alpha-carotene, lycopene, and beta-cryptoxanthin, respectively. Interbatch CVs for measurements on 30 occasions over 11 weeks were about 10% for all components except alpha-tocopherol (5.3%). Results agree well with those for retinol, alpha tocopherol, and beta-carotene in quality-control samples. PMID- 3342514 TI - Clinical application of serum bilirubin fractionation by simplified liquid chromatography. AB - Serum bilirubin was fractionated by a new reversed-phase "high-performance" liquid-chromatographic (HPLC) procedure, on Micronex RP-30, a polyacryl ester. The five fractions were: delta (delta-bilirubin, B delta), gamma (bilirubin diglucuronide, BDG), beta (bilirubin monoglucuronide, BMG), beta' [(Z,E)- and (or) (E,Z)-bilirubin IX alpha], and alpha [(Z,Z)-bilirubin IX alpha]. We found close correlation with results of the modified HPLC fractionation of Lauff et al. (J Chromatogr 1981;226:391-402), except for the beta' fraction, which was eluted after beta. The Micronex HPLC involves a simple pretreatment of serum samples, in contrast with the complex preparation described by Lauff et al., and is convenient for routine use in the clinical evaluation of hyperbilirubinemia. We could quantify B delta, BDG, BMG, and unconjugated bilirubin even in sera with normal values for total-bilirubin concentrations. Photoderivatives of bilirubin such as the beta' fraction could be separated and quantified by the same procedure, making the method feasible for pediatric research. PMID- 3342513 TI - Improved assay for bismuth in biological samples by atomic absorption spectrophotometry with hydride generation. AB - This simple, rapid, sensitive, reliable, and economical assay for bismuth in plasma, erythrocytes, and urine is based on atomic absorption spectrophotometry with hydride generation. Acid digestion eliminates the problem of foaming, which hitherto has complicated such assay of bismuth in plasma and erythrocytes. The detection limit of the assay has been improved to 0.1 micrograms/L, as compared with a previously documented limit of 2.5 micrograms/L. Average recovery exceeded 95% in all biological fluids. Economy of use derives from elimination of need for electrodeless discharge lamps and atomic absorption grade borohydride. Determination of basal concentrations of bismuth in clinical samples of body fluids gave reference intervals of 0.1-3.5 micrograms/L for plasma, 0.3-4.6 micrograms/L for urine. PMID- 3342515 TI - A dry-reagent strip for quantifying carbamazepine evaluated. AB - We examined a new colorimetric homogeneous immunoassay for carbamazepine based on the apoenzyme reactivation immunoassay system (ARIS) principle. The test, in dry reagent strip format, is to be used with the Ames Seralyzer reflectance photometer. Within-run CVs (n = 20) were 3.0%, 2.7%, and 2.8% at 3.0, 6.1, and 12.1 mg/L; between-run CVs (n = 15, in 15 days) were 4.1%, 2.7%, and 1.9% at 6.0, 9.1, and 12.1 mg/L. Mean analytical recovery was 99.9 (SD 2.3)%. Results by this test (y) for clinical plasma specimens (n = 96) compared very well with those obtained by fluorescence polarization immunoassay (y = 1.01 x - 0.02, r = 0.995) and by liquid chromatography (y = 0.99 x + 0.14, r = 0.990). Bilirubin (45 mg/L), uric acid (145 mg/L), and various anticoagulants at about fourfold the usual concentrations did not interfere. High concentrations of cholesterol (4.9 g/L), triglycerides (3.8 g/L), and hemoglobin (4 g/L) caused slight positive interference. Carbamazepine-10,11-epoxide cross reacted only at greater than or equal to 5 mg/L. The two-point calibration line was validly stored for at least three weeks. Free carbamazepine also can be measured. The test is convenient and rapid (test time 80 s), and thus is particularly useful in all clinical settings where prompt testing is needed. PMID- 3342516 TI - Heterogeneity of serum creatine kinase isoenzyme MM in myocardial infarction: standardization of patterns by use of cord-blood serum. AB - We investigated serum creatine kinase (CK; EC 2.7.3.2) isoenzyme MM in myocardial infarction, using isoelectric focusing in polyacrylamide gels. As many as 14 sub band species were detected, and sequential sampling revealed a progressive anodal shift in their distribution. A nomenclature for sub-band typing is proposed. It denotes the major sub-bands as 1 (pl 6.91), 2 (pl 6.65), and 3 (pl 6.35); which are usually detected in sera of normal CK range. Abnormal sub-bands (associated with increases in the concentrations of CK) are denoted as a (pl 7.55), b (pl 7.35), c (pl 7.25), d (pl 7.05), e (pl 6.85), f (pl 6.72), g (pl 6.50), h (pl 6.40), i (pl 6.28), j (pl 6.20), and k (pl 6.15). Cord-blood sera gave highly reproducible CK-MM patterns characterized by prominent detection of sub-bands 1-3 and faint detection of c, e, f, g, h, i, and j. It is recommended as a standard for CK-MM sub-band typing. PMID- 3342517 TI - Spermidine oxidase activity in serum of normal and schizophrenic subjects. AB - Spermidine oxidase activity in human serum is distributed over a relatively wide range, with a highly significant difference between normal and schizophrenic subjects. The enzyme activity showed no age- or sex-related differences. It is largely inhibited by quinacrine and chloroquine. PMID- 3342518 TI - Intact parathyrin in postmenopausal women. AB - To establish a reference range, we measured intact parathyrin (parathyroid hormone, PTH) in 245 healthy postmenopausal women, ages 42-75 years, with use of the Allegro Intact PTH Kit from Nichols Institute Diagnostics. We also assayed serum from a subset of 120 of the women with kits specific for mid-molecule PTH. The mean intact PTH concentration for the 245 women was 32 ng/L (95% confidence interval 14-60 ng/L). Intact PTH values in these subjects were not normally distributed, although calcium concentrations in the same samples were. There was positive, but not significant (r = 0.12, P = 0.06), correlation between intact PTH and age, and a significant negative correlation between serum calcium and intact PTH that was not observed between calcium and mid-molecule PTH. The improved sensitivity of the intact PTH assay makes it useful in studies of calcium homeostasis in the normal population. PMID- 3342519 TI - Circulating concentrations of immunoreactive peptide 7B2 in certain pathophysiological conditions, and response to oral glucose load. AB - A peptide, 7B2, originally isolated from pituitary, is present in endocrine tumors, with high concentrations in pancreatic islet tumors. Plasma from most of these patients showed very high immunoreactivity to 7B2 (IR-7B2). To assess whether or not there is any alteration in circulating 7B2 concentrations due to age, sex, etc., we measured concentrations in plasma in 96 fasting healthy subjects, ages three months to 91 years; in patients with various other conditions, including pregnancy; and in cord blood. The response of circulating IR-7B2 to oral glucose was also evaluated. We found particularly high IR-7B2 concentrations in cord blood. Postnatally the concentrations were lower and decreased gradually with age to values for adults [15.6 (SE 2.9) pmol/L], increasing again significantly (P less than 0.01) in persons older than 70 years [37.1 (SE 32) pmol/L]. There was no significant sex-related difference in values for plasma. For the pathological conditions studied, we observed significantly supranormal values in patients with chronic renal failure [175.1 (SE 35.9) pmol/L]. Some of the pregnant patients in their third trimester also showed high values. A small but significant increase in plasma IR-7B2 was observed after a glucose load, both in control subjects and diabetics. Perhaps the kidney plays a major role in 7B2 degradation. PMID- 3342520 TI - Immunoassay of low concentrations of albumin in urine by latex particle counting. AB - We describe here a nonisotopic immunoassay, based on particle-counting technology, for the determination of urinary albumin. The assay takes only 35 min and has been fully automated on the IMPACT (Acade Diagnostic Systems, Brussels, Belgium) machine. The system measures albumin within a linear range between 6.25 and 50 mg/L and has a detection limit of 0.4 mg/L. Analytical recoveries at three concentrations ranged between 96% and 102%. Within-run precision ranged from 1.6% to 9.5%. The method was compared with a commercial nephelometric immunoassay system and a correlation coefficient of 0.996 was found for 216 urine samples. No antigen excess affects the shape of the curve in our system, whereas in nephelometry a 3 g/L solution of albumin starts to decrease the dose-response curve. PMID- 3342521 TI - Colorimetry of p-aminohippurate in the presence of sulfamethoxazole. AB - Colorimetric quantification of p-aminohippurate (PAH), which is helpful in assessment of renal function, is subject to interference from sulfa compounds such as sulfamethoxazole. We were unable to measure serum PAH in two patients receiving a trimethoprim-sulfamethoxazole combination because of interference by the latter with the colorimetric estimation. We found that isoamyl acetate removes sulfamethoxazole from the samples without influencing PAH. The extraction is simple, inexpensive, and reproducible. PMID- 3342522 TI - Measuring serum and plasma glucose by the hexokinase method with a reflectance photometer in a high-risk environment. PMID- 3342523 TI - Quantification of urinary albumin and globulin by the sulfosalicylic acid/trichloroacetic acid and DuPont "aca III" analyzer turbidimetric total protein methods. PMID- 3342524 TI - Stability of high-density lipoprotein subfractions in stored plasma. PMID- 3342525 TI - Measurement of blood cholesterol with the Reflotron analyzer evaluated. PMID- 3342526 TI - Automated Ektachem method for measuring sodium in sweat. PMID- 3342527 TI - Determination of ephedrine bioavailability. PMID- 3342528 TI - Evaluation of the coat-a-count radioimmunoassay for phencyclidine. PMID- 3342529 TI - Effect of five different antisera on the immunoturbidimetric determination of urinary albumin. PMID- 3342530 TI - Improved biuret method for determination of fibrinogen. PMID- 3342532 TI - Enzymatic and gas-liquid chromatographic measurement of D-arabinitol compared. PMID- 3342531 TI - Computer program for correction of nonspecific binding in assays of steroid hormone receptors. PMID- 3342534 TI - Evaluation of IMACK-MB, an immunologic extraction assay for the MB isoenzyme of creatine kinase. PMID- 3342533 TI - An additional protein in 2D-PAGE of plasma from the spontaneously hypertensive rat. PMID- 3342535 TI - The cholesterol challenge: from laboratory to clinician. PMID- 3342536 TI - Primary human aspartate aminotransferase reference material. The catalytic activity concentration of AST in RM 8430 as measured by the IFCC reference method for AST in 10 enzyme standardization laboratories. PMID- 3342537 TI - Getting involved in the legal system: choice or chance? AB - The legal system and the laboratory are becoming involved with each other on a daily basis today and the technologist is, willingly or unwillingly, being drawn into this unfamiliar arena. This article will explain some of the manner by which a part of that arena operates, specifically the trial courts. Whether civil or criminal, these courts are governed by rules and methods of operation for the persons in them. In the case of the laboratorian, the role is that of witness, and this article attempts to dispel any fears of that role and teaches how to best prepare for it. PMID- 3342539 TI - Heteroscedasticity and detection of biochemical change. PMID- 3342538 TI - A new analytical system for assessing the protease-antiprotease imbalance in intensive-care medicine. PMID- 3342540 TI - More on the correlation between calcium and total cholesterol in human serum. PMID- 3342541 TI - Protein interference with measurement of ionized calcium. PMID- 3342542 TI - Amdev's "Lytening 2" lithium analyzer evaluated. PMID- 3342543 TI - Sex-related correlation between zinc and calcium in serum. PMID- 3342544 TI - Familial recurrent dislocation of patella with autosomal dominant mode of inheritance. AB - Recurrent dislocation of the patella is considered to be a manifestation of generalized joint laxity. An autosomal dominant mode of inheritance was previously suggested in a few instances; however, male-to-male transmission has not yet been reported. We report a recurrent dislocation of the patella occurring in five generations of one family with male-to-male transmission and without generalized joint laxity. PMID- 3342545 TI - Familial congenital fiber type disproportion (CFTD) with an autosomal recessive inheritance. AB - Two siblings, born to healthy non-consanguineous parents, were found to be affected with congenital progressive severe myopathy. Muscle biopsy revealed fiber type disproportion with no other histological abnormalities, thus confirming the diagnosis of congenital fiber type disproportion and suggesting an autosomal recessive mode of inheritance. This, to our knowledge, is the first reported family in which a strict histological diagnosis of congenital fiber type disproportion has been made and an autosomal recessive mode of inheritance shown. PMID- 3342547 TI - Mild expression of the Pfeiffer syndrome. AB - The acrocephalosyndactylies are a group of conditions with a wide variability of expression. We report a patient with features of the Pfeiffer syndrome (acrocephalosyndactyly type V), initially believed to be a new mutation in her family. Further examination of her mother demonstrated abnormalities of her right thumb which we believe may represent mild expression of the Pfeiffer syndrome. This observation illustrates the variability of phenotypic expression in the Pfeiffer syndrome and underscores the importance of careful investigation of parents and other family members when evaluating individuals with this condition. PMID- 3342546 TI - Hereditary neurocutaneous angiomatous malformations: autosomal dominant inheritance in two families. AB - We present two families in whom the affected members have angiomatous lesions which may be found in both the skin and the central nervous system. Within these families the inheritance is autosomal dominant. PMID- 3342548 TI - Isolated mesomelic shortening of the forearm in father and daughter: a new entity in the group of mesomelic dysplasias. AB - In this report we describe the occurrence of severe mesomelic shortening of the forearms due to hypoplasia of the ulnae with severe radial bowing. In contrast to the mesomelic dysplasias, i.e. Langer type of mesomelic dwarfism, this apparently autosomal dominantly inherited skeletal anomaly occurred as an isolated anomaly without concomitant involvement of shanks or other parts of the skeleton, and did not influence final adult height. PMID- 3342550 TI - ICE syndrome. PMID- 3342549 TI - De novo 3q/7q translocation and associated interstitial 7q35 deletion. AB - In the present report we describe a severely mentally retarded and dysmorphic female child with a de novo 3q/7q reciprocal translocation and loss of band 7q35. This finding supports the hypothesis that the occurrence of mental retardation and/or congenital malformations in de novo autosomal reciprocal translocation may be due to the loss of a small amount of chromatin material during this chromosomal rearrangement. PMID- 3342551 TI - The correlation between the roentgenographic appearance and operative findings at the bone-cement junction of the socket in Charnley low friction arthroplasties. AB - In a series of 200 Charnley low friction arthroplasties revised for various reasons, the preoperative anteroposterior roentgenograms were categorized in terms of demarcation at the bone-cement interface of the socket and compared with the operative findings of movement at the bone-cement junction. All sockets showing no demarcation were found to be fixed soundly. Seven percent of the sockets showing demarcation of the outer one-third only were loose, and when two thirds of the sockets were demarcated, 71% were loose. Ninety-four percent of the sockets with complete demarcation and all sockets that had migrated were found to be loose at revision. There is a definite correlation between roentgenographic demarcation and socket loosening. The more extensive the demarcation, the more likely it is that the socket is loose. Radiographic demarcation of the cemented socket is a prognostic sign for eventual failure. PMID- 3342552 TI - Modular noncemented total hip arthroplasty for congenital dislocation of the hip. Case report and design rationale. AB - The highest rate of failure and the greatest technical difficulty in total hip arthroplasty occurs with congenital dislocation of the hip (CDH). Predisposing factors are failure to secure special femoral components to fit an extremely narrow and straight medullary cavity with space for only a very thin mantle of cement. The acetabulum is usually atrophic, and bone grafts are commonly required to support a small-diameter cup. The young age of the average patient and high levels of activity contribute to cement failure. A new modular cementless prosthesis provides excellent immediate skeletal fixation and pain relief in CDH patients. Five modular components are screwed or press-fit into bone. The modular approach facilitates implantation, reduces inventory, and is adaptable to unforeseen problems. These advantages are ordinarily absent with standard or custom cemented components. Modular components may also permit easier revision. The prosthesis is made of titanium alloy for its superalloy strength, elastic modulus, and bioinertness. By omitting the cement mantle, press-fit is obtained with the largest possible implant. The large size minimizes stem breakage in these young, small bones. Excellent short-term results suggest that modular cementless implants are indicated in some patients with CDH. PMID- 3342554 TI - Histopathologic evaluation in failed Gerard double cup arthroplasty. AB - Fifteen femoral head remnants were removed at revision of an uncemented double cup arthroplasty and were investigated by histological methods. Nine showed resorption of the head, partly due to osteoporosis by stress protection, preexistent pseudocysts, or osteonecrosis. Necrosis was frequently seen in the apicocranial area, and in six cases extended into deeper areas. One failure was attributed to synovitis caused by polyethylene debris. A smooth collagenous membrane developed at both the femoral head and the acetabular interfaces. In some cases metaplasia into cartilage and osteophytes developed at the cup rim. PMID- 3342553 TI - Cefazolin versus cefamandole for prophylaxis during total joint arthroplasty. AB - A prospective, randomized, double-blind comparison of cefazolin versus cefamandole was carried out to evaluate safety and efficacy and to determine bone and serum antibiotic concentrations in patients undergoing total joint arthroplasty. Dosages were 1 g of cefazolin before surgery followed by 500 mg every eight hours for six doses, versus 2 g of cefamandole before surgery followed by 1 g every eight hours for six doses. Intraoperative doses were given during prolonged procedures. No significant adverse drug reactions were clearly attributable to either drug. Among 48 patients receiving cefazolin there was one postoperative wound infection and one distant site infection. Among 49 patients receiving cefamandole, there were two postoperative wound infections and two distant site infections. No deep wound infections occurred in either group during at least 48 months of follow-up study. In hip specimens removed at surgery, the mean antibiotic concentrations were 1.6 +/- 1.4 micrograms/g for cefazolin recipients, compared with 5.7 +/- 5.9 micrograms/g for cefamandole recipients (p less than .001). In knee specimens, the mean antibiotic concentrations were 0.64 +/- 0.57 microgram/g for cefazolin recipients compared to 3.8 +/- 3.4 micrograms/g for cefamandole recipients (p = .004). Cefazolin given at one-half the dose of cefamandole appeared to be equally safe and effective but resulted in lower bone concentrations of antibiotic. PMID- 3342555 TI - Magnetic resonance imaging of soft tissue masses. AB - Twenty-nine soft tissue masses were studied with magnetic resonance imaging (MRI) which proved to be useful in the preoperative evaluation of these lesions. Other imaging modalities employed had significant limitations. Plain films were of little value because of the intrinsically low contrast of soft tissues. Angiography was not necessary unless MRI suggested a vascular lesion or proximity to major blood vessels. Computed tomography (CT) and MRI both readily identified fatty lesions and their relationship to adjacent structures. Some soft tissue tumors could not be delineated from normal muscle with CT, but were easily seen with MRI. MRI is ideally suited for the study of suspected soft tissue tumors because of its excellent soft tissue contrast and its ability to image directly in any plane. Optimum evaluation required imaging in at least two planes with spin echo sequences chosen to bring out both T1 and T2 features. PMID- 3342556 TI - Improving the fit of press-fit hip stems. AB - The implant-bone fit is critical to the longevity of press-fit total hips. Maximum contact on the internal cortical bone surface, especially proximally, produces more normal strain values and reduces micromotion and sinkage. Stem design computer software was developed to design both individualized hip stems that maximize implant-bone contact for a unique anatomy, and average anatomic hip stems in which the mean error of fit is minimized for many patients. Cadaver femurs were used to test the following two hypotheses: (1) Average anatomic stems, designed using the optimal-fit software for an average femoral geometry, improve implant-bone fit when compared with standard stems; and (2) Individualized optimal-fit stems provide an even better fit than average anatomic stems. Results showed that the average anatomical stems fit better than the standard stems. However, the individualized hip stems, designed from individual three-dimensional geometry data, fit the best. PMID- 3342557 TI - Autogeneic cancellous bone grafting following transtrochanteric hip arthroplasty. An attempt to facilitate union of the greater trochanter. AB - A technique involving the use of autogeneic cancellous bone to facilitate union of the greater trochanter following hip arthroplasty via a transtrochanteric approach is presented. This technique has not been previously reported for a large series of patients. Two hundred thirty-five patients were treated with 286 hip arthroplasty procedures via a transtrochanteric approach. All trochanters were advanced 1-2 cm distally and reattached using a three-wire technique. In 111 procedures, cancellous bone taken from the excised femoral head or neck was placed at the inferior aspect of the osteotomy site. In the remaining 175 procedures, no bone grafting was performed. Retrospectively, the incidences of trochanteric nonunion at two-year follow-up evaluation for the nongrafted versus the grafted groups were as follows: 5.7% (10 of 175) versus 2.7% (3 of 111) overall incidence, 4.3% (6 of 139) versus 1.2% (1 of 85) in patients with no previous hip surgery, 8.7% (2 of 23) versus 0% (0 of 10) in patients with previous hip surgery (excluding previous hip arthroplasty), and 15.4% (2 of 13) versus 12.5% (2 of 16) in patients following revision arthroplasty. There was no significant difference in incidence of nonunion between the grafted versus nongrafted groups in any of these categories (chi-square analysis). However, a lower incidence of trochanteric nonunion was found for the patients with autografts in each category, which may indicate a beneficial effect of cancellous bone grafting following trochanteric osteotomy. PMID- 3342558 TI - The role of arthroscopic surgery in the evaluation of acute traumatic hemarthrosis of the knee. AB - Eighty patients presented for evaluation with an acute traumatic hemarthrosis of the knee and negligible instability on clinical examination. All had an examination under general anesthesia followed by arthroscopy. Anatomical lesions were demonstrated in 71 of 80 knees (89%) including anterior cruciate ligament (ACL) disruption in 50 (62%). Twenty-nine of 50 patients (58%) with arthroscopically-demonstrated ACL injuries had associated meniscal tears. Fifteen (19%) demonstrated isolated meniscal tears and nine (11%) osteochondral fractures not detected by conventional roentgenograms. The frequent occurrence of injuries to other joint structures in conjunction with ACL injuries was remarkable. An acute traumatic hemarthrosis of the knee often masks significant lesions. Arthroscopy aids the orthopedic surgeon in determining the full extent of the intraarticular damage. PMID- 3342560 TI - An evaluation of the mechanical failure modalities of a rotating hinge knee prosthesis. AB - The clinical and metallurgical performance of 12 retrieved Noiles total knee prostheses was investigated. Clinical histories and serial roentgenograms were used in conjunction with the American Society for Testing and Materials (ASTM) standard implant retrieval and analysis techniques to assess device performance. All of the devices were removed because of implant loosening with pain, while two devices also had a late infection. The average time in situ for all devices was four years. Roentgenographically, all of the devices showed signs of progressive radiolucencies. Ten (83%) of the devices migrated proximally within the femur. A marked varus drift was observed in eight (67%) of the retrieved prostheses. Hypertrophy of the femoral cortex was observed in eight (67%) of the cases. Seventy-three percent of the polyethylene tibial stems exhibited extensive wear on the anterior and medial aspects of the articulating surface. Extensive wear was also seen on the anterior and extreme posterior aspects in 92% of the polyethylene tibial plateau bearings. This wear was a consequence of the migration of the femoral component leading to buttressing of the plastic components against bone or bone cement. This study indicates serious design flaws in the Noiles knee prosthesis that unless corrected would question the use of the device in either primary or revision knee surgery. PMID- 3342559 TI - Unusual penetrating injury of the knee joint. A case report. AB - Although not commonly recognized, glass may be radiopaque in soft tissue. Its density can be similar to that of bone, and it may be misinterpreted as fracture fragments. The radiodensity of glass is dependent on its varying quantities of iron, silicon, dioxide, aluminum, calcium, magnesium, and sodium salts. The awareness that the radiodensity of glass can be similar to that of human bone on roentgenogram can help the surgeon avoid the pitfall of misdiagnosis. Roentgenograms may be used to detect intraarticular glass and to assist in a localization of glass imbedded in the soft tissue. PMID- 3342561 TI - Tibial torque generation in a flexed weight-bearing stance. AB - Internal and external torque generated about the long axis of the lower extremity was measured in 18 male subjects who were instructed to twist with maximal effort against a fixed footplate containing an instrumented torque cell. Mean torque values ranged from 30 to 71 newton meters (Nm) depending upon the test conditions. Torques recorded during the flexed single-leg stance were 19% to 49% higher than those measured while seated. Values at 45 degrees of knee flexion were 11% to 16% greater than those at 20 degrees. Torques generated while wearing a ski boot were 8% to 11% greater than those recorded in an athletic shoe. When movement of the pelvis and upper torso was allowed, torque values were 17% to 49% higher than those recorded when the hips and shoulders were restrained which allowed only lower leg musculature to act in an isolated fashion. There were no differences between internal versus external generated torques when the hips and torso were restrained. When the hips and shoulders were unrestrained, internal torque was 12% greater than external torque. There were no strong correlations between generated torque and body weight or height. These generated torque values suggest that if ski bindings are set to American Society for Testing and Materials (ASTM) standards for twist-release torque, then upper torso and pelvic movement in conjunction with tensed knee musculature (i.e., a "locked knee") may be necessary to accomplish binding release. Use of the lower leg musculature alone (i.e., ankle twist) may not generate sufficient torque for release. PMID- 3342562 TI - Unicompartmental arthroplasty of the knee with a minimum ten-year follow-up period. AB - The long-term results of 60 Modular Marmor knee unicompartmental arthroplasties with a minimum ten-year follow-up period were reviewed. Valgus, varus, and flexion contracture deformities were corrected. The range of motion was not affected by the arthroplasty, and early postoperative motion prevented the need for manipulation of the knee. Seventy percent of the patients had a satisfactory result based on the Hospital for Special Surgery rating system. The majority of failures were due to technical factors or improper selection of the patient for unicompartmental arthroplasty. PMID- 3342563 TI - Patellar component dissociation in total knee arthroplasty. A report of two cases. AB - Dissociation of the polyethylene from the metal baseplate of the patellar component in total knee arthroplasty (TKA) occurred in two patients. Analysis of intraoperative and postoperative photographs of the specimens indicates that "cold flow" of the polyethylene precedes dissociation from the metal baseplate. The diagnosis can be made on the basis of a pathogonomic metallic crepitus. PMID- 3342565 TI - Bilateral anterior and lateral compartment syndromes in a patient with sickle cell trait. Case report and review of the literature. AB - Bilateral, exercise-induced compartment syndrome occurred in the legs of a 19 year-old black man with sickle trait. Necrosis in the anterior and lateral compartments was so severe that subtotal debridement was ultimately required. Bilateral tibial compartment syndrome is a rare condition. Its occurrence is usually associated with underlying systemic disorders. The authors suggest that sickle cell trait played a role in this patient's dramatic course. PMID- 3342564 TI - Fracture of the porous-coated metal tray of a biologically fixed knee prosthesis. Report of a case. AB - It has been assumed that, when properly implanted, a biologically fixed device is less prone to loosening and probably to fatigue failure as well. This case demonstrates that many of the known risk factors of loosening or fatigue fracture of cemented tibial replacement devices must be considered when using devices designed for biologic fixation. Age, weight, axial alignment, and bone substrate have been identified as probable contributing factors to failure in the case reported here. Manufacturing technique and changes in material properties associated with porous coating should also be carefully tested for factors predisposing the components to fatigue failure. PMID- 3342566 TI - Anterior perineal dislocation of the hip with fracture of the femoral head. A case report. AB - Traumatic anterior perineal hip dislocation with an associated fracture of the femoral head is a rare entity. A 26-year-old man injured in a motorcycle accident was treated by closed reduction of the dislocation within three hours after admission. However, several reports of patients with anterior hip dislocation with associated femoral head fractures were treated nonoperatively and had unfavorable results when treatment failed to achieve anatomical position of the fragments. Consequently, this patient was treated by open reduction and internal fixation of the fractured fragment. Follow-up examination three and one-half years after the operation showed painless functional range of hip motion with only minimal discomfort after prolonged exertion. PMID- 3342567 TI - Sternal Hodgkin's disease. Report of two cases. AB - Hodgkin's disease of the mediastinum presented as a sternal mass in two young adults. The original biopsy materials were incorrectly interpreted as eosinophilic granuloma of bone (histiocytosis X). A delayed diagnosis (15 months) resulted in the death of one patient, whereas the other patient, whose diagnosis was made in one week, had an excellent response to therapy. PMID- 3342568 TI - Displaced malleolar fractures associated with spiral fractures of the tibial shaft. AB - A displaced fracture of the lateral malleolus, of the posterior tibial margin (posterior malleolus), or of both requiring open reduction and internal fixation was observed in association with ipsilateral spiral tibial shaft fracture in five patients. The malleolus fracture components all were managed using AO (ASIF) instrumentation. The tibial shaft fracture was treated nonoperatively in three patients and with interfragmentary screw fixation in two with more severe initial displacement. The bony healing of all fractures was uneventful. These combined injuries amounted to 0.9% of all admitted tibial shaft fractures and 3.9% of those with spiral configuration. An associated displaced malleolar fracture in tibial shaft fractures, sometimes even indiscernible in the anteroposterior view, may be overlooked unless roentgenograms are focused on the ankle joint. Examination of the joints above and below the fracture is of particular importance in clinics advocating functional treatment of tibial shaft fractures. PMID- 3342569 TI - Open tibial fractures treated by anterior half-pin frame fixation. AB - Forty-two open tibial fractures were treated with anterior half-pin frame fixation, weight bearing as tolerated, and early reconstruction of the soft tissue envelope. Thirty fractures were followed to completion of therapy. The infection rate was 7.1%, nonunion rate, 3.0%, and pin tract infection rate, 0.5%. Problems of malunion (23.3%) and of secondary fractures around lag screws (17.6%) may be reduced by early cancellous bone grafting and limited use of minimal internal fixation. PMID- 3342570 TI - Hypertrophic ulnar styloid nonunions. AB - Eleven patients with chronic pain on the ulnar side of the wrist and roentgenographic evidence of a hypertrophic ulnar styloid nonunion were treated with subperiosteal excision of the nonunion fragment. This procedure relieved the localized pain without changing either radiocarpal or distal radioulnar joint stability. PMID- 3342571 TI - The use of freeze-dried allografts in the management of global rotator cuff tears. AB - Massive or global tears of the rotator cuff with loss of tendon substance and retracted cuff remnants pose a challenging surgical and rehabilitation problem. In seven patients, global cuff tears were reconstructed with freeze-dried rotator cuff allografts. Five of the seven patients had other significant debilitating medical problems. Three patients had received four steroid injections, one patient had six injections, and the remaining three patients had two injections in or about the affected shoulder. Five of the seven patients had their pain relieved. Only two patients had significant improvement in shoulder function after anterior acromioplasty and allografts. Freeze-dried rotator cuff allografts do not appear to be of significant value in the surgical management of chronic massive rotator cuff tears. PMID- 3342572 TI - Rupture of the tendon of the long head of the biceps brachii. Surgical versus nonsurgical treatment. AB - Twenty-seven shoulders (in 26 patients) that had surgical repair of a rupture of the long head of the biceps tendon between 1962 and 1981 were evaluated at three to 22 years after injury (mean, 13 years). Thirty similar patients had been treated nonsurgically and were evaluated two to 15 years (mean, 4.6 years) after tendon rupture. Biomechanical testing was performed on ten patients in the surgical group and 13 in the nonsurgical group. Residual arm pain was infrequent in both surgically and nonsurgically treated groups. Residual subjective weakness at the elbow was reported in four of the surgical group and in 20 of the nonsurgical group. Surgically treated patients returned to work later than nonsurgical patients; however, 11 in the nonsurgical group were not able to return to full work capacity, versus only two in the surgical group. On biomechanical testing, the nonsurgical group had lost a mean of 21% of supination strength and 8% of elbow flexion strength but had no weakness in grip, pronation, or elbow extension. The surgical group had lost no strength in any of these testing modes. PMID- 3342573 TI - Fracture of the upper end of the ulna associated with dislocation of the head of the radius in children. AB - Dislocation of the head of the radius associated with fracture of the upper end of the ulna is a common elbow injury in children. The literature on diagnosis, however, is relatively limited. The injury can be misdiagnosed and consequently mismanaged. In the present series of 46 children, the age range was from 2.5 to 12 years. The dislocation of the radial head was lateral in 50% of the cases, posterolateral in 28.2%, anterolateral in 17.4%, and anterior in 4.3%. Thorough clinical and radiological examinations are essential. Simple bending of the upper end of the ulna may help to avoid missing an associated subluxation or dislocation of the radial head. The lower end of the forearm bones should be included in the roentgenographic examination; in 11 out of 46 children (26%) the dislocation of the elbow was associated with a fracture of the lower end of the ipsilateral radius and ulna. Closed reduction is the treatment of choice but if this fails, operative treatment should follow without delay. Posterior interosseous nerve palsy was noted in eight patients (17%), but recovered fully in all of the treated cases. PMID- 3342574 TI - Scapholunate instability following ganglion cyst excision. A case report. AB - Complications following ganglion cyst excision include a 3%-50% recurrence rate, wrist stiffness, infection, neuroma formation, and keloid formation. Scapholunate instability is almost never seen as a complication of ganglion excision. Scapholunate instability occurred following excision of a dorsal ganglion in the wrist of a 38-year-old man. PMID- 3342576 TI - A modified Kidner procedure for symptomatic flat feet. AB - Redirecting the posterior tibial tendon has improved the function of symptomatic flat feet. A modification that appears to improve the final result by increasing the support and fixation of the tendon is reported. PMID- 3342575 TI - Acute carpal tunnel syndrome caused by pigmented villonodular synovitis of the wrist. AB - An 89-year-old woman developed an acute carpal tunnel syndrome secondary to hemarthrosis associated with pigmented villonodular synovitis of the wrist. Pigmented villonodular synovitis is rare in a patient of this age and is an unusual cause of carpal tunnel syndrome. PMID- 3342577 TI - Osteomalacia as a very late manifestation of primary hyperparathyroidism. AB - An 86-year-old woman with a history of treated hyperthyroidism and a 20-year history of untreated primary hyperparathyroidism developed generalized bone pain and a pseudofracture of the midshaft of the left femur. Laboratory examinations revealed elevated serum calcium, alkaline phosphatase, and C-terminal parathyroid hormone levels. Serum inorganic phosphate was below normal and 25-hydroxyvitamin D levels were low-normal. An undecalcified transiliac bone biopsy specimen following tetracycline double labeling revealed osteomalacia and osteitis fibrosa. Following treatment with vitamin D and phosphate, the serum inorganic phosphate level rose to normal. There was a decrease in bone pain, and the pseudofracture healed. However, the serum calcium, alkaline phosphatase, and C terminal parathyroid hormone levels remained elevated. Longstanding primary hyperparathyroidism causes chronic hypophosphatemia and may lead to osteomalacia. Osteomalacia and its consequences may be part of the spectrum of bone disease seen in patients with longstanding primary hyperparathyroidism. PMID- 3342578 TI - Group F Streptococcus. An unusual cause of arthritis. AB - Bacterial arthritis is a serious infection in children occurring either as the result of direct inoculation of organisms into the joint space, of spreading from a contiguous focus of infection, or of hematogenous seeding of the synovium. Although the etiologic agent can be identified in 60% to 70% of cases, joint fluid cultures may remain negative in a substantial number of patients. The most likely etiologic agent depends both on the route of infection and the age of the child. Overall Staphylococcus aureus, Hemophilus influenzae type b and streptococci are the leading causes of bacterial arthritis. Lancefield groups A, B, C, D, and G have all been implicated. However, septic arthritis due to hematogenous seeding with Group F Streptococcus has not been previously reported. A normal 10-month-old boy presented with acute monoarticular arthritis of the knee and had Group F Streptococcus isolated from the blood. Antimicrobial therapy resulted in complete resolution of the arthritis. PMID- 3342580 TI - Benign solitary schwannoma of the foot. A case report and review of the literature. AB - Benign solitary schwannomas of the foot are a rare occurrence; only four cases have been previously reported. A schwannoma associated with the medial plantar nerve present for more than 40 years before the onset of symptoms was diagnosed in a 73-year-old man. Excision of the mass, with preservation of the involved nerve, was possible and successfully relieved symptoms. PMID- 3342579 TI - Postoperative clostridial infection. A case report. AB - The classic fulminating, rapidly progressive, and potentially lethal clostridial myonecrosis (CM), also known as gas gangrene, is a familiar entity. Nevertheless, individual experience with this dreaded disease is extremely rare or nonexistent. Clostridial cellulitis does not involve muscle necrosis and is associated with a lower mortality rate. Although still potentially limb threatening, clostridial cellulitis is a source of considerable morbidity. In a 13-year-old boy the symptoms did not appear until two weeks postoperatively. Definitive treatment was not instituted until five days later. PMID- 3342581 TI - Metastases of carcinoma in the pagetic bone. A report of two cases. AB - Two men, aged 68 and 77 years, had metastases of carcinoma in pagetic bones. These cases were initially diagnosed clinically as Paget's sarcoma. Roentgenograms, scintigrams, and bone puncture biopsy specimens (BPBs) of the right scapula and the sacrum, respectively, showed only Paget's disease. However, an additional BPB obtained with the aid of computed axial tomography (CAT) revealed the presence of metastases of lung carcinoma in the right scapula and of a carcinoma of probable prostatic origin in the pagetic sacrum in the other. The observations testify to the usefulness of CAT-directed BPB when Paget's sarcoma is suspected, especially in cases located in the scapula, pelvis, or spine. PMID- 3342583 TI - Retrospective evaluation of an iodophor-incorporated antimicrobial plastic adhesive wound drape. AB - The incidence of postoperative wound infection following the use of an iodophor incorporated adhesive wound drape with a preliminary one-minute alcohol cleanse was observed in 649 total arthroplasties. The patients were followed for a minimum of one year to detect signs of infection. An infection rate of 0.46% was comparable to the incidence previously observed for conventional methods using an iodine spray as a skin preparation. PMID- 3342582 TI - Intraosseous lipoma of the ilium. A case report. AB - Intraosseous lipoma is the rarest of the benign primary tumors of bone. It occurs most often in the metaphysis of long bones and is usually identified as an incidental roentgenographic finding. A 53-year-old man demonstrated a mass in his buttock and a lytic lesion of his ilium. Preoperative computed axial tomography (CAT) scanning was helpful in establishing its anatomic boundaries and the cellular composition of the mass. The CAT scan demonstrated the tumor extending anteriorly and posteriorly through the ilium and having a uniform soft tissue density with the same attenuation as adipose tissue. The patient was successfully treated with a marginal excision of the tumor. An intraosseous lipoma seems not to have been previously reported to involve the ilium or be associated with significant extension into soft tissue. PMID- 3342584 TI - Paget's disease strikes 3% of the population in the Western World. PMID- 3342585 TI - The prevention of injuries of the brachial plexus secondary to malposition of the patient during surgery. AB - Brachial plexus injuries that occur secondary to malposition of the patient during general anesthesia have been described in the medical literature for nearly a century. However, little can be found in the orthopedic literature. Of the peripheral nerve groups, the brachial plexus may be the most vulnerable to injury from malpositioning. This study presents three such cases of brachial plexus injury and reviews the literature concerning the subject. Pertinent anatomy, etiology, and pathogenesis of injury to the brachial plexus reveal that injury can occur from stretch or compression of nerves and is usually caused by a combination of the two. With awareness of risk factors and the positions which are likely to cause injury to the brachial plexus, careful positioning of the upper extremity can prevent injury and potential disability to the patient. PMID- 3342586 TI - Shoulder hemiarthroplasty at UCLA. AB - Of fifteen patients who had shoulder hemiarthroplasty between 1979 and 1984, eleven had acute four-part proximal humeral fractures, three had avascular necrosis, and one had osteoarthritis. Ten Designed After Natural Anatomy (DANA) and five Neer prostheses were implanted. Four complications occurred. The mean follow-up period was just under three years (range, 13-69 months). Pain relief was excellent but return of function was less consistent. Postoperative active flexion averaged 99 degrees (range, 20 degrees-150 degrees), abduction averaged 99 degrees (range, 50 degrees-150 degrees), and rotation arc averaged 95 degrees (range, 60 degrees-160 degrees). The results were better for patients with avascular necrosis (AVN) than for patients with shoulder trauma. Pain relief was uniformly excellent for patients in both categories, but only AVN patients consistently regained excellent active motion in their shoulders following hemiarthroplasty. PMID- 3342587 TI - Coxa magna following transient synovitis of the hip. AB - In a prospective clinical study of 109 children with transient synovitis of the hip, 32.1% had asymptomatic overgrowth of the femoral head of 2 mm or more (coxa magna) after a follow-up period of one year. Synovial effusion was confirmed with the use of ultrasonography, joint aspiration, or measurement of intraarticular pressure in 93 children and suggested clinically and radiographically only in 16. The most important independent risk factor for later development of coxa magna was radiographic widening of medial joint space with 1 mm or more at admission, which was seen in 42.1% and the presence of which gave a sensitivity of 0.74 and a specificity of 0.73 for coxa magna. At the one-year follow-up examination, the joint space was still wide in 10.1% of the children. The high frequency of coxa magna in these patients and its possible role in the development of degenerative arthritis indicate that transient synovitis of the hip should not be considered a harmless disease until further epidemiologic studies are available. PMID- 3342588 TI - Loosening of the socket in a 35-mm snap-fit prosthesis and the Charnley hip prosthesis. A roentgenographic evaluation of 321 cases operated upon because of osteoarthritis. AB - Migration and lucencies around the acetabular component were evaluated in serial roentgenograms of patients with osteoarthritis treated with total hip arthroplasty (THA); 207 were Charnley and 114 were Brunswik THAs. In this consecutive series of THAs followed for nine to ten years, the loosening rate (corrected for deaths and revisions) was significantly higher (35%-45%) in the Brunswik snap-fit sockets (bearing surface 35 mm in diameter) than in the Charnley sockets (5%-12%). Presumably, mechanical factors, i.e., friction torque and impingement, are responsible for the difference in durability between the two designs. PMID- 3342589 TI - Results of transtrochanteric rotational osteotomy for nontraumatic osteonecrosis of the femoral head. AB - From 1976 to 1985, transtrochanteric rotational osteotomy was applied to 58 hips of nontraumatic necrosis of the femoral head. Of these, 52 hips were available for the present study. The follow-up periods ranged from one to ten years (average, 5.1 years). Satisfactory results were obtained in 69%, as there was no evidence of progressive collapse of the head. Hips that had had no collapse or slight collapse before osteotomy had a significantly better prognosis, compared with those that had marked collapse of the head. The extent of the lesion as depicted on the preoperative lateral roentgenogram also influenced the eventual function. Patient satisfaction was significantly greater when these lesions were less than 70% (31/37), compared with greater than 70% (5/15). PMID- 3342590 TI - Treatment of hip fractures in rheumatoid arthritis. AB - Of 1100 femoral neck fractures observed through an eight-year period, 27 occurred in rheumatoid conditions. The complications and functional results were compared with unselected femoral neck fracture data of nonrheumatoid patients. At two-year follow-up examinations, five of 27 surviving rheumatoid patients had had undisplaced fractures; one of the five developed segmental femoral head collapse. Nineteen of 20 patients with displaced fractures lost position or developed non union or segmental femoral head collapse; 14 required total hip arthroplasty. In the control non-rheumatoid group, six of 27 undisplaced fractures and 34 of 67 displaced fractures developed complications. In displaced fractures, complications occurred more often in rheumatoid patients (p less than 0.0004). Because in rheumatoid patients internal fixation in displaced fractures is associated with an unacceptably high failure rate, primary hip arthroplasty may prove to be the procedure of choice. PMID- 3342591 TI - Total hip acetabular component position affects component loosening rates. AB - Loosening is the most common long-term problem following total hip arthroplasty. Many factors, including patient selection, cement technique, femoral component placement, and prosthesis design reportedly affect the incidence of loosening. Theoretically, the location of the hip center of rotation substantially affects the load on the hip, and superior and lateral hip center location will result in higher loads than medial and inferior placement. Long-term follow-up studies (average, 9.1 years after surgery) using logistical regression analysis demonstrate significantly higher rates of femoral loosening with acetabular components placed in a superior and lateral (i.e., nonanatomic) position, compared with acetabular components placed in a nearly anatomic position. PMID- 3342592 TI - Fractures of the polyethylene bearing insert in Bateman bipolar hip prostheses. AB - Six cases of fractures of the polyethylene bearing insert of Bateman bipolar hip prostheses were observed in three patients at four to eight years after implantation. Three fractured prostheses were salvaged by replacement with new bearing inserts. In three patients, excessive acetabular cartilage wear was the indication for revision to total hip arthroplasty. Although dislocation and component disassembly have been reported as complications of the Bateman and other bipolar prostheses, fractures of the polyethylene bearing insert seems not to have been previously reported. The presumed mechanism of failure is cyclic loading of a femoral cup that is tipped into varus alignment. This concentrates stress on the weakest part of the polyethylene insert--the deep circumferential groove that joins the leaflets to the main body of the insert. Obesity and overuse were associated factors in this rare complication. PMID- 3342593 TI - Total hip arthroplasty in Gaucher's disease. Long-term prognosis. AB - Avascular necrosis of the femoral head is a cause of morbidity in patients with Gaucher's disease. Total hip arthroplasty (THA) is recommended, but there is controversy about the long-term value of this procedure. In eight patients treated with 15 THAs, 11 (73%) have remained fully mobile and asymptomatic up to 14 years following surgery. These long-term follow-up observations are evidence in favor of THA for treatment of hip joint problems associated with Gaucher's disease. PMID- 3342594 TI - Results of core decompression for femoral head osteonecrosis. AB - The progression of femoral head osteonecrosis (FHON) culminates in destruction of the hip joint, a devastating consequence for young people who are predominantly affected. Core decompression, as a means of ameliorating the disease, was evaluated in 45 hips in 33 patients with nontraumatic FHON. The mean clinical and roentgenographic follow-up period was three years (range, 1-7 years). None of the ten Ficat Stage I hips progressed, 11 of 26 Stage II hips progressed, and five of nine Stage III hips progressed to coxarthrosis. In those hips in which there was an association with steroid therapy, there was 50% progression when steroids were continued, compared with 22% progression when steroids had been discontinued. Core decompression is prescribed for Ficat Stage I and II. Patients on continuous post-operative treatment with steroids for associated conditions should be advised of the high risk of progression. PMID- 3342595 TI - Seizures in the neonatal intensive care unit of the 1980s. Types, Etiologies, Timing. AB - A retrospective review was taken of 150 newborns with seizures evaluated at the same medical center and by the same investigator(s) from 1982 to 1987. The aims of the study were to determine in this current population the distribution of clinical seizure types, the distribution of causative etiologies, and the relation of etiology to the timing of onset of the seizures. Seizures were classified as subtle, multifocal clonic, generalized tonic, focal clonic, and myoclonic. Subtle (65% of total) and multifocal clonic seizures (54% of total) were the most common seizure types. Subtle seizures usually occurred in combination with other seizure types. Only one seizure type was related to gestational age, i.e., focal clonic seizures in the term infant. Hypoxic-ischemic encephalopathy (65% of total) was by far the most common etiology in both preterm and term infants. Seizures with hypoxic-ischemic encephalopathy occurred characteristically early in the neonatal period, i.e., 90 percent in the first 2 days of life. Moreover, 80 percent of all seizures in the first 2 days of life were related to hypoxic-ischemic encephalopathy. PMID- 3342596 TI - Determination of the time of closure of the ductus arteriosus in severely ill premature infants. AB - In order to investigate the time of ductal closure in the premature infant, we performed multiple echocardiographic examination in each of 42 premature infants. Twenty eight of these infants had spontaneous closure of the ductus arteriosus (median date of closure--3 days). Twelve required medical or surgical closure of the ductus arteriosus and two died of severe lung disease. There was a significant relationship of decreasing birth weight to prolonged patency of the ductus arteriosus. PMID- 3342597 TI - Late closure of the ductus arteriosus using indomethacin in the preterm infant. AB - Several studies have shown a lack of effect of indomethacin therapy for the closure of a patent ductus arteriosus (PDA) in premature infants over 14 days of postnatal age. In this report we describe two cases in which a hemodynamically significant PDA was closed with indomethacin in preterm infants over 20 days of age. The response to indomethacin may be more related to postconceptual age than to actual postnatal age. We suggest that intravenous indomethacin therapy should be attempted before surgical ligation is performed in those premature infants under 34 weeks postconceptual age who have a hemodynamically significant patent ductus arteriosus. PMID- 3342598 TI - Stool water loss in very-low-birth-weight neonates. AB - Fluid requirements in very-low-birth-weight (VLBW) infants include compensation for renal, insensible (skin and lung), and stool losses and provision for fluid retained for growth. Current estimates of stool water losses in VLBW infants are based on measurements established in term neonates. Therefore, the water content of 24-hour stool collections were determined in 11 healthy VLBW male infants on full enteral feeds and compared to the working norms. The neonates in this study were less than 2 weeks old with a mean +/- SD birth weight and gestational age of 1,311 +/- 112 g and 30.8 +/- 1.5 weeks, respectively. They were receiving only enteral formula feedings of 100 ml/kg/day or more with no parenteral fluid supplementation. The mean +/- SD number of stools and water content of the stools was 2.7 +/- 2.0/day and 7.2 +/- 4.0 ml/kg/day, respectively. There was a significant correlation (r = 0.696, p less than 0.02) between gestational age at birth and number of stools per day, but the correlation between stool water loss per day, gestational age, volume of feedings per day, and birthweight was not significant. Based on this study, 7 ml/kg/day is a reasonable estimate of daily stool water loss in VLBW babies. PMID- 3342599 TI - Persistent neonatal hyperinsulinism. AB - Over a 3-year period, the diagnosis of persistent neonatal hyperinsulinism (PNH) was made in seven infants, from an unselected cohort of 18,726 births, all of Saudi Arabian origin. Thus the incidence of PNH was one in 2,675 births. The high incidence, associated consanguinity, and occurrence in siblings suggest that PNH may be inherited as an autosomal recessive disorder. PMID- 3342600 TI - Flail chest in the newborn. A complication of osteogenesis imperfecta. PMID- 3342601 TI - Medical Research Society communications. 10-11 December 1987, London. Abstracts. PMID- 3342602 TI - Diagnosis of Alzheimer's disease. PMID- 3342603 TI - Diagnosis and management of bleeding disorders. PMID- 3342604 TI - Should we be treating high blood pressure in persons over 65? PMID- 3342605 TI - Magnesium therapy for acute myocardial infarction. AB - Acute myocardial infarction carries a high risk of potentially fatal ventricular arrhythmias during the first 24 hours after the infarct. At this time there is an efflux of K and Mg ions from the injured cells with an associated rise in these cations in the lymphocytes of the peripheral blood. There is a close association between these arrhythmias and the levels of these cations, with a high K level associated with an increased incidence of arrhythmias and a high Mg level being associated with a protective effect. Treatment with a continuous infusion of Mg is highly effective in the prevention of these arrhythmias resulting in a fall in inhospital mortality. PMID- 3342606 TI - Miniature tools offer new hope to facial pain patients. PMID- 3342607 TI - The daily distribution of panic attacks. PMID- 3342609 TI - The use of DSM-III in the United States: a case of not going by the book. PMID- 3342608 TI - Factors associated with depression among primary alcoholics. PMID- 3342610 TI - Relationships between client/counselor congruence and treatment outcome among narcotic addicts. PMID- 3342611 TI - Classification of schizoaffective disorder. PMID- 3342612 TI - Family history of psychiatric disorders in social phobia. PMID- 3342613 TI - Infant feeding: fads and fashions. PMID- 3342614 TI - Incontinence: I'm wet, Mum! PMID- 3342615 TI - Incontinence: a critical eye. PMID- 3342616 TI - An unusual case of disseminated histoplasmosis. PMID- 3342617 TI - Gastric cancer in Connecticut: outlook for improved survival. PMID- 3342618 TI - Radiology corner. Case 1-1988. Thirty-eight year old man with groin pain. PMID- 3342619 TI - Aversion therapy. AMA Council on Scientific Affairs. PMID- 3342620 TI - Fifty hours for the poor. PMID- 3342621 TI - Confidentiality and AIDS: public policy develops. PMID- 3342622 TI - Pulmonary microthrombosis in severe adult respiratory distress syndrome. AB - Pulmonary microvascular occlusive disease has been investigated using balloon occlusive pulmonary angiography in 31 patients with severe adult respiratory distress syndrome (ARDS) of different origins (14 patients with pneumonia, nine with multiple injury, eight with sepsis). Multiple pulmonary artery filling defects (PAFD) were detected in 13 (42%) patients, with a seven (78%) in nine incidence among those with posttraumatic ARDS. The presence of PAFD did not correlate with the severity of the respiratory failure, with the pulmonary hemodynamic alterations (pulmonary hypertension and increased vascular resistance), or with the final outcome (mortality rate was 54% among patients with PAFD and 61% among those with normal angiograms). These findings suggest that widespread pulmonary microthrombosis is a common event in patients with polytrauma and respiratory failure, with an important pathophysiologic role in the onset of posttraumatic ARDS. PMID- 3342623 TI - Acute cardiovascular response to passive leg raising. AB - Cardiac output by thoracic bioimpedance, heart rate, BP, oxygen saturation, and transcutaneous oxygen tension were measured at 1-min intervals in 45 patients before and after passive leg raising (PLR). Mean cardiac index increased only 0.09 +/- 0.02 (SEM) L/min.m2 (p less than .001), mean transcutaneous oxygen tension increased 1.6 +/- 0.6 torr (p less than .01), and mean oxygen saturation decreased 0.5 +/- 0.2% (p less than .01) after PLR. There were no significant changes in heart rate or systolic BP. Seven (16%) patients had increased cardiac index greater than 10% after PLR. PMID- 3342624 TI - Brain hemorrhage associated with methanol poisoning. AB - We recently treated seven patients who were victims of accidental methanol intoxication. Five of the seven patients died within 72 h of hospital admission. The two survivors were discharged from the hospital without visual or neurologic impairment. Hemorrhagic necrosis of the brain was found on CT scan and at autopsy in two patients who died. This complication of methanol intoxication prompted us to review our experience with this poison since 1980. Of 45 methanol intoxication patients treated in our ICU, CT scan was performed in 21, and brain hemorrhage was documented in six, thereby giving an incidence of at least six of 45 or 13.5%. Although hemorrhagic and nonhemorrhagic putamenal necrosis has been described from methanol poisoning previously, we postulate that heparinization during hemodialysis may contribute to brain hemorrhage complicating methanol poisoning and recommend the use of artificial kidneys with albumin-primed biocompatible membranes so that heparin administration during hemodialysis can be minimized. PMID- 3342626 TI - Infrared tympanic thermometer: evaluation of a new clinical thermometer. AB - We have evaluated a new clinical thermometer for accuracy. It determines temperature by measuring infrared radiation given off by a warm object. It was found to be accurate both in vivo and in vitro over the temperature range of 34.0 degrees to 39.5 degrees C. The in vivo assessment was made in patients in the ICU after their return from open heart surgery. The infrared tympanic thermometer tracked the core temperature (as measured by the thermistor tip of the pulmonary artery catheter) closely, with a correlation coefficient of 0.98, and took less than 2 sec to measure. We found this new thermometer to be accurate and, in our opinion, easily usable in the clinical situation. PMID- 3342625 TI - Air embolism and the radial arterial line. AB - A clinical case of apparent air embolism through a radial artery line served as the impetus to conduct a study in primates to investigate the possibility of air embolism from the radial artery into the cerebral circulation. Using 133Xe cerebral scanning, we demonstrated that greater than 2 ml of air in the radial artery would result in retrograde passage of air into the vertebral system and then into the brain. PMID- 3342627 TI - Chest wall acceleration and force measurements in simulated manual and mechanical cardiopulmonary resuscitation. AB - During CPR, the dynamics of the chest compression process play a major role in determining the outcome of the resuscitation effort. To quantify chest wall motion during CPR, a number of important variables must be determined, including maximum downward acceleration and velocity of the chest wall, time during which the wall is held in compression, and maximum depth and rate of chest compression. In this study, miniature accelerometers were used to record chest wall motion during simulated CPR with standard training manikins. One series of CPR tests included force measurements from a three-dimensional force platform placed under the manikin. The results of this investigation showed that American Heart Association (AHA)-certified rescuers are able to produce a consistent pattern of chest wall displacement during a manikin training exercise, and only small differences in displacement recordings are found when comparing one certified rescuer to another. Any given rescuer will usually generate a consistently repeatable acceleration pattern during CPR. However, these cyclical acceleration patterns differ markedly when comparing different certified rescuers. Mechanical CPR with a standard device produced larger peak accelerations than manual CPR. However, the maximum downward velocity was usually higher with manual CPR. In comparison with trained but clinically inexperienced individuals, rescuers with extensive in hospital experience produced relatively larger downward accelerations, longer "hold" times with the chest in compression, and maximum chest displacements that exceeded the current AHA recommendations. Measurements of the force transmitted through the manikin to a force platform clearly indicated the presence of a "hold" phase (if present) and the existence of large force components in the horizontal plane. PMID- 3342628 TI - Contamination reduction during central venous catheterization. AB - This study examined a simple technique for reducing contamination during catheterization of the internal jugular vein. Sixty patients were assigned randomly to receive either a traditional iodophor skin cleansing or an alcohol cleansing, followed by application of an iodophor-impregnated sterile film. In the cleansed with iodophor alone group, 83% of the anesthesiologists' glove tips were contaminated, and 13% of the catheter tips were contaminated. In contrast, in the group in which the sterile film was employed, contamination of gloves and catheters was virtually eliminated. PMID- 3342629 TI - Prognostic score in acute meningococcemia. AB - A prognostic score for children with acute meningococcemia is proposed. We reviewed 176 consecutive patients with acute meningococcemia with ten fatalities admitted to our pediatric ICU in the last 3 yr. The score was obtained from patients in shock, using a stepwise linear discriminant analysis of 18 clinical and laboratory variables on admission. Nine variables showed a significant discriminant power in predicting survival and death: coma, base excess, platelets, glucose, temperature, WBC, sex, purpura, and CSF. The score predicted survival in 100% and death in 91%. The predictive values were significantly better than evaluation by the frequencies of the usual clinical and laboratory variables. PMID- 3342630 TI - Access for drug administration during cardiopulmonary resuscitation. PMID- 3342632 TI - Acute paranasal sinusitis and nasotracheal intubation. PMID- 3342631 TI - Right atrial thrombosis in neonates receiving central venous lines after extracorporeal membrane oxygenation. PMID- 3342633 TI - Norepinephrine therapy in septic shock. PMID- 3342634 TI - Computed tomography as an adjunct to chest x-rays of intensive care unit patients. AB - An analysis of 23 CT scans performed on 20 patients was carried out in an approximate 2-yr period. In 15 patients, CT scans were judged useful by subsequent clinical course when they indicated maintenance or alteration of existing treatment strategies. CT scans in five patients were not helpful. When judged by eventual outcome, the impact of CT scans remains uncertain. The influence of transportation is difficult to assess; it requires experienced team work and is contraindicated in cases where respiratory or circulatory stability might be seriously impaired. PMID- 3342636 TI - Massive doses of midazolam infusion for delirium tremens without respiratory depression. AB - After undergoing replantation and revascularization surgery for a complex hand injury, a 25-yr-old male developed florid delirium tremens. Over a 5-day period, he received 2850 mg of midazolam as a constant infusion of varying rates. The midazolam controlled his severe agitation without respiratory depression and the hand reconstruction survived undamaged. PMID- 3342637 TI - Competent and continuing care of the critically ill. PMID- 3342635 TI - Steady-state dopamine clearance in critically ill infants and children. AB - Little is known about dopamine pharmacokinetics in pediatric patients, especially in critically ill infants and children who often receive treatment with dopamine. Arterial plasma concentrations of dopamine were measured in 27 patients who were hemodynamically stable and received dopamine for at least one hour. The dopamine levels were measured using liquid chromatography with electrochemical detection. Dopamine clearance averaged 96.2 +/- 55.4 ml/kg.min in 13 patients in the neonatal ICU, and 58.8 +/- 51 ml/kg.min in 14 patients in the pediatric ICU. Six patients had renal (BUN greater than 25 mg/dl, or creatinine greater than 1.2 mg/dl) or hepatic (liver enzymes greater than 3 times normal) dysfunction. Dopamine clearance in these patients (25.1 +/- 17.2 ml/kg.min) was substantially lower than in the other patients (p less than .01). Neither postnatal nor gestational age correlated with dopamine clearance. Substantial interindividual variation was observed in steady-state dopamine clearance in critically ill infants and children, and plasma dopamine could not be predicted accurately from the dopamine infusion rate. Because of the more than three-fold prolongation of dopamine clearances in patients with hepatic or renal dysfunction, these patients may be more likely to suffer toxic effects of dopamine at the usual drug infusion rates. PMID- 3342638 TI - Portable chest x-rays in the intensive care unit: importance of erect position. PMID- 3342639 TI - Stopcock-induced bacterial contamination in the infusion system. PMID- 3342640 TI - Closed-tracheal suction system. PMID- 3342641 TI - Metoprolol treatment of multifocal atrial tachycardia. PMID- 3342642 TI - Ventricular tachycardia controlled by cardiac pacing. PMID- 3342643 TI - Control of appetite. PMID- 3342644 TI - Appetite regulation in anorexia nervosa. PMID- 3342645 TI - Metacarpophalangeal relations in 21 Danish patients with achondroplasia. AB - Hand radiographs of 21 Danish patients suffering from achondroplastic chondrodystrophia were obtained to study the metacarpophalangeal relations. Mean pattern profiles based on z-scores were made for males, females, children, and adults. Metacarpal index and relative slenderness for metacarpals and proximal phalanges were calculated. The second to fourth metacarpals and third and fourth proximal phalanges were disproportionately short, and the distal phalanges were disproportionately long. The relation between hand size and height seemed to be the same for the achondroplasts as for normal persons. The metacarpal sign was found in four of the 21 patients. PMID- 3342646 TI - Muscle function in women with rheumatoid arthritis--the influence of glucocorticosteroids. A clinical and morphological investigation. PMID- 3342647 TI - Prenalterol in severe congestive heart failure. II. Long-term oral treatment. Results with comments on the methods for evaluation of drugs in congestive heart failure. AB - Nine patients with severe congestive heart failure were treated with a partial beta-1-agonist prenalterol for 9.6 months on average. Five of the nine patients improved with an increase in NYHA-functional capacity of one class. In four of these patients, the improvement was maintained for 12 months. Upon discontinuation, deterioration occurred only in one case; in the latter, improvement reoccurred on reinstitution of prenalterol treatment. Significant improvement on exercise testing, however, occurred only in two patients. Prediction as to which patients would benefit from oral prenalterol was not possible from the pretreatment haemodynamic variables; similarly, the effect of oral prenalterol treatment could not be predicted from the response to prenalterol given intravenously. A critical review of the methods for evaluation of therapeutic intervention in congestive heart failure concludes the article. PMID- 3342648 TI - Prostaglandin E1 treatment in ductus dependent congenital cardiac malformation. A review of the treatment of 34 neonates. AB - Thirty-four sick neonates with major duct dependent cardiac defects were given short term (1 h-408 h) intravenous infusions of prostaglandin E1 (alprostadil) in doses varying between 0.1 micrograms/kg/min (starting dose) and 0.01 micrograms/kg/min. The aim of the study was to establish an effective and safe regiment that could be initiated after clinical diagnosis of a severe duct dependent cardiac defect, whose clinical course would be adversely affected by ductus closure. After an initial dosage of 0.1 micrograms/kg/min, effective clinical improvement was achieved in 28 infants (82%). In all 28 responders, the effect was maintained at a reduced dosage of 0.05 micrograms/kg/min, and in 21 a low dosage of 0.01 micrograms/kg/min was effective. Side effects, which occurred in 21 infants (62%), were reversible and dose related, and no serious side effects were noted at a dosage of less than 0.05 micrograms/kg/min. A starting dose of 0.05 micrograms/kg/min with subsequent reduction is recommended, but in case of institution of treatment before transfer to a pediatric cardiac centre a lower starting dose of 0.01 micrograms/kg/min may be preferred. PMID- 3342649 TI - Neurological sequelae and fatality as prognostic measures in 875 cases of bacterial meningitis. AB - Based on a review of medical records, we have analysed the outcome after bacterial meningitis among 875 patients admitted during the period 1966-1976. The outcome was evaluated not only by fatality during admission or within 4 weeks after discharge, but also by neurological sequelae at the time of discharge. These two types of outcome were determined and compared in subgroups of patients categorised according to a number of features of prognostic significance. This has allowed us to quantify the clinical conditions and features with regard to the severity of the prognosis. In most subgroups of patients, the frequencies of fatality and sequelae followed the same patterns: High frequencies were associated with pneumococcal meningitis, rare bacterial aetiologies, increasing age, affected consciousness on admission, pneumonia on admission, convulsions during admission, and respiratory problems during admission. For some prognostic features, a correlation could be established with high sequelae rates, but not with high fatality rates. This was the case with increased duration of disease symptoms before admission, with alcoholism and with previous head trauma. Thus, this correlation revealed the importance of early hospitalisation. We find that the analysis of sequelae not only supports, but also adds important prognostic information to the results obtained by an analysis of fatality itself in this large retrospective clinical study. PMID- 3342650 TI - Radical cystectomy for residual of recurrent tumour after definitive radiotherapy (salvage cystectomy). AB - The results of salvage cystectomy for persistent or recurrent tumour following definite radiotherapy in 47 patients are reviewed. The calculated five-year survival rate was 25% for all stages, with a significantly better survival for the low pathological stages. Operative mortality was 12.8%. It was concluded that salvage cystectomy is a suitable supplement in the treatment of bladder cancer in spite of the considerable operative mortality and complication rate. PMID- 3342651 TI - Is asthma mortality increasing? PMID- 3342652 TI - Thin-section CT and the solitary pulmonary nodule. PMID- 3342653 TI - Clinical value of assessment of acute reversibility of airways obstruction in patients with COPD. PMID- 3342654 TI - Obliterative bronchiolitis in children. AB - Clinical, radiologic and histologic features of obliterative bronchiolitis (OB) in children were reviewed to define features helpful in early recognition. All autopsies (n = 2,897), lung biopsies (n = 244), and medical records of children followed at St. Christopher's Hospital for Children (SCHC) between 1960 and 1985 were screened. Nineteen cases of OB were confirmed using radiologic and histologic criteria. Twelve patients were diagnosed during life, and ten survived. Seven were diagnosed post mortem. OB should be considered when persistent respiratory signs and symptoms follow acute pneumonia, aspiration is known or suspected, areas of hyperlucency are seen on chest radiograph, or respiratory failure with overaeration is unresponsive to therapy. Diagnostic studies include ventilation-perfusion scan, bronchography and lung biopsy. Sequelae include dyspnea on exertion, obstructive lung disease, bronchiectasis, persistent atelectasis, and hyperlucent lung syndrome. Recognition and supportive treatment during the acute and chronic phases may improve the functional status of these patients. PMID- 3342655 TI - The effects of hypoxemia on cardiac output. A dose-response curve. AB - To establish a dose-response curve for the effects of isocapnic hypoxemia on cardiac output (CO), we studied 20 healthy men, aged 20 to 34 years, using a tight-fitting face mask and an isocapnic partial rebreathing system (a modified anesthesia machine). We blended oxygen and hypoxic gas to achieve arterial oxygen saturations (SaO2) of 80, 85, and 90 percent; subjects also breathed 100 percent oxygen and room air (RA). Target SaO2 and end-tidal carbon dioxide were continuously monitored using an ear oximeter and CO2 gas analyzer. Subjects experienced the five SaO2 measurements in random order. CO was measured noninvasively at approximately two-minute intervals, using continuous-wave Doppler echocardiography. Mean cardiac output increased with increasing hypoxemia from 6.84 L/min at FIo2 1.0 to 8.44 L/min at SaO2 80 percent (p less than 0.0005); the increase was entirely due to increased heart rate. We concluded that cardiac output increases significantly in a dose-response manner in response to acute isocapnic hypoxemia in normal persons. PMID- 3342657 TI - Ventricular fibrillation complicating acute myocardial infarction. Two distinct clinical and electrocardiographic features. AB - Two distinct electrocardiographic patterns of ventricular fibrillation (VF) complicating acute myocardial infarction (AMI) were observed in 34 patients during the first 24 hours from initial symptoms. Type 1 (seven patients) was characterized by fast disorganized ventricular activity, small voltage, and no clear identifiable QRS complexes (fine VF). Type 2 (27 patients) was defined as multiform QRS configuration (greater than 300/min) with marked changes in the amplitude (polymorphous VF). Type 1 rhythm was seen mostly during the hyperacute ischemic phase, probably associated with total coronary vessel occlusion; type 2 was observed when Q waves were already present in the electrocardiogram. PMID- 3342656 TI - Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction. AB - Traditionally, patients with acute airflow obstruction are treated with bronchodilator aerosols delivered by continuous flow nebulizers. While bronchodilator administration with the metered dose inhaler (MDI) and reservoir or spacer attachment is as effective as administration with the nebulizer in most settings, the former has not been widely accepted for treatment of acute airway obstruction in the emergency room. We compared the efficacy of the continuous flow nebulizer to that of the MDI with InspirEase (reservoir spacer) in 75 patients (45 men and 30 women), ages 18-73 (chi 44 years) who presented to the emergency room with acute asthma and COPD. Subjects in each group (22 COPD and 53 asthma) were randomly assigned to treatment with three puffs of metaproterenol (0.65 mg/puff) via the MDI with InspirEase plus nebulizer with placebo, or placebo MDI with InspirEase plus nebulizer with 15 mg metaproterenol in double blind fashion. Either treatment was given three times at 30 min intervals. The FEV1 and dyspnea scores according to the Borg scale were measured at baseline, 30 min after the first treatment, and 30 min after the third. There was no significant outcome difference between the two treatments in either diagnostic group. There also was no significant outcome difference for patients with baseline FEV1 less than 0.9L. Serum theophylline levels, the need for concomitant therapy with corticosteroids, or additional emergency room therapy after the study, hospitalizations and treatment side effects did not differ between treatment groups. We conclude that there is no demonstrable advantage of a continuous flow nebulizer over an MDI with InspirEase for the treatment of acute airflow obstruction. PMID- 3342659 TI - Prehospital autotransfusion in life-threatening hemothorax. AB - Eighteen patients with life-threatening traumatic hemothorax received prehospital autotransfusion using a simple new device. During transfer to the hospital, they received 3.9 +/- 0.5 L of colloid fluid and 4.1 +/- 0.6 L of autotransfused blood, without anticoagulation. Hemorrhagic blood was not coagulable, had a hematocrit of 20 +/- 4 percent, few platelets, and low fibrinogen levels. Five patients died from irreversible hemorrhagic shock. Thirteen patients were alive upon admission to the hospital, underwent emergency surgery, and were discharged alive. During autotransfusion, hematocrit decreased from 24 +/- 3 to 19 +/- 3 percent, and systolic arterial pressure increased from 78 +/- 11 to 88 +/- 12 mm Hg. Upon admission to the hospital, platelet count was 90,800 +/- 21,400/cu mm, prothrombin time 48 +/- 3 percent, partial thromboplastin time 197 +/- 18 percent, plasma free hemoglobin levels 21 +/- 7 mg/100 ml, and serum potassium levels 3.6 +/- 0.5 mmol/L. No serious complication could be related to autotransfusion considered to be crucial to patients' survival. The preliminary results of this study suggest that autotransfusion might be developed in the prehospital setting since it appears simple and safe, and represents the only hope of survival for patients with life-threatening hemothorax. PMID- 3342658 TI - Bias and precision of pulse oximeters and arterial oximeters. AB - We evaluated measurements of oxygen saturation from four noninvasive pulse oximeters, and two conventional arterial oximeters. Simultaneous measurements were obtained on each instrument on three different occasions in five healthy subjects breathing gas with an FIO2 of 1.00, 0.50, 0.21, 0.17, 0.15, 0.13 and 0.11. Mean bias relative to the sum of oxy-, carboxy-, and methemoglobins ranged from -0.4 to -2.6 percent for the pulse oximeters and +1.8 to -4.2 percent for the conventional oximeters. Two pulse oximeters performed well at all saturations down to 65 percent, while the others showed either increasing or decreasing bias below 80 percent saturation. Precision was approximately 2 percent for all instruments except one conventional oximeter with a precision of 0.7 percent. In the clinically relevant range, the performance of the noninvasive pulse oximeters was similar to conventional oximeters using arterial samples. PMID- 3342660 TI - Penetration of aminoglycosides in uninfected pleural exudates and in pleural empyemas. AB - The concentrations of gentamicin, netilmicin, and amikacin were determined after one single intravenous injection in uninfected pleural fluid after thoracotomy and in purulent pleural empyemas. The mean peak concentrations in the pleural fluid after the injection of gentamicin (1.5 mg/kg), netilmicin (2.0 mg/kg), and amikacin (7.5 mg/kg) were 2.9 +/- 0.3 mg/L, 3.7 +/- 0.8 mg/L, and 11.0 +/- 3.1 mg/L, respectively. The pleural penetration of the drugs was very high (from 80.0 to 99.1 percent). By contrast, gentamicin and netilmicin were not detectable in empyema pus; in this exudate the mean peak level of amikacin was 5.7 +/- 2.2 mg/L, with the penetration of this drug being 31.0 percent. The concentrations of parenterally administered aminoglycosides are substantially lower in empyema pus than in sterile pleural fluid. The possibility of poor pleural penetration of some aminoglycosides, as well as the presence of local conditions in pleural empyema unfavorable to the bioactivity of these drugs, must be kept in mind when treating pleural infections. PMID- 3342661 TI - Optimum anesthesia with intrapleural lidocaine during chemical pleurodesis with tetracycline. AB - Chemical pleurodesis with tetracycline is frequently complicated by pleuritic chest pain. The most promising approach to control pain is to optimize the use of intrapleural lidocaine. While administering amounts of intrapleural lidocaine larger than commonly reported, we attempted to determine a safe and more effective dose, by using a subjective and objective assessment of pain, by measuring serum concentrations of lidocaine, and by observing patients for possible toxic effects of lidocaine. Chemical pleurodesis with tetracycline was performed on ten patients receiving an intrapleural dose of 200 mg of lidocaine (group 1) and on ten patients receiving a 250-mg dose (group 2). A significantly greater number of patients in group 2 were free of pain following pleurodesis (7/10 vs 1/10; p = 0.006). Of the 80 serum lidocaine levels obtained, only one value (6.1 micrograms/ml), in an asymptomatic patient in group 1, exceeded the therapeutic range (1.5 micrograms/ml to 5.5 micrograms/ml). One patient in group 2 experienced transient numbness of the right hand, a possible side effect of lidocaine. We conclude that to achieve optimum anesthesia during chemical pleurodesis with tetracycline, it is necessary to use doses of intrapleural lidocaine large than previously reported. Until the feasibility of a further escalation is demonstrated, 250 mg should be considered the standard dose. PMID- 3342662 TI - Determination of total respiratory resistance in health and disease by added external resistance. AB - Previous studies have indicated that total respiratory resistance (Rrs) can be measured by addition of an external resistor. In an earlier study, the apparatus used to accomplish this included a multiperforated steel plate. In this study, we sought to improve the device. Details of this are given in this article. With this device, resistance was found to be reproducible over five consecutive days, and was sensitive to the increase in airway resistance induced by head and neck flexion. We also report on a comparison between this method and a commercially available device that works on the "interruptor" principle. There was no significant difference in either mean or variance of resistance between the two methods. The instrumentation required for the newly designed method is minimal, and its operation is simple. Furthermore, the measurement can be performed without invasive procedures during tidal breathing. PMID- 3342663 TI - Lidocaine concentrations in bronchoscopic specimens. AB - We measured lidocaine concentrations in bronchoscopic specimens and found that bronchoalveolar lavage (BAL) concentrations (16 +/- 7 micrograms/ml) were lower than those in bronchial washings (967 +/- 379 micrograms/ml [p less than 0.001]). Lidocaine concentrations in bronchial washings obtained "early" (991 +/- 505 micrograms/ml) compared with "late" (943 +/- 580 micrograms/ml) in the procedure did not differ (p = NS). High lidocaine concentrations sufficient to inhibit growth in culture of mycobacterial and fungal pathogens (greater than 5,000 micrograms/ml) occurred in one early and two late bronchial washings but no BAL specimens. No correlation between lidocaine dose and measured concentrations was noted in any specimen category; however, highest bronchial washing concentrations occurred with the use of greater than 250 mg of lidocaine. We conclude that BAL specimens are suitable for culturing pathogens that may be inhibited by lidocaine. Furthermore, collecting bronchial washings late in the procedure or limiting the lidocaine dosage do not reliably decrease measured lidocaine concentrations. PMID- 3342665 TI - Flexible fiberoptic endoscopy for airway problems in a pediatric intensive care unit. AB - We used flexible fiberoptic endoscopy to evaluate 87 patients with potential problems of the airway in a pediatric intensive care unit. Four different-sized bronchoscopes were used to perform 61 diagnostic laryngoscopic procedures, 35 diagnostic bronchoscopic procedures, and eight therapeutic bronchoscopic procedures. Diagnostic information was obtained in 91 of 96 procedures. Of the eight therapeutic procedures, seven were considered successful. Morbidity was minimal, and there was no death. Flexible fiberoptic endoscopy proved useful as a bedside technique for critically ill pediatric patients in whom evaluation of the airway in the operating room under general anesthesia would have been difficult. PMID- 3342664 TI - Nontuberculous mycobacterial lung disease. Substantiation of a less aggressive approach. AB - A nonsurgical, less aggressive, less toxic chemotherapeutic protocol for the management of nontuberculous mycobacterial (NTB) pulmonary infections has been uniformly applied to patients in our institution between 1972 and 1985. Forty three nonimmunocompromised patients with active lung disease caused by Mycobacterium avium-intracellulare (MAI) (n = 26), M kansasii (n = 16), and M xenopi (n = 1) were identified retrospectively. Eighteen MAI patients were treated with three or four antituberculosis agents resulting in sputum conversion and clinical improvement in 12 (67 percent). Additionally, 11 out of 16 (69 percent) patients completing therapy or still undergoing therapy for persistent MAI disease, achieved sputum conversion and clinical improvement after prolonged therapy (3.6 +/- 0.5 years [SEM]). When M kansasii was identified as the etiologic agent, all patients were treated with four or fewer antituberculosis agents and 14 out of 16 patients (88 percent) achieved sputum conversion and clinical improvement throughout the follow-up period. We conclude that the use of three or four chemotherapeutic agents in the treatment of NTM lung disease provides an excellent probability of successful outcome even in MAI infections. PMID- 3342666 TI - Veracity of disability claimants' self-reports of current smoking status. Comparison of carboxyhemoglobin levels from disability claimant and reference population. AB - Carboxyhemoglobin level (%COHB) obtained during pulmonary function testing was used as a measure of recent tobacco smoking among persons claiming to be nonsmokers and ex-smokers. Asbestos disability applicants and reference routine clinical patients had similar mean %COHB (2.09 +/- 1.34 and 1.99 +/- 0.88, respectively) and proportions with abnormally elevated %COHB (35 and 46 percent, respectively, had %COHB greater than 2 percent). However, comparisons of persons claiming to be ex-smokers and nonsmokers showed that the ex-smokers had higher mean %COHB (p less than 0.001 by analysis of variance) and proportions with elevated %COHB. This study suggests that disability applicants and routine clinical patients do not differ in veracity of self-stated smoking information, but many persons claiming to be ex-smokers are actually not. PMID- 3342667 TI - Usefulness of tissue polypeptide antigen in staging, monitoring, and prognosis of lung cancer. AB - A study of tissue polypeptide antigen (TPA) serum levels was conducted in patients with various cell types of bronchial carcinoma. A total of 548 assays (226 pretreatment) were evaluated. In all, the sensitivity of the test at diagnosis was 61 percent. It varied considerably in relation to the extent and site of disease. Individual pretreatment values of TPA correlated significantly with the stage of disease. Similarly, posttreatment TPA values related to disease evolution. In small cell carcinoma, eight of the 29 meaningful changes in follow up levels of TPA preceded clinical recognition of disease status variations. Raised pretreatment values of TPA were significantly associated with a shortened survival. These results indicate that TPA may contribute to staging, monitoring, and prognosis of lung cancer. PMID- 3342668 TI - Glucocorticoid receptors in bronchoalveolar lavage fluid in sarcoidosis. A preliminary report. AB - Glucocorticoid receptor (GR) content was measured in bronchoalveolar lavage fluid (BALF) cells of 20 untreated patients with sarcoidosis. A significantly higher (p less than 0.001) lymphocyte count and GR content of BALF cells was noted in patients with sarcoidosis as compared to normal volunteers. The GR content correlated positively with lymphocytes (%) (r = 0.6; p less than 0.01) and was significantly higher (p less than 0.001) in patients who showed roentgenographic improvement, physiologic improvement, and improvement in both parameters compared to those who did not show improvement. Above findings suggest that the GR content of BALF cells is increased in sarcoidosis and a major contribution to this may be made by the lymphocytes. PMID- 3342669 TI - Evaluation of clinical methods for rating dyspnea. AB - To evaluate available clinical methods (self ratings and questionnaire) for rating dyspnea, we (1) compared scores from the recently developed baseline dyspnea index (BDI) with the Medical Research Council (MRC) scale and the oxygen cost diagram (OCD) in 153 patients with various respiratory diseases who sought medical care for shortness of breath; and (2) evaluated the relationships between dyspnea scores and standard measures of physiologic lung function in the same patients. The dyspnea scores were all significantly correlated (r = 0.48 to 0.70; p less than 0.001). Agreement between two observers or with repeated use was satisfactory with all three clinical rating methods. The BDI showed the highest correlations with physiologic measurements. Dyspnea scores were most highly related to spirometric values (r = 0.78; p less than 0.001) for patients with asthma, maximal respiratory pressures (r = 0.34 and 0.35; p less than 0.001) for patients with chronic obstructive pulmonary disease, and PImax (r = 0.51; p = 0.01) and FVC (r = 0.44; p = 0.03) for those with interstitial lung disease. These results show that: (1) the BDI, MRC scale, and OCD provide significantly related measures of dyspnea; (2) the clinical ratings of dyspnea correlate significantly with physiologic parameters of lung function; and (3) breathlessness may be related to the pathophysiology of the specific respiratory disease. The clinical rating of dyspnea may provide quantitative information complementary to measurements of lung function. PMID- 3342670 TI - Alternans of the ST segment in variant angina. Incidence, time course and relation to ventricular arrhythmias during ambulatory electrocardiographic recording. AB - The ST alternans was recorded during at least one ischemic attack with ST elevation in nine of 65 patients with variant angina. The magnitude and duration of ST elevation during ischemic attacks were significantly greater in patients with than in those without ST alternans. It always appeared during the occlusion phase and disappeared during the reperfusion phase of ischemic attacks. In patients with episodic ST alternans, the ischemic attacks showed a greater ST elevation and a longer duration in the presence of ST alternans than in its absence. The incidence of occlusion phase ventricular arrhythmias was greater in patients with than in those without ST alternans; the incidence of reperfusion phase ventricular arrhythmias was similar in the two groups. The ST alternans always preceded the onset of occlusion phase arrhythmias. Thus, in variant angina, ST alternans represents an index of the severity of ischemia and a precursor of ventricular arrhythmias. PMID- 3342671 TI - Solitary pulmonary nodules. CT-bronchoscopic correlation. AB - The possible contribution of computed tomography (CT) in the management of patients with solitary pulmonary nodules (SPNs) or masses was reviewed retrospectively in 65 patients undergoing fiberoptic bronchoscopy (FOB). Nodules were evaluated by size, location, surface contour, and the presence in cross section of a bronchus leading to or contained within the nodule or mass, a "positive bronchus sign." Thirty-five lesions were associated with a positive bronchus sign; 21 of 35 (60 percent) were diagnosed endoscopically, (p = .027); of 30 cases with a negative bronchus sign, only ten (30 percent) had a diagnosis made by FOB (p = .034). It is concluded that CT may be of use in the routine evaluation of pulmonary nodules, prior to bronchoscopy, especially in cases for which histologic evaluation is essential, especially to determine the presence or absence of a CT bronchus sign. PMID- 3342672 TI - Efficacy of intra-aortic balloon pumping for failing Fontan circulation. AB - The Fontan circulation occasionally cannot be sustained by currently available medical treatment. In these circumstances, mechanical assistance to the Fontan circulation should be considered. We have experienced three cases where Fontan circulation was assisted by intra-aortic balloon pumping (IABP). The hemodynamic improvement and weaning from IABP were successfully achieved in all cases. One patient survived the serious postoperative course with the aid of IAPB, and two patients died following multiorgan failure, though the circulation had eventually been re-established. By studying the postoperative hemodynamics assisted by IABP, it is concluded that IABP is a reasonable, efficacious strategy to support and to re-establish the failing Fontan circulation, though the changes in hemodynamic variables will not immediately coincide with IABP application. PMID- 3342673 TI - Lambert-Eaton myasthenic syndrome involving the diaphragm. AB - Inspiratory muscle function was assessed in a patient with the Lambert-Eaton myasthenic syndrome that developed in association with a bronchogenic carcinoma. Repetitive maximal inspiratory pressure measurements and the electromyographic response to phrenic nerve stimulation established involvement of the inspiratory muscles in general and the diaphragm specifically in this condition. PMID- 3342674 TI - Death from bronchial asthma. AB - There is now incontrovertible evidence that there is a progressive and strikingly increased mortality from bronchial asthma in the US. The increase is more dramatic in the older age groups, but younger age groups are not spared. The exact cause or causes of this increased mortality are not known, and it is even possible (although not likely) that the increase is artifactual. This increased death rate is in sharp contrast to the general medical perception that major advances in the management of bronchial asthma have occurred. Perhaps they have, but if so, more patients are dying during this period of advances than were dying before. The most prudent course would be to assume that the excess deaths are iatrogenic in origin and to act accordingly. Even if this assumption is flawed, acting on it would improve the management of patients with bronchial asthma. If it is true that the major purpose of risk-benefit analysis is to improve patient outcome rather than merely analyze risk-benefit balance, then a series of proposals can be generated to grapple with this problem in bronchial asthma. PMID- 3342675 TI - Intermittent atelectasis of the left lung. PMID- 3342676 TI - Angulated fluoroscopy with light localizer in percutaneous lung biopsy. PMID- 3342677 TI - Silent aortic dissection with hemopericardium. Diagnosis by computerized tomography. AB - An asymptomatic woman was evaluated because of a chest x-ray examination suggesting an aortic aneurysm. CT scan revealed proximal aortic dissection, which had apparently leaked into the pericardium. Increased use of CT scanning is expanding our knowledge of the clinical spectrum of aortic dissection. PMID- 3342678 TI - Thoracic hemangiomatosis masquerading as interstitial lung disease. AB - Pulmonary capillary hemangiomatosis is an extremely rare condition, first described by Wagenvoort. In this condition, sheets of thin-walled blood vessels infiltrate the lung parenchyma, bronchioles, and pleura. Three previous cases have been described in the literature. We describe a fourth. It probably represents a congenital abnormality. PMID- 3342679 TI - Acute cardiac tamponade due to cardiac actinomycosis. AB - Cardiac actinomycosis occurs in less than 2 percent of the patients with infections due to Actinomyces israelii. We describe the findings in a patient with acute cardiac tamponade who survived through pericardial drainage and aggressive medical therapy. Although uncommon, this disorder is important to recognize because it is curable with current medical and surgical therapy. PMID- 3342680 TI - Pregnancy in a woman with severe pulmonary fibrosis secondary to hard metal disease. AB - The effect of interstitial pulmonary fibrosis on pregnancy is unclear. We present the findings in a 31-year-old woman with severe pulmonary fibrosis (vital capacity, 37 percent of predicted) secondary to hard metal disease who went through a successful term pregnancy. The patient was a grinder of tungsten carbide drill bits who developed pneumonitis and subsequent fibrosis. Her therapy required steroids and cyclophosphamide for stabilization of her pulmonary function prior to her pregnancy. At six months' gestation, right heart catheterization showed normal cardiac output and pulmonary arterial and wedge pressures. Stage 2 exercise study demonstrated a maximum oxygen consumption of 1.17 L/min (53 percent of predicted). The patient was able to exercise to a maximum workload of 300 kpm/min (32 percent of predicted). She became hypoxemic (arterial oxygen pressure, 54 mm Hg) at 150 kpm/min. Her pregnancy concluded with an uncomplicated normal vaginal delivery requiring only supplemental oxygen and spinal anesthesia. Review of the few similar cases suggests that a woman can have a successful pregnancy despite severe pulmonary dysfunction. PMID- 3342682 TI - Postpneumonectomy dysrhythmias. PMID- 3342681 TI - Epithelioid hemangioendothelioma. A rare tumor with variable prognosis presenting as a pleural effusion. AB - The chest x-ray film a 22-year-old man showed a large right-sided pleural effusion that was grossly hemorrhagic when aspirated. A computerized tomographic scan showed a complex mass with cystic components contiguous with the diaphragm. On thoracotomy the mass was found to be arising from the diaphragm and had the consistency of an organizing hematoma. Pathologic studies showed the mass to be an epithelioid hemangioendothelioma. This rare tumor has never been reported previously as arising from the diaphragm. It has a variable prognosis, but surgery remains the treatment of choice. In this report, we review the clinical and pathologic characteristics of this unusual tumor, as well as the distinctive roentgenographic findings with which it presented. PMID- 3342684 TI - Pneumothorax in substance abuse. PMID- 3342683 TI - Atelectasis caused by acute hyperosmolality. PMID- 3342685 TI - Necrotizing soft tissue infections and adjunctive hyperbaric oxygen. PMID- 3342686 TI - Differential diagnosis of pulmonary nodule. PMID- 3342687 TI - Massive extracardiac thallium accumulation in pulmonary carcinoma. PMID- 3342688 TI - Pathogenesis of pulmonary hypertension in the rat model. PMID- 3342689 TI - The regulation of synthesis of platelet-activating factor by endothelial cells. PMID- 3342690 TI - Acute and chronic fetal pulmonary hypertension alter pulmonary vasoreactivity. PMID- 3342692 TI - Endothelial cell xanthine oxidase-derived toxic oxygen metabolites contribute to acute lung injury from neutrophil elastase. PMID- 3342691 TI - Vascular remodeling in neonatal pulmonary hypertension. Role of the smooth muscle cell. AB - We suggest that hypoxia-induced pulmonary hypertension in the newborn calf is an attractive model for studying the mechanisms underlying alterations in extracellular matrix accumulation which occur in pulmonary vascular disease. Our data support a model (Fig 7) in which the SMC, perhaps as a result of hypoxic and/or pressure-induced vessel wall injury, becomes phenotypically altered. This phenotypically altered SMC generates a factor, termed smooth muscle derived extracellular matrix factor (SMEF), and possibly other factors. SMEF, in turn, stimulates or induces elastin and collagen synthesis in fibroblasts and endothelial cells. SMEF, or an associated activity derived from phenotypically altered smooth muscle cells, also induces elastin receptor expression on the cell surface and affects the chemotactic responsiveness of vascular cells. Thus, the SMC may be able to affect both the secretory and responsive properties of cell types in the vascular wall. The SMC may be critical in the vascular remodeling in pulmonary hypertension. The possible autocrine or paracrine alteration of cellular phenotypes by smooth muscle-derived mediators provides an important new direction for future research into molecular and cellular mechanisms of connective tissue regulation in diseased vessels. PMID- 3342693 TI - Alterations in pulmonary vascular responsiveness following hyperoxic injury to the lung. PMID- 3342694 TI - Reperfusion injury occurs in the lung by free radical mechanisms. PMID- 3342695 TI - Heparin prevents pulmonary artery remodeling in postobstructive pulmonary arteriopathy in dogs. PMID- 3342696 TI - Hypoxia and the pulmonary microvasculature. Physiology and pathophysiology. PMID- 3342697 TI - Effects of hypoxia and hypercarbia on cultured endothelial cells. PMID- 3342698 TI - Subacute hypoxic exposure increases lung transvascular protein escape in rats. PMID- 3342699 TI - Characterization of pulmonary smooth muscle cell growth activity from hypoxic pulmonary endothelial cells. PMID- 3342700 TI - Growth factors and diacylglycerol stimulate pulmonary vascular endothelial ornithine decarboxylase activity. PMID- 3342702 TI - Cause of increased right and left atrial pressures in patients with obstructed airflow disease. PMID- 3342701 TI - Pulmonary vascular endothelial cells modulate stretch-induced DNA and connective tissue synthesis in rat pulmonary artery segments. PMID- 3342703 TI - 30th Annual Aspen Lung Conference: Pulmonary circulation and pulmonary hypertension. PMID- 3342704 TI - Capillary recruitment in the pulmonary microcirculation. PMID- 3342705 TI - Pulmonary vascular smooth muscle contractility. Effect of free radicals. PMID- 3342706 TI - Increased wedge pressure facilitates decreased lung vascular resistance during upright exercise. PMID- 3342707 TI - Child-mother attachment and the self in six-year-olds. AB - Bowlby has proposed that child-parent attachment is important in the child's representation of self. In this study, the child's representation of self was examined in connection with child-mother attachment in a sample of 52 white, middle-class 6-year-olds. Children were seen in 2 play sessions, 1 month apart. Quality of attachment was assessed in each session based on the child's behavior on reunion following a laboratory separation of approximately 1 hour, using a system devised by Main and Cassidy. Aggregated attachment ratings and classifications were assigned based on the child's behavior in both reunions. Assessments of the self consisted of (a) assessment of the self within the relationship with the attachment figure (an incomplete doll stories procedure), (b) assessment of the child's perceptions of how an unspecified "other" views him or her (a puppet interview), (c) direct assessment of global self-esteem independent of the attachment relationship (the subscale of global self-esteem from Harter's Perceived Competence Scale for Children), (d) a second direct assessment of global self-esteem (an interview with the child), and (e) assessment of feelings of competence and acceptance in specific domains that may be precursors of self-esteem (Harter's Scale of Perceived Competence and Social Acceptance for Young Children). Significant, albeit modest, connections between attachment and the self were established; furthermore, specific patterns of self perceptions were related to particular patterns of attachment. PMID- 3342709 TI - Nonmaternal care in the first year of life and the security of infant-parent attachment. AB - Evidence from 2 longitudinal studies of infant and family development was combined and examined in order to determine if experience of extensive nonmaternal care in the first year is associated with heightened risk of insecure infant-mother attachment and, in the case of sons, insecure infant-father attachment. Analysis of data obtained during Strange Situation assessments conducted when infants were 12 and 13 months of age revealed that infants exposed to 20 or more hours of care per week displayed more avoidance of mother on reunion and were more likely to be classified as insecurely attached to her than infants with less than 20 hours of care per week. Sons whose mothers were employed on a full-time basis (greater than 35 hours per week) were more likely to be classified as insecure in their attachments to their fathers than all other boys, and, as a result, sons with 20 or more hours of nonmaternal care per week were more likely to be insecurely attached to both parents and less likely to be securely attached to both parents than other boys. A secondary analysis of infants with extensive care experience who did and did not develop insecure attachment relationships with their mothers highlights several conditions under which the risk of insecurity is elevated or reduced. Both sets of findings are considered in terms of other research and the context in which infant day-care is currently experienced in the United States. PMID- 3342708 TI - Attachment in late adolescence: working models, affect regulation, and representations of self and others. AB - The purpose of this study was to examine the coherence of attachment organization during late adolescence. In a sample of 53 first-year college students, 3 kinds of working models of attachment were assessed with the Adult Attachment Interview: Dismissing of Attachment, Secure, and Preoccupied with Attachment. Affect regulation was evaluated with peer Q-sort ratings of Ego-Resiliency, Ego Undercontrol, Hostility, and Anxiety, and representations of self and others were assessed with self-report measures of distress, perceived competence, and social support. The Secure group was rated as more ego-resilient, less anxious, and less hostile by peers and reported little distress and high levels of social support. The Dismissing group was rated low on ego-resilience and higher on hostility by peers and reported more distant relationships in terms of more loneliness and low levels of social support from family. The Preoccupied group was viewed as less ego-resilient and more anxious by peers and reported high levels of personal distress, while viewing their family as more supportive than the Dismissing group. These findings are interpreted in terms of different styles of affect regulation and representational bias associated with particular working models of attachment. PMID- 3342710 TI - Maternal social networks and mother-infant interactions in full-term and very low birthweight, preterm infants. AB - The relation between maternal social networks and mother-infant interactions at 6 months of age was examined in 34 mother-preterm and 20 mother-full-term dyads. All preterm infants were of very low birthweight and experienced medical complications. Mothers were interviewed regarding their social networks; ratings of maternal behaviors were derived from videotaped mother-infant interactions. There were few between-group differences in mean levels of network variables; however, the association between network structure and maternal sensitivity differed in the 2 groups. A larger number of ties between the mother's family of origin and the mother's friends related to higher maternal sensitivity in full terms but to lower maternal sensitivity in preterms. The birth of a full-term infant is typically a positive event around which a tightly knit network can coalesce to support the mother. It is less clear that the birth of a preterm infant is a positive event, leaving network members unsure of their roles and how to respond. Under the latter circumstances, fewer ties among network members may decrease the likelihood of ambiguous or stressful communications. PMID- 3342711 TI - Neurobehavioral and neurophysiological assessment of healthy and "at-risk" full term infants. AB - The Neurological and Adaptive Capacity Score (NACS) and the auditory brainstem response (ABR) are measures that, respectively, provide neurobehavioral and neurophysiological information regarding the status of the central nervous system (CNS) in the neonatal period. We evaluated these measures as indices of CNS functioning in 15 neonates born at risk for neurological sequelae and 15 healthy controls. Significant group differences were observed on the NACS. The ABR failed to distinguish the groups, but abnormal responses were obtained from 1 severely asphyxiated infant. Measures used to define ABR abnormality were also correlated among risk infants. We concluded that the NACS is sensitive to mild but diffuse disturbances, whereas the ABR appears to reflect insults to the brainstem structures that are susceptible to damage from anoxia. Utilization of both tests provides more complete information regarding CNS integrity in neonates. PMID- 3342712 TI - Intermodal learning in infancy: learning on the basis of two kinds of invariant relations in audible and visible events. AB - In this research, the development of intermodal perception in infancy was examined by using a new method, the intermodal learning method. 3-month-old infants were given the opportunity to learn a relation between 2 single film and soundtrack pairs through a 2-min familiarization period under 1 of 4 conditions. Films of naturalistic events were accompanied by a soundtrack that was (1) appropriate to the composition of the object and synchronous with its motions, (2) appropriate and nonsynchronous, (3) inappropriate and synchronous, or (4) inappropriate and nonsynchronous. A group of control subjects was familiarized with irrelevant films and soundtracks. Then all subjects were tested in a 2 choice intermodal preference test to determine under which familiarization conditions intermodal learning had occurred. Results indicated that only subjects who had been familiarized with appropriate and synchronous film and soundtrack pairs showed evidence of intermodal learning as compared with the performance of control subjects. Intermodal learning occurred on the basis of 2 kinds of invariant audio-visual relations, temporal synchrony, and temporal microstructure specifying the composition of the object. Intermodal learning did not occur through association on the basis of co-occurrence, nor did it occur when any incongruent audio-visual structure was present. These findings support an invariant-detection view of the development of intermodal perception. PMID- 3342713 TI - A critical test of infant pattern preference models. AB - Models of infant visual preferences with predictions based on the physical attributes of visual patterns were evaluated using pairs of schematic faces and abstract patterns that were identical except for contrast reversals. Preferences at 6 weeks were entirely consistent with the predictions of these models. However, at 12 weeks the preferences for facelike images were in clear violation of the predictions of these models. These results represent the first unambiguous demonstration of a face preference in young human infants. The results also allow rejection of all current stimulus-based models of visual preference and suggest that a fundamental change in the determinants of visual preference occurs between 6 and 12 weeks postnatally. PMID- 3342714 TI - Infant imitation and memory: nine-month-olds in immediate and deferred tests. AB - The ability of 9-month-old infants to imitate simple actions with novel objects was investigated. Both immediate and deferred imitation were tested, the latter by interposing a 24-hour delay between the stimulus-presentation and response periods. The results provide evidence for both immediate and deferred imitation; moreover, imitative responding was not significantly dampened by the 24-hour delay. The findings demonstrate that there exists some underlying capacity for deferring imitation of certain acts well under 1 year of age, and thus that this ability does not develop in a stagelike step function at about 18-24 months as commonly predicted. These findings also show that imitation in early infancy can span wide enough delays to be of potential service in social development; actions on novel objects that are observed one day can be stored by the child and repeated the next day. The study of deferred imitation provides a largely untapped method for investigating the nature and development of recall memory in the preverbal child. PMID- 3342715 TI - Specific intellectual deficits in children with early onset diabetes mellitus. AB - 27 children with early onset (less than 4 years) diabetes (EOD), 24 with late onset (greater than 4.0 years) diabetes (LOD), and 30 sibling controls were compared in their performance on tests of intellectual functioning and school achievement. The results indicated that children with EOD, particularly girls, scored lower than the other groups of diabetic children and siblings on tests of visuospatial but not verbal ability. Many of the children with EOD were also having difficulty at school, and a number were currently receiving special education. Diabetic children with earlier onset had more hypoglycemic convulsions than those with later onset. Regression analyses revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. PMID- 3342716 TI - Children's understanding of representational change and its relation to the understanding of false belief and the appearance-reality distinction. AB - This research concerns the development of children's understanding of representational change and its relation to other cognitive developments. Children were shown deceptive objects, and the true nature of the objects was then revealed. Children were then asked what they thought the object was when they first saw it, testing their understanding of representational change; what another child would think the object was, testing their understanding of false belief; and what the object looked like and really was, testing their understanding of the appearance-reality distinction. Most 3-year-olds answered the representational change question incorrectly. Most 5-year-olds did not make this error. Children's performance on the representational change question was poorer than their performance on the false-belief question. There were correlations between performance on all 3 tasks. Apparently children begin to be able to consider alternative representations of the same object at about age 4. PMID- 3342717 TI - Conflicting goals in self-evaluative information seeking: developmental and ability level analyses. AB - Developmental changes in the resolution of conflicting goals involved in self evaluation were examined in children entering second, fourth, and sixth grades representing high, medium, and low ability levels in arithmetic. Children completed a series of arithmetic tasks and were given an opportunity to evaluate themselves in terms of social comparison or autonomous comparison. As expected, overall, high-ability children engaged in the most self-evaluative information seeking, whereas low-ability children engaged in the least information seeking. Moreover, with increasing age, high-ability children were more likely to engage in autonomous comparison, whereas low- and medium-ability children maintained an interest in social comparison. In addition, greater interest in social comparison, particularly among older children, was associated with relative uncertainty about one's own ability but perceptions of ability as constant in others. The results are discussed in terms of strategies for balancing self assessment with self-enhancement needs and the impact of such strategies for task mastery. PMID- 3342718 TI - Factors that influence induction of gastroesophageal reflux in normal human subjects. AB - Findings from recent studies indicate that transient relaxation of the lower esophageal sphincter (LES) is an important contributory mechanism to spontaneous episodes of gastroesophageal reflux (GER) in normal subjects as well as in patients with reflux esophagitis. Our study aim was to evaluate the interrelationship between reduction of LES pressure and elevation of intraabdominal pressure in the induction of GER in healthy subjects. Seven volunteers were studied supine after gastric loading with 0.1 N HCl. A pH probe recorded acid GER. Leg raising (LR) or abdominal compression (AC) were used as stress maneuvers to increase intraabdominal pressure, either alone or in combination with stimuli that concurrently lowered LES pressure, namely multiple rapid swallows (RS) or intraesophageal balloon distention (BD). Each individual stimulus and stimulus combination was tested three times, giving a total of 24 test maneuvers per subject. The test maneuvers elicited 2-12 GERs in each subject. The GER incidence for single maneuvers was: AC, 0%; LR, 0%; RS, 19%; and BD, 24%. LR in combination with RS or BD did not increase the incidence of GER above that induced by RS or BD alone. In contrast, AC concurrent with RS and BD increased the incidence of GER to 52% and 81%, respectively. For all test conditions, a prerequisite for the occurrence of GER was a fall in LES pressure to a minimal value of 3 mm Hg or less. GER never occurred when LES pressure was greater than or equal to 4 mm Hg, even during intervals of increased intraabdominal pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342719 TI - Plasma CCK levels in patients with pancreatic insufficiency. AB - After stimulation with a Lundh test meal, plasma concentrations of cholecystokinin (CCK) and pancreatic polypeptide (PP) and output of pancreatic enzymes were measured in 33 patients with exocrine pancreatic insufficiency and 26 healthy subjects. Patients with impairment of pancreatic function were subdivided into those with moderate and severe insufficiency. Plasma CCK and PP were measured by radioimmunoassay. Fasting plasma CCK in patients with pancreatic insufficiency (5.8 +/- 1.1 pmol/liter) did not differ significantly from controls (4.2 +/- 0.6 pmol/liter). After endogenous stimulation with a Lundh meal, plasma CCK increased in both groups without significant differences over 2 hr. Basal and stimulated plasma levels of pancreatic polypeptide (PP) were markedly decreased only in patients with severe pancreatic insufficiency. Our results demonstrate that basal and meal-stimulated CCK levels in patients with pancreatic insufficiency do not differ from controls. Furthermore the extent of functional impairment of the exocrine pancreas did not influence basal and postprandial CCK release. PMID- 3342720 TI - Intragastric bile does not perturb gastric emptying of liquids in humans. AB - Gastric stasis and duodenogastric reflux have each been implicated in the pathogenesis of various upper gastrointestinal disorders. However, the relationship between intragastric bile and gastric emptying has not been explored. In each of nine healthy volunteers (seven men and two women, ages 22-47 years), gastric emptying of 300 ml 10% dextrose labeled with [99mTc]DTPA was measured twice using gamma camera imaging. During one study, 20 min after ingestion of the test meal, 525 mg of freeze-dried, sterilized human T-tube bile dissolved in 20 ml water was introduced into the stomach via a previously sited fine-bore nasogastric tube. Intragastric bile salt concentrations were calculated to be within the range 1.7-2.9 mM. In control studies, 20 ml of water alone was similarly introduced. Emptying at 20 min was comparable for both groups of studies (38 +/- 3% vs 39 +/- 4%; mean values +/- SEM). For each individual study, emptying from 20 to 60 min was well represented by a single exponential function (r = 0.81-0.99). Half-emptying times for curves fitted over this period were similar in the two groups (bile: T1/2 = 18.8 +/- 2.6 min; control T1/2 = 18.8 +/- 1.9 min). These results indicate that intragastric bile, in concentrations similar to those found in patients with gastric ulcer, has no effect on gastric emptying of dextrose in normal subjects. PMID- 3342721 TI - Prediction of lactose malabsorption in referral patients. AB - Two hundred forty-two patients referred for various gastrointestinal complaints were evaluated for clinical parameters that would predict findings of lactose malabsorption. Breath hydrogen and blood glucose lactose tests were performed after ingestion of 50 g lactose. Presenting complaints, duration of symptoms, and patient demographics such as age, sex, and ethnic heritage were not different between lactose malabsorbers and absorbers as defined by the breath hydrogen lactose test. Food-related symptoms in general and after specific foods such as milk, ice cream, cheese, and yogurt were also similar between groups. Prior to testing, 30% of malabsorbers (N = 161) and 36% of absorbers (N = 81) reported lactose-related symptoms (P = NS). The blood glucose response to lactose was abnormal in 60% of malabsorbers and 15% of absorbers. This study confirmed our impression that it is difficult to predict lactose absorption status by clinical parameters. The majority of our lactose malabsorber patients were unaware of lactose-associated symptoms. Furthermore, symptom assessment, demographics, food history, and blood glucose testing did not predict abnormal hydrogen responses to lactose. PMID- 3342722 TI - Impact of age, sex, race, and functional complaints on hydrogen (H2) production. AB - In order to evaluate factors that may influence H2 generation, the effects of age, sex, race, and functional complaints on breath H2 were studied in 62 subjects. These included 34 young hospital employees, 17 healthy ambulatory elderly subjects, and 11 patients with functional bowel disease. The ability to produce H2 was defined by an increase in breath H2 to greater than 20 parts per million within 4 hr of ingesting 10 g of the nonabsorbable sugar lactulose. Overall, 21% of subjects were nonproducers, and the incidence of nonproduction did not vary among the groups. The elderly subjects had significantly greater breath H2 concentrations than the younger subjects at 150 minutes (P less than 0.05). Sex, race, and functional complaints did not influence H2 production. These findings indicate that patient's age and potential inability to make H2 need to be considered in the routine interpretation of H2 breath tests. PMID- 3342723 TI - Lymphoid follicular proctitis. A condition different from ulcerative proctitis? AB - A heterogeneous group is formed by patients presenting with clinical features suggestive of inflammatory bowel disease limited to the rectum and whose rectal biopsies show lymphoid follicular hyperplasia of the mucosa. All these cases are traditionally considered as one variant of chronic ulcerative colitis, so-called ulcerative proctitis. Twenty such cases were critically assessed on clinical, endoscopic, and histologic grounds, as well as on response to treatment and follow-up data. While 11 patients showed clinicopathologic features consistent with typical chronic ulcerative colitis, the other nine patients appeared to form a different group, for which the term "lymphoid follicular proctitis" seemed justified. Lymphoid follicular proctitis was, overall, characterized by rectal bleeding, a congested and granular mucosa without ulceration, abnormal and coalescing hyperplastic lymphoid follicles without acute inflammation, and failure to respond to local steroid therapy. The nature of lymphoid follicular proctitis is uncertain at present but seems unrelated to chronic ulcerative colitis. PMID- 3342724 TI - Sequential endoscopy and biopsy of intact rat stomach. A new simple technique. AB - This paper describes the technique of sequential endoscopy and biopsy of the intact rat stomach. It is recommended that this procedure be performed on fasted animals with access to water only, when a mortality of only 4% can be achieved. PMID- 3342725 TI - Cysteamine-induced inhibition of mucosal and pancreatic alkaline secretion in rat duodenum. AB - To determine the effect of cysteamine on the alkaline secretion by the duodenal epithelium, pancreas, and Brunner's glands in relation to the pathogenesis of duodenal ulceration, the alkaline secretion by various types of duodenal loops was comparatively studied. The results obtained were as follows: (1) Cysteamine significantly reduced both mucosal and pancreatobiliary alkaline secretion in the proximal duodenum of rats. (2) The ratio of contribution of pancreatobiliary alkaline secretion to total neutralization of acid in the proximal duodenum was 55.9% under continuous perfusion. (3) There was no significant difference between the amounts of alkali per unit volume of the proximal and distal duodenal loops. (4) The alkaline substance secreted by the proximal duodenal mucosa was confirmed to be the bicarbonate. From these findings, it has been concluded that the impairment of bicarbonate secretion by the mucosal epithelium of proximal duodenum, not by Brunner's glands, plays a causative role in cysteamine-induced duodenal ulceration. PMID- 3342727 TI - Reflux from ileum to colon in the dog. Role of external ligamentous attachments. AB - In four dogs we quantified the role of external ("coloileal") ligaments in preventing coloileal reflux. All animals were tested under control conditions, and then two had all external ligamentous attachments between ileum and colon divided; the other pair underwent a sham operation. Coloileal reflux was quantified scintigraphically at colonic pressures of 20, 40, and 60 mm Hg, and ileal motility was recorded concurrently. During control experiments and after sham operations, no dogs showed coloileal reflux at colonic pressures of 20 and 40 mm Hg. At a colonic pressure of 60 mm Hg, two control experiments and one in a dog after sham operation resulted in reflux of 9%, 4%, and 8% of counts, respectively. In contrast, both test dogs (after division of the ligaments) refluxed 30-70% of colonic content in all of four experiments at pressure below 20 mm Hg. In control dogs and in those with a continent ileocolonic junction, ileal motility consisted of scattered clusters of phasic contractions. In dogs with coloileal reflux, these clusters occurred with a similar frequency, but they lasted longer (P less than 0.005). Four weeks later, ileal motility indices in control dogs were significantly less (P less than 0.02) than in animals with divided coloileal ligaments. These observations establish an experimental model for coloileal reflux, support the hypothesis that external ligamentous attachments help maintain continence at the ileocolonic junction, and imply that coloileal reflux changes the motor pattern of the terminal ileum. PMID- 3342726 TI - Effect of cisplatin on myoelectric activity of the stomach and small intestine in dogs. AB - The effect of cisplatin on interdigestive myoelectric activity (IDMA) of the gastric antrum, duodenum and jejunum, plasma concentration of motilin, and animal behavior was studied in seven conscious dogs with gastric cannulas and platinum electrodes implanted on the serosal surface of antrum and upper small intestine. Cisplatin given intravenously in a dose of 2 mg/kg resulted in complete interruption of IDMA and produced predominantly phase II-like activity, lasting as long as 24 hr. Six of the seven dogs exhibited retropropagation of spike bursts from the jejunum to the antrum which was accompanied by emesis. Retropropagation of spike bursts did not occur in one dog who did not exhibit emesis. In addition, abnormal spike bursts occurred frequently, including simultaneously occurring spike bursts in both duodenum and jejunum and nonpropagating short spike bursts in isolated segments of the upper small intestine. As phase III of IDMA disappeared, plasma motilin concentrations remained comparable to those in phase II of normal IDMA but without the cyclic increases. These studies indicate that cisplatin interrupts the regular cycle of IDMA as well as the plasma motilin cycle and produces retropropagation of spike bursts and abnormal spike bursts. These changes in both motility and plasma motilin levels may play a part in the mechanism of emesis induced by cisplatin in dogs. PMID- 3342729 TI - Propranolol and HBsAg-positive cirrhosis. PMID- 3342728 TI - Submassive hepatic necrosis associated with the use of progabide: a GABA receptor agonist. AB - Progabide, a recently introduced gamma-aminobutyric acid mimetic, is currently undergoing clinical evaluation for a variety of convulsive disorders. We describe a patient in whom severe hepatic failure developed after four weeks of Progabide therapy. The patient's course was marked by encephalopathy, jaundice, hypoglycemia, markedly elevated serum aminotransferase levels, and prolongation of the prothrombin time. Liver biopsy showed extensive hepatocellular necrosis. The patient recovered slowly after discontinuation of the drug. The finding of eosinophilia and increased serum IgE suggests an immunologically mediated mechanism for the Progabide-induced hepatic injury. Alternatively, the lipophilic moiety of Progabide may interact with hepatocyte cell membrane lipids leading to toxic injury. We conclude that Progabide may occasionally cause severe hepatic injury. PMID- 3342730 TI - Intestinal permeability in the elderly. PMID- 3342731 TI - Pregnancy and the liver. PMID- 3342732 TI - Comparison of early renal dysfunction in type I and type II diabetes: differing associations with blood pressure and glycaemic control. AB - This study has investigated the relationship of glycaemic control, blood pressure and proteinuria to early renal dysfunction in a cohort of 50 type I and 65 type II diabetics, with renal function ranging from normal to mildly impaired (serum creatinine less than 0.2 mM). Repeated measurements were made over a mean interval of 7 years and mean data from each subject were analysed by stepwise multiple linear regression. This enabled associations to be determined independently of the confounding influence of age and duration of disease. In type I diabetics, mean creatinine clearance was inversely related to systolic blood pressure (P less than 0.001), glycosylated haemoglobin (P less than 0.05), fasting plasma glucose (P less than 0.05) and to the renal clearance of albumin (P less than 0.001), transferrin (P less than 0.01) and IgG (P less than 0.05). By contrast, in type II diabetics, none of these associations were significant. No significant relationships were found with the rate of decline of creatinine clearance in either type of diabetic. Further studies will be needed to determine whether the changes in blood pressure and glycaemic control precede or follow the development of renal disease. However, these findings raise the possibility of a difference in the pathogenesis of renal disease in type I and type II diabetes. PMID- 3342734 TI - Casual blood glucose levels and prevalence of undiscovered diabetes mellitus in Lagos Metropolis Nigerians. AB - A diabetic screening exercise involving 1627 subjects (1050 males and 577 females) was carried out in the Lagos Metropolis of Nigeria. Casual capillary blood glucose and/or urine glucose were tested for by means of dipsticks. The prevalence rates of undetected diabetes in the males and females were respectively 1.5% and 1.9%. Mean (+/- SD) casual blood glucose levels were higher in the females (82.8 (+/- 19.1) mg/100 ml) than in the males (75.9 (+/- 16.2) mg/100 ml). The prevalence of renal glycosuria was 1.3% in the males and 0.2% in the females. The prevalence of diabetes mellitus in the Lagos Metropolis appears high but similar to that in many other countries. The ambient blood glucose in the non-hospitalized subjects also seems to be not significantly different from values reported in other places. PMID- 3342733 TI - Glucose tolerance in Polynesia: association with obesity and island of residence. AB - Data on five Polynesian populations, obtained by standardized population surveys conducted during the years 1978-1980, were examined for associations between glucose tolerance and both obesity and island of residence. In both sexes, after allowing for the influence of age and obesity, there was a significant difference in glucose tolerance between the three populations considered, subjectively, to be the less traditional and the two considered as retaining a more traditional lifestyle. Regression models predicting diabetic status were weaker than those using glucose tolerance as the dependent variable, probably due to the small number of diabetic subjects in the samples. As all subjects were of Polynesian ancestry, and the results could not be explained by knowledge of ancestral affiliations between the five populations, environmental, rather than genetic factors may have been the determinants of the observed differences in glucose tolerance. This finding highlights the need for a more sophisticated approach to the study of the association between socio-cultural modernization and chronic disease in the Pacific. PMID- 3342735 TI - The association between symptomatic sensory neuropathy and body stature in diabetic patients. AB - In the diabetic patient the clinical manifestations of peripheral neuropathy occur more commonly in the distributions of longer neurons. Utilizing height as a proxy variable, we have examined whether neuron length is also a determinant for the occurrence of peripheral neuropathy among diabetic patients. In studies performed at two sites (Sheffield and Miami) the heights of diabetic patients with symptomatic peripheral neuropathy were compared with those of non neuropathic diabetic patients. At each site the neuropathic patients were significantly taller (P = 0.02 for Sheffield and P = 0.01 for Miami). These data were not biased by age or race. Body stature (as a proxy for neuron length) appears to be a constitutional risk factor for diabetic peripheral neuropathy. PMID- 3342736 TI - An epidemiologic approach to the study of retinopathy: the Pittsburgh diabetic morbidity and retinopathy studies. AB - Diabetic retinopathy was studied in two cohorts of insulin-dependent diabetics (IDDs) from the Children's Hospital of Pittsburgh. The first cohort (n = 696) consisted of IDDs of long duration. Severe retinopathy was self-reported in 70% of this cohort by 30 years duration of diabetes. Associations between severe retinopathy, hypertension and smoking were observed. In order to examine the relationship between metabolic control and early diabetic retinopathy, a second cohort of adolescent IDDs (n = 58) were referred for standardized fluorescein angiography. Sixty-four percent had early retinopathy. None had proliferative changes. Significant differences in individual mean whole blood glycosylated hemoglobin (GHb), averaged over 3 years before angiography, were consistently seen between those with and without early retinopathy. Also, the number of microaneurysms was positively correlated with individual mean GHb. Before the advent of GHb testing, those IDDs who later had retinopathy were more likely to have experienced at least one hospitalization for diabetic ketoacidosis. These observations provide strong support that poor metabolic control preceded the development of diabetic retinopathy. Results are consistent with the hypothesis that improvement of metabolic control early in the course of IDDM may prevent or delay the development of the early changes of diabetic retinopathy. PMID- 3342737 TI - [Immunolymphoscintigraphy. A new procedure for noninvasive lymph node staging illustrated by the example of breast cancer]. AB - In the course of a prospective study 43 women underwent axillary immunolymphoscintigraphy (ILS) shortly before a planned operation for suspected carcinoma of the breast. The aim was to test the feasibility of this procedure for the noninvasive staging of lymph-nodes. Three antibodies were used: HMFG-1 (3 patients), HMFG-2 (13) and 3C6F9 (27). The diagnosis was confirmed in 35 patients. They underwent radical mastectomy with removal of the lymph-nodes. There were marked differences in the usefulness of HMFG-2 and 3C6F9 for ILS in these circumstances. There were too few patients to evaluate HMFG-1. Sensitivity and specificity of the test were 0.57 and 0.83, respectively, for HMFG-1 and 0.83 and 0.93 for 3C6F9. PMID- 3342738 TI - [Diagnostic accuracy of lab tests. An example: the HIV antibody test]. PMID- 3342739 TI - [Intact serum parathormone (PTH 1-84). A suitable parameter for the diagnosis of calcium metabolism disorders]. AB - Intact parathormone (PTH 1-84) was measured with a new immunoradiometric method in serum from 83 children and adults with various abnormalities of calcium metabolism. The results were compared with those of an assay of midregional PTH fraction (44-68). Both measurements discriminated well between normal controls and patients with primary or secondary hyperparathyroidism. In patients in chronic renal failure intact PTH measurement was best for demonstrating parathyroid secretion. An important advantage of the new method is in the diagnosis of PTH hyposecretion in hypoparathyroidism and of tumour hypercalcaemia, which is not possible by mid-regional PTH determination. Intravenous injection of calcium (2 mg/kg over 5 min) and of synthetic PTH fragment (6 U/kg 1-38 hPTH over 2 min) caused a reduction in intact serum-PTH to about half the initial value after five minutes. Measuring intact PTH is thus a suitable method for determining both raised and decreased parathyroid secretion in disease and in the course of function tests. It is simple to perform, subject to only minor interference, and thus suitable also as a routine laboratory test. PMID- 3342740 TI - [Coronary muscle bridges]. PMID- 3342741 TI - [Extracorporeal lithotripsy of gallstones]. PMID- 3342742 TI - Polarized thyroid cells in monolayers cultured on collagen gel: their cytoskeleton organization, iodine uptake, and resting membrane potentials. AB - Porcine thyroid cells were cultured on collagen gel-coated cover glasses. They were reorganized into polarized monolayer cells; the basal cell membranes were in contact with the collagen gel, and the apical ones faced the culture medium. We studied cytoskeleton organization, resting membrane potentials, and iodine uptake of these cells. The quick-freezing and deep-etching replica method provided three dimensional images of the cytoskeleton organization. Networks of microfilaments were observed under the apical cell membrane. In the deep cytoplasm and near the basal cell membranes, intermediate filaments predominated and were interlinked with the microfilaments. When the cells were cultured in the presence of TSH, TSH induced the formation of microvilli at the apical cell membranes and the accumulation of microfilaments under these membranes; in the deep cytoplasm, the intermediate filaments were more closely interlinked with the microfilaments. The microfilaments were immunostained with antiactin antibody. Thus, collagen is a factor in determining the cell polarity, and TSH further augments polarization through reorganizing the cytoskeletons. Electrophysiological study revealed that the resting membrane potential of cells cultured in the absence of TSH was -46 mV, and that of cells cultured in the presence of TSH was -58 mV. TSH hyperpolarized resting membrane potentials. These cells took up iodine. TSH in the medium augmented this uptake. TSH augments thyroid cell polarization through reorganizing the cytoskeletons and hyperpolarizing the resting membrane potentials and enhances iodine uptake by the cells. PMID- 3342743 TI - Characterization of a cytosolic triiodothyronine binding protein in atrium and ventricle of rat heart with different sensitivity toward thyroid hormone levels. AB - Cytosolic T3-binding protein (CTBP) has been identified in both the ventricle and atrium of adult rat hearts. Its biochemical characteristics and concentration have been determined in the two tissues as a function of thyroid hormone level. In both tissues association and dissociation constants were, respectively, k+1 = 1.3 x 10(8) M-1/min and k-1 = 0.025 min-1. Scatchard analysis of T3 equilibrium binding data revealed a single class of binding sites (Ka = 3.8 x 10(8) M-1). The maximal binding capacity (MBC) was 1400 fmol/mg protein in the ventricle and 730 fmol/mg protein in the atrium. The apparent mol wt of CTBP, determined by gel filtration, was 63.000. Among the thyroid hormone analogs tested in ventricular cytosol, D-T3 had the highest affinity, followed by L-T3, L-T4, 3,3',5 triiodothyroacetic acid, and rT3. These characteristics were very similar to those previously described for rat brain, and dog and rat liver and kidney CTBP. In hypothyroid rats MBC was only increased in the atrium (50-100%); after a single injection of T4 (2 micrograms/10 g BW 3 or 18 h before death) values returned to normal in the atrium and declined in the ventricle (-35%). During postnatal development, the highest MBC value (2000 fmol T3/mg protein) was observed in atria on day 10, i.e. when the serum T4 level was still low, and in the ventricle on day 30 (4000 fmol T3/mg protein) when the serum T4 level was at its highest. Binding affinities were similar in the two tissues at all ages studied. It was twice as high in both these tissues during the first week of development than in adulthood. These results favor a thyroid hormone down regulation of the binding capacity of CTBP that would be more sensitive to the hormone in the atrium than in the ventricle. PMID- 3342744 TI - Elevated levels of vitamin D-dependent calcium-binding protein (calbindin-D9k) in the osteosclerotic (oc) mouse. AB - The osteosclerotic (oc) mouse is an osteopetrotic mutation that has recently been identified as having rickets associated with its osteopetrosis. The presence of this rachitic lesion, unexplainable from a nutritional standpoint, prompted an investigation into the vitamin D endocrine system in these animals. The developmental appearance of vitamin D-dependent calcium-binding protein (calbindin-D9k) and alkaline phosphatase was studied in oc mutant and normal mice from birth to weaning, as were serum concentrations of 25-hydroxyvitamin D3 (25OHD3), 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], calcium, and phosphorus. Intestinal and renal calbindin-D9k levels were markedly and precociously elevated (4- to 9-fold) in young suckling, but not newborn, mutant mice compared to values in normal controls. Serum 25OHD3 levels were very low to undetectable in 2-week old mutant mice compared to normal values, while 1,25-(OH)2D3 levels were 6 times higher in mutants. The exact cause of this premature induction in mutants is unknown, but may be due to elevated circulating levels of 1,25-(OH)2D. Alkaline phosphatase activity was similar between phenotypes at all ages. These studies indicate that the rachitic lesion present in oc mutants may be the result of some inherited disorder in vitamin D metabolism in these animals. Alternatively, these data are also consistent with a normal appropriate response to hypocalcemia and hypophosphatemia resulting from decreased osteoclastic bone resorption. PMID- 3342745 TI - Increased plasma clearance rate of thyroxine despite decreased 5' monodeiodination: study with a peroxisome proliferator in the rat. AB - In euthyroid rats a 17-day treatment with nafenopin, a hypolipidemic agent and peroxisome proliferator, decreased serum total and free T4 concentrations to 32 +/- 5% and 62 +/- 8% (mean +/- SEM; n = 10), respectively, with no change in serum T3 and TSH concentrations. In methimazole-treated rats infused with 3 nmol T4/day/100 g BW, the nafenopin inhibitory effect was not significantly different from that in euthyroid rats. Nafenopin treatment had the following effects on peripheral T4 and T3 metabolism in euthyroid rats. The plasma clearance rate of T4 (PCR), which was measured by Alzet minipump infusion of tracer, was increased 2-fold (1.58 +/- 0.09 vs. 0.82 +/- 0.06 ml/h.100 g BW; P less than 0.001; n = 5), while the PCR of T3 was decreased (37.5 +/- 1.3 vs. 53.8 +/- 1.8; P less than 0.001; n = 5). The fecal clearance rate of radioactivity derived from T4 was increased 2-fold (1.93 +/- 0.10 vs. 0.77 +/- 0.07 ml/h.100 g BW), whereas the urinary clearance rate was not significantly modified. The 5'-deiodinase (5'D) activity, measured by deiodination of labeled rT3, was strongly inhibited in liver and kidney, not modified in brown fat and anterior pituitary, and increased in cerebral cortex. In methimazole-treated rats substituted with isopropyl diiodothyronine only hepatic 5'D activity was decreased. It is concluded that the decrease in serum total and free T4, without alteration in serum T3 and TSH concentrations, resulting from nafenopin treatment is mainly due to changes in peripheral T4 and T3 metabolism, since it is also observed in T4-substituted animals. The increased PCR of T4 cannot be explained by an increase in deiodination activity, since the major 5'D pathways are inhibited after nafenopin treatment, and the urinary clearance rate is not modified. It can partly be explained by an increase in the fecal clearance rate of T4, which could be due to an increase in glucoronoconjugation. In addition, nafenopin was found to be a weak competitor of T4 binding to serum proteins, leading to a small increase in the free T4 fraction which might also contribute to the increased T4 PCR. The decrease in T3 PCR remains to be explained. PMID- 3342746 TI - 19-Nordeoxycorticosterone excretion in male and female inbred salt-sensitive (S/JR) and salt-resistant (R/JR) Dahl rats. AB - Rats were selectively bred for susceptibility (S) and resistance (R) to the hypertensinogenic effects of excess salt intake by Dahl and further inbred to virtual homozygosity by Rapp (S/JR and R/JR). The S strain has been shown to have a mutation of the cytochrome P-450-dependent 11 beta,18-hydroxylase resulting in the enhanced production of 18-hydroxydeoxycorticosterone (18-OH-DOC) compared to that of the R strain. It is known that this enzyme is also responsible for the hydroxylation of deoxycorticosterone at the 19 position to produce 19 hydroxydeoxycorticosterone. Recently, the excretion of 19-nordeoxycorticosterone (19-nor-DOC), a potent mineralocorticoid, has been shown to be markedly increased in S/JR females compared to that in R/JR females consuming a high sodium diet. While the S/JR rat is spontaneously hypertensive, the course of the disease is greatly accelerated and exacerbated by a high sodium diet. If, indeed, 19-nor-DOC is responsible for the spontaneous hypertension in the S/JR rat, then its production should also be higher in the S/JR rat consuming a normal salt diet. Furthermore, since its production is suppressed by NaCl intake, the excretion should be even higher when not suppressed by a high sodium diet. We measured the urinary excretion of 19-nor-DOC, 18-OH-DOC, and corticosterone in male and female S/JR and R/JR rats consuming a normal sodium diet. The excretions of corticosterone and 18-OH-DOC were significantly higher by S/JR of both sexes than by R/JR, with the excretion by female rats being higher than that by male rats within the same strain. The hierarchy of excretion rates of 19-nor-DOC was: S/JR females greater than R/JR females greater than S/JR males greater than R/JR male rats. These studies indicate that while S/JR rats of both sexes develop higher blood pressures than the R/JR even on a standard salt intake, the excretion of 19 nor-DOC does not correlate well with their blood pressure elevation, since the normotensive female R/JR rat excretes significantly higher quantities of 19-nor DOC than the hypertensive male S/JR rat. Thus, it is unclear whether 19-nor-DOC is playing a significant role in the pathogenesis of the hypertension in the S/JR rat. It also remains unknown whether the renal site of formation of 19-nor-DOC allows access to the mineralocorticoid target sites in the kidney. PMID- 3342747 TI - Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone-deficient rats. AB - The effects of the nonsteroidal antiestrogen tamoxifen were determined on trabecular bone mass in the proximal tibial metaphysis of intact and ovariectomized rats. Rats were ovariectomized at the beginning of the study. On day 7 of the study, 5-mg slow release pellets of tamoxifen or placebo were implanted sc. All of the rats were killed on day 28 of the experiment. Sections of the proximal tibial metaphysis were stained for acid phosphatase and evaluated histomorphometrically. Ovariectomy resulted in marked loss of bone. Compared to the values in sham-operated animals, the trabecular bone at a sampling site in the secondary spongiosa of ovariectomized rats was reduced by more than 60%, the length of trabecular bone surface covered by osteoclasts was increased by 563%, the percentage of trabecular bone surface covered by osteoclasts was increased by 567%, the mean osteoclast size was increased by 84%, and the number of nuclei per osteoclast was increased by 38%. In contrast, treatment of ovariectomized rats for 3 weeks with tamoxifen restored the histomorphometric measurements to values comparable to those in sham-operated animals. 17 beta-Estradiol increased trabecular bone fractional area in ovariectomized and sham-operated rats, and administration of tamoxifen to estrogen-treated, ovariectomized, and sham operated animals produced a further increase in trabecular bone. In summary, 1) ovariectomy resulted in large increases in both the number and activity of osteoclasts, 2) the increased bone resorption associated with ovariectomy produced a net loss of trabecular bone, and 3) treatment of ovariectomized rats with tamoxifen prevented these skeletal changes. The results indicate that in the rat, tamoxifen mimics the effects of estrogen on trabecular bone at concentrations that are not uterotropic. PMID- 3342748 TI - Prolactin (PRL) receptor induction in cultured rat hepatocytes: dual regulation by PRL and growth hormone. AB - Although early work implicated PRL as the pituitary factor inducing rat hepatic PRL receptors, recent studies indicated that GH, not PRL, was responsible. The roles for these two hormones were evaluated on rat hepatocytes cultured in serum free medium supplemented with insulin (1 microgram/ml), epidermal growth factor EGF (25 ng/ml), glucagon (500 ng/ml), cholera toxin (2 ng/ml), hydrocortisone (10(-8) M), and transferrin (1 microgram/ml) and changed daily. Ovine (o) PRL, bovine (b) GH, or human (h) GH were introduced after 2-4 days of culture, and PRL receptors were measured by determining [125I]hGH binding in the presence and absence of excess oPRL in a total particulate fraction pretreated with 3 M MgCl2. The specific binding of hGH (% per 100 micrograms protein) decreased by 8- to 10 fold (female, 17.9 +/- 0.2% to 1.5%; male, 7.0 +/- 0.1% to 0.7%) after 3 days in culture. When added after 3 days, hGH induced PRL receptors in both female and male cells with the effect being more gradual in the latter. Induction occurred with 10 ng/ml hGH and was maximal [11- to 13-fold control] at 250-1000 ng/ml. bGH and oPRL also induced PRL receptors with maximal levels attained at 250-500 ng/ml oPRL (3- to 4-fold control). The combined addition of oPRL (300 ng/ml) and bGH (300 ng/ml) yielded levels of induction comparable to that seen with hGH. Although hormone treatment restored PRL receptor levels to those seen in male rats, the much higher levels of female rats were not attained. Treatment of hepatocytes with hGH, bGH, or oPRL affected neither cell number (through 10 days of culture) nor PRL receptor affinity. At supramaximal doses hGH, PRL, and bGH down-regulated PRL receptors, but this was particularly noticeable for oPRL and hGH. 17 beta-Estradiol and testosterone added to male and female hepatocytes simultaneously with hGH had little or no effect on receptor induction. We conclude that hepatic PRL receptors are induced by both PRL and GH, each acting through its own receptor. The failure to restore receptor levels to those seen in female rats attests to the importance of other modulators. This dual regulation of the PRL receptor explains the unusual potency of hGH which binds to both PRL and GH receptors. PMID- 3342749 TI - 5 alpha-dihydrotestosterone formation is necessary for embryogenesis of the rat prostate. AB - To determine the role of 5 alpha-dihydrotestosterone (DHT; 17 beta-hydroxy-5 alpha-androstan-3-one) in formation of the embryonic prostate, we quantitated prostatic development in urogenital tracts of control male newborn and offspring of rats treated with a specific 5 alpha-reductase inhibitor (L652,931; Merck, Sharp, and Dohme) during prostate morphogenesis. Treatment with the 5 alpha reductase inhibitor (50 mg/kg.day) from days 14-22 of gestation impaired development of the prostate and virilization of the external genitalia in male offspring compared to those in control animals. However, virilization of the internal genitalia (seminal vesicles, epididymis) was unaffected. Simultaneous administration of DHT (50 mg/kg.day) with the 5 alpha-reductase inhibitor restored prostate development and anogenital distances of males to normal and virilized the external genitalia of females. We conclude that DHT is the active androgen responsible for prostatic development in the rat. PMID- 3342750 TI - Localization of progesterone receptor with monoclonal antibodies to the human progestin receptor. AB - A series of rat and mouse monoclonal antibodies to the human progesterone receptor (PR) has recently been produced. These antibodies were used for the immunocytochemical identification of PR in several mammalian species including humans. The specificity of the monoclonal antibodies for PR was confirmed by using competition studies with purified PR and by comparison of the immunostained tissues, known from steroid binding assays to be receptor rich, with immunostained tissues known to be receptor-poor. Immunoreactive PR was found in the nuclei of uterine epithelial, stromal, and smooth muscle cells; benign ductal and lobular epithelial cells of the breast; ovarian surface epithelium; ovarian stroma and luteal cells; pulmonary parenchymal cells; and selected pituitary parenchymal cells. A proportion of the following selected human tumors expressed PR: breast carcinomas, endometrial carcinomas, ovarian carcinomas, and meningiomas. PR was localized to the nuclei of all progesterone target tissues even under conditions where the vast majority of the receptor is unoccupied by steroid, suggesting that the unoccupied as well as the steroid-occupied form of PR are predominantly nuclear proteins, as observed previously for estrogen receptor and rabbit PR. PMID- 3342751 TI - Effect of L-thyroxine administration on the incidence of iodine induced and spontaneous lymphocytic thyroiditis in the BB/Wor rat. AB - Chronic L-thyroxine administration (6 micrograms/100g BW, ip, daily) for 2 or 3 months suppressed serum TSH concentrations and decreased both the incidence of spontaneous lymphocytic thyroiditis (LT) and the serum levels of anti thyroglobulin (anti-Tg) antibodies in the diabetes prone BB/Wor rat. This suggests that TSH may play a role in the occurrence of LT in this rat model. In contrast to these observations, L-thyroxine administration did not affect the markedly increased incidence of LT or the elevated serum anti-Tg antibodies in iodine supplemented BB/Wor rats, suggesting that TSH stimulation is not necessary for the development of iodine induced LT in this rat model. Other factors, such as the increased antigenicity of highly iodinated Tg, may be more important. PMID- 3342752 TI - Sexual differences in glomerular ultrafiltration: effect of androgen administration in ovariectomized rats. AB - The glomerular ultrafiltration rate varies as a function of age and sex. To further elucidate the basis for the sexual difference, an androgen [Deca Durabolin (DECA)] was administered to female ovariectomized rats, and glomerular hemodynamics were evaluated by renal micropuncture after 6 and 16 weeks of therapy. Results were compared to those in control ovariectomized female rats injected with vehicle. Therapy did not produce significant differences in body weight, but kidney size was modestly increased in DECA-treated rats at 6 weeks (0.68 +/- 0.03 vs. 0.86 +/- 0.03 g wet weight; P less than 0.05); at 16 weeks major differences in renal size were documented (0.69 +/- 0.03 vs. 1.18 +/- 0.05 g wet weight; P less than 0.01). The increase in size was primarily due to tubular hypertrophy, with more modest increases in glomerular size. After 6 weeks of therapy, the single nephron glomerular filtration rate (SNGFR) was increased in DECA-treated ovariectomized rats (24.8 +/- 1.0 vs. 32.9 +/- 1.1 nl/min; P less than 0.01). Whole kidney glomerular filtration rate also rose in proportion to increases in kidney size. The greater SNGFR was attributed to higher rates of nephron plasma flow and a numerical increase in the glomerular ultrafiltration coefficient. However, after 16 weeks of androgen therapy, in spite of marked renal hypertrophy, SNGFR did not further rise in proportion to renal size, and the rate of nephron plasma flow and the glomerular ultrafiltration coefficient actually fell relative to those in control untreated rats. Light microscopic evaluation of renal tissue revealed no abnormalities in DECA-treated rats. Thus, 6-week androgen therapy to ovariectomized female rats increased both glomerular ultrafiltration rates and renal size. However, with prolonged administration a glomerular dysfunction may have ensued whereby glomerular ultrafiltration was dissociated from increases in renal size. PMID- 3342753 TI - The source of relaxin in pregnant Syrian hamsters. AB - Serum immunoreactive relaxin (IR) was measured on days 8, 10, and 14 of gestation in intact and ovariectomized (day 8 of pregnancy) hamsters. In intact hamsters, IR increased from 3-4 ng/ml on day 8 to 20 ng/ml by day 14 of pregnancy. After ovariectomy on day 8, pregnancy failed, and IR decreased rapidly to 0.29 ng/ml on day 14. However, when pregnancy was maintained in ovariectomized hamsters by daily injections of 0.1 microgram 17 beta-estradiol and 4 mg progesterone, serum IR rose to levels similar to those in intact hamsters on days 10 and 14 of pregnancy (i.e. 15 and 20 ng/ml, respectively). Placentas were obtained from other groups of hamsters on days 11, 14, and 15 of pregnancy and homogenized for bioassay by the classical guinea pig pubic symphysis palpation bioassay. Homogenates of placentas obtained on days 14 and 15 contained, respectively, 4 and 10 micrograms eq porcine relaxin/serum relaxin/g fresh tissue. The placenta, rather than the ovary, appears to be the source of during pregnancy in the hamster. PMID- 3342754 TI - The effect of thyroid dysfunction and fasting on placenta inner ring deiodinase activity in the rat. AB - The placenta contains iodothyronine 5-deiodinase activity (P5-Dase) that probably acts on iodothyronines in the fetal circulation to convert T4 to rT3 and T3 to 3,3'-T2. Since thyroid status and fasting have profound effects on iodothyronine deiodinases in other tissues, the present studies were performed to determine if these perturbations affected P5-Dase. Control and treated rats were mated and killed near term on the 20th day of gestation. P5-Dase was determined in placenta homogenates enriched with dithiothreitol by measuring the conversion of T4 to rT3. In four of five studies, P5-Dase was similar in dams that underwent thyroidectomy (Tx) on day 7 of gestation and sham Tx dams. P5-Dase was not altered in dams that were treated with methimazole (MMI) to induce maternal and fetal hypothyroidism. Treatment of dams with supraphysiological doses of T4, beginning on the seventh day of gestation, did not significantly affect P5-Dase. In three of four studies, P5-Dase was similar in fed dams to values in dams fasted for the last 5 days of pregnancy. Placenta iodothyronine 5'-deiodinase activity (P5'-Dase) was also measured in some studies. P5'-Dase was not decreased in Tx rats and was modestly decreased in MMI-treated rats. However, the effect of MMI was not reversed by the administration of supraphysiological doses of T4, Tx, MMI treatment, and fasting all decreased hepatic T4 5'-deiodinase activity in pregnant rats. These results strongly suggest that thyroid status and fasting do not alter P5-Dase activity. PMID- 3342755 TI - Local versus systemically mediated effects of estrogen on normal mammary epithelial cell deoxyribonucleic acid synthesis. AB - While it has been shown that estrogen promotes mammary gland growth in vivo, it has not been demonstrated if estrogen acts locally in the mammary gland to produce a mitogenic effect in the epithelial cells or if the mitogenic effect is mediated systemically. The purpose of this study was to distinguish between local vs. systemically mediated modes of estrogen action in normal mammary glands of both immature 5-week-old and sexually mature 10-week-old mice. Elvax 40P, noninflammatory, easily manipulated implant material, was combined with 17 beta estradiol and placed either directly into the mammary gland to elicit a localized effect or implanted sc to produce a systemic effect. The effect of estrogen on epithelial cell proliferation was assessed by its effect on mammary gland morphology from whole mount examinations and on DNA synthesis by DNA histoautoradiography. The effects of implant location and estrogen dose on mammary and uterine progesterone receptor (PgR) concentrations were also analyzed. The results indicate that estrogen can act locally to stimulate increased epithelial DNA synthesis and an increase in end-bud size in the immature mammary gland. By contrast, no localized effect of estrogen could be demonstrated in the mature mammary gland; it appears that increased epithelial DNA synthesis and ductal side-branching are systematically mediated effects of estrogen. On the other hand, in the case of PgR regulation, estrogen can act locally to increase receptor concentration in the adult gland. In contrast, in the immature mammary gland only low levels of PgR were detectable, and they could not be increased by any method of estrogen treatment. Thus, these results demonstrate that estrogen can act either locally or systemically to produce mitogenic effects on mammary epithelium. However, the age and/or developmental stage of the target tissue are important factors that determine the hormonal responsiveness of normal tissue and which mode (local vs. systemic) of estrogen action will be operative. PMID- 3342756 TI - Functional differences in cholesterol ester hydrolase and acyl-coenzyme A/cholesterol acyltransferase between the outer and inner zones of the guinea pig adrenal cortex. AB - Previous studies clearly demonstrated that cells isolated from the chromatically distinct inner (primarily zona reticularis) and outer (zona fasciculata and zona glomerulosa) zones of the guinea pig adrenal cortex have vastly different steroidogenic capabilities; the outer zone produces far more cortisol than the inner zone, and mitochondrial cholesterol side-chain cleavage activity in the inner zone is not modulated by ACTH. Thus, in this study we have investigated the characteristics and properties of cholesterol ester hydrolase (CEHase) and acyl coenzyme-A/cholesterol acyltransferase (ACAT) in the outer and inner zones of the guinea pig adrenal to clarify the zonal difference in cholesterol metabolism. CEHase showed two pH optima at around pH 4.5 and pH 7.5 in the outer zone, while optimum activity in the inner zone was found only around pH 4.5, suggesting a lack of neutral CEHase in the inner zone. The acid CEHase was found mainly in the lysosomal fraction, and the neutral CEHase was located mainly in the microsomal fraction. The neutral CEHase activity in the outer zone was significantly enhanced by ether stress, while the acid CEHase activity was not changed in either of the two zones by stress. The basal activity of ACAT was significantly higher in the outer zone than in the inner zone. The present experiments also demonstrated that the inner zone always showed lower ACAT activity than the outer zone even when added cholesterol exogenously. It is suggested that the relatively low activity of ACAT may not always be explained by the reduced content of cholesterol in the microsomal fraction of zona reticularis. ACAT activity in the outer zone was significantly decreased by ether-induced stress, but that in the inner zone was not changed. The content of esterified cholesterol in whole homogenate and the microsomal fraction was significantly decreased in the outer zone, but not in the inner zone, by ether stress. Thus, the decrease in esterified cholesterol after ether stress seems to relate to increased neutral CEHase activity and decreased ACAT activity in the outer zone. The present observation clearly indicates that the lack of neutral CEHase and the lesser activity of ACAT in the inner zone than in the outer zone may contribute to the impaired cholesterol metabolism in the inner zone. PMID- 3342757 TI - Electrical stimulation of ascending noradrenergic tracts in the midbrain: suppression of steroid-induced luteinizing hormone release. AB - This study examined the effects of electrical stimulation of the dorsal and ventral ascending noradrenergic tracts in the central nervous system [dorsal (DNT) and ventral (VNT) noradrenergic tracts] during an ongoing LH surge induced by ovarian steroids. A bipolar electrode was implanted in the midbrain of ovariectomized rats, in the region of either the DNT or VNT. One week later the rats were given estradiol benzoate (10 micrograms/100 g BW), followed 3 days later by an injection of progesterone (2 mg) at 1100 h. This steroid treatment resulted in a LH surge in the afternoon which peaked at approximately 1800 h. Biphasic electrical stimulation (50-100 microA; 400 musec; 30 Hz) was applied to the conscious unrestrained rats for 1 h beginning at 1600 h. Electrical stimulation of the DNA (n = 10) for 1 h resulted in significantly lower LH levels at 1700 h. Similar electrical stimulation of the VNT (n = 8) also markedly suppressed LH release at 1700 h. Electrical stimulation of brain sites close to but outside the DNT or VNT were ineffective. After the cessation of electrical stimulation, LH levels began to rise again and at 1900 h were not significantly different from levels in the control rats. To determine if the recovering LH surge could be interrupted further, the effects of a second electrical stimulating session, 2 h after the first one, was investigated in other groups of animals. As expected, electrical stimulation of either the DNT or VNT between 1600 and 1700 h resulted in a transient suppression of the steroid-induced LH surge. The mean LH levels of these animals were on the rise between 1700 and 1900 h. Dramatically, a second electrical stimulation applied to the DNT or VNT from 1900-2000 h again inhibited LH release. Thus, the LH release pattern in these twice-stimulated rats was significantly different from that in either the nonstimulated controls or animals that had received only one electrical stimulation session (at 1600 h). Treatment of the rats with an alpha-adrenergic blocker (phenoxybenzamine) reversed the inhibitory effect of DNT activation on the LH surge. Treatment with a beta-adrenergic blocker (propranolol) or a dopamine antagonist (pimozide) was ineffective. These data demonstrate that, similar to intraventricular infusion of norepinephrine, activation of the ascending norepinephrine fibers results in interruption of the steroid-induced LH surge. PMID- 3342758 TI - Effects of thyrotropin on the vascular conductance of the thyroid gland. AB - It is well established that TSH from the anterior pituitary is the principal stimulatory agent in the physiological regulation of the thyroid gland. Chronic elevations of plasma TSH induce hyperplasia and hypertrophy of thyroid follicular cells and enlargement of blood capillaries. At low plasma TSH levels the thyroid gland atrophies. We have examined the vascular conductance (C = blood flow/mean arterial pressure) of the thyroid gland and several other tissues over a wide range of endogenous plasma TSH concentrations and after treatment with bovine TSH (bTSH) in rats. Tissue blood flows were determined using 15 +/- 5-microns diameter 141Ce-labeled microspheres in a modification of the reference sample microsphere technique. The microspheres were injected directly into the left cardiac ventricle via a 23-gauge needle passed through the chest wall, while the reference blood sample was collected and systemic arterial blood pressure was monitored through femoral arterial catheters. After the animals were killed, tissues were cleaned and weighed, and the tissue radioactivity was determined. Blood samples for determination of plasma hormone levels were obtained from the jugular vein before the injection of microspheres. In the first series of experiments, the vascular C per mass of thyroid gland was significantly decreased 4 and 8 days after hypophysectomy. Treatment of hypophysectomized rats with bTSH (185 mU/100 g.day as a continuous iv infusion for 2 or 6 days) restored thyroid vascular C per mass of tissue to control levels. In the second series of experiments, we manipulated circulating plasma TSH levels in intact rats by 6 days of treatment with propylthiouracil (2.0 mg/day, ip), thyroid hormones (1.5 micrograms T4, 0.4 micrograms T3 or 3.0 micrograms T4, plus 0.8 micrograms T3/100 g.day, sc by continuous infusion), TRH (240 micrograms/day, iv, by continuous infusion), bTSH (800 mU/day, iv, by continuous infusion), or combinations of these treatments. The vascular C per mass of thyroid gland was significantly decreased at very low chronic plasma TSH levels and increased at very high chronic plasma TSH levels. Thyroid vascular C per mass was unchanged, however, over a broad intermediate range of plasma TSH concentrations encompassing normal values, despite alterations in the size and function of the thyroid gland. At these intermediate levels of TSH stimulation, the thyroid gland may respond by adding or subtracting functional units without changing the blood flow per unit. The amount of blood flow per functional unit may be altered only at very high or very low levels of TSH stimulation. PMID- 3342759 TI - Lysophosphatidylinositol: a potential mediator of 1,25-dihydroxyvitamin D-induced increments in hepatocyte cytosolic calcium. AB - Recent studies in our laboratory demonstrate that 1,25-dihydroxyvitamin D [1,25 (OH)2D] increases hepatocyte cytosolic calcium in the absence of extracellular calcium and activates phospholipase-A-induced deacylation of phosphatidylinositol within 5 min. To determine whether inhibition of phospholipase-A affects D induced increments in cytosolic calcium and which metabolite of phosphatidylinositol mediates these increments, cytosolic calcium is measured in cultured hepatocytes, loaded with Fura 2AM. Cellular fluorescence is determined at excitation wavelengths of 340 and 380 nm, and cytosolic calcium is calculated. 1,25-(OH)2D treatment for 5 min increases cytosolic calcium levels in the cultured hepatocyte. Inhibition of phospholipase-A with bromophenacylbromide blocks the vitamin D effect on cytosolic calcium, indicating that phospholipase-A activation precedes increments in cytosolic calcium. Neither arachidonic acid nor sodium arachidonate affects cytosolic calcium. In contrast, LPI increases hepatocyte cytosolic calcium in the presence and absence of extracellular calcium. The effect is not blocked by bromophenacylbromide. Neither cell viability nor supernatant fluorescence is altered by LPI, indicating that LPI is increasing fluorescence within the cell. 1,25-(OH)2D treatment for 5 min increases cytosolic pH in cultured hepatocytes. Inhibition of cell alkalinization with amiloride blocks the vitamin D effect on both cytosolic pH and cytosolic calcium, but not the effect of LPI on calcium. NH4Cl increases hepatocyte pH but not cytosolic calcium. The results indicate that phospholipase-A activation is necessary for 1,25-(OH)2D-induced increments in hepatocyte cytosolic calcium and that LPI, a deacylation product of phosphatidylinositol, mediates these increments. Furthermore, inhibition of Na+/H+ exchange, while not blocking the ability of the cell to increase cytosolic calcium in response to LPI, prevents the 1,25-(OH)2D-induced increments in both pH and calcium. The data suggest that the rapid effects of 1,25-(OH)2D on hepatocyte calcium are preceded by cell alkalinization and phospholipase-A activation, and these effects appear to be linked to the Na+/H+ antiport system and not nonspecific cell alkalinization. PMID- 3342760 TI - Regulation of progesterone receptor messenger ribonucleic acid and protein levels in MCF-7 cells by estradiol: analysis of estrogen's effect on progesterone receptor synthesis and degradation. AB - The human breast cancer cell line MCF-7 responds to estrogens with increased progesterone receptor (PR) levels. In this study, we use dense amino acid density shift analyses to address directly the question of whether estrogen increases PR levels in MCF-7 cells by altering rates of receptor synthesis and/or degradation. Using different concentrations of estradiol (E2), which achieve PR levels that are half-maximal (3 X 10(-11) M F2) or maximal (6 X 10(-11) M E2), we have done sucrose gradient density shift analyses using dense (15N, 13C, 2H) amino acid incorporation to study rates of PR synthesis and degradation. These studies reveal a nonlinear loss of preexisting normal density receptor with time. From kinetic modeling analyses, equivalent rates of degradation are estimated for PR whether maximal or half-maximal levels are maintained, indicating that the major effect of E2 on PR content is to increase the rate of PR synthesis while leaving the degradation rate unaltered. The E2-stimulated increase in PR protein is also associated with increased levels of PR mRNA, as demonstrated by the use of a human PR cDNA probe. These density shift data provide evidence that the increased PR levels after estrogen exposure in MCF-7 cells are the result of an increased rate of receptor synthesis, rather than modulation of the rate of receptor degradation. PMID- 3342761 TI - Oxytocin and vasopressin gene expression in the hypothalamo-neurohypophyseal system of the rat during the estrous cycle, pregnancy, and lactation. AB - To study the state of hypothalamic expression of the oxytocin (OT) and vasopressin (VP) genes in different conditions of the female rat, OT and VP mRNA levels were determined during the estrous cycle, pregnancy, and lactation. OT and VP mRNA levels of the supraoptic nucleus were quantified by Northern blot and dot blot analysis. OT and VP contents of the pituitary gland were determined by RIA. During the estrous cycle, OT mRNA levels of the supraoptic nucleus were significantly increased 1.5- to 2-fold at estrous relative to the other periods of the cycle. No significant cyclic variation was observed in VP mRNA levels. The OT content of the pituitary gland was significantly decreased at estrus and also the VP contents showed a cyclic variation with the lowest levels occurring at estrus and metestrus. At the last day of gestation a 3- and 2-fold increase of OT mRNA and VP mRNA, respectively, was measured, but no changes were observed at gestational day 12, 15, and 18. In rats lactating for 15 days, OT and VP mRNA levels were approximately 3-fold higher than during the estrous cycle. Concomitantly the OT and VP contents of the pituitary gland were decreased by approximately 50%. It is concluded that both OT and VP gene expression are stimulated just before birth and during lactation indicating that both genes are sensitive to common factors. A dissociation of the regulation of the OT and VP genes occurs in the estrous cycle. PMID- 3342762 TI - The circulating growth hormone (GH)-binding protein complex: a major constituent of plasma GH in man. AB - The recent discovery of a specific binding protein for human GH (hGH) in human plasma suggests that hGH circulates in part as a complex in association with the binding protein(s). However, the magnitude of the complexed fraction prevailing under physiological conditions is unknown because of 1) dissociation of the complex during analysis and 2) potential differences in the binding characteristics of radiolabeled and native hGH. We conducted experiments designed to minimize dissociation during analysis (gel filtration in prelabeled columns, frontal analysis, and batch molecular sieving) with both native and radioiodinated hGH. All three methods yielded similar estimates for the complexed fraction. In normal plasma the bound fraction for 22 K hGH averaged 50.1% (range, 39-59%), that for 20 K hGH averaged 28.5% (range, 26-31%). Above a hGH level of about 20 ng/ml the bound fraction declines in concentration-dependent manner due to saturation of the binding protein. We conclude that a substantial part of circulating hGH is complexed with carrier proteins. This concept has important implications for the metabolism, distribution, and biological activity of hGH. PMID- 3342763 TI - Inhibitory action of leumorphin on vasopressin secretion in conscious rats. AB - To elucidate the role of leumorphin, a kappa-agonist derived from proenkephalin-B (neoendorphin/dynorphin precursor), in the control of arginine vasopressin (AVP) secretion, we examined the effects of intracerebroventricular (icv) administration of leumorphin on AVP secretion under basal and stimulated conditions in conscious unrestrained rats. Intracerebroventricular injection of leumorphin (60 or 600 pmol) significantly inhibited basal AVP secretion. In 72-h water-deprived rats, icv injection of leumorphin (60 or 600 pmol) also suppressed AVP secretion in a dose-dependent manner. The AVP response induced by icv injection of angiotensin II (100 pmol) was significantly decreased by the simultaneous icv injection of leumorphin (6-600 pmol) in a dose-dependent manner. Intracerebroventricular administration of leumorphin (600 pmol) also reduced the AVP secretion stimulated by icv injection of carbachol (50 pmol). Intravenous pretreatment with naloxone (0.5 mg/kg BW) diminished the inhibitory action of leumorphin (60 pmol) on AVP secretion. However, no effect on AVP secretion was observed after iv injection of leumorphin (600 pmol). These results indicate that leumorphin possesses a potent inhibitory effect on AVP secretion, suggesting its important role in the regulation of AVP secretion in the brain. PMID- 3342764 TI - Hormonal regulation of pseudocholinesterase activity in cultured rat hepatocytes. AB - Plasma pseudocholinesterase (PsChe) activity was examined in adult female rat hepatocytes isolated by collagenase perfusion and maintained in a chemically defined medium supplemented with dimethyl sulfoxide. Time course studies on PsChe activity in cultured hepatocytes indicate that cells maintained in a chemically defined medium lacking human GH and 17 beta-estradiol (E2) exhibit a decrease in activity after the first 3 days in culture followed by a stabilization of PsChe activity for up to 15 days. GH (0.02, 0.2, and 2 micrograms/ml) increased PsChe activity in a dose-dependent manner. Addition of E2 (10(-5)-10(-7) M) alone to hepatocyte cultures did not cause an increase in PsChe activity. The increases produced by both the 2 micrograms/ml and 0.2 micrograms/ml GH doses plus E2 (10( 7) M) were significantly greater than controls and similar to the increase produced by GH alone. The ability of the hepatocytes to express PsChe activity was not dependent upon the continuous exposure of the cells to GH, since control cultures, maintained for 12 days in medium lacking GH, were able to express a high level of PsChe activity after the addition of GH (2 micrograms/ml) on day 12. This increase was observed in hepatocytes in culture for 30 days. These results indicate that GH plays a pivotal role in the regulation of PsChe activity in vitro, and that under the conditions used in this study, E2 does not influence the ability of hepatocytes in culture to express this enzyme. PMID- 3342765 TI - Endoscopic diagnosis and management of complications after vertical banded gastroplasty. PMID- 3342766 TI - Endoscopic sphincterotomy: long-term results in 408 patients with complete follow up. AB - Endoscopic sphincterotomy was performed in 469 patients for the treatment of biliary calculi, with procedure-related morbidity of 6.3% and mortality of 0.4%. Long-term follow-up to 10.5 years (mean 3.7 years) was completed in all of 408 patients at least six months postsphincterotomy. Recurrent stones developed in 21 patients (5.8%) after a mean of 2.4 years (range 4 months to 7 years); in 6 after 3 years. Eight patients reformed stones more than twice at a mean interval of 1.8 years (range, 5 months to 3.5 years). In the 122 patients with gallbladders in situ, acute cholecystitis occurred in 5 of 31 with gallstones (16%), but in none of the 91 without gallstones. In the 237 patients who had undergone cholecystectomy, 4 late deaths occurred secondary to recurrent choledocholithiasis and cholangitis. In the 49 patients with primary intrahepatic stones, 3 late deaths occurred secondary to hepatic abscess. These results suggest that (a) endoscopic sphincterotomy is a very effective procedure in long term follow-up, (b) cholangiography should be done at the appearance of slight abdominal symptoms even after 3 years, (c) patients who have ever reformed stones should undergo cholangiography yearly for at least 4 years, and (d) cholecystectomy is recommended for patients with gallbladders after sphincterotomy, only if gallstones are present. PMID- 3342767 TI - Early colorectal cancer--follow-up after endoscopic polypectomy. AB - Approximately 90% of correctly indicated endoscopic polypectomies for early colorectal cancer, whether invasive or not, are curative, provided strict criteria are adopted in the pathological evaluation of the resected specimen. Unrestricted time surveillance is mandatory since benign (more frequent) or malignant relapses appear in 30-40% of the patients. PMID- 3342769 TI - Endoscopic treatment of a pancreatic pseudocyst by naso-cystic tube. AB - Pancreatic pseudocysts can be treated by endoscopic procedures. We report a case in which a naso-gastric tube, endoscopically placed through a cysto-gastrostomy, permitted the successful drainage of a large pancreatic pseudocyst without any recurrence. PMID- 3342768 TI - Local epinephrine injection improves the therapeutic effect of Nd-YAG laser treatment of arterial peptic ulcer bleeding. AB - Nd-YAG laser therapy has been shown to be effective in the treatment of gastrointestinal ulcer bleeding. However, a breakdown by bleeding severity shows that its benefit is doubtful in bleeds classified as Forrest Ia and IIa. In a prospective study, we therefore tested a new therapeutic approach combining epinephrine injection into the bleeding site, with subsequent laser coagulation. Thirty-two patients with Forrest Ia and IIa bleeding from gastric or small intestinal ulcers were compared with 51 own historical controls treated by laser coagulation alone. In the combined therapy group, a significantly higher rate of permanent hemostasis was achieved, and mortality and frequency of emergency surgery were significantly reduced. Furthermore bleeding recurred more rarely and only during the later course of the disease. Finally, following epinephrine injection fewer Forrest IIa ulcer bleeds were reactivated by laser treatment, and all of these bleeds were stopped by further laser coagulation. Overall, our results demonstrate a clear-cut therapeutic improvement when laser coagulation is preceded by local epinephrine injection. PMID- 3342770 TI - ERCG: endoscopic retrograde catheterization of the gallbladder. AB - This report describes a newly developed catheter system with the aid of which the cystic duct and gallbladder can be reliably catheterized, retrograde, via an endoscope. In 8 out of 10 autopsy preparations, transpapillary gallbladder catheterization was successfully achieved, with an average fluoroscopic duration of 12 minutes (range: 4-20 minutes). Neither macroscopic nor microscopic traumatization of the gallbladder was observed. The procedure described in this paper opens up a diagnostic and therapeutic approach to the gallbladder. PMID- 3342771 TI - Biliary pseudocyst. A rare consequence of an iatrogenic lesion of the bile ducts. AB - A patient with a biliary pseudocyst due to an iatrogenic lesion of the hepatic duct is reported. The pseudocyst caused compression of the bile duct with progressive jaundice. Diagnostic problems and the utility of ERCP and PTC in determining the exact site of the lesion for surgical treatment are reported. PMID- 3342772 TI - Localized phlegmonous gastritis: endoscopic view. AB - A case of localized phlegmonous gastritis is reported. Features of this condition and the diagnostic and therapeutic usefulness of endoscopy are briefly considered. PMID- 3342773 TI - Non-surgical endoscopic transpapillary treatment of ruptured echinococcus liver cyst obstructing the biliary tree. PMID- 3342774 TI - Vasoconstrictive properties of epinephrine. PMID- 3342775 TI - Contamination of endoscopic equipment. PMID- 3342776 TI - Squamous cell papilloma of the esophagus. Report on 35 endoscopic cases. AB - We herein report our experience of 35 cases of esophageal squamous cell papilloma (ESP), diagnosed among 8,095 consecutive upper gastrointestinal endoscopies, and histologically confirmed. The incidence (0.45%) was higher than previously reported. Macroscopically, ESP presented with several distinctive features, thus endoscopy permitted great diagnostic accuracy. Most of the papillomas were located in the middle-third of the esophagus, and no significant association with hiatal hernia and reflux esophagitis was seen. The lesion did not recur after removal either by forceps or by diathermic snare. PMID- 3342777 TI - Electronic video endoscopy: preliminary results of imaging modification. AB - This study represents a preliminary trial of the quantification of colorimetric modification of the esophageal mucosa, permitting the opening up of a video electronic and computer classification of lesions of esophagitis. PMID- 3342778 TI - Transition from normal to hypersecretory bronchial mucus in a canine model of bronchitis: changes in yield and composition. AB - Density-gradient analysis was used to follow the transition from normal to hypersecretory bronchial mucus in a model of bronchitis induced in dogs by chronic exposure to SO2 gas. Aspirates of saline bronchial lavage were obtained by fiberoptic bronchoscopy from dogs before, during a 6- to 9-month exposure period to SO2 gas, and during a recovery period of similar duration. Prior to SO2 exposure, aspirates from all animals had a low yield of nondialyzable macromolecules (15 +/- 6 mg/aspirate) and similar composition. Specifically, epithelial glycoprotein of typical buoyant density was not detected; rather a glycoconjugate of higher buoyant density with features of both proteoglycan and glycoprotein was identified. Neutral lipids were predominant with lesser amounts of phospholipids; no glycolipids were detected. During the SO2 exposure period, aspirates from five of the eight dogs contained components similar in buoyant density to human bronchitic glycoprotein. Glycoprotein isolated from the canine aspirates was similar to glycoprotein isolated from human chronic bronchitic sputum, having the same carbohydrate composition and range of oligosaccharide size. Further, during and after SO2 exposure some aspirates contained appreciable amounts of glycolipids. These data demonstrate substantial similarities in composition between normal human and canine mucus and in mucus isolated from dogs with chronic airway inflammation induced by repeated irritant exposure and from human patients with chronic bronchitis. PMID- 3342779 TI - Effect of lactate on glucose incorporation into fetal lung phospholipids. AB - Fetal rabbit lung explants were incubated with 3.0 mM glucose and varying levels of lactate. An increase in lactate concentrations resulted in a decrease in glucose incorporation into total disaturated phosphatidylcholine. Glucose utilization for surfactant phosphatidylcholine synthesis was also reduced by approximately 35% in the presence of 5.0 mM lactate. The decreased incorporation of glucose occurred in the fatty acid portion of both total tissue disaturated phosphatidylcholine and surfactant phosphatidylcholine. The effect of lactate on glucose incorporation into pulmonary phospholipids was not affected by the presence of pyruvate in concentrations up to 500 microM. Pyruvate alone produced only a slight decrease in glucose utilization for lung phospholipid production. These data indicate that glucose and lactate are competitive substrates for late gestation surfactant phospholipid fatty acid synthesis, and that lactate is potentially a very important substrate for fetal lung development. PMID- 3342781 TI - Deposition and retention patterns for 3-, 9-, and 15-micron latex microspheres inhaled by rats and guinea pigs. AB - This study was designed to determine the deposition patterns and fate of large particles inhaled by two species of small laboratory animals during nose breathing. Rats and guinea pigs inhaled 3-, 9-, or 15 micron polystyrene latex microspheres labeled with 46Sc. Approximately 1.4% and 0.55% of the initial internally deposited body burden of 3-micron microspheres was in the alveolar region of the respiratory tract of rats and guinea pigs, respectively. None of the 9- or 15-micron microspheres were detected in the alveolar regions of the rats or guinea pigs. Ninety-five to 99% of the deposited microspheres cleared from these animals with biological half-times of 0.5-1.0 day. Most of the cleared radioactivity was in the feces. Approximations for long-term biological half times for alveolar retention of the 3-micron microspheres were 63 days for rats and 83 days for guinea pigs. About 1% of the initial lung burden of 3-micron microspheres was translocated from lung to lung-associated lymph nodes in both species; none of the 9- or 15-micron microspheres were detected in those lymph nodes. Small fractions of the microspheres initially deposited in the airways of the head were retained with biological clearance half-times ranging from 9 to 350 days. Results from this study do not allow projections for deposition and retention patterns for similar particles inhaled by humans. Such projections must come from studies with humans, or from studies with animal species having deposition patterns for inhaled materials more comparable to those of humans. PMID- 3342782 TI - Postdoctoral education and training for clinical service providers in health psychology. AB - It was recommended by the 1983 National Working Conference on Education and Training in Health Psychology (Stone, 1983) that 2 years of postdoctoral education and training be mandated for future licensed health service providers in health psychology. The background for requiring this postdoctoral training, a model for education, criteria for developing programs, issues of funding, and a rationale for accepting this mandate are presented. Highlighted are the stable and consistent growth of health psychology, the need to expand the period of clinical training to meet the many advances in the field, and the challenges that exist for the fully trained clinical health service provider. PMID- 3342780 TI - Oral N-acetylcysteine speeds reversal of cigarette smoke-induced mucous cell hyperplasia in the rat. AB - We set out to determine whether or not the "mucolytic" drug N-acetylcysteine would speed the reversal of cigarette smoke-induced secretory-cell hyperplasia to normal, similar to that found previously for two nonsteroidal antiinflammatory drugs. Cigarette smoke alone significantly (p less than 0.01) increased the number of secretory cells in seven out of eight airway levels studied and maintained a significant increase in five of the levels at least 3 weeks after cessation of exposure. Treatment of rats with N-acetylcysteine, as 1% of their drinking water during the recovery period, reduced the time taken for secretory cell number to return to normal to between 4 days and 3 weeks, depending on airway level. PMID- 3342783 TI - Long-term nurse-patient interactions: factors in patient compliance or noncompliance to the dietary regimen. AB - Noncompliance to treatment regimens is a widespread, costly problem. The present study examines nurse-patient interactions as factors in compliance/noncompliance to the hemodialysis dietary regimen. Several research studies have evidenced these interactions to be central to patient compliance. However, no research has been reported that has controlled for the nature of the treatment regimen; rather, practitioners' interactions with patients who are being treated for a variety of disorders have been examined. An interaction-process-analysis technique was used to code the verbal behaviors that occur during treatment between 38 hemodialysis outpatients with chronic renal disease and the nurses who provide their treatment. These verbal interactions were analyzed in relation to levels of dietary compliance/noncompliance of patients and length of nursing tenure. It was found that emotionally positive and negative responses by nurses were both positively associated with noncompliance to the dietary regimen; however, treatment-related responses by nurses were not associated with compliance/noncompliance level. With regard to length of nursing tenure, it was found that emotionally positive and negative responses by patients were positively associated with nursing tenure and that treatment-related questions by nurses were negatively associated with nursing tenure. PMID- 3342784 TI - Long-term relationship between weight and aerobic-fitness change in children. AB - The relationship between changes in relative weight and fitness was assessed 5 years after children began treatment for obesity. Multivariate regression analysis showed that two factors were independently related to fitness change: (a) maintenance of weight loss from the end of 6 months of treatment to the 5 year follow-up and (b) initial fitness level. Children who showed the largest long-term changes in relative weight and the lowest initial fitness showed the largest improvements in fitness. Short-term weight loss was not related to long term fitness change. These results show that weight loss and fitness are related over 5 years. PMID- 3342785 TI - Fine structural changes in electrostimulated human skeletal muscle. Evidence for predominant effects on fast muscle fibres. AB - Physical education students were subjected to electrical stimulation of relatively high frequency and current amplitude for 19 days. A quantitative study of several morphological parameters was performed on biopsy samples from gastrocnemius, using stereological methods at both light and electron microscopic levels. The main results were: muscle fibre size was increased; nuclear volume was also increased, suggesting that a proliferation of nuclei had occurred; this was paralleled by an increased content of nuclear DNA. The size of single myonuclei was increased, and their heterochromatin fraction was decreased, these changes being most pronounced in type II fibres. The increase in the mitochondrial fraction was also greatest in type II fibres. It is concluded that this type of electrical stimulation has predominant effects on type II fibres. PMID- 3342786 TI - Alterations in plasma volume, electrolytes and protein during incremental exercise at different pedal speeds. AB - We investigated the effects of pedal speed on changes in plasma volume, electrolytes and protein during incremental exercise. Ten adult males participated in two, 30 minute incremental cycle ergometer exercise tests at room temperature (22 degrees C, rh = 56%). Exercise load was increased from 20 to 70% of peak VO2. Five minutes were spent at each of six stages which were equally spaced in exercise intensity. Subjects pedaled at 50 (50 RPM) and 90 (90 RPM) rev.min-1. Venous blood samples were drawn prior to exercise and during the last minute of each stage. Relative plasma volume changes showed a progressive hemoconcentration during the exercise. There were no significant differences due to pedal speed as plasma volume loss averaged -7.3% during exercise. [Na+], [Cl ], and [K+] increased significantly during exercise but were not influenced by pedal speed. Changes in plasma protein and albumin concentrations indicated that there was a loss of globulin from the vascular volume in both conditions and an addition of albumin to the plasma in 50 RPM. The difference in plasma albumin dynamics was possibly related to an effect of pedal speed on movement of fluid in the lymphatic vessels of the legs. PMID- 3342787 TI - Control of heat-induced cutaneous vasodilatation in relation to age. AB - Well matched unacclimatised older (age 55-68, 4 women, 2 men) and younger (age 19 30, 4 women, 2 men) subjects performed 75 min cycle exercise (approximately 40% VO2max) in a hot environment (37 degrees C, 60% rh). Rectal temperature (Tre), mean skin temperature (Tsk), arm blood flow (ABF, strain gauge plethysmography), and cardiac output (Q, CO2 rebreathing) were measured to examine age-related differences in heat-induced vasodilatation. Tre and Tsk rose to the same extent in each group during the exposure. There was no significant intergroup difference in sweat rate (older: 332 +/- 43 ml.m-2.h-1, younger: 435 +/- 49 ml.m-2.h-1; mean +/- SEM). However, the older subjects responded to exercise in the heat with a lower ABF response which could be attributed to a lower Q for the same exercise intensity. The slope of the ABF-Tre relationship was attenuated in the older subjects (9.3 +/- 1.3 vs 17.9 +/- 3.3 ml.100 ml-1.min-1.degrees C-1, p less than 0.05), but the Tre threshold for vasodilatation was about 37.0 degrees C for both groups. These results suggest an altered control of skin vasodilatation during exercise in the heat in older individuals. This attenuated ABF response appears to be unrelated to VO2max, and may reflect an age-related change in thermoregulatory cardiovascular function. PMID- 3342788 TI - Alteration of period and amplitude of circadian rhythms in shift workers. With special reference to temperature, right and left hand grip strength. AB - 48 male shift workers in various industries volunteered to document circadian rhythms in sleeping and working, oral temperature, grip strength of both hands, peak expiratory flow and heart rate. All physiological variables were self measured 4 to 5 times a day for 2 to 4 weeks. Individual time series were analyzed according to several statistical methods (power spectrum, cosinor, chi squares, ANOVA, correlation, etc.) in order to estimate rhythm parameters such as circadian period (tau) and amplitude (A), and to evaluate subgroup differences with regard to tolerance to shift work, age, duration of shift work, speed of rotation and type of industry. The present study confirms for oral temperature and extends to other variables (grip strength of both hands, heart rate) that intolerance to shift work is frequently associated with both internal desynchronization and small circadian amplitude. The internal desynchronization among several circadian rhythms supports the hypothesis that these latter are driven by several oscillators. Many differences were observed between circadian rhythms in right and left hand grip strength: circadian tau in oral temperature was correlated with that in the grip strength of the dominant hand but not with that of the other hand; changes in tau s of the non-dominant hand were age related but did not correlate with temperature tau; only the circadian A of the non-dominant hand was associated with a desynchronization. Thus, circadian rhythms in oral temperature and dominant hand grip strength may be driven by the same oscillator while that of the non-dominant hand may be governed by a different one. Internal desynchronization between both hand grip rhythms as well as desynchronization of performance rhythms reported by others provide indirect evidence that circadian oscillator(s) may be located in the human cerebral cortex. PMID- 3342789 TI - Maximal oxygen uptake in Chilean workers of normal nutritional status. AB - Maximum oxygen uptake (VO2max) was measured directly and predicted from cardiac frequency measurements in 54 healthy Chilean industrial workers aged 20 to 55 years, together with assessment of their dietary intake, body composition and blood chemistry. Measurement of VO2 was performed on a motor-driven treadmill. The predicted VO2max was obtained using a cycle ergometer by two methods: 1) the Astrand-Ryhming nomogram and 2) the linear relationship between "steady state" heart rate (HR) and submaximum work, with subsequent extrapolation to "maximum" heart rate. Extrapolation of the HR/load regression line to 170 bpm permitted determination of the physical working capacity at 170 bpm (W170). VO2max for the 20-29 year group (Group I) averaged 3624 ml.min-1 and decreased to 3066 ml.min-1 in the 50-55 year group (Group IV). Lower values were obtained using the Astrand Ryhming nomogram and HR/load regression (-15% and -9% respectively). W170 was also affected by age (Group I: 190.6 W and Group IV: 158.5 W). No significant correlation were found between VO2max and plasma variables, with the exception of cholesterol (r = 0.59). On the contrary, anthropometric variables showed significant correlations with VO2max, which permitted the prediction of VO2max using multiple regression equations. The two best correlations were: 1. VO2max = 0.800 - 0.0225.(A) +0.0189.(W)+1.26.(H) (r = 0.87; p less than 0.001) 2. VO2max = 0.996 - 0.0176.(A) + 0.025.(W) + 0.838.(H) + 0.0255.(LBM) (r = 0.88; p less than 0.001) where A = years of age; W = body weight in kg; H = height in m and LBM = lean body mass in kg. PMID- 3342790 TI - The influence of muscle interstitial volume on K+-induced heart rate drive in rats. AB - During exercise heart rate is influenced by reflexogenic drives which are elicited by receptors situated in the interstitial space. Since the structure of interstitial tissue is complex (e.g. fixed negative charges of glycosaminoglycans), the situation in the immediate surrounding of the receptors might differ from the free fluid phases of blood or lymph in which the concentrations of stimulating substances are usually determined. Physiological variations of the interstitial structure may be due to changes in interstitial volume induced by exercise or the hydrostatic effects on body fluids. The objective of the present study was to investigate the effect of the interstitial volume on the relationship between heart rate and K+ stimuli applied through the muscle blood vessels. The calves of 12 male Wistar rats were artificially perfused and separated from the rest of the body with the sciatic nerve remaining intact. In these preparations the heart rate (HR) responses to low (4 mM) and high (8 mM) potassium concentrations were determined at different interstitial volumes. Expansion of the interstitial volume was obtained by reducing the colloid-osmotic pressure of the perfusate. The combination of intracellular oedema and mechanical limitation of total volume expansion (tapeing) was utilized to decrease the interstitial volume. When switching between the low and high potassium concentrations, significant heart rate responses could be observed only with reduced interstitial volume. It is suggested that the interstitial structure surrounding the muscular receptors modifies the relationship between heart rate response and the K+ stimuli determined in blood or lymph. PMID- 3342791 TI - Force of knee extensor and flexor muscles and cross-sectional area determined by nuclear magnetic resonance imaging. AB - The maximal strengths of knee extensor (E) and flexor (F) muscles were compared in a group of 6 male subjects aged 24-31 years. Cross-sectional area (CSA) of E and F was evaluated from planimetric measurements of Nuclear Magnetic Resonance (NMR) imaging axial scans, carried out at five levels along the thigh. Maximal CSA for E was found at 2/3 upper femur height and at 1/3 lower femur height for F. Maximum isometric force (MIF) of E was found to be 135% greater than that of F. The maximum CSA of E was found to be 93% larger than CSA of F. The calculated mechanical advantage of the flexors was estimated to be 13.8% higher than that of the knee extensors (0.116 +/- 0.012 and 0.132 +/- 0.005, respectively). However, when MIF of E and F were standardised for their respective CSA, no significant difference was found between their stress: 80.1 +/- 15.5 N.cm-2 for E and 70.5 +/ 7.0 N.cm-2 for F. From the present study, it is concluded that no significant difference exists between the maximum stress of knee extensor and flexor muscles despite large differences in their absolute values of force and CSA and that the NMR imaging technique enables accurate in-vivo determination of the CSA of individual muscles. PMID- 3342792 TI - Effect of lower-body positive pressure on postural fluid shifts in men. AB - To quantify the effect of 60 mm Hg lower-body positive pressure (LBPP) on orthostatic blood-volume shifts, the mass densities (+/- 0.1 g.1-1) of antecubital venous blood and plasma were measured in five men (27-42 years) during combined tilt table/antigravity suit inflation and deflation experiments. The densities of erythrocytes, whole-body blood, and of the shifted fluid were computed and the magnitude of fluid and protein shifts were calculated during head-up tilt (60 degrees) with and without application of LBPP. During 30-min head-up tilt with LBPP, blood density (BD) and plasma density (PD) increased by 1.6 +/- 0.3 g.1-1, and by 0.8 +/- 0.2 g.1-1 (+/- SD) (N = 9), respectively. In the subsequent period of tilt without LBPP, BD and PD increased further to + 3.6 +/- 0.9 g.1-1, and to + 2.0 +/- 0.7 g.1-1 (N = 7), compared to supine control. The density increases in both periods were significant (p less than 0.05). Erythrocyte density remained unaltered with changes in body position and pressure suit inflation/deflation. Calculated shifted-fluid densities (FD) during tilt with LBPP (1006.0 +/- 1.1 g.1-1, N = 9), and for subsequent tilt after deflation (1002.8 +/- 4.1 g.1-1, N = 7) were different from each other (p less than 0.03). The plasma volume decreased by 6.0 +/- 1.2% in the tilt-LBPP period, and by an additional 6.4 +/- 2.7% of the supine control level in the subsequent postdeflation tilt period. The corresponding blood volume changes were 3.7 +/- 0.7% (p less than 0.01), and 3.5 +/- 2.1% (p less than 0.05), respectively. Thus, about half of the postural hemo-concentration occurring during passive head-up tilt was prevented by application of 60 mm Hg LBPP. PMID- 3342794 TI - Supramaximal test results of male and female speed skaters with particular reference to methodological problems. AB - Six male and six female elite speed skaters were tested during two bicycle ergometer tests: a 30 s sprint test and a 2.5 min supra maximal test. During the 2.5 min test oxygen consumption was measured every 30 s. The males showed 30-31% higher mean power output values both during the sprint test (1103 versus 769 Watt) and during the 2.5 min test (570 versus 390 Watt). Maximal oxygen consumption was 31% higher for the males than for the females (5.10 versus 3.50 1.min-1). However, when expressed per kilogram lean body weight (LBM), power output and oxygen consumption was equal for both sexes. Differences between present and previous results are most likely due to methodological problems with the estimation of load during the supra maximal test. Subjects appear to experience difficulties in distributing their power output over the 2.5 min if they are tested for the first time. For experienced skaters and cyclists, fixed levels of 19 W.kgLBM-1 as initial load setting for the sprint test and 8 W.kg LBM 1 for the 2.5 min test are recommended. PMID- 3342793 TI - The effects of arm crank training on the physiological responses to submaximal wheelchair ergometry. AB - The purpose of this investigation was to examine the cardiovascular and metabolic effects of a 5 wk arm crank (AC) training program on submaximal wheelchair (WC) ergometry in able-bodied women. The 6 subjects in the training group (TG) and 4 in the control group (CG) performed a 10 min WC exercise prior to and following the training period at a power output (PO) that elicited 70% of the pre-training peak oxygen uptake (VO2). Steady state VO2, heart rate (HR), cardiac output (Qc) and stroke volume (Vs) were measured. Resting and post-exercise blood lactate concentrations (LA) were measured, the difference was recorded as net LA. The TG exercised on the AC 3 d.wk-1 at a PO that elicited 85% of each subject's recorded peak HR. Each session consisted of four 4 min exercise bouts preceded by a 2 min warm-up and interspersed with 2 min rest periods. After training, the TG had a significantly (p less than 0.05) lower HR, larger Vs and lower LA in response to the WC exercise. Qc and VO2 were not significantly altered. The results demonstrate that the AC exercise program used in this study produced a physiological training effect which was observed during submaximal WC exercise of an intensity frequently encountered during daily WC ambulation. It appears that short-term, moderate intensity AC training offers an adequate stimulus to reduce the stress imposed by wheelchair locomotion. PMID- 3342795 TI - Serum creatine kinase and lactate dehydrogenase changes following an eighty kilometer race. Relationship to lipid peroxidation. AB - Pre and post race serum malondialdehyde (MDA), creatine kinase (CK) and lactate dehydrogenase (LDH) levels were studied in runners following an 80 km (50 mile) race. MDA is an indicator of lipid peroxidation. Subjects averaged 47.4 years (range 35-60), had a mean maximal oxygen uptake (VO2max) of 48.2 ml/kg, and averaged 121 km (75 miles) per week in training. Throughout the race, runners maintained a pace approximating 72% of VO2max. Previous data from our laboratory indicated a high correlation between resting MDA and total CK and CK-MB. Present resting data confirms prior results (r = 0.84 and 0.69 respectively). In addition, the relationship established at rest persisted following exercise (r = 0.62 and 0.85 respectively). Post race CK, CK-MB, LDH and MDA values for all subjects were significantly greater than resting values (p less than 0.01). Mean post CK and CK-MB levels were nearly 10 and 4 times lower, respectively, than prior values from our laboratory in subjects following a 100 km (62 mile) race. It was concluded that post exercise serum enzyme elevations, universally accepted as a marker of tissue damage, correlate well and may be related to an exercise induced lipid peroxidation. PMID- 3342797 TI - Simple and complex carbohydrate-rich diets and muscle glycogen content of marathon runners. AB - The effects of simple-carbohydrate (CHO)- and complex-CHO-rich diets on skeletal muscle glycogen content were compared. Twenty male marathon runners were divided into four equal groups with reference to dietary consumption: depletion/simple, depletion/complex, nondepletion/simple, and nondepletion/complex. Subjects consumed either a low-CHO (15% energy [E] intake), or a mixed diet (50% CHO) for 3 days, immediately followed by a high-CHO diet (70% E intake) predominant in either simple-CHO or in complex-CHO (85% of total CHO intake) for another 3 days. Skeletal muscle biopsies and venous blood samples were obtained one day prior to the start of the low-CHO diet or mixed diet (PRE), and then again one day after the completion of the high-CHO diet (POST). The samples were analysed for skeletal muscle glycogen, serum free fatty acids (FFA), insulin, and lactate and blood glucose. Skeletal muscle glycogen content increased significantly (p less than 0.05) only in the nondepletion/simple group. When groups were combined, according to the type of CHO ingested and/or utilization of a depletion diet, significant increases were observed in glycogen content. Serum FFA decreased significantly (p less than 0.05) for the nondepletion/complex group only, while serum insulin, blood glucose, and serum lactate were not altered. It is concluded that significant increases in skeletal muscle glycogen content can be achieved with a diet high in simple-CHO or complex-CHO, with or without initial consumption of a low-CHO diet. PMID- 3342796 TI - Influence of muscle dimensions on economy of isometric exercise in rat medial gastrocnemius muscles in situ. AB - The effect of muscle dimensions on economy (force-time integral divided by the amount of energy utilized) was investigated in male rats (body mass range 95-490 g), anaesthetized with pentobarbital. The medial gastrocnemius muscle in situ performed 6 maximal isometric contractions of 350 ms duration (1.s-1) at twitch optimum length at 35 degrees C. The areas under the 6 time-force curves were added to obtain force-time integral of the experiment. Differences of concentrations of ATP, phosphocreatine and lactate between experimental and contralateral (resting) muscles were used to calculate high-energy phosphate consumption due to stimulation. Muscle mass and cross-sectional area increased (approximately +400% and +300%, respectively) over the rat body mass range studied. Muscle length and length of the most distal fibre bundle increased by approximately 17 mm and 4 mm, respectively. Force-time integral (N.s) increased proportional to cross-sectional area whereas high-energy phosphate consumption (mumoles) increased proportional to muscle mass. The relative fraction of the total energy consumption utilized for force-independent processes was independent of rat body mass. The economy of the actomyosin system was unaffected during growth, whereas economy of the whole muscle decreased during growth by approximately 30% (p less than 0.001). The effect of muscle dimensions on economy is discussed with respect to human endurance capacity measured by voluntary isometric contractions. PMID- 3342799 TI - Interaction between exercise training and cold acclimation in rats. AB - Five groups of 10 rats were used. Group A included sedentary rats kept at 24 degrees C, group B exercised-trained rats and group C rats exposed at -15 degrees C for 2 h every day and kept at 24 degrees C for the remaining time. These 3 groups were kept on this regimen for 10 weeks. In addition group D was acclimated to cold (2 h.d-1 at -15 degrees C) for 6 weeks and subsequently deacclimated at 24 degrees C for 4 weeks. Group E was also acclimated to cold for 6 weeks and during the deacclimation, at 24 degrees C period which lasted 4 weeks, the animals were exercised 2 h per day. Following the 10 week experimental period all animals were sacrificed and DNA and protein content of the IBAT as well as its total mass were measured. The results show significant increases in the cold adapted group. Exercise training which had no effect on brown adipose tissue IBAT at room temperature, caused an accelerated reduction in weight, DNA and protein content of the BAT in rats previously acclimated to cold. In spite of this, the thermogenic response to noradrenaline was significantly enhanced in the group which exercised during the deacclimation period. It is suggested that tissues other than IBAT may explain this enhanced heat production capacity. PMID- 3342798 TI - Physical versus pharmacological counter-measures. Studies on febrile rabbits. AB - 128 experiments were carried out on febrile rabbits at air temperatures of 8, 18, 24 and 30 degrees C in order to analyze the thermoregulatory effects and mechanisms of physical and/or pharmacological counter-measures. Fever was achieved by injection of 0.1 micrograms Salmonella typhi endotoxin (LPS)/kg into an ear vein. As the pharmacological counter-measure, injections of acetylsalicylic acid (ASA) into an ear vein were chosen. For the physical counter measure, cooling thermodes (5 degrees C) were constructed for the abdominal skin, for the ear and for the rectum. ASA injections had no effect on the first fever maximum, even if applied 20 to 60 min before the LPS injection, but eliminated the second fever maximum. Of course, the additional hyperthermia observed at 30 degrees C ambient temperature could not be eliminated by the injections. On the other hand, cooling procedures can obviously not affect the pyrogen-induced temperature increase, but reduce the hyperthermic effect of a higher ambient temperature. Rectal cooling was more effective than ear or abdominal skin cooling. Abdominal cooling evoked an increase in metabolic heat production. Application of combined physical and pharmacological counter-measures achieved the strongest and quickest reduction of the second maximum, whereas the first maximum was not affected, as in all other experiments. The study emphasizes the necessity of taking into account the time course of the effector mechanisms in order to discriminate between hyperthermic and febrile components of temperature increase. In the initial phase cooling measures would evoke unwanted regulatory responses of the effectors, whereas during the second febrile maximum they would achieve a quicker reduction of core temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342801 TI - Blood groups and transitional cell carcinoma of the upper urinary tract. AB - A retrospective analysis of the blood groups of 74 patients with transitional cell carcinoma of the upper urinary tract is presented. The blood group distribution of the patients reflected that of the general population. No relationship was found between blood groups and stage and grade of the tumour or patient survival. Nor were blood groups predictive of bladder tumour recurrence and stump recurrence in patients who had undergone simple nephrectomy. PMID- 3342800 TI - Initial cardiovascular response on change of posture from squatting to standing. AB - The immediate cardiovascular responses on active change from the squatting (control) to the standing position differ from those obtained in the lying-to standing manoeuvre. Without exception, the first beat after changing from squatting to standing showed a decrease in systolic, diastolic and mean pressure by 2.0 +/- 1.1 kPa (14.6 +/- 8.3 mm Hg), 1.4 +/- 1.7 kPa (10.6 +/- 12.6 mm Hg) and 1.9 +/- 1.0 kPa (13.9 +/- 7.3 mm Hg), respectively. During the 4th or 5th pulse after standing the pulse pressure was significantly higher than when lying (P less than 0.01). Mean pressure reached a minimum of 7.7 +/- 1.9 kPa (57.8 +/- 14.4 mm Hg) after 7.1 +/- 1.1 s. Thereafter the blood pressure increased to a new level within about 15 s. 11 of 16 subjects demonstrated a biphasic heart rate (HR) response. The maximum HR was reached after 11.0 +/- 2.4 s of standing. In all experiments, the peaks in HR were distinctly delayed after the blood pressure dips. We conclude that an arterial baroreflex could be implicated in the immediate HR increase after a squatting-to-standing manoeuvre. The subsequent time course of the initial HR response, however, might be induced by other mechanisms. PMID- 3342802 TI - Fiber-optic versus microtip transducers in simultaneous urethrocystometry. A comparative study. AB - A comparative study of a new fiber-optic transducer versus a microtip transducer was performed in 13 females. A good correlation was found on bladder pressure. The urethral pressure diverged considerably, as the pressures measured with the fiber-optic transducer were about two thirds of the pressures found with the microtip. The functional urethral length measured with the fiber-optic transducer was also shorter. PMID- 3342803 TI - Antireflux procedure by Lich-Gregoir. Indications and results. AB - Reflux is not the cause of the ascension of microorganisms into the urinary bladder, yet it enables bacteria to reach the kidney and fosters pyelonephritis, persistent infections and nephropathy with all its consequences. The efficiency of the Lich-Gregoir antireflux procedure has to be judged by its results. The criterium of operative success in 190 renal units (146 children) is the positive influence on renal growth and physical development by controlling pyelonephritis and eliminating recurrent supravesical infections in more than 98% of the operated children. PMID- 3342805 TI - Construction of ileal nipples as anti-reflux valve technique. AB - When an ileal loop is used to replace the ureter or to create a urinary pouch, an adequate anti-reflux mechanism is essential. Intussusception of the ileal wall can be used but a proper technique must be chosen to prevent necrosis of the nipple. Good knowledge of the vascularization of the ileal wall is necessary. Leaving a 1-cm strip of mesenterium when stripping it from the ileal wall provides adequate circulation. Nipples of 3 cm or longer are enough to create an anti-reflux mechanism. PMID- 3342804 TI - Bilateral single ureteral ectopia. AB - We report 11 cases of bilateral single ectopic ureter. The clinical features and surgical management are discussed. With current surgical techniques, these patients can be treated successfully. PMID- 3342806 TI - Superoxide dismutase activity in renal cell carcinoma. AB - Both Cu-Zn- and Mn-superoxide dismutase (SOD) activities were determined in renal cell carcinoma and tumor-uninvolved renal tissues in 25 patients with renal cancer. These enzymatic activities were similar in tumor and tumor-uninvolved renal tissues. The age of the patients, grade or stage of tumors had no apparent effect on SOD activities. Renal arterial embolization caused a slight decrease (p less than 0.05) in Cu-Zn-SOD activity in tumor tissues, but none in other enzymes in the same tissues, while renal arterial embolization reduced each SOD activity in tumor-uninvolved renal tissues (p less than 0.01 - p less than 0.001). Therefore the development of renal cell carcinoma is probably not related to the abnormality of renal SOD, but renal ischemic changes appear to lower each SOD activity in normal renal tissues. PMID- 3342807 TI - Endocrine effects of oestrogen withdrawal in long-term treated patients with prostatic adenocarcinoma. AB - Eighteen patients with prostatic adenocarcinoma, treated with oestrogen for 45 months or more, were followed-up after withdrawal of oestrogen treatment. Serum concentrations of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol-17 beta, testosterone-oestradiol-binding globulin (TeBg) and prolactin were measured at different intervals between 3 and 42 months after cessation of treatment. Serum testosterone concentrations after cessation of oestrogen treatment were low (range 71.4 +/- 6.3 to 120.8 +/- 23.7 nmol/100ml), whereas the concentrations of LH (range 21.8 +/- 3.6 to 32.6 +/- 9.1 U/1) and FSH (range 31.2 +/- 5.5 to 54.7 +/- 9.5 U/1) were within or higher than the reference range. Prolactin (range 6.0 +/- 85.3 to 7.9 +/- 68.2 micrograms/1) was within the reference range. No significant changes in serum concentrations of testosterone, LH, FSH and prolactin occurred during the follow-up period. The serum concentrations of both oestradiol-17 beta and TeBg, found between 13 and 36 months after oestrogen cessation (range 43.8 +/- 4.6 to 46.2 +/- 5.9 and 64.0 +/- 2.5 to 86.0 +/- 10.0, respectively) were significantly lower than the concentrations found between 3 and 12 months (range 71.9 +/- 10.4 to 99.8 +/- 12.9 and 124.1 +/- 15.5 to 140.2 +/- 13.7, respectively). It is concluded that in patients with prostatic adenocarcinoma, long-term oestrogen treatment causes an irreversible impairment of Leydig cell function and consequently a reduced testosterone secretion after cessation of oestrogen treatment. PMID- 3342808 TI - Common characteristics of primary cell cultures originated from invasive urothelial carcinoma. AB - Ten primary cultures from invasive urothelial carcinomas were studied by light and electron microscopy. In all cultures, cells with accumulations of glycosaminoglycans were observed. Long membrane extensions with accumulations of glycosaminoglycans invaded neighboring cells and formed an extracellular matrix as well. The extracellular matrix inhibited cell proliferation and enhanced tumor nodule formation. PMID- 3342810 TI - Manufacture and clinical employment of an antibiotic silicon-rubber catheter. AB - In order to present or minimize the frequent occurrence of urinary infection and other complications following indwelling catheterization, we devised a drug releasing silicon catheter. Attached to its tip is an appliance which has a honeycomb pattern with many spaces into which antibiotic particles are inserted. In our series, 28 patients suffering from various conditions were treated accordingly with very gratifying results. Kanamycin is found to be the antibiotic of choice which can be slowly but constantly released when coming into contact with the urine. Following treatment the concentration of kanamycin in urine could be maintained at a level of 25-100 micrograms/ml of urine for a period of 20-24 days, much higher than the therapeutic value of 20 micrograms/ml of urine. PMID- 3342809 TI - Morphological and immunohistochemical characteristics of a cell line originated from noninvasive human bladder transitional-cell carcinoma. AB - A cell line (IG) was derived from a noninvasive transitional cell carcinoma grade II. The cells were propagated in vitro for 9 months, had a low proliferative capacity, formed tumor nodules, and showed four characteristic morphological stages. Primary epithelial-like cells were characterized as stage I; fibroblast like cells with loss of contact inhibition of growth as stage II; fibroblast-like cells with long cytoplasmic projections, massive glycosaminoglycan content and tumor nodule formation as stage III; and, as stage IV, granulated stellate cells. The cell culture progressed cytologically from well-differentiated stage I to less-differentiated stage IV. The four stages were confirmed and examined by electron microscopy. Immunoreactivity for fibronectin, keratin, epithelial membrane antigen and carcinoembryonic antigen shown by the cell line and the tissue indicates that the cell line represents the original cell population in the tumor. Glycosaminoglycan production by these cells was found to be responsible for the formation of tumor nodules which appeared in culture at the same time as the patient had developed an invasive bladder tumor. Glycosaminoglycans were observed as a massive accumulation intracellularly and extracellularly, as rods or thick slices in layers of adherent vesicles and granules covering the cell culture. Normal bladder epithelial cells and fibroblasts grew in monolayer, showed contact inhibition of growth, were devoid of intracellularly accumulated glycosaminoglycans and produced uniform extracellular matrix different from that of IG cells. PMID- 3342811 TI - Ileal conduit hemorrhage. AB - Recurrent severe episodes of hemorrhage from an ileal urinary conduit occurred in the presence of unilateral obstructive urographic nonfunction and a poorly characterized coagulopathy. Features relevant to this patient and to the problem in general are reviewed. PMID- 3342812 TI - Multiple cavernous hemangioma of the kidney. AB - A case of renal angiomas, located on the tip of the papillae, presented with severe hematuria which required several blood transfusions. Radiological studies including arteriography were negative. The diagnosis was confirmed by intraoperative nephroscopy and histology. PMID- 3342813 TI - No more noses to the glass. PMID- 3342815 TI - Legal influence and educational policy in special education. PMID- 3342814 TI - Perspectives on eligibility for and placement in special education programs. PMID- 3342816 TI - Tolerance and technology of instruction: implications for special education reform. PMID- 3342817 TI - Minority MMR overrepresentation and special education reform. PMID- 3342818 TI - Putting the individual into aptitude-treatment interaction. PMID- 3342820 TI - Integrated classroom versus resource model: academic viability and effectiveness. PMID- 3342821 TI - Deaf children's acquisition of prereading skills using the reciprocal teaching procedure. PMID- 3342819 TI - Effects of strategy training on metamemory among learning disabled students. PMID- 3342822 TI - The attraction of color for active attention-problem children. PMID- 3342823 TI - Means and ends. PMID- 3342824 TI - Who leaves and who stays in special education: a 2-year follow-up study. PMID- 3342825 TI - The consulting teacher model: risks and opportunities. PMID- 3342826 TI - Peer interactions in mainstreamed and specialized classrooms: a comparative analysis. PMID- 3342828 TI - Observed supervisory behavior and teacher burnout in special education. PMID- 3342827 TI - Impact of Diana, Larry P., and P.L. 94-142 on minority students. PMID- 3342830 TI - Budding of choriocapillary endothelial cells in the normal pigmented rat. PMID- 3342829 TI - Retinal dystrophy in Wistar-Furth rats. AB - A form of retinal degeneration in the Wistar-Furth strain of rat is described. The changes observed was classified as either mild or severe, depending on the severity of the dystrophy seen by light and electron microscopy. In the mild stage, there was a slight decrease in the number of photoreceptor nuclei in the outer nuclear layer (ONL) and there were pyknotic nuclei in the inner nuclear layer. A few photoreceptor outer and inner segments showed focal swellings. The basal infoldings of the retinal pigment epithelium (RPE) were distributed irregularly, creating spaces that contained collagen-like fibrils. However, the interepithelial tight junctions remained impermeable to intravenously injected peroxidase. In severely dystrophic retinas, there was a further decrease in the width of the ONL, and the photoreceptor outer and inner segments were degenerated. In extreme cases, the photoreceptor cell disappeared completely and the inner retina abutted the RPE. Further changes were also noted in the basal membrane of the RPE; in some regions the membrane was totally flat while in others it formed exaggerated infoldings. In addition, the RPE was frequently vascularized by vessels that originated from the retina. The endothelium of those intra-RPE vessels located near Bruch's membrane was frequently fenestrated. Alterations also occurred in the retinal capillaries; some were degenerated, while others showed increased tortuosity or focal thickenings of the basal lamina. In addition, there were focal increases in the amount of stroma between Bruch's membrane and the choriocapillaris. PMID- 3342831 TI - Synthesis of glycoconjugates by trabecular meshwork of glaucomatous corneoscleral explants. PMID- 3342833 TI - An experimental technique to study the turnover of concentrated hyaluronan in the anterior chamber of the rabbit. AB - An experimental technique to study the turnover of hyaluronan in the anterior chamber in single animals has been developed. It is based on the fact that circulating hyaluronan labelled with tritium in the acetyl group is rapidly taken up by the liver and degraded to tritiated water. 3H-labelled hyaluronan was mixed with high concentration, high molecular weight hyaluronan (Healon) and injected into the anterior chamber of rabbits. The concentration of tritiated water in blood plasma was followed for up to 13 days. An initial rise of radioactivity in the blood was followed by an exponential decrease. From the exponential disappearance it was possible to calculate the rate of turnover of water in the body. This was used to correct the initial rise of tritium for water losses. After this correction the appearance of radioactive water in blood corresponded to the disappearance of hyaluronan from the eye plus a 45 min time-lag due to the catabolism in the liver. Using this technique it was found that trace amounts of radioactive hyaluronan and 0.055 ml and 0.2 ml of 1% hyaluronan exhibited half lives in the anterior chamber of 1.5, 7 and 13 hr respectively. When the same technique was used for subcutaneously and intramuscularly injected hyaluronan half-lives of 50 and 30 hr, respectively, were recorded. PMID- 3342832 TI - Effect of light deprivation on the ERG responses of taurine-deficient rats. AB - The decrease of taurine levels in the retina of taurine-depleted rats treated with guanidinoethane sulfonate (GES) reduced the amplitude of the a- and b-waves of the electroretinogram, registered as a function of the log relative intensity stimulus. The effect was observed either in rats exposed to a light-darkness cycle or to continuous darkness; this effect was somewhat more pronounced in retinas of rats exposed to light. Values obtained from the Naka-Rushton equation for the V-log I curve for the a-wave showed that the half-saturating intensity was unchanged but Vmax was decreased by GES treatment. Implicit times for the b wave delayed whereas those for the a-wave were unaffected by the treatment. PMID- 3342834 TI - Relative effectiveness of prodrug and viscous solution approaches in maximizing the ratio of ocular to systemic absorption of topically applied timolol. AB - The effectiveness of the prodrug approach in maximizing the ratio of ocular to systemic absorption of topically applied timolol was compared with that based on viscous solutions. The pigmented rabbit was the experimental animal. o-Butyryl timolol, a lipophilic ester prodrug of timolol, was found to be twice as effective as hyaluronic acid and poly(vinyl alcohol) solutions in enhancing the ocular absorption of timolol. In addition, it was slightly more effective than retaining the instilled dose in the conjunctival sac for 240 min via nasolacrimal blockade. On the other hand, due to its inability to minimize contact of the instilled dose with the nasal mucosa, o-butyryl timolol was less capable than the viscous solutions in reducing systemic drug absorption. But this could be corrected by reducing the instilled solution volume from 25- to 5 microliter, resulting in a nine-fold reduction in plasma timolol levels while still providing the same amount of drug in the aqueous humor as a five times higher dose of timolol. The net result was a 15-fold improvement in the ratio of ocular to systemic drug absorption, which was also achieved upon retaining the instilled dose in the conjunctival sac for 240 min. It thus appears that the approach based on improved corneal absorption would be as effective as that based on improved retention in the conjunctival sac in maximizing the ratio of ocular to systemic drug absorption, so long as a smaller instilled dose volume of the prodrug is used. PMID- 3342836 TI - Effects of chronic diphenylhydantoin on cerebral metabolism in the adult rat. AB - Diphenylhydantoin is one of the most widely used anticonvulsant agents in humans. To examine its effects on brain metabolism, we used the quantitative autoradiographic [14C]deoxyglucose method to measure local cerebral glucose utilization in adult rats receiving 50 mg/kg/day diphenylhydantoin for 1 week. Thirty-three brain structures were analyzed to determine whether the drug has global or site-specific effects on cerebral metabolism. Chronic administration produced statistically significant decreases in 23 neocortical and subcortical structures compared with those in vehicle-injected control animals. Therefore, our data support the concept that diphenylhydantoin has widespread depressant effects on brain metabolism. PMID- 3342835 TI - Heterogeneity of gamma-crystallins from spiny dogfish (Squalus acanthias) eye lens. AB - Mammalian lenses contain multiple gamma-crystallin gene products, which are differentially synthesized during lens development. We now report the isolation and characterization of multiple gamma-crystallins from lenses of adult spiny dogfish (Squalus acanthias) aged about 20-30 years. About 50% of total lens protein solubilized in 50 mM phosphate, pH 7.0; about 25% of this soluble fraction consists of gamma-crystallins as determined by gel filtration. These gamma-crystallins appear homogeneous with respect to molecular weight (approximately equal to 20,000) on SDS-polyacrylamide gels, but their isoelectric points range from below pH 6 to above 10. Preparative cation-exchange chromatography on SP-Sephadex at pH 4.8 resolves four major subfractions, while anion-exchange on DEAE-cellulose at pH 9.5 resolves seven subfractions. Although these procedures separate basic from acidic polypeptides, most of these gamma crystallin subfractions still consist of polypeptide mixtures, as determined by ion-exchange HPLC and isoelectric focusing. Analytical cation-exchange HPLC on SynChropak CM300 at pH 6.0 resolves at least 10 different gamma-crystallin components. Amino acid compositions of all the subfractions are similar, yet distinct in the sense that three subclasses can be distinguished. Sulfhydryl residues range from three to six per chain, most of which are buried. The large heterogeneity of gamma-crystallins in adult lens may result from different gene products in combination with post-translational modification. PMID- 3342837 TI - An ontogenic study of amygdala seizures induced by penicillin in rats. AB - Amygdaloid seizures were induced by unilateral injection of penicillin into the amygdala in infant and young rats to investigate the ontogenic development of the amygdaloid seizure. "Repetitive isolated discharges" and "sustained high frequency discharges" appeared in 3- to 4-day-old rats. In these rats, the repetitive discharges appeared in bilateral subcortical structures simultaneously with those of the amygdaloid penicillin focus, but sustained high-frequency discharges were localized to the ipsilateral subcortical structures. In 9- to 10 day-old and 14- to 15-day-old rats, repetitive discharges occurred simultaneously in the bilateral cortices and subcortical structures. In contrast to them, sustained high-frequency discharges propagated faster from the amygdala penicillin focus to the bilateral midbrain reticular formation and medial nucleus of the thalamus than to other regions. In 20- to 21-day-old and older rats, both events occurred simultaneously at all cerebral sites. These results indicate that the subcortical structures, especially the midbrain reticular formation and medial nucleus of the thalamus, play an important role in seizure propagation from the ipsilateral to the contralateral hemisphere in infant rats. PMID- 3342838 TI - Projections from upper cervical inspiratory neurons to thoracic and lumbar expiratory motor nuclei in the cat. AB - Previous studies have demonstrated the existence of axonal projections from propriospinal respiratory neurons in the rostral cervical cord of the cat (upper cervical inspiratory neurons) to the vicinity of the phrenic and rostral thoracic inspiratory (external) intercostal motoneurons. However, no synaptic targets of the upper cervical inspiratory neurons have been identified. This study investigated the axonal projections to the caudal thoracic and upper lumbar cord and the possible existence of inhibitory connections to the expiratory intercostal and abdominal motoneurons. The connections from upper cervical inspiratory neurons to expiratory motoneurons in the lower thoracic cord were examined using the methods of antidromic mapping and the spike-triggered averaging of intracellular potentials. Of the 70 upper cervical inspiratory neurons examined, only four (5.7%) could not be antidromically activated from the T9 segment of the spinal cord. The axons of 66 upper cervical inspiratory antidromic activation at less than 5 microV, and the presence of collaterals was confirmed by antidromic mapping in 30 cases (49.2%). Of 21 axons tested for lumbar projections, 13 (61.9%) projected as far as T12, seven (33.3%) as far as L1, three (14.3%) as far as L2, and one (4.8%) was antidromically activated from L3. Spike-triggered averaging of the synaptic potentials recorded intracellularly from expiratory intercostal motoneurons in T9 and T10 spinal segments was done for 27 upper cervical inspiratory neurons, 17 of these with 4 or more motoneurons, for a total of 111 expiratory motoneurons. In 16 cases the motoneurons were injected with Cl- to reverse IPSPs and the spike-triggered averaging was repeated. No monosynaptic or disynaptic post-synaptic potentials were seen in any of the spike-triggered averages. We concluded that the upper cervical inspiratory neurons may provide inspiratory inhibition to expiratory motoneurons via a di- or oligosynaptic pathway involving segmental inhibitory interneurons and that either the spike-triggered averaging technique was not sensitive enough to detect the ipsilateral connections or the interneuron pathway was to the contralateral side of the spinal cord. PMID- 3342839 TI - Blood-spinal cord barrier disruption proximal to a spinal cord transection in the rat: time course and pathways associated with protein leakage. AB - The effects of spinal cord transection on the blood-spinal cord barrier of the rat were examined at the ultrastructural level at sites 0.5 and 1.0 cm proximal to the injury. Using the vascular tracer horseradish peroxidase (HRP), the time course and pathways of barrier disruption were evaluated. At 0.5 cm, barrier disruption was noted from as early as 15 min and continued to 12 h after injury, whereas at 1.0 cm, evidence for vascular permeability was confined to between 15 min and 3 h. The presence of barrier breakdown to exogenous protein at a distance from the transection emphasizes that injury promotes a more generalized vascular response which likely contributes to subsequent edematous changes. The mechanism(s) involved in increased permeability appears to be primarily related to transendothelial vesicular transport of the tracer. There was no evidence for interendothelial leakage of the tracer across compromised tight junctions. In comparing these findings with those reported on sites distal to a transection, it is clear that there is an asymmetry in the vascular response to HRP. The pinocytotic index, an indicator of endothelial uptake of HRP, was significantly elevated (compared with control) distal to a transection from 3 h through 3 days after injury, attaining a maximum at 12 h. In contrast, the pinocytotic index proximal to a transection was significantly elevated compared to control values at only 1 h after injury. Furthermore, at 3 h after injury, when barrier disruption was most prominent, there was a smaller percentage of vessels exhibiting leakage to HRP proximal as opposed to distal to a transection. PMID- 3342840 TI - Unilateral interruption of geniculate and callosal inputs to the visual cortex of cats: ocular dominance and responsiveness of cells in the deafferented and in the intact hemispheres. AB - In order to study the ocular dominance and responsiveness of cells in the deafferented visual cortex, the geniculate and the callosal inputs were interrupted in adult cats by either simultaneous (OTCCX) or separate surgical transection of the optic tract (OTX) and the posterior corpus callosum (CCX). Unit recording was chronically carried out mainly in the boundary of areas 17-18, the callosal projection zone. A small proportion of visually responsive cells was encountered in the deafferented hemisphere of the OTCCX (8.3%) and the OTX (6.3%) cats. In the intact hemisphere, 59.7% of the cells were visually responsive in the OTCCX cats and 57.0% in the OTX cats; they were 61.6% of the cells in the CCX cats and 85.6% in the normal controls (both hemispheres). The majority of the cells in the deafferented hemisphere of the OTCCX (88.9%) and the OTX (82.4%) cats were binocularly driven. In the intact hemisphere of the OTCCX cats, 85.1% of the cells were binocularly driven, in comparison to 77.6% in the OTX cats, 48.8% in the CCX cats, and 81.5% in the normal controls. We therefore concluded that following unilateral elimination of the geniculate input as well as the callosal transection, binocularity in the intact hemisphere was preserved despite the remarkable diminution in the responsiveness level there. Furthermore, the supply of visual input to the deafferented hemisphere was not affected after callosotomy, suggesting an alternative transfer, albeit minor, via an anterior callosal or another commissural pathway. PMID- 3342841 TI - Participation of the serotonin2 receptor in the iminodipropionitrile-induced dyskinetic syndrome. AB - The effects of the specific serotonin2 antagonist ketanserin on the persistent lateral head shakes, vertical neck dyskinesia, and the random circling behaviors induced by iminodipropionitrile were evaluated. Ketanserin inhibited all these aspects of the behavioral syndrome at all doses tested. These results add further evidence for the involvement of the serotonin system in some of the components of the iminodipropionitrile-induced dyskinetic syndrome. PMID- 3342842 TI - Attenuation of progressive brain hypoperfusion following experimental subarachnoid hemorrhage by large intravenous doses of methylprednisolone. AB - Experimental subarachnoid hemorrhage was produced in chloralose-anesthetized cats by slow injection of 0.5 ml/kg autologous arterial blood into the cisterna magna. As a result, there was an initial (within 5 min) 25.1% decrease in caudate nuclear blood flow as measured by hydrogen clearance. Between 5 min and 3 h postinjection, there was a further and progressive 25.9% decline in caudate blood flow. The hemorrhage also caused a slow increase in intracranial pressure, a decrease in cerebral perfusion pressure, and an increase in caudate vascular resistance. In contrast, the administration of a single 30 mg/kg i.v. dose of methylprednisolone sodium succinate 30 min after the acute hemorrhage resulted in stabilization of caudate blood flow and vascular resistance and some restoration of those parameters toward prehemorrhage values. This effect was not correlated with a decrease in intracranial pressure or an increase in cerebral perfusion pressure. A 15 mg/kg i.v. dose of the drug had only a slight effect on caudate blood flow. A 60 mg/kg i.v. dose, while initially supportive, lost its effect during the later stages of the experiment, indicating a sharp biphasic dose response relationship for the effect of methylprednisolone on caudate blood flow after subarachnoid hemorrhage. However, of the three doses, only 60 mg/kg significantly decreased the slow posthemorrhage rise in intracranial pressure. The beneficial effect of the 30 mg/kg i.v. dose of the drug on caudate blood flow, separate from an effect on the slow rise in intracranial pressure, suggests that the steroid support of caudate perfusion is due to a direct protective effect of the drug on the microvasculature. Based on previous studies showing an identical dose-response pattern for the ability of methylprednisolone to prevent posttraumatic lipid peroxidation of central nervous system tissue and progressive ischemia development, the possibility of the drug's inhibition of hemorrhage initiated vasoconstrictor prostanoid action and microvascular lipid peroxidation is proposed. PMID- 3342843 TI - Regional blood flow in resting and stimulated sciatic nerve of diabetic rats. AB - The role of ischemia in the pathogenesis of diabetic peripheral neuropathy remains uncertain. We used the distribution of [14C]butanol to measure resting regional sciatic nerve blood flow in normal, anesthetized rats and in rats with acute experimental diabetes from streptozotocin administration. Regional flows in hind limb biceps femoris muscle and skin were simultaneously measured. In additional diabetic rats, these blood flows were compared in both limbs after proximal electrical stimulation of one sciatic trunk (10 shocks/s) for 15 min. One month after streptozotocin administration, 8 of 11 test rats were hyperglycemic. Resting nerve blood flow in the hyperglycemic rats--5.6 +/- 3.07 ml.min-1.100 g-1--was significantly less than that in the controls (9.4 +/- 3.9 ml.min-1.100 g-1, P = 0.002). Muscle blood flow was normal and skin blood flow decreased in these rats. Calculated tissue vascular resistances were elevated in all three tissues. Stimulation of one sciatic trunk in five other diabetic rats resulted in a stimulated nerve blood flow of 15.7 +/- 7.7 ml.min-1.100 g-1, and nerve blood flow in the resting control limb was 7.7 +/- 4.3 ml.min-1.100 g-1 (P = 0.009). Muscle blood flow increased approximately fourfold on the stimulated side but skin blood flow did not increase. Resting sciatic nerve blood flow is modestly decreased in acute streptozotocin-induced diabetes, but the neural blood vessels are still responsive to the increase in nerve metabolic activity associated with nerve stimulation. PMID- 3342844 TI - Aging and presbycusis: effects on 2-deoxy-D-glucose uptake in the mouse auditory brain stem in quiet. AB - Autoradiography was used to assess the incorporation of [2-14C]deoxy-D-glucose by the auditory brain stem of young and aging mice of the C57BL/6 strain (which demonstrates progressive chronic sensorineural hearing loss) and the CBA strain (which maintains good hearing until late in life). Animals were injected with labeled 2-deoxyglucose and placed in quiet for 45 min; brain stem sections were prepared for autoradiography. The amounts of 2-deoxyglucose incorporated into the anterior ventral cochlear nucleus (AVCN), inferior colliculus (IC), and trigeminal nerve (TN) were densitometrically analyzed. Within each subject, the densities of the three structures were statistically compared. In every mouse, inferior colliculus density was greater than that of the anterior ventral cochlear nucleus, which was greater than trigeminal nerve density. To compare subject groups, relative densities (inferior colliculus and anterior ventral cochlear nucleus re: trigeminal nerve) were used; no significant differences were found between groups. Thus, aging, with or without severe loss of hearing, is not associated with altered incorporation of 2-deoxyglucose (and presumably glucose) in quiet. PMID- 3342845 TI - A two-compartment modification of the silicone chamber model for nerve regeneration. AB - In the nerve regeneration silicone chamber model, the regenerate which forms across a 10-mm gap between proximal and distal nerve stumps is a monofascicular structure with an outer perineurial-like cell sheath. Recent work has provided indications that the geometry of the regenerate within a silicone chamber can be altered by experimental modifications of the chamber matrix. In the present study we modified the standard silicone chamber into a two-compartment chamber by inserting a 6- or 10-mm-long siliconized nitrocellulose strip in order to obtain two separate regenerates. Light microscopy 16 days after implantation revealed that two separate nerve structures had formed, one on each side of the nitrocellulose partition and adjacent to it, and each with its own perineurial like cell sheath. In chambers with 6-mm-long strips a monofascicular regenerate started from the proximal stump and divided into two separate structures as it approached the proximal end of the strip: the two fascicles joined again into a monofascicular structure in the distal portion of the chambers. The new two compartment silicone chamber model appears suitable for future examinations of experimental fasciculation. In addition, the nitrocellulose partition should allow one to study specific effects of growth factors on axonal regeneration in vivo, as growth factors bind strongly to untreated nitrocellulose while retaining their biological activity. PMID- 3342846 TI - Effects of a hybrid maternal environment on brain growth and corpus callosum defects of inbred BALB/c mice: a study using ovarian grafting. AB - The corpus callosum of many but not all BALB/c mice is either abnormally small or absent. The basis for the defect is hereditary, but the proportion of mice expressing the anomaly can be modified by changing the early environment. The present study investigated the effects of an F1 hybrid maternal environment, which is known to promote better fetal development than an inbred environment, on body and brain growth in BALB/c and on the incidence of the corpus callosal defect. Ovarian follicle cells from BALB/cWah (albino) mice were grafted into pigmented F1 hybrid, BALB/cWah, and pigmented BALB female hosts of comparable age which were subsequently mated to BALB/cWah males. Groups of unoperated BALB/cWah and pigmented BALB dams were included as controls. Data from 111 litters were analyzed. Results showed that BALB mice with F1 mothers had heavier bodies at birth, weaning, and 100 days of age and heavier brains at 100 days than those with either grafted or ungrafted BALB mothers. The effects at birth were evident across all litter sizes (2 to 11), but those at weaning and 100 days were seen only in litters of more than 5 or 6. Neither the F1 hybrid maternal environment nor the grafting procedure itself appeared to influence the incidence or expression of the corpus callosal defect. About 22% of the offspring from each of the three groups (ungrafted BALB, grafted BALB, and grafted F1) showed a defective corpus callosum. PMID- 3342847 TI - Changes in serum and striatal free amino acids after Venezuelan equine encephalomyelitis virus infection. AB - The infection with the Venezuelan equine encephalomyelitis virus produced a significant increase in the concentration of alanine, arginine, asparagine, glutamine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and valine in the striatum of rats. On the contrary, the concentrations of aspartate, GABA, glutamate, and taurine were reduced. Arginine, aspartate, glycine, methionine, phenylalanine, taurine, and tyrosine concentrations were increased in the serum of infected rats. However, the modifications in the content of free amino acids in the striatum and serum of rats that survived the infection were qualitatively and quantitatively different from those detected during the acute phase of the infection. PMID- 3342848 TI - Axonal growth in mesothelial chambers: effects of a proximal preconditioning lesion and/or predegeneration of the distal nerve stump. AB - Preformed, autologous mesothelial chambers were utilized to study axonal growth following selective predegeneration of the distal nerve stump and/or preconditioning of the proximal nerve stump. The left and/or right sciatic nerve of rats was exposed and transected in the thigh. Two weeks after transection, the left proximal nerve stump was cross-anastomosed with the right distal nerve stump by using a mesothelial chamber leaving a 15-mm gap between the two nerve stumps. Previous studies have shown that axonal overgrowth normally does not occur over this gap distance to the distal stump. Three months after cross-anastomosing, regeneration across the 15-mm gap was evaluated by muscle action potential recordings and light microscopical examination. In experiments in which a distal nerve stump was selectively degenerated and the proximal segment was freshly cut, axons had bridged the 15-mm gap in six of seven rats. When a proximal preconditioned nerve stump was matched with a freshly cut distal stump, axonal overgrowth occurred in only 4 of 10 experiments. In experiments including a proximal preconditioned nerve stump and a distal predegenerated stump, axons bridged the gap in 6 of 8 experiments. We concluded that a priming lesion, including manipulation with proximal and/or distal stump, enhances axonal growth in mesothelial chambers. PMID- 3342849 TI - Sleep deprivation increases thalamocortical excitability in the somatomotor pathway, especially during seizure-prone sleep or awakening states in feline seizure models. AB - Pathological somatomotor system excitability and generalized seizures occur throughout the sleep-awake cycle but peak at different times in the amygdala kindling and systemic penicillin epilepsy models. Sleep loss increases seizure activity in both models during all waking and sleep states but does not alter the timing of seizure susceptibility in the sleep-wake cycle. Although the mechanism for sleep-deprivation seizures is unknown, we propose that sleep loss magnifies somatomotor system hyperexcitability patterns in all states, thereby increasing seizure vulnerability at all times but preferentially during seizure-prone intervals. To evaluate this hypothesis, the timing of ventral lateral thalamic and motor cortex excitability, indexed by amplitudes of primary evoked responses, was studied throughout the sleep-wake cycle in eight cats before and after nearly total sleep deprivation. Sleep loss was induced by 24-h exposure to a modified "flower pot" procedure; the control procedure consisted of 24-h exposure to a larger pedestal which did not affect sleep time. Findings confirmed the hypothesis, as follows: (i) Sleep deprivation increased ventral lateral thalamic and motor cortical excitability nonspecifically. (ii) Motor cortex hyperexcitability correlated best with penicillin seizure activity; both were elevated in slow-wave sleep and drowsiness after awakening from slow-wave sleep before sleep loss and were further increased by sleep loss. (iii) Ventral lateral thalamic hyperexcitability patterns correlated best with the timing of kindled seizure susceptibility; both peaked during transitions from slow-wave to REM sleep before and after sleep loss but were maximal after sleep loss. (iv) Sleep loss increased thalamocortical excitability and seizure susceptibility during stable REM sleep in both models, but values were lower than in other states. These results suggest a chronic neuropathology at different levels of the neuraxis for dissimilar epilepsy models and upon which the sleep-waking state modulation of seizures is superimposed. Sleep deprivation may aggravate seizures in both models by nonspecific enhancement of thalamic and cortical excitability. PMID- 3342850 TI - Excitant amino acids and audiogenic seizures in the genetically epilepsy-prone rat. I. Afferent seizure initiation pathway. AB - The afferent pathway involved in initiation of audiogenic seizures in the genetically epilepsy-prone rat was investigated by bilateral microinfusion of the excitant amino acid antagonist 2-amino-7-phosphonoheptanoate into the major brain stem and subcortical nuclei of the auditory system. This antagonist has been shown to possess anticonvulsant properties in other seizure models, and an excitant amino acid has been implicated as a putative neurotransmitter in several of these nuclei. Seizure severity was significantly reduced following infusion of this agent into the cochlear nucleus, superior olivary complex, inferior colliculus, and medial geniculate body. Many of these animals exhibited a complete blockade of seizures. The smallest effective dose in the cochlear nucleus and the medial geniculate body was 5 nmol per side. The smallest effective dose in the olive was 1 nmol, and in the inferior colliculus 0.1 nmol per side was protective. The onset of anticonvulsant effectiveness was earliest in the inferior colliculus. These findings showed that the inferior colliculus was the most sensitive auditory center to the anticonvulsant action of 2-amino-7 phosphonoheptanoate and that imbalance between inhibitory and excitatory transmission within this brain structure may be crucial in the initiation of audiogenic seizures in the genetically epilepsy-prone rat. PMID- 3342851 TI - Excitant amino acids and audiogenic seizures in the genetically epilepsy-prone rat. II. Efferent seizure propagating pathway. AB - Previous studies indicate that the inferior colliculus is the brain stem auditory nucleus most sensitive to the chemical blockade of audiogenic seizures in the genetically epilepsy-prone rat. Other auditory structures do not appear to be as important. This study attempted to define the efferent pathways involved in propagation of the seizure from the colliculus to the spinal cord where the motor components of the convulsion are generated. This study also determined whether certain nuclei which have been implicated in the propagation of seizures in other epilepsy models are involved in audiogenic seizures. The excitant amino acid antagonist, 2-amino-7-phosphonoheptanoate, was infused bilaterally into several of those sites. The drug was effective in significantly reducing seizure severity with infusion of 5 nmol bilaterally into the midbrain and the pontine reticular formation or the substantia nigra. However, similar drug doses were not effective when infused into the entopeduncular nucleus even though prominent behavioral effects were observed with this infusion. Infusion of 2-amino-7 phosphonoheptanoate into the prepiriform cortex resulted in a small but significant reduction in seizure severity. These results suggest that inhibition of excitatory transmission within the substantia nigra and the reticular formation effectively blocks the output pathway for the audiogenic seizures, whereas the role of the prepiriform cortex in this process is relatively minor. PMID- 3342852 TI - A stable, selective electrode for recording single motor-unit potentials in humans. AB - A new application of electrode technology has enabled recording of single motor unit potentials in human first dorsal interosseus muscle with more versatility than has been traditionally associated with this paradigm. The design, manufacture, and application are detailed for an electrode which has been used to discriminate potentials during efforts up to maximal voluntary contraction. The electrode comprises a branched, bipolar configuration which is positioned subcutaneously over the belly of the muscle. This extramuscular location maximizes stability and, with appropriate orientation of the electrode relative to the architecture of the muscle, ensures adequate selectivity of single motor unit potentials. PMID- 3342853 TI - A blind trial of silicone chamber fluid in nerve regeneration in the rat. AB - The nerve growth-promoting effects of the fluid accumulating in vivo from 1 to 28 days within silicone chambers were tested on the sciatic nerves of rats. We measured the elongation of sensory axons following nerve transection repaired by means of fibrin sealant allowing local application of the fluid. We found no difference between transections treated with chamber fluid and controls. PMID- 3342854 TI - Cerebral hypoxia-ischemia in immature rats: methodological considerations. AB - We used a model of perinatal hypoxic/ischemic brain damage which combines unilateral common carotid artery ligation and hypoxia (8% O2). Protein synthesis inhibition and cell loss were found in the ipsilateral forebrain of 11-day-old rats when hypoxia was initiated 4 h but not 24 h after carotid ligation. [14C]Iodoantipyrine uptake studies suggest that compensating vascular changes which protect the ipsilateral forebrain occur within 24 h of carotid ligation. PMID- 3342855 TI - Fine distribution of gamma-aminobutyric acid, glutamic acid decarboxylase, and glutamic acid in the rabbit cerebellum. AB - The fine distribution of GABA, glutamic acid decarboxylase, and glutamic acid within each layer of the rabbit cerebellar cortex was determined with microanalytical methods. The greatest glutamic acid decarboxylase activity and the highest GABA concentration were found in the Purkinje cell layer. In the distribution of GABA and glutamic acid decarboxylase the peak of glutamic acid decarboxylase activity was more pronounced than that of GABA; the concentration of glutamic acid did not show much variation between each layer. PMID- 3342856 TI - 20th Annual Meeting of the Swiss Societies for Experimental Biology (USGEB/USSBE). March 10/11, 1988, Interlaken. Abstracts. PMID- 3342857 TI - Reference values: relevant controls for clinical decision-making. PMID- 3342858 TI - Myelokathexis associated with multiple congenital malformations: immunological study on phagocytic cells and lymphocytes. AB - A 5-year-old boy was first seen at the age of 11 months when he presented with growth retardation, skeletal dysmorphisms and neutropenia. Since then he has remained leukopenic except when he has pulmonary infections with a marked leukocytosis. Despite his neutropenia, marked myeloid hyperplasia was evident on marrow smear examination; many cells showed abnormally hypersegmented nuclei, with unusual shape or pyknotic nuclei. Phagocytic cells showed impaired phagocytosis, candidacidal activity, metabolic burst and chemotaxis. Moreover, the patient's serum generated less chemotactic activity than normal serum. These data indicate a selectively complex defect of the neutrophil during differentiation associated with the presence of an inhibitor of chemotactic factors in the patient's serum. PMID- 3342859 TI - Age-related differences and circadian and seasonal variations of myelopoietic progenitor cell (CFU-GM) numbers in mice. AB - The effect of aging on the myelopoietic progenitor cell (CFU-GM) numbers in mice was studied with special emphasis on biological rhythms in hemopoiesis. Female C3H mice, 16-, 21- and 26-month-old, were investigated versus 3-month-old controls every 3 hours during the 24-h period at three different times of the year. Strong circadian rhythms were observed in both CFU-GM concentration and content in the femur of all age-groups. The amplitudes and the 24-h mean values were declining in mice aged 21 and 26 months. From 16 months of age, a significant advance of circadian peak phases was observed. The overlapping was variable during the 24-h period. The present results may explain previous inconsistencies regarding myelopoietic progenitor cell numbers in aging mice. Some seasonal differences in rhythmicity patterns were also observed. Fitting of original data to single sinus functions was highly significant, although important details sometimes were obscured. PMID- 3342860 TI - Platelet volume and intraplatelet adenine nucleotides in various hematologic disorders. AB - By recent advanced techniques, blood platelets have proved to be varied in size and metabolism in various hematologic disorders. We examined platelet volume and intraplatelet adenine nucleotides in 36 patients with various hematologic disorders in order to clarify the quantitative platelet abnormalities. Platelet volumes were smaller in patients with acute leukemia and aplastic anemia, and larger in patients with immune thrombocytopenic purpura (ITP). The amount of intraplatelet ADP was decreased and ATP/ADP ratio was increased in acute leukemia, aplastic anemia and myeloproliferative disorders (MPD), which strongly suggested the presence of storage pool deficiency in these patients. Intraplatelet ADP per volume was decreased in acute leukemia, aplastic anemia and MPD, and ATP per volume was decreased in aplastic anemia. ATP content was increased in ITP in proportion to the increased platelet volume. These parameters were examined in 36 patients with the following hematologic disorders: 7 acute leukemia treated with cytotoxic chemotherapy, 5 aplastic anemia, 3 paroxysmal nocturnal hemoglobinuria (PNH), 9 immune thrombocytopenic purpura (ITP), 5 hypersplenism and 7 myeloproliferative disorders (MPD). PMID- 3342861 TI - Correlation between plasma levels of selenium and antithrombin-III. AB - Patients with previous myocardial infarction were tested for antithrombin-III (AT III) activity and selenium levels in their plasma and compared with sex- and age matched healthy control individuals. Patients and controls showed a positive correlation between AT-III and selenium levels (r = 0.27, p = 0.015). After calculatory adjustment for this correlation, selenium was found to be significantly negatively correlated with disease. Multivariate analysis of differences between patients and controls indicated that triglyceride levels in serum had the greatest discriminatory ability (r2 = 0.169), followed by AT-III (r2 = 0.072) and selenium (r2 = 0.056). The increased AT-III levels were correlated with the use of warfarin and beta blockers in the patients, but these drugs could not explain the comparatively low selenium levels in the patients. Serum total cholesterol and plasma fatty acid composition had no discriminatory power in multivariate testing. The various fatty acid did not show co-variation with the selenium levels. The clinical significance of these observations is not clear, but they are consistent with the hypothesis that selenium is an important determinant in cardiovascular disease. The relation between AT-III and selenium should be further evaluated. PMID- 3342862 TI - EF Bart's disease: interaction of the abnormal alpha- and beta-globin genes. AB - EF Bart's disease is an uncommon form of thalassaemia intermedia resulting from the co-inheritance of alpha-thalassaemia and haemoglobin E in the same subject. Starch-gel electrophoresis revealed two phenotypes in 19 patients with EF Bart's. 16 patients had Hbs CS + E + F + Bart's and the remainder had Hbs E + F + Bart's. DNA mapping and haemoglobin electrophoresis indicated that there are four genotypes, involving 5 abnormal globin genes, responsible for this thalassaemia syndrome. PMID- 3342863 TI - Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin concentrations in anaemic subjects. AB - Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin were determined on 2 successive days in 48 patients with anaemia. The correlation coefficients between the paired determinations were 0.86, 0.89, 0.95 and 0.95, and the day-to-day coefficients of variation (in per cent) were 33, 11, 12 and 13 for serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin, respectively. Thus, in patients with anaemia, day-to-day variations in serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin are at least as high as in healthy controls. The results indicate important limitations in the use, particularly, of serum iron in the clinical investigation of anaemia. PMID- 3342864 TI - Haematopoiesis in the aged as studied by in vitro colony assay. AB - Changes occurring in human haematopoiesis with advancing age were studied using an in vitro haematopoietic colony assay in 22 elderly subjects with unexplained anaemia, and in 15 elderly and 15 young subjects without anaemia. Both elderly groups were found to have significantly lower numbers of bone marrow early erythroid-committed progenitors (BFU-E) than the young controls. The elderly anaemic group also showed significantly lower numbers of granulocyte/macrophage progenitors (CFU-GM) than the young controls. However, the responses of the erythroid-committed progenitors in the elderly groups to erythropoietin and burst promoting activity were similar to those observed in the young controls. Therefore, it is probable that anaemia tends to occur easily in elderly individuals as a result of reduction of reserves of haematopoietic progenitors with advancing age. PMID- 3342865 TI - Methimazole-induced agranulocytosis: growth inhibition of myeloid progenitor cells by the patient's serum. AB - The mechanism for agranulocytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune-mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole-induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune-mediated mechanism for methimazole-induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells. PMID- 3342866 TI - Changes in myosin heavy chain stoichiometry in pig tracheal smooth muscle during development. AB - The stoichiometry of the myosin heavy chains (MHCs) has been measured in the tracheal smooth muscle of the pig after electrophoresis on SDS 4% polyacrylamide gel. The ratio of slower migrating MHC to the faster migrating MHC was 2.1 neonates, 1.5 in young and 0.95 in old pigs (P less than 0.01) showing that MHC composition changes with development. The unequal proportion of MHCs was not compatible with a heterodimeric arrangement of the MHCs in the native molecule as proposed earlier by Rovner et al. [(1986) Am. J. Physiol. 250, C861-870] and it is suggested that native molecules may be composed of homodimer heavy chains. PMID- 3342867 TI - Presence and characteristics of epidermal growth factor receptors in human fetal small intestine and colon. AB - In the present study, we demonstrate for the first time the presence of important concentrations of EGF binding sites in isolated epithelial cells of both human fetal small intestine and colon as early as 12 weeks gestation. The pattern of EGF binding in the small intestine between 12 and 17 weeks show that binding was significantly higher (2.5-fold) in younger fetuses than in older fetuses. Moreover, the fetal colon exhibited a much higher binding capacity (1.5-2.5 times) than corresponding intestinal cells for all age groups studied. Analysis of Scatchard representations reveal that the concentration of high- and low affinity binding sites in colonic epithelial cells are twice the values observed in corresponding intestinal cells. The present data raise interesting possibilities as to the role of this growth factor in human fetal gut development. PMID- 3342868 TI - Nicotinic acetylcholine receptor: a structural model for alpha-subunit peptide 188-201, the putative binding site for cholinergic agents. AB - A peptide corresponding to amino acid sequence 188-201 of the alpha-subunit of Torpedo AChR binds alpha-Bgtx. The S-S bridge between Cys 192 and 193 is essential for the binding as Tyr in position 189. The same sequence 188-201 corresponding to human AChR, which instead of Tyr has a Thr in position 189, binds alpha-Bgtx with a much lower efficiency. Monoclonal antibodies raised against Torpedo peptide 188-201 recognize Torpedo AChR and antibodies against Torpedo AChR recognize peptide 188-201 indicating that the synthetic peptide and the corresponding sequence in the native molecule share some immunological epitopes. With computer graphics and energy refinement a molecular model of this peptide has been elaborated. PMID- 3342869 TI - Iodinated melatonin mimics melatonin action and reveals discrete binding sites in fetal brain. AB - Iodinated melatonin was used to study melatonin sites of action in brain. Iodomelatonin mimicked the effects of melatonin on reproductive development in Djungarian hamster fetuses. 125I-melatonin injected into the dam was recovered from fetal brain. In vitro autoradiographic studies revealed a remarkably discrete distribution of competitive 125I-melatonin-binding sites in the fetal brain, with binding in median eminence/arcuate nucleus area greater than suprachiasmatic nucleus greater than pineal gland much greater than anterior pituitary gland much greater than preoptic area. 125I-melatonin promises to be a useful tool for understanding the sites and mechanism of action of melatonin. PMID- 3342870 TI - Active center differences between cathepsins L and B: the S1 binding region. AB - The substrate peptide bond cleaved by cathepsins B and L is determined not by the amino acid contributing the carboxyl group to this bond as in the case of serine proteases but rather by the presence of a neighboring amino acid with a large hydrophobic side chain. From a study of the inhibitory potency in a series, Cbz Phe-X-CHN2, in which Phe promotes binding at S2 (terminology of [(1968) Biochem. Biophys. Res. Commun. 32, 898-902]) while the amino acid X probes S1, it is shown that this region of cathepsin L also has the ability to accommodate large hydrophobic side chains. In this respect cathepsin L differs from cathepsin B. Thus Cbz-Phe-Tyr(O-t-Bu)CHN2 inactivates cathepsin L with a rate 2.5 x 10(4) greater than that for cathepsin B. PMID- 3342871 TI - Monoclonal antibody to human endothelial cell surface internalization and liposome delivery in cell culture. AB - A monoclonal antibody (mAb), E25, is described that binds to the surface of cultured human endothelial cells. Upon binding E25 is rapidly internalized and digested intracellularly. Selective liposome targeting to the surface of the cells is performed using a biotinylated E25 antibody and an avidin-biotin system. Up to 30% of the cell-adherent liposomal lipid is internalized. PMID- 3342873 TI - The primary structure of human platelet profilin: reinvestigation of the calf spleen profilin sequence. AB - The primary structure of human platelet profilin was determined by aligning the sequences of its tryptic peptides to the previously determined calf spleen profilin sequence [(1979) FEBS Lett. 101, 161-165]. Comparison of the peptide fingerprints of the two proteins suggested a higher homology than that found by direct sequence comparison. We therefore reinvestigated the sequences of the peptides from calf spleen profilin. We identified four incorrect charge assignments and a deletion of three residues. The similarity between the two vertebrate profilins amounts to 95%. PMID- 3342872 TI - Fibronectin isoforms in plasma membrane domains of normal and regenerating rat liver. AB - Plasma membrane fractions were obtained from the three surface domains of normal and regenerating adult rat livers. It was shown by immunoblotting that sinusoidal plasma membranes contained the characteristic 220 and 210 kDa fibronectin doublet, whereas bile canalicular plasma membranes contained a 220 kDa component. In lateral plasma membranes, 180, 190 and 220 kDa fibronectin isoforms were present. Fibronectin in the sinusoidal and canalicular plasma membranes was shown, by detergent/aqueous phase partitioning, to be more hydrophilic than isoforms in lateral plasma membranes. Changes in the distribution of fibronectin between plasma membrane domains occurred during liver regeneration and their significance, especially in relation to cell division, is discussed. PMID- 3342874 TI - A new pathway for phosphatidylserine synthesis in rat liver microsomes. AB - It has been shown that the phosphate moiety of glycerophosphate is incorporated into phosphatidylserine of rat liver microsomes, but not of mitochondria. The reaction is dependent on CMP. This observation suggests that the new pathway of acyl-specific synthesis of phosphatidylserine proposed by J.P. Infante [(1984) FEBS Lett. 170, 1-14] can proceed in rat liver microsomes. PMID- 3342875 TI - Phospholipid peroxidation as a factor in gallstone pathogenesis. AB - Phospholipid peroxidation markedly reduces the stability of mixed micellar systems composed of cholate, phosphatidylcholine and supersaturating levels of cholesterol. This suggests that lipid peroxidation is likely to play a significant role in the precipitation of cholesterol from gallbladder bile, thus in the pathogenesis of cholesterol gallstones. This conclusion is supported by studies of the nucleation time of cholesterol in gallbladder biles, which was significantly reduced by exposure to a stream of oxygen. This effect of phospholipid peroxidation on cholesterol solubility may occur in other biological fluids as well. In view of the increased lipid peroxidation in the elderly, it may explain the effect of age on the frequency of various diseases related to cholesterol precipitation. PMID- 3342876 TI - Selective decrease in low-Mr HMG proteins HMG I and HMG Y during differentiation of mouse teratocarcinoma cells. AB - We have studied the presence of high-mobility-group (HMG) chromatin proteins in undifferentiated F9 mouse teratocarcinoma cells and F9 cells, which were induced to differentiate by treatment with retinoic acid and dibutyryl-cAMP for 5 days. Acetic acid/urea-polyacrylamide gel electrophoresis and reversed-phase HPLC revealed that the induced F9 cells contained 77 and 62% less HMG I and HMG Y, respectively, than their untreated counterparts. The relative amounts of two other low-Mr HMG proteins HMG 14 and HMG 17 remained essentially unchanged and only a minor decrease was observed in the content of one of the high-Mr HMG proteins, HMG 2. The identity of the low-Mr HMG proteins was verified by amino acid analysis or partial sequencing. These results suggest that HMG I and HMG Y are HMG proteins specific for undifferentiated cells. PMID- 3342877 TI - Detection and microsequencing of juvenile hormone-binding proteins of an insect by the use of an iodinated juvenile hormone analog. AB - An [125I]iodinated juvenile hormone (JH) analog can be used as a sensitive and highly selective probe for the visualization of high-affinity, (JH)-specific binding proteins from insect hemolymph samples. The proteins can be detected in their native form using a two-dimensional (isoelectric focusing then native gradipore gel) separation of the crude protein mixture containing the 125I labeled iodinated JH analog. The proteins can be transferred to activated glass fiber paper by electroblotting, and the location of the bound gamma-emitter can be found by exposure of the dried gel or the electroblot to X-ray film. The radiolabeled protein spot can be excised from the Coomassie-stained glass fiber paper and subjected directly to gas-phase N-terminal amino acid sequencing. This non-destructive, non-denaturing technique may have wide applicability in identifying and sequencing ligand-specific binding proteins in complex mixtures. PMID- 3342878 TI - The effect of phosphate on the unfolding-refolding of phosphoglycerate kinase induced by guanidine hydrochloride. AB - Phosphate ions were found to stabilize the native structure of phosphoglycerate kinase without modifying the folding pathway. The transition curves obtained from different signals: enzyme activity, ellipticity at 220 nm and fluorescence intensity at 336 nm (excitation at 292 nm) are shifted to smaller guanidine hydrochloride cm values in the absence of phosphate. The kinetic characteristics are qualitatively similar, unfolding rate constants being slightly smaller in the presence of phosphate. The mechanism by which the native structure of phosphoglycerate kinase is stabilized by phosphate probably occurs upon specific phosphate binding to the nucleotide beta- or gamma-phosphate binding site of nucleotides. PMID- 3342879 TI - 5-Aminolevulinic acid formation from glutamate via the C5 pathway in Clostridium thermoaceticum. AB - A cell-free extract of the anaerobic eubacterium, Clostridium thermoaceticum, catalyzes the synthesis of 5-aminolevulinic acid (ALA) from glutamate via the C5 pathway. The enzyme reaction resembles that of higher plants and algae in cofactor requirements and sensitivity to ribonuclease. From the phylogenetic distribution it is proposed that the C5 pathway evolved earlier than the ALA synthase pathway. PMID- 3342880 TI - Cell attachment and fibrinogen binding properties of platelet and endothelial cell thrombospondin are not affected by structural differences in the 70 and 18 kDa protease-resistant domains. AB - Structural differences between platelet and endothelial cell thrombospondin (TBSP) were found in two protease-resistant domains (70 and 18 kDa). The 70 kDa fragment is involved in the binding of TBSP to fibrinogen and the 18 kDa fragment in the attachment to various cultured cells. Despite these structural differences, platelet and endothelial cell TBSP bound with the same affinity to fibrinogen and mediated the attachment of smooth muscle cells but not of endothelial cells. PMID- 3342881 TI - Complementary addressed modification of double-stranded DNA within a ternary complex. AB - Double-stranded DNA containing a d(pG)18.d(pC)18 sequence was shown to be selectively alkylated in the vicinity of this fragment using the 5'-p-(N-2 chloroethyl-N-methylamino)benzylamide of deoxyribooligocytidylate, CIRCH2NH(pdC)n (n = 9,15), in conditions favouring triple-stranded complex formation. PMID- 3342882 TI - High levels of protein carboxyl methyltransferase in well-differentiated human endometrial carcinoma. AB - The levels of protein carboxyl methyltransferase, an enzyme that methylates free carboxyl groups of proteins, were determined in normal human proliferative and secretory endometrium and in poorly and well-differentiated endometrial carcinoma. Protein carboxyl methyltransferase activity was 67% higher in the well differentiated carcinoma than in the normal tissues, while similar enzyme levels were observed in the two normal tissues and in the poorly differentiated carcinoma. The results suggest that in the well-differentiated tumor there is excessive protein methylation and offer a possible biochemical probe for distinguishing between the two types of tumor. PMID- 3342884 TI - Cloning and sequencing of cDNA that encodes goat growth hormone. AB - The cDNA that encodes goat growth hormone (gGH) was isolated from a goat pituitary cDNA library. The cDNA, about 880 base pairs long, had a coding sequence, 5'- and 3'-untranslated regions and a poly(A) chain. The cDNA could encode a polypeptide of 217 amino acids. The amino acid sequence homology between gGH and the sequences of bovine GH, rat GH and human GH was 99, 83 and 66%, respectively. By Northern blot hybridization, we found that the possible gGH gene is transcribed in the goat pituitary. PMID- 3342883 TI - Radioligand binding of antagonists of platelet-activating factor to intact human platelets. AB - Two new antagonists of platelet-activating factor (PAF), the pyrrolothiazole derivative 52770 RP and the triazolodiazepine WEB 2086, have been studied as radioligands in intact human platelets. [3H]52770 RP and [3H]WEB 2086 bound specifically to high-affinity sites with dissociation constants (Kd) of 14.8 and 6.1 nM, respectively. The maximal number of sites for [3H]52770 RP binding was approx. 15-fold higher than for [3H]PAF and [3H]WEB 2086. In addition, C16-PAF, lyso-PAF, WEB 2086 and 52770 RP had Ki values which were nearly identical for both [3H]PAF and [3H]WEB 2086, whereas only 52770 RP competed for [3H]52770 RP binding sites. These results demonstrate that in human platelets the sites of [3H]WEB 2086 binding are identical to [3H]PAF-binding sites, whereas those of [3H]52770 RP are not. [3H]WEB 2086 appears, therefore, to be a suitable antagonist radioligand for labelling PAF receptors. PMID- 3342885 TI - Genotyping of human class I alcohol dehydrogenase. Analysis of enzymatically amplified DNA with allele-specific oligonucleotides. AB - Large inter-individual differences are noted in the susceptibility to alcohol related problems. Part of this variation may be due to the different isoenzyme patterns of the alcohol-metabolizing enzymes and, consequently, different pharmacokinetics of alcohol degradation. We have used the polymerase chain reaction and oligonucleotide hybridization to amplify and analyze class I alcohol dehydrogenase isoenzyme-specific genomic DNA. The method unambiguously distinguishes between different allelic variants and thus provides a new means of elucidating the alcohol dehydrogenase isoenzyme pattern of humans. PMID- 3342886 TI - A resonance Raman study of the binding of ethanol and methanol to ferrihemoglobin. AB - The interactions of ethanol and methanol with ferrihemoglobin were examined using resonance Raman spectroscopy. After binding either alcohol, the low-frequency resonance Raman spectra of human ferrihemoglobin are almost identical to the unperturbed spectrum except for shifts in the 309 cm-1 band to higher frequency by as much as 8 cm-1. The ethanol-induced shift is greater than that with methanol even though complex formation was less for ethanol than methanol. The spectral changes imply a site-specific, similar binding of these alcohols to ferrihemoglobin which may involve steric interactions. Possible assignments of the 309 cm-1 band to structural features as well as potential mechanisms of the alcohol-induced spectral changes are discussed. PMID- 3342887 TI - Asparaginyl-rhamnose: a novel type of protein-carbohydrate linkage in a eubacterial surface-layer glycoprotein. AB - The subunits of the crystalline surface layer of Bacillus stearothermophilus, strain NRS 2004/3a contain carbohydrates covalently linked to protein. Hydrolysis of a glycopeptide obtained by pronase digestion of the glycoprotein and analysis of the fragments revealed that rhamnose is N-glycosidically linked to the amide nitrogen of an asparaginyl residue. PMID- 3342888 TI - Identification of a tetrasialylated monofucosylated tetraantennary N-linked carbohydrate chain in human platelet glycocalicin. AB - Glycocalicin (140 kDa), the main constituent of the glycoprotein Ib alpha-chain (150 kDa) of the human platelet membrane, contains 4 putative N-glycosylation sites. For the structural analysis of the N-glycosidic carbohydrate chains of glycocalicin, the glycoprotein has been subjected to the hydrazinolysis procedure. The acidic carbohydrate chains obtained were fractionated by ion exchange chromatography on DEAE-Sephadex A-25, and subsequently analyzed by sugar analysis, anion-exchange chromatography on Mono Q HR 5/5 and 500 MHz 1H-NMR spectroscopy. A novel tetrasialylated monofucosylated tetraantennary chain was identified in the glycoprotein. It could also be deduced that in all structures the alpha 2----6-linked NeuAc is attached exclusively at the Gal beta 1----2Man alpha 1----3 antenna, whereas the other antennae can be terminated with alpha 2-- -3-linked NeuAc. As minor constituents sialylated N-linked carbohydrate chains with a terminal Fuc alpha 1----2Gal beta 1----sequence were detected. PMID- 3342889 TI - Amino acid sequences of the human kidney cathepsins H and L. AB - The complete amino acid sequences of human kidney cathepsin H (EC 3.4.22.16) and human kidney cathepsin L (EC 3.4.22.15) were determined. Cathepsin H contains 230 residues and has an Mr of 25116. The sequence was obtained by sequencing the light, heavy and mini chain and the peptides produced by cyanogen bromide cleavage of the single-chain form of the enzyme. The glycosylated mini chain is a proteolytic fragment of the propeptide of cathepsin H. Human cathepsin L has 217 amino acid residues and an Mr of 23720. Its amino acid sequence was deduced from N-terminal sequences of the heavy and light chains and from the sequences of cyanogen bromide fragments of the heavy chain. The fragments were aligned by comparison with known sequences of cathepsins H and L from other species. Cathepsins H and L exhibit a high degree of sequence homology to cathepsin B (EC 3.4.22.1) and other cysteine proteinases of the papain superfamily. PMID- 3342890 TI - On the development and use of alloplastic spermatoceles. PMID- 3342891 TI - The government and in vitro fertilization (IVF): views of IVF directors. PMID- 3342892 TI - Treatment of endometriosis by vaginal administration of gestrinone. AB - The effectiveness and acceptability of gestrinone administered by vaginal route was evaluated in a group of 110 patients with endometriosis. Patients were divided into four groups. The first three groups were treated by vaginal route. Group I (n = 17) received two 2.5-mg tablets weekly; group II (n = 31) received three 2.5-mg tablets weekly; group III (n = 35) received two 5.0-mg tablets weekly. Group IV consisted of 27 patients who received 2.5 mg of gestrinone orally twice weekly. Ninety-eight women completed the 6- to 8-month treatment period. Amenorrhea developed in all treatment groups, including group I (34%). The disappearance of both dyspareunia and dysmenorrhea occurred in most patients in all treatment groups soon after the second month of therapy. Patients treated by vaginal route had significantly less seborrhea and acne than those treated by oral route. Weight gain was also significantly less in vaginally treated women than in those treated orally. Pregnancy rate following discontinuation was not significantly different for the various groups. PMID- 3342893 TI - Subtle appearance of pelvic endometriosis. AB - This retrospective study demonstrates an increased documentation of subtle appearances of endometriosis. This documentation was associated with an increased emphasis on excising these lesions for histologic examination. Endometriosis was documented in pink, clear, red, white, and puckered black lesions in 106 (97%) of 109 patients. This included 22 (100%) of 22 patients undergoing laparotomy and 84 (97%) of 87 patients undergoing laparoscopy. Subtle lesions were documented at laparoscopy in 32% of patients in the first 5 months and in 72% of patients in the last 5 months of the study. The increased documentation of these subtle lesions appeared to be related to an increased awareness and anticipation of subtle lesions. The ability to detect such lesions increased with experience and was reinforced by histologic confirmation. PMID- 3342894 TI - Transient hyperprolactinemia during cycle stimulation: influence on the endocrine response and fertilization rate of human oocytes and effects of bromocriptine treatment. AB - The effect of transient hyperprolactinemia and its treatment during cycle stimulation on the endocrine response and fertilization rate of human oocytes was studied. Fifty stimulated cycles were included in the study and divided into three groups: group I consisted of 18 cycles with serum prolactin (PRL) levels less than or equal to 25 ng/ml; group II contained 15 cycles, where patients developed PRL levels greater than 25 ng/ml; group III consisted of 17 cycles, where patients, who already developed hyperprolactinemia in a previous cycle, were treated by 3.75 mg bromocriptine daily. The serum estradiol (E2), progesterone (P) and PRL levels 1, 2, and 3 days before and at oocyte retrieval were evaluated. The E2 decrease at oocyte retrieval was significantly steeper in groups I and III. Follicular luteinization was more effective in groups I and III. The fertilization rate in groups I and III was significantly higher than in group II. High serum PRL levels seem to interfere in follicular and oocyte development. The treatment of transient hyperprolactinemia improved the patients' endocrine response and the fertilization rate of oocytes. PMID- 3342895 TI - Hypoprolactinemia and ovarian function. AB - Thirty-two patients with ovarian hyperstimulation were randomized to receive bromocriptine or placebo from cycle day 5 onward. Bromocriptine decreased serum and follicular fluid prolactin (PRL), accelerated ovarian follicle growth, increased serum and follicular fluid estradiol, lowered luteal phase progesterone, and shortened the luteal phase length of the cycle. The maximal luteal phase estradiol and progesterone concentrations correlated with each other in the placebo group, but not in the bromocriptine group. These findings indicate that hypoprolactinemia interferes with ovarian function. The unchanged concentrations of gonadotropic hormones and pattern of luteinizing hormone pulsation during bromocriptine suggest direct ovarian effects of hypoprolactinemia. Because PRL suppression enhanced follicular responses and inhibited corpus luteum formation and function, the follicular and corpus luteum actions of PRL may be different. PMID- 3342896 TI - Spectrophotometric absorbance of follicular fluid: a predictor of oocyte fertilizing capability. AB - Follicular fluid volume, scoring of the oocyte-cumulus-corona-complex (OCCC), and spectrophotometric absorbance of the follicular fluid were separately compared between a group of fertilized (n = 53) and unfertilized oocytes (n = 35). Scoring of the OCCC and follicular fluid volumes was not found to be statistically different between the two groups. Spectrophotometric analysis of the follicular fluid in the visible spectrum demonstrated two peaks of maximum absorbance at 415 nm and 455 nm. The group of oocytes that fertilized was associated with follicular fluids that had significantly higher absorbances at 415 nm and 455 nm. In conclusion, follicular fluid volume and scoring of the OCCC were poor predictors of fertilizing capability; however, spectrophotometric absorbance, particularly at 455 nm, was positively correlated with oocyte fertilization. PMID- 3342897 TI - Caloric intake, stress, and menstrual function in athletes. AB - The cause of menstrual disturbance in athletes is still debated. Apart from the acute and chronic effects of exertion, other associated behavioral variables are suspected to play a key role. A longitudinal study with frequent blood sampling was undertaken to link information about nutrition and stress with a quantitative assessment of endocrine menstrual function in 18 endurance-trained athletes and 25 age-matched, nonathletic women. Four athletes did not show hormonal signs of follicular development. The 14 athletes with cyclic gonadal function did not differ from controls with regard to estradiol concentrations during the follicular phase and at midcycle. During the luteal phase, however, they showed significantly reduced areas under the estradiol and progesterone curves. Caloric intake, as assessed by nutritional diaries, correlated positively with the area under the progesterone curve during the luteal phase (rs = 0.70, P less than 0.01). Ratings of subjective stress in the area "partner, family, friends" correlated negatively with the luteal progesterone area (rs = 0.80; P less than 0.01). Data support the hypothesis that nutrition and stress may play a critical role in the genesis of menstrual disturbance in athletes. PMID- 3342898 TI - Tubal factor infertility: an association with prior chlamydial infection and asymptomatic salpingitis. AB - In 265 Canadian women, with and without tubal factor infertility (TFI), we compared Chlamydia trachomatis cultures of endocervical swabs, endotubal swabs and biopsies, serology, and past history. A history of pelvic inflammatory disease (PID) was absent in 69.2% of TFI women, despite visual evidence of tubal damage. C. trachomatis was not isolated in any of 52 patients with TFI (TFI group), 114 having tubal ligation (STER group), or 99 patients having hysterectomy (HYST group). However, chlamydial antigen was detected with an immunochemical method in 1 of 16 tubal biopsy specimens from TFI women. The prevalence of chlamydial IgM or IgG antibody in serum was significantly higher (P less than 0.0001) in the TFI group (79.1%) than in the other two groups (relative odds, 6.3; 95% confidence interval: 2.5, 16.8). In seropositive (IgG or IgM) subjects, there was a significant (P = 0.003) and strong (relative odds, 5.1; 95% confidence interval: 1.5, 18.1) association between chlamydial IgA antibody and TFI. In women with TFI, there was no significant association between IgM or IgG seropositivity (P = 0.56). or IgA seropositivity (P = 0.53), and a negative history for PID. These findings are consistent with the hypothesis that C. trachomatis is a major cause of TFI following PID, which may or may not be asymptomatic. PMID- 3342899 TI - Spontaneous luteinizing hormone surge and cleavage of in vitro fertilized embryos. AB - The importance of monitoring luteinizing hormone (LH) secretion during gonadotropin stimulation remains controversial. In the present study, the authors evaluated the occurrence of spontaneous LH surges in 170 cycles stimulated by clomiphene citrate and human menopausal gonadotropin, and correlated the success rate of embryo cleavage to the time interval between the occurrence of the LH surge peak value and the time of human chorionic gonadotropin (hCG) administration. LH was quantitated from urine by an avidin-biotin enzyme immunoassay. The results indicated that a spontaneous LH surge occurred in 18% of the cycles. The number of oocytes recovered was not affected by the occurrence of a spontaneous LH surge. In 12% of all cases, the spontaneous LH surge occurred less than 12 hours before the administration of hCG, and in these cases embryo cleavage was not reduced. In 6% of all cases, the spontaneous LH surge occurred over 12 hours before hCG administration, and in these cases embryo cleavage was reduced significantly. PMID- 3342900 TI - Polyovular follicles associated with human in vitro fertilization. AB - Polyovular follicles were found in 61 (24%) of 251 laparoscopies performed for in vitro fertilization. Of 898 follicles that contained at least one oocyte, 76 (8%) were polyovular. When the oocytes from polyovular follicles were assessed by morphologic criteria, it was found that 46 of the follicles contained oocytes that were discordant in maturity. Thus, oocytes can develop at different rates even though they are exposed to the same follicular fluid. It is possible that the microenvironment provided by the cellular investments of oocytes may correlate more precisely with oocyte maturity. PMID- 3342901 TI - Detection in human sera of antibodies directed against the hamster egg oolemma. AB - Heteroantibodies were demonstrated by indirect immunofluorescence in human sera, which reacted with unfertilized and fertilized hamster eggs. Oolemmal antigens to which these antibodies were directed were distinct from antigen present on the surface of living human spermatozoa. Both species-specific and tissue-specific heteroantibodies were demonstrated by absorption with hamster liver and ovary. An increased degree of heteroantibody binding was noted following penetration of zona-free hamster eggs by human spermatozoa, indicating that an alteration in oolemmal antigen distribution had occurred. No evidence was found, however, that antisperm antibodies in these sera reacted with zona-free hamster eggs following their fertilization. PMID- 3342902 TI - Immunohistologic characterization and quantitation of leukocyte subpopulations in human semen. AB - Various major leukocyte subpopulations (granulocytes, monocytes/macrophages, B lymphocytes, helper and suppressor/cytotoxic T lymphocytes) were detectable in human semen by applying monoclonal antibodies (MAbs) specific for pan-leukocyte and leukocyte subpopulation markers. MAb-labeled cells in smears of washed human semen were visualized by a standard streptavidin-biotin immunoperoxidase method. This approach was validated by testing the MAb panel against sections of human testis and epididymis to rule out cross-reactivity with immature germ cells or other reproductive tract cells, and against peripheral blood leukocytes that had been incubated in human semen to ascertain leukocyte marker stability in seminal plasma. When the immunoperoxidase technique was applied to semen smears from 17 proven fertile men and 51 randomly selected infertility patients, the authors found highly varying total leukocyte numbers, ranging from 8970 to 20,520,000 per ejaculate among fertile men (median, 170,000), and from 43,120 to 104,580,000 among infertility patients (median, 1,035,000). Higher means and medians of granulocytes, monocytes/macrophages, and lymphocyte subsets were seen in the infertility group. These results warrant further investigation on the diagnostic utility of semen leukocyte profiles and the possible role of seminal leukocytes in male infertility. PMID- 3342903 TI - Spermatozoa selection in discontinuous Percoll gradients for use in artificial insemination. AB - In a preliminary study of the ejaculate of 93 men, changes in motility and hypo osmotic swelling before and after sperm separation by discontinuous Percoll gradients were evaluated. Both parameters improved significantly (P less than 0.01) in Percoll-separated spermatozoa. In a second stage, 99 couples underwent intrauterine insemination of separated semen by Percoll gradients. The population had infertility for a mean of 5.6 years. In a 1-year period, a total of 344 intrauterine insemination cycles were completed. Failure was considered when conception did not occur within four treatment cycles. The mean number of cycles per successful couple before pregnancy was 1.52. An overall 21% pregnancy rate was achieved (16% for oligoasthenospermia and 24% for asthenospermia). Sperm separation in Percoll gradients is a useful technique for intrauterine insemination in some cases of male subfertility. PMID- 3342904 TI - Computer-assisted semen analysis: evaluation of method and assessment of the influence of sperm concentration on linear velocity determination. AB - Semen samples from 77 men were used to estimate the accuracy and precision of measurements of sperm density, percent motility, and motion characteristics using a new, fully automated, computer-assisted semen analyzer (CASA). Results are compared with traditional semen analysis methodology. Acceptable precision for count and percent motility was obtained using three to nine random fields of observation when there were more than 10 cells per high-power microscopic field. A highly significant correlation (P less than 0.01) was found between the two methods in the assessment of sperm concentration and percent motility, but CASA overestimated concentration significantly (P less than 0.01) by about 30% when there were less than 60 cells per high power field. This overestimation seemed to be due to the number of nonsperm particles in semen that are confused with spermatozoa by the program. Linear velocity determination was influenced by the number of tracking points as well as by the concentration of cells present in the counting chamber. More representative linear velocity estimations in semen were obtained when sperm concentration was less than 40 x 10(6) cells/ml and 20 tracking points were used in the determination. For semen specimens containing higher cell density, sperm concentration needed to be reduced by diluting the semen with the patient's own sperm-free seminal plasma before measuring motion characteristics. PMID- 3342905 TI - Galactose inhibition of ovulation in mice. AB - Clinical evidence suggests an association between galactosemia and premature ovarian failure. In the present study, adult female mice were fed a diet consisting of 50% galactose for either 2, 4, or 6 weeks. At all times there was a decrease in the normal ovulatory response, as evidenced by a reduction in the number of corpora lutea when compared with controls. Additionally, the exposure of galactose-treated mice to a superovulatory regimen of pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) failed to induce an increased ovulatory response. Morphologic alterations, such as the increase in interstitial tissue and the appearance of lipofuscin, coupled with the failure to respond to exogenous gonadotropins, suggest that the reduced ovulatory response may be occurring at the level of the ovary. This effect, however, is reversible with cessation of galactose treatment. PMID- 3342906 TI - Development of a potentially reversible vas deferens occlusion device and evaluation in primates. AB - A vas deferens occlusion device has been developed and tested in primates. The device consists of two silicone plugs held together by a nylon suture. Implantation of each plug is readily accomplished by making two small puncture holes in the vas deferens and inserting one plug into the lumen toward the epididymis and the other plug toward the seminal vesicles. Implantation is aided by a metal stylus inserted in each plug to give the plug rigidity. The stylus is removed after insertion of the plug into the vas deferens. Two separate primate experiments showed that the device completely prevents sperm transport over a 7 month period. Upon device removal, all of the primates ejaculated spermatozoa again at normal concentrations and motility. These results indicate the potential contraceptive use of the device and encourage its validation in men. PMID- 3342907 TI - Donor oocyte pregnancy with transfer of deep-frozen embryo. AB - An infertile woman suffering from premature menopause conceived on her eighth attempt of ET following the transfer of a single frozen-thawed embryo, the ovum being donated anonymously by a patient undergoing tubal sterilization. PMID- 3342908 TI - Severe thigh myositis following intramuscular progesterone injections in an in vitro fertilization patient. PMID- 3342909 TI - Idiopathic hyperprolactinemia may include a distinct entity with a natural history different from that of prolactin adenomas. PMID- 3342910 TI - Prevalence of ovarian cancer found at the time of infertility microsurgery. AB - We found the prevalence of ovarian cancer in infertile women less than 40 years at the time of planned microsurgery for infertility to be 1 in 95. This may represent a greater prevalence of ovarian cancer than that of all women less than 40 years. Importantly, laparoscopy did not find the ovarian cancer in these women. In conclusion, laparoscopists and microsurgeons need to be aware of the possibility of finding ovarian cancer in these young, infertile women, and this knowledge should be used to counsel and manage the patient appropriately. PMID- 3342911 TI - Proximal tubal occlusion. PMID- 3342912 TI - [Experimental registration of the I.C.U. Experience at the St. Pierre Hospital, Public Center for Social Assistance of Brussels]. PMID- 3342913 TI - [Developmental strategies in nursing care]. PMID- 3342914 TI - [Nurse in hospital hygiene? Observations on a 5-year experience at the Citadel Hospital--Public Center of Social Assistance Liege]. PMID- 3342916 TI - [The nursing care record: study and placement in the Public Center of Social Assistance in Charleroi]. PMID- 3342915 TI - [Current standards for dispensing quality nursing care. Viewpoint of the nursing profession]. PMID- 3342918 TI - The influence of maternal hypnosis on fetal movements in anxious pregnant women. AB - The influence of maternal hypnotherapy on fetal body movements in anxious parturients was studied in 25 patients at 35-37 weeks of gestation. There were two groups of patients. Group A consisted of 16 parturients who performed self hypnosis. Group B consisted of 9 parturients in whom hypnosis was induced by a physician. When compared to a control period of 30 min there was a significant increase in the duration of fetal body movements recorded by ultrasound during 30 min of maternal hypnosis, p less than 0.005 for group A and p less than 0.01 for group B. It is suggested that in anxious parturients fetuses move into a more active state when maternal relaxation is achieved by hypnotherapy. PMID- 3342917 TI - Fetal aortic blood flow and echocardiographic findings in human pregnancy. AB - Relationships between human fetal aortic blood flow parameters and the corresponding echocardiographic findings were investigated in 51 normal, 26 hypertensive and 18 diabetic late pregnancies. In the normal pregnancies the time averaged mean and peak velocities and the waveform indexes of the flow in the fetal aorta were not dependent on the cardiac size nor on the fractional shortening of the myocardium. Total blood flow in the aorta correlated well with heart size and left ventricular output. Hypertensive cases had, as a group, lower aortic velocities and higher waveform indexes than normal and diabetic pregnancies, and the difference from normal was particularly great if the fetus was growth-retarded. Myocardial contractility in these fetuses remained good in spite of these peripheric hemodynamic alterations, but the relative size of the right ventricle was increased. The diabetic cases had smaller blood flow volume in fetal aorta than in the normal cases. In contrast with normal pregnancies the myocardial fractional shortening of these fetuses decreased if the pulsatility of the aortic blood flow increased or the total blood flow in the aorta was high. These findings point to a decreased functional capacity of the fetal heart in a diabetic pregnancy, in particular in the late weeks of gestation. PMID- 3342919 TI - The prevention of sexually transmitted diseases which affect fertility: methodological problems and initial results. AB - Sexually transmitted diseases and their consequences for fertility are currently a major preoccupation in public health. A joint research project is being carried out in France to develop an STD prevention program and then to implement it experimentally to evaluate its efficiency. It includes 2 phases: a feasibility phase, currently concluded, and an active phase, a community randomized trial. The aim of the feasibility phase was to test the research methods and tools and to act as a basis for the design of the prevention program. It measured the incidence of discharge (men and women) at a one-year interval and patient characteristics. Participating physicians were GPs in a French administrative department near Paris. Between the two measurements, information and sensitization actions were carried out in the same department among health professionals and the general public. The results show that the incidence of discharge (chosen here as indicators of STDs) in daily general medical practice is low, of the order of 6 cases per 1000 consultations. The community randomized trial will now be conducted in 6 French administrative departments, randomly divided into 3 treated departments, benefiting from a prevention campaign, and 3 controls, where no actions will be undertaken, and its results will be used in a national STD prevention campaign. PMID- 3342920 TI - Interrelationship between drug oxidation ureogenesis and gluconeogenesis in isolated hepatocytes. AB - 1. The effect of increased ureogenesis--provoked by NH4Cl and ornithine--on gluconeogenesis and aminopyrine oxidation was studied in isolated hepatocytes prepared from 24 hr starved mice; lactate or fructose was used as gluconeogenic precursor. 2. Increased ureogenesis caused about 40% inhibition both on aminopyrine oxidation and gluconeogenesis when lactate was added as gluconeogenic substrate. 3. On the other hand, only 10% inhibition of aminopyrine oxidation and about 15% inhibition of gluconeogenesis were observed when fructose was used as gluconeogenic precursor. 4. Aminopyrine has been reported to inhibit gluconeogenesis from fructose by 30% and from lactate by 85%. The inhibitory effect of the combined addition of aminopyrine, NH4Cl and ornithine on gluconeogenesis was also dependent on the applied gluconeogenic precursor. 5. The provoked ureogenesis by ammonia and ornithine was not inhibited by aminopyrine. N6, O2-dibutyryl cAMP known to cause an increase of gluconeogenesis a decrease of aminopyrine oxidation enhanced the inhibitory action of increased ureogenesis on aminopyrine oxidation and on gluconeogenesis further. 6. The role of NADPH in the regulation of drug oxidation and ureogenesis is underlined. PMID- 3342921 TI - Noncatalytic protein component of elastase from horse leucocytes. A protein with regulatory function. AB - 1. Noncatalytic protein component (NPC), a strongly acidic protein (pH = 4.5) was separated from native horse leucocyte elastase 1. 2. This protein reduces elastinolytic properties of elastases: 1 and 2A probably by decreasing their isoelectric points. 3. A possible regulatory role of this protein may be inferred from a higher affinity of elastase 1 to NPC rather than to elastin. PMID- 3342922 TI - Biochemical evidence for the local synthesis and retention of fibronectin in the tissue of human placenta. AB - 1. Human chorionic tissues were incubated with [14C]leucine and/or [3H]glucosamine, and fibronectin synthesis was examined. 2. Radio-labeled fibronectin was detected in the tissue fraction of the incubation mixture, but not in the medium fraction, indicating that fibronectin is synthesized and retained in the tissue. 3. The glycopeptides derived from 3H-labeled fibronectin showed the lectin-binding characteristics similar to those from unlabeled placenta fibronectin, but different from those of plasma fibronectin. PMID- 3342924 TI - Purification and some properties of low-molecular-weight proteins of Aspidelaps scutatus (shield or shield-nose snake) venom. AB - 1. Fourteen low-molecular-weight proteins from Aspidelaps scutatus venom were purified by gel filtration and ion exchange chromatography. 2. The proteins (toxins) have i.v. LD50 values ranging from 0.12 to 54 micrograms/g mouse. 3. The amino-terminal sequences of the proteins show that 12 of the 14 proteins were pure. 4. The proteins were preliminarily assigned as phospholipases A2, long neurotoxins and cytotoxin homologues. PMID- 3342923 TI - Interaction of neocuproine, 1,10-phenanthroline and 2,2'-dipyridyl with human ceruloplasmin. AB - 1. Neocuproine binding to ceruloplasmin markedly increases the chlorpromazine ceruloplasmin-catalyzed oxidation of NADH. 2. 1,10-Phenanthroline and 2,2' dipyridyl inhibit neocuproine activation in a competitive manner. 3. The order of enzyme chelator complex stability was: phenanthroline greater than dipyridyl greater than neocuproine. PMID- 3342926 TI - Derivative spectrophotometry of dimer and monomer of enolase. AB - 1. SDS causes significant polar exposure of aromatic amino acids of enolase. The alpha-helix content remains unchanged. The enzyme lost all its activity. 2. The presence of 1 M K Br in enzyme solution results in a smaller increase of polarity of aromatic amino acids residues environment. The amount of alpha-helix does not decrease in comparison to native enzyme. Enzyme lost nearly 80% of its initial activity. 3. The extreme pH values and the presence of 6 M Gnd.HCl influence the whole structure of enolase. It is accompanied by a large polar shift of aromatic amino acids and significant decrease of alpha-helix content of the protein. PMID- 3342925 TI - Early effects of oestrogen treatment on lipogenesis de novo and on biosynthesis of triacylglycerol from fatty acids in male chick liver. AB - 1. Early changes (0-44 hr) in liver and plasma lipid levels and in the rate of hepatic lipogenesis were measured in male chicks after a single intramuscular injection of oestradiol-17 beta. 2. Chick liver slices were employed to measure the rate of lipogenesis de novo using 3H2O and the rate of triacylglycerol synthesis from [9, 10-3H] palmitate at various times after injection. 3. The results suggest that oestrogen-induced lipogenesis occurs initially by a rapid and coordinated stimulation of the total hepatic capacity for lipogenesis de novo and for triacyglycerol synthesis from fatty acids. 4. The results are discussed in relation to oestrogen-induced changes in hepatic lipogenic enzymes. PMID- 3342927 TI - Snake venom toxins--I. The primary structure of a long neurotoxin S4C6 from Aspidelaps scutatus (shield or shield-nose snake) venom. AB - 1. Long neurotoxin S4C6 from Aspidelaps scutatus venom was purified by gel filtration and ion exchange chromatography (Joubert, 1987). 2. It contains 68 amino acids including 10 half-cystines. The toxicity of toxin S4C6 was determined and a LD50 of 0.13 +/- 0.04 micrograms/g mouse was found. 3. The complete primary structure of long neurotoxin S4C6 has been elucidated. In the toxin the 10 structurally invariant amino acids of the neurotoxins and cytoxins and the five functionally invariant amino acids of the neurotoxins are conserved. PMID- 3342928 TI - Progressive patterning precedes somite segmentation in the Mexican axolotl (Ambystoma mexicanum). AB - Beginning at mid-neurulation, a wave of somite segmentation passes down the axolotl body axis in a cephalocaudal direction. At 20 degrees C a somite forms every 2.57 hr. Fate-mapping of the presomitic mesoderm indicates that the primordia for the next few somites occupy nearly the same space that they will after segmentation, but that the remaining somites are densely packed in tip of the tail bud. Brief heat shocks at 37 and 38.5 degrees C reveal that within the first of these two zones, there is a graded sensitivity to the shock, with the primordia closest to the last-formed somite showing the greatest resistance. However, primordia within the densely packed tip (the packing zone) also appear resistant, or have sufficient time to repair the damage. We propose that once cells have left the packing zone, they undergo progressive patterning which renders them increasingly insensitive to the disruptive effects of heat shock, and culminates in rosette formation. PMID- 3342929 TI - A neural degeneration mutation that spares primary neurons in the zebrafish. AB - We describe an embryonic lethal mutation in the zebrafish Brachydanio rerio that specifically affects the viability of most cells in the embryonic central nervous system (CNS). The mutation ned-1 (b39rl) was induced with gamma-irradiation and segregates as a single recessive allele closely linked to its centromere. It produces massive cell death in the CNS but a small set of specific neurons, including Rohon-Beard sensory neurons, large hindbrain interneurons, and primary motoneurons, survive embryogenesis and are functional. Synaptic connections between embryonic motoneurons and muscle cells appear physiologically normal, and the normally observed spontaneous flexions are present. Correlated with the presence of sensory neurons and interneurons, mutant embryos display reflexive movements in response to mechanical stimulation. Together, the surviving neurons, called primary neurons, form a class of cells that are prominent in size and arise early during development. Thus, this mutation may define a function that is differentially required by developmentally distinguishable sets of cells in the embryonic CNS. PMID- 3342930 TI - Post-translational control of ribosomal protein L1 accumulation in Xenopus oocytes. AB - A functional ribosomal protein mRNA, encoding the 60 S subunit protein L1, has been synthesized in vitro using bacteriophage SP6 RNA polymerase. This mRNA directs the synthesis of a product indistinguishable from L1 protein purified from Xenopus ovarian ribosomes. Our results show that L1 synthesis in stage VI oocytes increases in response to microinjection of exogenous SP6-L1 mRNA, but excess L1 protein is not stably accumulated. These results indicate that dosage compensation does not occur at the translational level for this ribosomal protein mRNA and that the abundance of this protein in fully grown oocytes is subject to post-translational regulation. PMID- 3342931 TI - 20-Hydroxyecdysone accelerates the flow of cells into the G1 phase and the S phase in a male accessory gland of the mealworm pupa (Tenebrio molitor). AB - The cells of the bean-shaped accessory glands of mealworms proliferate through the first 7 days of the 9-day pupal stage. Immediately after larval-pupal ecdysis, 25-27% of the cells were in the G1 phase, 60-65% were in the G2 phase, and the balance were in S phase. Over the first 4 days of normal development, the S fraction gradually increased, to reach its highest level in the mid-pupa at the time of the major ecdysteroid peak (Delbecque et al., 1978). Thereafter, the S fraction declined until over 95% of the cells had accumulated in G2 on Day 8. When 0-day pupal glands were explanted into Landureau's S-20 medium for 6 days, the G1 fraction remained fairly constant (25-30%) while S and the G2 fractions fluctuated. On the first day in vitro, the G2 fraction declined and the S fraction rose. On the second day in basal media, the S fraction fell and G2 rose correspondingly until 70% of the cells reached G2 when cycling stopped on the third day. With addition of 20-hydroxyecdysone to 0-day cultures, the S fraction increased quite sharply. It remained large for all 6 days of the experiment in the continuing presence of hormone. A 1-day pulse of hormone produced a transient increase in S. We blocked cell cycling with hydroxyurea in a stathmokinetic experiment and showed that 20-hydroxyecdysone accelerated the flow of cells from the G2 phase to the G1 phase by 2.5-fold. An increase in the G1 fraction was detected within 10 hr of hormone administration and the effect was dose-dependent with an ED50 of 5 X 10(-7) M for 20-hydroxyecdysone. We conclude that 20 hydroxyecdysone acts at a control point in the G2 phase. Incubation of the glands with 20-hydroxyecdysone for only 30-60 min followed by washout stimulated the flow from G2 to G1 and the effect persisted after transfer of the tissues to hormone-free media. Dose-dependent stimulation also occurred with ponasterone A (ED50 3 X 10(-9] but not with cholesterol. PMID- 3342933 TI - Further experimental evidence for the involvement of ecdysone in the control of meiotic reinitiation in oocytes of Locusta migratoria (Insecta, Orthoptera). AB - Ecdysone has recently been shown to be able to trigger meiotic reinitiation in vitro in submature oocytes of Locusta. In the present study we have experimentally depressed (by 60-70%) ecdysone biosynthesis in the ovaries of adult females by rearing them on a diet with a modified sterol profile. Mature oocytes from such females fail to undergo normal reinitiation, but when incubated in vitro, can be induced to break their meiotic arrest by the addition of exogenous ecdysone. These results lend further support to the hypothesis that in Locusta, ovarian ecdysone is involved in the control of meiotic reinitiation. PMID- 3342932 TI - Heparin inhibits skeletal muscle growth in vitro. AB - Heparin or heparan sulfate proteoglycan (HeSPG), but not chondroitin sulfate or hyaluronic acid, exerts a pronounced inhibitory effect on muscle growth in vitro, as determined by total protein, myosin accumulation or synthesis, and [3H]thymidine incorporation studies. Primary muscle fibroblast culture growth is also inhibited by heparin but to a substantially lesser degree compared to muscle (30% and over 90% inhibition of growth, respectively). Heparin-induced inhibition of skeletal muscle growth is a consequence of its interaction with a growth factor(s) present in the media used to support myogenesis; heparin-Sepharose column absorbed horse serum can support muscle growth only in the presence of added heparin-binding growth factors like fibroblast growth factor (FGF) or chicken muscle growth factor (CMGF). Furthermore, heparin prevents the binding of iodinated FGF to the myoblast surface. We also show that the extent of muscle growth is a function of the relative amounts of heparin and FGF in culture. Finally, we provide evidence indicating that FGF can combine with endogenously occurring heparin-like components: immobilized FGF binds sodium-[35S]sulfate labeled components secreted in muscle culture conditioned medium, an interaction inhibited by anti-HeSPG antibodies or heparin, but not by other sulfated glycosaminoglycans. Since heparin binding growth factors not only stimulate myoblast proliferation but also actively inhibit the onset of muscle differentiation (G. Spitzz, D. Roman, and A. Strauss (1986). J. Biol. Chem. 261, 9483-9488), their interaction with naturally occurring heparin-like components may be an important physiological mechanism for modulating muscle growth and differentiation in development and regeneration. PMID- 3342934 TI - Growth cone guidance by substrate-bound laminin pathways is correlated with neuron-to-pathway adhesivity. AB - Substrate-bound laminin pathways prepared by the method of Hammarback et al. [J.A. Hammarback, S.L. Palm, L.T. Furcht, and P.C. Letourneau (1985). J. Neurosci. Res. 13, 213-220] guided peripheral nervous system neurites (dissociated dorsal root ganglia and sympathetic ganglia) and central nervous system neurites (dissociated spinal cord and brain). Guidance of individual growth cones by 7- to 10-micron-wide laminin pathways was observed using time lapse video microscopy. Fibronectin pathways, produced by the method used for laminin pathways, did not guide neurites. The guidance effect of laminin pathways was quantified and found to correlate with the concentration of laminin initially applied to the substratum. The concentration of laminin initially applied to the substratum also correlated with increased adhesivity of dorsal root ganglia (DRG) neurons to laminin constituting the pathways relative to uv-irradiated laminin that borders the pathways. The guidance effect of laminin pathways was blocked by anti-laminin antibodies or by laminin but not by anti-fibronectin antibodies. This study demonstrates that guidance of DRG neurites by laminin occurs at the growth cone in a manner consistent with the hypothesis of guidance by differential neuron-to-substratum adhesivity. PMID- 3342935 TI - Developmental changes of nerve growth factor levels in sympathetic ganglia and their target organs. AB - The predominant source of nerve growth factor (NGF) used by mature sympathetic neurons originates in their target organs (Heumann, R., Korsching, S., Scott, J., and Thoenen, H. (1984), EMBO J. 3, 3183-3189; Korsching, S., and Thoenen, H. (1985), J. Neurosci. 5, 1058-1061). We have determined the NGF content of two sympathetically innervated mouse organs, submandibular gland and heart ventricle, and of sympathetic ganglia from mouse and rat between embryonic Day 12 (E12) and adulthood. NGF levels were measured by a two-site enzyme immunassay (Korsching, S., and Thoenen, H. (1983), Proc. Natl. Acad. Sci. USA 80, 3513-3516). In heart ventricle and submandibular gland, NGF first became detectable around the time of initial innervation by sympathetic neurons (E12 and E13, respectively) and increased respectively 14- and 7-fold in the following 2 days, to reach adult levels already at E14 for heart ventricle (1.4 +/- 0.2 ng NGF/g wet wt). NGF in the superior cervical ganglion (SCG) was first detected at the same time as in its target organ, the submandibular gland. NGF content in the SCG then increased 6-fold during the next 2 days and continued to increase until the end of the third postnatal week, when adult levels were reached. Although the levels of NGF in the adult mouse submandibular gland are sexually dimorphic and six orders of magnitude higher than those in other sympathetic target organs, no sex difference in the NGF content was found in either developing submandibular gland or SCG until the end of the third postnatal week. Moreover, the steep NGF increase observed in the male submandibular gland after postnatal Day 18 (250-fold within the following 3 days and up to the 55,000-fold in the next 7 days) was not reflected in a corresponding increase in the NGF content of the male SCG. These data indicate that, in accordance with earlier findings (see Levi-Montalcini, R., and Angeletti, P. U. (1968), Physiol. Rev. 48, 534-569), SCG neurons do not have access to the large amounts of NGF synthesized during and after adolescence in the mouse submandibular gland. Our results support the concept that initial fiber outgrowth of sympathetic neurons is neither dependent on NGF nor mediated by it. The time course of NGF levels in the SCG is consistent with the concept that sympathetic neurons are provided with NGF by means of retrograde axonal transport from the innervated organs already early in development. PMID- 3342937 TI - Extravascular fluid dynamics of the embryonic chick wing bud. AB - While a number of models of positional information in the chick wing bud have involved the diffusion of morphogens to establish chemical gradients of morphogenetic activity, only recently have there been attempts to characterize the milieu in which such diffusion must take place. We report an analysis of the fluid dynamics of the extravascular (interstitial) spaces of stage 22-25 chick wing buds, into which aqueous aniline blue dye was microinjected as a visible, unreactive tracer. Six sites along the antero-posterior (A-P) and proximo-distal (P-D) axes were chosen for study. Injections of dye into the posterior half of the wing bud exhibited marked directionality of extravascular transport (mean of all posterior sites = 68%), while anterior injections showed little or no directionality (mean of all anterior sites = 13%). All instances of directed dye movement were disto-proximal, the same direction as the blood flow through the marginal veins. In embryos gassed in situ with CO2, which reversibly stopped the heartbeat and vascular flow, directionality was abolished, yet diffusion rates were unaffected. Posterior disto-proximal extravascular dye movement was correlated with the greater diameter, flow velocity, and volume flow rate of the posterior marginal vein, compared to the anterior marginal vein. Radial diffusion rates were measured, and posterior disto-proximal rates were corrected for measured disto-proximal directionality by the use of a simple diffusion translation model. Three-way analysis of variance showed that directionality uncorrected disto-proximal rates in posterior sites were not significantly different from anterior radial rates, but that directionality-corrected posterior rates did differ significantly (P less than 0.0001). A significant stage effect (P less than 0.005) and a significant interaction between the A-P axis and stage (P less than 0.05) were also found. We hypothesize that the spatial arrangement and flow patterns of the vasculature physically determine the fluid dynamics of the interstitium. Based on these observations, we also suggest that disto proximal extravascular fluid movement in the posterior wing bud presents a barrier to the free diffusion of aqueous molecules, including morphogens originating in the "zone of polarizing activity." PMID- 3342936 TI - Increase in intracellular calcium induced by the polycation-coated latex bead, a stimulus that causes postsynaptic-type differentiation in cultured Xenopus muscle cells. AB - The polycation-coated latex bead is a potent stimulus for the induction of postsynaptic-type differentiation in cultured Xenopus myotomal muscle cells. Specializations characteristic of the neuromuscular junction, such as clusters of acetylcholine receptors and other postsynaptic-specific proteins, develop at the bead-muscle contact. Previous studies have shown that a deprivation of extracellular calcium inhibits the effect of the beads in causing the development of these specializations. This suggests that an increase in intracellular Ca2+ is a necessary condition for the development of this specialization. In this study, we tested whether an increase in intracellular calcium is observable upon the bead-muscle contact. The measurement was carried out on cells loaded with the fluorescent calcium indicator fura-2 AM by digitized video microscopy. When polycation-coated beads were added to cells, an increase in intracellular calcium concentration in the range of 5 to 57% of the resting level was observed within 10 sec after bead-muscle contact. Afterward, the calcium level gradually returned to the resting level with a time course of about 3 min. Uncoated beads, which do not induce the formation of acetylcholine receptor clustering, failed to elicit this calcium transient. Removal of extracellular calcium as well as blocking calcium channels with 50 microM verapamil also suppressed this transient induced by the polycation-coated beads. Both treatments are known to suppress the formation of receptor clusters by these beads. These results suggest that the polycation-coated beads cause an influx of calcium by increasing the membrane conductance to this ion. This process may underlie the signaling of the postsynaptic differentiation. PMID- 3342939 TI - Immunocytochemical localization of protein kinase C in developing brain tissue and in primary neuronal cultures. AB - Antisera to protein kinase C (PKC) have been used to examine the presence and distribution of the enzyme in developing cerebellar cortex of postnatal rat and in cultures of rat sympathetic ganglia. In the cerebellar cortex of 2-,4-, and 6 day old rats, immunostaining was observed in areas of early-forming presynaptic terminals and growth cones. No staining was evident in the cortical proliferative zone. Beginning at 10 days postnatal, nuclear staining, not apparent at earlier stages, was prominent in Purkinje cells. In neuronal cultures of dissociated rat sympathetic ganglia, PKC was immunolocalized in cell bodies and bundles of neuronal processes. Immunoreactivity was particularly striking in growth cones of extending neurites and in axonal varicosities. These results suggest a role for PKC in neuronal growth following cell proliferation and in synaptic function. The appearance of nuclear staining in later developmental stages suggests that the enzyme may be involved in the promotion and maintenance of the differentiated state of neurons. PMID- 3342938 TI - Infertility due to growth arrest of ovarian follicles in Sl/Slt mice. AB - Sl, Sld, and Slt are mutant alleles at the steel locus. All Sl/Sld and most Sl/Slt female mice are infertile, but the cause of the infertility is different. Germ cells are absent in Sl/Sld ovaries but present in Sl/Slt ovaries. The infertility of Sl/Slt female mice was attributed to the growth arrest of ovarian follicles, and the mechanism was analyzed by producing aggregation chimeras between Sl/Slt and +/+ embryos. Sl/Slt oocytes were ovulated and fertilized in Sl/Slt----+/+ chimeras. We investigated the origin of granulosa cells in the growing follicles and that of granulosa-derived luteal cells in the chimeras by using the electrophoretic pattern of phosphoglycerate kinase-1 and the histochemical activity of beta-glucuronidase as markers. Granulosa cells of Sl/Slt genotype developed and constituted pregnant corpora lutea in Sl/Slt----+/+ chimeras. Therefore, the growth arrest of Sl/Slt ovarian follicles may not be due to an intrinsic defect in granulosa cells but may instead be due to an intrinsic defect in ovarian stromal cells. This suggests that normal stromal cells are essential for the development of ovarian follicles. PMID- 3342940 TI - Effects of an adaptive filter hearing aid on speech recognition in noise by hearing-impaired subjects. AB - In a digitally controlled adaptive filter, ongoing detection and spectral analysis of quasi steady state noise are performed, and analog filter parameters are adjusted to provide greatest attenuation in frequency regions where noise energy is greatest. Attenuation introduced by the filter affects both speech and noise signals in the attenuation region. Effects of a master hearing aid incorporating an adaptive filter chip were assessed by measuring aided speech recognition threshold in noise with and without the filter. Performance of four hearing-impaired subjects showed that filter effects were related both to the frequency spectrum of the noise and to the distribution of speech information by frequency. No improvement in speech recognition threshold was seen for broadband speech materials in broadband noise. Better performance was observed for low frequency noise in combination with speech materials for which the important information was confined to high frequencies. PMID- 3342941 TI - An experimental comparison of four hearing aid prescription methods. AB - Four hearing aid prescription methods were compared. A digital master hearing aid was used to produce the prescribed frequency gain characteristics. Measures of speech recognition and paired comparison judgments of relative speech intelligibility and speech quality were obtained at three output levels for each of the experimental frequency gain characteristics. No single prescriptive method emerged as being clearly superior. Relative performance of the four prescriptive methods varied as a function of output level. Similar results were observed for both speech recognition testing and paired comparison testing. PMID- 3342942 TI - A new protocol for assessing viseme perception in sentence context: the lipreading discrimination test. AB - Forty-six hearing-impaired young adults were tested with a newly developed instrument that requires a discrimination response to assess viseme perception as a component of lipreading performance. Stimuli were videotaped sentences that differed on half of the trials from a captioned target sentence by one viseme embedded in the middle of the sentence. Discrimination within six visual categories was tested: gross syllable pattern, consonant articulation--lips, consonant articulation--tongue, vowel articulation--extreme lip shapes, vowel articulation--graded lip shapes, and vowel articulation--jaw movement. Test data were analyzed using an item response theory model. The results indicated that the test data conformed to the expectations of the Rasch model for person measurement. Relationships among subjects' test scores and communication characteristics also were examined. The data provide evidence that the test protocol, at this early stage of development, is useful for assessing at least one perceptual component of lipreading performance. PMID- 3342943 TI - Prediction of dynamic range from stapedius reflex in cochlear implant patients. AB - Amplitude growth functions of the electrically elicited stapedius reflex were compared with behavioral estimates of dynamic range in seven patients using multielectrode cochlear implants. The range between threshold and saturation level of the amplitude growth function usually either encompassed or fell between the preferred and uncomfortable listening levels. Implications of these findings for the initial mapping of electrodes in young children are discussed. PMID- 3342945 TI - Digital filtering and spectral analysis of the low intensity ABR. AB - Spectral analysis along with zero and standard-phase shift digital filtering were performed on evoked potentials recorded from 12 normal hearing subjects. The results indicated a progressive shifting of the mean spectral content of the ABR toward the low frequencies as the stimulus intensity was lowered. Despite this, the effects of zero-phase shift high-pass digital filtering at 100 Hz (36 dB/oct) did not significantly differ between waveforms elicited by a 75 dB nHL, 55 dB nHL, and 35 dB nHL stimulus. The major response frequency of the ABR is related to the distance between the peak (IV/V) and the following major trough (approximates one-half the response period). In waveforms where the major trough occurred before 10 msec, the use of 100 Hz, 36 dB/oct, zero-phase shift high-pass filters produced only a small reduction in response amplitude, even at low stimulus intensity levels. Waveforms which had a major trough (Na1) between 10 to 15 msec were reduced in amplitude by 100 Hz, 36 dB/oct, zero-phase shift high pass filters (the longer period of the response energy in these waveforms corresponds to a lower energy frequency). However, this trough has a latency that prevents it from being recorded on a 10 msec time base or defined as an ABR. Based on these results, the use of zero-phase shift high-pass filters with a high pass cutoff frequency that is equal to or less than the resolution of the time base (1/time base) appears to be a desirable method of reducing muscle artifact and other electrical contamination of the ABR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3342944 TI - Asymmetric hearing loss in truck drivers. PMID- 3342947 TI - Absenteeism in nursing: a case study. PMID- 3342946 TI - Observations on the acoustic reflex threshold in institutionalized retarded adults taking mellaril and/or thorazine. AB - The present study was designed to investigate whether mellaril and thorazine, when used alone and in combination with other medications by mentally retarded clients, either abolish acoustic reflexes or compromise estimates of hearing sensitivity based on acoustic reflex measures. Acoustic reflex thresholds were determined in 35 normal-hearing institutionalized mentally retarded subjects who were regular users of the medications under investigation. Five sensitivity prediction methods based on acoustic reflex thresholds were applied to the data. The results of the study showed that acoustic reflexes were present in most subjects. However, the accuracy of all the acoustic reflex-based sensitivity prediction methods was quite poor with greatly exaggerated predictions of hearing loss. The methods based solely on noise reflex thresholds provided better accuracy than those based on noise-tone differences. In general, the accuracy of the prediction methods decreased as the number of medications used by the subjects increased. It is argued that the results provide evidence for reticular activating system mediation of acoustic reflex activity. PMID- 3342948 TI - The information gap: blood bank to bedside. PMID- 3342949 TI - An interdisciplinary approach to domestic abuse. PMID- 3342951 TI - Computerizing medical records: the future is here. Part 2. PMID- 3342950 TI - Do pediatric units' school programs make the grade? PMID- 3342952 TI - An open letter to infection control personnel. PMID- 3342953 TI - Resuscitating newborns. PMID- 3342954 TI - Breathing new life into neonatal resuscitation guidelines. AB - The problems surrounding neonatal resuscitation are complex. The rarity of the event, the complexity of the procedure and the variety of professionals involved are some of the factors that contribute to the difficulties. It is extremely encouraging that all of the professionals involved are committed to working together to improve the quality of care for babies in Canadian hospitals. PMID- 3342955 TI - Family diseases and family history. PMID- 3342956 TI - Computers and family practice: tools of the trade. PMID- 3342957 TI - Blood pressure measurement in family physician offices. AB - In January of 1986, board certified family physicians in 407 medical offices within New York state were surveyed to ascertain the range of blood pressure (BP) equipment available in their offices. Information regarding the calibration of anaeroid BP cuffs was also obtained. Most physicians in the sample who saw infants and children in their office did not carry infant-size BP cuffs. Several respondents did not carry an adequate range of BP cuff sizes suitable for small or large adult arms. Additionally, the majority of family physicians in the sample did not calibrate their BP cuffs in accordance with manufacturer's recommendations. In general, the evidence accumulated leads to questions about the overall accuracy of BP measurement in family physician offices. PMID- 3342958 TI - Geriatric fellowships in family medicine: status and directions. AB - The American Board of Medical Specialties recently approved the concept of certificates of added qualifications in geriatrics within both internal medicine and family practice. Certification requirements have been worked out for each training model, and questions have quite naturally arisen addressing whether the developing family practice model is substantially different from the longer established internal medicine model. A survey was made of 12 family practice based geriatric fellowship programs. Program directors were asked how they felt family practice geriatrics differed from internal medicine geriatrics in approaches to patient care and training and in areas of research interests. Information was also gathered about program size, length of training, and operational status. Eight fellowship programs were found to be active at the time of the survey, but only two for more than six months. Of the eight functioning programs, four were currently without fellows--a forewarning, perhaps, of potential recruitment problems for additional programs under development. Survey responses indicated a universal feeling among directors of family practice geriatric programs that their model does serve a unique function. Within the "distinguishing characteristics" most frequently noted, an emphasis on psychosocial and family issues can be identified. This emphasis can also be seen in the suggestions for distinctive research, with an indication of special interest in the delivery of health care. PMID- 3342959 TI - Profiles of family practice faculty development fellowship graduates 1978-1985. AB - This paper describes the academic roles of the 1978 through 1985 graduates of family medicine faculty development fellowship programs sponsored by the Robert Wood Johnson Foundation (RWJ) and the Division of Medicine of the U.S. Department of Health and Human Services (HHS). A total of 329 alumni from 12 of the 59 HHS programs and all five of the RWJ programs were surveyed. Based on a 74% response rate, profiles are drawn of graduates. These profiles are compared to a review of the literature in higher education on fellowships, faculty attrition, faculty activities, tenure, and promotion. Conclusions reached from these comparisons include: (1) The retention rate of fellows in full-time faculty positions equaled or exceeded those of other fellowships found in the literature. (2) The attrition rate of alumni from faculty positions has been less than that noted of faculty in other areas of higher education. (3) On average, fellowship graduates have spent less time in research activities than recommended for productivity. (4) The emphasis on research training, particularly in RWJ fellowships, was appropriate, given increasing expectations for research productivity in tenure and promotion decisions. (5) The national trend toward development of alternatives to traditional tenure tracks matches the patterns found in family medicine fellowship alumni--31% of these alumni were serving on such tracks. PMID- 3342960 TI - The effects of learners on waiting times and patient satisfaction in an ambulatory teaching practice. AB - Data regarding waiting times and times with nurses and physicians were recorded for 656 patients visiting a large family practice unit. Patients also provided estimates of their own waiting times and ratings of the acceptability of these waits. The data were analyzed to assess whether any differences exist in terms of waiting times, times with providers, and waiting time satisfaction for patients seen by clinical clerks (medical students), resident physicians, and attending physicians. Consultation times were longer for patients seen by learners, but waiting times were shorter for these patients. Importantly, there were no significant differences in terms of patient satisfaction with consultation time or waiting time satisfaction. Thus, while learners made a noticeable impact on consultation time, the overall effect on the patient booking system was marginal, and there was no negative impact on patient wait time satisfaction. To control for unevenness of type of providers assigned to the different services, only intermediate assessments are included in this study. The conclusions should not be generalized for other types of services. PMID- 3342962 TI - Systems analysis and guidelines for behavioral scientists in family medicine. AB - A recurrent theme among behavioral scientists is the difficulty of being a nonphysician in a medical setting. Differences in training and in work roles can create misunderstanding between physicians and behavioral scientists; and being a minority in terms of profession can be isolating and demoralizing. To date, analyses have focused on the individual differences between the two groups and not on the context--the larger system--in which the two work. This article examines these systemic problems, particularly problems specific to family medicine. Coping methods which can be used by behavioral scientists are proposed to help them reduce the work stress they experience. PMID- 3342961 TI - Influenza vaccination: a comparison of two outreach strategies. AB - Despite longstanding recommendations for annual influenza vaccination of all people age 65 and older, only 20% or less are regularly immunized. This paper compares two methods of immunization outreach to the elderly population. In 1985 and 1986 vaccine was offered to patients who attended one family practice for any reason during the months of October and November. In 1985 if patients had not received vaccine by October 31 an informational letter recommending immunization was also mailed. In 1986 nonimmunized patients were telephoned by the family practice nurse and informed of the rationale, availability, and advisability of receiving the vaccine. The immunization rate improved in patients attending the practice over the two study years. Additional outreach efforts showed a high degree of failure or refusal to receive immunization. PMID- 3342963 TI - Establishing a rural family practice research network. AB - One approach to addressing the deficit in the primary care knowledge base is to answer clinical questions using a consortium of collaborating practices. Previous reports have described networks that collect descriptive data from many practices, but there are difficulties in establishing and managing large networks. Accordingly, smaller networks may be more valuable in some settings and for some clinical questions. At the University of Missouri, we have developed a research network composed of four rural family practices and a group of study coordinators. Research topics have been chosen, study methods devised, funding obtained, and valuable data collected. Although logistical problems with any diverse network are formidable, a structured approach with careful communication can overcome these difficulties. The lessons from this experience combined with those of larger primary care networks should assist others in implementing research consortiums. Collaborative research by family physicians is practical, feasible, personally and professionally rewarding, and likely to contribute important primary care knowledge. PMID- 3342964 TI - Primary care for the mentally retarded: one residency's experience. PMID- 3342965 TI - The "one-and-two" family practice residency revisited. AB - First brought to the attention of the medical education community in 1977, the "one-and-two" program was designed to improve the relevance of residency training by using both a university teaching hospital and a smaller community hospital as training centers. This paper reviews the progress of implementing this format over the past ten years, and cites some of the advantages and disadvantages encountered from doing so. PMID- 3342966 TI - Behavioral science in family medicine (again). PMID- 3342967 TI - Irreversible injury in anoxic hepatocytes precipitated by an abrupt increase in plasma membrane permeability. AB - Using low-light digitized video microscopy, the onset, progression, and reversibility of anoxic injury were assessed in single hepatocytes isolated from fasted rats. Cell-surface bleb formation occurred in three stages over 1-3 h after anoxia. Stage I was characterized by formation of numerous small blebs. In stage II, small blebs enlarged by coalescence and fusion to form a few large terminal blebs. Near the end of stage II, cells began to swell rapidly, ending with the apparent breakdown of one of the terminal blebs. Breakdown of the bleb membrane initiated stage III of injury and was coincident with a rapid increase of nonspecific permeability to organic cationic and anionic molecules. On reoxygenation, stages I and II were fully reversible, and plasma membrane blebs were resorbed completely within 6 min of reoxygenation without loss of viability. Stage III, however, was not reversible, and no morphological changes occurred on reoxygenation. The results indicate that onset of cell death owing to anoxia is a rapid event initiated by a sudden increase of nonspecific plasma membrane permeability caused by rupture of a terminal bleb. Anoxic injury is reversible until this event occurs. PMID- 3342968 TI - Bile acid synthesis: down-regulation by monohydroxy bile acids. AB - The regulation of bile acid synthesis was studied in rabbits after interruption of the enterohepatic circulation by choledochoureteral anastomosis. Total daily bile acid output was 772 +/- 130 (SD) mumol/24 h, of which greater than 95% was glycocholic acid. Administration of deoxycholic or cholic acid or their conjugates (300-800 mumol) or gall-bladder bile failed to down-regulate endogenous bile acid synthesis. In contrast, chenodeoxycholic acid administration did down-regulate bile acid synthesis, but this effect was related to the formation and excretion of lithocholic acid. This observation was confirmed by the finding that i.v. infusion of 10-20 mumol of either lithocholic acid or 3 beta-hydroxy-5-cholenoic acid significantly reduced cholic acid synthesis. Thus monohydroxy bile acids, derived from either hepatic or intestinal sources, participate in the down-regulation of bile acid synthesis. PMID- 3342969 TI - Geriatric knee disorders, Part II: Differential diagnosis and treatment. AB - Part II of this two-part article reviews differential diagnosis of common geriatric knee disorders. Differentiating extra-articular from intra-articular causes of knee pain is stressed, since treatments and prognoses can be quite different. Referred pain from the ipsilateral hip and spine should also be kept in mind. The diagnostic approach to knee pain can be categorized anatomically and according to etiology: Is the pain coming from the bone (patella, femur, tibia, fibula), or the soft tissue (ligament, tendon, capsule, synovium, meniscus, muscle)? Is it degenerative, inflammatory, metabolic, traumatic, infectious, or neoplastic? These issues are included in the discussion. PMID- 3342970 TI - Cerebrospinal fluid absorption in the rabbit. Optic pathways. AB - Fifteen rabbits were intrathecally perfused with horseradish peroxidase at normal cerebrospinal fluid pressures. Horseradish peroxidase was found in the subarachnoid space around the optic nerve; it permeated the pia and penetrated within the nerve, occupying extracellular spaces between myelinated axons and glial cells up to the area of the lamina cribrosa. Horseradish peroxidase also crossed the perineural sclera and the border tissue of Elschnig to spread into the choroid where it was mostly seen within choriocapillaris, venules, and veins crossing through interendothelial spaces. "Bulk" cerebrospinal fluid absorption in the eye appears to occur through venous drainage in the choroid and SAS. PMID- 3342971 TI - Histopathological study of Emory mouse cataract. AB - Lenses of Emory mice, ranging in age from 7 days to 15 months, were studied by light and electron microscopy. The earliest change was acellularity in the lens epithelium, which was found at postnatal day 14. This acellularity was relatively mild but constantly occurred throughout the experimental course. The early cortical fiber change was swelling in the anterior region of the lens at 1 month of age. At 2 months of age some cell extensions towards the capsule appeared at the basal surface of the posterior cortical fibers near the equatorial region, and their height and number had greatly increased by 4 months of age. Following this change, there was an enlargement of nuclei in the bow area, swelling of cortical fibers, and separation of the posterior suture line. These changes became severe by 6 months of age. When the separation of the posterior suture and disturbance of the posterior cortical fibers became markedly severe, the cataract reached a mature stage, showing the complete opacity of the cortex. This animal model appears to indicate that the viability and/or behavior of the epithelial cells is important for maintaining the transparency of the lens throughout the lifespan. PMID- 3342972 TI - Congenital retinal folds in Sheffield-Wistar rats. AB - Retinal folds are described in male rats of a Wistar-derived strain, which occasionally shows microphthalmia and cataract. The less severe lesions mainly affect the outer retinal layers and contain microretinal detachment, cell rosettes, phagocytic cells and lipid debris. More severe folds involve all the retinal layers, exhibit subretinal haemorrhage, and photoreceptor outer segment debris throughout the lesion and on the vitreal surface. The lesions are discussed in relation to previous observations of retinal folds. PMID- 3342973 TI - Multiple evanescent white dot syndrome. AB - Multiple small infiltrates deep in the retina were found in three previously healthy patients aged 21-28 years in association with a mild non-specific acute infection. In two patients the lesions were uniocular, in one patient both eyes were affected. Both posterior pole and midperiphery were involved. In two cases the optic disk was slightly swollen. Due to macular lesions the visual acuity on admission varied from 0.1 (6/60) to 0.6 (6/10). On fluorescein angiograms the lesions were initially hypofluorescent and later slightly hyperfluorescent. No causative agents were discovered. All lesions resolved in 4-8 weeks without treatment, leaving faint pigment dispersion or, more commonly, no visible scars, and the visual acuity recovered to 1.0 (6/6). PMID- 3342974 TI - Human cornea: superior and central oxygen demands. AB - Corneal oxygen demands, expressed as ratios of uptake rate relative to baseline rates derived from unstressed corneas, were determined with a micropolarographic system for central (closed eye) and superior (open eye) locations of one cornea of each of seven human subjects. The closed-eye central corneal measurements were repeated during two additional experimental sessions. Intrasubject variability of the three mean closed-eye central corneal rate ratios ranged as high as 23%, possibly representing effects of homeostatic mechanisms on the palpebral conjunctival capillaries of some subjects. For the open-eye superior cornea, which was covered by the upper eyelid of every subject prior to measurement, oxygen demand was found to have a greater intersubject range, but was diminished in magnitude relative to the demand associated with the closed-eye central cornea. Superior corneal oxygen demand was not found to be predictable from closed-eye central corneal oxygen demand or extent of eyelid overlap onto the cornea and thus indicated localized open-eye superior corneal environments that were significantly different from those of the corresponding closed-eye central corneas. Such localized environments may be critically important when gauging the susceptibility of particular eyes to superior corneal pathology during contact lens wear. PMID- 3342975 TI - Human cornea: individual responses to hypoxic environments. AB - Using a micropolarographic system, the responses of seven human corneas to oxygen atmospheres ranging from 20.9% to 0% were measured. Under normal atmospheric conditions, ratios of oxygen demand were observed between corneas as great as 1.23:1. Following 0% oxygen conditions, however, these ratios rose to a maximum of 1.93:1, i.e., representing demand differences between particular corneas of nearly 2:1. Such differences may prove increasingly important in the gauging of patient suitability and safety in relation to hypoxic stress, e.g., the extended wear of contact lenses. PMID- 3342977 TI - Quantification of choroidal blood-flow parameters using indocyanine green video fluorescence angiography and statistical picture analysis. AB - A method for indocyanine green video-fluorescence angiography of the human choroid is described using a 30 degrees fundus camera (C. Zeiss) with external light supply, a low-light-level TV camera, and a video recorder. Bloodflow parameters for the choroid were obtained from the video recording using a picture analysis system (IBAS, Kontron). These included: the mean time for arterial, capillary and venous filling and a parameter corresponding to the amount of perfused capillaries in the choroid. Angiograms were performed on normal, healthy subjects at normal and increased intraocular pressures and on patients with dry senile macular degeneration. Examples of the results are shown and discussed. PMID- 3342976 TI - Neodymium: YAG laser iridotomies--short-term comparison with capsulotomies and long-term follow-up. AB - This study addresses three aspects of anterior segment Nd:YAG laser treatment- acute endothelial damage, as assessed by endothelial specular photomicrography (ESP), acute and long-term intraocular pressure (IOP) changes, and long-term iridotomy patency. The acute ESP and IOP changes in 26 eyes (21 patients) after Nd:YAG laser iridotomies were compared to 39 eyes (37 patients) after Nd:YAG laser capsulotomy. Similar endothelial damage occurred in both groups, although less damage was noted in the group of 9 eyes in which capsulotomies were undertaken in the presence of an intraocular lens. In a parallel study 53 eyes (44 patients) were followed for a mean of 83 weeks (19 months) from the time of Nd:YAG iridotomy. There were no late closures and no late rises in IOP. The level of acute IOP rise after treatment did not predict long-term IOP. We conclude that Nd:YAG iridotomy is an effective procedure in the long-term, and that both iridotomy and capsulotomy are accompanied by noteworthy acute endothelial changes and intraocular pressure rises. PMID- 3342978 TI - Massive intraocular hemorrhage associated with anticoagulation and age-related macular degeneration. AB - The clinicopathologic correlation of three eyes with massive intraocular hemorrhage in patients receiving anticoagulant therapy is reported. All three patients were apparently predisposed because of antecedent disciform macular degeneration. The hemorrhage arose from the extrachoroidal neovascular vessels within the disciform lesions and caused rupture of the retinal pigment epithelium with massive intraocular hemorrhage. Because of the risk of vision-threatening intraocular hemorrhage, patients with exudative macular degeneration requiring anticoagulant therapy should be managed by both ophthalmologists and internists. PMID- 3342980 TI - Retests in static perimetry. AB - A large pool of visual field data measured with the JO program on the Octopus automated perimeter was used to compare the outcomes of simulated selective retests to those of global retests. Compared to global retesting, with selective retesting an increase in the mean sensitivity and a decrease in the number of pathological test locations were found on the average. We conclude that global retests should be preferred to selective ones so that the perimetric results are not falsified. PMID- 3342981 TI - Surface morphology of the human ciliary body during prenatal development. A scanning electron microscopic study. AB - The development of the ciliary body was examined by scanning electron microscopy in human embryos and fetuses with a gestation age of 9.5 to 24 weeks. During this period it was possible to follow up the main morphogenetical events, beginning with the appearance of the first radial folds up to the occurrence of ciliary processes with a rather adultlike arrangement. The ciliary processes observed during week 24 differed from those of the adult eye only by their dimensions and the lack of surface infoldings. A primitive pars plana could only be identified during week 24. The morphological basis for aqueous humor production is discussed. PMID- 3342979 TI - The fine structure of the developing human choriocapillaris during the first trimester. AB - In human embryos with a gestational age ranging from 6.5 to 13 weeks the development of the choriocapillaris was studied by electron microscopy. A continuous maturation process was observed over the whole period, which was most pronounced between weeks 6.5 and 9.7. During the earlier weeks, the endothelium appeared to be rather thick and contained many cytoplasmic vesicles; it was markedly flattened and less vesiculated than at week 9.7. This process was accompanied by an enlargement in the vascular lumina. Fenestrations directed towards the primitive Bruch's layer were found to be already present at week 7.2 but increased in number from week 9.7 to week 13. In the early weeks, basement membrane structures were present in small, discontinuous tufts of cloudy material adjacent to the endothelium. These structures became continuous at week 9.7 and increased in thickness towards week 13. In the earlier weeks, punctate junctions were seen. Beginning with week 9.7, adultlike tight junctions between the endothelial cells became observable. Pericytes were already present at week 6.5. It is suggested that both pericytes and endothelial cells are derived from the differentiating mesenchymal cells of the surrounding ocular stroma. PMID- 3342982 TI - Intraocular pressure changes in secondary positions of gaze in normal subjects and in restrictive ocular motility disorders. AB - One hundred normal Caucasian eyes and 29 eyes with restrictive disorders of ocular motility were studied in order to delineate intraocular pressure changes in secondary positions of gaze. Applanation tonometry was performed in the primary position and at an angle of 22 degrees. In patients with restrictive syndromes the changes of intraocular pressure in the secondary positions of gaze were significantly higher (p less than 0.0001) than in normal subjects. The range of variation in normal subjects was 0, +3 mmHg for supraduction and -3, +1 mmHg for abduction. Patients with restrictive syndromes showed changes between +1 and +15 mmHg for supraduction and between +3 and +10 mmHg for abduction. Results obtained in the two groups showed the existence of false negatives. This test is thus a practical and useful diagnostic tool, but its results must be evaluated cautiously. PMID- 3342983 TI - Development of the human sclera. A morphological study. AB - Differentiation of the sclera in human embryos and fetuses with a gestation age from 6.4 to 24.0 weeks was studied by light and electron microscopy. The developmental route was found to be anteroposterior and directed from inside outwards. Continuous cytological maturation begins anteriorly during week 7.2 with a loss of free ribosomes and polysomes and an increase in the amount of rough-surfaced endoplasmic reticulum (rER) and Golgi complex components. From the region of the future limbus, these cytodevelopmental events progress posteriorly. By week 13 there are no marked differences between anterior and posterior localization. The cytodevelopmental events directed from inside outwards were found to begin during week 7.2, with a marked increase in the addition of glycogen and lipid droplets in the choroidal half of the anterior scleral condensation and from there progressing to the outer (episcleral) half. With the beginning of week 10.9 no more differences were identified between the outer and the inner portions of the sclera. Portions of the ER denuded of ribosomes close to the plasmalemma were observed during the whole gestational period studied. The role of these structures and the involvement of the Golgi complex for the biosynthesis of collagen are discussed. In week 24, the diameter of the collagen fibrils had increased more than three times in comparison with week 6.4. Elastic microfibrils were found beginning with week 7.2, whereas the elastic deposits with central electron-translucent cores were characterized for the first time beginning with week 18. PMID- 3342984 TI - Family lifeline: bridging the miles. PMID- 3342986 TI - Adapting day care to the needs of adults with dementia. PMID- 3342985 TI - The home visit: field assessment of mental status impairment in the elderly. PMID- 3342988 TI - Response to "The factor structure of the Facts on Aging Quiz". PMID- 3342987 TI - The short-term effects of in-hospital respite on the patient with Alzheimer's disease. PMID- 3342989 TI - On Seefeldt's article on preschoolers visits to nursing homes. PMID- 3342990 TI - Religion and well-being in later life. PMID- 3342991 TI - Preventing elder abuse: identification of high risk factors prior to placement decisions. PMID- 3342992 TI - The prevalence of elder abuse: a random sample survey. PMID- 3342993 TI - Survival strategies of older homeless men. PMID- 3342994 TI - Perceived changes in grandmother-grandchild relations following a child's separation or divorce. PMID- 3342995 TI - Motivators and inhibitors of attitudes of filial obligation toward aging parents. PMID- 3342996 TI - Elderly psychiatric patient status and caregiver perceptions as predictors of caregiver burden. PMID- 3342997 TI - Preferences of older adults and experts for physical and architectural features of group living facilities. PMID- 3342998 TI - Nocturia in the elderly. PMID- 3343000 TI - Introduction to the role of oxygen radicals in myocardial ischemia and infarction. AB - There has been considerable interest over the past several years concerning the role of oxygen radicals in myocardial ischemia-reperfusion injury. The purpose of the following symposium will be to review recent advances in the understanding of oxygen free radical damage to the heart. Included in the symposium are descriptions of the biochemistry of free radicals and evidence of their direct toxic effects on the heart, as well as discussions concerning the effect of oxygen free radical scavengers on myocardial infarct size, the stunned myocardium, and cardiac preservation during surgery. PMID- 3342999 TI - Protection afforded by allopurinol in the first 24 hours of coronary occlusion is diminished after 48 hours. AB - Experiments were performed to test whether the reduction in infarct size afforded by allopurinol following 24 h of permanent coronary artery occlusion is sustained over the subsequent 24 h. A dog's coronary artery was occluded with an embolus followed by injection of radiomicrospheres into the left ventricle to mark the ischemic region and to measure regional blood flow. Dogs were sacrificed either 24 h or 48 hours after embolization. The infarcts were delineated by failure to stain with triphenyl tetrazolium chloride and the ischemic zones were visualized by autoradiography of the heart slices. Dogs in the treatment groups received 600 mg of allopurinol PO 18 h before surgery, and a 10 mg/kg IV bolus 15 minutes before embolization followed by constant IV infusion of 55 mg/kg/24 h until sacrifice. A close correlation in the control animals between the percent of the ischemic zone which infarcted and collateral blood flow was used to predict a nonintervention infarct size in each treatment animal. Allopurinol treatment caused 17.9 +/- 3.3% less of the risk zone to be tetrazolium negative after 24 hours of ischemia than that seen in untreated animals. Less allopurinol induced salvage was observed in the 48 hour drug group with only a 11.1 +/- 3.3% limitation in infarct size. Furthermore, the effect was inconsistent at 48 h with only 2 dogs showing salvage. We conclude that allopurinol delays but does not prevent infarction in the permanent occlusion model. PMID- 3343001 TI - Electrical correlate of circumferential contractions in human colonic circular muscle. AB - The role of myogenic electrical activity in the coordination of circumferential contraction of the human colon circular muscle was investigated. Five suction electrodes were placed (5-7 mm apart) on isolated rings of human colon and simultaneously electrical and motor activities were measured. In normal Krebs solution, the slow waves were not synchronised in most preparations studied. The electrical activities at the different recording sites were different with respect to slow wave frequency and amplitude, and amount of spiking activity. This resulted in irregular contractile activity. Cholinergic stimulation resulted in the development of a specific pattern of electrical activity: periodic slow wave activity with superimposed spiking activity which was synchronised over the length of the segment studied. This synchronised electrical activity resulted in regular phasic contractions at the frequency of the bursts of electrical activity (approximately 1/min). The response to carbachol was mediated by muscarinic receptors since it was blocked by atropine. The periodic activity in the continuous presence of carbachol was not the result of periodic input of neural activity as it occurred in the presence of TTX. Intrinsic properties of the muscle cells were responsible for the carbachol induced pattern of activity. The present study presents evidence that the electrical correlate of circumferential contractions is different in man compared with the most commonly studied animal models. It is a specific, stimulus induced pattern of myogenic activity. Its characteristics closely resemble those of a particular pattern of in vivo recorded activity referred to as the 'long spike bursts'. PMID- 3343002 TI - Young v adult cirrhotics: a prospective, comparative analysis of the clinical profile, natural course and survival. AB - In order to assess the frequency and profile of cirrhosis in the young, 169 consecutive patients with cirrhosis were studied. Sixty three (37%) patients of less than or equal to 35 years age were defined as young and the remaining 106 (63%) patients (greater than 35 years) as adult cirrhotics. Men predominated significantly (p less than 0.01) in the young cirrhotic group. The aetiology, the frequency of positive hepatitis B markers and initial clinical presentation were similar in the two groups. During the follow up period (30.6 +/- 29.7 months for the young and 25.8 +/- 21.7 months for the adult group), except for abdominal distension and pedal oedema which occurred significantly more often in the adult compared with the young cirrhotics, no difference was noted in the two groups. Twenty seven (39.7%) deaths (40% as a result of hepatic failure and 52% due to variceal bleeding) occurred in the young and 47 (44.3%) deaths (63.8% because of hepatic failure and 26% because of variceal bleeding) occurred in the adult cirrhotics during the follow up (difference NS). The five year survival (61.9% v 55.7%) and the probability of survival within the same Child's grade of liver disease were comparable. In both the groups, however, the probability of survival was significantly higher in Child's A compared with Child's B and C and in Child's B compared with Child's C grade of liver disease. Survival was not influenced by sex of the patient and aetiology of cirrhosis. Results of this prospective study indicate that cirrhosis is not uncommon in young adults. The aetiology, clinical presentation, natural history of the disease and the survival rates in young cirrhotics do not differ significantly from adult cirrhotics. PMID- 3343003 TI - Prospective study of malabsorption induced risk of gall stone formation in relation to fall in plasma cholesterol. AB - The relationship between cholesterol in plasma and risk of gall stone formation was investigated in 210 obese patients who underwent jejunoileal bypass surgery and were free of gall stone disease at the time. Among 185, successfully reexamined on average 19 months after surgery, 26 (14%) developed gall stones. The fall in plasma cholesterol after surgery exhibited a U-shaped relation to risk of gall stone formation with a minimum risk around the average fall (2.6 mmol/l). This was confirmed by multivariate logistic regression analysis (p less than 0.01) taking into account other possible determinants. The relation was not significantly dependent on weight loss or ratio between jejunum and ileum left in function. The study suggests that malabsorption induced fall in plasma cholesterol is related to risk of gall stone formation by two oppositely working mechanisms, one enhancing and one reducing the risk. PMID- 3343004 TI - Endoscopic sphincterotomy for common bile duct calculi in patients with gall bladder in situ considered unfit for surgery. AB - Endoscopic sphincterotomy (ES) was attempted in 106 patients with common bile duct (CBD) calculi and gall bladders present, who were considered unfit for surgery on the grounds of age and frailty alone (35%) and/or the presence of major medical problems (65%). Endoscopic sphincterotomy was successful in 105 patients (99%). Early ES related complications occurred in 21 patients (19.8%). Twelve hospital deaths occurred (11.3%), although this was due to biliary causes in only five (4.7%) and one of these was moribund on admission. Complications were more frequent in those in whom initial ES did not clear the common bile duct (30.4%) compared with those in whom this was (11.7%; p = 0.0164). The mortality was also greater in patients in whom there was no ERCP proof of CBD clearance (p = 0.01) unless operated upon. Twelve patients developed gall bladder complications (11.3%) including five with empyema (4.7%). Analysis of clinical, haematological, and biochemical factors together with ERCP findings showed that the only factor which had any value in predicting gall bladder complications was pre-existing cholangitis. The present series was compared with another using ES as a definitive procedure, and with a surgical series. Although there were significant differences in outcome, differences with respect to medical risk factors and the incidence of complications of CBD stones (jaundice, cholangitis, and acute pancreatitis) were striking. Further analysis of these factors may allow a clearer definition of patients most likely to benefit from either ES or surgery. PMID- 3343005 TI - Manometric measurement of human sphincter of Oddi length. AB - Length of biliary (CBD) and/or pancreatic (PD) sphincter of Oddi (SO) was measured during perendoscopic or intraoperative manometry in 21 control subjects and in 46 patients with biliary disease. When the high resting pressure (HPZ) and the phasic wave zone (PAZ) were considered, SO length was, in the control group, 9.5 +/- 0.5 mm (M +/- SE) and 9.4 +/- 0.6 mm at the level of the CBD-SO, and 7.7 +/- 0.6 mm and 6.9 +/- 0.5 mm at the level of the PD-SO. The physiological sphincter length appeared substantially shorter than the anatomical one, as reported in the literature. No significant differences were found between controls and patients with CBD stones. Endoscopic sphincterotomy without manometry reduced mean sphincter length length of the sphincterotomy was tailored to the manometric findings. Surgical partial sphincterotomy reduced sphincter length by only 46.7 +/- 10.3%. PMID- 3343006 TI - Synchronous small and large bowel cancer developing after pelvic irradiation. AB - This case report supports the belief that there is a causal relationship between therapeutic radiation and subsequent bowel malignancy. PMID- 3343007 TI - Non-cirrhotic portal hypertension with hypoxaemia. AB - Hypoxaemia and digital clubbing are rare but well recognised associations of hepatic cirrhosis with portal hypertension. We report the first European patient with idiopathic non-cirrhotic portal hypertension complicated by these features. Pulmonary physiological studies show the hypoxaemia to be the result of anatomical and physiological intrapulmonary shunting. PMID- 3343008 TI - Urological abnormalities in young women with severe constipation. AB - Anorectal and urodynamic studies were carried out in 10 young women with severe constipation and the results compared with those obtained in controls. The lowest volumes that provoked a desire to defecate (constipated 200 +/- 50 v controls 110 +/- 10 [mean +/- SEM] ml: p less than 0.05), and a desire to micturate (constipated 560 +/- 40 v controls 295 +/- 15 [mean +/- SEM] ml: p less than 0.001), were significantly greater in constipated patients compared with controls. The maximum tolerable rectal volume (380 +/- 30 v 290 +/- 20 [mean +/- SEM] ml: p less than 0.05) and the bladder capacity (720 +/- 50 v 540 +/- 10 [mean +/- SEM] ml: p less than 0.001) were also increased in the constipated subjects compared with controls. Electromyographic studies show failure of relaxation of the external anal sphincter (EAS) on attempted defecation in all 10 patients; and eight of these patients actually contracted their EAS when they strained to defecate, causing a functional outlet obstruction. Urodynamic studies showed normal urinary flow rates, normal detrusor pressures and normal radiology during voiding. Thus, these studies suggest that constipated patients have an increase in capacity and a reduction in sensitivity in the urinary bladder as well as in the rectum, but showed no evidence of obstruction to urine flow. PMID- 3343009 TI - Acidic colonic microclimate--possible reason for false negative hydrogen breath tests. AB - About 5% of normal subjects fail to produce increased hydrogen breath concentration after ingestion of the non-digestible carbohydrate lactulose (low hydrogen producers). The existence of low hydrogen producers limits the diagnostic use of hydrogen (H2) breath tests. We studied the effects of lactulose and of magnesium sulphate (MgSO4) pretreatment on stool-pH and on hydrogen exhalation after oral loading with lactulose or lactose in 17 hydrogen producers and 12 low hydrogen producers. In seven hydrogen producers acidification of stool pH by lactulose pretreatment (20 g tid) decreased hydrogen exhalation and three of seven (43%) became low hydrogen producers. In contrast, after pretreatment of eight low hydrogen producers with magnesium sulphate (5 g twice daily) all eight produced hydrogen after a lactulose load. Similarly four lactose intolerant low hydrogen producers had abnormal lactose hydrogen breath tests after MgSO4 pretreatment. MgSO4 pretreatment neither resulted in false positive lactose hydrogen breath tests in five lactose tolerant hydrogen producers, nor increased the hydrogen exhalation in five additional hydrogen producing controls after ingestion of lactulose. The results of these studies confirm that hydrogen production from lactulose decreases when the colonic pH is lower (lactulose pretreatment), and increases when colonic pH is higher (MgSO4 pretreatment). In low hydrogen producers the lacking increase of H2 exhalation after ingestion of non-digestible carbohydrates can be overcome by MgSO4 pretreatment, thus increasing the sensitivity of the test by avoiding false negative hydrogen breath tests in low hydrogen producers with disaccharide malabsorption or maldigestion. The underlying mechanism of this remarkable effect of MgSO4 pretreatment warrants further investigation. PMID- 3343010 TI - Low power interstitial Nd YAG laser photocoagulation in normal and neoplastic rat colon. AB - The effects of low power (1-2 Watts), long exposure (30-400 seconds), interstitial Nd YAG laser therapy on dimethylhydrazine induced rat colonic neoplasms and normal rat colon have been studied. After a single exposure with appropriate laser parameters, dimethylhydrazine induced rat colonic neoplasms underwent coagulative necrosis, sloughed off over a four day period, and left an ulcer which healed within 28 days. Inadequate laser energy resulted in incomplete tumour necrosis whilst excessive laser power or energy increased the likelihood of perforation. Treatment of normal colon with 1 Watt for 30 seconds or longer resulted in coagulative damage which healed by granulation. Mean colonic bursting pressures were significantly decreased one hour after treatment with 1 Watt for 75 or 100 seconds compared with untreated colon (p less than 0.05 and p less than 0.001 respectively) but not in colon treated with 1 Watt for 30 or 50 seconds. In animals treated with 1 Watt for 100 seconds mean bursting pressures were significantly lower than untreated animals when the animals were killed two, four, and seven days after lasering (p less than 0.001 in each case) but not in animals killed at 11, 17, or 21 days. The technique may be of value in the treatment of some inoperable colorectal cancers and sessile polyps in man. PMID- 3343011 TI - Sorbitol malabsorption in normal volunteers and in patients with coeliac disease. AB - Sorbitol is a hexahydroxy alcohol used as a sugar substitute in many dietetic foods and as a drug vehicle. Previous studies have suggested that sorbitol ingestion may be an additional cause of non-specific gastrointestinal distress. We evaluated sorbitol malabsorption in 30 healthy volunteers, seven patients with untreated coeliac disease and nine patients with coeliac disease on a gluten free diet, using a four hour H2 breath test. After ingestion of test solutions containing sorbitol 10 and 20 g and of four sweets (6.8 g sorbitol), 90%, 100%, and 62% of healthy volunteers, respectively had significantly raised H2 excretion, indicating malabsorption of sorbitol. Of all healthy subjects tested, 45% after 10 g, 100% after 20 g, and 50% after four sweets complained of symptoms of carbohydrate intolerance during the eight hours after sorbitol. After a 5 g dose given at concentrations of 2%, 4%, 8%, 16%, malabsorption was shown in 10%, 12%, 22%, and 43% of the healthy volunteers. Symptoms of intolerance at 5 g were experienced only at concentrations of 8% and 16%. Unlike healthy volunteers and coeliac patients on a gluten free diet, 100% of untreated coeliacs malabsorbed a 2% solution of 5 g sorbitol. These results show that malabsorption and intolerance of sorbitol may result from ingestion of doses and/or concentrations usually found in many foods and drugs; they underline the need to consider this as a possible and hitherto underestimated cause of gastrointestinal symptoms. PMID- 3343012 TI - Epidemiologic aspects of Crohn's disease: a population based study in Olmsted County, Minnesota, 1943-1982. AB - The overall age and sex adjusted incidence of Crohn's disease among Olmsted County, Minnesota, residents was 4.0 per 100,000 person-year in the period 1943 1982. Ileitis, ileocolitis, and colitis each accounted for about one third of the 103 incidence cases. Incidence rates were greater in woman than men, were higher in the urban portions of the county, and rose over time. Overall, the natural history of Crohn's disease in the community may be milder than that reported for patients at referral centres, as over half of all patients had no complications and only a third required surgery for Crohn's disease. Only one developed adenocarcinoma of the colon (relative risk = 2.0, NS). Survival was relatively unimpaired for the cohort, but Crohn's disease may have played a role in half of the deaths. The prevalence of Crohn's disease was 90.5/100,000 population on 1 January 1980. PMID- 3343014 TI - Changes in intestinal permeability and epithelial differentiation during inflammation in the rat. AB - We examined changes in gut permeability in a controlled model of inflammation produced in rats after infection with the nematode parasite, Nippostrongylus brasiliensis. The probe, 51Cr-EDTA, was injected into ligated loops of jejunum in vivo and recovery of radioactivity was measured in urine, kidney, and intact loop at five hours. Urinary recovery was significantly increased during the early (day 7) and acute (day 10) stages of the infection compared with values in control rats but subsequently returned to normal. Urinary clearance of the probe after iv injection was unaltered during infection. Villus atrophy occurred only at the stage, whereas crypt hyperplasia was evident at both the early and acute stages. The terminal ileum appeared normal and showed normal permeability when compared with controls. We conclude that permeability changes are local to the site of inflammation, are reversible after healing and may be related to an increase in the proportion of relatively undifferentiated epithelium. PMID- 3343013 TI - Combined sensory and motor deficit in primary neuropathic faecal incontinence. AB - Eleven patients with idiopathic faecal incontinence (IFI) and nine normal controls were studied with techniques of mucosal electrosensitivity and rectal distention for the quantitative assessment of anal and rectal sensation and with manometric and electromyographic tests for the assessment of anorectal motor function. The tests of motor function showed pelvic floor motor neuropathy in the patients with IFI, compared with controls, anal canal resting and voluntary contraction pressures were significantly (p less than 0.05, p less than 0.002) lower, pudendal nerve terminal motor latency and external anal sphincter fibre density were significantly (p less than 0.05, p less than 0.05) raised. The results of mucosal electrosensitivity (MES) disclosed a sensory deficit in the anal canal in patients with IFI, compared with controls, MES threshold was significantly (p less than 0.002) higher. Sensory thresholds to rectal distension were similar in the two groups. This study shows that sensory deficit of the anal canal occurs in combination with the motor neuropathy of the anal canal musculature in primary neuropathic faecal incontinence. PMID- 3343015 TI - Response of tuberculous stricture to antituberculous treatment. AB - Tuberculous infection of the gastrointestinal tract results in a variety of histopathological lesions. Some patients develop intestinal strictures and present with subacute intestinal obstruction. The treatment is controversial and vary from a trial of antituberculous drugs to early surgery:the response to medical therapy is not clear. To examine this issue the present prospective therapeutic trial was carried out on 39 patients with symptoms of bowel obstruction and radiological evidence of intestinal stricture. All patients were treated with conventional antituberculous drugs (streptomycin, rifampicin, and isoniazid) under close supervision. Thirty four (87%) patients completed the trial, five were lost to follow up. Thirty one (91%) of these showed significant clinical improvement:26 became completely symptom free, while the remaining five complained of only vague abdominal discomfort. Only three (8%) patients failed to respond to treatment and were subjected to surgery. Barium series were repeated in 23 of 31 who completed the treatment; the remaining eight refused further investigations. Complete resolution of the radiological abnormality was seen in 16 (70%) patients. In the remaining seven (30%) the stricture persisted; in two of these the treatment was continued for another year and both showed substantial radiological improvement. It is concluded that most patients with tuberculous strictures respond well to medical treatment and surgery should be resorted to only if drug therapy fails. PMID- 3343016 TI - Which peptic ulcer patients bleed? AB - In order to identify factors associated with peptic ulcers which present with bleeding rather than with pain, we have prospectively evaluated patient and endoscopic features in 139 consecutive patients presenting with acute bleeding and 74 presenting with pain found to have peptic ulceration at endoscopy. Patients with bleeding were more likely to have taken non-steroidal anti inflammatory drugs within the preceding four weeks (58% v 18%, p less than 0.001). They were older (66 v 51 years, p less than 0.001), more likely to have had a previous ulcer complication (21% v 1%, p less than 0.001), and to have an ulcer diameter greater than 20 mm (27% v 6%, p less than 0.05). The presence of one or more of these features in a patient who develops a peptic ulcer appears to be associated with a greater likelihood of presentation with a gastrointestinal haemorrhage. PMID- 3343017 TI - Effect of single and repeated intravenous doses of omeprazole on pentagastrin stimulated gastric acid secretion and pharmacokinetics in man. AB - Single intravenous doses of 10, 20, 40, and 80 mg and repeated once daily intravenous doses of 10 and 20 mg omeprazole induced a powerful and long lasting inhibition of pentagastrin stimulated gastric acid secretion (PAO) in healthy male volunteers. Single intravenous doses of 10, 20, 40, and 80 mg omeprazole inhibited PAO by 30% (p less than 0.01), 45% (p less than 0.01), 61% (p less than 0.01), and 80% (p less than 0.01), respectively when measured 1.5 h after dose, and by 20% (NS), 27% (NS), 36% (p less than 0.01) and 59% (p less than 0.01), respectively when measured 24 h after dose. Six days after repeated once daily intravenous doses of 10 and 20 mg omeprazole, PAO was inhibited by 63% (p less than 0.01) and 82% (p less than 0.01), respectively when measured 1.5 h after dose, and by 32% (p less than 0.01) and 43% (p less than 0.01), respectively when measured 24 h after dose. The inhibition of PAO by 10 mg administered intravenously as a single bolus injection was comparable with the inhibition by 20 mg as a single oral dose. Repeated once daily administration of 10 mg intravenously and 20 mg orally also resulted in comparable reductions in PAO. The reduction in PAO after repeated once daily oral administration of 20 mg was comparable with the effect of a single intravenous dose of 40 mg. Terminal half lives were short, but significantly (p less than 0.05) prolonged after a single intravenous injection of 80 mg. Repeated once daily intravenous administration of 10 and 20 mg did not result in prolongation of terminal half lives. It is concluded that intravenous administration of omeprazole causes a potent and long acting inhibition of pentagastrin stimulated gastric acid secretion in man. Its potency is augmented after repeated once daily administration. PMID- 3343018 TI - Biphasic nature of gastric emptying. AB - The existence of a lag phase during the gastric emptying of solid foods is controversial. It has been hypothesised that among other early events, the stomach requires a period of time to process solid food to particles small enough to be handled as a liquid. At present no standardised curve fitting techniques exist for the characterisation and quantification of the lag phase or the emptying rate of solids and liquids. We have evaluated the ability of a modified power exponential function to define the emptying parameters of two different solid meals. Dual labelled meals were administered to 24 normal volunteers. The subjects received meals consisting of either Tc-99m in vivo labelled chicken liver or Tc-99m-egg, which have different densities, and In-111-DTPA in water. The emptying curves were biphasic in nature. For solids, this represented an initial delay in emptying or lag phase followed by an equilibrium emptying phase characterised by a constant rate of emptying. The curves were analysed using a modified power exponential function of the form y(t) = 1-(1-e-kt)beta, where y(t) is the fractional meal retention at time t, k is the gastric emptying rate in min 1, and beta is the extrapolated y-intercept from the terminal portion of the curve. The length of the lag phase and half-emptying time increased with solid food density (31 +/- 8 min and 77.6 +/- 11.2 min for egg and 62 +/- 16 min and 94.1 +/- 14.2 min for chicken liver, respectively). After the lag phase, both solids had similar emptying rates, and these rates were identical to those of the liquids. In vitro experiments indicated that the egg meal disintegrated much more rapidly than the chicken liver under mechanical agitation in gastric juice, lending further support to the hypothesis that the initial lag in emptying of solid food is due to the processing of food into particles small enough to pass the pylorus. We conclude that the modified power exponential model permits characterisation of the biphasic nature of gastric emptying allowing for quantification of the lag phase and the rate of emptying for both solids and liquids. PMID- 3343020 TI - Combined pregnancy and starvation effects on rat tissue iron, zinc and copper contents. AB - The essential metal copper, zinc and iron content in starved virgin and pregnant rat tissue has been studied. The copper content of the whole rat, which was actually increased in pregnant rats, decreased in starved pregnant rats. The differences were significant in 19-day pregnant rats. The total copper content of the conceptus was not affected by starvation. Iron distribution and net tissue content showed the same pattern as that of copper. With regard to zinc, however, there was a decrease of its content associated with starvation in rat tissue. This decrease was statistically significant on the 21st day of gestation both in the mother and in fetuses, which marks a difference compared with the copper-iron pattern. It must be pointed out, however, that--with the significant exception of zinc--the maternal stores of the metals are enough to supply the fetus during starvation despite significant reductions in the maternal reserves. PMID- 3343019 TI - Epidemiological study of achalasia in children. AB - One hundred and twenty nine children under the age of 15 years were diagnosed as having achalasia in Britain and Ireland between 1976 and 1985 by 175 surgeons with an interest in paediatrics or oesophageal disease. The incidence in Eire was 0.31 cases/10(5) population/year and this was significantly higher than in England and Wales (0.1/10(5)/year), Scotland (0.06/10(5)/year/or Northern Ireland (0.02/10(5)/year). Details of age at diagnosis were only obtained for 36 of the 129 patients. The disease appeared to become commoner with increasing age but there is no evidence of a delay in diagnosis until early adulthood. Such a delay would not account for the apparent regional variations in incidence, as they have also been reported in adults. Southern Irish children are at greater risk of the disease than other children in the British Isles. PMID- 3343021 TI - Phospholipase C activity and phosphatidylinositol in amniotic fluid. A possible contribution of the fetus to the initiation of human parturition. AB - We investigated the mutual role between amniotic fluid and fetus in the mechanism of initiating human parturition. Phosphatidylinositol in amniotic fluid began to increase from around 30 weeks to 36 or 37 weeks of gestation and then gradually decreased toward term. On the other hand, we demonstrated phospholipase C activity in amniotic fluid, which increased toward term, and we also demonstrated the high phospholipase C activity in neonatal urine, which was 58-fold higher than that in amniotic fluid. The molecular weight of phospholipase C from neonatal urine was estimated to be 33,000 daltons. It was concluded that the fetus relates to onset of labor by producing arachidonic acid in amniotic fluid by the reaction between phosphatidylinositol from fetal lung and phospholipase C from fetal urine. PMID- 3343022 TI - Postcesarean section plasma fibronectin levels. AB - Decreases in plasma fibronectin levels following surgery and subsequent to trauma and sepsis have been previously reported. There have been no reports, however, regarding plasma fibronectin levels following cesarean section. Plasma fibronectin levels were followed for 3 days postpartum in 49 patients including cesarean section control patients, patients with cephalopelvic disproportion, pregnancy-induced hypertension, and endometritis. Cesarean section and cephalopelvic disproportion were not associated with a change in postpartum fibronectin levels. Pregnancy-induced hypertension and endometritis did show a significant increase (p less than 0.05) in plasma fibronectin levels. These levels are probably not decreased because of the large fibronectin pool in these otherwise healthy women. PMID- 3343023 TI - Serum levels of vitamin A, E, and selenium in women with lichen sclerosus of the vulva treated with etretinate. AB - Forty-six patients with Lichen sclerosus (Ls) of the vulva were treated with peroral etretinate for 3 months. The pretreatment serum levels of vitamins A and E, and selenium were measured. Etretinate therapy proved to be effective in the treatment of Ls; however, it did not affect the vitamin A status of the Ls patients. Vitamin E and selenium levels did not differ from the control values, nor did they have any prognostic value. PMID- 3343024 TI - Endometriosis in a patient with Rokitansky-Kuster-Hauser syndrome. AB - This case with Rokitansky-Kuster-Hauser syndrome and right ovarian endometriosis was previously presented as a proof against the transplant theory of Sampson. New operative findings showed a functioning endometrium in a right occult rudimentary horn and retrograde menstruation through the Fallopian tube with hematosalpinx, tubal endometriosis, right ovarian and appendicular endometriosis. PMID- 3343025 TI - The prognostic significance of X-ray changes at presentation and reassessment in patients with multiple myeloma. AB - The relationship between presenting skeletal X-ray findings and survival in multiple myeloma was assessed in 172 consecutive patients treated at this institute. All patients were investigated, treated and followed up according to one protocol. The shortest survival was seen in those with normal X-rays (3-year actuarial 11 per cent) and the longest in those with minimal lytic changes (3 year actuarial 44 per cent). Patients with osteoporosis alone and those with extensive lytic lesions had intermediate survivals of 32 per cent and 33 per cent respectively. Of the other major prognostic features only anaemia demonstrated a significant correlation with X-ray findings in terms of survival (p less than 0.001) suggesting that those with normal X-rays may have a more diffuse marrow involvement accounting for their poor prognosis. The response on bone X-rays in 102 patients who completed nine cycles of chemotherapy was also analysed. Patients with evidence of healing had a 3-year actuarial survival of 37 per cent, those with progression 36 per cent and those with stable X-rays 65 per cent (p less than 0.01). Normal bone X-rays at presentation and radiological evidence of healing following therapy appear to be bad prognostic signs in multiple myeloma. PMID- 3343026 TI - Comparative analysis of [3H]-thymidine labelling index and monoclonal antibody Ki 67 in non-Hodgkin's lymphomas. AB - The relation between the [3H]-thymidine labelling index (3H-Thy LI), which evaluates the S-phase cells, and the monoclonal antibody Ki-67 (MoAb Ki-67), which recognizes a nuclear antigen expressed during the cell cycle, was defined in 35 non-Hodgkin's lymphomas (NHL). Significantly higher median values of [3H] Thy LI and Ki-67-positive cells were observed for high-grade than for low-grade malignancy tumours according to the Kiel classification, but with wide and overlapping values for the two morphologic subgroups. A significant correlation was observed between [3H]-Thy LI and Ki-67-positive cells (P less than 0.0001; r = 0.62). However, the ratio between the two cell kinetic variables on individual tumours was not constant. It sharply increased with decreasing [3H]-Thy LI values and was much higher in low-grade NHL than in high-grade NHL. Follow-up studies are needed to establish the role of the tumour growth fraction as evaluated by MoAb Ki-67 as a prognostic indicator in NHL. PMID- 3343027 TI - Follicular non-Hodgkin's lymphoma in Hong Kong Chinese: a retrospective analysis. AB - Follicular lymphoma is relatively rare in Hong Kong Chinese. Fifty-two patients with follicular lymphoma were reviewed. The histology was nodular lymphocytic poorly differentiated (NLPD) in 75 per cent, nodular mixed (NM) in 21 per cent and nodular histiocytic (NH) in 4 per cent. Our patients appeared to have a higher proportion of NLPD and a lower proportion of NM lymphoma than the western series. Fifty patients were analysed excluding the two patients with NH lymphoma. They had a median age of 50 and a male to female ratio of 0.92. Seventy-two per cent of them presented with asymptomatic lymph node enlargement. Twenty per cent had B symptoms and 32 per cent bulky tumour. Twelve per cent had stage I disease, 2 per cent stage II, 30 per cent stage III and 56 per cent stage IV. A high incidence of bone marrow involvement (48 per cent of all patients) was found. All seven stage I-II patients responded to involved-field radiotherapy alone and none of them has relapsed. The 43 stage III-IV patients were treated with chemotherapy without deferral and a majority of them received CVP (51.1 per cent) or chlorambucil alone (34.9 per cent). The complete response rate of stage III-IV patients was 81 per cent and 26 per cent of the complete responders relapsed. The 5-years disease-free survival (DFS) and overall survival of all patients (stage III and IV) were 50 per cent and 65 per cent respectively. The DFS curve showed a pattern of continuous relapses. Stage III patients appeared to have a better complete response rate, a lower relapse rate and superior disease-free survival than stage IV patients but the differences did not reach statistical significance. However, the overall survival of stage III patients was significantly better than stage IV patients (p less than 0.02). Other factors including sex, age, presence of bulky tumour, B symptoms, histologic subtypes and the chemotherapeutic regimes did not significantly affect their prognosis. PMID- 3343029 TI - Temporal and spatial factors in diethylstilbestrol-induced squamous metaplasia of the developing human prostate. AB - The effects of exogenous estrogen on the developing human prostate were examined in human fetal prostatic rudiments grown for 1 month as subcapsular renal grafts in athymic male nude mice treated with diethylstilbestrol (DES). Prostatic rudiments grown in untreated (control) hosts exhibited normal ductal morphogenesis, growth, and secretory cytodifferentiation. Squamous metaplasia was observed rarely in controls (2 of 22). Conversely, squamous metaplasia was observed in the prostatic utricle and urethra of all 17 specimens grown in DES treated hosts. Proximal and distal prostatic ducts exhibited DES-induced squamous metaplasia in 13 and 12 of the specimens, respectively. When present, metaplastic changes were mild in the distal ducts. The distribution and intensity of metaplasia were related to the age of the specimen during the period of DES exposure. In specimens grown in DES-treated hosts to a gestational age equivalent of 16.5 weeks or less, squamous metaplasia was only seen in the prostatic utricle and urethra; however, in specimens grown to a gestational age equivalency of 17 weeks or more, squamous metaplasia was observed in the prostatic ducts as well. The nonuniform distribution of estrogen-induced squamous metaplasia within the developing prostatic ductal system emphasizes a regional and age-dependent susceptibility to exogenous estrogens in proximal ductal areas (near the urethra) as compared with distal ductal regions of the developing human prostate. PMID- 3343028 TI - Experience with the Portacath. AB - Fifty Portacaths have been inserted in patients undergoing prolonged outpatient chemotherapy, most for haematological disease. Twenty-one are still working at a median duration of 12 months (range 1-27) and a further 15 were functioning normally at the time of the patients death (median survival 6 months). Four functioning Portacaths have been removed, three suspected of causing septicaemia and one believed erroneously to have occluded. Ten have ceased to function and nine of these have been removed. The causes of these failures are nearly all avoidable and are discussed in detail; many occurred early in our experience. With careful attention to detail and with management by trained and interested staff, the Portacath is a safe and reliable device for intermittent vascular access. PMID- 3343030 TI - Retraction of bioprosthetic heart valve cusps: a cause of wide-open regurgitation in right-sided heart valves. AB - Most failures of bioprosthetic heart valves in children are due to stenosis secondary to thrombus, calcific deposits, or tissue ingrowth. Valve failures due to regurgitation typically involve cuspal detachment, tears, or perforations. We present four cases of prosthetic valve regurgitation in children caused by cuspal retraction without stenosis and describe the morphologic findings related to the valves at autopsy or explantation. A mononuclear cell and giant cell response to the cusps of the valve was a striking finding in one patient. PMID- 3343031 TI - Benign lesions mimicking malignant tumors of the esophagus. AB - Three cases of benign lesions which mimicked malignant tumors of the esophagus are described. In all three cases, two inflammatory pseudotumors and one case of diffuse leiomyomatosis, the clinical presentations, radiologic features, and gross pathologic findings led to the mistaken diagnosis of carcinoma at thoracotomy. The benign nature of the processes was recognizable only on microscopic examination. Although most benign tumors of the esophagus are localized solitary lesions that are easily distinguished from carcinoma, occasionally benign conditions may present as infiltrative, ulcerated mass lesions. Inflammatory pseudotumor and diffuse leiomyomatosis should be included in the differential diagnosis of esophageal malignancies. PMID- 3343032 TI - Observer variation in the diagnosis of dysplasia in Barrett's esophagus. AB - The potential value of biopsy surveillance of patients with Barrett's esophagus for dysplasia is diminished by a lack of agreement on the diagnostic criteria for dysplasia. In a preliminary consensus conference, experienced gastrointestinal pathologists from four medical centers agreed on criteria for a five-tiered histologic classification of dysplasia in Barrett's esophagus--negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and intramucosal carcinoma. Eight morphologists in the four centers tested the criteria for interobserver agreement by examining a set of coded slides that had been chosen to include some especially difficult interpretative problems in all five histologic classifications. Interobserver agreement of 85 and 87% was achieved in successive reviews when the combined group of high-grade dysplasia and intramucosal carcinoma was compared with the combined group of low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia. Comparison of other groups yielded less agreement. For example, negative for dysplasia could be distinguished from all other diagnoses with an interobserver agreement of 72%. We conclude that experienced gastrointestinal morphologists can diagnose high-grade dysplasia and intramucosal carcinoma with a high degree of agreement and thus can detect those patients who may need immediate rebiopsy or esophageal resection. Either further refinement of histologic criteria or alternate diagnostic methods will be needed to achieve the reproducible diagnosis of indefinite changes and low-grade dysplasia. This is important because patients with such changes theoretically merit closer endoscopic surveillance. PMID- 3343033 TI - Mucinous cystadenoma of the ovary with stromal luteinization and hilar cell hyperplasia during pregnancy. AB - A 32-year-old woman was delivered of a healthy, full-term infant by cesarean section, at which time a large ovarian cyst was removed. The cyst proved to be a mucinous cystadenoma with prominent luteinization of the stroma subtending the epithelium and with numerous foci of hyperplastic Leydig cells in the cyst wall and ovarian hilum. These hormonally induced changes must be recognized in order to avoid mistaking them for invasive epithelial components. PMID- 3343034 TI - Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long term follow-up study of cancer risk. AB - A cohort study of women with ductal involvement by cells of atypical lobular hyperplasia (DIALH) revealed an incidence of 1.4% in benign biopsy specimens. When combined with diagnostic lobular unit alterations of atypical lobular hyperplasia (ALH), a consequent risk of invasive carcinoma of 6.8 times that in the general population was found. This relative risk for women with ALH and DIALH approaches the risk for lobular carcinoma in situ, whereas the risk for ALH with or without DIALH is 4.3 and the risk for ALH without DIALH is reduced to 2.7. Only definitive changes of DIALH with an insinuated characteristic population of cells between attenuated luminal cells and basement membrane should be so diagnosed. DIALH in association with lobular alterations that are borderline with regard to a diagnosis of lobular carcinoma in situ will increase the certainty that a medically meaningful increased risk for subsequent invasive cancer is indicated. PMID- 3343035 TI - Lead arthritis and lead poisoning following bullet wounds: a clinicopathologic, ultrastructural, and microanalytic study of two cases. AB - Bullet wounds causing lead synovitis in the wrist and knee are reported in two patients, one of whom also developed clinical plumbism. Very high lead levels in the synovial fluid are believed to be responsible for toxicity changes that occurred in the synovium and bone. Ultrastructurally, these alterations included the formation of nuclear lead inclusions, dilation, and degranulation of the rough endoplasmic reticulum and deposition of crystalline precipitates in the matrix of the mitochondria in macrophages, osteoclasts, and synoviocytes, as well as the development of cytoplasmic lead inclusions in osteoclasts. Energy dispersive x-ray elemental analysis (EDXEA) indicated that the nuclear inclusions contained only lead, whereas precipitates within the mitochondria and elsewhere in the cytoplasm were composed of complexes containing lead, calcium, and phosphorus. Similarly constituted extracellular complexes were incorporated into newly formed trabecular bone laid down as a physiologic response to the bullet lodged within the wrist bones. This bone subsequently exhibited defects in bone resorption, which were characterized by depressed osteoclastic function and a unique lesion termed incomplete osteocytic osteolysis. The genesis of this latter lesion is uncertain. The sequestration of the partially degraded bone fragments containing lead complexes into the marrow and eventually into the joint spaces and synovium permitted the recycling of bone lead, and this may have played an important role in inducing clinical plumbism in one of the patients in this study. PMID- 3343036 TI - Early pancreatic duct adenocarcinoma. AB - A 68-year-old Japanese woman presented with complaints of appetite and weight loss. Early pancreatic duct adenocarcinoma was diagnosed by endoscopic retrograde cholangiopancreatography (ERCP), which revealed partial obstruction of the main pancreatic duct. Pancreatoduodenectomy with lymph node dissection was performed. Macroscopically, no pancreatic tumor was detected. Histologically, the pancreatic lesion showed continuous changes consisting of duct epithelial cell hyperplasia, carcinoma in situ, and invasive carcinoma. Immunohistochemical stains for carcinoembryonic antigen and CA19-9 were positive in cancer cells. PMID- 3343037 TI - Mycobacterium avium-intracellulare and adrenal insufficiency in AIDS. PMID- 3343038 TI - Computerized interactive morphometry. PMID- 3343039 TI - Rehabilitation counseling. PMID- 3343040 TI - Safer sex. PMID- 3343041 TI - Maintaining mental wellness. PMID- 3343042 TI - The myths and realities of psychiatric nursing or I feel guilty when I just sit and talk. PMID- 3343043 TI - The importance of assertive behavior. PMID- 3343044 TI - The forgotten angels: women nurses of the Vietnam war. PMID- 3343045 TI - Hemodynamics of the carotid artery after vasodilation in essential hypertension. AB - We performed simultaneous noninvasive measurements of common carotid artery and brachial artery hemodynamics in nine normal subjects and 10 subjects with sustained essential hypertension. In hypertensive subjects, brachial artery blood flow and forearm vascular resistance were in the normal range while carotid artery blood flow and carotid artery resistance were decreased and increased, respectively. The most important findings were the changes in the internal caliber of large arteries. Although the brachial and carotid artery diameters of hypertensive subjects were measured for the same level of mean arterial pressure, brachial artery diameter was significantly increased and carotid artery diameter was strictly normal as compared with values found in normal subjects. To assess whether carotid artery circulation could influence the baroreceptor reflex response to arteriolar vasodilation, carotid artery and brachial artery hemodynamics were measured in immediate succession in normotensive and hypertensive subjects before and after oral administration of cadralazine, a dihydralazine derivative. After cadralazine treatment, carotid artery tangential tension decreased in hypertensive subjects, and the changes were significantly correlated to the increase in heart rate. A similar correlation was found in normal subjects, but it was reset toward higher heart rates. These results indicate that the carotid artery does not behave like the brachial artery in response to a chronic increase in blood pressure. This behavior indicates intrinsic alterations of the arterial wall and might be involved in the resetting of the carotid baroreceptor reflex. Carotid artery circulation could play a role in hypertension by modulating the carotid baroreceptor mechanisms involved in the response to drug-induced arteriolar vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343046 TI - The differential effect of aldosterone and dexamethasone on pressor responses in adrenalectomized rats. AB - The effect of selective glucocorticoid or mineralocorticoid replacement on pressor responses to angiotensin I and II and norepinephrine was studied in adrenalectomized rats given high salt intake. Four groups were prepared by 1) adrenalectomy only (n = 5); 2) adrenalectomy plus aldosterone, 6 micrograms/24 hr i.p. (n = 5); or 3) adrenalectomy plus dexamethasone, 10 micrograms/24 hr i.p. (n = 5), using miniosmotic pumps; and 4) sham adrenalectomy (controls; n = 5). Plasma corticosterone was undetectable in all three adrenalectomized groups. Plasma aldosterone concentration was similar in aldosterone-replaced and sham operated controls. Pressor responses to various doses of angiotensin I, angiotensin II, and norepinephrine were determined in unanesthetized, undisturbed rats. Compared with both control and dexamethasone-replaced rats, pressor responses to all three agonists were significantly reduced in both nonreplaced adrenalectomized and aldosterone-replaced groups. Comparing the ratios of the pressor responses to angiotensin I and angiotensin II in the four groups over the entire dose range suggests that a greater fraction of injected angiotensin I was converted to angiotensin II in nonreplaced adrenalectomized rats than in the other three groups. We conclude that glucocorticoid action markedly contributes to the systemic pressor effect of angiotensin and norepinephrine. However, glucocorticoid deficiency does not impair in vivo conversion of angiotensin I to angiotensin II. PMID- 3343047 TI - Evaluation of medial hypertrophy in resistance vessels of spontaneously hypertensive rats. AB - The role of smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in medial hypertrophy of mesenteric resistance vessels of 107- to 111-day-old spontaneously hypertensive rats (SHR) was examined using a combination of morphometric, biochemical, and immunological techniques. Mesenteric arteries were classified on the basis of branching order for comparative purposes. Branch level I vessels were those that directly enter the jejunal wall, while Branches II to IV represented more proximal vessels; Branch IV vessels were those that branch from the superior mesenteric artery. Medial hypertrophy was assessed in perfusion fixed vessels by morphometric evaluation of medial cross-sectional area and smooth muscle content. Medial cross-sectional area and smooth muscle content were significantly increased in larger (Branches III and IV) but not smaller (Branches I and II) mesenteric resistance vessels of SHR compared with control normotensive Wistar-Kyoto rats (WKY). Smooth muscle cell hypertrophy and hyperploidy were evaluated in isolated cells obtained by enzymatic dissociation of mesenteric resistance vessels. Approximately 80% of the cells in these preparations were identified as smooth muscle cells using a smooth muscle-specific isoactin antibody. Feulgen-DNA microdensitometric evaluation of isolated cells showed that polyploid cells were present in mesenteric resistance vessels but at very low frequencies, and no differences were apparent between SHR and WKY. Likewise, no differences in cellular protein content or relative smooth muscle cell size (i.e., area profile) were observed between cells obtained from SHR and WKY vessels. These results demonstrate that the increase in medial smooth muscle content observed in larger mesenteric resistance vessels of SHR cannot be accounted for by smooth muscle hypertrophy and hyperploidy, inferring that hyperplasia must be present. Results indicate that studies of the initiating mechanisms for medial smooth muscle hypertrophy in SHR resistance vessels, at least relatively early in hypertension, should focus on examination of factors that induce true cellular proliferation rather than hypertrophy and hyperploidy. PMID- 3343048 TI - Antibacterial activity of recombinant murine beta interferon. AB - Recombinant murine beta interferon was protective and therapeutic for mice against Listeria monocytogenes infection in vivo. The recombinant murine beta interferon caused enhanced H2O2 release by macrophages in vivo, but not in vitro. PMID- 3343049 TI - Relationship among cell wall composition, stage of growth, and virulence of Nocardia asteroides GUH-2. AB - The clearance and organ distribution of virulent Nocardia asteroides GUH-2P and the avirulent mutant GUH-2AI at different stages of growth was determined after intravenous inoculation into BALB/c mice. The mutant differed significantly from the parent strain in its ability to survive and grow within the murine host. Since the mutant GUH-2AI had a very different colonial morphology compared with GUH-2P, it was believed that cell surface components might be affected by the mutation that resulted in the loss of virulence. Therefore, cell walls of both GUH-2P and GUH-2AI at different stages of growth were prepared and their composition determined. There were growth-stage-dependent changes in the composition of the cell walls that appeared to correlate with concurrent alterations in virulence; however, the overall chemical composition of the cell wall of the mutant (GUH-2AI) was not significantly different from that of the parent strain (GUH-2P). Both strains demonstrated significant modifications in fatty and mycolic acid composition at different stages of growth. Furthermore, the specific composition of C54 mycolic acids was very different in virulent log phase cells compared with less-virulent stationary-phase cells, and the avirulent mutant lacked a C54:3 mycolate that was prominent in the virulent log-phase GUH 2P. Thus, C54:3 mycolic acid represented 2.5% of the cell wall (dry weight) in log-phase GUH-2P, but it was undetectable in the walls of GUH-2AI at the stationary phase of growth. These results suggest that certain mycolic acids are associated with virulence. PMID- 3343050 TI - Effects of Clostridium difficile toxins A and B in rabbit small and large intestine in vivo and on cultured cells in vitro. AB - Clostridium difficile is recognized as the major cause of antibiotic-associated colitis. C. difficile produces two toxins, A (enterotoxin) and B (cytotoxin), that are implicated in the pathogenesis of the colitis. We examined the dose responses, time course, and synergism of these two toxins in ligated rabbit intestinal loops and in tissue culture. In rabbit small intestinal loops, toxin A caused histologically demonstrable intestinal tissue damage as early as 2 h. The secretory response greater than or equal to 8 h was similar to that of a cholera toxin control. The effect of toxin A on tissue damage or secretion was seen even if toxin was removed after 5 min. Purified toxin A caused significant net accumulation of sodium, chloride, potassium, and total protein and slightly increased osmolality of the fluid content at 6 h; these effects were similar to those caused by crude C. difficile culture filtrates containing toxins A and B. Crude C. difficile toxin caused fluid accumulation with a delayed time course in the rabbit large intestine, and in contrast to its effect in small intestine, crude toxin caused net accumulation of bicarbonate and increased pH. In tissue culture, toxin A caused a rounding up of CHO and T-84 colonic carcinoma cells. A monoclonal antibody (PCG-4) that has no effect on tissue culture cytotoxicity with toxins A and B completely inhibited the secretory and tissue-damaging effects in the intestine. Toxins A and B were synergistic in the gut only at high doses of toxin B (greater than or equal to 10 micrograms/ml), and they were additive in tissue culture. The cytopathic effect in tissue culture was not consistently associated with trypan blue uptake. The cytopathic effect of toxin A in tissue culture did not appear to involve inhibitable Ca2+-dependent or prostaglandin synthesis pathways or intact microfilament or microtubule function for its activity and was not inhibited by reducing or lysosomotropic agents. Our results suggest that toxins A and B have independent and distinct effects in vivo and in vitro. PMID- 3343051 TI - Susceptibility of HRS/J mice to listeriosis: dynamics of infection. AB - Congenitally hairless HRS/J homozygous (hr/hr) mice as well as phenotypically normal littermates (hr/+) were found to exhibit unusual susceptibility to infection with Listeria monocytogenes with 50% of the animals dying within a 10 day period (LD50) at an infecting inoculum approaching 200 microorganisms. In marked contrast to the outbred CD-1 strain as well as other Listeria-susceptible mice, HRS/J hosts are virtually incapable of limiting infection with virulent Listeria. The dynamics of infection reveal early uncontrolled bacterial growth within the peritoneal cavity, followed by a sharp increase of bacterial load in the spleen of both HRS/J homozygotes and heterozygous littermates. Spleen indices obtained for mutant mice indicate substantial splenomegaly which parallels the onset of infection in that organ. Assessment of the exudate population within the peritoneal cavity during infection indicates that HRS/J mice produce an early sustained influx of polymorphonuclear leukocytes while exhibiting a diminished macrophage inflammatory response. Additionally, it was shown that the mutant strain expresses significant increases in the total number of recoverable peritoneal leukocytes in response to other phlogistic stimuli. PMID- 3343052 TI - Lacteal immunity to enteric cryptosporidiosis in mice: immune dams do not protect their suckling pups. AB - The susceptibilities of passively immunized principal and nonimmunized control suckling mice to orogastric challenge with Cryptosporidium parvum oocysts were compared. Principals were suckled by dams that had recovered from C. parvum infection. Controls were suckled by dams reared free of C. parvum infection. Principals and controls were equally susceptible to challenge. Principals were susceptible even when their dams were hyperimmunized by oral and parenteral booster inoculations with C. parvum oocysts. Immune dams produced serum antibody against C. parvum, while nonimmune dams did not. Anti-cryptosporidia immunoglobulin G (IgG) and IgA were demonstrated in whey extracted from the stomachs of principals that had suckled immune dams but not in whey extracted from the stomachs of controls. It was concluded that passive lacteal immunity is not an efficient means of protection against cryptosporidiosis in mice. As in other coccidian infections, protective immunity against cryptosporidiosis may depend more on immune cells than on antibody. PMID- 3343053 TI - Response of a Streptococcus sanguis strain to arginine-containing peptides. AB - For dental plaque organisms such as Streptococcus sanguis, the ecological importance of the ability to utilize arginine as an energy source has been established in previous studies. The present investigation was undertaken to determine the ability of a strain of S. sanguis to process unsubstituted arginine containing peptides. The organism was grown under glucose-limited conditions in a chemically defined medium, and peptide was added to washed, resting cells in a pH stat at pH 7.0. Filtrates taken at appropriate time intervals were assayed for peptide, free amino acids, and metabolites. Irrespective of the position of the arginine residue, all peptides tested were attacked, although those that possessed a C-terminal arginine (including a tetrapeptide) were processed at a faster rate than were those in which arginine was N terminal. However, C-terminal arginine was cleaved only slowly from a peptide containing 24 residues. In each case, most of the released arginine was converted to ornithine via the arginine deiminase pathway. Such peptidase activities appeared to occur at or near the cell surface and were probably constitutive. It was found that the organism grew in chemically defined medium containing arginine that was present solely in the form of a tripeptide, and also that a strain of S. mutans possessed only a limited ability to attack arginine-containing peptides and was unable to utilize the released arginine. PMID- 3343054 TI - Small-intestinal factors promote encystation of Giardia lamblia in vitro. AB - Bile salts and fatty acids stimulated differentiation of cultured Giardia lamblia trophozoites into water-resistant cysts at the slightly alkaline pH of the small intestinal lumen. Maximum encystation occurred at pH 7.8. Thus, specific small intestinal factors may influence encystation in vivo as well as in vitro. PMID- 3343055 TI - Inhibition by estrogens of conidium-to-yeast conversion in the fungus Paracoccidioides brasiliensis. AB - Conidia produced by Paracoccidioides brasiliensis are inhibited by mammalian estrogens in their in vitro conversion into yeast-form cells. This was demonstrated with four different isolates. In these experiments, conversion was reduced to 10.7 and 34.4% of the control values by 17-beta-estradiol at 10(-6) and 10(-8) M, respectively. At the same concentrations, the synthetic estrogen diethylstilbestrol was slightly less inhibitory. In contrast, other sex hormones and analogs, i.e., testosterone, 17-alpha-estradiol, tamoxifen, and hydroxytamoxifen, had no effect on conidium-to-yeast conversion. Previous studies have shown that estrogens similarly inhibit mycelium-to-yeast-form transition in P. brasiliensis. Conidia, and not mycelial fragments, are believed to be the natural infectious propagules. These findings with conidia support the hypothesis that estrogens, affecting the initial host-parasite interactions by suppressing conversion to the parasitic form of the organism, are, at least in part, responsible for the greater resistance of females to paracoccidioidomycosis. PMID- 3343057 TI - The premature demise of DVI pacing. PMID- 3343056 TI - Serological response to the outer membrane lipoprotein in animal brucellosis. AB - The presence of antibodies to Brucella outer membrane lipoprotein was investigated in cattle and rams. Low but significant amounts of antibody were detected in sera from B. abortus-infected cattle and from B. ovis-infected rams which had developed epididymitis. Strain-19-vaccinated cattle also showed a weak albeit transient antibody response. PMID- 3343058 TI - Endomyocardial fibrosis in a white girl with sero-positive juvenile rheumatoid arthritis. AB - A white girl with sero-positive juvenile rheumatoid arthritis was subsequently found to have endomyocardial fibrosis. We believe that these two rare conditions were not causally related. PMID- 3343059 TI - Tetralogy of Fallot with aortopulmonary window. AB - A patient with tetralogy of Fallot associated with aortopulmonary window has been documented. The association was found in one case out of 350 consecutive cases of Fallot's tetralogy evaluated cineangiographically. Since tetralogy of Fallot may be completely masked by the aortopulmonary window it is suggested that a right ventricular angiogram should be obtained in all patients with an aortopulmonary window. PMID- 3343060 TI - Reliability of echocardiography in the detection of metastatic malignant pericardial masses. AB - Pericardial metastasis is a rare localization of a malignant neoplasm. We report a 28-year-old man with metastatic spread of an epithelial thymoma into the pericardium. This in turn compressed the heart with induction of exertional dyspnea, hepatomegaly, chest pain and increased jugular venous pressure. All these features occurred in the absence of significant hemodynamic impairment. Echocardiography revealed an intrapericardial mass at the level of the left ventricular free wall. Surgical removal of this pericardial neoplasm produced a rapid improvement in clinical status. Ultrasonography, therefore, is a reliable noninvasive method for the diagnosis of cardiac impairment due to a pericardial metastatic mass. PMID- 3343061 TI - Increase of pulmonary vascular resistance during cold provocation in patients with variant angina. AB - This study was performed to evaluate pulmonary vascular reactivity in patients with angiographically documented coronary vasospasm. Right heart catheterization was performed in 8 subjects with vasospastic angina without evidence of Raynaud's phenomenon: heart rate, systemic and pulmonary arterial pressure as well as cardiac output were determined at rest, during cold provocation and after 20 minutes recovery. Data were obtained both before and during treatment with nifedipine. During cold provocation pulmonary vascular resistance was elevated significantly (P less than 0.02 compared with baseline); systemic vascular resistance tended to increase; nifedipine blunted both vasoconstrictor effects. Our results indicate an abnormal vascular response of the pulmonary arteries to cold provocation in patients with symptomatic coronary artery spasm and suggest a primary vasospastic disorder with coronary and pulmonary manifestation. PMID- 3343062 TI - Myocardial infarction in pregnancy. AB - Three cases of myocardial infarction occurring in the third trimester of pregnancy are presented. The method of delivery in each case was individualised with no maternal or fetal mortality. Each patient had significant risk factors for coronary arterial disease or thrombosis. One patient had normal coronary arteries demonstrated at coronary arteriography. PMID- 3343063 TI - The resting surface electrocardiogram as a predictor of future hypertension. AB - Resting supine and post-provocation (dynamic exercise, isometric exercise and cold pressor) levels of blood pressure were measured in 80 normotensive offspring of normotensive parents (control) and 55 normotensive offspring of parents with essential hypertension. The surface electrocardiogram (including conventional twelve leads, posterior chest leads, right-sided chest leads and bipolar precordial leads) was also recorded in all subjects. Twenty-eight offspring of parents with essential hypertension had their resting and/or post-provocation blood pressure above the upper limit of standard deviation in age- and sex matched control group. Flat or upright T waves, with either S waves less than 0.2 mV, or S/R ratio less than 2, or T waves equal to or higher than the accompanying R waves in lead V4R, could identify these potential hypertensives with nearly 90% specificity and nearly 75% sensitivity. The criterion had been derived, however, by analysis of the data achieved retrospectively. Therefore, the exact discriminating value of this criterion can be assessed only by a long-term prospective study. PMID- 3343064 TI - Magnetic resonance imaging of the heart for determination of ejection fraction. AB - In 28 patients with various cardiac diseases we compared ejection fractions obtained by magnetic resonance imaging in a single oblique slice with monoplane ventriculography in the right anterior oblique projection, the latter serving as the standard. Also, results were evaluated for clinical relevance and relation to image quality. The correlation between the two techniques was moderate (r = 0.65). According to our standardized limits for clinical relevance, insufficiently correlating ejection fractions were obtained in 14 patients. In 8 of these patients this was attributed to poor endocardial edge detection. Edge detection problems were more frequently encountered by imaging with echo-time 20 msec than with echo-time 32 msec. Other causes for mismatching of the obtained ejection fractions are discussed. It is concluded that determination of ejection fraction by single slice magnetic resonance imaging should not be used for clinical application. Improvement can be expected by using a contiguous slicing technique, a longer echo-time in the spin-echo pulse sequence, or in due course by application of newly developed fast-imaging pulse sequences. PMID- 3343065 TI - Developmental aspects of atrioventricular septal defects. AB - Three human embryos with an atrioventricular septal defect were studied. Their morphology was compared with that of 67 autopsy specimens, in which particular attention was paid to the septal attachments of the bridging leaflets. The malformed embryos showed deficiency of the inlet component of the ventricular septum. They had distinct superior and inferior bridging leaflets, which were nearly completely muscular. Myocardial undermining had taken place at two independent sites but had not been able to lead to the formation of a valve of mitral morphology. Normal delamination of myocardium to form the leaflets could not continue directly below the aortic root because the rim of the inlet septum had a more apical position. From this, we conclude that the deficiency of the inlet septum is the cause of the typical morphology of the left valve in these hearts. The role of endocardial cushion tissue is probably restricted to glueing together myocardial structures, thus determining the variable septal attachment of the bridging leaflets in atrioventricular septal defect. PMID- 3343066 TI - Doppler echocardiographic comparison of haemodynamic results of one- and two stage anatomic correction of complete transposition. AB - Eighteen children who had single-stage and 18 who had two-stage anatomic correction of complete transposition between the ages of 1 week and 3 years (mean 6.5 months) were investigated with pulsed and continuous wave Doppler ultrasound. Peak mitral flow velocities showed no significant difference from normal after single-stage correction, but were significantly higher than normal after two stage correction (P less than 0.05). Peak tricuspid flow velocities were significantly higher than normal in both groups (P less than 0.02 and P less than 0.001). There was no significant difference in pulmonary artery flow velocities between the two groups, which were means (SD) of 214 (84) cm/sec after single stage and 179 (87) cm/sec after two-stage repair. Peak velocities in the ascending aorta were within normal limits after single-stage correction, but were lower than normal in the two-stage group (P less than 0.02). Mild aortic regurgitation was detected in 22% of single-stage and 55% of two-stage patients (P = 0.043, 2P = 0.085). Both types of repair are associated with higher peak tricuspid flow velocities than normal and have a similar incidence of mild supravalvar pulmonary stenosis. Mitral flow velocities are higher than normal only after two-stage correction. Velocities in the ascending aorta are lower than normal and the incidence of mild aortic regurgitation appears to be increased after two-stage repair, probably due to dilatation of the aortic root following banding of the pulmonary trunk. PMID- 3343067 TI - Coronary-to-bronchial artery anastomosis complicated with myocardial infarction. AB - A patient with bronchiectasis had an inferolateral myocardial infarction. Coronary arteriography revealed a large anastomosis from the left circumflex artery to the left lower lobe bronchial arteries. The relationship between the patient's myocardial infarction and possible "coronary steal" is discussed. PMID- 3343068 TI - Aortic atresia with a solitary and indeterminate ventricle. AB - A male infant having aortic atresia and double inlet to a solitary and indeterminate ventricle, presented a clinical picture of "hypoplastic left heart syndrome". Haemodynamic consequences are described and comparison made to other types of aortic atresia. Cross-sectional echocardiography was found to be reliable in determining both atrioventricular and ventriculo-arterial connections in the presence of aortic atresia and a solitary ventricle. PMID- 3343069 TI - The problem of deception within medical science. PMID- 3343070 TI - Left bundle branch block--an elementary catechism. PMID- 3343071 TI - Spatial quantitative vectorcardiography in aortic stenosis: correlation with hemodynamic findings. AB - Thirty-four patients with hemodynamically documented valvar aortic stenosis without congestive heart failure were studied by the corrected Frank lead system vectorcardiography, with special emphasis on the angular characteristics of spatial R max to define the severity of the lesion. Spatial QRS-T angle demonstrated a highly significant correlation with the peak left ventricular systolic pressure (r = 0.72, P less than 0.001) and a significant correlation with peak transvalvar aortic gradient (r = 0.49, P less than 0.01). Furthermore, all patients with a QRS-T angle of more than 90 degrees had significant aortic stenosis (TVG greater than or equal to 50 mm Hg). The peak left ventricular systolic pressure and transvalvar aortic gradient also demonstrated a significant negative correlation with azimuth angle (r = -0.36 and -0.34, respectively; P less than 0.05) and a positive correlation with spatial R max magnitude (r = 0.38 and 0.41, respectively; P less than 0.05). There was no correlation between elevation angle of spatial R max and left ventricle systolic pressure or transvalvar aortic gradient. Our study indicates that spatial quantitative vectorcardiographic angular characteristics, particularly spatial QRS-T angle, may be a useful adjunct to other noninvasive techniques to assess the severity of valvar aortic stenosis. PMID- 3343072 TI - Torsade de pointes and ventricular flutter-fibrillation following spontaneous cerebral subarachnoid hemorrhage. AB - Five cases (3.8%) in a series of 132 patients with spontaneous subarachnoid hemorrhage, studied by 24-hour Holter monitoring, presented with ventricular tachycardia of torsade de pointes variety. In all cases, the arrhythmias were observed within 24 hours after the bleeding. The QTc interval was prolonged more than 0.55 sec, and hypokalemia of less than 3.5 mEq/liter was present in all patients. The clinical status was not significant. Torsade de pointes occurred in comatose patients (3 cases) as well as in alert patients (2 cases). The arrhythmia was reversed by therapy in 3 patients, one of whom survived while 2 died due to cerebral damage. Our observations confirm the presence of life threatening ventricular arrhythmias in the acute phase of subarachnoid hemorrhage. Continuous electrocardiographic monitoring is therefore advisable in view of its potential role in alerting to the need for treatment. PMID- 3343073 TI - Detection of left ventricular ischemia during atrial pacing: simultaneous assessment by echocardiography and invasive hemodynamic measurements. AB - The ability of cross-sectional echocardiography to detect myocardial ischemia induced by atrial pacing was assessed during cardiac catheterization in 11 patients with coronary arterial disease. Angina pectoris was precipitated in all patients with increase in left ventricular end-diastolic pressure after pacing by 5 +/- 6 (mean +/- standard deviation) mm Hg (P less than 0.01). Regional left ventricular dysfunction occurred during pacing in all patients as determined by quantitative echocardiographic assessment of wall motion. Simultaneously, systolic reduction in parasternal short-axis area decreased (from 42 +/- 13 to 28 +/- 9%, P less than 0.01) with concomitant decrease in ejection fraction as determined in the apical four-chamber view (from 49 +/- 5 to 40 +/- 8%, P less than 0.01). In conclusion, echocardiography may detect pacing-induced myocardial ischemia through detection of regional and global left ventricular dysfunction. Inadequate regional perfusion may be indicated by echocardiography even in patients without apparent evidence of ischemia as determined by invasive hemodynamic measurements. PMID- 3343074 TI - Exaggerated systolic blood pressure response to exercise: a normal variant or a hyperdynamic phase of essential hypertension? AB - This study examines the left ventricular function (by first-pass radionuclide angiography with a multicrystal gamma camera) at rest and during symptom-limited upright exercise in 27 normal subjects (group 1), 25 normotensive subjects with exaggerated systolic blood pressure response to exercise (greater than 200 mm Hg) (group 2) and 25 patients with essential hypertension and no associated coronary artery disease (group 3). There were no significant differences between groups 1 and 2 in exercise tolerance, heart rate, total vascular resistance, left ventricular ejection fraction and end-systolic volume. However, the exercise cardiac index and systolic blood pressure were significantly higher in group 2 (P less than 0.02). Compared to group 3, the subjects in group 2 had higher exercise heart rate (P less than 0.0001), cardiac index (P less than 0.0001), systolic blood pressure (P less than 0.0001) and left ventricular ejection fraction (P less than 0.0001) and lower exercise total vascular resistance (P less than 0.0002) and end-systolic volume (P less than 0.01). Thus, the hemodynamic profile in subjects with exaggerated systolic blood pressure response to exercise differs from that of essential hypertension; it may represent a supernormal response. PMID- 3343075 TI - Exercise-induced precordial ST-segment depression in prior inferior myocardial infarction with single-vessel disease; with special reference to its mechanisms and distinction from multi-vessel disease. AB - We investigated the mechanisms of exercise-induced precordial ST-segment depression on the electrocardiogram in prior inferior myocardial infarction with single-vessel disease and attempted to differentiate the ST-segment depression between single- and multi-vessel disease. Subjects included three groups: group Ia (n = 11), inferior myocardial infarction with single-vessel disease that showed no precordial ST-segment depression; group Ib (n = 7), inferior myocardial infarction with single-vessel disease accompanied by precordial ST-segment depression; and group II (n = 10), inferior myocardial infarction with multi vessel disease. The subjects underwent 12-lead exercise electrocardiography, stress Tl-201 myocardial imaging and stress radionuclide ventriculography. Exercise-induced precordial ST-segment depression observed in group Ib was associated with large infarction and infarction extending into the inferoseptal wall of the left ventricle on myocardial image. On stress ventriculography, worsening of the septal wall motion was more frequently observed in group Ib than in group Ia. Coronary arteriography revealed a higher rate of rich collateral vessels to the infarcted zone in group Ib than in group Ia. When we compared the diagnostic ability for detecting multi-vessel disease in prior inferior myocardial infarction, although sensitivity was not different among three tests, both exercise electrocardiography and radionuclide ventriculography had poor specificity and predictive value compared to stress Tl-201 myocardial imaging. Thus we concluded that exercise-induced precordial ST-segment depression observed in prior inferior myocardial infarction with single-vessel disease should reflect a peri-infarctional ischemia located in the inferoseptal wall of the left ventricle, and that stress Tl-201 myocardial imaging is the most accurate method for diagnosing multi-vessel disease in prior inferior myocardial infarction. PMID- 3343076 TI - Competition of coronary arteries and ventriculo-coronary arterial communications in pulmonary atresia with intact ventricular septum. AB - Pulmonary atresia with intact ventricular septum can be complicated by the presence of large ventriculo-coronary arterial communications which disturb normal myocardial perfusion. In the selection of patients for surgery the presence of these communications provides an additional problem. On the basis of previous cineangiocardiographic study, we performed a histopathological study of 16 cases. Twelve presented with ventriculo-coronary arterial communications and four only showed myocardial sinusoids. A tripartite right ventricle was seen in the latter group but not exclusively. It is shown that subepicardial coronary arterial pathology is exclusively present in cases with ventriculo-coronary arterial communications although not solely at a connection site between a communication and an artery. The affected coronary artery is itself focally abnormal and hypoplastic and can be blocked or even absent. The interruption of such an artery can also occur after birth and not necessarily at a site of connection with a communication. This implies that infants with communications either already have a coronary circulation partly or completely dependent on ventriculo-coronary arterial communications at birth or can develop such a condition in time. This hazard to myocardial perfusion, often compromised by a large "steal" from the aorta to the right ventricle, limits the choice of surgical procedures. PMID- 3343077 TI - Balloon dilation of subaortic stenosis due to a thick fibrous shelf. AB - A young patient with discrete subaortic stenosis due to a thick fibrous shelf was subjected to transcatheter balloon dilation. The outcome of the procedure and its probable mechanism is discussed. PMID- 3343079 TI - Cross-sectional echocardiographic demonstration of biventricular thrombus. AB - Nine months following extensive myocardial infarction, a 60-year-old man presented with intermittent right heart failure. Cross-sectional echocardiography demonstrated biventricular thrombi, the right ventricular thrombus being very close to the tricuspid valve and possibly interfering with its function. Post mortem examination confirmed the echocardiographic findings. PMID- 3343078 TI - Magnetic resonance and echocardiography in the investigation of cardiac tumour in an infant. AB - An intracardiac tumour in an asymptomatic female infant was diagnosed by means of echocardiography and magnetic resonance. The natural history of this pathology in patients showing no symptoms of cardiac involvement is still unknown. The development of these modern diagnostic techniques, however, has made it easier to carry out longitudinal follow-up studies aimed at obtaining useful information about the prognosis and growth potentialities of these tumours. PMID- 3343080 TI - Dissecting aneurysm of a right-sided descending aorta with a left-sided aortic arch. AB - A 66-year-old man presented with myocardial infarction. Chest X-ray showed a large mediastinal mass. Aortic dissection was suggested by a past history of chest trauma, but the mass was in a very atypical site. Dissection of an abnormally placed right-sided descending aorta was confirmed by computed tomography. The aortic arch lay on the left side. This rare combination of congenital and acquired heart disease led to diagnostic difficulty. PMID- 3343081 TI - Misuse of forensic hypnosis: a hypnotically elicited false confession with the apparent creation of a multiple personality. PMID- 3343082 TI - Misuse of hypnosis in sexual contexts: two case reports. PMID- 3343083 TI - Posthypnotic amnesia, the hidden observer effect, and duality during hypnotic age regression. PMID- 3343084 TI - EEG asymmetry during covert mental activity and its relationship with hypnotizability. PMID- 3343085 TI - Promoting health among teenagers. AB - The need for health promotion programmes geared to adolescents has never been more acute. Today's youth lives in a "throw away society" characterized by an impermanence of both objects and human relations--which works counter to traditional health values and practices. The result has been a rise in teenage drug-addiction, suicide, abortion, delinquency and alcoholism. How can we make nurses and health services more accessible to adolescents? Below, Angela Gillis describes a model for adolescent health promotion and provides some practical suggestions for dealing more effectively with this age group. PMID- 3343086 TI - Tapping health care resources: a comparison of US and UK strategies. AB - The United Kingdom and the United States are both facing dramatic changes in health care delivery and resource allocation, brought about by advanced technology, limited financial (and in some cases human) resources and conflicting values regarding the right to health care. The differences and similarities of their health care systems provide a favourable research environment for comparing how the two countries acquire and allocate their respective health care resources. For the purpose of such a comparative study, two sites were selected, the London region of Central Thames and the US city of Energytown (only the names are fictitious). Central Thames is representative of an English region in size, administrative structure and health services; Energytown is representative of an oil city in the US Midwest. National policy, reductions in health care funds and size make the areas amenable to a comparative study. PMID- 3343087 TI - Measles vaccination timing: finding the right age. AB - Measles is one of the most ubiquitous and persistent of human viruses. Before generalized vaccination programmes, measles was widely considered an unavoidable disease of children and a part of growing up. This passive acceptance of measles is still held today, particularly in the developing world where measles complications are so severe that the disease is viewed not only as a primary cause of disability and death but as a precursor and aggravator of those great killers of children: pneumonia, diarrhoea and malnutrition (12). Of vital importance is the age at which it is best to vaccine children against measles. Using tropical Africa as a geographic model, this article briefly examines the evolution of minimum age policies since the measles control programmes in Africa began in the 1960s and the expected outcome, and gives recommendations for future research. PMID- 3343088 TI - Joint WHO/UNICEF statement on vitamin A for measles. PMID- 3343089 TI - Nurses, nursing and women. AB - WHO's project on women as providers of health care, in which many countries, agencies and individuals have been involved in various capacities, has given birth to a book entitled "Women as Providers of Health Care". While presenting an objective picture of the situation of women who dispense health care--formally or informally, within the family and community--around the world, the book tries to stimulate thought on the subject of women's contribution to health and how it can be enhanced. The chapter on "Nursing and the condition of women", condensed below, identifies some of the major issues hindering nursing education and practice. It is intended to lead to a better and broader understanding of the problems faced by women as health care providers. PMID- 3343090 TI - Metastatic dissemination of B16 melanoma: evidence that metastases can result from nonspecific trapping of disseminated tumor cells. AB - Spontaneous metastasis from tumor transplants of two representative mouse B16 melanoma clones, G3.5 and G3.12, was examined experimentally to determine whether initial dissemination to the lungs, or secondary systemic spread from established lung metastases, resulted from organ-specific tropism or from nonspecific trapping of circulating tumor cells in capillary beds. In parabiosed mice, subcutaneous tumors metastasized extensively within hosts, but guests remained metastasis-free except following the rare involvement of the parabiotic junction during secondary spread. Intrasplenic tumor transplants metastasized to the liver, whereas intrarenal transplants metastasized to the lungs, reflecting patterns of venous drainage. Subcutaneous implants of neonatal lung and kidney in the flank opposite from the site of tumor initiation acquired metastases only during secondary systemic spread, and there was no evidence of organ selectivity. Metastases from various organs, and derived cell lines, when transplanted subcutaneously grew into tumors that initially metastasized exclusively to the lungs. These results indicate that both initial and secondary metastases of these B16 melanoma transplants occurred by nonspecific trapping of tumor cells in the first capillary bed encountered. In contrast, organ colonization following intravenous injection of tumor cells frequently proceeded beyond the first capillary bed. PMID- 3343091 TI - Difference in motile behavior between lymphoma variants with different invasive and metastatic capabilities. AB - The motile behavior of two tumor cell variants of the murine BW 5147 lymphosarcoma line, displaying different metastatic capabilities, was analyzed. When placed on top of a confluent monocellular layer of fibroblastic cells, the nonmetastatic lymphoma cells did not carry out any appreciable translocation or shape modification, whereas the metastatic cells displayed intense pseudopodal activity and performed positional shifts. Both these aspects of cell motility were approached through quantitative assays, demonstrating a highly significant difference between the two variant lines. In addition, the metastatic cells were shown to penetrate underneath the fibroblastic monolayer, whereas the nonmetastatic cells were unable to invade. We suggest that the difference in motile behavior is at the basis of the different invasive potencies of the variants. Since in vitro monolayer invasion assays mimic the extravasation of blood-borne cells, we further speculate that in this particular model system, cell motility is the discriminating property that determines whether disseminated tumor formation will occur after intravenous injection of either cell line. PMID- 3343092 TI - The influence of Fluosol-DA on the occurrence of lung metastases in Lewis lung carcinoma and B16 melanoma. AB - The development of lung metastases from subcutaneously implanted tumors or the development of lung nodules from intravenously injected tumor cells are model systems for metastases formation. Animals bearing subcutaneous Lewis lung tumors (50-100 mm3) were treated with a single dose of Fluosol-DA followed by 1 h of breathing carbogen or maintenance in air. Their lungs were examined for metastases 25 or 40 days after tumor cell implantation. Treatment with Fluosol-DA and carbogen or air breathing reduced by almost 4-fold the number of lung metastases seen. The addition of Fluosol-DA with air or carbogen breathing to treatment of the tumor-bearing limb with 20 Gy reduced the number of lung metastases by 2-fold compared to radiation treatment alone. If Fluosol-DA was administered immediately before or up to 3 days prior to an intravenous challenge with Lewis lung tumor cells, there was a 2- to 3-fold reduction in the number of lung nodules formed. Fluosol-DA administered immediately before or up to 4 days prior to B16 melanoma cells caused a 2- to 3-fold reduction in the number of lung nodules observed. The vascular endothelial cell monolayer adhesion assay was used to test the effects of prior exposure to Fluosol-DA on the attachment of radiolabelled B16 melanoma cells in vitro. There was a trend toward increasing attachment of B16 cells to the endothelial monolayer with prior exposure to increasing concentrations of Fluosol-DA; however, this difference did not reach statistical significance. PMID- 3343093 TI - Adsorption of proteins from artificial tear solutions to contact lens materials. AB - A series of polymers and copolymers of 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) were synthesized in order to find surfaces that would adsorb minimal amounts of protein. The adsorption of albumin, lysozyme and immunoglobulin G from a three-way mixture of these proteins in isotonic buffered saline to the polymers was measured using 125I-labeled proteins. Apparently high protein uptake on copolymers rich in HEMA was found to be due to sorption of unbound 125I by the polymers. 125I sorption by the polymers was minimized by dialysis of the protein solution to remove unbound 125I iodide and inclusion of 0.01 M sodium iodide to block uptake of residual 125I iodide. Using these improved protocols, minimal total protein uptake was observed on copolymers containing 50% or more HEMA. The majority of adsorbed protein on all p(MMA-HEMA) polymers was albumin. Total protein uptake was greatest on pMMA. Commercial contact lenses composed of copolymers of HEMA and N-vinyl pyrrolidone (NVP) or acrylamide (AAm) adsorbed small amounts of all proteins whereas copolymers of methacrylic acid (MAAc) and HEMA adsorbed much larger quantities of lysozyme. These results indicate that protein uptake by contact lens materials varies greatly with polymer composition. Artifactually high "adsorption" can occur if precautions are not taken to prevent uptake of unbound 125I. PMID- 3343094 TI - Tear film osmolarity and ocular surface disease in two rabbit models for keratoconjunctivitis sicca. AB - We report the natural history of keratoconjunctivitis sicca (KCS) in two rabbit models. The first one (full KCS model) was created by closing the lacrimal gland excretory duct, and removing the nictitating membrane and harderian gland. We created the second one (lacrimal gland duct only [LGDO]-KCS model) by closing the lacrimal gland excretory duct. Although tear film osmolarity was abnormally high in both models, it was higher in the full KCS model. Decreases in corneal epithelial glycogen and in conjunctival goblet cell density, and morphological abnormalities of the conjunctiva correlated with increases in tear film osmolarity and duration of disease. PMID- 3343095 TI - Recurrent HSV-1 corneal epithelial lesions induced by timolol iontophoresis in latently infected rabbits. AB - Herpes simplex virus type 1 (HSV-1) ocular shedding and recurrent corneal epithelial lesions were assessed following ocular iontophoresis of 0.01% timolol at 0.8 mAmp for 8 min for 3 consecutive days in 17 rabbits latently infected with HSV-1 strain McKrae. The collection of ocular tear film for the detection of HSV 1 ocular shedding and the slit lamp biomicroscopic evaluation for HSV-1 epithelial lesions began on day 4 after the first iontophoresis and continued for 7 consecutive days. The tear film was collected on a Dacron swab with care being taken to avoid swabbing the corneal epithelium. The observed HSV-1 lesions were characterized as deep punctate lesions, dendritic lesions and geographic epithelial defects. The ratio of total days of eyes exhibiting HSV-1 epithelial lesions to the total number of observation days was 113/235 (48%). There were 46 punctate lesions, 27 dendritic lesions and 40 geographic epithelial defects. The ratio of positive swabs to total swabs was 77/235 (33%). Of the 113 positive lesion days, 65 (58%) were associated with a positive swab. Of the 77 positive swabs, 65 (84%) were associated with an epithelial lesion. Of the 122 negative lesion days, 110 (90%) were associated with a negative swab. Of the 158 negative swabs, 110 (70%) were associated with no epithelial lesions. By chi-square analysis, there was a significant association between HSV-1 swabs and HSV-1 lesions (P less than 0.001). These results demonstrate that ocular iontophoresis of timolol induces both HSV-1 ocular shedding and recurrent HSV-1 corneal epithelial lesions in rabbits latently infected with HSV-1 strain McKraw. PMID- 3343096 TI - Development of a biopolymeric keratoprosthetic material. Evaluation in vitro and in vivo. AB - Based on the results of in vitro and in vivo experiments, we have determined that the optimal material for the central transparent portion of a perforating keratoprosthesis is a polyvinyl alcohol copolymer hydrogel. The material supports the maintenance and growth of corneal epithelium in vitro as shown by population doublings and transmission electron microscopy. Discs preseeded with epithelial cells were cultured in vitro and transplanted into rabbit corneas. The proliferation of these cells in vivo was demonstrated using 3H-thymidine. Other experiments showed that the preseeded cells not only migrated from the central disc onto the peripheral rim of the host cornea but also that host peripheral epithelial cells migrated onto the anterior surface of the disc. The experiments described in this paper demonstrate that corneal epithelial cells preseeded onto hydrogel discs and transplanted into rabbit corneas remain adherent and are capable of proliferating. PMID- 3343097 TI - Evidence against the role of rhodopsin in rod outer segment binding to RPE cells. AB - The possible role of rhodopsin in the binding and phagocytosis of rod outer segments (ROS) by cultured bovine retinal pigment epithelial (RPE) cells was studied using both quantitative phagocytosis assays and electron microscopy. In inhibition studies an immunoaffinity purified 2-39 N-terminal rhodopsin glycopeptide, a synthetic 1-16 peptide analogue of rhodopsin and purified, unsealed ROS disc membranes were found to be ineffective in inhibiting the binding of 125I-labeled ROS to RPE cells. A two-fold excess of unlabeled intact ROS, however, inhibited 125I-labeled ROS binding to RPE cells by over 40%. In another series of experiments, rhodopsin on the surface of fixed ROS was densely labeled with gold-dextran particles conjugated to an N-terminal-specific (rho 4D2) rhodopsin monoclonal antibody or its F(ab')2 fragment in an effort to block binding and phagocytosis by RPE cells. As visualized by both transmission and scanning electron microscopy using secondary and backscatter electron imaging, these antibody-gold-dextran-labeled ROS were effectively phagocytized by RPE cells. These results provide compelling evidence that rhodopsin in the ROS plasma membrane does not function as the ligand for recognition by RPE cells. PMID- 3343098 TI - Shielding properties of laser-induced plasmas in ocular media irradiated by single Nd:YAG pulses of different durations. AB - Shielding of laser pulses by plasmas generated in ocular media has been experimentally investigated using single Nd:YAG laser pulses of different durations, ranging from several nanoseconds (ns) to a few tens of picoseconds (ps), both in saline solution and extracted calf vitreous. At the respective threshold radiant exposures for breakdown in saline (259 mJ/cm2 for 7 ns, 20.5 mJ/cm2 for 220 ps and 4.7 mJ/cm2 for 30 ps pulses) the single pulse energy transmission is found to be about 74% for 7 ns, 55% for 220 ps and 50% for 30 ps, thus showing that shielding of laser-induced plasmas is more effective for shorter pulses than for longer pulses. Moreover, the decrease in transmission with increasing radiant exposure is faster in the picosecond case than in the nanosecond case. These results show that direct irradiation of the retina is, to some extent, present especially near threshold. In the case of picosecond pulses, a comparison with published results indicates that shielding between subsequent pulses in a train is likely to occur only to a very limited extent. PMID- 3343099 TI - Clinical suppression and amblyopia. AB - In individuals with abnormal binocular vision, such as strabismics and anisometropes, it is common for all or part of one eye's view to be suppressed so binocular confusion and diplopia are eliminated. We examined the relation between the depth of suppression (the amount by which the monocular contrast increment threshold for an eye was elevated by stimulation in the contralateral eye) and the degree of amblyopia (difference in monocular contrast thresholds for the two eyes). There was a significant negative correlation between suppression and amblyopia, so that clinical suppressors with no amblyopia exhibited deep suppression (ie, large threshold elevation) while observers with amblyopia exhibited weaker or no suppression. This negative correlation was found when the two eyes viewed orthogonally oriented contours as well as identically oriented contours. These results suggest that when an eye is amblyopic there is no longer a need for strong suppression of that eye by the contralateral eye. PMID- 3343100 TI - Visual fields of infants assessed with a new perimetric technique. AB - The visual field of normal infants was assessed using a perimeter with LED stimuli and a forced-choice observation procedure. Central fixation was elicited by four central, pulsing LEDs and maintained with the aid of auditory stimuli. Field extent was derived from the four-alternative, forced-choice judgments of an adult who observed the infant's eye movements to peripherally illuminated LEDs. The binocular visual field of infants, ages 6-7 months, was similar to that of adults tested with the same apparatus. Area of the infants' binocular field was 93% that of the adults'. However, the infants' monocular fields were smaller than those of adults, averaging 74% of the adults' monocular field area. This may have been due to the distracting effect on infant behavior of the adhesive patch used for monocular testing. The visual fields of a young patient with hydrocephalus illustrate the potential clinical utility of this new perimetric technique for infants at risk of field defects. PMID- 3343101 TI - Differences in adaptation of tonic accommodation with refractive state. AB - It has recently been demonstrated that intersubject variations in tonic (dark focus) levels of accommodation are related to corrected refractive state (McBrien and Millodot, 1987). The aim of the present study was to investigate the effect of sustained visual tasks on the tonic level of accommodation in different refractive groups. Eleven hyperopes, 16 emmetropes, ten early onset myopes and ten late onset myopes had their tonic accommodation measured with the objective infrared optometer Canon Autoref R-1 before and after a 15 min sustained visual counting task. The post-task tonic accommodation level was monitored for 15 min to assess the decay rate of any observed task-induced changes in tonic accommodation. Subjects repeated the experimental procedure for four task locations (6 m, pre-task tonic position, 37 cm and 20 cm). Late onset myopes showed significant positive (myopic) changes in their tonic level of accommodation at both near viewing distances, which showed no evidence of decay during the 15 min post-task monitoring period. Hyperopes, however, underwent transient "counteradaptive" decreases in their tonic level of accommodation after sustained near viewing. Emmetropes and early onset myopes showed little change in tonic levels at the two near distances. Differences between groups were also obtained at tonic and far viewing distances. Post-task changes in tonic accommodation demonstrated only a weak negative correlation with pre-task tonic accommodation levels at each task distance. It is proposed that the observed differences in adaptation of tonic accommodation among refractive groups may be related to variations in autonomic innervation of the ciliary muscle. PMID- 3343102 TI - The effect of simulated scotomas on visual search in normal subjects. AB - A simulated scotoma was stabilized on the fovea of 23 normal human subjects while they searched for acuity targets in arrays of non-targets. Search time doubled with a 20 min arc scotoma, and eye fixation duration increased by about 15% when compared to no-scotoma control conditions. Search difficulty was graded by adjusting acuity target size, search element density and contrast. Search time and eye fixation duration generally increased with display difficulty in no scotoma conditions. Results are discussed in terms of sensory loss and motor disruption due to the simulated scotoma. The simulated scotoma method may be useful in studying adaptation to visual field loss in patient populations where the size, position and severity of the scotoma can be controlled. PMID- 3343103 TI - Evaluation of poor performance and asymmetry in the Farnsworth-Munsell 100-hue test. AB - A statistical method for the analysis of errors on the Farnsworth-Munsell 100-hue test is introduced. The extent of asymmetry of errors are summarized by two indices, I1 and I2, derived from Fourier analysis of the error scores for the individual caps. The second index, I2, describes the (bipolar) color axis; the first index, I1, describes (monopolar) asymmetry of performance. The present analysis differs from previous approaches based on Fourier analysis of the errors in two ways: (1) a procedure is introduced which corrects the indices I1 and I2 for the biases that result from the segmentation of the test into four boxes; (2) statistics for the significance of I1 and I2 are derived by a Monte Carlo procedure, which properly handles the complex interdependence of individual error scores for each cap. PMID- 3343104 TI - The lipids of chalazia. AB - The tissue contents of chalazia taken from five individuals were extracted for lipids and analyzed by TLC and GLC. Lipids found were sterol esters 9%, wax esters 0%, triacyl glycerols 4%, free cholesterol 11%, free fatty acids 2%, unidentified nonpolar material 3%, ceramides 7%, cerebrosides 3%, phosphatidyl ethanolamine 12%, phosphatidyl choline 20%, sphingomyelin 4%, lysolecithin 4%, unidentified polar material 18.0%. GLC of the sterol esters gave peaks corresponding to the C14, C16, C18 and C20 normal fatty acid esters of cholesterol. The free fatty acids were also of the normal kind. Thus, the lipids of chalazia contents show little similarity to the lipids of the meibomian gland. The latter has a large component of sterol esters and wax esters. Also the fatty acids of all the meibomian gland ester lipids have significant amounts of iso- and anteisobranching in contrast to the chalazia lipids. Chalazia lipids more closely resemble the lipids of membranes of phagocytic cells with a large cholesterol content. PMID- 3343105 TI - Effect of cholinergic drugs on outflow facility after ciliary ganglionectomy. AB - In cynomolgus monkeys, resting total outflow facility was unaltered 1 and 6 or more months after ciliary ganglionectomy (CG) or postganglionic ciliary neurectomy (PCN). Intraocular pressure (IOP) was decreased in the denervated eye 1 week and 1 month after surgery, but returned to normal after 6 or more months. Although baseline facilities were comparable in CG/PCN and fellow control eyes 6 or more months after surgery, even maximal intracameral doses of pilocarpine did not increase outflow facility in previously denervated eyes, while a normal facility increase occurred in fellow control eyes. However, both previously denervated and fellow control eyes exhibited a large facility increase to both submaximal and greater than maximal intracameral doses of eserine. PMID- 3343106 TI - Rod ERG diurnal rhythm in some patients with dominant retinitis pigmentosa. AB - Five patients with dominant retinitis pigmentosa who were monocularly entrained to a 14 hr light: 10 hr dark cycle showed an abnormal diurnal rhythm in the rod electroretinogram of the entrained eye. These patients as a group showed larger than-normal reductions in b-wave sensitivity 1.5 hr and 8 hr after light onset relative to other times of day. The findings raise the possibility that these patients have an abnormality in rod photoreceptor function associated with the process of outer segment renewal. PMID- 3343107 TI - Donor age influences on the success of retinal grafts to adult rat retina. AB - The rat retina can be successfully grafted within a long time period which extends into the first 2 weeks of postnatal life. Postnatal grafts taken 1-2 days (PN 1-2) after birth demonstrate no significant differences in their ability to form successful grafts. However, grafting success begins to diminish gradually starting between PN 2-4 and reaches a low point in organization and survival by PN 14. PN 21 grafts rapidly degenerate by 1 to 2 days after transplantation. Although early postnatal retinal tissue can be successfully grafted, E 15 embryonic retinas make better grafts for their ability to form consistent laminae and to integrate with host tissue in a fresh lesion paradigm. PMID- 3343108 TI - NMR of skeletal muscle. Differences in relaxation parameters related to extracellular/intracellular fluid spaces. AB - The relationships between the T1 and T2 relaxation times, tissue water content and extracellular fluid space of two types of skeletal muscle groups were studied in rabbits and rats by means of NMR proton spectroscopy (10 MHz). Although there was no significant difference in the total water content between muscles rich in type I (74.5 +/- .8%; soleus) or type II (75.0 +/- .7%; gastrocnemius) fibers, the respective T1 (521 +/- 25 vs. 486 +/- 16 millisecond; p less than .01) and T2 (39.5 +/- 1.8 vs. 36.5 +/- 1.0 millisecond; p less than .01) relaxation times were consistently prolonged. The longer relaxation times of the soleus as compared with the gastrocnemius muscle were related to a larger extracellular fluid space as measured by (35S) sulfate +34.5%; p less than .01). For this reason, it seems likely selective changes in these spaces will be detectable by NMR proton imaging. PMID- 3343109 TI - Functional dynamics of the knee joint by ultrafast, cine-CT. AB - An ultrafast, cine-CT scanner was used to demonstrate the differential mobility of the lateral and medial femoral condyles on their respective tibial plateaus in cadaver knees and to show the kinematic type of motion of the knee joint. Current imaging techniques cannot accomplish this because they do not perform combined quantitative, tomographic, and dynamic studies. Accordingly, this preliminary report presents the data from cine-CT scans of 12 normal intact adult cadaver knees. Scans were obtained at the rate of 14 or 17 per second at 50 or 100 ms exposures through midsagittal planes of the medial and lateral condyles and intercondylar notch. The cine-CT scans were displayed on a CRT and analyzed as closed-loop movies and as isolated images. Each cadaver femoral condyle demonstrated a different combined rolling and gliding motion. Preliminary results on the cadaver knee suggest the lateral femoral condyle moved 2.3 times further on the tibial plateau than its medial counterpart. The percentage of rolling for the lateral condyle was 43%-49%; the percentage of gliding was 51%-57%, with a ratio of rolling to gliding of 1:1.2. The percentage of rolling for the medial condyle was 16%-26%; the percentage of gliding 74%-84% with a ratio of rolling to gliding of 1:3.8. The femoral condyles, tibia, and cruciate ligaments acted as a crossed four-bar linkage in concordance with kinematic theory. The applicability of the cadaver knee results to patient dynamics and diagnosis cannot be determined from this study and awaits further investigations on the in vivo knee. However, ultrafast cine-CT demonstrated the complex knee motion in the cadaver knee joint. PMID- 3343110 TI - Evaluation of the dehydration-rehydration method for production of contrast carrying liposomes. AB - We measured the amounts of three types of radiographic contrast media (RCM) that could be entrapped in liposomes prepared by the dehydration-rehydration vesicle (DRV) technique. To make DRVs, one initially makes water-containing, small unilamellar vesicles, adds contrast media and lyophilizes the mixture. Upon rehydration, the DRVs re-form, passively entrapping RCM. Diatrizoate, iohexol and iotrolan proved to be entrappable in similar amounts (diatrizoate was best), but all of these amounts were less than for other small molecules, such as carboxyfluorescein (P less than 0.05). Entrapment was directly proportional to lipid concentration (r = 0.76; P less than 0.002), and inversely related to iodine concentration (r = 0.86; P less than 0.002). Under ideal conditions with neutral lipids, 19.45 +/- 9.9% of diatrizoate was entrapped, corresponding to 1.05 +/- 0.50 g I per g lipid. These values are close to those achievable for large unilamellar vesicles. Use of an automated mixing device (the Microfluidizer) in place of sonication, facilitated production of large liposome batches and improved entrapment (P less than 0.05). Computed tomography (CT) scans of rats showed 30 and 218 HU of liver and spleen enhancement, respectively, per g I/kg injected DRVs. These studies showed this method (possible augmented by the Microfluidizer) allows efficient production of contrast-carrying liposomes. PMID- 3343112 TI - Breast mass in a farm woman. PMID- 3343111 TI - Iohexol inhibits adenylate cyclase. AB - Previous studies demonstrated that the intravenous administration of the ionic radiographic contrast agent, diatrizoate, and the nonionic agent, iohexol, causes a decrease in the rate of cerebrospinal fluid (CSF) production. Evidence suggests that adrenergic-mediated adenylate cyclase (AC) activity controls CSF production. Diatrizoate was found to inhibit AC activity. The authors now report that iohexol inhibits activity of this enzyme. Adenylate cyclase activity was measured in membrane fractions of bovine choroid plexus in the presence of various concentrations of iohexol. A concentration-dependent inhibition of basal and adrenergic-stimulated AC activity by the contrast agent was observed. The concentration of iohexol that produced a 50% inhibition was about 2.3 mM. This is similar to the concentration of diatrizoate that produced equivalent enzyme inhibition. These results support the contention that one mechanism for the action of contrast media in reducing CSF production involves inhibition of AC activity. PMID- 3343113 TI - Testing as a teaching tool. AB - More than four years ago, the authors initiated testing as a means of obtaining data for evaluating residents. The testing process has evolved now and is used for its teaching value and as a means of objective resident self-evaluation. Testing is designed to provide 10 cases an hour, with characteristics allowing a single diagnosis as a unique answer. No history is provided because a common topic and anatomic area provide a context for each examination. Answers are given during the examination after each question, and discussion follows. All answers are written, and answer sheets are collected. Attendance is high. Test scores are routinely lower than in other forms of evaluation. Testing integrates all aspects of radiology training from cognitive through deductive, simulates written consultations, and provides a means of self-evaluation through rapid feedback. Testing is a viable form of teaching that blends self-evaluation with faculty and peer feedback. PMID- 3343114 TI - The utility of computed tomography in colonic diverticulitis. PMID- 3343115 TI - Radiographic features of appendiceal colic in children. PMID- 3343116 TI - Open the door a little wider for fellowship training. PMID- 3343117 TI - Magnetic resonance imaging of ischemic bowel in rabbit model. AB - Acute mesenteric ischemic bowel disease is a common yet complex disorder with high morbidity and mortality rates predominantly caused by delayed diagnosis. We examined the role of magnetic resonance imaging (MRI) in the early detection of small bowel ischemia using the rabbit model. Surgical ligation of the appropriate arterial vascular supply to the ileum of 10 rabbits produced the ischemic compromise. The animals were imaged at different time intervals after the arterial occlusion. Multislice, T1 and T2-weighted images were obtained in axial and coronal planes. Abnormal findings of the dearterialized segment of bowel were visualized as early as 45 minutes after vascular occlusion. The findings consisted of: (1) bowel wall thickening, (2) two- to three-fold increase in signal intensity from bowel on T2-weighted images, and (3) isointensity or slightly increased signal intensity within the bowel wall on T1-weighted images. MRI appears to be a sensitive, noninvasive technique for the early detection of bowel ischemia in the rabbit animal model. PMID- 3343119 TI - Headache in Parkinson's disease. PMID- 3343118 TI - Acute inflammation of the temporomandibular joint presenting as classical trigeminal neuralgia--case report and hypothesis. PMID- 3343121 TI - Cluster headache-like syndrome due to arteriovenous malformation. PMID- 3343120 TI - Significance of EMG surface electrode placement models and headache findings. PMID- 3343122 TI - The differential effects of biofeedback in the treatment of classical and common migraine. PMID- 3343123 TI - Intravenous aspirin for intractable headache and facial pain. PMID- 3343124 TI - The dexamethasone suppression test in essential headache. PMID- 3343125 TI - The Pain Behavior Questionnaire (PBQ): a global report of pain behavior in chronic headache. PMID- 3343126 TI - Increased platelet glycoprotein IIb reflects an abnormality of the platelet membrane in migraine. PMID- 3343127 TI - Does analgesic abuse cause headaches de novo? PMID- 3343128 TI - Aspartame and headache. PMID- 3343129 TI - Causes of financial difficulty in Catholic hospitals. AB - A study was conducted to see which attributes contribute most to financial distress in Catholic hospitals. The 1982 total population of U.S. Catholic hospitals was examined. The reason for financial distress was found to be more related to management attributes than to financial variables. PMID- 3343131 TI - A still changing health care system. PMID- 3343130 TI - Are international patients the answer to American hospitals' problems? AB - American hospitals hoping to capitalize on the lucrative market for international patients may be in for some surprises. Not only is this market limited, but also the drawbacks may outweigh the potential benefits for hospitals seeking to enter this business. PMID- 3343132 TI - The new hospital challenge: organizing and managing physician organizations. AB - A new challenge facing hospital management is the task of developing a close working relationship with physicians organized to effectively support managed care. How this challenge is met may play a pivotal role in the hospital's future. PMID- 3343133 TI - High-performing managers. PMID- 3343134 TI - Women health care managers: an economic update. AB - In 1980, a survey of women health care managers was performed that documented their career status at that time. This article reports the results of a follow-up survey, done five years later, demonstrating gains in salary and responsibility. PMID- 3343135 TI - HCMR interview: James J. Mongan. Interview by Montague Brown. PMID- 3343136 TI - Wellness days. PMID- 3343137 TI - A hospital wellness program: where challenge meets opportunity. PMID- 3343138 TI - Computerized health risk assessment at the work site. PMID- 3343139 TI - Oncology alert for the home care nurse: hypercalcemia. PMID- 3343140 TI - Nurse/social worker home care. PMID- 3343142 TI - Home care prophecies and predictions, Part II. PMID- 3343141 TI - Documentation in home care: skilled observation. PMID- 3343143 TI - The ability of family practice residents to diagnose depression in outpatients. PMID- 3343145 TI - Physician participation needed in AIDS education. PMID- 3343144 TI - The McDaniel family: the impact of small-group clinical teaching early in the medical school curriculum. PMID- 3343146 TI - AIDS: a challenge for osteopathic physicians. PMID- 3343147 TI - Segmental definition: Part I. A focal point for diagnosis of somatic dysfunction. PMID- 3343148 TI - Postoperative abdominopelvic radiation therapy for ovarian cancer. AB - From 1963 through 1984, 74 patients with Stage I, II, or III epithelial ovarian cancer who completed a total hysterectomy and debulking procedure and had less than 2 cm residual disease were treated with whole abdominal and pelvic boost radiation therapy (WAP) at Yale-New Haven Hospital. WAP consisted of a whole abdominal dose of 1750 to 2500 cGy (at 100-160 cGy per fraction) and a total pelvic dose of 4000-4600 cGy. Based on stage, amount of residual disease, pathologic type, and grade of tumor, the 74 patients were classified into a favorable group (FG) and an unfavorable group (UG) using the classification scheme developed at the Princess Margaret Hospital (PMH). The actuarial survival at 10 years for the FG patients was 77% (+/- 10%, 95% confidence limits) and for the UG patients was only 7% (+/- 13%). Local control of disease in the abdomen and pelvis was 87% in the FG and only 36% in the UG. Severe long-term complications occurred in 7% of the patients and consisted of small bowel obstruction. Our results strongly indicate that the PMH classification of FG and UG is useful in our patient population in determining which subgroup of patients should be offered WAP. PMID- 3343149 TI - Radiotherapy in the treatment of ovarian dysgerminomas. AB - Between 1969 and 1983 a total of 14 patients with ovarian dysgerminoma were treated at the Institute of Oncology and Radiotherapy, the Prince of Wales Hospital, Randwick. The case records of these patients have been reviewed for presenting symptoms, treatment given, and survival following treatment. Excluded from analysis are patients with mixed ovarian germ cell tumors (dysgerminoma and teratoma). Data includes three patients referred with recurrent or residual tumor after primary surgery. Ten patients remain alive (72%). All four patients who died had recurrent intra-abdominal tumor, with or without distant metastases at the time of death. Median duration of follow-up of living patients was 54 months. Survival of those dead ranged from 8 to 168 months following treatment. The place of radiotherapy in treatment is discussed. PMID- 3343150 TI - Adjunctive radiotherapy with strontium-90 in the treatment of conjunctival squamous cell carcinoma. AB - Squamous cell carcinoma of the ocular conjunctiva is a relatively rare malignancy which is attended by a high rate of local recurrence following simple surgical excision. To date, the management of conjunctival squamous cell cancer has been controversial. From 1950 to 1985, 146 consecutive patients with superficial conjunctival squamous cell cancer were treated at the Queensland Radium Institute. All patients were treated by simple surgical excision of the visible conjunctival lesion followed by adjunctive radiotherapy. Of 140 patients with histologically confirmed squamous cell cancer, 123 were treated with a strontium 90 source, 10 with a radon "ring," and 7 with superficial X ray therapy. Standard policy since 1960 has been to deliver an incident dose of 30 Gy in a single fraction within the first 48 post-operative hours to the surgical bed using a strontium-90 source on a stand-off eye applicator. This report will largely focus on the 123 patients who were treated with a strontium-90 source, of whom 107 received 30 Gy, 14 received 40 Gy (pre 1960) and one patient each received 20 and 25 Gy incident dose. Of 131 evaluable patients, there were only 3 who developed local recurrence. All 3 local recurrences developed in elderly men who had presented with extensive superficial primary tumors. Two of the three recurrences occurred in the two patients who were treated with doses less than 30 Gy. Both early and late radiation-induced complications following ablative surgery and treatment with strontium-90 were very uncommon. Three patients developed unsightly conjunctival telangiectasia, 2 patients developed a persistent scleral ulcer and 2 patients developed clinically significant cataracts. This negligible degree of treatment-related side effects contrasts with the experience of 10 patients who had previously been treated with a radon ring, 8 of whom developed serious complications, although none developed local recurrence. On the basis of our excellent local control rates with minimal morbidity we would continue to advocate the use of simple surgical excision followed by 30 Gy beta radiation from a strontium-90 source as the definitive treatment for superficial conjunctival squamous cell cancer. PMID- 3343151 TI - Adjuvant postoperative radiation therapy following radical hysterectomy in stage IB CA of the cervix--analysis of treatment failure. AB - Among 240 patients treated by radiation therapy for clinical Stage IB cancer of the cervix between 1969 and 1980, 38 patients received postoperative pelvic radiation therapy after radical hysterectomy because of positive pelvic lymph nodes and/or close surgical margins. The overall recurrence was 45% (17 of 38), and the major complication rate was 15% in minimum 5-year follow-up. In patients with positive pelvic lymph nodes, the pelvic recurrence was 13% (3 of 23). However, distant metastases alone was 26% (6 of 23), which was the most common treatment failure. In 11 patients with close surgical margins, eight patients had paracervical margins and three had vaginal margins. All five patients with paracervical margins treated with vaginal ovoid irradiation only had pelvic recurrence. No local failure occurred in the other three patients treated with whole pelvic irradiation. All patients with vaginal margin alone treated with vaginal ovoid or whole pelvic irradiation had no recurrence of cancer in the pelvis. On the basis of our data, whole pelvic irradiation with or without vaginal ovoid irradiation is necessary in those with a close paracervical margin. In patients with close vaginal margin, whole pelvic irradiation with or without vaginal ovoid irradiation is recommended. The vaginal ovoid irradiation alone should be limited to very selected cases. PMID- 3343152 TI - The effect of fraction size on control of early glottic cancer. AB - A retrospective analysis of 600 patients treated for head and neck malignancy at the Cooper Hospital/University Medical Center was undertaken. Patients who had surgical intervention (excluding biopsy) were withdrawn from this review. Fifty eight patients with Stage I Glottic Laryngeal Carcinoma were identified and constitute the basis of this report. Various parameters were analyzed to assess their impact on local control. These include age, sex, serum hemoglobin, tumor bulk, differentiation, field size, total dose, total treatment time, and fraction size. Overall local control was 87% with a median follow-up of 63 months. The only factor that influenced local control was fraction size. Of 28 patients treated with 180 cGy fractions, seven (25%) had a local recurrence within 3 years. Twenty-eight patients treated with 200 cGy or greater fractions have had no failures to date. The difference in control rate when comparing the two treatment schema was significant (p less than 0.01). The median dose in the controlled 180 cGy group was 6660 cGy (range, 6300-7020 cGy). In the patients who failed in the 180 cGy group the median dose was 6660 cGy (range, 6480-6840 cGy). The patients receiving 200 cGy fractions or greater had a median dose of 6600 cGy (range, 6000-6950 cGy) and an average dose of 6507 cGy. The mean NSD in the 180 cGy group failing was 1787 RET (range, 1735-1843 RET). Patients who were controlled and received 180 cGy fractions had a median NSD of 1796 RET (range, 1743-1868). The mean NSD in the 200 cGy group was 1847 RET. The median TDF in the 180 cGy group of patients controlled was 102. Those failing also had a TDF of 102 (range, 101-105). Patients receiving 200 cGy fractions or greater had a median TDF of 109. It appears from this data that fraction size is a highly significant factor in our ability to control glottic laryngeal cancer. PMID- 3343153 TI - Nasopharyngeal carcinoma: result of treatment with cis-diamminedichloroplatinum II, 5 fluorouracil, and radiation therapy. AB - Combined CT (CDDP + 5FU) and RT were given to 28 patients with NPC during July 1982-May 1985. Two, 1, 4, and 21 were in Stages I-IV (AJC), respectively. None had distant metastasis. Four did not complete the planned treatment, and one each had more or fewer CT courses than planned. The median duration of follow-up of surviving patients was 29 months (19-52,x 31.1). Objective response (CR + PR) at the primary lesion was 27/28 (96.4%), whereas CR was 23/28 (82%). CR + PR and CR of the regional nodes were 21/22 (95.5%) and 18/22 (82%) respectively. Remaining node in the 2 patients, who did not prematurely die were pathologically negative. Response at N site should therefore be 100% CR. Only patients with T3 (1/5) and T4 (3/13) lesions had residual disease at the T site after initial treatment. Salvage therapy was able to induce CR in all asymptomatic PR patients. There were 4 relapses, 2 at T, and 1 each at T + N and T + M sites. All M disease occurred in patients with huge and/or low cervical lymphadenopathy. Five patients died, one of an unrelated disease, and one each of T, M, T + N, and T + M diseases. The remaining 23 patients were still alive, and all except 3 were free of disease. Side effects, mainly from RT, were clinically acceptable. One had transient cervical myelitis. Myelosuppression was mild and of short duration. Activity of CT was seen at both T, and N sites after the upfront CT. Compared to our previous experience using RT alone, the result of this study suggested a positive role of CT in this disease. However, future prospective randomized trials are required to better define its role. PMID- 3343154 TI - The use of postoperative irradiation for the prevention of heterotopic bone formation after total hip replacement. AB - Formation of heterotopic bone (HTB) following total hip replacement may partially or completely ankylose the joint space, causing pain and/or limiting the range of motion. Patients at high risk for formation of HTB postoperatively include those with previous HTB formation, heterotopic osteoarthritis, and active rheumatoid spondylitis. Patients in these high risk groups have a 63-69% incidence of post operative HTB formation, usually seen radiographically by 2 months post operation. From 1980-1986 twenty-nine hips in 28 consecutively treated patients were irradiated post-operatively at the UCLA Center for the Health Sciences. The indication for irradiation was documented HTB formation previously in 26 of the 27 hips presented below. From 1980-1982 patients received 20 Gray (Gy) in 2 Gy fractions; from 1982-1986 the dose was reduced to 10 Gy in 2 Gy fractions. Twenty seven hips in 26 patients completed therapy and were available for evaluation, with a minimum of 2 month follow-up, and a median follow-up of 12 months. Three of 27 hips developed significant HTB (Brooker grade III or IV) post-operatively, whereas 5 of 27 hips developed minor, nonsymptomatic HTB (Brooker grade I). When irradiation was begun by postoperative day 4, 0 of 17 hips formed significant HTB. If irradiation began after post-operative day 4, 3 of 10 hips formed significant HTB (Brooker grade III or IV). These 3 hips received doses of 10 Gy in one hip and 20 Gy in the other 2 hips. There were no differences in the incidence or severity of side effects in the 10 Gy vs. the 20 Gy treatment groups. Eighteen hips received 10 Gy, 8 hips 20 Gy and, 1 hip 12 Gy. In conclusion, 10 Gy in 5 fractions appears as effective as 20 Gy in 10 fractions at preventing post-operative formation of HTB. For optimal results, treatment should begin as early as possible prior to post-operative day 4. PMID- 3343155 TI - Three-dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. AB - Conservative surgery combined with radiation therapy for the treatment of early breast carcinoma has been shown to achieve both a high rate of local tumor control and good cosmetic results with a minimum of complications. Whether the internal mammary lymph nodes (IMNs) should be included in the treatment volume is a topic of considerable controversy. Radionuclide internal mammary node lymphoscintigraphy (IMN-LS) can locate these nodes in three dimensions. We have analyzed the results of IMN-LS in 167 patients imaged at the Dana-Farber Cancer Institute and treated at the Joint Center for Radiation Therapy between 1977 and 1980. The location of the IMNs was found variable from patient to patient. At least one IMN was not included within tangential fields arbitrarily arranged to have a medial entrance point 3.0 cm across the midline in 17% of evaluable patients. However, 48% and 66% of patients had IMNs that could be adequately treated with fields positioned only 1.0 cm or 2.0 cm across midline, respectively. We conclude that when treatment of the IMNs is warranted, IMN-LS not only assures their complete coverage in the majority of patients but also may help reduce the amount of heart and lung irradiated. PMID- 3343156 TI - Radiotherapy of the rhabdomyosarcoma R1H of the rat: the influence of the number of fractions on tumor and skin response. AB - The influence of the number of fractions on tumor and skin response to fractionated irradiation was studied. R1H rhabdomyosarcomas of the rat (volume doubling time 3 days) were irradiated with 6, 18, 30, or 42 fractions in 6 weeks. Total doses of 45, 60, or 75 Gy were applied in each fractionation scheme, that is, the dose per fraction ranged from 1.07 to 12.5 Gy. Tumor response was assessed by tumor control probability and tumor net growth delay. A clearcut reduction of skin damage was observed with increasing number of fractions, whereas the tumor response was found to be the same whether the dose was given in 6, 18, 30, or 42 fractions. Thus, the fractionation regimens were more effective than expected from calculations based on single-dose in situ survival curves. This result can be explained by assuming that the clonogenic tumor cells become less hypoxic with increasing number of fractions. Since normal tissue damage decreases with increasing number of fractions, the therapeutic gain may be improved by applying a greater number of fractions. PMID- 3343157 TI - Dose distribution of neutron beam and chromosome analysis. AB - Chromosome analysis using peripheral lymphocytes is a sensitive and reliable indicator of the biological effect of radiation at low radiation doses. In the present study, using this chromosome aberration analysis, we tried to investigate the radiation dose distribution within and around the radiation field of a 6 MeV neutron beam. The efficient induction of dicentrics and rings at the irradiation of neutrons compared to those of gamma or X rays especially in a lower dose range, results in a dominant linear component in the linear quadratic model in the dose response relation of a chromosome aberration formation. A marked increase of RBE (relative biological effectiveness) in a lower dose range of neutrons was demonstrated. The radiation doses of the neutron beam as a function of depth, estimated from the yields of dicentrics and rings in a water phantom revealed a fairly good agreement with doses that were physically obtained. The radiation portal margin of the neutron beam was demonstrated to be not as sharp due to a wide penumbra. This wide penumbra and high RBE value, especially at lower dose range of the neutron beam may contribute to the induction of secondary malignancies in the normal tissue surrounding the tumor mass. PMID- 3343158 TI - Applicator for optimum cobalt-60 primary breast treatments. AB - A breast applicator has been designed to optimize 3 field breast treatments for 60Co. The device has a six half value layer beam splitting block constructed in two sections. The larger permanently mounted section is sufficient for treating 90% of the patients. Slots are available for mounting cerroband blocks, and any of five brass half field wedges. A magnetically attached front and back-pointer assembly readily breaks away in the event of a collision between pointer and patient. With this design the breast applicator with wedges and blocks has in field surface doses reduced to that of an open field without accessory devices. The 50-90% dose decrement of the radiation penumbra for the half field block is comparable to that for the field edge of a typical 6 MV X ray unit, although the 50-10% decrement is larger. The average out-of-field dose at the surface is 8% and is 5% at the depth of dose maximum. The combination for this applicator of sharp penumbra and low out-of-field dose leads to reduced lung and opposite breast doses. The latter was confirmed with TLD measurements on 10 patients, and yielded an average opposite breast dose of 230 cGy for a 4600 cGy prescription. Thus, half-field blocking devices do not preclude, as has been stated in the literature, acceptable opposite breast doses. In addition, proper design of these devices can significantly improve the radiation characteristics for primary breast treatments. PMID- 3343159 TI - Hyperthermic therapy of deep seated tumors: comparison of the heating efficiencies of an annular array applicator and a capacitively coupled radiofrequency system. AB - Among 82 cases of deep seated tumors treated by hyperthermia with an annular array applicator (AA) and/or a capacitively coupled 8 mHz system (CCS) combined with radiation therapy, 13 cases were treated by both devices. The efficiencies of tumor heating were compared in terms of the time required to attain 42 degrees C, the duration of heating time and the thermal dose as determined by a biological iso-effect formula for equivalent minutes at 42.5 degrees C. Temperature profiles and percent of temperature levels greater than 42 degrees C were better in the cases treated by the AA, but higher thermal doses were obtained with the CCS because longer treatment times were tolerated with the CCS than with the AA. Methods are necessary to prevent excess elevation of body temperature in the case of the AA, and to reduce superficial pain where the applicators contact the skin in the case of the CCS. PMID- 3343160 TI - Biochemical and cellular effects of radiofrequency induced interstitial hyperthermia on normal canine liver. AB - Interstitial hyperthermia (44.0 +/- 0.5 degrees C for 40 minutes) was delivered to the livers of 16 dogs to determine acute effects of treatment on blood chemistry, histology, and cellular appearance of normal liver. SGOT in treated animals peaked immediately at 300 +/- 21 U/L (within 2 hrs) and returned to control value within 7 days. LDH levels peaked at 1 day post-treatment and again at 2 weeks (300 +/- 16 U/L and 340 +/- 25 U/L respectively) and returned to pre treatment values by week 4. SGPT remained elevated for 6 to 7 days following hyperthermia, but returned to control value at 2 weeks. There was also a rise in alkaline phosphatase (200 +/- 14 U/L 1 day post-treatment), which returned to a pre-treatment level by week 3. Changes in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, and alkaline phosphatase were attributed to both liver parenchymal damage induced by hyperthermia and to surgery. Other deviations in the blood chemistries and hematological parameters measured were ascribed to the stress response from surgical intervention, or to the resultant hemodilution from fluids during surgery. Microscopic examination upon necropsy, performed 4 weeks post operatively, displayed limited fibrosis with some alteration of liver architecture, generalized sinusoidal dilation and red blood cells in the space of Disse. Cellular ultrastructure changes showed an increase of myelin figures, but mitochondria and other cellular organelles remained essentially normal. Localized tissue inflammation and some loss of function occurred in response to localized hyperthermia for this volume of tissue at therapeutic temperatures. This study showed that the technique was feasible and confirmed that the parenchymal damage caused by interstitial hyperthermia did not produce the severe loss of function that might have been expected. PMID- 3343161 TI - The distribution of power and heat produced by interstitial microwave antenna arrays: II. The role of antenna spacing and insertion depth. AB - The distribution of power and temperature generated by 915 MHz interstitial microwave antenna arrays was studied in static muscle-equivalent phantoms and both perfused and non-perfused canine thigh muscle. These arrays, which would form the geometric basis of larger volume implants, consisted of four parallel antennas oriented such that transverse to their long axes they formed the corners of a square. Arrays with 2 and 3 cm sides were compared at various depths of insertion where the nodes for all four antennas were coincident at the same depth. The position relative to the antenna nodes of the maximum power and highest temperature within the array volume varied with the depth of insertion of the antennas. Though power dropped rapidly distal to the nodes at all depths, a shift in the location of the maximum power proximal to the nodes resulted in an increase in the effective heating volume at certain insertion depths. For 2 cm array spacing the highest power and temperature were measured along the central axis of the array at all insertion depths. However, arrays using 3 cm spacing generated their maximum power adjacent to the antennas with only 50% of this level occurring along the central axis. When the temperature produced by 3 cm arrays was measured in phantoms midway through simulated 30-minute hyperthermia treatments, the effect of thermal conduction on the temperature distribution was evident. Though power was only 50% centrally, the highest temperatures occurred there. This same pattern of central heating occurred in perfused canine muscle demonstrating the importance of conductive and convective heat redistribution in reducing thermal gradients within the array volume. PMID- 3343162 TI - The structure of radiation oncology practices in the continental United States. AB - The American College of Radiology periodically collects data on radiation oncology facilities with megavoltage equipment. The results of the 1986 survey are summarized, with specific reference to the substantial growth in free standing facilities. PMID- 3343163 TI - A unified approach to dose-effect relationships in radiotherapy. I: Modified TDF and linear quadratic equations. AB - A linear quadratic factor analogue (LQF) to the variable-exponent TDF model is introduced. In both of these models, account is taken of the volume of tissue irradiated. Scaling factors are used such that an LQF or a TDF of 100 represents tolerance for each volume or partial volume of each tissue or organ irradiated. These models are sufficient for tissues which are irradiated fairly homogeneously. Examples illustrate the use of these models. PMID- 3343164 TI - A unified approach to dose-effect relationships in radiotherapy. II: Inhomogeneous dose distributions. AB - Conventional dose-effect relationships, such as those based upon the NSD or linear-quadratic concepts, do not account for dose inhomogeneities. Only a single "dose" value can be used in these equations and this can give rise to significant errors in the estimation of the "tolerance" dose in situations where dose distributions are inhomogeneous. This paper presents a method of "integrating" the biologically effective dose over the entire volume of each organ or tissue irradiated. Integral forms of the variable-exponent TDF and linear quadratic factor (LQF) models (ITDF and ILQF, respectively) can be used to determine whether or not any organ or tissue in an irradiated volume has exceeded tolerance, regardless of dose distribution non-uniformity. Several examples are given with comparisons to solutions obtained by conventional dose-effect models. PMID- 3343166 TI - Does parasternal irradiation reduce thoracic vertebral metastases in breast cancer? AB - A review of 197 patients with bone metastases from breast carcinoma was undertaken to assess the effect of adjuvant parasternal irradiation on the distribution of those metastases. A total of 128 patients (Group I) received radiation. The control group consisted of 69 patients (Group II) who did not receive adjuvant radiation. The dose absorbed by the mid-thoracic vertebrae (T3 to T8) varied from 10 Gy in 3 weeks to 20 Gy in 4 weeks. The distribution of bone metastases was analyzed at the initial development in the 197 patients. Repeat assessments (X ray/scans) were available for analysis in 132 patients. Patients in Group I had less metastases from T3 to T8: 37/128 (29%), vs 30/69 (43.5%) for patients in Group II: (chi 2 = 3.62; p less than 0.10). For the 132 patients with serial assessments, the difference at last evaluation was more significant: 45/86 (52%) in Group I, vs 36/46 (78%) in Group II: (chi 2 = 7.44; p less than 0.01). The data shows that patients receiving low-dose exit beam irradiation from the parasternal field have fewer mid-thoracic bone metastases. Potential implications are discussed. PMID- 3343165 TI - Second primary cancers of the head and neck following treatment of initial primary head and neck cancers. AB - The risk of a second primary cancer arising in the head and neck, following surgical or radiation treatment of an initial primary cancer in the head and neck, was evaluated for 2,151 patients whose first cancers were diagnosed and treated at UCLA between 1955 and 1979. Based on follow-up data ranging from 5 to 30 years, the rate of development of second cancers of the head and neck was in excess of 2.5 per 1000 person-years at risk. There was no statistically significant difference in the frequency or post-treatment interval of second primary cancers related to the type of treatment of the first cancer, whether that was surgery, radiation therapy, or surgery plus radiation therapy. PMID- 3343167 TI - Remote interstitial afterloading in cancer of the prostate: preliminary experience with the MicroSelectron. AB - Brachytherapy in the treatment of prostate cancer is an accepted modality. A considerable experience has been accrued using Iridium interstitial therapy. The major problem associated with this choice is that of radioprotection. We describe the first clinical use of the MicroSelectron, a remote afterloading device, in prostate brachytherapy. Twenty-six patients have now been treated using this system. Approximately 55 treatment interruptions with an average 5 hr increase in overall treatment time occurs. The initial problems associated with instituting remote afterloading to prostate brachytherapy and their solutions are discussed. PMID- 3343168 TI - Hypofractionated external radiation with high and low dose rates in the treatment of advanced cancer of the cervix. AB - Thirteen patients with cancer of the cervix Stage IIIb (heavy) were treated with high (9) and low (4) dose rates, once a week. A total dose of 4200 cGy was delivered over 7 weeks with a fraction size of 600 cGy. Six of nine patients showed complete response following high dose rate hypofractionated radiation. It is felt that synchronization of cells into a sensitive phase during low dose rate radiation is not the determinant of outcome even when duration of treatment is only 5 to 6 hours. PMID- 3343169 TI - On the choice of phantom material for the dosimetry of 192Ir sources. AB - Dosimetric characteristics of polystyrene, solid water, and polymethylmethacrylate were examined and compared to water to determine the suitability of these solid materials for the dosimetry of 192Ir. Ionization charge measured in each of the four media as a function of depth and depth-dose curves calculated by Monte Carlo simulation show that the three solids are equivalent to each other and to water under full scattering conditions. Photon energy spectra generated from the Monte Carlo simulation show little variation for the different media. Mass energy absorption coefficients and exposure-to-dose conversion factors were calculated as a function of depth for these spectra. Measured tissue attenuation factors are in excellent agreement with Meisberger's "selected" values. The radial dose function, which describes the change in dose with distance in phantom exclusive of the inverse square law, was calculated from the tissue attenuation factor and found to be in significant disagreement with Dale's Monte Carlo values. The reason for this discrepancy is discussed. PMID- 3343170 TI - Dose prescription dilemma. PMID- 3343171 TI - Accurate English. PMID- 3343172 TI - Interstitial implantation is essential. PMID- 3343173 TI - SVC syndrome and thrombus formation. PMID- 3343175 TI - Toxocaral larva migrans. PMID- 3343174 TI - The duty to give expert testimony. PMID- 3343176 TI - Critical of Brucellosis Eradication Program. PMID- 3343177 TI - Serial determination of thyroxine concentrations in hyperthyroid cats. AB - Serum thyroxine (T4) concentrations of 10 hyperthyroid cats were measured at hourly intervals between 9 AM and 4 PM. In 5 cats, blood samples were obtained by jugular venipuncture; the remaining 5 cats had blood samples obtained from jugular catheters. Over the 7-hour period, a significant temporal (diurnal) variation was not identified in the serum T4 concentrations of the cats (P greater than 0.01). The lowest mean serum T4 concentration (9.1 micrograms/dl) was measured at 3 PM and was 14.2% less than the highest mean serum T4 concentration (10.6 micrograms/dl) measured at 9 AM. Though there were fluctuations in serum T4 concentrations during the 7-hour period, the differences were not systematic. The maximal variation in serum T4 concentrations over the 7 hour period averaged less than 21%. Despite the random variations during the 7 hour period, none of the measured serum T4 concentrations was in the normal range. Measurement of serum T4 concentration from randomly obtained blood samples was determined to be reliable for diagnosing feline hyperthyroidism. PMID- 3343178 TI - Treatment of cancer. PMID- 3343179 TI - Use of 2,3,2-tetramine as a hepatic copper chelating agent for treatment of copper hepatotoxicosis in Bedlington terriers. AB - Five Bedlington Terriers with inherited copper (Cu) hepatotoxicosis and with hepatic Cu concentrations ranging from 3,000 to 11,000 micrograms/g of dry weight (normal, less than 350 micrograms/g of dry weight) were treated daily for up to 200 days with 2,3,2-tetramine tetrahydrochloride. During treatment, no change was made in the dietary Cu intake, which ranged from 12 to 16 micrograms/g of dry diet. Concentrations of hepatic and serum Cu, iron, and zinc were determined before and at the conclusion of the treatment period. In one dog, 24-hour urinary Cu concentration was measured before and during treatment. A liver biopsy specimen obtained after treatment had significantly (P less than 0.05) reduced hepatic Cu concentration (3,282 micrograms/g of dry weight; a 54.9% reduction), compared with the pretreatment value (7,281 micrograms/g of dry weight). After treatment, there was an overall general lessening of the extent of hepatic morphologic damage. Cytochemical examination for Cu in rhodanine-stained biopsy specimens revealed decreased numbers of Cu-laden hepatic lysosomes. The mean daily urinary Cu concentration increased as much as 25-fold during 2,3,2 tetramine treatment. Hepatic iron and zinc concentrations and serum Cu concentrations remained within normal ranges after treatment. Clinical or laboratory evidence of 2,3,2-tetramine toxicosis was not detected during treatment. These findings indicated that in affected Bedlington Terriers, 2,3,2 tetramine was a safe and rapid chelating agent of hepatic Cu. PMID- 3343180 TI - Gentamicin pharmacokinetics and nephrotoxicity in naturally acquired and experimentally induced disease in dogs. AB - Pharmacokinetic disposition of gentamicin was studied in 69 dogs--12 control and 33 subtotally nephrectomized dogs representing combined data from previous experimental studies, and 24 dogs with a variety of diseases and degrees of renal dysfunction. Drug disposition varied considerably within and between diseases, and dosages had to be altered to achieve therapeutic drug concentrations and to minimize drug toxicosis. Decreased drug clearance when serum creatinine and urea nitrogen concentrations are normal may be indicative of subclinical renal disease and therefore may indicate a predisposition for development of nephrotoxicosis. Results of the study indicated the need to individualize aminoglycoside dosage regimens on the basis of pharmacokinetic disposition of drug, especially in dogs with preexisting subclinical renal dysfunction. Because of the large variability normally encountered in dogs with various diseases, monitoring of renal function alone is not sufficient to accurately predict gentamicin clearance, volume of distribution, or half-life. PMID- 3343181 TI - A veterinarian's involvement in the field of human-animal relationships. PMID- 3343182 TI - Survival of a dog with pneumonia caused by Mycobacterium fortuitum. AB - Pneumonia caused by Mycobacterium fortuitum was diagnosed in the left lung lobes of a 3-year-old male Samoyed. Unilateral pneumonectomy and antibiotic treatment (primarily amoxicillin trihydrate-clavulanate potassium and kanamycin) were associated with resolution of the pneumonia. In dogs, M fortuitum causes pulmonary disease that radiographically resembles bacterial pneumonia. Therefore, M fortuitum infection should be considered in dogs with radiographic signs of bronchopneumonia that worsen despite antibiotic treatment. PMID- 3343184 TI - Assessing degree of hyperthyroidism in cats. PMID- 3343183 TI - Eumycotic mycetoma caused by Pseudallescheria boydii in the abdominal cavity of a dog. AB - An abdominal eumycotic mycetoma with multiorgan dissemination was diagnosed in a 2-year-old dog. Clinical signs included fever, vomiting, diarrhea, weight loss, and a palpable abdominal mass. The dog developed disseminated intravascular coagulation and died. Pseudallescheria boydii was isolated from the abdominal mass, liver, and peritoneal fluid. Relevant history included an ovariohysterectomy when the dog was 6 months old, which was complicated by dehiscence of the incision site and evisceration. It appears that P boydii has a propensity for establishing itself in the abdominal cavity of the dog, subsequent to surgical dehiscence. PMID- 3343185 TI - Seizures as a manifestation of primary hyperparathyroidism in a dog. AB - Hypercalcemia caused by primary hyperparathyroidism was believed to be responsible for seizures in a dog. A diagnostic evaluation showed no primary causes of seizures. After surgical excision of the adenomatous parathyroid gland, phenobarbital treatment was discontinued, without recurrence of seizures. PMID- 3343186 TI - Ophthalmic corticosteroid therapy: systemic effects in the dog. AB - Degenerative myopathy suggestive of glucocorticoid-induced myopathy was diagnosed in a 10-year-old female Poodle X Pekingese dog with a history of progressive lameness. Electromyography revealed bizarre high-frequency discharges. Evidence of adrenal suppression was obtained in response to exogenous ACTH. The predominant source of corticosteroid was an ophthalmic preparation used in the management of keratoconjunctivitis sicca. Considering the apparent adverse effects of the corticosteroid in this case, a study was undertaken to determine the systemic effects, if any, induced by long-term ophthalmic administration of 0.1% dexamethasone suspension in healthy adult dogs. Dogs in one group (n = 5) were treated 4 times daily for 8 weeks, and dogs in another group (n = 5) were treated 4 times daily for 16 weeks. All dogs remained healthy throughout the study, but dexamethasone-treated dogs developed marked adrenal suppression, beginning the second week of treatment and intensifying throughout the treatment period. Histopathologic changes in the liver of dexamethasone-treated dogs included scattered foci of vacuolated hepatocytes, increased hepatocytic glycogen content, and ballooning degeneration of hepatocytes. Muscle specimens were histologically, histochemically, and electromyographically normal. PMID- 3343187 TI - Cerebral coenurosis in a cat. AB - Coenurus serialis, the intermediate stage of Taenia serialis, was the cause of progressive, fatal, intracranial disease in a 5-year-old cat. X-Ray computed tomographic findings were identical to those associated with intracranial parasitic cysts in people, in whom x-ray computed tomographic features are considered pathognomonic and superior to those of other diagnostic methods. The presumed source of the coenurus was the owner's dog. PMID- 3343189 TI - Intraocular melanoma with multiple metastases in a cat. AB - An 11-year-old cat with an intraocular melanoma was treated for 2 years for the secondary effects of the tumor (glaucoma, exposure keratitis) before enucleation was required. One year after enucleation, the cat was examined because of labored breathing. The cat was thin, appeared depressed, and had signs of respiratory compromise secondary to pleural effusion. Treatment was not instituted, and the cat was euthanatized. Metastasis of the primary melanoma to the lungs, pericardium, parietal pleura, mediastinum, hilar lymph nodes, diaphragm, liver, and omentum was confirmed at necropsy. Intraocular melanomas in the cat have been implicated to have a greater malignant potential than those in the dog; however, few cases have been reported with long-term follow-up information. PMID- 3343188 TI - Methemoglobinemia associated with dermal application of benzocaine cream in a cat. AB - Benzocaine, an ester-type local anesthetic, was believed responsible for apparent methemoglobinemia in a cat. The cat was admitted with acute respiratory distress, vomiting, and collapse, which began 15 to 20 minutes after topical application of the drug. Treatment consisted of supportive therapy and intravenous administration of methylene blue. The respiratory rate improved within 5 to 10 minutes of methylene blue administration and continued over a period of 2 hours. Benzocaine-induced methemoglobinemia has been reported in man, dogs, and cats. This report supports the findings of others regarding the potential toxicity of topical ester-type local anesthetics. PMID- 3343190 TI - Canine hemangiopericytoma: 23 cases (1967-1984). AB - The medical records of 23 histopathologically confirmed cases of canine hemangiopericytoma were reviewed. Ninety-one percent (21/23) of the dogs were 7 years old or older, and 70% (16/23) were female. Seventy-four percent (20/27) of the tumors developed on the extremities. Recurrence rates were 31% (5/16) with surgical excision only, and 60% (3/5) with surgical excision combined with radiotherapy. Tumor recurrence did not appear to be related to mitotic index. Metastasis was suspected in one of the dogs, but was not confirmed. PMID- 3343191 TI - Second meiotic nondisjunction is not increased in postovulatory aged murine oocytes fertilized in vitro. AB - We used an in vitro fertilization system to examine the effects of postovulatory oocyte age on nondisjunction at the second meiotic division. After ovulatory inducing injections of hormone, we recovered mouse oocytes either at the estimated time of ovulation (controls) or 2, 4, 5, 10, or 14 h later. Oocytes were subjected to an in vitro fertilization procedure, and chromosomal preparations were made from first cleavage metaphase eggs. The first cleavage assay reveals morphologically distinguishable paternal and maternal chromosomes. Many of the aged oocytes were activated rather than fertilized by the in vitro procedure, but could still be analyzed for nondisjunction. We found a tendency toward retention of the second polar body after 10 and 14 h aging. A total of 488 maternal genomes, 290 of which were in the control group, were analyzable for nondisjunction. Seven hyperhaploid genomes (2.4%) were observed in the controls and 6 (3.0%) in the combined aged group. The difference between these two frequencies is not significant (Gadj = 0.164, P greater than 0.50). In the aged group, one hyperhaploid genome was in the 2-h population, three in the 5-h population, and two in the 10-h population. We were unable to find any significant increase in the frequency of nondisjunction after postovulatory oocyte aging. PMID- 3343193 TI - Psychiatric disorder and juvenile delinquency in adopted children and adolescents. PMID- 3343194 TI - Affective and psychotic psychopathology in hospitalized adolescents. PMID- 3343192 TI - Microtiter micromass cultures of limb-bud mesenchymal cells. AB - A method is described for growing high-density micromass cultures of chick and mouse limb mesenchyme cells in 96-well microtiter plates (microT microM cultures). Rapid quantitative estimates of chondrogenic expression were obtained by automated spectrophotometric analysis of Alcian-blue-stained cartilage matrix extracts performed in the wells in which the cells had been grown. Quantitative estimates of myogenic expression were obtained similarly using anti-sarcomere myosin monoclonal antibody and modified ELISA techniques. This microT microM ELISA method may be adapted for use with other antigens for which specific antibodies are available. These methods were used to compare cartilage and muscle differentiation in 1 to 4 d microT microM cultures grown in serum-containing (SCM) and defined (DM) media. The DM contains minimal additives (insulin, hydrocortisone, and in some cases, ascorbate or transferrin) and supports both chondrogenesis and myogenesis. The colorimetric analyses agree well with the morphologic appraisal of chondrogenesis and myogenesis. Similar numbers of cartilage nodules formed in all cultures, but in DM the nodules failed to enlarge; explaining the reduced matrix synthesis in DM as compared with SCM, and suggesting that nodule enlargement is a discrete, serum-dependent step. Studies of selected additives to DM show that transferrin enhances myogenesis, ascorbic acid enhances chondrogenesis, and retinoic acid inhibits chondrogenesis. Together, the microT microM system, in situ colorimetric assays of chondrogenesis and myogenesis, and DM will allow rapid prescreening of teratogens and screening of various bioactive compounds (e.g., hormones, growth factors, vitamins, adhesion factors) for effects on limb mesenchymal cell differentiation. PMID- 3343195 TI - Phenomenology of depression in children and adolescents. PMID- 3343197 TI - Daily ratings on a child psychiatric unit: psychometric evaluation of the child behavior rating form. PMID- 3343196 TI - Diagnoses, catecholamine metabolism, and plasma dopamine-beta-hydroxylase. PMID- 3343199 TI - In memoriam--DSM-III. PMID- 3343198 TI - Bipolar disorder in a six-year-old boy: a diagnosis by proxy. PMID- 3343200 TI - Treatment compliance in ADD. PMID- 3343201 TI - More on Munchausen by proxy. PMID- 3343202 TI - Tinnitus and hallucinations. PMID- 3343203 TI - Drug-induced hallucinations. PMID- 3343204 TI - Normal children at risk for suicidal behavior: a two-year follow-up study. PMID- 3343205 TI - Perception of family conflict resolution and depressive symptomatology in adolescents. PMID- 3343206 TI - Recurrent depression in adolescents: a follow-up study. PMID- 3343207 TI - Generalized hyperkinesis: follow-up study from age 7 to 13 years. PMID- 3343208 TI - Attention deficit disorder and methylphenidate: a multilevel analysis of dose response effects on children's impulsivity across settings. PMID- 3343209 TI - Effects of methylphenidate dosage in hyperactive reading-disabled children: I. Behavior and cognitive performance effects. PMID- 3343210 TI - Effects of methylphenidate dosage in hyperactive reading-disabled children: II. Reading achievement. PMID- 3343211 TI - The future of child and adolescent psychiatry: if not now, when? PMID- 3343212 TI - Methylphenidate-induced delusional disorder in a child with attention deficit disorder with hyperactivity. PMID- 3343214 TI - What happens to early memories of trauma? A study of twenty children under age five at the time of documented traumatic events. PMID- 3343213 TI - Investigating psychopathological consequences of a disaster in children: a pilot study incorporating a structured diagnostic interview. PMID- 3343215 TI - Turgor pressure responses of a gram-negative bacterium to antibiotic treatment, measured by collapse of gas vesicles. AB - The internal hydrostatic pressure of Ancylobacter aquaticus was measured by collapsing the gas vesicles with an externally applied pressure. Turgor pressure was measured in conjunction with various antibiotic treatments to elucidate some aspects of the biophysics of gram-negative cell wall function. Differences in the effects of these drugs either alone or in combination with other treatments were related to known biochemical activities of these drugs. Our previous work, demonstrating a heterogeneous cellular response to beta-lactam antibodies, was confirmed and extended. Most of the cell wall growth-inhibiting antibiotics resulted in some cells (those in component I) developing a higher pressure, while the remainder (those in component II) lost turgor. Although the fraction of the cells in each component varied a little from subculture to subculture, it did not vary with time or choice of antibiotic treatment. Mecillinam gave a nearly monophasic response. All antibiotics blocking macromolecular synthesis gave monophasic curves. The 50% collapse pressure in some cases, however, was lower higher, or the same as the control. PMID- 3343216 TI - New loci required for Streptomyces coelicolor morphological and physiological differentiation. AB - Streptomyces coelicolor colonies differentiate both morphologically, producing aerial spore chains, and physiologically, producing antibiotics as secondary metabolites. Single mutations, which block both aspects of differentiation, define bld (bald colony) genes. To identify new bld genes, mutagenized colonies were screened for blocks in the earliest stage of sporulation, the formation of aerial mycelia, and blocks in antibiotic synthesis. The mutations in 12 mutants were mapped; in each strain, the pleiotropic phenotype was due to a single mutation. Seven of the strains contained mutations in known bld loci, bldA and bldB. Three strains contained mutations in a new locus, bldG, and two contained mutations in another new locus, bldH. Like the previously defined bldA mutants, the bldG and bldH mutants were developmentally blocked on glucose. On a variety of carbon sources whose utilization was subject to glucose repression, the developmental blocks were partially relieved for bldG (and bldA) mutants and fully relieved for bldH mutants. These results are compatible with an hypothesis which suggests that there are two alternative controls on S. coelicolor differentiation, one of which is glucose repressible. PMID- 3343217 TI - Genomic instability in Rhizobium phaseoli. AB - Experience from different laboratories indicates that Rhizobium strains can generate variability in regard to some phenotypic characteristics such as colony morphology or symbiotic properties. On the other hand, several reports suggest that under certain stress conditions or genetic manipulations Rhizobium cells can present genomic rearrangements. In search of frequent genomic rearrangements, we analyzed three Rhizobium strains under laboratory conditions that are not considered to cause stress in bacterial populations. DNAs from direct descendants of a single cell were analyzed in regard to the hybridization patterns obtained, using as probes different recombinant plasmids or cosmids; while most of the probes utilized did not show differences in the hybridization patterns, some of them revealed the occurrence of frequent genomic rearrangements. The implications and possible biological significance of these observations are discussed. PMID- 3343218 TI - Regulation of the fixA gene and fixBC operon in Bradyrhizobium japonicum. AB - The transcriptional start site of the Bradyrhizobium japonicum fixBC operon was identified by nuclease S1 mapping. It was located approximately 700 base pairs upstream of fixB and was preceded by a promoter sequence that showed strong homology to the B. japonicum fixA promoter and thus to the general nif consensus promoter sequence. Further transcript mapping experiments revealed that fixA and fixBC transcription in B. japonicum strictly depended on the presence of the regulatory gene nifA and on low oxygen partial pressure. Consistent with these data, chromosomally integrated fixA- and fixB-lacZ fusions expressed beta galactosidase activity only in the wild type but not in a nifA mutant and only under microaerobic but not aerobic growth conditions. The presence of nifA accounted for a 19-fold and 44-fold activation of the fixA and fixB promoters, respectively. These results show that the fixA and fixBC genes are regulated in a way similar to that of the nitrogenase genes nifH and nifDK. A very peculiar finding was that the fixA and fixB promoters, when they were located on plasmids, could hardly be activated by the NifA protein, irrespective of whether this was tested in Escherichia coli or B. japonicum backgrounds. This is in clear contrast to the situation with nifH and nifD promoters. PMID- 3343219 TI - A heat shock operon in Coxiella burnetti produces a major antigen homologous to a protein in both mycobacteria and Escherichia coli. AB - A gene library from the DNA of Coxiella burnetii has been constructed in the cosmid vector pHC79. A particular clone, pJB196, reacted strongly with Coxiella specific antibodies elicited in a number of different species of animals. This clone produced two abundant C. burnetii-specific polypeptides, a 14-kilodalton nonimmunoreactive protein and a 62-kilodalton immunoreactive protein. Sequencing identified two open reading frames, encoding polypeptides of 10.5 and 58.3 kilodaltons. The only transcriptional control element observed on the 5' side of the initiation codon resembled a heat shock promoter. This heat shock promoter was functionally regulated in Escherichia coli, since both proteins were produced by growth conditions at 37 degrees C and neither protein was detected at 23 degrees C. There were four sequences from the literature that were highly homologous (greater than 50%) to the 62-kilodalton protein from C. burnetii. Three were from Mycobacterium species and represent the immunodominant antigen of this genus. The other was from E. coli, detected as a gene that complements or suppresses a temperature-sensitive RNase activity. Since the recombinant protein was immunogenic, it may serve as an efficacious vaccine against C. burnetii and other pathogenic microorganisms that express the conserved antigen. PMID- 3343220 TI - Mobilization of Bacteroides plasmids by Bacteroides conjugal elements. AB - A 4.2-kilobase cryptic Bacteroides plasmid, pB8-51, is found in several colonic Bacteroides species. To determine whether pB8-51 is mobilized by any of the known Bacteroides conjugal elements, we constructed an Escherichia coli-Bacteroides shuttle vector, pVAL-1, which contains pB8-51. We constructed Bacteroides uniformis 0061 derivatives which carry pVAL-1 and various Bacteroides conjugal elements. The Bacteroides conjugal elements tested were six conjugal tetracycline resistance (Tcr) elements (which appear to be chromosomal), i.e., Tcr ERL, Tcr V479, Tcr Emr ERL, Tcr Emr 12256, Tcr Emr DOT, and Tcr Emr CEST, and the conjugal erythromycin resistance (Emr) plasmid pBF4. These Tcr conjugal elements have not been extensively characterized, except for Tcr ERL. All six Tcr elements tested mobilized pVAL-1 at high frequency (10(-3) to 10(-5)) from one Bacteroides strain to another or from a Bacteroides strain to E. coli. Pregrowth of the donors (containing one of the Tcr elements and pVAL-1) in 1 microgram of tetracycline per ml enhanced the transfer of pVAL-1 by 20- to 10,000-fold, depending on which Tcr element was present in the donor. An Ems derivative of pBF4 (pBF4 delta E2) mobilized pVAL-1 from one Bacteroides strain to another at a frequency of 10(-4) but did not mobilize pVAL-1 from a Bacteroides strain to E. coli as efficiently. Thus the Tcr conjugal elements and pBF4 recognize a mobilization region on pB8 51. PMID- 3343222 TI - Bioenergetics of methanogenesis from acetate by Methanosarcina barkeri. AB - Methane formation from acetate by resting cells of Methanosarcina barkeri was accompanied by an increase in the intracellular ATP content from 0.9 to 4.0 nmol/mg of protein. Correspondingly, the proton motive force increased to a steady-state level of -120 mV. The transmembrane pH gradient however, was reversed under these conditions and amounted to +20 mV. The addition of the protonophore 3,5,3',4'-tetrachlorosalicylanilide led to a drastic decrease in the proton motive force and in the intracellular ATP content and to an inhibition of methane formation. The ATPase inhibitor N,N'-dicyclohexylcarbodiimide stopped methanogenesis, and the intracellular ATP content decreased. The proton motive force decreased also under these conditions, indicating that the proton motive force could not be generated from acetate without ATP. The overall process of methane formation from acetate was dependent on the presence of sodium ions; upon addition of acetate to cell suspensions of M. barkeri, a transmembrane Na+ gradient in the range of 4:1 (Na+ out/Na+ in) was established. Possible sites of involvement of the Na+ gradient in the conversion of acetate to methane and carbon dioxide are discussed. Na+ is not involved in the CO dehydrogenase reaction. PMID- 3343221 TI - Inhibition of the SOS response of Escherichia coli by the Ada protein. AB - Induction of the adaptive response by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) caused a decrease in the UV-mediated expression of both recA and sfiA genes but not of the umuDC gene. On the other hand, the adaptive response did not affect the temperature-promoted induction of SOS response in a RecA441 mutant. The inhibitory effect on the UV-triggered expression of the recA and sfiA genes was not dependent on either the alkA gene or the basal level of RecA protein, but rather required the ada gene. Furthermore, an increase in the level of the Ada protein, caused by the runaway plasmid pYN3059 in which the ada gene is regulated by the lac promoter, inhibited UV-mediated recA gene expression even in cells to which the MNNG-adaptive treatment had not been applied. This inhibitory effect of the adaptive pretreatment was not observed either in RecBC- strains or in RecBC mutants lacking exonuclease V-related nuclease activity. However, RecF- mutants showed an adaptive response-mediated decrease in UV-promoted induction of the recA gene. PMID- 3343223 TI - Chlamydia parasitism: ultrastructural characterization of the interaction between the chlamydial cell envelope and the host cell. AB - Ultrastructural analysis of the growth cycles of Chlamydia trachomatis and Chlamydia psittaci showed that the chlamydial cell envelope became rigid and septated at the time of the reorganization from reticulate to elementary body. This process occurred in the immediacy of the inclusion membrane and in close proximity with the mitochondria or the endoplasmic reticulum of the host cell. PMID- 3343224 TI - Methanol production by Mycobacterium smegmatis. AB - Mycobacterium smegmatis cells produce [3H]methanol when incubated with [methyl 3H]methionine. The methanol is derived from S-adenosylmethionine rather than methyltetrahydrofolate. M. smegmatis cells carboxymethylate several proteins, and some of the methanol probably results from their demethylation, but most of the methanol may come from an unidentified component with a high gel mobility. Although methanol in the medium reached 19 microM, it was not incorporated into the methylated mannose polysaccharide, a lipid carrier in this organism. PMID- 3343225 TI - Mechanism of glucocorticoid receptor down-regulation by glucocorticoids. AB - The effect of glucocorticoids on the regulation of glucocorticoid receptor mRNA was studied in two different cell lines, human IM-9 lymphocytes and rat pancreatic acinar AR42J cells. Using a glucocorticoid receptor cDNA probe, glucocorticoid receptor mRNA was examined by Northern blot hybridization and quantitated by slot-blot hybridization. In IM-9 and AR42J cells, dexamethasone decreased steady-state glucocorticoid receptor mRNA levels to approximately 50% of control. This decrease occurred with a one-half time of 3 h for IM-9 cells and 6 h for AR42J cells. Dexamethasone was the most potent steroid tested with a one half maximal effect occurring at 10 nM and a maximal effect occurring at 100 nM. Glucocorticoid receptor mRNA half-life and gene transcription were then studied to determine the mechanism of decreased mRNA levels. The glucocorticoid mRNA half life was approximately 120 min in IM-9 cells and 240 min in AR42J cells; these rates were not affected by dexamethasone treatment. In contrast, the rate of glucocorticoid gene transcription as measured by run-on assays in IM-9 cells was decreased to 50 +/- 6% of control by dexamethasone. These results indicate therefore that glucocorticoids regulate glucocorticoid receptor mRNA levels by influencing gene transcription. PMID- 3343226 TI - Characterization of the thyroid hormone transport system of isolated hepatocytes. AB - Transport of 3,5-[3'-125I]triiodo-L-thyronine ([125I]T3) was studied in isolated rat liver hepatocytes. T3 transport was temperature-sensitive, the initial velocity of uptake, at low substrate concentration, was 60 times higher at 25 degrees C than at 0 degrees C. The activation energy of cellular uptake (26 kcal/mol) was different from that of binding to cytosolic proteins (6 kcal/mol), indicating that the latter was not the rate-limiting step. Uptake obeyed simple Michaelis-Menten kinetics, with an apparent Km of 0.34 microM and a Vmax of 0.15 fmol/min/cell at 25 degrees C. No simple diffusion occurred. Unlabeled T3, L thyroxine (T4), 3,5,3'-triiodo-D-thyronine, and triiodothyroacetic acid inhibited T3 uptake with Kl values of 0.32, 1.4, 4.1, and 5.4 microM, respectively, indicating specificity of uptake which was different from specificity of intracellular binding sites. [125I]T4 was also taken up by a saturable process (Km = 0.65 microM and Vmax = 0.16 fmol/min/cell at 25 degrees C). T3 was a better competitor than T4 for the uptake of [125I]T4, indicating that both hormones were taken up by the same carrier system. Metabolic inhibitors had either no effect on T3 uptake or inhibitory effects unrelated to cellular ATP depletion. Uptake was not affected by modification of the membrane potential or the sodium ion gradient. T3 and T4 uptake was pH-dependent. It is suggested that the un-ionized 4'-OH form of the hormones was preferentially taken up. Inhibition of uptake by various compounds was compared to inhibition of thyroid hormone binding to transthyretin, nuclear receptor, and cytosolic-binding proteins. We conclude that, in freshly isolated hepatocytes, thyroid hormones are taken up by a saturable, stereospecific, Na+-independent carrier system. PMID- 3343227 TI - Specificity of binding of NH2-terminal residue of proteins to ubiquitin-protein ligase. Use of amino acid derivatives to characterize specific binding sites. AB - Previous studies have indicated that at least part of the selection of proteins for degradation takes place at a binding site on ubiquitin-protein ligase, to which the protein substrate is bound prior to ligation to ubiquitin. It was also shown that proteins with free NH2-terminal alpha-NH2 groups bind better to this site than proteins with blocked NH2 termini (Hershko, A., Heller, H., Eytan, E., and Reiss, Y. (1986) J. Biol. Chem. 261, 11992-11999). In the present study, we used simple derivatives of amino acids, such as methyl esters, hydroxamates, or dipeptides, to examine the question of whether the protein binding site of the ligase is able to distinguish between different NH2-terminal residues of proteins. Based on specific patterns of inhibition of the binding to ligase by these derivatives, three types of protein substrates could be distinguished. Type I substrates are proteins that have a basic NH2-terminal residue (such as ribonuclease and lysozyme); these are specifically inhibited by derivatives of the 3 basic amino acids (His, Arg, and Lys) with respect to degradation, ligation to ubiquitin, and binding to ligase. Type II substrates (such as beta lactoglobulin or pepsinogen, that have a Leu residue at the NH2 terminus) are not affected by the above compounds, but are specifically inhibited by derivatives of bulky hydrophobic amino acids (Leu, Trp, Phe, and Tyr). In these cases, the amino acid derivatives apparently act as specific inhibitors of the binding of the NH2 terminal residue of proteins, as indicated by the following observations: (a) derivatives in which the alpha-NH2 group is blocked were inactive and (b) in dipeptides, the inhibitory amino acid residue had to be at the NH2-terminal position. An additional class (Type III) of substrates comprises proteins that have neither basic nor bulky hydrophobic NH2-terminal amino acid residues; the binding of these proteins is not inhibited by homologous amino acid derivatives that have NH2-terminal residues similar to that of the protein. It is concluded that Type I and Type II proteins bind to distinct and separate subsites of the ligase, specific for basic or bulky hydrophobic NH2-terminal residues, respectively. On the other hand, Type III proteins apparently predominantly interact with the ligase at regions of the protein molecule other than the NH2 terminal residue. PMID- 3343228 TI - Microsomal preparation from an animal tissue catalyzes release of carbon monoxide from a fatty aldehyde to generate an alkane. AB - Alkanes are widely distributed in nature and impaired alkane synthesis was implicated in certain neurological disorders. However, the mechanism of synthesis of alkanes in animals is unknown. Our search to find a convenient animal tissue to study alkane biosynthesis resulted in the finding that the uropygial gland (a modified sebaceous gland) of the eared grebe (Podiceps nigricollis) produces large amounts of alkanes. These alkanes, which constitute 35-41% of the total lipid produced, are mainly C21, C23, C25, and C27 n-alkanes. Cell free homogenates of this tissue synthesized alkanes from both fatty acid and aldehyde in the absence of O2. Differential centrifugation of the homogenates indicated that this activity was located in the microsomal fraction. With isolated microsomes conversion of fatty acid to alkane required CoA, ATP, and NADH whereas conversion of an aldehyde to alkane did not require the addition of cofactors. That the final step in alkane synthesis is a decarbonylation was shown by the stoichiometric production of heptadecane and CO from octadecanal. CO was identified by adsorption to RhCl [(C6H6)3P]3 and oxidation of the trapped CO to CO2 by watergas shift reaction. The enzyme preparation also catalyzed incorporation of 14C from 14CO into octadecanal showing the reversible nature of the decarbonylase. This decarbonylase had a sharp pH optimum at 7.0, a Kapp of 180 microM and a V1/2 of 90 rho mol/min/mg protein for octadecanal. The enzyme was inhibited by the metal chelators EDTA, O-phenanthroline, and 8 hydroxyquinoline, but not by KCN. It was stimulated nearly 3-fold by 5 microM 2 mercaptoethanol and inhibited by the presence of O2. During the conversion of [1 3H]octadecanal to heptadecane, 3H was lost to water and 3H from 3H2O was incorporated into the alkane generated from unlabeled octadecanal. The mechanism of the decarbonylation and the nature of the enzyme remain to be elucidated. PMID- 3343230 TI - Binding of soluble fibronectin and its subsequent incorporation into the extracellular matrix by early and late passage human skin fibroblasts. AB - The specific binding of soluble 125I-labeled human plasma fibronectin (125I-HFN P) to confluent cultures of early and late passage human skin fibroblasts was investigated. Previous studies of HFN-P bound to fibroblast cell layers indicated that HFN-P was present in the cultures in two separate pools, distinguishable on the basis of their solubility in 1% deoxycholate. Pool I contained deoxycholate soluble fibronectin (cell-associated), whereas Pool II contained deoxycholate insoluble fibronectin (matrix-associated). Time course studies indicated that HFN P was initially incorporated into Pool I and then accumulated into Pool II (McKeown-Longo, P.J., and Mosher, D.F. (1983) J. Cell Biol. 97, 466-472). Examination of the kinetics of 125I-HFN-P binding to Pool I of early and late passage cultures revealed that both cultures required 2-4 h to approach steady state conditions. Other kinetic studies showed that the rates of loss of 125I-HFN P from either Pool I or Pool II were similar for both cultures. However, the late passage cultures bound greater than twice as much fibronectin into Pool I, per cell, than the early passage cultures. This difference was not related to a difference in the level of endogenously produced fibronectins accumulating in the medium. Late passage cultures incorporated 125I-HFN-P into the deoxycholate insoluble Pool at an average rate 2.6 times greater than early passage cultures. The late passage cultures also chased a greater percent of their Pool I-bound fibronectin into Pool II and a lower percent into the chase medium. These results indicate that early and late passage cultures of human fibroblasts exhibit differences in the binding of soluble fibronectin and in the extent to which they incorporate soluble fibronectin into the extracellular matrix. PMID- 3343229 TI - CAMP-dependent protein kinase of sea urchin sperm phosphorylates sperm histone H1 on a single site. AB - The phosphorylation of sperm specific histone H1 in the sea urchin Strongylocentrotus purpuratus occurs both in vivo and in vitro on a single serine site in the sequence Arg-Lys-Gly-Ser(P)-Ser-Asn-Ala-Arg. This is a preferred sequence for cAMP-dependent protein kinase. The in vitro phosphorylation is completely dependent on cAMP and is inhibited by the peptide protein kinase inhibitor. The protein kinase inhibitor H-8 blocks the in vivo phosphorylation of H1 without damaging motility, the acrosome reaction or the ability of sperm to fuse with and activate eggs. PMID- 3343231 TI - Peptidyl sulfonium salts. A new class of protease inhibitors. AB - The possibility has been examined that peptidylmethyl sulfonium salts might affinity label proteases by an alkyl transfer from sulfur to an active center residue. The synthesis of a number of agents of this type is described as well as initial results of their effect on cysteinyl proteases, papain and cathepsin B. These are readily inactivated by reagents in which the peptidyl portion contains features that promote binding to the proteases such as a penultimate phenylalanine residue. Irreversible inactivation ensues by transfer of the peptidyl portion, not methyl groups. Peptidylmethyl sulfonium salts lose a proton to form an ylide structure which may be the prevalent form at physiological pH values. The ylide may also be the active affinity labeling form of the reagent since the rate of inactivation of cathepsin B increases with pH. In contrast, the action of another affinity labeling reagent for cathepsin B, benzyloxycarbonyl Phe-AlaCHN2, a diazomethyl ketone, is relatively independent of pH. PMID- 3343232 TI - Domain interaction in rabbit muscle pyruvate kinase. I. Effects of ligands on protein denaturation induced by guanidine hydrochloride. AB - The structural stability of rabbit muscle pyruvate kinase was examined. The unfolding of pyruvate kinase was induced by guanidine hydrochloride, and the process was monitored by spectroscopic techniques (fluorescence and UV absorption) and hydrodynamic measurements (sedimentation velocity, sedimentation equilibrium, densimetry, and viscometry). The spectroscopic techniques revealed that the unfolding of pyruvate kinase induced by guanidine hydrochloride is not a simple cooperative process. This suggests that different regions of pyruvate kinase are unfolding with different efficiencies in response to the denaturant. These regions are most likely related to the domain structures observed by x-ray crystallography. In the presence of L-phenylalanine, the allosteric inhibitor, the denaturation process became more cooperative, and the enzyme dissociated and unfolded at a higher denaturant concentration. The binding of phenylalanine also induced a structural change in the enzyme, rendering it more susceptible to tryptic digestion. One of the peptides, the production rate of which was increased, was isolated and sequenced. Its N terminus is located at the interface between two domains, one of which contains the active site. This evidence indicates structural changes, probably involving domain-domain interaction, for pyruvate kinase in response to phenylalanine binding. PMID- 3343233 TI - Domain interaction in rabbit muscle pyruvate kinase. II. Small angle neutron scattering and computer simulation. AB - The effects of ligands on the structure of rabbit muscle pyruvate kinase were studied by small angle neutron scattering. The radius of gyration, RG, decreases by about 1 A in the presence of the substrate phosphoenolpyruvate, but increases by about the same magnitude in the presence of the allosteric inhibitor phenylalanine. With increasing pH or in the absence of Mg2+ and K+, the RG of pyruvate kinase increases. Hence, there is a 2-A difference in RG between two alternative conformations. Length distribution analysis indicates that, under all experimental conditions which increase the radius of gyration, there is a pronounced increase observed in the probability for interatomic distance between 80 and 110 A. These small angle neutron scattering results indicate a "contraction" and "expansion" of the enzyme when it transforms between its active and inactive forms. Using the alpha-carbon coordinates of crystalline cat muscle pyruvate kinase, a length distribution profile was calculated, and it matches the scattering profile of the inactive form. These observations are expected since the crystals were grown in the absence of divalent cations (Stuart, D. I., Levine, M., Muirhead, H., and Stammers, D. K. (1979) J. Mol. Biol. 134, 109-142). Hence, results from neutron scattering, x-ray crystallographic, and sedimentation studies (Oberfelder, R. W., Lee, L. L.-Y., and Lee, J.C. (1984) Biochemistry 23, 3813-3821) are totally consistent with each other. With the aid of computer modeling, the crystal structure has been manipulated in order to effect changes that are consistent with the conformational change described by the solution scattering data. The structural manipulation involves the rotation of the B domain relative to the A domain, leading to the closure of the cleft between these domains. These manipulations resulted in the generation of new sets of atomic (C-alpha) coordinates, which were utilized in calculations, the result of which compared favorably with the solution data. PMID- 3343234 TI - Purification of a paracrine factor, P-Mod-S, produced by testicular peritubular cells that modulates Sertoli cell function. AB - A testicular paracrine factor, P-Mod-S, was purified from conditioned medium obtained from serum-free cultures of peritubular cells. Stimulation of testicular transferrin production by cultured Sertoli cells was utilized as a bio-assay for P-Mod-S. A bioactive protein with an apparent molecular weight of 50,000 under physiological conditions was isolated by high pressure size exclusion chromatography. P-Mod-S was found to have an affinity for heparin and bound to a heparin affinity column. Two forms of P-Mod-S were purified with reverse-phase chromatography. The less hydrophobic form was referred to as P-Mod-S (A) and is a 56,000 molecular weight protein. The more hydrophobic form was referred to as P Mod-S (B) and is a 59,000 molecular weight protein. Purification of P-Mod-S (A) and P-Mod-S (B) from peritubular cell-radiolabeled secreted proteins revealed that both proteins contain radioactivity. This result demonstrates active synthesis and secretion of P-Mod-S by peritubular cells. Although the amino acid composition of the two proteins indicates distinct differences in the content of several amino acids, the relationship of P-Mod-S (A) and P-Mod-S (B) is unknown at present. A greater than 1000-fold increase in the specific activity of P-Mod-S was achieved with the purification procedure utilized. P-Mod-S can account for essentially all the bioactivity present in crude peritubular cell-secreted protein preparations. The effects of the two forms of P-Mod-S on both transferrin and androgen-binding protein production by Sertoli cells was examined. Purified forms of P-Mod-S were found to have a greater effect on Sertoli cell function than any individual regulatory agent previously known to influence the cell, including follicle-stimulating hormone. The significance of peritubular cell Sertoli cell interactions mediated via P-Mod-S to spermatogenesis and testicular function is discussed, as well as insight provided into general mesenchymal epithelial cell interactions. PMID- 3343235 TI - Retinol-binding protein synthesis and secretion by the rat visceral yolk sac. Effect of retinol status. AB - Studies were conducted to explore in rats the role of retinol in the regulation of the synthesis and secretion of retinol-binding protein (RBP) by the visceral yolk sac compared to the liver. Previous studies have shown that in retinol deficiency, hepatic RBP secretion is specifically inhibited, whereas hepatic RBP synthesis rate is unchanged. Retinol-depleted, retinoic acid-supplemented female rats were mated, and maternal liver, fetal liver, and visceral yolk sac were obtained at 14 days of gestation (retinol-depleted group). A group of identically treated, retinol-depleted rats were repleted with retinol on the 14th day of gestation, and the same tissues were collected 6 h later (retinol-repleted group). Normal female rats were used as controls. RBP was assayed by radioimmunoassay and RBP mRNA levels by RNase protection assay using a rat RBP cDNA clone. RBP levels in the visceral yolk sac were elevated 10-fold in the retinol-depleted as compared to the control rats and had declined to near normal values in the retinol-repleted animals. The relative levels of RBP mRNA in the visceral yolk sac were very similar in all three groups of rats. Thus, as in the liver, in the visceral yolk sac retinol deficiency inhibits RBP secretion without altering RBP mRNA levels. In the visceral yolk sac, as in the liver, retinol status appears to regulate RBP secretion specifically, without affecting the rate of RBP biosynthesis. PMID- 3343236 TI - Mosaic evolution of prepropancreatic polypeptide. II. Structural conservation and divergence in pancreatic polypeptide gene. AB - We demonstrated that nucleotide and amino acid sequences in the carboxyl-terminal regions of rat, mouse, and human prepropancreatic polypeptide exhibit a high degree of divergence, whereas the amino-terminal domains are highly conserved. To understand the molecular basis of this divergence and conservation, we determined the nucleotide sequence of the rat pancreatic polypeptide gene from an islet genomic library and compared it with that of the human gene. Exon 2 of the rat gene encodes the signal peptide and pancreatic polypeptide, exon 3 encodes the carboxyl-terminal region, and exons 1 and 4 encode the 5'- and 3'- untranslated regions of the mRNA, respectively. Exons 1 and 2 of rat and human genes are well conserved. The rat and human genes, however, have exons 3 and 4 of different lengths and heterologous nucleotide sequences. Mutational accumulation in exons 3 and 4 and intron 3 of the rat gene appears to have caused splice junction sliding and translational frameshift, resulting in a structural divergence in the carboxyl-terminal region. Available evidence indicates that the mosaicism of structural conservation and divergence in pancreatic polypeptide genes may have been caused by a difference in the evolutionary rates of the genomic regions. PMID- 3343237 TI - The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. AB - Hepatocytes obtained from rats fed a choline-deficient diet for 3 days were cultured in a medium +/- choline (100 microM) or methionine (200 microM). We investigated how choline deficiency affected hepatic lipogenesis, apolipoprotein synthesis, and lipoprotein secretion. The mass of triacylglycerol and phosphatidylcholine secreted was increased about 3-fold and 2-fold, respectively, by the addition of either choline or methionine to the cultured cells. Similarly, a 3-fold stimulation in the secretion of [3H]triacylglycerol and [3H]phosphatidylcholine derived from [3H]oleate was observed after the addition of choline or methionine. Fractionation of secreted lipoproteins by ultracentrifugation revealed that the reduced secretion of triacylglycerol and phosphatidylcholine from choline-deficient cells was mainly due to impaired secretion of very low density lipoproteins (VLDL) (but not high density lipoproteins (HDL)). Fluorography of L-[4,5-3H]leucine-labeled lipoproteins showed a remarkable inhibition of VLDL secretion by choline deficiency. The addition of choline or methionine stimulated the synthesis of phosphatidylcholine and increased the cellular phosphatidylcholine levels to that in normal cells. While there was little effect of choline on the synthesis and amount of cellular phosphatidylethanolamine, the addition of methionine diminished cellular phosphatidylethanolamine levels. Choline deficiency did not change the rate of incorporation of L-[4,5-3H]leucine into cellular VLDL apolipoproteins, nor the rate of disappearance of radioactivity from L-[4,5-3H]leucine-labeled cellular apoB, apoE, and apoC. These results suggest that hepatic secretion of VLDL, but not HDL, requires active phosphatidylcholine biosynthesis. Secondly, the inhibitory effect of choline deficiency on VLDL secretion can be compensated by the methylation of phosphatidylethanolamine. PMID- 3343238 TI - Biosynthesis of placental alkaline phosphatase and its post-translational modification by glycophospholipid for membrane-anchoring. AB - The biosynthesis and post-translational modification of placental alkaline phosphatase were studied in human choriocarcinoma cells, JEG-3. Pulse-chase experiments with [35S]methionine demonstrated that placental alkaline phosphatase was synthesized as a major precursor form with Mr 63,000, which was then converted to a mature form with Mr 66,000, by processing of its N-linked oligosaccharides from the high-mannose type to the complex type. In addition, the two forms of the protein were found to be modified by a glycophospholipid, components of which were characterized by metabolic incorporation into placental alkaline phosphatase of 3H-labeled compounds such as myo-inositol, palmitic acid, stearic acid, mannose, glucosamine, and ethanolamine. When placental alkaline phosphatase labeled with these compounds was treated with phosphatidylinositol specific phospholipase C or papain, the phospholipase C removed only the 3H labeled fatty acids, whereas papain, that is known to cleave the C-terminal region, released all the radioactive glycolipid components including [3H]ethanolamine. More detailed analysis with shorter pulse-chase experiments demonstrated that placental alkaline phosphatase was primarily synthesized as a form with Mr 64,500 which was not yet labeled with [3H]palmitic acid. This form was converted by papain digestion to the above-mentioned major precursor with Mr 63,000. Taken together, these results suggest that placental alkaline phosphatase is initially synthesized as the precursor with Mr 64,500, which is immediately converted to the intermediate form with Mr 63,000 by simultaneously occurring proteolysis of the C terminus and replacement by the glycophospholipid, and finally to the mature form with Mr 66,000 by terminal glycosylation of its N linked oligosaccharides. The glycophospholipid thus attached is considered to function as the membrane-anchoring domain of placental alkaline phosphatase. PMID- 3343239 TI - Characterization of ovarian gonadotropin receptor. Monomer and associated form of the receptor. AB - We have purified luteinizing hormone/human choriogonadotropin (hCG) receptor from rat ovary by sequential affinity column on wheat germ lectin-Sepharose and hCG Sepharose chromatography. The purified receptor, previously identified as a single protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) (Kusuda, S., and Dufau, M.L. (1986) J. Biol. Chem. 261, 16161-16168), was further characterized by radioiodination with 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycouril, and column chromatography on wheat germ lectin Sepharose. Autoradiography of SDS-PAGE analysis under reducing conditions showed a single radiolabeled band of Mr = 80,000. The radioiodinated receptors treated with peptide:N-glycosidase F migrated at Mr = 54,000. Treatment with neuraminidase alone caused only a minor reduction in molecular weight, and subsequent treatment with endo-alpha-N-acetyl-D-galactosaminidase had little further effect on the receptor. When the radioiodinated receptor was analyzed by fast protein liquid chromatography, a single broad peak was eluted with Mr of approximately 350,000. The higher Mr of radioiodinated receptors than that of native receptors (Mr = 190,000 dimeric form) could be due to the aggregation of labeled molecules. These complexes dissociated into the monomeric form in the presence of SDS. To determine whether the monomers can bind hormone, the purified unlabeled receptors resolved with SDS were electroblotted to nitrocellulose membranes and incubated with 125I-hCG. Autoradiograms of the blots showed a band of monomer (Mr = 78,000) as well as one of dimer (Mr approximately 150,000). These studies have demonstrated that the luteinizing hormone/hCG receptors are predominantly N-linked glycosylated and suggest that the native receptor is a dimer of identical hormone binding subunits associated by noncovalent interactions. Although the individual subunits can bind hormone, it is conceivable that the dimeric form is necessary for signal transduction. PMID- 3343240 TI - Identification of ADP in the iron-sulfur flavoprotein trimethylamine dehydrogenase. AB - Analysis of the 2.4-A resolution electron density map of trimethylamine dehydrogenase has revealed the unexpected presence of one molecule of ADP/subunit. This binding has been confirmed chemically. The binding site is located at the analogous position of the ADP moiety of FAD in glutathione reductase, the FAD and NADPH binding domains of which resemble two of the domains of trimethylamine dehydrogenase. Comparison of the environments of the ADP moieties in the two proteins indicates that 32 residues in 6 peptides are in equivalent positions with a root mean square deviation for C alpha positions of 1.11 A. Twelve of these amino acids are identical, based on the electron density derived "x-ray" sequence of trimethylamine dehydrogenase. Detailed analysis of the environment of the ADP moiety indicates that most of the conserved residues are not in direct contact with the cofactor. Some of them probably represent the "fingerprint" of the beta alpha beta binding fold found in dinucleotide binding proteins, but the remaining conserved residues may indicate a closer evolutionary relationship between these two proteins. PMID- 3343242 TI - Molecular modeling reveals the possible importance of a carbonyl oxygen binding pocket for the catalytic mechanism of p-hydroxybenzoate hydroxylase. AB - p-Hydroxybenzoate hydroxylase catalyzes the hydroxylation of an aromatic substrate and uses flavin as a cofactor. The reaction probably occurs via a flavin 4a-hydroperoxide intermediate. In this study the crystal structure of 4a,5 epoxyethano-3-methyl-4a,5-dihydrolumiflavin, an analogue of the flavin 4a hydroperoxide intermediate, was fitted to the active site in the crystal structure of the p-hydroxybenzoate hydroxylase-3,4-dihydroxybenzoate complex. This model of an important catalytic intermediate fitted very well in the active site of p-hydroxybenzoate hydroxylase. The most striking result was that whereas with the normal flavin, the 0-4 of the flavin ring makes only poor hydrogen bonds with the protein, with the flavin 4a-hydroperoxide analogue, the same 0-4 makes strong hydrogen bonds with the NH groups of Gly-46 and Val-47. These two NH groups form a carbonyl oxygen binding pocket which has a geometry almost identical to the oxyanion hole found in several proteases. The possible consequences of this model for the reaction mechanism of p-hydroxybenzoate hydroxylase are discussed. PMID- 3343241 TI - Solubilization, purification, and characterization of a membrane-bound phospholipase A2 from the P388D1 macrophage-like cell line. AB - The release of free arachidonic acid from membrane phospholipids is believed to be the rate-controlling step in the production of the prostaglandins, leukotrienes, and related metabolites in inflammatory cells such as the macrophage. We have previously identified several different phospholipases in the macrophage-like cell line P388D1 potentially capable of controlling arachidonic acid release. Among them, a membrane-bound, alkaline pH optimum, Ca2+-dependent phospholipase A2 is of particular interest because of the likelihood that the regulatory enzyme has these properties. This phospholipase A2 has now been solubilized from the membrane fraction with octyl glucoside and partially purified. The first two steps in this purification are butanol extractions that yield a lyophilized, stable preparation of phospholipase A2 lacking other phospholipase activities. This phospholipase A2 shows considerably more activity when assayed in the presence of glycerol, regardless of whether the substrate, dipalmitoylphosphatidylcholine, is in the form of sonicated vesicles or mixed micelles with the nonionic surfactant Triton X-100. Glycerol (70%) increases both the Vmax and the Km with both substrate forms, giving a Vmax of about 15 nmol min 1 mg-1 and an apparent Km of about 60 microM for vesicles and a Vmax of about 100 nmol min-1 mg-1 and an apparent Km of about 1 mM for mixed micelles. Vmax/Km is slightly greater for vesicles than for mixed micelles. The lyophilized preparation of the enzyme is routinely purified about 60-fold and is suitable for evaluating phospholipase A2 inhibitors such as manoalide analogues. Subsequent steps in the purification are acetonitrile extraction followed by high performance liquid chromatography on an Aquapore BU-300 column and a Superose 12 column. This yields a 2500-fold purification of the membrane-bound phospholipase A2 with a 25% recovery and a specific activity of about 800 nmol min-1 mg-1 toward 100 microM dipalmitoylphosphatidylcholine in mixed micelles. When this material was subjected to analysis on a Superose 12 sizing column, the molecular mass of the active fraction was approximately 18,000 daltons. PMID- 3343243 TI - Theoretical study of the product specificity in the hydroxylation of camphor, norcamphor, 5,5-difluorocamphor, and pericyclocamphanone by cytochrome P-450cam. AB - The hydroxylations of d-camphor, norcamphor, pericyclocamphanone, and 5,5 difluorocamphor by cytochrome P-450cam have been examined using theoretical methods to identify and characterize properties which determine product specificity. Experimental results indicate that each molecule is hydroxylated with quite different regio-specificity when metabolized by P-450cam. This result is surprising in view of their overall structural similiarity. Herein we report the results of calculations on d-camphor and three of its analogues which suggest that all of these molecules should, when metabolized by P-450cam, form hydroxylation products and predict the product distribution for each. Our conclusions are based on two fundamental criteria which are consistent with a generally accepted radical mechanism in determining product specificity in these molecules: 1) relative heats of formation of the radicals formed by abstracting a hydrogen, and 2) orientation of the substrate molecule with respect to the putative active oxygen species bound to iron. Our results explain the experimental observations for camphor and 5,5-difluorocamphor but disagree with original published results for norcamphor and pericyclocamphanone. In light of our results, new experiments have been performed for norcamphor and the original data reexamined for pericyclocamphanone. Our predictions have recently been experimentally confirmed for norcamphor, and unpublished data (Dr. S. Sligar) suggest that the same is true for pericyclocamphanone. PMID- 3343244 TI - Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells. AB - Adrenodoxin is an iron-sulfur protein serving as an electron transport intermediate for two mitochondrial steroidogenic cytochromes P450. We have cloned and sequenced three human adrenal adrenodoxin cDNAs. The longest 5'-untranslated region was 131 bases long, and the coding sequences, identical in all three clones, predict a preprotein of 180 amino acids. The 3'-untranslated regions were 235, 596, and 776 bases long due to the presence of alternate polyadenylation sites. RNA transfer blots showed multiple size species of adrenodoxin mRNA consistent with finding multiple polyadenylation sites. Similar sized cross hybridizing RNA species are found abundantly in the adrenal and testis and to a lesser degree in RNA from human fetal brain, spleen, placenta, kidney, liver, and intestine, as well as in cultured fibroblasts, suggesting the same or a very similar iron-sulfur protein is found in mitochondria of nonsteroidogenic tissues. JEG-3 cells, a transformed progesterone-producing line of trophoblastic origin, accumulate mRNAs for cytochrome P450scc (the mitochondrial cholesterol side-chain cleavage enzyme), adrenodoxin, and the fos oncogene when stimulated with 8-bromo cyclic AMP. Addition of actinomycin D to such cultures blocked cAMP-induced accumulation of mRNAs for cytochrome P450scc and adrenodoxin. Addition of cycloheximide or puromycin to such cultures substantially reduced basal levels and markedly attenuated the cAMP-induced accumulation of cytochrome P450scc mRNA, but augmented the accumulation of adrenodoxin and fos mRNAs in additive and multiplicative fashions, respectively. These data indicate that the cAMP-induced synthesis of the steroidogenic machinery is not wholly dependent on cycloheximide sensitive protein mediators. PMID- 3343245 TI - Proton NMR studies of human hemoglobin variants modified in the proximal side of beta heme pocket. Implications for the affinity control and cooperative mechanism. AB - Using high resolution proton NMR spectroscopy, we have investigated 10 human hemoglobin variants modified in the proximal side of the heme pocket in beta subunits. Comparative observation of several resonances in the spectra of liganded and unliganded hemoglobins allowed us to characterize the localization and nature of the structural perturbations induced by amino acid substitutions or chemical modification. The present data indicate that the structural perturbations are localized in the beta subunits, mainly in the tertiary domain surrounding the modification site. Analysis of the aromatic region of the liganded hemoglobin spectra gives substantial information for the assignment of the His-beta 97 C-2H resonance. Correlation of the spectroscopic observations with the functional characteristics of the studied hemoglobins demonstrates that structural factors localized in the proximal side of the heme pocket can control the ligand-iron interaction taking place on the other heme side. The structural perturbations induced by the modifications in the F or FG segments of the beta subunits do not extend to the distal side but rather to the alpha 1 beta 2 interface. This argues the existence of a gradient of tertiary structural stability, indicating a possible structural pattern of heme-heme interaction in the cooperativity control. PMID- 3343246 TI - The binding of L-valyl-L-tryptophan to crystalline thermolysin illustrates the mode of interaction of a product of peptide hydrolysis. AB - Crystallographic analysis of the binding of mercaptoacetyl-L-valyl-L-tryptophan to thermolysin suggests that this inhibitor is hydrolyzed by the crystalline enzyme. The apparent product of hydrolysis, L-valyl-L-tryptophan (Val-Trp), occupies the S1'-S2' subsites of the active site, not the S1-S1' subsites as observed previously for the dipeptide L-alanyl-L-phenylalanine (Ala-Phe). The difference in binding of Val-Trp and Ala-Phe is consistent with the specificity requirements and preferences of thermolysin. The binding of Val-Trp illustrates the mode of interaction of one of the products of peptide hydrolysis. High resolution crystallographic refinement indicates that the valyl amino group makes three hydrogen bonds to the enzyme and to solvent and, in addition, is 2.8 A from the carboxylate of Glu-143. This is the first instance in which a direct interaction has been observed between Glu-143 and the scissile nitrogen. As such, the study directly supports the mechanism of action for thermolysin proposed by Hangauer et al. (Hangauer, D. G., Monzingo, A. F., and Matthews, B. W. (1984) Biochemistry 23, 5730-5741) and, by analogy, indirectly supports the similar mechanism proposed for carboxypeptidase A (Monzingo, A. F., and Matthews, B. W. (1984) Biochemistry 23, 5724-5729). PMID- 3343248 TI - Evidence suggesting that the two forms of heme oxygenase are products of different genes. AB - Recently, we have reported on the presence of two forms of heme oxygenase in rat liver and testis microsomes, referred to as HO-1 and HO-2 (M. D. Maines, G. M. Trakshel, and R. K. Kutty (1986) J. Biol. Chem. 261, 411-419; G. M. Trakshel, R. K. Kutty, and M. D. Maines (1986) J. Biol. Chem. 261, 11131-11137). Although the two forms differed in several biochemical properties, we could not ascertain whether they represented two isozymes or whether they were isoforms of heme oxygenase. In the present study, we provide evidence suggesting that the two forms are isozymes and represent different gene products. We also provide data suggesting that HO-1 is the commonly known heme oxygenase form. The molecular weight and immunochemical properties of HO-1 and HO-2 did not vary depending on the tissue source examined, i.e. liver and testis. Major differences, however, were noted in the amino acid composition of the two forms including the presence of 3 cysteine/cystine residues in HO-2 only. Using antibody to HO-2, four testis clones and two liver clones were isolated, and one liver and one testis clone were sequenced. Both clones revealed a 274-base-pair insert, and the sequence of both inserts was the same. The validity of assignment was confirmed by matching a 14-amino-acid peptide obtained from purified HO-2 with the sequence. Approximately 43% amino acid homology was detected between the HO-2 insert and the published amino acid sequence of heme oxygenase. However, amino acid homology search revealed the presence of two regions of homology: one 22-mer sequence with only one unmatched amino acid, and one 10-mer sequence with one unmatched amino acid. Heme oxygenase appeared to be the HO-1 form, an assignment based on its amino acid sequence matching the sequence of 2 peptides obtained from purified HO 1 and the immunochemical properties of the cobalt-, hematin-, and bromobenzene induced rat liver enzyme. The secondary structure prediction analysis revealed an area of 100% structural homology with only 72% sequence homology. We predict this region may represent the catalytic site of the enzyme. PMID- 3343247 TI - Persistent estrogen induction of hepatic Xenopus laevis serum retinol binding protein mRNA. AB - Administration of estradiol-17 beta to male Xenopus laevis induces the hepatic mRNA coding for the serum retinol binding protein (RBP) approximately 10-fold, both in vivo and in primary liver cultures. Estrogen induction of RBP mRNA is completely blocked by the anti-estrogen, hydroxytamoxifen. Testosterone administration reduces the elevated level of RBP mRNA observed in livers of female X. laevis to the constitutive level seen in livers of control male animals, and partially blocks the estrogen induction of RBP mRNA. Intracellular RBP mRNA levels therefore represent a balance between the opposing effects of estradiol-17 beta and testosterone. In marked contrast to the estrogen induction of vitellogenin mRNA, which requires the continuous presence of exogenous estrogen, induction of RBP mRNA persists for at least 4 months after a single injection of estrogen. Runoff transcription measurements demonstrate that persistent induction of RBP mRNA is due to an increased rate of RBP gene transcription. Administration of hydroxytamoxifen abolishes persistent induction of RBP mRNA, suggesting that residual hormone receptor complex plays a role in the persistent induction of RBP gene transcription. The persistent estrogen induction of RBP mRNA provides the first demonstration of long-term activation of the transcription of a hormone-responsive gene in response to a transient dose of a steroid hormone. PMID- 3343249 TI - Operator constitutive mutation of 3-hydroxy-3-methylglutaryl coenzyme A reductase promoter abolishes protein binding to sterol regulatory element. AB - Through substitution mutagenesis we identified the promoter elements responsible for basal expression and sterol-mediated repression of transcription of the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase, a rate-controlling enzyme of cholesterol biosynthesis. Mutant promoters containing 277 base pairs (bp) of reductase 5' flanking sequence were inserted into recombinant plasmids upstream of the coding region for bacterial chloramphenicol acetyltransferase. The plasmids were transfected into hamster fibroblasts, and transcription was measured in the presence and absence of sterols. Mutations in three regions that are known to bind nuclear proteins markedly reduced transcription. Mutation of another protein-binding region of 20 bp in length did not reduce transcription, but it did abolish sterol-mediated repression, producing an operator constitutive phenotype. This mutation also abolished protein binding to the corresponding 20 bp region of DNA as determined by footprinting assays. When a DNA fragment containing these 20 bp was inserted into the herpes simplex virus thymidine kinase promoter, sterol-mediated repression was observed. This sequence contains an octanucleotide that shows a 7/8-bp match with a previously identified regulatory sequence in repeat 2 of the low density lipoprotein receptor promoter, another sterol-repressible gene. We hypothesize that this octanucleotide, GTGGCGGTG, is the core binding site for a sterol-dependent protein that represses transcription. PMID- 3343250 TI - The role of mitochondrial matrix enzymes in the metabolism and toxicity of cysteine conjugates. AB - The submitochondrial localization and identity of enzymes which metabolize cysteine conjugates were investigated. Glutamine transaminase K was purified from rat kidney mitochondrial soluble fraction and was shown to be a cysteine conjugate beta-lyase. The purified mitochondrial enzyme is similar to the cytosolic glutamine transaminase K whose beta-lyase activity with S-(1,2 dichlorovinyl)-L-cysteine (DCVC) is regulated by concurrent transamination (Stevens, J. L., Robbins, J. D., and Byrd, R. A. (1986) J. Biol. Chem. 261, 15529 15537). However, beta-lyase activity in whole mitochondria is largely independent of regulation by cosubstrates for transamination suggesting that factors present in mitochondria are able to support the beta-lyase activity in the absence of added alpha-keto acid. Fractionation of mitochondria results in a loss of the independent beta-lyase activity. However, the majority of the beta-lyase activity can be recovered in the matrix if it is stimulated by the addition of alpha-keto gamma-methiolbutyrate. The data suggest that the regulation of beta-elimination by the competing transamination pathway is different for each substrate and that multiple beta-lyases may exist in rat kidney. S-(2-Benzothiazolyl)-L-cysteine (BTC) is a poor substrate for purified glutamine transaminase K from mitochondria and cytosol, but BTC is as active as DCVC in crude mitochondrial matrix suggesting that other enzymes may be present. In contrast to DCVC, with BTC as substrate, the beta-lyase activity of the purified enzyme and enzyme(s) in the mitochondrial matrix is largely alpha-keto acid-independent. The existence of multiple enzymes is also supported by the observation that alpha-keto acids which are not substrates for purified glutamine transaminase K from mitochondria and cytosol do stimulate beta-lyase activity in the mitochondrial matrix fraction. Mitoplasts were found to be sensitive to DCVC toxicity consistent with the matrix localization of beta-lyase activity. The possible role in cysteine conjugate toxicity of matrix enzyme regulation by alpha-keto acids is discussed. PMID- 3343251 TI - Effects of dietary protein intake on branched-chain keto acid dehydrogenase activity of the rat. Immunochemical analysis of the enzyme complex. AB - Polyclonal antibodies directed against the dihydrolipoyl transacylase (E2) and alpha subunit of branched-chain alpha-keto acid decarboxylase (E1 alpha) components of the bovine branched-chain keto acid dehydrogenase complex were shown to cross-react with the E2 and E1 alpha polypeptides of the enzyme complex of different rat tissues. Phosphorylation of the branched-chain keto acid dehydrogenase complex resulted in inhibition of enzyme activity concomitant with phosphate incorporation into the E1 alpha polypeptide. Phosphorylation of E1 alpha slowed its rate of migration through sodium dodecyl sulfate-polyacrylamide gels. This permitted resolution of the phosphorylated and unphosphorylated forms of E1 alpha on immunoblots. Liver and skeletal muscle mitochondria were prepared from rats consuming 6, 20, or 50% casein diets. The enzyme complex in mitochondria was measured by radioisotopic enzyme assay and immunoassay. Liver branched-chain keto acid dehydrogenase was 25% active in rats consuming 6% casein diets; whereas in rats consuming 20 or 50% casein diets, the liver enzyme was 82 or 100% active, respectively. Branched-chain keto acid dehydrogenase of muscle was 10, 13, and 22% active, respectively, in rats consuming 6, 20, and 50% casein diets. The amount of protein consumed by rats did not affect the total amount of the enzyme complex per unit of mitochondrial protein as measured by either the radioisotopic assay (enzyme activity) or the immunoassay. However, the protein intake of rats did affect activity of the enzyme kinase in liver. Liver branched chain keto acid dehydrogenase kinase was more active in rats consuming 6% casein than in those fed chow or 50% casein diets. The amount of protein consumed by rats thus influences the enzyme activity in liver and muscle by affecting the reversible phosphorylation mechanism and not by induction of branched-chain keto acid dehydrogenase. PMID- 3343252 TI - Novel subunit structure observed for noncooperative hemoglobin from Urechis caupo. AB - Tetrameric hemoglobin from the "fat innkeeper" worm Urechis caupo possesses a novel subunit arrangement having an "inside out" quaternary structure in that the G/H helices are located on the outer surface of the tetramer. A 5-A resolution crystal structure reveals that although the individual subunits are beta-like, having a distinct D helix and the general myoglobin fold, the subunit contacts are very different from those previously observed for hemoglobins. Furthermore, the hemoglobin from U. caupo is also quite different from the unusual hemoglobin tetramer from clam which also has its G/H helices on the outer surface but with the hemes in close proximity through E-F helical contacts (Royer, W. E., Jr., Love, W. E., and Fenderson, F. F. (1985) Nature 316, 277-280). PMID- 3343253 TI - Complete covalent structure of 60-kDa esterase isolated from 2,3,7,8 tetrachlorodibenzo-p-dioxin-induced rabbit liver microsomes. AB - The 60-kDa esterase was isolated from liver microsomes of 2,3,7,8 tetrachlorodibenzo-p-dioxin-induced rabbits and its complete amino acid sequence determined. Automated sequence analysis of intact protein, as well as characterization of the peptides obtained from enzymatic and chemical cleavages, led to the elucidation of the primary structure. The protein is a single polypeptide consisting of 539 residues and molecular weight 59,478. The active site serine is 195, and another diisopropylphospho binding site is at histidyl 441. Carbohydrate chains are attached at aspariginyl residues 61 and 363. Although 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment induces this esterase severalfold, the amino acid sequence of the induced enzyme is identical to that of the enzyme isolated from liver microsomes of untreated rabbits. The sequence of the microsomal esterase is 30% identical with the sequences of human serum cholinesterase and the acetylcholinesterase from Torpedo californica. There is also a close homology between the 60-kDa esterase and the COOH-terminal domain of bovine thyroglobulin. PMID- 3343255 TI - Physical and hydrodynamic factors affecting erythrocyte adhesion to polymer surfaces. AB - Using a flow cell design which ensures fully developed laminar flow, the influence of various hydrodynamic and physical factors in determining the extent of erythrocyte adhesion to various polymer surfaces has been examined. Specifically we have investigated the effect of exposure time, flow rate, erythrocyte concentration, and substrate surface tension on the extent of erythrocyte adhesion. The results indicate: (1) the extent of erythrocyte adhesion is most extensive on the more hydrophobic surfaces; (2) the rate of adhesion is higher on the more hydrophobic surfaces; (3) saturation coverage occurs after 7-10 min of exposure to the erythrocyte suspension for all substrates examined. No "lag-time" in the onset of adhesion was observed; (4) The level of saturation depends on the bulk erythrocyte concentration, increasing with increasing cell concentration; (5) the extent of adhesion decreases with an increase in flow rate; and (6) substrate surface defects such as roughness have a major effect on the pattern of erythrocyte adhesion. PMID- 3343254 TI - Purification and structural analysis of the modulator of the glucocorticoid receptor complex. Evidence that modulator is a novel phosphoglyceride. AB - Modulator is the low molecular weight heat-stable inhibitor of glucocorticoid receptor complex activation. We have purified modulator to apparent homogeneity from heated rat liver cytosol. This was accomplished using Sephadex G-15 gel filtration, Dowex 1 anion-exchange chromatography, and preparative silica high performance liquid chromatography. The modulator preparation was judged to be homogeneous by analytical silica high-performance liquid chromatography, two dimensional silica thin-layer chromatography, and proton nuclear magnetic resonance spectroscopy. The apparent concentration of modulator in rat liver cytosol is 6.5 microM. The purified modulator inhibits heat activation of the rat liver glucocorticoid-receptor complex and stabilizes the steroid binding ability of the unoccupied rat liver glucocorticoid receptor in a dose-dependent manner. At a concentration of 5-6.5 microM, modulator inhibits receptor activation and stabilizes the unoccupied receptor by 50%. At a concentration of 500-630 microM, sodium molybdate also inhibits receptor activation and stabilizes the unoccupied receptor by 50%. Thus, modulator appears to be the endogenous factor that exogenous sodium molybdate mimics in vitro. Chemical analysis of the purified modulator following two-dimensional silica thin-layer chromatography indicates that modulator is an aminophospholipid. Physical analysis of the purified modulator by infrared and nuclear magnetic resonance spectroscopy, as well as mass spectrometry, demonstrates that modulator is an ether aminophosphoglyceride. PMID- 3343256 TI - AES analysis of stainless steel corroded in saline, in serum and in vivo. AB - Auger electron spectroscopic (AES) studies were conducted to examine the surface film of stainless steel specimens which had been subjected to passive and anodic corrosion in vitro and in vivo. Anodic corrosion was accelerated by the application of a +500 mV (SCE) potential for 30 minutes. Experiments performed in 0.9% saline indicated little alteration in the nature of the surface film compared to a freshly prepared control specimen. Auger analysis of specimens in 10% serum or in vivo revealed that passive film thickness was dependent on the corrosive environment. The films of specimens immersed under freely corroding conditions in 10% serum or in vivo were similar to the control film. Accelerated corrosion performed in 10% calf serum resulted in significant film thickening. The thickest films were from accelerated corrosion in vivo. The mechanism for the altered surface films produced by corrosion in vivo or in serum as compared to saline needs to be investigated further. PMID- 3343257 TI - Interaction between erythrocytes and a perfluorochemical blood substitute. AB - Perfluorochemicals (PFCs) are being widely developed for use as erythrocyte substitutes to carry oxygen to tissue in acute crises. Oxypherol, a commercially available PFC preparation commonly used for animal tests, reduces erythrocyte deformability in the presence of plasma. This undesirable effect further complicates oxygen delivery by erythrocytes. Our experiments indicate that one or more plasma proteins must be present to observe Oxypherol-induced reduction in erythrocyte deformability, but the latter is not protein specific. Neither platelet activation nor enhanced protein adsorption could account for the mechanism of altered erythrocyte flexibility. Using fluorine-19 NMR, it was found that a small amount of Oxypherol droplets is adsorbed on the surface of the erythrocytes. The amount of adsorbed droplets increases when Oxypherol is incubated with the erythrocytes in the presence of plasma, in parallel with a decrease in erythrocyte deformability. Therefore, it seems likely that the loss of deformability of the erythrocytes is caused by the adsorption of small Oxypherol droplets on the erythrocytes. PMID- 3343258 TI - Hydrophilic microporous polyurethane versus expanded PTFE grafts as substitutes in the carotid arteries of dogs. A limited study. AB - A novel, microporous, hydrophilic polyether urethane-urea (PEUU) vascular graft was compared with expanded PTFE in the canine carotid artery. At implantation times ranging from 4 h to 6 months, all the PEUU grafts were found to be occluded while of the PTFE grafts, only those implanted for 1 week and 6 months were blocked. Histopathological analysis of the explanted grafts and their capsules revealed an ongoing inflammatory reaction at the anastomotic sites of the PEUU grafts. PMID- 3343259 TI - All-terrain vehicles. PMID- 3343260 TI - Comparison of replacement prostheses for segmental defects of bone. Different porous coatings for extracortical fixation. AB - The extent of extracortical bone-bridging and ingrowth into porous-coated prostheses for the stabilization of segmental defects was studied in a canine model. Initial fixation of the implant was achieved using bone cement. Autogenous bone grafts were applied over the porous-coated segmental portion of the prosthesis to stimulate the ingrowth and formation of bone. At twelve weeks, bone bridging and ingrowth occurred uniformly in both the titanium fibermesh and the cobalt-chromium-molybdenum beaded prostheses. Maximum formation of osseous tissue over the implants occurred at two to four weeks. More bone formed in the posterior aspect of the prosthesis. At twelve weeks, 26 per cent of the porous space of the titanium fibermesh prosthesis and 47 per cent of the porous space of the cobalt-chromium-molybdenum beaded prosthesis were filled with bone. The torsional strength and stiffness of the prosthetic midsection that contained a conical coupling joint were increased significantly due to bone-bridging and ingrowth. The cortical bone that was apposed to the segmental prosthesis showed an increase in porosity. The use of bone cement did not appear to impede new-bone formation extracortically. The initial stability of the implant and the application of sufficient autogenous bone grafts are two important factors that contribute to the ultimate stable fixation of an implant by extracortical bone formation. PMID- 3343261 TI - Chiari pelvic osteotomy in children and young adults. AB - We conducted a follow-up study of twenty-four patients who had been treated with a Chiari osteotomy at the Alfred I. duPont Institute between 1966 and 1981. The length of follow-up ranged from three to twenty years, and the age at operation ranged from ten to twenty-three years. The indication for the operation was either painful dysplasia or gross instability of the hip. Twelve patients had had congenital dislocation of the hip; six, poliomyelitis; three, cerebral palsy; and three had had another disorder. A good or excellent result was obtained in twenty one of the twenty-four patients. Preoperative pain and antalgic gait were consistently improved. In twenty-one patients, the osteotomy had to be displaced more than 50 per cent to provide adequate coverage of the femoral head, and bone grafting was necessary at the site of the osteotomy to prevent problems with healing. PMID- 3343263 TI - Tears of the meniscus as revealed by magnetic resonance imaging. AB - Forty-four patients who were examined by magnetic resonance imaging and arthroscopy to detect tears of the meniscus of the knee were studied. Twenty eight patients (Group I) had had no previous operations on the knee. Sixteen patients (Group II) had had a previous operation on the knee that had been performed after a meniscal injury. In Group I, the percentage of correct diagnoses by magnetic resonance imaging was 45 per cent. If the false-negative results are excluded, the rate of accuracy was 65 per cent. Similarly poor results were found in Group II: a rate of accuracy of 49 per cent and, if we eliminate the false-negative results, the rate of accuracy was only 55 per cent. PMID- 3343262 TI - The accuracy of selective magnetic resonance imaging compared with the findings of arthroscopy of the knee. AB - The results of selective magnetic resonance imaging of the knee were compared with those of arthroscopy in a prospective series of fifty patients. A specifically designed protocol for imaging, producing T1 sagittal images interleaved at four millimeters while the patient's foot was in 20 degrees of external rotation, was utilized. This technique, called selective magnetic resonance imaging, yielded excellent visualization of the posterior cruciate ligament, medial meniscus, and lateral meniscus in all patients. However, in only 76 per cent of the patients was the anterior cruciate ligament well visualized. Compared with arthroscopy, the sensitivity, specificity, and accuracy of selective magnetic resonance imaging were, respectively, 95.8, 100, and 98 per cent for tears of the medial meniscus; 66.7, 95.1, and 90 per cent for tears of the lateral meniscus; undefined, 100, and 100 per cent for tears of the posterior cruciate ligament; and 100, 96.9, and 97.3 per cent for tears of the anterior cruciate ligament, when that ligament was well visualized. Our selective sequence can be performed in fifteen minutes at a cost that is comparable with that of arthrography. It is totally non-invasive and requires no exposure to ionizing radiation. Selective magnetic resonance imaging can be a safe and valuable adjunct to the clinical evaluation of the knee and an aid to efficient preoperative planning. PMID- 3343264 TI - Transcutaneous oxygen tension as a predictor of success after an amputation. AB - We measured local transcutaneous oxygen tension at the foot and proximal and distal to the knee in 162 patients who then had 206 amputations. When the values for oxygen tension at the foot and distal to the knee were compared with the success or failure of healing after an amputation of the foot or distal to the knee, respectively, a clearly increasing probability of failure was correlated with decreasing transcutaneous oxygen tension. However, even at a tension of zero the probability of failure was not 100 per cent. The results were similar for diabetic and non-diabetic patients. Preoperative values for transcutaneous oxygen tension were a much more consistent predictor of success or failure of healing after an amputation of the foot or distal to the knee than were measurements of systolic blood pressure at the ankle, but neither was predictive of the outcome after an above-the-knee amputation. PMID- 3343265 TI - Anterior approach to the knee with osteotomy of the tibial tubercle for bicondylar tibial fractures. AB - Eight patients--six who had a bicondylar fracture of the tibia and two who had a complex fracture-dislocation--were treated by open reduction and internal fixation that was achieved through an anterior approach to the knee. The approach included elevation of the tibial tubercle, proximal retraction of the extensor mechanism (patellar tendon, retropatellar fat pad, and patella), and transection and detachment of the anterior horn of one or both menisci. The extent of the approach depended on the specific need for exposure. The quality of reduction was better and the rate of complications was lower, compared with conventional approaches. The main advantage of this approach is that the tibial plateau and the intercondylar notch are exposed clearly and completely; this is a prerequisite for the rapid reconstruction of the joint surface and, in some patients, for the reattachment or primary suture of the cruciate ligaments. I recommend the anterior approach with osteotomy of the tibial tubercle in the treatment of patients who have a severe displaced bicondylar fracture of the proximal end of the tibia. PMID- 3343266 TI - Dynamic electromyographic analysis of the throwing shoulder with glenohumeral instability. AB - Fifteen male athletes who were skilled in throwing and who had chronic anterior instability of the shoulder (Group 1) were evaluated by dynamic intramuscular electromyography while pitching a baseball. Indwelling wire electrodes recorded the levels of activity in the biceps, middle deltoid, supraspinatus, infraspinatus, pectoralis major, subscapularis, latissimus dorsi, and serratus anterior throughout the entire pitching sequence. These signals were synchronized electronically with records of the pitch that were made using high-speed photography. The pitch was divided into five phases: wind-up, early cocking, late cocking, acceleration, and follow-through. The results were compared with previous identical studies of twelve healthy, uninjured male athletes who were skilled in throwing (Group 2). Activity increased mildly in the biceps and supraspinatus in Group 1 as compared with Group 2. Similar patterns of activity were demonstrated in the deltoid. In Group 1 the infraspinatus had increased activity during early cocking and follow-through but had decreased activity during late cocking. The pectoralis major, subscapularis, latissimus dorsi, and serratus anterior in Group 1 all were shown to have markedly decreased activity. The study revealed a difference between Groups 1 and 2 in all of the muscles of the shoulder that were tested with the exception of the deltoid. The mildly increased activity levels of the biceps and supraspinatus that were found in Group 1 may compensate for anterior laxity. The marked reduction in activity in the pectoralis major, subscapularis, and latissimus dorsi added to the anterior instability by decreasing the normal internal-rotation force that is needed during the phases of late cocking and acceleration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343267 TI - Normal and abnormal mechanics of the glenohumeral joint in the horizontal plane. AB - This study was performed to evaluate the relationship of the humeral head to the scapula in the horizontal plane of motion and to describe in detail a method of obtaining and interpreting modified axillary roentgenograms. Twenty normal subjects and twelve patients who had anterior instability of the shoulder were evaluated with this technique. In the control group, the humeral head was centered in the glenoid cavity throughout the horizontal plane of motion except when the arm was in maximum extension and external rotation. In this position, the cocked stage of the throwing motion, the center of the humeral head rested approximately four millimeters posterior to the center of the glenoid cavity. When the arm was flexed or rotated from this cocked position, the humeral head glided anteriorly, producing a shearing stress on the articular surface of the glenoid and labrum. In seven of the twelve patients who had anterior instability, abnormal mechanics were observed: anterior translation of the humeral head occurred. This indicates a significant disruption of the structures responsible for containing the humeral head within the glenoid fossa. PMID- 3343268 TI - Traumatic posterior fracture-dislocation of the hip with fracture of the femoral head or neck, or both. AB - To determine the prognosis and best treatment for patients who have a posterior dislocation of the hip associated with a fracture of the femoral head or neck (Grade IV, according to the classification of Stewart and Milford), we surveyed the records of 201 patients who had been treated for 203 posterior dislocations from 1958 to 1985 and selected the cases of 19 patients (19 posterior fracture dislocations of the hip) for further review. Each of the injuries had resulted from a motor-vehicle accident. Thirteen patients had had a posterior dislocation with an associated fracture of the femoral head located either caudad or cephalad to the fovea centralis (Pipkin Type-I or Type-II injury), one had had a posterior dislocation with associated fractures of the femoral head and neck (Pipkin Type III), two had had a posterior dislocation with associated fractures of the femoral head and the acetabular rim (Pipkin Type IV), and three had had a fracture-dislocation that we could not categorize according to the Pipkin classification. Twelve patients had been treated by closed reduction for a Type-I or Type-II injury; one, by open reduction after an unsuccessful closed reduction for a Type-I injury; one, by primary total hip replacement for a Type-III injury; and three, by open reduction with screw fixation of the acetabular fracture and removal of the fragment of the head for two Type-IV injuries and one unclassified injury. An additional two patients had had both a fracture of the femoral neck and a dislocation; one hip was treated primarily with a Moore prosthesis and the other was left unreduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343269 TI - Intraoperative and postoperative subtrochanteric fracture of the femur associated with removal of the Zickel nail. AB - Twelve patients, whose ages ranged from twenty-one to sixty-eight years (mean, 32.6 years) and in whom a Zickel nail had been used to treat an acute traumatic subtrochanteric fracture of the femur, had fourteen subtrochanteric refractures that were associated with removal of the nail. The refracture was always different from the original fracture in type and site (being located an average of 4.3 centimeters distal to the lesser trochanter). Five of the refractures were recognized intraoperatively at the time of removal of the nail. Because of this potential complication, we believe that the Zickel nail should not be used in the treatment of subtrochanteric fractures of the femur in young patients. PMID- 3343270 TI - Simple dislocation of the elbow in the adult. Results after closed treatment. AB - The long-term results after treatment of simple dislocation of the elbow in fifty two adults were evaluated with regard to limitation of motion, pain, instability, and residual neurovascular deficit. All patients were treated with traditional closed reduction, but the duration of immobilization before commencement of active motion varied. Goniometric, photographic, and radiographic data were compiled for these patients, who had an average follow-up of 34.4 months. Despite the generally favorable prognosis for this injury, 60 per cent of the patients reported some symptoms on follow-up. A flexion contracture of more than 30 degrees was documented in 15 per cent of the patients; residual pain, in 45 per cent; and pain on valgus stress, in 35 per cent. Prolonged immobilization after injury was strongly associated with an unsatisfactory result. The longer the immobilization had been, the larger the flexion contracture (p less than 0.001) and the more severe the symptoms of pain were. The results indicate that early active motion is the key factor in rehabilitation of the elbow after a dislocation. PMID- 3343271 TI - Force transmission through the radial head. AB - A technique has been developed to study the transmission of axial force across the radiohumeral joint during simulated active motion of the elbow. Variations in the line of action and in the amount of muscle load, as well as in rotation of the forearm during flexion and extension of the elbow, were assessed. Consistent patterns of force transmission were demonstrated in the three specimens that were studied. The greatest force transmission occurred between zero and 30 degrees of flexion, and it consistently decreased with increased flexion. Force transmission was consistently greater in magnitude when the forearm was in pronation than when it was in supination. The varus-valgus pivot point with the elbow extended was established to closely approximate the line of action of the brachial muscle, which crosses near the center of the lateral portion of the trochlea. PMID- 3343272 TI - Villous lipomatous proliferation of the synovial membrane (lipoma arborescens). AB - The cases of five patients (7 knees) who had villous lipomatous proliferation of the synovial tissue (lipoma arborescens) are reported. The longest duration of symptoms was thirty years. Six of the seven knees were treated by synovectomy. The length of follow-up ranged from two to eleven years, and six knees were followed for five years or more. The patients who were treated by synovectomy had complete healing of the synovial lesion, but the osteoarthritis tended to progress, especially in patients who had long-standing symptoms. Because of the clinical, macroscopic, and microscopic features of this rare disease, we suggest discarding the name lipoma arborescens, which implies that the lesion is a neoplasm, and using the more descriptive term of villous lipomatous proliferation of the synovial membrane. PMID- 3343273 TI - Dimensional changes of the feet in pregnancy. AB - Serial measurements of the volume, length, and width of the feet of seventeen pregnant women were made at, or close to, the thirteenth and thirty-fifth weeks of pregnancy and eight weeks postpartum. The same measurements were made twice on a control group of sixteen nulliparous women at intervals that ranged from sixteen to twenty weeks. There was no change in the length or width of the feet in either group. The mean volume of the feet increased 57.2 milliliters between early and late pregnancy (p less than 0.001) and decreased by only 8.42 milliliters between late pregnancy and eight weeks postpartum. These changes were attributed to retention of fluid or to an increase in soft tissue and not to stretching or relaxation of the ligaments. PMID- 3343274 TI - Orthopaedic injuries in children associated with the use of off-road vehicles. AB - Two hundred and thirty-three children who had musculoskeletal injuries related to the use of off-road vehicles were admitted to acute-care hospitals in the two largest urban centers in Manitoba between April 1979 and August 1986. There were 190 boys and forty-three girls, and the ages ranged from two to seventeen years. Ninety-three accidents involved the use of a minibike or dirtbike; seventy-two, a snowmobile; fifty-nine, a three-wheeled all-terrain vehicle; and nine, a four wheeled all-terrain vehicle. The injuries in 73 per cent of the children occurred in a rural setting. The use of alcohol or a drug was recorded for only three children. Loss of control of the vehicle led to the majority of injuries. There were 352 fractures of an extremity or the spine and fifty-one major soft-tissue injuries of the musculoskeletal system; 186 (53 per cent) of the fractures were displaced, 107 (46 per cent) of the patients had more than one fracture, and thirty-four (10 per cent) of the fractures were open. There were sixty growth plate injuries. A total of 186 associated injuries were present in ninety-one patients. In a separate review of the records of the Chief Medical Examiner, it was noted that twenty-one fatal accidents that were related to the use of off road vehicles occurred in the Province of Manitoba during the same period of time. PMID- 3343275 TI - Knee arthrodesis with a tension-band plate. AB - Twenty-six patients had an arthrodesis of the knee using a single anterior, broad, contoured dynamic-compression plate and screws that were applied as a tension band. Bone grafts were not used. No external immobilization was required, and immediate partial weight-bearing was encouraged. The minimum follow-up period was two years, and solid osseous union occurred in each patient. When last seen, all patients were free of pain and could walk without external support. The desired alignment was achieved in each patient, and no complications that were related to this method occurred. Tension-band plating, in our opinion, represents the best method of arthrodesis of the knee that is currently available. PMID- 3343276 TI - Separation of the symphysis pubis in association with childbearing. A case report. PMID- 3343277 TI - Osteonecrosis of the acetabulum following radiation therapy. A report of two cases. PMID- 3343278 TI - Multiple non-ossifying fibromas. A case report. PMID- 3343280 TI - The type-IIIC tibial fracture. Salvage or amputation. PMID- 3343281 TI - Postoperative ulnar-nerve palsy. Are there predisposing factors? PMID- 3343279 TI - Recurrent fractures of the humerus in a baseball pitcher. A case report. PMID- 3343282 TI - Proceedings: 19th National Cancer Congress of the German Cancer Society. February 28-March 5, 1988, Frankfurt/Main, Federal Republic of Germany. Abstracts. PMID- 3343283 TI - Small joint injuries of the hand. Dynamic and functional implications. AB - An injury to one of the small joints of the hand may have a major impact on hand function and thus have major implications for career and avocation. Proper treatment demands a knowledge of hand anatomy and dynamic function. Proper primary treatment usually yields better results than attempted late reconstruction; however, even with the best of primary care, long-range significant disability may result. PMID- 3343284 TI - Small joint injuries. PMID- 3343285 TI - Principles and guidelines in hand therapy and rehabilitation during recovery from small joint injuries. AB - A successful return to functional use following joint injuries of the hand can be obtained by proper evaluation and treatment. Knowledge of injury, proper splinting, and treatment of modalities used are of utmost importance. An open channel of communication with the patient and hand surgeon will assist in establishing realistic goals. PMID- 3343286 TI - Troublesome shaft fractures of the proximal phalanx. Early treatment to avoid late problems at the metacarpophalangeal and proximal phalangeal joints. AB - Although any fracture of the proximal phalanx can potentially disrupt finger MCP and/or PIP motion, appropriate consideration based on sound principles of biomechanics and biology of healing will delineate the options available. Applying the risk/benefit associated with any particular mode of treatment is more challenging. Perhaps the most difficult thing is to anticipate and recognize failure of a treatment mode sufficiently early and then to act concisely to rectify the situation. The physician and patient must recognize what goal is realistic for each patient's injury. This encompasses the patient factors as outlined, as well as a clear awareness in the surgeon's mind of his or her technical limitations and expertise. Final function and range of motion of the MCP and PIP joints will depend not only on bony union in good position, but on restoration of the gliding function of the flexor and extensor tendons that are contiguous to the fracture site. PMID- 3343288 TI - Identification and characterization of tyrosine kinase activity associated with mitochondrial outer membrane in sarcoma 180 cells. AB - Tyrosine protein kinase activity has been detected in the mitochondrial fraction purified from sarcoma 180 tumor cells. Following hypotonic disruption of mitochondria, tyrosine kinase activity appeared to cosediment with monamine oxidase, marker enzyme of mitochondrial outer membrane; meanwhile, serine and threonine kinases were found to be associated with the inner membrane and matrix of mitochondria. Mitochondrial tyrosine kinase(s) showed thermosensitivity and Mn2+ dependence, useful properties for its characterization and separation from tyrosine kinases associated with other particulate fraction and from serine and threonine kinases associated with mitochondria. Following in vitro incubation of mitochondria with labelled ATP as substrate and analysis by PAGE, a complex pattern of phosphotyrosine containing proteins with a major band of 50-55 kilodaltons resulted. PMID- 3343287 TI - Phosphatidylinositol cycle and its possible involvement in the regulation of cytoskeleton-membrane interactions. AB - Receptor-mediated activation of many cells, including blood platelets, leads to changes at the cytoplasmic side of the membrane. In platelets, phospholipases, such as phospholipase C and phospholipase A2, have been shown to become activated. From phospholipids they generate the second messengers diacylglycerol and inositol phosphate(s) and fatty acids, respectively. At the same time, actin polymerization and reorganization of actin filaments into bundles and networks occurs. Here, the association of lipids, radiolabeled either with saturated (palmitic acid) or unsaturated (arachidonic acid) fatty acids, with the cytoskeletons of resting and activated human blood platelets was studied. The relative binding of lipid components to the cytoskeleton of activated platelets labeled with palmitic acid is six times higher than that of platelets labeled with arachidonic acid. Analysis of lipids associated with isolated cytoskeletons of resting and activated platelets (labeled with palmitic acid) showed a 30-fold increase in the binding of labeled lipids to the cytoskeletal structures during activation. Both diacylglycerol and fatty acids were found to be associated with the cytoskeleton of activated platelets. Gel filtration, chromatofocusing, and immunoprecipitation studies demonstrated tight binding of these lipids to alpha actinin. alpha-Actinin is one of the proteins that rapidly becomes associated with the cytoskeleton during platelet aggregation; it is also one of the molecules proposed to act as an actin-membrane linker. The results reported indicate a possible participation of alpha-actinin, fatty acids, and the phosphoinositide-derived second messenger diacylglycerol in the regulation of cytoskeleton-membrane interactions. Together with the results of others they suggest a possible involvement of the phosphatidylinositol cycle in the assembly of actin filaments and their anchoring to membranes. PMID- 3343289 TI - Differences in mortality rate between abrupt and progressive carotid ligation in the gerbil: role of endogenous angiotensin II. AB - Studies have shown that in comparison to rapid occlusion of a vessel, gradual occlusion produces less severe tissue ischemia due to a more effective development of collateral circulation. As other studies have shown that collateral circulation can be enhanced by stimulation of the endogenous renin angiotensin II system, it was hypothesized that this system is involved in the mechanism of protection against ischemia that obtains during gradual vascular occlusion. To test this hypothesis, mortality rates were evaluated in gerbils subjected to gradual vascular occlusion by means of progressive carotid ligation while simultaneously infused with inhibitors of the renin-angiotensin II cascade- enalaprilat or saralasin. Groups of animals with either abrupt or progressive carotid ligation infused with saline served as controls. Results showed that (1) in saline-infused animals, there was a significant decrease in the mortality rate of progressive-ligated animals when compared to abrupt-ligated animals, and (2) administration of either enalaprilat or saralasin to progressive-ligated animals resulted in mortality rates that were indistinguishable from those of saline infused abrupt-ligated animals. These results suggest that the endogenous renin angiotensin system is indeed involved in an adaptive mechanism that occurs during progressive ligation of the carotid artery, and more specifically, that the relatively benign effect of progressive carotid ligation may be due to the action of angiotensin II to stimulate the development of collateral circulation and reduce the severity of focal brain ischemia. PMID- 3343291 TI - O2 dependence of in vivo brain cytochrome redox responses and energy metabolism in bloodless rats. AB - Oxygen-dependent changes in brain cytochrome redox state and cerebrocortical energy metabolism were evaluated in fluorocarbon-circulated rats at hematocrits of less than 1%. Redox levels of three respiratory chain cytochrome complexes, b, c, and a,a3 (cytochrome c oxidase), were continuously measured directly through the intact skulls of animals using reflectance spectrophotometry. The in vivo redox status of cytochromes at different FiO2 was directly compared with in vitro measured changes in cortical metabolites known to reflect energy production, i.e., glucose, pyruvate, lactate, phosphocreatine (PCr), ADP, and ATP. Lowering the FiO2 to less than 1.0 caused the cytochromes to become increasingly more reduced. This was associated with increased tissue accumulation of pyruvate and lactate and a concomitant increase in the lactate/pyruvate (L/P) ratio. At FiO2 = 0.6, cytochromes b, c, and a,a3 were 57, 53, and 46% reduced, respectively. There was no apparent cerebral energy deficit since changes in cortical PCr, ADP, and ATP concentrations were not statistically significant. Bloodless animals did not survive below FiO2 = 0.5. At this FiO2, the inability of the animals to sustain arterial pressure correlated (r = 0.87) with depletion of PCr and further increases in the L/P ratio (r = 0.66). Yet, the cortical ATP content was reduced by only 9% of control value. These data provide direct evidence that fluorocarbon emulsion (FC-43) sustains brain oxygenation and energy metabolism at high partial pressures of molecular O2. At lower FiO2, however, mitochondrial O2 uptake becomes limited as a function of decreasing perfusion pressure. PMID- 3343290 TI - Potassium ion homeostasis and mitochondrial redox activity in brain: relative changes as indicators of hypoxia. AB - This study was directed at relating ion transport and mitochondrial redox activity during hypoxia, as a step toward definition of brain oxygen sufficiency. To accomplish this, extracellular potassium ion activity (K+o) was recorded by ion-selective microelectrodes while reduction/oxidation (redox) ratios of cytochrome oxidase (cytochrome a,a3) were monitored by reflection spectrophotometry in cerebral cortex of rats anesthetized with pentobarbital. In normoxia, neuronal activation by direct cortical stimulation produced transient oxidation of cytochrome a,a3 and elevation of K+o. Moderate hypoxia (PaO2 above 50 mm Hg) resulted in reduction of cytochrome a,a3 but only slight elevation of K+o. At this level of hypoxia, cytochrome a,a3 continued to respond to neuronal activation with transient shifts toward oxidation and rates of K+o reaccumulation were unchanged from control. When PaO2 was further decreased below a critical threshold, stimulus-provoked oxidative responses of mitochondrial reactants were replaced by shifts toward reduction, but rates of reaccumulation of K+, spilled into the extracellular space by neuronal activation, remained unchanged. Only during severe hypoxia (PaO2 less than 20 mm Hg) was it possible in some animals to record a slowing in the reaccumulation of K+o without provocation of spreading cortical depression. These data indicate that ion transport activity in cerebral cortex is more refractory to hypoxia than is mitochondrial redox functioning. They suggest an in vivo parallel to the "cushioning" effect of mitochondria in vitro, in which oxygen consumption remains constant despite fluctuations in oxygenation and redox ratios, and also that there may be a greater anaerobic capacity to provide energy for ion transport in mammalian brain than has previously been appreciated. PMID- 3343292 TI - Effects of nifedipine and felodipine on adenosine and inosine release from the hypoxemic rat cerebral cortex. AB - The cerebral cortical cup technique has been used to study the effects of nifedipine and felodipine on adenosine and inosine release from the rat brain. After basal and hypoxia (8% 02)-evoked control levels of purine release had been established, these 1,4-dihydropyridine calcium antagonists were administered intraperitoneally (1 mg/kg). Both agents depressed basal levels of purine efflux and suppressed the hypoxia-evoked release of adenosine and inosine. An inhibition of the transporter that mediates purine efflux from brain cells is likely to account for the suppression of release from the cerebral cortex. A reduced release of adenosine into the interstitial space also explains the ability of both agents to block the increase in CBF evoked by hypoxic challenges. PMID- 3343294 TI - Effects of lactic acid infusions and pH on cerebral blood flow and metabolism. AB - To determine the effects of lactic acidemia versus lactate on CBF, we infused lactic acid, either buffered with NaOH (L + NaOH) or with added NaCl (L + NaCl), to attain similar osmolalities in 18 piglets. CBF (microsphere technique), pH, blood gases, plasma osmolality, and cerebral arteriovenous differences of O2 content and lactic acid concentrations were measured prior to, at 30 min of a lactic acid infusion, and 15 and 90 min after completion of the infusion. Control arterial pH was comparable between groups (7.50 +/- 0.02 vs. 7.49 +/- 0.02, X +/- SE); during and following L + NaCl and L + NaOH, values were (p less than 0.05) 7.09 +/- 0.03, 7.35 +/- 0.02, and 7.46 +/- 0.02 vs. 7.58 +/- 0.03, 7.61 +/- 0.01, and 7.57 +/- 0.03, respectively. PaCO2 remained unchanged and osmolality rose by 15% in both groups during infusions and persisted throughout the study period. For L + NaCl piglets, CBF (ml/min.100 g) rose from 136 +/- 15 to 198 +/- 26 (p less than 0.05) at 30 min of infusion and remained elevated at 201 +/- 25 and 207 +/- 28 at 15 and 90 min following the infusion, respectively. Similarly, for L + NaOH piglets, CBF rose from 130 +/- 25 to 196 +/- 31 (p less than 0.05) with the infusion and was 174 +/- 17 and 166 +/- 21 at 15 and 90 min afterward, respectively. Although lactic acid infusion increases CBF, the associated metabolic acidemia is not responsible for changes in CBF. PMID- 3343293 TI - Hyperglycemia increases infarct size in collaterally perfused but not end arterial vascular territories. AB - Hyperglycemia exacerbates neuronal injury in the setting of reversible brain ischemia, but its effect on focal thrombotic infarction has been less extensively characterized. We investigated this problem in two rat models of focal vascular occlusion. In Model I, the right middle cerebral artery (MCA) was exposed via a subtemporal craniotomy in halothane- and nitrous oxide-anesthetized Wistar rats and was occluded photochemically by irradiation with an argon ion laser following the intravenous administration of the photosensitizing dye rose bengal. Permanent MCA occlusion was combined with temporary bilateral common carotid artery ligation. In Model II, similarly anesthetized Sprague-Dawley rats were subjected to permanent photochemical occlusion of the right MCA without common carotid occlusion. In both models, rats were food deprived for 24 h and were administered varying amounts of 50% dextrose (or saline) 15 min prior to vascular occlusion to produce a spectrum of plasma glucose values, ranging from 5 to 44 mumol/ml. Brains were examined histologically 7 days following vascular occlusion, and computer-assisted planimetry was used to compute infarct volumes. In Model I, the volume of neocortical infarction ranged from 30.3 to 108.4 mm3 and exhibited a strong linear correlation with increasing preischemic plasma glucose values (r = 0.70). In contrast, the size of the smaller striatal infarct in this model was not correlated with plasma glucose level. In Model II, there was a prominent striatal infarct, ranging in volume from 14.4 to 96.4 mm3, while neocortical infarction occurred inconstantly. As in Model I, striatal infarct volume in Model II showed no correlation with plasma glucose level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343295 TI - Brain oxidative metabolism of the newborn dog: correlation between 31P NMR spectroscopy and pyridine nucleotide redox state. AB - The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pi levels measured by 31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1-21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1-2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pi values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343296 TI - Computer-regulated constant pressure ischemia in the rat: the animal model. AB - A system permitting computer control of partial ischemia in the normotensive rat brain was developed. Right carotid cannulation and bilateral subclavian artery occlusion made the input of blood to the brain dependent solely on left carotid artery flow. Perfusion pressure was controlled by partial compression of this artery with a balloon. The system can produce a range of partial ischemic states maintaining perfusion pressures from 4 to 20 mm Hg. The adequacy of the servo control system was evaluated in greater detail at requested perfusion pressures of 7 and 12 mm Hg in 14 male Sprague-Dawley rats (300-450 g). Experimentally obtained cerebral perfusion pressures of 6.84 (SD = 0.25, n = 7) and 11.72 (SD = 0.89, n = 7) mm Hg, respectively, demonstrate the efficacy of the system. CBFs were concurrently measured at four separate bilaterally symmetric anatomic sites (cortex, hippocampus, thalamus, and substantia nigra). Significant intra- and interhemispheric differences were found to exist, with regional flows monitored ipsilaterally to the carotid balloon exceeding those of the opposite hemisphere. In summary, this acute model of cerebral ischemia permits control of perfusion pressure over the entire critical partial ischemic range. PMID- 3343297 TI - Tracer 2-deoxyglucose kinetics in brain regions of rats given kainic acid. AB - The initial distribution of tracer amounts of 2-deoxyglucose between plasma and brain tissue, relative to native glucose, and the rate of accumulation of 2 deoxyglucose-6-phosphate were determined in brain regions of rats given kainic acid intravenously. Regional plasma flow was measured in a comparable group of animals. A previously described compartmental model was used to obtain estimates of rates of glucose transport and of glucose phosphorylation. Both rates were significantly increased in entorhinal cortex, hippocampus, amygdala, and septal nucleus. From measured brain tissue and plasma glucose concentrations, glucose fluxes were also calculated in terms of either irreversible or reversible Michaelis-Menten kinetics. In all brain regions of control rats and in six of the ten regions studied in rats given kainic acid, rates of glucose transport calculated in terms of the Michaelis-Menten models were consistent with those estimated by the tracer 2-deoxyglucose procedure. However, in the four regions in which glucose metabolism was stimulated, rates of glucose transport calculated from the behaviour of tracer 2-deoxyglucose were considerably higher than rates calculated from measured concentrations of glucose in plasma and brain tissue using Michaelis-Menten models. The possibility is considered that in those regions that are metabolically stimulated by kainate, there is an increasing asymmetry between the luminal and abluminal membranes of the capillary endothelium in the permeability to glucose and its analogs. An alternative proposal is that in the model used to analyse the tracer 2-deoxyglucose data, the assumption of a rapid mixing of tracer throughout the endogenous pool of tissue glucose prior to phosphorylation becomes invalid. The discrepancies between tracer and native glucose in these particular regions of rats given kainate are consistent with an apparent metabolic compartmentation. The influence of kainate on plasma flow was found to differ regionally, with flow in entorhinal cortex, hippocampus, and amygdala being unchanged. There is some evidence for increased rates of glycolysis relative to oxidative metabolism in these regions. PMID- 3343298 TI - Brain enzyme levels in CSF after cardiac arrest and resuscitation in dogs: markers of damage and predictors of outcome. AB - Levels of brain creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD) in CSF after cardiac arrest were studied in dog models. Ventricular fibrillation cardiac arrest lasting 10 min or asphyxiation cardiac arrest lasting 0-10 min was followed by cardiopulmonary resuscitation and 96-h intensive care. Outcome was scored as neurologic deficit (0% = normal, 100% = brain death) and overall performance category (1 = normal, 5 = death). Both measures correlated with EEG return time after asphyxiation cardiac arrest, but not after ventricular fibrillation cardiac arrest. Peak activity of enzymes in CSF at 48-72 h post arrest correlated with outcome, and CK was the best predictor. Brain histopathologic damage score at autopsy 96 h post arrest correlated with CK level in CSF (r = 0.79, n = 39) and neurologic deficit (r = 0.70, n = 50). Ischemic neuronal changes occurred after ventricular fibrillation cardiac arrest of 10 min, and neuronal changes plus microinfarcts occurred after asphyxiation cardiac arrest of 1.5-10 min. Brain enzymes were decreased at 6 h post arrest in regions with worst histologic damage (gray matter of neocortex, hippocampus, caudate nucleus, cerebellum). Brain CK decreased further, ASAT remained low, and LD increased at 72 h after arrest. The temporal changes in CK level paralleled the temporal ischemic neuronal changes in the brain, and time to peak activity was unaffected by the severity of the ischemic insult. Peak activity of individual enzymes in CSF was determined predominantly by the brain concentration, but was also influenced by rate of decomposition. This "chemical brain biopsy method" represents a useful adjunctive tool to predict permanent, severe brain damage during comatose states after cardiac arrest and resuscitation. PMID- 3343299 TI - 19F imaging of cerebral blood oxygenation in experimental middle cerebral artery occlusion: preliminary results. AB - Fluorine (19F) nuclear magnetic resonance may be used to image cerebral perfusion in cats receiving perfluorocarbon blood substitutes. 19F relaxation times in these blood substitutes are dependent on oxygen tension (PO2) and may be used to calculate and spatially map cerebrovascular PO2 values in vivo. We have applied this noninvasive method to experimental middle cerebral artery (MCA) occlusion. Following MCA occlusion a perfusion defect is evident in the sylvian region, followed by the appearance of collaterals. Signal from the ipsilateral rete mirabilis is increased. Calculated cortical vascular PO2 values indicate a relative reduction in oxygenation in the ischaemic hemisphere. PO2 maps show a perfused hypoxaemic zone adjacent to the perfusion defect. These changes are partly reversed with reperfusion. PMID- 3343300 TI - Quantitative evaluation of vascular permeability in the gerbil brain after transient ischemia using Evans blue fluorescence. AB - Mongolian gerbils were used to evaluate brain edema during restoration of flow following bilateral carotid occlusion for 1 h. We have modified the method for fluorometric measurement of Evans blue to monitor vascular protein leakage (vasogenic edema). The extraction of extravasated Evans blue was performed by homogenizing the whole brain in 50% trichloroacetic acid. The supernatant was diluted fourfold with ethanol and the Evans blue fluorescence was measured. The tissue blank was negligible. Evans blue content of the plasma was similarly determined and the ratio of tissue to plasma Evans blue content was calculated. Furthermore, Evans blue fluorescence was used for microscopic investigation. It is suggested that Evans blue fluorescence can be applied for quantification of protein leakage with much more sensitivity and accuracy than the colorimetric absorbance method, as well as for tissue localization of protein leakage. PMID- 3343301 TI - Rapid MIC testing with the sensititre autoreader. AB - Automated microdilution MIC results, obtained with the Autoreader (Sensititre, Inc., Salem, N.H.) following 5 h of incubation, were compared with manually read, concurrent control MICs following 18 h of incubation in a three-laboratory comparative study. A total of 704 members of the family Enterobacteriaceae or similar gram-negative organisms were tested against 17 antimicrobial agents. Autoreader MICs were within 1 doubling dilution of control values in 92.9% of instances. Discrepancies of +/- 2 doubling dilutions and +/- 3 or greater doubling dilutions were noted in 4.5 and 2.6%, respectively, of the 7,687 drug organism combinations analyzed. The majority of errors occurred when beta-lactam antimicrobial agents were tested with a variety of different species. MICs at 5 h, when Pseudomonas aeruginosa was used, were possible in only half the isolates tested and yielded data on only a limited number of drugs in the remaining instances. Excluding results obtained with penicillin and ampicillin, which were uniformly poor, Staphylococcus aureus Autoreader values were within +/- 1 doubling dilution of control values in 93.6% of instances, 5.4% varied by +/- 2 dilutions, and only 1% of test values by +/- 3 or more dilutions from control values for 82 isolates tested against nine antimicrobial agents. Of eight additional S. aureus isolates tested that were resistant to methicillin, only one was read correctly by the Autoreader, with results on the remaining seven appearing as either insufficient growth or as total resistance to all drugs tested. Interlaboratory reproducibility was excellent for selected isolates of S. aureus and gram-negative bacilli. The accuracy of the Sensititre Autoreader MIC results was comparable to that of other same-day quantitative systems for members of the family Enterobacteriaceae and S. aureus, while the economic and procedural advantages of the broth microdilution method was maintained. PMID- 3343302 TI - Characterization of an unclassified microaerophilic bacterium associated with gastroenteritis. AB - Four isolates of an unclassified microaerophilic bacterium resembling Campylobacter species were characterized by growth requirements, microscopic examination, biochemical characteristics, antimicrobial susceptibility tests, and protein profile analysis. The unclassified isolates were differentiated from Campylobacter jejuni, Campylobacter coli, Campylobacter fetus subsp. fetus, Campylobacter laridis, Campylobacter pylori, and an ovine isolate. The bacterium was fusiform shaped with a corrugated surface due to the presence of periplasmic fibers and had multiple bipolar flagella. Biochemically, the bacterium was separated from the Campylobacter controls by its negative catalase reaction, negative nitrate reduction, and no growth in 1% glycine. It was also resistant to ampicillin. Protein profile analysis demonstrated nine major protein bands present in the unclassified isolates that were absent in the Campylobacter controls. The bacterium also differed from the ovine isolate by its negative catalase reaction, rapid urea hydrolysis, and susceptibility to clindamycin, erythromycin, and tetracycline. Our results showed that the unclassified bacterium was distinct from the recognized Campylobacter species. PMID- 3343303 TI - Antibodies to cysts of Giardia lamblia in primary giardiasis and in the absence of giardiasis. AB - The significance of serum antibodies binding to cysts of Giardia lamblia was evaluated by indirect immunofluorescence. Titers of 10 or higher were found in 85.6% of adults, who had probably never had giardiasis. Titers in 118 adults (geometric mean, 29.9) were higher than in 35 children (16.4), and titers in women (42.3) were higher than in men (20.0). Titers in 150 patients with primary giardiasis (80.4) were higher than in control adults, but overlapping precluded serological diagnosis. Titers increased with the duration of infection. Female patients had higher titers (100.5) than did males (66.1), but men who had been infected longer than 45 days had high titers (132). Titers in second serum samples taken from 26 patients 2 weeks to 3 months after successful nitroimidazole treatment (58.1) were lower than before treatment (151.7) but higher than in 118 controls. We conclude that most people have antibodies which cross-react with G. lamblia but which are induced by other immunogens and that primary giardiasis induces protracted systemic antibody responses. PMID- 3343304 TI - Criteria for disk susceptibility tests and quality control guidelines for the cefoperazone-sulbactam combination. AB - For in vitro susceptibility tests with cefoperazone and sulbactam (a beta lactamase inhibitor), 75/30-micrograms disks may be used with the interpretive zone size breakpoints that are currently used for 75-micrograms cefoperazone disks. For dilution tests, a 2:1 ratio of cefoperazone to sulbactam is recommended. For quality control purposes, MIC limits that are used to monitor cefoperazone tests were also applied to tests with the combination of drugs. For gram-negative control strains, zone size limits were calculated to be 1 mm smaller than those used for cefoperazone disks. To monitor the sulbactam portion of the combination, Acinetobacter calcoaceticus subsp. anitratus ATCC 43498 was selected; zones with 75/30-micrograms disks were 26 to 32 mm in diameter, and broth microdilution MICs ranged from 1.0/0.5 to 8.0/4.0 micrograms/ml. With cefoperazone alone, MICs for Acinetobacter calcoaceticus subsp. anitratus were 16 to 64 micrograms/ml and zones ranged from 14 to 18 mm in diameter. For anaerobic dilution tests, only Bacteroides thetaiotaomicron ATCC 29741 is recommended for cefoperazone-sulbactam; MICs ranged from 8.0/4.0 to 32/16 micrograms/ml. PMID- 3343305 TI - Survival of bacteria in Difco CultureSwab and Marion Culturette II transport systems. AB - The effects of the CultureSwab (Difco Laboratories, Detroit, Mich.) and Culturette II (Marion Scientific, Div. Marion Laboratories, Inc., Kansas City, Mo.) transport systems on the viability of 95 clinically significant bacteria were studied. Organisms included staphylococci (8 isolates), streptococci (22 isolates), Haemophilus spp. (16 isolates), members of the family Neisseriaceae (14 isolates), Bordetella spp. (5 isolates), members of the family Enterobacteriaceae (16 isolates) and pseudomonads (14 isolates). Viability counts with both methods usually dropped by greater than or equal to 90% after incubation at room temperature for periods ranging from 4 to 48 h, and statistically significant differences between the two methods were not observed. However, counts were generally higher with the Difco method, and this difference may be clinically important. PMID- 3343306 TI - Calcium requirement for syncytium formation in HEp-2 cells by respiratory syncytial virus. AB - Respiratory syncytial virus (RSV) grown in HEp-2 cells in the absence of calcium did not induce cell fusion and syncytium formation. Although the infected cells contained viral antigens, the cytopathic effect (giant cell formation) typical for RSV was not observed in calcium-free cultures. Infectious virus yield was also slightly reduced (less than a one log10 reduction) in the absence of calcium. An analysis of viral proteins synthesized in both the presence and the absence of calcium revealed that the amount of fusion protein (F1) in calcium free infected cultures was approximately one-third that in calcium-containing infected cultures. These results underscore the necessity of using calcium containing growth medium for cell culture isolation and diagnosis of RSV. PMID- 3343307 TI - Case report of an unclassified microaerophilic bacterium associated with gastroenteritis. AB - An unusual microaerophilic gram-negative bacterium was isolated from the stools of two individuals presenting with chronic diarrhea. This bacterium resembled Campylobacter species by colonial morphology and biochemical reactions. However, microscopic examination revealed a fusiform rod with a corrugated surface, rather than a spiral rod. This is the first reported isolation of this bacterium from humans. PMID- 3343308 TI - Quantitation of indirect sandwich enzyme-linked immunosorbent assay parameters. AB - The optimization of data from the indirect sandwich enzyme-linked immunosorbent assay has been commonly accomplished by linear regression analysis, even though the data are often essentially sigmoid. A new microcomputer software program (LISACRV) that uses a nonlinear regression statistical model to analyze the data from enzyme-linked immunosorbent assay titration experiments was developed. PMID- 3343309 TI - Fatty and mycolic acids of Mycobacterium malmoense. AB - The fatty acids and mycolic acids of 16 clinical isolates of Mycobacterium malmoense were studied by gas chromatography and thin-layer chromatography. All strains contained 2-methyleicosanoic and 2,4,6-trimethyltetracosanoic acids and alpha-, alpha'-, and keto-mycolic acids. The reported findings suggest that lipid analysis is a very useful approach in the species identification of M. malmoense. PMID- 3343311 TI - Analysis of antimicrobial susceptibility results using microcomputers. AB - A computer program has been developed on an IBM-PC-compatible microcomputer to analyze antimicrobial susceptibility results of large numbers of organisms tested against a variety of antimicrobial agents. For each species, the output includes the numbers, percentages, cumulative numbers, and cumulative percentages of organisms inhibited at different concentrations of each drug, the MICs for 50 and 90% of organisms tested, MIC ranges, and geometric mean MICs. The distributions of MICs are also plotted as histograms. The program was written in dBASE III command language, but a compiled version allows rapid program execution independently of the dBASE III package. PMID- 3343310 TI - Mesenteric lymphadenitis of swine caused by Rhodococcus sputi. AB - Rhodococcus sputi caused tuberculosislike lymphadenitis of mesenteric lymph nodes in swine. This is the first study reporting that R. sputi can be a pathogen in swine. PMID- 3343312 TI - Effects of amines and polyamines on turbidimetric and lysoplate assays for lysozyme. AB - The lysoplate and turbidimetric assays have often been used to measure lysozyme in biological fluids, such as blood and saliva. When the same purified lysozyme standard is used in both assays, results obtained with the lysoplate assay are much higher than those obtained for the same sample in the turbidimetric assay. It is likely, therefore, that other components in the biological fluid sample influence the expression of lysozyme activity in one or both assays to produce such divergent results. Certain amines or polyamines are found in various biological fluids and have the potential to influence the reactions in these two assay systems. It was the purpose of this study to incorporate selected amines and polyamines into purified lysozyme preparations and saliva or into the assay preparations to compare their effects on observed lysozyme activity between the two assay systems. Results showed that when the amine or polyamine was included in the purified sample, lysozyme activity was considerably greater than that of controls in the lysoplate assay, whereas a negligible effect was observed in the turbidimetric assay. If the amine or polyamine was incorporated into the assay preparation, results were more dramatic, with large increases in activity in the lysoplate assay and concomitant inhibition in the turbidimetric assay. Similar effects were observed in the assay of lysozyme in saliva, suggesting a potential mechanism by which the two assay systems produce markedly different results for the same sample. PMID- 3343313 TI - Prevalence of capsular polysaccharide types 5 and 8 among Staphylococcus aureus isolates from cow, goat, and ewe milk. AB - Monoclonal antibodies to Staphylococcus aureus capsular polysaccharide types 5 and 8 were used to serotype by enzyme-linked immunosorbent assay 212, 54, and 33 isolates from cow, goat, and ewe milk, respectively. Capsular types 5 and 8 accounted for 69.4% of bovine isolates and 71.5 and 78.8% of goat and ewe isolates, respectively. Type 5 was predominant in strains from bovine sources (51.4%), whereas type 8 was prevalent in strains from caprine (68.5%) and ovine (75.8%) sources. PMID- 3343314 TI - Immunoblots and plasmid fingerprints compared with serotyping and polyacrylamide gel electrophoresis for typing Clostridium difficile. AB - Two new methods for typing Clostridium difficile, immunoblotting and plasmid fingerprinting, were compared with serotyping and polyacrylamide gel electrophoresis (PAGE). Of these methods, immunoblotting was found to be the most valuable for use in a comprehensive typing system. More groups could be distinguished by immunoblotting than by serotyping or PAGE. Immunoblotting results were also more reproducible and distinctive than results by PAGE. Plasmid fingerprinting was an excellent marker for plasmid-bearing strains, but it had limited use because many isolates lacked plasmids. A unique plasmid profile observed for one group of isolates correlated with differences in phenotypic characteristics resolved by immunoblot analysis but not by serotyping or PAGE. Preliminary attempts to correlate typing results with pathogenicity of isolates were not successful but underscored the need for future studies to include careful assessment of the clinical significance of isolates. PMID- 3343315 TI - Evaluation of the campyslide agglutination test for confirmatory identification of selected Campylobacter species. AB - The utility of a rapid latex slide agglutination test (Campyslide; BBL Microbiology Systems, Cockeysville, Md.) in detecting selected Campylobacter spp. was evaluated and compared with that of conventional identification methods. Isolated colonies suggestive of Campylobacter spp. were tested directly from primary selective media after incubation at 42 degrees C under microaerophilic conditions. Stock cultures of Campylobacter jejuni (n = 27) and C. coli (n = 3) were correctly confirmed to the genus level by latex agglutination when tested in pure cultures or isolated from seeded human feces. A total of 50 fresh clinical isolates of Campylobacter spp. (45 C. jejuni and 5 C. coli) were examined, with complete agreement observed between the latex test and conventional methods. Of 173 non-Campylobacter isolates tested from primary plates, only 1 rough strain of Pseudomonas aeruginosa produced a false-positive result. Although the manufacturer recommends a 30-min antigen extraction, 1 or 5 min was found to be sufficient. Also, confirmation could be achieved within 24 h of inoculation of clinical specimens, 2 days earlier than with conventional methods. PMID- 3343316 TI - Purification, partial characterization, and seroreactivity of a genuswide 60 kilodalton Legionella protein antigen. AB - A genuswide protein antigen extracted from Legionella pneumophila serogroup 1 (strain Philadelphia 1) cells was enriched by differential pelleting and ammonium sulfate precipitation and subsequently purified with a combination of high performance size-exclusion and ion-exchange chromatography. The protein has an apparent molecular weight of 650,000 before and 63,000 after urea (5 M) treatment, as determined by size-exclusion chromatography. These proteins resolved to a single band of 60,000 after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The urea-treated protein had an isoelectric point of 5.8. This purified 60-kilodalton protein reacted with a convalescent-phase serum sample from a patient with legionellosis and rabbit immune sera prepared against each of 23 Legionella species. The 60-kilodalton protein may be useful in developing diagnostic tests for legionellosis. PMID- 3343317 TI - Possible role of capillary action in pathogenesis of experimental catheter associated dermal tunnel infections. AB - An animal model of vascular-catheter-associated dermal tunnel infections was developed to study the pathogenesis of such infections. Bacteria inoculated onto entry sites of catheters into skin could be identified by culture and Gram stain on the tips of plastic catheters (4 cm from the entry site) within 1 h of inoculation, whether the animal was inoculated at the time of insertion of the catheter or 1 week afterwards. Histological examination of dermal tunnels revealed that the introduction of bacteria preceded the development of tissue inflammation. Bacteria on entry sites of percutaneous catheters moved rapidly from the entry site into the dermal tunnel along the external catheter surface, perhaps suspended in a fluid phase and propelled by capillary action. PMID- 3343318 TI - Infection and diarrhea caused by Cryptosporidium sp. among Guatemalan infants. AB - During July 1985 to June 1986, fecal excretion of Cryptosporidium oocysts was determined prospectively in a cohort of 130 infants, aged 0 to 11 months, living in a marginal urban area of Guatemala City, Guatemala. A total of 1,280 stool specimens were examined; 158 of them were collected during episodes of diarrhea, and 1,122 were collected during symptom-free periods, every 2 to 3 weeks, from every child. Of the children, 20 (15.4%) excreted Cryptosporidium oocysts during the observation period. Of the diarrheal episodes, 13 (8.3%) were associated with Cryptosporidium sp. Of the control specimens, seven (0.6%) were positive for oocysts. Most of the infections were documented during the months of February to May, at the end of the dry season. Cryptosporidium infections are very common among Guatemalan infants and are an important cause of diarrhea and weight loss. The introduction of liquid or solid foods in the diets of the children, the presence of domestic animals (dogs, cats, or poultry), and the absence of toilet facilities in the house seem to be important risk factors for infection; also, deficient nutritional status may predispose the infected child to Cryptosporidium associated illness. PMID- 3343319 TI - Serum antibodies to pneumolysin in patients with pneumonia. AB - Serum antibodies to purified pneumolysin were determined by enzyme-linked immunosorbent assay (ELISA) in paired samples from 406 adult patients with community-acquired pneumonia and in samples from 184 healthy controls. A high sensitivity (83%) was obtained in patients with blood culture-confirmed pneumococcal pneumonia. In patients with a tentative pneumococcal diagnosis based on culture of samples from the sputum or the nasopharynx, 45% were positive by ELISA. The difference likely reflected the different relevance of cultural findings for the diagnosis of pneumococcal pneumonia. A significant rise in ELISA titer was found in 17% of the patients. When the diagnosis was also based on high titers, 25% were positive. Pneumococcal pneumonia diagnosed by the pneumolysin ELISA was significantly more common in the patients with a more severe disease and who required hospitalization (21 versus 5% for outpatients). Younger patients were more often positive for pneumococci as determined by high titers, while older patients showed titer rises. Mixed infections with other infectious agents were not uncommon. The finding of low titers in acute-phase samples from positive patients and in the youngest and oldest age groups of healthy controls were unexpected, indicating that further studies on the role of pneumolysin in pneumococcal disease are warranted. PMID- 3343320 TI - Severe progressive subcutaneous abscesses and necrotizing tenosynovitis caused by Rhodococcus aurantiacus. AB - A case of severe progressive subcutaneous abscesses and necrotizing tenosynovitis of the right arm of a 30-year-old woman caused by Rhodococcus aurantiacus is reported. PMID- 3343321 TI - Clinical evaluation of the Vitek ANI card for identification of anaerobic bacteria. AB - An evaluation of the Vitek Anaerobe Identification (ANI) card was performed with 341 bacterial isolates, including 313 clinical isolates and 28 stock strains of anaerobic microorganisms. Identifications obtained with the ANI card were compared with those determined by conventional methods. The card identified 73.2% of 149 anaerobic gram-negative bacilli, 63.6% of 44 Clostridium spp., 65.8% of 38 anaerobic nonsporeforming gram-positive bacilli, and 69.1% of 110 anaerobic cocci, with no further testing required. When genus-level identifications were included, 83.9% of the anaerobic gram-negative bacilli, 70.5% of Clostridium spp., 73.7% of the anaerobic nonsporeforming gram-positive bacilli, and 73.6% of the anaerobic cocci were identified. Nineteen isolates (5.6%) produced identifications of good confidence but marginal separation or questionable biotype, in which the correct identification was listed with one or two other possible choices and extra tests were required and suggested. A total of 28 (8.2%) were not identified and 29 isolates (8.5%) were misidentified by the ANI card. Among the commonly isolated clinically significant anaerobes, the ANI card identified 100% of 55 Bacteroides fragilis and 100% of 8 Clostridium perfringens. Use of supplemental tests and expansion of the data base to include additional strains of organisms that are difficult to separate even with conventional methods may improve the accuracy of the ANI card as a method for identification of anaerobic bacteria in the clinical laboratory. PMID- 3343322 TI - Detection of staphylococcal exfoliative toxin by slide latex agglutination. AB - A simple and rapid method in which slide latex agglutination was used was developed to detect the exfoliative toxin (ET) elaborated by clinical isolates. ET types A and B (ET-A and ET-B) were purified by plate gel isoelectrofocusing, and anti-ET sera were obtained by immunizing rabbits. A specific immunoglobulin G antitoxin was then prepared from the immunized rabbit sera by fast protein liquid chromatography, and latex particles were coated with the antitoxin. Of 74 staphylococcal strains isolated from patients with staphylococcal scalded skin syndrome, 61 strains were found to produce ET by the newborn mouse bioassay. All 61 strains were shown to be positive for ET-A and ET-B production by the slide latex agglutination method. The lowest concentration of ETs detected by the latex agglutination method was 0.5 microgram/ml, which was much lower than that detected by the double immunodiffusion method, with a sensitivity of 50 micrograms/ml. It is crucial to prove ET production by clinical isolates for the diagnosis and surveillance of staphylococcal scalded skin syndrome. The latex agglutination method is a sensitive, simple, and rapid test which can be used as an alternative to the newborn mouse bioassay. PMID- 3343323 TI - Delta toxin activity in coagulase-negative staphylococci from the bowels of neonates. AB - Coagulase-negative staphylococci are prominent in stools of neonates in some intensive care units and have been associated with necrotizing enterocolitis. A plausible mediator of bowel damage is delta-like toxin, which is produced in vitro by most coagulase-negative staphylococci, but factors influencing the expression of toxin in the bowel are unknown. We examined 105 coagulase-negative staphylococcus isolates from stools of neonates by using an enzyme-linked immunosorbent assay and detected delta toxin production by 92 isolates (88%). The amount present in 18-h broth cultures varied over 100-fold, from 933 to 125,000 ng/ml. All broths positive by enzyme-linked immunosorbent assay except one caused hemolysis of human erythrocytes. The threshold concentration for consistent cytotoxicity to fibroblasts was greater than or equal to 24,000 ng/ml. Only 56% of Staphylococcus epidermidis isolates were capable of producing this much toxin, and these were more often obtained from premature infants in intensive care than from healthy full-term infants (P = 0.003) and were more often resistant to multiple antibiotics (P less than 0.001). Cultures grown anaerobically seldom caused hemolysis (4 positive of 29 tested; P less than 0.001) because potency of the toxin was decreased (at least ninefold for S. epidermidis isolates). We conclude that only a portion of the fecal coagulase-negative staphylococci tested produced enough delta toxin in vitro to be cytotoxic, that such isolates have accumulated in our intensive care nursery, and that development of toxin-mediated bowel injury may also require a favorable redox potential within the host bowel. PMID- 3343325 TI - Evaluation of proteolytic activity to differentiate some dematiaceous fungi. AB - A total of 123 isolates of Cladosporium spp., Exophiala spp., Fonsecaea spp., Lecythophora hoffmannii, Phaeoannellomyces werneckii, Phialophora spp., Wangiella dermatitidis, and Xylohypha bantiana were tested for proteolytic activity by using 26 different formulations of gelatin, milk, casein, and Loeffler media. Other physiological properties examined included hydrolysis of tyrosine and xanthine, sodium nitrate utilization in Czapek Dox agar, and thermotolerance. Isolates of Exophiala jeanselmei, Fonsecaea compacta, Fonsecaea pedrosoi, W. dermatitidis, and X. bantiana lacked proteolytic activity. Proteolytic activity was variable among the remaining species, depending on the type of medium used. Thermotolerance had value in distinguishing some taxa. PMID- 3343324 TI - Monoclonal antibody enzyme-linked immunosorbent assay for specific identification and typing of subgroup F adenoviruses. AB - Monoclonal antibody specific for subgroup F enteric adenoviruses (EAds) was prepared by fusing P3-NS1/Ag4-1 mouse myeloma cells with lymphocytes from BALB/c mice immunized with G1105, an adenovirus type 41 (Ad41) strain. Monoclone 3F11/2H9, which specifically recognized Ad41, was successfully used as detector antibody in an enzyme-linked immunosorbent assay (ELISA). Additionally, previously prepared monoclones 5D8/2C2 and 2H6/1E11, recognizing Ad40 plus Ad41 and Ad40 alone, respectively, were used to study stool and/or tissue culture specimens from 106 patients with adenovirus-positive gastroenteritis. By ELISA, 91 had EAds (22 were Ad40 and 69 were Ad41) and 15 had non-EAds. ELISA results were in concordance with restriction endonuclease results for 38 of 39 specimens, with dot blot data for 19 of 20 specimens, and with neutralization test results for 74 of 78 specimens. ELISA was at least 10-fold more sensitive than direct electron microscopy was for the detection of EAds in stool specimens. PMID- 3343326 TI - Genetic variants of influenza A/Taiwan/1/86 cocirculating in Canada during the winter of 1986 to 1987. AB - The first isolate of influenza virus in Canada during the winter of 1986 to 1987 was a genetic variant of A/Taiwan/1/86. This genetic variant type was the predominant strain obtained from several of the western provinces. The variant strains were antigenically indistinguishable from A/Taiwan/1/86 but were remarkably distinct by T1 oligonucleotide mapping. T1 mapping of individual genome segments indicated that the variants evolved from an A/Taiwan/1/86-like virus through the accumulation of point mutation or deletion or insertion events and probably do not contain foreign genes. The relative distribution of genetic variation was approximately equal among the individual genes, with the possible exception of segments 1 or 2 that were analyzed in combination and thus could not be individually associated with the observed variation. PMID- 3343327 TI - Serotypes of Ureaplasma urealyticum isolated from normal pregnant women and patients with pregnancy complications. AB - To compare the distribution of Ureaplasma urealyticum serotypes 1 to 10 in different patient populations, the serotypes of 240 U. urealyticum strains from 207 patients were determined by the indirect immunofluorescence test by using U. urealyticum antisera 1 to 10. Strains were obtained from the following four patient groups: group 1, 24 couples in which the women had a history of recurrent spontaneous abortion; group 2, 25 patients who had their first spontaneous abortion; group 3, 14 pregnant patients with pregnancy complications (premature delivery, intrauterine death); and group 4, 138 patients with uneventful pregnancies. The serotypes most often found in these 207 patients were as follows: serotype 3, 52.2%; serotype 6, 30.3%; serotype 10, 11.4%; serotype 1, 9.5%; serotype 4, 6.5%; serotype 8, 6.5%. Serotypes 2, 5, 7, and 9 were found in less than 1% of the patients. More than one serotype was found in 16.9% of the patients. The overall distribution of the 10 serotypes in the different groups was similar, except for that of serotype 4. Serotype 4 was isolated from 20.8% of the patients in group 1 and from 5.1% of the patients in group 4 (P less than 0.01). Results of this study indicate that U. urealyticum serotype 4 can be isolated more frequently from patients with a history of recurrent miscarriages than from normal pregnant women. PMID- 3343328 TI - Antibody response in humans to influenza virus type B host-cell-derived variants after vaccination with standard (egg-derived) vaccine or natural infection. AB - Hemagglutination inhibition (HI) and neutralization tests were used to determine antibody responses to egg-derived and Madin-Darby canine kidney (MDCK)-derived influenza B virus (B/England/222/82) in paired sera from persons naturally infected with influenza B and in persons vaccinated with standard egg-derived inactivated influenza vaccine. When tested by HI, the MDCK-derived antigen gave significantly higher (8- to 12-fold) geometric mean titers (GMT) in convalescent phase sera from persons naturally infected during community outbreaks, as well as more 4-fold titer rises, than did tests with egg-derived antigen. When tested by neutralization, however, the convalescent-phase sera GMTs were only threefold higher with the MDCK-derived antigen and an equivalent number of fourfold titer rises were detected with both antigens. With postvaccine sera, the MDCK-derived antigen gave GMTs that were threefold higher than those obtained with egg-derived antigen in both the HI and neutralization tests and both antigens detected an equivalent number of fourfold titer rises in HI and neutralization tests. Sucrose gradient-fractionated egg-derived antigen showed a single peak of hemagglutinin activity corresponding to whole virions, whereas MDCK-derived antigen contained two distinct peaks of hemagglutinin activity, one of which had a lower sedimentation rate. The overall findings indicate that the egg-derived antigen in the vaccine induced HI and neutralizing antibody to both egg- and MDCK-derived variants and suggest that titers of antibody to MDCK-derived virus may be affected by the physical form of the hemagglutinin antigen. PMID- 3343329 TI - Measurement of antibodies to the Borrelia burgdorferi flagellum improves serodiagnosis in Lyme disease. AB - The isolation of Borrelia burgdorferi flagella and an enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin G (IgG) and IgM to the B. burgdorferi flagellum are described. The diagnostic performance of the flagellum ELISA for serodiagnosis of Lyme disease was compared with the performance of a traditional whole cell B. burgdorferi sonic extract ELISA. We examined sera and cerebrospinal fluid (CSF) from 56 patients with lymphocytic meningoradiculitis (Bannwarth's syndrome), the most frequent secondary-stage manifestation of Lyme disease in Europe. Two hundred healthy individuals and patients with aseptic meningitis, encephalitis, Guillain-Barre syndrome, and syphilis served as controls. The flagellum ELISA was significantly more sensitive than the sonic extract ELISA. The diagnostic sensitivities were increased from 41.1 to 76.8% (P less than 0.01) for IgG and from 35.7 to 67.9% (P less than 0.05) for IgM detection in serum. The increase in sensitivity was most pronounced in patients with a short duration of disease (less than 20 days after onset). The diagnostic specificity increased for IgG detection but was almost unaltered for IgM. The flagellum ELISA did not improve the diagnostic sensitivity of measuring antibodies to borreliae in CSF, most likely owing to the low level of unspecific antibodies in CSF compared with serum. The cross-reactivity of sera and CSF from patients with syphilis decreased significantly. The flagellum antigen of B. burgdorferi shows no strain variation, is easy to purify in sufficient quantity, and is therefore a suitable reference antigen for routine serodiagnosis of Lyme disease. PMID- 3343330 TI - Modification of potassium nitrate assimilation test for identification of clinically important yeasts. AB - The modification of an auxanographic method used in yeast species identification to determine potassium nitrate (KNO3) assimilation resulted in a simple and inexpensive KNO3 assimilation test medium. The medium provided accurate and reliable results in less than 24 h. PMID- 3343332 TI - Legionella pneumophila serogroup 14 isolated from patients with fatal pneumonia. AB - Two Legionella-like organisms, one isolated from postmortem lung tissue and the other from a bronchial aspirate, were shown by growth, physiologic, and genetic characteristics to belong to the species Legionella pneumophila. Subsequent serologic testing indicated that both strains belonged to a new serogroup, serogroup 14. PMID- 3343331 TI - Bacteremia caused by Vibrio hollisae. AB - Vibrio hollisae was recovered from the bloodstream of a 36-year-old man with chronic active hepatitis who was admitted to the hospital with signs of gastrointestinal illness. V. hollisae is an infrequent human pathogen associated with seafood ingestion. No etiologic link to seafood was demonstrated in this case report. PMID- 3343333 TI - UV red fluorescence of Veillonella spp. AB - A total of 34 clinical isolates and 7 type strains of Veillonella spp. were tested for their ability to fluoresce on various culture media. Fluorescence was medium dependent and varied among the species. Scanning absorption spectrophotometry of culture extracts showed that the absorption spectrum of the fluorescent pigment is typical of a metal-free porphyrin. PMID- 3343334 TI - Proctitis and fatal septicemia caused by Plesiomonas shigelloides in a bisexual man. AB - A case of proctitis and fatal septicemia caused by Plesiomonas shigelloides in a 42-year-old bisexual male is reported. The medical history of the patient was significant for an aortic valve replacement 3 years before but was otherwise unremarkable. A serum specimen obtained at autopsy was negative for antibody to human immunodeficiency virus by Western blot (immunoblot) analysis. P. shigelloides isolated from blood was susceptible to all antibiotics tested, agglutinated in Shigella group D antiserum, possessed a greater than 100 megadalton plasmid, and was noninvasive in a HeLa cell invasion assay. The previous reports of Plesiomonas bacteremic infections are reviewed, and possible pathogenic mechanisms are discussed. PMID- 3343335 TI - Effect of incubation temperature on growth and soluble protein profiles of motile Aeromonas strains. AB - Motile Aeromonas spp. are said to have an optimal growth temperature of 28 degrees C. We performed growth studies on 24 isolates at 29 and 37 degrees C and found that the optimal growth temperature was not necessarily 28 degrees C. We also detected temperature-dependent differences in soluble protein production in some of these strains. PMID- 3343336 TI - Aneurysm of the rabbit common carotid artery induced by periarterial application of calcium chloride in vivo. AB - Experimental aneurysmatic dilatation of the rabbit common carotid artery was induced by a single, periarterial application of calcium chloride in vivo. Vessels were fixed in situ after 3 d, 1 wk, 3 wk, 6 wk, and 12 wk by intracardiac perfusion of glutaraldehyde and tissues prepared for light, scanning, and transmission electron microscopy. Progressive focal aneurysmal dilatation was seen limited to the site of calcium application with endothelial damage and thrombus formation in areas of irregular luminal contour. Disruption of the elastic network of the intima and media was seen with varying degrees of intimal fibromuscular hyperplasia and medial disorganization. The calcium-elastic tissue complex was the focus of the inflammatory, arteriosclerotic reaction and subsequent aneurysm formation. The inflammatory cell infiltration initially included primarily neutrophils followed by lymphocytes, plasma cells, monocytes, and multinucleated giant cells. These studies support the hypothesis that disruption of the elastic tissue network of the vascular wall represents an important pathogenetic factor in the initiation of aneurysmal dilatation. In addition, the results of these studies suggest that interaction of calcium with the elastica of the arterial wall may represent an important pathogenetic factor in the initiation of giant cell arteritis. PMID- 3343337 TI - Sjogren-Larsson syndrome. Impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity. AB - Lipid metabolism was studied in cultured skin fibroblasts from patients with the inherited disorder, Sjogren-Larsson syndrome (SLS). Intact SLS fibroblasts incubated in the presence of [1-14C]palmitate accumulated more radioactive hexadecanol than did normal cells, whereas incorporation of radioactivity into other cellular lipids was unaltered. The hexadecanol content of SLS fibroblasts was abnormally elevated. Hexadecanol accumulation was not due to increased fatty alcohol synthesis nor its deficient utilization for glycerol ether synthesis. The half-life of intracellular hexadecanol loaded into SLS fibroblasts was increased (70 min) compared with normal (15 min), and intact SLS fibroblasts showed impaired oxidation of [14C]-hexadecanol to fatty acid. Fatty alcohol:NAD+ oxidoreductase, the enzyme catalyzing this reaction, was deficient in SLS fibroblasts. Mean total activity in SLS fibroblasts (n = 5) was 13% of that in normal fibroblasts, and palmitoyl CoA-inhibitable activity was 1% of normal. Fibroblasts from two obligate SLS heterozygotes had enzyme activities intermediate between that in normal fibroblasts and individuals with SLS. These results suggest that the primary defect in SLS is deficiency of fatty alcohol:NAD+ oxidoreductase. SLS represents the first inherited disorder in man associated with an isolated abnormality in fatty alcohol metabolism. PMID- 3343338 TI - Investigation of the biological effects of anti-cell adhesive synthetic peptides that inhibit experimental metastasis of B16-F10 murine melanoma cells. AB - The experimental metastasis of B16-F10 murine melanoma cells is blocked by the anti-cell adhesive pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) derived from the central cell-binding domain of fibronectin. In this report, we show that peptide treatment substantially extends the survival time for mice injected intravenously with B16-F10 cells (8/8 vs. 0/8 mice alive at 150 d), thereby demonstrating the potential efficacy of GRGDS treatment in protection against metastatic colonization. We have also examined the specificity of GRGDS activity by testing a series of related homologues for their effects on experimental metastasis. The overall profile of the relative inhibitory activities of these peptides closely matched their previously established capacity to disrupt adhesion in vitro. Lung retention studies with radiolabeled B16-F10 cells revealed an accelerated rate of cell loss from the lung 0-6 h after coinjection with the active peptide GRGDS. This early effect of GRGDS was consistent with its short circulatory half-life, which was found to be 8 min. Taken together, these results suggest that peptide mediated inhibition of pulmonary colonization is due to interference with B16-F10 cell adhesion to structures in the target organ. Possible peptide interference in tumor cell-blood cell interactions was examined in order to assess (a) possible biological side-effects of peptide treatment and (b) whether such interactions might be an alternative mechanism for GRGDS-mediated inhibition of pulmonary colonization. GRGDS was found to retain full inhibitory activity when coinjected with B16-F10 cells into mice in which platelet function was impaired by acetylsalicylic acid treatment or into thrombocytopenic mice treated with antiplatelet serum (76-93% inhibition of colony formation). These data suggest that platelet involvement in the effects of the peptide is minimal. Similarly, GRGDS was also found to be a potent inhibitor of experimental metastasis in natural killer (NK) cell-deficient beige mice (86% inhibition), thereby discounting the possibility that GRGDS artifactually enhanced NK cell activity. We conclude as a result of these studies that cell-binding fibronectin peptides are specific inhibitors of experimental metastasis that prolong survival, that they appear to function by blocking the adhesion of B16-F10 cells to structures in the target organ, and that they do not appear to act through side effects on certain metastasis-related blood cell functions. In the future, derivatives of fibronectin peptides may be potentially useful prophylactic agents for interfering with the process of metastasis. PMID- 3343339 TI - Serial evaluation of vasopressin release and thirst in human pregnancy. Role of human chorionic gonadotrophin in the osmoregulatory changes of gestation. AB - Serial studies were designed to characterized changes in osmoregulation throughout gestation. Eight women underwent a 2-h infusion of hypertonic saline before conception, during gestational weeks 5-8, 10-12, and 28-33, and then 10-12 wk postpartum. Basal plasma osmolality (Posmol) was already significantly decreased by 5-8 wk (P less than 0.001) and remained 10 mosmol.kg-1 below nonpregnant values throughout pregnancy. The apparent threshold for AVP release (defined as the abscissal intercept of the regression line relating plasma AVP [PAVP] to Posmol) was also decreased significantly throughout gestation, as was the osmotic threshold for thirst (derived from analogue scales relating desire to drink to Posmol). The decrement in osmotic thirst threshold appeared to precede that for AVP release, and consistent with this 24-h urine volumes were significantly greater at 5-8 wk gestation (P less than 0.05). The slopes of each regression equation defining PAVP vs. Posmol (whose r values ranged from 0.79 to 0.99), very reproducible before and after pregnancy, were similar at 5-8 and 10 12 wk, but were markedly reduced in the third trimester (P less than 0.001). These volunteers had randomly undergone an additional infusion before conception (both tests in the luteal phase of the menstrual cycle) when 10,000 IU of human chorionic gonadotrophin (hCG) had been given intramuscularly over a 5-d period. Serum hCG values between 0.2 and 3.3 U.ml-1 were lower than usually seen in pregnancy, but the osmotic thresholds for AVP release and thirst decreased by 3 and 4 mosmol.kg-1, respectively (P less than 0.05). Finally we studied a patient with a molar pregnancy in whom thresholds for hormone release and thirst were both decreased to values resembling normal gestation and remained so for approximately 6 wk postevacuation, only normalizing when hCG had virtually disappeared from her serum. In contrast, thresholds increased within the first two puerperal weeks in two women with normal pregnancies. These data demonstrate (a) osmotic thresholds for both AVP release and thirst decrease within the very first gestational weeks; (b) increment in PAVP per unit increase in Posmol is reduced late in gestation; and (c) hCG may be involved in the osmoregulatory changes of pregnancy. PMID- 3343340 TI - Identification of pemphigus vulgaris antigen extracted from normal human epidermis and comparison with pemphigus foliaceus antigen. AB - Immunoprecipitations of cultured keratinocyte extracts have shown that pemphigus vulgaris (PV) sera bind a polypeptide of 210,000 mol wt with disulfide-linked chains of 130,000 and 85,000 mol wt. To identify proteins in normal human skin recognized by PV antibodies, we performed immunoprecipitations of normal human epidermal extracts. All 22 PV sera tested immunoprecipitated a complex of polypeptides (PV complex) of 210,000, 130,000, and 85,000 mol wt, after reduction. One- and two-dimensional gel electrophoresis showed that the 130,000- and 85,000-mol-wt polypeptides of the PV antigen from both cultured keratinocytes and epidermis have identical charges and sizes. In addition to precipitating the PV complex, 14 of 22 PV sera also have antibodies to a calcium-sensitive epitope on a different complex of polypeptides (PF complex) which has previously been shown to be precipitated by all pemphigus foliaceus (PF) sera. The PF complex consists of polypeptides of 260,000, 160,000, 110,000, and 85,000 mol wt. Although the majority of PV sera also precipitate the PF complex, no PF sera precipitate the PV complex. Thus, PV and PF can be absolutely distinguished on a molecular level using the patients' autoantibodies. The PV and PF complexes, although distinct, have certain similarities. The 85,000-mol-wt polypeptide of each is identical. The 160,000-mol wt-peptide of the PF complex and the 130,000 mol-wt peptide of the PV complex have the same isoelectric point and both are capable of disulfide linkage to the 85,000-mol-wt polypeptide. The PV and PF complexes are closely related and may prove important in cell adhesion. PMID- 3343341 TI - In vitro adenylate cyclase-stimulating activity predicts the occurrence of humoral hypercalcemia of malignancy in nude mice. AB - A number of factors have been proposed as potential mediators of the syndrome of humoral hypercalcemia of malignancy (HHM), but to date no firm cause-and-effect relationship has been established. We attempted to establish such a relationship by determining whether the presence or absence of adenylate cyclase-stimulating activity (ACSA) in the media of cultured tumor cells predicted the occurrence of the syndrome of HHM when these cell lines were grown in nude mice in vivo. Conditioned media from 35 human renal carcinoma cell lines were surveyed for ACSA in the PTH-sensitive rat osteosarcoma 17/2.8 cell assay. 12 lines were positive (mean, 13.7-fold stimulation, range, 3.0 to 44.0), and 23 lines were negative (mean, 1.2-fold stimulation, range, 0.9 to 1.5). We were successful in establishing five of the positive and six of the negative lines in three to five nude mice per line. Mice implanted with the positive lines uniformly became hypercalcemic (mean serum calcium, 15.8 mg/dl), whereas mice implanted with the negative lines uniformly remained normocalcemic (mean serum calcium, 9.5 mg/dl), in spite of comparable mean tumor size. Acid-urea tumor extracts from each of four hypercalcemic animals contained potent in vitro ACSA (mean, 15.9-fold stimulation), while 5/5 extracts from normocalcemic animals did not (mean, 1.4 fold stimulation). Our study demonstrates that in this model system in vitro ACSA is a reliable predictive marker for HHM in vivo. Whether the protein responsible for this activity is also the mediator of the bone resorption seen in HHM remains to be demonstrated. PMID- 3343342 TI - Meal-stimulated release of methionine-enkephalin into the canine jejunal lumen. AB - Application of enkephalins to the luminal surface of the bowel augments intestinal absorption. However, to date, endogenous enkephalins have not been demonstrated within intestinal luminal fluid. To determine whether enkephalins are present in the intestinal lumen, five adult dogs had 25-cm chronic jejunal Thiry-Vella loops constructed. Dogs were studied in the awake, fasted state. Jejunal loops were perfused with isoosmotic, neutral Krebs buffer containing protease inhibitors. After basal sampling, the dogs received a high fat meat meal. Collections were made during the meal and for 60 min postprandially. Luminal met-enkephalin levels were determined by radioimmunoassay and confirmed by HPLC. HPLC separation of luminal samples demonstrated two immunoreactive peaks which co-eluted with pure met-enkephalin and met-enkephalin-sulfoxide. Basal met enkephalin outputs averaged 52 +/- 13 ng/min. The meal significantly increased mean luminal met-enkephalin output to 137 +/- 71 ng/min. During the initial 20 min postprandial period, output remained elevated (180 +/- 73 ng/min), after which it returned to basal levels. We conclude that met-enkephalin is present in the jejunal lumen, and that luminal release of this opioid is augmented by a meal. PMID- 3343344 TI - Fatty acid uptake by isolated rat heart myocytes represents a carrier-mediated transport process. AB - The mechanism by which fatty acids enter cardiomyocytes is unclear. Therefore, the influx kinetics of [3H]oleate into isolated rat heart myocytes were examined. Cells were incubated at 37 degrees C with [3H]oleate bound to albumin in various molar ratios and the initial rate of uptake (V0) was determined as a function of the unbound oleate concentration in the medium. V0 was saturable with increasing oleate concentrations incubated (Km 78 nM; Vmax 1.9 nmol X min-1 per 10(6) cells) and temperature dependent with an optimum at 37 degrees C. Furthermore, binding of [3H]oleate to isolated plasma membranes of cardiomyocytes was saturable, revealing a KD of 42 nM, and was inhibited by heat denaturation or trypsin pretreatment of the membranes. From these membranes a single 40-kD protein with high affinity for a variety of long chain fatty acids was isolated. With a monospecific antibody to this membrane protein, binding as well as cellular influx of [3H]oleate was selectively inhibited. These data indicate that at least a portion of myocardial fatty acid uptake is mediated by a specific membrane protein. PMID- 3343343 TI - Use of human surfactant low molecular weight apoproteins in the reconstitution of surfactant biologic activity. AB - Two low molecular weight (LMW) apoproteins were isolated from human pulmonary surfactant. SDS polyacrylamide gel analysis showed one protein (SP 18) to have an apparent molecular weight of 18,000 when unreduced and 9,000 D after reduction. The second protein (SP 9) migrated at approximately 9,000 D in the presence or absence of reducing agents. Both proteins contain a high number of hydrophobic amino acids. The NH2-terminal sequence of SP 18 was determined to be: NH2-phe-pro ile-pro-leu-pro-tyr-. A cDNA clone isolated from a human adult lung cDNA library contained a long open reading frame encoding at an internal position the human SP 18 amino-terminal sequence. Mixtures of phospholipids (PL) and SP 9 and SP 18 were assessed for their capacity to reduce surface tensions on a pulsating bubble surfactometer. The addition of 1% apoprotein resulted in a reduction of surface tension after 15 s from 42.9 dyn/cm for PL alone to 16.7 and 6.3 dyn/cm for preparations containing SP 9 and SP 18, respectively. In vivo assessment of reconstituted surfactant activity was performed in fetal rabbits. Reconstituted surfactant consisting of PL + 0.5% SP 18 instilled intratracheally at delivery resulted in a marked increase in lung compliance, while the incorporation of 0.5% SP 9 yielded a moderate increase. These data show the ability to produce biologically active surfactant by the addition of isolated LMW apoproteins to defined PL. PMID- 3343345 TI - Properties of highly purified leukotriene C4 synthase of guinea pig lung. AB - Leukotriene C4 (LTC4) synthase, which conjugates LTA4 and LTA4-methyl ester (LTA4 me) with glutathione (GSH) to form LTC4 and LTC4-me, respectively, has been solubilized from the microsomes of guinea pig lung and purified 91-fold in four steps to a specific activity of 692 nmol/10 min per mg protein using LTA4-me as substrate. LTC4 synthase of guinea pig lung was separated from microsomal GSH S transferase by Sepharose CL-4B chromatography and further purified by DEAE Sephacel chromatography, agarose-butylamine chromatography, and DEAE-3SW fast protein liquid chromatography. It was also differentiated from the microsomal GSH S-transferase, which utilized 1-chloro-2,4-dinitrobenzene as a substrate, by its heat lability and relative resistance to inhibition by S-hexyl-GSH. The Km value of guinea pig lung LTC4 synthase for LTA4 was 3 microM and the Vmax was 108 nmol/3 min per microgram; the Km values for LTA3 and LTA5 were similar, and the Vmax values were about one-half those obtained with LTA4. The conversion of LTA4 me to LTC4-me was competitively inhibited by LTA3, LTA4, and LTA5, with respective Ki values of 1.5, 3.3, and 2.8 microM, suggesting that these substrates were recognized by a common active site. IC50 values for the inhibition of the conjugation of 20 microM LTA4-me with 5 mM GSH were 2.1 microM and 0.3 microM for LTC4 and LTC3, respectively. In contrast, LTD4 was substantially less inhibitory (IC50 greater than 40 microM), and LTE4 and LTB4 had no effect on the enzyme, indicating that the mixed type product inhibition observed was specific for sulfidopeptide leukotrienes bearing the GSH moiety. PMID- 3343346 TI - Role of the direct and indirect pathways for glycogen synthesis in rat liver in the postprandial state. AB - The pathway for hepatic glycogen synthesis in the postprandial state was studied in meal-fed rats chronically cannulated in the portal vein. Plasma glucose concentration in the portal vein was found to be 4.50 +/- 1.01 mM (mean +/- SE; n = 3) before a meal and 11.54 +/- 0.70 mM (mean +/- SE; n = 4) after a meal in rats meal-fed a diet consisting of 100% commercial rat chow for 7 d. The hepatic portal difference of plasma glucose concentration showed that liver released glucose in the fasted state and either extracted or released glucose after feeding depending on plasma glucose concentration in the portal vein. The concentration of portal vein glucose at which liver changes from glucose releasing to glucose uptake was 8 mM, the Km of glucokinase [E.C. 2.7.1.12]. The rate of glycogen synthesis in liver during meal-feeding was found to be approximately 1 mumol glucosyl U/g wet wt/min in rats meal-fed a 50% glucose supplemented chow diet. The relative importance of the direct vs. indirect pathway for the replenishment of hepatic glycogen was determined by the incorporation of [3-3H,U-14C]glucose into liver glycogen. Labeled glucose was injected into the portal vein at the end of meal-feeding. The ratio of 3H/14C in the glucosyl units of glycogen was found to be 83-92% of the ratio in liver free glucose six minutes after the injection, indicating that the majority of exogenous glucose incorporated into glycogen did not go through glycolysis. The percent contribution of the direct versus indirect pathway was quantitated from the difference in the relative specific activity (RSA) of [3H] and [14C]-glycogen in rats infused with [3-3H,U-14C]glucose. No significant difference was found between the RSA of [3H]glycogen and [14C]glycogen, indicating further that the pathway for glycogen synthesis in liver from exogenous glucose is from the direct pathway. Our results do not support the thesis that the majority of liver glycogen is synthesized from glucose-6-phosphate derived from gluconeogenesis. Reasons for the discrepancy between current findings and other reports supporting the indirect pathway for glycogen synthesis in the liver are discussed. PMID- 3343348 TI - Inhibition of diabetes in BB rats by virus infection. AB - BB rats serve as a model for human insulin-dependent diabetes mellitus (IDDM), since without insulin treatment, most 60-140-d-old animals die within 1 to 2 wk of developing polyuria, polydypsia, hyperglycemia, and hypoinsulinemia. Lymphoid cells accumulate in the islets of Langerhans and beta cells undergo destruction. We report that inoculation of such BB rats with lymphocytic choriomeningitis virus (Armstrong strain, clone 13) reduces over a prolonged period the incidence of IDDM, normalizes the concentration of blood sugar and pancreatic insulin, prevents the mononuclear cell infiltration in the islets of Langerhans, and for a short time after inoculation alters T lymphocyte subsets. Thus, a virus might be programmed to carry out useful functions. PMID- 3343347 TI - Multiple crm- mutations in familial hypercholesterolemia. Evidence for 13 alleles, including four deletions. AB - The low density lipoprotein (LDL) receptors in fibroblasts from 132 subjects with the clinical syndrome of homozygous familial hypercholesterolemia were analyzed by immunoprecipitation with an anti-LDL receptor monoclonal antibody. 16 of the 132 cell strains (12%) synthesized no immunodetectable LDL receptor protein, indicating the presence of two mutant genes that failed to produce cross-reacting material (crm- mutations). DNA and mRNA from 15 of the 16 crm- patients, representing 30 crm- genes, were available for further study. Haplotype analysis based on 10 restriction fragment length polymorphisms (RFLPs) suggested that the 30 crm- genes represent 13 mutant alleles. Four of the alleles produced no mRNA. Three of these four mRNA- alleles had large deletions ranging from 6 to 20 kb that eliminated the promoter region of the gene. The fourth mRNA- allele did not contain any deletion or alteration in the promoter sequence; the reason for the mRNA- phenotype was not apparent. Nine alleles were positive for mRNAs, of which three encoded mRNAs of abnormal size. One of the abnormal mRNAs was produced by a gene harboring a deletion, and another was produced by a gene with a complex rearrangement. The third abnormal-sized mRNA (3.1 kb larger than normal) was produced by an allele that had no detectable alterations as judged by Southern blotting. The other six mRNA+ alleles appeared normal by Southern blotting and produced normal-sized mRNA but no receptor protein. The current studies demonstrate that mRNA analysis coupled with haplotype determination by Southern blot analysis can be used to classify crm- mutations at a genetic locus where multiple alleles exist. PMID- 3343349 TI - Effects of a synthetic peptide of a parathyroid hormone-related protein on calcium homeostasis, renal tubular calcium reabsorption, and bone metabolism in vivo and in vitro in rodents. AB - A synthetic peptide corresponding to the first 34 amino acids of the parathyroid hormone-related protein (PTH-rP) produced by a human tumor associated with hypercalcemia was examined for skeletal and renal effects on calcium metabolism in vivo and in vitro. These effects were compared with those of human parathyroid hormone (1-34), hPTH (1-34). Equal doses of PTH-rP(1-34) and hPTH(1-34) produced equivalent stimulation of adenylate cyclase in vitro in bone cells and kidney cells and tubules. Subcutaneous injection of PTH-rP(1-34) in mice caused a significant dose-related increase in blood ionized calcium similar to that seen with hPTH(1-34) at equivalent doses. Repeated injections of equal doses of both peptides caused sustained hypercalcemia which was significantly greater in PTH rP(1-34)-treated mice, although each induced comparable increases in histomorphometric indices of osteoclastic bone resorption. PTH-rP(1-34) and hPTH(1-34) also caused similar increases in bone resorption when incubated with fetal rat long bones in organ culture. Infusion of either peptide into thyroparathyroidectomized rats suppressed urinary calcium excretion and increased urinary excretion of cyclic AMP. PTH-rP appears to have similar effects to those of PTH on the skeleton, the kidney, and overall calcium homeostasis. PMID- 3343352 TI - Revalidation and expansion of an adolescent substance abuse screening measure. AB - The perceived-benefit-of-drinking scale has been developed to assess reasons for drinking in an adolescent population. In this study, the self-administered questionnaire, which has been expanded to include a reason-for-drug-use scale, was completed by 1363 junior and senior high school students. A comprehensive battery of analytic techniques was used to investigate the performance of these perceived-benefit scales on this larger and wider age-range sample. The results confirmed the reliability and validity of the instrument. The findings showed the two scales to perform well across a range of sociodemographic and age groups. These data reassert the strength of the approach and support the instrument's potential as a tool for clinically assessing adolescent substance use. PMID- 3343351 TI - Observations of a support group for parents of children with severe bronchopulmonary dysplasia. AB - Parents of children with bronchopulmonary dysplasia (BPD) suffer severe stress and anxiety. In order to provide a group of peers and ready access to caregivers, a support group was developed for the families of children with severe BPD. Fifty percent of invited families attended 1 to 11 monthly meetings. Those attending were primarily upper middle social class, white, married parents with a good visiting record. Members initially focused on specific topics (medical and developmental problems), but later discussions were oriented to psychosocial problems. Many parental anxieties had never previously been discussed with staff members. Commonly, parents complained about not understanding the medical care system. The parents were usually aware of the death of a child with BPD prior to the meeting and dealt with their feelings in the group discussion. Continuing interactions outside the hospital were common. The development of similar groups in other hospitals should be encouraged. PMID- 3343353 TI - Concerns regarding the indirect assessment for drug abuse among adolescents. PMID- 3343350 TI - Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese. AB - Complete adenine phosphoribosyltransferase (APRT) deficiency causes 2,8 dihydroxyadenine urolithiasis. In previous reports, analysis of the kinetic properties of APRT from APRT-deficient Japanese subjects revealed strikingly similar abnormalities suggesting a distinct "Japanese-type" mutation. In this paper, we report studies of 11 APRT-deficient lymphoblast cell lines. Nucleotide sequence analysis of APRT genomic DNA from WR2, a Japanese-type homozygote, identified a T to C substitution in exon 5, giving rise to the substitution of threonine for methionine at position 136. RNase mapping analysis confirmed this mutation in WR2 and revealed that six other Japanese-type homozygotes carry the same mutation on at least one allele. The remaining Japanese subject, who does not express the Japanese-type phenotype, did not demonstrate this mutation. Southern blot analysis showed that all seven Japanese-type subjects were confined to one TaqI restriction fragment length polymorphism (RFLP) haplotype. These studies provide direct evidence for the nature of the mutation in the Japanese type APRT deficiency. PMID- 3343354 TI - Sudden infant death syndrome revisited. PMID- 3343355 TI - Pediatric acquired immune deficiency syndrome and the prevention of mental retardation. PMID- 3343357 TI - Self-reported stress symptoms in farmers. AB - The self-reported incidence of stress-related symptoms was studied in 817 farm men and women and 109 urban residents. Close to 50% of the farm sample reported the frequent to constant occurrence of the symptoms of trouble relaxing, loss of temper, and fatigue. Over 30% of the farmers reported similar occurrence rates for six additional symptoms. Self-reported symptom rates were significantly higher in farm women than in farm men, higher in younger farmers, higher in mixed farming operations, and higher in farmers who were holding off-farm employment. Symptom scores were significantly higher in the farmers compared to the urban sample. A stepwise discriminant analysis showed that scores on five symptoms were able to distinguish meaningfully between farm and urban groups. It was suggested that the chronic stress associated with the current farm financial crisis may be causing a high self-reported incidence of symptoms among farmers. PMID- 3343356 TI - Temperament in full-term and preterm infants: stability over ages 6 to 24 months. AB - Temperament stability over successive ages in the first 2 years of life was evaluated for 109 full-term and 81 preterm infants who were assessed at 6, 9, 12, 18, and 24 months. At each age, the infant was engaged in a series of age appropriate vignettes in the laboratory, using a structured sequence of activities. Ratings were made of emotional tone, attentiveness, activity, and orientation to staff. Correlations indicated that, for full-term infants, there was significant stability across ages (6 to 9 months, 9 to 12 months, 12 to 18 months, and 18 to 24 months) for all variables. For preterm infants, stability across ages generally was not observed until later infancy, or was sporadic. The findings indicated that, for full-term infants, stable aspects of temperament were apparent during the first year of life. In contrast, individual differences were not as clearly defined for preterm infants until later ages. PMID- 3343358 TI - Contemporary norms for the Wiggins Content Scales: a 45-year update. AB - The Wiggins Content Scales (WCS) continue to be popular among clinicians. However, MMPI profile patterns across the basic scales have shown significant changes since the inception of the MMPI in 1937. Therefore, the possibility of similar changes on the WCS was investigated. Significant differences between the old norms and a large, randomly selected contemporary normal sample (N = 1,408) were found on 9 of the WCS for women and on 5 for men. New normative tables are presented as an aid for clinicians who use the WCS. PMID- 3343360 TI - Self-esteem and negative affect. AB - It was hypothesized that the Profile of Mood States (bipolar form) measures two higher-order dimensions: Positive and Negative Affect. It also was conjectured that subjects low in self-esteem report more Negative Affect than those high in self-esteem. POMS and the Self-Attitude Inventory were administered to 102 high school students. A principal component analysis of the 12 half-scale scores of POMS isolated the two affect dimensions postulated. Tests also showed that subjects low in Confidence report significantly greater Negative Affect than subjects high in Confidence. Thus, the Watson-Tellegen theory of affect is supported, and Negative Affect is linked to self-esteem. PMID- 3343359 TI - A semantic differential mood scale. AB - A set of bipolar semantic differential type adjective scales were constructed to assess five mood states. The response format chosen serves to control for response bias, reduces the number of items by half, and measures both positive and negative affect. Each of the six bipolar mood states hypothesized was defined by seven five-point items. Two studies were conducted on samples of high school boys (N = 210); both confirmed the presence of five mood factors: Cheerful Depressed, Energetic-Tired, Good natured-Grouchy, Confident-Unsure, and Relaxed Anxious. The mood state factors isolated were compared with the scales in the Eight State Questionnaire and Bipolar POMS. PMID- 3343361 TI - Test-retest reliability of the Hopelessness Scale and its items in a university population. AB - In a study that used 149 university undergraduates and a 3-week test-retest interval, the stability of the Hopelessness Scale was examined. Scale scores and item responses demonstrated high test-retest reliabilities. Additional analyses indicated significant sex differences on the Hopelessness Scale. It was concluded that the Hopelessness Scale's stability fulfills a prerequisite for it to be a predictor of long-term suicidal risk. PMID- 3343363 TI - MMPI scales for DSM-III personality disorders: a preliminary validation study. AB - A preliminary investigation of the external validity of MMPI scales designed to measure certain DSM-III Personality disorders (N = 108) is reported. Results indicate that many of these scales are effective for discriminating clinically diagnosed personality disorders from control subjects (N = 640). PMID- 3343362 TI - A summary of the reliability and stability of MMPI scales. AB - A sample of MMPI research published between 1970 and 1981 was analyzed to yield reliability and stability estimates for the MMPI scales. In fundamental agreement with previous research, moderately high levels of reliability and stability were found for all scales. Reliability values ranged from .71 to .84; stability values ranged from .63 to .86. These findings are based on thousands of adult subjects from college, psychiatric, medical, alcohol or drug rehabilitation, and prison populations. The present scale estimates have wide generalizability and, therefore, should be of value to clinicians and researchers in various settings. PMID- 3343364 TI - The factor structure of the eating disorders inventory. AB - The Eating Disorders Inventory (EDI) is a promising new measure of the cognitive and behavioral characteristics of anorexia nervosa and bulimia, although the replicability of its eight subscales has not been evaluated. Therefore, a factor analysis of the EDI was carried out that used the FACTOREP procedure. The results, using non-patient responses, did not confirm the original eight subscales, but did show three clear and replicable factors to exist. It was suggested that these may be of clinical value as preliminary screening measures or as indices of response to treatment, although further validation would be required to establish their utility. PMID- 3343365 TI - Intensionality in the irrational beliefs-intellectual performance relationship. AB - This study tested the hypothesis that certain semantic processes may be responsible for the previously observed inverse relationship between the endorsement of Ellis's irrational beliefs and measures of intellectual performance. The IS of Identity Scale, a measure of intensional thinking, was administered to 134 male and female entering college freshmen, along with a list of Ellis's irrational beliefs, the Developmental Test of Reading Skills, and locally constructed tests of writing and mathematics. A multiple-regression analysis showed that irrationality uniquely accounted for 13% of reading variance (p less than .001) and none of the variance in the other variables. Intensionality was not associated uniquely with any of the variables and seemingly played no part in the irrationality-intellectual performance relationship. PMID- 3343366 TI - The Fargo Map Test: a standardized method for assessing remote memory for visuospatial information. AB - At present, there is no standardized method for assessing remote memory (RM) for visuospatial information in humans. The Fargo Map Test (FMT) uses knowledge of the locations of geographical features in regions of the country in which subjects currently live and formerly resided to provide a measure of this aspect of RM. Two different formats of the FMT have been developed, which differ in their demands for fine motor skill, ease of scoring, and in the amount and nature of geographical knowledge that can be measured. Preliminary findings suggest that both formats are equally sensitive to the influences of gender and age in normal subjects. Furthermore, knowledge of the geography of regions of prior residence appears to be stable over a period of at least 15 years. PMID- 3343368 TI - Converting Shipley Institute of Living Scale scores to IQ: a comparison of methods. AB - A sample of 486 male veteran psychiatric patients at a Veterans Administration medical center were used to compare five different methods of estimating IQs from Shipley Scale scores. The methods were: (1) Grayson VA norms; (2) Paulson and Lin Table 5; (3) age-corrected Paulson and Lin Table 4; (4) Zachary et al. continuous age norms; and (5) Tamkin and Jacobsen method applying age-correction to Paulson and Lin's Table 5. An intercorrelation matrix, mean, standard deviation, and range were computed for all five IQ estimates. The same analyses were computed separately by age decade. The results suggest the advisability of using age corrected norms for estimating IQ from the Shipley Scale. Norms uncorrected for age result in underestimates for older subjects. The Zachary et al. and Tamkin and Jacobsen methods yielded highly similar results. PMID- 3343367 TI - Estimating WAIS IQ from the Shipley Institute of Living Scale: a replication. AB - This study represents a replication of the linear regression techniques and continuous norming used to estimate age-adjusted WAIS IQ from the Shipley Institute of Living Scale. The sample was composed of 125 male, right-handed, psychiatric patients, who represented five age decades between 20 and 70. The overall correlation coefficient between observed and estimated IQs was .79. The data suggest that the prediction formula is robust across all five age groups. The data also show the Shipley estimated WAIS Full Scale IQ to be somewhat better when compared with the continuously normed WAIS IQ than when compared with the WAIS tabled norms. Thus, the present results provide support for the utility of the continuous norming procedure for predicting WAIS IQ from the Shipley and argue for its use. PMID- 3343369 TI - Personality and biographic data that characterize men who abuse their wives. AB - Personality and background data were presented on 250 men enrolled in group treatment for wife abuse. Follow-up data were available for 44 of these men. Standard measures available included 16PF, PSI, and MAST for personality and alcoholism. Background data included self-reports of level of violence, income, education, occupation, and violence in family of origin. Prior findings that link alcoholism and violence in family of origin to current family violence were confirmed. Level of violence was found to be related to more general pathologies, to alcoholism, and to prior family violence. Otherwise, no typology of violent men emerged in terms of pathology or general personality. PMID- 3343370 TI - Differences in psychological need hierarchies between black and white drug addicts. AB - A total of 109 Black and White heroin and cocaine addicts in treatment for drug abuse were compared on the Adjective Checklist (ACL). We found that the White addict had a significantly different pattern of needs than did the Black addict, characterized by more psychological dependence, distress, and maladjustment. Consistent with the MMPI literature in this area, the ACL provides an accurate evaluation of personality dimensions among drug addicts, and White addicts are more psychologically maladjusted than Black addicts. PMID- 3343371 TI - Validation of a brief form of the Competency Screening Test. AB - This study investigated the predictive validity of a brief, five item version of the Competency Screening Test (CST). Subjects were 140 defendants admitted to the forensic unit of a state hospital for evaluation of competency to stand trial. Scores on the brief version of the CST were used to predict competency decisions made by a multidisciplinary treatment team. In addition, the predictive validity of the brief version was compared with that of the standard CST. Both versions of the test exhibited significant relationships with staff decisions. However, the reliability of the brief version was lower than that of the standard CST because of the smaller number of items involved. Although the brief CST should not provide the sole basis for a decision about competency, it may be a useful component of a comprehensive program of competency evaluation, particularly when a rapid, preliminary screening instrument is needed. PMID- 3343372 TI - Urease activity of Campylobacter pylori. PMID- 3343373 TI - Dipstick screening for bacteriuria. PMID- 3343374 TI - Management of women with abnormal cervical smears: supplement to terminology in gynaecological cytopathology. PMID- 3343375 TI - Ultrastructural and immunocytochemical study of a case of invasive cribriform breast carcinoma. AB - A case of recurrent invasive cribriform carcinoma of the breast mimicked the histological and mucin staining characteristics of adenoid cystic carcinoma. The diagnosis was based on negative immunocytochemical staining for laminin and ultrastructural evidence of luminal differentiation by cells lining the cystic spaces. Accurate characterisation of this type of breast tumour can be facilitated by retrospective immunocytochemical or ultrastructural examination, or both. PMID- 3343377 TI - Histopathology of benign non-palpable breast lesions identified by mammography. AB - Over four years the histological features of benign breast diseases, diagnosed after biopsy of non-palpable mammographic abnormalities, were reviewed and correlated with the mammographic appearances. The histological features were compared with those from all other benign biopsy specimens taken during the same period. The incidence of sclerosing adenosis and microcalcifications was considerably higher in the group of non-palpable mammographic lesions; fibrous disease of the breast and radial scar (infiltrating epitheliosis) were also more common. There was no difference in the incidence of epithelial hyperplasia between the two groups. Correlation with the mammographic appearances showed that microcalcification was most often associated with blunt duct adenosis and that stromal distortion or masses were most often caused by fibrous disease. PMID- 3343376 TI - Retrospective study of prognostic importance of DNA flow cytometry of urinary bladder carcinoma. AB - Cellular DNA content was determined by flow cytometry on routinely processed paraffin sections of 61 primary and untreated transitional cell carcinomas of the urinary bladder, and correlated with tumour grade and stage and clinical follow up. All 16 (25%) grade 1 carcinomas were diploid and all 11 (20%) grade 3 tumours were aneuploid. The 34 (55%) grade 2 carcinomas comprised 13 (40%) diploid and 21 (60%) aneuploid cases. Among the 37 superficial carcinomas (stage Ta and T1), 25 (65%) were diploid; 20 (85%) of the 24 advanced tumours (stage T2 to T4) had aneuploid tracings. Ploidy was a significant prognostic indicator (p: 0.006) of five year survival. The initial presence of aneuploidy in superficial bladder carcinoma (stage Ta and T1) is a strong argument for more aggressive treatment than is customary. PMID- 3343378 TI - Brain damage in fatal non-missile head injury without high intracranial pressure. AB - As part of a comprehensive study of brain damage in 635 fatal non-missile head injuries, the type and prevalence of brain damage occurring in the absence of high intracranial pressure were analysed. Of 71 such cases, 53 sustained their injury as a result of a road traffic accident; only 25 experienced a lucid interval. Thirty eight had a fractured skull, a mean total contusion index of 12.9 and diffuse axonal injury in 29: severe to moderate ischaemic damage was present in the cerebral cortex in 25, brain swelling in 13, and acute bacterial meningitis in nine. The prevalence and range of brain damage that may occur in the absence of high intracranial pressure are important to forensic pathologists in the medicolegal interpretation of cases of fatal head injury. PMID- 3343379 TI - Serum C reactive protein in infective endocarditis. AB - C reactive protein (CRP) was measured serially in 29 patients with infective endocarditis. Twenty one patients were initially treated with antimicrobial drugs. In 13, serial measurement of CRP concentrations showed a progressive return to normal (less than 10 mg/l), which correlated with a satisfactory recovery. Of the remainder (eight patients), five had persistently high concentrations of CRP, indicating a failure to respond to antimicrobial treatment alone. Two of these five patients died and three underwent valve replacement. Of 11 patients treated with antibiotics and valve replacement, CRP concentrations returned to normal in nine. Two patients had infective complications and the CRP concentration did not return to normal. A transient rise in CRP concentration during an otherwise uneventful fall to normal was a sign of allergic reaction in two and of intercurrent infection in three more patients. Serial measurements of CRP concentrations in patients with infective endocarditis may be useful to monitor treatment and also to detect other infections and complications. PMID- 3343381 TI - What is colitis? Statistical approach to distinguishing clinically important inflammatory change in rectal biopsy specimens. AB - Measurements of mucosal dimension, architecture, and cell counts in both lamina propria and epithelium were made on rectal biopsy specimens from 20 patients with irritable bowel syndrome ("normal" controls); 54 patients with ulcerative colitis, Crohn's disease, and non-specific proctitis; eight patients with small bowel Crohn's disease; and 34 in whom the rectal biopsy specimen was not diagnostic. Discriminant analysis was applied to multiple variables based on the measurements, and three variables were identified as of high predictive value. The most powerful discriminant was increased lamina propria cellularity in all forms of chronic colitis. The ratios of surface length to mucosal length and of surface epithelial height to crypt epithelial height also emerged as discriminants. Chronic inflammatory bowel disease was distinguished from normal in 95% of cases with a definite pathological diagnosis, and 85% of borderline cases were correctly classified as either normal or inflammatory when judged by the final diagnosis after follow up. This study provides a basis for automated diagnosis of rectal biopsy specimens and provides objectively validated criteria which can also be applied in routine histological diagnosis. PMID- 3343382 TI - Campylobacter associated gastritis in patients with non-ulcer dyspepsia. AB - Gastric biopsy specimens from 109 patients with non-ulcer dyspepsia were retrospectively examined. Sixty one patients had gastritis and there was a strong correlation with the presence of Campylobacter pyloridis. Ninety eight per cent were positive in large numbers for C pyloridis by histological examination or by culture, or both. Of 48 patients with normal histological results, 21 had evidence of C pyloridis by histological examination or culture, or both, but in small numbers. It is concluded that there is a quantitative rather than a qualitative association between C pyloridis and gastritis. PMID- 3343380 TI - Fifty cases of human immunodeficiency virus (HIV) infection: immunoultrastructural study of circulating lymphocytes. AB - The peripheral lymphocytes of 50 cases of human immunodeficiency virus (HIV) infection (13 of acquired immune deficiency syndrome (AIDS), 17 of AIDS related complex (ARC), and 20 healthy carriers) were studied immunoultrastructurally. The prevalence of "tubuloreticular structures" and "tubular confronting cisternae" increased with the progression of the disease. Numerous tubular confronting cisternae were noted in patients presenting with a high serum acid labile alpha interferon values. The patients with depressed natural killer cell activity were characterised by circulating immature natural killer cells with abundant multivesicular bodies that were devoid of "parallel tubular arrays". With an immunogold staining technique the location of HIV antigen was detected ultrastructurally, both at the surface of "hand-mirror" natural killer cell lymphocytes and inside vacuolised cells, probably corresponding to infected T4 lymphocytes. These findings indicate the usefulness of electron microscopic techniques in evaluating the pathology and the pathogenetic outcome of AIDS. PMID- 3343384 TI - Use of the tracheostoma valve in the marking of contrastive stress and sentence intonation. AB - Two proficient tracheoesophageal speakers experienced in use of the tracheostoma valve (TSV) produced a total of 64 examples of "Bev loves Bob." These productions varied with location of contrastive stress, type of sentence intonation, and use of TSV. Thirty-four listeners judged the utterances in terms of stress placement and intonation contour simultaneously. An analysis of variance of the perceptual results indicated that TSV use reduced speaker ability to signal the two suprasegmental features; however, locus of the suprasegmental features, particularly stress placement, appeared to exert a stronger effect. PMID- 3343383 TI - Tuberculous lymphadenitis associated with human immunodeficiency virus (HIV) in Uganda. AB - Sixteen adults presented with lymphadenopathy which was tuberculous on biopsy; they were all seropositive for human immunodeficiency virus (HIV-1), but none had the clinical criteria of the acquired immunodeficiency syndrome (AIDS). The biopsy specimen showed caseating tuberculosis, with scanty or no visible acid fast bacilli in seven cases; the remaining nine had a poor cellular reactivity with numerous bacilli. Antituberculous chemotherapy for two months reduced the lymphadenopathy. Two patients subsequently developed AIDS. Mycobacterial cultures were not performed, but the infection was almost certainly Mycobacterium tuberculosis. The space-time clustering of tuberculous lymphadenitis now seen in Kampala, and the unusual non-reactive histopathology, are typical of the impairment of cellular immunity induced by HIV infection. PMID- 3343385 TI - Somatization, paranoia, and language. AB - Somatization and paranoia are circumscribed distortions of reality that are impervious to the normative process of consensual validation. These distortions are often postulated as a means of bolstering lowered self-esteem. We used computerized content analysis of the free speech of patients with these disorders in order to identify and compare dimensions of self-concept reflected in their lexical choices. Interestingly, patients with these disorders differed in the themes prominent in their speech. The higher frequency categories used by the somatization disorder group conveyed an overwhelming sense of negativism, distress, and a preoccupation with an uncertain self-identity. In contrast, the categories used by the paranoid patients portrayed an artificially positive, grandiose self-image and a defensive abstractness. Our exploratory analysis suggests that circumscribed distortions of reality in somatization and paranoid disorders are not associated with the same common defensive style attempting to bolster self-esteem. PMID- 3343386 TI - A comparison of the learnability of manual sign and Blissymbolics with nonhandicapped adults. AB - Although advocates exist for teaching either Blissymbolics or manual sign to language-impaired students, relatively few empirical data exist on the learnability of the two systems. The present study compared the learning of a list of 20 Blissymbols and comparable ASL signs in a controlled paired-associate (P-A) paradigm. Blissymbols were learned significantly faster than manual sign particularly in early learning trials. Results are discussed in terms of the memory requirements of the two systems and their relationship with sign/symbols learning. PMID- 3343387 TI - Perception of syllable stress in esophageal speech. AB - This study is part of a larger investigation designed to assess the ability of esophageal speakers to effect systematic changes in listener perceptions of syllable stress. Ten male functional esophageal speakers and ten normal speakers were instructed to produce 25 repetitions of the disyllable/mama/ using five different conditions of syllable stress, ranging from strong first syllable stress through strong second syllable stress. Nine normal listeners judged both relative and absolute syllable stress of the disyllables, using a nine-point scale for each syllable. The results indicated that highly reliable judgments can be made when judging relative and absolute syllable stress in disyllables produced by both normal and esophageal speakers. In response to experimenter direction, both normal and esophageal speakers are able to effect systematic changes of direction and degree in listener perceptions of relative stress. PMID- 3343388 TI - The use of a pragmatic protocol with normal preschool children. AB - The purpose of the present study was to examine the use of language functions in a structured setting in normal preschool children. Subjects were 240 males and females between the ages of two and five years. Results indicated statistically significant differences in the appropriateness of responses among several different age groups. The results are discussed relative to the assessment of the preschool child with a possible language disorder. PMID- 3343389 TI - Structure-function relationships in the rat brainstem subnucleus interpolaris: II. Low and high threshold trigeminal primary afferents. AB - Prior studies indicate that vibrissa, guard hair, hairy skin, mucosa, and nociceptive trigeminal primary afferents give rise to morphologically distinct terminal arbors in the medullary dorsal horn. The present study describes the extent to which similar structure-function relationships exist in the rostrally adjacent subnucleus interpolaris (SpVi). Seventy-three axons were physiologically characterized and visualized by standard intra-axonal HRP labeling techniques. They responded to guard hair (GH) or vibrissa (VIB) deflection; gentle pressure applied to hairy skin (HS), glabrous skin (GS), lingual mucosa (LM), or an incisor (PER); or a noxious pinch of the face (NOX). Response latencies to trigeminal ganglion shocks were equivalent for all categories with low threshold receptive fields (mean = 0.44 ms), and these were significantly shorter than those of fibers with high threshold NOX receptive fields (mean = 0.88 ms). All axons gave off transversely oriented collaterals into SpVi with rostrocaudal discontinuities in their arbors. Collaterals were topographically organized. Axons innervating the rostral mouth and face terminated medially, and those that supplied the caudal face innervated successively more lateral SpVi. The dorsal face was represented in the ventral SpVi, whereas the ventral face and mouth were represented more dorsally. This transverse topography extended largely throughout the rostrocaudal extent of SpVi. VIB, GH, GS, and LM collaterals had similar configurations with circumscribed arbors. HS, PER, and NOX arbors had a "stringy" shape without a clear terminal focus, save for the fact that PER and NOX collaterals often terminated in rostrally displaced substantia gelatinosa at the level of the caudal SpVi. Analysis of variance, considering only those data from mystacial VIB, GH, and HS fibers, indicated significant differences for all of the following measures: number of collaterals, number of boutons per collateral, arbor area, arbor circumference, and arbor circularity (form factor). A similar analysis, considering all fiber types, indicated significant differences for only the following measures: number of collaterals, arbor area, and arbor circumference. Individual group comparisons between the more heavily sampled functional categories indicated that GH afferents had significantly fewer collaterals, fewer boutons per collateral, smaller arbor area, shorter arbor circumference, and more circular arbors than those of HS axons. VIB fibers tended to fall between GH and HS afferents with respect to number of collaterals, arbor area, circumference, and circularity. The remaining functional groups were not as orderly.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3343391 TI - Ultrastructural organization of normal and transplanted rat fascia dentata: II. A quantitative analysis of the synaptic organization of intracerebral and intraocular grafts. AB - As part of an ultrastructural analysis of the normal rat fascia dentata and intracerebral and intraocular dentate transplants the synapses in the dentate molecular layer were quantified. Hippocampal and dentate tissue from 21-day-old rat embryos were grafted into the brain of developing and adult rats and to the anterior eye chamber of adult rats. After 100 or 200 days of survival the recipient rat brains and the recipient eyes were processed for electron microscopy, and the graft dentate molecular layer with the adjacent granule cell layer selected for ultrastructural analysis. Tissue from the dentate molecular layer of normal adult rats served as controls. The dentate synapses were classified as asymmetric (Gray's type 1) or symmetric (Gray's type 2), and according to the postsynaptic element (cell body, dendritic shaft, dendritic spine). The spine synapses were further classified into simple and complex types according to the spine-terminal configuration. Also, the length of synaptic contacts of the individual synaptic types was measured in some grafts, just as the percentage of the cross sectional area of the neuropil covered by blood vessels. The results showed that the synaptic density, expressed as number per unit area of neuropil, to a large extent was the same within the different parts of the normal dentate molecular layer. Compared with this the synaptic density was reduced with 16.4% in dentate molecular layer of the intracerebral graft, primarily because of a 17.6% reduction of simple synapses on dendritic spines and almost halving of the symmetric synapses on dendritic shafts. The synaptic density was independent of the age of the recipient, the intracerebral location of the graft, and the survival time. Although the synaptic length of some of the individual synaptic types increased, this did not compensate for the loss of synapses. In the intraocular grafts the synaptic density was lower than in the intracerebral grafts. Despite the reduced synaptic density, which mainly involved two synaptic types, we conclude that grafted dentate granule cells can develop a remarkably normal, ultrastructural synaptic organization even in the absence of major afferent inputs. This outcome must accordingly be achieved by reorganization of the available intrinsic afferents. PMID- 3343390 TI - Ultrastructural organization of normal and transplanted rat fascia dentata: I. A qualitative analysis of intracerebral and intraocular grafts. AB - Few studies have dealt with the general ultrastructure and synaptic organization of grafted brain tissue. This study was therefore performed to extend current light microscopic observations on intracerebral and intraocular grafts of hippocampal tissue to the ultrastructural level. Blocks of tissue containing the hippocampus and fascia dentata from day 21 embryonic rats were grafted into the brain of developing and adult rats and to the anterior eye chamber of adult rats. After 100 or 200 days of survival the recipient rat brains or eyes were processed for electron microscopy. Tissue containing the graft dentate molecular layer and adjacent granule cell layer was selected for ultrastructural analysis, together with a few samples of the hilus and CA3. Normal dentate tissue was analyzed as control. At the light microscopic level most intracerebral and intraocular grafts displayed an organotypic organization with clearly recognizable cell and neuropil layers. Under the electron microscope the grafted granule cells had normal appearing dendrites bearing the normal types of spines and forming the normal types of synapses. This was the case even in the absence of the normal major extrinsic afferents like the perforant path. The graft dentate granule cells formed axons and terminals with characteristics of the normal mossy fiber system in the hilus and CA3, in addition to aberrant supragranular mossy fiber terminals known from light microscopic studies of dentate transplants. Abnormal structures included a few dendritic growth cones and an increased occurrence of polyribosomes in spines. Their occurrence indicates ongoing dendritic plasticity even 100 days after transplantation. There was also an increased density of glial elements, particularly in the intraocular grafts. In some of these grafts the granule cells displayed immature traits in terms of nuclear indentations. Dentate interneurons of the basket cell type were present in both the intracerebral and the intraocular grafts. We conclude that grafted dentate granule cells, in different surroundings and without the normal, major perforant path input, can develop a basically normal cellular morphology, which includes the normal ultrastructural characteristics of the dendrites with spines and synapses, and the mossy fibers and its terminals. PMID- 3343392 TI - Trajectories of regenerating retinal axons in the goldfish tectum: I. A comparison of normal and regenerated axons at late regeneration stages. AB - To visualize and compare the intratectal path of normal and regenerated retinal axons, HRP was applied to localized sites in the dorsotemporal and dorsonasal retina in normal goldfish and in goldfish at 3-12 months after optic nerve section. The anterogradely labeled axons were traced in tectal whole mounts. In normal animals the axons were confined to the appropriate ventral hemitectum. Therein they ran in very orderly routes (Stuermer and Easter: J. Neurosci. 4:1045 1051, '84) and terminated in regions retinotopic to the labeled ganglion cells in the retina. The terminal arbors of dorsotemporal axons resided in the ventrorostral tectum and those of dorsonasal axons in the ventrocaudal tectum. In regenerating animals the terminal arbors also resided at retinotopic regions, where they sometimes formed two separate clusters. In contrast to normal axons, the regenerating ones traveled in abnormal routes through the appropriate and inappropriate hemitectum. From various ectopic positions, they underwent course corrections to redirect their routes toward the retinotopic target region. In their approach toward their target sites, dorsotemporal and dorsonasal axons behaved differently in that the vast majority of dorsotemporal axons coursed over the more rostral tectum whereas dorsonasal axons progressed into the caudal tectal half. This differential behavior of regenerating dorsonasal and dorsotemporal axons was substantiated by a quantitative evaluation of axon numbers and orientations. PMID- 3343393 TI - Trajectories of regenerating retinal axons in the goldfish tectum: II. Exploratory branches and growth cones on axons at early regeneration stages. AB - HRP was applied to small sites in the dorsotemporal or dorsonasal retina in fish at 10-36 days after optic nerve section. The anterogradely labeled axons were visualized in tectal whole mounts. Axons traveled through all regions of the tectum in various abnormal routes. Misrouted axons were also seen to alter their orientation and to direct their course toward their target. At all regeneration stages the majority of dorsotemporal axons coursed and achieved target-related orientations preferentially within the rostral tectal half whereas dorsonasal axons proceeded into the caudal tectum. The growing axons exhibited various morphologies. All axons in the superficial fascicle layer stratum opticum (SO) and some in the synaptic layer stratum fibrosum et griseum superficiale (SFGS) were unbranched and tipped with a leading growth cone. Other axons in the synaptic layer carried one to several growth cones at their ends and often filopodia proximal to the growth cone, or they had sprouted numerous side branches with growth cones and filopodia on the shaft and on branches. Some axons at retinotopic or ectopic sites gave rise to several long branches of several hundred microns in length, with growth cones and filopodia. From 32 days onward axons ending in terminal arbors at retinotopic sites became apparent. Thus, numerous axons at early regeneration stages go through a phase of exploratory growth on their way toward their target sites. PMID- 3343394 TI - Neonatal deafening alters nonpyramidal dendrite orientation in auditory cortex: a computer microscope study in the rabbit. AB - In order to examine the influence of afferent input on nonpyramidal dendrite development in the auditory cortex, unilateral deafening was carried out in neonatal rabbits at birth, approximately 6 days prior to the onset of hearing. Deafening was produced by surgical removal of the incus and stapes ossicles, aspiration of the cochlear perilymph, and kanamycin injection into the oval window. At 60 days of age, acoustic stimulation of the deafened ear was unable to evoke auditory brainstem responses. The brains of experimental and littermate control rabbits were processed according to the Golgi-Cox Nissl method. The dendritic systems of lamina III/IV spine-free nonpyramidal cells in the auditory cortex contralateral to the deafened ear were digitized from 340-micron-thick coronal sections with the aid of a computer microscope. Three-dimensional spatial and statistical analyses revealed that nonpyramidal dendrite length in neonatally deafened rabbits increased 27% relative to littermate controls. A fan-in projection analysis revealed that the increased dendrite length in the deafened animals was maximum in the tangential direction and toward the white matter. Computer rotation of digitized neurons from neonatally deafened rabbits also revealed evidence of abnormal dendritic growth in the form of recurved dendrites. We interpret our results to indicate that unilateral cochlear destruction early in development causes a reorganization of the ascending auditory pathway which extends to the contralateral cerebral cortex. Because the auditory cortex contralateral to the deafened ear still receives acoustic input from the undamaged ipsilateral ear, normal nonpyramidal dendritic growth in the auditory cortex is, in part, dependent upon afferent activity arising from both ears. PMID- 3343395 TI - Morphology and ultrastructure of physiologically identified substantia gelatinosa (lamina II) neurons with axons that terminate in deeper dorsal horn laminae (III V). AB - In order to determine their local circuit function, we have examined physiologically characterized, intracellularly labeled neurons in laminae I and II with light and electron microscopes. Single neurons in the spinal substantia gelatinosa (lamina II) of the cat and monkey were recorded intracellularly and characterized physiologically. Following characterization, the neurons were labeled with horseradish peroxidase that was iontophoretically ejected from the recording micropipette. After fixation and sectioning, histochemical reaction allowed visualization of the neuron soma, dendrites, and axon. The four nociceptive neurons reported here (three from cats and one from a monkey) had axons that distributed terminal collaterals to deeper laminae of the spinal cord, including laminae III, IV, and V. Electron microscopy of the axons demonstrated that the parent axons were myelinated and that the terminal collaterals established synaptic contact with neurons in the deeper laminae. These results suggest that some substantia gelatinosa neurons relay nociceptive information to neurons in deeper regions of the spinal dorsal horn via myelinated axons. PMID- 3343396 TI - Ultrastructural characterization of the synapses of the crossed temporodentate pathway in rats. AB - The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway from the entorhinal cortex to the contralateral dentate gyrus and to compare the synapses of the sparse crossed pathway with those of the massive ipsilateral temporodentate pathway. The synapses of the crossed pathway were identified by using EM degeneration and EM autoradiographic techniques. For the degeneration studies, adult male Sprague-Dawley rats were killed 1, 2, or 4 days following a unilateral entorhinal cortex lesion and prepared for electron microscopy. To identify the synapses by using autoradiographic techniques, four animals received injections of 3H-proline into the entorhinal cortex, were allowed to survive for 3 days, and were prepared for EM autoradiography. Degenerating synapses of the crossed pathway that were found in the molecular layer of the dentate gyrus contralateral to a lesion formed asymmetric synapses on spines and possessed presynaptic organelles indistinguishable from synapses of the ipsilateral temporodentate pathway. The number of degenerating synapses was very low at all survival intervals (14.80 degenerating synapses/10,000 microns2 at 1 day postlesion and 1.95 degenerating synapses/10,000 microns2 at 2 days postlesion); no degenerating synapses were found at 4 days postlesion. Ninety-eight percent of the degenerating synapses found at 1 day postlesion exhibited electron-lucent degeneration. At 2 days postlesion 83% of the degenerating synapses in the dorsal blade and 18% of those in the ventral blade showed lucent degeneration; the remainder were electron dense. EM autoradiography confirmed the degeneration studies in terms of the type of terminals that were labeled and suggested that the density of the crossed pathway was higher than the degeneration results implied. We conclude that synapses of the crossed temporodentate pathway have a similar ultrastructure to synapses of the ipsilateral temporodentate pathway but exhibit a rapid form of degeneration such that they disappear very rapidly following the lesion. PMID- 3343397 TI - The process of reinnervation in the dentate gyrus of adult rats: an ultrastructural study of changes in presynaptic terminals as a result of sprouting. AB - The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway after they had sprouted to reinnervate the dentate gyrus following the destruction of the normal ipsilateral temporodentate pathway. The synapses of the sprouted crossed temporodentate pathway were identified at the EM level by using autoradiographic techniques and by evaluating the degeneration of the pathway following secondary lesions. Both EM autoradiography and EM degeneration revealed that the terminals of the sprouted crossed temporodentate pathway formed asymmetric synapses on spines; individual terminals appeared to make more synaptic contacts per terminal (multiple synapses) than in the case of the normal crossed pathway. In the two lesioned animals exhibiting the best labeling, labeled terminals made an average of 3.0 +/- 2.2 and 2.0 +/- 1.3 contacts per terminal. In contrast, labeled terminals in normal animals exhibited only one contact per terminal. The terminals of the sprouted pathway were also larger than those of the normal crossed pathway. The synapses of the crossed temporodentate pathway that degenerated after a secondary lesion of the entorhinal cortex exhibited both electron-lucent and electron-dense forms of degeneration at 2 days postlesion. In two animals that were quantitatively analyzed, the density of degenerating synaptic terminals was 281 and 218/10,000 microns2 in the terminal field of the sprouted crossed pathway. These values are much higher than in normal animals, where the density of degenerating synaptic terminals was only 2.12/10,000 microns2 at 2 days postlesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343398 TI - Distribution of cells projecting to thalamus vs. those projecting to cerebellum in subdivisions of the dorsal column nuclei in raccoons. AB - To learn the distribution of cells projecting to the thalamus, as opposed to the cerebellum, in the mechanosensory nuclei of the dorsal medulla of raccoons, we analyzed the retrograde transport of horseradish peroxidase from the ventrobasal complex of the thalamus and from the cerebellum. We found six nuclear regions projecting heavily to the thalamus with very small projections to the cerebellum: Bischoff's, central cuneate, central gracile, rostral cuneate, rostral gracile nuclei, and cell group z. Two regions showed heavy projections to the cerebellum with no projections to the thalamus: the lateral portion of the external cuneate nucleus and the compact portion of cell group x. Four regions showed more equivalent projections to both target regions: basal cuneate, medial portion of the external cuneate nucleus, medial tongue extension of the external cuneate nucleus, and reticular portion of cell group x. Three more ventral regions were labeled: lateral cervical nucleus from thalamic injections but not from cerebellar injections; central cervical nucleus from cerebellar injections, which crossed the midline, but not from thalamic injections; and lateral reticular nucleus from both target regions. In most medullary regions, most cells project to one target and very few project to the other; we suggest that the cells projecting to the minor target convey samples of the information going to the major target. PMID- 3343400 TI - Morphology of physiologically identified mitral cells in the carp olfactory bulb: a light microscopic study after intracellular staining with horseradish peroxidase. AB - Physiologically identified mitral cells in the carp olfactory bulb were stained by intracellular injection of horseradish peroxidase in order to study the morphology in detail. The somata were fusiform, elongated, oval, triangular, or irregular. The mean diameters of the somata were 30 microns X 14 microns. Two to five thick dendrites arose from the somata and frequently gave off branches to form glomerular tufts. The dendrites extended less than 400 microns; the dendritic field of single mitral cells in the medial or lateral part of the olfactory bulb was confined within the respective part of the bulb. The axons arose from either the somata or the dendrites and had a conical initial portion, usually with a smooth contour. Some cells had poorly developed intrabulbar axon collaterals. No difference between the mitral cells in the medial part of the olfactory bulb and those in the lateral part was found in the soma diameter, the dendritic diameter at the base, or the number of first-order dendrites. However, there was a difference in the site of the origin of the axon between them: most of the axons of the mitral cells in the medial part arose from the dendrites, while most of the axons of the mitral cells in the lateral part arose from the somata. The morphology of physiologically identified mitral cells is basically consistent with that reported in the Golgi studies of teleosts. The limited dendritic fields of mitral cells may underlie the previously reported functional separation of the olfactory bulb into medial and lateral parts. The results also indicate that the two parts of the teleost olfactory bulb are differentiated not only functionally but also morphologically. PMID- 3343399 TI - Medullary sources of projections to the kinesthetic thalamus in raccoons: external and basal cuneate nuclei and cell groups x and z. AB - In raccoons and other mammals, a pathway for kinesthetic sensation (from muscles, fascia, tendons, and joints) reaches the anterodorsal cap of the ventrobasal thalamus and the anteriormost part of the somatic sensory cerebral cortex. To find the medullary component of this kinesthetic pathway in raccoons, small injections of horseradish peroxidase were made in the thalamus under guidance of simultaneous electrophysiological recording from kinesthetic projections. As determined by retrograde labeling following these injections, kinesthetic thalamic subregions receive projections as follows: caudomedial from cells in the external cuneate nucleus and its medial tongue, rostromedial from cells in basal cuneate nucleus, and rostrolateral from cells in cell group z and the reticular division of cell group x. Electrophysiological recording showed kinesthetic representations in each of these medullary regions. Labeled cells were also observed in the infratrigeminal subnucleus of the lateral reticular nucleus. Cats have kinesthetic projections to the thalamus from the basal cuneate and cell group z; raccoons (and monkeys) have these plus projections from the external cuneate and cell group x. This suggests that the kinesthetic projection system in raccoons and monkeys is expanded in correlation with their more dextrous use of the hand. PMID- 3343401 TI - Synaptic organization of cholinergic amacrine cells in the rhesus monkey retina. AB - In the rhesus monkey retina, choline acetyltransferase (ChAT) immunoreactivity has been used to study the localization and synaptic organization of cholinergic neurons by both light and electron microscopy with peroxidase-antiperoxidase immunohistochemistry. ChAT-containing neurons are a type of amacrine cell with 97.5% of their cell bodies localized to the ganglion cell layer and the remainder in the inner nuclear layer. Their processes arborize in a single narrow band in the inner plexiform layer in a plane dividing the outer two-thirds from the inner one-third of this synaptic region. With electron microscopy, ChAT-immunoreactive amacrine cell processes were observed to be primarily postsynaptic to the diffuse invaginating cone bipolar cells and presynaptic to ganglion cells, although they are both post- and presynaptic to immunohistochemically unlabeled amacrine cell profiles and to ChAT-containing amacrine cell processes as well. PMID- 3343402 TI - Somatotopic organization of the primary sensory trigeminal neurons in the hagfish, Eptatretus burgeri. AB - Primary sensory trigeminal projections were investigated in the hagfish following application of horseradish peroxidase (HRP) to the sensory branches. In our control preparations we were able to distinguish five sensory ganglia and their respective nerves. HRP application confirmed the almost exclusive relation of each of these nerves to their respective ganglia, with very little overlap. In normal frontal sections of the medulla oblongata, five columns of fibers surrounded by neuronal cell bodies could be clearly distinguished, but the number is probably fortuitous, for there was no one-on-one relationship with the five trigeminal ganglia. From their peripheral connections, we surmised that columns 1 and 3 handle general cutaneous sensation, columns 2, 4, and 5 handle taste sensation, and column 5 handles general mucous cutaneous sensation conveyed by utricular ganglion cells. Dorsally located columns received projections from nerves with dorsal peripheral connections, and more ventrally located columns received projections from nerves with ventral peripheral connections. This relation is the reverse of that seen in other vertebrates. PMID- 3343403 TI - Neuronal death and synapse elimination in the olivocerebellar system: III. Cell counts in the inferior olive of developing rats X-irradiated from birth. AB - The change with age of cell number in the developing inferior olivary nucleus (ION) of the normal rat, compared to the time course of the regression of the polyneuronal innervation of Purkinje cells by olivary axons (i.e., the climbing fibers), suggests that the involution of the redundant olivocerebellar contacts is caused by a reduction of axonal branching rather than by degeneration of the parent cells, this being also suggested by the normal size of the olivary population in adult rodents whose Purkinje cells retain polyneuronal innervation. However, the similar size of the adult ION population does not necessarily imply that the development history is the same in normal and multiply innervated adult rodents. Therefore, cell counts were performed in developing rats which had been repeatedly X-irradiated from birth until postnatal day 14 and which retained polyneuronal innervation. The results show that, although less marked than during normal development, the evolution of the ION population is also characterized by a phase of cell loss followed by a slow increase. However, the number of cells in X-irradiated rats is higher than in their controls from birth to postnatal day 15 but becomes identical at 20 days and later. These data confirm that cell death in the ION does not play a major role in the shaping of olivocerebellar connections. PMID- 3343404 TI - Species differences in hippocampal commissural connections: studies in rat, guinea pig, rabbit, and cat. AB - The tritiated amino acid autoradiographic method was employed to characterize the patterns of commissural projections originating in the hippocampus of the rat, guinea pig, rabbit, and cat. The results demonstrate that significant differences between species are present despite the overall similarity of the projections. In the rat and cat the commissural connections are widely distributed along the septotemporal axis of the hippocampus, but in the guinea pig and rabbit they are less widely distributed along this axis. Second, within the hippocampus proper the radial distribution of the commissural projection is species specific. In the rat, CA3 commissural projections are present in both the strata oriens and radiatum, but the densest projection is to the stratum oriens. In the guinea pig the radial distribution of this projection is similar to that observed in the rat, but in the rabbit the projection is almost entirely confined to the stratum oriens. In contrast, in the cat the CA3 commissural projection is very dense to the stratum radiatum and sparse to stratum oriens. An analysis of the relative density of label in the molecular layer of the fascia dentata suggests that the density of the commissural projection from CA4 is much greater in the rat and cat than in the guinea pig or rabbit. These results indicate that care must be exercised in the generalization of connectional data between species. The results also suggest a possible explanation for differences observed in the electrophysiology of these connections between species. PMID- 3343406 TI - The motor nuclei and sensory neurons of the IIIrd, IVth, and VIth cranial nerves in the monitor lizard, Varanus exanthematicus. AB - The motor nuclei of the oculomotor, trochlear, and abducens nerves of the reptile Varanus exanthematicus and the neurons that subserve the sensory innervation of the extraocular muscles were identified and localized by retrograde and anterograde transport of horseradish peroxidase (HRP). The highly differentiated oculomotor nuclear complex, located dorsomedially in the tegmentum of the midbrain, consists of the accessory oculomotor nucleus and the dorsomedial, dorsolateral, intermediate, and ventral subnuclei. The accessory oculomotor nucleus projects ipsilaterally to the ciliary ganglion. The dorsomedial, dorsolateral, and intermediate subnuclei distribute their axons to the ipsilateral orbit, whereas the ventral subnucleus, which innervates the superior rectus muscle, has a bilateral, though predominantly contralateral projection. The trochlear nucleus, which rostrally overlaps the oculomotor nuclear complex, is for the greater part a comma-shaped cell group situated lateral, dorsal, and medial to the medial longitudinal fasciculus. Following HRP application to the trochlear nerve, almost all retrogradely labeled cells were found in the contralateral nucleus. The nuclear complex of the abducens nerve consists of the principal and accessory abducens nuclei, both of which project ipsilaterally. The principal abducens nucleus is located just beneath the fourth ventricle laterally adjacent to the medial longitudinal fasciculus and innervates the posterior rectus muscle. The accessory abducens nucleus has a ventrolateral position in the brainstem in close approximation to the ophthalmic fibers of the descending trigeminal tract. It innervates the retractor bulbi and bursalis muscles. The fibers arising in the accessory abducens muscles form a loop in or just beneath the principal abducens nucleus before they join the abducens nerve root. The afferent fibers conveying sensory information from the extraocular muscles course in the oculomotor nerve and have their perikarya in the ipsilateral trigeminal ganglion, almost exclusively in its ophthalmic portion. PMID- 3343407 TI - Synaptic connections between primary trigeminal afferents and accessory abducens motoneurons in the monitor lizard, Varanus exanthematicus. AB - We studied the anatomical pathway underlying the nictitating reflex in the monitor lizard Varanus exanthematicus by the anterograde degeneration technique combined with retrograde transport of horseradish peroxidase (HRP) and electron microscopy. After application of HRP to the abducens nerve, retrogradely labeled neurons were observed in the ipsilateral principal and accessory abducens motor nuclei. The transection, in the same experiments, of the root of the trigeminal nerve resulted in massive degeneration of myelinated fibers in the descending trigeminal tract. In the ipsilateral accessory abducens nucleus, we observed electron-dense degenerating axon terminals that formed asymmetric synaptic contacts with the primary and secondary dendrites of large neurons retrogradely labeled with HRP. A few of the degenerating terminals could be traced in serial sections to myelinated axons. No terminal degeneration was found in the contralateral accessory abducens nucleus or in the ipsilateral and contralateral principal abducens nuclei. The present results are complementary with the findings of previous light microscopic experimental tracing studies (Barbas Henry, H.A., and A.H.M. Lohman, J. Comp. Neurol. 1986, 254:314-329; see also J. Comp. Neurol. 1988, 267:370-386), and strongly suggest the existence in Varanus of a monosynaptic, unilateral reflex pathway in which trigeminal fibers, presumably originating from the cornea, synapse with motoneurons of the bursalis and retractor bulbi muscles, which are located in the accessory abducens nucleus. This monosynaptic pathway may mediate a rapid unilateral eyeball retraction and nictitating membrane extension. PMID- 3343405 TI - Metamorphosis of identified neurons innervating thoracic neurohemal organs in the blowfly: transformation of cholecystokininlike immunoreactive neurons. AB - With antisera to gastrin/cholecystokinin, we studied the postembryonic development of neurons in the thoracic ganglia of the blowfly Calliphora erythrocephala. There are some changes in the population of thoracico-abdominal neurons displaying gastrin/CCK-like immunoreactivity (CCKLI): some CCKLI neurons cannot be found after pupariation; other neurons become immunoreactive during metamorphosis. Six large thoracic CCKLI neurons could, however, be followed through metamorphosis. These CCKLI neurons innervate neuropil in thoracic ganglia and segmental neurohemal organs in the larva. In the adult insect the same neurons innervate many regions of thoracic neuropil and extensive neurohemal areas dorsally in the fused thoracico-abdominal ganglia. The immunoreactive terminals are located in the neural sheath, and electron microscopy shows that only an extracellular basal lamina separates them from the circulating hemolymph. On the basis of the location of their terminals, it can be suggested that the six CCKLI neurons have functions as neurosecretory cells both in the larva and in the adult. In both developmental stages the neurons can interact with large portions of the thoracic nervous system and release bioactive substance into the circulation. A CCK-like substance may be used both as a transmitter/neuromodulator and as a neurohormone by the same neuron. The larval neurohemal organs are described here for the first time. They show characteristics of thoracic perisympathetic organs known to exist in more primitive insects. The adult neurohemal regions on the other hand are typical of higher insects. Since the neurohemal areas are continuously (during development) innervated by the six large CCKLI neurons, we conclude that the larval neurohemal organs metamorphose into the adult neurohemal area in the neural sheath. PMID- 3343408 TI - Monoclonal antibodies react with neuronal subpopulations in the human nervous system. AB - Monoclonal antibody probes were used to identify antigenic cross reactivities among neuronal subpopulations and to dissect the human nervous system at several levels of organization. Six monoclonal antibodies, prepared with immunogens from Drosophila melanogaster or human nervous tissue, were used to localize antigens immunocytochemically in normal adult human neocortex, hippocampus, cerebellum, spinal cord, and retina. Four of the six antibodies were neural specific in their reactivity and each stained a unique combination of neurons. The antibodies reacted with at least three subpopulations of cerebral cortical neurons, including discrete populations of pyramidal and nonpyramidal cells. Components of a widely distributed functional system within the spinal cord and cerebellum were labelled by one antibody, which reacted with neurons in the nucleus dorsalis of Clarke, deep cerebellar nuclei, and Purkinje cells. At the single-cell level, three of the monoclonals differentially labelled the photoreceptor cell outer segment, inner segment, and perikaryon. Three of the six antibodies were reactive with specific protein bands on immunoblots of tissue homogenates. This monoclonal antibody panel provides a novel and potentially useful method of analysis of the organization of the normal and diseased human nervous system. PMID- 3343409 TI - Tinea of the face caused by Trichophyton rubrum with histologic changes of granuloma faciale. AB - We report a case of tinea of the face caused by Trichophyton rubrum in which the histologic changes were consistent with granuloma faciale. We recommend that local infection with dermatophytes be considered in all cases of histologic granuloma faciale, especially when the clinical presentation is atypical for this dermatosis. PMID- 3343410 TI - Pseudoepitheliomatous, keratotic, micaceous balanitis. A clinical lesion with two histologic subsets: hyperplastic dystrophy and verrucous carcinoma. AB - A 58-year-old man presented with a 4-year history of a slowly enlarging, hyperkeratotic plaque on his glans penis that was compatible with a clinical diagnosis of pseudoepitheliomatous, keratotic, micaceous balanitis. The lesion had been treated unsuccessfully on three occasions with superficial shave excisional biopsies. Complete surgical excision produced excellent cosmetic and functional results with no evidence of recurrence at 3- and 6-month follow-up. A diagnosis of verrucous carcinoma was made on histologic examination of the excised material. Pseudoepitheliomatous, keratotic, micaceous balanitis is a distinctive clinical entity that represents a histologic spectrum ranging from hypertrophic-hyperplastic penile dystrophy to verrucous carcinoma. PMID- 3343412 TI - Ulerythema ophryogenes with multiple congenital anomalies. AB - Ulerythema ophryogenes, a rare dermatologic disorder characterized by inflammatory keratotic facial papules that may result in scars, atrophy, and alopecia, can occur in association with other congenital anomalies. A case reported here was accompanied by an unusual facies, developmental delay, central nervous system abnormalities, dental anomalies, and undescended testes. There was no response of the cutaneous lesions to topical keratolytics, topical tretinoin, or a short course of oral isotretinoin. PMID- 3343411 TI - Basal cell carcinoma arising in a sebaceous nevus during childhood. AB - It is uncommon for malignancy to develop in a sebaceous nevus before puberty. We report a case of basal cell carcinoma arising in a sebaceous nevus during childhood in a normal-appearing lesion. Periodic evaluation to detect malignant degeneration is recommended for children even if removal is encouraged at a future date. PMID- 3343413 TI - Generalized lentiginosis. AB - A patient with generalized lentiginosis and no other associated problems is described. The various syndromes and anomalies associated with generalized lentiginosis are reviewed. Inheritance patterns, long-term prognosis, and recommendations for evaluation and follow-up are discussed. PMID- 3343414 TI - Kaposi's sarcoma occurring in a dermatome previously involved by herpes zoster. AB - A 31-year-old black man with a history of intravenous drug abuse developed a mass in his neck, a biopsy of which revealed Kaposi's sarcoma. The patient underwent radiation therapy, and the mass diminished in size. Approximately 2 months later the patient developed a herpes zoster infection in the left T3 distribution. The vesicular eruption resolved, but postherpetic neuralgia remained. Two months after the herpes zoster infection, the patient developed many small nodules in the area of the prior vesicular eruption. Biopsy revealed these nodules to be Kaposi's sarcoma. At this time no other cutaneous lesions were present. We believe that these nodules represent the occurrence of the Koebner phenomenon in a patient with Kaposi's sarcoma and the acquired immunodeficiency syndrome. PMID- 3343415 TI - Tubuloreticular structures in a papular eruption associated with human immunodeficiency virus disease. AB - A widespread pruritic papular eruption associated with human immunodeficiency virus has been previously described. Electron microscopic study of lesional skin from a patient who presented with such an eruption showed cytoplasmic tubuloreticular structures in every venular capillary endothelial cell that was studied. The significance of this finding and the possible cause of these structures are discussed. This new finding strongly suggests that this dermatosis is a dermatosis related to acquired immunodeficiency syndrome (AIDS) and may be helpful in confirming the diagnosis of the AIDS-related complex or AIDS in future patients presenting with this dermatosis. PMID- 3343417 TI - Incorrect use of the term "cosmetic surgery". PMID- 3343416 TI - CO2 laser and granuloma annulare. PMID- 3343418 TI - Preoperative skin marking. PMID- 3343419 TI - Mohs surgery report: design of an appropriate rhombic flap for a circular defect created by Mohs microscopically controlled surgery. AB - The rhombic flap is a transposition flap based on exact geometric design. The rhombic transposition principle, however, can be applied to circular as well as to geometric wounds. A method is suggested by which the best rhombic flaps for any specific anatomic site can be generated without conversion of the wound to a rhombic design. PMID- 3343420 TI - Stump the experts. A solitary lesion located on the left cheek. PMID- 3343421 TI - Electrosurgery principles: cutting current and cutaneous surgery--Part II. AB - The use of cutting current for electrosurgical excision is a valuable procedure for the cutaneous surgeon. Last month, the basic principles of cutting current were reviewed (J Dermatol Surg Oncol 14:29-31, 1988). This month, Part II will cover the technical aspects of cutting current administration. PMID- 3343422 TI - Credentialing in dermatologic surgery. AB - Dermatologic surgeons' rights to perform surgery are being and will be challenged more and more. Some methods of peer review and credentialing are suggested and the specialty is urged to move ahead with formal planning for more training in the surgical aspects of dermatology. PMID- 3343423 TI - On credentialing. PMID- 3343424 TI - Toward authentic competence. PMID- 3343425 TI - Acute pseudomonas infection of the external ear (malignant external otitis). AB - Pseudomonas aeruginosa commonly causes low-grade infections of the external auditory canal. If these infections are inadequately treated, they can progress into a severe form of external otitis called malignant external otitis (MEO). MEO usually occurs in elderly diabetic patients and demands immediate diagnosis and medical therapy in order to prevent systemic invasion, neurologic sequelae, and even death. We present two cases of acute pseudomonas infections of the ear, neither of which progressed to MEO due to early implementation of antibiotic therapy. PMID- 3343426 TI - Morpheaform basal cell carcinoma in a young black woman. AB - Basal cell carcinomas are uncommon in black patients, and morpheaform basal cell carcinomas are an uncommon histologic subtype. This case report describes the rare occurrence of a morpheaform basal cell carcinoma in a relatively young black patient. This patient underwent Mohs micrographic surgery as the primary therapy for this tumor. Some features of morpheaform basal cell carcinomas are reviewed, and basal cell skin cancer in blacks is discussed. PMID- 3343427 TI - Early effects of inhalation injury on lung mechanics and pulmonary perfusion. AB - We investigated the early effects of a rather large amount of cotton-smoke on lung mechanics and pulmonary perfusion. Under halothane anesthesia 18 ewes were intubated with a double-lumen tube. In 6 sheep the left lung was exposed to smoke, in another 6 the right lung. A sham group of 6 sheep was insufflated with air instead of smoke. Prior to and 30-45 min following the smoking- (sham-) procedure the following parameters were determined for the smoke- (sham-) exposed and the contralateral lung: static compliance, inspiratory airway resistance, and physiologic dead space ratio. In addition MAP, MPAP, WP, and CO were recorded. The data indicate that inhalation of large amounts of smoke has no major direct effects on pulmonary mechanics and perfusion in the early post-injury period. Only an increase in airway resistance of the smoke exposed lungs was found, which must be attributed to a local reflex mechanism. PMID- 3343429 TI - Bacterial colonization and infection in an intensive care unit. AB - One hundred and one patients, nursed in an intensive care unit for at least 24 h, were monitored for bacterial colonization and infection. The infection rates were similar to those in other reports. Patients were not generally colonized with common environmental strains in the unit. Bacterial dissemination between patients was uncommon. No gentamicin resistant gram negative or Staphylococcus aureus strains were observed, nor methicillin resistant Staphylococcus aureus strains. The hypothesis that these favourable conditions are partly related to the excellent isolation and barrier nursing facilities in the unit cannot be fully substantiated. PMID- 3343428 TI - Comparison of non-protected lower respiratory tract secretions and protected specimen brush samples in the diagnosis of pneumonia. AB - The aim of this prospective study was to compare the results obtained with the non-protected lower respiratory tract secretions samples (LRS) with the protected specimen brushes (PSB) performed through a fiberoptic bronchoscope in mechanically ventilated patients, when pneumonia was suspected. The diagnosis of pneumonia was ultimately made at the end of the hospitalisation, in a double blind manner by 2 members of the medical staff not aware of the bacteriologic results of LRS and PSB. LRS and PSB were performed in 24 patients. PSB culture was considered as positive at a level of 10(3) colony-forming units per milliliter (cfu/ml) microorganisms. Twenty-five samples from 24 patients were divided as follows: (1) LRS (-) and PSB (-) 5 samples: the clinical diagnosis of pneumonia was never established. (2) LRS (+) and PSB (+) 10 samples: the clinical diagnosis of pneumonia was always established, 2 microorganisms were involved 4 times and 1 microorganism 6 times. (3) LRS (+) and PSB (-) 10 samples: the clinical diagnosis pneumonia was retained in 3 with the possibility of false negative PSB. We conclude that (1) a negative LRS eliminated the diagnosis of pneumonia without PSB; (2) a positive LRS was not sufficient to diagnose pneumonia since PSB was negative in 50% of all LRS (+) cases; (3) the possibility of a false negative PSB must be kept in mind particularly in patients previously treated with antibiotics; (4) 2 microorganisms may be responsible for the pneumonia if the previously determined, as significant, bacteriological count (greater than or equal to 10(3) cfu/ml) appears to be accurate. PMID- 3343430 TI - Use of the oxygen cost of breathing as an index of weaning ability from mechanical ventilation. AB - The oxygen cost of breathing (which is the difference in oxygen consumption measured during controlled ventilation and again during spontaneous ventilation) was measured in 30 patients between the ages of 17 and 96 years at the time of commencement of weaning from mechanical ventilation. There was a significant exponential correlation between the oxygen cost of breathing in ml/m2/min and the oxygen cost of breathing as a percentage of total oxygen consumption during spontaneous ventilation (OCB/VO2SV%) and the duration of weaning in days. PMID- 3343431 TI - Toe temperature versus transcutaneous oxygen tension monitoring during acute circulatory failure. AB - Measurements of toe temperature and transcutaneous PO2 (PtcO2) have been both suggested for non-invasive assessment of peripheral blood flow in acute circulatory failure. The underlying principle of the two methods is that cutaneous vasoconstriction occurs early when tissue perfusion is altered. In 15 patients, we compared the two measurements during cardiogenic shock (27 measurements) or septic shock (29 measurements). Toe-ambiant temperature gradient and PtcO2 correlated well together (r = 0.66, p less than 0.001) especially in hyperkinetic septic shock (r = 0.79, p less than 0.001). In cardiogenic shock, toe-ambiant temperature correlated well with cardiac index (r = 0.63), stroke index (r = 0.64) and oxygen transport (r = 0.65), and these correlations were stronger than for PtcO2. In septic shock, both techniques were poor indicators of blood flow indexes but PtcO2 rather correlated with arterial pressure (r = 0.66) and left ventricular work (r = 0.66). Trend evaluation of data revealed in cardiogenic shock that the increase in toe temperature usually preceded the increase in PtcO2. Since measurement of PtcO2 is technically more complicated, correlates less well with standard hemodynamic parameters and later reflects cardiovascular improvement, it has no advantage over measurement of toe temperature in circulatory shock. In cardiogenic shock, measurements of toe temperature can reliably track cardiac output changes. In septic states, however, non-invasive assessment of skin perfusion is of limited interest. PMID- 3343433 TI - Acute trichloroethylene poisoning with additional ingestion of ethanol- concentrations of trichloroethylene and its metabolites during hyperventilation therapy. AB - One hour after suicidal ingestion of about 150 g of trichloroethylene, a 32-year old male was admitted to hospital. On admission, the patient's state of consciousness deteriorated from somnolence to coma. Based on blood level data, an absorbed trichloroethylene dose of at least 35 g was estimated. Additionally, ethanol, which is a strong inhibitor of trichloroethylene metabolism, had been ingested. With respect to the high dose of trichloroethylene, hyperventilation therapy was performed for 28 h. Concentrations of trichloroethylene and its metabolites in blood and urine were determined by gas chromatography. Due to hyperventilation and inhibition of trichloroethylene metabolism, not more than 30% of the absorbed dose was metabolized and excreted via kidneys. Under normal respiratory conditions and in the absence of ethanol, this fraction amounts to about 75%. Obviously, hyperventilation and ethanol-induced inhibition of metabolism led to considerably enforced pulmonary elimination of the absorbed trichloroethylene. PMID- 3343432 TI - Detection of overdosage of sedation in a patient with renal failure by the absence of lower oesophageal motility. AB - We report an accidental overdosage of morphine and midazolam in a patient with renal failure receiving haemofiltration detected by the absence of oesophageal motility. This situation demonstrates the difficulties of assessing the level of sedation as well as the dosage requirements in this type of patient. PMID- 3343434 TI - Persistent ST-segment elevation following pericardiocentesis: caution with thrombolytic therapy. AB - We report a case of persistent electrocardiographic ST-elevation following pericardiocentesis despite lack of evidence for transmural infarction or vasospasm. The electrocardiographic pattern was felt to reflect subepicardial injury due to a small myocardial laceration. The implications of this finding are discussed. PMID- 3343435 TI - Hypoglycaemia in salt water near-drowning victims. PMID- 3343436 TI - Vowel processing by a model of the auditory periphery: a comparison to eighth nerve responses. AB - A model of peripheral auditory processing that incorporates processing steps describing the conversion from the acoustic pressure-wave signal at the eardrum to the time course activity in auditory neurons has been developed. It can process arbitrary time domain waveforms and yield the probability of neural firing. The model consists of a concatenation of modules, one for each anatomical section of the periphery. All modules are based on published algorithms and current experimental data, except that the basilar membrane is assumed to be linear. The responses of this model to vowels alone and vowels in noise are compared to neural population responses, as determined by the temporal and average rate response measures of Sachs and Young [J. Acoust. Soc. Am. 66, 470 479, (1979)] and Young and Sachs [J. Acoust. Soc. Am. 66, 1381-1403, (1979)]. Despite the exclusion of nonlinear membrane mechanics, the model accurately predicts the vowel formant representations in the average localized synchronized rate (ALSR) responses and the saturating characteristics of the normalized average rate responses in quiet. When vowels are presented in background noise, the modeled ALSR responses are less robust than the neural data. PMID- 3343437 TI - Interpreting measures of frequency selectivity: is forward masking special? AB - In a previous article [Lutfi, J. Acoust. Soc. Am. 76, 1045-1050 (1984)], the following relation was used to predict measures of frequency selectivity obtained in forward masking from measures obtained in simultaneous masking: F(g) = G + H(g) - H(0), where, for a given masker level, F is the amount of forward masking (in dB) as a function of signal-masker frequency separation (g), H is the amount of simultaneous masking, and G is the amount of forward masking for g = 0. In the present study, the relation was tested for a wider range of signal and masker frequencies, masker levels, and signal delays. The relation described thresholds from all conditions well with the inclusion of one free parameter lambda corresponding to a constant frequency increment, F(g) = G + H(g + lambda) - H(lambda). The parameter lambda was required to account for observed shifts in the frequency of maximum forward masking. It is argued that a single tuning mechanism can account for commonly observed differences between simultaneous- and forward-masked measures of frequency selectivity. PMID- 3343438 TI - Frequency selectivity in loudness adaptation and auditory fatigue. AB - An intermittent monaural tone may induce a decline in the loudness of a continuous tone presented to the same ear [Canevet et al., Br. J. Audiol. 17, 49 57 (1983)]. Two experiments studied the frequency selectivity of loudness adaptation induced in this manner. The method of successive magnitude estimations was used to measure the loudness of a monaural 84-s test tone before and after a single presentation of a 24-s inducer tone in the same ear. The first experiment shows that, for an inducing tone (500, 1000, or 3000 Hz) approximately 15 dB more intense than a test tone set to one of 21 different frequencies, adaptation is greatest when the two tones have the same frequency; with increasing difference between the test-tone and inducer frequencies, adaptation progressively declines. The second experiment measured frequency selectivity in the loudness reduction caused by a 1000-Hz inducer as a function of its level. As inducer level went from 75 to 95 dB (with test tone constant at 60 phons), selectivity passes progressively from the type seen in short-term or low-level fatigue (maximal for the 1000-Hz test tone) to a type seen in long-term or high-level fatigue (maximal for the 1000-Hz test tone) to a type seen in long-term or high-level fatigue (maximal at frequencies higher than that of the inducer or fatiguing tone). A common cochlear origin and a continuity between the mechanisms of ipsilaterally induced adaptation and high-level fatigue are suggested by the data. PMID- 3343439 TI - Modeling sensorineural hearing loss. I. Model and retrospective evaluation. AB - The present article describes an approach to the evaluation of psychoacoustic data from the hearing impaired. The results obtained from the hearing impaired in several studies of frequency resolution, temporal resolution, and speech recognition are compared to the results expected for noise-masked normal listeners. It is presumed in this approach that the hypothetical noise-masked normal listeners have masked thresholds that agree perfectly with the quiet thresholds of the hearing-impaired subjects. Using this approach, most of the results obtained from impaired ears on spectral-resolution and speech-recognition tasks could be accurately predicted, an exception being results from spectral resolution paradigms using fixed-level signals. Some of the data from hearing impaired listeners on temporal-resolution tasks, on the other hand, could not be adequately described with this approach. The latter data, however, were much more limited. Additional data are needed to better evaluate the adequacy of this approach in describing the performance of the hearing impaired on temporal resolution tasks. PMID- 3343440 TI - Intensity-time tradeoff for constant hearing loss with high sound levels. AB - The tradeoff relation between exposure intensity and duration for constant hearing loss was investigated in two series of experiments using Mongolian gerbils. The gerbils were exposed to a 1/3 octave band of noise at 2.5 kHz. In the first series animals were exposed to 120 dB SPL for 1 h, to 126 dB SPL for 15 min, and to 126 dB SPL for 3.75 min. In the second series, shorter durations were used: 120 dB SPL for 15 min, 126 dB SPL for 3.75 min, and 126 dB SPL for 56 s. The hearing thresholds were determined behaviorally immediately before exposure and 6 weeks after exposure. The results suggest that the intensity-time tradeoff for the investigated intensity interval is between 1.5 and 3 dB per halving of the duration. PMID- 3343441 TI - Compensating for a bite block in /s/ and /t/ production: palatographic, acoustic, and perceptual data. AB - Electropalatography was used to monitor linguapalatal contact patterns in /s/ and /t/. Talkers often compensated incompletely for a bite block, both immediately after its insertion (sample B1) and after 10 min of practice (sample B2). Significant differences in the number of sensors contacted were noted between normal and bite-block samples for both /s/ and /t/. Differences in length of constriction in /t/, and the A-P location and width of the groove in /s/ were also noted. The two native English subjects compensated better than three Arabic subjects, perhaps because English /s/ and /t/ are formed more posteriorily and with a smaller contact area than their Arabic counterparts. A significant correlation existed between the area and A-P location of linguapalatal contact. All five subjects formed a groove for /s/ in sample B2, but two often did not produce /t/ with complete constriction. This suggests a groove is critical for /s/, but complete constriction is not critical for /t/. The contact patterns in sample B2 more closely resembled normal speech than those in sample B1 in some instances, while in other instances the reverse was true. The conclusion that subjects sometimes overcompensated in sample B2 was supported by the results of detailed acoustic and perceptual analyses for one subject. Taken together, the results suggest that compensation for a bite block is not instantaneous, and that specific parameter values may be encoded in central phonetic representations. PMID- 3343442 TI - Differences in fricative production between children and adults: evidence from an acoustic analysis of /sh/ and /s/. AB - Speech samples of 12 speakers (8 children and 4 adults) producing the fricatives /s/ and/sh/ followed by the vowels /i/ and /u/ were analyzed to locate the major spectral prominences. Results showed that the fricative low-frequency prominences for children's samples differed from those of adults in three important ways: (1) They were generally higher in frequency; (2) they were greater in amplitude relative to higher frequency regions; and (3) they showed greater effects of vowel context. The first finding can be explained by a simple scaling of adult models of fricative production to accommodate children's smaller vocal tracts. The other two findings suggest, however, that there are other anatomical and articulatory differences between children and adults affecting fricative production. The data presented here suggest that one important difference may be the relative sizes of the fricative constriction and the glottal opening. PMID- 3343443 TI - Perception of the [m]-[n] distinction in VC syllables. AB - This study complements earlier experiments on the perception of the [m]-[n] distinction in CV syllables [B. H. Repp, J. Acoust. Soc. Am. 79, 1987-1999 (1986); B. H. Repp, J. Acoust. Soc. Am. 82, 1525-1538 (1987)]. Six talkers produced VC syllables consisting of [m] or [n] preceded by [i, a, u]. In listening experiments, these syllables were truncated from the beginning and/or from the end, or waveform portions surrounding the point of closure were replaced with noise, so as to map out the distribution of the place of articulation information for consonant perception. These manipulations revealed that the vocalic formant transitions alone conveyed about as much place of articulation information as did the nasal murmur alone, and both signal portions were about as informative in VC as in CV syllables. Nevertheless, full VC syllables were less accurately identified than full CV syllables, especially in female speech. The reason for this was hypothesized to be the relative absence of a salient spectral change between the vowel and the murmur in VC syllables. This hypothesis was supported by the relative ineffectiveness of two additional manipulations meant to disrupt the perception of relational spectral information (channel separation or temporal separation of vowel and murmur) and by subjects' poor identification scores for brief excerpts including the point of maximal spectral change. While, in CV syllables, the abrupt spectral change from the murmur to the vowel provides important additional place of articulation information, for VC syllables it seems as if the format transitions in the vowel and the murmur spectrum functioned as independent cues. PMID- 3343444 TI - Sentence reception in noise from one versus two sources: effects of aging and hearing loss. AB - Sentence reception thresholds (SRTs) and babble detection thresholds (BDTs) were measured for signals presented from loudspeakers located at 0 deg and 90 deg azimuth. In addition, the S/B ratios necessary to achieve SRT in the presence of a 12-talker babble were determined under three conditions in which the speech and babble were presented from the same or spatially separated loudspeakers. In the first experiment, normal-hearing subjects were tested on two occasions. The results were highly reliable, with standard errors of the test-retest differences of less than 1dB for all conditions. In the second experiment, SRTs, BDTs, and S/B ratios were measured for three normal-hearing groups (less than or equal to 39, 40-54, and greater than or equal to 55 years) and for a fourth group with presbycusis (greater than or equal to 55 years). Presbycusics had higher SRTs and BDTs than all other groups regardless of age, and the oldest normals had higher thresholds than younger subjects. Presbycusics required higher S/B ratios than any of the normal groups, and the oldest normal group needed a higher S/B ratio compared to the youngest group. All groups demonstrated a significant advantage in S/B ratio when the sentences and babble sources were spatially separated compared to when they were presented from the same loudspeaker. There was no significant difference in the magnitude of advantage due to spatial separation of speech and noise between the normal groups regardless of age, but the presbycusics had significantly smaller advantages than all normals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343445 TI - Measurement of pitch by subharmonic summation. AB - In order to account for the phenomenon of virtual pitch, various theories assume implicitly or explicitly that each spectral component introduces a series of subharmonics. The spectral-compression method for pitch determination can be viewed as a direct implementation of this principle. The widespread application of this principle in pitch determination is, however, impeded by numerical problems with respect to accuracy and computational efficiency. A modified algorithm is described that solves these problems. Its performance is tested for normal speech and "telephone" speech, i.e., speech high-pass filtered at 300 Hz. The algorithm out-performs the harmonic-sieve method for pitch determination, while its computational requirements are about the same. The algorithm is described in terms of nonlinear system theory, i.c., subharmonic summation. It is argued that the favorable performance of the subharmonic-summation algorithm stems from its corresponding more closely with current pitch-perception theories than does the harmonic sieve. PMID- 3343447 TI - Cochannel speech separation. AB - The multisignal minimum-cross-entropy spectral analysis (multisignal MCESA) is applied to the problem of separating the speech signals of two talkers speaking simultaneously on a single channel, e.g., when two talkers use a single microphone. A new two-stage approach to the problem is proposed in which a spectral separator is followed by a spectral tailoring procedure. The spectral separator produces an initial estimate of the speech spectrum for each talker. Then the spectral tailoring procedure employs the multisignal MCESA technique to adjust the initial spectral estimates to account for the characteristics of the known cochannel composite speech signal. The research emphasis is placed on the implementation and evaluation of the spectral tailoring procedure, i.e., the use of the multisignal MCESA in the proposed scheme. Its usefulness is evaluated and validated by listening tests and by comparing the spectral distortions of the estimated voices before and after the multisignal MCESA processing. PMID- 3343446 TI - Use of syllable-scale timing to discriminate words. AB - Assuming that only primitive, imperfect phonetic labeling of speech could be achieved by an automatic speech segmenter, words from several small vocabularies were identified using discriminant analysis, where the locations of prominent acoustic boundaries were combined in the optimum linear fashion. A set of two syllable words that shared the same spelling in a weak alphabet (using categories like stop closure, fricative, vowel, etc.), but that differed in such features as which syllable was stressed, the tensity of the vowel, the identity of particular segments, etc., was selected. Discriminant analysis on the vector of six segmental boundaries achieved recognition accuracy 6.3 times better than chance. The words were produced by six talkers at two speaking tempos and measured by hand from sound spectrograms. Testing was performed on productions different from those used in training. When more confusable words (sharing the same stress pattern) were employed, performance was still five times better than chance. In a third experiment, the first two word sets were combined, and a subset of the variables (four of them) shared in common was employed for identification. This time recognition using temporal information was still able to do a reasonable job of discriminating the words. The results suggest that considerable information is available in segmental timing for identifying words even when the phonetic labeling of speech is weak. PMID- 3343448 TI - Processing of acoustic signals in the auditory system of bony fish. AB - In order to determine unambiguously the bearing of a sound source, a fish must be able to resolve acoustic pressure and the components of the acoustic displacement vector from the signals detected by the otolithic organs. A new hypothesis for the processing of acoustical information by bony fish is presented. It is demonstrated that much of the processing required to do this may be implicit in the structure of the ear and its associated neural innervation. Possible algorithms are presented that the central nervous system might use to further process the derived information to localize a sound source and discriminate frequency and range. The hypothesis is shown to be consistent with much of what is known of the morphology and physiology of the auditory system of bony fishes. PMID- 3343449 TI - Lateralization and sequential relationships in the octave illusion. AB - Subjects made lateralization judgments concerning sequences of dichotic chords whose components stood in octave relation. In condition 1, each ear received a sequence consisting of 400- and 800-Hz tones in alternation, such that when one ear received the 400-Hz tone, the other ear simultaneously received the 800-Hz tone. Condition 2 was identical to condition 1, except that the alternating tones were at 600 and 1200 Hz instead. In condition 3, dichotic chords at 400 and 800 Hz alternated with dichotic chords at 600 and 1200 Hz. In all conditions, the amplitude relationships between the higher and lower tones were varied, and the percent lateralization to the higher frequency signal was plotted as a function of these amplitude relationships. In all conditions, when the tones at the two ears were equal in amplitude, lateralization tended to be toward the ear receiving the higher frequency signal. Averaged across subjects, this tendency in condition 1 was overcome only when the lower frequency signal was 12 dB higher in amplitude, and, in condition 2, when it was 9 dB higher. However, in condition 3, the tendency was overcome when the lower frequency signal was 3 dB higher in amplitude. The lateralization effect was thus shown to be influenced by the sequential relationships between the frequencies presented to the two ears. PMID- 3343450 TI - The role of glycogen and phosphate in ultrasonic attenuation of liver. AB - The excess ultrasonic attenuation caused by adding glycogen and inorganic phosphate to liver homogenates has been studied to determine the underlying differences between attenuation coefficients of normal and diffusely diseased livers. Results show that glycogen has a higher than average specific absorption coefficient compared to other large molecular weight biomolecules. Since the glycogen content of liver can vary from 1%-10% of wet weight, this compound may have a major time-varying effect on the liver ultrasonic attenuation coefficient, even in normal subjects. In contrast, the excess attenuation of liver homogenate resulting from addition of inorganic phosphate was not significant at presumed physiological levels. The implications of these findings are discussed relative to tissue characterization efforts based on in vivo measurements of ultrasonic attenuation coefficients of liver. PMID- 3343451 TI - Late clinical outcome in patients with early ventricular fibrillation after myocardial infarction. AB - Whether ventricular fibrillation occurring within 48 h after acute myocardial infarction is associated with particular clinical features and poor prognosis, especially in patients with anterior myocardial infarction, is still debated. Therefore, clinical variables and in-hospital and 1 year mortality rates were analyzed in 2,088 patients, aged 18 to 95 years (mean +/- SD 64 +/- 12), admitted to the hospital with acute myocardial infarction between 1979 and mid 1984. One hundred forty-seven patients (7%) had at least one episode of ventricular fibrillation occurring within 48 h of hospital admission. Of these, 25% died during their initial hospitalization compared with 13% of patients without early ventricular fibrillation (p less than 0.001). In greater than 50% of patients with early ventricular fibrillation, the immediate cause of death was left ventricular failure or cardiogenic shock. In contrast, the 1 year mortality rate after hospital discharge was not significantly greater in patients with than in those without early ventricular fibrillation (15 versus 11%, respectively), particularly in the subgroup of patients with anterior myocardial infarction in which the mortality rate tended to be lower in patients with early ventricular fibrillation (8 versus 14%, respectively). Similar mortality results were found when only primary (not associated with left ventricular failure) ventricular fibrillation was analyzed. The left ventricular ejection fraction and the incidence of complex ventricular arrhythmias from 24 h ambulatory electrocardiographic monitoring obtained at hospital discharge were not different in survivors with or without early ventricular fibrillation (0.45 +/- 0.13 versus 0.49 +/- 0.14 and 41 versus 41%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343452 TI - Circulating cardiac myosin light chains in patients with angina at rest: identification of a high risk subgroup. AB - To detect myocardial cell damage, serum samples of 42 consecutive patients with angina at rest were screened for cardiac myosin light chains, which were detected in 22 patients (52%). In 17 of these patients there was a persistent release of myosin light chains lasting until the 4th hospital day, whereas in 7 patients myosin light chains were only detectable during the initial 24 h after admission. The presence of myosin light chains correlated with signs of ischemia in the electrocardiogram (ECG) (p less than 0.05) and with the extent of coronary artery narrowing (p less than 0.05). Cardiac myosin light chains were elevated in serum only if there was a greater than or equal to 75% diameter narrowing in at least one major vessel. In all five patients who developed transmural myocardial infarction during the course of their hospital stay, myosin light chains were detectable greater than or equal to 28 h before the diagnosis of myocardial infarction could be established by ECG criteria and conventional serum enzymes. Thus the detection of circulating cardiac myosin light chains enables one to identify a subgroup of patients with angina at rest having more severe coronary artery disease with a worse outcome. PMID- 3343453 TI - Maximal exercise testing and gas exchange in patients with chronic atrial fibrillation. AB - To evaluate the response of patients with chronic atrial fibrillation to exercise, 50 men (mean age 65 +/- 8 years) with atrial fibrillation underwent a maximal exercise test using respiratory gas exchange techniques. Patients were classified by the presence (n = 29) or absence ("lone atrial fibrillation," n = 21) of underlying heart disease. Responses were evaluated at a standard submaximal work load (3.0 mph, [4.8 km/h] 0% grade), at the gas exchange anaerobic threshold and at maximal exercise. For all 50 patients, the mean maximal oxygen uptake was 20.6 ml/kg per min, which approximates 85% of the aerobic capacity predicted for age-matched normal individuals. Patients with lone atrial fibrillation demonstrated normal exercise capacity in contrast to patients with atrial fibrillation and known heart disease (22.7 +/- 5 versus 19.1 +/- 5.0 ml/kg per min, p less than 0.05). The mean maximal heart rate (176 +/- 30 beats/min) was approximately 20 beats/min higher than that expected for age, was extremely variable and accounted for only 8% of the variance in maximal oxygen uptake. Maximal heart rate in subjects with lone atrial fibrillation was higher than that of subjects with atrial fibrillation and known heart disease (189 +/- 32 versus 166 +/- 24 beats/min, p less than 0.01). Stepwise regression analysis revealed that maximal systolic blood pressure accounted for 19% of the variance in maximal oxygen uptake (VO2 max), suggesting that systolic function is an important determinant of exercise performance in atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343454 TI - Subthreshold atrial pacing in patients with a left-sided accessory pathway: an effective new method for terminating reciprocating tachycardia. AB - This study investigated the possibility of terminating reciprocating atrioventricular (AV) tachycardia using subthreshold atrial pacing. Ten patients with a left-sided accessory pathway and sustained AV tachycardia underwent subthreshold atrial pacing from the coronary sinus site closest to insertion of the accessory pathway. In seven of these patients, the tachycardia could be reliably terminated with subthreshold atrial overdrive pacing. When pacing at a cycle length of 80 +/- 23% of the tachycardia cycle length, the minimal subthreshold current that was effective in tachycardia termination was 64 +/- 14% of threshold current and the maximal ineffective current was 49 +/- 17% of threshold (p less than 0.05). In all cases, the tachycardia was terminated by one or two instances of atrial capture that resulted in a premature atrial impulse (20 +/- 4% advancement of the atrial cycle) that blocked the AV node limb of the tachycardia. Anterograde conduction over the accessory pathway never occurred, either during the tachycardia or during subthreshold pacing after a return to normal sinus rhythm. No instances of atrial fibrillation were provoked by subthreshold pacing. Possible explanations for the intermittent atrial capture with critically placed subthreshold impulses include supernormal atrial conduction or summation of impulses at the atrial insertion site of the accessory pathway. It is concluded that subthreshold pacing is effective in selected patients with AV tachycardia due to an accessory pathway. Furthermore, because neither atrial fibrillation nor anterograde conduction over the accessory pathway is seen with subthreshold pacing, this modality may hold significant promise for permanent antitachycardia pacing in these patients. PMID- 3343455 TI - Incidence of reentry with an excitable gap in ventricular tachycardia: a prospective evaluation utilizing transient entrainment. AB - The demonstration of transient entrainment has been proposed as evidence of reentry, with an excitable gap as the probable mechanism of tachycardia. A prospective series of 27 consecutive patients with sustained ventricular tachycardia induced by programmed electrical stimulation was studied to determine the frequency with which transient entrainment can be demonstrated and to define the optimal location of pacing and recording electrodes. In all patients, electrodes for pacing and recording were placed in both the left and right ventricles during electrophysiologic study. Among the 19 patients in whom the response to rapid pacing could be evaluated (25 episodes of ventricular tachycardia), transient entrainment was demonstrated in 79% (76% of episodes). Ten of 12 episodes of ventricular tachycardia with a left bundle branch block QRS configuration in lead V1 and 9 of 13 episodes with a right bundle branch block QRS configuration could be transiently entrained (p = NS). Transient entrainment was demonstrated for 8 of 11 episodes of ventricular tachycardia with a left bundle branch block configuration during pacing from the left ventricle, but for only 2 of 10 episodes during pacing from the right ventricular apex (p less than 0.05). Conversely, 9 of 13 episodes of ventricular tachycardia with a right bundle branch block configuration were transiently entrained during pacing from the right ventricular apex, but 0 of 10 episodes were transiently entrained by left ventricular pacing (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343456 TI - "Atrial paralysis": does it explain the irregular ventricular rate during atrial fibrillation? PMID- 3343457 TI - Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia. AB - The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium. PMID- 3343458 TI - Sonospirometry: a new method for noninvasive estimation of mean right atrial pressure based on two-dimensional echographic measurements of the inferior vena cava during measured inspiration. AB - A noninvasive method of estimating mean right atrial pressure would be useful in evaluating hemodynamics and calculating pulmonary pressures by Doppler echocardiography. An electronic pressure gauge was built and tested for measurement of inspiratory pressures during two-dimensional echocardiography to quantitate the diameter of the inferior vena cava. Thirty-one studies were made in 27 alert, informed, consenting patients with an in-place pulmonary artery catheter having right atrial ports. Inferior vena cava diameter was measured in successive 10 mm segments distal to the right atrial-inferior vena cava junction on images obtained while the patient suspended breathing at full inspiration and during each 4 mm Hg increment of a calibrated inspiratory maneuver. Results show that the segment between 5 and 30 mm distal to the right atrial-inferior vena cava junction was the region most responsive to increasing inspiratory pressure. In this segment, the inspiratory pressure required to decrease the inferior vena cava diameter to greater than or equal to 85% of the difference between its maximal (suspended full inspiration) and minimal (over the entire inspiratory maneuver) values was similar or equal to the mean right atrial pressure (measured from the pulmonary artery catheter) (r = 0.87, SEE = 2.9 mm Hg). Minimal inferior vena cava diameter was directly related to mean right atrial pressure (r = 0.56); the minimal to maximal inferior vena cava diameter ratio was inversely related to mean right atrial pressure (r = -0.57). Maximal inferior vena cava diameter and the absolute (measured) amount of inferior vena cava diameter decrease correlated weakly with mean right atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343460 TI - Doppler echocardiography in cardiac tamponade: exaggerated respiratory variation in transvalvular blood flow velocity integrals. AB - Pulsed Doppler echocardiography has been used previously to demonstrate marked changes in transvalvular blood flow velocities during cardiac tamponade in laboratory animals and a small number of patients. To further assess the respiratory changes in transvalvular blood flow during tamponade, pulsed Doppler tracings of flow velocity profiles across all four cardiac valves were recorded during inspiration and expiration in 13 patients during cardiac tamponade, in 6 of the 13 patients after relief of tamponade by pericardiocentesis and in 8 normal control subjects. Flow velocity integrals were calculated for each valve during inspiration and expiration. In the setting of cardiac tamponade, inspiration caused an 85 +/- 46% increase in the flow velocity integral across the pulmonary valve, an 81 +/- 34% increase across the tricuspid valve, a 33 +/- 13% decrease across the aortic valve and a 35 +/- 8% decrease across the mitral valve. These phasic respiratory changes were markedly reduced after relief of tamponade (p less than 0.05 compared with tamponade) and were observed to only a minimal extent in the normal individuals (p less than 0.01 compared with tamponade). The exaggerated respiratory variations in transvalvular flow velocity integrals suggest that Doppler evaluation may be a valuable tool in the diagnosis of cardiac tamponade. Transmitral Doppler indexes of left ventricular filling during cardiac tamponade revealed that inspiration caused a shift to increased filling during late diastole, with a greater contribution of atrial systole to total left ventricular filling. These Doppler indexes did not vary significantly with respiration in the group studied after relief of tamponade or in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343459 TI - Echocardiographic visualization of coronary artery anatomy in the adult. AB - In the light of technologic advances and the development of new imaging planes, the feasibility of two-dimensional echocardiographic visualization of coronary artery anatomy was reevaluated in the adult. Thirty-five subjects were studied using an ultrasonograph equipped with a 3.5 and 5.0 MHz annular array transducer, digital processing and cine loop review. There were 18 normal subjects and 17 patients with heart disease, including 9 patients with valvular, 5 patients with coronary, 2 patients with congenital and 1 patient with cardiomyopathic disease. The mean age was 47 +/- 18 years (range 17 to 79). Modifications of standard parasternal and apical views permitted high quality images of portions of each of the major epicardial vessels adequate for assessment of luminal diameter. The left main coronary artery was seen in 30 (86%) of the 35 subjects and its bifurcation was seen in 15. The left anterior descending coronary artery was seen in 30 subjects (mean length 3.9 +/- 2.3 cm, maximal length 7.5), the left circumflex artery in 11 (1.1 +/- 1.0, maximal 3.0) and the right coronary artery in 32 (5.6 +/- 2.6, maximal 12). Proximal and mid portions of the left anterior descending artery were seen in 23 and 11 subjects, respectively. The average proximal length visualized was 4.2 cm, and the average luminal diameter visualized was 4.9 mm. The average length of the mid left anterior descending coronary artery seen was 1.9 cm and the average luminal diameter seen was 4.6 mm. The proximal right coronary artery was seen in 17 subjects (average visualized length 2.7 cm and average diameter 3.1 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343461 TI - Observer variability in the quantitation of Doppler color flow jet areas for mitral and aortic regurgitation. AB - Early studies using Doppler color flow imaging have suggested that measurement of the regurgitant jet area provides information regarding the severity of valvular insufficiency. This study was performed to assess the observer variability of mitral and aortic regurgitant jet area measurements using the Doppler color technique. Color Doppler recordings from 45 patients were reviewed: 23 patients had aortic regurgitation and 22 had mitral regurgitation. To assess interobserver variability, the largest definable mitral regurgitant jets from three cardiac cycles were independently chosen and measured by planimetry by two observers who were unaware of other patient information. Measurements were repeated by both observers at a separate time to obtain intraobserver data. Videotapes from 23 patients with aortic regurgitation were similarly analyzed. Each observer measured the isovolumic aortic jet (before mitral valve opening) and the maximal aortic regurgitant jet (at any time during diastole) using computer-assisted planimetry. Both intraobserver and interobserver correlations were excellent for mitral regurgitant jet areas (r = 0.97 and r = 0.93, respectively). The intraobserver correlation for isovolumic aortic regurgitant jet was r = 0.73; the interobserver correlation for this measurement was only fair (r = 0.57). For the maximal aortic regurgitant jet area, intraobserver correlation was good (r = 0.86) and interobserver correlation was fair (r = 0.72). These findings suggest that intraobserver and interobserver reproducibility are acceptable for the measurement of mitral regurgitant jet area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343463 TI - Sequential pulse defibrillation in humans: orthogonal sequential pulse defibrillation with epicardial electrodes. AB - A newly described sequential pulse technique, using four mesh electrodes positioned to approximate a true orthogonal system around the heart, was compared with a single pulse system using two of these same electrodes, which were located in positions that would be used for an automatic implantable defibrillator. The influence of electrode size was also assessed. The minimal energy necessary for defibrillation (defibrillation threshold) was determined intraoperatively in 21 volunteer patients undergoing accessory pathway ablation of Wolff-Parkinson-White syndrome. Ventricular fibrillation was induced with alternating current. Ten seconds after fibrillation onset defibrillation shocks were begun using either the single or the sequential pulse technique with stored voltage incremented until defibrillation was accomplished (defibrillation threshold). Selection of the use of a single or sequential pulse technique for the initial attempt was randomized. Defibrillation thresholds were determined in three groups of patients: 1) those with four small mesh electrodes (6 cm2), 2) those with two small and two large (13 cm2) mesh electrodes, and 3) those with four large mesh electrodes. In all cases, the average minimal energy needed for sequential pulse defibrillation was less than that required for single pulse defibrillation in the same patients with the same electrodes (four small, 24.8 +/- 24.7 J single versus 6.7 +/- 8.3 J sequential; two small plus two large, 11.4 +/- 15.0 J single versus 2.7 +/- 1.4 J sequential; four large, 8.1 +/- 5.3 J single versus 3.9 +/- 2.6 J sequential). Using the 6 cm2 electrodes for single pulse defibrillation energies delivered at greater than 45 J in two patients failed to defibrillate the heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343462 TI - Safety and diagnostic accuracy of dipyridamole-thallium imaging in the elderly. AB - The noninvasive diagnosis of coronary artery disease in the elderly can occasionally be difficult. Intravenous dipyridamole-thallium imaging is a potentially useful diagnostic test to determine presence and severity of coronary disease; however, the safety of the procedure has not been determined in an older population. The side effect profile and frequency of severe ischemic responses after 0.56 mg/kg of intravenous dipyridamole were compared in 101 patients greater than or equal to 70 years old and 236 patients less than 70 years old. There were no side effects in 64% and 62% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). Among the 337 patients tested, there were no complications of myocardial infarction or death. The most common cardiac side effect was chest pain, which occurred in 21 (21%) of the 101 patients aged greater than or equal to 70 years and in 64 (27%) of the 236 patients less than 70 years (p = NS). Aminophylline was required to reverse cardiac or noncardiac side effects in 15 (15%) and 36 (15%) of the patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). A severe ischemic response occurred in 2% and 2.5% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). The sensitivity of intravenous dipyridamole-thallium imaging for obstructive coronary artery disease was 86% (25 of 29) and 83% (68 of 82) in older and younger patients, respectively (p = NS); the specificity was 75% (6 of 8) and 70% (16 of 23), respectively (p = NS). Thus, intravenous dipyridamole-thallium imaging is a safe noninvasive method for assessment of older patients with obstructive coronary disease; its side effect profile and diagnostic accuracy are similar to those seen in younger patients. The technique is associated with severe ischemic responses in only a small minority of patients. PMID- 3343464 TI - A new rhythm library for testing automatic external defibrillators: performance of three devices. AB - A library of arrhythmias obtained from patients with cardiac arrest was developed. Such a data base will permit both in vitro testing of the rhythm analysis system of automatic external defibrillators before clinical field trials are conducted and comparison of devices. Defibrillators equipped with voice/electrocardiographic tape recorders and used in the prehospital defibrillation programs in Iowa and King County, Washington provided the rhythm source. From these recordings, segments of ventricular fibrillation with minimal artifact and a duration of greater than or equal to 6 s were selected. Segments of ventricular fibrillation (n = 102) were categorized by average peak amplitude as fine (1 to less than 3 mm), medium (3 to less than 7 mm), coarse (7 to less than 12 mm) and extra coarse (greater than or equal to 12 mm), and transcribed onto high fidelity videocassette tapes. Nonventricular fibrillation cardiac arrest rhythms (n = 144), which included wide complex idioventricular rhythms, ventricular and supraventricular tachycardias, asystole and artifact, were also transcribed. Automatic external defibrillators developed by three manufacturers reached a treat (shock) decision on 88 to 93% of the ventricular fibrillation rhythms and on 5 to 10% of the nonventricular fibrillation rhythms. The latter decisions were defined as false positive, though for many rapid nonventricular fibrillation rhythms, countershock may be the appropriate treatment response. There were no statistically significant differences among the three devices in the shock/no shock decisions. A variety of ventricular fibrillation arrhythmias and terminology to express the preclinical performance of automatic external defibrillators are defined. Three commercially available automatic external defibrillators appear to successfully identify ventricular fibrillation and nonventricular fibrillation rhythms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343465 TI - Spontaneous and electrically induced ventricular arrhythmias during acute ischemia superimposed on 2 week old canine myocardial infarction. AB - The arrhythmogenic effect of acute reversible myocardial ischemia before and 2 weeks after experimental myocardial infarction was investigated in 37 dogs that underwent reversible 10 min occlusion of the first major marginal branch of the left circumflex coronary artery. Subsequently, 24 of the dogs underwent experimental myocardial infarction with permanent left anterior descending coronary ligation, and 13 dogs served as sham-operated controls. Two weeks later, an open chest programmed electrical stimulation was performed in the 13 sham operated and 24 postinfarction dogs to determine its accuracy in predicting the ventricular arrhythmias that develop during a subsequent episode of acute reversible ischemia. After programmed electrical stimulation, the left circumflex marginal branch was reversibly occluded for 10 min at the same site. The incidence of spontaneous ventricular fibrillation during reversible left circumflex marginal coronary occlusion did not differ from the first to the second study in sham-operated dogs, whereas in the postinfarction dogs, it increased from 13% before infarction to 54% after infarction (p = 0.005). The outcome of programmed electrical stimulation predicted spontaneous ventricular arrhythmias during coronary occlusion in only 21% of the postinfarction dogs. The accuracy of programmed electrical stimulation was 42% and its predictive value was 47% in detecting the dogs with spontaneous ventricular fibrillation. Regional myocardial blood flow measurements by microsphere technique identified the severity of reversible ischemia in the infarct border and periinfarction zones as a correlate of spontaneous ventricular fibrillation during coronary occlusion. In contrast, total infarct size correlated with electrically induced but not with spontaneous ventricular arrhythmias. PMID- 3343466 TI - Variable arginine vasopressin levels in neonatal congestive heart failure. AB - Arginine vasopressin levels in 17 neonates with cardiac disease were compared with control levels in 10 healthy newborn infants. Infants with congestive heart failure who were free of left ventricular outflow tract obstruction had a mean level of 80 +/- 18 pg/ml, which was significantly greater than the mean control level (p less than 0.001). Infants with congestive heart failure and left ventricular outflow tract obstruction had a mean vasopressin level of 3 +/- 0.7 pg/ml, which was lower than the mean control level of 6 +/- 0.7 pg/ml (p less than 0.05). The data suggest that impaired forward flow to high pressure sinoaortic and ventricular baroreceptors is necessary for vasopressin release in congestive heart failure. In left ventricular outflow tract obstruction with heart failure these receptors may be impaired or absent, leading to decreased vasopressin release. Low plasma arginine vasopressin may adversely affect circulatory homeostasis. PMID- 3343469 TI - Retrograde left ventricular flow during early relaxation. PMID- 3343467 TI - Comparison of the cardiac output and stroke volume response to upright exercise in children with valvular and subvalvular aortic stenosis. AB - Cardiac output and stroke volume were evaluated in 17 children (mean age 11.5 +/- 3 years) with discrete, membranous subvalvular (Group I, n = 7) and valvular (Group II, n = 10) aortic stenosis during submaximal and maximal (greater than 75% predicted maximal oxygen consumption) upright cycle ergometry. Patients with valvular aortic stenosis were further subdivided on the basis of their aortic valve gradient at rest determined by cardiac catheterization (Group IIA, gradient less than 40 mm Hg; Group IIB, gradient greater than or equal to 40 mm Hg). These patients were matched with 17 control subjects on the basis of age, sex, height and intensity of exercise during maximal exertion. Cardiac and stroke indexes were determined by the acetylene rebreathing method at each exercise level. Stroke volume index in Group I was significantly greater at rest when compared with that in control subjects (69 +/- 13 versus 53 +/- 11 ml/m2, alpha = 0.01, p less than 0.05) and that in patients in Group II (69 +/- 13 versus 47 +/- 12 ml/m2, alpha = 0.01, p less than 0.05). Patients with subvalvular aortic stenosis were unable to increase their stroke volume index from rest to submaximal exercise and also decreased their stroke volume index at maximal exercise levels. In contrast, patients with mild valvular aortic stenosis (Group IIA) displayed a normal exercise response. Patients with severe valvular aortic stenosis (Group IIB) had a blunted stroke volume response at rest and at each level of exercise, as well as signs of myocardial ischemia (ST segment depression) during maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343468 TI - Noninvasive Doppler color flow mapping for detection of anomalous origin of the left coronary artery from the pulmonary artery and for evaluation of surgical repair. AB - Anomalous origin of the left coronary artery from the pulmonary artery is a rare but important cause of congestive heart failure in infancy and of sudden death at all ages. Diagnosis is often missed when based solely on physical examination and noninvasive methods. A 4 year old patient is presented in whom mitral regurgitation was noted by a referring physician and an anomalous left coronary artery was found by Doppler color flow mapping upon referral and verified at cardiac catheterization. Doppler color flow mapping was also used intraoperatively using a gas-sterilized transducer to further clarify the hemodynamics and assess the surgical result. After creation of an intrapulmonary artery tunnel from the ostium of the left coronary artery to the aorta, anterograde coronary artery flow and absence of a residual left to right pulmonary artery shunt were verified during surgery by Doppler flow mapping. Postoperatively, residual mitral regurgitation and patency of the left coronary artery graft have been followed up serially by Doppler flow mapping. Therefore, Doppler color flow mapping is useful in the diagnosis and intraoperative and postoperative management of this important and potentially life-threatening abnormality. PMID- 3343471 TI - Doppler echocardiographic appearance of cusp tears in tissue valve prostheses. PMID- 3343470 TI - Problems in nomenclature: bulboventricular foramen versus ventricular septal defect. PMID- 3343472 TI - Standardized ECG examination. PMID- 3343473 TI - Nutritional support of the chronically ill elderly female at risk for elective or urgent surgery. AB - Among the elderly, those at highest risk are the chronically ill, inactive patients. Assessing macronutrient requirements and outcome depends on longitudinal studies. Seven chronically ill, elderly female patients suffering from persistent infections, were studied monthly, over a 6-month period to determine their protein and energy requirements. Calorie and protein requirements were based on clinical status. The results of the nutrition support program were monitored using: weight change, nitrogen balance, serum albumin levels, alterations in anthropometric measurements (triceps skinfold thickness and arm muscle circumference), and immune function tests. Based on the 6-month study period data, the calculated mean energy requirement for weight maintenance was 98% of calculated basal energy expenditure (BEE) and the mean protein required for nitrogen balance, 0.8 g/kg desired body weight (DBW). Excess caloric administration resulted in weight gain, determined to be fat (and/or fluid) but not lean body mass. When surgery is contemplated, there should be a 30% (factorial) increase over these base-line values. It is inadvisable to allow elderly patients to sustain any starvation, period given their inability to produce increases in body cell mass even in this 6-month period. PMID- 3343474 TI - Effects of feeding selenium deficient diets to rhesus monkeys (Macaca Mulatta). AB - Pregnant rhesus monkeys (Macaca mulatta) were fed either selenium (Se) deficient or Se supplemented diets with adequate vitamin E. Except for some cardiac irregularities in the first babies born to these females, no physiological disorders due to Se deficiency were seen in a subsequent offspring. Plasma and erythrocyte glutathione peroxidase activities and blood Se levels increased in the Se supplemented monkeys but decreased in the deficient ones. The data indicated that hair Se levels reflect long term exposure to this element. In a very preliminary experiment, evidence was obtained to indicate that dietary protein deficiency along with Se deficiency will generate cardiomyopathic lesions characteristic of Se deficiency. It is hypothesized that, in addition to Se deficiency, another dietary deficiency (or abnormality) is necessary to produce Se deficiency lesions in higher primates. Higher glutathione transferase (or non Se glutathione peroxidase) activity in tissues of rhesus monkeys may account for this resistance. PMID- 3343475 TI - Magnesium therapy in premature neonates with apnea neonatorum. AB - Apnea, bradycardia, and neuromuscular hyperirritability have been associated with magnesium (Mg) deficiency in young human infants and weanling animals. This is a retrospective review of a clinical experience of Mg therapy among 200 premature neonates who showed physical and clinical chemical changes compatible with Mg deficiency. The 200 infants all had idiopathic apnea neonatorum, and 93% also had the respiratory distress syndrome (RDS). This review was conducted to learn whether Mg therapy was associated with a significant reduction in apnea. The author suggested that the dose of Mg be 0.4 mEq/kg body weight/day, as 50% MgSO4.7H2O intramuscularly (IM) for 5 days; or as 1.0 mEq/kg/day, as 10% MgCl2.6H2O by mouth for 2 or more weeks, with appropriate monitoring of plasma Mg values in all infants. Sixty-one infants received a minimum of 5 days of Mg by either route (mean, 11.4 +/- 0.9, Group A); five received 3-4 doses IM (mean, 3.6 +/- 0.2, Group B); and 134 received 0-2 doses IM (0.5 +/- 0.1, Group C). Group A infants Mg-treated before Day 20 showed earlier cessation of apnea and bradycardia than those treated after Day 20. In Group A patients, 7 dose-days [corrected] of Mg therapy was associated with continuation of apnea; 14 dose-days [corrected], with cessation of apnea. Compared with Group A, Group C continued to develop apnea (P less than .003) and bradycardia (P less than 0.03) over longer periods of time. Group A infants showed no record of death or of hospital readmission for recurrent apnea, while 32 of 134 Group C infants had one or both of those unfavorable outcomes (P less than 0.001), with four of the five deaths in Group C (NS) as the sudden infant death syndrome (SIDS). In conclusion, Mg was associated with a reduction of apnea in this population. Emphasis was placed on the need to closely observe infants receiving supplementary Mg, with monitoring of plasma Mg levels. PMID- 3343476 TI - Evaluation of zinc status in subjects with Crohn's disease. AB - Zinc status was evaluated in 30 subjects with Crohn's disease. Intestinal resection had previously been performed in 23 of the subjects. The concentrations of zinc were determined in plasma, erythrocytes, percutaneous muscle biopsies, and in urine collected during 24 hours. The results were compared with those in 19 healthy controls. Most of the patients had a normal zinc status. The levels of zinc were, however, reduced (i.e., less than mean -2 SD for controls) in plasma for five, in erythrocytes for two, and in muscle biopsies for six subjects with Crohn's disease. The mean concentrations of zinc in plasma and erythrocytes were reduced (P less than 0.05), whereas the mean content of zinc in muscle biopsies and the mean urinary excretion of zinc were not significantly different, in subjects with Crohn's disease. The various zinc parameters did not correlate to each other. The results indicate that some subjects with Crohn's disease had an intracellular zinc depletion, which, however, was not reflected by a reduction in levels of zinc in plasma. PMID- 3343477 TI - Red cell transketolase studies in a private practice specializing in nutritional correction. AB - Erythrocyte transketolase (TKA) and thiamin pyrophosphate percentage uptake, or effect (TPPE) were performed on 1011 patients between 1983 and 1986. The subjects were drawn from a private practice specializing in nutritional correction as a major therapeutic thrust. Either TKA or TPPE or both were abnormal in 283 (28%). Out of the total number of patients with these abnormal studies 36 have been selected as representative. Their clinical presentation is correlated with subsequent laboratory testing in order to draw attention to the practical value of the test in a clinical setting. These data are presented because of the surprisingly high incidence of abnormal tests, that strongly suggests that there is widespread marginal nutritional deficiency in the United States and that it represents a clinical problem that deserves far more attention than it is presently receiving. PMID- 3343478 TI - The impact of body composition on the regulation of lipolysis during short-term fasting. AB - Lipolytic rates were determined in normal-weight young adult (low body fat), normal-weight elderly (moderate body fat), and obese young adult (high body fat) subjects after an overnight (12-15 hr) and short-term (60-87 hr) fasting period. A simultaneous infusion of [1-13C] palmitate acid and [2H5]glycerol was used to measure the inflow of palmitate and glycerol into the bloodstream, and H2 18O dilution was used to measure body composition. The amount of body fat differed between the young adult (11 kg), elderly (23 kg) and obese (49 kg) subjects. Total lean body mass was similar in the normal-weight young adult (60 kg) and obese (63 kg) groups, but was lower in the elderly (46 kg). Lipolytic rates per unit of fat mass decreased in each group relative to the increase in the amount of body fat. Lipolytic rates, expressed as a function of lean body mass, however, were the same in all three groups. These results suggest that body composition contributes to the regulation of lipolysis during fasting. The decreased rate of lipolysis in subjects who have excess body fat may reflect the decreased need, per unit fat mass, for lipolysis to meet the energy requirements of the lean body mass. PMID- 3343479 TI - Industry support for optometry. PMID- 3343480 TI - Capitation and the transfer of risk in new health delivery systems. PMID- 3343481 TI - Comprehensive vision screening program: Illinois' approach. AB - This article discusses a statewide vision screening program that utilizes trained and certified vision screening technicians under the auspices of the Department of Public Health. Public Act 81-174, the Child Vision and Hearing Test Act, mandates periodic vision screening of children using accepted and approved instruments and standards. The program receives consultation from the Children's Vision Services Advisory Committee, consisting of optometrists, ophthalmologists and others in health and education programs. Topics addressed include: training and certification of technicians; screening, referral and follow-up; program summary of statewide screening statistics of 1.2 million children for fiscal year 1985, etc. PMID- 3343483 TI - Rapid, inexpensive confirmation of chlamydial infection. AB - This article will hopefully make all optometrists aware of a rapid, direct method for confirming a diagnosis of chlamydial (inclusion) conjunctivitis. The Micro Trak test from Syva is inexpensive, highly specific, and very sensitive for all human serovars of Chlamydia trachomatis. The current regimens for chlamydial conjunctivitis are also described. PMID- 3343482 TI - Hepatitis B virus in human tears: ocular examination of an asymptomatic carrier. AB - The hepatitis B virus or Dane particle has been linked to hepatocellular carcinoma and is a major cause of chronic liver disease. Hepatitis B virus is found in blood and many body fluids including human tears. A 31-year-old White male was inadvertently discovered to have chronic active hepatitis secondary to a hepatitis B infection, during an autoimmune disorder work-up for recurrent episcleritis. It was also discovered that two of the patient's family members had developed chronic disease from the virus. Optometrists should be aware of the serious implications of this disease and take the proper precautions when examining hepatitis patients so that the possible risk of contracting infection through contaminated tears will be reduced. PMID- 3343485 TI - Optometry and the public health. PMID- 3343484 TI - A philosophy for marketing independent practice. PMID- 3343486 TI - Optometry, professionalism and public health: some notes on identity and survival. PMID- 3343487 TI - A conceptual model for CNS practice. PMID- 3343488 TI - Adult rehabilitation: attitudes and implications. PMID- 3343489 TI - Improving safety for hospitalized elderly. PMID- 3343490 TI - Therapeutic use of self. PMID- 3343491 TI - Determinants of quality nursing care. PMID- 3343492 TI - Disruptive behaviors. PMID- 3343493 TI - Neural tube defects. PMID- 3343494 TI - Corn oil ketogenic diet for children with intractable seizures. AB - The ketogenic diet is a well-established, but relatively infrequently used, therapy for intractable seizures in children. Currently, the standard ketogenic diet is formulated using medium chain triglyceride (MCT) oil as its major caloric source. Cost, availability, and gastrointestinal side effects limit its use in some cases. We report the successful substitution of corn oil for MCT oil in six children treated with the ketogenic diet for intractable seizures. In each case, the corn oil ketogenic diet was effective, well-tolerated by the patient and parents, and free of clinical toxicity. Corn oil also has the major advantages of being much less expensive and more available that MCT oil. Its use in the ketogenic diet appears to be effective, safe, and practical. PMID- 3343495 TI - Neuropsychological effects of childhood cancer treatment. AB - The potential neuropsychological effects of treatment were investigated in 124 childhood cancer patients. Children were classified into groups on the basis of treatment modality and treatment status. All patients received systemic chemotherapy. Other treatment modalities included intrathecal chemotherapy and intrathecal chemotherapy plus central nervous system radiation therapy. Treatment status was determined by whether children were newly diagnosed patients in active treatment or long-term survivors of cancer. This classification resulted in five groups; group 1 (n = 29)--children with newly diagnosed disease who were receiving intrathecal chemotherapy; group 2 (n = 21)--children with newly diagnosed disease who were receiving systemic chemotherapy without central nervous system treatment; group 3 (n = 24)--long-term survivors who had received intrathecal chemotherapy; group 4 (n = 25)--long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy; and group 5 (n = 25)--long term survivors who had received systemic chemotherapy only (no specific central nervous system treatment). Groups were compared by using multivariate analysis of variance on sets of neuropsychological test variables that represent major cognitive domains. Results of comparisons indicated significant group differences for most dependent-variable sets. Follow-up pairwise comparisons showed that the group of long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy consistently obtained lower test scores than the other four groups. These findings are consistent with results of previous studies, thus indicating that intrathecal chemotherapy plus cranial radiotherapy is associated with significant effects on neuropsychological performance. Comparisons among newly diagnosed and long-term groups of patients who did not receive cranial radiotherapy yielded null results on measures of higher-order cognitive functions. However, significant group differences were observed on measures of fine-motor and visual-motor skills; newly diagnosed groups obtained lower scores than the nonirradiated long-term survivor groups. Findings were attributed to chemotherapy-induced peripheral neuropathy that differentially affected the newly diagnosed groups. PMID- 3343496 TI - A prospective study of neuropsychological sequelae in children with brain tumors. AB - Surgery and radiotherapy are the primary modalities of treatment for pediatric brain tumors. Despite the widespread use of these treatments, little is known of their acute effects (within one year posttreatment) on neuropsychological functions. An understanding of acute treatment effects may provide valuable feedback to neurosurgeons and a baseline against which delayed sequelae may be evaluated. This study compares pre- and posttherapy neuropsychological test performance of pediatric brain tumor patients categorized into two groups on the basis of treatment modalities: surgery (n = 7) and radiotherapy (n = 7). Treatment groups were composed of children aged 56 to 196 months at the time of evaluation with heterogeneous tumor diagnoses and locations. Comparisons of pretherapy findings with normative values using confidence intervals indicated that both groups performed within the average range on most measures. Outstanding deficits at baseline were observed on tests of fine-motor, psychomotor, and timed language skills, and are likely to be attributable to tumor-related effects. Comparisons of pre- versus posttherapy neuropsychological test findings indicated no significant interval changes for either group. Results suggest that surgery and radiotherapy are not associated with acute effects on neuropsychological functions. PMID- 3343498 TI - Skin entry site swabbing a poor predictor of catheter-related sepsis. PMID- 3343497 TI - The value of guided needle muscle biopsy. PMID- 3343499 TI - Infection risk in the bearded patient. PMID- 3343500 TI - Nosocomial pneumonia: new concepts on an old disease. PMID- 3343501 TI - Stress ulcer prophylaxis and ventilation pneumonia: prevention by antibacterial cytoprotective agents? AB - The gastric and tracheal flora of 142 consecutive patients receiving stress ulcer prophylaxis were investigated, identifying identical isolates by typing. Furthermore, the growth pattern of normal respiratory bacteria and organisms causing ventilation pneumonia at different pH values and the in vitro effect of sucralfate and bismuth subsalicylate on these bacteria in simulated gastric fluid were studied. The results obtained were as follows: (1) with rising gastric pH bacterial counts in gastric aspirates, especially gram-negatives, increased significantly; (2) in 45 (31.7%) of the patients identical organisms were first isolated in gastric samples and one to two days later in tracheal secretions; (3) ventilation pneumonia was significantly more frequent in patients with high gastric pH; (4) pathogens causing ventilation pneumonia grew well in simulated gastric fluid at higher pH values, unlike normal respiratory organisms; and (5) sucralfate and bismuth subsalicylate showed antibacterial activity against frequent causative organisms of ventilation pneumonia. PMID- 3343502 TI - Evaluation of a urinary catheter with a preconnected closed drainage bag. AB - The incidence of bacteriuria, significant urinary tract infection, and cost associated with the use of two urinary catheter drainage systems were evaluated in a population of hospitalized adult males. A commercially available device comprised of a Foley catheter attached with a heat-shrunk plastic seal to the tubing of a closed drainage bag (preconnected system) was compared with a standard system that had the Foley catheter attached to the closed drainage bag after it had been inserted. Using a randomized prospective design, the performance of the preconnected system in 97 patients was compared with that of the standard system in 105 patients. Catheters were left in place a mean of 6.4 and 7.6 days in the respective groups. Bacteriuria occurred after catheter insertion in 11.3% of patients receiving the preconnected system and 13.3% of patients receiving the standard system (not statistically significant). When bacteriuria developed, it occurred within seven days of catheter insertion in 50% of instances, irrespective of drainage system employed, suggesting that manipulations related to catheter insertion were important in initiating bacteriuria. Significant urinary tract infections occurred in only 2% of all patients studied. The higher cost for purchasing the preconnected system was not warranted for the population of patients studied. PMID- 3343503 TI - Shock in the pediatric patient. PMID- 3343504 TI - Cavitary infiltrate in an immunosuppressed patient. Invasive pulmonary aspergillosis. PMID- 3343506 TI - Physician's liability for failure to consult with and/or refer a patient to a specialist. PMID- 3343505 TI - Fallopian hydatidiform mole: a case report. PMID- 3343507 TI - Quantitative histochemical determination of Na+ and K+ in microscopic samples using carbon furnace atomic absorption spectrometry. AB - Carbon furnace atomic absorption spectrometry was used to measure the Na and K content of freeze-dried microscopic tissue samples. This method was sufficiently sensitive to measure pmol amounts of Na and K from tissue weighing 10-60 ng. Within the spatial resolution of the microdissection procedure, ion diffusion that might occur during cryosectioning, freeze-drying, and dissection of the tissue did not seem to be a problem. Data obtained with this methodology were in agreement with previously reported values of the Na and K content of various tissues, thus supporting the usefulness of this quantitative histochemical technique. PMID- 3343508 TI - Localization of high benzaldehyde dehydrogenase activity in rat upper gastrointestinal tract mucosa: a quantitative histochemical study. AB - An unusual aldehyde dehydrogenase (AlDH) phenotype, histochemically similar to the "tumor-associated" AlDH appearing during rat hepatocarcinogenesis, was detected in normal rat upper gastrointestinal tract tissues. This phenotype is characterized by high activities with aromatic substrates, i.e., benzaldehyde (Bz) and NADP. Frozen sections of GI tract tissue from normal rats and from liver nodules induced by a Solt-Farber protocol were evaluated for AlDH activity. A sensitive, high-resolution procedure was used in which sections are pre-incubated in nitroblue tetrazolium and then incubated at 20 degrees C in a viscous polyvinyl alcohol medium containing buffer, phenazine methosulfate, sodium azide, substrate, co-enzyme, and nitroblue tetrazolium. Incubation at a suboptimal pH of 7.0 was found to improve retention of the final reaction product and the linearity with time. Activity was quantitated by computer-assisted microscopic photometry. Intense BzDH-NADP activity was localized in the squamous epithelium of the tongue, esophagus, and fore-stomach, and in the glandular pit cells of the glandular stomach; this activity was not evident in the submucosa, muscle walls, and vessels. Little if any BzDH-NADP activity was observed in the small or large intestine, pancreas, and liver. AlDH in upper GI tissues and in liver nodules shared three characteristics: a sharp localization; a preference for Bz and NADP compared to the aliphatic substrate acetaldehyde and NAD; and a high co-enzyme independent activity in the presence of Bz. PMID- 3343509 TI - Immunocytochemical localization of urate oxidase, fatty acyl-CoA oxidase, and catalase in bovine kidney peroxisomes. AB - We investigated the localization of urate oxidase, peroxisomal fatty acyl-CoA oxidase, and catalase in bovine kidney by immunoblot analysis and protein A-gold immunocytochemistry, using the respective polyclonal monospecific antibodies raised against the enzymes purified from rat liver. By immunoblot analysis, these three proteins were detected in bovine kidney and bovine liver homogenates. Subcellular localization of these three enzymes in kidney was ascertained by protein A-gold immunocytochemical staining of Lowicryl K4M-embedded tissue. Peroxisomes in bovine kidney cortical epithelium possessed crystalloid cores or nucleoids, which were found to be the exclusive sites of urate oxidase localization. The limiting membrane, the marginal plate, and the matrix of renal peroxisomes were negative for urate oxidase staining. In contrast, catalase and fatty acyl-CoA oxidase were found in the peroxisome matrix. These results demonstrate that, unlike rat kidney peroxisomes which lack urate oxidase, peroxisomes of bovine kidney contain this enzyme as well as peroxisomal fatty acyl-CoA oxidase. PMID- 3343510 TI - Carbodiimide as a tissue fixative in histamine immunohistochemistry and its application in developmental neurobiology. AB - The object of this study was to develop an immunohistochemical method that could be used to study neuronal histamine, especially in nerve fibers and terminals where most previous methods have not been applicable. Three new antisera were produced in rabbits against conjugated histamine, and the fixative used in conjugation, 1-ethyl-3(3-diamethylaminopropyl)-carbodiimide (EDCDI), was used in tissue fixation and compared to paraformaldehyde. Specificity of the antisera was established with dot-blot tests on nitrocellulose, with blocking controls and affinity-purified antibodies. EDCDI appeared to be superior to paraformaldehyde as a fixative, and histamine-immunoreactive nerve cells were visualized in developing rat brain during late fetal development from embryonal day 12. By the second postnatal week, the distribution of histamine-immunoreactive neurons in rat brain had reached the adult pattern and immunoreactive nerve fibers were seen in many areas. Posterior hypothalamic neurons from newborn rat in vitro showed strong immunoreactivity for histamine and developed long varicose fibers, which covered the culture dish by the end of the fourth week in vitro. Fixation with EDCDI also allowed detection of histamine in gastric enterochromaffin-like cells and mast cells in rat. The results suggest that the histamine-containing neuron system in rat brain develops during the late fetal and early postnatal periods, and that immunoreactive neurons develop long fibers both in vivo and in vitro. PMID- 3343511 TI - A novel guinea pig macrophage-specific polymorphic molecule. II. Biochemical analysis of the polymorphism. AB - We have identified a macrophage-specific molecule, termed gp98, which has a m.w. of 98,000, is encoded by a gene not linked to the guinea pig lymphocyte antigen complex, is highly immunogenic, and displays a serologic polymorphism among several inbred guinea pig strains. The gp98 molecule was biochemically analyzed to identify a basis for the serologically detected polymorphism. The molecule was demonstrated to be a glycoprotein containing N-linked oligosaccharides. The strain 2 serologic variant, gp98-2, migrated with an apparent m.w. approximately 2500 more than did the strain 13 variant gp98-13. This differential migration was observed in a (strain 2 X strain 13) F1 animal, and persisted after neuraminidase and endoglycosidase F treatment, and after reduction. Trypsin and endoproteinase Lys-C digestion localized the biochemical basis of the polymorphism to the peptide portion of the molecule. Biochemical analysis of the gp98 molecules from five different inbred strains indicated that only two biochemical variants correlating with the serologic variants existed among the five strains. PMID- 3343512 TI - Electrostatic properties of cryoimmunoglobulins. AB - Inhibition of the cryoprecipitation of cryoimmunoglobulins by neutral salts suggests that intermolecular electrostatic (charge-charge) interactions are responsible for their abnormal solution properties. To test this hypothesis, H+ titration curves and isoelectric points were measured for two monoclonal IgG cryoglobulins (Ger and Muk) and compared with four normal (cold soluble) monoclonal IgG. The cryoglobulin Ger manifested values outside the range encountered for the other proteins. The partitioning of the IgG proteins was also examined in aqueous polyethylene glycol-dextran two-phase systems in the presence of both positive and negative salt-induced electrostatic potentials across the phase interface. Both cryoglobulins were found to behave as if they were more negatively charged than the noncryoglobulins. The experiments support the hypothesis that the differences in solubility behavior of monoclonal cryoglobulin and noncryoglobulin proteins are caused by differences in the electrostatic properties of the proteins. PMID- 3343513 TI - Regulation of synthesis of macrophage adhesion molecule, a heterodimeric membrane glycoprotein. AB - Macrophage adhesion molecule is a surface molecule of guinea pig macrophages and neutrophils. It is the counterpart of mouse Mac-1 and human CD11b/CD18 (Mol/OKM 1/Mac-1/Leu-CAM) and is member of a family of heterodimer glycoproteins with a common beta-subunit. Macrophage adhesion molecule is a prevalent molecule in nonactivated macrophages, but it is dramatically decreased in macrophages activated in vivo. The experimental system of activated vs nonactivated guinea pig peritoneal macrophages was used to examine the mechanisms that down-regulate synthesis of this heterodimer molecule. [35S]Methionine labeling of nonactivated macrophages and chase incubation revealed that synthesis involves separate translation of the alpha- and beta-glycopeptides of "high mannose"-containing monomeric precursors, then refolding/assembly to form a heterodimer, and, finally, a maturation process that includes conversion of carbohydrate to "complex" units. Two lines of evidence demonstrate that down-regulation in activated macrophages occurs via restriction of the alpha-species. First, pre beta is detected at 3 h only in activated macrophages. Second, the amount of newly translated pre-alpha averaged 16% in activated macrophages relative to nonactivated macrophages, which is close to the value of 12% for the mature heterodimer. The amount of newly translated pre-beta averaged 62%. These findings identify the regulatory step as a restriction of the alpha-species at, or before, translation. A model is proposed to explain regulation of synthesis of heterodimer membrane glycoproteins. PMID- 3343514 TI - Quantitation of elastin in human urine and rat pleural mesothelial cell matrix by a sensitive avidin-biotin ELISA for desmosine. AB - A specific enzyme-linked immunosorbent assay (ELISA) was developed for the determination of desmosine, a cross-linked amino acid specific to fibrous elastin. Competition between solid phase-bound desmosine-protein conjugate and free desmosine for binding to monospecific anti-desmosine antiserum constituted the underlying principle of the assay. The conjugation of desmosine to different protein carriers was carried out with the 1-ethyl-3-(dimethylamino propyl)carbodiimide (ECDI); rabbits were immunized with desmosine-bovine serum albumin and micro-titer plates were coated with desmosine-egg albumin. An avidin biotin peroxidase system was used to reveal anti-desmosine antibodies bound to the desmosine-protein conjugate. As both conjugates revealed new non-specific common epitopes on the carrier proteins, prior absorption of the anti-desmosine antiserum on rabbit albumin polymerized with ECDI was required to remove the antibodies directed against these neo-antigens. The absorption procedure resulted in an increased specificity and sensitivity. Values ranging from 0.07 to 4 ng of desmosine/well could be detected and this sensitivity was greater than that obtained in previous immunoassays for desmosine. In order to assess the specificity of the test, samples containing aminoacids and urine hydrolysates were included in an assay. Some cross-reactivity was observed with the desmosine precursor lysinonorleucine and the desmosine isomer isodesmosine but, in contrast the very low cross-reactivity observed with collagen hydrolysate was similar to that exhibited by albumin hydrolysate. Analysis of urine samples from 118 normal male volunteers showed, firstly, that urinary creatinine measurement was a good indicator of the amount of urine which could be safely introduced in the assay without risk of non-specific interference by other organic compounds and, secondly, that the desmosine/creatinine ratio was a reliable index for an in vivo assessment of degraded elastin excretion. The assay also allowed quantitation of elastin fiber biosynthesis in the connective tissue matrix of cultured rat pleural mesothelial cells. This ELISA for demosine is a simple technique which should be useful for further in vivo or in vitro investigations of fibrous elastin tissue metabolism. PMID- 3343515 TI - Hazards of the limiting-dilution method of cloning hybridomas. AB - Three hybridoma clones, which were shown to change the characteristics of their antibody specificities when grown under different culturing conditions, are described in detail. This phenomenon was shown to be due to the persistence of mixed clones, even under conditions where standard statistical treatment indicated a high probability of monoclonality. Such mixed clones persisted, sometimes undetected, through repeated cycles of re-cloning. It was shown that the assumption that every viable clone has the same random chance of monoclonality, is invalid, and can lead to misleadingly high estimates for the probability of monoclonality. Verification of seeding of individual wells with single cells is recommended and the relative merits of this versus repeated limiting-dilution cloning are discussed. PMID- 3343516 TI - Evaluation of monoclonality of cell lines from sequential dilution assays. Part II. AB - We extend the analysis in Koziol et al. (J. Immunol. Methods (1987) 105, 139) for the determination of the probability of achieving monoclonality in limiting dilution assays to three or more cloning stages. We also provide a computer program which will carry out this analysis for an arbitrary number of stages. PMID- 3343517 TI - Reaction to the letter: Is that what you mean? PMID- 3343518 TI - Establishment of human Ig producing heterohybridomas by fusion of mouse myeloma cells with human lymphocytes derived from peripheral blood, bone marrow, spleen, lymph node, and synovial fluid. Effect of polyclonal prestimulation and cryopreservation. AB - 50 fusion experiments were carried out to analyse heterohybridization efficiencies on mouse myeloma cells of the P3 X63 Ag8/653 line with human lymphocytes derived from peripheral blood, bone marrow, lymph node, spleen or synovial fluid. We found higher yields of growing and human Ig-producing hybridoma lines when lymphocytes from spleen or lymph node were fused. Although primary hybridomas could be established from fusions with bone marrow-derived cells, only in nine out of 1616 initially seeded wells was Ig production registered. Four fusions using immune cells from synovial fluid were made without success. Independently of the source of lymphocytes pokeweed mitogen (PWM) prestimulation had no enhancing effect on the percentage of wells with cell growth and this did not alter the IgM:IgG ratio in primary hybridomas (9:1), although cells from all compartments used here (with the exception of bone marrow cells) could be stimulated with PWM to produce both IgG and IgM in cultures. Cryopreserved lymphocytes from different sources could be used for fusions with comparable results registered for the fresh material. PMID- 3343519 TI - Natural killer function in flow cytometry. I. Evaluation of NK lytic activity on K562 cell line. AB - Flow cytometry has been employed to establish an NK assay using the K562 target cell line. These cells show a perpendicular light scatter (PLS) characteristically different from lymphocytes. Other physical parameters, such as forward light scatter (FLS), do not discriminate between the two populations, since dead K562 cells display similar FLS characteristics as effector cells. Killed cells are stained with propidium iodide and followed by flow analysis. It was advisable to add the dye in the medium so that, as long as the target cells are killed they will also be stained. Moreover the flow cytometric and trypan blue evaluation of target cell death rate showed a stronger correlation than did either test with the conventional 51Cr release assay, the first two methods both being based on the same biological mechanism. PMID- 3343520 TI - An automated device for immunocytochemistry. AB - A microprocessor controlled device for automation of immunoenzyme histological and cytological staining procedures is described. As the sequence of processing is controlled by a computer program, the apparatus is flexible and the possibility of technical errors is reduced. PMID- 3343521 TI - Influence of granulocytes on brain edema, intracranial pressure, and cerebrospinal fluid concentrations of lactate and protein in experimental meningitis. AB - Brain water content (brain edema), intracranial pressure, and cerebrospinal fluid (CSF) concentrations of lactate and protein increased significantly during 24 h of experimental meningitis due to Streptococcus pneumoniae, but changes were similar in normal and neutropenic rabbits. In sterile meningitis induced by N formyl-methionyl-leucyl-phenyl-alanine (fMLP), low and high doses of fMLP were equally effective in inducing CSF pleocytosis, whereas only high doses of fMLP caused brain edema. High doses of fMLP injected intracisternally during pneumococcal meningitis also increased brain water content. The fMLP did not significantly increase intracranial pressure or CSF concentrations of lactate or protein in sterile or pneumococcal meningitis, nor did it cause brain edema in neutropenic animals. Thus, granulocytes may contribute to brain edema during meningitis if adequately stimulated, but intracranial pressure and CSF protein and lactate concentrations appear independent of granulocytes. Stimulation does not appear to occur early in meningitis, when granulocytes were without effect on brain edema. PMID- 3343523 TI - Comparison of molecular methods for subtyping patients and epidemiologically linked environmental isolates of Legionella pneumophila. AB - We used the molecular techniques of monoclonal antibody typing, plasmid analysis, and outer membrane protein profiling to subtype 159 patients' and environmental (water distribution system) isolates of Legionella pneumophila serogroup 1 from 18 institutions. The ability of these techniques to match patients' and epidemiologically linked environmental isolates from outbreaks of Legionnaires' disease at seven institutions was also compared. Two different panels of monoclonal antibodies (I and II) identified nine subtypes (one new disease causing subtype) and six subtypes, respectively. The Bellingham 1 subtype type was the most common among environmental isolates, and the Philadelphia 1 subtype predominated among patients' isolates from all institutions except the Veterans Administration Medical Center in Pittsburgh, Pennsylvania. The source of an isolate (patient vs. environment) and its monoclonal antibody subtype were significantly associated (P less than .01). With use of the molecular techniques tested, the subtypes of patients' isolates were identical to those of epidemiologically linked environmental isolates from the same hospital. PMID- 3343522 TI - Experimental Campylobacter jejuni infection in humans. AB - Two strains of Campylobacter jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 10(2) to 2 x 10(9) organisms, caused diarrheal illnesses. Rates of infection increased with dose, but development of illness did not show a clear dose relation. Resulting illnesses with strain A3249 ranged from a few loose stools to dysentery, with an average of five diarrheal stools and a volume of 509 mL. Infection with strain 81-176 was more likely to cause illness, and these illnesses were more severe, with an average of 15 stools and 1484 mL of total stool volume. All patients had fecal leukocytes. The dysenteric nature of the illness indicates that the pathogenesis of C. jejuni infection includes tissue inflammation. Ill volunteers developed a serum antibody response to the C. jejuni group antigen and were protected from subsequent illness but not infection with the same strain. PMID- 3343524 TI - Monoclonal antibody reactivity as a virulence marker for Legionella pneumophila serogroup 1 strains. AB - Using a panel of nine monoclonal antibodies, we subgrouped 85 environmental and 129 clinical Legionella pneumophila serogroup 1 isolates from Paris, France. Patients were unlikely to be epidemiologically linked either with each other or with the 44 sampled environmental sites (14 air conditioning systems and 30 buildings) that were selected at random in the Paris area. According to their monoclonal antibody patterns, isolates belonged to 14 subgroups. Monoclonal antibody 2 recognized 121 (93.8%) of 129 clinical isolates and 30 (35.3%) of 85 environmental isolates (P less than 10(-9)). Of the eight patients infected with L. pneumophila not recognized with monoclonal antibody 2, seven were immunocompromised; only 46.3% of the 121 patients infected with L. pneumophila reactive with monoclonal antibody 2 were immunocompromised (P = .02). We conclude that monoclonal antibody 2 can be used as a marker for the more virulent strains of L. pneumophila serogroup 1. PMID- 3343525 TI - Seroepidemiology of Cryptosporidium infection in two Latin American populations. AB - An enzyme-linked immunosorbent assay was used to examine randomly selected sera from 389 children and adults in Lima, Peru, and 84 children in Maracaibo and Caracas, Venezuela, for IgM or IgG antibody to Cryptosporidium. In Peru and Venezuela, 19.8% and 15.5% of the study populations, respectively, were positive for both specific IgG and IgM antibodies, a result consistent with active or recent infection and representing a larger percentage than normally reported from stool examinations of individuals seeking medical attention. Sixty-four percent of subjects from each country had detectable levels of specific IgG, indicating infection sometime in life. Detection of specific IgG increased in the two- to three-year-old age-group, a result suggesting that this is a common age for infection. Persistence of IgG and, less often, IgM antibody response over 12 mo occurred in some subjects, although the significance of this finding is uncertain. Our findings suggest that Cryptosporidium infections are endemic in the communities surveyed and that most residents have been infected. PMID- 3343526 TI - Serial quantitation of endotoxemia and bacteremia during therapy for gram negative bacterial sepsis. PMID- 3343528 TI - Pyrimethamine concentrations in serum and cerebrospinal fluid during treatment of acute Toxoplasma encephalitis in patients with AIDS. PMID- 3343527 TI - Diagnosis and evaluation of treatment of chronic strongyloidiasis in ex-prisoners of war. PMID- 3343529 TI - Disseminated herpes simplex type 2 and systemic Candida infection in a patient with previous asymptomatic human immunodeficiency virus infection. PMID- 3343530 TI - Actinobacillus actinomycetemcomitans and endocarditis. PMID- 3343531 TI - A dilute solution of vancomycin and heparin retains antibacterial and anticoagulant activities. PMID- 3343532 TI - IgM, IgG, and IgA antibodies in Yersinia infection. PMID- 3343533 TI - Lassa fever virus in Senegal. PMID- 3343534 TI - Gummatous syphilis: a reminder. PMID- 3343535 TI - Risk of pertussis-infected adults infecting newborn children. PMID- 3343536 TI - Phenotypes for group-specific component among patients exposed to human immunodeficiency virus by transfusions. PMID- 3343537 TI - Revaccination of previously vaccinated siblings of children with measles during an outbreak. PMID- 3343538 TI - Group G streptococcal bacteremia and parenteral drug abusers. PMID- 3343539 TI - Copper toxicity in Wilson's disease: an absorbing problem. PMID- 3343540 TI - Neutrophil adherence in diabetes mellitus. PMID- 3343541 TI - Endothelial-leukocyte adhesiveness. PMID- 3343542 TI - Neutrophil adhesive dysfunction in diabetes mellitus; the role of cellular and plasma factors. AB - We examined neutrophil adherence to bovine aortic endothelial cells in 26 patients with diabetes compared with age- and sex-matched controls. The adherence of chromium 51-labeled neutrophils from patients with diabetes in the basal state and after incubation with phorbol myristate acetate (PMA) but not N-formyl methionyl-leucyl-phenylalanine (FMLP) was decreased significantly. A subset of 16 of 26 patients demonstrated highly significant decreases in basal adhesion. No significant correlation was found between defective adherence and metabolic control as assessed by plasma glucose level (range 44 to 508 mg/dl) and hemoglobin A1 level (range 7.7% to 17.1%) at the time of study. Plasma from patients with diabetes increased adherence of both diabetic and control neutrophils in the basal state. The adherence-augmenting factor in diabetic plasma was found to be nonfilterable and partially heat labile and to manifest the characteristics of a protein. The adhesive effects of diabetic plasma were mediated through alterations in endothelium rather than neutrophils. Diabetic neutrophil aggregation induced by PMA, FMLP, and calcium ionophore was normal in all patients examined, regardless of the aggregating agent used. Fibronectin release in the basal state and after stimulation with FMLP was found to be comparable in diabetic and control neutrophils. These studies demonstrated intrinsic adhesive dysfunction of diabetic neutrophils and a factor or factors in diabetic plasma that enhanced adherence to endothelium. These cellular and humoral factors may act together to prevent tissue emigration of neutrophils and may contribute to the pathogenesis and susceptibility of infection in diabetes. PMID- 3343544 TI - Enhanced cytotoxic potential of alveolar macrophages from cigarette smokers. AB - Cigarette smoking increases the numbers and oxidative metabolism of alveolar macrophages. Increased production of superoxide (O2-) and H2O2 by alveolar macrophages may contribute to the pathogenesis of cigarette-induced lung diseases. The cytotoxicity mediated by alveolar macrophages from smokers (n = 11) and nonsmokers (n = 13) was compared in an in vitro assay in which the target cells were chromium 51-labeled lung explants. The spontaneous cellular cytotoxicity mediated by smoker macrophages was significantly greater than that of nonsmoker macrophages (cytotoxic index 20.3% +/- 1.9% compared with 5.5% +/- 0.9%, P less than 0.001). Phorbol myristate acetate significantly increased the cytotoxic index of nonsmoker macrophages but did not cause further increases in smoker macrophage killing. The antioxidants superoxide dismutase and catalase produced partial inhibition of smoker macrophage cytotoxicity, suggesting that target cell killing was mediated in part by oxidant mechanisms. Supplementation of smokers' diets with high-dose oral vitamin E failed to decrease smoker alveolar macrophage cytotoxicity. These findings demonstrate that smoker alveolar macrophages possess enhanced cytotoxic potential for normal lung parenchymal cells. PMID- 3343543 TI - Neutrophil adherence to human endothelial cells. AB - These studies evaluated whether the increased adherence of neutrophils to endothelium after exposure to lipopolysaccharide (LPS) endotoxin is primarily an effect on neutrophils or on endothelial cells. The studies demonstrate that preincubation of monolayers of human umbilical vein endothelial cells with LPS has a significantly greater effect on neutrophil adherence to endothelium than does preincubation of neutrophils with LPS (P less than 0.001 for each amount of LPS). Although the effect was small compared with incubation of endothelial cells with LPS, incubation of neutrophils with LPS did significantly increase their subsequent adherence to endothelial cells compared with controls (P less than 0.05). LPS was not toxic to either endothelial cells or neutrophils, as measured by the release of lactate dehydrogenase. Preincubation of endothelial cells with LPS at a concentration of 1.0 to 10 micrograms/ml maximally increased their ability to bind to neutrophils, and this effect was maximally expressed after 4 hours of exposure to LPS. In the assay, neutrophil binding to LPS-stimulated endothelial cells was rapid and did not increase after 30 minutes of coculture of neutrophils and endothelium. Morphologic studies demonstrated that LPS opened cell-to-cell junctions between endothelial cells. Neutrophils that attached to these monolayers of LPS-stimulated endothelial cells bound, primarily, to the margins of the endothelial cells and not to the underlying tissue culture dishes, which were exposed after incubation with LPS. These observations suggest that LPS increases neutrophil adherence primarily, but not solely, via an effect on endothelial cells. PMID- 3343545 TI - Protein phosphorylation during tannin-mediated activation of human platelets. AB - Experiments to explore human platelet protein phosphorylation changes and 5 hydroxytryptamine (5-HT) secretion after challenge with cotton bract tannin were performed. Quantitative changes in sodium phosphate phosphorus 32 incorporation in two platelet proteins of 19 kilodaltons (kd) and 47 kd were assessed by measuring protein band densities on autoradiographs of dried polyacrylamide gels. Secretion of 5-HT was assessed by 14C-5-HT release. Results show that tannin causes increases in phosphorylation of discrete platelet proteins that begin in less than 2 seconds. These increases are maximal in 1 minute for the 47 kd protein and in 3 minutes for the 19 kd protein. Fifty percent of maximum response required less than 2 seconds for both of these proteins, and 50% of maximum 5-HT secretion required 48 seconds. Dose-response studies comparing 0 to 50 micrograms/ml tannin with 0 to 1 U/ml human alpha-thrombin showed that tannin caused 5-HT secretion and protein phosphorylation changes that were very similar to those induced by human alpha-thrombin. Fifty micrograms per milliliter of tannin caused increases in 19 kd protein phosphorylation and 47 kd protein phosphorylation to 312% +/- 34% (SEM) and 204% +/- 13% of control, respectively (n = 14). One unit per milliliter of thrombin induced changes of 350% +/- 40% and 221% +/- 17% of control in the 19 kd and 47 kd proteins, respectively. Release of 5-HT by tannin and thrombin was 61% +/- 3% and 69% +/- 3% of total cellular 5-HT, respectively. Indomethacin had little inhibitory effect on activation by these two different agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343546 TI - Evidence of increased association of fibrinogen with platelets caused by sodium citrate. AB - Washed platelet suspensions are almost always prepared from blood anticoagulated with sodium citrate. Because citrate has been reported to affect platelet function, we examined the involvement of citrate on the platelet-fibrinogen interactions. More iodine 125-labeled fibrinogen was bound on washed platelets from citrate-anticoagulated blood (CP) than on washed platelets from non anticoagulated blood (PNB) obtained by the rapid gel filtration of native blood from the same donor. Scatchard analyses of the equilibrium binding data gave linear plots for PNB indicating a single class of binding sites with 16,480 +/- 2,800 fibrinogen molecules bound per platelet (Kd 5.6 x 10(-7) mol/L); CP gave curvilinear plots that, when resolved into two components assuming two classes of binding sites, gave a high-affinity site (4,950 +/- 970 molecules per platelet; Kd 1.29 x 10(-7) mol/L) and a low-affinity site (25,660 +/- 4,600 molecules per platelet; Kd 1.02 x 10(-6) mol/L). When blood from one donor was collected into 10 mmol/L and 20 mmol/L citrate, increased binding of 125I-fibrinogen was observed on platelets exposed to 20 mmol/L citrate. Exposure of PNB to varying citrate concentrations showed enhanced fibrinogen binding with increasing citrate concentrations; differences in the Kd values between non-citrate-treated PNB and citrate-treated PNB were apparent at about 7.5 mmol/L of citrate. The effects of citrate in increasing the association of fibrinogen with platelets were not caused by variations in the pH; although fibrinogen binding was diminished at low pH of the citrate used, more binding was observed in the presence of citrate than with buffer of the same pH. The effects of citrate appear to be on the platelet fibrinogen receptor because nonspecific binding was not affected by the citrate. Inasmuch as no carbon 14-labeled citric acid binding to platelets was observed, citrate may affect the platelet-fibrinogen interactions without binding to the platelets. We conclude that platelet exposure to citrate increases the fibrinogen binding and may lead to the appearance of curved Scatchard plots. PMID- 3343547 TI - Abnormal orthostatic changes in blood pressure and heart rate in subjects with intact sympathetic nervous function: evidence for excessive venous pooling. AB - The normal ranges of orthostatic changes in blood pressure and heart rate have been defined in 92 individuals aged 18 to 64 years. In 34 individuals whose symptoms (especially orthostatic light-headedness) suggested cerebral ischemia, but in whom none of the known causes of orthostatic hypotension could be identified, we have found one or more of five theoretically possible orthostatic circulatory derangements: systolic hypotension, diastolic hypotension, diastolic hypertension, excessive narrowing of the pulse pressure, and tachycardia after standing for at least 3 minutes. The orthostatic disorders of blood pressure and heart rate identified in the 34 patients were significantly reduced, almost always into the normal range, by external pressure of 45 to 50 mm Hg applied through an inflatable pressure suit. After labeling with sodium pertechnetate Tc 99m and reinjecting the erythrocytes contained in 3 to 6 ml blood, external gamma counting over a fixed site in the calf, both in the recumbent and in the standing posture, showed excessive gravitational pooling of blood in the legs of five patients with orthostatic diastolic hypertension, of four with orthostatic narrowing of the pulse pressure, and of 10 with orthostatic tachycardia alone. Plasma norepinephrine concentrations were usually normal in recumbency and elevated above normal limits during standing for 15 to 30 minutes in the 18 patients so observed. Red cell mass, plasma volume, and circulating blood volume were subnormal in more than half the seven patients in whom these measurements were made. We conclude that most of the patients with idiopathic sympathicotonic abnormalities of orthostatic blood pressure control have a venous pooling syndrome often aggravated by hypovolemia, the cause(s) of which remains to be determined. PMID- 3343550 TI - Health Fraud Hotline 1-800-432-9257. PMID- 3343548 TI - Mast cell granule enhancement of neutrophil chemiluminescence responses. AB - Cutaneous mast cell degranulation in rats results in tissue inflammation, and this species has therefore provided a useful model to study the pathogenesis of late phase reactions (LPRs). The mast cell dependency of LPRs has been confirmed by the demonstration that isolated rat mast cell granules (MCGs), when injected intradermally into rat skin, induce patterns of tissue inflammation similar to those seen after skin testing with anti-IgE antibody. Rat LPRs are neutrophil dependent, and, further, MCG-derived inflammatory factors can chemically attract rat neutrophils in vitro. To further study the relationships among MCGs, tissue inflammation, and neutrophil function, luminol-dependent chemiluminescence (CL) responses of rat peritoneal-elicited neutrophils in response to opsonized zymosan and phorbol myristate acetate (PMA) in the presence and absence of MCGs were analyzed. When MCGs (1.0, 10, and 100 micrograms/ml) alone were added to neutrophil suspensions, a rapid concentration-dependent increase in baseline CL responses was observed; these increases (maximum of sixfold) were modest, varied with cell concentrations, and followed different time courses compared with those seen after addition of preopsonized zymosan (0.5 mg/ml) (50-fold increases that peaked in 4 to 8 minutes). However, if neutrophils were preincubated (15 minutes) in the presence of MCGs, the CL response to opsonized zymosan (1.25 mg/ml) was significantly and synergistically enhanced compared with the response seen with MCGs alone. Similar but less pronounced effects were also noted after cell activation with PMA (2.5 and 25 ng/ml). To determine which component of the MCG was responsible for this enhancing activity, additional experiments were performed. Enhancement was still observed, albeit less intense, if MCGs were prepared membrane free and washed free of readily dissociable mediators such as histamine. Histamine (10(-6) and 10(-5) mol/L) had no enhancing effect nor did preparations of MCG membranes. MCG solubilization (3 mol/L NH4HCO3) revealed that the enhancing activity resided completely in the high molecular weight (greater than 10,000 daltons) fraction. Heat treatment of the granules and sodium azide preincubation completely abolished the enhancing effect. Exogenous horseradish peroxidase, at peroxidase activity levels contained within the MCGs (1 x 10(-4) to 10(-2) U/ml), reproduced the enhancing effect. After opsonized zymosan activation, neutrophils generated less H2O2 and superoxide anion in the presence of MCGs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3343549 TI - O.K. you big lug, now who's going to pay for all this mess? PMID- 3343551 TI - Scanning pacemaker for ventricular tachycardia. PMID- 3343552 TI - Angiolymphoid hyperplasia of the head and neck. AB - Angiolymphoid hyperplasia is a rare benign condition affecting the skin and subcutaneous tissue of the head and neck. Superficial (intradermal) lesions frequently affect the external ear and such a case presenting to an otolaryngologist is described. Clinically the disease is characterized by single or multiple plum-coloured nodules or plaques which are often itchy and may bleed with mild trauma. Histologically the lesions are composed of proliferating capillary vessels associated with a heavy inflammatory infiltrate including eosinophils and mast cells. The cause remains obscure. The lesions often persist for many years and may regress spontaneously. Several forms of treatment have been used, including cryosurgery, curettage and diathermy, radiotherapy and intralesional steroid injections. In this case the Argon laser was employed. PMID- 3343553 TI - Unusual presentations of extramedullary plasmacytoma in the head and neck. PMID- 3343554 TI - Cervico mediastinal emphysema due to oral blast. PMID- 3343555 TI - Scar formation following impulse noise-induced mechanical damage to the organ of Corti. AB - The terminal stages of the healing process of the organ of Corti in the chinchilla following exposure to blast-waves at 160 dB peak SPL, were studied by scanning electron microscopy (SEM) and by surface preparation technique. Extensive lesions of the sensory epithelia consisting in the absence of the OHC's, Deiter cells and Hensen cells, were replaced by scar tissue formed by single, flat, irregularly polygonal cells, arising from the Claudius cell area sealing off the endolymphatic spaces. When the pillar cells have been destroyed the scar epithelium from the Claudius cells has reached the IHC's, which show a remarkable resistance to acoustic trauma. Their presence in a large healed area may be the only remnants of a previous sensory region. When even the IHC's are absent, the entire organ of Corti can be replaced both by Claudius cells and by inner sulcus cells covering the denuded basilar membrane without any clear morphological difference between the two cellular sources. PMID- 3343556 TI - Revision stapes surgery. AB - The records of 120 patients who had undergone revision stapedectomy were analyzed to determine: (i) the causes of failure; (ii) how to prevent failure by taking precautions during primary surgery; (iii) hearing results; and (iv) possible identifying factors which might pinpoint those patients with a high risk of sensorineural deafness. A review of these cases demonstrates that the results of revision stapedectomy are different from those of primary stapedectomy. The commonest cause of failure was prosthetic dislocation (30.8 per cent), followed by fibrous adhesions (18.3 per cent) and otosclerotic regrowth (14.1 per cent). First revision operations resulted in post-operative bone-air gaps of 15 dB. or less in 46.5 per cent of cases, much better than 25 per cent for second revisions. Primary stapedectomy resulted in successful closure of the air-bone gap to 15 dB. or less in 89.5 per cent of cases. The sensorineural loss occurred in 11.3 per cent or first revisions and in 16.6 per cent of second revisions, as compared to 1.3 per cent after primary surgery. 'Dead ears' were encountered in 2.2 per cent of first revisions, as compared to nil in the primary group. PMID- 3343557 TI - Fluctuating hearing loss in presbyacusis. AB - Thirty-six patients with bilateral symmetrical presbyacusis who reported a temporary improvement in the hearing of one ear following a Valsalva's manoeuvre were further investigated. Bone conduction and air conduction thresholds, middle ear pressure and middle ear compliance were measured before and after Valsalva's manoeuvre in the ears which had a subjective improvement in hearing following auto-inflation. Bone conduction thresholds remained unaltered in 66 per cent of ears while average air conduction thresholds varied by less than 5 decibels. Middle ear pressure was unchanged in over half the ears tested and in 81 per cent of the ears there was no change in middle ear compliance. There appears to be no simple explanation for the temporary subjective fluctuation in hearing reported by patients with presbyacusis. PMID- 3343558 TI - The use of Walkman Mini-stereo system as a tinnitus masker. AB - A study was done on 41 patients to compare the use of the Walkman Mini-stereo system with different types of phones to mask tinnitus, by using music, or relaxation or different bands of noise similar to those generated by a tinnitus masker or pure tone, and it was found that the Walkman Mini-stereo system with any types of phone, was as effective, and more economic, both to patients and to the N.H.S., than traditional tinnitus maskers. It should be recommended for the management of tinnitus in preference to the traditional tinnitus maskers. PMID- 3343559 TI - Meningitis after trans-sphenoidal excision of pituitary tumours. AB - Between 1974 and 1986, eleven of 114 patients undergoing trans-sphenoidal removal of pituitary tumours developed meningitis despite prophylaxis, usually with chloramphenicol. Nine patients had cerebrospinal fluid rhinorrhoea and one died. A variety of pathogens was isolated, including enterobacteria, and four of the eleven were resistant to the antibiotics given as prophylaxis. Enterobacterial meningitis was always associated with infection of the sphenoidal sinus involving the muscle graft or nasal pack (five cases), and removal of the muscle graft was necessary in three cases despite the use of appropriate antibiotics. PMID- 3343561 TI - Reconstruction of the pharynx after laryngectomy and partial pharyngectomy. AB - Stricture formation may occur after pharyngolaryngectomy if less than one half of the circumference of the pharynx is available for primary closure. However, the alternative of total pharyngectomy with skin flap or visceral replacement carries with it a high mortality and morbidity rate. In an attempt to overcome these problems, a policy of patch grafting the pharyngeal defect with a myocutaneous flap or segment of free vascularised jejunum has been adopted whenever a strip of pharyngeal mucosa greater than one centimetre in width remains after excision of the tumour. A good post-operative swallow has been achieved in all cases. PMID- 3343560 TI - Laryngoplasty: results and problems after the creation of a neoglottis. AB - Voice rehabilitation in the laryngectomy patient has been a major goal of reconstructive laryngeal surgery. 36 patients underwent laryngectomy with the creation of a phonatory neoglottis as outlined by Staffieri. In 13 patients good voice rehabilitation was achieved. In 23 patients who failed to develop voice production, altered swallowing function was the major problem. PMID- 3343562 TI - Minitracheotomy and laryngeal function. A prospective study. AB - The 'minitracheotomy', i.e. an indwelling narrow-bore endotracheal tube which is inserted via the cricothyroid membrane to provide access for the removal of secretions from the tracheobronchial tree following major thoracic and abdominal surgery, has recently been developed. In order to investigate whether its use may be injurious to the larynx, a prospective study was carried out assessing laryngeal function pre- and post-operatively in 14 patients. No permanent changes in laryngeal function were found and it was concluded that, when used for short post-operative periods, the larynx is not adversely effected. PMID- 3343563 TI - Malignant external otitis: the use of oral ciprofloxacin. PMID- 3343564 TI - Chlorine and the eustachian tube. PMID- 3343565 TI - Sudden bilateral sensorineural hearing loss during treatment with dantrolene sodium (dantrium). PMID- 3343566 TI - Nasal regurgitation as the presenting symptom of rhinolithiasis. AB - Rhinoliths are not common but like other rare conditions have an attraction and therefore will be familiar. This case report has been presented as a reminder that perforation of the hard palate by a rhinolith does occur occasionally, and in this instance was a pleasant surprise to all concerned. PMID- 3343567 TI - Is vidian neurectomy worthwhile? AB - Vasomotor rhinitis is a frustrating experience both for the consultant and for the patient. The purpose of vidian neurectomy is to destroy the secretomotor nerve supply to the nasal mucosa, the main indication being severe intractable non-atopic vasomotor rhinitis. A review of 208 cases which have undergone transnasal vidian neurectomy by diathermy coagulation in the last five years is presented. The operation has proved worthwhile, the patients remaining symptom free in 92 per cent of cases (longest follow-up 5 years). There have been no complications. PMID- 3343568 TI - Tonsillar haemorrhage and measles. AB - A seven-year-old girl presented with life-threatening pharyngeal haemorrhage. This was subsequently found to arise from one tonsil, and a tonsillectomy eventually halted the bleeding. Two days later she developed measles, confirmed by serology and characteristic histology. Spontaneous tonsillar haemorrhage is extremely rare, and not previously reported in measles. PMID- 3343569 TI - Spontaneous perforation of the cervical oesophagus. PMID- 3343570 TI - Laryngo-tracheal stenosis in frontometaphyseal dysplasia. PMID- 3343571 TI - Verrucous carcinoma of the larynx: problems of diagnosis and treatment. AB - The first report of a case of verrucous carcinoma from Africa is presented. Problems of diagnosis and treatment are highlighted and the need for co-operation between the clinician and the pathologist for an accurate diagnosis is emphasized. PMID- 3343572 TI - Mucoepidermoid carcinoma of the trachea (a case report). AB - A case of mucoepidermoid carcinoma of the trachea in a 26-year-old female is presented. Diagnosis was confirmed by histopathology. On the basis of the clinical and histological picture, the tumour is classified as a low grade mucoepidermoid carcinoma. Conservative surgical treatment was the primary mode of treatment. The patient showed no clinical evidence of recurrence twelve months after local resection of the tumour. PMID- 3343573 TI - The treatment of facial haemangioma by percutaneous injections of sodium tetradecyl sulfate. AB - Sotradecol--sodium tetradecyl sulfate--is a sclerosing agent which has been used for years in the treatment of varicose veins, haemorrhoids and haemangiomata. Two cases of large haemangioma of the cheek are presented. Because surgical treatment posed many difficulties we decided to treat with sodium tetradecyl sulfate. Treatment was successful. PMID- 3343574 TI - Thyroid carcinoma, cataract and hearing loss in a patient after irradiation for facial hemangioma. AB - Thyroid carcinoma and cataract are well established complications of irradiation treatment to the head and neck region. Hearing loss is also a documented complication though less frequently reported. A rare case of a patient suffering from all three complications due to irradiation of the face by 24,000 rads for a hemangioma is reported. The pertinent literature is reviewed. PMID- 3343575 TI - Intratracheal thyroid. AB - A case of intratracheal ectopic thyroid tissue in the absence of clinical symptoms is described. It was an incidental finding observed at autopsy. PMID- 3343576 TI - Haemangiopericytoma of the submandibular gland (a case report). PMID- 3343577 TI - An interview with U.S. Senator Wyche Fowler. PMID- 3343578 TI - Points of view: physician dispensing of drugs. PMID- 3343579 TI - Rules of the Georgia State Board of Pharmacy. Chapter 480-28 practitioner dispensing of drugs. PMID- 3343580 TI - Medical Association of Georgia's 1987 report on human immunodeficiency virus. AIDS related complex and acquired immunodeficiency syndrome. PMID- 3343581 TI - Some comparisons between MAG and DHR's policy statements on AIDS. PMID- 3343582 TI - Georgia Department of Human Resources' five year plan on AIDS. PMID- 3343583 TI - The efficacy of measuring bone mineral density in asymptomatic women: a preliminary report. PMID- 3343584 TI - Syntactics of interpretation of negation: a developmental study. AB - Two cues are considered as syntactic indicators of the focus of a sentential negation in 7- and 10-year-olds and adults. One is the articles; it is proposed that an indefinite noun phrase is taken within the scope of a negative and a definite noun phrase outside it. A second cue is position. Based on R. S. Jackendoff's (1969, Foundations of Language, 5, 218-241) and P. A. Hornby's (1971, Child Development, 42, 1975-1988) work, subjects may be expected to take the second noun within the focus of sentential negatives regardless of the articles. In Experiments 1 and 2, subjects made picture selections for sentences of the form A/the Noun1 isn't V-ing the/a Noun2 and their passives. In Experiment 3, 10-year-olds describe the scenes of the sentences of the prior experiments. Noun position and article independently influenced the focus of the negation with age trends. Developmental differences in the uses of the articles are related to the acquisition of mastery of these linguistic markers. PMID- 3343585 TI - Children's perception of certain musical properties: scale and contour. AB - Children's perception of scale and contour in melodies was investigated in five studies. Experimental tasks included judging transposed renditions of melodies (Studies 1 and 3), discriminating between transposed renditions of a melody (Study 2), judging contour-preserving transformations of melodies (Study 4), and judging similarity to a familiar target melody of transformations preserving rhythm or rhythm and contour (Study 5). The first and second studies showed that young children detect key transposition changes even in familiar melodies and they perceive similarity over key transpositions even in unfamiliar melodies. Young children also are sensitive to melodic contour over transformations that preserve it (Study 5), yet they distinguish spontaneously between melodies with the same contour and different intervals (Study 4). The key distance effect reported in the literature did not occur in the tasks of this investigation (Studies 1 and 3), and it may be apparent only for melodies shorter or more impoverished than those used here. PMID- 3343587 TI - Bulimia in obese individuals. Relationship to normal-weight bulimia. AB - We compared 23 obese subjects meeting DSM-III criteria for bulimia with 47 obese nonbulimic subjects and 47 normal-weight bulimic subjects using structured diagnostic interviews. The obese bulimic subjects were similar to the normal weight bulimic subjects but different from the nonbulimic obese subjects in exhibiting a high lifetime rate of major affective disorder. However, the obese bulimic subjects were much less likely than the normal-weight bulimic subjects to use self-induced vomiting as a method of purging. These results suggest that obese individuals with bulimic symptoms may constitute a sizable but little recognized population. Further studies will be required, however, to assess whether the syndrome of bulimia in obesity represents a valid diagnostic entity. PMID- 3343586 TI - Spontaneous Ca2+ release from the sarcoplasmic reticulum limits Ca2+-dependent twitch potentiation in individual cardiac myocytes. A mechanism for maximum inotropy in the myocardium. AB - We hypothesized that the occurrence of spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), in diastole, might be a mechanism for the saturation of twitch potentiation common to a variety of inotropic perturbations that increase the total cell Ca. We used a videomicroscopic technique in single cardiac myocytes to quantify the amplitude of electrically stimulated twitches and to monitor the occurrence of the mechanical manifestation of spontaneous SR Ca2+ release, i.e., the spontaneous contractile wave. In rat myocytes exposed to increasing bathing [Ca2+] (Cao) from 0.25 to 10 mM, the Cao at which the peak twitch amplitude occurred in a given cell was not unique but varied with the rate of stimulation or the presence of drugs: in cells stimulated at 0.2 Hz in the absence of drugs, the maximum twitch amplitude occurred in 2 mM Cao; a brief exposure to 50 nM ryanodine before stimulation at 0.2 Hz shifted the Cao of the maximum twitch amplitude to 7 mM. In cells stimulated at 1 Hz in the absence of drugs, the maximum twitch amplitude occurred in 4 mM Cao; 1 microM isoproterenol shifted the Cao of the maximum twitch amplitude to 3 mM. Regardless of the drug or the stimulation frequency, the Cao at which the twitch amplitude saturated varied linearly with the Cao at which spontaneous Ca2+ release first occurred, and this relationship conformed to a line of identity (r = 0.90, p = less than 0.001, n = 25). The average peak twitch amplitude did not differ among these groups of cells. In other experiments, (a) the extent of rest potentiation of the twitch amplitude in rat myocytes was also limited by the occurrence of spontaneous Ca2+ release, and (b) in both rat and rabbit myocytes continuously stimulated in a given Cao, the twitch amplitude after the addition of ouabain saturated when spontaneous contractile waves first appeared between stimulated twitches. A mathematical model that incorporates this interaction between action potential-mediated SR Ca2+ release and the occurrence of spontaneous Ca2+ release in individual cells predicted the shape of the Cao-twitch relationship observed in other studies in intact muscle. Thus, the occurrence of spontaneous SR Ca2+ release is a plausible mechanism for the saturation of the inotropic response to Ca2+ in the intact myocardium. PMID- 3343588 TI - A twin study of the psychiatric side effects of oral contraceptives. AB - Oral contraceptive (ORC)-related depression and irritability are among the most commonly reported drug-induced psychiatric symptoms. To investigate the etiological role of genetic factors in ORC-related symptoms, we studied questionnaire responses in 715 monozygotic and 416 dizygotic volunteer twin pairs concordant for ORC usage. Biometrical genetic analysis indicated that the liability to ORC-related depression was clearly influenced by genetic but not familial-environmental factors. Similar, but less definitive, results were found for ORC-related irritability. Multivariate genetic analysis indicated that both the genetic and the individual-specific environmental factors that influenced the liability to ORC-related depression and irritability were largely distinct from those that influence baseline levels of psychiatric symptoms. Genes play an important etiological role in ORC-related psychiatric side effects. The genes that influence liability to these side effects appear to differ from those that are etiologically important in baseline psychiatric symptomatology. PMID- 3343589 TI - Temporal aspects of emergency room psychiatric evaluations. AB - The use of emergency room time by medical and psychiatric clinicians evaluating psychiatric patients was studied. The amount of time to the completion of the medical and the psychiatric evaluation and the actual amount of time of the psychiatric evaluation were compared over demographic, admission, diagnostic, and referral factors. Evaluations were completed closer to admission with patients admitted during the day and evening shifts and with patients having more obvious psychiatric problems, i.e., brought involuntarily, with a known psychiatric history, given a psychotic diagnosis in the emergency room, or subsequently sent to a psychiatric hospital. Such factors failed to affect the actual length of the psychiatric evaluation. The multiple time pressures in an emergency room setting appeared to affect when, but not how long, clinicians evaluated psychiatric patients. The time that emergency room clinicians take to begin evaluations of psychiatric patients may reflect important observational data that affect their temporal, diagnostic, and recommended treatment patterns. PMID- 3343590 TI - Patterns of familial alcoholism, alcoholism severity, and psychopathology. AB - The interrelationships among the severity of alcoholism, psychopathology/personality, and the degree of familial alcoholism were examined using the following four familial alcoholism classification schemes, which each differentiated three degrees of familial alcoholism: 1) conventional, compared alcoholics with no, nonparental, and parental alcoholic relatives; 2) lineality, distinguished between subgroups with alcoholism in neither, one, or both sides of their family; 3) generational, compared alcoholics having no, one, or two generations of familial alcoholism; 4) quantitative, credited one point for each first-degree and 1/2 point for each second-degree alcoholic relative. The subjects were 83 male alcoholic Veterans Administration inpatients 50 years of age or under. The Alcohol Use Inventory, various alcohol-related symptoms and behaviors, and laboratory values were used to evaluate the severity/pattern of alcoholism. Psychopathology/personality were measured by the MMPI, the Psychopathic State Inventory, the MacAndrew Alcoholism Scale, the Childhood Problem Behaviors Questionnaire, and the percentage of patients with an antisocial personality disorder (ASP) diagnosis. Surprisingly few subgroup differences were revealed in the severity/pattern of alcoholism. Only age at time of treatment and use of nonalcoholic drugs were associated with increasing familial alcoholism. On the other hand, childhood behavior problems, particularly antisocial behavior, and an ASP diagnosis were found to be associated with an increasing degree of familial alcoholism. The diagnosis of ASP was most apparent in the two-generational and bilineal alcoholics, while an increased degree of familial alcoholism was not associated with ASP for the conventional classification. Bilineal familial alcoholics also exhibited an MMPI profile reflective of a characterological disorder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343591 TI - Antecedents and consequences of cocaine abuse among opioid addicts. A 2.5-year follow-up. AB - During a 2.5-year follow-up of opioid addicts, we examined psychosocial antecedents and consequences of the onset and remission of cocaine abuse. Patients who never used cocaine were compared with those whose use increased or decreased along several dimensions of treatment outcome including drug abuse, legal, employment, family, social, psychological, and medical problems. Cocaine abuse had a marked impact on almost every outcome area except medical problems. Patients whose cocaine use increased during follow-up had more severe problems than either those whose use decreased or those who never used cocaine. Furthermore, the attainment of cocaine abstinence among abusers was associated with improved psychosocial functioning, whereas the onset of cocaine abuse was associated with increased problem severity. Compared with drug-free and detoxification alone treatments, methadone maintenance may minimize legal complications of cocaine abuse, but otherwise it did not significantly reduce psychosocial morbidity from increasing cocaine abuse. These findings suggest that treatment-seeking opioid addicts are vulnerable to wide-ranging deterioration when they become increasingly involved with cocaine but that with the attainment of abstinence many problem areas improve. PMID- 3343592 TI - Intimacy, power, and psychological well-being in medical students. AB - Numerous reports suggest that medical school has adverse psychological effects on medical students, although not all students are affected equally. The authors examined the effects of two social motives, the need for power and the need for intimacy, on measures of well-being and distress obtained throughout the undergraduate years. Medical students high in both power and intimacy motivation were more depressed, neurotic, fatalistic, and self-doubting than were their classmates. These effects began at the end of year 1, peaked in year 2, and disappeared by the end of clerkships. High intimacy-low power students had the highest levels of well-being. These effects were equally true in men and women and both support and render more precise prior role conflict explanations. PMID- 3343593 TI - Evaluation of the anticonvulsant and biochemical activity of CGS 8216 and CGS 9896 in animal models. AB - CGS 8216, a benzodiazepine-receptor ligand with inverse agonistic properties, and CGS 9896, which possesses partial agonistic or mixed agonist-antagonist properties were compared in a number of epilepsy models. The effect of CGS 9896 on the decrease in GABA levels induced by isoniazid was also investigated. CGS 9896 inhibited the kindling process in rats in that it delayed the development of overt seizures and the increase in the duration of afterdischarges. In a genetic rat model characterized by absence-like EEG patterns, CGS 9896 dose-dependently suppressed these spontaneously occurring discharges, while CGS 8216 had no effect. However, CGS 8216 antagonized the anticonvulsant action of CGS 9896. CGS 9896 protected mice against seizures induced by beta-vinyllactic acid, whereas CGS 8216 shortened the latency period before convulsions occurred. CGS 9896 retarded the onset of convulsive fits caused by isoniazid without preventing the decrease in GABA levels produced by that drug. These results confirm the anticonvulsant activity of CGS 9896 and demonstrate the inverse agonistic activity of CGS 8216. The profile of CGS 9896 in the above tests suggests that it might be an effective anticonvulsant, primarily in absence-type seizures. PMID- 3343594 TI - Chronic treatment with choline or scopolamine indicates the presence of muscarinic cholinergic receptor plasticity in the frontal cortex of young but not of aged mice. AB - Chronic treatment (2 weeks) with either scopolamine (4 mg/kg, once daily p.o.) or choline (200 mg/kg, once daily p.o.) resulted in a pronounced muscarinic cholinergic receptor up- or down-regulation in the frontal cortex of young (4 weeks) but not of aged (18 months) female mice. It is speculated that a similar age-related decline of muscarinic receptor plasticity might contribute to the profound dysfunction of cholinergic neurotransmission in Alzheimer's disease. PMID- 3343596 TI - Effect of adjuvant reserpine treatment on catecholamine metabolism in schizophrenic patients under long-term neuroleptic treatment. AB - The clinical and biochemical effects of adjuvant reserpine treatment were investigated in 12 chronic schizophrenic patients on long-term neuroleptic medication. The global severity of the symptoms using the Brief Psychiatric Rating Scale did not change significantly in the whole group, however, a moderate decrease in positive symptoms (factors though disturbance, activation and hostile suspiciousness) was observed for 5 patients. Cerebrospinal fluid (CSF) noradrenaline levels showed a consistent decrease, but other biochemical parameters (CSF dopamine metabolites, platelet MAO and serum dopamine-beta hydroxylase activities) did not change significantly. The changes of clinical symptoms and biochemical parameters did not show any correlation. PMID- 3343595 TI - Effects of fencamfamine on single unit activity of mesencephalic dopaminergic neurons in rats. AB - Systemic fencamfamine (0.5-16 mg/kg, i.v.) significantly but incompletely inhibited spontaneous activity of nigrostriatal and mesolimbic/mesocortical dopamine (DA) neurons. Inhibition was reversed by haloperidol (0.1 mg/kg, i.v.) and prevented by pretreatment with alpha-methyltyrosine (50 mg/kg, i.v.) plus reserpine (5 mg/kg, i.p.). Pretreatment with alpha-methyltyrosine alone attenuated inhibition at high but not low doses of fencamfamine. Microiontophoresed fencamfamine had little direct effect on DA neurons and did not consistently modulate the effects of co-microiontophoresed DA. In contrast, systemic fencamfamine blocked the inhibitory effects of low doses of apomorphine (10-40 micrograms/kg, i.v.). Fencamfamine appears to be an indirect DA agonist which interacts with both vesicular and newly synthesized DA storage pools. Fencamfamine may also cause a rapid desensitization to the effects of DA autoreceptor stimulation. PMID- 3343597 TI - Bovine and human pineal glands contain substantial quantities of endothelial cell stimulating angiogenic factor. AB - Using a quantitative assay the amount of a low Mr endothelial cell stimulating angiogenesis factor (ESAF) has been determined in human pineal glands and bovine brain, retina, pineal gland, liver and kidney. Pineal glands contain approximately ten times as much ESAF as the retina or grey and white matter from the cerebral cortex and a hundred times as much as highly vascular tissues such as liver and kidney. The relevance of these findings to the highly vascular nature of the pineal gland is discussed. PMID- 3343598 TI - The role of the posterior vermis of monkey cerebellum in smooth-pursuit eye movement control. I. Eye and head movement-related activity. AB - 1. The observation of smooth-pursuit eye and retinal image velocity signals in lobules VI and VII of the vermis has given rise to the hypothesis that a neural correlate of a target velocity signal exists in this region of the cerebellum (29). However, activity signaling head velocity is also required to regenerate a target velocity signal. Vermal Purkinje cell activity was, therefore, recorded during the performance of paradigms designed to dissociate head movement-related responses. 2. The activity of 107 Purkinje cells was found to be related to horizontal head velocity. Of these, 52% increased their discharge rate for ipsilaterally directed passive head movement (type I), and 48% were excited by contralateral head movements (type II). 3. In five Purkinje cells in which sufficient data were obtained, cell discharge rate increased monotonically with head velocity over the range of 5-40 deg/s. The sensitivity to head velocity at 0.4 Hz +/- 25 deg/s averaged approximately 0.5 spikes.s-1/deg.s-1 in a larger sample of cells (n = 39). The sensitivities to head velocity, at this same frequency and velocity, of type I and type II Purkinje cells were comparable at 0.44 and 0.51 spikes.s-1/deg.s-1, respectively. 4. The Purkinje cell responses led head velocity by an average of 12 degrees at 0.4 Hz +/- 25 deg/s of passive head rotation. The phase shifts associated with type I and II responses were similar with phase leads of 13 and 9 degrees with respect to head velocity, respectively. 5. A linear interaction of smooth-pursuit eye and head velocity signals was observed during the performance of a variety of antiphase and inphase eye and head movement paradigms. The results support the conclusion that some Purkinje cells in lobules VI and VII of the cerebellar vermis encode a gaze velocity signal. Contributions of the head velocity signal to the regeneration of target velocity are considered in a companion paper (32). PMID- 3343599 TI - The inhibition of cat lateral superior olive unit excitatory responses to binaural tone bursts. I. The transient chopper response. AB - 1. The temporal properties of lateral superior olivary (LSO) unit discharges to binaural tone bursts were studied to determine the general time course and statistical properties of these discharges and to provide a basis for extending a point process model of LSO unit monaural discharges to describe their binaural discharges. Single-unit activity was recorded extracellularly from the LSO of the anesthetized cat. The initial transient and the gross temporal features of LSO unit discharges to binaural simultaneous tone bursts are examined in this paper. 2. The poststimulus time (PST) histograms generated by LSO unit discharges to monaural and binaural tone bursts illustrated that the ipsilaterally elicited tone-burst discharges were most strongly inhibited during the initial segment of the binaural response and that the degree of inhibition decreased (i.e., discharge rate increased) as the poststimulus onset time increased. Hence, the contralateral inhibitory effect "adapts" in a manner similar to the ipsilaterally elicited discharges. 3. When the interaural level difference was decreased, the degree of discharge inhibition increased: the period of maximal inhibition spread to shorter and longer poststimulus onset times as the contralateral latency decreased and as the contralateral response magnitude increased. The latency of the inhibitory effect could decrease sufficiently to result in the suppression of the first spike of the ipsilateral discharge. Also, when the binaural stimulus was of sufficient intensity, an increase in spike output, the OFF discharge, was often observed during the last 1-10 ms of the response. 4. It was concluded that the initial and general time course of the binaural response could serve as cues of binaural stimulus level, interaural level differences, and interaural time-of arrival differences of high-frequency stimuli. The binaural response could be discriminated from a monaural response of similar discharge rate as the former either occurred with shorter latency or, when the first spike was suppressed, with much longer and/or more variable latency than the latter. The gross temporal differences between the monaural and binaural responses could be accounted for in terms of differences in certain gross temporal features (e.g., latency and adaptation) of the ipsilateral and contralateral responses. 5. The effect of stimulating the contralateral ear was not limited to the inhibition of discharges. The timing of a discharge to an ipsilateral stimulus could be perturbed (lengthened) by a contralateral stimulus at levels below that which suppressed the discharge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3343600 TI - The inhibition of cat lateral superior olive unit excitatory responses to binaural tone bursts. II. The sustained discharges. AB - 1. Preliminary to extending a point process model of lateral superior olive (LSO) unit activity to describe the units' binaural responses, the statistical properties of their discharges to binaural tone bursts were studied. The hypothesis that stimulation of the contralateral ear results in the simple reduction of the ipsilateral input was also examined. Single-unit activity was recorded extracellularly from the LSO of the anesthetized cat. The sustained discharges to characteristic frequency (CF) tone bursts presented simultaneously to the two ears were examined to determine whether the fine temporal (statistical) properties of these discharges differed from those of the discharges elicited by stimulating the ipsilateral ear alone. 2. The major effect of simultaneously stimulating the contralateral ear was the inhibition (i.e., the reduction in the mean discharge rate) of the sustained discharges to the ipsilateral control stimulus. The temporal pattern of discharges to the ipsilateral stimulus was also affected by stimulation of the contralateral ear. The discharges to binaural stimulation were more irregular in pattern: they often produced bimodal or multimodal interval histograms where unimodal interval histograms had been produced by the discharges to the ipsilateral control stimulus alone. The hazard function, an estimate of the unit recovery function, also often differed in form for the binaural and monaural discharges. 3. The binaural discharges could be distinguished from an ipsilaterally elicited discharge of comparable mean rate: there was a greater incidence of "short" interspike intervals in the binaural discharge. These short interspike intervals occurred most frequently in the discharges to the ipsilateral control stimulus alone and infrequently in the discharges to an ipsilateral stimulus that produced a mean rate similar to that of the binaural discharge. Thus the dead time estimates derived from the binaural discharges were more similar to the estimates derived from the ipsilateral control discharges than to those derived from the comparable-rate ipsilaterally elicited discharges. 4. Although the measures of the recovery properties of LSO unit discharges differed under monaural and binaural stimulus conditions, the serial dependence observed between successive interspike intervals in the binaurally elicited discharges was similar to that in the ipsilaterally elicited discharges. The conditional mean function, an estimate of the serial dependence or unit shifting function, did not differ greatly in form for the monaural and binaural discharges.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3343601 TI - The role of the posterior vermis of monkey cerebellum in smooth-pursuit eye movement control. II. Target velocity-related Purkinje cell activity. AB - 1. Purkinje cell activity was recorded from lobules VI and VII of the cerebellar vermis during the performance of visuooculomotor tasks designed to dissociate the signals related to head, smooth-pursuit eye, and retinal image movements. Task related modulations in the simple spike discharge rates of 157 cells were observed in three alert monkeys. 2. Of 65 Purkinje cells that were completely tested for all three signals, all exhibited smooth-pursuit eye movement-related activity. An additional vestibular or visual response was observed in 17 and 11% of the cells, respectively. Eye, head, and retinal image velocity signals were all recorded in the same unit in 52% of the Purkinje cells. The responses of 5% of the fully tested cells were associated with changes in the direction of eye, head, and retinal image movement. 3. The observed sensorioculomotor responses were direction selective in 98% of the Purkinje cells. For the Purkinje cells that were fully tested, 60% of the cells exhibited peak discharge rates for ipsilateral and 40% for contralateral eye velocity. Of these Purkinje cells, 45% exhibited eye, head, and retinal image velocity signals with equivalent direction preferences. 4. Of 42 Purkinje cells tested, 88% demonstrated some kinds of interactive responses during combined eye and sensory stimulation. The interaction of eye and head velocity signals has been discussed in a companion paper (38). The modulation in discharge rate observed during tracking in the presence of a random dot background pattern could be predicted from the dissociated responses to smooth pursuit in the dark and to movements of the background pattern during suppression of eye movements. 5. The sensitivity to smooth-pursuit eye velocity averaged 1.4 times the sensitivity to head velocity. In 80% of the Purkinje cells, however, the sensitivity to eye velocity exceeded the sensitivity to head velocity by an average of only 10%. The sensitivity to smooth-pursuit eye velocity averaged 1.6 times the sensitivity to retinal image velocity. 6. An increase in Purkinje cell discharge rate was observed during the open-loop period of the initiation of smooth-pursuit eye movements. This open loop response was consistent with the presence of a visual signal during ocular pursuit, since these cells were also shown to be responsive to a dissociated retinal image velocity signal. Furthermore, the magnitude of the open-loop response indicated an enhancement of the sensitivity to retinal image velocity when visual information became behaviorally significant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3343602 TI - Electrophysiological properties of neurons in the lateral habenula nucleus: an in vitro study. AB - 1. The electroresponsive characteristics of neurons in the lateral habenula were studied with intracellular recordings in a brain slice preparation of guinea pig diencephalon maintained in vitro. One hundred and two neurons met the criteria for recording stability, and of these, 18 were analyzed in detail. For these 18 neurons, the mean resting membrane potential was -61.9 mV, the mean input resistance was 124 M omega, and the mean spike amplitude of fast action potentials was 60.3 mV. 2. Lateral habenula neurons were found to have distinct patterns of activity dependent on membrane potential. At membrane potentials more positive than -65 mV, depolarization elicited trains of sodium-dependent fast action potentials. At membrane potentials more negative than -65 mV, slight depolarization elicited a tetrodotoxin-insensitive wave of depolarization, called a low-threshold spike (LTS), from which a burst of fast action potentials were triggered. The principal conductance underlying the LTS is a low-threshold calcium conductance, which is inactivated at membrane potential more positive than -65 mV and deinactivated when the membrane is hyperpolarized to potentials more negative than -65 V. 3. Upon termination of injected hyperpolarizing current, many neurons displayed oscillation in membrane potential at a frequency of 3-10 Hz, thereby generating repetitive bursts of fast spikes. 4. The pattern of neuronal activity in lateral habenula neurons was highly sensitive to slight alterations in membrane potential. The ability of these neurons to fire action potentials in two modes, tonically and in bursts, and the propensity of these neurons to dramatically alter their output in response to transient hyperpolarizing input, indicate that transmission through this relay in the dorsal diencephalic conduction system may be greatly augmented by relatively small hyperpolarizing influences on the individual neurons. PMID- 3343603 TI - Potassium-induced spontaneous electrographic seizures in the rat hippocampal slice. AB - 1. The CA1 region of rat hippocampal slices bathed in 8.5 mM interstitial K+ ([K+]o) exhibited spontaneous 20- to 90-s electrographic seizures at regular intervals of 1-8 min. In these same slices CA3 neurons generated spontaneous interictal bursts that propagated throughout the pyramidal cell subfields. CA1 electrographic seizures contained components reminiscent of discharges recorded in vivo during tonic-clonic motor seizures. The tonic phase lasted 1-10 s, consisted of a sustained depolarization and firing of CA1 pyramidal cells, and was associated with a negative extracellular potential in the cell layer. The clonic phase lasted tens of seconds and was composed of paroxysmal bursts with afterdischarges in pyramidal cells. 2. Electrographic seizures in CA1 were focal in nature in that they did not invade the CA3 region. Moreover, in approximately 85% of all slices the frequency and amplitude of interictal bursts in CA3 did not change during a CA1 seizure. 3. Both the tonic phase and each clonic discharge of an electrographic seizure were triggered synaptically by a CA3 interictal burst. Microlesions of the Schaffer collateral input abolished CA1 seizures in high [K+]o, and electrical stimulation of these afferents, in a pattern designed to mimic interictal input, restored seizures. Likewise, similarly patterned electrical stimulation of these fibers in slices bathed in high [K+]o with the CA3 region removed reliably evoked electrographic seizures with period and duration similar to spontaneous seizures in whole slices. 4. Electrographic seizures but not CA3 interictal bursts could be reversibly abolished by lowering the temperature from 35-37 to 28-30 degrees C or by the competitive N-methyl-D aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (5-10 microM). The inactive isomer, L-2-amino-5-phosphonovaleric acid (25 microM) did not eliminate seizures. 5. Neither the frequency nor intensity of interictal bursts recorded in the CA3 region changed in the minute preceding seizure initiation. Thus, although the presence of interictal input from the CA3 region is required for CA1 seizure generation, it appears that electrographic seizures do not result from a change in the quality or quantity of interictal input to the CA1 region. 6. During the 30- to 60-s period leading to a seizure the excitability of CA1 pyramidal cells appeared to increase gradually. Over the interseizure interval both CA1 pyramidal cells and glia gradually depolarized, the intensity of interictal bursts recorded in the CA1 region increased, and the extracellular DC potential recorded in the CA1 cell layer drifted negative.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3343604 TI - The spinal projection of individual identified A-delta- and C-fibers. AB - 1. Recordings were made from individual sensory neurons with an A-delta peripheral conduction velocity, either intrasomally in the L7 dorsal root ganglion, or extracellularly in Lissauer's Tract or in the dorsal root close to the root entry zone. The spinal projection of these afferents was assessed by their antidromic response to stimulation of the dorsal columns (DC) or Lissauer's Tract (LT) at the L5/L6 border. The adequate stimulus was also ascertained. 2. A delta-fibers could be divided into two groups: high-threshold mechanoreceptors from either skin or muscle (HTMRs) and low-threshold mechanoreceptors (LTMs), primarily Down Hairs. A third group of cells recorded intrasomally had broad spikes with shoulders on the downstroke characteristic of A-delta-nociceptors and were so classified provisionally, although no adequate stimulus could be identified. HTMRs and broad spike cells projected either in DC or LT, but LTMs projected only in DC, never in LT. About one-quarter of both groups failed to project rostrally as far as L5/L6. 3. Cells with unmyelinated axons recorded intrasomally were found to supply either low-threshold or high-threshold mechanoreceptors. Unlike A-delta-cells, all these cells had broad spikes with shoulders on the downstroke. Proportionally fewer C-fibers than A-delta-fibers projected as far as one segment rostral from their root entry zone. Of those that did, axons supplying low-threshold mechanoreceptors projected only in DC, whereas those innervating high-threshold mechanoreceptors could project either through LT or DC. 4. A-delta-fibers supplying LTMs and HTMRs exhibited a similar reduced conduction velocity was reduced even further in the spinal cord but much more for HTMRs than for LTMs. For C-fibers the conduction velocity decrease was more substantial in the dorsal root for HTMRs than for LTMs. 5. These findings suggest that axons innervating different peripheral receptors exhibit characteristic cellular properties. They confirm that the primary afferent component of Lissauer's Tract is specialized as a "pain pathway" but also indicate that the dorsal columns may play some role in the transmission of nociceptive information. PMID- 3343605 TI - Interval coding and band-pass filtering at oculomotor synapses in crayfish. AB - 1. Crayfish exhibit steady-state compensatory eyestalk rotations in response to rotations of the organism or the visual surround. For stimuli in the vertical planes (pitch or roll) the visual reflexes are mediated by identified visual interneurons [sustaining fibers (SFs)], which synapse on identified oculomotor neurons (Mns) (18). 2. The optimal visual stimulus is broad-field intense illumination (simulated skylight) distributed over the dorsal half of the cornea. These stimuli are also optimal for eliciting a regular pacing discharge in SFs with dorsal receptive fields (17). Since a unique discharge pattern is associated with the reflex stimulus, we proposed that the pacing discharge interval encodes the stimulus condition and is optimal for driving the motoneuron discharge. 3. The cross-correlation of SF and Mn impulse trains exhibit large peaks (or troughs) at short latencies associated with strong excitatory (or inhibitory) interactions and "secondary effects" at longer delays associated with the periodicity of the Mn impulse train. The secondary peaks and troughs indicate delayed periods of elevated or depressed Mn excitability synchronized to the reference train (SF) events. From the structure of the cross-correlograms and the motoneuron autocorrelograms we predicted that the spike-to-spike synaptic throughput should be differentially sensitive to the various classes of SF interspike intervals. 4. The hypotheses were tested with logical-correlation functions that directly measure the relative synaptic efficacy of several classes of SF intervals during a continuous train at constant mean rate. The results indicate that the SF-to-Mn excitatory synapse is maximally driven by SF impulses separated by approximately 85 ms. These events are about 2.5 times as effective as the impulses associated with short intervals (less than 20 ms) and 1.4 times as effective as the spikes of long intervals (250 ms). The optimal interval in the various preparations is highly to correlated to the period of the Mn discharge and the SF modal interspike interval. Inhibitory synapses are also differentially sensitive to the SF interspike intervals, but they exhibit summation rather than depression in response to short interspike intervals. 5. These results are generally consistent with previously formulated relationships (39), which govern the synaptic modulation of pacemakers and may apply to any synaptic interaction in which the postsynaptic neuron exhibits a regular discharge. 6. Combinations of long and short intervals with the same mean rate as the optimal interval are not as effective in driving the SF-to-Mn synapse.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3343606 TI - The natural history of unruptured intracranial arteriovenous malformations. AB - The authors conducted a long-term follow-up study of 168 patients to define the natural history of clinically unruptured intracranial arteriovenous malformations (AVM's). Charts of patients seen at the Mayo Clinic between 1974 and 1985 were reviewed. Follow-up information was obtained on 166 patients until death, surgery, or other intervention, or for at least 4 years after diagnosis (mean follow-up time 8.2 years). All available cerebral arteriograms and computerized tomography scans of the head were reviewed. Intracranial hemorrhage occurred in 31 patients (18%), due to AVM rupture in 29 and secondary to AVM or aneurysm rupture in two. The mean risk of hemorrhage was 2.2% per year, and the observed annual rates of hemorrhage increased over time. The risk of death from rupture was 29%, and 23% of survivors had significant long-term morbidity. The size of the AVM and the presence of treated or untreated hypertension were of no value in predicting rupture. PMID- 3343607 TI - A modified extended middle cranial fossa approach for acoustic nerve tumors. Results of 125 operations. AB - During the past 10 years, 125 operations for acoustic nerve tumors were performed on 114 patients at the authors' institution using a modified extended middle cranial fossa approach. This approach is based on a combination of King and Morrison's translabyrinthine-transtentorial approach and on the extended approach through the middle cranial fossa described by Bochenek and Kukwa. There were two hospital deaths (operative mortality 1.6%). In 102 operations on the initial tumor, total removal was performed in 89 cases (87%), and in 71 (80%) of these the facial nerve was anatomically preserved. Intracranial end-to-end anastomosis was performed on five of the 18 sacrificed facial nerves; a facial-hypoglossal anastomosis was carried out in the remaining 13 patients and in five (7%) of the 71 patients whose anatomically preserved facial nerve functioned poorly. In seven (39%) of the 18 patients in whom an attempt to preserve hearing was made, postoperative hearing was saved. In 23 operations on 17 patients for recurrent tumors, most of which had previously been removed subtotally via the suboccipital approach, total removal was accomplished in 13 (57% of the 23 reoperations and 76% of the 17 patients). At reoperation, the facial nerve was preserved in six (55%) of the 11 patients in whom the facial nerve had not been sacrificed. Postoperative leakage of cerebrospinal fluid occurred in 11 cases (8.8%), with rhinorrhea in 10 cases and otorrhea in one. Five of the fistulas were corrected by surgery and the rest healed spontaneously. Other complications were not significant. PMID- 3343608 TI - Updated assessment and current classification of spinal meningeal cysts. AB - The classification of spinal meningeal cysts (MC's) in the literature is indistinct, confusing, and in certain categories histologically misleading. Based on a series of 22 cases, the authors propose a classification comprising three categories: spinal extradural MC's without spinal nerve root fibers (Type I); spinal extradural MC's with spinal nerve root fibers (Type II); and spinal intradural MC's (Type III). Although water-soluble myelography may disclose a filling defect for all three categories, computerized tomographic myelography (CTM) is essential to reveal communication between the cyst and the subarachnoid space. Communication demonstrated by CTM allows accurate diagnosis of a spinal MC and rules out other mass lesions. Magnetic resonance imaging appears useful as an initial study to identify an intraspinal cystic mass. Final characterization is based on operative inspection and histological examination for all three categories. PMID- 3343609 TI - Benign intraparenchymal brain cysts without an epithelial lining. AB - Three patients are presented who had benign intraparenchymal cysts of the brain. The wall of each cyst was biopsied and had no epithelial lining or other microscopic feature to indicate the etiology of the cyst. The authors review published information about benign brain cysts and speculate about the origin of those having a wall composed solely of neuroglial tissue. PMID- 3343610 TI - Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine. AB - Forty-seven patients with medulloblastoma were treated postoperatively with procarbazine, followed by craniospinal radiation therapy in combination with hydroxyurea. The radiation dose to the posterior fossa was 55 Gy; the spinal cord received 25 Gy and the whole brain 25 to 35 Gy (mean 33 Gy). Seventeen tumors recurred. Only one initial recurrence was in the spinal subarachnoid space; 10 (59%) were in the posterior fossa, and four (24%) were supratentorial. The estimated 5-year disease-free survival probability was 55%; the 5-year overall survival rate was 66%. Myelotoxicity occurred in 38% of patients, but in only one case was it severe enough to warrant reducing the total dose of radiation. It was concluded that good-risk medulloblastoma patients may be treated with radiation dosages as low as 25 Gy to the spinal axis and to the whole brain without increasing the risk of recurrence outside the posterior fossa. Chemotherapy with procarbazine followed by radiation therapy and hydroxyurea during radiation therapy was well tolerated and may play a role in reducing radiation dosages outside the posterior fossa. PMID- 3343611 TI - Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage. AB - A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned. PMID- 3343612 TI - Symptomatic low intracranial pressure in shunted hydrocephalus. AB - Fourteen patients with ventricular cerebrospinal fluid shunts in place for chronic hydrocephalus presented with a history and neurological deficits usually associated with high intracranial pressure (ICP) caused by an obstructed shunt system. However, the symptoms were characteristically present when the patient was upright and active, and were usually relieved by lying down. The symptoms of intermittent headache, nausea, emesis, lethargy, and diplopia were associated with paresis of upward gaze or minimal strabismus. Measurement of ICP showed unexpected dramatically low levels with a marked drop in pressure when the patient was in the upright position, whereas ICP was near normal when the patient was supine. The low ICP was corrected by insertion of a high-pressure Flo-Control valve into the shunt system already in place. Postoperatively, the immediate clinical improvement and more normal ICP measurements were striking. The important clinical finding in this group of patients was the presence of disabling symptoms which occurred when the patients were up and active and which were relieved by lying down. Measurements of ICP with the patient in the supine and then in the upright position were critical in establishing an accurate diagnosis of symptomatic low ICP in these hydrocephalic patients with indwelling shunts. With the patient in the Trendelenburg position, ICP showed a marked increase, as expected; in some patients this position was prescribed as treatment for several days before surgery. PMID- 3343613 TI - Outcome from head injury related to patient's age. A longitudinal prospective study of adult and pediatric head injury. AB - A series of 8814 head-injured patients admitted to 41 hospitals in three separate metropolitan areas were prospectively studied. Of these, 1906 patients (21.6%) were 14 years of age or less. This "pediatric population" was compared to the remaining "adult population" for mechanism of injury, admission Glasgow Coma Scale score, motor score, blood pressure, pupillary reactivity, the presence of associated injuries, and the presence of subdural or epidural hematoma. The relationship of each of these factors was then correlated with post-traumatic mortality. Except for patients found to have subdural hematoma and those who were profoundly hypotensive, the pediatric patients exhibited a significantly lower mortality rate compared to the adults, thus confirming this generally held view. This study indicates that age itself, even within the pediatric age range, is a major independent factor affecting the mortality rate in head-injured patients. PMID- 3343614 TI - Posttraumatic cerebral hemispheric swelling. Analysis of 55 cases studied with computerized tomography. AB - The authors have analyzed the clinical course and intracranial pressure (ICP) changes in 55 severely head-injured patients presenting with bulk enlargement of one cerebral hemisphere within a few hours after trauma. These patients represent 10.5% of a series of 520 patients with severe head injury studied with computerized tomography (CT). Cerebral hemispheric swelling has the highest mortality rate and the shortest survival period after trauma in all series of severe head injury. In this series, it was associated with an ipsilateral subdural hematoma of variable size in 47 patients (85%) or with a large epidural hematoma in five patients (9%); in three patients (5.4%) it occurred as an isolated lesion. Evacuation of an associated extracerebral hematoma, which was performed within 4 hours after injury in only 20% of cases, scarcely changed the patients' preoperative neurological status. The high incidence of arterial hypotension and/or hypoxemia at admission (47% of cases) and the severity of the clinical presentation (82% of patients scored 5 points or less on the Glasgow Coma Scale, 74% had unilateral or bilateral mydriasis, and 80% had an initial ICP above normal) correlated with a very poor final outcome (87% mortality). Only one of the 11 patients with normal initial ICP continued to have normal pressure throughout the course. High-dose thiopental failed to control severe intracranial hypertension in 24 patients (51%) who had a fulminant, malignant course. A transient decrease in ICP elevation was achieved in 15 patients (31.4%) and definitive control in eight patients (17%), among whom were the seven survivors in this series. In the authors' experience, once ICP is controlled, barbiturate administration should not be discontinued until a control CT scan shows complete disappearance of the mass effect. PMID- 3343615 TI - Characterization of neuroectodermal antigen by a monoclonal antibody and its application in CSF diagnosis of human glioma. AB - Monoclonal antibodies were produced by immunization of the human glioma cell line SK-MG-4. One of the antibodies, designated G-22, reacted with 18 of 20 glioma cell lines, two melanoma cell lines, and three lung cancer cell lines, but not with 39 cell lines derived from sarcoma, carcinoma, or hematopoietic tumors. The antigen was expressed in the brain of human fetuses in early gestation (9 weeks) but not in late gestation (8 months) or in normal adult brain, suggesting that the antibody recognizes neural differentiation antigens expressed by neuroectodermal origin. A high incidence of positive antigens has been observed in gliomas but not in the other neural tumors, such as ependymomas, meningiomas, and neuroblastomas. Thus, the antigen defined by the G-22 monoclonal antibody could be defined as glioma-associated antigen. Pulse-labeling with tritiated leucine and subsequent immunoprecipitation of the solubilized cell membrane revealed that the antigen recognized by this antibody had a molecular weight of 67 kD on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It was shown by dot-blot enzyme-linked immunospecific assay (ELISA) that the antigen could be detected in the cerebrospinal fluid (CSF) from patients with gliomas. From analysis of affinity chromatography and SDS-PAGE, the antigen present in the CSF had a molecular weight similar to that of a 1% Nonidet P-40 (NP-40) extract from a glioma cell line. When the antigen in CSF was quantitatively assayed by ELISA, the mean antigen level (expressed as optical density at 450 nm) in the CSF of seven patients was 0.8 +/- 0.28 (mean +/- standard deviation), which was significantly higher than the 0.38 +/- 0.14 level observed in the CSF of 15 patients with nonglioma brain tumors and the 0.23 +/- 0.09 level in the CSF of four patients without brain tumors. These results indicate that the monoclonal antibody G-22 is useful for the diagnosis of glioma. PMID- 3343616 TI - Effects of the 21-aminosteroid U74006F on experimental head injury in mice. AB - The ability of a novel non-glucocorticoid 21-aminosteroid U74006F to inhibit lipid peroxidation of central nervous system tissue in vitro and to enhance the early neurological recovery and survival of mice after a severe concussive head injury is described. In the in vitro studies, U74006F was found to be an extremely potent inhibitor of lipid peroxidation in an assay system where the glucocorticoid steroid methylprednisolone and the non-glucocortoid steroids U72099E and U75718A were almost completely ineffective. In the head-injury studies, unanesthetized male CF-1 mice were subjected to a 900 gm-cm closed head injury produced by a 50-gm weight being dropped 18 cm. This concussive injury resulted in immediate unconsciousness (loss of righting reflex) in all animals and death in approximately 30%. Survivors received a tail vein injection of either vehicle or U74006F (0.001 to 30 mg/kg) within 5 minutes postinjury. Their neurological status was evaluated 1 hour later using a grip test. The grip-test score indicated that intravenous administration of a single dose of U74006F resulted in a significant improvement by as much as 168.6% in the neurological status 1 hour postinjury over a broad dose range (0.003 to 30 mg/kg). A 1-mg/kg dose given intravenously within 5 minutes and again at 1 1/2 hours after a severe injury, in addition to improving early recovery, also increased the 1-week survival rate to 78.6% compared to 27.3% in vehicle-treated mice (p less than 0.02). The compound was also effective in enhancing early recovery after a more moderate injury. This study demonstrates that early treatment after severe concussive head injury with a potent inhibitor of iron-dependent lipid peroxidation can significantly benefit the injured brain in mice and promote both early neurological recovery and long-term survival. PMID- 3343617 TI - Effects of the 21-aminosteroid U74006F on posttraumatic spinal cord ischemia in cats. AB - The ability of a single intravenous dose of the 21-aminosteroid U74006F to affect the development of posttraumatic spinal cord ischemia was examined in pentobarbital-anesthetized cats. After surgical preparation, each animal received a 300 gm-cm contusion injury to the exposed L-3 vertebral segment, followed by a single bolus injection of vehicle or U74006F (3 or 10 mg/kg) at 30 minutes postinjury. Spinal cord white matter blood flow (SCBF) was measured by hydrogen clearance in the dorsolateral funiculus in the center of the injured segment before and at various times up to 4 hours after injury. In vehicle-treated cats, there was a progressive decline in SCBF over the course of the experiment. By 4 hours postinjury, SCBF had decreased from a preinjury value of 15.9 +/- 2.4 ml/100 gm/min (mean +/- standard error of the mean) to 5.8 +/- 0.8 ml/100 gm/min, representing a decline of 63.5%. In contrast, the SCBF measured 4 hours postinjury in cats that were treated with a single 10-mg/kg dose of U74006F was 13.6 +/- 1.7 ml/100 gm/min (p less than 0.001 vs. vehicle). Animals that received a 3-mg/kg intravenous dose of U74006F displayed a drop in SCBF equal to that of vehicle-treated cats. However, when a 3-mg/kg dose of U74006F was given to four vehicle-treated cats at the end of the experiment, a partial reversal of ischemia was recorded. Blood flow increased within 30 minutes from a mean of 4.5 +/- 0.8 to 7.4 +/- 1.0 ml/100 gm/min or an increase of 64.4% (p less than 0.05). This rather surprising effect of U74006F in reversing posttraumatic ischemia once it has developed significantly is not shared by a 30-mg/kg intravenous dose of methylprednisolone sodium succinate (MP), although MP has previously been shown to attenuate the posttraumatic drop in SCBF when given before the SCBF drop occurs. The mechanism of action of U74006F in antagonizing posttraumatic ischemia development is believed to involve the ability of the compound to inhibit iron dependent lipid peroxidation in central nervous system tissue. PMID- 3343618 TI - Microcystic spinal cord degeneration causing posttraumatic myelopathy. Report of two cases. AB - Two cases of progressive myelopathy occurring years after incomplete cervical spinal cord injury are presented. In both patients, the clinical features, as well as the "bull's-eye" appearance of the delayed computerized tomography (CT) myelography study and the circumscribed low density of the magnetic resonance image, were consistent with posttraumatic syringomyelia, but surgical exploration including intra-operative spinal sonography failed to reveal a syrinx. Although arachnoiditis was present in both patients, the striking abnormality found at surgery was the softened appearance and the microcystic degeneration of the cord. The microcystic spinal cord degeneration found in these cases represents a previously undescribed cause of late deterioration after spinal cord injury that may mimic the clinical, CT-myelographic, and magnetic resonance features of posttraumatic syringomyelia. PMID- 3343619 TI - Intraventricular varix causing hemorrhage. Case report. AB - A case of a cerebrovascular varix located in the right lateral ventricle is reported. The patient suffered intraventricular and subarachnoid hemorrhages. The intraventricular varix was coagulated and excised. PMID- 3343620 TI - Subcutaneous sacrococcygeal ependymoma with inguinal lymph node metastasis. Case report. AB - A patient with a subcutaneous sacrococcygeal ependymoma and metastasis to the inguinal lymph nodes is presented and his treatment is described. Previous reports on sacrococcygeal ependymoma are reviewed. PMID- 3343621 TI - Treatment of resistant intracranial hypertension with hypertonic saline. Report of two cases. AB - The authors describe two patients with traumatic cerebral edema and intracranial hypertension in whom the continued use of mannitol and furosemide resulted in a progressive lessening of the effect of these agents on the intracranial pressure (ICP) and caused prerenal failure. Intravenous administration of hypertonic saline (50 ml and 20 ml of a 5-mmol/ml saline solution over 10 minutes in Cases 1 and 2, respectively) produced a prolonged reduction in the ICP and improved renal function in both cases. It is suggested that if a reduction in ICP without diuresis is required in patients with traumatic cerebral edema, treatment with intravenous hypertonic saline should be considered. PMID- 3343622 TI - Focal cortical dysplasia. Case report. AB - A histologically confirmed case of focal dysplasia of the cerebral cortex is presented. The computerized tomographic, electroencephalographic, pathological, and angiographic findings are discussed with respect to this rare developmental disorder. A review of the literature is presented with a possible etiology for this condition. PMID- 3343623 TI - Water-soluble contrast medium for intraoperative evaluation of anterior cervical discectomy. Technical note. AB - When anterior cervical discectomy is performed for either "hard" or "soft" cervical disc herniation using either the Cloward approach or simple discectomy, it is often difficult to confirm intraoperatively the adequacy of the lateral, superior, and inferior margins of the dissection. Placement of a nonionic contrast material, iohexol, into the disc space before obtaining anteroposterior and lateral x-ray spine films can indicate the adequacy of the margins of dissection of the soft disc or bone ridge to prevent a poor operative result. PMID- 3343624 TI - Arnold-Chiari malformation in children. PMID- 3343625 TI - Type III collagen deficiency and type IV Ehlers-Danlos syndrome. PMID- 3343626 TI - Results of chymopapain chemonucleolysis. PMID- 3343627 TI - Energy-speed relationship of walking: standard tables. AB - The energy expenditure of level walking was measured in 260 normal male and female subjects walking around a 60.5m-circular outdoor track. Subjects were divided into four age groups (children, 6-12 years; teens; young adults, 20-59 years; and senior adults, 60-80 years). Oxygen consumption was measured with a modified Douglas Bag technique during the fourth and fifth minutes of each trial. Standard tables according to age and sex were derived for the average energy expenditure (rate of oxygen uptake, energy cost per meter, and heart rate) and for the gait characteristics (speed, cadence, stride length) at the subjects' customary slow, normal, and fast walking speeds. Statistical analysis was performed to determine the energy-speed relationship for the different age groups to derive normative tables for the rate of oxygen uptake throughout the range of customary walking velocities. PMID- 3343628 TI - Effects of ankle taping on the motion and loading pattern of the foot for walking subjects. AB - Gait analysis was used to compare the ground reaction forces, ankle and foot rotations in the sagittal plane, and the center of pressure pattern beneath the right feet of seven normal subjects walking barefoot, with and without their right ankles taped in the neutral position. Instrumentation included a force plate, ankle goniometer, and two accelerometers mounted on top of the foot. The ground reaction forces showed no changes between the same ankle, taped and untaped. Taping served to reduce the range of ankle rotations in the sagittal plane by approximately 20%, with a subsequent increase in the rotation about the metatarsal heads during heel-up. Heel-up occurred earlier in stance when the ankle was taped than with no taping. The vertical force graph was integrated over time when the center of pressure was located beneath the heel and the ball, resulting in two impulse measurements. The heel impulse decreased for each of the 7 subjects and 6 of the 7 subjects displayed an increase in the ball impulse due to taping, indicating that taping served to shift the load-time history away from the heel and toward the ball. The results of this study may apply to fused ankle patients, who may suffer forefoot abnormalities subsequent to ankle fusion surgery. PMID- 3343629 TI - Intramuscular pressure in the supraspinatus muscle. AB - Shoulder pain correlated to manual labour is an increasing problem. The etiology is multifactorial and often unclear. High local muscle load and muscle ischemia in the supraspinatus muscle is present in elevated arm positions, as shown in several electromyographic studies. The purpose of this study was to evaluate intramuscular pressure (IMP) as a way to describe local muscle load in the supraspinatus muscle. Measurements were made in 15 arm positions, and with hand loads of 0, 1, or 2 kg weight, in 12 shoulders. The IMP was recorded with microcapillary infusion technique. The method was found to be suitable in recording IMP at rest and during exercise. High intramuscular pressures, i.e., above 50 mm Hg (6.7 kPa), were seen in moderate humeral abduction. The IMP increased further in abduction up to 90 degrees, where mean IMP was 122 mm Hg (16.2 kPa). Added hand load increased intramuscular pressure in all positions except in shoulder flexion of 135 degrees. The study thus demonstrated that intramuscular pressure offers important information about the load on the supraspinatus muscle in different positions of the arm. The results indicate that fatigue and shoulder pain related to elevated arm positions may be caused by muscle ischemia induced by the high intramuscular pressure present in these positions. PMID- 3343630 TI - Pulsing electromagnetic field stimulation of the in vitro growth plate. AB - Specific pulsing electromagnetic fields (PEMFs) have been used to stimulate growth and repair of osteogenic tissues; however, the basis for this specificity is unknown. Previously, we determined the relevant electromagnetic field parameters of the clinically used PEMF and independently verified the beneficial effects of PEMFs on the rabbit fibula fracture healing model. The goal of the present study was to develop an in vitro model that would permit the effectiveness of various electric and magnetic field components of the PEMF to be determined. The costochondral junction (CCJ) of the 21-day-old rat was exposed in vitro to PEMFs with various electric and magnetic field component amplitudes. Response of this model to PEMFs was determined by nondestructive macrophotographic measurement of CCJ growth. Preliminary data indicated that temperature effects were present in this in vitro system. Subsequent experiments designed to separate the effects of temperature and PEMFs on the growth of CCJs in tissue culture were performed. Results indicate that accurate and frequent temperature measurements must be made for in vitro models being used to study effects of PEMFs. Small temperature differences induced by the coils used to produce PEMFs in the CCJ experimental system can have significant stimulatory effects, and the combined effects of temperature and PEMFs are not linearly additive in this model. Furthermore, our results suggest that thermal and PEMF stimuli could affect macrophotographically measured growth of the CCJ by separate mechanisms or could have a synergistic effect. Therefore, PEMF stimulation experiments should be performed under strictly "athermal" conditions. PMID- 3343631 TI - Time-varying magnetic fields: effects of orientation on chondrocyte proliferation. AB - The purpose of this study was to determine the effect of orientation of pulsed electromagnetic fields (PEMFs) on cellular proliferation and extracellular matrix synthesis. Bovine articular chondrocytes were cultured in PEMFs (repetitive pulse at 72 Hz) generated using Helmholtz coils oriented either parallel (horizontal) or perpendicular (vertical) to the plane of cell adhesion. Dissipation of signal energy in the form of heat increased the temperature of the PEMF coils by 2 degrees C and the tissue culture medium by 1 degree C. Therefore, control coils, which emitted no PEMFs, were heated to the temperature of PEMF coils by circulating water. Chondrocytes were cultured in 16-mm-well culture plates, and the data for individual wells were pooled as triplicates. Although not observed by microscopic examination of individual wells, positionally dependent electric field effects may be minimized by this approach. PEMFs generated by coils oriented vertically significantly decreased chondrocyte proliferation. The effect was dependent on the concentration of serum in the culture media. At 3% serum concentration, the total cell number attained after 10 days of culture was reduced by 50% in stimulated cultures when compared with controls. At 5% serum concentration, there was no effect. PEMFs applied by coils oriented horizontally did not alter proliferation of articular chondrocytes. PEMFs had no effect on synthesis of extracellular matrix by chondrocytes plated at high density, irrespective of orientation. PMID- 3343632 TI - Hydraulic resistance: a measure of vascular outflow obstruction in osteonecrosis. AB - This study introduces hydraulic resistance (HR) as a new method to measure intraosseous vascular outflow resistance in the human proximal femur. HR is the standard measure of resistance to fluid flow in porous matrices and is derived from serial pressure/flow determinations. Eighteen hips were studied in 11 patients taken to surgery for core decompression therapy of presumable atraumatic osteonecrosis of the femoral head. HR was much higher in osteonecrotic (174 +/- 29 mm Hg min/ml, SE) than in normal human cadaveric femora (14 +/- 6) and was also higher in subcapital (253 +/- 39) than intertrochanteric sites (78 +/- 17). HR correlated highly with baseline intraosseous pressure (r = 0.74, p less than 0.001). HR testing is a simple, practical method which quantifies outflow obstruction of the intraosseous circulation. We believe this test will be helpful in the diagnosis of atraumatic osteonecrosis and in the understanding of its underlying pathophysiology. PMID- 3343633 TI - Viscous isoamyl 2-cyanoacrylate as an osseous adhesive in the repair of osteochondral osteotomies in rabbits. AB - An in vivo study of viscous isoamyl 2-cyanoacrylate used in limited amounts as an osseous adhesive was performed to evaluate the ability of the monomer to maintain the reduction of an unstable intra-articular osteochondral osteotomy as well as to allow for healing around the sites of adhesive placement. A histologic evaluation of any inflammatory reaction involving adjacent bone, cartilage, or synovium was also performed. Osteochondral fragments were created in 48 rabbit knees. In 24 knees, reduction of the fragment was secured with one small drop of adhesive at either end of the osteotomy surface. In 24 control knees, no adhesive was used. Ninety-six percent of the osteotomies in the adhesive treated group healed versus 50% of the control group. This difference is statistically significant (p less than 0.05). Osseous and cartilaginous healing was noted to proceed in an apparently unimpaired fashion around the sites of adhesive placement, and no inflammatory reaction involving adjacent viable tissue was evident. PMID- 3343634 TI - The influence of different degrees of stiffness of fixation plates on experimental bone healing. AB - In order to throw some light on the controversial issue of the optimal stiffness in fracture fixation, the effects on bone healing of rabbit tibial osteotomies fixed by plates with four different degrees of stiffness were studied. The least stiff plate was made of glass fiber-reinforced epoxy; the other three were made of stainless steel. The median bending stiffness in vitro of tibial osteotomies fixed with the various plates were 13%, 17%, 61%, and 74%, related to the stiffness of intact tibiae. Transverse midshaft unilateral tibial osteotomies were fixed by the various plates, and the animals were killed after 6 weeks. The amount of periosteal callus was inversely related to the stiffness of the plates. A marked trend toward decreased strength and stiffness occurred in tibiae where the most rigid plate was used, compared with the values of those with the less rigid plates. This indicates that the stress-protecting effect of very stiff plates begins early in the healing period and is pronounced even at 6 weeks and that a steel plate of lower stiffness is more appropriate for bone healing. However, too flexible plates involve increased risk of redislocation and mechanical failure. PMID- 3343635 TI - Congenital glaucoma associated with cutis marmorata telangiectatica congenita: two case reports. AB - Two cases of cutis marmorata telangiectatica congenita are described in association with nevus flammeus and congenital glaucoma. Approximately 65 cases have been reported and the association with nevus flammeus and congenital glaucoma has only been reported in one of those cases. Unlike the glaucoma associated with nevus flammeus of Sturge-Weber, this type of congenital glaucoma appears to be associated with an abnormal filtration angle rather than an increased episcleral venous pressure. PMID- 3343637 TI - Accommodation in school children with music or sports activities. AB - The accommodation of 324 school children aged 10 to 16 years was studied before and after a 12-minute reading session. One hundred and twenty children (81 girls and 39 boys) were wind instrument players in school bands, 93 children (48 girls and 45 boys) trained in an individual sport, and 111 children (65 girls and 46 boys) having no such activities were studied as a control group. At the end of the reading session, decreased accommodation (7 diopters or less) was found in 19 (15.8%) of the musicians, in six (6.5%) of the athletes, and in six (5.4%) of the control group. The difference was significant between the musicians and the control group, but not significant between the athletes and the control group. The majority of the children with low accommodation were girls; there was only one boy with decreased accommodation in each of the three groups. PMID- 3343636 TI - Goniotomy with sodium hyaluronate. AB - A modification of the classical goniotomy technique is described. After complete evacuation of the anterior and posterior chambers, sodium hyaluronate is placed in the anterior chamber and on the cornea. Putting hyaluronate in both locations prevents the formation of air bubbles under the goniotomy lens, provides the same index of refraction on both sides of the cornea, prevents accidental loss of the anterior chamber, and allows maximal depth of the anterior chamber. Diminished intraocular bleeding and lower risk of injury to the corneal endothelium, iris, and lens may be additional advantages of the procedure. Two cases are presented in which five goniotomies were performed on four eyes using this technique. Both patients had one eye controlled with a single goniotomy. The fellow eye of each patient required multiple procedures. Glaucoma was controlled successfully with no medication in all four eyes. No significant complications occurred. PMID- 3343639 TI - Horner's syndrome in children. AB - Ten cases of Horner's syndrome with pharmacologic testing and computed tomography scans are described in patients up to age 8 years. The patients also were assessed for iris color and facial sweating. Classical preganglionic Horner's syndrome associated with brachial plexus birth injury was not identified in any case. Two patients who presented with ptosis had neuroblastoma. Two other children had undergone corrective cardiothoracic surgery. Two patients had major congenital abnormalities. In four patients, no cause of Horner's syndrome was determined. PMID- 3343638 TI - Congenital toxoplasmosis presenting as isolated acute chorioretinitis in the neonate. AB - We describe a neonate with congenital ocular toxoplasmosis that presented as isolated, acute bilateral retinochoroiditis. Although toxoplasmic retinochoroiditis is not rare, it is quite unusual to diagnose congenital toxoplasmosis based on isolated bilateral retinochoroiditis in an otherwise healthy neonate. Bilateral retinochoroiditis can be caused by syphilis, herpes virus, cytomegalovirus, and toxoplasmosis. Because specific treatments now exist for these conditions, it is important to establish proper diagnosis so that treatment can be initiated promptly. The differential diagnosis, work-up, and management of retinochoroiditis in the newborn is presented and discussed. PMID- 3343640 TI - The eyelid crease approach to superficial lateral dermoid cysts. AB - Although the traditional approaches to lateral orbital dermoids with incision directly over the lesion or camouflaged beneath the inferior brow provide good direct exposure of the lesion, the result may be cosmetically less acceptable due to prolonged erythema and ultimate depression of the scar when placed in the thicker skin of this region. The results in 11 patients in whom an eyelid crease incision was used are reported. Camouflage of the incision by the overlying lid fold resulted in very satisfactory cosmesis in the immediate postoperative period. The extremely thin lid skin in the crease resulted in rapid healing with a virtually imperceptible mature scar. With sufficient extension of the incision and undermining, the lid tissues could be displaced to allow adequate exposure and removal of the dermoid in all cases. PMID- 3343641 TI - Rate of deterioration in accommodative esotropia correlated to the AC/A relationship. AB - We analyzed the claim that accommodative esotropia tends to deteriorate with greater frequency if the accommodation convergence relationship (AC/A) is high. Records of 119 patients whose eyes were aligned with spectacles alone were studied. Their AC/A relationships were graded according to the difference between the distance and near measurements: normal included 0 to 9 prism diopters (delta) difference; grade 1 ranged from 10 to 19 delta difference; grade 2 from 20 to 29 delta difference; and in grade 3 the difference was 30 delta or greater. Deterioration is characterized by a nonaccommodative component of esotropia greater than 10 delta at distance becoming superimposed on the initial accommodative esotropia. Deterioration occurred in 7.7% of patients with a normal AC/A, 25% with grade 1 high AC/A, 44% with grade 2 high AC/A, and 52% with grade 3 high AC/A. Hypotheses were investigated using chi square, t-test, analysis of variance (ANOVA), and log linear analyses. Distributional differences were highly significant by chi square test (p = 0.001) with a rejection of the null hypothesis of no difference between the groups at the alpha = 0.05 level. An alternate analysis of average AC/A ratio in the deteriorated versus nondeteriorated patients was equally statistically significant by the t-test. Hypermetropia was significantly higher in the normal AC/A group. Multi-factor comparisons showed that time-to-deterioration, treatment delay, age of onset, and amblyopia were factors that did not relate significantly to the incidence of deterioration. PMID- 3343642 TI - Children in pain: an underprivileged group. PMID- 3343643 TI - Hemobilia in childhood. AB - During a 10-year period we have encountered three cases of hemobilia among children after blunt abdominal trauma. All patients had the classical symptoms with varying degrees of severity. One of the patients, a 5-year-old boy, had several episodes of severe gastrointestinal bleeding, abdominal pain, and jaundice during a 2-month period. He was treated with selective arterial embolization of the left hepatic artery. The symptoms ceased instantly, and the patient has remained healthy during an observation period of more than 2 years. In cases of hemobilia, selective arterial embolization is a safe method with no serious complications. Arterial collaterals develop very quickly and the risk of liver dysfunction is small. We suggest that embolization of hepatic arteries may be the treatment of choice even in small children with hemobilia. PMID- 3343644 TI - Management of pancreatic pseudocysts in children. AB - The management of 25 children with pseudocyst of the pancreas presenting over a 30-year period is reviewed. Nearly a third could be managed nonoperatively, monitoring clinical signs, serum amylase, and in recent years the findings of ultrasound and CT scan. Persistence of symptoms, signs, and hyperamylasemia for more than 4 weeks indicated failed resolution in all but one case. Endoscopic retrograde cholangiopancreatography (ERCP) done in those who did not improve spontaneously facilitated operative strategy. Early operation and internal drainage in selected cases was well tolerated. Individualization of treatment is emphasized. PMID- 3343645 TI - Does the spleen regenerate after partial splenectomy in the dog? AB - Four dogs underwent two thirds partial splenectomy and the remaining spleens were followed up to 6 months by radioisotope studies and finally measured at the time of sacrifice. In this study we showed that the remaining spleens after partial splenectomy did not show any signs of regeneration. PMID- 3343646 TI - Umbilical gangrene in the newborn. AB - Six neonates are described with a gangrenous omphalitis, a disease not reported for many years. They had many features in common including previous good health. In two, the disease was preceded by the application of tobacco ash to the umbilical stump. Clinically there was gangrene of the umbilicus with a blood stained discharge and extensive cellulitis radiating into the abdominal wall. Despite aggressive therapy including excision of the affected area, the systemic effects of the local disease progressed rapidly until all of the first five infants who presented, died. Microbiologically there was a polybacterial infection involving a wide variety of organisms particularly E coli and Clostridia species. There appeared to be an appropriate response by the infants to an acute bacterial infection, and two patients investigated showed no evidence of cellular or humoral immunodeficiency. The pathology was an infection causing local tissue necrosis with a vasculitis and microabscess formation, which involved adjacent structures by direct extension. The severe systemic symptoms were attributable to an endotoxemia or exotoxemia. The evolution of therapy for gangreneous omphalitis in the newborn, successful in the sixth patient, is discussed. PMID- 3343647 TI - Prognostic factors in neonatal intestinal obstruction: a prospective study of Nigerian newborns with bowel obstruction. AB - The management of neonatal intestinal obstruction in developing countries remains challenging, but the results are relatively less rewarding compared with results of treatment of this condition in industrialized countries. This study is an attempt to evaluate, using acceptable scientific methods, some of the factors that are believed to influence survival in neonatal intestinal obstruction, including those that are not peculiar to developing countries alone. Sixty-five babies treated for intestinal obstruction at the Lagos University Teaching Hospital, Lagos, Nigeria, formed the subjects for the study. The levels of obstruction, which were congenital in all cases, spanned the entire intestinal tract from the duodenum to the anus. Forty-one babies survived and 24 died, a survival rate of 63%. Employing Student's t test, there were no significant differences in the gestational age and birth weight between survivors and nonsurvivors, whereas significant differences do exist with respect to the age at operation and admission serum bicarbonate levels, P less than .05 and P less than .001, respectively. Analysis of the levels of obstruction and nature of operative procedure using the chi-square test shows no significant differences between the two groups. However, there is significant difference in the percentage of major associated congenital problems, P less than .01, which was higher in nonsurvivors. PMID- 3343648 TI - Endoscopic balloon dilatation as treatment of gastric outlet obstruction in infancy and childhood. AB - The application of balloon dilatation as treatment of gastric outlet obstruction is described. In two infants after inadequate pyloromyotomy and in an 11-year-old boy with surgical damage to the vagus, balloon dilatation was successful and considered a good alternative to surgery in these conditions. PMID- 3343649 TI - Sphincteromyectomy and sphincteroplasty in chronic constipation with megarectum. AB - An operative procedure for patients with chronic constipation with megarectum and its results is presented. Eleven cases of idiopathic chronic constipation showing megarectum on barium enema underwent this operation. Bowel habits of operated patients were evaluated at 1 to 5 years after the operation. Complete cure was obtained in eight cases. Three cases were improved but needed occasional suppositories. This procedure, sphincteromyectomy and sphincteroplasty, may be an operation of choice for chronic constipation with megarectum, when nonoperative methods fail. PMID- 3343650 TI - A method for recovering a lost retrieval line under direct vision in children with esophageal strictures. AB - Loss of a retrieval line for repeated esophageal dilations for caustic esophageal stricture may result in inability to dilate these strictures. We describe a simple means for retrieving such a line once it has been removed. PMID- 3343651 TI - Surgical management of ureteroceles in children: strategy based on the classification of ureteral hiatus and the eversion of ureteroceles. AB - Experience in the surgical management of ureteroceles in children is reported. Six patients with intravesical and 16 with ectopic ureteroceles are included. In the case of intravesical ureterocele of noneverting type. Transurethral distal incision of the ureterocele was performed without reflux. In the case of everting ureterocele, excision with reimplantation of the ureter was performed, thus avoiding reflux inevitably induced by transurethral incision. In the patient with an ectopic ureterocele, a one-stage operation with complete excision of the ureterocele and ureteral stump was attempted. Our choice of operative procedure was decided after the assessment of the following features: cystography and cystoscopy to assess eversion, type of ureteral hiatus (common or separate), whether there was reflux or not to the ipsilateral ureter, and renal function by scintigraphy. Accordingly, hemi-nephroureterectomy or twin ureteroneocystostomy were most commonly performed. When based on these thorough preoperative evaluations, our results were quite favorable. PMID- 3343652 TI - Embryology of bladder exstrophy. AB - A hypothesis in respect to the teratogenesis of bladder exstrophy and its variants is offered. The central feature of this hypothesis is the abnormal persistence of the caudal position of the insertion of the body stalk on the embryo. As a consequence of this, the normal advance and interposition of mesenchymal tissue to the midline becomes impossible. The cloaca cannot be translocated backwards into the body cavity, and the cranial end of the cloacal membrane remains in contact with the inferior aspect of the low-set body stalk. This, in contrast to the previously proposed abnormal rostral extension of the cloacal membrane, causes a wedge-effect resulting in the lateralization of the abdominal wall structures and also in the prevention of the midline fusion of the genital hillocks (labioscrotal or genital folds). A cloacal membrane normally is an unstable structure lacking mesoderm, and it retains these characteristics in the superficial and infraumbilical position to be described. It has a strong tendency to disintegrate. It may rupture at variable times and to a variable extent. The consequence of such an embryonic event is either a typical bladder exstrophy or one of the variants of the exstrophy malformation. Three different variants are presented that the proposed embryologic hypothesis can readily explain. PMID- 3343653 TI - Treatment of iatrogenic functional or morphologic bladder loss. AB - From 1984 to 1986, six children from 4 to 13 years of age, received a bladder augmentation by ileocecal cystoplasty (Mainz-pouch technique) because of an iatrogenic functional or morphologic bladder loss. Indications for operation were incontinence due to the low bladder capacity or threat to the upper urinary tract due to ureteral obstruction or vesicorenal reflux. Two of the children had already undergone supravesical urinary diversion by sigmoid conduit. After a follow-up period of 2 to 19 months, (mean 11 months), five of the six children are completely continent. One boy with a known weak sphincter still has slight, but decreasing, enuresis nocturna in periods of complete filling of the pouch, 1 month after the operation. All children are able to void their augmented bladders without residual urine. PMID- 3343654 TI - One-stage total repair of severe hypospadias with scrotal transposition: experience in 18 cases. AB - This is a report detailing further experience with our one-stage repair of severe hypospadias and scrotal transposition performed on 18 patients. Initial success was obtained in 12 cases, while two more were improved by secondary repair. The operative technique, as modified, assures a parameatal preputial flap, which is well vascularized and easily constructed into a neourethra. The advantages of this improved "glanulomeatoplasty" and scrotoplasty are discussed. The method is recommended as an excellent functional and cosmetic procedure for one-stage correction of severe hypospadias. PMID- 3343655 TI - Management of the penile shaft skin in hypospadias repair: alternative to Byars' flaps. AB - Two variations for resurfacing the penile shaft skin after repair of hypospadias defects are described. These techniques have been used in an effort to prevent some of the skin tags, tension at the penoscrotal angle, and oblique suture lines that may occur with the traditional Byars' flaps. PMID- 3343657 TI - I challenged the State Nurses Association. PMID- 3343656 TI - Combination of annular pancreas and partial situs inversus: a multiple organ malrotation syndrome associated with duodenal obstruction. AB - A combination of annular pancreas and partial situs inversus has been encountered in three babies who presented as duodenal obstruction. All the abnormalities can be explained on the basis of multiple organ malrotation involving the duodenum, pancreas, liver, stomach, and indirectly, the spleen; hence, the term multiple organ malrotation syndrome (MOMS). The heart maintains its normal left side location in this condition. Similarly the remaining small bowel, large bowel, and appendix are normally located. It is proposed that the triad of intestinal obstruction as suggested by vomiting and visible peristalsis, left-sided liver in the presence of laevocardia, and radiographic appearance of reversed double bubble, be considered as indicating MOMS. PMID- 3343658 TI - How it was: frank recollections of nursing in Africa. PMID- 3343659 TI - Abused--a nurse's journey out of a nightmare. PMID- 3343660 TI - Surface tendon force measurements in determining muscle contraction properties. PMID- 3343661 TI - Radiographic anatomy of the calcaneus. Part IV: Lateral and medial surfaces. PMID- 3343662 TI - Screening for the pedal manifestations related to chemical abuse. PMID- 3343663 TI - A comparison of three positions used to evaluate tibial varum. PMID- 3343664 TI - Osteotomy of the proximal phalanx with lag screw fixation. PMID- 3343665 TI - Use of C-reactive protein to predict the outcome of medical management of tuboovarian abscesses. AB - Medical management of tuboovarian abscesses (TOAs) has been shown to be successful. However, the ability to predict which patients with TOA would respond to antibiotic therapy could shorten the hospital stay and decrease treatment costs. C-reactive protein (CRP), an acute-phase-reactant protein with a short half-life, was investigated as a possible predictor of response by TOA patients to medical therapy. Twenty-two patients with TOAs were admitted prospectively into this study, which included daily quantitative determinations of CRP. The patients had either resolution of the mass and symptoms (responders), increased evidence of systemic sepsis and acute peritonitis requiring surgery (failures) or continuation of the tender adnexal mass without evidence of peritoneal irritation (persisters). Twelve patients classified as responders showed a continued daily decrease in quantitative CRP levels of at least 20% per day below the previous day's value until the return to normal levels. The five failures showed a progressive rise in CRP levels as well as evidence of systemic sepsis. Persisters showed an initial decrease in the CRP level followed by a leveling off of the value to a decrease of less than 20% per day. The rate at which daily CRP determinations decline may be a useful predictor of the response to antibiotic therapy. PMID- 3343666 TI - Treatment and prophylactic considerations in OB/GYN infections: a symposium. PMID- 3343667 TI - Ankle motion after external fixation of tibial fractures. AB - Loss of ankle movement is a complication of severe tibial fractures. This can be exacerbated if the foot is allowed to drop into equinus, particularly when an external fixator is employed. The range of ankle motion following external fixation of tibial fractures as compared to the opposite normal ankle was studied in 40 of 55 patients treated over a ten-year period. Nine were excluded due to other causes of ankle stiffness, leaving 31 cases for analysis. The mean follow up was 2 years 7 months (range 1 year to 8 years 3 months), and union had occurred by a mean of 35 weeks (range 9-100 weeks). The mean loss of ankle movement was 8 degrees of plantar-flexion and 12 degrees of dorsiflexion (overall loss 20 degrees), the difference between the two being highly significant (P greater than 0.001, t test). Loss of ankle motion closely paralleled the degree of soft tissue trauma, being 6 degrees for closed fractures and 22 degrees for open fractures (0.05 greater than P greater than 0.02). Ankle function is therefore at risk when a severe tibial fracture is treated by external fixation, and appropriate measures should be taken to preserve movement and prevent an equinus contracture. PMID- 3343668 TI - Fertile mules. PMID- 3343669 TI - The anion gap as a screening procedure for occult myeloma in the elderly. AB - Myeloma in the elderly can mimic many disorders, causing delay in diagnosis. In a retrospective study, the mean anion gap at presentation in 78 elderly patients with confirmed myeloma was found to be significantly less than that of aged matched controls. It is suggested that estimation of the anion gap may be useful as a screening test, particularly as it has no intrinsic cost. PMID- 3343670 TI - Social work and primary care--the need for increased collaboration: discussion paper. PMID- 3343671 TI - The invaluable art of unlearning. PMID- 3343672 TI - Fluctuating thyroid dysfunction following irradiation of the neck for the treatment of Hodgkin's disease. PMID- 3343673 TI - Compensated autoimmune adrenocortical insufficiency. PMID- 3343674 TI - Severe cardiac failure and leukoerythroblastic anaemia in a patient with giant cell arteritis. PMID- 3343675 TI - Osteomyelitis with a rapidly fatal course. PMID- 3343676 TI - Hyperthyroidism in pregnancy. PMID- 3343677 TI - Antiphospholipid antibody syndrome. PMID- 3343678 TI - Diaphragm weakness and syringomyelia. PMID- 3343679 TI - Reoperative surgery for early complications following abdominal and abdominothoracic operations. AB - In-hospital mortality was 9.6% in 3000 abdominal and abdominothoracic operations carried out by me or under my care. Intra-abdominal complications developing during the recovery period required reoperation in 141 patients. The decision to reoperate was a clinical one in 97.8%, although investigations were often helpful in localizing the site of the complicating lesion: the mortality in this group was 42.5%. Technical failure at the first operation could be indicated in 46%. Leaks and bleeding were most frequent and carried a high mortality. Patient selection and preparation, and selection of the simplest effective procedure, are not yet capable of being fully assessed in an individual patient. PMID- 3343680 TI - Transmission of human immunodeficiency virus infection. PMID- 3343681 TI - AIDS in the workplace. PMID- 3343682 TI - Radiologic seminar CCXLIX: growing skull fractures of childhood. PMID- 3343683 TI - AIDS crisis challenges medical profession. PMID- 3343685 TI - Testing for HIV infection. PMID- 3343684 TI - Incidence of AIDS and prevalence of HIV in Mississippi. PMID- 3343687 TI - Autocrine growth of murine lymphoma cells. AB - By using an assay system in which small numbers of murine T lymphoma cells are stimulated to grow in serum-free medium, we have continued and expanded our previous studies of an autocrine growth factor that we call leukemia-derived growth factor (LDGF). We show that a T lymphoma cell line of immature phenotype, adapted to growth in serum-free medium, produces and responds to LDGF. LDGF activity is distinct from activities of 10 highly purified or recombinant hematopoietic growth factors including IL-1 and IL-2. However, growth-stimulating activity for the murine lymphoma cells is provided by a partially purified human LDGF. PMID- 3343686 TI - Metastasis inhibition of different tumor types by purified laminin fragments and a heparin-binding fragment of fibronectin. AB - Tumor cell metastasis is a complex process that depends in part on tumor cell adhesion to components of basement membranes and the extracellular matrix. Previous studies have indicated that the experimental metastasis of murine melanoma cells can be inhibited by ex vivo pretreatment of cells with purified adhesion-promoting fragments of laminin or the synthetic peptide arginyl-glycyl aspartyl-serine (RGDS) prior to tail vein injection. This study extended the earlier reports to demonstrate that adhesion-promoting fragments of laminin and fibronectin can inhibit the metastasis of a tumor of different histologic origin, such as murine fibrosarcoma cells. Furthermore, ex vivo pretreatment of cells with a purified 33-kDa heparin-binding fragment of fibronectin, which promotes tumor cell adhesion by an RGDS-independent mechanism, was effective at inhibiting experimental melanoma and fibrosarcoma pulmonary metastases. The survival rate of animals receiving tumor cells pretreated with this fragment was significantly enhanced relative to control groups. As with previous studies, the mechanism of inhibition appeared to involve an increased clearance rate of tumor cells from the pulmonary microcirculation. These results suggest a role for cell surface proteoglycans in the adhesion and metastasis of certain malignant neoplasms. Furthermore, this study emphasizes the complexity of tumor metastasis and suggests that multiple strategies may be developed to inhibit hematogenous metastasis formation. PMID- 3343688 TI - Vitamin A, beta-carotene, and the risk of cancer. PMID- 3343689 TI - Whither screening for lung cancer? PMID- 3343690 TI - The tobacco subsidy: does it matter? PMID- 3343691 TI - Multiple markers for lung cancer diagnosis: validation of models for localized lung cancer. AB - Sera from 71 patients with localized lung cancer, from 70 normal controls, and from 73 patients with benign lung diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2 microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen (CEA). Individual markers were studied, and optimal combinations of markers were sought for discriminating patients with localized lung cancer from normal controls and from patients with benign lung disease. Both logistic regression and recursive partitioning methods for discrimination were tried. The best rules involved only CEA and ferritin for discriminating patients with lung cancer from normal controls, and CEA and age for discriminating patients with lung cancer from those with benign lung diseases. The performance of these rules was validated on an independent serum panel containing sera from 56 patients with localized lung cancer, 75 normal controls, and 75 patients with benign lung diseases. Three rules designed to achieve 95% specificity against normal controls attained 14%-36% sensitivity for localized lung cancer in the validation panels, whereas three rules designed to achieve 95% specificity against benign lung diseases attained 30%-39% sensitivity. Some aspects of potential clinical applications are discussed. PMID- 3343692 TI - Studies of acute nephrotoxic potential of trichloroethylene in Fischer 344 rats. AB - Group of male Fischer 344 rats, after pretreatment with phenobarbital (80 mg/kg, ip, 3 d), were treated ip in corn oil with 0, 5.5, 11.0, and 22.0 mmol trichloroethylene (TRI) per kg body weight. Urines were collected 24 h after the treatment and the animals were then sacrificed. The nephrotoxicity of TRI was then studied by measuring certain biochemical parameters characteristic of renal injury and its in vivo metabolism by quantitating the TRI principal urinary metabolites. Treatment of rats with TRI up to 11 mmol/kg did not influence any of the measured biochemical parameters of nephrotoxicity. On the other hand, significant increases in the urinary level of N-acetyl-beta-glucose-D-aminidase (NAG) and glucose as well as serum urea nitrogen were observed at 24 h only at the highest dose level (22 mmol/kg) or TRI. Urinary excretions of both trichloroethanol and trichloroacetic acid reached an apparent saturation at the highest dose level of TRI. In inhalation studies, urinary levels of gamma glutamyltranspeptidase, NAG, glucose, proteins, and serum urea nitrogen were significantly increased at 24 h when rats were exposed to either 1000 or 2000 ppm TRI for 6 h. The capacity of renal cortical slices to accumulate p-aminohippurate was significantly reduced 24 h after the exposure to 22 mmol TRI/kg (ip), or to 1000 or 2000 ppm TRI. These results have demonstrated that TRI exerts its acute nephrotoxic potential at a very high dose level and produces nephrotoxic insult at the proximal tubular and possibly glomerular regions of the rat kidney, whether exposed by inhalation or by an ip route. These data further indicate an involvement of a capacity-limited metabolism in the expression of acute nephrotoxicity due to TRI in Fischer 344 rats. PMID- 3343693 TI - Role of glutathione in the toxicity of the sesquiterpene lactones hymenoxon and helenalin. AB - Hymenoxon and helenalin are toxic sesquiterpene lactones present in the toxic range plants Hymenoxys odorata and Helenium microcephalum. Helenalin (25 mg/kg) or hymenoxon (30 mg/kg) administered to immature male ICR mice caused a rapid decrease in hepatic glutathione levels and were lethally toxic to greater than 60% of the animals within 6 d. L-2-Oxothiazolidine 4-carboxylate (OTC), a compound that elevates cellular glutathione levels, administered to mice 6 or 12 h before either helenalin or hymenoxon protected against hepatic glutathione depletion and the lethal toxicity of these toxins. OTC administered at the same time as the sesquiterpene lactones was not protective, suggesting that the critical events against which glutathione is protective occur within the first 6 h. In primary rat hepatocyte cultures, hymenoxon and helenalin (4-16 microM) caused a rapid lethal injury as determined by the release of lactate dehydrogenase. Cotreatment of cultures with N-acetylcysteine at high concentrations (4 mM) afforded significant protection against lethal injury by both toxins. In contrast, BCNU, which inhibits glutathione reductase, or diethylmaleate, which depletes hepatocellular glutathione, potentiated the hepatotoxicity of helenalin and hymenoxon in monolayer rat hepatocytes. These studies suggest that the in vivo and in vitro toxicity of hymenoxon and helenalin is strongly dependent on hepatic glutathione levels, which hymenoxon and helenalin rapidly deplete at very low concentrations. PMID- 3343694 TI - Tissue levels of glutathione following acute inhalation of 1,3-dichloropropene. AB - Rats were exposed by inhalation to 1,3-dichloropropene (DCP) to assess the relationship between DCP exposure concentration and tissue levels of reduced glutathione (GSH). Animals were exposed for 1 h in a dynamic, nose-only system. GSH content, indicative of DCP metabolism, was measured in heart, kidney, liver, lung, nasal mucosa, and testes. A decrease in nasal GSH content was first seen at 5 ppm DCP and followed an exposure concentration-dependent curve. Exposure to concentrations above 305 ppm DCP reduced the level of liver GSH in an exposure concentration-dependent manner. Although depressed, lung GSH content remained relatively constant at approximately 75% of control following concentrations of up to 955 ppm DCP. Significant decreases in GSH content were observed in heart, liver, and testes only at 1716 ppm. Additional measurements were taken to investigate DCP distribution and potential indicators of acute toxicity. DCP was not present in the blood of animals 2 h after exposure to 955 ppm DCP or less. Serum lactate dehydrogenase activity was affected only at the highest exposure concentration, 1716 ppm DCP. Lung weight, measured at 2 and 6 h after exposure, did not differ from control for any of the exposure levels. This information demonstrated the importance of nasal tissue GSH in the metabolism of at least low levels of DCP. It also suggests the complexities involved with in vivo defence against inhaled DCP. PMID- 3343695 TI - Studies on the mechanism of the acute and carcinogenic effects of N nitrosodimethylamine on mink liver. AB - Outbreaks of liver necrosis and liver hemangiosarcoma were detected in a mink breeding colony in Argentina. Analysis of the Minks' food revealed the presence of 2.6 ppm dimethylnitrosamine (NDMA) in it, apparently as a result of the addition of nitrite as preservative. Previous studies gave evidence of the particular susceptibility of minks to NDMA and other hepatic insults. We have determined several biochemical parameters known to correlate with NDMA hepatotoxic effects and compared them with those in rat liver. NDMA administration to both species resulted in the formation of reactive metabolites able to interact with liver DNA to give N7-methylguanine and O6-methylguanine adducts. Biotransformation of NDMA by liver slices to CO2 was significantly lower in the mink than in the rat, whereas the covalent binding (CB) to nucleic acids was slightly lower than in in the rat. Aminopyrine N-demethylase activity was also significantly less in mink than in rat liver. The CB of NDMA reactive metabolites to microsomal proteins was not significantly lower in mink as compared to the rat, and the same holds true for the biotransformation of NDMA to formaldehyde by microsomal preparations. Results suggest that the high susceptibility of minks to NDMA might be partially due to a decreased ability to detoxicate NDMA but also to a higher intrinsic susceptibility of their liver cells to a given chemical insult. PMID- 3343696 TI - Dermal toxicity of a medium-boiling (154-378 degrees C) coal liquefaction product in the rat--Part I. AB - The subchronic dermal toxicity of a medium-boiling coal liquefaction product (CLP, 154-378 degrees C) was investigated in the rat. CLP was applied to the shaved backs of rats at dose levels of 50, 100, 200, or 400 mg/kg body weight.d, 7 d/wk for a period of 13 wk. Control groups received 0.4 ml/kg of normal saline. Signs of dermal irritation were observed at sites of application in males dosed at 200 and 400 mg/kg body weight and were characterized by thickened, focally necrotic and ulcerative skin. All animals survived the full length of the treatment period. Growth depression was observed in males at all dose levels, but no significant decrease in weight gain was observed in females. An increase in liver/body weight ratios was observed in all treatment groups of both sexes. The organ/body weight ratios for the spleen, heart, kidney, and brain were also increased in the upper dose groups of both sexes. Treatment with CLP caused a dose-dependent decrease in hemoglobin and packed cell volume in both sexes of all dose groups. The number of erythrocytes was decreased and that of neutrophils was increased in some CLP-treated groups of both sexes. There was a mild myeloid hyperplasia with increased myeloid/erythroid ratios in the 200- and 400-mg/kg groups of both sexes. Hepatic microsomal ethoxyresorufin deethylase activity was increased in all treatment groups of females, and in males dosed at 100 mg/kg and higher. In the renal tubules mild treatment-related histological changes occurred, which consisted of eosinophilic inclusions, increased cytoplasmic volume, and pyknosis. These changes were noted in the high-dose groups of both sexes. These data indicate that the medium-boiling CLP could produce systemic toxicity when applied dermally at 50 mg/kg body weight.d. PMID- 3343697 TI - Percutaneous absorption of cis- and trans-permethrin in rhesus monkeys and rats: anatomic site and interspecies variation. AB - Dermal absorption of cis- and trans-permethrin isomers was determined in rhesus monkeys and Sprague-Dawley rats. Four 14C radiolabels were used (cis alcohol, cis cyclopropyl, trans alcohol, and trans cyclopropyl). One microcurie of each radiolabel was applied to either the forehead or forearm of rhesus monkeys or to the midlumbosacral region of the rat. Urine was collected for 7 or 14 d. Correction factors for incomplete urine excretion were derived from measurements of radiolabel in the urine following im injection of an equivalent dose. It was noted that the total im dose recovered in the urine of both species was lower for the cis isomer than for the trans isomer. There was no significant difference between the dermal absorption of the cis isomer and that of the trans isomer in monkeys. The forehead, however, was more permeable for both isomers than the forearm (alcohol- and cyclopropyl-labeled cis and trans isomers, respectively, showed permeation in forehead, cis 28 +/- 6%, 24 +/- 6%, trans 21 +/- 3%, 14 +/- 4%, forearm, cis 9 +/- 3%, 9 +/- 3%, trans 12 +/- 3%, and 5 +/- 2%). There was no difference between absorption of the isomers (cis 46 +/- 4%, trans 43 +/- 5%) in rats, but absorption was significantly greater than in monkeys. The IM urinary t1/2 values in monkeys and rats were similar for both isomers (0.8-1.1 d). PMID- 3343698 TI - Pulmonary function in juvenile and young adult rats exposed to low-level NO2 with diurnal spikes. AB - Pulmonary function was examined for juvenile and young adult Fischer 344 rats that were continuously exposed to NO2 (0.5, 1.0, or 2.0 ppm) for up to 6 wk. The exposure included twice daily 1-h spikes equal to 3 times the baseline concentration. This spike-to-baseline ratio was chosen to simulate morning and evening urban rush-hour conditions. Juvenile rats were examined after 3 and 6 wk of NO2 exposure, whereas young adult rats were examined after 1-, 3-, and 6-wk intervals. Lung volumes, compliance, and efficiency of ventilation distribution were evaluated. Lung volumes increased in the juvenile rats after 3- and 6-wk exposures to 1.0 and 2.0 ppm NO2, but were unchanged in young adult rats. Lung compliance increased in juvenile rats exposed to 1.0 or 2.0 ppm NO2 for 3 wk. However, it was unchanged in juvenile rats exposed for 6 wk or in young adult rats exposed for 1 or 3 wk. Compliance decreased in young adult rats exposed to 2.0 ppm NO2 for 6 wk and was correlated to an overall thickening of alveolar interstitium and septal tissue. However, the observed changes in pulmonary function were marginal and reversible, since lung-function measurements were not different from controls after a 3-wk recovery period. PMID- 3343699 TI - Toxicity of inhaled cadmium chloride: early responses of the antioxidant and surfactant systems in rat lungs. AB - In order to establish an animal model for assessing early and sensitive biochemical indicators of pulmonary damage, we studied the effects of inhaled CdCl2 (5 mg/m3.h; mass median aerodynamic diameter (MMAD) = 1.4 microns; SDg = 1.8) on the antioxidant defense and pulmonary surfactant systems of rat lungs. Rats were sacrificed 1, 4, 8, and 16 d after inhalation. Pulmonary edema (wet/dry weight) was observed on d 1. The total activities of the enzymes superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G6PD) in the lung homogenates of the treated animals were significantly throughout the 16-d period. Glutathione reductase (GR) was increased on d 4 and after. The general increases of SOD, GR, and the lysosomal enzymes acid phosphatase and beta-N acetylglucosaminidase could be attributed to changes in the cellularity of the lung tissue. The significant increase in the specific activity of G6PD on d 4 suggested enzyme stimulation. Concurrently, the response of the surfactant system was measured by assaying the alkaline phosphatase (AKP) and the phospholipid content in the homogenates and in the cell-free bronchoalveolar lavage (BAL) fluids. The AKP activity in the homogenates decreased by 30%, while no activity was detected in the BAL on d 1, suggesting an inhibition of AKP by Cd. The secretion of surfactant seemed altered at this early time: phospholipid in the BAL decreased by 44%, although it increased by 61% in the tissue. The high recovery of phospholipid (312%) in the BAL on d 4 and the important changes in the AKP activity in the BAL from d 4 to 16 may reflect alterations in the processing of the surfactant. The effect of Cd on AKP makes this enzyme a potential marker of the metal redistribution in the pulmonary alveolar region, which could be a useful tool in long-term studies. PMID- 3343700 TI - Effects of lead on viability and intracellular metal content of C6 rat glioma cells. AB - Cultured C6 rat glioma cells were exposed to lead (Pb) acetate (0, 1, 10, or 100 microM) for 3-4 d. Cells were analyzed for changes in viability and intracellular lead, iron, and copper concentrations after Pb treatment was discontinued. The results were compared with previous findings on astroglia and oligodendroglia in culture in order to evaluate C6 cultures as a model for Pb toxicity in glia. Viability was measured by three methods on the day Pb was removed from the cells (designated d 0), and 2 and 9 d after Pb treatment was discontinued (designated d 2 and 9). The methods used were trypan blue dye exclusion, total cell counts, and incorporation of [3H]-L-leucine into proteins. Small, dose-dependent reductions were observed on d 2 in the percentages of cells excluding dye. Decreased cell numbers were seen at all three Pb doses only on d 0. With respect to these two viability measurements, C6 cells responded like astroglia in culture to Pb, but not like oligodendroglia, which are more Pb-sensitive. We expected decreased amino acid incorporation to accompany the decreased viability of the cultures. Instead, increased amino acid incorporation, which indicates increased protein synthesis, was seen on d 0 and 2 at all three Pb doses, though total cellular protein did not increase. A similar response has been reported previously in oligodendroglial cultures. C6 cells treated for 3 with 1 or 100 microM Pb acetate were analyzed for intracellular metal content by atomic absorption aspectroscopy on d 4 and 11 after exposure to Pb was discontinued. The cells were found to take up large amounts of Pb intracellularly and store it for at least 11 d. Cells treated with FeCl2 instead of Pb took up Fe, but required a higher extracellular Fe concentration to achieve an intracellular Fe level comparable to that of Pb in Pb-treated cells. Pb uptake did not affect intracellular Fe or Cu concentrations. With respect to Pb and Fe uptake, C6 cells closely resembled immature astroglia in culture. Unlike C6 cells, however, astroglia showed elevations of intracellular Fe and Cu after Pb treatment. Thus, Pb effects on C6 cells resembled those on cultured oligodendroglia and astroglia in some respects but not in others. C6 cells appear to be an adequate model for selected events in glial toxicosis, such as Pb-stimulated protein synthesis in oligodendroglia and Pb uptake in astroglia, but not Pb-induced alterations of intracellular Cu and Fe in astroglia. Their use as a model for glial progenitor cells in Pb toxicity studies remains to be determined. PMID- 3343702 TI - Development of the amino acid pools in chick embryo brain, heart, and eye: taurine, valine, glutamine, and phosphoethanolamine. AB - The redistribution of valine, from the nonrenewable yolk supply into excitable tissues, was studied during the first 15 days of chick embryogenesis. Valine levels in the extraembryonic circulation (the vitelline plexus) peak between days 7-9 (E7-9) and then decline steeply. In their first phase of differentiation (E2 E4), all embryonic tissues contain more valine than the blood plexus. From E4 to E7, the heart and brain exhibit initially a rapid fall in valine, but from day 7 on the decrease becomes more gradual. The eye during the same period reaches an equilibrium with circulating valine; as these levels fall from E9 to E15, the eye retains the valine that accumulated. Against this pattern of change, characteristic for an essential amino acid during embryogenesis, glutamine levels are at any time from two- to threefold higher than valine in all tissues. In the circulation, this ratio remains constant throughout the 15 days of embryonic development. Eye glutamine, higher on day 4, by E7 has entered into an equilibrium with glutamine in the plexus. A steady but two times higher glutamine level is maintained in the heart, although during the later stages of development it gradually tends to approach the plexus content. In sharp contrast, starting on E7 and accelerating on E9, a large increase of glutamine relative to valine or other essential amino acids is seen in developing brain tissue. This appears typical for most metabolic amino acids, suggesting that by days 9-10 the essential amino acid supply in the brain is being exhausted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343701 TI - Methods to study changing free amino acid pools during embryonic chick development. AB - During early embryogenesis of the chick, the yolk represents the only source of free amino acids. Leucine and glutamic acid, together with valine, predominate in this nonrenewable nutrient supply; taurine and phosphoethanolamine are present in the lowest concentration. The tyrosine level is already twice as high as phenylalanine. At embryo day 2 (E2), the not-yet fully functioning vitelline blood plexus demonstrates an amino acid profile that rather closely resembles that of the yolk, except for three amino acids. During the transfer process from yolk to plexus, a certain amount of glutamic acid appears to be metabolized to glutamine and aspartic acid. Taurine and phosphoethanolamine are highly concentrated in the circulation, with a ten-fold increase of taurine and a 50 fold rise in phosphoethanolamine. The tyrosine-to-phenylalanine ratio remains 2:1, but their levels relative to valine and other essential amino acids fall by roughly 50%. In the already contracting heart tube and the developing neural tissue on E2, taurine and phosphoethanolamine also accumulate preferentially; the levels in neural tissue are ten- and fivefold higher than in the circulation for the respective amino acids, whereas the heart has three time the plexus content of taurine and two times the amount of phosphoethanolamine. Tyrosine and phenylalanine, still in the same proportion, have risen to approximately twice the circulation values. The heart tube, unlike the primitive brain, concentrates leucine, whereas isoleucine accumulates in both organs. Injections of valine (50 mumol) and taurine (200 mumol) into the yolk on E1 demonstrate that a higher yolk content of an amino acid can result in a two- to threefold tissue increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343703 TI - The effect of the experimental antitumor agent caracemide on brain choline acetyltransferase. AB - Caracemide was found to inhibit choline acetyltransferase (CAT) from rat brain. A concentration of 0.5 mM caracemide inhibited the enzyme by 93%, whereas a degradation product from caracemide, N-(methylcarbamoyloxy)acetamide, produced only a 50% inhibition. Two other degradation products, N-(methyl-carbamoyloxy)-N' methylurea and N-hydroxy-N'-methylurea, lacked any inhibitory activity. With bovine brain CAT, caracemide showed noncompetitive inhibition with the substrate choline, Km 337 microM, Ki240 microM, Vmax 2.83 nmol acetylcholine formed/min/mg protein and mixed inhibition with the substrate acetyl-CoA, Km 21 microM, Ki 146 microM, Vmax 3.85 nmol acetylcholine formed/min/mg protein. PMID- 3343704 TI - Kinetic and pharmacologic characterization of dopamine binding in the mouse cerebellum and the effects of the reeler mutation. AB - The purpose of this study was to characterize the dopaminergic system in the mouse cerebellum and to determine whether the dyskinesia of the reeler mutant is accompanied by alterations in cerebellar and/or striatal dopamine binding. From the analysis of (3H) dopamine ((3H)DA) and (3H)spiperone ((3H)Sp) binding, the study of the effects of several drugs on this binding, and the comparison of these parameters between the cerebellum and striatum, we conclude that a dopaminergic system exists in the cerebellum with properties common to the striatal system but also with some differences. That is, 1) with (3H)DA as ligand, we find two binding sites in cerebellum with similar Kd to those of striatum but of lower density, 2) with (3H)Sp as ligand we observe two binding sites in cerebellum and one in striatum, and 3) the competition of (3H)DA binding by various drugs shows that among the cerebellar sites, relative to striatum, there is a higher proportion that corresponds to high affinity D3 and D4 (D2 high) binding sites. In cerebellum and striatum of reeler mice, (3H)DA binding increases 125-174% and 14%, respectively. PMID- 3343706 TI - Comparative effects of morphine on leukocytic antigenic markers of monkeys and humans. AB - Knowing the in vitro effects of morphine on monkey leukocytes would be helpful in extending the utility of a monkey model for psychoneuroimmunological investigations. Morphine effects on T11, Leu2a, and Leu3a antigenic markers on leukocytes from rhesus monkeys and humans were assessed by using single- and two color cytofluorometric analyses. Kinetics of expression of these markers was determined after modulation of the original complement of T11 markers from the surface of T11(+) cells. Percentages of leukocytes detectable by directly staining these markers before modulation were within the expected range for monkey and human cells. Also, as expected, T11 modulation reduced the percentages of cells expressing T11. This reduction was particularly obvious for T11 in the single-color analyses, with reductions being greater for monkey than human cells. Furthermore, in the single-color analyses, the effects of morphine on kinetics of T11 expression were quite similar for both human and monkey cells. In the two color analyses, the simultaneous expression of T11 and Leu3a markers was uniform for both monkey and human cells. The effects of morphine on kinetics of expression of these markers varied only slightly between species. On the other hand, the distribution of Leu2a on T11 cells was markedly different for monkey and human T-cells. Whereas all human Leu2a(+) cells expressed similar numbers of T11 receptors, monkey cells with high-density Leu2a expressed fewer T11 markers than those with low-density Leu2a. The effects of morphine on kinetics of Leu2a and T11 expression were at obvious variance between species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343705 TI - Neuroimmune intercommunication, central opioids, and the immune response to bacterial endotoxin. AB - Muramyl dipeptide is the smallest biologically active fragment of the lipopolysaccharide (LPS) moiety of gram-negative bacteria cell walls. The present report demonstrates that this product, associated with the immune response to bacterial infection, can modify CNS activity. Specifically, it is demonstrated that 6-0-stearoyl-muramyl dipeptide (MDP) can attenuate opiate withdrawal severity in a dose-dependent fashion when injected directly into areas of the brain essential for this phenomenon. In addition, MDP alters both baseline and postnarcotic electrophysiologic responses of four brain areas essential for various opioid activities. Similar findings have been reported for interferon alpha (IFN-alpha), a peptide associated with the immune response to virus. Yet, even though MDP and IFN are shown to exert similar effects on opioid activity, there are also some very distinct differences in the actions of both of these immune response products. These observations suggest that central opioid systems may provide targets for the perception as well as the differentiation of afferent immunologic sensory input to the brain. PMID- 3343707 TI - Dopamine and serotonin inhibition of neurite elongation of different identified neurons. AB - This study demonstrates that a second classical neurotransmitter, dopamine, can act to suppress regenerative neurite outgrowth. Single identified neurons were dissected from two central ganglia of the snail Helisoma, and growth cone motility was studied as neurites regenerated in cell culture. Both dopamine and serotonin inhibited growth cone motility and elongation of neurites. Outgrowth inhibition ranged from sustained arrest to a similar but transient response. The effects of dopamine and serotonin are neuron-selective. Specific neurons affected by dopamine and serotonin represent distinct sets. One neuron was found that responds to both agents. The implications of neurotransmitter regulation of the dynamics of neuronal morphology are discussed. PMID- 3343708 TI - Developmental effect of dimethyl sulfoxide on hypothalamo-neurohypophysial neurons in vitro. AB - Primary dissociated cultures were established from diencephalic tissue of 14-day old fetal rats. Neurons exhibiting immunocytochemical staining for neurophysin appeared in these cultures after 6 days of cultivation. Addition of dimethyl sulfoxide (DMSO) to the culture medium resulted in a slight decrease in total neuronal cell mass as assessed by immunocytochemistry and radio-immunometric quantitation of neuron-specific enolase. In contrast, in DMSO-treated cultures the number of neurophysin-immunoreactive neurons was more than doubled as compared to control cultures. [3H]Thymidine labeling and autoradiography in conjunction with immunocytochemistry for neurophysin showed that this was not due to a mitogenic effect of DMSO on precursor cells. Time-course analysis of the action of DMSO revealed a 6-day time lag between the initiation of treatment and the appearance of increased numbers of neurophysin-immunoreactive cells. These findings suggest that DMSO, which has previously been reported to have a differentiation-inducing effect on malignant transformed cells, may also modulate cellular processes that control differentiation in specific types of neurons in primary culture. PMID- 3343709 TI - Migration of cultured fetal spinal cord astrocytes into adult host cervical cord and medulla following transplantation into thoracic spinal cord. AB - Cell suspensions from 14-day-gestation rat spinal cord, which had previously been soaked for 1 hr in a 2 micrograms/ml solution of Phaseolus vulgaris leucoagglutinin (PHAL), were cultured on collagen gels containing laminin for 2 weeks. Pieces of the gel and attached cells were then transplanted into the dorsal column of adult host thoracic spinal cord. At 1, 2, and 3 months postimplantation (MPI), animals were sacrificed, and the spinal cords were removed, embedded in paraffin, and sectioned at 8 micron for immunohistochemistry at the light microscopic level. Sections were double labeled for PHAL and utilized as a marker for transplant-derived cells and glial fibrillary acidic protein (GFAP), a specific marker for astrocytes. Transplant-derived astrocytes (PHAL-GFAP positive cells) migrated from the transplantation site in both rostral and caudal directions and were observed within the host dorsal column ipsilateral to the transplantation site. At 2 months, lateral migration into the contralateral dorsal column and ipsilateral dorsal horn was observed. At 3 MPI transplant-derived astrocytes were observed in host medulla (nucleus gracilis). Transplant-derived astrocytes were also observed on the glial limitans as far as nucleus gracilis. A migration rate of 0.72 mm/day was calculated, assuming a 14 day delay in the initiation of migration. The ramifications of such extensive migration are discussed with regard to return of function and amelioration of lesion-induced deficits. PMID- 3343710 TI - Some characteristics of muscle-conditioned media with excitatory and inhibitory influences on neurite outgrowth from early neural tube explants. AB - This study examined the growth of basal plate explants from 40-hr chick embryos containing the trigeminal motor nucleus in the presence of target muscle conditioned medium (MCM) from day-4, day-10, and day-18 embryos. We had previously found that MCM derived from the 4-day target tissue enhanced neurite outgrowth from these explants, while target MCM from 10- and 18-day embryos inhibited it. For the present study, target MCM was treated with trypsin to assess the nature of the active fractions, or pre-incubated in polyornithine coated dishes to determine the possible presence and relative contributions of substrate-binding vs. soluble components. Both trypsinization and pre-incubation abolished the outgrowth-enhancing potential of the 4-day MCM, indicating a protein or polypeptide substrate-binding active fraction, with no appreciable active soluble component. When the 10-day and 18-day target MCM were trypsinized, the inhibitory influence was reversed, and neurite outgrowth was enhanced. Similarly, when the MCM from these embryos was pre-incubated over polyornithine, the inhibitory influence was lost and was replaced by a stimulatory one. These results suggest that the 10- and 18-day MCM contain an active inhibitory fraction that is a protein or polypeptide, and which binds to a positively charged substrate. When this inhibitory fraction is inactivated or depleted, an excitatory soluble fraction is revealed. Such a dual nature in MCM has not been seen previously and may be expressed only when the media are assayed with very early neural tissue. PMID- 3343711 TI - Localization of the pool of G4 acetylcholinesterase characterizing fast muscles and its alteration in murine muscular dystrophy. AB - The distributions of acetylcholinesterase and its molecular forms within muscles of normal and dystrophic 129/ReJ mice were established by a concomitant cytochemical and biochemical study performed on 1-mm serial sections of three predominantly fast muscles, i.e., anterior tibialis, extensor digitorum longus, and sternomastoid, as well as the slow-twitch soleus. This comparative study showed the following main findings. 1) In every muscle of both normal and dystrophic mice a) the three asymmetric forms were confined to the motor zone where they systematically codistributed with the endplates, and b) all globular forms, including G4, were concentrated at the motor zone from which they extended over the entire muscle length along a concentration gradient. 2) In the normal muscles, the perijunctional sarcoplasmic cytochemical reaction exhibited by individual fibers was grouped into a well-defined cojunctional acetylcholinesterase compartment in which the endplates were embedded. The overall intensity of the cojunctional cytochemical reaction was either high or low according to whether the muscle was predominantly fast or slow. 3) This cojunctional acetylcholinesterase compartment varied in close parallelism with G4 and thus appeared as the cytochemical correlate of the G4 molecules concentrated around the endplates. In particular, as the shape of the motor zone progressively increased in complexity along with the intricacy of the muscle fiber organization, from sternomastoid to extensor digitorum longus to anterior tibialis, so did both the relative volume occupied by the cojunctional acetylcholinesterase compartment and the proportion of G4. 4) The motor zone of the normal fast-twitch muscles characteristically differed from that of the soleus by the presence of a G4-rich environment around the endplates, which was cooperatively provided by the surrounding fibers. 5) In dystrophic muscles, this cojunctional G4-rich compartment was lost: the cojunctional cytochemical compartment was no longer discernable, while G4 was reduced to a minimal low level similar to that characteristic of the normal soleus. PMID- 3343712 TI - Occurrence of phospholipase A1-A2 and lysophosphatidylcholine acyltransferase activities in axolemma-enriched fractions of brain stem, optic pathway, and cranio-spinal nerves of the rabbit. AB - An axolemma-enriched fraction was isolated and characterized from homogenates of brain stem, pooled optic nerve and tract, and sciatic and hypoglossal nerves of adult rabbits. In these fractions, the phospholipase A1 and A2, as well as the activity of acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine and acyl-CoA:2-acyl-sn glycero-3-phosphorylcholine acetyl transferase, using 1-acyl- and 2-acyl-GPC as acyl acceptors, were studied. The activity of the four enzymes was clearly detectable in the central nervous system (CNS) and peripheral nervous system (PNS) axolemmatic preparations, as well as in other subcellular fractions examined. The axolemma fractions, in which acetylcholinesterase displayed the highest activities, were particularly enriched in the acylation reaction enzymes. These latter showed specific activities about twofold higher compared with those of the homogenates and significant correlation with acetylcholinesterase. The noticeable presence of these enzyme activities in both CNS and PNS axolemma suggests that a deacylation-reacylation system for phospholipids may be operative in this membrane. PMID- 3343713 TI - Classification: the great deception. AB - The linchpin of oncologic statistics might well be thought to be classification based upon the hope that comparisons of natural history and treatment regimes could be compared and controlled worldwide. Many such systems exist for sites within the head and neck; all possess varying degrees of intrinsic error--usually unquantified! A review of three sites by an experienced clinician highlights some of these deficiencies together with their likely significance. The conclusion is reached that although encouraging better recording of clinical and radiologic assessment, cancer statistics based upon existing classification systems can best be compared with a pyramid perched precariously upon its apex! PMID- 3343714 TI - The use of carbon dioxide laser in dealing with fibrous strictures of the larynx and trachea. AB - The carbon dioxide laser has proved valuable in treating patients with severe scarring of the pharynx and supraglottic larynx. There is minimal re-scarring, and an open operation may be avoided. In conjunction with an open procedure, the laser provides a good method of controlling granulation tissue. Two cases of complete pharyngeal stenosis, resulting from caustic ingestion, are described. In one case, repair was achieved by supraglottic laryngectomy and gastro hypopharyngeal transposition which temporarily obscured the larynx completely. The laser was used to re-open the laryngeal airway, following which the patient had normal eating, breathing and speaking. PMID- 3343715 TI - External auditory canal stenosis and atresia: dual flap surgery. AB - Surgical correction of the severely stenosed or atretic external canal still remains a difficult surgical challenge. As more and more techniques are described, it is apparent that the main thrust and emphasis is to prevent late cicatrization or stenosis. The essential principles are to create a wide canal and cover as much raw surface as possible with skin, preferably full-thickness and with an intact blood supply. The following technique, using dual flaps, has been used successfully in 10 consecutive problem ears with unusual underlying pathologies. With follow-up ranging from seven months to four years, there have been no cases of restenosis to date. PMID- 3343716 TI - Evolution of the epidermoid formation and its role in the development of the middle ear and tympanic membrane during the first trimester. AB - In a study of 20 ears from embryos and early fetuses, 16 contained structures recognizable as precursors of the epidermoid formation (EF). The earliest were small, but later they took the form of a long epithelial bud which emanated from the tip of the tubotympanic recess or Eustachian tube. At a later stage still the EF protruded into the lumen of the Eustachian tube. The early formation of the tympanic membrane, the middle ear cavity and the osseous tympanic ring all take place in the vicinity of the EF precursor. It is possible that the EF precursor may act as an organizer, playing a prominent part in the migration of the first pharyngeal pouch towards the first branchial groove and the development of the middle ear and tympanic membrane. PMID- 3343717 TI - Spontaneous temporomandibular joint fistula into the external auditory canal. AB - The clinical and radiological findings in a patient who developed a spontaneous fistula between the right temporo-mandibular joint and the external auditory canal are presented. A high resolution CT scan revealed that the fistula had developed through a congenital dehiscence in the anterior wall of the tympanic bone. PMID- 3343718 TI - Histopathology of chloroform-induced inner ear damage. AB - Inner ear function loss was caused in guinea pigs and rats by injecting chloroform into the middle ear. After symptoms for cochlear and vestibular deficit had been registered, the animals were permitted to survive for one day to five months. Ear histopathology was then studied in celloidin sections. In both species, hair cells and afferent nerve fibers were intact at all survival times. The acute stage of functional loss in guinea pigs was associated with inner ears of normal histological appearance. Within days after chloroform injection a severe otitis media developed which led to fibrous occlusion of the round window and eventually to new bone growth in the middle ear space around the otic capsule. A secondary labyrinthitis was also observed, resulting in endolymphatic hydrops at longer survival times. Different histopathological changes were seen in rats. The tectorial membrane appeared swollen in all cases, the swelling being more severe in more apical turns at longer survival times. It is concluded that only secondary sequela of the initial functional insult can be detected by standard light microscopic histopathology. Chloroform does not cause a chemical labyrinthectomy as previously assumed, although it is severely ototoxic. PMID- 3343720 TI - The cross-sectional osteology of the midface. AB - The midface is a complex anatomical region composed of spaces created by a partitioned bony case. Otolaryngologists must thoroughly understand the organization of this region and be able to relate its structure to both pathological processes and surgical therapy. This study examines serial cross sections of clear polyester-embedded skulls. The midfacial skeleton is resolved into a series of geometric shapes: the pentahedral orbit resting on the tetrahedral maxillary sinus, the wedge-shaped ethmoid pyramid occupying the upper outer quadrant of the v-roofed naso-ethmoid box which is related anteriorly to the folded-disk frontal sinuses and external nasal wedge, and posteriorly to the sphenoid box and triangular pterygopalatine fossa wedge. We show that the weakest region of the fovea ethmoidalis is the lateral wall of the olfactory groove, and we examine the co-planar relationship of the medial maxillary and orbital walls. PMID- 3343719 TI - Invasive squamous cell carcinoma within verrucous carcinoma. AB - A case of invasive squamous cell carcinoma within a verrucous carcinoma is presented in order to illustrate the potential problem of underdiagnosis of these lesions. The epidemiology, natural history and histopathology of verrucous carcinoma, and features which distinguish it from invasive squamous cell carcinoma, are reviewed. Unless rigorous attention is paid to histologic detail, a focus of invasive squamous cell carcinoma may escape detection and radiation induced anaplastic transformation may later be suspected. PMID- 3343721 TI - Otolaryngologic manifestations of amyotrophic lateral sclerosis. AB - Otolaryngological manifestations were examined in a series of 250 patients diagnosed as having ALS between 1976 and 1986. Surgical intervention was only required in 10 cases due to excessive drooling and aspiration. Five patients had submandibular gland excisions with only limited improvement in respect to drooling. One case having a unilateral tympanic neurectomy had significantly better drooling control. Cricopharyngeal myotomy is helpful when dysphagia is predominantly due to cricopharyngeal spasm. In our series, tympanic neurectomy and chorda tympanectomy provide the better control of drooling for these patients and has the added advantage of being performed under local anesthesia. PMID- 3343722 TI - Observations on the efficacy of intranasal beclomethasone dipropionate in cystic fibrosis patients. AB - The authors report the subjective results on the use of intranasal beclomethasone dipropionate in patients with cystic fibrosis. This medication has demonstrated positive results for these patients, whether polyps are present or not, and its use should be considered whenever symptoms of obstruction are present. PMID- 3343724 TI - Digitalized auto-septoplasty. PMID- 3343725 TI - Epidermoid formation in fetal ears. PMID- 3343723 TI - Spontaneous pneumomediastinum and subcutaneous emphysema. AB - Spontaneous pneumomediastinum with subcutaneous emphysema is a well-documented phenomenon which usually follows a benign course and rarely results in circulatory collapse and death. The condition is caused by a sustained increase in the intra-alveolar and intrabronchial pressure with air dissecting along the perivascular spaces of the mediastinum. The majority of patients respond to conservative therapy and rarely require aggressive surgical intervention. Three cases are presented. The anatomy, etiology and the pathophysiology of the disease are reviewed, and the treatment options discussed. PMID- 3343726 TI - Financing residency training in urology. AB - Five educators concerned with changes occurring in the financing of medical education and care reviewed the present status of residency programs and their financing. Future support depends on political decisions as well as demonstrable needs. The effects of anticipated reductions in funding for residents and their programs may be countered by the development of alternative sources and the restructuring of present programs for more efficient operation. The need for leadership is clear. PMID- 3343727 TI - M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium. AB - Of 92 patients who received methotrexate, vinblastine, doxorubicin and cisplatin complete and partial remissions were observed in 69 +/- 10 per cent of 83 adequately treated measurable and evaluable patients with advanced stages (N+M0 and N0M+) transitional cell urothelial cancer. Complete remission was achieved in 37 +/- 10 per cent of the patients clinically, pathologically and after surgical resection of residual disease. With 17 of 31 complete responders (55 per cent) surviving for 26+ to 49+ months, the estimated probability of survival at 2 and 3 years was 71 and 55 per cent, respectively. Partial remission occurred in 31 +/- 10 per cent of the patients, while 8 per cent had a minor response and 23 per cent had progression with median survivals of 11, 11 and 7 months, respectively. Whereas all metastatic sites responded, including the bone and liver, complete tumor regression was observed more frequently with nodal, pulmonary and local regional lesions. Brain metastases occurred within 6 to 42 months in 18 per cent of the responders, half of whom never had systemic relapse. Of the remaining 9 patients 2 with nontransitional cell histological tumors did not respond, 5 (5 per cent) were inadequately treated and 2 were excluded from response data because of inevaluable disease parameters but they were free of disease at 16+ and 31+ months. Toxicity was significant, with 20 per cent of the patients experiencing nadir sepsis, 4 per cent a drug-related death, 31 per cent +1 renal toxicity and 41 per cent +1 mucositis. The applications and advantages of the newly proposed international response criteria for bladder cancer are discussed in reference to 25 patients who underwent surgical re-staging, indicating that the disease was understaged clinically in 24 per cent (T less than P), as well as in reference to attainment of true (pathological) complete remission and to other urothelial tract trials. While this therapy seems to have limited antitumor activity against nontransitional cell histological cancer, stage Tis disease and later development of de novo lesions, the regimen is efficacious in selected patients with advanced urothelial tract transitional cell carcinoma. PMID- 3343728 TI - Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) effect on the primary bladder lesion. AB - Of 50 patients with bladder cancer given 1 to 5 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin in a pilot phase I and II study 63 per cent of 41 with pure transitional cell stage T2-4 lesions responded. While significant downstaging occurred by transurethral resection of the bladder in 70 per cent and by cytology in 60 per cent of the patients, the final T response rate by all noninvasive clinical staging procedures, including sonography and computerized tomography, revealed complete remission in 24 per cent and partial remission in 39 per cent. Of 30 patients who underwent pathological staging 33 per cent achieved stage P0 and 17 per cent stage Tis disease or P less than T. Despite extensive re-evaluation by transurethral resection of the bladder and other noninvasive staging procedures, a clinical staging error (T versus P) of 38 per cent was observed. Of the other 9 patients 4 with mixed nontransitional cell histological findings at presentation never achieved complete remission, although 3 had resolution of all transitional cell elements and 5 (10 per cent) were inevaluable. The toxicity of the regimen was generally acceptable but 6 per cent of the patients required hospitalization for neutropenic fever. While this active regimen can clinically (T) and pathologically (P) induce downstaging in a significant number of patients with primary bladder tumors, this pilot study has raised serious questions concerning the design of future nonrandomized and randomized neoadjuvant studies. PMID- 3343729 TI - Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for extravesical urinary tract tumors. AB - A total of 11 patients with stage T2-4N0M0 extravesical tumors (prostate, prostatic urethra, urethra and ureter) received 1 to 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin. Of 10 evaluable patients 4 (40 per cent) had downstaging to T0 disease with a clinical complete remission observed in 3 of 5 (60 per cent) with transitional cell tumors of the prostate and prostatic urethra. Four patients with urethral tumors of mixed or nontransitional histology failed to achieve a complete remission. The disease was staged pathologically in 4 patients: 1 had a partial remission and 3 had progression (all 4 had residual disease). Because therapy with methotrexate, vinblastine, doxorubicin and cisplatin induced only significant tumor regression of transitional cell elements of extravesical tumors and because it was ineffective against mixed histological tumors and in preventing new stage Tis lesions, surgical resection of such lesions is required. PMID- 3343731 TI - Extracorporeal shock wave lithotripsy and its effect on renal function. AB - Extracorporeal shock wave lithotripsy has become a major treatment modality for symptomatic upper tract renal stone disease. Although proved to be effective in disintegrating stones the short-term and long-term effects on renal function are not yet known. We evaluated several basic physiological parameters, namely creatinine clearance, fractional sodium excretion, protein excretion and urine osmolality before and after extracorporeal shock wave lithotripsy in 26 consecutive patients in an attempt to quantitate changes in renal function. In addition, a 3 to 6-month followup study of patients showing excessive protein excretion with extracorporeal shock wave lithotripsy also is reported. Our data suggest that with extracorporeal shock wave lithotripsy transient nephrotic range proteinuria occurs immediately after treatment, returning to normal values within 3 to 6 months after treatment without a change in the glomerular filtration rate. The glomerular filtration rate increases after successful extracorporeal shock wave lithotripsy in patients with kidneys obstructed by the treated stone before the start of the procedure, and the kidney appears to maintain its ability to dilute urine and to conserve sodium after treatment. PMID- 3343730 TI - Familial aggregation of renal calcium stone disease. AB - The question of a familial predisposition towards stone formation in primary nephrolithiasis has not been explored completely. In a sample of 214 calcium stone patients, and 428 age and sex-matched controls we observed a higher frequency of stones among the first degree relatives of stone patients compared to the relatives of controls. A family history of renal stones was more common among the female (45 per cent) than among the male patients (31 per cent). There was no relationship between family history of renal stones, and abnormal calcium and oxalate excretion rates. A significant association between a family history and a higher urinary pH was observed among the female calcium stone patients. A genetic defect in urinary acidification with variable expressivity might be associated with a high frequency of stone formation. Moreover, uric acid excretion was higher in male stone patients with a family history of stones. Finally, the parents and siblings of the renal stone patients were affected more by calculi than were the corresponding relatives of their spouses. PMID- 3343733 TI - Ureteroscopy. AB - From early 1982 to December 1985, 317 patients underwent 346 transurethral ureteroscopic procedures at our institution. For most patients the intramural ureter was dilated with balloon dilators and all procedures were performed under fluoroscopic control. The over-all success rate for lower ureteral stone removal was 95 per cent, which increased to 97 per cent for stones treated in 1984 and 1985. Ureteroscopy is useful for the evaluation of idiopathic gross hematuria, and for the diagnosis and treatment of ureteral and renal pelvic tumors. The over all mean hospital stay was 4.9 days and the procedure has been a significant addition to our armamentarium. PMID- 3343732 TI - Clinical efficacy of high frequency jet ventilation during extracorporeal shock wave lithotripsy of renal and ureteral calculi: a comparison with conventional mechanical ventilation. AB - The use of high frequency jet ventilation compared to conventional mechanical ventilation during general anesthesia for extracorporeal shock wave lithotripsy of renal or ureteral calculi can reduce stone movement. This decrease in stone movement theoretically lessens the total shock and energy requirements for stone fragmentation and perirenal tissue damage. To assess these theoretical advantages of high frequency jet ventilation, we studied patients undergoing extracorporeal shock wave lithotripsy to determine differences in stone movement during high frequency jet and conventional mechanical ventilation (30 patients), and in total shock requirements (1,174 patients). Mean stone movement in the 30 patients was 34.3 +/- 4.3 mm. during conventional mechanical ventilation compared to 4.1 +/- 1.9 mm. during high frequency jet ventilation (p less than 0.001). Mean total shocks were 1,542 +/- 212 (452 patients) during conventional mechanical ventilation compared to 1,217 +/- 165 (722 patients) during high frequency jet ventilation (p less than 0.001). Only 1 patient in the study had clinically significant perirenal tissue damage. We conclude that high frequency jet ventilation when compared to conventional mechanical ventilation results in clinically and economically beneficial decreases in total shocks for extracorporeal shock wave lithotripsy fragmentation of renal or ureteral calculi. PMID- 3343734 TI - Extracorporeal shock wave lithotripsy for ureteral stones: a retrospective analysis of 417 cases. AB - We treated 417 patients with upper ureteral stones with extracorporeal shock wave lithotripsy. All patients with obstructing stones underwent retrograde manipulation, which was successful in 57 per cent. Management of obstructing stones in situ (215 patients) with and without decompression of the collecting system required additional treatments in 13 per cent and ancillary procedures in 25 per cent. Nonocclusive ureteral stones were not manipulated. Treatment of these stones in situ slightly increased the need for postoperative ancillary procedures, compared to successful repositioning into the kidney (5.9 versus 3 per cent). Secondary treatments, however, were necessary as often as with occlusive stones. The main reason for failure of extracorporeal shock wave lithotripsy was the lack of fluid around an impacted stone. An energy absorptive effect of muscle tissue for stones projecting on the psoas muscle could not be demonstrated. The best and most consistent results were obtained when the stone was manipulated successfully into the renal collecting system. PMID- 3343735 TI - Hammock anastomosis: a nonrefluxing ureteroileal anastomosis. AB - During a 9-year period diversion was performed in 48 patients by an antireflux ureteroileal anastomosis. Followup was possible in 30 patients (57 renal units). Among these 57 ureteroileal anastomoses only 3 cases of stenosis (6 per cent) and 11 cases of reflux (less than 20 per cent) were observed. These results are roughly comparable to those with colon conduits. The 30 patients included 2 in whom the antireflux anastomosis formed part of a continent ileal stoma. The method is described and the results are discussed. PMID- 3343736 TI - Selection of intestinal segments for bladder substitution: physical and physiological characteristics. AB - Detubularized bowel segments provide greater capacity at lower pressure and require a shorter length of intestine than do intact segments. Four factors account for their superiority: 1) their configuration takes advantage of the geometric fact that volume increases by the square of the radius so that a patch or pouch has a larger diameter than a tube, 2) they accommodate to filling more readily because, as LaPlace's law states, the container with the greater radius and, thus, the greater mural tension will hold larger volumes at lower pressure, 3) compliance is superior to that of the tubular bowel and 4) contractile ability is blunted by the failure of contractions to encompass the entire circumference. For these reasons detubularized segments store more urine at lower pressures. PMID- 3343737 TI - Surgical treatment of the incontinent female patient with myelomeningocele. AB - Surgical therapy was required for 42 incontinent female patients with myelomeningocele who had urodynamically documented high pressure bladders. Conservative treatment consisting of cholinolytic and alpha-adrenergic agents, and intermittent self-catheterization had failed. The surgical approach consisted of perivesical denervation (for hyperreflexia), Burch bladder neck suspension, enlargement cystoplasty and ureteral reimplantation when required. Among 33 patients (79 per cent) there was no incontinence on intermittent self catheterization and 6 (14 per cent) had improvement with rare urgency or stress incontinence. In 3 patients (7 per cent) sphincteric incompetence required a transvaginal sling procedure. PMID- 3343739 TI - Age changes in the human female urethra: a morphometric study. AB - Aging in the human female urethra can contribute towards urinary problems. To our knowledge the effect of age on urethral tissues has not been quantified previously. Histological sections were prepared from 8 regions along the length of the urethra from 26 women between 19 and 88 years old. Using quantitative morphological techniques the relative volume fractions of various tissue components were determined. As age increased there was a decrease in the relative volume of striated muscle and blood vessels, and an increase in the relative volume of connective tissue. There was no change in the smooth muscle components. These age changes in the human female urethra may lead to impairment of urethral function. PMID- 3343738 TI - Fascial sling to correct male neurogenic sphincter incompetence: the McGuire/Raz approach. AB - We report the surgical approach used in 4 male myelomeningocele patients suffering from severe urinary incontinence owing to poor bladder compliance and sphincter incompetence. While bladder compliance was corrected by enlargement cystoplasty the sphincteric incompetence was treated by an autologous fascial sling around the bladder neck with excellent results. We consider this operation as an alternative to the artificial urinary sphincter in cases of male neurogenic sphincter incontinence. PMID- 3343740 TI - Penile sufficiency: an operational definition. AB - In an effort to obtain a more precise definition of erectile sufficiency for vaginal penetration 19 normal men were exposed to an erotic videotape and recordings of penile tumescence were obtained. The subjects were instructed to signal with a push button switch when they had attained an erection they judged sufficient for penetration. They were asked to signal a second time when a full erection had been reached. The results showed that in all but 1 case maximal tumescence was recorded polygraphically before the subjects signaled sufficiency. In addition, there was a considerable interval between the perception of sufficiency and the perception of a full erection during which, nevertheless, no further changes could be detected by strain gauge measurement. These data suggest that standard assessment techniques are not sensitive to penile changes in the upper ranges of tumescence. Of interest to the developing area of diurnal penile tumescence for the etiological diagnosis of impotence was the observation that a significant percentage (37 per cent) of normal subjects were unable to achieve a full erection during visual sexual stimulation under laboratory conditions. PMID- 3343741 TI - Sympathetic skin response: a new test to diagnose ejaculatory dysfunction. AB - Sympathetic skin responses were elicited from the palm and sole (plantar) with electrical stimulation on the dorsal nerve of the penis in 24 individuals. The palmar and plantar sympathetic skin responses were obtained in 12 subjects with normal ejaculatory function. On the other hand, the plantar sympathetic skin response was absent in 11 of 12 patients who lacked ejaculation. Since the plantar sympathetic skin response is correlated closely to the mechanism of ejaculation, this test is expected to be helpful to diagnose sexual dysfunction and to monitor the effects of treatment. PMID- 3343742 TI - A new surgical approach for the correction of female stress urinary incontinence. AB - A new surgical approach for the correction of female urinary stress incontinence has been devised. The retropubic space is entered through a dome-shaped incision in front of the urethral meatus in the anterior vaginal vestibule. The incision does not extend beyond the lower edge of the symphysis pubis. With the tip of the hemostat or scissors the incision is opened longitudinally, and the lower legs of the incision are opened and freed up from the bulbocavernosus muscles. The bleeders are controlled. The layers of the genitourinary diaphragm are opened beginning from behind the symphysis pubis and the retropubic cavity is exposed. Then, the vesical neck and urethra are sutured to the back of the symphysis pubis in the midline. With this procedure there is no abdominal incision. The vesical neck and urethra are well exposed. The back of the symphysis pubis can be visualized with the patient in an exaggerated Trendelenburg position. All except 1 patient were cured. Hospitalization and postoperative recovery times were markedly reduced. The procedure affords easy access for drainage of the retropubic space. A new avenue is provided for insertion of an artificial sphincter to achieve urinary continence and for vesical neck colposuspension. PMID- 3343743 TI - Surgical repair of varicocele at puberty: preventive treatment for fertility improvement. AB - In 40 pubertal boys with a varicocele a comparative followup study was performed to evaluate the efficacy of surgical correction of the varicocele in this age group in regard to improvement of fertility after completion of sexual maturation. The varicocele was corrected surgically in 24 patients and it was left uncorrected in 16. Testicular atrophy was noted in all cases at the initial visit and after followup. Of the 24 corrected patients 16 had atrophy of at least 1 testis before surgical treatment, whereas only 7 demonstrated atrophy after followup. Of the 16 uncorrected patients testicular atrophy was noted in 8 at the initial visit but 12 had atrophy after followup. Semen examination of 23 patients who had completed sexual maturation demonstrated a higher quality of routine seminal parameters, for example sperm density, sperm motility and percentage of morphologically normal spermatozoa, in the corrected group than in the uncorrected group. PMID- 3343744 TI - An experimental study of methods to produce intrascrotal testicular fixation. AB - Methods to produce fixation between the tunica albuginea (visceral tunica vaginalis) and surrounding structures were used in Sprague-Dawley rats as an experimental model of orchiopexy to prevent testicular torsion. Eversion of the parietal tunica vaginalis without suture, or with absorbable or nonabsorbable suture produced excellent scarification, as did the use of talc. Absorbable and nonabsorbable suture, when placed between the parietal tunica vaginalis and tunica albuginea (visceral tunica vaginalis), produced only minor degrees of inflammation. Tetracycline instillation similarly failed to produce a significant inflammatory response. PMID- 3343745 TI - M-VAC chemotherapy in the management of locally advanced bladder cancer. PMID- 3343746 TI - Further evidence that renal oncocytoma has malignant potential. AB - We report a case of bilateral renal oncocytoma. The right tumor infiltrated the renal capsule focally, and the left tumor penetrated through the capsule into the surrounding perinephric fat and extended into the left renal vein. Karyotyping of the left oncocytoma showed loss of chromosomes 1 and Y (-1,-Y). These karyotypic anomalies, along with the capsular, perinephric fat and renal vein involvement, indicate that renal oncocytomas, despite similar gross and microscopic pathological characteristics, are a heterogeneous group of tumors, some of which have malignant (local invasiveness) potential. PMID- 3343748 TI - Benign villous polyp with prostatic type epithelium of the penile urethra. AB - We report a case of a benign polyp of the penile urethra composed of prostatic type epithelial tissue. The etiology, pathology, diagnosis and treatment of these uncommon lesions are discussed. PMID- 3343747 TI - Nephroureterectomy after radical cystectomy. AB - We report 6 cases of upper tract transitional cell carcinoma that developed after total cystectomy with ileal loop diversion. We conclude that if nephroureterectomy is to be used as treatment, excision of the ureteroileal anastomoses should be done. PMID- 3343749 TI - Retrograde ejaculation owing to ectopic erectile tissue. AB - We report a case of retrograde ejaculation caused by ectopic erectile tissue in the posterior urethra. Transurethral resection of the tissue resulted in antegrade ejaculation. PMID- 3343750 TI - Replantation of the testis: report of a case. AB - To our knowledge there has been no report to date of successful testis replantation after complete traumatic severance of the funiculus within the scrotum. We report a case in which both funiculi were cut completely (one of which was severed 0.8 cm. proximal to the upper pole of the testis, and the other just at the junction of the funiculus and the testis). We successfully rejoined the testis with the funicular stump to the proximal cut end of the right side using a microsurgical technique. The total ischemia period of the replanted testis was 6 hours. The penis was erect 4 days postoperatively and blood testosterone level was within the normal range. At testicular biopsy 120 days postoperatively the germ cells could be seen in various stages of development and the appearance of the Leydig cells was normal. PMID- 3343751 TI - The use of 99mtechnetium in the diagnosis of patent processus vaginalis. AB - We report 2 cases of scrotal swelling after placement of peritoneal catheters. 99mTechnetium intraperitoneal scanning was used to identify a patent processus vaginalis in each case. This simple, rapid, and nontoxic method can be used routinely to screen patients for a subclinical hernia before institution of intraperitoneal therapy. PMID- 3343752 TI - The organic matrix of urinary uric acid crystals. AB - We have demonstrated that urinary uric acid crystals contain an organic matrix within the crystalline boundaries, morphologically similar to that of uric acid stones. Among several glycosaminoglycans in urine, heparan sulfate was almost exclusively identified in this matrix, as in that of uric acid stones. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that several proteins in urine were incorporated in this matrix on a selective basis; two of which were albumin and Tamm-Horsfall mucoprotein. An affinity of uric acid or urate for selective urinary macromolecules in a liquid phase was supposed to be the origin of this matrix. But the proteins in the uric acid stone matrix were not separated by SDS-PAGE. Therefore we could not conclude whether the organic matrix of urinary uric acid crystals is similar to that of uric acid stones. PMID- 3343753 TI - Vascular integrity of the distal ureter following combined tapering and cross trigonal reimplantation. AB - Massive unilateral hydroureteronephrosis was created in 20 female dogs by ligating the urographically normal prevesical ureter. Over a 14-day period the obstructed ureter dilated to an average of 15.3 mm. A ureteral tapering procedure was performed by lateral darting and posterior folding of the resultant flap, followed by a cross-trigonal reimplantation. One anastomotic stricture resulted; in the remaining 19 animals, ureteral peristalsis was restored, the ureteral diameter was reduced 61.9 per cent and hydronephrosis was resolved. Histological studies on the tapered segments of these 19 animals showed that the subadventitial blood supply was preserved with fibrotic occlusion of the folded flaps. These results demonstrate that no significant vascular compromise after ureteral tapering and cross-trigonal reimplantation occurs. Success rates comparable to those of conventional ureteral tailoring can be achieved by this technically simplified form of reconstructive surgery. PMID- 3343754 TI - Effect of age on in vivo urinary bladder function in the rat. AB - The effects of age on micturition in male Fischer 344 rats, ages five to seven, 16 to 18 and 22 to 24 months, were studied. The 24 hr. water intake, 24 hr. urine output, frequency and volume of each micturition were obtained from rats housed individually in metabolic cages. Intravesical pressure and volume at which the micturition contraction occurred were evaluated using natural-fill cystometry. The 24 hr. water intake and urine output increased significantly with advancing age; 22 to 24 months rats showed a 39% increase in water intake and a 93% increase in urine output compared to five to seven month rats. The increase in urine output observed in the 22 to 24 month old rats was manifested by a 95% increase in volume per micturition and a 52% increase in frequency of micturition compared to five to seven month old rats. The pressure at micturition (PAM) was 100% greater in 22 to 24 and 16 to 18 month old rats compared to five to seven month old rats with no age-related difference in bladder volume at micturition (BVM). These studies demonstrate that in vivo micturition changes with age in the male F344 rat. Although there were no overt urological dysfunctions observed in the aging rats, the alterations in function would indicate that there were changes in either the mechanisms controlling micturition, or changes in the musculature itself. These possibilities will be the subject of further investigations. PMID- 3343755 TI - Metabolic acidosis after bladder replacement: comparison of severity and reversibility in ileal and colonic reservoirs. AB - Metabolic acidosis developed frequently after ureterosigmoidostomy and rectosigmoid bladder construction but has been reported rarely after the newer methods of continent urinary diversion which also employ intestinal reservoirs. We created an animal model in which to compare the metabolic effects of bladder replacement with segments of ileum or colon and the potential for reversing these derangements with nicotinic acid and chlorpromazine. One year after six dogs' bladders were replaced by colon (three) or ileum (three), all dogs appeared in excellent health and were free of urinary tract obstruction and clinical infection. Both groups of dogs were severely acidotic with diminished arterial pH and arterial and venous total CO2 concentrations although normal serum electrolytes and creatinine concentrations were maintained. Both groups of dogs absorbed approximately one half the urinary sodium, chloride and urea presented to their intestinal reservoirs. After treatment with nicotinic acid and chlorpromazine, the metabolic status of both groups of animals improved. Although nicotinic acid reduced urinary excretion of electrolytes more effectively than chlorpromazine, nicotinic acid was not more effective for reversing metabolic acidosis. When nicotinic acid was provided as an adjunct to sodium bicarbonate therapy in two animals acidosis was corrected at reduced doses of sodium bicarbonate. Based upon this work in an animal model, there does not appear to be a metabolic advantage to intestinal reservoirs which incorporate ileum versus colon. However, asymptomatic patients with normal serum electrolytes and creatinine concentrations may be acidotic. The effects of long term mild acidosis are unknown. However, if therapy is required to prevent diminution of whole body buffers or changes in bone density specific therapy with nicotinic acid or chlorpromazine may reduce the requirement for alkali for correction of metabolic acidosis. PMID- 3343756 TI - Treatment of experimental bladder cancer with hyperthermia and phase transition liposomes containing methotrexate. AB - Serially transplanted murine bladder cancer was treated with localized capacitive radiofrequency hyperthermia and liposome-delivered methotrexate (MTX). Liposomes were manufactured to retain MTX at 37C but specifically release encapsulated MTX as they passed through preheated tumors. When compared to controls, neither free MTX nor liposome-delivered MTX caused significant tumoricidal activity. Heat alone did cause a slowing of tumor growth and an increase in animal survival. Because large unilamellar liposomes are known to be cleared by the liver, sixteen animals were autopsied to determine the extent of liver toxicity which may have been a result of the various treatments. No hepatotoxic effects were observed after injection of liposomes containing MTX or other experimental combinations of drug and/or liposomes. PMID- 3343757 TI - Interactions between bladder tumor cells as tumor spheroids from the cell line J82 and human endothelial cells in vitro. AB - Multicellular tumor spheroids (MCTS) are a reliable model of nonvascularized tumor cell aggregates showing a well defined three-dimensional growth pattern and are comparable with small metastatic cancer cell complexes in blood circulation. In the present study we have established a co-culture system of multicellular bladder tumor spheroids with human endothelial cells on extracellular matrix (ECM) in order to investigate morphological and proliferative changes of endothelial and tumor cells within a defined time of cell-cell interaction. The MCTS--endothelial cell--extracellular matrix complex was observed within coculture periods from 1/2 to seven days. Morphological changes (light microscopy, scanning and electron microscopy) indicated that MCTS are not influenced by cocultured endothelial cells. The tumor cells invaded into the ECM after degradation of endothelial cells in the center of the contact zone. Endothelial cells, however, showed degenerative changes as well as a complex reaction in their proliferation activities. We could recognize an initial increase of proliferation of endothelial cells next to the MCTS. Later on, endothelial cells next to invading tumor cells showed changes in morphological polarity. The model system used has the advantage of using human tumor tissue. It distinguishes between basic cellular mechanisms like adherence, migration, DNA synthesis and proliferation in the study of the contact of tumor cells and vascular endothelial cells as an important event in hematogenous tumor spread. PMID- 3343759 TI - Investigative grammar. PMID- 3343758 TI - Bone resorption induced by transplanted bladder tumor (MBT-2) in mice. AB - The high incidence of metastatic bone resorption in urological cancer makes it necessary for clinicians to look for a valid experimental model to investigate basic interaction between cancer cells and bone in order to improve the treatment. A new model of bone resorption has been defined, namely the subcutaneous injection of tumor cell suspensions of invasive transitional cell carcinoma of the bladder (MBT-2) into mice after the periosteum of the calvaria has been disrupted. The tumor induced osteolysis associated with osteoclast proliferation with reactive bone formation. Moreover, we were able to show hypercalcemia accompanied with local bone resorption in this model. PMID- 3343761 TI - What should polio immunization policy be? Public Health Service expects advice soon. PMID- 3343760 TI - Treatment INDs: promising, problematic. PMID- 3343762 TI - Cyclosporine, in combination with other drugs, studied in insulin-dependent diabetes therapy. PMID- 3343763 TI - Boxing: AIDS? PMID- 3343764 TI - Insulin-dependent diabetes mellitus called 'epidemiologist's dream'. PMID- 3343765 TI - Leads from the MMWR. Case of paralytic illness associated with enterovirus 71 infection. PMID- 3343766 TI - Leads from the MMWR. Arthritis program--Missouri. PMID- 3343767 TI - Long hours and risks to and from residents. PMID- 3343768 TI - The effect of metoclopramide treatment on diabetic cystoparesis. PMID- 3343769 TI - Physician referrals in a competitive environment. PMID- 3343770 TI - Aspirin-induced esophageal hemorrhage. PMID- 3343771 TI - Cerebral vasculitis associated with cocaine abuse or subarachnoid hemorrhage? PMID- 3343772 TI - Dioxins and dibenzofurans in blood and adipose tissue of Agent Orange-exposed Vietnam veterans and matched controls. AB - Vietnam veterans who were heavily exposed to Agent Orange exceeded matched control subjects in both blood and adipose tissue levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) but not in the levels of the 12 other 2,3,7,8 substituted dioxins and dibenzofurans that were detected. Since only TCDD among these compounds was present in Agent Orange but all are present in the population of the industrialized world, it is likely that the elevated TCDD levels arose from wartime exposure. The high correlation (r = +.89) of blood with adipose tissue level suggests that there may be a mobile equilibrium between them and that blood measurement could replace adipose tissue measurement of TCDD levels, making the collection of human data less invasive. PMID- 3343773 TI - Birth defects in the Seveso area after TCDD contamination. AB - A study on the frequency of birth defects was conducted in the area around Seveso, Italy, which was contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin in July 1976; this has been the largest population ever exposed to dioxin. From Jan 1, 1977, to Dec 31, 1982, a total of 15,291 births (still and live) were examined, and malformations were reported to an ad hoc birth defects registry. In the most highly contaminated area, 26 births were observed. None of these infants had any major structural defect. Two infants had mild defects. The frequencies of major defects detected in the areas of low or very low contamination were 29.9/1000 and 22.1/1000, respectively. A frequency of 27.7/1000 was registered in the control area. Relative risks were calculated for specific categories of birth defects and for grouped malformations. Although the data collected failed to demonstrate any increased risk of birth defects associated with 2,3,7,8 tetrachlorodibenzo-p-dioxin, the number of exposed pregnancies was not big enough to show a low and specific teratogenic risk increase. PMID- 3343774 TI - Return to work after a first myocardial infarction. A test of multiple hypotheses. AB - The relationship between return to work within one year after a first myocardial infarction and selected sociodemographic, health, psychosocial, and vocational characteristics was assessed in 151 patients aged 24 to 70 years. Seventy-two percent of the sample returned to work. Education, physical activity associated with employment, severity of myocardial infarction, perception of health status, financial incentives, socioeconomic status, treatment hospital, rated social health status, locus of control, satisfaction with work, and early entry into the job force each proved to be significantly associated with return to work in independent univariate analyses. A stepwise multivariate regression analysis identified only the first four factors as important predictors of return to work. Further analyses show that given knowledge of the patients' educational level and the physical activity associated with employment, 71% of patients who returned to work were correctly classified. Return to work proved easier to predict than work disability. More knowledge is needed about the factors that are critical to a failure to resume employment after a myocardial infarction. PMID- 3343775 TI - Future plans for cancer control. PMID- 3343776 TI - Interhospital transfer of acutely ill cardiac patients. PMID- 3343777 TI - A piece of my mind. Dear John. PMID- 3343778 TI - Will exercise help keep women away from oncologists--or obstetricians? PMID- 3343779 TI - Diabetes in Mexican-Americans: pressing problem in a growing population. PMID- 3343780 TI - Radon risk assessed. PMID- 3343781 TI - Leads from the MMWR. Henoch-Schonlein purpura--Connecticut. PMID- 3343782 TI - The labeling of specimens as infectious. PMID- 3343783 TI - Use of urinary cotinine to estimate exposure to tobacco smoke. PMID- 3343784 TI - Gender offender! Will the epicene yet save JAMA? PMID- 3343785 TI - Hypochondriasis and somatization. PMID- 3343786 TI - Giardia in the well. PMID- 3343787 TI - Tall tubercular lungs. PMID- 3343788 TI - What were those crystals? The dissolution and disintegration of insulin. PMID- 3343789 TI - Human immunodeficiency virus antibody testing. A description of practices and policies at US infectious disease-teaching hospitals and Minnesota hospitals. AB - A questionnaire that asked about policies concerning the use of human immunodeficiency virus (HIV) antibody tests was sent in January 1987 to the 200 hospitals in the United States that conduct infectious disease (ID) fellowship training (US ID hospitals) and to all 171 short-term-care Minnesota hospitals. Information was received from 189 of the US ID hospitals (94.5%) and from 160 (94%) of the Minnesota hospitals. Only 49% of the US ID hospitals and 37% of the Minnesota hospitals had an HIV antibody test-ordering policy; 47% of the US ID hospitals and 39% of the Minnesota hospitals had a specific educational program for physicians about the HIV antibody test; and 62% of the US ID hospitals and 41% of the Minnesota hospitals had an HIV autopsy policy. Marked variety existed in approaches to handling test results, obtaining patient consent, and providing risk-reduction information among the hospitals surveyed. These data suggest the need for a consensus on optimal use of HIV antibody testing at hospitals. PMID- 3343791 TI - Breast cancer in relation to early use of oral contraceptives. No evidence of a latent effect. AB - A long-term effect of oral contraceptives (OCs) on breast cancer risk has been suggested as an explanation for some studies' failure to detect an association between OCs and breast cancer. To address this latency hypothesis, we analyzed data on 4714 case subjects and 4540 control subjects from the population-based Cancer and Steroid Hormone Study. No support was evident for a latent effect of OCs on breast cancer risk through age 54 years: among parous women who had cumulated more than six years of OC use before their first term pregnancy, the risk of breast cancer, relative to nonusers before first term pregnancy, was 0.6 at zero to four years after first term pregnancy (95% confidence interval [Cl], 0.2 to 1.8), 0.7 at five to nine years (95% Cl, 0.3 to 1.7), and 1.1 at ten to 14 years (95% Cl, 0.3 to 3.9). Among nulliparous women with more than six years of OC use in total, the relative risk of breast cancer, by interval from last use of OCs, was 1.3 at zero to four years (95% Cl, 0.8 to 2.0), 1.1 at five to nine years (95% Cl, 0.5 to 2.0), and 0.6 at ten to 14 years (95% Cl, 0.1 to 3.7). PMID- 3343790 TI - Risk factors for ectopic pregnancy. A population-based study. AB - To evaluate the association between ectopic pregnancy and 22 potential risk factors, we conducted a population-based case-control study. The investigation included 274 cases diagnosed from 1935 through 1982 in residents of Rochester, Minn, and 548 matched controls selected from live-birth deliveries. Risk factor information documented prior to the last index menstrual period was obtained via medical record abstract. Univariate matched analyses revealed nine variables associated with a significantly elevated relative risk of ectopic pregnancy. Following conditional logistic regression, four variables remained as strong and independent risk factors for ectopic pregnancy: current intrauterine device use (relative risk, 13.7; 95% confidence interval, 1.6 to 120.6), a history of infertility (relative risk, 2.6; 95% confidence interval, 1.6 to 4.2), a history of pelvic inflammatory disease (relative risk, 3.3; 95% confidence interval, 1.6 to 6.6), and prior tubal surgery (relative risk, 4.5; 95% confidence interval, 1.5 to 13.9). Theoretically, any condition that prevents or retards migration of the fertilized ovum to the uterus could predispose a woman to ectopic gestation. Further research is needed to clarify the impact of other potential risk factors in the etiology of ectopic pregnancy. PMID- 3343792 TI - Hospital policies on HIV antibody testing. PMID- 3343793 TI - Ectopic pregnancy and reproductive technology. PMID- 3343794 TI - A piece of my mind. The trapeze. PMID- 3343795 TI - Research activities and interests of dietitians. AB - A survey was conducted to ascertain research involvement and interests of dietitians. The survey questionnaire was developed and mailed to 1200 dietitian members of The American Society of Parenteral and Enteral Nutrition (A.S.P.E.N.). Usable responses numbered 424 (35.3%); 84% were A.S.P.E.N. members 5 years or less. Currently 46% and previously 17% of respondents served on nutrition support (NS) teams. Two-thirds of the group either completed or were enrolled in a graduate program. Only one-half of the respondents had statistics and/or research methodology courses. Half the group spent no time in research, 10% gave 10-50 hr/week and nearly 80% wanted to spend more time in this activity. One-fifth were principal investigators (PI), 27% were co-investigators and 29% had collected data for others. Although 16% wrote proposals, fewer than 10% had projects approved and/or funded; co-investigators were more successful than PIs in this regard. Several (22.2%) presented research papers or posters and 36% gave seminars, case studies, or short presentations. One-fifth (20.8%) published research articles and 20.3% published other works. More than 80% expressed interest in collaborative research, perhaps because many felt they lacked skills needed to develop research designs, write proposals, analyze data, obtain funding, and get published. Most said research was not rewarded, of a low priority, and generally ignored by the dietetics department; 60.5% had great interest in research and 37.1% had adequate research opportunities. No significant differences were observed for those with graduate degrees or for members of NS teams but A.S.P.E.N. dietitians appeared to be more active in research than other dietitians. PMID- 3343796 TI - Calculation of metabolic expenditure and substrate utilization from gas exchange measurements. AB - At least nine different equations have been published for calculating metabolic expenditure by indirect calorimetry. This study examined the differences between equations when they are used for the nutritional assessment in an intensive care unit (ICU). Oxygen consumption and carbon dioxide production were measured in 36 ICU patients and used to calculate metabolic expenditure with the nine equations. The equations produced differences in metabolic expenditure which averaged from 0.8-96 kcal/day. The largest difference produced by any two of the nine equations was 189 kcal/day. Although differences in original stoichiometric data have resulted in numerous different equations for the calculation of metabolic expenditure, these differences are not clinically important. It makes little difference which equation is used for nutritional assessment in an ICU. PMID- 3343797 TI - Effects of L-carnitine infusion on intralipid clearance and utilization. Study carried out in septic patients of an intensive care unit. AB - Endogenous and exogenous supplies of carnitine are decreased in septic patients under total parenteral nutrition, while carnitine urinary elimination is increased. But the increase of lipid role in the energetic cover requires a greater intervening role of tissue carnitine. So one may hope that in septic patients additional supply of L-carnitine would increase the catabolism of infused lipids. Twenty-eight septic patients, admitted in an intensive care unit were given parenteral nutrition (200 g of glucose, 12.5 g of N/24 hr). On the day of the study, 250 ml of Intralipid 20% (Kabi Vitrum) were administered in 4 hr. During the same period 13 patients were infused with 2 g of L-carnitine (Sigma Tau). The remaining 15 patients constituted the control group. Basic plasma levels of triglycerides, nonesterified fatty acids, free glycerol, phospholipids, and ketone bodies remained within physiological limits. They increased during the lipid infusion and returned to initial values, 4 hr after the end of the infusion. Free and total carnitine levels and free/total carnitine ratio were comparable to healthy subjects' reference values. These parameters increased during L-carnitine infusion. This infusion had no effect on exogenous lipid clearance. However, it seemed to increase the uptake and the hepatic oxidation of circulating fatty acids. It invalidated the increase of lactate and pyruvate that had been noticed when lipids were solely infused. PMID- 3343798 TI - Dealing with medical malpractice. PMID- 3343799 TI - Birth defect suits: their avoidance. PMID- 3343800 TI - CAPD: a primer for the family physician. PMID- 3343801 TI - New developments and therapeutic applications in gastrointestinal endoscopy. PMID- 3343802 TI - Primary extraovarian dysgerminoma. PMID- 3343803 TI - Heartland HMO. PMID- 3343804 TI - [Value of 2-D echocardiography in the detection of stress-induced wall-motion abnormalities in coronary heart disease--a comparison with biplane cineventriculography]. AB - To determine the accuracy of echocardiography in assessment of exercise-induced wall motion abnormalities, the results of stress-echocardiography were compared with exercise-cineventriculography. In 56 consecutive patients biplane cineventriculography at rest and immediately after supine bicycle exercise was performed. Cross-sectional echocardiography was obtained using the apical 2- and 4-chamber view for LV imaging under identical exercise conditions. In 6 of the 56 patients 2-D echo, in 8 patients LV-angio, and in 2 patients both methods were of inadequate quality during exercise. Thus, in 40 patients (34 patients had coronary artery disease) local wall motion of 360 wall segments was analysed. 49 segments (14%) of 24 patients showed exercise-induced ischemic wall motion abnormalities during cineventriculography. Only 24 of these 49 asynergics (49%) were also detected by 2-D-echo. Using cross-sectional echocardiography, ischemia related wall motion abnormalities were best detected laterally and septaly, whereas apical asynergies were identified in 3 of 12 segments only. Thus, the clinical value of exercise 2-D echo as a screening method in patients suspected to have coronary artery disease is limited and restricted to patients with excellent visualization of the left ventricular endocardium. PMID- 3343806 TI - [IgM antibodies to toxic shock syndrome toxin-1 in human sera and human immunoglobulins]. AB - IgM antibodies against toxic shock syndrome toxin-1 (TSST-1) in 1990 human sera and in 14 human immunoglobulin preparations were determined using an enzyme linked immunosorbent assay. High levels of IgM antibody titres could be found beginning with the third month of life within the first 5 years of age. They were also very common in the age group of 21 up to 25 years. In no case of IgM antibodies with titres higher than 1:251 symptoms could be observed as described for toxic shock syndrome. Of the human immunoglobulin preparations, Pentaglobin contained IgM antibodies against TSST-1 only. The results show that most of the infections with TSST-1 producing Staphylococcus aureus are of subclinical nature or are of less dramatic course than the commonly known toxic shock syndrome. PMID- 3343807 TI - [A discussion group in geriatric psychiatry]. PMID- 3343805 TI - Chronic HIV encephalitis--II. Clinical aspects. AB - Combined medical, neurological, and serological investigations were carried out in 59 patients infected with human immunodeficiency virus (HIV). In stage I clinical and neuropsychiatric testing did not reveal evidence for HIV encephalitis as diagnosed by local antibody production in CSF. Neuropsychiatric abnormalities, brain atrophy, memory and cognitive impairment reliably indicated HIV encephalitis in later stages. The commonest symptoms were cerebellar and brainstem signs, followed by dementia. Epileptic fits and hemiparesis always were associated with cerebral toxoplasmosis. A polyneuropathy was frequently found but other causes have to be considered. PMID- 3343808 TI - [9th Swiss meeting of nurses in oncology. Family, friends and the nurse]. PMID- 3343809 TI - [Mitigating lack of personnel and absenteeism by organizing pools of temporary nurses]. PMID- 3343810 TI - [Nurses may also be patients...]. PMID- 3343811 TI - [Geneva accepts the initiative "Patient's Rights". What are the consequences of approval?]. PMID- 3343812 TI - [The image of child welfare nurses is changing: counseling instead of teaching]. PMID- 3343813 TI - [The five senses]. PMID- 3343814 TI - [Therapeutic-pedagogic services have 4 major wishes from the child welfare nurses]. PMID- 3343815 TI - [Successful nursing convention]. PMID- 3343816 TI - [The nursing process is the tool which safeguards holistic nursing. Planning instead of sacrifice]. PMID- 3343817 TI - [Continuing education: "Introduction to clinical teaching". Well educated--is half won]. PMID- 3343818 TI - [Propaganda product: health promotion]. PMID- 3343819 TI - [Assertiveness: believe in yourselves!]. PMID- 3343820 TI - Characteristics of the spontaneous gastric endocrine tumor of mastomys. AB - Mastomys is a rodent which has been reported to develop spontaneous antral endocrine tumors with acid hypersecretion and duodenal ulceration. This study documents the establishment of a breeding colony and the characterization of the tumors and their possible secretagogues. Parietal cell secretory characteristics were studied using isolated gastric glands (IGG) of both normal (n = 5) and tumor bearing animals. Tumors (n = 6) and control gastric tissue samples were examined by light transmission microscopy and immunohistochemistry. Gastrin was measured by radioimmunoassay in both plasma and tissue. IGG were prepared by collagenase dispersion and acid sequestration assessed by [14C]AP accumulation. Secretory mechanisms of this species were identified by establishment of a histamine dose response curve and use of 8-bromo-cAMP. Receptor and proton pump inhibitions were assessed using cimetidine (10(-5)M) and the H/K ATPase inhibitor omeprazole (10( 5]. Both reduced [14C]AP accumulation significantly (P less than 0.05). 8-Bromo cAMP and histamine significantly stimulated [14C]AP accumulation (P less than 0.05). Although parietal cells were substantially increased in tumor animals as compared to controls, the physiological parameters of acid secretion appeared normal in both and were comparable to other species which have been studied. Tumors were Grimelius positive and contained diffuse electron-dense granules. Immunohistochemistry was negative for gastrin, bombesin, serotonin, neuron specific enolase, calcitonin, and pancreatic polypeptide. Tumor histamine-like immunoreactivity was, however, positive. Normal stomach contained 1001 +/- 185 compared to less than 0.5 pmole/g gastrin in tumors. Plasma gastrin was normal in both groups (29 +/- 5) as compared to 26 +/- 8 pmole/liter. This study characterizes a spontaneous gastric endocrine tumor which is associated with apparent parietal cell hyperplasia and reports of increased acid secretion and duodenal ulceration. The observations are consistent with the elaboration by the tumor of a nongastrin acid-trophic secretagogue. PMID- 3343821 TI - Preservation of myocardial high energy phosphates during cardioplegic arrest with nifedipine. AB - Nifedipine used both as an additive to cardioplegia solution (CPS) and as pretreatment prior to arrest was studied in a rat model to determine its effect upon ischemic ventricular electromechanical work during arrest and upon high energy phosphate levels. Fifty-one normothermic rats were studied in vivo with infusion of hypothermic (4 degrees C) CPS into the cross-clamped aortic root according to one of the following eight protocols: Group 1, baseline beating hearts; Group 2, CPS containing 15 mEq potassium chloride/liter (KCl/liter); Group 3, CPS containing 30 mEq KCl/liter; Group 4, CPS containing 15 mEq KCl/liter combined with stimulation of the vagus nerve; Groups 5 and 6, CPS with 15 mEq KCl/liter and containing 250 or 500 micrograms of nifedipine per liter; Groups 7 and 8, pretreatment with 100 or 200 micrograms nifedipine/kg given as an intravenous bolus 15 min prior to infusion of CPS with 15 mEq KCl/liter. Time to arrest, number of ischemic ventricular contractions after aortic cross clamping, and ATP and creatine phosphate (CP) levels were recorded. All nifedipine groups arrested more quickly and with fewer ventricular contractions and had ATP and CP levels higher than those of Group 2 (P less than 0.05). There were no differences between the nifedipine groups and Group 3 except that Group 8 (200 micrograms/kg pretreatment) resulted in higher levels of CP than Groups 3, 5, and 6 (P less than 0.05 for all groups). When all groups were combined, time to arrest correlated negatively with ATP (r = -0.863, P less than 0.01) and CP (r = -0.824, P less than 0.01) levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343822 TI - Epidural-evoked potentials: a more specific indicator of spinal cord ischemia. AB - The purpose of this experimental study was to examine the differences between peripheral nerve stimulation and direct spinal stimulation in generating cortical somatosensory-evoked potential (SEP) responses for monitoring spinal cord ischemia during thoracic aorta cross-clamping. Adult mongrel dogs (n = 6) were placed under general anesthesia and a left thoracotomy was performed. A conventional stimulating electrode was placed over the posterior tibial nerve (PN SEP), and a special bipolar electrode was placed epidurally over the spinal cord at L1-2 (SC-SEP). The aorta was cross-clamped proximal to the left subclavian artery. Stimulations were alternately performed through both electrodes, and SEP responses were continuously monitored. The cross-clamp was released after one hour and the animal was observed for another hour prior to sacrifice. Excellent SEPs were obtained with six stimuli over 3 sec via the SC-SEP stimulus in contrast to the 200 stimulations over 90 sec required for the PN-SEP stimulus. Aortic cross-clamping resulted in a significantly longer mean time to loss of SEPs for SC-SEP (mean +/- SEM, 13.7 +/- 1.0 min for SC-SEP vs 11.3 +/- 0.7 min for PN-SEP, P less than 0.05). Likewise, unclamping of the aorta consistently resulted in a shorter mean time to return of SEPs for SC-SEP compared with PN SEP. These data indicate that direct epidural stimulation for evoked cortical responses is a more sensitive means of determining the adequacy of posterior spinal cord blood flow as reflected by posterior spinal cord function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343823 TI - Association of cholecystectomy with pancreatic growth and increased plasma levels of cholecystokinin in the Syrian golden hamster. AB - This study examined the effect of cholecystectomy on plasma concentrations of cholecystokinin (CCK) and pancreatic growth. Seventy female Syrian golden hamsters were used in the investigation. Half the animals underwent cholecystectomy and half had a sham procedure. Following cholecystectomy, significant increases were observed in pancreatic weight (11-41%), total DNA content (8-16%), total protein content (9-19%), DNA synthesis rate (57-200%), and in random plasma CCK concentrations (12-81%) in comparison to the control group. There was no significant change in protein synthesis rate. We conclude that cholecystectomy may have a significant trophic effect on the pancreas and that this effect may be mediated by an increase in circulating levels of CCK. PMID- 3343824 TI - Mechanical and histologic changes in canine vein grafts. AB - Mechanical and histological studies were performed on dog femoral veins after their implantation as grafts to bypass the ligated femoral arteries. The vein grafts dilated rapidly after implantation with 90% of maximum dilation occurring at 4 weeks. Both the native veins and the vein grafts were highly compliant up to 35-50 mm Hg, but were virtually nondistensible at higher pressures. When implanted with end-to-side anastomoses (end of vein to side of artery), the compliance of the anastomotic region resembled that of the artery rather than that of the vein. This was due to the distensibility of the artery at arterial pressure, as compared with the almost rigid vein. Histologic examination showed that intimal hyperplasia was greater after end-to-side anastomosis than after end to-end anastomosis (P less than 0.05) and that this increased hyperplasia was reduced by treatment with aspirin and dipyridamole (P less than 0.05). By contrast, medial thickening was increased in all grafts compared with native veins (P less than 0.05), but was not different in end-to-end, end-to-side, and aspirin/dipyridamole-treated end-to-side grafts. These data suggest that intimal hyperplasia and medial thickening are separate responses to different stimuli. PMID- 3343826 TI - Alcohol withdrawal. PMID- 3343825 TI - Muscle high energy phosphates in chronic peripheral vascular disease. AB - There is little information available concerning the alterations in skeletal muscle energy metabolism which occur in response to chronic arterial occlusive disease. In addition, the effect of arterial reconstruction on skeletal muscle energy metabolism in patients with peripheral vascular disease has not been defined. Needle biopsies were obtained from the quadriceps femoris muscle of 7 patients with aortoiliac disease and 15 patients with femoropopliteal disease and from the gastrocnemius muscle of 9 patients with femoropopliteal disease. Muscle samples were analyzed for ATP, ADP, AMP, phosphocreatine, creatine, and lactate. Eleven patients were rebiopsied after vascular reconstruction. Patients with rest pain had decreased total adenine nucleotides, energy charge potential, and ATP/ADP ratios as compared to those of controls. ATP levels were significantly decreased in muscle samples obtained distal to the arterial occlusion (i.e., quadriceps/aortoiliac, gastrocnemius/femoropopliteal) in patients with rest pain (compared with controls). ATP levels did not differ significantly from those of controls in muscle samples obtained from patients with claudication. However, energy charge potential was significantly decreased in all patients with claudication regardless of biopsy site and location of arterial occlusive disease. Normalization of muscle energy metabolism was not demonstrated following arterial reconstruction. We conclude that resting skeletal muscle energy metabolism is abnormal in patients with chronic arterial insufficiency and that progression of disease toward more severe ischemia is associated with more marked derangement. Whether the possible beneficial effects of revascularization on muscle energy metabolism are masked by the concurrent effect of injury in the early postoperative period remains to be clarified. PMID- 3343827 TI - A young man with meningitis and purpura. PMID- 3343828 TI - A public health perspective on violent death. PMID- 3343829 TI - The AIDS dilemma. PMID- 3343830 TI - AMA CEJA report A. PMID- 3343831 TI - Friends of the NLM. PMID- 3343832 TI - The distribution of primary care physicians in Tennessee. PMID- 3343833 TI - Home health vs. nursing home care. PMID- 3343834 TI - Ethical issues involved in the growing AIDS crisis. PMID- 3343835 TI - Medicine, the compassionate profession. Tennessee, the volunteer state. PMID- 3343836 TI - Primary breast cancer in patients with previous endometrial or ovarian cancer. AB - The incidence of primary breast cancer is known to be increased in patients with previous endometrial or ovarian cancer, but the behavior of the breast cancer and the ultimate outlook for such patients is unknown. To provide data concerning these two questions, a group of 123 patients treated for breast cancer alone (Group I) served as a control for comparison with ten patients who had endometrial cancer (Group II) and six patients who had ovarian cancer (Group III) prior to diagnosis of breast cancer. The interval between the diagnosis of endometrial cancer and breast cancer averaged 4.6 yr, and between ovarian cancer and breast cancer, 5.4 yr. Age at diagnosis of breast cancer in Groups I, II, and III was 56, 66 (P = 0.05) and 56 yr, respectively. The incidence of patients with stage I, II, and III breast cancer was similar in Groups I, II, and III as was tumor size and number of metastatic nodes in each stage in each of the three groups. Average duration of follow-up after diagnosis of breast cancer was 3, 3.1, and 2.8 yr in Groups I, II, and III, respectively, with 70%, 60%, and 33% of patients living and free of either breast cancer, endometrial cancer, or ovarian cancer. Two of four deaths in Group II were due to endometrial cancer, and all four deaths in Group III were due to ovarian cancer. The remaining two deaths or recurrences in Group II were due to breast cancer. We conclude that 1) the behavior of breast cancer is similar in patients with or without previous endometrial or ovarian cancer; 2) breast cancer develops at an older age in patients with previous endometrial cancer than in patients with or without previous ovarian cancer and 3) death or recurrent cancer in patients with breast cancer and previous ovarian cancer is due to ovarian cancer, whereas, death or recurrent cancer in patients with breast cancer and previous endometrial cancer is due equally to breast cancer and endometrial cancer. PMID- 3343837 TI - Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysis. AB - Intraoperative radiotherapy (IORT) has been utilized in the treatment of resectable and unresectable pancreatic carcinoma at the National Cancer Institute. Detailed autopsy analyses of the radiation effects on the pancreas and adjacent tissues were performed on 13 patients dying at various times following therapy. IORT can induce a progressive retroperitoneal fibrosis and fibrosis of the porta hepatis in patients with resectable pancreatic carcinoma. In unresectable pancreatic carcinoma, the major expression of intraoperative irradiation with external beam irradiation is a progressive fibrosis of the pancreas with vascular sclerosis, nerve degeneration, atrophy of acinar cells, and atypical changes in the ducts of the pancreas, as well as degenerative changes of the pancreatic tumor. PMID- 3343838 TI - Regression analyses of prognostic factors in colorectal cancer. AB - In a follow-up study of 110 patients with colorectal cancer, age, sex, erythrocyte sedimentation rate (ESR), hemoglobin (Hb), leukocyte count, emergency operation, tumor site, Dukes' stage, and histologic grade were tested in survival analyses. Dukes' stage was a highly superior prognostic discriminator. In multivariate survival analysis (Cox model) elevated ESR and leukocytosis were significant prognostic factors in addition to the Dukes' stage, indicating high risk patients with shorter survival. PMID- 3343839 TI - The effect of prior adjuvant chemotherapy on survival in metastatic breast cancer. AB - Some adjuvantly treated patients develop recurrent breast cancer and little is known about the effect of prior adjuvant chemotherapy on subsequent response rates to systemic therapy or on overall survival. We describe our retrospective comparison of 179 patients who received doxorubicin containing adjuvant chemotherapy and developed recurrent breast cancer on University of Arizona Cancer Center clinical trials with 202 non-adjuvantly treated patients entered onto clinical protocols for recurrent or metastatic breast cancer during the same period. Adjuvant failures had a shorter median survival from the date of onset of recurrent disease (18 months versus 28 months, P less than 0.001), a lower response rate to initial combination chemotherapy (38% versus 69%, P = 0.001), and a high incidence of CNS involvement at the time of relapse (11%). In patients having recurrent or metastatic breast cancer, a history of prior adjuvant chemotherapy appears to identify a subgroup who will have a higher incidence of CNS involvement, a lower response rate to chemotherapy and a shorter survival with metastatic disease. These findings may help explain the failure of improved relapse free survival seen in many adjuvant chemotherapy trials to result in improved overall survival. PMID- 3343840 TI - Merkel tumor of the lower lip: a case report and updated review of the literature work performed at the University of Illinois. AB - An unusual case of Merkel cell carcinoma of the lower lip with metastasis to the submental nodes is presented. Clinical similarities and the histopathologic and prognostic differences between this tumor and basal or squamous cell carcinomas of the head and neck area are discussed and the current thoughts for treatment are presented. The capricious clinical course and the aggressive nature of the Merkel cell tumor is emphasized. A review of the existing literature is also included in an effort to familiarize the head and neck surgeon with this relatively new but potentially lethal pathological cutaneous entity. PMID- 3343841 TI - Silicone elastomer catheter for chronic vascular access. AB - The Evanston and Glenbrook Hospitals' series of 157 consecutive silicone elastomer central venous catheter insertions is reviewed. The total experience was 12,721 patient days (34.85 patient years). The complication rate of insertion was 1.91%, but no patient required chest tube drainage. Seven catheters clotted and could not be salvaged. Seventeen catheters were removed for suspected bacterial infection. Peripheral blood culture was not predictive of catheter tip contamination, while culture of blood drawn through the catheter and insertion site cultures proved most useful. Five bona fide infections were documented for an infection rate of 3.18%. This corresponds to one infection per 2,544 patient days (6.97 patient years). The mean duration of service of the catheter was 81 days with a median of 36 days. The longest duration was 707 days. The silicone elastomer catheter provides safe, dependable venous access for most patients and may be inserted in an outpatient and therefore cost-effective setting. PMID- 3343842 TI - Late recurrence of benign pheochromocytomas: the necessity for long-term follow up. AB - Two patients who had removal of seemingly benign pheochromocytomas had recurrences 10 and 14 years later despite normal catecholamine excretion for 7 and 9 years postoperatively. The first patient returned with a myocardial infarction and an apparently solitary recurrence; the second patient with a stroke and metastatic disease. Both patients had recurrence of hypertension and increased catecholamine excretion. They were given phenoxybenzamine and are doing satisfactorily 7 and 9 years after their recurrences. Such patients should be followed after surgery for 15 or more years for early detection of recurrences. Prompt therapy should reduce the risk of undesirable complications. PMID- 3343843 TI - Post-circumcision carcinoma of the penis: II. Surgical management. AB - Post-circumcision penile carcinoma is a unique clinical entity that occurs in circumcision scars on the penile shaft. Excision is the only effective treatment. Surgical excision must be tailored to the wide spectrum of disease extension. While some primary tumors can be controlled by standard penectomy, others may require much more extensive resection while some can be adequately controlled without sacrificing the urethra or the corpora. Those who had a conservative operation for less extensive disease had the best results. PMID- 3343844 TI - Carcinoma of the nasopharynx in Northern Israel: epidemiology and treatment results. AB - Between 1968 and 1984, 49 patients with carcinoma of the nasopharynx were treated at the Northern Israel Oncology Center. There were 6 stage I-II patients (12%) and 43 stage III-IV patients (88%). According to ethnic origin, there were 27 (55%) non-Ashkenazi Jews, 9 (18%) Ashkenazi Jews, and 13 (27%) Arabs. This distribution is different from the percentages of these ethnic groups in Northern Israel. All patients received combined cobalt 60 and 8-10 MeV electron beam radiotherapy to the primary tumor and the entire neck. Twelve stage III-IV patients received three courses of chemotherapy using bleomycin, methotrexate, and cisplatin (BMP) prior to definitive radiotherapy. The following 5-yr actuarial survival figures were achieved: all patients, 42%; stage I-II, 63%; stage III-IV, 37%; Arabs, 53%, non-Ashkenazi Jews, 47%; Ashkenazi Jews, 22%; BMP+radiotherapy, 54%; radiotherapy alone, 42%. It is concluded that there is an ethnic-related pattern of nasopharyngeal carcinoma in Northern Israel. Prognosis is better in non-Ashkenazi Jews and Arabs with early-stage lymphoepithelioma or anaplastic carcinoma, younger than 45 yr old, and receiving more than 5,500 cGy. Chemotherapy by BMP improves initial control rates with questionable benefit to long-term survival. PMID- 3343845 TI - Hormone receptors in breast cancer: a conservative determination of receptors' presence in tumor tissue and ipsilateral normal mammary gland. AB - Estrogen (ER) and progesterone (PgR) receptors were evaluated in the tumor tissue (T) and in the mammary gland far from malignancy (D) in 36 breast cancers. Results were correlated with the pathological grading of the tumor and the axillary nodal status. It is suggested that a lower cancer malignancy with negative nodes and lower values of pathological grading (G1-G2) may be associated with a high level of ER in the mammary parenchyma far from the tumor (D). PMID- 3343846 TI - Intraperitoneal infusion of 5-FU in liver metastases from colorectal cancer. AB - Intraperitoneal 5-fluorouracil (5-FU) was given to eight patients with unresectable colorectal liver cancer and to one patient after radical hepatectomy. A subcutaneous intraperitoneal access device was implanted, and treatment consisted of continuous infusion of 1,000 mg 5-FU/d for 5 days, repeated every 6 weeks. Evaluation of treatment was performed after every two cycles of therapy. A total of 32 infusion cycles were given. The mean steady state concentration of 5-FU was 0.56 +/- 0.04 mumol/l (mean +/- SEM), and the total body clearance was 10.0 +/- 0.71/min mean +/- SEM). The levels of 5-FU in peripheral venous blood were stable and reproducible. When incubated in whole blood at 37 degrees C the concentration of 5-FU fell rapidly and after 2 h, only 22% of the starting level remained. When kept ice-cold, 5-FU samples were stable. Patient acceptance was excellent, and the therapy was free from complications except for slight abdominal discomfort, not enough to require alleviation by analgesic drugs. Computerized tomography (CT) scan showed stationary tumor volume after two cycles of therapy in four of eight patients who could be evaluated. It is concluded that continuous intraperitoneal infusion of 5-FU produces stable and reproducible levels of the drug in peripheral venous blood, that 5-FU is degraded by blood cells at 37 degrees C, that the use of a subcutaneous access device makes the delivery easy and safe, and that the efficacy of the therapy seems to be similar to that obtained with hepatic arterial infusion. PMID- 3343847 TI - The impact of distal aortic perfusion and somatosensory evoked potential monitoring on prevention of paraplegia after aortic aneurysm operation. AB - Temporary distal aortic perfusion and somatosensory evoked potential monitoring were attempted prospectively in 198 patients to prevent neurologic complications from occurring after operation for descending thoracic and thoracoabdominal aortic aneurysm. These 198 patients were divided into two groups. Group 1 consisted of 99 (50%) patients in whom adequate (60 mm Hg) distal bypass was achieved and combined with somatosensory evoked potential monitoring. Group 2 consisted of 99 (50%) in whom this could not be achieved. Of the latter, four patients were excluded because of operative death in one and preexisting neurologic deficits in three. The rates of early and delayed neurologic complications were 8% and 12%, respectively, in the former and 7% and 8%, respectively, in the latter. Using the logistic regression method of statistical analysis, adjusting for the difference in patient mix, we found no statistical difference in the incidence of neurologic complications in the two groups. The incidence of false negative somatosensory evoked potential response was 13% and false positive response 67%. Localization of critical spinal arteries for reattachment was not possible. Thus, the method had no significant impact upon the prevention of neurologic deficits, which varied from mild or transient to severe and which either occurred during the operation or were delayed from 12 hours to 21 days. PMID- 3343848 TI - Esophagectomy for complex benign esophageal disease. AB - We evaluated the use of total thoracic esophagectomy and replacement with stomach in a group of 21 patients between 1976 and 1986 who had undergone multiple unsuccessful esophageal operations. All patients had between one and four unsuccessful operations for benign esophageal disorders. Sixteen patients had primary motor disorders: achalasia in nine and esophageal spasm in seven. Of these patients, 11 also had recurrent gastroesophageal reflux and peptic esophagitis. Complicated reflux disease characterized by severe esophagitis, stricture, and impaired peristalsis without primary motor disorder occurred in five patients. In one patient a functionally impaired long-segment colon interposition was removed and replaced with stomach. Total thoracic esophagectomy and cervical esophagogastric reconstruction was done in all patients. The transhiatal approach was chosen for resection in 16 patients and thoracotomy was used in the other five. There was one perioperative death (5%), from massive aspiration 4 days after transhiatal esophagectomy. Other complications included transient anastomotic leak (three patients), tracheoesophageal fistula (one), recurrent nerve palsy (one), and transient hoarseness (two). Follow-up is complete between 1 and 10 years and reveals the following functional results: 12 patients good to excellent, seven fair, one poor. In this patient group in which multiple prior procedures have failed to improve severe incapacitating symptoms, we believe further attempts at hiatal reconstruction are unlikely to succeed. For this circumstance, we recommend total thoracic esophagectomy with the use of stomach as the replacement organ of choice. PMID- 3343849 TI - Reduction in sudden late death by concomitant revascularization with aortic valve replacement. AB - To determine the impact of coronary atherosclerosis and myocardial revascularization on survival after aortic valve replacement, we reviewed our experience with single aortic valve replacement between 1969 and 1984. Of 474 patients (mean age 62 +/- 13 years), 185 (39%) had no associated coronary artery disease, 233 (49%) had coronary artery bypass grafting, and 56 (12%) had unbypassed coronary artery disease. Early (30-day) mortality rates were 2.2%, 8.2%, and 7.1%, respectively (p less than 0.01, coronary disease absent versus present). Actuarial survival rates at 10 years were 77% +/- 4%, 41% +/- 6%, and 26% +/- 11% (p less than 0.001, coronary disease absent versus present), with 1 to 177 months of follow-up (mean 56 +/- 40). Preoperative angina (39%) did not predict the presence of coronary artery disease (61%). Multivariate logistic regression analysis showed that early deaths were associated with advanced preoperative New York Heart Association functional class (p less than 0.001), advanced age (p less than 0.05), more extensive coronary artery disease (p less than 0.05), and lack of cardioplegic myocardial protection (p less than 0.05). Complete revascularization did not increase operative risk when coronary artery disease was present (early mortality 6.8%, p = not significant). Late deaths were strongly associated with the presence of coronary artery disease (p less than 0.001) and reduced left ventricular ejection fraction (less than or equal to 55%, p less than 0.01). Late cardiac mortality was most commonly attributable to sudden death (30/71, 42%), especially in the unbypassed coronary disease cohort (9/14, 64%). The actuarial rate of freedom from sudden death at 10 years was 52% +/- 17% in the unbypassed coronary artery disease group (p = 0.009), compared with 90% +/- 3% and 91% +/- 3% in the revascularized and no coronary disease patients, respectively. Thus, coexistent coronary atherosclerosis has a detrimental impact on early and late survival after aortic valve replacement. Revascularization does not increase operative risk when associated coronary artery disease is present and significantly reduces the occurrence of late sudden death. Strategies that minimize operative risk when associated coronary artery disease is present include use of cardioplegia and complete revascularization. PMID- 3343850 TI - Improved results of surgical treatment for esophageal and gastroesophageal junction carcinomas after preoperative combined chemotherapy and radiation. AB - Combined treatment with chemotherapy and radiation (chemoradiation) preceding surgical exploration for esophageal or gastroesophageal squamous cell carcinoma or adenocarcinoma was compared with surgical exploration alone to determine if there was an influence on tumor status at exploration, tumor resectability, disease recurrence, and patient survival. Preoperative chemoradiation resulted in significant tumor response as measured by decreased nodal involvement and 36% incidence of no residual tumor at resection (total response) and was reflected by an improvement in resectability. Local tumor recurrence was eliminated by preoperative chemoradiation preceding resection. Distant recurrence was not reduced and remained the major cause of death. The 2-year survival rate after tumor resection alone was 33% versus 66% after preoperative chemoradiation and resection (p = 0.13). Patient survival after resection alone was predicted by pathologic extent of local disease as measured by lymph node status. In contrast, survival after chemoradiation and resection was not predicted by pathologic extent of local disease. Surgical resection appears to have been an important component of therapy, primarily because survival was improved in patients after resection of residual local disease. PMID- 3343851 TI - Clinical and hemodynamic results of cardiac valve replacement with the Monostrut Bjork-Shiley prosthesis. AB - Between May 1983 and April 1986, 318 patients underwent cardiac valve replacement with the Monostrut Bjork-Shiley prosthesis. There were 136 aortic valve replacements, 128 mitral valve replacements, and 54 multiple replacements. A total of 373 valves were implanted. Associated procedures were done in 79 (25%) of the patients. Hospital (30-day) mortality rate was 5.6% (18 patients): 2.9% (n = 4) after aortic, 7.8% (n = 10) after mitrals and 7.4% (n = 4) after multiple valve replacement. Follow-up was obtained in all 300 operative survivors, for a total of 500 patient-years (mean 18 months). Actuarial survival rate, excluding operative deaths, at 4 years was 94.7% +/- 1.5% (mean +/- standard error of the mean). There were 16 thromboembolic episodes (3.2/100 patient-years). Freedom from all valve-related complications was 87% +/- 2.4% at 3 1/2 years. Neither valve thrombosis nor structural failure has been observed. Eighty percent of the patients are in New York Heart Association functional class I. Forty-two patients (26 with aortic and 16 with mitral valve replacement) underwent cardiac catheterization a mean of 6 1/2 months after the operation. In the aortic position, peak gradients were an average of 6.9 +/- 1.2 mm Hg. Mean systolic gradients were 12.4 +/- 6.3 mm Hg and did not increase with exercise. In the mitral position, end-diastolic gradients were an average of 2.1 +/- 2 mm Hg and mean gradients, 5.9 +/- 2 mm Hg. Discharge coefficient (estimated orifice area/geometric area) was 0.63 +/- 0.2 for the aortic and 0.53 +/- 0.2 for the mitral prostheses. Disc opening was maximal in most patients. These results indicate that the Monostrut prosthesis has a low rate of thromboembolic events, no structural failures or thrombotic obstructions and excellent hemodynamic performance, especially in the small aortic sizes (discharge coefficient for 19 and 21 mm valves, 0.77). PMID- 3343852 TI - The importance of load-independent analysis in assessment of the inotropic effect of prostaglandin E1 in vivo. AB - Load-independent pressure-dimension analysis was applied in 13 open-chest, anesthetized dogs during either left atrial (n = 7) or right atrial (n = 6) infusion of prostaglandin E1. Right atrial infusion of prostaglandin E1 in doses from 31 to 500 ng/kg/min resulted in no change in any parameters studied, including mean arterial pressure, cardiac output, and systemic and pulmonary vascular resistances. Left atrial infusion of prostaglandin E1 produced dose dependent reductions in mean arterial pressure and systemic vascular resistance but no change in the slope of the relationship of left ventricular stroke work to end-diastolic length, a load-independent index of ventricular performance. In contrast to findings obtained with load-dependent parameters, these results suggest that prostaglandin E1 has no positive inotropic effect in vivo. PMID- 3343853 TI - Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Effect of unprotected and protected global ischemia. AB - Previous studies noted augmented postischemic myocardial oxygen consumption as a subtle indicator of ischemic injury in the isovolumically contracting left ventricle. The present study was done to determine if the linear relationship between oxygen utilization and stroke work present in the ejecting heart would facilitate compartmentalization of this increased oxygen consumption into resting and working metabolic demands. Therefore, 18 canine hearts instructed for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during incremental volume infusion while undergoing right heart bypass. Data acquisition before and after either 20 minutes of 37 degrees C global ischemia or 2 hours of 20 degrees C cardioplegic arrest allowed construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least squares regression analysis. Although contractility was depressed 48% (p less than 0.01) after unprotected ischemia and was unchanged after cardioplegic arrest, neither group demonstrated a change in the efficiency of converting consumed oxygen to external mechanical work. In contrast, in both groups the oxygen utilization for unloaded contraction was comparably augmented by 21% and 16% (p less than 0.05), despite the varying ischemic conditions and disparate preservation of contractile function. These data suggest a highly linear correlation between oxygen consumption and external mechanical work that persists after ischemia and discriminates the components of postischemic energetic derangements. This model may be useful in the development and assessment of specific myoprotective strategies. PMID- 3343854 TI - Repair of congenitally malformed mitral valve in children. AB - We report our experience with 30 children under 15 years of age treated surgically for congenital mitral valve disease from March 1972 to July 1986. Valve reconstruction was possible in 26 patients (87%), whereas in four the valve was replaced with a mechanical prosthesis. Five patients died in the hospital (16.6%), four after conservative operations and one after mitral valve replacement. There was only one late death in a child in chronic congestive heart failure. Three patients, treated conservatively, required valve replacement 2, 22, and 24 months, respectively, after the operation. Follow-up data reveal that 22 of 24 patients are asymptomatic 5 months to 15 years after operation. Two dimensional echocardiographic studies were performed in 19 patients treated conservatively, 17 of whom are asymptomatic. Eleven of them have no signs of mitral regurgitation or stenosis, six show only mild mitral incompetence, and two have moderate mitral regurgitation or stenosis. Peak pulmonary artery pressure is within normal limits in all. Our results indicate that mitral valve reconstructive procedures for congenital valve dysplasia may be effective and reliable in children despite the frequent severity of valve malformation. Although no major prosthesis-related complications were observed in the present series, we believe that mitral valve repair should always be attempted in the pediatric population to avoid the drawbacks of the currently available prostheses. PMID- 3343855 TI - Infundibular septal resection: surgical anatomy of the superior approach. AB - A technique for extensive resection of the infundibular septum through the superior transarterial approach is proposed. Infundibular septal resection facilitates intraventricular rerouting for anatomic correction of transposition of the great arteries with ventricular septal defect and double-outlet right ventricle. This technique also may be used to enlarge progressively obstructive but physiologically advantageous ventricular septal defects, for example, with tricuspid atresia. Through the superior transaortic or transpulmonary approach, the landmarks of the infundibular septum are the intercoronary commissure of the aortic valve and the septal commissure of the pulmonary valve, both of which are directly above the middle of the infundibular septum. With this exposure, the infundibular septum may then be resected easily and relatively completely and a large opening created immediately beneath the semilunar valves. The feasibility of infundibular septal resection by the superior approach was assessed post mortem in 25 cases of transposition of the great arteries with ventricular septal defect and in 20 autopsied cases of double-outlet right ventricle. This technique was subsequently applied successfully to enlarge the obstructive ventricular septal defect of a 2-year, 11-month-old girl with D-transposition of the great arteries. The advantages of the proposed technique include technical ease, relative completeness of infundibular septal resection, and the facilitation of intraventricular repair of transposition of the great arteries with ventricular septal defect and double-outlet right ventricle. PMID- 3343856 TI - Predictors of failure after endocardial resection for sustained ventricular tachycardia. AB - This study was designed to identify characteristics that might be predictors of failure of surgical treatment alone (endocardial resection) for sustained ventricular tachycardia. Thirty-three consecutive patients with sustained ventricular tachycardia were studied by standard techniques preoperatively, intraoperatively, and 7 to 36 days postoperatively. Standard endocardial resection was guided by intraoperative mapping in all patients. Adjuvant cryoablation was used in areas that were not accessible to excision. Patients were divided into two groups on the basis of the results of the postoperative electrophysiologic study. Group I (14) were patients who still had ventricular tachycardia (failure) and Group II (19) were those who did not have ventricular tachycardia (success). On the basis of the postoperative electrophysiologic testing, the time from myocardial infarction to surgical treatment (less than 3 months) was a powerful predictor of failure of operation alone to prevent ventricular tachycardia (p less than 0.01). This may indicate a different mechanism of ventricular tachycardia in this group of patients. Another possible predictor of surgical failure was three-vessel disease. The site of origin of ventricular tachycardia, the use of cryoablation, the number of morphologies, and the amount of tissue resected were not significant predictors of success or failure. The result of the postoperative electrophysiologic study was also a strong prognostic predictor of subsequent arrhythmias. PMID- 3343857 TI - Effects of left ventricular venting and distention during heterogenous distribution of cardioplegic solution. AB - The effects of left ventricular venting and distention on myocardial protection during heterogenous distribution of cardioplegic solution remain undefined. This study was undertaken to determine if left ventricular venting enhances and distention impairs myocardial cooling and recovery of global and regional left ventricular function. Twenty-one pigs were placed on cardiopulmonary bypass and subjected to 80 minutes of ischemic arrest with the mid-left anterior descending artery occluded. Hearts were protected with multidose potassium (25 mEq/L) crystalloid cardioplegic solution supplemented with topical (4 degrees C) and systemic (28 degrees C) hypothermia. During arrest, the left ventricle was vented in seven pigs, seven pigs were not vented, and seven others had systemic pump blood infused into the left ventricle to maintain an end-diastolic pressure of 15 mm Hg. Parameters measured included left ventricular temperature, stroke work index, compliance (end-diastolic pressure-end-diastolic volume curves) and wall motion scores (two-dimensional echocardiography). Distended hearts had the lowest mean left ventricular temperature beyond the left anterior descending arterial occlusion (10.1 degrees +/- 1.8 degrees C distended [p less than 0.025 from vented and nonvented groups] versus 14.2 degrees +/- 0.7 degrees C vented versus 15.5 degrees +/- 1.2 degrees C nonvented), the highest postischemic stroke work index (0.78 +/- 0.09 gm-m/kg distended versus 0.62 +/- 0.07 gm-m/kg vented versus 0.66 +/- 0.07 gm-m/kg nonvented at end-diastolic pressure = 10 mm Hg), and the best wall motion scores (0.7 +/- 0.04 distended [p less than 0.025 from vented and nonvented groups] versus 5.5 +/- 1.80 vented versus 4.8 +/- 1.20 nonvented). Postischemic end-diastolic pressure-end-diastolic volume curves were unchanged from preischemic values in each group. We conclude that during heterogenous cardioplegic arrest, left ventricular venting offers no additional myocardial protection and may negate the beneficial effects of moderate (end-diastolic pressure = 15 mm Hg) left ventricular distention. PMID- 3343858 TI - Elevated coronary sinus pressure does not alter myocardial blood flow or left ventricular contractile function in mature sheep. Implications after the Fontan operation. AB - The hypothesis that elevation of coronary sinus pressure affects coronary blood flow and ventricular function was tested in this study of seven adult ewes placed under pentobarbital anesthesia. Coronary sinus pressure was elevated by partial balloon occlusion. Right atrial, left atrial, and aortic mean pressures and rate of rise of left ventricular pressure were measured. Coronary blood flow was determined with radioactive microspheres. Studies were performed at control and at moderate (15 to 20 mm Hg) and marked (30 to 35 mm Hg) elevation of coronary sinus mean pressures. Despite increase of coronary sinus pressure from a control value of 2 mm Hg +/- 1 to levels of 19 mm Hg +/- 1 and 34 mm Hg +/- 1, no significant changes were observed in right atrial, left atrial, or aortic mean pressure or rate of rise of left ventricular pressure. Both endocardial and epicardial blood flows were unaffected. The endocardial/epicardial flow ratio at moderate coronary sinus pressure elevation was significantly increased, which suggested local subendocardial vasodilation in the absence of changes in transmural perfusion. The findings suggest that isolated increase in coronary sinus pressure is not a major determinant of myocardial blood flow or ventricular performance in the normal ewe. PMID- 3343859 TI - Intraoperative two-dimensional Doppler echocardiography. A preliminary study for congenital heart disease. AB - Intraoperative two-dimensional echocardiograms were performed in 30 patients (group I) and two-dimensional Doppler color flow imaging was performed in 30 additional patients (group II) with various forms of congenital heart disease. A comparative complete two-dimensional Doppler and color flow examination was performed in group II patients 10 to 14 days postoperatively. Standard intraoperative two-dimensional echocardiograms demonstrated excellent correlation with preoperative findings and allowed assessment of valvular regurgitation or shunt when combined with echocardiographic contrast injections. However, intraoperative and postoperative two-dimensional color flow imaging was obtained more easily and rapidly and allowed recognition of more postoperative residual defects. Color flow imaging appears to be a useful method for intraoperative assessment of surgical repair of congenital cardiac defects. Twenty-one residual lesions were correctly diagnosed intraoperatively, whereas seven residual lesions were demonstrated only during later postoperative examination. This preliminary experience has also demonstrated several areas for future development and improvement of these techniques. Combined two-dimensional Doppler and contrast echocardiographic studies may allow better disclosure of residual defects. PMID- 3343860 TI - Physiologic determinants of coronary blood flow during external cardiac massage. AB - Adequate coronary blood flow is a major determinant for successful resuscitation from cardiopulmonary arrest. To develop compression techniques that optimize coronary blood flow, we implanted in eight dogs electromagnetic flow probes that measured circumflex coronary blood flow and ascending aortic blood flow. Micromanometers measured left ventricular and aortic pressures. Each dog was anesthetized and intubated, and the heart was fibrillated electrically. High impulse manual chest compressions were performed with the dog in the supine position, and compression rate was varied from 60/min to 150/min. Antegrade coronary blood flow occurred primarily during artificial diastole, and there was a brief period of retrograde coronary blood flow with compression during artificial systole. Cardiac output and diastolic aortic pressure increased with compression rate, significantly augmenting peak coronary blood flow velocity. However, diastolic perfusion time decreased linearly with compression rate and limited coronary perfusion at rates greater than 120/min. As a result, net coronary blood flow during high-impulse manual chest compression was determined primarily by diastolic aortic pressure and diastolic perfusion time. Coronary blood flow was optimized in this model at a compression rate of 120/min. PMID- 3343861 TI - A new instrument to facilitate myectomy in subaortic hypertrophic stenosis. AB - A new instrument, a modified "back-biting" Kerrison rongeur, is presented and recommended for the treatment of hypertrophic subvalvular aortic stenosis. The spike of the instrument allows the instrument to be engaged accurately and effectively into the anterior surface of the muscular ridge and appropriate obstructing tissue to be removed. PMID- 3343862 TI - An unusual lethal complication of preservation of chordae tendineae in mitral valve replacement. AB - In two patients, several chordae tendineae of the mural leaflet were preserved during mitral valve replacement. Hemorrhagic necrosis and spontaneous rupture of the preserved posterior papillary muscle led to disc entrapment and the death of both patients. PMID- 3343863 TI - Bronchial leiomyoma: report of a case successfully treated by endoscopic neodymium-yttrium aluminum garnet laser. AB - A 40-year-old woman was admitted with dyspnea and episodes of bronchial infection. Leiomyoma of the right lateral basal bronchus was diagnosed and partially removed by a biopsy forceps, and neodymium-yttrium aluminum garnet laser therapy successfully destroyed the rest of this mass. PMID- 3343865 TI - Cardiopulmonary bypass and cold agglutinin. PMID- 3343864 TI - Total anomalous pulmonary venous return with left heart hypoplasia. AB - A term baby had a total anomalous pulmonary venous return to the inferior vena cava. The infant underwent complete repair, but died 30 hours after operation. The postmortem examination revealed severe endocardial fibroelastosis. This uncommon association is discussed. PMID- 3343866 TI - Specific chromosomal abnormalities in acute nonlymphocytic leukemia correlate with drug susceptibility in vivo. AB - Specific chromosomal abnormalities are independent predictors of response to therapy in acute nonlymphocytic leukemia (ANLL) de novo. In a series of 149 patients with ANLL, we sought to determine whether the t(8;21), t(15;17), t(9;11) or other abnormalities of the long arm of chromosome 11, inv(16) or t(16;16), inv(3) or t(3;3), trisomy 8, and abnormalities of chromosome 5 (-5/5q-) or of chromosome 7 (-7/7q-) identify differences in susceptibility to chemotherapy drugs in vivo. The immediate outcome of the first cycle of remission induction chemotherapy was analyzed for patients in each cytogenetic subgroup as an index of the drug susceptibility of the leukemia cells in vivo. Patients with t(8;21), inv(16), t(16;16), or 11q abnormalities had high rates of complete remission after initial therapy (60-100%), whereas patients with -7/7q- or -5/5q- had low initial response rates (0-36%), suggestive of drug resistance in vivo. In general, cytogenetic groups with high initial complete remission rates ("drug sensitive") also had long disease-free survivals; those groups with low initial remission rates ("drug resistant") had short remission durations even if these patients eventually achieved complete remission with further therapy. Patients with acute promyelocytic leukemia (APL), all of whom had the t(15;17), were the exception; despite low initial remission rates, they had long disease-free survivals, possibly due to a more rapid cytotoxic effect of chemotherapy on the clonogenic APL cells than on the more numerous malignant promyelocytes. We conclude that the prognostic importance of specific chromosomal abnormalities in ANLL resides in part in differing susceptibilities to chemotherapy. PMID- 3343867 TI - Effect of blood conservation efforts in cardiac operations at the Mayo Clinic. AB - In a retrospective study of 388 patients who had undergone cardiac operations at our institution during two time periods-before (1982) and after (1984) introduction of autologous transfusion-we analyzed the effect of blood conservation efforts and autologous transfusion on blood usage, postoperative complications, and duration of hospitalization. Cell salvage techniques resulted in a significant reduction (P less than 0.0001) in use of not only homologous blood (from a mean of 9.6 units per patient in 1982 to 3.2 units in 1984) but also fresh-frozen plasma and platelet concentrates. We found no significant difference in morbidity or mortality for the two study periods. Although the mean duration of hospitalization decreased from 11.7 days in 1982 to 9.6 days in 1984, this change was probably related to factors other than the introduction of blood conservation efforts. Thus, techniques used to decrease the amount of blood replacement needed for cardiac surgical procedures are beneficial. PMID- 3343868 TI - A shorter hospital stay after cardiac pacemaker implantation. AB - In an effort to shorten the hospital stay after implantation of a permanent cardiac pacemaker, some physicians have begun performing pacemaker implantation on an ambulatory basis. To assess the potential safety of shortening the duration of hospitalization after pacemaker implantation, we reviewed the complications that occurred in 100 consecutive patients after pacemaker implantation and noted the time after the implantation when the complications occurred. In our study group, all complications that necessitated invasive intervention occurred within 24 hours after the pacemaker implantation. Complications that necessitated noninvasive programming occurred as long as 72 hours after implantation, and all could have been safely corrected at the time of follow-up had the patient been dismissed at the 24-hour period. Although we do not believe that ambulatory pacemaker implantation should be routinely implemented at this time, the practice of dismissing patients at 24 hours after pacemaker implantation and scheduling subsequent outpatient follow-up seems to be safe and effective. PMID- 3343869 TI - Uterine leiomyosarcomas and benign smooth muscle tumors: usefulness of nuclear DNA patterns studied by flow cytometry. AB - Flow cytometry was used to determine the DNA ploidy pattern of paraffin-embedded archival tissue specimens from 90 surgically resected uterine smooth muscle tumors (49 leiomyosarcomas and 41 leiomyomas). The technique of Hedley was used for preparation of paraffin-embedded tissue into single dissociated nuclei, and the method of Vindelov was used for staining with propidium iodide. Among the 41 leiomyomas, most tumors (88%) had a DNA diploid pattern; the exceptions were two DNA tetraploid/polyploid and three DNA aneuploid samples. The DNA histograms of the 49 leiomyosarcomas (including 6 epithelioid leiomyosarcomas) were classified as follows: 9 cases (18%) exhibited a DNA diploid pattern, 29 cases (59%) had a DNA tetraploid/polyploid pattern, and 11 cases (23%) had DNA aneuploid peaks. Although DNA ploidy pattern cannot be used diagnostically to distinguish malignant from benign uterine smooth muscle tumors, the nuclear DNA ploidy pattern is an easily measured, objective determination that may have important prognostic significance for patients with uterine leiomyosarcomas. PMID- 3343870 TI - Blood conservation in cardiac operations. PMID- 3343871 TI - Ambulatory pacemaker procedures. PMID- 3343872 TI - Assessment of geriatric patients--spreading the word. PMID- 3343873 TI - Clinical diagnosis of immune inner-ear disease. AB - The purpose of this study was to develop a high-risk clinical profile of patients with autoimmune (immune-mediated) inner-ear disease. The records of 52 patients diagnosed over the past 5 years were reviewed. Age, sex, bilateral versus unilateral involvement, otologic symptoms, concomitant systemic immune disease, and presenting clinical diagnoses were recorded. The presenting diagnoses were Cogan's syndrome, Meniere's syndrome, Dandy's syndrome without hearing loss, or progressive sensorineural hearing loss without dizziness. Because Cogan's and Dandy's syndromes were relatively uncommon, the typical high-risk clinical profile was a middle-aged patient (often female) with bilateral, asymmetric, progressive sensorineural hearing loss, with or without dizziness, and occasional systemic immune disease such as rheumatoid arthritis. When a more common clinical diagnosis cannot be reached in suspicious patients, immune laboratory tests should be obtained and a trial of immunotherapy offered. Positive test results and beneficial response to therapy support a presumptive diagnosis of immune inner-ear disease. PMID- 3343874 TI - The management of congenital cholesteatoma: surgical results of 42 cases. AB - Radical surgery for congenital cholesteatoma leaves the patient, usually a child, with an ear that requires care for life. At the Otologic Medical Group, the intact canal wall technique has been used for many patients with cholesteatoma. To determine results of this management in the treatment of congenital cholesteatoma, we reviewed records of all patients treated between 1974 and 1985. Forty-two ears were studied in 41 patients. A closed middle-ear space was achieved in all cases, and an intact canal wall was maintained in 41 (98%). Follow-up averaged 4.3 years. Of the 41 cases with serviceable hearing before surgery, 28 (68%) had postoperative hearing within 10 dB of the best preoperative bone conduction threshold. Thirty-eight of the 41 achieved a final hearing result within 20 dB of the best bone conduction threshold. PMID- 3343875 TI - Hearing results and control of vertigo after retrolabyrinthine vestibular nerve section. AB - To determine the effect of retrolabyrinthine vestibular nerve section (RVNS) on hearing, vertigo, and associated symptoms, we reviewed our experience in 48 patients. Of the 48, 39 responded to a questionnaire. Although RVNS appeared to have little effect on hearing in Meniere's patients, 91% of non-Meniere's patients had significant and often delayed postoperative sensorineural hearing loss. Our results for vertigo control compared favorably to previous reports with 96% of Meniere's patients and 69% of non-Meniere's patients reporting improvement. Presently, we more frequently recommend RVNS as the primary procedure for the control of severe vertigo in Meniere's patients. Patients with vertigo from other causes must be carefully selected. PMID- 3343876 TI - Multichannel cochlear implantation: Utah-design. AB - The Utah-design multichannel cochlear implant consists of six intracochlear monopolar electrodes, one promontory electrode, and an indifferent electrode. Connection of the intracochlear system to the external sound processor is via a percutaneous pedestal system. Four of the intracochlear electrodes receive simultaneous stimulation. Twenty patients implanted at the University of Utah with more than 1 year of sound processor use were evaluated for the study. All patients wear their sound processors on a daily basis. Seven of the 20 are able to use the telephone without special devices. Nineteen patients were tested with open set CID sentences with an average 42.2% response. A comparison was made between live voice and taped voice open-set spondee word list performance, showing slightly better overall performance with live voice. PMID- 3343877 TI - Anterior epitympanic cholesteatoma with facial paralysis: a characteristic growth pattern. AB - Epitympanic cholesteatoma may involve the facial nerve at several anatomic locations resulting in functional impairment. The most common site of nerve compression is the middle-ear segment where the nerve is frequently devoid of bony covering. In five patients with facial palsy due to epitympanic cholesteatoma, a characteristic pattern of growth was recognized in which the cholesteatoma traversed the anterior epitympanum rather than taking the more common posterior route. Extension anteromedial to the head of the malleus leads to compression of the facial nerve in the region of the geniculate ganglion at the level of the middle cranial fossa floor. The most probable pathogenesis of this lesion is extension of disease along the embryologic course of either the saccus anticus or the anterior saccule of the saccus medius. Management of these lesions is surgical and may require, in addition to mastoidectomy with anterior and/or posterior atticotomy, middle fossa craniotomy and/or partial removal of the labyrinth for complete excision. PMID- 3343878 TI - Progression of hearing loss in bilateral Meniere's disease. AB - Otologists may be reluctant to perform labyrinthectomy in unilateral Meniere's disease, fearing the later development of bilateral disease and severe hearing loss in the previously normal ear. To illuminate this issue, we reviewed audiologic records for 85 patients diagnosed as having bilateral Meniere's disease at the University of Washington Hospital from 1969 to 1986. The progression of hearing loss in each ear was noted, as well as interaural relationships. Nine patients experienced a significant reversal, in which the initially better ear surpassed the other ear in hearing deficit, but only one of these patients could at any time have been considered a labyrinthectomy candidate, according to hypothetically liberal audiometric criteria. PMID- 3343879 TI - Ranulas--mucoceles of the oral cavity: experience in 26 children. AB - Ranulas or mucoceles of the floor of the mouth are uncommon but do occur in approximately 5% of patients undergoing submandibular duct relocation for the management of uncontrollable sialorrhea. Review of our experience with 26 patients over 12 years ending in 1986 substantiated a concept previously advocated by other authors that ranulas are usually extravasation pseudocysts developing after disruption of sublingual gland elements, and that excision of the ipsilateral sublingual gland is the management approach of choice. PMID- 3343880 TI - The role of adenoids in the development of normal speech following palate repair. AB - The controversy surrounding the various approaches to palate repair continues unabated. Issues which have been studied relative to the development of normal speech following palate repair have included surgical technique and the timing of surgery. However, regardless of the various refinements in surgery, a percentage of children require secondary surgery to resolve velopharyngeal insufficiency. To date, other factors which might be responsible for the development of normal speech have been ignored. The purpose of this report is to discuss the importance of the relative size of the adenoids in relation to the success or failure of primary palatoplasty. Velopharyngeal valving in noncleft (normal) children was also observed. Eight hundred fifty children with nonsyndromic clefts and 138 children with syndromic clefts were analyzed for speech results postpalatoplasty relative to adenoid size. One hundred normal children were also studied. The data suggest a strongly positive correlation between the incidence of hypernasal resonance postpalatoplasty and relative adenoid size in the cleft children. Velar adenoidal closure was consistently observed in both the cleft and normal children. PMID- 3343881 TI - Sigmoid sinus involvement in middle-ear infection. AB - It was thought that sigmoid sinus involvement from middle-ear infection would become a rare clinical entity with the introduction of antibiotics. However, this problem is still prevalent. Twelve hundred eighty cases of mastoid surgery were performed at Ghaem Medical Center and the author's private clinic between January 1978 and December 1985 in Mashad, Iran. In sixteen cases, surgically proven sigmoid sinus involvement was due to a bone eroding process of chronic ear infection. The pattern of the clinical picture is different than in the preantibiotic era. PMID- 3343882 TI - Alcohol and tobacco consumption in cancer of the mouth, pharynx, and larynx: a study of 316 female patients. AB - Three hundred sixteen female patients with cancer of the larynx, pharynx, and mouth were examined and the following cancer sites were compared with respect to alcohol and tobacco consumption: oropharynx, hypopharynx, larynx, epilarynx, lip, and mouth. The mean daily tobacco consumption of smokers and ex-smokers was not significantly different between cancer locations; however, significant differences between cancer sites were observed with regard to the proportion of nonsmokers. The percentage of nonsmokers was the highest for cancer of the lips and the lowest for cancer of the epilarynx. Cancer locations differed significantly depending on daily alcohol consumption. Consumption was the lowest for patients with cancer of the lips. The percentage of nondrinkers was high for cancers of the lips and larynx and low for cancer of the epilarynx. Examination of the nonsmoking/nondrinking females (27.2%) did not reveal any features specific to this group, except that the patients were older. PMID- 3343883 TI - Benign paroxysmal positional vertigo as a complication of postoperative bedrest. AB - Seven cases of benign paroxysmal positional vertigo (BPPV) after operation were reported, occurring between the fourth and 14th postoperative day. In three of the seven cases, the condition occurred when the patients first arose from bed after 5 to 6 days of postoperative bedrest. In two cases, BPPV occurred when patients moved their head while maintaining strict bedrest. In the other two cases, it occurred 1 to 4 days after patients had been released from bedrest. The cause of BPPV was considered to be postoperative bedrest which might have facilitated the deposition of precipitate on the cupula of the posterior semicircular canal. The prognosis was good, and all the patients recovered within 20 days. PMID- 3343884 TI - The nasolabial musculocutaneous flap: clinical and anatomical correlations. AB - The location of the facial artery beneath the facial mimetic muscles of the nasolabial groove allows surgical development of a true musculocutaneous flap. This report of 20 surgical flaps and six cadaveric dissections highlights the nasolabial musculocutaneous flap with its direct muscle perforating arteries which nourish the overlying skin. The absence of any flap's ischemic failure emphasizes the durability of the flap for various midface and oral reconstructive situations. Inferiorly-based flaps are preferable on the basis of discussed anatomical findings. The musculocutaneous flap is especially suited for circumferential interruption of cutaneous blood supply as in the "V-to-Y" and island pedicle flaps. PMID- 3343885 TI - Anesthesia management of microlaryngeal laser surgery in children: apneic technique anesthesia. AB - The purpose of this paper is to describe apneic technique general anesthesia which has been used in children for suspension microlaryngoscopy in the nontracheotomized patient. Apneic anesthesia uses a paralyzing drug in combination with controlled ventilation using halothane or isoflurane, nitrous oxide and oxygen, delivered through an endotracheal tube. Patients are monitored throughout the procedure with end-tidal CO2 levels and a cutaneous oximeter. Surgery is performed without the impediment of an endotracheal tube. This method, used in 240 patients ranging in age from 3 months to 18 years, eliminates the danger of a laser fire, gives an unobstructed view of the larynx, is safe, and is free of complications. All outpatients were discharged from the hospital within a few hours after the surgical procedure. PMID- 3343886 TI - Mandibular reconstruction in an irradiated field using median sternotomy and anterior rib axial graft. AB - Mandibular reconstruction in an irradiated field continues to be a challenge to the reconstructing surgeon. Several methods use rib grafts to bring vascularized tissue to the mandibular region. A median sternotomy provides excellent exposure to harvest the internal mammary artery and anterior axial rib graft for subsequent mandibular reconstruction. The modified technique described provides an alternative method of bringing a vascularized rib graft to an irradiated field for mandibular reconstruction avoiding multiple rib resections and microvascular anastomosis. This technique has been used in two patients who had anterior mandibular resection and irradiation therapy for advanced squamous cell carcinoma. The results from this technique were excellent and without major complications. PMID- 3343887 TI - Aluminum induced encephalopathy in the rat. AB - Aluminum tartrate (AlT) but not sodium tartrate (NaT) produces a progressive encephalopathy when injected intracerebroventricularly in the rat. This syndrome, lethal within 30-35 days, is characterized by progressively deranged behavior. An early startle reaction (day 14), later joined by locomotor discoordination (day 19) is followed by locomotor and electrocorticographic (ECoG) seizures (day 21) in chronically instrumented AlT rats. There is early dissociation between ECoG and locomotor aspects. When tested in the shuttlebox for estimation of learning and memory function 7-8 days after AlT injection, marked impairment of both active and passive avoidance was observed. Glucose uptake capacity of synaptosomes from brain areas of AlT and NaT animals was indexed by the 2-deoxy-D glucose method. Striatal and cortical synaptosomes showed reduced uptake activity 7 days following AlT injection. By day 14, hypothalamic areas also became affected, striatal uptake was further inhibited, and cortical uptake was reduced to 57% of control. The ECoG background rhythm remained unchanged until days 20 23, when the mean peak frequency was reduced. The model may be useful in the study of central aluminum toxicity and may have predictive validity in the testing of procedures to counter aluminum-associated encephalopathies in man. PMID- 3343888 TI - Zinc deficiency in the 11 day rat embryo: a scanning and transmission electron microscope study. AB - Zinc deficient rat embryos were obtained on the 11th day of pregnancy and examined by scanning and transmission electron microscopy. Scanning electron microscopy revealed an increase in the number of deformed embryos, as well as embryonic growth retardation. In addition, the epithelium of zinc deficient embryos displayed a marked increase in surface microvilli, as well as the presence of blebbing. Transmission electron microscopy indicated extensive cell death in the neural epithelium which was apparently more severely damaged by zinc deficiency than were mesenchymal cells. Mitochondrial cristae were affected to a greater degree than any other membrane of the cell and cristael disintigration appeared to represent the principal cellular lesion preceding necrosis of neural cells and neural tube teratology. PMID- 3343889 TI - Some characteristics of a high molecular weight lipid-protein aggregate and its possible role in intracellular fatty acid metabolism. AB - Several physical aspects of a high molecular weight lipid-protein aggregate separated by gel chromatography from chick and rat liver cytosol and its possible role in intracellular fatty acid metabolism were investigated. Electron microscopic examination of the high molecular weight lipid-protein aggregate indicated spherical particles with a diameter range of 200-600 A. This structure is consistent with a microemulsion particle of triglyceride encapsulated by phospholipid and protein. Uptake of fatty acids by microsomes occurred from the same lipid-protein aggregate, and the triglycerides synthesized in microsomes also became associated with these particles in the cytosol. The lipid-protein aggregate prepared by different homogenization methods showed identical ratios of components, but these ratios changed following incubation. These findings lend support to the concept that this aggregate plays a physiological role in intracellular lipid metabolism, and may be identifiable with previously reported subcellular fatty acid and triglyceride pools. PMID- 3343890 TI - A comparison of the central and peripheral antimuscarinic effects of atropine and methylatropine injected systemically and into the cerebral ventricles. AB - We compared the relative abilities of atropine sulfate and methylatropine, injected i.v. and into the cerebral ventricles (icv), to block pharmacological responses mediated through central and peripheral muscarinic receptors. The hypotensive response to i.v. injection of acetylcholine (peripheral muscarinic receptors) was inhibited 50% by i.v. injection of 14.3 nmol (5.5 micrograms)/kg methylatropine and 147.8n molar equivalents (50 micrograms)/kg atropine sulfate. A similar degree of inhibition followed icv injection of 49.4 nmol/kg methylatropine and 384.2 nmol equivalents/kg atropine sulfate, indicating significant leakage out of the ventricular space. The pressor response to icv injection of neostigmine (central muscarinic receptors) also was inhibited more effectively by icv methylatropine than by atropine sulfate. Methylatropine was not effective in blocking central muscarinic receptors when injected i.v. PMID- 3343891 TI - Pyrimidine nucleosides enhance the efficacy of inhibitors of pyrimidine biosynthesis in cultured hepatocellular carcinoma cells. AB - Inhibition of colony formation in cultured hepatocellular carcinoma cells of the rat was used to test the efficacy of inhibitors of de novo pyrimidine biosynthesis as potential anticancer drugs. N-(phosphonacetyl)-L-aspartic acid (PALA) (10 and 100 micrograms/ml) and 5-aza-5,6-dihydroorotic acid (DHOX) (100 micrograms/ml) inhibited the formation of colonies and these inhibitions were completely reversed by inclusion of 0.1 mM uridine, the end product of de novo pyrimidine biosynthesis, in the culture medium. With some lots of fetal bovine serum where PALA and DHOX had little effect on inhibiting colony formation, addition of 0.1 mM cytidine restored the inhibitory characteristics of PALA and, to some extent, DHOX. The results demonstrate that cytidine levels modulate the inhibitions of hepatoma colony formation by both PALA and DHOX and that co administration of these drugs together with cytidine provides a simple expedient to increase drug efficacy. PMID- 3343892 TI - Developmental pattern of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat. AB - The activity, protein concentration and catalytic efficiency of hepatic 3-hydroxy 3-methylglutaryl coenzyme A reductase was determined in rats aged 1 to 199 days. Microsomal enzyme total activity peaked on day 24, during weaning, and again on day 63, during the onset of puberty. Increased enzyme activity during weaning resulted primarily from an increase in the catalytic efficiency of the enzyme with a slight reduction in enzyme protein content. The rise in enzyme activity during the onset of puberty, however, was primarily the result of an increase in enzyme protein concentration. Thus, the activity of reductase in mammalian livers reflects, at different stages in development, the modulating influence of both the total number of reductase molecules and the catalytic efficiency of the enzyme. PMID- 3343895 TI - GTP effects in rat brain slices support the non-interconvertability of M1 and M2 muscarinic acetylcholine receptors. AB - GTP (guanosine-5'-triphosphate) markedly reduced high-affinity 3H-oxotremorine-M binding to M2 receptors on brain slices in autoradiographic experiments while 3H pirenzepine binding to M1 receptors was largely unaffected. The distribution of M1 receptors so labelled was also not altered by GTP to include former M2-rich regions, thus indicating that GTP could not, by itself, interconvert high agonist affinity M2 receptors to M1 receptors. PMID- 3343893 TI - Effects of estrogens and progesterone on the catecholaminergic activity of the adrenal medulla in female rats. AB - Some reports in the literature allow to suspect the existence of an effect of sexual steroids on the adrenal catecholamines. To test this possibility, we have examined the catecholaminergic activity in the adrenal medulla of normal cycling rats in three phases of estrous cycle and of ovariectomized (OVX) rats injected with pharmacological doses of estradiol (ES), 2-hydroxyestradiol (HE) and/or progesterone (P). Adrenomedullary content of norepinephrine (NE) was similar during the estrous cycle, while epinephrine (E) content was increased during diestrous. This increase was concomitant with an increased phenylethanolamine-N methyltransferase (PNMT) activity. Moreover, the monoamine oxidase (MAO) activity was significantly increased during proestrous, while the catechol-O methyltransferase (COMT) activity was significantly decreased during estrous. In addition to these observations, ovariectomy caused a significant reduction of the E/NE ratio and of COMT and MAO activities. Administration of ES to OVX rats increased the E content, the E/NE ratio and the COMT activity as compared to vehicle-treated OVX rats. Administration of P to OVX animals led also to a significant increase of the E/NE ratio and of the COMT activity but not of the E content, while the administration of this steroid to OVX rats previously treated with ES only increased the COMT activity. Finally, administration of HE caused non-significant changes in NE and E contents and in MAO, COMT and PNMT activities. We can conclude that sexual steroids seem to be able to modify the catecholamine metabolism in the adrenal medulla and, hence, they could alter the ability of this gland to store and release these amines. PMID- 3343894 TI - Diabetic state-induced modifications of succinylcholine binding mode in the microsomal fractions of mouse skeletal muscles. AB - The skeletal muscles of alloxan-induced diabetic mice and genetically diabetic KK CAY mice are hypersensitive to a depolarizing blocker, succinylcholine (SuCh) but not to the competitive antagonist, d-tubocurarine (d-TC). The mechanism by which the action of the depolarizing blocker is modified in the diabetic state was investigated on the binding of 14C-SuCh to the microsomal fraction isolated from mouse skeletal muscles. The Scatchard plot of microsomal preparations from normal ddY mice showed positive cooperativity in SuCh binding, whereas that of the preparations from alloxan-induced diabetic mice as well as genetically diabetic KK-CAY mice lost the positive cooperative interactions. The dissociation constant (Kd) of high affinity site in diabetic muscles was significantly lower than that in non-diabetic ddY muscle. The microsomal fractions from denervated muscles of normal ddY mice maintained weakly positive cooperativity in SuCh binding, and the affinity of SuCh binding in denervated muscles was lower than that of non denervated muscles. In conclusion, the diabetic state selectively altered the SuCh binding mode. This alteration seems to be closely correlated with the pharmacological hypersensitivity to SuCh. PMID- 3343896 TI - The influence of histamine on precursors of granulocytic leukocytes in murine bone marrow. AB - The effect of histamine on granulocytic progenitor cells in murine bone marrow was studied in vitro. When bone marrow cells were cultured for three days with the drug, 10(-8) M to 10(-5) M of histamine stimulated differentiation and proliferation of myeloid precursor cells. Subsequently, the number of descendant cells, such as metamyelocytes and neutrophils, increased dose-dependently. Co existence of equimolar H2 blockers such as cimetidine and ranitidine completely suppressed this effect of histamine, though this was not the case with an H1 blocker/histamine combination. Significant increase in 3H-thymidine incorporation was observed almost exclusively in myeloblasts, promyelocytes and myelocytes after exposure to histamine at concentrations higher than 10(-8) M. Also, selective incorporation of 3H-histamine into bone marrow cells was observed in myeloblasts and promyelocytes, but histamine incorporation was not influenced by the presence of either of histamine agonists or antagonists. While histamine, via H2 receptors, selectively increased the number of granulocytic colony forming units in culture (CFU-C), it had no such effect on macrophage colonies. Considering these findings, it was concluded that histamine promotes proliferation and differentiation of granulocytic myeloid cells via 1) H2 receptors in the CFU-C stage and 2) histamine receptors which are neither H1 nor H2 in the stages of myeloblast and promyelocyte differentiation. PMID- 3343897 TI - Society for Magnetic Resonance Imaging. Sixth annual meeting, 27 February-2 March, 1988, Boston, Massachusetts. Program and abstracts. PMID- 3343898 TI - [Radiotherapy in the combined modality treatment of patients with malignant tumors]. AB - Proceeding from an analysis of their own experience in the combined treatment of over 4000 patients with malignant tumors of the main sites, the authors evaluate the importance of the methodological aspects of pre- and post-operative radiation therapy: levels of total absorbed doses, techniques of their fractionation, object and volume to be irradiated, and values of an interval between modalities of combined therapy. Their improvement on the basis of the latest advances in oncology, clinical radiology and radiobiology is one of the realistic ways for improving therapeutic results. The prospects of such improvement are associated with the development of uncommon dose fractionation schemes and the use of various modifiers in preoperative irradiation and extended indications for post operative irradiation. PMID- 3343899 TI - [Course of lymphogranulomatosis with primary location below the diaphragm]. AB - Some peculiarities in a course of stage I-II Hodgkin's disease with a primary site below the diaphragm are analyzed. This site is more common in men and in a mixed cell histological variant of lymphogranuloma. The frequency of recurrence is higher in this group than in patients with a primary site above the diaphragm. Recurrences affect more frequently the lymphatic areas above the diaphragm. The data obtained suggest the necessity of irradiation of the lymphatic collectors on both sides of the diaphragm in a primary site below the diaphragm, particularly in patients with "mixed cell" and "lymphoid depletion" histological variants of lymphogranuloma. PMID- 3343901 TI - [A mathematical model for describing radiation complications]. AB - The paper is devoted to the development of a mathematical model for describing probabilities of occurrence of radiation complications on the skin (as well as in other normal organs and tissues) during its irradiation with homogeneous and inhomogeneous dose fields as a function of an irradiated skin area. The model naturally necessitates the isolation of an equivalent dose (an equidosimetric value) introduced by I. B. Keirim-Marcus which can be effectively used for comparison of homogeneous and inhomogeneous dose fields in normal organs and tissues. The development of mathematical models describing probabilities of occurrence of radiation complications in normal organs and tissues opens up new opportunities for improvement of methods of cancer radiotherapy design. PMID- 3343902 TI - [Basic trends in the reconstruction of the system of postgraduate training of radiotherapists]. AB - The authors have summed up the experience accumulated over 20 years at the Chair of Clinical Radiology of the Central Order of Lenin Institute of Advanced Medical Training. Doctors majoring in this field, usually become radiologists at the age over 35 when their creative initiative is on a decrease. Therefore the authors have proposed numerous measures aimed at the improvement of the system of training in radiology and an increase in the number of young specialists. PMID- 3343900 TI - [Radiation injuries of the vertebrae]. AB - The results of examination of 12 patients with vertebral radiation injuries were analyzed. The authors considered clinical and x-ray signs of radiation osteoporosis (5), radiation osteonecrosis (7 patients), and complications in the form of pathological fractures of vertebral bodies. Vertebral radiation injuries were most frequently detected 6-12 yrs. after the discontinuation of radiotherapy. PMID- 3343904 TI - [Immuno-scanning of human colon cancer xenografts using a labeled monoclonal antibody to the carcinoembryonic antigen]. AB - The results of experiments using 131I-labelled monoclonal antibody (131I-MoAb) were described. The experiments were staged on nude male mice with transplanted human colon adenocarcinoma of the 34th generation (RTK-12). Tumor sizes by the time of 131I-MoAb administration varied from 1 to 3 cm. 131I-MoAb specific radioactivity was 456.6 kBq/micrograms in the volume of 0.3 ml. The same amount of 131I-Na was administered to control animals. Scanning on the Scintimat-2F (Siemens) was performed 1, 2, 3 and 4 days after injection of 131I-MoAb. Three days before scanning 0.2% KI was added to the drinking water. Some animals were decapitated on the 2nd-3rd day for radiometry of organs and tissues. After the injection of 131I-MoAb 10-fold less than the CEA serum concentration and with specific radioactivity of 370-444 kBq its tumor accumulation in 48 h was 10-15 fold higher than that in the surrounding tissues resulting in better tumor scans. Intensive dehalogenation of 131I-MoAb in vivo and related 131I accumulation in the thyroid and adrenal glands (in the medullary layer) required the administration of stable iodine not only before but also after injection of the radioactive agent. PMID- 3343903 TI - [Scintigraphic evaluation of the results of treatment of alcoholic liver cirrhosis]. AB - The results of static and dynamic scintigraphy in patients with alcoholic liver cirrhosis showed changes in liver sizes, a decrease in the RL/LL ratio, an increase in spleen sizes, the reduction or distortion of the L/S ratio, extrahepatic uptake of RP, and predominance of the arterial component of the blood flow over the portal one. However the main scintigraphic signs of alcoholic liver cirrhosis were undetectable. After therapy (lymphovenous anastomosis, embolization of the hepatic artery) the recovery of functions was more rapid in patients with cirrhosis of alcoholic etiology who discontinued alcohol consumption than in those with cirrhosis of some other etiology. PMID- 3343905 TI - [Analysis of errors in the determination of the collective equivalent dose in x ray diagnostic studies]. AB - The paper is devoted to an analysis of random errors in the determination of a collective effective equivalent dose resulting from radiodiagnostic investigations. The error of a collective dose does not exceed 30% and hardly depends on dose errors in human organs and tissues. The authors have established an extent of overestimation of the risk of long-term radiation effects in patients after x-ray investigations. PMID- 3343906 TI - [Perfusion scintigraphy in pulmonary dystrophy]. PMID- 3343907 TI - [Circadian rhythm of the level of metronidazole in transplantable tumors and tissues of animals]. PMID- 3343908 TI - [An approach to establishing procedural regulations for x-ray studies]. PMID- 3343909 TI - [Principles of regulating the irradiation of patients in x-ray diagnosis]. PMID- 3343910 TI - [Principles of radiation dose limitation and standardization in x-ray diagnosis]. PMID- 3343911 TI - Metabolic, thermoregulatory, and psychophysiological responses during arm and leg exercise. AB - The present investigation compares metabolic, thermoregulatory, and psychophysiological responses during upper and lower body exercise in different environmental conditions. Eight males performed four, 60-min exercise bouts using either arm or leg ergometry in ambient temperatures of 23 degrees C (relative humidity = 75%) and 33 degrees C (relative humidity = 57%). Power output was 75 W for all experiments. Oxygen consumption, rectal and skin temperatures, heart rate (HR), and rating of perceived exertion were measured during exercise. Exercise oxygen consumption averaged 1.54 l.min-1 across all experiments and was equivalent to 60% of arm and 37% of leg peak values. Rectal temperature increased (P less than 0.001) an average of 0.43 degrees C and did not differ due to experimental conditions. Exercise performed in the heat resulted in higher skin temperature (P less than 0.001), regardless of whether the arms or legs were used. HR and rating of perceived exertion were greater (P less than 0.001) in arm (132.9 b.min-1, 14.4 units) than leg (108.9 b.min-1, 10.9 units) experiments. When arm exercise was performed in the heat, HR was 6 b.min-1 greater than when performed in the cool. Greater relative exercise intensity in arm work resulted in higher HR and rating of perceived exertion at the given power output. Similar rectal temperature increases in all experiments indicate that core temperature is controlled by absolute heat production, regardless of mode of exercise and ambient temperature. PMID- 3343912 TI - Reliability and concurrent validity for a 7-d re-call of physical activity in college students. AB - We conducted four studies to examine the reliability and validity of a 7-d re call for estimating free-living physical activity in college students. High and reproducible correlations (r's = 0.82 to 0.87) between the re-call and a concurrent 7-d diary were observed, and re-call effectively classified subjects into highly active (greater than or equal to 280 kcal.kg-1.wk-1) and inactive (less than 245 kcal.kg-1.wk-1) groups. Significant correlations between re-call and a psychometric predictor of physical activity (self-motivation) were also robust across samples and consistent with those seen when direct measures of activity have been used. Increases in time and distance records for supervised running were accompanied by increases in total and vigorous re-call, but not in moderate re-call, supporting the re-call's sensitivity to measured changes in group activity levels. Re-call was not, however, highly correlated with supervised running, and this is consistent with its use as a measure of free living activity. Re-call was also not spuriously contaminated by response distortion or attitudinal variables, and intra-class reliability for repeated assessments of total (PI = 0.89) and vigorous (PI = 0.90) re-call was high across 7 wk. Finally, re-call provided a better estimate of a 7-d diary than did practical bio-behavioral estimates of habitual activity (12-min run and skinfold thickness), and re-call was highly correlated with a concurrent physical activity questionnaire (r's = 0.83 to 0.94) and VO2max (ml.kg-1.min-1) (r = 0.61). Our results are consistent with previous studies on community-based adult populations; they support that the 7-d re-call is reliable and valid for college students when compared with concurrent bio-behavioral and self-report estimates of physical activity. PMID- 3343913 TI - Effects of electrolyte and nutrient solutions on performance and metabolic balance. AB - Three commercial sport drinks, solutions of their individual minerals and glucose, and water were used to maintain water balances in six men during 4 h of physical activity in a 35 degrees C room. Each solution was provided for 5 consecutive days to each man during the 12-wk study. Complete mineral and water balances (including sweat losses) were conducted. Oxygen consumption and carbon dioxide production were measured during two levels of sub-maximal and during a maximal treadmill performance test. All of the solutions, including water, were equally effective in maintaining water and mineral balances, and moderate physical performance while the men were consuming an adequate all liquid diet. All of the solutions containing carbohydrates increased respiratory exchange ratios. These increases were significant during maximal performance for only two of the commercial products. These two products also produced the higher values for most of the performance evaluations, although they were not generally significantly different from values obtained while other solutions or water were consumed. The major benefit of these commercial sport drinks are their prevention of hypohydration due to an increase in voluntary fluid intakes. PMID- 3343914 TI - Exercise capacity and nitrogen loss during a high or low carbohydrate diet. AB - Twelve obese women completed a maximal and an endurance exercise test (70% peak VO2) during a weight maintenance week. For the next 4 wk, the women consumed either a high (71%) carbohydrate (HC) or a low (33%) carbohydrate (LC), isonitrogenous very-low-calorie diet (VLCD) of 2,219 kJ (530 kcal).d-1. A supervised exercise session at 60% peak VO2 took place 3 times.wk-1 for 30 to 45 min. Peak VO2 and exercise endurance tests were repeated during the fourth week of the VLCD. One week of a 4,186 kJ (1000 kcal) diet followed the VLCD. The average weekly weight loss was 1.7 +/- 0.1 kg for the HC group and 2.0 +/- 0.2 kg for the LC group. Urinary nitrogen loss was greater for the LC group early in the VLCD but not different than HC over the entire experimental period. Serum cholesterol and high-density lipoprotein-cholesterol decreased in both groups but the ratio of these lipids improved over the treatment. Serum beta-hydroxybutyrate and uric acid increased significantly more for the LC than the HC group. Although absolute peak VO2 decreased, VO2 relative to body weight was maintained. Time to exhaustion improved by 36% for both groups in the endurance exercise tests. The endurance exercise R ratio was significantly more depressed by the LC than the HC treatment. In summary, both supervised treatments were effective in causing substantial weight reduction and improved blood lipid profiles in healthy young women but caused a net loss of body protein. Neither treatment compromised ability to participate in a thrice weekly exercise program. Although peak aerobic capacity did not increase, aerobic endurance at a fixed sub-maximal exercise load was improved. PMID- 3343916 TI - Effects of low- and high-repetition resistive training on lipoprotein-lipid profiles. AB - Thirty-seven healthy untrained males (age = 21 +/- 1 yr; range = 19 to 35 yr) were studied to determine the effects of 10 wk of low- and high-repetition resistive training on lipoprotein-lipid profiles. Subjects were assigned to 1 of 3 groups: a low-repetition group (N = 15) that trained using 4 to 6 repetitions maximum or a high-repetition group (N = 14) that used 14 to 16 repetitions maximum in their training or to an inactive control group (N = 8). The number of sets was adjusted to equalize workloads. Muscular strength increased significantly in both training groups as indicated by the increase in the one repetition maximum test (P less than 0.05). VO2max, body weight, and percent body fat did not change in either of these groups. However, fat-free weight increased significantly in both training groups (both P less than 0.05). The low-repetition training program resulted in no significant changes in the plasma concentrations of triglycerides (104 +/- 15 vs 89 +/- 8), total cholesterol (150 +/- 7 vs 141 +/ 6), high-density lipoprotein (HDL)-cholesterol (40 +/- 1 vs 41 +/- 2), and HDL2 cholesterol (7 +/- 1 vs 7 +/- 1). A similar pattern was observed for the high repetition group ([i.e., no significant changes in the concentrations of triglycerides (87 +/- 10 vs 89 +/- 8), total cholesterol (148 +/- 6 vs 162 +/- 6), HDL-cholesterol (40 +/-2 vs 40 +/- 2), and HDL2-cholesterol (6 +/- vs 1 vs 7 +/- 2)]. All lipid values were expressed in milligrams per deciliter (mean +/- SE).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343915 TI - Meal-induced thermogenesis following exercise training in the rat. AB - The effects of treadmill exercise on the thermic effect of a meal were studied in male Sprague-Dawley rats (370 to 400 g, 4 to 5 months of age). Rats were exercised for 60 min, 5 d.wk-1 for 8 to 10 wk, at a speed of 27 m.min-1 and with a grade of 8%. Sedentary (N = 9) and exercised (N = 8) rats were given food and water ad libitum. Oxygen consumption was measured at rest and following the ingestion of a meal consisting of 81% carbohydrate, 9% protein, and 10% fat (by calories). In those animals that were exercised, oxygen consumption measurements were performed 24 h after the completion of an exercise bout. Although all animals gained weight during the experimental period, the exercised group gained significantly less than did the sedentary rats. Resting oxygen consumption [ml/(min X g body mass.67)] was not significantly different between the exercised and sedentary rats. The ingestion of the high carbohydrate meal significantly increased mass-independent oxygen consumption above resting values in both groups; the values for the exercised rats were greater than those for the sedentary rats. However, there were no differences between the exercised and sedentary rats in meal-induced oxygen consumption when the data were expressed as a function of lean body mass [ml/(min X g lean body mass)] or as mass-independent lean body mass [ml/(min X g lean body mass.67)]. These data suggest that exercise trained rats have increased diet-induced thermogenesis and may be one factor in the loss of weight sometimes found in response to exercise. PMID- 3343917 TI - Differential effects of exercise intensity on serum uric acid concentration. AB - To investigate the effects of exercise intensity and short-term training on alterations in plasma uric acid, two series of experiments were performed using untrained male subjects. In series 1, 6 subjects (age 19 to 23 yr) cycled at 120% VO2max for 1 min followed by 4 min recovery until fatigue or until 24 repetitions had been completed. In series 2, 7 subjects (age 19 to 25 yr) cycled continuously at 65% VO2max for 2 h. In both experiments, short-term training was performed by repeating the exercise protocol for three consecutive days. In series 1, a progressive increase of 40% (P less than 0.05) was observed on day 1 in plasma uric acid concentration over the duration of the exercise. On day 2, pre-exercise values remained elevated over day 1 (mean +/- SD, 476 +/- 77 vs 352 +/- 30 mumol.l-1) and showed a further 23% increase (P less than 0.05) with exercise. Although resting uric acid concentrations on day 3 were elevated (P less than 0.05) over day 1, the exercise levels between day 1 and day 3 were not different (P greater than 0.05). In contrast, in series 2, prolonged sub-maximal exercise failed to stimulate increases in uric acid concentration either between days or within days. It is concluded that exercise intensity rather than total work output is a critical factor mediating increases in blood uric acid concentration. These results are consistent with the interpretation that uric acid formation may arise from purine nucleotide degradation and fast-twitch fiber utilization during conditions of high energy utilization. PMID- 3343918 TI - Physical fitness does not reflect physical activity patterns in middle-aged workers. AB - Questionnaires and a sub-maximal exercise test were used to assess occupational and leisure time physical activity as well as physical fitness in a standardized prospective study in 2,565 Belgian and Slovakian middle-aged healthy workers. Less than 5% of the subjects engaged in strenuous work requiring an energy expenditure above 31.5 kJ.min-1. One-third of the Belgians and 50% of the Slovakians reported no heavy leisure time activity during the preceding 12 months. Physical fitness, defined as the workload at heart rate 150 beats.min-1 (standardized for body weight), was significantly higher in Slovakians as compared to Belgians (1.52 +/- 0.28 W.kg-1 and 1.48 +/- 0.28 W.kg-1; P less than 0.001). Occupational physical activity in Belgians and heavy leisure time activity in Slovakians were independently related to fitness levels. However, each activity score explained less than 1% of the variance of physical fitness. We conclude that in these mainly sedentary, middle-aged subjects, fitness levels are independent from the usual physical activity patterns. PMID- 3343919 TI - Reproductive hormonal profiles of endurance-trained and untrained males. AB - This study compares the resting reproductive hormonal profiles of untrained (N = 11) and endurance-trained (N = 11) males. Testosterone, free testosterone, estradiol, luteinizing hormone (LH), prolactin, and cortisol were measured by radioimmunoassay in resting blood samples (8 h fast) collected every 60 min for 4 h. The endurance-trained group had been active for (mean +/- SE) 12.4 +/- 6.7 yr, 6.6 +/- 0.2 d.wk-1, 68.5 +/- 4.4 min.d-1, while the untrained group was sedentary. Neither group had histories of hypothalamic-pituitary-testicular disorders. The overall 4 h mean testosterone and free testosterone levels were significantly (P less than 0.05) lower in the trained group (4.99 +/- 0.46 vs 7.25 +/- 0.67 ng.ml-1, and 17.2 +/- 1.4 vs 23.6 +/- 0.6 pg.ml-1, for the trained and untrained groups, respectively). The LH of the endurance-trained group was higher (15.3 +/- 1.9 vs 11.7 +/- 1.2 mIU.ml-1, P = 0.06); however, LH pulse frequency and amplitude did not differ between groups. An enhanced estradiol feedback to the hypothalamus-pituitary could not account for the elevated LH, as estradiol levels were similar in the groups. Prolactin and cortisol levels were normal and did not differ between groups. The results suggested normal hypothalamic-pituitary function existed in the trained subjects, and prolactin and cortisol were not causative factors in the lowered resting testosterone and free testosterone levels. The findings indicate that chronic endurance training lowers testosterone and free testosterone in males possibly by impairing testicular function. PMID- 3343921 TI - Effects of fatigue on activation profiles and relative torque contribution of elbow flexor synergists. AB - The purpose of this study was to examine changes in elbow flexion synergies as a result of fatigue. Subjects performed a series of five isometric contractions at 10% maximum voluntary contraction step intervals. Pre- and post-fatigue surface electromyograms for the muscles were rectified, integrated, normalized, a representative equation determined using the least-squares method, and the equations numerically differentiated. The differentiated curves represent the change of excitation (and therefore, change of isometric torque) with respect to the change in resultant torque (dIEMG/dT). Pre-fatigue synergy, as indicated by the dIEMG/dT, was characterized by both co-activation and trade-off patterns. The nature of the synergy was changed as a result of fatigue. This technique, focusing upon synergistic patterns, quantifies differences in excitation profiles in a manner not previously described. PMID- 3343920 TI - Hydrostatic weighing without head submersion: description of a method. AB - Hydrostatic weighing (HW) was performed at residual volume (RV) and total lung capacity without head submersion (TLCNS). Ninety-five males (25.6 +/- 4.9 yr) and 87 females (22.6 +/- 5.2 yr) were studied at two laboratory sites using identical protocols. Twenty males and 20 females were separated from the original group and randomly assigned to cross-validation groups. RVs were determined by the oxygen dilution method. Vital capacity was determined with the subject submerged in water to the shoulders. Underwater weight was determined using 10 trials at RV and 5 trials at TLCNS, with the order of methods randomly assigned. Regression analysis provided an equation to predict body density (pDb) at RV from body density (Db) at TLCNS. The equation for males was pDb (HW at RV) = 0.5829 (DbHW at TLCNS) + 0.4059, r = 0.88, SEE = 0.0067. The equation for females was pDb (HW at RV) = 0.4745 (DbHW at TLCNS) + 0.5173, r = 0.85, SEE = 0.0061. Cross validation showed no significant differences using Db from HW at RV (males = 1.0626 g.ml-1, females = 1.0493 g.ml-1 and pDb from HW at TLCNS (males = 1.0625 g.ml-1, females = 1.0479 g.ml-1). The correlation coefficient SEE and total error for males were r = 0.95, 0.0043, and 0.0041, respectively and for females r = 0.82, 0.0084, and 0.0085, respectively. Mean percent fat for RV and TLCNS was identical for males and differed by 0.7% for females. Test-re-test data indicated the TLCNS procedure was reliable (r = 0.98).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343922 TI - Training effects of sub-maximal electrostimulation in a human muscle. AB - This paper compares the effects of 6 wk of sub-maximal training by electrostimulation (100 Hz) and voluntary contractions on the contractile properties of the adductor pollicis muscle in intact man. The daily training program consisted of ten series of twenty 1-s isotonic contractions (60 to 65% of maximum) separated by 1-s intervals. The observed increase in muscle force, tested in maximal voluntary and electrically evoked contractions, appears to be significantly smaller during electrostimulation than during a training session performed by voluntary contractions. The increase in force recorded during electrostimulation is not associated with changes in the tetanus rates of tension development and tension relaxation (dP0/dt). Conversely, the tetanus time course is found to be significantly accelerated in muscles trained by voluntary contractions. No change of the surface action potential total area was observed during both training procedures. Furthermore, electrostimulation does not improve muscle resistance to fatigue, which is observed to be significantly increased after training by voluntary contractions. This study indicates that electrostimulation augments the muscle force of contraction by changing peripheral processes associated with intra-cellular events, without modifying the nervous command of the contraction. The comparison of the peripheral changes recorded during sub-maximal training by electrostimulation and voluntary contractions suggests that electrostimulation is less efficient, but complementary to voluntary training because the number and the type of trained motor units are different in the two procedures. PMID- 3343923 TI - Differential respite needs of aging parents of individuals with mental retardation. PMID- 3343924 TI - Discovering the community living arrangements--neighborhood equation. PMID- 3343925 TI - Special sitters: youth as respite care providers. PMID- 3343926 TI - Multiple-behavior comparison of group and individual instruction of persons with mental retardation. PMID- 3343927 TI - Personal support networks--benefits and liabilities. PMID- 3343928 TI - A parent's response to "are we professionalizing parents"? PMID- 3343929 TI - Individuals with mental retardation and the criminal justice system: the view from states' attorneys general. PMID- 3343930 TI - Relationship between trabecular vertebral body density and fractures: a quantitative definition of spinal osteoporosis. AB - To evaluate the relationship between vertebral fractures and trabecular vertebral body density (TVBD), as measured by computed tomography (CT), we evaluated 110 female and 38 male patients referred consecutively to our clinic for an osteoporosis evaluation. Number of fractures per patient and TVBD was negatively correlated in both males and females (r = -.64, P less than .001 and r = -.69, P less than .001, respectively). Based on this relationship and that between percent of patients with fracture and TVBD, we devised four different approaches to calculate the fracture threshold. (1) Because the x-axis intercept of this regression line represents the TVBD value at zero fractures, this intercept can be considered the fracture threshold, which was 103 mg/cm3 for females and 132 mg/cm3 for males. (2) Breakpoint analysis of the relationship between the number of vertebral fractures per patient v TVBD gave a fracture threshold value of 98 mg/cm3 for females, but for males we were unable to compute a threshold value because of the small sample size. The percentage of patients with fractures was also negatively correlated with TVBD for males and females (r = -.98, P less than .001, and r = -.94, P less than .001, respectively). (3) the x-axis intercept of this relationship, which represents the fracture threshold, was 123 mg/cm3 for males and 101 mg/cm3 for females. (4) The fracture threshold, calculated as the mean TVBD + 2 SD for patients with fracture(s), was 120 and 92 mg/cm3 for males and females, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3343931 TI - Independent effects of liver disease and chronic alcoholism on thyroid function and size: the possibility of a toxic effect of alcohol on the thyroid gland. AB - In an autopsy study we found thyroid volume significantly decreased in alcoholics with liver cirrhosis as compared to matched controls: 15 mL (range, 7 to 37 mL) v 25 mL (range, 13 to 90 mL) (P less than .01). At the same time the amount of fibrosis of the thyroid glands was higher in the alcoholics as compared to the matched controls: 20% (range, 6% to 40%) v 12% (range, 6% to 23%) (P less than .01). In order to evaluate the relative importance of alcohol consumption and liver disease on thyroid function and ultrasonically determined size, three groups of patients and matched controls (sex, age, weight, and smoking habits) were investigated: group 1, 18 patients with nonalcoholic liver cirrhosis; group 2, 21 consecutive chronic alcoholics (greater than 100 g of alcohol daily for greater than 5 years) without liver cirrhosis (all had biopsy proven fatty change or normal liver); group 3, 31 nonalcoholic patients with chronic nonhepatic, nonrenal disease. In group 1 median thyroid volume and serum FT4I, FT3I, and TSH levels were unchanged compared with the controls. In group 2 median thyroid volume was 13 mL (range, 9 to 32 mL) compared with 27 mL (range, 12 to 44 mL) in the controls (P less than .005). Serum T3 and FT3I levels were reduced, while T4, FT4I, and TSH levels were unaltered. In group 3 serum T3 and FT3I levels were reduced while serum FT4I and TSH levels and thyroid volume were unaltered compared with the controls. It is suggested that alcohol may have a toxic effect on the thyroid gland independent of the degree of liver damage. PMID- 3343932 TI - Relationship between neonatal birth weight and maternal plasma amino acid profiles in lean and obese nondiabetic women and in type I diabetic pregnant women. AB - Profiles of hemoglobin A1c (HbA1c) and concentrations of plasma glucose and 18 plasma amino acids were obtained in ten nonobese, insulin-dependent type I diabetic women, in 9 age- and weight-matched normal women and in ten obese nondiabetic women throughout pregnancy and postpartum. In late gestation, the period of maximum fetal growth, average HbA1c, plasma glucose, and total amino acid concentrations in diabetic mothers were significantly elevated above lean control values. No differences existed between the obese and lean control groups. Lean diabetic mothers also had significantly heavier babies (mean +/- SEM) relative to the 50th percentile for gestational age and sex (119 +/- 9%) than did the lean control group (94 +/- 3%, P less than .05). Relative birth weights among control lean and obese mothers did not differ significantly (94 +/- 3% v 104 +/- 5%). Late pregnancy profiles of HbA1c and average plasma glucose did not correlate with relative weight of neonates whereas average total plasma amino acids and six individual amino acids did correlate with this parameter. These data suggest that maternal plasma amino acid concentrations may influence fetal weight generally and may have an important role in the development of fetal macrosomia in diabetic pregnancies. PMID- 3343933 TI - Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in normal adults. AB - Aspartame (APM) is a dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of the product might elevate plasma aspartate and phenylalanine concentrations. Eight normal adults (four male, four female) ingested three successive 12-oz servings of APM-sweetened beverage at two-hour intervals. The study was carried out in two parts in a randomized cross-over design. In one study the beverage was not sweetened. In the other, the beverage provided 10 mg APM/kg body weight per serving. Plasma amino acid concentrations were measured throughout the six-hour study period. The addition of APM to the beverage had no significant effect on plasma aspartate concentration. APM addition did increase plasma phenylalanine levels 1.64 to 2.05 mumol/dL above baseline values (5.09 +/- 0.82 mumol/dL) 30 to 45 minutes after each dose. However, plasma phenylalanine levels did not exceed normal postprandial values at any time. The data indicate ready metabolism of APM's amino acid content when administered at levels likely to be ingested by individuals who are heavy users of such beverages. PMID- 3343935 TI - Pleural protein concentration and liquid volume in spontaneously hypertensive rats. AB - To determine the effect of systemic vascular hypertension on fluid balance in the pleural space, we studied the spontaneously hypertensive rat (SHR) and its genetic normotensive control, the Wistar-Kyoto rat (WKY). We measured arterial and venous pressures, total protein and albumin concentrations of pleural liquid and plasma, pleural space thickness, and pleural surface pressure in SHR and WKY that were matched for weight (260-300 g). Protein concentration was measured by a manual Biuret test and albumin concentration was measured by the bromcresol green colorimetric method. Pleural liquid thickness was measured in situ using light microscopy. Pleural surface pressure was assumed to equal pleural liquid pressure. In the SHR, total protein and albumin concentrations in pleural liquid were lower than in WKY, and pleural space thickness was larger in SHR than in WKY. These results are consistent with a higher capillary pressure and greater fluid filtration in SHR. PMID- 3343934 TI - The effects of steroidal and nonsteroidal anti-inflammatory agents on uptake of Evans blue in experimental metastasis. AB - The effects of anti-inflammatory drugs on uptake of Evans blue were studied in solitary Walker carcinosarcomas implanted in the livers of Sprague-Dawley rats. Animals were sacrificed at 5 min, 30 min, and 6 hr after administration of the anti-inflammatory drugs and Evans blue, and spectrophotometric measurements of the Evans blue in tumor and normal liver tissue were carried out. Uptake of Evans blue in the tumors was significantly decreased at all time periods after the injection of the following, as compared to controls: steroids (cortisol, methylprednisolone, and triamcinolone), the antihistamine diphenhydramine, and nonsteroidal anti-inflammatory agents (naproxen, ibuprofen, indomethacin, and phenylbutazone). The effects of these drugs on uptake of Evans blue in the normal liver were more variable. PMID- 3343936 TI - Interaction of plasma colloid osmotic pressure and joint fluid pressure across the endothelium-synovium layer: significance of extravascular resistance. AB - Fluid exchanges between blood and a synovial joint cavity across two membranes in series--synovial capillary wall (fenestrated) and synovial intima (modified connective tissue). The relation between transsynovial absorption of intraarticular Krebs solution (flow Qs) and plasma colloid osmotic pressure pi p was investigated in rabbit knees perfused at constant blood pressure. Intraarticular pressure Pj was independently controlled. Linear relations between transsynovial flow and plasma colloid osmotic pressure established that transsynovial flow obeys the Starling hypothesis. However osmotic conductance, dQs/d pi p, increased 3.9 times when Pj was raised from 6 cm H2O or subatmospheric pressure to 18 cm H2O--the "yield phenomenon." Comparison of the effects of pi p and capillary pressure revealed no major change in the osmotic reflection coefficient of the blood-joint barrier to albumin upon raising Pj. The large increase in osmotic conductance was predicted quantitatively by a previous model (prediction 3.8 X) based on increases in extravascular (intimal) conductance as a function of extravascular pressure. It is argued that capillary endothelium is not the sole significant hydraulic resistance in this pathway. In the terminology of Intaglietta and de Plomb (1973) synovial capillaries are functionally intermediate between "tubes" and "tunnels." PMID- 3343937 TI - The selective response to adenosine of renal microvessels from hamster explants. AB - The present study was undertaken to investigate the effect of adenosine on the microvasculature of the hamster kidney and the possibility of angiotensin II mediation. Renal tissue from neonatal hamsters was grafted into the cheek pouch of 33 adult hamsters. Seven to twelve days later the renal microcirculation was studied. Adenosine was tested on the pre- and postglomerular arterioles as well as on cheek pouch arterioles before and after applying an AII antagonist, saralasin. Adenosine dilated the cheek pouch arterioles and constricted the preglomerular arterioles in a dose-dependent manner. Adenosine had no effect on postglomerular arterioles. The renal vasoconstriction persisted as long as adenosine was present. Theophylline reduced the adenosine-mediated vasoconstriction of the afferent arteriole in a dose-dependent manner. These changes were not altered in the presence of saralasin at various doses, one of which was 20-fold greater than that required to abolish the vasoconstrictor response of a test dose of angiotensin II. This study indicates that the adenosine-mediated vasoconstriction of the preglomerular microvessels is not mediated via the renin-angiotensin system but may be a direct effect of adenosine. PMID- 3343938 TI - Colloid osmotic pressure of subcutaneous wick fluid in rats. PMID- 3343939 TI - Assessing the deformation of pulmonary capillaries produced by ventilation. AB - We used a Fourier transform method to compute from the density fluctuation of aortic blood the changes in the blood volume of pulmonary capillaries and the transit time from the capillaries to the aorta. First the time constants of a lagged normal density function capable of simulating the saline dilution through the central circulation were established. Then we decomposed the Fourier transform of the lagged normal density function to determine an attenuation for the estimation of the density fluctuation in blood leaving the capillaries. Regarding the low hematocrit blood in the capillaries as a density indicator, we deduced from the density fluctuation the percentage change of capillary volume for dogs ventilated mechanically. This change was found to range from 3.8 to 5.8% for frequencies within 6 to 20 cycles per minute. Based on this simulation and the delay time of the density fluctuation from the tracheal pressure, we estimated that the transit time for the density indicator being released from the pulmonary capillaries to the aorta was 45% of the mean transit time of the central circulation, suggesting that the releasing sites are midway of the pulmonary capillaries. PMID- 3343940 TI - A comparative study: perfusion of the micro- and macrocirculation as a function of the hematocrit value. AB - The fluidity (the inverse of viscosity) of red blood cell (RBC) suspensions in vivo was estimated by means of microcirculatory measurements such as RBC flow velocity, micropressure in arterioles and venules, and vessel geometry, and by means of simultaneous macrocirculatory measurements such as volume flow and perfusion pressure in the whole organ. These in vivo data were compared to in vitro data obtained by viscometry. The experiments were performed on the isolated rat mesentery perfused with a nonaggregating and an aggregating suspension: Human RBC were either suspended in Ringer's or Ficoll 400 solution. The tissue was perfused at various perfusion pressures and hematocrit values. The microcirculatory perfusion was recorded by means of microscopy using a video TV system. Five major results have been identified: First, microfluidities calculated from velocity data in capillaries of the mesenteric membrane were almost identical to the fluidities calculated from macroflow data (volume flow rates and perfusion pressure in the whole organ). Second, in vivo fluidities of both suspensions decrease with increasing hematocrit value but seem to be independent of driving pressure between 4 and 10 kPa. Third, the fluidity of the Ficoll suspensions is lower than the fluidity of the Ringer's suspensions by the same ratio as the continuous phases. Fourth, the in vivo fluidities of the Ringer's suspensions and the Ficoll suspensions for hematocrit values from 20 to 70% and a range of wall shear stresses from 0.6 to 1 Pa were higher than those measured in vitro. Finally, it has been quantified that an increasing number of vessels became stagnant (that is packed by red blood cells) at high hematocrit values, low perfusion pressure, and increased aggregability of RBC. PMID- 3343941 TI - Specificity of arginine vasopressin and angiotensin II for microvessels in the hamster cheek pouch after the induction of renovascular hypertension. AB - The present study was undertaken to determine the specificity of the vasoconstrictor activity to angiotensin II (AII) and arginine vasopressin (AVP) on the microcirculation in normal and renovascular hypertensive states. Ten to fourteen days after the induction of hypertension, Syrian hamsters were anesthetized with pentobarbital sodium, the cheek pouch was exposed, and a plastic chamber was placed in situ so the membrane could be suffused with bicarbonate-buffered Ringer's solution (5% CO2, 95% N2, pH 7.4). Third order arterioles (30-45 micron) were identified for study and vessel diameter was measured using a shearing device. In one group of normotensive and hypertensive hamsters, AII was microapplied to the arteriole before and after adding an AVP antagonist to the suffusate. In a second group of similar hamsters, AVP was microapplied to the arteriole before and after adding an angiotensin II blocker, saralasin acetate, to the suffusate. AVP and AII receptor blockade was documented by observing whether the vasoconstrictor effect of either AVP or AII was abolished. Dose-response curves for either peptide were not altered in the presence of the antagonist to the other peptide; however, they were shifted to the left in the RHT hamsters. Neither AVP nor AII receptor blockade altered control resting arteriolar diameters. Thus, it can be concluded that the microvascular response to both AII and AVP are potentiated in RHT and there are no interactions between either AII or AVP with the receptors of the other peptide in these microvessels in normal or RHT hamsters, indicating a high specificity for each peptide to its vascular receptor. PMID- 3343942 TI - Increased vascular resistance due to a reduction in red cell deformability in the isolated hind limb of swine. AB - This study investigated whether red cells with reduced deformability impeded flow through the microcirculation. Red cells were made less deformable in their normal biconcave disc shape by incubation with 2% formaldehyde (fRBCs). The blood supply to the right hind limb was isolated in 26 swine and the femoral artery was instrumented with two fine catheters, a flow probe, and an inflatable occluder. Flow was measured over a range of different perfusion pressures during adenosine induced vasodilation under control conditions (C) and during an infusion of fRBCs at 1 ml/kg per minute (not to exceed 20 ml) into the femoral artery. At the same perfusion pressure (P), flow was significantly reduced 5 min after the fRBC infusion: Flow at P = 20 mm Hg, C = 41 ml/min vs fRBC = 10 ml/min; at P = 40, C = 160 ml/min vs fRBC = 79 ml/min; and at P = 60, C = 278 ml/min vs fRBC = 147 ml/min, with P less than 0.02 for all comparisons. Flow was still significantly reduced 15 min after the fRBCs, but by 30 min, it had returned to the control value. Chromium-51-labeling of red cells revealed that about one-third of fRBCs was trapped in the microcirculation compared to less than 3% of normal cells. This reduction in flow with fRBC infusion was not altered by alpha blockade, indicating that adrenergically mediated spasm was not responsible for the reduced flow. Aspirin 35 mg/kg iv completely prevented the reduction in flow despite an absence of change in the percentage of fRBCs trapped. Thus, red cells with reduced deformability infused into the circulation caused a significant, but transient, reduction in flow. The reduction in flow was not primarily related to entrapment of the abnormal RBCs, but may be mediated through platelet aggregation or release of potent vasoconstrictor substances from platelets or endothelial cells. PMID- 3343944 TI - The cause of leg cramps and knee pains: an hypothesis and effective treatment. AB - Cramps and pains of the lower extremities along with stiffness and pains in the knees are common complaints in the general population. Because the etiology and development of these disorders are poorly understood, treatment has been haphazard, for the most part unsuccessful, and occasionally dangerous. The diagnosis of "arthritis" is often incorrect; when osteoarthritis is present it is frequently not the cause of the pain. We name these maladies the "stiff leg syndrome" and hypothesise that they are caused by muscle and tendon shortening which came about as a direct result of modern civilization; the popular practice of squatting close to the ground to defecate, cook and eat was replaced by a more "civilized" practice of sitting high on toilets and chairs. We discuss several simple stretching exercises which mimic the effects of squatting and frequently result in immediate and dramatic relief of symptoms. PMID- 3343943 TI - Etiology of late developing incisional hernias--the possible role of mechanical stress. AB - The etiology of incisional hernias that develop a year or more after laparotomy is not understood. This subset of incisional hernias is not associated with the etiologic factors usually implicated in incisional hernia formation. Mechanical stress is known to have a profound influence on the structure of both normal and wounded tissue. It is hypothesised that mechanical stress plays an important role in the development of late incisional hernias. PMID- 3343945 TI - Is there too little or too much cholinergic activity in amyotrophic lateral sclerosis? AB - It is suggested that amyotrophic lateral sclerosis may be caused by a succinyl choline-like molecule which binds tightly to acetyl choline receptors. The formation of such a molecule might be catalysed by heavy metals. PMID- 3343946 TI - Epigenesis and the evolution of the human brain. AB - This article proposes an hypothesis for the evolution of the human brain. It is based on the concepts of (i) regulation of nerve cell proliferation, and (ii) selective stabilisation of synapses during development. The former process is supposed to be rigidly regulated by the genome, while the latter (selective stabilisation) is proposed as developing in a more plastic manner. It is suggested here that genetic alterations of the regulation of neuroblast proliferation led to epigenetic rearrangements in selective synapse stabilisation, thus producing significant changes in cerebral connectivity. This view is in agreement with the punctuationalist theory of human evolution, and differs from other approaches to human nature, such as structuralist grammar and sociobiology. PMID- 3343948 TI - Talking sense in surgery. PMID- 3343947 TI - Oestrogen therapy after the menopause--boon or bane? PMID- 3343949 TI - Important changes in the emergency management of acute asthma in children. PMID- 3343950 TI - Non-contraceptive exogenous oestrogen therapy and breast cancer. AB - Previous evidence of an increased risk of breast cancer in association with the use of non-contraceptive exogenous oestrogen therapy has not been consistent. In this population-based case-control study of breast cancer (comprising 451 case control pairs in all) the relationship between the use of non-contraceptive exogenous oestrogen therapy and the risk of breast cancer was examined in the 281 case subjects and 288 control subjects (262 case-control pairs) who were postmenopausal, since the major reported indication for the use of exogenous oestrogen therapy is for the relief of menopausal symptoms. "Ever use" of exogenous oestrogen therapy was associated with an adjusted relative risk of 1.03 (95% confidence interval, 0.62-1.69). The risk of breast cancer was not associated with the duration of use, years since first use, or years since last use of exogenous oestrogen therapy. Stratified analyses of breast cancer showed a 35% increase in risk in nulliparous women that is associated with the use of exogenous oestrogen therapy, a 40% reduction in risk in women with a history of benign breast disease (both statistically not significant), and a statistically significant 70% reduction in risk in women with a history of bilateral oophorectomy. The results of this study should be weighed against those of several earlier studies which suggest caution in the prescription of replacement oestrogen therapy for those women who are known already to be at an increased risk of breast cancer. PMID- 3343951 TI - Knowledge and attitudes of Victorian medical practitioners in relation to the acquired immunodeficiency syndrome. AB - A stratified random sample of Victorian medical practitioners was surveyed to determine doctors' knowledge of and attitudes to the acquired immunodeficiency syndrome (AIDS). The results of this survey have shown that the knowledge level of a representative sample of medical practitioners in Victoria about AIDS was satisfactory at the beginning of a continuing educational campaign. The knowledge level varied according to the age of the doctor and the specialty of medicine that was practised. Attitudes towards and management practice of AIDS varied according to the specialty and rarely correlated with the knowledge level of the doctor. The majority of doctors who were surveyed had already received queries about AIDS from their patients, and over 90% of doctors thought that medical practitioners have a role to play in educating and counselling patients about AIDS (including preventive measures). In addition, the majority of doctors were receptive to receiving more information about AIDS. PMID- 3343952 TI - Psittacosis--a review of 135 cases. AB - We reviewed retrospectively 135 cases of serologically-confirmed psittacosis that were admitted to Fairfield Hospital between January 1, 1972 and March 31, 1986. The average age of the patients was 46 years. The majority (85%) of patients described a history of recent exposure to birds. The clinical features, investigations, treatment and subsequent response were analysed in 129 patients. Psittacosis was a well-defined illness that was characterized by an abrupt onset of fever, rigors, sweats, and prominent headache, and a mild dry cough which appeared late frequently. However, respiratory symptoms were absent in 18% of patients. Diarrhoea and sore throat were occasional complaints. Over 90% of cases had an abnormal chest x-ray film, or abnormal chest signs, or a combination of both. Most patients had a normal leukocyte count. Tetracycline drugs were used for treatment in 87% of the patients. Defervescence occurred in 92% of patients after 48 h of tetracycline treatment. There were no recrudescences of psittacosis and no fatalities. The clinical diagnosis of psittacosis can be made early usually, particularly in the presence of pneumonitis on a chest x-ray film and a positive history of bird contact. Treatment with doxycycline (100 mg twice a day for 14 days) is recommended. PMID- 3343953 TI - The accuracy of manual diagnosis for cervical zygapophysial joint pain syndromes. AB - The ability of a manipulative therapist to diagnose symptomatic cervical zygapophysial joint syndromes accurately was evaluated in a series of 20 patients. In 11 patients the presence, or absence, of a symptomatic joint was established by means of radiologically-controlled diagnostic nerve blocks. These patients were assessed by the manipulative therapist, without knowledge of the medical diagnosis. Another nine patients were first seen by the manipulative therapist whose diagnosis was then evaluated by means of diagnostic blocks. The manipulative therapist identified correctly all 15 patients with proven symptomatic zygapophysial joints, and specified correctly the segmental level of the symptomatic joint. None of the five patients with asymptomatic joints was misdiagnosed as having symptomatic zygapophysial joints. Thus, manual diagnosis by a trained manipulative therapist can be as accurate as can radiologically controlled diagnostic blocks in the diagnosis of cervical zygapophysial syndromes. However, before generalized claims about the reliability of manual diagnosis can be made, further studies of this nature are required to validate intertherapist reliability and the ability of manual techniques to diagnose other spinal pain syndromes. PMID- 3343954 TI - Continuing medical education. Part 5. Mandatory continuing medical education. PMID- 3343955 TI - Introduction of a computer-based oncology patient-care system in a teaching hospital. AB - This report describes a computer-based patient-care system for oncology that provides physicians, nurses, medical students and associated health-care personnel with the means to retrieve data and reports that will enhance greatly their capacity to make informed decisions regarding patient management; at the same time such a system provides adequate safeguards for the confidentiality of information. The system provides information from all clinical laboratories, nursing staff observations, and pharmacy, radiology, pathology and outpatients departments. In addition, the system generates treatment plans that relate directly to day-to-day patient management, covering all aspects of patient care. More extensive research data, demographic data and reports are available from the computer's large database. This computer system is called the Oncology Research Centre Information System (ORCIS). The development of ORCIS has been a major initiative of the NSW State Cancer Council, which is encouraging teaching hospitals in New South Wales to consider this system. The aim of this initiative is to try to prevent the development of many different computer systems in New South Wales, which would cause further confusion in the management of medical information. PMID- 3343956 TI - Bilateral carpal tunnel syndrome and galactorrhoea. PMID- 3343957 TI - Dual-chamber pacing in the cardiomyopathy of primary amyloidosis. AB - Cardiac function in a 75-year-old woman with primary amyloidosis and a restrictive cardiomyopathy deteriorated markedly after the occurrence of high grade atrioventricular block. Atrial synchronous cardiac pacing, which was unreported previously in this setting, produced a marked improvement in cardiac performance. PMID- 3343958 TI - Zygomycosis requiring amputation of the hand: an isolated case in a patient receiving haemodialysis. AB - A case of zygomycosis due to Rhizopus microsporus variety microsporus in a patient who was receiving haemodialysis is described. This infection resulted in amputation of the right hand. Criteria to identify the fungus are presented. The pathogenesis and treatment of zygomycosis are discussed. PMID- 3343959 TI - Risks of human immunodeficiency and hepatitis B viral infections in intravenous drug abusers. PMID- 3343960 TI - Mammography and breast-cancer screening. PMID- 3343961 TI - Occipital cortical "angina" induced by nifedipine. PMID- 3343962 TI - Generic overdosage. PMID- 3343963 TI - Advertising insert on "The specialty of oral and maxillofacial surgery". PMID- 3343964 TI - Prevalence of Chlamydia trachomatis. PMID- 3343966 TI - The golden age of medicine: 1966-1980. PMID- 3343967 TI - The Missouri arthritis program. Legislation, implementation and funding of a Regional Centers program. PMID- 3343965 TI - Drugs for treatment of deep fungal infection. PMID- 3343968 TI - Androgen deficient osteoporosis. PMID- 3343969 TI - Studies on the specificity of the IgA-binding lectin, jacalin. AB - The interactions of IgA with the jackfruit lectin, jacalin, were investigated with regard to the specificity of jacalin for species and subclasses of IgA. It was found that jacalin selectively bound to human IgA1, but not to human IgA2, mouse IgA or rat IgA. Binding studies with human IgA1 fragments produced by different IgA1 proteases revealed that jacalin bound to galactose-terminal oligosaccharides in the hinge region of human IgA1. Affinity chromatography employing jacalin-Sepharose provided a means to separate the subclasses of IgA in human whey. PMID- 3343970 TI - Quasi-elastic light scattering of antigen-antibody complexes. AB - Many biological properties of immune complexes (IC) depend upon their size. Quasi elastic light scattering (QLS) was used to measure a mean equivalent hydrodynamic radius (Rh) and variance of the distribution of model IC composed of bovine serum albumin (BSA) as antigen (Ag) and combinations of two or three well-characterized monoclonal antibodies (MAb) which bound noncompetitively to unique epitopes on BSA. With the molar ratio (X) of each MAb to Ag fixed, Rh increased with concn. Rh was maximal at equivalence (X = 0.5) with two MAb and at slight MAb excess (X = 0.67) with three MAb. The largest Rh with two MAb was about 200 A, and Rh was uniformly different amongst the three combinations of two MAb IC. The largest hydrodynamic radius of individual complexes which formed with two MAb was estimated to be about 400 A; even larger individual complexes were formed with three MAb. Size changes following alteration of solution concns were also followed with QLS. Kinetics of two MAb IC association were too fast to observe; dissociation following large dilution (40-fold) required 5-10 min to attain a new steady state, much less at small dilution. With three MAb, Rh dropped sharply in 5 min and became steady after 1-2 hr. These results suggest that conventional chromatographic and ultracentrifugation techniques for studying IC size, involving large dilution and long measurement time, provide misleading results. Association of three MAb produced a rapid initial increase of Rh in several min, followed by diverse behavior which depended upon concn. From high to low concn, these included (1) exponential growth of Rh with time and appearance of visible macroscopic particles; (2) metastable states for several hr followed by slow growth to large size over several days, leading to formation of particles; and (3) rapid growth to steady state conditions with no visible particles. This heretofore unobserved equilibrium and kinetic behavior of model IC in solution may be reflected in the behavior of more complex, naturally occurring IC. PMID- 3343971 TI - Immunoglobulin G dimer: an idiotype-anti-idiotype complex. AB - Immunoglobulin G (IgG) prepared from pooled human plasma contains variable amounts (up to 40%) of IgG dimer whereas IgG isolated from the plasma of a single individual is essentially monomeric. The amount of dimer increases with the number of donors contributing to the plasma pool from which the IgG is prepared. Dimerization is reversed by increasing the temp or decreasing the pH. Two intact antibody-combining sites (paratopes) are required for optimal dimer formation; the Fc region is unnecessary. These findings strongly suggest that IgG dimer consists of idiotype-anti-idiotype pairs formed between molecules of IgG from different individuals, and that a mechanism exists for suppressing idiotype-anti idiotype formation in vivo. PMID- 3343972 TI - Purification of Par j I, the major allergen of Parietaria judaica pollen. AB - A component of Parietaria judaica pollen extract, previously identified as the major allergen, then reported as Pj10 and hereafter denominated Par j I has been isolated by a combination of 65% ammonium sulphate salt precipitation and gel filtration and an Ultrogel AcA54 column. The purified allergen appeared essentially homogeneous on gel filtration HPLC. The mol. wt of Par j I was estimated by electrophoretic and chromatographic techniques. All results gave values in a range from 13 K to 25 K. Analysis in SDS-PAGE under reducing conditions revealed a broad band corresponding to a mol. wt of 10 K, which retained allergenicity when tested with a patients serum pool. CIE and CRIE patterns of the isolated Par j I displayed the two precipitating lines already reported as those exhibiting the highest IgE-binding ability. Par j I showed a specific allergenic activity about 10-fold higher than that of the whole extract and was demonstrated to be the major allergen of Parietaria judaica as assessed in 25 sensitive human sera. PMID- 3343973 TI - Jacalin: isolation, characterization, and influence of various factors on its interaction with human IgA1, as assessed by precipitation and latex agglutination. AB - An IgA1-specific lectin, Jacalin, was isolated from dried seeds of the jackfruit, Artocarpus integrifolia, by affinity binding to IgA1-Sepharose and elution with D galactose. Jacalin is a glycoprotein with two non-covalently bound subunits (15 and 18 K). Interactions between Jacalin and human Igs were studied by precipitation in gel and in solution, and by agglutination of IgA1-coated latex by Jacalin. Jacalin precipitated only with IgA1-containing samples, including monomers, polymers, monoclonal, polyclonal and secretory IgA1, but not IgA2 of both A2m(1) and A2m(2) allotypes, nor with IgG1, 2, 3 and 4, IgM, IgD, and IgE; after neuraminidase treatment, only IgA1 and IgD were precipitated. Jacalin had a relatively broad pH range of activity in both precipitation and agglutination of IgA1-latex. Bivalent metal cations (Ca, Mg, Mn, Cu, Zn, Co, Cd), EDTA, Triton X 100, Tween-20, Na deoxycholate and ionic strength did not influence these reactions. Na dodecylsulphate, guanidine and urea inhibited the reactions whereas NP-40 rather enhanced them. Among 39 types of sugar tested, 10 displayed inhibitory activity, decreasing in the following order: p-nitrophenyl-alpha-D galactopyranoside, 1-O-methyl-alpha-D-galactopyranoside, D-melibiose, p nitrophenyl-beta-D-galactopyranoside, GalNAc, stachyose, 1-O-methyl-alpha-D mannopyranoside, D-galactose, D-galactosamine and 1-O-methyl-alpha-D glucopyranoside. IgA1, treated with neuraminidase or not, but not the other human Igs, was also an excellent inhibitor of agglutination, being more powerful than the best sugars studied. Only neuraminidase-treated IgD was also inhibitory, but less so than IgA1. Jacalin preferentially bound to alpha-linked non-reducing D galactose. The configuration of OH-groups at C-2, C-4 and C-6 of D-galactose was important for the reaction. Jacalin recognizes terminal Gal beta 1-3GalNac-, as in the IgA1-hinge, and/or GalNAc-, but not Gal beta 1-4GlcNAc-, nor Gal beta 1 6GlcNAc-, nor their sialylayted extensions. Latex agglutination and its inhibition assay are particularly well suited for the study of these lectin glycoprotein interactions. PMID- 3343975 TI - A model for the hapten-induced enhancement of monoclonal antibody binding in ELISA. AB - The unusual binding properties of three anti-phosphocholine (PC) monoclonal antibodies (MAbs) in ELISA has been reported [Hall T. J. (1987) Molec. Immun. 24, 773-777]. These MAbs gave reproducible 2-4 fold increases in binding to PC protein coated plates in the presence of PC (approximately 2 mM), nitrophenyl PC (approximately 10 micron) and other PC analogues. A model is proposed here in which the complementary and opposite binding of hapten and PC-protein in the combining sites of these MAbs explains the hapten enhanceable binding in ELISA. PMID- 3343974 TI - Monoclonal antibodies to bovine serum albumin: affinity and specificity determinations. AB - A panel of 12 monoclonal antibodies (MAb) to bovine serum albumin (BSA) was developed and characterized as to their physiochemical and immunological properties. Affinity constants of the MAb varied over a wide range from 10(5) to 10(8) M-1. MAb were assembled into several groups of non- or minimally interacting antibodies by analysis of competitive binding experiments, and BSA domain and subdomain specificities of the MAb were assigned by analysis of results of MAb binding to purified BSA fragments. Further fine specificity delineation was accomplished by examination of cross-reactivity patterns to several mammalian albumins. The data suggest that some of the low affinity MAb recognize sites on different portions of the BSA molecule, indicating that similar epitopes exist on different domains of the BSA molecule. PMID- 3343976 TI - Ligand binding by murine IgM antibodies: intramolecular heterogeneity exists in certain, but not all, cases. AB - The ligand binding properties of eight hybridoma-derived murine anti-DNP IgM(kappa) antibodies were analysed by equilibrium dialysis. Four of these proteins exhibited the expected valances of approximately 10 and relatively low affinities (less than or equal to 2.2 x 10(5) M-1). The remaining four proteins exhibited valences of considerably less than 10 (less than or equal to 8) and relatively high affinities (greater than 10(6) M-1). When these proteins were subjected to two cycles of lyophilization, those of the former group were observed to still exhibit approximately 10 sites per molecule with homogeneous affinities similar to those of the respective untreated molecules. However, molecules in the latter group (valences of less than or equal to 8) were observed to exhibit only five to six binding sites subsequent to lyophilization with no changes in affinities. When the reductive subunits from each of the IgM(kappa) proteins were subjected to trypsinization, two different patterns were observed in terms of the yields of Fab mu fragments. Each of the proteins originally exhibiting approximately 10 binding sites yielded greater than 90% of the expected Fab mu fragments. In contrast each of the proteins exhibiting less than or equal to 8 binding sites yielded only approximately 50% of the expected Fab mu fragments. Collectively these results indicate the existence of at least two different forms of murine IgM molecules, those with approximately 10 homogeneous, relatively stable sites and those with only approx. five stable sites. It is suggested that these intramolecular functional differences may be attributable to intramolecular conformational differences. PMID- 3343977 TI - Spermatocyte chromosome alterations in mice inoculated with antirabies vaccine and tetanus toxoid separately and in combination. AB - The genotoxic potential of antirabies vaccine (ARV) and tetanus toxoid (TT) inoculated separately and in combination was evaluated by spermatocyte chromosome analysis in mice. Adult males were vaccinated with a dose of 1 ml/kg ARV once daily for 7 days, or with a dose of 1 ml/kg TT once only, or with both (TT being administered along with the last dose of ARV). Spermatocytes were analyzed over 1 6 post-vaccination weeks for numerical and structural changes as well as for univalent formation. Controls were age matched non-vaccinated males. Significantly high incidences of structural aberrations from wk 4 onwards and at wk 6 following inoculation of ARV and TT, respectively, suggested susceptibility of stem cells to the vaccines. Combined vaccination (ARV plus TT) showed an additive effect. Occurrence of univalents involving autosomes as well as sex chromosomes was very common in all the vaccinated groups, the sex chromosomes being prevalently involved. Structural aberrations showed a positive correlation with time, while univalent formation showed a negative correlation. It appears that factors for clastogenicity and univalent formation are different for both the vaccines. PMID- 3343978 TI - Cytogenetic effects of malathion insecticide on somatic and germ cells of mice. AB - Male mice dermally exposed to single or multiple treatment (5 days/2 weeks) showed that the ability of malathion to induce chromosome aberrations in somatic (bone marrow) and germ cells (primary spermatocytes) was related to the type of treatment and dose used. Statistically significant increases of chromosome aberrations in bone marrow cells occurred after single treatment (500 and 2000 mg/kg body wt) when chromatid gaps were included and after multiple treatment (250 and 500 mg/kg) when they were excluded. No dose-response relationships were observed for either treatment. In germ cells, malathion induced a significant increase of univalents in both types of treatment but structural chromosome aberrations were induced only by multiple treatment. Malathion induced a significant decrease of the mitotic indices in the bone marrow. PMID- 3343979 TI - In vivo and in vivo/in vitro kinetics of cyclophosphamide-induced sister chromatid exchanges in mouse bone marrow and spleen cells. AB - In several acute and chronic exposures to various chemicals in vivo and in vitro, the average sister-chromatid exchange (SCE) frequencies in human, mouse, rat, and rabbit lymphocytes generally decrease with time following treatment. The rate of this decline varies, but little data have been published pertaining to the comparative kinetics of SCEs both in vivo and in vivo/in vitro (exposure of animals to the test compound and culturing of cells) simultaneously in the same tissues. In this study, a single dose of cyclophosphamide (40 mg/kg) was injected for varying periods (6-48 h) and its effects, as assessed by the induction of SCEs, were analyzed under both in vivo and in vivo/in vitro conditions in mouse bone marrow and spleen cells. In vivo, the cyclophosphamide-induced SCEs increased with increasing time up to 12 h, stayed at approximately the same level until 24 h, and then decreased with increase in post-exposure time. However, the SCE levels remained significantly higher than controls at 48 h post-exposure time in both bone marrow and spleen cells. Under in vivo/in vitro conditions, the SCEs in bone marrow decreased with increase in post-exposure time until reaching control values by 48 h post exposure. However, in spleen cells, the decrease in SCE level was gradual, and by 48 h post-exposure time, the cells still had approximately 6 times higher SCEs than the control values. These results suggest that there are pharmacokinetic differences for cyclophosphamide in mouse bone marrow and spleen. Also, there is a differential SCE response to cyclophosphamide under in vivo and in vivo/in vitro conditions. PMID- 3343980 TI - Strain difference in the micronucleus test. The Collaborative Study Group for the Micronucleus Test. AB - The Collaborative Study Group for the Micronucleus Test, a task group of the Environmental Mutagen Society of Japan, has earlier addressed the question of sex difference as a source of variation in the micronucleus test. Strain difference, another issue in test protocols requiring urgent clarification, was selected as the subject of the second study. Male mice of strains Slc:ddY (ddY), CRJ: CD 1(ICR) (CD-1), Slc:BDF1 (BDF1), and ms:Hal (ms) were treated with 6 different chemicals chosen from various classes of micronucleus inducers: colchicine, 7,12 dimethylbenz[a]anthracene, ethyl methanesulfonate, N-ethyl-N-nitrosourea, 6 mercaptopurine, and potassium chromate. All 4 strains gave positive results with all 6 chemicals, although ms tended to show the highest responses. ddY and CD-1 were low responders, while BDF1 was intermediate between ms and the other two. Although ms seemed superior to the other strains, its high responses became manifest mostly at high dose levels. ms was not always the most sensitive strain; it responded moderately to ethyl methanesulfonate. Also the background level of micronucleated polychromatic erythrocytes was the highest in ms, but this did not explain the apparent high sensitivity of this strain. Despite the strain differences, it can be concluded that any of the other strains used seems to suffice as a tester for the micronucleus test. PMID- 3343981 TI - Mutagenicity and clastogenicity of proflavin in L5178Y/TK +/- -3.7.2.C cells. AB - We evaluated the ability of proflavin to induce specific-locus mutations at the heterozygous thymidine kinase (tk) locus of L5178Y/TK +/- -3.7.2C mouse lymphoma cells, which appears to permit the recovery of mutants due to single-gene and chromosomal mutations. Proflavin was highly mutagenic at the tk locus, producing 724-965 TK mutants/10(6) survivors (background = 56-85/10(6); survival = 29-32%). Most of the mutants were small colonies, which suggested that proflavin may induce chromosomal mutations. The potent clastogenicity of proflavin was confirmed by cytogenetic analysis for chromosomal aberrations. At the highest dose analyzed (1.5 micrograms/ml), proflavin produced 82 aberrations/100 metaphaes (background = 2/100). The large-colony TK mutant frequency produced by proflavin (48-109/10(6) survivors; background = 23/10(6); survival = 57-61%) was similar to published HPRT mutant frequencies produces by proflavin in L5178Y and CHO cells (50-100/10(6) survivors; background = 2-50/10(6); survival = 50-62%). These results lead to the conclusion that proflavin is a potent clastogen and induces a high frequency of small-colony TK mutants; however, it induces a low frequency of HPRT mutants and a low frequency of large-colony TK mutants. PMID- 3343982 TI - Cytotoxic and mutagenic effects of emodin on cultured mouse carcinoma FM3A cells. AB - Employing a suspension culture of a mouse mammary carcinoma cell line, FM3A cells, the cytotoxicity and induced mutagenicity of emodin (EM) were examined and compared with those of 2-hydroxy-emodin (2-OH-EM), which was identified as an active form of EM in the Ames/microsomes assay. EM was cytotoxic to FM3A cells in concentrations of 1-10 micrograms/ml, and induced 6-thioguanine-resistant (6TGr) mutation. 2-OH-EM was a little more toxic than EM, but induced little mutation. PMID- 3343983 TI - Genotoxic effects of paracetamol in V79 Chinese hamster cells. AB - Paracetamol was studied for possible genotoxic effects in V79 Chinese hamster cells. Paracetamol (0.5 mM for 30 min) reduced the rate of DNA synthesis in exponentially growing V79 cells to about 50% of control. A further decrease in the DNA synthesis was seen during the first 30 min after termination of paracetamol exposure. Paracetamol (3 and 10 mM for 2 h) caused a small increase in DNA single-strand breaks, as measured by the alkaline elution technique. After 16 h elution, the amount of DNA retained on the filters was 79 and 70% of controls in cells treated with 3 and 10 mM paracetamol respectively. No indication of DNA damage was seen in measuring the effect of paracetamol (0.25-10 mM for 2 h) on unscheduled DNA synthesis in growth-arrested cultures of V79 cells. At the highest concentrations (3 and 10 mM paracetamol), decreased unscheduled DNA synthesis was observed. Also UV-induced DNA-repair synthesis was inhibited by 3 and 10 mM paracetamol. DNA-repair synthesis was, however, inhibited at a much higher concentration than that inhibiting replicative DNA synthesis. The number of sister-chromatid exchanges (SCE) increased in a dose dependent manner on 2 h exposure to paracetamol from 1 mM to 10 mM. At the highest dose tested (10 mM), the number of SCE increased to 3 times the control value. Co-culturing the V79 cells with freshly isolated mouse hepatocytes had no further effect on the paracetamol induced sister-chromatid exchanges. The present study indicates that paracetamol may cause DNA damage in V79 cells without any external metabolic activation system added. PMID- 3343984 TI - Cytogenetic monitoring of hospital workers exposed to low-level ionizing radiation. AB - In the present study the cytogenetic effects in hospital workers exposed to low level radiation were evaluated. Samples of peripheral blood were collected from 63 subjects working in radiodiagnostics and from 30 subjects, working in the same hospitals, who were used as controls. A higher number of cells with chromosome type aberrations (CA) was observed in the exposed workers vs. the controls and the difference was statistically significant (p less than 0.05). No correlation was, on the contrary, found between CA and years of exposure. A significant difference was observed in the incidence of cells with CA between smokers and non smokers, but in the control group only. In contrast, in the workers exposed to ionizing radiation, the frequency of cells with CA was very similar in smokers and non-smokers. PMID- 3343985 TI - Multifocal acquired demyelinating neuropathy masquerading as motor neuron disease. AB - We report five patients with pure motor neuropathy characterized by multifocal weakness, muscle atrophy that was sometimes profound, cramps, and fasciculations with relatively preserved reflexes. The clinical picture led to an initial diagnosis of motor neuron disease in all cases, but nerve conduction studies revealed multifocal conduction block confined to motor axons and predominantly involving proximal nerve segments. Routine sensory nerve conduction studies, ascending compound nerve action potentials, and somatosensory evoked potentials were all normal even through nerve segments in which motor conduction was severely blocked. Onset of symptoms was insidious, and progression was indolent. In two cases, after many years of neuropathy, sensory abnormalities developed but remained clinically trivial. These unusual cases probably have the same pathogenesis as previously described patients with persistent multifocal conduction block. Distinction from motor neuron disease is critical, since chronic demyelinating neuropathy may respond to treatment. PMID- 3343986 TI - Chloroquine myopathy and myasthenia-like syndrome. AB - A young woman on chronic corticosteroid treatment for systemic lupus erythematosus developed a myasthenia-like syndrome 7 weeks after starting chloroquine therapy. Discontinuation of chloroquine allowed symptomatic and immunological remission within 6 months. Ocular symptoms reappeared following a second short course of chloroquine. A motor-point biopsy revealed a vacuolar myopathy with membranous bodies in intramuscular nerves. We discuss the possible role of chloroquine in the pathogenesis of a myasthenia-like syndrome. PMID- 3343987 TI - Expression of fiber type specific proteins during ontogeny of canine temporalis muscle. AB - The canine masticatory muscles contain a unique adult fiber type composition and different contractile protein isoforms than do adult limb muscles. To determine when these characteristic proteins are expressed during development, samples from canine temporalis (masticatory) and pectineus (limb) muscles were compared between 55 days gestation and 60 days postpartum by histochemical, biochemical, and immunocytochemical analysis. At 55 days gestation and 3 days postpartum, both muscles contained identical histochemical type 2C fibers, native myosin isozymes, and myosin light and heavy chains. By 14 days postpartum, fiber-type expression in these muscles diverged, with resultant formation of type 1 and type 2M fibers in the temporalis muscle and type 1 and 2A fibers in the pectineus muscle. The distinctive myosin isoforms, light chains, and heavy chain of the temporalis muscle were also expressed 2 weeks postpartum. Based on the methods used in this study, we conclude that (1) the temporalis muscle develops from embryonic fibers that initially contain a myosin indistinguishable from embryonic limb muscle fibers, suggesting they have a common precursor, and (2) the myosin light chains and heavy chain unique to the temporalis muscle are initially expressed 2 weeks postpartum. PMID- 3343988 TI - Axilla to elbow radial nerve conduction. AB - Numerous techniques that evaluate radial nerve conduction from the axilla or supraclavicular fossa to the elbow have been reported. A shortcoming of most protocols is determining the precise radial nerve length as it proceeds along the spiral groove. The present study dissected out and measured directly eight cadaver radial nerves from the axilla to the elbow. These values were compared with a new surface tape measurement technique from axilla to elbow across the bicep muscle, obstetrical calipers over this region, and a surface determination approximating the course of the radial nerve posteriorly in the spiral groove. The anterior surface tape-measuring procedure compared most favorably with the actual anatomic length. Nerve conduction velocities were then calculated in 20 volunteers using all 3 techniques and compared with the median nerve in the arm. The anterior and posterior tape measurements yielded a conduction velocity of 72.5 +/- 4.7 and 86.6 +/- 7.0 m/s, respectively, whereas the caliper resulted in 65.7 +/- 3.9 m/s. We conclude that proximal radial nerve length assessment employing an anterior tape measurement from axilla to elbow across the bicep musculature is precise and compares favorably with the actual anatomic length of the radial nerve. PMID- 3343989 TI - Axonal conduction velocity and force of single human motor units. AB - Tungsten microelectrodes of the type used for microneurography have been used to record motor units selectively from the first dorsal interosseous and abductor pollicis brevis muscles of normal subjects and patients who had had complete sections of the ulnar or median nerve. After determining the recruitment threshold and the twitch tension (spike-triggered averaging) of a single unit, its nerve was stimulated at the wrist and the elbow using surface electrodes. By adjusting the position of the surface electrode and the stimulus intensity and by using computerized subtraction of responses just above and below threshold for a given unit, the same motor unit could often be identified in response to stimulation at both sites and its conduction velocity determined. The twitch tension and recruitment threshold of the motor units were closely correlated with the conduction velocity of the motor axons in normal subjects. Preliminary data from patients suggests that this method should be applicable to patients with a number of neuromuscular disorders. PMID- 3343990 TI - Stretch-induced spinal accessory nerve palsy. AB - Left spinal accessory nerve palsy occurred in a young man when he quickly turned his head to the right while his shoulders were pulled down by heavy hand-held objects. Electrophysiologic studies demonstrated partial axonotmesis of the spinal accessory nerve branches innervating the sternocleidomastoid and upper and middle trapezius and complete axonotmesis of spinal accessory branches to the lower trapezius. There was a separate, although functionally minor, cervical plexus innervation of the lower trapezius. PMID- 3343991 TI - Simulation of concentric needle EMG motor unit action potentials. AB - Computer simulations of motor unit action potentials (MUAPs) as measured by a concentric needle (CN) electromyography (EMG) electrode in normal motor units (MUs) indicated that the MUAP amplitude is determined mainly by the proximity of the electrode to the closest muscle fiber. The area and duration of the simulated MUAPs were affected by all muscle fibers in front of the active recording surface but mainly by those that were less than 2 and 2.5 mm, respectively, from the active recording surface. The MUAP area was also affected by the proximity of the electrode to the closest muscle fiber. The number of phases of the simulated MUAPs increased when the dispersion of the arrival times of individual muscle fiber APs at the electrode was increased. Increased temporal dispersion of APs decreased the MUAP amplitude and area slightly but did not affect the MUAP duration. It is inferred that different features of the CN MUAP are determined by the distribution of muscle fibers within different portions of the MU territory and thus provide complementary information about the MU architecture. PMID- 3343992 TI - Hexahydrocarbon effects on intermediate filament organization in human fibroblasts. AB - We reported previously that 2,5-hexanedione (2,5-HD), the neurotoxic metabolite of methyl-n-butylketone (MnBK) and n-hexane, induced aggregation of intermediate filaments of the vimentin type in cultured fibroblasts. To determine if these findings have relevance to the mechanism by which these hexacarbons induce their filamentous axonopathy, it was necessary to show that only those hexacarbon analogues that induce focal accumulation of neurofilaments in nerve fibers do aggregate intermediate filaments in fibroblasts. We report here that the nonneurotoxic hexacarbons, 1,6-hexanediol and 2,4-hexanedione (2,4-HD), had no primary effect on intermediate filament distribution in fibroblasts, although the profound, nonspecific cytotoxicity of the latter controverted comparisons with equimolar, effective concentrations of 2,5-HD. Fibroblasts did not metabolize MnBK to 2,5-HD sufficiently to induce reproducible aggregation of intermediate filaments in these cells in culture. PMID- 3343993 TI - The muscle fiber conduction velocity and power spectra in familial hypokalemic periodic paralysis. AB - Surface EMG has been used to determine the average muscle fiber conduction velocity (MFCV) and power spectra of the m. biceps of 10 patients and 15 asymptomatic offspring of a large kinship with familial hypokalemic periodic paralysis (HOPP). The MFCV of the patients was 3.37 +/- 0.35 m/sec (mean +/- SD, n = 9), the median frequency (Fmed) of the power spectra was 55.0 +/- 5.8 Hz (mean +/- SD, n = 9), both values are significantly (P0.001, Student's t-test) lower than the control values: MFCV = 4.55 +/- 0.33 m/sec; Fmed = 88.6 +/- 15.5 Hz (mean +/- SD). In 6 of the 15 asymptomatic relatives, the surface EMG results were also abnormal. It is concluded that the MFCV is reduced in familial HOPP. This results in a predominantly low-frequency content of the power spectra, thereby providing a new model for studying the relationship between the MFCV and the frequency spectrum of surface EMG. Asymptomatic relatives that have inherited the disease probably can be detected with this method. PMID- 3343994 TI - Central motor conduction times using transcranial stimulation and F wave latencies. AB - The purpose of this study was to determine central motor conduction times between the motor cortex and the C8 spinal cord level (MC/C8), the motor cortex and S1 cord level (MC/S1), and C8 and S1 (C8/S1). We stimulated 29 normal subjects with a transcranial high voltage (300-500 V), short duration spike waveform (time constant 50 mu sec) and recorded over the hypothenar or calf muscles. F wave and M response latencies were used to estimate peripheral conduction time. The mean MC/C8 conduction time was 4.4 +/- 0.6 msec. Out of 26 subjects tested, 14 had discernable responses in the calf. The mean MC/S1 conduction time was 13.1 +/- 2.5 msec, and the mean estimated C8/S1 conduction time was 8.5 +/- 2.3 msec. This technique accurately measures conduction time from the motor cortex to the cervical anterior horn cells but is less reliable for monitoring conduction to the sacral cord. These values will facilitate future studies in patients with suspected lesions of the descending motor pathways. PMID- 3343995 TI - Necrotizing myopathy in SJL mice. PMID- 3343996 TI - Facial weakness without ocular weakness in myasthenia gravis. PMID- 3343997 TI - Neuralgic amyotrophy: an increasingly diverse entity. PMID- 3343998 TI - Proton spin-lattice relaxation time of Duchenne dystrophy skeletal muscle by magnetic resonance imaging. AB - By means of proton MRI, the spin-lattice relaxation times (T1 values) of pelvic and leg muscles were measured in Duchenne muscular dystrophy (DMD) patients and normal controls. The bound water fraction (BWF) was calculated from the T1 value obtained. In normal children, the T1 value decreased, and BWF increased with age. In DMD, the T1 value rapidly decreased, from an abnormally high value in the early stages, with the progress of the disease. This reduction of the T1 value in DMD was not the same for all muscles; it was most prominent in the gluteus maximus and least prominent in the sartorius and gracilis muscles. BWF was below normal in the early stages of DMD. It is suggested that both regenerating and degenerating muscle fibers, together with the increased muscle water content, cause the high T1 value and low BWF in the early stages of DMD, whereas replacement of muscle by fat causes the decreased T1 value in the advanced stages. PMID- 3343999 TI - Purification of two Leishmania donovani membrane proteins recognized by sera from patients with visceral leishmaniasis. AB - Two Leishmania donovani membrane proteins recognized by sera from patients with visceral leishmaniasis were purified using species-specific monoclonal antibodies and characterized. The molecular weights of the proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were approximately 70,000 and approximately 72,000, respectively. The 70 kDa protein, which appears as a diffuse band on silver staining, was resolved into a doublet by Western blotting with monoclonal antibody. Though of similar molecular weight and amino acid composition, the two proteins were shown to be distinct by peptide mapping and Western blotting of the purified material. The two proteins are recognized specifically by human visceral leishmaniasis serum and not by serum from cutaneous leishmaniasis or Chagas' disease. These proteins will be useful in developing a direct serodiagnostic assay for visceral leishmaniasis. PMID- 3344000 TI - The biochemical and immunochemical characterisation of the 30 kilodalton surface antigen of Brugia pahangi. AB - The major surface antigen (30 kDa) of Brugia pahangi has been characterised by a number of biochemical and immunochemical means. The 30 kDa polypeptide is a glycoprotein which can be extracted from the worm surface by homogenization in the absence of detergents. The 30 kDa polypeptide can be metabolically labelled with [35S]methionine in adult male and female parasites. In addition small amounts of the 35S-labelled 30 kDa antigen can be detected in the medium of worms cultured in vitro. 125I labelling of the excretory-secretory (ES) products of adult male and female parasites followed by immunoprecipitation and peptide mapping has confirmed the relationship between the surface located 30 kDa polypeptide and that released in vitro. PMID- 3344001 TI - Leishmania major: glycolipid antigens recognized by immune human sera. AB - Extraction of whole promastigotes with a mixture of hexane-isopropanol yielded two carbohydrate-lipid fractions immunologically active against immune sera from patients with cutaneous leishmaniasis (CL): CLF-1 and CLF-2. Thin layer chromatography (TLC) separated both fractions into eight bands labeled A-H. Four of these bands, Rf 0.19, 0.25, 0.39 and 0.48 (A, B, C and E, respectively) were recognized by antibody from patients with CL in a solid phase radioimmunoassay. Antigens were also detected by autoradiography after immunoblotting of TLC. Compound A could be labeled biosynthetically with [3H]oleic acid, [14C]galactose, [14C]mannose, [14C]glucose and [32P]phosphate. B incorporated [14C]galactose, [14C]mannose, [14C]glucose and [14C]myo-inositol. C was labeled with [14C]galactose and [14C]mannose, while E incorporated [14C]glucose, [14C]mannose, [3H]oleic acid and [14C]myoinositol. Two antigens (A and B) could be also labeled on the surface of living promastigotes using galactose oxidase and [3H]sodium borohydride. Experimental data showed that CLF-1 and CLF-2, both carbohydrate containing fractions, had different chromatographic patterns from excreted factor (EF), a polysaccharide antigen from Leishmania. The present study characterizes glycolipid molecules from L. major promastigotes, able to stimulate the immune system from patients with CL. PMID- 3344002 TI - Physicochemical characteristics of non-electrolytes and their uptake by Brugia pahangi and Dipetalonema viteae. AB - The uptake of a diverse set of 14C-labelled non-electrolytes by Brugia pahangi and Dipetalonema viteae was measured relative to the free diffusion of tritiated water. Inulin was used as a non-absorbable surface marker to account for non electrolyte adherent to the surface of the parasite which had not crossed the cuticle. B. pahangi and D. viteae took up the non-electrolytes to a similar degree; a comparison of tissue uptake indices gave a correlation coefficient of 0.99. Worm uptake could not be described by non-electrolyte octanol/aqueous partition coefficients alone. However, greater success was achieved using further descriptors and pattern recognition techniques for data analysis. The whole molecule descriptors log P, molar refraction, melting point, dipole moment and CNDO total energy were obtained from computer chemistry and the literature. Using a linear learning machine to relate uptake to these 5 physicochemical descriptors it was possible to successfully classify non-electrolytes as high or low uptake. Multivariate regression analysis of uptake versus these 5 parameters gave a correlation coefficient of 0.77. However, this was not statistically significant and therefore could not be used for quantitative predictions of substance uptake by worms. This illustrates the value of 'pattern recognition' techniques such as the linear learning machine. Using such 'pattern recognition' methods on a chemically related set of compounds it is anticipated that predictions of uptake can be achieved and improved upon. Such predictions could then be used in drug design. PMID- 3344003 TI - Comparison of several lizard Leishmania species and strains in terms of kinetoplast minicircle and maxicircle DNA sequences, nuclear chromosomes, and membrane lipids. AB - Eight strains of a lizard Leishmania species, L. tarentolae, were compared with four other saurian species [L. hoogstrali, L. adleri, L. agamae and Leishmania sp. LizS], with L. major from man and with Trypanosoma platydactyli, a putative lizard trypanosome, in terms of kinetoplast DNA minicircle and maxicircle sequences and in terms of nuclear chromosome patterns on orthogonal gel electrophoresis. The L. tarentolae strains fell into two major groups, one (group A) consisting of the L. tarentolae strains, UC, Krassner and Trager, derived from an Algerian gecko isolate and the other (group B) consisting of five L. tarentolae LEM strains isolated from geckos in southern France. T. platydactyli TPCL2, which was postulated by Wallbanks et al. to represent the lizard form of a French L. tarentolae strain, was closely related to the UC strain and not to the LEM strains, in all respects analyzed. Leishmania sp. LizS from a Mongolian gecko and L. hoogstrali from a Sudanese gecko showed some sequence similarities to the L. tarentolae strains, but the leishmanias said to be L. adleri from a Kenyan lacertid and L. agamae from an Israeli agamid showed no minicircle sequence similarities with lizard Leishmania and in fact were probably the same species. The maxicircle divergent region was larger in the group B strains than in the group A strains, but there were sequences in common with both groups, and not with L. hoogstrali and L. major. Four strains of L. tarentolae, the four other supposed saurian Leishmania species, three mammalian leishmanias, T. platydactyli and four other trypanosomes, T. cyclops (Malaysian macaque), T. conorrhini (Hawaiian reduviid bug), T. cruzi (man) and T. lewisi (feral rat) were analyzed for their contents of sterols and phosphoglyceride fatty acyl groups. T. platydactyli TPCL2 contained a sterol (5-dehydroepisterol), a phosphatidylcholine fatty acyl group (alpha-linolenic acid) and a phosphatidylethanolamine fatty acyl group (dihydrosterculic acid) characteristic of members of the genus Leishmania and not the genus Trypanosoma. The proportions of those lipids in the free sterol and phosphoglyceride fractions of T. platydactyli TPCL2 most closely resembled those seen in the Leishmania strains from Algerian, French, Mongolian and Sudanese geckos. PMID- 3344004 TI - Purification and characterization of a metabolite-regulated pyruvate kinase from Leishmania major promastigotes. AB - The pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) of Leishmania major promastigotes is a multimer of 59 kDa subunits having an Mr 181000. It is activated by its substrate phosphoenolpyruvate (PEP) in a positively cooperative manner, and heterotropically by fructose 1,6-bisphosphate (FBP). Kinetics with regard to the phosphate acceptor adenosine 5'-diphosphate (ADP), MgCl2, and KCl are hyperbolic and unaffected by FBP. The enzyme is strongly inhibited by the reaction product ATP, as well as GTP and ITP, and to a lesser degree by citrate. Of seven amino acids reported to inhibit the pyruvate kinases of other organisms, none have any effect on the L. major pyruvate kinase in vitro. The enzyme shows its maximum activity at pH 7.0 in the absence of FBP, and at pH 7.6 in its presence. Contrary to previous suggestions, the enzyme appears to be well-suited for a regulatory role in the metabolism of an aerobic organism capable of net glucose synthesis. PMID- 3344006 TI - Long-term growth in juvenile acquired hypothyroidism: the failure to achieve normal adult stature. AB - It has been suggested that complete catch-up growth is achieved with treatment in patients with juvenile acquired hypothyroidism. We tested this assumption by examining long-term growth in 18 girls (mean [+/- SD] age, 11.4 +/- 2.7 years; bone age, 6.2 +/- 3.1 years) and 6 boys (age, 10.6 +/- 4.7 years; bone age, 6.4 +/- 2.7 years) with severe primary hypothyroidism (serum thyroxine level 1.1 +/- 0.3 micrograms per deciliter [13 +/- 4 nmol per liter]). At diagnosis, heights were 4.04 +/- 0.5 and 3.15 +/- 0.4 SD below the mean heights for age of normal girls and boys, respectively. The patients were treated with levothyroxine (3.4 +/- 0.3 micrograms per kilogram of body weight per day) to maintain normal thyroid function. During the first 18 months of therapy, the children's skeletal maturation exceeded the maturation expected for their statural growth, regardless of whether or not they were undergoing pubertal development. Predictions of decreased adult height were based on these observations. At maturity, girls and boys stood approximately 2 SD below normal adult stature, at 149 +/- 5.0 cm and 168 +/- 5.1 cm, respectively. Heights at maturity were also lower than midparental heights (P less than 0.01) and lower than pre-illness standard deviation scores for height (P less than 0.01). The deficit in adult stature was significantly related to the duration of hypothyroidism before treatment (P less than 0.01). We conclude that despite treatment, prolonged juvenile acquired hypothyroidism results in a permanent height deficit related to the duration of thyroxine deficiency before treatment. PMID- 3344005 TI - The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. AB - We evaluated the use of the urinary anion gap (sodium plus potassium minus chloride) in assessing hyperchloremic metabolic acidosis in 38 patients with altered distal urinary acidification and in 8 patients with diarrhea. In seven normal subjects given ammonium chloride for three days, the anion gap was negative (-27 +/- 9.8 mmol per liter) and the urinary pH under 5.3 (4.9 +/- 0.03). In the eight patients with diarrhea the anion gap was also negative (-20 +/- 5.7 mmol per liter), even though the urinary pH was above 5.3 (5.64 +/- 0.14). In contrast, the anion gap was positive in all patients with altered urinary acidification, who were classified as having classic renal tubular acidosis (23 +/- 4.1 mmol per liter, 11 patients), hyperkalemic distal renal tubular acidosis (30 +/- 4.2, 12 patients), or selective aldosterone deficiency (39 +/- 4.2, 15 patients). When the data on all subjects studied were pooled, a negative correlation was found between the urinary ammonium level and the urinary anion gap. We conclude that the use of the urinary anion gap, as a rough index of urinary ammonium, may be helpful in the initial evaluation of hyperchloremic metabolic acidosis. A negative anion gap suggests gastrointestinal loss of bicarbonate, whereas a positive anion gap suggests the presence of altered distal urinary acidification. PMID- 3344007 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1988. A 73-year-old hypertensive man with intracranial hemorrhages 15 months apart. PMID- 3344008 TI - Catch-up growth in hypothyroidism. PMID- 3344009 TI - Steroids and "steroid-sparing" agents in asthma. PMID- 3344010 TI - The risks of lone atrial fibrillation. PMID- 3344012 TI - Cardiac amyloidosis. PMID- 3344011 TI - Verapamil-induced atrial fibrillation. PMID- 3344013 TI - Mediators of bone resorption and hypercalcemia in cancer. PMID- 3344014 TI - Disposition of oocytes and age at menopause. PMID- 3344015 TI - Influence of furosemide on parathyroid hormone levels in hyperparathyroidism. PMID- 3344016 TI - The orphan patient. PMID- 3344017 TI - Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. AB - Previous work based on the relative tissue content of glucose-6-phosphate dehydrogenase isoenzymes suggested that parathyroid adenomas, like primary hyperplasia, may be multicellular (not clonal) in origin. We have reexamined this issue by using two independent molecular genetic methods. We report tumor-cell specific restriction-fragment-length alterations involving the parathyroid hormone gene from two human parathyroid adenomas. These abnormal restriction fragments indicate that in each case a clonal proliferation of cells was present and also suggest that DNA alterations involving the parathyroid hormone locus may be important in the tumorigenesis or clonal evolution of some parathyroid adenomas. In addition, we used a restriction-fragment-length polymorphism in an X linked gene (hypoxanthine phosphoribosyltransferase) to examine the clonality of eight parathyroid adenomas in women. Of these eight adenomas, six had the DNA hybridization pattern of monoclonality, and two had an equivocal pattern. None of five hyperplastic parathyroid glands had a monoclonal pattern. We conclude that some (and perhaps many) single parathyroid adenomas are monoclonal neoplasms. Our observations suggest that there is a fundamental biologic difference between parathyroid adenomas and primary hyperplasia--a difference that could prove useful in distinguishing these entities clinically. PMID- 3344019 TI - Neonatologists judge the "Baby Doe" regulations. AB - The federal regulations now in effect governing the treatment of severely handicapped infants--the so-called Baby Doe regulations--are based on the 1984 amendments to the Child Abuse Prevention and Treatment Act; these regulations require that, except under certain specified conditions, all newborns receive maximal life-prolonging treatment. We sent questionnaires to the 1007 members of the Perinatal Pediatrics Section of the American Academy of Pediatrics to determine their views on the Baby Doe regulations and on whether the regulations had affected their practices; 494 of the members (49 percent) responded. Of the respondents, 76 percent believed that the current regulations were not necessary to protect the rights of handicapped infants; 66 percent believed that the regulations interfered with parents' right to determine what course of action was in the best interest of their children; and 60 percent believed that the regulations did not allow adequate consideration of infants' suffering. In responding to the three hypothetical cases of severely handicapped newborns, up to 32 percent of the respondents said that maximal life-prolonging treatment was not in the best interests of the infants described but that the Baby Doe regulations required such treatment. The responding neonatologists' concerns about the current Baby Doe regulations were similar to those expressed by the United States Supreme Court in rejecting an earlier set of Baby Doe regulations. This similarity suggests that the current Baby Doe regulations should be reevaluated. PMID- 3344020 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 11-1988. A 44-year-old woman with prominent thrombocytosis. PMID- 3344021 TI - Genetic defects in primary hyperparathyroidism. PMID- 3344018 TI - Lack of relation of increased malformation rates in infants of diabetic mothers to glycemic control during organogenesis. AB - To determine how much insulin-dependent diabetes increases a woman's risk of giving birth to a malformed infant and how that risk is influenced by metabolic control, we followed 347 diabetic and 389 control women who enrolled in the study within 21 days of conception (the early-entry group) and 279 diabetic women who entered later (the late-entry group). We detected major malformations in the infants of 4.9 percent of the early-entry diabetic women, 2.1 percent of the controls, and 9.0 percent of the late-entry diabetic women. Malformation rates were significantly higher among offspring of early-entry diabetic women than among those of controls (odds ratio, 2.45; lower one-sided 95 percent confidence limit, 1.12; P = 0.027), and higher among late-entry than among early-entry diabetic women (odds ratio, 1.91; lower one-sided 95 percent confidence limit, 1.07; P = 0.032). Mean blood glucose and glycosylated hemoglobin levels during organogenesis were not significantly higher in women whose infants were malformed. Hypoglycemia (glucose, less than or equal to 50 mg per deciliter [2.8 mmol per liter]) was not significantly more common in the same group. Hyperglycemia and glycosylated hemoglobin were not correlated with malformation. The data suggest that more sensitive measures are needed to identify the teratogenic mechanisms, or that not all malformation can be prevented by good glycemic control. Despite the increased malformation rate among infants of the early-entry diabetic women, as compared with the controls, the more favorable outcome seen in the former group as compared with the late-entry group justifies the attempt to achieve good metabolic control around the time of conception. PMID- 3344022 TI - Immunosuppression for insulin-dependent diabetes. PMID- 3344023 TI - The impact of televised movies about suicide. PMID- 3344024 TI - Can you "run your heart out"? PMID- 3344025 TI - Streptokinase and ejection fraction after myocardial infarction. PMID- 3344026 TI - Ketoconazole as an inhibitor of steroid production. PMID- 3344027 TI - Persistent hiccup cured by amantadine. PMID- 3344029 TI - On nursing. PMID- 3344028 TI - A rare case of hiccups. PMID- 3344030 TI - Self-application of the Heimlich maneuver. PMID- 3344031 TI - Molecular and cellular events during the germination of conidia of Sporothrix schenckii. AB - Hyaline, non pigmented microconidia of Sporothrix schenckii were harvested and allowed to form germ tubes in a basal medium with glucose at pH 4.0 and 25 degrees C. These conditions supported only the development of the mycelial form of Sporothrix schenckii in a reproducible, synchronized manner which allowed further analysis of the early cellular events occurring during the germination of the conidia. The relationship between macro-molecular synthesis (DNA, RNA and protein synthesis) and nuclear division, hyphal growth and septum formation were established. Following inoculation, protein synthesis was observed after 10 minutes followed by RNA synthesis, after 1 h and DNA synthesis after 2 h. The first nuclear division was observed during the 9 to 12 h interval after inoculation. Germ tube formation slightly preceeded nuclear division and was first evidenced 9 h after the induction of germination but was not completed until 12 h after inoculation. Septation was first observed in the germ tubes 0.25 micron from the mother cell-germ tube function 9 h after induction of germination. PMID- 3344032 TI - Ringworm infections in the nomadic Fulani of Nigeria, with particular reference to favus. PMID- 3344033 TI - An infection of cow with Mortierella wolfii. AB - A Japanese black cow from a farm in Gunma prefecture showed pyrexia, anorexia and depression. An autopsy revealed hepatic lesions consisting of numerous approximately spherical pale lesions scattered about on the surface and cut parts. The inflammatory lesions were observed in the right lobe of the lung. A part of the trachea was whitish and thickened. Histologically, necrotic foci were observed throughout most of the liver with fungal proliferation about the blood vessels. The lesions of the lung were seriously exudative and the fungus was also present in some of the bronchiole and on bloodvessel walls. Mortierella wolfii was isolated from the liver. The hyphae in the liver were identical in appearance with those seen in the tissues of rabbits experimentally inoculated with M. wolfii. This report is the first case of M. wolfii infection in Japan. PMID- 3344034 TI - US budget does well by big science in 1989 proposal to Congress. PMID- 3344035 TI - Army renews controversial plans for biological warfare laboratory. PMID- 3344037 TI - Ministers act to reduce industrial accidents. PMID- 3344036 TI - AIDS envelope protein patent. PMID- 3344038 TI - New rules for carcinogens. PMID- 3344039 TI - HIV infection in heterosexuals. PMID- 3344040 TI - Neural networks: learning from a computer cat. PMID- 3344042 TI - Not just cachectin involved in toxic shock. PMID- 3344041 TI - Blood transfusions and HIV vaccinations. PMID- 3344043 TI - Tay-Sachs carriers and tuberculosis resistance. PMID- 3344044 TI - A back-propagation programmed network that simulates response properties of a subset of posterior parietal neurons. AB - Neurons in area 7a of the posterior parietal cortex of monkeys respond to both the retinal location of a visual stimulus and the position of the eyes and by combining these signals represent the spatial location of external objects. A neural network model, programmed using back-propagation learning, can decode this spatial information from area 7a neurons and accounts for their observed response properties. PMID- 3344045 TI - Interrelationships among primate higher taxa. AB - One of the most controversial issues in primate palaeontology concerns the phylogenetic position of the extinct primate infraorder Adapiformes. During the Eocene, this group of primates of modern aspect possessed a holarctic distribution, and may have been present in the poorly known Palaeogene of Africa. Mainly on the basis of craniodental morphology, at least four hypotheses have been proposed concerning the phylogenetic interrelationships among adapiforms and other primate higher taxa: (1) that adapiforms are ancestral to both lemuriforms (including Lorisoidea) and anthropoids; (2) that adapiforms cannot be shown to possess a special phylogenetic relationship with either lemuriforms or anthropoids; (3) that adapiforms are the sister taxon of lemuriforms; and (4) that Adapiformes is not a natural, monophyletic group, but rather consists of nested clades within the radiation of lemuriforms. Here, we describe features of the ankle and wrist joints of several adapiform taxa that provide an independent test of the preceding hypotheses. These traits suggest that lemuriforms are monophyletic with respect to known adapiforms, but that adapiforms nevertheless are their stem lineage (sensu Ax). PMID- 3344046 TI - Primary genetic control of somatic sexual differentiation in a mammal. AB - The classical view of mammalian sexual differentiation is that a gene on the Y chromosome transforms the indifferent gonad into a testis. The Leydig cells then secrete androgen which stimulates the development of the male reproductive tract, and the Sertoli cells secrete Mullerian inhibitory substance which inhibits the development of the female reproductive tract. In the absence of a testis, the Mullerian duct develops into the Fallopian tubes, uterus and vagina. Thus the whole of sexual differentiation is thought to be hormonally mediated as a consequence of this initial genetic determination of gonadal sex. We have found evidence in a marsupial mammal for extensive sexual dimorphisms which precede any morphological differentiation of the gonads. Thus the classical view of mammalian sexual differentiation may have over-emphasized the role of testicular hormones, and overlooked earlier genetic effects. PMID- 3344047 TI - Structure of the liganded T state of haemoglobin identifies the origin of cooperative oxygen binding. AB - A molecular description of haemoglobin's cooperative oxygen binding and release was founded on the X-ray crystal structures of the deoxy-T and oxy-R states. Since the R state's oxygen affinity is close to that of an isolated subunit, the crucial allosteric phenomena are (1) the reduced affinity of the T state and (2) the kinetic pathway between the two quaternary structures. To investigate these phenomena directly, we have determined at high resolution (dmin = 2.1 A) the crystal structures of two liganded T-state haemoglobins. In the liganded T-state alpha subunit, both the tight packing of the haem and the intersubunit contacts inhibit a conformational change between the F helix and FG corner which would allow the haem to become planar and the iron to assume symmetrical R-like coordination. In the beta subunit, by contrast, we find no strain on the proximal side, but the intersubunit contacts prevent the haem from tilting about an axis parallel to the F helix which would open up the binding site to oxygen. In both subunits, ligand binding in the T state induces structural changes towards the tertiary conformation of the R state. PMID- 3344048 TI - Fluorometric calcium measurement. AB - Measuring the fluorescence of dyes specific for calcium and other cations allows the elucidation of cellular mechanisms such as neurotransmission, muscle contraction and cardiovascular regulation. PMID- 3344049 TI - Effects of an oral protein load on glomerular filtration rate in healthy controls and nephrotic patients. AB - Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and humoral factors were simultaneously examined before and after a 50-gram oral protein load in 12 healthy controls and 12 nephrotic patients. The protein load led to rises in GFR with unchanged filtration fraction in both groups although the rate of increase in GFR was greater in the former. The levels of blood urea nitrogen, serum osmotic pressure, plasma glucagon and serum insulin, but not plasma angiotensin II, were significantly elevated following the protein load. The increase in GFR after the protein load appears to be mainly caused by increased ERPF and afferent arteriolar vasodilation. PMID- 3344051 TI - Acute renal failure without fibrotic skin changes in progressive systemic sclerosis. AB - Scleroderma renal crisis (SRC) is defined as sudden development of accelerated hypertension, hyperreninemia, and acute renal failure in a patient with progressive systemic sclerosis (PSS). Although the diagnosis of PSS is generally straightforward because of dermal fibrosis, we report 2 patients who had PSS with SRC without the characteristic fibrotic skin changes of scleroderma. PSS should be considered in the differential diagnosis of unexplained acute renal failure and accelerated hypertension even though the cutaneous fibrotic manifestations of the disease may be absent. PMID- 3344050 TI - Renal excretion of purine bases. Effects of probenecid, benzbromarone and pyrazinamide. AB - Experiments were conducted which revealed the renal transport mechanism(s) of oxypurines by employing uricosuric agents and pyrazinamide. All specimens being drawn from healthy, normal subjects, the data showed that probenecid increased fractional uric acid, fractional hypoxanthine and fractional xanthine clearance, 3.97-, 1.52- and 2.31-fold, respectively, while benzbromarone increased fractional uric acid clearance 2.11-fold, decreased fractional xanthine clearance 0.48-fold and had no effect on fractional hypoxanthine clearance. In addition, pyrazinamide decreased both fractional uric acid clearance 0.35-fold and fractional xanthine clearance 0.44-fold but increased fractional hypoxanthine clearance 1.49-fold. These results suggest the possibility of differing renal transport mechanisms among the purine bases, uric acid, hypoxanthine and xanthine. PMID- 3344052 TI - Patchy renal vasoconstriction in rhabdomyolysis-related acute renal failure. AB - In rhabdomyolysis-related acute renal failure evidence of patchy renal vasoconstriction during the recovery phase was obtained by abdominal CT scan, which showed a wedge-shaped high-density area in the kidney. PMID- 3344053 TI - Immune-mediated glomerulonephritis after exposure to paraquat. AB - Exposure to paraquat was followed 1 week later by mild respiratory distress in a previously healthy farmer who developed a mixed nephrotic/nephritic syndrome 3 months later. Percutaneous renal biopsy showed endo-extra-capillary proliferative glomerulonephritis associated with a linear pattern of IgG deposits along the glomerular capillary wall. This is the first case report of an association between exposure to a low dose of paraquat (as suggested by the mildness of the respiratory symptoms) and development of glomerulonephritis, possibly related to the occurrence of anti-glomerular basement membrane antibodies. The possibility is suggested that immune-mediated mechanisms of glomerular damage may be triggered by exposure to low-dose paraquat. PMID- 3344054 TI - Effect of ciclosporin on active Heymann nephritis. AB - The effects of ciclosporin on active Heymann's nephritis starting at different times after induction was studied. When given at the time of antigen injection, ciclosporin blocked both free antibody and circulating immune complex formation. Immunopathology and renal function tests remained normal in this group despite a rise in both these parameters to control values after ciclosporin was discontinued. When given at a later stage of the disease process, despite suppression of both antibody and complex formation, neither pathology nor functional parameters were modified. This suggests either a limited time frame for immunologically mediated injury in Heymann's nephritis or that early treatment with ciclosporin may permanently alter a vital primary step in the immunopathogenesis. PMID- 3344055 TI - Reduction of urea generation and muscle protein degradation by adrenalectomy in acutely uremic rats. AB - The effect of adrenalectomy on the enhanced protein degradation in acute uremia was investigated. Therefore, serum urea nitrogen, urea N appearance and Nt methylhistidine were followed in bilaterally nephrectomized rats. At 48 h after induction of uremia the animals displayed serum urea nitrogen levels of 223 +/- 9.5 mg/dl as compared to 26.0 +/- 1.0 mg/dl in sham-treated rats. This increment was significantly attenuated in acutely uremic, adrenalectomized animals (176 +/- 6.0 mg/dl). When these rats were substituted with corticosterone (5 mg/kg body weight), serum urea nitrogen readily increased to levels of acutely uremic animals with intact adrenal glands (225 +/- 6.0 mg/dl). The net generation of urea, as determined by the urea N appearance, was significantly increased during acute uremia (370 +/- 26 mg/48 h) as compared to SHAM animals (220 +/- 15 mg/48 h). This increment of urea formation could almost be completely reversed by simultaneous adrenalectomy (238 +/- 20 mg/48 h). When these rats were substituted with corticosterone, the urea N appearance rebounded to values quite comparable to acutely uremic rats with intact adrenal glands (363 +/- 30 mg/48 h). To determine whether skeletal muscle proteins might serve as a source for the enhanced protein degradation in acute uremia, plasma levels of Nt-methylhistidine were measured. Bilaterally nephrectomized rats had Nt-methylhistidine values of 9.6 +/- 1.0 micrograms/ml. In acutely uremic rats without adrenal glands, Nt methylhistidine levels were found to be significantly decreased (6.0 +/- 0.4 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344056 TI - Effect of some uremic toxins on oxygen consumption of rats in vivo and in vitro. AB - In rats, oxygen consumption is reduced by about 40-50% 24 h after bilateral nephrectomy. This is also the case when the animals are pretreated with triiodothyronine, 3 x 0.75 mg/kg body weight orally, for 2-3 days. Indole, cresol, putrescine, methylguanidine or acetoine was given intraperitoneally to normal rats at doses of between 5 and 300 mg/kg body weight. Only low single doses of indole (5 mg/kg) reduced oxygen consumption significantly. Single doses of the other substances studied were ineffective even at tenfold higher doses. Some combinations of these substances, however, (10 mg/kg each), reduced the metabolic rate significantly. In contrast to the results in vivo, plasma of uremic rats, as well as the uremic toxins, dissolved in Krebs-phosphate buffer pH 7.4 at concentrations of 30 mg/dl each, had no influence on respiration of rat diaphragma or liver slices in vitro (single substances and different combinations). PMID- 3344057 TI - Reporting laboratory values in patients on chronic dialysis. PMID- 3344058 TI - Urinary excretion rate of guanidinoacetic acid in essential hypertension. PMID- 3344059 TI - IgA nephropathy in rheumatoid arthritis. PMID- 3344060 TI - Red blood cell electric charge and microalbuminuria in diabetes mellitus. PMID- 3344061 TI - Glomerulocystic kidney in a patient affected with progressive systemic sclerosis. PMID- 3344062 TI - Plasma levels of heparin cofactor II in nephrotic syndrome of children. PMID- 3344063 TI - Antiglucocorticoid RU 38486 attenuates retention of a behaviour and disinhibits the hypothalamic-pituitary adrenal axis at different brain sites. AB - Adrenalectomized rats displayed a deficiency in retention of an immobility response acquired during an initial 15-min forced swimming procedure (Porsolt swimming test) and measured 24 h later in a 5-min retest session. The deficit could be restored dose dependently with the glucocorticoid dexamethasone (microgram range) administered 15 min after the initial test. The antiglucocorticoid RU 38486 administered subcutaneously (1 and 10 mg/kg) inhibited the dexamethasone effect and caused a parallel shift in the dose response curve of dexamethasone. Intracerebroventricular administration of RU 38486 to intact rats immediately before the initial test attenuated retention of acquired immobility over a 100,000-fold lower dose range (ng) and increased the plasma corticosterone level. Local administration of 1 ng RU 38486 in the dentate gyrus of the hippocampus also diminished the percentage immobility, but did not influence the adrenocortical response. Injections of RU 38486 in parafascicular and paraventricular nucleus were ineffective on behaviour. In the latter nucleus the antiglucocorticoid disinhibited the activity of the hypothalamus-pituitary adrenal axis. Intracerebroventricular pretreatment with promegestone did not interfere with RU 38486 action, ruling out involvement of its antiprogestin properties. Intracerebroventricular or subcutaneous treatment of intact rats with the antimineralocorticoid RU 28318 was not effective. Finally, adrenalectomized rats replaced with corticosterone delivered via subcutaneously implanted 100-mg corticosterone pellets showed normal behavioural performance, while a 25-mg implant did not. The present study with local infusions of RU 38486 indicates that glucocorticoid feedback via type 2 receptors exerts a long-term influence on behaviour in the hippocampus and controls the activity of the hypothalamus pituitary-adrenal axis in the paraventricular nucleus. PMID- 3344065 TI - Plasma prolactin and luteinizing hormone profiles during the estrous cycle of the female rat: effects of surgically induced persistent estrus. AB - Experiments were carried out to investigate the hypothalamic control mechanism for prolactin (PRL) and luteinizing hormone (LH) secretion in the female rat. Anterior medial preoptic nucleus (AMPO) or suprachiasmatic nucleus (SCN) lesions were produced by passing 5-10 microA of direct current (tip negative). Persistent estrus (PE) began as early as 6 days and as late as 30 days after electrolytic lesioning. Blood samples obtained during diestrus, proestrus and estrus revealed well-described profiles of plasma PRL and LH in sham-lesioned animals, indicating that our cannulation and blood sampling procedure had no adverse effects on the plasma hormone levels. Individual sham-operated animals sampled on successive or alternate proestrous afternoons showed precise timing of the PRL and LH surges. However, when a shift occurred in the PRL surge a comparable shift would also occur in the LH surge, indicating a coupling between the mechanisms regulating the PRL and the LH surge. The AMPO-, SCN- or combine-lesioned PE animals exhibited low basal levels of plasma PRL and LH. Small secretory bursts occurred one to three times during the 6-hour sampling periods. Animals with incomplete SCN lesions had plasma PRL titers significantly higher than the other 3 groups. Plasma progesterone levels were significantly lower in the PE animals (p less than 0.01), whereas plasma estrogen levels were not significantly different from proestrous controls. These experiments indicate that during the afternoon of proestrus, the surges of plasma PRL and LH are very precise in the time of onset. Moreover, the mechanisms controlling the surge of PRL and LH are temporally coupled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344064 TI - Immunocytochemical and biochemical characterization of angiotensin I and II in cultured neuronal and glial cells from rat brain. AB - Neuronal and glial cells cultured from neonatal rat brains showed staining for both angiotensin I and II using the peroxidase-antiperoxidase method. In glial cell extracts of normotensive Wistar-Kyoto rats, the concentrations of angiotensin I and II were 12.47 +/- 2.71 (n = 4) and 66.73 +/- 13.28 fmol/mg protein (n = 4). Angiotensin I and II found in neuronal cell extracts of normotensive Wistar-Kyoto rats were 11.29 +/- 2.99 (n = 4) and 60.25 +/- 12.77 fmol/mg protein (n = 4). No significant difference was found in the concentration of angiotensin I and II in both cell types from the same rat strain. Angiotensin I concentrations of 16.83 +/- 3.43 fmol/mg protein (n = 5) determined in neuronal cell extracts derived from spontaneously hypertensive rats did not differ significantly from those found in neuronal cell extracts of Wistar-Kyoto rats. However, neuronal cell extracts from spontaneously hypertensive rats revealed values of 25.19 +/- 4.31 fmol angiotensin II/mg protein (n = 4). This was significantly different (p less than 0.05) and represented a 58% reduction in the angiotensin II levels in neuronal cells from spontaneously hypertensive rats compared to Wistar-Kyoto rat cultures. Angiotensin I and II measured in the growth medium containing 10% plasma-derived horse serum was below the detection limit of both radioimmunoassays. No difference in the angiotensin I and II levels was found in cells kept in serum-free medium. The angiotensin I and II immunoreactive material determined in the cell extracts could be characterized on reversed-phase high pressure liquid chromatography as (Ile5)-angiotensin I and II. (Ile5)-angiotensin III was not detectable. PMID- 3344066 TI - Characterization of neurophysin in the anterior pituitary gland of sheep. AB - Portions of sheep anterior pituitary lobe tissue were extracted under acid conditions and assayed for the two neurophysins (oN-III and oN-I/II) by radioimmunoassay. In all tissues examined, oN-III and oN-I/II immunoreactivities were detected. Using a combination of isoelectric focusing and polyacrylamide gel electrophoresis, the neurophysins of the anterior pituitary gland behaved like oN III and oN-I/II. oN-III of the anterior pituitary was purified by affinity chromatography and high-performance liquid chromatography. This corticotroph oN possessed an amino acid analysis similar to that of oN-III and an N-terminal amino acid sequence, including residues 1-24, identical to that of authentic oN III. These findings support the work of others who have identified neurohypophysial hormones in the anterior pituitary gland. PMID- 3344067 TI - Bovine 'neurophysin II' stimulates growth hormone release in the estradiol-primed male rat. AB - Basal plasma concentrations of growth hormone (GH) were monitored in both normal and estradiol-primed male rats by the collection of sequential blood samples from freely moving rats, via chronic intraatrial cannulae. Blood was sampled every 2 min for a period of 80 min and plasma GH levels determined by radioimmunoassay. The normal male rats displayed a pulsatile release of GH, while the estradiol primed male rats exhibited a relatively steady level of plasma GH concentration. The rats exposed to high levels of estradiol (1.59 +/- 0.42 nmol/l plasma) also had a higher mean value of basal GH concentration. An injection of 100 micrograms/kg of bovine neurophysin II did not alter GH release in the normal male rats. However, it did significantly elevate GH levels in the estradiol primed animals to a mean peak level approximately six times the mean basal level. The administration of 100 micrograms/kg of bovine neurophysin I to estradiol primed male rats did not produce any change in plasma GH levels and thus eliminates the possibility of the nonspecific stimulation of neurophysin II on GH release. PMID- 3344068 TI - Comparison of spinal needles, epidural catheters, and cordis lumbar catheters for intraoperative removal of cerebrospinal fluid. AB - The present study was designed to determine whether the Cordis lumbar catheter is more effective than spinal needles or epidural catheters for intraoperative removal of cerebrospinal fluid (CSF). We also sought to determine whether placing two spinal needles, two epidural catheters, or two Cordis CSF catheters per patient provides more effective removal of CSF than placing one such CSF drain. Spinal needles were associated with a higher incidence of fresh blood in the CSF when CSF removal was desired, a lower incidence of adequate volume of CSF drainage, and a higher incidence of the need to reposition needles to continue CSF removal. Epidural catheters were associated with a lower incidence of adequate rate of CSF drainage. The slow rate of CSF drainage with epidural catheters was clinically important because it impaired operative conditions, delayed surgical progress, or both. Cordis CSF catheters took longer to place than spinal needles or epidural catheters. This time difference (about 3 minutes for one CSF catheter and 6 minutes for two) was statistically significant, but probably is not clinically important. The results were similar whether one or two CSF drains were used per patient. It is concluded that Cordis CSF catheters are more effective than spinal needles or epidural catheters for intraoperative removal of CSF. Using two spinal needles, two epidural catheters, or two Cordis CSF catheters per patient did not provide better CSF removal than using one such drain. PMID- 3344069 TI - Atypical epidermoid cyst of the brain. AB - A patient with an epidermoid cyst of the brain was erroneously diagnosed as having a meningioma on computed tomography. This case highlights some of the problems of interpretation and fluid/solid characterization with computed tomography. PMID- 3344070 TI - Choroidal epithelial cyst of the prepontine region: case report and ultrastructural study. AB - A case of choroidal epithelial cyst of the prepontine region is reported. The cyst wall was studied using light and electron microscopy. Electron microscopy revealed that the lining of the cyst consisted of a single layer of epithelial cells resting on a basement membrane. The epithelial cells contained numerous club-shaped microvilli and occasional cilia. There were no coating materials on the surface of the microvilli. Tight junctions and interdigitations were present between contiguous cells. The blood vessels were fenestrated. These ultrastructural findings suggest that the epithelial cyst was derived from the choroidal epithelium rather than ependyma or endodermal tissue. PMID- 3344071 TI - Triad of hypopituitarism, granulomatous hypophysitis, and ruptured Rathke's cleft cyst. AB - A 19-year-old girl with pituitary insufficiency and a large sella turcica was found to have granulomatous hypophysitis in association with a Rathke's cleft cyst. We think that the inflammatory process represents a foreign body reaction to leakage of cyst contents, with destruction of pituitary tissue. PMID- 3344072 TI - Pseudoankylosis of the mandible after temporal bone attached craniotomy. AB - Mandibular hypomobility after intracranial surgical procedures is seldom encountered. A case of limited oral opening after temporal bone attached craniotomy is described. The condition is due to fibrosis of the temporalis muscle resulting in a pseudoankylosis of the temporomandibular joint. The appropriate operative intervention is transoral coronoidectomy, which restores normal joint function. PMID- 3344073 TI - Somatosensory evoked potential monitoring accurately predicts hemi-spinal cord damage: a case report. AB - Separate somatosensory evoked potentials (SEPs) were monitored from each lower extremity during instrumentation for a spinal fracture. The SEP disappeared from the right lower extremity after instrumentation, but not from the left lower extremity. The predicted hemi-spinal cord injury was pathologically confirmed. The merits of sequential, as opposed to simultaneous, stimulation of multiple extremities during surgical monitoring are discussed. PMID- 3344074 TI - Cavernomas of the spinal cord: report of two cases. AB - Two cases of intramedullary cavernomas are presented. Both patients showed progressive neurological deficit. Cavernoma must be considered in the differential diagnosis of spinal cord tumors. PMID- 3344075 TI - Acute cervical spondylytic myelopathy. AB - Myelopathy is a common consequence of cervical spondylosis. Typically, the syndrome develops gradually over a long period. Rapidly progressive deterioration in the absence of trauma or other precipitating factors is exceptional. We report a case of a rapidly progressive acute myelopathy secondary to cervical spondylosis without identifiable precipitating cause. The importance of recognizing this syndrome lies in the fact that rapid operative intervention may result in significant neurological recovery. The value of magnetic resonance imaging preoperatively and postoperatively is emphasized. PMID- 3344076 TI - Enteral and intranasal treatment for vasopressor-dependent hypotension in C1 tetraplegia. AB - A complete traumatic C1 spinal cord lesion leads to bradycardia and temporary hypotension until fluid administration can restore blood volume and pressure to the autosympathectomized capacitance vessels. In spite of adequate volume status, however, our patient required intravenous pressor agents to maintain adequate arterial and central venous pressure several weeks after injury. Using oral pseudoephedrine and occasional nasal phenylephrine, intravenous lines could be removed with maintenance of arterial pressure and resolution of bradycardia. PMID- 3344077 TI - Subarachnoid hemorrhage and "normal pressure hydrocephalus": fatal complication of percutaneous microcompression of the gasserian ganglion. Case report. AB - A 62-year-old man underwent percutaneous balloon catheter compression of the gasserian ganglion for typical trigeminal neuralgia. After this, a subarachnoid hemorrhage was discovered and normal pressure hydrocephalus developed, which required shunting. Although the neurological function recovered, the patient died 8 months later because of supervening hepatic insufficiency, probably caused by protracted antibiotic therapy. Such a fatal complication, the first one associated with the technique of percutaneous trigeminal compression, was perhaps predisposed by preexistent cerebral atrophy with enlargement of the subarachnoid spaces; the unforeseen piercing of the dilated trigeminal cistern probably permitted the intracranial subarachnoid diffusion of an otherwise trivial hemorrhage. The safety of the procedure may be greatly reduced in such instances. PMID- 3344079 TI - Carotid-cavernous fistula caused by BB air rifle. PMID- 3344078 TI - Acute subdural hematoma from ruptured posterior communicating artery aneurysm. AB - Acute spontaneous subdural hematoma is infrequent in association with rupture of intracranial saccular aneurysm. In the majority of cases, aneurysms of the middle cerebral artery along the convexity or of the anterior cerebral artery along the interhemispheric fissure are found to be the culprits. We present two recent cases of internal carotid-posterior communicating artery aneurysms causing acute subdural hematoma with little or no subarachnoid hemorrhage and discuss the possible mechanisms for this occurrence. PMID- 3344080 TI - Intravascular volume expansion affecting blood flow. PMID- 3344081 TI - Sciatica and epidural gas. PMID- 3344082 TI - Syringomyelia and hydromyelia. PMID- 3344083 TI - Electromagnetic field focusing system in the treatment of brain tumors. AB - The electromagnetic field focusing (EFF) probe, which is based on the principle of eddy current convergence, produces intense pinpoint heat at its point of contact with tissue. This allows cutting and vaporization of tissue and coagulation of vessels. The present experiments were conducted to study heat distribution to the surrounding tissue in brain and phantom and the effect on the brain of vaporization of intracerebral tumors in 19 rabbits. The follow-up period was as long as 47 days. The heating pattern showed a rise of temperature up to 250 degrees C at the probe tip, with minimal or no temperature increase at 2 mm and beyond. Minimal or no change was noted in the surrounding brain after tumor vaporization, indicating that this system would be safe in the vaporization of brain tumors in clinical neurosurgery. PMID- 3344084 TI - Capillary permeability and boron distribution in ethylnitrosourea-induced rat glioma. AB - The vasculature and capillary permeability of gliomas induced by ethylnitrosourea in Sprague-Dawley rats were studied with horseradish peroxidase and Evans blue dye. The distribution of the boron-10 compound, Na2(10)B12H11SH, which is now in clinical use for boron neutron capture therapy (BNCT) for brain tumors, was investigated quantitatively using neutron-induced alpha-autoradiography. The vasculature and the degree of capillary permeability varied widely, depending mainly on the size of the glioma, and were often heterogeneous even in the same tumor. The distribution of boron-10 also varied, correlating to capillary permeability. The boron-10 concentration and the tumor:blood concentration ratio in large and medium-sized gliomas were adequate for successful BNCT. This study suggests that the vasculature and capillary permeability of the target brain tumor exert an important influence on the therapeutic efficacy of BNCT. PMID- 3344085 TI - Microsurgical treatment of ventral (paraclinoid) internal carotid artery aneurysms. AB - Eight cases of ventral (paraclinoid) internal carotid artery aneurysms are presented. These aneurysms often challenge the surgeon because (a) they are partially or completely obscured by the optic nerve, internal carotid artery, and anterior clinoid process; (b) there is no proximal internal carotid artery control intracranially; and (c) part of the neck and fundus of the aneurysm is located within the cavernous sinus. These aneurysms, which have been classified as separate from the typical carotid-ophthalmic aneurysm group, are illustrated, and their surgical treatment and problems described. PMID- 3344086 TI - Recording and measuring the interior features of intracranial aneurysms removed at autopsy: method and initial findings. AB - Among the factors that determine the behavior of an intracranial aneurysm is the relationship between its volume and the size of the orifice. The investigative method described herein is the means being used to define that relationship in humans. It is a postmortem study that focuses on unruptured aneurysms. Central to the protocol was a synthetic rubber cast of the aneurysm's interior. The cast was made under normal arterial pressure so that unruptured aneurysms were reexpanded to lifelike size and shape. After the cast was removed intact from the specimen, the lumenal features recorded upon it were verified by comparison with the opened aneurysm. Working now only with the cast, the chamber was cut from the artery through its neck. The orifice area was determined by dividing it, mathematically, into many smaller, measurable forms. Chamber volume was ascertained by a fluid displacement technique. Both measurements were made with magnification and engineering instruments. Casts of ruptured or thrombosed aneurysms gave helpful morphological information, but were of limited value for measurement. The techniques are described, and examples of the initial results are presented. PMID- 3344087 TI - Models of spinal cord injury: Part 3. Dynamic load technique. AB - Having previously studied a static load model of cord injury in rats, we report here an evaluation of a dynamic (weight drop) technique. Under general anesthesia, Sprague-Dawley rats were subjected to a laminectomy at T12, after which a 10-g weight was dropped onto a force transducer and impounder resting on the spinal cord; the weight drop distances varied in different groups from 0 (control) in increments of 2.5 cm to a maximal height of 17.5 cm. A strain gauge attached to the force transducer yielded an oscilloscopic wave form from which force of impact (peak force and impulse) was calculated. Eighty-six animals were used in this parametric study. The animals were observed for 4 weeks postinjury with two tests of motor recovery (Tarlov score for locomotion and the inclined plane test). After sacrifice at 4 weeks, the spinal cords were removed and, with the use of preset criteria, qualitative histopathological scoring of the extent of tissue damage was carried out. We found that the variable height of weight drop was capable of producing a graded injury that correlated with the force of injury (as measured by the force transducer) and with the outcome parameters of functional recovery and degree of morphological damage in the spinal cord. Histopathologically, there was a tendency to central cavitation of the cord. Both the static load and the dynamic load techniques seem to be valid models of spinal cord injury. Pathologically, however, the tissue damage after static load injury involved primarily the dorsal half of the cord. By contrast, the dynamic load technique produced central cavitation comparable to that observed in human spinal cord injury. In this respect, the dynamic model seems to be superior and its use is therefore recommended for studies of therapeutic intervention for spinal cord injury. PMID- 3344088 TI - Experimental spinal cord injury: effect of a calcium channel antagonist (nicardipine). AB - Variable benefits from the use of a number of calcium channel blockers in experimental spinal cord injury have been reported. To our knowledge, these agents have not been previously tested in a contusion model of cord injury in which neurological outcome is one of the critical outcome parameters. We carried out preliminary behavioral toxicity testing to identify a range of low, moderate, and high dosage levels of the calcium channel blocker, nicardipine; these dosage levels were to be used subsequently in formal testing. After laminectomy at T8 under general anesthesia in rats, a 10-g weight was dropped from a height of 5 cm onto the spinal cord. The animals were randomly assigned to four groups: control or one of three nicardipine treatment groups: (a) low dose (1 mg/kg, followed by a continuous 23-hour infusion of 0.5 mg/kg/hour), (b) moderate dose (10 mg/kg, followed by 5 mg/kg/hour for 23 hours, and (c) high dose (20 mg/kg, followed by 23-hour infusion of 10 mg/kg/hour). Functional recovery was tested over the course of 4 weeks with the Tarlov scale, the inclined plane, and a sensory-motor battery of tests (combined behavioral score). After sacrifice at 4 weeks, morphometric analysis of residual gray and white matter was performed at the epicenter of the spinal cord injury. Statistical analysis of the behavioral data failed to reveal any differences among the control or nicardipine treatment groups. The morphometric analysis similarly failed to show differences between the control and any treatment group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344089 TI - New subtype of acute odontoid fractures (type IIA). AB - A new subtype of axis fracture, thought to be a variant of the Type II odontoid fracture, is described. High resolution, thin section computed tomography can assist in the identification of comminuted fractures at the base of the dens with associated free fracture fragments. Because these injuries are markedly unstable and cannot be suitably realigned and reduced by external means, early surgical therapy should be considered. PMID- 3344091 TI - Experience with limited versus extensive disc removal in patients undergoing microsurgical operations for ruptured lumbar discs. AB - Of 68 patients undergoing microsurgical operations for ruptured lumbar discs, 33 were treated by removing only the herniated fragments. In the remaining 35, an attempt was made to remove the entire disc. No recurrences followed the more extensive discectomies during follow-up periods varying from 11 to 30 months. Seven recurrences followed operations in which only the offending fragment was removed (recurrence rate of 21%), four within 6 months. Among 68 patients treated by conventional neurosurgical techniques, there was only one recurrence during follow-up periods of at least 4 years. None of the operations was clearly superior in relieving leg pain, but microsurgically treated patients spent less time in the hospital and returned to work more quickly. PMID- 3344090 TI - Tonsillar herniation on magnetic resonance imaging. AB - To evaluate the risk of tonsillar herniation, the caudal pole of the cerebellar tonsil in posterior fossa mass lesions and anomalies was investigated with magnetic resonance imaging. The cerebellar tonsil was clearly demonstrated in relation to the surrounding structures on T1-weighted images in the paramedian or midline sagittal plane. In 78% of a control group of 50 cases, the tonsil was located just on or close to the upper border of the posterior lip of the foramen magnum. It was close to the line of the foramen magnum in 4 cases (8%), but displacement below this line was not observed in any case. In 18 cases of posterior fossa mass lesions, the tonsil tended to be in a lower position than in the control group, and tonsillar displacement below the foramen magnum was noted in 3 cases. Two of these cases had anterior medullary displacement with loss of the cerebrospinal fluid (CSF) space anterior to the tonsil; these patients had either rapid clinical deterioration or severe papilledema. In the remaining case and in 3 additional cases of Chiari malformation, the tonsils were displaced into the cervical canal with preservation of the CSF space, and the patients showed no signs of rapid clinical deterioration or increased intracranial pressure. The present study suggests that tonsillar displacement through the foramen magnum with associated anterior medullary displacement and loss of the CSF space anterior to the tonsil can be regarded as a sign of tonsillar herniation. PMID- 3344092 TI - Monoamine alterations during experimental hydrocephalus in neonatal rats. AB - The present study was designed to determine the selected monoamine changes that occur during infantile hydrocephalus. Obstructive hydrocephalus was induced in newborn rats by injection of a suspension of kaolin into the 4th ventricle and cisterna magna. Eleven days later, experimental animals and their sham-operated littermate controls were killed and pieces of frontoparietal cortex, neostriatum, cerebellar vermis, and brain stem were processed for high performance liquid chromatography. Grossly, the lateral ventricles were extremely enlarged, the cerebral cortex was thinned, the neostriatum was compressed, and portions of the tectum and cerebellum were vacuolated. Decreases in norepinephrine (71%), dopamine (73%), and serotonin (50%) were observed in the cerebral cortex, neostriatum, and cerebellum, respectively. Brain stem norepinephrine and serotonin were increased 70% and 50%, respectively. These increases may indicate impairment of axonal transport or damage to projections from the locus ceruleus and raphe region. These preliminary results suggest that infantile hydrocephalus causes perturbations in the levels of different monoamines in several brain regions. Such changes may critically influence neuronal function and development, as well as the therapeutic management of hydrocephalus. PMID- 3344094 TI - American Academy of Neurology. 40th annual meeting. Cincinnati, Ohio, April 17 23, 1988. Abstracts. PMID- 3344093 TI - Praziquantel (pyrazinoisoquinolone) in active cerebral cysticercosis. AB - A prospective open therapeutic study on volunteers with active neurocysticercosis using pyrazinoisoquinolone (Praziquantel) has shown that it is a safe and effective drug. Objective assessment of the effect of treatment was by high resolution sequential computed tomographic scanning. Sixty-six patients received the drug. Forty-one records were available for complete analysis at the end of 1 year of follow-up. The concomitant use of steroids reduced side effects significantly. A 98% improvement was achieved. PMID- 3344095 TI - Testicular feminization syndrome. AB - The testicular feminization syndrome occurs as a result of faculty genetic programming. This inherited condition causes an XY male embryo to develop into a person who has an XY karyotype and a female appearance. The described individual appears "female" at birth and is naturally socialized as a female. A testicular feminized "female" may seek routine health care at a primary health care center. Upon examination, certain identifying physical characteristics may be observed. Primary amenorrhea and infertility are inherent characteristics of the condition. This article describes the testicular feminization syndrome, its etiology/pathophysiology and both subjective and objective findings. Nursing interventions such as data collection, family tree charts, Barr body screening, education, referral and counseling are suggested. Nurse practitioners have the opportunity to identify suspected cases and direct those individuals toward appropriate treatment and discreet counseling. Counseling generally will emphasize that the TFS individual may consider herself female. PMID- 3344097 TI - Quality care in the Alaska bush. PMID- 3344096 TI - Enhancing sexual performance in COPD. AB - The fear of dyspnea and reduced exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) are often limiting factors in their participation in sexual activity. When the patient and health care practitioner approach sexual activity as any other physical activity, factors can be identified that promote sexual performance. Initial evaluation includes the patient's preferences, priorities and current physical capacity. The phases of sexual intercourse can be correlated with the energy requirements of other activities, such as walking or household tasks, to determine an individual's activity tolerance. Energy conservation techniques and breathing retraining can then be coordinated with sexual activity. In addition, cardiopulmonary reconditioning exercises are initiated to increase overall activity tolerance. Throughout this process, education is critical to assure the patient that well tolerated exercise may include dyspnea, and that dyspnea during sex is not more dangerous than during other well-tolerated exercise. PMID- 3344098 TI - Furazolidone is an alternative treatment for Giardia lambia. PMID- 3344099 TI - AIDS and the origin of species. PMID- 3344100 TI - The morality of hospital stewardship. PMID- 3344101 TI - Gastric ulcers. PMID- 3344102 TI - A seroepidemiologic profile of persons seeking anonymous HIV testing at alternate sites in upstate New York. PMID- 3344103 TI - Teaching about AIDS in public schools: characteristics of early adopter communities in Massachusetts. PMID- 3344104 TI - Barriers to the modification of sexual behavior among heterosexuals at risk for acquired immunodeficiency syndrome. PMID- 3344105 TI - The physician's patient-centered ethical imperative: implications, obligations, and problems. PMID- 3344106 TI - Is the human immunodeficiency virus really the initiator of human immunodeficiency? PMID- 3344107 TI - Systemic hypersensitivity reaction following a barium enema examination. PMID- 3344108 TI - Survey of injury prevention knowledge among low-income families. PMID- 3344109 TI - Epidemiologic study of choriocarcinoma. PMID- 3344110 TI - Rural doctors: need outweighs supply. PMID- 3344112 TI - Cancer in Ohio: keeping track. PMID- 3344111 TI - Cancer: a reawakening interest? PMID- 3344113 TI - "Mammography mania": is it sweeping the state? PMID- 3344114 TI - Transcutaneous cardiac pacemakers: recent advances. PMID- 3344115 TI - Treating your practice--III. Keeping in touch with your patients. OSMA Department of Communications and Physician Marketing. PMID- 3344116 TI - "An affair of the heart". PMID- 3344117 TI - Socialized medicine: the downfall of a free society. PMID- 3344118 TI - Interpreting tests--implications for cataract surgery. PMID- 3344119 TI - Management of nontraumatic vascular shunts involving the cavernous sinus. AB - The authors managed 38 consecutive cases of nontraumatic vascular shunts involving the cavernous sinus. Selective angiography demonstrated 12 carotid cavernous fistulas (CCFs) and 26 dural arteriovenous shunts (DAVSs). Visual disability occurred from glaucoma, venous retinopathy, optic neuropathy, or diplopia. Ten patients with slow-flow shunts and minimal dysfunction were treated medically to lower intraocular pressure (IOP) and/or instructed in manual compression of the internal carotid artery, ipsilateral to the lesion, using the contralateral hand. Percutaneous intraarterial embolization using detachable balloons, isobutylcyanoacrylate, or polyvinyl alcohol particles was successful in 16/18 DAVSs and 9/10 CCFs. The neuro-ophthalmic signs resolved in these 25 cases. Complications occurred in five patients. These included a transient hemiparesis, twelfth nerve palsy, unilateral nasal field loss, a pseudoaneurysm causing a third-nerve paresis, and temporary cavernous sinus thrombosis. Conservative therapy in mild cases and embolization in cases with visual disability or progressive signs are warranted. PMID- 3344120 TI - Treatment of optic neuritis with intravenous megadose corticosteroids. A consecutive series. AB - Twelve consecutive patients with optic neuritis of unknown etiology treated with 250 to 500 mg methylprednisolone every 6 hours are described. All patients improved, some dramatically and rapidly. Patients with swollen discs and visual loss for less than 6 weeks improved uniformly, rapidly, and completely. In some patients, progressive visual deterioration was reversed rapidly. Serum serologies and cerebrospinal fluids findings were of limited use in determining etiology or prognosis with treatment. Side effects included exacerbation of a preexisting psychosis, elevated glucose levels, and oral candidiasis. None required cessation of treatment. Patients with optic neuritis may benefit from intravenous megadose corticosteroids. PMID- 3344121 TI - The clinical appearance of the lamina cribrosa as a function of the extent of glaucomatous optic nerve damage. AB - The authors evaluated the shapes of the largest clinically visible pores on the surface of the lamina cribrosa in 87 eyes of 52 glaucoma patients and found an apparent progression in pore shape as a function of the extent of glaucomatous optic nerve head damage. Small, round pores predominated in eyes with mild field loss, oval pores were more common in eyes with moderate field loss, and striate or slit-shaped pores were most frequent in eyes with advanced field loss. If the pores of the lamina cribrosa elongate as a function of increasing glaucomatous optic atrophy, and if large pore size is associated with an increased risk for pressure-related axonal damage, then the threshold for ganglion cell atrophy may drop as the damage to the optic nerve progresses. PMID- 3344122 TI - Effect of visual blur on contrast sensitivity. Clinical implications. AB - Contrast sensitivity of normal subjects was measured under conditions of refractive blur that produced specific levels of visual acuity. Measurements were made at distance (with Vistech charts), at near (with Arden gratings), and with a pinhole to control pupil size. Under all conditions, when visual acuity was reduced by spherical lenses, there was a loss of contrast sensitivity over a broad range of spatial frequencies (i.e., not just at the higher frequencies that correlate with target letter size). By inference, it may be clinically hazardous to interpret contrast sensitivity results in patients with reduced acuity (from any cause) relative only to standard contrast sensitivity values based on subjects with normal visual acuity. If the potential effects of acuity are taken into account, contrast sensitivity testing can distinguish between deficits that are roughly equivalent to the loss of acuity and those which indicate more distinctive pathology of the media, retina, or optic nerve. PMID- 3344123 TI - New posteriorly located retinal breaks after pneumatic retinopexy. AB - Pneumatic retinopexy is a new procedure that is effective in treating many uncomplicated cases of rhegmatogenous retinal detachment (RD). It may be done in the office using a cryoprobe or laser and an expanding gas bubble and for this reason has become popular among RD surgeons. Reports of associated complications are limited. Three patients who had remarkably posterior retinal breaks after pneumatic retinopexy are presented with evidence that these breaks are a direct complication of this procedure. A possible explanation as to the pathogenesis of pneumatic retinopexy-associated posteriorly located retinal tears, as well as suggestions regarding prophylactic measures that may be taken to avoid this complication, are also presented. PMID- 3344124 TI - Cataract extraction after retinal detachment surgery. AB - Extracapsular cataract extraction (ECCE) was done in 31 eyes of 27 patients after previous retinal reattachment surgery with scleral buckling. A posterior chamber intraocular lens (IOL) was implanted in 21 eyes. No significant modifications in the cataract surgical technique were necessary. Final visual acuity was 20/40 or better in 26 eyes (84%). The complication rate was low. One patient was found to have a retinal detachment (RD) after cataract extraction that probably predated the cataract surgery. No recurrent retinal tears or detachment developed in any patients during an average 24-month follow-up period. PMID- 3344125 TI - Nanophthalmic sclera. Fibronectin studies. AB - The authors performed fibronectin studies on scleral specimens derived from a patient with nanophthalmos. Immunohistochemical staining with antifibronectin was conducted using both formaldehyde-fixed, paraffin-embedded tissue sections and unfixed tissue-cultured scleral cells. In each case, the nanophthalmic samples exhibited fibronectin staining stronger than that obtained from normal human subjects. Results from an enzyme-linked immunosorbent assay (ELISA) confirmed the histologic findings that, in tissue culture, the patient's scleral cells contained and secreted a higher amount of fibronectin than did the normal control cells. The elevated fibronectin level may be related to the development of nanophthalmos. PMID- 3344126 TI - Aneurysmal bone cyst of the orbit. AB - Proptosis of the left eye had developed in a 42-year-old woman for 2 months' duration. Roentgenogram studies showed a mass in the roof of the left orbit and bone erosion. An excisional biopsy confirmed the presence of an aneurysmal bone cyst. To the authors' knowledge, the patient is the oldest reported patient who has this uncommon orbital lesion. PMID- 3344127 TI - Temporal bone pathology associated with intracranial abscess. AB - Histological studies were performed on the temporal bones of 17 persons who died of intracranial abscess as a complication of chronic otitis media and mastoiditis. In all cases the route of intracranial infection was via the dura mater rather than through the labyrinth. During the acute stage of intracranial abscess formation, the site of intracranial invasion showed a destructive inflammatory reaction characterized by the presence of granulations, resorption and sequestration of bone, invasive cholesteatoma, collections of purulent exudate, and necrosis of dura mater. At this stage any attempt at definitive removal of diseased tissue would necessarily result in a larger dural defect at a time when local disease and systemic illness present unsuitable conditions for reparative procedures. For this reason it would seem prudent to limit early otologic surgery to ensuring adequate drainage (e.g., postauricular open-wound drainage) and to perform corrective surgery (e.g., tympanomastoidectomy with repair of the dural defect) after the intracranial abscess has been brought under control. PMID- 3344129 TI - Morphometric study of the growth of the subglottis after interruption of the circular structure of the cricoid. AB - In young rabbits the growth of the subglottis was studied over a period of 20 weeks after interruption of the circularity of the cricoid on the ventral side. In all cases the cricoid developed into a U-like structure which did not cause an airway narrowing. However, a cricoid lesion combined with an injury to the soft tissue lining led up to a subglottic stenosis. It was concluded that when the soft tissue layer is undamaged, an intact circular structure of the cricoid is not compulsory for the normal development of the subglottis. PMID- 3344128 TI - Effects of ototoxic diuretics (loop diuretics) on the endolymphatic sac. AB - The acute and chronic effects of treatment with ethacrynic acid (EA) and furosemide (FU) on the structure of the murine endolymphatic sac were studied by means of light and transmission electron microscopy. The animals were treated with loop diuretics in doses which are known to cause morphological alterations of the stria vascularis and a significant reduction of the endocochlear potential. A single intravenous injection of either EA or FU resulted in immediate morphological changes such as an increase in cytoplasmic contents of endoplasmic reticulum and more prominent Golgi structures of the light cells. These cells developed membrane-bound granules and a smooth tubular network in the apical cytoplasm. These findings together with the appearance of a precipitate on the luminal aspect of the cell membrane suggested secretory activity. Ten days after daily intraperitoneal injections with loop diuretics in subtoxic doses, the epithelial cytoarchitecture of the endolymphatic sac was altered, with pronounced veiling of the light cells by the dark cells. It is concluded that the changes in the endolymphatic sac epithelium after treatment with ototoxic diuretics may not be a result of a primary toxic effect on the sac per se, but rather be secondary to alterations in fluid and ion homeostasis in the rest of the inner ear. PMID- 3344130 TI - Vasculature of the crista ampullaris of the rat. PMID- 3344131 TI - [Intrauterine diagnosis of fetal measles infections and its risks]. PMID- 3344132 TI - [Interpretation of the English term "Caucasian"]. PMID- 3344133 TI - [Development of multiple renal cysts and their significance in the end stages of chronic renal insufficiency]. PMID- 3344134 TI - [Treatment of blepharospasm with botulinum A toxin injections]. PMID- 3344136 TI - [Early postnatal weight gain in low birth weight (less than or equal to 1500 g) premature infants]. PMID- 3344135 TI - [Air in the gastric wall]. PMID- 3344137 TI - [Rooming-in]. PMID- 3344138 TI - AIDS and cardiomyopathy. PMID- 3344139 TI - Medical jargon. PMID- 3344140 TI - Cotrel-Dubousset instrumentation. PMID- 3344141 TI - Nursing care of adolescents having posterior spinal fusion with Cotrel-Dubousset instrumentation. PMID- 3344143 TI - Rehabilitative aspects of nerve injuries of the hand. PMID- 3344142 TI - My life with scoliosis. PMID- 3344144 TI - Radiology Review. Secondary reflex sympathetic dystrophy. PMID- 3344145 TI - Fractures and the healing process (continuing education credit). PMID- 3344146 TI - Non-automotive vehicle injuries in adolescents. AB - After reviewing the data associated with injuries and deaths to adolescents participating in the activities described above, the question repeatedly arises: Why does our society continue to accept and promote this toll of injuries and deaths? While waiting for answers from researchers, physicians must continue an advocacy role for measures of protection known to reduce the morbidity and years of life lost among the adolescent age group. PMID- 3344147 TI - Adolescent drownings: swimming, boating, diving, and scuba accidents. PMID- 3344149 TI - Pediatric gastroenterology II. PMID- 3344148 TI - Initial management of minor acute soft-tissue injuries. PMID- 3344150 TI - What about infant pain? PMID- 3344151 TI - Cognitive development and children's perception of pain. PMID- 3344152 TI - Adolescent development and implications for pain management. PMID- 3344153 TI - Upper respiratory obstruction in the neonate: a case of neonatal rhinitis. PMID- 3344154 TI - Protecting our children through Kid Safe. PMID- 3344155 TI - Establishment of a hospital based children's sick room. PMID- 3344156 TI - Stressors in pediatric intensive care units. PMID- 3344157 TI - Pediatric management problems (neonatal conjunctivitis). PMID- 3344158 TI - Community assessment: the cornerstone of effective marketing. PMID- 3344159 TI - Common pediatric i.v. meds at a glance. PMID- 3344161 TI - Does membership in a support group alter needs of parents of chronically ill children? PMID- 3344160 TI - Anencephalic infants: should they be organ donors? PMID- 3344162 TI - Evaluations: an important managerial skill. PMID- 3344163 TI - Pain in children: comparison of assessment scales. PMID- 3344164 TI - Lung growth in rats subsequent to administration of intraperitoneal elastase during the first 4 weeks of life. AB - Male rats received intraperitoneal injections of porcine pancreatic elastase twice weekly during the first 4 weeks of life. Saline-injected male rats served as controls. After a 4-week recovery period, the rats were sacrificed, and the excised lungs were studied using saline- and air-filled volume-pressure curves, morphology, and biochemistry. Both air- and saline-filled volume-pressure curves showed loss of elastic recoil in the elastase-treated animals. In elastase treated animals the mean linear intercept was increased, the numbers of alveoli per unit area, per unit volume, and per lung decreased, and alveolar surface area decreased. These animals also showed a disproportionate increase of alveolar duct air at the expense of the proportion of alveolar air. Morphometric differences between the elastase-treated animals and the controls were somewhat smaller in this experiment than in a previous one in which the animals were sacrificed immediately after 4 weeks of intraperitoneal elastase. We attribute this difference to alveolar multiplication between 4 and 8 weeks of age. However, evidence is presented that these alveoli were abnormal. Loss of recoil properties was more evident after the 4-week recovery period than at the termination of elastase administration, suggesting that the newly formed alveoli were functionally abnormal. Collagen content was increased in the elastase group, but elastin was significantly decreased. This may be a good elastase model for assessing the hypothesis that lungs minimally damaged in infancy may have an increased susceptibility to environmental damage in later life. PMID- 3344166 TI - On complications of flexible bronchoscopy. PMID- 3344165 TI - Determination of airway hyper-reactivity in asthmatic children: a comparison among exercise, nebulized water, and histamine challenge. AB - An easy and accurate method of assessing bronchial hyper-reactivity could be of great value in identifying and classifying the degree of severity of asthma in children. The sensitivity and specificity of three methods of provocation, ie, histamine, nebulized water, and exercise, were compared in 20 asthmatic and 20 control children between ages 5 and 13 years. Three clinical categories of severity ranging from slight (Group 1) through moderate (Group 2) to severe asthma (Group 3) were identified. The three methods were compared in each subgroup for detecting a tendency to bronchospasm. An inverse correlation (-0.57) was found between the histamine dose and clinical degree of severity, whereas distilled water and exercise proved to be too insensitive for identifying Group 1 asthmatics. Histamine challenge in children is a safe and sensitive technique for identifying asthma and for monitoring the severity of the disease during follow up. PMID- 3344167 TI - On rigid or flexible bronchoscopies in children. PMID- 3344168 TI - Forced vital capacity and maximal respiratory pressures in patients with mild and moderate scoliosis. AB - Lung function and maximal respiratory pressures of 24 adolescent females with mild-to-moderate idiopathic scoliosis (spinal curvature 10-60 degrees) were determined and compared with 38 age- and sex-matched controls. Twelve patients with moderate scoliosis (Cobb angle 35-60 degrees) had significantly reduced mean values for FVC (% predicted) and maximal inspiratory pressure (MIP), as compared to the controls. Twelve patients with mild scoliosis (Cobb angle less than 35 degrees) had normal mean values for FVC and maximal respiratory pressures, but five individual patients had FVC values less than 80% predicted. All but one of the patients with mild scoliosis had normal MIP values. FVC (% predicted) was significantly correlated with the degree of spinal curvature (r = -0.466; P less than 0.05) but was not related to MIP. These results indicate that reduced FVC values do occur in patients with mild-to-moderate idiopathic scoliosis and suggest that these low FVC values can be attributed to the rib cage deformity rather than to an inability to generate adequate inspiratory pressures. PMID- 3344169 TI - Plasmid DNA analysis of Staphylococcus epidermidis isolated from blood and colonization cultures in very low birth weight neonates. AB - We prospectively studied the course of colonization and sepsis with Staphylococcus epidermidis among 29 very low birth weight neonates undergoing prolonged umbilical catheterization. S. epidermidis bacteremia occurred in 7 patients. In 6 bacteremia was preceded by positive colonization cultures. Isolates obtained from nares, base of umbilicus, umbilical catheter entry sites, catheter tips and blood were examined for plasmid DNA profiles. In 4 patients the plasmid profiles of the catheter entry site isolates were identical with those of the blood isolates. In the other 3 bacteremic patients plasmid profiles of the catheter entry site and blood isolates were different. No correlation was observed in the plasmid DNA patterns of isolates obtained from catheter tip cultures as compared to the corresponding blood cultures. The blood isolates from bacteremic patients had different plasmid profiles. PMID- 3344170 TI - Acanthameba meningoencephalitis masquerading as neurocysticercosis. PMID- 3344171 TI - Acute acalculous cholecystitis caused by Salmonella typhi in an 11-year-old. PMID- 3344172 TI - Prenatal screening for hepatitis B infection in the military population in Hawaii. PMID- 3344173 TI - Repeat lumbar puncture in the differential diagnosis of meningitis. PMID- 3344174 TI - Neonatal ocular prophylaxis. PMID- 3344175 TI - Giardiasis associated with the use of a water slide. AB - Although Giardia lamblia cysts are an important contaminant of surface water supplies, only one swimming pool outbreak, involving an infant and toddler swim class, has been reported. We describe an outbreak of giardiasis associated with a hotel's new water slide pool which was cleansed by both bromination and sand filtration. Among the 107 hotel guests and their visitors surveyed, 29 probable and 30 laboratory-confirmed cases of Giardia infection were found. Cases ranged from 3 to 58 years of age, with a mean age of 21 years. The 5-year modal age grouping was 5 to 10 years of age. Symptoms in the 59 cases included: diarrhea (48), cramps (38), foul smelling stools (29), loss of appetite (23), fatigue (20), vomiting (18), greasy stools (15), fever (11) and weight loss (10). Four children and 2 adults were hospitalized. Significant associations were found for staying at the hotel, using the water slide pool and swallowing pool water. A possible contributing factor was the emptying of an adjacent toddlers' wading pool, a potential source of fecal material, into the water slide pool. Transmission of Giardia can occur in water slide pools and therefore should be considered in cases of protracted diarrhea among users of such pools. PMID- 3344176 TI - First step in obtaining child health care: selecting a physician. AB - To investigate the process by which families identified and selected their children's current physicians, a close-ended questionnaire was administered to 750 families in a mail panel. Of 630 responses (84.0%), 244 had children in the home; 229 (93.9%) identified a regular and current physician for their youngest child. However, parents did not spend much time or energy selecting a physician and rarely explored medical expertise in their decisions. Families averaged 1.2 sources of information consulted per decision; few considered more than two physician choices and infrequently considered alternative types of doctors (pediatricians v family or general practitioners). Selection priorities ranked in order of importance concerned parents' perceptions of their doctors' communication skills, accessibility, and quality as determined by recommendations of friends or physicians. Parents appeared less concerned with issues of cost and convenience. Families selecting pediatricians differed from those selecting family and general practitioners in sources of information used and selection priorities. The survey also identified 84 families who had changed or seriously considered changing the physician who was caring for their youngest child. The most frequent dissatisfaction was the perception that an illness was not being managed adequately, followed by believing that the doctor or staff were rude or unconcerned. Families unhappy with pediatricians expressed different reasons from those unhappy with family or general practitioners. The study results provide insight about the first step in obtaining child health care services, a relatively unexplored area of patient decision making. PMID- 3344178 TI - Acquired immunodeficiency syndrome and secondary school students: their knowledge is limited and they want to learn more. AB - Information was gathered from 657 junior high school and senior high school students in two Connecticut school districts regarding their knowledge of acquired immunodeficiency syndrome (AIDS). Although many students had some factual knowledge about the virus that causes AIDS, many students were misinformed about methods of viral transmission, high-risk groups for acquiring AIDS, and methods to avoid acquisition of the virus. Most students did not recognize the existence of a carrier state. Responses from students of different grades, ages, sexes, races, and school districts differed rarely and without apparent pattern. Students reported that they had learned about AIDS mostly from television or radio (57%) or magazines or newspapers (16%); few had learned from persons with whom they had frequent contact, such as parents (6%) or teachers (4%). Seventy-four percent of students said they wanted to learn more about AIDS, and 49% said they wanted to learn it in school. Results of this study indicated that students' knowledge about AIDS is not adequate, students wish to learn more, and information about AIDS should be presented in public schools. PMID- 3344177 TI - Academic achievement in children ten to 12 years after Haemophilus influenzae meningitis. AB - Academic achievement by 23 children 10 to 12 years after treatment of Haemophilus influenzae meningitis was assessed using individually administered standardized tests, review of school transcripts, and parent and teacher questionnaires. The children's performance was compared with (1) their own performance in a previous study 6 to 8 years after the illness; (2) the performance of 23 similarly aged siblings in the previous study, a comparison which served to age match subjects and sibling controls; and (3) the performance of 11 of those similarly aged siblings retested in the current study. Subjects scored in the average range on all measures. Scores were comparable to results 4 years previous in four of six academic measures, with minor deterioration in reading single words and decoding nonsense words. There were no differences between subjects in the current study and control subjects from the previous study, except in decoding nonsense words, and no differences between subjects and control subjects in the current study, except in paragraph reading accuracy. Scholastic grade point averages and scores on parent and teacher behavior problem-rating scales showed no group differences. Subjects used more school-based remedial services, although the trend did not achieve statistical significance. Parents reported spending more time with subjects than with control subjects helping with homework. These findings suggest that children who have recovered from meningitis due to H influenzae can maintain scores and grades comparable to their siblings as they progress to middle school. Their academic success may involve more school and family support to compensate for the mild differences in intelligence quotient and neuropsychologic testing found in the previous study. PMID- 3344180 TI - Breast-feeding incidence and duration in black and white women. AB - The influence of sociodemographic factors on the incidence and duration of breast feeding was evaluated in 668 black and 511 white women delivering their first child in the metropolitan Washington, DC, area. Breast-feeding rates were 84% among white and 49% among black women. Maternal educational level was strongly associated with breast-feeding, whereas the effect of ethnicity was moderate. Women with some college or some graduate school education had adjusted odds of breast-feeding that were 2.6 (95% confidence limit 1.9 to 3.7) and 5.2 (95% confidence limit 2.7 to 10.2) times higher than women with a high school education or less. In contrast, the adjusted odds of breast-feeding were 2.0 (95% confidence limit 1.4 to 3.1) times higher for white women compared with black women. The odds of breast-feeding increased among black women if they attended childbirth classes, were married, or were older. Among black women, the frequency of breast-feeding decreased sharply by 1 month postpartum. Breast-feeding duration for black v white women was 74% v 90% at 1 month, 44% v 72% at 4 months, and 26% v 50% at 7 months postpartum. The majority of black women (53%) used formula supplements in the hospital, which was the only factor significantly related to a shortened duration in this group (P less than .01). The high rate of formula supplementation among black women and its strong association with shortened duration of breast-feeding point to a need for more advice and support and less reliance on formula during the hospital stay. PMID- 3344179 TI - Lack of adverse reactions to iron-fortified formula. AB - Some physicians are reluctant to recommend feeding of iron-fortified formulas to infants because of a fear of adverse reactions. In crossover studies, parents' records were compared with regard to their infant's behavior (fussiness, cramps, regurgitation, flatus, colic) and stool characteristics during periods when iron fortified formulas were fed and periods when non-iron-fortified formulas were fed. No statistically significant feeding-related difference was noted except for stool color. PMID- 3344182 TI - Respiratory origin of fluctuations in arterial blood pressure in premature infants with respiratory distress syndrome. AB - A variable fluctuating pattern of arterial BP often precedes intraventricular hemorrhage in mechanically ventilated preterm infants. To learn more about the origin of this pattern, arterial BP and respiratory muscle activity were studied in five intubated premature infants who were at high risk for intraventricular hemorrhage. We monitored esophageal pressure, gastric pressure, and arterial BP. Consistent findings were: (1) arterial BP fluctuations have the same frequency and direction of change as esophageal and gastric pressure changes associated with spontaneous breathing (R ranged from .93 to .98, P less than .001); (2) spontaneous apneic pauses were accompanied by sudden and complete cessation of arterial BP fluctuations; (3) large "cough-like" fluctuations in esophageal and gastric pressures, seen in all infants, were associated with the largest fluctuations in arterial BP; (4) cutaneous stimulation had negligible effect on fluctuation in arterial BP provided no change in esophageal and gastric pressures occurred; (5) the effects of change in esophageal and gastric pressures on arterial BP were nearly simultaneous (0.05 to 0.25 second latency); (6) respirator pressure fluctuations had negligible effects on the fluctuations in arterial BP. These data suggest that the fluctuations in arterial BP are directly related to respiratory muscle activity and are most consistent with the familiar pulsus paradoxus that occurs in various other cardiorespiratory diseases. PMID- 3344181 TI - Growth failure in infants with bronchopulmonary dysplasia: nutrition and elevated resting metabolic expenditure. AB - The mechanisms underlying growth failure in infants with bronchopulmonary dysplasia are poorly understood. Thirteen infants with bronchopulmonary dysplasia at 6 months of corrected age and 12 full-term healthy control infants matched for age or size were studied. Resting oxygen consumption was measured during natural sleep, and an estimation of the resting metabolic expenditure by indirect calorimetry was performed. Growth parameters were measured, and a nutritional profile including dietary intake, stool analysis, and serum albumin, cholesterol, glucose, and prealbumin was obtained. Seven of the 13 infants with bronchopulmonary dysplasia had growth failure (defined as length and weight less than the tenth percentile of the Babson growth curves). These infants had lower birth weight, lower gestational age, and a greater number of days spent in supplemental oxygen or on mechanical ventilation. There was no statistical difference between the bronchopulmonary dysplasia-growth failure and bronchopulmonary dysplasia-normal growth infants for dietary intake or stool or serum analyses. However, serum prealbumin showed a significant linear correlation with body weight in infants with bronchopulmonary dysplasia. Resting metabolic expenditure was elevated in infants with bronchopulmonary dysplasia with growth failure and was inversely correlated with body weight in all infants with bronchopulmonary dysplasia. Thus, infants with bronchopulmonary dysplasia and growth failure have increased metabolic demands and decreased prealbumin values suggesting a relative state of protein-calorie malnutrition. PMID- 3344183 TI - Mortality in very preterm and very low birth weight infants according to place of birth and level of care: results of a national collaborative survey of preterm and very low birth weight infants in The Netherlands. AB - As part of a collaborative project in the Netherlands in 1983, for which data were collected on 1,338 newborn infants (less than 32 weeks' gestation and/or less than 1,500 g birth weight), all infants were assigned to one of three levels of care according to hospital of birth. Considerable centralization was achieved by antenatal and neonatal transport. Although the uncorrected mortality rates were similar, the mortality odds (adjusted for four and 22 potential confounding perinatal factors, respectively) were significantly higher in level 1 and level 2 hospitals compared with level 3 hospitals (tertiary perinatal care centers). By extending the facilities for full perinatal intensive care in level 3 centers and thus providing optimal care for all such infants, the overall mortality rate is expected to decrease further. PMID- 3344184 TI - Behavioral responsiveness in preterm infants with intraventricular hemorrhage. AB - Preterm infants with varying degrees of intraventricular hemorrhage (none, n = 21; grade I to II, n = 22; grade II to IV, n = 24) and a group of full-term infants (n = 21) were compared with regard to behavioral responsiveness and parental reports of the infant's temperament. Behavioral responsiveness was assessed during the presentation of 15 visual, auditory, and tactile stimuli at 3 months of age (corrected age for preterm infants). Summary scores for positive and negative responsiveness, as well as sociability, soothability, and overall activity levels, were derived from behavioral observations by coders who were unaware of the infant's characteristics. The Bates Infant Characteristic Questionnaire was completed by the main care giver and scored on four summary variables: fussy-difficult, unadaptable, dull, and unpredictable. Preterm infants, regardless of the presence or severity of intraventricular hemorrhage, showed less positive responses and less overall activity in response to stimulation. Infants with grade I to II intraventricular hemorrhage were less sociable and more difficult to soothe than full-term control infants. Individual differences in positive, negative, sociability, and soothability were related to the questionnaire scores of fussy-difficult and unadaptability. Both prematurity and degree of intraventricular hemorrhage affect behavioral responsiveness and these individual differences are related to parental reports of the infant's temperament. PMID- 3344185 TI - Continuous skeletal muscle paralysis: effect on neonatal pulmonary mechanics. AB - Pancuronium bromide (Pavulon) is used to induce skeletal muscle paralysis in preterm infants, presumably for effective ventilatory support during acute respiratory failure. Twelve infants with respiratory failure were evaluated for sequential changes in pulmonary mechanics during continuous pancuronium administration (0.1 mg/kg every two to three hours) for more than 48 hours. The study weight of the neonates ranged from 980 to 2,950 g, and the postconceptional age ranged from 27 to 41 weeks. Pulmonary compliance, resistance, and resistive work of breathing were determined, using least mean square analysis technique, daily for three days and after discontinuation of pancuronium (even though there was no clinical improvement in ventilatory management). The dynamic pulmonary compliance decreased from 0.38 +/- 0.05 to 0.30 +/- 0.04 mL/cm H2O/kg (mean +/- SE) (P less than .05) and the total pulmonary resistance increased 51% from 115.6 +/- 21.3 to 174.9 +/- 27.3 cm H2O/L/s (P less than .005) during prolonged skeletal muscle paralysis. Upon discontinuation of pancuronium, the dynamic pulmonary compliance increased 43% to 0.43 +/- 0.4 mL/cm H2O/kg (P less than .05) and the total pulmonary resistance decreased by 41% (P less than .005). These data question the advisability of prolonged skeletal muscle paralysis in neonates and suggest the need for further detailed evaluation of the effects of prolonged paralysis on neonatal pulmonary mechanics. PMID- 3344186 TI - Vitamin K effect in low birth weight infants. AB - Factor II coagulant antigen (FII-AG), the protein induced by vitamin K absence or antagonist II (PIVKA-II), and coagulant activity (normotest) were measured in low birth weight infants. The factor II coagulant antigen and normotest levels in one day-old babies were lower than those of full-term infants (P less than .005, P less than .01, respectively). Infants whose normotest levels were less than 30% at one day (group A) received vitamin K2, and the others whose normotest levels were greater than 30% at one day (group B) were not treated. At this time, the mean factor II coagulant antigen level was significantly lower in group A than in group B (P less than .05). During the first seven days of life, in 65.2% of the infants in group B the PIVKA-II level became positive, but this did not occur in any infant in group A. After vitamin K treatment, there was greater improvement in the normotest level in infants with positive PIVKA-II levels than in those with negative PIVKA-II levels. This observation indicates that the hypoprothrombinemia found in low birth weight infants at one day of age is attributable to reduced synthesis of factor II coagulant antigen in the liver at this stage, but the prophylactic administration of vitamin K seemed to be effective even in such infants, probably because of the increase in factor II coagulant antigen synthesis (P less than .001) during the first seven days of life. PMID- 3344187 TI - Urine output determination from superabsorbent and regular diapers under radiant heat. AB - The rate of water evaporation from diapers was determined by sequential weights of open and closed regular diapers and of open superabsorbent diapers in three different environments--radiant heater at 100% heater output, radiant heater at 50% heater output, and room air. In all three environments, evaporation was greatest with open regular diapers, less with open superabsorbent diapers, and least with closed regular diapers. Evaporation was greatest under the radiant heater with 100% heater output, less under the radiant heater with 50% heater output, and least in room air. An open, regular diaper under 100% heater output lost 45% of its water after one hour and 85% had evaporated after two hours. Smaller volumes of water demonstrated a larger percentage of evaporation than larger volumes. Recommendations are made for the use of (1) either open, superabsorbent diapers or closed, regular diapers, (2) prompt weights after urination, and (3) accurate and precise scales. PMID- 3344188 TI - Thermal epiglottitis after swallowing hot beverages. AB - Two young children who sustained thermal injuries to the epiglottis (or "thermal epiglottitis") after swallowing hot beverages are reported. Findings, clinically and radiologically, in both children were similar to acute infectious epiglottitis. Children with these injuries are at risk for significant upper airway obstruction which may progress for several hours. Children in whom thermal epiglottitis is suspected should be approached with the same caution and preparedness for emergency airway management and pediatric intensive care afforded those with acute infectious epiglottitis. PMID- 3344189 TI - Coarctation of the aorta in Turner syndrome: a pathologic study of fetuses with nuchal cystic hygromas, hydrops fetalis, and female genitalia. AB - Congenital heart disease is a frequent feature of Turner syndrome. Although the most frequent cardiac lesion is coarctation of the aorta, a spectrum of cardiac defects occurs which is limited almost exclusively to defects associated with decreased blood flow through the left heart. We report the results of gross anatomic and microscopic dissection of 12 fetuses aborted between 16 and 26 weeks' gestation, with the classic Turner phenotype of nuchal cystic hygromas, hydrops fetalis, and female genitalia. Eight fetuses showed a consistent constellation of cardiac defects: diminution of the ascending aorta, large pulmonary artery ranging from 1 1/2 to three times the size of the aorta, large patent ductus arteriosus, and juxtaductal coarctation. Another fetus had hypoplastic left heart and aortic atresia. The remaining three fetuses had normal cardiac anatomy. The lymphatic vessels at the base of the great vessels were carefully examined in nine of the fetuses. Although there was no definite correlation between the degree of cardiac pathology and the extent of lymphatic aberrations at the base of the heart at the time of postmortem examination, the high incidence (75%) of left-sided flow defects among these fetuses, all of whom had large hygromas and severe edema, supports the hypothesis that there is a pathogenetic relationship between lymphatic obstruction and congenital heart disease in the 45,X Turner fetus. PMID- 3344190 TI - Overt glucocorticoid excess due to inhaled corticosteroid therapy. AB - Inhaled corticosteroids have become an important therapeutic option in the treatment of childhood asthma. The preparations currently available for pediatric use (beclomethasone dipropionate and triamcinolone acetonide) do not, in general, cause significant hypothalamic-pituitary-adrenal axis suppression and physical signs of glucocorticoid excess have not been described with their use. We report an 8-year-old girl with asthma in whom obesity, hirsutism, and growth retardation developed during treatment with inhaled triamcinolone acetonide alone. Laboratory studies showed suppression of endogenous cortisol production but did not demonstrate suppression of the hypothalamic-pituitary-adrenal axis. Cessation of inhaled triamcinolone acetonide therapy resulted in resolution of obesity and hirsutism, resumption of normal growth, and a return to normal of serum cortisol levels and urinary 17-hydroxycorticosteroid excretion. Careful monitoring of growth velocity and (if clinically indicated) morning serum cortisol levels in asthmatic children using inhaled corticosteroids will detect the rare instance of glucocorticoid excess resulting from systemic absorption of these drugs. PMID- 3344191 TI - Mother's milk and sewage: their interactive effects on infant mortality. AB - If they lived in households without piped water or a toilet, Malaysian infants who did not breast-feed were five times more likely to die after 1 week of age than those who breast-fed, when other significant factors affecting infant mortality were taken into account. This is double the relative risk associated with not breast-feeding for infants born into households with toilets, whether or not they had piped water. Analogously, improvements in toilet sanitation appear to have reduced mortality twice as much among infants who did not breast-feed as among those who did. These findings, from a retrospective survey of infants born to a probability sample of 1,262 women in peninsular Malaysia, confirm the pernicious synergistic effect of poor sanitation and nonbreastfeeding that was postulated previously on theoretical grounds. Promoting and maintaining high initiation of breast-feeding is thus particularly important where poor sanitation is prevalent. Even more affluent areas should not be neglected, however, because socioeconomic improvement, including improved environmental sanitation, is often accompanied by decreased breast-feeding. Although the risk to each nonbreast-fed infant was less in those areas, infants there were less likely to breast-feed in Malaysia, and hence they made up a significant proportion of lives that could be saved by breast-feeding. PMID- 3344192 TI - AIDS, children, and breast-feeding. PMID- 3344193 TI - Homosexual adolescents and confidentiality. PMID- 3344194 TI - Urine latex particle agglutination. PMID- 3344195 TI - Prognosis of renal failure. PMID- 3344196 TI - Disposable diaper damper. PMID- 3344197 TI - Telephone calls by working parents. PMID- 3344198 TI - Toy balloons and eye injuries. PMID- 3344199 TI - N4 virion DNA dependent-RNA polymerase: initiation sequences utilized by the enzyme on heterologous templates. AB - Bacteriophage N4 virion-encapsulated RNA polymerase, the enzyme responsible for transcription of the phage early RNAs, is unable to use duplex linear DNA as a template. In contrast to other RNA polymerases, the enzyme transcribes denatured N4 DNA with in vivo specificity. The promoter sequences for three sites of transcription initiation on the N4 genome have been determined and found to contain conserved sequences and two sets of inverted repeats. In order to define the minimal sequence requirements for N4 virion RNA polymerase activity, we have screened several heterologous DNAs, amounting to 64,328 bases, for their ability to support transcription. Several sequences allowing specific initiation were found. Their location, properties and the relation to N4 virion RNA polymerase promoters are discussed. PMID- 3344200 TI - Tissue-specific expression of the rat beta-casein gene in transgenic mice. AB - The rat beta-casein gene is a member of a small gene family, encoding the principal milk proteins. In order to understand the mechanisms by which its stage and tissue-specific expression are regulated, initially, a 14 kb genomic clone containing the entire 7.5 kb rat beta-casein gene with 3.5 kb of 5' and 3.0 kb of 3' flanking DNA was microinjected into the germline of mice. Eight F0 transgenic mice were generated with copy numbers ranging from 1-10; five transmitted the transgene to their offspring in a Mendelian pattern. A specific RNase protection assay was developed to quantitate the level of expression of the rat beta-casein transgene as compared to the endogenous mouse beta-casein gene. Using this assay expression was demonstrated predominantly in the lactating mammary gland of transgenic mice at a level of 0.01-1% of the endogenous mouse beta-casein gene. The transgene employed the authentic transcription initiation site observed previously in the analogous rat beta-casein gene. In one line, a reduced level of expression of the transgene was also observed in the brain. The site of integration, therefore, plays an important role in influencing the level of expression of the transgene, but not its general pattern of tissue-specificity. The transgene appears to be developmentally-regulated in accordance with the endogenous mouse beta-casein gene. These lines of mice generated carrying the rat beta-casein transgene should provide useful models for studying the developmental and hormonal regulation of milk protein gene expression. PMID- 3344201 TI - Helix stability and the mechanism of cruciform extrusion in supercoiled DNA molecules. AB - The kinetic properties of cruciform extrusion in supercoiled DNA molecules fall into two main classes. C-type cruciforms extrude in the absence of added salt, at relatively low temperatures, with large activation energies, while S-type cruciforms exhibit no extrusion in the absence of salt, and maximal rates at 50 mM NaCl, with activation energies about one quarter those of the C-type. These diverse properties are believed to reflect two distinct pathways for the extrusion process, and are determined by the nature of the sequences which form the context of the inverted repeat. C-type kinetics are conferred by A + T rich sequences, implying a role of helix stability in the selection. In this study we have shown that: 1. Helix-destabilising solvents (dimethyl formamide and formamide) facilitate extrusion by normally S-type molecules at low temperatures in the absence of salt. 2. C-type extrusion is strongly suppressed by low concentrations (2-4 microM) distamycin, at which concentrations S-type extrusion is enhanced. 3. Some extrusion occurs in a C-type construct in the presence of 50 mM NaCl. This is increased by addition of 3 microM distamycin, under which conditions extrusion becomes effectively S-type. Thus S-type constructs can behave in a quasi-C-type manner in the presence of helix-destabilising solvents, and C-type extrusion is suppressed by binding a compound which stabilises A + T rich regions of DNA. Helix destabilisation leads to C-type behaviour, while helix stabilisation results in S-type properties. These studies demonstrate the influence of contextual helix stability on the selection of kinetic mechanism of cruciform extrusion. PMID- 3344202 TI - Sequence of cDNAs for mammalian H2A.Z, an evolutionarily diverged but highly conserved basal histone H2A isoprotein species. AB - The nucleotide sequences of cDNAs for the evolutionarily diverged but highly conserved basal H2A isoprotein, H2A.Z, have been determined for the rat, cow, and human. As a basal histone, H2A.Z is synthesized throughout the cell cycle at a constant rate, unlinked to DNA replication, and at a much lower rate in quiescent cells. Each of the cDNA isolates encodes the entire H2A.Z polypeptide. The human isolate is about 1.0 kilobases long. It contains a coding region of 387 nucleotides flanked by 106 nucleotides of 5'UTR and 376 nucleotides of 3'UTR, which contains a polyadenylation signal followed by a poly A tail. The bovine and rat cDNAs have 97 and 94% nucleotide positional identity to the human cDNA in the coding region and 98% in the proximal 376 nucleotides of the 3'UTR which includes the polyadenylation signal. A potential stem-forming sequence imbedded in a direct repeat is found centered at 261 nucleotides into the 3'UTR. Each of the cDNA clones could be transcribed and translated in vitro to yield H2A.Z protein. The mammalian H2A.Z cDNA coding sequences are approximately 80% similar to those in chicken and 75% to those in sea urchin. PMID- 3344203 TI - Preliminary spectroscopic characterization of a synthetic DNA oligomer containing a B-Z junction at high salt. AB - It is well known that the local conformation of a segment of DNA is dependent upon both the sequence of the segment and the conditions under which the DNA is prepared. In extreme cases, the DNA may contain regions of both right and left handed conformations, mandating the existence of a conformational junction between the two. These B-Z junctions have been observed in plasmids but, to date, no model systems have been characterized to determine the molecular nature of these junctions. Preliminary CD, UV, and NMR studies on such a model are presented here. A 16 base pair oligonucleotide, containing a potential B-Z junction, has been synthesized and characterized by the above techniques. The results suggest that this molecule contains both right and left-handed conformations under condition of high salt, and thus a B-Z junction. PMID- 3344205 TI - Nucleotide sequence of a mouse minisatellite DNA. PMID- 3344204 TI - Sensitive non-radioactive dot-blot hybridization using DNA probes labelled with chelate group substituted psoralen and quantitative detection by europium ion fluorescence. AB - A new labelling method for cloned DNA probes used in hybridization assays is described. The DNA insert of recombinant plasmid DNA was made partially single stranded for the labelling reaction by a restriction enzyme digest, followed by a controlled exonuclease III incubation. A thiol-containing psoralen derivative was covalently bound through irradiation with UV-light to the remaining double stranded region of the plasmid DNA. The psoralen-SH groups were labelled with a large number of metal chelators (diethylentriamine pentaacetic acid, DTPA) using poly-L-lysine as a macromolecular carrier. The main advantage of the labelling procedure is that a high degree of labelling is achieved without modification of the single-stranded DNA hybridizing sequences. The specific hybrids were labelled after filter hybridization with europium ions through the chelating groups of DTPA. The europium ions were quantitatively detected by time-resolved fluorometry. The sensitivity of the assay for target DNA detection was in the low picogram range, comparable to radioactively labelled DNA probes. PMID- 3344206 TI - The soybean chloroplast genome: complete sequence of the rps19 gene, including flanking parts containing exon 2 of rpl2 (upstream), but rpl22 (downstream). PMID- 3344207 TI - The soybean chloroplast genome: nucleotide sequence of a region containing tRNA Val (GAC) and 16S rRNA gene. PMID- 3344208 TI - Sequence heterogeneity in mouse centromeric sDNA. PMID- 3344209 TI - Complete coding sequences of the ras related rab 3 and 4 cDNAs. PMID- 3344211 TI - A simple and efficient method for isolating high molecular weight DNA from mammalian sperm. PMID- 3344210 TI - Sequence of a 1.4 kb Eco RI fragment of Azotobacter vinelandii nif DNA. PMID- 3344212 TI - Nucleotide sequence of a wheat mitochondrial glutamine tRNA gene. PMID- 3344213 TI - Novel type of splice junctions in the chicken cartilage matrix protein gene. PMID- 3344214 TI - A sensitive, bioluminescent-enhanced detection method for DNA dot-hybridization. PMID- 3344215 TI - The nucleotide sequence of chicken smooth muscle myosin light chain two. PMID- 3344216 TI - A simple salting out procedure for extracting DNA from human nucleated cells. PMID- 3344217 TI - The nucleotide sequence of the tetracycline resistance determinant tetM from Ureaplasma urealyticum. PMID- 3344219 TI - Double stranded DNA sequencing as a choice for DNA sequencing. PMID- 3344218 TI - Nucleotide sequence of a ligninase gene from Phanerochaete chrysosporium. PMID- 3344220 TI - alpha-DNA. VII. Solid phase synthesis of alpha-anomeric oligodeoxyribonucleotides. AB - An efficient procedure for the synthesis of unnatural alpha-anomeric oligodeoxyribonucleotides is described. This solid-phase procedure is based on the use of alpha-nucleoside phosphoramidites and alpha-nucleoside derivatized solid supports corresponding to the four natural bases and allow rapid synthesis of oligonucleotides up to 20 alpha-deoxynucleotide units in length. After HPLC purification, a 15-mer: alpha-d(CCTCTCGTTCTTTAC) and a 20-mer: alpha d(ATACTTGAGGAAGAGGTGTT) were obtained respectively in 27 and 29% overall yields. Their purity, nucleoside composition and primary structure were ascertained by HPLC and Maxam-Gilbert sequence analyses. PMID- 3344221 TI - Grapevine yellow speckle viroid: structural features of a new viroid group. AB - A single stranded circular RNA was isolated from grapevines infected with yellow speckle disease. The RNA which we have called grapevine yellow speckle viroid (GYSV), contains 367 nucleotide residues and has the potential to form the rod like secondary structure characteristic of viroids. GYSV has 37% sequence homology with the recently described apple scar skin viroid (ASSV; 330 residues) and has some sequence homology with the viroids in the potato spindle tuber viroid (PSTV) group. The sequence of GYSV has characteristics which fit the structural domains described for the PSTV group. However, GYSV lacks the PSTV central conserved sequence. Instead, there is a conserved sequence in the central region of GYSV and ASSV which has the potential to form a stem loop configuration and a stable palindromic structure as does the central conserved region of the PSTV group. These structural features suggest there is a different central conserved region for GYSV and ASSV. The results support the viroid nature of GYSV and its inclusion into a separate viroid group which we suggest should be represented by ASSV. PMID- 3344222 TI - Joining of nonhomologous DNA double strand breaks in vitro. AB - Extracts of Xenopus laevis eggs can efficiently join ends of duplex DNA that differ in structure and sequence. This was analysed by recircularisation of linear plasmid DNA molecules with dissimilar termini, generated by successive cuts with two different restriction enzymes within the pSP65 polylinker. Use of various enzymes provided blunt ended or 4 nucleotides long 3' and 5' protruding single strand (PSS) termini which were successfully joined in vitro in any tested combination. Sequence analysis of numerous junctions from cloned reaction products of 7 terminus combinations reveal: apart from very rare base exchanges and single nucleotide insertions less than 10% deletions (1 to 18 nucleotides long) were detected. Blunt/PSS or 3'PSS/5'PSS terminus pairs undergo simple "blunt end" joining which preserves PSS ends by fill-in. In contrast, equally polar 3'PSS/3'PSS or 5'PSS/5'PSS terminus pairs are joined by a complex mode: PSS ends overlap by a defined number of nucleotides, set by matching basepairs. Even one basematch suffices to define the setting. This then determines the final mismatch repair and fill-in pattern. We propose that yet unknown terminal DNA binding proteins stabilize the energetically highly unfavorable configuration of single matching basepairs and help to support defined overlap structures. PMID- 3344223 TI - Characterization of the 'unusual' mobility of large circular DNAs in pulsed field gradient electrophoresis. AB - Large circular amplified DNAs (30 and 85 kb) present in methotrexate-resistant Leishmania major appear to migrate anomalously in pulsed field-gradient electrophoresis (PFGE), exhibiting pulse time-dependent mobility and migrating along a different apparent path relative to the large linear chromosomal DNAs. Quantitative studies indicate that the relative pulse-time dependence is actually conferred by the mobility properties of the large linear DNAs. One contributing factor to the difference in migration path is variability in the intrinsic voltage-dependence of mobility of supercoiled and linear DNAs, in combination with the asymmetrical/inhomogeneous voltage gradients. Certain linear chromosomes exhibit a previously undescribed pulse-time dependence in the voltage-dependence of mobility. When enzymatically relaxed or physically nicked the large circular DNAs fail to leave the well using any pulse time, a property also observed in conventional electrophoresis. These findings are relevant to PFGE theory, and its application to the study of circular DNA amplification in Leishmania and other species. PMID- 3344224 TI - YTS: an answer or irrelevance? PMID- 3344225 TI - The right to say no. PMID- 3344227 TI - Another kind of loss. PMID- 3344226 TI - Tired of it all. PMID- 3344228 TI - Screening needs staffing. PMID- 3344229 TI - Crisis? What crisis? PMID- 3344230 TI - Caring for Julie. PMID- 3344231 TI - Drug-giving for enrolled nurses. PMID- 3344232 TI - Autologous blood transfusion. PMID- 3344233 TI - Ethnic minorities. Culture shock. PMID- 3344234 TI - Working with Pat-Man. PMID- 3344235 TI - Combating the pressure. PMID- 3344236 TI - Young offenders. PMID- 3344237 TI - A mother of invention. PMID- 3344239 TI - Widening horizons. Interview by Laurence Dopson. PMID- 3344238 TI - Patients' sleep-wake rhythms in hospital. Part 2. PMID- 3344240 TI - Tissue viability. Wound care. PMID- 3344241 TI - Tissue viability. The good wound guide. PMID- 3344242 TI - Tissue viability. An age-old problem. PMID- 3344243 TI - Nursing rounds: idea to reality. PMID- 3344244 TI - Group intervention for reinforcing self-worth following mastectomy. PMID- 3344246 TI - The practice of TSE among college men: effectiveness of an educational program. PMID- 3344245 TI - Phantom breast experiences after mastectomy. PMID- 3344247 TI - Oncology nurses' attitude and behaviors related to sexuality of patients with cancer. PMID- 3344248 TI - IVADs for AIDS-KS patients: an acceptable standard? PMID- 3344249 TI - What happens now? A book to be read to children who have lost a loved one. PMID- 3344252 TI - Having fun with art. PMID- 3344251 TI - Reflections of a caregiver in pediatric oncology on coping. PMID- 3344250 TI - We have special needs too. PMID- 3344253 TI - Thyroid disease in the elderly. Special features, changes in management. AB - Many changes in thyroid physiology occur with aging. These changes correlate with major alterations in the normal physiologic functioning of the thyroid and with changes in thyroid hormone levels as measured by radioimmunoassay. Clinical manifestations of thyroid disease in elderly patients may be somewhat different than in younger patients. Both hyperthyroidism and hypothyroidism can be more difficult to diagnose in elderly patients because of subtle changes in disease presentation. The incidence of certain thyroid diseases, from benign single nodules to malignant anaplastic carcinoma, increases with age. A deliberate and cautious approach is needed when treating thyroid disease in the elderly, who are inherently more fragile than younger patients. PMID- 3344254 TI - Premenstrual syndrome. Seven steps in management. AB - Many forms of therapy for premenstrual syndrome (PMS) are available, but appropriate therapy involves more than a pill, more than changing attitudes, and more than removing stress. Even with treatment, the problems that preceded the PMS may persist and those that have been created by it may be slow to resolve. However, most patients experience significant improvement in their sense of well being and quality of life with appropriate, multidisciplinary therapy. PMID- 3344255 TI - Compulsive gambling: treatment is the real issue. PMID- 3344256 TI - Exercise during pregnancy. PMID- 3344257 TI - Silent myocardial ischemia. Answers to frequently asked questions. AB - Patients with coronary artery disease and silent myocardial ischemia have a prognosis similar to that of symptomatic patients. Screening of totally asymptomatic patients is not likely to identify many with silent ischemia. However, certain cohorts of patients--middle-aged men with two or more risk factors for coronary arteriosclerosis--are at risk of presenting initially with myocardial infarction or sudden death, and the screening of such persons is advised. Use of radionuclear imaging techniques during exercise stress testing appears to be helpful in identifying patients at high risk, who should then be offered coronary arteriography. An ideal treatment has not been established, but a treatment strategy based on symptom relief alone is suboptimal. Measures used for symptomatic ischemia are just as effective with silent ischemia. Treatment must be individualized, and ambulatory electrocardiographic monitoring appears useful in adjusting antiischemic therapy for a given patient. PMID- 3344258 TI - Skull fractures. Dispelling some misconceptions affecting management. PMID- 3344259 TI - Do you think...the insulin pump is a good treatment method for diabetic patients? PMID- 3344260 TI - Coughing up a stone. What to do about broncholithiasis. AB - Broncholithiasis, a disease that is probably much more common than has been reported, is most often associated with pulmonary infections, for example, tuberculosis and histoplasmosis. Stones originate from calcified peribronchial lymph nodes that erode into the tracheobronchial tree, but lithoptysis occurs infrequently. The most common symptoms are persistent cough and hemoptysis, sometimes followed by findings of obstructive pneumonia (fever, chills, and purulent sputum). Physical findings are nonspecific, and radiologic findings are varied. Complications include formation of a fistula between the respiratory tract and the esophagus or aorta and obstructive pulmonary symptoms. Treatment ranges from conservative management (simple observation) to thoracotomy for patients in whom complications from stone erosion develop. The prognosis of patients with broncholithiasis is generally excellent. PMID- 3344262 TI - Prenatal diagnosis of del(11)(p13p15). AB - Prenatal diagnosis of del(11)(p13p15) was made on cultured amniotic fluid cells and confirmed on fetal skin fibroblasts after termination of pregnancy. Both irides appeared behind schedule in development by 2-3 weeks in reference to the gestational age of the fetus. It is suggested that the aniridia of the aniridia- Wilms tumour association is due to developmental arrest. Confirmation of this complex is difficult at mid-gestation without critical pathological study of the eyes. PMID- 3344261 TI - Gastritis. Bringing this enigma into sharper focus. AB - Type A and type B (probably Campylobacter pylori) gastritis are distinct clinical (but largely asymptomatic) and histologic entities that can be separated from other disease processes. While the association of C pylori gastritis with peptic ulcer disease is well documented, no causal relationship has been established. Acute inflammatory conditions of the stomach secondary to other disease processes, macroscopic abnormalities of the gastric mucosa, and sometimes poorly characterized epigastric pain all carry the name "gastritis." The fact that, as a disease, gastritis remains an enigma largely stems from the multiple implications of the term. An accurate classification system of the gastritides would be helpful but is not yet available. Until it is, the term "gastritis" will have more meaning if accompanied by a description of the type of gastritis or of the responsible etiologic factor, secondary disease, or toxic insult (eg, gastric mucosal injury associated with use of nonsteroidal antiinflammatory drugs). Deletion of the term "gastritis" from the clinical vocabulary and substitution of better terms (eg, "nonulcer dyspepsia," "irritable bowel syndrome") will also serve to clarify the issue. PMID- 3344263 TI - Prenatal cytogenetic diagnosis after transabdominal chorionic villus sampling in the first trimester. AB - First trimester prenatal cytogenetic diagnosis was attempted in 350 pregnancies after transabdominal chorionic villus sampling. The cytogenetic investigation was performed using both a short-term method (24 h incubation) and cell culture. Adequate samples were obtained in 99.1 per cent and in all these cases the fetal karyotype was established. A chromosome abnormality was found in 2.0 per cent of cases. A discrepancy between the karyotype obtained after 24 h incubation and the karyotype in cell culture was observed in 2.3 per cent. Maternal cell contamination in the cultures was confirmed in 13 of 181 cases where the 24 h incubation revealed a male karyotype. Studies of culture morphology showed that colonies of convoluted cells may serve as a marker for contamination with maternal cells in culture. For the present, we recommend using a short-term method as well as cell culture for cytogenetic investigation until the problems with karyotype discrepancy and maternal cell contamination have been further clarified. PMID- 3344265 TI - Electromagnetic fields and neurobehavioral function. PMID- 3344264 TI - Fetal bradyarrhythmia: diagnosis and outcome. AB - Seventeen patients were referred to out ultrasound unit because of fetal bradyarrhythmia (less than 100 bpm). Duration of pregnancy varied between 21 and 40 weeks. Bradyarrhythmia was diagnosed as atrioventricular block (n = 12), mild sinus bradycardia (n = 3), and irregular bradycardia (n = 2). The association with maternal collagen disease was 29 per cent and with cardiac structural defects 59 per cent. The overall mortality was 41 per cent. There were three abnormal karyotypes (17 per cent) and four cases of cardiac compromise (23 per cent). Prognosis depends on the nature of the bradyarrhythmia and recognition of associated pathology such as cardiac structural defects, abnormal karyotype and degree of cardiac compromise. PMID- 3344266 TI - Stimulation of brain tissue in vitro by extremely low frequency, low intensity, sinusoidal electromagnetic fields. PMID- 3344267 TI - Effects on the nervous system by exposure to electromagnetic fields: experimental and clinical studies. AB - Exposure to electromagnetic fields may cause various types of effects on nervous tissue, in severe cases even irreversible damage. The exposure conditions, i.e. frequency including type and extent of modulation, time, intensity, wave form, as well as shape, size and position of exposed subject and possible treatment with drugs, are factors determining if damage, acute or chronic, ultimately result. Long term exposure of newborn rabbits, rats and mice to electromagnetic fields of power frequency (10-14 kV/m; 50 or 60 Hz; sinusoidal wave form; 21-24 h per day) may cause affection and even damage to the nervous system. Large nerve cells showed reactive changes such as lamellar bodies and cytoskeletal alteration to an extent varying with exposure conditions. Reactive neuroglial changes as well as increase in neuroglial marker proteins could concomitantly be demonstrated. The changes seemed to be reversible although we only have incomplete data available. Exposure in vitro of frog sciatic nerve to 16-60 Hz sinusoidal low current (50 1000 nA) for 17 h induced cytoskeletal changes. Exposure of rabbits to pulsed microwaves of moderate to high intensity (3.1 GHz; 300 Hz modulation; peak duration 1.4 usec with maximal peak intensity about 1000 times average; 55 mW/cm; SAR in the brain cortex about 20 W/kg; increase of temperature as measured by lightguide-equipped instruments in right brain hemisphere about 1-2 degrees C) during 1 h per day during three days resulted in no obvious initial changes in behaviour. Minimal acute dam- age could be demonstrated. However, after two to four months and later on both structural, immunohistochemical and biochemical changes could be documented. Radar technicians accidently and/or occupationally exposed to microwaves showed psychoneurological signs of affection as well as changes in cerebrospinal fluid protein pattern. No related changes have been noticed among matched controls. Exposure of nervous tissue to electromagnetic fields ranging from power frequency to microwaves may thus exert a wide range of effects, mostly by mechanisms we know little about. PMID- 3344268 TI - Morphological changes in cerebellum of neonatal rats exposed to 2.45 GHz microwaves. AB - One-day and six-day old Sprague-Dawley rats were exposed in the far field to 2.45 GHz (cw) microwaves at 10 mW/cm2 for five consecutive days, 7 hours per day (SAR 2W/kg). Pups were euthenized one day after exposure and the cerebella processed for light and electron microscopy. Matching cerebellar sections and folia from irradiated and sham irradiated animals were examined. Light microscopic examination revealed the presence of small deeply-stained cells with hyperchromatic pyknotic nuclei within the external granular layer (EGL). The number of these pyknotic cells in the experimental animals was nearly twice that in the controls. The Nissl bodies in Purkinje cells were finely dispersed. In some experimental animals mononuclear cellular infiltration was demonstrated. Under the electron microscope the deeply-stained pyknotic small cells presented electron dense nuclei with clumped chromatin, extrusion or disintegration of the nucleus, ruptured nuclear membrane, and the vacuolization of the cytoplasm. Eventually these cells became phagocytosed by surrounding EGL cells. Most of the Purkinje cells of experimental animals showed small, disorderly arrays of rough endoplasmic reticulum (RER) instead of the typical orderly stacks of parallel arrays. These observations suggest that microwave radiation may interfere with early genesis of cerebellar microneurons and alter the metabolic status of Purkinje cells. However, this effect might be reversible. PMID- 3344269 TI - Microwave effects on the cardiovascular system: a model for studying the responsivity of the autonomic nervous system to microwaves. PMID- 3344270 TI - Thermoregulatory responses in the rhesus monkey during exposure at a frequency (225 MHz) near whole-body resonance. PMID- 3344271 TI - Microwaves as reinforcing events in a cold environment. PMID- 3344272 TI - Prenatal microwave exposure and behavior. AB - The hypotheses for the initial investigation was based on the idea that failure to observe structural teratogenesis following microwave exposure did not preclude the possibility that such exposure would result in behavioral changes. We also proposed that such exposure might specifically alter some aspect of thermoregulatory behavior. The results of these studies support both of these hypotheses. Whether the studies show enhanced thermal sensitivity or enhanced development, they do support the hypothesis that prenatal exposure to microwave radiation is more likely to alter postnatal sensitivity to thermally related stimuli or conditions as compared to stimuli that are thermally neutral. PMID- 3344274 TI - Microwave--drug interactions in the cholinergic nervous system of the mouse. PMID- 3344273 TI - Reduced exposure to microwave radiation by rats: frequency specific effects. AB - Previous research has shown that SAR "hotspots" are induced within the laboratory rat and that the resulting thermal hotspots are not entirely dissipated by bloodflow. Two experiments were conducted to determine if hotspot formation in the body and tail of the rat, which is radiation frequency specific, would have behavioral consequences. In the first experiment rats were placed in a plexiglas cage one side of which, when occupied by the rat, commenced microwave radiation exposure; occupancy of the other side terminated exposure. Groups of rats were tested during a baseline period to determine the naturally preferred side of the cage. Subsequent exposure to 360-MHz, 700-MHz or 2450-MHz microwave radiation was made contingent on preferred-side occupancy. A significant reduction in occupancy of the preferred side of the cage, and hence, microwaves subsequently occurred. Reduced exposure to 360-MHz and 2450-MHz microwaves at 1, 2, 6 and 10 W/kg were significantly different from 700-MHz microwaves. In the second experiment semichronic exposures revealed the threshold for reduced exposure of 2450-MHz microwaves to be located between whole-body SAR's of 2.1 and 2.8 W/kg. PMID- 3344275 TI - People in 50 Hz electric and magnetic fields: studies in the United Kingdom. PMID- 3344276 TI - Possible physiological mechanisms for neurobehavioral effects of electromagnetic exposure. PMID- 3344277 TI - Electromagnetic waves and neurobehavioral function. Comments from clinical medicine. PMID- 3344278 TI - The magnetic detection system of the pigeon: involvement of pineal and retinal photoreceptors and the vestibular system. PMID- 3344279 TI - Human magnetoreception for navigation. PMID- 3344280 TI - Photoreactions of tris(2,2'-bipyridyl)-ruthenium(II) with peroxydisulfate in deoxygenated aqueous solution in the presence of nucleic acid components, polynucleotides, and DNA. PMID- 3344281 TI - Excision repair of UVR-induced pyrimidine dimers in corneal DNA. PMID- 3344282 TI - Picosecond resolution of indole anisotropy decays and spectral relaxation by 2 GHz frequency-domain fluorometry. PMID- 3344283 TI - The action spectrum in drug induced photosensitivity. PMID- 3344284 TI - Photochemical properties of porphyrin c: an agent for use in tumor phototherapy. PMID- 3344285 TI - Photochemical transformations in salicylanilide photoallergy. PMID- 3344287 TI - Acrylamide and molecular oxygen fluorescence quenching as a probe of solvent accessibility of aromatic fluorophores complexed with DNA in relation to their conformations: coronene-DNA and other complexes. PMID- 3344288 TI - Spectroscopic investigation of dihydronicotinamides--II. Dihydronicotinamide adenine dinucleotide complexes with dehydrogenases. PMID- 3344289 TI - Phosphorescence from 2-(p-toluidinyl)naphthalene-6-sulfonate and 1 anilinonaphthalene-8-sulfonate, commonly used fluorescence probes of biological structures. PMID- 3344290 TI - Biological activities of phthalocyanines--VIII. Cellular distribution in V-79 Chinese hamster cells and phototoxicity of selectively sulfonated aluminum phthalocyanines. PMID- 3344286 TI - A comparative study of the photochemistry of the non-steroidal anti-inflammatory drugs, naproxen, benoxaprofen and indomethacin. PMID- 3344291 TI - Photosensitization of neoplastic cells by anthrapyrazoles. PMID- 3344292 TI - The dose-response relationship of tumorigenesis by ultraviolet radiation of 254 nm. PMID- 3344293 TI - Effect of chronic UV exposure on epidermal forward scattering-absorption in SK-1 hairless mouse skin. PMID- 3344295 TI - 16th annual meeting of the American Society for Photobiology. Abstracts of papers. Colorado Springs, Colorado, 13-17 March 1988. PMID- 3344296 TI - Communication gap. PMID- 3344297 TI - Physiology research in Zimbabwe. PMID- 3344294 TI - The development of exciton migration routes for phycocyanin 645 and allophycocyanin. PMID- 3344298 TI - Caffeine, mental stress, and risk for hypertension: a cross-cultural replication. AB - Separate and combined effects of caffeine and mental arithmetic stress on systolic blood pressure (SBP) and heart rate (HR) were assessed in a double blind, placebo-controlled study. Thirty-six Chinese nationals, half with and half without a family history of hypertension, received either 0, 125, or 250 mg of caffeine in three separate experimental sessions, each preceded by a 12-hour abstention from caffeine consumption. Caffeine and mental stress elevated SBP, but caffeine did not potentiate the SBP response to mental stress. Caffeine did not affect HR. A positive family history of hypertension was associated with larger SBP elevations to the higher dose of caffeine. Family history of hypertension was associated with larger blood pressure elevations during mental stress, but only under conditions of high-level stimulation provided by the initial exposure to the stress. These results support previous findings of greater cardiovascular reactivity to laboratory stress in individuals at high risk for hypertension. PMID- 3344299 TI - Effects of menstrual phase and parental history of hypertension on cardiovascular response to cognitive challenge. AB - The effects of parental history of hypertension and menstrual phase on systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) responses to two frustrating cognitive tasks were examined in 47 normotensive, young adult women. Subjects with and without a parental history of hypertension were scheduled to be tested during either the follicular (days 7-11 of a 28-day cycle) or luteal (days 17-22) phase of the menstrual cycle. During the laboratory session, HR, SBP, DBP, and self-report of affective states were measured while subjects performed two cognitive tasks (mental arithmetic and concept formation). Results indicated that the magnitude of SBP responses to the two tasks was significantly greater in subjects tested during the follicular phase than in subjects tested in the luteal phase of the menstrual cycle. No effect of parental hypertension was observed on cardiovascular response measures, though offspring of hypertensive parents reported experiencing significantly less anger during the tasks than subjects with normotensive parents. PMID- 3344300 TI - Presidential address. Medicine and the Psychosomatic Society. PMID- 3344301 TI - Improving blood pressure estimation through internal and environmental feedback. AB - Different bodily sensations and situational factors covary with changes in systolic blood pressure (SBP). The present experiment explored whether an awareness of SBP-related cues could help individuals to estimate their own SBP levels more accurately. Sixty-four adults (53 women and 11 men) participated in two experimental sessions 3 months apart. Immediately following each of 13 task and intervening baseline periods of each of the two sessions, subjects estimated their SBP and rated the degree to which they were experiencing each of 10 physical symptoms and moods (i.e., internal cues). In addition, independent judges rated the extent to which various situational factors were present during each task and baseline. Within-subject correlations between internal and situational cues with SBP served as the basis for subjects' receiving one of four randomly assigned types of feedback: no feedback, internal cue feedback, situational cue feedback, or biosituational feedback based on both internal and situational cues. In the second experimental session 3 months later, subjects in the biosituational feedback condition were significantly better at estimating SBP than were individuals in any of the other conditions. Implications of biosituational feedback as an alternative to traditional biofeedback are discussed. PMID- 3344302 TI - Influences of sex and age on cardiovascular responses during stress. AB - The present investigation examined the influence of sex and age on blood pressure and heart rate responses in 125 women, 93 men, 121 girls, and 96 boys to three standardized stressors: serial subtraction, mirror-image tracing, and isometric handgrip. With baseline measures and body mass index controlled for, analyses of covariance showed that adults had greater systolic blood pressure responses than did children; men had greater blood pressure responses to all stressors than did women; and high school boys had greater systolic blood pressure responses than did high school girls. In addition, adults had smaller heart rate responses during isometric handgrip than did children, and high school students had smaller heart rate responses during all tasks than did the remaining, younger students. These results show that sex and age are important determinants of the magnitude of cardiovascular adjustments during stressors. The implications of these results are discussed in light of sex differences in coronary heart disease morbidity and mortality. PMID- 3344303 TI - Racial differences in blood pressure and forearm vascular responses to the cold face stimulus. AB - The mechanisms responsible for the higher incidence of essential hypertension in blacks than in whites are the object of much research attention. One hypothesis is that the development of hypertension in blacks is associated with exaggerated blood pressure reactivity, particularly those responses mediated by vasoconstriction. Racial differences in blood pressure responses to cold stimulation of the forehead, a known alpha-adrenergic vasoconstrictive stimulus, were examined in health, college-age males. Compared to white subjects, black subjects exhibited significantly greater increases in systolic and diastolic blood pressure, as well as increases in forearm vascular resistance, in response to cold stimulation. This preliminary evidence of increased peripheral vascular reactivity in blacks suggests that known racial differences in hypertension prevalence might derive in part from physiological differences in sympathetic nervous system reactivity. PMID- 3344304 TI - The stress interview as a tool for examining physiological reactivity. AB - Most studies of cardiovascular reactivity utilize tasks that are highly standardized and controlled. However, there is some concern whether the information obtained from these tasks is relevant to understanding the cardiovascular responses to behavioral stimuli encountered in real life. Historically, various forms of a stress interview have been used to examine physiological concomitants of emotional arousal. However, these tools fell into disuse because of ethical concerns, their intensive time requirements, and the perception that the interviews could not be standardized. We have developed a short (16-minute) interview that is not aversive or threatening. In studies on 24 normotensives and 19 hypertensives, the interview elicited greater blood pressure elevations than those elicited by mathematical calculations or cold pressor (p less than 0.0001). The interview increased systolic and diastolic pressures by 38/32 mm Hg in hypertensives and 31/24 mm Hg in normotensives. The variance in BP elicited by this interview is not appreciably greater than that found in highly structured tasks such as mathematical calculations. The test-retest stability of the interview is comparable to that of resting baseline blood pressure and is superior to that of mathematical calculations or cold pressor. Techniques such as the interview may be at least as useful as highly standardized tasks and possibly more valid as models for examining cardiovascular reactivity. PMID- 3344305 TI - Treatment of depression in cancer patients is associated with better life adaptation: a pilot study. AB - Major depression occurs in a significant number of cancer patients, and there is evidence that cancer patients with depression do not receive adequate antidepressant treatment. In an uncontrolled pilot study, the authors assess the degree of depression and the quality of life after the initiation of antidepressant medication treatment in 12 depressed cancer patients who received adequate antidepressant drugs and in 10 depressed cancer patients who received inadequate antidepressant treatment. These preliminary findings suggest that cancer patients with major depression benefit from antidepressant medication treatment and may experience an improved psychosocial adjustment to cancer. Controlled clinical trials will be necessary to verify these preliminary findings. PMID- 3344307 TI - Power frequency magnetic field and illness in multi-storey blocks. PMID- 3344306 TI - Cluster analysis of insomniacs' MMPI profiles: relation of subtypes to sleep history and treatment outcome. AB - The Minnesota Multiphasic Personality Inventory (MMPI) profiles of 100 insomniacs who presented for treatment at a university medical center were analyzed by a hierarchical clustering procedure. This analysis revealed two major personality types that accounted for 88% of the sample. The two types referred to as "Type 1" and "Type 2" insomniacs differed significantly in regard to sleep history questionnaire responses and responsivity to treatment. MMPI scales and sleep history questionnaire items suggested that Type 1 insomniacs were less defended, more aroused/activated, and had sleep histories characterized by more childhood sleep problems and greater difficulties with sleep-disruptive cognitions than did Type 2 patients. Further, Type 1 patients had a poorer response to behavioral treatment as measured by change in sleep-onset latency than did Type 2 patients. These results suggest that the MMPI may be useful in identifying distinctive personality subgroups among insomniacs. Treatment implications are discussed, and mechanisms underlying the group differences are considered. PMID- 3344308 TI - Health care in Cuba. PMID- 3344309 TI - Sporting motorcycle accidents in children. PMID- 3344310 TI - Attenders and non-attenders at a breast screening clinic: a comparative study. PMID- 3344311 TI - Regional socioeconomic differences in mortality among men in Great Britain today. PMID- 3344312 TI - The risk of stroke in young adults: an analysis of the contribution of cigarette smoking and alcohol consumption. PMID- 3344313 TI - Racial differences in rubella immunity among pregnant women. PMID- 3344314 TI - The apparent effect of Asian immigrants on the Heaf reactivity in Derby schoolchildren. PMID- 3344315 TI - Eye problems among cement factory workers in Bendel state, Nigeria. PMID- 3344316 TI - Prevalence of iron deficiency and iron-deficiency anaemia in Benin. PMID- 3344317 TI - Meat inspection technology research. PMID- 3344318 TI - [Stimulation of hemopoiesis in irradiated mice using horse immunoglobulin G]. AB - The injection of heterologous polyclonal immunoglobulin G promotes the recovery of CFUs pool and increases the amount of myelokaryocytes in irradiated mice, while in nonirradiated mice, it activates differentiation of bone marrow CFUs and enhances their migration. PMID- 3344319 TI - [Mechanism of the antimutagenic action of dibunol]. AB - In experiments with cultured V-79 Chinese hamster cells a study was made of the influence of dibunol on the level of gamma-radiation-induced micronuclei and sedimentation properties of cell nucleoids during ultracentrifugation in a neutral sucrose gradient. Protection of DNA molecule against the effects of both primary and secondary damages was found to be involved in the mechanism of the protective action of dibunol. PMID- 3344321 TI - [Sorption of bacteria by blood cells as an indicator of the reaction of animals to the action of different doses of gamma rays]. AB - In experiments with mice, guinea pigs, and dogs, a study was made of the sorptive capacity of peripheral blood cells after different gamma-radiation doses with reference to living Escherichia coli cells. The sorptive capacity of blood cells was inhibited in exposed animals the inhibition being maximum during the first 3 days following irradiation. Homologous immunoglobulin administered to mice 24 h before irradiation prevented the diminution of the sorptive capacity of cells and stimulated it during the first week following irradiation. PMID- 3344322 TI - [Changes in the activity and conditioned-reflex behavior of white rats during and after chronic microwave irradiation]. AB - Albino rats were exposed to chronic (1-3 months) electromagnetic radiation (2375 MHz; 1, 5, 10, 50 and 500 microW/cm2; 7 hours a day). Inhibition of the activity during the open field tests and diminution of consolidation of the defence conditioned reflexes in a shuttle chamber occurred during exposure (5 to 500 microW/cm2) while the activity increased and reflexes consolidation gradually normalized during the post-irradiation period. PMID- 3344320 TI - [Radioprotective action of a GGS-10 gaseous hypoxic mixture on the DNA supramolecular complex of normal tissues and sarcoma 45 of rats]. AB - Gas hypoxic mixture (GHM-10) inhaled by rats during gamma-irradiation (2 to 20 Gy) effectively protects the supramolecular complex of DNA (SC DNA) in bone marrow and spleen, but fails to protect this complex in sarcoma 45. GHM-10 itself has been shown to induce rapid and prolonged, but irreversible, decrease in SC DNA elastic viscosity in normal tissues. PMID- 3344323 TI - [Role of 5-bromodeoxyuridine in the formation of sister chromatid exchanges in human lymphocytes exposed to gamma-irradiation at the presynthetic stage of the mitotic cycle]. AB - The formation of SCE was studied in human lymphocytes irradiated at the presynthetic stage of the cell cycle in the presence or absence of 5 bromodeoxyuridine. The results obtained showed that 5-bromodeoxyuridine present in the culture medium at the time of exposure or during the postirradiation period increased the yield of SCE. It is suggested that 5-bromodeoxyuridine exerts its effect through interfering with DNA repair. PMID- 3344324 TI - [Comparison of the radiosensitizing action of metronidazole administered orally and locally]. AB - A local injection of metronidazole dissolved in dimethylsulfoxide reinforces the damaging effect of ionizing radiation on RL-67 adenocarcinoma cells to the same degree as was observed after oral administration thereof. However, with local administration, the dose of the preparation may be 12.5 times reduced. PMID- 3344325 TI - [Structural and functional changes in spinal cord neurons following low-intensity laser irradiation]. AB - In acute experiments with cats the dynamics of changes in the evoked activity of spinal neurons was determined during low-intensity laser irradiation of the cord. With histological preparations, in conditions of automatic processing of the morphometrical information, the data were obtained indicating the decrease in the post-impulse synaptic depression accompanied by the intensification of the nuclear plasmic exchange of the exposed neurons. PMID- 3344326 TI - [Effect of oxygen on gamma-radiation damage to nucleic acids irradiated in media with different pH values]. AB - The injury to DNA and RNA exposed to gamma-radiation in media of varying acidity with oxygen present or absent therein has been investigated. The interaction of the protonated base with a superoxide radical has been shown to contribute markedly to the oxygen effect of the radiation injury to nucleic acids. PMID- 3344327 TI - [Effect of low doses of ionizing radiation on the kinetics of growth of a population of HeLa tumor cells]. AB - While studying the effect of 0.1 Gy radiation on the growth of HeLa cells the authors have revealed an increase in the share of cells with the increased proliferative activity that cannot transfer to the resting state. PMID- 3344328 TI - [Systems approach to modeling radiobiological effects]. AB - Basic principles of the systemic approach to modelling of the radiobiological effects at different levels of cell organization have been formulated. The methodology is proposed for theoretical modelling of the effects at these levels. PMID- 3344329 TI - [Radiosensitivity of stem cells in the spermatogenic epithelium of mice of different strains and different ages]. AB - In experiments on CBA and BALB/c male mice (3 months of age) and F1(CBA X C57BL/6) hybrids (at the age of 3, 12, and 24 months) a difference was noted in the radiosensitivity of spermatogenic epithelium stem cells displayed by the changes in their colony-forming ability in testicular tubules 42 days following local 60Co-gamma-irradiation. The older the hybrid mice the smaller was the number of spermatogenic epithelium stem cells. PMID- 3344330 TI - [Radiobiology of stem cells in intestinal epithelium. Effect of single and multiple preliminary sublethal irradiation of mice on the dose dependence of the survival of stem cells in small intestine epithelium]. AB - After a single or three-fold whole body irradiation of mice with a dose of 4 Gy and the time interval for the proliferation to be restored (5 days or 3 weeks) the survival curve for stem cells of small intestine epithelium with regard to radiation dose was the same as that for non-preirradiated mice. This indicated that the proliferative potential of stem cells in these experimental conditions was not reduced. PMID- 3344331 TI - [Number of hematopoietic stem cells in mice in the phase of increased radiation resistance following sublethal irradiation and change in their number after repeated exposure to radiation]. AB - The content of haemopoietic stem cells in mice at the stage of the enhanced radioresistance (day 12 after irradiation with a sublethal dose of 2.75 Gy) was lower than that in the controls. Their repopulation in the repeatedly exposed mice was more intensive than in the intact mice irradiated with the same dose. The authors discuss the significance of the peculiarities observed in understanding the causes of the increase in radioresistance after sublethal irradiation. PMID- 3344332 TI - [Effect of lipid hydroperoxides on the yield of chromosome aberrations in irradiated cells]. AB - The combined effect of linoleic acid hydroperoxide and gamma-radiation on Ehrlich ascites tumor cells was not additive with regard to the formation of chromosome aberrations. When cells were preincubated in the presence of a subliminal hydroperoxide dose of 2.10(-5) M the number of aberrant cells increased after irradiation. PMID- 3344333 TI - [Prolongation of occult damage to the liver after cessation of chronic gamma irradiation]. AB - A study was made of the effect of continuous gamma-irradiation on changes in the mitotic index (MI), the ratio of the number of metaphases to that of prophases (M/P), and the frequency of chromosome aberrations at the post-metaphase in the regeneration rat liver. The data obtained indicate that the injury to the intact liver of exposed rats persists throughout the entire period of observation which is displayed by a relative stability of M/P ratio and the frequency of chromosome aberrations. On the other hand, the MI changes indicate the trend toward the repair of the injury. PMID- 3344334 TI - [Effect of x-rays on the pacemaker neurons of Helix pomatia]. AB - The effect of superlethal doses of ionizing radiation on exciting and electrical properties of giant neurons of the central nervous system of Helix pomatia has been investigated. At early times following irradiation the excitability does not significantly change whereas the membrane potential, resistance and pump-induced hyperpolarization increase. At later times, a stabilization of these parameters is followed by a diminution of resistance, a decrease of membrane potential and pump-induced hyperpolarization, and even the neuron death. PMID- 3344335 TI - [Effect of ionizing radiation on the functional state of Helix pomatia neurons. Glucose metabolism and ATP levels]. AB - The ATP level in nerve ganglia of Helix pomatia was shown to decrease 15 and 30 min, and 1 and 3 h following irradiation (5.16 C/kg). The decrease was maximum in 60 min. The absorption and utilization of glucose via a pentose-phosphate route and in the Krebs cycle did not substantially change. It is concluded that the energy supply of nerve cells under study is not responsible for the decrease in the ATP level. PMID- 3344336 TI - [Effect of ionizing radiation on the functional state of Helix pomatia neurons. The systems of Na+ and K+ transport]. AB - The influence of ionizing radiation (5.16 C/kg) on passive and active Na+ and K+ transfer within the giant neurons of edible snail (Helix pomatia) has been investigated. It has been shown that ionizing radiation increases passive permeability of membranes, inhibits active ion transport, changes the number and the affinity of functionally active Na+,K+-ATPase molecules. The authors discuss the mechanisms of action of ionizing radiation. PMID- 3344337 TI - [Polyploidization of rat hepatocytes due to cell fusion caused by radiations of different LET]. AB - The method of flow cytometry was used to study polyploidization of hepatocytes following X-, gamma-, and neutron-irradiation. Ionizing radiation was shown to induce cell polyploidization by two different ways: (1) cells and nuclei fusion, and (2) restriction of mitosis after DNA replication. RBE of 14 MeV neutrons with respect to fusion was about 5.10(3). With neutron irradiation, the sensitivity of cells by fusion was not lower than that by chromosome mutations. PMID- 3344339 TI - [Yield of sister chromatid exchanges and survival of V79-4 Chinese hamster cells irradiated with 0.7 MeV neutrons]. AB - The dependence of the survival rate and the number of sister chromatid exchanges (SCEs) in Chinese hamster V79-4 cells on the dose of gamma-rays and neutrons with average energy of 0.7 MeV has been investigated. The value of RBE for neutrons is 5.5. The number of SCEs increased with the dose of gamma-radiation while no induction of SCEs could be detected after neutron irradiation. PMID- 3344338 TI - [Long-term consequences of the effect of ionizing radiation of different LET. Relation of changes in the intensity of light scattering by blood lymphocytes in the early postradiation stages to the prolongation of the life of rats]. AB - Optic properties of rat blood were studied 24 h following gamma- or gamma-neutron irradiation with different doses. A comparative analysis of the changes observed was performed in relation to life span of animals. It is concluded that remote effects of radiation can be prognosticated by changes in light scattering of the peripheral blood lymphocytes 24 h following irradiation. PMID- 3344341 TI - [Effect of low-dose gamma-irradiation of silkworm eggs on the development of the mulberry silkworm (Bombyx mori L.)]. AB - Chronic gamma-irradiation of an egg at a dose-rate 100, 1000 and 4000 times as high as that of the natural radiation background significantly accelerates the development of Bombyx mori L. The caterpillar development may also be stimulated by a single exposure of the egg to 2 Gy radiation. The acceleration of the caterpillar growth promotes the increase in the cocoon weight and the raw-silk mass. PMID- 3344340 TI - [Synthesis of lipids in the thymus of irradiated rats]. AB - Changes in the synthesis of total lipids from 14C-glucose and 3H2O and in triacylglycerol concentration in the thymus of rats X-irradiated with a single dose of 14.35 or 6.0 Gy were investigated. Both lipid synthesis and TAG concentration were found to increase in the irradiated rat thymus. PMID- 3344342 TI - [Effect of the new x-ray ordinance on x-ray diagnosis]. AB - A report is made on the new German X-ray regulations that come into force on 1 January 1988 and their effect on X-ray diagnostics. The main points of the new regulations are constant quality control in order to decrease exposure to radiation, an improvement in image quality, and the introduction of new dose limitations for occupational exposure. PMID- 3344343 TI - [The new x-ray ordinance]. AB - The new ordinance on X-ray irradiation, which was passed on 8 January 1987 and comes into force on 1 January 1988, is designed to keep radiation exposure during X-ray examinations to the minimum absolutely necessary. This is to be achieved not only by improving the specialist qualifications of the personnel concerned, but also by improved quality control. Substantial changes in X-ray diagnosis procedures will be introduced with the expected guidelines on implementation of the new decree. PMID- 3344344 TI - [Pulmonary reaction to radiation following mantle-field irradiation. Comparison of follow-up by conventional x-ray and by computed tomography]. AB - A group of 36 patients who received mantle field irradiation for Hodgkin's disease (35 pts) or non-Hodgkin lymphoma (1 pt) were prospectively examined by plain film radiography and computed tomography (CT) for evaluation of the pulmonary reaction at the beginning and the end of the course of irradiation, and at 12 weeks, 17 weeks, and 37 weeks after the start of the mantle field irradiation. A total of 173 plain chest radiographs (p.a. and lateral view), and 167 CTs were reviewed. As in chest radiography, the pulmonary reaction to radiation seen in CT took a characteristic course with different distinguishable stages. The radiation-induced changes typically seen on on CT were reducible to three basic patterns of opacification, which sometimes appeared in combination, and had a characteristic spatial distribution. Comparison of the two imaging modalities suggest that CT should be used in special cases, while conventional plain film radiography of the chest, with the possibility of short-term controls, is still the mainstay of follow-up for patients with Hodgkin's disease. PMID- 3344345 TI - [Role of microsurgically revascularized flaps in the treatment of radionecrosis of the mandible]. AB - In spite of advances in radiation therapy of malignant tumours, osteoradionecrosis cannot always be prevented. This form of therapy causes problems particularly in reconstruction of the mandible. Seven cases are presented, and the advantages of microsurgically revascularized tissue transfer (over other methods of treatment) are pointed out and discussed. PMID- 3344346 TI - [Leiomyosarcoma of the splenic vein]. AB - The differential diagnosis of disease processes of the pancreatic tail involves considerable difficulty, despite the use of sonography, computed tomography and endoscopic retrograde cholangio-pancreatography. In most cases, morphological changes are due to pancreatic tumors, inflammatory disease or lymphoma. We report on a case of leiomyosarcoma of the splenic vein with local invasion of the pancreatic tail simulating a pancreatic tumor. PMID- 3344347 TI - [The dorsofibular process at the head of the 1st metatarsal, an osseous variant]. AB - A variant sometimes seen is an osseous process, for which there is no set shape, at the dorsofibular edge of the 1st metatarsal head. Such processes more than 5 mm in length occur in about 10% of adults. This osseous variant also remains recognizable when arthritic spurs are present in addition. PMID- 3344349 TI - Doctor called after crowning: $8.3 million award. PMID- 3344348 TI - [Quality assurance in x-ray diagnosis as specified in DIN 6868]. AB - Regular quality control and safety assurance in diagnostic radiological systems are included in the new radiation protection regulations. The monitoring program for both the equipment and the film processor can enable the user to recognize loss of quality early. Variables in the film processing unit can be differentiated from faults in the X-ray equipment more easily, including its use. The cost and time spent in setting up a safety assurance program are justified by the increase in quality. PMID- 3344350 TI - Intentional & unintentional acts: malpractice. Case in point: Cudges v. Our Lady of Lourdes Hosp. (514 So. 2d 195--LA). PMID- 3344351 TI - Anal margin carcinoma: 21 cases treated at the Institut Curie by exclusive conservative radiotherapy. AB - Between 1962 and 1980, 21 patients with anal margin carcinoma were treated with exclusive radiotherapy. They were divided into 4 T1, 7 T2, 8 T3 and 2 T4 cases; only 3 cases presented with an N1 lymph node involvement (1 T2 and 2 T3). The tumor dose was 65 Gy in 22 fractions and 55 days; the inguinal dose was 50 Gy in 15 sessions and 50 days for prophylactic irradiation performed in 9/18 N0 patients, and 65 Gy with a limited 15 Gy boost for the 3 N1 cases. The results are: for T1, 4 patients alive and well out of 4; for T2, 3 out of 7; for T3, 2 out of 8; for T4, 2 out of 2. The overall survival was 11 out of 21 after 5 years. Severe complications occurred in 2 patients out of 21. Sphincter preservation was obtained in 9 patients out of 10 cured cases. PMID- 3344352 TI - Magnetic resonance imaging and high-resolution computed tomography in tumors of the lung and the mediastinum. AB - Magnetic resonance (MR) imaging and high resolution computed tomography (CT) have been compared in 37 patients who had expansive processes of the lung and the mediastinum. MR imaging and CT scanning gave identical results in 32 patients; in 5 patients, CT scanning has proved more useful in evaluating the stag e of primary lung tumors. MR imaging often gives more information about the actual size of the tumor, and the involvement of close structures, although it does not modify staging of the tumor. MR imaging has the advantage to differentiate hilar adenopathy from blood vessel structures. Evaluation of T2 relaxing time (that we have performed in the same location of thin-needle biopsy aspiration), however, did not prove to be of diagnostic significance; this indicates that MR imaging at the moment is not suitable for tissue typification. PMID- 3344353 TI - Plastic material used to optimize radiotherapy of head and neck tumors and the mammary carcinoma. AB - In order to improve head and neck tumor therapy, face masks were developed. The physical and mechanical properties of 11 apparently suitable materials were tested using a phantom. According to our studies "HEXCELITE" (supplied by Medimex, Hamburg, F.R.G.) proved to be the best material. Plastic breast molds were made to optimize the dose distribution for radiation therapy with fast electrons of post-mastectomy breast tumors. Here too the mechanical and physical properties of nine different materials were tested. The most suitable of these proved to be the gel mat "PRIMAMED" (supplied by Schulke and Mayr, Norderstedt, F.R.G.). The two materials mentioned have been well tolerated by more than 200 patients. PMID- 3344354 TI - Effects of dosimetric and clinical uncertainty on complication-free local tumor control. AB - A mathematical description is developed to demonstrate the effects of uncertainty on complication-free local tumor control. Responses of tumors and normal tissues are modeled by conventional radiobiological models. Uncertainties are considered in the delivery of absorbed dose to the target volume and the normal tissue at risk for complications. The degree by which uncertainties compromise complication free local control for target volumes with various tumor cell burdens is calculated. PMID- 3344355 TI - Repair and recovery in the epithelial and vascular connective tissues of pig skin after irradiation. AB - Using split-dose experiments, with varying time intervals between two equal fractions, the total repair capacity and the time of onset of additional recovery was determined for both early and late responses in pig skin. The early epidermal response was studied after beta-irradiation and 250 kV X-rays were used to investigate dermal changes. Based on the results of seven separate single dose studies the ED50 value ( +/- SE) for early moist desquamation was 27.76 +/- 0.91 Gy. With intervals of one and 14 days between two equal fractions similar ED50 values of 35 Gy were obtained. This suggested a recovered dose of approximately 7 Gy for epithelial desquamation, a repair capacity for sublethal injury of 20-25%. Additional recovery possibly due to repopulation, was observed with intervals of greater than or equal to 21 days between fractions. The rate of additional recovery was linearly related to the time interval between doses and was equivalent to 74 cGy/day. Recovery from the first dose was complete within 6 weeks. Evidence for radiation-induced tissue hypoxia was obtained when longer time intervals between doses were used. The more subjective early erythema reaction was also assessed. This reaction produced a similar estimate for the repair capacity and for the time of onset of recovery to that obtained using moist desquamation. This agreement was not maintained with intervals of greater than or equal to 28 days between doses due to an artefact associated with the way erythema reactions were assessed. After irradiation with single doses of X-rays ED50 values of 18.59 +/- 0.49 and 20.53 +/- 0.35 Gy were obtained for the dermal reactions of dusky/mauve erythema and necrosis, respectively. The recovered doses for the dermal responses, with intervals of 1 and 28 days between fractions, were similar, approximately 4.2 Gy, indicating a total repair capacity of 20-25%. Additional dermal recovery was seen only with intervals of greater than 28 days between doses. There was no evidence for "slow repair". Surprisingly complete recovery from the first dose was suggested with an interval of 16 weeks between doses. This finding might be influenced by radiation-induced hypoxia. The time of onset of additional repopulation/recovery and the latency for tissue impairment in epidermal and dermal tissues in pig skin were compared with those for other early and late responding tissues. PMID- 3344356 TI - Lack of protection by oestrogen from radiation-induced testicular damage in the rat. AB - The influence of pretreatment with oestradiol dipropionate (E) on the response of the rat testis to radiation has been studied. Treatment of rats for 3 weeks with E (100 mg/kg per week) induced severe atrophy of the testis. At this time, the testes were locally irradiated to doses of 0, 4 or 15 Gy, E treatment was continued for a further week and the rats were killed 24 or 36 weeks later. Radiation alone had a marked effect on spermatogenesis as assessed by testicular weight and counts of regenerating tubule cross-sections. At 24 weeks, 8% of cross sections were found to possess spermatogenic cells after 4 Gy and this had increased to 15% at 36 weeks. No significant regeneration was observed after 15 Gy. Similar results were obtained in those rats pretreated with E. Following irradiation alone, decreases in interstitial cell numbers and testicular luteinizing hormone (LH) receptors reflected Leydig cell damage. Again, pretreatment with oestrogen did not appear to reduce Leydig cell damage. The results of the present study suggest that pretreatment with oestrogen is not able to reduce the testicular damage induced by moderate to high single doses of radiation. PMID- 3344357 TI - [Double pylorus: a new case]. PMID- 3344358 TI - [Endoscopic fistulotomy in bile duct diseases]. PMID- 3344359 TI - [Extracorporeal shock wave lithotripsy of gallstones. Methods, results and perspectives]. PMID- 3344360 TI - [Drug-induced fevers]. PMID- 3344361 TI - [Regional spinal anesthesia in intensive care and in anesthesia]. PMID- 3344362 TI - [Cranial giant meningiomas with minimal symptoms: experiences in 275 cases]. PMID- 3344363 TI - [Anthroposophically expanded holistic health and carcinogenesis. Documentation No. 9]. PMID- 3344364 TI - [Urticaria due to an intrauterine device]. PMID- 3344365 TI - [A case from practice (101). Patient: Mrs. C.R., born 1959, nurses' aide]. PMID- 3344366 TI - [Cardiac pain or esophageal pain?]. PMID- 3344367 TI - [Lupus erythematosus (SLE), pneumopathy and fever]. PMID- 3344368 TI - [Chest pains, sweating, dyspnea and cough]. PMID- 3344369 TI - [A case from practice (102). Patient: Mr. S.S., born 5-13-1926, business clerk]. PMID- 3344370 TI - [Morphine: new ways of administration in the treatment of cancer pain]. PMID- 3344371 TI - [Horton's disease]. PMID- 3344372 TI - [Resistant depressions]. PMID- 3344373 TI - [Sudden infant death]. PMID- 3344374 TI - [Biological rhythms]. PMID- 3344375 TI - It's time we started taking care of our own. PMID- 3344376 TI - Is going back to school your best move? PMID- 3344377 TI - It can't be wrong to care "too much". PMID- 3344379 TI - There's just no excuse for i.v. complications. PMID- 3344378 TI - Special care for skeletal traction. PMID- 3344380 TI - Doctors are S.O.B.s. PMID- 3344382 TI - Getting the kinks out of a bladder drainage system. PMID- 3344381 TI - Are you ready for this bedside emergency? Massive bleeding. PMID- 3344383 TI - When dental care is up to you. PMID- 3344384 TI - In search of the hospital that suits your career. PMID- 3344385 TI - Epilepsy: putting the patient back in control (continuing education credit). PMID- 3344386 TI - Controlling epilepsy with surgery. PMID- 3344387 TI - Obtaining a seizure history--discovering a pattern. PMID- 3344388 TI - What hospitals must tell you about work hazards. PMID- 3344390 TI - Now newborns can stay home for phototherapy. PMID- 3344391 TI - Keeping pin sites problem-free. PMID- 3344389 TI - Meeting your Ca patient's nutritional needs. PMID- 3344393 TI - [Diagnosis and prevention of hepatitis B virus infections: applied example of genetic recombinations]. PMID- 3344392 TI - [Prenatal diagnosis]. PMID- 3344394 TI - [Vaccines obtained by genetic engineering]. PMID- 3344395 TI - The predictive value of antimitochondrial antibodies in establishing the diagnosis of primary biliary cirrhosis. AB - Primary biliary cirrhosis (PBC) was diagnosed in 85% of patients with antimitochondrial antibodies (AMA) found in sera routinely analyzed for autoantibodies. In these patients and in those without PBC other autoimmune disorders were common, but the latter patients generally had a low AMA titer, 1:80 or less. It was concluded that a low AMA titer may occur in many patients without PBC. On the other hand, it appears very likely that PBC is present in patients with an AMA titer exceeding 1:80 and an increased activity of alkaline phosphatases without signs of extrahepatic biliary obstruction. PMID- 3344396 TI - Evaluation of the applicability of the SeHCAT test in the investigation of patients with diarrhoea. AB - For the assessment of ileal bile acid conservation the retention of orally administered 75Se-23-selena-25-homotaurocholic acid (SeHCAT), a gamma-ray emitting radioisotope-labelled synthetic bile acid, was measured by an uncollimated abdominal gamma camera in 89 patients with various gastrointestinal disorders and in 20 persons without gastrointestinal complaints. A significant differences in retention was observed between patients with and without previously detected ileal disease. However, it was not possible by use of the test to differentiate between the various types of diarrhoea. Hence the test is not recommended in the routine investigation of patients with diarrhoea. PMID- 3344397 TI - Plasma lathosterol and campesterol in detection of ileal dysfunction. AB - Plasma lathosterol levels reflect cholesterol synthesis, especially that induced by bile acid malabsorption, whereas plasma plant sterol contents change in parallel with cholesterol and fat absorption. The significance of lathosterols and plant sterols (campesterol and sitosterol) was therefore studied in detection of ileal dysfunction in 29 patients with ileal resection (7 with no malabsorption, 8 with only bile acid malabsorption, and 15 with bile acid, fat, and cholesterol malabsorption) and in 8 jejunoileal bypass patients with fat, bile acid, and cholesterol malabsorption. Ileal dysfunction-induced faecal loss of bile acids was proportionate to cholesterol synthesis, which, in turn, was proportionate to the plasma levels of lathosterols, so that the lathosterols contents were also closely correlated (r = 0.880) to faecal bile acids. The lower the cholesterol absorption, the lower was the plasma campesterol (less consistently, beta-sitosterol) level and the higher the faecal fat. Thus, elevated plasma lathosterol content is highly suggestive of bile acid malabsorption in a patient with suspected ileal dysfunction. High plasma content of lathosterols combined with a low campesterol level points to associated fat malabsorption, indicating that the lathosterol to campesterol ratio in plasma is frequently increased in patients with ileal dysfunction associated with steatorrhoea. PMID- 3344398 TI - Experimental pancreatography: a comparison of three contrast media. AB - Twenty-five piglets were subjected to experimental transduodenal pancreatography, using three contrast media (CM), namely sodium meglumine diatrizoate (Urografin), meglumine ioxaglate (Hexabrix), and iohexol (Omnipaque), all diluted to a concentration of 300 mg/ml of iodine. The emptying of CM from pancreatic ducts was studied by repeated roentgenograms, and pancreatic irritation by serum amylase and phospholipase A2 measurements. On the 3rd day after pancreatography the glands were removed for histologic examination of tissue damage. Hyperamylasaemia was seen in 53% of the animals 12 to 15 h after examination, to equal extents in each group. Minimal acinar destruction was seen on histologic examination in all cases. The changes were least when diatrizoate was used. The difference from the changes seen in the ioxaglate group was significant (p less than 0.05). Emptying of CM from the ducts was highly significantly (p less than 0.001) faster in the diatrizoate group than in the other groups. Rapid emptying may be an advantage in clinical endoscopic retrograde pancreaticocholangiography. PMID- 3344399 TI - Supposed coeliac disease during childhood and its presentation 14-38 years later. AB - Thirty-five subjects treated with a gluten-free diet for a chronic gastrointestinal disorder (no biopsy performed) in early childhood were re examined 14-38 (median, 28) years later. Twenty-one accepted jejunal biopsy at re examination. None of those studied were on a gluten-free diet at the time of the study. Ten of 21 biopsy specimens were abnormal--6 with flat mucosa and very low disaccharidase levels, indicating coeliac disease, and 4 with low disaccharidase activity but morphologically normal mucosa. Three of the six subjects with flat mucosa showed a slight fat and lactose malabsorption, but their clinical condition did not suggest serious intestinal disease. Ingestion of gluten throughout most of childhood did not appear to affect growth, as evaluated by final height. Jejunal biopsy is recommended in all patients with gastrointestinal symptoms that are not otherwise explainable if their medical history shows a period of gluten-free diet for a chronic gastrointestinal disorder in childhood. PMID- 3344400 TI - Interdigestive motility and motilin in hypophysectomized patients. AB - Basal fluctuations of motilin and their correlation to intestinal motor activity were studied in five hypophysectomized (anterior lobe resection) patients. A cyclic pattern of motor activity identical to the one described in normal volunteers was observed. The mean interval between two activity fronts (AF) was 115 min, which is not significantly different from the normal length. Motilin levels were within the normal range, and fluctuations correlated with the occurrence of an AF. The mean difference between motilin levels 15 min before the AF and at the time of the start of the AF was +15 pM (P less than 0.05). For the levels 15 min after the AF the mean difference was -9 pM (P less than 0.05). These values correlate well with those reported by us in normal volunteers, in whom the mean differences were +11 pM and -14 pM, respectively. It is concluded that the adenohypophysis is not involved in the regulation of motilin levels or in the regulation of interdigestive motility in man. PMID- 3344401 TI - The time pattern of gastroesophageal reflux. AB - The variations in gastroesophageal reflux over 24 h were analyzed in 220 patients with symptoms suggestive of gastroesophageal reflux disease and in 50 normal subjects by studying the results obtained by ambulatory 24-h esophageal pH monitoring. Three time periods, differing in amount of reflux, were identified: daytime (0700-1700 h), evening (1700-2400 h), and night (2400-0700 h). The greatest amount of reflux was seen during the evening period. This pattern was not solely due to increase in reflux postprandially, since it persisted even after the elimination of postprandial reflux. The pattern was most pronounced in patients with esophagitis. The pressure of the distal esophageal high-pressure zone was measured at 0800 h, at noon, and at 1600 h during one day in another 10 patients. The pressure was significantly lower at 1600 h than at 0800 h and at noon, providing a possible explanation for the changes seen in gastroesophageal reflux. We have described a time pattern of gastroesophageal reflux that has important implications for the design of medical therapy in different groups of patients. PMID- 3344402 TI - Incomplete distal denervation and recurrent ulcer after parietal cell vagotomy. AB - Twenty-five patients with chronic duodenal ulcer and subjected to parietal cell vagotomy were evaluated as either underdenervated or optimally denervated, depending on whether parietal cells were present distal to the last branch of Latarjet's nerve. A 5-year follow-up study demonstrated recurrent ulcer in three of five judged as underdenervated. In addition to the possible technical error of distal and proximal dissection, the importance of the inborn error of incomplete distal denervation is confirmed. PMID- 3344403 TI - Beta-glucuronidase activity related to bacterial growth in common bile duct bile in gallstone patients. AB - Beta-glucuronidase activity in the bile may be of importance in the etiology of pigment gallstones. This enzyme is of hepatic or bacterial origin. We have described a method to measure the activity of bacterial beta-glucuronidase in human bile, using 4-nitrophenyl-beta-D-glucopyranosiduronic acid as substrate. The method was used to measure the beta-glucuronidase activity in the bile from 51 patients with gallstone disease. This activity was related to the presence of beta-glucuronidase-producing bacteria in the bile. Escherichia coli, Bacteroides species, and Clostridium perfringens were the only species found to produce beta glucuronidase. Patients with beta-glucuronidase-producing bacteria had on an average significantly higher enzyme activity in the bile than patients without such bacteria (p less than 0.01). The limitations of using artificial substrates in this type of studies are discussed. PMID- 3344404 TI - 24-hour oesophageal two-level pH monitoring in healthy children and adolescents. AB - Two-level pH recording in the oesophagus was performed for 24 h in 28 healthy schoolchildren between 9.3 and 17.3 years of age, to obtain reference values for reflux studies. The pH probes were placed 5 and 15 cm above the lower oesophageal sphincter by means of the manometric technique. A standardized acid-free diet was given on the day of recording. A drop in pH to 4.0 or below was regarded as reflux. The normal upper limit of total reflux time was 1.0% at the lower oesophageal level. Mean reflux time was about three times shorter at the upper level than at the lower, which indicates the importance of exact positioning of the pH probe. PMID- 3344405 TI - [So-called "renal" idiopathic hypercalciuria most often has a dietary origin]. AB - Among renal stone formers with idiopathic hypercalciuria, patients who remain hypercalciuric despite low calcium intake have often been regarded as having a primary renal leak of calcium, i.e. renal hypercalciuria. However, at any given intake of calcium, dietary factors other than calcium can generate hypercalciuria, e.g. high intakes of sodium, of animal protein or of carbohydrates, or obesity itself. Thus, the incidence of renal hypercalciuria among stone formers has probably been overestimated. To address this issue, the aforementioned dietary and/or metabolic factors have been evaluated in 51 stone formers with idiopathic hypercalciuria refractory (i.e. U-Ca. V greater than 250 mg/24 h) to 5 days on low calcium intake (max. 400 mg/day). In 15 patients (all had U-Na. V greater than 200 mmol/24 h), U-Ca.V was within the 95% confidence limits of a nomogram U-Ca.V versus U-Na.V, suggesting that their idiopathic hypercalciuria was related, at least in part, to the high sodium intake. 7 patients had severe hyperuricosuria (greater than 1 g/24 h) suggesting high animal protein intake. 20 patients were obese (greater than 120% ideal weight) with (7 cases) or without (13 cases) concomitant fasting hyperinsulinemia (greater than 18 microU/ml). In addition, a careful retrospective analysis of intravenous pyelograms disclosed medullary sponge kidneys in 8 cases which had remained undiagnosed so far; in one of them histological confirmation was obtained after surgical removal of a renal pole and a radiologico-histological comparison. Thus, only 14 out of 51 patients had an otherwise unexplained idiopathic hypercalciuria on low calcium intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344406 TI - [Psychological findings in alleged phlebologic disorders of the leg]. AB - Twenty-six female patients with restless legs underwent psychiatric investigation as part of a pilot study. Most exhibited a depressive-anxious-hypochondric syndrome. The development of physical symptoms in connection with psychic disturbances and the treatment of patients with restless legs are discussed. PMID- 3344407 TI - [A Candida krusei epidemic in a hematology department]. AB - Candida krusei is a rarely isolated opportunistic yeast which we observed in 12 immunocompromised patients over a four-month period. Epidemiologic investigations identified the source of the organism in a bottle containing contaminated lemon juice in the hospital kitchen. Since elimination of the source we found the yeast in only 3 additional cases (4% vs. 0.4% of all patients with positive yeast cultures) over 11 months. Upper respiratory tract was the most common site of colonization. 6 of 15 patients developed infections with C. krusei (4 pneumonia, 1 disseminated infection and 1 localized). 4 died from fungal infections. - The importance of infection control institutions for efficient epidemiologic investigation of nosocomial infections is discussed. PMID- 3344408 TI - [Predictive potential of positive values in the latex agglutination test for Candida antigen (Cand-Tec)]. AB - The correlation of Cand-Tec (candida antigen detection) with clinical findings and results in passive hemagglutination and immunoelectrophoresis (antibody detection) has been evaluated retrospectively. Based on mycological findings, 33 patients with a Cand-Tec titer were classified into five groups. Systemic antimycotic therapy was another criterion. Using a titer of greater than or equal to 1:8 as diagnostic of systemic or local candidal infection, the positive predictive value was 33% and 55% respectively. However, a titer of greater than or equal to 1:8 correlated significantly (p less than 0.05) with infection (systemic, presumably systemic and local candidiasis, n = 3). The combined findings of an antigen titer of greater than or equal to 1:8 and antibodies to cytoplasmatic protein antigens of candida correlated even better with infection (p less than 0.02) and had a positive predictive value of 100%. Antigen and antibody determination may be useful adjunctive procedures in the diagnosis of candida infections. PMID- 3344409 TI - [Idiopathic cold agglutinin disease. Clinical aspects, therapy and course in 6 patients]. AB - Clinical features, diagnostic procedure, therapy, course of the disease and prognosis in 6 patients with severe idiopathic chronic cold agglutinin disease are described. In 5 patients the main complaint was cold mediated acrocyanosis. The cold agglutinin in all patients was of anti-I type and belonged to IgM immunoglobulin. Keeping warm provided symptomatic relief and the hemolysis decreased to a milder form. Treatment with glucocorticoids alone failed in two patients but succeeded in combination with chlorambucil or cyclophosphamid. One patient developed a lymphoproliferative disorder 11 years after diagnosis of idiopathic chronic cold agglutinin disease. PMID- 3344411 TI - [Treatment of neoplastic hypercalcemia using single-infusion diphosphonate]. AB - 40 patients with malignant hypercalcemia were treated with a single dose of APD, a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose response in man, the patients were divided into four groups receiving 30, 45, 60 or 90 mg respectively as 24-hour infusion. Initial plasma calcium was similar in all groups except that receiving 90 mg, some of whose patients had higher initial values. All patients responded to APD with a rapid decrease of plasma calcium concentration from 3.44 +/- 0.10 mmol/l at day 0 to 2.33 +/- 0.06 at day 6, p less than 0.001). Plasma calcium became normal within 4 to 6 days in all patients but 6, all from the group receiving the low doses of APD (30 or 45 mg). Slight and asymptomatic hypocalcemia occurred in only 2 patients of the low dose groups, but in 6 of the high dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 2 months in 6 patients of group 30 mg, in 5 patients of group 45 mg, in 1 patient of group 60 mg and in 2 patients of group 90 mg, whereas mortality was almost identical in the 4 groups. When retreated with a single dose of APD, all patients again showed normalization of calcemia. In all groups plasma phosphate, plasma creatinine and urinary calcium excretion decreased significantly. Clinical improvement was observed in all patients, with minimal side effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344412 TI - [Hepatic manifestations of the acquired immunodeficiency syndrome (AIDS)]. AB - Hepatic manifestations of acquired immunodeficiency syndrome (AIDS) were analyzed in 76 consecutive patients. Serological markers of hepatitis B were found in 84%. All instances of biopsy-proven chronic hepatitis were associated with delta infection. One patient with intestinal cryptosporidiosis had a severe cholestasis. In the majority of patients histological examination of the liver revealed non-specific alterations, but in several cases was diagnostic of mycobacterial disease. The study of liver disease in HIV-infected patients could lead to a better understanding of diseases such as chronic hepatitis B and sclerosing cholangitis. PMID- 3344410 TI - [Prevalence of Lyme borreliosis in a Swiss population at risk]. AB - The epidemiology of "Lyme borreliosis" in Europe and the significance of positive antibody titers against Borrelia burgdorferi is not well known. Since "orienteering", a competitive cross country sport with a map and a compass, usually in forests, elevates the risk of being bitten by ticks and infected by B. burgdorferi, nearly 1000 orienteerers were included in a prospective study. - In this population the prevalence of positive IgG-antibodies (immunofluorescence technique) was almost 20% and of IgM-antibodies 4%. However, the frequency of associated symptoms in the clinical history of the probands was very low, even in individuals with highly positive titers. - We conclude that the rate of asymptomatic Borrelia infections is high in this special group, and probably also in the general population, and that one has therefore to be cautious in interpreting an isolated positive "Lyme titer". Further investigations are needed, and, in particular, follow-up of the many "positive" subjects without clinical symptoms may be helpful in understanding this fascinating disease better. PMID- 3344413 TI - [Proximal fractures of the femur. Economic analysis of hospital treatment]. AB - The cost of hospital treatment of cervical and intertrochanteric fractures of femur is studied in 218 patients aged 70 and over, treated during 1985 in a specialized university department. Real costs show little difference from contractual prices as established by the hospital administration. They depend mainly on the length of hospital stay (a function of the type of treatment) and only indirectly on the type of fracture. The only hope of reducing costs is to shorten the number of days spent by these patients in costly university departments. The physician should therefore try to use methods of treatment that render patients rapidly independent, but the administration should provide enough rehabilitation wards and homes to admit semi-dependent patients rapidly after acute care of the fracture and of any associated pathology. PMID- 3344414 TI - [Disease course in 20 patients with an early diagnosis of phenylketonuria and hyperphenylalaninemia]. AB - Twenty patients with PKU or hyperphenylalaninemia at ages 0.1 to 15.6 years (median age 6.2 years) were studied prospectively. In all children the condition had been diagnosed when they were neonates on the basis of an abnormal Guthrie test. To maintain plasma phenylalanine levels between 0.2-0.5 mM, dietary restriction of phenylalanine to 20-80 mg/kg daily (median 40 mg/kg) was necessary in 14 children. In children above 8 years, however, these plasma levels were frequently exceeded. In 6 children plasma phenylalanine levels were higher than normal diet. Height, weight and head circumference were within normal range in all patients at all ages. Determinations of DQ/IQ were done at 2, 4, 6 and 8 years of age and revealed values between 90-120 with a median of 102 in the 14 patients who were tested. Only 1 patient had IQ levels between 75-85 and attended special school. Nine other patients were in grade school performing averagely or above. This study confirms that early treatment and long-term follow-up of patients with PKU yield good results. Unsolved problems include duration of dietary treatment and the management of pregnancy in women with PKU. PMID- 3344415 TI - [Extracorporeal shock wave lithotripsy (ESWL) in the treatment of bile duct stones]. AB - Ten patients with common bile duct stones not removable by endoscopic measures after sphincterotomy were treated by extracorporeally generated shock waves. In 9 patients stones up to 30 mm in diameter were disintegrated. Two patients became free of stone fragments spontaneously within one day and in 7 patients the stone fragments were extracted endoscopically. No complications occurred. Extracorporal shock wave treatment represents a promising alternative to surgery in cases where common bile duct stones cannot be extracted endoscopically. PMID- 3344416 TI - [Morbid obesity. Our results with the appetite-depressing stomach balloon]. AB - Morbid obesity still remains a controversial topic with varied therapeutic approaches. In cases of unsuccessful conservative management we implant a gastric balloon or bubble. 30 balloons have been introduced in 24 patients with a mean age of 43 years (26-68 y.) and a mean body weight of 115 kg (87-160 kg). Mean overweight was 47 kg. The balloons were introduced immediately after gastroscopy performed to identify possible contraindications. Except in the initial 3 patients this procedure was carried out in the outpatient clinic. 25 silicon mammary prostheses were implanted until a special balloon (Ballobes-Balloon) became available for the last 5 cases. Implantation and follow-up has been uneventful in all cases. Our data suggest that a combination of this approach with close dietary management provides more efficient and rapid weight reduction than any diet alone. PMID- 3344417 TI - [Involvement of the trachea and lungs in AIDS-associated Kaposi's sarcoma]. AB - Kaposi's sarcoma is now the second most common AIDS-associated disease, Pneumocystis carinii pneumonia being the commonest. The clinical and radiological picture of bronchopulmonary Kaposi's sarcoma is often indistinguishable from that of nonspecific interstitial pneumonitis. Diagnosis of the sarcoma in the airways, and especially in the lung parenchyma, is difficult. The case of a patient with AIDS and bronchopulmonary Kaposi's sarcoma is presented and the diagnostic, therapeutic and prognostic problems are discussed. PMID- 3344418 TI - [Hydrochlorothiazide-induced lung edema with shock]. AB - We report the case of a 74-year-old woman who developed pulmonary edema and shock shortly after ingestion of one tablet of hydrochlorothiazide/amiloride. The clinical findings and course of the disease were characteristic of hydrochlorothiazide-induced pulmonary edema. 14 similar case are reported in the literature. Attention is drawn to this rare but dangerous side effect of a frequently used diuretic. PMID- 3344419 TI - [HIV transmission via blood transfusions: a study by the Swiss Red Cross blood bank service]. AB - An inquiry amongst blood transfusion services served to establish at 19 the number of known transfusion associated HIV infections in Switzerland. In 12 cases the transfusion of an anti-HIV positive blood unit could be proven retrospectively, while in 7 cases an HIV-infected blood donor could not be found but the association of the infection with blood transfusion is highly probable by exclusion of other risk factors. All these infections occurred before introduction of anti-HIV screening in Switzerland in November 1985. After this date no new transfusion associated HIV infections have been reported. It is estimated that there are fewer than 170 transfusion associated HIV infections in Switzerland. The probability of infection with AIDS by blood transfusion is less than 1:500,000. Blood transfusion today appears to be as safe as before the emergence of the AIDS epidemic. PMID- 3344420 TI - Scanning tunneling microscopy of freeze-fracture replicas of biomembranes. AB - The high resolution of the scanning tunneling microscope (STM) makes it a potentially important tool for the study of biomaterials. Biological materials can be imaged with the STM by a procedure in which fluid, nonconductive biomaterials are replaced by rigid and highly conductive freeze-fracture replicas. The three-dimensional contours of the ripple phase of dimyristoylphosphatidylcholine bilayers were imaged with unprecedented resolution with commercial STMs and standard freeze-fracture techniques. Details of the ripple amplitude, asymmetry, and configuration unobtainable by electron microscopy or x-ray diffraction can be observed relatively easily with the STM. PMID- 3344421 TI - Baltimore attacks "professional guardians of the status quo". PMID- 3344422 TI - A no-fault proposal for AIDS high risks. PMID- 3344424 TI - Schistosomiasis eradication in China. PMID- 3344423 TI - Homo photosyntheticus: reaction. PMID- 3344425 TI - The long, lost survey on sex. PMID- 3344426 TI - Pesticides to be judged on leachability. PMID- 3344428 TI - Howard Hughes establishes unit at MIT. PMID- 3344427 TI - AIDS policy in the making. PMID- 3344429 TI - EPA cancer risk assessments. PMID- 3344430 TI - A bloody battle over an anemia treatment. PMID- 3344431 TI - Article embroils JAMA in ethical controversy. PMID- 3344432 TI - Three-dimensional structure of cholera toxin penetrating a lipid membrane. AB - Two-dimensional crystals of cholera toxin bound to receptors in a lipid membrane give diffraction extending to 15 A resolution. Three-dimensional structure determination reveals a ring of five B subunits on the membrane surface, with one third of the A subunit occupying the center of the ring. The remaining mass of the A subunit appears to penetrate the hydrophobic interior of the membrane. Cleavage of a disulfide bond in the A subunit, which activates the toxin, causes a major conformational change, with the A subunit mostly exiting from the B ring. PMID- 3344433 TI - Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice. AB - A complementary DNA encoding the human low density lipoprotein (LDL) receptor under control of the mouse metallothionein-I promoter was injected into fertilized mouse eggs, and a strain of mice expressing high levels of LDL receptors was established. After administration of cadmium, these mice cleared intravenously injected 125I-labeled LDL from blood eight to ten times more rapidly than did normal mice. The plasma concentrations of apoproteins B-100 and E, the two ligands for the LDL receptor, declined by more than 90 percent after cadmium treatment, but the concentration of another apoprotein, A-I, was unaffected. Therefore, overexpression of an endocytotic receptor can dramatically lower the ambient concentration of its ligand in vivo. PMID- 3344434 TI - Generation of cDNA probes directed by amino acid sequence: cloning of urate oxidase. AB - Urate oxidase (E.C. 1.7.3.3) catalyzes the oxidation of uric acid to allantoin in most mammals except humans and certain primates. The amino-terminal amino acid sequence for porcine urate oxidase was determined and used in a novel procedure for generating complementary DNA (cDNA) probes to this amino acid sequence. The procedure is based on the polymerase chain reaction and utilizes mixed oligonucleotide primers complementary to the reverse translation products of an amino acid sequence. This rapid and simple cDNA cloning procedure is generally applicable and requires only a partial amino acid sequence. A cDNA probe developed by this procedure was used to isolate a full-length porcine urate oxidase cDNA and to demonstrate the presence of homologous genomic sequences in humans. PMID- 3344435 TI - Nicotinic antagonists enhance process outgrowth by rat retinal ganglion cells in culture. AB - Functional nicotinic cholinergic receptors are found on mammalian retinal ganglion cell neurons in culture. The neurotransmitter acetylcholine (ACh) can be detected in the medium of many of these retinal cultures, after release presumably from the choline acetyltransferase-positive amacrine cells. The postsynaptic effect of endogenous or applied ACh on the ganglion cells can be blocked with specific nicotinic antagonists. Here it is shown that within 24 hours of producing such a pharmacologic blockade, the retinal ganglion cells begin to sprout or regenerate neuronal processes. Thus, the growth-enhancing effect of nicotinic antagonists may be due to the removal of inhibition to growth by tonic levels of ACh present in the culture medium. Since there is a spontaneous leak of ACh in the intact retina, the effects of nicotinic cholinergic drugs on process outgrowth in culture may reflect a normal control mechanism for growth or regeneration of retinal ganglion cell processes that is exerted by ACh in vivo. PMID- 3344436 TI - Salivary gland lysates from the sand fly Lutzomyia longipalpis enhance Leishmania infectivity. AB - Leishmaniasis is a parasitic disease transmitted by phlebotomine sand flies. The role of sand fly saliva in transmission of the disease was investigated by injecting mice with Leishmania major parasites in the presence of homogenized salivary glands from Lutzomyia longipalpis. This procedure resulted in cutaneous lesions of Leishmania major that were routinely five to ten times as large and contained as much as 5000 times as many parasites as controls. With inocula consisting of low numbers of Leishmania major, parasites were detected at the site of injection only when the inoculum also contained salivary gland material. This enhancing effect of sand fly salivary glands on cutaneous leishmaniasis occurred with as little as 10 percent of the contents of one salivary gland of one fly. Material obtained from other bloodsucking arthropods could not mediate the phenomenon. PMID- 3344438 TI - Nuclear medicine and the environment--Part III. PMID- 3344437 TI - Neural model of adaptive hand-eye coordination for single postures. AB - A neural network model has been developed that achieves adaptive visual-motor coordination of a multijoint arm, without a teacher. The model learns to position an arm so that it reaches a cylinder arbitrarily positioned in space. The model uses a new neural architecture and a new algorithm for modifying neural connection strengths. Computer simulations show that the model performs with an average position error of 4% of the arm's length and with an average orientation error of 4 degrees. The model is designed to be generalized for coordinating any number of topographic sensory inputs with limbs of any number of joints. PMID- 3344439 TI - Nonvisualization of both kidneys with I-131 orthoiodohippurate scintigraphy. PMID- 3344440 TI - Splenic uptake in bone imaging. PMID- 3344442 TI - Head and neck cancer. PMID- 3344441 TI - Suboptimal red blood cell labeling with Tc99m. PMID- 3344443 TI - Treatment of head and neck cancer by radiation therapy. PMID- 3344445 TI - [Quality control in mammography. 1. Status check]. PMID- 3344444 TI - Psychosocial aspects of head and neck cancer. AB - The major psychosocial issues in managing the patient with a head and neck tumor are dealing with the emotional reactions to structural and functional deficits, recognizing and treating preexisting personality problems, especially those related to alcohol and tobacco abuse, which frequently complicate their treatment course. These factors influence the rehabilitation process which should begin in the preoperative period with careful attention to psychologic and social assessment and psychiatric evaluation; if an alcoholic history is elicited. Important continuity in rehabilitation can be accomplished by contact with the rehabilitative team members before surgery, preoperative chemotherapy or radiation. Attention to appropriate adaptation to facial prostheses and dealing early with communication disorders requires a specialized staff and a rehabilitative team which can call on a range of skills including a psychiatric consultant. While the ordeal of the head and neck cancer patient is psychologically difficult and challenging, most patients are able, with the proper help, to resume full and productive lives. PMID- 3344446 TI - [X-ray examination of the small bowel: conventional and Sellink enteroclysis]. PMID- 3344447 TI - [Indications, technic and results of selective arteriography of the internal iliac artery in erectile dysfunction]. PMID- 3344448 TI - Diffuse spreading Clostridium septicum infection, malignant disease and immune suppression. AB - Nineteen patients have been treated with gas gangrene infection proved on cultures to be caused by Clostridium septicum. Infection occurred after trauma in three patients and occurred spontaneously in 16, including six patients with peritonitis. None of the instances occurred as a postoperative infection. Ten of the patients had an associated malignant disease including carcinoma of the colon and rectum in six, hematologic malignant conditions in three and carcinoma of the gallbladder in one. Of the remaining six patients, four had evidence of immune suppression (two had leukopenia, one was preleukemic and one had undergone a postcadaver renal transplant), one had diabetes and one had overwhelming sepsis due to a perforated gallbladder with peritonitis. Only three of the 19 patients were otherwise healthy, and infection occurred after trauma in all of these patients. Four patients were moribund upon admission and died before initial therapy was completed. In the other 15 patients, treatment consisted of administration of penicillins and broad spectrum antibiotics and debridement, as well as hyperbaric oxygen in 13 patients. Thirteen of 19 patients died and eight of ten with malignant disease died. The data show a striking relationship between Clostridium septicum and both malignant disease and immune suppression. PMID- 3344449 TI - The mechanism of the inhibitory action of neurotensin on pentagastrin-stimulated gastric secretion in dogs. AB - Neurotensin is a potent inhibitor of pentagastrin-stimulated gastric acid secretion. This study was done to investigate the possible role of vagal innervation and of prostaglandins on this inhibitory effect. Five dogs with gastric cannulas were infused with pentagastrin (1 microgram per kilogram of body weight each hour) for 210 minutes. In the 60 to 150 minute period, neurotensin (5.5 micrograms per kilogram of body weight each hour) was infused. Neurotensin significantly decreased pentagastrin-stimulated gastric acid output, while the simultaneous administration of indomethacin (bolus of 1 milligram per kilogram of body weight plus infusion of 0.5 milligrams per kilogram each hour) abolished the effect of neurotensin. After truncal vagotomy, the inhibitory effect of neurotensin was again studied. Since the sensitivity of the stomach to pentagastrin decreased after vagotomy, the dose of pentagastrin was doubled (2 micrograms per kilogram of body weight each hour) in order to achieve acid stimulation comparable with the levels before vagotomy. After vagotomy, neurotensin inhibited the effect of pentagastrin in a manner similar to that shown before vagotomy. The inhibitory potency of neurotensin on gastrin stimulated gastric secretion is independent of the vagus, but requires intact synthesis for prostaglandins. PMID- 3344450 TI - Toxicity of polymerized hemoglobin solutions. AB - Four solutions of bovine polymerized hemoglobin (BPHS) and rabbit plasma were used to replace one-third of the blood volume in five groups of rabbits. The first three solutions were "impure" because of the presence of stromal phosphatidyl-ethanolamine and phosphatidyl-serine in BPHS-1, environmental endotoxins in BPHS-2, and a large amount of higher molecular weight hemoglobin glutaraldehyde polymers in BPHS-3. These solutions caused a 33 per cent mortality rate and significant morbidity which was characterized by hemodynamic instability, respiratory and renal insufficiency, elevation of hepatic enzyme levels, thrombocytopenia, leukopenia, disseminated intravascular coagulation (DIC) and activation of the alternate pathway of complement. Histopathologic changes found in the heart, lungs, liver, spleen and kidney were characterized by a combination of ischemic and inflammatory lesions. Fibrin thrombi were visible by immunofluorescence in the microcirculation. In contrast, the fourth solution (BPHS-4) was free of the aforementioned impurities; caused no deaths and minimal morbidity, which was limited to elevated levels of serum glutamic pyruvic transaminase and reduction of creatinine clearance; no DIC or complement activation, and mild histopathologic changes which were exclusively ischemic in nature. The results of this study indicated that the toxicity of polymerized hemoglobin solutions is due principally to the presence of impurities. Pure hemoglobin does exhibit mild toxicity when compared with a control solution which is most likely due to a vasoconstrictor effect of oxyhemoglobin. PMID- 3344451 TI - The relation of thyroid indices in the critically ill patient to prognosis and nutritional factors. AB - Thyroid indices and nutritional assessment values were measured in 73 critically ill euthyroid patients within 48 hours of admission to the medical or surgical intensive care unit. Significantly increased rates of mortality were observed among patients with decreased T3 or T4 levels or elevated T3UR or rT3 values. Alterations in thyroid function tests were associated with changes in certain putative nutritional indices, including serum albumin and transferrin concentrations, triceps skin fold and skin test reactivity. The data indicated that thyroid parameters measured early in the critical phase of illness are predictive of subsequent outcome. The pathogenesis of altered thyroid hormone metabolism is unknown, but nutritional deprivation may be an important contributing factor. PMID- 3344452 TI - Continuous epidural morphine analgesia after radical operations upon the pelvis. AB - Sixty-seven patients with gynecologic malignant disease received continuous epidural morphine as a postoperative analgesic after radical surgical treatment. An average of 0.005 milligrams per kilogram of body weight per hour of morphine was given, with a mean total postoperative dose of 33.42 milligrams. Pain control was excellent in 88 per cent of the patients and no major complications occurred with this technique. Side effects included: nausea (33 per cent); vomiting (9 per cent), and generalized pruritus (25 per cent). Epidural morphine provided a constant pain-free state with unimpaired consciousness, normal motor function and hemodynamic stability. This technique allows the early institution of aggressive physiotherapy with an actively participating patient and provides an ideal postoperative analgesia for the high risk patient to be cared for in an intensive nursing area. PMID- 3344453 TI - Carotid endarterectomy in octogenarians and nonagenarians. AB - Experience with carotid endarterectomy (CE) in patients 80 years of age and older is analyzed by reviewing results in terms of patient survival, quality of life and recurrence of symptoms of cerebral ischemia. During a 12 year period, 90 octogenarians underwent CE. Ages ranged from 80 to 93 years with a mean of 83 years. Two groups of patients younger than 80 years of age were selected from the series for comparison. There were no differences between age groups with respect to operative mortality and morbidity, with two deaths and one stroke in the elderly group. Follow-up periods ranged from one to 120 months with a mean of 39 months. There were two late strokes in patients older than 80 years of age. At late follow-up study, 87 per cent of patients operated upon for hemispheric symptoms were free of neurologic deficits; in contrast, only 67 per cent of those operated upon for nonhemispheric symptoms were symptom-free (p less than 0.05). The incidence of occlusive disease of the intracranial portion of the internal carotid artery was higher in the elderly group (p less than 0.01). The presence of intracranial occlusive disease represented an unfavorable factor in regard to the results of CE in patients with nonhemispheric symptoms. The over-all five year survival rate was 60 per cent. These data indicate that advanced age alone should not be considered a contraindication to CE. Excellent results should be expected in instances of operations performed for hemispheric symptoms. In instances of nonhemispheric symptoms, results are less encouraging because of the high incidence of intracranial carotid occlusive disease. PMID- 3344454 TI - Nonoperative management versus early operation for blunt splenic trauma in adults. AB - Forty-eight adult patients with isolated splenic trauma from blunt injury were analyzed during a six year period (1980 to 1986). Early laparotomy was performed upon 38 patients and splenic preservation was accomplished in 18. The remaining ten patients who were hemodynamically stable were managed nonoperatively with close monitoring. Splenic injuries were confirmed by one of the imaging methods, such as computed tomography, radionuclide scan or ultrasound. One patient with known hepatic cirrhosis underwent embolization of the splenic artery and recovered. Nonoperative treatment failed in seven of the remaining nine patients, mandating an exploratory laparotomy between the third and tenth day of admission. In six of the seven patients, splenic preservation was unsuccessful, necessitating a splenectomy. The length of hospital stay was longer for this latter group (a mean of 15.8 days) than for patients who had splenorrhaphy (a mean of 7.5 days), or splenectomy (a mean of 8.7 days, p less than 0.001). Patients managed nonoperatively required more units of blood compared with those undergoing splenorrhaphy (4.1 units versus 1.7 units, p less than 0.01). A review of the literature reveals that splenic preservation is possible in less than 25 per cent of the patients who fail to respond to nonoperative management. We conclude that splenic injuries after blunt trauma in adults are treated best by early laparotomy in order to achieve maximal splenic preservation. PMID- 3344455 TI - Total pelvic exenteration as a therapeutic option in advanced malignant disease of the pelvis. AB - Between 1966 and 1986, 99 patients underwent total pelvic exenteration at the Ellis Fischel State Cancer Center. Fifty-eight per cent of these were done for recurrence of carcinoma of the cervix uteri after radiation. The second most common type of malignant condition treated with total pelvic exenteration was localized advanced adenocarcinoma of the rectum. Fourteen of 99 patients died prior to discharge and after five years, 36 of 80 patients had survived. Seven deaths after discharge were attributed to the operation. There were 97 complications in 64 of the 99 patients after total pelvic exenteration prior to discharge. Between 1976 and 1981, one out of 14 patients undergoing total pelvic exenteration for locally advanced recurrent carcinoma of the cervix uteri died prior to discharge. Eight of 13 of the patients who survived that operation lived for five years. Total pelvic exenteration should be strongly considered in selected patients with locally advanced malignant lesions of the pelvis. PMID- 3344456 TI - Treatment of displaced fractures of the sternum. AB - An easy technique is presented for the treatment of simple transversal fractures of the sternum when loss of alignment of the fractured extremities occurs. This technique produces instant relief and will avoid open reduction and wiring in most instances of uncomplicated fractures. PMID- 3344457 TI - Operative cholangiography using a modified disposable vascular clip. AB - After frequent use of this modified disposable clip, obtaining cholangiograms has been both easy and quick while minimizing trauma to the tissues of the cystic duct. The clip can be used safely through any incision, small or large, and it is a good tool in facilitating the interoperative cholangiogram. PMID- 3344458 TI - An easy way to convert a loop esophagojejunal anastomosis to Roux-en-Y anastomosis. PMID- 3344459 TI - Mobilization of the spleen in splenic salvage. PMID- 3344460 TI - Technique for needle biopsy to confirm suspected hepatic metastases at laparotomy. PMID- 3344461 TI - Clavicular osteotomy and internal rigid fixation to the super extended pectoralis major musculocutaneous flap. PMID- 3344462 TI - Epidermoid cysts of the fourth ventricle. AB - Epidermoid tumors located in the fourth ventricle are exceedingly rare. Seven cases of this pathological condition were observed during a 10-year period. Patients were mostly middle-aged men, with a clinical history of relatively short duration (5 months). Clinical symptoms consisted of vertigo and ataxia, followed by incoordination, dysmetria, and tremor at a later stage. Computed tomography scanning represented the main diagnostic technique for these lesions, and typically showed a highly hypodense, round-shaped area within the fourth ventricle, occasionally accompanied by hydrocephaly. Subtotal surgical removal of the cysts produced excellent results in 86% of the cases. The implications of these findings are discussed. PMID- 3344463 TI - Examination of autologous and embryonic cortical brain tissue transplantation to adult brain cortex in rats. AB - Autologous and embryonic cortical brain tissue was transplanted to adult rats in order to reconstruct experimentally degenerated cortical brain tissue. Rats were decapitated within 6 or 12 weeks. Viability of the graft tissues was studied by light and electron microscopy. Embryonic cortical brain tissue grafts became enlarged but adult cortical brain tissue grafts were found to be unaltered. Electron-microscopically observed mitochondria and other cell organellae and the newly vascularized areas clearly showed that the graft tissues were alive. PMID- 3344464 TI - Tumors of the brain in the Sudan. AB - One hundred twenty-three cases of tumors of the brain encountered in patients admitted over a 10-year period (1971-1981) at the Neurosurgical Section, Shaab Teaching Hospital, Khartoum, Sudan are presented. Special emphasis is directed at the high incidence (45.5%) of meningiomas. Clinical and pathological findings are reported. PMID- 3344465 TI - Surgical management of acoustic neuromas during the last five years. Part I. AB - A consecutive series of 94 patients with acoustic neuromas, who were treated in the years 1980-1984, was reviewed. Hearing loss was the most common presenting symptom. During 1980-1984, all acoustic neuromas were treated surgically; 93 cases had a total excision and only one case had a subtotal excision. Mortality and morbidity were low and patients who had a fair to poor outcome rating had large tumors. Overall, cranial nerve VII was preserved in 64.1% of cases, while cranial nerves VII and VIII were anatomically preserved in 27% of cases. PMID- 3344466 TI - Surgical management of acoustic neuromas during the last five years. Part II: Results for facial and cochlear nerve function. AB - Postoperative facial and cochlear nerve function in 83 consecutive patients with acoustic neuromas, who were undergoing their initial surgical procedure during 1980-1984, have been examined. The facial nerve was preserved in anatomic continuity in 71% of cases. Various nerve grafting procedures were used when the facial nerve was divided; the most common of these was a faciohypoglossal anastomosis, which was performed in 20 cases. The facial and cochlear nerves were anatomically preserved in 30.1% of all patients having their initial surgical procedure. Good speech discrimination was preserved in four patients, whereas more crude hearing was preserved in six other patients. PMID- 3344467 TI - Tumor-simulating giant serpentine aneurysm of the posterior cerebral artery. AB - A case of a giant aneurysm of the proximal segment of the posterior cerebral artery is reported. Complete neuroradiologic (computed tomography scan, angiography, magnetic resonance imaging) and pathological studies were performed. This type of aneurysm is extremely rare and may be difficult to differentiate from a cerebral tumor, both clinically and on computed tomography scan. Vertebral angiography is usually necessary to make, or confirm, the diagnosis. PMID- 3344468 TI - Subdural effusion in the acute stage of Kawasaki disease (Mucocutaneous lymph node syndrome). AB - A 6-month-old girl with complications of subdural effusions at the acute stage of Kawasaki disease is reported. Based on the pathology of Kawasaki disease and considering the possibility of systemic vasculitis, the subdural effusions were assumed to be attributable to vasculitis involving the dura mater. PMID- 3344469 TI - Combined thyrotroph and lactotroph cell hyperplasia simulating prolactin secreting pituitary adenoma in long-standing primary hypothyroidism. AB - Primary hypothyroidism accompanies more than 50% of clinically significant pituitary thyrotroph adenomas. Hypothyroidism may also produce pituitary enlargement secondary to thyrotroph hyperplasia and present with a sellar mass and hyperprolactinemia. Three hypothyroid patients who presented with presumed prolactin-producing adenomas are reported. Although laboratory and radiologic abnormalities of pituitary enlargement may resolve after corrective thyroid therapy, our patients showed no such response and underwent operation. Histologic examination revealed no adenomas, but thyrotroph and lactotroph hyperplasia were present. Thyrotroph hyperplasia probably results from lack of negative feedback of thyroid hormone upon the anterior pituitary. Whether this is due to hypothalamic release of thyrotropin-releasing hormone (TRH) or another mechanism is unclear. Lactotroph hyperplasia may result from excess TRH, which stimulates lactotrophs with resultant hyperprolactinemia, or from reduced hypothalamic dopamine, thereby facilitating prolactin secretion. This study suggest that (a) hyperprolactinemia in hypothyroidism is not necessarily due to the "stalk section effect" secondary to pituitary enlargement, and (b) patients with primary hypothyroidism and sellar mass should initially be managed medically so that potentially reversible pituitary hyperplasia is not mistaken for adenoma. PMID- 3344470 TI - Obstructive hydrocephalus due to a giant aneurysm of the internal carotid bifurcation. AB - A rare case of obstructive hydrocephalus associated with a giant aneurysm of the internal carotid artery is presented. The giant aneurysm, which was located in the prepontine cistern, was initially thought to be of basilar artery origin. Cerebral computed angiotomography had the most diagnostic value in disclosing the partially thrombosed giant aneurysm and its relationship with the surrounding arteries. After undergoing a ventriculoperitoneal shunt operation, the patient's clinical symptoms markedly improved. PMID- 3344471 TI - Intracerebral hemorrhage from a metastatic brain tumor. Importance of differential diagnosis preceding stereotaxic hematoma aspiration. AB - Three cases of sudden intracerebral hemorrhage, which were diagnosed as hemorrhage from metastatic brain tumors following stereotaxic aspiration of a hematoma, are reported. Two cases had subcortical hemorrhage and one had cerebellar hemorrhage. Neither contrast-enhanced computed tomography scans nor angiograms revealed any findings other than those indicating the hematoma in all three cases. However, retrospective study of the anamnesis showed very mild symptoms due to metastasis to the brain or spinal cord in one case each. In cases of intracerebral hematoma located at atypical sites, extreme care is required for the differential diagnosis. PMID- 3344473 TI - Quality of survival after head injury. PMID- 3344472 TI - Angiolipoma of the spinal cord. Magnetic resonance imaging and microsurgical management. AB - Radiologic diagnosis of intramedullary lipomas has been unreliable for a long time and many of these tumors have not been recognized. The introduction of computed tomography, and lately of magnetic resonance imaging, has led to great progress in the accurate identification of spinal cord tumors as well as in the recognition of type specificity of these lesions. An evaluation of the diagnostic value of magnetic resonance imaging and microsurgical technique for the optimal therapeutic outcome is discussed. PMID- 3344474 TI - Trapped fourth ventricle. PMID- 3344475 TI - An objective perspective on neurosurgical publications. The value of citation analysis. PMID- 3344476 TI - Caring for AIDS patients. PMID- 3344477 TI - A Cs-137 afterloading device. Preliminary results of cell kinetic effects of low dose-rate irradiation in an experimental tumour. AB - A Cs-137 afterloading technique is described which can be used in experimental tumours. Preliminary results, obtained with the human cervical carcinoma ME-180 xenografted to nude athymic mice, demonstrated that 20 Gy of low dose-rate irradiation induced an important redistribution of cells over cell cycle. The proportion of cells in G2-phase increased from 14.4% to 44.2% at 140 hours after irradiation. This method allows an accurate calculation of the dose-rate distribution in the tumour. Investigations of the cell kinetic effects of low dose-rate irradiation, at different dose-rates and different total doses, are therefore facilitated by the technique. PMID- 3344478 TI - Mathematical models of cumulative effect and optimization of fractionation regimes. AB - Different (most known) mathematical models are shortly described and basic assumptions the individual models are based on are discussed and critically examined. Advantages and shortages of individual models are mentioned. A semiphenomenological model is then used to demonstrate some possibilities how to make use of the mathematical models in attempts of optimizing the fractionation approaches in individual cases. PMID- 3344479 TI - [Results of radiotherapy treatment of nasopharyngeal tumors depending upon the pathologico-anatomic diagnosis]. AB - Malignant nasopharyngeal tumors are rare, so that there are only few communications about treatment results in dependence on histological findings. The histological classification of malignant tumors, especially in case of malignant lymphomas, has changed considerably during the last few years. All histological preparations available from 157 patients treated by radiotherapy between 1960 and 1985 have been reassessed. Above all it was attempted to classify the formerly current diagnoses "retothelial sarcoma" and "lymphosarcoma" according to today's criteria and to assign to a histological type those tumors which could not be exactly classified hitherto. This proceeding has increased especially the group of malignant non Hodgkin's lymphomas from seven to 29 patients. The therapy results achieved after irradiation are presented in dependence on histological data and compared to the results communicated in literature. A certain stagnation is found for the last few years showing that an optimum of present therapy possibilities has been reached at the individual therapy centers. PMID- 3344480 TI - [Results of radiotherapy in advanced oropharyngeal carcinomas. Primary and postoperative radiotherapy versus radiotherapy following polychemotherapy]. AB - Within the period from 1971 through 1984, 185 patients with advanced oropharynx carcinomas were irradiated during primary therapy. The influence of a standardized chemotherapy (Heidelberg scheme) as initial therapeutic measure is investigated. Whereas 10% of the patients were treated in this way from 1971 through 1977, this part was 78% from 1978 through 1984. The remission rate after chemotherapy was 62%; the greater part of these remissions were partial remissions. The influence of chemotherapy was seen in increased radical macroscopic tumor resections, but also in an increased frequency of radiotherapy interruptions in case of severe mucous reactions. An increased rate of complete tumor remissions after irradiation was not observed. Nonresponders to chemotherapy showed a significantly poorer response to subsequent radiotherapy. There were no differences in survival times between the two periods in spite of the considerably modified therapy methods. PMID- 3344481 TI - [Field-integrated dosage modification (FIDM). 2. The physical principles of the procedure]. AB - A method is suggested and described which allows to introduce areas of different sizes, shapes, sites, and doses into a photon irradiation field. The bases for calculation and manufacturing of such irregular field stops containing integrated dose modification blocks are, according to precision requirements and data acquisition possibilities, either information provided by computed tomography or conventional planning radiographs. The following standard parameters are required as input data: sizes, shapes, and positions of the partial fields within the total irradiation field, depth of the reference plane, absorption coefficient of the modification material used, proportions of the planned dose modification, radiation quality, and other radiation field parameters. For the calculation of the dose distributions within the generally irregularly shaped irradiation volumes, an iterative algorithm has been formulated following the differential sector addition method and an equivalent TAR scheme. The quality of such a modifier can be checked by standard dosimetric methods. Deviations from the planned dose modification can be defined as sigma = +/- 5% for the radiation qualities employed (60Co gamma radiation and 15 MeV bremsstrahlung of a linear accelerator). PMID- 3344482 TI - [Histological and morphometric research on rhabdomyosarcoma in the rat after irradiation and microwave hyperthermia]. AB - Cellular effects of a combined treatment with X-rays (15 Gy) and local microwave hyperthermia (43 degrees C, 60 min) on the tumor tissue of the rhabdomyosarcoma R1H of the rat were studied with light and electron microscopy. The results were compared with the cell reactions obtained after X-rays (15 Gy) alone. The histological results and the morphometric data show that the time course of cell damage changes individually with the treatment applied. After radiation alone a cell oedema occurs within some days. After a combined treatment, however, a marked cell oedema and cell lysis is already observed after 24 hours. An intensive shrinking of the cell nuclei is found at day 6th, attended with pyknosis, karyolysis and cell fragments in the extended extracellular area. In comparison with radiation alone the processes of repair and repopulation in the R1H tissue are remarkably delayed after a combined treatment. PMID- 3344483 TI - Late results after femoral artery embolectomy. AB - A review of 100 femoral artery embolectomies performed on 88 consecutive patients during a 10-year period was conducted to establish immediate and long-term results. There were 48 (55%) male and 40 (45%) female patients. Ages ranged from 33 to 97 years (mean, 73 years). Local anesthesia was used in 84 (84%) cases. Fifteen (17%) patients died within 30 days of the procedure. Major limb amputation was required within 30 days of operation in 16 (16%) patients. Mortality rate in the group of patients needing early amputation was 50% compared with 11% for those who underwent successful embolectomy procedures (p less than 0.001). Current follow-up was established for all patients. Five-year and 10-year survival rates for the entire group were 40% and 35%, respectively. The most frequent causes of late death after femoral artery embolectomy were arteriosclerotic heart disease (26%), cerebrovascular accident (26%), and advanced carcinoma (21%). All 39 remaining survivors were located 8 to 126 months (mean, 48 months) after discharge to complete a questionnaire designed to assess quality of life and symptoms of vascular insufficiency. Thirty-five (90%) survivors were fully ambulatory and 27 (70%) lived in their own homes. Although early survival is decreased after femoral embolectomy, long-term survivors can be expected to live independently with excellent limb salvage and function. PMID- 3344484 TI - Sequelae of limited amputation. AB - Ninety patients underwent toe amputations because of vascular disease; 21% required higher amputation and 21% healed without further surgery (i.e., revascularization). Of 60 patients who required bypass surgery, 52 underwent successful first amputations and eight required higher amputations. No difference was seen between diabetic and nondiabetic patients in eventual limb salvage; however, men fared better than women. Without bypass surgery, 11 of 30 patients required a higher level of amputation. No patient's toe amputation site healed with an ankle-to-brachial index of less than 0.35. The judicious use of toe amputation remains an important tool in the surgeon's quest for limb salvage. PMID- 3344485 TI - Aortoiliac reconstruction in obese patients. AB - In the patient with limb-threatening ischemia and aortoiliac occlusive disease surgical reconstruction with a prosthetic bypass, because of its safety and durability, has emerged as the treatment of choice. In obese patients, however, such therapy might be eschewed because of the frequent coexistence of multiple risk factors and the large size of these patients. In ten obese patients who had limb-threatening ischemia or rapidly worsening disabling claudication and aortoiliac occlusive disease, direct aortoiliac reconstruction was performed. There were no perioperative deaths, and only one major complication occurred in this group. The cumulative 5-year graft limb-patency and limb-salvage rates were each 90%. Despite the higher risk and unusual technical challenges that obese patients may present, direct reconstruction is the preferred treatment for aortoiliac occlusive disease and limb-threatening ischemia. PMID- 3344486 TI - Epidural bupivacaine and morphine plus systemic indomethacin eliminates pain but not systemic response and convalescence after cholecystectomy. AB - We studied 24 patients undergoing elective cholecystectomy and randomized to either conventional postoperative pain treatment, with intermittent nicomorphine (10 to 15 mg) and acetaminophen (1 gm) on request, or thoracic epidural analgesia with plain bupivacaine for 48 hours and epidural morphine 4 mg every 8 hours for 96 hours plus systemic indomethacin 100 mg every 8 hours for 96 hours. Epidural analgesia for pin prick extended from the fourth thoracic to the first lumbar nerve for 48 hours. Assessments of pain, various injury response parameters, peak flow, and subjective feeling of fatigue were performed preoperatively, 3 and 6 hours after skin incision, and 1, 2, 4, and 8 days postoperatively. The epidural analgesia-systemic indomethacin treatment eliminated postoperative pain during rest and coughing. In contrast, only a minor and clinically unimportant modulation of the conventional perioperative and postoperative changes in plasma cortisol, glucose, transferrin, orosomucoid, leukocyte and differential counts, rectal temperature, peak flow, and fatigue was observed. Our results suggest that factors other than pain per se must be controlled in order to reduce postoperative morbidity. PMID- 3344487 TI - Assessment of resectability of esophageal cancer by computed tomography and magnetic resonance imaging. AB - Sixty patients with esophageal cancer infiltration of mediastinal structures and metastasis to lymph nodes were prospectively evaluated by computed tomography and magnetic resonance imaging and then underwent surgical resection of the tumor (n = 57) or diagnostic thoracotomy (n = 3). Lymph nodes were excised from standardized locations and examined histologically. Sensitivity and specificity of both methods for all criteria were found so low that the value of these methods for planning surgery--or for stratification to different therapeutic arms in comparative studies--must be questioned. PMID- 3344488 TI - Goiter with severe respiratory compromise: evaluation and treatment. AB - Goiter with major respiratory compromise is uncommon but troublesome. Evaluation and treatment of this condition are controversial. Of a total of 2,908 goiters operated on over a 17-year period, 58 cases with this particular complication were studied retrospectively to define optimal management. Twenty-two patients had severe or acute dyspnea, and four of them required immediate tracheal intubation. Thirty-six patients had chronic dyspnea without cyanosis. Carcinoma was present in these two groups in 50% and 11% of patients, respectively. Results of our retrospective study are as follows: long-standing tolerance of goiter did not preclude the possibility of compressive respiratory distress or carcinoma. Optimal management of goiter with respiratory compression was obtained when surgery was delayed until satisfactory operating room conditions and adequate possibilities of interpretation of pathologic conditions were united. In case of respiratory distress, tracheal intubation allowed to abide without risks. In other patients preoperative investigations were kept to a minimum. Technical artifices facilitated the extraction of the goiter via cervicotomy without sternotomy in 92% of patients with minimal morbidity. Whenever necessary, endotracheal intubation obviated the need for tracheostomy. These data suggest preventive removal of all large or substernal goiters. PMID- 3344489 TI - Anatomic resection of liver segments V and VI. AB - We describe a surgical technique that allows identification and severing at the hilum of the hepatic artery and portal vein branches, which perfuse only segments V and VI of the right lobe of the liver. This is a technique that makes possible an anatomic resection of those segments. The bile duct and hepatic vein branches are ligated only when the liver parenchyma is sectioned. The technique was used in three patients with liver tumors. No patient received blood transfusions, and no postoperative local complications were observed. PMID- 3344490 TI - Spontaneous splenic rupture in an adult with mumps: a case report. PMID- 3344491 TI - Coumarin: friend and foe. PMID- 3344492 TI - Major operative trauma increases peripheral amino acid release during the steady state infusion of total parenteral nutrition in man. PMID- 3344493 TI - [Mental health protection (2). Psychiatric nursing--as seen from an existentionalistic viewpoint]. PMID- 3344495 TI - [How does business democracy function?]. PMID- 3344494 TI - [Breast feeding and AIDS]. PMID- 3344496 TI - [Cancer patients at the polyclinic]. PMID- 3344497 TI - [Team work with nursing assistants. Interview by Erik Lie]. PMID- 3344498 TI - [Nurses and smoking]. PMID- 3344499 TI - [Practice and theory must always go hand in hand. Interview by Kjell Arne Bakke]. PMID- 3344500 TI - [Ethical guidelines for nursing research in Scandinavia]. PMID- 3344501 TI - [San Francisco is hard hit by AIDS epidemic]. PMID- 3344502 TI - [Funen's County Board active for nurses native to Odense]. PMID- 3344504 TI - [Knowledge, values and rights as basis for decision making]. PMID- 3344503 TI - [No basis for conversion of jobs]. PMID- 3344505 TI - [SSN (Scandinavian Nurses' Cooperative). Consciousness about decisions and responsibility will grow]. PMID- 3344506 TI - [Health policy. 'Health for All' is a movement and a contest for money and power]. PMID- 3344507 TI - [Poor working environment is biggest work problem for many nurses]. PMID- 3344508 TI - [Why put a decreasing momentum on EDP?]. PMID- 3344509 TI - [Nurses in Thisted will have consumers' influence]. PMID- 3344510 TI - [Health visitors in the community of Vejle have introduced EDP]. PMID- 3344511 TI - [Health visiting in Herning becomes visible with EDP]. PMID- 3344512 TI - [The future called the 'Green System' in Hvidovre Hospital]. PMID- 3344513 TI - [EDP--long time between idea and reality]. PMID- 3344514 TI - [EDP--entire life on a magnetic disk]. PMID- 3344515 TI - [EDP-nurses]. PMID- 3344516 TI - Motorcycle helmet laws--legislative frivolity or common sense. PMID- 3344518 TI - Lessons from postmortem examination for those who care. PMID- 3344517 TI - The Texas Natural Death Act. PMID- 3344519 TI - Lung cancer trends and prospects for prevention: Texas and United States. PMID- 3344521 TI - How good are your collection efforts? PMID- 3344520 TI - Legislation, physicians, AIDS and ethics--a Texas perspective. PMID- 3344522 TI - Oral cadmium chloride intoxication in mice: effects of dose on tissue damage, intestinal absorption and relative organ distribution. AB - The acute toxicity of soluble cadmium salts has almost exclusively been studied experimentally after parenteral exposures, where acute mortality is caused by hepatic necrosis. This report describes an alternative experimental model using oral exposure. A single oral toxic dose of CdCl2 to mice induced toxic gastroenteritis; subsequent hepatic and renal lesions were also observed. Whole body gamma-counting after a single oral toxic 109CdCl2 dose to mice showed a dose dependent delay of the fecal excretion of non-absorbed cadmium. This delay was absent when a low, non-toxic dose was administered. This effect is most likely due to decreased peristalsis and, at higher doses, intestinal atony due to oral cadmium toxicity. After fecal elimination of non-absorbed cadmium, the residual body burden of cadmium expressed as percent of initial dose reflects the fractional intestinal cadmium absorption due to slow reexcretion of absorbed cadmium. The fractional absorption increased with increasing doses of cadmium. The relative cadmium deposition in brain, testes and intestines decreased with increasing dose, whereas the relative liver deposition increased with dose. The delayed fecal elimination and increased fractional absorption of cadmium may significantly contribute to the development of both local and systemic toxicity in oral cadmium intoxication. PMID- 3344523 TI - Prevention of diisopropylphosphorofluoridate (DFP)-induced skeletal muscle fiber lesions in rat. AB - The objective of the present investigation was to assess the comparative efficacy of prophylactic treatment with d-tubocurarine (d-TC) (0.075 mg/kg), atropine sulfate (16 mg/kg), and atropine methylnitrate (16 mg/kg), employed singly or in combination against the diisopropylphosphorofluoridate (DFP)-induced myopathy in rat. DFP (1.5 mg/kg, s.c.) produced signs of cholinergic toxicity with predominantly peripheral involvement manifest as severe muscle fasciculations beginning within 5-7 min and persisting in excess of 4-6 h. Maximal muscle fiber necrosis was observed within 24 h. Rats were protected against the apparent behavioural and morphological changes as well as electrophysiological signs of neuromuscular toxicity by all pretreatment agents. Combined pretreatment with d TC (0.075 mg/kg, s.c.) and atropine methylnitrate (16 mg/kg, s.c.) was found to be most effective in attenuating DFP-induced muscle fiber necrosis as evidenced by complete absence of lesions and the prevention of DFP-induced hyperactivity in nerve and muscle. Significant protection was afforded by all pretreatment agents when given alone. It is suggested that the pretreatment agents act presynaptically by preventing drug-induced backfiring and muscle fasciculations possibly by reducing the release of acetylcholine (ACh). The protective drugs in the concentrations used had no significant effect on the normal characteristics of conduction and transmission. PMID- 3344524 TI - Depletion of liver regulatory heme in benzene exposed rats. AB - The effect of a single dose of benzene (0.5 ml/kg body wt i.p.) on the heme saturation of tryptophan pyrrolase activity in liver was examined. There was a significant decrease in the heme saturation of hepatic tryptophan pyrrolase, suggesting depletion of "regulatory heme". After benzene administration there was significant increase in delta-aminolevulinate (ALA) synthetase activity (approx. 2-fold) while delta-aminolevulinate dehydratase activity was significantly decreased, however, ferrochelatase and heme oxygenase activities were unaltered. Administration of tryptophan to benzene pretreated rats showed a reversal of benzene effects on heme synthesizing enzymes: there is an increase in the heme saturation of tryptophan pyrrolase and decrease in delta-aminolevulinate synthetase. However, there was no significant alteration in the activity of delta aminolevulinate dehydratase. PMID- 3344525 TI - Transplacental passage of titanium after treatment with titanocene dichloride. AB - The passage of titanium-containing metabolites across the placenta into the embryonal compartment was investigated by analyzing the titanium (Ti) content in embryos/fetuses at various intervals between 1 h and 24 h after treatment of pregnant mice with single doses of the antitumor agent titanocene dichloride (C5H5)2TiCl2 (60 mg/kg) on days 10, 12, 14 or 16 of gestation. The Ti concentration was determined using flameless atomic absorption spectroscopy. After treatment on days 10, 12 or 14, the Ti concentrations were not elevated in comparison to untreated embryos. Only on day 16, i.e. beyond the end of organogenesis, small amounts of Ti were detectable in the fetal compartment 4-24 h after substance application, exceeding the control values by factors ranging between 2 and 3. These results explain the absence of histologic lesions in developing embryonal organs and the lack of multiple teratogenic effects in new borns after application of therapeutic doses of (C5H5)2TiCl2 to pregnant mice during the embryonal organogenesis. PMID- 3344526 TI - Cadmium toxicity on mouse pre-implantation zygotes in vitro: interactions of cadmium with manganese, zinc and calcium ions. AB - Simultaneous treatment with cadmium chloride (5 micrograms/ml medium) and manganese chloride (5 or 10 micrograms/ml medium) was less toxic to mouse pre implantation zygotes in vitro than cadmium alone. Such a protective effect of manganese, resembling that of zinc, suggests that amelioration of cadmium-treated pre-embryos in vitro is not unique to zinc. The amelioration may require only the presence of another divalent metallic ion, such as zinc or manganese, which is capable of competing with cadmium for binding sites possibly involved in uptake. Under calcium-free conditions cadmium embryotoxicity is enhanced, showing a summation effect of the cadmium toxicity and the lack of calcium. This supports the notion that excessive exogenous calcium may render the effects of cadmium on compaction inconspicuous. The non-compacted pre-embryos treated with 5 micrograms/ml cadmium in a calcium-free medium had fewer blastomeres than those treated at a lower dose of 1 microgram/ml. Cadmium appeared to inhibit the cleavage from 8-cell to 16-cell stage, but not from 4-cell to 8-cell. PMID- 3344527 TI - On the time-dependence of amphiphile-induced haemolysis. AB - The time-course of haemolysis induced by alkyltrimethylammonium bromides, alkyl sulphates, octaethyleneglycol alkyl ethers, and ZWITTERGENT detergents (C10-C16) was studied. A considerable lag in the development of haemolysis was observed for the C10 and C12 derivatives. The lag exceeded 30 min at low or moderate concentrations of the surfactants. Most of the C14 and C16 derivatives showed no lag but the time-course of the haemolytic reaction of these derivatives indicated biphasic kinetics of haemolysis. With those surfactants showing a lag the critical micelle concentration (cmc) of the surfactants was above the concentrations used in the experiments, whereas cmc in the case of those surfactants showing no lag was close to or slightly below. It is concluded that the differences in the time-course of the haemolytic reaction shown by different derivatives are not connected with the occurrence of micelles in the bulk solution, but that the differences in time-course of the haemolytic reaction reflect differences in the rate of those changes in the membrane molecular organization which precede haemolysis. PMID- 3344528 TI - Evidence for an enterohepatic circulation of ochratoxin A in mice. AB - The distribution and elimination of [3H]ochratoxin A (OTA) from stomach content and tissue, intestine content and tissue, liver, bile, serum and urine of Swiss male mice which had received a single low dose of OTA by intubation was followed as a function of time. The profiles of radioactivity do not show a smooth decline after the absorption period, but an oscillating pattern with rapid declines followed by increases which favour the assumption of an enterohepatic circulation. Between 28% and 68% of conjugated OTA together with OTA cleavage products were found in bile giving evidence for biliary excretion of OTA and its metabolites in mice. When given i.m. to mice [3H]OTA is already found after 30 min in bile and intestine contents and its elimination patterns show several peaks confirming the biliary excretion and the enterohepatic circulation. Cholestyramine, which is known to prevent the enterohepatic circulation of drugs and toxins, changes the profile of elimination of OTA which no longer presents the cyclic pattern. This result is also in favour of an enterohepatic circulation of OTA. When phenylalanine is given together with OTA by oral gavage the toxicokinetics of the mycotoxin change completely in the different body fluids, in stomach and intestine content and tissues. Phenylalanine seems to facilitate the gastric absorption of OTA and the gastro-intestinal transit. It increases also its early excretion into urine and bile. However, its elimination pattern no longer shows the oscillating pattern. Thus phenylalanine seems to inhibit the intestinal reabsorption of OTA conjugates. PMID- 3344529 TI - Cognition and cerebral blood flow fluctuate together in multi-infarct dementia. AB - Longitudinal measurements of cognitive ability measured by serial testing using the Cognitive Capacity Screening Examination (CCSE) were correlated with cerebral blood flow (CBF) throughout (mean +/- SD) 19.9 +/- 12.6 months among 57 patients with multi-infarct dementia, 17 with dementia of the Alzheimer's type, 10 with both, and among 32 age-matched elderly normal controls. Longitudinal CCSE and CBF measurements among controls yielded stable normative values. Reduced mean CCSE scores correlated directly with CBF reductions in patients with multi-infarct dementia (p less than 0.0005) and dementia of the Alzheimer's type (p less than 0.028). Patients with multi-infarct dementia had CCSE scores with retest variability exceeding those of controls (p less than 0.001) and of patients with dementia of the Alzheimer's type (p less than 0.003). CCSE scores and CBF changed together 78.6% (p less than 0.001) of the time in patients with multi-infarct dementia compared with 66.2% of the time (p less than 0.01) in those with both, 62.9% of the time (p less than 0.05) in those with dementia of the Alzheimer's type, and 47.7% of the time (NS) in controls. Further analyses indicated that changes in CCSE scores and CBF were predominantly progressive declines in patients with dementia of the Alzheimer's type, whereas the changes were more bidirectional (both increases and decreases) in patients with multi-infarct dementia; these differences were also significant. Results support the diagnostic usefulness of the Hachinski ischemic scale and confirm that both cognition and CBF fluctuate together among patients with multi-infarct dementia, whereas patients with dementia of the Alzheimer's type exhibit a more stable course, with progressive declines in cognition and CBF. PMID- 3344530 TI - Aneurysmal subarachnoid hemorrhage in Izumo City and Shimane Prefecture of Japan. Incidence. AB - During the 5-year period from 1980 to 1984, the incidence of subarachnoid hemorrhage due only to rupture of aneurysms was investigated in Izumo City, a small city with a population of 79,026. Additionally, to ascertain the relation of incidence to the size of the geographic area and/or population, a similar analysis was made on a larger area of Shimane Prefecture, including Izumo City, with a total population of 789,712. During this 5-year period, a total of 83 patients with aneurysmal subarachnoid hemorrhage were hospitalized in Izumo City, 548 patients in Shimane Prefecture. Ruptured aneurysms were confirmed in 77 cases (93%) in Izumo City and 466 cases (85%) in Shimane Prefecture. The crude annual incidences of aneurysmal subarachnoid hemorrhage for Izumo City and Shimane Prefecture were 21.0 and 13.9 per 100,000 population for all ages, and the age adjusted annual incidences (adjusted to the 1980 population of Japan) were 18.3 and 11.0 per 100,000 for all ages, respectively. For both Izumo City and Shimane Prefecture, the age-specific annual incidences peaked at the ages of 50-69 years, and the highest incidence was 92.3 per 100,000 men from Izumo City in the eighth decade of life. The annual incidence of subarachnoid hemorrhage for Izumo City is the highest reported to date. If a wider area, such as Shimane Prefecture, were studied many patients in poor condition, particularly elderly patients, would be missed. To determine accurately the incidence of aneurysmal subarachnoid hemorrhage, it thus might be better to conduct the study in a small city such as Izumo City. PMID- 3344531 TI - Aneurysmal subarachnoid hemorrhage in Izumo City and Shimane Prefecture of Japan. Outcome. AB - The overall outcome of patients with aneurysmal subarachnoid hemorrhage was investigated in Izumo City and Shimane Prefecture. Of the patients from Izumo City, the clinical grade on admission was Grade I or II in 41% and Grade IV or V in 31%. Of those from Shimane Prefecture, 49% were graded as Grade I or II and 24% as Grade IV or V. The overall mortality rates 1 year after subarachnoid hemorrhage were 46% for Izumo City and 35% for Shimane Prefecture, while the surgical mortality rates were 18 and 15%, respectively. The mortality rates were particularly high among the elderly over the age of 70 years and among unoperated cases. The leading cause of death in these cases was the effect of aneurysm rupture itself, followed by rebleeding and vasospasm. The 5-year survival probabilities according to life table analysis were 50% for Izumo City and 59% for Shimane Prefecture, and a significant difference was observed in survival curves between Izumo City and Shimane Prefecture. It is concluded that the smaller the community studied, the less favorable the overall outcome, mainly because of poorer clinical conditions on admission. PMID- 3344532 TI - Declining mortality from stroke in Allegheny County, Pennsylvania. Trends in case fatality and severity of disease, 1971-1980. AB - Mortality rates for stroke in 1971, 1974, 1977, and 1980 were obtained for residents of Allegheny County in western Pennsylvania. Hospital case fatality ratios were also obtained in the same 4 years for those discharged with the diagnosis of stroke (ICD 430-438 of the Eighth and Ninth Revisions of the International Classification of Disease) in two large hospitals (greater than 400 beds). Age-adjusted mortality rates per 100,000 population have declined significantly in this period for the whole county as well as for the four sex race groups. Case fatality ratio in the two hospitals of the study has decreased from 19.6 to 11%. A change in the severity of the disease manifested by a reduction in the number of comatose patients has occurred, and this reduction in comatose patients was responsible for greater than 80% of the decline in case fatality ratio. Coma appears to be the best predictor of mortality among hospitalized stroke cases (r = 0.6, p less than 0.00001). The recent introduction of computed tomography for the diagnosis of stroke in the late 1970s was accompanied by a twofold increase in the survivorship of stroke patients. However, this increase in survivorship may reflect selection bias and is based on ecological association. Further studies are needed to examine the role of computed tomography in improving survival. PMID- 3344534 TI - Changing prognosis of primary intracerebral hemorrhage: results of a clinical and computed tomographic follow-up study of 104 patients. AB - One hundred four consecutive cases of primary intracerebral hemorrhage hospitalized at the time of stroke were followed until death or for 1 year. All were treated nonsurgically. The 30-day mortality rate was 30%. Good clinical outcome and complete resolution of the lesion on computed tomography were observed in 49 and 13% of patients, respectively. Age, state of consciousness, and size of the hemorrhage on computed tomography scan were reliable prognostic indicators. The long-term survival rate, 66%, was higher than that previously reported and should be considered in future trials evaluating medical and surgical treatment of intracerebral hemorrhage. PMID- 3344533 TI - Admission glucose level in relation to mortality and morbidity outcome in 252 stroke patients. AB - In a prospective study to correlate admission glucose level with neurologic outcome in stroke, 252 acute stroke patients without prior disability and admitted within 24 hours of onset of ictus were assessed. The stroke was classified into one of three types--cortical infarct, lacunar infarct, or intracerebral hemorrhage--by clinical, computed tomographic, and necropsy findings. Fifty-one diabetic patients were excluded from the entire cohort to form a nondiabetic category for analysis. We found that admission glucose level showed a significantly higher degree of correlation with mortality and morbidity (measured as arm function, leg function, and activities of daily living) when cortical (n = 118) and lacunar (n = 58) infarcts were pooled compared with when they were assessed separately. For intracerebral hemorrhage (n = 76), admission glucose level correlated with mortality but not morbidity. This trend persisted despite exclusion of diabetic patients. These results are consistent with previous observations of a correlation between a high admission glucose level and the severity of stroke. The importance of segregating cortical from lacunar infarcts, two groups with a different natural history and prognosis, in any future analysis is emphasized. PMID- 3344535 TI - Amaurosis fugax in a Danish community: a prospective study. AB - A prospective study of amaurosis fugax was carried out in a Danish community (population 481,000); case ascertainment was based on the collaboration of practicing ophthalmologists and general practitioners. Over a 3-year period we registered 131 cases; the annual incidence of "first amaurosis fugax episodes coming to medical attention" was 8.6 and 6.2 per 100,000 population for men and women, respectively. On the basis of a comparison of the age-incidence curves for cerebral and retinal ischemic attacks, the "true" incidence of amaurosis fugax is estimated to be approximately 14/100,000/yr, or 25-30% of the reported incidence of transient ischemic attacks. Clinical and/or radiologic signs of a carotid lesion on the appropriate side were present in 56% of the patients, and an additional 27% had symptoms or signs of other organic cardiovascular disorders. Forty-three (68%) of the 63 patients who underwent arteriography had an atheromatous lesion apparently amenable to carotid endarterectomy. In spite of the case-finding procedures employed in the study, cases of amaurosis fugax suitable for carotid surgery were thus ascertained at a rate of only 3/100,000/yr. This suggests that surgical treatment of patients with retinal ischemic attacks is of minor importance as a preventive measure against stroke in the community. PMID- 3344537 TI - Autopsy study of incidence and distribution of cerebral amyloid angiopathy in Hisayama, Japan. AB - The incidence of cerebral amyloid angiopathy in a general population was evaluated in brains of 400 consecutive autopsies of residents of Hisayama, Japan (November 1971-October 1983). Six samples taken from frontal lobe, parietal lobe, temporal lobe, occipital lobe, hippocampus, and basal ganglia of the same side of each brain were stained with both hematoxylin and eosin and Congo red. The specimens were surveyed microscopically with polarized light for deposition of amyloid in the vascular wall. In 26 cases with brain hemorrhage, the region surrounding the hemorrhagic sites was further examined to study the probable causal relation between cerebral amyloid angiopathy and brain hemorrhage. Cerebral amyloid angiopathy was found in 40 of 218 men (18.3%) and 51 of 182 women (28.0%). The incidence increased with age in both sexes. The frontal lobe was most frequently affected (66 cases), followed by parietal lobe (65), occipital lobe (49), temporal lobe (44), and hippocampus (32); the putamen was never affected. The incidence of cerebral amyloid angiopathy did not correlate with blood pressure or with the severity of cerebral atherosclerosis. Among the 26 cases in which there was brain hemorrhage, only one cerebellar hemorrhage, in an 85-year-old man, was attributed to cerebral amyloid angiopathy. This case showed four microaneurysms in vessels, with cerebral amyloid angiopathy surrounding the hemorrhagic site. Thirty similar lesions were observed in eight cases without brain hemorrhage. Cerebral amyloid angiopathy may play an etiologic role in the development of brain hemorrhage through formation of angionecrosis and microaneurysm. PMID- 3344536 TI - Ischemic infarction in 25 children with tuberculous meningitis. AB - Twenty-five cases (38%) of ischemic infarction occurred among 65 cases of tuberculous meningitis in patients less than 14 years of age. The male:female ratio was 1.3:1. The most frequent clinical findings were meningeal signs, fever, alteration of consciousness, cranial nerve involvement, seizures, and focal neurologic deficit. Twenty-three patients had anterior circulation infarcts, and two more had infarcts in the vertebrobasilar territories. Distribution of infarcts in the anterior circulation was shown by computed tomography in the territories of the following arteries: lenticulostriate, 10 cases unilateral and 6 bilateral; middle cerebral, 3 cases; internal carotid, 1 case; multiple areas, 3 cases. Of the 25 ischemic infarction cases, 23 (92%) had hydrocephalus, 19 (76%) basal exudates, and 2 (8%) tuberculomas. Outcome was poor since no patient with infarction recovered completely. Six died and bilateral subcortical infarcts led to a considerably higher mortality than unilateral ones, whether cortical or subcortical. PMID- 3344538 TI - Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia. AB - The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [14C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2-14C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis. PMID- 3344539 TI - Stable xenon enhanced computed tomography in the study of clinical and pathologic correlates of focal ischemia in baboons. AB - When the lateral striate arteries of baboons are occluded, an immediate cessation of blood flow followed by a transient, minimal restitution of flow occurs in that vascular distribution. These findings are evident from serial xenon/computed tomography cerebral blood flow imaging. In our study, infarction consistently accompanied arterial occlusion for 6 hours or more. The xenon/computed tomography method provides a sensitive, noninvasive technique for examining sequential alterations of cerebral blood flow in small regions deep within the brain. This methodology for recording cerebral blood flow permits correlative studies of cerebral infarction, clinically and experimentally, and allows reasonable inferences about the probabilities of neural tissue damage. PMID- 3344541 TI - Regional cerebral blood flow during hypoxia-ischemia in immature rats. AB - Immature rats subjected to a combination of unilateral common carotid artery ligation and hypoxia sustain brain damage confined largely to the ipsilateral cerebral hemisphere. To ascertain the extent and distribution of ischemic alterations in the brains of these small animals, we modified the Sakurada technique to measure regional cerebral blood flow using carbon-14 autoradiography. Seven-day-old rats underwent right common carotid artery ligation following which they were rendered hypoxic with 8% O2 at 37 degrees C. Before and during hypoxia, the rat pups received an injection of iodo[14C]antipyrine for determination of regional cerebral blood flow. Blood flows to individual structures of the ipsilateral cerebral hemisphere were not influenced by arterial occlusion alone; flows to the contralateral hemisphere and to the brainstem and cerebellum actually increased by 25-50%. Hypoxia-ischemia was associated with decreases in regional cerebral blood flow of the ipsilateral hemisphere such that by 2 hours, flows to subcortical white matter, neocortex, striatum, and thalamus were 15, 17, 34, and 41% of control, respectively. The hierarchy of the blood flow reductions correlated closely with the distribution and extent of ischemic neuronal necrosis. However, unlike the pathologic pattern of this model, the degree of ischemia appeared homogeneous within each brain region. Blood flows to contralateral cerebral hemispheric structures were relatively unchanged from prehypoxic values, whereas flows to the brainstem and cerebellum nearly doubled and tripled, respectively. Thus, ischemia is the predominant factor that determines the topography of tissue injury to major regions of immature rat brain, whereas metabolic factors (intrinsic vulnerability) may influence the heterogeneous pattern of damage seen within individual structures. PMID- 3344540 TI - Regulation of cerebral blood flow after asphyxia in neonatal lambs. AB - In a postasphyxia neonatal lamb model, the responses of the cerebral circulation to hypoxic hypoxia and changes in systemic arterial blood pressure were examined. Ventilated newborn lambs (n = 14) were subjected to a gradual asphyxial insult, resuscitated, and returned to control ventilator settings. During the time 2-5 hours after asphyxia, the responses of cerebral blood flow (CBF), cerebral oxygen delivery (OD), cerebral oxygen consumption (CMRO2), and cerebral fractional oxygen extraction (E) to changes in either arterial oxygen content (CaO2) or mean arterial blood pressure (MAP) were assessed. These data were compared with measurements from nonasphyxiated lambs (n = 7). With hypoxia (n = 7), cerebral blood flow increased (CBF = 646/CaO2 + 44) compared with nonasphyxiated lambs (CBF = 1121/CaO2 + 11). In asphyxiated lambs, cerebral oxygen delivery decreased (OD = 0.41 CaO2 + 6.87), but cerebral oxygen consumption remained stable due to a proportional increase in cerebral fractional oxygen extraction (E = -0.014 CaO2 + 0.65). In nonasphyxiated lambs, cerebral oxygen delivery, consumption, and fractional extraction were unchanged with hypoxia. In response to alterations in blood pressure, both cerebral blood flow (CBF = 0.84 MAP + 6.62) and oxygen delivery (OD = 0.13 MAP + 0.77) were pressure-passive. With hypotension, cerebral fractional oxygen extraction increased (E = -0.003 MAP + 0.69) but not enough to prevent a decrease in cerebral oxygen consumption (CMRO2 = 0.042 MAP + 1.79). In nonasphyxiated lambs, cerebral blood flow, oxygen delivery, consumption, and fractional extraction did not vary with blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344543 TI - Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals. AB - The incidence, average number, and localization of lesions of the white matter detected by the T2-weighted nuclear magnetic resonance images among volunteers without cerebrovascular symptoms have been correlated with the number of risk factors for stroke. Accepted risk factors were arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia, and cardiac disease. The 42 subjects examined were divided into Group A (0-1 risk factor, mean age 59.36 +/- 5.73 years), Group B (2 risk factors, mean age 61.54 +/- 8.33 years), and Group C (greater than or equal to 3 risk factors, mean age 62.57 +/- 9.83 years). Multiple risk factors among the age-matched groups was accompanied by a highly significant increase (p less than 0.001, Group A versus Group B; p less than 0.01, Group A versus Group C) of the incidence of white matter lesions. The average number of white matter lesions was increased (p less than 0.001) when Group A was compared with Groups B and C. Ninety-two percent of the white matter lesions were localized in watershed zones. Only 11 of the 155 abnormalities of the white matter detected by nuclear magnetic resonance imaging could be detected by computed tomography. White matter lesions in T2-weighted images appear to be an early stage of cerebrovascular disease. PMID- 3344542 TI - Segmental duplication of the basilar artery with thrombosis. AB - Duplication or fenestration of the basilar artery, a result of an embryologic malformation, has an incidence of up to 5.3% in the general population. The most common complication of this anomaly is the formation of aneurysms. Thrombosis of a partially duplicated basilar artery developed in a 43-year-old man who complained of visual disturbances followed by seizures and coma, and who eventually died. Autopsy showed a partially organized thrombus occluding both halves of a duplicated portion of the basilar artery, old infarcts in the calcarine cortices, and a recent large infarct in the basis pontis. There was only minimal atherosclerosis of other intracranial arteries, including the vertebral arteries. Hemodynamic disturbances and turbulent blood flow at the site of fenestration may be the cause of the thrombosis that occurred in this artery. PMID- 3344545 TI - Organ procurement in the community hospital. PMID- 3344544 TI - The pharyngeal lymphoid tissue of lampreys. A morpho-functional equivalent of the vertebrate thymus? AB - PE, pharyngeal epithelium; S, blood sinus; T, connective tissue trabecula; End, endothelial cell; Er, erythrocyte; L, lymphocyte; Lb, lymphoblast; Lm, lymphoblast in mitosis; Ma, macrophage; Ret, reticular cell; col, collagen fibres; db, dense body; g, Golgi apparatus; gr, granules; n, nucleus; nu, nucleolus; m, mitochondria; rer, rough endoplasmic reticulum. PMID- 3344546 TI - Expectations for success and perceptions of ability. PMID- 3344547 TI - Recommendations regarding issues facing organ transplantation. PMID- 3344548 TI - Twelve-hour and twenty four-hour preservation of small bowel allografts by simple hypothermia. Survival utilizing cyclosporine. AB - Canine small bowel was harvested and stored by simple hypothermic technique. After 12- and 24-hr storage, respectively, the small bowel graft was allotransplanted into recipients. All animals receiving 12-hr stored grafts (n = 9) survived beyond 5 days. In the 24-hr storage group, 67% of the animals (n = 9) survived beyond 5 days. Successful storage for such extended periods by simple hypothermia has not been achieved previously. Donor pretreatment with antibiotics as well as extensive intraluminal irrigation of the harvested small bowel are considered to be important technical features in this successful preservation. PMID- 3344550 TI - Substitution of 125I-labeled cyclosporine in the radioimmunoassay of plasma cyclosporine. PMID- 3344549 TI - Protection against cyclosporine-induced impairment of renal microcirculation by verapamil in mice. AB - Fluorescence microscopy was used to examine the effect of cyclosporine (CsA) infusion on renal subcapsular (cortical) blood flow in 53 living mice, using FITC dextran (MW: 156,000) as a fluorescent marker. CsA (8-19 mg/kg body weight) given i.v. for 1 min induced complete inhibition of blood flow. A complete standstill of flow was also obtained during a continuous infusion with a rate of 0.8-2 mg/kg/min. With lower infusion rates (0.15-0.23 mg/kg/min), blood flow was partially impaired. In all experiments, the decrease in flow occurred after a 15 25 min delay, suggesting a CsA metabolite or exhaustion of a protective mechanism as the causative agent. Pretreatment with an alpha-blocking agent, phentolamine (1.0 mg/kg), did not prevent the CsA-induced inhibition of blood flow. In contrast, pretreatment with a calcium antagonist, verapamil (0.3-0.4 mg/kg), prevented the impairment of blood flow at low (0.15-0.23 mg/kg/min), and partially at higher (0.8-2.4 mg/kg/min) rates of CsA infusion. Clinical studies are warranted to explore the role of calcium antagonists in the prevention of posttransplant acute cyclosporine-induced nephrotoxicity. PMID- 3344551 TI - Proceedings of the Fifth Scientific Congress of the Transplantation Society of Australia and New Zealand. April 1-3, 1987, Adelaide, South Australia. PMID- 3344553 TI - Impotence. PMID- 3344552 TI - A method for monitoring the collapse of plastic sections as a function of electron dose. AB - We present a method for monitoring the collapse of plastic sections when irradiated in the electron microscope. The two surfaces of the section are separately coated with colloidal gold particles. The section is then tilted to an angle of 45 degrees in the microscope and a series of micrographs recorded, corresponding to increasing total electron dose. The collapse of the specimen normal to the plane of the section causes a relative movement in the image of the two sets of particles marking the two surfaces. By measuring the positions of a few gold particles on each side of the section in each exposure of the series, the collapse and also the in-plane shrinkage can be computed. The sections exhibit a rapid initial collapse, followed by a much slower phase of thinning. These effects should be taken into account when producing quantitative three dimensional maps from tilt series of sectioned material. PMID- 3344554 TI - Penile prostheses. AB - Over the past few years, three new devices have been made available to implant surgeons. These devices are all paired intracorporeal implants that attempt to combine the esthetic qualities of the multicomponent inflatable device with the ease of surgical implantation of the malleable device. Indications as well as technical considerations of penile implant surgery are discussed. PMID- 3344555 TI - Venous surgery for impotence. AB - Venous surgery for impotence is in a dynamic state. The drainage of the corpora cavernosa normally occurs through the crural veins or the cavernous veins and the deep dorsal penile vein. Patients with drainage seen on cavernosography only into a superficial system that persists after injection of intracavernous vasoactive agents are likely to have good results if this drainage is eliminated. This type of patient is not common. A surgical approach that attempts to eliminate the deep dorsal penile system or the crural veins is not as successful. Perhaps subtle arterial disease, concurrent presence of neurologic disease, and collateralization all add to the significant failure rate. Many failures of spontaneous erection will, however, respond to intracavernous injection of vasoactive agents postoperatively. Deep dorsal vein arterialization probably should be reserved for those patients who have an arterial component to their impotence as well as a venogenic cause. PMID- 3344556 TI - Suction device therapy in the management of erectile impotence. AB - The ErecAid System is based on the simple concept of entrapment of blood in the penis following vacuum-assisted penile engorgement by proximally placed elastic constriction bands. The SYNERGIST Erection System is a semirigid external appliance shaped like a condom that is left on the penis after vacuum tumescence has been achieved. Both devices can be used safely by any man who feels that he has an impotence problem, and the outcome is fairly predictable. These devices seem to be especially effective in men with partial impotence, and they offer the impotent man an alternative to surgical placement of penile prosthesis, a surgical revascularization procedure, intracavernosal injection of vasoactive drugs, or sexual abstinence. These devices appear to be safe and relatively inexpensive ways for the impotent man to make his penis rigid enough to engage in sexual intercourse. An impotent man who selects suction-device therapy may still be able to use other forms of treatment should he need or choose it. PMID- 3344557 TI - Ureterocalicostomy. AB - Reconstructive urologic surgery in the upper tract in general is a successful and rewarding procedure. In some settings, however, either complications ensue, or unusual renal anatomy precludes normal procedures. Ureterocalicostomy is an excellent procedure to have available when usual procedures may not be used. In the properly selected patient and with observance of technical details, excellent results may be seen in either primary reconstructive efforts or secondary operations for renal salvage. PMID- 3344558 TI - Neurologic evaluation of erectile dysfunction. AB - Most patients with neurogenic impotence present with a pre-existing neurologic disease. The neurologic assessment in these patients is generally performed to confirm that the underlying neuropathology plays a role in the erectile dysfunction. There are patients, however, with no obvious pre-existing neuropathology who are identified as having a vibratory impairment of the dorsal nerve on penile biothesiometry. Subsequent neurophysiologic testing in several of these patients has confirmed unsuspected neuropathology. An objective evaluation of autonomic cavernosal neurointegrity is still awaited. Such a test may enable the detection of efferent denervation resulting in neurogenic erectile dysfunction that is not clinically obvious. PMID- 3344559 TI - Nocturnal penile tumescence. AB - NPT monitoring remains the best single non-invasive examination to differentiate organic from psychogenic impotence. The need to measure rigidity concurrently with tumescence during NPT is well known, thus making monitoring with the RigiScan, which measures these parameters, the procedure of choice when evaluating NPT. PMID- 3344560 TI - Local microwave hyperthermia in treatment of advanced prostatic adenocarcinoma. AB - Fifteen patients with advanced (T3-4, Nx-2, M0-1) prostatic adenocarcinoma were treated with local microwave hyperthermia (LMwH) applied as the sole method of therapy (automatically controlled set generating 2,450 MHz microwaves with intrarectal applicator). All patients were monitored with a battery of tests, including USG image and volumetry of prostate, bone scintigraphy, serum alkaline phosphatase and serum level of PAP. LMwH sessions were well tolerated and did not cause pain except a moderate sensation of heating in the pelvic region. 8 of these 15 patients responded to the therapy (3x complete remission and 5x partial remission). Involution of the prostatic tumor in responders was accompanied by improvement of the general clinical and urological state. In two responders bone metastases, documented scintigraphically before therapy, disappeared. 7 patients did not respond to LMwH, mostly patients with very large primary tumors. PMID- 3344561 TI - Role of the implantation site on metastatic ability of the murine MBT-2 transitional cell carcinoma. AB - The influence of implantation site on the metastatic behavior of a murine transitional cell carcinoma line (MBT-2) was examined. MBT-2 cells were injected into one of four anatomic sites; subcutaneously, intramuscularly, intravenously or into the footpad, to evaluate the influence of implantation site on the formation and number of metastases. The MBT-2 cell line produced a low incidence of lung metastases after intravenous injection with a mean of 1.1 lung tumors per mouse. Injection of MBT-2 cells into the footpad or subcutaneously did not produce metastases from the primary tumor. Intramuscular implantation, however, resulted in a sixty percent incidence of metastasis with a mean of 8.2 lung nodules per mouse. This study demonstrated a definite implantation site influence on the metastatic ability of the MBT-2 line. PMID- 3344562 TI - Characterization of a newly established human urinary bladder cancer cell line (BT-1). AB - A new human transitonal cell carcinoma cell line has been established in long term tissue culture. The BT-1 cells were derived from a poorly differentiated human bladder cancer. The tumor cell line produces tumors in nude mice. BT-1 has been characterized by cytogenetic and flow cytometric analysis and by isoenzyme typing. As in direct preparations of human bladder tumors, an isochromosome 5p is a consistent marker of the newly established line. The BT-1 cells produce transforming growth factors but do not respond to exogeneous EGF. PMID- 3344563 TI - Patch grafting the renal pelvis and ureteropelvic junction. A comparative study in pigs using lyophilized dura mater and free peritoneum. AB - Lyophilized dura mater (Lyodura) and autogenous free peritoneum were compared in the replacement of the partially resected renal pelvis and uretero-pelvic junction (UPJ) in the pig. The Lyodura and peritoneum grafts were both progressively resorbed, and replaced by fibroblasts which formed a mature scar lined by transitional epithelium, but without smooth muscle regeneration. Lyodura was found to be superior to free peritoneum with a longer time before resorption of the graft, less intense inflammatory reaction, absence of metaplastic bone formation, less risk of urine leak and greater ease of surgical manipulation. PMID- 3344565 TI - Evaluation of surgical staples for ligation of the renal pedicle during nephrectomy. AB - A mechanical stapling instrument was evaluated for ligation of the renal pedicle during nephrectomy in nine healthy sheep. Two forms of disposable loading unit, from which stainless steel surgical staples could be dispensed in double or triple staggered row configuration, were assessed for their proper function when applied across the renal pedicle singularly or in series. The response of the sheep to surgery was assessed by physical, hematological, and serum chemistry evaluations. Tissue healing was determined by gross and histopathological examinations. Ligation and transection of the pedicle took 2 to 4 minutes. The vessels of the pedicle ranged in diameter from 3 to 12 mm. In two sheep, overzealous stripping of perivascular tissue from the renal pedicle prior to placement of a triple staggered row of staples resulted in mild hemorrhage from the renal stump. This was controlled by placing a second triple staggered row of staples proximal to the first. It was concluded that ligation of the renal pedicle could be performed rapidly, effectively, and safely in healthy sheep using the correctly applied mechanical stapler. It is inferred that a similar technique would be applicable to other species including man. PMID- 3344564 TI - Adherence of urease-induced crystals to rat bladder epithelium. AB - Apart from urine supersaturation with respect to struvite and calcium phosphate caused by urease-producing microorganisms, retention of formed crystals in the urinary tract is necessary for the formation of infection stones. This study was performed to investigate the role of the mucous coat lining the urothelium in the adhesion of urease-induced crystals. Removal of this glycosaminoglycan-containing layer from rat bladders increased the adherence of struvite and calcium phosphate crystals 5-6 times compared to that in intact rat bladders. Heparin completely restored the antiadherence capacity while chondroitin sulphate had a very weak restorative effect and human urine had no restorative effect. These findings support the view that the mucous coat is of importance in preventing retention of urease-induced crystals. PMID- 3344566 TI - Osseous choristoma of the ciliary body in guinea pigs. PMID- 3344567 TI - Pulmonary amyloidosis in a dog. PMID- 3344568 TI - Turbinate osteoporosis in pigs following intranasal inoculation of purified Pasteurella toxin: histomorphometric and ultrastructural studies. AB - Turbinate osteoporosis, induced by intranasal inoculation of purified toxin isolated from serotype D Pasteurella multocida, was investigated in 3- to 5-week old, caesarean-derived, colostrum-deprived, isolation-reared pigs. Marked bilateral reduction in relative volume of trabecular bone occurred in osseous cores of turbinates of toxin-treated pigs relative to control pigs on post inoculation day (p.i.d.) 3, 6, 9, 12, and 15. The fractional resorptive surface along turbinate bone was greater in toxin-treated pigs when compared to controls on p.i.d. 3 and 6. A significant decrease in resorptive surface occurred over time in toxin-treated pigs, whereas the fractional resorptive surface was constant over time in control pigs. Osteoclasts in medullary spaces separating bony trabeculae of turbinates were abundant in toxin-treated pigs and scant in controls on p.i.d. 3, 6, and 9. Degeneration and necrosis of bone forming cells, principally osteoblasts, were progressively more extensive with time and were associated with decreased mineralization and reduced thickness of osteoid and woven bone matrix. Osteoclasts along resorptive surfaces of turbinate bone in toxin-treated pigs had more abundant, more highly vacuolated cytoplasm, a more prominent microvillous border, and a greater number of nuclei per cell than osteoclasts from control pigs on p.i.d. 3 and 6. We conclude that this Pasteurella toxin stimulates osteoclastic osteolysis and inhibits osteogenesis in turbinates by causing degeneration and death of osteoblasts. PMID- 3344569 TI - Chordomas in Fischer 344 rats. AB - Tissue sections and records of 56 rats with chordoma, identified in the National Toxicology Program's (NTP) data base of approximately 115,000 rats, were examined to determine morphological characteristics, incidence, and aspects of biological behavior. Chordomas occurred in aged rats, originated predominantly in lumbosacral vertebrae, were highly malignant, occurred three times more often in male versus female rats, and commonly produced bilateral posterior paresis, paralysis, and/or distention of the colon and rectum. PMID- 3344571 TI - Unusual pelvic endocrine tumors of APUD cell origin in CBA mice. PMID- 3344570 TI - Veno-occlusive disease of the liver in captive cheetah. AB - Liver tissues from 126 captive cheetah were evaluated by light microscopy and histochemistry; eight animals were evaluated by electron microscopy. The main hepatic lesion, a vascular lesion resembling veno-occlusive disease (VOD) of the liver and characterized by subendothelial fibrosis and proliferation of smooth muscle-like cells in the central veins, was seen in 60% of the sexually mature cheetah. Although this hepatic vascular lesion was seen in cheetah as young as 1 year of age, the most severe lesions, usually associated with liver failure, were found in cheetah between the ages of 6 and 11. There was no sex predisposition, and in approximately 40% of the VOD cases, liver disease was not suspected clinically or at necropsy. VOD was found in other felidae, especially in the snow leopard. High levels of vitamin A in livers, as well as in diets of the cheetah, could be a contributing factor in the development of VOD in some groups of cheetah. PMID- 3344572 TI - Spontaneous storage-like disease in a rabbit. PMID- 3344573 TI - Simonsiella in ulcers in the lip of a dog. PMID- 3344574 TI - Encephalomyelitis in a dog caused by Baylisascaris infection. PMID- 3344575 TI - Disseminated pseudallescheriasis in a dog. PMID- 3344576 TI - Hepatic coccidiosis in a calf. PMID- 3344577 TI - [Clinical experiences with digital video image analysis procedures in the assessment of endoscopic ENT video findings]. AB - Recent developments in data processing enable digital information to be obtained from video frames, leading to the possibility of computerised analysis of endoscopic ENT videos (e.g. in laryngology). Two simple pilot systems ("Genlock Computer with Superimposer" and "Videodigitizer") are presented, as basis for a discussion of the advantages and disadvantages of these methods. PMID- 3344579 TI - Progress in the treatment of bile duct cancer: multidisciplinary approach. PMID- 3344578 TI - [Prevention of post-puncture complications by rotation of the puncture needle by 90 degrees]. AB - We investigated whether the incidence of post-lumbar puncture headache could be reduced by using a new technique. By rotating the puncture needle the spinal meninges become penetrated with the bevel adjusted parallel to the main fibre direction. Therefore the fibres are only dissociated and not cut. We used this method in 20 patients and only 2 of them complained of headache. By contrast 14 out of another group of 20 patients suffered from headache after conventional lumbar puncture. These results demonstrate that post-lumbar puncture headache can be prevented in a high percentage of patients without using special puncture needles or sophisticated techniques. PMID- 3344580 TI - Primary endoscopic papillotomy (EPT) in patients with stones in the common bile duct and the gallbladder in situ: a 5-8-year follow-up study. PMID- 3344581 TI - A comparison of flexible and rigid endoscopy in evaluating esophageal cancer patients for surgery. PMID- 3344582 TI - Surgical anatomy of the hepatic hilum with special reference to the caudate lobe. PMID- 3344583 TI - The role of preoperative biliary decompression in the treatment of bile duct cancer. PMID- 3344585 TI - Severity and types of head trauma among adult bicycle riders. PMID- 3344584 TI - Internal radiation for bile duct cancer. PMID- 3344586 TI - New technologies in diagnosis and classification of malignancy. PMID- 3344587 TI - Metabolic and kinetic aspects of toxicological studies. 19 May 1987, Paris, France. PMID- 3344588 TI - Plasma and tissue binding as determinants of drug body distribution. Possible applications to toxicological studies. AB - 1. Drugs are distributed through all body tissues via blood circulation. Consequently, most drugs rarely elicit one specific pharmacological effect but more generally have several, in different tissues. 2. In other words, drug effects are not unique or isolated, because drug distribution is not selective. Thus, considering a drug with a given liposolubility, its quantitative distribution in the body may be predicted in taking into account the physico chemical properties of the compound and the blood flows and the lipid contents of the different tissues and organs it will reach. 3. This paper attempts to show that plasma binding can influence the tissue distribution of drugs and may be applied to the minimization of toxic effects by decreasing the amounts of drug reaching the relevant tissues. 4. The value of an early determination of drug binding in human blood will be emphasized. This is justified by the fact that tissue distribution of drugs does not vary greatly between species whereas plasma binding may show important inter-species differences. Thus different plasma binding in humans may lead to large variations in tissue distribution as compared with experimental animals. PMID- 3344589 TI - An introduction to metabolic and kinetic aspects of toxicological studies. PMID- 3344590 TI - The pharmacological and toxicological significance of the stereochemistry of drug disposition. PMID- 3344591 TI - Extrapolation of preclinical pharmacokinetic data to therapeutic drug use. AB - 1. Preclinical in vivo and in vitro studies are fundamental to the safe and effective development of new drugs. 2. Pharmacokinetic and metabolic research is essential to a better understanding of the pharmacological and toxicological activities of drugs and their metabolites. 3. Data generated by such a strategy can be used to improve Phase I trials, particularly those for anticancer drugs. 4. Human and animal in vitro models are potentially powerful preclinical tools in: (i) The prediction of the pharmacological behaviour of analogues belonging to the same family, e.g. vinca alkaloids; (ii) The selection of the animal species most closely related to humans on the basis of metabolic pattern; (iii) The assessment of the duration of drug action--particularly those drugs exhibiting different metabolic clearances (e.g. benzodiazepines); (iv) The understanding and prediction of drug interactions, i.e. those described for cyclosporin A and macrolide antibiotics; and (v) The explanation of the metabolic origins of interindividual variabilities in pharmacological activity. PMID- 3344592 TI - Biopharmaceutical studies, a key to better toxicology. PMID- 3344593 TI - [Evening shift in Mozambique]. PMID- 3344594 TI - [Custom-made reducing with tape measure and computer. Interview by Viveka Holmertz]. PMID- 3344595 TI - [Team work is the same in drag racing and in nursing. Interview by Jan Thomasson]. PMID- 3344596 TI - Butorphanol tartrate: research advances in multiple clinical settings. PMID- 3344597 TI - Urological applications of butorphanol tartrate: postoperative pain and renal colic. AB - The analgesic efficacy and safety of butorphanol tartrate are discussed in 2 groups of patients who underwent urological procedures. The first group of 83 patients is presented as a retrospective review of the postoperative use of butorphanol. The second group of patients was involved in a double-blind, randomized comparative trial of butorphanol (2 or 4 mg) and meperidine (80 mg) for the relief of moderate to severe pain due to renal colic. Eighty-three patients with documented upper urinary tract calculi were evaluated for efficacy; 120 patients were evaluated for safety. Butorphanol 4 mg (i.m.) was more effective than butorphanol 2 mg (i.m.) and equivalent to meperidine 80 mg (i.m.). There were no statistically significant differences among the three treatment groups in regard to side effects. Overall, in the urology patients studied, butorphanol was found to be an effective and well tolerated agent that possesses important safety advantages when compared with the narcotic analgesics. PMID- 3344598 TI - Patient-controlled analgesia using butorphanol for postoperative pain relief: an open-label study. AB - Patient-controlled analgesia (PCA) has been studied extensively for the treatment of postoperative pain using narcotic analgesics. Butorphanol, a nonnarcotic injectable analgesic, has not previously been investigated using this drug delivery mechanism. Twenty-five patients undergoing general abdominal surgery and general anesthesia used a PCA device with butorphanol as the analgesic agent. Most patients (84%) were able to obtain excellent postoperative pain relief. The role of butorphanol in the management of postoperative pain should be expanded to include patient-controlled drug delivery. PMID- 3344599 TI - Double-blind comparison of butorphanol and morphine in patient-controlled analgesia. AB - In this study, the patient-controlled analgesia (PCA) technique was used to compare the suitability of butorphanol with that of morphine in relieving postoperative pain. Twelve patients, 19-77 years old, who had abdominal surgery, used the PCA device through the first 24-hour postoperative period. Results showed that all patients expressed satisfaction with the PCA technique. Analysis of the degree of discomfort according to the verbal description scale, recordings of respiratory rate, and assessment of sedation status showed no significant differences between patients who received butorphanol and those who received morphine. Patients were able to maintain acceptable analgesia with minimal sedation. There were no adverse side effects reported with butorphanol. PMID- 3344600 TI - Outpatient sedation for oral surgery: a comparison of butorphanol and fentanyl. AB - Third molar surgery in the oral and maxillofacial surgery office has been a predictable model for evaluating the efficacy of sedatives and analgesics. In this setting, butorphanol plus diazepam and fentanyl plus diazepam were compared for surgical effectiveness and postoperative recovery. The comparison of butorphanol to a known sedative combination was clinically very satisfactory. It appears from this data that butorphanol has a pharmacologic place in outpatient conscious sedation. PMID- 3344602 TI - Pulmonary complications after upper abdominal surgery: their prevention with intercostal blocks. AB - A prospective study of postoperative pulmonary complications (PPC) appearing during the hospital stay was carried out in 417 patients undergoing surgery through a subcostal or midline incision. Postoperative pain was relieved either by intercostal block and centrally-acting analgesics on demand or by centrally acting analgesics alone. Pulmonary complications were diagnosed from combined physical and radiological signs. After biliary surgery through a subcostal incision, PPC were less frequent (P less than 0.05) in patients receiving intercostal blocks (6%) than in those given centrally-acting analgesics (11%). After surgery through a midline incision, the complication rate was higher, 15 57%, and was related to the type of surgery, the highest incidence being found after partial gastrectomy and operations for malignancy, and no significant reduction in the rate of PPC after intercostal blocks with this incision was found in any age group. Indeed, an increased rate of PPC was found in our patients over the age of 60 who had received bilateral intercostal blocks. Irrespective of the type of incision, surgery or method of postoperative pain relief, the patients with PPC more often had respiratory or other disorders preoperatively or a surgical complication intra- or postoperatively than those with normal postoperative recovery. Predisposing physical factors and high age were more common among the patients developing PPC in spite of treatment with intercostal blocks compared to those without such treatment. PMID- 3344601 TI - Influence of age on the pharmacokinetics of butorphanol. AB - Butorphanol kinetics were studied in 8 young (23-34 years of age) and 9 elderly (65-79 years of age) healthy male subjects following a single, intravenous 2-mg dose of butorphanol tartrate. Plasma and blood concentrations collected over 24 h were analyzed by a second antibody radioimmunoassay for unchanged drug. Systemic blood clearance (21.29 +/- 7.18 ml/min/kg), apparent steady-state volume of distribution (9.02 +/- 2.40 liters/kg), distribution half-life (7.67 +/- 4.66 min), and the blood/plasma concentration ratio (1.21 +/- 0.36) in the elderly did not differ from those in the younger subjects. However, the terminal elimination half-life was significantly prolonged in the elderly (5.51 +/- 2.49 versus 3.67 +/- 0.52 h, p less than 0.05). Positive correlations between age and terminal elimination half-life and volume of distribution were noted. Our data suggest that young and old subjects attain similar plasma concentrations after single doses; however, longer dosing intervals may be necessary for multiple dosing in the elderly. The appropriate dosing interval for butorphanol needs to be assessed in elderly patients. PMID- 3344604 TI - Malignant hyperthermia susceptibility confirmed in both parents of probands. A report of three Austrian families. AB - From 1976 to 1986, 79 cases of suspected malignant hyperthermia (MH) were reported to the authors' institution. A total of 233 muscle biopsies was done in 66 families. The mother and father of the proband were investigated in 44 families; in three of these, both parents of probands gave positive test results. These three families, all from Vorarlberg, a secluded mountain area, represent 4.5% of all our MH-positive families (n = 61) and 7.3% of all MH-positive families where both parents had been tested (n = 41). This observation might be explained by: 1) a much higher incidence of MH in this part of Austria, and 2) a different test policy, as at the authors' institution, if possible, both parents are investigated, even if there is a positive test result in one of them. It is concluded that family investigations of MH susceptibility should always include both parents of a proband. PMID- 3344603 TI - Effects of ketamine on liver blood flow and hepatic oxygen consumption. Studies in the anaesthetised greyhound. AB - The effects of three increasing doses of ketamine on the blood flow to, and oxygen consumption of, the liver, were studied in seven anaesthetised greyhounds. Hepatic arterial and portal venous blood flows were measured continuously using electromagnetic flow probes, and mean arterial pressure and cardiac output monitored as appropriate. Ketamine, even at the highest dose, had little effect on the blood flow to the liver: hepatic arterial blood flow and portal venous blood flow did not differ significantly from their baseline values. However, the oxygen delivery to the liver decreased due, probably, to an increase in oxygen consumption by the pre-portal organs. PMID- 3344605 TI - Comparison of costs of different anaesthetic techniques. AB - The costs of anaesthetic drugs, intravenous agents as well as gases, were studied for different anaesthetic techniques in a medium-sized operative procedure, cholecystectomy. Three anaesthetic breathing systems were used: a non-rebreathing system, a circle absorber system with medium fresh gas flows of 3-6 l/min, and a low-flow circle system. Anaesthesia without volatile inhalation agents used with a low-flow technique was the least expensive, and anaesthesia with isoflurane in a non-rebreathing system was the most expensive. The costs of anaesthesia without volatile inhalation agents in a non-rebreathing system, enflurane anaesthesia in a circle system with medium fresh gas flows, and isoflurane anaesthesia with low flow technique were similar. PMID- 3344606 TI - Relations between irrigant absorption rate and hyponatraemia during transurethral resection of the prostate. AB - The serum sodium concentration (S-Na) and the volume of irrigating fluid absorbed were measured during 10-min periods in the course of 85 transurethral resections of the prostate (TUR). The hyponatraemic response to absorption of the irrigant was found to be dependent on the volume of fluid absorbed and the time required for the absorption. During the first 10 min of absorption the distribution volume of the irrigating medium was roughly equal to the extracellular space, but after this period the volume was greater. The sodium level could be compensated for further absorption to the extent of 200-300 ml irrigant per 10-min period; when this volume was exceeded, hyponatraemia was aggravated. The results indicate that in the development of the very low S-Na level typical of a severe TUR reaction, a rapid massive absorption is a more important factor than a large total absorbed volume. PMID- 3344607 TI - Accidental puncture of the right lymphatic duct during pulmonary artery catheterization. A case report. AB - A case of an accidental placement of the introducer sheath of a Swan Ganz catheter into the right lymphatic duct during right internal jugular vein catheterization is presented. This rare complication has to be reported, because the choice of the right internal jugular vein for central venous catheterization has been strongly recommended, with special concern being paid to the avoidance of any thoracic duct injury. No deleterious complications were observed either in the immediate or in the later postanaesthetic period. PMID- 3344608 TI - Development of the subfornical organ and area postrema of the male albino mouse. Karyometric effect of neonatal and prepuberal castration. AB - We have studied the karyometric development of the nuclei of the ependymal cells and neurons of the subfornical organ and the area postrema in the male albino mouse from the 5th to the 190th postnatal day. We have found similar patterns of development in both although the area postrema showed more significant postnatal oscillations than those of the subfornical organ, suggesting a more intimate chronological relationship to gonadal development. We have furthermore analyzed the development in two experimental groups: in the one animals were castrated at birth, in the other, castration was made on the 20th postnatal day. We have found that neonatal castration produced a significant decrease of nuclear sizes; this was more evident in the subfornical organ than in the area postrema in earlier stages of development while the response was similar in both at peripuberal ages. The response to prepuberal castration was similar in both organs. PMID- 3344609 TI - Postpubertal changes in the histomorphometric characteristics of the uterus of the indigenous West African pig. AB - The epithelial height and myometrial and endometrial characteristics of the fundus, corpus and neck regions of the uteri of 28 virgin West African indigenous gilts in four age groups (6-8, 10-12, 16-18 and 20-22 months) were histometrically evaluated. Though regionally stable, the height of luminal epithelial cells was, respectively, reduced and enhanced in the fundus and neck regions by 10-12 months. The myometrium was thinner in the fundus and was severely reduced in the corpus region in gilts aged 16-18 months. Contrarily, the endometrium was regionally stable in thickness but underwent some thickening in the corpus of 16 to 18-month-old gilts. The respective occurrence of muscular and glandular tissues in the myometrium and endometrium was regionally influenced while older gilts had more circular muscles than the others. Generally, over 70% of the glands and 60% of the muscles were complex glands and longitudinal muscles, respectively. Results depict the nonuniform growth rates of different uterine tissues in the different regions and suggest that the improvement in the litter-carrying capacity of the uterus in these pigs continues well after puberty. PMID- 3344610 TI - Annulate lamellae as a precursor or a product of paired cisternae in human adenomatous parathyroid cells. AB - Clusters of chief cells from a fragment of human parathyroid adenoma possess relatively few rough endoplasmic reticulum (RER) cisternae with scattered annulate lamella (AL) pores in cytoplasmic sectors close to the nucleus. Some of these cisternae exhibit winding profiles with smooth segments lying very close to the outer nuclear membrane. Other groups of cells exhibit well-developed stacks of RER either in continuity with or separated from AL. Two other tumor fragments show chief cells with few RER cisternae scattered in the cytoplasm and possess stacks with various amounts of AL and/or paired cisternae (PC), occasionally at perinuclear sites. Compartmental continuity between AL and PC is a frequent finding. Pore density in AL varies considerably between the stacks from different cells. PMID- 3344611 TI - Morphometric analysis of frozen transverse sections of human skeletal muscle taken post-mortem. AB - Necropsies were obtained from 5 muscles from 5 young women. The muscles subjected to morphometrical analysis were the deltoid, brachial biceps, vastus lateralis, gastrocnemius and soleus. Results of measurements taken indicate significant differences in fibre sizes and fibre type composition in analogous muscles between individuals and between different muscles within individuals. Differences were also encountered in muscle fibre size during rigor mortis for up to 48 h after death. Our results suggest that the fibre size variability between individuals determined from necropsy samples will contain a component of induced variation not found in muscle biopsies. PMID- 3344612 TI - Morphology of the lumbar vertebral canal. AB - In a series of 215 anteroposterior X-ray films, a study was made of the horizontal distance between the pedicles of each lumbar vertebra, first of all sequentially, describing the morphology adopted by the lateral limits of the canal, and secondly determining the absolute value for each level separately and in relation to the variables of sex and age. The absolute value of this distance at each level is related to the thickness of the pedicles and the width of the vertebral bodies of L3 and L4. The values obtained were tested with the appropriate statistics in each case. PMID- 3344614 TI - Marginal and folliculo-stellate cells of the pituitary gland of the rat. A comparative morphometric study in lactating animals. AB - We examined non-granulated pituitary cells (folliculo-stellate cells and anterior and posterior marginal cells of the pituitary cleft) in lactating and virgin female rats by means of electron microscopy and morphometry. Ultrastructure and morphometric parameters of the cells lining the pituitary cleft were similar in the two groups of animals. On the contrary, folliculo-stellate cells showed a marked nucleocytoplasmic activation in lactating rats in the electron microscope, which was confirmed by morphometric measurements. These results are not consistent with the hypothesis that the three cell types share the same reactivity during pituitary hyperfunction and that they have a common function, as suggested by purely morphological studies in various endocrine conditions. We believe that quantitation of cell response during such stimuli could be useful to further elucidate this matter. PMID- 3344613 TI - Castration cells in rat adenohypophysis after long-term alcohol consumption. AB - Histological and ultrastructural changes of hypophyseal gonadotropic cells of rats which received a 15% solution of ethyl alcohol for 6 months were studied. Light microscopy revealed hyperplasia and hypertrophy of these cells; some contained a vacuole of varying size. Ultrastructural analysis showed that this vacuole originated from, and anastomosed with, dilated cisternae of the granulated endoplasmic reticulum. Vacuolated cells in the pituitary of alcoholized rats were identical with cells observed after surgical or chemical castration. The development of these alcohol-induced castration cells is achieved in four stages. The first stage was characterized by beginning hydropic degeneration and other still reversible alterations. Cells in the second and third stages seemed already irreversibly on their way to decay. The fourth stage was represented by typical signet-ring cells. Our results offer a morphological basis to the adoption of a biphasic effect of alcohol on gonadotropic secretion. PMID- 3344615 TI - Partial degeneration of autonomic nerves of the heart of methotrexate-treated guinea pigs. AB - In the present investigation partial degeneration of adrenergic and cholinergic nerves of the heart of guinea pigs following methotrexate treatment has been reported. No appreciable change was observed in the autonomic nerve fibres after 3 days of treatment. However, after prolonged treatment some nerve fibres showed signs of degeneration and a few adrenergic and cholinergic nerve fibres had disappeared. PMID- 3344616 TI - [Quantitative and morphological studies of retinal development in mice with trisomy 19]. AB - To investigate the development of the retinal layers, the eyes of mice with trisomy 19 have been examined by light microscopy between the 2nd and 15th postnatal day. The diameter of the eye, thickness of the entire retina and both relative thickness and nuclear density of each of the retinal layers have been measured and compared to those of chromosomally balanced control animals. Malformations of the eye, alterations of cell morphology or disturbed lamination can not be observed. Retinal differentiation of trisomy 19 mice is delayed by approximately two days. The development of all cellular constituents, i.e., of both neuroectodermal and mesenchymal origin, is retarded accordingly. The eyes of trisomy 19 mice are of reduced size. The relative thickness of each retinal layer follows a normal growth pattern; there is no indication for a selective impairment of the development of one particular layer. With the exception of the ganglion cell layer, nuclear densities of each retinal layer do not differ from those of control mice. The comparison of nuclear densities in the ganglion cell layer suggests that in trisomy 19 mice fewer postmitotic cells differentiate into mature retinal cells. PMID- 3344617 TI - Ultrastructural and immunocytochemical changes of prolactin cells of grafted pituitary after the injection of dopamine in the albino rat. AB - Anterior pituitary glands were homografted into the anterior chamber of the eye in female rats. The pituitary grafts survived and were well vascularized three weeks after the transplantation. The prolactin cells were morphologically active as shown by their well-developed Golgi complexes and granular endoplasmic reticulum and the exocytosis of secretory granules. The injection of dopamine into the common carotid artery of the graft-bearing rat rapidly suppressed the granule extrusion and then gradually induced a remarkable morphological atrophy in the prolactin cells. PMID- 3344618 TI - Skeleton, blood vessels and viscera: overlooked targets in fetuses of small species during the external examination for teratogenicity assessment. AB - Due to the translucency of the skin and underlying soft tissues, the external examination of near-term mouse fetuses can be extended to parts of the skeletal, visceral and vascular systems which are not taken into account in the protocols of teratogenicity tests. The importance of such visualization for improving the accuracy of such tests is discussed. PMID- 3344619 TI - Femoral expansion in the adult male rat. AB - The length, total and cortical widths at midshaft, and robusticity of femora were measured in growing and mature male Holtzman rats. Analysis of covariance revealed significant differences in the regression coefficients (slopes) between young rats (1-4 months) and adult rats (5-16 months), indicating that, for a given increment in femoral length, young rats have a smaller increment in total femoral width than do adult rats. In addition, the results indicated that femoral expansion occurs in adult male Holtzman rats (5-16 months of age) without cortical thinning or loss of bone mass. PMID- 3344620 TI - Atresia of the right atrial ostium of the coronary sinus. AB - A case of asymptomatic congenital occlusion of the ostium of the coronary sinus is described. The myocardial venous drainage was maintained via a persistent left superior vena cava as well via ectatic, widened atrial veins of the dorsal wall of the left atrium. The study shows that complete ostial occlusion of the coronary sinus does not reduce cardiac venous drainage. The view of the literature allows a comparison with the comprehensive classification of coronary sinus anomalies. PMID- 3344621 TI - Synchondroseal growth in the first cervical vertebra of the rat. AB - Growth and remodelling of the first cervical vertebra were studied in the rat by means of biometry, vital staining (alizarin red S and oxytetracycline), and histology. The measurements showed a change in the ratio of the dorso-ventral to the transversal diameter in the lumen after obliteration of the dorsal synchondrosis. The pattern of labelling between the three segments of the vertebrae joined by synchondroses in the young animals indicated that expansion of the vertebral lumen took the form of a displacement of all three parts making up the bony ring. After closure of the dorsal synchondrosis the two ventral ones were still active and the lumen size increased more in the dorso-ventral direction than transversally. Alizarin red S and oxytetracycline tended to persist in the ventral part of the vertebra, while the staining almost disappeared from the dorso-lateral segment. Resting lines were found laterally to the ventral synchondroses in haematoxylin and eosin stained sections, but not in the ventral segment between the cartilages. The growth of the rat atlas is the result of an early rapid cartilage-mediated expansion of the vertebral lumen in conjunction with the growth of the spinal cord and, at a later age, mainly of a displacement of the ventral vertebral segment, leading to the final form of the vertebra and its lumen. PMID- 3344622 TI - The incidence of multiple meningiomas--do solitary meningiomas exist? AB - Since the advent of computed tomography (CT) the recognition of the occurrence of multiple intracranial meningiomas (MIM) in the same individual has been on the increase. In our material the incidence of MIM at first assessment of CT films was 20%, with distant multiplicity prevailing over the regional one. This incidence will probably change in the course of time as MIM develop not only concurrently but also consecutively. On the other hand our surgical macroscopic incidence of regional multiplicity alone was 49%. The discrepancy between the CT and surgical findings prompted us to reevaluate the CT studies of 100 consecutive patients. This reevaluation demonstrated: 1. in two cases, small meningiomas were overlooked at first assessment; 2. nineteen cases of solitary globoid meningiomas seemed to be the consequence of the coalescence of adjacent smaller masses. Thus, the CT incidence of MIM increased to 40%, with regional multiplicity prevailing over the distant one. The authors think that the aforesaid findings question the very existence of solitary meningiomas as a pathological entity. They would be the end product of a coalescence of multiple adjacent smaller growths. Accordingly, a more aggressive surgical approach is suggested to include the resection of a generous fringe of dura mater around the main tumour. As this is not always possible, or too risky, a comprehensive complement to surgery like radiotherapy could be given a reasonable randomized trial. PMID- 3344624 TI - Formation and propagation of brain oedema fluid around human brain metastases. A CT Study. AB - Computerized tomography (CT) was used to examine the time-course of the propagation of extravasated contrast medium from small brain metastases into the peritumoural oedematous white matter, following infusion of 200 ml of meglumine amidtrizoate for 3 hours. Four patients with a metastatic brain tumour were examined. CT scans at identical levels were taken 1.5, 3, 6, 9, and 12 hours after start of contrast infusion. Following 4-7 days of dexamethasone treatment (8-12 mg/day i.v.) the examination was repeated. A contrast-enhanced area was observed surrounding the clearly delineated tumours, expanding gradually in a circular fashion into the peritumoural white matter oedema. The expanding circular enhancement was measured planimetrically on the various scans. From these values, the increase in radius/hr respectively in volume/hr was calculated, assuming a spherical geometry. This enabled a determination of the rate of oedema fluid formation and of the speed of oedema fluid propagation. The formation rate of oedema fluid amounted to 0.5-3.2 ml/hour and the speed of oedema fluid spreading to 1.9 mm/hour. Following treatment with dexamethasone the formation rate of oedema fluid is reduced by 30-50%. The important clinical implications of these new findings are discussed. PMID- 3344623 TI - Cystic meningiomas. AB - Twenty-two cases of unusual intracranial meningioma associated with a cyst are reported and 144 published cases reviewed. The complex mechanisms leading to the formation of the cyst within the meningioma are analyzed on the basis of the surgical and histopathological evidence. The neuroradiological features (Computed Tomography and Angiography) which supply a correct preoperative diagnosis are discussed. It is clear from the literature how difficult preoperative diagnosis is, being possible only in 38% of cases with CT scanning and in 13% with angiography. It is necessary to remove not only the solid portion of the meningioma but also the cyst wall in order to prevent a recurrence. This is technically difficult for the type II intratumoural variety of Nauta's classification. PMID- 3344625 TI - The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs. AB - The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nifedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10(-6) M HA 1077 for the "intracranial" basilar and middle cerebral arteries, while a 10(-5) M was needed to obtain the same effect for the "extracranial" common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the "two haemorrhage" model of Varsos et al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5-3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20 30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344626 TI - Microsurgical anatomy of the arteries of the pituitary stalk and gland as viewed from above. AB - The microsurgical anatomy of the arteries of the pituitary stalk and gland as viewed from above was studied in 50 adult cadaveric hemispheres using the operating microscope. There were three types of vessels to the pituitary from above: the superior hypophyseal artery originating from the internal carotid artery, the infundibular artery from the posterior communicating artery, and the prechiasmal artery from the ophthalmic artery. The superior hypophyseal artery originated from the medial to posterior aspect of the internal carotid artery. The average number of vessels of the superior hypophyseal artery was 2.2 per hemisphere, and the diameter was 0.25 mm on average. The majority (76%) of superior hypophyseal arteries arose from the proximal half of the segment between the origins of the ophthalmic and posterior communicating arteries of the internal carotid artery. The infundibular artery originated mainly from the medial side (69%) of the posterior communicating artery. Its diameter was 0.22 mm, and number 0.23 per hemisphere. The number of prechiasmal arteries was 0.06 per hemisphere. As a result, there were on average 2.5 vessels per hemisphere, totally 5 per brain, with the average diameter 0.25 mm, supplying the pituitary stalk and gland from above. The clinical application of these anatomical data to the diagnosis and treatment of suprasellar tumours and carotid-ophthalmic aneurysms is discussed. PMID- 3344628 TI - Functional recovery in neurological disease. PMID- 3344627 TI - Astereognosis as a presenting symptom in cervical meningioma. AB - Three unusual cases with astereognosis caused by cervical meningioma are presented. Astereognosis of subcortical origin has been reported several times. According to these reports, the causative lesion was confined to the area extending between the lower brain stem and the fourth cervical vertebra, thus suggesting that a sensory centre for stereognosis could be confined within these well defined anatomical limits, and that therefore a lesion in this area could lead to astereognosis. It is assumed in this paper that the lesion involves the sensory system of the Nucleus Cervicalis Lateralis. Fibres from the spinothalamic tract, a specialized sensory pathway, ascend from the palms of the hands to this nucleus. From this nucleus arise fibres which decussate and reach the Ventral Posterolateral Nucleus of the thalamus. It is likely that a lesion of the nucleus itself or its related sensory tracts may cause astereognosis. PMID- 3344629 TI - Functional recovery in diseases of the nervous system. PMID- 3344631 TI - Facial dyskinesias. PMID- 3344630 TI - What do we learn from recovery from aphasia? AB - 1. Recovery rates are different from outcome measures, and therefore paradoxically positive correlation between the recovery of comprehension and lesion size can be found particularly in Broca's aphasia or in populations that are skewed toward nonfluent aphasics. 2. Outcome, in terms of recovery from aphasia, correlates significantly with lesion size in the expected direction regardless of initial severity for the total aphasic group, but not as much in Wernicke's aphasia. 3. Outcome correlates well with initial test scores, but, particularly in Broca's aphasics, lesion size is as good a predictor as initial severity. 4. The rate of recovery differs in different types of aphasia, and Broca's aphasics recover most. 5. The initial recovery period between 0 and 3 months is significantly steeper than subsequent periods, but it does not correlate as well as outcome with lesion size. 6. Cerebral asymmetry or torque may be less typical in more recovered Broca's aphasics, but this failed to reach statistical significance and seems not be a factor for Wernicke's aphasics. 7. Age and gender are not as significant as lesion size and location. 8. Surrounding intact ipsilateral structures are more important for the recovery of some of the language functions, such as motor output and phonemic assembly, than homologous contralateral structures. Comprehension and semantic processing may have more contralateral or right hemisphere compensation than other language functions. PMID- 3344632 TI - Blepharospasm and cranial-cervical dystonia (Meige's syndrome): familial occurrence. PMID- 3344633 TI - Facial mannerisms and tics. PMID- 3344634 TI - Spasmodic dysphonia. PMID- 3344635 TI - Blink reflex in facial dyskinesia. PMID- 3344637 TI - Botulinum toxin in cervical dystonia. PMID- 3344636 TI - Acute pharmacologic tests in cranial dystonia. PMID- 3344638 TI - Botulinum toxin injection therapy for hemifacial spasm. PMID- 3344639 TI - "The eagle and the arrow". Madison Avenue medicine. PMID- 3344640 TI - Opsoclonus and ataxia accompanying acute gastroenteritis. PMID- 3344641 TI - A lingering question. PMID- 3344642 TI - Something about taste. PMID- 3344643 TI - Weight cycling. PMID- 3344644 TI - New wine, old wineskins. PMID- 3344645 TI - Diagnostic schema for somatic and psychologic complaints. AB - The patient with somatic complaints may have a "clear-cut" medical condition or a somatoform disorder. The patient with psychologic complaints may have a "clear cut" psychiatric disturbance or an organic brain disorder. Medical conditions may be worsened or complicated by psychologic factors. The challenge to the physician is to discover which category best encompasses the patient's symptoms so that a rational plan of management can be devised. PMID- 3344646 TI - Home-based renal dialysis. AB - About 20 percent of chronic dialysis patients receive treatment in their homes. An increasing number of these patients choose peritoneal dialysis. Physicians should be aware of the techniques and possible complications of home-based dialysis so that they can assist patients in choosing a form of dialysis and can help manage problems if they arise. An understanding of the technical and psychosocial problems is also necessary. PMID- 3344647 TI - Radon. PMID- 3344648 TI - Prevention of medical emergencies during air travel. AB - The growing number of people who travel by air make it increasingly important for family physicians to be able to advise patients on the medical risks involved. Cardiovascular and pulmonary problems are the most common reasons for excluding air travel. Hypoxia in the cabin may be dangerous for patients with unstable angina, severe congestive heart failure and chronic obstructive pulmonary disease. PMID- 3344649 TI - Sexuality in the mentally retarded patient. AB - Physicians who provide care for mentally disabled patients are often confronted with perplexing decisions involving sexuality, contraception and marriage. In the face of uncertainty, the physician may take the path of least resistance, which may not be the best solution for the patient. For example, it is not widely known that marriages among mentally retarded individuals can provide stability and considerable satisfaction. PMID- 3344650 TI - Chigger relief. PMID- 3344651 TI - Drug management of hypercholesterolemia. PMID- 3344652 TI - EEGs and Alzheimer's disease. PMID- 3344654 TI - Falsely elevated acid phosphatase. PMID- 3344653 TI - Bacterial meningitis rates. PMID- 3344655 TI - Thromboxane synthetase inhibition reduces ventricular irritability after coronary occlusion and reperfusion. AB - Reperfusion of ischemic tissue is responsible for production of metabolites with deleterious local vascular effects. Thromboxane A2, a potent vasoconstrictor and platelet aggregator, has been implicated as a mediator of the "reperfusion injury." We studied the effect of an experimental thromboxane synthetase inhibitor, OKY-046, on coronary sinus thromboxane levels, ventricular irritability, myocardial contractility, infarct salvage, and histologic features of reperfusion. Sixteen sheep were randomized to OKY-046, 3 mg/kg, or saline vehicle before 3-hour occlusion and subsequent reperfusion of the left anterior descending artery. The OKY group demonstrated less ventricular irritability as measured by incidence of ventricular fibrillation and necessity for countershock to reverse tachyarrhythmias. Coronary sinus thromboxane levels were significantly lower in the OKY group compared with the control group. There is additional evidence to suggest that OKY increases infarct salvage and attenuates histologic features of microcirculatory damage. PMID- 3344656 TI - Serial nuclear magnetic resonance imaging of acute myocardial infarction with and without reperfusion. AB - To compare nuclear magnetic resonance (NMR) image-derived T1 and T2 changes during evolving infarction, 14 dogs were studied serially: (1) 1 to 2 hours after left anterior descending coronary occlusion, (2) 2 to 3 hours after coronary occlusion (n = 7) or in the first hour after reperfusion following 2 hours of occlusion (n = 7), and (3) 5 days and (4) 21 days after occlusion/reperfusion. In addition, the extent of T1 and T2 abnormalities was compared to the extent of infarction as determined histologically for each set of images. With sustained coronary occlusion, an increase versus control values (T1 = 351 +/- 11 msec; T2 = 41 +/- 2 msec) was observed in the second hour after occlusion (T1 = 448 +/- 51 msec; T2 = 51 +/- 8 msec), gradually reaching a maximum by day 5 (T1 = 490 +/- 64 msec; T2 = 63 +/- 9 msec). By 21 days, T1 had decreased to 427 +/- 43 msec and T2 to 55 +/- 11 msec. However, with myocardial reperfusion, an abrupt increase in both T1 and T2 occurred compared to prereperfusion values in the first hour after release of occlusion, from 445 +/- 32 msec to 555 +/- 65 msec and from 52 +/- 5 msec to 65 +/- 8 msec, respectively. Subsequently, T1 remained elevated whereas T2 normalized. Only on day 21 images was there a good correlation between the extent of T1 and T2 abnormalities and infarct size, in both nonreperfused (r = 0.87; p less than 0.05), and reperfused (r = 0.89; p less than 0.01) dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344658 TI - Sequential transvenous pacing and shock therapy for termination of sustained ventricular tachycardia. AB - Rapid ventricular pacing and transvenous shocks are both effective in terminating sustained ventricular tachycardia (VT) only in selected patients. We prospectively examined efficacy and safety of an algorithm for VT termination combining rapid ventricular pacing with low and moderate energy transvenous shocks in patients with sustained VT. Sixty-three VT episodes in 23 patients, mean age 64 +/- 12 years, were treated with the algorithm. Bursts of rapid ventricular pacing and transvenous shocks were delivered with a Medtronic 6880 catheter positioned in the right ventricular apex. VT episodes with cycle lengths greater than 270 msec (group A) were treated with sequential therapy with rapid ventricular pacing (90%, 80%, and 70% of VT cycle length), low energy transvenous shocks (0.5 to 2.7 J), and moderate energy (2.7 to 10 J) transvenous shocks. Rapid VT episodes with cycle lengths less than 270 msec (group B) were treated with moderate energy transvenous shocks directly. Forty-one of 48 (85%) VT episodes in group A and 6 of 15 (40%) VT episodes in group B were successfully terminated by this algorithm. There was no difference in clinical or arrhythmia characteristics between responders and nonresponders in either group A or group B to the algorithm. VT acceleration was observed in 12% of episodes in group A and in 47% of episodes in group B. We conclude that an algorithm combining rapid ventricular pacing with low and moderate energy transvenous shocks is effective for VT termination in episodes with a cycle length greater than 270 msec and can reduce the need for transthoracic cardioversion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344657 TI - Long-term prognosis of medically treated patients with vasospastic angina and no fixed significant coronary atherosclerosis. AB - The clinical course of 48 consecutive patients with vasospastic angina and minor coronary atherosclerosis (no stenoses greater than 50%) was analyzed during an average follow-up period of 47 months. The study group consisted of 37 men and 11 women. Patients were treated with usual doses of calcium antagonists. One patient died (2%) and three had myocardial infarctions (6%). Seventy-one percent were asymptomatic or had infrequent angina; 13% had recurrences but had periods of remission lasting at least 10 months. Only 16% had persistent angina. None of the clinical or angiographic findings at the time of diagnosis were predictive of myocardial infarction or death, and they could not separate angina-free patients from those with recurrences. Thus, vasospastic angina without fixed coronary narrowing has a good prognosis despite the possibility of recurrences. However, there is a slight risk of myocardial infarction and death. This fact should be considered if there are plans to discontinue treatment. PMID- 3344659 TI - Signal-averaged electrocardiograms in patients with atrial fibrillation or flutter. AB - The signal-averaged QRS complex that is prolonged because of low amplitude late potentials predicts ventricular tachycardia. This study investigated if signal averaged low amplitude atrial potentials predict atrial fibrillation or flutter (AFF). Low amplitude potentials were considered to be high-frequency, high amplitude P (HiFP) duration recorded between 50 and 250 Hz at 1.0 mm/microV amplitude minus unfiltered P (UnFP) duration at 0.1 mm/microV. In nine normals, HiFP averaged 115.6 msec +/- 9.8 SD. HiFP were wider in 26 control patients (133.5 msec +/- 15.7, p less than 0.005) but HiFP-UnFP (11.2 msec +/- 8.5) and signals less than 10 microV terminating HiFP inscription (21.7 msec +/- 23.4) were similar to normal values. Seventeen patients with paroxysmal or recently cardioverted AFF did not have significantly longer intervals than controls (HiFP averaged 138.8 msec +/- 23.0, HiFP-UnFP 13.2 msec +/- 9.3, and signals less than 10 microV 32.4 msec +/- 19.5). Therefore, signal-averaged P waves do not identify patients with AFF. PMID- 3344660 TI - Atrial automatic ectopic tachycardia due to an atrial tumor. AB - A dilated cardiomyopathy picture has been produced by rapid atrial and ventricular rates sustained for a long period of time in some patients. The ventricular tachycardias have in some instances been associated with ventricular tumors as the cause of the tachycardia. Once the tumor is removed, the tachycardia stops and the heart function improves. Atrial ectopic tachycardias also produce a similar picture, but have not been associated with atrial tumors. Such a case is presented with an atrial rhabdomyoma producing atrial ectopic tachycardia and a dilated, poorly contracting myocardium. The tumor was resected and the tachycardia was immediately abolished. Cardiac function quickly returned to normal. PMID- 3344661 TI - Arrhythmias after repair of secundum atrial septal defect: the influence of surgical modification. AB - A retrospective study performed in our institution showed a significant correlation between venous cannulation and the incidence of arrhythmias after atrial septal defect (ASD) repair. We now report the results of a prospective study in 50 children operated on for ASD with selective cannulation of the superior vena cava. ECGs and Holter recordings were made before and after surgery, with a mean follow-up of 2.6 years. We found a significant decrease in postoperative arrhythmias (p less than 0.05) after changing the cannulation technique. Severe arrhythmias, present in 10% of the children in the retrospective group, were not found in the prospective study. Six children had asymptomatic arrhythmias on the Holter recording 1 year after surgery. Three of them, however, already had arrhythmias before the operation. We conclude that the incidence and severity of arrhythmias after ASD repair can be reduced significantly by surgical modifications, at least for the follow-up period of this study. The long-term significance has to be awaited. PMID- 3344662 TI - Preliminary experience in the use of ultrafast computed tomography to diagnose aortic valve stenosis. AB - Eight patients, mean age 72 years, with aortic valve stenosis were studied by ultrafast CT 1 day after cardiac catheterization. After injection of radiographic contrast material through a peripheral vein, two contiguous eight-level R wave triggered cine mode scans in the short axis were acquired, starting above the aortic valve and continuing through the apex of the left ventricle. Seven of eight patients, all with calcified aortic valves, had a detectable central orifice. Catheterization-derived aortic valve areas were within 0.25 cm2 of the CT valve areas in six of seven. LV mass was measured by ultrafast CT in the eight patients with aortic valve stenosis (121.6 +/- 18.2 gm/m2) and was found to be significantly higher (p less than 0.0001) than that in a group of eight subjects with normal LV function, no history of hypertension, and normal ECGs (73.0 +/- 13.1 gm/m2). It is concluded that in selected cases ultrafast CT can contribute to the assessment of severity of calcific aortic stenosis by measurement of LV mass and valve area. PMID- 3344663 TI - Multifocal atrial tachycardia from electrolyte imbalance. PMID- 3344664 TI - Submitral aneurysm diagnosed by left ventricular contrast echocardiography. PMID- 3344665 TI - Two-dimensional echocardiographic imaging of left ventricular mural vegetations. PMID- 3344666 TI - Ruptured aneurysm of sinus of Valsalva: recognition by Doppler color flow mapping. PMID- 3344667 TI - Two-dimensional color Doppler in discrete membranous subaortic stenosis. PMID- 3344668 TI - Systolic antegrade tricuspid blood flow--a sign of severe prosthetic valve stenosis. PMID- 3344669 TI - Metastatic liposarcoma of the right ventricle with outflow tract obstruction: restrictive pathophysiology predicts poor surgical outcome. PMID- 3344670 TI - Urinary thioether biological monitoring in the interaction between 1,2 dichloroethane and disulfiram in Sprague-Dawley rats. AB - The interaction between inhaled 1,2-dichloroethane (ethylene dichloride; EDC) and dietary Disulfiram (tetraethylthiuram disulfide; Antabuse; DSF) was investigated for male Sprague-Dawley rats in terms of urinary levels of thio-compounds extractable in ethyl acetate and then hydrolyzed in alkali (the classic urinary thioether assay). The assay was found to be an inadequate biological monitoring indicator for EDC or DSF exposure during the DSF/EDC interaction at exposures of 0, 153, 304 and 455 ppm EDC (7 hr/day, 5 days/week, 30 exposure days) for rats fed with AIN-76 diet fortified with 0.15% DSF. EDC inhibited the excretion of DSF derived thio-compounds with increasing EDC concentration; the thioether content was dose-related in the absence of DSF. In situations where confounding agents generate neutral S-containing urinary metabolites without involvement of endogenous glutathione, the classic thioether assay requires supplementation by other biochemical monitoring strategies. PMID- 3344671 TI - Radiology, is there an occupational hazard? AB - The practicing radiologist in the United States receives an annual average x-ray dose of 3.2 mSv. This dose of radiation results in between 17 and 28 cancer deaths among the 19,000 radiologists at risk, or an excess cancer risk of between 0.53% and 0.87%. The sub-population of cardiologists and radiologists who perform special procedures is expected to be at a higher risk of death from cancer than the general or therapeutic radiologist. The genetic risk to the children of the radiologist corresponds to a 0.09 to 1.26 excess of cases of genetically determined disease among the 4047 children in the first generation, or between a 0.02% to 0.31% increase above the expected incidence. The progeny of radiologists who have received larger doses in the course of performing cardiac catheterizations or other special procedures are expected to be at a higher risk of expressing a genetically-determined disease than the progeny of the general radiologist. The small size of the population at risk combined with the small magnitude of the risk makes it unlikely that epidemiological studies will be able to demonstrate a statistically significant increased risk of death from cancer or of genetic sequelae in the near future. PMID- 3344672 TI - Chemical protective clothing standard test method development. Part 1. Penetration test method. AB - A "round-robin" interlaboratory study was conducted to validate the relative precision of the American Society for Testing and Materials (ASTM) F-903 test method for measuring the resistance of protective materials to penetration by liquids. The study utilized seven independent laboratories performing three trials of five protective clothing materials challenged by five widely used commercial liquids. The level of overall agreement for interlaboratory results suggests a relatively high confidence in the precision of the method. Systematic errors, however, may reduce the confidence of this method for certain materials and solvents. Recommendations to eliminate or reduce variability due to systematic errors include reduction of test pressure, use of a support screen, reporting of permeation evidence as a failure, and the use of a fluorescent dye to enhance visibility. PMID- 3344674 TI - Occupational noise exposure in the printing industry. AB - The noise exposures of 274 printing production workers in 34 establishments in the New York city area were monitored. Results showed that 43% were exposed to 8 hr time-weighted average (TWA) noise exposures of 85 dBA or greater and that 14% were exposed to 8-hr TWAs of 90 dBA or greater. Within the press department, web press workers were exposed to significantly greater mean 8-hr TWAs than sheetfed press workers. In general, a greater percentage of the workers in the bindery departments were exposed to potentially harmful noise than workers in the press departments. Results of this study indicate that many workers in the printing industry may be at risk of occupational hearing loss. Further research is needed to determine the extent of hearing impairment in this group of workers. PMID- 3344673 TI - Chemical protective clothing standard test method development: Part II. Degradation test method. AB - A "round-robin" interlaboratory evaluation of a proposed American Society for Testing and Materials (ASTM) standard test method was conducted for measuring the resistance of chemical protective clothing materials to degradation by liquid chemicals. The objective of this project was to determine the relative precision of the method and, where appropriate, recommend modifications that would improve reliability. In the round-robin format, eight laboratories used the proposed method to test each of five protective clothing materials against five liquid chemicals that are widely used commercially. The resulting data revealed that the proposed test method was not stringent enough to generate acceptable levels of accuracy and precision. Both intra- and interlaboratory standard deviations showed a high degree of variability in changes for the three physical properties evaluated. Changes in the method were identified which, if implemented, should improve accuracy and precision considerably. PMID- 3344675 TI - The relationship between exposure duration and sulfur dioxide-induced bronchoconstriction in asthmatic subjects. AB - The purpose of this study was to determine the shortest duration of exposure to 1.0 ppm sulfur dioxide (SO2) sufficient to induce bronchoconstriction significantly greater than that observed with exposure to clean air (CA) in exercising SO2-sensitive asthmatics. Asymptomatic, nonmedicated, male asthmatics (n = 12) with airway hyperresponsiveness to both methacholine and SO2 were exposed in a chamber (20 degrees C, 40% relative humidity) for 0.0, 0.5, 1.0, 2.0 and 5.0 min to both CA and 1.0 ppm SO2 on separate days (10 exposures). Just prior to each exposure, subjects walked on a treadmill in CA for 5 min at a predetermined speed/elevation to elicit a target ventilation of about 40 L/min, i.e., a brisk pace up a slight incline. After this walk, subjects rapidly entered an adjoining exposure chamber containing either CA or SO2 and immediately walked at the same speed/elevation for the specified exposure duration. Subjects then rapidly exited the chamber. Specific airway resistance (SRaw) and ratings of respiratory symptoms associated with asthma [shortness of breath/chest discomfort (SB/CD) and wheezing (WHZ)] were measured prior to any exercise and following each exposure. Postexposure SRaw and symptom ratings increased with increased exposure duration in SO2; postexposure SRaw also was increased with increased exposure duration in CA but to a lesser extent. After adjusting for the CA response, significantly greater SO2-induced bronchoconstriction was observed for the 2.0 and 5.0 min exposures as indicated by substantially greater increases in SRaw and substantially higher ratings of respiratory symptoms. The authors conclude that with the above exposure conditions, on average, SO2-sensitive asthmatics exhibit significant bronchoconstriction at exposure durations of 2.0 min or more. PMID- 3344676 TI - Trends in physician management of uncomplicated acute myocardial infarction, 1970 to 1987. AB - To document current management of uncomplicated acute myocardial infarction (AMI), a national survey of 1,065 physicians was performed. Items from previous surveys in 1970 and 1979 were included to permit analysis of time trends in management. Median hospital stay dropped from 21 days in 1970 to 9 days in 1987. Use of beta blockers and aspirin doubled between 1979 and 1987, while use of anticoagulation and sulfinpyrazone dropped 4- to 10-fold. In 1987, coronary angiography was used commonly, especially in younger patients or those with either a non-Q-wave AMI, intravenous thrombolytic therapy or a positive exercise test. These findings document the increasingly aggressive approach to the management of patients with uncomplicated AMI. PMID- 3344677 TI - Factors of importance for prognosis in men with angina pectoris derived from a random population sample. The Multifactor Primary Prevention Trial, Gothenburg, Sweden. AB - A random population sample of middle-aged men from the Primary Prevention Trial was followed for 11.3 years from a first screening when different factors known to be associated with coronary artery disease (CAD) were analyzed. Men with uncomplicated angina pectoris (AP) (n = 167) derived from this population had an incidence of fatal and nonfatal CAD events 3 times higher than that of men without AP or myocardial infarction (n = 5,774). Men with myocardial infarction with or without AP had an incidence of CAD events 7 to 8 times higher than that of men without AP or myocardial infarction. Similar differences were found for new cases of uncomplicated AP (n = 128) and myocardial infarction detected at a second screening after 4 years and followed for 7.3 years. Pooled data from this series of men with uncomplicated AP showed the following factors to be associated in multivariate analysis with nonfatal or fatal CAD endpoints during follow-up: elevated serum cholesterol, elevated blood pressure, smoking and attack score. The risk increase associated with the first 3 factors was similar to the general population. These findings indicate that the same factors affecting prognosis after a first appearance of AP affect similarly patients with myocardial infarction and clinically healthy subjects. Preventive measures against these risk factors seem to be of similar importance among patients with AP, post infarct patients and healthy subjects. PMID- 3344678 TI - Intraaortic balloon pumping for prolonged circulatory support. AB - Prolonged circulatory support with an intraaortic balloon pump (IABP) is controversial, in part because it has not been performed frequently enough to base treatment policy on adequate data. To help clarify this problem, 733 cases of consecutive patients who were supported by IABP between 1967 and 1982 were analyzed. Twenty-seven patients were supported for 20 days or more (range 20 to 71). Twelve (44%) had prior histories of chronic congestive heart failure. Complications were more frequent in prolonged-support patients than in those assisted for less than 20 days (vascular, 37% vs 15%, p = 0.001; infectious, 67% vs 25%, p = 0.0001; and bleeding, 26% vs 15%, p = 0.04, respectively). The survival rate of prolonged-support patients, however, was 63% (17 of 27), essentially the same as that of the controls (57%, p = 0.5). Of 17 prolonged pumping patients discharged alive from the hospital, 9 died within 6 months but 8 survived greater than 2 years. Among congestive heart failure patients, none was a long-term survivor. Prolonged IABP support in congestive heart failure patients lacking surgically correctable lesions can extend life while arrangements for definitive therapy are made (transplant, permanent mechanical assistance). Where definitive therapy is unavailable, IABP may provide additional months of life. PMID- 3344679 TI - Risks associated with intraaortic balloon pumping in patients with and without diabetes mellitus. AB - Between 1967 and 1982, intraaortic balloon pumping (IABP) was attempted in 733 patients. Of these, 132 were diabetic: 51 patients were managed with diet alone, 46 patients took oral hypoglycemic agents and 35 patients required insulin. Vascular complications associated with IABP occurred in 34% of the insulin dependent diabetics, in 18% of other diabetics and in 14% of nondiabetic patients. Infectious complications were 37, 22 and 25%, respectively. Seventy five diabetic patients (57%) were discharged alive from the hospital after balloon pumping, essentially the same proportion as among nondiabetic patients (58%). It is concluded that although diabetics incur a higher complication rate, IABP is not contraindicated. PMID- 3344680 TI - QRS morphology-dependent pharmacodynamics in multiform ventricular ectopic activity. AB - The effect of an infusion of intravenous procainamide on the frequency of ventricular premature complexes (VCPs) of differing QRS morphologies was studied in 20 patients with multiform ectopic activity. In 17 of 20 patients, there was differential suppression of single VPCs with different QRS morphologies. VPCs of the most frequent QRS morphology and the second most frequent QRS morphology were compared with respect to the procainamide level at the escape of VPCs from 85% suppression and the duration of suppression measured from the onset of the procainamide infusion. In 8 patients, VPCs of the most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the second most frequent QRS morphology (escape procainamide concentration = 2.8 +/- 1.7 versus 5.4 +/- 2.3 micrograms/ml, p less than 0.025; time to escape 244 +/- 138 versus 98 +/- 114 min; p less than 0.05). In 9 other patients, VPCs of the second most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the most frequent QRS morphology (escape procainamide concentration 2.9 +/- 1.4 versus 8.3 +/- 6.3 micrograms/ml, p less than 0.025; time to escape 317 +/- 114 versus 63 +/ 80 min; p less than 0.001). Thus, in individual patients there are specific patterns of suppression of VPCs of different QRS morphologies which are independent of the frequency of each morphology. There is apparently a differential pharmacologic effect of procainamide on the foci or pathways responsible for the different QRS morphologies of multiform VPCs. PMID- 3344681 TI - Termination of sustained ventricular tachycardia by external noninvasive pacing. AB - Cardiac pacing has proven useful in the termination of sustained ventricular tachycardia (VT). In this study, the effectiveness of external noninvasive temporary pacing was compared with traditional endocardial burst ventricular pacing for the termination of sustained and hemodynamically stable VT. In 14 patients, 16 VT morphologies induced by programmed right ventricular extrastimulation were reproducibly terminated by endocardial burst pacing (3 to 9 complexes). VT cycle lengths averaged 392 +/- 97 ms (standard deviation) and ranged from 300 to 690 ms. The endocardial burst pacing cycle length used to terminate VT averaged 298 +/- 93 ms (range 220 to 600 ms). External burst pacing terminated 14 of 16 VT morphologies (88%). The pacing cycle length used to terminate these 14 VTs averaged 282 +/- 44 ms. The number of ventricular captures ranged from 5 to 20 beats. Failure to terminate 2 VT morphologies probably represented a failure of the device to capture the ventricle. Acceleration of VT occurred in 1 patient with burst external noninvasive pacing. These observations suggest that external burst pacing may be an effective means of terminating sustained VT in some patients. PMID- 3344682 TI - Prognostic significance of arrhythmia inducibility or noninducibility at initial electrophysiologic study in survivors of cardiac arrest. AB - The value of arrhythmia inducibility or noninducibility at initial electrophysiologic study to predict the likelihood of arrhythmia recurrence was assessed in 150 consecutive survivors of cardiac arrest. Ventricular tachycardia (greater than or equal to 6 beats) or ventricular fibrilation was induced in 113 patients (75%); ventricular arrhythmia could not be induced in 37 patients (25%). During follow-up of a mean of 16 months (range 1 to 72), there were 65 arrhythmia recurrences, 34 of them fatal, in 58 patients. Multivariate regression analysis showed that inducibility at initial study of ventricular tachycardia or ventricular fibrilation was an independent predictor of total arrhythmia recurrence (p less than 0.0001) and fatal arrhythmia recurrence (p = 0.02). At 1 year, 25 +/- 5% of patients with an inducible arrhythmia had a fatal arrhythmia recurrence compared with only 4 +/- 4% of patients without (p = 0.003). The nature of the inducible arrhythmia had no additional predictive value. Inducibility or noninducibility of ventricular arrhythmias at initial electrophysiologic study is a powerful, independent predictor of subsequent arrhythmia recurrence in survivors of cardiac arrest. Patients without inducible arrhythmias have a low frequency of fatal arrhythmia recurrence. PMID- 3344683 TI - Dual balloon technique for valvuloplasty of aortic stenosis in adults. AB - A dual balloon technique was studied in 16 patients with aortic stenosis in whom results with a single balloon (up to 20 mm, 5.5 cm or 25 mm, 3.0 cm in diameter and length, respectively) were judged to be suboptimal. Dual balloon valvuloplasty was performed using 2 balloons advanced and inflated simultaneously across the stenotic aortic valve orifice. For the group as a whole, the average peak transvalvular gradient was reduced from 79 +/- 8 to 57 +/- 7 mm Hg (mean +/- standard error) using a single balloon (p less than 0.0005), and reduced further to 36 +/- 4 mm Hg using dual balloons (p less than 0.0005 compared with single balloon results). Similarly, calculated aortic valve orifice area was increased from 0.45 +/- 0.04 to 0.57 +/- 0.05 cm2 using a single balloon (p less than 0.0005), and further increased to 0.77 +/- 0.06 cm2 using dual balloons (p less than 0.0005). Dual balloon dilation caused no complications directly attributable to the use of 2 balloons, including no exacerbation of aortic regurgitation. These results suggest that dual balloon valvuloplasty is safe and efficacious in selected patients with aortic stenosis. PMID- 3344684 TI - Noninvasive assessment of hemodynamic responses to exercise in pulmonary regurgitation after operations to correct pulmonary outflow obstruction. AB - The influence of pulmonary regurgitation (PR) on exercise capacity is unknown. The hemodynamic responses to exercise in postoperative patients with PR was determined using Doppler-measured regurgitant fraction to indicate PR severity. Maximal heart rate, oxygen consumption and workload capacity were measured during upright cycle ergometry. Cardiac output was measured at rest and during submaximal supine cycle ergometry by pulsed Doppler echocardiography. Oxygen consumption was simultaneously measured and exercise factor was calculated as the change in cardiac output per change in oxygen consumption. Twenty-seven patients were compared with 17 age-, size- and sex-matched control subjects. Patients with PR had larger right ventricles (p less than or equal to 0.001), lower heart rate response (p less than or equal to 0.05), lower maximal oxygen consumption (p less than or equal to 0.005) and lower workloads (p less than or equal to 0.005) when compared with normal control subjects during maximal exercise testing. Exercise factor was the same for both groups. Patients with PR were then separated into mild, moderate and severe groups. Patients with mild PR had a normal response to exercise. However, patients with moderate and severe PR had lower maximal oxygen consumptions and maximal workloads than control subjects. Control, mild and moderate PR groups had similar exercise factors. Patients with severe PR had markedly low cardiac output responses. PR is associated with reduced exercise capability, which is related to the severity of the PR. PMID- 3344685 TI - Effect of iron deficiency on tissue oxygen delivery in cyanotic congenital heart disease. AB - To test the hypothesis that tissue oxygen delivery would be affected by diminished oxygen stores in cyanotic congenital heart disease, serum ferritin, transferrin saturation, hemoglobin, red cell mean corpuscular volume (MCV), red cell 2,3-diphosphoglycerate (DPG), P50, blood gases, oxygen saturations and systemic oxygen transport were measured in 29 hypoxemic infants and children. For the group, aortic saturation was 81 +/- 9%, PaO2 was 50 +/- 12 mm Hg, hemoglobin 16.2 +/- 2.1 gm/dl and systemic oxygen transport 620 +/- 145 ml/min/m2. P50 was increased above normal values (28.8 +/- 2.3 vs 26.6 +/- 1.1 mm Hg, p less than 0.01), and DPG was 2.35 +/- 0.54 mumol/ml, at the upper limits of normal for this assay. Iron deficiency was present in 8. When patients with P50 greater than or equal to 30 mm Hg and P50 less than 30 mm Hg were compared, iron stores were diminished in the high P50 group: [serum ferritin (19 +/- 8 vs 53 +/- 48 ng/ml, p = 0.0006), transferrin saturation (11 +/- 6 vs 23 +/- 11%, p = 0.003) and MCV (79 +/- 8 vs 86 +/- 4 fl, p = 0.05)]. Hemoglobin, aortic oxygen saturation, PaO2 and systemic oxygen transport were similar in both groups. In children with iron sufficiency, 15 of 21 had MCV greater than 90th percentile for age and sex (p less than 0.001 versus expected distribution). Also, MCV greater than 90th percentile for age and sex had a positive predictive value of 0.88 for iron sufficiency. This study demonstrates that diminished iron stores in cyanotic congenital heart disease are associated with a more right-shifted oxyhemoglobin dissociation curve (increased P50).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344686 TI - Surgical risk factors in total anomalous pulmonary venous connection. AB - Eighty-three patients underwent surgical correction of total anomalous pulmonary venous connection (TAPVC) between 1973 and 1986. There were 46 boys and 37 girls. Median age at operation was 60 days (1 to 240) and median weight 3.9 kg (1 to 22). The anatomic types encountered included infracardiac connection (16 patients), supracardiac connection (32) and pulmonary venous drainage connected directly to the coronary sinus (27). Mixed anomalous drainage or pulmonary venous return connected directly to the right atrium occurred in 8 patients. Diagnosis was established by cardiac catheterization and angiography (56 patients), clinical examination (3) and cross-sectional echocardiography alone in 24 of the last consecutive 28 patients. Pulmonary hypertension was present in 26 (55%) of those who underwent cardiac catheterization. The median pulmonary vascular resistance was 4.2 units/m2 (body surface area) for all the patients, whereas in those with infracardiac pulmonary venous connection the median value was 10 units/m2. The median interval between admission and operation was 72 hours. Surgical correction was performed using profound hypothermia and circulatory arrest in 68; for the remainder, conventional cardiopulmonary bypass with profound to moderate hypothermia was used. Ten patients developed 1 or more pulmonary hypertensive crises during the early postoperative period. These were diagnosed in 8 by direct pulmonary artery pressure measurement and in 2 by clinical examination. Late reoperation was necessary in 6 patients (10%). Analyses of risk factors for 30-day survival for all patients showed that the risk of early death was associated with the type of anomaly (infradiaphragmatic), occurrence of pulmonary hypertensive crises, year of the operation, set of the patient and pressure of preoperative congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344687 TI - Accuracy of electrical impedance cardiography for measuring cardiac output in children with congenital heart defects. AB - This study determined whether noninvasive electrical impedance cardiography accurately measures systemic blood flow (cardiac output) in children with congenital heart defects. A total of 37 patients ranging in age from 2 to 171 months underwent complete right- and left-sided heart catheterizations that included simultaneous Fick and impedance measurement of cardiac output. Based on the diagnosis, 4 groups were formed consisting of a control group (n = 11) with no shunts, a group with intracardiac left-to-right shunting and an atrial septal defect (n = 7), another with a ventricular septal defect (n = 12) and an extracardiac left-to-right shunting with patent ductus arteriosus group (n = 7). Impedance values for systemic blood flow were compared with systemic and pulmonary blood flow obtained by the direct Fick method with measured oxygen consumption. The difference between impedance and Fick systemic blood flow was less than or equal to 5% in each of the 4 groups. The highest correlation between impedance and Fick systemic blood flow was with the atrial septal defect group (r = 0.89) and lowest with the ventricular septal defect and control (r = 0.69) groups. Fick pulmonary blood flow was significantly greater than impedance or Fick systemic flow in all 3 shunt groups. Impedance cardiography accurately measured systemic blood flow in children without shunts or valvular insufficiency. Likewise, systemic blood flow was accurately measured by impedance in the presence of intracardiac left-to-right shunts (atrial and ventricular septal defects) and extracardiac left-to-right shunts (patent ductus arteriosus).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344688 TI - Effect of increasing heart rate on left ventricular performance in patients with normal cardiac function. AB - The influence of an increase in heart rate on left ventricular (LV) contractile performance was assessed in patients with normal LV function. In 19 patients (3 men, 16 women) ages 55 +/- 9 years (mean +/- standard deviation) with normal global and segmental LV function and normal coronary arteries, LV dP/dt max was measured at baseline heart rate and during atrial pacing at baseline +5, baseline +25 and baseline +45 beats/min. In 10 of the patients, intravascular volume was not altered during pacing and, as a result, echocardiographically measured LV end diastolic dimension decreased (5.4 +/- 0.4 at baseline vs 4.9 +/- 0.5 cm at baseline +45 beats/min, p less than 0.05). In these patients, LV dP/dt max increased modestly (1,571 +/- 237 at baseline vs 1,760 +/- 199 mm Hg/s at baseline +45 beats/min, p less than 0.05). In the other 9 patients, intravascular volume was expanded rapidly (by saline infusion) during pacing and, as a result, LV end-diastolic dimension was held constant (5.2 +/- 0.6 at baseline vs 5.1 +/- 0.6 cm at baseline +45 beats/min, difference not significant). In these patients, LV dP/dt max increased substantially with pacing (1,505 +/- 228 at baseline vs 2,050 +/- 258 mm Hg/s at baseline +45 beats/min, p less than 0.05). Thus, an increase in heart rate induces a modest increase in LV dP/dt max in patients in whom LV preload (as reflected by end-diastolic dimension) is allowed to decrease; in contrast, it causes a marked increase in LV dP/dt max in those in whom LV preload is maintained constant. PMID- 3344690 TI - Strategies for increasing early adherence to and long-term maintenance of home based exercise training in healthy middle-aged men and women. AB - Two studies were undertaken to compare strategies for the adoption and maintenance of moderate-intensity, home-based exercise training. In the study of adoption, 52 men and women who had served for 6 months as controls for a study of moderate-intensity, home-based exercise training received 30 minutes of baseline instruction. They were then randomized to receive continuing instruction and support through 10 staff-initiated telephone contacts of 5 minutes each every 2 weeks, or to receive no telephone contacts. In subjects receiving telephone contacts, peak oxygen uptake increased significantly after 6 months, whereas no increase was observed in subjects receiving no staff support (p less than 0.05). In the maintenance study, 51 men and women who had significantly increased their peak oxygen uptake by 6 months of moderate-intensity, home-based exercise training were randomized to undergo daily self-monitoring and receive adherence instructions, or undergo weekly self-monitoring only, during a second 6-month period of training. Subjects performing daily self-monitoring reported completing significantly more exercise training sessions during the 6 months of training than subjects performing weekly self-monitoring; functional capacity in both groups remained higher than before training (p less than 0.05). Taken together, these studies suggest that brief baseline instruction followed by continuing telephone contact with staff can be used to help people adopt a moderate intensity, home-based exercise training program that can be maintained by simple self-monitoring strategies. PMID- 3344689 TI - Intrinsic left ventricular contractility in normal subjects. AB - The influence of autonomic tone on left ventricular (LV) contractility, along with the range of normal values and the effects of exercise on contractile state, were studied in 12 normal volunteers. Serial reproducibility was examined in a subgroup of 6. LV contractility was estimated by the LV peak-systolic pressure to end-systolic volume relation (pressure-volume relation), and the ratio of peak systolic pressure to end-systolic volume (pressure/volume ratio). The cuff blood pressure and radionuclide ventriculogram were recorded at rest, during exercise and during pharmacologic pressure-afterloading with phenylephrine, before and after vagal and beta-adrenergic "blockade." Both the pressure/volume ratio and ejection fraction increased during the stimulus of exercise (both p less than or equal to 0.008). After blockade, the pressure-volume relations were highly linear (r = 0.95 +/- 0.05 [standard deviation], n = 12), and there was no systematic difference in their slopes induced by blockade. The serial studies of pressure volume relations showed no significant differences. The results demonstrated that vagal and sympathetic tone were not important in the support of LV contractility in normal subjects at rest, and that the pressure-volume relation and pressure/volume ratio are reproducible between studies. Also, the findings confirmed that both the pressure/volume ratio and the ejection fraction were sensitive to exercise-induced changes in contractility. This demonstration of intrinsic LV contractility in normal subjects, plus the reproducibility of the measurements, supports the feasibility of serial study of LV contractility. PMID- 3344691 TI - Coronary artery disease in women. PMID- 3344692 TI - Primary coronary artery dissection observed at coronary angiography. PMID- 3344693 TI - Allorhythmic preexcitation due to anterograde concealed Kent bundle conduction. PMID- 3344694 TI - Cardiac strangulation: two-dimensional echo recognition of a rare complication of epicardial pacemaker therapy. PMID- 3344695 TI - Incessant pacemaker Vario operation. PMID- 3344696 TI - Modulation of atrioventricular nodal conduction using radiofrequency current. PMID- 3344697 TI - Percutaneous double balloon valvotomy for rheumatic tricuspid stenosis. PMID- 3344698 TI - Clinical features of mitral valve prolapse associated with low body weight. PMID- 3344699 TI - Echocardiographic evaluation of obstructive mechanism of tetralogy of Fallot with restrictive ventricular septal defect. PMID- 3344700 TI - Noninvasive measurement of right ventricular systolic pressure by combined color coded and continuous-wave Doppler ultrasound. PMID- 3344701 TI - United States and Canadian regulation of hypnosis use by psychologists. PMID- 3344702 TI - Not seeing the wood for the trees: implications of susceptibility testing. PMID- 3344703 TI - Hypnosis in the elucidation of hysterical aphonia: a case report. PMID- 3344704 TI - Use of hypnotic imagery for self-diagnosis. PMID- 3344705 TI - Ethics committees. PMID- 3344707 TI - Lead poisoning and public policy. PMID- 3344706 TI - The legal imperative and the meconium-stained newborn. PMID- 3344708 TI - Unusual multiply resistant pneumococci. PMID- 3344709 TI - Candidal suppurative thrombophlebitis in a premature infant. PMID- 3344710 TI - Reversible true precocious puberty secondary to a congenital arachnoid cyst. PMID- 3344712 TI - Aids, children and primary care physicians. PMID- 3344711 TI - Hypercalciuria in the premature infant: influence of diuretic therapy and phosphate depletion. PMID- 3344713 TI - Extracorporeal shock-wave lithotripsy for children. AB - We report the cases of 17 children between the ages of 3 and 17 years who underwent 19 treatments using extracorporeal shock-wave lithotripsy. Stone size averaged 14.9 mm, with a range of 3 to 25 mm. The number of shock waves delivered averaged 1720, with a range of 600 to 2000. Treatment time averaged 36 minutes, with a range of 15 to 55 minutes. The average length of hospital stay was 2.2 days. In nine of the 19 treatments the kidneys were rendered free of stones. There were no complications. PMID- 3344714 TI - Influence of parental knowledge and opinions on 12-month diphtheria, tetanus, and pertussis vaccination rates. AB - To assess the magnitude and cause of decreasing diphtheria, tetanus toxoids, and pertussis (DTP) immunization rates, a retrospective cohort study investigated the immunization status against pertussis among 1-year-old children in Utah. Questionnaires were sent to the parents of 2975 children born in June 1985. Parents were asked about each child's DTP immunization status, including the number, type, and dates of the vaccinations, reasons for or against vaccination, and their knowledge of whooping cough and the vaccine. Children were considered adequately immunized against pertussis when they had received three DTP vaccinations by their first birthday. In Utah, the lack of pertussis immunization among young children is a serious problem: greater than 30% of 1-year-old children were not adequately protected. Accurate parental knowledge about the relative risks of vaccination and illness was associated with a greater likelihood for immunization. Although some parents chose to forego the vaccination because they were concerned about its side effects, the most common reason for incomplete immunization was illness at the time the vaccination was to be given. If immunization rates are to improve, health care professionals must not only make an effort to educate the general population regarding the vaccine, but they must also ensure immediate follow-up for immunization when the procedure is delayed. PMID- 3344715 TI - A prospective evaluation of iron chelation therapy in children with severe beta thalassemia. A six-year study. AB - Sixteen patients (age range, 3 to 17 years) with transfusion-dependent beta thalassemia major were studied prospectively, beginning at the onset of chelation therapy with deferoxamine (desferrioxamine). A liver biopsy specimen was obtained from each patient at the start of the study, and periodically thereafter. Liver histologic features, iron content, and iron excretion were assessed during the course of the study. Hepatic iron levels from liver biopsy specimens appeared to correlate well with serum ferritin levels in the younger less heavily iron-loaded patients; however, in patients with higher serum ferritin levels, hepatic iron appeared to reach a saturation level. Fourteen of the 16 patients showed a pattern of marbled fibrosis of the liver in their initial biopsy specimens. Follow-up biopsy specimens from nearly all of the patients showed a substantial reduction in iron concentration, but only two of seven patients showed improvement in the degree of hepatic fibrosis three to five years later. Patients less than 8 years old exhibited a normal pattern of linear growth until approximately the age of 10 years, followed by a progressive decrease to the 30th to 40th percentile. Two patients, aged 18 and 22 years, died of cardiac disease during the study. These findings suggest that chelation therapy in patients with transfusion-dependent thalassemia needs to be initiated at an early age, possibly before 3 years, if significant liver fibrosis and growth impairment are to be effectively prevented. PMID- 3344716 TI - Outcome of persistent pulmonary hypertension in relation to severity of presentation. AB - Since the initial description of persistent pulmonary hypertension of the newborn (PPHN), the management of these infants has been controversial. A variety of therapeutic modalities, such as extracorporeal membrane oxygenation, have been utilized. Early recognition of a group of patients with PPHN who might require aggressive therapy would be clinically useful. Highest alveolar-arterial oxygen gradient at or near diagnosis was evaluated retrospectively in 53 patients with PPHN in relation to survival, aggressiveness of management, and frequency of pulmonary complications (air leak and broncho-pulmonary dysplasia). Highest alveolar-arterial oxygen gradient was a good early predictor of nonsurvival and was significantly higher in nonsurvivors compared with survivors (mean [+/- SD], 618 +/- 23 mm Hg vs 521 +/- 128 mm Hg). Values of 600 mm Hg or greater were more frequent in the nonsurvivors compared with the survivors (92% vs 37%). Air leak also proved to be a good predictor of nonsurvival. PMID- 3344717 TI - Variable expression in focal dermal hypoplasia. An example of differential X chromosome inactivation. AB - We encountered three women from three generations of the same family with features of focal dermal hypoplasia (FDH). Two of the patients, the proposita and her mother, demonstrated severe manifestations, including skin, dental, skeletal, and visceral abnormalities. The proposita's grandmother, the first family member affected, had very mild expression, with aplasia cutis congenita and dental caries as the only features expressed. This family illustrates both the marked variability of expression and the proposed X-linked dominant mode of inheritance of FDH. We postulate that early embryologic random inactivation of the X chromosome bearing the mutant gene responsible for FDH is the cause of the variable expression. PMID- 3344718 TI - Radiological case of the month. Dyke-Davidoff-Masson syndrome. PMID- 3344719 TI - Picture of the month. Cutis verticis gyrata. PMID- 3344720 TI - Cryptosporidium, malnutrition, and chronic diarrhea in children. AB - Cryptosporidium was found in the stools of 13.5% of 221 children hospitalized with diarrhea. It was the single most prevalent pathogen isolated. Children with Cryptosporidium-positive stools were significantly more malnourished than children in whom Cryptosporidium was not detected. Children with more severe malnutrition (ie, less than 50% of their expected weight) and with Cryptosporidium in their stools had a significantly longer duration of diarrhea than similarly malnourished children without Cryptosporidium (63 vs 32 days, respectively). In 77 better-nourished outpatients with diarrhea, Cryptosporidium was found in only 5.2% of cases and was associated with less-severe illness. Our findings are consistent with the hypothesis that in less-developed areas, Cryptosporidium is a major pathogen, not only in acute but also in chronic childhood diarrhea, and may play an important role in the interaction between diarrhea and malnutrition. PMID- 3344721 TI - Amaurosis fugax in teenagers. A migraine variant. AB - Sudden, transient loss of vision in one eye (amaurosis fugax) is associated frequently with atherosclerosis of the internal carotid artery in adults and may herald a stroke. Thus, cerebral angiography is often performed. Amaurosis fugax in children is uncommon and an underlying cause is rarely demonstrated. Recurrent episodes of amaurosis fugax occurred in five adolescents. A characteristic evolution and pattern of visual loss, consistent with choroidal ischemia as the underlying mechanism, was described by four of them. Although none of the episodes were accompanied by headache, four patients had a history of common migraine at other times or a family history of migraine. These episodes of visual loss may represent a migraine variant, and cerebral angiography is not indicated in adolescents with such a history. PMID- 3344722 TI - Factors associated with infantile hypertrophic pyloric stenosis. AB - We examined perinatal factors in relation to the rise in incidence of infantile hypertrophic pyloric stenosis among children in Olmsted County, Minnesota, during the period from 1950 through 1984. Primogeniture was associated with male infants but not female infants; some factor related to primogeniture, such as breast feeding, may be etiologically important. Our data did not support a role for maternal disease, use of doxylamine succinate-pyridoxide hydrochloride (Bendectin), or an infectious process. Further study should be directed toward environmental factors associated with primogeniture. PMID- 3344723 TI - The cause of rectal prolapse in children. AB - Fifty-four pediatric patients with rectal prolapse (RP) were identified by review of medical records from 1977 to 1987. Rectal prolapse was attributed to chronic constipation (15 patients), acute diarrheal disease (11 patients), cystic fibrosis (CF) (six patients), and neurologic/anatomic abnormalities (13 patients). In nine patients, no underlying cause was identified. The patients with CF did not differ from the other groups in terms of age at time of onset of prolapse, growth measurements, or number of episodes of prolapse. All patients with CF had a history of abnormalities or presented with signs and symptoms consistent with this diagnosis; none had a history of constipation. Although physicians can be reassured that CF is not a likely diagnosis in patients with RP and acute diarrheal disease or a clear history of constipation, a sweat test is indicated in all such cases as well as in those in which there is no apparent underlying cause. A sweat test is not usually indicated in patients with RP in association with underlying anatomic abnormalities. PMID- 3344724 TI - Polyethylene glycol-electrolyte solution for intestinal clearance in children with refractory encopresis. A safe and effective therapeutic program. AB - Severely constipated children with encopresis in whom outpatient management has failed frequently require several days of hospitalization, as well as conventional treatments involving cathartics and enemas. A balanced electrolyte solution of the nonabsorbable polymer polyethylene glycol (GoLytely, Braintree [Mass] Laboratories Inc) offers a safe and efficient method for clearing the intestine. Twenty-four patients with a mean age of 8.1 years (range, 0.8 to 17.6 years) and an average weight of 31.5 kg received polyethylene glycol-electrolyte solution: eight patients with encopresis were given it as treatment for severe fecal retention unresponsive to outpatient management; the other 16 were being prepared for colonoscopy. Weight, complete blood cell count, and serum electrolyte, serum urea nitrogen, and serum creatinine levels were measured before solution administration and two hours afterward. Abdominal roentgenograms were obtained from the encopretic patients. The two groups were comparable in age and weight. Polyethylene glycol-electrolyte solution was given at a rate of 14 to 40 mL/kg/h until clear fluid was excreted through the rectum. Intestines were cleaned out successfully in all patients, and side effects were minimal. Children with encopresis required an average of 11.8 L (574 mL/kg) given over 22.5 hours, while the other children needed only 4.0 L (128 mL/kg) given over 7.5 hours. Weight and serum electrolyte and creatinine levels did not change significantly in any patient. The hematocrit decreased only in encopretic patients (0.38 to 0.36 [37.6% to 35.8%]) and the serum urea nitrogen level decreased in the patients undergoing colonoscopy (3.6 to 2.0 mmol/L [10 to 8 mg/dL]). PMID- 3344725 TI - Muscle atrophy and leg length discrepancies in pauciarticular juvenile rheumatoid arthritis. AB - In 32 children with pauciarticular juvenile rheumatoid arthritis, we studied residual muscle atrophy and leg length discrepancy after the arthritis had entered remission. Children under the age of 3 years at disease onset had significantly more muscle atrophy and bone overgrowth than children whose disease began after the age of 3 years. These residua have cosmetic and functional significance, and new methods of treatment will be necessary to prevent or reverse the sequelae in a form of arthritis previously thought to have a benign outcome. PMID- 3344726 TI - Clinical trials in ulcerative colitis: I. Personal observations. PMID- 3344727 TI - Venous, arterial, and arterialized-venous blood ammonia levels and their relationship to hepatic encephalopathy after propranolol. AB - To assess side effects of propranolol in the treatment of portal hypertension, we measured blood ammonia in 14 cirrhotics before and after administration of propranolol, and in six cirrhotics before and after placebo. We evaluated ammonia blood levels obtained from three sites: venous, arterial, and arterialized venous, obtained by warming the forearm. Ammonia concentration of arterial and arterialized-venous blood were abnormal for all cirrhotics studied and significantly greater than the ammonia concentration of venous blood (p less than 0.01). When propranolol was administered to patients with alcoholic cirrhosis and marginal liver function, as reflected by ammonia levels above 60 microM, it caused a significant increase in ammonia levels in arterialized-venous and arterial, but not in venous, blood (p less than 0.05). Propranolol caused a significant increase in the time required to perform sensitive psychometric tests (p less than 0.05). Encephalopathy usually became clinically apparent when the mean of the arterial and arterialized-venous blood ammonia levels rose above 122 microM. PMID- 3344728 TI - Hepatic inflammation, hepatitis B replication, and cellular immune function in homosexual males with chronic hepatitis B and antibody to human immunodeficiency virus. AB - We measured serum aspartate transaminase (AST) concentration and serum hepatitis B virus (HBV) DNA concentration in homosexual men with chronic HBV infection and a spectrum of immune deficiency as a result of exposure to human immunodeficiency virus (HIV). Serum AST and HBV DNA concentrations were similar in patients with varying immune function as indicated by in vivo criteria (diagnosis and skin tests reactivity) and in vitro criteria (lymphocyte transformation responses to mitogens and Candida and tetanus antigens) and were unrelated to the number of circulating T cells, suppressor/cytotoxic cells, helper cells, natural killer cells, and the helper:suppressor ratio. Serum AST concentration and indices of cellular immune function were similar in patients with varying HBV replicative activity (high and low HBV DNA concentrations). The observed lack of relationship between serum AST concentration and indices of cellular immune function and HBV replication suggests either that other factors determine the severity of hepatic inflammation in chronic HBV infection, or that currently available tests of cellular immune function and HBV replicative activity do not accurately reflect processes in the liver. PMID- 3344729 TI - Colonic neoplasms in asymptomatic first-degree relatives of colon cancer patients. AB - First-degree relatives of colon cancer patients are at elevated risk for developing colorectal neoplasms. In order to assess the potential usefulness of screening by colonoscopy in this high-risk population, we reviewed the records of 48 colonoscopies performed on asymptomatic patients who were self- or physician referred for colonoscopy because of a history of one or more first-degree relatives with colon cancer. Twelve (25%) had at least one adenomatous polyp, but no significant atypia was detected. No cancers were detected. One third of the lesions were beyond the reach of a flexible sigmoidoscope. This apparent increase in the prevalence of adenomas was most striking (46%) among men over the age of 50. These preliminary results demonstrate that colonoscopy is effective in detecting and removing adenomatous polyps in a substantial fraction of asymptomatic patients whose sole risk-factor is being a first-degree relative of a patient with colon cancer. Further studies in larger populations are warranted to determine the use of colonoscopy in screening these high-risk individuals. PMID- 3344730 TI - Histological gastritis in duodenal ulcer: relationship to Campylobacter pylori and effect of ulcer therapy. AB - Antral gastritis has been described in up to 100% of patients with duodenal ulcer disease, and recently has been associated with Campylobacter pylori infection. The present study examines the effect of two ulcer therapies (cimetidine and colloidal bismuth subcitrate) on this lesion. Sixty-four consecutive patients with endoscopically diagnosed duodenal ulcer were randomized to treatment with either agent upon entry into the study. Antral biopsies were taken at both initial and final endoscopies for culture of C. pylori and assessment of degree of gastritis (as based on inflammatory cell infiltrate: grades 0 to 3). The organism was detected in 90% of the patients at initial biopsy, and grades 2 and 3 gastritis were documented in 76%. The presence of the organism and the gastritis were significantly correlated (p less than 0.001), and the bacterium was not cultured from histologically normal antral mucosa. Active chronic gastritis (grade 3) was seen in 65% of those with C. pylori, and was not found in any patient without the bacterium. Cimetidine had no effect on either the organism or the gastritis, whereas the bismuth preparation significantly (p less than 0.002) reduced the prevalence of both. The present study documents that therapy directed against C. pylori has a significant effect on the gastritis of duodenal ulcer disease and possible mechanisms for the observed effects are discussed. PMID- 3344731 TI - Validation of an ambulatory esophageal pH monitoring system. AB - The present study documents the accuracy of a commercially available ambulatory esophageal pH instrument. The distal esophagus of five subjects with daily heartburn was monitored for 24 h in the laboratory via an antimony pH electrode. The computer output from the ambulatory unit was compared to the on-line recording in terms of all events in which the pH dropped below four. A signal detection model was used, with an on-line pH tracing serving as the criterion response. The events noted as true positives (80%) were an accurate representation by the computer output of the events of pH less than four displayed by the on-line recording. The processing done by this particular ambulatory system tends to actually "ignore" transient pH drops (18% false negatives) and, may, in fact, provide more physiologically meaningful information than hardwired analog techniques for 24-h pH monitoring. The results confirm that ambulatory pH monitoring can produce meaningful and reliable physiological data concerning gastroesophageal reflux. PMID- 3344732 TI - Tetanus after gastrointestinal surgery. AB - Tetanus, which occurs usually as a complication of minor trauma, has also been reported following elective and emergency surgical procedures, particularly those involving the gastrointestinal tract. Early diagnosis of tetanus in the postoperative period is difficult, requiring a high index of suspicion. The possibility of tetanus should be considered in any nonimmunized postoperative patient who develops crampy abdominal pain, fever, and abdominal wall rigidity. Adequate tetanus immunoprophylaxis is essential for all patients undergoing gastrointestinal surgery. PMID- 3344734 TI - Absence of diarrhea in toxic megacolon complicating Clostridium difficile pseudomembranous colitis. AB - We describe a patient with Clostridium difficile-associated pseudomembranous colitis who presented with toxic megacolon without diarrhea. The discussion includes a brief review of the literature, and suggests an important role for endoscopy in the diagnosis of pseudomembranous colitis and, possibly, as part of the therapy for toxic megacolon associated with Clostridium difficile colitis. The unusual combination of toxic megacolon without antecedent diarrhea should be recognized as a possible manifestation of antibiotic-associated pseudomembranous colitis, especially in the setting of simultaneous antimicrobial and opiate administration. Early diagnosis and disease-specific intervention can be lifesaving. PMID- 3344733 TI - Lymphadenopathy in celiac disease: not always a sign of lymphoma. AB - A patient with celiac disease and mesenteric adenopathy discovered on computerized scanning of the abdomen is described. Lymphadenopathy resolved more than 6 months after the institution of a gluten-free diet. Adenopathy without evidence of lymphoma may be part of the clinical manifestations of patients with celiac disease. Follow-up with computerized tomography may be an option in patients with low clinical suspicion for lymphoma. PMID- 3344735 TI - Primary sclerosing cholangitis: symptomatic and cholangiographic improvement after peripheral drainage. AB - Presented is a patient with primary sclerosing cholangitis, extrahepatic bile duct obstruction, and associated occlusion of the main portal vein, who was treated by peripheral biliary drainage. Radiological follow-up showed considerable improvement of the ductal strictures and bile excretion through the normal anatomical route. The patient remains well and anicteric 60 months after surgery. PMID- 3344736 TI - Veno-occlusive disease of the liver in a patient with allergic granulomatous angiitis. AB - A 45-yr-old woman, with asthma and skin erythema, was diagnosed as having allergic granulomatous angiitis. Leukocytosis accompanied by hypereosinophilia and characteristic histological findings of skin lesions also were present. Upon laparoscopy and liver biopsy, the liver showed a congestive appearance and, histologically, showed thickening of the central vein walls, as well as narrowing of the lumens with collagenous fibers, and pericentral hemorrhage with hepatocyte degeneration. A diagnosis of veno-occlusive disease of the liver was made. This is the first report on a case of veno-occlusive disease of the liver occurring in association with allergic granulomatous angiitis. PMID- 3344737 TI - Intrahepatic lymphocyte subpopulations in acute hepatitis in an adult with rubella. AB - Rubella accompanied by serum aminotransferase elevations occurred in a 24-yr-old man. Liver biopsy showed ballooning degeneration and focal necrosis of liver cells, clumped Kupffer cells, and infiltration of inflammatory cells, mainly of the mononuclear type. Most mononuclear cells in the liver were CD8-positive and CD16-negative cells (cytotoxic T cells) which were in broad contact with the surface of liver cells. Leu 7 (natural killer) cells were few and sporadic. HLA class I antigens were expressed on liver cell membrane. Although hepatic involvement in adult rubella is not generally recognized, it may have been the cause of this patient's liver injury. Thus, cytotoxic T cells may play a role in liver injury in acute rubella infections in adults. PMID- 3344739 TI - Hepatic portal venous gas due to endoscopic sphincterotomy. AB - This report describes a patient with sickle cell disease and cholelithiasis with choledocholithiasis who developed benign hepatic portal venous gas following endoscopic sphincterotomy. The portal venous gas was rapidly absorbed without untoward sequelae. PMID- 3344738 TI - Chlamydia trachomatis perihepatitis with ascites. AB - Chlamydia trachomatis as an etiological agent in the Fitz-Hugh-Curtis syndrome has recently been reported; however, the condition has not been typically associated with ascites. We report a case of Chlamydia trachomatis perihepatitis in a young woman who had exudative ascites as a predominant clinical feature of her disease. Laparoscopy revealed characteristic "violin string" adhesions which were also identified on abdominal computerized tomographic scan. PMID- 3344741 TI - Ranitidine-induced bradycardia. PMID- 3344740 TI - Diagnosis of nontraumatic hematobilia by computerized tomography of the abdomen. AB - Hematobilia was diagnosed by computerized tomography as the cause of gastrointestinal bleeding in a 73-yr-old man. The patient suffered from recurrent abdominal pain for 4 yr and presented with a history of episodic hematochezia over the previous 24 h, suggestive of significant lower gastrointestinal bleeding. Endoscopic evaluation of the lower and upper gastrointestinal tract revealed only blood in the region of a normal ampulla. Computerized tomography demonstrated a thickened gallbladder filled with material the density of blood. A blood-filled gallbladder was removed at cholecystectomy and pathological examination of the excised gallbladder demonstrated ulceration and inflammation of the mucosa. The diagnostic evaluation of hematobilia is discussed. PMID- 3344742 TI - Massive hepatic hydrothorax without ascites: the complexities and "costs" of management. PMID- 3344743 TI - The long-term outcome of hepatitis B infection in hemodialysis patients. AB - Little information on the long-term outcome of hepatitis B virus (HBV) infection in hemodialysis patients is available. We studied 49 hemodialysis patients, seen at three centers between 1969 and 1985, who developed HBV infection. Patients were studied retrospectively and followed for up to 10 years (mean 52 +/- 5 months). Only 20% (n = 10) of patients converted to hepatitis B surface antigen (HBsAg) negative, the majority of whom did so within 6 months of becoming HBsAg positive. Twenty-nine percent (n = 14) of patients developed chronic elevation of liver enzymes which remitted in one patient. Only one patient died from liver disease. We conclude that HBV infection in hemodialysis patients more often results in persistent antigenemia and chronic elevation of liver enzymes than is the case in patients without kidney disease. However, the risk of death from liver disease is low. PMID- 3344744 TI - Nitrogen losses and cephalothin absorption in peritonitis treated by hourly peritoneal dialysis. AB - The effects of peritonitis on dialysate nitrogen losses were investigated. Eight patients who developed peritonitis while undergoing peritoneal dialysis were compared to seven noninfected dialysis patients. Dialysate protein losses increased during peritonitis, but nitrogen losses into the dialysate did not increase. These findings were caused by reduced urea nitrogen losses in the peritonitis group, which proportionately, more than made up for the increased nitrogen losses from protein. We speculate that the smaller loss of urea nitrogen was due to diminished intake of food. Cephalothin uptake from the peritoneal cavity was unaltered by peritonitis and a dialysate flow rate of 2 L/hour averaged 26 +/- 2 mL/minute and 27 +/- 2 mL/minute in the noninfected and infected groups, respectively. PMID- 3344745 TI - The plasma potassium concentration in metabolic acidosis: a re-evaluation. AB - The purpose of these investigations was to describe the mechanisms responsible for the change in the plasma [K] during the development and maintenance of hyperchloremic metabolic acidosis. Acute metabolic acidosis produced by HCI infusion resulted in a prompt rise in the plasma [K], whereas no change was observed during acute respiratory acidosis in the dog. After 3 to 5 days of acidosis due to NH4Cl feeding, dogs became hypokalemic; this fall in the plasma [K] was due largely to increased urine K excretion. Despite hypokalemia, aldosterone levels were not low, and the calculated transtubular [K] gradient was relatively high, suggesting renal aldosterone action. Thus, rather than anticipating hyperkalemia in patients with chronic metabolic acidosis due to a HCl load, the finding of hyperkalemia should suggest that the rate of urinary K excretion is lower than expected (ie, there are low aldosterone levels or failure of the kidney to respond to this hormone). PMID- 3344746 TI - Radionuclide exploration of dialysis amyloidosis: preliminary experience. AB - The noninvasive diagnosis of amyloid arthropathy in dialysis patients is still uncertain. Therefore, we investigated the potential diagnostic value of the 99mTc methylene diphosphonate scan in seven long-term hemodialysis patients suffering from chronic joint pain who had biopsy-proven osteoarticular amyloidosis of the recently discovered beta 2-microglobulin (beta 2-M) type. In six, but in none of five control patients on short-term hemodialysis, increased tracer uptake was found at the site of one or several articular and/or periarticular regions. Increased uptake at a given joint was often, but not always, associated with joint pain. It appeared to precede radiologically visible changes. In conclusion, the 99mTc-methylene diphosphonate scan may be of help in the early diagnosis of dialysis amyloidosis. PMID- 3344747 TI - A clinical index to predict survival in acute renal failure patients requiring dialysis. AB - Recent advances in technology have not substantially changed the relatively low survival rate associated with acute renal failure (ARF). Several clinical prognostic variables and multivariate models have been reported to predict survival in individual patients, but these are either cumbersome to use or restrictive in their application. A straightforward clinical index has been developed to predict survival in ARF based on data obtained for all patients receiving dialysis for ARF at the University of Kansas Medical Center from November 1979 through October 1985. During this period, 126 patients received dialysis for ARF, with an overall survival of 25% (32/126). There were no significant differences between survivors and nonsurvivors in age, gender, or indication for dialysis. Eleven variables were statistically related to survival, and were reduced to five when clinically similar variables were combined or eliminated. A clinical survival index was based on these five easily determined variables that were significantly related to survival: systolic blood pressure less than or equal to 110 mm Hg, assisted ventilation, congestive heart failure, proven or suspected sepsis, and gastrointestinal (GI) dysfunction (bleeding, ileus, obstruction, or recent abdominal surgery). Survival was directly related to the number of factors present: zero, 62% (8/13); one, 44% (8/18); two, 30% (10/33); three, 19% (5/26); four, 0% (0/20); and five, 6% (1/16). This straightforward index, derived from easily obtained clinical data, is useful for judging survival prognosis in patients with ARF severe enough to warrant treatment with dialysis. PMID- 3344748 TI - Ethylene glycol intoxication. PMID- 3344749 TI - Smoking and occupation in epidemiologic studies. A workshop sponsored by the National Cancer Institute and the National Institute for Occupational Safety and Health. Bethesda, Maryland, December 15-16, 1986. PMID- 3344750 TI - Indirect methods of assessing the effects of tobacco use in occupational studies. AB - For various reasons, data on smoking are frequently missing, or only partially available, in retrospective epidemiologic studies of occupational risk factors. In such situations, indirect methods may be used to evaluate the magnitude and direction of the potentially confounding effects of smoking. Such an evaluation can be made quantitatively or qualitatively. Here we describe both approaches. A specific problem relates to case-referent studies, where sampling variation in referent selection may limit the possibility of controlling for confounding by smoking, even when smoking data are available. We present data showing that estimates of risk from occupational exposures which are not controlled for smoking may be as accurate as estimates derived after controlling for smoking, when the number of referents is relatively small. The problem of interaction is also discussed. In the absence of smoking data, the investigator has no indication of how smoking and occupation jointly affect disease risk (eg, additively or multiplicatively). The multiplicative model is usually assumed. However, if exposure and smoking act independently (additively), rate ratios are diminished. In such situations, in the presence of negative confounding by smoking, rate ratios may actually even be less than one--also when exposure and disease are strongly related. PMID- 3344751 TI - Indirect corrections for confounding under multiplicative and additive risk models. AB - We define a multiplicative model and an additive model for the hazards associated jointly with exposure and with the presence of a confounder like smoking. Under the multiplicative model, the crude relative risk may be adjusted indirectly, by means of a factor proposed by Axelson [1978], and implicitly by Cornfield et al. [1959] and Schlesselman [1978]. We present corresponding indirect correction formulas under the additive risk model for the risk difference and for the excess relative risk. Conditions are established under which these corrections may be applied to age-adjusted rates from composite study populations. We demonstrate that indirect corrections may be no better than crude measures of risk if one assumes the wrong model for the joint action of the exposure and confounding factors. These results are illustrated on an example of occupational exposure to vermiculite. The limitations of the techniques are discussed. PMID- 3344752 TI - Methods for testing interactions, with applications to occupational exposures, smoking, and lung cancer. AB - Various approaches to assessing the interaction between smoking and occupational exposures are described. The definition of interaction depends on the measure of association under consideration and can be expressed in terms of disease risk, time, or dose. Simple descriptive methods and maximum likelihood model fitting methods are presented for analyzing interactions in terms of joint effects on disease risk. Methods for assessing the influence of exposures on times to disease, using appropriate denominators, are also described. The various approaches are illustrated with published data on lung cancer in relation to asbestos, radon daughters, chloromethyl ethers, and arsenic. Some of the mechanisms that can be invoked to explain the observed patterns include initiation and promotion, lung clearance, transport across cell membranes, and mucous secretion. PMID- 3344754 TI - Control of smoking in occupational epidemiologic studies: methods and needs. PMID- 3344753 TI - Relative risk models for assessing the joint effects of multiple factors. AB - A goal of analyses of occupational cohort data is the specification of how covariate information relates to age-specific disease risks. In describing this relationship, certain assumptions or models must be defined. For example, the usual standardized mortality ratio assumes a constant multiplicative increase in the age and calendar period disease rates of an exposed cohort over rates in a unexposed referent group. For analyzing several exposures, some of which may be continuous, such as cumulative dose, dose rate, duration of employment, and smoking patterns, or for analyzing complex associations between disease rate and covariates, flexible regression procedures are required. Using a crossclassification of the data and a Poisson probability model, relative risk regression methods are outlined. Breslow and Storer [1985], Guerrero and Johnson [1982], and Thomas [1981] propose general models for the relative risk as alternatives to, but which include, the usual exponential form. We review these models, discuss some limitations (in particular when there is more than one covariate) and present alternatives. Methods and models are illustrated by examining the joint effects of radon exposure and tobacco use on lung cancer mortality among a group of uranium miners. PMID- 3344755 TI - Smoking characteristics of US workers, 1978-1980. AB - Data from the 1978-1980 National Health Interview Survey smoking questionnaire were used to analyze prevalence and levels of cigarette smoking among groups of US workers. This information is valuable for indirect adjustment in occupational epidemiology studies as well as for describing smoking patterns of workers in a wide range of job settings. Although there was a higher percentage of current smokers among men than women in the general population, there were few differences in prevalence of smoking among men and women for specific occupations. Also, race and employment status had an influence on prevalence of smoking, where both the currently unemployed and blacks generally had a higher proportion of current smokers, although blacks generally had a higher proportion of current smokers, although blacks smoked fewer cigarettes. Industry also played a major role in the variation of smoking habits. For instance, the percentage of current smokers of a given occupation had as much as a 25% difference depending on the industry they were employed, such as 52% vs 26% for managers and administrators. Detailed data will be made available as microcomputer files for interested researchers. PMID- 3344756 TI - Smoking and degree of occupational exposure: are internal analyses in cohort studies likely to be confounded by smoking status? AB - Occupational cohort studies are usually carried out without the benefit of information on smoking habits of cohort members. One common approach to avoid confounding bias related to smoking habits is to carry out an internal analysis, comparing workers with different degrees of occupational exposure. The premise behind this approach is that within a cohort there is unlikely to be correlation between degree of exposure and smoking habits. If this were untrue, smoking could confound the disease-exposure relationships. Our purpose was to verify the premise. The study sample consisted of 857 French-Canadian men born between 1910 and 1930, with 11 or fewer years of education, and interviewed around 1980 in the context of an occupational cancer case-control study. For each man we had information on smoking habits, job history, and a history of the chemicals he was exposed to in each of his jobs. We computed two indices of the dirtiness of workers' job histories: one based on the job titles held by the man and a second based on the degree of exposures to workplace substances. There was no correlation between these indices of job dirtiness and smoking history. We also examined the smoking-exposure relationship among the subsets of men who had been occupationally exposed to ten especially noticeable substances. Within the subsets, there was no indication of a consistent difference among the smoking subgroups in level or duration of exposure to these index substances. These findings do not support the view that nonsmokers sought out cleaner job environments than smokers; they imply that internal analyses of "dose-response" in cohort studies are unlikely to be seriously confounded by smoking habits. PMID- 3344757 TI - Gallbladder dynamics and plasma cholecystokinin responses after meals, oral water, or sham feeding in healthy subjects. AB - To investigate the mechanisms controlling human gallbladder contraction, especially to determine the role of neural factors, the gallbladder response to various stimuli was evaluated in eight normal subjects using realtime ultrasonography. In addition, plasma cholecystokinin (CCK) levels were measured using a region-specific antibody (OAL 656). Intramuscular injections of CCK-8 and of cerulein induced mean maximal ejection fractions (EF max) of 50% +/- 6% and 58% +/- 4%, respectively. The mean EF max after ingestion of a fatty meal was 44% +/- 3%, while the EF max after a fat-restricted meal was significantly lower (17% +/- 4%). Oral water and sham feeding also significantly induced gallbladder contractions (EF max; 25% +/- 4% and 12% +/- 4% respectively) that were eliminated by premedication with atropine. The plasma CCK rose significantly after exogenous administration of CCK-8 and after ingestion of a fatty meal. The peak CCK concentration released after fatty meals was almost identical to that after exogenous CCK-8 loading. In contrast, plasma CCK levels showed no change after the fat-restricted meal, oral water and sham feeding. These findings suggest that not only CCK but also the cholinergic pathway may play important roles in the control mechanism of human gallbladder contraction. PMID- 3344758 TI - Enhancement of peritoneal transport in rats by disrupting stagnant fluid films. AB - Dialysate comes into contact with the active membrane and remains in contact until the fluid is refreshed. This design exaggerates stagnant fluid films. Dialysis rate studies were done to evaluate transport when stagnant fluid films were disrupted. Following anesthesia, 30 mL of commercial 1.5% glucose dialysate containing 100 mg% urea and 25 mg% inulin warmed to 37.5 C were instilled. Dialysate was sampled at 5, 15, 30, 45, and 60 min after instillation. Experimental rats were vibrated at 25 Hz throughout the study. Diffusive mass transfer coefficients (MTC mL/min 1000 cm2) were calculated, and control and vibrated group means were tested for differences using Student's t-test. The mean MTC values for control (n = 10) and vibrated groups (n = 12), respectively, were: urea 0.8 +/- 0.04, 1.4 +/- 0.2, p less than 0.01; glucose 0.4 +/- 0.03, 0.6 +/- 0.03, p less than 0.01; insulin 0.2 +/- 0.01, 0.2 +/- 0.01, p = NS. Disrupting stagnant fluid films augments peritoneal transport. PMID- 3344759 TI - Infectious mononucleosis in hospitalized patients over forty years of age. AB - Clinical and laboratory features of 17 patients over 40 years of age (mean age: 55 years) admitted with infectious mononucleosis were compared with those of 17 adolescents (mean age: 13 years) hospitalized with this illness. Elderly patients with infectious mononucleosis were found to run a longer febrile course (13 vs. 7 days, p less than 0.01) and to have a lower peak total white blood cell count (6,600/mm3 vs. 11,000/mm3, p less than 0.001) and a lower incidence of splenomegaly (50% vs. 76%, p less than 0.05), lymphadenopathy (25% vs. 94%, p less than 0.001), and pharyngitis (25% vs. 47%, p less than 0.05), compared with young patients with infectious mononucleosis. Patients in both groups had a high prevalence of abnormal liver function tests. It is concluded that infectious mononucleosis in patients over 40 years of age is not as uncommon as previously reported, and that clinical and laboratory features differ between young and older patients suffering from this disease. PMID- 3344760 TI - Continuous 5-fluorouracil (5FU) infusion in carcinoma of the pancreas: a phase II study. AB - Sixteen patients with metastatic carcinoma of the pancreas were treated with continuous ambulatory 5-Fluorouracil (5FU) infusion (200-300 mg/m2/day) through a chronic indwelling central venous catheter. Twelve of sixteen patients (75%) had two or more sites of disease, and eleven of sixteen (69%) had liver metastases. Five patients had previous chemotherapy. RESULTS: partial remission, 3/16 (19%); stable disease, 8/16 (50%); and progressive disease, 5/16 (31%). Improvement in ECOG performance status was observed in 2/3 responding and 6/8 stable disease patients, respectively. Toxicities included hand-foot syndrome, mucositis, diarrhea, and cerebellar ataxia, which required treatment interruption in 9/16 patients (56%). No myelosuppression or catheter related problems were seen. The authors conclude that continuous infusion 5FU is a potentially efficacious palliative therapy in the management of carcinoma of the pancreas. PMID- 3344761 TI - Isolation of beta-hemolytic streptococci from the respiratory tract: distribution and clinical significance. AB - Isolates of beta-hemolytic streptococci obtained from respiratory tract specimens were studied for determination of their serogroup, and Patients' charts were reviewed for the clinical significance of these respiratory isolates. Fifteen of 69 patients were considered to have definite respiratory infection. Thirteen of these 15 patients had Group B beta-hemolytic streptococci. Staphylococcus aureus was isolated concomitantly with Group B streptococci (GBS) in 34% of cases, but rarely was it isolated with other beta-hemolytic streptococci. Sero-groups of beta-hemolytic streptococci were compared with respect to the patient's underlying disease, age, and clinical outcome. Patients who had GBS isolated from sputum were elderly (mean age, 68.1 years) and were older than patients with other beta-hemolytic isolates (mean age, 56 years). Patients with Group B streptococci were more likely to have cerebrovascular disease, whereas patients with Group C, G, and F were more likely to have malignancy, particularly of the head and neck. PMID- 3344762 TI - Agenesis of the corpus callosum, combined immunodeficiency, bilateral cataract, and hypopigmentation in two brothers. AB - We describe 2 brothers with a malformation syndrome consisting of agenesis of the corpus callosum, cutaneous hypopigmentation, bilateral cataract, cleft lip and palate, and combined immunodeficiency. The clinical history of both patients was characterized by severe psychomotor retardation, seizures, recurrent severe respiratory infections, and chronic mucocutaneous candidiasis. The children died of bronchopneumonia at age 2 and 3 years, respectively. Immunological investigations showed, in one sib studied, skin anergy to recall antigens, profound depletion of T4+ lymphocytes, and serum IgG2 deficiency. Necropsy showed agenesis of the corpus callosum, hypoplasia of the cerebellar vermis, and profound hypoplasia of the thymus and of the peripheral lymphoid tissue. The distinctive features of these sibs appear to define a previously undescribed hereditary MCA/MR syndrome. The clinical and pathological findings seem to indicate, as a pathogenetic mechanism, a defect involving the embryonic organization of the central nervous system and of the immune system. PMID- 3344763 TI - Distinctive syndrome of short stature, craniosynostosis, skeletal changes, and malformed ears. AB - We report on 2 unrelated boys with a distinctive facial appearance of microtia, atretic external auditory meati, small mandible, and microstomia, who also have a skeletal dysplasia, microcephaly, and joint contractures. The skeletal abnormalities, short stature, and microcephaly led to an initial diagnosis of osteodysplastic primordial dwarfism; however, the birth weight of one of the children is not low enough to firmly establish this diagnosis. The similarities were detected by the matching program of the London Dysmorphology Data-base. PMID- 3344764 TI - Hirschsprung disease in the offspring of mothers exposed to hyperthermia during pregnancy. AB - Interview data for events of pregnancy on 40 infants with Hirschsprung disease showed a significant relationship to a history of hyperthermia in the mother in the first trimester, during the time of embryonic development and migration of ganglion cells along the intestine. In order to eliminate maternal recall bias, a control group consisted of 41 malformed infants with congenital limb deficiency. Hyperthermia may be one factor contributing to the cause of some cases of Hirschsprung disease. PMID- 3344765 TI - Update on counseling the family with a first-degree relative with a congenital heart defect. AB - Updated recurrence risks figures are presented for genetic counseling of families with a congenital heart defect (CHD) in a first-degree relative. Substantial changes are recommended for counseling the family in which a parent has CHD. The risk is much greater if it is the mother rather than the father who has the heart defect. The updated figures for recurrence risks in sibs have been revised, but are not greatly changed. Our central tenet in counseling is to base risk projections on the genetic and teratogenic history in the individual family and pregnancy. PMID- 3344766 TI - Metacarpophalangeal pattern profile analysis in Sotos syndrome: a follow-up report on 34 subjects. AB - Metacarpophalangeal pattern profile (MCPP) was determined on 34 Sotos syndrome individuals and compared with previous MCPP studies. The mean hand profile contained a major peak in the proximal phalangeal area and a smaller peak in the metacarpal area, while the distal hand bones were relatively short. There appear to be three recognized hand profiles in Sotos syndrome, which suggests heterogeneity of the syndrome, although correlation studies indicate clinical homogeneity of individuals in the younger age groups. Discriminant analysis of Sotos syndrome versus control subjects produced a function of two MCPP variables, plus age, which may be applied as another diagnostic tool. PMID- 3344768 TI - Acrofacial dysostosis with postaxial limb deficiency. AB - Here we report on an adult man with the postaxial acrofacial dysostosis syndrome, as delineated by Miller et al [1979]. In addition to facial changes strikingly similar to that of the Teacher-Collins syndrome and a cleft soft and hard palate, symmetrical postaxial limb deficiencies with absence of the fifth digital rays in both the upper and lower limbs were present. PMID- 3344767 TI - Duplication 11q and deletion 5p syndromes due to a reciprocal translocation segregating in four generations. AB - We report on 2 relatives with duplication 11q and deletion 5p, resulting from an adjacent-1 segregation of a balanced reciprocal translocation 5p15;11q23, segregating in 4 generations of this family. Twelve out of 16 at-risk relatives of inheriting the translocation were shown to be carriers, giving a significant (p less than .05) 3:1 ratio of carriers/noncarriers. The breakpoint on chromosome 11 at q23 is a folate sensitive fragile site into where the proto-oncogene c-ets has been mapped. PMID- 3344769 TI - Sparse hair, short stature, hypoplastic thumbs, single upper central incisor and abnormal skin pigmentation: a possible "new" form of ectodermal dysplasia. AB - A family is described where a mother and three sons have an unusual form of ectodermal dysplasia that may have been described in the medical literature only once before. The unusual manifestations in this family are mild short stature, sparse scalp hair, skin pigmentation and a transient urticarial-like reaction on the hands and arms. The mother and one son demonstrated a single, upper central incisor and the mother and another son had hypoplastic thumbs. The mother alone had hyperkeratosis of the palms and soles. The inheritance pattern is most likely autosomal dominant, although X-linked dominant inheritance cannot be excluded. PMID- 3344770 TI - A professional partnership with genetic support groups. AB - Voluntary, lay genetic support groups have become important providers of supportive, educational, and social services for clients and families who face genetic disorders. A survey of 88 persons representing genetic support groups confirms that these organizations are providing their members with information and assistance about not only the genetic aspects of the disorders but also problems of daily living. Respondents noted that professionals frequently refer patients to their groups and that many of the groups have professionals working directly with them as guest lecturers, consultants, and advisory board members. At least 20% cited a lack of genetic counseling services for members of their groups as a serious problem and called for greater sensitivity to emotional concerns in the timing and delivery of genetic counseling by professionals. Respondents called for greater collaboration between the voluntary organizations and professionals but underscored the unique benefits of empathy and support from one's peers. PMID- 3344771 TI - Metacarpophalangeal pattern profile analysis in partial 9pmonosomy. PMID- 3344772 TI - Megalocornea and mental retardation syndrome. PMID- 3344773 TI - Pallister-Killian syndrome--an update of a clinical case. PMID- 3344774 TI - Familial risk of congenital heart defect. PMID- 3344775 TI - A case of ring (9)/del(9p) mosaicism associated with gastroesophageal reflux. AB - We present a male infant with r(9) and del(9p) mosaicism and chromosome constitution of 46,XY,r(9) (p22;q34)/46,XY,del(9) (p22). This patient also had gastroesophageal reflux with persistent regurgitation and resultant failure to thrive. The association of this syndrome with gastroesophageal reflux is emphasized. PMID- 3344776 TI - A syndrome of multiple congenital contractures: neuropathological analysis on five fetal cases. AB - We performed a neuropathological study on 5 fetuses with an autosomal recessive, lethal syndrome of congenital contractures diagnosed by fetal hydrops on ultrasonography. The fetuses showed a typical pattern of malpositioning of hips and knees with occasional pterygia of the neck and elbows. The muscles were hypoplastic and the spinal cords showed severe thinning, most markedly affecting the ventral half. A total loss of axons in the ventral and lateral funiculi, subtotal loss of anterior horn motor neurons with accompanying astrocytosis and astrogliosis, and similar but less severe changes at the brain stem level suggested a degenerative rather than a dysmorphogenetic mechanism. Sensory nuclei and pathways were distinctly less severely affected, if at all. The findings further delineate this condition as a genetically and pathoanatomically distinct autosomal recessive syndrome. PMID- 3344777 TI - Fetal akinesia deformation sequence in previable fetuses. AB - We reviewed the morphologic findings of 948 previable fetuses and identified the fetal akinesia deformation sequence (FADS) in 16 cases. In eight fetuses who had joint contractures, micrognathia, and pulmonary hypoplasia, the cause of fetal akinesia could be attributed to an abnormal intrauterine environment restricting fetal movement. The other eight fetuses had pterygia across the immobilized joints, in addition to main manifestations of FADS. Since most of the fetuses with pterygia were of only 8-9 weeks developmental age, we suggest that embryonic onset of immobility interferes with limb development and results in joint fixation and pterygium formation, in contrast to fetal-onset immobility, which causes joint contractures alone. PMID- 3344778 TI - Three cases of untreated classical PKU: a report on cataracts and brain calcification. AB - There are only four previous reports of cataracts in untreated classical phenylketonuria (PKU) patients. Brain calcification, which has been known to occur in patients with dihydropteridine reductase (DHPR) deficiency, has been reported, as far as we know, in only one (albeit unusual) case. We report on three patients with untreated classical PKU; all have cataracts and normal serum levels of glucose and galactose. One of the patients (whose endocrinological tests and biochemistry including folate were normal) has bilateral brain calcifications remarkably similar to that seen in DHPR deficiency. To what extent cataracts and brain calcification occur with classical PKU is unknown because of the lack of case reports addressing these symptoms. Our cases combined with previous reports call attention to the fact that they may be frequently overlooked manifestations of classical PKU. PMID- 3344780 TI - A new acro-cranio-facial dysostosis syndrome in sisters. AB - Two sisters born to consanguineous parents had a syndrome of short stature, acrocephaly, hypertelorism, proptosis, ptosis, down-slanting palpebral fissures, high nose bridge and anteverted nares, short philtrum, cleft palate, micrognathia, abnormal external ears, preauricular pits, sensorineural and conductive deafness, proximally placed first toes and digitalized thumbs, bulbous digits, metatarsus adductus, and pectus excavatum. Radiological abnormalities included craniosynostosis, increased mandibular angle and antegonial notching of mandible; hypoplastic first metacarpals and metatarsals; hypoplastic distal phalanges; partial duplication of the distal phalanx of the thumb; malformed malleus and incus; tall lumbar vertebrae, increased interpedicular distance, and posterior scalloping; flared iliac wings, narrow supraacetabular regions, acetabular "dysplasia," and coxa valga. Autosomal recessive inheritance is suggested. PMID- 3344779 TI - Parental origin of the extra chromosome in the cat eye syndrome: evidence from heteromorphism and in situ hybridization analysis. AB - Two individuals, a boy and girl, with a clinical diagnosis of cat eye syndrome had an extra bisatellited chromosome. In the girl, the diagnosis was made on the basis of coloboma of the right iris, right preauricular pit, and imperforate anus; in the boy, bilateral colobomata of the iris, down-slanting palpebral fissures, right preauricular skin tag, and right preauricular pit. Multiple staining techniques were used to characterize the extra chromosomes. With G banding the extra chromosome usually appeared monocentric with two major G positive bands, but with satellites on both ends; with C-banding, two C-band positive regions were evident, indicating that the chromosomes were likely dicentric. Silver staining demonstrated the presence of NORs near each end; Q banding showed satellites on each end, differing in brightness and size. The chromosomes of the parents were normal; comparisons of Q-band heteromorphisms of the acrocentric chromosomes of the parents with those of the extra chromosome showed in each case one short arm/satellite region of the extra chromosome identical in appearance to one chromosome 22 of the mother and the other end of the extra bisatellited chromosome identical to the short arm/satellite of the mother's second chromosome 22. This extra chromosome, then, is the result of a maternal meiotic error in each case. In situ hybridization studies using the chromosome 22-derived probe p22/34, which identifies locus D22S9, showed 16% of the cells from the female patient to have silver grains on the proximal long arm of the normal chromosome 22 and 14% on the extra chromosome, while 10% of cells from the male had grains on the normal chromosomes 22 and an equal number on the extra chromosome, confirming the chromosome 22 origin of the extra chromosome in these patients. PMID- 3344781 TI - Long-term corneal endothelial changes after intraocular lens implantation. AB - We studied the morphologic characteristics of the corneal endothelium in a series of patients who had undergone phacoemulsification with intraocular lens implantation performed by one surgeon. Specular microscopy and computer-assisted morphometry were performed preoperatively and three years after surgery. Nineteen eyes that received posterior chamber lenses with intracapsular fixation had a mean endothelial cell loss of 18.1%, without any significant change in cell size (polymegethism) or shape variability (pleomorphism). Implantation of anterior chamber lenses with the posterior capsule left intact (18 eyes) caused a similar degree of cell loss (23.5%) but caused marked polymegethism and pleomorphism of the cells. Endothelial cell loss (28.5%) and morphologic changes were greatest in five eyes that received anterior chamber lenses because of a rupture of the posterior capsule. PMID- 3344782 TI - Maternal corneal thickness during pregnancy. AB - We measured central corneal thickness in 89 pregnant women. It was increased 16 micron (P = .01) compared to the control eyes of 18 nongravid and 17 postpartum women. There was no significant difference (P = .79) in corneal thickness between the nongravid and postpartum groups. When comparing subjects by week of gestation, there was no trend over time in corneal thickness (analysis by linear regression). Intraocular pressure was lowered during pregnancy, but it did not correlate with corneal thickness for either the pregnant or nonpregnant group. PMID- 3344783 TI - Enlargement of the blind spot caused by papilledema. AB - Blind spot enlargement in papilledema has been attributed to either mechanical disruption of the integrity of the peripapillary percipient elements by the swollen optic disk or to the Stiles-Crawford effect. We investigated the possibility that blind spot enlargement in papilledema is caused, at least in part, by a refractive scotoma due to peripapillary hyperopia. We reduced the enlarged blind spot in a patient with focal peripapillary hyperopia, without papilledema, to near normal size by using progressively stronger plus lenses. Similarly, with the addition of plus sphere, we reduced the size of the blind spot in five of six patients with papilledema, but in none of our normal subjects. PMID- 3344784 TI - Unusual central chorioretinitis as the first manifestation of early secondary syphilis. AB - Three young, otherwise healthy patients had a similar picture of unilateral central chorioretinitis associated with severe visual loss. Fluorescein angiography disclosed diffuse leakage under the neurosensory retina in the posterior pole, associated with multifocal areas of staining along the retinal vessels. Systemic examination showed a positive fluorescent treponemal antibody absorption test and a sharp increase in VDRL titers, indicative of active secondary syphilis. The patients responded dramatically to penicillin treatment, with visual recovery and resolution of the fundus lesions. PMID- 3344785 TI - Anterior proliferative vitreoretinopathy. AB - During a four-year period, 53 of 92 eyes (58%) undergoing vitreoretinal surgery for a retinal detachment with proliferative vitreoretinopathy demonstrated anterior proliferative vitreoretinopathy. We classified anterior proliferative vitreoretinopathy according to tractional direction, location, extent, and severity. Initially, the eyes were treated with a high scleral buckle and laser endophotocoagulation as an adjunct to vitrectomy. Treatment then evolved into a direct approach in which the anterior proliferative tissue was surgically cut or excised. Of the 42 eyes followed up for at least six months, 25 (59%) were totally reattached and 18 (43%) had a visual acuity of 5/200 or better. PMID- 3344786 TI - Pigmentary changes in acquired retinoschisis. AB - We reviewed retrospectively the records of patients referred for retinal examination and found 375 eyes (233 patients) with acquired retinoschisis. Of the 375 eyes, 85 had outer layer retinal breaks, 27 had retinal detachments, and 29 had pigmentary lines. Twenty-five of the 29 pigmentary lines (86.2%) demarcated either retinal detachment or outer retinal layer breaks. PMID- 3344787 TI - Fadenoperation for the management of complicated incomitant vertical strabismus. AB - We reviewed retrospectively the records of 17 patients with incomitant vertical diplopia secondary to an underacting inferior rectus muscle who had been treated by surgically weakening the contralateral inferior rectus muscle with a posterior fixation suture (fadenoperation). This was the sole procedure in four patients with blowout fractures and in two patients with restriction secondary to scleral buckling procedures. It was combined with horizontal or vertical muscle surgery in 11 patients. The procedure was particularly useful in preventing diplopia on downgaze after excessive weakening of a tight inferior rectus muscle in seven patients with thyroid ophthalmopathy. In three patients it was used in anticipation of an iatrogenic incomitancy in downgaze secondary to a large recession of a tight inferior rectus muscle. All patients were markedly improved after surgery and no complications were encountered. PMID- 3344789 TI - The oral examinations of the American Board of Ophthalmology and the Appointment Panel System. PMID- 3344790 TI - Pseudophakic pigmentary glaucoma. PMID- 3344791 TI - Intraocular dapiprazole to reverse mydriasis during extracapsular cataract extraction. PMID- 3344788 TI - Negative antibody response to long-term treatment of facial spasm with botulinum toxin. AB - Over a period of 163 weeks, 223 injections of botulinum A toxin were administered to 38 patients with facial spasm syndromes. The maximum cumulative toxin dose was 553 units, the maximum number of injections in any given patient was 16, and the maximum dosage of any given injection was 52.5 units. Sera from these patients showed no antibody production when measured with a standard mouse lethality bioassay. PMID- 3344792 TI - Canalicular laceration at birth. PMID- 3344793 TI - A modification in the frontalis suspension procedure. PMID- 3344794 TI - Incidence of subcortical lesions not increased in nonarteritic ischemic optic neuropathy on magnetic resonance imaging. PMID- 3344795 TI - Can the risk of acetazolamide-induced aplastic anemia be decreased by periodic monitoring of blood cell counts? PMID- 3344796 TI - Stress in black, low-income, single-parent families: normative and dysfunctional patterns. AB - Stressful life events and the effects of demographic and social network variables were explored in a study of 50 clinic-referred and 76 nonclinic, black, low income, single-parent families. Dysfunctional families evidenced greater stress and social network characteristics were not significant mediators. The family's internal resources may be the most important buffer against stress. PMID- 3344797 TI - Decision-making in cases of intrafamilial child sexual abuse. AB - In intrafamilial sexual abuse, the mother's functioning (her dependency, relationship with the victim, and protectiveness) and the father-offender's functioning (his overall functioning, guilt about victimization, and extent of sexual abuse) can be used to make decisions about removal of children, treatment prognosis, treatment strategies, and juvenile or criminal court action. Guidelines for clinicians are presented. PMID- 3344798 TI - A hierarchical model for evaluation of child sexual abuse. AB - Many symptoms and kinds of behavior have been reported as sequelae to sexual abuse in childhood. A hierarchical model is proposed that will help diagnosticians to integrate the child's symptomatology into their evaluations of possible sexual abuse. The relevance of the specific presentation of symptoms to treatment planning is discussed. PMID- 3344799 TI - Ethnic factors in group process: cultural dynamics in multi-ethnic therapy groups. AB - A framework is presented that was generated by clinical experiences with Asian clients in predominantly Caucasian therapy groups. Focus is on the impact of differing perceptions of power, authority, interpersonal boundaries, and family process on group dynamics. The applicability of this framework to other ethnic minorities is evaluated. PMID- 3344800 TI - Characteristics of female adolescent sexual offenders. AB - Descriptive data on a group of female adolescent sexual offenders seen in an outpatient clinic are presented, with characteristics of offenders, offenses, and victims. Unlike female adult sexual offenders of previous studies, these adolescents committed offenses without coercion from male co-offenders starting at an early age. Results are discussed with reference to gender differences among adolescent sexual offenders. PMID- 3344801 TI - Mutual aid for affective disorders: the manic depressive and depressive association. AB - A study of 188 participants in the founding chapter of the National Depressive and Manic Depressive Association revealed characteristics of patient and family members, their satisfaction levels with various aspects of the association, and their perceptions of outcome. PMID- 3344802 TI - Elementary students in classes for the emotionally disturbed: characteristics and classroom behavior. AB - Data are presented on 147 elementary students enrolled in special-education classes for the emotionally disturbed/behaviorally disordered, housed in self contained classrooms within the regular public schools of a large urban district. Demographic, psychiatric, academic, and observational characteristics were assessed. From these data, inferences are made about the needs of children enrolled in these classes. PMID- 3344803 TI - Psychological and behavioral correlates of family violence in child witnesses and victims. AB - Abused and nonabused child witnesses to parental violence temporarily residing in a battered women's shelter were compared to children from a similar economic background on measures of self-esteem, anxiety, depression, and behavior problems, using mothers' and self-reports. Results indicated significantly more distress in the abused-witness children than in the comparison group, with nonabused witness children's scores falling between the two. Age of child and types of violence were mediating factors. Implications of the findings are discussed. PMID- 3344804 TI - Child maltreatment and teenage first births: a relationship mediated by chronic sociodemographic stress? AB - Data were obtained from low-income, single-parent mothers for a test of the "life course" hypothesis that chronic stress mediates the relationship between teenage motherhood and both physical abuse and neglect of children. Large numbers of live births, a life history of unemployment, and low educational achievement were the measured stressors. Findings support the hypothesis, showing the number of live births as the most important mediator for both types of maltreatment. PMID- 3344805 TI - Influence of calcium on phosphate transport in cultured kidney epithelium. AB - Renal epithelia cultured from opossum kidney (OK) cell line were exposed to high- and low-Ca media (HCaM and LCaM, respectively). Changing the extracellular Ca concentration from 2.0 mM to 0.02 mM stimulated sodium-dependent Pi transport (NaPiT) of OK epithelia. The effect was detectable after 1 h of LCaM exposure and reached a maximal value at 4 h (HCaM, 1.49 +/- 0.02; LCaM, 2.71 +/- 0.02 nmol.mg prot-1.4 min-1, P less than 0.001), this difference remaining constant up to 16 h. The Na-dependent transports of both alanine and methyl-alpha-D glucopyranoside, a glucose analogue, were not affected by LCaM. Kinetic analysis of NaPiT revealed an increase in Vmax with no change in the apparent Km. The cellular adenosine 3',5'-cyclic monophosphate production was not affected by LCaM. In OK epithelia pretreated with either cycloheximide or actinomycin D the LCaM stimulatory effect was completely abolished. In the presence of 10(-9) to 10(-7) M bovine parathyroid hormone (1-34), the effect of LCaM on NaPiT was markedly blunted. In conclusion, this study in cultured kidney epithelia demonstrates that the renal NaPiT can be directly and selectively stimulated by lowering the extracellular Ca concentration. This effect required the de novo synthesis of proteins. The results also indicate that parathyroid hormone antagonizes the stimulatory effect of extracellular Ca on the renal transport of Pi. PMID- 3344806 TI - Sex differences in renal hemodynamics in rats. AB - These studies were designed to investigate sex differences in renal hemodynamics under control conditions and in response to two different cyclooxygenase inhibitors. Studies were performed under anesthesia in males, females, and ovariectomized (OVX) rats and in separate groups of conscious, chronically catheterized male and female rats of a different strain. In the control periods, before cyclooxygenase inhibition, the male kidney was vasodilated relative to the female. Because male and female rats have the same number of glomeruli per kidney, the total vascular resistance per glomerulus is substantially greater in females than males. Cyclooxygenase inhibition in the anesthetized intact female rat produced significant increases in single-nephron glomerular filtration rate, glomerular plasma flow rate, glomerular filtration rate, and renal plasma flow, whereas afferent and efferent arteriolar resistances and renal vascular resistance fell. In contrast, anesthetized male and OVX female rats showed no renal hemodynamic response to cyclooxygenase inhibition. In the absence of anesthesia and recent surgery, intact awake female rats responded similarly to conscious male rats in that neither showed any response to cyclooxygenase inhibition. These data suggest a functional sex difference in both baseline renal hemodynamics and the renal response to cyclooxygenase inhibition, the latter unveiled by surgical stress. PMID- 3344807 TI - Effect of Ca2+ on Cl- transport in thin ascending limb of Henle's loop. AB - Effects of ambient Ca2+ concentration on Cl- transport across the thin ascending limb of Henle's loop (TAL) were examined by the in vitro microperfusion technique. When Ca2+ concentration in the bathing fluid was decreased from 1.5 mM to nominally 0 mM at 37 degrees C, the relative permeability of Cl- to Na+ (PCl/PNa) estimated from the NaCl diffusion voltage changed from 2.44 +/- 0.20 to 1.27 +/- 0.16 (n = 7, P less than 0.01). When Ca2+ concentration of the luminal fluid was reduced, PCl/PNa was unchanged. When Ca2+ concentration in the bathing fluid was changed from 4.5 to nominally 0 mM, the lumen-to-bath flux coefficient for 36Cl (K36Cl(l----b)) was decreased, whereas the value for 22Na was unchanged, indicating that the reduction of Ca2+ concentration in the bathing fluid selectively inhibits Cl- transport without affecting Na+ transport. By contrast, at 23 degrees C, the elimination of Ca2+ from the bathing fluid caused only a small reduction of PCl/PNa. Although at 23 degrees C acidification of the bathing fluid caused only little or no decrease in Cl- permeability, the elimination of Ca2+ from the bathing fluid under acid pH markedly suppressed the (K36Cl(l----b)) (10(-7) cm2/s). The pH titration curves of relative Cl- permeability examined at three different Ca2+ concentrations at 37 degrees C revealed that the interaction between proton and Ca2+ was noncompetitive. Addition of quin 2-AM, which reduced intracellular Ca2+ concentration, to the bath caused an irreversible suppression of Cl- permeability, suggesting that the decrease in intracellular Ca2+ concentration also inhibits the Cl- transport across the TAL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344808 TI - Effect of angiotensin II on Ca2+ kinetics and contraction in cultured rat glomerular mesangial cells. AB - This in vitro study was undertaken to determine the changes in Ca2+ kinetics and cell shape of cultured putative glomerular mesangial cells in the rat in response to angiotensin II (ANG II). Intracellular Ca2+ ([Ca2+]i) was measured using quin 2. ANG II-stimulated Ca2+ efflux was also determined. ANG II induced rapid concentration-dependent increases in [Ca2+]i and Ca2+ efflux. ANG II also induced contraction of mesangial cells as assessed by alterations in cell shape. Even in Ca2+-free medium, ANG II increased [Ca2+]i and Ca2+ efflux, but to a lesser extent. Under this condition, contraction of mesangial cells induced by ANG II was also observed. Readdition of extracellular Ca2+ after the ANG II-induced increase in [Ca2+]i caused a second and slower [Ca2+]i increase. High potassium (50 mM) induced a change of [Ca2+]i, but to a lesser extent compared with the ANG II-induced change. The Ca2+ channel blocker verapamil (5 x 10(-5) M) partially inhibited ANG II-induced Ca2+ influx but totally blocked the increase in [Ca2+]i induced by high potassium. Verapamil did not inhibit ANG II-stimulated Ca2+ efflux or the change in cell shape. Dantrolene (10(-4) M), a blocker of Ca2+ release from endoplasmic reticulum, inhibited ANG II-stimulated Ca2+ efflux and change in cell shape. These results indicate that ANG II rapidly increases [Ca2+]i in cultured rat mesangial cells, in part by mobilizing Ca2+ from dantrolene-sensitive intracellular pools and in part through activation of receptor-operated and voltage-dependent Ca2+ channels. The [Ca2+]i mobilization, however, seems to be the primary modulator of initial glomerular mesangial cell contraction. PMID- 3344809 TI - Remnant kidney hypermetabolism and progression of chronic renal failure. AB - To investigate the mechanisms whereby verapamil and dietary phosphate restriction slow progression of nephron loss after renal ablation, the effects of these maneuvers on inulin clearance (CIn), net sodium reabsorption (TNa+), oxygen consumption (QO2), and net glucose production (GP) were examined in isolated perfused normal and remnant kidneys. Preliminary studies characterized the isolated perfused remnant kidney perfusion. Adaptation to renal ablation was greater for QO2 (102% of normal), GP (138%), and kidney weight (79%) than CIn (51%) or TNa+ (40%). Verapamil (50 microM) lowered QO2 in remnant kidneys (1.64 +/- 0.24 vs. control 2.86 +/- 0.16 mumol.min-1.g-1, P less than 0.005), as did phosphate restriction (1.81 +/- 0.22 vs. control 3.05 +/- 0.40 mumol.min-1.g-1, P less than 0.05). These effects could not be accounted for by changes in CIn, TNa+, or GP and were not observed in normal kidneys. In summary 1) remnant kidneys are hypermetabolic compared with normal kidneys when assessed by QO2 and GP; 2) verapamil and phosphate restriction diminish the enhanced metabolic activity of remnant kidneys, an effect that is independent of TNa+; and thus 3) verapamil and phosphate restriction may slow progression of renal disease, at least in part by reducing renal metabolic demands. PMID- 3344810 TI - Loss of renal blood flow autoregulation in chronic glomerulonephritic rats. AB - Autoregulation of renal blood flow (RBF) was investigated in subacute (2 mo) and chronic (18 mo) passive Heymann nephritis (PH-2, PH-18) and age-matched controls (C-2, C-18). RBF was significantly lower in PH-18 than in C-18 (3.7 +/- 0.4 vs. 4.7 +/- 0.5 ml.min-1.kidney-1; P less than 0.05), whereas the mean blood pressure (MAP) was similar. The creatinine clearance was significantly lower in PH-18 than in C-18 (1.89 +/- 0.5 vs. 3.15 +/- 0.77 ml.min-1.kg body wt-1; P less than 0.002). Kidney weight was significantly higher in PH-18 than in C-18 (P less than 0.002). In PH-2 and C-2, RBF, MAP, creatinine clearance, and kidney weight were not different (P greater than 0.10). In PH-18 the maximal reduction of the renal vascular resistance (RVR) during RBF autoregulation was 4 +/- 2%, compared with 24 +/- 4% in C-18 (P less than 0.002); the lower pressure limit of RBF autoregulation was 131 +/- 9 vs. 85 +/- 4 mmHg (P less than 0.002). In PH-2 the maximal reduction of RVR during RBF autoregulation was 18 +/- 3%; in C-2 it was 25 +/- 2% (P greater than 0.10); the lower pressure limit of RBF autoregulation was 101 +/- 4 vs. 84 +/- 6 mmHg (P less than 0.02). It is concluded that RBF autoregulation is nearly lost in the late stage of glomerulonephritis, possibly as a consequence of the nephron loss. PMID- 3344811 TI - Estimates of left ventricular interstitial fluid adenosine during catecholamine stimulation. AB - The hypothesis that changes in myocardial interstitial fluid (ISF) adenosine (Ado) concentrations couple coronary blood flow (CBF) with myocardial oxygen need is still controversial. Measurements of Ado in cardiac tissue, coronary sinus plasma, and pericardial infusates have commonly been used as indexes of ISF Ado, but recent studies have highlighted the potential invalidity of many of the assumptions underlying these sampling methods. With the use of an epicardial chamber (EC) to contain a small volume of buffer on the undisturbed left ventricular epicardium of anesthetized open-chest dogs, estimates of ISF Ado can be obtained without invoking these assumptions. In experiments designed to validate our method and investigate the role of Ado in the regulation of CBF during myocardial catecholamine stimulation, we found that endogenous Ado accumulated in the EC exponentially and attained constant steady-state concentrations, ranging from 75 to 125 nM, within 4 min. Intravenous infusions of two catecholamines increased steady-state EC Ado concentrations twofold, but did not affect Ado influx kinetics. We conclude that the EC technique yields more direct estimates of steady-state ISF Ado concentrations than previously available and that ISF Ado is involved in the mediation of the hyperemia accompanying myocardial catecholamine stimulation. PMID- 3344812 TI - Computer analysis of cardiovascular changes during sleep-wake cycle in Sprague Dawley rats. AB - Blood pressure (BP) and heart rate (HR) were recorded in seven Sprague-Dawley rats during a total of 491 normal sleep-wake cycles with the use of a computer assisted method developed for this study. Significant changes of BP, HR, and BP variability (BPV) were found between the three states within the cycle, i.e., wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS). The highest BP, BPV, and HR values were found during W. Then all cardiovascular (CV) variables fell during SWS, whereas BP and BPV rose again during PS. The fall of BPV observed during SWS was the most important CV change observed within the cycle. These state-dependent CV changes suggest that, in the rat, circulation during the sleep-wake cycle is controlled by the same central factors that operate in cats. In addition, significant BP and HR modifications between different cycles have been found. On the other hand, BP and HR differences between animals were also observed. The latter differences were found to be stable across the states, but no significant relation was found between BP and HR within any state. Thus the present data also suggest that BP and HR measurements are influenced not only by state-dependent factors but also by at least three different factors that are each independent of the state: one leads to BP and HR values that are influenced by the cycle the animal is in and the other two influence, respectively, the ranking of the individual's BP and HR levels within the population. PMID- 3344814 TI - Bioassay by cross-perfusion for circulating inotropic factor in hypertension. AB - To study inotropic effects of blood from one-kidney, one-clip (1K,1C) rats with early (less than 7 days) or chronic (greater than 4 wk) benign hypertension, we assessed arteriolar resistance and norepinephrine (NE) responses in vascularly isolated, innervated assay hindlimb vascular beds of alpha-chloralose anesthetized, normal male recipient rats. Hindlimbs were cross-perfused (2 ml/min) with blood from anesthetized donor rats with limb outflow returned to the donor rat. Perfusion pressure was monitored. Complete NE (injected intra arterially) dose-response curves in limbs perfused with donor blood from nine early 1K,1C rats, compared with nine appropriate normotensive control donor rats, indicated unchanged thresholds, 50% effective doses, and maximal responses. Curves in limbs perfused with blood from 10 chronic 1K,1C, compared with 10 appropriate controls, suggested small (P less than 0.02) leftward shifts. Decreases (P less than 0.01) in maximal responses were also observed. Limb resting resistance and minimal resistance (sodium nitroprusside) did not rise, even after 4-5 h of cross-perfusion. These results provide no evidence in early 1K,1C and little evidence in chronic 1K,1C that humoral factors, including ouabainlike inhibitors, evoke physiologically significant inotropic effects in arterioles in vivo. PMID- 3344813 TI - Release of adenosine from pig aortic endothelial cells during hypoxia and metabolic inhibition. AB - The purpose of this study was to determine the effects of acute hypoxia on the ATP content of, and release of adenosine from, cultured endothelial cells. Pig aortic endothelial cells grown on plastic dishes or on microcarrier beads were incubated in physiological saline and gassed to achieve normoxia (media PO2 = 80 85 mmHg) or hypoxia (media PO2 = 2-12 mmHg) in the presence and absence of glucose and dipyridamole. Acute hypoxia did not significantly augment adenosine release from cells but did appear to decrease the reuptake of adenosine by cells. Hypoxia of a longer duration (3 h) led to ATP degradation and increased adenosine release when glucose was absent from the incubating medium, but not otherwise. Similarly, incubation of cells with NaCN in a glucose-free medium led to an increase in extracellular adenosine accumulation, whereas NaCN in the presence of glucose did not increase the accumulation of adenosine above the control level. The results suggest that the adenine nucleotide metabolism of cultured endothelial cells is not acutely sensitive to hypoxia or to inhibition of oxidative metabolism and can be maintained by glycolysis. PMID- 3344815 TI - Osmolality-mediated Fahraeus and Fahraeus-Lindqvist effects for human RBC suspensions. AB - The effects of suspending medium osmolality (166 to 836 mosm/kg) on flow in narrow bore tubes (33- to 146-microns diameter) were studied for 40% hematocrit suspensions of human red blood cells (RBC) in buffer; concurrent measurements of viscosity (eta r) and tube hematocrit (HT) allowed evaluation of the Fahraeus Lindqvist effect (FLE) and Fahraeus effect (FE). The FLE and FE were present for all suspensions regardless of osmolality. Viscosity increased markedly for the hypertonic media, and the FLE was more pronounced for the hypertonic region; changes in eta r from 146 to 33 microns were -22% (220 mosm/kg), -34% (290 mosm/kg), and -45% (460 mosm/kg). In contrast, HT and hence the FE were relatively insensitive to osmolality (14% change over entire range of osmolality and diameter). Suspension viscosities in 33- and 146-microns tubes could not, in general, be accurately calculated using experimental HT values combined with eta r -HT data from 340-microns tubes; however, a semiempirical model indicated that 1) RBC number concentration in the tube and tube diameter per RBC volume are primary determinants of eta r, and 2) eta r can be predicted over a wide range of osmolalities and tube diameters. RBC transport efficiency was a function of both tube diameter and osmolality (maximum for 33 micron at approximately equal to 400 mosm/kg). Our results appear applicable to blood flow in nonisotonic regions of the circulation and to estimation of blood viscosity in microcirculatory vessels. PMID- 3344816 TI - Complement is not involved in monocrotaline pyrrole-induced pulmonary injury. AB - Monocrotaline pyrrole (MCTP) causes pulmonary vascular injury, pulmonary hypertension, and right ventricular hypertrophy in rats. The mechanisms by which MCTP causes lung injury are not known. After treatment with a moderate dose of MCTP, several days pass before major lung injury is detected, thus suggesting that the damage is caused indirectly. Since activation of the complement system can cause lung injury, it was of interest to test whether complement activation may be important in lung injury due to MCTP. Accordingly, rats were given a single dose of MCTP (3.5 mg/kg iv), and serum hemolytic complement activity was measured at several times after rats were treated. Neutrophil aggregometry also was used to determine whether complement activation products could be detected in serum after MCTP was given in vivo. The effect of complement depletion on MCTP induced pulmonary injury was tested by cotreating rats with purified cobra venom factor and MCTP. MCTP treatment did not cause detectable complement activation in vivo, and complement depletion did not protect rats from lung injury. The direct effect of MCTP on serum complement also was tested by exposing fresh rat serum to MCTP in vitro and measuring serum complement activity. MCTP decreased serum hemolytic complement activity in vitro, but it did not interfere with subsequent zymosan-induced activation of complement. These results suggest that complement does not play a role in the development of major lung injury that occurs several days after treatment of rats with MCTP. PMID- 3344817 TI - High-intensity exercise training increases vascular transport capacity of rat hindquarters. AB - The purpose of this study was to determine whether high-intensity exercise training increases the vascular flow capacity and capillary exchange capacity in isolated rat hindquarters. One group of 20 male Sprague-Dawley rats underwent six bouts of alternating running (2.5 min) and recovery (4.5 min), 5 days/wk at 60 m/min on a 15% grade for 6-10 wk (high-intensity exercise training), while a second group of 20 rats was cage confined (sedentary controls). Experiments were conducted in isolated, maximally dilated (papaverine) hindquarters perfused with an artificial plasma consisting of a Tyrode's solution containing 5 g/100 ml albumin. Vascular flow capacity was evaluated by measuring perfusate flow rate at four different perfusion pressures. Capillary exchange capacity was evaluated by measuring the capillary filtration coefficient. The efficacy of training was demonstrated by significant increases in succinate dehydrogenase activity in the white vastus lateralis and vastus intermedius muscles. Total hindquarter flow capacity was elevated 50-100% in the trained rats. This increased flow capacity was associated with an increase in the capillary filtration coefficient in the maximally vasodilated hindquarters, thus suggesting that the capillary exchange capacity was increased with high-speed exercise training. These results suggest that the vascular transport capacity in rat hindquarter muscles is significantly increased by high-intensity exercise training. PMID- 3344818 TI - Matching between feline left ventricle and arterial load: optimal external power or efficiency. AB - We tested the hypothesis that the feline left ventricle normally works at optimal external power as opposed to optimal efficiency by (re)analyzing data from five isolated, blood-perfused cat hearts and 39 open-thorax cats. In the isolated hearts, we measured pump function, external steady power, myocardial oxygen consumption, and efficiency. Optimal external power and optimal efficiency were found at different left ventricular outputs (6.94 +/- 0.33 and 8.35 +/- 0.37 ml/s, respectively; P less than 0.001). In the in situ cat hearts the working point was found at an output of 4.72 +/- 0.32 ml/s, whereas optimal external power was found at 4.84 +/- 0.26 ml/s. These values were not significantly different. Assuming that the point of optimal efficiency was located at the same fraction of the maximal unloaded left ventricular output (Fmax) as in the isolated hearts, i.e., 0.7, we found the point of optimal efficiency for the in situ heart at a flow of 5.83 +/- 0.32 ml/s, which was significantly different (P less than 0.001) from the flow in the working point. Our data therefore indicate that the left ventricle in the open-thorax cat is matched to the arterial load such that its external power output rather than efficiency is optimized. PMID- 3344819 TI - Effects of vasoactive stimuli on blood flow to choroid plexus. AB - The goal of this study was to examine effects of vasoactive stimuli on blood flow to choroid plexus. We used microspheres to measure blood flow to choroid plexus and cerebrum in anesthetized dogs and rabbits. A critical assumption of the microsphere method is that microspheres do not pass through arteriovenous shunts. Blood flow values obtained with simultaneous injection of 15- and 50-micron microspheres were similar, which suggests that shunting of 15-micron microspheres was minimal. Blood flow to choroid plexus under control conditions was 287 +/- 26 (means +/- SE) ml.min-1.100 g-1 in dogs and 385 +/- 73 ml.min-1.100 g-1 in rabbits. Consecutive measurements under control conditions indicated that values for blood flow are reproducible. Adenosine (5 microM.kg-1. min-1 iv) did not alter blood flow to cerebrum but increased blood flow to choroid plexus two- to threefold in dogs and rabbits. Norepinephrine (0.5 micrograms.kg-1.min-1) and phenylephrine (25 micrograms.kg-1.min-1) did not affect blood flow to cerebrum but decreased blood flow to choroid plexus by approximately 50%. We suggest that 1) the microsphere method provides reproducible valid measurements of blood flow to the choroid plexus in dogs and rabbits and 2) vasoactive stimuli may have profoundly different effects on blood flow to choroid plexus and cerebrum. PMID- 3344820 TI - O2 consumption of dog heart under decreased coronary perfusion and propranolol. AB - We compared the effects of decreased coronary perfusion pressure (CP) and propranolol on the relation between left ventricular O2 consumption (VO2) and systolic pressure-volume area (PVA). PVA represents total mechanical energy generated by contraction and is the area under the end-systolic pressure-volume (PV) line and systolic PV trajectory. In excised cross-circulated dog hearts, a decrease in CP from 82 (mean) to 51 mmHg decreased ventricular contractility index Emax (slope of end-systolic PV relation) by 17% (P less than 0.05) and slightly (P less than 0.05 in 3 of 11 hearts) lowered the VO2-PVA relation in a parallel fashion. A further decrease in CP to 32 mmHg decreased Emax by 56% (P less than 0.05) and considerably (P less than 0.05) lowered the VO2-PVA relation by decreasing both the VO2-axis intercept by 26% (P less than 0.05) and the slope by 24% (P less than 0.05) from control. Propranolol decreased Emax by 48% (P less than 0.05) and the VO2-axis intercept by 25% (P less than 0.05) without changing the slope (P greater than 0.05). We attributed the different response of the VO2 PVA relation to the difference of the coronary O2 supply-demand balance between decreased CP and propranolol. PMID- 3344821 TI - Autonomic modulation of atrioventricular conduction in ouabain-treated dogs. AB - There is a pronounced interaction between the two autonomic divisions in the control of some cardiac variables, e.g., heart rate and contractility; usually parasympathetic activation suppresses the sympathetic effects. There is controversy about whether a similar interaction occurs for atrioventricular (AV) conduction. We have previously been unable to describe such an interaction in adult dogs, although others found a sympathetic-parasympathetic interaction when the dog heart was paced at very short intervals (200-240 ms). We reasoned that a cardiac glycoside (ouabain 20 micrograms/kg iv), which accentuates the parasympathetic effect, might expose any autonomic interaction. The atrial and ventricular electrograms, heart period, and atrioventricular conduction time (A-A and A-V intervals) were measured in 18 anesthetized, open-chest adult dogs. The sinoatrial (SA) node was suppressed by injection of Nembutal (pentobarbital sodium) through the SA nodal artery, and the hearts were paced at 500- to 700-ms intervals. The sympathetic and vagus nerves were stimulated bilaterally at three levels before and after ouabain or a diluent was given. Data were analyzed by analysis of variance. We found that there was no significant sympathetic parasympathetic interaction (P greater than 0.05) even after ouabain had potentiated the vagal effect by up to 100%. Thus, in dogs, control of AV conduction time by either autonomic division is independent of activity of the other divisions when the cycle length is not abbreviated. PMID- 3344822 TI - Left ventricular function during chronic endotoxemia in swine. AB - Cardiac performance was studied in 15 chronically instrumented awake pigs during chronic endotoxemia (CET) induced by intravenous infusion of low doses of endotoxin. We sought to test the hypothesis that left ventricular inotropic state was depressed during the stage of chronic endotoxemia when cardiac output, heart rate, and left ventricular systolic pressures are elevated, termed "hyperdynamic sepsis". Left ventricular pressure, internal short axis diameter (SAX), pulmonary artery blood flow, and electrocardiogram were recorded. After initial surgical preparation, each pig was observed for 7-10 days to measure representative basal values. Each pig was then reoperated on day 10 to implant an endotoxin-loaded osmotic pump whose output, infused Salmonella enteritidis endotoxin at a rate calculated to be 10 micrograms.kg-1.h-1 for up to 7 days. Cardiac performance was monitored by measuring dP/dt, heart rate, stroke volume, end-diastolic diameter, percent change in diameter, and the slope of the end-systolic pressure diameter relationship (ESPDR). Data from the basal days were pooled and compared with the data obtained each day of CET by two-way analysis of variance. Ten of 15 pigs survived more than 2 days of CET; 5 died before the morning of the second CET day. The surviving pigs demonstrated elevated systolic pressures, left ventricular maximum rate of pressure development (+dP/dtmax and -dP/dtmax), heart rates, and cardiac output. However, both ESPDR and percent SAX shortening were significantly depressed during both CET days. We conclude that cardiac inotropic state is depressed during hyperdynamic sepsis as indicated by the load independent parameter ESPDR and confirmed by depressed percent SAX shortening. PMID- 3344823 TI - Effect of hemodilution on oxygen transport in arteriolar networks of hamster striated muscle. AB - Experiments were performed on the hamster cheek pouch retractor muscle to investigate the influence of isovolemic hemodilution on microcirculatory hemodynamics and the rate of oxygen transport to striated muscle. In 23 hamsters, measurements of red blood cell velocity, hematocrit, vessel diameter, segment length (L), hemoglobin oxygen saturation (SO2), and longitudinal SO2 gradient (delta SO2/L) were made in four branching orders of arterioles before and after isovolemic exchange with plasma. Hemodilution decreased systemic hematocrit from 52 to 33%. In first- through fourth-order arterioles, this degree of hemodilution resulted in an average decrease in microcirculatory hematocrit from 42 to 28% and average increases in red blood cell velocity, computed blood flow, and systemic arterial PO2 of 50, 30, and 10%, respectively. In addition, delta SO2/L was significantly smaller in second-, third-, and fourth order arterioles compared with control values. It was estimated that approximately 84% of the oxygen that diffused across the arteriolar network was transferred by diffusion to nearby venules and capillaries; the remaining oxygen was consumed by the surrounding tissue. Following hemodilution, the magnitude of diffusional transfer declined to 73%. Oxygen flow remained at its control level in the first-order arterioles and progressively increased above control with increasing branching order. The increased oxygen delivery to the capillary network after limited hemodilution can be attributed to a compensatory increase in blood flow, an increase in systemic arterial blood oxygenation, and a decrease in precapillary oxygen loss. PMID- 3344824 TI - Effects of age and training status on heart rate recovery after peak exercise. AB - Previous studies have shown that the kinetics of heart rate (HR) recovery are delayed in older individuals after exercise. This study was designed to determine whether this observation held when the variables of physical fitness and work intensity were controlled. Twenty male subjects were categorized into four groups (n = 5) according to age and fitness level (peak O2 consumption ml. kg-1.min-1): young trained (YT) 24 +/- 2 yr, 63 +/- 3 ml.kg-1. min-1; old trained (OT) 51 +/- 2 yr, 57 +/- 3 ml.kg-1.min-1; young untrained (YU) 25 +/- 3 yr, 44 +/- 2 ml.kg 1.min-1; old untrained (OU) 57 +/- 4 yr, 36 +/- 4 ml.kg-1.min-1. Bicycle ergometry exercise was performed in incremental stages to a maximally tolerated level of exertion, and HR was monitored continuously postexercise. Regression analysis of the fast (15-120 s) and initial slow (120-240 s) phases of recovery showed no effect of age on HR recovery when comparing YT vs. OT and YU vs. OU. Trained subjects, irrespective of age, demonstrated a significantly faster HR recovery than untrained subjects which was particularly marked during fast-phase recovery (P less than 0.005). These results indicate that the slower HR recovery previously reported in older subjects may be due to a failure to control for variables that influence recovery HR. PMID- 3344825 TI - Spatial heterogeneity of local blood flow and metabolite content in dog hearts. AB - Spatial variation (heterogeneity) of myocardial blood flow was studied under basal conditions in relation to four biochemical markers: creatine kinase (CK), lactate dehydrogenase (LDH), ATP, and glycogen. A total of 508 individual 0.5-g samples from the left ventricular free wall was studied in 12 dogs. Myocardial blood flow was measured by radioactive microspheres (15 micron diam) injected via a pigtail catheter into the left ventricle during light sedation (closed-chest flow measurements); following thoracotomy, a second set of microspheres was injected via a catheter into the left atrium (open-chest flow measurements, n = 5). In 27-54 samples/heart, myocardial blood flow, CK, LDH, protein, ATP, and glycogen were determined, permitting a direct correspondence between local blood flow and metabolic markers in each sample and an assessment of the spatial heterogeneity of flow and metabolite content. Correlations between myocardial blood flow per gram tissue and metabolite concentration per gram tissue in pooled data were weak but significant: partial correlation coefficients were 0.137 for CK (P = 0.024), 0.167 for LDH (P = 0.006), 0.341 for ATP (P less than 0.001), 0.123 for glycogen (P = 0.053), but not significant for protein vs. myocardial blood flow. The coefficient of variation, which defines the extent of spatial heterogeneity, averaged 20% for closed-chest flow measurements, 19% for open chest flow measurements, 22% for CK, 17% for LDH, 15% for protein, 8% for ATP, and 18% for glycogen; these values are over and above the variability due to the technique error, indicating a definite physiological spatial variability. The correlation between local blood flow and the studied metabolites can only explain a minor portion of the spatial heterogeneity of myocardial blood flow. Although a physiological link between blood flow and metabolite content for small regions of the heart is demonstrated, the true local variability of blood flow may be modulated predominantly by other factors. PMID- 3344826 TI - Aortic pressure reduction redistributes transmural blood flow in dog left ventricle. AB - We studied the effect of graded aortic blood pressure reduction on left ventricular (LV) blood flow in anesthetized, autonomically blocked, open-chest dogs at constant heart rate and mean left atrial pressure. Aortic diastolic pressure (ADP) was lowered from rest (average 116 mmHg) to 90, 75, and 60 mmHg with an arteriovenous fistula. Global and regional LV blood flow was measured with radioactive microspheres. Mean LV blood flow fell stepwise from 145 ml.min 1.100 g-1 at rest to 116 ml.min-1.100 g-1 at ADP of 60 mmHg, whereas the endocardial-to-epicardial flow ratio decreased from 1.20 to 0.84. The transmural redistribution of LV blood flow was not accompanied by increases in LV oxygen extraction, depression of LV contractility, LV dilatation or LV electrical dysfunction and also occurred in the presence of considerable coronary vasodilator flow reserve. Electrical evidence of subendocardial ischemia appeared at ADP of 32 mmHg and an endocardial-to-epicardial flow ratio of 0.41 in a subgroup of animals. We conclude that the redistribution of LV flow during moderate aortic pressure reduction was an appropriate physiological adjustment to uneven transmural alterations in regional LV wall stress and that it preceded a more pronounced redistribution evident with myocardial ischemia. PMID- 3344827 TI - Adenosine handling in interstitia of cremaster muscle studied by bioassay. AB - We used video-microscopic techniques to study responses of rat cremaster muscle arterioles to adenosine (ADO) placed in a bathing solution in an effort to determine 1) the sensitivity of these vessels to local interstitial ADO concentration and 2) the parameters of interstitial adenosine handling. Two vessels, located at different depths (approximately 40 and 115 microns) below the surface of the tissue, were studied simultaneously. Invariably, a higher bath ADO concentration was required to induce vasodilation in the deeper vessel; the concentration required for 50% dilation response (EC50) for ADO dilation increased at an average of 1.8 +/- 0.2 log10 U/100 microns of depth into the tissue. This result was shown to be due to a standing gradient in interstitial ADO concentration. By extrapolating results to the tissue surface, we estimate that the EC50 for arteriolar dilation to local interstitial ADO is approximately 0.1 microM. The steepness of the tissue ADO gradient indicates that the rate constant for interstitial ADO loss is near 0.24/s. The gradients for nonmetabolizable adenosine analogues were less than 1/10th as steep as that for ADO itself. Qualitatively similar results were obtained from experiments on hamster cremaster muscle preparations. PMID- 3344828 TI - Evaluation of baroreceptor reflex by blood pressure monitoring in unanesthetized cats. AB - The arterial baroreceptor control of the sinus node operating in unanesthetized conditions was evaluated in 10 cats in which blood pressure was recorded intra arterially and scanned by a computer to identify the "spontaneous" sequences of three or more consecutive beats in which systolic blood pressure (SBP) progressively rose and pulse interval (PI) progressively lengthened (type 1 sequences) or SBP progressively fell and PI progressively shortened (type 2 sequences). Many type 1 and 2 three-beat sequences were found; four-, five-, and six-beat sequences of either type were progressively less common, and sequences longer than six beats were almost never identified. The regression coefficient was 30% greater for type 1 than for type 2 sequences. However a prominent feature of either regression coefficient was a wide scattering in each cat (average variation coefficient 50.9 +/- 5.5%). The regression coefficient values were related to some extent to the PI but not to the SBP existing at the beginning of the sequence. Sinoaortic denervation dramatically reduced the number of sequences of either type. These data validate a method for collecting a large number of observations on the baroreceptor-heart rate reflex in physiological conditions. This method may improve understanding of baroreflex involvement in integrated cardiovascular regulation. PMID- 3344829 TI - Microvascular exchange and interstitial volume regulation in the rat: model validation. AB - A dynamic mathematical model is formulated and used to describe the distribution and transport of fluid and plasma proteins between the circulation, interstitial space of skin and muscle, and the lymphatics in the rat. Two descriptions of transcapillary exchange are investigated: a homoporous "Starling model" and a heteroporous "plasma leak model." Parameters used in the two hypothetical transport mechanisms are determined based on statistical fitting procedures between simulation predictions and selected experimental data. These data consist of interstitial fluid volume and colloid osmotic pressure measurements as a function of venous pressure for muscle and interstitial colloid osmotic pressure vs. venous pressure for skin. The values determined for the transport parameters compare well with data in the literature. The fully determined model is used to simulate steady-state conditions of hypoproteinemia, overhydration, and dehydration, as well as the dynamic response to changes in venous pressure and intravascularly administered protein tracers. Comparisons between the simulation predictions and experimental data for these various perturbations are made. The plasma leak model appears to provide a better description of microvascular exchange. PMID- 3344830 TI - Renal nerve and cardiovascular responses to cardiac receptor stimulation in rabbits. AB - It has been shown that a species difference exists among cats, dogs, and monkeys in the reflex response to cardiac sympathetic afferent stimulation with bradykinin (BK). This study was performed to determine the arterial blood pressure (ABP), heart rate (HR), and renal nerve activity (RNA) responses to epicardial BK applications in the intact and sinoaortic-denervated and vagotomized (SAD + Vx) rabbits. Eight rabbits were anesthetized with pentobarbital sodium. The heart was exposed and suspended in the epicardial cradle. The ABP, HR, and RNA responses were determined when 1 and 10 micrograms/ml BK were applied to the anterior surface of the left ventricle in the intact and SAD + Vx state. In both the intact and SAD + Vx rabbits, ABP, HR, and RNA were significantly reduced with epicardial BK. In the SAD + Vx rabbits, BK evoked small decreases in ABP and HR and no change in RNA after topical lidocaine. These results show the existence of a depressor response and decreases in HR and RNA in the rabbit mediated by the action of BK on cardiac sympathetic afferents. PMID- 3344831 TI - Dynamic changes in venous outflow by baroreflex and left ventricular distension. AB - We examined the dynamic changes in venous outflow from the splanchnic and extrasplanchnic vascular beds in response to carotid sinus (CS) baroreflex and left ventricular (LV) distension in 12 dogs anesthetized with pentobarbital sodium. Splenic sympathetic nerve activity was measured in an additional group of six dogs. A heart-lung bypass was used with constant cardiac output and constant venous pressure. LV distension was produced by inflating a balloon in the LV. LV distension and an increase in CS pressure from 50 to 200 mmHg decreased blood pressure by 26 +/- 5 and 30 +/- 6 mmHg and increased vascular capacitance by 5.5 +/- 0.9 and 4.5 +/- 1.2 ml/kg, respectively. Splanchnic venous outflow exhibited a transient decrease, whereas extrasplanchnic venous outflow showed a transient increase, in response to LV distension and increasing CS pressure, accompanied by a sustained decrease in splenic nerve activity. The results indicate important differences between splanchnic and extrasplanchnic components of the total venous system in terms of the regulation of venous capacitance. It is suggested that changes in venous capacitance produced by LV distension and CS baroreflex are primarily due to active changes in splanchnic venous tone. PMID- 3344832 TI - Impact of acute corticosterone administration on feeding and macronutrient self selection patterns. AB - Food intake, body weight, and meal patterns in rats are known to be specifically influenced by circulating corticosterone (CORT). The present study examined, in Sprague-Dawley rats, the role of CORT in the regulation of caloric intake and choice of macronutrients during specific periods of the light-dark cycle. Adrenalectomy (ADX) significantly attenuated the ingestion of all three macronutrients, namely, protein, carbohydrate, and fat, in different test periods of the light-dark cycle. This deficit was significantly stronger just before or during the early dark hours, compared with the light period, and it was immediately CORT reversible. During this same early dark period, the stimulatory effect of CORT (0.5 or 2.0 mg/kg sc) on total food intake in ADX animals was also significantly stronger than during the light period. At this time, the CORT injected ADX animals consumed an even greater amount of total food intake than did the vehicle-injected sham-operated animals and showed a significant preference for carbohydrate, as opposed to no change or a decline in preference for protein or fat. These findings, in light of other evidence, suggest that CORT ensures and stabilizes the ingestion of all three macronutrients but, in particular, stimulates carbohydrate ingestion during the important feeding period at the dark onset when CORT levels normally peak. It is proposed that CORT may provide a critical signal, in conjunction with hypothalamic neurotransmitter systems, in the behavioral and metabolic regulation of body energy balance. PMID- 3344833 TI - Simultaneous measurement of preferred ambient temperature and metabolism in rats. AB - A recent study from this laboratory found that rats placed in a temperature gradient preferred ambient temperatures (Ta) that were significantly below the lower critical Ta of the thermoneutral zone for elevating metabolic rate (MR). To further evaluate the interaction between preferred Ta and MR in the rat, a system was developed where preferred Ta, MR (i.e., O2 consumption), and activity could be automatically monitored in the unrestrained rat. Two groups of male Sprague Dawley rats, a light-weight group and a heavy-weight group, were placed in a longitudinal temperature gradient for 90 min. These animals were further divided into two groups. One group was permitted free run in the gradient with a temperature range of 7-40 degrees C, whereas another group was restricted to the warm end of the gradient where the coolest available temperature was approximately equal to the lower critical Ta (29 degrees C). The preferred Ta and MR data were statistically analyzed over the last 20 min of the experimental run. Rats allowed to run freely in the gradient selected Ta of 17-20 degrees C and had MR significantly higher than animals restricted to a range of Ta no cooler than the lower critical Ta. Animals that selected the cooler Ta were much more active than those forced to remain at the warmer Ta. In conclusion, the interaction between behavioral and autonomic thermoregulation in the rat is unique compared with other rodent species such as the mouse, hamster, and guinea pig, which prefer Ta associated with thermoneutrality. PMID- 3344834 TI - Spectral analysis of heart rate variability of lizard, Gallotia galloti. AB - The beat-to-beat heart rate of the lizard, Gallotia galloti, at rest shows short term oscillations, the frequency of which varies with body temperature. Spectral analysis of the heart rate variability signal shows that, above 20 degrees C, two major frequency components are present: the first component has a mean frequency ranging from 0.032 at 20 degrees C to 0.070 Hz at 35 degrees C and the second from 0.039 at 20 degrees C to 0.10 Hz at 35 degrees C of body temperature. The beat-to-beat heart rate variability does not seem to be correlated with ventilatory activity. The two spectral components could be associated as in mammals with the activity of the control systems that regulate the circulation, especially with the cutaneous vasomotor thermoregulatory and endogenous pressure vasomotor activities. Transient interactions between both components are described. PMID- 3344835 TI - Diencephalic regions contributing to sympathetic nerve discharge in anesthetized cats. AB - We reported that the forebrain is responsible for a significant component (38%) of inferior cardiac postganglionic sympathetic nerve discharge (SND) in baroreceptor-denervated cats anesthetized with alpha-chloralose [Huang et al., Am. J. Physiol. 252 (Regulatory Integrative Comp. Physiol. 21): R645-R652, 1987]. The current study was initiated to assess the contribution of various diencephalic regions to the forebrain-dependent component of SND in this preparation. For this purpose, the reductions in inferior cardiac SND and blood pressure produced acutely by midbrain transection at stereotaxic plane A3 in nonlesioned control cats were compared with those in cats in which diencephalic lesions were made with radio-frequency current. Lesions of the anterior medial hypothalamus including the paraventricular nucleus failed to attenuate the decreases in SND and blood pressure produced by midbrain transection. In contrast, the effects of midbrain transection were significantly attenuated by lesions of the lateral hypothalamus (including medial forebrain bundle), posterior medial hypothalamus, or the medial thalamus. We conclude that both the hypothalamus and medial thalamus contribute to SND in anesthetized cats. PMID- 3344836 TI - Cat diencephalic neurons with sympathetic nerve-related activity. AB - In a companion paper, we demonstrated that hypothalamic or medial thalamic lesions attenuate the reduction in inferior cardiac postganglionic sympathetic nerve discharge (SND) produced by decerebration in the anesthetized cat [Huang et al., Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R249-R256, 1988]. This raised the possibility that these diencephalic regions contain the cell bodies of neurons that contribute to SND. The current study tested this possibility in cats anesthetized with alpha-chloralose. Spike-triggered averaging of inferior cardiac SND revealed the existence of two types of hypothalamic and medial thalamic neurons with sympathetic nerve-related activity. Recordings were made from the soma-dendritic region of these neurons, since an inflection often appeared on the rising phase of the unit action potential. The activity of type 1 neurons was synchronized to an aperiodic spikelike event in SND, whereas that of type 2 neurons was synchronized to a 2- to 6-Hz rhythmic component. Some of the type 2 neurons but none of the type 1 neurons had cardiac-related activity. Microstimulation at type 1 and type 2 unit recording sites increased SND. Our results are consistent with the possibility that hypothalamic and medial thalamic neurons contribute to the rhythmic and aperiodic components of SND in the anesthetized cat. PMID- 3344837 TI - Spinoreticular cell responses to renal venous and ureteral occlusion. AB - Responses of 65 thoracolumbar spinoreticular neurons to renal vein or ureteral occlusion were studied in 40 alpha-chloralose-anesthetized cats. Cells were antidromically activated from the medial medullary reticular formation and all responded to somatic stimuli as well as renal nerve stimulation. Renal vein occlusion excited 17 of 40 cells. Activity increased from 6 +/- 1 to 13 +/- 2 spikes/s, with little adaptation. Depressor responses occurred in 9 cats and pressor responses in 12 cats. Pressor responses, but not depressor responses, were abolished by renal denervation. Ureteral occlusion increased activity of 28 of 50 cells. Responses were always rapid in onset but were either nonadapting, slowly adapting, or completely adapting. Activity increased from 7 +/- 1 to a peak of 17 +/- 3 spikes/s. Pressor responses occurred in 22 of 25 cats and tachycardia in 15 cats. Transection of renal nerves abolished cardiovascular responses. Twenty-five cells were tested for responses for both stimuli. Ten were excited by both, six by only ureteral occlusion, and nine failed to respond to either. The responding group of cells had a significantly greater incidence of A delta- and C-fiber renal input compared with nonresponding cells. Nonresponding cells tended to have only A delta-input. The results show that renal and ureteral mechanical stimuli which evoke cardiovascular reflexes excite spinoreticular cells. These cells may be part of supraspinal reflex arcs initiated by renal receptors. PMID- 3344838 TI - Organization of energy provision in rainbow trout during exercise. AB - The purpose of this investigation was to examine the fuels supporting high intensity progressive exercise and their regulation within rainbow trout. During the sustained swim, red muscle (RM) used 97% (17.5 mumol/g) of its glycogen, whereas white muscle (WM) glycogen only declined 31% (7.3 mumol/g). During the burst swim, WM glycogen content decreased 10.4 mumol/g at a rate that exceeded the sustained swim rate by 6.2-fold. Lactate content increased 11-fold at a rate 25 times its sustained swim rate. The exhaustive swim resulted in a decrease of 36.6 mumol/g in liver glycogen, whereas WM glycogen content declined to very low values and lactate reached 43 mumol/g. RM glycogen levels remained low during these exercise bouts. Phosphocreatine (PCr)-buffered ATP declines (WM 7.3-2.7 mumol/g, RM 3.4-1.6 mumol/g) with the time course of the large ATP decreases being related to near depletion of PCr. Decreases in the total adenylate pool were compensated for by the accumulation of inosine 5'-monophosphate in both tissue types. Free ADP (ADPf) contents increased in both tissues by three- to fivefold. ATP/ADPf and cytosolic phosphorylation potentials decreased from 7- to 20-fold. Cytosolic redox potential remained relatively constant at approximately 145 within both fiber types. The changes in adenine nucleotide parameters are associated with the respective activation of the different fiber types and glycolytic flux. PMID- 3344839 TI - Septal neurons respond to activation of baro- and chemoreceptors in the rat. AB - Because it has recently been shown that selective activation of neuronal perikarya in the septal area elicits arterial depressor responses, it seems reasonable to expect that information from receptors in the cardiovascular system may be related to the septum. This possibility was investigated by searching for single units in the medial and lateral septal nuclei responding to activation of baroreceptors, elicited either by electrical stimulation of the aortic depressor nerve (ADN) or by systemic injection of phenylephrine (PE), or responding to activation of chemoreceptors, elicited by intracarotid injection of sodium cyanide. Fifty-four male Wistar rats weighing 300-400 g were anesthetized with urethan (1.4 g/kg ip) or alpha-chloralose-urethan (35 and 400 mg/kg ip, respectively) and allowed to breathe spontaneously. One-third of spontaneously firing units tested responded to ADN stimulation; these 93 units were divided into two groups according to their response patterns; 62 (67%) showed an increase and 31 (33%) a decrease in their discharge. Of 35 units tested, 6 responded to intravenous injection of PE. The majority of the units (48 of 60) affected by chemoreceptor activation were excited, and the remaining 12 were inhibited. These experiments suggest that sensory information from cardiovascular receptors may play an important role in the control of the circulation by the septum. PMID- 3344840 TI - Homeostatic potassium excretion in fed and fasted sheep. AB - In unanesthetized adult sheep, following intake of a daily meal, there was a peak in K excretion. The maximum and minimum rates of K excretion following meals were directly related to meal K content. On days without meals, no peak in K excretion occurred. Changes in K excretion on fed and fast days occurred without changes in the low levels of plasma aldosterone and were poorly correlated with urine or blood pH, urine flow rate, Na excretion, or the filtered load of K, but they correlated well with fractional K excretion. Plasma K did not change on fast days. Plasma K increased on some, but not all, fed days. Increases in plasma K that occurred on fed days were insufficient to account for the concurrent kaliuresis. Infusion of aldosterone or isotonic NaCl failed to alter K excretion in fed or fasted sheep. Infusion of isotonic NaCl + aldosterone hypertonic Na2SO4 + aldosterone increased K excretion in fasted but not fed sheep. Infusion of K in the rumen of fed and fasted sheep elevated rumen K concentration and led to increases in K excretion that could not be explained by increases in plasma K. The mechanisms responsible for the homeostatic changes in K excretion on fed and fast days were not ascertained but may importantly depend on sensors of enteric K content. PMID- 3344841 TI - Model of homeostatic regulation of potassium excretion in sheep. AB - Based on experimental observations on unanesthetized sheep, a hypothesis is proposed for the homeostatic control of potassium excretion in this ruminant. This hypothesis includes as a novel element a splanchnic sensor of potassium intake. Information provided by the splanchnic sensor contributes to the control of potassium excretion independently of the level of systemic plasma potassium or other conventional control factors. A mathematical model based on this hypothesis successfully simulates the relations between potassium excretion, plasma potassium, and oral and intravenous potassium input observed in sheep. PMID- 3344842 TI - Comparison of IR thermography and thermocouple measurement of heat loss from rabbit pinna. AB - The temperature of the pinnae of male New Zealand White rabbits was measured by use of infrared thermography. At ambient temperatures of 15, 20, and 25 degrees C, the average pinna temperatures were 23.0, 28.7, and 36.2 degrees C, respectively. From these temperatures, average heat loss from the total pinna surface area was calculated to be 2.8, 3.3, and 4.4 W, respectively. Preoptic temperature changes also affect the vasomotor state of the rabbit. At an ambient temperature of 20 degrees C, cooling the preoptic area of the rabbit by approximately 1 degree C resulted in an average pinna temperature of 26.5 degrees C and a heat loss of 2.4 W. Heating the preoptic area by approximately 1 degree C resulted in an average pinna temperature of 33.5 degrees C and a heat loss of 5.4 W. Finally, pinna temperatures were measured by use of a thermocouple and infrared thermography simultaneously. When the pinnae were vasodilated, the thermocouple measurements were consistently higher than the pinna surface temperatures measured thermographically. When the pinnae were vasoconstricted, the thermocouple measurements were consistently lower than the pinna surface temperatures measured thermographically. The discrepancy between the two methods of measurement is discussed. PMID- 3344843 TI - Striatal dopamine release and metabolism in sinoaortic-denervated rats by in vivo microdialysis. AB - The purpose of this study was to provide new evidence favoring the hypothesis that cardiovascular information from arterial baroreceptors is integrated with the nigrostriatal system that contributes to regulation of motor activity. Samples of extracellular striatal dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were collected by the technique of in vivo microdialysis and analyzed by high-performance liquid chromatography-electron capture detection. Rats were prepared with a guide tube placed in the caudate-putamen for subsequent insertion of microdialysis probes. During the 1st wk after sinoaortic denervation (SAD) or sham operation (SO), a microdialysis probe was inserted and perfused with Ringer solution at the rate of 2 microliter/min in the freely moving rats. Samples were collected every 20 min before and after injection of pargyline, 100 mg/kg ip. The results showed that SAD rats have approximately 50% less extracellular striatal DA, DOPAC, and HVA than SO rats (P less than 0.01). After blockade of monoamine oxidase activity with pargyline, striatal DA accumulated three times faster in SO than SAD rats suggesting DA synthesis is reduced in SAD rats. These data provide further evidence that the arterial baroreceptor system affects dopaminergic metabolism in the nigrostriatal system possibly as a means for integration of cardiovascular and motor activity. PMID- 3344845 TI - Dissociation and hypnotizability in posttraumatic stress disorder. AB - The authors compared the hypnotizability of 65 Vietnam veteran patients with posttraumatic stress disorder (PTSD) to that of a normal control group and four patient samples using the Hypnotic Induction Profile. The patients with PTSD had significantly higher hypnotizability scores than patients with diagnoses of schizophrenia (N = 23); major depression, bipolar disorder--depressed, and dysthymic disorder (N = 56); and generalized anxiety disorder (N = 18) and the control sample (N = 83). This finding supports the hypothesis that dissociative phenomena are mobilized as defenses both during and after traumatic experiences. The literature suggests that spontaneous dissociation, imagery, and hypnotizability are important components of PTSD symptoms. PMID- 3344844 TI - Depression and panic attacks: the significance of overlap as reflected in follow up and family study data. AB - Ninety-one patients with panic attacks limited historically to depressive episodes had more severe depressive symptoms and were less likely to recover during a 2-year follow-up than 417 depressed patients who did not have panic attacks. Family study data clearly distinguished another 15 patients with panic disorder and secondary depression; interviewed relatives of panic disorder patients were significantly less likely to have primary depression and significantly more likely to have various anxiety disorders. These data support the hierarchical system by which many of the contemporary diagnostic systems separate panic disorder and major depression. PMID- 3344846 TI - Low-dose neuroleptic therapy for children with childhood-onset pervasive developmental disorder. AB - An open study of the therapeutic effects of low-dose neuroleptic treatment was performed on 12 consecutively hospitalized children, aged 7-11, who satisfied DSM III criteria for childhood-onset pervasive developmental disorder. While receiving an average dose of 0.04 mg/kg per day of haloperidol or fluphenazine hydrochloride, the patients exhibited significant reductions in hyperactivity and aggressive symptoms and significant improvement in peer relations. This dose of neuroleptic was associated with minimal side effects. The authors conclude that low doses of potent neuroleptics may be effective treatment for some patients suffering from childhood-onset pervasive developmental disorder. PMID- 3344847 TI - Carbamazepine and hyponatremia in patients with affective disorder. AB - The authors assessed 20 carbamazepine-treated patients for the development of hyponatremia. None of the patients had readings below 135 meg/liter of sodium before carbamazepine therapy, but five (25%) did have such readings after carbamazepine therapy. Three of these patients developed frank symptoms of hyponatremia within 1-3 months of the start of therapy. In one patient, hyponatremia developed after rechallenge with carbamazepine. The authors suggest that caution be used in prescribing carbamazepine to patients with low or borderline low sodium values. PMID- 3344848 TI - Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients. AB - Low-dose scopolamine, given as presurgery medication, resulted in low levels of serum anticholinergic activity and caused measurable cognitive impairment in 18 psychiatrically healthy elderly patients. The degree of impairment was directly related to serum anticholinergic activity levels and, in the small subgroup of patients scheduled for spinal anesthesia, to CSF anticholinergic activity. Two of the mental status tests used, the Rey Auditory-Verbal Learning Test and the Saskatoon Delirium Checklist, were sensitive enough to detect these mild drug induced changes, while two other tests, the Mini-Mental State and the Symbol Digit Modalities Test, were not. PMID- 3344849 TI - The role of polysomnography in the differential diagnosis of chronic insomnia. AB - The authors examined the accuracy of the differential diagnosis of chronic insomnia with and without sleep laboratory studies in a consecutive series of 123 patients. All patients were evaluated by means of a sleep/wake log, a sleep habits questionnaire, structured psychiatric and clinical interviews, and a minimum of two consecutive nights of polysomnography. Notwithstanding a high rate of Research Diagnostic Criteria (RDC)-diagnosed psychopathology (63%) in this sample, the major finding was that in 49% of the patients laboratory results added to, refuted, and/or failed to support the clinical impression. This resulted in substantial modification of the initial diagnostic formulation and therefore in increased specificity of diagnosis. PMID- 3344850 TI - Idiopathic basal ganglia calcification and organic mood disorder. AB - Idiopathic basal ganglia calcification is a syndrome consisting of bilateral basal ganglia calcifications, neuropsychiatric abnormalities, disturbances of movement, and normal calcium and phosphorus metabolism. The best described neuropsychiatric alterations are dementia and an organic psychosis. Organic mood disorder has been reported less often, and mania secondary to idiopathic basal ganglia calcification has not been noted previously. The authors describe five patients with idiopathic basal ganglia calcification and organic mood changes, including one patient with secondary mania. Symptoms of idiopathic basal ganglia calcification resemble those of other disorders affecting subcortical structures and support an association between mood, affect, cognition, and the extrapyramidal nuclear system. Treatment may ameliorate the mood disorder. PMID- 3344851 TI - Psychiatric disorders in patients with cerebrotendinous xanthomatosis. AB - Cerebrotendinous xanthomatosis is a familial recessive disorder. Patients with the disorder present with tendon xanthomas, juvenile cataracts, dementia, and pyramidal and cerebellar abnormalities but have normal plasma cholesterol. High plasma cholestanol concentrations and abnormal bile acid metabolism are specific for this disease. The authors describe four patients with cerebrotendinous xanthomatosis and prominent psychiatric symptoms. In three of these patients appropriate diagnosis and treatment were delayed for years because the presence of cerebrotendinous xanthomatosis was not recognized. Early recognition of this potentially lethal disease is important because both the psychiatric and neurological symptoms respond to treatment with chenodeoxycholic acid. PMID- 3344853 TI - Carbamazepine in the treatment of catatonia. AB - Carbamazepine resolved within 6-24 hours the catatonic stupor in two patients, one with a schizophreniform and one with a schizoaffective disorder. Reports of frequent EEG abnormalities and the successful use of diazepam in catatonia prompted these trials with another anticonvulsant. PMID- 3344852 TI - Prolactin, cortisol, and antidepressant treatment. AB - In four depressed patients with abnormal dexamethasone suppression test results before treatment, plasma prolactin levels significantly increased after successful amitriptyline therapy. Such an increase did not take place in five depressed patients with normal dexamethasone suppression test findings. PMID- 3344854 TI - Characteristics of psychiatric consultations in a pediatric cancer center. AB - Data on psychiatric consultations with 58 pediatric cancer patients are summarized. Although most patients received DSM-III axis I diagnoses, adjustment disorder was diagnosed in 30 cases (52%). The patients with primarily depressive features were significantly older than those with anxious features. PMID- 3344855 TI - Obligatory associations: a function of dreaming. AB - Some dream images are unequivocally linked to events experienced in the waking state but are not identical. The author refers to such alterations as "obligatory associations"; these serve varied psychical requirements, including cognitive transformation. PMID- 3344856 TI - Depressive disorders in 100 adolescents who attempted suicide. PMID- 3344857 TI - Alprazolam plus buspirone in treatment of anxiety. PMID- 3344858 TI - Verapamil caused depression, confusion, and impotence. PMID- 3344859 TI - Bromocriptine treatment of cocaine abuse in patients maintained on methadone. PMID- 3344860 TI - Cholinergic mechanisms in delirium. PMID- 3344861 TI - Survivors of childhood experiences in Japanese concentration camps. PMID- 3344862 TI - Conceptual basis of posttraumatic stress disorder. PMID- 3344863 TI - Correct diagnosis for "Alcoholic jealousy" in DSM-III-R. PMID- 3344864 TI - Patients' review of case reports. PMID- 3344865 TI - The observed and the observer. PMID- 3344867 TI - Psychiatric residents' attitudes about the internship: an additional variable. PMID- 3344866 TI - Ethical problem solving. PMID- 3344868 TI - Choice of a residency program. PMID- 3344869 TI - Solvent-inhalant abuse. PMID- 3344871 TI - Dr. know-it-all in movie psychiatry. PMID- 3344870 TI - Phenomenology and family history of affective disorder in Cushing's disease. PMID- 3344873 TI - Further examination of extreme haircutting and psychosis. PMID- 3344872 TI - Too many psychiatrists? PMID- 3344874 TI - Selection of subjects for study of depression in adolescents. PMID- 3344875 TI - A prospective comparison study of double contrast computed tomography (CT) arthrography and arthroscopy of the shoulder. AB - Thirty consecutive patients who underwent double contrast CT arthrography prior to shoulder arthroscopy were prospectively studied. Results from both studies were recorded with the radiologist blinded to the arthroscopic findings when making the final CT reading. The sensitivity, specificity, and accuracy, respectively, of CT arthrography findings compared to arthroscopy were 50%, 100%, 96% for rotator cuff; 66%, 100% 96% for bicipital labral complex; 100%, 100%, 100% for loose bodies; 50%, 100% 93% for Hill-Sachs lesions; 90%, 73%, 83% for anterior labral defects; and 100%, 100%, 100% for posterior labral defects. We conclude that shoulder arthroscopy accurately delineates abnormalities of the anterior and posterior labrum, bicipital labral complex, rotator cuff, joint synovium, and humeral head. CT arthrography accurately delineates capsular redundancy, loose bodies, hardware around joints, and bony glenoid rim abnormalities. PMID- 3344876 TI - Posterior cruciate ligament reconstruction by transfer of the medial gastrocnemius tendon. AB - A retrospective study to determine the efficacy of medial gastrocnemius tendon transfer for symptomatic PCL instability is presented. Results from a group of 31 patients undergoing this procedure were compared with a group of 8 patients managed conservatively while awaiting surgery. The mean injury to follow-up interval was 82 months in the operated group and 104 months in the nonoperated group. The mean surgery to follow-up interval was 53 months. Sixty-nine percent of surgical patients were subjectively improved; however, 29 (91%) continued to have pain and 19 (59%) continued to experience giving way. Thirteen patients from the operated group who had associated procedures performed were significantly better subjectively than those with no associated procedures (P less than 0.05). Physical examination demonstrated no difference in clinical laxity between the operated and nonoperated groups. Medial gastrocnemius transfer did not result in any significant reduction in anterior-posterior translation (KT-1000 assessment) when reconstructed knees were compared with control posterior cruciate deficient knees. Surgery, combined with subsequent immobilization, may have also been responsible for the significant reduction in lower limb function observed in the reconstructed patients. We do not recommend this procedure as a primary PCL reconstruction. PMID- 3344877 TI - Magnetic resonance imaging of the knee. AB - Magnetic resonance imaging (MRI) is an accepted non-invasive modality for evaluation of soft tissue pathology without exposure to ionizing radiation. Current applications demonstrate excellent visualization of the anatomy and pathology of various organs. Preliminary studies in the knee reveal fine resolution of anatomy and pathology involving the meniscus. The purpose of this study is to determine a prospective correlation between MRI scans and actual meniscal pathology as documented at the time of arthroscopy. MRI scans were obtained in 155 patients, on 156 knees (one patient with bilateral scans), with 86 patients (87 knees) eventually undergoing diagnostic and operative videoarthroscopy performed by the same surgeon (DWJ). All images were obtained on the same high-resolution 1.5 Tesla GE Signa Magnetic Resonance Scanner with the same radiologist performing all readings (PEB). The knees were studied in the coronal and sagittal plane using a spin echo sequence and 5 mm slice thicknesses. The menisci were described as having Grade 1, 2, or 3 changes, with Grade 3 reserved for complete tears. Using arthroscopy as the diagnostic standard, the accuracy of MRI in diagnosing medial and lateral meniscal tears was 93.1% and 96.6%, respectively with a Grade 3 MRI reading. For tears of the ACL, the accuracy was 96.6% as confirmed at arthroscopy. Five tears of the PCL were also documented by MRI and correlated with clinical evaluation. Other abnormalities seen were articular cartilage and osteochondral defects, bone tumors, tibial plateau fractures, Baker's cysts, and meniscal cysts. The MRI scan is a highly accurate, noninvasive modality for documentation of meniscal pathology as well as cruciate ligament tears in the knee. PMID- 3344878 TI - The absent posterior drawer test in some acute posterior cruciate ligament tears of the knee. AB - Over a 10 year period, 24 of 54 acute PCL tears in cases of straight medial instability demonstrated an absent or an equivocal posterior drawer test. Most of these (22, 91.6%) were contact injuries, and in the 11 cases where the mechanism of injury was known (45.8%), were incurred by a blow to the outer aspect of the leg while the foot was planted. The ACL was normal in 6 of the 24 knees. The abduction stress test at 0 degree extension was severely positive (2+ or more) in 21 of the 24 knees (87.5%). The phenomenon of an absent or equivocal posterior drawer test in the situation of acute straight medial instability is felt to occur when the mechanism of injury does not stress, strain, or tear the arcuate complex. If the PCL tear is not discovered and repaired, repeated stressful activity stretches the arcuate complex, and the chronically unstable knee subsequently presents with a positive posterior drawer test. PMID- 3344879 TI - Arthroscopic subacromial decompression. An anatomical study. AB - Anterior acromioplasty as described by Neer has been an effective procedure for shoulder impingement syndrome. Recent presentations by Ellman suggest that an effective acromioplasty may be performed arthroscopically. These clinical reports have not been supported by any laboratory experience. The purpose of our study was to examine the feasibility and attempt to quantitate the results of arthroscopic subacromial decompressions. Six acromioplasties were performed according to the recommended technique of Dr. Neer to create a standard for comparison. Fourteen fresh postmortem specimens were studied. In seven shoulders a standard acromioplasty was performed with an osteotome. In seven shoulders an acromioplasty was performed using standard arthroscopic approaches and motorized instruments. In five shoulders an isolated division of the coracoacromial ligament was performed arthroscopically. The coracoacromial ligament was completely divided in all five cases. In the osteotome group adequate bone was resected in 75% (21/28) measured locations. In the arthroscopic group adequate bone was removed at 86% (24/28) location. This difference is not statistically significant. In the cadaver, anterior acromioplasty was performed effectively and predictably with arthroscopic instruments. This compared favorably to a conventional osteotome acromioplasty. It was concluded that coracoacromial ligament division can be accomplished. PMID- 3344880 TI - Concussions in college football. A multivariate analysis. AB - The purpose of this investigation was to examine risk patterns of concussion in college football. Multivariate models were used to interpret the data. Specifically, log-linear modeling and analysis techniques were incorporated into the investigation. An average of 49 college teams were studied over the 8 year period 1975 to 1982. This represented over 36,000 athlete-seasons and 395 team seasons. The data selected were limited to 1,005 game-related concussions. The general hypotheses tested were the null hypothesis that the variables of team (offense and defense), player position, situation (rushing and passing), and activity (block and tackle) had no effect on the occurrence of these game-related concussions. It was found that concussions were a persistent and regular but relatively infrequent type of injury in college football. Concussions accounted for 75% of the total number of injuries on or about the head. The injuries were examined relative to player position, situation, and activity using a log-linear modeling technique, with interactions among the variables also established. The contribution of each variable was not always equal or completely interactive. Generally, the highest risk of concussion was associated with offensive and defensive players involved in a block on a rushing play. Specifically, running backs demonstrated the highest risk of concussion, regardless of activity. The lowest risk was for offensive linemen and quarterbacks while blocking on any type of play. On defense, the secondary exhibited the highest risk of concussion while being blocked on a running play. Similarly, linemen experienced their greatest risk while being blocked on plays run inside the tackle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344881 TI - Study of the infrapatellar nerve. AB - During operations on the knee, such as open meniscectomy and pes anserinus transplant for chronic anteromedial rotatory instability of the knee, the infrapatellar nerve may easily be damaged or severed. Knowledge of the normal anatomical variations of this nerve is thus of importance to the surgeon, so that he can avoid postoperative distress caused by unintentional injury to the infrapatellar nerve. Anatomical variations of this nerve have been studied in 20 cadavers, with particular reference to its relationship to the sartorius and the nerve's distance from the medial femoral epicondyle. In 52.9% of the cadavers studied, the anatomy of the infrapatellar nerve was identical on both sides. Four types of nerve were found and classified according to their relationship to the sartorius: posterior, penetrating, parallel, and anterior. The commonest type was the posterior (62.2%), where the nerve emerged at the posterior border of the sartorius before passing superficial to it to supply the skin and fascia over the front and medial aspect of the knee and the proximal part of the leg. Situated furthest from the medial femoral epicondyle was the parallel type (average, 105.7 mm), which runs parallel to the posterior border of the sartorius before crossing it at infrapatellar level. PMID- 3344882 TI - Stress fractures of the medial malleolus. AB - Six athletes, all engaged in running activities at the time of injury, presented with tenderness over the medial malleolus and ankle effusion. Three patients had a fracture line which could be seen on radiographs. These patients were treated by open reduction and internal fixation using two 4.0 cancellous screws. The other three patients had normal radiographs but bone scans showed increased uptake over the medial malleolus. These patients were treated with cast and immobilization. We believe that each of these patients suffered a stress fracture of the medial malleolus. We suggest that the possibility of a stress fracture be considered in the differential diagnosis of patients who present with 1) chronic or subacute pain over the medial malleolus and ankle effusion, and 2) a history of running activity at the time of injury or running activities aggravating the pain. Bone scans appear to be more sensitive than radiographs in detecting a stress fracture of the medial malleolus. We propose that athletes with radiographic signs of a medial malleolar fracture who desire early return to full participation should be treated by open reduction and internal fixation. For these patients, early motion can be initiated. Other athletes whose fracture cannot be detected on radiographs but whose malleolus shows increased uptake in the area on bone scans can be treated nonsurgically with immobilization and then progressive increase in activity. All of our patients returned to full activity between 6 and 8 weeks after treatment was initiated. PMID- 3344884 TI - The effect of muscle architecture on the biomechanical failure properties of skeletal muscle under passive extension. AB - This study investigates the biomechanical failure properties of five architecturally different skeletal muscles and examines the role muscle structure plays in the passive extension characteristics of musculotendinous units. The muscles used in this study fall into four morphologic categories: fusiform, unipennate, bipennate, and multipennate. Each muscle was pulled to failure at three different rates of strain (1, 10, and 100 cm/min). Specimens of fusiform, unipennate, and bipennate muscles were pulled from their proximal as well as distal attachments. The relationship of elongation to failure of the entire musculotendinous unit to resting muscle fiber length was examined to determine the effect of angle of pennation and fiber length on the failure properties. Our results demonstrate that all four muscle types tested show injury and rupture at the musculotendinous junction whether pulled from proximal or distal attachment, regardless of muscle structure and rate of strain. There was a statistically significant difference (P less than 0.005) in the degree of elongation to failure relative to resting muscle fiber length, with a tendency to greater elongation relative to fiber length for muscles with more pennate structure (tibialis anterior, 72.7% +/- 1.0%; extensor digitorum longus, 113.1% +/- 3.5%; rectus femoris, 225.5% +/- 3.7% elongation in percent resting fiber length). PMID- 3344883 TI - Concentric versus eccentric isokinetic strengthening of the rotator cuff. Objective data versus functional test. AB - Twenty-two male and female college varsity tennis players trained for 6 weeks, one group using eccentric isokinetic internal and external shoulder rotation, and the second group using concentric isokinetic internal and external shoulder rotation. Subjects pretested and posttested both concentrically and eccentrically, so that training overflow and specificity could be examined. Three maximally hit tennis serves made before and after training, which were analyzed by high speed cinematography to obtain ball velocity, served as a functional performance measurement. Statistical analysis of peak torque (newton meters) and peak torque to body weight ratio have revealed significant concentric strength gains (P less than 0.005) in the concentric as well as the eccentric training groups. Eccentric strength gains were demonstrated by the concentric training group at selected speeds (P less than 0.05 and P less than 0.005) but were not generated in the eccentric group at the P less than 0.05 significance level. Functional test analysis shows an increase in maximal serve velocity at a significance level of P less than 0.005 in the concentric training group, with no significant (P greater than 0.01) increases in the eccentric group. PMID- 3344885 TI - Lower trunk brachial plexus compression neuropathy due to cervical rib in young athletes. AB - Compression by a cervical rib may result in neurologic and/or vascular symptoms. Two patients are reported with thoracic outlet syndrome (TOS) secondary to cervical rib. Both patients had vague shoulder pain as well as neurologic manifestations due to compression neuropathy of the lower trunk of the brachial plexus. One patient was suspected initially to have carpal tunnel syndrome. PMID- 3344886 TI - Myositis of the hip in a professional soccer player. A case report. AB - Myositis in the hip joint is a rare entity in sportsmen. Repeated trauma or massage can be detrimental. Successful outcome depends upon the recognition of mature, well-organized new bone, and full excision. Best results can be obtained by performing surgery on a biologically sound joint which contains no trace of active or latent inflammation. The joint should be immobilized till the soft tissue trauma has completely healed. Rehabilitation must be in stages. PMID- 3344888 TI - Pathologic features of allergic bronchopulmonary aspergillosis. AB - We describe the pathologic features in surgically excised lung tissue specimens from 18 cases of allergic bronchopulmonary aspergillosis (ABPA). The main abnormalities involved bronchi and bronchioles. All cases showed bronchocentric granulomatosis (BCG), mucoid impaction of bronchi (MIB), or both. The impacted mucin of MIB contained large numbers of eosinophils and Charcot-Leyden crystals. A distinctive exudative bronchiolitis was present distal to areas of BCG in 13 cases. This lesion was characterized by filling of bronchiolar lumens with necrotic neutrophils and eosinophils in a basophilic mucinous exudate. A peribronchiolar chronic inflammatory infiltrate was seen in 15 cases; eosinophils were prominent in 10 of these cases. Foci of eosinophilic pneumonia were seen in 13 cases, and noninvasive fungal hyphae were identified in 14. We conclude that the finding of BCG or MIB, or a combination of both, especially in conjunction with tissue eosinophilia, should suggest the diagnosis of ABPA. When noninvasive fungal hyphae are also present, the changes are diagnostic of ABPA or a related allergic fungal reaction. PMID- 3344889 TI - Parafollicular C-cells do contain carcinoembryonic antigen. PMID- 3344887 TI - Multicentric angiofollicular lymph node hyperplasia. Pathology of the spleen. AB - Splenomegaly is a frequent clinical finding in multicentric angiofollicular lymph node hyperplasia (MAFH). However, pathologic descriptions of the spleen in MAFH have been reported in only a few cases. The author studied the spleens of seven patients with MAFH (two hyaline-vascular type and five plasma cell type) and reviewed the literature on the pathology of the spleen in this disorder. The histologic features of the seven spleens paralleled those of the lymph nodes. The two hyaline-vascular cases were characterized by white pulp hyperplasia with numerous atrophic and hyaline-vascular germinal centers, and rare plasma cells. In contrast, four plasma cell cases exhibited white pulp hyperplasia with a spectrum of germinal centers ranging from large, hyperplastic centers to typical hyaline-vascular centers, and prominent plasmacytosis. Marked white pulp fibrosis with severe lymphocyte depletion was seen in the fifth plasma cell case, and marginal zone fibrosis with prominent plasmacytosis was seen in one of the other plasma cell cases. The author concludes that the presence of altered germinal centers, white pulp or marginal zone fibrosis, and prominent plasmacytosis should suggest a diagnosis of MAFH in the spleen. PMID- 3344890 TI - Comparison of local, spinal, and general anesthesia for inguinal herniorrhaphy. PMID- 3344891 TI - Nonoperative observation therapy for splenic injuries: a safe therapeutic option? PMID- 3344892 TI - Factors affecting the morbidity of elective liver resection. PMID- 3344893 TI - Forecast of surgical risk in pancreatic cancer. PMID- 3344894 TI - Villous adenoma. PMID- 3344895 TI - Successful localization of parathyroid adenomas by magnetic resonance imaging. AB - Exploration of the neck for primary hyperparathyroidism is facilitated if the parathyroid glands can be localized preoperatively. Magnetic resonance imaging is a noninvasive and relatively safe procedure that is capable of distinguishing and differentiating small soft-tissue structures. Ten patients with primary hyperparathyroidism underwent preoperative diagnostic magnetic resonance imaging followed by cervical exploration. In 9 of these patients (90 percent), imaging correctly predicted the location of a single enlarged parathyroid gland, and in one patient the findings were misleading. All 10 patients proved to have single adenomas in orthotopic locations. Based on this early experience, magnetic resonance imaging appears to be a promising technique for preoperative localization of an enlarged parathyroid gland. PMID- 3344896 TI - Therapeutic options for biliary tract disease in advanced cirrhosis. AB - Between 1979 and 1984, 21 male cirrhotic patients with advanced liver disease, cholecystitis, and jaundice were seen. Eight patients had persistent symptoms of acute cholecystitis despite intense symptoms of acute cholecystitis despite intense medical management. Of these patients, five underwent cholecystostomy and survived. The other three patients had cholecystectomy and one died. Thirteen patients presented with jaundice. Twelve patients underwent endoscopic retrograde cholangiography which revealed gallbladder stones in four but no stones in the common bile duct. They did not undergo further surgical procedures. One patient presented with jaundice, cholangitis, and pancreatitis was found to have stones in the common bile duct and underwent endoscopic sphincterotomy with removal of multiple small, pigmented stones. This patient died from sepsis and renal failure 37 days after sphincterotomy. Endoscopic retrograde cholangiography was unsuccessful in four patients who later underwent percutaneous transhepatic cholangiography which revealed stones in one and cirrhotic ductal changes in three. The remaining jaundiced patient underwent cholecystectomy and common bile duct exploration which revealed no ductal stones. This patient died 21 days after operation from sepsis and multiple organ system failure. Three of five patients with gallstones on endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography died, but none of the deaths were due to biliary tract disease. At last follow-up the two surviving patients were asymptomatic. The overall mortality rate was 14 percent (3 of 21 patients). Cholecystostomy in cirrhotic patients with advanced liver disease and acute cholecystitis is associated with minimal mortality and morbidity. Cirrhotic patients with jaundice are probably best evaluated initially by endoscopic retrograde cholangiopancreatography which is safe, diagnostic, and sometimes therapeutic. PMID- 3344897 TI - Recurrence of colorectal cancer after hepatic resection. AB - Survival estimates of 95, 65, and 49 percent at 1, 3, and 5 years, respectively, after hepatic resection in 77 patients when all gross metastatic cancer was removed compare favorably with the series of Wagner et al [20] of untreated, apparently comparable patients. In the present series, recurrent disease was evident after hepatic resection, most commonly in the lungs; the liver; and locally, in that order. About half of the 45 patients with a second recurrence were operated on, and the recurrence was completely removed in roughly half of these patients. A median survival estimate of 31 months (range 1 to 67 months) after complete removal of the second recurrence was better than the survival estimate of 14 months (range 1 to 18 months) for those in whom the recurrence could not be removed (p less than 0.01). An elevated carcinoembryonic antigen level as the only indicator of recurrence after hepatic resection has proved to be an ominous prognostic sign. PMID- 3344898 TI - Treatment of bowel obstruction after operation for colorectal carcinoma. AB - Operative therapy is beneficial in patients with bowel obstruction after operation for colorectal carcinoma. The cause of the bowel obstruction is more likely to be benign following colorectal carcinoma than following other malignancies. Also, the period of preoperative nasogastric suction can safely be extended to 3 to 4 days in these patients, since a resolution rate of 28 percent can be achieved with minimal risk of strangulation. PMID- 3344899 TI - Negative findings on fine-needle aspiration biopsy of solid breast masses: patient management. AB - A series of 245 fine-needle aspirations of solid breast masses has been reviewed. Seven aspirations were reported as unsatisfactory, 178 revealed benign masses, 7 were indeterminate, and 53 revealed malignancy. Fifty-two of 53 masses diagnosed on aspiration as malignant were confirmed by surgical biopsy (98 percent sensitivity). Open biopsy was carried out on 50 of 178 masses reported as negative on needle biopsy and benign masses were revealed in 46 cases (92 percent specificity). The remaining 128 masses with negative findings were observed and follow-up of 101 patients obtained. Cancer did not develop in any of these patients. Careful physical examination and mammography can predict if a breast mass is malignant or benign in 85 to 90 percent of patients. If fine-needle aspiration biopsy is added and performed by physicians and cytopathologists experienced in the technique, additional information is obtained which allows greater diagnostic accuracy and may eliminate many breast biopsies. PMID- 3344900 TI - Splenectomy for cytopenias associated with systemic lupus erythematosus. AB - Splenectomy was performed in 20 patients with refractory cytopenias associated with systemic lupus erythematosus. An immediate and sustained increase in platelet count (greater than 150,000 cells/mm3) was achieved in 12 of 18 patients whose principal indication for operation was thrombocytopenia. Of seven patients with hemolytic anemia, which was linked with thrombocytopenia in five, six had an increase in the hematocrit value of 20 percent or more after operation. The white blood count increased to normal values in three leukopenic patients. We believe that although removal of the spleen is not uniformly successful in correcting cytopenias in patients with systemic lupus erythematosus, splenectomy should be considered in patients refractory to other modalities of treatment. PMID- 3344901 TI - Operation for hyperthyroidism. Methods and rationale. AB - Five hundred patients with hyperthyroidism underwent operation between 1970 and 1984. Sixty-nine percent had Graves' disease, 19 percent had toxic thyroid adenoma, and 12 percent had multinodular toxic goiter. Good results were achieved in the 275 patients most recently treated. These results may be attributed to the following: good personal contact between the surgeon and the patient at the first meeting, 1 month of preoperative management with carbimazole and propranolol without interruption of work, operation adapted to the type of goiter, and treatment of postoperative tachycardia by propranolol. The mean duration of hospital stay was 5 days. Sequelae were rare. In the patients with Graves' disease, results at 2 years were as follows: 74 percent of operated patients were euthyroid, 23 percent required substitutive treatment, and surgical treatment failed or early relapse occurred in 3 percent. There were no recurrences after operation in patients with solitary or multinodular toxic goiter, but 30 percent of the former and 98 percent of the latter had to be treated with L-thyroxine. Seventy-two percent of the patients who presented with atrial fibrillation had return of normal cardiac rhythm after operation. PMID- 3344902 TI - Surveillance of deep vein thrombosis in asymptomatic total hip replacement patients. Impedance phlebography and fibrinogen scanning versus roentgenographic phlebography. AB - Nine hundred thirty-seven limbs in 537 patients over the age of 39 years who underwent total hip replacement were studied by roentgenographic phlebography, cuff-impedance phlebography, and iodine-125 fibrinogen scanning. Cuff-impedance phlebography had a sensitivity of only 12.3 percent for thigh thrombi. Fibrinogen scanning had a sensitivity of only 59.1 percent for calf thrombi and 13.7 percent for thigh thrombi. The combined use of the two methods resulted in only a 23.2 percent sensitivity for thigh thrombi and an overall sensitivity of 47.4 percent. We have concluded that in asymptomatic patients, in contrast with symptomatic patients, the combination of cuff-impedance phlebography and fibrinogen scanning is not an effective screening method. PMID- 3344903 TI - Acute aortic occlusion. AB - Acute aortic occlusion is a rare and emergent vascular event. Patients who present with this disorder have a classical history and physical examination consistent with occlusion of the distal aorta and resultant ischemia to the distal tissues. Time is of the essence in dealing with these patients. Aortography proved to be important in determining renal artery involvement in our patients. Based on this finding, we suggest that preoperative arteriograms be obtained. The method of treating these patients after arteriography should be to move quickly to the operating room. Patients with renal artery occlusion must be seriously considered for primary revascularization with either aortofemoral or aortoiliac reconstruction and thrombectomy or bypass of the occluded renal artery. If no renal artery involvement is revealed on arteriography, the initial operation should include an attempt to reestablish inflow by retrograde femoral thromboembolectomy under local anesthesia. If that fails, a decision must be made based on the patient's clinical status, whether a major vascular procedure would be tolerated. If so, primary revascularization or transabdominal thrombectomy should be attempted. If the patient is deemed unable to tolerate a major vascular procedure, then axillobifemoral bypass under local anesthesia should be performed. Postoperatively, the patient should be aggressively managed to prevent pulmonary and renal complications. Even with aggressive surgical management and postoperative care, these patients have an uncertain postoperative course. It is of primary importance that physicians realize that time is a critical factor and these patients must be referred to the appropriate care center promptly. Only by ensuring prompt surgical management can a mortality rate of less than 50 percent be expected. PMID- 3344904 TI - Cholecystectomy in the elderly. AB - A series of 347 elderly patients undergoing cholecystectomy has been presented. The older a patient is at the time of cholecystectomy, the more likely it is for that patient to present with an acute biliary complication. The elderly tolerate biliary tract operations quite well, especially before acute complications of cholelithiasis occur. Early cholecystectomy can prevent the morbidity associated with the natural progression of cholelithiasis. Whether prophylactic cholecystectomy for asymptomatic cholelithiasis would be cost effective is an issue that can be resolved only when further data regarding the natural history and incidence of cholelithiasis in the elderly is known. PMID- 3344905 TI - Endoscopic closure of bronchopleural fistulas using a tissue adhesive. AB - Bucrylate tissue adhesive has been found to be effective in achieving closure of surgically created bronchopleural fistulas in dogs. Success was obtained with both endoscopic and direct application. Clinical application of this method in one patient was successful [unpublished observations]. We believe that the speed, low risk, and cost-effectiveness of this approach justifies its further use in these difficult situations. PMID- 3344906 TI - Modified technique of sphincteroplasty with the use of a specially prepared cannula. AB - A modified technique of sphincteroplasty with the use of a specially prepared cannula can exclude the pancreatic duct from the operative field by covering it with the posterior wall of the cannula. The use of the cannula can avoid some of the technical difficulties that may be encountered with operations involving the papilla of Vater. Our experience with 51 patients has been presented. PMID- 3344907 TI - Trends in the surgical management of duodenal ulcer. A fifteen year study. AB - The number of patients undergoing definitive duodenal ulcer operation at Charlotte Memorial Hospital and Medical Center declined by 75 percent from 1971 to 1985. The percentage of women making up the total study population increased to 40 percent in the period from 1981 through 1985. Average patient age also increased. Fewer gastric resections are now being performed and emergency operations are becoming more frequent, with bleeding being the most common indication. Splenic lacerations requiring splenectomy in patients undergoing vagotomy occurred in 3.1 percent of the study population during the 15 year study. The overall mortality rate for elective operations was 1.5 percent and for emergency operations, 17.2 percent. The incidence of acute duodenal ulcer perforation increased during this 15 year study. Duodenal ulcer operations have changed in number and in type as the manifestations of the disease have become altered by trends that began in the mid 1950s and became exaggerated by more effective ulcer therapy. PMID- 3344908 TI - Gastric disconnection in the management of perforated giant duodenal ulcer. AB - Giant duodenal ulcer is the most severe variant of peptic ulcer disease. Currently, however, no technical recommendations exist for the surgical management of perforation of these lesions. Due to the often extensive loss of duodenal substance, plication is impossible, pyloroplasty is hazardous, and duodenal closure is tenuous at best. In the absence of surgical precedent, it was thought that an ideal procedure would embody three principles: (1) defunctionalization of the upper gastrointestinal tract; (2) minimization of suture lines; and (3) control of potential fistula sites with tube enterostomies. As it finally evolved, the procedure of gastric disconnection became truncal vagectomy and antrectomy, along with tube gastrostomy, duodenostomy, and jejunostomy. Restoration of gastrointestinal continuity was deferred for 3 to 4 weeks after recovery. Four consecutive patients have been successfully managed by this technique. Gastric disconnection is physiologically sound and may prove to be superior to alternative techniques in this difficult condition. PMID- 3344910 TI - Gastrointestinal perforation in infants. AB - We found that the mortality rate was no greater in patients with necrotizing enterocolitis complicated by perforation compared with the rate in those with other causes of perforation in similar weight classes. Iatrogenic injuries had a 50 percent mortality rate in all gestational age and birth weight categories and, therefore, great caution and surveillance are of utmost importance when using invasive monitoring and therapeutic modalities to prevent this cause of perforation. Term infants had a preponderance of mechanical causes of perforation which mainly occurred in the foregut and proximal midgut, whereas premature infants have a preponderance of asphyxial or ischemic events underlying perforations which mainly occurred in the ileocolic region and were often associated with necrotizing enterocolitis. Although neonatal intestinal perforation is a catastrophic event, the very premature infant weighing less than 1,000 g at birth is at significantly greatest risk. The discouraging 20 percent survival rate in the less than 1,000 g premature infants presents a challenge to the surgeon, since the overall survival rate was 59 percent and the term infants had a 78 percent survival rate. A substantial share of the mortality in the infants weighing less than 1,000 g at birth relates to the occurrence of intracerebral hemorrhage and bronchopulmonary dysplasia. Vigorous medical and surgical approaches can be used to salvage premature infants in all weight classes with gastrointestinal perforation. PMID- 3344909 TI - A prospective, randomized study comparing highly selective vagotomy and extended highly selective vagotomy in patients with duodenal ulcer. AB - The recurrence rate of duodenal ulcer after highly selective vagotomy is nearly 10 percent. To diminish this percentage, extended highly selective vagotomy with sectioning the gastroepiploic nerves has been proposed in order to reduce postoperative gastric acid secretion. We have prospectively compared the decrease in gastric acid secretion through measurement of basal acid output, maximal acid output, and peak acid output in patients who underwent highly selective vagotomy or extended highly selective vagotomy. No significant differences in postoperative gastric acid secretion were found and, therefore, no changes in the probability of postoperative recurrence of duodenal ulcer were seen. PMID- 3344911 TI - Value of contrast-enhanced computerized tomography in the early diagnosis and prognosis of acute pancreatitis. A prospective study of 202 patients. AB - Two hundred two patients admitted with the clinical suspicion of acute pancreatitis underwent computerized tomography scanning within 36 hours of admission. The diagnostic value of the computerized tomography findings was excellent, with a sensitivity of 92 percent and a specificity of 100 percent. One hundred seventy-six patients with acute pancreatitis defined according to the overall clinical course were included in the prognostic study. The pancreatitis was fatal in 21 patients, severe in 47 patients, and mild in 108 patients. The computerized tomography findings were classified into the following three groups on the basis of the extent of phlegmonous extrapancreatic spread: Group I, no phlegmonous extrapancreatic spread (100 patients, none died); Group II, phlegmonous extrapancreatic spread in one or two areas (28 patients, mortality rate 4 percent); and Group III, phlegmonous extrapancreatic spread in three or more areas (48 patients, mortality rate 42 percent) (p less than 0.0001). The following three scores from prognostic clinical and laboratory data were also obtained: Score 1, zero or one positive sign (82 patients, none died); Score 2, two to four positive signs (54 patients, mortality rate 13 percent); Score 3, five or more positive signs (40 patients, mortality rate 35 percent) (p less than 0.001). The combination of computerized tomography findings and prognostic signs had the best predictive value. Patients in Group III, Score 3 (24 patients) or Group III, Score 2 (19 patients) had mortality rates of 58 percent and 32 percent, respectively, and complications developed in all of the survivors. In addition, all except two acute pancreatitis patients in whom pancreatic abscess developed were found in Group III (p less than 0.0001). Furthermore, for Group III patients, the prediction of death associated with abscesses was enhanced by the number of prognostic signs. The mortality rate increased from 17 percent for Score 2 patients to 81 percent for Score 3 patients (p = 0.0078). As a result of this study, we recommend early computerized tomography for all Score 2 and Score 3 patients, since it allows prompt recognition of patients at high risk for systemic and local complications. Adequate therapy can then be directed to the group of patients to whom it is best suited. Serial computerized tomographies should be reserved for those patients presenting with phlegmonous extrapancreatic spread. PMID- 3344912 TI - Adenocarcinoma of the appendix. AB - Thirty-two patients with primary adenocarcinoma of the appendix were studied in this collective review. Immediate operation was performed in 21 patients with a diagnosis of acute appendicitis. At operation, tumor of the appendix was only identified in 50 percent of the 32 patients studied. Survival was unrelated to the histologic tumor type, but significantly correlated with the extent of tumor spread. Right hemicolectomy led to a significant increase in survival compared with appendectomy alone and to a significant decrease in risk of recurrence. In Dukes' B2 and C patients, differences in the survival curves were in favor of right hemicolectomy. Long-term survival was obtained by repeat laparotomy with resection of mucinous material in patients with pseudomyxoma peritonei. PMID- 3344913 TI - Lymphadenectomy for cure in patients with early gastric cancer and lymph node metastasis. AB - The anatomic distribution, size, and histologic mode of involvement of 98 metastatic lymph nodes in 49 of 370 patients were examined to determine to what extent lymphadenectomy should be performed in addition to gastrectomy in patients with early gastric cancer. Nodal involvement in the marginal sinus (30 nodes) and partial medullary sinus (37 nodes) were commonly seen, and the lymph nodes of those types were enlarged compared with 1,086 patients with no metastatic lymph nodes (control group). Lymph nodes of the wide medullary sinus (11 nodes), small nodule (3 nodes), and massive involvement types (17 nodes) did not enlarge compared with those of the other types and those of the control group. Most of the metastatic sites (76.6 percent) were in the perigastric lymph nodes along the lesser and greater curvatures, about a fifth were in the extraperigastric nodes along the left gastric, common hepatic, celiac, and splenic arteries, and the least were in the extraperigastric nodes (3.1 percent) along the hepatoduodenal ligament. Since the rate of macroscopic diagnosis during operation was so poor, regardless of the histologic modes of nodal involvement, and also in cases of metastatic lymph nodes less than 15 mm in widest diameter, for curative operation of patients with early gastric cancer, perigastric and extraperigastric lymph nodes along the main arteries near the stomach should be completely dissected, in addition to resection of the stomach. PMID- 3344914 TI - Carcinoma of the cardia and proximal third of the stomach. Results of surgical treatment in 91 consecutive patients. AB - In the present retrospective study, 79 percent of the patients were men with a median age of 65.5 years. Of 91 patients, 84 were surgically explored. Excision of the tumor was carried out in 57 patients (63 percent) and was curative in 28 cases and palliative in 29 cases. Curative resection included proximal gastrectomy in 5 patients and total gastrectomy in 23 patients, which was extended to the spleen and distal pancreas in 18 patients. Lymph node metastases were found in 67 percent of the patients treated by resection. According to the TNM classification, 18 percent of the patients undergoing resection had stage I tumor, 28 percent had stage II tumor, 40 percent had stage III tumor, and 14 percent had stage IV tumor. The postoperative mortality rate was 16 percent for the entire series, 21 percent for patients undergoing palliative resection, and only 4 percent for patients undergoing curative resection. Three patients had an obvious anastomotic leak, one of whom died. Median survival time was 5 months for patients who had exploration only, 6 months for patients who had palliative resection, and 36 months for patients who had potentially curative resection. The 5 year actuarial survival rate was 20 percent for patients having resection and 40 percent for patients having curative resection. Survival was closely related to tumor stage. These results indicate that total gastrectomy with complete abdominal lymph node dissection can give comparatively good long-term results when performed for cure. Nevertheless, only one of three patients in this series could have a potentially curative resection. The only way to increase the curative resection rate and to improve survival is to detect the cancer at an early stage. PMID- 3344915 TI - Near-total gastrectomy for gastric cancer. AB - Fifty-nine consecutive patients (95 percent) with gastric cancer of the distal portion of the stomach were operated on with 95 percent subtotal gastrectomy between 1975 and 1980. The operations were for cure in all cases. Twenty-five patients were alive after 5 years, for a crude 5 year survival rate of 42 percent. The operative mortality rate was 5 percent (three patients). Twenty-four patients (41 percent) had complications, which consisted of postoperative respiratory infection in 11 patients (19 percent), postoperative ileus in 4 patients (7 percent), and subphrenic abscess in 2 patients (3.4 percent). In addition, there was one wound dehiscence and one liver rupture (with fatal outcome), one deep venous thrombosis, one urinary infection, and one wound infection. Only one patient (1.7 percent) had an anastomotic leak at the gastrojejunostomy site. Seven relaparotomies (12 percent) had to be performed for complications. We have concluded that, in patients with distal gastric cancer, 95 percent subtotal gastrectomy can result in a 5 year survival rate that is comparable to that reported in the literature for total gastrectomy, and it has the advantage of a very low rate of anastomotic leakage between the minute gastric remnant and the jejunum. Therefore, 95 percent subtotal gastrectomy is recommended over total gastrectomy in the treatment of distal gastric cancer. PMID- 3344917 TI - Limitations and dangers of gastrografin swallow after esophageal and upper gastric operations. AB - In a series of 135 patients who underwent esophageal and upper stomach surgery, the incidence of anastomotic leakage was 20.4 percent. One hundred four patients had either Gastrografin swallow or the methylene blue test to evaluate anastomotic integrity before resumption of oral feeding. Both tests were disappointing in that methylene blue failed to detect any case of leakage and Gastrografin swallow could only detect three cases of subclinical leakage. The high false-negative detection rate of Gastrografin swallow might be related to the inferior radiographic detail provided by this contrast medium. Aspiration of Gastrografin is potentially dangerous and could be fatal. We believe that barium sulfate, which provides better radiographic detail and is not so hazardous when aspirated, should be the contrast medium of choice. PMID- 3344916 TI - Roux-Y stasis syndrome after gastrectomy. AB - The aim of the present study was to determine which factors lead to upper gastrointestinal stasis after Roux-Y reconstruction. Among the 214 patients with Roux-Y reconstructions performed between 1961 and 1983, follow-up data were obtained for 187 (87 percent) after a mean of 6.2 years. Patients with vomiting of food but not bile, postprandial pain, and nausea were considered to have the Roux-Y stasis syndrome. The syndrome was found in 49 patients with gastrojejunostomy (30 percent of those at risk) but in only 2 patients with esophagojejunostomy (8 percent, p less than 0.05). The condition was more common in women than men (p less than 0.05), but it was equally common in patients with and without vagotomy. The mean length of the Roux-Y limb in patients with stasis was 41 cm, which was longer than the 36 cm in patients without stasis (p less than 0.001). When multiple logistic regression was used, the length of the Roux-Y limb emerged as the major risk factor (p less than 0.01). In conclusion, construction of Roux-Y limbs greater than about 40 cm in length may increase the incidence of the Roux-Y stasis syndrome. PMID- 3344918 TI - Colonic interposition for benign esophageal disease. Long-term clinical and endoscopic results. AB - Replacement of the esophagus for benign disease requires familiarity with the long-term results of various esophageal substitutes. In the present study, 60 esophageal reconstructions for benign disease using colonic interposition have been presented. The operations were performed mainly without thoracotomy, using both antiperistaltic and isoperistaltic colonic segments. There were no differences in swallowing ability between patients with antiperistaltic and patients with isoperistaltic interpositions. Regurgitation symptoms, however, seemed to be somewhat more common and more difficult in patients with antiperistaltic colonic transpositions. Endoscopic signs of colitis were common, but they did not correlate with regurgitation symptoms. Bacterial cultures from the transplanted colon mainly revealed the usual mouth organisms. Candida albicans was frequently found in the fungal samples. There were no differences in the results between patients with follow-up periods of more and less than 2 years. The clinical results were good or fair in a great majority of the patients. PMID- 3344919 TI - Computerized ambulatory esophageal pH monitoring in 50 asymptomatic volunteer subjects. Results and clinical implications. AB - Fifty asymptomatic volunteer subjects underwent prolonged computerized ambulatory distal esophageal pH monitoring to characterize acid reflux patterns. A bimodal distribution of data, which corresponded to the erect and supine positions, occurred in 45 subjects, and separate mean baseline pH values were noted for the erect and supine positions (pH 6.46 and pH 5.46, respectively, p less than 0.001). At esophageal pH 4, reflux episodes occurred more commonly in the erect position (44 percent) than in the supine position (20 percent). There were also significantly greater numbers of reflux events and longer durations when the pH was below 3 (p less than 0.02) and 4 (p less than 0.001) in the erect compared with the supine position, but prolonged events (more than 10 minutes) occurred in both positions. Postprandial reflux occurred in 78.7 percent of the subjects, with an average of 5.1 episodes. A slight but significant correlation between age and erect reflux was seen (p less than 0.04). In the pH 3 to 5 range, 18 percent of the subjects had acid exposure in excess of the group mean plus 2 standard deviations and 10 percent in excess of the mean plus 3 standard deviations. Overall, a nonnormal distribution of pH data was found with 28 subjects having less than 1.6 percent of their values below pH 4. This finding may represent either the true spectrum of normal acid reflux or a subclinical pathologic state that will become symptomatic over time. PMID- 3344920 TI - Vertical banded gastroplasty as an antireflux procedure. AB - Vertical banded gastroplasty creates a channel by two applications of the TA-90 stapler from an end-to-end anastomosis window above the crow's foot to the angle of His, against a 32 F. tube along the lesser curvature. The caudad end of the channel is restricted by a 5 cm collar. Thirty-one obese patients more than 45 kg overweight were studied by interview, barium swallow, endoscopy, and manometry. These procedures were repeated 13 +/- 5.5 weeks postoperatively, after resolution of operative edema and before extensive weight loss. Preoperative symptoms included heartburn in 24 patients, regurgitation in 17 patients, and aspiration in 2 patients, and barium swallow demonstrated hiatal hernia in 7 patients and reflux in 7 patients (5 with hiatal hernia). In addition, endoscopy detected mild esophagitis in 3 patients, and hiatal hernia in 11 patients. Postoperatively, the incidence of heartburn decreased in all patients, barium swallow showed slow channel emptying but no hiatal hernia or reflux, and endoscopy did not identify any esophagitis. Preoperative lower esophageal sphincter pressure was 14.5 +/- 7.2 mm Hg. Postoperatively, the vertical banded gastroplasty channel had an initial peak (collar) pressure of 19.2 +/- 7.8 mm Hg (p less than 0.01 compared with preoperative lower esophageal sphincter pressure), a channel pressure of 9.5 +/- 6 mm Hg, a lower esophageal sphincter pressure of 20.1 +/- 7.7 mm Hg (p less than 0.005), and a channel length of 6.8 +/- 1.4 cm. Vertical banded gastroplasty creates a high pressure channel, inhibiting reflux of gastric juice without the need for any additional procedure. PMID- 3344921 TI - Long-term prognosis of patients with severe radiation enteritis. AB - One hundred thirty-six patients (median age 59 years) presented with intestinal complications of previous radiotherapy. Seventy-eight had bleeding or stricture and 58 had perforation or fistula. One hundred twenty-four patients survived for more than 3 months and were followed for a median of 4.5 years. Sixty-eight patients were free of symptoms, whereas 16 experienced operation-related complications. Twelve patients had continuing symptoms of radiation enteritis, and new radiation-induced complications developed in 28. Sixteen of 51 patients with perforation or fistula had new complications compared with 12 of 73 patients with bleeding of stricture (p = 0.05). Overall, 57 patients died during the study. Thirteen died from radiation-induced complications and 27, from recurrent malignancy. Radiation deaths occurred in the postoperative period but had no impact on long-term survival. Life expectancy was poorer in patients presenting with perforation or fistula compared with bleeding or stricture, the main reason being significantly more recurrences among patients with fistulas (p less than 0.05). PMID- 3344922 TI - Intraoperative hemostasis and wound healing in intestinal anastomoses using the ILA stapling device. AB - Intraoperative hemostasis and wound healing of 24 side-to-side intestinal anastomoses constructed with the ILA stapling device were studied in 12 dogs by comparing the ILA-32 and ILA-52 staple cartridges. Hemostasis was evaluated by intraoperative measurement of blood loss and bleeding time at the staple line. There was no statistically significant difference in mean blood loss (p greater than 0.05) or mean bleeding time (p greater than 0.10) between the two cartridges. Wound healing was studied using bursting strength measurements and silicone rubber casting of the microvasculature at the staple line. At 3 days, 1 week, and 2 weeks postoperatively, there was no significant difference between bursting strength values achieved with the two cartridges. Microscopic examination revealed that wound healing in the ILA-52 anastomoses lagged behind healing in the ILA-32 anastomoses at each postoperative time period studied. The silicone rubber casting study showed a paucity of microvasculature at the healing staple line with the ILA-52 cartridge as compared with the ILA-32 cartridge. Our findings suggest that the ILA-52 cartridge does not offer significantly improved intraoperative hemostasis over the ILA-32 cartridge and may affect the microvasculature at the staple line in a way that delays wound healing. PMID- 3344923 TI - Traditional Chinese medicine and Western medicine: a Westerner's view. PMID- 3344925 TI - Traditional Chinese medicine and Western medicine. PMID- 3344924 TI - Induction of osteogenesis by Meckel's cartilage xenografts. PMID- 3344926 TI - Porous hip implants. An alternative to cemented hip replacement. PMID- 3344927 TI - Bilateral aneurysms of the extracranial internal carotid artery. PMID- 3344928 TI - Relevance of chemotherapy in gastrointestinal cancer. PMID- 3344929 TI - Hepatitis vaccination 1987. PMID- 3344930 TI - University of Alabama School of Medicine. Policy on impaired students and faculty with special reference to substance abuse. PMID- 3344931 TI - Development of atopic disease after early administration of cow milk formula. AB - We prospectively studied the incidence of atopic disease in healthy term infants with a birth weight between -1 and -2 SD who were fed a cow milk formula during the first few days of life. A total of 216 infants were randomized to receive either early feeding with formula before normal breastfeeding was started (n = 112) or "normal feeding" with breastmilk (n = 104). Symptoms of allergy developed in 18% of the infants before 18 months of age in the formula fed group, as compared to 33% in the breastfed group (P less than 0.05). The difference was confined to the group of infants with a history of allergy in two family members. Thus, 11% of the formula-fed infants developed allergy symptoms, as compared to 61% of the control infants (P less than 0.01). Our study implies that early feeding during the first days of life with a cow milk formula, before the introduction of breastmilk, may reduce the incidence of allergy symptoms before 18 months of age in infants with a family history of allergy. PMID- 3344932 TI - Down-regulation of natural killer cell activity by autologous polymorphonuclear leucocytes. Role of indomethacin. AB - It has been recently reported that neutrophils are involved in the regulation of NK cell activity. However, the mechanism of such regulation is unclear. The present study was designed to investigate the mechanisms involved in the regulation of NK cytotoxicity by human neutrophils. The role of indomethacin, an anti-inflammatory drug, in this interaction was studied. NK cells were purified from peripheral blood obtained from normal individuals. NK cell cytotoxicity was tested on K 562 cell line by Cr release assay. Autologous neutrophils obtained from peripheral blood were stimulated by opsonized zymosan either in the presence or absence of indomethacin. The role of neutrophil supernatant containing oxygen radicals and prostaglandins on NK cytotoxicity was examined. It was shown that supernatants from stimulated neutrophils significantly inhibited (P less than 0.05) the autologous NK cell cytotoxicity. The presence of indomethacin in the in vitro reaction mixture, or given orally to donors, partially or completely abolished the inhibitory effect of neutrophil supernatant. Indomethacin inhibited prostaglandin E2 release, and luminol-enhanced, myeloperoxidase-mediated chemiluminescence of activated PMN. Diafiltration of neutrophil supernatant showed that the inhibitory activity was present in the fraction containing molecules lower than 5,000 daltons. In conclusion, our findings indicate that down-regulation of NK cytotoxicity is mediated by prostaglandins produced by stimulated neutrophils and possibly by oxygen radicals. PMID- 3344934 TI - Allergy to rabbits. II. Identification and characterization of a major rabbit allergen. AB - Quantitative immunoelectrophoretic techniques have been used to study the antigenic components found in extracts of dust collected from rabbit housing areas. To determine the possible source of these antigens, comparisons have been made to rabbit saliva, urine, fur and dander. Specific antisera for the rabbit extracts were raised in guinea pigs. One major component of the dust (Ag Rl) was also found in large amounts in saliva, slightly less in fur and in only minimal amounts in urine and dander. Crossed radioimmunoelectrophoresis (XRIE) of the dust, performed with sera from 14 rabbit allergic individuals who were RAST positive to rabbit saliva, urine and dust identified four IgE-binding constituents. Individual responses varied but all sera reacted with Ag Rl, identifying this as a major rabbit allergen. Dust RAST inhibition studies with rabbit dust, saliva and urine indicated saliva to be closely related to the dust. Ag Rl is a glycoprotein which appears to be very heterogeneous in nature. It produced a broad biphasic precipitin peak on immunoelectrophoresis and eluted from Sephacryl S-200 gel filtration over the molecular weight range 30-50 Kd, although a molecular weight of 17 Kd was indicated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and gradient gel electrophoresis. The RAST inhibition results and the antigenic similarity of saliva to the dust suggest this to be the most likely source of the major rabbit allergen, Ag Rl. PMID- 3344933 TI - High-dose local steroid treatment in bronchopulmonary aspergillosis. A pilot study. AB - Two patients with allergic bronchopulmonary aspergillosis (ABPA) have been treated with a high dose (1600 micrograms daily) of inhaled corticosteroid for 18 months. A beneficial effect with regard to asthmatic symptoms was observed in both patients. During the first 14 months of the observation period no significant changes were observed in lung function parameters. Bronchial histamine challenge showed decreased hyperreactivity. IgE decreased in both patients, while specific IgE and IgG remained the same. After 14 months of treatment one of the patients developed severe, acute exacerbation of the ABPA and was treated with high-dose prednisolone and local steroid. The patient is now fully recovered and has continued on local steroid therapy. The other patient had no episodes of exacerbation and remains stable on this treatment. PMID- 3344935 TI - Purification and molecular weight studies on the components of a Parietaria pollen extract. AB - The pollen extract of the allergenic plant Parietaria judaica, growing throughout the Mediterranean region, has been purified by high performance liquid chromatography (HPLC) operating in size-exclusion followed by ion exchange. Molecular weight determination of the components and isoelectrofocusing studies on the enriched material have been performed. PMID- 3344936 TI - Diagnosis and immunotherapy of mould allergy. VII. IgG subclass response and relation to the clinical efficacy of immunotherapy with Cladosporium. AB - The IgG subclass response was evaluated by a sensitive allergen- and subclass specific solid phase immunoradiometric assay during a 1-year placebo-controlled, double-blind study of immunotherapy with Cladosporium herbarum in 22 adult asthmatics. The IgG response was mainly restricted to subclasses 1 and 4 but a few patients were IgG2 and IgG3 responders. An intense and early IgG1 response was observed during the first clusters of injection followed by a levelling down of the titer. The IgG4 response had a later onset and showed slowly increasing levels during the 12 months of immunotherapy. The graded clinical efficacy estimated by symptom-medication score was significantly correlated to the preseasonal IgG1 value, with high values indicating a deleterious response of immunotherapy (deterioration of disease activity). Likewise, the fold increase of IgG1 and IgG4 after two clusters of immunotherapy (i.e. after 4 weeks) was significantly related to the clinical outcome. Little or no increase of IgG1 and IgG4 was associated with improvement, i.e. decrease in symptom-medication score. The magnitude of the IgG1 response during the dose-increase phase was directly correlated to the number of systemic side effects. No relation of IgG1, IgG4 or IgG4/IgG1 ratio to changes in the IgE-mediated parameters (skin prick test, bronchial challenge and circulating specific IgE) was observed. Our data, which are based on few patients and only one allergen system, do not support the hypothesis of IgG acting as blocking antibody being the immunologic mechanism of immunotherapy. The association between high IgG4 values and a deleterious efficacy of immunotherapy might be caused by IgG4 acting as sensitizing antibodies. This explanation, however, is opposed by the lack of relation to systemic side effects. PMID- 3344937 TI - Severe anaphylactoid reaction to nalidixic acid. AB - We present the case of a 58-year-old non-atopic woman who suffered an adverse reaction to orally administered nalidixic acid, which had been prescribed for the treatment of a urinary tract infection. The single-blind oral provocation test was positive; the patient presented the clinical features of an anaphylactoid reaction 3 min after administration of nalidixic acid. Both the skin test and the histamine release test were negative. These results suggest that we are dealing with an anaphylactoid reaction not described before with this drug. PMID- 3344938 TI - Allergic alveolitis and late asthmatic reaction due to molds in the tobacco industry. PMID- 3344939 TI - Plasma concentrations of bupivacaine during extradural anaesthesia for caesarean section. The effect of adrenaline. AB - The clinical effects and plasma levels associated with the use of 0.5% bupivacaine with and without the addition of 1:200,000 adrenaline (5 micrograms/ml) were studied in 30 patients who underwent extradural anaesthesia for elective Caesarean section. The addition of adrenaline to bupivacaine prolongs analgesia, reduces the degree of hypotension and delays its onset. Plasma bupivacaine levels were consistently lower when adrenaline was added, but this difference was significant only at 10 minutes after the initial dose. Prolonging the interval between increments seems to be a more reliable way to reduce plasma concentration than the addition of the catecholamine. PMID- 3344940 TI - Respiratory disturbance during recovery from etomidate anaesthesia. AB - A case is described in which recovery from the administration of a single dose of etomidate was complicated by periodic episodes of unconsciousness, tremor and apnoea. Subsequent investigations did not reveal any evidence of neurological disease. PMID- 3344941 TI - Fibreoptic intubation in Klippel-Feil syndrome. AB - A patient with Klippel-Feil syndrome who underwent abdominal surgery is presented and the anomaly reviewed. The anatomical abnormality and potentially unstable neck provide a potentially difficult tracheal intubation which was undertaken using an awake fibreoptic technique. The role of the fiberscope and the advantage of pre-operative assessment of the difficult airway are discussed. PMID- 3344943 TI - Isoflurane and primary pulmonary hypertension. AB - Primary pulmonary hypertension is a rare and fatal disease. These patients represent an anaesthetic challenge because of the high mortality associated with the marked intra-operative increase in pulmonary vascular resistance and right ventricular decompensation. This is a first case report which demonstrates the safe and beneficial effects of isoflurane in lowering pulmonary arterial pressure and pulmonary vascular resistance in such a patient for a short surgical procedure. The anaesthetic considerations in these patients are discussed. PMID- 3344942 TI - Halothane and isoflurane in outpatient anaesthesia. A comparison of recovery. AB - The speed and quality of recovery after anaesthesia were studied in 60 outpatients. Anaesthesia was induced using propofol and maintained by nitrous oxide in oxygen supplemented with either halothane or isoflurane. Initial clinical recovery was significantly faster in the halothane group but no differences were found during subsequent psychomotor testing. Minor postoperative side effects were common in both groups. PMID- 3344945 TI - An evaluation of the Stihler 1FT 200 blood warmer. AB - The performance of the Stihler 1FT 200 blood warmer was evaluated at flow rates from 25 to 150 ml/minute and compared with that of the Hetotherm and Fenwal warmers. The Fenwal proved to be an efficient apparatus at all flow rates but the performance of the Hetotherm fell off slightly at higher flow rates. The Stihler 1FT 200 did not meet requirements for use in the operating room. PMID- 3344944 TI - The oesophageal detector device. Assessment of a new method to distinguish oesophageal from tracheal intubation. AB - A new method to distinguish oesophageal from tracheal intubation using the oesophageal detector device was evaluated. In 100 healthy adults, observers of differing experience reliably and rapidly detected 51 oesophageal and 49 tracheal intubations in a randomised, single-blind trial. In one case, blockage of the tracheal tube was detected swiftly and allowed corrective steps to be taken. This method can be used in patients with bronchospasm to detect correct tracheal placement when auscultation and decreased compliance of the chest may make clinical confirmation difficult. It can be concluded from this study that the oesophageal detector device is a reliable, rapid, inexpensive and easy to use method for the detection of oesophageal intubation and its very low cost should make it readily available in all situations where tracheal intubation is carried out. PMID- 3344946 TI - Pressure infusor devices. Do they generate the pressures indicated? AB - Three currently available pressure infusor devices, based on three different principles, were tested to see if the pressure reading on the infusor manometer corresponds to the pressure generated in the infusion system. Each device was tested in two ways. First, the pressure generated in the infusion system was measured when the infusor bag pressure was maintained at 300 mmHg while the infusion bag was emptied in aliquots of 50 ml. Second, the pressures in the infusor bag required to maintain a pressure of 300 mmHg were measured as the infusion bag was emptied stepwise. The results reveal surprisingly large discrepancies between the pressure registered on the infusor manometer and the actual pressure generated in the fluid, which are not due to manometer inaccuracy. The degree of discrepancy depends on the amount of fluid that remains in the infusion bag and, when the infusor manometer shows a pressure of 300 mmHg, pressure in the fluid can be as much as 170 mmHg above or 200 mmHg below this value. Furthermore, it was impossible to maintain a pressure of 300 mmHg in the infusion system using one of the devices despite the fact that 100 ml fluid remained. The clinical significance of these findings is discussed. PMID- 3344947 TI - Isoflurane as an alternative to halothane for caesarean section. AB - Two series of 25 patients who underwent elective Caesarean section with general anaesthesia were given either 0.75% isoflurane or 0.5% halothane as supplements to 50% nitrous oxide in oxygen used for maintenance. The potent inhalational agent was given for the entire operative period and no case of intra-operative dreaming or awareness was reported. The infusion dose of suxamethonium was significantly less with isoflurane, 50 micrograms/kg/minute (SD 17), as compared to halothane, 64 micrograms/kg/minute (SD 24) (p less than 0.02). Recovery from anaesthesia was more rapid with isoflurane. The surgeon's assessment of uterine relaxation and bleeding using a visual analogue score indicated that this was significantly less with isoflurane. Infant well-being as judged by Apgar score and cord blood gas analysis, showed little difference between the two inhalational agents. PMID- 3344948 TI - Hypoxaemia after premedication in cardiac patients. Glycopyrronium compared with hyoscine. AB - Arterial blood gases were analysed before and approximately one hour after premedication in two groups of 10 patients awaiting cardiac surgery. One group received intramuscular papaveretum and hyoscine, the other papaveretum and glycopyrronium. Similar, small but statistically significant reductions in mean arterial oxygen tension and oxygen saturation, and increases of arterial carbon dioxide tension occurred in both groups. Hypoxaemia in individual patients was unpredictable and in some was clinically relevant. PMID- 3344949 TI - Survey of the practice of epidural analgesia in a regional sample of obstetric units. AB - An investigation into practices of the epidural services in a regional sample of obstetric units was undertaken following recent reported disasters associated with epidural analgesia for labour pain. A questionnaire was completed by all 22 obstetric units in the region, which included six teaching, 14 district and two independent centres. In three units the epidural service was shared with the obstetricians. A continuous anaesthetic presence was provided in 16 of 22 units. There was considerable variation in the attendance upon epidural patients by the anaesthetists. Instructions to midwives for top-ups and subsequent care of patients followed no uniform pattern. Midwife in-service training in the initial management of serious epidural complications and in cardiopulmonary resuscitation was inconsistent. In some units, the avoidance of aortocaval compression was not emphasised in the management of serious complications such as severe maternal hypotension, total spinal blockade or cardiac arrest of the parturient. The results obtained in this survey suggest that there is a need to review the requirements in the provision of obstetric epidural services and consideration should be given to the establishment of a generally accepted standard of practice. PMID- 3344951 TI - Postoperative laryngospasm triggered by acute angina? PMID- 3344950 TI - General anaesthesia in minor surgery and myocardial infarction. PMID- 3344952 TI - Hypersensitive carotid sinus. PMID- 3344953 TI - Consultants and pre-operative visits. PMID- 3344954 TI - Premedication and postoperative vomiting. PMID- 3344955 TI - Unstable cervical fracture. PMID- 3344957 TI - Spinal anaesthesia after facet joint injection. PMID- 3344956 TI - Pain-free intravenous injections. PMID- 3344958 TI - Arterial oxygen saturation during general anaesthesia for dental extraction in children. PMID- 3344959 TI - A paediatric scavenging valve. PMID- 3344960 TI - A cause of apparent resistance to thiopentone. PMID- 3344961 TI - Distress caused by urethral catheters. PMID- 3344962 TI - Epidural catheter migration during labour. PMID- 3344963 TI - Risks of infection from water bath blood warmers. PMID- 3344965 TI - Confirmation of tracheal tube placement. PMID- 3344966 TI - 'Right at your fingertips'--is the oximeter only half the story? PMID- 3344964 TI - Failure of external cardiac compression. PMID- 3344967 TI - Low volume, high concentration block of the sciatic nerve. AB - Sciatic nerve block was performed in two groups of patients using a low power peripheral nerve stimulator to aid nerve location. In group A 1% prilocaine with felypressin was used as the local anaesthetic agent in a volume of 0.25 ml/kg body weight. In group B 3% prilocaine with felypressin was used in a volume of 0.08 ml/kg body weight (i.e. equal total drug dosages). Use of the 3% solution resulted in highly significant reductions in the mean latency for analgesia of the nerve block and in the latency and degree of motor block achieved (p less than 0.005 in each case). The clinical value of high concentration, low volume nerve block is discussed. PMID- 3344968 TI - Determination of chromium(III) and chromium(IV) by ammonium pyrrolidinecarbodithioate-methyl isobutyl ketone furnace atomic absorption spectrometry. PMID- 3344969 TI - Use of 1H nuclear magnetic resonance longitudinal relaxation times in structure elucidation of chlorinated polyaromatic compounds. PMID- 3344970 TI - Bioaccumulation and measurement of copper at an alga-modified carbon paste electrode. PMID- 3344971 TI - Simplex optimization of a fiber-optic ammonia sensor based on multiple indicators. PMID- 3344972 TI - Highly selective protein separations with reversed micellar liquid membranes. PMID- 3344974 TI - Regional hemodynamics and oxygen supply during isovolemic hemodilution alone and in combination with adenosine-induced controlled hypotension. AB - Studies were performed in ten pentobarbital-anesthetized, open chest dogs to evaluate regional circulatory effects of isovolemic hemodilution alone, and in combination with adenosine-induced controlled hypotension. Regional blood flow measured with 15-microns radioactive microspheres was used to calculate regional oxygen supply. Hemodilution with 5% dextran (40,000 molecular weight) reduced arterial hematocrit and oxygen content by approximately one-half and caused heterogeneous changes in regional blood flows; flow decreased in the spleen, was unchanged in the renal cortex, liver, skeletal muscle and skin, and increased in the duodenum, pancreas, brain and myocardium; however, only in the brain and myocardium were increases in flow sufficient to preserve oxygen supply. Intravenous infusion of adenosine reduced aortic pressure by 50% and reduced flow in most tissues (renal cortex, pancreas, liver, spleen, skin, and brain), with the result that oxygen deficits were produced or accentuated in these organs. The magnitude of flow reductions in the renal cortex (-73%) and cerebral cortex ( 37%) were noteworthy. In the myocardium, direct coronary vasodilation by adenosine caused parallel increases in blood flow and oxygen supply to levels exceeding prevailing metabolic requirements. It is concluded that 1) during isovolemic hemodilution alone, oxygen supply to the brain and myocardium is maintained at the expense of oxygen supply to less critical organs and, 2) during combined isovolemic hemodilution and adenosine-induced hypotension, oxygen is oversupplied to the myocardium but undersupplied to the brain and kidney. These latter effects suggest the need for extensive clinical monitoring of patients in whom combined isovolemic hemodilution and adenosine-induced hypotension is utilized. PMID- 3344973 TI - Intravenous diltiazem worsens regional function in compromised myocardium. AB - The effect of intravenous diltiazem on regional myocardial function was assessed in a canine model of critical constriction of the left anterior descending coronary artery (LAD). Maintenance anesthesia with fentanyl (1.5 micrograms.kg 1.min-1), 60% inspired nitrous oxide, and 0.7% inspired halothane resulted in regional dysfunction, measured as postsystolic shortening (20.6 +/- 10.7%), which was significantly worsened after 0.1 mg/kg (48.7 +/- 12.5%, P less than 0.05) and after 0.2 mg/kg (68.8 +/- 11.7%, P less than 0.05) intravenous diltiazem. Systolic shortening in the compromised LAD territory was substantially depressed after 0.1 mg/kg diltiazem (8.2 +/- 0.6% to 5.3 +/- 1.3%, P less than 0.05) and was essentially abolished after 0.2 mg/kg diltiazem (8.2 +/- 0.6% to 0.7 +/- 2.3%, P less than 0.05). At the higher dose of diltiazem, cardiac output was substantially decreased (1.37 +/- 0.23 L/min to 0.88 +/- 0.30 L/min, P less than 0.05) and LV dP/dtmax significantly depressed (1090 +/- 90 mm Hg/sec to 744 +/- 80 mm Hg/sec, P less than 0.05). These results demonstrate significant depression of regional systolic shortening and substantial worsening of regional dysfunction in myocardium with a compromised blood supply, in association with significant depression of left ventricular performance, with intravenous diltiazem administration during anesthesia. PMID- 3344975 TI - Effects of tracheal intubation on laryngeal acoustic waveforms. AB - To assess the feasibility of noninvasive detection of laryngeal injury after tracheal intubation through acoustic waveform measurements, we studied the effects of intubation on "time-expanded" acoustic waveforms of the larynx in 16 patients given general anesthesia, 9 with and 7 without tracheal intubation. Recordings of several utterances were obtained by means of a microphone and an accelerometer attached to the skin at the midpoint of the suprasternal notch. Recordings were taken the day before induction of general anesthesia, 20 minutes after extubation, and 2 and 4 days after extubation. Waveforms of the recordings were subsequently assessed visually for features different from those of normal phonation as determined in preliminary studies. Waveforms in several of the recordings taken soon after extubation showed marked intraperiod and interperiod irregularities. These abnormalities improved and disappeared over the following 4 days. No changes were observed in the acoustic waveforms of seven patients given general anesthesia without tracheal intubation. The analysis of time-expanded acoustic waveforms of the larynx indicates that this technique has considerable potential as a sensitive, noninvasive technique that helps to evaluate the effects of tracheal intubation on laryngeal function, a technique that warrants further study and evaluation. PMID- 3344976 TI - Comparison of buprenorphine with morphine in the treatment of postoperative pain in children. AB - The safety and efficacy of buprenorphine and morphine as postoperative analgesics for children were compared in 60 boys and girls 4 to 14 years old having elective orthopedic operations on upper or lower extremities. The drugs were given in a double-blind manner initially intravenously and thereafter by sublingual buprenorphine or intramuscular morphine administered as required to relieve pain until the third postoperative morning. The IV dose needed to achieve complete initial analgesia was 5.2 +/- 2.8 micrograms/kg buprenorphine and 166 +/- 100 micrograms/kg morphine. The duration of effect was significantly longer with buprenorphine than with morphine, 248 +/- 314 and 114 +/- 109 minutes, respectively (P = 0.03). The most common side effects were nausea and vomiting (28 and 16%) and urinary retention (21 and 19%) in the buprenorphine and morphine groups, respectively. Analgesia with sublingual buprenorphine was as effective and reliable as with intramuscular morphine but a longer duration of action could not be demonstrated. PMID- 3344977 TI - The temperature of bupivacaine 0.5% affects the sensory level of spinal anesthesia. AB - Three milliliters of plain bupivacaine 0.5% was injected intrathecally in two groups of 20 patients. Group 1 received a solution that had been equilibrated to 37 degrees C, group 2 received a solution that had been equilibrated to 4 degrees C. Patients were kept sitting for 3 minutes after injection. All observations were observer-blind. The differences between segmental levels of sensory loss between groups 1 and 2 (T4 and T9, respectively) and of temperature loss (T3 and T8, respectively) 10 and 20 minutes after injection of bupivacaine were statistically significant. It is concluded that the time needed for thermal equilibration in the cerebrospinal fluid and hence temperature of the injected solution plays an important role in the sensory spread of plain bupivacaine 0.5%. PMID- 3344978 TI - Nerve injury and musculoskeletal complaints after cardiac surgery: influence of internal mammary artery dissection and left arm position. PMID- 3344979 TI - Postoperative arterial oxygen saturation in the pediatric population during transportation. PMID- 3344980 TI - Continuous intravenous midazolam infusion for sedation in the pediatric intensive care unit. PMID- 3344981 TI - Acute postoperative delirium and extrapyramidal signs in a previously healthy parturient. PMID- 3344982 TI - Modular intravenous transport system. PMID- 3344983 TI - Preventing kinking of small endotracheal tubes. PMID- 3344984 TI - Epidermolysis bullosa and porphyria. PMID- 3344985 TI - Demonstrating safety of subarachnoid calcitonin: patients or animals? PMID- 3344986 TI - Subarachnoid lidocaine and calcitonin for postoperative analgesia. PMID- 3344987 TI - The effect of age on plasma clearance of epidural lidocaine and bupivacaine. PMID- 3344988 TI - Drug effects on urinary bladder tone during spinal morphine-induced inhibition of the micturition reflex in unanesthetized rats. AB - In an unanesthetized chronic rat model involving the placement of one catheter in the bladder for cystometrography and one catheter in the intrathecal (IT) space for drug injections, 10 micrograms morphine sulfate injected intrathecally (it) produced long-lasting inhibition of the volume-evoked micturition reflex. During inhibition of the micturition reflex, intravesical pressure rose with infusion until a continuous emission of urine (dribbling) was observed. Such a level of intravesical pressure (overflow pressure) was significantly greater than the premorphine bladder opening pressure (+56%). During dribbling, no periodic vesical contractions were observed, and the effects of a variety of agents on bladder tone were assessed. Significant (P less than 0.05) increases in vesical pressure over that produced by morphine were observed after intraperitoneal (ip) injection of carbachol (+86%), bethanechol (+55%), norepinephrine (+53%), methoxamine (+88%), and ST-91, an alpha 2-adrenergic agonist (+70%). The increased vesical pressure was not accompanied by an increase in the rate of urine expression. Intraperitoneal injection of serotonin produced no effects on intravesical pressure or urine expression. Significant decreases in the otherwise elevated intravesical pressure were observed after ip injection of isoproterenol (-30%) and phentolamine (-21%), with no change in the rate of urine expression. In contrast, ip injection of apomorphine (dopamine agonist) resulted in significant decreases in vesical pressure (-49%) and near maximal emptying of the bladder. Apomorphine produced no effects on it morphine-induced antinociception as assessed by the tail flick response. Regarding potential treatments of spinal morphine-induced urinary retention, the present study suggests that: 1) cholinomimetic and alpha-adrenergic agonist agents might be harmful; 2) beta adrenergic agonist and alpha-adrenergic blocking agents might be useful; and 3) dopaminergic agonist agents might be the drugs of choice. PMID- 3344989 TI - Epidural clonidine does not decrease blood pressure or spinal cord blood flow in awake sheep. AB - Preliminary data in animals and humans suggest that epidurally administered clonidine produces antinociception and is not neurotoxic. However, clonidine can produce vasoconstriction, and epidurally administered clonidine decreases spinal cord blood flow in anesthetized pigs. To examine the effect of epidurally administered clonidine on spinal cord blood flow in awake animals, the authors inserted lumbar epidural, femoral arterial and venous, pulmonary arterial, and left ventricular catheters in 13 adult sheep. Following a 24-h recovery, the authors injected saline (N = 6) or clonidine, 750 micrograms (17-25 micrograms/kg; N = 7) epidurally, and measured arterial blood gas tensions; temperature; heart rate; systemic and pulmonary arterial, right atrial, and pulmonary capillary wedge pressures; and spinal cord and renal blood flows (by radioactive microsphere injection) before and at 45 min and 4 h following injection. Epidural saline injection did not affect measured variables. Heart rate decreased from 112 +/- 9 to 86 +/- 4 beats/min (mean +/- SE; P = .003) and arterial PO2 decreased from 99 +/- 3 to 78 +/- 6 mmHg (P = .04) 45 min following clonidine injection. Temperature increased from 39.1 +/- .2 to 40.6 +/- 1 degree C (P = .0001) 4 h following clonidine injection. Epidural clonidine administration did not affect cardiac output, pulmonary and systemic pressures, or renal or spinal cord blood flows, except for an increase in mid-thoracic spinal cord blood flow 45 min following injection. The authors conclude that, in sheep, epidural clonidine does not produce dangerous cardiovascular depression or global spinal cord ischemia. PMID- 3344990 TI - Capsaicin sensitive afferents contribute to acute airway edema following tracheal instillation of hydrochloric acid or gastric juice in the rat. AB - The formation of acute edema in the tracheobronchial mucosa following local instillation of hydrochloric acid or gastric juice was studied in rats. Protein extravasation using the Evans blue technique was measured and used to indicate edema formation. A pH dependent Evans blue extravasation was observed whereby pH 2 produced a small, pH 1.5 an intermediate, and pH 1 a pronounced effect. Also, gastric juice (pH 1.3 +/- 0.1) induced a marked Evans blue extravasation in the tracheobronchial mucosa. Rats which had been pretreated with capsaicin (100 mg/kg s.c.) had a much lower Evans blue extravasation following local instillation of both hydrochloric acid and gastric juice. Thus, the increase in Evans blue content induced by acid at pH 1.5 was abolished while about 50% of the response remained at pH 1. The protein extravasation caused by gastric juice was reduced by about 70% after capsaicin treatment. Terbutaline (73 nmol/kg, iv) or enprophylline (25 mumol/kg, iv) injected intravenously 10 min before, as well as hydrocortisone injected immediately after the intratracheal instillation of gastric juice, did not influence the magnitude of edema formation. Beta-methasone (0.25 mg/kg ip) pretreatment 24 h prior to the gastric juice exposure enhanced tracheal extravasation. In conclusion, acute protein extravasation in the lower airway mucosa induced by hydrochloric acid or gastric juice is mainly dependent on capsaicin sensitive sensory nerves, suggesting that local release of mediators, such as tachykinins, play a key role in this reaction. PMID- 3344991 TI - The effect of vasopressor agents upon uterine artery blood flow velocity in the gravid guinea pig subjected to ritodrine infusion. AB - The purpose of the present study was to assess the effects of intravenously administered vasopressors upon uterine artery blood flow velocity (UBFV) in the gravid guinea pig subjected to ritodrine infusion. Fourteen experiments were performed in 14 chronically instrumented pregnant guinea pigs near term. Immediately following a 1-h intravenous infusion of ritodrine (0.05-0.20 mg.kg.min-1), each animal received an intravenous bolus of vasopressor solution: 1) epinephrine, 0.001 mg/kg; 2) phenylephrine, 0.01 mg/kg; 3) mephentermine, 1.0 mg/kg; 4) ephedrine, 1.0 mg/kg; or 5) placebo. The experimental sequence was performed five times, so that each animal received all five solutions. The vasopressor sequence was randomly altered between animals. Infusion of ritodrine increased maternal heart rate 18 +/- 1% (P less than .0001), decreased maternal mean arterial pressure (MMAP) 4 +/- 1% (P less than .01), and decreased UBFV 5 +/ 1% (P less than .001). The four active vasopressor solutions resulted in similar, though not equivalent, increases in MMAP. Further, the MMAP response to each active vasopressor differed from the response to placebo (P less than .0001). Epinephrine and phenylephrine each significantly decreased UBFV (P less than .002). Ephedrine clearly preserved UBFV, whereas mephentermine appeared to result in an intermediate response. PMID- 3344992 TI - Improvement of diaphragmatic function by a thoracic extradural block after upper abdominal surgery. AB - The effects on diaphragmatic function of a thoracic epidural block were assessed in 13 patients after upper abdominal surgery (UAS). Lung volumes and tidal changes in chest wall circumferences and gastric (delta Pgas) and esophageal (delta Pes) pressures were measured pre- and postoperatively. Volume displacement of the abdomen divided by tidal volume (delta VAB/VT) and delta Pgas/delta Pes were taken as indices of the diaphragmatic contribution to tidal breathing. These respiratory variables were obtained in the postoperative period, before and after epidural injection of 0.5% plain bupivacaine to achieve a block up to the T4 segment. UAS was constantly associated with a decrease in VT, delta VAB/VT, delta Pgas/delta Pes, and forced vital capacity (FVC). Epidural block was associated with an increase in VT, delta VAB/VT, and FVC. delta Pgas and delta Pgas/delta Pes returned to their preoperative values. It is concluded that: 1) diaphragmatic dysfunction observed after UAS is partially reversed by thoracic epidural block; and 2) that inhibitory reflexes of phrenic activity arising from the abdominal compartment (abdominal wall and/or viscera) could be involved in this diaphragmatic dysfunction. PMID- 3344993 TI - Pharmacokinetics of bupivacaine following caudal anesthesia in infants. AB - Pharmacokinetics and protein binding of bupivacaine were studied after caudal injection of 2.5 mg/kg in 13 ASA PS 1 infants (1-6 months of age) scheduled for elective hernia repair. Blood was sampled at frequent intervals from 5 min to 600 min in all but one patients. Additional samples were taken at 720 and 840 min in five patients. Bupivacaine concentration was measured using gas chromatography. Protein binding was measured using ultrafiltration. Peak serum concentrations ranged between 0.55 and 1.93 micrograms/ml. The time to reach the peak ranged from 10 to 60 min. Terminal half-life (T1/2 beta) was 7.7 +/- 2.4h (mean +/- SD), the volume of distribution (Vss) was 3.9 +/- 2.01.kg, and the total body clearance (CL) was 7.1 +/- 3.2 ml.min.kg-1. The free fraction was markedly increased (0.16 +/- 0.07) when compared with published adult values, and showed a highly significant negative correlation with age. Alpha 1 acid glycoprotein measured in the same infants correlated significantly with age. In conclusion, pharmacokinetics of caudal bupivacaine in infants are characterized by Cmax of total drug similar to those observed in adults after epidural injection. The free fraction is increased at least until 6 months of life. This suggests caution in the use of bupivacaine in infants until we understand the clinical significance of this increased free fraction. PMID- 3344994 TI - Morphine tolerance decreases the analgesic effects of ketamine in mice. AB - Previous studies have shown that ketamine interacts with opiate receptors, and it has been suggested that ketamine-induced analgesia is mediated through opiate receptors. If so, ketamine should produce less analgesia in morphine tolerant animals, just as morphine does. To test this hypothesis, the analgesic effects of ketamine were tested in mice implanted with placebo pellets and in mice made tolerant to morphine through implantation of morphine pellets, using the abdominal constriction test. The test consisted of ip injection of 1% acetic acid, which caused stretching of hind limbs and constriction of abdominal muscles, also called writing. The number of writhes was counted for each mouse 10 15 min following acetic acid injection. Morphine pellet implanted mice treated with saline writhed 12.2 +/- 0.8 times (mean +/- SEM), not significantly different from 9.8 +/- 0.9 times seen in placebo pellet implanted mice. Treatment of the animals with ketamine at three doses of 20, 25, and 30 mg/kg, subcutaneously (sc), reduced the number of writhes in the placebo pellet implanted group to 5.8 +/- 0.8, 4.2 +/- 0.7, and 1.3 +/- 0.3, respectively. In the morphine pellet-implanted group, with the same doses of ketamine, the numbers of writhes were 10 +/- 0.9, 9.3 +/- 1.1, and 5.2 +/- 0.9, respectively. Morphine tolerant animals writhed significantly more at each dose of ketamine, indicating that they were cross tolerant to the analgesic effects of ketamine. PMID- 3344995 TI - Burn injury to rat increases nicotinic acetylcholine receptors in the diaphragm. AB - Thermal injury induces aberrant responses to neuromuscular (NM) blocking drugs, and it has been speculated that an increase in nicotinic acetylcholine receptors (AchR) may contribute to the altered response. Using the diaphragmatic muscle as a representative of skeletal muscle, the changes in AchR were examined. The diaphragm, rather than limb muscles, was chosen to avoid the effects of wound contracture-induced immobilization and denervation of limb, which can also increase AchR in skeletal muscle. Study of changes in diaphragm also tested the hypothesis that increase in AchR are the result of a generalized systemic effect, and not limited to area of burn. Following a 45-55% body surface area thermal injury to the trunk (not limbs) of rats, AchR changes in the diaphragm were studied at 10, 14, 21, and 28 days after injury and compared to uninjured (control) rats. The AchR changes in the diaphragmatic muscle was assayed using 125I-alpha-bungarotoxin as the specific ligand. At 10, 14, and 21 days after thermal injury, the animals had an arrest in weight growth and the AchR concentration was increased to (mean +/- SE) 155 +/- 15% (P less than 0.02), 160 +/- 16% (P less than 0.003), and 141 +/- 16% (0.05 less than P less than 0.1), respectively, compared to control. At 28 days, probably because of wound healing and burn wound contracture, the size of thermally injured area was significantly (P less than 0.001) reduced to 19 +/- 4% of body surface area, and weight increased (P less than 0.001) compared to preburn weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344996 TI - Nitrous oxide worsens myocardial ischemia in isoflurane-anesthetized dogs. AB - Two equipotent anesthetic regimens, isoflurane 1.8% in 50% nitrogen/oxygen and isoflurane 1.4% in 50% nitrous oxide/oxygen, were compared to test if nitrous oxide, without changing the depth of anesthesia, can affect myocardial function, blood flow, and metabolism in an ischemic region of the heart. In 14 dogs, anesthesia was induced with sodium thiopental. Following tracheal intubation, they were ventilated with isoflurane in oxygen. The chest was opened, the LAD coronary artery cannulated, and flow to it controlled with an autoperfusion circuit. Systolic shortening in the LAD and circumflex regions was measured with a sonomicrometer via pairs of piezo-electric crystals placed in the subendocardium. Regional myocardial blood flow was measured with radioactive microspheres injected into the left atrium. Regional myocardial lactate metabolism was assessed by withdrawing blood from a catheter placed in the anterior cardiac vein. Measurements were made during the imposition of a stenosis on the perfusion circuit sufficient to decrease systolic shortening by 10-20%. The same stenosis was imposed three times in a randomized and balanced crossover design. Treatment with nitrous oxide was associated with small increases in heart rate and systolic blood pressure (5 and 8%, respectively), as well as a 19% reduction in systolic shortening and a 30% fall in endo/epi blood flow ratio in the hypoperfused LAD region distal to the stenosis. Lactate extraction was low or negative during both anesthetics, but differences were not statistically significant. The data indicate that the substitution of 50% nitrous oxide for 0.4% isoflurane caused a reduction in mechanical function and a further maldistribution of blood flow in ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3344997 TI - Effects of adenosine-induced hypotension on myocardial hemodynamics and metabolism in fentanyl anesthetized patients with peripheral vascular disease. AB - The effects of adenosine on central and myocardial hemodynamics and metabolism were evaluated during fentanyl anesthesia (100 micrograms.kg-1) in six patients with peripheral vascular disease. Adenosine was intravenously infused, at a rate of 90 +/- 20 (SEM) micrograms.kg-1.min-1, to reduce mean arterial blood pressure by approximately 20% (23 +/- 2% SEM, from 82 +/- 3 to 63 +/- 3 SEM mmHg) during a 20-min period. Systemic and pulmonary vascular resistance indices decreased by 36 +/- 3 and 32 +/- 6% (SEM), and cardiac index increased by 18 +/- 5%. Heart rate, ventricular filling pressures, and whole body oxygen consumption were not affected by adenosine. Despite the reduced mean arterial blood pressure, coronary sinus flow increased by 128 +/- 26% (SEM) in parallel with a 96 +/- 11% (SEM) increase in coronary sinus oxygen content. Left and right ventricular stroke work indices, as well as myocardial oxygen consumption, were maintained. ECG (12-lead) demonstrated signs of ischemia in one subject, while myocardial lactate uptake was unchanged in all subjects. In conclusion, adenosine-induced hypotension in patients with peripheral vascular disease increased cardiac index without affecting myocardial work, whole body, and myocardial oxygen consumptions. The marked increase in coronary sinus blood flow, indicating coronary vasodilation, was not related to increased myocardial work. Further information regarding myocardial effect of adenosine in patients with ischemic heart disease is warranted. PMID- 3344998 TI - Effects of halothane and isoflurane on isolated human ventricular myocardium. AB - Segments of viable human left ventricular trabeculae were obtained at the time of endocardial resection for intractable ventricular ectopy. Muscle segments which showed suitable and reproducible contractions in 26 mM K Tyrode solution with 1 microM isoproterenol were electrically stimulated after rest, and at frequencies of 0.1, 0.25, 0.5, and 1 Hz. Effects of 0.75% halothane and 1.3% isoflurane on peak tension, maximum rate of tension development (dT/dt-max), and on slow (calcium dependent) action potential (AP) characteristics were studied. Halothane depressed peak tension, dT/dt-max, and slow AP maximum rate of depolarization (Vmax) at all frequencies, and caused a significantly greater depression of peak tension and dT/dt-max at 0.5-1 Hz than after rest and at 0.1-0.25 Hz. Isoflurane did not significantly depress slow AP Vmax, showed no frequency dependent contractile depression, and depressed dT/dt-max less than halothane at 0.5 and 1 Hz. Halothane and isoflurane caused differing depression in the pattern of developed tension. The differential depression by halothane and isoflurane of human ventricular myocardium was similar to that previously observed in isolated animal ventricular tissue. PMID- 3344999 TI - Effect of preeclampsia on carboxyhemoglobin levels: a mechanism for a decrease in P50. AB - COHb levels were measured in 15 preeclamptic pregnant women and 15 normal pregnant women to investigate the cause for the decrease in P50 associated with preeclampsia. The authors also included six normal and six preeclamptic pregnant patients from the above groups in the determination of P50. Measurements of COHb levels were performed in a Radiometer OSM2 Hemoximeter. Determination of P50 was done using an IL 237 Tonometer, a Radiometer, OSM2 Hemoximeter, and a Corning 168 pH/Blood Gas Analyzer. Preeclamptic pregnant patients had a mean COHb level of 2.8%, whereas normal pregnant women had a mean COHb level of 0.7% (P less than 0.001). Preeclamptic patients also had a significantly lower (24.4 mmHg) P50 than normal pregnant women (P50 = 30.1 mmHg) (P less than 0.001). The authors conclude that a significant elevation of COHb in preeclamptic pregnant women is partly responsible for a significant decrease in P50 seen in preeclampsia. PMID- 3345000 TI - Comparison of MAC and the rate of rise of alveolar concentration of sevoflurane with halothane and isoflurane in the dog. AB - The anesthetic requirements for sevoflurane, isoflurane, and halothane were determined in mongrel dogs. The MACs (minimum alveolar concentration) of sevoflurane, isoflurane, and halothane were 2.36 +/- 0.46% (n = 18), 1.39 +/- 0.25% (n = 10), and 0.89 +/- 0.20% (n = 12), respectively (mean +/- SD). In agreement with sevoflurane's low blood/gas partition coefficient (0.6), the rate of rise of alveolar concentration toward that inspired (FA/FI) for sevoflurane was significantly faster than that for either halothane or isoflurane. Thirty seconds after breathing a constant inspired concentration FA/FI was 0.75 for sevoflurane, which was 2.96 times higher than that with halothane (0.25 +/- 0.02) and 1.29 times higher than that with isoflurane (0.6 +/- 0.05). Induction with sevoflurane was smooth, with no struggling nor excessive salivation. PMID- 3345001 TI - Reconstruction of the trachea in children with tracheal stenosis by using jet ventilation. PMID- 3345002 TI - Patient-controlled analgesia following cesarean section: a comparison with epidural and intramuscular narcotics. PMID- 3345003 TI - Venous air embolism during removal of tissue expander in a supine child. PMID- 3345004 TI - Effect and interaction of pH and lidocaine on epinephrine absorption. PMID- 3345005 TI - Anesthesia-related complications in children with Duchenne muscular dystrophy. PMID- 3345006 TI - Regional anesthesia in children with epidermolysis bullosa dystrophica. PMID- 3345007 TI - Lidocaine and cerebral metabolism. PMID- 3345008 TI - Differences in the response of humans and dogs to succinyldicholine. PMID- 3345009 TI - Tracheal pH during endotracheal anesthesia. PMID- 3345011 TI - Unintentional lethal/toxic injections: elimination of drugs versus vigilance. PMID- 3345010 TI - Minimum drug dose to obtain adequate amnesia for cardioversion. PMID- 3345012 TI - Life-threatening ECG artifact during extracorporeal shock wave lithotripsy. PMID- 3345014 TI - The emergency department ECG and immediately life-threatening complications in initially uncomplicated suspected myocardial ischemia. AB - The emergency physician's disposition of patients with suspected myocardial ischemia is currently debated; some physicians believe that a subgroup of patients can be managed safely outside the coronary care unit. Clinical predictors are needed in assessing the patient with suspected myocardial ischemia to help identify this subgroup. Through a retrospective cohort study, we investigated the value of the initial emergency department ECG in discriminating between chest pain patients with low and high risk for immediately life threatening complications. Two hundred eleven initially uncomplicated consecutive coronary care unit admissions with suspected unstable angina or myocardial infarction were studied. Patient outcome, including the incidence of myocardial infarction, complications, and mechanical and pharmacologic interventions, was reviewed. Immediately life-threatening complications included ventricular fibrillation, ventricular tachycardia, shock, 2 degrees and 3 degrees block, and death. Mechanical interventions included electrocardioversion or defibrillation, endotracheal intubation, intra-aortic balloon pump, Swan-Ganz catheter, or pacemaker insertion. Pressors, antiarrhythmics, and vasodilators were the reviewed pharmacologic interventions. A positive ECG was defined by the presence of ST elevation or depression, T wave inversion, left ventricular hypertrophy, left bundle branch block, paced rhythm, or new Q waves. All other ECG interpretations were considered negative. Patients were divided into two groups based on this initial emergency physician ECG interpretation and their complication incidences compared. Of the 211 patients, 96 had a positive ECG; 115 had negative ECGs. Patients with positive ECGs were older, had a greater history and concurrent incidence of myocardial infarction, and more complications and intensive interventions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345013 TI - An emergency physician's guide to prosthetic heart valves: identification and hemodynamic function. AB - We describe methods for identifying the type and size of seven commonly used prosthetic heart valves and how these features influence the hemodynamics of flow through the valve. The four mechanical heart valves reviewed are Starr-Edwards silicone rubber ball valves (Models 1200/1260 aortic and 6120 mitral valves), Bjork-Shiley tilting disc valves (60 degrees standard spherical model and the 60 degrees convexo-concave model), Medtronic-Hall (Hall-Kaster) tilting disc valve, and St Jude Medical bileaflet valve. The three bioprostheses reviewed are Hancock porcine valve, Carpentier-Edwards porcine valve, and Ionescu-Shiley bovine pericardial valve. These valves were chosen because of their past or present popularity and therefore are the ones most apt to be implanted in patients seen in the emergency department. PMID- 3345015 TI - Absence of a tachycardic response to shock in penetrating intraperitoneal injury. AB - The belief that tachycardia is an early and reliable indicator of shock has recently been challenged. We examined 144 battlefield casualties with penetrating intraperitoneal injury to determine whether patients in shock presented with pulse rates that were significantly more rapid than those in patients not in shock. No differences in mean pulse rates were found when using objective operational definitions of shock. In contrast, the only pulse rate difference was noted when shock was defined on the basis of the surgeon's subjective clinical impression and this was attributed to selection bias. The absence of a tachycardic response in battlefield casualties with penetrating abdominal wounds cannot be taken as an indication that serious injury and significant intraperitoneal bleeding have not occurred. Caution should be exercised when using this parameter as a guide for therapeutic interventions, and further study is indicated to determine whether a similar pattern is seen in civilian practice. PMID- 3345016 TI - Prehospital use of neuromuscular blocking agents in a helicopter ambulance program. AB - We prospectively studied the use of succinylcholine chloride and pancuronium bromide by the physician/nurse flight team of our hospital-based helicopter ambulance service. Patients who received these agents at the scene of an accident (prehospital group, n = 39) were compared with patients who were paralyzed by the flight team in the emergency department of transferring hospitals (control group, n = 35). By protocol, succinylcholine was used primarily for endotracheal intubation and pancuronium for prolonged paralysis after endotracheal intubation. Seventy-four patients received one or both agents. Overall, 61 of 74 patients had intracranial pathology as their primary diagnosis (82%). Endotracheal intubation was the primary indication for paralysis in the majority of patients (67 of 74), although intracranial pressure control, ventilation, agitation control, and seizure control were frequent secondary indications. Prior intubation attempts had failed in 40 of 74 patients (54%). After paralysis, intubation was successful in 68 of 71 patients (96%). Serious complications (ie, dysrhythmia requiring drug therapy) occurred in three patients but resolved with appropriate therapy in each case. Minor complications (ie, dysrhythmia not requiring drug therapy, histamine flush, infiltrated IV line) occurred in 18 patients. There was no significant difference in successful intubation or complication rate between the prehospital and control group. Paralysis allowed airway stabilization in a significant number of critically ill patients who could not otherwise be endotracheally intubated, with a lower incidence of complications than has been previously reported for ED patients. These results suggest that neuromuscular blocking agents can be used safely and effectively at accident scenes by a physician/nurse team. PMID- 3345017 TI - Sorbitol catharsis does not enhance efficacy of charcoal in a simulated acetaminophen overdose. AB - The use of a 70% sorbitol solution has recently been advocated as an adjunct to activated charcoal. This results in rapid and profuse catharsis that could possibly cause fluid and electrolyte imbalance. An investigation was undertaken to determine if sorbitol catharsis enhanced the antidotal efficacy of activated charcoal. Eight healthy volunteers participated in a randomized, crossover trial. Subjects ingested 3 g of acetaminophen followed by either no intervention, 50 g of plain activated charcoal at one hour, or 50 g activated charcoal-sorbitol solution at one hour. Serial acetaminophen levels were determined at intervals over eight hours and side effects noted. Both interventions significantly reduced the area under the curve versus control (P less than .05). The addition of sorbitol did not enhance the efficacy of activated charcoal but did increase the side effects noted. Sorbitol has not been proven effective in enhancing drug removal and has side effects that can be significant in a poisoned patient. Current data do not warrant its use, and further investigations should be carried out with other ingested drugs. PMID- 3345019 TI - Do urine dipsticks reliably predict microhematuria? The bloody truth! AB - Some literature has cast doubt on the reliability of urine dipsticks in the search for microhematuria. In our study, 2,000 urine dipsticks (two brands) were tested on urine samples containing 0, 0 to 5, 5 to 10, 10 to 20, and 20 to 50 red blood cells per high-power field. The same samples were retested four hours later and the same sticks were tested after four months of aging. Variables controlled for included observer, lighting, performance according to package insert, pH, specific gravity, white blood cells, ascorbic acid, protein, age of dipstick, and exposure of urine to povidine or cleaning solutions. Results obtained using both N-Multistix and Chemstrip 9 urine dipsticks correlated closely with the degree of hematuria. Overall sensitivity was 100%, and specificity was 99.3%. We conclude that these urine dipsticks are reliable and are not affected when tested on urine four hours after void, and that Chemstrips 9 are much more reliable than are N Multistix if aged in air for four months. PMID- 3345018 TI - Outcome of self-inflicted gunshot wounds of the brain. AB - A consecutive series of 67 patients who had sustained self-inflicted gunshot wounds of the brain was reviewed retrospectively to evaluate factors determining outcome. Weapon caliber, site of bullet entry, degree of brain wounding on computerized tomographic scan, and presenting Glasgow Coma Scale (GCS) score were examined. Overall mortality, degree of disability in survivors, and survival time after injury in fatally wounded patients were assessed. Ninety-eight percent of all patients with an initial GCS score of 8 or less died. When the GCS score was more than 8, 91% of patients survived (P less than .0001). Survival rate was significantly increased in patients with injury limited to one lobe of the brain, compared with patients with brain wounds of greater severity demonstrated on computerized tomographic scan (P less than .05), while a missile crossing both vertical anatomic planes of the brain or coming to rest in the posterior fossa was lethal in 100% of cases. Survivors scored relatively well on the Glasgow Outcome Scale. Almost all (98%) fatally injured patients maintained vital functions for a time ample for transportation and evaluation at a major referral center. These findings hold important implications for trauma center and critical care resource allocation as well as organ transplantation programs. PMID- 3345020 TI - Nausea, dyspnea, and heart block in an 86-year-old patient with congestive heart failure. PMID- 3345021 TI - Amoxapine cardiotoxicity. AB - Prolongation of the QRS interval, cardiopulmonary arrest, and death in a 31-year old woman following an overdose of 2 g amoxapine, a tricyclic antidepressant, is reported. The patient's QRS interval prolonged to beyond 100 ms throughout hospitalization. Thirty-three hours after admission she suffered a bradycardiac hypotensive event, followed by electromechanical dissociation and subsequent death. Cardiotoxicity has not been directly related to amoxapine; a 2-g acute ingestion is the lowest reported lethal dose. PMID- 3345022 TI - Ventricular tachycardia related to transcutaneous pacing. AB - A 3-year-old child with Haemophilus influenzae endocarditis and aortic route abscesses presented with sudden cardiovascular collapse. During resuscitation, the child was noted to be in complete heart block. Transcutaneous pacing was instituted three times, and ventricular dysrhythmias were associated with each pacing attempt. When pacing was discontinued, the patient spontaneously reverted to complete heart block without ventricular ectopy. An emergency thoracotomy revealed rupture of the aortic route, and the patient died during surgery. Transcutaneous pacing may precipitate serious dysrhythmias; appropriate precautions are recommended. PMID- 3345023 TI - The use of labetalol in the management of cocaine crisis. AB - We report a case of successful resuscitation and clinical management in a 31-year old man who allegedly ingested 20 g of cocaine hydrochloride. The physiologic and pharmacologic mechanisms of cocaine toxicity are reviewed. The use of labetalol in resolving the cardiovascular crisis is specifically detailed. PMID- 3345024 TI - Chronic contained rupture of an abdominal aortic aneurysm presenting as a lower extremity neuropathy. AB - Rupture of an abdominal aortic aneurysm often presents with a pulsatile abdominal mass, abdominal pain, and hypotension. Recent clinical reports describe patients with less apparent clinical signs and symptoms who were found later in their evaluation to have a contained rupture of an abdominal aortic aneurysm. Even more unusual is a chronic contained rupture of an abdominal aortic aneurysm. Our patient had a chronic contained rupture of an abdominal aortic aneurysm that presented with erosion into the lumbar vertebral bodies and subsequent lumbar neuropathy. CT scan confirmed the contained rupture of the aortic aneurysm and the patient underwent successful repair of his aortic aneurysm. Our report discusses the significance of atypical presentations of abdominal aortic aneurysm rupture and the importance of prompt diagnosis and definitive repair. PMID- 3345025 TI - Acute respiratory arrest due to hypokalemia. AB - An uncommon but treatable etiology of acute respiratory failure is hypokalemia. A 36-year-old woman with previously undiagnosed distal renal tubular acidosis presented with foot and ankle swelling that was being treated with furosemide. She had been seen by three physicians within 24 hours and was diagnosed as having depression or hysterical conversion reaction. Her symptoms progressed to respiratory arrest. Initial treatment consisted of administering 40 mEq of KCl over one hour through a central venous line. The patient recovered rapidly and was weaned off a respirator within 24 hours of admission. PMID- 3345026 TI - Single-dose oral phenytoin loading for uncomplicated patients. PMID- 3345027 TI - Advocating single-dose phenytoin loading. PMID- 3345029 TI - Radiography of lead paint. PMID- 3345028 TI - Temperature determination during CPR. PMID- 3345030 TI - Cyanide poisoning and the anion gap. PMID- 3345031 TI - Cryptococcal meningitis and AIDS. PMID- 3345032 TI - Lung macrophages: how many kinds are there? What do they do? PMID- 3345033 TI - Role of intracellular glycerol-3-phosphate in the synthesis of phosphatidylglycerol by freshly isolated adult rat alveolar type II cells. AB - Synthesis of phosphatidylglycerol and phosphatidylinositol, phospholipid components of pulmonary surfactant, use the same precursor, CDP-diacylglycerol. In alveolar type II epithelial cells, extracellular myoinositol has been used to suppress phosphatidylglycerol synthesis, presumably by competing with glycerol-3 P for a common pool of CDP-diacylglycerol. We sought to see if extracellular lactate would increase acetate incorporation into phosphatidylglycerol by increasing glycerol-3-P. Lactate and 10 mM cytidine increased acetate incorporation into phosphatidylglycerol, whereas myoinositol and pyruvate decreased acetate incorporation into phosphatidylglycerol. Lactate increased the intracellular content of glycerol-3-P. We conclude that phosphatidylglycerol synthesis can, in part, be regulated by intracellular glycerol-3-P concentration, and we speculate that extracellular (alveolar) lactate may increase glycerol-3-P concentration in alveolar type II cells in vivo. PMID- 3345034 TI - Histochemical and immunocytochemical identification of alveolar type II epithelial cells isolated from fetal rat lung. AB - Primary cultures of epithelial cells isolated from organotypic cultures of fetal (Days 18 through 22) rat lung have been characterized by histochemical and immunocytochemical parameters. Immunocytologic analysis with monoclonal antibodies to cytokeratins and with those to adult type II cells (JBR-1) demonstrated that the cell cultures were composed almost entirely of epithelial type II cells. Additional evidence that the cultures had the type II phenotype was obtained by Maclura pomifera lectin binding studies and by positive immunocytochemical demonstration of surfactant apoproteins. Comparison of cell cultures established from fetal lung at the early canalicular and saccular stages of rat lung development revealed that early fetal type II cells (Day 19) contained much glycogen and few lamellar bodies. The reverse was observed in type II cells isolated from fetal lungs at 21 days of gestation. Immunohistochemically determined surfactant apoproteins showed a similar developmental pattern to lamellar bodies. The cell cultures exhibited alkaline phosphatase activity, but this did not increase with development. Administration of dexamethasone to pregnant rats at 19 days gestation resulted in a significant loss of glycogen from fetal type II cells isolated 24 h later. This decrease in glycogen content was accompanied by an increase in the number of cells containing lamellar bodies. These findings indicate that freshly isolated fetal type II cells retain the morphologic features of the type II cells in vivo and provide a good system for the study of biochemical events occurring in these cells during specific stages of lung development. PMID- 3345035 TI - Existence of leukotoxin 9,10-epoxy-12-octadecenoate in lung lavages from rats breathing pure oxygen and from patients with the adult respiratory distress syndrome. AB - Pulmonary influxed neutrophils have been suggested to be involved in the development of hyperoxia-induced lung injury. We recently revealed that a highly toxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized by human neutrophils, thus it was named leukotoxin. Because hyperoxia-induced lung injury is a model of adult respiratory distress syndrome (ARDS), this study was designed to investigate whether or not leukotoxin is involved in the genesis of pulmonary oxygen toxicity and ARDS. After exposure to hyperoxia for 60 h, rats showed acute pulmonary edema, which was evidenced by increased lung weight, albumin concentrations, and angiotensin-converting enzyme (ACE) activities in lung lavages. These changes were correlated with an increased number of neutrophils. We detected leukotoxin in lung lavages of rats after exposure to hyperoxia for 60 h by high performance liquid chromatography and gas-chromatography/mass spectrometry. After intravenous injection of leukotoxin (100 mumol/kg) to rats, acute edematous lung injury occurred showing increases in lung weight, lung lavage albumin concentrations, and lung lavage ACE activities. In the lung lavages obtained from 5 patients with ARDS, significant increases in albumin concentrations and ACE activities were observed compared with those from subjects without pulmonary disease. Moreover, considerable amounts of leukotoxin, 38.5 +/- 21.9 nmol/lung lavage, were observed in the lavages from patients with ARDS. These findings suggest that leukotoxin plays an important role in the genesis of acute edematous lung damage in pulmonary oxygen toxicity, and that leukotoxin also links with the development of lung injury observed in patients with ARDS. PMID- 3345036 TI - Development of a prolonged eosinophil-rich inflammatory leukocyte infiltration in the guinea-pig asthmatic response to ovalbumin inhalation. AB - Considerable attention has recently focused on the role of inflammation in the pathophysiology of asthma, with special emphasis on "late-phase" bronchoconstriction and increased airway hyperreactivity after antigen challenge in sensitized subjects. The present report describes the histopathologic changes in guinea-pig lung and trachea at various time intervals after ovalbumin inhalation in nonsensitized (control) and sensitized animals. Bronchoalveolar lavage (BAL) was also used to assess the accompanying accumulation of intraluminal leukocytes. A distinct leukocyte margination, consisting of neutrophils and eosinophils, was observed in the peribronchial vasculature as early as 8 min postchallenge in sensitized guinea pigs. At 6 h, the eosinophils predominated and migrated to the peribronchiolar smooth muscle layer. Between 6 h and 18 h, eosinophils were seen in tracts between the smooth muscle cell layers, accumulating in large numbers in the bronchial mucosal epithelium. This pattern persisted for at least 7 days postchallenge during which eosinophils remained the dominant cell type present. Peribronchiolar accumulation of neutrophils and mononuclear cells was minimal at all time points studied. Intraluminal mucus eosinophilia developed between 18 h and 7 days. A similar pattern of eosinophil infiltration was observed in the tracheal epithelium. Control, nonsensitized, guinea-pig lungs showed minor changes with little or no eosinophil infiltration at any time after antigen challenge. These findings correlated well with the BAL study in which sensitized guinea pigs exhibited a marked delayed increase in eosinophil counts between 18 h and 7 days compared with that in nonsensitized animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345037 TI - Early and late-phase bronchoconstriction after allergen challenge of nonanesthetized guinea pigs. I. The association of disordered airway physiology to leukocyte infiltration. AB - We describe a guinea pig model of asthma in which animals were sensitized and challenged by inhalation of aerosolized ovalbumin. Challenge was performed under cover of mepyramine (10 mg/kg) to allow a high enough concentration of ovalbumin to elicit consistent late responses. Airway resistance and thoracic gas volume of conscious guinea pigs was assessed by whole body plethysmography before and at regular intervals for as long as 72 h after challenge. At the same time points, cellular changes in the lung were assessed by both examination of cells recovered by bronchoalveolar lavage (BAL) and lung histology. There were no significant changes in specific airway conductance (SGaw), BAL cell content or lung histology in animals challenged with saline control. Challenge with 2% ovalbumin caused an early fall in SGaw, which peaked at 2 h and amounted to a 43.7 +/- 4.1% fall from baseline. This was followed by 2 late responses, the first reaching maximum at 17 h with a 46.9 +/- 4.5% decrease in SGaw from baseline and the second at 72 h with a 39.0 +/- 3.5% fall in SGaw. Examination of BAL fluid revealed a 7-fold increase in neutrophils at 6 h and a 17-fold increase at 17 h, after which numbers decreased to baseline. Eosinophilia developed more slowly, being insignificant at 6 h and 6-fold at 17 h; by 72 h, eosinophils constituted 48.9 +/- 6.9% of the total cells recovered. No changes in mononuclear cells or lymphocytes were observed. Histologic examination of the lung revealed a progressive eosinophil infiltration of the airways, but not alveoli or vascular bed. Electron microscopy showed degranulation of eosinophils recovered by BAL and discharge of mucus from goblet cells in the trachea. Because these changes are similar to those that occur after allergen challenge in human asthma, we suggest that this represents a useful animal model in which to study the mechanism of early and late bronchoconstriction responses. PMID- 3345038 TI - Increased procollagen III aminoterminal peptide-related antigens and fibroblast growth signals in the lungs of patients with idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder characterized by an increased density of inflammatory cells, fibroblasts, and collagen within the lung parenchyma. To gain insights into the mechanisms leading to the increased density of fibroblasts and altered collagen metabolism in the IPF lung, bronchoalveolar lavage fluid from normal subjects and patients with IPF or sarcoidosis was analyzed for (1) the presence of antigenic material related to the aminoterminal propeptide domain of type III procollagen, and (2) fibroblast growth-promoting activity in the extracellular milieu of the lower respiratory tract. Whereas bronchoalveolar lavage fluid (BALF) type III procollagen aminoterminal peptide-related antigen levels in 59 patients with sarcoidosis were similar to the levels of control subjects (p greater than 0.10), 31 patients with IPF had markedly increased levels (12-fold over controls; p less than 0.025, IPF versus controls; p less than 0.01, IPF versus sarcoidosis). Type III procollagen aminoterminal peptide-related antigen levels correlated with an increase in the ability of BALF to stimulate fibroblast proliferation (p less than 0.05). Furthermore, BALF from patients with IPF markedly stimulated human lung fibroblast proliferation in vitro (199% increase, p less than 0.01), whereas lavage fluid from patients with sarcoidosis and from control subjects did not. The enhanced fibroblast proliferation induced by IPF BALF occurred in the absence of serum and exogenous growth factors, suggesting that both competence- and progression-type growth factors were present in the lavage fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345039 TI - Heterogeneous proliferative characteristics of human adult lung fibroblast lines and clonally derived fibroblasts from control and fibrotic tissue. AB - Pulmonary fibrosis results from an altered deposition of collagen within the lung parenchyma. This alteration is likely the result of both increased fibroblast proliferation and abnormalities in fibroblast collagen metabolism. Although the development of pulmonary fibrosis is preceded by inflammatory events in the lung, it is unclear whether altered fibroblast behavior requires continuous exposure to inflammatory mediators or alternatively results from the emergence in the lung of fibroblast populations possessing characteristics such as to explain the abnormalities seen in pulmonary fibrosis. To examine the latter hypothesis, we have established a number of fibroblast cell lines from control (C) lung tissue as well as from tissue from patients with active pulmonary fibrosis (PF), and have examined their in vitro proliferative characteristics. Our data show that PF fibroblasts proliferate significantly faster compared to C fibroblasts under standard culture conditions. We have also examined the in vitro proliferative characteristics of a substantial number of clonally derived fibroblasts. We report that a marked heterogeneity exists in terms of proliferation and also that a small but significant number of fast-growing clones are present in panels of clones derived from fibrotic tissue. These data suggest that there exists in fibrotic tissue, clones of fibroblasts with intrinsic growth characteristics which could in itself explain the increased fibroblast proliferation seen in pulmonary fibrosis. The fibrotic clones may emerge as dominant in the fibrotic lung under conditions of injury and repair likely to favor the expansion of this phenotype. PMID- 3345040 TI - Idiopathic pulmonary fibrosis. Abnormalities in bronchoalveolar lavage fluid phospholipids. AB - Bronchoalveolar lavage has been used to sample cells and proteins in the distal lung. One of the major secretory products of the alveolar type II epithelial cells, pulmonary surfactant, can be recovered by lavage. Abnormalities in alveolar type II cells are found in biopsies of patients with idiopathic pulmonary fibrosis (IPF), and abnormalities of pulmonary surfactant phospholipids have been reported after diffuse lung injury in animals and in humans. Therefore, we questioned if abnormalities in lavage phospholipids might also occur in IPF, a chronic inflammatory disease of the alveolar epithelium and interstitium, and, if present, would these abnormalities reflect histopathologic changes or predict responsiveness to therapy. Fifteen untreated patients with IPF, diagnosed by open lung biopsy, were studied and were found to have less than half the amount of bronchoalveolar lavage phospholipid as that recovered from healthy volunteers (p less than 0.05). In addition, patients with IPF had a lower proportion of phosphatidylglycerol and a higher proportion of phosphatidylinositol in the recovered phospholipids than did healthy volunteers (p less than 0.05). The severity of these alterations in phospholipid composition correlated with more advanced fibrotic histopathologic changes. Patients with less depression of total phospholipids in lavage improved with corticosteroid therapy, whereas the patients with more severely decreased total phospholipid recovered in lavage did not. PMID- 3345041 TI - Nasal provocation with bradykinin induces symptoms of rhinitis and a sore throat. AB - Kinins are generated in nasal secretions during allergic reactions and during induced rhinovirus colds. To determine if kinins may contribute to the symptomatology of these inflammatory reactions, 8 subjects were challenged with increasing doses of bradykinin or with placebo. Levels of albumin, histamine, and N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase were measured in nasal lavages, and symptom scores were noted. No symptoms or increases in mediators or protein were observed after placebo challenge. Symptom scores increased in a dose dependent manner, however, in response to bradykinin challenge. Increased symptoms were associated with significant increases in albumin and TAME-esterase activity, but no increases in histamine were observed. Nasal conductance measurements confirmed that bradykinin induces dose-dependent unilateral obstruction in the challenged nostril. Other common symptoms were rhinorrhea and, of particular relevance to rhinovirus infections, a persistent sore throat. We conclude that bradykinin causes increased vascular permeability and rhinitis, which are independent of mast cell mediator release. Kinins may, therefore, contribute to the symptomatology of inflammatory reactions of the upper airways, including the common cold. PMID- 3345042 TI - Local cellular and humoral responses to antigenic and distilled water challenge in subjects with allergic rhinitis. AB - We studied nasal responses to allergen, saline, and distilled water aerosol in 7 subjects with allergic rhinitis to determine whether they caused a similar release of mediators and influx of inflammatory cells into the nasal lumen. The subjects were challenged first with allergen and then with aerosols of distilled water and of normal saline in random order on separate days. We measured nasal airway resistance (Rn) by posterior rhinomanometry, measured the concentrations of protein, histamine, leukotrienes (LT) B4, C4, and D4, and platelet-activating factor (PAF-acether) and performed total and differential cell counts in nasal lavage fluid obtained before and after each challenge. Allergen challenge provoked a 2-fold or greater increase in nasal airway resistance in all subjects (mean increase = 12.2-fold). This response was associated with significant increases in protein, histamine, LTB4, and sulfidopeptide leukotrienes. 2-lyso PAF-acether increased significantly, indicating activation of phospholipase A2, but PAF-acether was detected in only one subject. The total cell count increased from 55 +/- 44 x 10(3)/ml to 200 +/- 168 x 10(3)/ml; polymorphonuclear neutrophils increased from 11 +/- 22 x 10(3)/ml to 108 +/- 96 x 10(3)/ml, and eosinophils increased from 1.3 +/- 1.8 x 10(3)/ml to 10.6 +/- 15.3 x 10(3)/ml (p less than 0.05). Saline insufflation provoked insignificant changes in mean Rn, in the levels of protein and all inflammatory mediators, and in the number and types of cells in nasal lavage fluid. Distilled water insufflation also provoked an insignificant increase in mean Rn, but there was a 14-fold increase in one subject.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345043 TI - Effect of laryngeal anesthesia on pulmonary function testing in normal subjects. AB - Pulmonary function tests (PFT) were performed on 11 normal subjects before and after topical anesthesia of the larynx. The PFT consisted of flow volume loops and body box determinations of functional residual capacity and airway resistance, each performed in triplicate. After the first set of tests, cotton pledgets soaked in 4% lidocaine were held in the pyriform sinuses for 2 min to block the superior laryngeal nerves. In addition, 1.5 ml of 10% cocaine was dropped on the vocal cords via indirect laryngoscopy. PFT were repeated 5 min after anesthesia. Besides routine analysis of the flow volume loops, areas under the inspiratory (Area I) and expiratory (Area E) portions of the loops were calculated by planimetry. Area I, peak inspiratory flow (PIF), as well as forced inspiratory flow at 25, 50, and 75% forced vital capacity (FVC), decreased after anesthesia. Peak expiratory flow decreased after anesthesia, but Area E and forced expiratory flow at 25, 50, and 75% FVC were unchanged. This protocol also was performed in 12 normal subjects with isotonic saline being substituted for the lidocaine and cocaine. In this group, no significant differences were observed when flow volume loop parameters were compared before and after topical application of saline. In 5 spontaneously breathing anesthetized dogs, posterior cricoarytenoid muscle and afferent superior laryngeal nerve activity were recorded before and after laryngeal anesthesia performed with the same procedure used in the human subjects. Laryngeal anesthesia resulted in a substantial decrease or a complete disappearance of afferent SLN activity recorded during unobstructed and obstructed respiration. The data suggest that laryngeal receptors help modulate upper airway patency in man. PMID- 3345044 TI - Dyspnea and diaphragmatic fatigue in patients with chronic obstructive pulmonary disease. Responses to theophylline. AB - This study sought answers to 2 questions: (1) Is severe dyspnea to the point of exhaustion regularly accompanied by diaphragmatic fatigue in patients with moderately severe chronic obstructive pulmonary disease (COPD)? (2) When diaphragmatic fatigue occurs in such patients, does theophylline prevent or delay its onset? Eight eucapnic patients with moderately severe COPD were subjected to 2 different stresses to the point of severe dyspnea requiring cessation of the stress. The stresses were cycle exercise and inspiratory resistive breathing, the latter requiring a tidal Pdi equal to 60% of Pdimax. Despite incapacitating dyspnea, objective evidence of diaphragmatic fatigue was not encountered during cycle exercise. During inspiratory resistive breathing, diaphragmatic fatigue was encountered in all patients as defined by consistent inability to attain a target Pdi during final moments of the resistance run. Patients were uniformly extremely dyspneic at this point. In neither stressful maneuver did oral sustained-release theophylline show a convincing or significant advantage over placebo when administered in a randomized double-blind crossover protocol. These results suggest that the diaphragmatic fatigue encountered in this sort of COPD patient may be of predominantly central rather than peripheral (myogenic) origin and that theophylline may not be effective in this type of fatigue. PMID- 3345045 TI - Rib cage and abdominal volume displacements during breathing in pregnancy. AB - To examine the effect of abdominal distension upon the actions of both rib cage and abdomen, we made serial determinations of tidal volume with a chest wall volume-displacement method in 8 pregnant women. Enhancement of tidal volume, long recognized in pregnancy, was achieved usually by augmentation of rib cage volume displacement. By contrast, abdominal volume displacement during quiet breathing is not altered in a predictable fashion by the gravid state. Given these findings, we hypothesize that the increased diaphragmatic contraction of pregnancy is accompanied by the transmission of that force to the lower rib cage via the area of apposition and that diaphragmatic contraction accounts for enhancement of the tidal breath. Diminished abdominal compliance might contribute to the augmentation of rib cage volume displacement as well. Konno-Mead diagrams suggest that this hypothesis is true in some, but not all, subjects. PMID- 3345046 TI - Respiratory muscle weakness associated with cerebellar atrophy. AB - Transdiaphragmatic pressures were measured in 3 patients with cerebellar atrophy. Recordings were made during 3 types of voluntary maneuver--maximal sniffs, full inspirations, and maximal static inspiratory efforts, and during bilateral supramaximal phrenic nerve stimulation at 1 Hz. Although diaphragmatic weakness was demonstrated during the voluntary maneuvers, transdiaphragmatic pressures recorded during phrenic nerve stimulation were normal. These findings indicate that diaphragmatic dysfunction, probably caused by ataxia during voluntary maneuvers, may occur in association with cerebellar atrophy. In the presence of diaphragmatic weakness, normal values of transdiaphragmatic pressure during phrenic nerve stimulation may suggest an upper motor neuron lesion affecting the diaphragm. PMID- 3345048 TI - Sampling technique and rheology of human tracheobronchial mucus. AB - The aims of this work were: (1) to establish a technique for the sampling of human tracheobronchial mucus not contaminated by saliva or topical anesthesia, and (2) to measure its viscoelastic properties. After local anesthesia of the hypopharynx by topical application of 4% xylocaine, a double-sleeve microbiology specimen brush was introduced into a flexible bronchoscope placed in the trachea. The brush was left in direct contact with the bronchial mucosa for 20 to 30 s to allow mucus to collect on it. The mucus sample was then scraped from the brush and immediately covered with paraffin oil. Its viscoelastic properties were determined by the magnetic microrheometer technique. Excluding the time to anesthetize, the whole procedure took less than 1 min (thus minimizing the effect of cough) and resulted in sufficient mucus for rheologic analysis in approximately 90% of trials, i.e., 2.1 +/- 1.5 (SD) mg. Mucus specimens were collected from 20 fasting healthy nonsmoking subjects; 17 of them returned for a second collection several days later. Values for mucus mechanical impedance (vector sum of elasticity and viscosity) at 1 rad/s were: Control 1, 141 +/- 41 (SE); Control 2, 155 +/- 58 dyn/cm2. There was a large variation in mucus viscoelasticity, both between subjects (CV, 130%) and within the same subject (CV, 55%) on different days. In 7 subjects, mucus samples were collected 15 min after intravenous injection of 0.6 mg atropine. Viscoelasticity in these samples was 708 +/- 147 dyn/cm2, a value significantly different from Control 1 (p less than 0.05) and Control 2 (p less than 0.05) values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345047 TI - Diaphragm function after pulmonary resection. Relationship to postoperative respiratory failure. AB - We studied the lung mechanics and respiratory muscle function in 20 patients undergoing pulmonary resection. Transdiaphragmatic pressure (delta Pdi) during quiet breathing did not show any remarkable change after the operation (9.5 +/- 1.1 to 10.9 +/- 1.0 cm H2O), while the ratio of abdominal to transdiaphragmatic pressure changes (delta Pab/delta Pdi) revealed a significant difference between the preoperative and the early postoperative periods (0.32 +/- 0.06 to 0.00 +/- 0.11, p less than 0.05). The postoperative delta Pab/delta Pdi correlated significantly with the work of breathing (r = -0.60, p less than 0.01). The maximal transdiaphragmatic pressure (Pdimax) decreased significantly after operation (75.0 +/- 15.8 to 32.8 +/- 12.4 cm H2O, p less than 0.05), with no significant change in the maximal inspiratory mouth pressure (MIP) (74.2 +/- 16.8 to 39.5 +/- 11.6 cm H2O). Four of 20 patients developed respiratory failure postoperatively and required mechanical ventilation. delta Pab/delta Pdi in these patients was significantly lower than in the other patients (-0.62 +/- 0.24 versus 0.16 +/- 0.09, p less than 0.005). Our results suggested that during quiet breathing diaphragmatic function was preserved and intercostal/accessory muscles recruitment increased, but maximal strength of the diaphragm might be reduced in patients undergoing pulmonary resection. PMID- 3345049 TI - A mouse model of the recrudescence of latent tuberculosis in the elderly. AB - The present study was designed to attempt to construct an animal model of the recrudescence of pulmonary tuberculosis by following the course of infection in mice exposed at 3 months of age to a low dose aerosol of Mycobacterium tuberculosis Erdman. The results show that such mice died of overwhelming lung disease at a median age of 24 months; in contrast, uninfected mice lived 4 to 6 months longer. Examination of infected mice over the period of 20 to 24 months of age provided evidence to suggest that recrudescence over this period of time was a general phenomenon within the infected mice, and was characterized by increases in lung bacterial numbers from approximately 10(4) to 10(8) organisms per animal. Experiments designed to investigate the underlying basis of this recrudescence revealed that the capacity of the old mice to mount acquired immunity to the infection exhibited a substantial age-related decline in these animals when compared with young mice exposed to similar aerogenic doses. The data suggest, therefore, that "spontaneous" recrudescence of pulmonary tuberculosis in old mice reflects their inability to recall anamnestic acquired immunity to the reemerging infection. PMID- 3345051 TI - NHLBI workshop summary. Postnatal lung development in health and disease. PMID- 3345050 TI - The effect of aerosolized verapamil on the response to isoproterenol in asthmatics. AB - Calcium antagonists, like verapamil, may play a beneficial role in the management of airway disease. However, the effect that verapamil plays in modulating the response to beta-adrenergic bronchodilator therapy has not been well characterized. We found that inhaled verapamil, 3 mg, had little effect on the bronchodilator response to sequential inhalations of isoproterenol. Also, verapamil had no significant effect on isoproterenol's protection against methacholine-induced bronchospasm in a group of 8 mild asthmatics. These studies support the safe use of these agents in combination but do not demonstrate any additive or synergistic benefit. PMID- 3345052 TI - Lung water measurement in intensive care units. PMID- 3345053 TI - A computerized recall system for clinical trials. AB - A major difficulty facing investigators involved in clinical studies is ensuring the timely follow-up of patients involved in the investigations. Two microcomputer programs are described that create a follow-up calendar for each subject, list patients due to appear for any given month, and generate printouts of subjects who have missed key follow-up appointments. These programs were formulated using dBASE II (Ashton Tate, California), a widely used data base management package suitable for International Business Machines-compatible microcomputers. The programming concept used in formulating these programs can be adapted to most other data base management software systems. These programs are currently enhancing the follow-up of patients enrolled in a prospective ophthalmic surgical protocol and are potentially useful to any investigator involved in prospective studies who has access to a microcomputer. PMID- 3345054 TI - Diffuse midperipheral acute retinal pigment epitheliopathy. AB - We examined a 16-year-old boy with a remarkable decrease in vision OS. Typical lesions of acute retinal pigment epitheliitis (Krill's disease) were not present in the macula but were diffuse in the midperiphery. Angiographic findings were similar to those in Krill's disease. The left fundus returned to normal two weeks later, but ten months passed before electro-oculography, light sensitivity, and dark adaptation were normal. Thus, there may be two types of acute retinal pigment epitheliitis: one is Krill's disease, and the other is a vast disturbance in the retinal pigment epithelium. PMID- 3345055 TI - A-pattern esotropia with bilateral inferior oblique muscle overaction. AB - An eight-year-old boy with residual congenital esotropia, with an A-pattern and overacting inferior obliques is described. Unilateral medial rectus maximal recession and insertion supraplacement, combined with bilateral inferior oblique myectomies resulted in disappearance of the A-pattern. This is the fourth reported case of A-pattern esotropia with overacting inferior obliques. Factors related to horizontal rectus muscle function in up- and down-gazes may explain the pattern seen in this, and similar cases. PMID- 3345056 TI - Systemic effects of intraocular epinephrine during cataract surgery. AB - This paper examines the effects of intraocular epinephrine on systemic blood pressure and heart rate during cataract surgery. Sixty-two patients were studied, all of whom received an intraocular infusion of approximately 200 to 300 mL of balanced salt solution with 0.5 mL of epinephrine 1:1000. There was no statistically significant change in blood pressure or heart rate during the time of epinephrine administration. Electrocardiogram monitoring during surgery showed no changes. We believe that dilute concentrations of epinephrine administered during extracapsular cataract extraction pose little threat of systemic toxicity. PMID- 3345057 TI - Argon peripheral iridotomy and cataract formation. AB - The records of 74 patients with primary angle-closure glaucoma were reviewed. Cataract formation in 103 eyes treated with argon laser were compared with eyes in an age- and sex-matched, randomly-selected control group to determine whether cataract formation was hastened by laser iridotomy. Twenty-three percent of eyes in the study group showed development of cataracts 29.9 months after laser treatment. This did not differ from the incidence of cataract formation (20%) in the same group before laser exposure (P = .357) and was significantly lower than the 49% incidence of cataracts observed in the age-matched control group (P less than .001). These data demonstrate the safety of laser iridotomy in the treatment of narrow-angle glaucoma. PMID- 3345058 TI - Repair of avulsion of eyelids and cheek. AB - Our patient was thrown through the roof of a soft-top Jeep. The right upper and lower lids and the cheek were separated completely from their attaching structures and were hinged laterally over the zygomatic arch. The patient had normal extraocular rotations but could not see when the face flap was replaced. Steps in repair of these separated structures are described. A satisfactory cosmetic and functional result was achieved by anatomic reconstruction. Ptosis surgery at a later date was necessary to give a more normal appearance. PMID- 3345059 TI - Results of pars plana vitrectomy in Behcet's disease. AB - The result of pars plana vitrectomy in Behcet's syndrome has been investigated in patients with vitreous hemorrhage and condensation. Surgery was performed in seven cases. All of the patients became more hypotonic after surgery, and phthisis developed in less than two years. It is suggested that pars plana vitrectomy should not be performed in Behcet's patients. PMID- 3345061 TI - [Aneurysm of the inferior mesenteric artery]. AB - Aneurysm of the inferior mesenteric artery is rare. Often unrecognized unless complicated, it is, today, demonstrated by sonography or tomodensitometry and confirmed by angiography. Usually observed in patients with atheroma, it presents a mechanical origin secondary to a "jet disorder" phenomenon occurring in an artery with a hyper-output, responsible for almost the entire gastro-intestinal vascularization. The prevention of its dangerous complications (rupture or thrombosis) justifies a systematic procedure usually requiring, in addition to the excision of the aneurysm, a revascularization of the digestive arteries, as in the case presented here. PMID- 3345060 TI - [Magnetic resonance imaging in the diagnosis of myxedematous pericardial effusions]. AB - Two cases of myxedematous pericardial effusions studied by magnetic resonance imaging (MRI) are reported. After a reminder of the place of pericardial involvement in this disease, the advantage of MRI which provides original semiologic factors on the analysis of topographic extension and on the approach of the cellular characteristics of the effusion, is presented. Concerning the latter, difficulties of interpretation and current imprecisions are discussed but we will especially remember the advantage of this recent technique in the diagnosis of an effusion, even moderate, in hypothyroidism, mainly in patients with poor sonographic response. PMID- 3345062 TI - [Intensive cardiac care unit. Values and limitations. Apropos of 202 consecutive admissions]. AB - In order to specify the contribution of this specialized structure, 202 consecutive patients hospitalized in cardiac care unit, were systematically studied. All specialized procedures (S, P), defined as specific to this unit, have been considered with their results, taking into account the type of underlying pathology. Age and sex are factors in the effectiveness of SP. Complicated myocardial infarction requires the most SP (2.9 SP/person, in an average) with good results in approximately 50 p. cent. Left ventricular insufficiency requires two SP/patient, with good results in approximately 81 p. cent. On the contrary, unstable angina, arrhythmias and/or conduction disorders where post-operative monitoring requires less procedures (approximately one per patient), but a constant effectiveness. Uncomplicated myocardial infarction seems to represent the least indication of the CCU, in so far as only 0.3 SP/patient are performed, and that this pathology represents only 14 p. cent of admissions. But, among these patients, 100 p. cent of those who undergo SP, derive benefit from it. On the contrary, cardiogenic shock complicating a myocardial infarction, anterior most of the time, requires a great deal of SP, but with an almost insignificant benefit. They present the difficult problem of their direction toward this type of structure. It is therefore desirable to weigh advantages and drawbacks, as much for the patient as for the community which supports the economical burden of this structure, knowing that it always remains an individual decision. PMID- 3345063 TI - Eye movements, EEG, and fatal anoxic coma. PMID- 3345064 TI - Absence of complement activation in demyelinating polyradiculoneuropathies. PMID- 3345065 TI - Inverse/reverse ocular bobbing. PMID- 3345066 TI - Familial Alzheimer's disease in American descendants of the Volga Germans: probable genetic founder effect. AB - Five families are described in which autopsy-confirmed presenile Alzheimer's disease (AD) has occurred in men and women over multiple generations consistent with autosomal dominant inheritance. All 5 families are descendants of a group of immigrants known as the Volga Germans who came to the United States between 1870 and 1920. Their ancestors moved from Germany to the southern Volga region of Russia in the 1760s. All 5 American families are descendants of persons originally living in two small adjacent Volga German villages and share several surnames known to have been present in the census records of those villages. Although a single affected common ancestor cannot be identified, it is likely that the AD in these families represents an autosomal dominant gene inherited from one ancestor (the founder effect). This information is of importance in the genetic study of AD in these families because it greatly increases the probability of genetic homogeneity. There are more than 300,000 American descendants of the Volga Germans, and the prevalence of AD has never been studied in this population. PMID- 3345067 TI - Neurological complications of human immunodeficiency virus infection in patients with lymphadenopathy syndrome. AB - To determine if there is a relationship between neurological abnormalities and human immunodeficiency virus (HIV) infection in patients with lymphadenopathy syndrome (LAS), we studied 39 homosexual/bisexual men with LAS (mean duration of LAS, 4.1 years) and 38 homosexual/bisexual men who were seronegative for HIV (controls). Six LAS patients had histories of symptoms suggesting mononeuropathy, 9 had symptoms suggesting distal symmetrical polyneuropathy, and 9 had histories of herpes zoster radiculitis. Overall, significantly more LAS patients (18) than controls (3) had histories of symptoms or signs of neurological abnormality (odds ratio, 10.0; p = 0.0003). By neuropsychological assessment, 9 of 18 LAS patients and 2 of 26 controls were abnormal (odds ratio, 12.0; p = 0.004). Of those abnormal on the neuropsychological assessment, the majority scored in the mildly impaired range. Magnetic resonance imaging was abnormal in 1 LAS patient and in 1 control. Neither neurological nor neuropsychological abnormalities correlated with duration of LAS, absolute T-helper lymphocyte count, or T-helper/T suppressor lymphocyte ratio. These results indicate an association of neurological and neuropsychological abnormalities with HIV in patients with LAS. They suggest that mild neurological abnormalities in LAS are common and that HIV may directly or indirectly be the cause. PMID- 3345068 TI - Dystonia in Parkinson's disease: clinical and pharmacological features. AB - We studied the features of dystonia in 9 patients with untreated idiopathic Parkinson's disease and in 56 patients on sustained treatment with L-dopa. Dystonia was seen as an initial symptom in patients with both early- and late onset Parkinson's disease and included action dystonia of the limbs and cranial dystonia. Although the coexistence of parkinsonism and dystonia suggests a common pathophysiology, antiparkinsonian drugs did not consistently influence dystonic spasms. L-dopa-induced dystonia was seen as an off-period, biphasic, or peak-dose phenomenon. Each type showed a distinctive pattern of localization of dystonic spasms, possibly reflecting neurochemical aspects of basal ganglia somatotopy. Neuropharmacological studies performed in 12 patients suggest that off-period dystonia is genuinely induced by L-dopa and best relieved by antiparkinsonian agents. PMID- 3345069 TI - Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update. AB - Chiasmatic/hypothalamic gliomas (CHG) of childhood may cause progressive neurological and visual deterioration. Radiotherapy results in at least transient stabilization of tumor growth in most patients but may also have adverse long term effects, especially in young children. Since 1977, children with progressive CHG under 5 years of age at diagnosis have been treated with combination chemotherapy (actinomycin D and vincristine) without radiotherapy. Twenty-four patients, a median of 1.6 years of age at diagnosis, have been treated and followed for a median of 4.3 years (range, 0.3-10 years). All patients are alive. Nine have developed radiographic or clinical progression, occurring a median of 3 years (range, 2-6.5 years) after initiation of treatment. Fifteen of 24 (62.5%) have remained free of progressive disease and have received no other therapy. Tumor shrinkage was documented in 9 of 24 patients but did not clearly relate to long-term outcome. Full-scale intelligence quotient (IQ) obtained a median of 3.5 years after diagnosis in patients who received only chemotherapy was a mean of 103 (range 84-133). We conclude that chemotherapy can significantly delay the need for radiotherapy in children with CHG and such a delay may be beneficial regarding long-term outcome. PMID- 3345070 TI - Selective brainstem injury in an asphyxiated newborn. AB - We report the clinical, radiological, and neuropathological features of selective brainstem injury in an asphyxiated term infant. Disproportionate injury to thalamus, basal ganglia, and brainstem with relative sparing of cortex and subcortical white matter is observed occasionally after acute total asphyxia. Although this entity has been well documented neuropathologically, the specific computed tomographic findings have not been reported previously to our knowledge, and the clinical correlation is recognized rarely. PMID- 3345072 TI - Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients. AB - We conducted a double-blind pilot study of 8 patients with established cerebral infarction to evaluate the effect of a single dose of amphetamine on recovery of motor function using the Fugl-Meyer scale. Four patients received amphetamine; the rest were given placebo. All underwent a session of physical therapy. Patients treated with amphetamine obtained greater increments in motor scores than the controls. Along with animal studies, these findings may allow the development of a pharmacological approach to stroke rehabilitation. PMID- 3345071 TI - Prospective nerve conduction studies in cisplatin therapy. AB - We studied nerve conduction prospectively in 38 women receiving cisplatin for gynecological malignancies. Decreased sensory nerve action potential amplitudes and prolonged sensory latencies were the only significant changes identified. This prospective electrophysiological study validates the clinical observation of frequent sensory symptoms and occasional sensory neuropathies associated with cisplatin therapy. PMID- 3345073 TI - Measurement of live bacteria by Nomarski interference microscopy and stereologic methods as tested with macroscopic rod-shaped models. AB - A new method is proposed to measure bacterial cells under growth conditions. Bacterial cells, suspended in their growth medium, were attached to a cover slip with poly-L-lysine. The cover slip was inverted and placed on a glass microscope slide. To prevent dehydration of the medium, the edges of the cover slip were sealed to the microscope slide with clear fingernail polish. The bacteria on the slide were then quickly photographed with a Leitz light microscope, using Nomarski optics. The photographic negatives were then projected at a standard distance through a lens system, and the projected images of the whole cells were outlined by hand onto graph paper. The profile images so transcribed onto the graph paper were in effect transverse sections of each of the cells. Using stereologic grid and point counting techniques, the area of the cell transverse section as well as the perimeter or circumference of the transverse section were estimated. Formulae were developed so that both the volume and surface area of the whole cell could be ascertained from these area and circumference measurements. Since the efficacy of any measurements of surface area and volume of microscopic rod-shaped bacterial cells could be questioned, macroscopic rod shaped models were used to test the theory and formulae and to compare this method with other commonly used cell-sizing techniques. This technique could be used in any study of bacterial cell size or changes in cell size (e.g., osmotic shifts). PMID- 3345074 TI - Capacity of aquatic bacteria to act as recipients of plasmid DNA. AB - A total of 68 gram-negative freshwater bacterial isolates were screened for their ability to receive and express plasmids from Pseudomonas aeruginosa donors. The plate mating technique identified 26 of the isolates as recipient active for the self-transmissible wide-host-range plasmid R68; 10 were recipient active by R68 mobilization for the wide-host-range plasmid cloning vector R1162. Frequencies of transfer were compared by using three conjugal transfer procedures: broth, plate, and filter mating. For every recipient tested, a solid environment was superior to a liquid environment for transfer. The broth mating technique failed to demonstrate R68 transfer in 63% of the recipient-active isolates. Filter mating, in general, yielded the highest transfer frequencies. The more-rapid plate mating procedure, however, was just as sensitive for testing the capacity of natural isolates to participate in conjugal plasmid transfer. PMID- 3345076 TI - A new selective medium for isolating Listeria spp. from heavily contaminated material. AB - Food-associated outbreaks of human listeriosis have emphasized the importance and necessity of screening food for the presence of Listeria isolates-selective agar medium combining acriflavine (10 mg/liter) with ceftazidime (50 mg/liter) was developed. A total of 1,099 cheese production specimens were cultured, from which 157 Listeria isolates. (14.3%) grew. When compared with modified McBride agar, the acriflavine-ceftazidime agar recovered more Listeria isolates (98 versus 65%, P less than 0.001) more rapidly (57% after 48 h of incubation of the enrichment broth versus 35%, P less than 0.01) and in greater amounts. Acriflavine ceftazidime selective agar medium proved to be a highly sensitive medium to recover Listeria spp. from heavily contaminated food products. PMID- 3345075 TI - Existence of a new type of sulfite oxidase which utilizes ferric ions as an electron acceptor in Thiobacillus ferrooxidans. AB - A new type of sulfite oxidase which utilizes ferric ion (Fe3+) as an electron acceptor was found in iron-grown Thiobacillus ferrooxidans. It was localized in the plasma membrane of the bacterium and had a pH optimum at 6.0. Under aerobic conditions, 1 mol of sulfite was oxidized by the enzyme to produce 1 mol of sulfate. Under anaerobic conditions in the presence of Fe3+, sulfite was oxidized by the enzyme as rapidly as it was under aerobic conditions. In the presence of o phenanthroline or a chelator for Fe2+, the production of Fe2+ was observed during sulfite oxidation by this enzyme under not only anaerobic conditions but also aerobic conditions. No Fe2+ production was observed in the absence of o phenanthroline, suggesting that the Fe2+ produced was rapidly reoxidized by molecular oxygen. Neither cytochrome c nor ferricyanide, both of which are electron acceptors for other sulfite oxidases, served as an electron acceptor for the sulfite oxidase of T. ferrooxidans. The enzyme was strongly inhibited by chelating agents for Fe3+. The physiological role of sulfite oxidase in sulfur oxidation of T. ferrooxidans is discussed. PMID- 3345077 TI - Aquatic nitrogen transformations at low oxygen concentrations. AB - Nitrite and nitrous oxide made up 40% of the hypolimnetic dissolved inorganic nitrogen in mesotrophic Lake Rotoiti, New Zealand, prior to hypolimnetic anoxia. Up to 120 mg of N m-3 as nitrite and 20 mg of N m-3 as nitrous oxide accumulated, whereas dissolved-oxygen concentrations remained between 1.0 and 0.2 g m-3 and were totally consumed when the hypolimnion became completely anoxic. Assays of water column nitrification potentials, together with measurements of the relative rates of nitrate and nitrite reduction, suggested that at low dissolved-oxygen concentrations both nitrite and nitrous oxide were produced mainly by ammonium oxidizing bacteria, with nitrous oxide being a product of nitrifier denitrification. PMID- 3345078 TI - Metabolism of 6-nitrochrysene by intestinal microflora. AB - Since bacterial nitroreduction may play a critical role in the activation of nitropolycyclic aromatic hydrocarbons, we have used batch and semicontinuous culture systems to determine the ability of intestinal microflora to metabolize the carcinogen 6-nitrochrysene (6-NC). 6-NC was metabolized by the intestinal microflora present in the semicontinuous culture system to 6-aminochrysene (6 AC), N-formyl-6-aminochrysene (6-FAC), and 6-nitrosochrysene (6-NOC). These metabolites were isolated and identified by high-performance liquid chromatography, mass spectrometry, and UV-visible spectrophotometry and compared with authentic compounds. Almost all of the 6-NC was metabolized after 10 days. Nitroreduction of 6-NC to 6-AC was rapid; the 6-AC concentration reached a maximum at 48 h. The ratio of the formation of 6-AC to 6-FAC to 6-NOC at 48 h was 93.4:6.3:0.3. Interestingly, compared with results in the semicontinuous culture system, the only metabolite detected in the batch studies was 6-AC. The rate of nitroreduction differed among human, rat, and mouse intestinal microflora, with human intestinal microflora metabolizing 6-NC to the greatest extent. Since 6-AC has been shown to be carcinogenic in mice and since nitroso derivatives of other nitropolycyclic aromatic hydrocarbons are biologically active, our results suggest that the intestinal microflora has the enzymatic capacity to generate genotoxic compounds and may play an important role in the carcinogenicity of 6 NC. PMID- 3345079 TI - Simple fluorescence method for rapid estimation of aflatoxin levels in a solid culture medium. AB - Aflatoxin concentrations in agar media were estimated with a direct technique that quantifies the fluorescence of agar containing aflatoxins. Tubes containing 5 ml of an agar medium inoculated with spores of aflatoxin-producing Aspergillus isolates were incubated for 3 days at 30 degrees C and set in a carriage specifically designed to carry culture tubes in a scanning densitometer. Fluorescence (450 nm and above) was elicited in the agar by UV light (365 nm) and photometrically measured. Agar fluorescence directly correlated (r2 = 0.89 +/- 0.05, P less than 0.001) with the concentration of aflatoxin within the range 0 to 18.7 micrograms/g. The lowest aflatoxin concentration detected was 50 ng/g. The technique successfully differentiated the aflatoxigenic potentials of Aspergillus isolates. PMID- 3345080 TI - Environmental factors affecting indole metabolism under anaerobic conditions. AB - The influence of physiological and environmental factors on the accumulation of oxindole during anaerobic indole metabolism was investigated by high-performance liquid chromatography. Under methanogenic conditions, indole was temporarily converted to oxindole in stoichiometric amounts in media inoculated with three freshwater sediments and an organic soil. In media inoculated with methanogenic sewage sludge, the modest amounts of oxindole detected at 35 degrees C reached higher concentrations and persisted longer when the incubation temperature was decreased from 35 to 15 degrees C. Also, decreasing the concentration of sewage sludge used as an inoculum from 50 to 1% caused an increase in the accumulation of oxindole from 10 to 75% of the indole added. Under denitrifying conditions, regardless of the concentration or source of the inoculum, oxindole appeared in trace amounts but did not accumulate during indole metabolism. In addition, denitrifying consortia which previously metabolized indole degraded oxindole with no lag period. Our data suggest that oxindole accumulation under methanogenic, but not under denitrifying conditions is caused by differences between relative rates of oxindole production and destruction. PMID- 3345081 TI - Topical minoxidil therapy for androgenetic alopecia. PMID- 3345082 TI - The retinoids and inflammatory bowel disease. PMID- 3345083 TI - Photosensitivity to methyldopa. PMID- 3345084 TI - Linear cutaneous lesions of Kaposi's sarcoma: a clinical clue to the diagnosis of acquired immunodeficiency syndrome. PMID- 3345085 TI - Cutaneous extramedullary hematopoiesis in a patient with acute myelofibrosis. PMID- 3345086 TI - Abnormal DNA ploidy in cells of the epidermis in a case of porokeratosis. PMID- 3345087 TI - Human immunodeficiency virus infection in the United States. PMID- 3345088 TI - Piebaldism. PMID- 3345089 TI - Optimal use of an occlusive dressing to enhance healing. Effect of delayed application and early removal on wound healing. AB - We examined the effect of delayed application and early removal of a polyurethane dressing on excisional wounds in swine. Backs of pigs were wounded with an electrokeratome, and wounds were divided into the following treatment groups: (1) air exposed; (2) dressings applied immediately after wounding and kept on until wounds were evaluated; (3) dressings applied immediately after wounding and removed at 6, 24, or 48 hours; and (4) dressings applied 2, 6, and 24 hours after wounding. Wounds were excised on days 3 through 7 and incubated in sodium bromide to allow separation of the epidermis and dermis. Specimens were considered healed if no defect was present. To promote optimal resurfacing in superficial wounds, polyurethane dressings need to be applied within two hours after wounding and should be kept in place for at least a 24-hour period. PMID- 3345091 TI - Osteomyelitis of the distal phalanges in three children with severe atopic dermatitis. AB - Three children with severe, secondarily infected atopic dermatitis since infancy developed osteomyelitis of the distal phalanges of the hands. The insidious onset of one or more distal subungual black macules was followed by edema, erythema, and pain in the involved fingers. No child had an elevated erythrocyte sedimentation rate or fever, but all had roentgenographic or scintigraphic evidence of bony destruction. In two children, Staphylococcus aureus grew from skin surface cultures; S aureus also grew from nail bed and osseous cultures of the distal phalanges; Streptococcus viridans grew from one child's nail bed. All children had prolonged hospitalizations. In two children, laboratory evaluation of immunologic function disclosed normal findings. We postulate that intense scratching of infected skin coupled with minor trauma to the fingertips created distal subungual microabscesses that spread contiguously to the underlying bone. PMID- 3345090 TI - Fine-needle aspiration biopsy of mycosis fungoides presenting as an ulcerating breast mass. AB - A patient with previously diagnosed Hodgkin's disease presented with ulcerating lesions on her scalp and breast. Fine-needle aspiration of the breast lesion revealed convoluted cells consistent with mycosis fungoides. Review of the patient's previously obtained lymph node biopsy specimens revealed a diagnosis of mycosis fungoides rather than Hodgkin's disease. Better communication between hospitals, pathologists, and clinicians may have prevented the erroneous original diagnosis of Hodgkin's disease in this patient. PMID- 3345092 TI - Reddish-brown macules with telangiectasia and pruritus. Urticaria pigmentosa telangiectasia macularis eruptiva perstans (TMEP) variant, with systemic mastocytosis. PMID- 3345093 TI - A subungual nodule of recent onset. Tungiasis. PMID- 3345095 TI - Calcium and the skin. PMID- 3345094 TI - Calf ulcer in an immunocompromised host. Cryptococcosis. PMID- 3345096 TI - Nutritional evaluation of patients on maintenance dialysis therapy. PMID- 3345097 TI - CAVH in pediatrics: meeting the challenge. PMID- 3345098 TI - Comparison stressors and quality of life of dialysis patients. PMID- 3345099 TI - Joint letter on occupational exposure to HBV and HIV. PMID- 3345100 TI - Nephrology nursing consult: Case study. Peritoneal dialysis in HIV positive patients. PMID- 3345101 TI - Evolution of a nephrology nurse. PMID- 3345102 TI - Theory, practice, and research in transplant nursing. PMID- 3345103 TI - Comparison of sleep in osteoarthritic patients and age and sex matched healthy controls. AB - A sleep laboratory comparison of the sleep of 14 osteoarthritic patients with that of 16 age and sex matched healthy controls was undertaken. After three nights of adaptation continuous recordings of electroencephalographic (EEG), electro-oculographic (EOG), and electromyographic (EMG) activity were obtained for the next two nights. A comparison of EEG sleep variables during this baseline period showed that osteoarthritic patients had a significantly greater percentage of stage 1 and significantly smaller percentage of stage 2 sleep than control subjects. These findings indicate sleep disturbance in osteoarthritic patients. The limited degree of disturbance observed in these patients may be due to the fact that they were allowed to continue with their normal anti-inflammatory and analgesic medication for the course of the study. PMID- 3345104 TI - Kinetic investigations into the possible cause of low serum histidine in rheumatoid arthritis. AB - To investigate the cause of low serum histidine in rheumatoid arthritis (RA) single oral and intravenous doses of L-histidine were administered to patients with active RA, and to an equal number of age and sex matched control subjects. In the first study 13 patients and their controls received a 100 mg kg-1 dose of L-histidine as an aqueous slurry. Significant differences were seen in body weight, predose baseline serum histidine concentration, Cmax, t1/2, and area under curve, AUC0-infinity. In a second study six patients and six controls each received a 50 mg kg-1 dose of L-histidine both orally and intravenously on two separate occasions. The patients with RA had a lower baseline serum histidine concentration, a lower volume of distribution, and a shorter plasma half life than the controls, but these differences were not statistically significant. No difference was seen in bioavailability or clearance. Low serum histidine in RA is unlikely to be due to malabsorption from the gut, uptake by abnormal gut flora, or increased metabolism. PMID- 3345105 TI - Sequential nailfold capillary microscopy in scleroderma and related disorders. AB - Sequential nailfold capillary microscopy was carried out monthly for seven months in seven patients (four with scleroderma, one with dermatomyositis, one with mixed connective tissue disease, and one with limited connective tissue disease). Progressive enlargement of some capillary loops was observed, with a number becoming obliterated, leaving avascular areas. Extravasation from capillaries usually preceded capillary loss. These observations have shown the progressive nature of the nailfold capillary abnormalities associated with these disorders and suggest that capillary enlargement is the result of injury, rather than compensation for capillary loss. PMID- 3345106 TI - Computed tomographic demonstration of calcification of the ligamenta flava of the lumbosacral spine in ankylosing spondylitis. AB - An axial computed tomographic (CT) scan of the lumbosacral regions was performed in 65 patients. The patient population was divided into two groups. The first (control) group included 40 elderly patients without calcification of the ligamenta flava. The second group included 25 patients with ankylosing spondylitis. More than 90% of those in the second group showed calcified lumbosacral ligamenta flava. In two patients these calcifications produced spinal stenosis. The diagnostic and practical importance of these findings are discussed. PMID- 3345107 TI - Low free testosterone levels in rheumatoid arthritis. AB - The androgen status of 25 male patients with rheumatoid arthritis (RA) was assessed and compared with that of age matched controls with osteoarthritis (OA). Significantly reduced levels of serum free testosterone were found in the RA group. Within that group free testosterone was unrelated to all indices of disease activity measured, though it was strongly related to latex positivity. These results support the hypothesis that male sex hormones may have a protective role in RA, though prospective studies would be necessary to determine whether the relation was one of cause or effect. PMID- 3345108 TI - Acute pancreatitis in systemic lupus erythematosus: report of a case unrelated to drug therapy. AB - Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease that can affect most organs or systems. It most frequently involves the joints, skin, and the kidneys. It less commonly involves the central nervous system, heart, and lungs. Acute pancreatitis in SLE is rare. It is usually mild, occurring in association with more severe organ involvement elsewhere. A patient with newly diagnosed SLE is reported who developed acute fulminant pancreatitis unrelated to concomitant drug therapy and who eventually died of complications including a systemic fungal infection related to this. PMID- 3345109 TI - Severe myalgia in familial Mediterranean fever: clinical and ultrastructural aspects. AB - Severe myalgia is an uncommon feature of familial Mediterranean fever (FMF). A patient is presented in whom acute myalgia and high fever were the sole clinical findings during an FMF attack. The ultrastructural picture of the muscle tissue during the acute stage was characterised by a large deposition of collagen fibrils. The myalgia subsided during colchicine treatment. The clinical and ultrastructural features of myalgia in FMF are discussed in the light of the relevant literature. PMID- 3345111 TI - A new mechanical device for circular compression anastomosis. Preliminary results of animal and clinical experimentation. AB - The authors report the preliminary results obtained in animal and clinical experimentation of a new mechanical device for circular anastomosis which they have developed. It is a gun that places an apparatus consisting of three polypropylene rings that, through the compression among them of the severed edges of the bowel, realize a sutureless anastomosis and are spontaneously evacuated. Fifty-eight colonic anastomoses were performed in dogs with this device; 23 stapled colonic anastomoses were also executed concurrently. Forty-four animals underwent a relaparotomy to remove the colonic specimen containing the anastomoses. Bursting pressure and the histologic features of the anastomoses were evaluated at different time intervals after operation. A good healing of all compression anastomoses was observed, thereby allowing them to initiate the experience in humans. Thirteen anastomoses (6 colorectal extraperitoneal, 1 colorectal intraperitoneal, 5 colocolonic, 1 ileorectal) were performed at the 1st Surgical Department, Milan University. One subclinical leakage (7.7%) spontaneously healed in a few days. No stenoses were observed. PMID- 3345110 TI - Villous tumors of the duodenum. AB - Records of 32 patients with 34 villous and tubulovillous adenomas of the duodenum, treated at the Cleveland Clinic over the past 21 years, were reviewed. Twenty-two patients (69%) had complete resection of the adenoma; the incidence of malignancy was 47%. Five patients underwent a Whipple procedure; 4 patients had segmental resection of the duodenum; 12 had wide local excision of the adenoma; 1 had both a segmental resection and a local excision for two separate adenomas; and 5 patients had endoscopic excision alone. The remaining five patients underwent exploratory laparotomy alone or with palliative bypass procedures. A 28% recurrence rate was observed, all of these after segmental resection, local excision, or endoscopic excision. The highest recurrence rate was associated with local excision. The 2- and 5-year survival rates for patients with adenomas containing invasive cancer were 22% and 0%, respectively, compared to 87% and 87%, respectively, for benign adenomas (including those with carcinoma in situ). Twenty-two per cent of patients had intestinal polyposis syndromes. Duodenal adenomas were diagnosed a mean of 17 years after colectomy for polyposis, indicating the need for continued surveillance in these patients. PMID- 3345112 TI - Pancreaticogastrostomy following pancreatoduodenectomy. AB - Operative death following pancreatoduodenectomy results essentially from a pancreatojejunal anastomosis leakage. Pancreaticogastrostomy has been used infrequently. Seventeen patients (12 with malignant tumors and 5 with chronic pancreatitis) have undergone pancreaticogastrostomy following pancreatoduodenectomy. There was no operative mortality rate and no pancreaticogastrostomy leakage. Our data agree with data concerning pancreaticogastrostomy published in literature; cumulative mortality rate including our results is 4.5% (6 out of 134 patients) with only one transient benign pancreatic fistula reported. Many advantages offered by this method can explain these positive results including trypsine neutralization by gastric acidity and the possibility of nasogastric aspiration on contact with the anastomosis. Furthermore, permeability of the pancreatic duct can be easily verified by endoscopic examination. However, external pancreatic insufficiency does not seem to occur in long-term follow-up. These results suggest that this simple and safe method merits a more widespread application. PMID- 3345113 TI - Pancreatitis in childhood. Experience with 49 patients. AB - Pancreatitis in children is not common but can be associated with severe morbidity rates. We have treated 49 children with pancreatitis over the past 12 years ranging in age from 1 month to 18 years. One third of the patients had biliary tract disease as an etiology, with nearly half of these being related to underlying hematologic disease, usually sickle cell anemia. Another third of the pancreatitis was due to trauma, and one third of these were related to child abuse. Other etiologies were systemic disease (6 patients), congenital anomalies (8 patients), and idiopathic (3 cases). Eighty-two per cent of the patients presented with abdominal pain, but four children, all less than 4 years old, presented with an abdominal mass. Twenty-nine patients required 33 operations for pancreatitis. Fifteen of the 16 patients with biliary tract disease and all patients with congenital anomalies required operation. Six of the 16 patients with trauma required operation and none of those with systemic disease. As in adults ultrasonographic examination and CT scan are most important in the diagnosis; medical treatment consists of intravenous (I.V.) fluids, nasogastric suction, and total parenteral nutrition (TPN), and risk factors can help predict the severity of the disease while amylase alone is not related to severity. Different from adults, in children an etiology can usually be determined. The common etiologies, biliary tract disease, trauma, and congenital anomalies frequently require operation. PMID- 3345114 TI - Surgical oncology research. A disappointing status report. AB - The purpose of this paper is to evaluate certain aspects of the present status of surgical oncology research. We have attempted to define the magnitude of the problem, characterize features unique to the surgical community, and formulate potential solutions. Demographic data concerning grant applications submitted to and funded by the National Cancer Institute (NCI) over the time period from 1980 to 1985 were analyzed. Departments of surgery submitted and were awarded substantially fewer grants over the study period than departments of medicine. Additionally, the number of applications submitted from departments of medicine increased during this time period while those from departments of surgery declined. This record is particularly worrisome because it occurred during a period of time of unprecedented scientific and educational opportunities and support mechanisms provided by the NCI. Further conclusions and potential solutions are discussed in this paper. PMID- 3345115 TI - Weight loss with physiologic impairment. A basic indicator of surgical risk. AB - It is a long held belief that weight loss is a basic indicator of surgical risk. Many experienced surgeons, however, think otherwise. We have investigated the proposition that weight loss is a risk factor for postoperative complications but only when associated with clinically obvious physiologic impairment. Before major surgery, 102 patients had a careful history taken to ascertain if there had been recent weight loss and a reduction in the capacity for activity. Physical examination included assessment of mood, skeletal muscle function, respiratory muscle function, and wound healing. Plasma albumin was also measured. Using this information the patients were placed into one of three groups. Group I (N = 43) were normal, group II (N = 17) had weight loss greater than 10% but no clinical evidence of physiologic impairment, and group III (N = 42) had weight loss greater than 10% with clear evidence of dysfunction of two or more organ systems. The patients in group III had significantly more postoperative complications (p less than 0.05). They also had more septic complications (p less than 0.02) including a higher incidence of pneumonia (p less than 0.05) and a longer hospital stay (p less than 0.05) than patients in each of the other two groups. Objective measurements of body stores of protein and liver, and psychologic, respiratory, and skeletal muscle function, confirmed the validity of the clinical classification into the risk groups. The results demonstrate that weight loss is a basic indicator of surgical risk in modern practice providing it is associated with clinically obvious impairment of organ function. They suggest that adequate body protein stores are necessary for normal body function and for minimizing the risks of surgery. PMID- 3345116 TI - Reoperations for persistent and recurrent secondary hyperparathyroidism. AB - Forty-nine reoperations for persistent or recurrent secondary hyperparathyroidism (HPT) in 30 patients are reported. The patients are part of a total of 184 patients operated on for secondary HPT; 28 reoperations in 18 patients were performed in the neck or in the upper mediastinum for remaining glands. Eleven reoperations at the forearm autograft revealed hyperplasia of the grafted tissue as the reason for recurrent disease in seven patients; they were treated by excision of all grossly enlarged particles. Ten patients received autologous cryopreserved tissue because of permanent postoperative hypoparathyroidism. The rate of graft-dependent recurrent HPT was 7%, and inadequate graft function was found in 6% of the patients. PMID- 3345117 TI - The improving long-term outlook for patients over 70 years of age with abdominal aortic aneurysms. AB - During the past decade, selective criteria for elective surgery for abdominal aortic aneurysms have been refined based on natural history and aneurysm expansion information. Using these criteria, contemporary preoperative preparation and newer intraoperative technical adjuncts, 123 consecutive patients underwent elective resection with 1 death (mortality rate: 0.8%). These include all patients operated on with both elective and urgent aneurysms at this institution since 1978, with the exception of those with frank rupture. Most importantly, however, the 5-year life-table survival of all of these patients (average age: 71.3 years, range 46-96 yr) was 72%, including both hospital and late mortality rates. More than half of the patients were over 70 years old (78 cases), with no hospital deaths and a 5-year life-table survival probability of 67%. For those under 70 years of age at the time of operation, the 5-year life table probability of survival was 79%. We believe that these accomplishments were a direct result of an aggressive policy of screening for and selectively treating coronary disease and carotid stenosis preoperatively and the utilization of such intraoperative adjuncts as routine Swan-Ganz monitoring, autologous blood transfusion, the cell saver, and the frequent use of the tube grafting (50%). Thus, with proper selection, the outlook for the patient over 70 years old with an elective abdominal aortic aneurysm resection now approaches that of the normal population (67% vs. 69%). PMID- 3345118 TI - The acute surgical abdomen after cardiac surgery involving extracorporeal circulation. AB - From 1972 through 1984, 7140 cardiac operations were performed at one university teaching hospital; they were reviewed to elucidate common factors in patients developing an acute surgical abdomen after cardiac surgery and extracorporeal circulation. Twenty-one patients (0.29%) developed an acute surgical abdomen in the period following cardiac surgery. The abdominal surgical complications were, in general, due to complications of peptic ulcer disease, decreased intestinal blood flow, and cholecystitis. There was no correlation between preoperative history, physical examination, cardiac function, laboratory data, and the subsequent development of an acute abdomen. Mortality rate, 24% after abdominal surgery, was increased with emergency cardiac operations, combined cardiac procedures, complications of cardiac surgery, unnecessary delay of abdominal surgery, and abdominal wound complications. Major abdominal wound complications were seen in 38%. Patients undergoing cardiac surgery may develop a variety of common abdominal surgical disorders. Patients so inclined cannot be identified prior to cardiac surgery. Ulcer prophylaxis, wound management, prompt resuscitation, and timely surgery are critical. PMID- 3345119 TI - Management of stab wounds to the thoracoabdominal region. A clinical approach. AB - We studied 324 patients admitted to Harlem Hospital Center from July 1981 to June 1986 with stab wounds of the thoracoabdominal region (area limited by a coronal circle through the fifth interspaces anteriorly and seventh interspaces posteriorly from above to a subcostal circle 5 cm caudad to the costal margins and 12th ribs from below). We divided this region into 12 zones (six symmetrical zones on each side) using the above upper and lower limits and the costal margins, the midlines, and the anterior and posterior axillary lines. This study was conducted to determine the incidence of transdiaphragmatic penetration for the thoracoabdominal region stab wounds in each of the 12 zones identified for the first time and applied in this study, and the reliability and safety of surgical management based mainly on physical examination. The highest incidence of transdiaphragmatic penetration occurred in stab wounds of the left anterior lower thoracic zone (21.7%). The lowest incidence was 0% and the overall incidence was 11%. Physical examination was accurate in making the diagnosis in 95.4% of all cases and no mortality was associated with a delay in diagnosis that may have resulted from the serial physical examinations. We conclude that this method of selective operative management based on physical examinations is accurate and safe. PMID- 3345120 TI - Microbial colonization of tumors in relation to the upper gastrointestinal tract in patients with gastric carcinoma. AB - The microbial colonization of the oropharynx, the esophagus, the stomach, and the duodenum was studied in relation to the microbial flora found on tumor and gastric mucosal biopsies in 23 patients with gastric carcinoma. The tumor was colonized in all patients, and the stomach, the esophagus, the duodenum, and the gastric mucosa were colonized in 96%, 87%, 83%, and 78% of the patients, respectively. The most common microorganisms isolated were streptococci, bifidobacteria, lactobacilli, and Bacteroides species, belonging to the normal oropharyngeal flora. Microbial colonization with gram-negative rods, Clostridium species or yeasts, was present in at least one site in 91% of the patients. Clostridium species were isolated from 57% of the patients. The total numbers of microorganisms recovered from the tumor biopsies did not vary with the intraluminal gastric pH. A relation between the gastric pH and the total number of microorganisms in the gastric juice existed. Significant higher numbers of different strains of microorganisms (p less than 0.005) colonized the tumor compared to the gastric mucosa. Anaerobic microorganisms colonized the tumor significantly more often than the mucosa (p less than 0.001). Antibiotic agents used as prophylaxis in gastric cancer surgery should cover both aerobic and anaerobic microorganisms, including B. fragilis. PMID- 3345122 TI - So duplicate chemistry profiles correlate with multiple physicians. Let's not blame the doctors! PMID- 3345121 TI - Results of salvage surgery for mammary recurrence following breast-conserving therapy. AB - A retrospective analysis was performed of 118 surgically treated mammary recurrences, occurring following primary conservative excision and radiation therapy for clinical Stages I and II breast cancer. Actuarial cancer-specific survival following salvage surgery was 72% at 5 years and 58% at 10 years. With a median followup of 7 years, further local-regional recurrences were observed in 20 of the 118 patients, many of whom could be treated by further surgery. Actuarial survival after recurrence was significantly influenced by initial clinical stage, as well as by the disease-free interval following primary therapy, but was similar for both premenopausal and postmenopausal patients and for patients treated by radical or breast-conserving salvage operations. For recurrences after the fifth year, actuarial survival following salvage surgery was 83% and 68% at 5 and 10 years, respectively. Survival for Stage I patients was favorable regardless of disease-free interval. It is concluded that recurrences in the breast following primary treatment with limited surgery and irradiation have a considerably more favorable prognosis than that of local failures after primary radical surgery. Suggestions for the management of these recurrences are presented. PMID- 3345123 TI - Test-ordering by multiple physicians increases unnecessary laboratory examinations. AB - In modern teaching hospitals, patients typically receive direct care from a succession of different physicians, each of whom may order diagnostic tests on the same patient. We examined the association of test-ordering by multiple physicians with unnecessary duplication of 20-test chemistry profiles in 198 consecutively admitted patients. In a multivariate regression model, the number of duplicate chemistry profiles ordered for a patient was significantly correlated with the number of physicians ordering profiles after controlling for the overall intensity of profile testing. In a case-control analysis comparing duplicate with nonduplicate profiles, redundant tests were significantly more likely to have been ordered by a new physician who had not ordered a patient's previous profile than by the same physician who had ordered the previous chemistry panel. We conclude that test ordering by multiple physicians, the prevalent pattern in almost all teaching hospitals, predisposes to unnecessary laboratory examinations. PMID- 3345124 TI - A physician office analyzer. Evaluation of quality of results obtained by technical and nontechnical personnel. AB - We evaluated the Abbott Vision analyzer (Abbott Laboratories, North Chicago, Ill) both in a controlled laboratory setting and with several untrained individuals. We used control serum samples supplied by the manufacturer. Method comparison was performed with methods currently in use in our laboratory. The analytes evaluated were glucose, urea nitrogen, urate, cholesterol, triglycerides, and alkaline phosphatase. In the laboratory, the within-run precision (coefficient of variation) of all methods ranged from 0.8% to 3.4%; the range for between-run precision was 1.2% to 3.3%. Correlation between the Abbott Vision analyzer and routine methods was excellent. The upper limit of linearity for all methods was as stated by the manufacturer. The coefficient of variation obtained by ten nontechnical personnel ranged from 0.0% to 3.9%. The correlation between results obtained by the nontechnologist were excellent. Our study indicates the Abbott Vision analyzer is extremely easy to operate and provides reliable results in the hands of nontechnical personnel. PMID- 3345125 TI - Xanthogranulomatous pyelonephritis. A reappraisal and immunohistochemical study. AB - The clinicopathologic features of 17 patients with xanthogranulomatous pyelonephritis are described, together with results on a number of histochemical and immunohistochemical techniques that were used to demonstrate the variety of cells involved. Based on our clinicopathologic data and review of the literature, we believe that xanthogranulomatous pyelonephritis should be regarded as a destructive, and, at times, tumefactive inflammatory process that may complicate chronic pyelonephritis. The initiation of this process remains an enigma. However, there appears to be three main features that are associated with xanthogranulomatous pyelonephritis: pelvicalyceal obstruction, ulceration of the pelvicalyceal urothelium, and bacterial infection. PMID- 3345126 TI - Histopathologic features of liver biopsy specimens in sickle cell disease. AB - Liver biopsy results and clinical records from 13 patients with sickle cell anemia were reviewed to assess the relative importance of local ischemia or of factors unrelated to sickling as a cause of their liver disease. Two of the biopsy specimens were normal and one showed cirrhosis. Nine patients had received multiple blood transfusions and nine had cholelithiasis, of whom two also had choledocholithiasis. Seven had both risk factors. Five had lobular cholestasis and four had acute or chronic hepatitis. One biopsy specimen showed changes of the Budd-Chiari syndrome. Another showed clear portal tract changes of large bile duct obstruction but no mechanical blockage of the biliary system; this suggests the thickened bile as postulated by Muirhead. Otherwise the changes observed were those to be expected in a heavily transfused population with a high prevalence of gallstones. PMID- 3345128 TI - Sinus histiocytosis with massive lymphadenopathy. Occurrence in identical twins with retroperitoneal disease. AB - Sinus histiocytosis with massive lymphadenopathy (SHML) was originally defined as a relatively specific benign pseudolymphomatous disorder. Although the etiology remains unknown, the spectrum of SHML has been expanded to include predominance of extranodal disease in some patients, clinically significant immunologic abnormalities in 10% of patients, and fatal outcome in 7% of patients. We report the rare occurrence of SHML in identical twins; to our knowledge, SHML in identical twins has been reported only once previously. The two patients described are also unusual because of the predominance of retroperitoneal disease with minimal peripheral adenopathy. After a seven-year clinical course, one twin died of extensive retroperitoneal disease, liver failure, bleeding diathesis, and seizure disorder. The other twin is alive after a six-year course of progressive retroperitoneal disease. PMID- 3345127 TI - Use of Nile red stain in the detection of cholesteryl ester accumulation in acid lipase-deficient fibroblasts. AB - The fluorescent hydrophobic probe Nile red was used to distinguish between normal human fibroblasts and fibroblasts from individuals with a genetic deficiency in lysosomal acid lipase activity (Wolman's disease and cholesteryl ester storage disease). The fluorescence of Nile red-stained cultured mutant cells, indicative of neutral lipid accumulation, was intense when compared microscopically with normal fibroblasts. The cholesteryl ester accumulation in the acid lipase deficient fibroblasts was demonstrated qualitatively and quantitatively when cellular lipid extracts were subjected to thin-layer chromatography, followed by Nile red plate treatment and fluorescence spectrometry scanning. These results demonstrate the utility of the Nile red stain to document cellular lipid overloading. The techniques are simple to perform and can effectively supplement the standard enzymatic analysis used in the diagnosis of acid lipase deficiency. PMID- 3345129 TI - Ectopic parathyroid tissue within the vagus nerve. Incidence and possible clinical significance. AB - A postmortem study of 64 vagus nerves from 32 children up to 1 year of age was done to determine the incidence of ectopic parathyroid tissue. The segments of nerve (average length, 2.6 cm), including the entire ganglion nodosum, were examined using a combination of step and serial sectioning. Discrete solitary collections of ectopic parathyroid chief cells were seen in 6% of vagus nerves and ranged in diameter from 162 to 360 micron. Confirmation of the nature of the cells was based on the presence of abundant glycogen and positive immunoreactivity for chromogranin and parathormone. The possible significance of intravagal parathyroid tissue is briefly discussed. PMID- 3345130 TI - The distribution of extracellular matrix vesicles in healing of rat tibial bone three days after intramedullary injury. AB - The distribution of extracellular matrix vesicles on the third day of bone healing was studied by morphometric analysis of transmission electron micrographs. Detection and grouping of the vesicles was performed according to type, diameter, and distance from the calcified front. The different types were selected as follows: vesicles with electron-lucent contents ("empty"), vesicles with amorphous electron-opaque contents ("amorphic"), vesicles containing crystalline depositions ("crystal"), and vesicles containing crystalline structures with ruptured membranes ("rupture"). The majority of vesicles were between 0.07 micron and 0.12 micron in diameter and were located at less than 3 micron from the calcified front. The distribution of the "empty", "amorphic", "crystal", and "rupture" vesicles was 23.2%, 74%, 2.5%, and 0.3% respectively. Their sequence of arrangement according to diameter was as follows: "empty", "amorphic", "crystal", and "rupture", the empty vesicles constituting the smallest and the "rupture" the largest type. Distances from the calcified front were similar for the "empty", "amorphic", and "crystal" vesicles, while the "rupture" type was located nearest to the front. The present observations support the widely acknowledged hypothesis on the role of extracellular matrix vesicles in mineralization. It is thought that the secretion of "empty" vesicles from the cell is followed by intravascular accumulation of amorphous Ca and Pi to form a hydroxyapatite crystal that, in turn, ruptures the vesicle's membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345131 TI - Measurement of bending and torsion with and without an intramedullary nail implanted in sheep tibia in vivo. AB - This report concerns the analysis of the dynamic measurements of torque and bending on nailed tibiae, using two sheep walking at different speeds on a treadmill, both before and after nailing. The amplitude and the period of the measured values are reported and discussed in relationship to the speed and duration of the experiment. PMID- 3345133 TI - Eighteen-year anamnesis of osteoid osteoma--a diagnostic problem? AB - The 18-year history of osteoid osteoma in a woman aged 43 is presented. The typical physical and radiographic findings are described. Total removal of the tumor resulted in prompt and permanent relief of symptoms. Diagnosis, histopathology, differential diagnosis, treatment, and prognosis of the tumor are discussed. PMID- 3345132 TI - The role of macrophages and giant cells in loosening of joint replacement. AB - Macrophages and foreign-body giant cells from the bone-cement interface of loosened joint replacement were assayed for direct bone resorption in an in vitro experimental model. Human osteoclasts from giant cell tumors and experimental animal osteoclasts were not capable of resorbing the bone under experimental conditions, but osteoclasts are. It is suggested that macrophages and giant cells in loosened implants may initiate bone resorption, removing the extra-cellular barrier that normally protects mineral crystals from osteoclastic recognition. PMID- 3345134 TI - Acetabuloplasty for congenital dislocation of the hip in children. AB - A modified acetabuloplasty, which has been employed at our hospital since 1977, is described for the treatment of congenital dislocation of the hip in children. The procedure has been performed on a total of 74 hips in 61 children (average age 6.7 years), with satisfactory results obtained in 87.8% of hips. The technique, its indications, and pre- and postoperative management are detailed. The procedure possesses the advantages of both the shelf and Pemberton procedures and has proved to be an effective operation for older children with poor acetabular development. Our results show that, when performed correctly, this procedure is simple, safe, and effective. PMID- 3345135 TI - Vascularized pedicled pubic graft. A topographical anatomical study in human cadavers. AB - The topographical anatomy and the vascular variety of the pubic arch was studied on ten fresh human cadavers (15 hemipelves). The idea was to obtain a pedicled vascularized bone graft to be used in the hip region and as an alternative to an iliac crest pedicled graft. The size of the possible graft and the length of the pedicle were measured and evaluated. PMID- 3345137 TI - Congenital contracture of the infraspinous muscle. A case report. AB - Posterior subluxation of the glenohumeral joint and a posterior, winged scapular deformity have been reported in a patient with congenital contracture of the infraspinous muscle. The present case was successfully treated by resection of the contracted band within the infraspinous muscle, glenoid osteotomy, reverse Putti-Platt, and resection of the protruding part of the scapula. To our knowledge, this is the first case reported of congenital contracture of the infraspinous muscle. The pathogenesis of the deformity in this case is discussed. PMID- 3345136 TI - Improved cementation in total hip replacement. AB - Insufficient cementation has been suggested to be the most common cause of loosening of the femoral component after total hip arthroplasty. A clinical and radiographic study of 129 consecutive, primary total hip replacements was performed 5 years after surgery, in order to evaluate the significance of femoral plugging, special attention being focused on cementation and radiographic loosening. A polyethylene medullary plug was used in 78 hips which were compared with 51 non-plugged hips with respect to the clinical course and radiographic appearance. The cement mantle around the femoral component was thicker, and the packing of cement significantly improved when the plug was used. The frequency of radiographic loosening was smaller in the plugged group but with no statistical significance. There was no difference in clinical results between the compared groups. Our results indicate that medullary plugging improves the cementation and in particular prevents insufficient cementation of the femoral component. PMID- 3345138 TI - Rotator cuff tear--relationship between clinical and anatomopathological findings. AB - Rotator cuff tears (RCT) are frequent and increase with age. Why do only a relatively small percentage cause a permanent severe handicap justifying surgery? Is there a relationship between size and site of the tear and the clinical symptoms? How do they influence the postoperative result? These questions were answered in a prospective study of 76 operated patients. We adopted D. Patte's classification of the RCT into four groups according to the site and size of the lesion. Our figures were compared with those obtained by Patte in an analogous study of 256 cases. Of the tears in our series, 56.5% belonged to groups I and II, which means that only the supraspinatous and occasionally also the subscapular muscles were involved. In 100% of the cases in group I we found only pain, whereas a pure symptomatology with pain alone was presented in only 51% of group II, in 48% of group III, and in 0% of group IV. Groups III (35.5%) and IV (8%) represent more extensive tears, involving not only the anterior part of the rotator cuff, e.g., the supraspinatous tendon, but also to a more or less severe extent, the infraspinatous and sometimes even the teres minor. In group IV the extensive tear is combined with osteoarthritic changes. In both groups a mixed symptomatology (pain and pseudoparalysis) is the rule. The result of operative treatment is satisfactory in all groups as far as pain relief is concerned. The improvement of active ROM is not as evident and seems, as expected, to be related to the severity of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345139 TI - Preschool vision screening starts at 6 months of age. PMID- 3345140 TI - Effects of topical ALO 2145 (p-aminoclonidine hydrochloride, aplonidine hydrochloride) on the acute intraocular pressure rise after argon laser iridotomy. PMID- 3345141 TI - Erythrocyte sedimentation rate and its relationship to hematocrit giant cell arteritis. PMID- 3345142 TI - A multiple lens carrying case. PMID- 3345143 TI - Modified disposable endoilluminator. PMID- 3345144 TI - Toxicity of flurbiprofen sodium. Case report. PMID- 3345145 TI - AIDS presenting as acute glaucoma. Case report. PMID- 3345146 TI - Giant cell reaction in pterygium. Case report. PMID- 3345147 TI - Silicone oil for proliferative vitreoretinopathy. Does it help or hinder? PMID- 3345148 TI - Evaluation of a Lens Opacities Classification System. AB - A simple system, based on standard photographs, has been developed to classify lens opacities. The system allows the definition of cataract cases and noncases according to the location of lens opacification (nuclear, cortical, posterior subcapsular) and its extent (early or more advanced). Evaluation of the system has shown good to excellent reproducibility for clinical and photographic classifications. Comparisons of clinical and photograph-derived gradings has shown generally good agreement in classifying the presence and type of cataract; this agreement is highest for nuclear cataract. Photographic gradings of posterior subcapsular and, to a lesser degree, cortical opacities tend to underestimate the extent of opacification found by clinical gradings. The Lens Opacities Case-Control Study system is simple, reproducible, and easy to implement; it is offered for use in case-control and other cross-sectional studies of cataract with compatible classification goals. PMID- 3345149 TI - Lens Opacities Classification System. AB - The Lens Opacities Classification System (LOCS) is a simple system for classifying age-related human lens opacities at the slit lamp or in retroilluminated and slit-lamp photographs. The system employs a set of standard Neitz CTR retroilluminated black-and-white photographs for classification of cortical and posterior subcapsular cataracts and a single color slit-lamp photograph for classification of nuclear color and opalescence. We present a detailed description of the system. PMID- 3345150 TI - Exfoliation syndrome. Prevalence in a southeastern United States population. AB - A prospective study of 2121 patients in the southeastern United States having no evidence of glaucoma, suspected of having primary open angle glaucoma, having primary open angle glaucoma, or having open angle glaucoma with exfoliation syndrome revealed an overall prevalence of exfoliation syndrome of 1.6% and a prevalence in the glaucoma subpopulation of 6.0%. All but one of the 33 patients with exfoliation syndrome were at least 60 years of age, and the prevalence of exfoliation syndrome in the subgroup of 1000 patients in this age group was 3.2%. Among the patients in this age group who did not have open angle glaucoma, 1.6% had exfoliation syndrome, and this prevalence was significantly less than those reported in studies from other geographic areas. PMID- 3345151 TI - Antioxidant status in persons with and without senile cataract. AB - The relationship between biochemical markers of antioxidant status and senile cataract was examined in 112 subjects aged 40 to 70 years. Seventy-seven of these subjects had a cataract in at least one lens. Antioxidant status was measured using erythrocyte superoxide dismutase, glutathione peroxidase, and glucose-6 phosphate dehydrogenase activity, and indexes that included these enzymes plus plasma levels of vitamin E, vitamin C, and carotenoids. Subjects were grouped by level (low, moderate, or high) of the enzymes and antioxidant indexes. Results suggest that subjects with high levels of at least two of the three vitamins (vitamin E, vitamin C, or carotenoids) are at reduced risk of cataract relative to subjects with low levels of one or more of these vitamins (odds ratio, 0.2). The erythrocyte enzymes, either individually or in combination, did not appear to differ between subjects with and without cataract. PMID- 3345152 TI - Reliability of brightness comparison testing in predicting afferent pupillary defects. AB - We tested the reliability of brightness comparison testing in predicting relative afferent pupillary defects (RAPDs) in 206 patients. For unselected patients, brightness comparison testing correctly predicted the RAPD in 62% of patients. For subgroups of patients with glaucoma and optic nerve lesions, correct predictions were made in 92% and 83% of patients, respectively. Sensitivity and specificity of brightness comparison testing with a 6-V test light were 85% and 49%, respectively. In subgroups of patients who are strongly suspected of having an RAPD but in whom pupillary testing is not possible, brightness comparison testing can reliably predict presence or absence of an RAPD. PMID- 3345153 TI - Quantitative assessment of postsurgical breakdown of the blood-aqueous barrier following administration of 0.5% ketorolac tromethamine solution. A double masked, paired comparison with vehicle-placebo solution study. AB - Preoperative and serial postoperative anterior chamber fluorophotometry were performed after oral administration of fluorescein sodium in patients undergoing extracapsular cataract extraction and posterior chamber intraocular lens insertion. The administration of topical 0.5% ketorolac tromethamine solution before and after surgery markedly decreased the breakdown of the blood-aqueous barrier compared with vehicle-placebo solution administration at each time period, as measured by fluorophotometry. Corticosteroids were not given to any patients throughout the duration of the study. These fluorophotometric results correlated well with slit-lamp observations of postoperative ocular inflammation. Both ketorolac and vehicle were well tolerated by patients. No effects on intraocular pressure were seen with ketorolac administration. This study suggests that ketorolac ophthalmic solution is effective and safe as a nonsteroidal anti inflammatory agent for topical use following cataract surgery and intraocular lens implantation. PMID- 3345154 TI - Abnormal axonemes in X-linked retinitis pigmentosa. AB - Sperm of patients with X-linked retinitis pigmentosa (RP) was studied to assess the state of the axoneme in this genetic subtype. Semen samples were collected from eight patients with X-linked RP and compared with a database of 31 controls. Semen was also collected from two patients with other retinal degenerations (choroideremia and fundus flavimaculatus) and patients with simplex RP. All controls and patients were studied under a masked protocol. There was a significant increase in the percentage of abnormal sperm tails at both the light and electron microscopic levels in patients with X-linked RP only. Thus, X-linked RP is associated with an alteration in sperm axoneme structure. Sperm cell analysis may serve as a useful model system for additional investigations into the pathogenesis of this disease. PMID- 3345156 TI - Aqueous humor penetration of ciprofloxacin in the human eye. AB - Two doses of ciprofloxacin were administered intravenously, 200 mg every 12 hours, to 25 patients undergoing cataract surgery. Plasma and aqueous humor were obtained at 1, 3, 5, 7, and 9 hours after the administration of the second dose of the drug. Peak intraocular concentrations (mean +/- SD), 0.21 +/- 0.1 mg/L, were detected at one hour following ciprofloxacin administration. A time dependent decrease of the penetration was observed, and by nine hours after the administration, ciprofloxacin levels were 0.05 mg/L. These results illustrate that ciprofloxacin may be an effective antimicrobial agent for prophylactic use in ophthalmologic surgery and also for the treatment of intraocular infections due to susceptible organisms. PMID- 3345155 TI - Acute radiation injury of ocular adnexa. AB - Eyelids and lacrimal glands of monkeys examined histologically 24 and 48 hours after receiving 2.5 to 20.0 Gy (250 to 2000 rad) of cobalt 60 radiation contained acute inflammation. Cells of meibomian glands, other sebaceous glands, sweat glands, and goblet cells displayed no significant alterations. Acinar cells of major and accessory lacrimal glands and, to a lesser degree, lacrimal duct epithelium showed degeneration and necrosis that were increased in extent in proportion to the radiation dose. Reduced numbers of serous acini and decreased size of remaining acini indicate that atrophy of lacrimal glands can be recognized within two days after irradiation. The morphologic diagnosis for irradiated lacrimal glands was acute, necrotizing dacryoadenitis. PMID- 3345157 TI - Cellular proliferation induced by subretinal injection of vitreous in the rabbit. AB - A new experimental model of subretinal cellular proliferation, based on injection of autologous vitreous into the subretinal space of rabbits, was studied by light and electron microscopy. As early as five days after injection, proliferation of retinal pigment epithelial (RPE) and retinal glial cells was observed in the subretinal space. These morphologically distinct proliferating cells were sometimes joined by junctional complexes. Morphologically, the proliferating RPE cells resembled either RPE cells or fibroblasts. Some proliferating RPE cells also retained their epithelial characteristics (ie, basement membranes and cell junctions), while others were partially dedifferentiated and showed some embryonic features. New formation of melanin could be identified within the proliferated RPE cells, which could account, in part, for the hyperpigmentation at the site of the bleb caused by the injection of vitreous. The results demonstrated that injection of autologous vitreous into the subretinal space can lead to subretinal proliferation of retinal glial and RPE cells in the rabbit. PMID- 3345158 TI - A new device for performing fluid-gas exchanges. AB - A new device was developed for performing outpatient fluid-gas exchanges in vitrectomized eyes. This device allows the operator to hold his needle in position steadily with less effort and fatigue. It is particularly useful for fluid-gas exchanges in phakic eyes where precise needle positioning is required. PMID- 3345159 TI - Compulsory vaccination. PMID- 3345160 TI - Learning to cope with grief. PMID- 3345161 TI - Medical allsorts. PMID- 3345162 TI - Stress in general practice. PMID- 3345164 TI - The demanding patient. PMID- 3345163 TI - Stress management and the general practitioner. PMID- 3345165 TI - Child abuse and the role of the GP. PMID- 3345166 TI - Malpractice suits. Minimising the risks. PMID- 3345167 TI - Parkinson's disease. PMID- 3345168 TI - Injection and 'no' injection tips. PMID- 3345169 TI - Physician, heal thyself. PMID- 3345170 TI - Acceleration-induced electrocardiographic interval changes. AB - The electrocardiographic intervals (PR, QRS, QT, and RR) before, during, and post +Gz stress were measured in 24 healthy male subjects undergoing +Gz centrifuge exposure. The PR and QRS intervals responded in a predictable manner, shortening during stress and returning to baseline resting values post-stress. The QT interval, however, was not observed to be dependent solely on heart rate. Bazett's formula, which was developed to correct for heart rate variability, did not adequately result in a homogeneous correction of the QT interval for each stress-related period. During +Gz stress, the QT was shortened, and the QTc prolonged. The QT interval remained shortened even though the heart rate returned to baseline (with the QTc undercorrected) in the post-stress period. The QT (QTc) interval variations probably reflect the effects of both heart rate and autonomic balance during and after +Gz stress, and may provide a measure of the prevailing autonomic (sympathetic or parasympathetic) tone existing at a given point associated with +Gz stress. These electrocardiographic interval changes define the normal response for healthy individuals. Individuals with exaggerated autonomic responses could be identified by comparing their responses to these normal responses resulting from +Gz stress. PMID- 3345171 TI - Cardiovascular responses to head-up tilt after an endurance exercise program. AB - The cardiovascular responses to 10 min of orthostasis were assessed before and after an aerobic exercise program. Five men and five women (18-25 years old) exercised for 7 weeks, four times per week, for 50 min per session at 70% of maximal heart rate (HR). Before and after the exercise program, maximal aerobic power (VO2max) was determined, and HR, systolic (SBP), diastolic (DBP), and pulse (PP) blood pressures were measured each minute during 5 min of supine rest, 10 min of foot-supported 70 degree head-up tilt (HUT), and 5 min of supine rest. Orthostatic tolerance was not determined. Calf compliance was measured in five of the subjects before and after the program as the change in leg volume at occluding pressures of 20, 40, 60, 80, and 100 mm Hg. Following the program, VO2max increased by 8.7% (p = 0.012), while decreases were noted in resting HR (9.4%, p = 0.041), SBP (5.0%, p less than 0.0005), and DBP (14.2%, p less than 0.0005). Despite a greater HR increase during HUT (7.1 beat.min-1, p = 0.034), SBP decreased by 3.4 mm Hg during HUT after the exercise program (p = 0.008). No differences were noted in the changes in DBP, MAP, or PP upon tilting (p greater than 0.05). After the program, the amount of fluid pooled in the calf at high occluding pressures (80 and 100 mm Hg) increased by 0.96 +/- 0.24 and 1.10 +/- 0.33 ml.100 ml tissue-1 (X +/- S.E.M., p = 0.017 and p = 0.028, respectively). We suggest that control of blood pressure during 10 min of orthostasis may be altered by endurance exercise training. PMID- 3345172 TI - Performance-based assessment of oculomotor efficiency. AB - Acquisition of visual information from spatial points disparate enough to necessitate head and eye movement involves the vestibular and other oculomotor control systems in shifting and stabilizing gaze relative to those points. In the present study, a simple procedure to test oculomotor abilities was developed and evaluated; it uses performance (serial letter identification) to maintain initial gaze position and performance (number of digits correctly identified) to measure the efficiency of gaze-shift control. Number of digits acquired from briefly displayed digit sets was consistently and powerfully influenced by exposure duration of digit sets and to a lesser extent by the size of required gaze shift. The performance of normal subjects in eye movement and head-and-eye movement conditions is predictable from static performance of normals. Results suggest that the procedure will be sensitive to certain types of central nervous system and vestibular pathology. Substantial individual differences in performance dependent upon gaze-shift control were found among normal subjects. If some pilots operate at the lower extremes of the performance distribution, they may be subject to critical response deficiencies in emergency conditions requiring large gaze shifts. PMID- 3345173 TI - A comparison of the dynamics of horizontal and vertical smooth pursuit in normal human subjects. AB - We compared horizontal and vertical smooth pursuit recorded with a scleral contact lens technique at multiple sinusoidal frequencies (0.2-1.6 Hz) and peak velocities (12.5-100 degrees.s-1) in 10 normal subjects. The gain was significantly higher (p less than 0.05) and the harmonic distortion significantly lower (p less than 0.05) for horizontal pursuit compared to vertical pursuit for all stimuli except the lowest frequency and peak velocity. Both horizontal and vertical pursuit exhibited a phase lag that was minimal at lower frequencies but reached a mean of about 37 degrees at 1.6 Hz. This difference between horizontal and vertical pursuit could be explained by current models of the smooth pursuit system if one postulates a lower saturation level of retinal error velocity for vertical pursuit compared to horizontal pursuit. PMID- 3345174 TI - Chromatic aftereffects associated with a night vision goggle simulation. AB - A visual perception experiment was conducted to determine the chromatic aftereffects of viewing a yellow-green field that simulated the display of current night vision goggles. Six females and two males served as subjects in a color-naming procedure. Subjects sequentially viewed an adaptation field, which was either yellow-green or white, and small colored targets presented on a CRT display. The time required to name the color of the targets was found to be dependent on the color of the adaptation field, the color of the target, and the interaction of these two variables. It was recommended that the effects of attenuation of the luminance of the night vision goggles be studied, and that color cockpit displays be redundantly coded whenever possible. PMID- 3345175 TI - Dark focus measured in Navy jet tactical fighter pilots. AB - Visual accommodation was measured with the laser-Badal optometer in 98 U.S. Navy fighter pilots who were in a dark environment without visual stimuli. The average dark focus of the pilots was 0.25 diopters of myopia; 40% were either emmetropic or hyperopic in the dark. Only 4% had as much dark myopia as 50% of a sample of 220 college students. Although the jet fighter pilots, as a population, differed from college students in terms of dark focus, it remains to be determined whether the remarkable dark focus of the pilots was a function of training or selection. The dark focus measurements of the pilots were compared to their mean night carrier landing scores and their mean target detection slant range scores--the distance at which an adversary aircraft is first sighted during an air combat maneuver training engagement. Neither the night carrier landing scores nor the target detection slant range scores correlated significantly with dark focus measurements. PMID- 3345176 TI - Effect of long-term physical exercise on lymphocyte reactivity: similarity to spaceflight reactions. AB - The response of critical immunological parameters in seven athletes to the sustained physical stress of marathon running was assessed. Variables analysed were the responsiveness of lymphocytes (measured as mitogenic response to concanavalin A), the numbers of lymphocytes, their subsets, and leukocyte numbers. In addition, blood levels of cortisol, epinephrine, and norepinephrine were determined. After the run, lymphocyte responsiveness was severely depressed to 1-70% of the resting values, even though the lymphocyte counts did not change. Leukocyte counts were elevated 2.8-fold. No dramatic changes were found within the lymphocyte subsets, although an increase in pan T-cells and the helper/inducer subset 2 d after the run was significant. In addition, the numbers of B-cells decreased significantly. No change was observed within the suppressor/cytotoxic subset. Cortisol increased 2.1-fold, epinephrine 3.2-fold and norepinephrine 2.7-fold. All these parameters returned to baseline values within 2 d. These data were compared with data obtained during and after spaceflight. We conclude that prolonged physical stress of marathon running induces changes in immunological responsiveness that are strikingly similar to those arising from the stress of spaceflight. PMID- 3345177 TI - Operation Everest II: lack of an effect of extreme altitude on visual contrast sensitivity. AB - Contrast sensitivity thresholds were studied over 40 d during gradual ascent to a simulated terrestrial altitude of 25,000 ft in a decompression chamber. Only ambient pressure, and thus inspired oxygen pressure, was varied, thereby eliminating many of the confounding effects of cold, dehydration, malnutrition and exhaustion, inevitably encountered on very high mountains. Contrast sensitivity thresholds measured by the Ginsburg Vistech test showed no overall impairment as altitude increased. These results are different from those of other previously reported vision studies involving shorter exposures, lower altitudes, and lower test luminances. However, our results can be explained on the basis of the higher stimulus luminances used in our contrast sensitivity testing. Compared to the luminance levels involved in previously reported testing, our higher luminance stimuli would be less likely to be affected by hypoxia. PMID- 3345178 TI - Aircrew selection: a prospective study. AB - The medical reasons for rejection among 3,000 consecutive applicants for flight training were evaluated, and the effectiveness of the screening process determined by reviewing subsequent medical wastage occurring during flight training. Of the 46 cadets who left the course because of medical reasons, 8 withheld information which would have led to their rejection on the original screening examination (epilepsy 1, recurrent syncope 1, migraine headache 2, Crohn's disease 1, asthma 1, chronic knee pain 1, and chronic recurrent headaches 1). There were also two errors in medical processing. The other 36 cases could not have been predicted by current screening procedures. We conclude that the major deficiency in our screening process is the concealment or withholding of information by candidates for flight training. PMID- 3345179 TI - Health profile of U.S. Navy pilots of electronically modified aircraft. AB - This study compared hospitalization rates of pilots who primarily flew electronically modified aircraft (n = 1,063) with an age-matched group of pilots who flew other types of aircraft (n = 2,126). Of the two groups, control pilots at ages 21-26 had a significantly higher mortality rate for aviation-related injuries and a higher hospitalization rate for the diagnostic category of accidents, poisonings, and violence. Their hospitalization rates also were significantly higher than pilots of electronically modified aircraft for mental disorders at ages 27-32 and supplementary classifications at ages 39-44. Significant age-specific increases in rates were observed for cardiovascular disease and alcoholism in the control group whereas no significant increases were noted for pilots of electronic models. Pilots in the latter group had low rates for conditions postulated as related to radiation exposure. Such results indicated that pilots of electronically modified aircraft were not at increased risk for illness or injury because of the aircraft models they primarily flew. PMID- 3345180 TI - Management control of aeromedical evacuation systems. AB - Aeromedical evacuation has been extensively used by military forces for evacuation of wartime casualties, but has also proven useful in civilian disaster response. In contrast to the broad coverage of the clinical aspects of the aeromedical evacuation, the operational and management control issues have rarely been addressed. The sophisticated battlefield of the 1980s has had an impact also in air evacuation, adding to the factors to be considered before launching an evacuation mission. The professional control of aeromedical evacuation is, therefore, crucial to the efficient and smooth operation of this high-cost resource. In an attempt to shed light on some of the operational perspectives of military air evacuation, the Israeli experience in the management control of such systems is discussed. PMID- 3345181 TI - Anti-G straining maneuver incompatibility with tactical aircraft oxygen systems. AB - A spectrum of clinical symptoms consisting of grey-out, black-out, and G-induced loss of consciousness has been identified in pilots of high performance aircraft. The M-1 maneuver used in conjunction with reclined seats and inflated G-suit provides significant protection against these symptoms. Centrifuge-trained United States Navy tactical aircraft pilots have recently reported a decreased ability to perform the M-1 maneuver while using the MBU-12P oxygen mask and CRU-79/P oxygen regulator. This report reviewed the performance specifications of these devices and compared them with published pulmonary flow rates. We found this oxygen system to interfere with the performance of the M-1 and other anti-G maneuvers. Further research is needed to characterize pulmonary flow rates during the performance of the M-1 maneuver in order to make recommendations for breathing system standards aboard high performance aircraft. PMID- 3345182 TI - Biophysical evaluation of footwear for cold-weather climates. AB - Proper selection of footwear for cold-wet environments is important in determining individual performance and comfort. Testing only total dry insulation (It) is not a wholly adequate basis for boot selection. The present study demonstrates an effective method for evaluating the effects of surface moisture on boot insulation. This method allows a more knowledgeable selection of footwear for cold-wet climates. In this study, regional insulation values were obtained under dry conditions, then during a soak in shallow water, and finally for insulation recovery after removal from water. Results for seven boots show no advantage of presently used synthetic materials during short soak episodes. Insulated leather-synthetic boots, however, recovered to dry insulation levels more rapidly than more traditional insulated leather boots. Rubber waterproof bottoms were the most effective boot construction for retaining insulation levels during water exposure. PMID- 3345183 TI - Cases from the aerospace medicine residents' teaching file. Case #22. An air traffic controller with syncope and accelerated idioventricular rhythm. AB - An 18-year-old air traffic controller fainted while running; an asymptomatic accelerated idioventricular rhythm was discovered in the ensuing aeromedical workup. The clinical presentation, ECG diagnosis, and aeromedical disposition of accelerated idioventricular rhythm are discussed. PMID- 3345184 TI - Mental health factors in spaceflight. PMID- 3345186 TI - Pars compacta of the sexually dimorphic area of the gerbil hypothalamus: postnatal ages at which development responds to testosterone. AB - The sexually dimorphic area (SDA) of the gerbil hypothalamus contains a dense cell group in males, the SDA pars compacta (SDApc), that is absent in females and that develops under the influence of testosterone. To determine how long SDApc development remains sensitive to testosterone and if it can be fully masculinized, female gerbils were injected with testosterone propionate on various days after birth. Control females and males received the vehicle. SDApc development was assessed when subjects were 2 weeks old. Exposing females to testosterone before they were 3 days old increased both the incidence and the size of the SDApc. Delaying exposure until 3 days after birth prevented these effects. In females that received testosterone daily for 5 days, starting on the day they were born, the incidence and size of the SDApc were the same as in males. PMID- 3345185 TI - Psychoneurogenic stress influences upon retention of an inhibitory avoidance response in the rat. AB - Hormones and peptides involved in the response of an organism to stress play a modulating role in learning and memory processes. We studied whether psychoneurogenic stressors such as sound stimulation or novelty influence retention of an inhibitory avoidance response. An impairing effect on retention was observed when these stressors were applied shortly after the acquisition trial, but not after a 3-h delay. However, sound stimulation and novelty applied shortly before the retention test may facilitate retention behavior. It is suggested that the effect of psychoneurogenic stressors on retention behavior may be linked to influences on consolidation and retrieval processes mediated through the neurohumoral response of the organism to stress. PMID- 3345187 TI - Mice: the initiation and maintenance of pregnancy-induced aggression following thelectomy. AB - Two experiments were conducted in order to assess the effects of thelectomy (i.e., nipple removal) on the display of pregnancy-induced aggression in Rockland Swiss (R-S) albino mice. Pregnant animals, thelectomized on Gestation Day (GD) 12, exhibit a high incidence and intensity of aggression toward adult R-S male intruders during tests conducted on GDs 14, 16, and 18 (i.e., during the last third of gestation in this species). Since thelectomized dams display levels of aggression (i.e., 63% incidence) equivalent to those of sham-operated and nonoperated animals (53 and 67% incidence, respectively), it would appear that nipple presence is not a critical factor for the maintenance of pregnancy-induced aggression in mice (Experiment 1). To examine the effects of nipple deprivation on the initiation of pregnancy-induced aggression, virgin animals were thelectomized prior to mating, then repeatedly tested for aggression at 2-day intervals of gestation. Unlike nipple-intact dams, pregnant mice, deprived of nipples prior to conception, rarely exhibit (less than 17% incidence) agonistic behaviors toward intruder males (Experiment 2). These findings suggest that the development and self-stimulation of nipples early in pregnancy may be important conditions for the display of heightened aggression with advancing pregnancy in mice. PMID- 3345188 TI - Open-field behavior of one-clip, two-kidney hypertensive rats: the influence of pre-handling. AB - The relation between the development of hypertension and changes in behavior was investigated. Hypertension was induced by unilateral application of a 0.20-mm clip around the renal artery. At 4 weeks, but not at 1 week, after the operation an increase in ambulation was found. Blood pressure was significantly increased at 1 (28 mm Hg) and 4 weeks (78 mm Hg) after the operation. In a second experiment, renal hypertensive rats and controls were either regularly handled (i.e., subjected to indirect tail-cuff blood pressure measurements) or left undisturbed. At 4 weeks after clip implantation, only in the nonhandled rats with renal hypertension, an increase in open-field ambulation was found. Blood pressure was markedly increased in both handled and nonhandled renal hypertensive rats. PMID- 3345189 TI - Role of neonatal androgens in sexual differentiation of brain structure, scent marking, and gonadotropin secretion in gerbils. AB - Gerbils display a sexually dimorphic scent marking behavior that responds to testosterone (T) in adulthood and develops under the influence of testosterone perinatally. A complex of cell groups between the preoptic area and anterior hypothalamus of the gerbil brain is also sexually dimorphic and responsive to testosterone. One of these cell groups, the sexually dimorphic area pars compacta (SDApc), usually exists only in males. Even when given testosterone, adult female gerbils rarely have an SDApc. To determine if the SDApc develops under the influence of testosterone, male gerbils were castrated or given sham operations on the day they were born or 1 day later, or were not manipulated. Female gerbils were injected subcutaneously with 0, 50, or 100 micrograms testosterone propionate (TP) on the day after birth. When given ovarian transplants as adults, neonatally castrated males scent marked at low levels typical of females. Neonatally androgenized females given testosterone as adults scent marked at high levels typical of males. Neonatal castration did not affect the probability that the SDApc would develop, but neonatal androgenization did. Half the females given either dose of TP as neonates had SDApcs bilaterally. The sizes of the SDApcs present in females depended on the dose of testosterone given neonatally. The larger dose produced larger SDApcs. The 100-micrograms dose of TP also defeminized gonadotropin secretion, but the 50-micrograms dose did not. The castration of males neonatally prevented the defeminization normally caused by endogenous testosterone. Both groups of neonatally castrated males formed corpora lutea in their ovarian transplants, but control males did not. PMID- 3345190 TI - Responsivity to pain in rats changed by the ingestion of flavored water. AB - Sprague-Dawley male rats drank flavored water and subsequent pain responsivity was assessed using a hot plate first after isotonic saline and later after either 2.75 (Experiment 1) or 2.5 (Experiment 2) mg/kg of morphine hydrochloride was injected. A 48-h exposure to any one of several different flavors resulted in a reduction of the analgesic effects of morphine as shown by an attenuation of the increased latency to paw lick caused by the morphine. This effect was independent of the amount consumed. A 26-h exposure to a flavor decreased pain reactivity before and after morphine as shown by an overall increase in latency to paw lick. This effect was not influenced by whether the normally preferred flavor was made aversive by a previous pairing with lithium chloride-induced illness. These findings are consistent with the idea that many flavors, independently of palatability and amount consumed, increase the release and utilization of endogenous opioids. PMID- 3345191 TI - Novelty-induced opioid analgesia in deer mice (Peromyscus maniculatus): sex and population differences. AB - Exposure to a new environment elicited significant, naloxone (1.0 mg/kg) reversible analgesic responses in three different populations of deer mice; Peromyscus maniculatus artemisiae from the mainland, and P. m. angustus and P. m. triangularis from small marine islands. In all cases male deer mice displayed significantly greater levels of analgesia than females. In addition, the levels of analgesia were significantly greater in the insular than in the mainland populations. These results indicate that there are substantial sex and population differences in the novelty-induced analgesia displayed by natural and laboratory populations of deer mice. PMID- 3345192 TI - The effect of scopolamine and physostigmine on working and reference memory in pigeons. AB - A comparison of the effects of scopolamine and physostigmine on working memory and reference memory in White Carneaux pigeons was undertaken. In Experiment 1, the pigeons received injections of scopolamine hydrobromide (0.03 mg/kg), or saline. Scopolamine hydrobromide had greater disruptive effects on working memory trials than on reference memory trials, and the centrally active form of scopolamine disrupted working memory trial accuracy more than the peripherally active form. The differential sensitivity of accuracy on working memory trials to disruption by central cholinergic blockade was obtained even though the discrimination required on reference memory trials was more difficult. In Experiment 2, the pigeons received injections of scopolamine hydrobromide (0.015 mg/kg), physostigmine (0.075 mg/kg) both scopolamine and physostigmine, or saline. Physostigmine given with scopolamine was able to reverse the scopolamine induced reduction of accuracy on working memory trials. In neither study did scopolamine promote accelerated forgetting as the delay interval was increased. These results indicate that manipulation of central cholinergic neurotransmitter systems influences working memory processes in the pigeon, but these effects occur without alterations in the ability of the birds to actively maintain information during the retention interval. PMID- 3345194 TI - Effects of telencephalic ablation on habituation of arousal responses, within and between daily training sessions in goldfish. AB - Goldfish Carassius auratus were presented with a moving shadow stimulus at 2-min intervals and their cardiac and ventilatory responses were monitored. Normal fish, fish with their telencephalon ablated, and those with sham operations were compared for responsiveness and habituation to repeatedly presented stimuli over the 3-day test period. While all groups showed increased habituation on successive days testing, fish with their telencephalon ablated showed significantly slower response habituation within the daily test sessions when compared with the control groups. Subjects with their telencephalon ablated also showed a tendency for increased responsiveness on initial stimulus presentation and poorer retention between days of information relating to the eliciting test stimulus. PMID- 3345193 TI - Antagonism of behavioral effects of bromocriptine by prolactin in female cats. AB - The effects of the dopaminergic agonist bromocriptine (BC) and exogenously administered prolactin (PRL) on the spontaneous behavior of female cats were investigated. The objective was to test whether BC-induced behavioral effects may be antagonized by PRL. BC (6 mg/kg ip) administration induced abnormal behaviors such as limb flicks, abortive grooms, head/body shakes, and hallucinatory-like behavior/escape as well as excessive grooming. PRL (5 mg/kg ip) administration induced biphasic changes in grooming. The first change was an increase in grooming frequency averaging 256% of baseline control values and lasting for 1 h. This change was followed by reductions in grooming of 75 and 82.5% below baseline during Hours 2 and 3 postinjection, respectively. Combined BC and PRL treatment antagonized the frequency of BC-induced motor effects such as limb flicks, abortive grooms, and head/body shakes. Limb flicks occurred nine times more often 2 h after BC alone than after BC and PRL. The combined treatment also antagonized the excessive grooming observed after separate administrations of BC and PRL. The observed interactions between PRL and BC behavioral effects support the notion that PRL may be an important modulator of dopamine-dependent motor behavior in female cats. PMID- 3345195 TI - Singleness of action in the interactions of feeding with other behaviors in Hermissenda crassicornis. AB - Singleness of action in the interactions of feeding behavior with other behaviors was studied in Hermissenda crassicornis. In Experiment 1 withdrawal of the oral veil from a tactile stimulus was inhibited during feeding elicited by application of a mussel homogenate to hungry animals. Rolling-over behavior was also inhibited during feeding. When animals were satiated, thereby abolishing the feeding response to mussel homogenate, withdrawal occurred in the presence of the food stimulus; however, rolling-over behavior was still inhibited. In Experiments 2 and 3 it was demonstrated that spontaneous locomotion was also inhibited in hungry animals by food stimuli; however, satiated animals ignored the food stimulus and continued to locomote. Both biting behavior and the suppressive effect of food stimuli on locomotion were also observed in dissected anterior ends of Hermissenda, suggesting that the mechanisms underlying the interaction of feeding with other behaviors may be accessible to study in the nervous system of reduced preparations. PMID- 3345196 TI - Stimulation of the conjugation of lipid dienes in hepatic microsomes by 3,3' dichlorobenzidine. AB - Pretreatment of male rats with 3,3'-dichlorobenzidine (DCB) resulted in the accumulation of conjugated dienes in lipids from hepatic microsomes. In vitro, these microsomes had 2-fold the NADPH-dependent malondialdehyde (MDA)-forming capacity of microsomes from untreated rats. To determine the mechanisms of the DCB-induced accumulation of diene conjugation, the effects of added DCB on NADPH- or iron + ascorbic acid- (Fe2+-ascorbate-) dependent diene conjugation, oxygen uptake and MDA formation were examined in microsomes from untreated rats in vitro. In the presence of NADPH, added DCB stimulated diene conjugation in microsomal lipids as did in vivo DCB pretreatment but inhibited the uptake of oxygen and the formation of MDA. When Fe2+-ascorbate was substituted for NADPH, the formation of diene conjugation, oxygen uptake, and MDA formation were inhibited by added DCB. The DCB-induced stimulation of diene conjugation, in addition to being strictly NADPH dependent, was carbon monoxide sensitive and was concomitant with the binding of added DCB to microsomal lipids. It is postulated that a metabolite of DCB generated by cytochrome P-450 reacts with membrane lipids both in vivo and in vitro in a manner analogous to the initiation of lipid peroxidation but at the same time prevents the autocatalytic decomposition of the lipids. The DCB-induced diene conjugation is interpreted as predisposing to deleterious changes in microsomes. PMID- 3345197 TI - Lack of evidence for a hepatic peroxisome proliferator receptor and an explanation for the binding of hypolipidaemic drugs to liver homogenates. AB - The existence of a postulated hepatic receptor responsible for the peroxisomal proliferation induced in rodents by hypolipidaemic drugs has been investigated. [3H]-nafenopin and [3H]-ciprofibrate were used as labelled ligands and two competitive binding assays, using either a charcoal-dextran or a hydroxylapatite method, were developed to investigate potential binding. In both assay systems, specific displaceable binding of either nafenopin or ciprofibrate to whole homogenate, microsomal and cytosolic fractions of rat liver could not be detected in a variety of buffer systems. A positive control of ligand binding to bovine serum albumin indicated the validity of the binding assays used. In addition, both nafenopin and ciprofibrate exhibited displaceable binding to serum albumin using the hydroxylapatite binding assay and a Scatchard analysis of the binding of [3H]-nafenopin to fatty acid free rat serum albumin yielded a dissociation constant of 5.2 x 10(-7) M and 86 pmol of ligand bound per mg protein. Taken collectively, our data strongly argues against the existence of a specific hepatic peroxisome proliferation receptor and indicates that the peroxisome proliferating hypolipidaemic drugs bind to serum albumin and possibly to other cellular proteins not involved in the activation of genes necessary for peroxisome proliferation. PMID- 3345198 TI - Na+-independent release of Ca2+ from rat heart mitochondria. Induction by adriamycin aglycone. AB - The effect of adriamycin aglycones on Ca2+ retention by isolated, preloaded rat heart mitochondria was assessed. After an initial lag, which decreased with increasing drug concentration, the 7-hydroxy-aglycone (5-20 microM) triggered Ca2+ release. Aglycone-induced Ca2+ release was correlated with Ca2+-dependent mitochondrial swelling, Ca2+-dependent collapse of the mitochondrial membrane potential, Ca2+-dependent oxidation of mitochondrial pyridine nucleotides, and a transition from the condensed to the orthodox configuration. Aglycone-induced Ca2+ release was inhibited by dibucaine, dithiothreitol, ATP, and bovine serum albumin. It can be concluded, therefore, that aglycone-induced Ca2+ release reflects the Ca2+-dependent increase in the permeability of the inner mitochondrial membrane to solutes of molecular weight less than 1000 which has been observed with other triggering agents [R. A. Haworth and D. R. Hunter, Archs Biochem. Biophys. 195, 460 (1979); I. Al-Nasser and M. Crompton, Biochem. J. 239, 19 (1986)]. In particular, the 7-hydroxy-aglycone decreased the amount of Ca2+ required to trigger the permeability increase. No effect of the aglycone on Ca2+ uptake could be discerned. 7-Deoxy-adriamycin aglycone, the more prominent biological metabolite of adriamycin, was similarly effective in inducing Ca2+ release, and both aglycones were substantially more effective than the parent drug. Adriamycin and related anthracyclines are potent antineoplastic agents, the clinical use of which is limited by severe cardiotoxicity. These results suggest that aglycone formation and the resultant disruption of both cellular Ca2+ homeostasis and metabolite compartmentation may mediate anthracycline cardiotoxicity. PMID- 3345199 TI - Effects of some mono- and bisquaternary ammonium compounds on the reactivatability of soman-inhibited human acetylcholinesterase in vitro. AB - Acetylcholinesterase (AChE) inhibited by the organophosphate soman (1,2,2 trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex. This reaction is called aging. The effect of the four mono- and bisquaternary ammonium compounds tetramethylammonium (TMA), hexamethonium, decamethonium and suxamethonium on the reactivatability of soman-inhibited, solubilized AChE from human erythrocytes was investigated in vitro. All compounds were reversible inhibitors of AChE; the respective dissociation constants and the type of inhibition exhibited considerable differences. The affinities to both the active and the allosteric site were considerably higher for suxamethonium (Kii 81.3 microM; Ki 15.9 microM) and decamethonium (Kii 15.4 microM; Ki 4.4 microM) than for TMA (Kii 1 mM; Ki 289.6 microM) and hexamethonium (Kii 4.5 mM; Ki 331.8 microM). The reactivation experiments were performed in a four-step procedure (soman-inhibition at 0 degree and pH 10, aging at 37 degrees and pH 7.3, reactivation by the oxime HI 6 at 37 degrees and pH 7.3 followed by AChE assay). After these four steps (total duration 55 min), AChE was inhibited by soman to 95 100%. HI 6 could reactivate about 20% of the inhibited enzyme. All effectors increased the AChE reactivatability by HI 6 when added before aging was started. The maximal increase in reactivatability was higher in the presence of 1.6 mM suxamethonium (+35.8%) and 150 microM decamethonium (+40%) than of 22 mM TMA (+22.5%) and 8.3 mM hexamethonium (+19.2%). If the effectors were added after 5 min of aging they increased the activity of soman-inhibited AChE, but to a considerably smaller extent than HI 6. A good correlation of the respective Kii values and the effective concentrations of these drugs was observed, indicating that an allosteric binding site of AChE might be involved in the protective effect of these drugs. PMID- 3345201 TI - Promotion of cystine uptake and its utilization for glutathione biosynthesis induced by cysteamine and N-acetylcysteine. AB - Chinese hamster ovary (CHO) cells obtain a high capacity to utilize cystine from the growth medium by exposure to cysteamine (2-mercaptoethylamine, MEA) or N acetylcysteine (NAC). For uptake studies a modified McCoy's 5A medium supplemented with 0.1 mM [35S]cystine was used. The uptake of cystine was dependent on the time of exposure (0-60 min) and the concentrations of MEA or NAC (0-8 mM). At high concentrations of MEA or NAC, the uptake of cystine became saturated. Half-maximal uptake of cysteine was observed at concentrations of 0.12 mM MEA and 0.66 mM NAC, respectively. Increase in temperature (37-44 degrees) or pH (6.0-8.0) during MEA or NAC exposure further increased the cystine uptake. The increased uptake of cystine was not affected in the presence of glutamate or homocysteate which both inhibited the cystine uptake of control cells. Determination of both reduced (GSH) and oxidized (GSSG) cellular glutathione showed a twofold increase in MEA- or NAC-treated CHO cells. DL-buthionine-S,R sulfoximine (BSO), an inhibitor of GSH biosynthesis completely blocked the promotion of cystine uptake by MEA and NAC. By further analysis using reversed phase HPLC of cell extracts, more than 90% of the [35S] radioactive cystine taken up by the cells could be recovered within the pool of GSH. The results demonstrate that exposure of CHO cells with MEA and NAC leads to a promoted uptake of cystine from the culture medium and its rapid utilization for cellular GSH biosynthesis. PMID- 3345200 TI - Enzymic programs of rat bone marrow and the impact of acivicin and tiazofurin. AB - The in vivo actions of two antimetabolites, acivicin (NSC-163501) and tiazofurin (NSC-286193), were examined on the enzymic programs of rat bone marrow. From the bone marrow of the femurs, 100,000 g supernatant fractions were prepared; enzymic activities were measured by isotopic assays, and cellularity was determined. In the normal bone marrow, the specific activities of pyrimidine de novo synthetic enzymes, CDP reductase, dTMP synthase, CTP synthase, carbamoyl-phosphate synthase II (synthase II), orotidine 5'-phosphate decarboxylase and aspartate carbamoyltransferase, were 1, 2.7, 5, 10, 63 and 601 nmol/hr/mg protein, respectively, whereas those of the salvage enzymes, deoxycytidine, thymidine, cytidine and uridine kinases were 3, 43, 149, and 367 nmol/hr/mg protein, respectively. In purine biosynthesis, the activities of the de novo synthetic enzymes, IMP dehydrogenase, formylglycinamidine ribonucleotide (FGAM) synthase, GMP synthase, amidophosphoribosyl-transferase (AT) and adenylosuccinate synthase were 16, 8, 107, 78 and 124 nmol/hr/mg protein, respectively, and those of the salvage enzymes, adenine, hypoxanthine and guanine phosphoribosyl-transferases, were 340, 407, and 1018 nmol/hr/mg protein, respectively. The sequence of events was elucidated after a single i.p. injection of acivicin (5 mg/kg) or tiazofurin (200 mg/kg). Within 2 hr after acivicin injection, CTP, GMP and FGAM synthases lost 85-90%, while AT and synthase II lost 50 and 80%, respectively, of their activities. The activities rose to near normal range by 72-96 hr. The bone marrow cellularity decreased, reaching a nadir at 24 and 48 hr, and returning to normal range by 72 and 92 hr; thymidine kinase activity followed a similar pattern. Tiazofurin injection depressed IMP dehydrogenase activity to 20% by 2 hr with a rebound to normal range by 48 and 72 hr. The cellularity decreased more slowly, reaching its lowest point at 24 hr and returning to normal range at 72 hr. For acivicin the marked depletion of the activities of the glutamine-utilizing enzymes and for tiazofurin that of IMP dehydrogenase might account, in part at least, for the bone marrow toxicity of these antimetabolites. Because of the presence in the bone marrow of high activities of purine and pyrimidine salvage enzymes, it should be possible to design methods utilizing nucleosides and nucleobases to protect the bone marrow from the action of antimetabolites. PMID- 3345202 TI - Tissue distribution and warfarin sensitivity of vitamin K epoxide reductase. AB - The distribution of vitamin K epoxide reductase activity and its sensitivity to warfarin have been examined in whole microsomes from tissues of both control and warfarin-resistant strain rats. The distribution of activity roughly paralleled that previously shown for the vitamin K-dependent carboxylase. Activity on a per gram tissue basis was highest in kidney, adrenal, spleen, lung, testes, and epididymis at a level about 1/20th of that present in liver microsomes. Vitamin K quinone formation by microsomes from warfarin-resistant rats was approximately half that of control strain samples. In addition, hydroxy vitamin K was formed by warfarin-resistant strain microsomes to about the same extent as vitamin K quinone in all tissues. The Km values for dithiothreitol (DTT) and vitamin K epoxide were similar in all tissues (range = 0.1-0.2 mM DTT at 40 microM vitamin K epoxide, and 10-30 microM vitamin K epoxide at 2 mM DTT). The sensitivities to warfarin were similar for all control strain rat tissues (I50 = 10-20 microM at 2 mM DTT and 40 microM vitamin K epoxide) and similarly elevated for all warfarin resistant rat tissues (I50 = 30 to greater than 80 microM). These results suggest that the identical enzyme is expressed in all tissues and that tissue specific isozymes do not occur. PMID- 3345203 TI - Age-dependent decrease in the hepatic uptake and biliary excretion of ouabain in rats. AB - The biliary excretion of i.v. injected ouabain was examined in male and female Wistar-derived rats in relation to age. The hepatic uptake velocity for ouabain was also determined in isolated hepatocyte preparations obtained from male rats of various ages. Biliary recovery values of ouabain (percent of the dose) were fairly comparable for young male and female rats (3-4 month old). Recovery progressively decreased with age, the first 10-min recoveries at 24 months being about one-third those of respective young values in both sexes. A significant linear relation was demonstrated between the first 10-min recovery (Y, percent of the dose) and rat age (X, month), yielding the relations of Y = 17.75-0.43X for males and Y = 18.99-0.43X for females respectively. Similarly, the initial uptake velocity (Y, nmol/mg/min) for ouabain decreased in a linear fashion with age (X, month), yielding a significant negative correlation (Y = 0.704-0.0021X, r = 0.839, P less than 0.005, N = 21) at an ouabain concentration of 8 microM. Kinetic studies using non-linear regression analysis revealed a significantly lower Vmax value (0.533 +/- 0.041 nmol/mg/min) in old (24-29 months) rats compared to the young (4-4.5 months) value (1.193 +/- 0.105 nmol per mg/min, P less than 0.05), while the affinity constant (Km, microM) did not differ significantly between young and old animals (203.12 +/- 25.42 microM in young rats vs 283.68 +/- 28.90 microM in old rats, mean +/- SE, 0.05 less than P less than 0.1). The results of the present study suggest that the age-dependent decrease in the biliary recovery of i.v. injected ouabain in rats can be largely explained by the decrease with age in the hepatic uptake of ouabain. Furthermore, the results provide further support for our previous thesis that the decrease in the lateral mobility of hepatocyte plasma membrane proteins, as revealed by the fluorescence recovery after photobleaching technique, may play a significant role in the age-dependent decrease in the physiological function(s) of the hepatocyte plasma membrane, such as the hepatobiliary transport of ouabain. PMID- 3345204 TI - Inhibition of protein kinase C by defensins, antibiotic peptides from human neutrophils. AB - Defensins, human neutrophil peptide (HNP) antibiotics, potently inhibited phospholipid/Ca2+ protein kinase (protein kinase C, PKC) and phosphorylation of endogenous proteins from rat brains catalyzed by the enzyme. Of the three defensin peptides, HNP-2 appeared to be more potent than HNP-1 and HNP-3. Kinetic studies indicated that defensins inhibited PKC noncompetitively with respect to phosphatidylserine (a phospholipid cofactor), Ca2+ (an activator), ATP (a phosphoryl donor) and histone H1 (a substrate protein) with Ki values ranging from 1.2 to 1.7 microM. Defensins, unlike polymyxin B (another peptide inhibitor of PKC), did not inhibit the binding of [3H]phorbol 12,13-dibutyrate to PKC; however, defensins, like polymyxin B, inhibited the PKC activity stimulated by 12 O-tetradecanoylphorbol-13-acetate. Defensins had little or no effect on myosin light chain kinase (a calmodulin/Ca2+-dependent protein kinase) and the holoenzyme or catalytic subunit of cyclic AMP-dependent protein kinase, indicating a specificity of action of defensins. It is suggested that defensins, among the most potent peptide inhibitors of PKC so far identified, may have profound effects on functions of neutrophils and other mammalian cells, in addition to their well-recognized antimicrobial activities. PMID- 3345205 TI - Enhanced uptake of spermidine and methylglyoxal-bis(guanylhydrazone) by rat liver mitochondria following outer membrane lysis. AB - Isolated rat liver mitochondria rapidly bound the 14C-labeled organic cations spermidine, a physiologically important polyamine, and methylglyoxal bis(guanylhydrazone) (MGBG), an anticancer drug. This rapid, Mg2+-sensitive, respiration-independent binding is assumed to involve adsorption to anionic surface groups. A slower progressive uptake of the organic cations exhibited respiration dependence, indicating that it involves transport across the inner mitochondrial membrane into the matrix compartment. Addition of digitonin, to lyse the outer mitochondrial membrane, caused an increase in the mitochondrial content of the organic cations and enhanced the rate of progressive, respiration dependent cation uptake. The data are consistent with the interpretation that the outer mitochondrial membrane limits access of the organic cations, spermidine and MGBG, to the inner mitochondrial membrane. This conclusion is supported also by published data indicating that outer membrane lysis enhances inhibitory effects of the organic cations on mitochondrial respiration. The uptake of spermidine by mitochondria was inhibited by MGBG. PMID- 3345206 TI - Effect of hypoxic perfusion on hepatic concentration and biliary release of glutathione disulfide. PMID- 3345207 TI - Ketamine protects acetylcholinesterase against in vitro inhibition by sarin. PMID- 3345208 TI - [3H]quinuclidinyl benzilate binding to the human lung muscarinic receptor. PMID- 3345209 TI - Time- and dose-dependent inhibition of erythrocyte glutathione peroxidase by cisplatin. PMID- 3345211 TI - B16 melanoma development in black mice exposed to low-level microwave radiation. AB - The effect of low-level microwave exposure, 2,450 MHz, at a power density of 1 mW/cm2 and specific absorption rate of 1.2 mW/g, continuous waves (CW) or pulsed waves (PW), 2.5 h/day, 6 sessions/week until death (up to 690 h of irradiation), has been studied in black C57/6J mice with B16 melanoma. The results show that no significant effects are observed on tumor development or on survival times compared to controls, or between CW- and PW-treated animals. PMID- 3345210 TI - Current densities induced in swine and rat models by power-frequency electric fields. AB - Measurements have been made of vector current densities induced by vertical, uniform, 60-Hz electric fields in the torsos of homogeneous models of swine and rats. The observed data were a strong function of the five grounding configurations invested: all four feet grounded, only front feet grounded, only rear feet grounded, left front and right rear feet grounded, and right front and left rear feet grounded. In the first configuration and with an exposure field strength of 10 kV/m, average total current densities induced in the torsos of pigs and rats were 34 nA/cm2 and 20 nA/cm2, respectively. The corresponding value for human exposure is about 250 nA/cm2, 7.3 and 12.5 times larger than for swine and rats, respectively. Current densities measured at 60 Hz can be linearly extrapolated to frequencies in a range extending from at least 1 Hz to 1 MHz. Human and animal current-density data can provide an improved rationale for extrapolating biological data across species. In addition, these data can be used to validate the predictions of numerical models. PMID- 3345212 TI - A strong static-magnetic field alters operant responding by rats. AB - Forty male rats of the Wistar ST strain were trained and observed for Sidman avoidance (SA) for 7 weeks or for discriminative avoidance (DA) for 14 weeks to determine the effects of exposure to a strong static-magnetic field. Before avoidance conditioning was completed, rats in the SA group were exposed to the static field at 0.6 T, 16 h/day for 4 days during the fifth week, and those in the DA group were exposed for 6 h/day for 4 days during the seventh week. In the SA conditioning, frequency of lever-pressing by exposed rats gradually decreased during 1 week of exposure and stayed low for at least 2 weeks after exposure. Frequencies of electric shocks received by the rats increased dramatically during the second day of exposure and consistently stayed higher than those of control rats. In the DA condition, exposed rats responded at lower rates than did control rats throughout the observation period. They received more shocks during the 2 weeks following exposure. The data indicate that performance of avoidance responses was inhibited by a comparatively long exposure to a strong magnetic field. PMID- 3345213 TI - Effects of pulsed extremely-low-frequency magnetic fields on skin wounds in the rat. AB - Rats with skin-wounds surgically created on their backs were exposed immediately after surgery and every 12 h thereafter to pulsed, extremely-low-frequency magnetic fields. The shape of the pulse was a positive triangle (50 Hz, 8 mT peak). The rate of healing of skin wounds was evaluated macroscopically and by light and electron microscopy at 6, 12, 21, and 42 days after the operation. A significant increase in the rate of wound contraction was found in rats treated with magnetic fields. Forty-two days after surgery all treated animals show fully closed wounds, while control rats at the same time intervals still lacked a final 6% of the wound surface to be covered. Treated rats showed earlier cellular organization, collagen formation and maturation, and a very early appearance of newly formed vascular network. PMID- 3345214 TI - Microwave attenuation of ethanol-induced hypothermia: ethanol tolerance, time course, exposure duration, and dose response studies. AB - Four experiments were conducted to quantify the reported attenuation by microwave (MW) irradiation of ethanol-induced hypothermia. In one experiment rats were irradiated (continuous wave 2.45 GHz, specific absorption rate = 0.3 W/kg) or sham irradiated for 45 min, injected with 3.6 g/kg, 20% (v/v) ethanol (EtOH) or saline (NaCl) i.p.. Colonic temperature was monitored at 20-min intervals for 2 h. This procedure was repeated for 8 days to determine the rate of tolerance development to the hypothermic effect of ethanol. While MW irradiation did significantly attenuate EtOH-induced hypothermia, it did not enhance or retard the rate of tolerance development. To determine the duration of irradiation necessary to attenuate EtOH-induced hypothermia, groups of rats were irradiated or sham irradiated for 5, 15, 30, or 60 min prior to EtOH injection and subsequent temperature measurements. The attenuation was apparent only after 60 min of irradiation. To determine the duration of the attenuation effect after irradiation, rats were injected with EtOH or NaCl at 0, 30, 60, 120, or 480 min after 45 min of irradiation or sham irradiation. The attenuation effect was apparent among rats injected 0 to 30 min after irradiation and for the first 40 min for groups injected at 120 min. Additional rats were injected with NaCl or 0.9, 1.8, or 2.7 g/kg of EtOH i.p. following 45 min of irradiation or sham irradiation to determine if the attenuation effect depends on the dose of EtOH administered. Attenuation of EtOH-induced hypothermia was more apparent at lower doses of EtOH than at higher doses. These results indicate that the effect is an acute response to irradiation, and rule out several other potential explanations. PMID- 3345215 TI - Comparative study of shortwave heating patterns in phantoms with polyethylene and silk partitions. AB - Specific absorption rate (SAR) and effective depths of heating patterns induced by a shortwave, pancake diathermy applicator in fat-muscle phantom are measured. Midplane partitions of polyethylene and silk screen with and without contact chemicals are used. Thermographically obtained SAR data show nearly the same value for silk-screen partitions with and without contact chemicals and slightly lower values with polyethylene partitions, provided that the partition midplanes are tightly pressed against each other. Thermometry data indicate that for low power exposures the major error in thermographic measurements obtained after termination of heating is due to thermal diffusion and not evaporative cooling in the opened midplane of the phantom. PMID- 3345216 TI - Measurements of housing density along transmission lines. AB - One of the fundamental inputs to models of population exposure to the power frequency fields of high-voltage transmission lines is the density of population about the lines. We examined aerial photographs of over 1,700 km of transmission corridor to characterize the density of nearby housing units. The data show that the density of houses within 200 m of transmission lines 1) is typically smaller than the average density of houses in the local utility's service area, 2) tends to increase with distance from the line, and 3) is inversely correlated with line voltage. PMID- 3345217 TI - Development of young rats and rabbits exposed to a strong electric field. AB - Body growth and circulating levels of hormones were assessed in young rats and rabbits exposed to a 50-Hz electric field of 50 kV/m. Eight-week-old male rats were exposed 8 h/day for 4 weeks and rabbits were exposed 16 h/day from the last 2 weeks of gestation to 6 weeks after birth. The body and the organ growth of exposed rats were not statistically different from those of sham-exposed controls. No important differences from controls were observed in plasma levels of corticosterone, TSH, ACTH, and T4 or in adrenal levels of epinephrine, norepinephrine, and corticosterone although T3 was slightly, but significantly, decreased. No large histological changes in the thyroid or adrenals were noted. In rabbits, organ and body weights of exposed animals were comparable to those of controls. Plasma levels of various hormones (ACTH, GH, T3, T4, corticosterone, cortisol), serum glucose, triglycerides, and cholesterol were not significantly altered. Adrenal content of cortisol was lower, however, in exposed rabbits. No histological changes of the thyroid or adrenal glands were observed. PMID- 3345218 TI - Osteogenesis imperfecta. A model for genetic causes of osteoporosis and perhaps several other common diseases of connective tissue. PMID- 3345219 TI - HLA and immunoglobulin allotypes in mixed connective tissue disease. AB - A group of patients with mixed connective tissue disease (MCTD) were HLA and immunoglobulin allotyped. We found that the incidence of DR4 in the patient group was increased compared with that in the normal controls, but the increase was restricted to the subgroup of patients with arthritis. The age at onset of MCTD was lower in patients with DR4 and higher in patients with DR2 compared with patients who did not have these antigens. A1, B8, and DR3 were more frequent, but not significantly so, in the MCTD patient group. We also found that there was a significant perturbation of the Gm allotype frequencies in patients with MCTD. PMID- 3345220 TI - A new autoantibody in patients with rheumatoid arthritis: characterization of the anti-HaT-1 antibody system. AB - A unique, new autoantibody, anti-HaT-1, has been identified in the serum of patients with rheumatoid arthritis (RA). Anti-HaT-1 antibody is predominantly IgM, and reacts by double immunodiffusion with HaT-1 antigen, an acidic protein in human and rat liver supernatant (MW approximately 150,000). It was detected in 9 of 38 patients with RA, 2 of 15 patients with RA and Sjogren's syndrome, and none of 92 patients with other connective tissue diseases, indicating that this autoantibody is highly specific for RA. PMID- 3345221 TI - Tertatolol-induced lupus. PMID- 3345222 TI - Thalidomide-induced neuropathy in rheumatoid arthritis patients. PMID- 3345223 TI - The effect of lymphoid irradiation on the progression of joint damage in intractable rheumatoid arthritis. PMID- 3345224 TI - Impotence in scleroderma. PMID- 3345225 TI - Diflunisal-associated thrombocytopenia in a patient with rheumatoid arthritis. PMID- 3345226 TI - Sural nerve biopsy in systemic necrotizing vasculitis. PMID- 3345227 TI - Comment on the article by Lahita et al, on their finding of low plasma androgen levels in systemic lupus erythematosus (SLE) patients. PMID- 3345228 TI - A description of rheumatology practice II. PMID- 3345229 TI - Comment on the article by Hasselbacher on inter-laboratory variation in methods and results of synovial fluid analysis. PMID- 3345230 TI - Clonal proliferation of large granular lymphocytes in rheumatoid arthritis. AB - Some patients with chronically elevated large granular lymphocyte (LGL) numbers have rheumatoid arthritis (RA). Since these patients also may have neutropenia and splenomegaly, their symptoms resemble those of patients diagnosed as having Felty's syndrome (FS). We studied the immunophenotypic and genotypic characteristics of mononuclear cells from patients with RA and neutropenia to better determine the extent of heterogeneity in this condition. Four patients had markedly increased numbers of LGLs, which expressed HNK-1 antigen and IgG Fc receptors. In contrast, the remaining 8 patients, who had FS, had normal LGL counts, and surface marker studies showed normal numbers of HNK-1 and IgG Fc receptor positive cells. Clonal rearrangement of the T cell receptor beta chain gene was demonstrated in all 4 patients with excess LGLs, whereas a germline configuration of this gene was present in all 6 FS patients in whom this was studied. These results suggest that there are diverse groups among patients with RA and neutropenia. Since prognosis may differ, it is important to recognize that some patients who are considered to have Felty's syndrome may have a clonal proliferation of LGLs. PMID- 3345231 TI - Radiographic and joint count findings of the hand in rheumatoid arthritis. Related and unrelated findings. AB - Radiographic and physical joint count findings of the hands and wrists of 148 patients with rheumatoid arthritis (RA) were analyzed in a cross-sectional study. Quantitative radiographic scores for joint space narrowing, erosion, and malalignment were correlated highly with joint count scores for limitation of motion and deformity, and were correlated at considerably lower levels with joint swelling scores. Radiographic scores, however, were not correlated at all with joint count tenderness scores. That 2 of the most widely used indices of RA disease activity, radiographic erosion scores and joint count scores for tenderness, were independent of one another at a selected timepoint, should be considered in the design of clinical trials and long-term observation of patients with RA. PMID- 3345233 TI - Monoclonal rheumatoid factor-IgG immune complexes. Poor fixation of opsonic C4 and C3 despite efficient complement activation. AB - Monoclonal IgM rheumatoid factor forms complexes with IgG in essential mixed cryoglobulinemia. We demonstrate that such complexes fix C3 and C4 poorly, although efficient fluid-phase C3 conversion can occur. Fixation of small amounts of C4 may be sufficient to generate a C3 convertase, but may prevent subsequent fixation of C3 by competing for binding sites on the complex. These complexes bind inefficiently to normal erythrocyte complement receptor type 1 (CR1) in vitro, and are undetectable on erythrocytes of patients with essential mixed cryoglobulinemia in vivo. Clearance of such phlogistic complexes from tissues by CR1-bearing cells may be inefficient. PMID- 3345232 TI - Antioxidant activity of synovial fluid, hyaluronic acid, and two subcomponents of hyaluronic acid. Synovial fluid scavenging effect is enhanced in rheumatoid arthritis patients. AB - To test the scavenging of reactive oxygen species (ROS), we added synovial fluids from patients with rheumatoid arthritis (RA) and osteoarthritis, as well as hyaluronic acid (HA) and its 2 subcomponents, D-glucuronic acid and N-acetyl-D glucosamine, to 2 ROS-generating systems, activated neutrophils and xanthine xanthine oxidase. Synovial fluid from RA patients, HA, and D-glucuronic acid markedly decreased the O2-, H2O2, OH., and chemiluminescence measured in both systems. HA and synovial fluid, which are known to be susceptible to degradation by excessive ROS in RA patients, also seem to play an active role in protecting articular tissues from oxidative damage. PMID- 3345234 TI - CROS revisited. PMID- 3345235 TI - Hear Hear! PMID- 3345236 TI - Electrodiagnosis of diabetic peripheral polyneuropathy. A multivariate analytic approach. AB - Traditional univariate comparisons of nerve conduction data against standard norms may produce conflicting estimates of the presence or absence of a diabetic neuropathy, depending upon the data obtained and the specific nerves sampled. Alternatively, a multivariate analytic approach, using discriminant functions, provides a useful single measure of the degree of neuropathy determined as a weighted combination of the available data. The weights are derived from the linear discriminant function, which maximizes statistical separation of diabetic and nondiabetic subject groups. In this study, 12 electrophysiologic attributes are used to generate a single discriminant function that clearly separates diabetic from nondiabetic subjects and is interpretable as a neuropathic index. Each individual's index of diabetic neuropathy (I) can be quantified as follows: (Formula: see text) where Ai is the original electrophysiologic attribute (i = 12), ai is the coefficient for each attribute that defines the discriminant function and C is a constant specific for that function. For the first time, the degree of diabetic neuropathy can thus be quantified for purposes of comparison and correlation with other quantifiable clinical/somatic measures of diabetes. The index allows for a higher percentage of type II diabetic patients to be classified as neuropathic than previously described and enables determination of degree of neuropathy is affected individuals by an interpolative method. PMID- 3345237 TI - Motor unit analysis. Comparison between concentric and monopolar electrodes. AB - Motor unit action potential (MUAP) measurement parameters are reported to be affected by the type of needle electrode. MUAP amplitude measured with monopolar electrodes has been reported to be up to twice the amplitude recorded with concentric electrodes. We hypothesized that with current technology the difference in recordings from the two needles should be minimal and of little clinical significance. The right extensor digitorum communis muscle was examined in 15 healthy volunteers with first a concentric and then a monopolar needle. The filter band-pass of the electromyograph was 20 Hz to 10 kHz. Four first-recruited MUAPs were isolated by using each electrode. A separate muscle insertion was performed to locate each potential. Amplitudes were maximized. Consecutive MUAPs were averaged and measured. The mean (+/- SD) values of the measurements were as follows: amplitude: monopolar, 1038 (+/- 369) microV; concentric, 912 (+/- 315) microV; duration: monopolar, 10.8 (+/- 2.0) ms; concentric, 9.7 (+/- 1.7) ms. No statistically or clinically significant differences exist between these measurement values. PMID- 3345238 TI - Academic physiatry. An attractive alternative. AB - This presentation will review academic programs and discuss the pros and cons of academic practice. The role of the academic physiatrist in the future and the requirements for improving academic programs will be addressed. Like any other medical specialty, the viability of physical medicine and rehabilitation depends on its acceptance as an academic discipline. In recent years, there has been a number of positive indicators for strengthening academic physiatry including: increased educational exposure to medical students, increased number of residency programs and percentage filled and increased emphasis on research activities. Academic practice of physiatry should appeal to the individual with the following goals in life: (1) increase involvement in scholarly activities; (2) be on the cutting edge of new techniques and concepts of practice; (3) become a recognized expert in subspecialization areas; (4) vary practice more evenly between direct and indirect patient care activities; (5) work in an intellectually stimulating environment but with some constraint on one's destiny; (6) obtain adequate but not high financial rewards supplemented by a high benefit package; and (7) make a significant impact on the future of physical medicine and rehabilitation at the national level. Because academic physiatry will significantly influence the determination of what is rehabilitation and who will practice it, we must strive to improve the quantity and quality of academic programs. Areas especially needing attention are research and education to establish the scientific basis of the field and to train qualified personnel. To meet these goals, high quality clinical and scholarly programs with subspecialization, an adequate financial base and good marketing program will be necessary. PMID- 3345240 TI - Applying leadership skills in conflict management. Synopsis of the AAP program presentation at the 49th annual assembly of the American Academy of Physical Medicine and Rehabilitation, Orlando, Florida, October 1987. AB - This brief paper has reviewed a few of the basic concepts related to the understanding of leadership styles. The unavoidable nature of conflict in organizations has been described. One of the best ways a person can make conflict more manageable is to become increasingly aware of his or her own fundamental leadership style as well as that of others. Without such an effort, people run the risk of moving apart rather than toward a closer working relationship. Regardless of whether an organization is a rehabilitation team, a university faculty or any other group in society, improvements in organizational functioning cannot be made without an awareness of conditions that create conflict. PMID- 3345239 TI - Amitriptyline for post-traumatic agitation. AB - Agitated behavior is exhibited in up to 30% of patients recovering from a traumatic brain injury. Past treatment protocols have included proactive behavioral management and major tranquilizers. We now report the use of amitriptyline for control of agitation. For a period of over 2 years, 43 male and 15 female patients with a "recent" severe brain injury were admitted for inpatient rehabilitation and subjected to traditional structured programming for treatment of post-traumatic amnesia (PTA). In 20 patients, 18 men and 2 women, where agitation persisted sufficiently to impede rehabilitation despite initiation of structure, amitriptyline was instituted. These patients were of a comparable age (29.4 years for the agitated group versus 25.6 years for the nonagitated group), but the agitated patients had a lower median Rancho Los Amigos Hospital Level of Cognitive Functioning in a comparison to nonagitated patients (V versus VI). All patients were monitored for cognitive performance by the Orientation Group Monitoring System, and a daily account of frequency, severity and type of agitation was recorded. Within 7 days of initiation of therapy, 12 of 17 patients within PTA had dramatic decrease in agitation (5/5 patients at Rancho IV; 4/8 at Rancho V; 3/4 at Rancho VI). Two of the three patients at Rancho VII had agitation that was unresponsive to amitriptyline. The amitriptyline-responsive patients were maintained on the drug through PTA, and the Orientation Group Monitoring System scale demonstrated no impedance in cognitive recovery. Thus, amitriptyline appears most useful as an adjunct for treatment of nondirected agitation; it also has a role in reducing the severity of the directed agitation that is seen during but not after PTA. PMID- 3345241 TI - Aluminum-related bone disease. AB - Only rather recently has the biologic and pathogenetic relevance of aluminum, this most common metal come under serious scientific scrutiny. Various laboratory findings of accumulations of aluminum in the brain, kidney, liver, parathyroid glands, skeletal muscle, heart, lungs, pancreas and spleen as well as stainable aluminum in bone have spurred widespread interest in aluminum absorption and toxicity and in the mechanisms involved in the metabolism of aluminum. Since the kidney is the major excretory organ for aluminum, this report focuses on the abnormalities occurring with aluminum accumulation in the bone of patients with renal failure to determine the metabolic interrelationships of aluminum, parathyroid hormone, vitamin D, iron, and calcium. This editorial presents an overview of the most recent investigations of aluminum accumulation in humans, experimental animal models, and at the cellular level, presents the metabolic relationships known to exist as well as those strongly suggested in documented studies, and identifies those aspects of aluminum-related bone disease awaiting study in this increasingly important field of inquiry. The study outlines the metabolism of aluminum, the pathogenesis, prevalence, morbidity and mortality of aluminum-related bone disease, the histopathology of bone with aluminum accumulation, the recognized difficulties inherent in the diagnosis of aluminum related bone disease, and the current understanding as relates to prevention and therapy. PMID- 3345242 TI - Leukocytes, eosinophils and complement function during hemodialysis with polysulphone and polymethylmethacrylate membranes: comparison with cuprophan and polyacrylonitrile. AB - The biocompatibility of the two new dialysis membranes, polysulphone (PS) and polymethylmethacrylate (PMMA), was evaluated versus cuprophan (CUP) and polyacrylonitrile (PAN) by studying the in vivo effects of the four different membranes on leukocyte counts, eosinophil levels and complement function both in the presence and absence of dialysis fluid. Complement function was also examined in vitro by studying the generation of chemotactic factors, whole complement activity and C3d serum conversion. Passive absorption of complement fractions by membranes has completed in vitro studies. PS, PMMA and PAN showed a higher biocompatibility than CUP, even if slight differences can be observed: PS showed a PAN-like biocompatibility pattern with a relatively high absorption of complement factors by the membrane and without complement activation. On the other hand, PMMA showed a CUP-like pattern and caused complement activation, even though to a lower intensity than CUP. PMMA biocompatibility appears to stand in between CUP and the other two synthetic membranes PS and PAN. Our results confirm the important role played by membrane-induced complement activation on hemodialysis leukopenia. Dialysis fluid does not have a significant influence on membrane biocompatibility, but represents the major factor in determining intradialytic eosinopenia. Eosinophils seem to represent a more important marker of dialysis than of membrane biocompatibility. PMID- 3345243 TI - Suction-supported continuous arteriovenous hemofiltration in children. AB - Spontaneous continuous arteriovenous hemofiltration (CAVH) may fail to control azotemia in small patients with renal failure due to poor blood flow. To produce adequate ultrafiltrate a continuous negative pressure was added to the ultrafiltrate line. Two hemofilter systems of different membrane and surface area were used. Suction support approximately doubled ultrafiltration rate in both hemofilters. No side effects such as severe hypotonia or early hemofilter clotting occurred. Added suction can serve as a useful support of spontaneous CAVH in children with renal failure and too poor a blood flow to control azotemia. PMID- 3345244 TI - Hemodynamic changes during acetate dialysis, bicarbonate dialysis and hemofiltration. AB - Twenty uremic patients submitted to three different dialytic procedures (6 patients to acetate dialysis, 8 patients to bicarbonate dialysis, 6 patients to hemofiltration) were monitored in respect to the hemodynamic parameters recorded with a thermistor Swan-Ganz catheter. During acetate dialysis there was an increment of cardiac index (CI) up to positive values (+4.8%), while resistance index (RI) decreased progressively until it reached -16.5%. During bicarbonate dialysis CI, after an initial fall, remained constant and RI increased (+8.6%). During hemofiltration CI decreased constantly throughout the entire procedure while RI increased until +12.9%. We concluded that during diffusive transport the buffer used plays an important role in determining hemodynamic responses to fluid removal; during convective transport vascular resistance increases in spite of acetate. PMID- 3345245 TI - Invasiveness of enterobacteria related to the presence of high molecular weight plasmids. AB - A study of 41 strains of Shigella, Escherichia coli, and Salmonella was performed. The presence of high-molecular-weight plasmids, invasiveness in HEp-2 cells and the ability to produce a positive Sereny test were tested. Five of the seven strains of Salmonella typhimurium harboured a 62 Md plasmid and invaded HEp 2 cells. Two strains of S. typhimurium and a S. paratyphi-B strain lacked plasmids but were still invasive. Among the 27 strains of Shigella and enteroinvasive E. coli (EIEC) 25 strains harboured a high molecular weight plasmid. 27 of the Shigella/EIEC strains invaded HEp-2 cells and 25 produced a positive Sereny test. One strain of Shigella sonnei was invasive in HEp-2 cells and gave a positive Sereny test, but plasmids were not demonstrated. Of the eight non-enteropathogenic E. coli 5 strains harboured plasmids of 100 to 140 Md size; only one of the strains invaded HEp-2 cells; none of the strains produced a positive Sereny test. The study shows that tests for pathogenicity (Sereny test, HEp-2 cell test) are usually positive in the Shigella and EIEC group of bacteria; these bacteria also usually carry a high molecular weight plasmid. However, among non-enteropathogenic bacteria plasmids of 100 to 140 Md size can be observed without any correlation to invasive properties. Genetic information from gene loci located to plasmids and chromosomes is required to give a positive Sereny test. The presence of high molecular weight plasmids does not seem to be necessary for expression of in vitro invasiveness of S. typhimurium. PMID- 3345246 TI - Relationship between Mycobacterium avium, Mycobacterium paratuberculosis and "wood pigeon mycobacteria". Determinations by DNA-DNA hybridization. AB - The DNA-DNA homology percentages obtained in this study indicate that M. avium and M. paratuberculosis belong to one species. Consequently, M. paratuberculosis ought to be considered a variant of M. avium, and the following designations are proposed: Mycobacterium avium, subsp. avium. Mycobacterium avium, subsp. paratuberculosis. Identification and classification of "wood pigeon mycobacteria" occurring in wild animals have been problematic due to their dysgonic and mycobactin-dependent growth. DNA-DNA homology percentages indicate that these bacteria are closely related to reference strains both of M. avium and of M. paratuberculosis. "Wood pigeon mycobacteria" should therefore be classified as atypical strains of M. avium, and the following designation is proposed: Mycobacterium avium subsp. columbae. PMID- 3345247 TI - A rapid assay for protein-A in Staph. aureus strains, using immunomagnetic monosized polymer particles. AB - Monosized magnetic polystyrene beads, Dynabeads M-450, coated with sheep IgG were used in an agglutination test for the detection of cell-surface protein-A, based on Fc-protein-A binding. Ninety-three per cent of the bovine Staphylococcus aureus strains isolated from clinical mastitis expressed surface protein-A. The agglutination test was rapid compared to FITC-labelled IgG binding or dog-serum agar precipitation test for protein-A, and was significantly correlated with these methods. Scanning electron micrographs demonstrated binding of protein-A positive bacteria to the particle surface, thus bridging the beads and forming the agglutination lattice. The microsphere agglutination assay described is a quick, simple and reproducible method for detecting surface protein-A in staphylococci. PMID- 3345248 TI - Characterization of the dermal lesions induced by a purified protein from toxigenic Pasteurella multocida. AB - The dermonecrotic effect of purified Pasteurella multocida toxin (PMT) was studied sequentially in guinea pigs and rats. The skin reaction was initially an acute inflammatory reaction, with edema and emigration of neutrophils and a few eosinophils and diapedesis of some erythrocytes. Four hours after intracutaneous injection the vessels were congested and thrombocytes were focally attached to the endothelial wall. Twenty-four h after the injection the inflammatory reaction appeared more severe and venules and arterioles were thrombosed. Necrotic changes were seen in hair follicles and in striated muscle fibers. Crude extracts from P. multocida and Clostridium perfringens injected intracutaneously into guinea pigs induced skin lesions qualitatively similar to the lesions induced by the purified PMT, indicating that dermonecrotic bacterial toxins may share similar biochemical properties. PMID- 3345249 TI - The occurrence and significance of fibronectin in livers from chronic alcoholics. An immunohistochemical study of early alcoholic liver injury. AB - The occurrence and distribution of fibronectin (FN) was assessed by an immunoperoxidase technique in liver biopsies from alcoholics without and with acinar zone 3 fibrosis of varying degrees. Increased amounts of FN was found diffusely in zone 3 areas with a perisinusoidal and pericellular localization. FN was closely correlating to the pattern of fibrosis but increased amounts of FN could also be seen in biopsies without fibrosis as visualized in Picro-Sirius stained sections. There was no topographical relationship to liver cells with fatty changes, Mallory bodies or to alcoholic hepatitis. It is made probable that FN is of significance in the development of early liver fibrosis in alcoholics and that FN may act as a chemotactic factor for collagen producing cells and as a skeleton for the new collagen formation. PMID- 3345250 TI - Effect of oral N-acetylcysteine administration on human blood neutrophil and monocyte function. AB - N-acetylcysteine (NAC) is known to be a scavenger of free oxygen radicals, and recent in vitro studies have demonstrated that it is also able to inhibit leukocyte function. The clinical significance of these effects is, however, not known. In this study we have measured the effect on human blood neutrophil and monocyte function of a single 400 mg dose of NAC administered orally. Administration of NAC to ten healthy volunteers resulted in significant reduction of neutrophil chemiluminescence response following activation by opsonized zymosan as compared to four non-treated persons acting as controls. No effect was observed on the chemotaxis of either cell type or on monocyte chemiluminescence response. These findings suggest that NAC may be beneficial in clinical conditions like cystic fibrosis, where tissue damage may be a consequence of the effects of increased release of toxic oxygen radicals and proteolytic enzymes. PMID- 3345251 TI - Polycystic kidney disease. Morphological diagnosis of recessive and dominant polycystic kidney disease in infancy and childhood. AB - Histological findings in 75 children with polycystic kidney disease were analysed. The patients had been divided into recessive (RPKD), dominant (DPKD), and sporadic cases on the basis of family investigations. The histological findings in the patients with RPKD and DPKD were compared with each other in order to define criteria for classification of the sporadic patients. The kidneys of the neonatally-deceased patients with RPKD (26 patients) and DPKD (4 patients) were macroscopically very similar. On histological investigation, all patients with RPKD (32 patients) showed cysts derived from the collecting ducts. In DPKD, the cyst epithelium was more variable, and the presence of glomerular cysts served as a useful histological marker of this disorder. In RPKD there was diffuse biliary dysgenesis, in contrast to the normal liver in the neonatally deceased DPKD patients. However, one DPKD patient who survived also had biliary dysgenesis. Using the observed differences between RPKD and DPKD as criteria, all sporadic patients with satisfactory histological material could be classified as RPKD. We conclude that the differential diagnosis between RPKD and DPKD can be based on kidney and liver histology. PMID- 3345252 TI - Serum from diabetic patients enhances synthesis of arterial basement membrane like material in cultured smooth muscle cells. AB - The effect of serum from both type I and type II diabetic subjects on the metabolism of arterial basement membrane (BM)-like material was studied in cultures of rabbit aortic smooth muscle cells. The basement membrane-like material was isolated from the cell-layer by a combined sonication and centrifugation technique. Serum from type I diabetic persons added to the incubation medium increased statistically significantly the incorporation of L [4,5]-3H-leucine into the basement membrane-like material as compared to serum from non-diabetic subjects (2P less than 0.05). The same effect was seen with serum from type II diabetic patients as compared to serum from nondiabetic subjects (2P less than 0.05). No effect of serum from type I diabetic persons was seen in degradation experiments. Incubation medium supplemented with normal serum and extra glucose neither changed the production of basement membrane-like material nor the disappearance rate of radioactive leucine from the basement membrane-like material in degradation experiments. The present study indicates that serum from diabetic subjects enhances the production of arterial basement membrane-like material from arterial smooth muscle cells in culture. The obtained data may be relevant for the understanding of the development of macroangiopathy among diabetic patients. PMID- 3345253 TI - Campylobacter pylori is associated with chronic gastritis but not with active peptic ulcer disease. AB - Campylobacter pylori is supposed to be involved in the pathogenesis of gastroduodenal peptic ulcer diseases and chronic gastritis. In order to study whether the Campylobacter pylori in the stomach of peptic ulcer patients is related to ulcer itself or to a co-existing chronic gastritis, we examined the frequency of the bacteria in Giemsa stained histological sections of biopsy specimens from a series of patients with active peptic ulcer and from series of non-ulcer control subjects. We found no difference in the frequency of Campylobacter- positive cases between ulcer patients and non-ulcer controls when the comparison was done within the same category of chronic gastritis; e.g., within the category of chronic superficial gastritis 74% and 78% of cases showed the bacteria in antral biopsies from ulcer patients and from non-ulcer controls, respectively. In both ulcer patients and control subjects, in similar way in both antral and body mucosa, the Campylobacter pylori was strongly associated with chronic superficial gastritis but was more weakly associated with chronic atrophic gastritis, and the bacteria were only occasionally seen in normal mucosa. We conclude that Campylobacter pylori is associated with chronic gastritis in peptic ulcer patients but is not related to active ulcer. PMID- 3345254 TI - Human peritoneal macrophages. Production in vitro of the active terminal complement components C5 to C9 and a functional alternative pathway of complement. Brief report. AB - Endotoxin-stimulated human peritoneal macrophages were cultured in serum-free medium with agarose beads. Monospecific antibodies to human C3c, C3g, C5, C6, C7, C8, C9 and to C9-neoantigen bound to the beads. This shows that activated C3 and the terminal complement complex (TCC), made from complement components C5 to C9, were generated on the beads. De novo synthesis was confirmed by agarose binding of tritium-labelled protein. Moreover, C3-derivatives and C9-neoantigen were detected on normal serum-treated agarose beads but not on beads kept in factor B depleted or heat-inactivated sera, implying that an intact alternative complement pathway was required for our findings. The macrophages thus synthesize the active complement components of the alternative and terminal pathways in vitro. PMID- 3345255 TI - Influence of antihypertensive treatment on basal cerebral arteries in spontaneously hypertensive rats. A morphometric study. AB - Spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) were treated with a combination of a beta 1-blocker (metoprolol) and a calcium antagonist (felodipine) from 1 to 4 or from 4 to 6 months of age. Basal cerebral arteries were fixed by immersion and embedded in plastic. The ratio between media thickness and luminal radius was determined in cross-sectioned arteries for a standardized condition, assuming a smooth and circular internal elastic membrane. The treatment caused a significant decrease in blood pressure and a normalization of m/r ratios in basal cerebral arteries when initiated in young as well as in adult SHR and SHRSP, i.e. the therapy efficiently prevents as well as reverses hypertensive arterial changes. Even though 4-month-old treated rats were still significantly hypertensive, their m/r ratios did not differ from those of normotensive controls. The latter results may indicate that the treatment affects the vessel walls also through other mechanisms than by decreasing the pressure load. PMID- 3345256 TI - Benign nevus cells in the lymph nodes. An immunohistochemical study. AB - Aggregates of nevus cells in the axillary lymph nodes may give rise to a suspicion of metastatic breast cancer. Usually the nevus cells are confined to the capsule or the trabeculae, but in the present case, clusters of nevus cells were also observed in the peripheral sinus. Immunohistochemical analysis for S 100 protein and epithelial membrane antigen established the true nature of the cells. PMID- 3345257 TI - Peritoneal, benign, cystic mesothelioma with free-floating cysts, re-examined by new methods. A case report. AB - A histologically-confirmed, multicystic, benign mesothelioma, with free-floating, thin-walled cysts, in the abdominal cavity of a 27-year-old woman was reported in 1954. After removal of all visible cysts by laparotomy, the patient was healthy and well for 29 years, when she was surgically treated for cholecystitis and gall bladder stones in 1982. The whole peritoneum was found covered with small cysts lined by mesothelial cells. The patient is (April 1987) well, with no complaints. Sections from the old paraffin blocks were studied by means of scanning, transmission electron microscopy and immunohistochemistry. These methods confirmed the histological diagnosis. The authors discuss whether such a lesion really is a benign tumor or should rather be otherwise classified. PMID- 3345258 TI - Studies on clinical isolates of coagulase-negative staphylococci resistant to methicillin. Evidence of cross-resistance between methicillin and cephalothin. AB - The in vitro susceptibility to cephalothin and cefuroxime of 195 isolates of methicillin-resistant coagulase-negative staphylococci was determined by the agar diffusion test, using 7.5% NaCl-supplemented agar. The distribution of the inhibition zone diameters for isolates of S. epidermidis (S. biotype 1) as well as for S. haemolyticus (S. biotype 4) was trimodal. While 4% of the isolates were found susceptible to cefuroxime, 39% of the S. epidermidis/S. hominis (S. biotype 1) isolates and 34% of the S. haemolyticus (S. biotype 4) isolates were found susceptible to cephalothin by this method. Eight of these isolates (six S. epidermidis, two S. haemolyticus) were selected for susceptibility testing by the tube-dilution method, together with four isolates (three S. haemolyticus, one S. epidermidis) found resistant to cephalothin by the agar-diffusion test. The first mentioned isolates were all found susceptible to cephalothin with MICs less than or equal to 2 micrograms/l, while the last-named all were resistant with MICs greater than or equal to 16 micrograms/ml. Population analyses revealed sub populations of highly resistant bacteria in all methicillin-resistant isolates of S. epidermidis (S. biotype 1), as well as in all isolates of S. haemolyticus (S. biotype 4). We thus concluded that methicillin-resistance in isolates of coagulase-negative staphylococci implies resistance to cephalosporins and that the difference between S. epidermidis and S. haemolyticus as regards cephalosporin-susceptibility is quantitative and not qualitative. Eighty-nine per cent of the 195 methicillin-resistant isolates in this study were resistant to penicillin and at least one more antibiotic. We therefore think that resistance to penicillin and one or more non-beta-lactam antibiotics strongly suggests methicillin-resistance and that such isolates should be further tested on hypertonic media. PMID- 3345259 TI - Isolation of Campylobacter spp. and Yersinia enterocolitica from domestic animals and human patients in Kenya. AB - Rectal swabs or faecal samples from 992 domestic animals and 97 human patients in the Nairobi region were cultured for thermophilic Campylobacter species and Yersinia enterocolitica. The highest isolation rate of campylobacters was obtained from diarrhoeic pigs (55.1%), followed by healthy chicken (51.5%), diarrhoeic dogs (47.2%), healthy pigs (44.0%), healthy ducks (29.4%), healthy goats (6.3%), healthy cattle (5.8%), diarrhoeic humans (3.1%), and healthy sheep (2.0%). Only one strain of Y. enterocolitica was obtained. This isolate, which conformed to Nilehn's biotype 1, was recovered from one (0.7%) of the 150 healthy pigs examined. Out of 317 thermophilic campylobacters isolated, 163 (51.4%) were classified as C. jejuni, whereas 127 (40.1%) belonged to C. coli. The remaining 27 strains fell into three categories which did not conform to any defined species. Of the total number of isolates, 74.1% were resistant to metronidazole, 90.9% were resistant to triphenyltetrazolium chloride (TTC), and 50.2% reduced selenite. The results indicate that domestic animals may play a significant role in the epidemiology of human campylobacteriosis in the Nairobi region by serving as reservoirs. Y. enterocolitica seems to be rare among man and animals in this area. PMID- 3345260 TI - Clinical and histological intercorrelations in pigmented naevi indicating potential melanoma precursor lesions. AB - A series of 577 pigmented naevi from an equal number of patients has been studied histopathologically without access to clinical information. Later the histological findings have been compared with clinical information obtained by sending a questionnaire to the patients. The correlations between the many histological and clinical variables have been studied. Patients with a red or fair hair colour, a freckled, easily sunburnt skin type and/or a poor suntanning ability have the tendency to develop irregular and atypical naevi. Histological variables like nuclear atypia, mitoses, lymphocyte reaction, fibrosis and "shoulder"-phenomenon regarding the growth pattern of naevi are correlated to this delicate skin type. These findings support til theory that irregular and atypical naevi may be potential precursors to malignant melanomas as patients with this skin type belong to the melanoma risk group. PMID- 3345261 TI - Mesenterial-window hyperplasia in the lactating rat. AB - By examining the true mesentery adjacent to the small gut before and after weaning, as well as in age-matched controls, we found that the number of mesenteric windows, their total area, and their total DNA content increased significantly during lactation. Simultaneously, Feulgen-DNA absorption analysis in individual mesenteric cells showed that these had a normal DNA stemline, and a normal distribution within the G1-G2 range. The hyperplasia and growth developed and declined temporally somewhat parallel in the mesenterial windows and their adjacent small gut, suggesting that an as yet unknown common factor(s) governs the hyperplastic growth in both these tissues. The novel physiological, mesenterial-window hyperplasia in the lactating rat described in the present study may prove useful for studies of the mesenteric function and the regulation of cell proliferation. PMID- 3345263 TI - Studies on ampicillin resistance in Achromobacter xylosoxidans. Brief report. AB - Population analyses of susceptibility to ampicillin in ampicillin-susceptible and ampicillin-resistant strains of Achromobacter xylosoxidans revealed the existence of ampicillin-resistant subpopulations in ampicillin-susceptible isolates. Bacteria resistant to a concentration four times the one that inhibited the majority population had a frequency of 10(-3) to 10(-4). Strains isolated from aqueous environments are often found susceptible to ampicillin, while sporadic cases of infections with A. xylosoxidans are often caused by ampicillin-resistant strains. We suggest that the isolation from clinical specimens of ampicillin susceptible strains, therefore, may be an indication of nosocomial infections due to recently contaminated aqueous solutions or medical equipment. PMID- 3345264 TI - Hemisphere differences for components of mental rotation. AB - The hemispheric functional lateralization of components of mental rotation performance was investigated. Twenty right-handed males were presented with rotated alphanumerics and unfamiliar characters in the left or right visual field. Subjects decided if the laterally presented stimulus was identical to or a mirror image of a center standard stimulus. Reaction time and errors were measured. Previous mental rotation findings were replicated and the visual field variable produced significant effects for both dependent measures. An overall right visual field advantage was observed in the latency data, suggesting a left hemisphere superiority for at least one component process of the task. A significant interaction in the error data showed that alphanumerics produced less errors in the right visual field than in the left visual field, consistent with a left hemisphere superiority for processing verbal symbolic material. No such hemispheric difference in accuracy was found for unfamiliar characters. PMID- 3345262 TI - ELISA versus routine tests in the diagnosis of patients with systemic and neurobrucellosis. AB - Sera from patients in different stages of brucellosis as well as sera and cerebrospinal fluid (CSF) from patients with central nervous system (CNS) brucellosis and controls, were tested by ELISA for Brucella-specific IgG, IgM and IgA. The results were compared with culture findings, micro-agglutination (MA), slide agglutination with Rose Bengal (RB), and Brucella melitensis stained antigens (SA). In sera of patients with acute brucellosis (296), ELISA was positive for IgM (100%), IgG (97%) and IgA (98%), and comparable results were found in sera of patients with subacute brucellosis (44): IgG (100%), IgM (86%) and IgA (100%). However, in patients with chronic brucellosis (40), IgG and IgA were consistently positive (100%) while IgM was only positive in 33% of their sera. The MA and RB showed similar results, being more positive in patients with acute (98%) and subacute (84%) than in chronic (61%) brucellosis. The SA and culture showed significantly lower positive results. In the CSF of patients with CNS brucellosis (45), ELISA was positive in 100%, 20% and 85% for IgG, IgM and IgA, respectively, compared to 13% positive by culture, 25% by MA and 22% by RB. ELISA was negative in the CSF specimens from patients with brucellosis without CNS involvement (66), or meningitis other than Brucella (62), and no meningitis (144). Thus, ELISA with its IgG, IgM and IgA profiles is the test of choice in the diagnosis of patients with brucellosis, especially those with chronic or CNS infection. PMID- 3345266 TI - Characteristics of recovery of drawing ability in left and right brain-damaged patients. AB - Drawings of a "person" were obtained from 21 patients with left brain damage (LBD) and 13 patients with right brain damage (RBD) at hospital discharge and 1 month postdischarge, corresponding to 2-4 and 6-8 weeks postonset, respectively. Early LBD drawings were simplistic and often incoherent. Most were placed in the upper left quadrant of the page. RBD drawings were scattered, fragmented, and elaborately detailed. Many showed evidence of left-sided neglect. The resolution of drawing disability also differed between the two groups: LBD subjects recovered drawing abilities more rapidly and more completely than RBD subjects. These differences in drawing characteristics and in the resolution of drawing disability were discernable for experienced neuropsychologists. PMID- 3345265 TI - Separate brain potential characteristics in children with reading disability and attention deficit disorder: color and letter relevance effects. AB - This experiment was on event-related potential (ERP) indicants of the selective neural processing of black vs. white and letter vs. nonletter stimuli in boys (8 12 years of age) with and without a reading disability (RD) and/or attentional deficit disorder (ADD). Selective neural processing was measured by the increase or difference in ERP amplitude in response to stimuli that were relevant as compared to irrelevant to the color or letter attention task. The 52 children that participated in the study constituted four groups: 25 normal reading children (17 without ADD and 8 with ADD), and 27 RD children (11 without ADD and 16 with ADD). ERPs were recorded over the left and right occipital, central, and frontal regions. Selective neural processing due to stimulus relevance was reduced in boys with RD as compared to normal readers. This reduced selectivity was indicated by a predominantly symmetrical reduction in the magnitude of a positive difference potential over the central regions, between 300 and 360 msec, and then by a left greater than right hemisphere reduction in the magnitude of a positive difference potential over the occipital regions, at about 400 msec. Task relevance increased the within-subject and condition variability of this occipital positive component and this effect was greater for boys without than with RD, particularly over the left hemisphere. Selective neural processing due to stimulus relevance was greater in boys with ADD as compared to those without ADD. This was indicated by an increase in the magnitude of a positive difference potential between 320 and 400 msec over the central and frontal regions and a slow, late, negative difference potential between 600 and 800 msec over the central and occipital regions. These ADD effects tended to be greater over the right than left hemisphere. The unique polarity, scalp distribution, and time course of the effects of RD as compared to ADD on ERPs to relevant stimuli clearly indicated these two disorders, in part, involve different underlying brain deficits. PMID- 3345267 TI - Rate of forgetting in mild Alzheimer's-type dementia. AB - Patients with mild dementia of the Alzheimer's type (DAT) and matched controls were examined for rate of forgetting line drawings of common objects. DAT patients demonstrated rapid forgetting in the first 10 min after learning to criterion. This finding is discussed with respect to memory consolidation and neuropathologic changes in dementia of the Alzheimer's type. PMID- 3345268 TI - Processing from LVF, RVF and BILATERAL presentations: examinations of metacontrol and interhemispheric interaction. AB - Observers indicated whether two successively presented drawings of faces were identical or differed in one feature (hair, eyes, mouth, jaw). The first face of each pair was presented at the fixation point and the second was presented to the left visual field-right hemisphere (LVF-RH), right visual field-left hemisphere (RVF-LH), or to both visual fields simultaneously (BILATERAL). On DIFFERENT trials the RT of correct responses depended on which feature differed and the pattern of feature location effects was significantly different on LVF-RH and RVF LH trials. On BILATERAL trials the feature location effect was identical to that obtained on RVF-LH trials and significantly different from that obtained on LVF RH trials. In addition, the percentage of errors and RT of correct responses were both higher on BILATERAL trials than on unilateral trials. Implications of these results are considered for the concept of "metacontrol" in neurologically normal humans and for models of interhemispheric interaction. PMID- 3345269 TI - Separate brain potential characteristics in children with reading disability and attention deficit disorder: relevance-independent effects. AB - The effects of reading disability (RD) and attention deficit disorder (ADD) on event-related potentials (ERPs) were investigated in 52 boys between 8 and 12 years of age. There were four groups: 25 children without RD divided into two groups (17 without ADD and 8 with ADD) and 27 children with RD divided into two groups (11 without ADD and 16 with ADD). The children participated in three tasks ("games") designed to assess selective attention to the color black (vs white), to any of two letters (vs. two patterns), and to any of 12 letters (vs. 12 patterns). ERPs were recorded over the left and right occipital, central, and frontal hemispheres. Children with RD as compared to those without RD were characterized by the following ERPs: (1) a smaller amplitude positive wave at about 240 msec (P240) over the left central hemisphere: (2) a smaller amplitude positive wave at about 500 msec (P500) over the right central hemisphere: (3) a larger P500 over the right central hemisphere: (3) a larger P500 over both left and right occipital hemispheres: and (4) smaller within-subject-and-condition variability of ERP waveform. These effects did not differ significantly for the three games and, therefore, were not specific to letter processing per se. The effects of RD did not interact with the effects of ADD for the most part. The ERPs clearly indicated these two disorders, in part, involve different underlying brain processes. PMID- 3345271 TI - The risk of adverse reactions in anaesthesia. PMID- 3345270 TI - The effect of stroke on object recognition. AB - Stroke patients were tested for their ability to recognize familiar objects shown in photographs, and we have confirmed previous reports that damage to the right hemisphere impairs recognition of objects shown at an "unusual angle". Additionally, these patients were impaired in matching unfamiliar (nonsense) objects which had been rotated. These impairments are discussed in the context of key task demands, particularly the need to extract depth cues from the photographs, and to rotate form elements to determine whether the samples provided different views of the same object. In the context of other work, these results suggest impairment of advanced perceptual skills which are needed to establish relationships of and among features of the forms. PMID- 3345272 TI - Plasma glutathione S-transferase concentration as a measure of hepatocellular integrity following a single general anaesthetic with halothane, enflurane or isoflurane. AB - The plasma concentration of hepatic glutathione S-transferase (GST) was measured in matched groups of patients who received halothane, enflurane or isoflurane anaesthesia for elective minor surgery. The GST concentrations increased significantly at 3 h after anaesthesia in patients who received halothane or enflurane, but not in patients who were given isoflurane. A secondary increase in GST concentration, at 24 h, was seen in a small number of individuals who received halothane or enflurane. Abnormal GST concentrations were found in 50% of patients following halothane anaesthesia, 20% following enflurane and 11% after isoflurane. The small but significant increases in GST concentrations in patients receiving halothane or enflurane suggests an impairment of hepatocellular integrity following the administration of these anaesthetics. In contrast, isoflurane anaesthesia did not appear to be associated with this effect. PMID- 3345273 TI - Plasma prilocaine concentrations after three techniques of brachial plexus blockade. AB - Brachial plexus blockade (n = 30: 10 axillary, 10 perivascular subclavian, 10 interscalene) was performed on 28 patients, using 35 ml of 1.5% prilocaine in plain solution. Plasma prilocaine concentrations were measured at intervals over the following 60 min. There was no significant difference in the prilocaine concentrations between the three groups. One asymptomatic patient in the interscalene group had a peak prilocaine concentration greater than the accepted threshold for toxic symptoms. PMID- 3345274 TI - Lack of correlation between the anaesthetic and anti-convulsant potencies of althesin, ketamine and methohexitone. AB - Using Sprague-Dawley rats, the anti-convulsant potencies of Althesin, ketamine and methohexitone were determined for bicuculline-and strychnine-induced seizures and compared with their effects on hyperbaric seizures. All three anaesthetics protected against both types of chemical convulsants; the degree of protection varied from 34 to 151%, with Althesin being the most effective. However, there was no correlation between their anti-convulsant and anaesthetic potencies, and no relationship between the effects on chemical convulsions and the interactions of the same agents with hyperbaric convulsions. These data suggest that the order of anti-convulsant potencies at equivalent anaesthetic concentration is Althesin much greater than ketamine = methohexitone, and that neither bicuculline-nor strychnine-induced seizures are a good model for hyperbaric convulsions. PMID- 3345275 TI - Effect of suxamethonium on the ICP of cats with and without thiopentone pretreatment. AB - Twelve cats were assigned equally to two groups, one with normal, and the other with artificially-increased intracranial pressure. When suxamethonium was administered to these animals, the intracranial pressure increased in both groups, irrespective of their baseline intracranial pressure. When the same dose of suxamethonium was administered after pretreatment with thiopentone in both groups of animals, the intracranial pressure again increased from the control values. PMID- 3345276 TI - Rate of induction of hypotension with trimetaphan modifies the intracranial pressure response in cats. AB - An infusion of 0.1% trimetaphan was administered to eight cats with artificially increased intracranial pressure (ICP) in order to decrease their mean arterial pressure (MAP) from 121 +/- 9.5 (SEM) to 58 +/- 4.6 mm Hg in less than 1 min. All cats developed an increase in intracranial pressure (ICP) (from 16 +/- 1.4 to 23 +/- 3.2 mm Hg) accompanied by a partial rebound in MAP. Eight additional cats received 0.1% trimetaphan to decrease their MAP from 128 +/- 13.4 to 52 +/- 8.1 mm Hg over more than 2 min. Four of these cats followed the same pattern, with ICP increases from 19 +/- 1.1 to 31 +/- 3.9 mm Hg, while in the other four ICP did not change. In nine of the 12 cats with an ICP increase, that increase was initiated before the partial MAP rebound. We conclude that trimetaphan causes clinically significant ICP increases in cats with increased ICP, that partial rebound in MAP frequently exacerbates these increases in ICP, and that rapid induction of hypotension tends to increase the frequency with which trimetaphan increases ICP. PMID- 3345277 TI - Anterior fontanelle pressure responses to tracheal intubation in the awake and anaesthetized infant. AB - In order to define the changes in intracranial pressure which occur during tracheal intubation in young infants, a Ladd transducer was used to monitor anterior fontanelle pressure (AFP) non-invasively in awake (group 1, n = 14) and anaesthetized (group 2, n = 10) infants during intubation of the trachea. Heart rate and systolic arterial pressure were also recorded. In quiet, undisturbed infants, AFP (mean +/- SEM) was similar in groups 1 (9.6 +/- 0.5 mm Hg) and 2 (8.7 +/- 0.8 mm Hg); with crying, AFP increased significantly in both groups. During laryngoscopy in group 1, AFP increased to 33.5 +/- 3.6 mm Hg, which was significantly greater than in the quiet infant, but did not differ significantly from measurements in the crying infant. In group 2, AFP increased significantly to 15.8 +/- 18 mm Hg during laryngoscopy. This increase was significantly less than the group 1 response. Neither heart rate nor systolic arterial pressure changed significantly in either group during laryngoscopy--when compared with measurements in the quiet state. It was concluded that AFP increases significantly during intubation and during crying in the infant. The response to intubation is only partially attenuated by the prior administration of general anaesthesia. PMID- 3345278 TI - Comparison of atracurium-induced neuromuscular blockade in neonates, infants and children. AB - The potency of atracurium was determined in neonates, infants and children during thiopentone-fentanyl-nitrous oxide in oxygen anaesthesia using single dose response curves. The effective doses producing 50% depression of the first twitch of the train-of-four were significantly lower in neonates and infants than in children (82 and 112 v. 135 micrograms kg-1). Following a standard dose of atracurium 0.5 mg kg-1, 95% depression of the first twitch occurred more rapidly in neonates than in children (0.9 v. 1.4 min), while recovery to 10% of the control twitch height occurred more rapidly in neonates than in the other two groups (22.7 v. 29.7 and 28.6 min). It is concluded that neonates and infants require less atracurium to produce a given degree of neuromuscular blockade compared with older children. However, prompt recovery can be expected in all healthy paediatric patients following a standard intubating dose of atracurium 0.5 mg kg-1. PMID- 3345279 TI - Effect of adrenaline on extradural anaesthesia and plasma bupivacaine concentrations during caesarean section. AB - The effect of adrenaline on the efficacy of extradural block and plasma bupivacaine concentrations was investigated in women undergoing elective (n = 40) and emergency (n = 40) Caesarean section. Patients were randomly allocated within these two groups to receive 0.5% bupivacaine 20 ml either plain or with adrenaline 1 in 200,000, as a single fractionated extradural injection. The elective plain group needed significantly more supplementary analgesia compared with the other three groups (P less than 0.05). In the elective group, plasma bupivacaine concentrations were significantly lower in the subgroup receiving extradural adrenaline than in the plain subgroup. This effect was not observed when comparing only those who received bupivacaine 100 mg. In the emergency group, there were no significant differences in plasma bupivacaine concentrations between the plain and adrenaline subgroups. Maximum plasma concentrations correlated significantly (P less than 0.0001) with dose of bupivacaine (mg kg-1). It is concluded that extradural adrenaline does not usefully reduce systemic absorption of 0.5% bupivacaine, but may improve its efficacy in extradural anaesthesia for elective Caesarean section. PMID- 3345280 TI - Spinal anaesthesia with hyperbaric bupivacaine. Effects of age on neural blockade and pharmacokinetics. AB - Effects of ageing were studied on the neural blockade and the pharmacokinetics after subarachnoid administration of 0.5% bupivacaine 3 ml in 8% glucose in two groups of 15 male patients, between 20 and 55 yr and older than 55 yr, respectively. The blockade was performed with the patient in the sitting position. Two minutes after the injection the patient was placed in the supine position. The time to maximum cephalad spread and the upper level of analgesia increased with advancing age, whereas the time to onset of motor blockade decreased with advancing age. Effects of age on the total duration of analgesia and motor blockade could not be demonstrated. Age had no effect on the peak plasma concentration of bupivacaine. The time to peak concentration and the terminal half-life increased, whereas the total plasma clearance decreased with advancing age. PMID- 3345281 TI - Influence of pretreatment with a monoamine oxidase inhibitor (phenelzine) on the effects of buprenorphine and pethidine in the conscious rabbit. AB - The existence of a severe toxic interaction (occasionally fatal) from the clinical use of pethidine and monoamine oxidase (MAO) inhibitors is well established. The present study evaluates the possibility of such an interaction existing for the opioid partial agonist buprenorphine. Conscious rabbits (n = 6 in each group) pretreated 18-24 h previously with physiological saline or the MAO inhibitor phenelzine 20 mg kg-1 s.c. were subsequently given physiological saline, pethidine 5 mg kg-1 i.v. or buprenorphine 0.1 or 1.0 mg kg-1 i.v. Whilst saline was without effect and phenelzine produced only a small increase in the rabbit temperature, the combination of phenelzine and pethidine produced a marked, prolonged hyperpyrexia (+4.4 +/- 0.19 degrees C; P less than 0.001), hypertension (+33.9 +/- 3.1 mm Hg; P less than 0.01) and agitation. Three rabbits died, at 35, 45 and 55 min after the pethidine-phenelzine combination. Buprenorphine was without significant effect on any parameter when given after phenelzine. In the model used buprenorphine, in contrast to pethidine, showed no interaction with the MAO inhibitor phenelzine. PMID- 3345282 TI - Anaesthetic experience--the view from below. AB - The anaesthetic experience gained during general professional training is reviewed, indicating the spectrum of patients managed and training received. The experience gained was broadly in line with the guidelines recommended by the Faculty of Anaesthetists. The advantage of movement between hospitals at a junior level is noted, as is the value of a case record book, for both the individual and the Anaesthetic Department. PMID- 3345284 TI - An unusual complication. PMID- 3345283 TI - Additional blood-gas variables for the rational control of oxygen therapy. PMID- 3345285 TI - Routine use of atropine in obstetric anaesthesia. PMID- 3345286 TI - Atracurium for ECT in plasma cholinesterase deficiency. PMID- 3345287 TI - A new congenital dyserythropoietic anaemia. AB - A new dominantly inherited dyserythropoietic anaemia is described. In the bone marrow, many of the nonspecific morphological characteristics described in congenital dyserythropoietic anaemias were seen; however, dysmorphic cells were rare. The acidified serum test was positive with one out of 17 sera tested; the negative sera included two that had haemolysed HEMPAS erythrocytes in the acid Ham test. Anti-i-agglutination was negative. No aberrations of red cell membrane protein glycosylation were observed. Serum cholesterol was low. Bilirubin conjugation was deficient but icterus was resolved by treatment with phenobarbital. PMID- 3345288 TI - Red cell aggregation during normal pregnancy. AB - Red cell aggregation (RCA) is responsible for the increase in whole blood viscosity at lower shear rates. RCA depends on the concentrations of red cells and plasma proteins with a high molecular weight and a large and asymmetrical spatial structure such as fibrinogen, immunoglobulin M and alpha 2-macroglobulin. During normal pregnancy, changes occur in all these concentrations. In a prospective study these changes and their influence on the resulting RCA were investigated in 24 healthy women with normal pregnancies. RCA was determined by light reflection measurement (syllectometry). RCA considerably increased during normal pregnancy in spite of the physiological haemodilution. The aggregation half time, used as a measure for RCA, decreased from an average non-pregnant value of 5.6 s to 3.3 s at 37 weeks. Multiple regression analysis showed that the increase in RCA could be mainly attributed to the raised fibrinogen concentration. However, at 37 weeks other factors, in addition to fibrinogen, contribute significantly to the increase in RCA. PMID- 3345289 TI - Biochemical studies on McLeod phenotype red cells and isolation of Kx antigen. AB - Red cells of the McLeod blood group phenotype have weak Kell antigens, lack Kx antigen and have acanthocytic morphology. We have immunoprecipitated Kell antigens from McLeod red cells and show that they are markers on the same 93 kDa membrane protein that carries Kell antigens on normal red cells. However, as determined by Western immunoblotting, McLeod red cells have a marked deficiency of this protein. We have also studied the near-neighbour relationship of McLeod and common Kell red-cell membrane proteins by cross-linking intrinsic sulphydryl groups by oxidation, catalysed with orthophenanthroline and copper, or by cross linking amino groups with dimethyl-3,3'-dithiobispropionimidate. Results were analysed by diagonal mapping in two-dimensional gels. No abnormalities of membrane protein inter-relationship were detected in McLeod red cells. We have isolated Kx antigen from K0 red cells by immunoprecipitation with human alloimmune anti-Kx serum, isolation of immune complexes from detergent solubilized cell membranes with protein A-Sepharose and analysis of the eluted immune complex by SDS-PAGE under reducing conditions. Kx antigen is a marker on a red-cell membrane protein of approximately 37 kDa. Ko (Knull) red cells have about twice the amount of Kx antigen as do red cells of common Kell type. McLeod red cells have no detectable Kx antigen by serological tests or by immunoprecipitation. PMID- 3345290 TI - Cyclosporin A in adult-onset cyclic neutropenia. PMID- 3345292 TI - Hairy cell leukemia and occupational exposures. PMID- 3345291 TI - Antilymphocyte globulin for myelodysplastic syndrome. PMID- 3345293 TI - Possible association of disseminated intravascular coagulation (DIC) with the chromosomal region 17q12-21 and the gene for glycoprotein IIb-IIIa complex. PMID- 3345294 TI - Lack of evidence for the presence of neutrophil autoantibodies in the serum of patients with Felty's syndrome. AB - Sera of 22 patients with Felty's syndrome and 14 patients with rheumatoid arthritis were tested in assays routinely used for the detection of neutrophil antibodies (i.e. immunofluorescence, agglutination and cytotoxicity tests) as well as in the antibody-dependent lymphocyte-mediated granulocytotoxicity test. One or more of the routinely used assays were positive in a high percentage of the sera (77% and 64%, respectively). The antibody-dependent lymphocyte-mediated granulocytotoxicity test was only positive with sera of three patients with Felty's syndrome. Positive results in the immunofluorescence and agglutination tests could be attributed to the presence of immune complexes in the sera, whereas positive antibody-dependent lymphocyte-mediated granulocytotoxicity tests were probably due to the presence of HLA alloantibodies. It is concluded that serological tests routinely used for the detection of neutrophil autoantibodies should be interpreted with caution in patients with Felty's syndrome. Our results also indicate that the neutropenia in Felty's syndrome is rarely, if ever, due to neutrophil-specific autoantibodies. PMID- 3345295 TI - Complement inhibitor S protein is associated with membranes of red blood cells from patients with paroxysmal nocturnal haemoglobinuria. AB - S protein is a plasma glycoprotein (Mr = 78,000) which binds to nascent C5b-7 complexes upon complement activation in the fluid phase in whole serum. It thereby protects innocent bystander cells from complement mediated lysis. It is unknown whether S protein also functions as complement inhibitor on cell surfaces. We here report that S protein is recognized on red blood cells (RBC) from patients with paroxysmal nocturnal haemoglobinuria (PNH), but not on normal RBC. RBC from eight PNH patients showed 12-48% haemolysis subsequent to complement activation in the fluid phase, while normal RBC did not respond. Preincubation of the PNH cells with affinity-purified antibodies against human S protein resulted in a three- to five-fold increase of haemolysis, while preincubation of these cells with S protein decreased haemolysis by 40%. In contrast, haemolysis remained unaffected by other unrelated antibodies, i.e. IgG anti-Rh(D) and anti-A. If PNH RBC, normal RBC pretreated with 2-amino ethylisouronium bromide (AET), or untreated normal RBC, respectively, were incubated with purified S protein in vitro, the uptake of antibodies against S protein was significantly enhanced with PNH and with AET-treated, but not with untreated normal RBC. Additionally, while normal RBC did not respond to reactive lysis initiated by purified C5b-6 and C7, PNH as well as AET-RBC showed significant haemolysis that could be inhibited by S protein in a dose-dependent fashion. These findings strengthen the assumption that the increased sensitivity of PNH cells towards reactive complement lysis is either due to the lack of an inhibitor of the terminal complement sequence and/or enhanced insertion of the membrane attack complex. These defects of PNH RBC may partly be overcome by the fluid phase complement inhibitor S protein which binds to PNH RBC and may thereby suppress homologous cytolysis. PMID- 3345296 TI - Heterogeneous defects of platelet secretion and responses to weak agonists in patients with bleeding disorders. AB - Eleven patients with mild bleeding disorders had as a common abnormality, impaired platelet aggregation and secretion with low concentrations (0.5-1.0 micrograms/ml) of collagen and, in most cases, an absence of second phase aggregation with epinephrine. Platelet granule contents were normal, ruling out storage pool deficiency. To characterize further the platelet abnormalities, we measured aggregation, 14C-5HT secretion, and TxB2 formation induced by a variety of platelet agonists. In eight of the 11 patients we observed decreased initial rates as well as extents of aggregation with one or more weak agonists (ADP, epinephrine, thromboxane A2 and the endoperoxide analogue U44069), i.e. agonists which induced secretion only as a result of aggregation, but normal responses to strong agonists such as arachidonate and high (10 micrograms/ml) concentrations of collagen, which can induce secretion in the presence or absence of aggregation. In all of these patients, TxB2 formation with arachidonate and all concentrations of collagen was normal. The platelet defects in these eight patients have been designated as weak agonist response defects (WARDs). In contrast, the initial aggregation responses to all weak agonists were normal in the three other patients, while secretion and TxB2 formation induced by strong agonists were impaired. Thus, in contrast to the eight patients above, the platelet defects in these three patients were characteristic of defects in the secretion response per se. The results obtained in the 11 patients studied indicate that these types of platelet disorders, previously referred to as primary secretion defects, include defects in the initial platelet responses which precede secretion (WARD) as well as defects in the secretory mechanism per se. Both groups of defects appear to be heterogeneous in nature. PMID- 3345297 TI - Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). I. Characterization and preliminary evaluation in plasma. AB - Monoclonal antibodies (mabs) were raised against X-oligomers, the earliest soluble fragments released from crosslinked fibrin (XL-FN), by the action of plasmin. Two of the mabs (NIBn 52 and NIBn 123) were monospecific for X-oligomers in that they showed no binding to fibrinogen, the plasmic fragments of fibrinogen (D and E) and non-crosslinked fibrin (X, Y, D and E), or the terminal digestion product of XL-FN, fragment DD-E. One other mab (NIBn 178) was panspecific for X oligomers in that it exhibited a weak affinity for fibrinogen. The mabs were used to develop a two-site immunoradiometric assay (IRMA) and an enzyme-linked immunospecific assay (ELISA) which permitted the specific measurement of X oligomers directly in plasma, rather than in serum. This immunoassay is a true assay of fibrinolysis as distinct from fibrinogenolysis and may be a potential aid in the diagnosis and evaluation of thrombosis. In preliminary studies, the assay detected low levels of X-oligomers in normal plasma and elevated levels in patients with disseminated intravascular coagulation. PMID- 3345298 TI - Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). II. Evaluation in a variety of clinical conditions. AB - Plasmas from patients with a wide variety of thrombotic and presumed prethrombotic conditions were examined for high molecular weight crosslinked fibrin degradation products (known as X-oligomers) using a two-site enzyme-linked immunospecific assay (ELISA). This assay employed a catcher-tag principle using two monoclonal antibodies (mabs) directed towards different epitopes on the complex X-oligomer fraction. In general, thrombotic events (pulmonary embolism, PE, myocardial infarction, MI, peripheral vascular disease, PVD, and disseminated intravascular coagulation, DIC) were accompanied by elevated levels of X oligomers in the plasma. During pregnancy the value of X-oligomer assays was demonstrated to be a clear-cut marker for pre-eclampsia. Patients following a variety of forms of surgery present with heterogeneous plasma levels of X oligomers and this may merely reflect the formation and lysis of the fibrin formed during and after surgery. The possible value of this ELISA procedure in monitoring thrombolytic therapy is discussed with a critical analysis of the data presented herein. While the assay of X-oligomer was demonstrated to be a valuable marker of fibrinolysis in plasma, more extensive data are required in order to assess whether such an assay is of diagnostic value in thrombosis-related conditions. PMID- 3345299 TI - An acquired Bernard-Soulier-like platelet defect associated with juvenile myelodysplastic syndrome. AB - Bernard-Soulier syndrome is an inherited bleeding abnormality characterized by thrombocytopenia with large platelets and deficiency of the platelet membrane glycoprotein (GP) Ib-IX complex. We have identified a young female with an acquired Bernard-Soulier-like platelet defect and a coexisting primary myelodysplastic disorder. Abnormal bruising had developed at age 5. A normal platelet count with some giant platelets was noted at age 7. At age 9 she developed a large haematoma following surgery. Laboratory investigation revealed thrombocytopenia and large platelets. Platelet membrane glycoprotein analysis showed a marked deficiency of the components of the GP Ib-IX complex (approximately equal to 25% of normal). Flow cytometry revealed two populations of platelets: a predominant population of large platelets lacking the GP Ib-IX complex and a minor population of normal-sized platelets with normal GP Ib-IX expression. The patient developed progressive anaemia, more severe thrombocytopenia and neutropenia, and circulating blast cells were seen. A bone marrow showed gross hypercellularity with marked dysplasia of all three lineages and increased blasts. Marrow cytogenetic studies showed the presence of monosomy 7 in all metaphases, with an additional trisomy 21 in 10%. Peripheral blood cells were normal 46XX. The above data are consistent with an acquired myelodysplastic syndrome associated with a Bernard-Soulier-like platelet defect. PMID- 3345301 TI - Determination of leucine metabolism and protein turnover in sheep, using gas liquid chromatography-mass spectrometry. AB - 1. Whole-body protein synthetic rates in non-pregnant ewes were determined by the continuous infusion of L-[15N]- and [1-13C]leucine and measuring the plasma enrichment of leucine, alpha-ketoisocaproate (alpha-KIC) and expired carbon dioxide by gas-liquid chromatography-mass spectrometry. 2. The mean whole-body protein synthesis estimated from plasma leucine flux corrected for oxidation was 5.38 (SE 0.54) g/kg per d. 3. Under the conditions of the present study leucine oxidation was 0.323 (SE 0.067) mmol/kg per d and accounted for 10.71 (SE 2.26) % of plasma [13C]leucine flux. Deamination of leucine was 0.55 (SE 0.035) mmol/kg per d and accounted for approximately 17% of plasma [15N]leucine flux. 4. The rate of alpha-KIC reamination to leucine, calculated by subtracting 13C flux from 15N flux, was 0.228 (SE 0.101) mmol/kg per d. 5. The rate of whole-body protein degradation was 4.49 (SE 0.54) g/kg per d and there was a net protein gain of 0.89 (SE 0.21) g/kg per d. PMID- 3345302 TI - Heat production and growth costs in the young rat. PMID- 3345300 TI - Selenium (selenate) transport by human placental brush border membrane vesicles. AB - 1. Selenate uptake by human placental brush-border-membrane vesicles was studied in order to establish whether this anion shares a pathway with sulphate. 2. Selenate uptake was found to be saturable with respect to medium selenate and was inhibited by the anion exchange inhibitor 4,4'-diisothiocyano-stilbene-2,2' disulphonate (DIDS). 3. Anions which have a similar tetrahedral shape to selenate, e.g. chromate, molybdate, tungstate and sulphate, were effective inhibitors of selenate uptake when added to the incubation medium. 4. Sulphate inhibited selenate influx in a dose-dependent fashion; moreover sulphate was found to be a competitive inhibitor of selenate uptake. 5. It is concluded that selenate and sulphate share a pathway for transport in the human placental microvillus membrane. PMID- 3345303 TI - Effect of cooking, pH and polyphenol level on carbohydrate composition and nutritional quality of a sorghum (Sorghum bicolor (L.) Moench) food, ugali. AB - 1. The present work was undertaken to study the effects of cooking, pH and polyphenol level on carbohydrate composition and nutritional quality of sorghum (Sorghum bicolor (L.) Moench). Three different sorghum varieties; Dabar, Feterita and Argentine containing zero, intermediate to low and high levels of polyphenols respectively were used in the study. From these varieties uncooked, uncooked acidified, cooked, and cooked acidified diets were prepared. Diets were characterized with regard to resistant starch (RS), dietary fibre (DF), acid detergent fibre (ADF) and amino acid content. Raw materials were further analysed for content and composition of non-starch polysaccharides and Klason lignin. The nutritional properties were studied in balance trials with rats. True protein digestibility (TD), biological value (BV), net protein utilization, digestible amino acids, digestible energy (DE) and digestible DF were used as criteria in the nutritional study. 2. Cooking at neutral and acid pH resulted in significantly higher assayed values for DF. Increase in DF could be accounted for by formation of RS. Approximately 50% of RS was recovered in the faeces. 3. In vitro values for protein associated with ADF and in vivo balance values using rats suggest that an endosperm protein fraction, kafirins, was made unavailable during cooking. This resulted in reduced TD and increased BV. It is assumed that unavailable kafirins serve as a nitrogen source for microflora in the hind-gut. 4. Dietary polyphenols changed the excretory route for N from urine to faeces. This resulted in lower TD and higher BV in Argentine (high in polyphenols) than in Dabar and Feterita (low in polyphenols), although dietary lysine (first limiting amino acid) was the same in the three varieties. 5. Variation in DE of the diets was attributed to DF, RS and the amount of faecal protein, which in turn were influenced by undigested kafirins and polyphenols. PMID- 3345304 TI - The effect of Gypsophila saponins in the diet on mineral status and plasma cholesterol concentration in the rat. AB - 1. Immature, male Wistar rats were allocated to one of six groups and caged individually. The first group was given a semi-synthetic diet containing 38 mg iron and 55 mg zinc/kg (basal group). The second and third groups were given a diet containing 10 mg Zn and 12 mg Fe/kg respectively (low-Zn and low-Fe groups). Groups four, five and six were given similar diets containing 20 g Gypsophila saponins/kg. After 21 d the Fe and Zn status of the rats was estimated and plasma cholesterol concentration determined. 2. Measurements of whole blood haemoglobin concentration, packed cell volume and liver Fe stores indicated that rats in the basal + saponin and low-Fe + saponin groups had a significantly reduced Fe status when compared with their controls. Rats in the low-Zn + saponin group also showed a trend toward reduced Fe stores. 3. Zn status, as judged by femur Zn concentration, was not adversely affected by the inclusion of Gypsophila saponins in the diet. 4. Consumption of the saponins resulted in a significant reduction in blood cholesterol concentration, with rats in both the low-Fe groups having significantly lower concentrations than their basal and low-Zn counterparts. 5. In view of suggestions that the consumption of saponins should be encouraged because of their ability to lower blood cholesterol, possible effects on Fe metabolism should be investigated further, particularly with respect to the levels and sources of saponin in the human diet. PMID- 3345305 TI - The influence of a high-protein, low-carbohydrate diet on bone development in the fetuses of rat dams with streptozotocin-induced diabetes. AB - 1. The purpose of the present study was to determine the effects of diet on the mandibles and growth centres of the long bones in the fetuses of diabetic rat dams given a normal diet compared with those given a high-protein, low carbohydrate diet. 2. On the 9th day of gestation, the controls, groups 1 and 3, were injected with citrate buffer and given 200 and 600 g protein/kg diets respectively. Groups 2 and 4 were injected with 40 mg streptozotocin/kg body weight and pair-fed with groups 1 and 3 respectively on the 200 and 600 g protein/kg diets. 3. On day 22, some dams were injected with either 45Ca or [14C]proline. Mandibles and long bones were removed and weighed and analysed for Ca content, 45Ca uptake, collagen and collagen synthesis. 4. The body-weights, and mandibular and long-bone weights of the fetuses in the diabetic 200 g protein/kg group were smaller than those of the non-diabetic 200 g protein/kg group, whereas those of the diabetic 600 g protein/kg group showed no difference from the non-diabetic 600 g protein/kg group. 5. The rate of collagen synthesis was higher in the fetuses of the diabetic 600 g protein/kg group than those of the non-diabetic group. Bones of the diabetic 200 g protein/kg group were lower in collagen content when compared with the non-diabetic group, whereas there was no difference between the diabetic and non-diabetic 600 g protein/kg groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345306 TI - Factors affecting the voluntary intake of food by sheep. 4. The effect of additives representing the primary tastes on sham intakes by oesophageal fistulated sheep. AB - 1. Sheep with oesophageal fistulas were sham-fed on pelleted lucerne (Medicago sativa) hay to assess the palatability of added chemicals representing the tastes of sweet (sucrose), sour (hydrochloric acid), salt (sodium chloride), bitter (urea) and umami (monosodium glutamate; MSG). 2. Plain pellets and four concentrations of each chemical were sham-fed for 30 min after 5.5 h deprivation in 5 x 5 Latin-square experiments following a period of adaptation feeding. 3. Sucrose, at concentrations of 15-120 g/kg air-dried pellets, depressed intakes with a linear relation between intake (I; g) and concentration (C; g/kg): I = 1001-3.42C. 4. HCl at 6.25-25.0 g/kg pellets had no effect on sham intakes but at 50 g/kg reduced them by 50% of control (P less than 0.05). 5. NaCl at 50 200 g/kg increased sham intakes by 26% (P less than 0.01) with no evidence of a dose related effect. 6. Urea at 10-80 g/kg decreased sham intakes by 26.9% (P less than 0.01) with no evidence of a dose-related effect. 7. MSG at 5-40 g/kg in two experiments increased sham intakes by 16.1 and 40.8% (P less than 0.05). In another experiment at 1-8 g/kg there was no significant effect. 8. When palatability and post-ingestive effects are separated by sham-feeding, the effect of added chemicals on intake may be completely different from when they are ingested normally (e.g. NaCl and sucrose). This newly developed technique enables the palatability effect of feed additives to be tested critically and economically. PMID- 3345307 TI - Haematological and tissue abnormalities in chicks caused by acute and subclinical folate deficiency. AB - 1. Haematological, histological and ultrastructural findings in young chicks fed on a purified diet severely deficient in folate are reported. 2. Growth of the birds was greatly depressed and they had a macrocytic anaemia. Other haematological changes included abnormal nuclear formations in erythrocytes, numerous mitoses and hypersegmented granulocytes. 3. Megaloblasts were observed in bone marrow and their fine structure is described for the first time in an avian species. 4. Morphological changes occurred also in the liver. The parenchyma had damaged sinusoidal endothelium, inflammatory cells and no glycogen. Mitochondria were damaged and many were associated with unusual crystalline structures. 5. Chickens fed on a semi-purified diet of low folate content showed no growth depression or clinical signs of deficiency but had abnormal haematological values and morphological changes that resembled those seen in birds fed on the purified diet. 6. These abnormalities responded to dietary supplements of pteroylmonoglutamic acid in a dose-related manner and may be useful in diagnosing subclinical folate deficiency. PMID- 3345308 TI - Messenger RNA levels of plasma proteins following fasting. AB - 1. The effect of fasting on hepatic mRNA levels of seven plasma proteins was examined in the rat. 2. The levels of mRNA were measured directly in cytoplasmic extracts by hybridization to specific 32P-labelled cDNA probes. 3. Following a 48 h period of fasting, the mRNA levels of apolipoprotein E, apolipoprotein A-IV, albumin, transferrin, and transthyretin decreased by 15-30%, while apolipoprotein A-II decreased by 78% compared with non-fasted control rats. The mRNA for apolipoprotein A-I increased by 33%. 4. These findings suggest that mRNA levels in the liver following fasting are regulated independently and variations in these levels may be due to differences in transcription rates or mRNA stability. PMID- 3345310 TI - Studies in sheep on the absorption of magnesium from a low molecular weight fraction of the reticulo-rumen contents. AB - 1. Six sheep, three animals per diet, were prepared with rumen fistulas and fed on frozen grass or grass-maize pellets to give magnesium intakes of 1.79 and 2.23 g/d respectively. The mean apparent availabilities of Mg in sheep fed on frozen grass and grass-maize pellets were 0.31 and 0.36 respectively. 2. The rumen contents were fractionated by straining the digesta through linen cloth and then differentially centrifuged to give 20,000 g and 100,000 g supernatant fractions. 3. In all sheep, regardless of diet, at 4 and 16 h after a meal, 50 and 60% respectively of the total Mg in the rumen contents was found in strained rumen fluid while 30 and 38% respectively of the total Mg was found in the 100,000 g supernatant fraction. 4. The net absorption of Mg from the temporarily isolated and washed reticulo-rumen was studied using either 100,000 g supernatant fractions of rumen contents from sheep fed on one or other of the two diets, or inorganic buffers containing the same concentration of Mg and other macroelements. 5. The Mg was readily absorbed from the 100,000 g supernatant fraction placed in the rumen with the rate of absorption being 7.3 mumol/l per min (505 mg/d) from the supernatant fraction obtained from sheep fed on frozen grass and 11.3 mumol/l per min (781 mg/d) from the supernatant fraction from sheep fed on grass-maize pellets. In the same sheep, the previously described rates of Mg absorption from the 100,000 g supernatant fraction were similar to those obtained from the comparable inorganic buffers. 6. The effects of varying concentrations of potassium and sodium on the net absorption rate of Mg (as 24Mg) and on the one-way efflux of Mg (as 28Mg) from supernatant fractions or rumen fluid and inorganic buffers were investigated using the temporarily-isolated and washed rumen in three sheep. Although the net absorption rate of 24Mg from supernatant fractions or buffers containing similar K concentrations varied significantly between sheep, a similar percentage decrease in the absorption rates of both 24Mg and 28Mg was found for each sheep as the K concentration was increased. 7. One pair of sheep was fed on the frozen grass and the other pair was fed on the grass-maize pellets. Their daily intakes of K were then increased to 50 g/d for 14 d by intrarumen infusion of potassium chloride. In three of the four sheep the plasma Mg concentration fell within 12 h of the start of the KCl administration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3345309 TI - Influence of lactose on phosphate metabolism in rats. AB - 1. Lactose, sucrose or maltose were administered to rats by gavage together with 32PO4, and blood 32P was determined. 2. PO4 uptake into blood was increased only when lactose and PO4 were administered into the gut. 3. Weaned male rats were fed on a control diet or a diet containing 30, 60 or 120 g lactose/kg. After a 5 d period of adaptation, a 6 d P balance was carried out. After a further 24 d blood levels of PO4, and calcium and PO4 uptake by brush-border membrane vesicles prepared from the renal cortex, were determined. 4. The absorption and retention of P were higher in lactose-fed rats. Faecal P excretion decreased with increasing dietary lactose content. Urinary P excretion was lower in the rats fed on 30 and 60 g lactose/kg whereas the 120 g lactose/kg diet increased urinary P. 5. Membrane vesicles isolated from rats fed on the diets containing 30 and 60 g lactose/kg showed a higher uptake of PO4, but with the 120 g lactose/kg diet uptake was lower than with membrane vesicles isolated from rats fed on the control diet. 6. A statistically significant increase in the serum PO4 level was observed in the rats fed on the diet with 120 g lactose/kg. 7. The presence of lactose in the diet caused a stimulatory effect on PO4 absorption and retention. PMID- 3345311 TI - Effects of dietary conditions on the pool sizes of precursors of phosphatidylcholine and phosphatidylethanolamine synthesis in rat liver. AB - We developed a new method for the determination of choline- and ethanolamine containing precursors of phosphatidylcholine and phosphatidylethanolamine after their separation by HPLC and we have studied the effects of different dietary conditions on the pool sizes of these metabolites in rat liver. Fasting for 48 h induced only a small decrease in the amounts of phosphatidylethanolamine and its water-soluble precursors. Upon refeeding with a high-sucrose, fat-free diet for 72 h, the levels of ethanolamine-containing compounds were only slowly restored. The effects of various dietary conditions on the amounts of phosphatidylcholine and its water-soluble precursors were much more pronounced. Fasting induced a sharp decrease, especially of the amount of cholinephosphate. However, the levels of phosphatidylcholine and the choline-containing precursors were rapidly restored upon refeeding for 24 h. Continued refeeding for an additional 48 h enhanced the cholinephosphate pool size to a level more than double that found in normally fed rats. The latter effect was accompanied by an inhibition of the enzyme CTP:choline-phosphate cytidylyltransferase. The results are discussed in view of a possible regulatory mechanism that may balance the amounts of phosphatidylcholine and phosphatidylethanolamine. PMID- 3345312 TI - Intestinal very-low-density lipoprotein secretion in the genetically obese Zucker rat. AB - The objectives of this study were to measure intestinal very-low-density lipoprotein (VLDL) production in obese Zucker rats and to assess an eventual effect of a high-fat diet. VLDL secretion was specifically inhibited by orotic acid, and intestinal VLDL output was measured following the Triton WR-1339 method. After a control diet, total VLDL secretion (without orotic acid) was 4.8 +/- 0.3 and 1.4 +/- 0.1 mg triacylglycerol/ml in obese and lean rats, respectively, decreasing by 30% in obese rats after fat-feeding. Intestinal VLDL production was similar in obese and lean rats fed the control diet (0.32 +/- 0.05 and 0.27 +/- 0.05 mg triacylglycerol/ml, respectively), increasing 2.5-fold after fat-feeding in both genotypes. Thus, intestine contributed 21 and 60% of total VLDL in lean but only 7 and 24% in obese rats with the control and high-fat diets, respectively. These results show that the intestine of obese Zucker rats does not contribute to their hypertriglyceridemia, suggesting that it originates solely from liver. Moreover, their intestinal VLDL production was stimulated by fat-feeding to the same extent as in lean animals. PMID- 3345313 TI - Metabolism of ether glycolipids with potentially antineoplastic activity by Ehrlich ascites tumor cells. AB - Ehrlich ascites tumor cells were incubated in vitro with rac-1-O-[1' 14C]octadecyl-2-O-methylglycero-3-beta-D-glucopyranosi de for 24 h. The potentially antineoplastic ether glycolipid was rapidly metabolized by the cells to radioactive 1-O-octadecyl-2-O-methylglycerol (70 pmol/10(6) cells per h) and further acylated to 1-O-octadecyl-2-O-methyl-3-acylglycerols. Incubation of Ehrlich ascites cells with synthetic rac-1-O-[1'-14C]octadecyl-2-O-methyl-3 palmitoylglycerol showed that this metabolite is reconverted by deacylation to 14C-labeled 1-O-octadecyl-2-O-methylglycerol. The latter compound or a metabolite derived therefrom may be the 'toxic principle' of both the ether glyceroglycolipids and ether glycerophospholipids having a 1-O-alkyl-2-O methylglyceryl moiety, as suggested by Unger et al. (J. Natl. Cancer Inst. 78 (1987) 219-222). PMID- 3345314 TI - An ATP-dependent system specific for degradation of long-lived proteins in permeabilized cells. AB - We have characterized a digitonin-permeabilized cell system for the ATP-dependent degradation of endogenous long-lived proteins. Proteolysis requires Mg2+ and ATP hydrolysis. Other nucleotide triphosphates (CTP, UTP) can partially replace the ATP requirement. The enhanced rate of degradation of long-lived proteins in response to serum starvation is maintained in the permeabilized cell system and can be partially inhibited by lysosomal inhibitors. The maintenance of intracellular architecture and ease of manipulation of soluble components make the permeabilized cell system ideal for studying the proteolysis of both endogenous and exogenous substrates. PMID- 3345315 TI - Chemotaxis of fibroblasts toward nonapeptide of elastin. AB - Bovine ligamentum fibroblasts, which produce elastin, migrate towards a positive chemical gradient of human platelet-derived growth factor and of the tropoelastin repeat hexapeptide Val-Gly-Val-Ala-Pro-Gly, as previously shown. They are also responsive to two permutations of a nonapeptide that repeats in tropoelastin, i.e., Ala-Gly-Val-Pro-Gly-Phe-Gly-Val-Gly and Gly-Phe-Gly-Val-Gly-Ala-Gly-Val Pro. Concentration curves and checkerboard assays prove that the nonapeptides are chemoattractants. The component pentapeptide, Gly-Phe-Gly-Val-Gly, is chemotactic, while the component tetrapeptide Ala-Gly-Val-Pro is not. The hexapeptide competitively suppresses the nonapeptide chemotaxis suggesting the involvement of a common cell receptor. The results support the concept that elastin has multiple cell recognition sites as measured by the chemotactic response and that among the hydrophobic repeating sequences of elastin chemotacticity is selectively and multiply localized. PMID- 3345316 TI - Toxins from the venom of the green mamba Dendroaspis angusticeps that inhibit the binding of quinuclidinyl benzilate to muscarinic acetylcholine receptors. AB - Two protein toxins that displace the muscarinic antagonist quinuclidinyl benzilate from rat cortex synaptosomal membranes have been isolated from the green mamba (Dendroaspis angusticeps) venom by gel filtration on sephadex G-50, chromatography on the ion-exchangers Bio-Rex 70 and Sulphopropyl-Sephadex C-25 and reversed-phase HPLC. Toxin 1 has 64 amino acids and four disulfides and a formula weight of 7200 and the corresponding values for toxin 2 are 63, 4 and 6840, respectively. Ultracentrifugation gave a molecular weight of 6900 for toxin 1 and 6700 for toxin 2, Quinuclidinyl benzilate that binds to all types of muscarinic cholinergic receptor was displaced to about 50% by both toxins. This partial displacement indicates that the toxins might be specific for one subtype of receptor. PMID- 3345317 TI - The neuronal basis of the anesthetic state: a comparative physiological approach. II. The influence of anesthetics on various reactions in flies. AB - The sensitivity of specific neuronal pathways to Halothane and N2O has been investigated in flies. The effects were tested by monitoring the responses of photoreceptors and their second order neurons, as well as two behavioral responses--a leg reflex induced by light flashes and head movements induced by moving optical patterns--chosen because their neuronal substrates are fairly well known. Sensitivity to both agents rises with the length of dendrites and the number of input synapses of the neurons involved. The findings confirms the hypothesis, formulated in Part I of this paper, that neurons with long dendrites and/or axonal endings and large numbers of input synapses are the elements in the central nervous system with the highest sensitivity to anesthetic action. Under physiological conditions this kind of neuron is capable of "gain-control": the relationship between input and output is modified according to functional requirements. Possible molecular mechanisms leading to functional impairment under anesthesia are discussed. PMID- 3345318 TI - Ambivalence in modelling oblique saccades. AB - Human oblique saccades might be made by synchronized but independent vertical and horizontal pulse generators; we call this the Cartesian theory. Another hypothesis is that the oblique amplitude and angle are coded centrally and trigonometrically-derived signals are sent to the horizontal and vertical muscles (the polar coordinate theory). We took a Cartesian model and cross-coupled the two generators to produce saccades identical to those of a polar coordinate model. This is disproof by counter-example: the experimental evidence claimed to support the polar coordinate model does not necessarily do so. Moreover, the behavior reported for oblique saccades is so variable, contradictory, idiosyncratic, and species-dependent that any model of the central organization of oblique saccades is probably premature. PMID- 3345321 TI - On the stability of the Travelling Salesman Problem algorithm of Hopfield and Tank. AB - The application of the method of Hopfield and Tank to the Travelling Salesman Problem (1985) has been re-examined in an effort to find a procedure for scaling to system sizes of real interest. As this failed, methods were tried to improve the algorithm, recognizing the importance of a "silicon implementation". No satisfactory refinement was found, and the reasons for algorithm failure have been identified. PMID- 3345319 TI - A theory for the use of visual orientation information which exploits the columnar structure of striate cortex. AB - A neural model is constructed based on the structure of a visual orientation hypercolumn in mammalian striate cortex. It is then assumed that the perceived orientation of visual contours is determined by the pattern of neuronal activity across orientation columns. Using statistical estimation theory, limits on the precision of orientation estimation and discrimination are calculated. These limits are functions of single unit response properties such as orientation tuning width, response amplitude and response variability, as well as the degree of organization in the neural network. It is shown that a network of modest size, consisting of broadly orientation selective units, can reliably discriminate orientation with a precision equivalent to human performance. Of the various network parameters, the discrimination threshold depends most critically on the number of cells in the hypercolumn. The form of the dependence on cell number correctly predicts the results of psychophysical studies of orientation discrimination. The model system's performance is also consistent with psychophysical data in two situations in which human performance is not optimal. First, interference with orientation discrimination occurs when multiple stimuli activate cells in the same hypercolumn. Second, systematic errors in the estimation of orientation can occur when a stimulus is composed of intersecting lines. The results demonstrate that it is possible to relate neural activity to visual performance by an examination of the pattern of activity across orientation columns. This provides support for the hypothesis that perceived orientation is determined by the distributed pattern of neural activity. The results also encourage the view that limits on visual discrimination are determined by the responses of many neurons rather than the sensitivity of individual cells. PMID- 3345320 TI - Physiology based simulation model of triangle shape recognition. AB - The present paper considers the relation between the shape of a triangle and probability of its recognition. An effect of triangle size on perception of its shape is examined in the first experiment. In the second the loci of eye fixations during triangle recognition task are recorded and analysed. A simulation model of the recognition process is proposed. The model is based on two main assumptions: 1. an accuracy of shape processing is related to the cortical magnification factor, 2. a subject's response depends on actual position of eye fixation. The validity of the model is verified by comparing the theoretical and experimental response distributions. Some psycho-physiological implications are then discussed. PMID- 3345322 TI - Privatization. PMID- 3345323 TI - Alcohol detoxification and withdrawal seizures: clinical support for a kindling hypothesis. AB - There has been speculation that a kindling model may have applicability to alcohol withdrawal syndromes and seizures, suggesting that repeated alcohol withdrawals may lead to increased severity of subsequent withdrawals. We evaluated historical and clinical variables of a group of male alcoholics with (n = 25) and without (n = 25) alcohol withdrawal seizures. We found that the number of detoxifications appeared to be an important variable in the predisposition to withdrawal seizures. The withdrawal seizure group had 12 of 25 (48%) patients with 5 or more previous detoxifications, compared to only 3 of 25 (12%) of the control group. A relationship between alcohol use history and withdrawal seizures was not supported by the data. These findings support the concept that previous alcohol withdrawals may "kindle" more serious subsequent withdrawal symptomatology, ultimately culminating in withdrawal seizures. PMID- 3345324 TI - Partial complex status epilepticus associated with cocaine abuse. PMID- 3345325 TI - Leukoencephalopathy in patients diagnosed as major depressive. PMID- 3345326 TI - 24-hour motor activity in genetically nervous and normal pointer dogs. PMID- 3345327 TI - Pre- and postdexamethasone cortisol and prolactin levels in sexual dysfunction and normal controls. PMID- 3345328 TI - Thyroid hormones during sleep deprivation. PMID- 3345329 TI - Biophysical aspects of microsphere engulfment by human neutrophils. AB - A quantitative investigation into the mechanism of neutrophil phagocytosis of opsonized microspheres possessing well defined dimensions was undertaken. Three aspects were documented: membrane conservation, cell adhesion to the spheres, and active cell cytoplasmic projection around the microspheres. The physical act of internalizing a particle by a cell involves a reduction in its plasma membrane area and an increase in its volume. As a consequence, a cell can internalize only a finite number of particles. A store of membrane area exists on cytoplasmic granules and may be recruited during phagocytosis. Previous measurements of neutrophil membrane area and volume served as a basis for estimates of the maximum number of internalized microspheres. A comparison with experimental prediction based on membrane conservation and degranulation agrees within 10% for a range of microsphere diameters, from 0.5 to 8 microns. This suggests that the limitation for additional particle uptake in the population of engorged neutrophils is the lack of excess plasma membrane area. In a random population of neutrophils, there was a sub-group, approximately 40%, which could no longer phagocytose before depleting their membrane stores. Several aspects of the engulfment process were investigated to elucidate the cause of this phagocytosis deficiency. It could be shown by single cell observation that these cases were associated with a lack of pseudopod projection, although adhesion was still evident between the cell membrane and the microspheres. PMID- 3345331 TI - 19F-nuclear magnetic resonance: measurements of [O2] and pH in biological systems. AB - 19F-nuclear magnetic resonance (NMR) has been used to determine both intracellular pH and oxygen concentrations in cell suspensions. Oxygen concentrations in Paracoccus denitrificans and insulinoma cells, RINm5F, in the NMR probe can be monitored directly by 1/T1 measurements of perfluorotripropylamine (FTPA)/lecithin emulsion added to the suspensions. With FTPA oxygen monitoring, we investigated the relative aeration capabilities of two types of NMR chambers. Both normal and transformed eucaryotic cells can be maintained in either chamber for at least 1-2 h at cytocrits of up to 20-25%, with 30% oxygen saturation and cell viabilities of 90-95%. Similar concentrations of procaryotes were maintained aerobic with high FTPA concentrations in the more efficient of the two NMR chambers. A new precursor molecule for the 19F-NMR pH indicator difluoromethylalanine, the para-chlorophenyl ester, has been tested and used in RINm5F cells and P. denitrificans, neither of which hydrolyzes methyl esters. PMID- 3345330 TI - Chromophore/protein and chromophore/anion interactions in halorhodopsin. AB - Halorhodopsin (HR), the light-driven chloride transport pigment of Halobacterium halobium, was bleached and reconstituted with retinal analogues with the pi electron system interrupted at different locations (dihydroretinals). The absorption maxima of the artificial pigments formed with the dihydroretinals are found to be very similar to those of the corresponding pigments formed by reconstitution of bacteriorhodopsin (BR) and sensory rhodopsin (SR). This strongly suggests that the distribution of charges around the retinal is similar in all three bacterial rhodopsins. Comparison of the primary, and proposed secondary, structures for HR and BR reveal conserved asparagine (asp) and arginine (arg) residues, which are likely candidates for the ionizable amino acids that interact with the retinal. In a second set of experiments absorption shifts due to the binding of anions to Sites I and II in HR, reconstituted with different retinal analogues, were used to estimate the locations of these binding sites relative to the retinal. Site I is localized near the Schiff base, and Site II near the ionone ring. On the basis of these results a structural model for HR is proposed, which accounts for the spectroscopic properties of HR in terms of the three buried arg residues and two of the buried asp residues in the protein. PMID- 3345332 TI - Membrane interactions in nerve myelin. I. Determination of surface charge from effects of pH and ionic strength on period. AB - We have used x-ray diffraction to study the interactions between myelin membranes in the sciatic nerve (PNS) and optic nerve (CNS) as a function of pH (2-10) and ionic strength (0-0.18). The period of myelin was found to change in a systematic manner with pH and ionic strength. PNS periods ranged from 165 to 250 A or more, while CNS periods ranged from 150 to 230 A. The native periods were observed only near physiological ionic strength at neutral or alkaline pH. The smallest periods were observed in the pH range 2.5-4 for PNS myelin and pH 2.5-5 for CNS myelin. The minimum period was also observed for PNS myelin after prolonged incubation in distilled water. At pH 4, within these acidic pH ranges, myelin period increased slightly with ionic strength; however, above these ranges, the period increased with pH and decreased with ionic strength. Electron density profiles calculated at different pH and ionic strength showed that the major structural alteration underlying the changes in period was in the width of the aqueous space at the extracellular apposition of membranes; the width of the cytoplasmic space was virtually constant. Assuming that the equilibrium myelin periods are determined by a balance of nonspecific forces/i.e., the electrostatic repulsion force and the van der Walls attractive force, as well as the short-range repulsion force (hydration force, or steric stabilization), then values in the period-dependency curve can be used to define the isoelectric pH and exclusion length of the membrane. The exclusion length, which is related to the minimum period at isoelectric pH, was used to calculate the electrostatic repulsion force given the other forces. The electrostatic repulsion was then used to calculate the surface potential, which in turn was used to calculate the surface charge density (at different pH and ionic strength). We found the negative surface charge increases with pH at constant ionic strength and with ionic strength at constant pH. We suggest that the former is due to deprotonation of the ionizable groups on the surface while the latter is due to ion binding. Interpretation of our data in terms of the chemical composition of myelin is given in the accompanying paper (Inouye and Kirschner, 1988). We also calculated the total potential energy functions for the different equilibrium periods and found that the energy minima became shallower and broader with increasing membrane separation. Finally, it was difficult to account directly for certain structural transitions from a balance of nonspecific forces. Such transitions included the abrupt appearance of the native period at alkaline pH and physiological ionic strength and the discontinuous compaction after prolonged treatment in distilled water. Possibly, in PNS myelin conformational modification of PO glycoprotein occurs under these conditions. The invariance of the cytoplasmic space suggests the presence of specific short-range interactions between surfaces at this apposition. PMID- 3345333 TI - Membrane interactions in nerve myelin: II. Determination of surface charge from biochemical data. AB - In our accompanying paper (Inouye and Kirschner, 1988) we calculated the surface charge density at the extracellular surfaces in peripheral and central nervous system (PNS; CNS) myelins from observations on the dependency of the width of the extracellular space on pH and ionic strength. Here, we have determined the surface charge density of the membrane surfaces in myelin from its chemical composition and the localization of some of its molecular components. We then analyzed the attractive and repulsive forces between the apposed surfaces and calculated equilibrium periods for comparison with the measured values. The biochemical model accounts for the observed isoelectric range of the myelin period and, with the surface charge reduced (possibly by divalent cation binding or a space charge approximation), the model also accounts for the dependency of period on pH above the isoelectric range. At the extracellular (and cytoplasmic) surfaces the contribution of lipid (with pI approximately 2) to the net surface charge is about the same in both PNS and CNS myelin, whereas the contribution of protein depends on which ones are exposed at the two surfaces. The protein conformation and localization modulate the surface charge of the lipid, resulting in positively-charged cytoplasmic surfaces (pI approximately 9) and negatively charged extracellular surfaces (pI approximately 2-4). The net negative charge at the extracellular surface is due in CNS myelin to lipid, and in PNS myelin to both lipid and (PO) glycoprotein. The net positive charge at the cytoplasmic surface is due in CNS myelin mostly to basic protein, and in PNS myelin to PO glycoprotein and basic protein. The invariance of the cytoplasmic packing may be due to specific short-range interactions. Our models demonstrate how the particular myelin proteins and their localization and conformation can account for the differences in inter-membrane interactions in CNS and PNS myelins. PMID- 3345334 TI - Analysis of the factors that influence the C=N stretching frequency of polyene Schiff bases. Implications for bacteriorhodopsin and rhodopsin. AB - In this study quantum mechanical calculations of force constants and normal mode analysis are used to elucidate the factors that influence the C=C and C=N stretching frequencies in polyenes and in protonated Schiff bases. The C=N stretching frequency is found to depend on both the C=N stretching force constant and the C=N-H bending force constant. Due to the contributions of these two modes, the C=N stretching frequency is particularly sensitive to the magnitude of the Schiff base counterion interactions and to the hydrogen bonding environment of the Schiff base nitrogen. Models for chromophore-protein interactions in the retinal binding site and for the photochemical transformations of bacteriorhodopsin and rhodopsin are evaluated in light of these results. PMID- 3345335 TI - Periaxonal K+ regulation in the small squid Alloteuthis. Studies on isolated and in situ axons. AB - A novel giant axon preparation from the squid Alloteuthis is described. Properties of in situ and isolated axons are similar. Periaxonal K+ accumulation is a function of the physiological state of the animal and of the axon and its sheathing layers. Carefully dissected isolated axons, and axons in situ in a healthy mantle, show much less K+ accumulation than previously reported in squid. It is suggested that the Schwann cells are involved in the observed K+ regulation. PMID- 3345336 TI - K+ accumulation in the space between giant axon and Schwann cell in the squid Alloteuthis. Effects of changes in osmolarity. AB - In a train of impulses in squid giant axon, accumulation of extracellular potassium causes successive afterhyperpolarizations to be progressively less negative. In Loligo, Frankenhaeuser and Hodgkin had satisfactorily accounted for the characteristics of this effect with a model in which the axon is surrounded by a space, width theta, and a barrier of permeability P. In axons isolated from Alloteuthis, we found that the model fitted the observations quite well. Superfusing the axon with hypotonic artificial seawater (ASW) caused theta and P to decrease, and, conversely, hypertonic ASW caused them to increase: this would be the case if both the space and the pathway through the barrier were extracellular. In some cases, in normal ASW, the afterhyperpolarizations in a train decreased very little, less than 0.7 mV. In these extreme cases, theta was estimated to be 190 nm and P to be 7 x 10(-4) cm s-1, both several times the values of 30 nm and 6 x 10(-5) cm s-1 estimated by Frankenhaeuser and Hodgkin. We suggest that in vivo the periaxonal space may be considerably wider than that seen in conventionally fixed squid tissue. PMID- 3345337 TI - The localization of a platelet GpIIb-IIIa-related protein in endothelial cell adhesion structures. AB - Previous studies have shown that human endothelial cells (ECs) adhere to fibrinogen (fg) and fibronectin (fn) and organize their cytoskeleton on these substrata. However, the mechanism governing this chain of events is poorly known. In ECs glycoproteins immunologically and biochemically similar to the platelet membrane GpIIb-IIIa complex have been described. The functional role of this complex in ECs remains to be established. In this study we show that the antigens recognized by polyclonal antibodies raised against human platelet GpIIb-IIIa and crossreacting with the EC form have a discrete and well-organized distribution at cell adhesion structures. Indeed these antigens are located at vinculin-rich focal contacts found at the membrane insertion of microfilament bundles of the stress fiber type. They are also found at cell-to-cell contacts and, with a diffuse pattern, at the dorsal surface of ECs. GpIIb-IIIa antibodies, added to EC suspensions prior to plating, inhibit EC spreading on fg and vitronectin (vn) substrata in a concentration-dependent way. In contrast, the antibodies are very poorly active when the cells are seeded on fn-coated glass. The same antibodies, added to adherent cells, disrupt cell-to-cell contacts and cause their rounding and detachment. Overall these results indicate that EC GpIIb-IIIa complex is involved in controlling the adhesion mechanism of these cells to extracellular matrix proteins. PMID- 3345338 TI - Changes in numbers and types of mast cell colony-forming cells in the peritoneal cavity of mice after injection of distilled water: evidence that mast cells suppress differentiation of bone marrow-derived precursors. AB - Two different types of cells in the peritoneal cavity of mice produce mast cell colonies in methylcellulose. "Large" mast cell colonies are produced by bone marrow-derived precursors resembling lymphoid cells by light microscopy (L-CFU Mast), whereas "medium" and "small" mast cell colonies are produced by morphologically identifiable mast cells (M-CFU-Mast and S-CFU-Mast, respectively). In the present study we eradicated peritoneal mast cells by intraperitoneal (IP) injection of distilled water. The regeneration process was investigated to clarify the relationship between L-CFU-Mast, M-CFU-Mast, and S CFU-Mast. After injection of distilled water, M-CFU-Mast and S-CFU-Mast disappeared, but L-CFU-Mast increased, and then M-CFU-Mast and S-CFU-Mast appeared, suggesting the presence of a hierarchic relationship. When purified peritoneal mast cells were injected two days after the water injection, the L-CFU Mast did not increase. In the peritoneal cavity of WBB6F1-+/+ mice that had been lethally irradiated and rescued by bone marrow cells of C57BL/6-bgJ/bgJ (beige, Chediak-Higashi syndrome) mice, L-CFU-Mast were of bgJ/bgJ type, but M-CFU-Mast and S-CFU-Mast were of +/+ type. The injection of distilled water to the radiation chimeras resulted in the development of bgJ/bgJ-type M-CFU-Mast and then S-CFU-Mast. The presence of mast cells appeared to suppress the recruitment of L-CFU-Mast from the bloodstream and to inhibit the differentiation of L-CFU Mast to M-CFU-Mast. PMID- 3345339 TI - Is there a role for selective vasodilation in the management of sickle cell disease? AB - To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted. PMID- 3345341 TI - Heme arginate: effects on hemostasis. AB - Hematin, the drug used for acute porphyric attacks, has been shown to cause disturbances in hemostasis, mainly because of its degradation products. Lately a new heme compound, heme arginate, has been developed for the treatment of porphyrias. In experimental animal studies as well as in clinical use it has proved to be well tolerated. To find out whether heme arginate has any effects on hemostasis we have studied a number of parameters of coagulation and fibrinolysis after a heme arginate infusion in seven healthy volunteers. All parameters studied remained practically unchanged except the coagulation factor X, which showed a transient, insignificant decrease during the maximal heme concentration. We believe that the lack of side effects is due to a better stability of heme arginate, the degradation rates being 1% for heme arginate and 61% for hematin in four hours. Our data favor the use of heme arginate in acute porphyrias as well as in other deficiency states of heme. PMID- 3345340 TI - Fibrinogen Birmingham: a heterozygous dysfibrinogenemia (A alpha 16 Arg----His) containing heterodimeric molecules. AB - Fibrinogen was isolated from the plasma of a 25-year-old female with a history of mild bleeding and several recent moderate to severe hemorrhagic episodes. Coagulability with thrombin approached 100% and varied directly with the time of incubation with the enzyme. High-performance liquid chromatography analysis of thrombin-induced fibrinopeptide release demonstrated retarded fibrinopeptide A (FPA) and fibrinopeptide B (FPB) release and the presence of an abnormal A peptide (FPA) amounting to 50% of the total. The same biochemical abnormalities were found in her asymptomatic father. Amino acid analysis and carboxypeptidase digestion of FPA demonstrated the substitution of His for Arg at A alpha 16. In contrast to the thrombin- and reptilase-sensitive Arg-Gly bond in the normal A alpha chain, the abnormal A alpha chain (A alpha) sequence is resistant to reptilase attack but is slowly cleaved by thrombin. To evaluate whether Birmingham A alpha and A alpha chains had been assembled nonselectively into heterodimeric (ie, 50% A alpha, A alpha) and homodimeric (ie, 25% A alpha, A alpha; 25% A alpha, A alpha) species, the clot and the clot liquor resulting from reptilase treatment of normal or Birmingham fibrinogen were separated, and each was then further incubated with thrombin to release remaining fibrinopeptides. Assuming that fibrinogen Birmingham contained heterodimeric molecules and that these and the normal molecules were completely incorporated into a reptilase clot, the expected coagulability would be 75%. In addition, subsequent thrombin treatment of the reptilase clot would release 50% of the total FPA and 75% of the total FPB present in the original sample. On the other hand, if only homodimeric fibrinogen species (50% A alpha, A alpha; 50% A alpha, A alpha) existed, the maximum reptilase coagulability would be 50%, and after thrombin treatment, 50% of the total FPB and no FPA would be recovered from the reptilase clot. We found the propositus's fibrinogen to be 68% coagulable, and we recovered 45% of the FPA and 70% of the FPB from the reptilase clot. Essentially the same coagulability and distribution of fibrinopeptides was found in the reptilase clot from her father's fibrinogen. We therefore conclude that fibrinogen Birmingham contains heterodimeric species (A alpha, A alpha) amounting to approximately 50% of the circulating fibrinogen molecules. The existence of heterodimers is consistent with a nonselective intracellular process of constituent chain assembly of dimeric plasma fibrinogen molecules. PMID- 3345342 TI - Evidence for tissue factor-dependent activation of the classic extrinsic coagulation mechanism in blood obtained from bleeding time wounds. AB - The activation of platelets and the coagulation mechanism was studied by collecting blood from a standard bleeding time incision at 30-second intervals and measuring the plasma concentrations of fibrinopeptide A (FPA), platelet factor 4 (PF4), and thromboxane B2 (TxB2). FPA was observed in the first samples (30 to 60 seconds) obtained, increased progressively until cessation of bleeding, and was markedly diminished after heparin administration, thus indicating that thrombin formation occurs early in incisional blood. PF4 increased monotonically throughout blood sampling, whereas the major increase in TxB2 appeared near the cessation of bleeding. The initial increase in FPA content occurred normally in patients with deficiencies of either factor IX or VIII, was markedly diminished in patients with factor X or V deficiency, and was delayed in patients with factor VII deficiency. These studies suggest that tissue factor activation of the classic (activation of factor X) extrinsic coagulation mechanism occurs as an early event during the arrest of bleeding from bleeding time incisions. The relation of the aforementioned to platelet activation is less clear because there was no consistent correlation between decreased FPA formation and impaired PF4 secretion or TxB2 production. In fact, the latter were normal in some subjects with the most impaired FPA formation, which suggests that both collagen and thrombin, perhaps synergistically, may contribute to platelet activation during the primary arrest of bleeding. PMID- 3345343 TI - Increased release of plasminogen activator inhibitor type 2 accompanies the human mononuclear cell tissue factor response to lipopolysaccharide. AB - Human peripheral blood mononuclear cells (PBM) respond to lipopolysaccharide (LPS) with increased release of a plasminogen activator (PA) inhibitor. This response is dose dependent and parallels the LPS-induced expression of PBM tissue factor activity. The PA inhibitors of control and LPS-stimulated PBMs appear identical as both are identified by antibodies to PA inhibitor type 2 of human placenta, but not by antibodies to type 1 inhibitor of bovine aortic endothelial cells. The PA inhibitor is specific for urokinase type PA as determined by the 125I-fibrin plate assay, and direct cleavage of 125I-plasminogen; it does not effectively inhibit tissue-type PA. The inhibitor forms an active site-dependent complex with 125I-urokinase, which then demonstrates an increase in mol wt from 33 kd to 68 kd on reduced sodium dodecyl sulfate (SDS) polyacrylamide gels. PBMs neither secrete nor express active PA. Hence, the exposure of PBMs to LPS results in conditions highly favorable to fibrin deposition and persistence: increased procoagulant and antifibrinolytic activities, accompanied by no measurable PA. Such modulation of these effectors may be important in the pathogenesis of fibrin characteristically found in tissue lesions of endotoxin-initiated processes. PMID- 3345344 TI - Effects of glucose-6-phosphate dehydrogenase deficiency upon sickle cell anemia. AB - We studied the interactions of the A- variety of glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell anemia (HbSS) to see if G6PD deficiency influenced laboratory and clinical features of HbSS. A total of 801 male patients over age 2 had G6PD electrophoresis on cellulose acetate membranes. Assays of both G6PD activity and hexokinase activity were then done on all samples that had an electrophoretic pattern other than the normal wild type (GdB). The collection of clinical data used a standardized protocol. Using cluster analyses we classified 10.4% males to be G6PD deficient, while 18.4% had the functionally normal GdA+ enzyme. The prevalence of G6PD deficiency did not change significantly when age was stratified by decade, suggesting little survival advantage or disadvantage of the combination of G6PD deficiency and HbSS. Compared to patients who were not G6PD deficient, there were no significant differences in the hemoglobin concentration, mean corpuscular volume, reticulocyte count, bilirubin, or SGOT level in patients with HbSS who had G6PD deficiency. The incidence of painful episodes, sepsis, or acute anemic episodes was similar in both groups. Our results are consistent with recent studies of smaller numbers of patients that have found little influence of G6PD deficiency upon HbSS. Specifically, we found no evidence that G6PD enhanced the severity of hemolysis or increased the incidence of acute anemic episodes or sepsis in HbSS. PMID- 3345345 TI - The inactive beta globin gene on a gamma delta beta thalassemia chromosome has a normal structure and functions normally in vitro. AB - We have previously described an English family with gamma delta beta-thalassemia in which a large deletion stops 25 kilobases (kb) upstream from the beta-globin gene locus, and yet the beta-globin gene is inactive in vivo. Affected family members had a beta-thalassemia minor phenotype with a normal hemoglobin A2 level. Gene mapping showed that these subjects were heterozygous for a chromosome bearing a large deletion that began in the G gamma-globin gene, extended through the epsilon-globin gene, and continued upstream for at least 75 kb. The A gamma-, delta-, and beta-globin gene loci on this chromosome were intact. To examine the possibility that an additional defect was present in the beta-globin gene, we cloned, sequenced, and examined the expression of the beta-globin gene from the affected chromosome. No mutation was found in the beta-globin gene sequence from 990 base-pairs 5' to the cap site to 350 basepairs 3' to the polyadenylation signal. The gene was subcloned into an expression vector and introduced into HeLa cells. Analysis of RNA derived from these cells, using a ribonuclease protection assay, revealed qualitatively and quantitatively normal transcription. Thus a structurally and functionally normal beta-globin gene is inactive in the presence of a large deletion more than 25 kb upstream. The loss of beta-globin gene function may be due to disturbance of chromatin conformation caused by the deletion or may be the result of loss of upstream sequences that are necessary for beta-globin gene expression in vivo. PMID- 3345346 TI - Effect of antigen site and complement receptor status on the rate of cleavage of C3c antigen from red cell bound C3b. AB - C3b was bound to human red cells when serum complement was activated by addition of antibodies directed against different red cell antigens, and the rate of cleavage to C3dg was determined by assay for loss of bound C3c antigens using radiolabeled monoclonal anti-C3c. When C3b was bound by antibodies to antigens on branched-chain glycoproteins, cleavage to C3dg occurred more rapidly than when C3b was bound by antibodies to antigens closer to the red cell lipid bilayer. The rate of cleavage to C3dg also correlated directly with the number of complement receptors (CR1) per red cell, reflecting their role as cofactors in the cleavage of iC3b by factor I. Thus, the life span of C3b/iC3b on human red cells, which may be important for determining the rate and mechanism of clearance of C3-coated red cells, appears to depend on the CR1 status of the red cells and the characteristics of the antigen sites around which complement is bound. PMID- 3345347 TI - Immunocytochemical demonstration of gamma-melanocyte stimulating hormone-like immunoreactivity in human neutrophilic granulocytes. AB - Using the indirect immunohistochemical approach the occurrence of gamma melanocyte stimulating hormone (MSH)-like immunoreactivity in neutrophilic granulocytes is described. PMID- 3345348 TI - High-efficiency gene transfer and expression in normal human hematopoietic cells with retrovirus vectors. AB - Retroviral vectors containing the selectable bacterial gene for G418 resistance (neo) were used to demonstrate gene transfer into primary human bone-marrow progenitor cells. To obtain populations of cells in which a high proportion of cells were expressing the neo gene, several important modifications were made to earlier procedures. Cells from normal donors were infected in vitro, were exposed to high concentrations of G418 for two days in liquid culture to enrich for cells expressing the neo gene, and were plated in semisolid medium. Gene transfer and expression were detected in colonies arising from progenitors of granulocyte macrophage and erythroid lineages. Survival curves indicated that a high proportion of progenitor cells, approaching 100%, were G418 resistant. Furthermore, addition of growth factors contained in 5637-conditioned medium to the bone marrow improved the recovery of G418-resistant progenitors twofold to threefold. In addition to these biological measurements of gene expression in progenitor cells, significant levels of neo-specific RNA, similar to the levels of RNA expression in the virus-producing fibroblast cell line, were detected in the bone marrow cells after preselection. These results demonstrate that retrovirus vectors can be used successfully to transfer genes at high efficiency into progenitor cells in the human blood-forming system. PMID- 3345349 TI - Rearrangement and expression of T-cell receptor genes in large granular lymphocyte leukemia. AB - Ten patients with large granular lymphocyte (LGL) leukemia were studied for rearrangement and expression of T cell receptor (TCR) genes. Eight patients with CD3+ LGL proliferation had unique TCR beta-gene rearrangements, supporting a clonal process. Each of five patients studied with CD3+ disease had evidence for expression of full-length TCR alpha-, beta-, and gamma-gene transcripts. In contrast, patients with CD3- LGL proliferation had no evidence for rearrangement or expression of TCR genes. These studies suggest that leukemic LGL arise from two different cell origins. Leukemic LGL may be a useful model for studying natural killer (NK) cell (CD3- LGL) and non-MHC-restricted cytotoxic T lymphocyte (CD3+ LGL) activation and differentiation. PMID- 3345350 TI - Effects of chronic beta-aminoproprionitrile treatment on rat carotid artery. AB - The effects of chronic treatment of young rats (initially 8 weeks old) with the collagen cross-linking inhibitor, beta-aminoproprionitrile (BAPN), on arterial wall properties were studied. BAPN was added to the drinking water for 8 weeks to produce intakes of 0, 100, 200 and 400 mg/kg/day. Systolic pressure of treated animals did not increase with age as rapidly as that of untreated controls. Weight gain of treated animals was inhibited at the highest (BAPN) treatment level. Passive stiffness of isolated, cylindrical segments of carotid arteries was decreased in BAPN-treated animals in a dose-dependent manner. BAPN treatment had no significant effect on the total collagen or elastin content (hydroxyproline) of carotid arteries. Values of maximum active force development to 10 microM norepinephrine plus 75 mM K+ were decreased by BAPN treatment in a dose-dependent manner. There was no significant effect of BAPN treatment on total water content or its cellular and extracellular components in the carotid artery. The relative cell volume of carotid arteries was not altered by BAPN treatment, suggesting that the decreased force development was a characteristic of individual cells. These results suggest that BAPN treatment may decrease stiffness by altering secondary characteristics of the connective tissue matrix without affecting connective tissue content. The decreased maximum smooth muscle force development may be responsible for the blood pressure-lowering effects of BAPN. PMID- 3345351 TI - Scanning electron microscopy of elastic networks from the bifurcation region of guinea pig carotid arteries. AB - We isolated the elastic network from the bifurcation region of guinea pig carotid arteries by treatment with hot alkali and examined its adventitial and adluminal components by SEM. The thickness of networks from common and external carotid arteries averaged 87.5 microns (+/- 6.9 SD) and from the carotid sinus averaged 46.8 microns (+/- 2.4 SD). The networks consisted of a mesh of elastic tissue that became a continuous sheet, 2 microns thick, which formed the internal elastic lamina (IEL). The IEL was fenestrated; the perforations varied in number among the vessels (occipital greater than carotid sinus greater than common = external carotid), and some were spanned by delicate elastic fibers. The IEL's adluminal surface was a smooth membranous sheet, which in some specimens bore unidirectional loose fibers, or was composed of tightly fused bundles of uni- or multidirectional fibers. The interior region of the cranial carotid sinus contained unique blister-like structures and dense clusters of fenestrations, together with a honeycomb-like mesh near the ascending pharyngeal artery. The outer, adventitial elastic layer consisted of a network of loose elastic fibers that were fused with the inner layers. We conclude that the structural differences noted among the common and external carotid arteries and carotid sinus are related to the sinus's unique pressure-sensing functions. PMID- 3345352 TI - Influence of cold-induced increases in sympathetic nerve activity on norepinephrine content in the vasculature of the spontaneously hypertensive rat. AB - In spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), we have examined both the endogenous norepinephrine (NE) contents of caudal arteries, mesenteric arteries and cardiac tissue as well as the rates of decline of NE in these tissues after inhibition of NE synthesis. The endogenous NE contents of caudal and mesenteric arteries from SHR rats were greater than those from WKY rats. In contrast, the NE contents of hearts from SHR and WKY rats were similar. After synthesis inhibition with alpha-methyl-p-tyrosine (300 mg/kg i.p.), the NE contents of hearts and mesenteric arteries decreased in a monoexponential fashion. The rates of decline of NE were similar for corresponding tissues from SHR and WKY rats. Cold stress, reported to selectively activate sympathetic discharge, did not influence the rates of decline of NE in mesenteric arteries of either SHR or WKY animals. In contrast, cold exposure dramatically accelerated the rate of decline of NE in cardiac tissue from both SHR and WKY rats. It is concluded that in mesenteric arteries from SHR rats there is a larger pool of NE with turnover characteristics not dissimilar from that prevailing in vessels from normotensive animals. The failure of cold stress to modify the rates of decline of NE in mesenteric and caudal arteries of SHR and WKY rats suggests that these arteries are under considerable sympathetic influence at ambient temperature. The results support the view that the hypernoradrenergic innervation found in SHR blood vessels, together with normal functioning of the sympathetic nervous system, may have the potential for producing a heightened peripheral vascular resistance in this model. PMID- 3345354 TI - Chronic toxicity of aniline and 2,4-dichlorophenol to Daphnia magna Straus. PMID- 3345353 TI - Does smooth muscle cell polyploidy occur in resistance vessels of spontaneously hypertensive rats? AB - The ploidy of smooth muscle cells (SMCs) enzymatically isolated from the aorta and superior mesenteric artery (elastic arteries), caudal artery (small muscular artery) and the small mesenteric arteries and arterioles (mesenteric resistance vessels) of the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at ages 12, 26, 32 and 40 weeks was determined by flow cytometric DNA analysis and Feulgen-DNA photometric measurements. Frequency of polyploid cells in the aorta and superior mesenteric artery of the SHR increased from 4.43 +/- 1.35 and 7.58 +/- 1.69%, respectively, at 12 weeks to 31.26 +/- 3.00 and 14.13 +/- 1.30% at 40 weeks. There was a smaller increase in the percentage of polyploid cells in these two vessels of the WKY from 4.73 +/- 0.74 and 5.82 +/- 0.33%, respectively, at 12 weeks to 10.64 +/- 0.17 and 7.68 +/- 0.64% at 40 weeks. The caudal artery and mesenteric resistance vessels showed no significant increase in the percentage of 4N (tetraploid) cells in the SHR from 12 weeks (6.80 +/- 0.92 and 6.10 +/- 0.75%) to 40 weeks (7.83 +/- 0.67 and 7.57 +/- 0.07%). Similarly, there was no significant change in ploidy in these arteries of the WKY. Hence, while polyploidy of SMCs increases in the aorta and superior mesenteric artery of the rat with increasing age and with duration of hypertension, there is no significant change in the number of polyploid cells in smaller vessels such as the caudal artery or mesenteric resistance vessels. Since it is the resistance vessels that are involved in the development and maintenance of hypertension, polyploidy of SMCs in the blood vessel wall appears to hold little relevance to the etiology of this disease. As well, increased incidence of polyploidy is not directly attributable to increases in blood pressure as the caudal artery has a high systolic pressure in the SHR yet the incidence of polyploid cells in this artery does not differ from that of the WKY. PMID- 3345355 TI - Effect of environmental pollutants on human semen. PMID- 3345356 TI - Oral and dermal toxicity of MSMA to New Zealand white rabbits, Oryctalagus cuniculus. PMID- 3345357 TI - Chronic dietary toxicity of methylmercury in the zebra finch, Poephila guttata. PMID- 3345358 TI - Temperature-toxicity relationships of fluvalinate (synthetic pyrethroid) on Procambarus clarkii (Girard) under laboratory conditions. PMID- 3345359 TI - Effects of cadmium on some clinical and biochemical measurements in heifers. PMID- 3345360 TI - Increased urinary excretion of tryptophan metabolites in rats exposed to nitrogen dioxide. PMID- 3345362 TI - Toxic effects of phenol on grey mullet, Mugil auratus Risso. PMID- 3345361 TI - Laboratory evaluation of the hazard to wood mice, Apodemus sylvaticus, from the agricultural use of methiocarb molluscicide pellets. PMID- 3345363 TI - Studies of cadmium tolerance in two populations of grass shrimp, Palaemonetes pugio. PMID- 3345364 TI - Volatile nitrosamines in foods and beverages: preliminary survey of the Italian market. PMID- 3345366 TI - Elimination of volatile pollutants from water. PMID- 3345365 TI - Fate of the insecticide chlorfenvinphos in the soil of cauliflower field crops. PMID- 3345367 TI - Enhanced degradation of halogenated hydrocarbons in a water-photolysis system. PMID- 3345368 TI - Survey of diphenyl ether herbicides in dietary foods by the total diet study in Osaka, Japan. PMID- 3345369 TI - Residues of captan and folpet on greenhouse tomatoes with emphasis on the effect of storing, washing, and cooking on their removal. PMID- 3345370 TI - Degradation behavior of captan and folpet on greenhouse tomatoes. PMID- 3345371 TI - Organochlorine and heavy metal residues in falconiforme and ciconiforme eggs (Spain). PMID- 3345373 TI - Abnormal pattern of cerebral blood flow distribution in young alcohol addicts. PMID- 3345372 TI - Changing patterns of cow's milk contamination with organochlorine compounds in Israel (1976-1986). PMID- 3345374 TI - Training alcohol educators: a response to the review by Dianne Hayter. PMID- 3345375 TI - Bolivia and cocaine: a developing country's dilemmas. PMID- 3345376 TI - Alcohol demand and supply management in developing countries. PMID- 3345377 TI - Defining rational prescribing of psychoactive drugs. PMID- 3345378 TI - Drinking sensibly. The search for a 'limit'. PMID- 3345379 TI - Drinking sensibly. The resistance also comes from within. PMID- 3345380 TI - Drinking sensibly. Some relevant research evidence from France. PMID- 3345381 TI - The drug dependence syndrome and related disabilities. PMID- 3345382 TI - Substance misuse and the march of clinical specialism. PMID- 3345383 TI - A follow-up study of Alcoholism Treatment Units: exploring consolidation and change. PMID- 3345384 TI - An evaluation of three treatment programmes for alcoholism: an experimental study with 6- and 8-month follow-ups. PMID- 3345385 TI - Conversation with Dr Pierre Fouquet. PMID- 3345386 TI - Attempted referral as intervention for problem drinking in the general hospital. PMID- 3345387 TI - Drug consumption among university students in Spain. PMID- 3345388 TI - State-dependent retrieval effects with social drugs. PMID- 3345389 TI - The Licensing (Scotland) Act 1976. PMID- 3345390 TI - The Finnish Foundation for Alcohol Studies and the Social Research Institute of Alcohol Studies. PMID- 3345391 TI - Can severely dependent drinkers learn controlled drinking? Summing up the debate. PMID- 3345392 TI - Peer influence and adolescent substance abuse: promising side? PMID- 3345394 TI - An investigation of the ability of young male and female social drinkers to discriminate between regular, calorie reduced and low alcohol beer. PMID- 3345393 TI - Advice versus extended treatment for alcoholism: a controlled study. PMID- 3345395 TI - Changes in methadone withdrawal doses over a five year period: (1982 to 1986). PMID- 3345396 TI - Assessment of opioid dependence with naloxone. PMID- 3345397 TI - Long-term evaluation of controlled smoking as a treatment outcome. PMID- 3345398 TI - Long-term changes in reported alcohol purchasing and consumption following an increase in New York State's purchase age to 19. PMID- 3345399 TI - Effect on traffic accidents of introducing flexible hotel trading hours in Tasmania, Australia. PMID- 3345400 TI - What children know about alcohol and how they know it. PMID- 3345401 TI - Experience with the "floating forehead". AB - The effectiveness of the "floating forehead" operation for treating brachycephaly in infants has been assessed. All children who had undergone this procedure at the Hopital des Enfants Malades between 1977 and 1984 were reviewed retrospectively by an independent observer. Particular attention was paid to the effects on cranial growth, facial growth and morphology. PMID- 3345402 TI - To put the record straight. Use of an abdominal rotation flap for inguinal lymph node dissection. PMID- 3345403 TI - Orbital expansion in plagiocephaly. AB - In moderate to severe plagiocephaly, the transverse diameter of the orbit on the affected side is consistently decreased. In these cases, the supraorbital rim has been expanded by the required amount and bone grafted. This makes for greater orbital symmetry and ease in obtaining the correct supraorbital convexity. Ten patients have been handled in this way with satisfactory postoperative results. PMID- 3345404 TI - Analysis of 200 free flaps. AB - Two hundred microvascular free flaps which were carried out over a period of 13 years 3 months have been analysed from various points of view. Overall survival rate was 94.8% and incidence of re-exploration was 6%. The conclusion obtained from this survey is very simple, namely, the most important factors for successful free flap transfer are a good anastomosis and a reliable flap monitoring system. PMID- 3345405 TI - Is additional epidural sympathetic block in microvascular surgery contraindicated? A preliminary report. AB - The use of additional epidural sympathetic block during and after microvascular surgery in the lower extremities to prevent vasospasm is generally agreed on. However, a significant fall in the perfusion rate of the transplants was seen after application of bupivacaine (Marcain) via the epidural catheter. This effect has, to our knowledge, not been described before and is probably caused by the sympathectomy effect of this type of analgesia. PMID- 3345406 TI - The use of the latissimus dorsi musculocutaneous flap following recurrence of cancer in irradiated breasts. AB - The latissimus dorsi musculocutaneous flap was used to provide chest wall coverage in 40 patients following mastectomy to treat recurrent cancer in irradiated breasts. Although the axillary region had received 50 to 55 grays, the neurovascular pedicle was never jeopardized, thus assuring vascularisation of the flap. In two cases, a small area of skin necrosis in the upper inner border of the flap was observed. Complete healing occurred within weeks. The authors advocate this fast and simple surgical procedure when the quality of the skin and/or the extent of resection prevents primary closure. PMID- 3345407 TI - The amniotic band disruption complex. The pathogenesis of congenital limb ring constrictions; an experimental study in the foetal rat. AB - This paper reports the findings of an experimental foetal rat study which has shown that it is possible to produce mild, moderate and severe limb ring constrictions by simulating the ligature effect of amniotic bands. Of the 40 experimental foetuses, 36 (90%) survived the in utero surgery and are included in the present study. Of these 36 foetuses, limb constriction rings were produced in 35 (97%), and an in utero limb amputation in one (3%). PMID- 3345408 TI - Long microvenous allografts in rabbit femoral arteries and veins. AB - In this study the patency of long microvenous allografts in rabbits with and without immunosuppressive drug therapy was investigated. Eighty-two microvenous autografts (controls) and allografts were transplanted into rabbit femoral vessels. Veno-venous autograft controls were 100% patent at 3 weeks. Rejection of non-immunosuppressed veno-venous allografts consistently produced occlusion between 15-20 days. Thrombus filled the lumen, and a leucocyte invasion destroyed the graft wall. In contrast vein allografts into arteries were 100% patent at 3 weeks; this was reduced to 50% at 4 weeks. Low (5 mg/kg/day) and high (20 mg/kg/day) doses of hydrocortisone over 21 days improved the 3 week patency in veno-venous allografts to 28.5% and 57.0% respectively. Cyclosporin A (15 mg/kg/day) over 8 or 22 days significantly increased the patency rate of veno venous allografts to 100%. Only cyclosporin A treated rabbits maintained allografts of normal vein morphology to 3 weeks. PMID- 3345409 TI - A technique of undermining a V-Y subcutaneous island flap to maximise advancement. AB - A method is described where the planned directional undermining of a subcutaneous triangular flap creates a long pedicle and in the process the flap is "unfolded" to increase its advancement. The flap can be undermined and advanced without any tension. This method is recommended where more conservative undermining is inadequate for mobilisation, particularly in larger defects and in the replacement of skin defects on the lower eyelid which needs to support the eyelid. This technique depends on the richness of the random blood supply in the head and neck regions and the availability of adequate depth of subcutaneous tissue for the development of a long pedicle. Using this method in 53 cases, it has been found possible to advance the flap way past the defect if so desired. Some minor disadvantages of this flap are also described. PMID- 3345410 TI - Reconstruction of the vermilion after "lip-shave". AB - During the year 1986, 12 "lip-shave" defects were reconstructed using orbicularis oris myomucosal flaps, in the Northern Ireland Plastic and Maxillo-Facial Service. Three of these were extended lip-shaves. The planning of a V-Y plasty for myomucusal advancement is described and some representative results are shown. We feel that the myomucosal advancement flap is a valuable technique to overcome some of the problems in reconstruction of the vermilion after lip-shave. PMID- 3345411 TI - A case of Hodgkin's disease arising from an intraglandular lymph node in the parotid gland. AB - Malignant lymphoma of the parotid gland region, especially Hodgkin's disease of the gland, is an extremely rare disorder. We have recently experienced a case initially suspected of being pleomorphic adenoma and later, on postoperative histopathological examination, diagnosed as Hodgkin's disease. The present report describes this case of Hodgkin's disease arising from an intraglandular lymph node in the parotid gland. PMID- 3345412 TI - Bone quality in horses. PMID- 3345413 TI - Infertility in cattle in south-west Scotland caused by an 'intermediate' strain of Campylobacter fetus subspecies fetus (formerly Campylobacter fetus intestinalis). PMID- 3345414 TI - A fresh look at hypomagnesaemia. PMID- 3345415 TI - Poultry--the neglected subject. PMID- 3345416 TI - Ram fertility in south-west Scotland. PMID- 3345417 TI - The clinical pharmacology of agents used to manage cardiovascular instability during general anaesthesia in small animals. PMID- 3345418 TI - Early pregnancy diagnosis in sows by progesterone assay with blood paper method. PMID- 3345419 TI - The influence of a growth promoter (zeranol) on the growth rate, haemogram, myelogram and selected blood biochemical value of calves. PMID- 3345420 TI - The effects of hypocalcaemia on blood gas and acid-base parameters in ruminants. PMID- 3345421 TI - First report of ovine scrapie in Cyprus. PMID- 3345422 TI - Medial hypothalamic stimulation suppresses nociceptive spinal dorsal horn neurons but not the tail-flick reflex in the rat. AB - This study investigated the potential analgesic effects of medial hypothalamic stimulation (HS) on a measure of nocifensive behavior (tail-flick test (TF] in awake rats, and potential inhibitory effects of identical HS on spinal dorsal horn neuronal responses to noxious skin heating in the same animals anesthetized with sodium pentobarbital. Sixty-five male Sprague-Dawley rats implanted with a bipolar stimulation electrode in histologically verified medial hypothalamic sites were tested behaviorally for TF suppression during HS (100 ms trains at 100 Hz, 3/s, 100-1100 microA) in 2-4 consecutive weekly test sessions. Thirty-three of these rats were then used in electrophysiological experiments to record responses of 36 dorsal horn units to noxious skin heating (48-54 degrees C, 10 s/2 min) of the hindfoot pad in the absence of and during HS. Behaviorally, 31/65 rats had no TF suppression at the highest HS intensity tested (1100 microA), 24/65 rats exhibited aversive behavior or motor activity which disallowed reliable TF testing, and only 10/65 rats showed TF suppression in at least one test session. In electrophysiological experiments, the heat-evoked responses of 25/36 dorsal horn units were inhibited to at least 50% of control during HS. The responses of 11 units remained at 65-100% of the control responses during HS of up to 1100 microA. In rats demonstrating TF suppression, 4/7 units were inhibited. In rats with no TF suppression, 10/15 units were inhibited, and in rats showing aversive behavior, 11/14 units were inhibited by HS. These data indicate that although HS suppresses spinal nociceptive neurons, it does not cause reliable TF suppression in unanesthetized rats and bring into question the often-held assumption that stimulation-evoked descending inhibition of spinal nociceptive neurons implies behavioral analgesia. PMID- 3345424 TI - Grafts of pacinian corpuscles reinnervated by dorsal root axons. AB - In adult rats, a piece of the crural interosseous nerve with several Pacinian corpuscles attached was removed from the crural region, autotransplanted onto the surface of the lumbar spinal cord and connected with the peripheral stump of a transected dorsal root. From 10 days up to 6 months after the operation, the grafts were investigated by light and electron microscopy. The regenerating dorsal root axons grew along the grafted nerves into the attached Pacinian corpuscles. By 1-2 months after the operation, the nerves and their branches became almost completely reinnervated by myelinated and unmyelinated dorsal root axons. In a sample of corpuscles examined 2-6 months after grafting, 75% of corpuscles were found reinnervated; each of them was supplied by 1-5 large myelinated axons that formed multiple axon terminals in the inner core. The maximal number of axonal profiles found in a transverse section through different levels of the inner core varied, in individual corpuscles, from 3 to 17 axons and terminals. The dorsal root terminals formed in the grafted corpuscles were mainly filled with mitochondria and resembled peripheral sensory endings. In some instances, the newly formed endings developed lateral processes and membrane specializations characteristic for peripheral Pacinian terminals. Thus regenerating dorsal root axons recognize a grafted peripheral mechanoreceptor as their target and reinnervate it with axon terminals, most of them structurally transformed into peripheral sensory endings. PMID- 3345423 TI - Effects of nocturnal intraperitoneal administration of cholecystokinin in rats: simultaneous increase in sleep, increase in EEG slow-wave activity, reduction of motor activity, suppression of eating, and decrease in brain temperature. AB - Rats received an i.p. injection of cholecystokinin-octapeptide sulfate ester (CCK; 4, 10 or 50 micrograms/kg) or physiological saline at dark onset, and the 24-h sleep-wake cycle (12-h-dark and 12-h-light phases), spontaneous motor activity and brain temperature (Tbr) were recorded. EEG activity was studied through spectral analysis for 2.5 h, and food intake was measured at the end of postinjection hour 1. In response to CCK, non-REM sleep increased at the expense of wakefulness, and the sleep-promoting effect was substantiated by an increase in EEG slow-wave activity. Motor activity, Tbr and food intake decreased. The effects vanished in postinjection hour 2; the diurnal rhythms were not modified. The changes varied as a function of the dose: the effects were significant following 10 micrograms/kg, and even higher in response to 50 micrograms/kg CCK. The results indicate that i.p. CCK definitely promotes non-REM sleep. This effect may belong to the behavioral sequence elicited by the peptide, which is often attributed to satiety. As evidenced by the reduction of Tbr, CCK also exerts strong autonomic actions, which might interfere with the behavioral responses. PMID- 3345425 TI - Septohippocampal disinhibition. AB - Intracellular recordings from CA1 and CA2/3 neurons in rats under urethane anesthesia revealed the following effects of medial septal stimulation (10 pulse trains at approximately 100 Hz): (1) in most cases only minimal signs of any synaptic potential; (2) a marked and prolonged (200-500 ms) depression of on going inhibitory postsynaptic potentials (IPSPs), particularly evident when IPSPs were reversed by Cl- injection; (3) a corresponding increase in input resistance: (4) depolarization when recording with non-Cl(-)-containing electrodes; (5) a predominant hyperpolarization when recording with Cl(-)-containing electrodes; and (6) a marked reduction of the variability of resistance and voltage data. These observations indicate that septal stimulation can strongly depress tonic inhibition in the hippocampus. Septal trains also tended to weaken IPSPs evoked in pyramidal cells by fimbrial stimulation, reducing conductance increase during IPSPs by an average of 42% (S.D. +/- 24.3). Septal inputs to the hippocampal CA1 and CA2/3 regions appear to have a major disinhibitory function. PMID- 3345426 TI - Differential release of vasopressin and oxytocin in response to abdominal vagal afferent stimulation or apomorphine in the ferret. AB - The aim of this study was to investigate whether direct afferent stimulation of the abdominal vagus could promote release of the neurohypophyseal hormones. The nucleus of the solitary tract is the major recipient of vagal afferent information, and this region of the brainstem may also be activated by stimulation of the area postrema. For this reason apomorphine, a D2 dopaminergic agonist which acts on the area postrema, and can evoke vasopressin secretion in man, was also investigated for its effect on vasopressin and oxytocin release. Our results show that vasopressin, but not oxytocin is released in vast amounts in response to electrical afferent stimulation of the abdominal vagus. Administration of apomorphine also evoked a massive vasopressin release with less marked effects on oxytocin. The possible functional implications of these results are discussed especially in the context of nausea and vomiting. PMID- 3345427 TI - Photoendocrine transduction in cultured chick pineal cells: effects of light, dark, and potassium on the melatonin rhythm. AB - Several laboratories have demonstrated the persistence of photosensitive rhythms related to melatonin secretion in cultured chick pineals. We describe here a system using dispersed chick pineal cells in static culture, which displays a rhythm of melatonin release for at least two weeks under cyclic lighting conditions, and for at least 4 cycles under constant red light. Using a rapid and specific extraction assay for the [14C]melatonin formed (from [14C]tryptophan) and secreted by these cells, we have examined the effects of perturbations (light, dark, and potassium) on the amplitude, period, and phase of the melatonin rhythm. The period in constant red light was close to 20 h, but in constant white light (or 12:12 cycles) it was closer to 24 h. Four-hour pulses of white light (in otherwise constant red light) caused an acute fall in melatonin output, and phase-dependent phase shifts of the rhythm relative to controls. Pulses of darkness (in otherwise constant red light) tended to increase melatonin output, and caused phase-dependent phase shifts. Elevated potassium concentrations increased melatonin output and the amplitude of the rhythm, but did not change the period. Four-hour pulses of low (5.4 mM) potassium (in otherwise constant high potassium) mimicked the acute effect of light, reducing melatonin output, but did not induce appreciable phase shifts. Changes in membrane potential appear more likely to be involved in the regulation of melatonin output (and thus be regulated by the pacemaker) than to be involved in regulation of the pacemaker which generates the melatonin rhythm. PMID- 3345428 TI - Corpus callosum: region-specific effects of sex, early experience and age. AB - In infancy, rats were provided handling stimulation and compared at 110 and 215 days of age with non-handled controls. Measurements were made of corpus callosum area, perimeter and length; and width measures were taken at 7 points along the longitudinal axis of the callosum. Callosal size was larger in males than in females, even when adjusted for the larger brain weight of the male. At 110 days handling stimulation increased callosal parameters and resulted in a more regular callosum in males, but this effect was no longer apparent by 215 days. Within the callosum, region-specific effects were found, suggesting that certain callosal fiber populations were involved. Handled males have previously been shown to be more lateralized than non-handled males; thus at least in this experimental system, increased callosal size and regularity is associated with greater hemispheric specialization. PMID- 3345430 TI - Evidence for coexistence of serotonin and noradrenaline in sympathetic nerves supplying brain vessels of guinea pig. AB - Nerve fibers containing 5-hydroxytryptamine (5-HT) were demonstrated immunohistochemically in the wall of pial vessels associated with the circle of Willis in the guinea pig. The fibers formed a network structure which was more dense in the rostral part of the arterial circle and its branches than in the caudal part. The 5-HT immunoreactive fibers disappeared in all arteries studied after bilateral superior cervical ganglionectomy, and unilateral ganglionectomy eliminated the 5-HT immunoreactivity in the ipsilateral part of the middle cerebral, posterior cerebral and superior cerebellar arteries. Decentralization of the superior cervical ganglion had no effect on the perivascular nerve plexus. Subsequent staining with dopamine-beta-hydroxylase (DBH) antiserum following elution of the first antibody revealed that 5-HT was present in the noradrenergic nerve fibers. Small intensive fluorescent cells with positive immunoreaction for 5-HT and DBH, respectively, were located in clusters within the ganglion, which showed no immunohistochemical evidence for the presence of serotonergic neurons. It is concluded that 5-HT is probably not synthesized in truly serotonergic fibers but rather taken up and stored together with noradrenaline in cerebrovascular sympathetic nerves originating in the superior cervical ganglia. PMID- 3345431 TI - Saccadic disorders caused by cooling the superior colliculus or the frontal eye field, or from combined lesions of both structures. AB - We used reversible cold lesions to explore the oculomotor consequences of separate and combined dysfunction of the superior colliculus (SC) and the frontal eye field (FEF). Two monkeys were trained to fixate visual targets. In one we measured visually driven saccades while cooling the right SC, first alone, then in combination with bilateral FEF ablation. Two cryodes in the other subject permitted measurement of eye movements during cooling of either the right FEF or the right SC, or both structures together. Cooling FEF mainly caused a neglect. Raising the cryode temperature slightly alleviated the neglect and uncovered a subtle saccadic deficit. It consisted of a slight reduction in saccadic amplitude and increase in saccadic reaction time. Cooling the SC alone lengthened saccadic reaction time and reduced saccadic amplitude more dramatically, causing the monkeys' initial saccade to miss the target. Some correction occurred but a targeting error persisted to the end of the trial. Combined lesions of FEF and SC greatly increased reaction times, reduced saccadic amplitude, and caused large and persistent targeting errors. The changes in saccadic amplitude and the targeting errors were a function of the monkey's eye position. Combined lesions also truncated the ocular range of the monkeys. PMID- 3345429 TI - Activity of medullary respiratory neurons regenerating axons into peripheral nerve grafts in the adult rat. AB - Autologous segments of peroneal nerve were implanted into the medulla oblongata of young adult rats. To investigate activity of medullary respiratory neurons regenerating axons into these grafts, unitary recording from single fibers was performed on small strands teased from the grafts. Spontaneous activity was observed in teased fibers in 7 of 9 grafts recorded 2-5 months after graft implantation. Respiratory-related activity was found in 5 of these grafts and could in most cases be characterized as emanating from medullary respiratory neurons other than cranial motoneurons. The integrity of the input connections to the neurons that had regenerated axons was manifested by normal patterns of unitary respiratory-related activity and by the responsiveness of firing patterns of these neurons to lung hyperinflation and to the inspiratory off-switch effect induced by vagal stimulation. No spontaneous respiratory activity was found in fibers teased from any of the 10 grafts studied 9-11 months after implantation. Five of these grafts were blind-ended as were the 2-5-month grafts; the other 5 grafts formed bridges between the medulla and C4 ventral horn. No physiologic evidence of functional connections with phrenic motoneurons was found in these bridge grafts. These experiments indicate that physiologic function is maintained or regained in some respiratory neurons regenerating axons into peripheral nerve grafts but that this function is not indefinitely preserved in the absence of functional reconnection with an appropriate target. PMID- 3345432 TI - Motor planning is impaired in Parkinson's disease. AB - Reaction times (RTs) were assessed in parkinsonian and normal subjects under simple ballistic (bRT), simple tracking (tRT), and choice tracking (CRT) ankle plantarflexion RT paradigms. While RTs were prolonged in both groups for tracking versus bRT movements, between-group differences were not detectable for the simple RT (either ballistic or tracking) tasks. In contrast, parkinsonians demonstrated significantly greater CRT and CRT-bRT delays than normals, suggesting that parkinsonian akinesia may involve a disturbance in central processing related to motor planning. PMID- 3345433 TI - The effect of systemic cocaine on spinal nociceptive reflex activity in the rat. AB - In the anesthetized rat, cocaine (25 mg/kg i.p.), enhanced the frequency potentiation of nociceptively evoked polysynaptic discharges but did not affect the polysynaptic reflex discharge to single nociceptive stimuli or the habituation of this reflex to repetitive pinch stimuli. The non-nociceptive, short-latency reflex discharge was suppressed for 10-15 min after cocaine administration. The neurogenic extravasation response to antidromic cutaneous C fiber stimulation was unaffected by cocaine. These findings suggest that systemic cocaine, in doses analgesic for the rat, does not suppress spinal nociceptive reflexes. PMID- 3345434 TI - Priming stimulation of locus coeruleus facilitates memory retrieval in the rat. AB - Rats were trained to run a linear maze for food reinforcement. During the 5-week retention interval, they were implanted under electrophysiological control with fine stimulating electrodes aimed at the nucleus locus coeruleus (LC). When tested 5 weeks after training, control rats showed forgetting in that they made significantly more errors at the test trial than at the last training trial. Low level stimulation of LC immediately before the test alleviated the forgetting in that this group made significantly fewer errors than the non-stimulated group on two successive days. The results are taken as behavioral evidence of a role for noradrenergic projections from LC in memory and attention. PMID- 3345435 TI - Neuronal responsiveness in area 21a of the cat. AB - Photic responsiveness was studied in cells of area 21a which was identified as a region containing few cells projecting to area 17, and was bounded to two other visual areas (posteromedial lateral suprasylvian area and area 19) providing abundant efferent projection to area 17. Area 21a cells were characterized by strong orientation, but demonstrated poor direction and end-stop selectivity, in contrast to strong direction or end-stop selectivity of cells in another two visual areas. PMID- 3345436 TI - Lactic acidosis and recovery of neuronal function following cerebral hypoxia in vitro. AB - The rat hippocampal slice preparation was used to study the combined effects of hypoxia and lactic acidosis on neuronal function. Control slices were exposed to a standard hypoxic insult while being perfused with normal artificial cerebrospinal fluid (ACSF). Experimental slices were perfused with ACSF containing 1.0, 2.0, 10.0 or 20.0 mM lactic acid, 30 min before and during the same standard hypoxic insult. Following at 30-min recovery period the ability of these slices to respond to orthodromic stimulation by displaying a population spike (synaptic function) was tested. No significant decreases in the recovery rate of synaptic function were found between control and experimental groups, excluding the combination of 20 mM lactic acid and 10 min hypoxia, where such a decrease was found. The combination of 10 mM lactic acid and 12 min hypoxia brought about an increase in the recovery rate of synaptic function. Thus, the adverse effects attributed to lactic acid in vivo were not seen in the present in vitro study. Neuronal tissue appears to be able to handle excess lactic acid by yet, unknown mechanism (high intracellular buffer capacity?). The suggested in vivo damage due to lactic acidosis could originate in the cerebrovascular system. On the other hand, the possibility that lactic acidosis is harmless under hypoxic conditions should also be considered. PMID- 3345437 TI - Definition of an extracellular matrix protein in rostral portions of the human central nervous system. AB - We have identified and characterized an extracellular matrix (ECM) glycoprotein of cultured astrocytomas, NEC1, that is expressed in normal human brain parenchyma. Detailed immunohistochemical analysis reveals a region-specific NEC1 pattern along the rostrocaudal axis of the central nervous system (CNS), with strong expression throughout the white matter of telencephalon and diencephalon, scant expression in some areas of mesencephalon, and no expression in pons, cerebellum, medulla, spinal cord, and peripheral nervous system. NEC1 is not co distributed with any known neural cell type, suggesting that expression of specific ECM proteins in the CNS is segmentally controlled. PMID- 3345439 TI - Modification of primary afferent depolarization in cat group Ia afferents following high frequency intra-axonal tetanization of individual afferents. AB - Intra-axonal tetanization of a single, functionally-identified group Ia afferent from the triceps surae muscle in the anesthetized cat produces marked enhancement and slowing of the primary afferent depolarization (PAD) generated in the Ia afferent by volleys in flexor muscle group Ia afferents, plus a pronounced transmembrane hyperpolarizing undershoot (HPU) which disappears more rapidly than the enhanced PAD. These alterations are qualitatively and quantitatively similar to those found after conditioning tetani are applied to the whole muscle nerve. The occurrence of these PAD changes after intra-axonal tetanization of a single group Ia afferent appears to rule out the participation of non-specific alterations in extracellular ionic concentrations or activation of polysynaptic pathways in their genesis. PMID- 3345438 TI - Disinhibition in the rat septum mediated by M1 muscarinic receptors. AB - Acetylcholine (ACh) has been documented as an important central neurotransmitter. We have investigated the actions of ACh within the dorsolateral septal nucleus of the rat to examine its actions within this nucleus, specifically how it may interact to modulate the inhibitory action of gamma-aminobutyric acid (GABA), the known inhibitory transmitter in this area. Our results demonstrate that ACh, acting on M1 muscarinic receptors leads to disinhibition by decreasing GABA release. PMID- 3345440 TI - Long-term potentiation in the dentate gyrus is preferentially induced at theta rhythm periodicity. AB - In urethane-anesthetized rats, high frequency stimulation was applied to the medial perforant pathway at various time intervals (50, 100, 200, 350 and 500 ms) following stimulation of the same pathway by a single pulse of equal intensity. Recordings of dentate gyrus granule cell evoked responses were made to investigate the range of stimuli that are effective in inducing long-term potentiation (LTP). LTP was induced almost exclusively at the 200 ms interval, corresponding to the periodicity of the theta rhythm. Taken in conjunction with similar findings reported in the CA1 field of the hippocampal slice, these results suggest that the correlation between theta rhythm periodicity and LTP is a general phenomenon within the hippocampal formation and lends further support to the hypothesis that the naturally occurring theta rhythm may play a modulatory role in the induction of LTP. PMID- 3345441 TI - Carnosine-like immunoreactivity in the olfactory bulb of the rat: an electron microscopic study. AB - Carnosine-immunoreactive primary olfactory nerve terminals are demonstrated in the glomerular layer of the rat olfactory bulb by immunoelectron microscopy. Asymmetrical synapses between dendrites of mitral/tufted cells and that of periglomerular cells could be observed. In the accessory olfactory system, carnosine-like immunoreactivity is also detected in the vomeronasal neurons. PMID- 3345442 TI - The organization of the cortico-cortical connections between the walls of the lower part of the superior temporal sulcus and the inferior parietal lobule in the monkey. AB - After injections of HRP into area 7a,PG, in the monkey labelled cells have been found in the walls and floor of the lower part of the superior temporal sulcus; the part of area 7a,PG, in the posterior wall of the intraparietal sulcus is connected with the floor and posterior wall of the superior temporal sulcus, and the part of 7a,PG on the surface of the inferior parietal lobule with the floor and anterior wall. Area 7b,PF is related to a restricted part of the floor of the superior temporal sulcus. PMID- 3345443 TI - Decreases of cortical and thalamic glucose metabolism produced by parietal cortex stimulation in the rat. AB - Parietal cortex stimulation elicited focal decreases as well as increases of brain glucose metabolism in ipsilateral cortex, ipsilateral thalamus, and contralateral cortex of rats in a pattern resembling 'surround inhibition'. It is proposed that parietal stimulation activated inhibitory circuits which decreased cortical and thalamic glucose metabolism. This decrease of cerebral glucose metabolism is important for interpreting brain glucose metabolic studies particularly when metabolic changes do not correlate with changes of neuronal activity. PMID- 3345444 TI - The transducer characteristic of hair cells in the human ear: a possible objective measure. AB - We describe here a new kind of non-linear interaction between the responses to two simultaneously presented AM tones. The interaction occurs before the level of binaural convergence, and can be explained in terms of the shape of the inner ear hair cell transducer function. PMID- 3345445 TI - The role of the superior cervical ganglia in the nocturnal rise of pineal type-II thyroxine 5'-deiodinase activity. AB - Superior cervical ganglionectomy (SCGx) abolished the nocturnal rise in pineal type-II thyroxine 5'-deiodinase (5'-D) activity in both euthyroid and hypothyroid rats. Isoproterenol induced at least as great a rise in diurnal pineal 5'-D in SCGx as in intact rats. These data suggest that beta-adrenergic stimulation through the superior cervical ganglia is essential for the nocturnal rise in pineal 5'-D activity. PMID- 3345447 TI - Epidermal growth factor receptor immunoreactivity in rat brain. Development and cellular localization. AB - In rat brain, distinct epidermal growth factor-receptor immunoreactivity (EGFR IR) first appeared in astroglia at about day 16 postnatal, reached maximum intensity at 19 days and then became much weaker as the animals reached adulthood. EGFR-IR was also observed in cerebellar Purkinje cells as early as 11 days postnatal and was maintained into adulthood. In adult and aged animals the most prominent EGF receptor immunostaining occurred in cerebral cortex neurons (layers IV and V) that had the morphology of basket cells. Immunoreactive neurons were abundant in the cingulate, frontal, frontoparietal and striate cortices. In the frontoparietal cortex, EGFR positive neurons were most numerous in the motor area, diminishing laterally towards the somatosensory area. The localization and time of appearance of EGFR-IR did not appear consistent with a direct mitogenic role of the EGF domain in astroglia proliferation during development. However, the EGFR may be involved in neuronal survival and/or neuron-glia signalling. PMID- 3345446 TI - GABA-like immunoreactivity in cholinergic amacrine cells of the rabbit retina. AB - In the ganglion cell layer of the rabbit retina, the inhibitory transmitter gamma aminobutyric acid (GABA) and its analogues are accumulated by neurons that appear to match in size and number the population of displaced amacrine cells that synthesize the excitatory transmitter acetylcholine. In this double-label study, we have established directly that the cholinergic amacrine cells, selectively stained with diamidino-phenylindole, are strongly immunoreactive with GABA antisera. The coexistence of two classical transmitters, one excitatory and the other inhibitory, in this defined neuronal population, suggests that stimulation of the cholinergic amacrines may give rise to complex responses in their target neurons. PMID- 3345448 TI - In vivo studies on the dopamine re-uptake mechanism in the striatum of the rat: effects of benztropine, sodium and ouabain. AB - We used the push-pull perfusion technique to study the in vivo changes in dopamine (DA) levels in the rat striatum in response to treatments which could affect DA re-uptake into the nigrostriatal DA terminals. Benztropine (10(-6) M), a potent DA uptake inhibitor induced a 1.7-fold increase in DA levels in the perfusates compared to basal levels. Perfusion with a Na+-free medium in which Na+ was replaced with either Tris-Cl or choline-Cl in equimolar proportions induced respectively 6.5- and 8.5-fold increases in DA levels in the perfusates. Perfusion of media containing NaCl:Tris-Cl (50:50) or NaCl:choline-Cl (50:50) did not significantly alter the levels of DA in the perfusates. Ouabain (10(-6) M) did not significantly alter DA levels but at a concentration of 10(-4) M, there was a 5.3-fold increase in DA levels in the perfusates compared to basal levels. These results thus demonstrate that the raised DA levels in the extracellular space in response to benztropine is due to the action of the drug in blocking the uptake of DA. The dependence of the uptake mechanism on the presence of Na+ in the external medium and hence on metabolic energy (Na pump) is clearly demonstrated. However, the massive elevation of DA levels under these conditions cannot be due solely to an inhibition of DA uptake but to the carrier-mediated DA exit from cytoplasmic stores resulting from a running down of the ionic gradient. PMID- 3345449 TI - A new class of small inhibitory interneurones in the lamprey spinal cord. AB - Paired intracellular recordings of interneurones and motoneurones have been performed in the lamprey spinal cord in vitro. One new type of small interneurone (10-15 microns in diameter) which produces monosynaptic inhibitory postsynaptic potentials (IPSPs) in motoneurones is described. The IPSP is strychnine-sensitive and thus presumably glycinergic. This type of interneurone undergoes rhythmical membrane potential oscillations during fictive locomotion and intracellular stimulation can have a profound effect on the burst generation occurring during fictive locomotion. PMID- 3345450 TI - Effects of heroin and cocaine on brain activity in rats using [1-14C]octanoate as a fast functional tracer. AB - Brain activity was measured autoradiographically using [1-14C]octanoate (OCTO) as a fast functional tracer in rats receiving either saline, heroin or cocaine. Regional optical densities were normalized to a relative optical density index for comparisons of OCTO labeling between treatment groups. Heroin significantly increased labeling in the dentate gyrus and cocaine increased density in the anterior cingulate cortex, globus pallidus, hippocampus CA3-4, lateral septum, hypothalamus and ventral tegmentum. Heroin and cocaine induced significant, but opposing effects in medial cortex and bed nucleus of the stria terminalis. Both drugs decreased labeling density in the nucleus accumbens and piriform cortex, and increased density in the substantia nigra, subthalamus, medial septum, claustrum, lateral hypothalamus and hippocampus CA2. These results demonstrate the ability of the OCTO method to discriminate the brief metabolic effects of different drug classes, and suggest that heroin and cocaine may activate a common functional system in the brain. PMID- 3345451 TI - Chemically mediated positive feedback generates long-lasting afterdischarge in a molluscan neuroendocrine system. AB - The peptidergic neuroendocrine caudodorsal cells (CDCs) of Lymnaea stagnalis control egg laying. The CDC network consists of 100 electrotonically coupled neurons that form two clusters in the cerebral ganglia. Upon prolonged, repeated, intracellular stimulation of one CDC, excitation spreads over the network and leads to a 30-min period of spiking activity: the afterdischarge. During the afterdischarge a number of peptides, including the ovulation hormone, are released. When two ganglia rings from different animals were pinned down next to each other, an afterdischarge initiated in the CDCs of one CNS activated the CDCs of the other CNS, indicating that excitation spreads in the absence of physical contact between the CDCs. A single isolated intercerebral commissure (COM), the neurohaemal area of the CDCs, displayed the same discharge-inducing capability when brought in the vicinity of a second, intact, CNS. Other parts of the CNS did not possess this property. CDC afterdischarges could also induce repetitive spiking in adjacent isolated CDC somata showing that the effect can be directly on the CDCs themselves. The discharge-inducing factor was well separated from the ovulation hormone on a Bio-Gel P-6 column. The factor was pronase-degradable and inhibitors of proteolytic enzymes increased the factor's longevity. It is concluded that, contingent upon the CDC-discharge, a small (less than or equal to 1500 Da) excitatory peptide is released that acts directly on the CDCs. Its function is argued to be: (1) the spread of excitation from a subset of CDCs, receiving external input, over the entire CDC network; and (2) to provide a positive feedback to generate a maximum (all-or-none) response. PMID- 3345452 TI - Radial-arm maze deficits produced by colchicine administered into the area of the nucleus basalis are ameliorated by cholinergic agents. AB - Rats were given bilateral injections of colchicine into the area of the nucleus basalis. Colchicine produced dose-dependent alterations in the acquisition of a food-reinforced working-memory task. Colchicine-induced deficits in maze performance were attenuated by cholinergic agents, including physostigmine, RS-86 (2-ethyl-8-methyl-2,8-diazospiro-(4,5)-decan-1,3-dione-hydro bromide) and nicotine. Naloxone and vasopressin did not affect radial-arm maze performance of colchicine-treated rats. Subsequent neurochemical analysis showed that colchicine decreased choline acetyltransferase (ChAT) activity and levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the neocortex. However, ChAT activity and other neurochemical measures were not altered in the hippocampus or corpus striatum. Histological assessment indicated damage limited to the injection in the area of the nucleus basalis and enlarged cerebrolateral ventricles. These data suggest the possible utility of the colchicine model in the study of cognitive deficits associated with neurodegenerative diseases. PMID- 3345454 TI - Clutter or contribution to medical literature? PMID- 3345453 TI - Edrophonium-induced inward membrane current in single neurons physically isolated from Aplysia californica. AB - The action of edrophonium on Aplysia neurons was studied using a concentration clamp technique which combines internal perfusion and a rapid drug application. Edrophonium elicited a dose-dependent inward current in the concentration range 10(-6) to 10(-4) M. At higher concentrations (10(-3) and 10(-2) M), the amplitude of the current often decreased and there was a rapid decay of the current. At these high concentrations, the current increased immediately after washing the neuron with normal solution. These results suggest that edrophonium blocks the ion channel which it opens. Removal of Na+ from the external solution greatly reduced the current amplitude by more than 90%. Removal of Ca2+ also reduced the amplitude of the response; however an increase of Ca2+ did not augment the response. These results suggest that Ca2+ does not carry the current, but is necessary for generation of an Na+-dependent inward current. Edrophonium, 10(-2) M, which completely blocked the current it induced within 20 s, did not significantly affect the voltage-dependent Na+ current. Tetrodotoxin, 1 x 10(-6) M, did not affect the edrophonium response. Hexamethonium, 1 x 10(-4) M, did not change the response elicited by edrophonium, while it significantly reduced the ACh response mediated by Na+. In some neurons edrophonium elicited an inward current, but ACh induced an outward current. Therefore the Na+ channels opened by edrophonium appear to be distinct from both the voltage-gated and ACh receptor operated Na+ channels. PMID- 3345455 TI - Multicore myopathy: not always a benign entity. AB - Four patients with Multicore Myopathy, a rare morphologically distinct myopathy, are described. Although previously considered to be a non-progressive or only slowly progressive myopathy, progression to significant disability was seen in three of our cases. The association of cardiac disease with Multicore Myopathy has not been previously emphasised. All four patients in this study had a cardiomyopathy, and heart disease was the cause of death in two of the patients. Multicore Myopathy is not always a benign entity. Cardiac involvement, when present, adversely affects prognosis. PMID- 3345456 TI - Tizanidine versus baclofen in the treatment of spasticity in patients with multiple sclerosis. AB - Tizanidine (Sirdalud) was compared to baclofen (Lioresal) in a randomized, double blind, cross-over trial. Each medication was introduced over a three week titration period and then maintained at the highest tolerated dose for five weeks. The two treatment phases were separated by a one week drug withdrawal and a two week washout period. Sixty-six patients entered the trial and forty-eight completed both treatment phases. At the end of the trial, neurologists and physiotherapists thought that baclofen was superior on the basis of perceived efficacy and tolerance (p less than or equal to 0.05). Although the efficacy of tizanidine or baclofen was judged as good to excellent by 24 and 39% of patients respectively, this difference was not statistically significant. Muscle weakness was the most common adverse effect. This was significantly more troublesome in patients treated with baclofen. Somnolence and xerostomia were more common in patients treated with tizanidine. Both baclofen and tizanidine appear to be useful adjuncts in the treatment of spasticity in patients with multiple sclerosis. Preference of either drug is tempered principally by side-effects. PMID- 3345457 TI - gamma-Aminobutyric acid (GABA) and sepsis-related encephalopathy. AB - In order to determine whether disturbances in GABA homeostasis might play a role in the pathogenesis of sepsis-related encephalopathy, serum and brain tissue GABA concentrations from six areas of the brain (cortex, diencephalon, striatum, hippocampus, midbrain, and pons-medulla) were determined in a rat model of bacterial sepsis (cecal ligation and perforation). The results were compared to those obtained from sham operated control animals. All septic animals demonstrated clinical signs of encephalopathy and had elevated serum GABA levels (0.92 +/- 0.3 uM versus 0.48 +/- 0.15 in controls, p less than 0.01). GABA content in the specific subcompartments of the brain, however, were similar in the two groups. These results indicate that although serum GABA levels are elevated during sepsis, GABA is unlikely to play an important role in the pathogenesis of sepsis-related encephalopathy. PMID- 3345459 TI - Normality and disease. AB - There have been trends to equate normal with an ideal state of health, and disease with disturbances that are determined solely by subclinical abnormalities. While in any living language there is a conflict between established definition and the need for change, modification in the use of words that are of such central importance to medical writing requires cogent justification that has not been forthcoming in these instances. To avoid further obscuration of the literature, the term normal should be limited to its traditional connotation of average, and the term disease should be reserved for disturbances of health that are clinically manifest. PMID- 3345458 TI - Multimodal evoked potential studies in leukodystrophies of children. AB - Evoked potentials were studied in 22 children with leukodystrophy [10 metachromatic leukodystrophy (MLD), 4 Pelizaeus-Merzbacher (PM), 3 Krabbes, 2 adrenoleukodystrophy (ALD), and one each of Alexander's, Canavan's and multiple sulphatase deficiency (MSD) diseases]. The ABRs were abnormal in all patients (except for the younger ALD), but varied with the type of leukodystrophy. The PM and Krabbes patients had abnormal ABRs with a loss of the rostral waves, accompanied in Krabbes with delayed I-III interpeak latencies; in MLD, ALD and MSD prolonged interpeak latencies were found. Three patients who had no clinical signs, but were positively diagnosed as MLD on the basis of absent arylsulphatase A, also had abnormal ABRs. The SEPs were abnormal in all patients. Cortical SEPs were absent in 16 and abnormal in 5 who were in the earlier stages of their disease. Cervical SEPs were within normal limits except for the Krabbes and MLD patients studied, who showed peripheral slowing. The VEPs were normal in only 6 and, unlike the ARBs and SEPs, did not seem to covary with clinical severity across the various leukodystrophies but did correlate with disease progression. Thus, multimodal EPs are useful in the diagnostic differentiation of the leukodystrophies. PMID- 3345460 TI - Treatment of dopaminomimetic psychosis in Parkinson's disease with electroconvulsive therapy. AB - Two Parkinsonian patients with chronic nonconfusional dopaminomimetic psychosis were treated with a course of electroconvulsive therapy. In both cases sustained remission of psychosis was obtained in the face of ongoing administration of dopaminomimetics. PMID- 3345461 TI - Primary hypothyroidism presenting as growth delay and pituitary enlargement. AB - We report the case of a young boy being considered for pituitary surgery because of pituitary enlargement found during assessment of growth delay. There was no goitre but he was hypothyroid clinically and biochemically. The finding of an elevated TSH suggested primary thyroid disease with thyrotroph hyperplasia. Treatment with L-thyroxine resulted in prompt resolution of his pituitary enlargement and improvement in his visual fields. PMID- 3345462 TI - Treatment of syringomyelia with a syringosubarachnoid shunt. AB - The surgical results in 40 patients with syringomyelia, treated with a syringosubarachnoid shunt or other procedures are reviewed. The principal indication for surgery was that of significant neurological deterioration. There were 12 patients with idiopathic syringomyelia without tonsillar ectopia, 12 with an associated Chiari malformation, 11 with post-traumatic syringomyelia and five patients with spinal arachnoiditis. There were 38 syringosubarachnoid shunts performed in 35 patients, and an excellent or good result was achieved in 26 patients (74.3%). In terms of the type of syringomyelia, the best results were obtained in the idiopathic group without tonsillar ectopia and in the post traumatic group. A short duration of pre-operative symptoms favoured a better outcome, and in our opinion, early surgical treatment is indicated for all patients with neurological deterioration. All eight patients in whom a posterior fossa decompression was performed as the initial surgical procedure required a second operation, either a syringosubarachnoid or syringoperitoneal shunt to achieve neurological improvement or stabilization. Thus, the syringosubarachnoid shunt is an effective therapeutic modality for patients with syringomyelia, particularly for the idiopathic and post-traumatic groups. More than one surgical procedure may be required to achieve cessation of deterioration. Overall, excellent or good results were achieved in 29 (72.5%) of the 40 patients. PMID- 3345463 TI - Electrophysiological monitoring during acoustic neuroma and other posterior fossa surgery. AB - Techniques used to monitor the function of the seventh and eighth cranial nerves during acoustic neuroma and other posterior fossa surgery are reviewed. The auditory brainstem response (ABR), electrocochleogram (ECochG) and direct recording from the auditory nerve (CNAP) were compared. The best technique is the ECochG, although in many cases, the CNAP should be used as a back-up technique. The CNAP is especially useful for the identification of the auditory nerve. Both can provide real-time feedback on the physiological integrity of the auditory nerve. The ABR may be helpful in monitoring brainstem function. For some procedures, optimal monitoring requires the combined recording of all three techniques. Monopolar constant-voltage intracranial stimulation of the facial nerve is helpful for the identification and preservation of the facial nerve. Audio monitoring of spontaneous electromyographic activity provides real-time feedback on the effect of surgical manipulation of the nerve. Monitoring of ephaptic transmission in the facial nerve during microvascular decompression for hemifacial spasm aids in the identification of the offending vessel. PMID- 3345464 TI - Spectral analysis of the EEG in craniocerebral trauma. AB - The objectives of the present study were to evaluate the relationship between the fractional amplitudes of the EEG derived from power spectral analysis (PSA) of the electroencephalogram (EEG) and depth of coma measured clinically with the Glasgow Coma Score, and to assess the accuracy of PSA in predicting long-term outcome. Thirty-two patients rendered unconscious by blunt head injury (mean (GCS = 7) had intermittent EEG recordings daily from 1-10 days post injury. There was a significant correlation between fractional amplitude of the EEG and the GCS. The rate and magnitude of change in the EEG and GCS were also correlated. There were significant differences in PSA parameters between improved and deteriorated patient groups at the termination of monitoring (p = .02) and in the change of PSA parameters over time (p = .02). Using linear discriminant analysis of PSA parameters, the accuracy of outcome prognostication based on the six month outcome was approximately 75%. Accurate classification of outcome was possible in a number of patients in whom there was little or no change in the GCS during the period of monitoring. PMID- 3345465 TI - Trichlorethylene poisoning mimicking multiple sclerosis. PMID- 3345467 TI - Transmission of HIV. PMID- 3345466 TI - Spontaneous temporary remission in primary CNS lymphoma. PMID- 3345468 TI - Removal of esophageal foreign bodies with a Foley catheter under fluoroscopic control. PMID- 3345470 TI - Medical apartheid in Canada. PMID- 3345469 TI - The crisis at Baragwanath. PMID- 3345471 TI - Measuring the blood glucose level. PMID- 3345472 TI - Toxic ocular effects of ethambutol. PMID- 3345473 TI - A fish story. PMID- 3345474 TI - Drug treatment of opioid dependence. PMID- 3345475 TI - Production of clinical notes in personal injury litigation in Ontario. PMID- 3345477 TI - Acute intravascular hemolysis after a platelet transfusion. PMID- 3345476 TI - Desktop analysers: quality of results obtained by medical office personnel. AB - We carried out a study to evaluate the quality of results obtained by 14 nontechnical medical office personnel using desktop analysers. The instruments evaluated were the Reflotron analyser, the Seralyzer, the Vision analyser and the DT60 analyser. For precision studies low and high concentrations of control materials were used. For correlation studies the results obtained by the office personnel were compared with those obtained by a trained technologist. The coefficient of variation for the office personnel ranged from 3.0% to 8.1% with the Reflotron analyser, from 6.3% to 26.5% with the Seralyzer, from 1.0% to 4.1% with the Vision analyser and from 1.4% to 16.7% with the DT60 analyser. The correlation coefficient ranged from 0.970 to 0.997 with the Reflotron analyser, from 0.779 to 0.997 with the Seralyzer, from 0.975 to 0.998 with the Vision analyser and from 0.963 to 0.995 with the DT60 analyser. The proportion of results obtained by the office personnel that differed by more than 10% from those obtained by the technologist was 7% with the Reflotron analyser, 42% with the Seralyzer, 2% with the Vision analyser and 21% with the DT60 analyser. The instruments whose operation involves the least number of steps gave the most reliable results in the hands of medical office personnel. PMID- 3345478 TI - Guidelines for measles control in Canada. PMID- 3345479 TI - Not willing to be "figurehead", surgeon general quits armed forces. PMID- 3345480 TI - AIDS in Ireland. PMID- 3345481 TI - Abortion: a debate that cannot be ducked or stalled. PMID- 3345482 TI - AIDS and organized medicine: our profession has failed to lead. PMID- 3345484 TI - Common clinical challenges in geriatrics. PMID- 3345483 TI - Treating hypertension in the elderly. AB - This article discusses various topics related to treating hypertension in the elderly, including pseudohypertension, systolic hypertension, characteristics of young and elderly hypertensive patients, diagnostic considerations in evaluating elderly hypertensive patients, and general therapeutic considerations. PMID- 3345485 TI - Treatment of advanced and recurrent squamous carcinoma of the uterine cervix with constant intraarterial infusion of cisplatin. AB - Twelve patients with primary or locally recurrent squamous carcinoma of the cervix were treated with constant internal iliac artery infusion of cisplatin (CDDP) via a totally implantable chemotherapy pump. Seven previously untreated patients received standard external and interstitial radiotherapy (RT) in conjunction with CDDP infusion. Five patients with isolated pelvic recurrences received CDDP therapy only. The chemotherapy pump was refilled weekly on an outpatient basis. All nine evaluable patients developed unilateral or bilateral lower extremity pain which responded to dosage reduction. No renal or marrow toxicity was seen. Both of the evaluable patients treated for recurrent tumor died 32 and 60 weeks after initiation of treatment. The seven patients treated primarily with RT + CDDP infusion include one who expired with persistent tumor and one with no evidence of disease (NED) after exenteration for a pelvic recurrence at 48 and 85 weeks respectively. The five remaining patients are NED at 12 to 60 weeks. Constant internal iliac artery infusion of CDDP via an implantable chemotherapy pump can be performed with acceptable toxicity. The preliminary results suggest that further study in previously untreated undergoing concurrent radiotherapy is warranted. PMID- 3345486 TI - 4-Hydroxytamoxifen binds to estrogen receptors and inhibits the growth of human endometrial cancer cells in vitro. AB - Effects of 4-hydroxytamoxifen, a major metabolite of tamoxifen, on the proliferation of cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in primary culture. Competitive binding studies showed that 4-hydroxytamoxifen effectively binds to cytoplasmic estrogen receptors (ER) in uterine adenocarcinomas. Of 20 endometrial adenocarcinomas examined, five tumors were successfully grown in primary cell culture. The addition of 4-hydroxytamoxifen (1 nmol/l to 1 mumol/l) in a medium supplemented with estrogen-free serum resulted in a dose-dependent inhibition of the growth of cancer cells in two tumors having ER. However, 4-hydroxytamoxifen did not affect the growth in the culture system of the remaining three tumors, in which ER were absent in two tumors but were present in one. These results strongly suggest that tamoxifen has a direct growth-inhibitory effect on human endometrial adenocarcinoma possibly through ER in the tumor. PMID- 3345487 TI - Effects of tamoxifen on blood coagulation. AB - Sixteen patients with clinically localized breast carcinoma who had been receiving tamoxifen 20 mg twice daily for between 3 and 38 months (median, 14 months) were studied. Several parameters of coagulation (antithrombin III, protein C, fibrinopeptide A and in vitro monocyte procoagulant activity) were investigated in this group and compared to a group of 15 patients with clinically localised breast carcinoma not given tamoxifen. Tamoxifen did not induce significant changes in these parameters to account for the reported thromboembolic events associated with this therapy. The reduced antithrombin III activity previously described in patients receiving tamoxifen for metastatic breast cancer may reflect disease activity rather than a direct effect of tamoxifen on blood coagulation. PMID- 3345488 TI - Evaluation of the role of radiotherapy in the management of carcinoma of the buccal mucosa. AB - Carcinoma of the buccal mucosa is the commonest intraoral malignancy in south India. This article concerns the results of radiotherapy in cancer of the buccal mucosa. Radiotherapy was used as the first line of management in this series and surgery was reserved for failures even though very few patients opted for salvage surgery. Of the 234 evaluable patients, 42% survived disease-free at the end of 3 years with radiotherapy alone. Eighty-five percent of the patients with Stage I, 63% with Stage II, 41% with Stage III, and 15% with Stage IV disease survived disease-free at 3 years. With radium implant and small-volume beam-directed external radiotherapy, the survival rates were similar (62% versus 64%). The results of external radiation in advanced disease were dismal. Persistent disease after radiotherapy was a serious problem in advanced stages, especially in view of nonacceptance of salvage surgery by a significant proportion of patients. The most effective way of improving cure rates in cancer of the buccal mucosa seems to be early detection. PMID- 3345489 TI - Whole abdominal irradiation for tumors of the uterine corpus. AB - Between November 1981 and December 1985, 16 patients with high-risk tumors of the uterine corpus were treated with a postoperative course of whole abdominal-pelvic irradiation. Thirteen patients had carcinomas and three had sarcomas. All patients had complete pelvic surgery including extrafascial (or modified radical) hysterectomy and bilateral salpingo-oophorectomy, pelvic node sampling, evaluation of peritoneal cytology, and resection of extrauterine metastases when indicated. All patients were free of gross visible tumor after surgery. Target doses of radiation were 3000 cGy to the upper abdomen and 4500 cGy to the pelvis. Median follow-up was 24 months for survivors (range, 17 to 63 months). The disease-free survival and overall survival at 17 months was 50%. Six of the 16 (38%) patients suffered intraabdominal relapse. One patient had a significant complication (bowel perforation). The data from this pilot study suggest that whole abdominal-pelvic irradiation may be useful only in the management of some patients with few high risk features of endometrial carcinoma. Patients with extensive extra-uterine involvement and with sarcoma histology do not appear to benefit from this experimental therapy. PMID- 3345490 TI - Effects of hepatic arterial yttrium 90 glass microspheres in dogs. AB - A 22-micron glass microsphere called TheraSphere (Theragenics Corp., Atlanta, GA) has been developed in which yttrium 89 oxide is incorporated into the glass matrix and is activated by neutron bombardment to form the beta-emitting isotope yttrium 90 (Y 90) before using the spheres as radiotherapeutic vehicles. The injection of up to 12 times (on a liver weight basis) the anticipated human dose of nonradioactive TheraSphere into the hepatic arteries of dogs was well tolerated and produced clinically silent alterations within centrolobular areas. The hepatic arterial (HA) injection of radioactive TheraSphere also produced portal changes similar to those observed in humans after external beam therapy. While the extent of damage increased with the delivered dose, radiation exposures in excess of 30,000 cGy did not cause total hepatic necrosis and were compatible with survival. No microspheres distributed to the bone marrow and absolutely no myelosuppression was encountered in any animal. Proposed hepatic exposures to humans of 5000 to 10,000 cGy by means of these microspheres, therefore, would appear to be feasible and tolerable. Radiotherapeutic microsphere administration preceded by regional infusion of a radiosensitizing agent and/or immediately following the redistribution of blood flow toward intrahepatic tumor by vasoactive agents can potentially yield a synergistic, highly selective attack on tumors confined to the liver. PMID- 3345491 TI - Primary malignant melanoma of the rectum. Evidence for origination from rectal mucosal melanocytes. AB - Reports of rectal melanoma often attribute the lesion to tumor extension from anal melanocytes which have undergone malignant transformation while the existence of true primary melanoma of the rectum has been disputed. This dispute primarily relates to past inability to demonstrate normal melanocytes in rectal mucosa. In this case report, two polypoid melanomas clearly located in the rectum were discovered at sigmoidoscopy. Thorough histologic examination failed to demonstrate atypical anal melanocytes, and the presence of normal melanocytes in the rectal mucosa was confirmed by electron microscopy and immunohistochemistry. Although rare, it appears that primary malignant melanoma may arise from melanocytes among columnar rectal epithelium. PMID- 3345492 TI - Prognostic value of histologic factors in adult cerebral astrocytoma. AB - Surgical specimens from 165 adults with cerebral astrocytoma were reviewed to establish the prognostic value of histologic factors when studied both individually and in combination. Glioblastomas were excluded. Nine morphologic parameters and 25 clinicotherapeutic factors were correlated with survival. Cell density, endothelial hyperplasia, number of mitoses X 10 high-power field (HPF), and vessel frequency appeared to be highly significant prognostic factors (P less than 0.001). Nuclear polymorphism, microcysts, and vessel size were significant moderately (P less than 0.01). Microcysts, vessel size, endothelial hyperplasia, and number of mitoses X 10 HPF remained significant statistically after a multivariate analysis that also included clinicotherapeutic factors. Survival was similar for astrocytomas with "extensive malignancy" and astrocytomas with only "slight and localized malignancy." Multivariate analysis showed that the presence or absence of malignancy was more important prognostically than the clinical variables (i.e., postoperative Karnofsky status or extent of surgical removal). PMID- 3345493 TI - Resectable adenocarcinoma of the rectosigmoid and rectum. I. Patterns of failure and survival. AB - In an effort to determine the patterns of failure and survival of rectosigmoid and rectal cancer, a retrospective review of 168 patients who underwent potentially curative surgery at the New England Deaconess Hospital was performed. The 5-year actuarial survival for the entire group was 67%. Survival rates decreased with increasing penetration of the bowel wall by tumor and the presence of lymph node metastasis, but only the latter reached statistical significance. Those patients who underwent an abdominoperineal resection also experienced a significant decrease in survival compared to a low anterior resection. Patterns of failure, expressed as the actuarial incidence of first failure at 5 years, were examined by stage. With the exception of stages B3 and C3, there was a trend towards increased abdominal, distant, and total failure with increasing bowel wall penetration by tumor. A similar trend was seen in local failure in those patients with positive nodes. Knowledge of these data may help identify those patients who may benefit most from adjuvant therapy. PMID- 3345494 TI - Resectable adenocarcinoma of the rectosigmoid and rectum. II. The influence of blood vessel invasion. AB - Several series have examined the influence of blood vessel invasion (BVI) by tumor on survival of patients with colorectal cancer; however, little data are available regarding its influence on patterns of failure. In an effort to determine the influence of BVI on the patterns of failure and survival in rectosigmoid and rectal cancer, a retrospective review of 168 patients who underwent potentially curative surgery at the New England Deaconess Hospital was performed. In patients who had tumors with extramural BVI, there was a significant decrease in five-year actuarial survival compared with patients who had tumors with intramural BVI or were BVI-negative (BVI-). When the intramural and extramural types of BVI were combined, no significant impact was noted on the patterns of failure or survival in patients with BVI+ versus those with BVI- tumors. In contrast, the presence of lymphatic vessel invasion was found to significantly decrease survival. By using a proportional hazards analysis, it was found that BVI was not an independent prognostic variable. Therefore, the use of BVI alone is not recommended for selecting patients with rectosigmoid and rectal cancer who may benefit from adjuvant therapy. PMID- 3345495 TI - Multivariate analysis of prognostic factors in regional cutaneous metastases of extremity melanoma. AB - In 135 patients with regional cutaneous recurrence of extremity melanoma, the prognostic significance of 12 clinical and pathologic variables was analyzed in four alternative Cox stepwise regression models and by single variable analysis. A highly significant fit of the regression (P less than 0.01) identified four factors that particularly influenced survival: the presence of intradermal or mixed (as opposed to purely subcutaneous) metastases (P less than 0.001), sex (P = 0.032), excision of regional cutaneous metastases with or without perfusion (P = 0.033), and the presence of subcutaneous metastases (P = 0.201). Not predictive of survival were age at diagnosis; site of primary; anatomic location, number, size, or distance from the primary of the regional cutaneous metastases; time since primary treatment; number of positive regional lymph nodes; and single- or triple-drug perfusion. PMID- 3345496 TI - Patient compliance with aggressive multimodal therapy in locally advanced breast cancer. AB - This study of compliance was performed to determine whether a medically indigent population with breast carcinoma that has been neglected is an appropriate group for inclusion in an aggressive combined treatment program. After incisional biopsy, 28 locally advanced breast cancer (LABC) patients received two cycles of cytoxan, Adriamycin, 5-Fluorouracil, and tamoxifen (CAFT) followed by a simple mastectomy and level I axillary dissection. After surgery, patients received four additional cycles of CAFT alternating with three cycles of 15 Gy to the chest wall and regional lymphatics. Compliance was defined as overall compliance, the percentage of patients completing the protocol as described; and appointment compliance, the ratio between treatments or appointments attended versus those scheduled. Overall compliance was 75% (21 of 28 patients). The total number of appointments scheduled was 1054 (mean, 37 +/- 2), and the total attended was 965 (mean, 34 +/- 3), giving an appointment compliance rate of 91.7%. Compliance did not vary significantly with age, marital status, nationality, the presence of complications, or delay to diagnosis. Compliance did decrease significantly with time. There was 100% overall compliance at 2 months, 82% at 6 months, and 75% at 1 year. We conclude that although our patients had neglected their disease and were medically indigent, they were highly motivated patients once in therapy. This suggests that complex treatment regimens are feasible as well as effective for the treatment of LABC. PMID- 3345497 TI - Unusual breast masses. The sequential development of mammary tuberculosis and Hodgkin's disease in a young woman. AB - A left breast mass developed in association with pulmonary tuberculosis in a woman 26 years of age. Eight years later, rapidly fatal Hodgkin's Disease with chest wall erosion by involved mediastinal nodes simulating a breast lump developed. Subsequently, a discrete breast mass due to mammary Hodgkin's disease developed. Involvement of the breast by both tuberculosis and Hodgkin's disease, two diseases often associated with immune dysfunction, in a patient with dysmorphic features and a strong family history of tuberculosis, raises the possibility of an underlying genetic defect. This defect probably involves the immune system. PMID- 3345498 TI - Salvage radical prostatectomy for adenocarcinoma of the prostate. AB - Radiotherapy has been a major method of treating localized carcinoma of the prostate. It is becoming increasingly apparent that failures of radiotherapy do occur and can be predicted by postradiation biopsy. Salvage radical prostatectomy can be offered to these patients. The authors report on five patients with residual carcinoma after radiotherapy. Three patients had undergone external-beam radiotherapy and two had undergone interstitial plus external-beam radiotherapy. All salvage radical prostatectomies were uncomplicated technically. One patient had a myocardial infarction believed to be unrelated to the procedure. Two patients, observed for over 1 year, have mild residual stress incontinence but residual adenocarcinoma proved to be localized to the surgical specimen in all but one patient. One patient underwent nerve-sparing radical prostatectomy and has had return of sexual function. Salvage radical prostatectomy is a viable option for patients who have histologically proven residual carcinoma after definitive radiotherapy. PMID- 3345499 TI - Polyps of the colon in Barcelona, Spain. An autopsy study. AB - This study is based on a prospective survey of 212 autopsies that was conducted to determine the prevalence of colon adenomas in Barcelona, Spain. Adenomatous polyps were found in 21.7% of the patients (29.3% of the men and 12.5% of the women); multiple adenomas were found in 40% of the patients. Almost all adenomas were less than 5 mm in diameter, although 6.7% of the ones seen predominantly in the rectosigmoid colon were larger than 1 cm. The prevalence and number of adenomas increases with age. The prevalence of hyperplastic polyps was very low (1.6%). The data shows a relationship between the prevalence of colon adenomas in Spain and the incidence of colon cancer. The prevalence of colon adenomas in Spain is one of the lowest compared with that in other European countries and North America. PMID- 3345500 TI - Familial fragile 8q22 involved as a cancer breakpoint in cells of a large bowel tumor. AB - A familial fragile 8q22 and an interferon-induced fragile 16q22 were found in two sisters. Eight years previously, both sisters developed an endometrial adenocarcinoma and now one of them presented with an adenocarcinoma of the colon. An 8q22 deletion was found in all the cells of the colonic tumor and seemed to be the primary initiating change. Other nonrandom and possibly promoting aberrations were also present, among others, a 16q22 deletion. The possibility exists that a familial fragile 8q22 may predispose to cancer and a fragile 16q22 may have promoting capacities. PMID- 3345501 TI - The fragile site hypothesis of cancer. PMID- 3345502 TI - Oncogene location update. PMID- 3345503 TI - Fragile sites in leukemic bone marrow cells. PMID- 3345504 TI - Nasal tumours in rats after short-term exposure to a cytotoxic concentration of formaldehyde. AB - Male Wistar rats were exposed to 0, 10 or 20 ppm formaldehyde vapour for 4, 8 or 13 weeks (6 h/day; 5 days/week), and were then observed for periods up to 126 weeks. Transient growth retardation occurred in both test groups. Death rate was not noticeably affected by formaldehyde. Despite recovery periods of at most 126 weeks, the nasal respiratory and olfactory epithelium of many rats of the 20 ppm group exhibited non-neoplastic histopathological changes. Similar but much less severe changes of the respiratory epithelium were seen in a small number of rats of the 10 ppm group; the olfactory epithelium was not visibly affected in rats of this group. Nasal tumours considered to be induced by formaldehyde were seen only in the 20 ppm group and mainly in rats that had been exposed for 13 weeks, the incidence being 4.5% (6/132). These tumours comprised 3 squamous cell carcinomas, 1 carcinoma in situ and 2 polypoid adenomas, all originating from respiratory epithelium. It was concluded that rat nasal respiratory epithelium severely damaged by formaldehyde vapour often does not regenerate and in some cases develops tumours. PMID- 3345505 TI - Metabolism of benz[j]aceanthrylene (cholanthrylene) and benz[l]aceanthrylene by induced rat liver S9. AB - The metabolites of benz[j]aceanthrylene (B[j]A) produced by incubation with liver S9 proteins from rats induced with Aroclor-1254 and phenobarbital have been identified as: trans-B[j]A-1,2-dihydrodiol, B[j]A-9,10-dihydrodiol, B[j]A-11,12 dihydrodiol, and 10-hydroxy-B[j]A. The major metabolite formed (58-60%) by both induced S9 preparations was trans-B[j]A-1,2-dihydrodiol, the cyclopenta-ring dihydrodiol while oxidation at the k-region or the proximal-bay region was minor. There were no statistical differences in individual or total B[j]A metabolite rates between the 2 induced S9 preparations. B[l]A was metabolized by Aroclor 1254 and phenobarbital induced rat liver S9 preparations to trans-B[l]A-1,2 dihydrodiol, B[l]A-7,8-dihydrodiol, and B[l]A-4,5-dihydrodiol. The major B[l]A metabolite formed (28-40%) by both induced S9 preparations was B[l]A-7,8 dihydrodiol, the k-region dihydrodiol. Cyclopenta-ring oxidation to trans-B[l]A 1,2-dihydrodiol was approximately 50% of that observed for k-region oxidation. Both induced S9s produced similar rates of B[l]A metabolites except for B[l]A-7,8 dihydrodiol formation which was higher for Aroclor-1254-induced S9. PMID- 3345506 TI - The occurrence of preformed N-nitroso compounds in food samples from a high risk area of esophageal cancer in Kashmir, India. AB - Several commonly used raw foodstuffs from a high risk esophageal cancer region in Kashmir (India) were analysed for the presence of N-nitroso compounds. The food items were selected on the basis of their frequent consumption with particular emphasis on the preserved foods (dried, pickled and smoked) and those which are unique to the region. Nine out of 11 food items were found to contain low concentrations of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N nitrososarcosine (NSAR), N-nitrosoproline (NPRO) and N-nitrosothaizolidine-4 carboxylic acid (NTCA). The preliminary survey shows a widespread contamination of N-nitroso compounds in raw foodstuffs from Kashmir. PMID- 3345507 TI - Induction of beta-glucuronidase activity during dimethylhydrazine carcinogenesis and additive effects of cholic acid and indole. AB - The kinetic change of beta-glucuronidase (beta-G) activity was measured in mouse large intestinal mucosa during dimethylhydrazine (DMH) carcinogenesis with addition of cholic acid and/or indole. The experiment lasted 21 weeks. The enzyme activity began to increase significantly at 5th week after treatment of DMH with cholic acid and/or indole, and at 7th week with DMH alone. Then, increased activity remained the rest of the time. Mouse intestinal cancer induced by DMH injection are also shown to have an increased beta-G activity. The induction of beta-G activity in the early stage of DMH colon carcinogenesis and additive effects of cholic acid and/or indole may imply one mechanism of action of DMH as a carcinogen and cholic acid as a promoter in large intestinal cancer. PMID- 3345508 TI - Induction of ornithine decarboxylase and histidine decarboxylase activities in rat colon mucosa after application of 12-o-tetradecanoylphorbol-13-acetate (TPA), sodium deoxycholate and indole. AB - Ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) activities of rat colon mucosa were induced after intrarectal instillation of 12-o tetradecanoylphorbol-13-acetate (TPA) and sodium deoxycholate. After instillation of sodium deoxycholate, ODC and HDC activities increased rapidly and reached a peak at 4 h, then decreased quickly towards control levels. Both enzymes activities also increased significantly 4 h after instillation in animals treated with TPA and sodium deoxycholate plus indole. However, there were no changes in ODC and HDC activities from 0-8 h after indole administration. These data are the first to show the induction of HDC activity in colon mucosa by TPA and sodium deoxycholate and suggest that the induction of activities in these two enzymes might be one mechanism of their action as cancer promoters. PMID- 3345510 TI - Clastogenic and cytotoxic effects of spermine oxidation products in mouse lymphoma L5178Y cells. AB - Treatment of mouse lymphoma L5178Y cells with spermine in Fischer's medium containing bovine serum lead to formation of chromatid aberrations. The cause of this effect seems to be that bovine serum contains spermine oxidase which catalyzes oxidation of spermine to unstable aldehyde derivatives (oxidized spermine) and hydrogen peroxide. Fraction of chromatid aberrations induced by oxidized spermine was estimated in experiments in which the cells were treated with spermine or a stoichiometric amount of hydrogen peroxide in the presence and in the absence of catalase. Cytotoxicity of oxidized spermine was evaluated by clonogenic assay. PMID- 3345509 TI - Rapid development of hepatocellular neoplasms in aging male C3H/HeNCr mice given phenobarbital. AB - One hundred and nineteen male C3H/HeNCr mice, 12 months of age, with spontaneous preneoplastic and neoplastic hepatocellular lesions were given phenobarbital (PB) at 500 ppm in drinking water. Groups of 9-10 mice were sacrificed after 12, 24 and 36 weeks of PB exposure. Identical numbers of untreated controls were used. A group of 6-week-old C3H/HeNCr mice were also given PB and sacrificed at 12, 24 or 36 weeks. In aging mice, PB exposure significantly increased the number of gross tumors or microscopic foci, adenomas or carcinomas per liver at all time periods, especially unique eosinophilic proliferative lesions, while young mice did not develop any focal proliferative lesions by 36 weeks. These findings suggest that in aging mice a fraction of the hepatocyte population (normal, spontaneously initiated or preneoplastic) is more highly susceptible to phenobarbital 'carcinogenesis' than are hepatocytes of younger mice. PMID- 3345511 TI - Sixth annual ECP (European Organization for Cooperation in Cancer Prevention Studies) symposium. International symposium on gastric carcinogenesis. London, March 7-8, 1988. Abstracts. PMID- 3345512 TI - Epoxide-metabolizing enzymes in mammary gland and liver from BALB/c mice and effects of inducers on enzyme activity. AB - Epoxide hydrolases (EC 3.3.2.3) (EH) are hydrolytic enzymes which may play an important role in the activation and detoxification of mammary carcinogens. In this study, microsomal, cytosolic, and cholesterol epoxide hydrolases along with glutathione S-transferase were characterized in liver and mammary gland from nulliparous and lactating BALB/c mice and from mice transplanted with preneoplastic hyperplastic outgrowths. Clofibrate, butylated hydroxyanisole, and beta-naphthoflavone were used to induce EH. Significant epoxide hydrolysis was observed in microsomal and cytosolic subcellular fractions assayed with cis- and trans-stilbene oxide, benzo(a)pyrene-4,5-oxide, and cholesterol epoxide. The hydrolysis rates were significantly different for nulliparous and lactating animals, in both mammary gland and liver. Clofibrate increased the activity of all forms of EH in liver, but not mammary gland. Butylated hydroxyanisole and beta-naphthoflavone appeared to induce cytosolic glutathione S-transferase as well as some, but not all, forms of EH in liver and mammary gland regardless of hormonal stimuli. The inducers produced different effects in mammary gland as compared with liver. This may be due to either differing amounts of inducer reaching the target site or different regulation of the enzymes in mammary gland and liver. Hyperplastic outgrowths and liver from hyperplastic outgrowth transplanted animals demonstrated significantly different EH and cytosolic glutathione S-transferase activities from those of nulliparous and lactating animals. This observation offers preliminary evidence that levels of epoxide metabolizing enzymes are altered when mammary tissue is transformed. Mammary gland cytosolic EH was purified by affinity chromatography and compared to that from liver by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, enzyme-linked immunosorbent assay, isoelectric focusing, and enzyme inhibition by 4-phenylchalcone oxide. Cytosolic EH from the mammary gland appears to be identical to the liver enzyme by all the above mentioned biochemical and biophysical parameters. PMID- 3345513 TI - Identification of cell surface cathepsin B-like activity on murine melanomas and fibrosarcomas: modulation by butanol extraction. AB - Cathepsin B (CB) is a lysosomal cysteine protease that may play a role in the activation of extracellular degradative enzymes involved in the destruction of the subendothelial matrix and extravasation of metastatic tumor cells. In this study we have investigated the cell surface expression of a CB-like enzyme on the surface of tumor cell variants expressing both high and low metastatic potentials. Cell surface CB-like activity was demonstrated by incubation of intact viable cells and isolated plasma membranes with the selective chromogenic substrate N-carbobenzoxyvalyllysyllysylarginyl-4-methoxy-beta-naphthylamide. Cell surface CB activity required thiol activation and was blocked by the CB-selective protease inhibitors leupeptin, antipain, and L-trans-epoxysuccinylleucylamido(4 guanidino)butane, but not by inhibitors inactive against CB. Enzymatic activity was significantly reduced when assayed at pH 7 and greater. Although all tumor lines had detectable CB-like activity, we observed a correlation between the expression of cell surface CB-like activity and metastatic phenotype only with isolated plasma membranes, and not with whole cell preparations. Noncytolytic 2% butanol extraction, a technique known to increase the experimental metastatic propensity, also significantly increased cell surface CB-like activity. Incubation of extracted tumor cells with crude butanol extracts prepared from those cells restored the cell surface CB-like activity to that of the unextracted controls, suggesting that the increased enzyme activity observed following extraction may be due to the release of an endogenous cysteine protease inhibitor. These results demonstrate that a CB-like protease is expressed on the surface of several murine tumor cells and that an endogenous inhibitor may play a role in determining experimental metastatic phenotype. PMID- 3345514 TI - Nucleoside restoration of heat resistance and suppression of glucose-regulated protein synthesis by glucose-deprived L929 cells. AB - Depriving cultured cells of glucose increases glucose-regulated protein synthesis, suppresses heat shock protein synthesis, and increases sensitivity to killing by hyperthermia. The present study shows that supplementation of glucose free culture medium with uridine or a number of other nucleosides reverses all these effects of glucose deprivation. Uridine is more effective in this regard than equimolar concentrations of glucose, and ribose is relatively ineffective. Uridine does not suppress glucose-regulated protein synthesis that has been induced by glycosylation inhibitors, calcium chelation, or anoxia. We infer from these data that the effects of glucose deprivation may result from inhibition of ribonucleoside synthesis and that ribonucleosides may be directly involved in regulating glucose-regulated protein and heat shock protein synthesis as well as in protecting cells against hyperthermic cytotoxicity. PMID- 3345515 TI - Radiohalogenation of a monoclonal antibody using an N-succinimidyl 3-(tri-n butylstannyl)benzoate intermediate. AB - N-Succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE) was elevated for its utility in the radiohalogenation of monoclonal antibodies. The F(ab')2 fragment of monoclonal antibody OC 125 was labeled with 125I using the ATE reagent and with 131I using a conventional electrophilic iodination method (Iodogen). N Succinimidyl 3-[125I]iodobenzoate was synthesized from ATE in greater than 90% yield and purified using a disposable silica gel cartridge. About 60-65% of the radioiodinated product was coupled to the F(ab')2 fragment after a 30-min reaction. Two procedures were investigated, one involving exposure of antibody to 35 nmol of ATE and the other to 240 nmol of ATE. Using Scatchard analyses, affinity constants for binding to CA 125 antigen for OC 125 F(ab')2 labeled using the low ATE, Iodogen, and high ATE procedures were determined to be (5.2 +/- 1.0) x 10(10), (2.5 +/- 0.9) x 10(10), and (4.2 +/- 2.4) x 10(9) M-1, respectively. Paired-label studies in athymic mice bearing OVCAR-3 tumors treated with injections of antibody labeled via both ATE and Iodogen demonstrated that use of the ATE method (a) reduced thyroid uptake to less than 0.1% of the injected dose, more than 100 times less than that observed with Iodogen; (b) resulted in more rapid clearance of activity from normal tissues; and (c) with the low ATE preparations, increased the uptake of radioactivity in tumor from 27 to 49%. At 96 h, tumor:tissue ratios were generally at least 4-fold higher when antibody was labeled via ATE. These results suggest that the ATE method may be a valuable approach for the radiohalogenation of antibodies. PMID- 3345516 TI - Involvement of soybean agglutinin binding cells in the lymphatic metastasis of the R3230AC rat mammary adenocarcinoma. AB - Many human tumors, such as those of the breast, metastasize initially via the lymphatics. The tumor cell surface is believed to play a critical role in this process. To study the cell surface properties involved in dissemination, the poorly metastasizing R3230AC rat mammary adenocarcinoma was enriched for metastasizing cells by excising rare lymph node metastases arising after the s.c. injection of 10(6) cells and reinjecting these cells into another series of rats. By repeated enrichment cycles, the frequency of lymphatic metastasis was increased from 10 to 60-100% of the animals given injections. Fluorescein conjugated lectins were used to probe the tumor cell surface. It was found that the percentage of cells in the population able to bind high levels of the lectin, soybean agglutinin (SBA), increased from 11 to almost 80% in the highly metastatic, enriched cell populations. A linear correlation (r = 0.92; P less than 0.001) was found between the percentage of cells in the population which bound high levels of SBA and the frequency of lymphatic metastasis in a series of enriched cell lines. Clones which bound high levels of SBA metastasized to lymph nodes at a high frequency, while clones which bound only low amounts of SBA exhibited a low frequency of lymphatic metastasis regardless of the metastatic potential of the cell line from which the clones were isolated. The binding of SBA to the cell was reduced by preincubation of the lectin with galactose, completely blocked by incubation with N-acetylgalactosamine, and unaffected by incubation with glucose or mannose, demonstrating that SBA was recognizing a N acetylgalactosamine-containing component of the cell surface. Cells enriched for lymphatic metastasis were not similarly enriched for hematogenous metastasis. While cell lines enriched for lymphatic metastasis have been previously described, this is the first report of a specific cell surface property, SBA binding, associated with lymphatic metastasis. PMID- 3345517 TI - Enhancement of metastatic capacity of fibroblast-tumor cell interaction in mice. AB - A low metastatic clone, G6, was isolated from the B16 melanoma cell line by cloning procedure. When the cells were cultured in vitro with fibroblasts from newborn mice, the lung-colonizing potential of G6 cells was substantially increased. The effect of coculture depended on the number of the fibroblasts. The elevated colonizing potential of G6 cells was reversed to the original low potential by subculturing them for 20 days without the fibroblasts. The culture medium conditioned by G6-fibroblast coculture demonstrated an activity to enhance the lung-colonizing potential of G6 cells, whereas the medium from the culture of fibroblasts alone showed only a little activity. The growth rate and plating efficiency of G6 cells cultured with the fibroblasts or in the conditioned medium did not differ from those of uncocultured G6 cells. The potentiating activity in the conditioned medium was nondialyzable and stable to heating at 80 degrees C for 10 min, but was lost after heating for 10 min at 120 degrees C, or by the treatment with trypsin. These results indicate that the enhancement of lung colonizing potential of G6 cells could be mediated by a soluble factor(s) released from cocultured fibroblasts. PMID- 3345518 TI - Functional role of platelets in experimental metastasis studied with cloned murine fibrosarcoma cell variants. AB - The involvement of platelets in experimental metastasis was studied with cloned cell lines derived from PAK 17, a recently induced methylcholanthrene-induced C57BL/6 mouse fibrosarcoma. Tumor cell-induced platelet aggregation and lung colonization assays were used to distinguish three major stable phenotypes among the clones: a low metastatic-low platelet aggregating type, e.g., clone PAK 17.12; a low metastatic-high platelet aggregating type, e.g., clone PAK 17.14; and a high metastatic-high platelet aggregating phenotype, e.g., clone PAK 17.15. Clones with high metastatic but low platelet aggregating potential were not observed in the study. Intravenously injected PAK 17.14 and PAK 17.15 cells, but not PAK 17.12 cells, induced greater than 50% reductions in circulating platelet levels in C57BL/6 mice. Since highly metastatic clone PAK 17.15 cells consistently induced high levels of tumor cell-induced platelet aggregation regardless of the platelet donor, it was selected to study the relationship between its tumor cell-induced platelet aggregation and lung colonizing abilities. (a) A 93% decrease in lung colony number resulted in mice injected with 100 micrograms of prostacyclin immediately before injection of clone PAK 17.15 cells. Prostacyclin was also able to inhibit, in a dose dependent fashion (0-5 ng), platelet aggregation induced by clone PAK 17.15 cells in vitro. (b) A 92% reduction in lung colony number occurred in mice showing marked thrombocytopenia following injection of 100 micrograms of rabbit anti-mouse platelet antibody 24 h before tumor cell injection. (c) A greater than 80% reduction in clone PAK 17.15 lung colony number was observed in mice rendered thrombocytopenic by i.v. injection of 0.038 units of neuraminidase 24 h before i.v. injection of 10(5) tumor cells. These results suggest that platelets are required for successful lung colonization by clone PAK 17.15 cells. However, the presence in this fibrosarcoma of high platelet aggregating-poorly metastatic cells, such as clone PAK 17.14, demonstrates that while the ability to aggregate platelets is necessary for successful metastasis by some tumor cells, it is insufficient if tumor cells lack other critical properties required for completion of the metastatic cascade. PMID- 3345519 TI - Influence of retinoids on growth and metastasis of hamster melanoma in athymic mice. AB - The effects of 2-hydroxyethyl retinamide, N-(4-hydroxy-phenyl) all-trans retinamide, and 13-cis-retinoic acid on the growth and metastasis of a malignant hamster melanoma cell line HM1-F5 was determined in a double blind study using 4- to 5-week-old male NIH Swiss and BALB/c derived athymic nu/nu mice. Mice were fed retinoids (0.75 and 1.0 or 1.5 mmol/kg diet) or a placebo diet ad libitum beginning on the day of s.c. inoculation of 5 x 10(5) HM1-5 cells. Tumor incidence, latency, and growth rate were similar in both strains of mice. All placebo-treated mice had lung metastasis on the day of autopsy, although the total number of metastases was lower in NIH Swiss derived athymic mice. While mean tumor incidence and latency were not significantly altered by any retinoid treatment, tumor growth rate (volume) and final tumor weight were inhibited (P less than 0.05) by 0.75 mmol/kg 13-cis retinoic acid and 1.5 mmol/kg N-(4 hydroxyphenyl) all-trans-retinamide. In contrast, at 1.0 or 1.5 mmol/kg diet, 2 hydroxyethyl retinamide had no significant effect on tumor growth rate. 13-cis retinoic acid, 0.75 mmol/kg, 2-hydroxyethyl, 1.0 mmol/kg, and N-(4 hydroxyphenyl), 1.0 mmol/kg significantly reduced the mean number of metastatic lesions in NIH Swiss derived mice, but N-(4-hydroxyphenyl) all-trans-retinamide also reduced metastatic incidence while 2-hydroxyethyl retinamide and 13-cis retinoic acid had no effect. A concentration of 1.5 mmol/kg diet of 2 hydroxyethyl and N-(4-hydroxyphenyl) all-trans-retinamide significantly reduced the overall number of gross lung metastases in BALB/c and Swiss mice, and mean number of metastases in Swiss mice. Analysis of correlation indicated that the inhibitory effect of high-dose N-(4-hydroxyphenyl) and 2-hydroxyethyl retinamide on metastasis was not associated with (independent of) any inhibitory effect on primary tumor invasiveness or growth rate. Our observations suggest that agents such as retinoids have an antimetastatic potential. PMID- 3345520 TI - Specificity, schedule, and proliferation dependence of infused L-histidinol after 5-fluorouracil in mice. AB - L-Histidinol, an analogue of the amino acid L-histidine, has been reported to be able to increase the specificity of 5-fluorouracil (FUra), through both protection of normal tissues at risk and potentiation of leukemic cell killing. It is postulated that this occurs through prevention of the entry of normal cells into the cell cycle through protein deficiency, while allowing malignant cells, permissive for protein starvation, to continue to cycle, thus maintaining sensitivity for cycle specific anticancer agents. Reported in this paper is the confirmation of these L-histidinol-FUra effects. However, a modification was made by which more L-histidinol could be given and more consistent protection of whole animals demonstrated. Further, an optimal schedule of L-histidinol was defined in which FUra preceded L-histidinol infusion. Finally, the specificity and proliferation dependence of this schedule was evaluated on colony forming units spleen in resting and proliferating state, colony forming units-granulocyte macrophage, and L1210 leukemia. This demonstrates that the FUra/L-histidinol combination indeed protects only normal cells but that the postulated proliferation dependence is absent, indicating an alternate biological mechanism. PMID- 3345521 TI - Effect of galactose on systemic hemodynamics and blood flow rate in normal and tumor tissues in rats. AB - The effect of galactose on systemic hemodynamics and blood flow rate of Walker 256 carcinomas and several normal tissues of unanesthetized, unrestrained female Sprague-Dawley rats was measured, using the radioactive microsphere technique, prior to and at 30 and 60 min after galactose administration (6 g/kg body weight, i.v.). Whereas heart rate remained unchanged following injection, cardiac output (CO) and cardiac index decreased by 35% (P less than 0.05). Mean arterial pressure immediately decreased during the injection but then increased reaching a value 10% (P less than 0.05) above the baseline 30 min following injection. Stroke volume (SV) decreased by 30% (P less than 0.05) and total peripheral resistance increased by 65% (P less than 0.05). Redistribution of blood flow, expressed as %CO, among normal tissues was seen to the brain, kidneys, liver, jejunum, and hindlimb muscle and away from the pancreas, stomach, and skin. Changes in %CO to the spleen, colon, forelimb muscle, and peritumor tissue were not significant. Blood flow rate in most normal tissues either decreased or remained constant following injection. An exception was in the liver where blood flow significantly increased. Blood flow significantly decreased in the tumor (approximately 60%) and this reduction in blood flow was larger than the reduction in CO. These results suggest that (a) the effect of galactose on systemic hemodynamics and blood flow rate are similar to those produced by glucose; (b) reduction in blood flow rate in tumors is due to both systemic and local effects; and (c) changes in blood flow to normal tissues should not be disregarded when using galactose in combination with hyperthermia and/or chemotherapy for cancer treatment. PMID- 3345522 TI - Effects of 1-beta-D-arabinofuranosylcytosine incorporation on elongation of specific DNA sequences by DNA polymerase beta. AB - 1-beta-D-Arabinofuranosylcytosine (ara-C) is an effective antileukemic agent which acts as an inhibitor of DNA synthesis. The precise mechanism responsible for this inhibitory effect, however, remains unclear. The present work has examined the effects of the triphosphate derivative, ara-CTP, on purified DNA polymerase beta. These studies were performed on M13 phage DNA templates of defined sequence. The results demonstrate that ara-C is incorporated into DNA by DNA polymerase beta. The results also demonstrate that the incorporated ara-C residue acts as a relative chain terminator. Moreover, the relative chain terminating effects of ara-C are sequence specific. In this regard, DNA strand elongation was progressively slowed at sequences of two, three, and four contiguous sites for cytosine incorporation. We also demonstrate that the inhibitory effects of ara-C are reversed by competition with deoxycytidine triphosphate for incorporation into the DNA strand. Taken together, these findings are consistent with structural differences of the incorporated arabinosyl moiety which alter reactivity of the 3'-terminus and thereby inhibit chain elongation. These findings also provide new insights regarding the inhibitory effects of ara-C on elongation of specific DNA sequences. PMID- 3345523 TI - Metabolism of N-nitrosodialkylamines by human liver microsomes. AB - The metabolism of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine, N nitrosobenzylmethylamine, and N-nitrosobutylmethylamine was investigated in incubations with human liver microsomes. All of the 16 microsomal samples studied were able to oxidize NDMA to both formaldehyde and nitrite at NDMA concentrations as low as 0.2 mM; the rates of product formation of the samples ranged from 0.18 to 2.99 nmol formaldehyde/min/mg microsomal protein (median, 0.53 nmol). At a concentration of 0.2 mM NDMA, the rates of denitrosation (nitrite formation) were 5 to 10% (median, 6.3%) those of demethylation (formaldehyde formation); the ratio of denitrosation to demethylation increased with increases in NDMA concentration, in a similar manner to rat liver microsomes. Immunoblot analysis with antibodies prepared against rat P-450ac (an acetone-inducible form of cytochrome P-450) indicated that the P-450ac [P-450j (isoniazid-inducible form)] orthologue in human liver microsomes had a slightly higher molecular weight than rat P-450ac and the amounts of P-450ac orthologue in human liver microsomes were highly correlated with NDMA demethylase activities (r = 0.971; P less than 0.001). Analysis of four selected microsomal samples showed that human liver microsomes exhibited at least three apparent Km and corresponding Vmax values for NDMA demethylase. This result, suggesting the metabolism of NDMA by different P 450 enzymes, is similar to that obtained with rat liver microsomes, even though most of the human samples had lower activities than did the rat liver microsomes. The high affinity Km values of the four human samples ranged from 27 to 48 microM (median, 35 microM), which were similar to or slightly lower than those observed in rat liver microsomes, indicating that human liver microsomes are as efficient as rat liver microsomes in the metabolism of NDMA. The human liver microsomes also catalyzed the dealkylation and denitrosation of other nitrosamines examined. The rates of product formation and the ratios of denitrosation to dealkylation varied with the structures and concentrations of the substrates as well as with the microsomal samples tested. The results indicate that human liver microsomes are capable of metabolizing N-nitrosodialkylamines via the pathways that have been established with rat liver microsomes. PMID- 3345524 TI - Detection of patients with cancer by monoclonal antibody directed to lactoneotetraosylceramide (paragloboside). AB - A hybridoma producing monoclonal antibody (H11) directed to lactoneotetraosylceramide (paragloboside) has been established from spleen cells of a mouse immunized with paragloboside. The monoclonal antibody H11 (immunoglobulin M type) was selected from five clones showing different reactivities with paragloboside. The monoclonal antibody was highly specific to paragloboside and lacked reactivity with other glycolipids including glucosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, and GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4Glc beta 1-1Cer. However, the monoclonal antibody (H11) was found to bind to lactosamine-containing glycolipids at their terminals, such as i- and I-type glycolipids as well as paragloboside. A two-step sandwich radioimmunoassay method for paragloboside antigen in serum was established by using the monoclonal antibody. The mean paragloboside antigen concentration in the sera from 20 normal individuals was 25.3 ng/ml. If the cutoff value was set at 80.9 ng/ml [25.3 + 2 x 27.8 (SD)], only 1 of 20 healthy controls had an elevated paragloboside value in the serum, whereas sera from 9 of 12 (75.0%) hepatoma, 4 of 10 (40%) pancreatic cancer, 16 of 40 (40.0%) stomach cancer, and 6 of 10 (60%) lung cancer patients had elevated paragloboside values. Sera from 3 of 8 hepatitis patients and 7 of 10 liver cirrhosis patients were estimated to be positive but sera from 16 patients with benign disease had paragloboside levels lower than the cutoff value. A larger amount of the antigen was found in liver metastases from colorectal carcinoma compared to the normal counterpart. The antigen was also detected in the medium of various human cancer cells and meconium. However, the antigen in the sera, medium, meconium, and cancer tissue seemed to be associated with glycoprotein or lipoprotein, because most of the antigen activity was eluted in the void volume fraction on high performance liquid chromatography with a gel filtration column. PMID- 3345526 TI - Carcinogenicity of hydroxyalkylnitrosamines in F344 rats: contrasting behavior of beta- and gamma-hydroxylated nitrosamines. AB - The carcinogenicity of N-nitrosomethyl-(2-hydroxyethyl)amine (NMHEA), N nitrosomethyl-(3-hydroxypropyl)amine (NMHPA), and the p-toluenesulfonate (tosylate) ester of NMHEA (NMHEATs) was tested in male and female F344 rats. The chemicals (25.6 mumol per application) were administered by twice-weekly gavage in corn oil (0.2 ml) for the lifetime of the animals. NMHEA was found to be an effective carcinogen under those conditions. The median survival time for the females was 9 mo after treatment was initiated, while for the males it was 12 mo. The principal cause of death of the females was hepatocellular carcinoma (14 of 20), while only 6 of 20 male rats exhibited that tumor. A few of the male rats had squamous cell carcinomas of the nasal epithelium (4 of 20), tumors which were not observed in the females. NMHPA was a much weaker carcinogen. Many of these rats survived for 2 yr and most had many age-related cancers. Nevertheless, 10 of the NMHPA-treated males and 2 females had adenocarcinoma of the lung, which was absent in the controls and also induced a significant number of neoplastic nodules in the livers of rats of both sexes. NMHEATs was also a weak carcinogen. However, besides many age-related tumors, it induced some hepatocellular carcinomas as well as hemangiosarcomas of the liver. NMHEATs was at least partially hydrolyzed to NMHEA, which was detected in the blood plasma of treated rats. A hypothesis has been advanced that NMHEA is activated to a proximate carcinogen by sulfate conjugation of the hydroxyl group; the present data do not contradict this hypothesis. The relatively lower carcinogenic potency of NMHPA, the different tumor spectrum induced by this chemical, and particularly the differences in chemical behavior suggest that its mode of activation is not the same as that for NMHEA. PMID- 3345525 TI - Sporadic amplification of the HER2/neu protooncogene in adenocarcinomas of various tissues. AB - The HER2/neu protooncogene was found to be amplified in 6 of 109 primary adenocarcinoma tumors. No HER2/neu amplification was found in 29 other primary nonadenocarcinomatous tumors. In two colon tumors, in addition to the amplification, DNA rearrangement of HER2/neu gene was also observed. The rearrangement was explored in detail in one tumor and it was shown to be confined to the 3' region of the gene. Moreover, this tumor expressed an aberrant HER2/neu polypeptide with a molecular weight of 190,000, which is larger by approximately 5,000 than the molecular weight of the normal HER2/neu protein. The aberrant HER2/neu protein was immunoprecipitated with site-specific antibodies against a synthetic peptide from the COOH-terminal end of the normal HER2/neu protein; it also displayed intrinsic protein tyrosine kinase activity leading to self phosphorylation. PMID- 3345527 TI - Alkylation of DNA in rats by N-nitrosomethyl-(2-hydroxyethyl)amine: dose response and persistence of the alkylated lesions in vivo. AB - The in vivo alkylation of DNA by N-nitrosomethyl-(2-hydroxyethyl)amine (NMHEA) was examined in male and female F-344/N rats. NMHEA is a strong hepatocarcinogen in female rats when administered by gavage but a weaker hepatocarcinogen in male rats. Groups of 5 rats of each sex were treated by gavage with various doses of NMHEA dissolved in corn oil. After 4 h the animals were sacrificed and the livers, lungs, and kidneys were removed. The DNA from each liver was isolated and the neutral thermal and mild acid hydrolysates were separated by high-performance liquid chromatography. The alkylated guanines were quantified by fluorescence spectroscopy. NMHEA gives rise to four fluorescent alkylated guanines, 7- and O6 methylguanines, and 7- and O6-hydroxyethylguanines. The dose-response data revealed that all four lesions increased with dose. There was approximately 10x more methylation than hydroxyethylation at the 7 position of guanine. There was less O6 alkylation, but both methylation and hydroxyethylation were observed at all of the doses studied. The overall alkylation was the same in males and females at the 10- and 20-mg/kg doses, but at higher doses the females exhibited significantly higher levels of alkylation than males. The level of alkylation of DNA isolated from non-target tissues, lung, and kidney was low. The persistence of these lesions in vivo was studied at a dose of 25 mg/kg. Groups of five animals each were sacrificed at various times from 0 to 96 h. There was no significant difference between the sexes in persistence of any of the lesions in the liver. The 7-alkylguanines disappeared slowly over the observation period. 7 Methylguanine was present at 30% of the maximum level after 96 h, while 7 hydroxyethylguanine appeared to be more stable. The O6-alkylguanines were removed rapidly from the liver, being at base level by 48 h. The rapid removal of O6 hydroxyethylguanine suggests a repair process independent of O6-alkylguanine-DNA guanine alkyl transferase: an excision repair is postulated. In vitro alkylation of calf thymus DNA by N-nitrosomethyl-(2-tosyloxyethyl)amine, a surrogate for the putative O-sulfate conjugate of NMHEA, resulted in exclusive methylation of DNA guanine at both the 7 and O6 positions; no hydroxyethylation was detected. In vitro alkylation of calf thymus DNA with 2-hydroxyethyl-ethylnitrosourea resulted in exclusive hydroxyethylation of DNA-guanine at the 7 and O6 positions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3345528 TI - Alterations in whole body, muscle, liver, and tumor tissue protein synthesis and degradation in Novikoff hepatoma and Yoshida sarcoma tumor growth studied in vivo. AB - The rate of protein synthesis in vivo was assessed in tumor tissue, skeletal muscle, liver, and the whole body of rats bearing either the Yoshida sarcoma or Novikoff hepatoma after 18 days of tumor growth and compared to tumor-free controls. Changes in size of the whole animal and tumor (i.e., growth) were measured, and fractional rates of growth, synthesis, and degradation were estimated. Muscle protein synthesis and whole-body growth were significantly reduced in both groups of tumor-bearing rats after 18 days of tumor growth. In addition to reductions in muscle protein synthesis, whole-body protein synthesis was significantly reduced in the Yoshida tumor-bearing group (587 +/- 36 versus 401 +/- 40 mg/h; mean +/- SEM; control versus Yoshida group, respectively, P less than 0.01). Tumor protein synthesis was not statistically different between the Yoshida tumor (76 +/- 21 mg/h) and the Novikoff tumor (50 +/- 8) after 18 days of growth despite the fact that the Yoshida tumors were significantly larger (33.9 +/- 4.2 g versus 11.9 +/- 1.2 g; P less than 0.01). The fractional synthesis rate (Ks) was, in fact, significantly slower in the Yoshida versus the Novikoff tumor (36.8 +/- 7.6 versus 55.1 +/- 4.8%/day). Tumor growth (Kg) followed first order growth rates for both tumor types (r = 0.945, 0.869; Kg = 17.2 +/- 1.6, 15.5 +/- 1.9%/day; Yoshida and Novikoff, respectively). The fractional degradation rate of tumor protein (Kd) was determined as the difference between the two first order rate constants Ks and Kg. The tumor protein degradation rate was significantly reduced in the Yoshida tumors compared to the Novikoff tumors (19.6 +/- 8.2% versus 39.6 +/- 4.2%/day, respectively). The greater size in the Yoshida sarcoma can be attributed to reduction in fractional protein degradation rather than change in synthesis rates, which supports the theory that some tumors can regulate their growth by alteration in tumor protein degradation rates (J. A. Tayek et al., Cancer Res., 46:5649-5654, 1986). PMID- 3345529 TI - Reversal of transformed phenotypes by herbimycin A in src oncogene expressed rat fibroblasts. AB - We studied the effectiveness of herbimycin A, an inhibitor of the function of the src oncogene, to reverse the various transformed phenotypes in normal rat kidney (NRK) cells integrating temperature-sensitive v-src (ts/NRK). Elevated glucose transport in ts/NRK cells at a permissive temperature (33 degrees C) was decreased by herbimycin in 8 h to near the level that was observed either in ts/NRK grown at a nonpermissive temperature (39 degrees C) or in untransformed NRK cells at either temperature. Herbimycin caused no significant decrease in glucose uptake in ts/NRK cells grown at 39 degrees C. The effects of herbimycin on serum- and anchorage-independent growth properties of ts/NRK cells and of NRK cells integrating K-ras (KNRK) were also examined. With ts/NRK cells grown at 33 degrees C, the inhibition of cell growth by herbimycin became more pronounced when the serum concentration in the medium was lowered. With KNRK cells, in contrast, almost the same extent of cell growth inhibition was exerted by herbimycin irrespective of the serum concentration. Furthermore, with ts/NRK cells grown at 33 degrees C, herbimycin inhibited the colony formation in the soft agar medium more strongly than on a solid support. No such differential effects were observed with KNRK cells under similar conditions. These results suggest that herbimycin specifically acts on cells expressing the src oncogene and reverses various transformed characteristics to the normal ones. PMID- 3345530 TI - Effect of cimetidine on inhibition by tetragastrin of carcinogenesis induced by N methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. AB - The effects of combined administration of cimetidine and tetragastrin on gastric acid secretion, the labeling index of the gastric mucosa, and the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin in depot form after treatment with N-methyl-N'-nitro-N-nitrosoguanidine resulted in a significant increase in gastric acid secretion, a significant decrease in the labeling index of the antral mucosa, and a significant decrease in the incidence of adenocarcinomas of the glandular stomach. Administration of cimetidine at 20 mg, but not 10 mg, per kg body weight with tetragastrin significantly reduced the gastric acid secretion induced by tetragastrin alone but did not influence the labeling index of the antral mucosa or the inhibitory effect of tetragastrin on gastric carcinogenesis. These findings indicate that gastric acid secretion has no influence on the development of gastric adenocarcinomas and that the inhibitory effect of tetragastrin on gastric carcinogenesis may be related to its effect in decreasing proliferation of cells in the antral mucosa. PMID- 3345532 TI - Reduction of potential for replicative but not unscheduled DNA synthesis in hepatocytes isolated from aged as compared to young rats. AB - Replicative DNA synthesis of hepatocytes obtained from 2- to 3-month-old and 28- to 30-month-old rats was examined in primary culture under serum-free conditions to clarify whether observed age-related changes in DNA replication depend exclusively on intracellular events, or whether humoral factors are involved. Hepatocyte replicative DNA synthesis of the aged rats was significantly lower (less than one tenth, P less than 0.001) than that of 2- to 3-month-old rats. EGF receptor assays, however, revealed no difference in either number or affinity of the cell surface receptors between hepatocytes from aged as opposed to young rats. Furthermore, sera obtained from aged rats did not demonstrate any inhibitory effect on DNA synthesis of young rat hepatocytes. After treatment with N-hydroxy acetylaminofluorene, N-nitroso-N-methylurea, or 254-nm UV irradiation degree of resultant UDS was similar in hepatocytes from both young and aged animals. Thus, while the results suggest that potential for DNA replication markedly diminishes with age, DNA repair systems are well preserved. PMID- 3345531 TI - DNA methylation and expression of the rat pepsinogen gene in embryonic, adult, and neoplastic tissues. AB - The relationship between methylation and expression of rat pepsinogen 1 (Pg1) genes was investigated in various tissues. On Northern blotting with a Pg1 complementary DNA probe, Pg1 mRNA was detected only in the glandular stomach of normal rats. Methylation analysis with Msp1/HpaII and Hha1 revealed tissue specific methylation patterns of Pg1 genes with less methylated in the stomach than in other normal tissues not expressing the genes. During stomach development, there was a progressive increase in the Pg1 mRNA level that almost coincided with change in the mucosal pepsinogen level and progressive demethylation after the onset of transcription. Thus, there was an inverse correlation between methylation and expression of Pg1 genes, suggesting a role of DNA methylation in Pg1 gene regulation during normal differentiation, although not its primary role in gene activation. There was no detectable Pg1 mRNA in either primary or transplanted stomach cancers induced by N-methyl-N'-nitro-N nitrosoguanidine. The methylation patterns of Pg1 genes were different from those of normal tissues that expressed the gene and of those that did not and no simple correlation was observed between methylation and expression of Pg1 genes. This result is consistent with a previous finding that DNA methylation is deranged in tumor cells. PMID- 3345533 TI - A case-control study of past history of nasal diseases and maxillary sinus cancer in Hokkaido, Japan. AB - A case-control study of maxillary sinus cancer was performed in Hokkaido with 116 cases and 232 controls matched for sex, age (within 5 years), and residence (same health center region). Preliminary univariate analyses showed that a history of chronic sinusitis [relative risk (RR) = 3.1]; nasal polyps (RR = 5.7); an occupational history of being a carpenter, joiner, furniture maker, or other woodworker (RR = 2.9); and a history of current or past cigarette smoking (RR = 3.3) were statistically significant risk factors for men. No single item was a significant risk factor for women. PMID- 3345534 TI - Adult stature and risk of cancer. AB - We examined the relationship between adult stature and cancer incidence using data from the first U.S. National Health and Nutrition Examination Survey and its follow-up study. Among 12,554 participants 25-74 years old, 460 cancers occurred in men and 399 in women after an average follow-up period of approximately 10 years. The age-adjusted relative risk of cancer for the second (Q2) through fourth (Q4) quartiles of stature compared to the first quartile among men were significantly increased: 1.5, 1.4, and 1.4. After adjustment for race, cigarette smoking, income, and body mass index, the all-sites cancer relative risk increased slightly to 1.6, 1.5, and 1.6. For most cancer sites in men, and particularly colorectal cancer (relative risk = 2.1 for Q4), the lowest incidence was observed among those in the shortest quartile of stature. A weaker, positive association was evident among women, restricted primarily to cancer of the breast and colorectum (relative risk in Q4 = 2.1 and 1.6 for the two cancers, respectively). These findings indicate that short stature is associated with reduced risk of cancer, particularly in men, and suggest a role for nutrition early in life in human carcinogenesis. PMID- 3345535 TI - Circadian rhythm-varying plasma concentration of 5-fluorouracil during a five-day continuous venous infusion at a constant rate in cancer patients. AB - A circadian rhythm in the plasma concentration of 5-fluorouracil (5-FUra) is demonstrated in seven patients receiving this drug as a continuous venous infusion at a constant rate for 5 days. All patients had stage C bladder carcinoma and received cis-diamminedichloroplatinum(II) (45-91 mg/m2) on day 1 as a 30-min venous infusion at 5 p.m. Continuous venous infusion of 5-FUra (450-966 mg/m2/day) was started on day 2 at 8:30 a.m. via a volumetric pump and lasted for 5 days (until day 6). Blood samples were obtained on EDTA every 3 h on days 2, 4, and 6 on each patient (20 samples/patient). 5-FUra plasma concentration was determined by high performance liquid chromatography. Data were analyzed by both multiple analysis of variance and cosinor. Mean lowest and highest values (+/- SEM) were, respectively, 254 +/- 33 ng/ml at 1 p.m. and 584 +/- 160 ng/ml at 1 a.m. (F = 2.3; P less than 0.03). Because of large intersubject differences in 24 h mean plasma concentration, data were also expressed as percentages of each patient's 24-h mean. Both analysis of variance and cosinor analysis further validated (P less than 0.0001) a circadian rhythm with a double amplitude (total extent of variation) of 50% of the 24-h mean and an acrophase located at approximately 1 a.m. (estimated time of peak). Such findings warrant a thorough scrutiny at the chronopharmacology of anticancer drugs when designing continuous infusion schedule. A circadian modulation of the infusion rate of this drug may further optimize the therapeutic index of such treatment modality. PMID- 3345536 TI - Growth potential of human colorectal carcinomas in nude mice: association with the preoperative serum concentration of carcinoembryonic antigen in patients. AB - A preoperative serum carcinoembryonic antigen (CEA) concentration greater than 5 ng/ml portends a poor prognosis for patients with colorectal carcinoma. The purpose of this study was to determine if the tumorigenicity of colorectal carcinomas in nude mice was associated with the preoperative serum CEA concentration. Neoplasms from 53 patients were either implanted as fragments or dissociated with collagenase and DNase, and 3 x 10(6) viable cells were injected into the flanks of BALB/c nude mice. The growth potential of tumors resected from patients with CEA levels exceeding 5 ng/ml was greater than that of tumors from patients with normal serum CEA: 26 of 33 carcinomas from patients with CEA greater than or equal to 5 ng/ml were tumorigenic in nude mice, whereas only 8 of 22 neoplasms from patients with normal serum CEA were tumorigenic in nude mice (P less than 0.001). Primary colorectal cancers, not metastases, were the basis for the association between tumorigenicity and preoperative CEA. Tumorigenicity was also associated with stage of disease, since Dukes' D primary tumors and metastases were more tumorigenic than Dukes' A to C primary tumors. Growth in nude mice was not associated with other prognostic factors such as tumor site, mucin production, local invasion, or stage of histological differentiation. The tumorigenic capability of human colorectal carcinomas may be associated with the preoperative serum CEA concentration and may reflect an increased potential to develop clinical metastases. PMID- 3345537 TI - Modification of regression of virally xenogenized tumor cells by cyclophosphamide and busulfan. AB - Rat fibrosarcoma cells infected with Friend leukemia virus (FV-KMT-17) grow for a short time and then regress spontaneously in syngeneic hosts. This regression mechanism was examined by analyzing the immunomodulating action of the antitumor drugs busulfan (BU) and cyclophosphamide (CY). In preliminary experiments, the optimum dosages of BU and CY for the enhancement of DTH responses to SRBC were 10 mg/kg and 40 mg/kg respectively. Treatment of rats with BU (10 mg/kg) on day 5 induced the regression of KMT-17 cells, while in contrast, the same drug delayed the spontaneous regression of FV-KMT-17 cells. Pretreatment with CY (40 mg/kg) on day 5 did not affect the growth of KMT-17 or FV-KMT-17 cells. After the same treatment schedule, BU inhibited humoral antibody formation against SRBC and against virus-associated antigen (VAA), NK cell activity, and ADCC effector cell activity. On the other hand, CY did not affect the activities of NK cells or ADCC effector cells, although it significantly augmented the DTH responses to SRBC and the production of antibody to VAA but had no effect on production of antibodies to SRBC. These results suggest that NK cells and ADCC may play an important role in the initial stage of the spontaneous regression of FV-KMT-17 cells. PMID- 3345538 TI - Lack of suppressive activity of human primary melanoma cells on the activation of autologous lymphocytes. AB - Previous studies have indicated that primary but not metastatic melanomas were able to stimulate the proliferation of autologous (Auto) peripheral blood lymphocytes (PBL) in 73% of cases. On the other hand, 57% of the metastatic melanomas were shown to be suppressive when melanoma cells (Me) were admixed with Auto-PBL stimulated with allogeneic (Allo) PBL or interleukin 2 (IL-2) at the beginning of a 6-day incubation period. Here, we report that the suppressive activity of Me is a functional characteristic associated with a particular stage of the disease. In fact, we found that none of the 11 primary tumors tested were able to inhibit the proliferative response of Auto-PBL to Allo-PBL or IL-2 at all the doses of tumor cells used. The generation of lymphocytes cytotoxic against Auto-Me or K562 was also not inhibited. Of the 11 primary tumors checked for suppression, 8 were able to stimulate Auto-PBL in a primary mixed lymphocyte tumor culture. We conclude that opposite functions, stimulation and inhibition of autologous lymphocyte responses are characteristics of primary and metastatic Me, respectively. PMID- 3345539 TI - Human corpus luteum: immunocytochemical evidence for presence of prolactin. AB - Six human corpora lutea (day 17-25) of the menstrual cycle and 4 ovarian stromal tissues from 7 cycling women were examined for the presence of the hormone, prolactin, by immunohistochemistry using the indirect peroxidase-antiperoxidase method. After mounting tissue sections of 4 micron, endogenous peroxidases were removed with hydrogen peroxide and the sections were incubated for 1 h at room temperature followed by 16 h at 4 degrees C with a highly specific antisera for human prolactin, nonimmunized normal rabbit serum for a control reaction, or antiserum preadsorbed with excess human prolactin for specificity determination. Following the reaction with the second antibody (goat antirabbit IgG) for 1 h at room temperature, prolactin was localized using peroxidase anti-peroxidase and 3.3'-diaminobenzidine as the chromogen. Prolactin was present and could be localized in the luteal cells of all 6 corpora lutea, but not in any of the ovarian stroma studied. Human adenohypophysis served as a positive tissue control for prolactin immunopositive staining. The localization of immunoreactive prolactin in the corpus luteum demonstrates directly the presence of this hormone in the human ovary, adding further evidence for its role in luteal function. PMID- 3345541 TI - Morphology of smooth muscle cells in the rat thoracic duct. A scanning and transmission electron-microscope study. AB - The three-dimensional cytoarchitecture and ultrastructure of the smooth muscle cells in the wall of the rat thoracic duct were investigated by scanning and transmission electron microscopy. The muscle layer basically consists of a single layer of circularly arranged cells. The smooth muscle cell is fusiform or ribbon like in shape, as in veins or venules with a similar or smaller diameter. Connections by spinous processes are observed between adjacent muscle cells along their length. Spot-like membrane contacts frequently occur in areas where facing membranes are closely apposed. These are thought to be gap junctions and may be responsible for electrical coupling and mechanical attachment. Large invaginations arranged regularly in rows on the surface of the smooth muscle cells can be observed. These invaginations are closely associated with a flattened sarcoplasmic reticulum, and caveolae tend to open into the invaginations. PMID- 3345540 TI - Single modified cilia displayed by cells of human internal stratified epithelia (oral cavity, vagina). AB - Serial sections of human vaginal and keratinized oral-gingival epithelia were investigated for ciliary structures. Most melanocytes of the gingival epithelium lacked cilia, whereas almost all basal keratinocytes of the deeper portion of the epithelial ridges possessed one cilium each. In the suprabasal layers of the ridges only a few keratinocytes exhibited a single cilium. In the basal layer, at the top of the connective tissue papillae, approximately every second keratinocyte displayed a single cilium. In the suprabasal layers above the ridges no ciliated keratinocytes were observed. The basal cells of the vaginal epithelium were endowed with cilia, while cilia were absent from the suprabasal cells. In the human forearm epidermis most melanocytes and keratinocytes are supplied with a single cilium; it has been suggested that they may play a role in light reception. However, the widespread occurrence of 9 + 0 cilia in epithelial cells of internal epithelia and their coincidence with the sites of renewal of keratinocytes suggests that a relationship may exist between solitary cilia and mitotic activity. PMID- 3345542 TI - Fine-structural and immunohistochemical study of anterior pituitary cells of Snell dwarf mice. AB - Snell dwarf mice display remarkable retardation of growth after birth and are known to lack prolactin (PRL), thyroid stimulating hormone (TSH) and growth hormone (GH). The aim of this study was to determine the reason for these hormonal deficiencies. We examined the fine structure of the gland and its immunohistochemical staining pattern with respect to antisera raised against PRL, TSH, GH, adrenocorticotrophic hormone (ACTH) and luteinizing hormone (LH). The gland of control mice reacted immunohistochemically against all antisera used, whereas only ACTH-producing cells (ACTH cells) and LH-producing cells (LH cells) were distinguished in the dwarf mice. ACTH cells in dwarf mice varied in cell shape, although they were similar in size to those of controls. The distribution of secretory granules in the cytoplasm varied from cell to cell. LH cells in the dwarf mice showed immature features, having poorly developed rough endoplasmic reticulum and Golgi apparatus. The cells were about half the size of controls, and secretory granules were smaller. In dwarf mice, non-granulated cells were encountered in addition to granulated ACTH and LH cells. Some of them formed small clusters, characteristic cell junctions being found between the cells; they thus appeared to be follicular cells. The above results suggest that hormone deficiency in Snell dwarf mice is a result of a defect in the hormone-producing cells in the gland. PMID- 3345543 TI - Pathway of nerves with vasoactive intestinal polypeptide-like immunoreactivity to the major cerebral arteries of the rat. AB - The pathway of nerves with vasoactive intestinal polypeptide (VIP)-like immunoreactivity to the major cerebral arteries was studied in rats by means of the indirect immunofluorescent method. The fibers are densely distributed in the ethmoidal nerves and in the adventitia of both the external and internal ethmoidal arteries. Section of both ethmoidal nerves and external ethmoidal arteries before they enter the cranial cavity induced a marked reduction of VIP like immunoreactive fibers in the walls of the vessels of the circle of Willis and its major branches. However, section of the external ethmoidal artery alone did not result in visible changes of the nerves around major cerebral arteries. The present study suggests that VIP-like immunoreactive fibers surrounding major cerebral arteries of the rat arise from fibers in the ethmoidal nerve showing immunoreactivity to VIP. PMID- 3345544 TI - Immunocytochemical studies on the pituitary pars distalis of the Japanese long fingered bat, Miniopterus schreibersii fuliginosus. AB - Immunocytochemical studies were performed to describe the characteristics of cell types and their distribution in the pars distalis of Japanese long-fingered bat, Miniopterus schreibersii fuliginosus, collected at various stages of the reproductive cycle. Six distinct cell types have been identified in the pars distalis by the unlabeled immunoperoxidase technique and by the ABC method. Growth hormone (GH) and prolactin (PRL) cells were immunostained with antisera against chicken GH and ovine PRL. The GH-immunoreactive cells were round or oval orangeophilic cells distributed throughout the pars distalis with prominent aggregation in the posterolateral region. The PRL cells were pleomorphic carminophilic cells that occurred in small groups within the central and dorsocaudal regions of the pars distalis. They were sparsely distributed in the central region of the pars distalis in the hibernating bats, but increased significantly in the pregnant and lactating bats. The adrenocorticotropic (ACTH) cells were large round or polygonal amphophilic cells in the rostroventral and ventrolateral regions of the pars distalis. The thyrotropic (TSH) cells were small rounded or polygonal and distributed mainly in the ventrolateral region of the pars distalis. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) cells were identified immunocytochemically with antisera against the specific beta subunits of ovine LH and rat FSH. There were two populations of LH and FSH cells, one aggregated in the zona tuberalis and the other scattered singly throughout the rest of the pars distalis. The aggregated cells were immunoreactive with both antisera directed to LH and FSH, while scattered cells were reactive solely with antiserum to either LH beta or FSH and exhibited seasonal variations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345545 TI - Ultrastructural localization of peanut lectin binding to extravascular white blood cells in the bone marrow of embryonic chicks. AB - Labelling by the galactose-specific lectin peanut agglutinin was studied in bone marrow of the embryonic chick at the electron-microscopic level by use of both a gold-conjugated lectin and an indirect, ferritin-conjugated, biotinylated lectin. Cell surface labelling is exclusively restricted to developing and mature heterophilic granulocytes, monocyte/macrophages, mast cells/basophils, all of which appear to develop and reside in the extravascular spaces of the bone marrow. Resident small lymphocytes, which comprise a minor portion of the cell population, are also labelled. Erythroid cells and thrombocytic cells, which develop inside venous sinusoidal vessels, display no labelling. The latter cells, like extravascular leukocytes, contain surface galactosyl residues located in subterminal positions on cell surfaces, since they are labelled by the galactose specific Ricinus communis agglutinin-I. It is postulated that terminal galactosyl residues might be involved in interactions between the surfaces of extravascular leukocytes and extracellular matrix and/or stromal cell surfaces. PMID- 3345546 TI - Lysozyme localization in human gastric and duodenal epithelium. An immunocytochemical study. AB - The distribution of lysozyme in normal gastric and duodenal mucosa was studied by light- and electron-microscopic immunocytochemical techniques (direct enzyme labeled antibody method). In the duodenal mucosa, lysozyme was found in the Paneth cells and the epithelial cells of Brunner's glands. Electron microscopically, lysozyme was found in rough endoplasmic reticulum and perinuclear spaces, which were assumed to be protein-synthesizing organelles, and also in the secretory granules of Paneth cells. Additionally, lysozyme was detected in the stomach in mucinous granules and in some parts of the rough endoplasmic reticulum within the epithelial cells of the pyloric glands, the mucous neck cells of the fundic glands, and in several surface epithelial cells of the plyoric and fundic regions. This suggests that some quantity of lysozyme in gastrointestinal secretion originates from the gastric and duodenal glands, and that it acts as a defense mechanism in the gastrointestinal tract. PMID- 3345548 TI - Cell recruitment during glial repair: the role of exogenous cells. AB - Selective disruption of the neuroglia in penultimate abdominal connectives of the cockroach nerve is followed by a rapid accumulation of cells in the perineurial layer of the lesion. Subsequently, there is an abrupt, secondary, rise in cell numbers in the undamaged perineurial tissues, anterior to the lesion and adjacent to the 4th abdominal ganglia. By 7 days the increased cell numbers are again effectively confined to the original lesion zone. The initial rise in cell numbers is postulated to result from an invasion by blood-borne haemocytes and the subsequent increase, in undamaged perineurial tissues, from the mobilization of endogenous reactive cells. Recruitment of the endogenous cells is inhibited if the haemocytes are excluded from the lesion. There is a slower mobilization of sub-perineurial cells, which, again, is inhibited following exclusion of haemocytes from the lesion zone. It is postulated that the recruitment of the endogenous reactive cells is initiated by the invading haemocytes which transform to granule-containing cells and release diffusible morphogenic and/or mitogenic factors. PMID- 3345547 TI - Carbohydrate moieties of the basal lamina: their role in attachment and spreading of basal corneal epithelial cells. AB - Three lectins, Wheat germ agglutinin, succinyl Concanavalin A and Ricinus communis agglutinin were used to block specific sugar moieties in the basal lamina. Corneal epithelial basal cells were plated onto freshly denuded basal lamina. Attachment was studied by quantifying the adherence of prelabeled cells and by examining attachment sites using transmission electron microscopy. Spreading was examined using scanning electron microscopy. Attachment of the cells occurred within 15 min and spreading was apparent after 45 min. Both Wheat germ agglutinin and beta-N-acetylglucosaminidase inhibited cellular attachment. Succinyl Concanavalin A and Ricinus Communis agglutinin permitted attachment, but inhibited extensive cellular spreading. The results indicate that the attachment of basal cells is dependent on N-acetylglucosamine residues, and spreading is mediated by alpha methylmannoside, glucose, and galactose residues. PMID- 3345550 TI - Immuno-electron-microscopic study of the prolactin cells in the pituitary gland of male Wistar rats during aging. AB - Prolactin cells were identified by means of immunocytochemistry with protein-A gold as a marker on ultrathin sections of the pituitary gland of young (3-4 months), middle-aged (16-19 months), and aged (26-30 months) male Wistar rats. Point-counting volumetry revealed that the prolactin (PRL) cell-volume density in middle-aged rats was significantly increased in comparison to the volume densities in young and aged rats. Within the PRL-cell population, four types of PRL cells were distinguished on the basis of the shape and size of their secretory granules. During aging, dramatic changes occurred in the relative volumes of the four cell types. The volume percentage of cells with round granules (type I, granule diameter 150-250 nm, and type IIA, granule diameter 250 350 nm) increased from +/- 30% in young rats to +/- 90% in old rats. The volume percentage of cells with round and polymorphic granules (type IIB; granule diameter 350-400 nm and type III; granule diameter 500-600 nm) decreased from +/- 70% in young rats to +/- 7% in old rats. Age-related changes in serum PRL levels were not found. It is concluded that although during the life span of the male Wistar rat considerable changes in PRL-cell volume densities and in the ratios of PRL-cell types occur serum, PRL levels remain more or less constant. PMID- 3345549 TI - Distribution and origin of vasoactive intestinal polypeptide (VIP) immunoreactive, acetylcholinesterase-positive and adrenergic nerves of the cerebral arteries in the bent-winged bat (Mammalia: Chiroptera). AB - The overall distribution and origins of vasoactive intestinal polypeptide (VIP) immunoreactive (IR), acetylcholinesterase (AChE)-positive and adrenergic nerves in the walls of the cerebral arteries were investigated in the bent-winged bat. VIP-IR and AChE-positive nerves innervating the bat cerebral vasculature appear to arise mainly from VIP-IR and AChE-positive cell bodies within microganglia found in the nerve bundle accompanying the sympathetic nerve bundle within the tympanic cavity. These microganglia, as well as the nerve bundle containing them, do not emit catecholamine fluorescence, suggesting that they are of the cranial parasympathetic outflow, probably the facial or glossopharyngeal one. The axons from VIP-IR and AChE-positive microganglia run intermingled with sympathetic adrenergic nerves in the same thick fiber bundles, and reach the cranial cavity through the carotid canal. In addition, some of the VIP-IR fibers innervating the vertebro-basilar system, at least the basilar artery, originate from VIP-IR nerve cells located in the wall of this artery. The supply of VIP-IR fibers to the bat major cerebral arteries is the richest among mammals in that it is much greater in the vertebro-basilar system than in the internal carotid system: plexuses of VIP-IR nerves are particularly dense along the walls from the posterior ramus to posterior cerebral and basilar arteries. Small pial and intracerebral arteries of the vertebro-basilar system, especially those of the posterior cerebral artery which supply most parts of the diencephalon and cerebrum, are also richly innervated by peripheral VIP-IR fibers. This pattern corresponds well with the innervation pattern of adrenergic and AChE-positive nerves. PMID- 3345551 TI - Quantitation and localization of acinar cell-specific mucin in submandibular glands of mice during postnatal development. AB - In this study, antiserum to acinar cell-specific mucin was utilized to determine whether mucin could be detected in the mouse submandibular gland prior to cytodifferentiation of acinar cells. Results from radioimmunoassay indicated that mucin occurs in submandibular glands from newborn mice, i.e., before the appearance of mature acinar cells. Additionally, mucin quantitated in various stages of development was found to be antigenically identical to adult mucin. After sections of glands were treated with immunohistochemical reagents, we observed that the mature acinar cell-specific mucin was present in secretory terminal-tubule cells and in proacinar cells of newborn animals. The present findings suggest that in young animals, the proacinar cells are an immediate precursor of acinar cells and that the secretory terminal-tubule cells may represent an earlier stage in development of acinar cells. In adult female glands, mucin was also detected in the granular intercalating-duct cells. This latter observation is consistent with the hypothesis that these cells are an intermediate in the acinar cell replacement process. PMID- 3345552 TI - Mapping of enkephalin-related peptides in the nervous system of the blowfly, Calliphora vomitoria, and their co-localization with cholecystokinin (CCK)- and pancreatic polypeptide (PP)-like peptides. AB - The distribution of enkephalin-like immunoreactive material has been studied in the CNS of C. vomitoria. The presence of both Met- and Leu-enkephalin-related peptides is suggested by differential immunostaining with a variety of antisera. Comparisons made between certain of the enkephalin-immunoreactive perikarya, nerve fibres and terminals with cells in corresponding positions as evidenced in previously published neuroanatomical studies of the dipteran brain have suggested specific enkephalinergic pathways. As examples, one Met-enkephalin-immunoreactive neuron appears to link the lobula with the dorsal protocerebrum, and a group of Leu-enkephalin cells in the pars intercerebralis appear to have arborisations in both the central body (fan-shaped body) and the tritocerebral neuropil around the oesophageal foramen. Neuronal pathways of this type indicate that the enkephalin like peptides of the fly brain are functioning as neurotransmitters and/or neuromodulators. In the thoracic ganglia, symmetrically arranged cells, immunoreactive to both Met- and Leu-enkephalin antisera, are positioned ventrally in pairs on either side of the mid-line in a sagittal plane. Very little immunoreactive material is observed in the neuropil, however, and the source of the accumulation of Leu-enkephalin-immunoreactivity in the dorsal neural sheath is not certain. It is suggested that this material, in contrast to that present in areas of the brain, acts as a neurohormone and that it may have a physiological role following its release into the haemolymph. The enkephalin-like immunoreactive material of certain neurons identified within the brain and thoracic ganglion shows a complex pattern of co-existence with pancreatic polypeptide- and gastrin/cholecystokinin-like peptides. PMID- 3345553 TI - Interaction of plasma proteins with negatively charged sites on the pulmonary capillary endothelium of the rat. AB - The endothelial glycocalyx, a polyanionic structure which may regulate the passage of solutes and water through the endothelium, readily binds cationic ferritin (CF). In normal, nonexchange-transfused rats, however, only 7.5% and 6.0% of the luminal plasma membrane and 7.5% and 5.0% of vesicle diaphragms on the thick and thin side of pulmonary capillaries, respectively, bound cationic ferritin. With the graded removal of circulating proteins by exchange transfusion with fluorocarbon emulsion, up to 89 and 82% of the luminal surface, and 76 and 73% of vesicle diaphragms on the thick and thin sides, respectively, bound CF. Although the extent of binding on the thin side was consistently less than on the thick side, the difference was not statistically significant. The extensive binding of CF to the glycocalyx in totally exchange-transfused rats was completely reversible upon addition of lyophilized rat serum protein to the perfusate. These data suggest that in vivo anionic sites of the endothelial glycocalyx are partially masked by adsorbed plasma proteins. PMID- 3345554 TI - Structural studies of nerve terminals containing melanin-concentrating hormone in the eel, Anguilla anguilla. AB - Eels were adapted to black- or white-coloured backgrounds and the pituitary glands were prepared for light and electron microscopy. Immunocytochemical staining was used to study the distribution of the neurohypophysial melanin concentrating hormone in the neurointermediate lobe. The hormone was located in small, elliptical, electron-opaque neurosecretory granules, measuring approximately 120 x 90 nm. The neurones terminated on blood vessels in the centre of the neurohypophysis and on the basement membrane separating neural and intermediate lobe tissues. The results of both light and electron immunocytochemistry and of radioimmunoassay are consistent with a higher rate of hormone release from eels adapted to white backgrounds than from those adapted to black backgrounds. In addition to this, when fish that had been adapted to white tanks were transferred to black tanks, there was an accumulation of irMCH in the gland and an increased numerical density of secretory granules at nerve terminals. These results reinforce the proposal that MCH is released during adaptation to a white background, to cause melanin concentration and to inhibit MSH release, and that its release is halted in black-adapted fish. PMID- 3345555 TI - Adaptation of intestinal morphology in the temperature-acclimated carp, Cyprinus carpio L. AB - The effects of temperature and photoperiod acclimation upon the morphology of carp intestinal mucosa have been studied using morphometric techniques. Carp intestine showed an absence of anatomical regionalisation. There was a gradual reduction in the dimensions of villi along the tract. The decrease in the dimensions of the villi was greatest in the anterior half. Temperature acclimation had no effect on intestinal-somatic indices. Acclimation to 10 degrees C or 30 degrees C resulted in large differences in the dimensions of villi. Cold acclimation produced significant increases in mean villus height and breadth along the entire intestine. These villus shape changes resulted in a 58% increase in total mucosal surface area and a 102% increase in total volume of villi in cold-acclimated fish relative to warm-acclimated fish. Surface area of the unmodified intestinal tube increased with cold acclimation by 28%. The total number of villi remained unchanged by thermal acclimation. Because normalisation to a nominal surface area does not take account of the possibility of differentially developed mucosal surfaces in differently acclimated animals, experiments comparing transepithelial transport rates of differently-acclimated fish, using unstripped preparations, overestimates the differences in area specific transport capacity. PMID- 3345556 TI - Interference with function of plasmatocytes of Heliothis virescens in vivo by calyx fluid of the parasitoid Campoletis sonorensis. AB - Immature stages of the ichneumonid parasitoid, Campoletis sonorensis, develop within the haemocoel of its noctuid host, Heliothis virescens. The host cannot encapsulate the parasitoid egg owing to the suppressive effect of the polydnavirus-laden calyx fluid injected by the female parasitoid during oviposition. We have examined the effects of injection of calyx fluid on the following haemocytic manifestations of the immune system of 5th-instar larvae of H. virescens: encapsulation, nodulation, phagocytosis, erythrocyte rosetting and coagulation. Of these phenomena, only those requiring the formation of a multicellular sheath of plasmatocytes were affected. In general, encapsulation was fully suppressed; all of the C. sonorensis eggs and most of the glass rods implanted as targets were devoid of attached haemocytes 3 days after implantation although a few of the latter were coated by a sparsely distributed layer of granulocytes. Plasmatocytes also appeared to be present in thicker depositions of haemocytes. In nodulation, only the second, encapsulation-like phase was inhibited. The resistant first stage, involving the entrapment of particles by haemocytes, only resulted in the formation of amorphous, disorganized nodules. Granulocyte-dependent aspects of the immune system (phagocytosis, rosetting and possibly coagulation and the first stage of encapsulation and nodulation) occurred normally. The data suggest that in 5th-instar hosts injection of calyx fluid acts specifically on plasmatocyte function. PMID- 3345557 TI - Localization of ovulation hormone-like neuropeptide in the central nervous system of the snail Lymnaea stagnalis by means of immunocytochemistry and in situ hybridization. AB - The caudo-dorsal cells (CDC) in the cerebral ganglia of the pond snail Lymnaea stagnalis synthesize the 36-amino acid ovulation hormone (CDCH). We have used immuno-cytochemistry and in situ hybridization to reveal the localization of neurons and axons containing CDCH-like material. A monoclonal antibody to a fragment of CDCH and a cDNA probe encoding CDCH reacted with the CDC-system, with specific cell groups in the cerebral and pleural ganglia, and with individually occurring neurons throughout the central nervous system. The cells in the pleural ganglia, which were found in about 50% of the preparations studied, are considered as "ectopic" CDC. They are morphologically similar to CDC in their somal dimensions and axonal organization. By means of immuno-electron microscopy it was shown that these neurons contain secretory vesicles that are similar to those of the CDC. The neurons of the bilateral groups occurring in the cerebral ganglia in addition to the CDC are smaller and more intensely stained than the CDC. Axons of these small neurons probably have varicosities located on the CDC axons in the neuropil of the cerebral ganglion, indicating synaptic contacts. Two major axon tracts could be followed from (or toward) the neuropil of the cerebral ganglion. One tract runs from the cerebral ganglion via the pleural and parietal ganglia to the visceral ganglion, giving off branches to most nerves emanating from these ganglia. The other tract could be traced through the cerebro-pedal connective to the pedal ganglia. Only in the right pedal ganglion was extensive axonal branching observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345558 TI - Embryonic lethalities and endothelial tumors in chimeric mice expressing polyoma virus middle T oncogene. AB - The effect of the middle T oncogene of polyoma virus was studied in vivo using a replication-defective selectable retrovirus. Injection of virus into newborn and adult mice resulted in the rapid appearance of cavernous hemangiomas. Infection of embryos did not yield transgenic mice; therefore, embryonal stem (ES) cells were used as an alternative system. Several infected ES cell clones were established that constitutively expressed middle T and its associated tyrosine kinase activity. Chimeric embryos obtained by blastocyst injection of individual ES cell clones were specifically arrested at midgestation, when multiple hemangiomas disrupted blood vessel formation. From these tumors endothelial cell lines were established that retained expression of von Willebrand factor yet were tumorigenic in vivo. These results suggest that middle T acts in endothelial cells as a single-step oncogene and that ES cells provide a valuable system for the study of growth control during embryogenesis. PMID- 3345559 TI - Molecular genetics of the single-minded locus: a gene involved in the development of the Drosophila nervous system. AB - The embryonic neuroepithelium of Drosophila gives rise to the central nervous system. We have studied the mutant phenotype and expression of a gene, single minded (sim), which is involved in generating a specific region of this neuroepithelium. In sim mutant embryos, a subset of neuronal and nonneuronal precursor cells lying along the midline fail to emerge with the rest of the neuroepithelium. We have identified the sim transcription unit and have shown by in situ hybridization to embryos that the sim gene is expressed specifically in the midline neuroepithelium. Both the mutant phenotype and the temporal and spatial expression of transcripts suggest that the sim gene plays a key role in the emergence of this subset of cells along the midline of the developing central nervous system. PMID- 3345560 TI - The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product. AB - Mutations in the single-minded (sim) gene of Drosophila result in the loss of the precursor cells giving rise to the midline cells of the embryonic central nervous system. We have examined the structure of the sim product by sequencing a sim cDNA clone, and have also determined the subcellular localization of the protein and its developmental expression by staining embryos with an antiserum against a sim fusion protein. The results indicate that sim is a nuclear protein specifically expressed along the midline of the neuroepithelium, the same subset of cells that are missing in the mutant. No similarity is observed between sim and any known nuclear protein, but, surprisingly, it is similar to the Drosophila period (per) locus gene product, which controls the periodicity of biological rhythms. PMID- 3345561 TI - Two distinct subpopulations of endosomes involved in membrane recycling and transport to lysosomes. AB - Functionally distinct subpopulations of endosomes involved in targeting internalized material to specific intracellular destinations were resolved as two distinct peaks by free-flow electrophoresis. The less anodally shifted peak contained a population of early endosomes selectively labeled by brief exposures to endocytic tracers or by receptor-bound transferrin. Late endosomes, labeled only after longer periods of internalization, migrated more toward the anode. While both fluid phase and certain receptor-bound markers could be rapidly chased from early to late endosomes, transferrin remained in vesicles comigrating with early endosomes even after prolonged uptake. Thus early and late endosomes are kinetically related but functionally distinct: early endosomes serve as the major site of recycling of membrane and surface receptors and late endosomes are involved in delivery to lysosomes. The subpopulations each contain unique polypeptides not found on the plasma membrane. Thus, endosomes cannot be derived entirely from internalized cell surface components, and may have at least partly independent biosynthetic origins. PMID- 3345562 TI - Identification of genes required for cytoplasmic localization in early C. elegans embryos. AB - We have isolated and analyzed eight strict maternal effect mutations identifying four genes, par-1, par-2, par-3, and par-4, required for cytoplasmic localization in early embryos of the nematode C. elegans. Mutations in these genes lead to defects in cleavage patterns, timing of cleavages, and localization of germ line specific P granules. Four mutations in par-1 and par-4 are fully expressed maternal effect lethal mutations; all embryos from mothers homozygous for these mutations arrest as amorphous masses of differentiated cells but are specifically lacking intestinal cells. Four mutations in par-2, par-3, and par-4 are incompletely expressed maternal effect lethal mutations and are also grandchildless; some embryos from homozygous mothers survive and grow to become infertile adults due to absence of functional germ cells. We propose that all of these defects result from the failure of a maternally encoded system for intracellular localization in early embryos. PMID- 3345563 TI - Overproduction of protein kinase C causes disordered growth control in rat fibroblasts. AB - We have generated a series of rat fibroblast cell lines that stably overexpress a full-length cDNA encoding the beta 1 form of protein kinase C (PKC). These cell lines contain a 20- to 53-fold increase in PKC activity and exhibit dramatically enhanced morphologic changes following exposure to the tumor promoter 12-O tetradecanoyl phorbol-13-acetate (TPA). They grow to a high saturation density in monolayer cultures and, when maintained at postconfluence, develop small, dense foci. In contrast to control cells, which display complete anchorage dependence, PKC-overproducing cells form small colonies in soft agar in the absence of TPA and large colonies in the presence of TPA. Thus, the mere overproduction of a single form of PKC is sufficient to confer multiple growth abnormalities in rat fibroblasts. These results provide direct evidence that PKC plays a critical role in growth control and that it mediates several of the cellular effects of the phorbol ester tumor promoters. They also suggest that the activation of PKC may be of central importance in the process of multistage carcinogenesis. PMID- 3345565 TI - Molecular cloning of the cDNA for human tissue factor. PMID- 3345564 TI - Enhancer-origin interaction in plasmid R6K involves a DNA loop mediated by initiator protein. AB - Initiation of DNA replication from ori beta of plasmid R6K requires the presence of the ori gamma sequence in cis. We demonstrate that binding of initiator protein to the seven strong, tandem binding sites in gamma increases binding of the protein at the very weak binding site present in ori beta by cooperativity at a distance. The gamma-beta interaction via the initiator results in a DNA loop, as revealed by the novel technique of cyclization enhancement and as confirmed by exonuclease III protection, electron microscopy, and chemical footprinting. The protein-mediated gamma-beta interaction in vitro suggests that the cooperative interaction of gamma-bound protein with the beta sequence by DNA looping is an early step in the initiation of DNA replication at the beta origin of R6K. PMID- 3345566 TI - Contaminant found in antiserum. PMID- 3345568 TI - Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain. AB - Prolactin gene expression is negatively regulated by glucocorticoids, and by estrogens when positive estrogen regulatory elements in the prolactin gene are removed. Mutational analysis of estrogen receptor confirms that inhibition is a function of receptor, and that transcriptional activation and inhibition require distinct, separable structural elements. Inhibition is dependent on a 63 amino acid region (amino acids 251-314) distinct from the DNA-binding and steroid binding domains. The comparable region of glucocorticoid receptor confers inhibitory actions on a hybrid receptor. Multiple, nonoverlapping sequences in the rat prolactin 5'-flanking genomic region that confer inhibition by both steroid hormones contain related cis-active elements that bind a common, tissue specific positive transcription factor, called Pit-1. Experimental results indicate that positive and negative transcriptional effects of estrogen receptor are mediated by separate functional domains, and suggest the protein-protein interactions between steroid hormone receptors and other transcription factor(s) mediate inhibition. PMID- 3345567 TI - Nuclear import can be separated into distinct steps in vitro: nuclear pore binding and translocation. AB - Large nuclear proteins must possess a signal sequence to pass through the nuclear pores. Using an in vitro system, we have been able experimentally to dissect nuclear protein transport into two distinct steps: binding and translocation. In the absence of ATP, we observe a binding of nuclear proteins to the pore that is signal sequence-dependent. Translocation through the pore, on the other hand, strictly requires ATP. These steps, visualized in the fluorescence and electron microscopes, were observed both with a natural nuclear protein, nucleoplasmin, and a synthetic nuclear protein, composed of the signal sequence of SV40 T antigen coupled to HSA. When a mutant signal sequence was coupled to HSA, neither transport nor binding were observed, indicating that both result from the presence of a functional signal sequence. An inhibitor of transport, the lectin WGA, also arrested nuclear proteins in a bound state at the cytoplasmic face of the pore. Therefore, only the translocation step is sensitive to the inhibitor WGA, which is known to bind specifically to proteins of the nuclear pore. PMID- 3345569 TI - Expression of Mo3e antigen by cultured human umbilical vein endothelial cells (HUVEC) stimulated by phorbol myristate acetate (PMA) and related pharmacological inducers of protein kinase C. AB - Mo3e is a protease-sensitive membrane antigen (p75,50) selectively expressed by human monocytic cells (monocytes and U-937 cells) stimulated in vitro by exposure to a variety of activating factors, including phorbol diester compounds, bacterial lipopolysaccharide (LPS), and muramyl dipeptide (MDP)(R.F. Todd et al., J. Immunol. 135, 3869, 1985). Here we report that primary and multiply-passaged cultures of HUVEC also express the Mo3e determinant after stimulation by phorbol myristate acetate (PMA) and related inducers of protein kinase C. As measured in a radioimmunoassay of anti-Mo3e antibody binding to monolayer cultures of HUVEC, unstimulated cells bore little if any Mo3e. After culture for 4-120 hr in medium containing PMA, 4 beta-phorbol dibutyrate, 4 beta-phorbol didecanoate, or mezerein (each at a concentration of 81 nM), or 1-oleoyl-2-acetoyl-sn-3-glycerol (1 mM), HUVEC were found to selectively express the Mo3e determinant. The magnitude of expression was dependent upon the concentration of the stimulus, maximal by 24 hr, and inhibited by cycloheximide. The combination of PMA and the calcium ionophore, ionomycin, had an additive or synergistic effect on HUVEC Mo3e expression. The biologically inactive phorbol compounds 4 beta-phorbol and 4 alpha-phorbol didecanoate failed to stimulate Mo3e expression. Also inactive as inducers of HUVEC Mo3e expression were crude lymphokine and monokine supernatants, recombinant human lymphokines (interferon-gamma and interleukin-2), recombinant human monokines (interleukin-1 and tumor necrosis factor), bacterial cell wall products including LPS and MDP, pharmacologic agents that increase intracellular cyclic adenosine monophosphate (prostaglandin E2, cholera toxin, theophylline, isoproterenol and isobutylmethylxanthine), lectins (Con A and PHA), and heparin. These results indicate that Mo3e is an inducible plasma membrane antigen of not only mononuclear phagocytes but also cultured HUVEC. PMID- 3345570 TI - Glutathione and metallothioneins as cellular defense against cadmium toxicity in cultured Chinese hamster cells. AB - To evaluate the protective role of cell glutathione (GSH) against the toxicity of cadmium, the effect of GSH depletion on the metal toxicity was investigated and the role of glutathione was compared with that of zinc-induced metallothioneins (MTs). A 6-h incubation of cultured Chinese hamster V79 cells with 0.2 mM L buthionine-SR-sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase, resulted in approx. 95% depletion of GSH in the cells. The depletion of GSH did not influence the rate of cell growth, the amount of cell protein or the chromosome structure during culture for at least 24 h. Cells depleted or not depleted of GSH were challenged with (1-5).10(-5) M CdCl2 for 2 h and subsequent cell growth was evaluated. The cytotoxicity of cadmium was enhanced with increasing duration of BSO pretreatment and was correlated with the decrease of cell GSH, indicating that GSH constitutes a cellular defense against toxicity by cadmium. Inducibility of MTs by zinc was investigated in cultured V79 cells. Incubation of the cells with 1.10(-4) M zinc acetate did not result in accumulation of MTs over the control values for up to 2 h. Thereafter, however, the synthesis of MTs increased with increasing duration of zinc treatment and an approx. 9-fold increase in the amount of MTs was observed 10 h after addition of zinc. Depletion of cell GSH by BSO did not much influence the increased accumulation of MTs by zinc. In contrast, zinc at the same concentration did not influence the level of cell glutathione up to 12 h. The cytotoxicity of cadmium was markedly reduced in the cells pretreated with zinc and the protective effect of zinc was dependent upon duration of pretreatment, being parallel with the increased accumulation of MTs. Protection of cells from cadmium toxicity by zinc pretreatment was as or a little more effective in the cells depleted of GSH as in those not depleted. Thus, glutathione appears to be an intrinsic protector against cadmium toxicity, while MTs serve as an induced cellular defense that is mobilized against heavy metal stress, but takes more than 2 h to accumulate in significant amounts. Accordingly, it is suggested that GSH and MTs have cooperative protective roles against cadmium toxicity, as an initial defense for the former and a second-stage defense for the latter. PMID- 3345571 TI - Acetaminophen protects human erythrocytes against oxidative stress. AB - Acetaminophen protects human erythrocytes against various modes of oxidative stress. Protection against ozone-induced damage can be explained by a direct scavenging reaction between the drug and ozone. With t-butylhydroperoxide acetaminophen appeared to be an effective scavenger of radicals, generated in secondary reactions. The protection by acetaminophen against t-butylhydroperoxide and hydrogen peroxide-induced lipid peroxidation and K+-leakage can be explained along these lines. In all cases the protective effect of acetaminophen was attended with covalent binding of acetaminophen to membrane proteins. PMID- 3345572 TI - Metabolic activation and toxicity of a DDT-metabolite, 3-methylsulphonyl-DDE, in the adrenal zona fasciculata in mice. AB - Whole-body autoradiography of 14C-labelled 3-methylsulphonyl-DDE (3-MeSO2-DDE) in female C57BL mice revealed a heavy accumulation in the adrenal cortex. Fairly high radioactivity appeared in the nasal mucosa and fat, while the labelling of the liver was intermediate. The adrenal radioactivity remained largely unextracted in tissue-sections treated with organic solvents. In the liver and intestinal contents the radioactivity was partly extracted, whereas in all other tissues almost completely extracted. According to light microscopic autoradiography, the tissue-bound adrenal radioactivity was confined to the zona fasciculata, leaving the other adrenal zones devoid of bound material. Incubation of 3-MeSO2-DDE with adrenal tissue (300 X g supernatant) revealed a dose- and time-dependent covalent binding to protein and formation of water-soluble metabolites. The cytochrome P-450 inhibitors metyrapone and carbon monoxide inhibited both covalent binding and polar metabolite formation. Addition of reduced glutathione decreased binding, while polar metabolite formation was increased. Histopathological examination of adrenals from 3-MeSO2-DDE-treated mice revealed extensive vacuolation and necrosis of the zona fasciculata 1-12 days after single doses down to 25 mg/kg. Degenerative changes were observed at 12.5 mg/kg. In contrast to 3-MeSO2-DDE, 14C-labelled 3,3'-bis(methylsulphonyl) DDE was not accumulated in the adrenal cortex. 3-MeSO2-DDE is thus a persistent environmental pollutant with a unique ability to produce acute toxicity subsequent to metabolic activation in a mammalian tissue. PMID- 3345573 TI - Enhanced potentiation of cisplatin cytotoxicity in human ovarian carcinoma cells by prolonged glutathione depletion. AB - We have determined the effect of extended glutathione (GSH) depletion on cis diamminedichloroplatinum(II) (DDP) cytotoxicity in parent and DDP-resistant human ovarian carcinoma cells. Cells were exposed to 50 microM buthionine sulfoximine (BSO) for 48 h and exposed to DDP for the last 24 h of this time. This treatment protocol sensitized 2008 cells to DDP. The dose modification factor (DMF) defined as IC50 control cells/IC50 GSH depleted cells was 1.6 +/- 0.5 (N = 9). DDP resistant cells selected by acute, high dose DDP exposure were also sensitized by this treatment; the DMF in the 3-6-fold resistant 2008/DDP cells was 2.4 +/- 1.2 (N = 9). The sensitization was not significantly greater in the resistant cells than in the parent cells (P greater than 0.05). When the rebound of GSH following BSO exposure was reexamined, the GSH levels were found to rise rapidly following trypsinizing and plating. BSO treatment following DDP exposure had no effect on DDP cytotoxicity in 2008 and 2008/DDP cells. These results indicate that simply depleting GSH prior to DDP exposure is not sufficient for sensitizing these cells to DDP. In contrast to the potentiation of nitrogen mustard cytotoxicity, exposure to GSH depletion must be maintained during DDP treatment for enhancement of DDP cytotoxicity to occur. PMID- 3345575 TI - In vitro study of the aromatic hydroxylation of 1-methyltetrahydro-beta-carboline (methtryptoline) in rat. AB - The incubation of 1-methyltetrahydro-beta-carboline (1-MeTHBC) with hepatocytes isolated from 3-methylcholanthrene-treated rats led to formation of the 5-, 6- and 7-hydroxylated products. The hydroxylating activity was associated with the microsomal fraction as indicated by testing different subcellular fractions. The highest activity for hydroxylating 1-MeTHBC was found in liver which was about ten times as active as lung. Only a trace amount of hydroxylating activity was present in brain and kidney tissue. Analysis using chiral gas chromatography revealed an unequal abundance of enantiomers in all three products. The formation of the 5-, 6- and 7-hydroxylated products was confirmed in vivo by analysis of 24 h urine samples after intraperitoneal administration of 1-MeTHBC to 3 methylcholanthrene-treated rats. PMID- 3345574 TI - Hemoglobin-catalyzed transformation of elliptinium acetate into electrophilic species. Evidences for oxidative activation of the drug in human red blood cells. AB - The anti-tumor drug N2-methyl-9-hydroxyellipticinium acetate (NMHE, Celiptium) after incubation with various N or S containing amino acids (alanine, histidine, aspartic acid, cysteine, glutathione) with hemoglobin and hydrogen peroxide or an organic peroxide (terbutylhydroperoxide) leads to the formation of the corresponding covalent binding adducts, via an oxidative activation. The formation of the covalent adduct glutathione-elliptinium was also demonstrated in human red blood cells. The importance of such process under in vivo conditions is discussed. PMID- 3345576 TI - c-H-ras and c-K-ras gene hypomethylation in the livers and hepatomas of rats fed methyl-deficient, amino acid-defined diets. AB - The extent of methylation of the c-H-ras and c-K-ras oncogenes was compared in neoplastic and preneoplastic livers of rats fed one of several methyl-deficient, amino acid-defined diets for 18 months, with or without a preceding initiating dose of diethylnitrosamine (DEN). The restriction endonucleases MspI, HpaII, HhaI, PaeR71 and XhoI were used for studying the extent and pattern of DNA methylation. The results indicated that both c-H-ras and c-K-ras oncogenes were hypomethylated in all DNA samples derived from both neoplastic and preneoplastic livers of rats fed any of the methyl-deficient diets used, regardless of whether or not the rats had received an initiating dose of DEN. It thus appears that dietary methyl deficiency does indeed lead to hypomethylation of ras genes in the DNAs of the resulting tumors. However, the significance of this hypomethylation in the tumorigenic process is not clearly understood. PMID- 3345577 TI - DNA binding by 1-nitropyrene and 1,6-dinitropyrene in vitro and in vivo: effects of nitroreductase induction. AB - 1-Nitropyrene, the predominant nitropolycyclic aromatic hydrocarbon found in diesel exhaust, is a mutagen and tumorigen. 1,6-Dinitropyrene is present in diesel exhaust in much smaller quantities than 1-nitropyrene, but is much more mutagenic and carcinogenic. In an attempt to understand this difference in biological potencies, we have compared the extent of DNA binding by these two nitropyrenes in vivo. We have also determined the effect of 1-nitropyrene pretreatment upon the induction of nitroreductases and the subsequent DNA binding by both 1-nitropyrene and 1,6-dinitropyrene. Covalent DNA binding by 1 nitropyrene could not be detected in vivo; however, 1,6-dinitropyrene formed N (deoxyguanosin-8-yl)-1-amino-6-nitropyrene as the major DNA adduct in rat liver, kidney, urinary bladder and mammary gland, with the highest levels being found in the bladder. The capability of liver microsomes to catalyze the oxidative metabolism of 1-nitropyrene was unchanged after treating rats with 8 mg/kg 1 nitropyrene. Cytochrome P-450, NADPH-cytochrome P-450 reductase and cytochrome b5 levels were also unchanged, while slight increases were detected in NADH cytochrome b5 reductase and epoxide hydrase activities. Liver cytosolic and microsomal nitroreductase activities toward both 1-nitropyrene and 1,6 dinitropyrene were increased 2-fold, and cytosolic nitrosoreductase activity toward 1-nitrosopyrene and 1-nitro-6-nitrosopyrene was elevated by approximately 20%. DNA binding of both 1-nitropyrene and 1,6-dinitropyrene in vitro was 2-fold higher when using cytosol from 1-nitropyrene-pretreated rats. However, pretreatment of rats with 1-nitropyrene only slightly increased the amount of in vivo DNA binding by 1,6-dinitropyrene except in kidney where there was a 60% increase. These results indicate that although nitroreduction is involved in DNA adduct formation by 1,6-dinitropyrene, additional factors (e.g. O-acetylation) limit the extent of DNA binding in vivo. PMID- 3345578 TI - Use of ascorbic acid to inhibit nitrosation: kinetic and mass transfer considerations for an in vitro system. AB - Ascorbic acid and ascorbate ion (denoted together as ASC) inhibit nitrosation by competing for the nitrosating agents formed from nitrite (e.g. N2O3, NO+ and NOSCN). ASC is oxidized irreversibly by this reaction and the nitrite equivalents are reduced to nitric oxide (NO). In open, aerobic systems the effective stoichiometry of the reaction between ASC and nitrite is not fixed, but is determined by a competition between the physical removal of NO (and NO2) from the system and the oxidation of NO by dissolved O2. The oxidation of NO reconverts it to a nitrosating agent which may react again with the remaining ASC. To determine the conditions under which ASC is most effective as a nitrosation inhibitor, we examined the kinetics of the reactions between nitrite and ASC and between nitrite and proline. These reactions were studied in open shaker flasks as functions of pH, anion composition (SCN- and Cl-), temperature, and gas-liquid mass transfer rate. At lower mass transfer rates, at lower pH and/or in the presence of SCN- or Cl-, relatively more ASC was consumed by a given amount of nitrite. Increased temperature caused more or less ASC to be consumed by a given amount of nitrite, depending on the conditions. A mathematical model of the reactions and mass transfer steps was developed which describes each of these features. The model predicts the variable stoichiometry of the reaction between nitrite and ASC in open, aerobic systems, and clarifies the mechanisms by which ASC inhibits nitrosation. PMID- 3345579 TI - Effects of ascorbic acid and thiocyanate on nitrosation of proline in the dog stomach. AB - To elucidate the factors governing the formation of N-nitrosamines in the stomach, the formation of N-nitrosoproline (NPro) was studied under controlled conditions, using a dog equipped with a Thomas cannula. Solutions containing nitrite, proline and in some cases ascorbic acid and/or SCN-, were infused into the stomach and samples taken to determine gastric [nitrite], [NPro], [ASC], [SCN ] and pH as functions of time. (Brackets indicate molar concentrations; ascorbic acid and ascorbate ion are denoted together by ASC.) Previous work showed that the rapid decline of [nitrite] in the stomach was due primarily to absorption. Additional experiments here in which ASC, proline or NPro were infused together with a non-absorbable marker, in the absence of nitrite, demonstrated that there was negligible absorption or secretion of these substances in the stomach. Thus, changes in [ASC] and [NPro] with time could be interpreted quantitatively in terms of rates of chemical reaction and dilution of the stomach contents. A mathematical model, based on mass balance equations for the various chemical species and chemical kinetic data obtained previously from in vitro studies, was developed for this purpose. The ability of ASC to inhibit nitrosation (by reaction with nitrite) was shown to be highly dependent on initial [ASC] and on the rate of entry of O2 into the stomach from blood. The rate of NPro formation in the absence of ASC and SCN-, the inhibitory effects on nitrosation of ASC and the catalytic effects of SCN-, were all accurately predicted by the mathematical model. This suggests that similar models may prove useful in estimating rates of intragastric N-nitrosation reactions in humans, under various assumed conditions. PMID- 3345580 TI - Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S-transferase placental form positive foci in rats--an approach for a new medium-term bioassay system. AB - A large series of assays of the hepatocarcinogenic potential of 112 different compounds were carried out using a rapid bioassay system developed in this laboratory based on the two-step concept of hepatocarcinogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p. and starting 2 weeks later were treated with test compounds for 6 weeks and then killed, all rats being subjected to two-thirds partial hepatectomy (PH) at week 3. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive (GST-P+) foci in the liver with those of the corresponding control group given DEN alone. Positive was scored for a significant increase in the value of GST-P+ foci, negative for no change or a decrease. Results were compared to reported Salmonella/microsome and long-term carcinogenicity test findings. Of the liver carcinogens, 10 out of 11 (90.9%) mutagenic, and 11 out of 13 (84.6%) non-mutagenic compounds gave positive results (mean, 87.5%). Carcinogens other than the hepatocarcinogens gave less positive results (two out of 17, 11.8%). None of the compounds reported as non carcinogenic demonstrated positivity suggesting that the assay system does not suffer from the disadvantage of false-positive results. The protocol system also provided information concerning the inhibitory potential of compounds such as anti-oxidants. It is concluded that the present experimental protocol which requires far fewer animals and shorter duration than a long-term carcinogenicity test has practical applications for the rapid and economical screening of environmental hepatocarcinogens and their inhibitory agents. PMID- 3345581 TI - Effects of hyperoxia on growth of experimental lung metastasis. AB - Mice were given i.v. injections of various tumor cell lines and, beginning 24 h later exposed for 3 weeks to 70% oxygen. Hyperoxia reduced the number of lung colonies derived from MT-7 cells (originally a mammary carcinoma) and of the lung tumor derived cell lines 498 and Line-1 early passage. Lung colonies derived from Line-1 late passage, lines M109, B16-F10 and Lewis lung carcinoma were oxygen resistant. Lung metastases following i.m. injection of MT-7 cells were oxygen sensitive and metastases derived from B16-F10 cells or Lewis lung carcinoma were oxygen resistant. Pre-exposure of mice for 48 h to 100% oxygen enhanced colony formation for all cell lines examined whereas exposure to 100% oxygen after i.v. injection only curtailed the growth of the cell lines previously shown to be sensitive to 70% oxygen. There was no correlation between oxygen sensitivity or resistance and the levels of total glutathione or activities of superoxide dismutase (SOD), glutathione reductase or peroxidase or glucose 6-phosphate dehydrogenase in the cell lines. However, upon injection in mice a resistant cell line increased its anti-oxidant defense mechanisms while growing in vivo whereas a sensitive cell line failed to show such adaptation. PMID- 3345582 TI - Expression of carcinoembryonic antigen by adenoma and carcinoma derived epithelial cell lines: possible marker of tumour progression and modulation of expression by sodium butyrate. AB - We have used an indirect immunofluorescence assay to demonstrate the cell membrane expression of carcinoembryonic antigen (CEA) by a pre-malignant colorectal adenoma derived epithelial cell line (PC/AA) and three colorectal carcinoma cell lines (HT29, PC/JW and PC/JW/FI). The results obtained indicated that CEA may be used as a marker for tumour progression up to the point of malignant transformation, after which the selection for anaplastic variants during continuous in vitro culture may result in the subsequent reduction of cell membrane CEA expression. The percentage of PC/AA cells expressing cell membrane CEA increased from 23.1% of diploid early passage (passage 18) cells to 56.0% of aneuploid late passage (passage 58) cells. Although non-tumorigenic, the proportion of PC/AA cells expressing cell membrane CEA at late passage corresponded to that for the PC/JW carcinoma line (56.2%) and is further evidence for the progression of PC/AA in culture. A 3T3 feeder-independent variant of PC/JW (PC/JW/FI) demonstrated a similar percentage of CEA-positive cells as the parental line for the first 21 passages without feeder support, but by passage 27 without 3T3 feeders only 35.3% of cells stained positive. This could be restored to 62.0% by continuous treatment with sodium butyrate (2 mM). A differential growth response to sodium butyrate was noted for the pre-malignant adenoma cell line PC/AA and the carcinoma lines HT29 and PC/JW/FI. Concentrations of sodium butyrate (2 mM) that killed early passage PC/AA cells allowed the late passage PC/AA cells and the carcinoma lines to proliferate, raising the possibility of sodium butyrate acting as a tumour promotor in the human colorectum. PMID- 3345583 TI - Sex- and substrate-dependent changes in hepatic cytosolic glutathione S transferase enzymes produced by dietary choline-deficiency. AB - The effect of 30 week intake of a choline-deficient (CD) diet on cytosolic glutathione S-transferase (GST) activity was investigated in rats of both sexes. GST activities in choline-supplemented (CS) control male cytosol were higher than those in CS-female cytosol for five test substrates--1-chloro-2, 4-dinitrobenzene (CDNB), 1,2-epoxy-3-(p-nitrophenoxy)-propane, trans-4-phenyl-3-buten-2-one, p nitrobenzyl chloride (PNBC) and 1,2-dichloro-4-nitrobenzene (DCNB). The CD dietary regimen produced a relatively uniform decrease in GST activities in male liver to 37-59% of CS-control. With the exception of CDNB conjugation, GST activities in CD-male and CS-female cytosols were not significantly different. On the other hand, in female rats, the CD diet increased GST activity with PNBC and DCNB as substrates to 153 and 204% of respective CS-control female activities; other GSTs were unchanged. Hepatic cytosols from female rats were subfractionated on Whatman CM-52 and subjected to electrophoresis on polyacrylamide gels. The principal finding was that the relative concentration of GST subunit 3 (mol. wt approximately 27 kd) was apparently increased in CD-female rat cytosol; a finding that is consistent with the observed increase in DCNB- and PNBC-conjugation. Thus it is apparent that intake of the tumorigenic CD diet by male rats results in the feminization of GST activity, whereas in females GST subunit 3 is upregulated. The impaired regulation of these enzymes in CD-rats is an early event in relation to the development of hepatocellular carcinoma. PMID- 3345584 TI - An ultimate chemical carcinogen, N-acetoxy-2-acetylaminofluorene, detects non-B DNA structures that are reactive with chloroacetaldehyde in supercoiled plasmid DNA. AB - A model ultimate carcinogen, N-acetoxy-2-acetylaminofluorene (N-acetoxy-AAF), reacts with specific DNA sites in supercoiled plasmid DNA that assume non-B DNA structures. The reaction was studied using supercoiled plasmid DNA harboring either inverted repeats or poly(dG)--poly(dC) sequences, the sequences which are known to adopt non-B DNA structure when under torsional stress. The sites of modification were determined by first digesting the chemically treated DNA with a restriction enzyme, and then by digesting the site of modification with S1 nuclease. Southern blot analysis of resulting DNA fragments revealed that N acetoxy-AAF detects non-B DNA structures in common with another chemical carcinogen, chloroacetaldehyde, which reacts specifically with unpaired adenine and cytosine residues. These results suggest that specific DNA sites with unpaired DNA bases in supercoiled plasmid DNA, and possibly similar structures in chromatin, are hot-spots for certain chemical carcinogen attack. PMID- 3345585 TI - Inhibition of DNA methylase activity by acrolein. AB - Acrolein, a reactive metabolite of cyclophosphamide, may be responsible for bladder cancer induced by cyclophosphamide. DNA methylase was isolated from the liver and urothelium of rats by high salt extraction of purified nuclei. Acrolein at 10 microM inhibited liver and bladder DNA methylase activity by 30-50%. Kinetic studies with the liver enzyme showed a competitive type of inhibition with a Ki of 6.7 microM. Both dithiothreitol and glutathione afforded protection to the enzyme when added to the assay. At near equimolar concentrations of glutathione to acrolein, the methylase retained 80-90% activity. An increase in DNA had no effect on the inhibition by acrolein, whereas increased amounts of protein protected against acrolein inhibition, suggesting that acrolein reacted with the DNA methylase protein. On the other hand, DNA that had been reacted with acrolein was unable to serve as a substrate for DNA methylase. As the DNA adducts increased the methylation of the DNA decreased. Thus, acrolein has the ability to react with DNA and the DNA methylase protein, either of which results in inhibition of DNA methylation. PMID- 3345586 TI - A mammalian cell mutant with enhanced capacity to dissociate a bis-benzimidazole dye-DNA complex. AB - The bis-benzimidazole dyes (specifically Hoechst 33258 and the more lipophilic derivative Hoechst 33342) are non-intercalating AT base pair-specific ligands which bind to cellular DNA by non-covalent association with the minor groove. The interaction of dye with cellular DNA is thought to be the principal pathway for the cytotoxic, mutagenic and DNA-damaging properties of such agents. Upon binding and near UV light excitation, dye molecules exhibit fluorescence enhancement such that dye/DNA association and dissociation in individual cells can be monitored by flow cytometry. We have studied dye uptake and the DNA--dye dissociation characteristics of a Hoechst 33258-resistant mouse cell line (HoeR415) compared to the response of the parental cell line Ltk-. HoeR415 was found to show similar levels of cross resistance (approximately 10-fold) to Hoechst 33258 and Hoechst 33342 compared to parental responses except that the more lipophilic ligand was approximately 30-fold more toxic. Estimates of Hoechst 33342 uptake using flow cytometry or radiolabelling methods indicated that resistance could not be attributed to reduced cellular uptake, low initial levels or different modes of DNA binding. Both cell lines showed similar initial levels of dye-induced DNA strand-breakage. However, Hoechst 33342 resistance did correlate with an enhanced capacity (10-fold) of HoeR415 to remove dye from cellular DNA compared with the relatively long retention (T 1/2 300 min) of ligand by the parental cell line. Our results are consistent with the view that ligand persistence rather than indirect DNA damage is a more important factor in the cytotoxicity of non intercalating DNA-binding ligands. A model is presented of the cellular processes of DNA damage recognition and surveillance for ligands which interact with the minor groove of DNA. PMID- 3345587 TI - Polymorphic N-acetylation capacity in lung cancer. AB - Hepatic N-acetylation phenotype has been suggested to be an important risk factor in the aetiology of bladder cancer. This study explores the N-acetylation capacity of a series of lung cancer cases (126) and two control groups. No overall association of slow or rapid acetylators exists between cancer patients and controls. There is also no difference in the distribution of acetylation phenotypes amongst the histological subtypes. PMID- 3345588 TI - Coefficient induction of pepsinogen 1-decreased pyloric glands and gastric cancers in five different strains of rats treated with N-methyl-N'-nitro-N nitrosoguanidine. AB - Sequential changes of numbers of pepsinogen 1 (Pg 1)-decreased pyloric glands (PDPG) detected by immunohistochemistry and of the incidence of gastric carcinomas were examined in five different strains of rats treated with N-methyl N'-nitro-N-nitrosoguanidine (MNNG;CAS:70-25-7). Male SD (Crj:CD), WKY (WKY/NCrj), Lewis (LEW/Crj), Wistar (Crj:Wistar) and F344 (F344/DuCrj) rats (40 per strain), were given drinking water containing 100 micrograms/ml MNNG for 30 weeks and then normal tap water, and were killed at week 10, 30 and 50 of the experiment. Adenocarcinomas of the glandular stomach were found in nine of 15 SD rats (60%), in eight of 12 WKY rats (67%), in eight of 15 Lewis rats (53%), in three of 13 Wistar rats (23%) and in one of 18 F344 rats (6%) at week 50. These incidences of carcinomas in SD, WKY and Lewis were significantly higher (P less than 0.01) than that in F344 rats. From week 10, the numbers of PDPG in SD, WKY and Lewis rats were significantly greater (P less than 0.01) than that in F344 rats. From week 30, the numbers of PDPG in Wistar rats were also significantly greater (P less than 0.05-0.01) than that of F344. The susceptibility of rats to induction of gastric carcinoma by MNNG correlated with the susceptibility to induction of PDPG by MNNG in each strain, suggesting that induction of PDPG is a preneoplastic change in chemical gastric carcinogenesis. PMID- 3345589 TI - Intestinal first-pass metabolism of nitrosamines. 2. Metabolism of N nitrosodibutylamine in isolated perfused rat small intestinal segments. AB - In a previous study a high first-pass metabolism of N-nitro-sodi-[1 14C]butylamine (NDBA, 0.32-730 microM) has been shown in isolated perfused rat small intestinal segments. In the present work the identification and quantitation of metabolites in samples of perfusate and absorbed fluid (absorbate) is reported. After HPLC enrichment and purification five metabolites could be identified by GLC-MS: N-nitrosobutyl-(3-hydroxybutyl)amine (NB3HBA), N nitrosobutyl-(4-hydroxybutyl)amine (NB4HBA), N-nitrosobutyl-(3 carboxypropyl)amine (NB3CPA), N-nitrosobutyl-(2-hydroxy-3-carboxypropyl)amine (NB2H3CPA) and N-nitrosobutylcarboxymethylamine (NBCMA), representing greater than 95% of total metabolites. omega-hydroxylation leading to NB4HBA and NB3CPA accounted for 75-95% of total metabolites. The formation of their follow-up products NB2H3CPA and NBCMA was too small for quantitative analysis. In absorbate NB3CPA was by far the most important metabolite. The hydroxylation of NB4HBA to NB3CPA was more efficient in jejunal as compared to ileal segments. omega-1 hydroxylation to NB3HBA and, as reported previously, alpha-hydroxylation were only minor metabolic pathways. In conclusion, a high first-pass metabolism of NDBA to the proximate bladder carcinogen NB3CPA takes place during its absorption in rat small intestine. This is in contrast to the observation in rat liver preparations, where alpha- and omega-1-hydroxylation are the predominant pathways. The intestinal first-pass metabolism may play a key role explaining the increased incidence of bladder tumors in rats after low oral doses of NDBA. PMID- 3345590 TI - Intestinal first-pass metabolism of nitrosamines. 3. Identification of metabolites of N-nitrosodiamylamine. AB - In a previous study a high first-pass metabolism of N-nitrosodi-[1-14C]amylamine (NDAA, 0.59-350 microM) has been shown in isolated perfused rat small intestinal segments. In the present work the identification of metabolites in samples of perfusate and absorbed fluid (absorbate) is reported. After HPLC enrichment and purification five metabolites could be identified by GLC-MS which are the result of omega- and omega-1-hydroxylation, N-nitrosoamyl-(5-hydroxyamyl)amine (NA5HAA), N-nitrosoamyl-(4-hydroxyamyl)amine (NA4HAA), N-nitrosoamyl-(4-oxoamyl)amine (NA4OAA), N-nitrosoamyl-(4-carboxybutyl)amine (NA4CBA), and N-nitroso-amyl-(2 carboxyethyl)amine (NA2CEA). In rat urine the presence of only two of these metabolites, NA4HAA and NA2CEA, has been reported in the literature. PMID- 3345591 TI - The tumor-promoter-induced release of phosphorylated fibronectin from human lung fibroblasts. AB - The role of fibronectin (FN) phosphorylation was examined for its involvement in tumor-promoter-induced FN release from normal fibroblasts. We investigated phosphorylated FN in spent media and in cell layers of human lung fibroblasts (HLF) cultured in the presence and absence of the tumor-promoter 12-O tetradecanoylphorbol-13-acetate (TPA). Our data, obtained by metabolic labeling of HLF with [32P]orthophosphate, revealed that 32P-labeled FN accumulated rapidly in the cell layer in the absence of TPA. With TPA present, accumulation of 32P labeled FN at the cell layer of HLF was much slower than under control conditions. On the other hand, treatment of the cells with TPA caused a marked increase in the amount of medium-released FN. This increase in released FN, however, was caused by unlabeled FN and was not paralleled by an increase in 32P labeled FN. We investigated the ability of FN from normal and TPA-treated cells to bind to normal HLF monolayers. We found no difference in re-binding ability, regardless of whether FN was derived from cell extracts of control cultures (showing highly phosphorylated FN) or from the medium of TPA-treated cultures with low phosphorylation of FN. PMID- 3345592 TI - Hemodynamic and metabolic effects of ethanol in canine hemorrhagic shock. AB - Ethanol has been reported to cause myocardial suppression, exaggerated hypotension, and increased mortality in various animal models of hemorrhagic shock. Previous studies have not used a fixed-volume graded hemorrhage model and have not monitored cardiac output or metabolic parameters such as serum glucose and lactate levels. We studied hemodynamic and metabolic changes after administration of ethanol in a 50% graded hemorrhage model in conditioned, anesthetized beagles after orogastric ethanol loading. The hemorrhage was done over a 60-min period followed by a 90-min stabilization period. The ethanol group (n = 6) had significantly higher heart rates during the stabilization period. Mean arterial pressures (MAP) were lower in the ethanol group during the stabilization period. The change from baseline MAP 30 min after hemorrhage was 31% in the control group and -53% in the ethanol group (P less than .05 using Wilcoxon ranked sum test). Serum glucose and lactate levels were higher in the ethanol group. These results indicate that ethanol impairs hemodynamics and alters glucose and lactate metabolism in dogs in the fixed-volume graded hemorrhage model. The effect of these changes on morbidity and mortality remains to be determined. PMID- 3345593 TI - Metabolic effects of partial reversal of pyruvate dehydrogenase activity by dichloroacetate in sepsis. AB - The metabolic effects of dichloroacetate on carbohydrate metabolism were investigated in normal fed, sterile inflammatory, and chronic septic animals. Chronic sepsis, but not sterile inflammation, was associated with elevated plasma, liver, and skeletal muscle lactate concentrations. Sodium dichloroacetate significantly reduced both plasma and intracellular pyruvate and lactate concentrations in all conditions examined, while plasma glucose concentrations remained unchanged. Decreased tissue metabolite concentrations were associated with a significantly increased active pyruvate dehydrogenase complex in liver and skeletal muscle in each of the conditions examined. In liver, dichloroacetate fully activated (greater than 85%) the pyruvate dehydrogenase complex under all conditions. In skeletal muscle from chronic septic animals, the dichloroacetate induced increases in active pyruvate dehydrogenase were significantly less than those observed in non-septic animals. The data suggest that although dichloroacetate can partially reverse the sepsis-induced effects on skeletal muscle pyruvate dehydrogenase activity, there may be additional regulatory factors in skeletal muscle from septic animals. The dichloroacetate stimulation of the pyruvate dehydrogenase activity may provide a pharmacological method for reducing the elevated lactate concentrations observed in chronic severe sepsis. PMID- 3345594 TI - Splanchnic artery occlusion shock in the rat: effects of the calcium entry blockers nimodipine and verapamil. AB - Splanchnic artery occlusion (SAO) shock made by clamping splanchnic arteries for 45 min was performed in female rats infused for 30 min with vehicle, nimodipine, and verapamil before, during, or after SAO. Survival time, macrophage phagocytosis and killing, and white cell count were evaluated in conscious rats. Shocked animals pretreated with vehicle exhibited 24.6 +/- 0.9% phagocytic activity, 5.1 +/- 0.7% killing activity, and survived 177 +/- 1.7 min. Leukopenia was also present. Sham animals survived more than 300 min, and showed the following values: phagocytosis = 52.8 +/- 0.6%, killing = 18.8 +/- 0.6%. Pretreatment with nimodipine (1 microgram/kg/min x 30 min, intravenously [IV]) before SAO significantly prolonged survival time (274 +/- 4.7 min) and improved phagocytosis (38.1 +/- 0.6%) and killing (16.1 +/- 1.1%), but did not change leukopenia. Lower doses of nimodipine (0.25 and 0.5 microgram/kg/min x 30 min, IV), and all the doses of verapamil (100 and 200 micrograms/kg/min x 30 min, IV), when infused before SAO, were ineffective. Neither nimodipine nor verapamil, when infused for 30 min either during or immediately after SAO, were able to influence survival, macrophage functions, or white cell count. Moreover, nimodipine (5, 10, and 25 microM), when added "in vitro" to macrophages collected from SAO-shocked rats, significantly enhanced their phagocytic activity, while verapamil (100 and 200 microM) did not change it. Finally, in anaesthetized rats nimodipine pretreatment had a beneficial effect on the cardiovascular changes occurring during SAO shock. These data suggest that nimodipine has a beneficial effect in SAO-shocked rats only when given before SAO. PMID- 3345595 TI - Are instrument evaluations worthwhile? PMID- 3345596 TI - Definitive characterization of uric acid as an interferent in peroxidase indicator reactions and a proposed mechanism of action. AB - We have characterized and identified uric acid as an interferent to peroxidase catalyzed reactions where hydrogen peroxide is generated at relatively low concentrations. The implications of these findings are important for those utilizing peroxidase as an indicator reaction where low primary substrate concentrations require their preliminary extraction or chemical modification. We have shown that the elimination of uric acid as an interferent from biologic fluid obviates the necessity for such treatment. In amniotic fluid, our data suggests that uric acid represents the only interference to peroxidase-catalyzed reactions, especially when using p-substituted phenols as proton donors. The removal of uric acid has been shown to eliminate hydrogen peroxide reduction and should allow for an increase in sensitivity and specificity for measurements incorporating a peroxidase-coupled indicator reaction, hence, more effective use of these reaction sequences. To our knowledge, this is the first report of a mechanism to eliminate hydrogen peroxide reduction in amniotic fluid. PMID- 3345597 TI - A new enzymatic approach for estimating total and direct bilirubin. AB - We designed an enzymatic assay for total (TBil) and direct bilirubin (DBil), the principle of which involves measuring the decrease in absorbance at 450 nm produced by bilirubin oxidase from Myrothecium verrucaria. Since TBil and DBil are oxidized at pH 7.2 and 3.7, respectively, the degree of bilirubin oxidation is measurable in each case. An analysis of bilirubin by high-performance liquid chromatography, before and after the enzymatic reaction with bilirubin oxidase, verified the specificity of the enzyme. The results obtained using this method varied linearly with TBil and DBil concentrations up to at least 250 mg/L and 150 mg/L, respectively. Reducing substances, commonly used anticoagulants and hemoglobin showed no apparent interference. The degree of day-to-day precision (CV) for TBil and DBil ranged from 1.2% (206.2 mg/L) to 10.6% (3.5 mg/L) and from 1.8% (84.3 mg/L) to 12.4% (2.1 mg/L), respectively. Values measured using this new method correlated well with those obtained by Malloy-Evelyn's method and the slide method employing the Kodak Ektachem analyzer. PMID- 3345599 TI - Association between the glycation of erythrocyte membrane proteins and membrane fluidity. AB - Erythrocyte membrane ghosts prepared from normal individuals were incubated in vitro at different glucose concentrations for 72 h. Incubation with increasing concentrations of glucose resulted in increased glycation (nonenzymatic glycosylation) of membrane proteins and a decrease of erythrocyte membrane fluidity measured by the use of the fluorescent label pyrene. It would therefore seem likely that the changes in erythrocyte membrane fluidity previously reported in diabetic subjects (1-3) are related to in vivo glycation of membrane proteins as well as to changes in lipid composition, as was previously suggested (2). PMID- 3345598 TI - Reactivity of acetoacetate with alkaline picrate: an interference of the Jaffe reaction. AB - Spectrophotometric, kinetic, and polarographic studies of the interaction of acetoacetate with alkaline picrate have been undertaken in the presence of aqueous NaOH concentrations ranging between 0.50 mol/L and 2.50 mol/L. Spectrophotometric data has substantiated formation of the following acetoacetate picrate complexes: 1:1 red, 490 nm; 2:1 orange, 390 nm; and 3:1 colorless, 265 nm. Depending upon the time of measurement, the composition of alkaline picrate, and the acetoacetate level in the test samples, acetoacetate may be either a positive or negative interference in kinetic Jaffe methods for the determination of creatinine. Polarograms of alkaline picrate in 0.50 mol/L NaOH showed three well-defined nitro group reduction waves and a more diffuse fourth reduction wave with approximate half-wave potentials of -0.62 V, -0.79 V, -0.94 V, and -1.32 V, respectively. Increasing the concentration of hydroxide and/or acetoacetate resulted in the disappearance of reduction waves 1 to 3 with only reduction wave 4 remaining. Based upon the polarographic results, a trinitro anion structure has been assigned for the 2:1 acetoacetate-picrate complex. PMID- 3345600 TI - Timing of specimen collection is crucial in urine screening of drug dependent mothers and newborns. AB - We compared results of urine drug analysis with clinical data and history to test the usefulness of peripartum drug screening and to establish guidelines for optimal testing. Urine from 28 mothers and 52 babies was analysed. Drugs not suspected by history were found in 10 mothers and six babies. Results assisted in the management of neonatal withdrawal in three babies. Drugs suspected by history were not found in 11/22 mothers and 23/35 babies. About half of these results were associated with delayed urine collection. In 12/28 mothers, drugs administered in hospital could have confused interpretation of screen results. We conclude that urine drug screening without strict protocols for specimen collection is of limited usefulness for management of drug abuse in pregnancy and neonatal drug withdrawal. We favour testing of maternal urine obtained before drugs are administered in hospital. Neonatal urine, if used, should be collected in the first day of life. PMID- 3345602 TI - Innovations in nursing education. PMID- 3345603 TI - The usefulness of exercise-induced QRS axis shift as a predictor of coronary artery disease. AB - The QRS axis of 101 patients with coronary artery disease (CAD) and 57 normal subjects without CAD who underwent coronary arteriograms were measured before and after exercise testing. There was no improvement in the sensitivity of positive axis shifts (15 degrees or greater) for CAD (18%) when compared to the value of positive ST depression (61%). However, the specificity of positive axis shifts for CAD was significantly increased (98%) when compared to the value of positive ST depression (77%). In addition, 39% of those patients with CAD (39 of 101) showed false negative ST depression, but 18% of these patients (7 of 39) showed a positive axis shift. In normal subjects 21% (12 of 57) showed false positive ST depression, but all of the 21% (12 of 12) showed negative axis shift. There was no significant difference in the increments of heart rate between positive ST depression, positive axis shift, and negative ST depression, negative axis shift. No statistical differences in the sensitivity of ST depression and an axis shift for one-, two- and three-vessel diseases were noted. The specificity of left-axis shift for the left anterior descending artery lesion was 98% and the specificity of right-axis shift for the right coronary artery and/or left circumflex artery lesion was 91%. Therefore, the axis shift response is no more sensitive for the detection of CAD than ST depression. However, when a positive axis shift is observed, one can predict two things: the CAD and the localization of the coronary stenosis. PMID- 3345601 TI - Urinary albumin excretion in normal subjects and in diabetic patients measured by a radioimmunoassay: methodological and clinical aspects. AB - We have developed a radioimmunoassay method (RIA) to measure urinary albumin excretion. We determined the albumin excretion rate (AER) (micrograms/min) of 122 healthy subjects and 145 diabetic patients (115 type I, 30 type II). The results indicate that the RIA is sensitive (0.39 +/- 0.08 mg/L), precise (CV 5-8%), and gives reliable results on previously frozen urine samples. The distribution of the AER values in healthy subjects and diabetic patients was not normal. It was normalized by log or square-root transformation of the data. Seventy-three percent of diabetic patients lay within the normal range (0.6-10.6 micrograms/min). Twenty percent could be considered "at risk" to develop overt diabetic nephropathy because their albuminuria exceeded a threshold level of 15 micrograms/min chosen previously as the cutoff value for microalbuminuria. We found no correlation between AER and glycated hemoglobin, and only a weak correlation between AER and diabetes duration in type I diabetic patients. PMID- 3345604 TI - Quantitative grading of exercise stress test for patients with coronary artery disease using multivariate discriminant analysis. AB - A group of 111 male patients who had undergone maximal or symptom-limited maximal exercise stress testing for evaluation of coronary artery disease (CAD) were subjected to coronary angiography. Group I comprised 33 patients with normal or single-vessel disease (SVD), while 78 patients with double-vessel disease (DVD) or triple-vessel disease (TVD) formed Group II. On univariate analysis of the exercise test, the following variables were found to be of significance in discriminating between the two groups: age, exercise duration, double product (heart rate X systolic blood pressure) at peak exercise, duration of ST-segment depression, number of leads showing ST depression, ST depression of 1 mm or more, configuration of the depressed ST segment, and diastolic blood pressure response to exercise. Multivariate analysis however revealed that only the following five variables had significant discriminant power: number of leads showing ST depression, exercise duration, double product, diastolic pressure response, and ST-segment configuration. On the basis of their relative importance, a regression equation was developed to give a quantitative score to individual patients. A score of less than zero detected multivessel disease (MVD) with high specificity (94%) and sensitivity (70%), while a score of 15 or more almost excluded MVD (sensitivity 87%). The scoring system as reported here improved the exercise stress test interpretation when compared with the conventional reporting system. PMID- 3345605 TI - Effect of localized surface cooling of the heart muscle on the high-frequency content of ECG waveforms in dogs. AB - Hypothermia is known to affect the electrophysiology of the myocardium in various ways. A marked increase in action potential duration, combined with a decrease in rate of depolarization and conduction velocity, has been observed. We studied the effect of localized hypothermia of the ventricular myocardium on the high frequency (HF) components of the ECG waveform. Signals were obtained from 6 anesthetized dogs using simultaneous recording of three orthogonal body surface leads before, during, and following surface cooling of different areas of the epicardium. Computer analysis included digital averaging and filtering in a frequency range of 150-250 Hz. For each intervention in each animal, the variance of the average nonfiltered QRS complex was used for a quantitative estimate of the total power, whereas the variance of the derived filtered wave (HF QRS complex) expressed the power content in the HF range. The total power increased during localized cooling of the anterior as well as the inferior epicardial surface, while a clear reduction of power was observed in the HF range. This reduction was shown to be lead dependent and nonuniformly distributed during the course of the QRS. In all cases, hypothermia of either anterior or inferior ventricular epicardium produced a zone of reduced amplitude in the HF QRS complex of at least one lead. Thus, typical changes in the morphology of the HF QRS complex are reliable markers for cooling-induced localized electrophysiological (EP) variations. Therefore, the HF analysis of the body surface ECG may provide noninvasive insight into the EP properties of the myocardium. PMID- 3345607 TI - Endomyocardial fibrosis with massive endocardial calcific deposits. PMID- 3345606 TI - Malignant schwannoma of the heart. AB - Primary cardiac tumor is an extremely rare disease entity. Only three cases of primary malignant cardiac schwannoma, the subject of this report, have been recorded in Japan. Recently, we encountered a case of malignant schwannoma in which retention of pericardial effusion was the first clinical finding. This case was a 30-year-old female, who had dyspnea at work, general fatigue, and fever. Striking cardiac expansion was seen, with a cardiothoracic ratio (CTR) of 69% on chest x-ray. Two-dimensional echocardiograms showed a large volume of pericardial effusion between the side wall of the left ventricle and the epicardium, and the presence of a parenchymatous tumor. An increase in tumor size was detected on chest computer tomography (CT) scan. Using a pump oxygenator, median sternotomy was performed to reach the epicardium. A pale yellow, soft tumor was seen in the left atrium near the left ventricle. Histologically, the patient was diagnosed as having a malignant schwannoma. We have reported a case of primary malignant schwannoma which was surmised to have arisen from the boundary between the atrium and the ventricle. PMID- 3345608 TI - QT intervals as an index of high serum calcium in hypercalcemia. AB - The relationship between QT interval and serum calcium concentration (s-Ca) was examined in 9 hypercalcemic (s-Ca greater than 11 mg/dl) patients. Three QT intervals corrected by Bazett's formula were used for the analysis: the intervals from the beginning of the QRS to the onset (QoTc), the apex (QaTc), and the end of T wave (QeTc). The measurements of s-Ca and other electrolytes were made on the blood sample taken on the same day of the electrocardiogram (ECG) recordings. The normal range of s-Ca and three QTc intervals was determined in 50 outpatients with no cardiac disease. Three QT intervals in the hypercalcemic patients were significantly shortened with a diminution in the s-Ca. The QTc intervals showed significant negative correlation with s-Ca. Sensitivity of QoTc, QaTc, and QeTc in predicting high s-Ca was 83%, 57%, and 39%, respectively, and specificity was 100%, 100%, and 89%. The PQ interval tended to be prolonged in the case of hypercalcemia, but the change was statistically insignificant. These observations suggest that QT intervals can serve as an indicator of high s-Ca and that the QoTc seems to be a good indicator of the three QTc's. PMID- 3345609 TI - Iatrogenic cardiac tamponade after central venous catheter. AB - Myocardial perforations with a central venous catheter are rare in adults (67 cases published since 1968). These accidents are fatal in more than two-thirds of the cases owing to confusion caused by misleading symptoms which suggest pulmonary embolism. The perforation is generally localized in the right atrium (29 cases), less frequently in the right ventricle (18 cases). The superior vena cava is rarely affected (3 cases). The site of the perforation was not found in the other published cases. Clinical symptoms are signs of tamponade with disorders of cardiac rhythm. An enlargement of the cardiac shadow and an abnormal position of the catheter, buckled or openly intrapericardial, make the diagnosis radiologically. Echocardiography provides some information, but this is often too late for practical application. The diagnosis is made with right catheterization when it shows an equalization of the diastolic pressures. This allows the patient to be watched closely following the pericardial tap, after which a surgical approach may be indicated and performed. Prevention of these iatrogenic accidents must be systematic and strictly controlled for. PMID- 3345610 TI - Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan. AB - Repeated administration of the hepatic lectin blocking agents D-galactose or arabinogalactan completely prevented the settling of metastatic cells of sarcoma L-1 tumor in the liver of Balb/c mice and greatly reduced the colonization process of highly metastatic ESb lymphoma cells of the liver of DBA/2 mice. Therefore, when hepatic lectins were blocked with competitive glycoconjugates, tumor cell colonization of the liver could be prevented in two different model systems. PMID- 3345611 TI - Tumor necrosis can facilitate the appearance of metastases. AB - The non-metastatic murine mammary adenocarcinoma M3 and its metastatic variant MM3 were used to evaluate the role of intratumoral necrosis in cell detachment and metastasis. Accelular extracts from necrotic areas of both tumors increased in vitro cellular detachment from M3 but not from MM3 fragments. Furthermore, the in vivo inoculation of the necrotic extracts within non-metastatic M3 tumors gave rise to pulmonary metastases. Histological studies revealed in M3 a central necrosis limited by an uninterrupted peripheral ring of well preserved cells, while in MM3 necrotic and non-necrotic areas alternated. It is concluded that the distribution of necrosis within the primary tumor by facilitating cell detachment is, at least in part, responsible for the development of metastases. PMID- 3345612 TI - Growth stimulating activity of lung extract on lung-colonizing colon 26 clones and its partial characterization. AB - The effects of lung tissue extract on the cell growth of eight colon 26 tumor clones, four highly and four poorly lung-colonizing clones, were examined in vitro. Addition of lung extract to serum-free medium stimulated the growth of all four of the highly lung-colonizing clones and one of the poorly lung-colonizing clones, but it had minimal effect on the other three poorly lung-colonizing clones. These results indicate that the lung extract contains a growth stimulating activity; it selectively stimulated some of the colon 26 clones including highly lung-colonizing ones. The growth stimulating activity was not dialyzable, was partially destroyed by heating at 56 degrees C or 80 degrees C for 30 min and completely destroyed by trypsin. These results suggest that the activity resides in a protein. Gel filtration chromatography of lung extract on Sephacryl S-200 revealed that the active component was eluted in a molecular weight range of 90,000-120,000. PMID- 3345613 TI - Therapeutic advisory program: an opportunity for clinical pharmacology. PMID- 3345614 TI - Human buccal assay for evaluation of the mucosal irritation potential of drugs. AB - We applied drugs in aqueous gels to the buccal mucosae of normal volunteers to develop an assay of gastrointestinal irritation potential. We studied effects of pH, concentrations, and formulations. We evaluated irritation by subjects' reports of their sensations and observers' grading of visible reactions. On an irritation log ranking scaled 0 to 5, placebo gels produced virtually no irritation, except those formulated at pH 1, 2, and 14. Albuterol, furosemide, and methyldopa produced essentially no irritation. Minutes of exposure to sodium indomethacin, sodium naproxen, and propranolol (at, respectively, pH 8.2, 9.6, and 4.8 and concentrations of 12%, 40%, and 8%) caused ulceration that took up to weeks to heal. Acid forms of naproxen and indomethacin caused minimal or no irritation. Although irritation models based on one gastrointestinal area have limitations, our results indicate that the minimally invasive buccal assay allows ranking of contact irritation potential of drugs and formulations that could aid in selecting optimum formulations for clinical use. PMID- 3345615 TI - Pharmacokinetics of a new angiotensin I converting enzyme inhibitor (delapril) in patients with deteriorated kidney function and in normal control subjects. AB - Pharmacokinetic properties of a new angiotensin-converting enzyme inhibitor, delapril (CV-3317), which converts to two active metabolites (M-1 and M-2) and one inactive metabolite (M-3) after oral administration, were investigated in six subjects with normal, 10 subjects with slight (SRF), and six subjects with markedly (MRF) deteriorated kidney function. The elimination half-life of M-1 was prolonged significantly in subjects with MRF and that of M-3 was also prolonged in subjects with SRF or MRF. The peak plasma drug concentration, time to reach peak concentration (tmax), and AUC were significantly larger in subjects with SRF and MRF than in normal subjects, except for Tmax in subjects with SRF. In M-2 and unchanged delapril, no difference was observed. The 24-hour cumulative urinary excretion of those metabolites was significantly lower in subjects with MRF than in normal subjects. Plasma angiotensin-converting enzyme activity, suppressed at 4 hours in all subjects, remained significantly low in patients with MRF at 24 hours. Blood pressure was reduced more in subjects with chronic renal failure. It was concluded that delapril is excreted mainly through the kidney and its pharmacodynamics and biologic effects are affected by the renal dysfunction. PMID- 3345616 TI - Lorazepam conjugation is unimpaired in burn trauma. AB - A previous clinical study documented impaired hepatic metabolism of diazepam (phase I reaction) after burn injury. In this study, using lorazepam as a marker of hepatic glucuronidation, we tested the hypothesis that after burn injury, phase II reactions may be less impaired than phase I reactions. Ten burned patients and 10 age-, weight-, and sex-matched control subjects were studied after a 2 mg bolus dose of lorazepam. Burned patients had received multiple medications, whereas control patients were not taking any medication. The burned patients were studied at a mean (+/- SE) of 22 (+/- 4.6) days after burn injury. The burned patients had increases in total volume of distribution (2.66 +/- 0.55 vs. 1.39 +/- 0.1 L/kg; P less than 0.02) and clearance (4.28 +/- 1.20 vs. 1.16 +/ 0.1 ml/min/kg; P less than 0.01), whereas the half-life was significantly reduced in the burned group (9.6 +/- 1.3 vs. 13.9 +/- 0.9 hours; P less than 0.025). The significantly increased clearance and decreased elimination half-life in burned patients indicates that the elimination kinetics of lorazepam are not impaired and in fact may be enhanced in burned patients. PMID- 3345617 TI - Pharmacogenetics of N-methylation: heritability of human erythrocyte histamine N methyltransferase activity. AB - Histamine N-methyltransferase (HNMT) catalyzes the N tau-methylation of histamine. HNMT is present in many human tissues, including the red blood cell (RBC). Our study evaluated the possible role of inheritance in the regulation of individual variations in human RBC HNMT activity. HNMT activity was measured in RBC lysates from 241 members of 51 nuclear families. After correction for the gender-specific effects of age, the frequency distribution of RBC HNMT activities was unimodal, and activities varied threefold within 2 SDs of the mean. The correlation of HNMT activities in RBCs from 45 pairs of spouses was only 0.070, indicating that shared environment did not result in similar activities among genetically unrelated individuals. Correlation coefficients were also calculated for pairs of genetically related individuals. All of these correlations were significant except the mother-oldest son correlation. The majority of the correlations did not differ significantly from those predicted for a trait with a heritability of 1.0 (100%). Our results demonstrate a significant familial aggregation of human RBC HNMT activity and suggest that inheritance may play an important role in the regulation of variation in the activity of this N methyltransferase enzyme in the human RBC. PMID- 3345618 TI - Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability? AB - The pharmacokinetics of midazolam and its metabolites were studied in 17 patients on mechanical ventilation in a general intensive care unit who were receiving a continuous intravenous infusion of midazolam, adjusted according to the level of induced sedation. Three patients were studied twice. Serum midazolam and alpha hydroxymidazolamglucuronide levels were determined during and after infusion. The sedation level was scored on a four-point scale. Half of the observed patients were still drowsy or asleep 10 hours after termination of midazolam infusion. In only one patient was midazolam serum elimination half-life less than 2 hours and in six patients the half-life was greater than 10 hours. A wide range of midazolam serum levels was associated with adequate sedation, and similarly the midazolam levels at the moment of awakening were highly variable. The serum concentration ratio of midazolam/alpha-hydroxymidazolamglucuronide at the end of the infusion varied from 0.03 to 15.6. Renal function could account for only a part of this variation. PMID- 3345619 TI - Tolerance to alprazolam after intravenous bolus and continuous infusion: psychomotor and EEG effects. AB - A study was undertaken to compare the time course of changes in psychomotor performance and spectral edge (SE) of the EEG and to relate these changes to alprazolam concentrations in a pharmacokinetic/pharmacodynamic tolerance model. Digit symbol substitution (DSS) tests were administered and EEG data were obtained for SE calculation in a four-way crossover study in four normal men. Each treatment consisted of a 2-minute bolus injection followed by an 8-hour infusion. Treatment A, placebo, consisted of a 50% propylene glycol injection followed by a saline infusion. Active drug treatments were: B, 0.5 mg alprazolam plus saline infusion; C, 2.0 mg alprazolam plus saline; and D, 1.0 mg plus 72 micrograms alprazolam/hr for a total dose of 1.576 mg in 8 hours. For both DSS and SE data, three distinct effect-concentration curves result from the three alprazolam treatments, with successive shifts to the right as dose increases. A tolerance rate constant (kt) of 0.15 hr-1 was calculated from the DSS vs. time data during the 8 hour alprazolam infusion. The Hill equation was altered by using kt in an exponential modification of EC50. The resulting tolerance model describes both DSS and SE vs. concentration data from the rapid-injection and continuous-infusion treatments. PMID- 3345620 TI - The racemic metoprolol H2-antagonist interaction. AB - The effects of concomitant administration of cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of multiple-dose metoprolol were investigated in 12 normal, healthy male volunteers. The pharmacokinetics of metoprolol were assessed in terms of racemic metoprolol and the individual (R)- and (S)-enantiomers with a stereoselective assay. Ranitidine had no effect on the pharmacodynamics or pharmacokinetics of metoprolol. Although not affecting the pharmacodynamics of metoprolol, cimetidine did produce an increase in the bioavailability of metoprolol through inhibition of enzymes responsible for the first-pass elimination of the beta-blocker. The effect was stereoselective, with the major effect being on the less pharmacologically active (R)-enantiomer. PMID- 3345621 TI - Effects of 1-epinephrine on hemodynamics and cardiac function in coronary disease: dose-response studies. AB - To assess the effects of elevated epinephrine levels on cardiovascular performance in patients with coronary artery disease (CAD), epinephrine was infused intravenously into eight patients with normal coronary anatomy and 22 patients with CAD at dose rates of 0.06, 0.12, 0.18, and 0.24 micrograms/kg/min. Hemodynamic responses to epinephrine were not significantly different between the two groups. However, contractility increased significantly more (P less than 0.05) and end-systolic volume decreased significantly more (P less than 0.025) in normal subjects than in those with CAD. Plasma norepinephrine concentrations increased significantly (P less than 0.05) at 0.24 micrograms/kg/min epinephrine, indicating activation of sympathetic nervous system. Epinephrine ischemic thresholds ranged from 652 to 3362 pg/ml. Patients with CAD compared with normal subjects had more frequent ventricular arrhythmias (55% vs. 25%), chest pain (50% vs. 13%), and ischemic ECG changes (73% vs. 13%). These results indicate that although epinephrine induced myocardial ischemia in CAD, hemodynamics and ventricular pump function were maintained. PMID- 3345622 TI - Effect of renal impairment on the pharmacokinetics of cibenzoline. AB - Sixteen subjects completed an open-label study designed to assess the effect of renal impairment on the disposition of cibenzoline. The study included 10 patients with mild or moderate renal impairment creatinine clearance less than 60 ml/min/70 kg) and six healthy subjects in the same age range, each of whom received a single 130 mg oral dose of cibenzoline. The pharmacokinetic parameters observed in the healthy volunteers were similar to those reported previously. Maximum plasma concentration, time of maximum concentration, and apparent volume of distribution after single doses in patients with renal impairment were in the same range as those observed in healthy volunteers. The elimination half-life increased with decreasing renal function from a mean value of approximately 8 hours in healthy volunteers to more than 20 hours in patients with moderate renal impairment. Renal clearance and the fraction of the dose excreted unchanged in the urine decreased with decreasing creatinine clearance. The results of this study suggest that the dosage of cibenzoline should be reduced or the dosage interval increased in patients with reduced renal function to avoid excessive drug accumulation. PMID- 3345623 TI - Pharmacokinetics and hemodynamic effects of nisoldipine and its interaction with cimetidine. AB - Pharmacokinetics, diastolic blood pressure, and heart rate after oral and intravenous nisoldipine were studied in eight healthy subjects without and with cotreatment of cimetidine in a four-way crossover design. After intravenous infusion, elimination half-life (t1/2) was 4.0 +/- 2.3 hours, systemic clearance (CL) was 0.83 +/- 0.17 L/min, and volume of distribution was 1.6 +/- 0.6 L/kg. After oral nisoldipine, t1/2 was 3.8 +/- 1.3 hours and systemic availability was 3.9% +/- 3.5%. During cimetidine, t1/2 and CL were not different. Systemic availability increased to 5.7% +/- 2.8%. After all nisoldipine treatments a significant decrease in supine diastolic blood pressure (mean 10% to 16%) and increase in heart rate (mean 22% to 44%) were observed. Hemodynamic effects until 2 hours after nisoldipine administration could be fitted to a sigmoidal Emax model. At times after 2 hours a second effect peak was observed. Cimetidine inhibits the metabolism of nisoldipine but has no significant influence on hemodynamic parameters. PMID- 3345625 TI - Rhinoplasty. PMID- 3345624 TI - Rhinoplasty: image and reality. AB - The rhinoplasty surgeon must convert a mental image into a surgical reality through aesthetics, anatomy, and analysis. This article attempts to provide a reasoned solution to the recurrent difficulty of progressing from image to reality. PMID- 3345626 TI - Diagnosis and treatment of nasal airway obstruction due to inferior turbinate hypertrophy. AB - Bilateral inferior turbinate hypertrophy is the most common cause of nasal airway obstruction. Treatment by resection is advised. Following this, a significantly improved airway has been demonstrated and no adverse sequelae have been observed or reported. PMID- 3345627 TI - Rhinoplasty and the nasolabial area. AB - The nasolabial area is important to consider in achieving a satisfactory relationship between the nose and the other features of the face; this will result in a natural-looking nose. However, the importance of the entire nose on a particular face should be kept foremost in mind. PMID- 3345628 TI - Rhinoplasty. Ancillary procedures. AB - Assessing facial balance before attempting correction of nasal proportions is critical. Modifications of facial structures, which alter perception of the nose, even with seemingly minor disproportion, can do much to enhance final results. Many of these procedures are conceptually simple, rapidly executed, and overwhelmingly gratifying. PMID- 3345629 TI - Secondary rhinoplasty. AB - During the past 15 years the guest editor has developed new and better procedures for secondary rhinoplasty. These techniques, including ear cartilage grafts, are discussed in this article. PMID- 3345630 TI - Management of the deviated nose. The importance of septal reconstruction. AB - The key to the correction of severely deviated noses is straightening the nasal septum. An emphasis is placed on conservative management of the external nasal framework while being prepared to perform extensive surgery on the deviated septum. If the septum can be modified and repositioned in the midline without losing support to the nose, consistently good functional and aesthetic results are obtained. Several techniques that we have found to be of value in achieving this goal have been discussed and illustrated and three representative cases have been presented. PMID- 3345631 TI - The use of augmentation rhinoplasty techniques for the correction of the non caucasian nose. AB - To refine, enlarge, and enhance the mestizo nose, it is necessary to augment the structural support. The authors report on a series of more than 3000 patients over the last 20 years, exploring the possibilities of autogenous graft for augmentation of the nose. Their series showed minimal resorption of the bone grafts, no loss of volume of the cartilage grafts, and satisfactory long-term results. PMID- 3345632 TI - Trimethylaminuria ('fish-odour syndrome'): a study of an affected family. AB - 1. Beginning with a single propositus, who had been previously diagnosed at the age of 10 as suffering from trimethylaminuria (fish-odour syndrome), both her parents and two sisters were investigated biochemically with respect to their ability to N-oxidize trimethylamine (TMA), both when derived from the diet and when administered exogenously. 2. Both the propositus and a second sister were markedly deficient in their ability to N-oxidize TMA, both when derived from the diet and when given as such; furthermore, both siblings readily developed the symptoms of fish-odour syndrome as characterized by a strong objectionable breath and body odour shortly after the oral administration of TMA (300 mg). 3. At this dose level of TMA, neither of the parents nor the third sister showed any evidence of impaired N-oxidation ability nor did they experience any 'fish-odour' symptoms. 4. With an oral challenge of 600 mg of TMA, both the parents showed a clear impairment of N-oxidation capacity which was not seen in six healthy unrelated volunteers. Both parents experienced a fish-odour syndrome at this level of TMA challenge. 5. The family data support the hypothesis that trimethylaminuria is an inborn error in the ability to N-oxidize TMA which is inherited as an autosomal recessive trait. Furthermore, experience with this family suggests that an oral challenge dose with 600 mg of TMA may be used to identify carriers of the condition. PMID- 3345633 TI - Rate of protein synthesis in skeletal muscle of normal man and patients with muscular dystrophy: a reassessment. AB - 1. Quadriceps muscle protein synthetic rate has been determined in healthy subjects in the post-absorptive (n = 18) and fed (n = 10) states and in patients with a variety of myopathies, by analysis of the enrichment of serial muscle biopsies taken during primed continuous infusion of L-[1-13C]leucine. 2. Quadriceps protein synthetic rates in normal subjects were (mean +/- SD) 0.046 +/ 0.012 and 0.075 +/- 0.014%/h in the post-absorptive and fed states respectively. These results are significantly lower than we previously reported (M. J. Rennie et al., Clinical Science, 1982, 63, 519-523 [1]) but show the same relative differences of direction and magnitude, confirming the effects of feeding previously reported. In patients with muscular dystrophy, muscle protein synthetic rate was, as previously reported [1], much lower in the fed state than in normal subjects. A new finding is that for patients with myotonic dystrophy the rate is also depressed in the post-absorptive state. 3. We suggest that the present estimates in post-absorptive and fed normal subjects be used as reference values for quadriceps mixed muscle protein synthetic rate. PMID- 3345634 TI - Unilateral renal ischaemia in the rat: effect of contralateral nephrectomy and intrarenal flush with phosphate-buffered sucrose. AB - 1. This study examined whether the severity of acute renal failure seen within 4 h of a 45 min period of unilateral occlusion of the renal pedicle could be reduced by removal of the contralateral healthy kidney and/or intrarenal flush with a phosphate-buffered sucrose (PBS50) solution. 2. After ischaemia, unflushed kidneys became oliguric and isosthenuric, with a fall in inulin clearance (Cin) to 0.1% of the pre-ischaemic value. Removal of the healthy contralateral kidney upon release of the occlusion caused no improvement in immediate post-ischaemic function. 3. Intrarenal flush with 1.5 ml of PBS50 resulted in a significantly improved post-ischaemic Cin, with increased urine flow rate and solute excretion; urine was also concentrated. 4. Protection of renal function against ischaemic damage was seen only when kidney tissue remained blood-free and exposed to PBS50 throughout the period of ischaemia, and when the speed of flush was similar to the expected renal blood flow (6 ml/min). Protection did not depend upon the presence or absence of the contralateral kidney. 5. The study also showed that functional removal of one kidney, either by pedicle occlusion or nephrectomy, caused an immediate rise in solution excretion from the contralateral kidney, but Cin remained unchanged. Unflushed severely damaged kidneys showed no compensatory response to unilateral nephrectomy, whereas kidneys flushed with PBS50 exhibited increases in solute excretion similar to those seen in healthy non-ischaemic kidneys. PMID- 3345635 TI - Origins of endogenous noradrenaline overflow during reperfusion of the ischaemic rat heart. AB - 1. Reperfusion of the globally ischaemic isolated rat heart is associated with an enhanced overflow of endogenous noradrenaline (NA) after ischaemic periods of 20, 40 or 60 min but not of 10 min. 2. Reperfusion NA overflow, after 40 min of ischaemia, is suppressed by desipramine and increased when ischaemia follows a period of substrate deprivation. 3. Reperfusion after 40 min of ischaemia is associated with a significant rise in NA concentration despite a simultaneous 20 fold increase in flow. This increase in concentration is abolished by treatment with desipramine or if ischaemia follows a period of substrate deprivation. 4. Reperfusion NA overflow correlates with the reperfusion overflow of an extracellular space marker infused before the ischaemic episode. 5. These results suggest that ischaemia is heterogeneous and that NA is released into regions of particularly profound ischaemia from which it is subsequently eluted during reperfusion. PMID- 3345636 TI - Ventilation and breathlessness on maximal exercise in patients with interstitial lung disease after local anaesthetic aerosol inhalation. AB - 1. The ventilatory response to maximal incremental exercise and the accompanying sensation of breathlessness were studied after the inhalation of 0.9% sodium chloride (saline) and 5% bupivacaine aerosols in six patients with interstitial lung disease. 2. The adequacy of airway anaesthesia induced by bupivacaine aerosol was confirmed by the absence of the cough reflex to 5% citric acid aerosol on completion of exercise. 3. All subjects first performed a trial exercise test to familiarize them with the procedure and to assess the degree of arterial oxygen desaturation on exercise. In subsequent tests, supplementary oxygen was given to maintain the saturation at 95% or above. 4. Airway anaesthesia had no effect on the ability to perform exercise as assessed by maximum workload, CO2 production or heart rate. No significant changes were seen on the pattern of breathing, minute ventilation or end-tidal PCO2 on exercise. There was, however, a small but statistically significant increase in ventilation related to CO2 production (VE/VCO2) at the end of exercise. 5. There was a tendency for breathlessness to be increased by airway anaesthesia but this did not reach statistical significance. 6. These results provide no evidence that vagal afferent activity is responsible for the abnormal ventilatory response to exercise in patients with interstitial lung disease. The perception of breathlessness in these patients was not diminished by anaesthesia of the airway. PMID- 3345637 TI - A DNA polymorphism of the apolipoprotein C-III gene in extracoronary atherosclerosis. AB - 1. A genetic polymorphism of apolipoprotein (apo) C-III was studied in 49 Caucasian patients with extracoronary atherosclerosis demonstrated by angiography. 2. Twelve patients (24%) possessed an uncommon allelic variant of the apo A-I/C-III gene cluster compared with two (4%) in 50 healthy controls (P less than 0.01). 3. Of 27 patients with carotid atherosclerosis, 22% had the uncommon genotype (P less than 0.02), and in aorto-femoral atherosclerosis (n = 22) 27% possessed the uncommon variant (P less than 0.01). 4. When normotriglyceridaemic subgroups (n = 32) with arterial disease were studied the difference in genotype frequencies persisted, 22% having the uncommon allele (P less than 0.01), suggesting that such genetic variants have effects independent of circulating levels of plasma lipids. PMID- 3345638 TI - Effects of a specific antidiuretic agonist on cardiac output and its distribution in intact and anephric dogs. AB - 1. The specific antidiuretic agonist [4-valine, 8-D-arginine]vasopressin (VDAVP) was administered intravenously to seven conscious dogs at a rate of 10 ng min-1 kg-1. Cardiac output (aortic electromagnetic flowmeter), mean arterial pressure and regional blood flows (radioactive microspheres) were measured before and after 30 min of infusion. 2. Mean arterial pressure fell from 89.9 +/- 4.5 (mean +/- SEM) to 82.3 +/- 5.9 mmHg and cardiac output increased from 115.4 +/- 8.7 to 163.0 +/- 14.4 ml min-1 kg-1. Total peripheral resistance decreased from 41.6 +/- 3.7 to 27.8 +/- 3.6 units and heart rate increased from 79.2 +/- 5.9 to 123.2 +/- 5.9 beats/min. Blood flow increased significantly in the myocardium, fat and skeletal muscle vascular bed. 3. In another group of six dogs subjected to a similar protocol 24 h after bilateral nephrectomy, mean arterial pressure fell from 102.2 +/- 5.3 to 82.7 +/- 3.4 mmHg and cardiac output increased from 125.6 +/- 3.0 to 171.2 +/- 4.0 ml min-1 kg-1. Total peripheral resistance decreased from 39.3 +/- 3.4 to 23.4 +/- 1.3 units and heart rate increased from 84 +/- 4.9 to 113.3 +/- 4.3 beats/min. The increase in cardiac output and the fall in total peripheral resistance did not differ significantly between intact and anephric dogs. Regional blood flow responses differed in some respects in the two groups studied, but there was no evidence that the vasodilatory action of VDAVP depended on the presence of the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345639 TI - Epithelial cell proliferation and intestinal absorptive function during starvation and refeeding in the rat. AB - 1. Intestinal epithelial cell production and intestinal absorption were measured in fed, starved and refed rats. 2. Four days' starvation significantly decreased the crypt cell production rate (CCPR), absorption, small intestinal length and crypt cell population. 3. There was an immediate increase in absorption 1 day after refeeding, which preceded a slower increase in CCPR. The absorption rate then decreased progressively after refeeding, and was significantly lower than control levels 1 week after refeeding. The CCPR, however, increased more gradually, reaching control levels after 2 days and then 'overshooting' control values. 4. There was no significant change in the crypt cell population immediately after refeeding; thus we propose that the initial increase in absorption on refeeding is either due to an accelerated maturation rate of the enterocytes or to the migration of enterocytes from the base of the villus to the functional zone. 5. The rapid recruitment of absorptive function appeared to be a 'one-off' event, the villus compartment then having to wait for increased cell production in the crypts to repopulate the villi. PMID- 3345640 TI - Effect of age and posture on human lymphocyte adenylate cyclase activity. AB - 1. A number of age-related changes have been reported in the catecholamine adrenoceptor-adenylate cyclase system. Most of the data available on these alterations come from resting subjects; the response to acute stress may provide additional insights into the age effect on these responses. 2. We measured supine and 10 min upright plasma noradrenaline and lymphocyte adenylate cyclase activity in ten healthy elderly subjects (age 66-80 years) and seven healthy young subjects (age 27-34 years). 3. Isoprenaline stimulation of lymphocyte adenylate cyclase activity was not significantly different between supine and upright positions or between elderly and young subjects. There was a marked increase in forskolin-stimulated adenylate cyclase activity in the upright posture in both elderly and young subjects. The increment over supine levels was 70% in the elderly (P less than 0.025) and 73% in the young (P less than 0.05). This enhanced forskolin activity was not seen in two young subjects who became syncopal. 4. These data suggest that enhanced forskolin-stimulated adenylate cyclase activity occurs after 10 min of upright posture in both elderly and young subjects, and may be relevant to immediate blood pressure regulation. We were unable to demonstrate any age-related differences in these acute adrenergic responses. PMID- 3345641 TI - The role of vasopressin in the regulation of haemostatic function in man--fact or fiction? PMID- 3345642 TI - Routine monitoring of serum vancomycin concentration: the answer lies in the middle. PMID- 3345643 TI - Effect of sucralfate on theophylline absorption in healthy volunteers. AB - The effect of oral administration of sucralfate concurrently with a single oral dose of non-sustained-release theophylline was studied in eight healthy male volunteers. A two-way, randomized, cross-over study design was used. During the control phase, each subject received a single 5-mg/kg dose of a non-sustained release theophylline product. During the treatment phase, a 1-g sucralfate tablet was ingested four times a day for two days before the theophylline dose, with the theophylline dose, and six hours after the dose. Plasma samples were collected at frequent intervals for 24 hours after theophylline dosing. Plasma theophylline concentrations, determined by high-performance liquid chromatography, were similar in the absence and presence of sucralfate. No significant differences in theophylline half-life or mean residence time between the control and treatment phases were observed. A significant decrease in the area under the plasma drug concentration-time curve was observed in the presence of sucralfate. However, the magnitude of this change was minimal and unlikely to be clinically important. In these healthy subjects, the concomitant administration of sucralfate with a single dose of non-sustained-release theophylline did not alter the rate or extent of theophylline absorption to a clinically important degree. PMID- 3345644 TI - Bromate poisoning from ingestion of professional hair-care neutralizer. PMID- 3345645 TI - Treatment of oral candidiasis with amphotericin B solution. PMID- 3345646 TI - Collagen remodelling in rat periodontal tissues: compensation for precursor reutilization confirms rapid turnover of collagen. AB - Measurement of collagen turnover is complicated by the reutilization of isotopic precursors used to label the collagen. In an earlier study a novel approach was used to circumvent the problems of precursor recycling and unusually short half lives were determined for collagen in adult rat periodontal tissues (Sodek, 1977). To verify these results we have used an alternate procedure devised by Poole (1971) in which the decay profile for the radiolabelled protein is corrected in accordance with the decay of the radiolabelled precursor. In this manner real half-lives for mature, neutral salt-insoluble collagen were determined as 3 days in the molar periodontal ligament, 6 days in the continuously erupting incisor ligament and approximately 10 days in the lamina propria of the gingiva, compared to apparent half-lives for these tissues of 6, 12 and approximately 20 days, respectively. The values calculated for actual half lives are, therefore, approximately two-fold faster than values determined without compensating for reutilization, a difference that is in agreement with other protein turnover studies in which the effects of precursor reutilization have been measured. Although the real half-lives determined in this study indicate turnover rates for the periodontal tissues that are slightly slower than reported previously, the relative differences between the tissues in the rates of collagen turnover are similar. Moreover, the study confirms the existence of a remarkably high rate of collagen remodelling in these tissues. PMID- 3345647 TI - Quantification and characterization of hyaluronic acid in different topographical areas of normal articular cartilage from dogs. AB - Normal articular cartilage from adult dogs was analyzed for hyaluronate, hexuronate and hydroxyproline. The low weight-bearing areas of both tibial plateaus and femoral condyles displayed a higher collagen content and a lower proteoglycan content than the regions of maximum contact. Both superficial and deeper layers contained more hyaluronate in areas of maximum than of minimum contact. On the other hand, in each weight-bearing area, the proportion of hyaluronate relative to total proteoglycan content appeared twice as much in the superficial layers than in their corresponding underlying zones. The molecular weight and in vitro aggregating capacity of the hyaluronate molecules were however quite similar in the different topographical areas of the articular tissue. PMID- 3345648 TI - Pseudoxanthoma elasticum (PXE): ultrastructural and biochemical study on proteoglycan and proteoglycan-associated material produced by skin fibroblasts in vitro. AB - Pseudoxanthoma elasticum is a genetic disease characterized by progressive mineralization of elastic fibers. Previous studies suggested that other components, apart from elastin, might be involved in the alterations of this connective tissue disorder (Martinez-Hernandez and Huffer, 1974; Pasquali Ronchetti et al., 1981; 1986). Evidence is presented that proteoglycan metabolism is altered in PXE-affected patient. Urinary GAGs suggests an increased degradation of glucosamine-containing GAGs in the patient. Pulse and chase experiments on in vitro skin fibroblasts indicated a decreased rate of synthesis of [35SO4] containing GAGs or an increase of their turnover rate in PXE. Moreover, when PGs produced from skin fibroblasts were identified by ultracentrifugation and gel filtration in associative conditions, PXE fibroblasts produced a significantly higher amount of the high molecular weight fraction of sulfated PGs. This high molecular weight material was present both in the medium and in the matrix and disappeared under dissociative conditions or after treatment with hyaluronidase or with pancreas elastase. By electron microscopy, PXE fibroblasts appeared to produce and secrete an enormous amount of toluidine blue 0 positive material organized as filaments and amorphous masses. These data are in agreement with previous observations of the presence of abnormal masses of microfilaments, in the dermis of PXE patients, which were sensitive to hyaluronidase and partially to trypsin and elastase (Pasquali Ronchetti et al., 1986). The results seem to confirm that at least some of the alterations of connective tissues in PXE are due to abnormal PGs metabolism and to their tendency to form abnormal aggregates in the extracellular space. PMID- 3345649 TI - Using smoothing splines to make inferences about the shape of gas-exchange curves. AB - Respiratory gas-exchange data from progressive exercise tests are typically interpreted by visual inspection. Attempts to objectify such interpretation have applied particular parametric models which limit the measures which can be studied and the inferences which can be made. We use a known spline-smoothing procedure which fits a continuous curve to such data, yielding confidence intervals for the curve and for its first and second derivatives. Rules can be made which use the derivatives to infer features of a curve's shape and to relate features from different curves in the same data set. In this way complex interpretations can be made objective, so that they may be adequately tested. PMID- 3345650 TI - Computerized stripping method for multiple nuclide microsphere studies. AB - Radiolabeled microspheres are commonly used to measure cardiac output and regional blood flow distribution in small animals such as rats. By using batches of microspheres labeled with different nuclides, several flow measurements can be made in the same animal. A protocol and computer program for analyzing data from multiple nuclide microsphere experiments are described. This protocol is designed to reduce the amount of arterial blood which must be withdrawn during microsphere distribution and eliminate the potential loss of data due to contamination of reference samples by nuclides used in previous flow measurements. PMID- 3345651 TI - A stable linear algorithm for fitting the lognormal model to survival data. AB - The lognormal model can be fitted to survival data using a stable linear algorithm. When tested on 800 sets of mathematically generated data, this method proved more stable and efficient than the iterative method of maximum likelihood, which requires initial estimates of model parameters and failed to fit a substantial fraction of data sets. Though maximum likelihood yielded more consistent estimates of proportion cured, mean, and standard deviation of log(survival time), the linear normal algorithm may nevertheless prove useful for these purposes: (i) computing initial estimates of model parameters for the maximum likelihood method; (ii) fitting data sets that cannot be fit by this method; and (iii) deriving the lognormal model directly from cumulative mortality. PMID- 3345652 TI - Computational implementation of the conditional logistic regression model in the analysis of epidemiologic matched studies. AB - Adaptation of a BMDP packaged program for the proportional hazards survival models to the analysis of an epidemiologic matched study is discussed and illustrated with numerical examples. PMID- 3345653 TI - Prolog-based system for nursing staff scheduling implemented on a personal computer. AB - An approach to the problem of nursing staff scheduling in a hospital is presented. For scheduling nurses, a variety of requirements with varied levels of significance has to be taken into account simultaneously. Because of the nature of the problem, where it is difficult to define what is the optimal solution in a strict sense, we aimed at automating scheduling by following the manual method in a faithful manner. A system for nurse scheduling has been implemented on a personal computer using Prolog. It determines favorable shift assignments on a day-to-day basis, referring to the information accumulated in the data base. In Prolog, various requirements can be expressed with relative ease, and the process of the manual method can be incorporated into the system in a natural way. The computer simulation has been conducted to test the system performance, and the obtained results demonstrated the validity of the approach. PMID- 3345654 TI - Relation between age, education, and time to respond to questions in a computer based medical interview. AB - The time required for 458 women volunteers to respond to questions in a computer based medical interview was related both to their age and to their formal education. When the analysis was restricted to the 220 women with a college degree, older women responded more slowly than their younger counterparts, and when the analysis was restricted to the 265 women between 18 and 30 years of age, women with less formal education took longer to respond. By contrast, the time required for the volunteers to record their responses was related only to age. PMID- 3345655 TI - Computer system for quantitative evaluation of an electrotactile vocoder for artificial hearing. AB - A computer-controlled experimental electrotactile vocoder system is designed to evaluate quantitatively the transmission of speech information and to test various design options for tactual vocoders. The system is composed of a digital speech synthesizer, a digital vocoder, a computer-driven electrotactile display, and an adaptive controller for psychophysical experimentation. Samples of continua representing speech contrast types occurring in natural languages are synthesized by systematically manipulating selected subphonemic features. The synthesized speech stimuli are processed using a programmable vocoder and presented to the skin with an electrotactile display belt worn on the abdomen. Transmission of significant speech parameters is quantitatively evaluated using adaptive psychophysical techniques and labeling tests. The system is used to assess the potential of speech transmission through the skin and to evaluate different vocoder configurations and processing techniques for tactual vocoders to be used as artificial hearing devices by the deaf. PMID- 3345656 TI - PITMAN: a FORTRAN program for exact randomization tests. AB - PITMAN performs exact randomization tests. It also performs Wilcoxon signed-rank tests and Wilcoxon-Mann-Whitney U tests in the presence of an arbitrary number of ties in the data. PITMAN requires an IBM PC with 256K of memory. The source code is available for those who wish to compile smaller or larger versions or wish to move PITMAN to another computer. PMID- 3345657 TI - Large lung opacity in a 52-year-old man with metastatic colon carcinoma. PMID- 3345658 TI - Epilepsy and the law. PMID- 3345659 TI - Make the schools smoke-free. PMID- 3345660 TI - Medical articles. PMID- 3345661 TI - Reflections on medicine. Would you choose another decade? PMID- 3345662 TI - Lymphadenopathy with sulindac therapy. PMID- 3345663 TI - Driving and epilepsy. The case for reform in Connecticut. PMID- 3345664 TI - Cardiac rhabdomyosarcoma. PMID- 3345665 TI - Primary tracheal carcinoma presenting with acute respiratory failure. PMID- 3345666 TI - Animal models in chronic renal failure. International Workshop on Animal Models for the Assessment of the Effects of Conservative Treatment in Chronic Renal Failure. Heidelberg, January 29-30, 1987. Proceedings. PMID- 3345667 TI - Effect of dietary phosphorus on the prevention of the progressive nephropathy following subtotal nephrectomy in male adult rats. PMID- 3345668 TI - Influence of amino acid and keto acid supplements on hyperfiltration in uremic rats. PMID- 3345669 TI - Influence of soya protein on the natural history of a remnant kidney model in the rat. PMID- 3345670 TI - Osteodystrophy in experimental uremia. PMID- 3345671 TI - Renal bone disease in chronic uremic rats. PMID- 3345672 TI - Efficacy and side effects of erythropoietin used in the treatment of anemia of uremic rats. PMID- 3345673 TI - Five-sixths nephrectomy and extracorporeal detoxification in the conscious rat. PMID- 3345674 TI - Partial nephrectomy and chronic renal failure: the 'adult' rat model. PMID- 3345675 TI - Partial nephrectomy and chronic renal failure: the 'mature' rat model. PMID- 3345676 TI - Acute renal failure after 5/6 nephrectomy: histological and functional changes. PMID- 3345677 TI - Natural course of the development of histological lesions after 5/6 nephrectomy. PMID- 3345678 TI - Low-protein diet prevents glomerular damage in experimental nephrosis. PMID- 3345679 TI - Is there a surgical personality? PMID- 3345680 TI - Gastrin stimulates intestinal potassium absorption. PMID- 3345681 TI - Gastric injury induced by water immersion stress: prevention by prostaglandin and the role of glutathione. PMID- 3345682 TI - Endothelial permeability to iodine-125-labeled albumin predicts skeletal muscle injury after ischemia reperfusion. PMID- 3345683 TI - Maintenance of cardiac glutathione levels after cold ischemia. PMID- 3345685 TI - Bilateral extensive xanthelasma palpebrarum. AB - A case of xanthelasma palpebrarum with extensive and disfiguring involvement of all four eyelids in a patient without abnormal serum lipid levels is reported. PMID- 3345684 TI - Xanthoderma: case report and differential diagnosis. AB - There are many possible causes of yellow-orange discoloration of the skin. It is important to ascertain the presence or absence of scleral icterus in determining the diagnosis. Yellow sclerae are found in patients with all causes of hyperbilirubinemia due to the predilection of bilirubin for elastic tissue. The sclerae are also involved in the staining due to some drugs such as quinacrine. Hypercarotenemia, lycopenemia, and riboflavinemia do not involve the sclerae. In our case there are several possible causes for yellow-orange pigmentation of the skin. The patient had malaria, as well as a history of hepatitis, both of which could have resulted in hyperbilirubinemia. However, a bilirubin level of 1.2 mg/100 ml was not sufficient to result in jaundice. The most important finding was that his sclerae were uninvolved, leading us to consider other causes of yellow-orange coloration. The localization of the pigment to the palms and soles is consistent clinically with the diagnosis of hypercarotenemia. This was verified by a serum beta-carotene level slightly above normal. In this case, the carotenemia was due to the ingestion of red palm oil, which the patient had consumed in great quantities while living in Liberia. The surprisingly low level of serum beta-carotene is explained by the fact that he had not consumed red palm oil or another concentrated source of carotene for about three months since living in the United States. Due to the lipophilic nature of the carotenoids, sufficient amounts remained in the tissue to produce discoloration for up to five months, regardless of serum levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345686 TI - Use of a support group for dermatologic patients. AB - Hospital nurses led weekly group sessions to provide dermatologic inpatients a supportive climate in which to share common concerns about skin disease and a forum for dissemination of dermatologic information. Session leaders kept a journal, noting themes and group dynamic patterns for each meeting. Participants also responded to a session evaluation questionnaire. Data from the journal and questionnaires were collected for one year to describe the issues and concerns raised in a support group for dermatologic patients and to assess the effectiveness of this approach in overall patient management. Three themes were consistently discussed: problems with stress, self-esteem, and social interaction; concerns with medical treatment; and coping with loss. Participants indicated that support and encouragement had been given and received. Need for a dermatologic patient support group was demonstrated. Location of such a group in an outpatient day-care setting was recommended. PMID- 3345687 TI - Hymenoptera stings. PMID- 3345688 TI - Necrotizing sialometaplasia. AB - A case of necrotizing sialometaplasia in a 29-year-old man is reported. Characterized by large, deep, well-demarcated ulcerations on the hard palate and other areas where salivary gland tissue is found, the condition is benign and resolves spontaneously. The cause is believed to be infarctive. PMID- 3345689 TI - Snake bite. PMID- 3345690 TI - Mediators of inflammatory bowel disease. Proceedings of a symposium. Los Angeles, California, March 4, 1987. PMID- 3345691 TI - Mediators of inflammation in inflammatory bowel disease. PMID- 3345692 TI - Hypoglycemia and counterregulation. PMID- 3345693 TI - [Are filiform fibromas of the skin a marker for colonic neoplasia?]. AB - 750 consecutive out-patients undergoing diagnosis for possible disease of the colon but no history of colon neoplasia were examined for skin tags (achrocordons). They were found in 257 patients, in 30 as multiple (greater than five) lesions. Benign adenoma of the colon was found with similar frequency in patients with (27.6%) and without (22.1%) tags. However, colon carcinoma was twice as frequent in patients with skin tags (8.2%) than controls (4.1%). Patients with multiple tags had an even higher risk of colon carcinoma (odds ratio 7.8; 95% confidence limits 2.2-24.4; P less than 0.01) and a slightly increased risk of benign colon adenoma (odds ratio 2.4; 95% confidence limits 0.9 6.0; P less than 0.05). Whether this association is important in the diagnosis of colon tumours should be tested further by investigating healthy subjects with skin tags. PMID- 3345694 TI - [Cumulative functional rates of orthoptic dialysis fistulas and interposition grafts]. AB - The function of 221 dialysis shunts was investigated retrospectively in 111 patients of an outpatient haemodialysis centre. The mean age of the patients was 58 years. Of 221 recorded shunts, 171 were direct arteriovenous fistulas, while 50 were interposition grafts. The longest observation period was almost 20 years (227 months). The cumulative function rate was evaluated by the life table method; primary patency (until first revision) was differentiated from total function (revisions included). The direct fistulas as compared to the grafts had a significantly (P less than 0.05) higher primary function rate (median 35 vs. 13 months) and after 36 months also a significantly longer total function (median 76 vs. 28 months). Complications were significantly (P less than 0.05) more frequent in grafts than in fistulas (61/50 vs 120/171). Surgical revisions of fistulas failed significantly more often (P less than 0.05) than revisions of grafts (137/171 versus 26/50). Grafts on the forearm had significantly worse results as compared to grafts or fistulas on the upper arm (P = 0.03). In contrast to age, sex and underlying disease of patients a blood pressure less than 130/70 mmHg was a significant risk factor for shunt failure (P = 0.002). Analysis of primary function shows (clearer than the total patency rate) that a direct fistula is a better vascular access in haemodialysis patients than a graft. PMID- 3345696 TI - [Stridor due to bolus obstruction of the esophagus]. AB - Obstruction of the oesophagus by a piece of goulash meat resulted in tracheal stenosis in an 18-year-old girl. Because of the history of the illness and information supplied by others, as well as the marked stridor, it was first thought that the tracheal stenosis was at the level of a previous tracheostomy with aspiration, but bronchoscopy revealed marked bulging of the posterior wall of the trachea. Subsequent oesophagoscopy then detected the foreign body, which was removed whole. PMID- 3345695 TI - [Riedel's struma and fibrous mediastinitis. Positive therapeutic responsiveness to corticoids]. AB - In a 45-year-old man with chronic hepatitis B a fibrous mediastinitis developed originating from a Riedel's thyroiditis. Because of associated pleural effusion compression of a pulmonary vessel could not be excluded. Administration of corticoids, undertaken in the absence of general guidelines to treat the mediastinitis, achieved regression of the pleural effusion and the mediastinal changes, as well as shrinkage of the cervical fibrosis. PMID- 3345697 TI - [Efficient lung function tests]. PMID- 3345698 TI - [Responsibility of hospital physicians and the hospital administrator in personnel shortages]. PMID- 3345699 TI - [Issuing of certificates by hospital physicians as a service responsibility]. PMID- 3345700 TI - [Diagnosis of sarcoidosis]. PMID- 3345701 TI - [Hemoglobin A1 in kidney failure]. PMID- 3345702 TI - [Migraine and thrombocytopenia]. PMID- 3345703 TI - [Uremic hyperphosphatemia]. PMID- 3345704 TI - An analysis of potential biases in the loss of indigent infants to follow-up. AB - Loss to follow-up is a major problem in indigent inner-city populations. We evaluated a large, well-described, inborn indigent population of high-risk infants (HRI) and control infants (CI) to assess possible selection biases in loss to follow-up at one year adjusted age. Serial clinic visits, phone calls, and letters and payment of $20.00 for attending at 1 year was used to minimize patient loss. Yet, the 1 year loss rate was high, and among HRI, greater for ventilator-treated infants greater than 1500 g birthweight (71/114; 62%) than for ventilator-treated very-low-birthweight (VLBW; less than 1500 g) infants (39/108; 36%) or non-ventilated VLBW infants (62/145; 43%) (P less than 0.05). Multivariate analyses indicated that those lost to follow-up were at no greater risk of a poor outcome on the basis of prenatal and perinatal medical and socioeconomic findings than were those in the same risk group (HRI or CI) or subgroup of HRI who were examined at 1 year. In a review of hospital records, similar rates of hospitalization and neurologic problems during infancy were identified for HRI examined and HRI lost to follow-up. The identification of such morbidity during infancy may be less complete for HRI lost to follow-up than for those examined. Thus, the high frequency of deficits observed in follow-up evaluation of indigent HRI is unlikely to result from loss of unaffected infants. PMID- 3345705 TI - Does gastric acid protect the preterm infant from bacteria in unheated human milk? AB - Although preterm mother's milk has greater nutritional and anti-infective properties than donor milk, it may be highly contaminated with bacteria. We therefore asked three questions: what is the fate of these bacteria in the preterm infant's stomach, is gastric pH important, and what factors affect gastric pH? pH, colony count and bacterial identification were performed on the milk and on serial gastric aspirates in 20 preterm infants on 25 occasions. Seventeen milk samples grew bacteria, five potentially pathogenic and 12 non pathogenic. Twelve of 25 prefeeding gastric samples were sterile, but following the feeding all the samples grew non-pathogenic bacteria and 70% grew potential pathogens. With time pH decreased and by 2-h samples with pH less than 3.5 had no bacterial growth; Candida albicans still flourished in a low pH (mean 2.8). We concluded that a low gastric pH may be more important than the bacterial count of the milk. In a second study, 91 serial gastric pH measurements were made on 12 preterm infants. pH tended to decrease with increasing age and was significantly lower in infants fed exclusively human milk (2.7 vs. 3.6; human milk versus formula P less than 0.02) We speculate that human milk may influence gastric acid production and thus protect the preterm infant from bacteria in the milk. PMID- 3345706 TI - Transcutaneous PO2, PCO2 and heart rate patterns during normal postnatal adaptation and respiratory distress. AB - Three groups of neonates were observed during their first 5 days of postnatal life. Healthy term babies (N = 22) did not differ in their heart rate variability (HRV) nor heart rate (HR) from the healthy preterm babies (N = 21) during the first 3 days. On day 5 beat-to-beat variability of term babies was greater. In healthy term and preterm infants HRV increased between days 1 and 3. HRV of the babies with respiratory distress syndrome (RDS) (N = 1) remained low throughout the study period. HR of the babies with RDS was significantly higher compared to the other groups on the days 1 and 3. Transcutaneous PO2 was high in healthy preterm infants compared to the other groups. The correlation between PaCO2 and PtcO2 in RDS was insufficient to make clinical judgement. PtcCO2 of all neonates tended to rise on the day 5 but the rise was most prominent in the infants with RDS. The correlation of PaCO2 and PtcCO2 was good. In RDS high HR, low HRV and elevated PtcCO2 were the typical findings and present throughout the study period. PMID- 3345707 TI - Vocal communication between parents and infants. AB - Mothers and fathers of 20 boys and 20 girls representing all social classes were filmed when playing with their 6-month-old infants in a standardized playing situation. The vocal behavior of the parents and their infants was analyzed for sex differences. In addition, vocal activity was compared in parents and infants. Mothers showed a higher vocal activity than fathers together with their infants. Mothers also received more vocal activity from their infants than the fathers did. Fathers took more vocal initiatives towards girls than towards boys. Parents were vocally more active than infants. Comparing the vocal irritability of boys and girls, no differences were found. Fathers and mothers did not differ in vocal responsiveness to vocal irritability. Girls received more vocal initiations from fathers than boys while mothers treated boys and girls vocally equally. PMID- 3345708 TI - Assessment of elastin maturation by radioimmunoassay of desmosine in the developing human lung. AB - Desmosine has been quantitated in the normally grown fetal and early infant lung by radioimmunoassay. Desmosine could first be detected at 22 weeks gestation: the concentration of desmosine expressed per milligram lung DNA increased in approximately linear form up to about 55 weeks postconceptional age. The concentration in peripheral lung was approximately half that in whole lung homogenates. Lungs of infants dying with acute HMD and lungs of growth retarded infants showed no significant differences from the normals, although there was a tendency for higher desmosine concentrations in prematurely born growth retarded infants. PMID- 3345710 TI - Ophthalmologic emergencies and ocular trauma. PMID- 3345709 TI - Sucking behaviour and milk intake in jaundiced neonates. AB - Twenty seven healthy newborn infants who developed hyperbilirubinaemia during the first week of life were investigated by daily test feeds between the second and sixth days of life. Nutritive sucking was assessed by measurement of rate, duration and pressure of sucking and by clinical observation. Milk consumption, duration and pressure of sucking all showed a significant increase during the period of study. Sucking rate did not vary with age. Significant correlation of sucking time and sucking pressure with milk intake were observed. Serum bilirubin levels showed no correlation with milk consumption on each day of the study or with the pooled data of feeding parameters when compared independently of post natal age. Hyperbilirubinaemia was significantly correlated with the infants who appeared disinterested in feeds when assessed by clinical observations of apparent hunger and alertness at the onset of the test feed. However, milk intake was not impaired in these infants. PMID- 3345711 TI - Ocular examination. AB - In ophthalmologic emergencies, the ocular examination should proceed as any other organ system might, namely, as an orderly evaluation of that system. The history and subsequent examination can be conducted in simple phrases, with the patient telling his or her story. The nonspecialist need not fear an ocular injury or emergency any more than any other in the Emergency Department. PMID- 3345712 TI - Formulary of commonly used ophthalmologic medications. AB - This brief article presents in table form the most commonly used ophthalmologic agents. Other information pertinent to these agents is included, such as how the medication is supplied, what are the adverse effects, the usual dosages, and the most probable use for each agent. PMID- 3345713 TI - Hormonal regulation of growth hormone secretion and messenger ribonucleic acid accumulation in cultured bovine pituitary cells. AB - In both primary cultures and transformed tumor cultures of rat pituitary cells, preincubation with T3 or dexamethasone increases GH secretion, mRNA accumulation, and gene transcription. GRF stimulates secretion and transcription in primary rat pituitary cultures. Sex steroids stimulate GH secretion in man, but contradictory findings have been reported in vitro. We studied the hormonal regulation of bovine GH (bGH) in primary monolayer cultures of adult bovine pituitaries. Neither T3 nor dexamethasone changed immunoreactive bGH secretion during a 3-h experimental incubation. After 72-h preincubation with T3 or dexamethasone, bGH secretion remained unchanged. T3 (10(-8) M) or dexamethasone (10(-8) M) did not alter the bGH secretory response to doses of GRF from 10(-12)-10(-8) M. However, T3 (P less than 0.001; r = 0.73) and dexamethasone (P less than 0.001; r = -0.71) decreased bGH mRNA content in dose-dependent fashions, as determined by Northern analysis and RNA dot blots probed with 32P-labeled bGH cDNA. T3 10(-7) M) decreased bGH mRNA content to 70% of the control value, 10(-7) M dexamethasone decreased bGH mRNA content to 77% of the control value, while GRF increased bGH mRNA content to 174% of the control value in a dose-dependent fashion (P less than 0.001; r = 0.72). Preincubation with testosterone or dihydrotestosterone did not change basal or GRF-stimulated GH secretion. Seventy-two-hour preincubation with 10(-8) M estradiol did not alter basal GH secretion, but increased the bGH secretory response to doses of GRF from 10(-11)-10(-8) M (P less than 0.001). Incubation with estradiol did not change bGH mRNA levels. These results demonstrate that, in contrast to rat GH mRNA, bGH mRNA accumulation is inhibited by T3 and dexamethasone. Estradiol augments the response to GRF, but this effect is not mediated by an increase in mRNA content. The hormonal responses of somatotropes vary significantly among mammalian species. PMID- 3345714 TI - Acute down-regulation of the somatogenic receptors in rat liver by a single injection of growth hormone. AB - Prolonged continuous administration of GH induces somatogenic receptors in rat liver. However, because GH secretion is pulsatile and the effect of acute changes in serum GH concentrations on liver GH receptors is unknown, we measured total (MgCl2-treated homogenates) and free (water-treated homogenates) GH-binding sites in the livers of hypophysectomized (hypox) rats killed between 1 and 24 h after a single sc injection of rat GH (100 micrograms/100 g BW; n = 29). Control hypox rats (n = 10) were studied immediately or 3 h after injection of vehicle. GH injection caused profound decreases in both total and free liver GH receptors, but these changes followed different kinetic patterns. Free receptors declined rapidly (to 17% of control), reaching a nadir at the same time (1 h) as the maximal GH concentration in serum. These free receptors then increased, returning to normal 12 h after GH injection. In contrast, total GH receptors were slightly increased at 1 h, decreased to their minimal value at 6 h (53% of control), and returned to normal at 12 h. Serum immunoreactive somatomedin-C/insulin-like growth factor I concentrations peaked 12 h after GH injection. Total and free liver GH receptors were quantitated in hypox rats that had been injected 3 h previously with doses of rat GH from 2.5-500 micrograms/100 g BW or with vehicle. Both total and free binding sites decreased in a dose-dependent manner; the maximal responses were 40% and 90% below control values, respectively. Half maximal reductions in GH binding were achieved when 10 micrograms GH/100 g BW were given. These data suggest that a surge of GH in serum leads to a time- and dose-dependent down-regulation of the liver somatogenic binding sites and are consistent with ligand-induced internalization and degradation of the receptor. PMID- 3345715 TI - Electron microscope radioautographic evidence of in vivo androgen-binding protein internalization in the rat epididymis principal cells. AB - The androgen-binding protein (ABP) has been purified from rat testes with a yield of 14% using four steps of HPLC and was subsequently iodinated to a specific activity of 0.1 mCi/mg protein. Using a micromanipulator, [125I] iodo-ABP dihydrotestosterone was injected intraluminally into the proximal caput of the rat epididymis. Epididymides were sampled from 3 to 120 min after the injection of the tracer and processed for transmission electron microscopy autoradiography. Our results showed the accumulation of detectable radioactive sources in the apical cytoplasm of only one of the epithelial cell type lining the ductus, the principal cells. In the interval from 3 to 120 min, the iodinated ABP was mainly present in the supranuclear region and was especially concentrated over coated structures, endosomes, multivesicular bodies, and over the Golgi apparatus. The same pattern was obtained using [3H]dihydrotestosterone-ABP complex instead of iodinated ABP. In addition, there was a negative correlation between the log time and the distribution of the silver grains in the luminal border and in the compartment of the apical vesicles. On the contrary, there was a positive correlation between the log time and the distribution of the silver grains in the Golgi apparatus. These results provide, for the first time, direct histological evidence of the in vivo ABP internalization by the principal cells. Since horseradish peroxidase, a fluid-phase endocytosis marker, when injected under the same conditions was internalized in both apical and principal cells, since labeled radioactive ABP appeared to be bound to the membrane of the endocytic apparatus rather than to its content, and since this binding and uptake could be prevented in the presence of an excess of unlabeled ABP, it is concluded that the internalization of ABP could not be a nonspecific fluid-phase endocytosis but should be dependent on its interaction with the apical plasma membrane of the principal cell. It still remains to be determined if these mechanisms involve the binding of ABP to a specific membrane receptor. PMID- 3345716 TI - Changes in brain aromatase and 5 alpha-reductase activities correlate significantly with seasonal reproductive cycles in goldfish (Carassius auratus). AB - Aromatization and 5 alpha-reduction are known to be required for the full expression of testosterone actions in neuroendocrine tissues. Although aromatase and 5 alpha-reductase activities in brain and pituitary can be experimentally manipulated by castration and steroid replacement, naturally occurring variations during seasonal reproductive cycles have not been examined in any species. Goldfish (Carassius auratus) were selected for study because they exhibit exceptionally high levels of aromatase in both brain and pituitary, although 5 alpha-reductase levels resemble the vertebrate norm. Four animals of each sex were tested monthly through three breeding seasons (2.5 yr). Using previously validated techniques, the enzymes were assayed by product formation from [3H]androstenedione in homogenates of anterior hypothalamus-preoptic area (AHPOA), remaining telencephalon (TEL), whole pituitary, ovary, and testis. Seasonal variations in aromatase were most dramatic in the AHPOA of female fish, exhibiting a peak in April and May that was 6-fold higher than the nadir in July. As judged by changes in the appearance and weight of the gonads, maximal aromatase coincided with the spawning season, whereas low enzyme levels corresponded to reproductive inactivity. Seasonal variations were similar but of a lesser magnitude in the TEL of females and in the AHPOA and TEL of males (2- to 3-fold, peak to nadir). Both ovarian and testicular aromatase showed cyclic changes; however, activity was much lower than that in brain at all times of the year (4.5, 1.2, and 47.0 pmol/mg protein, maximal values in ovaries, testes, and AHPOA, respectively). Pituitary aromatase varied from 5-22 pmol/mg protein, but was not consistently correlated with season. Cyclic changes in 5 alpha-reductase were distinctly different from those in aromatase, with maximal values in both brain and pituitary occurring when fish were reproductively inactive. In general, circulating sex steroids were high when aromatase was high and low when reductase was maximal; however, there was no apparent causal relationship suggested by temporal changes in a given steroid. Variations in testosterone metabolism, by regulating the quantity and quality of active hormone in close proximity to receptor sites, may be responsible for the changes in feedback sensitivity and behavioral responsiveness that are known to occur in seasonal breeders. PMID- 3345717 TI - Hepatic placental lactogen receptors during pregnancy in the mouse. AB - The binding sites for mouse placental lactogen-II (mPL-II) in virgin and pregnant mouse hepatic membranes were analyzed by Scatchard analysis and affinity cross linking. Competitive binding studies showed that mPL-II and mouse PRL (mPRL) bound to the same receptors in all liver membrane preparations, although the affinity of mPRL binding was lower than that of mPL-II binding. Two classes of receptors for mPL-II, high and low affinity, were found by Scatchard analysis. The concentration of both types of sites in liver membranes increased during pregnancy. In contrast, the affinity of both sites for mPL-II was highest in virgin female mice and declined during pregnancy. Cross-linking of [125I]iodo-mPL II to maternal liver membranes resulted in the specific labeling of one major protein species of 67,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions. Under nonreducing conditions, two bands of approximately 63,000 and 60,000 daltons were apparent. Subtraction of the mol wt of mPL-II (22,000, reduced; 20,000, nonreduced) from the mol wt of the cross-linked complex indicated that the mol wt of the receptor was 45,000 under reducing conditions and 43,000 and 40,000 under nonreducing conditions. These observations suggest that mPL-II receptors may be present in mouse liver membranes in at least two forms. PMID- 3345718 TI - Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. AB - We developed a mouse bone marrow culture system to examine the process of osteoclast-like multinucleated cell formation from its progenitors. When mouse marrow cells were cultured for 8 days with 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3, 10(-10) to 10(-7) M] or human PTH (1-34) (25-100 ng/ml), tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells formed. No TRACP-positive multinucleated cells appeared in the absence of these hormones. 1 alpha,25-(OH)2D3 and PTH also increased the number of the clusters of TRACP positive mononuclear cells. Time course studies showed that these TRACP-positive mononuclear cell clusters appeared before the formation of TRACP-positive multinucleated cells, suggesting that the TRACP-positive mononuclear cells are precursors of the multinucleated cells. Salmon calcitonin markedly inhibited the formation of TRACP-positive multinucleated cells but not TRACP-positive mononuclear cell clusters induced by 1 alpha,25-(OH)2D3 or PTH. TRACP-positive mononuclear cells and multinucleated cells were rarely stained for nonspecific esterase, but some mononuclear cells were positively stained for both nonspecific esterase and TRACP. More that 90% of the TRACP-positive mononuclear cell clusters and multinucleated cells were found near colonies of alkaline phosphatase positive mononuclear cells (possibly osteoblasts). When marrow mononuclear cells were cultured on sperm whale dentine slices in the presence of 1 alpha,25-(OH)2D3 or PTH, numerous resorption lacunae were formed. These results suggest that 1) TRACP-positive multinucleated cells formed in response to osteotropic hormones in mouse marrow cultures satisfy most of the criteria of osteoclasts, and 2) osteoblasts may play an important role in osteoclast formation. PMID- 3345719 TI - Stimulation of in vitro triglyceride synthesis in the rat hepatocyte by growth hormone treatment in vivo. AB - Hepatic fatty acid metabolism in the rat is sexually differentiated. Rates of esterification by the liver of fatty acid into triglyceride and other esterification products (phospholipid, diglyceride, cholesteryl esters) are higher in the female than in the male. There is evidence to suggest that GH feminizes other hepatic systems that exhibit sexual dimorphism, including hepatic steroid metabolism, PRL receptors, and estrogen binding. To investigate the role of GH in maintenance of the high rates of fatty acid esterification observed in the female, we assessed rates of [1-14C]oleic acid utilization by hepatocytes prepared from hypophysectomized (hypox) cortisol/T3-replaced female rats with an without continuous in vivo infusion of human (h) GH (5 micrograms/h). In addition, we assessed the effect of in vivo hGH treatment (5 micrograms/h) on [1 14C]oleic acid utilization in the normal male rat. Hypophysectomy was accompanied by a reduction in incorporation of [1-14C]oleic acid into products of esterification (triglyceride, phospholipid, diglyceride) and oxidation (CO2, ketone bodies). Continuous infusion of hGH (5 micrograms/h; 14 days) restored rates of fatty acid esterification in the hypox-cortisol/T3-replaced female rat, with the exception of cholesteryl esters. hGH infusion partially restored rates of fatty acid oxidation in the hypox cortisol/T3-replaced female rat. Treatment of the adult male rat with continuous infusion of hGH (5 micrograms/h; 7 days) resulted in increased rates of incorporation of [1-14C] oleic acid into triglyceride. In contrast, incorporation of oleic acid into phospholipid, diglyceride, and cholesteryl esters was unaltered. These results suggest that GH may be an important regulator of hepatic fatty acid metabolism. PMID- 3345720 TI - Ligand interaction at the estrogen receptor to program antiestrogen action: a study with nonsteroidal compounds in vitro. AB - The estrogenic and antiestrogenic actions of the geometric isomers of tamoxifen and 4-hydroxytamoxifen were determined in a PRL synthesis assay using primary cultures of dispersed immature rat pituitary gland cells. 4-Hydroxytamoxifen was 100 times more potent as an antiestrogen than tamoxifen. The cis isomer of tamoxifen was a weak estrogen, but the cis isomer of 4-hydroxytamoxifen was converted to the trans isomer during the 6-day assay. This made an accurate determination of the properties of cis-(E)4-hydroxytamoxifen impossible. A series of fixed ring derivatives of the compounds were evaluated in the PRL synthesis assay in vitro to determine their estrogenic and antiestrogenic activities. The fixed ring derivatives of tamoxifen, cis-tamoxifen and trans-(Z)4 hydroxytamoxifen all had properties that were the same as those of the original triphenylethylenes. The fixed ring derivative of the cis-(E) isomer of 4 hydroxytamoxifen was a weak competitive antagonist of estrogen action with only very slight estrogenic properties. This contrasted with the other cis isomers of triphenylethylenes. We propose that the hydroxyl group on the molecule may orient the ligand at the binding site of the estrogen receptor to place the alkylaminoethoxy side-chain in a position to produce antiestrogen action. PMID- 3345721 TI - Estrous cycle- and pregnancy-related differences in expression of the proenkephalin and proopiomelanocortin genes in the ovary and uterus. AB - Expression of the genes for two opioid peptide precursors, proenkephalin and POMC, was examined within the female reproductive system of rodents as a function of the estrous cycle and during pregnancy. Proenkephalin RNA was found to change markedly during the estrous cycle in both the ovary and uterus (approximately 6- and 3-fold, respectively). The highest concentrations occurred at estrus in the rat ovary and at metestrus and diestrus in the rat uterus. In sharp contrast to proenkephalin RNA, the abundance of POMC RNA remained relatively constant throughout the estrous cycle in both tissues. Similar results were obtained in the cycling hamster ovary. During pregnancy, the concentrations of proenkephalin RNA in the rat ovary showed little variation, while in the uterus a 4-fold increase in this transcript was observed. The effects of pregnancy on POMC RNA were the reverse of this pattern; its abundance increased 2-fold in the ovary and did not vary substantially in the uterus. These differences in the expression of proenkephalin and POMC genes during the estrous cycle and pregnancy suggest that these two opioid peptide precursors are associated with distinct functional roles within the female reproductive system. PMID- 3345722 TI - The heterogeneity of circulating human serum erythropoietin. AB - The presence of more than one form of immunoreactive erythropoietin was suggested by discrepancies between the levels of immunologically detectable and biologically active erythropoietin in the sera of normal individuals and patients with end-stage renal disease. In both groups, the level of immunologically detectable hormone was significantly higher than that of bioactive hormone. Sera from end-stage renal disease patients and normal subjects were fractionated on a gel permeation column, and the immunoreactive erythropoietin in the fractions was measured by RIA. Three classes of immunoreactive erythropoietin were found in the sera: one eluting before the [125I]erythropoietin marker, one coinciding with the [125I]erythropoietin marker, and a third eluting after the labeled tracer in the region of the cytochrome c marker. The high and low mol wt components were more immunoreactive than the human urinary erythropoietin standard in the RIA. Biological activity, as determined in the in vitro rat bone marrow assay, was found only in the material eluting with the erythropoietin tracer. These studies show that immunoreactive erythropoietin in the serum consists of three components with different immunoreactivities: high and low mol wt components and a component with a mol wt similar to that of the native hormone. PMID- 3345723 TI - Stimulation and inhibition of pituitary growth hormone release by angiotensin II in vitro. AB - Rat pituitary cell aggregates cultured in serum-free chemically defined medium, single cells, and hemipituitaries were used in a perifusion system to study the influence of angiotensin II (AII) on GH release. In aggregates the peptide displayed both stimulatory and inhibitory effects on GH release, depending on the hormonal conditions of the culture medium and the age of the animal. When cultured in the absence of glucocorticoid, a modest but statistically significant stimulation was seen in aggregates from immature as well as adult animals. In aggregates from 5-day-old animals, dexamethasone (DEX) strongly enhanced the GH releasing activity of AII in a dose-dependent way; in aggregates from 14- and 25 day-old rats, the same pattern was found, although the stimulatory action was weaker than the effect in 5-day-old rats. In aggregates from adult animals, the glucocorticoid established an inhibitory effect of AII on GH release, an effect seen with both low and high concentrations of DEX. These age- and DEX-dependent effects were not found for AII stimulation of PRL release. In the presence of DEX, AII also inhibited GRF-induced GH release in aggregates from adult animals, while it was synergistic with GRF in aggregates from developing animals. The effects of AII on GH release disappeared when aggregates were redispersed into single cells. However, in these single cell preparations AII strongly stimulated PRL release. In hemipituitaries from 1-, 5-, and 14-day-old animals, AII also stimulated GH release, but no effect was seen in hemipituitaries from 25-day-old and adult animals. These data indicate that AII has dual effects on GH release depending on the developmental stage of the animal and the hormonal environment. Furthermore, since no effect of AII was seen after redispersion of aggregates into single cells, both stimulatory and inhibitory effects seem to be based on an intercellular signaling system. PMID- 3345724 TI - Regulation of insulin-like growth factor messenger ribonucleic acid in rat growth plate by growth hormone. AB - The mechanism of action for the stimulatory effect of GH on longitudinal bone growth is not yet clarified. Several recent reports indicate that GH has a direct effect at the site of the epiphyseal growth plate, as opposed to the somatomedin hypothesis which holds that the effect of GH is mediated by circulating insulin like growth factors (IGFs). Using a RNA probe in a solution hybridization assay we investigated the presence of IGF-I mRNA in rat rib growth plate. Hypophysectomy resulted in a decrease in the number of IGF-I mRNA copies compared to that in normal rats. Replacement treatment with GH restored the number of transcripts in a specific and dose-dependent manner. The results show that GH regulates the level of IGF-I mRNA in rat rib growth plate and give further support to the hypothesis that locally produced IGF-I might contribute to the stimulatory effect of GH on longitudinal bone growth. PMID- 3345725 TI - Transfer of thyroxine from the mother to the rat fetus near term: effects on brain 3,5,3'-triiodothyronine deficiency. AB - It has recently been shown that thyroid hormones are transferred from the mother to the developing rat embryo early in gestation, before the onset of fetal thyroid function. We have now studied whether there is transfer of T4 from the mother to the fetus late in gestation when the fetal thyroid is impaired. Normal and thyroidectomized females were mated, given a goitrogen [methimazole (MMI)], starting before the onset of fetal thyroid function and until term, alone or together with a constant infusion of T4 (1.8 micrograms/100 g BW.day). T4 and T3 were determined by RIA in several maternal samples and in tissues from 21-day-old fetuses. The administration of MMI blocked the fetal thyroid, as assessed from the decreased thyroid concentrations of T4 and T3. The concentrations of both iodothyronines also decreased in placenta, thyroid, plasma, brain, liver, lung, and carcass of fetuses from MMI-treated dams. Infusion of T4 into such MMI treated mothers partly avoided this decrease, and T4 levels increased in all fetal tissues to 41-57% of those in normal fetuses. In contrast to this, T4 infusion affected the concentration of T3 to varying degrees in different tissues. The T3 concentration in plasma and lung increased very little when the MMI-treated mother was infused with T4, but in the brain T3 reached concentrations comparable to those in normal fetuses. Results not only show transfer of T4 from the mother to the fetus near term, at least when the fetal thyroid is impaired, but also suggest that it might mitigate, or avoid, the adverse effects of such failure on the developing brain. PMID- 3345726 TI - Progesterone receptor regulation in T47D human breast cancer cells: analysis by density labeling of progesterone receptor synthesis and degradation and their modulation by progestin. AB - We have examined the effect of progestin on the regulation of cellular progesterone receptor (PR) levels and have used dense amino acid-density shift experiments to determine the mechanism by which progestin markedly decreases PR. We have utilized T47D human breast cancer cells which contain high levels of PR and are progestin responsive. When these cells are exposed to the progestin R5020, there is a time- and concentration-dependent decrease in PR levels. Experiments with different concentrations of R5020 reveal that the rate and extent of PR decrease reflect the time course of receptor occupancy and the fractional saturation of receptor. With a high concentration of ligand (20 nM) that labels all receptors rapidly, reductions in PR levels (processing) occur immediately and proceed rapidly to levels that are 15-20% of the initial; at lower concentrations (5 nM), where it takes several hours to achieve full saturation of receptors, there is a delay before the maximal rate of processing develops and then continues to achieve final receptor levels that are 15-20% of the initial; with a low concentration of ligand (0.5 nM), binding is even slower and never reaches full receptor saturation, with the consequence that processing is not only delayed but also less complete. Immunochemical detection of PR with a monoclonal antibody (B39) reveals a good correspondence between the loss of immunoreactive and hormone binding PR, and analysis of the A (Mr 85,000) and B (Mr 115,000) receptor forms on Western blots demonstrates that both A and B receptor forms are reduced after exposure to R5020. Density labeling of PR by biosynthetic incorporation of 2H, 13C, 15N (dense) amino acids reveals that PR turns over with a half-life of 21 h in control cells. In cells exposed to 20 nM R5020, PR levels decline and receptor half-life is reduced to 6 h. In addition, there is also a time-dependent decrease in the rate constant of PR synthesis, k8, which decreases to less than 10% of its initial value after 24 h of R5020 exposure. Thus, the R5020-evoked reduction in PR levels in this progestin sensitive cell line is due both to a marked increase in the rate of receptor degradation as well as a dramatic decrease in the rate of receptor synthesis. PMID- 3345728 TI - Progesterone and antiprogesterone (RU 38486) modulation of estrogen-inducible glycoprotein (USP-1) synthesis and secretion in rat uterine epithelial cells. AB - Previous study in this laboratory revealed that estrogen stimulates synthesis and secretion of 97K glycoprotein [uterine secretory protein-1 (USP-1)] in rat uterine epithelial cells. In the present communication, the effects of progesterone and antiprogesterone (RU 38486) on estrogen-stimulated USP-1 biosynthesis were investigated. Ovariectomized rats were treated with estrogen for 4 days to induce USP-1 synthesis and secretion. Then, progesterone and RU 38486 were injected sc. After 6 and 12 h of treatment, uterine luminal fluid proteins were labeled for 6 h by direct administration of [35S]methionine into uterine lumen. By radioimmune precipitation assay using specific antibody against USP-1, it was shown that progesterone can reduce the USP-1 synthesis and secretion, which were prestimulated by estrogen. This antagonistic effect of progesterone on estrogen-induced USP-1 biosynthesis was also evident by the decreased staining intensity of USP-1 in uterine epithelial cells, as revealed by the immunohistochemical method. Although RU 38486 itself did not manifest any effect on estrogen-stimulated USP-1 biosynthesis, it completely inhibited the progesterone-induced decrease in synthesis and secretion. This system is believed to provide a useful model to analyze the progesterone and antiprogesterone actions on rat uterine epithelial cells. PMID- 3345727 TI - Gastrin-releasing peptide gene expression in developing, hyperplastic, and neoplastic human thyroid C-cells. AB - Gastrin-releasing peptide (GRP), the mammalian homolog of bombesin, is often studied as a prototypic neuroregulatory hormone and growth factor, but its own regulation and physiological roles remain to be fully defined. We now demonstrate that the GRP gene is expressed in human thyroidal calcitonin (CT)-containing neuroendocrine cells (C-cells) in an ontogenic pattern similar to its expression in pulmonary neuroendocrine cells and is also expressed at high levels in C-cell hyperplasias and neoplasias (medullary carcinomas of the thyroid). Mean GRP-like immunoreactivity is 20 times higher in 3-week-old to 5-month-old infants than in normal adults, with six of seven infants having GRP levels 6- to 67-fold higher than those in normal adults, the highest levels occurring at 2-2.5 months. CT levels are about 100 times greater than GRP levels at all time intervals, with levels of GRP and CT being linearly correlated (r = 0.98). By RNA blot analysis, GRP mRNAs are increased in neonatal thyroids compared to adult thyroids. In situ hybridization and immunoperoxidase analyses localize GRP mRNAs and peptide to a majority of C-cells in fetuses and neonates, but to only 5-18% of C-cells in normal adults. The majority of developing C-cells have a dendritic morphology, suggesting a paracrine role, although this morphology is not observed in adult C cells. In addition, for unknown reasons, an increased percentage of C-cells positive for GRP occurs in normal thyroid adjacent to GRP-negative follicular adenomas and papillary carcinomas, an association that we term perineoplastic. We hypothesize that GRP gene expression may play a role in both normal and neoplastic growth processes. PMID- 3345729 TI - Correlation of spatial differences in concentrations of prolactin and growth hormone cells with vascular pattern in the female mouse adenohypophysis. AB - Adult female mice of the DDY/S strain were used to study the distribution of PRL or GH cells and the vasculature of the anterior pituitary lobe. Electron microscopy was used to quantify PRL or GH cells in horizontal sections. Most parenchymal cells were either PRL or GH cells, and both types of cells were present in all regions. The densities of PRL cells in the rostral and caudal areas were significantly greater than that of GH cells. The density of GH cells was greater in the anterolateral wings. Thus, the spatial differences in concentrations of PRL and GH cells were reversed. The vasculature was studied with scanning electron microscopy of vascular casts and with stereoscopy of pituitary glands injected with India ink. The adenohypophysis was supplied by long and short portal vessels. The long portal vessels originated from the primary capillary plexus on the median eminence and the upper portion of the pituitary stalk, and they supplied rostral regions of the adenohypophysis. Most of the short portal vessels connected caudal areas of the anterior lobe with the posterior lobe, crossing the surface of the intermediate lobe. The blood in the short portal vessels may flow from the posterior lobe toward the anterior lobe. Thus, within the rostral and caudal areas, which are supplied by long and short portal vessels, respectively, PRL cells predominated; the anterolateral wings where GH cells predominated were far from these regions. These data suggest that the anatomical pattern of the blood supply may account in part for the spatial distribution of PRL and GH cells. PMID- 3345730 TI - Effects of 17 beta-estradiol on high energy phosphate concentrations and the flux catalyzed by creatine kinase in immature rat uteri: 31P nuclear magnetic resonance studies. AB - 31P nuclear magnetic resonance (NMR) was used to study the effects of 17 beta estradiol on the content of phosphates and on the flux catalyzed by creatine kinase in immature rat uteri. Perifusion with oxygenated medium at 36 C maintained the uteri in a viable state for at least 10 h in vitro during 31P NMR measurements. In vitro administration of 17 beta-estradiol to the perifused uteri induced changes in the concentration of the high energy phosphates similar to those found after in vivo stimulation: a rapid fall in the concentrations of ATP, phospho-creatine, and the phosphomonoesters during the first 2 h, followed by a slower return to initial concentrations by approximately 6 h. Analysis of the time course of this modulation indicated that after estrogen stimulation, the energy utilization rate was about twice the production rate. The flux through the creatine kinase (CK) reaction was measured independently using 31P magnetization transfer techniques; it was found to increase in uteri 24 h after estradiol injection by the same extent (65%) as the specific activity of CK measured by a spectrophotometric assay. The congruence between the results of these two techniques (in the absence of increased substrate concentrations) provides evidence that the early stimulation of brain-type CK synthesis by estrogen results in a net increase in the concentration of this enzyme. PMID- 3345731 TI - Inhibin: definition and nomenclature, including related substances. PMID- 3345733 TI - Study of the fucosyltransferase system in intestinal microsomes. AB - Fucosyltransferase activity of rat small intestine microsomes is solubilized by 0.5% Triton X-100. The solubilized activity can be purified up to 8,300-fold using DEAE-cellulose and affinity chromatography on GDP-Sepharose. At this step, chromatography on Sephadex G15 separates different specificities: N acetylglucosaminide-alpha-(1,3)-fucosyltransferase acting on asialoserotransferrin, and galactoside-alpha-(1,2)-fucosyltransferase acting on O glycans of asialofetuin. The use of small saccharidic acceptors also indicates the presence of a N-acetylglucosaminide-alpha-(1,4)-fucosyltransferase and of a very weak glucose-alpha-(1,3)-fucosyltransferase activity. These activities are tightly bound to concanavalin A-Sepharose, suggesting that they are supported by N-glycosylproteins. PMID- 3345732 TI - Increase of enzyme activities following the in vitro peroxidation of normal human red blood cells. AB - Red blood cells (RBCs) from 15 normal human blood samples were incubated with different concentrations of hydrogen peroxide in sodium azide, and the effects of the peroxidation on several glycolytic and nucleotidic enzyme activities were investigated. The release of malonyl dialdehyde (MDA) and methemoglobin formation were used as indicators of RBC peroxidation. The increase of H2O2, final concentration from 0.1 to 5 mmol/l, resulted in a progressive rise of almost all glycolytic enzyme activities, especially those of aldolase (200% of normal at 1 mmol/l), phosphoglycerate kinase (140%), phosphoglycerate mutase (136%), pyruvate kinase (130%) and glutathione peroxidase (130%), and in a decrease of glucose-6 phosphate dehydrogenase (68%) and pyrimidine-5-nucleotidase (23%). The addition of beta-mercaptoethanol to the incubation medium abolished only the effect of 1 mmol/l H2O2 on glucose-6-phosphate dehydrogenase. PMID- 3345734 TI - Effect of some thiol reagents on erythrocyte adenosine deaminase (ADA) activity. AB - The effect of three thiol reagents on erythrocyte adenosine deaminase (ADA) activity has been studied. Oxidized glutathione and iodoacetate do not alter ADA activity, while the treatment with p-chloromercuribenzoate at similar concentrations results in a reduction of enzymatic activity which is statistically significant only for ADA 1, but not ADA 2-1 phenotype haemolysates. PMID- 3345735 TI - Pyruvate carboxylase activity in chorionic villi: possibility of application to prenatal diagnosis. AB - Pyruvate carboxylase (PC) activity was assayed in 27 chorionic villi samples (CVS) obtained at 9-12 weeks of gestation. The kinetic properties of the CVS enzyme were similar to those of liver PC; more than 75% of PC activity was recovered in the mitochondrial fraction of CVS. Apparent Km for pyruvate, ATP, acetyl CoA and HCO3- in the presence of saturation concentrations of the other reactants, were 0.3, 0.44, 0.015 and 6.0 mmol/l, respectively. The optimum pH was 7.5-8.0. The activity of PC in CVS was 3.2 +/- 0.3 nmol/min/mg protein, which is severalfold higher than that of amniotic fluid fibroblasts. PMID- 3345736 TI - Metabolism of 2-acetylaminofluorene in the Chinese hamster ovary cell mutation assay. AB - Chinese hamster ovary (CHO) cells were exposed to 2-acetylaminofluorene (2-AAF) and 2-aminofluorene (2-AF), and several of their N-oxidized metabolites in order to study the mechanisms by which arylamides and arylamines produce mutations in mammalian cells. The number of mutations induced at the hypoxanthine-guanine phosphoribosyl transferase locus by each compound (mutants/10(6) CHO cells/nmol compound/ml) was estimated to be: N-acetoxy-2-AAF, 310; N-hydroxy-2-AF, 3; N hydroxy-2-AAF (with and without hepatic S9 activation), 0.7; 2-AAF (with S9), 0.1; and 2-AF (with S9), 0.09. With each compound, DNA adducts were also identified and quantified, and in all cases the major adduct was N-(deoxyguanosin 8-yl)-2-AF. 2-AAF and N-hydroxy-2-AAF also formed minor amounts of N (deoxyguanosin-8-yl)-2-AAF and 3-(deoxyguanosin-N2-yl)-2-AAF. The relationship between mutation induction and adduct formation for each of the derivatives was similar to that previously reported for N-hydroxy-2-AF. Inclusion of the deacetylase inhibitor, paraoxon, reduced the mutagenicity of 2-AAF, N-hydroxy-2 AAF and N-acetoxy-2-AAF, and the DNA adducts produced by N-acetoxy-2-AAF to background levels. Acetyl coenzyme A increased the mutations and CHO cytosol mediated DNA binding of N-hydroxy-2-AAF, but did not substantially increase these responses from N-hydroxy-2-AF. N-Hydroxy-2-AAF was not detectably metabolized by CHO cells. Taken together, these data indicate that CHO cells metabolized N acetoxy-2-AAF to a reactive derivative by N-deacetylation to N-acetoxy-2-AF, while N-hydroxy-2-AF reacted directly with DNA. The major pathway of N-hydroxy-2 AAF activation appeared to be an initial O-acetylation to N-acetoxy-2-AAF and this occurred to only a limited extent in the CHO cells. N-Hydroxy-2-AAF also seemed to form an additional unknown ester intermediate that gave rise to acetylated DNA adducts. The initial step in the activation of 2-AAF and 2-AF was an N-oxidation to N-hydroxy-2-AAF and N-hydroxy-2-AF, respectively. The limited O acetylase activity in CHO cells appeared to contribute to the low sensitivity of these cells toward mutation induction by arylamines and arylamides. PMID- 3345737 TI - Occurrence in vivo of sister chromatid exchanges at the same locus in successive cell divisions caused by nonrepairable lesions induced by gamma rays. AB - The capacity of lesions induced by gamma radiation to produce sister chromatid exchanges (SCE) in successive divisions in mouse bone marrow cells in vivo was evaluated using a protocol for the three-way differentiation of sister chromatids. Evidence was obtained that exposure to gamma radiation induces DNA lesions that result in the formation of SCE at the same locus in two successive cell divisions. The relevance of this observation with respect to DNA repair and mutagenesis is discussed. PMID- 3345739 TI - Clastogenicity of tritiated thymidine to the mouse bone marrow. AB - Tritiated thymidine (3HTdR; 120 microCi/mouse) increases the incidence of micronucleated polychromatic erythrocytes (MPE) in bone marrow PE of both B6CF1 and CBA male mice. This effect observed in vivo reflects, the clastogenicity reported by other investigators for 3HTdR in vitro. Thymidine itself was concluded to be inactive in the assay at a dose-level 100 times greater than that required to show activity for 3HTdR. These observations are of relevance to those employing 3HTdR to monitor the mitogenic activity and the genotoxicity of chemicals. PMID- 3345738 TI - Detection of TEM-induced reciprocal translocations in F1 sons of CD-1 male mice: comparison of sequential fertility evaluation and cytogenetic analysis. AB - To determine the positive and negative classification error rates associated with the HTA in our laboratory, F1 sons of TEM-exposed CD-1 male mice were evaluated by the sequential fertility method with subsequent cytogenetic analysis. Males who sired three litters of size 10 or less when mated to primiparous females from either the B6C3F1 or the BCF1 strain were classified as partial steriles. When meiotic chromosome analyses revealed the presence of at least two cells containing multivalent figures, males were classified as translocation heterozygotes. When the fertility evaluation and the cytogenetic analysis were compared, normal fertility was observed on 5 of 83 (6.02%) translocation-bearing F1 males mated to B6C3F1 tester females and on 3 of 83 (3.61%) F1 males mated to BCF1 tester females. Thus, the false-negative error rates were 6.02% and 3.61% with these two tester strains. Multivalent figures were not observed in the meiotic chromosomes of 410 F1 males. Of these, 12 (2.93%) had reduced fertility when mated to the B6C3F1 tester strain as did 7 (1.71%) mated to the BCF1 strain. Thus, the false-positive error rates with these two tester strains were 2.93% for the B6C3F1 strain and 1.71% for the BCF1 strain. Our results indicate that non zero error rates, both false-positive and false-negative, are associated with the sequential mating method HTA. In addition, the magnitude of these error rates was influenced not only by the tester female strain but also by the genotype of the F1 male. PMID- 3345740 TI - Guidelines on the use of mutagenicity tests in the toxicological evaluation of chemicals. A report of the DNH&W/DOE Envionmental Contaminants Advisory Committee on Mutagenesis. PMID- 3345741 TI - The Na+/K+/Cl- cotransport in C6 glioma cells. Properties and role in volume regulation. AB - The role of the Na+/K+/Cl- cotransporter in the regulation of the volume of C6 astrocytoma cells was analyzed using isotopic fluxes and cell cytometry measurements of the cell volume. The system was inhibited by 'loop diuretics' with the following order of potency: benzmetanide greater than bumetanide greater than piretanide greater than furosemide. Under physiological conditions of osmolarity of the incubation media, equal rates of bumetanide-sensitive inward and outward K+ fluxes were observed. Blockade of the Na+/K+/Cl- cotransporter with bumetanide did not lead to a modification in the mean cell volume. When C6 cells were incubated in an hyperosmotic solution, a cell shrinkage was observed. It was accompanied by a twofold increase in the activity of the Na+/K+/Cl- cotransport, which then catalyzed the net influx of K+. In spite of this increased activity, no cell swelling could be measured. Incubation of the cells in an iso-osmotic medium deprived of either Na+, K+ or Cl- also produced cell shrinkage. Large activations (up to tenfold) of the Na+/K+/Cl- cotransport together with a cell swelling back to the normal volume were observed upon returning ion-deprived C6 cells to a physiological solution. This cell swelling was completely prevented in the presence of bumetanide. It is concluded that the Na+/K+/Cl- cotransport system is one of the transport systems involved in volume regulation of glial cells. The system can either be physiologically quiescent or active depending on the conditions used. A distinct volume regulating mechanism is the Na+/H+ exchange system. PMID- 3345742 TI - Human heme oxygenase cDNA and induction of its mRNA by hemin. AB - Hemin treatment increased both activity and mRNA level of heme oxygenase in human macrophages. Using poly(A)-rich RNA prepared from human macrophages treated with hemin, we have constructed a cDNA library in the Okayama-Berg vector. The human heme oxygenase cDNA was isolated by screening this library with a rat cDNA and was subjected to nucleotide sequence analysis. The deduced human heme oxygenase is composed of 288 amino acids with a molecular mass of 32,800 Da. The homology in amino acid sequences between rat and human heme oxygenase is 80%. Like rat heme oxygenase, human enzyme has a putative membrane segment at its carboxyl terminus, which is probably essential for the insertion of heme oxygenase into endoplasmic reticulum. Both rat and human heme oxygenase have no cysteine residues. Recently we have shown that rat heme oxygenase is a heat-shock protein [J. Biol. Chem. 262, 12889-12892 (1987)], and therefore we examined the effects of heat treatment on the induction of heme oxygenase in human macrophages and glioma cells. In contrast to hemin treatment, heat treatment had no apparent effects in either human cell line on the activity of heme oxygenase and its mRNA levels. These results suggest that human heme oxygenase may not be a heat-shock protein. PMID- 3345743 TI - Purification and characterization of five forms of glutathione transferase from human uterus. AB - Five glutathione transferase (GST) forms were purified from human uterus by glutathione-affinity chromatography followed by chromatofocusing, and their structural, kinetic and immunological properties were investigated. Upon SDS/polyacrylamide slab gel electrophoresis all forms resulted composed of two subunits of identical molecular size. GST V (pI 4.5) is a dimer of 23-kDa subunits. GST I (pI 6.8) and GST IV (pI 4.9) are dimers of 24-kDa subunits whereas GST II (pI 6.1) and GST III (pI 5.5) are dimers of 26.5-kDa subunits. GST V accounts for about 85-90% of the activity whereas the other isoenzymes are present in trace quantities. On the basis of the molecular mass of the subunits, amino acid composition, substrate specificities, sensitivities to inhibitors, CD spectra and immunological studies, GST V appeared very similar to transferase pi. Structural and immunological studies provide evidence that GST IV is closely related to the less 'basic' transferase (GST pI 8.5) of human skin. Extensive similarities have been found between GST II and GST III. The comparison includes amino acid compositions, subunits molecular size and immunological properties. The two enzymes, however, are kinetically distinguishable. The data presented also indicate that GST II and GST III are related to transferase mu and to transferase psi of human liver. Even though GST I has a subunit molecular mass identical to GST IV, several lines of evidence, including catalytic and immunological properties, indicate that they are different from each other. GST I seems not to be related to any of known human transferases, suggesting that it may be specific for the uterus. PMID- 3345744 TI - Preferential positioning of nucleosomes on pBR322 as evaluated via Fourier transform of data from electron microscopy. AB - Nucleosome positioning on pBR322 DNA has been evaluated by electron microscopy visualization, after psoralen cross-linking. The distribution function of nucleosomes on pBR322 DNA has been calculated analyzing the data of the electron microscopy via Fourier transform. This function shows definite maxima, which indicate differential interactions of the histone octamer to different DNA sequences. PMID- 3345745 TI - Reversal of snake neurotoxin binding to mammalian acetylcholine receptor by specific antiserum. AB - Snake curaremimetic toxins are known to bind to the nicotinic acetylcholine receptor (AcChoR) [Changeux et al. (1970) Proc. Natl Acad. Sci. USA, 67, 1241 1247], thus blocking neuromuscular transmission, and producing respiratory failure in mammals. In the present paper we show that the toxic effects of Naja nigricollis toxin alpha to mammals can be efficiently reversed by toxin-alpha specific antibodies. In vivo we observed that return to normal breathing in toxin alpha-intoxicated and ventilated rats was 12 times faster after injection of specific antiserum or monoclonal antibody (M-alpha 1) as compared with control animals. Ex vivo we observed that return to normal contraction of a toxin-alpha blocked phrenic nerve-hemidiaphragm preparation was 14 times more rapid after treatment with specific antiserum than after washings. In vitro we observed that antibodies accelerated the reversal of binding of [3H]toxin alpha to AcChoR prepared from rat diaphragm. The observation made in vitro furthermore indicates that antibodies are capable of destabilizing the [3H]toxin-AcChoR complex. A similar destabilization phenomenon occurs also in vivo, as inferred from measurements of receptor occupancy by [3H]toxin alpha in diaphragm of anaesthetized rats in the presence or absence of antibodies. The property of antibodies to reverse neurotoxin binding to AcChoR may be considered as a critical test for evaluation of the quality of a neurotoxin-specific antisera. PMID- 3345747 TI - Structure function studies on the lipoate-acetyltransferase--component-X-core assembly of the ox heart pyruvate dehydrogenase complex. AB - Component X, the recently recognised subunit of mammalian pyruvate dehydrogenase complex, was shown by immune blotting to be present in all of nine tissues dissected from rat. This finding indicated that component X was not an isoenzyme of the lipoate acetyltransferase (E2) associated with one or a limited number of tissues. Native pyruvate dehydrogenase complex was shown to bind IgG raised to isolated component X, indicating that there were at least some regions of the X subunit exposed at the periphery of the complex. Lipoyl groups of ox heart pyruvate dehydrogenase complex were specifically cross-linked by reaction with phenylene-o-bismaleimide in the presence of pyruvate and the subunits contributing to the products of cross-linking were identified by immune blotting. Species with very high Mr containing both E2 and component X, were formed in high yield, as well as apparent E2/E2 and E2/X dimers and trimers and an X/X dimer. These results showed that acetylated lipoyl groups of different E2 and X subunits were able to interact in all possible combinations. The types of cross-linked E2 products formed suggested that two thiols, reactible with phenylene-o bismaleimide, were rapidly generated in the presence of pyruvate. The results were most easily explained by the presence of two acetylatable lipoyl groups on each E2 polypeptide. PMID- 3345746 TI - Mapping of catalytic domains and phosphorylation sites in the multifunctional pyrimidine-biosynthetic protein CAD. AB - We have examined the domain organization, and the locations of the sites phosphorylated by the cyclic-AMP-dependent protein kinase, in the multifunctional polypeptide of the pyrimidine-biosynthetic protein, CAD. Fragments produced after limited proteolysis by elastase or trypsin were separated by SDS/polyacrylamide gel electrophoresis and transferred onto nitrocellulose. The blots were probed with antibodies raised against the core aspartate carbamoyltransferase (ACTase) and dihydroorotase (DHOase) fragments to locate fragments containing these domains, and we also examined the locations of the phosphorylation sites by complete tryptic digestion of blotted, 32P-labelled fragments, followed by analytical isoelectric focussing. Our results are consistent with the domain order glutaminase(GLNase)-carbamoyl-phosphate synthetase-(CPSase)-DHOase-ACTase, as suggested by recently reported homologies between the predicted amino acid sequence for the Drosophila rudimentary gene product, and monofunctional CPSases/ACTases/DHOases. In particular, the finding of a 95-kDa elastase fragment which cross-reacted with both anti-DHOase and anti-ACTase antibodies rules out the previously suggested domain order: DHOase-GLNase-CPSase-ACTase. Phosphorylation by cyclic-AMP-dependent protein kinase accelerates cleavage of native CAD by both elastase and trypsin, and abolishes the protective effect of UTP. Site 1 is located close to the C-terminal end of the 160-kDa GLNase/CPSase region. Comparison with the predicted amino acid sequence of the Drosophila rudimentary gene revealed a strong homology between the tryptic peptide containing site 1 from hamster CAD, and a region at the extreme C-terminal end of the CPSase II domain of the Drosophila enzyme. Alignment of the Drosophila sequence and that of rat liver CPSase I, which is not phosphorylated by cyclic AMP-dependent protein kinase, revealed that this putative site 1 region is missing in CPSase I. Site 2 could not be located with certainty, either from the limited proteolysis data, or from comparison of the sequence around this site and the sequence of the rudimentary gene. There were also one or more previously undetected minor phosphorylation site(s) located in the protease-sensitive hinge region between the DHOase and ACTase domains. PMID- 3345748 TI - Carbamoyl-phosphate synthetase I. Kinetics of binding and dissociation of acetylglutamate and of activation and deactivation. AB - The dissociation of the cofactor, acetylglutamate, from the enzyme-cofactor complex formed by carbamoyl-phosphate synthetase I of rat liver in the presence of ATP, Mg2+, K+ and HCO-3 has been studied by centrifugal gel filtration. The rate of its dissociation (k, 0.13 s-1) is considerably slower than the rate of enzyme turnover (approximately equal to 6 s-1) and it is not increased by ammonia, although ammonia reduces the rate of reassociation of the cofactor. Omission of ATP, Mg2+ or K+ from the column buffer leads to virtually complete dissociation of bound acetylglutamate during passage through the column (0.5-2 min), owing to an increase in dissociation and a decrease in reassociation, but reduction of free Mg2+ alone has the opposite action. Dilution of the enzyme cofactor complex into a large volume of buffer causes a biphasic loss of enzyme activity with a t1/2 of the first phase comparable with that of the dissociation of acetylglutamate. These findings show (a) that acetylglutamate does not dissociate with each turnover of the enzyme; (b) that there are rapid interactions between binding of acetylglutamate and ATPA (ATPA yields Pi in the overall reaction), Mg2+ and K+, suggesting that these ligands bind in close proximity; and (c) that the enzyme transiently retains considerable activity after dissociation of the cofactor. PMID- 3345749 TI - Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 1. Structure of 16 oligosaccharides having the Gal beta(1----3)GalNAc-ol core (type 1) or the Gal beta(1----3)[GlcNAc beta(1----6)]GalNac-ol core (type 2). AB - Carbohydrate chains of respiratory-mucus glycopeptides from a patient (blood group O) suffering from bronchiectasis with a Kartagener's syndrome have been released by alkaline borohydride treatment. Application of high-performance liquid chromatography using subsequently two silica columns, one bonded with aminopropyl groups and the other with octadecyl groups, afforded 39 neutral fractions; 35 oligosaccharide-alditol structures have been characterized by employing 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis. Here, 16 oligosaccharide structures, possessing a core consisting of Gal beta(1--- 3)GalNAc-ol branching through a GlcNAc residue linked beta(1----6) to the GalNAc residue (core type 2 or core type 1, respectively), are described. Ten oligosaccharide-alditols with these types of cores (2, 3, 10a, 14, 7, 11a, 15a, 16a, 12 and 16c) have been identified previously in human bronchial mucins of patients suffering from cystic fibrosis [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.H.G.M., Van Halbeek, H. and Vliegenthart, J.F.G. (1984) Eur. J. Biochem. 143, 227-236]. Of the remaining six compounds, one is a partial structure of oligosaccharides previously described: (Formula: see text). The structures 17a and 20 contain the Y determinant, i.e., Fuc alpha(1----2)Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----). High-resolution 1H-NMR spectroscopy is able to distinguish whether the Y determinant is beta(1----3) or beta(1----6) linked in such oligosaccharide-alditols. PMID- 3345751 TI - Biosynthesis of vitamin B-12 in anaerobic bacteria. Experiments with Eubacterium limosum on the origin of the amide groups of the corrin ring and of N-3 of the 5,6-dimethylbenzimidazole part. AB - The pathway of vitamin B-12 biosynthesis in anaerobic bacteria differs in several respects from the pathway found in aerobic or aerotolerant microorganisms. The aim of this investigation was to elucidate the formation of the 5,6 dimethylbenzimidazole part and the amide groups of vitamin B-12 in anaerobic bacteria. [15N]Ammonium chloride or L-[amido-15N]glutamine or a mixture of [15N]ammonium sulfate and [15N]glycine was added to fermentations with Eubacterium limosum. The vitamin B-12 isolated from these fermentations was methylated and degraded to cobinamide and 1,5,6-trimethylbenzimidazole. The amide groups of cobinamide were hydrolyzed and the amide nitrogen of the side chains a, b, c, d, e and g trapped as benzamide. The 15N incorporation was determined by mass spectroscopy. Thus in the experiment with [15N]ammonium chloride the benzamide and the 1,5,6-trimethylbenzimidazole contained 9.6% 15N, whereas in the experiment with L-[amido-15N]glutamine 37.5% of the molecules were 15N labeled. The 1H-NMR spectrum of 1,5,6-trimethylbenzimidazole revealed that the 15N from the ammonium salts and from glutamine was incorporated into N-3 of the 5,6 dimethylbenzimidazole moiety of vitamin B-12. With a mixture of [15N]ammonium sulfate and [15N]glycine both nitrogens of 5,6-dimethylbenzimidazole became 15N labeled. These experiments demonstrate that in E. limosum the amide nitrogen of glutamine is not only the precursor of the six amide groups of the corrin ring, but also of N-3 of the 5,6-dimethylbenzimidazole moiety of vitamin B-12. PMID- 3345750 TI - Primary structure of neutral oligosaccharides derived from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis, determined by combination of 500-MHz 1H-NMR spectroscopy and quantitative sugar analysis. 2. Structure of 19 oligosaccharides having the GlcNAc beta(1----3)GalNAc-ol core (type 3) or the GlcNAc beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol core (type 4). AB - A pool of neutral carbohydrate chains was prepared from respiratory mucins of a patient suffering from bronchiectasis. Fractionation by HPLC led to 35 smaller size oligosaccharide-alditols; the structure of 16 oligosaccharide-alditols with core type 1 or type 2 has been established (Klein, A., Lamblin, G., Lhermitte, M., Roussel, P., Breg, J., Van Halbeek, H. & Vliegenthart, J.F.G., preceding paper in this journal). In this second part, we identified 19 oligosaccharide alditols possessing core types 3 and 4. Nine of the structures (1, 5, 9, 6, 10b, 13, 19, 15b and 18.1) have been described previously to be present in cystic fibrosis mucins [Lamblin, G., Boersma, A., Lhermitte, M., Roussel, P., Mutsaers, J.G.H. M., Van Halbeek, H. & Vliegenthart, J.F.G. (1984) Eur. J. Biochem. 143, 227-234]. The remaining ten are new structures isolated from bronchial mucins; they are all extensions of the above-mentioned nine oligosaccharides. These compounds are octassaccharide-alditols containing the Y determinant together with the H determinant of either backbone-type 1 or 2, and partial structures thereof: (Formula: see text) and 21b, which is 23c without Fuc alpha(1----3), 18.2, which is 23c without any Fuc in the 6-branch, and 22b, which is 23c without Fuc in the 3-branch. PMID- 3345752 TI - The interaction of alpha-tocopherol and homologues with shorter hydrocarbon chains with phospholipid bilayer dispersions. A fluorescence probe study. AB - The intrinsic fluorescence of tocopherol homologues with hydrocarbon chains ranging from 1 carbon (C1) to 16 carbons (alpha-tocopherol, C16) and their ability to quench the fluorescence of 9-anthroyloxy derivatives of fatty acids with the fluorophore located at different positions in the hydrophobic domain of phospholipid bilayers has been used to model the interaction of tocopherol with lipid bilayer membranes. All the tocopherol homologues used, C1, C6, C11 and alpha-tocopherol, showed a similar fluorescence emission intensity at 325 nm in cyclohexane but were almost completely self-quenched by aggregation in water. Fluorescence was restored when dispersions of dimyristoylglycerophosphocholine were added but the maximum intensity was lower with the longer-chain homologues. Full intensity was observed in all homologues on addition of the detergent Triton X-100. Studies using 9-anthracenecarboxylic acid and 9-anthracenecarboxymethyl ester, 6-(9-anthroyloxy)stearic acid and 16-(9-anthroyloxy)palmitelaidic acid showed that the tocopherol homologues partitioned into the hydrophobic domain of phospholipid dispersions composed of dimyristoylglycerophosphocholine at 40 degrees C and dioleoylglycerophosphocholine at 40 degrees C. The 9-anthroyloxy fatty acids and 1,6-diphenyl-1,3,5-hexatriene were quenched by all the homologues and Stern-Volmer plots of the concentration dependence of the quenching indicated that this was predominantly via dynamic processes. No fluorescence energy transfer was observed between diphenylhexatriene and tocopherols but efficient transfer was recorded to the 9-anthroyloxy fatty acid probes. The results are consistent with a model in which the chromanol nucleus of tocopherol is oriented towards the lipid-water interface of the phospholipid bilayer. As the phytol chain length increases there is an increasing tendency for the chromanol nucleus to reside in the hydrophobic interior of the structure. alpha-Tocopherol appears to form clusters within the phospholipid dispersion which are not fluorescent and do not quench the fluorescence of the different fluorescent probes nor transfer fluorescence energy to them. It is suggested that the monomeric form is responsible for the vitamin effects of tocopherol and the aggregated form acts as a reservoir that does not markedly perturb bilayer stability. PMID- 3345754 TI - Mossbauer studies on the metal-thiolate cluster formation in Fe(II) metallothionein. AB - The stepwise 57Fe(II)-thiolate cluster formation in rabbit liver metallothionein 2 (MT) has been followed at pH 8.5 using Mossbauer spectroscopy. The zero-field spectra recorded at 4.2 K exhibit at all stages of filling one virtually identical single quadrupole splitting delta EQ and isomer shift delta as found for reduced rubredoxin (Rdred) or the model compound [Fe(II)(SPh)4]2-, thus indicating an Fe(II)-tetrathiolate coordination. A similar conclusion was reached also in previous electronic absorption studies [M. Good and M. Vasak (1986) Biochemistry 25,8353--8356]. The Mossbauer spectra obtained in the presence of a magnetic field were analyzed on the basis of a spin-Hamiltonian formalism resulting in Mossbauer parameters similar to those for Rdred and the inorganic model compound [Fe(II)(SPh)4]2-. The identity of the Mossbauer parameters of partially and fully metal-occupied MT suggests that a comparable distortion of the metal binding sites must exist. Simulation of the spectra revealed that the Fe(II) ions in the partially metal-occupied 57Fe(II)4-MT form appear to be magnetically isolated, whereas in the fully metal-saturated 57Fe(II)7-MT form a ratio of 3:4 of paramagnetic to diamagnetic subspectra was obtained. The latter result suggests the existence of three isolated metal binding sites and a metal thiolate cluster containing four metal ions. In the light of structure determinations of MT containing Zn(II) and/or Cd(II) [W. Braun et al. (1986) J. Mol. Biol. 187, 125-129, and W. F. Furrey et al. (1986) Science (Wash. DC) 231, 704-710], which revealed two metal-thiolate clusters containing three and four metal ions, respectively, and involving all 20 cysteine residues in metal binding, the appearance of Mossbauer parameters characteristic of three isolated Fe(II) sites in 57Fe(II)7-MT is peculiar and deserves further studies. It is concluded, moreover, that the four-metal cluster is diamagnetic with the four Fe(II) ions being antiferromagnetically coupled. The appearance of magnetic coupling above four Fe(II) equivalents bound to apoMT indicates that the cluster formation occurs in a two-step process. PMID- 3345753 TI - Comparative study of the lateral motion of extrinsic probes and anthracene labelled constitutive phospholipids in the plasma membrane of Chinese hamster ovary cells. AB - 9-(2-Anthryl)-nonanoic acid is a new photoactivatable fluorescent probe which has been designed for the study of the lateral diffusion and distribution of lipids in biological membranes by means of the anthracene photodimerization reaction. This anthracene fatty acid can be incorporated metabolically into the glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol) of Chinese hamster ovary (CHO) cells in culture. The diffusion coefficient of intrinsic lipids in the plasma membrane of these eukaryotic cells can thus be measured using the fluorescence recovery after a photobleaching technique, since illumination of the fluorescent anthracene groups yields non-fluorescent photodimers. For the sake of comparison, the extrinsic lipophilic probes 5-(N-hexadecanoyl)-aminofluorescein, 12-(9 anthroyloxy)-stearic acid, 9-(2-anthryl)-nonanoic acid and a synthetic anthracene phosphatidylcholine were also used to label the plasma membrane of CHO cells. The diffusion coefficients for the extrinsic and intrinsic probes ranged over 1 - 2 x 10(-9) cm2/s. Small but significant differences were observed between the various probes reflecting differences they exhibit in size and polarity. All the extrinsic probes were free to diffuse, with a mobile fraction close to 100%. In contrast, a fractional recovery of only 75% was observed for the intrinsic anthracene-labelled phospholipids, suggesting that the anthracene fatty acid was metabolically incorporated into membrane lipid regions which were inaccessible to the extrinsic probes. PMID- 3345755 TI - The reconstitution of a hybrid histone octamer containing avian 110Cys-des-thio histone H3 and sea-urchin 73Cys-histone H4. AB - A hybrid histone octamer was reconstituted from erythrocyte H2A and H2B, avian [110 Cys-des-thio]histone H3 and the sea-urchin sperm [73Cys]H4 variant. [110Cys Des-thio]histone H3 was prepared by reaction of natural H3 with Raney nickel. The ability of the hybrid octamer to crystallize to the same form as the natural octamer demonstrated that the chemical modification of cysteine to alanine in H3 and the mutation from threonine to cysteine in sperm H4 do not alter histone histone interactions in the octamer. Since the sulfhydryl groups of both H4 molecules are fully accessible to 5,5'-dithiobis(2-nitrobenzoate) these residues provide suitable sites for the introduction of a single cysteine-specific label per H4 molecule in the octamer. PMID- 3345756 TI - 1H nuclear-magnetic-resonance studies of the three-dimensional structure of the cardiotoxin CTXIIb from Naja mossambica mossambica in aqueous solution and comparison with the crystal structures of homologous toxins. AB - Using the previously reported sequence-specific 1H-NMR assignments, structural constraints for the cardiotoxin CTXIIb from Naja mossambica mossambica were collected. These include distance constraints from nuclear Overhauser enhancement measurements both in the laboratory and in the rotating frame, dihedral angle constraints derived from spin-spin coupling constants, and constraints from hydrogen bonds and disulfide bridges. Structure calculations with the distance geometry program DISMAN confirmed the presence of the previously identified antiparallel beta-sheets formed by residues 1-5 and 10-14, and by 20-27, 35-39 and 49-55, and established the nature of the connections between the individual beta-strands. These include a right-handed crossover between the two peripheral strands in the triple-stranded beta-sheet, and a type I tight turn immediately preceding the beta-strand 49-55. The spatial arrangement of the polypeptide backbone in the solution structure of CTXIIb is closely similar to that in the crystal structure of the homologous cardiotoxin VII4 from the same species. In an Appendix the origin of the large pH dependence of two amide proton chemical shifts in CTXIIb is explained. PMID- 3345757 TI - Release of acetylhydrolase from platelets on aggregation with platelet-activating factor. AB - Acetylhydrolase, the enzyme which inactivates platelet-activating factor (PAF, 1 O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine), was selectively released from bovine platelets by aggregation with physiological concentrations (0.1-10 nM) of PAF with no cell lysis. The release of the acetylhydrolase paralleled that of serotonin. The acetylhydrolase released was active over a broad pH range (pH 5.4 8.6) and was not affected by Ca2+ (1-4 mM) or EDTA (1-8 mM). The Km value of the enzyme was 4.6 microM. Net specific acetylhydrolase activity recovered in the 130,000 x g supernatant after stimulation with PAF could be determined in the presence of EDTA without the activity of Ca2+-dependent phospholipase A2 which was also released from the cells at the same concentration of PAF. The acetylhydrolase was inhibited competitively by specific PAF antagonists, rac-3-(N n-octadecylcarbamoyloxy)-2-methyoxypropyl-2-thiazolioe thyl phosphate (CV-3988) and (2RS)-1-O-hexadecyl-2-O-ethyl-3-O-(7-thiazolinoheptyl)-glycerol methanesulfonate (ONO-6040). Their Ki values for the enzyme were 1.17 microM and 0.84 microM, respectively. The release of the enzyme could also be detected when the platelets were aggregated with ADP (2.3 microM) or thrombin (0.5 unit). These results suggest that the enzyme released from the aggregated platelets to the blood plasma may also have a physiological function cooperating with the plasma acetylhydrolase. PMID- 3345758 TI - Characterization of cDNA clones for human glycophorin A. Use for gene localization and for analysis of normal of glycophorin-A-deficient (Finnish type) genomic DNA. AB - Glycophorin A is the major membrane sialoglycoprotein of human erythrocytes and represents a typical example of a transmembrane glycoprotein. The functional role of this cell-surface component is not known but it represents a receptor for viruses, bacteria and parasites like Plasmodium falciparum. 1. Two cDNA clones encoding glycophorin A have been characterized from human fetal cDNA libraries. The longer cDNA extended from the coding region of glycophorin A (residues 4-131) to the 3' untranslated region which included two polyadenylation signals and a poly(A) tail. 2. The structural gene for glycophorin A is located on chromosome 4, q28-q31 as shown by in situ hybridization, thus confirming the previous localization by genetic linkage analysis. 3. Three distinct mRNA species (1.0 kb, 1.7 kb and 2.2 kb) have been identified in erythroid spleen. Northern blot analyses with a probe directed against the 3' untranslated region of the mRNAs indicated that all these species share a homologous 3' non-coding region and that the first polyadenylation signal downstream the stop codon is not used. 4. Preliminary studies by Southern blot analysis of the genomic DNA from normal En(a+) and rare En(a-) donors suggest that the glycophorin A gene has a complex organization and is largely deleted in donors of the En(a-) phenotype (Finnish type) who lack glycophorin A on their red cells. PMID- 3345759 TI - Interaction of a spin-labelled cholesterol derivative with the cytochrome P 450scc active site. AB - The cholesterol analogue 25-doxyl-27-nor-cholesterol (CNO), was found to be a substrate for cytochrome P-450scc. Upon incubation with the cytochrome P-450scc electron transfer system, CNO is transformed to pregnenolone (Km = 33 microM, Vmax = 0.32 min-1). The pregnenolone formation from endogenous cholesterol is strongly inhibited by CNO (50% at 5 microM). It binds tightly to cytochrome P 450scc as evidenced by a reversed type I spectral absorbance change (Kd = 5.9 microM) which is paralleled by a greater hyperfine splitting of the room temperature CNO ESR spectrum due to an enhanced probe immobilization (Kd = 1.9 microM). This finding is in accord with a rotational correlation time of about 10(-7) s, which is close to the tumbling rate of the protein. At 110 K the CNO bound cytochrome P-450scc displays the ESR g-values gx = 2.404/2.456, gy = 2.245 and gz = 1.916; these are different from those of cholesterol-liganded cytochrome P-450scc and may thus serve as a marker for cytochrome P-450scc. Our data indicate that the stereospecificity of the cytochrome P-450scc side-chain cleaving activity is not dependent on the nature of the cholesterol side-chain termination (C25 to C27). The substrate binding site is however rather sensitive to a modification of the side chain. The doxyl ring confers a stronger affinity of the substrate to the enzyme. Upon binding it becomes embedded in the protein matrix, and we estimate that its final position is 0.6-1.0 nm from the heme moiety. PMID- 3345760 TI - Human basement membrane collagen (type IV). The amino acid sequence of the alpha 2(IV) chain and its comparison with the alpha 1(IV) chain reveals deletions in the alpha 1(IV) chain. AB - The cDNA and protein sequences of the N-terminal 60% of the alpha 2(IV) chain of human basement membrane collagen have been determined. By repeated primer extension with synthetic oligodeoxynucleotides and mRNA from either HT1080 cells or human placenta overlapping clones were obtained which cover 3414 bp. The derived protein sequence allows for the first time a comparison and alignment of both alpha chains of type IV collagen from the N terminus. This alignment reveals an additional 43 amino acid residues in the alpha 2(IV) chain as compared to the alpha 1(IV) chain. 21 of these additional residues form a disulfide-bridged loop within the triple helix which is unique among all known collagens. PMID- 3345761 TI - The rat vitamin-D-dependent calcium-binding protein (9-kDa CaBP) gene. Complete nucleotide sequence and structural organization. AB - The structural organization of the entire rat vitamin-D-dependent calcium-binding protein (9-kDa CaBP) gene was determined by analysis of overlapping genomic clones isolated from a rat genomic library using the rat 9-kDa CaBP cDNA [Desplan C., Heidmann O., Lillie J., Auffray C. and Thomasset M. (1983) J. Biol. Chem. 258, 13502-13505]. These clones together span 30 kbp of rat genomic DNA, with the rat 9-kDa CaBP gene lying in the middle. The 9-kDa CaBP gene is 2.5 kbp long and contains three exons interrupted by two introns. The first exon contains almost the entire 5' untranslated region. The second exon codes for the calcium-binding site I, the third exon codes for site II and the 3' untranslated region. Therefore each of the calcium-binding domains is encoded by single, separate exons. The transcription initiation site was identified by S1 nuclease mapping and primer extension. A consensus sequence TATAAA is localized 31 bp upstream from the cap site and the 'CCAAT-box' lies upstream from the transcription start. Single (AC)25 and (AG)23 repeats are present in the second intron together with an Alu-like sequence. Repetitive elements are present 5 kbp upstream from the cap site and in the 3' flanking region. Comparison of the known rat CaBP sequences (9 kDa CaBP, 28-kDa CaBP, S100 protein) shows that the 9-kDa CaBP is more closely related to the S100 protein than to the 28-kDa CaBP. There is no evidence to indicate that 9-kDa CaBP has arisen from the 28-kDa CaBP. PMID- 3345762 TI - Expression of opioid genes in bovine seminal vesicles. AB - In seminal vesicles, the organ producing most of seminal plasma in the bovine species, the pro-opiomelanocortin and the proenkephalin genes are transcribed and translated, and their translation products processed into opioid peptides, which are secreted into the seminal plasma. By using a micro-organ preparation of seminal vesicles we found that, after 20 h of incubation with labelled methionine, a multiplicity of opioids was produced. Among these, [Met]enkephalin and beta-endorphin were positively identified, whereas in the newly formed secretion only [Met]enkephalin was detected. This may be correlated to the finding that the concentration of beta-endorphin in an extract of seminal plasma was one order of magnitude lower than that of [Leu]enkephalin and [Met]enkephalin. These findings expand the picture of the presence of opioid peptides in the male reproductive tract, indicating that they should have a role(s) in the physiology of reproduction, not only in the hypothalamus-pituitary gonadal axis, determining the reproductive potential, but also in the so-termed sex accessory glands, determining the actual events leading to reproduction. To our knowledge this is also the first case studied of opioid peptides produced as exocrine hormones. PMID- 3345764 TI - Isocitrate lyase from Pinus pinea. Characterization of its true substrate and the action of magnesium ions. AB - We found that the Mg-isocitrate complex is the true substrate for pine isocitrate lyase and that magnesium acts as a non-essential activator. Both the non activated and the activated enzyme forms are catalytically active. Our model is consistent with the presence of two Mg-binding sites with different affinities: an activator site with high affinity in addition to the catalytic site with lower affinity. This may result in a complex, fine regulation of isocitrate lyase activity by magnesium. The affinity of the free enzyme for isocitrate is very low. Moreover, free isocitrate does not bind to the activated enzyme, nor it can yield a catalytically active form by binding to an enzyme species whose catalytic site has already been bound by magnesium. PMID- 3345763 TI - Purification of the LSTRA tyrosine protein kinase (p56lck). AB - p56lck, a p60src related tyrosine protein kinase was recently described in a murine lymphoma cell line (LSTRA), in several human lymphomas and in normal peripheral lymphocytes. We have purified p56lck to homogeneity by electrofocusing followed by two-step SDS/polyacrylamide gel electrophoresis. The pure protein was identical to the p56 characterized in LSTRA cells and used to raise antibodies in rabbits. This simple procedure is applicable for the rapid purification of minor proteins. PMID- 3345765 TI - Exercise-induced intermittent angina and ST-segment elevation in Prinzmetal's angina. AB - A patient with primary angina showed intermittent ST elevation (with and without chest pain), during two exercise tests performed on consecutive days; the same ST changes were also seen during the recovery phase. The electrocardiographic changes recorded in this patient may be considered an example of myocardial response to spasm-related ischemia. PMID- 3345766 TI - Amiodarone during pregnancy. AB - A case study is presented in which amiodarone (A) was given during the whole of pregnancy and during the breast feeding period. An intensive observation of thyroid tests, serum concentrations of A and its metabolite, desethylamiodarone (DEA) was undertaken. The child was observed in the same way from birth until 2 months of age. The milk was analyzed for A and DEA. As reported in other published cases, transplacental passage was found and there was a relatively high concentration of amiodarone in the milk. Our child like the other children was healthy at birth, being euthyroid and with no goiter or corneal deposits. No effect was observed of the medication on growth, thyroid tests or cornea. It is concluded that amiodarone can be given during pregnancy but it is advisable to use as low doses as possible and control the serum concentrations at regular intervals. Breast feeding need not be forbidden. PMID- 3345767 TI - Survival of a patient with an infected right atrial myxoma following surgery. AB - We describe an infected right atrial myxoma in a previously healthy 16-year-old schoolboy. He presented with high temperatures and rigors due to staph aureus septicaemia. The illness responded slowly to antibiotics and he became afebrile. Whilst awaiting surgery the temperature recurred. He underwent removal of the myxoma and is the only reported patient to have survived infection of a right atrial myxoma. PMID- 3345768 TI - ESC and ECCO: adventure or joint venture? PMID- 3345769 TI - Improved diagnostic value of echocardiography in patients with infective endocarditis by transoesophageal approach. A prospective study. AB - In a prospective study, the clinical value of transoesophageal two-dimensional echocardiography (TOE) as compared with transthoracic two-dimensional echocardiography (TTE) was determined in patients with suspected infective endocarditis. Ninety-six patients were studied consecutively with an electronic sector scanner using 2.25 and 3.5 MHz probes for TTE and a 3.5 MHz probe embedded in tip of a flexible 12 mm gastroscope for TOE. Results of surgery and autopsy were available for 20 of the 96 patients with infective endocarditis and echocardiographically demonstrated vegetations and 70 control patients with valvular heart disease without infective endocarditis and no signs of vegetations, who were studied preoperatively with TTE and TOE. For TTE and TOE, the measured sensitivity was 63% and 100%, specificity 98% and 98%, positive predictive accuracy 92% and 95%, and negative predictive accuracy 91% and 100%, respectively. In 39 patients who had positive blood cultures, vegetations were found by TOE in 32 patients (82%), but in only 27 patients (69%) by TTE. Image quality was the main factor contributing to the superiority of TOE over TTE: it was reduced in 11/20 patients (55%) in whom vegetations were not detected by TTE. Another important factor was the size of vegetations. Only 6/24 vegetations (25%) of less than 5 mm but 9/13 vegetations of 6-10 mm, and 14/14 vegetations of greater than 11 mm detected by TOE were also observed with TTE. The clinical importance of detecting vegetations was demonstrated by the rate of embolism. In patients with vegetations embolism was 25% when blood cultures were positive and 21% when they were negative. In patients without echocardiographically detectable vegetations signs of embolism were seen in no patient with positive and 7% of the patients with negative blood cultures. Evidence of vegetations was found on the aortic valve in 14 patients and on the mitral valve in seven patients in whom valvular incompetence was not present, indicating that the valve had not yet been damaged significantly. TOE is superior to TTE in detecting vegetations in suspected infective endocarditis because of better image quality, particularly when vegetations are small. TOE seems to be indicated in patients with suspected endocarditis and reduced image quality or negative TTE results. Early detection of vegetations on valves may help confirm the diagnosis of infective endocarditis at an early stage and hopefully lead to an improved prognosis by reducing delay in instituting appropriate therapy. PMID- 3345770 TI - Observations on the capability of the electrocardiogram to detect left ventricular function in chronic severe aortic regurgitation. AB - Echocardiographic parameters of left ventricular (LV) function were compared with the electrocardiographic findings in 40 patients with chronic severe aortic regurgitation. Total 12-lead QRS amplitude was linearly correlated with LV mass and its 'relative reduction' (less than 250 mm) indicated LV hypertrophy. Patients with an electrocardiographic 'strain' pattern had a marked increase LV stress (573 +/- 68 dyn). The association of high total 12-lead QRS amplitude and 'strain' indicate a moderately depressed ejection fraction (EF = 43 +/- 3). Finally, 'strain' and a 'relative reduction' of total 12-lead QRS amplitude were present in patients with a severe depression of EF and contractility. The predictive value of these electrocardiographic indices was confirmed during a mean follow-up of 49 months. In conclusion, the electrocardiogram remains an excellent, easy tool for anatomical and functional investigation of patients with aortic regurgitation. PMID- 3345771 TI - The future of the European Society of Cardiology. PMID- 3345772 TI - Prevalence of tricuspid and pulmonary regurgitation diagnosed by Doppler in apparently healthy women. Possible influence on their physical performance? AB - Ninety-five apparently healthy, non-athletic women aged 24-65 (mean 44) years were screened by Doppler echocardiography for the presence of tricuspid and pulmonary regurgitation (TR and PR). An Irex Meridian system was used. TR was diagnosed in the presence of a pansystolic regurgitant jet into the right atrium with a maximal velocity of greater than 1.5 m s-1. Regurgitant flow throughout diastole was diagnostic for PR. Right-sided regurgitation was found in 43 women (Group 1), 22 with TR, 12 with PR, and nine with combined TR and PR. The remaining 52 women were studied as a control group (Group 2). Group 1 had a significantly larger heart size on X-ray (P less than 0.025) and left ventricular end systolic diameter assessed from M-mode echocardiography (P less than 0.05) than did Group 2. The possible clinical significance of the valvular regurgitation was assessed by using a standardized symptom-limited exercise test on an ergometer bicycle. In Group 1, the mean cumulative work achieved was 7008 (+/- 1630) kpm, and in Group 2 6363 (+/- 1633) kpm (P less than 0.05). TR and PR occurring in otherwise healthy women does not seem to impair physical exercise performance. PMID- 3345773 TI - Diagnostic value of stress radionuclide angiography in coronary artery disease: a comparison of different interpretation criteria. AB - In order to compare different criteria in the interpretation of stress radionuclide angiography (SRNA) 96 patients with suspected coronary artery disease (CAD) were investigated by both SRNA and coronary arteriography. The result of coronary arteriography was taken as the gold standard for the diagnosis of CAD. Left ventricular ejection fraction (LVEF) was measured at each step of the stress study using the equilibrium radionuclide technique. The diagnostic value of eight interpretation criteria based on the evolution of global LVEF during stress were compared with each other, using the ROC technique. The best diagnostic criterion proved to be the normalized increase of LVEF proposed by Goris. The most commonly used criteria, LVEF increase and LVEF measured at maximal exercise, were not optimal. In the whole population of patients, the best criterion had a sensitivity of 85% for a specificity of 80% and a specificity of 83% for a sensitivity of 80%. In the population, following exclusion of patients with preceding myocardial infarction, the specificity was 74% for a sensitivity of 80% and a sensitivity of 74% for a specificity of 80%. Thus, the choice of interpretation criteria is very important in order to optimize the sensitivity and specificity of this diagnostic test. PMID- 3345774 TI - Dose-effect relationship of adenosine provoked angina pectoris-like pain--a study of the psychophysical power function. AB - In an analysis of the psychophysical power function of chest pain induced by adenosine, this agent was repeatedly given in increasing doses into a peripheral vein to six healthy volunteers (five men) aged 23-44 years. On the first day the maximum tolerable dose was determined. On the second day seven doses of adenosine (20, 30, 40, 50, 60, 80 and 100% of the maximum dose) were given single blind in randomized order followed by another seven doses in reversed order. The heart rate was calculated from electrocardiographic recordings. Chest pain was continuously rated according to the CR-10 scale. Before the adenosine test, the perception of sourness was tested similarly with six concentrations of citric acid (1-100 mM). The psychophysical power functions were similar for the perception of sourness provoked by citric acid and chest pain provoked by adenosine, with exponents of 0.69 +/- 0.21 and 0.60 +/- 0.32, respectively. The two modalities showed the same high goodness of fit to the power function (rxy being 0.965 +/- 0.030 and 0.967 +/- 0.033, respectively). For adenosine the group mean relation was R = 1.66(S-2.36)0.6, rxy = 0.999. No signs of tolerance were observed for the chest pain provoked by adenosine. In conclusion, chest pain provoked by adenosine follows a psychophysical power function as with other sensory modalities. PMID- 3345775 TI - Bidirectional transvenous/subcutaneous defibrillation of ventricular fibrillation in dogs: success rates, energy requirements, currents, voltages and impedance. AB - Four hundred and thirteen defibrillations of alternating current-induced ventricular fibrillation were performed in 10 halothane-anaesthetized dogs (body weight: 24.5-30.5 kg). Success rates, energy demands, currents, peak voltages and impedance were determined. A transvenous catheter electrode system (Medtronic 6880, right ventricular apex and superior vena cava, distance 100 or 150 mm) and subcutaneous patch electrodes (Intec 67 L, 2nd/3rd and/or 3rd/4th left intercostal space) were used for bidirectional defibrillation. Loading voltages ranged from 600 to 850 V. With an electrode distance of 100 mm and a pulse duration of 2 ms separated by 1 ms, success rates were 100%, 40% and 0% for 850.650 and 600 V, respectively. With a 3-ms pulse duration, the corresponding rates were 100%, 60% and 50%. With a 2-ms pulse duration, successful defibrillation was achieved with energies lower than 15 J in 27%, with energies between 15 and 20 J in 77%, and 100% with energies higher than 20 J. Defibrillation currents were 4.4-9.3 A for pulse 1 (superior vena cava/ventricular apex) and 6.3-13.4 A for pulse 2 (patch/ventricular apex), respectively. Effective peak voltages ranged from 510 to 787 V and from 514 to 777V and averaged 89.6% of the loading voltages. Impedance values (peak voltage/current) were 75.5-117.7 (pulse 1) and 51.7-94.9 Ohms (pulse 2). Fifty consecutive defibrillations in one animal resulted in a decrease of impedance (114.6 to 84.9 Ohms, pulse 1:75.4 to 53.0 Ohms, pulse 2). Defibrillation of ventricular fibrillation can be achieved with acceptably low energies using a bidirectional transvenous/subcutaneous system, avoiding thoracotomy and general anaesthesia for implantation of the defibrillation system. PMID- 3345776 TI - Oophorectomy in breast cancer. AB - One of the first series that compares Radical Mastectomy alone and Radical Mastectomy plus OO has been reported by Hors'. The OS was better in the group with castration at the moment of mastectomy (primary). Kennedy, recently mentioned in a review by Juret, obtained an overall survival of 53.8 months in 79 patients with primary OO, and of 47.4 months in 96 patients with secondary OO. As can be seen the percentage is almost the same. In this report the disease-free interval was 40.2 months in the primary and 23.9 months in the secondary OO. Here a significant statistical difference is evident. Now, I would like to point out the significant, figures obtained in our first group (primary castration): scarcely 18% of metastases during the second year and 38.6% during the following eight years. In other words, if we expect recurrence or metastases in the order of 72.7% in patients without systemic treatment, the difference is absolutely significant compared with our first group (fig. 1, 2, 3). Let me say as a conclusion, that at the present time a very old procedure in the treatment of breast cancer already has an important place in its management. Maybe in the near future the approach in surgical procedure to the ovary will be different. We are working on that, in terms to be effective without adding psychological damage to this special group of young women with the dreadful Breast Carcinoma. PMID- 3345777 TI - Effective multimodality treatment of epithelial ovarian tumors. AB - Forty patients with epithelial ovarian tumors underwent cyto-reductive surgery followed by a five drug (Adriamycin, D.D.P., 5FU, M.T.X. and C.T.X.) combination chemo and progestin therapy. They all had an initial complete clinical response and 58% were complete histologic responders. One patient developed reactivated disease six months after a negative second look laparotomy. Two of four fatal outcomes were due to development of mixed mesodermal tumors in patients who originally had serous cystadenocarcinomas. We conclude that this regimen is highly effective, independent of residual tumor size, histologic grade of tumor and prior therapy. Its attendant toxicity is acceptably low. PMID- 3345778 TI - How to coordinate the home care with the hospital care for a better quality of life in cancer patients. AB - The author explain some problems concerning the coordination between home and Hospital care for the cancer patients. The problems are Psychological not only for the patients but also for the family and organizing not only for the family but for the Hospital and the social health service. PMID- 3345780 TI - Valuation of some markers in the malignant neoplastic pathology of the female genital tract. AB - The Authors studied the presence of some markers in different gynaecological tumours, by radioimmunoassay. Beta-HCG, 1-alfa-FP, CA 125, GICA and TPA were assayed in 76 patients. Eight of the patients were affected by CIN III, 38 presented a cervical carcinoma (10 at stage I, 14 at stage II, 10 at stage III, 4 at stage IV); 14 patients had an endometrial adenocarcinoma (3 at stage I, 7 at stage II, 2 at stage III and II at stage IV); 12 cases consisted of an ovarian carcinoma with 2 patients at stage I, 5 at stage II and 5 at stage III; 2 patients had a peritoneal diffusion, whereas two women presented a vulvar carcinoma; the control group was formed by 10 patients with no malignant or benign pathology. The results show that tumoral markers, studied in the blood of patients affected by malignant gynaecological tumours, represent a great advantage in the evaluation of both the response to the therapy and of an eventual remission or tumoral recurrence. PMID- 3345779 TI - Review of ovarian cancer of the University of Athens. AB - One hundred and eight patients with cancer of the ovaries were studied retrospectively for a period of seventeen years. All the patients were managed in the Second Department of Obstetrics and Gynecology of the University of Athens. The symptoms of the patients were: pelvic pain in 43, ascites in 27, metrorrhagia in 23 and weight loss in 12. Fifty six per cent of the patients were between 40 to 60 years old and 63% were menopause. The PAP-smear in 40% was class I or II, in 50% was class III and in 10% was class IV-V. The stage of the disease was: 3 patients stage I, stage II 38, stage III 42 and 25 stage IV. No patient had stage 0. Laparotomy was done in all the patients. Thirty eight patients had Co treatment and 42 patients chemotherapy. The pathology report was: serous cystadeno-Ca in 40, mucinous cystadeno-Ca in 38 of the cases, adenocarcinoma 18 and 12 other types of malignant tumors. The follow up of the patients showed a five years survival rate in 10% for stage I, 25% for stage II, 5% for stage III and none for stage IV. PMID- 3345781 TI - Total LDH and its isoenzymes in gynecological malignancies and other gynecological conditions. AB - Total LDH and its five Isoenzymes have been evaluated in 354 patients from a Gynecological Ward. These patients had uterine fibroids, benign ovarian tumors, tubo-ovarian abscesses (T.O.A.), endometrial cancers, cancers of the cervix and ovarian cancers. 90 patients had no gynecological disease and served as controls. A statistical analysis was performed comparing each group of patients with the control group. A significant elevation in total LDH and Iso-IV and a significant decrease in Iso-I was observed in patients with uterine fibroids. Patients with benign ovarian tumors had a significant elevation of total LDH. Patients with T.O.A., Endometrial cancer, cancer of the cervix and cancer of the ovary had a significant elevations of total LDH and Iso-V and a significant decrease in Iso I. When the group of patients with endometrial cancer, cancer of the cervix and cancer of the ovary were compared with each other, no differences could be found in total LDH and Isoenzyme values. We conclude that total LDH and Isoenzyme serum levels are not useful clinical indicators for the diagnosis and management of gynecological malignancies and particularly of ovarian cancer. PMID- 3345782 TI - Pelvic and para-aortic lymph nodal positivity in the ovarian carcinoma: its prognostic significance. AB - Our study is based on 29 patients with ovarian carcinoma in early stage (IA-IIB) having undergone total abdominal hysterectomy, with bilateral salpingo oophorectomy, omentectomy, appendectomy and pelvic and paraaortic lymphadenectomy selective and bioptic. Out of the 29 patients 11 were classified I stage and 18 II stage. Within 3 years, out of 10 patients with node metastases, 1 is alive and free of disease, 6 deceased from the tumor and 3 are alive with residual tumor at various stages of invasion. Out of the 19 patients without nodes metastases 14 are alive and free of disease, 4 deceased from the tumor and 1 is alive with residual carcinoma. Survival related to histological type shows no statistically significant differences. Grading III has a survival of 27.6%, while the other two grades have a survival of 70% without significant differences. We can affirm that lymph nodes metastases represent the most reliable marker of high risk patients among the 3 risk factors (grading, histotype and nodes metastases) even if considered on a limited number of patients on the basis of preliminary data so obtained. PMID- 3345783 TI - A new protocol for ovarian carcinoma. AB - We are presenting the actual protocol for ovarian epithelial carcinoma and we want to emphasize that a surgical procedure must be necessary, in almost all cases, with a double objective: one, staging accuracy of tumor spread and two, surgical treatment in its different modalities. Chemotherapy as adjuvant therapy becomes a primary treatment even in early stages. New drugs such as CDDP, Hexametilmelanine and epirubicin, associated in different proportions have improved the overall survival in ovarian cancer. Nevertheless there is a very good series in the response, when external radiotherapy to the total pelvis or to the total abdomen, is indicated. The best benefit in overall survival was obtained in stages III and IV when a combination of surgery, polychemotherapy including CDDP and irradiation was indicated. There is united agreement that the factor that influences decisively in survival is the size of the residual mass, and that independently of the indicated treatment. We must adjust the best type of surgery in order to remove the tumor mass localized in different areas. We think that this point is mandatory in order to get a good response with the adjuvant therapy association. PMID- 3345784 TI - Treatment of primary invasive cervical cancer. Considerations on 997 consecutive cases. AB - From 1965 to 1979 997 consecutive cervical cancer patients were treated at the University of Brescia. Stage I B and II A low risk patients underwent radical surgery, followed by Co60 external pelvic radiation when positive nodes and/or adverse pathological factors on the specimens were encountered. In stage I B the 5-year survival was 95.9% and 82.7% in the two groups and in stage II A 93.3% and 76.5% respectively. Bulky and large tumors were treated by intracavitary radium followed by radical hysterectomy and, if indicated, by Co60 external beam pelvic radiation. All other patients and all stage II B were treated by radiotherapy. The results of primary radical surgery may reflect the favourable preselection of cases. Postoperative radiation teletherapy in case of adverse pathological factors is of benefit to the patients. PMID- 3345785 TI - Optimal version of I and II stages vulvar carcinoma--surgical treatment. AB - In gynaecological clinic years during 1970-1986, 270 vulval carcinoma patients (I stage 12.6%; II 50.3%; III 29.3%; IV 7.8%) underwent treatment. 34.8% patients age was 60-69, 32.2% 70-79. Average age 66 years. In 70% patients diagnostic epidermoidal, 22.2% low differentiated cancer and 1 case (0.4%) adenocarcinoma. 187 patients underwent total vulvectomy (additional telecurie therapy 18 patients, 2 chemotherapy), 54 total vulvectomy + regional lymphadenectomy, 29 chemo (6), radio (3), symptomatic (20) therapy. 5-year recovery generally equated 40.1% (vulvectomy + lymphadenectomy 58.4%; vulvectomy only 35.8%), at I-II stage 52.1% (vulvectomy + lymphadenectomy 85.7%; vulvectomy 50.0%), at III stage 11.4% (vulvectomy + lymphadenectomy 42.9%; vulvectomy 6.7%), at IV stage 0%. T1 regional lymph nodes involvement, clinical signs (N1, N2, N3) were present in 24.1% patients, T2 36.1%, T3 70.8%. Out of marked 92 patients, lymphadenectomy was performed in 54, mainly with T1 and T2. Histological metastases observed in 48.1%, i.e. no more than 14% T1 and T2 patients. Considering the above raised question rised - it is justifiable in I and II stage patients with negative lymph nodes, regarding advanced age and concomitant diseases, perform protracted traumatic operation. But without histology it's hard to decide lymph nodes condition. Taking into account certain stage characteristic of metastatic spreading, in our clinic from 1985 in T1 and T2 vulval carcinoma without (N0) and/or with (N1, N2) regional lymph nodes involvement signs modified less traumatic one stage extensive vulvectomy with bilateral inguinal lymphadenectomy is performed. Suboperational morphological (cytology, histology) lymph nodes study is conducted. Upon metastases discovery dissection is carried out on femoral lymph nodes as wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3345786 TI - Receptor levels in breast cancer. AB - This report provides information regarding the relative importance of ER and PgR alone and both, as markers, in 352 breast cancers. We observed that the presence of ER not involves the presence of PgR, while the presence of PgR assumes an estrogenic action even if the lowest. In addition the presence of PgR+ depends also on ER negative-detectable (91.42% of the cases) such as we were able to observe that PgR+ was associated with ER negative-undetectable, only in 8.57% of cases. Moreover within the positivity of the couple of ER/PgR, the prognostic value is correlated at ER+ levels, while the predictive value is correlated at PgR+ levels. PMID- 3345787 TI - Breast cancer. A review of 144 cases. AB - From 1970 to 1980 144 cases of breast cancer were diagnosed in this Department. Patient's age varied between 25 and 83 years with an average age of 51.5 years. 49 (42.98%) patients were in fertile age and 65 patients (57.01%) were in menopause. The incidence of cancer increased after 41 years and the maximal incidence was between 51 and 55 years. Married (117; 81.45%) and pluriparous (75; 65.78%) women prevailed. In the pluriparous the average parity was 4, and 35 (30.70%) pluriparous had greater than or equal to 4 siblings. In 38 cases (27.08%) the patient was nulliparous. In 100 cases (69.64%) diagnosis was made without evident cutaneous alteration. Left and right breasts were affected in 73 (50.69%) and 68 cases (48.21%) respectively. Cancer was bilateral in 3 cases (2.08%). The most frequent cancer localization was ESQ (70 cases; 48.61%). 1st stage was diagnosed in 64 cases (44.44%), 2nd stage in 57 cases (39.58%) and 3rd stage in 23 cases (15.97%). The 5 year survival rate after operation was 86.79% (46 cases), 48.97% (24 cases) and 26.31% (5 cases) in patients at 1st, 2nd and 3rd stage respectively. 13, 8 and 4 patients were lost at follow-up. PMID- 3345788 TI - Radical vulvectomy and inguinal lymphadenectomy versus inguino-pelvic lymphadenectomy combined with radical vulvectomy and the role of radiotherapy. AB - We studied 39 patients with stromal invasion exceeding 1 mm. Among them 3 underwent emivulvectomy and 8 simple vulvectomy; all had selective inguinal lymphadenectomy of one side the first and bilaterally the others. 17 women underwent radical vulvectomy and inguinal lymphadenectomy while 11 had radical vulvectomy and inguino-pelvic lymphadenectomy. Out of 21 patients with lymph nodal metastases, 11 had one side inguinal metastases, 2 had a single metastasis, 2 had double metastases, 1 had three metastases and 2 multiple ones. Survival rate decreased from 54.5% to 20.0% when patients had more than 3 monolateral inguinal metastases or bilateral ones, with increase of pelvic lymph nodal metastases; therefore, in those cases, pelvic lymphadenectomy can be associated to inguinal lymphadenectomy or, when the carcinoma is situated in the clitoridis, Bartolino's gland or vagina (the same could be done for melanoma of the vulva). The usefulness of radiotherapy is limited by the small response of vulvar tissue. In a series of 45 patients with clinical diagnosis of inguinal metastases, who could not undergo operation, only therapy, with electron beam therapy (9 meV) associated to inguinal fields (15 meV), had positive influence in 27% of the cases. PMID- 3345789 TI - The ovarian teratomas. A histopathological review of 77 cases. AB - Seventy-seven cases of ovarian teratomas were studied according to examination modality of surgical specimens and to histologic patterns and frequency of different tissues components. The main histogenetic conjectures were debated also. PMID- 3345790 TI - Techniques of pelvic and para-aortic lymphadenectomy in the surgical treatment of cervix carcinoma. AB - 402 radical hysterectomies (17 ultraradical) were performed with lymphadenectomy. Positive metastatic nodes (N+) rate was 23.6% with an arithmetic mean of 22 excised lymph nodes. Single N+ belonged mostly to the obturatory group, double N+ to obturatory and external iliac groups, while multiple N+ (24 cases) had no particular site. Neoplastic invasion, embolism and grading were studied in 122 cases. The parametrium, vagina and uterine corpus were interested more in N+ cases. The cervical stroma was divided into internal, middle and external parts and invasion rate was respectively 3.6%, 7.2%, 89.2% in N+ cases and 35.1%, 22.3%, 42.6% in N--cases. PMID- 3345791 TI - Pathological problems of intraoperative diagnosis in sclero-elastotic lesions of the breast. AB - The Author describes pathological problems of the diagnosis, at frozen section, of non invasive lesions of the breast, classified according to "consensus meeting" on the preneoplastic significance of fibrocystic disease. Sclero elastotic lesions are treated with special interest and the main differential diagnoses are discussed. This lesion is considered to be benign and the relative risk of developing infiltrating carcinoma depends on the features of the epithelial component similar to fibrocystic disease whose sclero-elastotic lesion is likely to be a morphological variant. PMID- 3345792 TI - Induction of lymphocyte locomotor capacity by a substratum-dependent factor from mononuclear cells. AB - Media conditioned by human mononuclear cells contain a factor which renders freshly purified T lymphocytes motile and which is distinct from interleukin 1 and interleukin 2. The motility induced by this factor is morphologically indistinguishable from spontaneous lymphocyte motility. The factor is most effective when allowed to attach to the substratum. The effect of the factor on lymphocyte motility is detectable within 30 min but increases over a period of several hours. The relatively rapid action taken together with the ability to interact with both lymphocytes and the substratum point to the possibility that the factor rendering lymphocytes motile is a ligand which mediates cell-substrate adhesion. Attempts to characterize this putative ligand using gel filtration chromatography yielded activity peaks at 500 to 600 kDa. PMID- 3345793 TI - The induction of organ-specific antibodies during the graft-vs.-host reaction. AB - During the parent (P) into F1 hybrid graft-vs.-host reaction (GVHR), nuclear, leukocyte and erythrocyte autoantibodies are commonly seen. The specificity of these autoantibodies is reminiscent of those found in systemic lupus erythematosus (SLE) patients and SLE-prone mice. Organ-specific antibodies, however, including thyro-globulin (Tg) antibodies do not arise spontaneously. There have been conflicting reports about the ability of exogenous Tg to induce an anti-Tg response during the GVHR. We have re-examined this question in greater detail. Using the murine P----F1 GVHR system, the results of this work demonstrate that mouse thyroglobulin (MTg)-specific antibodies can be induced during a GVHR. However, mice must both be undergoing a GVHR, and have received exogenous MTg. The highest autoantibody response occurs if mice are injected with mouse thyroid extract or purified MTg at the time of P----F1 cell transfer. The anti-MTg response is MTg dose dependent. The ability to induce anti-MTg antibody was not major histocompatibility complex restricted, for both the DBA/2----B6D2F1 (low responder H-2 haplotypes to MTg), and AKR or DBA/2----AKD2F1 (high/low responder----high responder haplotype) GVHR gave similar responses. The anti-MTg titers peaked between days 7-10 and declined thereafter. In contrast, antibodies to dsDNA were not present at this early time, but developed after several weeks. We conclude that organ-specific autoantibodies can be induced during a GVHR if the appropriate antigen(s) are presented near the time of GVHR induction. PMID- 3345794 TI - Resistance of mouse cytolytic cells to pore-forming protein-mediated cytolysis. AB - Pore-forming protein (perforin, PFP) was isolated from a mouse large granular lymphocyte (LGL) [natural killer (NK-like)] cell line. Purified PFP lysed a variety of mouse tumor cell lines and helper T lymphocyte cell lines. However, LGL and cytotoxic T lymphocyte cell lines were resistant to PFP-mediated cell lysis. The presence of hemolytic activity in the granule was examined in these resistant cell lines. Four out of five of these resistant cell lines had hemolytically active granules. We determined whether NK cells freshly isolated from BALB/c nude mouse spleens were resistant to PFP-mediated cytolysis. Nylon column-passed spleen cells with an enriched content of NK cells exhibited more resistance than whole spleen cells. Moreover, when spleen cells were treated with PFP the remaining live cells showed enriched NK activity suggesting that normal peripheral cells with NK activity are resistant to PFP. These results indicate that cytolytic cells containing PFP have developed defense mechanisms to inhibit PEP-mediated cell lysis. PMID- 3345795 TI - Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. III. Cross-reactivity of bystander idiotopes on allergen-specific IgE antibodies. AB - Rabbits were inoculated with affinity-purified human antibodies to the common house dust mite Dermatophagoides pteronyssinus (DPT) to produce anti-idiotypic (Id) antibodies. The Id carried by human IgE antibodies were studied in a radioimmunoassay in which specific anti-DPT IgE were first insolubilized on rabbit F(ab')2 fragments against human Fc epsilon. In a single individual specific anti-DPT IgE antibodies shared bystander idiotopes (i.e. idiotopes located outside the antigen-binding site) with IgG antibodies of the same specificity, since the adsorption on insolubilized anti-DPT IgG almost completely eliminated the binding of anti-Id antibodies to IgE. This differed from our previous observations (J.-M. R. Saint-Remy et al., Eur. J. Immunol. 1986. 16: 575) wherein distinct paratope-associated idiotopes were identified on IgG and IgE anti-DPT antibodies. The frequency of cross-reactions between idiotopes of anti-DPT IgE antibodies observed in ten unrelated individuals was less than 10% for bystander idiotopes. This finding confirmed the private character of the above idiotopes that we found earlier on anti-DPT IgG antibodies. However, one anti-Id antibody preparation was found to react with bystander idiotopes of anti DPT IgE of most individuals, thereby suggesting the existence of a recurrent idiotope. The low frequency of inter-individual bystander idiotope cross reactivity contrasted with the public character of paratope-associated idiotopes. PMID- 3345796 TI - Subunits in zonulae adhaerentes and striations in the associated circumferential microfilament bundles in chicken retinal pigment epithelial cells in situ. AB - This study shows that the zonula adhaerens in chicken retinal pigment epithelial (RPE) cells in situ consists of independent subunits which are composed of extracellular intermembrane discs sandwiched between cytoplasmic plaques. These zonula adhaerens complexes (ZACs) are hexagonally arranged within the junction. Previous immunocytochemical studies suggest that the zonula adhaerens region, composed of ZACs, contains the actin associated proteins vinculin and alpha actinin. The intermembrane discs of ZACs likely mediate cell-to-cell adhesion whereas the cytoplasmic plaques are probably involved in binding the microfilaments of the relatively large circumferential microfilament bundles (CMBs), associated with the zonula adhaerens, to the cell membrane. The CMBs of chicken RPE cells in situ show striations similar to those found in stress fibers of other cell types and in CMBs of cultured epithelial cells. The observation that in the striated regions of CMBs the adjacent junctional membranes tend to follow an undulating path suggests that the CMBs are attached intermittently to the cell membrane and are contractile. The structural similarities between CMBs and stress fibers and the fact that they share similar actin associated proteins support the view that CMBs and stress fibers are related structures. PMID- 3345797 TI - Specific binding of lectins with the nucleus of the sea urchin embryo and changes in the lectin affinity of the embryonic chromatin during the course of development. AB - (1) Embryonic cells of sea urchins were made permeable by treating them with glycerol solution for the purpose of allowing penetration of macromolecules into the cell. With the use of such permeabilized cells, several kinds of fluorescent dye-labeled lectins were introduced into the cell, and it was found that some lectins showed notable affinity with the nucleus as compared with cytoplasmic structures. (2) Isolated chromatin was incubated with several kinds of fluorescent dye-labeled lectins in vitro, and the amount of lectins bound with the chromatin was measured by fluorometry. By means of this method, the lectin binding capacity of chromatin was estimated and compared at various stages of development. It was found that lectins could be classified into three groups according to the mode of binding with the chromatin: (a) Extent of binding increased notably at the gastrula stage (Con A and RCA-120); (b) extent of binding showed a temporary decrease at the gastrula stage (TTA); and (c) very low level of binding was maintained throughout all stages, and no particular change was observed at any stage of development (WGA, SBA, and UEA-I). (3) These facts seem to suggest that lectin-binding components are contained in sea urchin chromatin, and that drastic changes occur in these components of chromatin at the stage of gastrulation. It was proposed that the lectin-binding components such as proteoglycans and glycoproteins may play regulatory roles in embryonic chromatin at early stages of development. PMID- 3345798 TI - Introduction of definite amounts of nonpermeant molecules into living cells after electropermeabilization: direct access to the cytosol. AB - The possibility of introducing definite amounts of nonpermeant molecules into electropermeabilized living cells has been approached by quantifying the amounts of Lucifer Yellow (LY; a 457-Da highly fluorescent molecule) and Phytolacca americana (Pokeweed) antiviral protein (PAP; a 30,000-Da ribosome-inactivating protein) retained by the cells after closure of the electric-field-induced transient structures of permeation. Without the electropermeabilization, these two molecules enter the cell only in very small amounts by fluid-phase pinocytosis. Under our experimental conditions, using the NIH 3T3 cells, the intracellular LY concentration can reach a value equivalent to the extracellular concentration and can be regulated by controlling the external concentration. We describe the use of LY in a rapid and efficient test for the determination of the best electrical-shock conditions of other cell lines. After electropermeabilization, PAP is 2 X 10(5) times more cytotoxic. Its toxicity can be detected at external concentrations (10(-11) M) corresponding to less than 10 internalized molecules per electropermeabilized cell. Therefore, after electropermeabilization, the nonpermeant molecules have a direct access to the cytosol and the biological effect of nonpermeant substances can be revealed. PMID- 3345799 TI - Lymphocytes transfer only the lysosomal form of alpha-D-mannosidase during cell to-cell contact. AB - We have examined the changes in the activities of the different types of alpha-D mannosidase when fibroblasts from patients deficient in the lysosomal form of the enzyme are cultured together with normal lymphocytes. Our results show that whereas the mannosidosis cells acquired high levels of this enzyme, the activities of both the Golgi and the endoplasmic reticulum forms of alpha-D mannosidase remained the same as in the fibroblasts cultured alone in the absence of lymphocytes. The increase in the activity of the lysosomal enzyme in the cocultured fibroblasts was not affected by the presence of mannose 6-phosphate or alpha-methyl mannoside, inhibitors of receptor- and lectin-mediated uptake of lysosomal enzymes, respectively, but it did require cell-to-cell contact. Ion exchange HPLC and electrophoresis in polyacrylamide gradient gels showed that the acquired enzyme had the same elution profile and molecular size as the lysosomal form of the enzyme present in the lymphocytes. Immunoprecipitation studies using antibody specific for the lymphocyte type of lysosomal alpha-D-mannosidase confirmed that the increased activity in the cocultured mannosidosis cells resulted from the acquisition of the lymphocyte enzyme. Cytochemical examination revealed, however, that the transferred lymphocyte enzyme was localized in cytoplasmic organelles in the peripheral regions of the recipient fibroblasts. These results show that lymphocytes transfer only the lysosomal form of alpha-D mannosidase during cell-to-cell contact with mannosidosis cells. PMID- 3345800 TI - A simple technique for quantitation of low levels of DNA damage in individual cells. AB - Human lymphocytes were either exposed to X-irradiation (25 to 200 rads) or treated with H2O2 (9.1 to 291 microM) at 4 degrees C and the extent of DNA migration was measured using a single-cell microgel electrophoresis technique under alkaline conditions. Both agents induced a significant increase in DNA migration, beginning at the lowest dose evaluated. Migration patterns were relatively homogeneous among cells exposed to X-rays but heterogeneous among cells treated with H2O2. An analysis of repair kinetics following exposure to 200 rads X-rays was conducted with lymphocytes obtained from three individuals. The bulk of the DNA repair occurred within the first 15 min, while all of the repair was essentially complete by 120 min after exposure. However, some cells demonstrated no repair during this incubation period while other cells demonstrated DNA migration patterns indicative of more damage than that induced by the initial irradiation with X-rays. This technique appears to be sensitive and useful for detecting damage and repair in single cells. PMID- 3345801 TI - Preprophase bands in a suspension culture of the monocot Spartina pectinata. AB - Continuous suspension cultures of the marsh grass Spartina pectinata grow as either unorganized colonies or files of cells. Immunofluorescence of tubulin revealed microtubule (MT) structures similar to those encountered in meristematic cells, including cortical microtubule (MT) bands in some interphase cells and in all prophase cells. These MT bands were judged to be preprophase bands (PPBs) on the basis of their temporal appearance in the cell cycle and their position and orientation relative to division planes. Although PPBs are widely thought to be associated with organized tissues and polarized divisions, there are reports of PPBs in suspension cultures of four dicot species. This is the first report of a PPB in suspension cultures of a monocot species. PMID- 3345802 TI - Immunocytochemical localization of glucocorticoid receptors in cells, cytoplasts, and nucleoplasts. AB - A monoclonal antibody has been used to assess the intracellular localization of the glucocorticoid receptor in rodent L-929 fibroblasts and GH3 pituitary tumor cells. Whole cells from both cell lines showed immunoreactivity in the cytoplasm and nucleus. However, when cytoplasts and nucleoplasts of these cells were examined, only L-cells showed strong antibody binding in both fractions; in contrast, GH3 cells exhibited nuclear staining and slight cytoplasmic staining. These results are discussed in terms of the current findings regarding the intracellular location of steroid hormone receptors. PMID- 3345803 TI - Low Ca2+ stripping of differentiating cell layers in human epidermal cultures: an in vitro model of epidermal regeneration. AB - An in vitro model of the epidermal regeneration process is described. Incubation of multilayered, keratinizing cultures of human epidermal cells in Ca2+-free medium for 72 h results in a complete stripping of all suprabasal layers. When the Ca2+ stripped cultures are refed normal Ca2+ medium a reproducible series of morphologic and cell kinetic changes takes place. It is suggested that these changes represent a general pattern of regeneration after epidermal wounding. After an initial lag phase the regenerative response is principally effected by a recruitment to the proliferating pool of cells with a high rate of DNA synthesis. The cells seem to be programmed to rapid differentiation. Studies with cholera toxin suggest that this adenylate cyclase-stimulating agent is able to induce significant changes in the regenerative process causing a prolonged, but less intense, proliferative response leading to lateral growth rather than to rapid differentiation. PMID- 3345804 TI - Synchronization of replicons in Ehrlich ascites cells. AB - Ehrlich ascites cells, in which replication units at the beginning of the S phase started and grew synchronously, were obtained by the following protocol: (1) selection of G1 cells by zonal centrifugation, (2) hypoxia for 12 h, (3) reaeration, (4) addition of cycloheximide (30 microM) within the first minute after reoxygenation. Studies on the effectiveness of the different steps revealed: (i) G1 cells reoxygenated after 12 h of hypoxia traverse two succeeding cell cycles highly synchronously. This was shown by monitoring the thymidine incorporation rate, the thymidine pulse-labeling index, and the mitotic index. (ii) Cycloheximide, like hypoxia, suppresses replicon initiation in Ehrlich ascites cells without interfering with DNA chain growth and DNA maturation. The reversibility of the suppression is less complete than in the case of hypoxia. This was shown by DNA fiber autoradiography and by analyzing the length distribution of pulse- or pulse/pulse-chase-labeled daughter DNA in alkaline sucrose gradients. The alkaline sedimentation patterns of daughter-strand DNA, pulse labeled immediately after the cycloheximide addition at the end of the elaborated protocol and 1 and 2 h later, indicated synchronous initiation and growth of a homogeneous population of DNA molecules to replicon-sized lengths. PMID- 3345806 TI - State dependent activity in monkey visual cortex. II. Retinal and extraretinal factors in V4. AB - Responses were recorded from isolated neurons in the visual cortex of rhesus monkeys while they performed an orientation match to sample task. In each trial the animal was first cued with randomly selected orientation, and then presented with a sequence of gratings whose orientations were randomly selected. The animal was required to release a switch when it saw a grating that matched the cued orientation. For some recordings the animal was given a tactile cue by having it feel the orientation of a grooved plate that it could not see. In other experiments the cue orientation was presented visually on the screen in front of the animal and then removed before the sequence of gratings was presented. Using this task it was possible to determine if a neuron's response to a particular orientation was affected by whether or not it was the orientation for which the animal was looking. Over half the neurons examined in V4 (110/192) responded differently to the visual stimuli when the animal was cued to look for different orientations. For some neurons responses to all stimuli were strong when the animal was cued to look for a particular orientation, but weak when the same stimuli were presented in trials where the animal had been cued to look for another orientation. This type of sensitivity was found in neurons recorded while the animal was given a tactile cue, and also in other neurons tested when a visual cue was used, suggesting that the activity was not of direct sensory origin. In support of this, neurons in V4 were not strongly affected when the animal felt the grooved plate while not performing the orientation matching task. The prevalence of behavioral effects that was found using the orientation matching task suggests that extraretinal signals represent a prominent component of the activity in V4 of the behaving monkey. PMID- 3345805 TI - State dependent activity in monkey visual cortex. I. Single cell activity in V1 and V4 on visual tasks. AB - This study examined the extent to which the responses of single cells in the striate cortex (V1) and the extrastriate cortex (V4) of the alert rhesus monkey are modulated by visual stimuli whose relevance in a behavioral task is varied. The animal had to detect the repetition of a visual pattern (i.e. detect similarity), preceded by a randomized number of alternations between two different patterns. The responses produced by the last, reward contingent stimulus were compared with responses obtained to that same stimulus earlier in the sequence. Modulatory effects in V1 were moderate: 31% of the cells (63 of 200) showed response increments of 20% or more to the last, reward contingent stimulus. In V4 the effects were much more pronounced: 72% of the cells (110 of 154) showed modulatory effects of more than 20%. In V4 but not in V1 orientation tuning curves showed a significant narrowing as well as a peak response increment to the behaviorally salient stimulus, suggesting a feature specific mechanism associated with the detection of similarity. Although a response decrement was observed in many cells during the repeated alternations, this effect was significantly smaller than the modulation produced by the detection of similarity. Controls included the presentation of novel stimuli during the presentation sequence which did not produce an enhanced response. It is hypothesized that the feature specific effects reported here are produced by higher order feedback systems. PMID- 3345807 TI - 'Real-motion' cells in visual area V2 of behaving macaque monkeys. AB - Extracellular recordings were made in area V2 of behaving macaque monkeys. Neurons were classified into three groups: non-oriented cells, oriented cells with antagonistic areas and oriented cells without antagonistic areas in their receptive field. All neurons were tested with standard visual stimulations in order to assess whether they gave different responses to the movement of a stimulus and to the movement of its retinal image alone, when the stimulus was motionless and the animal voluntarily moved its eyes. To do this, neuronal responses obtained when a moving stimulus swept a stationary receptive field (during steady fixation) and when a moving receptive field swept a stationary stimulus (during tracking eye movements), were compared. The receptive field stimulation at retinal level was physically the same in both cases, but only in the first was there actual movement of the visual stimulus. Control trials, where the monkeys performed tracking eye movements without any intentional receptive field stimulation, were also carried out. Out of a total of 263 neurons isolated in the central 10 deg representation of area V2, 101 were fully studied with the visual stimulation described above. Most of these (83/101; 82%) gave about the same response to the two situations. About 14% (14/101) gave a good response to stimulus movements during steady fixation and a very weak one to retinal image displacements of stationary stimuli during visual tracking. We have called neurons of this type "real-motion cells" (cf. Galletti et al. 1984). None of the non-oriented cells was a real-motion one, while about an equal percentage of real motion cells was found among the oriented cells with and without antagonistic areas. Finally, we found only 4 neurons which showed behaviour opposite to that of real-motion cells, i.e. they showed a better response to displacement of the retinal image of stationary stimuli than to actual movement of stimuli. We suggest that real-motion cells might contribute to correctly evaluating movement in the visual field in spite of eye movements and that they might allow recognition of the movement of an object even if it moves across a non-patterned visual background. Present data on area V2, together with similar results observed in area V1 (Galletti et al. 1984; Battaglini et al. 1986), support the view that these two cortical areas analyse the movement in a parallel fashion along with many other characteristics of the visual stimulus. PMID- 3345808 TI - Sensory inputs to the agranular motor fields: a comparison between precentral, supplementary-motor and premotor areas in the monkey. AB - Kinesthetic responses of neurones in the motor cortex, including the primary motor (MI), the supplementary motor (SMA) and the postarcuate premotor (PMC) areas, were investigated in the awake, chronically prepared monkey. In all three subareas, neurones were recorded which responded to passive elbow flexions and extensions induced by a torque motor. In the SMA, such cells were restricted to its posterior portion where intracortical microstimulation produced limb and trunk movements. The majority of SMA cells responds to both displacement directions, a quarter to either flexion or extension. Although the total proportion of SMA neurones responding to arm displacements was low (15%), it was noted that in 'correct' somatotopic penetrations, the responsiveness could be prominent. The latency distribution of the kinesthetic responses was similar to that of MI neurones with slightly less response latencies shorter than 20 ms in the SMA. With manually applied stimuli, SMA neurones responded mostly to joint rotations, but not to light cutaneous stimuli. Only two SMA neurones with somatosensory responses were identified as descending projection neurones, and some neurones were found to be modulated also during active grasping. In the PMC, a higher proportion of neurones (27%) reacted to the standardized arm displacements, the majority again responding to both directions. The latency distribution of the kinesthetic responses was similar to that of SMA neurones. In contrast to SMA neurones, many PMC neurones responded to light cutaneous stimuli. It was found that some of the 'somatosensory' PMC neurones were sometimes driven also by moving visual and, rarely, by auditory stimuli. Although there are obvious differences in the nature and possibly also in the amount of sensory inputs to the three motor cortical areas, the present results indicate that all three subareas receive somatosensory feedback and that they might therefore all be implicated in the generation of sensory-driven motor output. PMID- 3345810 TI - Premotor cortex of rhesus monkeys: set-related activity during two conditional motor tasks. AB - We compared set-related premotor cortex activity in two conditional motor tasks. In both tasks, a rhesus monkey moved its forelimb to one of two possible targets on the basis of visuospatial instruction stimuli. One target was located to the left of the limb's starting position, the other to the right. In the directional task, a white light situated within the target provided the instruction. In the arbitrary task, colored instruction stimuli equidistant from the targets established an arbitrary relationship between stimulus and response. One hypothesis about set-related premotor cortex activity is that it contributes to the preparation for limb movement on the basis of sensory instruction stimuli. If set-related activity differed profoundly in the arbitrary and directional tasks, then that hypothesis would be untenable. Out of 403 task-related premotor cortex neurons in two monkeys, 130 neurons showed set-related activity, and we studied 118 cells in detail. The vast majority (81%) of these 118 neurons showed no significant difference between the two tasks in set-related activity. When set related activity did differ, the greatest activity usually occurred after arbitrary instructions; the opposite being the case for only 5% of our sample. Differences in activity during the two tasks, even when statistically significant, were generally small. The present results accord with the hypothesis that set-related premotor cortex activity reflects aspects of motor preparation. PMID- 3345809 TI - Influence of gravity on cat vertical vestibulo-ocular reflex. AB - The vertical vestibulo-ocular reflex (VOR) was recorded in cats using electro oculography during sinusoidal angular pitch. Peak stimulus velocity was 50%/s over a frequency range from 0.01 to 4.0 Hz. To test the effect of gravity on the vertical VOR, the animal was pitched while sitting upright or lying on its side. Upright pitch changed the cat's orientation relative to gravity, while on-side pitch did not. The cumulative slow component position of the eye during on-side pitch was less symmetric than during upright pitch. Over the mid-frequency range (0.1 to 1.0 Hz), the average gain of the vertical VOR was 14.5% higher during upright pitch than during on-side pitch. At low frequencies (less than 0.05 Hz) changing head position relative to gravity raised the vertical VOR gain and kept the reflex in phase with stimulus velocity. These results indicate that gravity sensitive mechanisms make the vertical VOR more compensatory. PMID- 3345811 TI - Rapid movements with reversals in direction. I. The control of movement time. AB - Modifications to the underlying motor control of rapid reversal movements (flexion-extension of the elbow) to accommodate experimentally induced changes in the movement time (MT) with constant movement amplitude were examined in man. MT was altered between conditions via instructions and feedback, resulting in seven distinct MT levels (from 100 to 250 ms to the reversal point) with essentially constant movement amplitude. As MT was decreased, the large increases in acceleration were met by two changes in motor control: (a) two- to three-fold increases in the peak accelerations and peak amplitudes of the agonist and antagonist EMGs, and (b) a systematic "compression" of the temporal structure of the entire acceleration-time and EMG-time patterns. This temporal "compression" with increased velocity caused by shifts in MT (distance constant) are considerably different from the constant-duration EMG bursts found when velocity is altered by changing movement distance (where MT is nearly constant). Our findings indicate that MT is a determiner of the temporal structure of rapid actions, and suggest that MT should be regarded as an important controlled variable, and not simply as an emergent property of variations in velocity. PMID- 3345812 TI - Rapid movements with reversals in direction. II. Control of movement amplitude and inertial load. AB - Transformations of the underlying movement control of rapid sequential (reversal) responses were examined as the movement amplitude (Experiment 1) and moment of inertia (Experiment 2) were altered, with constant movement time. Increases in amplitude and inertia were both met by sharply increased joint torques with a constant temporal structure, suggesting that the alterations may have been governed by a single gain parameter. The durations of various EMG bursts were essentially constant across changes in inertia, supporting a model in which the output of a fixed temporal representation is amplified to alter joint torques. The EMG amplitudes increased greatly with both amplitude and load. However, the fact that the EMG durations increased systematically with increases in distance provided difficulties for this model of amplitude control. The data suggest an economy in motor control in simple agravitational movements, whereby relatively simple transformations of an underlying representation can accommodate large changes in movement amplitude and moment of inertia. PMID- 3345813 TI - Partial attenuation of dentate granule cell evoked activity by the alternative substrates, lactate and pyruvate: evidence for a postsynaptic action. AB - Granule cell field potentials were evoked by stimulation of the perforant path of superfused hippocampal slices. Replacing the glucose in the superfusion medium with pyruvate (10 mM) or lactate (10 mM) attenuated the field potentials, significant decreases occurring in both the population spike and the population EPSP. Usually, a new steady state level of evoked activity was established which could be maintained for at least 20 min. Input-output analyses (EPSP vs stimulus strength, population spike vs EPSP) were performed using variable stimulus strengths on slices superfused with control or test media (under steady state conditions). At higher stimulus strengths the rate of rise of population EPSP was significantly lower for a given stimulus strength when pyruvate or lactate replaced glucose. However, the threshold stimulus intensity required to evoke a population EPSP was the same under all conditions. EPSP/population spike relationships were also analyzed under control and test conditions. Pyruvate, but not lactate, increased the threshold EPSP required to generate a population spike. Neither substrate significantly affected the incremental change in EPSP associated with a given increase in the population spike. It is argued that lactate and pyruvate attenuate granule cell evoked activity solely by postsynaptic actions. Lactate and pyruvate both appear to affect the summation of EPSPs; pyruvate may also affect the process of granule cell discharge. PMID- 3345814 TI - Centrifugal regulation of neuronal activity in the olfactory bulb of the waking rabbit as revealed by reversible cryogenic blockade. AB - The influences of centrifugal projections to the olfactory bulb were examined on the bulbar EEG and mitral-tufted cell activity in waking rabbits. Each of 6 rabbits was implanted, under surgical anesthesia, with fine wire electrodes for recording of the EEG and mitral-tufted cell unit activity and for stimulating the lateral olfactory tract. Two cooling probes, for reversible cryogenic blockade, were implanted on either side of the left olfactory peduncle. Records of EEG and unit activity were taken for 200 s before, during and after cooling of the probes to 3 degrees centigrade. Antidromic evoked potentials were used to assess the efficacy of the blockade. During the cryogenic blockade bursts of EEG activity, evoked in the bulb by inspiration through the nose, were augmented in amplitude and reduced in frequency. Mitral-tufted cell unit activity was reduced in rate but was more highly correlated with the phase and amplitude of the EEG bursts. Analysis of individual EEG bursts revealed that the variance in frequency of bulbar activity was significantly reduced in the isolated state. The data demonstrate that oscillatory bursting activity in the olfactory bulb is intrinsically maintained within a relatively fixed frequency range during receptor input and does not depend on centrifugal projections for its electrogenesis. Changes in EEG frequency, amplitude and correlation with unit activity support the hypothesis that centrifugal projections act in part to inhibit mitral-tufted cell output by direct excitation of granule cells. These findings are supported by a theoretical model in which distributed feedback to the granule cells from more central olfactory structures acts to regulate the coherency of bulbar activity. PMID- 3345815 TI - Local connections in transplanted and normal cerebral cortex of rats. AB - Injections of the fluorescent tracer Fluoro-Gold were made in transplanted and normal cerebral cortex of rats in order to investigate and compare the local connectivities of both. In the normal somatosensory cortex, small injections in superficial layers (I to III) produced retrograde cell labeling below the injection site in two bands: in layer V and in the deep part of layer VI. Pieces of embryonic rat neocortical tissue were transplanted into a cavity made in the somatosensory cortex of young adult rats. After a survival period of 2-3 months, small injections of Fluoro-Gold were made in the superficial part of the grafts. These injections revealed multiple clusters of intratransplant-projecting cells. No callosal or thalamic neurons were labeled in these experiments. On occasion, a bilaminated pattern of retrograde cell labeling was observed inside the transplants. In both transplanted and normal cortices, pyramidal and non pyramidal cells were retrograde-labeled. We conclude that in the neocortical transplants there is a pattern of local connectivity that is reminiscent of the pattern of intracortical connectivity in the normal neocortex in at least two aspects: first, the retrograde-labeled cells tended to form clusters or bands; second, both pyramidal and non-pyramidal cells were labeled. PMID- 3345816 TI - Eye-head coupling in humans. I. Simultaneous recording of isolated motor units in dorsal neck muscles and horizontal eye movements. AB - A tonic coupling between the horizontal component of eye position and dorsal neck muscle activity has been demonstrated in the cat and monkey. In order to demonstrate this synergy in humans and study its characteristics, we have measured the relation between the firing rate of individual motor unit of the splenius muscle and voluntary horizontal shifts of gaze using 5 degrees steps, in head-fixed subjects. Eye movement recording was achieved by conventional binocular electro-oculography and the activity of the right splenius muscle was recorded with Bronks coaxial bipolar electrodes inserted manually at the C4-C5 intervertebral level. The activity of 51 motor units in 10 subjects has been recorded. For all subjects, motor units firing rate increased when the gaze shifted to the ipsilateral side, and both increase in firing rate and recruitment were observed. These results demonstrate that the tonic eye head synergy is also present in man. PMID- 3345818 TI - Cortico-cortical connections of the limbic cortex of the rat. AB - By means of the retrograde transport of fluorescent tracers (Fast Blue, True Blue, Fluorogold and Diamidino Yellow), the cortico-cortical connections of prelimbic, insular, anterior and posterior cingulate (retrosplenial) areas have been studied. Our results demonstrate that there are, in the cortex of the adult rat, a few cells which have branched axons with connections in the ipsilateral hemisphere (associational neurons) or in the contralateral hemisphere (callosal neurons). The callosal neurons could be separated into two categories: "double callosal" neurons which project both axon collaterals to two cortical areas of the contralateral hemisphere, and "associational-callosal" neurons which send axon collaterals to both hemispheres. PMID- 3345817 TI - The role of auditory feedback in the vocalizations of cats. AB - The vocalizations of deaf cats were compared with those of littermate hearing controls at 30 days, 50 days, 1 year and 3 years of age. At all ages, deaf cats called more loudly than hearing animals. At 30 days, 50 days, and 3 years, deaf cats called about twice as loudly as hearing animals while at 1 year the calls of the deaf animals were approximately 6 times louder than those of the hearing littermates. Analysis of variance revealed significant differences in call loudness between deaf and hearing animals at 30 days, 1, and 3 years. Deaf and hearing animals did not differ in rate of calling or in the duration of individual vocalizations at 30 days, 50 days, and 1 year. At 3 years, the calls of the deaf animal were shorter than those of the hearing control. The calls of deaf animals were less variable than those of hearing animals at 30 days, 50 days, and 3 years. There was a tendency for the fundamental frequency of the calls of deaf animals to be higher than that of hearing animals at 30 days, 50 days, and 1 year. These results document the importance of auditory feedback in the regulation of feline vocalization. PMID- 3345820 TI - Human growth hormone in urine: development of an ultrasensitive radiometric assay. AB - An immunoradiometric assay for human growth hormone (HGH) has been developed which has a detection limit of 1 ng/l and can measure HGH in unextracted urine from normal children and adults. The assay is based on a two-step procedure, using a solid-phase goat-anti-HGH immunosorbent for immunoextraction and [125I] labeled monoclonal HGH-antibody for detection and quantification. The assay is not affected by urea, NaCl or changes of pH from 5-8. The mean urine HGH concentration in normal children is 6.78 +/- 7.6 (SD) pg/ml, in patients with HGH deficiency 1.3 +/- 0.9 pg/ml which increases to 11.7 +/- 13.4 pg/ml on the day of growth hormone injection. PMID- 3345819 TI - Do nigro-striatal neurones possess a discrete dendritic modulatory mechanism? Electrophysiological evidence from the actions of amphetamine in brain slices. AB - Dopamine released from dendrites of nigrostriatal neurones in the substantia nigra exerts an inhibitory action on these cells. However, the spatio-temporal characteristics of the action of dendritic dopamine is still unclear. The aim of the present study was to investigate the responses of these neurones in the guinea-pig to amphetamine, applied locally in the region of the distal dendrites in pars reticulata. During intracellular recording in vitro it was found that amphetamine hyperpolarizes the membrane and causes a decrease in the input resistance, probably by increasing a potassium conductance. This response was resistant to blockade of sodium channels but sensitive to dopamine depletion by reserpine and alpha-methyl-p-tyrosine. The response showed tachyphylaxis and proved to be highly dependent on the site of administration of amphetamine. It is concluded that the release and action of dopamine occurs locally, in a heterogeneous pattern, within the dendritic field of nigrostriatal neurones. The possibility is discussed that this phenomenon underlies a modulatory mechanism, localized in dendrites. PMID- 3345821 TI - Absorption of protein in the early postoperative period in chronic conscious dogs. AB - Postoperative alterations in amino acid exchange across the intestinal tract and in the capacity for protein absorption were investigated in a chronic canine model. Changes in postoperative splanchnic amino acid exchange consisted of a temporary decrease of total splanchnic amino acid release, including a significant reduction in alanine production, and an increase in glutamine consumption. Contrary to results under stable metabolic conditions, branched chain amino acids were also taken up by the intestine in the early postoperative period. The changes in postoperative amino acid exchange were not, however, reflected by a corresponding alteration in protein transport capacity. The absorptive capacity for a protein hydrolysate remained stable during the early postoperative period. PMID- 3345823 TI - Influence of ventilatory and circulatory changes on the pharmacokinetics of halothane and isoflurane. AB - In two groups of dogs, uptake and elimination of halothane and isoflurane were studied using a closed-loop anesthesia system which automatically controlled end tidal halothane or isoflurane partial pressure at minimal alveolar concentration (MAC) equivalent levels. Hemodynamic and respiratory variables were recorded and the anesthetic partial pressure was measured in the inspired and expired air, as well as in the arterial, cerebrovenous and mixed venous blood. Data were recorded during wash-in, hyperventilation, hypercirculation, hypotension and wash-out. For halothane, the controller delivered a higher inspired partial pressure than for isoflurane to compensate for the higher blood/gas partition coefficient. This was especially pronounced during the wash-in and the hypercirculation periods. Smaller differences between halothane and isoflurane partial pressures occurred during hyperventilation, hypotension and the wash-out period and could be explained by the lower solubility of isoflurane. These results show that even under unstable ventilatory and hemodynamic conditions, the inspired concentration of isoflurane has to be adjusted less often and to a smaller degree than that of halothane if end-tidal concentrations are to be maintained constant. PMID- 3345824 TI - Platelets and cardiovascular research: an introduction. PMID- 3345822 TI - Interaction of cortisol and epinephrine in the regulation of leucine kinetics in man. AB - To assess the interaction of the two major stress hormones epinephrine and cortisol in the regulation of leucine kinetics in man, epinephrine (50 ng/kg/min) was infused either alone or in combination with cortisol (2 micrograms/kg/min) into two groups of 6 postabsorptive normal male subjects during 180 min. Plasma leucine concentrations decreased by 28% (p less than 0.05) from baseline during epinephrine treatment (plasma levels 515 pg/ml); this was due to a decrease of leucine appearance (determined by 1-13C-leucine infusions) by 23% (p less than 0.025); leucine oxidation decreased by 29% (p less than 0.05). However, when plasma cortisol concentrations were elevated to supraphysiological levels (16.3 mumol/l) during epinephrine administration, the decreases of leucine plasma concentrations, appearance and oxidation were abolished. Plasma glucose and FFA concentrations were similarly elevated during both kinds of treatment. Since leucine appearance represents a measurement of total body protein breakdown and leucine disappearance into non-oxidative pathways reflects protein synthesis, the data indicate that plasma epinephrine concentrations during severe stress exert a protein anabolic effect in man which may counteract catabolic properties of elevated plasma cortisol. PMID- 3345825 TI - Thymidine-dependent effect of granulocyte-derived inhibitor on granulocyte macrophage progenitor cells (GM-CFC). AB - We have compared the effect of granulocyte extract (GRE) on proliferation of hemopoietic cells from various sources, using two different cultures media, CMRL 1066 and McCoy 5A. GRE caused a strong (80-90%) inhibition of granulocyte macrophage colony forming cells (GM-CFC) in cultures with medium CMRL 1066. GM CFC in human blood and human and mouse bone marrow were equally sensitive to the inhibitor. The inhibitor had a maximal effect in the concentration range corresponding to GRE from 2 x 10(5) to 2 x 10(6) cells per 1 ml culture dish. At higher GRE concentration the inhibition was reduced. GM-CFC from human blood and mouse marrow were suppressed in cultures with McCoy's medium as well, but to a lesser extent than in CMRL 1066 cultures. On the other hand, in cultures with human bone marrow cells (BMC) and McCoy's medium, GRE had no inhibitory effect. CMRL 1066 medium contains a number of components not present in McCoy's medium. In a systematic study where these substances were added one by one to McCoy's medium we found that inhibition by GRE depended upon the presence of thymidine. At a thymidine concentration of 3 x 10(-5) mol/l GRE strongly suppressed GM-CFC in human blood and bone marrow. This thymidine concentration itself had no effect. Other nucleosides or components of the CMRL 1066 did not potentiate the suppressive effect of GRE. PMID- 3345826 TI - Characteristics of circulating megakaryocyte progenitors (CFU-MK) in patients with primary myelofibrosis. AB - Characteristics of circulating CFU-MK and the effect of serum and plasma on CFU MK growth were studied in 14 patients with primary myelofibrosis (MF) using short and long-term culture methods. The number of CFU-MK in short-term cultures was significantly increased in the non-splenectomized patient group (p less than 0.01). Without added PHA-LCM and normal serum, spontaneous colony formation was found in 9 out of 10 patients. In long-term blood cultures from 6 MF patients, 3 untreated patients formed confluent adherent layers and produced in suspension an equal number or an even greater number of nucleated cells, megakaryocytes and CFU MK than those obtained in long-term bone marrow culture from normal individuals. 2 splenectomized patients showed neither an increased numbers of CFU-MK nor the capacity to develop an adherent layer. The serum and plasma of MF patients failed to stimulate megakaryocyte colony formation by normal bone marrow in a normal fashion. These findings indicate a megakaryocytopoietic abnormality, and a central role of the spleen in extramedullary haematopoiesis in MF. PMID- 3345827 TI - Red cell ferritin and iron stores in patients with chronic disease. AB - Serum and red cell ferritin were determined in a heterogeneous group of 59 patients with chronic disease undergoing a bone marrow biopsy. There was very little correlation between serum and red cell ferritin (r = 0.53). Although serum ferritin increased in relation to increased bone marrow iron stores, only 1 out of 8 patients with absent marrow iron stores and none of 8 patients with reduced marrow iron stores had a decreased serum ferritin. In contrast, 6 of 8 patients with absent iron stores had a reduced red cell ferritin concentration. There was no significant difference between the mean red cell ferritin of the patients with reduced, normal and mild-moderately increased marrow iron stores (30, 26 and 34 ag/cell). Red cell ferritin was decreased in 78% of a group of 32 patients with a low mean cell volume. In the patients studied, red cell ferritin was a better indicator of absent iron stores than serum ferritin. However, red cell ferritin did not detect a reduction in the iron status until the marrow iron stores were completely depleted. Apparently, during normal erythropoiesis the primitive erythroblasts continue to take up iron irrespective of the amount of iron available in the stores. PMID- 3345828 TI - Unexplained lymphadenopathy in sickle cell disease. AB - Progressive lymphadenopathy in a previously healthy female adult with homozygous sickle cell disease (SCD) was found to be due to infection with the human immunodeficiency virus (HIV). Detailed questioning identified several risk factors for HIV in this apparently low-risk patient. Parenteral therapy and heterosexual relationships while abroad may place such SCD patients at risk of HIV infection and its sequelae. The additional risk due to the underlying immunological abnormalities which have been identified in SCD patients is unclear in the absence of prospective studies or reported cases. PMID- 3345829 TI - Prognostic parameters in myelodysplastic syndromes: a multiple regression analysis. AB - The influence on survival of 21 basic clinical and hematologic parameters was evaluated in 72 patients with previously untreated myelodysplastic syndromes (MDS). Only five parameters were significant by both survival curves and multiple regression analyses: hemoglobin level, bone marrow (BM) cellularity (estimated from trephine BM biopsies), BM blast percentage, age and BM erythro/myeloid (E/M) ratio. Using these parameters, multiple regression analysis enabled us to predict 34% of the survival of all MDS patients (p less than 0.002), 38% of that of patients who had stable disease (p less than 0.04) and over 80% of that of patients who developed acute leukemia (p less than 0.02). High BM cellularity was the most predictive factor for the development of leukemia. No factor was predictive for patients who died of cytopenic or other complications. PMID- 3345830 TI - M-2 protocol for melphalan-resistant and relapsing multiple myeloma. AB - 33 patients with advanced refractory multiple myeloma received a combination of vincristine, cyclophosphamide, carmustine, melphalan and steroids (M-2 protocol). 20 of them had failed prior chemotherapy with alkylating agents and the remaining 13 patients had relapsed after a response to these drugs. An objective tumour cell mass reduction (greater than or equal to 50%) was achieved in 17% of the patients (6% of previously nonresponders and 33% of previously relapsing), while 9 additional patients improved (30-50% tumour reduction), for an overall response rate of 47% (39% for previously nonresponders and 58% for previously relapsing). The median duration of response was 7 months. Thrombocytopenia was the most common toxicity encountered in the study (39% of cases). Our findings indicate that M-2 protocol is an effective salvage treatment for patients who relapse from previous chemotherapy with alkylating agents. In contrast, results in patients who are primarily resistant to these drugs justify the search for different treatment programmes which can produce greater degrees of tumour reduction. PMID- 3345831 TI - Outcome of splenectomy in recessively and dominantly inherited hereditary spherocytosis. PMID- 3345832 TI - Similarity of protein conformation at low pH and high temperature observed for B chains of two plant toxins: ricin and mistletoe lectin 1. AB - A comparative study of subunits of two plant toxins, ricin (RC) and mistletoe lectin 1 (ML 1), has been undertaken. The study suggests that isolated B-chains of these toxins undergo structural transitions at low pH (from 5 to 4) and high temperature (45 degrees C), and as a result of the guanidine hydrochloride denaturing effect (to 3 M). Our results indicate that the protein conformation observed at low pH and high temperature are similar, though not identical. These conformations differ from the native one (pH 7, 25 degrees C), the protein in these conformations has a low fluorescence tryptophan intensity, and tryptophans are more exposed to aqueous solutions. However, these conformations differ also from the state unfolded by guanidine hydrochloride. An assumption is made that the partially denatured protein structure, exhibited at low pH and high temperature, is a functionally essential intermediate state of the toxin B-chain. PMID- 3345833 TI - Trapping the fast-refolding state of ribonuclease A at subzero temperatures. AB - Unfolded ribonuclease A consists of a mixture of fast- and slow-refolding species. It is generally accepted that the slow-refolding states arise from isomerization of proline residues. We show that unfolding at subzero temperatures may be used to trap the fast-refolding species Uf, since the rate of proline isomerization slows down at a much faster rate than protein unfolding. The unfolding was carried out in 5 M guanidine hydrochloride; at -15 degrees C the protein unfolding process is complete within 30 s and under these conditions there is less than 1.5% proline isomerization. By using ribonuclease in which Tyr 115 was nitrated it was possible to rule out significant isomerization of Pro-114 in the observed slow-unfolding step. PMID- 3345834 TI - Phorbol ester-induced protein kinase C translocation and lysosomal enzyme release in normal and cystic fibrosis fibroblasts. AB - The ability of the tumor-promoting phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) to induce protein kinase C (PKC) translocation and lysosomal enzyme release was examined in skin fibroblasts from normal subjects and from patients with cystic fibrosis (CF). As compared to normal fibroblasts, those CF exhibited: (i) an increased sensitivity to the effect of PMA on the disappearance of PKC from cytosolic fractions as well as a greater and earlier recovery, in the membrane fraction, of the PKC activity lost in the cytosolic fraction; (ii) an earlier response to PMA for its effect on beta-N acetylglucosaminidase release. In contrast, the inactive phorbol ester 4 alpha phorbol 12,13-didecanoate (4 alpha PDD) proved ineffective in inducing PKC translocation and beta-N-acetylglucosaminidase release in both normal and CF fibroblasts. The data suggest a defect in the regulation of PKC activity in CF fibroblasts, which may lead to altered secretion. PMID- 3345836 TI - Stimulation and partial stabilization of human histidyl-tRNA synthetase by hemoglobin. AB - Histidyl-tRNA synthetase, an enzyme against which antibodies are directed in some patients with polymyositis, has been purified 5000-fold from HeLa cells, but was extremely labile to dilution or on storage at -80 degrees C. In order to facilitate study of the biochemical and immunological properties of the enzyme, a stabilizer was sought. Hemoglobin at 2 mg/ml was found to stimulate the enzyme and also partially preserved the activity of the enzyme stored at a low concentration (less than 10 micrograms/ml). Hematin, but not the globin protein, could substitute for hemoglobin in stimulating the enzyme. PMID- 3345835 TI - The disulfide bridges of the immunoreactive forms of human pancreatic stone protein isolated from pancreatic juice. AB - Following the complete sequence elucidation of human pancreatic stone protein (immunoreactive form PSP S1 isolated from pancreatic juice) [(1987) Eur. J. Biochem. 168, 201-207], the location of the three S-S bridges of the protein was investigated. The cystine-containing peptides, detected after the separation of the peptic or chymotryptic digests on SP-Sephadex or Sephadex G-50, were submitted to Edman degradation and/or to oxidation. The cysteic peptides after separation on SP-Sephadex or Sephadex G-50 were characterized by their amino acid compositions. The pairing of the half-cystines: Cys 3-Cys 14, Cys 31-Cys 129 and Cys 104-Cys 121 was determined. The same experiments carried out with PSP S2-5 (other immunoreactive forms) gave an identical characterization. PMID- 3345837 TI - Glucose transporters in chromaffin cells: subcellular distribution and characterization. AB - The glucose transporter was identified and characterized by cytochalasin B binding in subcellular membrane fractions of chromaffin tissue. The binding was saturable with Kd of about 0.3 microM for each subcellular fraction. The Bmax capacity was 12-16 pmol/mg protein for enriched plasma membrane fractions, 6.3 pmol/mg protein for microsomal membrane preparations and 5.4 pmol/mg protein for chromaffin granule membranes. Irreversible photoaffinity labelling of the glucose protectable binding sites with [3H]cytochalasin B followed by solubilization and polyacrylamide gel electrophoresis from enriched plasma membrane preparations demonstrated the presence of three molecular species: 97 +/- 10, 51.5 +/- 6 and 30 +/- 4 kDa. The chromaffin granule membranes showed only a molecular species of 80 +/- 10 kDa. PMID- 3345838 TI - Do DNA polymerases delta and alpha act coordinately as leading and lagging strand replicases? AB - The activity ratio of DNA polymerases delta and alpha in calf thymus was found to be invariably 1:1, irrespective of extraction procedure (8 types) and subcellular localization (cytoplasm, nucleus and microsomes). This was established by separation of the two forms by hydroxyapatite chromatography and by their response to specific inhibitors and monoclonal antibodies. This finding supports the dimeric DNA polymerase model [(1980) J. Biol. Chem. 255, 4290-4303], which proposes that DNA polymerases delta and alpha act coordinately as leading and lagging strand enzymes, respectively, at the replication fork. PMID- 3345839 TI - Primary structure of the site on bovine hormone-sensitive lipase phosphorylated by cyclic AMP-dependent protein kinase. AB - The primary structure of a region on hormone-sensitive lipase was determined to be: Lys-Thr-Glu-Pro-Met-Arg-Arg-Ser- Val-Ser-Glu-Ala-Ala-Leu-Thr-Gln-Pro-Glu-Gly Pro-Leu-Gly-Thr-Asp-Ser-Leu-Lys. Ser-8 was the only residue in the intact protein phosphorylated by cyclic AMP-dependent protein kinase. However, Ser-10 also appeared to be present in a phosphorylated form, suggesting that it is a target for a distinct protein kinase in vivo. PMID- 3345841 TI - The importance of the phenyl-tropolone 'aS' configuration in colchicine's binding to tubulin. AB - Measuring ellipticities of (+/-)-colchicine and (+/-)-deacetamidocolchicine in the presence of tubulin afforded net positive CD bands with maxima at 340 nm resulting from reduction of the negative ellipticities upon binding of (-) enantiomers to the protein. Results of optical studies together with earlier NMR conformational analysis of these molecules substantiate the hypothesis that colchicinoids bind to tubulin with the phenyl-tropolone moiety in the 'aS' configuration. Natural colchicine which binds to tubulin, therefore, should be referred to as (-)-(aS,7S)-colchicine. PMID- 3345840 TI - Psoralen photofootprinting of protein-binding sites on DNA. AB - Using a BAL31 exonuclease assay to determine the sites of 4,5',8 trimethylpsoralen photocrosslinking in DNA we have shown that 5'-TA sites which are accessible to psoralen DNA interstrand photocrosslinking in naked DNA become inaccessible when protein, in casu, lambda-repressor E. coli or RNA polymerase are bound at their recognition DNA sequences (OR1 operator or deo1 promoter, respectively). These results show that psoralens can be used as photofootprinting reagents to study specific protein-DNA interactions. PMID- 3345842 TI - Interaction of site specific hirudin variants with alpha-thrombin. AB - The kinetics of complex formation between recombinant hirudin or recombinant hirudin mutants with thrombin were analyzed. In order to elucidate the inhibitor's reactive site peptide bond predetermined amino acid substitutions were introduced at positions of basic amino acid residues by means of site directed mutagenesis of a hirudin gene. In comparison to recombinant hirudin (Ki = 19 pM) only those mutant inhibitors which were modified at amino acid position Lys47 showed a higher Ki value for their complexes with thrombin. The observed effects are mainly due to increased koff rate constants. PMID- 3345843 TI - A model for the molecular mechanism of interfacial activation of phospholipase A2 supporting the substrate theory. AB - Changes occurring in the activity of porcine pancreatic phospholipase A2 upon formation of mixed micelles of sodium cholate and the fluorescent phosphocholines 1,2-di[6-(pyren-1-yl)butanoyl]-sn-glycero-3-phosphocholine or 1-[6-(pyren-1 yl)butanoyl]-2-[6-(pyren-1-yl)hexanoyl]- sn-glycero-3- phosphocholine were studied. A 2-fold enhancement was observed in the activity of phospholipase A2 towards both pyrene phospholipids upon exceeding the critical micellar concentration of the system. Changes in the pyrene excimer/monomer fluorescence emission intensity ratio coincide with the enhancement of phospholipase A2 activity at the critical micellar concentration. Due to the different effects of micellization on the alignment of the pyrene in the two fluorescent probes conformational changes could be assessed. A model describing possible conformations of these pyrene phospholipid molecules below and above the critical micellar concentration is presented and correlated with the interfacial activation of phospholipase A2. PMID- 3345844 TI - Calmodulin- and protein phosphorylation-independent release of catecholamines from PC-12 cells. AB - Catecholamine secretion from PC-12 cells can be triggered by agents that increase intracellular Ca2+ and is enhanced by phorbol esters and agents that elevate intracellular cAMP concentrations. In mutant PC-12 cells lacking cAMP-dependent protein kinase (PK-A) in which protein kinase C (PK-C) was down-regulated, Ca2+ dependent secretion occurred normally but was no longer enhanced by cAMP or phorbol esters. In digitonin-permeabilized PC-12 cells that lacked PK-C and PK-A, a range of calmodulin (CaM) inhibitors failed to block Ca2+-triggered catecholamine release. Moreover, Mn2+, a CaM activator, failed to trigger catecholamine release whereas Ba2+, which does not activate CaM, supported secretion. These results indicate that the basic mechanism of stimulus/secretion coupling in PC-12 cells does not absolutely require a regulated protein phosphorylation- or calmodulin-dependent step. PMID- 3345845 TI - Determination of three-dimensional structures of proteins from interproton distance data by hybrid distance geometry-dynamical simulated annealing calculations. AB - A new hybrid distance space-real space method for determining three-dimensional structures of proteins on the basis of interproton distance restraints is presented. It involves the following steps: (i) the approximate polypeptide fold is obtained by generating a set of substructures comprising only a small subset of atoms by projection from multi-dimensional distance space into three dimensional cartesian coordinate space using a procedure known as 'embedding'; (ii) all remaining atoms are then added by best fitting extended amino acids one residue at a time to the substructures; (iii) the resulting structures are used as the starting point for real space dynamical simulated annealing calculations. The latter involve heating the system to a high temperature followed by slow cooling in order to overcome potential barriers along the pathway towards the global minimum region. This is carried out by solving Newton's equations of motion. Unlike conventional restrained molecular dynamics, however, the non bonded interactions are represented by a simple van der Waals repulsion term. The method is illustrated by calculations on crambin (46 residues) and the globular domain of histone H5 (79 residues). It is shown that the hybrid method is more efficient computationally and samples a larger region of conformational space consistent with the experimental data than full metric matrix distance geometry calculations alone, particularly for large systems. PMID- 3345846 TI - Bisfunction of propionic acid on purified rat liver beta-ureidopropionase. AB - Propionic acid and isobutyric acid, which are structural analogues of N-carbamoyl beta-alanine and N-carbamoyl-beta-aminoisobutyric acid, respectively, acted as an allosteric activator as well as a competitive inhibitor of purified rat liver beta-ureidopropionase. Propionic acid and isobutyric acid had a Ki value of approx. 0.3 mM at pH 7.0. The Hill coefficient for N-carbamoyl-beta-alanine was 2.0, but the cooperatively decreased to 1.0 in the presence of 1 mM propionic acid. The K1/2 value towards N-carbamoyl-beta-alanine was calculated to be 0.17 mM from Hill plots and the Km value was determined to be 0.06 mM from replots of the apparent Km vs propionic acid. PMID- 3345847 TI - Resonance Raman evidence for an unusually strong exogenous ligand-metal bond in a monomeric nitrosyl manganese hemoglobin. AB - Resonance Raman spectroscopy has been employed to determine the vibrational modes of monomeric nitrosyl manganese Chironomus thummi thummi hemoglobin (CTT IV). This insect hemoglobin has no distal histidine. By applying various isotope labeled nitric oxides (14N16O, 15N16O, 14N18O), we have identified the Mn11-NO stretching model at 628 cm-1, the Mn11-N-O bending mode at 574 cm-1 and the N-O stretching mode at 1735 cm-1. The results suggest a strong Mn11-NO bond and a weak N-O bond. The vinyl group substitution does not influence the nu (Mn11-NO), delta (Mn11-N-O) and nu (N-O) vibrations. The Mn11-NO stretching frequency is insensitive to distal histidine interactions with NO, whereas the N-O stretching frequency is sensitive. Nitric oxide also binds to Met manganese CTT IV to form an Mn111. NO complex which undergoes a slow but complete autoreduction resulting in the Mn11.NO species. In manganese meso-IX CTT IV, the Mn111. NO Mn11. NO conversion alters the intensities of the porphyrin ring modes at 342, 360, 1587 and 1598 cm-1, but shifts the frequencies at 1504 and 1633 cm-1 (in Mn111.NO) to 1497 and 1630 cm-1 (in Mn11. NO), respectively. The unshifted marker line at 1378 cm-1 reflects the fact that the pi electron densities of the porphyrin ring are the same in the two complexes. PMID- 3345848 TI - Iron- and manganese-containing superoxide dismutases can be distinguished by analysis of their primary structures. AB - The iron- and manganese-containing superoxide dismutases have very similar three dimensional structures but can be distinguished by various biochemical means. The primary structures of six manganese-containing and three iron-containing superoxide dismutases are known. Analysis of the aligned amino acid sequences of these enzymes taken together with structural data from X-ray diffraction studies demonstrates that the two classes of enzyme can be distinguished on the basis of a small number of single-site substitutions that are positioned in and close to the active site of the enzyme. PMID- 3345849 TI - The ribosomes of Aspergillus giganteus are sensitive to the cytotoxic action of alpha-sarcin. AB - Ribosomes in lysates prepared from the mycelia of Aspergillus giganteus MDH 18894, which are actively secreting alpha-sarcin, do not contain the alpha-sarcin lesion. However, the addition of exogenous alpha-sarcin to these same lysates results in cleavage of the 26 S rRNA of the 60 S ribosomal subunit, characteristic of the cytotoxic action of alpha-sarcin. We conclude that A. giganteus ribosomes are not inherently resistant to the action of alpha-sarcin but are protected in vivo by producing alpha-sarcin in an inactive form and/or by the efficient cotranslational secretion of the toxin. PMID- 3345850 TI - A unique mRNA species for a regulatory subunit of cAMP-dependent protein kinase is specifically induced in haploid germ cells. AB - Cyclic AMP (cAMP) and its action by way of cAMP-dependent protein kinase is important for sperm motility. Previous studies on germ cells have demonstrated a selective decrease in the amount of type I cAMP-dependent protein kinase during spermatid development, and that type II was the major form present in elongating spermatids and in mature sperm. This would indicate activation of a gene in haploid germ cells, encoding a regulatory subunit of type II protein kinase. However, haploid expression of such a gene has so far not been shown. In the present study we demonstrate high-levelled expression of a unique mRNA species for a specific regulatory subunit of type II cAMP-dependent protein kinase at late stages of spermatogenesis, i.e. during spermatid elongation. PMID- 3345851 TI - Prognosis in node negative breast cancer patients: the importance of tumour diameter and mean nuclear area. AB - In node negative breast cancer patients, tumour size and mean nuclear area (MNA) as single variables have significant impact on prognosis. Combination of the two variables gives additional information on survival, and makes it possible to predict the outcome of the disease correctly in 70% of the patients both early (82 months) and late (154 months). MNA contributes relatively more to prediction of late prognosis than tumour diameter and vice versa for early prognosis. Thus a long follow-up is needed for node negative patients, and more so for patients with favourable prognostic criteria. PMID- 3345852 TI - Transcatheter embolisation to control severe bleeding in fungating breast cancer. AB - Severe and recurrent haemorrhage from ulcerating breast or skin lesions was controlled in seven of nine women with breast cancer. Arterial catheterisation and embolisation with a variety of materials (gelfoam, polyvinyl alcohol, steel coils, 50% dextrose) was used. Local anaesthesia only was needed, allowing very ill patients to be treated. This approach is the treatment of choice for severe haemorrhage in breast cancer. PMID- 3345853 TI - The Akiyama procedure in the surgical management of oesophageal cardiacarcinoma. AB - Currently subtotal oesophagogastrectomy with reconstruction of the digestive tract by use of a gastric tube appears to be the treatment of choice in patients with a carcinoma of the thoracic oesophagus and gastroesophageal junction. The results of 96 patients with a clinically operable oesophageal-cardiacarcinoma operated upon between 1977 and 1983 are reviewed. Resection intended for cure could be performed in 57 patients (59.4%). Twenty-five patients underwent a 'standard' Ivor Lewis procedure with an intrathoracic anastomosis, whereas in twenty-one patients the Akiyama technique with a retrosternal gastric tube and cervical oesphagogastrostomy was accomplished. There was a great shift in stage grouping from cTNM to pTNM. The major causes of mortality after oesophageal resection were respiratory and cardiac insufficiency (87% respectively 40% of the deaths) and sepsis from a mediastinitis caused by an intrathoracic anastomotic leak (20%). The postoperative mortality rate was similar in both procedures and amounted to 22.8%, but has decreased to 5% during the period 1983 to 1986. The 5 year survival rate for patients undergoing resections intended for cure was 20% as calculated by the actuarial method. There was no significant difference in long-term survival rates between the two resection groups. The late functional results were better in the cases with the Akiyama method, particularly where gastroesophageal reflux is concerned (P less than 0.05). PMID- 3345855 TI - The surgical treatment of gastric cancer: a retrospective study with special reference to total gastrectomy. AB - A retrospective study of 312 consecutive cases of gastric malignancy treated from 1974 to 1984 is presented. Eighteen patients (6%) had gastrointestinal lymphoma of the stomach. Among the remaining 294 cases with gastric carcinoma, 46 (16%) had carcinoma of the gastric stump after previous resection for peptic ulcer. Fifty-seven percent (167/294) had no distant metastases (MO). Early gastric carcinoma (pT1) occurred in 16 patients (5.8%), among whom four had distant metastases (pT1M1) and another two patients had regional lymph node metastases (pT1N1). Thirty-three percent of the patients had either no surgical treatment or an explorative laparotomy only, and 9% had a palliative bypass operation performed. A curative (48%) or palliative (10%) resection of the stomach was possible in 171/294 patients. Thus, the resectability rate was 58%. Total gastrectomy was performed in 108 cases with either curative (100) or palliative (eight) intention. The 30-day mortality was two and one patients, respectively (2.8%). Crude survival in the whole series was 16% and 11% at 5 and 10 years. After non-randomized curative total gastrectomy (100 cases) or gastric resection (40 cases) crude survival was 40% and 22% at 5 years, and 24% and 16% at 10 years, respectively (P greater than 0.05, n.s.). We found that total gastrectomy with extensive dissection and end-to-end esophago-jejunostomy by the EEA stapler can be performed with a low mortality rate (2% after curative operation) even in the upper age groups. PMID- 3345854 TI - Gallbladder cancer: current status in clinical practice. AB - A total series of 68 unselected patients with gallbladder cancer, diagnosed during 1972 to 1981, was studied retrospectively. In 61 cases (90%), the diagnosis was histologically verified. The cardinal symptoms were local pain (87%), loss of weight (53%), and jaundice (59%). The diagnosis was established after autopsy in 22 patients (32%), and exploratory laparotomy in 22 patients (32%). Palliative surgery was carried out in 26 patients of whom seven (27%) died postoperatively. Only one patient, with an incidentally detected cancer at routine cholecystectomy, was treated radically. Four out of nine patients died within one month after PTC-drainage. The mean survival time for the whole series was 2.9 months. The longest survival was 21 months. Considering the increasing incidence of gallbladder cancer in Sweden, as well as of other cancers of the biliary system, these findings emphasize the need for intensified research. An epidemiological approach studying the correlation of gallbladder cancer with the changing trend of gallstone disease and its treatment would perhaps be fruitful. PMID- 3345856 TI - Merkel cell tumour of the face successfully treated with radical radiotherapy. AB - A case of Merkel cell tumour of the face and its dramatic response to a course of radical radiotherapy is presented below. The patient has been free of recurrence for 18 months and has suffered minimal side-effects from the treatment. This suggests that radical radiotherapy, as opposed to the standard wide excision, may be the preferred first-line treatment for at least some of these rare, but highly malignant tumours. PMID- 3345857 TI - Malignant lymphomas and related conditions involving nasal cavity and paranasal sinuses: a clinicopathologic study of forty-two cases with emphasis on prognostic factors. AB - Lymphoproliferative diseases involving the nasal cavity and paranasal sinuses are uncommon and show complex histology, which make our understanding of the disease inadequate. In the present study, clinicopathologic findings, especially prognostic factors, in 42 patients with such diseases were reviewed. Histologically these cases were divided into ordinary lymphoma (23 cases) and a disease pattern that frequently showed a polymorphous picture containing large atypical cells with a non-lymphoid appearance (19 cases). The latter was termed midline malignant reticulosis (MMR) according to Kassel's classification. Clinically 'MMR' showed greater incidence of early onset of disease and higher male preponderance than ordinary lymphoma. The most common presenting symptom was nasal obstruction in both diseases. Favourable prognostic factors assessed by Cox's multivariate analysis were ordinary lymphoma (vs MMR), stage I disease, absence of ulceration in the lesions, and a tendency for local tumor formation. PMID- 3345859 TI - Enrichment experience for the institutionalized elderly. PMID- 3345858 TI - Revitalization: a developing approach to nursing care of the cognitively impaired. PMID- 3345860 TI - Caring for the chronically ill older adult at home. PMID- 3345861 TI - Neglect of the elderly. PMID- 3345862 TI - Medical ethics. 5.07 confidentiality: computers. PMID- 3345863 TI - Negligence in psychiatric practice. PMID- 3345864 TI - The prescribing habits of Delaware's physicians. PMID- 3345865 TI - Ontogeny of conditioned heart rate to an olfactory stimulus. AB - When heart rate is used as the index of conditioning, rat pups younger than 15 days of age do not display an odor-shock association. This constitutes a marked delay relative to the development of a somatomotor conditioned response. The incapacity to display autonomic learning to an olfactory stimulus prior to day 15 is not due to the inability to perceive and to orient to the olfactory stimuli used, nor to the inability to make unconditioned phasic cardiac changes. Rather, the late development of the heart rate conditioned response may indicate that the central neural mechanisms mediating heart rate conditioning are distinct from, and mature later than those mediating 1) heart rate orienting and 2) somatomotor conditioning. Evidence from studies in adult species is used to support these speculations. PMID- 3345866 TI - Stimulus attributes of reactivated memory: alleviation of ontogenetic forgetting in rats is context specific. AB - Numerous studies have shown that ontogenetic forgetting (infantile amensia) can be alleviated by a number of different types of reminder treatment. The present study extends the information about the alleviation of infantile amnesia by examining the "content" of the reactivated memory. Toward this purpose, one attribute of memory (environmental context) was examined in rats tested either shortly after training (preamnesic) or after 1-week retention interval. For the latter, a reactivation treatment was used to reverse infantile amnesia. At both intervals, a context shift resulted in impaired performance of a conditioned fear response. These findings demonstrate that environment context is an important component of the originally encoded memory as well as the reactivated amnestic memory. The implications of these results for both the reactivation of memory and general memory processes are discussed. PMID- 3345867 TI - Acquisition and retention of separate elements of a conditioned olfactory discrimination in preweanling rats. AB - Acquisition and retention of separate elements of an olfactory discrimination were tested in 15- and 20-day-old preweanling rats. Four or 8 conditioning trials were given in Experiment 1. Each rat was presented one odor always followed by footshock (CS+) and another never paired with footshock (CS-). Conditioning to both stimuli was assessed through 3 types of olfactory preference tests involving comparison between CS+ and a novel odor, CS- and a novel odor, or CS+ and CS-. The results indicated that for 15- and 20-day-olds, both stimuli become excitatory early in training; further conditioning trials diminished the excitation previously accrued to the CS-, and the olfactory discrimination became apparent. When levels of conditioning were equated, retention was tested after intervals of 4 min, 3 days, or 8 days (Exp. 2). Rate of forgetting was more rapid for the 15-day-olds, but both ages of subjects showed similar patterns of forgetting, which included a progressive decrease in the aversion to the CS+ but an increase in aversion to the CS-. PMID- 3345868 TI - Effects of age, sex, and psychological disturbance on immunoglobulin levels in the squirrel monkey. AB - The following research assessed the influence of developmental, hormonal, and psychological factors on immunoglobulin and complement protein levels in the squirrel monkey. A cross-sectional life span study established that the developmental pattern of immunoglobulins and complement proteins was similar to that observed in humans. IgG and IgM levels rose progressively with age, while the complement system was mature at birth. In contrast to humans, this species showed a significant sex difference in IgG levels, with higher levels in males during both infancy and adulthood. Males also showed a greater antibody response to viral challenge than did females, and evaluation of gonadectomized subjects suggested that the sex difference in antibody production was testosterone dependent. The effect of acute and sustained psychological disturbance on IgG levels was also evaluated in infant monkeys. Repeated, brief separations from the mother did not alter IgG levels, but IgG levels were suppressed after a 7-day removal from the mother. Therefore, despite the general view that immunoglobulin levels are relatively stable, these studies have established that immunoglobulin levels can be strongly influenced by hormonal and experiential factors in the squirrel monkey. PMID- 3345869 TI - Early experience influences adult retention of aversively motivated tasks in normal, but not DSP4-treated rats. AB - Sprague-Dawley rat pups were injected with DSP4 or water within 48 hr of birth and tested as adults in an inhibitory avoidance task and in a Y-maze discrimination reversal task. Half of the animals were also tested as juveniles during postnatal weeks 4-5, in tasks assessing odor preferences and general investigatory behavior. Controls, but not drug-treated adults, which received the juvenile testing, showed significantly better retention on both tasks than either controls or drug-treated animals not tested as juveniles. Neonatal DSP4 significantly reduced norepinephrine concentrations in the hippocampus and frontal cortex, but not the heart. The results suggest that central norepinephrine may modulate the effects of early experience on adult learning. PMID- 3345870 TI - Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis. AB - The association of hepatobiliary disorders with colonic inflammation is well recognized. Although the pathophysiology is obscure, increased permeation of toxic bacterial products across the inflamed gut to the portal circulation might be one mechanism. Potentially toxic metabolites include N-formylated chemotactic peptides that are produced by several species of intestinal bacteria and can be detected in colonic fluid in vivo. To investigate the metabolic fate of one of these low molecular weight proinflammatory peptides, N-formyl L-methionine L leucine 125I-L-tyrosine was introduced into colon loops of healthy rats (n = 10) and rats with experimental colitis (n = 15) induced by rectal instillation of 15% (vol/vol) acetic acid. Gut, liver, and blood radioactivity were monitored by external gamma-counting and radioactivity in bile was measured by biliary catheter drainage into a well counter. Bile was processed by high-performance liquid chromatography to determine the amount of intact, bioactive peptide excreted over 3 h. After colonic instillation of 1 nmol of peptide, the mean (+/- SEM) biliary excretion of intact peptide was 6.4 +/- 2.0 pmol in normal rats and 49.0 +/- 20 pmol in rats with colitis (p less than 0.01). An enterohepatic circulation of synthetic N-formyl L-methionine L-leucine L-tyrosine has been demonstrated in the rat. Experimental colitis was associated with an eightfold increase in biliary excretion of this proinflammatory bacterial peptide. Proinflammatory bacterial peptides synthesized by colonic bacteria could be important in the pathophysiology of colon inflammation and its frequently associated hepatobiliary complications. PMID- 3345872 TI - Spontaneous passage of glass beads from the canine gallbladder: facilitation by sphincterotomy. AB - To investigate the mechanism by which ablation of the sphincter of Oddi prevents gallstone formation, we assessed passage of glass beads out of the gallbladders of dogs with sphincterotomy and sham sphincterotomy. One month after bead implantation, dogs with an intact sphincter passed 52%, 26%, 22%, 10%, 0%, and 0% of beads with diameters of 2, 3, 4, 5, 6, and 8 mm, respectively. For the same respective bead diameters, dogs with a sphincterotomy passed 90%, 90%, 88%, 75%, 75%, and 42% of beads (p less than 0.05 for all bead diameters). No beads were in the common bile duct of any dog. In separate dogs studied by cholescintigraphy, sphincterotomy significantly increased gallbladder ejection fraction from 0.46 to 0.76 (p less than 0.01). In addition, sphincterotomy significantly lowered resting gallbladder volume from 24.4 to 15.8 ml (p less than 0.025) and lowered cholecystokinin-stimulated gallbladder volume from 13.3 to 5.9 ml (p less than 0.025). These data indicate that even with an intact sphincter, small solids can pass from the gallbladder and into the duodenum. Sphincterotomy facilitates passage of solids, apparently by general improvement in gallbladder emptying. Facilitated passage of crystals, microliths, or small stones seems the most likely explanation for prevention of gallstone formation by sphincterotomy. PMID- 3345871 TI - Effect of cholecystokinin receptor antagonist on pancreatic responses to exogenous gastrin and cholecystokinin and to meal stimuli. AB - Exocrine pancreatic response to food is believed to result from the interaction of neural and hormonal factors, but their contribution in the net postprandial secretion is unknown. Recent description of a highly specific and potent cholecystokinin (CCK)-receptor antagonist permitted the evaluation of the physiologic role of CCK in postprandial pancreatic secretion. In dogs with chronic pancreatic fistula, CCK antagonism caused little alteration in sham feeding- or urecholine-induced pancreatic protein secretion, but reduced by approximately 60% the pancreatic protein response to a gastrointestinal meal and virtually abolished the pancreatic responses to duodenal perfusion with amino acids or oleate and to exogenous CCK, but not to secretin or neurotensin. The pancreatic protein responses, particularly to lower doses of gastrin, were also reduced by CCK-receptor antagonist, but no changes in the responses to secretin or neurotensin were detected. Cholecystokinin antagonism also significantly reduced the pancreatic polypeptide responses to CCK, gastrin, and the gastrointestinal meal, possibly due to removal of the CCK-mediated release of pancreatic polypeptide. We conclude that CCK plays a crucial role in the mediation of the gastrointestinal phase, but not the cephalic phase, of pancreatic secretion. PMID- 3345874 TI - Liver hypermetabolism during alcohol withdrawal in humans. Role of sympathetic overactivity. AB - Catecholamines, which are elevated during alcohol withdrawal, can alter hepatic blood flow and increase hepatic oxygen consumption. We hypothesized that, in the withdrawal state, hepatic oxygen consumption and delivery could be altered in relation to an increased sympathetic activity. Thirteen chronic alcoholics were studied 34-72 h after withdrawal and 10 days later (control period) using conventional hemodynamic methods. As compared with the control period, splanchnic oxygen uptake was elevated at withdrawal (74.5 +/- 27.1 vs. 59.2 +/- 16.8 ml/min, p less than 0.025) and its variation was correlated with that of plasma epinephrine (r = 0.70, p less than 0.01). The hepatic venous oxygen content was reduced at withdrawal (113 +/- 22 vs. 126 +/- 21 ml/L, p less than 0.025) and correlated inversely with plasma norepinephrine levels (r = 0.56, p less than 0.01). We conclude that, during alcohol withdrawal in humans, hepatic energy expenditure may be elevated in relation to epinephrine secretion and that sympathetic overactivity may hinder the adaptive response in hepatic blood flow. The wide range in sympathetic nervous response to alcohol withdrawal could explain some differences in individual susceptibility to liver damage caused by alcohol. PMID- 3345873 TI - Regulation of the release of cholecystokinin by bile salts in dogs and humans. AB - The objective of these studies was to investigate the role of bile salts in the regulation of release of cholecystokinin in response to nutrients in dogs and humans. In dogs, the intraduodenal administration of a bile salt sequestrant, cholestyramine (2, 4, or 8 g/h), resulted in a dose-related enhancement of the release of cholecystokinin-33/39 and pancreatic protein secretion in response to intraduodenal administration of amino acids. Intraduodenal administration of cholestyramine alone did not affect basal levels of cholecystokinin-33/39 or pancreatic protein secretion. Total diversion of bile also significantly increased the release of cholecystokinin and pancreatic protein secretion in response to intraduodenal administration of amino acids. Replacement of the bile salt pool by intraduodenal administration of taurocholate completely reversed the enhancement effect of both cholestyramine and bile diversion. In humans, oral ingestion of cholestyramine (12 g) significantly increased the release of cholecystokinin-33/39 and gallbladder contraction in response to the oral ingestion of either a triglyceride or amino acids. These results support a physiologic role of bile salts in the negative feedback regulation of release of cholecystokinin in response to luminal nutrients. PMID- 3345875 TI - Etiology of portal vein thrombosis in adults. A prospective evaluation of primary myeloproliferative disorders. AB - In a prospective study of 33 adults with portal vein thrombosis unrelated to a liver tumor, we have assessed the prevalence of primary myeloproliferative disorders using conventional criteria and cultures of bone marrow progenitor cells. A primary myeloproliferative disorder was documented in 14 patients investigated at the time of recognition of portal vein thrombosis. Among these 14 patients, the main clue to the presence of the myeloproliferative disorder was (a) the observation of suggestive abnormalities of peripheral blood cell counts in 4 patients; (b) characteristic findings at bone marrow biopsy or determination of total red cell volume in 3 patients; and (c) formation of "spontaneous" erythroid colonies in cultures of bone marrow progenitor cells in erythropoietin poor medium in 7 patients. In 2 other patients, agnogenic myeloid metaplasia with myelosclerosis of apparently recent onset developed 5 yr after recognition of portal vein thrombosis. In conclusion, primary myeloproliferative disorders--in a full-blown or latent form, or at an early stage--are a major cause of portal vein thrombosis. PMID- 3345876 TI - Clinicopathological features of nonsteroidal antiinflammatory drug-induced small intestinal strictures. AB - The clinicopathological features in 4 patients are described where nonsteroidal antiinflammatory drugs appear to have caused small intestinal strictures. Two patients had rheumatoid arthritis and 2 patients had osteoarthritis; all had received nonsteroidal antiinflammatory drugs for 1.5-30 yr. Three patients had an initial illness characterized by diarrhea, profound weight loss, and hypoalbuminemia. Intestinal radiology at this stage ranged from subtle changes to those of Crohn's disease. Three patients underwent surgery. At operation the bland external appearance contrasted with the striking mucosal appearances of multiple concentric, circumferential, diaphragmatic strictures that caused luminal stenosis to a pinhole. These septa were due to submucosal fibrosis and the histopathological picture appears to represent a new nosological entity. PMID- 3345878 TI - Training and third-tier certification in gastroenterology. Training and Education Committee of the American Gastroenterological Association. PMID- 3345877 TI - Daily variations in the formation of gastric ulcers caused by cervical cord transection in the rat. AB - Cervical spinal cord transection is used as a model of mammalian stress ulcerogenesis. Circadian variations in gastric ulceration have been demonstrated in other animal models. We investigated whether gastric ulceration changed after cervical cord transection throughout a 24-h period by subjecting different groups of rats to cord transection. Ulcers were quantitated using an index described by Szabo and colleagues. Ulcer formation showed significant variation as a function of time of lesioning, with least severe ulceration at 8 AM. We found that cord transection, like other models of gastric ulceration, is also influenced by the circadian system. PMID- 3345879 TI - Colon cancer in ulcerative colitis. PMID- 3345880 TI - What is irritable esophagus? Another point of view. PMID- 3345881 TI - Sucralfate, smoking, and ulcer healing. PMID- 3345882 TI - Need for early thrombolysis in Budd-Chiari syndrome. PMID- 3345883 TI - Chylous ascites and esophageal sclerotherapy. PMID- 3345884 TI - Endoscopy for cancer in gastric ulcer. PMID- 3345885 TI - Free radicals and acute pancreatitis. PMID- 3345886 TI - Colorectal cancer in patients with ulcerative colitis. A population study in central Israel. AB - The incidence of colorectal cancer was studied in an unselected group of 1035 patients (total group) with ulcerative colitis and in a subgroup of 822 who resided, at the time of diagnosis, within a defined area in central Israel (regional group). The operation rate was 5.2% and the follow-up period (mean +/- SD) was 11.5 +/- 8.3 yr, range 1-52 yr. The cumulative incidence of colorectal cancer in all patients was 0.2% at 10 yr, 2.8% at 15 yr, 5.5% at 20 yr, and 13.5% at 30 yr. The ratio of observed to expected cancer was 0.9 at 10 yr, 5.0 at 20 yr, and 6.4 at 30 yr. The cancer incidence was 1 case per 3895 patient-years in the first decade of disease, 1 case per 198 patient-years in the second decade, and 1 case per 100 patient-years in the third decade. All these figures were higher in patients with total colonic involvement. There were no significant differences between the total and regional patient groups. Onset of ulcerative colitis in the first and second decade of life was not associated with a higher cancer incidence when standardized for extent and duration of disease. The risk of colorectal cancer in patients with ulcerative colitis was more strongly expressed in population groups with a lower incidence of this cancer. The cumulative incidence of colorectal cancer in ulcerative colitis is much lower in population-based studies than that reported from major medical centers. Worldwide this incidence may also vary among different populations. PMID- 3345887 TI - Spontaneous noncardiac chest pain. Evaluation by 24-hour ambulatory esophageal motility and pH monitoring. AB - Noncardiac chest pain can be a diagnostic dilemma because patients rarely experience spontaneous chest pain in the laboratory. Therefore, we studied 24 patients with chronic, daily, substernal chest pain with a prototype 24-h ambulatory esophageal motility and pH system. Spontaneous chest pain episodes were correlated with pH less than 4 and abnormal motility changes (mean amplitude and duration, maximum amplitude and duration, or percentage of abnormal peristalsis) defined as exceeding the patient's normal esophageal motility pattern. Twenty-two patients experienced a total of 92 spontaneous chest pain episodes. Eleven chest pain episodes (12%) occurred during abnormal motility, whereas 18 episodes (20%) were associated with pH less than 4 and four episodes (4%) had both abnormalities. The majority of chest pain episodes, 59 events (64%), did not have any association with motility or pH. Abnormal maximum duration and amplitude were the motility changes most frequently associated with chest pain. Overall, 13 of 22 patients (59%) had at least one chest pain episode correlating with abnormal motility or pH (range 33%-100%). Therefore, we conclude that ambulatory esophageal motility and pH monitoring is useful in the evaluation of noncardiac chest pain. pH abnormalities (20%) are more commonly associated with chest pain than motility abnormalities (12%). However, the majority of chest pain episodes (64%) did not correlate with either abnormality and may be the result of lowered esophageal pain threshold for distention, i.e., the "irritable esophagus." PMID- 3345888 TI - Day-to-day variation of 24-hour intragastric acidity. AB - Twenty-four-hour intragastric acidity was measured continuously using an intragastric electrode in 13 normal volunteers studied four times. Subjects were studied twice in the hospital and twice as outpatients. The dietary conditions were strictly controlled and the replicate studies were compared to assess the variability of such recordings of acidity. The accuracy of the technique was assessed, and a detection limit for differences was calculated for commonly used time periods. Over 24 h, during the night, during the day, and during the evening the technique is able to detect consistent changes of pH of greater than 0.1 units. During separate 5-min periods the limits of detection were considerably greater. This study demonstrates the variability of 24-h intragastric acidity and confirms that continuous monitoring is able to detect important changes of acidity under both hospitalized and ambulant conditions. PMID- 3345889 TI - Visceral myopathy of the gastrointestinal and genitourinary tracts in infants. AB - We describe 4 infants who had chronic intestinal pseudoobstruction caused by visceral myopathy. Three of the 4 were girls. Two were symptomatic at birth and 2 were symptomatic by 3 wk of age. All had abdominal distention and emaciation, 3 of the 4 had severe obstipation and fecal impactions, and 3 had signs of urologic obstruction. All had gaseous distention of the small bowel and colon, and barium studies showed dilated small bowel and colon, with slow transport through the small intestine. Two of 3 had enlarged stomachs and slowed gastric emptying, and 3 had dilated bladders and ureters. The 1 infant studied by esophageal manometry had absence of esophageal contractions. Despite total parenteral nutrition in 3, all died within 10-18 mo. The pathologic features of visceral myopathy were identified in variable sample sites from the esophagus, stomach, small intestine, colon, bladder, and ureter of the 4 infants. Of 170 family members related to 3 of the infants, there was no consanguinity and no one appeared to be clinically affected. Thus, an infantile form of visceral myopathy exists which, pathologically, is identical to the familial and sporadic forms of visceral myopathy previously identified in adolescents and adults. PMID- 3345890 TI - Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel. AB - A monoclonal antibody to bromodeoxyuridine was used in tissue specimens previously incubated with bromodeoxyuridine to show S-phase cells by immunohistochemical technique. Biopsy specimens of normal mucosa (n = 10), hyperplastic polyps (n = 10), adenomas with low-grade dysplasia (n = 20), adenomas with high-grade dysplasia (n = 10), and invasive adenocarcinomas (n = 10) of the large bowel were studied. Labeling index and cell proliferative patterns were analyzed. No statistically significant difference was found in labeling index between normal mucosa and hyperplastic polyps or between adenomas with high-grade dysplasia and adenocarcinomas. The labeling index was significantly lower in normal mucosa and in hyperplastic polyps than in adenomas and adenocarcinomas (p less than 0.001). The difference in labeling index between adenomas with high-grade dysplasia and low-grade dysplasia was also statistically significant (0.01 less than p less than 0.05). In normal mucosa and in hyperplastic polyps the proliferative zone was confined to the lower two-thirds of the crypt; no kinetic activity was found in the upper portions of the crypt or in surface epithelium. In adenomas the labeled cells were either present in the upper third or scattered along the whole axis of the crypt and in the surface epithelium. Labeling patterns in invasive carcinomas were similar to those observed in adenomas with high-grade dysplasia. The difference in proliferative patterns between hyperplastic polyps and adenomas supports a different significance of the two polypoid lesions in the histogenesis of large bowel cancer; our results confirm the subsequent steps of the adenoma-carcinoma sequence. Immunohistochemical labeling patterns observed with monoclonal antibody to bromodeoxyuridine in polypoid and cancer lesions of the large bowel are similar to those described by autoradiographic studies. PMID- 3345891 TI - There are no morphologic abnormalities of the gastric wall or abdominal vagus in patients with diabetic gastroparesis. AB - Because there is evidence for vagal autonomic neuropathy as the cause of diabetic gastroparesis, we hypothesized that this disorder should be associated with morphologic abnormalities of the abdominal vagus nerve or gastric myenteric plexus, or both. We studied the smooth muscle and myenteric plexus of the stomach in 18 nondiabetic controls and 16 patients with long-standing diabetes. Five of the diabetics had gastroparesis and 11 did not. We utilized conventional histology and Smith's silver technique for visualizing the myenteric plexus. Neurons within the myenteric plexus were quantified in sections stained with each technique. The abdominal vagus nerves from 5 diabetics (2 with gastroparesis) and 12 nondiabetic controls were stained with hematoxylin and eosin, Gomori trichrome, luxol-fast blue, and Holmes' silver stains. There were no abnormalities in the numbers or appearance of neurons or axons in the myenteric plexus of the stomach of diabetics, with or without gastroparesis. Also absent were abnormalities of the smooth muscle or vagus nerve. Thus, no morphologic abnormalities of the gastric wall or abdominal vagus were identified in diabetic gastroparesis. PMID- 3345892 TI - Role of nitrite and nitrate as a redox couple in the rat colon. Implications for diarrheal conditions. AB - Colonic levels of nitrite and circulating levels of nitrate are elevated in subjects with chronic diarrhea. The role of colonic epithelial cells in oxidation reduction of nitrite and consequent control of nitrite and nitrate levels is unknown. Isolated rat colonocytes and isolated loops of colon were used to study oxidation and reduction of nitrate and nitrite. Colonocytes oxidized nitrite to nitrate at a rate of 162 +/- 33 nmol/min.g (dry wt) (n = 6) over 0-20 min, a value increased by addition of 5 mM glucose and 1 mM nicotinamide adenine dinucleotide (p = less than 0.01), but not altered by antibiotics. Nitrite oxidation correlated linearly with the dry weight of isolated colonocytes (r = 0.92), indicating a cellular reaction. Nitrite was absorbed at a rate of 0.28 nmol/min.cm2 (n = 9) from the colonic lumen, which reflected 74% absorption of the available nitrite. Of the absorbed nitrite, 14.3% reappeared in the colonic lumen as nitrate. Colonocytes may be important in oxidizing nitrite to nitrate, thus preventing excess nitrite from entering into the circulation and returning some nitrate to the colonic lumen for respiration by anaerobic bacteria. The interaction of nitrites and colonocytes deserves further study with regard to the oxidation-reduction of nitrite and to the development of colonic neoplasia in chronic diarrheal conditions. PMID- 3345893 TI - Acid secretion and serum gastrin levels in individuals with Campylobacter pylori. AB - Campylobacter pylori may cause gastritis and has been proposed as an etiologic factor in the development of peptic ulcer. However, it may be an acid-sensitive microbe and before it can be implicated in the pathogenesis of peptic ulcer, it should be consistently found in ulcer patients with normal acid secretion. Thirty six patients with C. pylori by Warthin-Starry stain underwent gastric analysis; 25 were normochlorhydric and 11 hypochlorhydric. Ulcers were present in 19 normochlorhydric patients (10, gastric; 9, duodenal) and 2 hypochlorhydric patients (gastric). Median basal acid output was higher for those with duodenal ulcer (38 mmol/h) than gastric ulcer (28 mmol/h) or miscellaneous endoscopic features (33 mmol/h). The hypergastrinemia seen in 12 patients with negative secretin provocation tests was believed to be due to various nongastrinoma conditions. Campylobacter pylori was found in 6 normogastrinemic patients with elevated acid output and in 1 gastrinoma patient with marked acid hypersecretion. Histologic chronic gastritis was present in all subjects and 29 had active chronic gastritis. Twenty-three patients were taking H2-receptor antagonists at the time of diagnosis which did not seem to interfere with culture results. Using standard acid secretory tests, we conclude that C. pylori can survive in a wide range of acid conditions. PMID- 3345894 TI - Impaired colonic fermentation of carbohydrate after ampicillin. AB - The aim of this study was to investigate the effect of ampicillin on the ability of the human colon to ferment carbohydrate. The effect of ingesting a drink containing 20 g of lactulose on stool output and breath hydrogen production was measured in 13 normal volunteers before and during administration of ampicillin (2 g/day). Small bowel and whole gut transit times were also measured to exclude any direct effect of ampicillin on motor activity. Ingestion of lactulose did not increase stool weight or frequency under control conditions, but during administration of ampicillin, lactulose caused increases in stool weight (p less than 0.02) and frequency (p less than 0.01), in the percentage of unformed stools (p less than 0.001), and in the excretion of galactose and fructose in stool samples collected from 2 volunteers. Administration of ampicillin also significantly reduced the area under the breath hydrogen profile (p less than 0.03). Mouth-to-cecum transit of the lactulose drink was prolonged during ampicillin ingestion (p less than 0.01) but there was no significant change in the whole gut transit time. These results suggest that ampicillin impairs colonic fermentation of carbohydrate and a diet high in unabsorbable carbohydrate increases the risk of antibiotic-associated diarrhea. PMID- 3345895 TI - Osmotic effects of polyethylene glycol. AB - Polyethylene glycol (PEG) has been used to increase the osmotic pressure of fluids used to cleanse the gastrointestinal tract. However, little is known about its osmotic activity. To investigate this activity systematically, solutions of PEG of differing molecular weights were made and subjected to measurement of osmolality by both freezing point depression and vapor pressure osmometry. Measured osmolality was increasingly greater than predicted from average molecular weight as PEG concentration increased. Measurement of sodium activity in NaCl/PEG solutions by means of an ion-selective electrode suggested that the higher than expected osmolality could be due in part to interactions that, in effect, sequestered water from the solution. Osmolality was consistently greater by freezing point osmometry than by vapor pressure osmometry. To determine which osmometry method reflected biologically relevant osmolality, normal subjects underwent steady-state total gut perfusion with an electrolyte solution containing 105 g/L of PEG 3350. This produced rectal effluent that was hypertonic by freezing point osmometry but isotonic by vapor pressure osmometry. Assuming that luminal fluid reaches osmotic equilibrium with plasma during total gut perfusion, this result suggests that the vapor pressure osmometer accurately reflects the biologically relevant osmolality of intestinal contents. We conclude that PEG exerts more of an osmotic effect than would be predicted from its molecular weight. This phenomenon may reflect interactions between PEG and water molecules that alter the physical chemistry of the solution and sequester water from the solution. PMID- 3345897 TI - Effect of cold-induced pain on salt and water transport in the human jejunum. AB - The possibility that the central and autonomic nervous systems might be involved in the control of intestinal absorption was assessed by measuring the effect of physical stress (cold-induced pain) on jejunal transport in 13 healthy subjects. Using a triple-lumen perfusion technique to determine jejunal absorption, cold pain significantly reduced net water absorption from 34.9 to 15.7 ml/30 cm.50 min (p less than 0.005), net sodium absorption from 2.6 to 0.2 mEq/30 cm.50 min (p less than 0.005), and net chloride absorption from 2.2 to 0.6 mEq/30 cm.50 min (p less than 0.02). These changes were associated with an elevation of blood pressure and plasma norepinephrine during cold pain. During the period following cold pain, systolic blood pressure remained significantly elevated and net jejunal water absorption significantly reduced. These results suggest that physical stress can influence jejunal absorption of salt and water in humans and support the possibility that the central and autonomic nervous systems have a physiologic role in the control of intestinal function. PMID- 3345896 TI - Villous motility: relationship to lymph flow and blood flow in the dog jejunum. AB - Villous contraction frequency, lymph flow, blood flow, and arteriovenous oxygen difference were measured in dog jejunum. Venous pressure elevation and plasma dilution were used to increase capillary fluid filtration. Both perturbations produced concomitant increases in villous contraction frequency and lymph flow. A highly significant correlation (r = 0.83, p less than 0.001) was obtained between villous contraction frequency and lymph flow. This finding, coupled with the observation that stimulation of net fluid absorption increases villous contraction frequency, suggests that villous motility is increased by a myogenic response elicited by increments in interstitial fluid pressure. In another series of experiments local arterial pressure was reduced in 20-mmHg steps from 120 to 20 mmHg. Although blood flow fell proportionately to arterial pressure, villous contraction frequency and oxygen uptake were maintained at a normal level when arterial pressure was between 120 and 60 mmHg. Villous motility and oxygen consumption fell progressively as arterial pressure was reduced below 60 mmHg. This observation indicates that ischemia does not alter villous contraction frequency unless blood flow is reduced below the level necessary to maintain normal tissue oxygenation. PMID- 3345898 TI - Pharmacological properties of a new centrally acting muscle relaxant (NC-1200) in isolated muscle preparations. AB - 1. Pharmacological properties of a new centrally acting muscle relaxant (NC-1200) were tested in isolated muscle preparations. 2. NC-1200 acted as a Ca-blocker in the guinea pig taenia caecum. The pA2-value was 5.67. 3. In the rabbit aorta, NC 1200 competed with serotonin at serotonin receptors and also shifted the concentration response curves of histamine and norepinephrine suggesting the possibility that NC-1200 interacted with histamine and norepinephrine receptors. The pA2-value of NC-1200 against serotonin was 6.02. 4. There was no evidence that NC-1200 interacted with drug-receptors in the muscles except the rabbit aorta. 5. The present results are similar to the previous findings that the properties of serotonin, histamine and norepinephrine receptors in the rabbit aorta were different from those in other muscles. PMID- 3345899 TI - Supersensitivity to isoprenaline and epinephrine in right atria isolated from rats submitted to a single swimming session. AB - 1. The effects of swim-induced stress on rat atrial norepinephrine content, plasma corticosterone level and pacemaker sensitivity to catecholamines were studied. 2. Swimming for 50 min reduced the atrial norepinephrine content and induced a long-lasting increase in the plasma corticosterone level. 3. Pacemakers isolated from swim stressed rats showed supersensitivity to the chronotropic effect of isoprenaline. Sensitivity to norepinephrine was not significantly altered. Bilateral adrenalectomy or metyrapone pretreatment prevented the development of swimming-induced supersensitivity to isoprenaline. After in vitro denervation and addition of cocaine supersensitivity to epinephrine was demonstrated. 4. It is concluded that corticosterone, at least partially, mediates the supersensitivity to isoprenaline and epinephrine in pacemaker isolated from acutely swim stressed rats. PMID- 3345900 TI - Leucine-enkephalin- and neuropeptide Y-modulation of [3H]noradrenaline release in the oviduct of mature and juvenile rabbits. AB - 1. The effects of leucine-enkephalin and neuropeptide Y (NPY) on [3H]noradrenaline release induced by electrical field stimulation were studied in the isthmic part of the oviduct of juvenile and mature rabbits. 2. [3H]noradrenaline and total tritium overflow in the presence of cocaine, corticosterone and hyoscine were determined by liquid scintillation spectrometry. 3. Tritium overflow evoked by electrical stimulation (1 or 4 Hz, 1 msec) was calcium dependent. [3H]noradrenaline content (measured by ion exchange chromatography) accounted for 85% of the total tritium overflow. 4. Leucine enkephalin (1 microM) in the presence of the peptidase inhibitor bacitracin reduced the stimulation-evoked tritium overflow in mature rabbits by 26.1 +/- 1.6% and in juvenile rabbits by 11.9 +/- 1.9%. Naloxone (1 microM) antagonized the effect of leucine-enkephalin. 5. NPY (0.2 microM) reduced the evoked tritium overflow in mature rabbits by 23.4 +/- 2.4% and in juvenile rabbits by 17.2 +/- 4.3%. 6. It is concluded that leucine-enkephalin and NPY inhibited [3H]noradrenaline release in rabbit oviduct and the modulatory effect of leucine enkephalin depends on maturity while NPY modulation is a more independent system. PMID- 3345901 TI - Interactions of carbamazepine, chlormethiazole and pentobarbitone with adenosine on hippocampal slices. AB - 1. The effects of the anticonvulsants carbamazepine, chlormethiazole and pentobarbitone and their interactions with adenosine have been studied in rat hippocampal slices. 2. Neither chlormethiazole nor pentobarbitone changed the evoked population spike in CA1 stratum pyramidale, while carbamazepine produced a gradual decline of this potential at concentrations of 100 microM or greater. 3. This effect was not prevented by 8-phenyltheophylline. 4. Only carbamazepine (greater than 20 microM) produced any change of adenosine responses: a slowly developing reduction of the inhibitory action. 5. None of the anticonvulsants altered responses to the amino acid excitant N-methyl-aspartate, or kynurenic acid. PMID- 3345903 TI - The severely mentally ill in general hospital psychiatric units. AB - Analysis of data from the NIMH Survey of Discharges from Non-Federal General Hospitals found that severely mentally ill patients (those with schizophrenia, other psychoses, paranoia, and major affective disorders) became an increasingly larger proportion of general hospital discharges between 1970 and 1980, with more change observed between 1975 and 1980. This seems to confirm that general hospital care is replacing at least some of the care previously provided in State mental hospitals. There has been an increase in beds in nongovernment-owned general hospitals and a decrease in beds in state hospitals. In addition, while discharge referrals from government general hospitals for severe patients were made predominantly to state hospitals in 1970, in 1980 this was rarely the case. PMID- 3345902 TI - Influence of adrenergic and cholinergic mechanisms in baclofen induced analgesia. AB - 1. Baclofen induced analgesia was confirmed by means of the mouse hot plate test. 2. Physostigmine significantly increased the response to baclofen whilst neostigmine was ineffective. Baclofen analgesia was reduced by atropine. 3. The response to baclofen was increased by the administration of tolazoline, propranolol and nadolol. In contrast, the analgesic response to morphine was attenuated by the antiadrenergic drugs phenoxybenzamine, tolazoline and nadolol. PMID- 3345905 TI - A developmental-psychodynamic model for diabetic control. AB - This paper elaborates a psychodynamic-developmental model as a framework for understanding the wide range of adaptive and maladaptive responses to the self care requirements of diabetes. Early life experience participates with other factors in influencing the ease with which diabetics implement diabetic control. This model emphasizes the importance of the mother-child interaction during the second phase of development, the toddler phase, at which time the child begins to establish a sense of autonomy and control over his own body and its functions, with bowel training viewed as a paradigm for body control. It is postulated that certain types of mothers such as controlling-intrusive mothers, overprotective mothers, or guilty, indifferent, or rejecting mothers create problems for the child related to the development of autonomy and the sense of comfortable and pleasurable control over his bodily functions. Conflicts generated during this period are reactivated with the onset of diabetes and lead to difficulty in implementing control. In some situations where conflicts with the caretaker figure were predominantly limited to aspects of control, trusting relations acted as a substrate for change and improvement in control in a supportive medical environment. Specific management recommendations based upon this model are presented. PMID- 3345904 TI - Screening devices for diminished cognitive capacity. AB - This study compares three commonly used tests to detect organic mental disorders: the Mini-Mental State (MMS), Cognitive Capacity Screening Examination (CCSE), and Tachistoscope (T-Scope). Ninety-seven medical-surgical inpatients at the Mount Sinai Hospital referred for psychiatric consultation had a Missouri Mental Status Examination performed by a psychiatrist who also rated the patients' organic mental disorder as "none," "mild," "moderate," or "severe." The CCSE, MMS, and T Scope, respectively, showed: sensitivity--0.54, 0.52, 0.68; specificity--0.85, 0.76, 0.79; and positive predictive value--0.83, 0.74, 0.79. False negatives occurred more often among those patients with mild organic mental disorders with all instruments (p = 0.05), while the T-Scope could not be administered in 27% of the patients. Screening instruments with increased acceptability, sensitivity, and specificity need to be developed to identify a potentially life-threatening disorder. PMID- 3345906 TI - The psychodynamic formulation. How and why. AB - Medical students and psychiatric residents are often required to write psychodynamic formulations. Guidelines are given to accomplish this task, which include consideration of the precipitating event and the needs that are stimulated by it. Next, the regulating and mediating functions of the mind are discussed along with predisposing factors. Two clinical cases are presented and sample formulations are given. Finally, the author relates the psychodynamic understanding to the overall treatment of the patient. PMID- 3345907 TI - A psychiatric and neuropsychological study of patients with untreated Graves' disease. AB - We studied 13 untreated Graves' disease subjects in a clinical research unit using endocrine, psychiatric, and neuropsychological assessments. We used SADS interviews, RDC, standardized symptom rating scales, and motor activity monitoring to update earlier studies and quantified psychiatric symptoms to elucidate any correlations between endocrine and psychiatric status. Nine of 13 subjects had major depression, 8/13 had generalized anxiety disorder, and 3/13 were hypomanic. Anxiety levels were much higher than in other hospitalized medical patients. Using a broad battery of neuropsychological testing, we found mild deficits in attention, memory, and complex problem solving that were consistent with previous studies of hyperthyroid patients. The severity of psychiatric symptoms could easily result in an inappropriate referral to a psychiatrist prior to the diagnosis of hyperthyroidism. The relationship between psychiatric symptoms and possible CNS effects of excess levels of thyroid hormone is discussed. PMID- 3345909 TI - Treatment refusal in a rootless individual with medical problems. AB - A multidisciplinary case conference was held concerning an elderly woman who was hospitalized repeatedly because of progressive cardiac and pulmonary disease. The patient was unable to understand her illness and did not comply with the treatment regimen. The case demonstrates the usefulness of the multidisciplinary approach and the complexities of caring for someone who does not accept treatment. The dilemma is in how to preserve an individual's freedom and right to refuse treatment when organic impairment and past history interfere and pose a threat to health. PMID- 3345908 TI - Mood effects of alternate-day corticosteroid therapy in patients with systemic lupus erythematosus. AB - Mood and cognition were assessed on consecutive days in 18 female patients with systemic lupus erythematosus on alternate-day corticosteroid therapy. No overall differences in mood and cognition were observed between the on- and off medication days. However, 10 patients showed marked worsening or improvement of either depression or anxiety on their off-medication day. Two weeks of prospective behavioral ratings confirmed the observed mood changes in several patients. The clinical and theoretical implications of these findings are discussed. PMID- 3345910 TI - Reverse liaison rounds with a burn unit case. AB - A liaison rounds is presented, one attended by all members of a consultation liaison (C-L) team along with the medical director of a burn unit. This structure is designated as a "reverse liaison rounds," as it is the opposite of the conventional liaison meeting, which consists of one C-L consultant and the total nonpsychiatric team. The content centered on a self-inflicted burn case in which countertransference issues involved a nonpsychiatrist. The unconventional format of the reverse liaison rounds provided all parties with new knowledge, perspectives, and insights into the interactions between the C-L consultant and the burn unit team. PMID- 3345912 TI - The management of Parkinson's disease. PMID- 3345914 TI - The Parkinson's Disease Society. PMID- 3345915 TI - A suitable case for treatment? PMID- 3345917 TI - How long, o Lord, how long? PMID- 3345916 TI - Group life for the elderly mentally ill. PMID- 3345918 TI - Continuing education at night: Part 1. PMID- 3345911 TI - The process of dying. PMID- 3345913 TI - The physiotherapist's role in Parkinson's disease. PMID- 3345919 TI - Antioxidant RDA (recommended daily allowance) and supplements. PMID- 3345921 TI - Effect of normobaric hyperoxia on antioxidant defenses of HeLa and CHO cells. AB - The effect of increased intracellular oxygen activation on cellular antioxidant defenses in CHO and HeLa cells was studied. In both cell types, hyperoxic exposure (up to 4 days, 600-700 mm Hg O2) and in CHO cells menadione (up to 3 days, 15 microM) failed to affect the enzymatic antioxidant defenses Mn containing superoxide dismutase (Mn-SOD), CuZn-SOD, catalase and glutathione peroxidase. The markedly increased antioxidant enzyme activities observed in a recently obtained oxygen-tolerant CHO variant persisted under normoxia. These data suggest that the synthesis of antioxidant enzymes is constitutive. Glutathione levels of HeLa cells did not respond to hyperoxia whereas in CHO cells hyperoxia and menadione exposure resulted in a 2- and 7-fold increase in glutathione contents, respectively. However, considering the large variations in glutathione contents observed under normal culture conditions, it is uncertain whether this increase is to be considered as a true adaptive response. PMID- 3345922 TI - Visible chemiluminescence from rat brain homogenates undergoing autoxidation. II. Kinetics of the luminescence decay. AB - The visible luminescence emitted in the autoxidation of brain homogenates is only partially quenched when antioxidants are added at concentrations such that further oxidation is prevented. From the time course of the emission after antioxidant addition, it can be estimated that nearly 50% of the light arises from an intermediate that decays with a first order kinetics and with a lifetime of ca. 40 s at 32 degrees C. The remaining light arises from the decomposition of one or several intermediates, and show a kinetics that is independent of the incubation time. From the data obtained it is concluded that bimolecular free radical processes, such as the recombination of peroxy radicals, do not significantly contribute to the observed luminescence. PMID- 3345920 TI - Quantitation of intracellular oxidation in a renal epithelial cell line. AB - We quantitated the presence of intracellular oxidizing species in response to oxidative stimuli using fluorescent cell analytic techniques. The studies were performed with a laser-activated flow cytometry system using 2',7' dichlorofluorescin diacetate (DCFDA) as a probe for intracellular oxidation events. Oxygen radical formation was initiated by the addition of FeCl2 or xanthine oxidase to the culture media. Xanthine oxidase and FeCl2 both increased intracellular DCFDA oxidation over control (p less than .001). Increases in intracellular DCFDA oxidation in response to xanthine oxidase exposure were inhibited by extracellular superoxide dismutase, catalase and dimethyl sulfoxide (p less than 0.001), implicating the superoxide anion, hydrogen peroxide, and the hydroxyl radical in producing the changes in intracellular dichlorofluorescein fluorescence. Increases in intracellular DCFDA oxidation in response to xanthine oxidase correlated with loss of cellular viability, as established by decreased plating efficiency. We conclude that relative intracellular oxidation can be quantitated within the cultured renal cell and that some extracellularly generated radicals may be capable of traversing the intact cell membrane to oxidize DCFDA in the cell interior. PMID- 3345924 TI - Choledocholithiasis--in vivo stone dissolution using methyl tertiary butyl ether (MTBE). AB - We report a series of 10 elderly patients with large bile duct calculi refractory to standard endoscopic extraction techniques who were treated by gall stone dissolution using methyl tertiary butyl ether (MTBE) instilled through a nasobiliary catheter. In eight patients complete bile duct clearance was achieved after an average of eight hours MTBE instillation. In two patients gall stone size did not change. Both underwent operative gall stone removal and subsequent stone analysis showed low cholesterol content, which is unlikely to respond to MTBE. Apart from occasional transient nausea and drowsiness, no adverse reactions were noted. Methyl tertiary butyl ether appears to be a powerful in vivo gall stone dissolution agent which, from preliminary studies, is not associated with serious toxicity. PMID- 3345923 TI - Pancreatic Society of Great Britain and Ireland. 12th annual meeting. 6 November, 1987. Abstracts. PMID- 3345925 TI - Oesophageal function before, during, and after healing of erosive oesophagitis. AB - In order to investigate the relationship between oesophageal motor abnormalities and oesophagitis, we carried out four hour studies of oesophageal motility and 24 hour pH measurements in fasting and fed conditions in eight patients before, during (pH only), and after medical healing of erosive oesophagitis. Gastrooesophageal acid reflux decreased (ns) during the treatment, but tended to return to basal values at the end. Oesophageal body motility was unchanged after healing, while the lower oesophageal sphincter basal tone was significantly increased at the end of the study in the postcibal period. The results suggest that the impairment of the sphincter tone in reflux oesophagitis is secondary to the presence of the oesophageal lesions. Macroscopic healing is not paralleled by improved major pathogenic factors of the disease, however--that is, acid reflux and oesophageal body motility. PMID- 3345927 TI - Maturation of the lower oesophageal sphincter in the preterm baby. AB - There are few reported studies of the lower oesophageal sphincter in preterm infants and none has investigated babies of less than 34 weeks gestation. Using a modified manometric technique suitable for use on very low birth weight infants we have measured sphincter pressures on 68 occasions in 25 infants of postconceptional age between 27 and 41 weeks. In even the most preterm infants the lower oesophageal sphincter could be defined. The mean effective sphincter pressure rose from 3.8 mmHg in infants of less than 29 weeks gestation to 18.1 mmHg in the term infant. This rise in effective sphincter pressure correlated well with increasing postconceptional age (r = 0.81). This pattern of maturation in our patients was unaffected by intrauterine growth retardation, postnatal illness, or concurrent xanthine administration. PMID- 3345926 TI - Functional relationships between cricopharyngeal sphincter and oesophageal body in response to graded intraluminal distension. AB - Responses of the cricopharyngeal sphincter to graded intraluminal distension were studied in order to determine its response threshold and to define the functional relationship between the sphincter and oesophageal body. Nine normal subjects underwent manometric study using a multilumen tube with an attached inflatable balloon sited 10 cm below the sphincter. Sphincteric and oesophageal motor responses to six graded balloon inflations were recorded in each subject. The sphincter responded to distension with increasing rise in pressure, from a median value of 42.5 mmHg at lowest levels of distension to 95 mmHg at maximal tolerated distension. Non-swallow related contractile activity was stimulated in the oesophageal body proximal to the distension and increased in quantity as inflation progressed. Distal propagation of this secondary activity was progressively inhibited with increasing distension. These interrelated changes thus show the normal upper oesophageal clearance responses to intraluminal distension. It is suggested that their more widespread application, in addition to standard manometric techniques, might provide a more rational evaluation of those patients suspected to have impaired oesophageal clearance, but in whom standard manometry is non-diagnostic. PMID- 3345928 TI - Effects of osmoreceptor stimulation on human duodenal motor activity. AB - The motor responses of the human duodenum to saline solutions of varying osmolality were examined in order to investigate the possible role played by the upper intestine in the control of gastric efflux of hyperosmolar material. During fasting, delivery of the solutions into the duodenum increased duodenal motor activity and intraduodenal pressure, the magnitude of the response increasing with osmolality. At the highest osmolalities, a regular duodenal motor pattern was induced in some individuals which was indistinguishable from fasting phase III activity. After feeding, hyperosmolar saline again increased motor activity. In addition, the transit of an intraduodenal marker to the caecum was accelerated. These findings support the concept that the duodenum is both sensitive and responsive to its intraluminal content. The motor responses additionally appear to function to clear excessively stimulating intraluminal material from the duodenal lumen and may also contribute to the 'postpyloric' resistance which is known to exert control of normal gastric emptying. PMID- 3345929 TI - Raised plasma cholesterol precursors in patients with gut resections. AB - Cholesterol synthesis, faecal bile acids and neutral sterols, and plasma squalene and free and esterified cholesterol precursor sterols concentrations were studied in patients with previous ileal resection (n = 30) or jejunoileal bypass (n = 9) to elucidate the responses of different cholesterol precursors to enhanced cholesterol synthesis induced by cholesterol and bile acid malabsorption. A subgroup of seven resection patients without fat and bile acid malabsorption served as controls. Of the resection patients, eight had a pure bile acid malabsorption and 15 a combination of fat, bile acid, and modest cholesterol malabsorption. In the patients with jejunoileal bypass, cholesterol and fat absorption was greatly decreased in addition to bile acid malabsorption. The overall cholesterol synthesis was associated with proportionately increased plasma contents of free (and, less consistently, esterified) methyl sterols, the most marked increase, up to 18 times, being recorded for free and esterified lathosterols. The concentrations of the precursor sterols were similarly increased in the subjects with bile acid and cholesterol malabsorption, the two lathosterols showing the highest correlations with the overall cholesterol synthesis (r = 0.820-0.941). In the subjects with jejunoileal bypass cholesterol malabsorption effectively regulated cholesterol synthesis and the precursor levels. Gut exclusions large enough to cause cholesterol and/or bile acid malabsorption activate cholesterol synthesis leading to a proportional elevation in the plasma concentrations of cholesterol precursors, especially in those of lathosterols and free methyl sterols. Determination of the plasma concentration of total lathosterol by a single gas-chromatographic run is a suitable method for rapid screening of clinically significant cholesterol and bile acid malabsorption. PMID- 3345931 TI - Studies of the rectal mucosa in coeliac sprue: the intraepithelial lymphocyte. AB - The dynamics of the rectal surface epithelial lymphocyte and leucocyte response to wheat, gluten, and gliadin enema challenges in control individuals and in patients with coeliac sprue in remission is shown. There is a clear increase in intraepithelial lymphocytes and polymorphonuclear (PMN) leucocytes in response to these enemas in coeliac sprue, but not in controls. The peak response was at eight hours and cleared within 24 hours. There was no change in the crypt epithelium. These data add further support to the role of wheat, gluten, and gliadin in the pathogenesis of coeliac sprue, at least in the rectal mucosa. PMID- 3345930 TI - Intestinal permeability to polyethyleneglycol 600 in Crohn's disease. Peroperative determination in a defined segment of the small intestine. AB - Ileal permeability to different sized polyethyleneglycols (590-942 dalton PEG) was investigated peroperatively in 11 patients with Crohn's disease and seven with colonic carcinoma. A 15 cm ileal segment was converted into a tied loop, in which the PEG's were deposited. Absorption from the ileal segment was then measured as six-hour urinary recovery of the PEg dose. Polyethyleneglycol absorption in Crohn's disease was greater than in cancer patients and similar throughout the weight range, but in the cancer patients it was inversely proportional to molecular weight. Thus there was significantly greater absorption of the higher weights (greater than or equal to 678 dalton) in the Crohn's, than in the cancer patients. The apparently increased permeability of the small intestine in Crohn's disease may be an important factor in its pathogenesis. PMID- 3345932 TI - Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres. AB - A retrospective cohort of 823 patients with ulcerative colitis who resided at the time of diagnosis in one of three defined geographical areas (West Midlands region, Oxford region, England and Stockholm County, Sweden) was assembled. The patients were first seen at named hospitals in these areas and the diagnosis of ulcerative colitis established within five years of onset of symptoms between 1945-1965. All patients were 15 years of age or more at onset of disease and were followed for a minimum of 17 years and a maximum of 38 years. Ninety seven per cent completeness of follow up was achieved. Examining the colorectal cancer risk in the series relative to the risk in the general population by standardised morbidity ratios, there was an eight fold increased risk of cancer in the series as a whole. Dividing the series by extent of colitis, extensive colitis patients showed a 19 fold increase in risk. A four fold increased risk was shown in the remainder of the series (left sided colitis, proctitis and extent unknown). Life table analyses in extensive colitis gave cumulative risks of 7.2% (CI 3.6-10.8) at 20 years from onset of disease and 16.5% (CI 9.0-24.0) at 30 years from onset. No significant effect of age at onset, sex or referral centre could be detected. Examination of the data by interval from onset to cancer and by actual age at development of cancer suggests that patients who develop colorectal cancer will do so in a distribution around 50 years of age independent of duration of disease in adult onset ulcerative colitis (greater than 15 years at onset of disease). An inverse relationship was shown between age at onset of disease and interval from onset of disease to cancer. Further age specific rates for cancer increased up to 50 years and decreased thereafter. These results suggest that extensive colitis patients have a genetic predisposition to colorectal cancer and that longstanding inflammation is not of primary importance in the initiation/promotion of cancer in this disease. PMID- 3345933 TI - Sigmoid motility in diverticular disease and the irritable bowel syndrome. AB - Intraluminal pressures were measured with four open ended, water perfused tubes in the fasting state and after a standard liquid meal (400 KCal, 375 ml, protein 15 g, carbohydrate 55 g, lipid 13.4 g) in six patients with sigmoid diverticular disease, 20 with the irritable bowel syndrome and in 13 controls. The pressure sensors were positioned in the true sigmoid colon at colonoscopy at 25, 35, 45, and 55 cm from the anus. Colonic pressures were significantly higher in diverticular disease than in controls before (p less than 0.02) and after the meal (p less than 0.002), some pressure amplitudes exceeding 300 cm H2O. Patients with the irritable bowel syndrome had lower (p less than 0.05) pressures than controls before the meal. Postprandial sigmoid pressures were within the mean +/- 2 SD of controls in 10, above in two and below in eight patients with the irritable bowel. Hypercontractility of the sigmoid colon in the irritable bowel syndrome was not confirmed under the conditions of this study. The association between sigmoid diverticulosis and high intraluminal pressures is confirmed. PMID- 3345934 TI - In vitro mucus glycoprotein production by colonic tissue from patients with ulcerative colitis. AB - Colonic mucus production was measured in vitro by means of incorporation of tritiated glucosamine using biopsy material from patients with ulcerative colitis and compared with data from patients with Crohn's disease, colonic carcinoma, colonic polyps and patients with apparently normal colonic mucosae. Mucus production was significantly decreased (p less than 0.03) in all patients with ulcerative colitis, and in particular in patients with inactive disease when compared with normal subjects. In patients with active disease mucus production was not significantly different from normal subjects. The radiolabelled material was characterised by gel filtration and ion exchange liquid chromatography as mainly high molecular weight glycoproteins. These results indicate that the quantitative character of colonic mucus is abnormal in inactive ulcerative colitis. PMID- 3345935 TI - Functional abdominal pain, psychiatric illness, and life events. AB - Patients undergoing appendicectomy, attending a gastroenterology clinic or admitted to hospital after self-poisoning have been examined using the same reliable measures to establish whether life events and psychiatric illness preceded abdominal pain. Life events involving threat were experienced more commonly by those with organic and functional abdominal illness, compared with community comparison subjects. The greatest difference was with severe events, especially those involving the break-up of close relationships, which preceded the development of functional abdominal pain as often as they occurred before self-poisoning, and significantly more frequently than before the onset of organic gastrointestinal illness. Abdominal pain of recent onset, for which no organic cause is found, is often preceded by environmental stress, whether it presents to the surgeon or the physician. Those presenting in the clinic were older than those undergoing appendicectomy and had experienced more long lasting interpersonal difficulties. Many had psychiatric illness, but for the remainder the stress might either have caused colonic pain directly or led to consultation for abdominal pains that had not previously presented to a gastroenterologist. PMID- 3345936 TI - Communicating oesophageal duplication: a report of two cases. AB - Alimentary duplications which include a variety of alimentary cysts, diverticula and tubular malformations are rare abnormalities. Most of them, especially in relation to the oesophagus, do not communicate with the lumen. We present two very rare cases of communicating oesophageal duplication. Both are left sided and unassociated with any other congenital abnormality. These features again are uncommon with such duplications. PMID- 3345938 TI - A point of clarification. PMID- 3345937 TI - Fulminant herpes simplex hepatitis in a patient with ulcerative colitis. AB - A 16 year old girl with ulcerative colitis developed hepatitis with a high fever, leukopenia and a marked rise in serum transaminases without jaundice. There were no skin, oral, or genital lesions. Liver biopsy was precluded by abnormalities in coagulation. Postmortem examination of the liver by light and electron microscopy, culture, immunoperoxidase and immunofluorescent staining confirmed the diagnosis of hepatitis due to type 1 herpes simplex virus. Despite the rarity, this viral aetiology should be included in the differential diagnosis of all patients with severe hepatitis. The absence of mucocutaneous lesions should not exclude the diagnosis, especially when other clinical features are compatible. PMID- 3345939 TI - Start the year with a clean plate! PMID- 3345940 TI - Intravenous drug hazards: interactions, adsorption, and inadequate mixing. PMID- 3345941 TI - Welcome to our world. PMID- 3345942 TI - Elders versus caregivers: games they play. PMID- 3345943 TI - Creating an adult day care center. PMID- 3345944 TI - Paving the way to research in nursing homes. PMID- 3345945 TI - Promoting health for seniors. PMID- 3345946 TI - Structured learning for geriatric content. PMID- 3345947 TI - Pseudodementia. PMID- 3345948 TI - Combining skills for a common cause. PMID- 3345949 TI - Recurrent disease after negative second-look laparotomy in stages III and IV ovarian carcinoma. AB - Between 1977 and 1984, second-look laparotomy to evaluate disease status after adjuvant chemotherapy was performed in 134 patients originally presenting with advanced epithelial ovarian carcinoma. Surgical and histologic assessment did not detect persistent disease in 50 patients (37%). Recurrent carcinoma was subsequently documented in 15 patients (30%), all failures occurring within the abdominal cavity or the retroperitoneal space. Several patient subgroups at high risk for recurrence after negative second-look laparotomy are identified that might benefit from additional adjunctive therapy. Because of different treatment associated morbidities, the corresponding sensitivities and specificities of the high-risk groups may assist subsequent treatment selection. PMID- 3345950 TI - Absorbable synthetic mesh (910-polyglactin) intestinal sling to reduce radiation induced small bowel injury in patients with pelvic malignancies. AB - Absorbable synthetic mesh (910-polyglactin) was used to create an intestinal sling in six patients undergoing surgical staging of pelvic malignancies prior to radiation therapy. All patients had effective compartmentalization of small intestine out of the pelvis which persisted throughout the duration of radiation therapy. None of the patients developed complications related to the intestinal sling. This technique is well tolerated and has the potential to minimize chronic small intestinal complications caused by radiation therapy for pelvic malignancies. PMID- 3345951 TI - Serum alpha 1-acid glycoprotein in epithelial ovarian cancer. AB - Fifty-six patients with ovarian adenocarcinoma receiving chemotherapy were monitored with serum alpha 1-acid glycoprotein (AGP) levels. The mean and standard deviation of serum AGP levels for 63 healthy controls were 0.88 +/- 0.469 mg/ml. A serum level above 1.80 mg/ml was considered as above normal level. Five patients had evidence of persistent ovarian carcinoma and had elevated AGP levels. Sixteen patients had normal serum AGP levels and had no evidence of persistent ovarian cancer at second-look laparotomy. However, 35 patients had false-negative AGP levels at the time they had persistent tumor. Although the specificity of the AGP level was 100%, the sensitivity was only 12.5% and the overall accuracy 37%. Therefore, it would appear that serum AGP levels are not of value in monitoring patients with ovarian adenocarcinoma. PMID- 3345952 TI - Nonsquamous cancer of the vagina. AB - This report retrospectively analyzes 48 cases of primary vaginal cancer treated at Walter Reed Army Medical Center and the Naval Hospital, Bethesda, from 1962 through 1983. There was an unusually high number of uncommon histologic types. Nine patients had an adenocarcinoma, 5 had a sarcoma, 3 had a melanoma, 2 had an adenosquamous carcinoma, 1 had a lymphoma, and 1 had a carcinoid tumor. The remaining 27 patients had a squamous cell carcinoma. This represents a 43% prevalence of nonsquamous lesions. Nonsquamous cancer of the vagina occurred in patients at an earlier age than squamous cell carcinoma. Presenting symptoms, the location of the tumor within the vagina, and survival rates were similar for both groups. The clinical characteristics and treatment of the patients with nonsquamous tumors are discussed. PMID- 3345953 TI - Pelvic lymphocyst--a 10-year experience. AB - Pelvic lymphocysts occur infrequently after radical surgery for cervical cancer. The problem is one of recognition. In a retrospective analysis of patients seen over 10 years in this department, the incidence was 25.3%. All were diagnosed by bimanual, clinical examination only. The only factor that appears to relate to the formation of lymphocysts is the presence of poorly differentiated tumors; 70.8% of patients developing lymphocysts had poorly differentiated tumors. All the lymphocysts in this series resolved spontaneously and did not produce any major complications. PMID- 3345954 TI - Viral oncolysates in patients with advanced ovarian cancer. AB - Viral oncolysates (VO) derived from two cultured ovarian carcinoma cell lines infected with influenza A/PR8/34 were administered intraperitoneally (IP) to 40 patients with advanced ovarian carcinoma, including 31 with late-onset ascites and 5 with pleural effusions. PR8 virus-specific antigens and ovarian tumor associated antigens have been demonstrated on two oncolysates designated OVO1 and OVO2. Thirty-five patients received 9 mg of a 1:1 mixture of OVO1 and OVO2, 5 patients received one or the other. During the first month three IP schedules were evaluated, i.e., single, biweekly, and weekly, which were followed by monthly injections. Intrapleural (IP1) injections of a 3.0-mg 1:1 mixture of OV1 and OV2 were administered to 3 patients concurrently with initial IP injections and to 2 patients following later development of pleural effusions. In 7 patients ascites disappeared; in 5 of these the number of cytologically detected malignant cells was markedly reduced, in 1 pleural effusion disappeared, and in 3 tumor masses were reduced. Tumor masses shrank also in 2 patients without ascites. Tumor reduction conformed to standard response criteria in 2 of the 5 patients. Response duration in the 9 responding patients lasted from 3 to 19 months and survival durations 4 to 42 months. Disease symptoms in 7 patients improved noticeably. Two of the 9 responders later developed unilateral pleural effusions that responded for 7 and 15+ months to a single IP1 injection. Seventeen patients experienced one or more treatment side effects including fever, nausea or anorexia, malaise, abdominal pain, and arthralgia, but in only 2 patients, both on the weekly schedule, was toxicity severe enough to require treatment withdrawal. Humoral responses to viral and tumor cell-surface antigens were frequently observed in patients demonstrating clinical activity. PMID- 3345955 TI - Metastatic cerebral choriocarcinoma with primary neurological presentation. AB - Metastatic choriocarcinoma can present in bizarre fashions. Two cases with primary neurological presentations are reviewed. Cerebral metastases in choriocarcinoma generally denote a poor prognosis. However, in solitary metastases in the brain, craniotomy and excision followed by chemotherapy may be curative as illustrated by the following two cases. The first patient was diagnosed to have brain metastases 1 1/2 years after an evacuation of her molar pregnancy while the other patient developed cerebral choriocarcinoma 5 months following a spontaneous first trimester abortion. Both presented with neurological symptoms. Both patients are alive and well now, 9 and 5 years respectively after craniotomy and chemotherapy. A brief review of current considerations in the management of cerebral metastases in gestational trophoblastic disease is presented. PMID- 3345956 TI - Plasmacytoma of the ovary. AB - A plasmacytoma of the ovary in a 63-year-old is described. It was associated with an IgA K paraprotein. Myelomatosis developed 2 years after excision of the tumor. PMID- 3345957 TI - Lymphoceles following second-look laparotomy for ovarian cancer. AB - In patients treated for ovarian cancer it is crucial to distinguish recurrent malignancy from a benign process. Presented herein is a patient who developed bilateral pelvic lymphoceles following a second-look laparotomy for ovarian cancer. Indications for surgical intervention are discussed and the preferred surgical approach is outlined. PMID- 3345960 TI - Outdated data. PMID- 3345959 TI - The war within: a personal account of coping with systemic lupus erythematosus. AB - Coping with a serious illness is a hardship both for patients and their loved ones. In this article, insight into the seriously ill patient is provided through the chronicle of a sufferer of systemic lupus erythematosus. It is presented here for the benefit of social workers and health care professionals who may aid such patients. PMID- 3345958 TI - Clear cell ("mesonephroid") adenocarcinoma of the vulva arising in endometriosis: a case report. AB - A very unusual case of an apparent primary clear cell adenocarcinoma of the vulva in a 57-year-old female is presented. The carcinoma arose in an area of endometriosis within the canal of Nuck in the superior aspect of the right labium majus. Smooth muscle fibers presumably representing remnants of the extrapelvic round ligament were found associated with the endometriosis. Of interest is the fact that the patient underwent right herniorrhaphy 9 years earlier. Although several cases of primary adenocarcinoma arising within the vulva have been reported, none has arisen in areas of endometriosis within the canal of Nuck. No case in the literature of a primary clear cell adenocarcinoma arising from endometriosis in the canal of Nuck and in association with the extrapelvic portion of the round ligament could be found. PMID- 3345961 TI - "Medicalization" of community services for the elderly. AB - Research on medical care cost containment has indicated that the community-based service system is undergoing a process of restructuring within the context of an increasingly competitive environment and strong pressures to "medicalize" medical care services. PMID- 3345962 TI - Attributions of control by hip fracture patients. AB - Some hospitalized hip fracture patients assume responsibility for their accidents whereas others do not. Patients also differ in the control they project over their recovery and over future accidents. Patient's expressions of control may provide diagnostic clues and an avenue for social work intervention. PMID- 3345963 TI - Social work and the treatment of chronic pain. AB - The severity and prevalence of chronic pain is a growing concern for all health care professionals. An outpatient program that offered cognitive-behavioral coping skills training in a group setting was studied as a possible social work treatment for chronic pain patients, and the results were encouraging. Such treatments usually are available only in hospital pain clinics and research centers, which reduce treatment availability to patients in other settings. Social workers could provide services in a wider variety of settings to a large and growing population. As social workers realize the continuous interplay of physical, emotional, and cognitive factors in the experience of pain, they will identify appropriate practice roles for working with chronic pain patients. PMID- 3345964 TI - Maximizing effects of wellness programs for the elderly. AB - The authors studied 84 randomly selected participants who live in retirement communities to discover factors leading to successful completion of a wellness enhancing program. Four variables formed a discriminant function that correctly grouped 69 percent of participants. The authors discuss issues in identifying those most and least likely to benefit from wellness programs. PMID- 3345965 TI - Contribution of wood smoke to in vivo formation of N-nitrosothiazolidine-4 carboxylic acid: initial studies. AB - The effect of administering liquid smoke or smoked food products to rats on in vivo formation of N-nitrosamino acids was investigated. Rats treated by gavage with either cysteine, formaldehyde or nitrite excreted urine containing no detectable levels of N-nitrosothiazolidine-4-carboxylic acid (NTCA). All three precursor compounds were required for NTCA formation. Two liquid smokes, when administered to rats in combination with cysteine and nitrite also produced measurable quantities of NTCA. Ascorbate inhibited in vivo formation of NTCA by approximately 90% when given to rats simultaneously with cysteine, formaldehyde, and nitrite. alpha-Tocopherol was much less effective than ascorbate in blocking NTCA formation. When smoked bacon, smoked Swiss cheese, and chicken barbecued with a sauce containing smoke flavouring were fed to rats along with nitrate, NTCA was again detected in the urine. PMID- 3345966 TI - Subacute toxicity study of patulin in the rat: effects on the kidney and the gastro-intestinal tract. AB - Female and male Wistar rats were given drinking-water containing patulin at concentrations of 0, 24, 84 or 295 mg/litre citrate buffer (1 mM) for 4 wk. Compared with the controls, there were decreases in food and liquid intake by rats given the mid and high doses of patulin and the body weights of rats in the high-dose group were also decreased. The creatinine clearance in the high-dose group was lowered, although morphological glomerular damage was not observed. In the high-dose group, fundic ulcers in the stomach and enlargement and activation of the pancreatico-duodenal lymph nodes were noticed, while villous hyperaemia in the duodenum was observed in the mid- and high-dose groups. From the present data it can be concluded that high doses of patulin, administered via the drinking water, caused effects on the kidney and gastro-intestinal tract. Since no changes in the relative weight or histological appearance of the adrenal glands were observed, it is suggested that the fundic ulcers in the stomach were caused by a direct effect of patulin and not indirectly (i.e. by stress). PMID- 3345967 TI - Carcinogenesis in rats by cyclic N-nitrosamines containing sulphur. AB - The effects of chronic exposure to three sulphur-containing heterocyclic N nitrosamines were determined after repeated oral administration to female Fischer 344 rats. Nitrosothiazolidine did not significantly affect the survival of the rats or the incidence of tumours at a total dose of 3.5 mmol. Nitrosodithiazine, an analogue of nitrosothiazolidine which contains an extra sulphur atom inserted between the carbons of its CH2-CH2 moiety, produced only three tumours (two of the nasal mucosa) in a group of 20 rats at a total dose of 1.75 mmol/rat. Nitrosothialdine, the all-cis 2,4,6-trimethyl analogue of nitrosodithiazine, was a potent carcinogen that significantly shortened the lifespan and produced oesophageal tumours in 70% of treated rats as well as numerous tumours of the tongue and liver; this outcome was unexpected because alpha-methyl substitution in other heterocyclic nitrosamines usually reduces or eliminates tumorigenicity. The results extend the data base on the carcinogenic activity of molecules containing both divalent sulphur and the nitrosamino function. The lack of significant carcinogenicity of nitrosothiazolidine in this study suggests that its presence in the human food supply presents a relatively minor risk. PMID- 3345968 TI - The role of rat liver microsomal enzymes in the metabolism of the fungal metabolite fusarin C. AB - The metabolic activation of fusarin C by a rat liver microsomal monooxygenase resulted in the formation of a water-soluble mutagenic metabolite. However, fusarin C incubated in the presence of a microsomal preparation, but in the absence of an NADPH-generating system, led to the formation of fusarin PM1, a highly water-soluble compound which, like fusarin C, requires metabolic activation to be mutagenic. Enzyme studies using as substrates fusarins A and D, compounds structurally related to fusarin C, together with structural studies of fusarin PM1 indicated that fusarin PM1 was formed by the action of carboxylesterase which hydrolyses the C-20 methyl ester group to a free carboxylic acid. PMID- 3345969 TI - Pharmacokinetics of low doses of benzo[a]pyrene in the rat. AB - Intestinal absorption, bioavailability, hepatic and pulmonary extraction and elimination of low doses of benzo[a]pyrene (BP; 0.7-4.4 nmol) were studied in the rat using [G-3H]BP. The hepatic extraction ratio was 0.4 both in a liver perfusion model and in vivo as determined by comparison of intravenous and intraportal infusion experiments in anaesthetized rats. The pulmonary extraction ratio in vivo was 0.11 in control rats and 0.16 in rats pretreated with an inducer of cytochrome P-448. Analysis of BP concentrations in atrial blood and in the bile after continuous BP infusion into the duodenum of anaesthetized rats indicated that at least 30% of the dose must have been absorbed from the gut. Studies have also been performed in conscious rats given BP either as an intravenous bolus or by gavage. The bioavailability was determined to be about 10% in these experiments. Elimination proceeded in a triphasic manner with a half life of 16.6 hr for the terminal phase. PMID- 3345970 TI - Percutaneous absorption of Octopirox. AB - [14C]Octopirox administered to rats by intubation or injection was excreted mostly in the faeces (65-85% of the dose) with smaller amounts (6-19%) in the urine. Blood levels after intubation of Octopirox (4.8 mg/kg body weight) reached a maximum equivalent to 0.137 micrograms/ml at 2 hr and declined to 0.007 micrograms/ml at 48 hr after administration. Tissue levels were low, the greatest was the liver with the equivalent of 3 micrograms Octopirox at 6 hr after intubation. With female rats skin penetration of Octopirox at 1% (v/v) in shampoo without rinsing was 65.1 micrograms/cm2 under non-occlusive conditions for 48 hr. When the skin was rinsed after a 10-min contact, penetration was reduced to 3.4 micrograms/cm2 under occlusive, and 2.0 micrograms/cm2 under non-occlusive conditions. Skin penetration of Octopirox was dependent on duration of contact up to 10 min before rinsing. Penetration at 1% Octopirox increased significantly from 2.4 micrograms/cm2 after 2.5 min exposure to 4.5 micrograms/cm2 after 10 min contact, but there was no further increase in penetration with a 20-min application. Skin penetration and deposition of Octopirox were both proportional to Octopirox concentration between 0.1 and 1% (w/v); skin penetration increased from 0.31 to 3.6 micrograms/cm2 while deposition increased from 0.8 to 7.6 micrograms/cm2. There was no significant difference between the penetration through clipped skin and hairy skin from an application of 1% Octopirox for 5 min followed by rinsing. Under non-occlusive conditions, penetration was 1.5 micrograms/cm2 for both types of skin. Blood levels after topical application (15.4 mg/kg body weight) without rinsing and with occlusion reached the equivalent of 0.32 micrograms/ml at 6 hr. However, when the skin was rinsed and protected with a non-occlusive patch blood levels were reduced to a maximum equivalent to 0.02 micrograms/ml at 1 hr after application. The safety factor estimated for the consumer using a shampoo containing 1% Octopirox is 29,400, so that the possibility of systemic effects due to absorption through the skin is remote. PMID- 3345971 TI - A critical evaluation of a dose-response assessment for TCDD. PMID- 3345972 TI - [Tobacco smoke and the development of emphysema]. PMID- 3345973 TI - [Structural correlation of schizophrenic thought and language disorders with delusional perception and variations of intentionality]. AB - This study originated from a phenomenological and speech-act theoretical concept of schizophrenic concretism. An experimental study was performed showing a highly significant lack in the schizophrenic patients' ability to use metaphors correctly. Basing on the interpretation of proverbs, the hypothesis is rejected that false interpretations of schizophrenic patients are due to intermingling of personal conflicts. On the other hand, it could be shown that concretistic interpretations of proverbs represent an avoidance of conflicts. The concepts of "substitution" and "transfer" enabled us to measure pathological concreteness and "deconflictualisation". The differentiation between schizophrenic and nonpsychotic patients was found to be highly significant. In a complementary study it could be shown that the chronic schizophrenics' disability to transfer images of proverbs to an interpersonally relevant context does not differ significantly from that of patients with their first schizophrenic episode. Discussing our empirical findings, we try to show that the concretistic reduction of thought and speech is also a paradigma of delusion. The "incorrigibility" of schizophrenic delusion was seen to be based on reification of verbal signs and metaphors. After trying to show a connection between the concretistic "Lebensform" (Wittgenstein) and the disordered intentionality of schizophrenic patients, pointers towards psychotherapeutic implications are given. PMID- 3345974 TI - Nursing homes are not the answer. PMID- 3345975 TI - Treating elderly chronic patients in state hospitals. PMID- 3345976 TI - Transient patients in a western state hospital. PMID- 3345977 TI - Limitations on HMO services and the emerging redefinition of chronic mental illness. PMID- 3345978 TI - Occupational therapy: functional assessment of the severity of mental disorders. PMID- 3345979 TI - Stress and coping in relatives of burn patients: a longitudinal study. AB - Standardized psychological assessment of 48 close relatives of patients hospitalized for burns revealed that the relatives experienced high levels of distress during the acute phase of the patient's hospitalization. At six-month follow-up, the relatives' general psychological symptomatology had receded to within the normal range, but 25 percent continued to show specific stress syndromes characterized by intrusive and avoidant responses to the past burn trauma. Intrusive-avoidant stress responses could not be predicted by demographic information, severity of the burn, facial disfigurement, or actual responsibility for the burn, but blaming oneself for the injury to the patient was a significant predictor. Evaluating stress responses of close relatives after burn trauma can lead to more successful intervention for those who remain stressed and may enhance patient and family compliance with the treatment and rehabilitation regime. PMID- 3345980 TI - The impact of coexisting depression and timing of psychiatric consultation on medical patients' length of stay. AB - Patients with a psychiatric disorder are known to make greater use of medical resources than patients without a psychiatric condition, but the impact of highly prevalent psychiatric illnesses, such as depression, on use of medical resources has not been fully explored. This study assessed the lengths of stay of 92 medical and surgical patients who met DSM-III criteria for depression and the relationship of their length of stay to the timing of psychiatric consultations. The 92 patients were hospitalized significantly longer (a mean of 2.52 days more) than they would have been had their length of stay been determined by their medical diagnosis-related group (DRG). A subgroup of 38 Medicare patients were hospitalized a mean of 5.22 days more than the mean stay allowed by their DRG. Consultations occurring earlier in the hospitalizations were linked to shorter stays. PMID- 3345981 TI - Time therapy technique: the use of time as a catalyst for treatment. AB - The time therapy technique is a unique approach to group therapy in which the abstract concept of time is represented spatially by a "floor calendar" through which patients move as they discuss past and future events. The technique enables the therapist to assist patients in evaluating the appropriateness of future goals, in increasing their ability to cope with current stressors by reexperiencing positive events, and in resolving past traumatic events through a process of emotional disengagement called disassociative reassurance. Although time therapy technique as yet lacks empirical support, it has been used with adult chronic schizophrenic patients in an ongoing open-ended therapy group, where its effectiveness has been encouraging. PMID- 3345982 TI - Characteristics of state hospital patients who are hard to place. AB - As a result of deinstitutionalization, acute care beds in state hospitals have become blocked by patients who lack access to appropriate community placements but who have derived maximum benefit from hospital care. To help plan community services for these patients, this study identified and described patients at an Oregon state hospital who were hospitalized longer than therapeutically necessary because no community facility could treat them. A total of 146 patients were identified during a three-month period, and 81 were described; 65 percent were men, 70 percent were schizophrenic, and 90 percent presented a risk to themselves or others. The patients exhibited few strengths, and one-third had a substance abuse problem, at least one counter-therapeutic attitude, or a need for medical monitoring. The authors describe how new community residential facilities can meet the needs of these difficult patients. PMID- 3345983 TI - The insanity defense for sex offenders: jury decisions after repeal of Wisconsin's Sex Crimes Law. AB - After repeal of a Wisconsin statute permitting hospitalization of defendants convicted of sexual crimes, the authors noted an increase in the percentage of sex offenders among persons hospitalized after being found not guilty by reason of insanity. They also found that a greater proportion of hospitalized sex offenders than of other kinds of offenders were diagnosed as nonpsychotic. Illustrating with three case studies, the authors argue that despite trends away from the therapeutic model of corrections, juries continue to make decisions that provide treatment for defendants perceived to need it, even if the legal criteria for those decisions do not appear to be met. PMID- 3345984 TI - Treatment, care, and rehabilitation of the chronic mentally ill in Sweden. AB - For the last 20 years in Sweden, there has been a trend to integrate psychiatry with general medical services. However, mental hospitals remain the dominant resource for psychiatric care, with psychiatric units in general hospitals providing less than 20 percent of psychiatric hospital beds. The imbalance between the high number of inpatient facilities and the low rate of outpatient visits is beginning to be corrected by the newly introduced sector system, which allocates mental health care resources among geographic zones. The sector system has been criticized, however, because some believe it is fostering disintegration of existing resources and loss of research opportunities. A general spirit of improvement exists, but at the same time the public budget is being squeezed. PMID- 3345985 TI - Patients' reactions to therapist rotations. PMID- 3345986 TI - Providing culturally sensitive care: intervention by a consultation-liaison team. PMID- 3345987 TI - A misleading diatribe. PMID- 3345988 TI - Risks in physical restraint. PMID- 3345989 TI - Hospitals seek cost cuts in surgery suites. PMID- 3345990 TI - Multis seek alternate care system automation. PMID- 3345991 TI - New drug makes MRI competitive but invasive. PMID- 3345992 TI - Dambro diagnoses clinical information malady. PMID- 3345993 TI - Hospitals probe new and improved financial information systems. PMID- 3345994 TI - "Medical gridlock" and mental health care. PMID- 3345995 TI - Florida malpractice legislation brings hope. PMID- 3345996 TI - Hospital advertising budgets grow by 45%. PMID- 3345997 TI - Managed care marketing crucial. PMID- 3345999 TI - MN health dept. steps into HMO rate dispute. PMID- 3345998 TI - Practice enhancement: what MDs want. PMID- 3346000 TI - As margins fall, executives forge survival tools. PMID- 3346001 TI - Justice dept. outlines merger guidelines. PMID- 3346003 TI - FASB rulings key to retiree health benefits. PMID- 3346002 TI - AHA questions FTC jurisdiction. PMID- 3346004 TI - Retiree issues reaching boil on back burner. PMID- 3346006 TI - Will rise in salaried MDs prompt union growth? PMID- 3346005 TI - Special report: contract management. PMID- 3346007 TI - Managing in hard times: one CEO's turnaround. Interview by Michele L. Robinson. PMID- 3346008 TI - Hemorrhagic endovasculitis-like lesion induced in placental organ culture. AB - In organ culture, human chorionic villi develop vascular changes that resemble so called hemorrhagic endovasculitis. The latter is a morphologic finding more prevalent in placentas of stillborn infants but seen also in those of liveborn infants, in whom the lesion is localized rather than generalized. We compared the histologic vascular changes in short-term organ cultures of 15 placentas (10 term, 5 preterm) with the naturally occurring vascular lesion in 6 placentas (2 liveborn, 4 stillborn). All organ cultures of placentas from liveborn infants developed hemorrhagic endovasculitis-like lesions in the fetal stem arteries; these lesions were present as early as 1 day and persisted for 7 days in culture. A mechanism common to both the in vivo and in vitro systems depending on hypoxia and vascular smooth muscle contraction may explain both the naturally occurring and tissue culture-induced lesions. PMID- 3346009 TI - Mitosis counting in seminoma: an exercise of questionable significance. AB - Two pathologists reviewed and classified 45 cases of testicular seminoma, evaluating each case for multiple histologic variables, including mitotic rate. In addition to recording the mitotic count for each of thirty 0.1963-mm2 high power fields, the investigators recorded the distribution of mitotic counts in many non-spermatocytic seminomas. Statistically significant differences for mitotic rate in the nonspermatocytic tumors were noted between the observers; one observer found a mean mitotic rate of 1.815/high-power field for 43 such tumors, whereas the other noted a mean mitotic rate of 1.388/high-power field (p = 0.001). These differences led to disagreement on the classification of 3 tumors. Of the 4 cases considered to be high-mitotic-rate seminomas by one or both observers, all patients had presented with stage I disease. Three of the patients were followed up for 23, 55, and 56 months, and all were free of disease; the fourth was lost to follow-up. The patient with the highest mitotic rate was free of disease at 55 months of follow-up. On the basis of our findings we question the value of the designation high-mitotic-rate seminoma. Analysis of the distribution of mitotic counts within the tumors revealed them to be Poisson distributed. With these data and other empirically derived data, it was possible to estimate the probability of misclassification of seminoma based on mitotic rate, the diagnostic mitotic rate threshold, and the number of fields counted for mitoses. Similar analysis might be valuable for other tumors, particularly those of smooth muscle origin, in which mitotic rate is of diagnostic or prognostic value. PMID- 3346010 TI - Clinicopathologic studies in childhood pancreatitis. AB - In a review of pediatric autopsies from 1951 to 1985, we identified 40 cases in which pancreatitis was diagnosed pathologically. Twenty-six of these patients were under 4 years of age, and the male-to-female ratio was 1.5. Six groups of patients were identified: 10 with hepatobiliary disease, including 9 with biliary atresia; 7 with immunosuppressive therapy for tumors (n = 2), leukemia (n = 4) and aplastic anemia (n = 1); 6 with viral infections; 8 with congenital anomalies, including congenital heart disease (n = 3); and 9 with miscellaneous problems. Several patients had surgery and various intercurrent complications. Clinical features attributable to the pancreatitis included vomiting or excessive nasogastric drainage (60%), pleural effusions (40%), and abdominal pain (25%). However, the diagnosis was suspected clinically in only 5 of 40 patients. Our findings suggest several pathogenic mechanisms exist for childhood pancreatitis: biliary obstruction, infections, drug toxicity, immunosuppression (acting in synergy with drug toxicity, trauma, and low-flow states resulting from shock, heart failure, and vasculopathy. PMID- 3346011 TI - Human immunodeficiency virus and papovavirus infections in acquired immunodeficiency syndrome: an ultrastructural study of three cases. AB - A wide variety of neurologic conditions associated with the acquired immunodeficiency syndrome (AIDS) have been attributed to human immunodeficiency virus (HIV) infection of the central nervous system (CNS). Tissue samples from the brains of three patients with AIDS, diagnosed as having CNS toxoplasmosis on the basis of computed tomographic scans of the head, were studied by transmission electron microscopy. In two, HIV particles were observed budding from, in close association with, and in cytoplasmic vacuoles of mononuclear and multinucleated macrophages, but no other cell types. The patient with the greatest number of HIV particles also had large amounts of papovavirus (progressive multifocal leukoencephalopathy) in the nuclei of oligodendroglial cells and in the cytoplasm of astrocytes. These astrocytes often had atypical features at the light microscopic level. Following an initial biopsy that showed only HIV, primary CNS lymphoma was diagnosed by needle biopsy and confirmed at autopsy in a second case. A diagnosis of progressive multifocal leukoencephalopathy was rendered by transmission electron microscopy in a third case, but no HIV was detected. Toxoplasmosis was not confirmed in any of the three cases. Diagnosis of CNS lesions in patients with AIDS should not rely exclusively on radiography but include biopsy for both light and transmission electron microscopy. Transmission electron microscopy can be employed to reveal HIV and papovavirus infections not discernible at the light microscopic level and should be used as a diagnostic tool in HIV-related infections. PMID- 3346012 TI - Posterior fossa neuroblastoma occurring in an elderly man. AB - A case of a neuroblastoma occurring in the cerebellum of a 73-year-old man is reported. The patient presented with progressive truncal ataxia and was found to have an enhancing tumor mass in the cerebellar vermis. By light microscopy, the tumor was a small cell neoplasm and was similar to medulloblastoma, with areas showing structures suggestive of Homer-Wright pseudorosettes. By electron microscopy and immunoperoxidase techniques, however, the tumor showed convincing evidence of neuronal differentiation. The absence of previous reports of this tumor in the posterior fossa of adults suggests that immunoperoxidase techniques and/or electron microscopy of such small cell tumors may be required for accurate diagnosis. PMID- 3346013 TI - Tubuloreticular inclusions in colonic mucosa. PMID- 3346014 TI - Turner's syndrome: a qualitative and quantitative analysis of EEG background activity. AB - A qualitative and quantitative analysis was performed on the EEG background activity in 62 Danish girls and women with Turner's syndrome (30 with karyotype 45,X and 32 with other karyotypes) whose ages ranged from 6 to 47 years (87% were aged 15 years or more) and age-matched controls. The pooled data and a case control study showed characteristic features in Turner subjects, including: (1) more rapid frequency, larger amplitude and lower amount of alpha waves, (2) higher amount of theta waves, (3) larger amplitude and higher amount of delta waves and (4) larger amplitude and higher amount of beta waves than in controls. These findings in Turner subjects were more pronounced in the left hemisphere, and more typical, except for the amplitude in alpha waves, in Turner subjects with 45,X than in those with other karyotypes. The effects of advancing age on the EEG background activity observed in controls--including more rapid frequency, decreased amplitude and amount of alpha waves, increased amount of theta and delta waves, and increased amount of beta waves, particularly after 35 years of age--were found in some Turner subjects. Hemispheric differences with higher activity (i.e. more rapid frequency, larger amplitude and higher amount of alpha waves, particularly at Fp1 and F3, and, inversely, lower amount of theta or delta waves) at P3, T3, T5 and O2 than at the opposite side were found in many Turner subjects. However, these findings were not specific for Turner subjects, since the same hemispheric differences were also observed much more markedly in controls. These topographic distributions with hemispheric differences did not provide evidence for hypofunction in the temporo-parieto-occipital tertiary area of the right hemisphere in Turner subjects, though this had been expected on the basis of neuropsychological examinations. Our findings, including transiently appearing brain hypofunction at the parietal, temporal and occipital areas, most often in the right hemisphere, indicate a relationship between the chromosomal constitution 45,X and EEG background activity. They suggest the presence of functional brain disturbance in the thalamus and in the ascending reticular activating system, which tends to disturb the thalamo-cortical circuit. Further studies, including topographic and sequential power spectrum analysis of EEG background activity, 24-h continuous EEG recording, blood flow studies (positron computerized tomography) and neuropathological examination, may be needed. PMID- 3346015 TI - The possible role of meiotic pairing anomalies in the atresia of human fetal oocytes. AB - Following a previous study of human fetal oocytes analysed by light and electron microscope microspreading (Speed 1985), a further and more extensive analysis has now been carried out at electron microscope (EM) level. Some new anomalies not previously observed are described. More than one-third of all pachytene oocytes show degeneration (Z-cells) or synaptic errors which might lead to germ cell death. Meiotic pairing anomalies appear to be much more common among oocytes than spermatocytes, and could be significant factor in the high rate of atresia found between mid-term and birth in the human ovary. PMID- 3346016 TI - Prenatal diagnosis of cystic fibrosis by microvillar enzyme assay on a sequence of 258 pregnancies. AB - Prenatal diagnosis of cystic fibrosis by microvillar enzyme assay on amniotic fluid supernatant has been carried out on 258 sequential pregnancies with a 1 in 4 recurrence risk, all with known outcome. In general the three enzymes evaluated, gamma-glutamyltranspeptidase, aminopeptidase M and the intestinal isoenzyme of alkaline phosphatase, showed a high degree of concordance. However, there were two unusual patterns of microvillar enzyme activity; in seven cases a low gamma-glutamyltranspeptidase activity was associated with elevated values of intestinal alkaline phosphatase, and in ten cases there were isolated low values of intestinal alkaline phosphatase. The former pattern was found to be associated with cystic fibrosis in five cases, while the latter was associated with a normal outcome in all ten cases. A retrospective analysis of enzyme values suggested that the optimal system for minimizing false positives and false negatives was to define foetal cystic fibrosis as a sample where two of the three microvillar enzymes were below a cut-off of half the median value for the gestational week. If such scoring were applied to the cases where conventional microvillar enzyme patterns were observed, the false positive rate was 2.3% and the false negative rate 4.4% between 17 and 20 weeks of gestation. PMID- 3346017 TI - Germinal mosaicism in Duchenne muscular dystrophy. AB - We have identified a Duchenne muscular dystrophy (DMD) pedigree where the disease is associated with a molecular deletion within the DMD locus. We have examined the meiotic segregation products of the common female ancestor using marker restriction fragment length polymorphisms (RFLPs) detected by probes that lie within this deletion. These studies show that this female has transmitted three distinct types of X chromosome to her offspring. This observation may be explained by postulating that the mutation arose as a postzygotic deletion within this common ancestor, who was consequently germinally mosaic. PMID- 3346018 TI - Nebulin seen in DMD males including one patient with a large DNA deletion encompassing the DMD gene. AB - The presence of nebulin in a muscle specimen from a patient with Duchenne muscular dystrophy (DMD) due to a large deletion precludes the possibility that this protein is the DMD gene product. PMID- 3346020 TI - Concurrence of the triple-X syndrome and expression of the fragile site Xq27.3. AB - The Xq27.3 fragile site was found to be expressed in an XXX woman, who was mentally and physically normal, and in her son who was mentally retarded and showed behavioural and physical features characteristic of the fragile X syndrome. PMID- 3346019 TI - A "new" allele of esterase D in a retinoblastoma family. AB - We describe a new rare allele for esterase D (EsD) occurring in a Portuguese family with retinoblastoma in two generations. PMID- 3346021 TI - A report of four different unusual 6-PGD electrotypes in Caucasian and Negro populations. AB - Four different unusual 6-phosphogluconate dehydrogenase (6-PGD) electrophoretic patterns found among the Italian (Rome), Bamileke (Cameroon), and North Bateke and Babenga Pygmy (Congo) populations are described. PMID- 3346022 TI - Role of sexually transmitted diseases in transmitting human immunodeficiency virus. PMID- 3346024 TI - Sexual behaviour in women attending a genitourinary medicine clinic. AB - In 1025 women attending a genitourinary medicine (GUM) clinic, sexual experience had started at an increasingly early age during the past 30 years, from a mode of 19 in the early 1950s to 16 in the early 1980s. Up to the age of 40, sexually active older women had as many recent sexual partners as younger women. Oral intercourse (fellatio) was practised by 714 (70%) women, and 378 (37%) experienced ejaculation in the mouth. Anal intercourse was practised by 200 (20%) women and 90 (9%) experienced ejaculation in the anorectum. The prevalence of all these practices increased with age. Women attending a Family Planning Association (FPA) clinic reported a similar prevalence of these practices, and differed from GUM clinic women only in the number of sexual partners in the preceding year. In the GUM group, black women reported significantly fewer recent sexual partners than did white women, and significantly fewer black women practised oral intercourse or permitted anal penetration. Full anal intercourse with ejaculation into the anorectum was practised at least occasionally by 9% (80/873) of white and 8% (10/131) of black women. PMID- 3346023 TI - Influence of gender in pathogenesis of trichomoniasis in congenitally athymic (nude) mice. AB - Evaluation of abscesses appearing in male and female euthymic and athymic (nude) Balb/c mice after subcutaneous injection of Trichomonas vaginalis in the dorsal region showed that females were more susceptible than males. Female euthymic mice, however, were more susceptible than male athymic mice, and splenectomised athymic males were more susceptible than non-splenectomised athymic males. F1 female athymic mice were the most susceptible, as their abscesses reached a peak size five days earlier than those of athymic homozygous females. F1 male athymic mice, though slightly more susceptible than athymic homozygous males, did not develop abscesses that were similar in size. These results suggest that resistance or susceptibility to T vaginalis infection depends on the gender of the host and on thymus dependent cellular populations. PMID- 3346028 TI - Decrease in incidence of women treated in hospital for acute salpingitis in Sweden. AB - Numbers of women discharged from hospital after being treated for acute salpingitis decreased by 40% in Sweden between 1974 and 1984. Several factors argue that this decrease was real, rather than a shift from inpatient to outpatient treatment. (Outpatients here include those treated by general practitioners as well as at hospital outpatient clinics). The decrease was nation wide and included all age groups. Repeat episodes of the disease decreased more than first episodes. The main reason for the decrease seems to be more strict attitudes to sexual relationships, especially in young people. Public and professional awareness of genital chlamydial infections was probably a contributing factor. PMID- 3346027 TI - Sexually transmitted diseases in a British military force in peacetime Europe, 1970-83. AB - A retrospective analysis was performed to identify the incidence and pattern of sexually transmitted diseases (STD) affecting a modern British peacetime military force in 1970-83. Relative risk factors for a comparable UK civilian population were assessed and showed a slightly greater risk or the military only in 1974-81. The development of incidence and pattern of STD affecting the military force was shown to be broadly similar to trends in the UK. PMID- 3346025 TI - Prevalence, incidence, and risk of acquiring urogenital gonococcal or chlamydial infection in prostitutes working in brothels. AB - At two week intervals specimens were taken from 24 prostitutes working in two brothels and cultured for urogenital infection with Chlamydia trachomatis and Neisseria gonorrhoeae. Demographic and clinical data were also collected. C trachomatis was found initially in four and N gonorrhoeae in two of the 20 women at risk of infection. During the study period three new chlamydial and gonococcal infections were diagnosed, resulting from 949 unprotected contacts. Eight women (33%) had developed salpingitis, in contrast to 15% in the general female population. An attempt was made to estimate the infectivity of C trachomatis for the prostitutes. The epidemiological importance of the chlamydial and gonococcal reservoir in the prostitutes was also considered. PMID- 3346026 TI - Prophylaxis against infection in Singaporean prostitutes. AB - One hundred prostitutes were interviewed about the prophylactic measures they took against infection. The use of contraceptive diaphragms and clandestine antibiotics correlated significantly with fewer gonococcal infections. PMID- 3346029 TI - Oropharyngeal carriage of Neisseria gonorrhoeae and its response to treatment in patients with anogenital infection. PMID- 3346031 TI - Monogamy is... PMID- 3346030 TI - Rotavirus diarrhoea in patient with antibody to human immunodeficiency virus (HIV) PMID- 3346032 TI - Chancroid in Liverpool. PMID- 3346033 TI - Penicillin treatment for gonorrhoea in relation to early syphilis in prostitutes. AB - A retrospective study of prostitutes in Singapore showed that they had received less antigonorrhoeal treatment with penicillin derivatives during the three month period before early syphilis was diagnosed than in other three month periods when they had not developed syphilis. This suggests that penicillin derivatives in doses sufficient to treat gonorrhoea will abort coincidental early syphilis. PMID- 3346034 TI - Effects of extended feeding of decocainized erythroxylon coca leaves on growth and selected organs in rats and rabbits. AB - Erythroxylon coca leaves from the Trujillo area of Peru were extracted with methylene chloride to remove most cocaine-like alkaloids. The decocainized leaves were formulated in a honey-water vehicle and fed on a chronic basis to female rats for 32 weeks and female rabbits for 13 weeks. Rabbits fed decocainized leaves at doses of 21 or 210 mg demonstrated no significant change in growth (weight gain) when compared with those receiving vehicle. Histological findings were unremarkable except for fatty islands in the myocardium. Rats fed the decocainized leaves at doses of 1.5 and 15 mg demonstrated no significant changes in weight, whereas those receiving 150 mg had a significant decrease in weight gain when compared with control animals receiving vehicle. Necropsy findings in rats demonstrated pyometra in all groups receiving decocainized leaves as well as in some of the controls. Those rats with pyometra often exhibited endometrial metaplasia. Renal tubular calcification and proteinaceous material were consistently noted at all dose levels. Portal triaditis was also found in the livers of most rats. PMID- 3346035 TI - Cigarette and nicotine chewing gum toxicity in children. AB - A prospective review of 51 cases of tobacco ingestion and 5 cases of nicotine resin chewing gum exposure was conducted to evaluate the incidence and degree of toxicity caused by these products in children. A dose-response relationship was observed for cigarette exposures. Nine of 10 children ingesting more than one cigarette or three cigarette butts developed signs or symptoms, while 12 of 24 ingesting lesser amounts became symptomatic (P less than 0.01). Severe symptoms (e.g. limb jerking and unresponsiveness) were only seen with the larger amounts. Nicotine resin gum produced toxicity in 4 of 5 children who chewed 1/2 to 4 pieces. Agitation, lethargy, tachycardia, hypotension, abdominal pain, and vomiting were seen within 30 min of exposure to the gum. PMID- 3346036 TI - More about spontaneous reports of suspected adverse drug reactions. PMID- 3346037 TI - Fatal paracetamol poisoning in an epileptic. AB - Treatment nomograms are used in paracetamol poisoning for indicating when antidotes should be given to prevent hepatic or renal damage. We report a fatal case of paracetamol poisoning in an epileptic taking phenytoin, in whom no antidotal treatment was given because it was not indicated. PMID- 3346039 TI - Hypernatraemia and hyperchloraemic acidosis after bleach ingestion. AB - The deliberate ingestion of household 'strong' bleach (NaOCl) caused severe metabolic disturbance. Hyperchloraemic acidosis was probably due to NaOCl reacting with hydrochloric acid in the stomach to form hypochlorous acid and chlorine. 'Strong' household bleach contains 10% NaOCl and this provides a large sodium load. The ingestion of 500 ml contained 673 mmol sodium and caused hypernatraemia. PMID- 3346038 TI - Pulmonary infiltration and lymphadenopathy in association with fenbufen. PMID- 3346040 TI - Proceedings of the second joint meeting of the Nederlandse Vereniging voor Toxicologie and the British Toxicology Society. Leyden, The Netherlands, 17-19 May, 1987. Abstracts. PMID- 3346041 TI - T-cell receptor gene rearrangement and expression in human natural killer cells: natural killer activity is not dependent on the rearrangement and expression of T cell receptor alpha, beta, or gamma genes. AB - To test the hypothesis that the T-cell receptor (Tcr) gamma gene encodes a natural killer (NK) cell receptor molecule, three human NK clones and fresh peripheral blood lymphocytes with NK activity from two patients with a CD16+ lymphocytosis were analyzed for rearrangements and expression of the human Tcr alpha, beta, and gamma genes. Two of the clones displayed distinct rearrangements of their Tcr beta and gamma genes and expressed mature Tcr alpha, beta, and gamma RNA. However, one of the clones and both patient samples displayed marked NK activity but failed to rearrange or express any of their Tcr genes. These findings demonstrate that human natural killer activity is not dependent on Tcr gamma gene rearrangement and expression. In addition, they confirm previous findings concerning the lack of Tcr alpha and beta gene expression in some natural killer cells. Thus, they suggest the existence of additional NK-specific recognition molecules. PMID- 3346042 TI - Genetic basis of ultraviolet-B effects on contact hypersensitivity. AB - The genetic basis of the effects of ultraviolet B (UVB) radiation on the induction of contact hypersensitivity (CH) to dinitrofluorobenzene (DNFB) has been explored in genetically defined mice. It was found that acute, low-dose UVB radiation produced profound depletion of epidermal Langerhans cells (LC) at UVB treated sites in all strains of mice tested. However, when DNFB was applied to UVB radiation sites, unresponsiveness developed in some strains of mice, but vigorous contact hypersensitivity was induced in others. The UVB-susceptible phenotype proved dominant or codominant in F1 hybrids derived from parental strains of the susceptible and UVB-resistant phenotypes. Experiments conducted in one set of F1 hybrids derived from two UVB-susceptible parental strains displayed UVB resistance, suggesting gene complementation, and showed that more than one genetic locus was involved. Segregant backcross populations, analyzed for the capacity to develop CH after UVB treatment and skin painting with DNFB, revealed that at least two, and probably three, independent genetic loci participate in determining UVB resistance. Results of experiments with H-2 congenic and recombinant mice derived from the B10 background implicated class I genes of the major histocompatibility complex as relevant genetic factors. These results indicate that there is a dissociation between the effects of UVB radiation on epidermal Langerhans cells and the capacity of a cutaneous surface to support the induction of contact hypersensitivity. The data indicate that the induction of CH to haptens is dependent on normal numbers of functional LC at the skin painting site only in some strains of mice. The data imply that in the so-called UVB resistant strains of mice, alternative (non-Langerhans cell-dependent) mechanisms allow for the induction of CH. Several independent genetic loci, one of which appears to be H-2, govern this UVB-related effect. PMID- 3346043 TI - Mouse immunoglobulin allotypes: multiple differences between the nucleic acid sequences of the IgEa and IgEb alleles. AB - To clarify the allotypic difference of the IgE antibody molecule, we determined the complete nucleotide sequence of the genes encoding the constant portion of mouse IgE of a (BALB/c) as well as b (B10.A) allotypes. A comparison of the sequences revealed that there were 12 single-base changes: 2 single-base changes in CH1 and CH2, 3 in CH3, and 7 in CH4. Five of them were silent changes, but seven resulted in amino acid substitutions. Although the silent changes are scattered through CH1 to CH4, the nonsilent substitutions were found only in CH3 (two substitutions) and CH4 (five). The allotypic determinant(s) that conventional antisera detect most likely reflects an amino acid difference(s) in CH3 and/or CH4. PMID- 3346045 TI - Proceedings of the seventh scientific meeting of the Inter-American Society of Hypertension, 1987. Buenos Aires, May 10-13, 1987. PMID- 3346044 TI - A new mouse lymphocyte alloantigen (Ly-35) controlled by the Ly-2/3 region on chromosome 6. PMID- 3346046 TI - Extent of baroreceptor resetting in response to sodium nitroprusside and verapamil. AB - We investigated the effect of sodium nitroprusside, verapamil, and hemorrhage on the resetting of the aortic baroreceptors of normotensive control rats to hypotension, and the reversal of resetting of baroreceptors of one-kidney, one clip hypertensive rats to normotension. Using whole-nerve recording, the extent (%) of resetting (or reversal of resetting) observed 15 minutes after a maintained fall in mean arterial pressure (MAP) was evaluated by the ratio between changes of systolic threshold pressure for baroreceptor activation and changes of control diastolic pressure exhibited by the rats, multiplied by 100. Three groups of normotensive control rats showed a MAP decrease to hypotensive levels of 33%, 39%, and 41%, respectively, with sodium nitroprusside, verapamil, and hemorrhage. The corresponding extent of resetting was 96 +/- 3%, 39 +/- 2%, and 46 +/- 4%, respectively. Only in the group treated with verapamil did MAP and systolic threshold pressure not revert completely to normotensive levels 15 minutes after the end of drug infusion. Three groups of one-kidney, one clip hypertensive rats showed MAP normalization of 30%, 37%, and 31%, respectively, with sodium nitroprusside, verapamil, and hemorrhage. The corresponding extent of reversal of resetting to normotension was 107 +/- 3%, 40 +/- 2%, and 60 +/- 9%, respectively. Again, only in the group treated with verapamil did MAP and systolic threshold pressure not revert to hypertensive levels 15 minutes after infusion. Besides indicating that different vasodilators can differently modulate the rapid (15-minute) resetting (or reversal of the resetting) due to similarly maintained fall in MAP, these data suggest that verapamil has a nonspecific effect on the baroreceptors, whereas sodium nitroprusside appears to affect baroreceptor transduction. PMID- 3346047 TI - The central pressor effect of bradykinin in normotensive and hypertensive rats. AB - The site of action for the pressor response to bradykinin administered into the lateral ventricle has been reported to be either in the septal area or in the ventral portion of the third ventricle. We obtained dose-response curves for the pressor effect of bradykinin injected into the lateral ventricle or the posterior region of the fourth ventricle of normotensive Wistar and spontaneously hypertensive rats (SHR). Responses to fourth ventricle injections had a shorter latency and larger maximal effect, and were 20 to 100 times greater than those to lateral ventricle injections, suggesting that the site of bradykinin's action is in the caudal region of the brain, probably close to the area postrema. Maximal effects were similar for lateral and fourth ventricle injections in both SHR and normotensive rats, but SHR were much more sensitive to bradykinin. The ED50 values for the lateral ventricle route in normotensive rats and SHR were 1.3 and 0.35 nmol, respectively, and, for the fourth ventricle route, 60 and 3.4 pmol, respectively. Responses to Lys-Lys-bradykinin, a kininase-resistant bradykinin analogue, showed that kininase activity is lower in SHR than in normotensive rats and that SHR are four times more sensitive to Lys-Lys-bradykinin than are normotensive rats. The responses of all rats were inhibited by a specific bradykinin receptor blocker [Thi5,8,DPhe7]bradykinin. Our results show that there is a site of bradykinin action that is far more caudal than those previously described. The shorter latency and higher sensitivity of the fourth ventricle injection suggest that bradykinin injected into the lateral ventricle diffuses to the fourth ventricle where it exerts its effects. PMID- 3346048 TI - Increased DNA replication in the arterial adventitia after aortic ligation. AB - After microsurgical dissection of the thoracic aorta of normotensive rats, biochemical and morphological comparisons were performed between the intima-media and adventitia. The DNA content, wet weight, and dry defatted weight of the adventitia were half that of the intima-media. Collagen was the main component of the adventitia (collagen greater than nonfibrous protein greater than elastin) whereas elastin was the main protein in the intima-media (elastin greater than nonfibrous protein greater than collagen), and the results correlated with morphological observations. Hypertension induced by aortic ligation between the renal arteries resulted in rapid elevations in circulating humoral factors and blood pressure. A sixfold increase in DNA synthesis was observed in the adventitia (p less than 0.001), resulting in a significant increase in DNA content as early as 6 days after aortic ligation (75% increase; p less than 0.001). Increased DNA replication was accompanied by elevations in nonfibrous protein and elastin contents. Autoradiograms showed labeled adventitial fibroblasts throughout the thickness of the adventitia and along the entire length of the aorta and smaller vessels. DNA synthesis and content and labeled smooth muscle cells were increased in the intima-media. These studies indicate that the adventitia participates in the development of vascular hypertrophy and arterial disease produced by aortic ligation. PMID- 3346049 TI - Effect of nucleus ambiguus lesion on the development of neurogenic hypertension. AB - These studies evaluated the role of the nucleus ambiguus in regulating heart rate and cardiovascular activity. Three days after lesion of the nucleus ambiguus, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of pressure (156 +/- 4 vs 124 +/- 6 mm Hg) compared to sham lesion. In both groups the heart rate was increased after deafferentation and the intrinsic heart rate (rate seen after autonomic blockade with atropine and propranolol) was significantly reduced. When the sequence was reversed (deafferentation before lesion), pressure (126 +/- 6 vs 126 +/- 7 mm Hg) and heart rate (334 +/- 17 and 340 +/- 16 beats/min) were not altered; however, intrinsic rate fell more. When the nucleus ambiguus was stimulated electrically, two responses emerged: increased pressure without rate changes and increased pressure with bradycardia. These data indicate that 1) lesion of the nucleus ambiguus facilitates hypertension produced by sinoaortic deafferentation unless lesioning follows deafferentation; and 2) stimulation of the nucleus ambiguus produces a pressor effect that is independent of the bradycardic response. We conclude that the nucleus ambiguus may be related to autonomic control of both heart rate and arterial pressure. PMID- 3346050 TI - In vivo release of angiotensin II from the rat hypothalamus. AB - Recent studies suggest that angiotensin II is released from neuronal tissue in vitro, but the occurrence of this phenomenon in the intact brain has not yet been demonstrated. To characterize the in vivo release of immunoreactive angiotensin II, push-pull cannulas were positioned in the anterior hypothalamus in 47 Sprague Dawley rats (200-250 g) anesthetized with Inactin (100 mg/kg i.p.). Artificial cerebrospinal fluid was perfused at 20 microliters/min, and effluent samples were collected for 15-minute periods over 2 hours. Angiotensin II was detectable (greater than 2.5 pg/ml) in the push-pull cannula perfusate of the majority (76%) of the rats. Spontaneous release of immunoreactive angiotensin II was constant for 2 hours in 11 rats at values averaging from 4.4 +/- 1.5 to 8.2 +/- 2.2 pg/ml. In addition, bilateral nephrectomy performed 48 hours before did not affect the detection of angiotensin II (n = 3). Angiotensin immunoreactivity in the rat hypothalamus was further characterized by high performance liquid chromatography. The analysis showed that the perfusate contained authentic angiotensin II as well as other angiotensin metabolites. The effect of beta-adrenergic modulation on the release of angiotensin II was assessed in 20 rats by adding isoproterenol (10( 10), 10(-8), and 10(-6) M), propranolol (10(-6) M), or a combination of both. Neither activation nor inhibition of hypothalamic beta-receptors altered the spontaneous release of angiotensin II. These data demonstrate that angiotensin II and congener peptides are detectable in the microenvironment of the anterior hypothalamus of the anesthetized rat and that the release of angiotensin II immunoreactivity in the anterior hypothalamus is not modified by beta-adrenergic receptors. PMID- 3346051 TI - Baroreceptor reflex modulation by angiotensin II at the nucleus tractus solitarii. AB - This study characterized the effect of nucleus tractus solitarii (NTS) microinjection of the angiotensin II (Ang II) antagonist [Sar1, Thr8]Ang II on the baroreceptor control of heart rate in anesthetized rats. Reflex changes in heart rate were elicited by bolus intravenous injections of either phenylephrine or sodium nitroprusside before and after bilateral microinjection of [Sar1, Thr8]Ang II (100 pmol) or vehicle into the NTS. The slope of the relationship between the change in pulse interval and the change in mean arterial pressure was used as an index of baroreceptor reflex sensitivity. Bradycardia elicited by phenylephrine-induced increases in pressure was significantly greater after NTS injection of [Sar1, Thr8]Ang II. The slope of the pulse interval-arterial pressure relationship was 0.60 +/- 0.09 ms/mm Hg after injection, as compared with 0.42 +/- 0.07 ms/mm Hg before. In contrast, the baroreceptor reflex sensitivity index generated by decreases in pressure with nitroprusside was similar before and after injection. Vehicle injections did not alter the baroreceptor reflex index. Collectively, the data suggest that inhibition of endogenous Ang II in the NTS facilitates the baroreceptor reflex sensitivity to increases, but not decreases, in pressure. This new finding reveals the NTS as one site of action for the tonic effects of endogenous Ang II. PMID- 3346052 TI - Characteristics of hormonal and neurogenic mechanisms of deoxycorticosterone induced hypertension. AB - We characterized the hemodynamic and endocrine changes associated with the evolution of steroid-induced hypertension in conscious, trained, instrumented dogs given intramuscular injections of deoxycorticosterone (DOC) pivalate on Days 1 (20 mg/kg) and 14 (10 mg/kg) of the study. Because hypertension could be produced in these dogs without salt loading and unilateral nephrectomy, the research afforded a novel opportunity to determine the primary effects of DOC excess on the renin-angiotensin and sympathetic nervous systems, and on vasopressin levels. Both before and during 28 days of DOC treatment, regular measurements of mean arterial pressure, heart rate, cardiac output, and total peripheral resistance were coupled with serial determinations of plasma and cerebrospinal fluid levels of angiotensin II, vasopressin, norepinephrine, and electrolytes. DOC induced a progressive rise in mean arterial pressure associated with increased cardiac output and no change in heart rate. These hemodynamic changes were accompanied by sustained decreases in plasma renin activity, and in plasma, but not cerebrospinal fluid, angiotensin II. In contrast, plasma and cerebrospinal fluid vasopressin rose transiently on the 7th and 14th days of the study, respectively. After anesthesia with morphine and chloralose, the hemodynamic response to occlusion of a sole innervated carotid artery was evaluated on the 5th week before and after cervical vagotomy. Compared to normal animals, dogs with DOC-induced hypertension showed a reduced pressor response to carotid occlusion associated with suppression of reflex tachycardia; vagotomy partially restored the pressor response to normal levels. The data suggest that DOC-induced hypertension changes central hormonal influences of cardiovascular function, and also alters cardiopulmonary baroreceptor reflex control of peripheral sympathetic nerve activity. PMID- 3346053 TI - Influence of the anteroventral third ventricle region and sinoaortic denervation on the pressor response to carotid occlusion. AB - The effect of anteroventral third ventricle (AV3V) lesion on the pressor response to occlusion of the common carotid artery was studied in freely moving rats with cuffs implanted 1 day before the tests. Short-term (6 hours) and long-term (2, 14, and 30 days) lesions greatly depressed the pressor responses to 60 seconds of common carotid occlusion. The initial peak, which depends on carotid innervation, was reduced by 55% (from 42 +/- 2 to 20 +/- 2 mm Hg), and the maintained response, which is of central origin (probably ischemic), was reduced by 32% (from 31 +/- 2 to 21 +/- 2 mm Hg). The effect of carotid or aortic denervation (or both) was also studied on control and lesioned rats. Carotid denervation produced similar extent of depression of the normal and reduced responses of the AV3V-lesioned rats 35% and 37%, respectively. Aortic denervation produced similar relative potentiation of the responses to common carotid occlusion of control and lesioned rats (72% and 66%, respectively). These data indicate the following: 1) Both short-term and long-term lesions greatly reduce the reflex and central (ischemic) components of the pressor responses to common carotid occlusion in freely moving rats; and 2) the importance of carotid innervation for development of the initial peak and the marked inhibitory effect of the aortic baroreceptor on both components are unchanged after AV3V lesion, when the depressed responses are evaluated as percent changes of the control values rather than as absolute changes. PMID- 3346054 TI - Hypotensive spinal serotonergic effect. Are S1 or S2 receptors involved? AB - Since previous data obtained in anesthetized rats supported the idea that the activation of spinal serotonergic receptors induced a hypotensive effect, it was decided to characterize more closely the serotonergic spinal involvement and to elucidate the serotonergic receptor type involved in this effect. After female Wistar rats were anesthetized, the femoral artery (for blood pressure measurement) and vein (for parenteral injection of drugs) were cannulated. An intrathecal catheter was positioned with the tip at the T6-L3 intervertebral space. The results showed that the dose-dependent decrease in mean blood pressure induced by serotonin administered at the T6-L3 level was prevented by giving the serotonergic S2 antagonist ritanserin intravenously. The intravenous administration of 5-methoxy-N,N-dimethyltryptamine, a direct serotonergic agonist, induced a dose-dependent hypotension previously shown to originate at spinal cord level. This effect was prevented by intrathecal administration of ketanserin, an S2-receptor antagonist. The selective agonist of the S1-type receptors, 8-hydroxy-dipropylaminotetralin, given at the same level of the spinal cord, failed to induce any effect on mean blood pressure. The results suggest that the hypotensive effect obtained after the spinal serotonergic activation involves serotonin receptors of the S2 type. PMID- 3346055 TI - Tidal volume affects the response to inactivation of the rostral ventrolateral medulla. AB - During preliminary studies of the rostral ventrolateral medulla as a relay site for responses activated from forebrain, loss of the marked depressor effect of lidocaine, microinjected into lateral rostral ventrolateral medulla, was observed when rats were ventilated spontaneously rather than by artificial ventilation. The mechanism of this effect was studied in rats ventilated at a tidal volume of 2.5 ml. Bilateral injection of 4% lidocaine into lateral rostral ventrolateral medulla decreased mean arterial pressure by -47 +/- 8 mm Hg and heart rate by -68 +/- 21 beats/min. Reduction of tidal volume to 1.5 ml significantly attenuated the fall in mean arterial pressure and heart rate produced by lidocaine to -17 +/ 11 mm Hg and -12 +/- 8 beats/min. The decrease in tidal volume resulted in decreased arterial PO2 and pH, and increased PCO2. However, the depressor effect of lidocaine was not significantly affected by independently changing PO2 and PCO2. The physical stimuli associated with reduction of tidal volume (i.e., changes in lung inflation and chest wall movement) appeared to mediate the attenuated depressor response to the injection of lidocaine into the lateral rostral ventrolateral medulla. These data suggest that 1) tonic vasomotor activity derived from lateral rostral ventrolateral medulla is strongly influenced by altered mechanics of respiration, and 2) the anatomical location of the putative vasomotor center may not be defined by the lateral rostral ventrolateral medulla under all conditions. PMID- 3346056 TI - Effect of central serotonin depletion on blood pressure and the renin system in rats. AB - In the present study we examined the effect of depletion of central nervous system serotonin by 5,7-dihydroxytryptamine on blood pressure in male Wistar rats. We also analyzed the relationship between the serotonergic and renin angiotensin systems. Blood pressure was determined before and after intracisternal administration of 5,7-dihydroxytryptamine, 200 micrograms in saline with 1 mg/ml ascorbic acid (n = 9). Control rats (n = 8) received intracisternal vehicle. Before sacrifice, blood and cerebrospinal fluid samples were obtained. The brain was dissected in several areas. Serotonin, norepinephrine, angiotensinogen, and reninlike concentrations were determined in the brain parenchyma; angiotensinogen concentration was evaluated in cerebrospinal fluid and plasma samples; plasma renin activity was also measured. Treatment produced a significant decrease in blood pressure (-10 mm Hg; p less than 0.025) and, simultaneously, a high depletion of serotonin stores in the studied central areas (p less than 0.001), except in the cerebral cortex. Reninlike concentration was increased in the medulla oblongata (p less than 0.005) and the brainstem (p less than 0.02) after 5,7-dihydroxytryptamine treatment. Angiotensinogen concentration was decreased in the hypothalamus and elevated in the spinal cord. Angiotensinogen concentration in cerebrospinal fluid, plasma angiotensinogen concentration, and plasma renin activity did not change with treatment. Serotonin concentration in the cerebrospinal fluid remained unchanged, while the 5-hydroxyindoleacetic acid level was diminished ( 47%; p less than 0.001). Intracisternal administration of 5,7-dihydroxytryptamine produced a hypotensive effect in normal rats and several modifications of the renin-angiotensin complex, suggesting a relationship between the monoaminergic and peptidergic systems. PMID- 3346057 TI - The effect of a community hypertension control program. AB - A hypertension detection and control program sponsored by the Pan-American Health Organization and the World Health Organization (PAHO/WHO) was carried out in an urban health district of Havana City, Cuba. A baseline (initial) survey was conducted on a random sample of the population (greater than or equal to 15 years of age) to assess the problem of hypertension in that community. Subsequently, we extended the program in the same area by taking the blood pressure of as many people as we could, and a health education program on hypertension was developed and implemented. All hypertensive persons were treated. We surveyed about 90% of the adult population (29,640) over a 5-year period. We then conducted a final survey on a second random sample of the population to assess the effect of the program. The response rate to the letter of invitation to visit the hypertension clinic was 50%; 30% of the recall appointments were missed, and the dropout rate was 18.6%. Seventy percent of the hypertensive persons had Stage I disease (PAHO/WHO) with normal electrocardiograms. Before the program, 15.7% of the total number of hypertensive persons surveyed in the area had the disease under good control, and this increased to 31% after the program. Mortality due to cerebrovascular disease was reduced from 11/10,000/yr to 7/10,000/yr, whereas mortality caused by myocardial infarction did not change. PMID- 3346058 TI - Total plasma dopamine/norepinephrine ratio in catecholamine-secreting tumors. Its relation to hypertension. AB - We used a radioenzymatic method to determine plasma levels of free and total (free plus sulfoconjugated) norepinephrine and dopamine in 20 children with neuroblastoma (two were hypertensive), seven patients with pheochromocytoma, and 39 normotensive controls (24 children and 15 adults). No significant differences were noted between the two control groups. Patients with neuroblastoma and pheochromocytoma showed significantly higher levels of free and total norepinephrine than controls (p less than 0.01), and those with pheochromocytoma had higher levels than those with neuroblastoma (p less than 0.01). Although the differences were not statistically significant, free dopamine was higher in both groups of patients than in controls. Total dopamine was significantly higher in patients than in controls (p less than 0.01). A positive correlation was noted between levels of total norepinephrine and total dopamine in controls (r = 0.41, p less than 0.05) and in patients with neuroblastoma (r = 0.72, p less than 0.001). Such a correlation was not found in patients with pheochromocytoma. The total dopamine/total norepinephrine ratio was higher (p less than 0.005) in patients with neuroblastoma than in controls and patients with pheochromocytoma. Patients with pheochromocytoma had significantly lower ratios than the other groups (p less than 0.001). A negative correlation was found between the ratios in the different groups and either systolic (p less than 0.001) or diastolic (p less than 0.001) blood pressure. Our results not only support a role for plasma dopamine in the regulation of blood pressure but also suggest that, regardless of the actual levels of both catecholamines, a balance has to be achieved in order to maintain normal blood pressure levels. PMID- 3346059 TI - Clinical implications of primary aldosteronism with resistant hypertension. AB - Twenty-eight patients with resistant hypertension were found to have primary aldosteronism; 25 had solitary adenoma and 3 had adrenal hyperplasia. All were severely hypertensive despite receiving three or more antihypertensive agents, including conventional doses of diuretics, sympatholytics, and vasodilators. Hypervolemia (24 patients) or normovolemia (2 patients) despite severe diastolic hypertension was the hallmark in 26 patients. Adequate salt and water depletion alone with spironolactone (200 mg/day) and hydrochlorothiazide (50-100 ng/day) reduced arterial pressure in all. Twenty-two patients had surgical removal of a solitary adenoma. Over 1 to 2 years of follow-up, 13 were normotensive without medication, and six required hydrochlorothiazide and three hydrochlorothiazide plus a beta-blocker to normalize blood pressure. Blood pressure response to surgery had no relation to either duration or severity of hypertension. Six patients (three with hyperplasia, three with adenoma) have continued diuretic therapy and are normokalemic and normotensive. These results indicate that primary aldosteronism can be associated with sever and drug-resistant hypertension, that maintained hypervolemia is the reason for resistance to therapy, that sustained volume depletion is the most important therapeutic goal for these patients, and that cure can be achieved despite prolonged and severe hypertension. PMID- 3346061 TI - Hypertension in Latin America. Special Report. PMID- 3346060 TI - The role of vasopressin in blood pressure maintenance in diabetic orthostatic hypotension. AB - The purpose of these studies was to assess the role of vasopressin in maintaining supine and upright blood pressures in hypertensive diabetic subjects. Patients with (n = 6) or without (n = 10) evidence of autonomic insufficiency had blood pressure and heart rate monitored before and after receiving an intravenous injection of 0.5 mg of a V1 vasopressin inhibitor. None of the patients had supine changes in blood pressure or heart rate. However, upon assuming the erect position, the six patients with preexisting orthostatic hypotension had an average blood pressure fall of 44 mm Hg after vasopressin inhibition (as opposed to 20 mm Hg before), accompanied by a modest rise in heart rate of 20 beats/min. Those without autonomic dysfunction were separated into two subgroups. Four developed an average fall in orthostatic blood pressure of 18 mm Hg after vasopressin inhibition, whereas the remaining six had no change. There were no distinguishing hormonal characteristics (vasopressin, renin, and catecholamine levels) between the groups, but in the patients with autonomic dysfunction, the renin level failed to rise when upright. We conclude that vasopressin plays an important role in preventing or minimizing orthostatic hypotension in diabetic patients. Its pressor contribution is crucial in those with autonomic insufficiency and impaired renin and sympathetic responses, in whom the pressor effectiveness of vasopressin is greatly enhanced. PMID- 3346063 TI - Evaluating hyperfiltration with glycine in hypertensive rats with renal ablation. AB - Hypertension-induced renal damage is mediated by increased glomerular pressure and flow. These alterations have been evaluated by the renal response to protein or amino acids. To test this assumption, we studied glomerular hemodynamic responses to glycine infusion in rats with reduced renal mass, with and without Goldblatt hypertension. The left kidney was ablated by two thirds in 12 rats, and in 5, hypertension was induced by clipping the right renal artery. Seven normal, unmanipulated rats served as controls. Micropuncture was performed in the left kidney during control and 15% glycine infusion periods, 45 days after surgery. Arterial pressure was higher in hypertensive rats (160.3 mm Hg) than in controls (103.8 mm Hg) and rats with renal ablation (125 mm Hg; p less than 0.05). Higher values of single-nephron glomerular filtration rate and single-nephron plasma flow in rats with renal ablation (63.0, 223.7 nl/min) and hypertension (46.1, 239.7 nl/min) than in controls (28.8, 94.9; p less than 0.05) demonstrated the presence of hyperfiltration. However, glomerular pressure was elevated only in hypertensive rats (40.1 mm Hg), when compared to controls (32.7 mm Hg; p less than 0.05) and rats with renal ablation (33.4 mm Hg; p less than 0.05). Glycine increased single-nephron glomerular filtration rate and single-nephron plasma flow in control rats by 76 and 65%; rats with renal ablation had only partial responses, 35% and 23%, respectively, whereas in hypertensive rats the response was completely abolished. Glycine detected hyperfiltration and unmasked a dysfunction of preglomerular vessels that was greater in hypertensive rats and could contribute to the rise in glomerular pressure and flow and thereby to glomerular damage. PMID- 3346062 TI - Vasopressin and arterial pressure regulation. Special lecture. AB - Data from conscious rats, dogs, and humans show that plasma arginine vasopressin (AVP) begins to exert vasoconstrictor activity at concentrations in the same range as those associated with maximum antidiuretic activity. Minimum pressor responses are observed with elevated plasma AVP, due in part to decreases of cardiac output and in part to withdrawal of sympathetic neural tone to various regions of the systemic circulation. These responses appear to some extent to be species-dependent. In conscious dogs, but not in rats, the fall of cardiac output is mediated by AVP stimulation of baroreceptor reflex pathways. Studies in rats indicate that AVP inhibits the sympathetic nervous system by direct action on the central nervous system. No evidence was found for inhibition at peripheral sites such as autonomic ganglia or vascular smooth muscle receptors. Also, AVP plays an important role in the regulation of arterial pressure with blood loss by direct vasoconstriction and by AVP enhancement of the strength of the baroreceptor reflex responses. The role of AVP in the long-term control of arterial pressure and in hypertension remains controversial, but plasma AVP is elevated in many experimental and human forms of hypertension. The link between plasma AVP and hypertension remains unclear because long-term elevation of AVP alone cannot sustain volume expansion or hypertension, and excess AVP does not enhance hypertension produced by sodium-retaining hormones or other vasoconstrictor agents. It appears that AVP plays mainly a permissive role by its fluid-retaining effects in most forms of hypertension. It is also possible that it acts as a central nervous system neural transmitter and modifies autonomic pathways in some forms of hypertension. PMID- 3346064 TI - Angiotensin analogues that selectively augment the force of contraction of the isolated heart. AB - Angiotensin II (Ang II) produces a positive inotropic effect on the heart; however, its usefulness as an inotropic agent is limited because of its inherent vasoconstrictor action. We therefore designed Ang II analogues that are potent, positive inotropic agents with minimal myotropic properties. Replacement of the proline residue in position 7 with alanine reduced the pressor and vascular contractile response to less than 1% of Ang II. In spite of negligible vascular actions, however, [7-alanine]Ang II produced 50% of the inotropic activity of Ang II in the cat papillary muscle. The results of pharmacological evaluation of various position 7-substituted analogues were as follows: 1) Replacement of proline in position 7 of angiotensin I (Ang I) and Ang II with primary amino acids produced cardiac-specific, positive inotropic properties. 2) The selectivity of positive cardiac inotropic activity of position 7-substituted analogues of Ang II was dependent upon the nature of the amino acid in position 1. Replacement of aspartic acid in position 1 with sarcosine increased vasoconstrictor activity, thereby diminishing cardiac selectivity. However, this change did not affect cardiac selectivity in Ang I analogues. 3) Introduction of any type of steric hindrance in position 7 (e.g., replacement of alanine with N methyl- or alpha-methylalanine) led to a considerable loss in inotropic activity. In conclusion, contrary to rigid, structural requirements (solution conformation) for the pressor action of Ang II, a less organized structure or a random conformation at the carboxyl terminus appears to favor cardiac-selective contractile response (or positive inotropic response). PMID- 3346065 TI - Contribution of vasopressin in dexamethasone-induced hypertension in rats. AB - Our previous finding that dexamethasone-induced hypertension in rats is associated with enhanced reactivity of mesenteric arteries to arginine vasopressin but not to angiotensin II (Ang II) or norepinephrine has led us to postulate that vasopressin contributes to the development or maintenance of glucocorticoid-induced hypertension. To test this view, we investigated the effects of vasopressin, Ang II, norepinephrine, and the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP on mean arterial blood pressure and heart rate with and without ganglionic blockade with hexamethonium and angiotensin I (Ang I) converting enzyme inhibition with MK 421 in pentobarbital-anesthetized rats made hypertensive by treatment with dexamethasone (1.8 mg/kg/wk for 14 days). Administration of vasopressin, Ang II, or norepinephrine (0.003-3 microgram i.v.) produced a dose-related increase in arterial blood pressure. The pressor response to vasopressin, but not to Ang II or norepinephrine, was greater in dexamethasone treated than in vehicle-treated animals, and this difference became more pronounced in rats that received hexamethonium and MK 421. Administration of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP significantly reduced arterial pressure in dexamethasone-treated but not in vehicle-treated animals. Hexamethonium and MK 421 reduced arterial blood pressure in dexamethasone-treated as well as in vehicle-treated rats; however, arterial blood pressure remained higher in the former. Administration of the vasopressin V1 receptor antagonist produced a greater reduction in arterial blood pressure in dexamethasone-treated than in vehicle-treated rats. These data suggest that vasopressin contributes to glucocorticoid-induced hypertension, which is probably due to enhanced vascular reactivity to the peptide. PMID- 3346066 TI - Baroreceptor reflex modulation by vasopressin microinjected into the nucleus tractus solitarii of conscious rats. AB - To determine whether the central vasopressinergic system at the level of nucleus tractus solitarii (NTS) modulates the reflex control of heart rate, we employed a new method for microinjection into the brainstem of conscious, freely moving rats. Baroreceptor reflex function was assessed during pressure changes induced by intravenous administration of phenylephrine (0.25-8 micrograms/kg) and sodium nitroprusside (0.5-16 micrograms/kg) in rats microinjected, through a permanent cannula into the brainstem, with saline, arginine vasopressin (AVP), or an AVP blocker. Baseline levels of pressure and heart rate were not changed by either peptide pretreatment. Restricted injection of AVP (20 ng-0.2 microliter) into the NTS attenuated the reflex bradycardia during pressure increases, with an upward displacement of the baroreceptor reflex function line (p less than 0.01) without change in the sensitivity. Local blockade of endogenous AVP, d(CH2)5Tyr(Me)AVP (1 microgram-0.2 microliter), depressed baroreceptor reflex sensitivity with intense bradycardia to either small or large pressure increases. Baroreceptor reflex control of heart rate in response to decreases in pressure was preserved during pretreatment with AVP, whereas endogenous blockade of AVP increased baroreceptor reflex sensitivity. These effects were specific to the NTS, since in another four rats there were no effects when the injections were made 1 mm above, into the cerebellum. The changes in baroreceptor reflex control of heart rate in conscious, unrestrained rats caused by administration of AVP and its endogenous blockade provide evidence that central vasopressinergic synapses at the NTS are important physiological modulators of baroreceptor reflex function. PMID- 3346067 TI - Implication of leumorphin in inhibitory control of vasopressin secretion in conscious rats. AB - The effects of leumorphin, a kappa-agonist derived from proenkephalin B (neoendorphin and dynorphin precursor), on vasopressin secretion were studied under basal and stimulated conditions in conscious, unrestrained rats. Intracerebroventricular injection of leumorphin (60 or 600 pmol) significantly inhibited basal vasopressin secretion. The vasopressin response induced by intracerebroventricular injection of angiotensin II (100 pmol) was significantly suppressed, in a dose-dependent fashion, by the simultaneous intracerebroventricular injection of leumorphin (6, 60, or 600 pmol). Intravenous pretreatment with naloxone (0.5 mg/kg body weight) diminished the inhibitory action of leumorphin (60 pmol) on vasopressin secretion. Moreover, naloxone (0.5 mg/kg body weight) prolonged the vasopressin secretion induced by intracerebroventricular injection of angiotensin II (100 pmol). These results indicate that leumorphin possesses a potent inhibitory effect on vasopressin secretion and that, alone or in combination with other endogenous opioid peptides, it plays an important role in the control of vasopressin secretion. PMID- 3346068 TI - Effects of a kinin antagonist on mean blood pressure. AB - Administration of high doses of a kinin antagonist produces an increase in blood pressure. Thus, endogenous kinins may be involved in the regulation of blood pressure. Kinins can induce the release of vasoactive substances such as catecholamines, renin, vasopressin, histamine, and prostaglandins. To determine whether the blood pressure changes induced by high doses of kinin antagonist are due to agonistic activity mediated by these vasoactive substances, we studied the effect on blood pressure of a kinin antagonist (DArg0-Hyp3-Thi5,8-DPhe7 bradykinin) administered to control, nephrectomized, and adrenalectomized rats, and to rats treated with vasopressin V1-receptor antagonist, ganglionic and alpha and beta-adrenergic receptor blockers (either separately or combined), histamine H1- and H2-receptor blockers, and indomethacin, a prostaglandin synthesis inhibitor. Blood pressure changes were monitored on awake, restrained rats. In the control rat, the kinin antagonist injected as a bolus (4 mg/kg) into the ascending aorta produced a transient biphasic blood pressure response, first a pressor effect (delta BP = 7 +/- 1 mm Hg; p less than 0.05), then a depressor effect (delta BP = -20 +/- 6 mm Hg; p less than 0.05). The pressor response to the kinin antagonist was not affected by any of the treatments; however, the depressor effect of the kinin antagonist appeared to be caused by the release of vasodilator prostanoids from the kidney, since it was not observed in the nephrectomized rats or in those treated with indomethacin. The pressor effect induced by the kinin antagonist suggests that kinins may contribute to the regulation of blood pressure. PMID- 3346069 TI - Left ventricular function in mild hypertension after adrenergic blockade. AB - We previously used the Doppler transmitral flow velocity ratio A/E (A = late ventricular filling peak velocity; E = early ventricular filling peak velocity) and the age-adjusted ratio A/E/Age to detect left ventricular filling abnormalities in untreated mild hypertension. This study is a double-blind assessment of the effect of combined alpha- and beta-blockade (labetalol) and beta-blockade alone (atenolol) on left ventricular filling in mild hypertension. Twenty-seven patients blindly randomized to labetalol (12 patients) and atenolol (15 patients) treatment completed the echocardiographic and Doppler studies. Clinical and echo-Doppler data obtained at baseline and 6 weeks after initiation of therapy showed no difference between the two groups for age (49 +/- 10 vs 46 +/- 10 years), mean blood pressure (before therapy, 118 +/- 9 vs 117 +/- 8 mm Hg; after therapy, 108 +/- 12 mm Hg), left ventricular dimensions, wall thickness, systolic function, and mean late filling velocity A. There was no significant change in left ventricular mass and mass index with labetalol (left ventricular mass, 211 +/- 36 vs 216 +/- 38; mass index, 110 +/- 17 vs 112 +/- 16) or atenolol (245 +/- 41 vs 271 +/- 65; 120 +/- 18 vs 130 +/- 35). The mean velocity E, A/E, and A/E/Age ratios significantly improved with labetalol (p less than 0.05) but did not change significantly with atenolol. The improvement in A/E and A/E/Age ratios was primarily due to an increase in early filling velocity E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346070 TI - Effect of protein malnutrition on salmonellosis and fever. AB - Protein-malnourished rats had greater numbers of bacteria in their livers and spleens compared with numbers in control rats following a sublethal intraperitoneal dose of Salmonella typhimurium. However, the febrile responses of both groups of rats to infection were similar. The ability to mount a normal febrile response does not necessarily reflect the ability of the host to contain an infection. PMID- 3346071 TI - Nutritional requirements of shigellae for growth in a minimal medium. AB - Most (about 81%) of the clinical isolates of shigellae that were tested failed to grow in a minimal medium. Of the auxotrophic isolates belonging to the four Shigella species, 98% grew in a minimal medium containing methionine, nicotinic acid, and tryptophan. The combination of methionine and tryptophan appears to be an obligatory requirement for Shigella dysenteriae serotype 1 strains, while the combination of nicotinic acid and tryptophan appears to be obligatory for serotype 2. Requirements which varied in other isolates were, however, genetically stable, indicating that the auxotypes may be useful as epidemiological markers. Cultures of shigellae in liquid minimal medium containing the above three supplements showed rapid growth and gave reasonably high cell yields. PMID- 3346072 TI - Quantitative relationship of Treponema denticola to severity of periodontal disease. AB - The Treponema denticola content of plaque was quantitatively estimated for samples taken from periodontitis patients as well as periodontally healthy subjects among two separate human populations. The populations studied included military volunteers and civilians at a university dental clinic. The plaque samples from each population were grouped according to pocket depth measurements at the collection site. A biotin-avidin enzyme-linked immunosorbent assay procedure was developed with a monoclonal antibody specific for a serovariety of T. denticola. T. denticola was present at significantly elevated levels in plaque samples collected from deep-pocket sites of patients with severe periodontitis relative to the healthy controls and a group with moderate disease. The ratio of T. denticola content per milligram of plaque in the deep pocket groups to that of the other two groups was about 2:1 for both populations. This is the first quantitative evidence of a positive relationship between a specific spirochete species and severe periodontitis. PMID- 3346073 TI - Steric hindrance of antibody binding to surface proteins of Coxiella burnetti by phase I lipopolysaccharide. AB - The exposure of surface protein antigens on virulent phase I Coxiella burnetti was compared with that on avirulent phase II cells. Although anti-phase II antibodies did not bind to the surfaces of native intact phase I cells, they bound to phase I proteins if the proteins were solubilized for sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by immunoblotting. In addition, removal of the phase I lipopolysaccharide (LPS) by trichloroacetic acid exposed surface proteins for reactivity with anti-phase II antibodies, as shown by immunofluorescence assays, direct antibody binding, and immunoelectron microscopy using protein A-colloidal gold conjugates. Based on these observations, a simple model of phase variation is proposed to explain the apparently conflicting notions of the identity of the phase II antigen(s). The model suggests that the phase I LPS sterically hinders access of anti-phase II antibodies to a multitude of shared protein antigens, any one of which may confer phase II specificity. Exposure of these shared protein antigens through the appearance of a more truncated LPS (phase II) or extraction of the smooth-type phase I LPS allows antibody accessibility and therefore confers apparent phase II serospecificity. PMID- 3346074 TI - Vaccine-induced immunity against cutaneous leishmaniasis in BALB/c mice. AB - Partially purified antigens, derived from Leishmania infantum or L. major promastigotes and isolated under reducing conditions, were used to immunize BALB/c mice. Three subcutaneous injections of the 64- to 97-kilodalton preparation in conjunction with muramyl dipeptide conferred long-lasting immunity against L. mexicana subsp. mexicana and L. major infection; they led to the development of antibodies neutralizing the infectiousness of promastigotes, induced specific delayed-hypersensitivity reactions, and generated populations of peritoneal macrophages capable of killing amastigotes. Vaccination resulted in no harmful effects, since these antigen neither exacerbated preexisting Leishmania infection nor impeded the formation of antibodies to other antigens administered concomitantly. PMID- 3346075 TI - Cerebrospinal fluid macrophage response to experimental cryptococcal meningitis: relationship between in vivo and in vitro measurements of cytotoxicity. AB - The functional abilities of macrophages from cerebrospinal fluid (CSF) have so far been little studied. We examined the acquisition of activation characteristics by CSF macrophages during the course of experimental cryptococcal meningitis. CSF macrophages developed the ability for increased reactive oxidative intermediate (H2O2) production and tumor and fungal cytotoxicity. Despite having been activated, CSF macrophages could not inhibit the growth of Cryptococcus neoformans in vitro. Immunosuppression with cyclosporine, which eliminates the natural resistance of rabbits to cryptococcal meningitis, did not prevent or diminish H2O2 production by CSF macrophages but did reduce their tumoricidal activity. Activation of CSF macrophages appears to be an integral part of the central nervous system immune response to C. neoformans in this model, but alone is insufficient to eliminate C. neoformans from the central nervous system. PMID- 3346076 TI - Protective role of magnesium in the neutralization by antibodies of Chlamydia trachomatis infectivity. AB - Neutralization of the infectivity of Chlamydia trachomatis was assessed by using polyclonal antisera and monoclonal antibodies (MAbs). Polyclonal antisera and a species-reactive MAb as well as a subspecies-specific MAb, both of which were directed toward the major outer membrane protein of C. trachomatis, reduced the number of chlamydial inclusion-forming units in an in vitro assay. Neutralization was dependent on the presence of complement. The species-specific MAb reacted with all 15 serovars by a microimmunofluorescence assay and a dot blot enzyme linked immunosorbent assay with heat-treated elementary bodies. On the other hand, this same MAb reacted with all serovars, except those in the C complex, by the dot blot enzyme-linked immunosorbent assay with viable organisms and neutralized in vitro all 10 serovars tested, except those in the C complex. When neutralization assays were performed in a solution containing Mg2+, neutralization by both polyclonal antisera and MAbs was significantly reduced. A dose response to Mg2+ supplied as MgSO4 revealed that all concentrations tested from 50 to 800 microM had some effect. Concentrations of greater than or equal to 400 microM MgSO4 completely abolished neutralization at the lowest dilution of polyclonal antisera and species-reactive MAb tested. Although Mg2+ also blocked the neutralization effect of the subspecies-specific MAb, this neutralization was not as complete as that observed with the species-reactive MAb. Addition of Mg2+ to the assay over the initial 45 min of incubation of C. trachomatis with MAb and complement showed that the organisms could be rescued to some extent over the first 30 min of incubation, after which time neutralization of infectivity could not be reversed. C. trachomatis treated with Mg2+, the species-reactive MAb, and complement were lethal to mice in an in vivo toxicity and infectivity assay, whereas mice injected with organisms incubated with the same MAb and complement without Mg2+ survived. PMID- 3346077 TI - Detection of a novel catalase in extracts of Mycobacterium avium and Mycobacterium intracellulare. AB - A novel class of catalase, which differs from the previously described M- and T catalases of mycobacteria, was detected in strains of Mycobacterium avium and M. intracellulare. Designated A-catalase, this enzyme resisted inactivation at 68 degrees C, was inactivated by 3-amino-1,2,4-triazole (aminotriazole), and exhibited no peroxidase activity. All of these properties distinguished the enzyme from T-catalase. The A-catalase exhibited a Km of 70 mM H2O2, which is between the upper and lower extremes of the ranges reported for T- and M catalases, respectively. The A-catalase appeared to be more hydrophobic than M catalase and did not react with antiserum to a representative sample of this class. The banding patterns of T- and M-catalases seen by polyacrylamide gel electrophoresis (PAGE) were essentially unaffected by the incorporation of sodium dodecyl sulfate (SDS) into the PAGE system, whereas the single band of A-catalase seen by PAGE without SDS resolved into as many as five bands in the presence of SDS; these bands were all of slower mobility than the original band. The banding pattern seen with SDS appeared to be related more to counterion charge effects than to molecular size increases that could be attributed to SDS complexed to the protein. It remains to be determined whether the multiple A-catalase bands reflect different proteins or different SDS micellar complexes of a single protein. PMID- 3346078 TI - Passive protection of chickens against Eimeria tenella infection by monoclonal antibody. AB - Monoclonal antibodies reactive with the surface of Eimeria tenella sporozoites were produced in mice. This paper concerns one of these monoclonal antibodies, designated 1073.10, which agglutinated sporozoites in vitro and lysed the parasite in the presence of complement. This treatment neutralized sporozoite infections when the treated parasites were injected into the ceca of normal chickens. Passive transfer of ammonium sulfate-precipitated 1073.10 ascites fluid into 2- to 3-day-old or 3-week-old chickens conferred protection against challenge infection with E. tenella. These studies show that serum antibody may play a role in immunity to coccidiosis and that the sporozoite surface epitope recognized by 1073.10 is a possible vaccine candidate antigen. PMID- 3346080 TI - Levels of organochlorine pesticides in human milk in Ahmedabad, India. AB - Concentrations of organochlorine compounds, i.e., alpha HCH, gamma HCH, beta HCH, p,p'-DDE, p,p'-DDT, o,p'-DDT, p,p'-DDD and PCBs were determined in 50 human milk samples collected in Ahmedabad, India during 1981-1982. The mothers' ages ranged from 18 to 30 years (mean 24 years), and they were nursing their first or second child. All 50 samples contained alpha-HCH, gamma HCH, beta HCH, p,p'-DDE, and p,p'-DDT in a concentration of 17.51, 1.62, 205.48, 244.71, and 53.43, respectively (median micrograms/kg: whole-milk basis). o,p'-DDT was found in 48 samples whereas p,p'-DDD was detected in 44 samples. The concentration of o,p' DDT and p,p'-DDD was 53.43 and 5.13 micrograms/kg (median), expressed on a whole milk basis. PCBs were absent in all samples. PMID- 3346079 TI - Protection of rabbits in an infection model of toxic shock syndrome (TSS) by a TSS toxin-1-specific monoclonal antibody. AB - An anti-TSST-1-specific monoclonal antibody (MAb 8-5-7) was tested for its protective capacity in a rabbit infection model to toxic shock syndrome (TSS). The challenge strain of Staphylococcus aureus (RN4710), which contained a plasmid encoding TSS toxin-1, was introduced into previously implanted chambers. Purified monoclonal antibody (1.25 mg of immunoglobulin G) administered parenterally 1 day before and 1 day after initiation of infection provided complete protection against the TSS-like syndrome and the mortality which occurred in unprotected rabbits. PMID- 3346081 TI - Antipyrine and metronidazole metabolism during occupational exposure to gasoline. AB - Antipyrine and metronidazole clearance was measured in 18 fuel-filling attendants by the single-sample method while the attendants were being exposed occupationally to gasoline; the measurements were repeated after 2-4 weeks with no exposure. Eighteen office workers were investigated simultaneously. The median concentration of gasoline in the breathing zone of the fuel-filling attendants during filling and cleaning operations was 270 mgm-3 (range 18-1758 mgm-3). Antipyrine clearance was 18% higher during exposure to gasoline than after 2-4 weeks of vacation (P less than 0.01), while antipyrine clearance was unchanged in the office workers. No change was found in metronidazole clearance in either group. Antipyrine clearance was on average 26% higher in the smokers than in the nonsmokers (P less than 0.05), while metronidazole clearance was similar in smokers and nonsmokers. We conclude that gasoline is an inducer of antipyrine elimination, with no impact on metronidazole elimination. This indicates that gasoline has a differential inducing effect on the hepatic drug metabolizing enzymes of man. PMID- 3346082 TI - Shoulder strain in keyboard workers and its alleviation by arm supports. AB - Keyboard work consists mostly of dynamic contractions of the small muscles of the forearms and hands. This is accompanied by continuous activity in the arm, shoulder and neck muscles keeping the head and hand in the correct position. Eliminating the weight from the arm by means of support and the position of the arms influences the electrical activity of shoulder muscles when working at a keyboard. We studied the influence of elbow angle; as well as that of different arm supports, on electrical activity of upper trapezius muscle during keyboard work in healthy workers and persons suffering from shoulder pains. The measurements were carried out in the laboratory. EMG activities, which where measured as mean square root (RMS)-values at every 100-millisecond period in trapezius muscle when working, were lower, the greater the elbow angle. Furthermore electrical activity decreased when subjects used arm supports while working. It is evident that the static load to shoulder muscles can be lowered significantly in keyboard work, when the forearms are at an angle of at least 100 degrees and by using arm supports. The most convienient and ergonomic working position can also be found individually be the method used here. PMID- 3346083 TI - Balneoclimatic prevention and treatment of vascular disorders due to vibration at the forestry workers. AB - A total of 824 chain-saw operators who were employed in felling trees in the forestry industry were exposed to local vibration, which produced peripheral blood-flow disorders and lesions in the joints and hand bones. In the last 10 years, they have undergone 24-day balneoclimatic treatment at the Kolobrzeg Health Resort. It was found that a stay in the spa and certain balneological treatments exert a favorable effect on the peripheral blood-flow disorders produced by the local vibration of chain saws. The symptoms (chills and numbing of the fingers, etc.) disappeared in nearly 40% of these workers. An improvement in the objective indices of the peripheral circulation (thermographic and plethysmographic tests) was observed in about 90% of patients treated with brine baths combined with underwater vibratory massage (rotatory) or brine baths alone. The brine bath and vibratory massage have a direct beneficial influence on the peripheral blood flow of pectoral limbs. PMID- 3346084 TI - Uptake and urinary excretion of aluminum among welders. AB - The urinary excretion of aluminum was measured in 23 welders before and after an exposure-free interval of 16 to 37 days. In addition, the concentration of aluminum in the air was measured at the work site of 16 aluminum welders on the same workday as the first urine sample was taken. The concentration of aluminum in the urine depended on both the level and duration of exposure. The postshift urinary concentration of aluminum prior to an exposure-free interval was mainly related to the current air concentration, whereas the urinary concentration of aluminum determined after the exposure-free interval was related to total exposure duration (years). Among welders exposed for less than 1 year, the half time for urinary concentration was about 9 days whereas welders exposed for more than 10 years had half-times calculated to be 6 months or longer. The results indicate that aluminum is retained and stored in at least two functional compartments of the body and is eliminated from these compartments at different rates. PMID- 3346085 TI - Visual fatigue in video display terminal operators: objective measure and relation to environmental conditions. AB - The lighting conditions, luminance, contrast, and design of the workplace were studied in video display terminal (VDT) work stations operated by a group of female VDT data-acquisition clerks. VDT-induced symptoms were assessed by means of subject answers to a questionnaire. To measure VDT-induced ocular fatigue objectively, refraction power was determined before and at the end of workshift by an infrared autorefractometer. Job-induced refraction changes were then related to visual complaints and conditions in the workplace. The results confirmed that VDT data-acquisition work can lead to temporary myopia (myopization) in a remarkable percentage of operators; a significant correlation between eye discomfort, ocular asthenopia, and myopization was also found. Illumination levels, luminance, and contrast seem to be of paramount importance regarding visual symptoms: neither asthenopia nor myopization was observed when all of these conditions were adequate. If the ergonomic design of the workplace and the viewing distance are adequate, there are also usually fewer musculoskeletal symptoms. Our results suggest that changes in the ocular refraction status before and at the end of the work-shift, as determined by an automatic refractometer, provide a good objective index of VDT-induced "ocular fatigue", which in our study proved to be significantly related to workplace conditions. PMID- 3346086 TI - Decreased serum ceruloplasmin concentration in aluminum welders exposed to ozone. AB - During an epidemiological survey on arc welders, serum copper and ceruloplasmin were determined in two groups of workers. One group consisted of aluminum welders who were divided into two groups: 13 welders working inside aluminum tanks (confined atmosphere) and 8 welders engaged in the production of vans for dump trucks (nonconfined atmosphere). The reference group consisted of 26 workers of the same plant who were not exposed to welding fumes. Ozone, the major pollutant in aluminum arc welding, was thought to be the principal factor in the significant decrease (P less than 0.01) of mean ceruloplasmin in confined welders. This decrease in the level of ceruloplasmin was still within the reference values and was not linked to age or to tobacco consumption. We found a linear relationship between ceruloplasmin concentration and the cumulated worktime along the week. This effect could be a sign in the serum of a lung reaction against oxidant activity in this type occupational exposure. PMID- 3346087 TI - Effects of noise exposure and task demand on cardiovascular function. AB - Cardiovascular effects under various noise-exposure and task-demand conditions were studied among 40 senior highschool students. The subjects consisted of 20 males and 20 females with a mean age of 16.7 +/- 0.7 years. All subjects had equivalent abacus performance ratings. Each subject was tested with a random sequence of six sessions. The time limit set for each session was 33 min. Six experimental sessions were constructed by a random combination of noise exposure (60, 85 or 90 dB (A] white noise) and task demand (task presence or task absence) variables. Blood pressure measures were taken at the beginning and ending phases of each session. A task-demand variable was defined as a conjoint of mental arithmetic (3 min) and abacus arithmetic (30 min). The results from the present study show that the effect of noise exposure on task performance is remarkable. Only noise exposure tended to influence the performance of male students in abacus arithmetic. The effect of task demand on blood pressure was higher than that of noise exposure. No interaction effect (noise exposure x task demand) on blood pressure, was found via analyses of within-subjects two-way ANOVA. PMID- 3346089 TI - Computer aid for AIDS. PMID- 3346088 TI - A mathematical model for analyzing beat-to-beat difference in the human fetal heart rate during gestation and labor. AB - We devised a model suitable for mathematical analysis of beat-to-beat differences (BBDs) in fetal heart rates (FHRs). Factor analysis was applied, using a computer system, on a specially devised model of an FHR matrix. This matrix was arranged with FHRs and BBDs at 1-beat/min intervals by rows and columns, respectively. After obtaining the BBD by subtracting the antecedent FHR from the following FHR in a given pair of two consecutive FHRs, both variables of the antecedent FHR and BBD were crossed and the number of one was recorded at the corresponding element of the matrix. This procedure was done for all pairs of FHR and BBD yielding a matrix containing the cumulative incidences. Investigated was a total of 225,282 FHRs obtained from 20 fetuses between 37 and 41 weeks of gestation, by means of a scalp-lead electrocardiograph taken during labor. As shown by clusters of BBDs in units of beats/min, three different factors become evident: fluctuation around zero bpm, plus deviations and minus deviations. The first is considered to play a role in maintaining so-called baseline FHRs, and the second and the third indicate accelerating and decelerating actions on FHRs, respectively. This analytical model is discussed with reference to the findings obtained. PMID- 3346090 TI - CADCS simulation of the closed-loop cardiovascular system. AB - A pulsatile simulator of the closed-loop cardiovascular system, designed to solve simulation, identification and control problems in a research and education context, is presented. Its implementation makes use of a command-driven interactive program for simulation of non-linear ordinary differential equations. The flexibility of the simulator is demonstrated by the results presented which refer to a basal steady-state circulatory condition as well as a transient induced by an abrupt change in peripheral resistance. PMID- 3346091 TI - Programmed protocols for magnetic resonance imaging (MRI) PMID- 3346092 TI - Quantitative analysis of intestinal electrical spike activity by a new computerized method. AB - We developed a computerized method that allows quantitative analysis of intestinal spike activity. This method was tested for a series of measurements in six fasting conscious dogs, fitted with bipolar electrodes chronically implanted along the small intestine. Data were stored on 8-channel tape recordings and digitized before computer processing. Spike detection was accomplished by means of a discriminant function able to differentiate spikes from non-spikes (e.g. artifacts) on the basis of six parameters. Computer analysis allowed accurate spike recognition (probability of incorrect classification less than 6%). Spike activity during fasting was monitored by calculating, during each phase of the migrating myoelectric complex, the following parameters per unit of time (30 s): number of spikes, percentage of spiked slow waves and number of spikes per spiked slow wave. Results were given both in tabular and graphical form. This method provides a research tool for a better quantitation of intestinal spike activity. PMID- 3346094 TI - Psychiatrists for machines. PMID- 3346093 TI - A simple program in BASIC for the one-way analysis of variance of experimental data. AB - A BASIC program is presented to compute one-way analysis of variance of life data. The program is simple, powerful, direct and relatively short. It allows for judgement of significance at the chosen confidence limit. Applications of the program to some experimental therapeutic data are shown. PMID- 3346095 TI - Statistical pattern classification of clinical brainstem auditory evoked potentials. AB - The brainstem auditory evoked potentials (BAEPs) recorded in the neurological clinic were classified using the Bayes classifier (BC) and Fisher's linear discriminant function (FLD). The latencies of initial five peaks, interpeak intervals were examined for optimum features to develop classifiers. The accuracy of classification was 85.3% when absolute latencies of peaks III, IV and V were used as features. The BC gave better performance than FLD, indicating that second order statistics of BAEPs for normal and pathological classes are different. The results of this study indicate that latencies alone give enough information for recognizing normal from pathological BAEPs, using physician's evaluation of BAEPs as the reference. PMID- 3346097 TI - Expression of the gangliosides GM3, GD3 and GD2 in tissue sections of normal skin, naevi, primary and metastatic melanoma. AB - Expression of the gangliosides GM3, GD3 and GD2 was studied in tissue sections from 19 naevi, 29 primary and 83 metastatic melanoma using the ABC immunoperoxidase technique. GM3 was not detected in normal skin whereas GD2 was detected on the basal and stratum spinosum of the epidermis and on peripheral nerves in the dermis. GD3 was expressed on melanocytes but not on most other components of normal skin. However, GD3 was strongly expressed on epidermis adjacent to naevi and primary melanoma whereas GD2, in contrast to that in normal skin, was not expressed on the epidermis adjacent to 26/29 primary melanoma. All naevi were positive for GM3 and GD3 except that GM3 was not detected on junctional components of naevi. GD2 was not expressed on naevi except in areas showing neuroid differentiation. Studies on melanoma revealed that approximately 60% of primary and 75% of metastatic melanoma expressed GM3 to a varying extent. With 2 exceptions, all primary and metastatic melanomas expressed GD3 although there was variable expression within most of the individual tumours. GD2 was detected in only approximately 25% of primary and 50% of metastatic melanomas. Both GD2 and GD3 were detected on lymphocytes surrounding melanoma. The higher expression of GD2 on metastases compared to primary melanomas was consistent with the view that GD2 expression was associated with increased metastatic potential. However, the low proportion of metastases expressing GD2 and the absence of any correlation with thickness of the primary tumour suggested that GD2 expression was not a reliable marker of metastatic potential. No differences could be detected in ganglioside expression on metastases in skin or lymph nodes. These results appear to have implications for the use of MAbs against gangliosides in therapy of melanoma and in the study of melanocytic differentiation. PMID- 3346096 TI - Diet and cancer of the stomach: a case-control study in China. AB - A case-control study focusing on the role of single food items was undertaken in the Heilongjiang area, 241 patients with histologically verified stomach cancer and an equal number of controls (with non-neoplastic diseases) matched by age, sex and area of residence being interviewed during a 2-year period. Questions asked covered economic status, occupation, histories of smoking and drinking, diet and dietary habits and disease history. Data concerning the average frequency and quantity of consumption of single food items were obtained by the same interviewer. An inverse association between the consumption of vegetables and stomach cancer was observed whereas high intake of potatoes and of salted and fermented soya paste appeared to be high-risk factors. Specifically, Chinese cabbage plays an important role in reducing the risk of developing stomach cancer. PMID- 3346098 TI - Sister chromatid exchanges and chromosomal aberrations in lymphocytes of nurses handling cytostatic agents. AB - A cohort study of 29 nurses who constantly handled cytostatic drugs, and 29 controls matched according to sex and age, was carried out between 1983 and 1986. Cytogenetic damage was assessed by sister chromatid exchanges (SCE) and chromosomal aberrations. No significant increase in mean number of SCE was found for nurses (7.37) as compared to matched controls (7.00), whereas a significant excess of SCE (p less than 0.001) was observed for smokers (8.23) as compared to non-smokers (6.75). The number of SCE was studied in relation to the amount and nature of cytostatics handled as well as to the duration of exposure. A significant association (p less than 0.05) was found between individual mean number of SCE and the total number of drugs handled after adjustment for confounding factors. In contrast, the number of SCE was not significantly related to the nature of drugs handled or to the duration of exposure. With regard to chromosomal damage, no significant difference was observed between nurses and controls in gap, break, dicentric and translocation frequencies. PMID- 3346099 TI - Occupation and lung cancer in two industrialized areas of northern Italy. AB - A population-based case-control study on lung cancer was conducted in 2 industrialized areas of northern Italy. Cases (126) were all males who died from lung cancer between 1976 and 1980. Controls (384) were a random sample of males dying from other causes during the same period. Jobs held during working life have been analyzed according to a list of occupations already known to be causally associated with lung cancer (list A) and a list of occupations suspected of being so (list B). Attributable risk percentages in the population for occupations included in either list A or B were about 36% and 12% in the 2 areas. Welders or workers in industries in which welding is common showed elevated odds ratios: 2.9 for welders (95% CI 0.9-9.8); 4.9 (1.1-22.9) for structural metal workers; 11.4 (2.6-49.9) for workers in structural metal production. Other job categories associated with lung cancer included: electricians and workers in electrical machine production, woodworkers (in furniture or cabinet making, but not in carpentry or joinery) and cleaning services. Smoking did not seem to exert a substantial confounding effect. Attributable risk percentages for tobacco smoking were about 78% and 76% in the population of the 2 areas. PMID- 3346100 TI - Occupation and risk of cancer of the lower urinary tract among men. A case control study. AB - Data from a hospital-based matched case-control study with 531 male pairs were analyzed for risks of cancer of the lower urinary tract associated with previous employment and particular occupational exposures. Statistically significant odds ratios were obtained for ever-employment as mining workers (2.0), turners (2.3), tailors (2.7), truck drivers (1.8), locomotive drivers (3.0) and janitors (3.5), whereas odds ratios of 3.0 or more, found for rubber and plastics workers, printing workers, gas workers, artists and chemists were not statistically significant. When adjusted for smoking, there was a trend toward increasing relative risks with increasing duration of employment as truck drivers and as turners, and relative risks rose 3-fold for 30 or more years of employment. With regard to a priori high-risk industries, ever-employment in the rubber, plastics and synthetics, dyestuff and paints, mining, and printing industries and secondary processing was associated with significantly higher relative risks, and a statistically significant trend in risk with increasing duration of employment was found for the first 3 industries mentioned. With regard to job-related exposures to specified substances, the relative risks observed for increasing duration of exposure suggest that exposures to petroleum, oils, chromium/chromate, spray paints, and zinc, which correspond to exposures involved in the occupations showing a higher relative risk in this study, are associated with a higher risk for cancer of the lower urinary tract. PMID- 3346101 TI - Absence of expression of a human endogenous retrovirus is correlated with choriocarcinoma. AB - We examined the RNA expression of a human endogenous provirus, termed ERV3, in 170 human tissue and cell specimens. The highest expression was found in normal placental chorionic villi as mRNAs of 9, 7.3, and 3.5 kb. The 7.3-kb RNA species was found only in the placenta. ERV3 mRNA was expressed in most other normal and malignant tissues at a level which was 2-10% of that seen in placenta. However, several tissues and tumor cell lines had higher transcriptional levels, equal to 10-60% of the placental level. In contrast, an almost complete abrogation of ERV3 mRNA expression was noted in choriocarcinoma cell lines and in an invasive hydatidiform mole tissue biopsy. This abrogation was not linked to deletions or rearrangements of the ERV3 genome. It appeared to be unassociated with methylation because the ERV3 provirus was similarly methylated in the DNA of placental chorionic villi and choriocarcinoma cells, and ERV3 transcription in choriocarcinoma cells was not induced by 5-azacytidine. These results suggest that the loss of ERV3 mRNA expression is associated with susceptibility to choriocarcinoma. PMID- 3346102 TI - Tamm-Horsfall protein is a marker of renal and extra-renal rhabdoid tumours. AB - A monoclonal antibody (MAb) to Tamm-Horsfall protein (THP) was used to stain 6 renal rhabdoid tumours (RRT) and 2 primary extra-renal rhabdoid tumours (E-RRT). One of the E-RRT was a tumour from the posterior fossa of a 3-year-old child and the other was a lump from the right side of the neck in an 18-month-old girl. Five of 6 RRT and both cases of E-RRT were positive for THP. Both cases of E-RRT also reacted with vimentin and cytokeratin MAbs. On electron microscopy, cells from both E-RRT were seen to contain concentric whorls of intermediate filaments characteristic of rhabdoid tumours. Viable tissues from one RRT and one E-RRT (the posterior fossa tumour) were available for tissue culture. Ninety-five percent of the cells growing out of both tumours were polygonal and approximately 5% of these cells were THP-positive. PMID- 3346103 TI - Methylxanthines and breast cancer. AB - The association between intake of methylxanthines and risk of breast cancer was examined in this population-based case-control study conducted in Adelaide, South Australia. The study included 451 cases, and one control was matched to each case for age (to the nearest year). Overall, and within the post-menopausal stratum, there was relatively little variation in the risk of breast cancer in association with total caffeine and total methylxanthine intake. In pre-menopausal women, risk was increased at the higher levels of intake, but the increase in risk was not dose-dependent. There was no evidence for an effect of methylxanthines at high levels of fat intake. Prior epidemiological and experimental studies have not provided strong support for a positive association between intake of methylxanthines and risk of breast cancer. However, the possibility that they are linked through an association between methylxanthines and those histological subcategories of benign breast disease which are strongly associated with risk of breast cancer is discussed. PMID- 3346104 TI - Loss of alleles on chromosome 18 and on the short arm of chromosome 17 in polyploid colorectal carcinomas. AB - The zygosity of 19 colorectal carcinomas (either near-diploid or polyploid) from patients known to be heterozygous for RFLPs located on chromosome 18 or on the short arm of chromosome 17 has been examined. In most cases, at least one allele was significantly under-represented. The reason for the absence of complete loss of heterozygosity was investigated for 5 polyploid tumors. It was shown that the diploid component which, in these tumors, is essentially composed of non neoplastic cells, remains heterozygous as the polyploid component invariably loses heterozygosity. The results strongly suggest that many colorectal carcinomas originate from a single cell which had lost at least part of either chromosome 18 or of one short arm of chromosome 17, or both. PMID- 3346105 TI - Aminoterminal propeptide of type-III procollagen in serum--an indicator of clinical behavior of advanced ovarian carcinoma? AB - In ovarian carcinoma, elevated serum concentrations of the aminoterminal propeptide of type-III procollagen are related to the clinical stage of the disease and to the presence of ascites, which contains very high concentrations of the propeptide. In a follow-up of patients with advanced disease, favorable clinical course was associated with normalizing propeptide values, whereas in progressing disease the values increased several weeks before clinical progression. In stable disease the concentrations were constantly above the reference range. Laminin and type-IV-collagen-related serum antigens were mostly within the reference range. PMID- 3346106 TI - Role of concomitant resistance in the development of murine lung metastases. AB - An attempt was made to explain the distinct lung metastatic patterns of 2 mammary adenocarcinomas with a common BALB/c origin: M3, which does not induce spontaneous metastases, and MM3 with an almost 100% incidence. No difference between the 2 tumors was detected with respect to host mononuclear cell content, degree of immunogenicity or lung-colony-forming ability. Conversely, there was a marked difference in the capacity to induce concomitant resistance: M3-bearing mice induced stronger and earlier resistance against i.v. challenge of both M3 and MM3 tumor cells than MM3-bearing mice; this resistance was expressed as lower number of lung metastases and lower tumor-cell proliferation in metastatic nodules. M3 was also able to control the development of spontaneous metastases: metastases developed in all M3-excised mice, compared with none in M3-bearing mice, while MM3-bearing mice also bearing a secondary M3 tumor developed fewer metastases than mice bearing MM3 only. This anti-metastatic effect does not appear to depend on classical immunological mechanisms since no difference could be detected between the 2 tumors in response to T cells, NK, macrophages or antibodies. PMID- 3346107 TI - Inhibitory effect of prolonged administration of cysteamine on experimental carcinogenesis in rat stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine. AB - The effect of cysteamine (2-aminoethanethiol hydrochloride) on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N nitrosoguanidine (MNNG) was investigated in inbred Wistar rats. Prolonged administration of 25 or 50 mg per kg body weight of cysteamine after treatment with MNNG for 25 weeks significantly reduced the incidence and number of adenocarcinomas of the glandular stomach. Histological examination showed that the adenocarcinomas that did develop in rats treated with these 2 doses of cysteamine had high mucin-producing activity. Furthermore, treatment with cysteamine caused significant increases in serum gastrin level and gastric acid secretion, together with significant decreases in the antral mucosal pH and the labelling indices of pyloric and oxyntic gland mucosae and gastric cancer. These findings indicate that cysteamine inhibits the development of gastric adenocarcinomas and that its effect may be related to decreasing proliferation of cells in the gastric mucosae. PMID- 3346108 TI - Thromboplastin release, but not content, correlates with spontaneous metastasis of cancer cells. AB - No previous studies on the possible contribution of cancer-cell procoagulants to metastasis have fulfilled all the criteria for attaining biologically relevant and readily interpretable data (Grimstad et al., 1986), viz: (1) Spontaneous metastasis from primary tumors should be assessed in syngeneic animals; (2) cloned cell lines should be used to correlate cell properties, because heterogeneity within the cell lines employed is a source of serious error; (3) enough clones, derived from the same original tumor, should be used to identify only nonrandom correlations. Observing these criteria, we examined the procoagulant activities of 19 murine fibrosarcoma cell clones and 4 uncloned cell lines with high to moderate or low potential for lung metastases formation. The procoagulant activity found was exclusively of the thromboplastin (tissue factor, factor III) type. It occurred in all cell homogenates, but the quantities did not correlate with metastatic potential. In contrast, all highly to moderately metastatic cell clones and lines from 2 different fibrosarcomas shed thromboplastin activity into the culture medium, whereas no weakly metastatic cells did. Histological examination further supported these indications that release of thromboplastin from cancer cells can promote metastasis by initiating blood clotting and thereby facilitating arrest of the cancer cells in target organ vessels. Examination of a third fibrosarcoma showed that release of thromboplastin activity is not necessary for metastasis in all tumors. PMID- 3346109 TI - Changes in plasma gangliosides in relation to tumor growth and their tumor enhancing effect. AB - Gangliosides in the plasma of Ehrlich ascites tumor-bearing mice showed changes, both quantitative and qualitative, with progress of tumor. Quantitative changes assessed by chemical estimation indicated a gradual increase of gangliosides up to day 6 of tumor growth followed by a decline leading to a level below the normal by day 12. Qualitative changes studied by thin-layer chromatography indicated appearance of new gangliosides in the plasma of tumor-bearing mice, which were absent from normal plasma. One of these gangliosides appears to be of tumor-cell origin. Gangliosides obtained from tumor-bearing mouse plasma enhanced tumor growth when adoptively transferred with tumor cells into normal mice. PMID- 3346110 TI - A new experimental metastasis model in athymic nude mice, the human malignant melanoma LOX. AB - The human tumor line LOX was established as an s.c. xenograft in nude mice from a lymph-node metastasis of a patient with malignant melanoma. I.v. injection into adult nude mice of single-cell suspensions prepared from xenografts resulted in progressively growing lung tumor colonies that killed the animals. No difference in colony formation was seen between cells taken from lung colonies and s.c. xenografts. An in vitro cell line, LOX-L, was established from lung colonies, and the monolayer cells, detached with EDTA, retained the same ability to form experimental lung metastases. In a total of 14 experiments, 82 of 89 mice receiving 1 X 10(6) viable tumor cells died with a mean survival time of 34.1 +/- 4.8 days. Long-term passaging in vivo and in vitro did not result in any alteration of the lung-colonizing potential of the LOX cells, whereas trypsinization of the cells before i.v. injection reduced lung colony formation. The life span was inversely related to the number of LOX cells injected, permitting estimation of the cell kill caused by chemotherapy. Mice injected i.v. with the LOX cells showed the same relative response to cis diamminedichloroplatinum (CDDP) and mitozolomide (MZA) as did animals carrying s.c. xenografts. The LOX cells have shown a remarkable stability and similarity to the cells of the patient's tumor with respect to morphology, karyotype and chemosensitivity. The LOX model may be useful for testing effects of therapy on lung micro- and macrometastases, and the activity of antimetastatic agents, as well as for studying mechanisms involved in the metastatic process. PMID- 3346111 TI - Effects of metastatic cascades on metastatic patterns: studies on colon-26 carcinomas in mice. AB - The present studies are based on autopsy data showing that in upper esophageal and lower rectal carcinomas, hematogenous metastasis occurs mainly first to the lungs, and cancer cells from pulmonary metastases generate arterial metastases. In lower esophageal and upper rectal carcinomas, hematogenous metastases occur first in the liver, then in the lungs, and are further disseminated by the arterial route. The arterial metastatic patterns are different in the 2 groups. One possible explanation for these differences in pattern is that liver "residence" is associated with different metastatic behavior; this has been tested in a model system. Experiments with the transplantable colon-26 carcinoma in mice reveal that, when cancer cells from common s.c. transplant sites are grown in the liver, lungs or liver-and-lungs, and then injected into the bloodstream of fresh recipients via the left ventricle, the portal vein or the tail vein, different patterns and degrees of colonization of 11 different target sites are observed. These results are consistent with the hypothesis that growth of cancers in different anatomic sites may modify the subsequent arterial metastatic patterns, due to site-induced changes occurring in cancer cell populations, which influence metastasis from metastases or so-called "cascade" processes. PMID- 3346112 TI - Establishment and characterization of cisplatin-resistant sublines of human lung cancer cell lines. AB - Human lung cancer sublines resistant to cisplatin (CDDP) have been developed by continuously exposing cells to gradually increasing doses of CDDP and use of the limiting dilution technique. The cell lines used were PC-7, PC-9 and PC-14 (pulmonary adenocarcinoma) and H69 and N231 (small-cell lung cancer). The resistant phenotype of the resistant sublines was stable for more than 2 months in the absence of drug. PC-7/1.2 (i.e., PC-7 cells growing stably in medium containing 1.2 micrograms/ml of CDDP), PC-9/0.5, PC-14/1.5, H69/0.4, and N231/0.2 have been developed, which are 22.9, 7.1, 3.1, 25.6, and 8.4 times more resistant to CDDP than the respective parent cell line in terms of IC50 in the soft agar colony assay with continuous drug exposure. Cloning efficiency decreased significantly in N231/0.2. The doubling times increased significantly in most of the resistant sublines. Cellular DNA contents increased in all resistant sublines, but statistical significance was observed only in H69/0.4 (p less than 0.05). Cells of the resistant sublines of PC-7, PC-9, PC-14 and H69 were larger than cells of the parent lines, but the differences were not significant. The growth morphologies of all resistant sublines in the drug-free medium were similar to those of parent cell lines. All resistant sublines tested were significantly cross-resistant to carboplatin. The patterns of cross-resistance, cross-sensitivity and collateral sensitivity to adriamycin, mitomycin-C, 5 fluorouracil, vindesine, etoposide, aclacinomycin and vincristine were different in each resistant subline. Verapamil (3.3 micrograms/ml) showed little modifying effect on CDDP resistance in 5 CDDP-resistant sublines tested except N231/0.2 (Modification Index: 0.49). Cyclosporin A (5.0 micrograms/ml) modified CDDP resistance in CDDP-resistant small-cell lung cancer sublines (H69/0.4 and N231/0.2) (Modification Index: 0.45 and 0.07, respectively), while in CDDP resistant NSCLC sublines (PC-7/1.0 and PC-9/0.5), cyclosporin A reduced the sensitivity to CDDP. PMID- 3346113 TI - Overlooked, overworked: women's unpaid and paid work in the health services' "cost crisis". AB - Dewaging shifts work from the marketplace to the household. The shift seems a short-term strategy used by capitalists, governmental policy-makers, and managers to reduce the wage bill for service workers in such areas as schooling, retailing, health services, and banking. In health services, the expansion of women's unpaid nursing in the household and a new labor process among paid nursing workers are necessary for new corporate and federal cost-containment strategies. Registered and licensed nurses, nurse's assistants and aides see their jobs eliminated, expanded, or moved from one work site to another. Increased use of outpatient clinics, in-and-out hospital stays of less than one day, and shortened hospital stays mean sick people in their homes, not hospitals. The work of caring for the sick does not disappear, however, though people may go without. Much nursing work is shifted to patients and to their families, and even to friends and neighbors. Within the family, women's unwaged work is central, supporting the new labor process among paid nurses. Wives, mothers, daughters, friends, etc., do the work once done for pay in clinics and hospitals. PMID- 3346114 TI - Workers' participation and occupational health: the French experience. AB - In France, workers' participation in occupational health was organized for the first time in 1947, when Hygiene and Safety Committees were created. However, these committees remained ineffective in many firms for more than 20 years. Their role and power were greatly extended in 1976; in 1982, the Auroux Laws gave wage earners new rights, mainly rights of expression. Here too, the way these laws have been put into operation varies a lot. Generally speaking, a great many regulations and laws exist that should give workers very good protection, but control systems are weak, and wage-earners' information on health is insufficient. Workers' participation is generally set up through trade unions, which are more often nationwide than locally organized. Workers' membership in unions is rather weak. The recent creation and development of quality circles in many firms, controlled by the company, give a false impression of workers' freedom of speech and do not really improve participation. But recent social movements have shown that people increasingly wish to express themselves and to deal with their own employers without any go-between. Nevertheless, participation will become effective only if workers' knowledge is taken into account, if they are trained in analysis and expression, and if their suggestions are seriously considered. PMID- 3346116 TI - The well baby lottery: motivational procedures for increasing attendance at maternal and child health clinics. AB - A lottery system was used to improve attendance at four well baby clinics in four colonias in Tijuana, Mexico. Mothers earned one lottery ticket for each visit to each clinic during the intervention period. At the end of each month, ticket receipts were entered into drawings for one of three bags of groceries. The lottery system was evaluated within a "multiple baseline design" whereby the intervention was staggered across the four clinics on a month-by-month basis. Although attendance was not enhanced uniformly, an overall improvement of 25 percent was realized. The lottery system was at times hampered by administrative problems, such as the breakdown of a public address system used to announce the open hours of a clinic in one of the colonias. PMID- 3346115 TI - The Mandwa project: an experiment in community participation. AB - The project at Mandwa was designed to study the problems of health in rural India and the delivery of health care by the existing public and private health systems. The results demonstrate the important role of socioeconomic and political factors not only in vital areas such as nutrition, water supply, sanitation, and housing, but also in the delivery of health services. The private sector showed a predominantly curative and monetary orientation, while the public sector demonstrated a lack of accountability to the people it was designed to serve. Under these conditions, an attempt was made to test the possibility of training local women in self-help with a minimal supportive service. The results reveal that adequate knowledge and technology exist for most of the prevalent problems of health and illness in developing countries, and that semiliterate villagers have the capacity to use these effectively if they are provided in a simple manner. This experiment also demonstrates the opposition from local vested interests to any change of the status quo, even in the relatively noncontroversial field of health. PMID- 3346118 TI - The Matthew Effect in science. PMID- 3346117 TI - Women and children at risk: a feminist perspective on child abuse. AB - Viewing child abuse through the prism of woman battering reveals that both problems originate in conflicts over gender identity and male authority. Data indicate that men, not women, typically commit serious child abuse. A study of the mothers of child abuse victims shows that battering is the most common context for child abuse, that the battering male is the typical child abuser, that the battered mothers have no distinctive pathology in their backgrounds, and that clinicians respond punitively to the battered mothers. The child abuse establishment assigns responsibility for abuse to mothers regardless of who assaults the child, and responds punitively to women, withholding vital resources and often removing the child to foster care, if women are battered or otherwise fail to meet expectations of "good mothering." The combination of male control, misleading psychological knowledge about women's propensity for "bonding," and sanctions used to enforce gender stereotypes of motherhood combine to increase the entrapment and inequality from which battering and child abuse originate, a process termed "patriarchal mothering." The best way to prevent child abuse is through "female empowerment." PMID- 3346119 TI - Once, twice, thrice--how many times a day for a topical steroid? PMID- 3346120 TI - Melasma in men. A clinical and histologic study. AB - Melasma is characterized by a facial hypermelanosis of light to dark brown color, being more common in women of Hispanic origin. In this study, 27 men with melasma were evaluated clinically and histologically to compare their features with those of previous studies. Three patterns of localization were recognized, namely, centrofacial, malar, and mandibular. On the basis of Wood's light examination, an epidermal, a dermal, and a mixed type were identified. Epidermal hyperpigmentation only and epidermal and dermal hyperpigmentation were found in histologic analysis of the cases. Significant etiologic factors included exposure to sunlight in 66.6% as well as a familial predisposition in 70.4% of the cases. This study demonstrated that melasma in men shares the same clinicohistologic characteristics as in women, but hormonal factors do not seem to play major significant role. PMID- 3346121 TI - Disseminated sporotrichosis. AB - The clinical manifestations of sporotrichosis can be classified into three disease patterns: (1) localized lymphatic sporotrichosis, (2) fixed cutaneous (or endemic) sporotrichosis, and (3) disseminated sporotrichosis. This presentation reflects a rare disseminated form of the disease with extensive cutaneous and systemic lesions, and further illustrates the difficulty in diagnosing systemic sporotrichosis infection. PMID- 3346122 TI - Orf and pregnancy. AB - A 31-year-old woman presented with orf on the forefingers at 34 weeks of gestation. The disease, contracted after handling sheep a week before, was uncomplicated, and the patient gave birth at term to a normal baby. Although some cases with features suggestive of viremic spread had been described, the authors find an overall benign picture of orf in man and recommend symptomatic therapeutic measures. PMID- 3346124 TI - Varicella complicated by staphylococcal scalded skin syndrome with unusual necrosis. PMID- 3346123 TI - Eosinophilic pustular folliculitis in a patient with AIDS. PMID- 3346125 TI - Cellular angioma of infancy with dermal melanocytosis. PMID- 3346126 TI - Cutaneous rhinosporidiosis mimicking verruca vulgaris. PMID- 3346127 TI - The clinical and epidemiologic features of tropical ulcer (tropical phagedenic ulcer). AB - A comparative survey of patients with tropical ulcer has been carried out in Zambia, Gambia, Southern India and Papua New Guinea. The clinical features, socioeconomic background and nutritional correlates have been compared in 170 patients. In 96% of cases the condition occurred on the foot or lower leg. In only 10 instances did the ulcer last for over six months. There was one patient with a squamous cell carcinoma arising in situ from the ulcer margin. No significant differences in clinical features were seen in the countries surveyed. In all areas apart from southern India most cases were seen in the rural population and in children or teenagers. There was no correlation between the development of an ulcer and nutritional status found in this survey. Evidence is presented that there is an association between tropical ulcer and exposure to mud or slow moving fresh water. PMID- 3346128 TI - Erosion of psoriatic plaques after chronic methotrexate administration. AB - A 43-year-old white man developed a shallow erosion of a psoriatic plaque after chronic administration of methotrexate. This unusual cutaneous sign may be the first sign of methotrexate toxicity. PMID- 3346130 TI - Mortality from nonmelanotic skin cancer. PMID- 3346129 TI - Darier's disease: successful response to synergism of vitamins A and E. PMID- 3346131 TI - A simple and cheap coagulator. PMID- 3346132 TI - Inflammatory linear verrucous epidermal nevus. PMID- 3346133 TI - Molluscum contagiosum. PMID- 3346134 TI - Corneal tissue preservation. PMID- 3346136 TI - Emergency medical services in rural Iowa. PMID- 3346135 TI - Recurrent erosion. PMID- 3346137 TI - Emergency medical services in urban Iowa. PMID- 3346138 TI - Considerations in aeromedical transport. PMID- 3346139 TI - Market dynamics and the pricing process. PMID- 3346141 TI - Iowa emergency medical services: funding the future. Iowa Department of Public Health. PMID- 3346140 TI - Sunscreens. PMID- 3346142 TI - The "ruler sign"--a semiquantitative physical sign of chronic obstructive pulmonary disease. AB - This report describes a simple and reproducible physical sign of chronic obstructive pulmonary disease--the "ruler sign." With the patient standing erect, a ruler is placed on the trapezius muscle and the clavicle at the midclavicular line. The ruler forms an angle with the horizontal line. At the end of a normal expiration this angle was 36 degrees +/- 4 SD in healthy control subjects as compared with 15 degrees +/- 4 SD in patients with severe chronic obstructive pulmonary disease. A simple device is described that enables convenient measurement of this angle at the bedside. PMID- 3346143 TI - Frozen saphenous vein allografts for constructing vascular access for hemodialysis. AB - Frozen saphenous vein allografts were used in seven patients to construct vascular access for hemodialysis. In five patients the allografts connected the brachial artery to the axillary vein, and in two, the radial artery to the basilic vein. Five allografts functioned for periods varying from 6 to 20 months, one is still functioning after 3 years, and one graft occluded immediately following surgery. The availability of this biological material, the ease of its preparation, the very low cost, and the satisfactory graft survival, call for further evaluation of this method for complex vascular access problems in patients on chronic hemodialysis. PMID- 3346144 TI - Increased uric acid clearance in the syndrome of inappropriate secretion of antidiuretic hormone. AB - Twenty-eight elderly inpatients with severe hyponatremia were investigated prospectively to determine if fractional uric acid clearance was increased significantly in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) compared with other causes of hyponatremia. The patients were divided into three groups: Group A--hyponatremia due to SIADH, Group B--hyponatremia due to diuretic use, and Group C--hyponatremia possibly due to a number of causes. Serum uric acid was 3.2 +/- 0.4 and 5.3 +/- 0.6 in Groups A and B, respectively (P less than 0.05). Fractional clearance of urate in Groups A and B were 43 +/- 5.1 and 16.7 +/- 1.9, respectively (P less than 0.001). In Group C six of the nine had abnormally increased fractional clearance of uric acid (31.6 +/- 3.8) in addition to accepted biochemical criteria of SIADH. In 10 patients with SIADH, urate clearance measured before water restriction was 40.2 +/- 9.0%, and after serum sodium returned to normal 11.6 +/- 1.5 (P = 0.05). Of the total 28 patients 17 had increased fractional uric acid clearance with biochemical criteria of SIADH, suggesting that this syndrome is a common cause of the increased susceptibility to hyponatremia among older patients. PMID- 3346145 TI - HLA antigens in patients with Heberden's nodes. AB - Tissue typing was performed on a group of 51 patients with Heberden's nodes (HN) (45 Ashkenazic and 6 non-Ashkenazic Jews). The frequency of HLA-DR2 was higher (P = 0.03) in the Ashkenazic patients than in the Ashkenazic controls. However, the association was not significant after correction for the number of tested alleles at that locus. In the second part of the study, HLA typing was performed on subjects from a family with multiple HN occurrences. Of the 13 family members typed, 9 had HN: 6 of these had the haplotype A2, Bw35, DR2. We conclude that the development of HN may be influenced by genetic factors. Our results may suggest an association between HN and HLA-DR2 in Ashkenazic Jews. PMID- 3346146 TI - HLA and schizophrenia in Israel. AB - Thirty-two Israeli Jewish schizophrenic patients were typed for Class I (HLA-A, B, C) and Class II (HLA-DR) antigens. A significant increase of HLA-A2 (P = 0.01) and A23 (P = 0.02) was found. None of the 10 HLA-DR antigens tested was associated with the disease. Study of eight families indicated that close linkage of the gene responsible for this disorder to the HLA system is unlikely. PMID- 3346147 TI - Screening for depressive symptoms among the elderly in Israel. A reliability and validity study. AB - The Hadassah Elderly Depression Screening Scale (HEDSS)--a modified version of Zung's Self-Rating Depression Scale and Beck's Depression Index--was developed for use among the elderly in Israel. In a sample of 183 elderly residents of Jerusalem, the scale proved to be highly reliable and able to differentiate between persons diagnosed as depressed and those defined as healthy. Moreover, it was found to be valid among subpopulations grouped by sex, education and ethnicity. Various cutoff points were tested for targeting screening at specific populations. PMID- 3346148 TI - Relationship between head dimensions and body length in the context of mental retardation. AB - The relationship and possible disproportion between different cranial dimensions- head length, head circumference and biparietal diameter--body length and developmental status in normocephalic children were studied in 166 mentally retarded and 471 normal control subjects, between the ages of 3 months and 6 years. When the total cohort was analyzed, all dimensions, particularly head length, were found to be significantly reduced in the study group compared with the controls. Stratification into three age-groups revealed that in the 3- to 15 month-old subjects, head length was the most significantly reduced dimension, while in the older children body length was more significant, followed by head length. Further discriminant analysis resulted in a formula consisting of only three factors--body length, head length and age. Head circumference and biparietal diameter were noncontributory. This investigation did not support the concept of a disproportionately small head compared with height in normocephalic mentally retarded children, but rather a general growth failure mostly affecting height and head length. PMID- 3346149 TI - Osteoclast-like cells grow in cultures of multipotent hematopoietic progenitors in thrombocytopenia and absent radii (TAR) syndrome. AB - Cultures of bone marrow multipotent hematopoietic progenitors were performed in a case of TAR syndrome and normal bone marrow. It was found that clones of large multinucleated cells formed after 2 weeks of cultures from the TAR bone marrow but not in that of control subjects of the same age. Those cells contained a tartrate-resistant acid phosphatase activity and were negative for both monocytes and megakaryocytic markers. The data suggest that the multinucleated cells have several characteristics of osteoclasts. It was also found that growth of multipotent and megakaryocytic colonies was reduced when compared with normal control subjects (36 and 24%, respectively). This new finding of osteoclast or osteoclast-like cells derived from cultures of bone marrow hematopoietic precursors in TAR syndrome is discussed in relation to the lack of megakaryocytic characteristics in this disorder. PMID- 3346150 TI - Metabolic studies in a patient with idiopathic hypophosphatemic osteomalacia. AB - Studies were conducted in a patient with idiopathic hypophosphatemic osteomalacia to delineate the roles of parathyroid hormone (PTH), vitamin D and renal tubular function. A 43-year-old woman presented with progressive skeletal pains resulting in severe incapacity. Workup revealed: hypophosphatemia with a low tubular maximal phosphate reabsorption per glomerular filtrate (TmP/GFR) of 1.05 mg/dl, normocalcemia, hypocalciuria, elevated alkaline phosphatase and glycinuria. PTH and urinary cyclic AMP (UcAMP) were normal, while calcitriol was low. Renal tubular acidosis or other transport defects were not present and no tumor was found. Biopsy was diagnostic for osteomalacia, and the patient responded to 1 alpha OHD3 and phosphate therapy. Hyperparathyroidism was ruled out by 1) normocalcemia persisting after 1-alpha OHD3 and calcium loading and 2) normal PTH and UcAMP challenged by phosphate supplements. Combined calcium and 1-alpha OHD3 administration resulted in hypercalciuria, decreased UcAMP and increased, but not corrected, TmP/GFR. These findings suggest that the osteomalacia was due to hypophosphatemia caused by a renal leak. PTH is only contributory to the phosphaturia. Low calcitriol level contributes to the osteomalacia directly and indirectly through impaired mineral absorption and, therefore, is also responsible for the hypocalciuria. PMID- 3346152 TI - Black thyroid associated with minocycline therapy: histochemical and ultrastructural studies on the brown pigment. AB - The brown pigment found in the black thyroid, associated with minocycline therapy, was studied histochemically and ultrastructurally. The brown pigment was Fontana-Masson silver-positive, and was negative for iron, for autofluorescence under uv illumination, for periodic acid Schiff (PAS) and for acid-fast iodine peroxidase (AFIP) lipofuscin, and was bleached with potassium permanganate. The light and electron microscopic studies suggested that the pigment resembled melanin. Although the mechanism of the pigment deposition is not clear, a possible explanation may be that the pigment is related to direct oxidative degradation products of minocycline. PMID- 3346151 TI - Reduction or cessation of fetal movements after administration of steroids for enhancement of lung maturation. I. Clinical evaluation. AB - Changes in fetal activity ranging from reduction to cessation of fetal movements were observed in patients at the 25th to 34th week of gestation, who were receiving steroids for enhancement of fetal lung maturation. This was a transient phenomenon, and fetal movements returned to normal by 24 h after the last injection of steroids. Concomitantly, during the period of exposure to steroids, we found an increased incidence of nonreactive monitoring patterns on daily analysis of fetal heart monitoring tracing. Although the pathophysiology of these changes is still unclear, we believe that the practical value of this observation is of importance. Reduction or cessation of fetal movements and a nonreactive nonstress test are generally accepted signs of fetal compromise and considered as an indication for termination of pregnancy. In this selective group of patients this is a temporary phenomenon; therefore, conservative management would seem in order. PMID- 3346153 TI - Human orf in Israel. Report of three cases. AB - Orf, a viral disease of sheep and goats transmissible to man, is described in three patients living in Israeli cooperative settlements. Characteristically, the disease was manifested as a single, self-limited skin lesion in two of the patients, while in the third patient an unusual coexistence of orf and bullous pemphigoid was found. Not uncommonly, orf may be found in persons working with sheep and goats. Awareness of this disease by physicians may avoid unnecessary testing and treatments. PMID- 3346154 TI - Development of type II autoimmune polyglandular syndrome in a patient with idiopathic thrombocytopenic purpura. PMID- 3346155 TI - Attempts to predict the hemolytic potential of drugs in glucose-6-phosphate dehydrogenase deficiency of the Mediterranean type by an in vitro test. PMID- 3346156 TI - Monte Carlo calculations of doses to tiles irradiated by 60Co and 252Cf simulating atomic bomb gamma-ray fluences. AB - Dose calculations for tiles exposed to the Hiroshima atomic bomb radiations were undertaken. A Monte Carlo code, ABOMB, was developed which considers the characteristics of atomic bomb gamma-ray fluences and geometrical configurations. ABOMB was applied to tile dose calculations for the available photon sources with definite fluences. Its validity was tested by comparing the depth-dose curves calculated for 60Co and 252Cf beams with the equivalent experimental data obtained in the laboratory. Selection of parameters, contribution of backscattering, and computing time also were considered. Present calculations are considered to be accurate with uncertainties less than +/- 10%, and may be useful for correcting or reinforcing atomic bomb gamma-ray doses, together with tile dose measurements by thermoluminescent (TL) dosimetry. PMID- 3346157 TI - Medical x-ray exposure doses as contaminants of atomic bomb doses. AB - Since 1967 at the times of their biennial ABCC/RERF radiological examinations, all Adult Health Study (AHS) subjects have been interviewed to determine the exposures to medical x-rays they experienced in institutions other than RERF in order to estimate the numbers of examinations and corresponding doses which they received. These data have been stored on computer tapes together with the doses these subjects received during their radiological examinations in the ABCC/RERF Department of Radiology. Thus, their medical x-ray doses are available along with their atomic bomb doses (tentative 1965 doses revised, T65DR) for assessment of the role of ionizing radiation in the development of diseases. The medical x-ray doses incurred at RERF were assessed by means of phantom dosimetry. Those at other institutions were determined using phantom dosimetry data and results of surveys for trends in radiological examinations in Hiroshima and Nagasaki. By the end of 1982, the average medical x-ray doses to the active bone marrow were 12.04 mGy for A-bomb exposed groups and 8.92 mGy for control groups (not-in-cities); to the male gonads, 2.26 mGy and 1.89 mGy, respectively; and to the female gonads, 17.45 mGy and 12.58 mGy, respectively. Results for Hiroshima and Nagasaki were similar. The main impact of medical x-ray doses was in the lowest T65DR group. Medical x-ray active bone marrow doses ranged from 0.05-500% (mean, 35%) of A bomb doses in the 10-99 mGy T65DR group. In the 100-999 mGy T65DR group, medical x-ray active bone marrow doses ranged from 0.005-50% (mean, 5%) of their T65DR. In the greater than 1,000-mGy T65DR group, medical x-ray exposures were proportionally less. Female active bone marrow and gonad doses were similar in magnitude to the male active bone marrow doses. Medical x-ray exposures produced smaller doses to the gonads of males than to those of the females. The use of medical x-rays is steadily increasing. Careful consideration of doses from medical sources is essential for reliable assessments of the effects from exposures to the atomic bombs. PMID- 3346158 TI - Indoor concentrations of 220Rn and its decay products. AB - The distribution of 220Rn atoms in a room was derived from the diffusion equation. The activity concentrations of 212Pb and 212Bi were obtained in relation to 220Rn exhalation rate from a concrete wall. Near the surface of the concrete wall, the radiation exposure due to inhalation of 220Rn decay products may be significant in some cases. PMID- 3346159 TI - Population radiation absorbed dose from nuclear medicine procedures in The Netherlands. AB - The mean radiation absorbed dose per patient and for the whole population per caput per year in the Netherlands from diagnostic nuclear medicine procedures has been estimated using patient data from 10 large hospitals during either 1984 or 1985. The mean effective dose equivalent and the mean gonad dose equivalent per patient were 2.7 mSv and 1.7 mSv, respectively. Extrapolating these figures to all diagnostic nuclear medicine procedures in the Netherlands, the mean effective dose equivalent and the mean gonad dose equivalent per caput per year were 0.037 mSv and 0.024 mSv, respectively. PMID- 3346160 TI - The beagle: an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans. AB - The concentrations and the organ distribution patterns of 228Th, 230Th and 232Th in two 9-y-old dogs of our beagle colony were determined. The dogs were exposed only to background environmental levels of Th isotopes through ingestion (food and water) and inhalation as are humans. The organ distribution patterns of the isotopes in the beagles were compared to the organ distribution patterns in humans to determine if it is appropriate to extrapolate the beagle organ burden data to humans. Among soft tissues, only the lungs, lymph nodes, kidney and liver, and skeleton contained measurable amounts of Th isotopes. The organ distribution pattern of Th isotopes in humans and dog are similar, the majority of Th being in the skeleton of both species. The average skeletal concentrations of 228Th in dogs were 30 to 40 times higher than the average skeletal concentrations of the parent 232Th, whereas the concentration of 228Th in human skeleton was only four to five times higher than 232Th. This suggests that dogs have a higher intake of 228Ra through food than humans. There is a similar trend in the accumulations of 232Th, 230Th and 228Th in the lungs of dog and humans. The percentages of 232Th, 230Th and 228Th in human lungs are 26, 9.7 and 4.8, respectively, compared to 4.2, 2.6 and 0.48, respectively, in dog lungs. The larger percentages of Th isotopes in human lungs may be due simply to the longer life span of humans. If the burdens of Th isotopes in human lungs are normalized to an exposure time of 9.2 y (mean age of dogs at the time of sacrifice), the percent burden of 232Th, 230Th and 228Th in human lungs are estimated to be 3.6, 1.3 and 0.66, respectively. These results suggest that the beagle may be an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans. PMID- 3346161 TI - The effect of firing temperature on the lung retention and translocation of Pu following the inhalation of 238PuO2 and 239PuO2 by CBA/H mice. AB - Mice were exposed by inhalation to sized aerosols of 238PuO2 and 239PuO2 which had been fired at temperatures from 550-1250 degrees C and groups killed at times between 1 d and 2 y after exposure. Measurements were made of 238Pu and 239Pu in the lungs, lung-associated lymph nodes, liver and skeleton. With 239Pu, lung retention and translocation were independent of firing temperature. With 238Pu on the other hand, the retention in lung was greater initially than for 239Pu but, with the low-fired oxide, eventually fell below that of 239Pu. With high-fired oxides, the lung retention of 238Pu still exceeded that of 239Pu after 2 y. Translocation to liver and bone was invariably greater for 238Pu than for 239Pu and was also dependent on firing temperature. The practical implications of these findings are discussed. PMID- 3346162 TI - Absorption of 233U, 237Np, 238Pu, 241Am and 244Cm from the gastrointestinal tracts of rats fed an iron-deficient diet. AB - Absorption of U, Np, Am and Cm was increased by factors of 3.4, 7.1, 2.7 and 1.7, respectively, when nitrate solutions of these actinides were gavaged to adult rats fed an iron-deficient diet. Retention increased proportionately in liver, kidney and carcass. The concentration of the actinides excreted also increased substantially (over that of controls) in the urine of iron-deficient rats gavaged with 233U and 237Np, but not in those with 241Am or 244Cm. Weanling rats on an iron-deficient diet, gavaged with ferric nitrate immediately before administration of 238Pu nitrate, retained between 4% and 12% of the 238Pu retained by litter mates that were not treated intragastrically with iron. PMID- 3346163 TI - Interactions of 57Co, 85Sr and 137Cs with peat under acidic precipitation conditions. AB - Following the burial of low-level wastes in nuclear waste repositories, the interactions of radionuclides with surrounding soil infiltrated by acid precipitation could cause radionuclide migration and transport into nearby wells. To evaluate this migration through organically rich soil in the unsaturated zone, we measured sorption and desorption distribution ratios (Rd) of 57Co, 85Sr and 137Cs onto peat at pH 4. Peat samples rich in organic C showed relatively higher sorption Rd values for 57Co and 85Sr compared to soil samples with less organic C. The sorption and desorption Rd values for these radionuclides are similar, indicating the reversibility of the sorption process. The measurements suggest the importance of organic complexes for the retention of these radionuclides at the pH range (pH 4), where hydrolysis of the metals is not important and sorption is expected to be low. Cesium-137, on the other hand, appears to be associated more strongly with inorganic components of the soil samples, with its Rd value significantly higher in the peat material containing less organic C. The 137Cs desorption Rd on the same peat sample is also comparable to the sorption Rd indicating equilibrium. Both the organic and inorganic components of peat are thus able to retard the migration of radionuclides which may be found in nuclear waste repositories. The design of such a repository may be improved using a peat barrier to restrict radionuclide migration. PMID- 3346164 TI - Transfer of aged Pu to cattle grazing on a contaminated environment. AB - Estimates are obtained of the fraction of ingested or inhaled 239+240Pu transferred to blood and tissues of a reproducing herd of beef cattle, individuals of which grazed within fenced enclosures for up to 1064 d under natural conditions with no supplemental feeding at an arid site contaminated 16 y previously with Pu oxide. The estimated (geometric mean [GM]) fraction of Pu transferred from the gastrointestinal tract to blood serum was about 5 x 10(-6) (geometric standard error [GSE] = 1.4) with an approximate upper bound of about 2 x 10(-5). These results are in reasonable agreement with the value of 1 x 10(-5) recommended for human radiation protection purposes by the International Commission on Radiological Protection (ICRP) for insoluble Pu oxides that are free of very small particles. Also, results from a laboratory study by Stanley (St75), in which large doses of 238Pu were orally administered daily to dairy cattle for 19 consecutive days, suggest that aged 239+240Pu at this arid grazing site may not be more biologically available to blood serum than fresh 239+240Pu oxide. The estimated fractions of 239+240Pu transferred from blood serum to tissues of adult grazing cattle were: femur (3.2 X 10(-2), 1.8; GM, GSE), vertebra (1.4 X 10(-1), 1.6), liver (2.3 X 10(-1), 2.0), muscle (1.3 X 10(-1), 1.9), female gonads (7.9 X 10(-5), 1.5), and kidney (1.4 X 10(-3), 1.7). The blood-to-tissue fractional transfers for cattle initially exposed in utero were greater than those exposed only as adults by a factor of about 4 for femur (statistically significant) and of about 2 for other tissues (not significant). The estimated (GM) fraction of inhaled Pu initially deposited in the pulmonary lung was 0.34 (GSE = 1.3) for adults and 0.15 (GSE = 1.3) for cattle initially exposed in utero (a statistically significant difference), which may be compared with the expected fraction of 0.11 at the study site using the ICRP lung model for humans. PMID- 3346166 TI - Fitting parameters for medical diagnostic x-ray transmission data. PMID- 3346167 TI - A soft-tissue-substitute liquid. PMID- 3346165 TI - Evaluation of retinal exposures from repetitively pulsed and scanning lasers. AB - Threshold damage in the macaque retina is shown to be equivalent for the argon krypton (Ar-Kr) 647 nm and the helium-neon (He-Ne) 632.8-nm lines for exposures to continuous wave (CW) radiation from 1 to 1,000 s. This equivalence allows interpolation from experiments with 647-nm, exposures at power levels that are unavailable with the He-Ne laser. To simulate He-Ne laser scanner exposures, 40 microseconds pulses of 647-nm light transmitted through a revolving disk with holes in the periphery were used to expose the retinas of monkeys under deep anesthesia at pulse repetition frequencies (PRFs) of 100, 200, 400, and 1,600 Hz for exposure durations of 1, 10, 100, and 1,000 s. The thresholds between laser exposure at 488 nm (Ar-Kr) and between laser exposure at 647 nm (Kr) are compared to assess thermal versus photochemical effects on the retina. The threshold for 488-nm pulses was consistently lower than that for 647-nm pulses at all PRFs and exposure times. The difference in thresholds increased with exposure time and PRF. The sharp decreases in 488-nm thresholds at 100-s exposure times for each PRF can be interpreted as a basically photochemical effect. The radiant exposure required for damage at 647 nm was several orders of magnitude above the radiant exposure from typical He-Ne scanner applications. From the similarity of the macaque retina to the human retina, it is concluded that no realistic ocular hazard exists from exposure to scanning laser systems of 1 mW or less, operating at higher than 100 Hz. PMID- 3346168 TI - Proposed criteria to define Rn-prone areas from regional surveys. PMID- 3346170 TI - The four principles of external radiation protection: time, distance, shielding and decay. PMID- 3346169 TI - Comments on preventing use of 'E' notation in Health Physics submissions. PMID- 3346171 TI - Results of indoor Rn monitoring in Missouri. PMID- 3346172 TI - Variations in the intensity of psychiatric treatment across markets for mental health services in the United States. AB - Data are analyzed that describe the clinical work of 800 psychiatrists who practiced in one of 62 markets for mental health services in the United States during 1982 or 1983. Intensity of treatment (i.e., mean face-to-face treatment minutes per patient per month) ranges from a low of 107 minutes to a high of 368 minutes. Each of two multiple regression models accounts for 60 percent or more of the observed variation. Most of the variation in intensity of treatment can be accounted for with variables associated with the patient's severity or stage of illness and the type of treatment provided. Patients who fall on the midrange of the severity scale tend to consume the most treatment time per month. None of the economic variables were significant at any reasonable level. These findings have immediate implications for the development of more functional prospective payment systems for the financing of mental health care and for the longer-term debate over the nature of mental health services markets. PMID- 3346174 TI - Periodic acid Schiff--p phenylenediamine staining of glycogen in chondrocytes. A new combination which improves both cellular detail and glycogen identification. AB - This study reports a method whereby glycogen is identified in the chondrocytes of the secondary center of ossification prior to mineralization. The use of new fuchsin rather than basic fuchsin on one micron Spurr sections of femoral head cartilage fixed with potassium ferrocyanide-reduced osmium produced excellent identification of glycogen and when followed by p phenylenediamine, intensified cellular detail. PMID- 3346173 TI - Monoclonal antibodies against calcitonin. Characterization and application in light and electron microscopy immunocytochemistry. AB - Twenty-seven monoclonal antibodies (MAbs) to synthetic human calcitonin (CT) were characterized for their reactivities with human CT peptide fragments by dot-blot analysis on nitrocellulose paper. Most of the antibodies bound to the C-terminus and fewer to the mid-region of CT. We have studied thyroid tissue specimens from several animal species after fixation in paraformaldehyde-, glutaraldehyde- or picric acid-containing mixtures and cryostat sectioning or embedment in paraffin or plastic (Epon 812 or Lowicryl 4KM) using this panel of MAbs. The site of antigen-antibody reaction was revealed either by immunoperoxidase, immunoalkaline phosphatase or by silver-enhanced immunogold staining methods. All MAbs were able to localize CT in human, rat and mouse thyroid C cells. Nineteen MAbs recognizing synthetic salmon CT and synthetic [Asu1,7]-eel CT by dot-blot, reacted with chicken ultimobranchial body C cells. One MAb recognizing native porcine CT by dot-blot, stained C cells in hog thyroid. Immunopositivity was confined to the cytoplasm and ultrastructural immunogold labelling demonstrated that cytoplasmic secretory granules were stained. Surgical specimens from human medullary thyroid carcinoma were also analysed for the presence of CT and a variable number of positive cells was found. Furthermore, Congo red-positive areas were shown to react with the MAbs. All conventional staining and immunoabsorption controls were negative. Hence, these MAbs may be suitable for use in routine immunopathological diagnosis of CT-producing tumors and for immunocytochemical localization of the three major CT variants in different animal species. PMID- 3346176 TI - Binding and internalization in vivo of [125I]hCG in Leydig cells of the rat. AB - The present study was performed to demonstrate the binding, mode of uptake, pathway and fate of iodinated human chorionic gonadotropin ([125I]hCG) by Leydig cells in vivo using electron microscope radioautography. Following a single injection of [125I]hCG into the interstitial space of the testis, the animals were fixed by perfusion with glutaraldehyde at 20 minutes, 1, 3, 6 and 24 hours. The electron microscope radioautographs demonstrated a prominent and qualitatively similar binding of the labeled hCG on the microvillar processes of the Leydig cells at 20 minutes, 1, 3, and 6 hours. The specificity of the [125I]hCG binding was determined by injecting a 100-fold excess of unlabeled hormone concurrently with the labeled hormone. Under these conditions, the surface, including the microvillar processes of Leydig cells, was virtually unlabeled, indicating that the binding was specific and receptor-mediated. In animals injected with labeled hCG and sacrificed 20 minutes later, silver grains were also seen overlying the limiting membrane of large, uncoated surface invaginations and large subsurface vacuoles with an electron-lucent content referred to as endosomes. A radioautographic reaction was also seen within multivesicular bodies with a pale stained matrix. At 1 hour, silver grains appeared over dense multivesicular bodies and occasionally over secondary lysosomes, in addition to the structures mentioned above, while at 3 and 6 hours, an increasing number of secondary lysosomes became labeled. At 24 hours, binding of [125I]hCG to the microvillar processes of Leydig cells persisted but was diminished, although a few endosomes, multivesicular bodies and secondary lysosomes still showed a radioautographic reaction. No membranous tubules that were seen in close proximity to, or in continuity with, endosomes and multivesicular bodies were observed to be labeled at any time interval. Likewise, an attempt to correlate silver grains with small coated or uncoated pits, the stacks of saccules of the Golgi apparatus and other Golgi-related elements including GERL, proved unsuccessful, since these structures were mostly unlabeled. These in vivo experiments thus demonstrate the specific binding of [125I]hCG to the plasma membrane of Leydig cells predominantly on their microvillar processes, and the subsequent internalization of the labeled hCG to secondary lysosomes. In addition, binding and internalization of hCG persisted for long periods of time. PMID- 3346175 TI - Light and electron microscopic demonstration of phospholipase B activity in the mouse eosinophil. AB - Phospholipase B (EC 3.1.1.5) which hydrolyzes phospholipids in the alpha and beta positions was demonstrated in murine leukocytes using light and electron microscopic histochemical techniques. Leukocytes (neutrophils, lymphocytes, macrophages, eosinophils) were harvested from peritoneal exudates of mice. Cells were fixed in 4% calcium-formol fixative for 10 min at 4 degrees C for light microscopy and 30 min at room temperature for electron microscopy, after which they were incubated at 37 degrees C in medium at pH 6.6 containing 2 microM lysolecithin and CaCl2. The fatty acids released during the hydrolytic reaction were trapped as a calcium precipitate and were converted to a cobalt precipitate for light microscopy by treatment with cobalt acetate or to a lead precipitate for electron microscopy by treatment with lead nitrate. The reaction products were observed to be present in eosinophils and absent in neutrophils, lymphocytes and macrophages. It is concluded that the eosinophilic leukocyte is the carrier cell for phospholipase B in inflammatory reactions. PMID- 3346177 TI - Morphologic changes induced by short-term ischemia in the rat testis are not affected by treatment with superoxide dismutase and catalase. AB - Short-term testicular ischemia was induced unilaterally by ligating the testicular artery for 60 or 100 minutes in adult rats. After 7 days, the rats were fixed by vascular perfusion. The effect of ischemia and reperfusion was quantified using morphometric techniques. Occlusion of the testicular artery for 60 and 100 minutes resulted in a mild and moderate damage, respectively, to the seminiferous tubules. The contralateral control testis was not affected. To study the role of oxygen radicals in ischemia-reperfusion-induced testicular damage, rats were treated with superoxide dismutase and catalase. These radical scavengers did not influence the extent of testicular damage. PMID- 3346178 TI - Influence of photoperiod, ambient temperature and melatonin on testosterone synthesis and release during reproductive maturation in male deer mice. AB - Four experiments were designed to investigate the influence of photoperiod and other environmental factors on androgen production and reproductive maturation in deer mice. Male prairie deer mice (Peromyscus maniculatus), born in a light/dark cycle of 6L:18D, either remained in this short photoperiod or were switched to a long day regimen of 16L:8D at weaning. In a cross-sectional experiment, the deer mice were killed between 3 and 8 weeks of age for measurement of serum testosterone concentration and reproductive organ weights. In a second experiment, blood was collected from each mouse at weekly intervals between 3 and 9 weeks of age. This repeated measures design was used to reduce the high variability in testosterone values observed in the first experiment. Reproductive organs were weighed at the termination of the experiment. Testosterone concentrations and reproductive organ weights were greater in males reared in the long photoperiod in both experiments. In a third experiment, the animals were housed under five different conditions to test the influence of high ambient temperature and melatonin as well as photoperiod. At 7 weeks of age, they received an injection of hCG or saline. More testosterone was released in deer mice reared in 16L:8D and 27 C than in those reared in short days (6L:18D) or those reared in high ambient temperature (35 C) or those treated with exogenous melatonin. One week later, animals were sacrificed. The single hCG treatment caused significant reversal of the suppression of accessory sex organ weights following melatonin, short days or 35 C temperature. In a fourth experiment, the additive influence of melatonin and 35 C temperature was tested. Animals treated with 35 C or both melatonin and 35 C had lower serum testosterone at 7 weeks of age, released less testosterone after hCG, and had smaller organ weights with or without hCG than long day controls. The influence of melatonin treatment and 35 C temperature appears to be additive for testicular weight and testosterone release after hCG. Thus, the attenuation of reproductive development that accompanied short days, melatonin treatment and high ambient temperature occurred via diminished testosterone secretion, which can be overcome at least in part by gonadotropin treatment. PMID- 3346179 TI - Relationships between computerized measurements of motion of frozen-thawed bull spermatozoa and fertility. AB - A computerized system (CellSoft, CRYO Resources, Ltd.) was validated using video tapes of frozen-thawed bull spermatozoa diluted in filtered (0.2 micron) egg yolk citrate extender (8 X 10(6) spermatozoa/ml) and analyzed at 30 frames/sec for the percentage of motile spermatozoa (greater than or equal to 20 microns/sec) and linear velocity of motile spermatozoa. Virtually all motile spermatozoa were detected and debris rarely were classified as immotile spermatozoa if the extender had been filtered. Variation about the mean for percent motile cells was similar when only 12 rather than 20 or 30 frames/field were analyzed. Use of 20 frames/field was adequate to determine the percentage of motile bull spermatozoa. Five mixtures of live and killed spermatozoa were analyzed (four bulls) to evaluate accuracy. Percent motile spermatozoa was correlated (r = 0.97) with the ratio of live:killed spermatozoa. Mean linear velocity of motile spermatozoa was similar for each mixture (P greater than 0.05). To further evaluate accuracy, percent motile spermatozoa was determined by computer and by "track motility" (20 samples; 0 to 63% motile spermatozoa); values were correlated (r = 0.95). The system was precise (CV of 6% based on triplicate analyses of the same samples) and reasonably accurate for evaluating bull sperm motility if the extender had been filtered and 20 to 25 fields (greater than or equal to 200 spermatozoa) were evaluated. Correlations between measurements of sperm motion and fertility were studied using cryopreserved semen from two fertility trials. For the first, 75 day nonreturn rate data for 20 samples of bull semen (10 bulls) were not significantly correlated with evaluations made by CellSoft. For the second fertility trial, the competitive fertility index (a measure of relative fertility) for nine bulls was correlated (r greater than or equal to 0.68; P less than 0.05) with percent motile spermatozoa, linear velocity and straight-line velocity. Multiple correlations based on six characteristics evaluated by CellSoft, at 0 or 1.5 hours, and the competitive fertility index were greater than or equal to 0.94. Based on the latter data, the system may facilitate prediction of the relative fertility of bull spermatozoa. PMID- 3346180 TI - Serum testosterone response to desialylated human choriogonadotropin in man. AB - To assess the in vivo steroidogenic activity of desialylated human choriogonadotropin (hCG) in man, highly purified desialylated hCG was administered as a constant intravenous infusion over 6 hours to four normal men at a rate sufficient to maintain substantial levels of desialylated hCG in the serum. The mean percent change of serum testosterone from baseline during the first 6 hours in men given an infusion of desialylated hCG was compared to that in saline-infused controls and that in men given highly purified intact hCG. The mean change of serum testosterone at 6 hours in the group infused with desialylated hCG (129% of baseline) was significantly greater than that of the controls (69% of baseline). Furthermore, the response to desialylated hCG could not be distinguished from that of hCG (125% of baseline). It was concluded that desialylated hCG, when given as a constant intravenous infusion, can elicit a substantial serum testosterone response comparable to that seen with purified hCG, and thus, that desialylated hCG behaves as an agonist of the LH/CG receptors on human Leydig cells. PMID- 3346181 TI - MM 42842, a new member of the monobactam family produced by Pseudomonas cocovenenans. I. Identification of the producing organism. AB - A bacterial soil isolate designated 326-32B produces a new member of the monobactam series of antibiotics, MM 42842, and the bulgecins. Identification studies show isolate 326-32B to be a strain of Pseudomonas cocoveneans which is a species previously noted for the production of toxoflavin. A description of P. cocovenenans does not appear to have been previously published and the identify of strain 326-32B was established by means of a direct comparison with the deposited organism P. cocovenenans NCIB 9450. The properties of strain 326-32B, and P. cocovenenans NCIB 9450 were compared with those of the monobactam and bulgecin producing organisms Pseudomonas acidophila ATCC 31363 and Pseudomonas mesoacidophila ATCC 31433. The four organisms were found to share certain properties, including the ability to grow at pH 4.0. PMID- 3346182 TI - Sch 36605, structure of a novel nucleoside. PMID- 3346183 TI - Urdamycins, new angucycline antibiotics from Streptomyces fradiae. III. The structures of urdamycins C and D. PMID- 3346184 TI - Sch 37137, a novel antifungal compound produced by a Micromonospora sp. Taxonomy, fermentation, isolation, structure and biological properties. AB - A new antifungal compound, Sch 37137, was isolated from the cultured broth of a Micromonospora sp., SCC 1792. Sch 37137 is structurally related to A 19009, a dipeptide previously discovered from a Streptomyces sp. The compound was weakly active against species of Candida and dermatophytes (mean MICs greater than or equal to 128 micrograms/ml) in Sabouraud dextrose, yeast-nitrogen and modified Eagles minimum essential media; however activity against Candida sp. (mean MICs greater than or equal to 12 micrograms/ml) and dermatophytes (mean MICs greater than or equal to 0.8 microgram/ml) significantly improved in MA medium. PMID- 3346185 TI - The X-ray crystal structure of pentalenolactone F methyl ester (epi pentalenolactone F). PMID- 3346186 TI - Studies on the bioavailability of some new erythromycin esters. PMID- 3346187 TI - Involvement of cell impermeability in resistance to macrolides in some producer streptomycetes. PMID- 3346188 TI - Assessment of the anti-diabetic activity of deoxyspergualin in low-dose streptozotocin-induced diabetic mice. PMID- 3346189 TI - Sch 36605, a novel anti-inflammatory compound. Taxonomy, fermentation, isolation and biological properties. AB - A novel anti-inflammatory compound, Sch 36605, belonging to the blasticidin family of nucleoside compounds was isolated from the fermentation filtrate of a Streptomyces sp. Sch 36605, as well as blasticidin S, demonstrated anti inflammatory activity in the reverse passive Arthus reaction and the adjuvant arthritic rat at doses ranging between 1-10 mg/kg and 0.3-6.0 mg/kg, respectively. A minor component, Sch 366606, co-produced in the in the fermentation was isolated and identified as a known compound in the blasticidin family of compounds. PMID- 3346190 TI - Vinigrol, a novel antihypertensive and platelet aggregation inhibitory agent produced by a fungus, Virgaria nigra. I. Taxonomy, fermentation, isolation, physicochemical and biological properties. AB - Vinigrol, produced by a fungal strain identified as Virgaria nigra, was extracted from the cultured mycelium, purified by solvent extraction followed by chromatography on silica gel and then isolated as crystals (C20H34O3, mp 108 degrees C). Vinigrol decreased arterial blood pressure of anesthetized normotensive rats dose-dependently when administered intravenously. Vinigrol inhibited platelet activating factor and epinephrine induced platelet aggregation. PMID- 3346191 TI - Tirandalydigin, a novel tetramic acid of the tirandamycin-streptolydigin type. II. Isolation and structural characterization. AB - Tirandalydigin a structurally unique hybrid of the tirandamycin-streptolydigin families of tetramic acid antibiotics has been isolated from the fermentation beers of Streptomyces sp. AB-1006A-9. The structure of this anti-anaerobic antibiotic has been characterized based upon NMR, UV and mass spectrometric data. PMID- 3346192 TI - New aureolic acid antibiotics. I. Screening, isolation, characterization and biological properties. AB - A new antibiotic complex was isolated from the fermentation broth of Streptomyces aburaviensis PA-39856. The individual factors, demethylolivomycins A, B and demethylchromomycins A2, A3 were separated and purified by preparative HLC. These antibiotics possess high activities against Gram-positive bacteria and P388 leukemia in mice. PMID- 3346193 TI - NMR studies of chromomycins, olivomycins, and their derivatives. AB - Detailed studies on the 13C and 1H NMR spectra of chromomycins A2 and A3, olivomycins A and B, and their derivatives clarified the assignment of many signals which had been unassigned or erroneously reported in the literatures. The revised assignments for chromomycin A3 and olivomycin A include the assignment of a key 13C signal used to discuss the saccharide linkage in question. Structure analyses based on the revised assignments support the alpha,1----3-bond between components of the disaccharide moiety in the molecules. Some general information useful for structure analysis of saccharides is also reported. PMID- 3346194 TI - New aureolic acid antibiotics. II. Structure determination. AB - Structure determination using NMR spectroscopy of new aureolic acid analogues, demethylchromomycins A2 and A3 and demethylolivomycins A and B produced by Streptomyces aburaviensis PA-39856, is described. PMID- 3346195 TI - MM 42842, a new member of the monobactam family produced by Pseudomonas cocovenenans. II. Production, isolation and properties of MM 42842. AB - A new member of the monobactam family of beta-lactam antibiotics, designated MM 42842, has been detected in a culture of Pseudomonas cocovenenans. The production, isolation and some properties of the antibiotic are described. Structural studies show MM 42842 to be closely related to the previously described antibiotic sulfazecin. PMID- 3346196 TI - The jitteriness syndrome in panic disorder patients treated with antidepressants. AB - The jitteriness syndrome (jitteriness, shakiness, increased anxiety, and insomnia) can develop with low doses of tricyclic antidepressants in patients who are sensitive to these drugs. The authors review the antidepressant treatment of 180 patients. Only those with panic attacks had jitteriness, usually during the first week of treatment. Desipramine was associated with a much higher frequency of jitteriness than was imipramine. Tolerance to jitteriness occurred with continued treatment, but fewer patients with jitteriness responded to treatment, apparently because of difficulties in increasing the dose. Characteristics of the jitteriness syndrome in panic disorder patients are consistent with noradrenergic hypotheses of panic anxiety. The clinical and theoretical implications of these findings are discussed. PMID- 3346197 TI - Effect of pindolol administration on serum levels of thioridazine, haloperidol, phenytoin, and phenobarbital. AB - Twenty-six male patients with intermittent explosive disorder secondary to organic brain disease were studied. Each had been treated with long-term administration of thioridazine, haloperidol, phenytoin, and/or phenobarbital, either singly or in combination. The effect of adding increasing doses of pindolol--a beta-adrenergic blocking agent previously demonstrated to be effective in the treatment of intermittent explosive disorder--on serum levels of each long-term medication was determined. Moderate, dose-related increases in serum levels of thioridazine and two of its metabolites were found when pindolol was added. Conversely, higher-than-expected serum pindolol levels occurred in patients receiving thioridazine. No serum level increases were found for haloperidol, phenytoin, or phenobarbital when pindolol was added to each of these drugs individually, but serum phenytoin levels did rise in two patients receiving all three drugs simultaneously when pindolol was added. Three treatment failures with pindolol occurred in association with low serum pindolol levels. PMID- 3346198 TI - Brain structure and function in sexual molesters of children and adolescents. AB - Sixteen men incarcerated in a state psychiatric facility pursuant to sexual molestation of children and/or adolescents were evaluated by computed tomography (CT) head scans and regional cerebral blood flow (rCBF) estimation. Compared with controls, child molesters were found to have thinner and less dense skulls and lower rCBF values. Variations from control values in rCBF and characteristics of CT head scans for the sex offenders suggest a role for cerebral dysfunction in the etiology of their aberrant behavior. PMID- 3346199 TI - Antiaggressive effect of adjunctive clonazepam in schizophrenia associated with seizure disorder. AB - A case of schizophrenia associated with complex partial seizure disorder and postictal violence, both refractory to conventional treatment, is presented. Adjunctive treatment with clonazepam resulted in the cessation of the seizures and of persistent, violent hallucinations. The theoretical implications for possible mechanisms underlying at least some types of aggressive behavior are discussed. PMID- 3346200 TI - A maniclike illness associated with right frontal arteriovenous malformation. AB - Secondary mania may be caused by metabolic derangements, intoxications, and/or structural lesions, as well as by epilepsy. The authors describe a maniclike illness in a 16-year-old girl in whom a right frontal arteriovenous malformation was discovered. The most effective medical therapy was a combination of lithium and carbamazepine. Ultimately, the malformation was resected, and since then the patient has done well without medication. The possibility is raised that mania may be the presenting syndrome of a seizure disorder that is secondary to an organic lesion. PMID- 3346201 TI - Catatonia as a manifestation of paraneoplastic encephalopathy. AB - The psychopathological, electrophysiological, and pathological features of a 58 year-old woman suffering from anaplastic lung carcinoma with paraneoplastic encephalopathy are presented. The predominant behavioral manifestation was a catatonic syndrome that was partially responsive to clonazepam. Although a variety of neurological, psychiatric, and other causes of catatonia have been reported, this is the first reported case of catatonia caused by paraneoplastic encephalopathy. PMID- 3346202 TI - Excess suicide among formerly hospitalized child psychiatry patients. AB - The authors report suicide risk among 1331 child psychiatry inpatients followed up for 4 to 15 years in a record-linkage study. Age- and sex-matched comparisons were made with the general population of Iowa (the state from which most of the subjects were selected). Suicide rates were higher than expected for both sexes, but the excess (9 suicides) was significant only for males. No suicides occurred earlier than age 17. The risk of suicide was 80 times that expected for schizophrenic patients and 25 times that expected for patients with organic mental disorders. Unlike follow-up studies of adult inpatients, a significant excess of suicide was not associated with affective disorder, substance abuse, neurosis, or anorexia nervosa. Clinical variables indicating more complicated psychiatric disturbance were associated with an even greater rate of suicide; these variables included multiple hospitalizations, a hospital stay of more than 15 days, and the presence of a medical diagnosis. PMID- 3346203 TI - The dexamethasone suppression test in bulimia: nonsuppression associated with depression and suboptimal weight. AB - This study was designed to assess the extent to which DST nonsuppression in bulimic women could be predicted by the incidence of major depression in the patient and her family and by other factors known to affect DST results, such as suboptimal weight. The DST was administered to 33 women who met DSM-III criteria for bulimia. Subjects were given a complete psychiatric and psychological assessment, including the National Institute of Mental Health Diagnostic Interview Schedule, a personal and family medical history questionnaire, the Hopkins SCL-90, and the Eating Disorders Inventory. Ideal weight was determined with Metropolitan Life tables. The rate of DST nonsuppression was 58%. Nonsuppression was more frequent among women who suffered from major depression and those who maintained a suboptimal weight. Depression and suboptimal weight were unrelated and thus appear to contribute independently to the high rate of DST abnormalities commonly seen in bulimia. PMID- 3346204 TI - Psychotic and nonpsychotic depression: comparison of response to ECT. AB - The charts of 46 patients who underwent ECT in a teaching hospital between 1980 and 1986 were reviewed. All patients were suffering from major depression, with or without psychotic features, and were resistant to pharmacotherapy. Response to ECT was compared between those with psychotic features (N = 27) and those without psychotic features (N = 19). Both groups had equal and effective response to ECT. Therefore, the presence of psychotic features was not significant in predicting response to ECT. PMID- 3346205 TI - ATP formation onset lag and post-illumination phosphorylation initiated with single-turnover flashes. II. Two modes of post-illumination phosphorylation driven by either delocalized or localized proton gradient coupling. AB - Two modes of chloroplast membrane post-illumination phosphorylation were detected, using the luciferin-luciferase ATP assay, one of which was not influenced by added permeable buffer (pyridine). That finding provides a powerful new tool for studying proton-membrane interactions during energy coupling. When ADP and Pi were added to the thylakoid suspension after a train of flashes [similar to the traditional post-illumination phosphorylation protocol (termed PIP- here)], the post-illumination ATP yield was influenced by pyridine as expected, in a manner consistent with the ATP formation, in part, being driven by protons present in the bulk inner aqueous phase, i.e., through a delocalized protonmotive force. However, when ADP and Pi were present during the flash train (referred to as PIP+), and ATP formation occurred during the flash train, the post-illumination ATP yield was unaffected by the presence of pyridine, consistent with the hypothesis that localized proton gradients were driving ATP formation. To test this hypothesis further, the pH and flash number dependence of the PIP- and PIP+ ATP yields were measured, the results being consistent with the above hypothesis of dual compartment origins of protons driving post-illumination ATP formation. Measuring proton accumulation during the attainment of the threshold energization level when no delta psi component was allowed to form (+ valinomycin, K+), and testing for pyridine effects on the proton uptake, reveals that the onset of ATP formation requires the accumulation of about 60 nmol H+ (mg Chl)-1. Between that level and about 110-150 nmol H+ (mg Chl)-1, the accumulation appears to be absorbed by localized-domain membrane buffering groups, the protons of which do not equilibrate readily with the inner aqueous (lumen) phase. Post illumination phosphorylation driven by the dissipation of the domain protons was not affected by pyridine (present in the lumen), even though the effective pH in the domains must have been well into the buffering range of the pyridine. That finding provides additional insight into the localized domains, namely that protons can be absorbed by endogenous low pK buffering groups, and released at a low enough pH (less than or equal to 5.7 when the external pH was 8, less than or equal to 4.7 at pH 7 external) to drive significant ATP formation when no further proton production occurs due to the redox turnovers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346206 TI - ATP formation onset lag and post-illumination phosphorylation initiated with single-turnover flashes. III. Characterization of the ATP formation onset lag and post-illumination phosphorylation for thylakoids exhibiting localized or bulk phase delocalized energy coupling. AB - When 100 mM KCl replaced sucrose in a chloroplast thylakoid stock suspension buffer, the membranes were converted from a localized proton gradient to a delocalized proton gradient energy coupling mode. The KCl-suspended but not the sucrose-suspended thylakoids showed pyridine-dependent extensions of the ATP onset lag and pyridine effects on post-illumination phosphorylation. The ATP formation assays were performed in a medium of identical composition, using about a 200-fold dilution of the stock thylakoid suspension; hence the different responses were due to the pretreatment, and not the conditions present in the phosphorylation assay. Such permeable buffer effects on ATP formation provide a clear indicator of delocalized proton gradients as the driving force for phosphorylation. The pyridine-dependent increases in the onset lags (and effects on post-illumination phosphorylation) were not due to different ionic conductivities of the membranes (measured by the 515 nm electrochromic absorption change), H+/e- ratios, or electron transport capacities for the two thylakoid preparations. Thylakoid volumes and [14C]pyridine equilibration were similar with both preparations. The KCl-induced shift toward a bulk-phase delocalized energy coupling mode was reversed when the thylakoids were placed back in a low-salt medium. Proton uptake, at the ATP-formation energization threshold flash number, was much larger in the KCl-treated thylakoids and they also had a longer ATP formation onset lag, when no pyridine was present. These results are consistent with the salt treatment exposing additional endogenous buffering groups for interaction with the proton gradient. The concomitant appearance of the pyridine buffer effects implies that the additional endogenous buffering groups must be located on proteins directly exposed in the aqueous lumen phase. Kinetic analysis of the decay of the post-illumination phosphorylation in the two thylakoid preparations showed different apparent first-order rate constants, consistent with there being two different compartments contributing to the proton reservoirs that energize ATP formation. We suggest that the two compartments are a membrane phase localized compartment operative in the sucrose-treated thylakoids and the bulk lumen phase into which protons readily equilibrate in the KCl-treated thylakoids. PMID- 3346208 TI - Retinol-regulated gene expression in human tracheobronchial epithelial cells. Enhanced expression of elongation factor EF-1 alpha. AB - Conducting airway epithelial cells requires vitamin A or its synthetic chemicals (retinoids) for their survival and for the expression of normal mucociliary functions. By using molecular cloning, we have shown that one of the effects of retinol on cultured human tracheobronchial epithelial (HTBE) cells is the enhancement (from 2- to 4-fold) of the mRNA encoding the elongation factor EF-1 alpha. Sequence analysis has shown that clone HT7, which was identified by differential hybridization procedures, contained a cDNA insert which encoded a protein closely resembling (81%) elongation factor EF-1 alpha from brine shrimp and completely identical to the published sequence of human elongation factor EF 1 alpha (Brands, H.H.G.M., Maassen, J.A., Van Hemert, F.J., Amons, R., and Moller, W. (1986) Eur. J. Biochem. 155, 167-171). Regions of homology of HT7 to EF-Tu from yeast mitochondria, plant chloroplasts, and Escherichia coli are also evident. A single RNA band at 1700 bases was observed for both untreated and retinol-treated HTBE cells, and for mouse liver and parotid glands when Northern transfer from denaturing agarose gel was probed with a 32P-labeled HT7 insert. An enhanced amino acid incorporation and increased protein content per cell for HTBE cells grown in the presence of retinol were observed. Results presented by these studies indicate that retinol may regulate the transcription of a factor required for translation. PMID- 3346207 TI - ATP formation onset lag and post-illumination phosphorylation initiated with single-turnover flashes. I. An assay using luciferin-luciferase luminescence. AB - The great sensitivity of the luciferin-luciferase ATP detection system allows direct observation of ATP formation derived from single-turnover flashes in a thylakoid reaction mixture. The method can measure the energization threshold- the number of flashes required for the initiation of ATP formation--as well as detect post-illumination ATP formation after the last flash of a flash sequence. We describe the characteristics of this post-illumination phosphorylation which can be observed after a series of phosphorylating flashes (PIP+) or when the assay for ATP formation was performed in a "traditional" manner where the ADP and Pi were added after the flash-energization period (PIP-). Comparing PIP+ yields and kinetics of the PIP+ decay under various treatments can give information about membrane energization events only if it is clearly established that different PIP+ yields and decay rates are not due to limitations of the luciferase-catalyzed reaction. Experiments showing that the PIP+ ATP yield and kinetics were due to membrane-limited deenergization events (proton efflux) rather than luciferase limitations include: (1) An uncoupler, nigericin, added after the last flash reduced the PIP+ yield, but had no effect on the luciferase reaction. (2) The kinetics of the luminescence after adding standard ATP were much faster than the PIP+ kinetics. (3) Valinomycin and K+ stimulated the PIP+ yield but had no influence on the luciferase reaction. (4) Lowering the pH from 8 to 7 increased both the PIP- (an assay independent of luciferase kinetics) and the PIP+ ATP yields, an expected result owing to the greater endogenous buffering power encountered by the proton gradient when the external pH is 7. In spite of the last-mentioned point, the threshold flash number for ATP formation onset was the same for pH 7 and 8 (valinomycin, K+ present) at slow flash frequencies. This is consistent with a membrane-localized rather than a delocalized gradient. The accompanying reports (W. A. Beard, G. Chiang and R. A. Dilley, and W. A. Beard and R. A. Dilley, J. Bioenerg. Biomembr.) show that different conditions can lead to observing either localized or delocalized proton gradient coupling in the PIP+ event and the ATP onset threshold flash number. PMID- 3346209 TI - Mitochondrial calcium release as induced by Hg2+. AB - Addition of Hg2+ to mitochondria of rat kidney induces efflux of intramitochondrial Ca2+. This reaction is accompanied by a diminution of the NAD(P)H/NAD(P) ratio and a decrease of the internal negative membrane potential. These effects were enhanced by dithiothreitol. The binding of mercuric ions to mitochondria saturates with a maximal binding of 9 nmol min-1 mg-1. The stoichiometry between Ca2+ released and Hg2+ bound showed that in the presence of dithiothreitol, the binding of approximately 1 nmol of Hg2+/mg of protein suffices to induce the release of the accumulated Ca2+. In the electrophoretic analysis of Hg-labeled mitochondrial proteins it was found that 203Hg2+ bound mainly to proteins that have molecular masses of 20 and 30 kDa. It is proposed that Hg2+-induced Ca2+ release is due to modification of--SH groups of these latter proteins. PMID- 3346210 TI - Alteration of epidermal growth factor receptor activity by mutation of its primary carboxyl-terminal site of tyrosine self-phosphorylation. AB - The epidermal growth factor (EGF) receptor, which exhibits intrinsic protein tyrosine kinase activity, undergoes a rapid, intramolecular self-phosphorylation reaction following EGF activation. The primary sites of tyrosine self phosphorylation in vivo are located in the extreme carboxyl-terminal region of the molecule, principally Tyr-1173. To test the biological and biochemical consequences of this EGF receptor self-phosphorylation, we made the mutation Tyr- --Phe-1173. Membranes containing the mutated receptor exhibited an ED50 for EGF activation of tyrosine kinase activity equivalent to control receptor at both high and low substrate levels, but exhibited reduced basal and EGF-stimulated tyrosine kinase activity at low, non-saturating substrate levels. The Tyr----Phe 1173 mutant possessed high affinity EGF binding and could still self phosphorylate other tyrosine sites in an intramolecular fashion with a low Km for ATP (200 nM), suggesting that this alteration did not grossly change receptor structure. When EGF-dependent growth of Chinese hamster ovary cells expressing comparable levels of control or mutant EGF receptor was measured, the ability of the mutant receptor to mediate cell growth in response to EGF was reduced by approximately 50%, yet both receptors exhibited a similar affinity and ED50 for EGF. These results support the concept that this self-phosphorylation site can act as a competitive/alternate substrate for the EGF receptor, and that this region of the molecule is important in modulating its maximal biological activity. PMID- 3346211 TI - Role of mitochondrial transamination in branched chain amino acid metabolism. AB - Oxidative decarboxylation and transamination of 1-14C-branched chain amino and alpha-keto acids were examined in mitochondria isolated from rat heart. Transamination was inhibited by aminooxyacetate, but not by L-cycloserine. At equimolar concentrations of alpha-ketoiso[1-14C]valerate (KIV) and isoleucine, transamination was increased by disrupting the mitochondria with detergent which suggests transport may be one factor affecting the rate of transamination. Next, the subcellular distribution of the aminotransferase(s) was determined. Branched chain aminotransferase activity was measured using two concentrations of isoleucine as amino donor and [1-14C]KIV as amino acceptor. The data show that branched chain aminotransferase activity is located exclusively in the mitochondria in rat heart. Metabolism of extramitochondrial branched chain alpha keto acids was examined using 20 microM [1-14C]KIV and alpha-ketoiso[1 14C]caproate (KIC). There was rapid uptake and oxidation of labeled branched chain alpha-keto acid, and, regardless of the experimental condition, greater than 90% of the labeled keto acid substrate was metabolized during the 20-min incubation. When a branched chain amino acid (200 microM) or glutamate (5 mM) was present, 30-40% of the labeled keto acid was transaminated while the remainder was oxidized. Provision of an alternate amino acceptor in the form of alpha-keto glutarate (0.5 mM) decreased transamination of the labeled KIV or KIC and increased oxidation. Metabolism of intramitochondrially generated branched chain alpha-keto acids was studied using [1-14C]leucine and [1-14C]valine. Essentially all of the labeled branched chain alpha-keto acid produced by transamination of [1-14C]leucine or [1-14C]valine with a low concentration of unlabeled branched chain alpha-keto acid (20 microM) was oxidized. Further addition of alpha ketoglutarate resulted in a significant increase in the rate of labeled leucine or valine transamination, but again most of the labeled keto acid product was oxidized. Thus, catabolism of branched chain amino acids will be favored by a high concentration of mitochondrial alpha-ketoglutarate and low intramitochondrial glutamate. PMID- 3346212 TI - Correlated metabolism of proteoglycans and hyaluronic acid in bovine cartilage organ cultures. AB - Proteoglycans exist in cartilage as complexes in which many proteoglycan molecules are bound to a central filament of hyaluronic acid. Many studies have investigated changes taking place in proteoglycan monomer structure during cartilage catabolism usually under the assumption that hyaluronic acid is a relatively inert metabolic component of the complex. In this paper we present organ culture data supporting a new hypothesis that the catabolism of proteoglycans and hyaluronic acid are coordinately regulated by chondrocytes. The data indicates that: 1) newly synthesized hyaluronate and proteoglycan maintain a nearly constant ratio, almost identical to that existing for the total chemical amounts of these two components in cartilage tissue; 2) these two components are catabolized with virtually identical kinetics; and 3) this catabolic relationship in vitro reflects the loss of hyaluronate and proteoglycans from native, undissociated aggregates as isolated from the tissue. We conclude that hyaluronate catabolism is an integral part of the overall mechanism of proteoglycan resorption in cartilage and that further understanding of this process may be key to the elucidation of the regulatory pathways for proteoglycan resorption in health and disease. PMID- 3346214 TI - Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. AB - The asparagine-linked sugar chains of human erythropoietin produced by recombinant Chinese hamster ovary cells and naturally occurring human urinary erythropoietin were liberated by hydrazinolysis and fractionated by paper electrophoresis, lectin affinity chromatography, and Bio-Gel P-4 column chromatography. Both erythropoietins had three asparagine-linked sugar chains in one molecule, all of which were acidic complex type. Structural analysis of them revealed that the sugar chains from both erythropoietins are quite similar except for sialyl linkage. All sugar chains of erythropoietin produced by recombinant Chinese hamster ovary cells contain only the NeuAc alpha 2----3Gal linkage, while those of human urinary erythropoietin contain the NeuAc alpha 2----6Gal linkage together with the NeuAc alpha 2----3Gal linkage. The major sugar chains were of fucosylated tetraantennary complex type with and without N-acetyllactosamine repeating units in their outer chain moieties in common, and small amounts of 2,4 and 2,6-branched triantennary and biantennary sugar chains were detected. This paper proved, for the first time, that recombinant technique can produce glycoprotein hormone whose carbohydrate structures are common to the major sugar chains of the native one. PMID- 3346213 TI - Dynamic pattern of estradiol binding to uterine receptors of the rat. Inhibition and stimulation by unsaturated fatty acids. AB - The binding of estradiol to uterine cytosoluble receptors from 24-day-old rats was reduced or potentiated by unsaturated fatty acids (NEFAs), depending on the concentrations of estradiol and unsaturated NEFAs. At estradiol concentrations of up to 1.5 x 10(-8) M, unsaturated NEFAs inhibited estradiol binding to the 8 S cytosol receptor. This inhibition was dose-dependent (10-70%, p less than 0.001) and a function of NEFA unsaturation. Scatchard analysis indicated that unsaturated NEFAs caused a large decrease in receptor affinity for estradiol. Polyunsaturated NEFAs had no apparent effect on estradiol binding at estradiol concentrations of 2-4 x 10(-8) M. At high estradiol concentrations (above 4 x 10( 8) M), estradiol binding was increased 130-250% (p less than 0.01) by polyunsaturated NEFAs. This increased binding was particularly associated with proteins sedimenting at 12.5 S and the 8 S binding was, in fact, reduced. Metabolic studies showed that the reduced binding in the presence of unsaturated fatty acids was correlated with a decrease in reversibly bound estradiol at low estradiol concentrations. The increase in estradiol binding at high estradiol concentrations is the result of a reduction in reversibly bound estradiol and an increase in nonorganic solvent-extractable (water-soluble) estradiol. The amounts of these water-soluble estradiol derivatives depended on both estradiol and unsaturated NEFA concentrations. 70% of the water-soluble estradiol derivatives were trichloroacetic acid-precipitable, suggesting a covalent protein-steroid link. Thus, changes in the hydrophobic fatty acid environment of the uterine cytosol estrogen receptor could modify estrogen-receptor function by altering binding site conformation and/or by inducing changes in estradiol metabolism. PMID- 3346216 TI - Thermodynamics of hydrolysis of sugar phosphates. AB - Thermodynamics of the enzyme-catalyzed (alkaline phosphatase, EC 3.1.3.1) hydrolysis of glucose 6-phosphate, mannose 6-phosphate, fructose 6-phosphate, ribose 5-phosphate, and ribulose 5-phosphate have been investigated using microcalorimetry and, for the hydrolysis of fructose 6-phosphate, chemical equilibrium measurements. Results of these measurements for the processes sugar phosphate2- (aqueous) + H2O (liquid) = sugar (aqueous) + HPO2++-(4) (aqueous) at 25 degrees C follow: delta Ho = 0.91 +/- 0.35 kJ.mol-1 and delta Cop = -48 +/- 18 J.mol-1.K-1 for glucose 6-phosphate; delta Ho = 1.40 +/- 0.31 kJ.mol-1 and delta Cop = -46 +/- 11 J.mol-1.dK-1 for mannose 6-phosphate; delta Go = -13.70 +/- 0.28 kJ.mol-1, delta Ho = -7.61 +/- 0.68 kJ.mol-1, and delta Cop = -28 +/- 42 J.mol 1.K-1 for fructose 6-phosphate; delta Ho = -5.69 +/- 0.52 kJ.mol-1 and delta Cop = -63 +/- 37 J.mol-1.K-1 for ribose 5-phosphate; and delta Ho = -12.43 +/- 0.45 kJ.mol-1 and delta Cop = -84 +/- 30 J.mol-1.K-1 for the hydrolysis of ribulose 5 phosphate. The standard state is the hypothetical ideal solution of unit molality. Estimates are made for the equilibrium constants for the hydrolysis of ribose and ribulose 5-phosphates. The effects of pH, magnesium ion concentration, and ionic strength on the thermodynamics of these reactions are considered. PMID- 3346215 TI - Thermodynamics of isomerization reactions involving sugar phosphates. AB - Thermodynamics of isomerization reactions involving sugar phosphates have been studied using heat-conduction microcalorimetry. For the process glucose 6 phosphate2-(aqueous) = fructose 6-phosphate2- (aqueous), K = 0.285 +/- 0.004, delta Go = 3.11 +/- 0.04 kJ.mol-1, delta Ho = 11.7 +/- 0.2 kJ.mol-1, and delta Cop = 44 +/- 11 J.mol-1.K-1 at 298.15 K. For the process mannose 6-phosphate2- (aqueous) = fructose 6-phosphate2- (aqueous), K = 0.99 +/- 0.05, delta Go = 0.025 +/- 0.13 kJ.mol-1, delta Ho = 8.46 +/- 0.2 kJ.mol-1, and delta Cop = 38 +/- 25 J.mol-1.K-1 at 298.15 K. The standard state is the hypothetical ideal solution of unit molality. An approximate result (-14 +/- 5 kJ.mol-1) was obtained for the enthalpy of isomerization of ribulose 5-phosphate (aqueous) to ribose 5-phosphate (aqueous). The data from the literature on isomerization reactions involving sugar phosphates have been summarized, adjusted to a common reference state, and examined for trends and relationships to each other and to other thermodynamic measurements. Estimates are made for thermochemical parameters to predict the state of equilibrium of the several isomerizations considered herein. PMID- 3346217 TI - Oxidative metabolism of the carcinogen 6-fluorobenzo[c]phenanthrene. Effect of a K-region fluoro substituent on the regioselectivity of cytochromes P-450 in liver microsomes from control and induced rats. AB - Oxidative metabolism of the carcinogen 6-fluorobenzo[c]phenanthrene (6-FB[c]Ph) was compared with that of benzo[c]phenanthrene (B[c]Ph) to elucidate the enhancement of carcinogenicity of B[c]Ph by the 6-fluoro substituent. Liver microsomes from untreated (control), phenobarbital-treated, and 3 methylcholanthrene-treated rats metabolized 6-FB[c]Ph at rates of 3.5, 1.5, and 7.7 nmol of products/nmol of cytochrome P-450/min, respectively. The rates of metabolism of B[c]Ph by the same microsomes were 2.9, 1.6, and 5.5 nmol of products/nmol of cytochrome P-450/min, respectively. Whereas the K-region 5,6 dihydrodiol was the major metabolite of B[c]Ph, the major metabolite of 6-FB[c]Ph was the K-region 7,8-oxide, which underwent slow rearrangement to an oxepin. Thus, the 6-fluoro substituent blocks oxidation at the 5,6-double bond and inhibits hydration of the K-region 7,8-oxide by epoxide hydrolase. Substitution with fluorine at C-6 caused an almost 2.5-fold increase in the percentages of the putative proximate carcinogens, i.e. benzo-ring dihydrodiols with bay-region double bonds, when liver microsomes from 3-methylcholanthrene-treated rats were used. Little or no increase was observed in their formation by liver microsomes from control or phenobarbital-treated rats. Interestingly, liver microsomes from control rats formed almost 3-fold as much 3,4-dihydrodiol as isosteric 9,10 dihydrodiol. The R,R-enantiomers of the 3,4- and 9,10-dihydrodiols and the S,S enantiomer of the 7,8-dihydrodiol were predominantly formed by all three microsomal preparations. PMID- 3346218 TI - Conformational restrictions of the sheep testicular receptor discriminates pituitary lutropin and placental gonadotropins. AB - A membrane preparation from the testis of maturing Dorset-Leicester-Suffolk sheep, capable of discriminating pituitary LH (lutropin) from placental gonadotropins human choriogonadotropin (hCG) and equine choriogonadotropin is described. Maximum binding of 125I-oLH (ovine lutropin) to the testicular receptors occurred at 4 degrees C in a rapid manner, attaining equilibrium in 12 16 h. Under such optimal conditions, only unlabeled ovine LH or the structurally identical bovine LH effectively competed for receptor occupation. Other highly purified pituitary LH preparations from rat and human pituitaries were weakly (4 10%) active in displacement assays. Purified hCG or equine choriogonadotropin, which were highly potent in rat testicular LH receptor assays, could not compete with 125I-oLH for binding to the sheep LH receptor at 4 degrees C. Thus, the sheep testicular LH receptor was highly specific in recognizing pituitary LH conformation. The presence of an ovine/bovine LH alpha- or beta-subunit in recombinants with hCG subunit counterparts was required to generate an effective conformation capable of receptor recognition. Chemically deglycosylated hCG, containing 75% less carbohydrate and which showed greater binding to other LH receptors, failed to recognize sheep LH receptor, suggesting that excess carbohydrate in hCG was not a factor in hindering binding of the native placental hormone. Scatchard analysis using 125I-hCG/125I-oLH revealed that there were separate sites with similar affinities but vastly different capacities. The hCG binding sites, which could also be effectively occupied by oLH, were less than 10% of oLH binding sites. Thus, the Dorset-Leicester-Suffolk sheep testicular receptor provides an important and unique in vitro test system to distinguish pituitary LH from placental LH-like hormones. We infer that temperature-dependent conformational restrictions of the sheep testicular LH receptor are involved in recognizing differences in these highly similar and structurally homologous hormones. PMID- 3346219 TI - The reaction of bovine alpha-thrombin with tetranitromethane. Characterization of the modified protein. AB - Previous studies from several laboratories have shown that thrombin is inactivated by tetranitromethane with the formation of nitrotyrosine. The inactivation is characterized by an apparently greater loss of fibrinogen clotting activity than activity toward synthetic ester substrates, suggesting that the residues modified by tetranitromethane are involved in the interaction of thrombin with fibrinogen. This study was designed 1) to determine the effect of solvent conditions on the rate of modification and the stoichiometry of the reaction of tetranitromethane with bovine alpha-thrombin; 2) to identify the residue(s) modified; and 3) to characterize the modified enzyme with respect to its interaction with peptide nitroanilide substrates and fibrinogen. The inactivation of thrombin by tetranitromethane proceeded more rapidly in 50 mM Tris, pH 8.0, than in 50 mM sodium phosphate, 100 mM NaCl, pH 8.0. Approximately 10% fibrinogen-clotting activity remained at maximal inactivation. A study of the effect of tetranitromethane concentration on the rate of inactivation suggested that the loss of activity was the result of the modification of 1 mol of tyrosine/mol of thrombin. A similar result was obtained from the analysis of the extent of inactivation as a function of the extent of protein modification. Structural analysis of the modified protein showed substantial modification at both Tyr71 and Tyr85. Enzyme kinetic studies were performed with the modified protein and a control thrombin with N2-tosylglycylprolylarginine p-nitroanilide. H-D-phenylalanylpipecolylarginine p-nitronailide, and purified bovine fibrinogen. With all three substrates, a substantial decrease in kcat was observed, whereas there was essentially no change in Km. These results suggest that, contrary to previous suggestions, the modification of Tyr71 and Tyr85 in thrombin does not influence the binding of substrates, but rather influences active site reactivity. PMID- 3346220 TI - Cysteinesulfonate and beta-sulfopyruvate metabolism. Partitioning between decarboxylation, transamination, and reduction pathways. AB - L-Cysteinesulfonate (L-cysteate) is present in plasma, urine, and tissues in concentrations comparable to that of L-cysteinesulfinate, the primary oxidative metabolite of L-cysteine. Although cysteinesulfonate is known to be decarboxylated to taurine by cysteinesulfinate decarboxylase, the occurrence and importance of other metabolisms has not been examined. The present studies indicate that cysteinesulfonate partitions in vivo between decarboxylation and transamination; the latter reaction is catalyzed by aspartate aminotransferase and yields beta-sulfopyruvate. Whereas beta-sulfinylpyruvate, the product of cysteinesulfinate transamination, decomposes spontaneously, beta-sulfopyruvate is stable and is reduced by malate dehydrogenase to beta-sulfolactate. When L-[1 14C]cysteinesulfonate is given to mice, 60-75% is decarboxylated to taurine and about 25% is excreted in the urine as beta-sulfolactate. beta-Sulfo[1-14C] pyruvate is found to partition about equally between beta-sulfolactate and cysteinesulfonate formation; greater than 90% of the latter is decarboxylated. Parenterally administered beta-sulfo[1-14C]lactate is mostly excreted in the urine, but 12% is metabolized via beta-sulfopyruvate and cysteinesulfonate to 14CO2 and taurine. beta-Sulfopyruvate is not excreted, and only traces of sulfoacetate, perhaps formed by oxidative decarboxylation, are detected. These studies establish that cysteinesulfonate, beta-sulfopyruvate, and beta sulfolactate are reversibly interconverted in vivo. Since only cysteinesulfonate is directly metabolized to CO2, the rate of 14CO2 formation from L-[1 14C]cysteinesulfonate is a valid measure of total cysteinesulfinate decarboxylase activity in vivo; use of this assay permits inhibitor effects to be accurately determined in intact mice. Thus, whereas in vitro assays indicate that beta methyleneaspartate inhibits brain, liver, and kidney cysteinesulfinate decarboxylase by 0, greater than 60, and 90%, respectively, in vivo studies with L-[1-14C]cysteinesulfonate show net metabolic inhibition is about 40%. PMID- 3346221 TI - Biochemistry of terminal deoxynucleotidyltransferase. Affinity labeling and identification of the deoxynucleoside triphosphate binding domain of terminal deoxynucleotidyltransferase. AB - Using the technique of UV-mediated cross-linking of nucleotides to their acceptor sites (Modak, M. J., and Gillerman-Cox, E. (1982) J. Biol. Chem. 257, 15105 15109), we have labeled calf terminal deoxynucleotidyltransferase (TdT) with [32P]dTTP. The specificity of dTTP cross-linking at the substrate binding site in TdT is demonstrated by the competitive inhibition of the cross-linking reaction by other deoxynucleoside triphosphates, and ATP and its analogues, requiring concentrations consistent with their kinetic constants. Tryptic peptide mapping of the [32P]dTTP-labeled enzyme showed the presence of a single radioactive peptide fraction that contained the site of dTTP cross-linking. The amino acid composition and sequence analysis of the radioactive peptide fraction revealed it to contain two tryptic peptides, spanning residues 221-231 and 234-249. Since these two peptides were covalently linked to dTTP, the region encompassed by them constitutes a substrate binding domain in TdT. Further proteolytic digestion of the tryptic peptide-dTTP complex, using V8 protease, yielded a smaller peptide, and its analysis narrowed the substrate binding domain to 14 amino acids corresponding to residues 224-237 in the primary amino acid sequence of TdT. Furthermore, 2 cysteine residues, Cys-227 and Cys-234, within this domain were found to be involved in the cross-linking of dTTP, suggesting their participation in the process of substrate binding in TdT. PMID- 3346223 TI - Free and protein-conjugated polyamines in mouse epidermal cells. Effect of high calcium and retinoic acid. AB - We have investigated polyamine metabolism in primary cultures of mouse epidermal cells. These cells, which grow at low Ca2+ levels as a monolayer with characteristics of basal cells, terminally differentiate when the extracellular Ca2+ level is raised above 1 mM. The cellular levels of free polyamines were measured, and, after incubation of cell cultures with [3H]putrescine, the distribution of label in both acid-soluble and acid-insoluble cellular components was examined. Free polyamine levels were reduced in cells induced to differentiate. Treatment with retinoic acid, which prevents differentiation and causes increased proliferation, resulted in an increase in free putrescine. Upon adjustment of the calcium concentration to a level that induces differentiation, the enzyme transglutaminase was activated, and a concomitant increase in the level of both protein-bound mono- and bis-gamma-glutamyl derivatives of putrescine and spermidine was observed. Isolation of a material of apparent molecular weight about 6000 which contains only mono-gamma-glutamylpolyamines and the finding of both mono- and bis-gamma-glutamylpolyamines in the protein fraction containing cornified cell envelopes provided the basis for speculation on polyamines in envelope formation. Our data suggest that polyamines play a role during epidermal cell differentiation through transglutaminase-mediated post translational modification. PMID- 3346222 TI - Endocytosis of superoxide dismutase is required in order for the enzyme to protect hepatocytes from the cytotoxicity of hydrogen peroxide. AB - Inhibitors of endocytosis have been used to show that internalization of superoxide dismutase is required for the enzyme to protect hepatocytes from the cytotoxicity of hydrogen peroxide. As shown previously (Starke, P. E., and Farber, J. L. (1985) J. Biol. Chem. 260, 10099-10104), superoxide dismutase prevented the killing of cultured hepatocytes by H2O2 generated in the medium by glucose oxidase. Five inhibitors of endocytosis, methylamine, monensin, benzyl alcohol, cytochalasin B, and oligomycin, each abolished the protective effect of superoxide dismutase. Cell-associated superoxide dismutase activity was increased 4-fold in hepatocytes after exposure to superoxide dismutase for 1 h. Each of the inhibitors abolished this increase in the cell-associated superoxide dismutase activity. The uptake of horseradish peroxidase, a measure of fluid phase endocytosis, differed from that of superoxide dismutase in its lower rate, reduced sensitivity to methylamine, and its insensitivity to cytochalasin B. The results of the present study demonstrate that endocytosis of superoxide dismutase is required to protect hepatocytes from the cytotoxicity of hydrogen peroxide. This conclusion may account for some of the conflicting results in the literature with respect to the protective action of superoxide dismutase. PMID- 3346224 TI - A kinetic analysis of electron transport across chromaffin vesicle membranes. AB - Some types of secretory vesicles, such as the chromaffin vesicles of the adrenal medulla, have cytochrome b561 which is believed to mediate the transfer of electrons across the vesicle membrane. To characterize the kinetics of this process, we have examined the rate of electron transfer from ascorbate trapped within chromaffin vesicle ghosts to external ferricyanide. The rate of ferricyanide reduction saturates at high ferricyanide concentrations. The reciprocal of the rate is linearly related to the reciprocal of the ferricyanide concentration. The internal ascorbate concentration affects the y intercept of this double-reciprocal plot but not the slope. These observations and theoretical considerations indicate that the slope is associated with a rate constant k1 for the oxidation of cytochrome b561 by ferricyanide. The intercept is associated with a rate constant k0 for the reduction of cytochrome b561 by internal ascorbate. From k0 and standard reduction potentials, the rate constant k-0 for the reduction of internal semidehydroascorbate by cytochrome b561 can be calculated. Under conditions prevailing in vivo, this rate of semidehydroascorbate reduction appears to be much faster than the expected rate of semidehydroascorbate disproportionation. This supports the hypothesis that cytochrome b561 functions in vivo to reduce intravesicular semidehydroascorbate thereby maintaining intravesicular ascorbic acid. PMID- 3346225 TI - Prothrombinase complex assembly. Kinetic mechanism of enzyme assembly on phospholipid vesicles. AB - The kinetics of the assembly of the prothrombinase complex was studied using factor Xa modified with the active site-directed fluorophore dansylglutamylglycylarginyl chloromethyl ester (DEGR.Xa) as a reporter for the process. Stopped-flow kinetic studies of prothrombinase assembly were undertaken at saturating concentrations of calcium ion, using vesicles composed of phosphatidylcholine and phosphatidylserine (PCPS), factor Va, and DEGR.Xa. The rate of complex formation, studied under pseudo first-order conditions, depended on the premixing protocol used to initiate complex assembly and was most rapid when prothrombinase assembly was initiated by reacting Va with the preformed DEGR.Xa.PCPS complex. Under these conditions, reaction rate was linearly dependent on the concentration of PCPS with no evidence for saturation and was independent of the concentration of VA. Essentially identical reaction rates were observed when the association of Va with PCPS was independently assessed by stopped-flow light scattering. The data indicate that prothrombinase assembly initiated by mixing Va with the DEGR.Xa.PCPS complex is rate limited by the initial reaction between Va and available combining sites on the vesicle surface (k = 5.7 x 10(7) M-1.s-1) followed by extremely rapid reactions (k greater than 1 x 10(9) M-1.s-1) between PCPS-bound DEGR.Xa and PCPS-bound Va. The formation of a separate Va.PCPS complex is therefore required for prothrombinase assembly to proceed. Reaction rates obtained when prothrombinase assembly was initiated by reacting DEGR.Xa with the preformed Va.PCPS complex or by reacting PCPS with a mixture of DEGR.Xa and Va were lower. Under these initiation conditions, reaction rates were inhibited by increasing concentrations of factor Va. These data indicate that the formation of the DEGR.Xa.PCPS binary complex is also a prerequisite for prothrombinase assembly. The second-order rate constant for the reaction between factor Xa and PCPS (k = 2.9 x 10(7) M-1.s-1) and the first-order rates of dissociation of the Va.PCPS complex (koff = 0.17 s-1) and the Xa.PCPS complex (koff = 3.3 s-1) were independently determined by stopped-flow light scattering. Collectively, the data are consistent with the interpretation that prothrombinase assembly proceeds via the initial formation of separate Xa.PCPS and Va. PCPS binary complexes at near diffusion-limited rates on the same vesicle. The lipid-bound constituents then react rapidly via rearrangements on the vesicle surface to form prothrombinase. PMID- 3346226 TI - Organization of the terminal two enzymes of the heme biosynthetic pathway. Orientation of protoporphyrinogen oxidase and evidence for a membrane complex. AB - Protoporhyrinogen oxidase (EC 1.3.3.4), the penultimate enzyme of the heme biosynthetic pathway, catalyzes the removal of six hydrogens from protoporphyrinogen IX to form protoporphyrin IX. The enzyme in eukaryotes is associated with the inner mitochondrial membrane. In the present study we have examined requirements for solubilization of this enzyme and find that it behaves as an intrinsic membrane protein that is solubilized only with detergents such as sodium cholate. The in situ orientation of the enzyme with respect to the inner mitochondrial membrane places the active site on the cytosolic face of this membrane rather than the matrix side where the active site of ferrochelatase, the terminal pathway enzyme, is located. Examination of the kinetics of the two terminal enzymes in mitochondrial membranes demonstrates that substrate channeling occurs between these terminal two-pathway enzymes. However, examination of solubilized and membrane-reconstituted enzymes shows no evidence for a stable complex. Based upon these and previous data a model for the terminal three-pathway enzymes is presented. PMID- 3346227 TI - The post-translational trimethylation of diphthamide studied in vitro. AB - The amino acid diphthamide is a complex post-translational derivative of histidine that exists in eukaryotic and Archaebacterial elongation factor 2 (EF 2). Diphtheria toxin and Pseudomonas exotoxin A catalyze the transfer of an ADP ribose residue from NAD to diphthamide, causing the inactivation of EF-2. We have used cytosolic extracts of mutant CHO-K1 cells to study the biosynthesis of diphthamide in vitro. We have identified chromatographically a precursor form of diphthamide that exists in one complementation group of mutant cells and have documented the addition of 3 methyl residues from S-adenosylmethionine to this precursor. We have identified the presence of methyltransferase capable of carrying out this reaction in vitro in cells of 15 diverse eukaryotic species. PMID- 3346228 TI - Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression, and comparison with the human liver and muscle isozymes. AB - We have cloned the cDNA encoding a new isozyme of glycogen phosphorylase (1,4-D glucan:orthosphosphate D-glucosyltransferase, EC 2.4.1.1) from a cDNA library prepared from a human brain astrocytoma cell line. Blot-hybridization analysis reveals that this message is preferentially expressed in human brain, but is also found at a low level in human fetal liver and adult liver and muscle tissues. Although previous studies have suggested that the major isozyme of phosphorylase found in all fetal tissues is the brain type, our data show that the predominant mRNA in fetal liver (24-week gestation) is the adult liver form. The protein sequence deduced from the nucleotide sequence of the brain phosphorylase cDNA is 862 amino acids long compared with 846 and 841 amino acids for the liver and muscle isozymes, respectively; the greater length of brain phosphorylase is entirely due to an extension at the far C-terminal portion of the protein. The muscle and brain isozymes share greater identity with regard to nucleotide and deduced amino acid sequences, codon usage, and nucleotide composition than either do with the liver sequence, suggesting a closer evolutionary relationship between them. Spot blot hybridization of the brain phosphorylase cDNA to laser-sorted human chromosome fractions, and Southern blot analysis of hamster/human hybrid cell line DNA reveals that the exact homolog of the newly cloned cDNA maps to chromosome 20, but that a slightly less homologous gene is found on chromosome 10 as well. The liver and muscle genes have previously been localized to chromosomes 14 and 11, respectively. This suggests that the phosphorylase genes evolved by duplication and translocation of a common ancestral gene, leading to divergence of elements controlling gene expression and of structural features of the phosphorylase proteins that confer tissue-specific functional properties. PMID- 3346229 TI - Molecular cloning and characterization of cDNA for eukaryotic transcription factor S-II. AB - Complementary DNA (cDNA) clones encoding a transcription factor S-II were isolated and characterized. The primary structure of S-II was determined by nucleotide sequence analysis of these clones. The predicted primary structure was consistent with the model that we proposed previously from the results of biochemical analyses of S-II. Using these clones as probes, we analyzed the mRNA for S-II. RNA blot analysis demonstrated the presence of four species of mRNA that hybridized with S-II cDNA in Ehrlich ascites tumor cells. This is the first evidence of polymorphism of mRNA encoding a transcription factor of RNA polymerase II. The results of analysis of the genomic structure suggested that the polymorphism of mRNA may be due to alternative splicing, or differences in initiation or termination of transcription. PMID- 3346230 TI - Chemical cross-linking of arginyl-glycyl-aspartic acid peptides to an adhesion receptor on platelets. AB - A chemical cross-linking approach has been used to characterize the interaction of platelets with small peptides of 7 and 14 residues containing the arginyl glycyl-aspartic acid (RGD) sequence recognized by a variety of cellular adhesion receptors. The radioiodinated peptides were bound to platelets, and chemical cross-linking was attained by subsequent addition of bifunctional reagents. Three different cross-linking reagents coupled the RGD-containing peptides to platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa), and both subunits of this platelet membrane glycoprotein became radiolabeled with the RGD peptides. Platelet stimulation with agonists including thrombin, phorbol myristrate acetate, and ADP increased the extent of cross-linking by predominantly enhancing the coupling of the RGD peptides to the GPIIIa subunit. Cross-linking of the labeled RGD peptides to GPIIb and GPIIIa on stimulated and nonstimulated platelets exhibited structural specificity and was inhibited by excess nonlabeled RGD peptides. The interactions were inhibited by nonlabeled RGD peptides and a peptide with an amino acid sequence corresponding to the carboxyl terminus of the gamma chain of fibrinogen but less effectively by an arginyl-glycyl-glutamic acid peptide. Cross linking of the RGD peptides to GPIIb-IIIa was divalent ion-dependent and, on stimulated platelets, was inhibited by the adhesive proteins fibrinogen and fibronectin, but not by albumin. These results indicate that the RGD-binding sites on platelets reside in close proximity to both subunits of GPIIb-IIIa and that platelet stimulation alters the topography of these sites such that the peptides become more efficiently cross-linked to GPIIIa. PMID- 3346231 TI - Crystallization and preliminary analysis of crystals of apolipophorin III isolated from Locusta migratoria. AB - Crystals of apolipophorin III, isolated from the locust Locusta migratoria, have been reproducibly grown from ammonium sulfate solutions and are well suited for an x-ray crystallographic analysis. Locust apolipophorin III is a glycosylated protein with a molecular weight of 19,100 and interacts with lipophorin, the major lipoprotein complex in insects. The crystals belong to the space group P6122 or P6522 with unit cell dimensions of a = b = 67.5 A, c = 155.6 A and diffract to a nominal resolution of 2.5 A. They are physically robust and are stable in the x-ray beam for over a week. A complete native x-ray data set has been collected and processed to 3.0-A resolution. PMID- 3346232 TI - Characterization of the somatogenic receptor in rat liver. Hydrodynamic properties and affinity cross-linking. AB - Rat liver somatogenic receptors have been characterized by gel permeation chromatography, sucrose density gradients in H2O and D2O, and affinity cross linking using 125I-bovine growth hormone (bGH) as a specific somatogenic receptor ligand. Cross-linking of 125I-bovine growth hormone to a Triton X-100-treated low density fraction isolated from livers of late pregnant rats followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis under reducing conditions showed three major binders with Mr 95,000, 86,000, and 43,000 and a minor binder of Mr 55,000, after correction for bound ligand assuming a 1:1 binding ratio of ligand-receptor. The Mr 86,000, 55,000, and 43,000 species were recovered in the detergent-soluble supernatant after high-speed centrifugation, whereas the Mr 95,000 species remained Triton X-100 insoluble. Detergent-soluble 125I-bGH receptor complexes were further analyzed by sedimentation into sucrose density gradients. The sedimentation coefficient was S20,w = 5.2 S and the partial specific volume v = 0.72 ml/g. Gel permeation chromatography on a Sepharose S-400 column indicated a Stokes radius of 61 A for the 125I-bGH-receptor-Triton X-100 complex. Based on these figures, the molecular weight of the complex was calculated as 131,100. The molecular weight of the ligand-free receptor-Triton X 100 complex was calculated as Mr 109,100. Affinity cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the 61 A peak from Sephacryl S-400 chromatography (cf. above) showed two binding entities, one major and one minor with Mr values 86,000 and 43,000, respectively, in the absence of reductant. When electrophoresis was run in the presence of reductant the Mr 43,000 species was the major binding entity. Furthermore, two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis (first dimension, nonreducing and second dimension, reducing) showed that a disulfide-linked binder at Mr 43,000 is contained within the Mr 86,000 species. As with pregnant rats, female and male rats both showed 125I-bovine growth hormone binders of Mr 95,000, 84,000, 55,000, 43,000, and additionally an Mr 35,000 binder. PMID- 3346233 TI - Evaluation of the role of rat liver Golgi endo-alpha-D-mannosidase in processing N-linked oligosaccharides. AB - Golgi membranes from rat liver have been shown to contain an endo-alpha-D mannosidase which can convert Glc1Man9GlcNAc to Man8GlcNAc with the release of Glc alpha 1----3Man (Lubas, W. A., and Spiro, R. G. (1987) J. Biol. Chem. 262, 3775-3781). We now report that this enzyme has the capacity to cleave the alpha 1 ---2 linkage between the glucose-substituted mannose residue and the remainder of the polymannose branch in a wide range of oligosaccharides (Glc3Man9GlcNAc to Glc1Man4GlcNAc) as well as glycopeptides and oligosaccharide-lipids. Whereas the tri- and diglucosylated species (Glc3Man9GlcNAc and Glc2Man9GlcNAc), which yielded Glc3Man and Glc2Man, respectively, were processed more slowly than Glc1Man9GlcNAc, the monoglucosylated components with truncated mannose chains (Glc1Man8GlcNAc to Glc1Man4GlcNAc) were trimmed at an increased rate which was inversely related to the number of mannose residues present. The endomannosidase was not inhibited by a number of agents which are known to interfere with N linked oligosaccharide processing by exoglycosidases, including 1 deoxynojirimycin, castanospermine, bromoconduritol, 1-deoxymannojirimycin, swainsonine, and EDTA. However, Tris and other buffers containing primary hydroxyl groups substantially decreased its activity. After Triton solubilization, the endomannosidase was observed to be bound to immobilized wheat germ agglutinin, indicating the presence of a type of carbohydrate unit consistent with Golgi localization of the enzyme. The Man8GlcNAc isomer produced by endomannosidase action was found to be processed by Golgi enzymes through a different sequence of intermediates than the rough endoplasmic reticulum generated Man8GlcNAc variant, in which the terminal mannose of the middle branch is absent. Whereas the latter oligosaccharide is converted to Man5GlcNAc via Man7GlcNAc and Man6GlcNAc at an even rate, the processing of the endomannosidase derived Man8GlcNAc stalls at the Man6GlcNAc stage due to the apparent resistance to Golgi mannosidase I of the alpha 1,2-linked mannose of the middle branch. The results of our study suggest that the Golgi endomannosidase takes part in a processing route for N-linked oligosaccharides which have retained glucose beyond the rough endoplasmic reticulum; the distinctive nature of this pathway may influence the ultimate structure of the resulting carbohydrate units. PMID- 3346234 TI - Preliminary x-ray investigation of an orthorhombic crystal of hevein. AB - Hevein, a small protein from the latex of Hevea brasiliensis, has been crystallized by the vapor diffusion method using 2-methyl-2,4-pentanediol and CaCl2 as the precipitant agents. The crystals are orthorhombic space group P21212 with a = 21.88, b = 31.90, and c = 51.24 A and one molecule in the asymmetric unit. The crystals are quite stable to x-rays and suitable for a high resolution three-dimensional structure determination. PMID- 3346235 TI - Haloperidol binding to monoclonal antibodies. Predictions of three-dimensional combining site structure via computer modeling. AB - The amino acid sequences of five monoclonal antibodies (designated mAbs A-E) which bind to the dopaminergic D-2 antagonist, haloperidol, with a variety of affinities (Kd = 4-810 nM), have been used to build theoretical, three dimensional, computer models of the variable region combining sites. Physiocochemical interactions which have been previously determined from in vitro binding data have been used to orient the drug molecule within the combining site model. The results indicate that hydrophobic, aromatic, and ionic amino acids are involved in specific interactions with the antagonist molecule. For example, fluorescence quenching data suggests that a tryptophan residue is intimately involved in the binding of haloperidol by mAb A. Examination of the modeled structure reveals five tryptophans within the variable fragment, only one of which (H-50) is within the classical beta-barrel binding pocket and is readily accessible to the antigen. Haloperidol's relatively electron poor fluorophenyl ring system stacks with the electron-rich tryptophan ring system at a distance of 3.3 A and in so doing, places haloperidol's positively charged piperidinyl nitrogen atom within hydrogen bond distance of the negatively charged Glu-95 and Asp-100A residues of the H3 loop (Glu-H-95 and Asp-H-100A). This type of analysis for each antibody provides an interesting profile of changes in amino acid composition and hypervariable loop length which markedly effect binding affinity and specificity for a series of proteins which have similar combining site. PMID- 3346236 TI - Purification and characterization of a ferredoxin from acetate-grown Methanosarcina thermophila. AB - A ferredoxin, which functions as an electron acceptor for the CO dehydrogenase complex from Methanosarcina thermophila, was purified from acetate-grown cells. It was isolated as a trimer having a native molecular weight of approximately 16,400 and monomer molecular weight of 4,888 calculated from the amino acid composition. The ferredoxin contained 2.80 +/- 0.56 Fe atoms and 1.98 +/- 0.12 acid-labile sulfide. UV-visible absorption maxima were 395 and 295 nm with monomeric extinction coefficients of epsilon 395 = 12,800 M-1 cm-1 and epsilon 295 = 14,460 M-1 cm-1. The A395/A295 ratio ranged from 0.80 to 0.88. There were 5 cysteines per monomer but no methionine, histidine, arginine, or aromatic amino acids. The N-terminal amino acid sequence showed a 4-cysteine cluster with potential to coordinate a Fe:S center. The protein was stable for 30 min at 70 degrees C, but denatured during incubation at 85 degrees C. PMID- 3346237 TI - Glucuronic acid- and branched sugar-containing glycolipid antigens of Mycobacterium avium. AB - The pentasaccharide hapten of the dominant glycopeptidolipid antigen of serovariant 19 of the Mycobacterium avium complex is noteworthy because of the uniqueness of its distal glycobiose, the presumed antigen determinant, which contains a 3,4-di-O-methyl glucuronic acid and a novel branched sugar. The detailed structure of the entire pentasaccharide has been established by high field 1H and 13C NMR, fast atom bombardment/mass spectrometry, and various specific degradations as 3,4-di-O-Me-beta-D-GlcAp-(1----3)-2,4-di-O-Me-3-C-Me-3,6 dideox yhexosyl-(1----3)-alpha-L-Rhap-(1----3)-alpha-L-Rhap-( 1----2)-6-dT al; the extreme acid lability of the novel penultimate sugar presented special structural challenges. Thus, the task of defining the variable epitopes of M. avium serovariants in order to charter the epidemiology of opportunistic mycobacterial diseases continues to reveal an unexpected order of sugar diversity and complexity. PMID- 3346239 TI - Inhibitors of sterol synthesis. Metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol 15-one after intravenous administration to bile duct-cannulated rats. AB - The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one has been studied after intravenous administration to bile duct-cannulated rats. Very rapid and substantial conversion of the 15-ketosterol to polar biliary metabolites was observed in both male and female rats. For example, upon intravenous injection of [4-14C]5 alpha-cholest-8(14)-en-3 beta-ol-15-one to male bile duct-cannulated rats, approximately 86% of the administered 14C was recovered in bile in the first 38 h. Of the total amount of 14C recovered in bile in 38 h, approximately 50% was excreted in bile in the first 70 min and approximately 90% was excreted within 8 h after the injection of the 15-ketosterol. A substantial fraction of the polar biliary metabolites was shown to undergo enterohepatic circulation. Of the radioactivity derived from the labeled 15-ketosterol which was not recovered in bile or other excreta at 48 h after the intravenous administration of the 15 ketosterol, most (approximately 79%) was recovered in the form of cholesterol and cholesteryl esters of blood and the various tissues. The very substantial and rapid biliary excretion of polar metabolites of the 15-ketosterol (or of cholesterol derived from the 15-ketosterol), coupled with inhibition of the intestinal absorption of cholesterol by the 15-ketosterol, may contribute to the overall hypocholesterolemic action of the 15-ketosterol which has been observed in rodents and in nonhuman primates by providing a metabolic pathway(s) wherein a substantial fraction of the absorbed 15-ketosterol is rapidly removed from the body by biliary excretion in the form of polar metabolites. PMID- 3346238 TI - Inhibitors of sterol synthesis. Metabolism of [2,4-3H]5 alpha-cholest-8(14-)-en-3 beta-ol-15-one after intravenous administration to a nonhuman primate. AB - The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of cholesterol synthesis with marked hypocholesterolemic activity, has been studied after the intravenous administration of a mixture of [2,4-3H]5 alpha cholest-8(14)-en-3 beta-ol-15-one and [4-14C] cholesterol to a baboon. The levels of 3H in plasma which was associated with the free 15-ketosterol decreased very rapidly (T1/2 approximately 9 min) after injection of the labeled sterol. By 4 h, the level of the [3H]15-ketosterol in plasma was negligible. The rapid decrease in the levels of the free 15-ketosterol was associated with rapid formation of fatty acid esters of the 15-ketosterol. The maximum level of 3H-labeled 15 ketosteryl esters was observed at 20 min after the injection of the 15 ketosterol. Thereafter, the levels of the 15-ketosteryl esters decreased rapidly with an apparent T1/2 of approximately 3.5-4.0 h. The results also indicated rapid formation of 3H-labeled cholesterol and cholesteryl esters. Substantial formation of [3H]cholesterol was observed at 20 min after the injection of the 15 ketosterol and reached a maximum level in plasma at 2 h. The maximum levels of [3H]cholesteryl esters in plasma were observed much later. These and other findings indicated that the observed slow clearance of total 3H from plasma is a consequence of metabolism of the 15-ketosterol to cholesterol and cholesteryl esters, normal constituents of plasma whose turnover in the whole animal is known to be relatively slow. PMID- 3346241 TI - Comparative affinities of the epimeric reaction-intermediate analogs 2- and 4 carboxy-D-arabinitol 1,5-bisphosphate for spinach ribulose 1,5-bisphosphate carboxylase. AB - 2-Carboxy-3-keto-D-arabinitol 1,5-bisphosphate is a tightly bound intermediate of the carboxylase reaction of ribulosebisphosphate carboxylase/oxygenase. Two stereoisomers of an analog of this intermediate, 2-carboxy-D-arabinitol 1,5 bisphosphate (2CABP) and 4-carboxy-D-arabinitol 1,5-bisphosphate (4CABP), are exceptionally potent, virtually irreversible inhibitors of the spinach carboxylase, presumably due to their structural similarity to the gem-diol (hydrated carbonyl at C-3) form of the intermediate. Incubation of the enzyme with either leads to time-dependent loss of activity. Inhibition of the enzyme is biphasic, with initial dissociation constants of 0.47 and 0.19 microM and maximal rates for tight complex formation of 2.2 and 1.8 min-1 for 2CABP and 4CABP, respectively. These values give second-order rate constants for tight complex formation of 7.8 x 10(4) and 1.6 x 10(5) M-1 s-1. To determine the overall affinity of the spinach enzyme for 2CABP and 4CABP, the release rates were determined by dual isotope exchange (3H-inhibitor complex with free 14C inhibitor). Exchange half-times of 1.82 and 530 days were observed for 4CABP and 2CABP, respectively. Overall dissociation constants of 28 pM (2.8 x 10(-11) M) and 190 fM (1.9 x 10(-13) M) were calculated from these dissociation rates together with the rates of association determined by inactivation kinetics. The difference in affinity of 2CABP and 4CABP corresponds to 2.9 kcal/mol, presumably reflecting the difference in interaction of the enzyme with the two hydroxyls of the intermediate's gem-diol. The kinetic behavior of these two inhibitors, in particular the rather slow maximal rates of association, are consistent with the expected behavior of analogs of a labile intermediate of an enzymic reaction that is far more stable than a transition state. PMID- 3346240 TI - Degradation of the precursor of mitochondrial aspartate aminotransferase in chicken embryo fibroblasts. AB - The precursor of mitochondrial aspartate aminotransferase accumulates in the cytosol of cultured chicken embryo fibroblasts if its import into mitochondria is inhibited by an uncoupling agent. However, its accumulation is limited by degradation with a half-life of only approximately 5 min (Jaussi, R., Sonderegger, P., Fluckiger, J., and Christen, P. (1982) J. Biol. Chem. 257, 13334 13340). The aim of the present study was the characterization of the proteolytic system(s) responsible for this very rapid intracellular degradation. On depleting chicken embryo fibroblasts of ATP, the rate of degradation of the precursor was lowered by approximately 70%. Chicken embryo fibroblasts depleted of divalent metal ions showed a degradative activity of 10% of the initial value. Reconstitution of these cells with Mg2+ and Ca2+ increased the degradative activity from 10 to 107 and 24%, respectively. Thiol reagents almost completely prevented the degradation, whereas specific peptide inhibitors of cysteine proteases or inhibitors of intralysosomal proteolysis decreased the rate of degradation by only approximately 30%. Inhibitors of serine proteases had little effect. No rapid degradation of the precursor was observed in crude extracts of chicken embryo fibroblasts. The data indicate that the bulk of the precursor accumulated under conditions of import block is degraded by one or several cytosolic proteases dependent on ATP, Mg2+, and thiol groups of unknown localization, conceivably by proteolytic enzymes identical with or similar to one of the high molecular weight cytosolic proteases (Waxman, L., Fagan, J.M., Tanaka, K., and Goldberg, A. L. (1985) J. Biol. Chem. 260, 11994-12000). The rest of the precursor appears to be degraded by lysosomes. PMID- 3346242 TI - Small-angle x-ray scattering investigation of the solution structure of troponin C. AB - X-ray crystallographic studies of troponin C (Herzberg, O., and James, M.N.G. (1985) Nature 313, 653-659; Sundaralingam, M., Bergstrom, R., Strasburg, G., Rao, S.T., and Roychowdhury, P. (1985a) Science 227, 945-948) have revealed a novel protein structure consisting of two globular domains, each containing two Ca2+ binding sites, connected via a nine-turn alpha-helix, three turns of which are fully exposed to solvent. Since the crystals were grown at pH approximately 5, it is of interest to determine whether this structure is applicable to the protein in solution under physiological conditions. We have used small-angle x-ray scattering to examine the solution structure of troponin C at pH 6.8 and the effect of Ca2+ on the structure. The scattering data are consistent with an elongated structure in solution with a radius of gyration of approximately 23.0 A, which is quite comparable to that computed for the crystal structure. The experimental scattering profile and the scattering profile computed from the crystal structure coordinates do, however, exhibit differences at the 40-A level. A weak Ca2+-facilitated dimerization of troponin C was observed. The data rule out large Ca2+-induced structural changes, indicating rather that the molecule with Ca2+ bound is only slightly more compact than the Ca2+-free molecule. PMID- 3346243 TI - Implications of protein folding. Additivity schemes for volumes and compressibilities. AB - Partial specific volume and compressibility properties of the extended state of proteins are estimated from additivity schemes using revised amino acid and peptide data. These calculated properties are compared with the experimental data of the native state in order to assess the contribution from folding. Results of this treatment show that, in the case of partial specific volumes, there is close agreement between the two data sets for a number of proteins. The implication is that subtle compensatory contributions in volume occur during the folding process. In the case of compressibilities, however, a substantial difference is observed which is believed to arise because of the hydrophobic interior created in the native protein as a result of the folding process. Using suitable measures of protein hydrophobicities and estimates of the fraction of buried apolar residues, a "micellar model of protein compressibility" is proposed and tested for several proteins. Results obtained from this model show good agreement with the experimental data for the native state of a number of proteins. PMID- 3346244 TI - Reciprocal regulation of sex-dependent expression of testosterone 15 alpha hydroxylase (P-450(15 alpha)) in liver and kidney of male mice by androgen. Evidence for a single gene. AB - Testosterone 15 alpha-hydroxylase activities and its mRNA levels are higher in kidneys than in livers from male 129/J mice. Castration of 129/J male mice resulted in repression of P-450(15 alpha) in kidney, but increased it in liver. Two types of cDNA (p15 alpha-29 (Type I) and -15 (Type II)) encoding P-450(15 alpha) were previously cloned from 129/J female livers (Burkhart, B.A., Harada, N., and Negishi, M. (1985) J. Biol. Chem. 260, 15357-15361). With the use of p15 alpha-29 as a probe, Type I and II P-450(15 alpha) cDNAs were isolated from libraries of 129/J kidney poly(A)+ RNA. The nucleotide sequences of the cDNAs showed that Type I and II cDNAs from liver and kidney were identical and shared 98.3% similarity. The deduced amino acid sequence from a full-length Type I cDNA indicated that Type I P-450(15 alpha) consists of 494 amino acids with a molecular weight of 56,594. Nine amino acid substitutions were found in the Type II clone in 432 amino acids overlapping Type I. Type I cDNA clones accounted for approximately 90% P-450(15 alpha) clones isolated from a male kidney library, whereas approximately 90% of cDNA clones in a female kidney library were Type II. Liver cDNA libraries from males and females contained similar ratios of Type I and II. Effects of castration on Type I and II mRNAs were determined by Southern hybridization of a 32P-labeled ClaI-ClaI fragment from p15 alpha-29 to cDNAs synthesized from kidney and liver poly(A)+ RNAs prepared from sham-operated, castrated 129/J mice. The double-stranded cDNAs were digested with ClaI and PstI prior to gel electrophoresis to create the diagnostic restriction fragments specific for Type I or II. Castration resulted in decreased levels of Type I mRNA in male kidney. In male liver, only Type I mRNA rose significantly in response to castration. Testosterone administration returned the Type I mRNA to normal levels in castrated mice. It therefore appears that the high levels of P-450(15 alpha) in male kidney were due to androgen-dependent induction of Type I mRNA. Both Types I and II were repressed in male liver, which results in decreased levels of P-450(15 alpha). Androgen was responsible for the repression and expression of Type I in liver and kidney, but not Type II. PMID- 3346245 TI - Studies on the gamma-glutamyl Cu-binding peptide from Schizosaccharomyces pombe. AB - The gamma-glutamyl peptide induced in Schizosaccharomyces pombe in response to metal stress has been purified following exposure of the organism to cadmium and copper salts. Induction of the peptide enables S. pombe to proliferate in media containing high concentrations of cadmium and copper. Two Cd-gamma-Glu peptide complexes are produced which differ in the content of acid-labile sulfur. One Cu gamma-Glu peptide complex is induced, and it lacks acid-labile sulfur in the metal-binding cluster. The peptides are composed of repeating dipeptide units of gamma-Glu-Cys with a carboxyl-terminal glycine with heterogeneity observed in the repeat unit n. The number of repeats averages 3.2 and 3.8 for the Cd-peptides I and II and 3.6 for the Cu-peptide, in the case of the Cu-complex peptides with n values from 2 to 4 were separated by reverse phase high pressure liquid chromatography. The Cu-gamma-Glu peptide complex is oligomeric, but the exact number of peptide units per complex is not known. The copper binding stoichiometry averages 2.3 g atoms of Cu/mol of peptide, whereas Cd-peptides I and II average 1.8 and 2.7 mol eq of Cd(II)/peptide unit. The pH of half dissociation of Cu ions from the gamma-Glu peptide is near 1.3, whereas pH values of 4 and 5.4 are sufficient for half-displacement of Cd ions from the sulfide containing and -lacking peptides II and I, respectively. In the Cu-peptide complex copper is bound as Cu(I) as the complex exhibits luminescence characteristic of Cu(I)-S chelation. The luminescence emission peaks at 619 nm with a corrected excitation peak centered at 290 nm. The luminescence of the Cu complex indicates the clustering of Cu(I) ions within a solvent-inaccessible complex. The complex is air-labile as the luminescence emission is gradually lost upon air exposure. PMID- 3346246 TI - Biosynthesis of MAM-6, an epithelial sialomucin. Evidence for involvement of a rare proteolytic cleavage step in the endoplasmic reticulum. AB - MAM-6 is a major epithelial sialomucin which is abundantly present at the apical surface of ductal and alveolar cells of normal tissues and on many different carcinoma cells. MAM-6, as defined by monoclonal antibodies, consists of one or two sialylated glycoproteins with apparent molecular masses of over 400 kDa under reducing as well as nonreducing conditions. The mobility and number of glycoproteins immunoprecipitated vary depending on the cell line of origin. We have employed immunoprecipitation techniques to study the biosynthesis and glycosylation of this mucin. The biosynthesis of MAM-6 was studied in the ZR-75-1 breast cancer cell line. Two glycoproteins with apparent molecular masses of approximately 450 and 650 kDa, representing the mature form, were immunoprecipitated. By pulse-chase analysis, we show that the biosynthesis of the 450-kDa glycoprotein proceeded through intermediates of 220, 200, and 500 kDa which became perceptible after 1, 4, and 30 min, respectively. The biosynthesis of the 650-kDa glycoprotein followed a similar course through 380, 350, and 700 kDa intermediates. The processing of the 220- and 350-kDa precursors involves a rare proteolytic cleavage step which occurs in the endoplasmic reticulum. The late precursors of 500/700 kDa, observed after 30 min chase, and the mature glycoproteins were generated by extensive O-linked glycosylation. The formation of the 500/700-kDa precursors was not affected by monensin. However, the final step of maturation, sialylation of the 500/700-kDa precursors, could be inhibited by monensin. The extensive O-linked glycosylation causes the apparent high molecular weight as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Our data on the biosynthesis show that the early MAM-6 precursors contain N-linked glycans, suggesting the presence of N-linked glycans on the mature MAM-6 molecule. Although the copresence of N- and O-linked glycans has been found on many molecules, no N-linked glycans have been reported on mucus glycoproteins previously. PMID- 3346247 TI - Horse heart metmyoglobin. A 2.8-A resolution three-dimensional structure determination. AB - The structure of horse heart metmyoglobin has been determined with a molecular replacement approach and subsequently refined using rigid body and restrained parameter least squares methods to a conventional crystallographic R-factor of 0.16 for all observed reflections in the 6.0-2.8-A resolution range. The polypeptide chain of this protein is found to be organized into eight helical regions (labeled A-H) which collectively form a hydrophobic pocket in which the heme prosthetic group is bound. Our results show that the overall thermal motions of individual residues of horse heart metmyoglobin are correlated with their mean distances from the heme group. In comparisons with the structure of sperm whale metmyoglobin it has been found that horse heart metmyoglobin has unique polypeptide chain conformations in four regions. These include residues in the immediate vicinity of the amino and carboxyl termini, residues about Lys-16, and residues 117-124 which are in the interhelical region between helices G and H. Many of these conformational changes appear to occur as a consequence of a different pattern of salt-bridging interactions between charged residues on the surface of horse heart metmyoglobin. The overall average positional deviation observed between corresponding alpha-carbons in the polypeptide chains of horse heart and sperm whale metmyoglobin is 0.50 A. This value for atoms of the porphyrin core of the central heme group is 0.39 A. A total of 12 well defined water molecules and 1 sulfate ion are included in the current structural model of horse heart metmyoglobin. One of these water molecules is found to be coordinated to the heme iron atom and hydrogen bonded to the side chain of His-64. The sulfate ion is hydrogen bonded to amide groups at the amino-terminal end of the E helix and, as well, forms similar interactions with the amino-terminal end of the D-helix of an adjacent protein molecule in the crystalline lattice. PMID- 3346248 TI - Structure, expression, and evolution of the 5-enolpyruvylshikimate-3-phosphate synthase genes of petunia and tomato. AB - 5-Enolpyruvylshikimate-3-phosphate (EPSP) synthase is an enzyme of the shikimate pathway which is located in the chloroplasts in higher plants. This enzyme is the target of the nonselective herbicide glyphosate. We have isolated and sequenced cDNA clones encoding EPSP synthase from petunia and tomato. The deduced amino acid sequences of the two enzyme precursors show 93% identity in the mature protein regions and 58% identity in the transit peptides. The sequences of the plant enzymes show significantly greater similarity to bacterial EPSP synthases than to fungal EPSP synthases. A genomic clone containing an EPSP synthase gene was isolated from a library of petunia DNA and was shown to contain seven intervening sequences. This gene is expressed approximately 25-fold higher in flower petals than in other organs of petunia. Transcription of this gene is initiated at multiple sites in petunia leaves and in a glyphosate-tolerant petunia cell line overproducing EPSP synthase mRNA. In petals, however, transcription of this gene is initiated almost entirely from only one of these sites. In contrast to petunia, the levels of EPSP synthase mRNA in different organs of tomato do not differ significantly. PMID- 3346249 TI - The effect of nonenzymatic glucosylation on the binding of the main noncollagenous NC1 domain to type IV collagen. AB - Type IV collagen has the ability to self-assemble by amino end, carboxyl end, and lateral associations to complex network-like structures which can be visualized by rotary shadowing. The main noncollagenous NC1 domain which is located at the carboxyl end of type IV collagen molecules binds to itself to form dimers and also binds along the length of type IV collagen. The latter binding initiates lateral assembly. Following in vitro nonenzymatic glucosylation of the isolated NC1 domain, binding to the helix-rich domain of type IV collagen was impaired. In turbidity experiments, the nonenzymatically glucosylated NC1 domain minimally suppressed the development of turbidity of collagen solutions when compared to control NC1 domain. In rotary shadowing experiments nonenzymatically glucosylated NC1 domain did not significantly inhibit lateral associations or networks formed by type IV collagen, whereas control NC1 domain caused a drastic decrease in laterally assembled structures. These data suggest that nonenzymatic glucosylation of the NC1 domain may interfere with normal assembly of type IV collagen in diabetes mellitus and may be related to abnormal functions of basement membranes in this pathological condition. PMID- 3346250 TI - The effect of speed of deoxygenation on the percentage of aligned hemoglobin in sickle cells. Application of differential polarization microscopy. AB - We have used differential polarization microscopy, which provides images of linear dichroism, to measure the percentage of aligned hemoglobin (Hb) in 1086 deoxygenated red blood cells from subjects with sickle cell anemia. The percentage was found to be only slightly dependent on the speed of deoxygenation, thus showing that the percentage of aligned Hb was thermodynamically controlled (as has been found previously for the percentage of polymerized Hb in vitro). A slight decrease in the percentage of aligned Hb due to increasing speed of deoxygenation is primarily due to the increase in the number of cells containing no detectable aligned Hb. This class of cells was also the most variable between the different subjects studied. We were able to identify two other groups of cells that contain different numbers of domains of aligned Hb and show that these groups contain statistically different percentages of aligned Hb. The differences between these classes of cells was shown to be primarily due to different numbers of initial nucleation sites within each cell. It appears that the presence of preformed nucleation sites within cells at ambient oxygen tensions results in the thermodynamic control of aligned Hb polymer. PMID- 3346251 TI - Relationship between the levels of calbindin synthesis and calbindin mRNA in chick intestine. Quantitation of calbindin mRNA. AB - An RNA-excess filter hybridization assay was established to measure the absolute amount of calbindin mRNA in chick tissues. The tissue with the highest level of mRNA is intestine, followed by kidney and cerebellum; the mRNA was not detected in liver and skin. Calbindin mRNA in intestine and kidney is vitamin D-dependent. The maximum concentration of calbindin and its mRNA found after dosing vitamin D deficient chicks with dihydroxyvitamin D3 (1,25-(OH)2D3) is less than 5% of that found with vitamin D dosing. Secondary 1,25-(OH)2D3 stimulation produced greatly increased amounts of both calbindin mRNA and the protein, at least reaching levels similar to those found after vitamin D dosing. In this last case, each mucosal cell contains about 2000 calbindin mRNA molecules which are translated at a rate sufficient to account for the levels of calbindin found. Calbindin mRNA is translated most rapidly in the very short time periods after its release into the cytoplasm. 1,25-(OH)2D3 has two effects on calbindin mRNA formation: first, to permit the expression of the calbindin gene and a second effect, of slower onset but more persistent, which increases either the rate of calbindin gene transcription or the stability of calbindin mRNA. PMID- 3346252 TI - De novo and maintenance DNA methylation by a mouse plasmacytoma cell DNA methyltransferase. AB - A DNA methyltransferase of Mr = 140,000 that is active on both unmethylated and hemimethylated DNA substrates has been purified from the murine plasma-cytoma cell line MPC 11. The maximal rate of methylation was obtained with maintenance methylation of hemimethylated Micrococcus luteus or M13 DNAs. At low enzyme concentrations, the highest rate of de novo methylation occurred with single stranded DNA or relatively short duplex DNA containing single-stranded regions. Strong substrate inhibition was observed with hemimethylated but not unmethylated DNA substrates. Fully methylated single-stranded M13 phage DNA inhibited neither the de novo nor the maintenance reactions, but unmethylated single-stranded M13 DNA strongly inhibited the maintenance reaction. The kinetics observed with hemimethylated and single-stranded substrates could be explained if the enzyme were to bind irreversibly to a DNA molecule and to aggregate if present in molar excess. Such aggregates would be required for activity upon hemimethylated but not single-stranded DNA. For de novo methylation of duplex DNA, single-stranded regions or large amounts of methyltransferase appear to be required. The relative substrate preference for the enzyme is hemimethylated DNA greater than fully or partially single-stranded DNA greater than fully duplex DNA. PMID- 3346253 TI - Developmental regulation of tropoelastin isoforms. AB - The production of tropoelastin isoforms was examined by cell-free translation of nuchal ligament RNA from cows of various ages ranging from 110 days of gestation to adult. Tropoelastin polypeptides synthesized in vitro were immunoprecipitated with a specific monoclonal antibody and separated by high resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From these experiments three distinct tropoelastin isoform patterns were detected at different developmental periods. 1) The fetal period was characterized by three polypeptides of about 67, 65, and 63 kDa produced in a ratio of 1:3:2. 2) In neonatal tissue, the same molecular mass forms were detected; however, the relative isoform ratio changed to 2:3:1. 3) From adult ligament RNA, only the 67- and 65-kDa forms of tropoelastin were detected, and these were produced in equal amounts. The pattern of tropoelastin isoforms produced from RNA isolated from other fetal elastic tissues was the same as for fetal ligament. Additional studies demonstrated that the relative amount of functional tropoelastin mRNA correlated with steady state levels of mRNA consistent with transcriptional regulation of tropoelastin synthesis. Although the significance of developmental switching of individual tropoelastin isoforms is unknown, it is likely that this process is required for proper assembly and, thus, function of elastic tissue. PMID- 3346254 TI - Studies on the assembly of apo B-100-containing lipoproteins in HepG2 cells. AB - The relationship between apoB-100 and the membrane of the endoplasmic reticulum (ER) has been studied by a combination of pulse-chase methodology and subcellular fractionation. HepG2 cells were pulse-labeled with [35S]methionine for 3 min and chased with cold methionine for periods between 0 and 20 min. ApoB-100 and albumin, present in the membrane as well as in the luminal content of the ER vesicles, were isolated after each chase period. The results indicated that apoB 100 was cotranslationally bound to the membrane of the ER, and from this membrane bound form, was transferred to the lumen after a delay of 10-15 min. Albumin was, as could be expected for a typical secretory protein, cotranslationally sequestered in the lumen of the ER. Apo-B-100-containing lipoproteins present in the microsomal lumen were analyzed by ultracentrifugation in a sucrose gradient. ApoB-100 occurred on rounded particles in three density regions: (i) d 1.1065 1.170 g/ml (Fraction I), (ii) d 1.011-1.045 g/ml (Fraction II), and (iii) d less than 1.011 g/ml (Fraction III). Fraction I, isolated from cells cultured in the absence of oleic acid, contained a homogenous population of particles with a mean diameter of approximately 200 A. Fraction I isolated from cells cultured in the presence of oleic acid was slightly more heterogeneous and had a mean diameter of approximately 250 A. Fractions II and III had mean diameters of 300 and 500 A, respectively. Cholesterol esters and triacylglycerol were the quantitatively dominating lipid constituents of all three fractions. Pulse-chase experiments indicated that Fraction I contained the newly assembled lipoproteins. With increasing chase time, the apoB-100 radioactivity was redistributed from Fraction I to Fractions II and III, indicating that Fraction I is converted into Fractions II and III during the intracellular transfer. Particles corresponding to Fractions II and III were by far the most abundant lipoproteins found in the medium. The results presented support the possibility of a sequential assembly of apoB-100-containing lipoproteins. PMID- 3346255 TI - 5-Fluorouracil substitution alters pre-mRNA splicing in vitro. AB - We are interested in determining whether incorporation of the drug 5-fluorouracil into pre-mRNA can alter RNA processing. The effect of 5-fluorouracil (FUra) substitution on the in vitro splicing of pre-mRNA was studied. 32P-Labeled human beta-globin pre-mRNA containing the first two exons and the first intervening sequence was synthesized in the presence of UTP, FUTP, or both. In vitro splicing reactions generated several abnormal intermediates and products from FUra substituted transcripts. The appearance of a new minor spliced product was dependent on both the pH of the splicing reaction and the extent of FUra incorporation into pre-mRNA. Abnormal splicing was observed at pH 8.4 and 7.7 but not at pH 6.7. The new minor spliced product was sequenced and found to contain an additional 20 bases derived from the 3'-end of the intervening sequence. The abnormally migrating intermediate had the same structure as the normal lariat exon intermediate. These results suggest that FUra substitution into pre-mRNA can alter splicing in vitro. PMID- 3346256 TI - Conformational aspects of the acid-induced fusion mechanism of influenza virus hemagglutinin. Circular dichroism and fluorescence studies. AB - Circular dichroism and tryptophan fluorescence spectroscopy have been used to investigate the structures of the influenza virus membrane glycoprotein hemagglutinin, acid-treated hemagglutinin, and fragments of hemagglutinin derived by proteolysis. The conformational change in hemagglutinin which occurs at the pH of membrane fusion (pH 5-6) was associated with a significant change of the environment of tyrosine residues, a change in the environment of tryptophan residues, but no changes in secondary structure. Tryptic digestion of the hemagglutinin in its low pH conformation which releases one of the subunit polypeptides (HA1) caused minimal changes in tyrosine and tryptophan environments but a small secondary structural change in HA1. The secondary structure of the remainder of the molecule (HA2) was very similar to that predicted from the known x-ray crystallographic structure of the native molecule. However, fluorescence spectroscopy indicated a tertiary change in structure in the coiled coil of alpha helices which form the fibrous central stem of the molecule. These results are consistent with a conformational change required for membrane fusion which involves a decrease of HA1/HA1, HA1/HA2 interactions and changes in tertiary structure not accompanied by changes in secondary structure. PMID- 3346257 TI - Identification, purification, and characterization of a stilbenedisulfonate binding glycoprotein from canine kidney brush border membranes. A candidate for a renal anion exchanger. AB - Canine renal brush border membrane proteins that bind stilbenedisulfonate inhibitors of anion exchange were identified by affinity chromatography. A 130 kDa integral membrane glycoprotein from brush border membrane was shown to bind specifically to 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate immobilized on Affi-Gel 102 resin. The bound protein could be eluted effectively with 1 mM 4 benzamido-4'-aminostilbene-2,2'-disulfonate (BADS). The 130-kDa protein did not bind to the affinity resin in the presence of 1 mM BADS or when the solubilized extract was covalently labeled with 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). This protein was labeled with [3H]H2DIDS, and the labeling was prevented by BADS. The 130-kDa protein did not cross-react with antibody raised against human or dog erythrocyte Band 3 protein. The 130-kDa protein was accessible to proteinase K and chymotrypsin digestion in vesicles but not to trypsin. The 130 kDa protein was sensitive to endo-beta-N-acetylglucosaminidase F treatment both in the solubilized state and in brush border membrane vesicles showing that it was a glycoprotein and that the carbohydrate was on the exterior of the vesicles. This glycoprotein was resistant to endo-beta-N-acetylglucosaminidase H treatment suggesting a complex-type carbohydrate structure. The protein bound concanavalin A, wheat germ agglutinin, and Ricinus communis lectins, and it could be purified using wheat germ agglutinin-agarose. PMID- 3346258 TI - The molecular basis for a cytosolic malic enzyme null mutation. Malic enzyme mRNA from MOD-1 null mice contains an internal in-frame duplication that extends the coding sequence by 522 nucleotides. AB - Many tissues from wild type mice express cytosolic malic enzyme activity and contain two mRNAs (2.0 and 3.1 kilobases (kb)) that encode a single 64-kDa malic enzyme subunit polypeptide. MOD-1 null mutant mice lack cytosolic malic enzyme activity but express 2.5- and 3.6-kb mRNAs that hybridize with wild type malic enzyme cDNAs and are induced in liver by a starvation/carbohydrate refeeding regimen. To investigate the basis of the MOD-1 null mutation, a lambda gt11 cDNA library was constructed using mRNA from the livers of induced MOD-1 null mice as a template. A recombinant phage with a 2-kb insert was isolated by screening with wild type malic enzyme cDNA probes. The subcloned insert exhibited an atypical (non-wild type) restriction pattern and was subjected to sequence analysis. MOD-1 null malic enzyme cDNA contains an internal tandemly duplicated sequence that corresponds to nucleotides 1027-1548 in the coding region of wild type murine malic enzyme cDNA (Bagchi, S., Wise, L. S., Brown, M. L., Bregman, D., Sul, H. S., and Rubin, C. S. (1987) J. Biol. Chem. 262, 1558-1565). An open reading frame is retained throughout the duplicated sequence. The discovery of a 522-nucleotide in-frame duplication accounts for the increased size of MOD-1 null malic enzyme mRNAs and suggests that a variant malic enzyme polypeptide that is 19 kDa larger than the wild type subunit might be found in mutant mice. Western immunoblot analysis disclosed that MOD-1 null liver cytosol contains an 82-kDa protein that is recognized by anti-malic enzyme antibodies. Under stringent conditions, an anti-sense 32P-oligonucleotide that spans the abnormal junction between the reiterated sequences hybridized with the 2.5 and 3.6-kb MOD-1 null malic enzyme mRNAs but failed to form stable complexes with wild type malic enzyme mRNAs. Thus, both MOD-1 null malic enzyme mRNAs contain the duplication deduced from cDNA sequence analyses. The MOD-1 null mutation might originate from an unequal crossover between homologous regions of two different introns in the malic enzyme gene, thereby causing the duplication of one or more exons. PMID- 3346259 TI - The results of tenodesis of the tendo achillis to the fibula for paralytic pes calcaneus. AB - Sixty-six consecutive tenodeses of the tendo achillis to the fibula were done in sixty patients who had paralytic pes calcaneus. The patients were followed for an average of 5.7 years (range, two to 10.8 years). The preoperative disturbance of gait was eliminated in all of the patients, and radiographic improvement was noted in the feet that had been operated on. Sixteen feet (23 per cent) required revision of the tenodesis because equinus deformity had developed. The development of equinus deformity was found to occur more often in patients who had the procedure at a younger age and in patients in whom the calcaneotibial angle measured more than 70 degrees at the time of the tenodesis. Residual cavovarus deformity was successfully treated by a plantar release. PMID- 3346260 TI - A modified extensile exposure for the treatment of complex or malunited acetabular fractures. AB - A modification of the extended iliofemoral incision of Letournel and Judet facilitates the operative exposure of T-type, complex transverse, and both-column acetabular fractures and malunions. The modification includes the utilization of a T-shaped skin incision with large flaps, and osteotomies of the iliac crest, greater trochanter, and anterior superior iliac spine. The iliotibial band is transected and the abductor muscle mass is rotated posteriorly, hinged on the superior gluteal neurovascular bundle. Twenty patients had open reduction and internal fixation of a complex acetabular fracture using this surgical approach. Excellent surgical exposure allowed good or excellent reduction of the acetabulum in all patients. No flap necrosis developed, and all fractures healed. One non union of a trochanteric osteotomy needed revision. This approach provides increased exposure of the posterior column and visualization of the entire surface of the joint and it allows fixation of the fracture from both sides of the iliac wing. The T-shaped skin incision allows utilization of a standard posterior approach with conversion to the extensile exposure if necessary. Options for late reconstruction are not compromised. Lagscrew fixation of the osteotomies allows aggressive rehabilitation of the joint. PMID- 3346261 TI - The uncemented porous-coated anatomic total hip prosthesis. Two-year results of a prospective consecutive series. AB - Fifty uncemented porous-coated total hip prostheses were implanted in forty-seven patients whose mean age was fifty-eight years. Clinical hip-rating scores, as described by Harris, were determined and anteroposterior and frog-leg lateral radiographs were made preoperatively, shortly postoperatively, and at three months, six months, one year, and two years postoperatively. The mean hip-rating score was 92 points (range, (range, 74 to 100 points) at one year and 92 points (range, 69 to 100 points) at two years. The thigh was slightly painful in nine patients (18 per cent) at one year and in eight (16 per cent) at two years. Fourteen hips (28 per cent) (in thirteen patients) caused a moderate or severe limp two years postoperatively; however, this complication appears to have been related more to the direct lateral approach that was used than to the prosthesis. Six (13 per cent) of the patients walked with a cane at one year and five (11 per cent) still required a cane at two years. Serial radiographic evaluations revealed that, between the first and second postoperative years, a progressive radiodense femoral line developed in twenty hips (41 per cent); a progressive acetabular line, in four hips (8 per cent); and progressive femoral sclerosis, in twelve hips (24 per cent). There was progressive loosening of beads from twelve (24 per cent) of the femoral components and from nine (18 per cent) of the acetabular components. The position of one acetabular and one femoral component changed. Two femoral shafts fractured, one intraoperatively and one fourteen months postoperatively. We concluded that the clinical results were encouraging in these patients at the end of two years. We are concerned, however, about the progressive radiodense lines, sclerosis, and loosening of beads as well as the slight, but persistent, pain in the thigh in eight patients. PMID- 3346262 TI - The effect of halo-vest length on stability of the cervical spine. A study in normal subjects. AB - In order to study how the efficiency of the halo vest is affected by different lengths of the vest, an experimental headband was devised that allowed the head of a normal person to be held securely in the halo attachment. The vest was then modified to allow it to be adjusted to three different lengths (Fig. 2): a full vest extended to the iliac crests, a short vest extended to the twelfth ribs, and a half vest extended to the level of the nipples. Twenty normal, healthy adult men participated in the study. For each vest length, radiographs were made of each subject demonstrating rotation, flexion-extension, and lateral bending of the cervical spine. There was no rotation of the cervical spine, regardless of the length of the vest. There was a variable degree of motion in flexion or extension of the upper part of the cervical spine with all vest lengths, but this was not statistically significant. There was definite increase of motion caudad to the level of the fifth cervical vertebra regardless of the length of the vest. We concluded that a lesion of the upper part of the cervical spine can be treated effectively by halo traction with a half vest. This will improve the comfort and care of the patient and avoid the necessity of removing the vest if emergency cardiovascular resuscitation is needed. In the treatment of lesions of the lower part of the cervical spine (caudad to the level of the fourth cervical vertebra), the use of a halo vest that extends caudad to the level of the twelfth ribs does provide additional stability. PMID- 3346263 TI - Use of the quadriceps active test to diagnose posterior cruciate-ligament disruption and measure posterior laxity of the knee. AB - Orthopaedic surgeons routinely use passive tests, in which the displacing force is applied externally, to evaluate the integrity of the ligaments of the knee. Using a quadriceps active test, in which the muscle contractures of the subject served as the displacing force, tibial displacement was measured with an arthrometer in ninety-two subjects: sixty-seven who had an acute or chronic rupture of the posterior or anterior cruciate ligament and twenty-five who had normal knees. With the knee joint in 90 degrees of flexion, contraction of the quadriceps resulted in anterior translation of the tibia in forty-one of forty two knees that had a documented disruption of the posterior cruciate ligament. This anterior translation did not occur in the contralateral, normal knee of the same subjects; in the knees of the twenty-five normal subjects; or in twenty-five knees that had a known unilateral anterior cruciate-ligament disruption. PMID- 3346264 TI - Effects of irradiation on cortical bone and their time-related changes. A biomechanical and histomorphological study. AB - The effects of high-dose irradiation on the biomechanical and morphological properties of cortical bone and their time-related changes were studied in male Sprague-Dawley rats. A single fraction of 3500 rads was applied to the middle part of the right thigh. Age and sex-matched control rats that did not receive radiation were used for comparison. Two weeks after irradiation, the animals had lost weight and disappearance of bone cells, shrunken osteocytes, and significantly decreased bone-turnover activities were noted. The bone marrow showed reduced hematopoietic elements and sinusoids with increased fat. No change in the torsional strength and geometric properties of bone was noted at this time. Six to ten weeks after irradiation, histopathological abnormalities of the bone persisted, and there was an accelerated resorption process. However, significant increases in the strength and cortical area of bone appeared only in the non-irradiated, contralateral femur. On the irradiated side, decreased cortical area and increased porosity of bone were found at fourteen to eighteen weeks when compared with the control rats. Other histomorphological properties, such as bone porosity, osteocyte count, and periosteal new-bone formation, appeared to recover eighteen weeks after irradiation, as they became similar to the values for the age-matched normal control rats. PMID- 3346265 TI - Measurements on radiographs of the foot in normal infants and children. AB - Radiographs were made of the feet of seventy-four normal infants and children who ranged in age from six to 127 months, and various angles were measured. Means and deviations of the measurements were calculated for eleven clinically useful angles. On the anteroposterior radiographs the talocalcaneal, talus-first metatarsal, and calcaneus-fifth metatarsal angles were recorded, and on the lateral radiograph the talocalcaneal, tibiocalcaneal, tibiotalar, talus-first metatarsal, and talohorizontal angles were documented. On lateral radiographs that were made with the foot in maximum dorsiflexion, the talocalcaneal and tibiocalcaneal angles were documented and the talocalcaneal index was recorded. The mean values and the ranges of normal values changed with age. These data provide a standard for assessment of initial and residual deformity in patients who have club foot, vertical talus, metatarsus adductus, or other deformities. PMID- 3346267 TI - Prophylactic knee braces and injury to the lower extremity. AB - Five hundred and eighty high-school football players were studied over a period of two seasons to determine the effect of so-called prophylactic knee braces on the lower extremity. Two hundred and forty-seven athletes who wore single-hinged braces and eighty-three who wore double-hinged braces were paired for the same season of play with 250 athletes who were similar in height, weight, and playing position but who did not wear braces. The fifty-three injuries of the knee that occurred were significantly more frequent (p less than 0.001) in the group that wore single-hinged braces than in the matched, non-braced group. While there were more injuries of the knee in the participants who were double-hinged braces than in the matched controls, who did not wear braces, the increase in the number of injuries was not significant. There was also a dramatic increase (p less than 0.01) in the number of injuries of the ankle and foot in the athletes who wore braces. Our results question the efficacy of the braces that were studied and call attention to the potentially adverse effect of the braces on adjacent joints in the ipsilateral limb. PMID- 3346266 TI - Shoulder arthrodesis using a pelvic-reconstruction plate. A report of eleven cases. AB - Eleven adults who had a flail shoulder due to brachial plexus palsy had arthrodesis of the shoulder using a single ten-hole pelvic-reconstruction plate. Both the glenohumeral and the acromiohumeral joints were fused with the shoulder in the position of 30 degrees of abduction, 30 degrees of flexion, and 30 degrees of internal rotation. No bone graft was used. The patients were immobilized in a spica cast for six weeks postoperatively. At an average follow-up of twenty-five months after the operation, the position of the arthrodesis had been maintained and solid fusion had occurred in each shoulder. No patient required removal of the plate. The pelvic-reconstruction plate is malleable and is more easily contoured in the operating room than a dynamic-compression plate. We recommend the use of a malleable pelvic-reconstruction plate when performing arthrodesis of the shoulder. PMID- 3346268 TI - Scapulothoracic dissociation. AB - Scapulothoracic dissociation is a rare entity that consists of disruption of the scapulothoracic articulation. The mechanism of injury is probably traction caused by a blunt force to the shoulder girdle. This lesion is characterized by massive soft-tissue swelling of the shoulder; lateral displacement of the scapula, measured radiographically; an injury to bone (an acromioclavicular separation, a displaced fracture of the clavicle, or a sternoclavicular disruption); a severe neurovascular injury; and a variety of upper and lower-extremity fractures. We treated fifteen patients who had this lesion, most of whom had several associated injuries. Three patients died: two from exsanguination and one from a cardiac arrest. In most patients, the damaged artery was repaired and the brachial plexus was explored. All of the twelve patients who had a complete brachial-plexus injury were left with a flail upper extremity. Most patients refused amputation. PMID- 3346269 TI - Radiographic changes in bone dimensions in asymptomatic cemented total hip arthroplasties. Results of nine to thirteen-year follow-up. AB - On twenty-six cemented total hip replacements that had been followed for an average of 10.4 years (range, nine to thirteen years), a retrospective radiographic study was done to assess dimensional changes in the cross section of the bone in a group of asymptomatic patients. Cortical dimensions were measured on radiographs and were normalized using a radiographic distortion factor that was derived from the width and length of the prosthesis. The data were then analyzed using a least-squares method. Analyses were performed for the men, for the women, and for the combined group. The results for all three groups showed a significant decrease in cortical thickness as well as widening of the medullary canal, but no periosteal expansion. PMID- 3346270 TI - Non-union of fractures in children who have osteogenesis imperfecta. AB - Although a fracture rarely fails to unite in a healthy child, non-union is not a rare occurrence in a child who has osteogenesis imperfecta. We identified twelve non-unions in ten patients from a population of fifty-two patients who had osteogenesis imperfecta. The average age of these patients when the diagnosis of non-union was made nine years, and the average age at the time of treatment was 12.5 years. All of the patients had had a decrease in functional ability as a result of the non-union. There were five femoral, four humeral, one radial, one ulnar, and one pubic non-union. Five of the non-unions were hypertrophic, and seven were atrophic. Eight of the nine ununited fractures that were operated on healed after excision of the non-union, intramedullary nailing, and bone grafting. Three of the non-unions (in two patients) were not operated on, and the one patient in whom surgery failed had an amputation. Non-union was frequently associated with repeated fractures at a progressively deforming site. PMID- 3346271 TI - Epidural abscess associated with spondylolysis. A case report. PMID- 3346272 TI - Painful cystic degeneration of the limbus in the hip. A case report. PMID- 3346273 TI - Unusual anomaly of the scapula defined by arthroscopy and computerized tomographic arthrography. Report of a case. PMID- 3346274 TI - Fracture as a complication of osteonecrosis of the tibial plateau. A case report. PMID- 3346275 TI - An unusual neurological complication of the Bristow procedure. A case report. PMID- 3346276 TI - Intra-articular fracture of the femur mimicking insufficiency of the posterior cruciate ligament. A case report. PMID- 3346277 TI - Salmonella spondylitis. A review and report of two immunologically normal patients. PMID- 3346279 TI - Core decompression of the femoral head for osteonecrosis. PMID- 3346278 TI - Adamantinoma of the spine. A case report. PMID- 3346280 TI - Anterior cruciate deficient knee, new concepts in ligament repair. PMID- 3346281 TI - Art--or science? PMID- 3346282 TI - Magnetic resonance imaging in congenital dislocation of the hip. AB - A study of structures which obstruct reduction of hip dislocation was performed on 15 hips by magnetic resonance imaging (MRI). Before treatment started, MRI studies were performed on 10 patients, six of whom were treated conservatively, after which further MRI studies helped to establish a concentric reduction. In the other four conservative treatment failed and they were operated on; in them the MRI studies were compared with arthrographic and surgical findings. In all but one of these 10 patients, MRI enabled us to differentiate between an everted and an inverted limbus. In five other patients with unsatisfactory development of the hip following closed reduction, MRI was compared with earlier arthrographic studies. MRI provided accurate anatomical information which would not have been obtained by arthrography. It clearly has great potential in assisting the surgeon to select the appropriate form of treatment. PMID- 3346283 TI - Bilaterality in slipped upper femoral epiphysis. AB - The frequency of slipping and osteoarthritis of the contralateral hip was recorded in 260 patients with slipped upper femoral epiphysis between 1910 and 1960. Twenty-three of these patients (9%) had primary bilateral slipping, 32 (12%) had a contralateral slip diagnosed later during adolescence and a further 104 (40%) had signs of contralateral slipping at follow-up 16 to 66 years later, giving a total of 159 cases (61%) with bilateral slips. Of the 104 slippings diagnosed at follow-up, 25% showed osteoarthritis. It is concluded that, with a slipped epiphysis, prophylactic contralateral pinning should be performed to avoid slipping and to reduce the risk of osteoarthritis. PMID- 3346284 TI - Low friction arthroplasty for old untreated congenital dislocation of the hip. AB - We report the replacement of 42 hips in 34 adults with untreated congenital dislocation. We used Charnley low friction implants, cementing the cup at the level of the true acetabulum after deepening and enlarging it by our own technique of cotyloplasty. Results were evaluated in 38 hips after a mean of 5.5 years. All the patients showed marked improvement, with no infection and, as yet, no late revision. The technical difficulties of the operation and the complications are discussed. PMID- 3346286 TI - Intracapsular pressures in undisplaced fractures of the femoral neck. AB - We studied intracapsular pressure in 50 patients with Garden Grade I and II subcapital fractures. Before operation pressures varied from zero to 320 mmHg, 16 patients having an intracapsular pressure of over 80 mmHg. The pressure was increased considerably by medial rotation and decreased by lateral rotation and especially by semi-flexion. From zero to 36 ml of blood was aspirated; the amount did not correlate with the intracapsular pressure. Of 25 patients who were also examined by scintimetry, 13 had reduced uptake at the femoral head before aspiration, and nine of these showed a marked increase in uptake after aspiration. Intracapsular tamponade of the hip may be one reason for the occasional occurrence of segmental collapse of the femoral head after subcapital fracture with minor displacement. PMID- 3346285 TI - The effect of trauma to the lower femoral epiphyseal plate. An experimental study in rabbits. AB - Forty-four rabbits were operated on when five weeks old; in one group a 2 mm drill-hole was made in the intercondylar portion of the right femur across the central portion of the growth plate up to the diaphysis, while in the other group a similar drill-hole of 3.2 mm was made. At 3, 6, 12 and 24 weeks after operation, specimens from the growth plates of both femora were analysed using radiographic, microradiographic, histological and histomorphometric techniques. It was found that destruction of 7% of the cross-sectional area of the growth plate caused permanent growth disturbance and shortening of the femur. PMID- 3346288 TI - The effect of total hip replacement on driving reactions. AB - The driving reactions of 25 patients were assessed before and after operation for hip replacement. Driving reactions were tested by monitoring the delay and force of brake application after an emergency signal, using a simulated driving control system. Fifteen normal subjects were also tested. Statistical analysis demonstrated significant differences between patients with either left or right hip replacement and between pre- and postoperative testing. Most patients improved by the eighth week, but some had deteriorated and did not recover until re-tested eight months after operation. It is concluded that for most patients eight weeks' delay for return to driving is appropriate, but for a minority of patients with right hip replacement recovery of reaction speed requires longer rehabilitation. PMID- 3346287 TI - Fixation of displaced subcapital femoral fractures. Compression screw fixation versus double divergent pins. AB - One hundred and twenty-seven consecutive patients with displaced subcapital fractures of the femoral neck (Garden Grade III or IV) all under 80 years of age and independently mobile, were randomly allocated to fixation with either double divergent pins or a single sliding screw-plate device. The incidence of non-union and infection in the sliding screw-plate group was significantly higher, and we believe that when internal fixation is considered appropriate multiple pinning should be used. Mobility after treatment was disappointing in about half of the patients, and we feel that internal fixation can only be justified in patients who are physiologically well preserved and who maintain a high level of activity. PMID- 3346289 TI - Intramedullary locking nails in the management of femoral shaft fractures. AB - Intramedullary locking nails have proved to be of considerable advantage when treating complex, comminuted or segmental femoral shaft fractures. We have reviewed 117 patients with 120 femoral shaft fractures treated with the Strasbourg device. These included 20 compound fractures, 13 pathological fractures and two non-unions. Rehabilitation and union rates have been very satisfactory and there have been no serious infections in the series. Comminution of the proximal femur has occurred in six patients and there have been three femoral neck fractures, but all of these have healed without further complications. PMID- 3346291 TI - The St Georg sledge for unicompartmental replacement of the knee. A prospective study of 115 cases. AB - Since 1974, we have made a prospective study in Bristol of the results of unicompartmental knee replacement using the St Georg sledge prosthesis. A total of 115 knees in 100 patients have been followed up for 2 to 12 years (mean, 4 years 9 months). Results have assessed both by the Bristol knee score and by survivorship studies on the total series of 138 knees. Results were excellent or good in 86% and fair or poor in 14%. The survivorship study (based on a definition of failure which included significant pain or a dissatisfied patient or the need for revision) showed a cumulative success rate of 76.4% at six years, with no further failures after that time. Seven knees have been revised, in most cases for deterioration of the contralateral compartment. The operation is recommended as a satisfactory and durable form of treatment for osteoarthritis affecting a single tibiofemoral compartment. PMID- 3346290 TI - Posteriorly stabilised total-condylar knee replacement. Three to eight years' follow-up of 85 knees. AB - We have reviewed 85 knees in 71 patients after total-condylar posteriorly stabilised (Insall-Burstein) knee replacement with an average follow-up of five years. Excellent or good results were obtained in 90% with an average maximum flexion of 98 degrees. The four poor results (5%) included two with deep infection, one with patellar dislocation and one with loosening. Four other knees (5%) showed signs of probable tibial loosening, but the patients were asymptomatic, the clinical results had not deteriorated with time and lucent lines had not progressed. Varus alignment of the knee and a varus tilt of more than 2 degrees of the tibial component correlated with the incidence of lucent lines around the tibial implant. No patellar stress fractures were seen but impingement symptoms were present in 20%, although they were troublesome in less than half of them. The virtue of the prosthesis lies in its versatility for use in the severely deformed joint. PMID- 3346292 TI - A fixation device for corrective osteotomy: brief report. PMID- 3346293 TI - Soft-tissue release of the knee in children with juvenile chronic arthritis. AB - We report the results of 23 soft-tissue release procedures in 15 patients who had juvenile chronic arthritis. The operation, which includes hamstring tenotomies and posterior capsulotomy, is a safe and effective way of eliminating contracture, relieving pain and improving function. PMID- 3346294 TI - Fractures of the tibial spine in children. An evaluation of knee stability. AB - Forty-five patients with fractures of the tibial spine were reviewed 3 to 10 years after injury in order to determine the degree of residual laxity of the cruciate or collateral ligaments. After fractures which had been partially or completely displaced, some anterior cruciate laxity was evident, even if patients were asymptomatic. It was also found that an anatomical reduction did not prevent either laxity or some loss of full extension of the knee. PMID- 3346296 TI - A comparison of Wilson and Hohmann osteotomies in the treatment of hallux valgus. AB - In a retrospective study we compared the results of 31 Wilson and 31 Hohmann osteotomies of the first metatarsal in the treatment of hallux valgus. There were no differences between the two operations in terms of patient satisfaction, pain relief, appearance, footwear and walking ability. First metatarsal shortening was the same after both operations, and the degree of shortening was unrelated to either the clinical or the pedobarographic findings. Although the long-term radiographic changes after the Hohmann osteotomy were more worrying, the pedobarographic patterns tended to be worse after the Wilson osteotomy. There were no poor results and the numbers of feet with the same final grade were identical in each group. However, there was abnormal loading of the lateral metatarsal heads after both osteotomies when compared with the normal foot, and hallux-contact time during the stance phase was also significantly reduced after osteotomy. PMID- 3346295 TI - Growth disturbance lines after injury of the distal tibial physis. Their significance in prognosis. AB - We reviewed 26 fractures involving the distal physis of the tibia to identify the patterns of formation and displacement of the subsequent growth disturbance lines. Twenty-one patients showed a regular "normal" pattern of line and healed with no deformity. Three patients had medical physeal arrest revealed by abnormal lines. Two other cases had a minor central physeal arrest without subsequent deformity. The pattern and character of the growth disturbance line can provide an early warning of potential deformity. PMID- 3346297 TI - A statistical study of papers in the Journal of Bone and Joint Surgery [BR] 1984. AB - The statistical quality of 103 original articles published in The Journal of Bone and Joint Surgery (British Volume) in 1984 was assessed. Some papers were found to be deficient: thus, it was not always clear how series were selected and sometimes neither the data nor the results were clearly presented. Sample sizes were frequently inadequate for the conclusions reached and statistical techniques should have been used more frequently. A majority of papers were descriptions of case series for which no comparative data were made available. It is suggested that collaborative research would best advance knowledge about the relative benefits of various managements, and that statistical advice could make a substantial contribution. PMID- 3346298 TI - Computerised tomographic assessment of the subtalar joint in calcaneal fractures. AB - Thirty-six patients with 39 fresh fractures of the calcaneus were investigated by standard radiography and by computerised tomography. It was found that the size and disposition of the fracture fragments and the degree of involvement of the posterior facet of the subtalar joint were more clearly shown by CT scanning. We recommend this technique for assessment and particularly for pre-operative planning. PMID- 3346299 TI - Familial expansile osteolysis. A new dysplasia. AB - We report 40 cases in one family of an autosomal dominant bone dysplasia, which, though similar in some aspects to Paget's disease, seems unique in some features and in its natural history. The disease shows both general and focal skeletal changes, the latter being mainly in the limbs with an onset from the second decade. Progressive osteoclastic resorption is accompanied by medullary expansion which leads to pain, severe deformity and a tendency to pathological fracture. The serum alkaline phosphatase and urinary hydroxyproline are variably elevated, while other biochemical indices are normal. Most patients had an associated deafness of early onset and loss of dentition. No previous description of this disease has been found in the literature. PMID- 3346300 TI - Scoliosis surgery and its effect on back shape. AB - Thirty-four patients with adolescent idiopathic scoliosis were assessed by radiography and the integrated shape imaging system (ISIS) both before and after spinal surgery. Twenty-seven patients underwent Harrington instrumentation, after which lateral indices of curvature were significantly improved, but changes in the transverse plane were less pronounced. Sublaminar wiring was carried out in two patients whose thoracic lordosis was corrected by the surgery. Five patients whose severe deformity had persisted after previous spinal surgery underwent costoplasty, which resulted in a significant improvement in back shape measurements. We conclude that the cosmetic deformity of the back in scoliosis is only partially corrected by operations on the spine itself, whilst costoplasty addresses the problem directly, and improves the surface shape. PMID- 3346301 TI - Spinal stenosis with meralgia paraesthetica. AB - Of 232 patients with evidence of lumbar spinal stenosis, 13 had symptoms of meralgia paraesthetica. Myelography demonstrated that in all but one of these 13 cases the L3-4 level was involved by stenosis; in 12 matched control patients with spinal stenosis, none had involvement at this level. We found that both the ligamentum flavum and the laminae at L3-4 level were thicker than in a control group. Decompressive laminectomy at the L3-4 level significantly reduced the area of hypo-aesthesia in the thigh, effecting complete cure in seven of the 11 cases. Meralgia paraesthetica is not uncommon in patients with spinal stenosis and is referable to changes at the L3-4 level. It seems that many cases of meralgia may have a spinal origin. PMID- 3346302 TI - Disruption of the lateral capsule of the shoulder. A cause of recurrent dislocation. AB - Experimental work has shown that dislocation of the shoulder may involve disruption of the capsule from its lateral humeral attachment. We report two patients with recurrent dislocation due to this injury. Lateral repair gave good results. It is suggested that this injury be considered and looked for when glenoid labral injury is minimal or absent. PMID- 3346303 TI - A biomechanical analysis of halo fixation in children. AB - The use of prolonged halo stabilisation in a child is increasingly indicated for trauma and congenital instability of the cervical spine, but complications of pin fixation in this age group are frequent. We have analysed four aspects of the mechanics of the halo pin: the forces applied by each of six surgeons was shown to vary widely, penetration of the inner table occurred relatively easily, friction at the pin-halo interface influenced forces, and the skull thickness measured by CT scan varied from 1.1 mm to 4.3 mm in children under six years of age. We recommend CT scanning of the skull before elective halo application in young children to ascertain the safest pin sites. PMID- 3346304 TI - Anterior interosseous nerve palsy following internal fixation of the proximal radius. AB - Three cases of anterior interosseous nerve palsy were diagnosed after internal fixation of fractures of the proximal radius. The suggestion that the nerve was injured at operation by bone-holding forceps was supported by operations on 12 cadaver forearms, in which the nerve was frequently trapped. Care should be taken to place such forceps in a subperiosteal plane. PMID- 3346305 TI - Supracondylar osteotomy for cubitus varus. The value of the straight arm position. AB - Supracondylar osteotomy for traumatic cubitus varus is usually considered to be difficult, and to have a significant incidence of complications. Most difficulty is in maintaining correction after operation. We report 20 osteotomies performed by a modification of French's technique and managed postoperatively with the elbow extended. When a plaster splint was used only three of seven cases had good or satisfactory results, two requiring revision. Postoperative management by straight arm traction maintained correction and achieved a good or satisfactory result in all 13 cases. This new technique is recommended. PMID- 3346306 TI - Vitamin K1 levels in proximal femoral fractures: brief report. PMID- 3346307 TI - Excision of the lunate in Kienbock's disease. Results after long-term follow-up. AB - Excision of the lunate was performed for 18 patients with Kienbock's disease; 14 were followed up for an average of almost 12 years. Carpal collapse progressed with time, but rearrangement of the remaining carpal bones preserved a satisfactory range of movement and grip strength. Degenerative changes were not severe. All the patients had relief of pain, were able to carry out their normal activities, and all but two could perform strenuous activities. PMID- 3346308 TI - Beware the sprained wrist. The incidence and diagnosis of scapholunate instability. AB - A consecutive series of 100 cases of wrist injury, other than those referred with a radial fracture, have been reviewed to determine the incidence of acute scapholunate instability; a "clenched fist" radiograph was used in addition to the routine scaphoid views. Of 19 patients with an increase in the scapholunate gap, five were eventually considered to have significant scapholunate instability, two in association with Colles' fractures. Injuries producing significant ligamentous damage and carpal instability may be as common as scaphoid fractures. They require special consideration in diagnosis and management. PMID- 3346309 TI - Prominent radial tubercle causing limited pronation: brief report. PMID- 3346310 TI - Radiographic signs of union of scaphoid fractures. An analysis of inter-observer agreement and reproducibility. AB - Inter-observer agreement and reproducibility of opinion were assessed for the radiographic diagnosis of union of scaphoid fractures on films taken 12 weeks after injury. Weighted kappa statistics were used to compare the opinions of eight senior observers reviewing 20 sets of good quality radiographs on two occasions separated by two months. There was poor agreement on whether trabeculae crossed the fracture line, whether there was sclerosis at or near the fracture and on whether the proximal part of the scaphoid was avascular. As a consequence, agreement on union also was poor; it appears that radiographs taken 12 weeks after a scaphoid fracture do not provide reliable and reproducible evidence of healing. PMID- 3346311 TI - Radiography and histology of a threaded acetabular implant. One case studied at two years. AB - Threaded acetabular components are widely used in cementless total hip replacement, despite a poor understanding of the nature of the bone-implant interface. We have examined one case in which the threaded titanium ring appeared to be well incorporated with no discernible radiolucency. Microradiography and histology surprisingly showed that the threads were entirely encapsulated in fibrous tissue. This raises doubt about the relevance of plain radiography to the analysis of the acetabular interface. PMID- 3346312 TI - Experimental microvascular growth plate transfers. Part I--Investigation of vascularity. AB - A model was developed in the dog to allow both the metaphysis and epiphysis of the distal ulnar growth plate to be microsurgically revascularised from the pedicle of the anterior interosseous vessels. With both circulations revascularised, grafts retained their structural integrity and growth continued at rates only slightly less than normal (mean 85%). If either or both circulations were not revascularised, growth rates were lower and were associated with skeletal collapse in the ischaemic bone segment. PMID- 3346313 TI - Experimental microvascular growth plate transfers. Part 2--Investigation of feasibility. AB - We investigated the feasibility in the dog of using transfers of the distal ulna into the radius either as growth plate replacements or as accessory growth plates in the diaphysis. Preliminary work determined the most satisfactory method of skeletal fixation. The experimental study showed that transfers used as growth plate replacements grew at almost normal rates, uniting with the recipient bone in a mean of 7.1 weeks. Transfers into the diaphysis initially nearly doubled the growth rate of the radius, although in the long-term results were unsatisfactory, because of fracture of the graft after a mean period of 8.2 weeks. PMID- 3346314 TI - Longitudinal bone growth after sciatic denervation in rats. AB - The right sciatic nerve of 50 one-month-old male rats was cut under general anaesthesia. Groups of animals were sacrificed at intervals of up to 12 weeks after operation and the length of the femora, tibiae and first and fifth metatarsals were measured with a caliper accurate to 0.05 mm. From the first week, both metatarsals were between 3% and 5% shorter on the denervated side, but there was no further increase of the discrepancy. The femora were less than 1% longer in the denervated limb at the second and eighth week. No difference was found between the lengths of the tibiae. The various factors which could possibly be responsible for these findings are discussed. PMID- 3346315 TI - The blood supply of the osteocutaneous free fibular graft. AB - The use of an osteocutaneous free fibular graft as a single-stage reconstructive procedure for composite tissue loss is increasingly common. Detailed anatomical study in cadavers of the blood supply to the graft demonstrates cutaneous arteries arising from the peroneal artery and then passing along the posterior surface of the lateral intermuscular septum. These vessels pierce the crural fascia and then ramify to supply the skin. Knowledge of the vascular anatomy of the skin overlying the fibula is essential to the success of the graft. PMID- 3346316 TI - The timing of tourniquet application in relation to prophylactic antibiotic administration. AB - Antibiotic levels in bone and fat were measured in patients undergoing knee replacement to determine the time that should elapse between intravenous injection and tourniquet inflation. The tissue levels increased progressively with time, and there was wide variation in absorption rate between patients and between the two cephalosporins assessed. Five minutes should probably be left between systemic injection and inflation of the tourniquet, though two minutes may be long enough for drugs which are rapidly absorbed. PMID- 3346318 TI - Surgical approaches to the dorsum of the wrist: brief report. PMID- 3346317 TI - Laminectomy versus laminoplasty for cervical myelopathy: brief report. PMID- 3346319 TI - Sciatic palsy following reduction of a dislocated prosthesis: brief report. PMID- 3346320 TI - Interprosthetic dislocation of the Charnley Hastings prosthesis: brief report. PMID- 3346321 TI - Fc receptor-mediated phagocytosis occurs in macrophages at exceedingly low cytosolic Ca2+ levels. AB - Cytosolic free Ca2+ ([Ca2+]i) homeostasis was investigated in mouse peritoneal macrophages and in the macrophage-like cell line J774. [Ca2+]i measurements were performed in both cells in suspension and cells in monolayers loaded with either quin2 or fura-2. Resting [Ca2+]i was 110-140 and 85-120 nM for cell suspensions and monolayers, respectively. There were no significant differences in [Ca2+]i between the two macrophage populations whether quin2 or fura-2 were used as Ca2+ indicators. Addition of heat-aggregated IgG, IgG-coated erythrocyte ghosts, or a rat monoclonal antibody (2.4G2) directed against mouse Fc receptor II induced a rise in [Ca2+]i. This [Ca2+]i increase was consistently observed in J774 and peritoneal macrophage suspensions and in J774 macrophage monolayers; in contrast it was observed inconsistently in peritoneal macrophages in monolayer cultures. The increase in [Ca2+]i induced by ligation of Fc receptors was inhibited totally in macrophages in suspension and by 80% in macrophages in monolayers by a short preincubation of macrophages with PMA; however, phagocytosis itself was unaffected. The effect of reducing cytosolic Ca2+ to very low concentrations on Fc receptor-mediated phagocytosis was also investigated. By incubating macrophages with high concentrations of quin2/AM in the absence of extracellular Ca2+, or by loading EGTA into the cytoplasm, the [Ca2+]i was buffered and clamped to 1-10 nM. Despite this, the phagocytosis of IgG-coated erythrocytes proceeded normally. These observations confirm the report of Young et al. (Young, J. D., S. S. Ko, and Z. A. Cohn. 1984. Proc. Natl. Acad. Sci. USA. 81:5430-5434) that ligation of Fc receptors causes Ca2+ mobilization in macrophages. However, these results confirm and extend the findings of McNeil et al. (McNeil, P. L., J. A. Swanson, S. D. Wright, S. C. Silverstein, and D. L. Taylor. 1986. J. Cell Biol. 102:1586-1592) that a rise in [Ca2+]i is not required for Fc receptor-mediated phagocytosis; and they provide direct evidence that Fc receptor-mediated phagocytosis occurs normally even at exceedingly low [Ca2+]i. PMID- 3346322 TI - Kinetics of desmosome assembly in Madin-Darby canine kidney epithelial cells: temporal and spatial regulation of desmoplakin organization and stabilization upon cell-cell contact. I. Biochemical analysis. AB - The functional interaction of cells in the formation of tissues requires the establishment and maintenance of cell-cell contact by the junctional complex. However, little is known biochemically about the mechanism(s) that regulates junctional complex assembly. To address this problem, we have initiated a study of the regulation of assembly of one component of the junctional complex, the desmosome, during induction of cell-cell contact in cultures of Madin-Darby canine kidney epithelial cells. Here we have analyzed two major protein components of the desmosomal plaque, desmoplakins I (Mr of 250,000) and II (Mr of 215,000). Analysis of protein levels of desmoplakins I and II by immunoprecipitation with an antiserum that reacts specifically with an epitope common to both proteins revealed that desmoplakins I and II are synthesized and accumulate at steady state in a ratio of 3-4:1 (in the absence or presence of cell-cell contact). The kinetics of desmoplakins I and II stabilization and assembly were analyzed after partitioning of newly synthesized proteins into a soluble and insoluble protein fraction by extraction of whole cells in a Triton X 100 high salt buffer. In the absence of cell-cell contact, both the soluble and insoluble pools of desmoplakins I and II are unstable and are degraded rapidly (t1/2 approximately 8 h). Upon induction of cell-cell contact, the capacity of the insoluble pool increases approximately three-fold as a proportion of the soluble pool of newly synthesized desmoplakins I and II is titrated into the insoluble pool. The insoluble pool becomes relatively stable (t1/2 greater than 72 h), whereas proteins remaining in the soluble pool (approximately 25-40% of the total) are degraded rapidly (t1/2 approximately 8 h). Furthermore, we show that desmoplakins I and II can be recruited from this unstable soluble pool of protein to the stable insoluble pool upon induction of cell-cell contact 4 h after synthesis; significantly, the stabilization of this population of newly synthesized desmoplakins I and II is blocked by the addition of cycloheximide at the time of cell-cell contact, indicating that the coordinate synthesis of another protein(s) is required for protein stabilization. PMID- 3346323 TI - Dynamic continuity of cytoplasmic and membrane compartments between plant cells. AB - Fluorescence photobleaching was employed to examine the intercellular movement of fluorescein and carboxyfluorescein between contiguous soybean root cells (SB-1 cell line) growing in tissue culture. Results of these experiments demonstrated movement of these fluorescent probes between cytoplasmic (symplastic) compartments. This symplastic transport was inhibited with Ca2+ in the presence of ionophore A23187, and also with the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA). Both of these agents have previously been demonstrated to inhibit gap junction-mediated cell-cell communication in animal cells. In a companion experiment, a fluorescent phospholipid analogue, N-4-nitrobenzo-2-oxa 1,3-diazole phosphatidylcholine (NBD-PC), was incorporated into soybean cell membranes to examine whether dynamic membrane continuity existed between contacting cells, a transport route not existing between animal cells. Photobleaching single soybean cells growing in a filamentous strand demonstrated that phospholipid did exchange between contiguous cells. PMID- 3346324 TI - Cytoskeleton-associated plectin: in situ localization, in vitro reconstitution, and binding to immobilized intermediate filament proteins. AB - The association and interaction of plectin (Mr 300,000) with intermediate filaments and filament subunit proteins were studied. Immunoelectron microscopy of whole mount cytoskeletons from various cultured cell lines (rat glioma C6, mouse BALB/c 3T3, and Chinese hamster ovary) and quick-frozen, deep-etched replicas of Triton X-100-extracted rat embryo fibroblast cells revealed that plectin was primarily located at junction sites and branching points of intermediate filaments. These results were corroborated by in vitro recombination studies using vimentin and plectin purified from C6 cells. Filaments assembled from mixtures of both proteins were extensively crosslinked by oligomeric plectin structures, as demonstrated by electron microscopy of negatively stained and rotary-shadowed specimens as well as by immunoelectron microscopy; the binding of plectin structures on the surface of filaments and cross-link formation occurred without apparent periodicity. Plectin's cross-linking of reconstituted filaments was also shown by ultracentrifugation experiments. As revealed by the rotary shadowing technique, filament-bound plectin structures were oligomeric and predominantly consisted of a central globular core region of 30-50 nm with extending filaments or filamentous loops. Solid-phase binding to proteolytically degraded vimentin fragments suggested that plectin interacts with the helical rod domain of vimentin, a highly conserved structural element of all intermediate filament proteins. Accordingly, plectin was found to bind to the glial fibrillar acidic protein, the three neurofilament polypeptides, and skin keratins. These results suggest that plectin is a cross-linker of vimentin filaments and possibly also of other intermediate filament types. PMID- 3346325 TI - Different forms of microtubule-associated protein 2 are encoded by separate mRNA transcripts. AB - Brain microtubule-associated protein 2 (MAP2) consists of a pair of high molecular mass (280 kD) polypeptides, MAP2a and MAP2b, and a recently identified 70-kD protein, MAP2c, which is antigenically related to these high molecular mass MAP2's. Using cDNA clones we have analyzed the expression of these three proteins at the nucleic acid level. cDNA probes selective for the high molecular mass MAP2's a and b identified only a 9-kb mRNA, whereas a probe for sequence common to all three MAP2 isoforms, a, b, and c, recognized the 9-kb transcript and additionally a 6-kb mRNA. Southern blot analysis with cDNA probes indicated that there is only one MAP2 gene from which these two distinct mRNAs are derived. The 70-kD MAP2c protein is much more abundant in neurons of developing brain than those of adult tissues. Similarly the expression of the 6-kb MAP2c-related mRNA, is much greater in neonatal than adult rat brain, indicating that the developmental expression of MAP2 is determined by transcriptional regulation from a single MAP2 gene. PMID- 3346326 TI - Probing actin polymerization by intermolecular cross-linking. AB - We have used N,N'-1,4-phenylenebismaleimide, a bifunctional sulfhydryl cross linking reagent, to probe the oligomeric state of actin during the early stages of its polymerization into filaments. We document that one of the first steps in the polymerization of globular monomeric actin (G-actin) under a wide variety of ionic conditions is the dimerization of a significant fraction of the G-actin monomer pool. As polymerization proceeds, the yield of this initial dimer ("lower" dimer with an apparent molecular mass of 86 kD by SDS-PAGE [LD]) is attenuated, while an actin filament dimer ("upper" dimer with an apparent molecular mass of 115 kD by SDS-PAGE [UD] as characterized [Elzinga, M., and J. J. Phelan. 1984. Proc. Natl. Acad. Sci. USA. 81:6599-6602]) is formed. This shift from LD to UD occurs concomitant with formation of filaments as assayed by N-(1 pyrenyl)iodoacetamide fluorescence enhancement and electron microscopy. Isolated cross-linked LD does not form filaments, while isolated cross-linked UD will assemble into filaments indistinguishable from those polymerized from unmodified G-actin under typical filament-forming conditions. The presence of cross-linked LD does not effect the kinetics of polymerization of actin monomer, whereas cross linked UD shortens the "lag phase" of the polymerization reaction in a concentration-dependent fashion. Several converging lines of evidence suggest that, although accounting for a significant oligomeric species formed during early polymerization, the LD is incompatible with the helical symmetry defining the mature actin filament; however, it could represent the interfilament dimer found in paracrystalline arrays or filament bundles. Furthermore, the LD is compatible with the unit cell structure and symmetry common to various types of crystalline actin arrays (Aebi, U., W. E. Fowler, G. Isenberg, T. D. Pollard, and P. R. Smith. 1981. J. Cell Biol. 91:340-351) and might represent the major structural state in which a mutant beta-actin (Leavitt, J., G. Bushar, T. Kakunaga, H. Hamada, T. Hirakawa, D. Goldman, and C. Merril. 1982. Cell. 28:259 268) is arrested under polymerizing conditions. PMID- 3346329 TI - The effects of heat shock on the morphology and protein synthesis of the epidermis of Xenopus laevis larvae. AB - By scanning electron microscopy, we have observed that a 20-min heat shock at 37 degrees C, although not lethal, causes extensive damage to the epidermis of 30-h and 2-d (post-fertilization) Xenopus laevis larvae. The primary effects of heat shock are the apical swelling of the epidermal cells, giving the epidermis a "cobblestone" appearance, and the selective shedding of the ciliated cells. The shed cells may be cell fragments, however, because some of them are anucleate. Shed cells also exhibit the enriched synthesis of a group of heat shock proteins of 62,000 D molecular weight, suggesting that these proteins are specific to the shed cells. Prolonged heat shock of these larvae (i.e., 30 min at 37 degrees C) results in the complete disintegration of the epidermis, followed by larval death. At later stages of development (3-d and 4-d post-fertilization), the epidermis becomes more resistant to heat-induced damage inflicted by a 20-min heat shock. This increase in resistance coincides with the development of large secretory cells and the loss of ciliated cells in the epidermis and thus parallels a change in the state of histological differentiation. PMID- 3346327 TI - A fibronectin-like molecule is present in the developing cat cerebral cortex and is correlated with subplate neurons. AB - The subplate is a transient zone of the developing cerebral cortex through which postmitotic neurons migrate and growing axons elongate en route to their adult positions within the cortical plate. To learn more about the cellular interactions that occur in this zone, we have examined whether fibronectins (FNs), a family of molecules known to promote migration and elongation in other systems, are present during the fetal and postnatal development of the cat's cerebral cortex. Three different anti-FN antisera recognized a single broad band with an apparent molecular mass of 200-250 kD in antigen-transfer analyses (reducing conditions) of plasma-depleted (perfused) whole fetal brain or synaptosome preparations, indicating that FNs are present at these ages. This band can be detected as early as 1 mo before birth at embryonic day 39. Immunohistochemical examination of the developing cerebral cortex from animals between embryonic day 46 and postnatal day 7 using any of the three antisera revealed that FN-like immunoreactivity is restricted to the subplate and the marginal zones, and is not found in the cortical plate. As these zones mature into their adult counterparts (the white matter and layer 1 of the cerebral cortex), immunostaining gradually disappears and is not detectable by postnatal day 70. Previous studies have shown that the subplate and marginal zones contain a special, transient population of neurons (Chun, J. J. M., M. J. Nakamura, and C. J. Shatz. 1987. Nature (Lond.). 325:617-620). The FN-like immunostaining in the subplate and marginal zone is closely associated with these neurons, and some of the immunostaining delineates them. Moreover, the postnatal disappearance of FN-like immunostaining from the subplate is correlated spatially and temporally with the disappearance of the subplate neurons. When subplate neurons are killed by neurotoxins, FN-like immunostaining is depleted in the lesioned area. These observations show that an FN-like molecule is present transiently in the subplate of the developing cerebral cortex and, further, is spatially and temporally correlated with the transient subplate neurons. The presence of FNs within this zone, but not in the cortical plate, suggests that the extracellular milieu of the subplate mediates a unique set of interactions required for the development of the cerebral cortex. PMID- 3346328 TI - Mitogen activation induces the enhanced synthesis of two heat-shock proteins in human lymphocytes. AB - We have used mitogenic lectin (PHA) and a monoclonal antibody (OKT3) to stimulate human peripheral blood (G0) lymphocytes, in the presence of monocytes, and have found two major preferentially synthesized proteins, 73 and 95 kD, which are induced by the mitogens. The elevated synthesis of both proteins begins approximately 4-6 h after mitogen addition (early to mid G0/G1) before entry into first S phase. Maximum synthesis of both proteins is reached by 12 h after mitogen addition when P95 synthesis represents approximately 4%, and P73 approximately 2%, of the total protein synthesis, compared with less than 0.5% for each protein in cells cultured without mitogen. Thus, the proteins appear to be major components of activated cells. We find that both P73 and P95 are induced by heat stress as well as mitogenic stimulation. The induction of the proteins is not affected by either deleting glucose from the culture media or, alternatively, by supplementing it. Using polyclonal antibodies prepared to each of the proteins isolated from mitogen activated cells and monoclonal antibodies that were raised to heat shock proteins, we are able to show that P95 is electrophoretically and immunologically identical to the HSP 90 induced by heat stress. P73 is one of the 70 kD HSPs, (termed HSC 70; Pelham, H. R. B. 1986. Cell. 46: 959-961), but is different from the most strongly heat inducible form of HSP 70 (72 kD). The distribution of both proteins in subcellular fractions of mitogen activated lymphocytes is similar to the reported localization of the respective HSP's in other cell types. The results suggest that HSP 90 and HSC 70 may have functional roles in stress response and growth processes of human lymphocytes. PMID- 3346331 TI - Adhesion of glycosaminoglycan-deficient chinese hamster ovary cell mutants to fibronectin substrata. AB - We have examined the role of cell surface glycosaminoglycans in fibronectin mediated cell adhesion by analyzing the adhesive properties of Chinese hamster ovary cell mutants deficient in glycosaminoglycans. The results of our study suggest that the absence of glycosaminoglycans does not affect the initial attachment and subsequent spreading of these cells on substrata composed of intact fibronectin or a fibronectin fragment containing the primary cell-binding domain. However, in contrast to wild-type cells, the glycosaminoglycan-deficient cells did not attach to substrate composed of a heparin-binding fibronectin fragment. Furthermore, the wild-type but not the glycosaminoglycan-deficient cells formed F-actin-containing stress fibers and focal adhesions on substrata composed of intact fibronectin. We propose, therefore, that cell surface proteoglycan(s) participate in the transmembrane linking of intracellular cytoskeletal components to extracellular matrix components which occurs in focal adhesions. PMID- 3346330 TI - Modulation of matrix adhesive responses of human neuroblastoma cells by neighboring sequences in the fibronectins. AB - Attachment and neurite extension have been measured when Platt or La-N1 human neuroblastoma cells respond to tissue culture substrata coated with a panel of complementary fragments from the individual chains of human plasma (pFN) or cellular fibronectins (cFN) purified from thermolysin digests. A 110-kD fragment (f110), which contains the Arg-Gly-Asp-Ser sequence (RGDS)-dependent cell-binding domain but no heparin-binding domains and whose sequences are shared in common by both the alpha- and beta-subunits of pFN, facilitated attachment of cells that approached the level observed with either intact pFN or the heparan sulfate binding platelet factor-4 (PF4). This attachment on f110 was resistant to RGDS containing peptide in the medium. Neurite outgrowth was also maximal on f110, and half of these neurites were also resistant to soluble RGDS peptide. Treatment of cells with glycosaminoglycan lyases failed to alter these responses on f110. Therefore, there is a second "cell-binding" domain in the sequences represented by f110 that is not RGDS- or heparan sulfate-dependent and that facilitates stable attachment and some neurite outgrowth; this domain appears to be conformation-dependent. Comparisons were also made between two larger fragments generated from the two subunits of pFN-f145 from the alpha-subunit and f155 from the beta-subunit--both of which contain the RGDS-dependent cell-binding domain and the COOH-terminal heparin-binding domain but which differ in the former's containing some IIICS sequence at its COOH terminus and the latter's having an additional type III homology unit. Heparin-binding fragments (with no RGDS activity) of f29 and f38, derived from f145 or f155 of pFN, respectively, and having the same differences in sequence, were also compared with f44 + 47 having the "extra domain" characteristic of cFN. Attachment on f145 was slightly sensitive to soluble RGDS peptide; attachment on f155 was much more sensitive. There were also differences in the percentage of cells with neurites on f145 vs. f155 but neurites on either fragment were completely sensitive to RGDS peptide. Mixing of f29, f38, or PF4 with f110 could not reconstitute the activities demonstrated in f145 or f155, demonstrating that covalently linked sequences are critical in modulating these responses. However, mixing of f44 + 47 from cFN with f110 from pFN increased the sensitivity to RGDS peptide.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346332 TI - Collagen expression, ultrastructural assembly, and mineralization in cultures of chicken embryo osteoblasts. AB - A newly defined chick calvariae osteoblast culture system that undergoes a temporal sequence of differentiation of the osteoblast phenotype with subsequent mineralization (Gerstenfeld, L. C., S. Chipman, J. Glowacki, and J. B. Lian. 1987. Dev. Biol. 122:49-60) has been examined for the regulation of collagen synthesis, ultrastructural organization of collagen fibrils, and extracellular matrix mineralization. Collagen gene expression, protein synthesis, processing, and accumulation were studied in this system over a 30-d period. Steady state mRNA levels for pro alpha 1(I) and pro alpha 2 collagen and total collagen synthesis increased 1.2- and 1.8-fold, respectively, between days 3 and 12. Thereafter, total collagen synthesis decreased 10-fold while mRNA levels decreased 2.5-fold. In contrast to the decreasing protein synthesis after day 12, total accumulated collagen in the cell layers increased sixfold from day 12 to 30. Examination of the kinetics of procollagen processing demonstrated that there was a sixfold increase in the rate of procollagen conversion to alpha chains from days 3 to 30 and the newly synthesized collagen was more efficiently incorporated into the extracellular matrix at later culture times. The macrostructural assembly of collagen and its relationship to culture mineralization were also examined. High voltage electron microscopy demonstrated that culture cell layers were three to four cells thick. Each cell layer was associated with a layer of well developed collagen fibrils orthogonally arranged with respect to adjacent layers. Fibrils had distinct 64-70-nm periodicity typical of type I collagen. Electron opaque areas found principally associated with the deepest layers of the fibrils consisted of calcium and phosphorus determined by electron probe microanalysis and were identified by electron diffraction as a very poorly crystalline hydroxyapatite mineral phase. These data demonstrate for the first time that cultured osteoblasts are capable of assembling their collagen fibrils into a bone-specific macrostructure which mineralizes in a manner similar to that characterized in vivo. Further, this matrix maturation may influence the processing kinetics of the collagen molecule. PMID- 3346333 TI - D-periodic distribution of collagen type IX along cartilage fibrils. AB - It has recently become apparent that collagen fibrils may be composed of more than one kind of macromolecule. To explore this possibility, we developed a procedure to purify fibril fragments from 17-d embryonic chicken sternal cartilage. The fibril population obtained shows, after negative staining, a uniformity in the banding pattern and diameter similar to the fibrils in situ. Pepsin digestion of this fibril preparation releases collagen types II, IX, and XI in the proportion of 8:1:1. Rotary shadowing of the fibrils reveals a d periodic distribution of 35-40-nm long projections, each capped with a globular domain, which resemble in form and dimensions the aminoterminal globular and collagenous domains, NC4 and COL3, of type IX collagen. The monoclonal antibody (4D6) specific for an epitope close to the amino terminal of the COL3 domain of type IX collagen bound to these projections, thus confirming their identity. Type IX collagen is therefore distributed in a regular d-periodic arrangement along cartilage fibrils, with the chondroitin sulfate chain of type IX collagen in intimate contact with the fibril. PMID- 3346334 TI - Collagen type I and type V are present in the same fibril in the avian corneal stroma. AB - The distribution, supramolecular form, and arrangement of collagen types I and V in the chicken embryo corneal stroma were studied using electron microscopy, collagen type-specific monoclonal antibodies, and a preembedding immunogold method. Double-label immunoelectron microscopy with colloidal gold-tagged monoclonal antibodies was used to simultaneously localize collagen type I and type V within the chick corneal stroma. The results definitively demonstrate, for the first time, that both collagens are codistributed within the same fibril. Type I collagen was localized to striated fibrils throughout the corneal stroma homogeneously. Type V collagen could be localized only after pretreatment of the tissue to partially disrupt collagen fibril structure. After such pretreatments the type V collagen was found in regions where fibrils were partially dissociated and not in regions where fibril structure was intact. When pretreated tissues were double labeled with antibodies against types I and V collagen coupled to different size gold particles, the two collagens colocalized in areas where fibril structure was partially disrupted. Antibodies against type IV collagen were used as a control and were nonreactive with fibrils. These results indicate that collagen types I and V are assembled together within single fibrils in the corneal stroma such that the interaction of these collagen types within heterotypic fibrils masks the epitopes on the type V collagen molecule. One consequence of the formation of such heterotypic fibrils may be the regulation of corneal fibril diameter, a condition essential for corneal transparency. PMID- 3346335 TI - Thermal adaptation and heat shock response of Tilapia ovary cells. AB - The growth of tissue culture TO-2 cells derived from the warm water fish Tilapia, the induction of thermotolerance, and protein synthesis profiles of these cells in response to temperature changes were examined. TO-2 cells can grow between 15 to 34 degrees, with an optimal growth temperature of 31 degrees. There is no apparent killing of the cells when the temperature is lowered to 4 degrees for up to 3 days. Survival of TO-2 cells at 43 degrees was studied after various preheat treatments: 1) acute heating at 40 degrees for 15 min followed by 31 degrees incubation, 2) chronic exposure at 37 degrees for several hr, or 3) long-term thermal adaptation at 34 degrees. The cells acquire thermotolerance from pre exposure to 37 degrees for as short as 6 hr. Preheating at 40 degrees followed by incubation at 31 degrees also induces thermotolerance against a subsequent 43 degrees heat challenge. In addition, 34 degrees thermal adapted cells are resistant to 43 degrees heating. One- and two-dimensional gel electrophoresis of proteins after heat treatments show that three major heat shock proteins with molecular weights around 87, 70, and 27 kD are preferentially synthesized. The synthesis of two additional proteins with an isoelectric point of 6.9 and molecular weights of 60 and 44 kD are significantly enhanced in 34 degrees thermal-adapted and 37 degrees chronic heated cells, but not in cells subjected to an acute heat shock at either 40 degrees or 43 degrees. On the other hand, the 27 kD heat shock proteins are mainly present in the 43 degrees, 40 degrees, and 37 degrees heat-shocked cells, but not in the 34 degrees thermal-adapted cells. PMID- 3346336 TI - Serum and growth factors regulate expression of a 43 kDa protein in smooth muscle cell cultures. AB - Smooth muscle cells respond to injury and the presence of serum factors by modulating from a quiescent contractile cell to a motile synthetic phenotype. To evaluate the biochemical response to serum exposure, we examined the proteins synthesized and secreted in response to serum. The most prominent effect of serum was the rapid production of a protein with an apparent molecular weight of 43 kDa. Removal of serum from the culture environment led to a cessation of 43 kDa protein production. The effect of exogenous heparin on 43 kDa protein production was also evaluated. Neither the 43 kDa protein nor a previously described 38 kDa protein was induced by heparin. Further, heparin treatment did not counteract the effects of serum. These studies demonstrate that an early response of vascular smooth muscle cells to serum is the production of this previously undescribed protein and that other modifications of the culture conditions did not affect its synthesis. PMID- 3346337 TI - Effects of phorbol ester on mitogen and orthovanadate stimulated responses of cultured human fibroblasts. AB - Mitogenic stimulation of quiescent human fibroblasts (HSWP) with serum or a mixture of growth factors (consisting of vasopressin, bradykinin, EGF, and insulin) stimulates the release of inositol phosphates, mobilization of intracellular Ca, activation of Na/H exchange and subsequent incorporation of [3H]-thymidine. We have determined previously that pretreatment with the tumor promoting phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate (TPA) inhibits mitogen-stimulated Na influx in HSWP cells. We report herein that TPA pretreatment also substantially inhibits the mitogen-stimulated release of inositol phosphates in HSWP cells. Half maximal inhibition of mitogen-stimulated inositol phosphate release occurs at 1-2 nM TPA. Treatment of cells with TPA alone has no effect on inositol phosphate release. The effect of TPA pretreatment on inositol phosphate release induced by individual growth factors has also been determined. Orthovanadate, reported by Cassel et al. (1984) to increase Na/H exchange in A431 cells, has been demonstrated to stimulate both Na influx and inositol phosphate release in HSWP cells. TPA pretreatment also inhibits both orthovanadate-stimulated inositol phosphate release and Na influx. In addition, orthovanadate was determined to increase intracellular Ca activity by mobilizing intracellular calcium stores, as determined with the fluorescent intracellular calcium probe fura-2. TPA pretreatment blocks orthovanadate stimulated mobilization of intracellular Ca stores. It appears clear that in HSWP cells pretreatment of cells with phorbol ester is capable of artificially desensitizing the early cellular responses to mitogenic stimuli (growth factors, orthovanadate) by blocking the signal transduction mechanism involved at a point prior to the release of inositol phosphates. We hypothesize that in HSWP cells the normal desensitization of both inositol phosphate release and Na/H exchange is mediated via activation of protein kinase C subsequent to the stimulus-mediated activation of phospholipase C and release of protein kinase C activator diacylglycerol. However it is interesting to note that TPA-mediated inhibition of these early responses in HSWP cells does not inhibit their ability to be stimulated to incorporate [3H]-thymidine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346338 TI - Transferrin and iron in cultured chick embryonic neurons: a comparison between human and chick transferrins. AB - Transferrin was not required for the short-term survival of cultured chick retinal neurons. Both human and chick transferrin failed to enhance the in vitro survival of 8- or 11-day embryonic chick retinal neurons when cultured in a defined medium. Furthermore, maintenance of neurons in the presence of chick transferrin antibody did not alter in vitro survival. Retinal neurons, however, could bind and internalize human or chick transferrin when assayed for by fluorescence immunohistochemical techniques. Binding and internalization of chick transferrin appeared to be greater than human transferrin. Iron uptake was measured in cultures maintained in the absence of transferrin. After incubation with 59FeCl3, iron uptake was 3.5 +/- 1.1 fmoles/cell. The presence of chick transferrin antibody did not significantly alter the amount of iron uptake occurring in this assay. In a comparison of human and chick transferrin mediated iron uptake, chick transferrin was 50% more effective than human transferrin in transporting iron. This study demonstrates that cultured embryonic retinal neurons are not dependent on transferrin for survival or iron uptake, although they actively bind and internalize transferrin. Results also demonstrate that whereas cultured chick retinal neurons can bind and utilize human transferrin, they do so with less efficiency than chick transferrin. PMID- 3346339 TI - Combinative ligand-receptor interactions: epinephrine depresses RAW264 macrophage antibody-dependent phagocytosis in the absence and presence of met-enkephalin. AB - Macrophages have been shown to possess cell surface receptors for opiates and catecholamines. The abilities of these ligands to affect RAW264 macrophage antibody-dependent effector activity directed against sheep red blood cells were tested. Phagocytosis was measured by the uptake of 51Cr labeled erythrocytes and optical microscopy. Cytolysis was measured by 51Cr-release assays. Met-enkephalin increased specific antibody-dependent phagocytosis in a dose-dependent fashion; the optimal dose was found to be 10(-8) M. Epinephrine diminished phagocytosis in a dose-dependent manner exhibiting a maximal inhibition at 10(-4)-10(-5) M. This inhibition can be blocked by propranolol. The combined effects of simultaneous treatment with met-enkephalin and epinephrine were measured. At the several doses tested, the combined effects of these two ligands on the amount of phagocytosis were equivalent to or more inhibitory than epinephrine alone. Thioglycolate elicited murine peritoneal macrophages demonstrated similar responses to epinephrine, met-enkephalin, and their combination. Therefore, in vitro models more closely approximating in vivo neuroregulation of macrophage function demonstrate phagocytic inhibition. PMID- 3346340 TI - Synthetic pentapeptide from the B1 chain of laminin promotes B16F10 melanoma cell migration. AB - Laminin is a basement membrane-specific glycoprotein that promotes cell adhesion, proliferation, differentiation, and tumor cell migration. Synthetic peptides from the amino acid sequence deduced from a cDNA clone of the B1 chain of laminin were tested for their ability to promote the migration of B16F10 melanoma cells. A peptide, CDPGYIGSR, that is able to mediate epithelial cell attachment to laminin was found to promote migration, and the constituent pentapeptide YIGSR was also active but to a lesser degree. This nine-amino acid peptide blocked migration of melanoma cells to laminin but had no effect on migration to fibronectin. These data suggest that the cell-binding site and migration site on laminin share a common sequence that is unique to laminin. PMID- 3346341 TI - A phorbol ester-nonproliferative variant of Swiss 3T3 cells is deficient in Na+K+Cl- cotransport activity. AB - The identity of the genetic defect(s) in Swiss 3T3 TNR-2 and TNR-9 that confers nonresponsiveness to the proliferative effect of 12-0-tetradecanoylphorbol-13 acetate (TPA) is not known. In BALB/c 3T3 cells, loss (via mutation) of a specific membrane ion transport system, the furosemide-sensitive Na+K+Cl- cotransporter, is associated with decreased responsiveness to TPA. In this study, the transport properties of parental Swiss 3T3 cells and the TPA-nonresponsive lines TNR-2 and TNR-9 were determined in the presence and absence of TPA. When the rate of 86Rb+ efflux (as a tracer for K+) was measured from each of the three cell lines, a furosemide- and TPA-inhibitable component of efflux was clearly evident in parental and TNR-9 cells but was virtually absent in TNR-2 cells. 86Rb+ influx measurements indicated the presence in parental 3T3 cells and the TNR-9 line of a substantial furosemide-sensitive flux that could be inhibited by TPA. In contrast, much less furosemide-sensitive influx was present in 3T3-TNR-2 cells and it was relatively unaffected by TPA. In both parental 3T3 and 3T3-TNR-2 cells, most of the furosemide-sensitive 86Rb+ influx is dependent on extracellular Na+ and Cl-. The apparent affinities of the transporter for these two ions, as well as for K+, were similar in both cell lines. In parental cells, the inhibition of furosemide-sensitive 86Rb+ influx was quite sensitive to TPA (K1/2 approximately equal to 1 nM) and occurred very rapidly after phorbol ester exposure. As expected because of its volume-regulatory role, inhibition of Na+K+Cl- cotransport by TPA in parental cells caused a substantial reduction in cell volume (25%). In contrast, because of the reduced level of cotransport activity in TNR-2 cells, TPA had only a slight effect on cell volume. These results suggest that the genetic defect in 3T3-TNR-2 cells (but not TNR-9 cells) responsible for nonresponsiveness to phorbol esters may be the reduction of Na+K+Cl- cotransport activity. Thus this membrane transport system may be an important component of the signal transduction pathway used by phorbol esters in 3T3 cells. PMID- 3346342 TI - High-performance liquid chromatography of amino acids, peptides and proteins. LXXXIV. Application of derivative spectroscopy to the study of column residency effects in the reversed-phase and size-exclusion liquid chromatographic separation of proteins. AB - The influence of column residency times on the reversed-phase gradient elution behaviour of human and bovine growth hormones has been investigated using on-line photodiode array spectroscopic detection. Stationary phase induced effects on protein conformation were monitored by changes in the maxima to minima ratio of the second derivative spectrum of the eluted protein. Significant changes in the second derivative ratio of the unmodified and the fully reduced and alkylated protein were observed following long incubation times, i.e. t(dwell) greater than 15 min, at the stationary phase surface in the presence of 0.1% trifluoroacetic acid before elution with a 0-75% aqueous acetonitrile gradient. The application of multi-wavelength detection in the study of equilibrium unfolding of growth hormones in urea by size-exclusion chromatography was also investigated. On-line photodiode array instrumentation and derivative spectra rationing was employed to monitor tertiary and quaternary structural changes associated with protein denaturation during a chromatographic separation. These studies clearly demonstrate the powerful detection capabilities of such instrumental approaches for the on-line evaluation of both stationary phase surface and/or mobile phase mediated changes in protein conformation. PMID- 3346343 TI - High-performance size-exclusion chromatographic determination of the potency of biosynthetic human growth hormone products. AB - A new high-performance size-exclusion chromatography method has been developed for the determination of potency of human growth hormone products. This method has been extensively validated and shown to correlate well with the hypophysectomized rat bioassay which has been used traditionally. The method is much more precise than the traditional bioassay and thus provides more reliable means of producing consistent biosynthetic human growth hormone batches. PMID- 3346344 TI - Analysis by high-performance gel permeation chromatography of hyaluronic acid in animal skins and rabbit synovial fluid. AB - The simultaneous analysis of the molecular weight and concentration of hyaluronic acid in biological samples using high-performance liquid chromatography with two gel permeation columns is described. The elution volumes of various molecular weights of hyaluronic acids were linearily related to the logarithms of their molecular weights up to 600,000. The concentration of hyaluronic acid could be determined in the range from 20 to 100 micrograms/ml, i.e., from 4 to 20 micrograms per 200 microliter injected. The method was applied to the analysis of several animal skin extracts and rabbit synovial fluid. Skin extracts from mouse, rat, guinea-pig and rabbit could be chromatographed without prior isolation and purification. Hyaluronic acids in skin were separated clearly from chondroitin sulphates and their concentrations were determined. The molecular weights were estimated simultaneously to be more than 10(6). Rabbit synovial fluids from intact joints and saline- and carrageenin-treated joints could be chromatographed directly. The chromatograms showed that the concentration of hyaluronic acid in carrageenin-treated synovial fluid is lower than that in saline-treated fluid and the molecular weight distribution is broader. This technique enabled the rapid analysis of hyaluronic acid present at low levels in biological samples. PMID- 3346345 TI - Calibration of thin-layer chromatography with flame ionization detection for the analysis of natural lipid samples. AB - Thin-layer chromatography coupled with flame ionization detection has been used to develop a method to quantitate fish lipids. Quantitation of fractionated lipid classes is usually accomplished through calibration with standards. Our work shows that various standards within a class, such as triglycerides or free fatty acids give substantially different responses to the detector. A method has been developed in which a composite sample of salmon lipid is prepared with an internal standard. This technique eliminates the variable detector response observed for compounds within a class and provides more accurate quantitation of oils from which the calibration samples were prepared. The lipid classes quantitated were triglycerides, free fatty acids, phosphatidylethanolamine and phosphatidylcholine. PMID- 3346346 TI - Hydrolysed macroporous glycidyl methacrylate-ethylene dimethacrylate copolymer sorbent for size-exclusion high-performance liquid chromatography of synthetic polymers and biopolymers. PMID- 3346347 TI - Instability of phenylthiohydantoin amino acids. PMID- 3346348 TI - Complete separation of nine equine oestrogens by high-performance liquid chromatography. PMID- 3346349 TI - Liquid chromatographic determination of serum levels of d,l-4-amino-N-(alpha methylbenzyl)-benzamide, a new benzamide anticonvulsant. AB - A method for the high-performance liquid chromatographic (HPLC) determination of serum concentrations of d,l-4-amino-N-(alpha-methylbenzyl)-benzamide and its N acetylated metabolite is described. The compounds are isolated from a 50-microL sample of serum using solid phase extraction. The compounds and internal standard are eluted from the extraction column with acetonitrile. Quantitation is performed via UV detection at 275 nm following isocratic reversed-phase (C18) separation using a ternary solvent system. The assay procedure is useful for the determination of concentrations of parent compound from 0.63 to 87.9 micrograms/mL from 50 microL of serum. PMID- 3346350 TI - Determination of estradiol 2- and 4-hydroxylase activities in mouse liver microsomes by liquid chromatography/electrochemistry. AB - A sensitive, selective, and nonradiometric assay for estradiol 2- and 4 hydroxylase activities using high-performance liquid chromatography with an electrochemical detector (LCEC) is developed. The assay relies on a liquid-solid extraction of the catechol estrogens onto alumina, followed by their elution with dilute acid. Chromatographic separation is accomplished on a C18 reversed-phase column with an isocratic system consisting of 0.05M sodium acetate in methanol/water/acetic acid 34:56:10 (V/V). Using this assay, the estrogen 2- and 4-hydroxylase activities contained in the microsomal fraction of liver from adult female mice is studied. The assay is optimized with regard to pH, substrate or enzyme concentrations, and time. The apparent km and Vmax of the 4- and 2 hydroxylase are 22.5 microM and 35.9 pmol/mg protein/min and 64.7 microM and 206.2 pmol/mg protein/min, respectively. PMID- 3346351 TI - Euthyroid hyperthyroxinemia due to a generalized 5'-deiodinase defect. AB - We studied an 11-yr-old girl with asymptomatic hyperthyroxinemia, who remained euthyroid and healthy for 5 yr of follow-up. Besides having elevated serum T4 concentrations, her serum free T4 concentrations were consistently elevated, as measured by three different methods, including equilibrium dialysis and ultrafiltration. Serum total and free T3 concentrations were in the low normal range, and serum 3,5-diiodothyronine (3,5-T2) levels were low, suggesting reduced 5'-deiodination of both T4 and T3. Serum total and free rT3 and total and free 3', 5'-T2 concentrations were all markedly elevated, whereas serum total and free 3,3'-T2 were low, suggesting unaltered 5-deiodination of T4 to rT3 and of rT3 to 3',5'-T2 in combination with reduced 5'-deiodination of rT3 and 3',5'-T2. The girl had a small diffuse goiter, her serum TSH response to TRH was exaggerated, and thyroid radioiodine uptake was elevated, suggesting slightly increased TSH secretion and, consequently, increased thyroid secretion. Both T3 and T4 administration resulted in suppressed basal as well as TRH-stimulated serum TSH concentrations, and radioiodine uptake was suppressed during T3 administration. Our data suggest reduced activity of several (all?) peripheral 5'-deiodination pathways, including possibly also thyrotroph T4 5'-deiodination. Thus, this girl seems to have a previously unrecognized syndrome of generalized 5'-deiodinase deficiency. PMID- 3346352 TI - Hypercortisolism in patients with functional hypothalamic-amenorrhea. AB - Hypercortisolism was found in patients with functional hypothalamic amenorrhea (HA) in preliminary short term studies conducted during the morning hours (0800 1100 h). This observation prompted us to characterize the circadian and pulsatile patterns of serum cortisol and LH levels at 15-min intervals for 24 h in 10 women with functional HA and in 7 normal women during the early follicular phase of their cycles. The mean integrated 24-h serum cortisol levels (area under the curve) were significantly (P less than 0.01) higher in the HA patients than in normal women. The mean cortisol levels in the HA patients were elevated (P less than 0.005) compared to those in the normal women during the daytime hours (0800 1600 h), but not during the evening (1600-2400 h) and sleeping hours (2400-0800 h). This selective hypercortisolism during the waking period of the day was almost entirely related to increased duration and amplitude of secretory episodes (peak area) rather than a change in pulse frequency. The serum cortisol increments in response to a noon meal that occurred in normal women were markedly impaired (P less than 0.01) in the HA patients. Compared with that in the normal women, mean LH pulse frequency was reduced by 30% in the HA patients. The 24-h mean LH levels and mean LH pulse amplitude were not significantly different from those in the normal women. However, among the HA patients there were marked individual differences in LH pulse frequency and amplitude, with prolonged interpulse quiescent periods, indicative of dysfunction of the hypothalamic GnRH pulse generator. We conclude that neuroendocrine activation of the ACTH-adrenal axis and inhibition of the GnRH pulse generator in women are associated with HA. Further, spontaneous resumption of normal cyclicity occurred in the majority (8 of 10) of the HA patients with no medical treatment, suggesting that this syndrome is a reversible hypothalamic disorder of a functional nature. PMID- 3346353 TI - Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the value of changes after short term triiodothyronine administration. AB - Thyroid hormone is one of several factors that modulate the level of sex hormone binding globulin (SHBG) in serum. SHBG levels are usually elevated in thyrotoxicosis and have been reported to be normal in a few patients with generalized resistance to thyroid hormone (GRTH). This study was designed to determine whether basal serum SHBG levels or the SHBG response to short term T3 administration could be used as an index of thyroid hormone action and thus serve as a test for the evaluation of patients suspected of having peripheral tissue resistance to thyroid hormone. Serum SHBG, total T4, free T4 index (FT4I), total T3, and TSH levels were measured in 21 normal subjects, 28 hypothyroid patients, 20 thyrotoxic patients, and 10 patients with GRTH. Excluding patients with GRTH, serum basal SHBG values were correlated with FT4I values (r = 0.66; P less than 0.0001). Mean SHBG levels in the patients with GRTH [37.6 +/- 16.2 (+/- SD) nmol/L] were not significantly different from those in the normal subjects (35.1 +/- 19.3 nmol/L) or hypothyroid patients (26.3 +/- 17.1 nmol/L), but were significantly lower than those in the thyrotoxic group (64.7 +/- 19.2 nmol/L; P less than 0.001). All 10 patients with GRTH had basal SHBG values in the normal range, but 7 of 20 (35%) thyrotoxic patients also had normal basal SHBG values. T3 was given orally for three sequential 3-day periods at doses of 50, 100, and 200 micrograms daily to 7 normal subjects, 11 hypothyroid and 3 thyrotoxic patients, and all 10 patients with GRTH. The serum SHBG concentration was measured on the last day at each dosage level. During T3 administration, SHBG levels increased in all individuals with normal tissue responsiveness. The increase above the basal value (delta SHBG) at each T3 dose was similar in normal, hypothyroid, and thyrotoxic individuals (non-resistant subjects). After administration of 50 micrograms T3 daily, the mean delta SHBG level was decreased [-2.9 +/- 5.3 (+/- SD) nmol/L] in the resistant patients and increased (4.0 +/- 4.9 nmol/L; P less than 0.005) in the nonresistant subjects. After administration of 100 micrograms T3 daily, the mean delta SHBG was -4.5 +/- 6.8 nmol/L in the resistant patients and 8.6 +/- 5.1 nmol/L (P less than 0.0001) in the nonresistant subjects. Serum SHBG decreased by more than 2 nmol/L in 6 of 10 (60%) resistant patients, but in no nonresistant subject.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346354 TI - A mutation of the androgen receptor associated with partial androgen resistance, familial gynecomastia, and fertility. AB - A family is described in which gynecomastia and undervirilization in five men (four of whom have fathered children) were inherited in a manner compatible with an X-linked defect. Three members from whom blood could be obtained had supranormal serum testosterone and normal LH and FSH levels. One man had severe oligospermia with decreased motility, and one had normal sperm density and motility. In fibroblasts cultured from genital skin biopsies from two of the men, the levels of androgen receptor and affinity of binding of receptor to dihydrotestosterone were normal. However, androgen binding in fibroblast monolayers was thermolabile, up-regulation of receptor levels did not occur after prolonged incubation of monolayers with dihydrotestosterone or methyltrienolone, and dissociation rates at 37 C were increased with the synthetic androgen mibolerone. In addition, in cytosol preparations the androgen receptor protein was unstable. This disorder probably represents the most subtle functional abnormality of androgen receptor characterized to date, since it is compatible with normal male phenotypic development and in some affected men with fertility. It follows that infertility is not an invariable feature of androgen resistance as we previously suggested. PMID- 3346356 TI - Increased luteinizing hormone pulse frequency during sleep in early to midpubertal boys: effects of testosterone infusion. AB - Gonadotropin secretion is pulsatile in prepubertal and early pubertal boys, and the onset of puberty is characterized by a sleep-associated rise in LH pulse amplitude. To determine whether an augmentation in LH pulse frequency as well as amplitude occurs at the onset of puberty, we studied gonadotropin secretion in 21 early to midpubertal boys. Blood samples were taken every 20 min (every 15 min in 4 boys) for LH determinations. A 2-fold increase in LH pulse frequency occurred during the nighttime sampling period (2200-0400 h) compared to that in the hours when the boys were awake (1000-2200 h). The maximum frequency (0.7 pulses/h) occurred between 2400 and 0200 h. The mean plasma LH concentration increased during the night from 2.3 +/- 0.2 (+/- SE) mIU/mL (2.3 +/- 0.2 IU/L) between 2000 2200 h to a maximum of 6.2 +/- 0.4 (6.2 +/- 0.4 IU/L) between 0200-0400 h. The mean plasma LH decreased to 5.5 +/- 0.4 mIU/mL (5.5 +/- 0.4 IU/L) between 0400 0600 h and to 4.2 +/- 0.5 (4.2 +/- 0.5 IU/L) between 0600-0800 h. Plasma testosterone rose during the night to a mean maximum value of 2.4 +/- 0.5 (+/- SE) ng/mL (8.3 +/- 1.7 nmol/L). This finding suggested that the rise in testosterone might play a role in decreasing LH secretion during the later hours of sleep (after 0400 h). To address this question and to study further the effects of testosterone in early puberty, we measured plasma LH concentrations every 10 min from 2000-0800 h in 8 early to mid-pubertal boys before and during short term testosterone administration. Saline or testosterone at a concentration of 9.33 micrograms/mL (32 mumol/L) was infused at a rate of 10 mL/h from 2100 1200 h to shift the nighttime testosterone rise 3 h earlier than would occur spontaneously. Blood samples were obtained every 10 min for LH and every 30 min for testosterone determinations from 2000-0800 h. Pituitary responsiveness was assessed by administering sequential doses of synthetic GnRH (25 and 250 ng/kg) at 1000 and 1200 h, respectively. The nighttime increase in LH pulse frequency and mean plasma LH concentration occurred between 2300 and 0200 h despite testosterone infusion. However, testosterone infusion was associated with significantly lower mean plasma LH concentrations from 0200-0800 h compared to those on the night of the saline infusion. Pituitary responsiveness to synthetic GnRH was unaltered by testosterone administration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346355 TI - Effects of amiodarone therapy on thyroid iodine content as measured by x-ray fluorescence. AB - Thyroid iodine content (TIC) was measured by x-ray fluorescence in 68 patients who had received amiodarone treatment for varying intervals (1 g/week for 1-120 months). Thirty-six patients were euthyroid; the mean TIC of the patients (n = 15), who had been treated for less than 12 months was 30 +/- 19 (+/- SD) mg, twice the normal mean value (14.6 +/- 5.0 mg), and it was 39 +/- 17 mg in those (n = 16) who had been treated for 12-60 months and 29 +/- 6 mg in those (n = 5) who had been treated longer (greater than 60 months). Nineteen patients were hyperthyroid and had elevated TIC values. Of them, 6 patients had a goiter; their TIC (50 +/- 19 mg) was not significantly different from that of the hyperthyroid patients with no goiter (55 +/- 29 mg), but they became hyperthyroid more rapidly. Thirteen patients were hypothyroid; none had TIC values above the normal range, and it was below 2.5 mg in 5 patients. A sequential study was undertaken in 11 euthyroid patients who had no detectable antithyroid antibodies. TIC did not increase during treatment in 2 patients; both developed hypothyroidism, which was transient in 1 despite continuation of amiodarone treatment. The TIC initially increased during amiodarone treatment in the other 9 patients, leveling off at the end of the first year. The TIC rose well above the upper limit of the normal range in 4 patients, of whom 2 became hyperthyroid during the second year of treatment. TIC remained within the normal range in the other 5 patients, of whom 3 became hypothyroid after 12-24 months of treatment (1 subclinical, 2 overt). Although the TIC was significantly higher in the patients with hyperthyroidism than in the patients who remained euthyroid, the TIC test cannot be used to predict the occurrence of hyperthyroidism. The latter must be diagnosed on the basis of clinical symptoms and a frank elevation of serum thyroid hormone levels. Conversely, patients whose TIC values do not increase during treatment or remain within the normal range should be considered at risk for hypothyroidism. PMID- 3346357 TI - Quantitation of urinary somatomedin-C and growth hormone in preterm and fullterm infants and normal children. AB - Urinary GH and somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) excretion were measured in 12-h urine collections obtained from 43 infants (27 stable preterm infants and 16 healthy fullterm infants) and 31 normal children, aged 3 17 yr. Urinary Sm-C/IGF-I was excreted as the free hormone, since no binding of radiolabeled Sm-C/IGF-I to any urine protein with a mol wt similar to those described for plasma Sm-C/IGF-I-binding proteins was found. The preterm infants excreted significantly more urinary GH [13.5 +/- 2.1 (+/- SE) ng/kg.12 h] than either the fullterm infants (5.3 +/- 1.6 ng/kg.12h) or the children (0.27 +/- 0.02 ng/kg.12 h; P less than 0.01). The mean urinary Sm-C/IGF-I excretion in the preterm infants (98.9 +/- 7.5 mU/kg.12 h) was comparable to that in fullterm infants (87.6 +/- 9.7 mU/kg.12 h); both groups excreted significantly more urinary Sm-C/IGF-I than children (28.4 +/- 2.1 mU/kg.12 h; P less than 0.01). The group differences were similar when the results were expressed in terms of creatinine excretion. Urinary GH excretion correlated positively with urinary Sm C/IGF-I excretion (r = 0.68). The higher output of these peptides in rapidly growing infants and their positive correlation in urine provide additional support for the Sm hypothesis. PMID- 3346358 TI - Methionine-enkephalin and thyrotropin-stimulating hormone are intimately related in the human anterior pituitary. AB - The tissue distribution and function of opioid peptides in humans is incompletely defined. We report here that, unlike that in other species, the human anterior pituitary gland contains high concentrations of methionine-enkephalin (met enkephalin). The met-enkephalin immunoreactive material was isolated and identified as authentic met-enkephalin by fast atom bombardment-mass spectrometry and Edman degradation sequencing. The met-enkephalin was localized in a large subpopulation of TSH immunoreactive cells (thyrotrophs). No other proenkephalin derived opioid peptides were found in the pituitary, and there was no overlap between proopiomelanocortin and met-enkephalin immunoreactive cells. These results suggest that the human anterior pituitary gland contains a novel met enkephalin precursor and a possible role for met-enkephalin in regulating human thyroid function. PMID- 3346359 TI - Clomiphene citrate attenuates hyperprolactinemia associated with ovarian hyperstimulation in the primate menstrual cycle. AB - Exogenous human menopausal gonadotropin (hMG) therapy produces transient hyperprolactinemia during ovulation induction or ovarian hyperstimulation for in vitro fertilization, and hyperprolactinemia has been linked to decreased fertility. Coadministration of clomiphene citrate (CC) with hMG is often used to decrease the total amount of hMG used in such patients, but whether this results in less hyperprolactinemia is not known. As the hyperprolactinemia in this setting is a threshold phenomenon dependent on the strength and duration of estrogen exposure, we investigated whether CC acted as an estrogen to enhance PRL secretion or as an antiestrogen deterring estradiol (E2)- and progesterone (P4) induced hyperprolactinemia in nonhuman primates. Normally cycling (control) monkeys (n = 4) received E2 benzoate (12.5 micrograms/kg, im, daily) on menstrual cycle days 6-33 and continuous crystalline P4 via Silastic implants on days 20 33, a regimen known to initiate hyperprolactinemia. Treated monkeys (n = 5) received the same regimen, except that oral CC (15 mg daily) was given on days 6 33. Daily serum samples were assayed for E2, P4, and PRL. Both treatments caused significant (P less than 0.05) increases in serum PRL concentrations during P4 administration. The CC-treated monkeys had significantly smaller increases in mean PRL [21 +/- 1.5 (+/- SEM) vs. 44 +/- 6.3 ng/mL (micrograms/L); P less than 0.05] and smaller mean area under the PRL response curve [288 +/- 35 (+/- SEM) vs. 588 +/- 121 ng/day.mL (micrograms/day.L); P less than 0.05] than the control monkeys. We conclude that CC attenuates the hyperprolactinemia response to E2/P4 synergy in monkeys by acting as an antiestrogen. If coadministered with hMG for ovulation induction or ovarian hyperstimulation for in vitro fertilization, CC should attenuate hMG-induced hyperprolactinemia, thereby reducing its potentially adverse effects on fertility. PMID- 3346360 TI - 11 Beta-hydroxylase deficiency congenital adrenal hyperplasia: update of prenatal diagnosis. AB - Hormonal measurements in maternal urine and amniotic fluid (AF) during pregnancy and/or at delivery correctly predicted the postnatal diagnosis of 11 beta hydroxylase deficiency congenital adrenal hyperplasia (11 beta-OH deficiency CAH) in 7 fetuses at risk. In the 4 affected ones, maternal urinary tetrahydro-11 deoxycortisol (THS) excretion was high during the first trimester [0.3-2.2 mg/day (1.1-7.7 mumol/day)] and rose further during the third trimester [0.5-3.5 mg/day (1.8-12.3 mumol/day)] compared to urinary THS excretion in 20 normal pregnancies of the same gestational age (P less than 0.01). In 1 mother, dexamethasone administration (2 mg/day for 72 h) greatly reduced urinary THS excretion (and plasma steroid levels). Urinary THS excretion was low after delivery in these mothers, in normal pregnancies, and in parents of affected individuals [less than 0.05 mg/day (less than 0.08 mumol/day); P = NS]. However, 2 of the 3 heterozygous mothers who carried nonaffected fetuses excreted moderately increased amounts of THS during pregnancy, ranging from 0.15-0.26 mg/day (0.53-0.91 mumol/day), significantly higher than normal (P less than 0.01). Although urinary THS excretion in these mothers was similar to that in 2 mothers with affected fetuses early in pregnancy, urinary THS excretion was higher in mothers with affected compared to those with nonaffected fetuses after the first trimester (P less than 0.01). AF THS and 11-deoxycortisol concentrations were markedly elevated in pregnancies with affected fetuses (P less than 0.01), but normal in nonaffected ones. AF delta 4-androstenedione levels were high in 2 pregnancies and borderline elevated in a third. Although the AF tetrahydrocortisol and tetrahydrocortisone levels were always within the normal range, the AF THS to tetrahydrocortisol plus tetrahydrocortisone ratio was significantly elevated in all pregnancies with affected fetuses (2.8-5.5; P less than 0.01) and normal in nonaffected ones (0.48 1.2; P = NS) compared to that in 160 normal pregnancies [0.64 +/- 0.34 (+/- SD)]. AF 17-hydroxyprogesterone, testosterone, and 11-deoxycorticosterone levels were normal in all pregnancies. Maternal plasma 11-deoxycortisol and delta 4 androstenedione concentrations, determined sequentially throughout gestation, were variable and did not contribute to prenatal diagnosis. All affected infants were born hyperpigmented, 2 were large for gestational age, and the female was severely virilized. In the first week of life 2 males developed severe hypertension with seizures and adrenal insufficiency, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346361 TI - Human chorionic gonadotropin (hCG) and thyroid function in early human pregnancy: circadian variation and evidence for intrinsic thyrotropic activity of hCG. AB - To explore the diurnal variation and the relationship between serum hCG levels and thyroid function during pregnancy, 26 women with an uncomplicated early pregnancy were studied before and after interruption of pregnancy. The high serum hCG levels in early pregnancy were accompanied by an increase in serum thyroid hormone and a decrease in serum TSH levels. Nevertheless, serum TSH exhibited diurnal variation similar to that in nonpregnant women. The nocturnal surge of TSH exceeded the daytime nadir by 112% and was distinctly different from the normal serum cortisol variation. The diurnal serum T4 and hCG variations were similar to the variation in serum protein concentrations. After pregnancy interruption, serum hCG levels decreased by 95% within 10 days, and TSH levels rose concomitantly from 0.80 to 1.48 mIU/L (P less than 0.001). In individual women serum hCG correlated negatively with TSH (r = 0.322; P = 0.005) and positively with free T3 (r = 0.388; P less than 0.001). These results suggest that hCG has thyrotropic activity, which, through rises in thyroid hormone levels, suppresses TSH secretion. In this regard, 27,000-128,000 IU hCG correspond to 1 mIU TSH. Pregnancy-induced changes in thyroid function, however, do not affect the circadian TSH rhythm. PMID- 3346362 TI - Influence of low estrogen-containing oral contraceptives on lipoprotein phospholipid composition and mononuclear cell membrane fluidity. AB - Since the effects of the new low estrogen-containing oral contraceptive (OC) preparations on lipoprotein phospholipid (PL) composition are unknown, we studied 3 groups of 10 young women before and after 6 months of use of 3 commonly prescribed agents containing almost identical amounts of ethinyl estradiol (0.30 0.35 microgram) and differing progestogens, and correlated these changes with their estrogen to progestin (E/P) ratio. The directional changes in both plasma neutral lipid and PL concentrations tended to correlate with the E/P ratio, with plasma HDL-cholesterol (HDL-C) falling slightly and the low density lipoprotein cholesterol (LDL-C)/HDL-C ratio increasing in the women taking the OC with the lowest E/P ratio; in contrast, plasma HDL-C increased and the LDL-C/HDL-C ratio fell in those receiving the preparation with the highest E/P ratio. In HDL, the ratio of the 2 principal PL, sphingomyelin and lecithin, an index of lipid fluidity, tended to increase, suggesting that the surface of this lipoprotein class had become more rigid. This change was most apparent in women receiving the agent in which the progestin was predominant; in women receiving the preparations with the higher E/P ratios the sphingomyelin/lecithin ratio actually declined. The membrane fluidity of mononuclear cells obtained from five women taking an OC with a relatively high E/P ratio, however, was significantly increased (P less than 0.007) compared to that in normal women. These findings demonstrate that, even with substantial reductions in their estrogen content, the use of these newer OC is associated with quantitative and qualitative changes in lipoprotein PL composition that parallel their E/P balance and are associated with altered fluidity of mononuclear cell membranes. PMID- 3346363 TI - Pathological hyperprolactinemia suppresses hot flashes in menopausal women. AB - Hyperprolactinemia impairs pituitary-gonadal function in young women, but its effect in menopausal women is not known. The purpose of this report is to describe the effect of hyperprolactinemia on gonadotropin secretion and hot flashes in menopausal women before and after treatment with a dopamine agonist. We studied two such women with prolactinomas. Both had plasma LH and FSH levels in the range found in premenopausal women and no hot flashes. Treatment with bromocriptine was associated with normalization of plasma PRL levels, elevation of plasma gonadotropin levels, and the onset of menopausal hot flashes in both patients. We conclude that hyperprolactinemia can inhibit the augmented gonadotropin secretion that occurs in postmenopausal women and prevent hot flashes. PMID- 3346364 TI - Failure of maintained hyperprolactinemia to improve lactational performance in late puerperium. AB - Although stimulation of PRL secretion in the early postpartum period has been found to improve lactational performance, the effect of chronic maintenance of elevated plasma PRL levels on milk production is not known. In a randomized design, 66 lactating women were assigned to receive either a placebo (n = 32) or the dopamine antagonist sulpiride (n = 34; 100 mg, three times daily), for 4 days, followed by 50 mg, three times daily, for a 90-day period). Their basal and 30 min postsuckling plasma PRL levels as well as the weights of their infants were measured 1, 4, 15, 30, 60, and 90 days postpartum. Forty-one women (20 sulpiride-treated and 21 placebo-treated) completed the study. Compared with the placebo group, which had the expected postpartum plasma PRL decline, the sulpiride-treated women maintained significantly elevated basal plasma PRL values up to the 90th postpartum day. In contrast, the postsuckling plasma PRL level was significantly diminished in the latter group, and on day 90 was practically absent. On day 15, weight gain was significantly greater in the infants whose mothers received sulpiride, but later, no differences were detectable between groups of infants despite the disparity in PRL levels in their mothers. We conclude that enhancement of PRL secretion in the early postpartum period may transiently increase milk production, but chronic hyperprolactinemia has no effect on lactational performance. The plasma PRL response to suckling is not essential for the maintenance of milk secretion. Instead, basal plasma PRL levels and neurogenic reflexes may be more instrumental in maintaining established lactation. PMID- 3346365 TI - Hashimoto's thyroiditis with a monoclonal antithyroglobulin autoantibody: disappearance of the monoclonal antibody after thyroidectomy. AB - A 46-yr-old man had typical Hashimoto's thyroiditis (HT) and a serum monoclonal immunoglobulin (MIgG kappa). There was no evidence of disseminated lymphoid malignancy. Because of rapid enlargement of the goiter with pressure symptoms, a total thyroidectomy was performed. The surgery was followed by the complete disappearance of the MIgG kappa paralleled by the disappearance of serum antithyroglobulin autoantibodies. Thyroid sections demonstrated HT. Direct immunofluorescence assay showed diffuse infiltration by lymphocytes and plasma cells that were mainly IgG kappa positive. Moreover, the serum MIgG kappa had antithyroglobulin activity, as demonstrated by two different methods, namely labeling of focused serum proteins with radioiodinated human thyroglobulin and immunoadsorption of the monoclonal IgG on a human thyroglobulin affinity column. These results demonstrate that a monoclonal antithyroglobulin autoantibody was produced within the thyroid in a patient with HT. As the production of a MIg is regarded as the last stage preceding the malignant transformation of normal B lymphocytes, this report strongly suggests that a B lymphoma can directly emerge from the intrathyroidal lymphocytes involved in the pathogenesis of Hashimoto's thyroiditis. PMID- 3346366 TI - Inhibin: definition and nomenclature, including related substances. PMID- 3346368 TI - In vitro interactions of serotonin (5-HT) with mononuclear cells from migraine patients: alterations related to the phase of the attack. AB - Serotonin (5-HT) binds in a saturable and specific manner to high affinity binding sites present on the surface of human mononuclear cells. The serotonin binding to mononuclear cells has been assayed in patients with migraine, during and outside the crisis period. In these patients, unlike the episodic cluster headache patients that show a constant trend, the results are variable. This variability may depend on the fluctuation of 5-HT levels in the blood, during and after the crisis. A possible explanation for these observations is that at the beginning of the crisis the binding of 5-HT is still similar to the normal level. As the crisis goes on, there is at first an increase in 5-HT binding that saturates all the available sites and a subsequent phenomenon of desensitization, with a loss of high affinity sites. Further investigations are needed in order to assess whether or not the mononuclear cell functions are affected by the modifications of the binding of 5-HT, thought to be a regulatory molecule. PMID- 3346367 TI - The effect of nerve growth factor and its antibody on mast cells in vivo. AB - Repeated subcutaneous administration of nerve growth factor (NGF) into newborn rats caused an increase in number and size of free and tissue-adherent mast cells (MCs). In vivo and in vitro autoradiographic studies show that MCs exhibit specific binding sites for NGF. Peritoneal MCs of adult rats exposed to high titers of endogenous (autoimmunization) and exogenous NGF antibodies showed severe cytological alterations and decreased in number. Light and electron microscopic studies revealed that MC destruction took place slowly (7-10 days) and required continual exposure to high titers of NGF antibodies. The role played by NGF in the hematopoietic cell lineage is at present under study in our laboratory. PMID- 3346369 TI - Autoantibodies in paraneoplastic cerebellar degeneration bind to cytoplasmic antigens of Purkinje cells in humans, rats and mice and are of multiple immunoglobulin classes. AB - Purkinje cell autoantibodies in sera of six female patients with paraneoplastic cerebellar degeneration (PCD) were investigated by indirect immunofluorescence for immunoglobulin isotype and species specificity. Four patients had gynecologic cancer, one breast cancer and one lymphoma. Control sera from 125 patients were negative for Purkinje cell antibodies of IgG, IgM and IgA isotypes. These included neurologically normal cancer patients, cancer patients with paraneoplastic syndromes not involving the cerebellum and patients with non neoplastic neurologic disorders. IgG antibodies in the six PCD sera bound to discrete cells in the cerebellum of human, rat and mouse (titers 1000-128,000). Antibodies of IgM class were additionally found in two sera (titers 100 and 500) and IgA in a third serum (titer 1000). Antibodies of each isotype gave a similar staining pattern, highlighting the cytoplasm of Purkinje cells in a coarse granular pattern, and the peripheral cytoplasm of discrete molecular layer cells. Antibodies of IgE class were not found. Rodent cerebellar tissue was found to be a useful substitute for human tissue in clinical testing for Purkinje cell antibodies, and has the advantage of being readily available in highly viable state. Its use should facilitate further characterization of the autoantigen(s) of PCD, and possibly the development of an animal model involving passive transfer of immunoglobulins. Screening for IgM and IgA Purkinje cell antibodies in addition to IgG may increase the yield of positive results in clinical serological testing. PMID- 3346370 TI - Identification of synaptic terminals of thalamic or cortical origin in contact with distinct medium-size spiny neurons in the rat neostriatum. AB - In order to determine what types of neurons in the striatum receive direct synaptic input from corticostriatal and thalamostriatal fibres and whether these afferents converge on individual striatal neurons, double anterograde labelling of axon terminals was combined with Golgi impregnation at both the light and electron microscopic levels. The area of the central neostriatum that receives input from both the parafascicular nucleus of the thalamus and the somatosensory cortex was identified by retrograde transport of a conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA). The same region of the neostriatum was studied in rats that had received multiple electrolytic lesions in the somatosensory cortex and also an injection of HRP-WGA in different parts of the parafascicular nucleus. Sections of this part of the neostriatum were impregnated by the single-section Golgi procedure after revealing anterogradely transported HRP-WGA. Twelve Golgi-impregnated spiny neurons were recovered and examined in the light and electron microscope after gold-toning. Ten of these neurons were typical very densely spiny medium-size neurons and they were all found to receive asymmetric synaptic input on dendritic spines from degenerating corticostriatal boutons. However, even though numerous boutons labelled anterogradely by HRP-WGA from the parafascicular nucleus were found within the dendritic fields of neurons that received cortical input, none of the terminals from the thalamus made synaptic contact with these neurons. Instead, all 96 thalamostriatal boutons studied were found in asymmetric synaptic contact with dendritic shafts of other neurons. Two such neurons that received input from the parafascicular nucleus were Golgi-impregnated and appeared to be medium-size spiny neurons, but they had a lower density of spines than the typical very densely spiny neurons. An independent confirmation that the targets of thalamostriatal neurons originating in the parafascicular nucleus are dendritic shafts was provided by studying the boutons labelled following electrolytic lesioning or injection of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) into this nucleus: these boutons were also found to form asymmetric synaptic contacts with dendritic shafts within the neostriatum. It is concluded that although afferents from the somatosensory cortex and from the parafascicular nucleus converge upon the same part of the neostriatum, they probably do not converge upon the same spiny neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346371 TI - Role of visual experience in promoting segregation of eye dominance patches in the visual cortex of the cat. AB - Transneuronal autoradiography was used to study the role of visual experience in the development of ocular dominance patches in the cat. In order to assess quantitatively the effects of visual deprivation, image analysis was used to measure the profiles of grain density in layer IV. Fourier power spectra of these profiles were computed to give a measure of the amplitudes and frequencies of the fluctuations in grain density that were present. Deprivation of normal patterned vision by binocular lid suture or by rearing in total darkness from shortly after birth abolished the dominant periodicity (of about 1.1 mm) in the distribution of left and right eye afferents in layer IV of area 17. A dominant periodicity of about 2.2 mm was, however, present in area 18 of both normal and dark-reared animals. Visual deprivation was not able to reverse segregation. One animal reared normally for 6 weeks was placed in the dark for a further 28 weeks and showed normal periodicities in the distribution of geniculate inputs to area 17. Another animal given 128 hours of experience and kept in the dark for the rest of the time until it was 12 weeks old also showed normal segregation. To determine the minimum amount of visual experience necessary for segregation to occur, four animals were given 8-, 24-, 48-, and 128-hour periods of visual experience and were studied at 12 weeks of age. Eight hours of experience had no detectable effect on segregation; periodicities of intermediate amplitude were present in animals that received 24 and 48 hours of experience, while 128 hours of experience resulted in periodicities of normal amplitude. Recovery from visual deprivation was studied by rearing kittens from birth in the dark for varying periods and then returning them to the normally lit colony room for periods of 6 to 22 weeks. Recovery from 6 weeks of dark rearing was found to be complete; much less recovery occurred following periods of 8 to 25 weeks of initial deprivation, and no recovery at all occurred after 30 weeks of deprivation. It is concluded that the spontaneous activity present in the geniculocortical afferents of dark reared and lid-sutured cats is not adequate to drive normal periodic segregation in area 17, though it can do so in area 18. Between 48 and 128 hours of visual experience, given before 8 weeks of age, appears to be necessary and sufficient for normal periodic segregation of geniculate afferents in area 17 of the cat. PMID- 3346372 TI - Distribution and morphological characteristics of dopamine-immunoreactive neurons in the midbrain of the squirrel monkey (Saimiri sciureus). AB - The distribution and morphological characteristics of dopamine (DA) neurons in the midbrain of the squirrel monkey (Saimiri sciureus) were investigated by peroxidase-antiperoxidase (PAP) immunohistochemistry with a highly specific antiserum raised against DA-glutaraldehyde-lysyl-protein conjugate (donated by M. Geffard). Four contiguous areas contained DA-immunostained nerve cell bodies: (1) the substantia nigra, pars compacta (SNc), (2) the ventral tegmental area (VTA), (3) the retrorubral area (RRA), and (4) the periaqueductal gray (PAG). The SNc composed the vast majority of DA-immunostained neurons. Most of these neurons were relatively large (mean diameters: 35 x 15 micron) and varied in shape from fusiform to polygonal, but a few smaller (16 x 10.5 micron) globular cells were dispersed among them. The caudal two-thirds of the SNc was particularly rich in DA somata. Rostrally, these DA cells formed several distinct columns impinging deeply upon the underlying pars reticulata. Large oval sectors mostly devoid of immunoreactivity were delineated by these trabeculae. The long dendritic processes of DA neurons in the SNc were generally oriented in prominent dorsoventral bundles the ventralmost portion of which arborized diffusely along the dorsal surface of the cerebral peduncle. In the VTA, the DA neurons were regrouped in a triangular zone located dorsal to the interpeduncular nucleus, medial to the substantia nigra and ventral to the oculomotor nucleus. These DA cells were of medium size (19 x 10.5 micron), globular or fusiform, and usually showed one or two thick primary dendrites oriented dorsoventrally. The DA cells in the RRA lay in continuity with the most caudal DA-containing elements of the substantia nigra but could be distinguished by their smaller size (26 x 12 micron), shorter and more profusely branched dendrites, and darker immunostaining. These DA neurons were characteristically scattered among and medial to the fibers of the medial lemniscus, and a few could be observed as far caudally as the pedunculopontine nucleus. In the PAG, DA-immunostained neurons were seen in the rostral half of the mesencephalic central gray and predominated in its ventral half. These cells were of medium size (22.5 x 10 micron) and some of them were found in proximity to the ventricular lining. At caudal levels, the DA-positive cells in the PAG did not intermingle with dorsal raphe neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346373 TI - Cell death in the inner and outer nuclear layers of the developing cat retina. AB - The occurrence and distribution of pyknotic profiles (dying cells) in the inner (INL) and outer nuclear layers (ONL) were mapped from radial sections through 13 kitten retinae aged from the 30th postconceptional day (30PCD) to the 81PCD (17th postnatal day). Cell death in the INL occurs in two consecutive waves, each beginning at the area centralis and proceeding toward the retinal edge. The first wave involves cells located in the inner part of the INL, adjacent to the inner plexiform layer. It begins on the 50PCD and lasts until the 66PCD, with a peak of 72,000 profiles on the 58PCD. This wave of cell death seems to be associated with the formation of the inner plexiform layer and may be due to the elimination of amacrine cells which have failed to establish sustaining connections with their appropriate target cells. The second wave involves cells located in the outer part of the INL, adjacent to the outer plexiform layer. It begins on the 60PCD and lasts until after the 81PCD, with a peak of 65,000 on the 71PCD. This wave appears to be due to the elimination of ectopic photoreceptor cells displaced by the formation of the OPL and presumably prevented from establishing sustaining connections with their appropriate target cells. A phase of cell death in the ONL begins on about the 42PCD and lasts until after the 81PCD, with a peak of 10,300 pyknotic profiles on the 60PCD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346374 TI - GABA-like immunoreactivity in the pedal ganglia of Mytilus galloprovincialis: light and electron microscopic study. AB - The distribution of gamma-aminobutyric acid (GABA)-like immunoreactivity was investigated in the pedal ganglia (PG) of Mytilus galloprovincialis (Mollusca, Bivalvia) with the aid of an antiserum raised against GABA coupled to bovine serum albumin. Examination of whole-mount preparations and serial vibratome and semithin sections showed the presence of different types of immunoreactive neurons. Small unipolar neurons were the most numerous, and were located mainly in the lateral ganglion cortex. A few bipolar and small multipolar neurons were scattered in the cortex, and, more rarely, in the neuropile. Furthermore, two large symmetrical multipolar neurons, the processes of which extended over large fields in the ipsilateral and contralateral neuropile, were consistently observed in each ganglion. Immunoreactive fibers formed networks in the neuropile and ran parallel in the commissure and in all nerves and connectives. The morphology and distribution of neurons and fibers immunostained by the anti-GABA serum were similar to those of GAD-like immunoreactive elements, which indicates that the neurotransmitter and its biosynthetic enzyme are present in the same neurons. Moreover, comparison of serial semithin sections alternatively incubated in postembedding with anti-GABA and antiserotonin sera revealed that immunoreactivity for these two substances was present in different neuronal populations. However, close association between serotoninlike and GABA-like immunoreactive elements was observed in a few PG areas. GABA-like immunoreactivity was demonstrated on ultrathin sections by using secondary antiserum coupled to colloidal gold particles. Labeling was found over somata, fibers, and varicosities containing a distinct type of small (63 nm), pleomorphic, dense-cored vesicle. PMID- 3346375 TI - Topography and organization of cranial nerve nuclei in the sand lizard, Lacerta agilis. AB - Cobaltic-lysine complex compound was used to label cranial nerves of the ventrolateral (branchiomotor) and dorsomedial (somatomotor) nuclear columns in the sand lizard, Lacerta agilis. The dendritic arborizations and axonal trajectories of neurons of the respective nuclei were reconstructed from serial sections. A fairly uniform neuronal morphology was found in the nuclei of the ventrolateral column: a spindle-shaped perikaryon gave rise to dorsomedial and ventrolateral dendritic trees, the latter arborizing in a characteristic broomlike manner within a narrow region in the lateral white matter. Axons of all neurons converged upon the medial longitudinal fasciculus and after making a hairpin turn formed the corresponding motor roots. A group of small neurons constituted a separate subnucleus within the V motor nucleus. The VII and IX nuclei were fused into a single nuclear complex. The nucleus ambiguus was found dorsal to the XII nucleus and lateral to the dorsal vagal nucleus. The latter nucleus extended rostrally to the caudal pole of the VI nucleus, and its neurons sent axons to the VII, IX, and X nerves. The term "dorsal visceromotor column" designates the extended dorsal vagal nucleus. A number of small polygonal neurons lying scattered in the lateral part of the medulla were labeled via the VII, IX, and X nerves. This loose aggregate of labeled neurons was termed the "lateral visceromotor area." On the basis of nuclear topography and cellular morphology, the existence of a bulbar XI nucleus was excluded. Three different types of neurons could be distinguished in the dorsomedial nuclear column. Neurons with oval or spherical perikarya and radially oriented dendrites constituted the nuclei innervating external eye muscles. Except for the IV nucleus, axons followed a ventral trajectory. The accessory VI nucleus was composed of a second type of neuron with elongated soma and dorsoventral dendrite orientation; the dorsally directed axon turned ventrally at the VI nucleus. The XII nucleus contains a third type of neuron with strongly decussating dendrites. The distinct differences in the neuronal morphology did not support the classical assumption that all of the nuclei of the dorsomedial motor column supply muscles derived from somitic mesoderm. Sensory fibers of the trigeminal nerve formed the familiar spinal tract, which partially decussated in the medullospinal transition zone and could be followed as far as the lumbar segments on the ipsilateral side of the spinal cord. Neurons of the mesencephalic root of the trigeminal nerve were localized in the optic tectum; their descending fibers joined the medial aspect of the spinal tract.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346376 TI - Topologic and connectional analysis of the dorsal thalamus of Triturus alpestris (amphibia, urodela, salamandridae). AB - A morphological and connectional analysis was performed on the dorsal thalamus of the alpine newt, Triturus alpestris. We have used a graphic reconstruction technique for the evaluation of the connectional (HRP) data. On the basis of these reconstructions, we propose a subdivision of the salamandrid dorsal thalamus into subhabenular, anteroventral, and posterodorsal zones. Each of these zones is defined by its telencephalic projections ("ascending thalamofugal systems"). The posterodorsal zone projects to the striatum, the anteroventral zone to the pallium. The subhabenular zone projects to the subpallial telencephalon and to the tegmentum. This zonal subdivision allows a more detailed comparison of the salamandrid dorsal thalamic features with ranid dorsal thalamic structures. We compare our dorsal thalamic zones to the ones proposed by Herrick (J. Comp. Neurol. 62:239-261, '35, The Brain of the Tiger Salamander. Chicago: The University of Chicago Press, '48). Furthermore, using the same reconstructive technique, we undertook an analysis of the spatial relations of various inputs to the salamandrid dorsal thalamus ("thalamopetal systems"). Besides the well-known retinal inputs, we identified the tectum and the tegmentum as sources of inputs to the thalamus. We provide evidence that there is no extensive multi- or unimodal overlap of these thalamopetal systems. PMID- 3346377 TI - Organization and efferent connections of transplanted suprachiasmatic nuclei. AB - The hypothalamic suprachiasmatic nucleus (SCh) is the principal brain structure involved in the generation of circadian rhythms. In the present study, we have employed immunohistochemical techniques to evaluate the development of the fetal SCh following its transplantation to the brain of adult host animals. Donor hypothalami were obtained from normal Long-Evans fetuses and transplanted to the lateral, third, or fourth ventricle of Brattleboro rats. Neuronal aggregations exhibiting the organotypic features of the SCh were present in over 90% of the grafts recovered at each transplantation site. Like the normal endogenous SCh, SCh-like cell groups identified within the transplants contained a prominent population of parvicellular (9-13 micron), neurophysin-containing neurons that were immunopositive for vasopressin (VP) but not oxytocin. These SCh-like cell groups also invariably contained similar small neurons that were immunoreactive for vasoactive intestinal polypeptide (VIP). Typically, VP and VIP immunoreactive perikarya were concentrated in contiguous, complementary parts of the grafted SCh, but fibers immunoreactive for either peptide were distributed throughout the extent of the nucleus. Because the brain of the Brattleboro rat is deficient in vasopressin, it was possible to evaluate the projection of the vasopressinergic component of the transplanted SCh to the host brain. Although SCh were identified in grafts recovered from each intraventricular transplantation site, an appreciable input to the host brain could be identified only when the fetal tissue was grafted to the third ventricle. Here, grafted SCh established efferent connections with periventricular diencephalic structures which ordinarily receive a projection from the in situ SCh. Specifically, VP immunoreactive fibers originating from transplanted SCh were identified in the medial preoptic area, the periventricular and dorsomedial hypothalamic nuclei, the paraventricular nuclei of the thalamus and hypothalamus, and in the retrochiasmatic area, arcuate nucleus, and suprachiasmatic nucleus of the host brain. These results demonstrate that the fetal SCh not only survives transplantation but also retains its distinguishing cytological features and the capacity to form an appropriately restricted set of efferent connections with the brain of adult host animals. PMID- 3346378 TI - Developmental changes in density and distribution of serotoninergic fibers in the chick spinal cord. AB - Developmental changes of serotoninergic innervation in the chick spinal cord (third lumbosacral segment) were examined with an immunohistochemical technique using an antiserum to serotonin. In the 1-day-old hatched chick, serotoninergic fibers were located in laminae I, II, VII, IX, and X. A large number of serotonin positive fibers and terminals were found around somal profiles of large neurons and in the neuropil of the medial and lateral parts of the lateral motor column (LMC). In the 1-week-old chick, the density of serotoninergic fibers was greatly increased in the posterior columns, and serotoninergic fibers were most densely aggregated in the dorsolateral part of the LMC. In the 2-week-old chick, a considerable decrease in the density of serotoninergic fibers was observed in the lateral funiculus and the gray matter (laminae I, II, VII, IX, and X). In the LMC, serotonin-positive fibers and terminals were largely absent from the neuropil, but were found preferentially around the somal profiles of large neurons. Between 1 and 2 weeks after hatching the density of varicosities and terminals in the neuropil of the dorsolateral and medial parts of the LMC decreased by 33% and 56%, respectively. In the 3-month-old chick, the density of serotoninergic fibers in laminae I, II, V, VII, and X had increased compared to younger ages. Serotonin-positive fibers were not evenly distributed in the LMC of the adult chicken; rather, they were densely aggregated around the soma and proximal dendrites of motoneurons in the dorsolateral LMC. Many neuronal soma in the medial and intermediate regions of the LMC lacked serotoninergic fibers. PMID- 3346379 TI - Chemosensory anterior dorsal fin in rocklings (Gaidropsarus and Ciliata, Teleostei, Gadidae): somatotopic representation of the ramus recurrens facialis as revealed by transganglionic transport of HRP. AB - The anterior dorsal fin in rocklings consists of a fringe of 50-80 delicate, vibratile rays, which are densely beset with epidermal chemosensory cells. The innervation of these cells is from the dorsal branch of the recurrent facial nerve, which also innervates all other fins and the skin of the trunk. This nerve carries at least three classes of fibres: small (0.5-1.5 micron in diameter), medium (1.5-4 micron), and large (greater than 4 micron). Approximately 12,000 small and weakly myelinated nerve fibres from the recurrent facial nerve innervate the anterior dorsal fin organ. Application of HRP at different locations of the recurrent facial nerve labelled three different sizes of sensory perikarya within the geniculate ganglion--small (6-15 micron in diameter), medium (18-24 micron), and large (greater than 25 micron)--which corresponds to the different size classes of fibres present within the nerve. Retrograde transganglionic transport of HRP revealed somatotopy within the brainstem facial lobe: the delicate nerve fibres innervating the chemosensory anterior dorsal fin terminate exclusively in a distinct, dorsal portion of the facial lobe. Fibres innervating the posterior dorsal fin, the anal and caudal fins, as well as the skin of the trunk terminate within caudal and dorsal areas of the ventral facial lobe; pectoral and pelvic fins are represented in the ventral and caudal portions of the ventral facial lobe. Innervation by a distinct type of fibre and exclusive representation within a distinct, dorsal part of the facial lobe may indicate a peculiar biological role in the anterior dorsal fin chemosensory organ in the rocklings. PMID- 3346380 TI - Remodeling of nerves during claw reversal in adult snapping shrimps. AB - Adult snapping shrimps, Alpheus heterochelis, undergo a reversal of their claw laterality following removal of the major claw, a process in which the existing minor claw transforms into a major and a new minor regenerates at the old major site. During such reversals the nerves to the ganglion are remodeled from one claw type to the other. Conversion of the nerves from the minor to the major type occurs within several days after removal of the contralateral major claw and involves the rapid addition of large numbers of sensory axons together with deletion of a few. Thus modeling of the nerves is essentially complete within the first intermolt in tandem with changes in the motoneurons but well ahead of changes in the muscle and external morphology. Conversion of the major nerves to the minor type is via massive degeneration of sensory axons during the first and second intermolts because of the loss of their peripherally located cell bodies. This is followed by proliferation of largely unmyelinated axons in the third intermolt, some of which become myelinated in the subsequent intermolts. Thus remodeling of the major nerves to minor, which is associated with the loss of a claw and the regeneration of a new minor claw, is a more traumatic and prolonged process compared to the remodeling of the minor nerves to major which is associated with the transformation of an existing claw. PMID- 3346381 TI - Anatomical connections of the prepositus and abducens nuclei in the squirrel monkey. AB - The primary goal of this investigation was to identify the areas of the brainstem and cerebellum that provide afferent projections to the nucleus prepositus hypoglossi in primates. After horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) was injected into the prepositus in squirrel monkeys (Saimiri sciureus), the largest populations of retrogradely labeled neurons were found in the vestibular nuclei, the contralateral perihypoglossal nuclei, and the medullary and pontine reticular formation. Unlike the cat, the prepositus in Saimiri received substantial projections from the nucleus raphe dorsalis and the central mesencephalic reticular formation, whereas few or no labeled cells were found in the cerebellar cortex, the superior colliculus, or the nucleus reticularis tegmenti pontis. By comparing the afferents to the prepositus with those to the abducens nucleus, we found that all regions projecting to the abducens also projected to the prepositus, without exception. Anterogradely transported WGA-HRP showed that the major brainstem recipients of prepositus efferents were the vestibular and perihypoglossal nuclei, the inferior olive, the medullary reticular formation, and the extraocular motor nuclei. In the cerebellar cortex, the prepositus projected to restricted regions of crura I and II as well as the caudal vermis and vestibulocerebellum. The many parts of the oculomotor system receiving input from the prepositus and the parallel innervation of the prepositus and the abducens by a large number of premotor centers lend support to the hypothesis that the prepositus may distribute an efference copy of motor activity, and may also play an important role in the process of neural integration. PMID- 3346382 TI - Light and electron microscopic immunocytochemical localization of parvalbumin in the dorsal lateral geniculate nucleus of the cat: evidence for coexistence with GABA. AB - The coexistence in individual neurons of parvalbumin and gamma-aminobutyric acid (GABA) was studied in the dorsal lateral geniculate nucleus (dLGN) of the cat using pre- and postembedding immunocytochemical methods. PV(+) cell bodies and processes were found in the perigeniculate nucleus (PGN) and throughout all laminae of the dLGN. PV(+) neurons were relatively small and had circular to fusiform shapes. Electron microscopy revealed PV(+) reaction product within the perikarya, axons, and dendrites of labeled cells. It was associated preferentially with microtubules, postsynaptic densities, and intracellular membranes. PV(+) presynaptic boutons were identified on the basis of their synaptic relations and ultrastructure as retinal terminals (RLP) and as profiles originating from inhibitory interneurons (F1 and F2). Immunopositive somata and dendrites received asymmetric synaptic contacts from labeled RLP and non identified, non-immunoreactive synaptic boutons. Moreover, PV(+) dendrites were postsynaptic to labeled F profiles. In the PGN all neurons were both PV(+) and GABA-immunoreactive and in the dLGN the vast majority of PV(+) neurons showed GABA-immunoreactivity. It is suggested that the high incidence of PV in GABAergic neurons is related to the particular activation patterns of these neurons and the resulting demand for calcium buffer systems. PMID- 3346383 TI - Intracortical connections and their physiological correlates in the primary auditory cortex (AI) of the cat. AB - We studied the functional and anatomical properties of the intrinsic connections in the primary auditory cortex (AI) of the cat by using physiological mapping and retrograde tracing methods. Our results revealed that a focal microinjection of tracer labeled as many as five intracortical patches in AI. The patches contained labeled pyramidal and non-pyramidal cell types, most of which were clustered in the middle layers. A densely distributed anterograde-like reaction product was present in the superficial layers above the labeled cells. The distribution of the patches was anisotropic, with most patches occurring dorsal, ventral, and anterior to the injection site. We examined the correlation between the characteristic frequency (CF) and binaural response properties of the injected and labeled regions. We found local labeling in regions possessing CFs equivalent to or slightly greater than that of the injected area. This appears to be a specific connection since we were able to predict the general location of many of the patches on the basis of the organization of the isofrequency domains. Patches were more numerous dorsoposterior to the injection site when the isofrequency contours ran obliquely (i.e., dorsoposterior to ventroanterior) across AI. The binaural response properties of the injected and labelled regions, however, were unrelated. PMID- 3346384 TI - Asymmetric distribution of retinal ganglion cells in goldfish. AB - The distribution of retinal ganglion cells (RGCs) in goldfish was determined by removing an eye and applying cobaltous-lysine to the optic nerve for 24 hr. This procedure allowed the cobalt label to be in continuous contact with the cut ends of the optic axons and thereby backfilled many RGCs. RGC density was determined across three different sizes of retinae by using fish with different eye sizes. Confirming earlier work, we found that RGC density diminished as retinal area increased. However, irrespective of the retinal size, the density of RGCs was elevated along the temporal boundary between the dorsal and the ventral retina. A conservative estimate indicated that the RGC density in the temporal retina was at least 1.8-2.5 times higher than the mean RGC density of the entire retina. Thus, the goldfish retina does not appear to have a homogeneous distribution of RGCs as was previously considered. Small and large retinae differed with respect to the percentage of cells in the RGC layer that was RGCs. In small retinae, even when the noncobalt-filled cells (glia and displaced amacrine cells) were added to the cobalt-filled RGCs, the density of all cell types was elevated in the temporal retina relative to the remainder of the retina. Furthermore, in small retinae, the percentage of cells in the RGC layer that was RGCs (75%) was constant across the radial and circumferential aspects of the retina. In marked contrast, in medium-large retinae, a homogeneous distribution of cells across the entire retina resulted when the noncobalt-filled cells were added to the cobalt filled cells. However, the percentage of cells that was cobalt-filled RGCs was significantly greater in the temporal retina (50%) than in the remainder of the retina (35%). In large retinae, as in small retinae, the percentage of cells that was RGCs did not vary as a function of distance from the optic disc. These data suggest that, in the course of retinal maturation, cell density in the temporal retina is elevated initially and then declines subsequently to the level of the surrounding retina. Over time, more displaced to the level of the surrounding retina. Over time, more displaced amacrine cells may be added to the tissue surrounding the temporal retina. Alternatively, more RGCs outside the temporal retina may become displaced amacrine cells. Such events could account for the growth-associated, disproportionate decrease in the percentage of cells that is RGCs in the tissue surrounding the temporal retina.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346385 TI - Taurine-like immunoreactivity in the brain of the honeybee. AB - Taurine (2-aminoethanesulfonic acid) is one of the most abundant free amino acids in the insect central nervous system. We have investigated the distribution of taurine-like immunoreactivity in the brain of the honeybee with an antiserum recognizing fixed taurine. Taurine-like immunoreactivity appeared within neuronal perikarya, neurites, and terminals, whereas glial cells were unlabelled. All photoreceptor cells of the compound eyes and the ocelli were stained. So were the fibers of the anterior superior optic tract, which connects the optic lobes to the mushroom bodies in the median protocerebrum. In the mushroom bodies the majority of intrinsic Kenyon cells showed high levels of taurine-like immunoreactivity. The lateral antennoglomerular tract, which interconnects the mushroom bodies with the antennal lobes, was also intensely stained. In the antennal lobes, strong labelling was observed within a few fibers that invade a set of posterior glomeruli from the posterior margin. Sensory projections from the antennal nerve into the antennal lobes showed only intermediate levels of staining. Sensory projections into the dorsal lobe were devoid of taurine-like immunoreactivity. Labral, mandibular, maxillary, and labial nerves, which innervate the various parts of the feeding apparatus, contain a set of five to eight heavily stained fibers. A comparison of taurine-like immunoreactivity with glutamate- and GABA-like immunoreactivities in the brain of the honeybee indicates that the three amino acids are enriched in distinct neuronal populations. PMID- 3346386 TI - Differences in synaptic inputs to preganglionic neurons in the dorsal and lateral band subdivisions of the cat sacral parasympathetic nucleus. AB - In the cat, preganglionic neurons (PGNs) found in the dorsal portion of the sacral parasympathetic nucleus (dorsal band or DB cells) participate in bowel control, while those found along the lateral edge (lateral band or LB cells) influence bladder function. In order to determine whether differences in the synaptic inputs exist between these two populations, HRP was applied to the sacral ventral rootlets of cats, and the S2 cord segment was prepared for sequential light and electron microscopy. When measured with light microscope, the LB somata had greater cross-sectional areas than did the DB cells. Ultrastructurally, the LB cells had a significantly greater percentage of their membrane apposed by synaptic active sites than did the DB cells. Also, the proximal dendrities of the labelled neurons received greater synaptic input than did the somata. No difference was found in the proportion of terminals containing dense cored vesicles (DCVs) when comparing LB and DB somata; however, the LB proximal dendrites had a higher proportion of their surface contacted by DCV containing terminals than did the DB dendrites. These ultrastructural results offer evidence that these two populations of preganglionic neurons differ with respect to their synaptic input as well as their peripheral targets. PMID- 3346387 TI - Central distribution of trigeminal and upper cervical primary afferents in the rat studied by anterograde transport of horseradish peroxidase conjugated to wheat germ agglutinin. AB - Injections of WGA-HRP were made in the rat trigeminal ganglion and C1-3 dorsal root ganglia (DRGs) to study the central projection patterns and their relations to each other. Trigeminal ganglion injections resulted in heavy terminal labeling in all trigeminal sensory nuclei. Prominent labeling was also observed in the solitary tract nucleus and in the medial parts of the dorsal horn at C1-3 levels, but labeling could be followed caudally to the C7 segment. Contralateral trigeminal projections were found in the nucleus caudalis and in the dorsal horn at C1-3 levels. The C1 DRG was found to be inconstant in the rat. When it was present, small amounts of terminal labeling were found in the external cuneate nucleus (ECN) and the central cervical nucleus (CCN). No dorsal horn projections were seen from the C1 DRG. Injections in the C2 DRG resulted in heavy labeling in the ECN, nucleus X, CCN, and dorsal horn, where it was mainly located in lateral areas. Labeling could be followed caudally to the Th 7 segment. C2 DRG projections also appeared in the cuneate nucleus (Cun), in all the trigeminal sensory nuclei, and in the spinal, medial, and lateral vestibular nuclei. A small C2 DRG projection was observed in the ventral cochlear nucleus. C3 DRG injections resulted in heavy labeling in both medial middle and lateral parts of the dorsal horn, in the ECN, and in nucleus X, whereas the labeling in the CCN was somewhat weaker. Smaller projections were seen to trigeminal nuclei, Cun, and the column of Clarke. Comparisons of the central projection fields of trigeminal and upper cervical primary afferents indicated a somatotopic organization but with a certain degree of overlap. PMID- 3346388 TI - Ultrastructural findings in idiopathic facial paralysis in the dog. AB - Unilateral facial paralysis of sudden onset is described in three dogs. Buccal nerve samples revealed widespread wallerian degeneration, and some attempts at regeneration. Regeneration was not sufficient to restore normal function. PMID- 3346389 TI - Desmin as a marker for canine botryoid rhabdomyosarcomas. AB - The intermediate filament desmin was present in three canine botryoid rhabdomyosarcomas. The use of desmin as a diagnostic tool may, as in these tumours in man, be of value in the classification of canine sarcomas where the origin of the tumour is not always apparent from routine histological sections. PMID- 3346390 TI - Intracellular iron storage and the pathogenesis of paratuberculosis. Comparative studies with other mycobacterial, parasitic or infectious conditions of veterinary importance. AB - The distribution of iron and mycobacteria was examined in the intestinal tract of ruminants with naturally-occurring M. paratuberculosis infection and compared with mycobacterial infections in several species. This distribution was compared with that of iron in chronic lesions caused by other microbial or parasitic agents. In the clinical form of paratuberculosis in cattle, sheep and goats there was marked lymphangiectasis and a high proportion of the granulomatous lesions contained siderotic macrophages with a high mycobacterial content. In cattle with preclinical lesions of granulomatous enteropathy, the greatest number of acid fast organisms was present in siderotic, non-differentiated, ileo-caecal macrophages; concurrent mast cell-associated allergic enteropathy was also apparent in the duodenum, proximal and mid-ileum of most animals. In paratuberculosis-affected herds, a high proportion of non-productive cows were without classical granulomatous change but had cultural or immunological evidence of M. paratuberculosis infection and similar allergic catarrhal enteropathy of the upper intestinal tract. Interstitial haemorrhage of the ileocaecal valve, with the accumulation of haemosiderin and ferritin in undifferentiated macrophages was observed in some of these cattle and also in others with experimentally-induced copper deficiency and acute ostertagiasis. Colonisation of the ileo-caecal or caecal glandular crypts by large, apparently saprophytic acid fast organisms indicated regional tolerance to such organisms in all cattle. In other mycobacterioses such as bovine or avian tuberculosis, undifferentiated, siderotic macrophages containing mycobacteria were also seen in early granulomas, but epithelioid and giant cell differentiation invariably led to the disappearance of intracellular iron and a reduction in mycobacterial numbers. In possums in which epithelioid and giant cells did not occur in response to M. bovis infection, siderosis persisted in many macrophages and overwhelming mycobacterial multiplication occurred. These studies indicate that, in most infections with mycobacteria, differentiation of macrophages radically reverses their iron acquisitive properties, creating an intracellular environment unsuitable for mycobacterial multiplication. It seems likely that allergically mediated microvascular haemorrhage, local tolerance of commensal mycobacteria and attenuation of the macrophage siderosis reversal mechanism provide unique conditions for early, uninhibited, intracellular multiplication of M. paratuberculosis in the ileo-caecal valve of certain mature ruminants. PMID- 3346391 TI - Pathological effects of carbadox in pigs with special emphasis on the adrenal. AB - Weaned pigs, 4-weeks-old, were divided into 6 groups of 13 animals each, which received 0, 25, 50, 100, 150 and 200 ppm (mg per kg) of carbadox medicated feed, respectively. After 5 and 10 weeks of carbadox administration, three and two pigs, respectively, of each group were necropsied. After 5 weeks treatment, gross lesions were seen in pigs receiving 50 ppm or more. The main features were retarded growth, dehydration with dry contents in the intestine, especially in the colon and findings suggestive of pica. The severity of lesions increased with higher dosages. After 10 weeks, the same changes, though much more pronounced, were observed at 100 ppm or higher dosages. After 5 weeks histological changes in the adrenals were found at 50 ppm treatment and upwards. The common feature was a hydropic appearance of the glomerular zone. In the 50 ppm group one out of three and, in the higher dosed groups, all pigs showed these changes. There was a dose response effect. At 100 ppm or more an enlargement of the glomerular zone was observed, resulting in narrowing of the fascicular layer. The adrenal capsule was slightly thickened and contained cells with PAS-positive granules. After 10 weeks, changes were found at 25 ppm dosage and higher. In the 25 and 50 ppm group half of the pigs had hydropic changes of the glomerular zone. In the higher dosed groups there were also chronic lesions. The outer part of the glomerular zone had become fibrotic. With 150 ppm or more the hydropic changes had extended into the fascicular layer, with development of hyperplastic nodules. This led to disappearance of zonal differentiation. From 100 ppm dosage, many richly granulated PAS-positive cells were present in the thickened capsule, more numerous and more granulated than after 5 weeks treatment. From this study, it can be concluded that carbadox may induce adverse effects on the adrenal in growing pigs at therapeutic (100 to 150 ppm) and feed-additive doses (50 ppm). Even at lower doses (25 ppm), mild lesions were found. The grade of lesions was positively correlated with the duration of exposure to this growth promoter. PMID- 3346392 TI - Early morphological changes in the striated muscles in normal and dystrophic chickens. AB - Histological and histochemical analyses were performed on the anterior latissimus dorsi muscle (ALD, red muscle) and the posterior latissimus dorsi muscle (PLD, white muscle) in normal (line 412) and dystrophic chickens (line 413) from 19 day embryos to 6 weeks of age. PLD, the white muscle, in dystrophic chickens showed higher percentages of red and intermediate fibres than those of normal chickens during the early development of muscles. Increases of the oxidative enzyme activities and the numbers of NADH--TR formazan granules in the white fibres of PLD were already found at 1 week of age in dystrophic chicken. Fibre types, oxidative enzyme activities and NADH--TR formazan granules showed no differences in ALD between normal and dystrophic chickens. These results suggest that increases of oxidative enzyme activities and formazan granule numbers and incomplete fibre type differentiation in PLD of dystrophic chickens are early pathological processes in such birds. PMID- 3346393 TI - Transmission of wildebeest-associated and sheep-associated malignant catarrhal fever to hamsters, rats and guinea-pigs. AB - Wildebeest-derived malignant catarrhal fever (WD-MCF) was transmitted to hamsters, rats and guinea-pigs by inoculation of rabbit lymphoid cells infected with alcelaphine herpesvirus-1, strain C-500. Sheep-associated MCF (SA-MCF) was transmitted to hamsters by inoculation of lymphoid cells from rabbits affected with SA-MCF derived from deer. Mice were refractory to both forms of the disease. With both forms of MCF, the incubation period during initial transmission varied from 21 to 90 days and disease was readily passaged in rodents by inoculation of live lymphoid cells. Clinical signs in hamsters most closely resembled those described for naturally occurring MCF. Results given here and in two following papers indicate that rodents are useful models to study the aetiology and pathogenesis of both forms of MCF. PMID- 3346394 TI - The pathology of wildebeest-associated malignant catarrhal fever in hamsters, rats and guinea-pigs. AB - Lesions typical of malignant catarrhal fever were found in hamsters, rats and guinea-pigs inoculated with a rabbit-passaged strain (C-500) of alcelaphine herpesvirus-1. Lesions found during primary passage included proliferation of lymphoid tissues, multisystemic mononuclear cell infiltrates, vasculitis and necrosis, especially in the alimentary tract. The character, severity and distribution of lesions remained stable in affected hamsters during serial passage of disease, whereas lympho-proliferation became dominant in rats. The lesions in rats typically affected lymph nodes, heart and kidney and appear similar to those caused by oncogenic herpesviruses. Because rodents are susceptible to malignant catarrhal fever, the prospect is advanced that they can be used to elucidate the pathogenesis of both lymphoproliferative and cytolytic aspects of the disease. PMID- 3346395 TI - Genital tumors: their management by micrographic surgery. AB - Genital tumors represent a special group requiring effective and curative treatment while functional and cosmetic demands require tissue sparing techniques. For these reasons, micrographic surgery is indicated. Over the past 5 years we have treated 24 such patients utilizing standard techniques for micrographic surgery. The patient population included twenty male and four female patients with ages ranging from 27 to 80 years. Histologically confirmed diagnoses included squamous cell carcinoma, Bowen's disease, verrucous carcinoma, basal cell carcinoma, Paget's disease, and leiomyosarcoma. These were located on the penis, scrotum, perineum, and buttocks. Seven of these patients were considered to have recurrent tumors. Preexisting conditions existed in 6 patients, including balantis xerotica obliterans, trauma, decubitus ulcer, and hidradenitis suppurativa. All surgery was performed under local anesthesia in the cutaneous surgery unit. Average pretreatment tumor size was 2.0 X 1.9 cm. Average postoperative defect size was 4.5 X 3.7 cm. Tumors were excised with an average of three stages and 18 sections. Most defects (65%) were allowed to heal by secondary intention, five (21%) were closed primarily, and three were referred for closure. After surgery five patients developed metastases in their regional lymphatic system. No patients developed local recurrence. Micrographic surgery is a most useful treatment modality in patients with genital tumors for control of local disease. However, patients with squamous cell carcinoma should be considered for elective regional lymph node biopsy and/or dissection in conjunction with micrographically controlled excision of the primary tumor. PMID- 3346396 TI - Are generic topical glucocorticosteroids equivalent to the brand name? PMID- 3346397 TI - Dapsone and rheumatoid vasculitis leg ulcerations. PMID- 3346399 TI - Acquired immunodeficiency syndrome (AIDS) can exacerbate psoriasis. PMID- 3346398 TI - Epidermolysis bullosa progressiva: a therapeutic suggestion. PMID- 3346400 TI - Traumatic plantar urticaria--an unrecognized entity? PMID- 3346401 TI - Delayed hypersensitivity to scopolamine in transdermal therapeutic systems. PMID- 3346402 TI - Late recurrence of cutaneous melanoma. PMID- 3346403 TI - Pruritus and cancer screening. PMID- 3346405 TI - May I be reviewed by a dermatologist? PMID- 3346404 TI - Reversible contraception for women at high risk of fetal anomalies. PMID- 3346406 TI - Yield from a complete skin examination. Findings in 1157 new dermatology patients. AB - A complete skin examination has been recommended by many dermatologists. The purpose of this study was to determine the yield of this examination. Of 1157 consecutively treated new dermatology patients, 1106 (96%) agreed to a total skin examination. Important incidental lesions were found in 162 (15%) of these patients. The types of incidental findings included (1) rashes helpful in establishing the primary diagnosis--20 patients (1.8%); (2) important rashes unrelated to the primary diagnosis--37 patients (3.3%); (3) malignant tumors--22 patients (2.0%); (4) clinically dysplastic nevi--25 patients (2.3%); and (5) congenital nevi--31 patients (2.8%). One patient had an incidental melanoma and another was found to have Kaposi's sarcoma, which led to the diagnosis of acquired immunodeficiency syndrome (AIDS). It is concluded that a complete skin examination is productive and it is recommended for all new dermatology patients. PMID- 3346407 TI - Subacute cutaneous lupus erythematosus-like drug eruption due to combination diuretic hydrochlorothiazide and triamterene. AB - Three patients taking a frequently prescribed diuretic combination of hydrochlorothiazide and triamterene developed eruptions resembling subacute cutaneous lupus erythematosus. Histopathology of the skin biopsies of all three patients was consistent with subacute cutaneous lupus erythematosus. On discontinuation of the diuretic drug, the cutaneous eruptions cleared. PMID- 3346408 TI - The case for patch test readings beyond day 2. Notes from the lost and found department. AB - Additional patch test readings taken after 2 days (48 hours) are valuable in distinguishing false-positive reactions, which may occur up to 22% of the time. Second readings taken on days 3 through 7 may detect an additional 34% positive reactivity. Those reactions, both lost (initially positive, later negative) and found (initially negative, later positive) by delayed readings, require clinical correlation for relevance as do the readings that persist at and beyond day 2 (positive at both readings). PMID- 3346409 TI - Antithrombotic treatment in livedo vasculitis. AB - Two patients with livedo vasculitis were treated successfully with antiplatelet drugs including ticlopidine hydrochloride, dipyridamole, and low-dose aspirin. Increased platelet functions were restored 1 week after the beginning of the treatment, followed by dramatic improvement of painful leg ulcers within 1 month. Livedo status was unchanged. We claim that antiplatelet therapy should be the first choice of treatment in this disease. PMID- 3346410 TI - Effect of pH on the production of irritation in a chamber irritation test. AB - This study was designed to investigate the relationship between alteration of skin surface pH and the development of skin irritation. Application of a phosphate/borate/acetate buffer adjusted to pH 4.0-10.5 in a standard chamber irritation test did not result in significant clinical irritation. This was true in spite of maintaining a markedly altered skin surface pH over an extended period of time. There was also no correlation between irritation and the pH of applied surfactant solutions. These results demonstrate that a prolonged disturbance of the "acid mantle" is not sufficient to produce clinical irritation. PMID- 3346411 TI - Actinic lichen planus mimicking melasma. A clinical and histopathologic study of three cases. AB - Three cases of actinic lichen planus mimicking melasma are presented. Although the clinical similarity to melasma is striking, the histopathologic picture is distinctive. It is suggested that actinic lichen planus be considered in the differential diagnosis of melasma. PMID- 3346412 TI - Improvement of psoriasis vulgaris after intralesional injections of 15 hydroxyeicosatetraenoic acid (15-HETE). AB - Psoriatic skin lesions are characterized by elevated levels of 5- and 12 lipoxygenase products (leukotrienes B4, C4, and D4, and 12 hydroxyeicosatetraenoic acid [12-HETE]), which can stimulate epidermal proliferation and induce skin inflammation. 15-Hydroxyeicosatetraenoic acid (15 HETE) has the potential to inhibit the activity of 5- and 12-lipoxygenases. The purpose of the present study was to determine the therapeutic effect of intralesional injections of 15-HETE. 15-HETE was formed by oxidation of arachidonic acid by soybean lipoxygenase, purified by reversed-phase high performance liquid chromatography, and identified by mass spectrometric analysis. Thirteen patients took part in the investigation. Plaques with a diameter of approximately 1 cm were injected with 0.1 ml of 10 mumol/L 15-HETE, 0.1 ml of 1 mumol/L 15-HETE, or 0.1 ml of saline weekly. After 3 weeks the effect was evaluated clinically and histologically by an observer uniformed of the treatment given. We found that plaques injected with 10 mumol/L 15-HETE had cleared completely in four patients and improved considerably in seven. In one patient minimal improvement only was seen and in one patient no change was observed. Injection of 1 mumol/L 15-HETE was without effect in 11 patients and improvement was observed in two patients. Of the plaques injected with saline, minimal improvement was observed in one patient; otherwise the plaques had not changed. Injection of 0.1 ml of 10 mumol/L 15-HEPE (identical to 15-HETE except for five double bonds instead of four) induced only minimal improvement in one of four patients. The results imply that 15-HETE by a dose-dependent and stereospecific mechanism can improve psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346413 TI - Cancer of the skin in blacks. V. A review of 175 black patients with squamous cell carcinoma of the penis. AB - Histologically diagnosed squamous cell carcinoma of the penis in black patients was reviewed through the Tumor Registry of Charity Hospital covering the years 1948 to 1985. There were 175 cases, including 15 cases of squamous cell carcinoma in situ. The overall mortality was 15.4%. Associated second primary malignancies, almost all of which were found after the diagnosis of squamous cell carcinoma of the penis, occurred in 17.7% of the patients. PMID- 3346414 TI - Ultrastructural morphometric analysis of lesional skin: mast cells from patients with systemic and nonsystemic mastocytosis. AB - Lesional skin mast cells from some patients with mastocytosis appear morphologically atypical; however, these subjective differences have not been quantified. Herein we describe an objective method for analyzing cutaneous mastocytosis mast cells by a combination of morphometric analysis and electron microscopy. By this technique, lesional mast cells from patients with adult systemic mastocytosis had a significantly larger mean cytoplasmic area (53.3 microns2), nuclear size (20.4 microns2), and granule diameter (0.81 micron) when compared with mast cells from adults with nonsystemic mastocytosis (36.3 micron 2, 15.4 microns2, and 0.67 micron, respectively) and normal age-matched control subjects (34.4 microns2, 14.1 microns2, and 0.67 micron, respectively). Lesional skin mast cells from infants with nonsytemic mastocytosis were very similar to adult nonsystemic mastocytosis mast cells but differed by several parameters from mast cells in adults with systemic involvement. This study demonstrates that there are quantitative differences between lesional skin mast cells from patients with systemic mastocytosis and those with nonsystemic disease. PMID- 3346415 TI - Basal cell carcinoma: response to systemic chemotherapy for lung carcinoma. AB - Two patients had regression of basal cell carcinoma while receiving systemic chemotherapy for carcinoma of the lung. The chemotherapeutic agents with some efficacy in basal cell carcinoma are reviewed. Based on our patients and data from the literature, cisplatin appears to be a drug of potential usefulness in some patients with this neoplasm. PMID- 3346416 TI - Human lymphocyte antigen in actinic prurigo. AB - Thirty-one patients with actinic prurigo were human lymphocyte antigen (HLA) typed. The results showed an association of this disease with the alleles B40 and Cw3, both usually found in linkage disequilibrium in most populations. Because these two antigens are more frequent in Amerindians than in whites, it is suggested that they may partly account for the restricted ethnic distribution of this disease. PMID- 3346417 TI - Multiple symmetric lipomatosis: treatment with liposuction. AB - Multiple symmetric lipomatosis is a fascinating disease of uncertain etiology that manifests as massive lipomatous deposits in specific areas of the body. The clinical syndrome and possible pathogenesis are discussed. Classic surgical lipectomy has been the only treatment thus far reported; we report a patient successfully treated with liposuction. PMID- 3346418 TI - Histopathologic study of Koenen tumors. Are they different from acquired digital fibrokeratoma? AB - Fifteen periungual fibromas from nine patients were studied histologically. The lesions were elongated. Capillaries were found in the distal part surrounded by thin collagen bundles whereas the proximal part was made up of dense, closely packed fibers. The epidermis covering the tumor appeared to be connected with the nail fold. The dense collagen of the lesion faded into the normal structure of the cutis of the proximal nail fold. Periungual fibromas can be subdivided into (1) fibrokeratomas originating from the dermal connective tissue and (2) fibrokeratomas originating from the proximal nail fold. PMID- 3346419 TI - Cutaneous endometriosis: a histopathologic study. AB - A detailed examination of material from 10 cases of cutaneous endometriosis revealed a range of histopathologic features similar to those found within the uterine endometrium at each of the main phases of the menstrual cycle. However, there appeared to be a poor correlation between histologic appearance and menstrual stage. Recognition of these cyclic variations is important for the accurate diagnosis of cutaneous endometriomas. PMID- 3346421 TI - Nystatin cream may contain ethylenediamine. PMID- 3346420 TI - Nonacquired immunodeficiency syndrome-related Kaposi's sarcoma after severe infection. PMID- 3346422 TI - Topical cyclosporine in psoriasis. PMID- 3346423 TI - Erythema multiforme due to clofibrate. PMID- 3346424 TI - Primary nodular endophytic basal cell carcinoma. PMID- 3346425 TI - Diagnostic value of cutaneous cytology in opportunistic fungal infections of patients with acquired immunodeficiency syndrome. PMID- 3346426 TI - Influence of pharmaceutical companies on medical research. PMID- 3346427 TI - Potent topical steroids and psoriasis. PMID- 3346428 TI - Generic equivalence of dermatologic products. PMID- 3346429 TI - Congenital triangular alopecia. PMID- 3346430 TI - Structural changes in hair with fungus infections. PMID- 3346431 TI - Prostatic carcinoma with metastasis to the nipple. PMID- 3346432 TI - Spindle cell hemangioendothelioma of the skin. PMID- 3346433 TI - Clinical presentation of scabies in a nursing home population. PMID- 3346434 TI - Classification and prediction of smoking relapse episodes: an exploration of individual differences. PMID- 3346435 TI - Use of the MMPI to identify malingering and exaggeration of psychiatric symptomatology in male prison inmates. PMID- 3346436 TI - Validity of physiological measures of pedophilic sexual arousal in a sexual offender population. PMID- 3346437 TI - Integrating clinical assessment with cognitive neuroscience: construct validation of the California Verbal Learning Test. PMID- 3346438 TI - Hopelessness, social desirability, depression, and parasuicide in two college student samples. PMID- 3346439 TI - Peer social status of children with anxiety disorders. PMID- 3346440 TI - Competition in a minimal-contact weight-loss program. PMID- 3346441 TI - Further studies of the Wonderlic Personnel Test as a brief measure of intelligence. PMID- 3346442 TI - Neurobehavioral and life-quality changes after cerebral revascularization. PMID- 3346443 TI - Readability of child and adolescent self-report measures. PMID- 3346444 TI - Anger, hostility, and depression in domestically violent versus generally assaultive men and nonviolent control subjects. PMID- 3346445 TI - Affective responses to conflictual discussions in violent and nonviolent couples. PMID- 3346446 TI - Effects of adult and peer social initiations on the social behavior of withdrawn, maltreated preschool children. PMID- 3346447 TI - Early intervention for parents at risk of child abuse and neglect: a preliminary investigation. PMID- 3346448 TI - Another look at the nonspecific hypothesis of therapeutic effectiveness. PMID- 3346449 TI - Long-term effects of incestuous child abuse in college women: social adjustment, social cognition, and family characteristics. PMID- 3346450 TI - Vanderbilt Psychotherapy Process Scale: a replication with adult outpatients. PMID- 3346451 TI - Cognitive training in alcoholic men. PMID- 3346452 TI - Marital interactions of alcoholic couples: comparison with depressed and nondistressed couples. PMID- 3346453 TI - Sensitizing effects of pretreatment measures on cancer chemotherapy nausea and vomiting. PMID- 3346454 TI - Mississippi Scale for Combat-Related Posttraumatic Stress Disorder: three studies in reliability and validity. PMID- 3346455 TI - Substantiation of child abuse and neglect reports. PMID- 3346456 TI - Adjustment of young adolescents in two-parent nuclear, stepfather, and mother custody families. PMID- 3346457 TI - Correlates of competence in a child psychiatric population. PMID- 3346458 TI - Hinged digit flap with dual W-plasties. PMID- 3346459 TI - Facial plastic surgery. PMID- 3346460 TI - Office surgery: the surgical suite. AB - A brief history of office based surgery as well as a guide to economic and practical considerations for new facility planning. PMID- 3346461 TI - Advantages of the paramedian scalp reduction. AB - The paramedian scalp reduction as compared to the midline (sagittal) scalp reduction provides distinct advantages, particularly in the patient who has undergone reconstruction of the frontal hairline. The paramedian approach causes less distortion of the frontal hairline, allows greater direct visualization of the advancement flaps, permits more extensive undermining, creates less stretchback, provides for coronal advancement of the hair-bearing occipital donor site, and allows for a greater amount of camouflage of the scalp reduction scar during the immediate postoperative period. Surgeons should be knowledgeable and capable of providing varied forms of scalp reduction procedures to meet the specific needs of the various patients that present for hair replacement surgery. PMID- 3346462 TI - Clinical photography utilizing office staff: methods to achieve consistency and reproducibility. AB - This report describes solutions to common problems incurred in clinical photography for facial and cosmetic surgery and focuses on the physician who utilizes office staff to obtain photographs. Issues addressed include space and room requirements, camera and lens, lighting and shadows, pose, retrieval, and quality control. The methods and systems described are aimed at assisting the physician in obtaining consistent, reproducible, quality pre- and postoperative photographs. PMID- 3346463 TI - Ablation of facial scars by programmed dermabrasion. AB - Revisions of scars, characteristically deferred for 6 to 12 months after wounds have healed, are performed to improve function and appearance. However, none of the techniques that has evolved to modify cicatrical deformities has afforded total, permanent effacement of scars already present. Evidence is presented here that dermabrasion of both surgical and accidental scars of the face, done 4 to 8 weeks after the primary wound, usually eliminates visible residual cicatrization. PMID- 3346464 TI - Facial liposuction and microlipoinjection. AB - Liposuction and microlipoinjection can be used to improve the contour of the face, correct certain defects, and improve signs of aging. The technique of facial liposuction as well as that of collecting and injecting the fat used for microlipoinjection (autologous fat transplantation), is described. PMID- 3346465 TI - Three-dimensional nursing: new partnerships between service and education. PMID- 3346466 TI - The Columbia precepting program: building a bridge with clinical faculty. PMID- 3346467 TI - Faculty practice: a new perspective on academic competence. PMID- 3346468 TI - A federal focus for nursing. PMID- 3346469 TI - Blending qualitative and quantitative approaches to instrument development and data collection. PMID- 3346470 TI - What does nursing education cost? Turning the question around. PMID- 3346472 TI - Identification of predictors of success for the NCLEX and students at risk for NCLEX failure in a baccalaureate nursing program. PMID- 3346471 TI - Scholarly productivity: a survey of nursing faculty researchers. PMID- 3346473 TI - Victims of torture. PMID- 3346474 TI - Home treatment of mild, acute diarrhea and secondary dehydration of infants and small children: an educational program for parents in a shelter for the homeless. PMID- 3346475 TI - Toward living wills. PMID- 3346476 TI - College, the quality of life. PMID- 3346477 TI - Impact of the future on college health. PMID- 3346478 TI - Bunk bed injuries in college students. PMID- 3346479 TI - Health behavior change and the college personal health class: a multifaceted approach. PMID- 3346480 TI - Premature return to school following a psychotic episode. PMID- 3346481 TI - The course of asthma during pregnancy, post partum, and with successive pregnancies: a prospective analysis. AB - We studied 366 pregnancies in 330 prospectively managed women with asthma to determine the effect of pregnancy on asthma. Asthma activity was assessed by (1) daily symptom and medication diaries and (2) monthly auscultation and spirometry during pregnancy and for 3 months post partum. At 3 months post partum, subjects were asked to assess the overall course of their asthma during pregnancy compared to the usual course for them, and the course of their asthma during the 3 months post partum compared to the asthma during pregnancy. Asthma worsened during pregnancy in 35% of the women, improved in 28%, and was unchanged in 33%. Based on diary-card analysis, asthma was significantly less frequent and less severe during the last 4 weeks of pregnancy than during any other gestational interval. In women whose asthma improved during pregnancy, diary-card analysis revealed a gradual improvement with progressive pregnancy, whereas in women whose asthma worsened during pregnancy, there was an increase in asthma symptoms during 29 to 36 weeks gestation. During labor and delivery, asthma symptoms occurred in 10% of women with approximately equal proportions of these women receiving either no treatment or inhaled bronchodilators; only two subjects required intravenous aminophylline. During the 3 months post partum, asthma reverted toward its prepregnancy course in 73% of women. In 34 subjects prospectively studied for two successive pregnancies, there existed a significant concordance between the asthma course during the first and second pregnancies. The mechanistic and clinical implications of these findings are discussed. PMID- 3346483 TI - Methylxanthines inhibit exercise-induced bronchoconstriction at low serum theophylline concentration and in a dose-dependent fashion. AB - We studied the relationship between attenuation of exercise-induced bronchoconstriction and serum theophylline concentration in a dose-dependent fashion in 11 patients with mild bronchial asthma. In addition, we investigated the protection of equal amounts of theophylline either dissolved in ethylenediamine or in proxyphylline and diprophylline. At 4 separate study days, the patients received one of the following preparations in a double-blind random order: saline solution, 200 mg of theophylline in 19.9 mg of ethylenediamine (TE200), 351 mg of theophylline in 35 mg of ethylenediamine (TE351), and 200 mg of theophylline in 300 mg of propxyphylline and 300 mg of diprophylline (TPD). Fifteen minutes after the end of infusion, a standardized exercise test during cold air breathing was performed. Before and up to 30 minutes after each test, specific airway resistance and FEV, were determined. Postexertional bronchoconstriction after theophylline was expressed by means of a protection index, a value of 0 or 1 meaning no or full protection, respectively. At mean (SD) serum theophylline concentrations of 6.7 (1.3), 10.1 (1.7), and 6.3 (1.4) mg/L, respectively, TE200, TE351, and TPD for specific airway resistance caused a significant bronchodilation (p less than 0.05) and resulted in mean (SD) protection indices of 0.61 (0.15), 0.82 (0.14), and 0.65 (0.20), respectively, being significantly different from 0 (p less than 0.01). The protective effect of TE200 and TPD was equal and significantly less pronounced as compared to TE351 (p less than 0.01). Therefore, theophylline attenuated exercise-induced bronchoconstriction in a dose-dependent fashion with significant protection at serum concentrations of about 6 mg/L. The effect of intravenous theophylline was independent of the diluents. PMID- 3346482 TI - Occupational allergy to locusts: an investigation of the sources of the allergen. AB - Allergic symptoms occur commonly in subjects working closely with locusts and are associated with specific IgE antibody. Extracts of intact locusts (Schistocerca gregaria and Locusta migratoria) were used to identify specific IgE antibody, to define the major allergens of the locust and their sources, and to estimate aeroallergen concentration in the working environment. With questionnaire, skin prick tests, and specific IgE measurements, 35 individuals, working in a research center, were surveyed. Of the 15 currently exposed individuals, contact with locusts provoked asthma, rhinitis, and contact urticaria in five, rhinitis and urticaria in three, and rhinitis alone in one individual. Symptoms provoked by locusts and skin test reactions to locust extracts were associated with specific IgE antibody in the serum. The "immunoblot" technique demonstrated the presence of multiple allergens in the locust extracts of approximately 68, 66, 54, 43, 37, 29, and 18 K daltons molecular weight. Locust antigen was identified in the atmosphere by means of an immunochemical method involving elution of high-volume air-sampler filters exposed in the locust breeding room and analysis of eluate allergen content by RAST-inhibition assays. Logit transformation of RAST inhibition lines demonstrated that the filter extract shared a common slope with the locust extract and with an extract of locust gut. This gut extract also shared a common slope with extracts of locust feces and peritrophic membrane. The major source of allergen appears to be the peritrophic membrane that is present in the gut and is excreted surrounding the feces. PMID- 3346484 TI - False positive and false negative reactions encountered in the use of sulfite test strips for the detection of sulfite-treated foods. AB - The reliability of a qualitative test for sulfites in foods (Sulfitest sulfite test strips) was evaluated by comparison of the results obtained from the analysis of 90 food and beverage samples to results obtained by the quantitative, modified Monier-Williams method (the preferred procedure for sulfite analysis in foods of the Food and Drug Administration). The results obtained with the sulfite test strips compared favorably to the results of the Monier-Williams procedure when the sulfite test strips were used on sulfite-treated lettuce and raw or cooked potatoes. However, the strips yielded many false negative and false positive results with other types of foods. False positive results (strips indicated a substantial amount of sulfite when sulfite was not detectable by the Monier-Williams method) were obtained with fin fish, red meats, and poultry. False negative results (strips indicated the absence of sulfites when sulfite was detected at levels greater than 10 ppm total sulfur dioxide by the Monier Williams method) were obtained with dried fruits and wines under certain conditions of testing. The false negative responses with the test strips may result in the hazardous consumption of foods with high levels of sulfites, such as dried fruit or wine, by a sulfite-sensitive individual. The false positive responses would not be hazardous but could lead sensitive individuals to avoid foods that could be safely consumed. Although the strips may be useful for the detection of sulfites in certain foods, such as lettuce and potatoes, their use by sulfite-sensitive individuals cannot be recommended because of the confusion and potential hazards posed by the false negative and false positive responses. PMID- 3346486 TI - Phenol amplifies complement-fixing activity and induces IgG-precipitating activity in grain-dust extract. AB - The use of phenol as a preservative in extracts of grain dust was found to be associated with an amplification of complement-fixing activity and the appearance of IgG-precipitating activity. Both activities were absorbed by IgG, suggesting that they were due to a single material. Phenol itself neither fixed complement nor formed a precipitate with IgG. 14C-labeled phenol was incorporated into the IgG precipitating material. Both the amplification of complement-fixing activity and the appearance of IgG-precipitating activity in phenol-containing grain-dust extract were dependent on the presence of air and were inhibited by heating the extract before phenol addition. One interpretation of these results is that a component of grain-dust extract, possibly an enzyme, oxidatively modifies phenol to a form that fixes complement and precipitates IgG. The modified material demonstrates properties of a polyphenol (tannin). PMID- 3346485 TI - Nasal mucosal blood flow after intranasal allergen challenge. AB - The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the 133Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen induced changes in blood flow were reflex mediated. PMID- 3346487 TI - Antigenic/allergenic characterization of American and German cockroach extracts. AB - Cockroach allergens have been implicated as clinically significant sensitizing agents in the induction/exacerbation of "urban asthma." In the present study, approximately 50% of atopic, predominantly inner-city residents had immediate wheal-and-flare cutaneous reactivity to a commercial American cockroach whole body extract. Crude whole body extracts were prepared in our laboratory from both American (Periplaneta americana) and German (Blatella germanica) cockroach species. Crossed immunoelectrophoresis of American cockroach whole body extract (AWBE) and German cockroach whole body extract (GWBE) detected a total of 50 and 56 precipitin peaks, respectively, when extracts were reacted with hyperimmunized rabbit antisera. Crossed radioimmunoelectrophoresis identified at least five electrophoretically distinct allergens each in AWBE and GWBE. Cockroach whole body extracts produced two major protein peaks when extracts were fractionated on Sephadex G-75. RAST-inhibition studies demonstrated allergens in both peak 1 and the immediate trailing fractions of the column. Direct RAST and end point prick skin testing confirmed the presence of significant/important allergens in column "fraction 2" of AWBE. Skin testing and RAST analysis suggested the occurrence of shared and species-specific allergens between AWBE and GWBE. Collectively, these studies confirm the important sensitizing potential of cockroach allergens, characterize their number and size distribution by crossed radioimmunoelectrophoresis and column chromatography, support the occurrence of significant allergens in column "fraction 2," and suggest the occurrence of both species-specific and shared interspecies allergens. PMID- 3346488 TI - Allergy in long-term hemodialysis. II. Allergic and atopic patterns of a population of patients undergoing long-term hemodialysis. AB - Maintenance hemodialysis is widely used throughout the world, and anaphylactic reactions appear to be increasing in number and severity. However, the exact incidence of sensitization and the role of atopy in these reactions are not yet fully understood. All of the 111 patients routinely dialyzed in a center were tested. All patients had a complete investigation of atopy, RAST to chemicals released during the procedure of dialysis (ethylene oxide (Eto), formaldehyde, phthalic anhydride, and toluene diisocyanate), skin tests with the effluent, and the titration of blood eosinophils. The incidence of atopy was found to be lower (13.5%) than in the normal population of the area. Skin tests with either histamine or allergens are significantly (p less than 0.001) smaller than those of nondialyzed subjects, and this method does not appear to be ideal in this population of patients. Eto sensitivity ranked first (5.5%), followed by phthalic anhydride sensitivity (3.6%); 5/6 patients who had a sensitivity to Eto and/or phthalic anhydride presented symptoms during dialysis, but they never were life threatening. Formaldehyde RAST was only found in one patient who had a life threatening reaction. Finally, three patients presenting pruritus had positive skin prick tests with the effluent of the dialyzer. All patients having a first use syndrome and 80/81 symptom-free patients did not have serum-specific IgE against the released chemicals, 5/17 patients who had a pruritus during dialysis had either positive RAST to released chemicals or skin tests to the effluent, 5/8 patients who suffered from anaphylaxis had positive RAST to released chemicals, but only those who had a positive RAST presented a severe reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346489 TI - An on-line computer data bank of monoclonal antibodies that recognize allergens- invitation for entries. AB - Monoclonal antibodies that recognize allergens are potentially extremely useful reagents for use in a variety of applications, including highly specific and sensitive assays for the standardization of allergen extracts and the measurement of environmental allergens, epitope mapping of allergens, comparison of IgE binding determinants, and the immunolocalization of allergens in thin sections. Although monoclonal antibodies have many properties that enable them to be shared internationally, it is difficult to know from the literature what monoclonal antibodies are available and, in some cases, what are the individual characteristics of the antibodies. We are organizing an on-line data base of information about allergen-reactive monoclonal antibodies, which can be accessed by computer with international telecommunications networks. Each record of a monoclonal antibody includes details, if they are known, of allergen source and name, antibody production, complimentary antigenic determinant, names and addresses of the owners, availability of the antibody, and other important information. Investigators who have produced monoclonal antibodies that react with allergens are invited to submit details of the antibodies for inclusion in the data base. PMID- 3346490 TI - Xanthines as airway anti-inflammatory drugs. PMID- 3346491 TI - Computer-analyzed dietary intake printouts: guidelines for their design and student comprehension. AB - The purpose of this study was to determine the ability of individuals to comprehend and interpret information on nutrient analysis computer program printouts and to assess their understanding of certain concepts closely related to such printouts, specifically the Recommended Dietary Allowances (RDAs) and vitamin and mineral supplementation. The study sample comprised 553 college students who were randomly assigned to one of seven groups. Each group received a nutrient analysis computer printout that varied in terms of type, amount, and format of information supplied. Printouts with varying characteristics were used in order to identify those elements that contributed to the greatest and most correct understanding and interpretation. A 30-item objective knowledge test was used to assess understanding and ability to interpret information on the printouts. Research results indicate that most individuals had misconceptions concerning the RDAs and vitamin and mineral supplementation. Recommendations were made for improving the information provided on printouts regarding these two topics. Subjects had little difficulty in reading the printout correctly. However, groups whose printouts included only nutrient data generally had more difficulty using the information to draw appropriate conclusions and identify ways to improve dietary intake than did individuals whose printouts included short messages listing sources and functions of nutrients. Data presented in graphic format were more easily understood than data in spreadsheet form. Eight design recommendations intended to assist nutritionists and software designers in selecting and/or creating printouts were made on the basis of the results of this study. PMID- 3346492 TI - Interdisciplinary case management: a model for intervention. AB - Interdisciplinary case management is required when clients present problems that do not fall within the purview of any one discipline. The interdisciplinary approach entails the participation of professional and support staff, along with the client and his/her family, in diagnosis, individual program planning, implementation, and evaluation. For example, interdisciplinary case management for a patient with Prader-Willi syndrome (PWS) results in cost-effective, efficacious treatment. Because of the diversity of symptoms, the treatment of Prader-Willi syndrome must incorporate knowledge and skills from a variety of areas. A model for the interdisciplinary case management of PWS is presented. The model is problem focused and emphasizes goals formulated and acted upon by the disciplines represented on the client's treatment team. Communication and coordination of efforts are central to the utility of the model. Additional benefits of interdisciplinary case management include the opportunity for ongoing education and role expansion of team members. PMID- 3346494 TI - Research activities and research skill needs of nutrition support dietitians. PMID- 3346493 TI - FDA's Factored Food Vocabulary for food product description. AB - The Food and Drug Administration's Factored Food Vocabulary (FFV) uses standardized language to describe characteristics of food products that are important for food safety and nutritional quality. Each food product is described by a set of descriptors from the following factors: product type; food source; part of plant or animal; physical state, shape, or form; degree of preparation; cooking method; treatment applied; preservation method; packing medium; container or wrapping; food contact surface; and user group. The purpose of the vocabulary is to facilitate retrieval of food composition, food consumption, food contamination, and other food-related data relative to these factors. The major advantages of this system are flexibility with specificity, enhanced searchability with economy, and ease of change and updating. PMID- 3346496 TI - Treatment for significant others of bulimic patients may be beneficial. AB - This study indicates that modeling an assistance program for the concerned others of bulimic patients after programs for the concerned others of alcoholic patients may produce benefits. The program was constructed on the basis of findings in the literature regarding alcoholics. Research is needed to evaluate its effects. PMID- 3346495 TI - What characterizes elderly women who overuse vitamin and mineral supplements? AB - This study has identified some potentially important characteristics of elderly women who overuse vitamin and mineral supplements. These women tended to live alone and to have medical problems. The supplements were usually self-prescribed and purchased in a drugstore. The sources of information that supported supplement use were primarily the print media and family and friends rather than health professionals. Other studies have made similar findings. The degree of IHLC orientation failed to predict the amount of supplement use, although IHLC was shown to be useful in a recent study that included both young and elderly women. Thus, from our perspective, the identification of possible overusers of supplements should begin with elderly women who have health problems and live alone; point-of-purchase information should be targeted to drugstores. In this study and in other, either the actual reasons for supplement use were often inappropriate or the diets were adequate in many of the vitamins taken by supplements, such as vitamins A and C. Thus, education for elderly women that stresses the appropriate reasons for nutrient supplement use is clearly needed so that a correct link between nutrition need and use always is maintained. The high IHLC scores suggest that the majority of women in this study want to make their own decisions about their health. Given better information, overusers of supplements might instead choose a more reasonable approach for improving their diets. Dietitians/nutritionists were not usually used as a source of nutrition information by the elderly women in this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346497 TI - Position of the American Dietetic Association: vegetarian diets. PMID- 3346499 TI - Plans for update of the role delineation studies. PMID- 3346498 TI - Position of the American Dietetic Association: vegetarian diets--technical support paper. PMID- 3346500 TI - Continuing education needs of personnel in public health nutrition in the eight southeastern states. PMID- 3346501 TI - Vitamin A and teratogenesis: recommendations for pregnancy. PMID- 3346503 TI - Clarification of infant formula's iron content. PMID- 3346502 TI - No sucrose in ProSobee in the U.S. PMID- 3346504 TI - Caffeine and health risk. PMID- 3346505 TI - Recommendations in achieving a prompt diagnosis of osteomyelitis. PMID- 3346506 TI - Usage of radiopaque contrast media in the foot and ankle. AB - The author presents a wide variety of uses of radiopaque contrast media in the foot and ankle. Dye studies can aid the physician in diagnosing pathology of the soft tissues and joints without surgical intervention. The results of these tests aid in determining the course of treatment. PMID- 3346507 TI - Diagnosis and treatment of the ruptured Achilles tendon. AB - The authors review the basic principles of tendon healing and repair as they apply to a ruptured Achilles tendon, and discuss its diagnosis and treatment. The treatment, either surgical or conservative, is a controversial subject. Both forms have their problems. The authors conclude that while surgical repair is the treatment of choice in most cases, conservative management should be considered an effective alternative. PMID- 3346508 TI - Nutrition in podiatric surgery. AB - Although obtaining the preoperative nutritional status of the typical elective podiatric surgical patient is not usually addressed, knowledge of malnutrition towards surgical success and basic parameters to identify malnutrition is imperative. This paper will attempt to provide information to better prepare the patient for essential postoperative healing and minimize possible complications. PMID- 3346509 TI - Fractured anterior calcaneal process. AB - The case report of an intra-articular calcaneal fracture is presented. The case is noteworthy because the entire anterior process was fractured and dislocated into the subtalar joint. Treatment consisted of open reduction and internal fixation with good results. The literature was reviewed and an aggressive treatment posture adopted in order to prevent the long-term disability often associated with this type of injury. PMID- 3346510 TI - Intraoperative bacteremia during foot surgery. AB - Numerous studies have shown that bacteremias occur in patients during and immediately after some types of surgeries, placing the patient at risk of serious infection. This study was designed to ascertain whether a bacteremia will exist following routine podiatric surgery. Blood cultures were taken perioperatively from 42 subjects, and were incubated both aerobically and anaerobically, and swabs of the incision were made during the surgery. No bacteremias occurred during this study. This suggests that podiatric surgery, when properly performed, does not present a risk of bacteremia to the patient. PMID- 3346511 TI - A retrospective analysis of modification of the flexor tendon transfer for correction of hammer toe. AB - A modified flexor tendon transfer for flexible and semiflexible toes has been described in this retrospective analysis. The study revealed three laterally deviated and one slightly dorsiflexed digit postoperatively. However, there were no recurrences of lesions or digital contractures. Varying degrees of joint stiffness was prevalent in each of the patients. The procedure was initially developed for contracted toes associated with pronated and rectus foot types. The author has found the procedure effective in cavus foot structures when other procedures failed to reduce the hammer toe deformities. The patient population studied found this procedure to be very gratifying. PMID- 3346512 TI - Steroid injection of a unicameral bone cyst of the calcaneus: literature review and two case reports. AB - Two interesting cases are presented, describing the diagnosis and treatment of unicameral bone cysts of the calcaneus. The first case report presents a patient who had a 5-month history of a painful right heel. The pain had been getting progressively worse and was aggravated by prolonged walking and physical activity. The second case report presents a patient whose unicameral bone cyst was discovered as a relatively incidental finding on radiographs; however, the patient later admitted that he had mild tenderness upon the plantar-lateral aspect of his right calcaneus with weightbearing. The authors reviewed the literature concerning the etiology and treatment of unicameral bone cysts. Attention is directed to the use of injectable steroid as an alternative means to open surgical intervention. Certain potential problems exist, in spite of the various surgical approaches utilized, including infection, postoperative fracture, recurrence, immobilization, and prolonged hospitalization. PMID- 3346513 TI - Prophylactic antibiotic usage in podiatric implant surgery of the first metatarsophalangeal joint. AB - All first metatarsophalangeal joint implants used at Sheridan Park Hospital from 1979 through 1984 were evaluated for postoperative infection and subsequent implant removal. Thirteen (1.3%) of 929 implants used were removed due to infection. Antibiotic prophylaxis was not determined to be necessary to avoid this complication. However, in all cases in which prophylaxis was used, no infection occurred. PMID- 3346514 TI - Ganglia (synovial cysts) of bone. AB - The authors present a case of an intraosseous ganglion of the third cuneiform bone. The clinical and histologic presentation is described, as well as surgical considerations in treatment. PMID- 3346515 TI - Subchondral bone cysts, osteochondritis dissecans, and Legg-Calve-Perthes disease: a correlation and proposal of their possible common etiology and pathogenesis. AB - Various theoretical hypotheses have been proposed for the nontraumatic etiology of osteochondritis dissecans, subchondral bone cyst formation, and Legg-Calve Perthes disease. Although a direct relationship between these distinct clinical entities has sparse referral in the literature, their common theories of etiology and evolution have been extensively documented, although not correlated. The various etiologic theories of osteochondritis dissecans, Legg-Calve-Perthes disease, and subchondral bone cyst formation have been individually presented. The conclusion drawn upon review of these theories would prove that all of the proposed etiologies for the above syndromes are remarkably similar. Furthermore, as referred to in the contents of this paper, the signs, symptoms, and roentgenographic findings also appear to be common to all three syndromes. Various clinicopathologic studies have demonstrated similar gross pathologic and histologic findings between osteochondritis dissecans, subchondral bone cysts formation, and Legg-Calve-Perthes disease. The authors, therefore, contend that the most likely nontraumatic etiology of this condition is a common multifactorial causation with an identical pathogenesis. They propose a common etiology resulting in a pathologic process, originating in subchondral cyst formation. Eventually, a communication between the cysts and the joint will occur secondary to either the duration and progression of the cystic process, endogenous, or exogenous stress resulting in collapse of the articular surface. A complete or partially detached osteochondral fragment results from these forces. Osteochondritis dissecans and Legg-Calve-Perthes disease may represent the same stage in the pathologic process. Degenerative joint disease is the final stage of this pathologic process. Further studies need to be performed to explore this relationship and the proposed pathogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346516 TI - Osteoblastoma of the foot. PMID- 3346517 TI - Influences of aging and dietary restriction on serum thymosin alpha 1 levels in mice. AB - Influences of age (3 wk, 2, 7, 19, or 26 mo), long-term dietary restriction (DR) started at 3 wk of age, and acute fasting state on serum thymosin alpha 1 (T alpha 1) levels were measured by radioimmunoassay in female mice from a long lived strain. The average T alpha 1 level was highest (approximately 60 ng/ml) at 3 wk and fell sharply such that 2 mo old mice fed either normal (N, approximately 80% of ad libitum intake) or restricted (R, approximately 50% of ad libitum intake) diets averaged approximately 20 ng/ml. Any age-related declines after 2 mo of age were mild and statistically significant only for R mice bled 2-4 h (but not 24-48 h) post-feeding. T alpha 1 levels were lower in group R than in group N mice in one experiment at 19 mo of age but not in another at 26 mo. The decline with age in serum T alpha 1 levels is mainly a very early life event for mice of this hybrid strain and appears uninfluenced by DR. T alpha 1 levels are variably reduced by DR later in life. PMID- 3346518 TI - A set of test life tables for theoretical gerontology. AB - Prediction of life tables, which provide the most empirical information available about the statistical properties of aging, provides a rigorous test for any theory of aging as manifested at the organismic level of biological organization. For this purpose, a set of test tables for the wild boar (Sus scrofa), domestic sheep (Ovis aries), Dall sheep (Ovis dalli dalli), African buffalo (Syncerus cafer), and hippopotamus (Hippopotamus amphibius) is reconstructed from primary data taken from the literature. The tables, which exhibit a broad range of survival characteristics, satisfy the criteria that (1) the data are statistically sound, (2) their survival functions are concave, except for the limiting case of the convex wild boar function, and (3) the species are natural populations (i.e., are in the same environment in which they evolved). Each test table is reported numerically and as a least-squares regression formula for the age-specific mortality rate over a given range of age. PMID- 3346519 TI - Enhancement by food restriction of liver protein synthesis in the aging Fischer 344 rat. AB - Age-related changes in liver protein synthesis of ad libitum fed and food restricted SPF Fischer 344 rats have been measured. In ad libitum fed animals, valine incorporation increased from 3 to 6 mo of age, decreased to the 3-mo level at 12 mo, remained relatively constant through 18 mo, and then declined further at 24 mo of age. By 24 mo valine incorporation was 30% of the 6-mo value. Food restriction had no effect at 3 mo of age (6 wk of restriction) but at 6 mo the rate of valine incorporation was 35% greater than the control, an increment that was maintained throughout the life of the animal. Therefore, although food restriction does not prevent the age-related decline in protein synthesis, it does maintain the rate of liver valine incorporation at levels greater than those observed in the liver of the ad libitum fed animal. PMID- 3346521 TI - Quality of life in chronic diseases: perceptions of elderly patients. AB - Quality of life is an important consideration in medical decisions involving elderly patients and a clinical outcome measure of health care. Elderly outpatients (N = 126) with five common chronic diseases (arthritis, ischemic heart disease, chronic pulmonary disease, diabetes mellitus, and cancer) and their physicians were interviewed to better characterize patient quality of life. Patients generally perceived their quality of life to be slightly worse than "good, no major complaints" in each chronic disease. Physicians' ratings were generally worse than and only weakly associated with the patients' ratings of quality of life in each chronic disease. Significant independent correlates of patients' ratings of quality of life included the patients' perceptions of their health, interpersonal relationships, and finances. These results suggest that quality of life in elderly outpatients with chronic disease is a multidimensional construct involving health, as well as social and other factors. Physicians may misunderstand patients' perceptions of their quality of life. PMID- 3346520 TI - Effect of acute arecoline, tacrine, and arecoline + tacrine post-training administration on retention in late middle-aged mice. AB - The amnesias characteristic of Alzheimer's disease and other age-related dementias are refractory to conventional pharmacotherapy. A recent treatment strategy is to combine drugs, particularly cholinergic drugs, to improve their memory enhancing effect. We previously reported that in young, weakly trained mice, the combination of arecoline and tacrine was more effective on a mg/kg basis than either drug administered alone. This was true whether the route of administration was intracerebroventricular, subcutaneous, or oral. These drug treatments have also been found to improve retention in 24-month-old mice. Mice 24 months of age show very poor recall one week after training. Failing memory must develop over time but may only be detected in mice younger than 24 months of age when the retention test interval is substantially longer. We now report that 18-month-old mice trained to avoid footshock in a T-maze show poor retention when tested two months after training and drug administration. Subcutaneous administration of arecoline, tacrine, and arecoline plus tacrine all enhanced retention of 18-month-old mice compared to the saline-injected control. The combination was as effective as the single drug treatments even though 96% less arecoline and 99.7% less tacrine were administered. PMID- 3346523 TI - Measurement and correlates of verbosity in elderly people. AB - Two studies were conducted to develop measures of verbosity in elderly people and to determine the social and psychological correlates of verbose speech. In the first study, 346 elderly people were classified into three categories of verbosity on the basis of their verbal behavior during an interview and questionnaire session. Personality variables, stress in daily living, and age differentiated extremely verbose individuals from others. In the second study, frequency and extent of off-target speech were rated quantitatively for the verbal behavior of 203 older men, with a second rater independently making the same ratings for 98 of the men. Classification into the three categories of verbosity was made for 179 of the men. Interrater reliability was established at .76 and .70 for the two measures of verbosity. There was significant agreement between the qualitative classification and the quantitative rating assessments of verbosity. In addition to the previously found associations between verbosity and personality and social variables, higher nonverbal intellectual performance scores obtained in the early adult years combined with poorer current nonverbal scores predicted verbosity in late life. PMID- 3346522 TI - Lack of correlation between indices of nutritional status and immunologic function in elderly humans. AB - We studied 230 independently living healthy elderly men and women to examine the hypothesis that subclinical nutritional deficiencies contributed to depressed immune function seen in the elderly. Immunologic function was assessed with delayed type hypersensitivity skin testing to four antigens, in vitro lymphocyte culture with phytohemagglutinin, lymphocyte count, and presence of serum autoantibodies and circulating immune complexes. Nutritional status was assessed by 3-day diet records and also biochemical analyses of blood for vitamins A, B12, C, D, E, riboflavin, folic acid, and the minerals iron, copper, and zinc. Using a variety of analyses we found no association between malnutrition and depressed immunologic function in this population. We conclude that subtle nutritional deficiency is not a noticeable contributor to the immunodeficiency of aging, and that previously reported beneficial effects of "megadose" nutritional supplements on the immune response of elderly individuals probably represent a pharmacologic effect rather than the correction of nutritional deficiencies. PMID- 3346524 TI - Reminiscence and autobiographical memory in the study of the personal past. AB - This study investigated adult age differences in memory for past personal experiences. Young, middle-aged, and older adults participated in an autobiographical memory task in which they were presented with word prompts and asked to report the first specific personal memory that came to mind. They also completed a reminiscence questionnaire and a measure of current well-being, the Bradburn Affect Balance Scale (ABS). The autobiographical memory data revealed significant increases across the three age groups in both the average time taken to respond to prompt words and the average "age" of reported memories. Age differences in reminiscence also were found. The hypothesis that persons who actively reminisce would respond more quickly and with more remote memories in the autobiographical memory task was not supported. Implications of this data for understanding the cognitive and functional aspects of personal memory are discussed. PMID- 3346525 TI - A longitudinal study of depressed mood and sleep disturbances in elderly adults. AB - Previous studies have suggested that depression might be more strongly related to sleep disturbances in older than in younger individuals. However, few of these studies have simultaneously considered variables other than depression that have been demonstrated to influence the sleep of elderly persons, and none has examined the relationship between depression and sleep longitudinally. The present study examined the association between frequency of depressed mood, using the Depression Adjective Checklist (DACL), and self-reports of four sleep problems over a 3-year period in a sample of community-residing elderly persons. Results showed that frequency of depressed affect was related positively to sleep disturbance, even when subjects' age, gender, and health status were considered simultaneously. Early morning awakening was the sleep symptom that most consistently related to depressed mood over the course of the study. Poor health and female gender showed positive but less consistent relationships to the sleep complaints than depressed affect. Research on biological mechanisms underlying the disturbed sleep of elderly depressed individuals is discussed. PMID- 3346526 TI - The relationships of coping responses to physical health status and life satisfaction among older women. AB - This study examined a model specifying the causal links between the physical, functional, and subjective components of physical health status and life satisfaction among older women, and assessed the effects of three coping responses (direct-action, positive-cognitive, and passive-cognitive coping) at each point in the process. Based on interview data with 281 older women, a series of regression analyses indicated that, before the inclusion of the coping variables, physical conditions directly contributed to functional impairment, and both indirectly lowered life satisfaction through their direct negative effects on subjective health assessments. Further analyses indicated that positive cognitive coping buffered the effects of physical conditions at each point in the model, that passive-cognitive coping generally had deleterious effects on health status, although it prevented negative health assessments from lowering life satisfaction, and that direct-action coping had little effect. These findings emphasize the importance of a multidimensional conceptualization of physical health status in understanding its relationship with life satisfaction as well as the specific functions of coping at different points in the process for older women. PMID- 3346527 TI - Confidants and family structure in old age. AB - Previous research has shown that confiding has a major influence on well-being in old age, but little is known about the availability and selection of confidants. Drawing from a survey of the social networks of 1,050 persons aged 60 and older in Sydney, Australia, this study explored aspects of the influence of age, gender, and family structure in predicting the choice of confidants among potentially available spouses, children, siblings, and other persons in informal relationships. Logistic regression was used because the response variable was dichotomous and because several explanatory variables, which were both categorical and continuous, were being examined simultaneously. The findings indicated that people tended to confide in more distant family or nonfamily when close family members were not available. The relative importance of variables differed substantially between types of confiding relationships and between gender and age groups of respondents. Our findings suggest the need for longitudinal research and more sensitive methods of analysis in exploring the complexities of maintaining and re-forming primary bonds through the course of old age. PMID- 3346528 TI - Incidence, timing, and events associated with poverty: a dynamic view of poverty in retirement. AB - Using longitudinal data from the Retirement History Study (RHS), we traced the economic well-being of couples who were not poor just prior to retirement through up to 10 years of retirement. The vast majority of these couples did not become poor during their first years of retirement. However, the risk and pattern of poverty during retirement varied greatly across groups identified by marital status and pension status. Married couples with pension income who survived over the period of our analysis rarely fell into poverty. Even surviving couples without pension income were not very likely to face poverty. Our findings indicate, however, that the death of a husband dramatically alters the risk and pattern of poverty in retirement. PMID- 3346529 TI - Stressful life events and physician utilization. AB - The primary purpose of this study was to determine if the literature on stress and coping could be useful for studying patterns of physician utilization among older adults. It was hypothesized that elderly people with strong social support systems would be less likely to visit a physician in times of high stress than would older adults who receive less social support. This hypothesis was partially confirmed by the data. The second goal of this study was to determine whether or not locus of control beliefs buffer the effects of stress on physician use. The data suggest that elderly persons with internal locus of control beliefs make fewer visits to the doctor's office in times of high stress than do those individuals with an external locus of control orientation. It should be noted that this study did not assess changes in physician use through time and that information on stress was gathered 18 months prior to the gathering of information on physician utilization. PMID- 3346530 TI - Treatment of acute hepatic porphyria with hematin. AB - The efficacy of hematin has been evaluated in eight patients with acute intermittent porphyria: six with acute attacks and two with chronic subacute symptoms. Hematin suppressed the chemical signs of porphyria in all patients and the symptoms in those with acute attacks. The clinical response to hematin occurred uniformly on the third or fourth day of treatment, suggesting that a stereotypic response to this form of therapy can be defined. Hematin had no effect on chronic subacute symptoms. The indications for hematin therapy, its rationale and the details of its administration are reviewed. PMID- 3346531 TI - Amodiaquine-induced fulminant hepatitis. AB - Three patients suffered from fulminant hepatitis within 23, 59 and 22 weeks after having ingested a total dose of 16, 26 and 15 g, respectively, of amodiaquine for the prophylaxis of malaria. Amodiaquine administration was continued for 44, 21 and 25 days after the onset of jaundice, respectively. One patient underwent emergency orthotopic liver transplantation and survived. The other two died. Fulminant hepatitis threatens patients in whom amodiaquine administration is protracted for several months and not interrupted when jaundice occurs. PMID- 3346532 TI - Analysis of factors predicting early seroconversion to anti-HBe in HBeAg-positive chronic hepatitis B. AB - To investigate whether data obtained at the time of diagnosis may serve to predict early seroconversion to anti-HBe in chronic hepatitis B virus infection, we have compared the clinical, pathological and virological features of two groups of patients with untreated HBeAg-positive chronic hepatitis B who showed a markedly different outcome. One group (early seroconverters) included 20 patients who developed a typical seroconversion to anti-HBe within the first year of prospective follow-up. The other group (non-seroconverters) was formed by 21 patients who remained seropositive for HBeAg and still had raised aminotransferase serum levels after at least 2 years of follow-up. The serum aminotransferases, the degree of periportal and lobular lesions, the amount of liver fibrosis and the total score index of histological activity were significantly higher but the amount of HBcAg in liver was smaller in early seroconverters. Stepwise logistic regression analysis demonstrated that the alanine aminotransferase serum levels, the Knodell's index of histological activity and the amount of HBcAg in liver had significant value as independent predictors of early seroconversion. Calculation of the probability of seroconversion for individual cases showed marked differences between the two groups of patients, suggesting that early seroconversion to anti-HBe may be predicted in some patients with chronic hepatitis B. PMID- 3346533 TI - Cell population kinetics of Kupffer cells during the onset of fibrosis in rat liver by chronic carbon tetrachloride administration. AB - The cell population kinetics of Kupffer cells (KCs) were investigated during the induction of fibrosis in rat liver by carbon tetrachloride. KCs, characterized microscopically by their specific peroxidase pattern, increased in number during the first 24 h after CCl4 injection. After repeated injections of the toxin the number of KCs increased logarithmically. After 9 weeks of CCl4 treatment, the KC population reached a new steady state with a 2.6-times-higher cell number than in control animals. Local KC proliferation was demonstrated by the metaphase arrest technique using vinblastine. It was calculated that at 24 h and at 72 h after one injection of CCl4, local proliferation did not account for the entire growth of the population. This means that, in addition to local proliferation of KCs, an influx of mononuclear phagocytes into the liver sinusoids occurred. PMID- 3346534 TI - Calcium carbonate in cholesterol gallstones. AB - CaCO3 has been studied in twelve gallstones in which cholesterol predominated. Different polymorphs of CaCO3, as well as carbonate-apatite, were characterised by X-ray diffraction, polarised light microscopy and scanning electron microscopy. Crystals and rhombohedral aggregates of calcite, aggregates of small crystals and tabular crystals of vaterite and fibrous radial aggregates in the form of ooliths were found. In microscopic studies on sections of the stones, CaCO3 was localised mainly in the periphery in the form of layers or bands associated with calcium bilirubinate which was deposited in close relation to it. The phenomena contributing to the precipitation of CaCO3 are discussed, as is the importance of the latter in resistance to the pharmacologic treatment of gallstone disease. PMID- 3346535 TI - Chronic HDV (hepatitis delta virus) hepatitis. Intrahepatic expression of delta antigen, histologic activity and outcome of liver disease. AB - The expression of intrahepatic delta antigen (HDAg) was studied in relation to the morphologic features of HDV hepatitis and the outcome of liver disease. The study was performed in 101 patients followed up for an average of 12 years; one or more liver biopsies were available from each patient, giving a total of 167 specimens. The histologic features were assessed using numerical scores. A significant positive relation was observed between the number of HDAg-positive cells and the extent of portal inflammation (Spearman's rank coefficient 0.75). The highest degree of inflammation and intrahepatic expression of HDAg was found before the elimination of the virus, while the outcome of HDV disease was unrelated to the severity of the initial morphologic lesion. These results suggest that the individual immune response may play an important role in the pathogenesis of HDV hepatitis. PMID- 3346536 TI - Localization of urate oxidase in the crystalline cores of rat liver peroxisomes by immunocytochemistry and immunoblotting. AB - We investigated the immunocytochemical localization of urate oxidase by light and electron microscopy. Rabbits were immunized with urate oxidase prepared from rat liver and the resulting antibody was further purified by affinity chromatography. Immunoblotting of the antigen revealed a single band of Mr 32,500 daltons, consistent with a subunit of uricase. The same band was observed in immunoblots prepared from a total peroxisome fraction and in its subfraction containing the cores, but not in the matrix portion. Immunostaining of 1-micron sections with the antibody against uricase followed by protein A-gold-silver showed fine granules in hepatocytes, which exhibited distinct fluorescence when examined in a microscope equipped with epifluorescence illumination. Incubation of ultra-thin sections of rat liver, embedded in Lowicryl K4M, LR White, or Epon, with the anti uricase antibody followed by protein A-gold showed prominent labeling of the crystalline cores, with no reaction in the surrounding peroxisomal matrix. In contrast, the core region was spared whereas the matrix was heavily labeled in sections incubated with an antibody against catalase. Direct incubation of cores, isolated by centrifugation, with the anti-uricase antibody followed by protein A gold revealed gold particles on the surface of isolated cores, with rare particles within the lumen of the polytubular structures that make up the cores. Specificity of the immunolabeling was established in sections incubated with an IgG fraction from pre-immunized rabbits. These observations demonstrate that in normal rat liver urate oxidase is exclusively associated with the crystalline cores in peroxisomes. PMID- 3346537 TI - Cytochemical localization of blood group substances in human salivary glands using lectin-gold complexes. AB - We investigated localization of blood group antigens and their related substances in human labial salivary and submandibular glands by application of a post embedding cytochemical staining procedure using lectin- or glycoprotein-gold complexes. Surgical tissue was obtained from 10 patients. Blood group-specific lectins, such as Dolichos biflorus agglutinin or Helix pomatia agglutinin (group A-specific), Griffonia simplicifolia agglutinin-I B4 (group B-specific), and Ulex europaeus agglutinin I (group H-specific) could recognize A, B, and H antigens, respectively, only in mature secretory granules (mature SG), which were found preferentially in cells in the late phase of the maturation cycle. In immature secretory granules (immature SG), which were found in cells in the early or middle phase of the maturation cycle, no binding with these lectins was observed. The Golgi complexes and endoplasmic reticula also were not labeled with these lectins. In blood group O and B secretors, blood group antigens were uniformly distributed throughout all the mature SG examined. However, in blood group A secretors, the distribution was heterogeneous, i.e., in some granules only H antigen was demonstrated, whereas in others both A antigens and a small amount of H antigens were detected. Among the blood group-nonspecific lectins, wheat germ agglutinin (WGA) was found to bind more preferentially to immature SG than to mature SG. This was demonstrated irrespective of the blood group and secretor status of the tissue donor, except that in blood group A secretors WGA bound strongly to some mature SG which possessed A antigen. We discuss the significance of cellular and subcellular mosaic distribution of blood group antigens in connection with morphological differences of secretory granules and the maturation cycle of mucous cells. PMID- 3346538 TI - Immunohistochemical distribution of hepatic fatty acid-binding protein in rat and human alimentary tract. AB - Tissues from rat and human alimentary tract were immunostained with rabbit antibodies to fatty acid-binding protein (FABP) isolated from rat liver, since the precise immunohistochemical localization of the protein in gut has not been determined. The results obtained indicated that FABP immunoreactivity was found almost exclusively in intestinal absorptive cells, the sole exception being its presence in the cytoplasm of a few goblet cells. In small bowel, FABP-positive cells were most often found in the upper and middle segments, and less frequently in the lower to terminal portion. Immunoreactive cells were also found in large bowel of rat and human, but with differing patterns of distribution. In rat, positive cells were found mainly in the lower portion of the large intestine, whereas in human positive cells were present in all portions. Immunoreactive cells were detected in rat and human cecum, in the upper half of human rectum, and in human vermiform appendix. No such cells were found in esophageal and nonmetaplastic gastric mucosa or in pancreatic tissue, whereas they were present in great numbers in metaplastic gastric mucosa. The results of this study therefore suggest that FABP is a useful marker for research into the physiology or pathology of absorptive cells in the gastrointestinal tracts of both species. PMID- 3346539 TI - Occurrence and distribution of glycoconjugates in human tissues as detected by the Erythrina cristagalli lectin. AB - We applied a horseradish peroxidase-Erythrina cristagalli agglutinin (HRP-ECA) conjugate for histochemical staining of tissue sections from various formalin fixed, paraffin-embedded human tissue specimens. The HRP-ECA conjugate showed broad reactivity, but there was a distinct distribution of native (not masked by sialic acid) and sialic acid-masked ECA binding sites in the various organs. Free ECA binding sites could be detected on red blood cells, lymphocytes of thymus, tonsil, lymph node, and in mucous substances of different organs. Independent of blood group type, the vascular endothelium exhibited strong ECA reactivity. Free ECA binding sites occurred in the cytoplasm of Kupffer's cells in liver, in histiocytic cells of thymus, lymph node, tonsil, and in bone marrow. Podocytes of kidney glomerulus, syncytiotrophoblasts of placenta, megakaryocytes in bone marrow, myelin sheath of nerve, medullary thymocytes, and hepatocytes, as well as islet cells of pancreas, contained only sialic acid-capped ECA binding sites. Inhibiting studies with galactose, lactose, and N-acetyl-lactosamine, as well as other sugars, revealed that this lectin is specific for galactosyl residues. In comparison to galactose and lactose, N-acetyl-lactosamine exhibited the highest inhibitory activity on lectin binding, supporting the concept that this lectin is most reactive with N-acetyl-lactosamine-type (type 2 chain) glycoconjugates. PMID- 3346540 TI - The effect of three variables on adsorption of rabbit IgG to colloidal gold. AB - The purpose of this investigation was to (a) begin to evaluate the coagulation curve as a means of selecting the minimal quantity of IgG required to stabilize colloidal gold (Au); (b) determine the effect of the quantity of IgG added, the pH of adsorption, and the isoelectric point (pI) range of the IgG on the quantity of IgG bound and the stability of the IgG-Au complex with respect to desorption; and (c) discuss these results with respect to current theory on the effect of pH on adsorption of IgG to surfaces. No absolute minimal value required to prevent coagulation could be determined despite the high reproducibility of the values obtained; approximate values were selected. Each variable had an effect on the quantity of IgG bound: as the quantity of IgG added increased, the quantity bound increased; as the pH of adsorption became more alkaline, the quantity bound decreased; and as the pI range of the IgG became more alkaline, the quantity bound increased. IgG-Au complexes with a variable number of bound IgG molecules, depending on the three variables selected, can be produced. Production of IgG-Au composed of uniform numbers of IgG is discussed. A modification of the current theory on the effect of pH on adsorption of IgG is proposed. PMID- 3346541 TI - A new model of autoimmune disease. Experimental autoimmune uveoretinitis induced in mice with two different retinal antigens. AB - Experimental autoimmune uveoretinitis (EAU) is an organ-specific, T lymphocyte mediated autoimmune disease, which serves as a model for several human ocular inflammations of an apparently autoimmune nature. EAU pathology in some rodents and in monkeys can readily be induced by immunization with several different retinal proteins; however, advancing research into the cellular mechanisms of this disease has raised the need for an EAU model in an immunologically and genetically well defined species. We report here the induction of EAU in the mouse, which has hitherto been considered a species refractory to EAU, with two retinal Ag, the retinal soluble Ag and the interphotoreceptor retinoid-binding protein. Although all the mouse strains tested exhibited lymphocyte responses and antibody titers to both retinal Ag, EAU was inducible in only some of the strains, and the uveitogenic responses to retinal soluble Ag and interphotoreceptor retinoid-binding protein appeared to be mutually exclusive. The EAU model in mice was found to differ in several respects from the EAU model in other rodent species. Induction of the disease was achieved with a relatively high dose of Ag and an intensified immunization protocol, and the onset of disease was later, the duration was longer, and the course was less acute. Anterior segment involvement was slight or nonexistent, and damage to the retina and uvea was of a focal rather than of a diffuse nature. Murine EAU appeared to approximate some types of human uveitis more closely than the EAU models described in other rodent species with respect to its pathologic manifestations as well as its more chronic course. The relatively longer duration of the active stage of disease in murine EAU should facilitate therapeutic intervention in established disease, which was not feasible in the more acute models of EAU. The extensive knowledge of the immunologic parameters of the mouse and the availability of genetically defined strains should be of great value in the study of cellular mechanisms and immunogenetics of ocular autoimmune disease. PMID- 3346542 TI - Effect of gangliosides on activation of the alternative pathway of human complement. AB - Liposomes as defined model membranes were used to quantitatively study the effects of specific sialic acid containing glycolipids on activation of the alternative pathway of human C. Liposomes containing dimyristoylphosphatidylethanolamine, cholesterol, and cerebrosides at molar ratios of 1.0/0.75/0.33 activated the alternative pathway in human serum treated with MgEGTA. Activation was measured by C3 conversion and the deposition of total C3 and functional C3b on the liposome surface. The monosialoganglioside GM1, when incorporated into the activating liposome membrane at molar ratios between 10(-5) and 10(-2), inhibited activation in a dose-dependent manner. Sialosylparagloboside also inhibited activation in human serum, and inhibition was completely reversed after neuraminidase treatment. The degree of inhibition by GM1 correlated with the relative amount of GM1 exposed on the liposome surface. Sialic acid did not directly inhibit the binding of C3b when liposomes containing gangliosides were incubated with the purified components C3, B, D, and P. GM1 did inhibit activation when liposomes were incubated with a mixture of purified C3, B, D, P, H, and I. Binding assays with radiolabeled H showed increased binding of H to liposome-bound C3b in the presence of GM1. These results establish the ability of sialic acid on glycolipids to promote H binding to C3b and thereby regulate alternative pathway activation on a defined lipid membrane. PMID- 3346543 TI - Inhibition of the alternative pathway of human complement by structural analogues of sialic acid. AB - Liposomes were used to determine whether gangliosides containing certain structurally defined analogues of sialic acid could inhibit activation of the alternative pathway of human C. Gangliosides containing sialic acid residues with modifications in the N-acetyl group, carboxyl group, or polyhydroxylated tail were either isolated from natural sources or prepared by chemical modification of the native sialic acid structure. Sialic acid lost more than 90% of its inhibitory activity after removal of just the C9 carbon from the polyhydroxylated tail. Sialic acid was also unable to inhibit activation after converting the carboxyl group to a hydroxymethyl group. Galactose oxidase/NaB3H4 treatment of liposomes containing gangliosides with native or modified sialic acid residues confirmed that neither modification altered the amount of gangliosides exposed at the liposome surface. Changing the N-linked acetyl group to a glycolyl group had no effect on the inhibitory activity of sialic acid. These data further define the structural features of sialic acid that are important in regulation of alternative pathway activation. Both the C9 carbon of the polyhydroxylated tail and the carboxyl group are essential for this function; whereas, the N-linked acetyl group may be modified without loss of activity. PMID- 3346544 TI - Eosinophil granule major basic protein regulates generation of classical and alternative-amplification pathway C3 convertases in vitro. AB - Eosinophil major basic protein (MBP), a highly charged polycation, forms the core of the eosinophil granule and mediates tissue damage in allergic disease. Purified MBP was studied for capacity to regulate the generation of classical and alternative-amplification pathway C3 convertases because previous studies have shown that other polycations (protamine, poly-L-lysine) and polyanions (heparin) may play important roles in regulating C activation. MBP inhibited the generation of EAC1,4b,2a and EAC4b,3b,Bb,P but appeared to inhibit the generation of classical pathway convertase more than the alternative amplification pathway convertase at a given dose. Dose-response curves with MBP were steeper than curves seen with polyanion (heparin). MBP did not lyse cellular intermediates at concentrations that caused almost total inhibition of convertase generation. One mechanism of inhibition of convertase generation may have been through an action on C3b, because preincubation of MBP with an EAC4b,3b cellular intermediate interfered with the ability of this cellular intermediate to be lysed. Furthermore, MBP prevented consumption of B in a reaction mixture that contained factors B, D, and C3b, also suggesting an action on C3b. Reduced and alkylated MBP (A-MBP) was compared with native MBP, which possesses two reactive sulfhydryl groups, to determine whether charge alone is responsible for blocking convertase generation; native MBP rapidly associates and is relatively insoluble at neutral and alkaline pH whereas A-MBP remains soluble. A-MBP impaired convertase generation, did not appear to remain bound to cellular intermediates and did not suppress B consumption in the fluid phase assay. This suggests that the ability of MBP to regulate C activation is complex and not entirely through its net charge. Finally, although heparin or MBP alone may prevent C activation, when these substances were present at the same time there was no effect on C activation suggesting that charge neutralization may abrogate the effects of these charged substances on C activation. Taken together, these studies suggest that MBP at physiologic concentrations may regulate in vivo C activation at the tissue level. PMID- 3346545 TI - Subcutaneous and intestinal vaccination with tachyzoites of Toxoplasma gondii and acquisition of immunity to peroral and congenital toxoplasma challenge. AB - Mice were immunized s.c. or intraintestinally with two injections of a temperature-sensitive mutant of Toxoplasma gondii (ts4). Nonpersistence of the vaccine strain was documented by subinoculation of tissues of a subgroup of mice 3 mo or more after the second immunization. Mice were immune to other-wise lethal parenteral challenges with tachyzoites of the M7741 strain or to peroral challenge with bradyzoites of the Me49 strain of T. gondii. Although two s.c. or intraintestinal immunizations did not completely protect against development of T. gondii in the brains of mice, fewer cysts developed in the s.c. immunized mice than in control mice (2 +/- 3 cysts/0.01 ml in immunized mice compared with 75 +/ 48 cysts/0.01 ml in controls (p less than 0.002)). Reduction in cyst number after intraintestinal immunization was more variable, but also statistically significant (p less than 0.02). Female mice were first immunized, then mated, and then challenged perorally. Neonates of the s.c. immunized mice were not protected. Neonates of intraintestinally immunized mice were protected in part (36% of 115) against congenital infection compared with controls (7% of 107). PMID- 3346547 TI - Retention of platelet activating factor by human neutrophils. PMID- 3346546 TI - T cell receptor beta-chain genes in BW5147 and other AKR tumors. Deletion order of murine V beta gene segments and possible 5' regulatory regions. AB - The AKR thymoma BW5147 has rearranged both of its TCR beta-chain loci, using the same J beta region (J beta 2.5) in each, but with different V beta gene segments. Although the two rearrangements are expressed approximately equally in cytoplasmic RNA, the principle of allelic exclusion is maintained because only one rearrangement is in-frame and capable of encoding a functional protein. In hybridomas made with BW5147 as the fusion partner, this protein may combine with the alpha-chain protein derived from the normal cell to form new Ag/MHC specificities. An analysis of the sequences upstream from the BW5147 rearrangements and additional V regions suggests that two conserved sequences, 10 and nine nucleotides in length and located adjacent to each other 70 to 100 nucleotides 5' of the initiation codon, may be important in the expression of TCR beta-chain genes. Although B and T cells derive from common stem cells, no sequences are observed in T cells that are homologous to the octamer located 5' of all Ig genes. This implies that at least some of the sequences that regulate transcription are not shared in the two major types of lymphocytes. A survey of BW5147 and six other AKR thymomas using probes for 10 of the 18 known V region families indicates a distribution of V beta rearrangements in the tumors consistent with that found in thymocytes. Four of these tumors have apparent VDJ rearrangements on both chromosomes, with the deletion of other V beta gene segments. These data suggest that the primary mechanism of VDJ beta rearrangement is by looping out and excision of the intervening DNA and that most of the V regions are located 5' to the C region. These data were also used to develop a deletion order of the V beta gene segments in the TCR beta-chain locus. PMID- 3346548 TI - Role of C3 in humoral immunity. Defective antibody production in C3-deficient dogs. AB - Previous studies have shown that animals pharmacologically depleted of C3 have impaired antibody responses. However, such C depletion is neither complete nor sustained, and the C3 cleavage products generated by C3 depletion can both enhance and inhibit the immune response. To clarify the role of C3 in humoral immunity, the antibody response of dogs with genetically determined total deficiency of C3 (C3D) was examined. Serum IgG levels of the C3D animals were within the normal range, but were significantly lower than levels seen in normal controls or C3D heterozygotes. Specific antibody production was defective: the antibody titers of C3D dogs in response to primary intravenous immunization with two different T cell-dependent Ag (sheep E and bacteriophage phi X-174) were markedly reduced when compared to either normal controls or C3D heterozygotes. After secondary immunization with T-dependent Ag, the total antibody titers were normal, but the C3D dogs made proportionately more IgM and less IgG antibody than did either control group. After i.v. immunization with a T cell-independent Ag (DNP-Ficoll), the C3D dogs had reduced levels of IgM and IgG antibody after primary and secondary immunization. Neither i.m. immunization nor the use of a 20 fold increase in Ag dose i.v. could correct the defect seen in the antibody response of C3D dogs. The results herein demonstrate that C3 plays a critical role in the generation of a normal humoral immune response. PMID- 3346549 TI - Characterization of stage-specific antigens of infective larvae of the filarial parasite Brugia malayi. AB - Three stages of the filarial parasite Brugia malayi (infective third stage larvae, adult worms, and microfilariae) were analyzed for differences in their protein composition by two-dimensional gel electrophoresis. Comparison of protein profiles of the different stages showed both identical polypeptides (reflecting common proteins) and polypeptides specific for each stage. Three polypeptides present only in infective stage larvae were seen at 72 kDa at an isoelectric point (pI) of 4.98 (p72), 30 kDa at pI 5.5 (p30), and 22 kDa at pI 4.75 (p22). p72 could be labeled chemically with 125I by either chloramine T or IODO-GEN and biosynthetically with [3H]leucine and [35S]methionine during in vitro culture of live larvae; thus, p72 is most likely a surface protein of parasite origin. The antigenic composition of these polypeptides was elucidated by immunoblot analysis. Both p72 and p22 were recognized by hyperimmune rabbit sera to infective larvae; sera from rabbits immunized with adult worms, however, did not recognize any of these Ag. Sera from humans infected with the related Wuchereria bancrofti filaria recognized only p72 and not the other two polypeptides. It therefore appears that p72 is a stage-specific but not genus-specific Ag that is immunogenic in the infected host. p22 also appears to be stage specific and, because it is not recognized by W. bancrofti-infected sera, it may be either a species-specific Ag or a poorly immunogenic molecule of the parasite. With mAb raised to p72, p30, and p22, these proteins were shown to share several antigenic determinants when analyzed by immunoblotting. The shared epitopes were present on numerous molecules with a wide range of apparent m.w. in each of the different parasite stages. Thus, despite the apparent larval stage specificity of these molecules themselves, they must contain certain epitopes shared by molecules from other stages as well. The identification of the p72 polypeptide as a molecule with epitopes exposed on the surface of infective larvae provides a candidate Ag for testing as a protective immunogen. PMID- 3346550 TI - A novel method for the purification of sheep red cell rosetting lymphocytes. AB - A rapid, direct method for the purification of sheep red cell rosetting lymphocytes (ERFC) was developed. The whole procedure, including rosette formation, density separation and hemolysis could be completed within 10 min. A mixture of human peripheral blood mononuclear cells (PBMC) and 2 aminoethylisothiouronium bromide hydrobromide-treated sheep erythrocytes (EAET) was layered onto Ficoll-Paque without any pretreatment and centrifuged at 600 X g for 2.5 min. The pellet was then immediately treated with an NH4Cl solution containing 10% FCS and hemolysis was completed within 1 min. The purity of ERFC separated in one cycle of the procedure was 98%, the viability 99% and the yield 56% of the initial lymphocyte count. The re-rosetting ability of the prepared cells, after hemolysis, was 95%. The lymphocytes in the fraction prepared by the same method contained 94.3% CD2(OKT11)+ cells, 90% of which were CD3(OKT3)+ cells (T cells) and 9% were CD16(Leu11a)+ cells (NK cells). PMID- 3346551 TI - An ELISA for the detection of anti-acetylcholine receptor antibodies using biotinylated alpha-bungarotoxin. AB - An antibody-capture enzyme immunoassay has been developed for the detection of anti-acetylcholine receptor (AChR) antibodies in tissue culture supernatants using biotinylated alpha-bungarotoxin (B alpha BGT). Immunoglobulins in culture supernatants were bound indirectly to microtitre plates via an anti-globulin antibody already coupled to polyvinyl plates. Anti-AChR antibodies were then detected by incubation with AChR crude extract. Bound AChR was revealed by incubation with B alpha BGT followed by horseradish peroxidase-conjugated avidin. This assay is specific, more sensitive than the commonly used double antibody radioimmunoassay, avoids the use of radioactive material, is practical for large numbers of samples and is particularly suitable for detecting anti-AChR antibodies in tissue culture supernatants. PMID- 3346552 TI - An ELISA for the measurement of VP16 (etoposide) in unextracted plasma. AB - An ELISA for the anti-cancer drug VP16 in unextracted plasma has been developed using VP16-thyroglobulin-coated microtitre plates, a sheep anti-VP16 serum, and a donkey anti-sheep HRPO-labelled second antibody. The sensitivity of the assay was 0.5 ng/ml, providing a detection limit of 0.1 microgram VP16/ml plasma. Plasma interference effects were negligible and therefore the standard curve could be set up in assay buffer. A good correlation was obtained between the ELISA and established HPLC and RIA methods. No evidence was found of significant levels of cross-reacting metabolites in plasma samples obtained from patients receiving VP16 therapy. The antiserum did not cross-react with the epiaglycone of VP16. PMID- 3346553 TI - Rescue of hybrids from infected cultures. PMID- 3346554 TI - Fusion patterns of liposomes formed from stratum corneum lipids. AB - Stratum corneum lipid liposomes formed from epidermal ceramides (40%), cholesterol (25%), palmitic acid (25%), and cholesteryl sulfate (10%), when exposed to hypertonic medium, form flattened liposomes. Epidermal acylglucosyl ceramides (AGCs) and acylceramides (ACs) cause aggregation and fusion of these flattened vesicles. This could serve as a model to study (a) the fusion of membranous disks in the intercellular space of the stratum corneum and (b) the roles of AGCs and ACs in the assembly of lamellar structures in the epidermis. PMID- 3346556 TI - Chronic heliodermatitis: a morphologic evaluation of chronic actinic dermal damage with emphasis on the role of mast cells. AB - Descriptions of actinically damaged human dermis have focused on the late stages of elastotic degeneration. This has diverted attention from preceding events, which are important for understanding the sequence of pathologic changes that culminate in the deranged fibrous structures of elastotic dermis. We studied specimens from the back of the necks (exposed) and inner arms (unexposed) of 24 individuals, aged 35-84 yr, by light and transmission electron microscopy. Intense sunlight exposure was common to all. A previously undescribed finding was the presence of a perivenular, histiocytic-lymphocytic infiltrate in which numerous mast cells, often in close apposition to fibroblasts, were observed. We have termed this "chronic heliodermatitis." We postulate that mast cell-derived mediators in conjunction with enzymes released by the infiltrating cells lead to breakdown of elastic and collagen fibers. PMID- 3346555 TI - Fibroblasts induce the assembly of the macromolecules of the basement membrane. AB - The mechanism regulating the deposition of basement membrane components (BMCs) in a polymeric structure at the junction with the connective tissues is not yet understood. Cultures and cocultures of epithelial BMC-producing cells (L2 or PER cells) and fibroblasts were prepared in several experimental conditions and the organization of BMCs was studied by immunofluorescence. The pattern of BMCs in pure cultures of L2 or pulmonary epithelial rat (PER) cells consisted of intra- and extracellular granular deposits. At very high density, the cell contours were also underlined by a disrupted network of BMC deposits. A different fibrillar plexus--containing laminin, collagen type IV, and heparan-sulfate proteoglycan resistant to deoxycholate treatment and distant from the cell membrane--was observed in cocultures of L2 or PER cells with fibroblasts. Fibrils of fibronectin and/or collagen type I were most often dissociated from this plexus of BMCs. Similar results were obtained by adding a conditioned medium of L2 or PER cells to confluent fibroblasts, even when the cells were killed. Pure laminin also bound to the fibroblast layer. A coated film of fibronectin or polymeric collagen type I was unable to bind BMC provided by a conditioned medium. It is suggested that molecule(s) synthesized by fibroblasts and deposited in the pericellular matrix are involved in the assembly of BMCs. PMID- 3346557 TI - Differences in pyrimidine dimer removal between rat skin cells in vitro and in vivo. AB - Pyrimidine dimers, the most abundant type of DNA lesions induced by ultraviolet light (UV), are rapidly repaired in human skin fibroblasts in vitro. In the same cell type from rats, however, there is hardly any removal of such dimers. To investigate whether this low capacity of rat skin cells to repair lesions in their DNA is an inherent characteristic of this species or an artifact due to cell culturing, we measured the removal of UV-induced pyrimidine dimers from rat epidermal keratinocytes both in vitro and in vivo. Epidermal keratinocytes in vitro were unable to remove any dimers over the first 3 h after UV-irradiation, while only about 20% was removed during a repair period of 24 h. In this respect, these cells were not different from cultured rat fibroblasts. In contrast to the results obtained with keratinocytes in vitro, we observed a rapid repair of pyrimidine dimers in UV-irradiated keratinocytes in vivo over the first 3 h; this rapid repair phase was followed by a much slower repair phase between 3 and 24 h. These results are discussed in terms of the possibility that mammalian cells are able to switch from one DNA repair pathway to another. PMID- 3346558 TI - Glucocorticoid effects on contact hypersensitivity and on the cutaneous response to ultraviolet light in the mouse. AB - A single exposure to 254 nm ultraviolet irradiation (UV) can systemically suppress experimental sensitization to the simple allergen 2,4-dinitro, 1 chlorobenzene (DNCB) in the mouse. We show here that topical application at the site of irradiation of the 21-oic acid methyl ester derivative of the synthetic glucocorticoid triamcinolone acetonide (TAme) prevents UV suppression of sensitization. That is, mice painted with TAme at the site of UV exposure developed normal contact hypersensitivity (CH); mice exposed to UV only, like mice treated with the parent compound triamcinolone acetonide (TA), failed to be sensitized by DNCB applied to a distal site. TAme is inactivated rapidly by plasma esterases, so its effect is thought to be confined to the skin. Apparently, TAme blocked the cutaneous signal(s) for systemic suppression of CH. Histologically, irradiated skin exhibited mild inflammation and hyperproliferation, but these effects were greatly exaggerated and prolonged in the UV + TAme-treated skin, independent of sensitization at the distal site. The infiltrate consisted mostly of neutrophils and lacked the round cells characteristic of cell-mediated immunity. Apparently, normal immune suppression by UV prevented this vigorous reaction to irradiated skin. Applied together with DNCB. TAme blocked sensitization. It also prevented response to challenge by DNCB in previously sensitized animals. However, unlike the parent compound triamcinolone acetonide (TA), Budesonide or Beclomethasone diproprionate, each of which can penetrate the epidermis in active form, TAme had no effect on sensitization when applied at a distal site. Likewise, TAme did not affect plasma B (17-desoxycortisol) levels, whereas the other three compounds reduced plasma B tenfold, as expected of compounds causing adrenal-pituitary suppression. The results as a whole show that glucocorticoids can specifically inhibit cutaneous steps in induction of cell-mediated immunity or its suppression, and can, at the site of challenge, prevent its expression in CH. PMID- 3346560 TI - Increased protein kinase C activity in fibroblast membranes from psoriatic patients. AB - The activity of phospholipid/Ca2+-dependent protein kinase (PKc) was measured in the membrane and cytosolic fractions of normal and psoriatic human fibroblasts. The psoriatic fibroblasts displayed higher membrane-associated PKc activity than normal cells. In contrast, no significant difference in PKc activities was observed in cytosolic fractions from normal and psoriatic fibroblasts. These data suggest that PKc is preferentially associated with the membrane in psoriatic fibroblasts and that such elevated PKc activity in membranes may play a role in the pathogenesis of this disease. PMID- 3346559 TI - Thioredoxin reductase activity in Hermansky-Pudlak syndrome: a method for identification of putative heterozygotes. AB - Recent studies indicate that membrane-associated thioredoxin reductase (TR) is a possible regulator of melanin biosynthesis via the inhibition of tyrosinase by reduced thioredoxin. In normal individuals, the levels of TR activity in skin correlate linearly to the Fitzpatrick classification of skin type, being lowest in type I skin and highest in skin type VI. In this study, TR was measured in 3 mm skin biopsies in Hermansky-Pudlak syndrome (HPS) patients and their relatives. Forty-five individuals from seven Puerto Rican kindreds were tested, including 12 homozygotes, nine obligate heterozygotes, and 24 unclassified individuals. In addition, seven separate nonkindred HPS patients were tested. With one exception, TR activity was markedly decreased in 18 homozygotes. TR activity was decreased in eight obligate heterozygotes and in 12 unclassified kindred members, whereas 10 subjects had normal TR activity when compared to the expected activity of their skin type. Four individuals were excluded from the analysis because of inadequate controls for their age group or immunosuppressive treatment for kidney transplant. The results indicate that decreased TR activity assayed in 3-mm skin punch biopsies is a useful method for detecting carriers of the HPS gene. PMID- 3346561 TI - Determinants of morbidity and mortality due to acute respiratory infections: implications for intervention. AB - Acute respiratory infections (ARI) were monitored every two weeks in an urban community in Metro Manila, Philippines, to determine the incidence and risk factors for ARI morbidity. Hospitalized children with acute lower-respiratory tract infection (ALRI) were studied to determine case-fatality rates (CFR) and predictors for mortality. Incidence rates were highest in infants, 3.2-4.0 per person, followed by children one to four years of age, with corresponding rates of 3.0-3.4 per person. The risk factors for ARI morbidity were low socioeconomic status and age less than one year. A CFR of 5% in children with ALRI was observed. Malnutrition and a positive culture of blood were significant risk factors for mortality. These identified risk factors underscore the value of primary health care interventions, such as the standard ARI case management, immunization, health education, promotion of breast-feeding, and vitamin A supplementation, as strategies for reducing ARI mortality in developing countries. PMID- 3346562 TI - Acute respiratory illness among immunized and nonimmunized patients with high risk factors during a split season of influenza A and B. AB - A prospective survey of acute respiratory illness (RI) was made among 329 vaccinated and unvaccinated ambulatory patients with high-risk factors for influenza. Surveillance for virus during the influenza season revealed the predominance of influenza A and B in sequential periods. During the influenza A period, febrile RI was greatest among patients with chronic pulmonary disease; among 66 patients, vaccination significantly reduced RI. Age greater than 65 y (199 patients) and heart (90 patients) and metabolic diseases (151 patients) did not increase the relative frequency of febrile RI, and vaccine administration caused no apparent reduction in frequency of RI. During the influenza B period, no differences in RI were observed between the groups, and the frequency of RI was unrelated to vaccination. Variability in virus and vaccine specificities may have been important. Except for one subset of specific virus and host conditions, no overall reduction in influenza-like or total RI was observed from vaccinating ambulatory, high-risk patients. PMID- 3346563 TI - Strain-specific serum antibody responses in infants undergoing primary infection with respiratory syncytial virus. AB - We sought to characterize the human respiratory syncytial virus (RSV) subgroup specific antibody response to primary infection with RSV. RSV isolates from 43 infants and young children were typed as either subgroup A (Long strain-like) or B (18537 strain-like) based on reactivity with monoclonal antibodies. Acute-phase or preinfection and convalescent-phase sera were collected from the 43 subjects and tested in an enzyme-linked immunosorbent assay using purified F and G glycoproteins from RSV subgroups A and B and by neutralization assay against both subgroups of RSV. Twenty-six individuals had rises in titer of antibody to F glycoprotein, 27 to G glycoprotein, and 28 had rises in titer of neutralizing antibody. The antibody responses to homologous and heterologous F glycoproteins were not significantly different. In contrast, homologous vs. heterologous antibody responses to G glycoprotein were significantly different, with 7.3% relatedness between the G glycoproteins of subgroups A and B. Analysis of neutralizing antibody responses revealed 31% relatedness. PMID- 3346564 TI - Neutrophil adhesive dysfunction in thermal injury: the role of fibronectin. AB - We examined neutrophil substrate adherence in 19 subjects with burns involving 1% 83% of their body surface area. Within 24 h of injury, neutrophils from burn patients demonstrated a 50% reduction in adhesion to both gelatin and plastic substrates when stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), phorbol myristate acetate, and calcium ionophore A23187. Neutrophil substrate adherence examined as long as two weeks after burn injury remained abnormal. Neutrophils, from burn patients, stimulated with FMLP, phorbol myristate acetate, and calcium ionophore A23187 demonstrated a 51%, 37%, and 45% decrease, respectively, in release of immunoreactive fibronectin compared with control neutrophils. In neutrophils from burn patients there was a 31% reduction in total neutrophil-associated fibronectin compared with controls. The decrement in release and total cellular content of fibronectin in neutrophils from burn patients did not change when reexamined on day 7 after injury. The magnitude and time course of alterations in the cellular content and release of fibronectin correlate with adhesive dysfunction after burn injury. PMID- 3346565 TI - Purified capsular polysaccharide-induced immunity to Staphylococcus aureus infection. AB - In this study, we determined that immunization with capsular polysaccharide from Staphylococcus aureus could protect mice against nonlethal infections induced by encapsulated staphylococci. We immunized mice with either formalin-killed bacteria or purified capsular polysaccharide (PCP) and challenged them with one of three related S. aureus strains that varied in capsule size. Quantitative cultures of blood and kidney from the animals were performed to evaluate protection. Immunization with whole bacteria protected mice against infection with the homologous strain. Mice immunized with PCP were protected when challenged intravenously with either a highly encapsulated S. aureus strain or a microencapsulated mutant but not with an unencapsulated mutant. Protection correlated with capsular antibody levels in the immunized animals. Immunity to staphylococcal infection could be passively transferred to naive animals by using immune serum. These experiments suggest that the S. aureus capsular polysaccharide merits further study as a potential vaccine candidate for preventing staphylococcal infection. PMID- 3346566 TI - Staphylococcus aureus induces tissue factor expression in cultured human cardiac valve endothelium. AB - In vitro infection of cultured human cardiac valve endothelium (HCVE) with Staphylococcus aureus was used as a model to study potential mechanisms of vegetation formation in infective endocarditis. S. aureus was observed to adhere to and be ingested by HCVE. Infection for 8 h resulted in increased levels of procoagulant activity in HCVE, shown to be tissue factor by a specific assay. Mean activity in infected HCVE was 662 +/- 149 (mU/10(5) HCVE +/- 1 SD) versus 221 +/- 78 in control HCVE; surface-expressed activity was 57 +/- 25 in infected monolayers and undetectable (less than or equal to 10) in controls. Bacteria alone had no activity. These results suggest that endothelium may have a functional role in the pathogenesis of S. aureus endocarditis and may provide one potential mechanism for activating coagulation to initiate vegetation formation on a colonized cardiac valve. PMID- 3346568 TI - Comparison of synthetic antigens for detecting antibodies to phenolic glycolipid I in patients with leprosy and their household contacts. AB - Three synthetic antigens related to the natural antigen phenolic glycolipid I (PGL-I) were compared for their efficacy in detecting leprosy when used as antigens in an enzyme-linked immunosorbent assay (ELISA) for IgM antibody to PGL I. Absorbance values for ELISAs using the three antigens correlated well (.79 less than r less than .99) and had a high rate of agreement (89.5% less than a less than 98.4%). Of three subjects (household contacts of patients with leprosy) who later developed the disease, one with lepromatous and one with indeterminate leprosy were seropositive by ELISAs using the three antigens before the clinical onset of disease; one who developed borderline tuberculoid leprosy was seronegative. The predictive value of a positive result for the test was very low (less than 2.4%) and the predictive value for a negative result was high (greater than 99.9%) because of the low prevalence of leprosy in French Polynesia (1.78 per 1000). The high sensitivity, specificity, and efficiency of the tests using the three antigens confirmed their great value for serodiagnosis of leprosy, especially the multibacillary form; the ELISA using NTP seems to be more specific and sensitive for detecting the paucibacillary form. PMID- 3346567 TI - Serious infections due to penicillin-resistant strains of viridans streptococci with altered penicillin-binding proteins. AB - We investigated the mechanism of resistance to penicillin in two penicillin resistant clinical isolates of viridans streptococci that caused life-threatening infections in two patients not receiving chronic penicillin therapy. The first was a strain of Streptococcus intermedius that was isolated from the cerebrospinal fluid of a patient with post-neurosurgical meningitis. The second was a strain of Streptococcus mitis recovered from the bloodstream of a leukemic patient with neutropenia. Both patients failed to respond to penicillin. The mechanism of resistance in these strains was associated with diminished affinity for penicillin of their penicillin-binding proteins, as compared with those of penicillin-susceptible control strains. We conclude that penicillin-resistant viridans streptococci may cause serious infections even in patients not receiving chronic penicillin therapy, that this resistance is clinically significant and may result in failure of penicillin therapy, and that the mechanism of resistance in these strains is associated with diminished affinity of the penicillin-binding proteins for penicillin. PMID- 3346569 TI - Effect of age on the frequency of active Campylobacter pylori infection diagnosed by the [13C]urea breath test in normal subjects and patients with peptic ulcer disease. AB - We studied the frequency of active Campylobacter pylori infection in persons from North America (n = 53) or the People's Republic of China (n = 15) who had no gastrointestinal symptoms or a history of ulcer disease and in patients with active or recently active duodenal or gastric ulcers diagnosed by endoscopy (n = 105). C. pylori infection was significantly (P less than .001) more frequent in patients with peptic ulcers (88%) than in the normal group (45%). An age-related increase in the frequency of C. pylori infection in subjects with no gastrointestinal symptoms paralleled the known age-related increase in prevalence of gastritis. The frequency of C. pylori infection in patients with duodenal ulcers was greater than 80%, irrespective of age. C. pylori infection was more common in the Chinese group (age, 20-39 y) than in the North American group of the same age (60% vs. 24%). Association of C. pylori with specific diseases should not be inferred without knowing the prevalence of C. pylori infection in reference populations of the same age and ethnic background. PMID- 3346570 TI - Markers of cell-mediated immunity after vaccination with an inactivated, whole cell Q fever vaccine. AB - A clinical trial of Q fever vaccine in four South Australian abattoirs showed apparently complete protection against natural infection; however, only 50%-60% of vaccinees developed complement-fixing or immunofluorescent antibody after vaccination. Cell-mediated immunity to Coxiella burnetii antigens, as measured by an index of lymphoproliferative responses (LSI) of peripheral blood mononuclear cells, was therefore assessed. Eighty-five percent of 13 subjects with "low risk" of exposure to Q fever and with an initially negative LSI converted to a positive LSI after vaccination; conversion was noted nine to 13 days after vaccination, and positive values were obtained for at least 96 d. Only 35% of this group seroconverted. In a "high-risk" group (abattoir workers), higher rates of positive LSI (greater than 95%) and of antibody (50%-70%) were observed after vaccination; greater than 95% of vaccinees in this group, who had been vaccinated five years previously, had positive LSI values. PMID- 3346571 TI - Acute antibody responses to Giardia lamblia are depressed in patients with AIDS. AB - We investigated the ability of patients with AIDS to develop antibody responses to a naturally encountered antigenic stimulus, Giardia lamblia. Using an enzyme linked immunosorbent assay to detect IgG, IgM, and IgA to G. lamblia trophozoites, we tested sera from 29 patients with AIDS (15 without and 14 with G. lamblia infection); 20 healthy homosexual men; and 91 immunocompetent heterosexual subjects, 25 of whom were infected with G. lamblia. Heterosexual subjects infected with G. lamblia had significantly higher levels of all three classes of specific antibody than did the uninfected subjects (P less than .0001). Patients with AIDS who had acute symptomatic giardiasis had significantly lower levels of all antibodies than did the heterosexual subjects who had giardiasis; specific IgM was absent in all but one patient with AIDS. The symptomatically infected patients with AIDS had low levels of G. lamblia-specific antibodies that were similar to those of the uninfected patients with AIDS. Patients with AIDS do not have to suffer from prolonged symptomatic G. lamblia infections, however, because available therapy is effective against the parasite, independent of a patient's immune status. PMID- 3346572 TI - Antibody responses in early human immunodeficiency virus type 1 infection in hemophiliacs. AB - Sera from hemophiliacs were analyzed for antibodies to human immunodeficiency virus type 1 (HIV-1) by using radioimmunoprecipitation (RIP), western blotting (WB) with nonreducing buffer (NR), and WB with reducing buffer (R). We analyzed envelope gp160, gp120, and gp41; pol gene proteins p64, p53, and p34; and gag gene protein p24. Of 215 samples positive for reactivity to gp160 and gp120(RIP), antibodies to p24 were undetectable in 2 (0.9%), to gp41 in 9 (4.2%), to the pol antigens in 5 (2.3%), to gp120(NR) in 3 (1.4%), and to gp120(R) in 55 (25.6%). By sequential analysis of samples, antibodies to gp120(NR), gp120(R), p24, gp41, p64/53, and p34 were observed later in the course of infection than were antibodies to gp120(RIP) or gp160. This result suggests caution against reliance on WB as the "gold standard." A significantly higher rate of progression to AIDS related complex was found for individuals lacking antibodies to gp120(R). It is possible that antigenic domains represented by gp120(R) may play a role in the pathogenesis of HIV-1 infection. PMID- 3346574 TI - The rapid diagnosis of leptospirosis: a prospective comparison of the dot enzyme linked immunosorbent assay and the genus-specific microscopic agglutination test at different stages of illness. PMID- 3346573 TI - Simultaneous detection of antibody to the human immunodeficiency virus and of the surface antigen of hepatitis B virus in human serum. PMID- 3346576 TI - Demonstration of plasmids in Campylobacter pylori. PMID- 3346575 TI - A food-borne outbreak of Giardia lamblia. PMID- 3346577 TI - Natural killer cell activity as a prognostic parameter in the progression to AIDS. PMID- 3346578 TI - Clostridium tertium bacteremia in a patient with aspiration pneumonia: an elusive diagnosis. PMID- 3346579 TI - Final report of the NCI Hyperthermia Equipment Evaluation Contractors' Group- Part I. PMID- 3346580 TI - Introduction to hyperthermia device evaluation. AB - From 10/81 to 1/87, the National Cancer Institute (NCI) of the U.S. Department of Public Health Services (PHS) contracted with four institutions to evaluate hyperthermia technology to be applied in the treatment of human malignancy. During the five year period 1981-1986, data were collected which now reside in a consensus database representing treatments of 792 separate sites or fields in a total of 573 patients. These patients were treated with one or more of 49 devices by the four institutions. Sixteen ultrasound (US) devices were evaluated in 195 sites. Nine magnetic induction (MI) devices were evaluated in 208 sites. Twenty radiative electromagnetic (EM) devices were evaluated in 488 sites. Four interstitial (IRF) devices were evaluated in 37 sites. Many sites were treated with multiple hyperthermia modalities. This first in a series of 13 reports describes the general objectives of the Contractors' Group, basic methods of device evaluation and brief details of the large variety of devices tested. PMID- 3346582 TI - CDRH RF phantom for hyperthermia systems evaluations. AB - The National Cancer Institute (NCI) sponsored clinical evaluations of investigational 'regional' hyperthermia systems at four clinical institutions. To support this project, the Center for Devices and Radiological Health (CDRH) developed a series of test instruments to evaluate the magnitude and repeatability of the induced heating by radiofrequency (RF) systems. Data from three institutions using the same model hyperthermia system have been analyzed. After heating, the average temperature from measurements taken at several points in the test phantom at each institution agree within +/- 0.002 degrees C. These differences are about equal to the measurement uncertainty. Thus, this technique can be used for preclinical evaluation and quality control of the total system operation. After one of the institutions relocated its hyperthermia system, a subsequent set of data showed inconsistencies compared to their earlier data. Investigation traced this to cable loss and power meter interference. From the analysis of the data from the three institutions, the utility of the CDRH RF phantom for hyperthermia systems evaluation is demonstrated. PMID- 3346581 TI - Phase I evaluation of hyperthermia equipment--University of Utah institutional report. AB - At the University of Utah Medical Center the thrusts of the effort with respect to the NCl Hyperthermia Equipment Evaluation Contract have been threefold. The first objective was the development of a reliable thermometry system for collecting temperature information as a function of space as well as time. The second objective was the evaluation and comparison of a number of hyperthermia devices, particularly with respect to deep-heating devices, and specifically as pertains to the BSD annular phased array system (AA) and its various configurations. The third objective was to develop methodology for analysing hyperthermia data which could be easily adapted toward device comparison. In the period from 10/81-1/86, a total of 137 patients were treated with one or more of 10 devices, totalling 199 device evaluations at the University of Utah Medical Center or the subcontracting institution, LDS Hospital. Of these, 132 device evaluations involved deep-seated tumours. The AA was found to be feasible for deep pelvic regional hyperthermia, although the frequency of reversible acute toxicity was high, and achievement of desired temperatures was frequently limited by one of several factors. The radiative electromagnetic wave applicators which were evaluated for treatment of superficial tumours were found to be mostly feasible for tumours of the thoracic and extremities regions, although the heating patterns were frequently too shallow or too small in area, when compared with the size of the lesion. PMID- 3346583 TI - Hyperthermia quality assurance results. AB - The Hyperthermia Physics Center (HPC), under contract with the National Cancer Institute (NCI), has conducted review-type quality assurance (QA) measurements at the five Hyperthermia Equipment Evaluation Centers involved in evaluating the clinical efficacy of a variety of devices for delivering heat treatments to deep seated human tumours. A summary of the QA protocol, results, testing procedures, standards, criteria, conclusions and recommendations are presented in this paper. The QA review measurements indicate (a) that 81.5 per cent of temperatures surveyed were within the 0.2 degrees C HPC criterion (91 per cent were within 0.4 degrees C), (b) that only 66 per cent of power indications were within the 10 per cent criterion, (c) that the heat patterns in a phantom produced by the BSD Annular Phased Array (AA) had significant variability, (d) that each treatment facility had at least a few potentially occupiable locations where the maximum permissible American National Standards Institute standards of electromagnetic leakage were exceeded, and (e) that these levels of accuracy and safety were achieved only after stringent inhouse QA efforts. From the combined data, it is concluded that the temperature accuracy in this cooperative trial was sufficient to justify a common analysis of clinical data as presented in this series. Also, stringent quality control of every parameter must continue to be stressed in all future hyperthermia trials. PMID- 3346584 TI - Evaluation of equipment for hyperthermic treatment of cancer. PMID- 3346586 TI - Lateral sinus pathology (22 cases managed at Groote Schuur Hospital). AB - One hundred and thirty patients with acute and acute on chronic mastoiditis were managed at Groote Schuur Hospital between 1980 and 1984. Twenty-two (16.9 per cent) had pathology of the lateral (sigmoid) sinus and 19 of these patients had cholesteatomas. Nine patients (40.9 per cent) had concomitant intradural sepsis and there were two deaths. The modern literature is reviewed and the pathology, presentation and management of lateral sinus pathology is discussed. This condition is rare and clinical features may range from subtle signs to gross toxaemia, torticollis and evidence of septic embolization. The otolaryngologist must be competent in diagnosing and treating this condition in all forms of its wide spectrum of presentation. PMID- 3346585 TI - Stanford University institutional report. Phase I evaluation of equipment for hyperthermia treatment of cancer. AB - From September 16, 1981, through April 4, 1986, a total of 21 radiative electromagnetic (microwave and radiofrequency), ultrasound and interstitial radio frequency hyperthermia applicators and three types of thermometry systems underwent extensive phantom and clinical testing at Stanford University. A total of 996 treatment sessions involving 268 separate treatment fields in 131 patients was performed. Thermal profiles were obtained in 847 of these treatment sessions by multipoint and/or mapping techniques involving mechanical translation. The ability of these devices to heat superficial, eccentrically located and deep seated tumours at the major anatomical locations is evaluated and the temperature distributions, acute and subacute toxicities, and chronic complications compared. Average measured tumour temperatures between 42 degrees C and 43 degrees C were obtained with many of the devices used for superficial heating; average tumour temperatures of 39.6 degrees C to 42.1 degrees C were achieved with the three deep-heating devices. When compared to the goal of obtaining minimum tumour temperatures of 43.0 degrees C, all devices performed poorly. Only 14 per cent (118/847) of treatments with measured thermal profiles achieved minimum intratumoural temperatures of 41 degrees C. Fifty-six per cent of all treatments had associated acute toxicity; 14 per cent of all treatments necessitated power reduction resulting in maximum steady-state temperatures of less than 42.5 degrees C. Direct comparisons between two or more devices utilized to treat the same field were made in 67 instances, including 19 treatment fields in which two or more devices were compared at the same treatment session. The analyses from direct comparisons consistently showed that the static spiral and larger area scanning spiral applicators resulted in more favourable temperature distributions. Three fibreoptic thermometry systems (Luxtron single channel, four channel and eight channel multiple [four] probe array), the BSD Bowman thermistor system and a thermocouple system were evaluated with respect to accuracy, stability and artifacts. The clinical reliability, durability, and patient tolerance of the thermometry systems were investigated. The BSD Bowman and third generation Luxtron systems were found clinically useful, with the former meeting all of our established criteria. PMID- 3346587 TI - Thermal myringotomy (an alternative to grommet insertion in childhood secretory otitis media?). AB - Thirty-six children with bilateral secretory otitis media were treated by thermal myringotomy and middle ear aspiration in one ear, and conventional myringotomy, middle ear aspiration and Shepard grommet insertion in the other ear. All children underwent adenoidectomy. Comparing the effectiveness of the two different procedures over a three-month review period, our main findings are as follows. All thermal perforations were closed by 42 days. Elimination of middle ear fluid was achieved in 81 per cent of the thermal myringotomy group, and in 100 per cent of the grommet group. While there was no significant difference in the hearing improvement between the procedures, conventional myringotomy and grommet insertion provided significantly better sustained middle ear ventilation. PMID- 3346588 TI - Serous otitis media in malignancies of the nasopharynx and maxilla. PMID- 3346589 TI - Early diagnosis of tuberculous otitis media. AB - In an area endemic for pulmonary tuberculosis, 23 of 192 histological specimens from chronic suppurative otitis media proved to be tuberculous. A personal or family history of tuberculosis was present in 75 per cent of the patients. A pre operative diagnosis was made in six out of 23 patients, but middle ear mucosal biopsy and aural polypectomy provided a histological diagnosis in 30 and 35 per cent respectively. It is suggested that, when tuberculosis of the middle ear is a possibility, initial surgery for chronic suppurative otitis media should be minimal and directed towards obtaining a tissue diagnosis. PMID- 3346590 TI - The styloid process in ossicular chain reconstruction (a pilot study). AB - Our pilot study reports twenty-six cases of resolved chronic otitis media in which the human, cadaveric styloid process was used as an ossicular graft material. A maximum follow-up of one year is presented in this paper. There was no extrusion or rejection of the styloid processes. Hearing improvement with a closure of the air-bone gap to within 10-15 dB. of the pre-operative bone conduction was found in most cases. So far the styloid process has proved to be an ideal ossicular graft though the long-term results are yet to be seen. PMID- 3346591 TI - The branchio-oto-renal syndrome (report of two family groups). AB - The major features of the Branchio-Oto-Renal syndrome (BOR syndrome), an autosomal dominant disorder, are branchial remnants, ear anomalies, deafness and renal dysplasia. We report two family groups affected by the BOR syndrome: in two thirds of the affected children renal abnormalities led to severe renal insufficiency in early life. The necessity for a meticulous search for renal anomalies in individuals with aural and/or branchial abnormalities is emphasized. In affected families, genetic counselling is suggested. PMID- 3346592 TI - Why you should have a hearing therapist. PMID- 3346593 TI - The effect of inferior turbinate outfracture on nasal resistance to airflow in vasomotor rhinitis assessed by rhinomanometry. AB - Twenty-eight patients with nasal obstruction due to vasomotor rhinitis were assessed using anterior rhinomanometry before and six weeks after the operation of out-fracture and amputation of the posterior ends of the inferior turbinates. It was found that the operation did not significantly improve the nasal airway. Though just over half the patients had an objective improvement in nasal airflow, only half of this group reported a subjective improvement in their symptoms. PMID- 3346594 TI - An improved stent for use in the surgical management of congenital posterior choanal atresia. AB - The advantage of Foley catheter stenting for choanal atresia are that: 1. It is well tolerated by the patient. 2. It is simple to introduce, fix and remove. 3. It minimizes septal or columellar necrosis. 4. It minimizes nasal cavity and paranasal sinus infection. 5. It is adjustable in that pressure on the choanal walls can be controlled by inflation or deflation of the balloon as necessary. 6. It is easy to fix in cases of unilateral atresia. To date the use of this method has been uniformly satisfactory, without complications. PMID- 3346595 TI - Globus pharyngeus (Part I). PMID- 3346596 TI - CT sialography and conventional sialography in the evaluation of parotid gland neoplasms. PMID- 3346597 TI - Middle ear effusions and myasthenia gravis. AB - A case of ME effusion in a patient with MG is reported. The likely pathogenesis is of TVP muscle weakness causing Eustachian tube dysfunction. ME effusion should be suspected in a myasthenic complaining of sudden hearing loss. Tympanometry with measurement of the ME pressures and reflexes is a useful tool for assessing a myasthenic's response to treatment. PMID- 3346598 TI - Fibrous dysplasia of the temporal bone. AB - A 38-year-old woman with fibrous dysplasia of the entire right half of the mandible and the right temporal bone is presented. She had a unilateral progressive conductive hearing loss and stenosis of the auditory canal complicated by a chronic external otitis, a hidden cholesteatoma, destruction of the ossicles and an impending facial palsy. Surgery was performed to create a new auditory canal, to eradicate the cholesteatoma and to decompress the facial nerve from the surrounding fibrous dysplasia. PMID- 3346599 TI - Exostosis of the internal auditory canal. AB - Although exostoses of the external auditory canal are not uncommon, those of the internal canal are extremely rare. One of these is described occurring in a 53 year-old man whose rapidly progressive hearing loss was without any associated abnormality. PMID- 3346600 TI - An unusual complication of epistaxis. AB - Ten days after left-sided external carotid artery ligation for control of profuse epistaxis a complete left-sided facial nerve palsy developed in a 25-year-old male. Abnormal bleeding or clotting disorders had been excluded. It is postulated that either thrombosis or embolus obstructed the petrosal branch from the middle meningeal artery on the same side with subsequent ischaemia resulting in nerve degeneration of the intratemporal portion of the facial nerve. PMID- 3346602 TI - Nasopharyngeal cyst (report of eight cases). AB - Eight cases of nasopharyngeal cyst are reviewed. Five were asymptomatic. Marsupialization of the cyst provided adequate treatment in the three symptomatic cases. PMID- 3346601 TI - Maxillary chondrosarcoma (report of two cases). AB - Two cases of chondrosarcoma of the maxilla are reported together with the clinical and histological differential diagnosis. The origin of this rare tumour in the maxilla, a bone with exclusive membranous ossification, is discussed in accordance with the new concept of cell differentiation in neoplasia. PMID- 3346603 TI - Nasopharyngeal carcinoma complicated by pseudohypertrophic osteoarthropathy. AB - This paper describes a case of nasopharyngeal carcinoma complicated by pseudohypertrophic osteoarthropathy due to pulmonary metastasis following radiotherapy. A similar clinical picture may be seen in pseudohypertrophic osteoarthropathy, rheumatoid arthritis and carcinomatous arthritis. It is important clinically to differentiate them from one another. One should search carefully for an intrathoracic secondary lesion when pseudohypertrophic osteoarthropathy occurs in a case of nasopharyngeal carcinoma following radiotherapy. PMID- 3346604 TI - NED survival in head and neck cancer (post-mortem correlations). AB - A common feature of reporting head and neck squamous cancer statistics in recent years has been to consider patients dying with no evident disease (NED) as successfully treated. We present two patients who died with no clinically evident squamous cancer and who could therefore have been reported as cured but for autopsy findings which showed significant distant spread. These findings are supported by several reports of distant metastases in squamous head and neck cancer and it is suggested that rates of post-mortem examinations be included in survival figures in the future. PMID- 3346605 TI - Comprehension of proverbs by average children and children with learning disorders. PMID- 3346606 TI - Knowledge, perception, and performance of assertive behavior in children with learning disabilities. PMID- 3346607 TI - A comparison of intellectually superior male reading achievers and underachievers from a neuropsychological perspective. PMID- 3346608 TI - The relationship between neuropsychological/perceptual performance and socioeconomic status in children with learning disabilities. PMID- 3346609 TI - The effectiveness of textbook adaptations in life science for high school students with learning disabilities. PMID- 3346610 TI - Using a demonstration strategy to teach midschool students with learning disabilities how to compute long division. PMID- 3346611 TI - Parent participation in the initial placement/IEP conference ten years after mandated involvement. PMID- 3346612 TI - Learning disabilities teachers' perceptions of educational programs for adolescents with learning disabilities. PMID- 3346613 TI - The prediction of good and poor reading before kindergarten entry: a nine-year follow-up. PMID- 3346614 TI - [Peroperative measurement of peripheral vascular resistance. Significance for the indications, technic and prognosis of distal bypasses. Apropos of 35 cases]. AB - The authors report their experience of the per-operative measurement of the "absorption capacity" of a distal vascular network. This constitutes an absolute measurement and provides a reliable per-operative indication of a bypass, and eventually that of surgical reintervention in early thrombosis. The techniques are described with a brief overview of the major physical laws in this field. As a predictive test, the measurement is highly reliable, and a threshold value of 3 PRU was found in the series; beyond this value, all bypasses were thrombotic. A brief survey of the literature considers the theme of peripheric resistances. A table of clinical indications is situated at the end of the study, and is related to values of residual pressure and peripheric resistance. Glossary: R: peripheral resistance PAF: Pressure in femoral artery P: Pressure (mmHg) Pr: residual pressure Rp: Physiological resistance RS: stenotic resistance RC: Resistance due to collateral flow D: Femoral flow d and d': successive variations of flow. PMID- 3346615 TI - [Recurrent thrombosis of an aortic valve prosthesis in a pregnant woman. Treatment with urokinase]. AB - A 36 year old woman developed two thromboses on aortic valve prosthesis. The first thrombus at the 14th week of pregnancy was treated with urokinase (2,000 U/kg/h) plus heparin (700-1,000 U/h) over 24 hours and normal wing kinetics were obtained. The second thrombus developed at the 36 th week of pregnancy when the patient was receiving calciparin, and only transient improvement was obtained with similar doses of urokinase hourly over 72 hours. Progressive worsening resulted in higher doses (4,000 U/kg/h) being given without heparin and the thrombus then resolved. The use of urokinase for the first time in this indication allowed therefore, on two occasions and without hemorrhagic complications the cure of this recurrent thrombosis on aortic prosthesis, and the birth, by caesarean, of a healthy baby. PMID- 3346616 TI - [Intermittent arterial claudication. Clinical aspects--hemodynamic correlation]. AB - INTRODUCTION: Intermittent arterial claudication is the master symptom in lower limbs arteriopathy. It is used as a reference in invasive or non-invasive arterial explorations. It allows to assess the evolutive degree of the disease and above all helps the therapeutic decision. The seat of claudication is traditionally acknowledged as being located immediately downstream of the significant arterial lesion. The purpose of our work was to verify such a notion and ascertain the relation between spontaneous and tread-mill induced claudication. PROTOCOL: 60 stage-2 arteritic patients were included in a prospective mode study. They were all taken in hospital for arteriographic check up and vascular functional explorations: Doppler velocimetry, segment pressures, treadmill tests and pressure measurements after stress. The patients were classified according to age (table I), time of claudication record (table II) and lesions location (table III). All clinical and paraclinical data were recorded with a view to correlations interpretation. RESULTS AND DISCUSSION: The relation between spontaneous claudication and tread-mill induced claudication was studied with respect to lesion sites (table IV). Among 37 patients 46% of the claudications observed appeared at iliac stage in both cases (fig. 1). In 35 cases, femoral claudication was observed in 48% (fig. 2). As for distal claudication among 6 patients, 3 showed calf claudication in both cases, i had foot claudication and 2 showed discrepant claudication types. The relation between claudication and lesion site was not confirmed in all cases. Buttock claudication always appeared in relation with a lesion upstream or an internal iliac lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346618 TI - [Reestablishment of the clinical diagnosis in vascular acrosyndromes]. AB - Raynaud's phenomenon (RP) is very frequent with a prevalence of 4% in a general population. Its evaluation has to be simple noninvasive and cheap. The only difficulty is to differentiate early primary RP from secondary RP that may evolve principally to a connective tissue disorder. Two questions have to be solved 1- Is it a primary or a secondary RP? 2--In case of secondary RP how to obtain a more precise diagnosis? Clinical examination alone is able to give a response for question 1 with 76% of reliability. Information has to be collected about sex, age at onset, occupation, uni or bilaterality of the disability, thumb involvement and drug consumption. Physician has to examine skin carefully, pulses, arterial bruits, heart, lungs, the time of return of color of digits after squeezing the blood out of the hand by clenching with and without compression of the radial and/or the cubital artery. Inquiries should be made about visceral involvement: oesophageal dysfunction, dyspnea, sicca syndrome, thyroiditis or polyneuritis that rule out a primary form of Raynaud's phenomenon. PMID- 3346617 TI - [A misunderstood treatment for hyperhidrosis: ionization. Principles, material, methodology, early results]. AB - Based on a new and specific apparatus developed by one of the authors, an original method of treatment of palmoplantar hyperhidrosis, either essential or associated with acrocyanosis, is described in detail. The extremities to be treated are placed in tanks containing tap water ensuring conduction fo current between epidermis and electrode. The recommended current of 20 milli-amperes is obtained by adjustment of a potentiometer. Treatment sessions (20 minutes for hands or feet, 40 for all four extremities) take place with a well defined frequency: 3 the first week, 2 the second, I the following two weeks. Maintenance sessions are necessary when sweating recurs. In a longitudinal series of 29 patients, 28 (96.5%) were significantly improved. From the 5th session onwards, the decrease in hyperhidrosis was evaluated by patients as very pronounced in 5 cases (17.2%) and as complete in 21 cases (72.5%). In 5 of the 6 patients with hyperhidrosis associated with acrocyanosis, the patients reported attenuation of cyanotic coloration of skin and relative warming up of extremities treated. Tolerance was excellent in 28 cases, incidents being rare and minor. Patients with pacemakers cannot be treated by this method. PMID- 3346619 TI - [Prognostic value of modifications in the blind spot in women taking contraceptives]. PMID- 3346620 TI - [Chemical sympatholysis guided by computerized scanning]. PMID- 3346621 TI - Estimation of indifference points with an adjusting-delay procedure. AB - In a series of conditions, pigeons chose between 1.5 s and 3 s of access to grain, each preceded by some delay. The delay that preceded the small reinforcer was constant throughout a condition. The delay that preceded the large reinforcer was increased or decreased a number of times each session in order to estimate an "indifference point," a delay at which the subject chose each alternative about equally often. The experiment was designed to determine whether variations in any of four features of this adjusting-delay procedure would systematically alter the estimated indifference points. The four features were the total trial duration, the number of center-key responses necessary to begin a trial, the number of choice trials that preceded each change in the adjusting delay, and step size- the size of each increment and decrement in the delay. Manipulation of the first three features had no systematic effects on the indifference points. As step size was increased from 0.5 s to 6 s, within-session variability of the adjusting delay steadily increased, and the 6-s step size produced larger indifference point estimates for some subjects. The results suggest that, within certain limits, these procedural features can be altered without affecting the indifference-point estimates, but that the use of a large step size can distort the estimates. Some theoretical implications of the relative constancy of indifference points across these procedural variations are discussed. PMID- 3346622 TI - Establishing auditory stimulus control over an eight-member equivalence class via conditional discrimination procedures. AB - Two eight-member equivalence classes of visual stimuli were established during three phases of a training program. In Phase 1, two training arrangements were compared. In one, 3 subjects were taught on different trials to select from a single pair of comparison stimuli (A1, A2) in response to eight sample stimuli that were trained in pairs (B1, B2; C1, C2; D1, D2; E1, E2). In the second arrangement, subjects were taught to select from four pairs of comparisons (B1, B2; C1, C2; D3, D2; E2, E2) in response to two samples (A1, A2). Training with the single pair of comparison stimuli resulted in the development of equivalence relations (B1C1, B2C2, D1B1, D2B2, B1E1, B2E2, C1D1, C2D2, C1E1, C2E2, D1E1, D2E2, and their reciprocals) between the sample stimuli without direct training of these relations. In the other training arrangement, these relations among the comparison stimuli developed in the performance of 1 subject only. In Phase 2, three new pairs of stimuli (F1, F2; G1, G2; H1, H2) were substituted for three of the original pairs (B1, B2; C1, C2; D1, D2) and the training arrangements for the groups were reversed. Following training, the performances that showed equivalence relations on the probes in the first phase also showed equivalence relations in the second phase. If such relations did not develop in the first phase, they did not do so in the second phase. In Phase 3, relations between stimuli across the two previous phases (e.g., B1F1, B2F2, B1G1, B2H2, C1F1, etc.) were investigated. The 4 subjects whose performances showed the development of these relations were taught to select one stimulus from each class (E1 and E2) in response to a verbal label (I1 and I2) and then were tested to see if the verbal label controlled responding to the remaining members of the class (e.g., I1A1, I2A2, I1B1, I2B2, etc.). For 3 subjects, this generalized control occurred; for the 4th, generalization occurred only after verbal training with a second pair of visual stimuli (F1 and F2). In retests several months later, these auditory visual relations were found to be intact or, if not, were recovered without direct training. PMID- 3346623 TI - Oral vaccination. Identification of classes of proteins that provoke an immune response upon oral feeding. AB - Oral immunization of an animal is generally hard to achieve unless large quantities of antigen are administered. In this study a number of antigens were tested for their ability to elicit a systemic immune response upon oral administration. It was found that bacterial pili, LTB, lectins, and a viral hemagglutinin were all able to elicit significant antibody titers upon oral feeding. The immune response thus generated to LTB and K99 pili could be completely abolished by cofeeding a number of sugars that have close structural homology to the terminal sugars of the GM1 and GM2 gangliosides to which these molecules are known to bind. All of the proteins that were active in oral immunization are known to possess "lectin or lectin-like" binding activities. It is therefore proposed that these molecules are able to bind to glycolipids and glycoproteins on the intestinal mucosa and to stimulate these cells to transport the proteins into the systemic circulation, thereby eliciting a systemic immune response. Molecules that did not possess this binding activity were unable to elicit significant responses at the doses tested. PMID- 3346624 TI - Peptides bound to proteosomes via hydrophobic feet become highly immunogenic without adjuvants. AB - Addition of either a lauroyl or a pentapeptide (FLLAV) hydrophobic foot to the NH2 terminus of a small, synthetic peptide allowed the peptide to hydrophobically complex to meningococcal outer membrane protein proteosomes by simple dialysis. Both conventional and LPS-hyporesponsive mice immunized with these complexes without any adjuvants developed high-titered and persistent anti-peptide IgG. Since proteosomes have been safely given to many people and since important antigenic determinants are generally hydrophilic, this system should be widely applicable to the development of peptide vaccines for human use. PMID- 3346626 TI - Selective acceptance of MHC class I-deficient tumor grafts in the brain. AB - H-2-deficient (H-2-) tumor variants were accepted equally well compared with H-2+ wild-type cells in the brain of syngeneic mice, while the H-2- cells were selectively eliminated when inoculated extracranially. This indicates a specific absence or suppression of the defense against MHC class I-deficient cells in the brain, suggested to be mediated by NK cells. In contrast, T cell-mediated immune reactions could clearly be detected in the brain under the same experimental conditions. This was shown in control experiments where H-2+ tumor cells were rejected from the brain of preimmunized or allogeneic mice. The present findings may be important for the understanding of neurotropic virus infections, immunology and immunotherapy of brain tumors, as well as for the growing interest in tissue grafting within the central nervous system. PMID- 3346627 TI - Standards for primary care. PMID- 3346625 TI - Molecular cloning of the major surface antigen of leishmania. AB - The gene encoding gp63, the major surface glycoprotein of Leishmania promastigotes, was isolated from Leishmania major using a synthetic oligonucleotide probe based on the NH2-terminal protein sequence of purified gp63. DNA sequence analysis and the translated amino acid sequence indicate that gp63 is synthesized as precursor molecule having both an NH2-terminal preregion (signal peptide) and an adjacent proregion. This structure is consistent with the protease activity of gp63 since many other proteases are synthesized as precursor forms requiring processing for enzymatic activity. Hybridization studies demonstrated that there are multiple copies of the gp63 gene in the genome of L. major and other Leishmania species. The conservation of the coding sequence of gp63 amongst diverse species of Leishmania provides further support for the importance of gp63 during the life cycle of Leishmania. PMID- 3346628 TI - Somatization disorder. PMID- 3346629 TI - Accidental hypothermia in the elderly. PMID- 3346630 TI - Management of elevated serum cholesterol in a university-based family practice. AB - Hypercholesterolemia is a well-known risk factor of coronary heart disease. This study was designed to determine whether a group of family physicians in an academic medical center followed recent recommendations in the recognition and treatment of young patients with elevated cholesterol levels. Patient charts were reviewed retrospectively in 94.1 percent of the 1,129 patients aged between 30 and 39 years seen in the University of California at Los Angeles (UCLA) Family Health Center over a one-year period. Only 346, or 32.6 percent, of the charts reviewed contained the patient's cholesterol values. Ninety-nine patients had serum cholesterol levels greater than the recommended treatment level of 5.70 mmol/L (220 mg/dL). Of patients with elevated cholesterol levels, only 34.1 percent were treated. There was no difference in the treatment rates of faculty members' patients as compared with residents' patients. The incidence of treatment increased linearly with respect to rising cholesterol values. This study identified the relative infrequency with which cholesterol levels appear in the charts of patients aged 30 to 39 years. It also illustrated that significantly more physician effort is required to meet suggested treatment guidelines for patients with elevated cholesterol levels. The cholesterol "normal ranges" that are reported on laboratory result sheets, which are not age specific, may be misleading, and consequently affect patient care. PMID- 3346631 TI - The medical communication of deaf patients. AB - As language is such a fundamental tool in the determination of a diagnosis and in patient education, non-English-speaking patients and deaf patients often suffer from inferior medical care. Deaf adults and adults studying English as a second language (third- to fifth-grade English-comprehension level) were compared. Participants completed a survey and a test of commonly used medical vocabulary. The two populations did not differ significantly in education level or in vocabulary test scores. Deaf patients were often less able to speak to their physician in their customary language (sign language); as a result, they perceive greater difficulties in expressing themselves to their physicians and reexplain themselves less frequently in response to misunderstandings. It is clear that deaf patients should be recognized as a subset of non-English-speaking patients who are at increased risk for poor physician-patient communication. PMID- 3346632 TI - Alcoholics remaining anonymous: resident diagnosis of alcoholism in a family practice center. AB - Family practice residents rarely detect more than one half of the alcoholic patients they see. This study examines detection rates in terms of the patient's presenting complaint, the clinical encounter, and the resident's attitudes. Over four months 218 patients of the family practice center of a large community hospital completed a survey that included the Short Michigan Alcoholism Screening Test (SMAST). Chart audits of each patient's visit assessed each resident's behavior in recording questions about the patient's use of alcohol. After the first four months, each resident completed a survey of his or her experiences and attitudes concerning alcoholism. Using the SMAST scores and chart audits, 25 of the 218 patients were identified as alcoholic. The residents detected only 12 of the 25 alcoholics. Of 51 patients who presented for physical examinations, the residents recorded asking only 28 about their drinking; of 157 patients who presented for more limited visits, the residents recorded asking only six about their drinking. Residents rated the alcoholic patient as less motivated, more dangerous, less hopeful, and much sicker than the average person. First-year residents rated alcoholics much more negatively than did upper-level residents. The SMAST again proved to be much more effective than clinical interviews in detecting alcoholism in patients. PMID- 3346633 TI - Screening for psychosocial problems in primary care. AB - Evaluating and understanding the physical, emotional, and social condition of a patient is an important component of primary care. Time constraints, however, often make it difficult for the physician to explore these areas in detail with every patient. One approach that can be helpful is the use of a simple questionnaire that can be completed by the patient in advance of seeing the physician. The use of one questionnaire, the Multifactor Health Inventory (MHI), in filling the need for such an instrument is detailed. The MHI helps the physician screen for psychophysiologic, psychiatric, attitudinal, and substance abuse problems. It also provides direction for productive follow-up interviewing. Research has shown that many patients with psychosocial problems are not identified by the physician. A questionnaire can help increase physician awareness of these patients and their problems. PMID- 3346635 TI - Diagnosis of alcoholism. PMID- 3346634 TI - Follow-up study of an urban family medicine home visit program. AB - A home visit program was established by a large urban family practice in an academic setting. At the program's inception, 198 patients were randomly assigned to either an experimental group, to be eligible for home visits, or a control group, to continue receiving only office-based care. Two years after this randomization, follow-up data were obtained on 194 of the 198 subjects to assess the program's effectiveness. Fifty-one of the subjects had died. There were an increased number of deaths in the experimental group (30 percent) compared with the control group (21 percent), although this difference was not statistically significant. No statistically significant differences were found between the remaining 143 experimental and control group patients in function or well-being. Patients in the experimental group had a significantly higher number of hospitalizations, although there was no difference in the number of days spent in the hospital. Although methodologic considerations limit the ability to draw policy conclusions from this follow-up study, this home visit program did not have a measurable sustained impact on health outcomes or utilization of health services. PMID- 3346636 TI - Parapertussis infection in a neonate. PMID- 3346637 TI - Recurrent classical sacculation of the pregnant uterus. PMID- 3346638 TI - Teaching central line placement and other options for intravenous access. PMID- 3346639 TI - A new perspective. PMID- 3346640 TI - Medical practice without liability insurance: is it rational and responsible? PMID- 3346642 TI - PLI: the overriding issue. PMID- 3346641 TI - Have you advised your smoking patients to quit? PMID- 3346643 TI - Focus on AIDS in Florida. PMID- 3346644 TI - Report on an outbreak of lymphogranuloma venereum in central Florida. PMID- 3346645 TI - AMA interim meeting: a myriad of issues, a single voice. PMID- 3346646 TI - ECG of the month. Atrial fibrillation with advanced AV block. PMID- 3346647 TI - Microsurgery 1987: the LSU experience. PMID- 3346648 TI - Sonographic evaluation of acute bacterial meningitis. PMID- 3346649 TI - Preliminary studies of clonidine in psychotic patients. AB - Twelve psychotic patients received a mean dose of 3.3 mg/day of clonidine. In four clonidine was the only treatment and in the remaining eight clonidine was superadded to a neuroleptic regimen after symptomatology was stable. Clonidine caused reduction of scores for both productive psychotic symptoms and anxiety. Negative symptoms were unaffected. These findings are discussed with respect to the small magnitude of the effects, questions as to specificity of the effects and methodologic limitations of this pilot study. PMID- 3346650 TI - Monoamine neurotransmitters in the evolution of infarction in ischemic striatum: morphologic correlation. AB - Evolution of infarction following cerebral ischemia is a delayed process, with spongiform degeneration of the neuropil occurring 6 to 8 hours after onset of ischemia. The brains of gerbils with stroke following unilateral carotid artery ligation were examined for catecholamine-derived fluorescence (CADF) by the Falck Hillarp technique to study the relationship of catecholamine (CA) metabolism with damage to the neuropil. CADF could still be identified in the striatum for up to 16 hours after stroke and there appeared to be spongiform degeneration of the neuropil in relation to accumulations of CADF at 7 and 16 hours after stroke. Pretreatment of gerbils with a-methyl-p-tyrosine 400 mg/kg 6 hours prior to carotid ligation depleted the striatum of CADF until 16 hours after stroke and appeared to reduce the spongiform degeneration of the neuropil, though it did not affect ischemic degeneration of neuronal cell bodies. The continued presence of CADF in the striatum for up to 16 hours after stroke supports the previously reported findings that CA nerve terminals are still functional for 8 hours after stroke and that CA metabolism continues even though levels of CA are reduced immediately after onset of ischemia due to carotid artery ligation. PMID- 3346651 TI - Single treatments with the antidepressant oxaprotiline and its (+) and (-) enantiomers increase behavioural responses to dopaminergic stimulation in the rat. AB - The effects of single doses of oxaprotiline and its (+)- and (-)-enantiomers (CGP 12 104 A and CGP 12 103 A, provisional generic name levoprotiline) on apomorphine and amphetamine-induced stereotypies and amphetamine-induced hyperthermia were investigated in the rat. All 3 compounds enhanced and prolonged stereotyped responses to apomorphine and amphetamine at single doses of 10-30 mg/kg i.p. The most active appeared to be the (-)-enantiomer levoprotiline which is devoid of NA uptake-inhibiting properties. Neither compound, however, potentiated amphetamine induced hyperthermia, suggesting that enhanced behavioural effects are not due to the interference with metabolic degradation of amphetamine. The mechanism of the observed effect remains obscure, but in view of the reported clinical antidepressant action of levoprotiline these findings are interesting. PMID- 3346652 TI - Effect of auditory deafferentation on the synaptic connectivity of a pair of identified interneurons in adult field crickets. AB - In adult crickets, Teleogryllus oceanicus, unilateral auditory deafferentation causes the medial dendrites of an afferent-deprived, identified auditory interneuron (Int-1) in the prothoracic ganglion to sprout and form new functional connections in the contralateral auditory neuropil. The establishment of these new functional connections by the deafferented Int-1, however, does not appear to affect the physiological responses of Int-1's homolog on the intact side of the prothoracic ganglion which also innervates this auditory neuropil. Thus it appears that the sprouting dendrites of the deafferented Int-1 are not functionally competing with those of the intact Int-1 for synaptic connections in the remaining auditory neuropil following unilateral deafferentation in adult crickets. Moreover, we demonstrate that auditory function is restored to the afferent-deprived Int-1 within 4-6 days following deafferentation, when few branches of Int-1's medial dendrites can be seen to have sprouted. The strength of the physiological responses and extent of dendritic sprouting in the deafferented Int-1 progressively increase with time following deafferentation. By 28 days following deafferentation, most of the normal physiological responses of Int-1 to auditory stimuli have been restored in the deafferented Int-1, and the medial dendrites of the deafferented Int-1 have clearly sprouted and grown across into the contralateral auditory afferent field. The strength of the physiological responses of the deafferented Int-1 to auditory stimuli and extent of dendritic sprouting in the deafferented Int-1 are greater in crickets deafferented as juveniles than as adults. Thus, neuronal plasticity persists in Int-1 following sensory deprivation from the earliest juvenile stages through adulthood. PMID- 3346653 TI - Evidence for an absence of estrogen-concentration by CCK-immunoreactive neurons in the hypothalamus of the female rat. AB - It is becoming increasingly clear that the neuropeptide cholecystokinin (CCK), widely distributed in the rat hypothalamus and limbic system, is subject to both organizational and activational influences of steroid hormones. Sex differences in numbers of CCK-immunoreactive elements have been demonstrated in sexually dimorphic structures such as the bed nucleus of the stria terminalis, medial preoptic nucleus, and ventromedial nucleus of the hypothalamus. Steroid activation of CCK has been indicated by findings that hypothalamic CCK levels and binding capacity vary over the estrous cycle. These studies, in combination with evidence of CCK mediation of sexually differentiated functions, prompted us to test for estrogen concentration among CCK-containing cells of the female rat hypothalamus by combining the techniques of immunohistochemistry and autoradiography. A method employing 2-week ovariectomies and perfusion fixation with 4% paraformaldehyde was compatible with the localization of both estrogen accumulating and CCK-immunoreactive cell bodies. The maintenance of numbers of CCK-positive cells after gonadectomy suggested that expression of this peptide may not be directly regulated by ovarian steroids in female rats. This suggestion was substantiated by the finding that, with rare exceptions, CCK-immunoreactive cells did not concentrate estrogen in tissues collected from the anterior posterior extent of the bed nucleus of the stria terminalis, medial preoptic nucleus, anterior hypothalamic area, and paraventricular nucleus. PMID- 3346654 TI - Multiple transmitter neurons in Tritonia. I. Biochemical studies. AB - The buccal ganglia of the marine mollusc Tritonia control a variety of movements associated with feeding, including gut motility. The buccal ganglia and gut contain a class of peptides termed small cardioactive peptides (SCPs). Cobalt backfilling of the nerve which innervates the gut stains several buccal neurons including two pairs of reidentifiable cells, B11 and B12. Both appear white under epiillumination, a characteristic of peptidergic neurons in gastropods. Enzymatic and biochemical analyses of extracts from microdissected B11 cell bodies demonstrate that this neuron contains two species of SCPs. Labeling in organ culture followed by dissection and extraction of cell bodies indicates that these peptides were synthesized in B11. One of these peptides appears to be identical to SCPB, one of two SCPs that have been sequenced. The other SCP present in these neurons is novel. Less extensive analyses of extracts of B12 somata suggest that it also contains the same SCPs. In addition to the peptides, B11 also contains large quantities of acetylcholine (ACh) as determined by a radioenzymatic assay of cell body extracts. B12 does not contain measureable ACh. The concentration of the two peptides and ACh in the B11 cytoplasm is approximately 1 mM. Neuron B11 appears to be an appropriate model system for studying the biochemical and physiological properties of multiple transmitter neurons. PMID- 3346655 TI - Multiple transmitter neurons in Tritonia. II. Control of gut motility. AB - Two large multiple transmitter neurons are located in each buccal ganglion of Tritonia. One of these neurons (B11) contains large quantities of two neuropeptides and acetylcholine (ACh), whereas the other neuron (B12) appears to contain the same two peptides but no ACh. One of the peptides present in these neurons has recently been sequenced and is termed small cardioactive peptide B (SCPB). Both neurons regulate the motility of the gut. Stimulation of B11 produces a posteriorly directed peristalsis after a short latency. This gut movement may normally accompany swallowing. B11 stimulation also produces an increase in the rate of endogenous contractile activity that is similar to that produced by superfusion of the gut with low concentrations (10(-8) M) of SCPB. Stimulation of B12 produces a vigorous longitudinal contraction of the gut, initiated in the posterior part of the gut and not peristaltic in nature. This movement appears incompatible with swallowing behavior and may be involved in regurgitation. PMID- 3346656 TI - Multiple transmitter neurons in Tritonia. III. Modulation of central pattern generator controlling feeding. AB - Feeding behavior in the gastropod mollusc Tritonia diomedea is controlled by a central pattern generator (CPG) in the buccal ganglia. The medially located, large dorsal white cells (B11) have been shown to contain two small cardioactive peptides (SCPs). A smaller nearby neuron (B12) also appears to contain the SCPs. B11's have also been shown to contain acetylcholine (ACh), whereas B12's do not. We have shown earlier that intracellular stimulation of B11's drives contractions of the foregut. Here we show that intracellular electrical stimulation of B11's also elicits excitation of neurons B5 and stimulates the patterned motor output of the CPG. We showed earlier that B12's also stimulate contractions in the foregut, but they are in the opposite direction from those elicited by B11. We show here that electrical stimulation of B12's inhibits the output of the CPG. We showed earlier that superfusion of the isolated gut with SCPB enhances peristalsis, and here we report that superfusion of the buccal ganglion with SCPB elicits enhanced coordinated motor output from the CPG. The peptide has two effects on the bursting output of motor neurons. It produces an increase in (1) the rate of bursting and (2) the spike frequency during each burst. On the other hand, we reported earlier that ACh applied directly to isolated foregut inhibits ongoing peristalsis. Here we demonstrate that ACh superfusion of the buccal ganglion also inhibits the CPG output. Our evidence supports the view that in addition to stimulating foregut contractility, B11's modulate the output of the swallowing CPG by releasing a peptide from central terminals. We suggest roles for B11, B12, the SCPs, and ACh in controlling both central and peripheral aspects of feeding behavior. PMID- 3346657 TI - The molluscan neuropeptide, SCPB, increases the responsiveness of the feeding motor program of Limax maximus. AB - Small cardioactive peptide B (SCPB) has an excitatory effect on both buccal neurons and musculature in numerous molluscan species. The present study reports the effects of SCPB on the activity of specified buccal neurons and the expression of the feeding motor program of the terrestrial slug, Limax maximus. Superfusion of an isolated CNS preparation with 10(-6)M SCPB results in a 3-4 fold increase in the burst frequency of the fast salivary burster neuron (FSB), while having no effect on the activity of another endogenous burster, the bilateral salivary neuron (BSN). The response of the FSB to SCPB is dose dependent, with a threshold concentration of 2 X 10(-8)M. The response of the FSB to SCPB showed no indication of desensitization, even after long-term exposure (20 min). The feeding motor program (FMP) in Limax is a discrete pattern of cyclical motor activity that can be initiated by lip nerve stimulation. In the presence of SCPB a previously subthreshold stimulus can initiate the full FMP. The pattern of the FMP, once initiated, appears unaffected by SCPB. Thus it is the responsiveness of the initiation process that is enhanced by SCPB. Histochemical studies revealed a number of buccal neuron somata and fibers that stain for SCPB-like immunoreactive material (SLIM). PMID- 3346658 TI - 13C NMR studies of D- and L-phenylalanine binding to cobalt(II) carboxypeptidase A. AB - 13C NMR T1 and T2 measurements have been performed on cobalt(II) substituted carboxypeptidase A in the presence of carboxylate-13C-enriched L- and D phenylalanine. Upon binding to the cobalt enzyme, the longitudinal and transverse relaxation rates T1p-1 and T2p-1 of these inhibitors are enhanced significantly compared to the zinc enzyme, allowing both determination of an affinity constant for inhibitor binding, K, and calculation of the metal-13C carboxylate distances. The L-and D- Phe concentration dependence of T2p-1 yields affinity constants of 290 +/- 60M-1 and 670 +/- 90M-1. The distance measurements calculated for Co-13C from T1p-1 are 0.39 +/- 0.04 and 0.42 +/- 0.04 nm for L-Phe and D-Phe. Both values are too great for direct coordination of their carboxylate groups to the metal atom. Upon formation of their respective ternary enzyme.Phe.N3- complexes, the distances are essentially unaltered. In conjunction with electronic absorption studies on these complexes it can be concluded that N3-, but not the amino acid carboxylate, is bound to the metal. PMID- 3346659 TI - 13C NMR studies of carboxylate inhibitor binding to cobalt(II) carboxypeptidase A. AB - Both 13C NMR and electronic absorption spectral studies on cobalt(II) carboxypeptidase A in the presence of acetate and phenylacetate provide evidence for two binding sites for each of these agents. The transverse relaxation rate T2 1 for the 13C-enriched carboxyl groups of the inhibitors is significantly increased when bound to the paramagnetic cobalt carboxypeptidase as compared to the diamagnetic zinc enzyme. The acetate concentration dependence of T2p-1 shows two inflections indicative of sequential binding of two inhibitor molecules. The cobalt-13C distances, calculated by means of the Solomon equation, indicate that the second acetate molecule binds directly to the metal ion while the first acetate molecule binds to a protein group at a distance 0.5-0.8 nm for the metal ion, consistent with it binding to one or more of the arginyl residues (Arg-145, Arg-127, or Arg-71). In the case of phenylacetate, perturbation of the cobalt electronic absorption spectrum shows that binding occurs stepwise. 13C NMR distance measurements indicate that one of the two phenylacetates is bound to the metal in the EI2 complex. These binding sites may correspond to those identified previously by kinetic means (one of which is competitive, the other noncompetitive) with peptide binding. The studies further indicate that it should be possible to map the protein interactions of the carbonyl groups of both substrate and noncompetitive inhibitors during catalysis by means of 13C NMR studies with suitably labeled substrates and inhibitors. PMID- 3346660 TI - Effect of metal ions on the fluorescence of leucine aminopeptidase and its dansyl peptide substrates. AB - The effect of Cu(II), Ni(II), Zn(II), Mg(II), and Mn(II) on the fluorescence of porcine kidney cytosol leucine aminopeptidase and three of its dansyl(Dns) peptide substrates, Leu-Gly-NHNH-Dns, Leu-Gly-NH(CH2)2NH-Dns, and Leu-Gly NH(CH2)6NH-Dns, has been investigated. These five metal ions were chosen for study because each binds to the regulatory metal binding site of leucine aminopeptidase. Since the binding is relatively weak, kinetic studies of the different metalloderivatives of the enzyme are normally carried out in the presence of large molar excesses of these metal ions that can potentially affect both the enzyme and substrate. The fluorescence of all of the dansyl-peptides, as well as several other dansyl species, is quenched by Ni(II) and Cu(II), but not by Mg(II), Mn(II), or Zn(II). The absorption spectra of these dansyl substrates are also perturbed by Ni(II) and Cu(II). The rate at which maximal quenching for some dansyl species is attained after mixing with Ni(II) and Cu(II) is slow and the quenching is reversed on addition of EDTA. These results indicate that the quenching is the result of complex formation between the fluorophores and these metal ions. The association constants for the metal complexes have been determined from Stern-Volmer plots. In addition to complex formation, Ni(II) and Cu(II) cause the degradation of Leu-Gly-NHNH-Dns through a two step mechanism involving loss of dansic acid. Ni(II) and Cu(II) also partially quench the fluorescence of leucine aminopeptidase through contact with its surface accessible Trp residues. These observations indicate that care must be taken in stopped flow fluorescence studies of reactions between this enzyme and its dansyl substrates to avoid adverse effects brought about by Ni(II) and Cu(II). PMID- 3346661 TI - Interactions of porphyrins with purified DNA and more highly organized structures. AB - Studies of the solution properties of gold(III)tetrakis(4-N-methylpyridyl) porphine and its DNA binding characteristics have been conducted utilizing uv/vis absorption spectroscopy, circular dichroism (CD), Mossbauer spectroscopy, and temperature-jump relaxation techniques. These studies indicate that over the concentration range considered this water soluble gold(III) porphyrin does not aggregate, binds axial ligands only weakly with a preference for soft Lewis bases, and is capable of intercalation into nucleic acids of appropriate base pair content. The interaction of this and several other porphyrins with the synthetic polynucleotide poly(dA-dC).poly(dT-dG) has been studied. Spectroscopic signatures for intercalation were found for those derivatives not having axial ligands. Intercalation into chromatin in vitro can also occur with those porphyrins and metalloporphyrins which do not have axial ligands. Finally, studies utilizing microinjection techniques indicate that once within the cell, tetrakis(4-N-methylpyridyl)porphine tends to localize in the nucleus. PMID- 3346662 TI - NMR investigation of the copper(II)-carnosine complex in water solution. AB - The predominant species in water solution of excess carnosine and Cu2+ ions was characterized by measuring 13C and 1H spin-lattice and spin-spin relaxation rates. Four peptide molecules were calculated to be coordinated to the metal through the imidazole nitrogen. Evaluation of ion-proton distances demonstrated that metal complexation does not involve severe changes in conformation of the peptide. PMID- 3346663 TI - Structural and chemical characterization of gallstones resistant to dissolution therapy. AB - X-ray diffraction, i.r. spectroscopic, and chemical analyses have been carried out on radiolucent gallstones resistant to dissolution therapy. Cholesterol represents the main component of all the examined stones, while the ratio between the amounts of pigmented material and calcium carbonate is about 1 in the inner and outer layers of the stones and 3 in the medial layer. Calcium carbonate is present in two distinct crystalline forms: vaterite, which is the main inorganic crystalline phase, and calcite. The cell parameters of vaterite and calcite are shorter in the inner and outer layers of the stones than in the medial layer. The observed variation of the cell parameters has been related to the substitution of copper to calcium in the carbonate structures, on the basis of the data obtained on vaterite and calcite synthesized in presence of different copper concentrations in solution. The results indicate that the failure of the dissolution therapy can be related to the inhomogeneous distribution in the stones of calcium carbonate and calcium bilirubinate. PMID- 3346664 TI - The preparation and characterization of Cr(III) and Co(III) complexes of GDP and GTP and their interactions with avian phosphoenolpyruvate carboxykinase. AB - The exchange inert coordination complexes, Cr(H2O)4GDP, Cr(H2O)4GTP, Cr(NH3)4GDP, Cr(NH3)4GTP, Co(NH3)4GDP, and Co(NH3)4GTP have been synthesized and characterized. The lambda and delta coordination isomers of Cr(H2O)4GDP, Cr(NH3)4GDP, and the four Cr(H2O)4GTP isomers have been separated by reverse phase HPLC and characterized by their CD spectra. While the isomers of Co(NH3)4GTP have not been successfully separated, 31P NMR spectroscopy reveals the presence of the lambda and delta forms. The complexes, Cr(H2O)4GDP, Co(NH3)4GDP, Cr(H2O)4GTP, and Co(NH3)4GTP, are linear competitive inhibitors of avian phosphoenolpyruvate carboxykinase. The Ki values of 30 microM, 540 microM, 40 microM, and 12 microM, respectively, were determined for these complexes using Mn-IDP as the nucleotide substrate in the phosphoenolpyruvate carboxylation direction or Mn-ITP as nucleotide substrate for the oxalacetate decarboxylation reaction. The lambda and delta isomers of Cr(H2O)4 GDP show little specificity (a twofold maximum difference in Ki) for the enzyme. The isomeric forms of Cr(H2O)4 GTP demonstrate no observed stereoselectivity of interaction with the enzyme. All of the complexes tested, except for Cr(NH3)4GDP and Co(NH3)4GDP, which have larger Ki values, are good substrate analogs for P-enolpyruvate carboxykinase. When the substrate is Mn-GTP, fixed at 0.2 mM at pH 6.0, enzyme activity is stimulated two- to two and a half-fold by Cr(H2O)4GTP. A Dixon plot reveals that the stimulatory effect is saturated at 0.4 mM Cr(H2O)4GTP. The interaction of the enzyme with Cr(H2O)4GTP appears to produce a "memory" effect which is manifest with guanosine nucleotide substrates, but which is not observed with the alternative substrate Mn-ITP. PMID- 3346665 TI - A 119Sn Mossbauer spectroscopic study on the interaction of dimethyltin (IV) derivatives with rat hemoglobin, and of related model systems in aqueous solution. AB - In the context of a study of the molecular basis of the antileukemia (murine) activity of diorganotin (IV) compounds, the interaction with rat hemoglobin (selected as a model protein) of the representative terms dimethyltin dichloride, dimethyltin glycylglycinate (Me2SnGlyGly), and dimethyltin L-cysteinate (Me2Sn Cys) has been investigated by 119Sn Mossbauer spectroscopy. In order to possibly determine the reaction pathway, aqueous model systems in Hepes buffer at pH 7.4 were also considered. The structural characteristics of reactants and products were advanced on the basis of semiempirical calculations of Mossbauer nuclear quadrupole splitting parameters, delta E, by the point-charge model approach. In aqueous Hepes at pH 7.4, evidence was obtained for the formation of the five coordinated species, trigonal bipyramidal type (tbp), Me2Sn(OH)2.Hepes(II), Me2Sn(OH)(GlyGly).Hepes(III), and Me2Sn(OH)Cys(IV) (see Fig. 1). Equatorial groups or atoms would be the Me radicals, as well as OH, N(peptide), and S(thiol), respectively. Hepes would coordinate to tin in axial position through the tertiary amino nitrogen, while cysteine would behave as a bidentate chelating agent, with an axially located amino group. Species (II), (III), and (IV) react with cysteine in aqueous Hepes at pH 7.4, yielding Me2Sn(OH)Cys(IV), as well as Me2SnCys2(V), where tin would be embedded into a tbp structure due to one cysteine probably chelating (equatorial S thiol and axial amino nitrogen), and one monodentate through S thiol. Species (II), (III), and (IV) react analogously with rat hemoglobin, primarily through the S thiol of a cysteine side chain, yielding pellets where the environment of tin could be tetrahedral, such as in Me2Sn(OH)(S thiol), (VI), and tetrahedral (IX) or tbp (V) in Me2Sn(Cys)(S thiol), where Cys would act either as chelating or monodentate. Further reaction of (VI) and (IX) could involve imidazole nitrogen atoms, N het, of histidine side chains, forming tetrahedral Me2Sn(S thiol)(N het), (VIII), or tbp Me2Sn(OH)(S thiol)(N het), (VII), and Me2Sn(Cys)(S thiol)(N het), (V) (see Figs. 1 and 5). PMID- 3346666 TI - Formation of the neurotransmitter glycine from the anticonvulsant milacemide is mediated by brain monoamine oxidase B. AB - Milacemide (2-n-pentylaminoacetamide) is a secondary monoamine that in the brain is converted to glycinamide and glycine. This oxidative reaction was suspected to involve the reaction of monoamine oxidase (MAO). Using mitochondrial preparations from tissues that contain MAO-A and -B (rat brain and liver), MAO-A (human placenta), and MAO-B (human platelet and bovine adrenal chromaffin cell), it has been established that mitochondria containing MAO-B rather than MAO-A oxidize (H2O2 production and glycinamide formation) milacemide. The apparent Km (30-90 microM) for milacemide oxidation by mitochondrial MAO-B preparations is significantly lower than that for milacemide oxidation by mitochondrial MAO-A (approximately 1,300 microM). In vitro MAO-B (l-deprenyl and AGN 1135) rather than MAO-A (clorgyline) selectively inhibited the oxidation of milacemide. These in vitro data are matched by ex vivo experiments where milacemide oxidation was compared to oxidation of serotonin (MAO-A) and beta-phenylethylamine (MAO-B) by brain mitochondria prepared from rats pretreated with clorgyline (0.5-10 mg/kg) and l-deprenyl (0.5-10 mg/kg). Furthermore, in vivo experiment demonstrated that l-deprenyl selectively increased the urinary excretion of [14C]milacemide and the total radioactivity with a concomitant decrease of [14C]glycinamide. Such changes were not observed after clorgyline treatment, but were evident only at doses beyond clorgyline selectivity. The present data therefore demonstrate that milacemide is a substrate for brain MAO-B, and its conversion to glycinamide, further transformed to the inhibitory neurotransmitter, glycine, mediated by this enzyme may contribute to its pharmacological activities. PMID- 3346667 TI - Demonstration and biochemical characterisation of rat brain NADPH-dependent diaphorase. AB - An enzyme responsible for the NADPH-dependent reduction of nitroblue tetrazolium HCl (NBT) has been isolated from rat brain. Although other tetrazolium salts could be utilised, NBT was the preferred substrate, and the enzyme had an absolute requirement for NADPH. An in vitro assay was developed and used to determine the kinetic constants: Km NBT = 17.3 microM; Km NADPH = 1.9 microM, Vmax = 30.8 mumol product produced/min/mg protein. Substrate inhibition by NADPH was observed in some instances. Brain subcellular fractionation indicated highest enzyme activities in the microsomal fraction. Activity was present in all brain regions and in a variety of peripheral tissues. Relative molecular mass determinations of the native enzyme yielded an Mr = 170-180,000. It seems likely that the enzyme activity described in this study relates directly to the histochemical demonstration of brain NADPH-diaphorase-positive neurons. As yet, the natural substrate for the enzyme is unknown. However, the isolation and purification of NADPH-dependent diaphorase may be anticipated to assist in the elucidation of its function in the brain, and in the special characteristics of those neurons that contain the enzyme in abundance. PMID- 3346668 TI - Muscarinic modulation of purine release from electrically stimulated rat cortical slices. AB - The release of 3H-labeled purines at rest and during electrical stimulation was investigated in slices of rat cortex prelabeled with [3H]adenine and perfused with Krebs solution. A linear relationship was found between radioactivity efflux and stimulation frequency from 2.5 to 20 Hz. At frequencies of less than 2.5 Hz, no increase in radioactivity efflux was detected. The amount of tritium released per pulse increased with stimulation frequency up to 10 Hz and declined at 20 Hz. The tritium efflux from the slices at rest and at a stimulation frequency of 10 Hz, analyzed by HPLC with ultraviolet absorbance detection at 254 nm, consisted mostly of adenosine, inosine, and hypoxanthine. The 3H-labeled purine release evoked by 10-Hz stimulation increased with current intensity from 15 to 100 mA/cm2. At 20 mA/cm2, addition of 0.5 microM tetrodotoxin to the superfusing Krebs solution brought about a 98% decrease of 3H-labeled purine release. At higher current strength, the percentage of tetrodotoxin-sensitive-evoked tritium efflux was smaller. At 30 mA/cm2, 86% of the evoked release was tetrodotoxin sensitive. Under these stimulation conditions, tritium efflux showed a 69% decrease when the slices were superfused with calcium-free Krebs solution containing 0.5 mM EGTA. The muscarinic agonist oxotremorine (30 microM) significantly enhanced the 10-Hz-stimulated 3H-labeled purine release. The effect of oxotremorine was partially prevented by tetrodotoxin, was antagonized by atropine (1.5 microM), and was mimicked by addition of physostigmine (3.8 microM) to the superfusion fluid. Atropine alone did not affect the evoked release, and none of the drugs modified the basal tritium efflux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346669 TI - Inhibition of type A monoamine oxidase by methylquinolines and structurally related compounds. AB - A series of methylquinolines (MQ) were found to inhibit markedly type A monoamine oxidase (MAO) in human brain synaptosomal mitochondria. 4-MQ and 6-MQ inhibited type A MAO (MAO-A) competitively and 7- and 8-MQ inhibited MAO-A noncompetitively. Among these four isomers of MQ, 6-MQ was the most potent inhibitor; the Ki value toward MAO-A was 23.4 +/- 1.8 microM, which was smaller than the Km value toward kynuramine, an amine substrate, 46.2 +/- 2.8 microM. On the other hand, MQ were very weak inhibitors of type B MAO (MAO-B) and 8-MQ did not inhibit MAO-B in brain synaptosomal mitochondria. The inhibition of MAO-A proved to be reversible; by dialysis the inhibition of MQ was completely reversible. The affinity of these isomers of MQ toward MAO-A or -B was confirmed further with human liver mitochondria as sources of MAO-A and -B and with human placental mitochondria and rat pheochromocytoma PC12h cell line as sources of MAO A. The relationship of the chemical structure of structurally related quinoline and isoquinoline derivatives to inhibition of the activity of type A or B MAO was examined. PMID- 3346670 TI - Stereoselective nicotine-induced release of dopamine from striatal synaptosomes: concentration dependence and repetitive stimulation. AB - Using a sensitive perfusion system we have studied the nicotine-induced release of [3H]dopamine ([( 3H]DA) from striatal synaptosomes. Nicotine-evoked release was concentration dependent with an EC50 of 3.8 microM. The response to 1 microM nicotine was comparable to that to 16 mM K+; 10 microM veratridine evoked a larger response. All three stimuli were Ca2+ dependent but only the response to veratridine was blocked by tetrodotoxin. Repetitive stimulations by 1 microM (-) nicotine (100 microliters) at 30-min intervals resulted in similar levels of [3H]DA release; higher concentrations of (-)-nicotine resulted in an attenuation of the response particularly following the third stimulation. This may reflect desensitisation or tachyphylaxis of the presynaptic nicotinic receptor. The action of nicotine was markedly stereoselective: a 100-fold higher concentration of (+)-nicotine was necessary to evoke the same level of response as 1 microM (-) nicotine. It is proposed that these presynaptic nicotinic receptors on striatal terminals are equivalent to high-affinity nicotine binding sites described in mammalian brain. PMID- 3346671 TI - [3H]dihydrotetrabenazine, a new in vitro monoaminergic probe for human brain. AB - The monoamine transporter of dopamine (DA), noradrenaline, and 5 hydroxytryptamine synaptic vesicles was assayed in rat and human brain homogenates by in vitro binding of [3H]dihydrotetrabenazine. [3H]Reserpine, a second ligand of the vesicular monoamine transporter, could not be used. [3H]Dihydrotetrabenazine binding in rat brain was stable after 72 h at 22 degrees C postmortem. In major human brain regions, [3H]dihydrotetrabenazine binding was specific and saturable (KD, 2.7 nM). Displacement constants by substrates or inhibitors of vesicular monoamine uptake, and regional distribution in human brain were similar to those found in rodents. The highest densities of binding sites were observed in caudate nucleus, putamen, and accumbens nucleus. In caudate nucleus and in putamen from normal human subjects, [3H]dihydrotetrabenazine binding and homovanillic acid concentration were significantly or nearly significantly correlated. A weaker correlation was found between [3H]dihydrotetrabenazine binding and DA, in association with a higher variability of DA. [3H]Dihydrotetrabenazine binding in caudate nucleus and in putamen decreased significantly with age, unlike DA and homovanillic acid concentrations. The results establish [3H]dihydrotetrabenazine as a presynaptic monoaminergic ligand of interest for studies on postmortem human brain. PMID- 3346672 TI - Monoamine oxidase-inhibiting properties of SR 95191, a new pyridazine derivative, in the rat: evidence for selective and reversible inhibition of monoamine oxidase type A in vivo but not in vitro. AB - In rodents, SR 95191 [3-(2-morpholinoethylamino)-4-cyano-6-phenylpyridazine] has been shown to be active in animal models of depression. The profile of activity of SR 95191 suggests that the compound is a selective and short-acting type A monoamine oxidase (MAO) inhibitor (MAOI) in vivo. In the present study, the interaction of SR 95191 with MAO-A and MAO-B activity was further examined in vivo and in vitro. In brain, liver, and duodenum of pretreated rats, SR 95191 selectively inhibited MAO-A (ED50 = 3-5 mg/kg, p.o.), whereas MAO-B was only weakly inhibited for doses as high as 300 mg/kg, p.o. In vivo, SR 95191 (1-100 mg/kg, p.o.) antagonized, in a dose-dependent fashion, the irreversible inhibition of brain and liver MAO-A induced by phenelzine. Finally, dopamine and 5-hydroxytryptamine depleted from their striatal stores by tetrabenazine were able to displace SR 95191 from the active site of MAO-A. However, ex vivo, kinetic studies showed that the inhibitory effect of SR 95191 (1-10 mg/kg) towards MAO-A was noncompetitive and was unchanged after dilution or dialysis. In vitro, the inhibition of brain MAO-A, but not MAO-B, by SR 95191 was time dependent, with a 19-fold decrease in the IC50 values being observed over a 30 min incubation period (140 to 7.5 microM). At this time, the SR 95191-induced inhibition of MAO-A was not removed by repeated washings. When the reaction was started by adding the homogenate without prior preincubation with SR 95191, the inhibition of brain MAO-A was fully competitive (Ki = 68 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346673 TI - Protein kinase C in primary astrocyte cultures: cytoplasmic localization and translocation by a phorbol ester. AB - The distribution of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) in supernatant and particulate fractions of primary cultures of rat astrocytes and its translocation by a phorbol ester were studied. We observed that 91% of protein kinase C activity in astrocytes was in the supernatant fraction, as measured by lysine-rich histone phosphorylation assay. Attempts to uncover latent activity in the particulate fraction were unsuccessful. Approximately 75% of the supernatant protein kinase C activity could be translocated to the particulate fraction by prior treatment (30-60 min) of the cultures with 100 nM 12-O-tetradecanoyl-phorbol 13-acetate (TPA), but not with 4 alpha-phorbol, an inactive phorbol ester. Investigation of endogenous substrates for protein kinase C showed that TPA treatment brought about an increase in phosphorylation in membrane proteins and a decrease in phosphorylation of supernatant proteins. These findings indicate that the distribution of protein kinase C in astrocytes differs substantially from that in whole brain tissue, where approximately two-thirds of the protein kinase C activity is associated with the particulate fraction. Because protein kinase C is concentrated in the cytosol of astrocytes and most of this activity can be translocated to membranes, astrocytes may be particularly well-suited to respond to signals that activate phosphoinositide-linked receptors in brain. PMID- 3346674 TI - Hydrolysis of the brain dipeptide N-acetyl-L-aspartyl-L-glutamate: subcellular and regional distribution, ontogeny, and the effect of lesions on N-acetylated alpha-linked acidic dipeptidase activity. AB - N-Acetylated-alpha-linked acidic dipeptidase (NAALADase) is a Cl- dependent, membrane bound, metallopeptidase that cleaves the endogenous neuropeptide N acetyl-L-aspartyl-L-glutamate (NAAG) in vitro. To examine the pattern of NAALADase expression in the CNS, subcellular, regional, and developmental studies were conducted. Subcellular fractionation of lysed synaptosomal membranes revealed a substantial enrichment of the peptidase in synaptic plasma membranes as compared to mitochondrial or myelin subfractions. Regional studies reveal an apparent restriction of peptidase activity to kidney and brain. A threefold variation in specific activity was observed among brain regions, with highest specific activity in the cerebellum and lowest in telencephalic structures, a pattern that does not, in general, correlate with NAAG levels. Ontogenetic studies demonstrate a region-dependent, postnatal pattern of expression of NAALADase activity, with adult levels attained earliest in brainstem, as was previously reported for NAAG. Postnatal NAALADase expression would not appear to support a role for the peptidase in constitutive protein processing, but rather suggests that NAALADase may play a role in synaptic peptide degradation. Glutamate (Glu) excised from NAAG by NAALADase could be transported efficiently by uptake processes. Lesion studies, however, do not support a close structural association between NAALADase activity and the corticostriatal sodium-dependent, high-affinity, Glu uptake system. Similar to in vitro data documenting the route of NAAG degradation by NAALADase, after intrastriatal injection, NAAG was rapidly cleaved to two major products, N-acetyl-aspartate and Glu, with a t1/2 of approximately 10 min. Thus, the route of in vivo catabolism of NAAG parallels results from studies on NAALADase activity in vitro. These results are consistent with a role of NAALADase in the synaptic processing of NAAG. However, certain discrepancies in the regional and ontogenetic profiles of NAAG and NAALADase suggest that this relationship is not an exclusive one and may reflect a role for NAALADase on additional N-acetylated acidic peptides in vivo. PMID- 3346676 TI - Evidence that tobacco smoking increases the density of (-)-[3H]nicotine binding sites in human brain. AB - In a postmortem study of nicotinic receptors in human brain, cigarette smoking was found to be associated with increased (-)-[3H]nicotine binding to membranes prepared from gyrus rectus (Brodmann area 11) (p less than 0.001), hippocampal neocortex (Brodmann area 27), cerebellar cortex (p less than 0.01), hippocampal formation (Ammon's horn + subiculum), and the median raphe nuclei of the midbrain (p less than 0.05) but not the medulla oblongata. Analysis of the binding data suggested that the increased binding reflected an increase in the density of the receptors rather than a change in their affinity for (-)-nicotine. The effects of smoking were not influenced significantly by either the sex or age of the subject. It is concluded that smoking evokes an increase in high-affinity nicotine binding similar to that observed previously in animals treated chronically with nicotine and that the effect of smoking on these sites is probably caused by the nicotine present in the tobacco smoke. PMID- 3346675 TI - Blood-brain barrier transport of 1-aminocyclohexanecarboxylic acid, a nonmetabolizable amino acid for in vivo studies of brain transport. AB - Regional transport of 1-aminocyclohexanecarboxylic acid (ACHC), a nonmetabolizable amino acid, across the blood-brain barrier was studied in pentobarbital-anesthetized rats using an in situ brain perfusion technique. The concentration dependence of influx was best described by a model with a saturable and a nonsaturable component. Best-fit values for the kinetic constants of the frontal cortex equaled 9.7 X 10(-4) mumol/s/g for Vmax, 0.054 mumol/ml for Km, and 1.0 X 10(-4) ml/s/g for KD in the absence of competing amino acids. Saturable influx could be reduced by greater than 85% by either L-phenylalanine or 2 aminobicyclo[2.2.1]heptane-2-carboxylic acid, consistent with transport by the cerebrovascular neutral amino acid transport system. The transport Km for ACHC was one-fifth that for the more commonly used homologue, 1 aminocyclopentanecarboxylic acid, and was similar to values for several natural amino acids, such as L-methionine, L-isoleucine, and L-tyrosine. The results indicate that ACHC may be a useful probe for in vivo studies of amino acid transport into brain. PMID- 3346677 TI - Effects of prolonged depolarization on the nicotinic acetylcholine receptors of PC12 cells. AB - To determine whether prolonged depolarization and/or changes in intracellular Ca2+ concentrations stimulate adaptive responses of neuronal nicotinic acetylcholine receptors, PC12 pheochromocytoma cells were grown in medium containing various concentrations of K+. Nicotinic receptor function was determined as carbachol-stimulated uptake of 86Rb+. Cells were exposed to 50 mM K+ for up to 4 days and then allowed to repolarize for 60 min. Under these conditions, no changes in basal or carbachol-stimulated uptake of 86Rb+ were observed. Furthermore, neither the time course of carbachol-stimulated uptake or the carbachol concentration dependence of 86Rb+ uptake was altered. Finally, concurrent depolarization did not affect the functional down-regulation produced by chronic exposure of the cells to carbachol. Thus, neuronal nicotinic acetylcholine receptors on PC12 cells do not appear to be regulated by depolarization or prolonged elevation of the intracellular Ca2+ level. PMID- 3346678 TI - Activation of glucocorticoid-type II receptor complexes in brain cytosol leads to an increase in surface hydrophobicity as determined by hydrophobic interaction chromatography. AB - Hydrophobic interaction chromatography has been used to demonstrate an increase in the surface hydrophobicity of [3H]triamcinolone acetonide ([3H]TA)-labeled type II receptors in mouse brain cytosol following transformation of these receptor complexes to the activated DNA-binding form. After removing unbound [3H]TA and molybdate (which prevents activation) by gel filtration, [3H]TA-type II receptors were activated by incubation at 22 degrees C for 20 min. Gel filtration was then used to remove newly dissociated steroid and to readjust the molybdate and/or KCl concentration. Unactivated and activated receptors were then added to propyl, butyl, pentyl, hexyl, octyl, decyl, and dodecyl alkyl agarose, phenyl agarose, or unmodified agarose columns equilibrated and eluted with buffers of various molybdate and KCl concentrations and/or other additions, including glycerol, ethylene glycol, and urea. Under high-salt conditions, activated receptors were retained longer than unactivated receptors run on butyl, pentyl, hexyl, and phenyl agaroses. With the longer alkyl chain columns, essentially none of the [3H]TA was eluted in association with receptor macromolecules. Removal of the remaining steroid required receptor denaturation with urea. Under low-salt conditions, both receptor forms were retained more avidly on all alkyl agarose columns; however, on phenyl agarose only activated receptors displayed this increased retention. Further studies revealed that optimal separation and subsequent recovery of unactivated and activated [3H]TA type II receptor complexes were achieved on pentyl agarose columns equilibrated and eluted with buffers containing 50 mM molybdate and 600-1,200 mM KCl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346680 TI - Reevaluation of taurine levels and distribution of cysteic acid decarboxylase in developing human fetal brain regions. AB - The possibilities of interference by glycerophosphoryl ethanolamine (GPE) in the estimation of taurine levels in cerebral cortex, midbrain, cerebellum, medullapons, and spinal cord of developing human fetal brain regions were eliminated by hydrolyzing tissue extracts with 6 M HCl. Cysteic acid thus produced was separated from taurine by ion-exchange chromatography using Biorad AG resin. Fluorescamine was used as fluorogen. Data reveal that the estimation of taurine in human fetal brain regions is affected if GPE is present as a contaminant in the assay system. Cysteic acid decarboxylase activity was measured using cysteic acid as the substrate. Higher enzymic activity was recorded with increased fetal body weight, but the reverse was true for taurine level. PMID- 3346679 TI - Nicotinic agonists regulate alpha-bungarotoxin binding sites of TE671 human medulloblastoma cells. AB - The TE671 human medulloblastoma cell line expresses a variety of characteristics of human neurons. Among these characteristics is the expression of membrane-bound high-affinity binding sites for alpha-bungarotoxin, which is a potent antagonist of functional nicotinic acetylcholine receptors on these cells. These toxin binding sites represent a class of nicotinic receptor isotypes present in mammalian brain. Treatment of TE671 cells during proliferative growth phase with nicotine or carbamylcholine, but not with muscarine or d-tubocurarine, induced up to a five-fold increase in the density of radiolabeled toxin binding sites in crude membrane fractions. This effect was blocked by co-incubation with the nicotinic antagonists d-tubocurarine and decamethonium, but not by mecamylamine or by muscarinic antagonists. Following a 10-13 h lag phase upon removal of agonist, recovery of the up-regulated sites to control values occurred within an additional 10-20 h. These studies indicate that the expression of functional nicotinic acetylcholine receptors on TE671 cells is subject to regulation by nicotinic agonists. Studies of the murine CNS have consistently indicated nicotine-induced up-regulation of nicotinic acetylcholine receptors, thereby supporting the identification of the toxin binding site on these cells as the functional nicotinic receptor. Although a mechanism for this effect is not apparent, nicotine-induced receptor blockade does not appear to be involved. PMID- 3346681 TI - Preclinical and subclinical events in motor neuron disease. AB - It is suggested that in motor neuron disease there is a long preclinical period of relative tolerance and compensation before presentation with apparently focal features. During this phase the disease becomes disseminated through the motor system. The mode of acquisition of the disease, its relation to a possible genetic factor, and the processes leading to tolerance, to latency or progression, to the relative involvement of upper and lower motor neurons, to involvement of spinocerebellar pathways, and to asymmetry are fundamental problems in understanding the disease. PMID- 3346682 TI - The value of accurate clinical assessment in the surgical management of the lumbar disc protrusion. AB - One hundred patients with lumbar disc protrusions were studied. Thirty six "control" patients were admitted in the same time period with low back pain and sciatica but with subsequently "normal" myelograms and no surgery. The aim of this paper was to relate history and clinical signs to the myelograms and surgical findings. Ninety nine per cent of our patients presented with sciatica (controls 94%). The most frequently found sign in patients with a disc protrusion was reduction of ipsilateral straight leg raising (98%). However, 55% of controls also showed this sign. There were three signs that, when present, particularly indicated a disc protrusion; "crossed straight leg raising" (pain on contralateral straight leg raising), measured calf wasting and impaired ankle reflex: the latter being especially indicative of an L5-S1 disc protrusion. There were two further important signs, weakness of dorsiflexion of the foot and scoliosis of the lumbar spine. However, such signs occurred in about half the patients and so clinical diagnosis in the remaining half depended on obtaining a good history of sciatica, and paying due regard to severity of the pain, the mobility of the patient, the ability and desire to work and the overall personality. Satisfactory results of surgery simply depend on finding and removing a definite disc protrusion. Using these methods of selection, 98% have returned to their original employment, 86% within 3 months of the operation. For a patient with no abnormal signs and a normal myelogram, surgical treatment should not be advised. PMID- 3346684 TI - Stability of CT scan findings in schizophrenia: results of an 8 year follow-up study. AB - Earlier cross-sectional studies have suggested that CT findings of ventricular enlargement and increased cortical markings in schizophrenic patients are not progressive, but individual patients have rarely been followed prospectively. Fifteen patients with chronic schizophrenia were rescanned on the same model machine after 7 to 9 years of continuous illness and, in seven cases, of continuous hospitalisation. It was not possible to demonstrate significant changes in either ventricular-brain ratio or frontal atrophy scores. These results suggest that the pathologic process responsible for CT changes in schizophrenia is static and is not affected by 8 years of neuroleptic medication and institutionalisation. PMID- 3346683 TI - Neurological correlations of ejaculation and testicular size in men with a complete spinal cord section. AB - This study was of 135 patients with a complete spinal cord section suffered from loss of ejaculation. The spinal cord injuries were classified following the upper and the lower limits of the lesion. The volume of the testes of the patients and of 13 normal control subjects were measured. Physostigmine allowed 75 patients to ejaculate and 15 of them procreated. The possibility of ejaculation after physostigmine mainly depended on the integrity of the T12-L2 metamers. The testicular volume was significantly smaller in patients with a lesion including the T12 metamer than in patients with a lesion sparing the T12 metamer. Six patients with a lesion including the T12 metamer had testicular atrophy. This suggests that T12 segment plays a role in testicular function in paraplegic patients. PMID- 3346685 TI - Immunoglobulin allotypes in caucasian and Chinese myasthenia gravis: differences from Japanese patients. AB - The G2m(n) allotype was significantly increased in Chinese female and high autoantibody cases, and in caucasians with pure ocular myasthenia, or undetectable autoantibody. In contrast to the strong Glm(x) association reported in Japanese, no overall Gm haplotype, or Am or Km allotype association was found in 90 (Taiwan) Chinese and 181 caucasian myasthenia gravis patients. PMID- 3346686 TI - "Alien hand" and loss of bimanual coordination after dominant anterior cerebral artery territory infarction. AB - Three patients with dominant anterior cerebral artery territory infarction demonstrated a severe disturbance of upper limb motor control with impaired bimanual coordination, the "alien hand" sign, and intermanual conflict, in addition to signs of callosal interruption and a transcortical motor aphasia. Recordings of movement-related potentials in one patient showed an attenuated Bereitschaftspotential and a greater asymmetry of the NS' component of the premotor negativity with left finger than with right finger movement. The impairment of bimanual motor control and associated abnormal motor behaviour of the right hand in these cases are postulated to be due to involvement of the supplementary motor area and related areas of the medial frontal cortex. PMID- 3346687 TI - The control of bimanual aiming movements in Parkinson's disease. AB - The control of unimanual and bimanual aiming movements by Parkinson's disease and control subjects was examined. Despite greater bimanual movement initiation asynchrony and overall bradykinesia, the Parkinson's disease subjects were affected by the experimental manipulations in the same way as controls. Symmetrical and, more especially, asymmetrical bimanual movements required more preparation time and were executed more slowly by both groups than were unimanual movements. Both groups also showed temporal linkage of movements to targets of different extents--movements which have different movement times when performed unimanually, as well as of the faster and slower limbs. A majority in both groups over-compensated for asynchrony in bimanual movement initiation by modulation of movement times, but there was no group difference in this tendency. The results are discussed in terms of underlying motor control processes and with regard to previous evidence for impaired control of simultaneous movements in Parkinson's disease. PMID- 3346688 TI - Postural adjustments associated with rapid voluntary arm movements. II. Biomechanical analysis. AB - Normal subjects performed bilaterally symmetric rapid elbow flexions or extensions ("focal movements") while standing. Specific patterns of electromyographic activity in leg and trunk muscles ("associated postural adjustments") were seen for each type of movement. The biomechanical significance of these postural adjustments was analysed by means of the ground reaction forces and motion of the various body segments. Experimental data were compared with that from a theoretical model of the body consisting of a six segment kinetic chain with rigid links. Distinct patterns of the ground reaction forces with elbow flexion were opposite in direction to those seen with elbow extension. Movements of the various body segments were small and specific for a certain focal movement. Dynamic perturbations arising from the arm movement in an anteroposterior direction were found to be compensated by postural adjustments, whereas vertical perturbations were not compensated. The muscular activity acting about different joints in the different movements was found to correlate with the predictions of activity needed to compensate for net joint reaction moments arising from the focal movement. Motion of the various body segments could be understood as resulting from the interplay of the net reaction moments and the net muscular moments at the different joints. Dynamic postural requirements are accomplished by a precise active compensation initiated before the focal movement. PMID- 3346689 TI - The effect of age of disease onset on neuropsychological performance in Parkinson's disease. AB - One hundred and eight noninstitutionalized patients with Parkinson's disease were studied to find out whether the age of disease onset affects patients' cognitive, memory and psychomotor performance. "Early onset" patients (whose disease began before 60 years of age) showed a wide spectrum of impairments in neuropsychological performance compared with age-matched normal subjects. However, only one (2%) of these patients was demented according to DSM III criteria. Dementia was more frequent in patients with equivalent disease duration, but with late onset of disease (over 60 years); 13 of such patients (25%) were demented. The present study supports previous findings which show that dementia increases with advancing age in Parkinson's disease. It also suggests that cognitive changes are also found in patients with early onset of disease. PMID- 3346690 TI - A new metabolic muscle disease due to abnormal hexokinase activity. AB - A 34 year old man presented with an 8 year history of mild muscle pain and stiffness on exertion especially in the cold. Clinical examination was normal. Apart from a mild persistent leucocytosis, his routine investigations were normal including creatine kinase activity, electromyography and nerve conduction studies. An ischaemic exercise test produced a slow and incomplete rise in lactate. Histological examination showed non-specific myopathic changes in some quadriceps femoris muscle fibres. Investigation of muscle metabolism by spectrofluorometric analysis of muscle enzyme activity and by muscle fibre incubation studies revealed a severe defect in glucose phosphorylation, associated with an electrophoretically abnormal hexokinase. Further metabolic studies suggest that the block in glucose metabolism is by-passed via an enhanced phosphorylation of fructose by the abnormal hexokinase. PMID- 3346691 TI - Perivascular iron deposition and other vascular damage in multiple sclerosis. AB - Evidence of damage to cerebral vein walls was sought in 70 cases of multiple sclerosis. Seventy control cases were also examined. The multiple sclerosis cases showed venous intramural fibrinoid deposition (7%), recent haemorrhages (17%), old haemorrhages revealed by haemosiderin deposition (30%), thrombosis (6%) and thickened veins (19%). In all, 41% of all multiple sclerosis cases showed some evidence of vein damage. Occasional control cases showed haemosiderin deposition in the brain but, unlike the multiple sclerosis cases, these were diffuse and almost entirely related to coexistent cardiovascular or cerebrovascular disease. Haemosiderin deposition was common in the substantia nigra and other pigmented nuclei in all cases. It is concluded that the cerebral vein wall in multiple sclerosis is subject to chronic inflammatory damage, which promotes haemorrhage and increased permeability, and constitutes a form of vasculitis. PMID- 3346692 TI - Transient feelings of compulsion caused by hemispheric lesions: three cases. AB - There was strong evidence of a neurological explanation for transient feelings of compulsion reported by three patients. In at least two cases the mechanism was epileptic. The frontal lobe was implicated in all three. A feeling of compulsion, divorced from action, has rarely if ever been reported in epilepsy or other neurological disorders. PMID- 3346693 TI - The variable clinical and CT findings after carotid occlusion: the role of collateral blood supply. AB - A retrospective review of 61 cases of angiographically confirmed occlusion of one or both carotid arteries was carried out to look at the evidence that the presence of collateral blood supply influenced the extent and type of cerebral infarction. Forty six patients had bilateral angiography from which it was possible to assess collateral filling of the internal carotid and middle cerebral arteries. As expected, patients with no CT scan evidence of infarction more frequently had transient ischaemic attacks or retinal infarcts than did those with visible cerebral infarcts. Patients with small cortical ischaemic lesions usually had appropriate neuropsychological or neurological deficits. Three patients with cortical watershed infarcts had a fluctuating deficit. Of the patients with bilateral angiograms 67% showed some filling via collaterals of the middle cerebral artery, and 43% of the internal carotid artery in the siphon. Those with collateral filling were mostly found to have normal CT scans or evidence of peripheral cortical lesions. By contrast most watershed and full territory infarcts were found in individuals whose angiograms showed no collateral filling. It is suggested that in many cases infarction occurs despite collateral flow and is due to distal embolism and that this may be relevant to the recently reported failure of the EC/IC bypass operation. PMID- 3346694 TI - The frequency, characteristics and prognosis of epileptic seizures at the onset of stroke. AB - In a series of 230 patients admitted to hospital with a stroke, the frequency and significance of epileptic seizures at onset was assessed. Thirteen (5.7%) suffered single or multiple witnessed seizures at the onset of their stroke. Seizures were evenly distributed among all pathological stroke sub-types but were restricted to lesions in the carotid artery territory. They indicated a poorer prognosis over the first 2 days. Six of the 13 presenting with stroke and seizures had prior seizures and, if they survived, continued to have fits. The five patients surviving with stroke and a first seizure were all fit-free after 30 months follow-up. PMID- 3346695 TI - Multiple sclerosis presenting as chronic atypical psychosis. AB - Two patients with multiple sclerosis are reported in whom psychopathological symptoms were present for many years. An exact psychiatric classification of the clinical syndrome was not possible. At no time during the illness were abnormal neurological findings observed. Multiple sclerosis was proven following necropsy in one patient. In the second patient a possible diagnosis of multiple sclerosis was made. This patient was found to have multiple lesions in the white matter which were evident on MRI and in the isoelectric focusing (IEF) of cerebrospinal fluid oligoclonal bands were found. PMID- 3346696 TI - Methylprednisolone therapy in multiple sclerosis: a profile of adverse effects. AB - A retrospective analysis of 350 treatment courses using high dose pulsed intravenous methylprednisolone for relapses of multiple sclerosis revealed a low number of adverse effects. This study confirms that high dose methylprednisolone is a safe therapeutic option in multiple sclerosis. PMID- 3346697 TI - Haemangiopericytic meningioma of the sacral canal: a case report. AB - A case of haemangiopericytic meningioma of the sacral canal in a 25 year old man, an uncommon tumour at a rare site, is described. The tumour was malignant and largely undifferentiated although there was light and electron microscopic evidence of dual differentiation in areas towards haemangiopericytoma and meningioma. The patient, with cauda equina syndrome, was treated by partial resection and post-operative radiotherapy and remains well 12 months after treatment. PMID- 3346698 TI - Peripheral neuropathy associated with erythrophagocytic lymphohistiocytosis. AB - A 12 year old patient who developed clinical, biochemical and histological features of erythrophagocytic lymphohistiocytosis is described. In contrast to previously reported cases, the prominent neurological feature was a subacute sensorimotor polyneuropathy. Sural nerve biopsy showed a marked reduction of myelinated fibres and severe axonal lesions, absence of histiocyte infiltration and deposits of IgM along the epineurium. In addition to the hypertriglyceridaemia previously described in this condition, an elevation of plasma very long-chain fatty acids and phytanic acid was found which suggests a transient impairment of peroxisomal functions. PMID- 3346699 TI - Familial carnitine deficiency: further evidence for autosomal recessive transmission with variable expression. AB - Carnitine deficiency occurring in families has been rarely reported and the genetic transmission has not yet been clearly elucidated. Five members of one family showing marked heterogeneity of carnitine deficiency states are presented. In three patients, there was no correlation between measurable carnitine levels in serum and muscle and the clinical findings. The parents, who are remote relatives from an isolated village in Kurdistan (Iraq), had low muscle carnitine levels; however, they were asymptomatic. One son, with systemic carnitine deficiency causing muscle weakness and recurrent episodes of severe hepatic encephalopathy, died at 3 years of age. His brother had mild proximal muscle weakness associated with low muscle carnitine levels. He was successfully treated with L-carnitine and prednisone. A daughter is asymptomatic, but with low serum and muscle levels of carnitine. The marked heterogeneity of carnitine deficiency states within one family, where both parents had low muscle carnitine levels, suggests an autosomal recessive inheritance with variable expression. PMID- 3346701 TI - Cerebral infarction on CT scans in patients with transient ischaemic attacks relates to severity of angiographic disease at the carotid bifurcation. PMID- 3346702 TI - Subarachnoid hemorrhage from spinal tumor (in the absence of spinal symptoms or signs) PMID- 3346700 TI - Race-gender differences in serum creatine kinase activity: a study among South Africans. AB - Higher levels of total serum creatine kinase activity have been reported in black compared with white North Americans of the same sex. In a study among South Africans, we found such an interracial difference was notable only for males. The difference was heightened by physical activity. This study affirms the importance of sampling the indigenous population when developing a reference range for total creatine kinase activity. PMID- 3346703 TI - Operculum syndrome from brain abscess in a left-hander. PMID- 3346704 TI - Nocardia asteroides infection of the cauda equina. PMID- 3346706 TI - Visual evoked potentials and neopterin: biopterin ratios in urine show a high correlation in Alzheimer's disease. PMID- 3346707 TI - Paradoxical reversal of ptosis in myasthenia gravis by edrophonium administration. PMID- 3346705 TI - Relapsing dermatomyositis associated with sarcoidosis. PMID- 3346708 TI - Nifedipine in the treatment of myotonia. PMID- 3346709 TI - Do white matter changes on MRI and CT differentiate vascular dementia from Alzheimer's disease? PMID- 3346710 TI - Temporal profile of thromboxane-prostacyclin imbalance in experimental spinal cord injury. AB - Thromboxane-prostacyclin imbalance may be an important determinant of platelet vessel wall interactions that are vital in circulatory homeostasis. In experimental spinal cord injury, the vascular damage contributes substantially to the process of progressive secondary injury culminating in post-traumatic myelopathy. In this study, we found a time-dependent alteration of thromboxane prostacyclin balance in the injured spinal cord with thromboxane dominance during the first 2 h: a time when maximal vascular injury is reflected by extravasation of 125I-labelled serum albumin. The thromboxane-prostacyclin imbalance reverted to favor prostacyclin by 18 h post-injury. This time-dependent alteration of thromboxane-prostacyclin balance should be considered in the planning of therapeutic attempts to prevent secondary injury by pharmacological modulation of platelet-vessel wall interaction. PMID- 3346711 TI - Increased dermal collagen density in amyotrophic lateral sclerosis. AB - We examined specimens of skin overlying the sacral region, among the most common sites of bedsores, from patients with amyotrophic lateral sclerosis (ALS) and controls, and found that in ALS patients, collagen fibrils had a greater density and became more tightly packed with the duration of illness. Our results suggest that the increased density of collagen fibrils may protect the skin of ALS patients from pressure ischemia, a major cause of bedsore formation. PMID- 3346712 TI - Migration and differentiation of neural crest and ventral neural tube cells in vitro: implications for in vitro and in vivo studies of the neural crest. AB - During vertebrate development, neural crest cells migrate from the dorsal neural tube and give rise to pigment cells and most peripheral ganglia. To study these complex processes it is helpful to make use of in vitro techniques, but the transient and morphologically ill-defined nature of neural crest cells makes it difficult to isolate a pure population of undifferentiated cells. We have used several established techniques to obtain neural crest-containing cultures from quail embryos and have compared their subsequent differentiation. We confirm earlier reports of neural crest cell differentiation in vitro into pigment cells and catecholamine-containing neurons. However, our results strongly suggest that the 5-HT-containing cells that develop in outgrowths from thoracic neural tube explants are not neural crest cells. Instead, these cells arise from ventral neural tube precursors that normally give rise to a population of serotonergic neurons in the spinal cord and, in vitro, migrate from the neural tube. Therefore, results based on previously accepted operational definitions of neural crest cells may not be valid and should be reexamined. Furthermore, the demonstration that cells from the ventral (non-neural crest) part of the neural tube migrate in vitro suggests that the same phenomenon may occur in vivo. We propose that the embryonic "neural trough," as well as the neural crest, may contribute to the PNS of vertebrates. PMID- 3346713 TI - Preferential reinnervation of motor nerves by regenerating motor axons. AB - Regeneration of axons into inappropriate distal nerve branches may adversely affect functional recovery after peripheral nerve suture. The degree to which motor axons reinnervate sensory nerves, and vice versa, has not been determined. In these experiments, HRP is used to quantify the sensory and motor neurons that reinnervate sensory and motor branches of the rat femoral nerve after proximal severance and repair. Motoneurons preferentially reinnervate the motor branch in juveniles and adults, even if the repair is intentionally misaligned or a gap is imposed between proximal and distal stumps. A specific interaction thus occurs between regenerating motor axons and the Schwann cell tubes that lead to the motor branch. This interaction is independent of mechanical axon alignment. PMID- 3346714 TI - Developmental changes in Ca2+/calmodulin-dependent protein kinase II in cultures of hippocampal pyramidal neurons and astrocytes. AB - We have analyzed Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) localization, activity, and endogenous protein substrates during differentiation and synaptogenesis in cultured hippocampal neurons. Primary cultures from hippocampi from 18 d embryonic rats are composed primarily of pyramidal neurons, with minimal contamination by nonneuronal cells. We have used monoclonal (Mab) and affinity-purified polyclonal antibodies that recognize either or both of the subunits of CaM-kinase II in order to localize the enzyme at progressive stages of neuronal differentiation. Diffuse but specific binding, determined by indirect immunofluorescence analyses, was first detected in cell bodies and growth cones of pyramidal neurons after 4 d in culture. Immunoreactivity increased during the next 3 d of culture, at which time fluorescent, labeling was patchy along neuritic processes. By 10 d, intensely fluorescent, discrete spots were observed along processes and on cell bodies. Astrocyte cultures prepared from newborn rat cortex showed no detectable immunofluorescence with anti-CaM-kinase II antibodies. Cytosolic and particulate fractions from cultured pyramidal neurons and astrocytes were analyzed using immunoblot, in vitro phosphorylation, 2 dimensional gel electrophoresis, and phosphopeptide mapping techniques. Although pure astrocyte cultures contained low levels of Ca2+/CaM-stimulated protein kinase activity, they did not display detectable levels of immunoreactive 50 kDa subunit nor 50 and 60 kDa phosphoproteins analogous to the autophosphorylated subunits of CaM-kinase II. Immunoblot analysis detected the 60 kDa kinase subunit in particulate and cytosolic fractions from 2 d neurons. By contrast, the 50 kDa subunit of CaM-kinase II was not detected in cytosolic or particulate fractions of pyramidal neurons before 4 d in culture. In 2 d pyramidal neuron cultures, only low levels of Ca2+/CaM-stimulated protein phosphorylation were observed. Ca2+/CaM-dependent phosphorylation of 10 d pyramidal cell proteins was 3-5-fold greater than that of 2 d cultures, and included major phosphoproteins of 48, 50, 56, 58/60, 80-86, 90, 120, 138, 175, and 190 kDa. Phosphopeptide maps of 58/60 and 50 kDa phosphoproteins gave patterns very similar to those of the autophosphorylated 60 and 50 kDa subunits, respectively, of purified CaM-kinase II. A phosphoprotein doublet of 83 kDa was identified as synapsin I. Developmental changes in Ca2+/CaM-dependent phosphorylation in pyramidal neuron cultures were very similar to those previously described in subcellular fractions from postnatal rat forebrain. PMID- 3346715 TI - Autoradiographic localization and biochemical characteristics of M1 and M2 muscarinic binding sites in the striatum of the cat, monkey, and human. AB - The autoradiographic distribution of M1 and M2 muscarinic cholinergic binding sites was studied in the striatum of the cat, monkey, and human, and concurrent binding assays were carried out on striatal tissue sections from the cat. M1 sites were directly labeled with 3H-pirenzepine; M2 sites were labeled as a consequence of binding competition between pirenzepine and 3H-N methylscopolamine. Serial section analysis with autoradiograms and stained tissue sections allowed for comparisons among M1 and M2 binding distributions and AChE staining patterns. The 2 subtypes of binding sites demonstrated distinct striatal distributions. M2 sites were virtually homogeneous except in the ventral striatum, where zones of sparse and especially dense binding were observed. Striatal M1 sites were generally more abundant than M2 sites and showed similar heterogeneity in the ventral striatum. Dorsally, however, patches of dense M1 binding were found, and proved to correspond with AChE-poor striosomes, hallmarks of striatal compartmentalization. The finding of differing distributions for the 2 subtypes of muscarinic cholinergic binding sites suggests a mechanism for the intrinsic spatial segregation of striatal cholinergic function. Further, the striosomal patterning of M1 binding indicates that certain aspects of cholinergic function in the striatum may be constrained and thus regulated by the compartmental ordering characteristic of this region of the basal ganglia. PMID- 3346716 TI - A tecto-rotundo-telencephalic pathway in the rattlesnake: evidence for a forebrain representation of the infrared sense. AB - Rattlesnakes possess a sensory system specialized for the detection of infrared (IR) radiation. IR signals ascend as far as the optic tectum, where they generate a spatiotopic map. It is unknown if such signals reach the forebrain, but the existence of prominent tectothalamic pathways in other vertebrates makes this a distinct possibility. In nonmammalian forms, the major target of ascending tectal visual signals is nucleus rotundus, a thalamic nucleus that projects in turn to the subpallial telencephalon. We sought to determine whether a tecto-rotundo telencephalic system exists in rattlesnakes and, if so, whether it carries IR as well as visual information. We have identified a thalamic nucleus in the rattlesnake Crotalus viridis that matches the n. rotundus of other reptiles in its topographic location, cytoarchitecture, and connections. Using anterograde and retrograde transport of HRP, we have demonstrated a strong ipsilateral and weaker contralateral tectorotundal projection. Tectorotundal cells lay primarily in the deeper tectal layers, which receive input from the IR system, but also in the superficial, visual layers. In n. rotundus, single units recorded extracellularly invariably responded to visual stimuli, but many were also sensitive to unimodal IR stimuli. IR and visual receptive fields were very large and often bilateral. Some rotundal units appeared sensitive to substrate vibration. Most habituated rapidly. Nucleus rotundus was found to project to a sector of the ipsilateral anterior dorsal ventricular ridge (ADVR) of the telencephalon. Single units in this region of the ADVR resembled those in rotundus, responding to visual, IR, and/or vibrational stimuli and possessing large, often bilateral receptive fields. These findings demonstrate the existence of a tecto-rotundo-telencephalic pathway in rattlesnakes and suggest that this system conveys IR as well as visual information to the forebrain. Ascending tectofugal pathways have been implicated in the discrimination of form. Thus, pattern recognition may have to be added to orientation as a proper function of the IR system of pit vipers. PMID- 3346717 TI - Development and survival of neurons in dissociated fetal mesencephalic serum-free cell cultures: I. Effects of cell density and of an adult mammalian striatal derived neuronotrophic factor (SDNF). AB - The use of CNS cultures for detection and quantification of neuronotrophic activity in the CNS has been analyzed. In particular the development, i.e., neurotransmitter uptake characteristics, and survival of dopaminergic and GABAergic neurons in fetal mouse (E13)-dissociated mesencephalic cells cultured in serum-free, hormone-supplemented medium have been assessed as a function of culture time and cell density. At all times, more than 98% of the cells were classified as neurons on the basis of immunocytochemical criteria. Results indicate that the increase of cell density in vitro significantly enhances specific high-affinity dopamine uptake per dopaminergic cell and cell survival. This effect is not limited to the dopaminergic cells and suggests that the development of neurotransmitter-related traits and cell survival are influenced by cell density-derived trophic signals. The above-mentioned cultures and parameters have also been used to detect neuronotrophic activity in adult mammalian brain extracts or more purified preparations. In particular, bovine striatal extracts contain activity capable of increasing high-affinity neurotransmitter uptake parameters and cell survival of at least the dopaminergic and GABAergic neurons present in the culture system. The neuronotrophic activity from bovine striatum has been partially purified and is associated with a fraction whose main component is a basic protein of approximately 14 kDa. PMID- 3346718 TI - Development and survival of neurons in dissociated fetal mesencephalic serum-free cell cultures: II. Modulatory effects of gangliosides. AB - This paper analyzes the effects of exogenously supplied GM1 on the development, i.e., specific neurotransmitter uptake capability and survival, of the dopaminergic neurons present in fetal mouse-dissociated mesencephalic cells. Exogenous GM1, but not asialo-GM1, sialic acid, or the oligosaccharide chain of GM1, enhances in a time- and concentration-dependent manner the specific 3H dopamine uptake (increase of the apparent Vmax and decrease of the apparent Km value) and the long-term survival of the dopaminergic neurons. The GM1 effects on the behavior of the dopaminergic neurons require the presence of cell-derived neuronotrophic influences present within the culture system and are associated with an increase in the response of the cells to the trophic influences. GM1 effects are not limited to dopaminergic neurons, and depend on the stable association of the ganglioside molecule with the cells. It is suggested that GM1 is not a trophic agent per se, but rather potentiates neuronotrophic activities and/or exerts independent influences to which neurons respond only if appropriately supported. PMID- 3346719 TI - Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor. AB - Although cells firing at tremor frequency, called "tremor cells" (Guiot et al., 1962), have often been recorded in the thalamus of parkinsonian patients, the extent of correlation between these spike trains and tremor has rarely been assessed quantitatively. This paper describes spectral cross-correlation functions calculated between the activity of "tremor cells" and electromyogram (EMG) signals recorded from several muscles in the contralateral arm. The power occurring in the spike train at tremor frequency was described in absolute terms by the spike autopower, and in relation to the average for all spectral components by the spike autopower signal-to-noise ratio (spike autopower SNR). The probability of significant cross-correlation between the thalamic spike train and EMG at tremor frequency was assessed by the coherence at tremor frequency. Autopower spectra of the activity of many of these cells exhibited a concentration of power at tremor frequency, indicated by spike autopower SNRs as high as 18. Of the EMG signals studied, signals recorded from finger flexors were most often significantly correlated at tremor frequency. Significant correlation between the thalamic spike train and finger flexor EMG activity was found in 34% of cells analyzed. Tremor frequency coherence was significantly correlated with tremor frequency spike autopower (r = 0.46, p less than 0.0001) and spike autopower SNR (r = 0.533, p less than 0.0001). The proportion of cells with a spike autopower SNR greater than 2 that were significantly correlated with finger flexor EMG activity was greater than that of cells with a spike autopower SNR of less than 2 (p less than 0.001; chi-square). Therefore, cells exhibiting a large amount of power at tremor frequency were those best correlated with EMG activity during tremor. Some of these cells may be involved in the generation of tremor. PMID- 3346721 TI - Superinnervation enhances the dendritic branching pattern of the Mauthner cell in the developing axolotl. AB - Mauthner cells (M-cells) occur as a pair of large, uniquely identifiable neurons at ear level in the hindbrain of premetamorphic amphibians. Each receives synapses from the ipsilateral vestibular nerve (nVIII); these morphologically distinctive terminals, or club endings, are confined to the proximoventral surface and branches of the M-cell lateral dendrite. We have superinnervated this portion of the M-cell to examine the extent to which forming afferent contacts regulate the growth and branching of the lateral dendrite. Superinnervation was brought about in the developing axolotl (Ambystoma mexicanum) by unilaterally implanting an extra vestibular primordium rostral to the in situ one. The contralateral side served as control. When the larvae reached 21 mm in length, the ectopic nerve was labeled with HRP. Subsequent microscopic examination revealed that the grafts developed into anatomically normal ears. The HRP-labeled ectopic axons entered the medulla at the level of nV and confined to the nVIII tract, coursed caudad toward the ipsilateral M-cell. Electron microscopic analysis demonstrated labeled club endings on the appropriate region of the M cell lateral dendrite. The number of club endings on experimental M-cells was significantly greater than that on the contralateral controls, and the extra terminals appeared to be distributed randomly among unlabeled ones. Comparison of reconstructed experimental and control M-cells revealed that superinnervation produced a localized enhancement of dendritic branching in the region receiving the extra nVIII synapses. In the donor embryos (those from which the vestibular primordium was removed), M-cells were unilaterally deprived of nVIII afferents. Comparison of reconstructed experimental and control M-cells in 21 mm donor larvae demonstrated that deprivation produced a localized decrease of dendritic surface in the region that normally receives nVIII synapses. Together, these data show that ingrowing axons stimulate dendritic growth and thus regulate the development of a normal dendritic branching pattern on target neurons. PMID- 3346720 TI - Hormonal regulation of the shape of identified motoneurons in the moth Manduca sexta. AB - Motoneurons MN-1 and MN-3 in the moth Manduca sexta go through 3 distinct phases during postembryonic life. During larval life their neuritic fields show allometric growth in concert with larval growth. Larval neurites are then lost during the larval-pupal transition, which is followed by the outgrowth of adult specific neurites during adult development. In MN-1, the adult-specific arbor typically results from the outgrowth of neurites ipsilateral to the cell body. However, in a small percentage of cells, ipsilateral branches are not present and contralateral branches extend across the midline to fill the vacant space. This altered form of MN-1 is thought to result from the early failure of ipsilateral neurite extension. The steroid hormones, the ecdysteroids, are responsible for the outgrowth of adult neurites. The onset of the latter is correlated with the ecdysteroid increase that promotes adult differentiation and does not occur under conditions such as diapause, in which the normal steroid rise is absent. Artificial replacement of ecdysteroids, however, induces the adult-specific growth. This action of ecdysteroids to cause a change in neuronal form requires the absence of juvenile hormone (JH). Application of JH mimics prior to the onset of the program of adult outgrowth blocks this outgrowth. MN-1 and MN-3 show different times of JH sensitivity, which appear to be correlated with different times of neurite outgrowth. It is concluded that the role of JH is to maintain the status quo of central neurons and prevent changes in form in response to ecdysteroids. In the absence of JH, the ecdysteroids can then exert morphogenetic changes, but the nature of these actions, neurite outgrowth or regression, is likely a function of the developmental history of the cell. PMID- 3346722 TI - Development of voltage-dependent calcium, sodium, and potassium currents in Xenopus spinal neurons. AB - Action potentials of embryonic nerve and muscle cells often have a different ionic dependence and longer duration than those of mature cells. The action potential of spinal cord neurons from Xenopus laevis exhibits a prominent calcium component at early stages of development that diminishes with age as the impulse becomes principally sodium dependent. Whole-cell voltage-clamp analysis has been undertaken to characterize the changes in membrane currents during development of these neurons in culture. Four voltage-dependent currents of cells were identified and examined during the first day in vitro, when most of the change in the action potential occurs. There are no changes in the peak density of the calcium current (ICa), its voltage dependence, or time to half-maximal activation; a small increase in inactivation is apparent. The major change in sodium current (INa) is a 2-fold increase in its density. In addition, more subtle changes in the kinetics of the macroscopic sodium current were noted. The peak density of voltage-dependent potassium current (IKv) increases 3-fold, and this current becomes activated almost twice as fast. No changes were noted in the extent of its inactivation. The calcium-dependent potassium current (IKc) consists of an inactivating and a sustained component. The former increases 2 fold in peak current density, and the latter increases similarly at less depolarized voltages. The changes in these currents contribute to the decrease in duration and the change in ionic dependence of the impulse. PMID- 3346723 TI - Optokinetic nystagmus: modeling the velocity storage mechanism. AB - To account for the oscillatory behavior of the optokinetic after-nystagmus (OKAN), a nonlinear model of the optokinetic system is proposed here that includes 2 first-order storage elements interconnected in a negative feedback loop. The adequacy of the model is tested by comparing its predictions with experimental data available in the literature. In addition, the question of the contribution of the storage element responsible for secondary OKAN (OKAN II) to the dynamic properties of the optokinetic nystagmus (OKN) is addressed. The results show that the model is compatible with all modifications of the OKAN time course observed under various experimental situations. By comparing computer simulations and experimental data, it is inferred that (1) the dynamic properties of the optokinetic system during OKN and during OKAN are different; (2) the switching in velocity storage dynamics is not determined by the light-dark transition, but is induced whenever nystagmic slow phase velocity (SPV) is not sustained by an appropriate retinal slip error signal; (3) although no signs of adaptation are seen during OKN, the storage element responsible for OKAN II becomes charged during optokinetic stimulation; and (4) the time constants of the integrators are affected by the parameters of the preceding optokinetic stimulation. PMID- 3346724 TI - Recovery of tactile function after damage to primary or secondary somatic sensory cortex in infant Macaca mulatta. AB - These studies were designed to determine the basis for recovery of tactile function after the removal of primary (SI) or secondary (SII) cortex in infant Macaca mulatta. From previous studies we know that although removal of SI or SII in the adult macaque produces severe and irreversible impairment on a variety of tactile tasks, normal function can be obtained after partial or total SI lesions in the infant. From the present studies we have found that, as with SI, neither unilateral nor bilateral removals of SII in infants significantly affected the acquisition of or the performance on size tasks, but did cause a temporary delay in acquisition of texture tasks. Performance on texture threshold tasks was normal. The removal of the remaining SI in a juvenile animal that had received a unilateral SI lesion in infancy did not disrupt the recovered function, indicating that recovery is not mediated by the intact SI. However, when SI and SII were removed together from the same hemisphere in an infant, either sequentially or simultaneously, major impairment in the acquisition of texture tasks followed. These results suggest that although SI and SII are necessary for normal tactile function in the adult macaque, they show an equipotentiality for mediating normal tactile function after damage to either area in infants. PMID- 3346726 TI - Redistribution and internalization of antibodies to galactocerebroside by oligodendroglia. AB - Glial cultures from mouse brain were used to examine the direct interaction between oligodendroglia and antibodies to galactocerebroside (GalC). The external surface of oligodendroglial membrane sheets showed large GalC+ patches separated by a GalC- network after exposure to anti-GalC and fluoresceinated second antibody at 37 degrees C. However, the membrane sheets were evenly stained when cultures were fixed prior to staining or stained at 0 degrees C. Further, exposure to second antibody at 0 degrees C or to Fab fragments of second antibody at 37 degrees C also gave even staining. These results indicate that GalC is normally distributed evenly on the surface of oligodendroglial membrane sheets, but that redistribution or patching of GalC:anti-GalC complexes occurs by cross linking with second antibody at 37 degrees C. Antibodies to GalC are internalized rapidly and specifically by oligodendroglia. This process is temperature dependent, and, in contrast to patching, does not require the presence of second antibody. Internalized antibodies are seen within 1 min throughout oligodendroglial membrane sheets, then aggregate in the sheets and in large vein like structures leading to the cell body. By 1 hr, the cell body is densely packed with vesicles containing anti-GalC. By 24 hr after a 10 min exposure to anti-GalC, internal antibody has disappeared. Anti-GalC is recycled to the cell surface within 5 min after exposure, and continues to appear on the surface for at least 4 hr after the pulse. PMID- 3346725 TI - Expression of a surface-associated antigen on Y-cells in the cat lateral geniculate nucleus is regulated by visual experience. AB - The monoclonal antibody Cat-301, generated against cat spinal cord (McKay and Hockfield, 1982), recognizes a surface-associated antigen that, in the cat lateral geniculate nucleus (LGN), is selectively expressed on Y-cells (Hockfield et al., 1983; Hendry et al., 1984; Sur et al., 1984). We now report that the antigen recognized by Cat-301 appears late in development, along a time course similar to that described for the maturation of the physiological properties of Y cells in the LGN, and that its expression is sharply reduced by monocular lid suture or dark-rearing from birth, 2 visual deprivation procedures that lead to a reduction in the proportion of Y-cells recorded physiologically in the LGN (Sherman et al., 1972; Kratz et al., 1979; reviewed in Sherman and Spear, 1982). Monocular lid suture in the adult has no effect on Cat-301 antigen levels or, as previously reported (Sherman et al., 1972), on the proportion of physiologically recorded Y-cells. In addition, reversing the monocular deprivation in adulthood by opening the neonatally sutured eye and suturing closed the previously normal eye for 6 months restores neither normal levels of Cat-301 labeling nor, as previously reported (Geisert et al., 1982), the proportion of recordable Y-cells. The development of Cat-301 immunoreactivity thus parallels the development of LGN Y-cell physiology. The relative reduction in levels of immunoreactivity consequent to neonatal, but not adult, visual deprivation shows that Cat-301 antigen expression does not simply reflect the level of visually evoked electrical activity in the LGN, but rather reflects a process that depends on the nature of visual experience early in life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346727 TI - Three-dimensional pattern of enkephalin-like immunoreactivity in the caudate nucleus of the cat. AB - Recent anatomical investigations of the mammalian neostriatum have uncovered discrete neurochemical zones characterized by low levels of AChE and high levels of enkephalin-like immunoreactivity (ELI) compared with the surrounding neostriatal tissue. These regions, termed striosomes, which appear as patches in individual sections, have been associated with specific afferent and efferent pathways that differ from those of the surrounding neostriatal tissue. In the present study, the 3-dimensional distribution of these enkephalin-rich compartments in the caudate nucleus of the adult cat was investigated using computer-assisted 3-dimensional reconstruction techniques. Series consisting of coronal, sagittal, and horizontal tissue sections were obtained. In individual sections, discrete patches of intense enkephalin-like immunoreactivity appeared against a lighter-staining background. Three-dimensional reconstructions revealed that these patches overlapped across sections to form a highly inter-connected structure within the head and body of the caudate nucleus. Several structural features were evident in these reconstructions that appeared to be similar across animals. One consistent pattern was the formation of enkephalin-labeled finger like structures radiating from the ventricular edge diagonally across the width of the nucleus. Smaller crossbridges were seen connecting the fingers, which often resulted in the formation of claws or rings of enkephalin-like immunoreactivity. These elements appear to align across planes to form a lattice like structure outlining continuous regions of matrix. This structure may provide a basis for the orderly interaction between the patch and matrix compartments. PMID- 3346728 TI - Afferent influences on brain stem auditory nuclei of the chicken: presynaptic action potentials regulate protein synthesis in nucleus magnocellularis neurons. AB - Studies of the avian auditory system indicate that neurons in nucleus magnocellularis (NM) and nucleus laminaris of young animals are dramatically altered by changes in the auditory receptor. We examined the role of presynaptic activity on these transneuronal regulatory events. TTX was used to block action potentials in the auditory nerve. TTX injections into the perilymph reliably blocked all neuronal activity in the cochlear nerve and NM. Far-field recordings of sound-evoked potentials revealed that responses returned within 6-12 hr after a single TTX injection. Changes in protein synthesis by NM neurons were measured by determining the incorporation of 3H-leucine using autoradiography. NM neurons on the side of the brain ipsilateral to the TTX injection were compared to normally active cells on the other side of the same tissue section. Grain counts over individual neurons revealed that a single injection of TTX produced a 40% decrease in grain density in ipsilateral NM neurons within 1.5 hr after the TTX injection. However, by 24 hr after a single TTX injection, grain densities were not different on the 2 sides of the brain. Continuous activity blockade for 6 hr caused the cessation of amino acid incorporation in a portion of NM neurons and a 15-20% decrease in the remaining neurons. These changes in amino acid incorporation are comparable to those following complete removal of the cochlea (Steward and Rubel, 1985). We also examined NM for neuron loss and soma shrinkage after blocking eighth nerve action potentials. TTX injected every 12 hr for 48 hr caused a 20% neuron loss and an 8% shrinkage of the remaining neurons. Similar reductions were found following cochlea removal (Born and Rubel, 1985). It is concluded that neuronal activity plays a major role in the maintenance of normal NM neurons. Furthermore, these results suggest that transneuronal morphological changes seen in neurons following deafferentation or alterations of sensory experience are a result of changes in the level of presynaptic activity. PMID- 3346729 TI - Genesis of GABA-immunoreactive neurons in the ferret visual cortex. AB - The pattern of neurogenesis of GABA-immunoreactive neurons in the ferret primary visual cortex was determined using immunohistochemical and 3H-thymidine autoradiographic techniques. Neurons in the visual cortex of the ferret undergo their final cell division during a period extending from embryonic day 20 (E20) to postnatal day 14 (P14) and follow an inside-out pattern of neuronal production (Jackson et al., 1984) similar to that observed in other mammals. Earlier generated neurons are found at deeper cortical positions in the adult than are those generated later. Layer I is an exception to this rule, since neurons destined for this layer are produced at both the beginning and end of neurogenesis. In this study, the pattern of neurogenesis of GABA-immunoreactive neurons is compared to the pattern observed for nonimmunoreactive neurons. The overall pattern of cortical neurogenesis (inside-out pattern) is similar for GABA immunoreactive neurons and neurons that are not GABA-immunoreactive. However, the GABA-immunoreactive neurons born on a given day of development are more broadly distributed across the radial axis of the adult cortex than are nonimmunoreactive neurons generated on the same day. GABA-immunoreactive neurons generated later in neurogenesis are, on average, slightly smaller than those generated early. If GABA-immunoreactive neurons in the visual cortex are interneurons, then these findings suggest that interneurons follow the same pattern of neurogenesis as do projecting neurons in the visual cortex. PMID- 3346730 TI - A synapse-specific carbohydrate at the neuromuscular junction: association with both acetylcholinesterase and a glycolipid. AB - With the aim of investigating the roles of carbohydrates in synapse formation, we have characterized a synapse-specific saccharide at the vertebrate neuromuscular junction. Two lectins of similar specificity (Dolichos biflorus agglutinin, DBA, and Vicia villosa-B4 agglutinin, VVA-B4) stain synaptic but not extrasynaptic regions of the rat muscle fiber surface and thus define a synapse-specific carbohydrate. Using these and other probes, we show that the carbohydrate moiety concentrated at the neuromuscular junction resembles N-acetylgalactosamine (GalNAc) linked in the beta-anomeric form to the termini of oligosaccharides. VVA B4 also selectively stains neuromuscular junctions in human, mouse, rabbit, guinea pig, chick, frog, axolotl, snake, fish, and lamprey muscles, a phylogenetic conservatism that suggests a synapse-related role for GalNAc beta terminal saccharides. AChE from muscle binds to DBA- and VVA-B4-agarose, and is thereby identified as a glycoconjugate bearing the synapse-specific carbohydrate. Assay of AChE isoforms reveals that asymmetric, collagen-tailed forms, known to be highly concentrated at the rat neuromuscular junction, bind DBA and VVA-B4, while globular forms, which are more widely distributed, do not. A second class of GalNAc-bearing glycoconjugates is demonstrable immunohistochemically with monoclonal antibodies to stage-specific embryonic antigen (SSEA)-3 (Shevinsky et al., 1982) and GM2 (Natoli et al., 1986), which recognize GalNAc-bearing glycolipids. These antibodies selectively stain neuromuscular junctions, where they recognize glycolipid-like molecules that bind VVA-B4 but are distinguishable from AChE. The association of a synapse-specific carbohydrate with at least 2 different synapse-specific molecules raises the possibility that the former plays a role in determining a property that the latter share, such as concentration at the synapse. PMID- 3346731 TI - Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation. AB - In the mammalian cerebral cortex, neurons in a given layer are generated at about the same time in development. These cells also tend to share similar sets of morphological and physiological properties and have projection patterns characteristic of that layer. This correspondence between the birthday and eventual fate of a cortical neuron suggests the possibility that the commitment of a cell to a particular laminar position and set of connections may occur very early on in cortical development. The experiments described here constitute an attempt to manipulate the fates of newly generated cortical neurons upon transplantation. The first set of experiments addressed the normal development of neurons in the primary visual cortex (area 17) of the ferret. Injections of 3H thymidine into newborn ferrets showed that neurons generated after birth are destined to sit in layer 2/3 of the cortex, whereas neurons born on embryonic day (E) 32 populate primarily layers 5 and 6. Many layer 2/3 neurons in adult ferrets could be retrogradely labeled with HRP from visual cortical areas 18 and 19, while about half of the neurons in layer 6 were found to project to the lateral geniculate nucleus (LGN). In the second set of experiments, presumptive layer 2/3 cells were labeled in vivo by injecting ferrets with 3H-thymidine on P1 and P2. Before the cells had a chance to migrate, they were removed from the donor brain, incubated in a fluorescent dye (DAPI or fast blue), and dissociated into a single cell suspension. The labeled cells were then transplanted into the proliferative zone of a littermate host ferret ("isochronic" transplants). Over the next few weeks, many of these dye-labeled cells underwent changes in their position and morphology that were consistent with a radially directed migration and subsequent differentiation into cortical neurons. The final positions of isochronically transplanted neurons in the host brain were mapped out by using the 3H-thymidine marker after long survival periods. About 97% of radioactively labeled cells had migrated out into the visual cortex, where they attained a compact laminar distribution: 99% were found in layer 2/3, their normal destination. The labeled cells had normal, mostly pyramidal neuronal morphologies and appeared to be well integrated with host neurons when viewed in Nissl-stained sections. Ten isochronically transplanted neurons were successfully labeled after HRP injection into 2 normal target regions, areas 18 and 19.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346732 TI - Quinolinic acid metabolism in the rat brain. Immunohistochemical identification of 3-hydroxyanthranilic acid oxygenase and quinolinic acid phosphoribosyltransferase in the hippocampal region. AB - Quinolinic acid (QUIN) is a potent endogenous excitotoxin, which has been shown to be present in the brain (Wolfensberger et al., 1983). In order to study the cellular localization of QUIN metabolism in the hippocampus, specific antibodies raised against purified rat liver 3-hydroxyanthranilic acid oxygenase (3HAO) and quinolinic acid phosphoribosyltransferase (QPRT), the enzymes directly responsible for QUIN synthesis and catabolism, respectively, were used for immunohistochemical studies in the adult male rat. Cells containing 3HAO immunoreactivity (3HAO-i) were present in all subfields of the hippocampal region, including the area dentata, Ammon's horn, the subicular complex, and the entorhinal area. The highest density of 3HAO-i cells was found in the molecular layer of Ammon's horn and in the hilus of area dentata, while the granular cell layer of area dentata and stratum pyramidale of Ammon's horn contained the lowest number of 3HAO-stained cells. A majority of hippocampal 3HAO-i cells were also stained with monoclonal antibodies against glial fibrillary acidic protein (GFAP) or S-100 protein, suggesting that 3HAO-i is present primarily in astrocytes. At the ultrastructural level, 3HAO-i was found to be distributed uniformly throughout the cytoplasm, with intense immunostaining present in the internal and the external layers of the mitochondria. QPRT-i was detected in 3 morphologically distinct cell types present in all parts of the hippocampus. The total number of QPRT-i cells was lower than that of the 3HAO-i cells. QPRT-i cells were relatively numerous in the molecular and radial layers of Ammon's horn, while they occurred only sporadically in stratum pyramidale of Ammon's horn and in the granular cell layer of area dentata. Many QPRT-i cells stained with antibodies against GFAP and S-100, but the proportion of cells in which QPRT was colocalized with these glial marker proteins was lower than that for 3-HAO-i cells. At the ultrastructural level, 2 types of QPRT-i glial cells were detected. The smaller cell type had a diffuse cytoplasmic staining, while the larger cell type, which also contained glial filaments, showed diffuse cytoplasmic staining and intense staining of lysosomal structures. The observation that 3HAO and QPRT only partially coexist in hippocampal glial cells suggests that while synthesis and catabolism of QUIN may occur in the same glial cells, catabolism of QUIN can also take place in cells lacking the synthetic enzyme.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3346733 TI - Comparison of bone density measurements from different skeletal sites. AB - Absorptiometric measurements from multiple sites in 212 consecutive patients were examined to determine the interrelationships among bone mineral content values obtained from the lumbar spine, hip, and forearm. Dual photon absorptiometry was used to examine the spine, femoral neck, Ward's triangle, and greater trochanter while the radius and ulna were studied with single photon absorptiometry. All studies were performed on the same day. Concurrent measurements were available for the spine and hip in 197 patients, for the spine and forearm in 151 patients, and at all three sites for 146 patients. Variable degrees of correlation were found among the mineral content values from the six sites, with r values ranging from 0.40 to 0.93. The femoral neck and Ward's triangle showed the highest degree of correlation (r = 0.93); the ulna and lumbar spine demonstrated the poorest correlation (r = 0.40). Relationships between distant anatomic sites exhibited a large amount of variability (large standard error of the estimate) even when highly correlated. Useful predictions of bone mineral content could be obtained only for sites in close proximity. These results suggest that bone mineral content determinations in the upper extremities by single photon absorptiometry may not be useful for predicting mineralization in clinically more significant areas such as the lumbar spine and hip. PMID- 3346734 TI - Pre-targeted immunoscintigraphy of murine tumors with indium-111-labeled bifunctional haptens. AB - A method of tumor imaging utilizing the nonspecific accumulation of antibody through leaky capillaries is described, in which the antibody and the radiolabel are administered separately. Nonradioactive antibody is given first (pre targeted), and allowed adequate time to reach maximum tumor concentration. Depending on the antibody, this may take several days. At the time of maximum tumor concentration of nonradioactive antibody, the blood is quickly cleared of excess circulating nonradioactive antibody using a special i.v. "chase". The radiolabel then is given and imaging done in 1 to 3 hr. The use of short lived tracers (hours) to image antibodies that localize slowly (days) in-vivo is made possible by this method. PMID- 3346736 TI - Symmetric photon deficiency in the femoral heads on bone imaging: a normal variant. PMID- 3346735 TI - Accuracy of lumbar spine bone mineral content by dual photon absorptiometry. AB - The accuracy of measurement of the bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2) of the lumbar spine by dual photon absorptiometry (DPA) was estimated by means of two different spine scanners (a Nuclear Data 2100 and a Lunar Radiation DP3). The lumbar spines of 13 cadavers were used. BMC and BMD were measured in situ and on the excised vertebrae in a solution of water/ethanol; and covered with ox muscle/porcine muscle/lard. The actual mineral weight and areal density were determined after chemical maceration, fat extraction, drying to a constant weight, ashing for 24 hr at 600 degrees C, and correction for the transverse processes. The true are was measured by parallax free X rays and planimetry. All measurements of BMC or BMD were highly interrelated (r = 0.94-0.99). The standard error of estimate (s.e.e.) of BMC in situ versus BMC in water/ethanol was 5.2%. The agreement between the BMD values of the two scanners was very good (s.e.e. = 2.9%). BMC in situ predicted the actual vertebral mineral mass with an s.e.e. of 8.1%. BMD in situ and BMD in water/ethanol predicted the actual area density with s.e.e.s of 10.3% and 5.0%, respectively. This study discloses the correlation and accuracy error of spinal DPA measurements in situ in whole cadavers versus the actual BMC and BMD. The error, which is underestimated in in vitro studies, amounts to 10%. PMID- 3346737 TI - Acceptance testing of gamma cameras. PMID- 3346738 TI - Thyroid cancers in atomic bomb survivors exposed in youth: 30-year follow-up study. PMID- 3346739 TI - First-pass radionuclide angiography using a multiwire gamma camera and tantalum 178. AB - A portable multiwire gamma camera (MWGC) with enhanced imaging characteristics relative to conventional sodium iodide camera has been evaluated with 178Ta, a short-lived, generator-produced radioisotope (half-life 9.3 min). First-pass radionuclide angiography (FPRA) was performed and results were compared to those obtained with FPRA using a multicrystal camera (MCC) and 99mTc in 38 patients. The overall left ventricular count sensitivity (counts/mCi/sec/millisteradians [msr]) was significantly higher with MWGC/178Ta (176 +/- 132 versus 108 +/- 49, p less than 0.001) yielding images of higher statistics with higher resolution collimation (31 versus 63 msr). Left ventricular ejection fraction was 0.54 +/- 0.18 by MWGC and 0.54 +/- 0.18 by MCC with an excellent correlation between the two techniques (r = 0.94, s.e.e. = 0.06). The detection of wall motion abnormality was virtually identical with the two techniques. Intra- and interobserver reproducibility by MWGC was excellent (r = 0.99 and 0.99, respectively). Thus, this new technology provides first-pass studies of higher statistical quality and improved resolution, affording more precise assessment of left ventricular performance and likelihood of further substantial improvement by use of even higher doses of 178Ta. PMID- 3346740 TI - Analysis of thallium-201 "washout" from parametric color coded images. AB - We developed a parametric washout image which color codes regional washout, and blindly compared enhanced perfusion images in multiple projections with regional washout graphs and images in 25 patients. Washout images permitted true spatial and anatomic assessment of regions viewed en face as well as those seen in tangent, making possible the exclusion of non-coronary irregularities and permitting evaluation of washout over the apparent cavity. "Cavitary" washout was abnormal in 10 of 12 patients with apparent cavitary dilation on the post stress image, but in none without this finding. The distribution and rotation of washout abnormalities seen over the cavity when viewed en face, and the long delay between the termination of stress and post-exercise image acquisition, suggest that apparent cavitary dilation is often related to improved visibility of the 201T1 deficient blood pool due to relative ischemia of the overlying myocardial wall. PMID- 3346741 TI - Radionuclide imaging of the spleen with heat denatured technetium-99m RBC when the splenic reticuloendothelial system seems impaired. AB - Imaging of the spleen of 10 patients who had been hematologically diagnosed with sickle-cell anemia (SCA) was studied with [99mTc]tin colloid and heat denatured [99mTc]RBCs. In all ten patients, there was faint or nonvisualization of the spleen with [99mTc]tin colloid. However, with heat denatured [99mTc]RBCs, nine spleens were well visualized, and the uptake was homogenous. One spleen had two patchy areas of uptake. The results indicate that when splenic phagocytic function is impaired as reflected by nonvisualization of the spleen with [99mTc]tin colloid, it is still possible to image such a spleen with heat denatured [99mTc]RBCs. PMID- 3346742 TI - Clinical significance of isolated scintigraphic sternal lesions in patients with breast cancer. AB - Isolated scintigraphic sternal lesions are rare. In a retrospective review of the bone scan results of 1,104 patients with breast cancer, 34 individuals (3.1%) presented with this abnormality. Of these foci, 26 (76%) were found to represent metastatic disease. There did not appear to be a relationship with axillary lymph node metastasis, the quadrant involved by primary breast tumor, or selected serum chemistries. These sternal lesions may be associated with regional lymphatic tumor spread rather than hematogenous seeding and therefore could be considered a local recurrence. PMID- 3346743 TI - Radioimmunodetection of human melanoma with indium-111-labeled monoclonal antibody. AB - The purpose of the study was threefold: (1) to evaluate the efficacy of an 111In labeled murine monoclonal antibody (ZME-018) directed against a heavy molecular weight melanoma associated glycoprotein in localizing metastatic disease; (2) to determine the effect of unlabeled antibody mass (2.5, 5, 10, 20, and 40 mg) on labeled antibody blood clearance, biodistribution and lesion detection; (3) to estimate radiation dosimetry. Twenty-five patients with previously documented disease received an intravenous infusion of 2.5 to 40 mg of monoclonal antibody with 1 mg of the antibody labeled with 5 mCi of 111In. There were no acute reactions. Patients were scanned without computer enhancement or background subtraction techniques at 24 and 72 hr after injection. Imaging detected tumor in 14/18 (78%) patients with active disease, identified 24/44 (77%) of lesions greater than 1 cm and changed or specifically directed patient management in 22% (4/18) patients with tumor. There was a prolongation in blood clearance associated with decreased liver and spleen activity following administration of 20 and 40 mg of antibody compared to the three lower antibody dose levels. Assuming a biodistribution similar to [111In]ZME-018, the radiation dose delivered to normal tissues by [90Y]ZME-018 would restrict its use as a routine vehicle for radioimmunotherapy; however, it may be possible to deliver substantial tumor doses in selected patients. PMID- 3346744 TI - Synthesis of "no-carrier-added" alpha-[11C]methyl-L-tryptophan. AB - Described here is a synthesis of "no-carrier-added" alpha-[11C]methyl-L tryptophan based on alkylation with 11CH3I of an anion generated by reacting the Schiff base of L-tryptophan methyl ester with di-isopropylamine. The synthesis requires approximately 30 min after the end of 11CO2 collection and gives alpha [11C]methyl-L-tryptophan in a 20-25% radiochemical yield calculated at the end of the synthesis and without correction for radioactive decay. The specific activity of the final radiopharmaceutical, measured at the end of the synthesis, was around 2,000 Ci/mmol. Data confirming the stereospecificity of the synthesis are also presented. PMID- 3346745 TI - The effect of energy window on cardiac ejection fraction. AB - ECG gated gamma-ray energy spectra from the left ventricle were created each 50 msec during the cardiac cycle. Nine of ten subjects were studied with a nonimaging Nal probe, and the tenth with a high-resolution Germanium detector. Placing multiple energy windows over the energy spectra, EF was found to vary with the energy window selected. Moving a 20% window across the photopeak produced a roughly linear increase in EF with energy (2.3 EF units per 10 keV increase in energy) in eight of the ten subjects. Dividing the photopeak into a low (126-140 keV) and high-energy (140-154 keV) portion gave significantly different EFs (high energy exceeding low energy by 17%). Increasing the width of a narrow window centered about the photopeak produced negligible change in EF. Examining the energy spectra showed that the small-angle scattered radiation (126 139 keV) was proportionately greater at end systole than at end diastole, after normalizing the spectra to the same photopeak area. PMID- 3346746 TI - Human breast milk excretion of iodine-131 following diagnostic and therapeutic administration to a lactating patient with Graves' disease. AB - Previous reports on the excretion of 131I into human breast milk have recommended discontinuance of breast feeding from 1 to 12 days following diagnostic tracer doses of 131I. Recent excretion models have calculated that breast feeding could safely resume 56 days following a 5 microCi (0.185 MBq) 131I maternal tracer dose. We studied a postpartum patient with Graves' disease following first an uptake dose of 8.6 microCi (0.317 MBq) and then for 38 days following a 9.6 mCi (355 MBq) therapy dose of Na131I. We calculated from our data that although nursing could not be safely resumed for 46 days following the 8.6-microCi uptake dose, nursing could resume in this patient 8 days after a 100-nCi (3.7 KBq) dose. Extrapolating this data to impure 123I (p, 2n or p, 5n) we feel that standard 100 microCi (3.7 MBq) doses of either 123I preparation is not suitable if nursing is to be resumed. PMID- 3346747 TI - Radionuclide bone imaging findings in recurrent calvarial infarction in sickle cell disease. AB - A patient with sickle cell disease developed bi-parietal calvarial infarctions, and subsequently developed bi-frontal calvarial infarctions. The findings on [99mTc]MDP bone imaging showed decreased activity in the parietal and frontal regions during the phase of acute infarction and increased activity in the parietal region during the later healing phase. Thus the findings on radionuclide bone imaging in cortical infarcts will depend upon the stage of the condition. PMID- 3346748 TI - Xenon-133 splenoportography in Budd-Chiari syndrome. PMID- 3346749 TI - Medical treatment of radiation sickness. PMID- 3346750 TI - Managing organizational mergers. AB - Reimbursement, competition, and other significant trends in the health field have stimulated an increase in mergers among health care organizations. Mergers inevitably produce significant ramifications for clinicians. Nurses have discovered that mergers produce a greater need for efficient patient care, but not necessarily the mechanism or guidance for achieving this goal. Nursing administrators are responsible for minimizing the negative impact of a merger on nurses while simultaneously promoting merger goals. Despite this increase in mergers and the subsequent challenge to clinicians, little information is available about how to manage mergers. This article reviews the impact of the merger between the Veterans Administration Medical Center and the Kirtland Air Force Base Hospital in Albuquerque, New Mexico. A nursing perspective is used to understand what problems arise and how nursing administrators can effectively manage these problems. PMID- 3346751 TI - Research in service settings: Part II--Consortium project. AB - Part I (February 1988) of this series of two articles described the outcomes of the first 3 years of this project, which is aimed at incorporating nursing research in service settings through a consortium of health care agencies. So that nurse executives interested in employing similar strategies in their own geographic area may have a complete picture of the evolution of this collaborative approach, Part II describes the consortium's current program and its ongoing development. PMID- 3346752 TI - Attrition: the effectiveness of retention activities. AB - As the nursing shortage worsens and the ability to retain nurses becomes more difficult, hospitals are increasing their recruitment efforts. Nurses will, however, also upgrade their job expectations and seek out the best employment opportunities. What can proactive nurse administrators do to prepare for the task of retaining a stable nursing staff? The conclusions and recommendations from two studies over a 10-year period provide insight into managing the current nursing shortage. PMID- 3346753 TI - Establishing a Nursing Bioethics Committee. AB - Nursing must keep pace with the technological revolution and radical new treatment modalities of patient care, many of which cause ethical dilemmas. To address the unique ethical concerns of staff nurses and managers, the authors discuss the development, implementation, and evaluation of a Nursing Bioethics Committee. The findings of a questionnaire measuring staff nurses' perceptions of the degree of difficulty and frequency of ethical problems in clinical practice are described. The benefits of the committee are presented from the perspective of staff nurses and nurse executives. PMID- 3346754 TI - Role stress and coping strategies of nurse executives. AB - Role stress among top level nurse executives has been linked to adverse personal effects. A study was conducted to better understand role stress and to assess the coping strategies used by top level nurse executives. The author discusses four major factors--overload, quality of care concerns, role conflict, and role ambiguity--related to role stress and ten coping strategies. Awareness of these issues can help the nurse executive to understand the job stresses inherent in the role and to use constructive methods of coping with that stress. PMID- 3346755 TI - Focus paper: A method for discussing nursing issues. AB - A position paper can be one avenue or method of providing a framework for discussing nursing issues with peers, colleagues, and health care executives. A position paper/issue paper will frequently focus on one view with subsections, but can raise many other questions as well as touching on additional nursing issues. It should be clear when developing a position paper that the goal of the paper is to provide a framework for discussion--with the major emphasis being on issues being raised, not resolved. The paper should also address how nursing is affected by these issues and how the entire hospital may be affected. Last, a position paper should also articulate your--the nurse executive's--position on the issues under discussion. PMID- 3346756 TI - The influence of research funding on the organization's credibility and fiscal affairs. PMID- 3346757 TI - Participative management: a contingency approach. PMID- 3346758 TI - Practice models. PMID- 3346759 TI - Maternal-child health in Brazil. PMID- 3346760 TI - Chorionic villi sampling: a nursing perspective. AB - A relatively new procedure, chorionic villi sampling is now available as an alternative method for prenatal diagnoses of genetic disorders during pregnancy. Indications, procedures, risks, advantages, and nursing implications of this procedure are defined and described. Readers are thereby provided with current information concerning prenatal genetic diagnosis that may be passed on to patients in need of this information. PMID- 3346761 TI - Nursing management of the pregnant psychotic patient during labor and delivery. AB - Pregnant psychotic women are high-risk patients who require both psychiatric and obstetric nursing expertise. Symptoms of psychosis are described, including disorganized thinking, impaired judgment, and distorted interpretations of reality. Various ways these symptoms can interfere with the labor and delivery process are discussed. Specific principles for assessment and intervention in the care of these patients are explained including the use of psychiatric consultation, medication, and psychotherapeutic interventions. PMID- 3346762 TI - A perinatal center based antepartum homecare program. AB - Homecare for the high-risk antepartum client is a rapidly growing specialty of perinatal nursing. In a tertiary care center, a homecare component staffed by specially trained obstetric nurses with fetal monitoring expertise provides for comprehensive home visits. Home visits by nurses enable the client to remain safely in her own environment during the experience of a high-risk pregnancy. Nursing care for this population includes the provision of physical care, home fetal monitoring, education, and support throughout the pregnancy. PMID- 3346763 TI - The Teflon intravenous catheter: incidence of phlebitis and duration of catheter life in the neonatal patient. AB - The risks and benefits of intravenous therapy for neonatal patients have not been adequately evaluated. A study was conducted to assess the duration of life of the Teflon catheter used for intravenous therapy in neonates, the incidence of phlebitis associated with this catheter, and the factors which contribute to catheter life and phlebitis. Seventy-two neonates undergoing intravenous therapy with the Teflon catheter were studied. Study results indicated a mean catheter life of 30.1 hours, with 33 of the 72 catheters lasting less than 24 hours. Erythema occurred in 32 cases and phlebitis occurred in 5 cases. Of 19 predictor variables studied, low level of activity and administration of blood transfusion through the catheter were positively correlated with duration of catheter life. The Teflon catheter offers a reasonable though limited means for intravascular access in neonates. PMID- 3346764 TI - Sibling visitation: effects on newborn infection rates. AB - This study compared signs and symptoms of infection in term infants who had direct contact with their siblings with infants who had contact only with an adult visitor as part of a postpartum hospital visitation program (N = 150). Following sibling visitation, mothers assessed their infants for signs and symptoms of infection using a questionnaire designed for this study. No increase in signs and symptoms of infection associated with direct sibling visitation in this setting was identified. PMID- 3346765 TI - Initial acquaintance and attachment behavior of siblings with the newborn. AB - The attachment process of siblings to the newborn was examined. Data were collected from observations of 30 siblings during initial encounters with the newborns and interviews with parents. Sibling behaviors to the newborn fell into two overlapping categories--acquaintance and attachment. The children interacted more with their mothers than with the newborns. No attachment behaviors were seen in children with loss experience. Methods of facilitation of acquaintance were identified. PMID- 3346766 TI - Insertion and care of multiple lumen peripherally inserted central line catheters. PMID- 3346767 TI - IRA rollovers: sheltering your retirement funds from excessive taxation. PMID- 3346768 TI - Care of the cardiac patient: assessment, evaluation, and nursing implications. Part I. ECG interpretation, nursing diagnosis, and cardiac medications. PMID- 3346769 TI - Geriatric i.v. therapy. PMID- 3346770 TI - The toxic plant proteins ricin and abrin induce apoptotic changes in mammalian lymphoid tissues and intestine. PMID- 3346771 TI - Pathological Society of Great Britain and Ireland. 156th meeting. 6-8 January 1988. Synopses of papers. PMID- 3346772 TI - A quantitative study of glomerular basement membrane changes in IgA nephropathy. AB - A quantitative study of glomerular basement membrane (GBM) changes in 16 cases of IgA nephropathy was carried out on two whole glomeruli per case using a wide field electron microscope. We found that GBM changes are observed more frequently than previously reported, although some changes are small and uneven in distribution. Changes include (a) attenuation, (b) lytic attenuation, (c) garland shaped widening of the GBM, (d) dome-shaped widening of the GBM, and (e) disruption of the GBM. There was some correlation between the severity of light microscopic findings and the percentage of GBM affected by complicated changes ((b)-(e)). The percentage of complicated GBM changes correlated with the amount of proteinuria at biopsy. The frequent occurrence of GBM changes in IgA nephropathy suggests that they might be playing a role in the pathogenesis of IgA nephropathy. PMID- 3346773 TI - Ambulatory care of febrile infants younger than 2 months of age classified as being at low risk for having serious bacterial infections. AB - We prospectively examined whether febrile infants younger than 2 months of age who were defined as being at low risk for having bacterial infection could be observed as outpatients without the usual complete evaluation for sepsis and without antibiotic treatment. A total of 237 previously healthy febrile infants were seen at the Pediatric Emergency Room over 17 1/2 months. One hundred forty eight infants (63%) fulfilled the criteria for being at low risk: no physical findings consisting of soft tissue or skeletal infections, no purulent otitis media, normal urinalysis, less than 25 white blood cells per high-power field on microsopic stool examination, peripheral leukocyte count 5000 to 15,000/mm3 with less than 1500 band cells/mm3. One infant appeared too ill to be included, and had sepsis and meningitis. None of the 148 infants at low risk had bacterial infections, versus 21 of 88 (24%) of those at high risk (P less than 0.0001); eight of 88 (9%) had bacteremia. Of the 148 infants classified as being at low risk for having bacterial infection, 62 (42%) were discharged to home, and 72 (49%) were initially observed for less than or equal to 24 hours and then discharged. Seventeen infants (11%) were hospitalized: in six, low risk became high risk; six had indications other than fever; and five because the study physicians could not be found. The 137 nontreated infants were closely observed as outpatients. The duration of fever was less than 48 hours in 42%, and less than 96 hours in 91%. All infants were observed for at least 10 days after the last examination. The fever resolved spontaneously in all infants but two, with otitis media, who were treated as outpatients. Our data suggest that management of fever in selected young infants as outpatients is feasible if meticulous follow-up is provided. PMID- 3346775 TI - Patient, parent, and physician perspectives on pediatric oncology rounds. AB - To provide data to guide physicians regarding the extent to which pediatric patients and their families should be involved in decision-making discussions by their health care teams, we compared the standard rounding procedure in a pediatric oncology unit (rounds conducted out of earshot) with bedside rounds in which management was discussed in front of patients and parents. Type of rounds was alternated in 2-week blocks for 4 months. The impact of the two types of rounds of 35 parents and children was studied. Parents preferred bedside rounds to standard rounds, and perceived increased opportunities to obtain information and ask questions. Parents and children differed in their reports of how much bedside rounds upset children. Older children, compared with younger children, more strongly disliked standard rounds; this appeared to be related to feelings of exclusion. The two types of rounds differed in their effectiveness in providing specific types of education to residents. The findings suggest that bedside rounds have a positive impact on parents' attitudes toward physicians, that they do not dilute the child's sense of relationship with the primary attending physician, and that they contribute to certain aspects of resident education. PMID- 3346774 TI - Diabetes mellitus associated with cystic fibrosis. AB - The prevalence of overt diabetes mellitus and carbohydrate intolerance was studied in 448 patients with cystic fibrosis (CF). Insulin-dependent diabetes (IDDM) developed in 7.6% of patients (13 male and 21 female). Survival was significantly lower (P less than 0.01) in the IDDM-CF group, with fewer than 25% surviving to age 30 years, whereas nearly 60% of the nondiabetic CF population reached this age. A significant deterioration in CF clinical status, based on NIH score, became apparent 2 years before onset of overt IDDM (P less than 0.05 at 2 years prior, P less than 0.01 at IDDM diagnosis). Total glycosylated hemoglobin (HbA1) was significantly (P less than 0.001) higher for the total CF population (7.3% +/- 1.2%) than for the general non-CF population (6.5% +/- 0.7%), and in the IDDM-CF group (P less than 0.05) compared with normoglycemic CF control patients. Female patients had a higher mean HbA1 after 12 years of age than their male counterparts did (P less than 0.02). HBA1 did not predict the development of IDDM, but there was a weak inverse relationship between HbA1 and both NIH clinical score (r = -0.41, P less than 0.02) and standard pulmonary function tests (forced vital capacity, r = -0.25, P less than 0.01) in the general CF population. Therefore, impaired carbohydrate tolerance in CF is associated with progressive clinical deterioration. PMID- 3346776 TI - Automotive restraint systems for premature infants. AB - Automotive restraint systems suitable for use with low birth weight infants were crash tested using a small infant dummy developed for the study. Conventional semiupright rear-facing child restraints were tested, as well as a new car bed restraint that may be advantageous for infants who are medically fragile and who must remain in a prone or supine position. This car bed can be adapted to accommodate a very small infant effectively. PMID- 3346777 TI - Behavior disturbance in 8-year-old children with early treated phenylketonuria. Report from the MRC/DHSS Phenylketonuria Register. AB - Using the Rutter Behavior Questionnaire, schoolteachers assessed the frequency of common abnormal behavior in 544 8-year-old children with phenylketonuria who were born in the United Kingdom and in whom the diagnosis was made by routine testing in infancy, either during the early years of screening (cohort 1, births 1964 to 1971) or after a national reorganization of the program (cohort 2, births 1972 to 1977). All children received treatment before 4 months of age. Two matched control subjects were assessed for each patient. Compared with the controls, patients in cohorts 1 and 2 receiving a strict low-phenylalanine (phe) diet (average phe concentration less than 600 mumol/L) were 1.5 and 1.7 times, respectively, more likely to have deviant behavior; those receiving a less well controlled diet were 2.5 and 1.9 times, respectively, more likely to show such behavior. Patients more often had mannerisms, hyperactivity, and signs of anxiety and were less responsive and more solitary than were controls. On the other hand, they were not more aggressive, untruthful, or disobedient, nor absent from school more frequently. The increased frequency of deviant behavior may be the result of both psychologic stress and neurologic impairment. PMID- 3346778 TI - Secondary carnitine deficiency in hyperammonemic attacks of ornithine transcarbamylase deficiency. AB - Carnitine status was evaluated in 12 patients with hyperammonemic attacks caused by a deficiency in ornithine transcarbamylase. We found decreased free carnitine and increased acylcarnitine levels in the serum, a decreased free carnitine content and an elevated acyl/free carnitine ratio in the liver, and increased excretion of free and acylcarnitine in the urine. Analyses of urinary acylcarnitine using the secondary ion mass spectrometry technique revealed increased amounts of acetylcarnitine and dicarboxylic acid derivatives. These data suggest that the patients had a secondary carnitine deficiency, possibly an aggravating factor in urea cycle dysfunction. After oral administration of L carnitine (50 to 100 mg/kg/d) in two patients, hyperammonemic episodes were less frequent. Blood ammonia levels decreased significantly, accompanied by an increase in serum free carnitine levels. PMID- 3346779 TI - Diabetes and cystic fibrosis: new questions emerging from increased longevity. PMID- 3346780 TI - Thoughts on the training of pediatric generalists. PMID- 3346781 TI - Nosocomial bacterial pneumonia in ventilated children: clinical significance of culture-positive peripheral bronchial aspirates. PMID- 3346782 TI - Reliability of pulse oximetry in hypoxic infants. PMID- 3346783 TI - Improving reporting of tuberculin test results in a community hospital pediatric clinic. PMID- 3346784 TI - Hepatic veno-occlusive disease in newborn infant of a woman drinking herbal tea. PMID- 3346785 TI - Hyperphosphatasia with mental retardation. PMID- 3346786 TI - Decreased early diastolic function after indomethacin administration in premature infants. AB - The effect of indomethacin on systolic and diastolic cardiac function was assessed in 15 premature infants. Seven infants (group 1) received indomethacin to treat a clinically significant patent ductus arteriosus (PDA), and eight infants (group 2) received indomethacin prophylactically at 24 hours of age because of their high risk for PDA. Diastolic cardiac function was assessed using instantaneous rates of change of left ventricular (LV) cavity dimension, derived from M-mode echocardiography. The maximum velocity of lengthening of the LV cavity dimension, an index of early diastolic function, fell from 63 +/- 19 mm/sec before indomethacin to 48 +/- 16 mm/sec 1 hour after indomethacin in group 1 (P less than 0.01), with the ductus still patent and the LV chamber still dilated, and also decreased in group 2, from 52 +/- 7 mm/sec to 38 +/- 6 mm/sec (P less than 0.01). This index, when normalized for loading conditions, was decreased 1 hour after indomethacin at 12 +/- 2 sec-1 and 12 +/- 1 sec-1 for groups 1 and 2, respectively, compared with values before indomethacin of 15 +/- 3 sec-1 and 15 +/- 2 sec-1. There was no effect of indomethacin on the indices of systolic function. We conclude that indomethacin decreases early diastolic function in premature infants. PMID- 3346787 TI - Improved mineral balance in very low birth weight infants fed fortified human milk. AB - Enhanced calcium and phosphorus retention was achieved in 16 very low birth weight infants (birth weight 1117 +/- 42 g, gestation 29 +/- 0.2 weeks) fed a preparation of fortified human milk augmented with calcium lactate and monobasic and dibasic phosphate salts. Measurements of growth and macronutrient utilization were similar to those obtained in a previous study of infants fed a preparation of fortified human milk that contained lower levels of calcium and phosphorus. However, unlike the relative hypophosphatemia, hypophosphaturia, and hypercalciuria noted in the infants in our earlier study, normal serum and urine phosphorus and urine calcium values were observed in this study. Postnatal calcium and phosphorus retentions correlated significantly with respective intakes, the absorption of fat, and the retention of nitrogen. The relationships among calcium and phosphorus intake and retention predict that 160 mg/kg/d and 94 mg/kg/d, respectively, must be fed to achieve retention equivalent to intrauterine estimates. Although postnatal retention of calcium and phosphorus may be increased to levels accumulated by the fetus, technical considerations for the preparation of a formula with sufficiently high levels of calcium and phosphorus must be resolved. PMID- 3346788 TI - Bacterial colonization of plastic bulb syringes. PMID- 3346789 TI - Late onset of sepsis in infants with bowel resection in the neonatal period. PMID- 3346790 TI - Phototherapy for hyperbilirubinemia in preterm infants: green versus blue or white light. PMID- 3346791 TI - Negative pressures used for delivery room neonatal resuscitation. PMID- 3346793 TI - Gram-negative bacilli in human milk. PMID- 3346794 TI - Cyclosporine in diabetes mellitus. PMID- 3346792 TI - Metoclopramide in gastroesophageal reflux of infancy. AB - This study examined the effect of metoclopramide on lower esophageal sphincter (LES) pressure, and frequency and duration of reflux episodes in 28 children (mean age (+/- SD) 9 +/- 11 months) referred for evaluation of gastroesophageal reflux (GER). Esophageal manometry was performed before and after one intravenous dose of metoclopramide (0.125 mg/kg), and esophageal pH was monitored over a 24 hour baseline period, followed by oral metoclopramide therapy (0.125 mg/kg four times a day, for 24 hours.) During pH monitoring, patients received diet for age and were kept in the prone position with the head elevated 45 degrees while sleeping. Eight patients entered a 6-month double-blind, placebo-controlled trial of metoclopramide. Metoclopramide significantly (P = 0.04) increased end expiratory LES pressure, from 14.9 +/- 7.5 mm Hg to 18.6 +/- 6.8 mm Hg. However, there was a significant (P less than 0.05) increase in the number of reflux episodes/24 hours, and no significant change in percentage of time pH was less than 4, number of episodes lasting greater than 5 minutes, or the longest episode of reflux between the 24-hour baseline and M periods. LES pressure did not correlate well with any of these measurements (r = 0.2). In the controlled trial, the three patients receiving metoclopramide, but none of those receiving placebo, were withdrawn by their parents because of exacerbation of GER symptoms and marked irritability (P = 0.01). In the placebo group, symptoms improved in four infants, but did not change in one. The use of metoclopramide in the treatment of GER of infancy needs to be reconsidered. PMID- 3346795 TI - Sudden infant death syndrome and recurrence in subsequent siblings. PMID- 3346796 TI - Treatment of gastroesophageal reflux. PMID- 3346797 TI - Supernumerary nipples and urinary tract anomalies. PMID- 3346798 TI - Advertising and teenage smoking. PMID- 3346800 TI - Intrauterine varicella infection. PMID- 3346799 TI - Fetal varicella syndrome. PMID- 3346801 TI - Early affective antecedents of adult type A behavior. AB - The early affective, apparently temperamental antecedents of Type A behavior were investigated in a Swedish longitudinal sample (N = 149). Four clusters of Type A items (describing irritability, hurried behavior, work achievement, and competitiveness) were regressed on maternal ratings of the child's poor appetite, sleep disturbances, liveliness, anger, and shyness, collected annually from infancy to adolescence. The child's liveliness, sociability, and poor appetite during infancy and childhood were positively related to the adult Type A irritability and hurried behavior clusters, as were the mother's liveliness, orderliness, and intelligence as rated by psychologists during the child's first 6 years. The two work-involvement clusters were predicted by interactive effects among shyness, poor appetite, and anger during adolescence but were unrelated to mother attributes. Sleep disturbances were only related to competitiveness and only in late adolescence. These findings indicate that the interrelated components of adult Type A behavior have contrasting developmental histories and that temperament-related constructs are important antecedents to the adult syndrome. PMID- 3346802 TI - Children's preference for challenge: the role of perceived competence and control. AB - This research tested the hypothesis that children's perceptions of academic competence and their personal control over school-related performance affects subsequent intrinsic interest and preference for challenge in an evaluative setting. In a correlational study, children's self-reported perceptions of academic competence and personal control were found to relate positively to their intrinsic interest in schoolwork and preference for challenging school activities. A subset of this sample was exposed to varying levels of a controlling directive, and preference for challenge was assessed behaviorally during a free-choice period in which subjects were unaware that they were being observed. As predicted, the data indicated that when given the evaluative, controlling directive, children who had high perceptions of academic competence and control preferred a greater challenge than did children whose perceptions were low on these measures. No difference between groups in terms of preference for challenge was evident when no controlling directive was presented. These findings are discussed in terms of theories of intrinsic motivation and potential processes that underly these effects. PMID- 3346803 TI - Styles of coping with threat: implications for health. AB - We explored individual differences in health-seeking behavior and health status in a primary care population. Specifically, we compared high monitors (those who typically scan for threat-relevant information) with low monitors (those who typically ignore threat-relevant information), while controlling for depression. Overall, high monitors came to the physician with less severe medical problems than did low monitors. Nevertheless, high monitors reported equivalent levels of discomfort, dysfunction, and distress compared with low monitors. Furthermore, during the week following their visit, high monitors expressed less symptom improvement in both physical and psychological problems than did low monitors. Finally, high monitors demanded more tests, information, and counseling during their visit than did their low monitoring counterparts, yet desired a less active role in their own care. The theoretical and practical implications of these findings are discussed. PMID- 3346804 TI - Self-efficacy and perceived control: cognitive mediators of pain tolerance. AB - The cold-pressor task was used with 102 female undergraduates in 2 experiments to determine (a) whether self-efficacy has validity as a true causal determinant of behavior change or is a correlate of change that has already occurred and (b) how perceptions of control and self-efficacy interact to determine choice behavior, persistence, and the impact of an aversive stimulus. Results of Experiment 1 indicate that self-efficacy expectations affected performance beyond what would have been expected from past performance alone. Changes in self-efficacy expectations predicted changes in cold-pressor tolerance. These findings suggest that self-efficacy expectations can be causal determinants of behavior in an aversive situation. Results of Experiment 2 indicate that self-efficacy was separable from control and that performance was best if both high levels of perceived control and self-efficacy were present. These findings support the notion that self-efficacy expectations can mediate the desirability of providing control, in that those who benefit most from control are those who are most confident they can exercise it. PMID- 3346805 TI - Shared genes, shared experiences, and similarity of personality: data from 14,288 adult Finnish co-twins. AB - Similarities for Extraversion (E) and Neuroticism (N) scale scores from the Eysenck Personality Inventory were evaluated in 7,144 adult twin pairs, drawn from the population-based Finnish Twin Cohort, as a function of the co-twins' genetic resemblance, gender, age, and the frequency of their social interaction with each other. To separate effects of shared genes from those of shared experience, we performed hierarchical multiple regressions of double-entry data matrices. Results establish the predictive significance of both genetic and experiential influences: Genetic effects remained significant when tested after the effects of social contact were first removed; conversely, for N scores, the effects of social contact remained significant when assessed after genetic influences were first removed. These findings establish genetic variance in major dimensions of adult personality but assign a significant role to common experience as well. The first finding constructively replicates reports by others; the second challenges the widespread assumption that shared experiences have a negligible impact on sibling similarity in adult personality. PMID- 3346806 TI - Asymmetric influence in mock jury deliberation: jurors' bias for leniency. AB - Investigators have frequently noted a leniency bias in mock jury research, in which deliberation appears to induce greater leniency in criminal mock jurors. One manifestation of this bias, the asymmetry effect, suggests that proacquittal factions are more influential than proconviction factions of comparable size. A meta-analysis indicated that these asymmetry effects are reliable across a variety of experimental contexts. Experiment 1 examined the possibility that the leniency bias is restricted to the typical college-student subject population. The decisions of college-student and community mock jurors in groups beginning deliberation with equal faction sizes (viz., 2:2) were compared. The magnitude of the asymmetry effect did not differ between the two populations. We hypothesized that the asymmetry effect was caused by an asymmetric prodefendant standard of proof--the reasonable-doubt standard. In Experiment 2, subjects received either reasonable-doubt or preponderance-of-evidence instructions. After providing initial verdict preferences, some subjects deliberated in groups composed with an initial 2:2 split, whereas other subjects privately generated arguments for each verdict option. A significant asymmetry was found for groups in the reasonable doubt condition, but group verdicts were symmetrical under the preponderance-of evidence instructions. Shifts toward leniency in individual verdict preferences occurred for group members, but not for subjects who performed the argument generation task. The theoretical and applied significance of these findings is discussed. PMID- 3346807 TI - Some affective consequences of social comparison and reflection processes: the pain and pleasure of being close. AB - A self-evaluation maintenance (SEM) model of social behavior was described. According to the comparison process, when another outperforms the self on a task high in relevance to the self, the closer the other the greater the threat to self-evaluation. According to the reflection process, when another outperforms the self on a task low in relevance to the self, the closer the other the greater the promise of augmentation to self-evaluation. Affect was assumed to reflect threats and promises to self-evaluation. In three studies, subjects were given feedback about own performance and the performance of a close (friend) and distant (stranger) other on tasks that were either low in self-relevance (Study 2) or that varied in self-relevance (Studies 1 and 3). In Study 1 (N = 31), subjects' performance on simple and complex tasks after each feedback trial served as a measure of arousal. Being outperformed by a close other resulted in greater arousal than being outperformed by a distant other. In Study 2 (N = 30), evaluative ratings of words unrelated to task performance served as an indirect measure of affect. Results indicated that when relevance is low, more positive affect is associated with a friend's outperforming the self than either a friend's performing at a level equal to the self or being outperformed by a stranger. In Study 3 (N = 31), subjects received feedback while their facial expressions were monitored. Pleasantness of expression was an interactive function of relevance of task, relative performance, and closeness of comparison other. The results of all three studies were interpreted as being generally consistent with the SEM model. PMID- 3346808 TI - Goals: an approach to motivation and achievement. AB - This study tested a framework in which goals are proposed to be central determinants of achievement patterns. Learning goals, in which individuals seek to increase their competence, were predicted to promote challenge-seeking and a mastery-oriented response to failure regardless of perceived ability. Performance goals, in which individuals seek to gain favorable judgments of their competence or avoid negative judgments, were predicted to produce challenge-avoidance and learned helplessness when perceived ability was low and to promote certain forms of risk-avoidance even when perceived ability was high. Manipulations of relative goal value (learning vs. performance) and perceived ability (high vs. low) resulted in the predicted differences on measures of task choice, performance during difficulty, and spontaneous verbalizations during difficulty. Particularly striking was the way in which the performance goal-low perceived ability condition produced the same pattern of strategy deterioration, failure attribution, and negative affect found in naturally occurring learned helplessness. Implications for theories of motivation and achievement are discussed. PMID- 3346809 TI - The dark side of self- and social perception: black uniforms and aggression in professional sports. AB - Black is viewed as the color of evil and death in virtually all cultures. With this association in mind, we were interested in whether a cue as subtle as the color of a person's clothing might have a significant impact on his or her behavior. To test this possibility, we examined whether professional football and ice hockey teams that wear black uniforms are more aggressive than those that wear nonblack uniforms. An analysis of the penalty records of the National Football League and the National Hockey League indicate that teams with black uniforms in both sports ranked near the top of their leagues in penalties throughout the period of study. On those occasions when a team switched from nonblack to black uniforms, the switch was accompanied by an immediate increase in penalties. The results of two laboratory experiments indicate that this finding can be attributed to both social perception and self-perception processes -that is, to the biased judgments of referees and to the increased aggressiveness of the players themselves. Our discussion focuses on the theoretical implications of these data for an understanding of the variable, or "situated," nature of the self. PMID- 3346810 TI - A "change-of-standard" perspective on the relations among context, judgment, and memory. AB - We conducted three studies that tested a "change-of-standard" perspective on the relations among context, judgment, and recall. Each study consisted of two or three sessions held a few days apart. All subjects read about the sentencing decisions of one or two target trial judges and of six nontarget trial judges who consistently gave either higher or lower sentences than the target judge(s). Each study varied both the standard that was available when subjects initially judged the sentencing decisions of a target judge and the standard available when subjects subsequently recalled those decisions. To accomplish this, we varied the context of judgment, the timing of judgment, and the overall category norm for trial judges' sentencing decisions that was available at recall. We found that although subjects had been exposed to the same target information and had initially judged it in the same way, their recall of the information was different depending on whether and how a change-of-standard had occurred between judgment and recall. Unique predictions of the change-of-standard perspective were confirmed that could not be accounted for in terms of other types of context effects on judgment and memory. PMID- 3346811 TI - In search of reliable persuasion effects: III. The sleeper effect is dead. Long live the sleeper effect. AB - The sleeper effect in persuasion is a delayed increase in the impact of a message that is accompanied by a discounting cue. Despite a long history, the sleeper effect has been notoriously difficult to obtain or to replicate, with the exception of a pair of studies by Gruder et al. (1978). We conducted a series of 16 computer-controlled experiments and a replication of the Gruder et al. study to demonstrate that a sleeper effect can be obtained reliably when subjects (a) note the important arguments in a message, (b) receive a discounting cue after the message, and (c) rate the trustworthiness of the message communicator immediately after receiving the discounting cue. These operations are sufficiently different from those used in earlier studies to justify a new differential decay interpretation of the sleeper effect, in place of the dissociation hypothesis favored by most previous sleeper effect researchers. According to the differential decay interpretation, a sleeper effect occurs when message and discounting cue have opposite and near-equal immediate impacts that are not well-integrated in memory. The effect occurs, then, if the impact of the discounting cue decays faster than that of the message. PMID- 3346812 TI - The relationship of social power to visual displays of dominance between men and women. AB - Two studies, with undergraduate subjects, investigated how sex and situation specific power factors relate to visual behavior in mixed-sex interactions. The power variable in Study 1 was expert power, based on differential knowledge. Mixed-sex dyads were formed such that members had complementary areas of expertise. In Study 2, reward power was manipulated. Consistent with expectation states theory, both men and women high in expertise or reward power displayed high visual dominance, defined as the ratio of looking while speaking to looking while listening. Specifically, men and women high in expertise or reward power exhibited equivalent levels of looking while speaking and looking while listening. High visual dominance ratios have been associated with high social power in previous research. Both men and women low in expertise or reward power looked more while listening than while speaking, producing a relatively low visual dominance ratio. In conditions in which men and women did not possess differential expertise or reward power, visual behavior was related to sex. Men displayed visual behavior similar to their patterns in the high expertise and high reward power conditions, whereas women exhibited visual behavior similar to their patterns in the low expertise and low reward power conditions. The results demonstrate how social expectations are reflected in nonverbal power displays. PMID- 3346813 TI - Change through paradox: using self-verification to alter beliefs. AB - Past research has shown that conventional strategies of persuasion tend to be ineffective against people who are highly certain of their beliefs. To change the beliefs of such individuals, we devised a paradoxical strategy that consisted of posing superattitudinal leading questions (questions that encouraged respondents to make statements that were consistent with, but more extreme than, their own viewpoints). We expected that individuals who were high in belief certainty would resist such questions and, therefore, change their beliefs in the opposite direction. To test this reasoning, we used either a conventional or a paradoxical strategy to change people's beliefs about women's roles. As suggested by earlier research, the conventional strategy was effective in changing the beliefs of targets who were low in belief certainty only. In contrast, the paradoxical strategy was effective in changing the beliefs of targets who were high in belief certainty only. A follow-up investigation replicated this effect and indicated that paradoxical injunctions change people's positions on belief dimensions rather than their perception of the dimension itself. The implications of these findings for an understanding of the interpersonal mechanisms that generate stability and change in people's beliefs are discussed. PMID- 3346814 TI - Impulsivity and speed-accuracy tradeoffs in information processing. AB - Despite its theoretical importance for such areas of research as reflection impulsivity (Kagan, 1966), there is little evidence to support the assumption that individual differences in the personality trait of impulsivity are associated with differences in the willingness to sacrifice accuracy for speed of information processing. The present studies explored this association further. In Experiment 1, high, medium, and low impulsives (identified by self-report) performed a visual-comparison task under conditions differing in the monetary payoff for speed relative to accuracy. High impulsives were consistently faster and less accurate than other subjects. However, an analysis based on Sternberg's (1969) additive-factor method indicated that high impulsives performed at least one stage of information processing as slowly and accurately as other subjects. In Experiment 2, it was found that high impulsives were actually more accurate than low impulsives when all subjects were required to process information extremely rapidly. Experiment 3 identified the response execution stage as one that high impulsives carry out just as slowly and accurately as other individuals. The data from these experiments pose problems for a simple speed accuracy tradeoff model of impulsive cognitive functioning. PMID- 3346815 TI - Mood and the mundane: relations between daily life events and self-reported mood. AB - Daily mood ratings and corresponding diary entries were studied to determine relations between common events and two independent mood factors--Positive Affect (PA) and Negative Affect (NA)--in a sample of 18 young adults over a 3-month period. In an extension of findings from earlier interindividual studies, PA (enthusiastic, delighted vs. sluggish, drowsy) was found to be associated with a wide range of daily events, whereas fewer correlations were found between these events and NA (distressed, nervous, angry vs. calm, relaxed). The relation between high PA and reported social interactions (particularly physically active social events) was especially robust, and its effects were noted repeatedly; NA was unrelated to social activity. As hypothesized, high NA was associated with physical problems; contrary to expectations, low PA also tended to be correlated with health complaints. Overall, the results reaffirm the importance of assessing NA and PA independently and suggest that PA is an interesting and important dimension that deserves more research attention. Theoretical considerations and clinical implications are discussed. PMID- 3346816 TI - Attributions for negative life events and depression: the role of perceived control. AB - Although perceptions of control occupied a central role in the development of learned helplessness theory, recent helplessness research has not considered controllability judgments when relating attributions to depression. Supporting the importance of this construct, the research discussed in this article found evidence that judgments of control interact with other attributions in predicting depression. Specifically, in a prospective study of stress and well-being in adolescence, internal, stable, and global attributions for negative events attributed to uncontrollable causes were found to be positively related to increases in depression (as predicted by the reformulated helplessness theory), but internal and global attributions for negative events attributed to controllable causes were found to be inversely related to increases in depression. The discussion considers the implications of the findings for understanding the nature of the relation between attributions for naturally occurring life events and depression. PMID- 3346817 TI - Hypnotically induced pseudomemories--sampling their conditions among hypnotizable subjects. AB - Three studies are reported in a program of research that investigated a range of parameters affecting individual differences in the incidence of hypnotically induced pseudomemory among hypnotizable subjects. Study 1 replicated Laurence and Perry's (1983b) base rates for hypnotically induced pseudomemory response among hypnotizable subjects; in Study 2 the same response was analyzed under more strictly controlled stimulus conditions. Study 3 was an investigation of the impact of a broader range of stimulus events on response and a more sensitive test of the hypothesis that individual differences in pseudomemory effects are tied essentially to the social context of hypnosis. In all three studies, independent groups of subjects were tested who were highly responsive to hypnotic suggestion. Data indicated that the incidence of pseudomemory response was stable and consistent when stringent criteria of scoring were adopted. Also, for some subjects, real and suggested memories were maintained at one and the same time when hypnotically induced memory was examined in different test settings, suggesting that pseudomemories do not permanently overlay real experience. Overall, contextual factors appeared to play a major role among susceptible subjects in determining the nature and incidence of hypnotically induced pseudomemories. PMID- 3346818 TI - Mechanisms of corneal drug penetration. II: Ultrastructural analysis of potential pathways for drug movement. AB - Ultrastructure analysis was conducted in an effort to augment the results of classical kinetic studies. Scanning electron microscopy (SEM) allowed visual inspection of cellular junctions on corneal epithelium and endothelium. The addition of calcium-chelating agents to in vivo and in vitro mounted corneas demonstrated a concentration-dependent progressive expansion of the intercellular spaces of epithelium and endothelium, as seen by SEM. The expansion of these cellular junctions correlates with increases in permeability of the cornea to glycerol under similar conditions. The size of the intercellular space was estimated by transmission electron microscopy. Use of lanthanum as a marker of aqueous diffusional pathways demonstrated that the epithelial surface is not a totally occlusive barrier to transport of small hydrophilic compounds. Development of a method whereby an administered drug could be visualized in its actual pathway of movement through the cornea was undertaken, involving precipitation of specific compounds in the tissue with osmium tetroxide vapor. Results suggest that separate pathways of drug movement exist in the cornea for hydrophilic and hydrophobic compounds. Hydrophilic compounds were preferentially located in intercellular spaces, whereas hydrophobic compounds were associated with the lipid structures of the tissue. The results of these studies are consistent with a currently proposed 'pore' model for the penetration of drugs through the cornea. PMID- 3346819 TI - Mechanisms of corneal drug penetration. III: Modeling of molecular transport. AB - A model relating the parameters of permeability coefficient in the cornea with partition coefficient and molecular weight of the penetrating species is presented. The development of the model is unique in that it includes the availability of a "pore" pathway with the corresponding kinetic data to substantiate this premise. The "pore" pathway is applied to small hydrophilic compounds and assumes that an aqueous diffusional space is available for transport of these compounds. This is in contrast to an alternate "partitioning" mechanism which is the most probable route of transport for larger or more lipophilic entities. The model is consistent with published data from this and other laboratories. PMID- 3346820 TI - Effect of dipolar aprotic permeability enhancers on the basal stratum corneum. AB - The effect of dimethyl sulfoxide, dimethyl formamide, and dimethyl acetamide on the basal stratum corneum of excised nude mouse skin was investigated. All of these dipolar aprotic solvents caused a swelling of the basal stratum corneum cells and a disruption of the normal keratin pattern. This behavior suggests that dipolar aprotic solvents might alter the barrier properties of the basal stratum corneum cells. To test this hypothesis, the distribution of topically applied, electron-dense divalent metal ions (Hg2+ and Ni2+) was studied in excised nude mouse skin which had been perturbed by the application of dipolar aprotic solvents, and in controls which had not been so treated. In control skin membranes, Hg2+ and Ni2+ were located almost exclusively in the intercellular space of the stratum corneum. However, with the application of a dipolar aprotic solvent, Hg2+ and Ni2+ were found in the intercellular spaces and inside the basal stratum corneum cells, where they appeared to be primarily associated with the cytoplasmic filaments. Sulfide precipitation allowed for the localization of Hg2+ and Ni2+, and subsequent chemical identification by energy-dispersive X-ray microanalysis. The spatial resolution of X-ray microanalysis studies was approximately 0.5-0.75 micron. The spatial alteration in mercury and nickel precipitate distribution, which occurs when the skin is pretreated with a dipolar aprotic solvent, is consistent with the hypothesis that the pathway of Hg2+ and Ni2+ diffusion through the basal stratum corneum has also been modified. PMID- 3346821 TI - Vasopressin: a model for the study of effects of additives on the oral and rectal administration of peptide drugs. AB - We previously observed, using a relatively primitive assay, that small oral doses (on the order of 1 microgram = 1 nmol = 1000 pmol per rat) of vasopressin can produce antidiuresis in hydrated rats, and that the oral activity was enhanced by simultaneous administration of an inhibitor of intestinal proteolysis. A more sensitive semi-automated computer-linked apparatus was used to conveniently and quickly compare the antidiuretic activities of the two natural and one synthetic vasopressin peptides by several routes of administration. (The approximate dose in pmol that resulted in a 50% decrease in urine flow is indicated in square brackets.) Intravenous lysine vasopressin was used as the benchmark dose [5]. Arginine and lysine vasopressin [3500], and the synthetic analogue, 1-deamino-8-D arginine vasopressin (DDAVP) [20], were active by oral administration. The oral activities of arginine and lysine vasopressin were always enhanced by the simultaneous administration of aprotinin [1000], a natural inhibitor of trypsin; the effect of aprotinin on the oral activity of DDAVP was inconsistent. The vasopressins were more active when administered by the rectum: arginine vasopressin [20] and DDAVP [10]. The rectal activities of the peptides were increased by the absorption adjuvant, 5-methoxysalicylate (arginine vasopressin [10]; DDAVP [0.5]). The vasopressin peptides were also delivered by mouth in an impermeable coating of an azoaromatic cross-linked polymer, which is degraded by bacteria in the colon, to release the peptides in the upper colon for absorption (lysine vasopressin [525]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346822 TI - A system approach to pharmacodynamics. I: Theoretical framework. AB - A general theoretical framework is constructed for the relationship between a pharmacokinetic response r (e.g., systemic drug concentration or input rate), and an observed pharmacologic effect response E. The overall relationship may be described mathematically by E = omega(r) = omega p(omega b(omega r(r))) where omega is an operator that describes the overall relationship, and omega r, omega b, and omega p are operators that describe the contributions of components of the pharmacodynamic system. The kinetic basis for applying certain general mathematical properties such as linearity are discussed. The result is the introduction of various specific mathematical structures that may be applied to pharmacodynamic systems [e.g., E = phi t(r), E = phi t(psi r*r), E = phi p(psi p*phi b(r)), and E = phi p(psi p*phi b(psi r*r))]. PMID- 3346823 TI - Pharmacokinetics of veralipride after chronic administration in humans. AB - A pharmacokinetic study of veralipride (N-[(1-allyl-2-pyrroli dinyl)methyl]-5 sulfamoyl-o-veratramide) was performed in healthy volunteers during a chronic administration. The pharmacokinetic model based on the hypothesis of a double site for drug absorption, previously used after a single-dose oral administration, was developed to fit the data obtained after chronic administration. The empirical model used allows correct depiction of the behavior of the drug in the body, especially secondary peaks. According to the results, veralipride pharmacokinetics did not show any change upon chronic administration. PMID- 3346824 TI - Effects of food on the bioavailability of sustained-release pinacidil in humans. AB - The effects of a standard breakfast meal on the bioavailability of a sustained release tablet formulation of pinacidil [(+/-)-2-cyano-1- (4-pyridyl)-3-(1,2,2 trimethylpropyl)guanidine monohydrate) were investigated in eight healthy volunteers. Concomitant food intake resulted in significantly increased maximum measured serum pinacidil concentrations, Cmax, (172 +/- 21 versus 102 +/- 49 ng/mL, p less than 0.05), and relative bioavailability, measured as AUCo-infinity (904 +/- 189 versus 697 +/- 279 ng.h/mL, p less than 0.05). The time to maximum serum concentration (tmax) was not affected by food (2.3 +/- 1.3 versus 3.3 +/- 1.2 h, p greater than 0.05), and the terminal elimination half-life, (t1/2z) was significantly decreased (4.7 +/- 2.2 versus 2.3 +/- 0.4 h, p less than 0.05). PMID- 3346825 TI - Pharmacokinetics of ketoprofen enantiomers in healthy subjects following single and multiple doses. AB - Ketoprofen (KT; m-benzoylhydratropic acid), a 2-arylpropionic acid (2-APA) nonsteroidal anti-inflammatory drug (NSAID), is marketed and used as a racemic mixture. Although generally the activity of 2-APAs is suggested to be mainly due to the S-enantiomer, information on KT pharmacokinetics is based on measurement of total concentrations of S- and R-enantiomers. In this work, using a crossover fashion, the pharmacokinetics of KT enantiomers following single (50 mg, po) and then multiple (50 mg, q6h for 3 d) doses were delineated in eight healthy subjects. A sensitive stereospecific HPLC assay was used to measure KT enantiomers in plasma and urine, and conjugated KT enantiomers in urine. There were no significant differences between the pharmacokinetic indices calculated after single and multiple administration of KT. In plasma, small but significant differences were found between concentrations of the enantiomers (mean S:R ratios of 0.81 +/- 0.19 after single and 0.87 +/- 0.11 after repeated doses). Negligible amounts of unchanged KT enantiomers were found in urine. More than 80% of the given doses was found in urine as conjugated S- and R-KT, the predominant enantiomer being S-KT (mean S:R ratios of 1.19 +/- 0.05 after single and 1.17 +/- 0.05 after repeated doses). No significant difference between the elimination t1/2 of the enantiomers was observed. It is suggested that stereoselective conjugation followed by preferential biliary excretion of the conjugated R-KT enantiomer is responsible for the observed stereoselectivity in the pharmacokinetics of the drug. PMID- 3346826 TI - Water solubility: a critique of the solvatochromic approach. AB - The reasoning and some of the assumptions behind the solvatochromic approach to water solubility are evaluated, particularly in relation to its claims. It is shown that the contribution of the pi term is uncertain, and that it can be dropped from the correlation without substantially affecting the degree of fit. The solvatochromic method is compared with the long-standing relationship between solubility and the octanol-water partition coefficient, and it is demonstrated that the latter offers a far superior route to solubility estimation. PMID- 3346827 TI - Determination of tetracycline hydrochloride in presence of anhydrotetracycline by differential pulse polarography. AB - A differential pulse polarographic method is described for the determination of the antibiotic tetracycline HCl in the presence of its degradation product anhydrotetracycline. The method utilizes the large difference in their differential pulse polarograms at a peak potential of -1.39 V in 0.1 M phosphate buffer as the base electrolyte (pH 6.8). The assay was evaluated using synthetic mixtures and applied to the analysis of commercial tetracycline HCl samples. The results obtained with this method are in close agreement with those from the spectrophotometric absorbance ratio method. PMID- 3346828 TI - Test method for evaluation of loss of prime in metered-dose aerosols. AB - A new test method is described for assessing the loss of prime in metered-dose aerosols. Two representative metered-dose valve designs and two storage positions were used to assess the utility of this test method at three different sites. Loss of prime, defined as a valve delivery 15% below the mean, was detected in three of the four test configurations. The first significant loss of prime in this study was observed at the two-week time point for valves without drain tanks stored in the upright position. Onset of loss of prime was shown to be dependent on valve design as well as storage position, thus alternate valves or storage conditions should yield different results. This test method appeared to be reproducible over the three test sites, with a slight variation in results attributed to differences in storage conditions and agitation during sample handling. This test method intentionally excluded agitation which is in sharp contrast to the normal "shake well before use" instruction to the patient. Following one priming actuation, all of the valves returned to their mean valve delivery. PMID- 3346829 TI - Effects of ethanol on neurotransmitter release and intracellular free calcium in PC12 cells. AB - The effect of ethanol on muscarine-stimulated release of l-[3H]norepinephrine ([3H]NE) was studied using the rat pheochromocytoma cell line, PC12. At concentrations of 25 mM and above, ethanol produced a dose-dependent inhibition of muscarine-stimulated release of [3H]NE. The inhibition of muscarine-stimulated transmitter release occurred in the absence of any detectable effect of ethanol on [3H]NE uptake or on muscarinic binding to the cells. However, ethanol produced an inhibition of muscarine-stimulated elevation of intracellular free Ca++ which corresponded with the inhibition of transmitter release. At concentrations greater than 100 mM, ethanol produced an increase in the basal release of [3H]NE. Intracellular free Ca++ also was increased by ethanol concentrations greater than 100 mM. The elevation of basal transmitter release and intracellular free Ca++ by concentrations of ethanol greater than 100 mM occurred independently of the inhibition by ethanol of muscarine-stimulated elevation of intracellular free Ca++ and transmitter secretion. These results suggest that the effects of ethanol on neurotransmitter release are associated with the effects of ethanol on intracellular free Ca++. PMID- 3346830 TI - Contraction mediated by Ca++ release in circular and Ca++ influx in longitudinal intestinal muscle cells. AB - The source of Ca++ responsible for contraction was examined in muscle cells isolated separately from the circular and longitudinal muscle layers of guinea pig and human intestine. Contraction was measured by scanning micrometry and cytosolic-free Ca++ ([Ca++]i) with the fluorescent indicator, quin2. In both species, contraction induced in circular muscle cells by cholecystokinin-8 (CCK 8) and acetylcholine was not affected by withdrawal of Ca++ from the medium or addition of the Ca++ channel blocker, methoxyverapamil, whereas contraction induced by both agonists in longitudinal muscle cells and by depolarizing concentrations of K+ in both cell types was abolished. Depletion of intracellular Ca++ stores with caffeine in Ca++-free medium abolished the response in circular muscle cells. Readdition of Ca++ to the medium for 30 sec restored the response in longitudinal but not circular muscle cells. [Ca++]i, measured in guinea pig muscle cells, increased 3- to 4-fold above resting levels (circular, 70.8 +/- 8.1 nM; longitudinal, 77.4 +/- 9.7 nM) in response to all three contractile agents. The increase in [Ca++]i induced by CCK-8 and acetylcholine in circular muscle cells was not affected by withdrawal of Ca++ from the medium or addition of methoxyverapamil, whereas the response to both agonists in longitudinal muscle cells and to 20 mM K+ in both cell types was abolished. It was concluded that cells from adjacent muscle layers of the intestine mobilize Ca++ differently during agonist-induced contraction, i.e., by Ca++ release in circular and Ca++ influx in longitudinal muscle cells. PMID- 3346832 TI - Neuropeptide Y inhibits the nicotine-mediated release of catecholamines from bovine adrenal chromaffin cells. AB - The possible role of neuropeptide Y (NPY) in catecholamine secretion was studied by using bovine adrenal chromaffin cells. NPY produced a concentration-dependent inhibition of nicotine-stimulated norepinephrine and epinephrine release from bovine chromaffin cells with IC50 (concentration of NPY which inhibits 50% of maximum release of catecholamines) values of 1.8 x 10(-9) M and 1.7 x 10(-9) M, respectively. Catecholamine release induced by 56 mM KCl was not inhibited by NPY at these concentrations but was inhibited by high concentration (2 x 10(-6) M) of NPY. This inhibition was not affected by the concentration of nicotine used for catecholamine release or the presence of alpha, beta adrenergic and muscarinic antagonists. A structurally related peptide, human pancreatic polypeptide, showed a similar inhibitory effect on catecholamine release, but peptide YY or avian pancreatic polypeptide had little or no effect. N-propionyl[3H]NPY binds to a single class of saturable binding sites on bovine adrenal medulla membranes with a KD = 0.32 +/- 0.07 nM and Bmax = 63 +/- 16 fmol/mg of protein. The rank order of potency of NPY and other structurally similar peptides to displace N propionyl[3H]NPY from binding is human pancreatic polypeptide greater than or equal to NPY much greater than peptide YY greater than avian pancreatic polypeptide, and is correlated with their potency to inhibit catecholamine release. These results suggest a modulatory role for NPY through a specific NPY receptor in the secretion of catecholamine from the adrenal. PMID- 3346831 TI - Cerebral metabolic interactions between thyroid state and imipramine in the rat. AB - Local rates of cerebral glucose metabolism were determined in four groups of adult rats 4 weeks after surgery: sham-operation + saline; thyro parathyroidectomy (TX) + saline; sham-operation + imipramine; or TX + imipramine. Daily i.p. injections, imipramine at 10 mg/kg or saline at 1 ml/kg b.w., were given during the 2 weeks before the deoxyglucose experiment. TX reduced glucose utilization in the limbic, motor, endocrine and auditory systems. Imipramine reduced glucose metabolism in the median eminence, both habenular nuclei and several limbic regions including the amygdala, hippocampus and parietal cortex. Five structures showed significant interactions between TX and imipramine. In three of these regions, the supraoptic nucleus, central amygdala and lateral habenula; TX and/or imipramine individually reduced metabolism and the combined treatment raised it back to within the normal range. In the dorsal raphe, TX and imipramine tended to increase metabolism and the combined treatment resulted in a decrease to within normal range. The neurohypophysis, unaffected by TX alone, showed a significant increase in activity when TX was combined with imipramine. These data indicate, in part, that both hypothyroidism and imipramine treatment alone depress metabolism in limbic forebrain and the major limbic-brainstem relay nuclei. Combined treatment normalizes metabolism in many of these limbic pathways. Hypothetically, hypothyroidism may alter central catecholamine function in such a way that the metabolic response to imipramine is reversed or altered. PMID- 3346833 TI - Pharmacology of the allodynia in rats evoked by high dose intrathecal morphine. AB - Morphine sulfate in doses of 90 to 150 micrograms/3 microliters evoke a prominent behavioral syndrome characterized by 1) periodic bouts of spontaneous agitation during which the rat scratches and bites at the skin of the caudal dermatomes and 2) vigorous agitation, vocalization and coordinated efforts to bite and escape evoked by a light tactile stimulus applied to the flank, suggestive of a pain state (allodynia). The phenomenon is not reversed by naltrexone or is it subject to tolerance. The ordering of activity of an opioid alkaloid related agent in producing this touch-evoked agitation is: noroxymorphone-3-glucuronide, morphine 3-glucuronide, morphine-3-ethereal sulfate, dihydromorphine, noroxymorphone dihydrate, hydromorphone, dihydrocodeine tartrate, morphine sulfate, dihydroisomorphine, morphine-HCl, 6-acetylmorphine, N-normorphine-HCl and (+) morphine. The following agents were essentially without effect at the highest doses examined: 3,6-diacetylmorphine, N-normeperidine-HCl, nalorphine-HCl, alfentanil, sufentanil, naloxone, naltrexone, methadone, dextrorphan tartrate, meperidine-HCl, oxycodone, levorphanol, oxymorphone, codeine phosphate, thebaine, nalbuphine and naltrexone-3-glucuronide. The observations that the sulfated and conjugated metabolites are 10 to 50 times more potent than their unmetabolized precursor suggest the possibility that, in high concentrations certain phenanthrene opioid alkaloids with a free 3-OH position, an ether bridge and no N methyl extension will be subject to conjugation and this metabolite will alter the processing of otherwise innocuous tactile stimuli. The fact that the phenomenon appeared at least partially stereospecific may reflect upon the fact that other laboratories have shown that glucuronyl transferase may preferentially convert (-)-morphine to the 3-glucuronide and (+)-morphine to the 6-glucuronide which may be less active.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346834 TI - Transport of amantadine and rimantadine through the blood-brain barrier. AB - The unidirectional transport of amantadine and rimantadine across cerebral capillaries, the anatomical locus of the blood-brain barrier, was measured with an in situ rat brain perfusion technique. Both rimantadine and, to a lesser extent, amantadine were transported principally across the blood-brain barrier by a saturable transport system with a one-half saturation concentration of about 1.0 mM (either rimantadine or amantadine). The permeability surface area constants were 8.5 x 10(-2) sec-1 (rimantadine) and 1.1 x 10(-2) sec-1 (amantadine) with concentrations of less than 1.0 microM in the perfusate. The extraction of rimantadine and amantadine from the perfusate at low concentrations (less than 1.0 microM) was 88 and 26%, respectively, of the extraction of diazepam which is 100% extracted. Amantadine and rimantadine transport through the blood-brain barrier was significantly inhibited by weakly basic drugs (e.g., diphenhydramine) but not choline (10 mM), probenecid (1 mM) or leucine (1 mM). Inasmuch as both the pKa and percentage ionized at pH = 7.4 of rimantadine (10.4 and 99.9%, respectively) are much higher than that of amantadine (pKa = 9.0 and 97.5%, respectively), and inasmuch as rimantadine is transported into brain much more readily than amantadine, our results suggest that the carrier-mediated transport of the ionized moiety is the crucial process determining the penetration of amantadine and rimantadine through the blood-brain barrier. PMID- 3346835 TI - Mechanisms of the bacterial endotoxin-cephaloridine toxic synergy and the protective effects of saline infusion in the rabbit kidney. AB - To examine the mechanisms of the nephrotoxic synergy of bacterial cell wall lipopolysaccharide (LPS) (or endotoxin) and the cephalosporin antibiotics, we have studied: 1) the effects on mean arterial blood pressure and the clearances of inulin, p-aminohippurate and cephaloridine (Cld) of a 12%-lethal dose of Escherichia coli 0111-B4 LPS (0.05 mg/kg b.wt.i.v.), with both low and high rates of saline infusion (0.1 ml/min vs. a 7.5-ml/kg load followed by 0.4 ml/min, respectively, in approximately 2-kg rabbits); 2) the separate and combined effects of LPS and saline infusion on the concentrations of Cld in renal cortex and serum; and 3) the separate and combined effects of LPS and saline infusion on the nephrotoxicity of Cld, quantified by acute tubular necrosis scoring and serum creatinine concentrations 48 hr after treatment with 90 mg/kg of Cld i.v. and by mitochondrial respiratory toxicity, depletion of reduced glutathione and production of lipid peroxidation products in renal cortex 1 hr after treatment with 90 to 360 mg/kg of Cld i.v. The following was found: 1) the increased saline infusion (saline) largely prevented an LPS-induced fall of inulin clearance and partially prevented a fall of blood pressure and p-aminohippurate and Cld clearance; 2) as a result, saline prevented slightly elevated late serum and cortical Cld concentrations in LPS-treated animals; 3) the tubular necrosis and elevation of serum creatinine caused by Cld alone was reduced slightly and that produced by the combination of LPS plus Cld was reduced greatly by saline; 4) the comparable mitochondrial respiratory toxicity found after Cld and LPS-plus-Cld was prevented by saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346836 TI - Sustained contraction of vascular smooth muscle: calcium influx or C-kinase activation? AB - We have investigated the relative contributions of Ca++ influx and C-kinase activation to the sustained contraction of smooth muscle of rabbit aorta. In physiological salt solution (PSS), the alpha adrenergic agonist, phenylephrine (PhE), induced a rapid initial contraction followed by a maintained tonic contraction whereas the C-kinase activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), caused only a slow tonic contractile response. Both PhE- and TPA-induced contractions were accompanied by a significant increase in the unidirectional 45Ca influx. The tonic phase of PhE contraction and the slow contractile response of TPA also were reduced, but not abolished completely in Ca++-free solution containing 2 mM ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid. In addition, the relatively specific C-kinase inhibitor, H-7 [1-(5 isoquinolinesulfonyl)-2-methylpiperazine], reversibly inhibited the TPA-induced contraction in PSS and almost abolished the TPA response in Ca++-free solution. On the other hand, H-7 caused only partial inhibition (30.2% +/- 4.09, n = 5) of the PhE sustained contraction in PSS and abolished completely the residual PhE maintained response in Ca++-free solution. The H-7 inhibition of the PhE sustained contraction was reversible in both PSS and Ca++-free solution. Furthermore, TPA alone could not maintain the contractile response initiated by a high K+ depolarizing solution upon replacement of the high K+ solution by normal PSS. These findings emphasize the importance of Ca++ influx and suggest only a minor role of C-kinase in maintaining the tonic contraction of vascular smooth muscle. PMID- 3346838 TI - Phencyclidine-like discriminative stimulus effects of the stereoisomers of alpha- and beta-cyclazocine in rats. AB - Stereoisomers of alpha- and beta-cyclazocine were tested in rats trained to discriminate phencyclidine (PCP; 3.0 mg/kg i.p.) from saline in a two-lever, food reinforced, drug-discrimination procedure. (+)-Alpha-cyclazocine and both (+)- and (-)-beta-cyclazocine substituted for PCP. Neither (+/-) nor (-)-alpha cyclazocine substituted for PCP, although both compounds had potent, response rate decreasing effects. When these two drugs were tested in combination with naltrexone, rate-suppressing effects were somewhat attenuated and both then resulted in substantial PCP-lever responding. Thus, PCP-like effects in the alpha series can be masked by opiate effects. (-)-Beta-cyclazocine was the most potent compound for mimicking the PCP discriminative stimulus, being 4 to 5 times more potent than PCP itself. The (+)-isomers in both the alpha and beta series were equipotent and over 10 times less potent than PCP. Thus, both stereoisomers of beta-cyclazocine have PCP-like discriminative stimulus properties and the (-) isomer, in particular, is a very potent, selective, PCP-like compound. The stereoisomers of beta-cyclazocine have over a 50-fold potency difference for PCP like effects, evidencing greater stereoselectivity for these actions than is commonly obtained with 6,7-benzomorphans. The stereoisomers of beta-cyclazocine should prove to be useful tools for studying the PCP/sigma-like effects of opioids. PMID- 3346837 TI - Acute supersensitivity to the discriminative stimulus effects of naltrexone in pigeons. AB - The ability of acute morphine injections to augment discriminative stimulus effects and rate-decreasing effects of opioid antagonists was examined in pigeons trained to discriminate among i.m. injections of morphine (5.6 mg/kg), saline and naltrexone (10.0 mg/kg). A single injection of 10.0 or 32.0 mg/kg of morphine 24 hr before naltrexone produced 3- and 10-fold decreases, respectively, in the dose of naltrexone required for complete generalization. When morphine (10.0-100.0 mg/kg) was administered 48 hr before naltrexone, pigeons were not more sensitive to naltrexone as a discriminative stimulus but continued to be more sensitive to the rate-decreasing effects of naltrexone. Conditions that produced the largest increase in sensitivity to the discriminative stimulus effects of naltrexone (32.0 mg/kg of morphine 24 hr before the session) also increased sensitivity to the discriminative stimulus effects and rate-decreasing effects of naloxone, but did not affect the discriminative stimulus effects of diprenorphine, nalorphine or morphine. Increases in sensitivity to the discriminative stimulus effects of naltrexone and naloxone after single injections of morphine approached in magnitude the increases reported previously in pigeons treated chronically (once/daily) with large doses of morphine. However, the lack of generalization to naltrexone after pretreatment with still larger doses of morphine, as well as the failure of nalorphine and diprenorphine to substitute for naltrexone as discriminative stimuli under conditions in which sensitivity to naltrexone was increased, support the view that naltrexone does not produce its discriminative stimulus effects in nondependent animals exclusively through an opioid antagonistic action. The results suggest that morphine induced, acute supersensitivity to the discriminative stimulus effects of naltrexone differs from the supersensitivity to antagonists observed during chronic morphine treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346839 TI - Characterization of muscarinic cholinergic receptor subtypes in human peripheral lung. AB - The authors have characterized the muscarinic cholinergic receptor subtypes in human peripheral lung membranes using the selective muscarinic antagonist [3H]pirenzepine [( 3H]PZ) and the classical muscarinic antagonist [3H](-) quinuclidinyl benzilate. High-affinity binding with pharmacologic specificity was demonstrated for both radioligands. The high affinity Kd for [3H]PZ binding determined from saturation isotherms was 5.6 nM, and the Kd for [3H](-) quinuclidinyl benzilate binding was 14.3 pM. Approximately 62% of the total muscarinic binding sites in human peripheral lung bind [3H]PZ with high affinity. There was no significant effect of the guanine nucleotide, guanyl-5'-yl imidodiphosphate, on the inhibition of [3H](-)-quinyclidinyl benzilate binding by the muscarinic agonist carbachol in peripheral lung membranes. If the muscarinic receptor with high affinity for PZ has an important role in bronchoconstriction, its characterization could result in the development of more selective bronchodilators. PMID- 3346840 TI - Effects of central administration of morphine on renal function in conscious rats. AB - Systemic administration of morphine in rats produces an anti-natriuretic effect that is at least partially dependent on renal nerves. The present studies were carried out in order to assess the renal response to central administration of morphine. Male Sprague-Dawley rats were surgically prepared with arterial, venous and bladder cannulas. In addition, a guide cannula was placed into the lateral ventrical and secured to the surface of the skull. Experiments were carried out at least 3 days after surgery. Renal clearance measurements were 30 min each. After a basal period, morphine sulfate (4 micrograms/4 microliters) or vehicle was injected into the lateral cerebral ventricle. Two clearance measurements were obtained, followed by central administration of naloxone HCl (4 micrograms/4 microliters) or vehicle and two more clearance periods. Morphine administration had no effect on blood pressure or heart rate but caused a sharp reduction in sodium excretion (3200 +/- 958 vs 970 +/- 158 nEq/100 g/min in period 5; P less than .05). This response was reversed by the addition of naloxone (3280 +/- 583 nEq/100 g/min in period 5; P less than .05). Furthermore, morphine had no effect on renal plasma flow and glomerular filtration rate. Naloxone increased the renal plasma flow and glomerular filtration rate in morphine-treated rats, whereas it had no effect in controls. It is concluded that central administration of morphine in conscious rats enhances renal tubular sodium reabsorption by an opiate receptor-dependent mechanism. PMID- 3346841 TI - Enterohepatic circulation of lorazepam and acetaminophen conjugates in ponies. AB - Adult female ponies (130-225 kg) with chronically implanted external biliary fistulas (T-tubes) participated in three-way cross-over studies using either i.v. lorazepam (10 mg) or acetaminophen (2 g), two model drugs biotransformed mainly by hepatic conjugative reactions. The objectives were to determine the systemic pharmacokinetics, urinary and biliary excretion and degree of enterohepatic circulation (EHC) of these compounds. Trial conditions were: A: EHC intact, with blood and urine, but not bile, collected after i.v. drug administration; B: EHC interrupted, with blood, urine and bile collected after i.v. drug administration; and C: bile infused, EHC open, without i.v. drug administration, with bile collected from trial B (containing biliary excreted drug) infused into the duodenum via the T-tube, followed by collection of blood, urine and bile. At least 2 weeks elapsed between trials. Interruption of the EHC caused lorazepam plasma half-life to shorten (3.4 vs. 2.3 hr with the EHC intact, P less than .1), clearance to increase (9.2 vs. 12.3 ml/min/kg, P less than .1) and total area under the plasma concentration curve for lorazepam glucuronide to decrease (210 vs. 310 ng/ml X hr, P less than .06). Recovery of lorazepam as its glucuronide in bile was 24.5% of the i.v. injected dose. Urinary elimination of lorazepam glucuronide was reduced from 41 to 36% of the dose due to bile collection. Subsequent duodenal infusion of collected bile, containing an average of 2.45 mg of lorazepam as glucuronide, was followed by urinary excretion of 0.48 mg of lorazepam as glucuronide in urine and 0.36 mg re-excreted into bile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346842 TI - Effect of hyperfiltration, proteinuria and diabetes mellitus on the uptake kinetics of gentamicin in the kidney cortex of rats. AB - The influence of hyperfiltration-hypertrophy, proteinuria and glucosuria on the renal cortical uptake of gentamicin was studied in several experimental models. Two groups of remnant kidney rats, one fed a standard protein diet and one a low protein diet, heavy proteinuric rats (adriamycin) and diabetic rats, each with their own control group, were treated with increasing doses of gentamicin, given as a continuous infusion over 6 hr. The relationship between increasing steady state serum levels (ranged from 1 to 100 micrograms/ml) and the cortical gentamicin concentrations at the end of the infusions was examined by means of Michaelis-Menten kinetics. The uptake curves were compared to their respective control curves. It was demonstrated that gentamicin uptake was reduced in remnant kidney rats fed standard diet (showing hyperfiltration and heavy proteinuria), in adriamycin rats (showing heavy proteinuria in the absence of hyperfiltration) and in diabetic rats. Uptake of gentamicin in remnant kidney rats fed low protein diet (showing hyperfiltration and slight proteinuria) was comparable to controls. It appeared that among the pathophysiological factors examined, proteinuria is the most important in decreasing the cortical uptake of gentamicin. It is suggested that high levels of proteins in the proximal tubular fluid interfere with the adsorptive endocytic process, involved in the uptake of both proteins and gentamicin. PMID- 3346843 TI - Synthesis and in vitro toxicity of hydroxylamine metabolites of sulfonamides. AB - Among the most serious side effects of sulfonamides are hypersensitivity reactions, the pathogenesis of which has been suggested to be mediated by reactive metabolites. We have previously demonstrated dose-related covalent binding and toxicity of reactive intermediates of sulfonamides generated by a murine hepatic microsomal activating system. We hypothesized that hydroxylamine (H/A) metabolites might be likely candidates for mediating such toxicity; accordingly, we synthesized chemically the H/As of sulfadiazine and sulfamethoxazole. Synthesis was performed using 4-nitrobenzenesulfonyl chloride and either 2-aminopyrimidine or 3-amino-5-methylisoxazole, respectively, as starting materials. The resulting nitro derivatives were reduced to the corresponding H/A with hydrogen in the presence of a poisoned platinum catalyst. After synthesis and purification, toxicity of the H/As to lymphocytes of normal volunteers was evaluated using three cytotoxicity assays: 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyl tetrazolium bromide dye conversion, trypan blue dye exclusion and propidium iodide dye exclusion. The H/As of sulfadiazine and sulfamethoxazole displayed dose-related toxicity. 1.6 mM sulfadiazine H/A produced 82% cell death, whereas 400 microM sulfamethoxazole H/A produced 62% cell death; the parent sulfonamides were not toxic to cells. The toxicity of sulfamethoxazole H/A was decreased by coincubation with glutathione or N-acetylcysteine; there was a 47% decrease in toxicity when coincubated with 100 microM glutathione, whereas there was a 55% decrease displayed when coincubation was done with 500 microM N acetylcysteine. H/A metabolites of the sulfonamides or their nitroso derivatives, normally detoxified by conjugation to glutathione, may be the proximate toxins mediating sulfonamide hypersensitivity. PMID- 3346844 TI - Pharmacokinetic drug interactions between triamterene and ranitidine in humans: alterations in renal and hepatic clearances and gastrointestinal absorption. AB - Ranitidine reduces the renal tubular secretion of the organic cations procainamide and N-acetylprocainamide in humans through competition for transport via the organic cation transport system. Ranitidine is thought to spare phase I hepatic metabolism mediated by cytochrome P-450, unlike its counterpart H2 receptor antagonist cimetidine. The aim of the present study was to determine, in eight human subjects, the effect of ranitidine on the disposition of the potassium-sparing diuretic triamterene, which undergoes renal tubular secretion, hepatic hydroxylation and subsequent sulphate conjugation to a pharmacologically active metabolite. Multiple blood and urine samples were collected throughout a dosing interval after chronic administration of triamterene alone, ranitidine alone or the two in combination. Ranitidine significantly (P less than .05) reduced the renal clearances of triamterene (51%) and p-hydroxytriamterene sulphate conjugate (47%), the clearance by hydroxylation of triamterene (30%) and the apparent absorption of triamterene (52%). In turn, triamterene reduced the renal clearance of ranitidine (14%). The interaction resulted in a small attenuation of the pharmacodynamic response to triamterene. These results necessitate consideration of the underlying mechanisms of the interactions and fall outside of our present understanding of the renal clearance of sulphate conjugates and the metabolic inhibitory effects of ranitidine. Competition for translocation across membranes is postulated as a common mechanism for the observed renal and hepatic interactions. PMID- 3346846 TI - Autoradiographic visualization of muscarinic receptors in human bronchi. AB - To visualize muscarinic receptors in human bronchi, the stripping film method was used which permits direct autoradiographic localization of tissue labeling. Cryostate sections of human bronchi were fixed in 0.5% glutaraldehyde in Krebs Ringer buffer, pH 7.0 for 30 min at 0 degrees C, washed in Krebs-Ringer buffer for 20 min at 0 degrees C and incubated with (-)-[3H]Quinuclidinyl benzilate [(-) [3H]QNB] for 90 min at 37 degrees C. Specific (-)-[3H]QNB binding to tissue sections was saturable (receptor density of 0.14 +/- 0.03 fmol/tissue section) and of high affinity (Kd of 40 +/- 9 pM). For autoradiography, labeled tissue sections were covered with stripping film and exposed for 5 months. Muscarinic receptors in human bronchi were located predominantly in submucosal glands and parasympathetic ganglia. There was less labeling in smooth muscle cells and nerve bundles. Epithelium and blood vessels located within the bronchial wall were devoid of specific labeling. PMID- 3346845 TI - Influence of blood components on the tissue uptake indices of cyclosporin in rats. AB - The effect of blood components on the transfer of cyclosporin into brain, salivary gland, liver and kidney was measured in rats by an an vivo double isotope, tissue-sampling single injection technique. The brain-, salivary gland- and liver extraction of [3H] cyclosporine relative to [14C]butanol were studied with an intracarotid and a portal vein injection technique; the kidney extraction of [3H]cyclosporin relative to p[14C]aminohippuric acid was measured after a rapid injection in the aorta. The injection vehicles were a Ringer's solution [Ringer-4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid], rat plasma, human plasma, human red blood cells (RBC) suspension and human blood. The brain extraction (1-4%), the salivary extraction (25-74%) and the kidney extraction (8 47%) varied markedly depending on which blood components were added to the injection solution. The effect of RBC binding on tissue extraction was by far more pronounced than that of plasma protein binding. The binding of cyclosporin to RBC retards particularly the uptake of this drug by kidney. Moreover the kidney penetration of cyclosporin was confirmed by thaw-mount autoradiography after injection of the labeled drug in the aorta; the micrographs showed that the renal clearance of cyclosporin was restricted largely to the glomerular route. In contrast the hepatic extraction of [3H]cyclosporin was high (48-84%) and generally nonlimited by its binding to blood components; this could explain the high concentrations of drug observed in this tissue. In summary, cyclosporin binding to RBC and plasma proteins reduces drug uptake by brain, kidney and salivary gland, but causes little inhibition of hepatic uptake of cyclosporin. PMID- 3346847 TI - Amiodarone pulmonary toxicity: biochemical evidence for a cellular phospholipidosis in the bronchoalveolar lavage of human subjects. AB - Amiodarone pulmonary toxicity represents an example of a life-threatening adverse drug reaction. Our study examined 10 subjects with amiodarone pulmonary toxicity by bronchoalveolar lavage (BAL) and determined that cells obtained by BAL demonstrated marked increases in various phospholipids compared to control subjects (n = 7). Bis monoacylglycerol phosphate and phosphatidylglycerol were significantly increased in both relative and absolute amounts (P less than .01). Several other phospholipids also were significantly increased in absolute amounts within the cell fraction. In contrast, the cell-free BAL fluid revealed only minor differences in phospholipid content. There was a strong direct correlation between concentration of amiodarone and its primary metabolite, desethylamiodarone in BAL cells (r = 0.98), and also a direct correlation between either the concentration of amiodarone or desethylamiodarone and the accumulation of phospholipids in the cells (r = 0.97, both determinations). This study indicates that findings from BAL in human subjects may provide specific and quantifiable evidence of pulmonary phospholipidosis, and suggests the concentration of the drug or its primary metabolite in BAL cells is a major determinant for the degree of phospholipid accumulation in the lung. PMID- 3346848 TI - Membrane actions of quinidine sulfate in the rabbit atrioventricular node studied by voltage clamp method. AB - The effects of quinidine (0.01-20 micrograms/ml) on spontaneous action potentials and membrane current systems of the rabbit atrioventricular node were studied. At therapeutic concentrations, this drug decreased the action potential amplitude, the maximal diastolic potential, the threshold potential as well as the maximal rate of depolarization and showed a negative chronotropic action. Quinidine, at 5 micrograms/ml, decreased the peak slow inward current by 30.2%, increased its time constant of inactivation by 27.3%, shifted the steady-state inactivation curve toward more negative membrane potentials by 2.8 mV and decreased its fully activated current. Quinidine exerted not only resting but also use-dependent blocking actions on the slow inward current. The depression of the action potential upstroke can thus be explained by the reduction in this current. The outward K+ tail current was decreased by 65.4% and its deactivation time constant was increased by 19.0%. These effects may have contributed to the prolongation of the action potential duration, the reduction in the maximal diastolic potential and the slowing of diastolic depolarization. Quinidine shifted the steady-state activation curve for this K+ current toward hyperpolarization by as much as 7.8 mV. It decreased the hyperpolarization-activated inward current by 16.3% and increased its activation time constant by 10.1%, but this current appeared to play a small role in reducing the rate of diastolic depolarization. These observations indicate that, depending upon dose, quinidine has the potential to decrease all of the time- and voltage-dependent ionic currents in atrioventricular nodal cells. PMID- 3346849 TI - Escaping borderline stereotypes. Working through the maze of staff-patient interactions. PMID- 3346850 TI - Distance in nurse-patient encounters. PMID- 3346852 TI - Response to patient assault. A peer support program for nurses. PMID- 3346851 TI - Family violence. Development of a master's level specialty track in family abuse. AB - Family violence is a societal reality. It will not disappear if society closes its eyes and fails to recognize its existence. When this is done, the abusive cycle is perpetuated. The specialty track described in this article was the nation's first graduate nursing educational program in the area of Family Violence. This program demonstrates nursing's potential contribution to the development of competent professionals with the expertise necessary to intervene in the abusive cycle. PMID- 3346853 TI - Primary facial lymphoedema with xanthomas. PMID- 3346854 TI - A stiff man with malabsorption. PMID- 3346856 TI - Benign thoracic pain. PMID- 3346857 TI - Intractable trigeminal neuralgia. PMID- 3346855 TI - Negation of responsibility: a heavy price to pay? PMID- 3346858 TI - Selling screening. PMID- 3346859 TI - Is the sudden infant death syndrome preventable? PMID- 3346860 TI - The urological Damocles. PMID- 3346861 TI - Screening for cervical cancer: review of administrative arrangements. AB - In 1980 a working party was established in Cambridge Health District to review the administrative arrangements for cervical cytology recall using the National Health Service Central Register at Southport. As a result of a number of surveys and ad hoc enquiries it was decided not to continue with the central recall scheme (which was subsequently withdrawn) and not to replace it with any formal centralized local scheme. The decision was based on the apparent failure of the central scheme, the effectiveness of informal systems already in operation locally, and the need to place cervical cancer amongst competing priorities for prevention. PMID- 3346862 TI - General practitioner referral of patients with lower gastrointestinal symptoms. AB - Of 500 consecutive patients with symptoms of colorectal disease referred to a specialist hospital for outpatient assessment, 305 were studied. There was a low incidence of examination by the general practitioner; less than half the patients had a rectal examination and 31% had no examination at all. In cases where GPs made a diagnosis, this was correct in half, which both demonstrates the potential for dangerous misdiagnosis and confirms the fact that many anorectal conditions can be identified by the history alone. It is suggested that direct-access clinics in a colorectal unit would minimize delay in accurate diagnosis. The resource implications for such a system would be limited in terms of special investigations and additional clinic facilities. PMID- 3346863 TI - Smoking--a major cause of polycythaemia. AB - The importance of smoking in the aetiology of polycythaemia has been assessed in a group of patients referred to a general haematology clinic. All patients with true and relative polycythaemia (excluding those with polycythaemia rubra vera) were studied. Of the 21 such patients evaluated, 14 were smokers and had raised carboxyhaemoglobin levels and had no other demonstrable cause for their polycythaemia. The commonest physiological abnormality in these patients was a raised red cell mass combined with a low plasma volume. Six of the 14 patients were able to reduce their smoking with subsequent improvement in their haematocrits. These results suggest that smoking is a major cause of polycythaemia in an unselected series of referrals to a general haematology clinic. The early identification of these patients may be useful in planning therapy. PMID- 3346865 TI - Are we using the correct dose of metronidazole in colorectal surgery? AB - In a series of 20 patients undergoing elective colorectal surgery, 10 received an infusion of metronidazole 500 mg and 10 an infusion of 1500 mg commencing at the induction of anaesthesia. The concentrations of metronidazole in the plasma, rectus muscle and colon of the two groups during the course of the operation were compared. In those patients who received 1500 mg, the plasma and tissue concentrations were all well above the minimum inhibitory concentration (MIC) of metronidazole against Bacteroides fragilis. In those patients who received 500 mg, serum and tissue concentrations were at or only just above the MIC. It may be that 1500 mg would be a more effective dose of metronidazole for prophylactic use in colorectal surgery. PMID- 3346864 TI - Perforated duodenal ulcer and cigarette smoking. AB - Whilst the association between smoking and peptic ulceration has been reported previously, the relationship between smoking and the complications of ulcers, such as perforation, bleeding or acute painful exacerbation, has not been examined. In a retrospective study comparing 275 emergency admissions for peptic ulcer with 275 controls, cigarette smoking was significantly more common only in those with a perforated duodenal ulcer. Of 128 patients with perforated duodenal ulcers, 110 (86%) were cigarette smokers compared with 65 (51%) of the 128 matched controls (X2, P less than 0.01). Cigarette smoking in patients with bleeding or acutely exacerbated ulcers was not significantly more common than in controls. These findings strongly suggest a particular association between smoking and perforated duodenal ulcer. PMID- 3346866 TI - Assessment of self-poisoning patients by psychiatrists and junior medical staff. AB - Case notes of patients admitted to hospital or seen in the casualty department following an overdose were assessed in a standardized way. The medical records were deficient in several important areas, especially for those patients seen in casualty and not referred to a psychiatrist. If only selected patients were to be assessed by psychiatrists, closer monitoring of the psychiatric assessments and management initiated by junior medical staff would be required. Although the poor records may reflect lack of motivation as much as lack of education, there was no significant relationship between the doctors' attitudes towards self-poisoning patients in general and the standard of their assessments. PMID- 3346867 TI - Acetohydroxamic acids as potent, selective, orally active 5-lipoxygenase inhibitors. PMID- 3346868 TI - 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl) derivatives of adenine and 3 deazaadenine: potent inhibitors of bovine liver S-adenosylhomocysteine hydrolase. PMID- 3346869 TI - 7-substituted 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3- quinolinecarboxylic acids: synthesis and biological activity of a new class of quinolone antibacterials. PMID- 3346870 TI - Synthesis and biological characterization of pyridohomotropanes. Structure activity relationships of conformationally restricted nicotinoids. AB - The recently discovered nicotinic agonist pyrido[3,4-b]norhomotropane [corrected] (PHT) as well as its N-methyl and 2'-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin a in a series of in vitro and in vivo assays. The results reveal that PHT possesses activity comparable to that of the highly potent agonist, anatoxin a. The inactivity observed relative to PHT of N-methyl- and 2'-methyl-PHT has helped to further define the structure-activity requirements of conformationally restricted nicotinoids. PMID- 3346871 TI - Effects of D-amino acid substitution on antagonist activities of angiotensin II analogues. AB - The synthesis and biological activities of angiotensin II (AII) analogues are described and compared to the literature. D-Amino acid substitution was employed to search for novel AII antagonists that would also display reduced partial agonist activity. Substitution of D-amino acids into the interior positions 2-7 of [Sar1,Ile8]-AII gave rise to inactive compounds or weak antagonists. Substitution of D-amino acids into position 8 gave rise to potent antagonists in vivo including [Sar1,D-Phe8]-AII 8, [Sar1,D-(alpha Me)Phe8]-AII (35), [Sar1,D Trp8]-AII (32), [Sar1,D-Phg8]-AII (29), [Sar1,D-Peg8]-AII (30), and [Sar1,D-Phe8] AII-NH2 (31). The structural requirements for D-AA8 analogues (antagonists) showed similarities with those of L-AA8 analogues (agonists). The latter three analogues, 29-31, were considerably more potent in vivo than their in vitro affinities would indicate, suggesting that these analogues may resist carboxypeptidase-like degradation. While partial agonist activity was not removed by D-AA8 substitution, [Sar1,D-Phe8]-AII-NH2 (31) displays lower partial agonist activity than [Sar1,Ile8]-AII. A receptor model is presented that highlights the difference between [L-AA8]-AII analogue agonist activity and [D-AA8]-AII analogue antagonist activity. PMID- 3346872 TI - Analogues of [(triethylsilyl)ethynyl]estradiol as potential antifertility agents. AB - Various 17 alpha-ethynylsteroids were prepared and derivatized as the corresponding triethylsilyl compounds 2-35, which were examined for a ratio of antifertility to estrogenic activity that would be more beneficial than that of the presently used agent. Among the triethylsilyl compounds evaluated, only 23 displayed this desired ratio, although two other compounds without the triethylsilyl moiety, 18 and 26, shared similar characteristics. PMID- 3346873 TI - Derivatives of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2 butynyl)acetamide. AB - A series of tertiary and quaternary analogues (acyclic imides, sulfonimides, N acetyl sulfonamides, and trifluoroacetamides) of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5,35) was synthesized. The compounds were found to be muscarinic agonists, partial agonists, or antagonists in the isolated guinea pig ileum. Replacement of the acetyl group or the N-methyl group of 35 and its analogues by a methanesulfonyl group abolished efficacy and decreased affinity at ileal muscarinic receptors. Trifluoroacetamide analogues of 35 also had lower affinity and efficacy than 35. Substitution of an acetyl group for the N-methyl group in compounds related to 35 decreased efficacy, but had no appreciable effect on affinity. Most of the tertiary amines showed central antimuscarinic activity as they antagonized oxotremorine-induced tremors in mice. PMID- 3346874 TI - One- and two-dimensional 1H NMR, fluorescence, and molecular modeling studies on the tomaymycin-d(ATGCAT)2 adduct. Evidence for two covalent adducts with opposite orientations and stereochemistries at the covalent linkage site. AB - Tomaymycin is a member of the pyrrolo[1,4]benzodiazepine antitumor-antibiotic group that binds covalently to the exocyclic 2-amino group of guanine in DNA. Previous correlation of fluorescence and NMR data suggested that the 11R,11aS and the 11S,11aS diastereomers of tomaymycin could bind to DNA in two orientations relative to the covalently modified guanine (Barkley, M. D.; Cheatham, S.; Thurston, D. E.; Hurley, L. H. Biochemistry 1986, 25, 3021-3031). We now report on fluorescence, one- and two-dimensional proton NMR, and molecular modeling studies of the tomaymycin-d(ATGCAT)2 adduct, which corroborate these earlier observations. Fluorescence measurements show that there are two species of tomaymycin bound to d(ATGCAT)2, which are tentatively identified as the 11R,11aS and 11S,11aS diastereomers. Two distinct sets of signals for the tomaymycin molecule are present in the proton NMR spectrum of the tomaymycin-d(ATGCAT)2 duplex adduct. Two-dimensional correlation spectroscopy (2D-COSY) studies also show connectivities for four cytosine H5-H6 and eight thymine methyl-H6 protons and thus clearly establish the presence of two distinct species of tomaymycin d(ATGCAT)2 adducts in solution. A single scalar 11-11a 1H NMR coupling in the 2D COSY spectrum is indicative of an adduct species that has an S configuration at the C-11 position. Two-dimensional nuclear Overhauser effect (NOESY) spectra of the tomaymycin-d(ATGCAT)2 duplex adduct show that the adducts are relatively nondistortive. In a NOESY experiment, cross-peaks were identified between both the aromatic H9 proton and the ethylidine methyl protons of tomaymycin and two different adenine H2 protons of d(ATGCAT)2. Molecular mechanics calculations with AMBER show that the two species with the thermodynamically most favorable binding energies are the 11R,11aS and 11S,11aS isomers with their aromatic rings to the 5' and 3' sides of the covalently bound guanine, respectively. The NOEs observed between tomaymycin protons and adenine H2 protons are in accord with molecular modeling studies. Taken together, these results strongly suggest that the two forms of tomaymycin bound to d(ATGCAT)2 are the 11S,11aS and 11R,11aS species, oriented with their aromatic rings to the 3' and 5' sides, respectively, of the covalently modified guanines. PMID- 3346876 TI - Synthesis of arginine-vasopressins, modified in positions 1 and 2, as antagonists of the vasopressor response to the parent hormone. AB - In an attempt to determine some of the structural features in position 1 that account for antivasopressor activity, eight new 1-(beta, beta-dialkyl substituted) analogues of 1-(3-mercaptopropanoic acid)-8-arginine-vasopressin and 1-(3-mercaptopropanoic acid)-2-O-methyltyrosine-8-arginine-vasopressin have been designed and synthesized. The protected precursors required for these peptides were obtained by a combination of solid-phase and solutions methods. Some of the reported analogues, namely 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8 arginine-vasopressin, 1-(1-mercapto-4-methylcyclohexaneacetic acid)-2-O methyltryosine-8-arginine-vasopressin, 1-(4-tert-butyl-1 mercaptocyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine- vasopressin, 1-(1 mercapto-4-phenylcyclohexaneacetic acid)-8-arginine-vasopressin and 1-(1-mercapto 4-phenylcyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine- vasopressin, are among the most potent and selective antagonists of the vasopressor response to arginine-vasopressin reported to date. PMID- 3346875 TI - Stereoelectronic factors influencing the biological activity and DNA interaction of synthetic antitumor agents modeled on CC-1065. AB - The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effective than 1 against murine tumors. In particular, compound 27 exhibits high activity and potency. Structure-activity analysis supports a molecular mechanism for biological action involving hydrophobic interaction of the drug with DNA and acid-catalyzed alkylation of DNA. PMID- 3346877 TI - 6-(Alkylamino)-9-benzyl-9H-purines. A new class of anticonvulsant agents. AB - Several 9-alkyl-6-substituted-purines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats. Most compounds were prepared in three steps from 5-amino-4,6 dichloropyrimidine or in two steps via alkylation of 6-chloropurine. Potent anticonvulsant activity against MES resided in compounds that contain a benzyl substituent at the 9-position of 6-(methylamino)- or 6-(dimethyl-amino)purine. Among commonly used agents for control of seizures, this type of structure represents a new class of potent anticonvulsant agents. PMID- 3346878 TI - 8-Aryl-and 8-cycloalkyl-1,3-dipropylxanthines: further potent and selective antagonists for A1-adenosine receptors. AB - A series of 1,3-dipropylxanthines were prepared with a variety of substituents at the 8-position. These included 8-aryl and 8-cycloalkyl groups. Polar carboxylate and carboxamide moieties were introduced as aryl substituents to increase water solubility. 1,3-Dipropyl-8-[2-hydroxy-4-[(carboxymethyl)oxy]phenyl]xanthine provided a functionalized congener with high potency (Ki = 37 nM) and selectivity (54-fold) for A1-adenosine receptors. This congener was used for preparation of a series of other analogues, some with higher potency and some with higher selectivity. 8-Cyclopentyl- and 8-cyclohexyl-1,3-dipropylxanthines were both very potent (Ki = 1-1.5 nM) and selective for A1 receptors, while 8-cycloalkylmethyl analogues were 10-fold less potent, but still very selective for A1 receptors. 8 Piperidinyl and 8-pyrazinyl analogues had very low activities as adenosine receptor antagonists. PMID- 3346880 TI - Regio- and stereochemical studies on the alpha-carbon oxidation of (S)-nicotine by cytochrome P-450 model systems. AB - Results from previous studies indicate that rabbit liver microsomal cytochrome P 450 catalyzes the C-5' two-electron oxidation of (S)-nicotine stereoselectivity with preferential loss of the pro-(E)-hydrogen atom trans to the pyridine ring. We now have examined the regio- and stereochemical features of the oxidation of (S)-nicotine by peroxides in the presence of various hemoproteins and by electrochemical and photochemical methods. None of these systems gave rise to the stereochemical outcomes observed with the cytochrome P-450 mediated reaction. The results of these studies are interpreted as additional evidence for the formation of a highly ordered complex between (S)-nicotine and cytochrome P-450 that directs the regio- and diasterioselective alpha-carbon oxidation of this substrate. PMID- 3346879 TI - 2-Ethynylbenzenealkanamines. A new class of calcium entry blockers. AB - A series of 2-(aryl- or alkylethynyl)benzenealkanamines were synthesized. They exhibit antihypertensive activity in spontaneously hypertensive rats and coronary vasodilator activity with minimal negative inotropic activity in the "Langendorff" guinea pig heart in vitro. They have been shown to exert their activity by inhibition of Ca2+ influx across cell membranes. Optimal activity is found among the N-(arylethyl)-5-methoxy-alpha-methyl-2-(phenylethynyl)ben zeneethanamines and -propanamines. PMID- 3346881 TI - 5-Methyl-2-pyrrolidone analogues of oxotremorine as selective muscarinic agonists. AB - A series of N-(4-amino-2-butynyl)-5-methyl-2-pyrrolidones modified only in the amino group was synthesized. The compounds were agonists, partial agonists, and antagonists on the isolated guinea pig ileum. They had greater affinity and lower intrinsic efficacy at ileal muscarinic receptors than the identically modified N (4-amino-2-butynyl)-2-pyrrolidones and N-(4-amino-2-butynyl)succinimides. Dissociation constants in the three series were correlated, suggesting that the compounds had similar mode of binding to muscarinic receptors. The 5-methyl-2 pyrrolidones were 10- to 20-fold less potent as muscarinic agonists on the guinea pig urinary bladder than on the ileum and also elicited lower relative maximal responses on the bladder. For example, the trimethylammonium (9) and azetidino (10) analogues were equipotent (EC50 = 0.2 microM) with the selective muscarinic stimulant N-(1-methyl-4-pyrrolidino-2-butynyl)-N-methylacetamide, BM 5 (2), as agonists on the ileum, but on the bladder 9 and 10 were relatively weak partial agonists, whereas 2 was an antagonist. Compound 10, like 2 and the dimethylamino analogue 8, also differentiated between centrally mediated muscarinic effects in vivo as it was potent in producing analgesia and hypothermia but did not elicit tremor. Instead, 10 antagonized oxotremorine-induced tremor. Thus, 10 resembled 2 in its actions except that the greater intrinsic efficacy of 10 shifted the balance between agonist and antagonist properties slightly toward agonism. Manipulation of intrinsic efficacy by minor changes in chemical structure is emphasized as a means of attaining selectivity. PMID- 3346883 TI - Potential anticancer agents: 5-(N-substituted-aminocarbonyl)- and 5-(N substituted-aminothiocarbonyl)-5,6,7,8-tetrahydrofolic acids. AB - 5-[[N-[(Ethoxycarbonyl)alkyl]amino]carbonyl] (6-9) and the corresponding aminothiocarbonyl (12-15) derivatives of 5,6,7,8-tetrahydrofolic acid were prepared as multisubstrate analogues of the substrate--cofactor adduct in the reactions catalyzed by the folate-mediated one-carbon transfer reactions. Evaluation in vitro showed that 7 (alkyl = hexyl) was cytotoxic to H.Ep.-2 cells (ED50, 4 microM) but noncytotoxic to proliferating L1210 cells. No activity was observed for 7 against the P388 leukemia in mice. PMID- 3346882 TI - 6- and 8-hydroxy-3,4-dihydro-3-(dipropylamino)-2H-1-benzopyrans. Dopamine agonists with autoreceptor selectivity. AB - The dopamine agonist profiles of 3,4-dihydro-3-(3-dipropylamino)-2H-1-benzopyran 6- and -8-ol (4 and 5, respectively) were examined. Both 4 and 5 exhibited greater relative affinity for receptors labeled with the dopamine agonist ligand [3H]propylnorapomorphine than for those labeled with the dopamine antagonist ligand [3H]haloperidol. Both compounds attenuated the stimulation of brain dopamine synthesis caused by gamma-butyrolactone (GBL) and decreased the firing rate of substantia nigra dopamine neurons in rats. This profile of activity, together with the ability of the dopamine antagonist haloperidol to reverse the inhibition of dopamine neuronal firing, indicate that both compounds are brain dopamine agonists. PMID- 3346884 TI - A recessive form of congenital contractures and torticollis associated with malignant hyperthermia. AB - Two families are presented, each with two affected sibs, all four of whom seem to have a newly described and specific form of congenital contractures (arthrogryposis). The affected subjects have congenital torticollis, dysmorphic, asymmetrical, myopathic facial features, and progressive scoliosis. Two sibs had cleft palate. Malignant hyperthermia has occurred in two of the patients. PMID- 3346885 TI - Absence of a lateral rectus muscle associated with duplication of the chromosome segment 7q32----q34. AB - Absence of the right lateral rectus muscle and hypoplasia of the left was found in a child with congenital esotropia. He had mental and physical retardation, bilateral optic nerve hypoplasia, and many minor dysmorphic features, including brachycephaly, high forehead, poorly folded, low set ears, epicanthic folds, exaggerated Cupid's bow, long philtrum, and single palmar creases. Unusual features were a markedly ridged palate and a plantar crease which passed from the first and second interspace across the lateral border of the foot. He was found to have an unbalanced karyotype with duplication of chromosome segment 7q32--- q34 (46,XY,der(2),inv?ins(2;7) (q21;q32q34)mat). The mother, maternal aunt, and sister of the proband all had a balanced rearrangement and were phenotypically normal. PMID- 3346886 TI - Concurrent de novo interstitial deletion of band 2p22 and reciprocal translocation (3;7)(p21;q22). AB - A child is described with a de novo interstitial deletion of band 2p22 and a reciprocal translocation (3;7)(p21;q22). The child has mild developmental delay, coloboma of the right eye, and Hirschsprung's disease. The clinical and cytogenetic findings are described. PMID- 3346887 TI - Craniofrontonasal dysplasia. PMID- 3346888 TI - Ectrodactyly in sisters and half sisters. PMID- 3346889 TI - Fryns syndrome. PMID- 3346890 TI - The quality of care received by older patients in 15 university-based ambulatory practices. AB - To evaluate how the medical problems of older patients are managed in university based internal medicine practices, the authors reviewed the medical records of 1,527 outpatients treated at 15 university teaching hospitals. Specific treatments for hypertension or diabetes had similar frequencies in patients 65 years of age and over and in patients under age 65. However, although the medical records mentioned hypertension in 43 percent and diabetes in 12 percent of the patients 65 or over, dementia and incontinence were recorded in only 0.4 percent and 2 percent, respectively. This finding suggests either that these elderly patients were extremely atypical or that their geriatric problems were unrecognized. PMID- 3346891 TI - Effects of stress and social phobia on medical students' specialty choices. AB - As a consequence of stress in medical school, the careers of students with social phobia might be significantly influenced by behaviors and decisions based on avoidance of stressful situations. In 1985 third- and fourth-year students at Wright State University School of Medicine were asked to rate specialties as most and least stressful, to indicate whether they considered stress to be favorable or unfavorable, and to complete instruments measuring their stress and social phobia. Contrary to the investigators' expectations, there was no significant association among high stress, social phobia, and choice of least stressful specialties. Certain students who indicated that stress was unfavorable nevertheless chose high-stress specialties. Implications of these findings are discussed, and the findings are compared with outcomes of related studies. PMID- 3346892 TI - A medical school fellowship program for minority high school students. AB - The effectiveness of a research program for minority high school students was evaluated. The program, supported by funding from the National Institutes of Health, was begun in 1982; during the subsequent five years, there were 59 applicants and 38 participants in the program. Of the responding 20 participants, 12 were pursuing careers in science and medicine, and half of the 16 respondents with career plans reported that the program had influenced their career decisions. Overall and in each year, black male students were underrepresented in both the applicant pool and the participants as compared with the metropolitan high school population. PMID- 3346893 TI - A course component to teach interviewing skills in informing and motivating patients. AB - In the present study, the authors implemented and evaluated a course component to teach three types of interviewing skills: giving information to patients, handling emotions on the part of patients, and motivating patients. The authors developed a seven-week course for second-year students that included identification and demonstration of explicit interviewing skills, practice with simulated patients, and feedback in a small-group setting. Thirty of the 104 students in the course were randomly selected for evaluation before and after the course. They showed statistically significant increases in their interviewing skills, based on ratings of videotaped interviews with simulated patients after the course, but did not change significantly in self-assessment of their level of confidence in aspects of conducting the interviews. PMID- 3346894 TI - Institution-wide program for impaired residents at a major teaching hospital. AB - An institution-wide program for residents impaired by alcohol, other drugs, or emotional problems was established in 1983 at the Medical College of Wisconsin Affiliated Hospitals. The goal of the program was to help impaired house staff members to continue their training in a nonpunitive environment. An approach to reviewing allegations of impairment and a legal agreement between the hospital and the recovering resident were implemented. Because no residents were reported for impairment during its first two years, the program's emphasis was shifted from an investigative to an educational, assistive role. Major problems in carrying out the program have been the program's lack of authority to ensure cooperation by program directors and by impaired residents; a widespread unfamiliarity with intervention procedures despite efforts to inform residents, their spouses, faculty members, and administrators about the program; and misconceptions that the program is punitive. Further impediments are lack of a budget to provide educational activities, inadequate socializing between the faculty and the house staff that would enable faculty members to recognize early signs of impairment; and inadequate health insurance coverage for long-term treatment. PMID- 3346895 TI - Attitudes of medical undergraduates and practitioners toward diagnostic accuracy. PMID- 3346897 TI - Use of a simulation to teach central venous access. PMID- 3346896 TI - A pilot study of a medical information system for family physicians in practice. PMID- 3346898 TI - Alcoholism education. PMID- 3346899 TI - Duke curriculum. PMID- 3346900 TI - Lack of correlation between haemagglutination and adherence to epithelial cells in Yersinia pseudotuberculosis. AB - Yersinia pseudotuberculosis was examined for its haemagglutinating activity and adherence to cultured epithelial cells (HEp-2) in relation to possession of a virulence (VW) plasmid and to growth conditions. VW-lacking (VW-) bacteria were isolated from ten VW+ strains of each serovar which, after they were grown on CFA plates at 37 degrees C, agglutinated the erythrocytes from five different species. In contrast to the bacteria possessing the plasmid (VW+) half of the VW- bacteria, grown on CFA plates at 37 degrees C, did not agglutinate any of the erythrocytes used and the other half agglutinated only human erythrocytes. Furthermore, when grown on CFA plates at 25 degrees C, neither VW+ nor VW- bacteria showed a haemagglutinating activity. When the bacteria were grown in CFA broth, only two strains grown at 25 degrees C did not agglutinate any of the erythrocytes tested. The VW+ and VW- bacteria of the remaining strains, grown either at 25 degrees C or 37 degrees C, showed relatively high haemagglutinating activity. Adherence to HEp-2 cells did not correlate with haemagglutinating activity in Y. pseudotuberculosis; the VW+ bacteria grown at 37 degrees C adhered to HEp-2 cells more efficiently than either the VW- derivatives or the VW+ bacteria grown at 25 degrees C, regardless of the growth medium. These results indicate that some of the haemagglutinins detected on Y. pseudotuberculosis are not involved in the adherence to HEp-2 cells. PMID- 3346901 TI - Production of monoclonal antibody against Aeromonas hydrophila haemolysin. AB - Two hybridoma cell lines that produce monoclonal antibodies against Aeromonas hydrophila haemolysin were established by fusion of myeloma and spleen cells obtained from a mouse immunised with haemolysin detoxified with tetranitromethane. Enzyme-linked immunosorbent assay (ELISA) showed that the two purified monoclonal antibodies, B7 and B11, recognised the same epitope on the haemolysin molecule. Antibody B7 neutralised the haemolytic and enterotoxic activities of the haemolysin. It is concluded that the same site on the haemolysin molecule is responsible for both haemolytic and enterotoxic activities. PMID- 3346902 TI - Mucosal association by Clostridium difficile in the hamster gastrointestinal tract. AB - For many organisms, mucosal association is an important virulence determinant. Although studied in detail for other intestinal pathogens, this aspect of pathogenicity has not been studied for Clostridium difficile. We compared the ability of an avirulent non-toxigenic strain (M-1), a highly virulent toxigenic strain (B-1), and a poorly virulent toxigenic strain (BAT) of C. difficile to adhere to different regions of the gastrointestinal tract of hamsters pre-treated with clindamycin. Strain B-1 associated with the gut mucosa significantly better than strain M-1 (p less than 0.001) for all sites other than the caecum, and achieved significantly higher levels in the caecal contents (p less than 0.001). The same was true when strain B-1 was compared with strain BAT except that there was no significant difference for the large bowel mucosa. To assess the possible role of toxin in promoting mucosal association, e.g., by compromising host defences or exposing masked adherence sites, strain M-1 was given to animals after intra-caecal administration of crude toxin preparations from strain-B1, which were heat-inactivated in control experiments. The addition of this toxin increased significantly the mucosal association of M-1 for the small bowel only, whereas the inactivated toxin had no significant effect. These results imply that there may be intrinsic differences between strains in their ability to colonise and associate with the gut mucosa, which may partly depend on their ability to produce toxin. These differences do not correlate with cell-surface hydrophobicity or the presence of plasmids, flagella or fimbriae. PMID- 3346904 TI - The 1987 James Grant Thompson lecture: What everybody should know about vascular trauma. PMID- 3346905 TI - The miniature battery: a new foreign body hazard. PMID- 3346906 TI - Radiological seminar CCXLIX: the role of radiographic evaluation in the diagnosis of epiglottitis. PMID- 3346903 TI - The inhibitory effect of serum on the growth of Torulopsis glabrata. AB - Normal human plasma and serum were found to inhibit the growth of Torulopsis glabrata and, to a lesser extent, other yeasts. The factor responsible for the inhibition of T. glabrata was not dialysable, was heat stable at 56 degrees C for up to 4 h and could be partly removed by absorption with viable T. glabrata but not Candida albicans. It was fungistatic at low concentrations and fungicidal at high concentrations, stable up to 4 years between -20 degrees C and -70 degrees C, but for only a few weeks at 4 degrees C. Studies with Cohn fractions of serum showed that the inhibitory components were in either the alpha or beta globulin fraction or both. The combined effects of transferrin and IgM accounted for about 70% of the total inhibition observed. We were unable to identify the component responsible for the residual inhibition of growth. The inhibitory effect was totally neutralised by tetracyclines, quinolones, sulphamethoxazole and by very low concentrations of polyenes, imidazoles and 5-fluorocytosine. PMID- 3346907 TI - Current concepts: care and habilitation of the child with myelomeningocele. Part VII. Myelomeningocele: adolescence/ sexuality/vocational skills. PMID- 3346908 TI - Mathematical modeling for tumor resistance. PMID- 3346909 TI - Interferon-induced changes in pharmacokinetics and tumor uptake of 111In-labeled antimelanoma antibody 96.5 in melanoma patients. AB - The type I interferons [both partially purified human leukocyte interferon (HuIFN alpha) and recombinant alpha interferon] and the type II interferons have been shown to increase the expression of tumor-associated antigens in vitro. To determine whether HuIFN-alpha could increase tumor acquisition of the antimelanoma antibody 96.5 in vivo, five patients with metastatic malignant melanoma were treated with HuIFN-alpha at a dose of 3 X 10(6) units daily by im administration. Twenty-four hours after the first dose of HuIFN-alpha, 1 mg of antibody 96.5 labeled with 5 mCi of 111In was coadministered with 19 mg of unlabeled 96.5. Five patients matched for metastatic site and lesion size who had not received HuIFN-alpha were also given a dose of 5 mCi of radiolabeled 96.5 at the same total antibody dose (20 mg). In patients treated with HuIFN-alpha, there was a statistically significant increase in the plasma half-life of the 111In label (39.7 +/- 3.3 hr) compared to the untreated control group (29.8 +/- 3.2 hr). In addition, there was an increase in the apparent volume of distribution of the antibody in the HuIFN-alpha group (5.56 +/- 0.67 L) compared to controls (3.15 +/- 0.5 L) suggesting both an increased immediate extravascular distribution of radiolabeled antibody and a decrease in the subsequent rate of clearance of antibody from plasma. These two phenomena result in a 28% decrease in the area under the concentration curve in the HuIFN-alpha-treated group compared to controls. Computer analysis of whole-body scans from patients showed a threefold increase in radiolabeled antibody distributed to tumor relative to blood pool but no change in organ:blood ratios for liver, spleen, bone, or kidney compared to controls. This pilot study suggests that treatment of patients with HuIFN-alpha results in an improved distribution of radiolabeled antibody to tumor target without a concomitant increase of label in normal nontarget tissues. In addition, this change in whole-body distribution of antibody is manifested by changes in the pharmacokinetic parameters measured for monoclonal antibody. PMID- 3346910 TI - Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation. AB - The contribution of lipid peroxidation to the killing of human breast cancer cells by gamma-linolenate (GLA) was examined. Other fatty acids of different cytotoxic potential containing 2, 4, 5, and 6 double bonds were also tested for comparison. It was found that the cytotoxic potential varied with the ability of the fatty acids to stimulate the production of superoxide radicals. Neither hydrogen peroxide nor hydroxy radicals are significantly involved in cell killing. As nonspecific indicators of lipid peroxidation, measurements of the loss of unsaturated fatty acid in the phospholipids together with the generation of hydroperoxide breakdown products were done with the use of the thiobarbituric acid test. The results of these experiments showed that the effectiveness of a given fatty acid in killing cancer cells correlated with the intracellular thiobarbituric acid-reactive material (TBARM) content: GLA and arachidonate with 3 and 4 double bonds generated the most TBARM and were the most cytotoxic fatty acids, whereas docosahexaenoate with 6 double bonds was the least effective either in raising TBARM or in killing the malignant cells. Iron and copper accelerated the rate of cell death, whereas antioxidants such as vitamin E and butylated hydroxyanisole inhibited the effect of GLA dose dependently. Indomethacin, an inhibitor of endoperoxide formation, did not reduce either cell kill or TBARM amounts. In contrast, the addition of vitamin E acetate to the cancer cell cultures challenged with eicosapentaenoate reduced both cell killing and TBARM content. These results suggest that the effectiveness of a given fatty acid in killing cancer cells correlated with the extent of lipid peroxidation of the added fatty acid in the cells. PMID- 3346911 TI - Derivatives of amsacrine: determinants required for high activity against Lewis lung carcinoma. AB - Antitumor activity against the Lewis lung carcinoma in mice is reported for the series of 36 acridine-substituted derivatives of the antileukemia agent amsacrine. This series is the one from which the analogue N,5-dimethyl-9-[(2 methoxysulfonylamino)phenylamino]-4-acridinecarboxamide (CI-921), presently in clinical trial, was chosen. The analogues also were tested in vitro by comparing growth inhibition data [IC50 values (concentration required to reduce growth of cultured cells to 50% of that of untreated cultures)], using L1210 murine leukemia cells and HCT-8 human colon carcinoma cells. Determined IC50 values were highly dependent on the culture medium used, and it was found that the presence of ascorbate in the medium had a major effect on the stability of compounds to oxidation. A survey of 115 analogues of amsacrine indicates that a low ratio of IC50 values (HCT-8/L1210) is necessary but not sufficient for good antitumor activity against the solid tumor. DNA binding constants did not in themselves predict activity, although they were related to dose potency. Other factors, such as drug lipophilicity, acridine base strength, and drug solubility, also are involved, probably in providing effective drug distribution. It is concluded that in vitro assay data provide information useful for drug design but that other factors also are important for in vivo activity. PMID- 3346912 TI - Evidence for a novel gene associated with low tumor metastatic potential. AB - We describe a gene, NM23, that is associated with the tumor metastatic process. NM23 RNA levels were highest in cells and tumors of relatively low metastatic potential in two experimental systems: (1) murine K-1735 melanoma cell lines, in which the gene was identified, and (2) N-nitroso-N-methylurea-induced rat mammary carcinomas. NM23 RNA levels did not correlate with cell sensitivity to host immunological responses and may, therefore, be associated with intrinsic aggressiveness. The predicted carboxy-terminal protein sequence encoded by the pNM23 cDNA clone is novel compared with Genebank animal, bacterial, and viral sequences. PMID- 3346913 TI - Tissue expansion for the reconstruction of burn defects. AB - Tissue expansion has emerged recently as an alternative reconstructive procedure and has been used for the treatment of a variety of defects. This paper presents our experience with the use of tissue expansion exclusively for the treatment of secondary burn defects. The technique was used in 22 consecutive patients. The technical aspects of the procedure are described. The advantages of tissue expansion, including the superior quality of reconstruction, cost effectiveness, and absence of donor site scar are presented. The disadvantages, including the need for two stages, multiple office visits, its application for relatively small defects, and the objectionable temporary appearance, are discussed. Finally, patient selection, and refinements of the technique and tailoring of the expanded flaps to achieve the best possible reconstructive and esthetic results and limit the possibility of complications are discussed. PMID- 3346914 TI - Cardiopulmonary responses after spontaneous inhalation of Douglas fir smoke in goats. AB - In the majority of clinical cases, smoke inhalation results in a self-limited lung injury mostly confined to the airways. In this study, an animal model of inhalation injury was developed that reflected similar pathophysiology. Cardiopulmonary parameters were studied in awake, instrumented goats following spontaneous inhalation of characterized Douglas fir smoke. Peak carboxyhemoglobin levels averaged 37% during a mean exposure time of 33 minutes. All animals survived the 24-hour study period, and showed only transient abnormalities in lung fluid balance and gas exchange, with no change in lung mechanics or plasma eicosanoid (TxB2 and 6-keto-PGF1 alpha) levels. However, extravascular lung water at 24 hours was increased 33%, suggesting the presence of some airway edema and retained secretions. We feel this model fairly represents the majority of clinical smoke inhalation cases. This model is compared to other large animal inhalation injury models producing more severe lung injury. PMID- 3346916 TI - Effect of exchange transfusion on cell-mediated immune function following thermal injury. AB - We assessed the effect of syngeneic and allogeneic exchange transfusion (XTF) on cell-mediated immunity in a murine burn model. Mice were given a 30% TBSA scald injury and lymphocyte function was monitored with the popliteal lymph node assay for host-versus-graft (HVG) or graft-versus-host (GVH) response. Nonexchanged burned animals exhibited suppression of GVH response on postburn days (PBD) 3 and 8 and suppression of HVG response on PBD 3, 8, 11, and 14. Syngeneic XTF stimulated GVH response on PBD 3, and significantly improved both GVH and HVG response to alloantigens on postburn days 3 and 8 compared to the response of burned controls. Allogeneic XTF significantly improved GVH response on PBD 3 and 8, but did not improve HVG response. Restoration of lymphocyte function in all experimental groups occurred between PBD 14 and 18 and coincided with wound healing. PMID- 3346915 TI - Cyanide toxicity in burned patients. AB - The role of cyanide (CN) in smoke inhalation injury has been the subject of investigation for many years. Prospective evaluation of serum CN, thiocyanate (the primary metabolic product of CN), and carboxyhemoglobin (COHb) in patients suspected by history of having smoke inhalation injury was performed in 144 patients. Eight of 12 patients with "lethal" CN levels (greater than 1.0 mg/L) died. All had sublethal levels of COHb. A separate group of patients who were DOA following fatal burn injuries were also studied. Lethal CN levels were found in 12 of 14 victims with lethal COHb levels and in 14 of 20 victims with sublethal COHb levels. The results show that elevated CN levels are frequent in patients with smoke inhalation and suggest that cyanide toxicity is a contributor to severe inhalation injuries. In some cases, CN was the primary measured toxicant. PMID- 3346918 TI - Wound coverage with cultured autologous keratinocytes: use after burn wound excision, including biopsy followup. AB - Cultured autologous keratinocytes (CAK) have been used in eight patients as part of their definitive treatment for burn wound closure. The CAK grafts were placed on surgically excised wounds rather than mature granulation tissue. This technique guaranteed that permanent skin coverage derived from cultured cells, and not residual epidermal cells from surviving dermis. Graft take was variable, ranging from zero in the case of one of the children to 85%. Long-term assessment noted adequate permanent coverage, confirmed by biopsy. Electron micrographs demonstrated no well formed anchoring fibrils, which may account for the graft fragility which has been reported as much as 1 year postgraft. Advantages of using CAK are that an acceptable permanent wound closure can be achieved without depending on donor site availability. An almost unlimited quantity of skin is available because the original biopsy can be expanded manyfold in the laboratory. PMID- 3346917 TI - Effect of anti-PGE antibody on cell-mediated immune response in thermally injured mice. AB - Prostaglandin E (PGE) production is elevated in burn-injured individuals and has been implicated as a mechanism in thermal injury-induced immunosuppression. Profound depression of cell-mediated immune response (CMIR) is a characteristic effect of burn injury, and was evaluated using the popliteal lymph node assay for graft-versus-host and host-versus-graft responsiveness in mice. Preservation of CMIR after burn injury was observed in animals treated with 40 mg/kg ibuprofen and in mice given anti-PGE antibody. It appears that PGE is a central immunoregulatory mediator of suppressed CMIR following thermal injury and that treatment resulting in inhibition of PGE production or neutralization of PGE with anti-PGE antibody prevented burn-induced immunosuppression. PMID- 3346919 TI - Elastase and suppressor active peptide activity following burn injury. AB - Proteolytic enzyme activity following trauma and inflammation plays a key role in the pathophysiology of injury. The precise mechanisms involved in the induction of protease release has not been determined. We show here that sera from burn patients with greater than 40% TBSA have significantly elevated levels of active elastase which correspond with significantly increased levels of suppressor active peptide (SAP) and suppression of neutrophil chemotaxis. The elastase inhibitory capacity of serum from burned or blunt trauma patients was within normal range, suggesting that the primary elastase inhibitor, alpha-1-proteinase inhibitor, is functionally active. Additionally, granulocytes exposed to suppressor active peptide in vitro resulted in a markedly elevated release of elastase into the culture supernatants. These data suggest that the suppressor peptide is capable of not only suppressing immune function but is also a potent mediator for the induction of proteolytic enzyme release from leukocytes. PMID- 3346920 TI - Reconstruction of axillary burn contractures with the latissimus dorsi fasciocutaneous flap. AB - Standard management of axillary burn contractures has been scar release and the use of skin grafts, despite the common problem of incomplete graft take, prolonged splinting, extended physical therapy, and recurrent contractures. A recent development in plastic surgery has been the "super flap" or fasciocutaneous flap. A series of axillary burn contractures released with the latissimus dorsi fasciocutaneous flap has been reported by Tolhurst. Our series of ten patients confirms that the latissimus dorsi fasciocutaneous flap is the treatment of choice for the release of severe axillary burn contractures. PMID- 3346922 TI - Child abuse by burning--an index of suspicion. AB - Although general awareness of child abuse is increasing, abuse by burning is often unrecognized. Seventy-one consecutive children admitted with inflicted burns were studied. Mean age was 1.8 yrs and mean burn size was 13.5%. Mean length of stay was 18.9 days. Scalds (83% from tap water) were the most frequent cause of injury. An immersion pattern was present in 59%; six patients had a classic forced immersion injury. Fourteen children had nonburn trauma. Four patients died: all had tap water immersion burns. Inflicted burns are usually manifested by characteristic patterns of injury, which must be correlated with the given history. When compared with accidentally burned children, abused children were significantly younger, had longer hospital stays, and had a higher mortality. A team approach to child abuse with the addition of a specially trained group is important to insure prompt recognition, more objective appraisals, and further followup. PMID- 3346921 TI - Pulmonary emboli in burned patients. AB - The incidence of and prophylaxis against clinically important pulmonary emboli (PE) in burned patients is an often discussed problem. To study its magnitude, all patients admitted with acute burns were followed for clinical evidence of thromboembolism: 2,106 patients were evaluated (1,439 adults). No children had evidence of PE. Six adults (0.4%) sustained a PE: none died. Mean burn size was 26.8%; mean age, 35.1 years; and mean weight, 90.8 kg. Mean PBD of the PE was 16.5 days. None with PE were ICU patients and none had lower-extremity IV lines. Two patients had embolic events after discharge from the hospital. No ICU patients who died unexpectedly had a PE. Only two patients had significant risk factors; they were obese with leg burns. Three had no risk factors; normal weight and upper body burns without prolonged bed rest. The incidence of pulmonary emboli and resulting morbidity do not justify routine prophylactic heparinization of all burned patients. PMID- 3346923 TI - Optimal management of tibial arterial trauma. AB - In an attempt to define optimal management, we have studied the outcome of 29 isolated tibial arterial injuries during the past 4 years. Twenty-five patients suffered blunt and four had penetrating trauma. Twenty-seven patients had preoperative arteriography which showed at least one interrupted tibial artery. In nine patients, immediate and successful reconstruction was done. Since the foot was viable in 20 patients, immediate reconstruction was not carried out in spite of the diagnosis of tibial arterial injury. Three of 20 underwent primary amputation. Fifteen of the remaining 17 patients required further angiographic evaluation for arterial reconstructions 2 to 12 months later for nonhealing of wounds, malunion of fractures, and soft-tissue defects. Delayed reconstructions were generally more complex. In 13 patients both viable and functional feet were eventually achieved. Bypass with autogenous vein was mandatory for success. Our experience has shown that most tibial arterial trauma will require immediate repair for success. Delayed repair was more difficult and was associated with substantial limb loss. PMID- 3346924 TI - The effect of medical direction on trauma triage. AB - Effective field triage of trauma victims requires identification of patients at risk of dying and their rapid transport to hospitals capable of treating severe injuries. Identification of these patients at the accident scene can be difficult since prehospital personnel receive little training in structured triage decision making. The role of the physician in routine triage is disputed and his/her value has not been documented. This study explored the severity of injury of three groups of trauma patients triaged by different guidelines to a Level I urban trauma center. Results showed that with physician input in the triage process, patients chosen for helicopter transport to the trauma center had a significantly higher median level of injury severity than patients triaged to the trauma center without physician involvement. The results have implications for controlling overtriage of patients to trauma centers. PMID- 3346925 TI - Trauma angiography: the use of clinical findings to improve patient selection and case preparation. AB - Two-hundred eighty angiographic studies performed for suspected acute arterial trauma were reviewed to evaluate the relationship between the clinical findings and arterial injury. Extremity injury occurred in 237 cases. The proximity of a penetrating injury or a fracture to a major vascular structure was the sole indication for angiographic study in 136. No major arterial injury was discovered in either group. Exclusion of these patients would have improved the extremity angiographic yield from 25% to 58% while missing no patients with major arterial injury. We conclude, based on the negligible yield, that clinical observation of these patients is a safe alternative if adequate followup is assured; elective angiography may be performed if followup is questionable. Nineteen of 20 (95%) patients with an absent distal pulse and clinical signs of extremity ischemia had a major arterial injury. All extremity arterial injuries occurred within 5 cm of bullet fragments, bone fragments, entrance wound, or exit wound. Given the virtual assurance of finding major arterial injury, patients with unifocal injury and a threatened limb may proceed directly to the operating room to minimize ischemic time. PMID- 3346926 TI - A nonbacterial cause of post-traumatic soft-tissue gas. AB - A young male sustained a wound on the lateral aspect of the right thigh, presenting 24 hours later with subcutaneous crepitus over the thigh. He was systemically well, Gram stains and wound culture were negative. The cause was a sucking wound due to the valvelike action of the iliotibial band. PMID- 3346927 TI - Intra-articular dislocation of the patella. AB - A very rare case of intra-articular dislocation of the patella in a 10-year-old boy is presented. Closed reduction was successful. After reduction, X-rays showed normal patello-femoral alignment. PMID- 3346928 TI - An unusual cause of mitral incompetence: post-traumatic paraprosthetic mitral incompetence. AB - Nonpenetrating chest trauma, particularly that involving high-speed, may cause a variety of cardiac and aortic injuries. Cardiac valvular disruption following trauma is uncommon. Two cases of paraprosthetic mitral incompetence following blunt chest trauma are presented to document this entity and to discuss its investigation and management. Clinical examination and a high index of suspicion are foremost in making the diagnosis. Noninvasive tests may not confirm clinical diagnosis and cardiac catheterization has provided confirmation of clinical diagnosis. PMID- 3346929 TI - Transient heart block associated with head trauma. AB - Atrioventricular nodal block is a rare consequence of head trauma. We report a case of a 63-year-old male with coronary artery disease who sustained a skull fracture. Twelve hours later the cardiac monitor recorded an episode of high grade atrioventricular block with a ventricular escape rhythm. Subsequent electrophysiologic evaluation revealed no abnormality of atrioventricular nodal conduction nor of intraventricular conduction. Atrioventricular block after head trauma may be caused by enhanced vagal tone. PMID- 3346931 TI - Diabetes mellitus in Benghazi. AB - The records of 10,772 diabetic patients registered in Benghazi diabetic clinic during the period 1969-1985 were analysed. Non-insulin dependent diabetes mellitus (NIDDM or type II) accounted for 97.8% of patients. Of the whole clinic population 77.2% were below 40 years of age. The disease started below the age of 20 years in 1.9%. Male to female sex ratio was 1:1.2. Family history of diabetes was positive in 23.77%. Sixty-nine per cent of patients were obese. Patients presented with symptoms suggestive of diabetes mellitus in 79.7% of cases. PMID- 3346930 TI - Bacteriological contamination of water in rural areas: an intervention study from Malawi. AB - The bacteriological quality of drinking water sources and of stored household water was examined in a rural area of Malawi, before and after improvement of the method of water supply. Among the traditional water sources, water quality was better in springs than in wells and rivers. During the rainy season, there was a considerable deterioration of water quality, which was most pronounced in wells. The improved water supply system consisted of piped, untreated surface water from an uninhabited mountain area. This water contained a mean value of 54 faecal coliforms per 100 ml which can be regarded as acceptable in this setting. During collection of drinking water and during household storage, there was considerable contamination, which mirrored the unhygienic environment. Contamination was worse during the rainy season than during the dry season. Technical interventions aimed at improving water supply in rural areas of developing countries will probably not become effective unless combined with comprehensive health education programmes for the population concerned. PMID- 3346932 TI - Evaluation of home-made salt-sugar oral rehydration solution in a rural Nigerian population. AB - Standardized local measures for preparing oral rehydration solution (ORS) in Nigeria were re-evaluated under laboratory conditions. Our results confirm those of the standardization team in respect of granulated and cube sugar. However, our mean weight of one salt measure (2.8155 +/- 0.292 g) is about 20% greater than their value. Consequently, correct use of the measures in our study gave solutions of 211-297 mmol-1 total concentration and 60-80 mmol-1, Na+ as against their values of 173-251 mmol 1-1 and 45-70 mmol-1, respectively. This discrepancy is most likely due to differences in salt type. Analysis of home-made solutions prepared by 40 illiterate mothers showed that 60% of them made accurately composed solutions. All the rest made hypertonic solutions. Salt type, spoon size and levelling technique are all possible causes of their error. The tendency to err only on the side of greater rather than lower salt concentration may be culture based or simply due to natural maternal instinct. To combat this trend, health education programmes in Nigeria should emphasize the danger in feeding a hypernatremic solution to a dehydrated child. PMID- 3346933 TI - Factors influencing vaccination compliance in peri-urban Gambian children. AB - The vaccination status of 251 children aged 12-18 months in two peri-urban Gambian communities was determined from their health cards. Two subgroups were identified: children who were fully vaccinated, and those who had received less than half their vaccinations. The social and environmental circumstances of these children were investigated to detect factors which were associated with poor vaccination compliance. Mothers of well vaccinated children were more inclined to bring them for non-curative services. Mothers of poorly vaccinated children had a poorer knowledge of the diseases against which their children should be vaccinated and they also had a more superstitious view of disease causation. Those children who showed poor compliance came from larger families. In the poorly vaccinated group both parents were less well educated and there was a trend towards poorer literacy. PMID- 3346934 TI - Estimating vaccination coverage: routine information or sample survey? AB - The manager of a district immunization programme needs to regularly assess vaccination coverage. This case study from Zimbabwe describes how routine information can be used for this purpose. The number of children and their location in the district was estimated from several sources using a variety of methods. This suggested that under-enumeration at the 1982 census was probably as high as a third and was a particular problem among children aged under 1 year. Routinely collected figures of the number of vaccinations were then used to calculate coverage levels for different health unit catchment areas within the district. These levels varied considerably and were lowest in areas with significant numbers of Apostolics, a group who often reject immunization on religious grounds. Comparisons between estimates of coverage obtained from routine information and a sample cluster survey raised several issues. These included accuracy of routine information, precision of sample surveys, estimating differential coverage in the district, management uses of estimates and the cost of data collection. PMID- 3346935 TI - Foot length measurement from foot print for identifying a newborn at risk. PMID- 3346936 TI - Acute diarrhoea: who needs potassium? PMID- 3346937 TI - Efficacy of oral rehydration solution in correcting serum potassium deficit of children with acute diarrhoea in Bangladesh. PMID- 3346938 TI - Breast feeding and weaning practices in relation to nutritional status of under-5 children in north Bangladesh. PMID- 3346939 TI - Perinatal mortality and neonatal survival in Libya. PMID- 3346940 TI - Predicting risk of delivering low birthweight babies: which indicator is better? PMID- 3346941 TI - Learning from doing: progression to primary health care within a national health programme. A case study from Tanzania. PMID- 3346942 TI - Anthropometric study of Dominican pre-school children. PMID- 3346943 TI - Regulation of interferon gene expression: mechanism of action of the If-1 locus. AB - We have examined the mechanism of action of the If-1 interferon (IFN) regulatory locus. This locus controls the level of circulating IFN produced in inbred mice in response to intravenous injection of Newcastle disease virus. Mice carrying the If-1h (high) allele show circulating IFN levels 10- to 15-fold higher than those carrying the If-1l (low) allele. In this report we show that induced splenocytes from If-1h and If-1l mice produce IFN at levels which are in the same proportions as those found in the circulation. Higher levels of IFN-specific mRNA were observed in splenocyte populations from If-1h animals. This was due to increased transcription of IFN genes. At the same time, the high- and low producing populations showed no significant difference in the number of IFN mRNA containing cells. We conclude that the effect of If-1 in the spleen is to control the levels of transcription of the IFN genes in individual induced splenocytes. PMID- 3346944 TI - Nucleotide sequence of the large double-stranded RNA segment of bacteriophage phi 6: genes specifying the viral replicase and transcriptase. AB - The genome of the lipid-containing bacteriophage phi 6 contains three segments of double-stranded RNA. We determined the nucleotide sequence of cDNA derived from the largest RNA segment (L). This segment specifies the procapsid proteins necessary for transcription and replication of the phi 6 genome. The coding sequences of the four proteins on this segment were identified on the basis of size and the correlation of predicted N-terminal amino acid sequences with those found through analysis of isolated proteins. This report completes the sequence analysis of phi 6. This constitutes the first complete sequence of a double stranded RNA genome virus. PMID- 3346945 TI - Transformed and tumorigenic phenotypes induced by avian retroviruses containing the v-mil oncogene. AB - Avian retrovirus MH2 contains two oncogenes, v-mil and v-myc. We have previously shown that a spontaneous mutant of MH2 (PA200-MH2), expressing only the v-mil oncogene, is able to induce proliferation of quiescent neuroretina cells. In this study, we investigated the transforming and tumorigenic properties of v-mil. PA200 induced fibrosarcomas in about 60% of the injected chickens, whereas inoculation of MH2 resulted mainly in the appearance of kidney carcinomas. Analysis of several parameters of transformation showed that PA200, in contrast to MH2, induced only limited in vitro transformation of fibroblasts and neuroretina cells. These results suggest that v-myc is the major transforming and tumorigenic gene in MH2-infected cells. This low in vitro transforming capacity differentiates v-mil not only from other avian oncogenes, but also from the homologous murine v-raf gene. PMID- 3346946 TI - Molecular analysis of viral RNAs in mice persistently infected with lymphocytic choriomeningitis virus. AB - Infection of newborn mice with lymphocytic choriomeningitis virus (LCMV) results in a lifelong persistent infection. Persistently infected animals continuously produce low levels of infectious virus and accumulate large amounts of intracellular viral nucleic acid (P. J. Southern, P. Blount, and M. B. A. Oldstone, Nature [London] 312:555-558, 1984). We have used gel electrophoresis and hybridization techniques to analyze viral RNAs that appear during the establishment and maintenance of a persistent LCMV infection in vivo to identify any role for defective and/or defective interfering RNAs. We have found a complex, heterogeneously sized population of viral RNAs in multiple independent tissues that is uniquely associated with persistent infections in vivo, but we have not yet established whether these RNAs have a causal or a consequential association with persistent infection by LCMV. Within the complex virus RNA population, full-length genomic L and S RNAs were readily detectable and represented the most abundant individual viral RNA species. RNAs apparently corresponding in size to the viral nucleoprotein and glycoprotein mRNAs could also be detected in these tissue RNA samples. The presence of glycoprotein mRNA indicates a potential mechanism of posttranscriptional regulation to account for the previously documented restriction in viral glycoprotein expression in persistently infected mice (M. B. A. Oldstone and M. J. Buchmeier, Nature (London) 300:360-362, 1982). PMID- 3346947 TI - Drosophila S virus, a hereditary reolike virus, probable agent of the morphological S character in Drosophila simulans. AB - Isometric reolike virions were found in all the examined Drosophila simulans flies from two strains (SimES-st and Israel-st) presenting the S phenotype, a maternally inherited morphological trait (abnormalities of bristles). Normal flies of both strains appeared virus-free. Virions were found in the cytoplasm of male and female gonads and epidermal cells, including the bristle-forming cells, which appeared disorganized. Steps of virogenesis were described. A positive correlation was demonstrated between expressivity of the S phenotype and degree of viral infection. This hereditary reolike virus seems to be responsible for the S character of D. simulans and was named DSV (Drosophila S virus). PMID- 3346949 TI - A chronic carrierlike state is established in nude mice injected with cloned hepatitis B virus DNA. AB - BALB/c nude mice were injected intrahepatically with hepatitis B virus (HBV) DNA prepared from recombinant plasmids. Hepatitis B surface antigen appeared in the circulation in 19 of 23 mice (82%) 3 to 20 weeks postinjection and persisted for more than 6 months in most animals. Hepatitis B e antigen appeared transiently in the circulation in 12 of the 23 mice (52%) within a few weeks after the appearance of hepatitis B surface antigen. Antibodies to the core, X, and/or polymerase gene products of HBV have also been observed in 14 (61%) of the mice. Histopathological examination of the livers at 7 months postinjection demonstrated that nearly half had characteristics consistent with chronic hepatitis. HBV DNA appeared to be integrated into host liver DNA. No evidence of viral replication was observed in sera or livers from these mice at 7 months postinjection. These results demonstrate that an HBV chronic carrierlike state can be established in mice and that such a model could be used to study host and virus factors important in the establishment and maintenance of HBV-associated chronic liver disease. PMID- 3346948 TI - Multiple viral mutations rather than host factors cause defective measles virus gene expression in a subacute sclerosing panencephalitis cell line. AB - A measles virus (MV) genome originally derived from brain cells of a subacute sclerosing panencephalitis patient expressed in IP-3-Ca cells an unstable MV matrix protein and was unable to produce virus particles. Transfection of this MV genome into other cell lines did not relieve these defects, showing that they are ultimately encoded by viral mutations. However, these defects were partially relieved in a weakly infectious virus which emerged from IP-3-Ca cells and which produced a matrix protein of intermediate stability. The sequences of several cDNAs related to the unstable and intermediately stable matrix proteins showed many differences in comparison with a stable matrix protein sequence and even appreciable heterogeneity among themselves. Nevertheless, partial restoration of matrix protein stability could be ascribed to a single additional amino acid change. From an examination of additional genes, we estimated that, on average, each MV genome in IP-3-Ca cells differs from the others in 30 to 40 of its 16,000 bases. The role of extreme variability of RNA virus genomes in persistent viral infections is discussed in the context of the pathogenesis of subacute sclerosing panencephalitis and of other human diseases of suspected viral etiology. PMID- 3346950 TI - The two transcription units of the autonomous parvovirus minute virus of mice are transcribed in a temporal order. AB - Using quantitative RNase protection assays, we have monitored the appearance of mRNAs generated during lytic infection of tightly synchronized murine cells by the autonomous parvovirus minute virus of mice. Our results demonstrate that transcripts from the P4 promoter can be detected prior to those from the P39 promoter, providing direct evidence for a temporal order of expression between the two parvovirus promoters. PMID- 3346951 TI - Evaluation of a proposed standard reporting system for preoperative angiograms in infrainguinal bypass procedures: angiographic correlates of measured runoff resistance. AB - Preoperative angiography is widely used to estimate runoff before peripheral vascular bypass surgery. The Ad Hoc Committee on Reporting Standards for the Society for Vascular Surgery and the International Society for Cardiovascular Surgery recently proposed an angiographic scoring system that grades the quality of vessels distal to the proposed bypass site and calculates an overall runoff score after adjusting each vessel score by an arbitrary weighting factor. We compared this score with intraoperatively measured runoff resistance in 67 patients undergoing infrainguinal bypass. Correlation between overall runoff score and measured resistance varied with the distal bypass site and was reasonably predictive for femoropopliteal above-knee bypasses (r = 0.67, p = 0.004, N = 17) and femoroposterior tibial bypasses (r = 0.73, p = 0.03, N = 9), but not for femoropopliteal below-knee (r = 0.05, p = 0.76, N = 34) or femoroperoneal (r = 0.57, p = 0.18, N = 7) bypasses. When multiple linear regression was used to calculate the weighting factors (rather than using arbitrarily assigned factors), the correlation between overall angiogram score and measured resistance improved substantially for femoropopliteal above-knee (r = 0.85, p = 0.00006), femoropopliteal below-knee (r = 0.50, p = 0.03) and femoroperoneal (r = 0.83, p = 0.02) bypasses. Correlation for the entire group of 67 patients improved from r = 0.30 (p = 0.02) to r = 0.64 (p = 0.0001). We conclude that the committee's scoring system correlates with measured runoff resistance but can be improved by the use of multiple linear regression to calculate weighting factors for each vessel in the outflow tract. PMID- 3346952 TI - Differential enlargement of artery segments in response to enlarging atherosclerotic plaques. AB - We studied the relationships among intimal plaque area, lumen area, and artery size in 481 sections of the left anterior descending (LAD) coronary artery taken at four standard sampling sites in 125 pressure-perfusion-fixed postmortem adult human hearts. The internal elastic lamina area was considered to be a measure of artery size or potential lumen area. Artery size correlated strongly with intimal plaque area at each LAD level (p less than 0.0001). Stepwise regression analysis revealed that plaque area was the principal determinant of artery size at each LAD level (r2 = 0.20 to 0.33). Sections of arteries with the most intimal plaque (highest quartile) were compared with those with the least plaque (lowest quartile) at each sample site. In the proximal LAD artery, the most severely diseased arteries increased in size 62% but lumen area decreased 25%. In the midportion of the LAD artery, plaque area was 10 times greater in the most diseased arteries, but lumen area remained normal because of an 80% increase in artery size. In the most severely diseased distal LAD artery sections, despite a fourteenfold increase in plaque area, lumen area almost doubled because of a marked increase in artery size. If no enlargement had occurred, the most severely diseased arteries in the proximal LAD segment would have developed a 92% lumen stenosis rather than the observed 25% lumen stenosis. In the distal LAD artery, without enlargement there would have been a 65% lumen stenosis rather than the 85% increase in lumen area that was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3346953 TI - The use of scintiangiography with technetium 99m in the diagnosis of traumatic pseudoaneurysm. AB - Pseudoaneurysm formation is a known complication of peripheral arterial access procedures. Although standard contrast angiography has been considered the diagnostic study of choice to identify pseudoaneurysms, isotope angiography has been described as an alternative method. In this study, we examined the role of 99mTc-tagged red blood cell scans in the diagnosis of traumatic pseudoaneurysm. Forty patients underwent scans; 25 scans were reported as abnormal and 15 as normal. There were no false-negative results; one scan had false-positive results (2.5%). The presence of pseudoaneurysm among the patients with abnormal scans was verified at operation in 23 of 25 patients. The one false-positive test was verified by ultrasound. All patients with normal scans were followed up for verification. Follow-up time ranged from 2 to 28 months. Radionuclide vascular flow study appears to give information similar to that of conventional angiography. With a series false-positive rate of 2.5%, the examination has a high specificity. The 99mTc-tagged red blood cell scan is a viable alternative to conventional angiography for the diagnosis of traumatic pseudoaneurysms and is associated with less radiation and morbidity. PMID- 3346954 TI - In vitro bursting strength studies of laser-welded tissue and comparison with conventional anastomosis. AB - We compared the mechanical integrity of microvascular anastomoses created with a carbon dioxide (CO2) laser with conventional suture anastomoses. Seventy rat femoral artery segments (35 lased and 35 sutured) were harvested at 1, 24, and 72 hours, and 1, 3, 6, and 12 weeks postoperatively. These segments were subjected to increasingly higher in vitro intraluminal hydrostatic pressures (bursting pressure). Conventionally sutured anastomoses exhibited significantly increased ability (p less than 0.05) to withstand greater bursting pressures than the laser welded tissue up to 3 weeks postoperatively. After the third postoperative week, the laser anastomoses demonstrated increased bursting pressures compared with the conventional anastomoses. At the end of the 12-week period both groups demonstrated an ability to withstand supraphysiologic pressures in excess of 2000 mm Hg. PMID- 3346955 TI - Polypropylene suture stresses after closure of longitudinal arteriotomy. AB - This study was performed (1) to determine the load on polypropylene (Prolene) sutures when used to close a longitudinal carotid arteriotomy and (2) to compare that load with the tensile strength of the suture material. Laboratory methods were used to determine the stress caused by pressure, the surgeon's knot, and that resulting from longitudinal extension of the sutured vessel. Results showed that the stress from the surgeon's knot accounts for more than 95% of total load on the suture, the remainder resulting from pressure and geometry. At 100 mm Hg in a 10 mm carotid artery at in situ length, 5-0 Prolene suture is loaded to 22%, 6-0 to 32%, and 7-0 to 42% of their respective breaking stresses. When the cervical spine is hyperextended, the carotid artery is stretched up to 6%. When the sutured pressurized vessel is extended 6%, 5-0 Prolene suture is loaded to 51%, 6-0 to 52%, and 7-0 to 75% of breaking stresses. These data suggest that 5-0 and 6-0 Prolene sutures should be used in preference to 7-0 sutures to close a carotid arteriotomy. PMID- 3346956 TI - Below-knee physiologic cryoanesthesia in the critically ill patient. AB - Controversy has surrounded the role of local hypothermia as a preoperative treatment in amputations of the lower extremity. A study was undertaken to determine the effectiveness of amputation under cryoanesthesia in decreasing postoperative morbidity and mortality in below-knee (BK) amputations. Of 154 BK amputations, only 91 with unreconstructable vascular disease, gangrene, or both, were included in this study. Group I consisted of 48 patients (mean age 63.9 years) who had undergone a routine BK amputation; group II consisted of 43 patients (mean age 65.7 years) who were acutely ill and too unstable to undergo a major surgical procedure. Group II patients were treated by amputation while under cryoanesthesia before any definitive operative intervention. The patients in group II were significantly (p less than 0.05) more ill preoperatively than those in group I. Group II patients had a higher prevalence of previous myocardial infarction, previous stroke, diabetes mellitus, osteomyelitis, and wet gangrene. Seventy percent of the patients in group II had three or more risk factors vs. 46% in group I. Early postoperative mortality rates did not differ significantly between groups (group I, 8%; group II, 9%); the average length of hospital stay for group I patients was 24.2 days compared with 17.7 days in group II. Group II patients sustained slightly more postoperative complications. Amputation under cryoanesthesia appears to be of value in reducing postoperative morbidity and mortality and length of hospital stay in the acutely ill patient with unreconstructable vascular disease, gangrene, or both. PMID- 3346958 TI - Does tandem lesion mean tandem risk in patients with carotid artery disease? PMID- 3346957 TI - Unusual venous thrombosis associated with protein C deficiency. AB - A patient in whom massive puerperal thrombophlebitis developed had protein C deficiency. In patients who initially have thrombosis that is unusual either in its nature or extent, investigation may, as in this case, reveal the presence of a hypercoagulable state. PMID- 3346959 TI - An improved retraction system for vascular surgical procedures. PMID- 3346960 TI - Heparin-associated thrombocytopenia and thrombosis: a serious clinical problem and potential solution. PMID- 3346961 TI - Mortality and limb loss with infected infrainguinal bypass grafts. PMID- 3346962 TI - The pathogenesis of venous ulceration: a hypothesis. PMID- 3346964 TI - AIDS around the world: analyzing complex patterns. PMID- 3346965 TI - Innovative rehabilitation programs get 'them ol' bones' walking around again. PMID- 3346963 TI - Surgical management of refractory venous stasis ulceration. AB - A 15-year experience with 27 patients, 20 to 75 years of age, with refractory venous stasis ulcers is presented. All patients had been managed with support hose, elevation, elastic wraps, Unna's paste boots, and graduated compression stockings. Because of multiple recurrences of their ulcers, the patients were offered surgical treatment to reduce the venous hypertension in the areas of ulceration. The 27 patients had 32 modified Linton procedures. Five had bilateral procedures. At the time of operation, 18 limbs had medial malleolar ulcers, five had bimalleolar ulcers, four had lateral ulcers, three had posterior ulcers, and two patients were free of ulcer. Medial incisions were used in 20 limbs, lateral incisions in six, medial and lateral incisions in three, and midposterior incisions in three. Split-thickness skin grafts were placed on six limbs the day of surgery and on 22 limbs 4 to 7 days later. Postoperative complications included deep venous thrombosis in two, partial flap necrosis in three, and cellulitis of the lower leg in three patients. Follow-up has ranged from 6 months to 10 years. During the most recent clinic visits, 21 limbs were completely healed, whereas six limbs had a recurrence of the ulcer. Five patients have been lost to follow-up. The good long-term results in 78% of the cases indicate that patients with recurrent venous stasis ulcers may receive lasting benefit from modified Linton procedures. PMID- 3346966 TI - IVF Registry notes more centers, more births, slightly improved odds. PMID- 3346967 TI - Leads from the MMWR. Condoms for prevention of sexually transmitted diseases. PMID- 3346968 TI - Leads from the MMWR. Rapid nutrition evaluation in drought-affected regions of Somalia--1987. PMID- 3346969 TI - Mad honey. PMID- 3346970 TI - The bitter herbs of Seder: more on horseradish horrors. PMID- 3346971 TI - Tobacco and cancer of the tongue in young adults. PMID- 3346972 TI - Librarians, catalogers, searchers. PMID- 3346973 TI - Generic drug substitution. PMID- 3346974 TI - Intravenous cocaine, crack, and HIV infection. PMID- 3346975 TI - The quality and influence of JAMA. PMID- 3346976 TI - Geographic variations in the use of health care services. PMID- 3346977 TI - Outbreak of hypersensitivity pneumonitis in an industrial setting. AB - Symptoms consistent with hypersensitivity pneumonitis developed in several workers in two multistory buildings in an industrial complex. A health questionnaire survey was conducted to determine the extent of the problem. Eighty seven percent of the population of 1050 employees completed the health questionnaire. Serological testing identified 152 positive precipitin reactors to the fungus Aureobasidium pullulans; 115 reactors were symptomatic. The clinical and laboratory features at the time of the acute illness and during four years of follow-up are described. The agent, A pullulans, was identified as a contaminant of the heating-cooling ventilation units containing open waterspray chambers. Control was accomplished by replacement of the ventilation systems. A secondary source of antigen was found to be corrugated cardboard. Some sensitized employees required removal from work exposure to corrugated cardboard to prevent recurrent symptoms. PMID- 3346978 TI - The stability of early specialty preferences among US medical school graduates in 1983. AB - Medical graduates in 1983 were in preclinical training when the Graduate Medical Education National Advisory Committee forecast a surplus of 70,000 physicians by 1990. Among the problems identified was the nuclear role of medical schools in affecting specialty choices. To understand this role further, the current study determined the stability and evolution of specialty preferences between the time of the Medical College Admission Test and the senior year of medical school. The study included 10,321 US medical school graduates in 1983. Eighty percent changed their specialty preference during this interval, demonstrating the substantial effects that medical schools have on specialty selection. The stability of early preferences ranged from 41% to 1%. Interest in primary care specialties declined among both men and women; interest in specialty care and supporting services increased during this five-year longitudinal study. These findings parallel shifts away from primary care among US medical school graduates in 1978 and 1983. PMID- 3346979 TI - Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study. AB - The present study of primary prevention in white men aged 40 to 64 years attempts to investigate whether a beta-blocker given as initial antihypertensive treatment would lower total mortality to a greater extent than thiazide diuretics. Patients were randomized to metoprolol (n = 1609, 8110 patient-years) or a thiazide diuretic (n = 1625, 8070 patient-years). The median follow-up time was 4.2 years. The mean dose of metoprolol was 174 mg/d, and of thiazide diuretics, 46 mg/d of hydrochlorothiazide or 4.4 mg/d of bendroflumethiazide. Identical control of blood pressure was achieved using a fixed therapeutic schedule. Total mortality was significantly lower for metoprolol than for thiazide diuretics because of fewer deaths from coronary heart disease and stroke. Total mortality was also significantly lower in smokers randomized to metoprolol. The benefit demonstrated in patients treated with metoprolol seems to have important implications for clinical practice. PMID- 3346980 TI - In-flight deaths during commercial air travel. How big is the problem? AB - Do passenger deaths occur during commercial air travel? If so, how often and from what causes? We reviewed information reported to the International Air Transport Association on in-flight deaths that occurred during commercial air travel for the eight years between 1977 and 1984. Of the 120 airlines in the International Air Transport Association, 42 carriers reported deaths during these eight years. A total of 577 in-flight deaths were recorded, for a reported average of 72 deaths per year. Deaths occurred at average rates of 0.31 per million passengers, 125 per billion passenger-kilometers, and 25.1 per million departures. The majority of those who died were men (66%, 382/577) and middle-aged (mean age, 53.8 years). Most of the individuals (77%, 399/515) reported no health problems prior to travel. Physicians aboard the aircraft offered medical assistance for 43% (247/577) of the deaths. More than half of the deaths (56%, 326/577) seemed to be related to cardiac problems. Sudden unexpected cardiac death was the cause of death in 63% (253/399) of the apparently healthy people and seems to be the major cause of death during air travel. These observations support the initiation of programs to train cabin personnel in the skills of basic cardiopulmonary resuscitation and in the use of automatic external defibrillators. PMID- 3346981 TI - Severe facial injuries to infants due to unprovoked attacks by pet ferrets. AB - Three infants were attacked by pet ferrets and sustained severe facial injuries. Two of the children had their ears bitten off and required reconstructive surgery. The attacks were unprovoked. Two of the children were asleep in their cribs when they were bitten. Although ferrets are increasingly popular pets, we believe that they are not suitable pets for families with small children. Physicians should be aware that ferrets may unpredictably injure infants and that no effective rabies vaccine for ferrets is yet available. PMID- 3346982 TI - Animals in research. PMID- 3346983 TI - A piece of my mind. Unpublishable results. PMID- 3346984 TI - Stronger laws and stiffer penalties aimed at keeping drivers safely sober. PMID- 3346985 TI - Leads from the MMWR. Progress toward achieving the national 1990 objectives for injury prevention and control. PMID- 3346987 TI - Building-associated risk of febrile acute respiratory diseases in Army trainees. AB - Airborne transmission of infectious agents and associations of indoor air pollutants with respiratory illnesses are well documented. We hypothesized that energy conservation measures that tighten buildings also increase risks of respiratory infection among building occupants. At four Army training centers during a 47-month period, incidence rates of febrile acute respiratory disease were compared between basic trainees in modern (energy-efficient design and construction) and old barracks. Rates of febrile acute respiratory disease were significantly higher among trainees in modern barracks (adjusted relative risk estimate, 1.51; 95% confidence interval, 1.46 to 1.56), and relative risks were consistent at the four centers. These results support the hypothesis that tight buildings with closed ventilation systems significantly increase risks of respiratory-transmitted infection among congregated, immunologically susceptible occupants. PMID- 3346986 TI - It's over, Debbie. PMID- 3346988 TI - Persistence of reduction in blood pressure and mortality of participants in the Hypertension Detection and Follow-up Program. Hypertension Detection and Follow up Program Cooperative Group. AB - The Hypertension Detection and Follow-up Program (HDFP) previously described a significant reduction in five-year, all-cause mortality in its intensively treated stepped care (SC) group relative to its referred care (RC) control group. At the time this finding was described, a proportion of the SC cohort had been treated for periods as long as 6.7 years, but comparable RC and SC mortality data beyond five years were not available. These data, which are described herein, indicate that the 6.7-year life-table mortality rates were 95.1/1000 participants for SC vs 116.3/1000 participants for RC, a larger mortality difference than was observed at five years. This favorable finding for SC extended to all major subgroups, including white women and those aged 30 to 49 years at trial entry. Six months after the close of the treatment trial, a two-year posttrial surveillance study, which extended mortality follow-up to 8.3 years, was conducted. The posttrial use of antihypertensive medication declined in SC and increased in RC participants so that by the end of the posttrial period, there was little difference in the percentages of SC and RC participants taking medication. Control of blood pressure, indicated by mean diastolic blood pressure and by percent of participants with a pressure of 90 mm Hg or less, was slightly better for SC than for RC participants (SC group, 86.5 mm Hg and 68% controlled; RC group, 87.8 mm Hg and 62% controlled). The absolute mortality advantage found at 6.7 years persisted and increased throughout the posttrial period of follow-up despite discontinuation of the formal SC therapy program. It is postulated that regression of hypertensive end-organ changes brought about by the more effective SC treatment caused this favorable outcome. PMID- 3346989 TI - 'Doctors must not kill'. PMID- 3346990 TI - Debbie's dying: mercy killing and the good death. PMID- 3346991 TI - 'It's over, Debbie' and the euthanasia debate. PMID- 3346992 TI - A piece of my mind. On deeper reflection. PMID- 3346993 TI - Diagnostic and therapeutic technology assessment. BCG immunotherapy in bladder cancer: a reassessment. AB - The DATTA panelists considered BCG immunotherapy to be efficacious in reducing recurrences of transitional cell carcinoma of the bladder. It has reduced recurrences in some patients in whom chemotherapeutic agents have failed, and in recent trials it has performed better than doxorubicin in preventing recurrences and in treatment of CIS. The DATTA panelists urged close evaluation of patients undergoing BCG therapy to guarantee that the tumor does not progress during treatment. Adverse reactions to BCG were not considered serious enough to jeopardize its use. PMID- 3346994 TI - [Long-term follow-up after tumorectomy and irradiation for breast cancer]. AB - From 1968 to 1976, 31 patients underwent breast conservation surgery (tumorectomy) and irradiation. A review of the available pathologic slides has revealed that 11 of that number had definite breast cancer. Of these 11 patients, three experienced a relapse, one with local recurrence only, and two with distant metastasis, though one of these two also had a local recurrence. The patient manifesting a local recurrence only was salvaged by a mastectomy, while the other two with distant metastases have died. Survival and disease-free survival in these 11 patients were at least equal to the results of other Japanese patients of the same ages and stages who had undergone a halsted operation during the same period. As for the other 20 patients, either their pathologic slides were not available, or their diagnosis was equivocal or benign. None suffered a relapse. Cosmetic results were excellent in most patients, and there were no second malignancies in the treatment volume. PMID- 3346996 TI - [Observations on the growth rate of polypoid type gastric cancers with doubling times based on a retrospective roentgenological study]. AB - For the purpose of estimating the growth rate, 11 cases of polypoid type gastric cancer have been studied. The mean doubling time was found to be 16.6 months in early cases, and 7.6 months in advanced cases. There were two groups with different growth rates in polypoid type gastric cancer. However, from a study of a case growing faster according to the extension of tumor, it is suggested that the difference of the growth rate between the two groups may have resulted from a discrepancy of when the observation began. PMID- 3346995 TI - [A cytologic diagnosis of breast secretions--application of cytology to the mass survey of breast cancer]. AB - From January 1982 to March 1987, an exfoliative cytological examination of abnormal nipple discharge was carried out on 790 patients. Of 22 histologically confirmed mammary carcinomas, 7 cases (31.8%) were diagnosed as positive by conventional cytologic techniques. By using the concentration method, in which the nipple secretion was collected in a series of testings that lasted 3 to 5 days and stored in a glass tube containing a fixative, the diagnostic accuracy was seen to increase significantly and 9 out of 15 malignant cases (60.0%) were accurately diagnosed as having cancer. Moreover, all 5 cases without any palpable mass were found to be positive by the smears made by this procedure. PMID- 3346997 TI - [A case report of carcinoid of the rectum coexisting with adenocarcinoma in a single lesion]. AB - A 69-year-old female, chiefly complaining of diarrhea, was admitted to the Toyama Medical & Pharmaceutical University Hospital. A barium enema and an endoscopic examination revealed a villous adenocarcinoma of the rectum. Computerized tomography disclosed multiple metastatic lesions in the liver. She underwent an amptatio recti and an intra-arterial cannulation of the common hepatic artery in order to administer anticancer agents. Gross findings of the resected specimen showed villous adenocarcinoma containing a small ulcerated lesion. Histologic findings of this lesion revealed a collision neoplasm containing both an adenocarcinoma and a carcinoid with no obvious transitional region between the two lesions. The type D carcinoid, determined according to Soga's histologic classification, showed positive argyrophil granules but no argentaffin granules in the cytoplasm. The electron-microscopic findings of the carcinoid revealed small electron-dense endocrine granules measuring about 150 approximately 300 nm in diameter. The woman died 4 months after this operation. PMID- 3346998 TI - [Carcinoid tumor of the ileum with intestinal tuberculosis--report of a case]. AB - A 65-year-old woman visited our hospital, complaining dizziness and abdominal pain. Positive fecal occur blood and an iron-deficiency anemia were found. An investigation of the GI tract was performed, and enteroclysis revealed three stenotic lesions in the ileum, the most distal one having an irregular edge. A superior mesenteric angiogram showed tumor stain and encasement in the ileal region. On laparotomy, a large tumor and multiple stenosis were found in the ileum. Histological examination of the resected specimen confirmed the diagnosis of a carcinoid tumor and healed tuberculosis of the ileum. PMID- 3346999 TI - [Multilocular epidermoid cyst of the spleen--report of a case observed with an electron microscope]. AB - A 27-year-old female, complaining of left hypochondralgia, underwent a splenectomy and a partial pancreatectomy. The spleen, 18.5 x 14 x 6 cm in size and weighing 1060 g., was occupied by a large multicystic mass. The cystic cavities contained turbid chocolate-colored fluid or a yellowish creamy substance. The cysts varied in size and were lined by stratified squamous epithelium. By means of an electron microscope, a few Langer hans cells were seen in the stratified squamous epithelium, but melanocytes and Merkel cells were not noticed. Twenty-eight cases of splenic epidermoid cysts reported in Japan are briefly reviewed. PMID- 3347000 TI - [Superior vena cava syndrome associated with carcinoma of the uterine cervix- report of two cases]. AB - Superior vena cava syndrome (SVCS) is a very rare complication in patients with a gynecologic malignancy. Only 4 cases have been reported in the English literature thus far and, to our knowledge, no such case has been reported in the Japanese literature. We have encountered two cases of SVCS in patients with cervical cancer. In case 1, the SVCS developed secondarily to a metastasis of the cervical cancer to the lungs and mediastinum. In case 2, the cause of the SVCS had been presumed to be due to metastatic cervical cancer, however on autopsy, it turned out to be due to a coexistent malignant lymphoma. PMID- 3347001 TI - Nursing care of the PMS client. PMID- 3347002 TI - Participation in NLRB rulemaking. PMID- 3347003 TI - The public cost of adolescent pregnancy in Kansas. PMID- 3347004 TI - Cyclosporin-associated nephropathy in patients with autoimmune diseases. AB - Renal biopsy specimens were evaluated from patients with different autoimmune diseases treated with cyclosporin (CyA). Ten biopsies were done before CyA, 10 biopsies after low-dose (less than 7.5 mg/kg/day, initial dose or mean daily dose within the first month, respectively), and 9 after high-dose (greater than 7.5 mg/kg/day) treatment. Definite chronic CyA nephrotoxicity (cyclosporin-associated arteriolopathy and/or interstitial fibrosis striped form with tubular atrophy) was only present in the initial high-dose group. In this group a significant serum creatinine increase was noted and 8 of the 9 patients were hypertensive. No significant correlation was found between the severity of morphologic lesions and the mean daily dose during total treatment, cumulative dose, and duration of therapy. The morphologic changes in the low-dose group did not differ from the control biopsy specimens before CyA treatment. Based on these results, it can be concluded that major nephrotoxicity can be avoided by initial low CyA doses. PMID- 3347005 TI - Capillary rarefaction characteristic of the skeletal muscle of hypertensive patients. AB - There is evidence that the rarefaction of the capillary bed is typical for the skeletal muscle of spontaneously hypertensive rats. We were therefore interested to learn whether there is also a rarefaction in skeletal muscle of human hypertensives. The number of capillaries was morphometrically analysed and counted in the quadriceps and the pectoralis major muscles of human normotensives (n = 12) and hypertensives (n = 15). The clinical diagnosis and certain pathological criteria, such as blood pressure (with or without antihypertensive therapy), heart weight, left ventricular wall thickness, the state of kidney arterioles and brain, and heart vessels, were used to classify the patients into two groups. The dissected tissue samples were prepared according to the GMA method and the capillary numbers per area were counted using light microscopy (250 x). The quadriceps muscle had a capillary density (per 2.5 mm2) of 442 +/- 51 in normotensives and 277 +/- 41 in hypertensive patients; in the pectoralis major muscle we counted 477 +/- 30 in controls and 232 +/- 28 in hypertensives. The rarefaction in the quadriceps muscle ranged by about 37%, in the pectoralis major muscle by about 51%. It is suggested that the reduction of the capillary surface area caused by the capillary rarefaction reduces the transcapillary fluid exchange and in that way prevents an overperfusion of the terminal vascular bed. PMID- 3347007 TI - [Reocclusion following successful thrombolytic therapy in acute myocardial infarct]. AB - Following successful reperfusion of the previously occluded coronary artery in acute myocardial infarction, reocclusion remains an at least partially unsolved problem. The literature reports figures between 10 and 30%. In the present study, 130 out of 543 patients with successful thrombolysis by means of intracoronary streptokinase underwent a follow-up angiography at the 3rd day (106/130, 80%) and/or 6 months (76/130, 59%) after the acute intervention. During the observation period, neither PTCA nor bypass surgery were performed. Reocclusion could be documented in 5.5% of patients at the early stage, and in 25.0% half a year later. In more than 75% of patients, who presented with a reoccluded infarct related artery, clinical evidence of reinfarction had been recorded during the follow-up period. PMID- 3347006 TI - Intraoperative localization of malignant pheochromocytoma by 123-I metaiodobenzylguanidine single probe measurement. AB - Metaiodobenzylguanidine (MIBG) imaging is a well-established method for locating intra- and extraadrenal pheochromocytomas. We investigated whether preoperative injection of 123-I-MIBG might be useful for intraoperative staging of chromaffine tumor cells. This was performed in a 46-year-old patient in whom the diagnosis of a malignant pheochromocytoma had been established by 123-I-MIBG imaging and enhanced catecholamine secretion. The rationale for intraoperative staging in this patient was a discrepancy between computed tomography (CI) of the abdomen and the radionuclide imaging, because scintigraphy revealed a mass with MIBG uptake in the right lower abdomen that could not be visualized by CT. We thus applied a preoperative dose of 4 mCi 123-I-MIBG and determined tissue activity by direct organ measurement. A right abdominal mass was thus identified with an activity of 10 x 10(4) impulses/s as compared to normal tissue (15 x 10(2)). The left-sided tumor was found to be identified correctly by prior CT and MIBG imaging. We thus conclude that intraoperative application of this single probe measurement might help to identify chromaffine tumor cells that have not been located fully by CT. PMID- 3347008 TI - [Which laboratory parameters are useful and necessary in fibrinolytic therapy?]. AB - Even sophisticated assays of blood coagulation and of fibrinolysis cannot predict the clinical success of thrombolytic therapy, nor can they prevent bleeding complications. Nevertheless, some laboratory monitoring is indicated before thrombolytic therapy to rule out contraindications, and it should also be performed during thrombolytic therapy as a guideline for substitution therapy in case of bleeding and for control of concommitant or subsequent anticoagulant therapy. An initial assessment should comprise the assay of fibrinogen, prothrombin time, partial thromboplastin time, and a platelet count. One to two hours after initiation of thrombolytic therapy and at its end (as well as at 12 hourly intervals in between in prolonged courses of thrombolytic therapy), a fibrinogen assay and a test that is sensitive to fibrin(ogen) degradation products (e.g. thrombin time, reptilase time, prothrombin time) should be performed. PMID- 3347009 TI - Depletion of serum holotranscobalamin II. An early sign of negative vitamin B12 balance. AB - Preferential depletion of corrinoids on transcobalamin II (i.e., sharply reduced holo transcobalamin II (TC II)) occurs early in vitamin B12 deficiency. We measured corrinoids (Cor) and cobalamins (Cbl) on transcobalamins I and III (TC I + III) and on TC II. We also measured the unsaturated B12 binding capacities of transcobalamin I and III and TC II in serum from patients with B12 deficiency (N = 5) (with or without concurrent folate deficiency), with pernicious anemia in remission (N = 7) (1 month after therapy), and in several control groups including healthy volunteers (N = 6), hematologically normal elderly hospitalized patients (N = 5), and non-B12 nonfolate deficient anemic elderly hospitalized volunteers (N = 5). In B12 deficient patients, Cor = 177 +/- 92 pg/ml, Cbl = 56 +/- 20 pg/ml, TC II Cor = 1.0 +/- 2.2 pg/ml, and TC II Cbl = 4.4 +/- 4.9 pg/ml in contrast to pooled controls with Cor = 730 +/- 229, Cbl = 523 +/- 198, TC II Cor = 100 +/- 84, and TC II Cbl = 88 +/- 70 (all values expressed in picograms/milliliters). In pernicious anemia in remission, Cor = 505 +/- 138, Cbl = 294 +/- 77, TC II Cor = 80 +/- 31 and TC II Cbl = 37 +/- 36. TC II unsaturated B12 binding capacity was significantly higher in B12 deficient patients than in pooled controls. These data support that: (a) holo TC II is sharply depleted in untreated B12 deficiency; (b) normally, the only Cor on TC II are cobalamins; (c) in treated pernicious anemia, TC II appears to also bind non-cobalamin corrinoids; (d) continued malabsorption of vitamin B12 may result in reduced B12 on TC II within a month after the last parenteral therapy with 1000 micrograms of cyanocobalamin, and (e) TC II UBBC rises as B12 deficiency is developing. Further investigation is required for definitive delineation of whether sharply reduced Cor on TC II in untreated B12 deficiency can diagnose "true" B12 deficiency, in view of false positive or false negative results which occur in all serum B12 assays. PMID- 3347010 TI - Distribution of estrogen receptors in various cell types of normal, hyperplastic, and neoplastic human endometrial tissues. AB - To facilitate our understanding of estrogen participating in the genesis of human endometrial hyperplasia and carcinoma and the influence of the surrounding mesenchyme in their development, we assayed estrogen receptors in the epithelium and stroma of various human endometrial tissues by immunocytochemistry. The receptors were localized in fresh frozen sections using the ER-ICA kits (Abbott Laboratories, North Chicago, Illinois). The receptor content was highest in the proliferative endometrium and decreased gradually throughout the postovulatory phase of the menstrual cycle in both the epithelium and the stroma and this occurred more rapidly in the stroma. Estrogen receptor content was high in both the epithelium and the stroma of hyperplasia and was thus similar to that of the proliferative endometrium, the receptor content was low in the epithelium of endometrial intraepithelial neoplasia (hyperplasia with cytologic atypia) closely resembling that of carcinoma. In carcinomas there was a heterogenous distribution of estrogen receptors both in the epithelium and the stroma, but in general, the receptor content was low as compared with normal proliferative or hyperplastic endometrium; however, in selected cases the content of estrogen receptor in the stroma was high, despite the lack of receptors in the epithelium. PMID- 3347011 TI - The State Planning Committee for Health Education in Ohio. AB - The State Planning Committee for Health Education in Ohio (SPCHEO) developed and applied a model for improving comprehensive school health programs that can be adapted and facilitated by health education coalitions or professional associations in any state. The model is based on development of a well-rounded school-community health team. SPCHEO members who assume the role of team organizers facilitate a planning process that includes building a school community health team, assessing and analyzing school health instruction, services, environment, and administration, establishing priorities, goals, and objectives, identifying resources, implementing strategies, and evaluation. The model stimulates action toward improved comprehensive school health programs. A new adaptation of the model is being explored to expand its impact. PMID- 3347012 TI - Applicability of the Parcel-Meyer Children's Health Locus of Control Scale. AB - Locus of control has emerged as an important outcome variable in many health education programs. This study evaluated one instrument designed to measure this construct. Responses to the Parcel-Meyer Children's Health Locus of Control Scale from two groups of sixth grade students were collected to consider fit of the items to the underlying theoretical model and invariance of the finding from different populations. Factor structures from the two groups did not match one another or Levenson's model. Several items did not have any major loadings. Lack of fit and variance of the results is discussed in terms of the items being inappropriate for this age group, since seven and nine of the 20 items had almost no item variance with 90% or more of students responding with the internal answer. Revision of the scale is recommended. PMID- 3347014 TI - Drug abuse hysteria: the challenge of keeping perspective. PMID- 3347013 TI - Reliability of health knowledge measurement in very young children. AB - This study documented reliability of a picture identification instrument and determined its utility with young children in selected preschool programs. Three hundred eleven children, ages three-five, were selected from formal early childhood education programs in three states. A comprehensive health knowledge instrument, consisting of 30 items, was administered to all children, and a retest was administered two weeks later to a 20% randomly selected subsample. Data analysis included reliability assessments and systematic modification of the instrument. Pearson's Product Moment Correlation and Kuder Richardson 21 analyses indicated the instrument is reliable when administered individually to children ages three-five. The authors recommended this instrument, or a similar picture identification instrument, be used to assess comprehensive health knowledge. PMID- 3347015 TI - Writing activities in the health education classroom. PMID- 3347016 TI - A school program to reduce dental caries. PMID- 3347017 TI - Curriculum emphasis cannot omit liberal arts. PMID- 3347018 TI - Lyme disease treatment needs further preventive measures. PMID- 3347019 TI - Mechanical responses of tendons to repeated extensions and wait periods. AB - Tendon specimens were repeatedly extended to peak strains of either 2, 3, 4, or 6 percent. During the three 1800 s (30 min.) periods of cyclic extension, the peak loads relaxed with decreases in hysteresis and increases in slack strain. During the two 1800 s wait periods of no extension, the specimens recovered with increases in peak load and hysteresis and decreases in slack strain. However, the recovery during the wait periods was eradicated in the first few subsequent extensions and the relaxation continued as if there were no 1800 s wait periods. Stress-strain responses were well fit with power relations. PMID- 3347020 TI - A theory of blood flow in skeletal muscle. AB - A theoretical analysis of blood flow in the microcirculation of skeletal muscle is provided. The flow in the microvessels of this organ is quasi steady and has a very low Reynolds number. The blood is non-Newtonian and the blood vessels are distensible with viscoelastic properties. A formulation of the problem is provided using a viscoelastic model for the vessel wall which was recently derived from measurements in the rat spinotrapezius muscle (Skalak and Schmid Schonbein, 1986b). Closed form solutions are derived for several physiologically important cases, such as perfusion at steady state, transient and oscillatory flows. The results show that resting skeletal muscle has, over a wide range of perfusion pressures an almost linear pressure-flow curve. At low flow it exhibits nonlinearities. Vessel distensibility and the non-Newtonian properties of blood both have a strong influence on the shape of the pressure-flow curve. During oscillatory flow the muscle exhibits hysteresis. The theoretical results are in qualitative agreement with experimental observations. PMID- 3347022 TI - Smoothing noisy data using dynamic programming and generalized cross-validation. AB - Smoothing and differentiation of noisy data using spline functions requires the selection of an unknown smoothing parameter. The method of generalized cross validation provides an excellent estimate of the smoothing parameter from the data itself even when the amount of noise associated with the data is unknown. In the present model only a single smoothing parameter must be obtained, but in a more general context the number may be larger. In an earlier work, smoothing of the data was accomplished by solving a minimization problem using the technique of dynamic programming. This paper shows how the computations required by generalized cross-validation can be performed as a simple extension of the dynamic programming formulas. The results of numerical experiments are also included. PMID- 3347021 TI - Passive deformation analysis of human leukocytes. AB - The following analysis presents an experimental and theoretical study of the passive viscoelastic behavior of human leukocytes. Individual neutrophils in EDTA were observed both during their partial aspiration into a small micropipette and after expulsion from a large micropipette where the cell had been totally aspirated and deformed into a sausage shape. To analyze the data, a passive model of leukocyte rheology has been developed consisting of a cortical shell containing a Maxwell fluid which describes the average properties of the cell cytoplasm. The cortical shell represents a crosslinked actin layer near the surface of the cell and is assumed to be under pre-stressed tension. This model can reproduce the results of experiments using micropipette for both short-time small deformation and slow recovery data after large deformation. In addition, a finite element scheme has been established for the same model which shows close agreement with the analytical solution. PMID- 3347023 TI - A stress compatible finite element for implant/cement interface analyses. AB - A new finite element has been developed to enforce normal and shear stress continuity at bimaterial interface points in order to alleviate the problem of high stress discontinuity predictions by the conventional displacement finite element method. The proposed element is based on a five node isoparametric quadrilateral element where the fifth node is located at the interface boundary of the element. A series of validation tests have been carried out to assess the correctness of the stress distribution obtained by the new element at interfaces of highly dissimilar materials. The results of the tests are compared to analytical solutions and to results from convergence studies performed by the conventional finite element method (SAP-IV). Overall, the proposed element has been demonstrated to have a very satisfactory degree of reliability, especially in view of the observed inability of the conventional method to yield interpretable interface stress values for most cases analyzed. Finally, the new interface element has been applied to the analysis of an axisymmetric model of the knee tibial implant. The superiority of the proposed element over the conventional one has been demonstrated in this case by a convergence study. PMID- 3347024 TI - Nonlinear incompressible finite element for simulating loading of cardiac tissue- Part I: Two dimensional formulation for thin myocardial strips. AB - A two-dimensional incompressible plane-stress finite element is formulated for the simulation of the passive-state mechanics of thin myocardial strips. The formulation employs a total Lagrangian and materially nonlinear approach, being based on a recently proposed structural material law, which is derived from the histological composition of the tissue. The ensuing finite element allows to demonstrate the mechanical properties of a single myocardial layer containing uniformly directed fibers by simulating various loading cases such as tension, compression and shear. The results of these cases show that the fiber direction is considerably stiffer than the cross-fiber direction, that there is significant coupling between these two directions, and that the shear stiffness of the tissue is lower than its tensile and compressive stiffness. PMID- 3347025 TI - Nonlinear incompressible finite element for simulating loading of cardiac tissue- Part II: Three dimensional formulation for thick ventricular wall segments. AB - A three dimensional incompressible and geometrically as well as materially nonlinear finite element is formulated for future implementation in models of cardiac mechanics. The stress-strain relations in the finite element are derived from a recently proposed constitutive law which is based on the histological composition of the myocardium. The finite element is formulated for large deformations and considers incompressibility by introducing the hydrostatic pressure as an additional variable. The results of passive loading cases simulated by this element allow to analyze the mechanical properties of ventricular wall segments, the main of which are that the circumferential direction is stiffer than the longitudinal one, that its shear stiffness is considerably lower than its tensile and compressive stiffness and that, due to its mechanically prominent role, the collagenous matrix may affect the myocardial perfusion. PMID- 3347026 TI - An experimental approach to evaluate the dynamic behavior of the human knee. AB - An experimental approach for an in vitro investigation of some aspects of dynamic force transmission through the human knee joint is presented. Essentially, the behavior of the joint was analyzed by measuring the responses to low level random excitation of the tibia while the femur was clamped. A global equilibrium position of the joint was attained by exerting static forces on the tibia via three tendinous muscle attachments. The responses to the applied dynamic loads were measured using a multi-channel dynamic measuring system and quantified by means of transfer function analysis techniques. Some preliminary experimental results are presented to illustrate the effects of variation of the direction and the magnitude of the applied dynamic and static loads. PMID- 3347027 TI - On the generalization of the Weinbaum-Jiji bioheat equation to microvessels of unequal size; the relation between the near field and local average tissue temperatures. AB - The extensive series of experiments reported in Lemons et al. [1] show that measureable local tissue temperature fluctuations are observed primarily in the vicinity of the 100-500 micron countercurrent vessels of the microcirculation and thus strongly support the basic hypothesis in the new bioheat equation of Weinbaum and Jiji [2] that these countercurrent microvessels are the principal determinants of local blood-tissue heat transfer. However, the detailed temperature profiles in the vicinity of these vessels indicate that large asymmetries in the local temperature field can result from the significant differences in size between the countercurrent artery and vein. Using the superposition techniques of Baish et al. [9], the paper first presents a solution to the classic problem of an unequal countercurrent heat exchanger with heat loss to the far field. This solution is then used to generalize the Weinbaum-Jiji bioheat equation and the conductivity tensor that appears in this equation to vessels of unequal size. An asymptotic analysis has also been developed to elucidate the relationship between the near field temperature of the artery-vein pair and the local average tissue temperature. This analysis is used to rigorously prove the closure approximation relating the local arterial-venous temperature difference and the mean tissue temperature gradient which had been derived in [2] using a more heuristic approach. PMID- 3347028 TI - Zero-stress states of arteries. AB - The no-load configuration of a living organ is, in general, not the zero-stress state. The difference can be revealed by cutting up an unloaded organ to such an extent that the stress becomes zero in the tissue everywhere. For the aorta, it is shown that the configuration of the zero-stress state differs considerably from being a cylindrical tube. It is, in fact, an open sector with opening angles varying along the arterial tree. This article presents data on the zero-stress state in the arteries of the rat in normal condition. PMID- 3347029 TI - Biomechanical analysis of manual lifting tasks. PMID- 3347030 TI - Maximum length sequence applied to the measurement of brainstem auditory evoked responses. AB - An evoked response may be assumed to consist of synchronous electrical activities of groups of neurons in response to a stimulus. Unfortunately, this response is usually weak and often masked by the background EEG activity generated spontaneously by the brain. In order to extract the embedded evoked response we have employed the theory of maximum length sequence, assuming only a temporal linearity of the system from which measurements are taken. The technique has been applied successfully with the aid of a microcomputer. The system also supports the same measurement by a conventional averaging technique. The results of the two are compared, indicating the advantages of the maximum length technique: improved signal-to-noise ratio, repeatability and speed. PMID- 3347031 TI - High resolution ECG analysis by an improved signal averaging method and comparison with a beat-to-beat approach. AB - The aim of this paper is to describe the analysis of a high resolution ECG recorded from the body surface. Standard signal averaging techniques are improved by using a new time delay estimation method which leads to a better alignment accuracy of P and T waves. A second method uses adaptive identification to achieve a beat by beat fine ECG estimation. Information provided by the two methods allows a better interpretation of low and very low level signals. PMID- 3347033 TI - High-resolution alignment of action potential waveforms using cubic spline interpolation. AB - A cubic spline interpolation technique is applied to the problem of aligning action potential waveforms. Interpolation is an attractive alternative to sampling at many times the Nyquist rate in order to reduce errors caused by asynchronous sampling of rapidly changing waveforms. Alignment is achieved by locating the peak of the interpolated waveform, which can be found by solving a quadratic equation. The waveform is then reconstructed for comparison with existing templates. The technique was tested using simulated noisy, randomly arriving waveforms, the interpolated signal and alignment time errors being computed as functions of the signal/noise ratio. The spline technique is superior in accuracy to sampling at eight-times the Nyquist rate and is comparable to a Fourier-transform-based interpolation algorithm. It is computationally efficient, requiring approximately five multiplications per sample point. The interpolation concept is extended to the principal component technique for separation of action potential waveforms. The energy function is interpolated and used to align the waveforms, after which the interpolated coefficients can be used for high speed classification. The technique shows an improvement in both alignment error and effective signal/noise ratio in comparison with sampling or interpolation to a voltage peak. PMID- 3347032 TI - On-line measurement of muscle fibre conduction velocity: analysis and optimization of performance. AB - Measurement of the average muscle fibre conduction velocity from surface electromyographic signals has important applications in the study of muscle fatigue and in ergonomics. In this paper, a two-channel hardware polarity correlator (which estimates 256 correlation coefficients per channel at a sampling rate of 18.58 kHz) and a specially designed surface electrode unit, are used to investigate various factors affecting the measurement reliability: electrode dimensions; EMG preprocessing to make the estimated correlation function more suitable for time delay measurement; and the manner in which velocity estimates, measured simultaneously from two different sections of the same muscle, are related. All the tests were performed on the biceps brachii when under medium tension; some tests involved tensions which led to muscle fatigue. Results showed that smaller electrode dimensions (i.e. smaller electrode units) and EMG preprocessing to increase its effective bandwidth, give more reliable measurements. Further, it was found that the estimated mean velocity is dependent on the location of the electrode unit on the muscle, and that at certain locations no reliable estimates can be obtained. The preliminary results obtained with muscle fatigue indicate that the estimated conduction velocity decreases, but not uniformly, across the muscle. PMID- 3347034 TI - The nature of biotechnology. AB - This review introduces the multidisciplinary subject of biotechnology and the exploitation of the 'biomolecule'. The author describes practical applications of micro-organisms and biologically derived molecules. Some of these processes have been known for many years but recent developments have led to very rapid expansion of understanding and knowledge of the subject. Areas of the technology discussed include monoclonal antibodies, gene manipulation, enzymes, cell cultures, biosensors and biological processing products. PMID- 3347035 TI - Model to characterize strain generated potentials in bone. AB - A model has been developed to characterize the strain generated potentials (SGPs) in bone. The model relates the SGP signal to the rotation (reorientation) of the spontaneous dipoles of bone in response to mechanical deformation. The effects of bone structural conditions and the measuring circuitry on the recorded potential are both accounted for by the model. PMID- 3347036 TI - Role of stem design and material on stress distributions in cemented total hip replacement. AB - The risk of fatigue fractures of the femoral stem in a cemented total hip arthroplasty can be minimized by either increasing the stem cross-section and/or using a very high strength alloy. The object of this study was to compare important mechanical characteristics of five selected stem designs, differing in configuration and material (stainless steel, cast chrome cobalt alloy, nickel based alloy and titanium alloy). The stain pattern on the stem was analysed in a 3-point-bending jig and also after cementing it into cadaver femurs. Regardless of stem type or test method, the typical tensile stress distribution on the lateral stem was a bell shaped curve. For the cobalt-chrome and stainless steel stems, the larger the stem the lower were the stem stresses and the stress gradient, and the higher was the factor of safety. However, the factor of safety was increased even further by the use of super alloys such as MP35N and Ti6Al4V. In addition, Ti6Al4V alloy allowed the use of larger and stronger stems without the extra penalty of rigidity, which was enforced by either the steel or cobalt based alloy. PMID- 3347037 TI - Design and performance of a fracture monitoring transducer. AB - The answer to the question, 'when is a fracture healed?' is not simple, since the healing process is progressive and it is not possible to specify a time when the fracture can be said to have healed. In the past the assessment of fracture healing has, in the main, been subjective, relying upon the skill of the interpreter. A more objective method would be an advantage for many reasons, and since the bone is intended to be load bearing it is reasonable to assess healing by measuring the mechanical integrity of the bone. To do this a 'clamp on' transducer has been developed which, when fitted to the support column of an external fixator, enables the stiffness of a fracture to be determined during the healing process. Over the past 6 years this system has been used for both clinical and research work. It has enabled various forms of treatment to be evaluated in terms of 'rate of healing' and it also indicates the safe point at which the fixator can be removed. PMID- 3347038 TI - Drug test chamber: a titanium implant for administration of biochemical agents to a standardized bone callus in situ. AB - A titanium implant in which a conduit is gradually filled with ingrowing bone (the Bone Harvest Chamber) has been modified to allow continuous local treatment of the conduit tissue with biochemical agents. Implants were inserted bilaterally in rabbit tibiae. The tissue content of the bone ingrowth conduits was studied with histology, 99mTc-MDP scintimetry and measurements of total calcium content. Bone was formed in the conduit by endochondral formation starting at both ends and continuing until fusion in the middle. After 2 weeks the bone had not yet met in the middle where fibrous tissue was seen. In eight animals 3H-proline was applied via one of the chambers, with the contralateral chamber as a saline treated control. The collagen of the harvested tissue from the 3H-proline treated side had a 3H-hydroxyproline content 1000 times greater than had the control side. The 'drug test chamber' makes possible the study of local effects of drugs on healing of mature bone in vivo. PMID- 3347039 TI - Physiological profile during venovenous perfusion in dogs using a polypropylene membrane lung with secondary flows. AB - Venovenous perfusion has been conducted in 12 healthy dogs to examine carbon dioxide (CO2) transfer and haemocompatibility over 9 h during total extracorporeal CO2 removal using a microporous polypropylene membrane lung with secondary flows in the blood channel. The anaesthetized animals were maintained normocapnic by including CO2 in the inspired gases. The CO2 removal was achieved using 0.631 m2 of active membrane, at a pulsatile Reynolds number of 50, and a CO2 extraction from blood of 17.8 ml (STP) dl-1. Gas exchange remained constant during the perfusions. Several aspects of our results suggest that the haemocompatibility of a system of the kind used here is at least as favourable as that of a steady flow device using a continuous silicone rubber membrane of equivalent gas transfer capability. PMID- 3347040 TI - Circumferential and longitudinal viscoelasticity of human iliac arterial segments in vitro. AB - A random noise technique was used to measure the circumferential and longitudinal dynamic elasticity of human common iliac arteries in vitro. For circumferential measurements the frequency ranged from 0.016 to 20 Hz; the phase lag of diameter behind pressure was found to be almost constant (about 5 degrees) and the Young's modulus of elasticity to increase rapidly at first and then more gradually beyond 1-2 Hz. Somewhat similar results were obtained for longitudinal elasticity. Arterial segments were found to be anisotropic when kept at in vivo length and under normal distending pressure. PMID- 3347041 TI - New high-frequency catheter technique for His bundle ablation in dogs. AB - A new method is presented for the production of complete atrioventricular heart block. It consists of a special catheter, which is inserted into the right atrium via a femoral vein and positioned in the region of the His bundle for His bundle potential recording. Production of heart block is achieved by a high frequency current pulse from an electrocautery unit. PMID- 3347042 TI - Estrogen and antiestrogen interaction with estrogen receptor of MCF-7 cells- relationship between processing and estrogenicity. AB - Overnight preincubation of MCF-7 cells with 2 x 10(-10) M estradiol (E2) produces a dramatic reduction of their specific [3H]E2 binding capacity. Scatchard plot analysis revealed that this loss of estrogen receptor (ER) concentration, usually termed "processing", occurs without any significant modification of binding properties of the unprocessed receptors. Direct measurement of ER (ER-EIA from Abbott) gave residual receptor concentrations close to those established by binding assay indicating that processing involves the loss of at least one epitope other than the steroid binding site. Incubation with increasing amounts of E2 (0.1 to 5 x 10(-10) M) resulted in an increasing reduction of binding capacity indicating that the extent of processing is associated with the hormone concentration. Steroidal estrogens other than E2 as well as antiestrogens of the triphenylethylene category behaved similarly in this regard although the latter compounds usually acted only when at higher concentrations. The processing capacity of a large series of ligands was compared with the corresponding binding affinity for ER as assessed by classical competitive inhibition of [3H]E2 binding in both cytosol and whole cells. For steroidal estrogens, a large spectrum of concordant values was found which correlated with the known uterotrophic activity of the compounds. On the contrary, weak estrogen and antiestrogens of the triphenylethylene category displayed low processing capacities which were in the order of magnitude of the binding affinities established in whole cells; these values were considerably lower than the corresponding values measured in the cytosol. These observations are consistent with the concept that the capacity of a ligand to process ER is related to its agonistic activity. They also support our hypothesis (J. steroid Biochem. 25 (1986) 677-682) that assessment of the ability of a ligand to inhibit the binding of [3H]E2 in whole cells provides an estimate of its agonistic activity, an estimate which can not be established in the corresponding cytosol assay. PMID- 3347043 TI - Estimation by gas chromatography-mass spectrometry with selected ion monitoring of urinary excretion rates of 3 alpha-androstanediol during/after i.v. administration of 13C-labelled testosterone in man. AB - To study in vivo the conversion of testosterone (T) into its metabolites, dihydro testosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta diol (3 alpha-Diol) the urinary excretion rates of these steroids were determined by mass spectrometry in 6 healthy men during/after the i.v. infusion (t = 4 h) of 20 mg [13C]testosterone. In addition, plasma concentrations of T, DHT and 3 alpha-Diol were determined by radioimmunoassay. During steady state conditions at the end of the 4-h infusion of [13C]T the increase in the plasma concentrations of T from, basal, 405 +/- 140 ng/dl to 4205 +/- 804 ng/dl was paralleled by an increase in the plasma concentrations of DHT to 106.4 +/- 62.5 ng/dl) (basal: 30.8 +/- 21.8 ng/dl), and of 3 alpha-Diol to 32.2 +/- 12.5 ng/dl (basal: 12.5 +/- 13.9 ng/dl). Plasma concentrations of T, DHT and 3 alpha-Diol then returned to basal concentrations within 24 hours. Using mass-spectrometry we found a cumulative renal excretion of 13C-labelled T of 15.6 +/- 9.6 micrograms/24 h, equivalent to 0.08 +/- 0.05% of the infused amount (20 mg) of [13C]T. Whereas urinary excretion of [13C]DHT was below the level of detection by mass-spectrometry the cumulative excretion of [13C]3 alpha-Diol was 67.7 +/- 19.9 micrograms/24 hours which is equivalent to 0.3 +/- 0.1% of the infused dose of 13C-labelled testosterone. These data suggest that the determination of urinary 3 alpha-Diol by mass spectrometry during/after the infusion of stable-labelled testosterone represents an alternative to the use of radioactive label for turnover studies. PMID- 3347045 TI - Aromatization of testosterone and 19-nortestosterone by a single enzyme from equine testicular microsomes. Differences from human placental aromatase. AB - A single enzyme in the stallion testis was able to aromatize both testosterone and nortestosterone. This enzyme had a much lower affinity for nortestosterone than for testosterone. In contrast to human placental estrogen synthetase, this enzyme aromatized testosterone and 19-nortestosterone with similar efficiency. The differences observed (effects of monovalent cations, inhibition of androstenedione aromatization by testosterone and 19-nortestosterone and, above all, rate of norandrogen aromatization) suggest that the aromatase in the horse testis is not the same as that in the human placenta. PMID- 3347044 TI - Structure-activity relationships of steroid hormones on muscarinic receptor binding. AB - A total of fifty steroidal compounds were tested for their inhibition on the binding of muscarinic receptor antagonist, [3H]quinuclidinyl benzilate ([3H]( )QNB), to the hypothalamic membranes prepared from male rats. Among the compounds tested, the active structures (with IC50 values less than or equal to 100 microM in parentheses) are: progesterone (40), 5 beta-pregnane-3,20-dione (40), deoxy corticosterone (50), 5 beta-pregnane-17 alpha,21-diol-3,20-dione (30), 11-desoxy 17-hydroxycorticosterone (22), 17 alpha-hydroxyprogesterone (20), 5 beta-pregnan 17 alpha-ol-3,20-dione (24), 5 beta-androstane-3,17-dione (100), and 5 beta dihydrotestosterone (100). By examining all the compounds tested, the following structure-activity relationship became apparent: (a) The ring A-reduced steroidal structures with a 5 beta-conformation were more potent than those with a 5 alpha conformation; (b) 17 alpha-hydroxylation of the steroidal ring increased the steroid's inhibitory activity; (c) The C3 carbonyl group was essential for activity; (d) Reduction of the C3 carbonyl group or aromatization of the ring A abolished the steroid's inhibitory activity; (e) Oxidation of the C11 position of ring C resulted in a decrease or loss of inhibitory activity; and (f) Different modifications of the side chain of ring D by acetylation resulted in either an increase or a decrease in the inhibitory activity. The structure-activity relationship as revealed in this study might provide an insight for the synthesis of a steroidal molecule with a high affinity for the muscarinic receptor as well as for the search of a more potent and physiologically relevant steroidal metabolite possessing the ability to interact with the muscarinic receptor. PMID- 3347046 TI - Interaction of glucocorticoid receptor from rat liver with protamine and arginine. AB - The nontransformed glucocorticoid receptor (GR) from rat liver was found to bind to protamine-Sepharose and could be recovered by a salt gradient without a change in molecular configuration. The nontransformed GR also bound to arginine Sepharose, but the transformed GR did not bind to either resin. Ligand-free GR interacted with both resins and was eluted without loss of its steroid binding ability. The bindings of GR to protamine- and arginine-Sepharose were saturable. The apparent dissociation constants of GR on protamine-Sepharose varied from 0.34 nM (-molybdate) to 0.68 nM (+ 10 mM molybdate) and those on arginine-Sepharose were 1.99 nM (-molybdate) and 0.65 nM (+ 10mM molybdate), respectively. The maximum binding capacity was achieved by arginine-Sepharose in the absence of molybdate. Higher salt concentrations (0.5 M NaCl) were required to elute GR from protamine-Sepharose than from arginine-Sepharose (approx 0.03 M NaCl). However, the effectiveness of several salts for the elution of GR was consistent in both resins as follows; MgCl2 = CaCl2 = Na2WO4 greater than (NH4)2SO4 = Na2MoO4 greater than arginine-HCl greater than lysine-HCl greater than KCI = NaCl. These results suggest that GR interacts with arginine residues in protamine. Chromatography using these resins resulted in 7-10-fold purification of occupied and unoccupied nontransformed GRs. PMID- 3347047 TI - In vitro metabolism of the cardiotonic steroids gomphogenin and calactin. AB - The metabolism of gomphogenin and calactin was studied in vitro using respectively microsomes and the S9 fraction of homogenates from rat liver. These two substrates were previously shown to be in vitro and in vivo metabolites of gomphoside, a cardiotonic steroid belonging to a class of 5 alpha-cardenolide glycosides with doubly-linked hexosulose sugars. Structures of new metabolites were elucidated using 400 MHz 1H-NMR and chemical ionization mass spectrometry, while known compounds were identified by direct comparison. The major metabolite isolated from gomphogenin (2 alpha-hydroxyuzarigenin) metabolism was the oxidation product 2-oxo-uzarigenin which was further oxidized metabolically to 4 alpha-hydroxy-2-oxo-uzarigenin. Other metabolites were 2 alpha-hydroxyuzarigenone and its reduction product 3-epigomphogenin. Calactin was oxidized in vitro to 10 carboxyl-19-norgomphoside, the predominant metabolite, and underwent cleavage of the doubly-linked sugar to yield calotropagenin. PMID- 3347048 TI - HPLC separation of corticosterone metabolites and its use in following corticosterone metabolism and transport in the isolated rat hepatocyte. AB - Incubating isolated rat hepatocytes with tritium labelled and unlabelled corticosterone at 37 degrees C resulted in the rapid appearance of at least nine corticosterone metabolites. A quick, relatively easy, and quantitative high performance liquid chromatographic (HPLC) method was used to separate these metabolites and follow their rate of appearance both intra- and extracellularly. We found different intra- and extracellular amounts of each metabolite at a particular time and this suggested that some metabolites were more available for transport than others. PMID- 3347049 TI - The isolation and characterization of estrogen binding proteins in the pancreas of male and female hamsters. AB - Specific estradiol binding proteins (EBP) that have been described in the pancreatic tissues of a number of species are thought to be important in maintaining the structural and functional integrity of the pancreas. However, possible sex-related differences in the presence and characteristics of EBP have not been examined. In the present study, we have analyzed the pancreatic tissues of male and female Syrian golden hamsters for the presence of EBP and progesterone binding protein (PBP), and further characterized these sites. Our results indicate the presence of only one class of EBP with a high capacity (greater than 500 fmol/mg protein) and low affinity (Kd greater than 1.0 nM) in the pancreatic cytosol of female hamsters. On the other hand, there appeared to be two distinct classes of EBP in the male pancreas. One class of EBP in the male pancreas had a high binding affinity (Kd = less than 0.05 nM) and low capacity (less than 10 fmol/mg protein); we have arbitrarily called these Type I EBP. The second class of EBP in the male pancreas which resembled EBP in the female pancreas had a high capacity (greater than 100 fmol/mg protein) and a low binding affinity (Kd = greater than 1.0 nM); we have called these Type II EBP. The sucrose-density gradient profile of EBP for male and female hamster pancreas demonstrated the presence of both an 8S binding protein and a 4S binding protein in the male pancreas; the female pancreas had only a 4S binding protein. PBP were not detected in pancreas of either male or female hamsters. We conclude that significant sex-related differences are present in the EBP populations of the hamster pancreas. PMID- 3347050 TI - Transformation of the glucocorticoid receptor in the cell-free cytosol of the neural retina of the chick embryo: changes in the size and charge of the receptor complex during transformation suggest a multistage process. AB - The physicochemical properties of the glucocorticoid receptors (GR), and the molecular changes induced during their transformation in the cell-free cytosol of the neural retina of the chick embryo, were investigated. The surface charge of the various size forms of the GR complex was determined on gel filtration and/or glycerol density gradient-isolated GR, by electrofocusing under nondenaturing conditions. The nontransformed molybdate-stabilized GR in hypotonic buffer (containing PMSF) appears as a 350 kilodalton (kDa) complex (Rs = 8.6 nm, S = 9.5), with an apparent pI value (pI') of 4.4 +/- 0.1. The GRs in heat or salt activated cytosols appear as a 90 kDa hormone-receptor complex (Rs = 5.6 +/- 0.2, S = 3.9 +/- 0.1), which is resolved as a major peak with a pI' value of 6.2 +/- 0.1 and a minor peak with a pI' value of 5.4. The transformation of the 350 kDa oligomer to the 90 kDa monomer occurs in three stages. Two distinct dissociation steps were induced by 0.4 M KCl: (a) the dissociation of the 350 kDa complex to a 170 kDa complex (Rs = 7.8 +/- 0.2, S = 5.1 +/- 0.2), exhibiting a pI' value of 5.6 +/- 0.2, induced by salt and not inhibited by molybdate; and (b) the dissociation of the 170 kDa complex to the 102 kDa complex (Rs = 5.6 +/- 0.2, S = 4.4), also exhibiting a pI' value of 5.6 +/- 0.2, which is blocked by molybdate. The third step, the transition of the 102 kDa complex to the activated (nuclear like), 90 kDa form, is dependent on cytosolic factors. It is induced in the isotonic milieu by physiological temperatures, and in the cold by exposing the crude cytosol to 0.4 M KCl. The nature of this cytosolic processing step is unknown. It occurs in the presence of PMSF, which presumably inhibits proteolytic GR degradation in the cytosol of the neural retina. Activated GR complexes tend to aggregate. Molybdate inhibits activation-induced GR-aggregation. PMID- 3347051 TI - Origin of deoxycorticosterone and deoxycorticosterone sulfate in human pregnancy: absence of steroid 21-sulfatase activity in sulfatase-deficient placenta. AB - The activity of steroid 21-sulfatase, the enzyme that catalyzes the hydrolysis of deoxycorticosterone sulfate (DOC-SO4) is demonstrable in human placenta. Thus, it is possible that this placental enzyme, by way of the hydrolysis of either DOC SO4 or 21-hydroxypregnenolone mono- or di-sulfate of fetal origin, may be important in the biosynthesis of DOC, which is present in the plasma of pregnant women in high concentration. To investigate this issue further, we evaluated steroid 21-sulfatase activity in microsomal preparations of a sulfatase-deficient placenta. Immediately after delivery, at term, of a living male fetus with sulfatase deficiency, a microsome-enriched fraction of placental tissue was prepared; sulfatase activity was evaluated by use of three substrates, viz. dehydroisoandrosterone sulfate (DS), estrone sulfate (E1-SO4), and DOC-SO4, in various concentrations. Similar incubations were conducted with aliquots of a microsome-enriched fraction prepared from placental tissue of a normal fetus that was delivered, at term, within minutes of the time of delivery of the infant with sulfatase deficiency. In microsomal fractions from the normal placenta, each of the steroid sulfates was hydrolyzed. In the absence of microsomes, and in the presence of microsomal fractions from the sulfatase-deficient placenta, the hydrolysis of DOC-SO4 and DS was not detected. Moreover, in microsomes prepared from the sulfatase-deficient placenta, E1-SO4 was hydrolyzed at a rate that was only 10% of that in incubations with microsomal preparations of the normal placenta. We conclude that with sulfatase deficiency, the placenta is deficient not only in sulfatase activity for steroid-3-sulfates but for steroid 21 sulfates, e.g. DOC-SO4, as well. PMID- 3347053 TI - Activation of the estrogen receptor from N-nitrosomethylurea-induced rat mammary tumors. AB - The activation of the estrogen receptor (ER) from N-nitrosomethylurea (NMU) induced rat mammary tumors was studied in vitro. The activation of the receptor induced by heating of the cytosol containing occupied ER was measured by a 3-4 fold increase of receptor binding to nuclei in comparison with the nuclear binding of the nonactivated ER. The activation of the ER was further shown by alteration of the elution profile from DEAE-cellulose. A shift of the receptor peak from 234 mM (Peak II, nonactivated ER) to 70 mM (Peak I, activated ER) phosphate buffer could be obtained. The overall recoveries of activated ER following chromatography on DEAE-cellulose were significantly lower than the recoveries of the nonactivated ER, 71 and 85%, respectively. Binding of the activated ER to nuclei and chromatography of the supernatant which is not able to bind to nuclei on DEAE-cellulose resulted in a decrease of Peak I and in an increase of the overall recovery. These findings suggest that the nuclear bound ER consists of two parts. One is represented partially by Peak I of the elution profile and the other one by that part of the receptor which can not be eluted from the column under the conditions used. Furthermore, the dissociation of tritiated estradiol (E3H) from the nonactivated ER followed a two component exponential function whereas after activation a monophasic dissociation curve could be observed. The mean half times for the dissociation of E3H from the activated and nonactivated ER were 101 and 7.2 min, respectively. Finally, the nonactivated molybdate stabilized ER sedimented in 5-20% sucrose density gradients as two peaks, one at 9.5 S and the other at 4 S. After activation of the ER only the smaller 4 S peak was evident. Molybdate inhibited the activation of the ER measured by nuclear binding assays, sucrose density gradient analysis, dissociation kinetics or ion exchange chromatography but not completely in every case. PMID- 3347052 TI - RU486 inhibits induction of aromatase by dexamethasone via glucocorticoid receptor in cultured human skin fibroblasts. AB - Effects of RU486 on the induction of aromatase by dexamethasone via glucocorticoid receptor were determined using cultured human skin fibroblasts. Competition of [3H]dexamethasone binding to the cytosol receptor was 7 times stronger with RU486 than with dexamethasone. The order of the strength of competition was RU486 greater than dexamethasone greater than betamethasone greater than prednisolone greater than hydrocortisone. RU486 abolished a specific 8.6 S [3H]dexamethasone binding peak in the cytosol, determined using a sucrose density gradient analysis. Dexamethasone markedly induced aromatase and this event was strongly suppressed by RU486, in a dose-dependent manner, in the cultured skin fibroblasts. A linear correlation between the strength of competition and the induction of aromatase of various glucocorticoids was observed. RU486 non-competitively inhibited aromatase induction by dexamethasone determined from a double reciprocal plot of aromatase activity, with respect to [3H]androstenedione concentration in the presence of RU486. These results show that RU486 is a peripheral noncompetitive antiglucocorticoid on aromatase induction by glucocorticoid in human skin fibroblasts and that aromatase induction is a good marker for the biological function of glucocorticoid receptor in human skin fibroblasts. PMID- 3347055 TI - Estrogen- and antiestrogen-induced ornithine decarboxylase activity and uterine growth in the rat. AB - The estrogen antagonists tamoxifen and monohydroxytamoxifen are also classified as partial estrogen agonists. In infantile rats, estradiol induced a single peak of uterine ODC activity at 6h following injection regardless of the extent of induction by various estradiol doses. By contrast, the timing of the ODC activity peak induced by tamoxifen and monohydroxytamoxifen was highly dependent upon the dosing conditions and was delayed to 18 h at lower tamoxifen doses. In immature rats, tamoxifen and monohydroxytamoxifen induced two peaks of uterine ODC activity resembling those induced by estradiol. Both ODC activity peaks were delayed by 9 h, without decreases in peak heights, by a 50-fold tamoxifen dose reduction. In all experiments the initial appearance of antiestrogen- and estradiol-induced ODC activity corresponded to initial uterine wet weight gain regardless of dosing condition. Thus, when dose-related temporal shifts are taken into account, tamoxifen and monohydroxytamoxifen are complete agonists with respect to induction of uterine weight gain and ODC activity. PMID- 3347054 TI - The effect of progestin on rabbit endometrial aromatase activity. AB - The ability of rabbit endometrium to synthesize estrogen was investigated. Aromatase activity was measured by incubating the viable tissue fragments with [3H] testosterone at 37 degrees C and quantitated the [3H]estrogens at the end of 6 h incubation. The activity was not detectable in endometrium and myometrium of non-pregnant rabbits. In pregnant rabbit, the activity increased from 2 to 12 fmol/h/g of tissue in endometrium obtained from both gravid and nongravid uterine horns 4-8 days after mating. Aromatase activity in endometrium at implanted sites on the 8th day after mating reached up to 550 fmol/h/g of tissue. Hormonal regulation of the aromatase activity was studied directly in cultured rabbit endometrial stromal cells. Both progesterone and medroxyprogesterone acetate stimulated the activity with 2- to 25-fold increase over the control values (0.2 1 fmol/h/mg protein). The stimulation of aromatase activity by progestin was found to be both time- and dose-dependent. Estrogen, Bu2cAMP, forskolin, HCG or relaxin had no effect on the activity. Aromatase activity in glandular epithelial cells was neither detectable nor affected by progestin. These results indicate that aromatase activity in rabbit endometrium is concentrated in stromal cells and progestin stimulates the activity. However, estrogen, forskolin and relaxin which enhanced the stimulation of the activity by progestin in human endometrium had no effect on aromatase in rabbit endometrium. The increase of aromatase activity observed after the onset of conception may be physiologically important to increase the local estrogen content for decidualization of the endometrium. PMID- 3347056 TI - Inhibition of human placental aromatase in a perfusion model. Comparison with kinetic, cell-free experiments. AB - In vitro perfusion of human placenta was evaluated for characterization of aromatase inhibitors. The results were compared with those in kinetic experiments in cell-free system. Inhibition constants (Ki) were determined by measuring the release of tritiated water during coincubation of human placenta microsomes with varying amounts of [1 beta,2 beta 3H]androstenedione and inhibitor in the presence of NADPH-generating system. Irreversible inactivation constants (Kinact) were determined in a similar manner following preincubation of the microsomes with different amounts of inhibitor for varying times. Lineweaver-Burk plots indicated a competitive type of inhibition with Ki values of 37 nM for 4-hydroxy androstenedione, 3,700 nM for testolactone, 15 nM for 1-methyl-androsta-1,4-diene 3,17-dione, and 7.5 nM for 19-azido-androstenedione. Additionally, irreversible enzyme inactivation by all four substances could be demonstrated with Kinact values of 3.64 x 10(-3), 0.57 x 10(-3), 0.34 x 10(-3), and 0.69 x 10(-3)sec-1, respectively. Perfusion of a single cotyledon of human term placenta was performed by infusing medium through catheters placed in a fetal artery and in the maternal intervillous space. Perfused medium was collected from a cannulated fetal vein and from the maternal basal plate. The medium was supplemented with [3H]androstenedione (4.2 nM) and inhibitor. The perfusates were analyzed for their [3H]estrone and estradiol content following phenolic partition and Sephadex LH 20 chromatography. The main results were, (1) the recovery of labelled steroids increased rapidly after perfusion started and reached a plateau within 60 min, when 55 and 30% (mean values) of the infused radioactivity were recovered in the fetal and maternal perfusates, respectively, (2) similar amounts of estrone and estradiol were found in both effluates, whereas androgens (mainly androstenedione and lower amounts of 5 alpha-androstane-3,17-dione) were found nearly exclusively in the fetal perfusate, (3) formation of estrogens (estrone + estradiol) reached a plateau within 20 min of perfusion. (4) The percentage of estrogens formed was not changed by increasing androstenedione concentration in the perfusion medium unless this concentration exceeded 3.5 microM indicating limited capacity of aromatase. (5) The four aromatase inhibitors reduced estrogen formation by 50% at concentrations about 100-fold of their Ki determined in the cell-free system, (6) irreversible aromatase inhibition could not be demonstrated in the perfusion model. It was concluded that the human placenta perfusion model can be successfully used to evaluate aromatase inhibitors. PMID- 3347057 TI - Adenosine effects on hormone-stimulated steroidogenesis in isolated bovine adrenal zona fasciculata cells. AB - In isolated bovine adrenal zona fasciculata cells, the use of adenosine deaminase to remove endogenous adenosine had no effect on basal or angiotensin II stimulated steroidogenesis but enhanced ACTH1-24-stimulated steroidogenesis over the entire dose response range without appreciable change in potency of ACTH1-24. 8-Phenyl-theophylline, an adenosine antagonist, mimicked all of the actions of adenosine deaminase. High concentrations (greater than 1 microM) of N6 phenylisopropyl-adenosine (PIA) increased basal, angiotensin II and cyclic AMP stimulated steroidogenesis, whilst inhibiting the ACTH1-24-stimulated condition. PIA also increased the potency of angiotensin II approx 20-fold. These observations are consistent with the possibility that adenosine exerts effects on two different signalling systems within zona fasciculata cells. PMID- 3347058 TI - Affinity chromatography using competitive elution separates polyclonal glucocorticoid antisera into fractions of varying cross-reactivity. AB - Affinity chromatography of glucocorticoid antisera using cross-reacting steroid Sepharose columns and competitive elution with the immunising steroid has allowed the separation of polyclonal antibodies into fractions of varying cross reactivity. Elution was at neutral pH in the presence of 20% acetonitrile followed by dissociation of the eluted immunoglobulin-steroid complex, by dialysis. A polyclonal cortisol antibody with an initial 70% cross-reactivity to 11-deoxycortisol yielded a fraction with 10% cross reactivity and improved affinity. This fraction was suitable for determining plasma cortisol on patients undergoing the metyrapone test whereas another fraction of similar affinity but higher cross reactivity to 11-deoxycortisol, as well as the intact antiserum, grossly over-estimated plasma cortisol on these patients. This technique should permit the use of antibody fractions for immunoassay when the intact antiserum may be unsatisfactory due to lack of specificity. PMID- 3347059 TI - High-performance hydrophobic interaction chromatography of estrogen receptors and magnesium dependent protein kinase(s): detection of two molecular forms of estrogen receptors in the presence and absence of sodium molybdate. AB - The separation characteristics of estrogen receptors (ER) from human breast cancer were evaluated based on their hydrophobic properties. Results show that (1) two distinct hydrophobic isoforms of ER exist either in the presence of sodium molybdate (peaks MI and MII with retention times of 15-17 min and 24-26 min) or in its absence (peaks I and II with retention times of 25-27 min and 34 36 min respectively); (2) this is observed whether molybdate (MoO2-4) is added to prepared cytosol or to the buffer prior to homogenization; (3) isoform MII and I separated with similar retention times suggesting they are the same ER species; and (4) isoform MI (Rt = 15-17 min) is a distinct ER species from either MII/I (Rt = 25-28 min) or II (Rt = 34-36 min). The latter isoform represents a highly hydrophobic species seen only in the absence of MoO2-4. Finally, (5) MoO2-4 ions appear to interconvert the most hydrophobic species (II) into the least hydrophobic isoform (MI) with virtually no change in the quantity of isoform(s) MII/I. However, it cannot be ascertained if the II----MI interconversion proceeds via isoform MII/I. Isoform II may result from the interaction with the stationary phase via its DNA binding site since MoO2-4, which is suggested to directly interact with this site, selectively interacts with peak II. These results imply the usefulness of inclusion of receptor stabilizing reagents in the mobile phase for preserving receptor integrity and in elucidating the interrelationships of ER isoforms and associated macromolecules. PMID- 3347060 TI - Estradiol assay by microtitre plate enzyme immunoassay. AB - Development of a simple enzyme linked immunosorbent assay (ELISA) for estradiol in serum extracts is described. The assay involves use of a 96-well microtitre plate, designed for immunoassay, as the support for a purified, high-titre antiserum, raised against estradiol-6(O)-carboxymethyloxime linked to bovine serum albumin, and using horseradish peroxidase-labelled estradiol-6-(O) carboxymethyloxime as the labelled species, with 2,2'-azino-bis-(3 ethylbenzthiazoline sulfonic acid) diammonium salt (ABTS) as the chromogenic substrate. The assay characteristics rival those of radio- or chemiluminescence immunoassays for estradiol. PMID- 3347061 TI - Comparative structural analyses of corticosteroid binding globulin. AB - Some physicochemical characteristics of corticosteroid binding globulin (CBG) in several species have been determined. Molecular radii were determined from Ferguson plots and were used in conjunction with sedimentation coefficients determined by sucrose density gradient centrifugation to calculate the molecular weights of the CBG. These were found to range from 44,200 (dog) to 60,000 (turtle) for most species. The squirrel monkey was found to have a molecular weight twice that of other species (119,800). Purified CBG was prepared from human, rat, and guinea pig sera. The molecular weights of the purified material, as determined by gel electrophoresis in the presence of sodium dodecyl sulfate, were in excellent agreement with those determined by Ferguson analysis. Careful examination of the purified proteins by electrophoresis at pH 8.3 revealed that each consisted of two closely related electrophoretic variants. Tryptic peptides were prepared from the purified proteins and separated by reversed phase HPLC chromatography. The peptide patterns were identical for the three proteins with the exception of three hydrophilic peptides. Amino terminal sequence analysis of the rat and human proteins revealed no apparent homology, however. The immunologic relatedness of the three purified proteins was also examined, but no crossreactivity was observed. The results obtained suggest that while the molecular size and hydrophobicity of peptides have been conserved across species considerable surface differences must exist. PMID- 3347062 TI - Kinetic studies of inhibition of estradiol 2- and 16 alpha-hydroxylases in rat liver microsomes with various cytochrome P-450 inhibitors. AB - Kinetic studies of inhibition of estradiol 2- and 16 alpha-hydroxylase activities in male rat liver microsomes with cytochrome P-450 inhibitors, alpha naphthoflavone, DL-aminoglutethimide, SKF-525A and metyrapone, were extensively carried out. All of the inhibitors competitively blocked the two enzyme activities. The former three inhibitors preferentially inhibited the 16 alpha hydroxylase activity while the reverse result was obtained in the case of metyrapone, and SKF-525A was the most potent inhibitors for the two enzyme among the four inhibitors. The kinetic data, the apparent Ki's for the four inhibitors and Km's for the substrate estradiol in the assays, along with the inhibition results with carbon monooxide suggest that different forms of cytochrome P-450 may be involved in the two hydroxylations. Kinetic parameters of the two hydroxylase activities in female rat liver microsomes were then determined to be an apparent Km of 23.0 and 158 microM and Vmax of 99.0 and 5.65 pmol/min/mg protein for the 2-hydroxylation and the 16 alpha-hydroxylation, respectively. The kinetic data show that the 2-hydroxylation may be quantitatively an exclusive hydroxylative pathway in estrogen metabolism in female. PMID- 3347064 TI - A model of antiglucocorticoid action for designing a potent glucocorticoid antagonist. AB - We have previously shown that the biological efficacy of an antiglucocorticoid is directly related to its affinity for the glucocorticoid receptor in whole cells at 37 degrees C. We have also shown that RU 486-receptor complexes differ from other antiglucocorticoid-receptor complexes in so far as their affinity is as high at 37 degrees C in whole cells as at 0 degree C in a cell-free system, whereas a decrease by a factor of 5-10 is observed with the other antagonists. The aim of the present paper was to evaluate the contributions of temperature and cellular integrity (or the biological events linked to temperature and cellular integrity) to the affinity of a steroid for its receptor for the purpose of determining the parameters favorable to high affinity, which is the prerequisite of a potent antagonist. We provide evidence showing that: (1) an increase in temperature has an unfavorable effect on the affinity of a glucocorticoid for its receptor (4-6-fold decrease between 0 and 37 degrees C), (2) RU 486, like an agonist, forms a complex with the cytosolic glucocorticoid receptor, which satisfies the criteria for an "activated" complex under "in vitro activating treatment", (3) these biological post-binding events (either agonistic or otherwise nature), which change the nature of the complexes, contribute to compensating for the negative effect of rising temperatures on their apparent dissociation constant. We conclude that potent antiglucocorticoids must have a chemical structure allowing them to induce biological post-binding events, such as receptor activation, but in an abortive form which thus effectively "traps" the receptor in a non-functional state. PMID- 3347063 TI - Hepatic microsomal metabolism of androst-4-ene-3,17-dione: relative importance of ring hydroxylation and aromatization in control and induced rat liver. AB - The purpose of these studies was to determine whether oestrogen production is a quantitatively important pathway in the hepatic microsomal metabolism of androst 4-ene-3,17-dione. The effects of the enzyme inducing agents phenobarbitone and beta-naphthoflavone on microsomal cytochrome P-450-mediated androst-4-ene-3,17 dione hydroxylation and aromatization was investigated in the rat in vitro. In microsomal fractions from untreated rats the ratio of hydroxylated products to aromatized (oestrogenic) metabolites was 33:1. Phenobarbitone pretreatment of rats increased total hydroxylation by about 20% but did not change the ratio of hydroxylated to aromatized products (27:1). In contrast, beta-naphthoflavone induction decreased total hydroxylation to about 35% of control but did not affect total aromatization. Thus the ratio of hydroxylation to aromatization was significantly lower than in control microsomes (17:1). The principal aromatized products were oestriol and 2-hydroxyoestradiol-17 beta, with oestradiol-17 beta and its 4-hydroxy metabolite as minor products; no oestrone was observed. In further studies of the microsomal metabolism of oestrone, the major product was oestradiol-17 beta whereas hydroxylated metabolites were only minor products. Oestradiol-17 beta, in contrast, was hydroxylated to a considerable extent. These findings suggest that oestrone is a better substrate for the microsomal 17 beta oxidoreductase than it is for cytochrome P-450. It therefore appears likely that any oestrone formed from the aromatization of androst-4-ene-3,17-dione would be readily converted to oestradiol-17 beta which, in turn, is subject to cytochrome P-450-mediated hydroxylation. Although the liver is a site of C19-steroid aromatization, it appears unlikely that this organ could contribute significantly to serum oestrogen levels since microsomal hydroxylases are readily able to convert aromatized products to biologically inactive metabolites. PMID- 3347065 TI - Corticotropin-induced changes in enzymatic activities of the post-pregnenolone steroidogenic pathway in rabbit adrenocortical cells. AB - In an attempt to delineate the effect of corticotropin (ACTH) on post pregnenolone steroidogenesis, the activity of enzymatic systems operative in conversion of pregnenolone into glucocorticoids and androgens was studied in adrenocortical cells from control rabbits and from animals treated with ACTH for 12 days (ACTH 1-24, 200 micrograms s.c. daily). The cells from ACTH-treated rabbits exhibited an increased overall steroidogenic capacity and produced much more cortisol (P less than 0.0005) as well as other 17-hydroxylated steroids as a result of increased activity of 17 alpha-hydroxylase; corticosterone generation was concomitantly reduced. The increased conversion of pregnenolone or progesterone into androgens, as a result of previous treatment with ACTH, provides additional evidence for an effect of ACTH on 17 alpha-hydroxylase activity. A stimulatory effect of ACTH on 11 beta-hydroxylase was also evidenced by these cells, since conversion of 11-deoxycortisol into cortisol was enhanced (P less than 0.005). The increased production of androgens from 17-hydroxylated precursors by cells from ACTH-treated rabbits suggests that ACTH also exerts a prolonged stimulatory effect on 17,20-lyase. The activity of 3 beta hydroxysteroid dehydrogenase-isomerase was apparently not influenced by chronic treatment with ACTH, judged from unchanged conversion of dehydroepiandrosterone into androstenedione. The activity of 11 beta-dehydrogenase was likewise unchanged in these conditions. PMID- 3347066 TI - Corticosteroids stimulate an increase in phospholipase A2 inhibitor in human serum. AB - A corticosteroid induced increase in a circulating inhibitor of serum phospholipase A2 activity is described. Inhibitor activity was found to be normally present in serum in agreement with the findings of other workers, and this activity was significantly increased by either acute or chronic administration of corticosteroids. The possible relation of this inhibitor to the known inhibitory effects of lipocortin and sphingomyelin on phospholipase A2 activity is briefly discussed. PMID- 3347067 TI - Rearrest following residential treatment for repeat offender drunken drivers. AB - Multiple offenders are at high risk for continued drunken driving. Massachusetts, therefore, mandated that individuals convicted of a second drunken driving offense either be committed for a minimum of 7 days in a house of correction or enter a 14-day residential alcoholism treatment program for second offenders. A 2 year follow-up study of arrest rates assessed the impact of the two sentencing options on subsequent arrests for driving under the influence of liquor (DUIL). The incarcerated sample (N = 190) was slightly younger, had more prior DUIL charges and exhibited greater criminality than those who entered treatment (N = 199). Offenders admitted to the 14-day program were significantly less likely to be rearrested for drunken driving (10 vs 20%). A summary odds ratio suggested that when adjusted for differences in prior arrests, the risk of rearrest was 1.9 times greater among incarcerated offenders. Although a 2-year follow-up is insufficient to assess the complete impact of the 14-day program, the two-fold difference in the risk of rearrest suggests that mandated short-term residential treatment may provide an effective intervention among repeat offender drunken drivers. PMID- 3347068 TI - Alcohol consumption indices: format comparisons. AB - Three methods for wording quantity-frequency indices of alcohol consumption were compared over three time periods. Wording changes were associated with significant differences in mean scores, suggesting that comparative research results dependent on means might be reflecting measurement error rather than reality. The results of factor analysis and correlation analysis, however, supported the reliability and interchangeability of the three forms for purposes of scale construction and establishment of relationships. PMID- 3347069 TI - The relationship between relapse and involvement in alcoholics anonymous. AB - Recovering alcoholic members (N = 59) of Alcoholics Anonymous (A.A.) were asked to complete a questionnaire to assess the occurrence of relapse and its correlation to their level of involvement in the A.A. program. The questionnaire was distributed to five different A.A. groups. Subjects were asked to rate themselves, using a Likert scale, on their level of involvement in the A.A. program and were also asked to state if they had relapsed during the course of their involvement with A.A. and if so, to indicate their most recent relapse. Depending on their answers to the relapse question, subjects were placed in either a relapse or a no relapse group. The level of involvement in A.A. was found to be related to whether relapse occurred. Those in the relapse group rated themselves lower in every area of involvement listed on the questionnaire than those in the no relapse group. The most significant area of involvement, where the greatest differences between subjects in each group were found, was in reaching out to other members of A.A. for help and in the use of a sponsor. PMID- 3347070 TI - Predriving riders and drinking drivers. AB - A social learning model was used to investigate why young adolescents, 15 years of age and under, ride with drinking drivers. A total of 384 adolescents completed a self-report survey instrument. Zero-ordered correlations and regression procedures indicated that adolescents in this age group have a high frequency rate of riding with drinking drivers, and that social learning variables are important in explaining the behavior. Four of the five social learning subsets were accepted as significant in understanding the social dynamics of the problem. Prevention efforts that focus on predriving youth and account for social learning variables hold promise for the development of prevention strategies. PMID- 3347073 TI - Exploring Filipino American drinking behavior. AB - The purpose of this article was to explore characteristics distinguishing levels of drinking by Filipino Americans. A sample of 298 adult Filipinos was interviewed using a schedule based on a national study of drinking behavior and attitudes. Approximately 50% of the female sample were abstainers while 80% of the men were drinkers. Heavy drinking was almost exclusively a male activity. Thus, two models of Filipino drinking were examined. Logistic regression was used to identify social factors distinguishing female drinkers from abstainers. A second model clarified the influence of similar characteristics on male Filipinos who drank limited amounts of alcohol and those who drank heavily. The only variable significant in both models was regular participation in religious service. PMID- 3347072 TI - Male Chinese drinking behavior in Los Angeles. AB - The purpose of this research was to identify the characteristics that distinguish male Chinese drinkers from abstainers and to clarify differences between Chinese men who drink limited amounts of alcohol and those who drink more heavily. A random sample of 218 adult Chinese men was interviewed using a schedule based on a national study of drinking behavior. The stereotype of Chinese as limited drinkers was partially supported by the data. Approximately 22% of the sample were abstainers whereas only 14% were heavy drinkers. Light drinkers were the modal category. A logistic regression model was used to evaluate the relative importance of the significant characteristics of drinkers and abstainers. Parents' drinking behavior influenced respondent's drinking behavior, and drinkers tended to like to go to parties. Chinese men with higher education were more apt to be drinkers. A second logistic regression model was used to identify the predictive variables related to the level of drinking. Chinese men who go to bars and who have friends who drink were the most likely to be heavy drinkers. PMID- 3347071 TI - Antihistamine blockade of alcohol-induced flushing in orientals. AB - The so-called Oriental flushing reaction associated with ingestion of small amounts of alcohol was antagonized by combined antihistamine administration. In stage one of the study, the flushing reaction to low doses of alcohol was produced in Orientals. Most subjects experienced a cutaneous flush, an increase in skin temperature, a decrease in blood pressure, an increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness and nausea. Before the administration of alcohol, one-half of the subjects were given 50 mg of diphenhydramine (H1 receptor antagonist) and 300 mg of cimetidine (H2 receptor antagonist). The second half received placebo tablets. The clearest difference between the antihistamine group and placebo group was in the skin flushing reaction. The antihistamine group showed a significant reduction in the skin flush. The antihistamine also neutralized the systolic hypotension induced by the administration of alcohol. The possible importance of histamine in the expression of sensitivity to alcohol is considered. The relevance to genetic susceptibility for development of alcoholism is discussed. PMID- 3347074 TI - Relationship between self-control and alcohol consumption patterns and problems of college students. AB - The relationship between self-control strategies, alcohol-related problems and the quantity and frequency of alcohol use was examined. Analyses of data from 410 university students who completed the Student Alcohol Questionnaire and the Self Control Questionnaire indicated that both internal and external self-control strategies were significantly correlated with alcohol-related problems and alcohol consumption variables. Self-control strategies were also found to be applied differentially across drinking patterns and problem status. It was concluded that college students naturally attempt to control their alcohol consumption or the unwanted consequences related to drinking. Further research is needed to detail the self-change attempts of college-aged drinkers. PMID- 3347075 TI - Comprehensive evaluation of a model alcohol education curriculum. AB - A comprehensive evaluation was conducted of a representative alcohol education program designed to enhance knowledge and self-esteem, instill appropriate attitudes and teach the decision-making skills necessary for youth to make responsible decisions about the use of alcohol. The curriculum was implemented approximately as intended. The immediate, cumulative and longer-term effects of curriculum exposure on the variables thought to mediate alcohol use were modest or unsystematic. There was no consistent evidence of carryover effects from curriculum exposure on subsequent use of alcohol, cigarettes or other drugs. The curriculum was ineffective in attaining its goals. PMID- 3347076 TI - The problematic prospects for prevention in the classroom: should alcohol education programs be expected to reduce drinking by youth? AB - Junior and senior high-school students completed a questionnaire, either once or twice (in successive years), providing measures of variables in three principal sets: (1) curricular variables, those typically addressed in contemporary alcohol education programs (knowledge about alcohol, attitudes toward alcohol, decision making skills and self-esteem); (2) drinking behavior; and (3) noncurricular variables (demographic and social-psychological traits that typically characterize students before they are exposed to alcohol education programs). Bivariate analyses suggested that the curricular variables are related to drinking behavior, whereas multivariate analyses indicated that these same variables contribute little to the explanation of adolescent drinking when adjusted for the noncurricular variables, most of which are logically and/or chronologically prior to curriculum exposure. It is concluded that contemporary alcohol education programs do address variables that, when considered alone, appear to be related to drinking. However, these same variables make such a small independent contribution to drinking behavior that it is unlikely even a highly successful classroom intervention directed at these variables would do much to prevent alcohol use or abuse by youth. PMID- 3347077 TI - Nurse-identified problems in the management of alcoholic patients. AB - The purpose of this exploratory study was (1) to identify and rank the patient problems of hospitalized alcoholics that medical-surgical nurses view as difficult to manage, (2) to identify the factors that contribute to the difficulty in care, (3) to identify interventions used by nurses in an attempt to resolve patient problems and (4) to describe relationships between nurses and the identified patient problems. Subjects (N = 83) completed and returned an open ended questionnaire by listing the physiological and psychosocial patient problems, factors and interventions. Selected demographic and biographic data were also collected. A nursing diagnosis classification described by others served as a basis and was adapted for the nursing diagnosis categories. Nominal data were analyzed using frequency distributions and percentages. The most difficult physiological problems in caring for alcoholic persons were categorized from subjects' responses using the nursing diagnoses of "potential for injury," "alterations in nutrition-elimination" and "fluid volume deficit." The nursing diagnosis categories of "ineffective individual coping," "ineffective family coping" and "noncompliance" comprised the most difficult psychosocial patient problems. A majority of subjects reported having limited classroom and clinical experience with alcoholism; 80% expressed a need for additional inservice education. It is recommended that nursing educational programs include didatic and clinical content about alcoholism, focusing on problem areas identified and on family dynamics, communication, coping strategies and time-management strategies. PMID- 3347078 TI - Arrests of women for driving under the influence. AB - Police records of arrests of women in Wichita, Kansas for driving under the influence (DUI) of alcohol for a 5-year period (1980-1984) were studied. The proportion of arrests of women increased from 10.6 to 14.5% of total arrested. Women in their 20s comprised the largest age group; single women were greatly overrepresented. More than one-half of the arrested women were employed outside the home; a substantial proportion (30.8%) were unemployed at the time of arrest. The average blood alcohol level of those tested was 183 mg/dl. Characteristics of arrestees are discussed in terms of changes in the social roles and expectations of women. Although time of arrest was similar to that of men (i.e., night), arrests of women were more evenly spread across the days of the week. Within the 5-year period, the rate of recidivism for DUI was 7.43%. The implications of arrest and recidivism patterns are discussed. A change in legal and arrest procedures was found to have the same effect on arrests of women as it had on those of men, suggesting that the changes did not produce differential treatment by police. PMID- 3347079 TI - Differences in the self-depictions of female alcoholics and psychiatric outpatients: towards a depiction of the modal female alcoholic. AB - Forty-one Minnesota Multiphasic Personality Inventory (MMPI) items that differentiated modal female alcoholics from modal nonsubstance-abusing psychiatric outpatients at the p less than .0001 level of significance were located. A principal factor analysis of the 41 X 41 item-intercorrelation matrix yielded three factors which were labeled (1) Deviant Thrill-Seeking, (2) Remorseful Intrapunitiveness and (3) Blackouts. Nonmodal alcoholics, who comprised approximately 20% of the present sample, were found to be indistinguishable from modal psychiatric outpatients except for their excessive consumption of alcohol. PMID- 3347080 TI - Effects of alcohol on power in social interaction between man and woman. AB - From the McClelland et al. theory it was hypothesized that the distribution of power defined in terms of both outcome and process would be affected by alcohol in a man-woman dyad interaction situation by increasing power of the intoxicated partner. Man-woman couples (N = 30) were randomly assigned to an alcohol, a placebo or a control group. The men in the alcohol group were served a beverage containing 0.8 ml of absolute alcohol per kg of body weight. In the placebo group, the men were served a drink of orange juice and vodka essence, and the men in the control group received only orange juice. The women in all groups were served only orange juice. The same information about the kind of drinks to be served was given to both the men and the women in their respective groups. Each couple was tested individually and the experimental task consisted of 20 equal trials. The man and the woman were asked to give an individual estimation of the length of a line projected on a screen. They were then instructed to discuss their individual answers and to come to a mutual agreement on the length of the line. Outcome power was defined as the influence each one had on the actual decision and process power as each one's influence on the interaction process. Results clearly show that sober women increase their outcome power and responsibility aspects of process power over the intoxicated men, while the intoxicated men retain some of their process power as estimated in quantitative terms. The hypothesis was not supported and alternative explanations were discussed. PMID- 3347081 TI - Definition of onset in the development of onset-based alcoholism typologies. AB - Age of onset of alcoholism is gaining prominence as an explanatory construct in the development of models of alcoholism. Recently, at least one investigator has cited its potential as a simple means for deriving a typological classification scheme that could have great impact, both in terms of future research and in devising treatment strategies. Various investigators, however, operationalize alcoholism onset in different ways. By comparing five definitions of the concept, we show that the proportion of individuals classified as early or late onset can vary dramatically, depending on the interpretation given to phrases such as "subjective problems." Gender differences in early-late proportions are demonstrated, and the statistical relationship of the five items used as onset indicators is described. We suggest that collecting multiple convergent definitions of onset constitutes a structured recall aid that may ameliorate some of the problems to which self-report data are subject, while additionally providing the data necessary to create an aggregate measure that will increase reliability in comparison with the items individually. Finally, we encourage description of alcoholism onset as a developmental process rather than a single event, and urge investigators to increased precision in the operationalization of this construct as research in this area progresses. PMID- 3347082 TI - A structured diagnostic interview for identification of primary alcoholism: a preliminary evaluation. AB - Forty alcoholic inpatient men were used to evaluate the test-retest reliability and the validity of a new structured diagnostic interview. The Alcohol Research Center (ARC) Intake Interview was constructed from the Schedule of Affective Disorders and Schizophrenia (SADS) parts I and II and from the Diagnostic Interview Schedule family history section by extracting information on diagnoses most likely to be seen in alcoholic patients and by expanding the data set with questions relevant to alcohol and drug use. The test-retest reliability for patients' primary and secondary diagnoses included a kappa of 1.00 for the comparison of interviewers A and B (100% agreement) and of .76 for interviewers A and C. The validity of ARC Intake Interview patient diagnoses as compared to the SADS demonstrated an overall agreement between 91 and 100%. Reliabilities for labeling of families as positive or negative for specific illness in any first degree relatives revealed a kappa of 1.00; validities on family diagnoses ranged from 77 to 100%, with the ARC Intake Interview identifying more illness in families than the SADS. Although further evaluation of the ARC Intake Interview is needed, this instrument is recommended to investigators attempting to evaluate the clinical course and treatment needs among alcoholics, especially those patients presenting with multiple diagnoses. PMID- 3347083 TI - Learn to lobby. PMID- 3347084 TI - Health, welfare and government affairs. The legislative process made easy. PMID- 3347085 TI - Conditional cross-interval correlation analyses with applications to simultaneously recorded cerebellar Purkinje neurons. AB - Two conditional cross-correlation techniques are described for the analysis of two simultaneously recorded neuronal spike trains. The conditional interspike interval histogram describes the distribution of interspike intervals of a neuron conditioned by a preceding spike in another neuron. The conditional cross interval histogram describes the distribution of cross-intervals of two neurons conditioned by a preceding spike in one of the neurons. These techniques could be used to reveal the temporal coupling in the discharge of two neurons recorded simultaneously. The techniques augment the description of the correlation obtained with conventional cross-correlation measures. When applied to the simple spike discharge of simultaneously recorded cerebellar Purkinje neurons, the methods reveal temporal interactions between neurons that are not readily apparent from conventional cross-correlograms. The patterns observed suggest a tightly coupled, temporal surround-inhibition among nearby Purkinje neurons. PMID- 3347087 TI - A vector stimulator for neurophysiological studies of periodontal mechanosensitive units. AB - This paper describes a newly designed vector stimulator which can independently stimulate both sides of an animal's canine or incisor teeth to analyse the functional properties of periodontal mechanosensitive (PM) units. The stimulator was designed so as to control and stimulus direction (0 degree-360 degrees) and intensity (0-0.98 N) within the horizontal plane (vector), the rate of application (0.049-490 N/s), and the duration (0-10 s). The stimulator is composed of electromagnetic drivers, a trapezoid-wave generator, and a stimulus monitor. The former is adopted from conventional pen drivers, and the latter two are composed of operational amplifier circuits. The vector stimulator was utilized to apply a stimulus force to the canine teeth of a cat, and the responses of the PM units were recorded in the somatosensory cerebral cortex. PMID- 3347086 TI - An inexpensive, microcomputer-based system for recording movements in real time. AB - An inexpensive, microcomputer-based system was developed for recording movements in real time. The positions of 5 serially illuminated, infrared emitting diodes fixed on the object of interest were tracked by a remote, position-sensing photodiode. Positional information from the photodetector was digitized by an LSI 11/23+ microcomputer (sampling rate = 50/s/channel) and stored for subsequent analysis. Any microcomputer equipped to perform analog-digital conversion is compatible for use with this system. The small size of the components that are mounted on the animal allows movement to occur virtually unimpeded and makes this recording system especially suited for small animal observation. PMID- 3347088 TI - Preservation of the ependyma of the mouse spinal cord by various vascular perfusion procedures. AB - Seventy-two mice were used to find out which of 13 vascular perfusion procedures gave best structural preservation of the spinal cord ependyma and central canal lumen. Best results were obtained by 3% glutaraldehyde in Tyrodes solution with 50% of normal NaCl amount, 0.06 M sucrose and 2% dextran T-40 (556 mOsmol, pH 7.2, 0-4 degrees C). This was perfused by a peristaltic pump at 40 ml/min for 10 min through a cannula inserted in the ascending aorta. No advantage was seen by heparin pretreatment or adding a prefixation rinse. With good tissue preservation the central canal was found to be round to oval in cross-sectional profile and almost free of intraluminal material. PMID- 3347089 TI - Extracellular application of cobalt: a fast and simple method for delineating invertebrate neurosecretory pathways. AB - The extracellular cobalt backfilling technique was shown to be an excellent method to obtain cobalt backfills of invertebrate neurosecretory cells (NSCs). Aqueous cobalt was placed in an extracellular suction electrode into which a portion of a neurohaemal (NH) region containing the axons and/or terminals of NSCs was drawn. Spontaneously discharging extracellular action potentials were recorded as the cobalt was applied to the NH region, and the greater the electrical activity, the more extensive the cobalt backfilling. The greatest success occurred with 0.5 M cobalt chloride dissolved in physiological saline. No backfills were obtained in the absence of electrical activity. This technique was shown to backfill NSCs terminating in NH regions of the insect, Rhodnius prolixus, the isopod crustacean, Oniscus asellus, and the freshwater pulmonate snail, Helisoma. Combined with a light insensitive silver intensification method, this paper describes a relatively fast and simple method for delineating invertebrate neurosecretory pathways. PMID- 3347090 TI - A flow rate monitor for a variety of physiological preparations, including in vitro brain slices. AB - A flow rate monitor system for constant perfusion of media for maintaining physiological preparations, particularly in vitro brain slices, is described. The system consists of 3 components: the counter with a drip rate meter and alarm; a drop sensor; and a remote DC power supply. It provides accurate and immediate readout of flow rate in drops per minute and it provides an audio warning if the drip rate falls below a level set by the investigator. PMID- 3347091 TI - A procedure for culturing rat neocortex explants in a serum-free nutrient medium. AB - A procedure is described for long-term culturing of rat neocortex explants in a serum-free growth medium. Slices spanning the entire cortical depth from pial to ventricular side are prepared from 6-day-old rat pups. After preincubation in Hanks' balanced salt solution with extra glucose, the explants are placed on polyamide gauze carriers in plastic culture dishes containing serum-free medium. The dishes are continuously rocked during the culture period. After 3 weeks in vitro the explants consist of a three-dimensional network of neural tissue with a mean thickness above the gauze of ca. 100 micron which corresponds with about 8 cell layers. Central necrosis is either fully absent (in one-third of the explants) or restricted to a minimal strip or patch located close to the gauze. From pial to ventricular side, 5 layers can be distinguished which, with respect to cell size and cell density, reflect a histiotypic architecture. The dense neuropil shows abundant axo-dendritic synapses (both on shafts and spines), myelinated fibers, and spontaneous bioelectric activity. PMID- 3347092 TI - Translocation (6;9) may be associated with a specific TdT-positive immunological phenotype in ANLL. AB - Two patients with acute nonlymphocytic leukemia (ANLL) (FAB-M4) and t(6;9)(p23;q34) are described. Immunological marker analysis revealed a phenotype of HLA-DR+/partly terminal deoxynucleotidyl transferase (TdT)+/CD13+ in both cases and CD33 positivity in one. The expression of CD13 and CD33 by TdT-positive cells was demonstrated by double immunofluorescence staining. Although it has been postulated that TdT plays a role in gene rearrangement, Southern blot analysis performed in one leukemia revealed that both the T cell receptor beta chain genes and the immunoglobulin heavy chain genes were in germ line configuration. Since we could not detect CD13+/TdT+ cells and CD33+/TdT+ cells in control bone marrow samples, double marker analysis was used to detect low numbers of residual leukemic cells during follow-up of one patient. A gradually increasing percentage of CD33+/TdT+ cells was detected in the bone marrow in a period of 6 months before hematological relapse. Although the t(6;9) may not be correlated to a specific French-American-British subtype, it may be associated with TdT-positive ANLL. Since TdT-positive ANLL seems to have a poor outcome, detection of TdT expression in ANLL patients is particularly important for diagnostic purposes. In addition, our results indicate that double immunological marker analysis for a myeloid marker and TdT allows detection of residual disease during follow-up. PMID- 3347093 TI - Low dose Ara-C for patients with myelodysplastic syndromes. AB - Forty patients with high risk myelodysplastic syndromes--refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or chronic myelomonocytic leukemia--were treated with subcutaneous low dose cytosine arabinoside, 10 mg/m2 twice daily for up to 42 days. In 38 evaluable patients there were nine (24%) complete and four (11%) partial responses. Response was associated with symptomatic improvement and resolution of the need for red cell and platelet transfusions. The median duration of complete response was 9.8 months (range, 2.4-17.9); these patients had a median survival of 15.7 months (range, 6.0-22.7). Toxicities were predominantly those associated with pancytopenia, i.e., infection and hemorrhage. PMID- 3347094 TI - Multiple agent chemotherapy (POACH) in previously treated and untreated patients with chronic lymphocytic leukemia. AB - A multiple agent chemotherapy protocol utilizing cyclophosphamide, adriamycin, cytosine-arabinoside, vincristine, and prednisone (POACH) was administered to 65 patients with chronic lymphocytic leukemia. Nineteen (56%) of the 34 previously untreated patients responded, with (21%) of the patients obtaining a complete remission. The response rate for the 31 previously treated patients was significantly lower, with 2 complete remissions and 6 partial remissions. The median survival of the untreated patients was 58 months, compared with 15 months for the previously treated group (p less than 0.01). In both groups, patients who achieved a complete or partial remission had a significantly longer survival than did patients who did not respond. The response rates for all sites of involvement were similar. Sixteen (47%) of 34 previously untreated patients and 9 of 31 (29%) previously treated patients returned to Rai stage 0. The survival of patients who returned to stage 0 was significantly superior to that of others in both groups. The overall mortality during the study was significantly higher for previously treated patients. Pretreatment Rai stage was strongly predictive of death on study. Rai and Binet stages were not strongly predictive of response or length of survival in untreated patients but stages were predictive for survival and in treated patients. The regimen was well tolerated, with infectious complications being the major morbidity. Patients who responded to POACH had a significantly longer survival than did those who did not, and further attempts to improve the complete and partial remission rates in chronic lymphocytic leukemia will be undertaken. PMID- 3347095 TI - Demonstration of neural cell adhesion molecules on stromal cells that support lymphopoiesis. PMID- 3347096 TI - Effect of age on some properties of mice erythrocytes. AB - The hematological parameters of young (2-month-old) and old (2-year-old) mice were compared. No differences could be detected with the exception of an increased percentage of reticulocytes in the old animals suggesting that anemia in senescent mice does not occur. Red blood cell mean half-life in old mice was 8 +/- 0.8 days compared to 12 +/- 1 days in young mice. This reduced survival of red blood cell is not due to a different rate of cell phagocytosis in the reticulohistiocytic system of young and old animals since erythrocytes from young mice have the same mean half-life when injected both in young and old animals and vice versa. Thus, the old mice have a reduced red cell life-span but the same hematocrit of the young, suggesting that old animals possess a chronologically younger population of erythrocytes than do young animals. This has been confirmed by measuring the specific activities of some red blood cell age-dependent enzymes (hexokinase, glucose-6-phosphate dehydrogenase, pyruvate kinase) that were found to be higher in the older animals, and by the separation of erythrocytes into different density (age) groups by Percoll/albumin density gradient centrifugation. However, the erythrocytes osmotic fragility, and the cellular contents of adenine and pyridine nucleotides, as well as the content of 2,3 diphosphoglycerate and reduced glutathione, show that circulating erythrocytes in old animals constitute an heterogeneous cell population whose properties cannot be explained on the basis of a chronologically younger erythrocyte population. Furthermore, evaluation of cell components in hemopoietic tissues have shown an increased porportion of erythroid precursor cells in old animals confirming that old mice compensate for reduced red cell survival with an increased erythropoiesis. PMID- 3347097 TI - Aging and aortic impedance in beagle dogs. AB - Previous studies of the effect of aging on aortic impedance have proved inconclusive. Studies in man could be affected by clinically inapparent atherosclerotic effects which cannot be separated from aging effects. Therefore, to more directly examine the role of aging, hemodynamic studies were carried out in awake, resting young and senescent non-atherosclerotic beagles before and after the administration of various vasoactive agents. On separate days graded infusions of a rapid acting beta-adrenergic agonist and antagonist (isoproterenol and propranolol), and alpha-adrenergic agonist and antagonist (phenylephrine and phenoxybenzamine), combined alpha- and beta-adrenergic antagonists (propranolol plus phenoxybenzamine), and a non-specific vasodilator (nitroprusside) were administered. Aortic impedance was calculated from high-fidelity pressure and flow signals using standard Fourier analysis methods. Under baseline conditions no age-associated differences in any of the hemodynamic parameters were determined to be likely. The only significant age-associated difference in response was to graded doses of isoproterenol wherein there was a larger increase in flow and a greater decrease in resistance in the young compared to the senescent dogs. There were no age-associated differences in response to any of the other drugs. Thus, these data are further evidence in an intact circulation for an age-associated decrease in another beta-adrenergically mediated response. PMID- 3347098 TI - Redistribution of lipofuscin in aged neurons induced by colchicine. AB - The effect of a single, 40 micrograms, intracerebroventricular injection of colchicine on the distribution of neuronal lysosomes and lipofuscin granules in aged mice was studied. At the light microscope level we observed that colchicine induced a redistribution of dipeptidyl aminopeptidase II (Dpp II), a lysosomal and lipofuscin granule marker enzyme, from the cell bodies of neurons to the dendrites; cell bodies became depleted of Dpp II while dendrites became enriched with this enzyme. Quantitation of this phenomenon at the electron microscope level demonstrated that colchicine induced a rapid and significant decrease in the density of lysosomes and lipofuscin granules from the somata of neurons whereas in dendrites we observed a significant increase in the density of these organelles. PMID- 3347099 TI - Studies on prolactin-secreting cells in aging rats of different strains. I. Alterations in pituitary histology and serum prolactin levels as related to aging. AB - Serum PRL levels and histologically tumor-free pituitary glands of 91 aging rats of the BN/BiRij strain, the WAG/Rij strain and their F1 hybrid were studied. In rats with pituitary glands without signs of hyperplasia, serum PRL levels were, in comparison to rats of 15-24 months, increased 25-29-month-old female BN/BiRij rats and showed a decline with further aging. This rise and decline during aging correlated with changes in the PRL cell volume density and in ultrastructural signs of their synthetic activity. Rats with hyperplastic pituitaries showed similar age-related changes in serum PRL levels, but these levels were higher. Concerning the hyperplasia, some strain differences were found. In BN/BiRij rats anti-r-PRL positive hyperplasia, and in WAG/Rij and F1 rats, anti-r-PRL negative and anti-r-PRL positive hyperplasia were present. All foci of hyperplasia were negative for anti-ACTH and anti-h-GH. In male rats no age-related changes of serum PRL levels could be established, although a decline of PRL cell volume density in the oldest rats is indicated. We conclude that the absence of a continuous age-related rise of serum PRL levels in our animals is caused by exclusion of animals with pituitary tumors. PMID- 3347100 TI - Rhythmic variations of different hemopoietic cell lines and maturation stages in aging mice. AB - Non-proliferative and proliferative myeloid, and lymphoid and erythroid bone marrow cells were studied in aging female C3H mice. A chronobiological approach was used and mice aged 16, 21 and 26 months were examined vs. 3 month-old mice every 3 h during the 24-h period in three different experiments. Significant circadian fluctuations were observed in most of the cell populations, even in the oldest mice. The rhythmicity patterns might be different at different times of the year, and in young mice seasonal fluctuations in the 24-h mean values were observed. The absolute numbers of the 24-h means seemed to be highest at 21 months of age in all cell lines and maturation stages. Sinus function fitting indicated a decline of the amplitudes in aging mice. Minor age-related phase differences were indicated in some populations. However, the fitting of original data to single sinus functions was variable and often obscured important features in the cell number variations. The present investigation illustrates the importance of performing time-sequence studies in hematology. PMID- 3347102 TI - [Hemophilia and acquired immunodeficiency syndrome]. PMID- 3347101 TI - [Hypertension, antihypertensive treatment and coronary cardiopathy: a call for caution]. PMID- 3347103 TI - [Renal amyloidosis and extra-capillary glomerulonephritis. A rare association]. PMID- 3347104 TI - [Systemic familial therapy in primary medicine]. PMID- 3347105 TI - [Disseminated histoplasmosis in a patient with acquired immunodeficiency syndrome]. PMID- 3347106 TI - [Prevalence of diabetes mellitus in the province of Guadalajara]. PMID- 3347107 TI - [Alcoholic acidosis: diagnostic difficulties]. PMID- 3347108 TI - [Long-lasting febrile syndrome as a manifestation of hyperthyroidism caused by amiodarone]. PMID- 3347109 TI - [Meningoencephalitis and mononucleosis syndrome associated with acute infection by human immunodeficiency virus]. PMID- 3347110 TI - [Tuberculosis in necropsies]. PMID- 3347111 TI - [Intra-parenchymal renal pheochromocytoma]. PMID- 3347112 TI - [Respiratory infections in a general hospital from the perspective of an prospective epidemiologic study]. PMID- 3347113 TI - [Natural history of nephropathy in type I diabetes mellitus]. PMID- 3347114 TI - [Effects of the chronic administration of ketoconazole in patients with hyperandrogenism of adrenal origin]. PMID- 3347115 TI - [Continuous ambulatory registration of arterial pressure with a non-invasive device (Kontron H). Differentiation between mild arterial hypertension and labile normotensives]. PMID- 3347116 TI - [Estimation of sodium intake in elderly patients using a reactive strip]. PMID- 3347117 TI - [Cardiac and pulmonary calcifications caused by massive intake of milk, aluminum hydroxide and calcium polystyrene sulfonate in a patient on hemodialysis]. PMID- 3347119 TI - [Detection of alcoholism in a general hospital]. PMID- 3347118 TI - [Simultaneous rupture of the heart septum and the free wall of the right ventricle in a patient with acute myocardial infarct]. PMID- 3347120 TI - [Case-control studies?]. PMID- 3347121 TI - [Renal failure caused by indomethacin in a patient with adrenal insufficiency]. PMID- 3347122 TI - [Alcohol and auricular fibrillation]. PMID- 3347123 TI - [Pathogenesis of disseminated candidiasis in heroin addicts]. PMID- 3347125 TI - Cardiovascular pharmacotherapy II: Antiarrhythmic and antihypertensive drugs. PMID- 3347124 TI - [Pulmonary nocardiosis as a presenting form of acquired immunodeficiency syndrome]. PMID- 3347127 TI - Child sexual assault and mandatory notification. PMID- 3347126 TI - Helping the frustrated helpers. PMID- 3347128 TI - [Free small intestine transplantation in plastic reconstruction of the oral cavity, pharynx and cervical esophagus. Report of experiences following 3 years of use]. AB - Between August 1984 and August 1987 77 free intestinal grafts were transplanted in our Department of otorhinolaryngology using microvascular anastomoses. These reconstructions were necessary after tumour resections in the oral cavity, in the pharynx, and the cervical oesophagus. Patients, operative technique, perioperative treatment, and complications are described. The definition of oncologic results is still problematic. Only trends have been discovered. In conclusion, complications, functional results, and the advantages of free intestinal grafts are discussed. PMID- 3347129 TI - [Identification of middle ear implants in high-resolution computerized tomography]. AB - As a result of the increase in the use of computed tomography and the possibility of demonstrating very small structures, x-ray diagnosis is becoming more and more important in investigating complications after examined in patients as well as cadaver temporal bones by using high resolution middle ear computed tomography: 1. autologous/allogenic ossicular implants, 2. alloplastic implants made of ceramic, plastic or metal. As can be seen from our investigations the homografts and some of the implants are easily identifiable (autologous/allogenic ossicular implants, Ceravital and Frialit PORP/TORP and metal devices), are only partly identifiable (Fisch-Tef Platinum and Stainless Steel as well as Titan stapes pistons), hardly or not at all identifiable (PORP/TORP and stapes pistons made of plastic, e.g. teflon, silicone, plasti-pore). The same applies to ventilating tubes. Thus the position in the middle ear of metal tubes which have slipped can be seen clearly, whereas plastic tubes cannot be seen so well. It is of clinical importance that prosthesis dislocation is visible in CT so that should complications occur it is better possible to determine whether revision surgery is necessary. As, however, identification of various devices in CT is still not satisfactory, the manufactures must soon fulfil our demands for a contrast agent to be added to prosthesis. PMID- 3347130 TI - [Computerized tomography imaging of choanal atresia]. AB - Choanal atresia is a rare malformation of the nose. If it occurs bilaterally, it may cause life-threatening complications shortly after birth. The disease is mainly diagnosed clinically. Only few cases have been presented and documented by means of radiologic procedures. In particular, CT presentation of this malformation has to our knowledge not been published to date. PMID- 3347131 TI - [Value of computerized tomography in paranasal sinus osteoma]. AB - An example of a frontal ethmoidal osteoma of extreme dimensions in a juvenile of 16 years of age is discussed. We are studying the question whether preoperative diagnosis via CT can supply pointers to the involvement of neighboring tissue structures. PMID- 3347132 TI - [Topography of the round window and its significance for the surgical therapy of perilymph fistulas]. AB - The clinical findings concerning the diagnosis of a rupture of the round window membrane vary widely. Therefore, microtopography of the round window was studied using 45 serially sectioned human temporal bones of the Wittmaack Collection, ENT Clinic, University of Hamburg. Our morphometrical data show a great variety in respect of the dimension of the round window membrane and the angle between the window membrane and the tympanic membrane. The extension and the microtopography of the promontory are as variable as the mucosal folds in the round window niche. It can be concluded that a direct view of the round window membrane is possible only in rare cases. Surgical manipulations to improve the view of the round window should be avoided because of the danger of an iatrogenic lesion of the inner ear. PMID- 3347133 TI - [Tympanoplasty with incus interposition]. AB - We report on a 5-year experience with 44 patients (1980-1985) with incus interposition using a modelled or sculptured incus, either autograft or homograft, to correct ossicular discontinuity when a functional malleus and stapes are present. After a period of 21 months, 75% of our patients achieved an air-bone gap closure between 1 and 10 dB. The postoperative hearing results of patients with trauma and middle ear atelectases were better than the hearing results of patients with cholesteatomas. These long-term results are dependent upon intact malleus attic ligaments and an intact tensor tympani tendon. It is very important that the modelled incus is repositioned under the malleus handle neck. PMID- 3347134 TI - [Immunohistochemical study of the palatine tonsils]. AB - This study reports on an immunohistochemical examination of the tonsils. For this purpose 10 clinically healthy tonsils, 15 with acute tonsillitis, 40 with chronic cryptic tonsillitis and 16 hyperplastic tonsils were studied by means of the direct immunofluorescent technique. With regard to the clinically healthy tonsils: the number, the size of the germinal centres and the density of the immunocytes in them were very large in the hyperplastic tonsils, large in chronic cryptic tonsillitis, but remarkably decreased in acute tonsillitis. The disseminated immunoglobulin of the centres also presented a significant increase in all of them. In the extrafollicular area the fluorescent immunocytes were significantly increased. Although we did not notice differences in the density of IgA and IgM immunocytes between chronic cryptic tonsillitis and hyperplastic tonsils in the acute tonsillitis IgA immunocytes were found to be increased. PMID- 3347135 TI - [A rare nasopharyngeal tumor: Hodgkin's disease]. AB - Primary cases of Hodgkin's disease in the nasopharynx are extremely rare. The authors report on two such cases: A 27 year old male had a large tumour, lined with a smooth mucous membrane, in the nasopharynx. The results of examinations of the neck, thorax, and abdomen were normal. The tumour was removed through the palate. Histological findings confirmed the diagnosis of lymphocyte-prominent Hodgkin's disease (subtype paragranuloma). 11 years ago a nasopharynx tumour was removed by adenotomy from a 57 year old female. A diffuse hyperplasia of the lymphatic tissue was diagnosed at the time. Recently cervical lymph nodes appeared, and a second tumorous lesion was discovered in the nasopharynx. Histological examination of the tumour and cervical lymph node indicated lymphocyte-prominent Hodgkin's disease (subtype paragranuloma). On re-examining histological sections from the tumour removed 11 years ago, the authors again saw the types of change indicative of Hodgkin's disease. The probable course and outcome of lymphocyte-prominent Hodgkin's disease of the nasopharynx, especially of the paragranuloma subtype of the disease, are discussed. Treatment of both patients included adjuvant extended-field radiotherapy. PMID- 3347136 TI - [Prevention of permanent loss of sensation of the external ear following parotidectomy]. PMID- 3347137 TI - Acetylcholine content in superior cervical ganglion following reinnervation of vagal afferent fibers in cat. AB - The superior cervical ganglion (SCG) was reinnervated by vagal afferent fibers by cross anastomosis between the cranial end of nodose ganglion and the caudal end of SCG in cats. Formation of functional synapses was evidenced by unilateral mydriasis and contraction of the nictitating membrane in response to inflation of the stomach with a balloon or to electrical stimulation of the afferent vagus. The acetylcholine (ACh) content in the cross-anastomosed SCG (reinnervated by vagal afferent fibers) was measured. In anastomosed SCG, the ACh content was about half of normal SCG, but significantly higher than chronically decentralized SCG. Also the ACh content in nodose ganglion (NDG) was investigated in situations in which there was anastomosis, chronic supra, infra, or supra-/infranodose vagotomy. The ACh content of anastomosed NDG was near that of supranosdose vagotomized ganglion. The ACh content of supra-/infranodose vagotomized NDG, which can be considered the NDG itself, was as much as that of normal intact NDG. It was found that the ACh content of infranodose vagotomized NDG was increased, possibly the result of vagal efferent axonal flow or transport. The ACh content of vagal trunk with or without infranodose vagotomy was also measured. The ACh content of vagal trunk with infranodose vagotomy was smaller than that of the normal trunk, but there was still a considerable quantity of ACh. There was no significant change in wet weight of the SCG and NDG before or after the operations. From these results we have concluded that the transmission of the cross-anastomosed SCG (reinnervated with vagal afferent nerve) was cholinergic; and that the vagal afferent nerve have afferent cell bodies not only in NDG but also in peripheral vagal trunks (infranodose portion). These results strongly suggest that vagal afferent fibers are in part cholinergic. PMID- 3347138 TI - Prenatal stress increases anxiety related behavior and alters cerebral lateralization of dopamine activity. AB - Effects of unpredictable (random) prenatal stress on the level of anxiety and cerebral lateralization of dopamine turnover rates were studied in rats. The observation of a decrease in the amount of time spent in the open arms of a "plus maze" supported earlier findings of an increased fearfulness to stressful situations in the offspring in adulthood. We also observed elevated rates of dopamine turnover in the right prefrontal cortex and reduced dopamine activity in the right nucleus accumbens and left corpus striatum of the prenatally stressed animals. This resulted in directional shifts of left-right differences in dopamine activity in all 3 areas. These findings indicate that prenatal stress induces permanent alterations in dopaminergic activity and in cerebral asymmetry. We suggest that the changes in cerebral lateralization of dopamine function may underly the increase in reactivity to anxiety-provoking situations in prenatally stressed offspring. PMID- 3347139 TI - A redox system for brain targeted estrogen delivery causes chronic body weight decrease in rats. AB - The effects of 2 redox based carriers for brain directed delivery of estradiol (CDS-E2) and ethinyl estradiol (CDS-EE) on body weight were examined in rats. A single dose of CDS-E2 (3 mg/kg) decreased weight gain in castrate rats for at least 24 days. The dose response of weight gain and LH suppression were compared 12 days and 12 to 25 after CDS-E2 and CDS-EE, respectively, in ovariectomized (OVX) rats. Weight decrease was detected at a lower dose and was significant for longer after drug treatment than LH decrease. Both compounds were more potent than equimolar estradiol or estradiol valerate in reducing weight gain. Intact rats also showed decreased weight gain but were less sensitive to CDS-E2 compared to OVX rats. The effects appeared to be estrogen specific as carrier-linked testosterone had no effect on weight. The mechanisms of sustained and potent drug effects on weight are being explored. PMID- 3347140 TI - Vasopressin neuropeptides and acquisition of heroin and cocaine self administration in rats. AB - The effect of the vasopressin neuropeptide des-glycinamide (Arg8)-vasopressin (DGAVP) on reducing the acquisition of intravenous heroin self-administration in rats was analyzed. When rats reduced in body weight were allowed to self administer heroin for 1 h per day in the presence of a fixed time, non contingent food delivery schedule, it appeared that heroin intake was related in an orderly way to the unit dose of heroin delivered. DGAVP decreased heroin intake during days 4 and 5 of acquisition, especially when a high dose of heroin was delivered. DGAVP decreased heroin intake more effectively when rats were tested without the food delivery schedule and for 6 h instead of 1 h sessions per day. Structure activity relationship studies revealed that the peptide (pGlu4, Cyt6)AVP-(4-8) was the shortest active sequence mimicking the effect of DGAVP and that this peptide was somewhat more potent than DGAVP in this respect. The peptide (pGlu4,Cyt6)AVP-(4-9) increased the heroin intake of the rats. DGAVP and (pGlu4,Cyt6)-AVP-(4-8) also decreased cocaine intake of body weight reduced rats given the opportunity to self-administer cocaine intravenously in daily 6 h sessions. It is concluded that vasopressin neuropeptides may decrease the reinforcing efficacy of heroin and cocaine during acquisition of drug self administration rather than interact with nutritional and environmental factors influencing drug taking behavior. PMID- 3347141 TI - Contribution of adrenal norepinephrine output to increase aortic norepinephrine during carotid sinus reflex activation in anesthetized dogs. AB - Changes in circulating plasma catecholamine (CA: E, epinephrine; NE, norepinephrine; and DA, dopamine) concentrations in aortic (AO) blood were investigated in relation to variable rates of CA secretion from both adrenal (ADR) glands in response to bilateral carotid artery occlusion (BLCO) in vagotomized dogs anesthetized with sodium pentobarbital. During BLCO (3 min), AO systolic pressure (AP) increased along with significant increases in ADR-CA output, renal venous (RV) CA output, as well as in AO-E and NE concentrations. A ratio of NE:E in ADR venous and AO blood did not exceed 0.42 +/- 0.09 and 1.09 +/ 0.24 upon BLCO, respectively. In contrast, the NE:E ratio in RV blood increased significantly from 5.39 +/- 0.91 to 9.78 +/- 1.31. Following adrenalectomy (ADRX), the increase in AO-NE in response to BLCO was significantly attenuated by approximately 56%, but the increase in RV-NE output was not affected by ADRX. The results show that in vagotomized dogs, NE is co-released with E from the adrenal glands upon BLCO. The data also indicate that the increase in AO-NE concentration was dependent to a similar extent on the simultaneous increases in ADR-NE output and neuronal NE release. We conclude that under conditions where the sympathoadrenal system is activated, circulating plasma NE concentration may be significantly affected by an increase in ADR-NE output. Sympathetic neuronal contributions would, thereby, be overestimated in assessing overall sympathetic nerve activity by measuring circulating NE. NE concentrations in local venous effluent from individual organs may be more reliable estimates of the sympathetic nerve activity. PMID- 3347142 TI - Suppressive effect of ipriflavone on bone depletion in the experimental diabetic rat: dose response of ipriflavone. AB - The dose dependent effect of ipriflavone (7-isopropoxy-isoflavone) on the femoral bone in streptozotocin-induced diabetic rats was studied by microdensitometric analysis. Diabetic rats showed severe hyperglycemia, glucosuria, hypoinsulinemia, associated with increased urinary calcium and hydroxyproline. Microdensitometric analysis revealed decreases in femoral length, bone width, and bone density. The dietary administration of ipriflavone (about 270 mg/kg/day) to the diabetic rats for 6 weeks prevented reduction of the cortical thickness index in the diaphysis and depletion of bone density in the distal metaphysis, and also reduced the inner diameter of the diaphysis; diabetic state was not improved. A simple correlation and linear regression analysis revealed that ipriflavone also significantly reduced the inner diameter in the diaphysis at a dose of 90 mg/kg/day, but not at one of 25 mg/kg/day. These results suggest that ipriflavone suppresses the depletion of the femoral bone through inhibition of bone resorption in a dose dependent fashion; its minimum effective dose is 90 mg/kg/day in experimental diabetes. PMID- 3347143 TI - Brain norepinephrine and convulsions in the genetically epilepsy-prone rat: sex dependent responses to Ro 4-1284 treatment. AB - Seizure predisposition in the Genetically Epilepsy-Prone Rat (GEPR) is at least partially dependent on central nervous system noradrenergic deficits. We have previously shown that moderate seizure GEPRs (GEPR-3) experience an increase in seizure severity after receiving Ro 4-1284, a monoamine vesicle inactivating drug. We are now reporting the effect of this drug on severe seizure GEPRs (GEPR 9). Motives for this study were: (a) to determine the effects of further depletion of innately deficient monoaminergic stores on seizure latencies and (b) to investigate whether a previously documented seizure severity difference between the sexes is related to the defective monoaminergic system in these subjects. GEPR-9s with known seizure history were tested for latency to onset of running phase and convulsion 45 minutes after Ro 4-1284 or saline administration. Brain norepinephrine levels were also determined. Ro 4-1284 caused severe depletion of monoamines in all brain areas assayed in both sexes of GEPR-9s and also caused a reduction in the latencies for onset of running and convulsion. The drug-induced norepinephrine depletion across the brain areas surveyed was significantly greater in females than in their male littermates. These observations prompt us to postulate that noradrenergic neurons in female GEPR-9s are functionally different from those in males and that this difference is detected in the differential effectiveness of Ro 4-1284 between the two sexes. Also, the influence of gonadal hormones on seizure predisposition and on the neurochemical actions of Ro 4-1284 may be different in GEPR-9 males and females. PMID- 3347144 TI - The antidysrhythmic effect of metoprolol in the epinephrine treated chick embryo. AB - It was confirmed through electrocardiography that within two hours after epinephrine treatment, four day chick embryos either maintained normal rhythm or developed a severe cardiac dysrhythmia (22/93, 24% dysrhythmic). The ECG dysrhythmia in epinephrine treated embryos were characterized by periods of bradycardia, asystole, and various supraventricular or ventricular dysrhythmias. Within four hours after treatment, dysrhythmic embryos either reestablished normal rhythmicity or died. Electrocardiographic data also demonstrated that metoprolol pretreatment will block epinephrine induced dysrhythmias (0/46, 0% dysrhythmic). We conclude that metoprolol possesses antidysrhythmic properties in the epinephrine treated chick embryo. PMID- 3347146 TI - Cyclosporine increases calcium in kidney medulla. AB - Treatment of rats with 20, 50 or 100 mg/kg of cyclosporine p.o. markedly increased 45Ca accumulation in kidney slices especially in medulla. The effect was related to dose and duration of treatment, and was also observed in slices of kidney medulla from cyclosporine-treated mice. Total calcium was elevated in kidney medulla of cyclosporine-treated rats so that the effect is not merely an increased exchange but a build-up of calcium in the tissue. No histopathologic evidence of cyclosporine-related cell necrosis was present in mouse kidney, showing that calcium accumulation is not dystrophic in character. Accumulation of 45Ca in slices of rat heart, liver, or brain was not affected by cyclosporine pretreatment of the animals. It is suggested that cyclosporine-induced changes in calcium metabolism in kidney medulla may influence kidney function. PMID- 3347145 TI - The human platelet as an independent unit for sulfate conjugation. AB - The human platelets possess a full complement of enzymes capable of synthesizing N-acetyldopamine (NADA) 35sulfate from ATP, Mg++ and sodium 35sulfate. The pH optimum for this three-step overall sulfate conjugation (comprising of the ATP sulfurylase, APS kinase and phenolsulfotransferase reactions) is 8.6 and the reactions proceeded progressively for several hours. Both ATP and Mg++ ions, above their respective optimal concentrations of 5 and 7 mM, inhibited the sulfate conjugation of NADA. The apparent Km values for NADA as determined by the phenolsulfotransferase (PST) and overall reactions were similar in magnitude being 2.6 and 4.8 microM, respectively, while that for sodium 35sulfate was 202 microM. A comparison of these two activities in 62 platelet preparations of normal subjects showed that the rate of the PST reaction was generally higher than the overall reaction even though the PST assay was carried out at suboptimal concentration of PAPS. There was a positive correlation (r = 0.82) between the two sets of data, suggesting that the PST reaction probably has some control over the rate of overall sulfate conjugation. PMID- 3347148 TI - The analgesic defect of C57BL/6J-bgJ/bgJ (beige-J: Chediak-Higashi syndrome) mice transmitted by adoptive transfer of spleen cells to normal littermates. AB - We recently discovered and reported that C57BL/6J-bgJ/bgJ (beige-J) mice have a deficiency in their analgesic response to intracerebroventricularly-administered morphine in the tail-flick test. Postulating a link between these findings and the known immunological defect of beige-J mice (Chediak-Higashi syndrome), we examined the effect of splenectomy on beige-J mice and the adoptive transfer of their mononuclear spleen cells to normal littermate controls (2 x 10(7) cells via tail vein). Eight days after these interventions, the splenectomized beige-J mice responded nearly as well as normal mice to centrally administered morphine in the tail-flick test. The adoptive transfer recipients, in contrast, nearly completely lost their response to the analgesic action of morphine in this test. From the combined results, the spleen appears to be a significant factor in the analgesic defect of beige-J mice and, furthermore, mononuclear splenocytes appear to be the source of a substance that can transfer this defect to otherwise normal animals. PMID- 3347147 TI - Lack of increase in concentrations of cerebrospinal fluid sodium in rats with various stages of DOCA-salt hypertension. AB - Experiments were conducted in conscious rats to determine whether DOCA-salt treatment could cause an elevation of sodium concentration of cerebrospinal fluid (CSF), which may be responsible for the enhanced activity of sympathetic nervous system (SNS) and increased secretion of vasopressin (AVP). Systolic blood pressure (SBP) and mean arterial pressure (MAP) were gradually but consistently increased by DOCA-salt treatment. Serum Na concentration was similarly increased with time by DOCA-salt, and significantly higher than control in the 4th treatment week. In contrast, DOCA-salt did not alter the CSF Na levels at any time during treatment. A relationship between SBP and CSF Na was never evident at any stage of the DOCA-salt hypertension. The decrease in MAP following administration of the vasopressin V1-receptor antagonist, d(CH2)5Tyr(Me)AVP (30 micrograms/kg), or hexamethonium (30 mg/kg) was enhanced in the DOCA-treated rats, as compared to findings in the controls. These hypotensive effects were gradually, but progressively enhanced with the development of hypertension by DOCA-salt treatment. We tentatively conclude that mechanisms accounting for the enhanced activity of SNS and AVP in DOCA-salt hypertensive rats are independent of an increased Na concentration in the CSF. PMID- 3347150 TI - Hypnosis and reincarnation experiences. PMID- 3347151 TI - The diabetic school child. PMID- 3347152 TI - Heart Rx: a new tool for physicians. PMID- 3347149 TI - Alteration in the disposition and metabolism of S(-)-propranolol in rats with active respiratory viral infection. AB - Viral illness elicited marked changes in the disposition and metabolism of S(-) propranolol in rats during the course of a recent viral outbreak in our rodent colony. A slower rate of gastrointestinal absorption and a much higher clearance of orally-administered S(-)-propranolol were observed. The apparent increase in metabolic clearance is partly attributed to a decrease in the serum protein binding of S(-)-propranolol. A direct stimulation of microsomal oxidative metabolism was also suggested by an increase in urinary recovery of the monohydroxyl metabolites of S(-)-propranolol. In addition, a greater portion of the phenolic metabolites were present in urine as the glucuronic acid conjugates, which may be explained by a concomitant stimulation in conjugative reaction. These observations are unusual in that existing reports indicate that viral illness in man and animals generally leads to an inhibition of oxidative drug metabolism. PMID- 3347153 TI - Will your prescribing habits cost your license? PMID- 3347154 TI - Elective repeat cesarean section: old controversy, new concepts. PMID- 3347155 TI - Eosinophilic meningitis. PMID- 3347156 TI - Maryland's approach to regulating physician office laboratories. PMID- 3347157 TI - Counter-counterpoint: scan! PMID- 3347158 TI - Breast cancer booklet: a backward step in therapy. PMID- 3347159 TI - Focusing on medical informatics. PMID- 3347160 TI - Modeling hospital information systems with Petri Nets. PMID- 3347161 TI - Treatment of uncertainty in an oncology protocol by probabilistic and artificial intelligence approaches. PMID- 3347162 TI - Persons and computers in medicine and health. PMID- 3347163 TI - A nonparametric law of initial values (LIV) test for comparing spreads in two paired samples. PMID- 3347164 TI - Influence of sampling variation and analytical errors on the performance of the multivariate reference region. PMID- 3347165 TI - The challenge of "gatekeeping". PMID- 3347167 TI - MSMS: taking the lead in AIDS education. PMID- 3347166 TI - Tuberculosis and AIDS. PMID- 3347168 TI - MSMS: taking the lead on AIDS. PMID- 3347169 TI - Interviews shed light on AIDS. PMID- 3347170 TI - MSMS members have new group health option. PMID- 3347171 TI - New licensure rules. PMID- 3347172 TI - Promoting nursing as a profession: a community hospital campaign. PMID- 3347173 TI - Evidence to the review body for nursing staff, midwives, health visitors and professions allied to medicine for 1988. The national shortage of midwives is the most serious crisis at this time. PMID- 3347174 TI - Response from the inner city. PMID- 3347176 TI - A consumer view of birth preparation classes: attitudes of a sample of working class primiparae. PMID- 3347175 TI - Cowgate Neighbourhood Centre--a preventative health care venture shared by midwives and social workers. PMID- 3347177 TI - The financial dimensions of affaires de coeur: bridging the chasm between medicine and economics. PMID- 3347178 TI - Entrepreneurial dangers. PMID- 3347179 TI - Shopping for statistics. PMID- 3347180 TI - The Western Sydney Health Study: results of the shopping-centre survey. AB - The Western Sydney Health Study is a two-phase descriptive study that is designed to provide data on the health-related knowledge, attitudes and behaviour of persons in the Western Metropolitan health region, which has higher-than-average death rates of many disorders that are associated with life-style. In the first phase of the study, 2164 respondents were interviewed in six shopping centres in the region. The prevalence rates of self-reported cardiovascular disease and diabetes were about twice those that were found in the Australia-wide National Heart Foundation Risk Factor Prevalence Study in 1983. The prevalence rates of smoking and self-reported raised blood lipid levels were also high. Doctors and nurses were the main sources of health information, and the media was less important as a source of health information than was found in the Better Health Commission's national survey in 1985. Over 80% of respondents believed that a lowering of the dietary fat intake and an increase in exercise were health enhancing behaviours. Given this high level of health knowledge, the major aims for health promotion in the region should be a social change to facilitate choices towards healthy behaviour and the provision of skills to enable individual behavioural changes. PMID- 3347181 TI - Dissatisfaction in general practice: what do patients really want? AB - In 31 general practices in Adelaide, approximately 100 consecutive adult patients aged 15-64 years completed a 21-item questionnaire that related to their dissatisfaction with aspects of the care that was provided in the practice. Fourteen of the practices were "solo" practices, five practices were two-person partnerships and 12 practices involved three or more partners. The 21 items divided naturally into five groups: "architecture", "receptionists", "accessibility", "quality" and "communication". Factor analysis of the responses provided support for the idea that "receptionists", "accessibility" and "communication" were independent issues for the respondents and that "quality" was less discrete and was embedded in a factor which we have labelled "mechanics". For nearly all items, the mean dissatisfaction values for the practices were greatest in the larger practices and least in the two-person practices, with solo practices occupying an intermediate position. The main dissatisfaction related to accessibility and communication. These issues are explored in the light of current trends in the organization of primary medical care. PMID- 3347182 TI - The impact of the "grim reaper" national AIDS educational campaign on the Albion Street (AIDS) Centre and the AIDS Hotline. AB - The national educational programme on the acquired immunodeficiency syndrome (AIDS) caused a dramatic increase in the number of heterosexual persons who presented for human immunodeficiency virus (HIV) antibody testing at the Albion Street (AIDS) Centre. There was also a marked increase in the number of intravenous drugs abusers who presented, although the proportion of this high risk group that has been tested remains low. There was no increase in the number of homosexual men who presented for testing. The increase in the number of telephone calls that were received by the Centre's AIDS Hotline was due to an interest in HIV-antibody testing, rather than an interest in information about safer sexual practices. The campaign was seen to have achieved its primary objective, namely, to alert sexually-active persons of the potential spread of the virus from the high-risk groups. However, it is clear that future educational campaigns need to target specific high-risk groups such as intravenous drug abusers. PMID- 3347183 TI - Colour-coded imaging of cardiac blood flow. PMID- 3347184 TI - Urinary incontinence secondary to prazosin. PMID- 3347185 TI - The paradigm shift in blood transfusion. PMID- 3347186 TI - Adult epiglottitis. AB - Adult epiglottitis is a disease that is well known to otolaryngologists, but is less commonly encountered in general medical practice. It is being recognized with increasing frequency, and in many respects is different from paediatric epiglottitis. Three patients with adult epiglottitis are described, with an emphasis on the variation in clinical presentation and the difficulty in diagnosis. The appropriate examinations and the management of the disease are discussed. PMID- 3347187 TI - Waiting for Margaret. PMID- 3347188 TI - Prescribing habits of a sample of Victorian general practitioners. PMID- 3347189 TI - AIDS-related risk-taking behaviour in drug abusers. PMID- 3347190 TI - Pasteurella multocida vertebral osteomyelitis. PMID- 3347191 TI - Performance of final-year students. PMID- 3347192 TI - Breast weight and hand paraesthesiae. PMID- 3347193 TI - Clinical competence. PMID- 3347194 TI - Non-accidental injuries by fathers. PMID- 3347196 TI - Cytosolic calcium management, regulation and biologic significance in epithelial tissue. PMID- 3347195 TI - Lightning deaths. PMID- 3347197 TI - Newborn screening for inherited metabolic disease: principles and practice. PMID- 3347198 TI - Using guilt constructively in the NICU to affirm parental coping. PMID- 3347200 TI - Life, money, quality: the impact of regionalization on perinatal/neonatal intensive care. PMID- 3347201 TI - The role of the community hospital nurse in supporting parents of transported infants. PMID- 3347202 TI - Acquired immune deficiency syndrome in the neonate. PMID- 3347199 TI - Discharge teaching in the NICU: the changing needs of NICU graduates and their families. PMID- 3347203 TI - Guide to lobbying. PMID- 3347204 TI - A Chinese hamster ovary cell line hypersensitive to ionizing radiation and deficient in repair replication. AB - An X-ray-sensitive Chinese hamster ovary cell line was isolated by means of a semi-automated procedure in which mutagenized cells formed colonies on top of agar, were X-irradiated, and were photographed at two later times. We compared the photographs to identify colonies that displayed significant growth arrest. One of the colonies identified in this manner produced a stable line (irs1SF) that is hypersensitive to ionizing radiation. The X-ray dose at which 10% of the population survives (D10) is 2.25 Gy for irs1SF and 5.45 Gy for the parental line. The new mutant is also moderately sensitive to ethyl methanesulfonate. irs1SF performs only half as much X-ray-induced repair replication as the parental line, indicating a defect in excision repair. This defect is believed to be the primary cause of the line's radiosensitivity. Although irs1SF repairs DNA double-strand breaks at a normal rate, it repairs single-strand breaks more slowly than normal. irs1SF has an elevated number of spontaneous chromatid aberrations and produces significantly higher numbers of X-ray-induced chromatid aberrations after exposure during the G1 phase of the cell cycle. The line is hypomutable, with X-ray exposure inducing only one-third as many 6-thioguanine resistant colonies as the parental line. PMID- 3347205 TI - Transfection of the cloned human excision repair gene ERCC-1 to UV-sensitive CHO mutants only corrects the repair defect in complementation group-2 mutants. AB - The human DNA-excision repair gene ERCC-1 is cloned by its ability to correct the excision-repair defect of the ultraviolet light- and mitomycin-C-sensitive CHO mutant cell line 43-3B. This mutant is assigned to complementation group 2 of the excision-repair-deficient CHO mutants. In order to establish whether the correction by ERCC-1 is confined to CHO mutants of one complementation group, the cloned repair gene, present on cosmid 43-34, was transfected to representative cell lines of the 6 complementation groups that have been identified to date. Following transfection, mycophenolic acid was used to select for transferants expressing the dominant marker gene Ecogpt, also present on cosmid 43-34. Cotransfer of the ERCC-1 gene was shown by Southern blot analysis of DNA from pooled (500-2000 independent colonies) transformants of each mutant. UV survival and UV-induced UDS showed that only mutants belonging to complementation group 2 and no mutants of other groups were corrected by the ERCC-1 gene. This demonstrates that ERCC-1 does not provide an aspecific bypass of excision-repair defects in CHO mutants and supports the assumption that the complementation analysis is based on mutations in different repair genes. PMID- 3347206 TI - Six complementation groups for ionising-radiation sensitivity in Chinese hamster cells. AB - The ionising radiation-sensitive mutants irs 1, irs 2, irs 3, xrs-1 (or xrs-7), EM7 and XR-1 were fused to wild-type cells or to each other in pairs to create hybrid cells. These hybrids were checked chromosomally and their X-ray sensitivity tested. Each mutant was found to be recessive to wild-type and to complement the X-ray sensitivity of the other mutants. Thus there appear to be at least 6 complementation groups for ionising radiation sensitivity in Chinese hamster cells. PMID- 3347207 TI - Aberrant DNA repair and enhanced mutagenesis following mutagen treatment of Chinese hamster Ade-C cells in a state of purine deprivation. AB - Ade-C is a Chinese hamster ovary cell line auxotrophic for purines because of a mutation in the de novo synthetic pathway. We now show that, in the absence of exogenous hypoxanthine, replicative DNA synthesis is rapidly shut down. Various aspects of DNA repair have been studied in purine-starved cells. Incision, the first step of excision repair of UV damage, appears normal, as do the later steps, repair synthesis (demonstrated following chemical damage as well as UV irradiation) and ligation. However, removal of UV-induced pyrimidine dimers is not detected, and it seems that the repair that occurs is aberrant. This behaviour is associated with an increase in cell killing by UV light, and a several-fold increase in the frequency of mutations induced by UV. PMID- 3347208 TI - Excision repair of UV damage in human fibroblasts reversibly permeabilized by lysolecithin. AB - We have examined nucleotide excision repair synthesis in confluent human diploid fibroblasts permeabilized with lysolecithin. Following a UV dose of 12 J/m2, maximal incorporation of [alpha 35S]dNTPs occurred at a lysolecithin concentration (approximately 80 micrograms/ml) where slightly more than 90% of the cells were initially permeable to trypan blue. However, autoradiography of cells, permeabilized at this lysolecithin concentration, demonstrated that only about 20% of the total cell population incorporated significant levels of 35S into DNA. This result presumably reflected the fact that approximately 20% of the total cell population remained permeable for much longer periods of time (up to 2 h) than the remaining cell population (less than 20 min). The incorporation of dNTPs by UV-irradiated, permeabilized cells appeared to be bona fide excision repair synthesis since: (1) Incorporation was completely absent in unirradiated, permeabilized cells and in irradiated, permeabilized repair-deficient cells. (2) Nucleotides incorporated in the presence of BrdUTP were associated with normal density DNA. (3) The apparent Km for all 4 dNTPs was 50-100 nM, in agreement with past reports on human fibroblasts irreversibly permeabilized by cell lysis. (4) DNA associated with the newly incorporated dNTPs underwent ligation and rearrangements in chromatin structure analogous to what is observed in intact human cells. Repair incorporation of dNTPs was rapid and linear during the first 2 h after UV irradiation and permeabilization. After this time, incorporation ceased or continued at a much slower rate. Cell viability experiments and autoradiography demonstrated that the cells permeabilized to [3H]dNTPs were capable of carrying out DNA replication and cell division. Thus, confluent human diploid fibroblasts can be reversibly permeabilized to labeled dNTPs by lysolecithin for the study of excision repair following physiologic doses of UV radiation. However, under these conditions, only a fraction of the cells remain permeable for an extended period of time. PMID- 3347209 TI - Kinetic analysis of UV-induced incision discriminates between fibroblasts from different xeroderma pigmentosum complementation groups, XPA heterozygotes and normal individuals. AB - The capacity of a variety of human fibroblasts to incise DNA following exposure to far ultraviolet-light is determined from the rate of single-strand DNA break accumulation in the presence of DNA synthesis inhibitors. We have quantitated incision, one of the early steps in the UV excision repair pathway, in cells form normal, xeroderma pigmentosum groups C, D, G, H and variant individuals, and in the parents of one XPA patient. On the basis of the estimated initial rates of incision the different XP cells examined in this work can be ranked as follows: XP variant much greater than XPH greater than XPH greater than XPD greater than XPC greater than XPG greater than XPA. In each cell strain breaks accumulate immediately after irradiation over a range of 0.5-20 Jm-2 with the exception of the XPC strain examined, where there is an initial delay of 15 min. The rate of incision in XPA heterozygote cells is roughly half that of normal fibroblasts. Analysis of the kinetics of break accumulation over short intervals after irradiation permits estimation of the apparent enzymatic parameters, Km and Vmax, for the incision step. The approximate values of Km and Vmax for normal and XP variant are similar while for the heterozygotes of an XPA individual Km values are normal (around 1 Jm-2), but there is only half the amount of normal enzyme activity. XPD and H cells express low levels of active enzyme, between 5 and 15% of that of the normal, but while the Km of XPH is very similar to that of normal cells, that of two XPD strains examined is between 2- and 3-fold higher. PMID- 3347210 TI - Human monitoring. PMID- 3347212 TI - International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication no. 14. Considerations for population monitoring using cytogenetic techniques. PMID- 3347211 TI - A pilot study of the use of placental cord blood samples in monitoring for mutational events. AB - A pilot study exploring the examination of placental cord blood samples for mutant proteins with one-dimensional electrophoretic techniques is described. Although technical advances are such that the techniques employed in this study are now partially superceded, the practical problems encountered in this study would be typical of any monitoring program of this type. No mutations altering electrophoretic mobility among a battery of 51 different locus products were encountered in a total of 277,747 locus tests. When these data are combined with similar data from other studies, the mutation rate for electromorphs becomes 0.34 X 10(-5)/locus/generation. PMID- 3347213 TI - Chromosome aberrations, mitogen-induced blastogenesis and proliferative rate index in peripheral lymphocytes from 106 control individuals of the U.K. population. AB - Blood samples were taken from 106 individuals (73 males and 33 females) and examined for chromosome aberrations, mitogen-induced blastogenesis and proliferative rate index (PRI). The values obtained were investigated in relation to sex, age, smoking, alcohol consumption and X-ray exposure. In all the parameters, there was shown to be a difference between the mean values for the males and females. The incidence of chromosome aberrations was greater in females than in the males, whereas the mean values of PRI and mitogen-induced blastogenesis were lower in females than in the males. A sex difference has been reported previously in the same population, in that the females were shown to have a higher rate of sister-chromatid exchanges than the males (Anderson et al., 1986; Dewdney et al., 1986). Contraceptive pill usage was not considered to be of importance in the sex difference seen and there was shown to be no significant influence due to age, smoking or alcohol consumption on any of the parameters except that smoking reduced lymphocyte PRI. Males with previous X-ray exposure also showed a lower response to mitogen-induced blastogenesis and had a reduced PRI. PMID- 3347214 TI - Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. AB - In order to assess the potential of cytogenetic determinations on peripheral blood lymphocytes as a means of monitoring human populations subject to low level occupational and environmental exposures to chemical mutagens and carcinogens, accurate baseline data are required. Accordingly, we have determined mean frequencies of chromosomal aberrations and of sister-chromatid exchanges, their variances, and the sources of this variance in a cohort of 353 healthy employees of the Brookhaven National Laboratory. A detailed protocol was adopted for blood sampling, lymphocyte culture, cytogenetic preparation and scoring in order to minimize variation from these potential sources. Scoring was divided between the Oak Ridge and the Brookhaven groups with duplicate scoring sufficient to evaluate and minimize the effect of any differences between laboratories or between individual scorers. In all, the data include 71,950 cells scored for chromosomal aberrations and 16,898 cells scored for sister-chromatid exchanges. The mean unadjusted frequency of sister-chromatid exchanges was 8.29 +/- 0.08/cell. As reported in other studies, cigarette smoking very significantly influenced sister chromatid exchange frequencies; in our study the mean for smokers was 9.0 +/- 0.2, while that for non-smokers was 8.1 +/- 0.1/cell. The mean frequency was statistically higher in females than in males, regardless of smoking status. On the other hand, age of the subject did not significantly influence sister chromatid exchange frequencies. Curiously, the subject's total white cell count did influence sister-chromatid exchange frequency. No other source of variation was found. The frequencies of chromosomal aberrations of all types were determined. The frequency of the most common unequivocal chromatid type, the chromatid deletion, was 0.81 +/- 0.05%, that of the most common unequivocal chromosome type, the dicentric, was 0.16 +/- 0.02%. No statistically significant influence was found of age or sex, nor of any other parameter tested, on the frequency of any chromosomal aberration type, with the single exception of long acentric fragments, often "supernumerary", believed to represent X chromosomes precociously separated at the centromere. Such fragments were significantly more frequent in samples from females than those from males, and showed a significant positive regression on age. PMID- 3347215 TI - Variation in the human lymphocyte sister-chromatid exchange frequency: results of a long-term longitudinal study. AB - The variation in lymphocyte sister-chromatid exchange (SCE) frequency as a function of time was investigated in nonsmokers and smokers. The smokers were divided into 3 groups depending on their smoking status. The group termed 'smokers' participated in a program to stop smoking but did not reduce or eliminate their use of tobacco; 'smoke enders' successfully completed the smokending program and remained free of tobacco for the duration of the study, while the 'variable' group stopped smoking for a limited time but then resumed smoking. 8 or more blood samples per person were obtained over a period of at least 12 months. The SCE frequencies for each of these groups were compared with each other and with those of two previous longitudinal study groups from our laboratory. The proportion of high-frequency cells (HFCs) was also determined for each sample. The results confirm our previous finding that SCE frequencies and the proportion of HFCs observed in separate samples from the same individual are more likely to be different as the time between samples increases. We also show that smokers have significantly more SCEs and HFCs than do nonsmokers, that SCE frequencies in smokers do not decline for at least 12 months when smoking is stopped, and that among smokers, significant seasonal variation in the SCE frequency occurs. These results provide useful information concerning the effects of smoking upon SCE frequencies, and will be helpful in designing and interpreting the results of long-term human population cytogenetic studies. PMID- 3347216 TI - Cytogenetic monitoring of industrial populations potentially exposed to genotoxic chemicals and of control populations. AB - Currently the most applied technique for monitoring biological effects of exposure to genotoxic chemicals in industrial workers is the measurement of chromosome aberrations in peripheral blood lymphocytes. In the Shell petrochemical complex in The Netherlands cytogenetic monitoring studies have been carried out from 1976 till 1981 inclusive, in workers potentially exposed to a variety of genotoxic chemicals, i.e. vinyl chloride, ethylene oxide, benzene, epichlorohydrin, epoxy resins. Average exposure levels to these chemicals were well below the occupational exposure limits. Results of these studies indicate that no biologically significant increase in the frequencies of chromosome aberrations in the exposed populations occurred compared with control populations. Our experience with this methodology has shown that the results of chromosome analyses are difficult to interpret, due to the variable and high background levels of chromosome aberrations in control populations and in individuals. It is concluded that the method is not sufficiently sensitive for routine monitoring of cytogenetic effects in workers exposed to the low levels of genotoxic compounds. PMID- 3347217 TI - Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals. AB - The aims of the study were to clarify potential exposure situations to anticancer agents during industrial processing, drug manufacture and hospital administration, using cyclophosphamide (CP) as the model compound. CP is considered an animal and human carcinogen, and it is shown to be an indirect mutagen in various test systems using several genetic endpoints. Environmental monitoring was performed by collecting ambient air samples during the different processing and handling stages. Both stationary and personal sampling was used. CP was analyzed by liquid chromatography (HPLC) and mass spectrometry (MS). The process materials and intermediates were also analyzed for genotoxic activity using the Ames test and SCE induction in CHO cells as endpoints. Biological monitoring studies were performed on 147 persons representing 5 groups of workers, control subjects and patients. In the experimental part of the project, the intermediates in the CP manufacturing process, CP I (nor-nitrogen mustard) and CP II (phosphoroxydichloride mustard) were found directly active in the 2 genotoxicity tests. These findings led to improvements in work hygiene when handling CP I and CP II in the process. The CP measurements showed that the highest potential-exposure sites occurred during specific operations of the process, e.g., during emptying of the drying drum and during tablet mass preparation (the range of CP concentrations in air was 0.16-0.49 mg/m3). The correlation between indirect genotoxicity and chemical analyses of the ambient air samples was good, revealing the activity to be due to cyclophosphamide. However, the air samples were found mutagenic without metabolic activation also in the beginning of the process; this is obviously due to CP II particles in the ambient air, since no CP was detected chemically. The personal protection of workers in the plant collaborating in the study is efficient and the production unit is equipped with the best available techniques to protect both the personnel and the quality of the drug. Both the urine mutagenicity analyses using strain TA1535 of Salmonella typhimurium as indicator and the cytogenetic analyses of peripheral blood lymphocytes using sister-chromatid exchanges or structural chromosomal aberrations as endpoints were negative. However, a statistically nonsignificant trend in increased number of micronuclei was observed in binucleated lymphocytes of the worker groups as compared with controls. The studies on the hospital use of CP were performed in 3 oncological units and 1 pharmacy unit.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3347218 TI - Elevated frequencies of 6-thioguanine-resistant lymphocytes in multiple sclerosis patients treated with cyclophosphamide: a prospective study. AB - An autoradiographic assay for 6-thioguanine-resistant (TGr) lymphocytes was used to determine the frequency of in vivo derived variant T lymphocytes in peripheral blood from multiple sclerosis (MS) patients treated with monthly intravenous infusions of 750 mg/m2 of cyclophosphamide (CP). To analyze the time-course of response to CP, the MS patients were studied prospectively. Samples were obtained from the patients before the beginning of CP therapy, 4-5 times during the course of treatment, and, finally, 2 or 3 months after the completion of therapy. 2 weeks after the first CP infusion, the variant frequencies (Vfs) of the MS patients were significantly increased (p less than 0.05) above their pre treatment values, but by 4 weeks following the first CP infusion the Vfs had fallen to normal or near-normal levels. After subsequent treatments, the frequencies of variant TGr cells were again higher than pre-treatment Vfs. However, within 7-13 weeks after the cessation of CP therapy, the Vfs of all subjects had returned to normal levels. The transient nature of the response indicates rapid in vivo selection against CP-induced TGr mutant cells. The mean pre-treatment Vf of the 4 MS patients who were cigarette smokers was 6.56 X 10( 6) which was significantly greater (p less than 0.05) than the mean Vf (1.52 X 10(-6) of the 4 MS patients who were non-smokers. The mean Vf from 8 assays of healthy non-smokers was 1.92 X 10(-6). PMID- 3347219 TI - Methylations in human hemoglobin. AB - Levels of N-Methylvaline (MeVal) and N tau-methylhistidine (MeHis) were measured in male smokers and non-smokers in a program aimed at mapping background alkylations of hemoglobin (Hb) as potential indicators of doses of exogenous and endogenous genotoxic agents. MeVal was also determined in Hb from rats, Syrian golden hamsters, mice and chickens. MeVal was found to occur at levels around 0.5 nmole/g Hb, with relatively little variation between individuals and species. MeVal was not significantly affected by smoking. This result contrasts with elevated levels of N-hydroxyethylvaline (HOEtVal) measured in the same persons (Tornqvist et al., 1986b). Levels of S-methylcysteine (MeCys) (Bailey et al., 1981) and MeHis were much higher than those of MeVal. The high levels of MeCys and MeHis may be due partly to misincorporation during protein synthesis and to artifacts. S-Adenosylmethionine and formaldehyde are possible endogenous sources of MeVal. One individual (smoker) out of 21 selected for measurement of MeVal was an outlier, with raised levels of both MeVal and HOEtVal, as would be expected in case of a defective detoxification system. PMID- 3347220 TI - Monitoring occupational exposure to carcinogens: detection by 32P-postlabelling of aromatic DNA adducts in white blood cells from iron foundry workers. AB - Blood samples were volunteered by workers in a Finnish iron foundry who were occupationally exposed to polycyclic aromatic hydrocarbons and from control subjects not known to be occupationally exposed to this class of chemical carcinogens. DNA was isolated from peripheral white blood cells and digested with micrococcal nuclease, spleen phosphodiesterase and nuclease P1. The DNA digest was then incubated with [gamma-32P]ATP and polynucleotide kinase. Aromatic adducts present in the digest that were resistant to nuclease P1 were thus 32P labelled while unmodified nucleotides were not. The 32P-labelled adducts were resolved by t.l.c. and detected by autoradiography. Foundry workers were classified as belonging to high, medium or low exposure groups according to their exposure to airborne benzo[a]pyrene (high greater than 0.2, medium 0.05-0.2, low less than 0.05 microgram BP/m3 air). Aromatic adducts were found to be present in DNA from 3/4 samples from the high exposure group, 8/10 samples from the medium exposure group. 4/18 samples from the low exposure group and 1/9 samples from the unexposed controls. The levels of adducts found in the high and medium group samples ranged up to 1 adduct in 10(7) nucleotides but the levels formed in the low exposure group samples were not significantly different from those in unexposed controls. No differences related to the smoking habits of the subjects were observed. Most of the DNA adducts detected had chromatographic mobilities distinct from those formed when the 7,8-diol 9,10-oxide of BP reacted with DNA. The results indicate that highly-exposed individuals are more likely to contain aromatic DNA adducts in their white blood cells, but large interindividual variations were evident. In addition, multiple samples from the same subjects indicate that qualitative and quantitative changes in adduct patterns occur with time. This pilot study suggests that 32P-postlabelling may be useful in monitoring human exposure to known and to previously unidentified environmental genotoxic agents. PMID- 3347221 TI - Genetic and environmental influences on premature death in adult adoptees. AB - To assess genetic and environmental influences on adult mortality, we followed 960 families that included children born during the period 1924 through 1926 who were placed early in life with adoptive parents unrelated to them. We evaluated the risks of dying from all causes or from specific groups of causes between the ages of 16 and 58 years for adoptees with a biologic or adoptive parent who died of the same cause before the age of either 50 or 70. We compared these risks with the adoptees' risk of dying from the same causes between the ages of 16 and 58 when either the biologic or adoptive parents were still alive at the ages of 50 and 70. The death of a biologic parent before the age of 50 resulted in relative risks of death in the adoptees of 1.71 (95 percent confidence interval, 1.14 to 2.57) for all causes, 1.98 (1.25 to 3.12) for natural causes, 5.81 (2.47 to 13.7) for infections, 4.52 (1.32 to 15.4) for cardiovascular and cerebrovascular causes, and 1.19 (0.16 to 8.99) for cancers. The death of an adoptive parent resulted in relative risks of death in the adoptees that were close to unity for all causes, natural causes, and infections, 3.02 (0.72 to 12.8) for vascular causes, and 5.16 (1.20 to 22.2) for cancers. A similar but weaker pattern was observed when either a biologic or adoptive parent died before the age of 70. We conclude that premature death in adults has a strong genetic background- especially death due to infections and vascular causes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3347222 TI - Academic promotion at a medical school. Experience at Johns Hopkins University School of Medicine. AB - We studied promotions at Johns Hopkins University School of Medicine to determine whether clinician-teachers are less likely to be promoted or are promoted later in life than researchers and whether those who are promoted have more articles published than those who are not promoted. Over a five-year period, 93 percent of candidates for the rank of associate professor and 79 percent of the candidates for the rank of professor were promoted. There were no significant differences between clinical and research faculty members in terms of the probability that they would be promoted or their age at promotion to either associate professor or professor. Despite these findings, the responses to a questionnaire indicated that former faculty members perceived clinician-teachers as less likely than researchers to be promoted. Those who were promoted had had about twice as many articles published in peer-reviewed journals as those who were not promoted. We recommend improved counseling of medical school faculty members and more extensive discussion of the criteria for promotion and the chances of academic success. PMID- 3347223 TI - The role of thyroid-stimulating antibodies of Graves' disease in differentiated thyroid cancer. PMID- 3347224 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 12-1988. A 72-year-old man with headaches and multiple cranial nerve palsies. PMID- 3347225 TI - Nature, nurture, and family predisposition. PMID- 3347226 TI - The Libby Zion case. One step forward or two steps backward? PMID- 3347227 TI - The impact of long working hours on resident physicians. PMID- 3347228 TI - Compounding the error. PMID- 3347229 TI - House-staff training--the need for careful reform. PMID- 3347230 TI - Smoking and cancer of the ovary. PMID- 3347231 TI - Maternal hematologic status and outcome of pregnancy in blacks and whites. PMID- 3347232 TI - Sickle-cell trait as a risk factor for sudden death in physical training. PMID- 3347233 TI - Disappearance of trisomy 8 after alpha-2 interferon in a patient with myelodysplastic syndrome. PMID- 3347235 TI - Searle's "Patient Promise". PMID- 3347234 TI - Cyclosporine-associated central nervous system toxicity. PMID- 3347237 TI - Surgical stapling is put in perspective. PMID- 3347236 TI - Evaluating standards of care. PMID- 3347238 TI - Diathermy--how safe is it? PMID- 3347239 TI - Thermoluminescence in irradiated foodstuffs. PMID- 3347240 TI - Avoiding jet lag again. PMID- 3347241 TI - Novel databases for molecular biology. PMID- 3347242 TI - Roaring and oestrus. PMID- 3347243 TI - AIDS commission report confounds critics. PMID- 3347244 TI - Lowering the high risks of bad blood. PMID- 3347245 TI - West German AIDS research programme still in limbo. PMID- 3347246 TI - US health insurance companies screen applicants for AIDS. PMID- 3347248 TI - Call for international treaty to protect genetic diversity. PMID- 3347247 TI - Developmental plasticity in the visual and auditory representations in the mammalian superior colliculus. AB - Environmental factors play an important role in certain aspects of the development of sensory systems. But the way in which the maturation of different sensory modalities is coordinated is poorly understood. We have investigated this question neurophysiologically in the mammalian superior colliculus (SC), which contains topographically aligned maps of visual and auditory space. We report here that an essentially normal auditory map, in approximate register with the visual map, is found in the SC of adult ferrets reared with abnormal binaural localization cues. Also, if, early in life, one eye is deviated laterally, there is a compensatory shift in the auditory map, but early eye rotation totally disorders the auditory representation. These results imply that development of the auditory map is affected by visual activity or by information about eye position and that there is definite, but limited, capacity for the auditory map to reorganize so that it remains aligned with the visual map. PMID- 3347249 TI - US congress hears the good news on Chinese food. PMID- 3347250 TI - Myth, science and art of Greek peonies. PMID- 3347251 TI - Anomalous properties of adenine.thymine tracts. PMID- 3347252 TI - Visual search for a conjunction of movement and form is parallel. AB - Treisman has proposed when a human subject performs a visual search, the search is parallel for targets defined by a single feature, and serial for targets defined by a conjunction of features. Here we report that this is not true for targets defined by a conjunction of the features movement and form. Detection of a moving X among randomly distributed moving Os and static Xs is parallel. Search is uninfluenced by the stationary stimuli despite their spatial intermingling with the moving items. Thus, attention can be restricted to a spatially dispersed perceptual group, defined by common movement. This contradicts previous conclusions from visual search experiments that attention can only be assigned to contiguous regions of visual space. The search process first segregates the array into moving and stationary items, and then examines the moving group for the target form. Cells in the middle temporal region (cortical area MT) have the properties required to perform these operations. PMID- 3347253 TI - Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. AB - Proto-oncogenes encode proteins with three main sites of action: the cell-surface membrane, the cytoplasm and the nucleus. Although the exact biochemical function of most proto-oncogene products is not understood, several of them are known to be involved in signal transduction. A role in gene regulation through DNA binding has been suggested for a recently isolated member of the group of oncogenes acting at the nucleus, v-jun. The C-terminus of the putative v-jun-encoded protein is similar in sequence to the C-terminus of the yeast transcriptional activator GCN4 (refs 8, 9), which forms its minimal DNA-binding domain. GCN4 binds to specific sites whose consensus sequence is highly similar to the recognition sequence of the mammalian transcriptional activator AP-1 (refs 12, 13). Like GCN4, AP-1 binds to promoter elements of specific genes and activates their transcription. Because of the similarity between the recognition sites for GCN4 and AP-1, we examined the possibility that AP-1 could be the product of the c-jun proto-oncogene. The experimental results reported here indicate that the JUN oncoprotein is a sequence-specific transcriptional activator similar to AP-1. PMID- 3347254 TI - Translational activation of the lck proto-oncogene. AB - The lck proto-oncogene, a member of the src gene family, encodes a lymphocyte specific protein tyrosine kinase (p56lck) that is implicated in the pathogenesis of lymphoid neoplasia. We report here that 5' lck sequence elements, containing AUG codons, significantly reduce the in vivo efficiency of p56lck translation from the normal messenger RNA. This result provides a quantitative explanation for the overexpression of p56lck in two retrovirally-induced murine lymphomas that express abnormal lck transcripts from which the physiological 5' translational control region has been deleted and non AUG-containing viral sequences substituted. In contrast to other mammalian genes, most proto-oncogenes contain AUG codons 5' to the authentic initiation codon, suggesting that cells can regulate translational start sites in these mRNAs. Abrogation of translational control may be a general mechanism of proto-oncogene activation in malignancy. PMID- 3347255 TI - Congress keen to top NIH's requests. PMID- 3347256 TI - NIH gearing up to tackle the human genome. PMID- 3347257 TI - Embargoes on science? PMID- 3347258 TI - Legislation on vitamin D patent makes waves. PMID- 3347259 TI - Pharmaceutical companies profit from Japan's blood boom. PMID- 3347260 TI - AIDS workers going for computer link. PMID- 3347261 TI - Exotic cows born from Indian surrogates. PMID- 3347262 TI - New strategy sought for UK postgraduate medical research. PMID- 3347263 TI - AIDS agreement. PMID- 3347265 TI - India and the United States agree on vaccine programme. PMID- 3347264 TI - Hope for collaboration--brain meets mind in the midwest. PMID- 3347266 TI - CNRS strengthens links with industry. PMID- 3347267 TI - An ethical dilemma. PMID- 3347268 TI - Wet and dry deposition of Chernobyl releases. AB - The passage of the Chernobyl plume over the United Kingdom in May 1986 led to the deposition of radionuclides on the ground by wet and dry deposition processes. Here we analyse rainfall during the passage of the plume and the published monitoring data obtained afterwards, and show that levels of deposited 137Cs can be closely related to rainfall intercepting the plume. 137Cs was present in the atmosphere mostly as particulate species with wet deposition mechanisms dominating. In contrast, 131I was present as particulate and vapour phase material, and reported levels on grass and in cow's milk show that both wet and dry deposition mechanisms were important. 131I on grass and in cow's milk therefore shows a different geographic pattern to 137Cs, and is not so closely related to rainfall. We have calculated washout factors for locations where there are data on deposition, rainfall and air concentrations during the passage of the Chernobyl plume. From these factors and interpolated concentrations in the atmosphere, the total deposition of 137Cs has been estimated at each of 4,000 rain gauge stations in the United Kingdom. The results are presented as deposition contours and have been compared with measurements in parts of the country. Estimates of the total deposition of 131I and 137Cs show that less than or equal to 1% of the estimated total releases from Chernobyl were deposited on the United Kingdom. PMID- 3347269 TI - Phylogenetic trees support the coevolution of parasites and their hosts. AB - The close correspondence often observed between the taxonomy of parasites and their hosts has led to Fahrenholz's rule, which postulates that parasites and their hosts speciate in synchrony. This leads to the prediction that phylogenetic trees of parasites and their hosts should be topologically identical. We report here a test of this prediction which involves the construction of phylogenetic trees for rodents and their ectoparasites using protein electrophoretic data. We find a high degree of concordance in the branching patterns of the trees which suggests that there is a history of cospeciation in this host-parasite assemblage. In several cases where the branching patterns were identical in the host and parasite phylogenies, the branch lengths were also very similar which, given the assumptions of molecular clock theory, strongly suggests that the speciation of these hosts and ectoparasites was roughly contemporaneous and causally related. PMID- 3347270 TI - pH-sensitive activation of the intracellular-pH regulation system in squid axons by ATP-gamma-S. AB - The regulation of intracellular pH (pHi) is essential for normal cell function, and controlled changes in pHi may play a central role in cell activation. Sodium dependent Cl-HCO3 exchange is the dominant mechanism of pHi regulation in the invertebrate cells examined, and also occurs in mammalian cells. The transporter extrudes acid from the cell by exchanging extracellular Na+ and HCO3- (ref. 9) (or a related species) for intracellular Cl- (refs 3, 4). It is blocked by the stilbene derivatives DIDS (4,4'-diisothiocyano-stilbene-2,2'-disulphonate, ref. 10) and SITS (4-acetamido-4'-isothiocyano-stilbene-2,2'-disulphonate, ref. 3), and has a stoichiometry of two intracellular H+ neutralized for each Na+ taken up and each Cl- extruded by the axon. Because the inwardly-directed Na+ concentration gradient is sufficiently large to energize both the HCO3- influx and Cl- efflux, this electroneutral exchanger could be a classic secondary active transporter, thermodynamically independent of ATP hydrolysis. However, at least in the squid axon, the exchanger has an absolute requirement for ATP (ref. 3). Thus, a major unresolved issue is whether this Na-dependent Cl-HCO3 exchanger stoichiometrically hydrolyses ATP (the pump hypothesis), or whether ATP activates the transporter by a mechanism such as phosphorylation or simple binding (the activation hypothesis). We have now explored the role of ATP in pHi regulation by dialysing axons with the ATP analogue ATP-gamma-S. In many systems, ATP-gamma-S is an acceptable substrate for protein kinases, whereas the resulting thiophosphorylated proteins are not as readily hydrolysed by phosphatases as are phosphorylated proteins. Our results rule out the pump hypothesis, and show that the basis of the axon's ATP requirement is the pH-dependent activation (by, for instance, phosphorylation or ATP binding) of the exchanger itself, or of an essential activator. PMID- 3347271 TI - Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA. AB - Tandem-repetitive minisatellite regions in vertebrate DNA frequently show substantial allelic variation in the number of repeat units. This variation is thought to arise through processes such as unequal crossover or replication slippage. We show here that the spontaneous mutation rate to new length alleles at extremely variable human minisatellites is sufficiently high to be directly measurable in human pedigrees. The mutation rate at different loci increases with variability in accord with the neutral mutation/random drift hypothesis, and rises to 5% per gamete for the most unstable human minisatellite isolated. Mutations are sporadic, occur with similar frequencies in sperm and oocytes, and can involve the gain or loss of substantial numbers of repeat units, consistent with length changes arising primarily by unequal exchange at meiosis. Germline instability must therefore be taken into account when using hypervariable loci as genetic markers, particularly in pedigree analysis and parenthood testing. PMID- 3347272 TI - The iscom antigen-presenting system. AB - The immunostimulating complex, or iscom, provides an effective means of presenting antigens to the immune system. Vaccines for influenza, hepatitis B and AIDS are in the offing. PMID- 3347273 TI - Certified nurse-midwives and physicians: perinatal care charges. PMID- 3347274 TI - Full disclosure. PMID- 3347275 TI - Capturing lost charges. PMID- 3347276 TI - Retention: what's it all about? PMID- 3347277 TI - [Epileptic insults leading to neurosurgical intervention]. PMID- 3347278 TI - [Antimicrobial drugs in bronchopulmonary infections]. PMID- 3347280 TI - [Nutrition and sports]. PMID- 3347281 TI - [Runners and those who collapse: hyperthermia in a moderate climate]. PMID- 3347279 TI - [Recombinant human erythropoietin]. PMID- 3347282 TI - [Running in high temperatures]. PMID- 3347283 TI - [Electrocardiography and the family physician, a source of concern?]. PMID- 3347284 TI - [Masked symptoms of acute abdomen during continuous ambulatory peritoneal dialysis]. PMID- 3347285 TI - [Steindler's flexor plasty in paralysis of the elbow flexors]. PMID- 3347286 TI - [The treatment of fingertip injuries using silver sulfadiazine]. PMID- 3347288 TI - [Tuberculostatic agents]. PMID- 3347289 TI - [Munchausen syndrome]. PMID- 3347287 TI - [A patient with acute secretory diarrhea caused by an autochthonous infection with Vibrio parahaemolyticus]. PMID- 3347290 TI - [Resistance against genetic counseling]. PMID- 3347291 TI - [Gastroesophageal reflux in mentally retarded children, a late diagnosis]. PMID- 3347292 TI - [Hemopoietic agents]. PMID- 3347293 TI - [From the mouth of children one hears the truth?]. PMID- 3347294 TI - [The use of auditory brain stem potentials in the neonatal intensive care unit]. PMID- 3347295 TI - [The effect of inhalation treatment with corticosteroids and beta sympathicomimetics on bronchial responsiveness in children]. PMID- 3347296 TI - [Fecal soiling: a painful problem]. PMID- 3347297 TI - [Periodic examination of patients with diabetes mellitus]. PMID- 3347298 TI - [Smoking and pregnancy, a neglected health problem]. PMID- 3347299 TI - [Probability of survival of newborn infants after a pregnancy of less than 26 weeks]. PMID- 3347300 TI - [Hematuria without proteinuria in childhood]. PMID- 3347301 TI - [Chemonucleolysis or surgery in lumbar nucleus pulposus hernia?]. PMID- 3347302 TI - [Alport's syndrome]. PMID- 3347303 TI - [One blood pressure tourniquet for everyone: a recommendation]. PMID- 3347304 TI - [Connective tissue tumors in children]. PMID- 3347305 TI - [Repeat abortion, an accidental event or a disease?]. PMID- 3347306 TI - [Acupuncture as a cure; facts and perspectives]. PMID- 3347307 TI - [Is AIDS an occupational disease for the (para)medical professions?]. PMID- 3347308 TI - [Maintain an open mind about chronic psychiatric patients with a hidden diagnosis]. PMID- 3347309 TI - [Micro-diets in obesity]. PMID- 3347310 TI - [Staphylococcus aureus resistant to methicillin]. PMID- 3347311 TI - [Esophageal spasm as a cause of retrosternal pain, diagnosed by means of 24-hour ambulatory manometry]. PMID- 3347312 TI - [Fractures of the proximal part of the femur in children and adolescents]. PMID- 3347313 TI - [Chinese pills still contaminated]. PMID- 3347314 TI - [Effect of existing eye disorders on occupational practice and leisure activities; epidemiology and prevention of accidents]. PMID- 3347315 TI - [Caroli disease limited to a single liver lobe]. PMID- 3347316 TI - [The nutritive value of meals provided in Dutch hospitals]. PMID- 3347317 TI - [Is there something wrong with bicycling?]. PMID- 3347318 TI - [Hemodynamic complications in the use of bone cement]. PMID- 3347319 TI - Intercondylar fracture of the humerus in an elderly patient--treatment with extension block splintage. PMID- 3347320 TI - Painful hip prosthesis. PMID- 3347321 TI - Gallstone obstruction of the duodenum bulb. PMID- 3347322 TI - Patterns of injury during motor vehicle accidents. PMID- 3347323 TI - Bromocriptine does not accelerate skeletal maturation of tall boys. PMID- 3347324 TI - Extreme adenomatous hyperplasia of Brunner's glands in the proximal jejunum. PMID- 3347325 TI - Metoprolol and hydrochlorothiazide in the treatment of elderly hypertensive patients. A Dutch multicentre trial. The Dutch Investigators Group for the Study of Antihypertensive Treatment in the Elderly. PMID- 3347326 TI - Treatment of malignant non-Hodgkin's lymphoma in elderly patients. PMID- 3347327 TI - The serum concentrations of T3, T4 and TSH in evaluating replacement therapy in primary hypothyroidism. PMID- 3347329 TI - Severe congestive heart failure and clotting abnormalities after lumbar disc surgery. PMID- 3347328 TI - Hypothalamic syndrome due to macroprolactinoma; regression with bromocriptine treatment. PMID- 3347330 TI - Treatment of severe lesions of the lower cervical spine (C3-C7). A clinical study and technical considerations in 102 cases. AB - The authors report 102 cases of severe lesions of the lower cervical spine, in which operation was mandatory. The characteristics of these fractures are discussed, together with the different operative procedures. Posterior osteosynthesis using Roy-Camille's plates was preferred. PMID- 3347331 TI - Characteristic oscillations of intracranial pressure after delayed lowering of blood pressure in patient with shearing injury. AB - A comatose patient with severe shearing injury showed hyperthermia, leucocytosis and decerebration. Rapid disappearance of brain swelling as well as a transient fall of blood pressure were peculiar in his clinical course. Large pressure waves appeared more frequently after such attacks. The authors concluded that cerebral vasomotor instability was caused by a primary lesion throughout an area from the anterior hypothalamus to the upper brain stem. Pre-existing hypoxia in such primary lesions was augmented by hypotensive episodes. Frequent appearance of large pressure waves was thought to represent progressive vascular engorgement followed by an uncontrollable increase of the ICP. PMID- 3347332 TI - Symptomatic Rathke's cleft cysts; clinical and therapeutic data. AB - The authors report on a case of symptomatic Rathke's Cleft Cyst (RCC). The only clinical feature was headache. The cystic fluid was aspirated through a trans sphenoidal approach. The postoperative course was uneventful. The rarity of symptomatic RCC (70 cases described in the literature; 30 operated patients) makes necessary the comparison of all data quoted in the different publications so as to define an appropriate attitude to treatment. It thus seems that the surgical procedure should be limited to an aspiration of the cyst contents through a trans-sphenoidal approach; such a procedure is more reliable than a craniotomy to avoid leakage of the cystic fluid into the subarachnoid space and possible postoperative aseptic meningitis. Some authors discussed the possibility of postoperative radiotherapy although only six patients developed recurrence of their clinical features several years after operation and also the efficacy of such a procedure has not been proved. PMID- 3347333 TI - The effects of acupuncture on the sensory evoked potential response. PMID- 3347334 TI - Arachnoid cysts: unusual aspects and management. AB - Several unusual aspects of primary cerebral arachnoid cysts are presented. The optimal management of these lesions is discussed. Attempts at craniotomy and excision of these cysts is not always effective in eliminating the lesion and may provoke intracranial catastrophies. Huge and bilateral cysts are best treated by cystoperitoneal shunting. In general shunting may be preferable to craniotomy and resection of the cyst. An anti-siphon device is recommended to avoid overdrainage of cerebrospinal fluid. PMID- 3347335 TI - Postoperative cervical pseudomeningocele. AB - A case of postoperative cervical pseudomeningocele in a woman submitted to laminectomy for protruded disc is reported. The patient was investigated by myelography and metrizamide computed tomography and surgically treated with a good neurological result. The other eight reported cases of postoperative cervical pseudomeningocele are reviewed and the role of metrizamide CT scan in diagnosing this unusual complication of cervical laminectomies is emphasized. PMID- 3347336 TI - Frontal encephalocele and the nasal cavity. AB - Congenital encephaloceles are rare lesions which are often present at the occipital region. Occasionally, they are encountered anteriorly where they may erode through the base of the skull or through a congenital defect in it and appear as a nasal polyp. We describe a case of an anterior basal encephalocele which presented with hypertelorism and was mistaken for a nasal polyp. PMID- 3347337 TI - Neurologic disease in biopsy-proven giant cell (temporal) arteritis. AB - Neurologic findings were studied in 166 consecutive patients with biopsy-proven giant cell (temporal) arteritis. Neurologic problems occurred in 51 patients (31%): neuropathies (23), TIA/strokes (12), neuro-otologic syndromes (11), tremor (6), neuropsychiatric syndromes (5), tongue numbness (3), and myelopathy (1). Neuro-ophthalmologic problems occurred in 35 patients (21%): amaurosis fugax (AF) (17), permanent vision loss (PVL) (14), scintillating scotoma (8), and diplopia (3). Abnormalities in large arteries in 52 patients (31%) included bruits and diminished pulses. The carotid artery was involved in 31 patients (bilateral in 58%). Overall, 35% of patients with carotid disease had TIA/stroke, AF, or PVL. PMID- 3347338 TI - The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases. AB - Neuropathologic confirmation is required to validate the NINCDS-ADRDA Work Group criteria for the clinical diagnosis of Alzheimer's disease (AD). Neuropathologic inclusion and exclusion criteria for AD, however, are not uniform. The purpose of this investigation was to examine the confirmation rate for the Work Group criteria against differing neuropathologic criteria for AD. The sample consisted of 57 cases, 22 of which had received a clinical diagnosis of AD. Nine neuropathologic criteria for AD were applied in a blind fashion to each of the 57 cases. Our results indicated that, depending on the neuropathologic criteria applied, the clinicopathologic agreement ranged from 64% to 86%. These findings demonstrate the need for universally accepted neuropathologic and clinical criteria for AD. PMID- 3347339 TI - Autoimmunity in multiple sclerosis. AB - Multiple sclerosis reportedly coexists with disorders of autoimmune origin. The prevalence with which such disorders occur in the MS population has not been adequately investigated. We reviewed the medical records of 828 patients with definite MS and found that 4.8% had a past or present associated disorder in which autoimmune mechanisms presumably play a role. The cumulative prevalence of these disorders was no higher than that estimated for the general population. Serum from 105 patients, without clinical evidence of an associated autoimmune disorder, was tested for the presence of antinuclear, thyroid, parietal cell, smooth muscle, and mitochondrial antibodies. A significantly higher prevalence (p less than 0.01) of generally low titers of one or more autoantibodies was found in serum from the MS group, compared with a control group of 105 patients with other neurologic disorders. The increased frequency of serum autoantibodies probably reflects the existence of a nonspecific B cell overactivity in MS. PMID- 3347340 TI - Magnetic resonance imaging in central nervous system sarcoidosis. AB - We performed brain MRIs on 21 patients with CNS sarcoidosis. Brain CTs were performed in 18 of these. Parenchymal lesions were seen in 17 of 21 with MRI, compared with 9 of 18 with CT. MRI detected a greater number of parenchymal lesions in cases where both CT and MRI were positive, and some lesions appeared more extensive with MRI than with CT. The most common MRI pattern was one of periventricular and multifocal white matter lesions (14 cases). Such a pattern is not specific, and other recognized causes for it were identified in four cases. It is likely, however, that sarcoid tissue causes this pattern in some cases, and confirmation was obtained from cerebral biopsy in one. In six patients, the white matter changes were indistinguishable from those seen in multiple sclerosis. Contrast-enhanced CT in two patients showed diffuse meningeal involvement not seen with MRI. MRI is the investigation of choice in detecting parenchymal changes in the brain of patients with CNS sarcoidosis and may prove useful in monitoring treatment in such cases. PMID- 3347341 TI - Incidence of multiple sclerosis in the town of Sassari, Sardinia, 1965 to 1985: evidence for increasing occurrence of the disease. AB - Prevalence studies carried out in Sardinia from 1975 suggest an increasing occurrence of MS. However, it is questionable whether this increase represents a real change in MS incidence or simply reflects longer survival. Data from 79 patients indicated the average annual incidence for the period 1965 through 1985 was 3.4 per 100,000. On December 31, 1985, the prevalence rate was 69 per 100,000. Evaluation of MS temporal trends showed a significant increase in MS incidence during the study period: values ranged around two per 100,000 in the triennial periods 1965-1967, 1968-1970, and 1971-1973, and around five in each triennium from 1977 onward. PMID- 3347342 TI - Motor dominance and lateral asymmetry of the globus pallidus. AB - Animal experiments suggest that neurochemical and anatomic asymmetries exist within the basal ganglia, particularly the globus pallidus, and that these asymmetries correlate with both preferred direction of rotation and limb preference in lever pressing. Human neurotransmitter studies have also revealed a significant asymmetry within the globus pallidus, the left containing greater amounts of dopamine and choline acetyltransferase than the right. Recent anatomic studies of human subcortical regions, limited to the striatum, have failed to show a size asymmetry. We examined 18 normal brains in subjects ranging in age from 26 weeks gestation to 86 years for volumetric asymmetry of the globus pallidus. We found a significant asymmetry, the left side measuring larger in 16 of 18 brains. Considering the role of the basal ganglia in motor control, this data may reflect a structural basis of either axial or limb motor dominance in humans. PMID- 3347343 TI - Outcome from coma after cardiopulmonary resuscitation: relation to seizures and myoclonus. AB - We studied the effect of seizures and myoclonus following cardiopulmonary resuscitation (CPR) on the outcome of all comatose adult survivors of CPR over an 8-year period. Either seizures or myoclonus occurred in 50 of 114 patients (44%): seizures in 41 patients (36%) and myoclonus in 40 (35%). Status epilepticus or status myoclonus occurred in 36 patients (32%), and 19 (17%) had myoclonic status epilepticus (MSE). Seizures and myoclonus per se were not significantly related to outcome, but status epilepticus, status myoclonus, and, particularly, MSE were predictive of poor outcome as judged by survival and recovery of consciousness. PMID- 3347344 TI - Use of composite scores (megascores) to measure deficit in amyotrophic lateral sclerosis. AB - The Tufts Quantitative Neuromuscular Exam (TQNE) consists of 28 items that were designed to measure voluntary motor deficit in amyotrophic lateral sclerosis (ALS) and related diseases. Individual raw data were converted to Z scores for standardization and then grouped into five megascores with statistical and clinical relevance. The derived megascores were Mega 1, pulmonary function; Mega 2, bulbar function; Mega 3, timed hand activities; Mega 4, isometric arm strength; and Mega 5, isometric leg strength. Megascores should enhance the usefulness of testing in therapeutic trials and in analyzing the natural history of ALS and related diseases. PMID- 3347346 TI - Meningeal carcinomatosis: origin of local IgG production in the CSF. AB - We found that eight of 22 patients with meningeal carcinomatosis from different primary tumors produced local IgG in the CSF, as indicated by elevated IgG index and/or oligoclonal IgG subfractions. Local IgG production, when present, appears in an early stage of the leptomeningeal manifestation and remains detectable over extended observation periods. In autopsied cases with local IgG production, we observed numerous perivascular round-cell infiltrates containing plasma cells and large lymphocytes within the leptomeningeal tumor tissue. After incubation with immunoperoxidase, only these cells showed IgG-specific staining, indicating the site of local IgG production. PMID- 3347347 TI - Geographic distribution of MS in New Zealand: evidence from hospital admissions and deaths. AB - We studied the occurrence of multiple sclerosis (MS) in residents of all regions of New Zealand by analyzing first hospital admissions and deaths. Maoris had a much lower proportion of first admissions and deaths than the proportion of Maoris in the general population. For non-Maoris, both first hospital admission and mortality rates increased steadily from the northern part of the country to the south, with one possible exception. PMID- 3347345 TI - The natural history of motoneuron loss in amyotrophic lateral sclerosis. AB - Using a quantitative, reliable, sensitive and valid measurement technique, we analyzed the rate and pattern of motor deterioration in 50 strictly defined ALS patients for up to 67 months. We observed that the rate of motoneuron loss was linear and symmetric. Bulbar function deteriorated more slowly than respiratory, arm, and leg function. The loss of leg strength was slower than in the arm. No correlation was observed between age at onset and rate of deterioration, or with different regions of onset. Arm strength changed more slowly in women, but other functions showed no male-female differences. These data should prove useful in the design of clinical trials and in generating testable hypotheses of the etiology of this disease. PMID- 3347348 TI - Clomiphene therapy in epileptic women with menstrual disorders. AB - We studied the effects of clomiphene therapy on seizure frequency in 12 women who had clinical and EEG features of complex partial seizures as well as menstrual disorders with reproductive endocrine abnormalities. Ten of the 12 women improved (p less than 0.05); all ten developed normal cycles. The two women who did not improve continued to have irregular prolonged cycles. Average monthly seizure frequency for the entire group declined by 87% (p less than 0.01). Both complex partial and secondary generalized seizures decreased. During the investigation, one unwanted pregnancy occurred, two women developed severe abdominal pain with ultrasound-documented ovarian cysts, and three experienced breast tenderness and pelvic cramps. PMID- 3347349 TI - Studies on the etiology and pathogenesis of motor neuron diseases. II. Clinical and electrophysiologic features of pyramidal dysfunction in macaques fed Lathyrus sativus and IDPN. AB - A primate model of lathyrism has been produced in well-nourished male cynomolgus monkeys chronically fed a fortified diet composed of Lathyrus sativus (chickling or grass pea) and given daily per os an alcoholic extract of this legume. Animals given a diet of non-neurotoxic Cicer arietinum (chick pea) cross-matched with the nutritional properties of the experimental diet served as controls. Another group of animals received the same diet and oral doses of beta, beta' iminodipropionitrile (IDPN), a reference compound that has been termed an "experimental neurolathyrogen." Monkeys fed Lathyrus developed clinical and electrophysiologic evidence of corticospinal deficits after 3 to 10 months of feeding. Animals administered IDPN showed clinical and/or electrophysiologic changes in the PNS and CNS motor and sensory pathways, and signs of cerebellar dysfunction. Since the two primate disorders are separable on clinical and electrophysiologic grounds, further use of the term "experimental neurolathyrogen" to describe the neurotoxic properties of IDPN seems inappropriate. These findings demonstrate the feasibility of developing a model of early human lathyrism in adequately nourished nonhuman primates. PMID- 3347350 TI - Demyelination and decreased S-adenosylmethionine in 5,10 methylenetetrahydrofolate reductase deficiency. AB - We previously described demyelination in the brain and subacute combined degeneration of the spinal cord in a patient with 5,10-methylenetetrahydrofolate reductase deficiency. To assess the role of methionine, S-adenosylmethionine, folate, and neurotransmitter amine metabolism in the demyelination process, we measured these metabolites in CSF from this patient; the findings are compared with those obtained from three patients in whom neurologic deterioration had been halted by the administration of betaine. Folate concentrations were low, and amine and biopterin metabolism were abnormal in all patients. Methionine and S adenosylmethionine concentrations were undetectable in the first patient. In those receiving betaine, methionine concentrations were proportional to the dose administered and S-adenosylmethionine concentrations were near normal. The results provide the first evidence for an association between defective S adenosylmethionine metabolism and demyelination in humans. PMID- 3347351 TI - Chronic progressive sensory ataxic neuropathy with polyclonal gammopathy and disseminated focal perivascular cellular infiltrations. AB - One autopsied case of chronic progressive sensory-ataxic neuropathy with polyclonal elevation of serum and CSF IgG and IgA and without malignancy is reported. A marked loss of large myelinated fibers was universal in both the central and peripheral rami of primary sensory neurons. Fiber loss showed a multifocal patchy pattern in the proximal nerve trunks. The posterior root ganglion cell bodies were moderately atrophic and loss of large cells was observed. Unmyelinated axons were well preserved. The ventral spinal roots, ventral spinal horn cells, and muscles showed minimal involvement. There were focal perivascular mononuclear inflammatory cells without necrotizing vasculitis around the endoneurial and epineurial vessels. Similar perivascular cellular invasions were observed in the visceral organs, occasionally forming germinal follicle centers. This case suggested that this neuropathy has a unique background with a possible immune-mediated basis. PMID- 3347352 TI - Free cytoplasmic Ca++ at rest and after cholinergic stimulus is increased in cultured muscle cells from Duchenne muscular dystrophy patients. AB - We used a fluorescent dye, quin 2, to measure intracellular free calcium ([Ca++]i) in cultured skeletal muscle cells and skin fibroblasts from five Duchenne muscular dystrophy (DMD) patients and from five controls. We observed an enhanced [Ca++]i level, at rest and after acetylcholine (ACh) stimulation, in DMD muscle cells, but we did not detect any difference between DMD and normal skin fibroblasts. The abnormally higher [Ca++]i transient induced by ACh suggests that it plays a critical role in muscle degeneration. The skin fibroblast results suggests that there is no generalized membrane defect. PMID- 3347353 TI - Neuro-ophthalmologic complications of cardiac catheterization. AB - We examined ten patients who, from 1981 to 1986, sustained neuro-ophthalmologic events during cardiac catheterization. Eight patients, most of whom recovered, were believed to have sustained embolic phenomena. Two patients experienced a typical migraine during the catheterization and likewise did well. We conclude that the likelihood of sustaining a neuro-ophthalmic complication during cardiac catheterization is low and that the prognosis after having sustained such a complication is generally favorable. Evidence suggests that artery-to-artery emboli is the dominant pathogenic factor. PMID- 3347354 TI - CT and MRI in maple syrup urine disease. AB - We describe a patient with a variant form of maple syrup urine disease who had unusual CT and MRI features that raised the suspicion of a metabolic disease. There were low density and abnormal signal in the white matter and pallida. Sponginess in these areas is the likely explanation for these findings. PMID- 3347356 TI - Case-control study of completed ischemic stroke in the Parsis of Bombay: a population-based study. AB - All eligible adult cases of completed ischemic stroke (N = 112) derived from a prevalence survey of the Parsi community in Bombay, India, served as the basis of a case-control study of risk factors. The stroke morbidity rate in this group was similar to that reported for North America. A control subject free of stroke was selected randomly from the same population and matched to each case by age and sex. Information was obtained on various risk factors. Hypertension, both by history (odds ratio = 10.8) and by examination (odds ratio = 2.1), had a statistically significant association with stroke (p less than 0.01). This is one of the first community-based case-control studies of stroke in a large developing country. PMID- 3347355 TI - Unusual presentation of cis-platinum neuropathy. AB - Symptoms and signs of cis-diamminedichloroplatinum II (DDP) neuropathy usually develop during treatment and stabilize or improve when DDP is stopped. We report three patients whose symptoms began 3 to 8 weeks after the last dose of DDP and progressed over 1 or 2 months to moderate-marked disability. The clinical picture in each was consistent with DDP neuropathy, and no other cause could be identified. Two of the patients improved over 8 and 27 months to become asymptomatic; the other died 2 months after presentation. It is important to recognize that DDP neuropathy can present after treatment has been discontinued since the clinical picture mimics the paraneoplastic dorsal root ganglionitis, which has a different prognosis. PMID- 3347357 TI - Establishment of a CSF bank. AB - A bank of well-characterized CSF has been established by collecting and storing ( 70 degrees C) CSF samples remaining after completion of routine clinical studies. Over 1,700 individual patient samples were collected during a 12-month period. A database derived largely from information down-loaded from existing hospital based systems includes the results of individual CSF laboratory studies, in addition to the patient age, primary diagnoses, and details of any malignancy. CSF control material is used to verify storage conditions. The CSF bank supplies investigators with CSF handled in a standardized manner for more precise investigation of CNS disease. PMID- 3347359 TI - Spontaneous remission of paraneoplastic ocular flutter and saccadic intrusions. AB - We report two women with ocular flutter and saccadic intrusions, documented by electro-oculography, who had complete spontaneous remission of their ocular motor findings prior to the appearance of a primary neoplastic process remote from the nervous system. Transient elevation of blood HVA and VMA levels was detected in one patient who subsequently had breast cancer. These cases indicate that spontaneous remission of saccadic oscillations does not necessarily imply a benign outcome. Patients with this ocular motor abnormality should be followed closely for signs of a remote neoplasm even if initial investigation is negative. PMID- 3347358 TI - Transient global amnesia and thalamic infarction. AB - We describe the clinical and neuroradiologic features of a patient with two episodes of transient amnesia who later developed persistent amnesia and an acute infarction in the left thalamus. The neurobehavioral manifestations were strikingly similar in all three episodes. Cranial computed tomography was normal following the first two episodes. Thalamic ischemia could explain some cases of transient global amnesia. PMID- 3347360 TI - Varicella optic neuritis. AB - A 14-year-old girl developed severe bilateral optic neuritis 1 week after the onset of chickenpox. Though previous case reports state that complete recovery is the rule, this child had a persistent decrease in visual acuity in the right eye and loss of color vision and defects in visual fields in both eyes. PMID- 3347362 TI - Hyperhidrosis and hypothermia responsive to oxybutynin. PMID- 3347363 TI - Hemidystonia due to subdural hematoma. PMID- 3347364 TI - Paraneoplastic sensory neuronopathy, revisited. PMID- 3347361 TI - Reverse ocular dipping. PMID- 3347365 TI - Imaging studies and EEG in childhood degenerations. PMID- 3347366 TI - Familial amyloidotic neuropathy. PMID- 3347367 TI - Systemic administration of naloxone produces analgesia in BALB/c mice in the formalin pain test. AB - Systemic administration of naloxone usually produces either hyperalgesia or no change in nociception depending on the animal species used and/or the pain test employed. This study, however, demonstrates that naloxone produces a dose dependent analgesia in the formalin pain test using an inbred strain of albino mouse. Female BALB/c, C57BL/6 and CD1 mice were injected subcutaneously with naloxone HCl in saline (0.1 10.0 mg/kg) or saline alone, and tested for analgesia using the formalin test. Naloxone produced a statistically significant dose dependent analgesia in the BALB/c mice, with an ED50 of 0.24 mg/kg and almost total analgesia at doses of 1 mg/kg or greater. No changes in pain behaviour were observed in the C57BL/6 or CD1 strains of mice. We believe this to be the first report of analgesia following administration of doses of naloxone normally used for opioid antagonism. To determine if this effect was specific to the formalin test, the 3 strains of mice were injected subcutaneously with naloxone HCl and tested in the tail-flick test. Naloxone had no analgesic action in this test in any of the strains. PMID- 3347368 TI - Some blood vessels in the rat median eminence are surrounded by a dense plexus of vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI) immunoreactive nerves. AB - Using immunohistochemistry at the light and electron microscopic level some blood vessels along the median eminence were shown to be surrounded by dense networks of vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI) positive fibers. VIP and PHI released from these fibers may contribute to the elevated levels of these two peptides measured in portal blood as compared to peripheral blood by radioimmunoassay. VIP and PHI may also be important in the control of blood flow through the median eminence. PMID- 3347369 TI - The development of primary afferents to the lumbar spinal cord in Xenopus laevis. AB - The development of dorsal root ganglia (DRG) and the primary afferent system of the hindlimb was studied during metamorphosis in Xenopus laevis larvae. The first DRG cells appeared at stage 40 and at stage 48 the first primary afferent fibers entered the lumbar spinal cord where they bifurcated into ascending and descending branches. Primary afferent fibers and the dendrites of the secondary motoneurons contacted first in a lateral (state 56) and later (stage 58) in a dorsomedial terminal field. Reflexogenic hindlimb behaviour at stage 56 concurred with the presence of the lateral terminal field and many unipolar dorsal root ganglion cells. PMID- 3347370 TI - The piriform cortex is not a direct olfactory relay to the mediodorsal thalamic nucleus in cats and rabbits. AB - Following injections of horseradish peroxidase into the mediodorsal thalamic nucleus (MD), retrogradely labeled cells were found in various areas in the cat and rabbit. Among these, olfactory-related areas to which the olfactory bulb projects directly or indirectly via the piriform cortex were the olfactory tubercle, amygdala and insular cortex, while no labeled cells were detected in the piriform cortex and endopiriform nucleus in both species. These results indicate that the piriform cortex and endopiriform nucleus do not send their axons directly to the MD. PMID- 3347372 TI - Response of brown adipose tissue to electrical stimulation of hypothalamic centres in intact and adrenalectomized Zucker rats. AB - Electrical stimulation of the ventromedial nucleus of the hypothalamus (VMN) increased brown adipose tissue (BAT) temperature in lean and obese Zucker rats, whereas stimulation of the paraventricular nucleus (PVN) was without effect in either genotype, before or after adrenalectomy. The prolonged duration of the increase in BAT temperature in the obese (fa/fa) rat observed after VMN stimulation was normalized after adrenalectomy. PMID- 3347371 TI - Neural inputs from the uterus to the paraventricular magnocellular neurons in the rat. AB - Extracellular action potentials were recorded from antidromically identified, tonically firing cells in the hypothalamic paraventricular nucleus (PVN) of ovariectomized, estrogen-treated female rats under urethane anesthesia. Genital or somatic sensory stimuli, or electrical stimulation of the nerves innervating the pelvis were applied. Uterine horn or vaginal distension each excited 33% of the neurons tested. Probing of the cervix had no effect. Hindpaw pinch produced excitation in 39% and inhibition in 11% of the neurons tested. Non-noxious somatic stimuli had no effect. Stimulation of the uterine afferent nerves, the hypogastric and pelvic nerves, excited 55% and 30% of the neurons tested, respectively. Stimulation of a somatic nerve of the hindleg, the sciatic nerve, activated 80% of the neurons tested. These results indicate that specific sensory afferents arrive at the PVN from the uterus; in addition, somatic afferents converge in this hypothalamic nucleus. PMID- 3347373 TI - Spinal cord injury or spinal anesthesia eliminates seizures in myelin-deficient rats. AB - The generalized tonic seizures that occur in myelin-deficient rats can be eliminated temporarily by spinal cord injury or spinal anesthesia. These observations imply that the seizures in this mutant can be triggered by activity in the spinal cord. The results are consistent with an earlier proposal that axons in myelin-deficient CNS fiber tracts can interact to produce abnormal excitation. PMID- 3347374 TI - Observations on choline acetyltransferase containing structures in the CD-1 mouse brain. AB - Central cholinergic structures within the CD-1 mouse were evaluated by immunohistochemical visualization of choline acetyltransferase (ChAT) using the monoclonal antibody AB8. Rostrally, cholinergic neurons were seen within the neostriatum, medial septal nucleus (Ch1), ventral (Ch2) and horizontal (Ch3) limb nuclei and nucleus basalis-substantia innominata complex (Ch4). Caudally, cholinergic neurons were seen in the cuneiformis-pedunculopontine nuclei (Ch5), lateral dorsal tegmental (Ch6) and parabigeminal (Ch8) nuclei as well as the medial habenular nucleus and cranial motor nuclei. Additional cholinergic perikarya were found in the hippocampus and cerebral cortex. ChAT stained fibers were observed in the cerebral cortex and in many fiber fascicles. PMID- 3347376 TI - A specific antiserum recognizes clonidine-displacing substance: implications for the structure of the brain's own clonidine. AB - A polyclonal antiserum was raised in rabbit against the clonidine analog p aminoclonidine (PAC) coupled to hemocyanin. The antiserum (anti-PAC3) exhibited high affinity for unconjugated [3H]PAC (Kd 0.32 +/- 0.07 nM) in a rapid filtration radioimmunoassay. Competition experiments showed that PAC, clonidine, and naphazoline cross-reacted with the anti-PAC3 antiserum, whereas a number of other structurally related compounds did not. An endogenous clonidine-displacing substance (CDS) partially purified from bovine brain also inhibited specific [3H]PAC binding to anti-PAC3 in a dose-dependent manner. Thus, (a) anti-PAC3 antiserum is specific for clonidine and closely related compounds, and (b) CDS may structurally resemble clonidine since it is recognized by this highly specific antiserum. PMID- 3347375 TI - On the relation between seizures and brain lesions after intracerebroventricular kainic acid. AB - To analyze the relation between kainic acid-induced limbic seizures and the associated brain lesions, various doses of kainic acid (117-940 pmol) were administered intracerebroventricularly to unanesthetized rats. Rats which experienced status epilepticus developed lesions in several limbic, neocortical and thalamic regions. However, rats which experienced only temporally discrete seizures (less than 30 min each) suffered neuronal degeneration exclusively in the CA3-CA4 area ipsilateral to the kainic acid infusion, even when other regions exhibited the same total electrographic seizure duration. These results can best be explained by postulating that, in addition to evoking seizures, kainic acid also enhances the toxic effects of seizures on CA3-CA4 neurons. PMID- 3347377 TI - Statistics: friend or foe? PMID- 3347378 TI - Nursing research: what it costs and who will pay. PMID- 3347379 TI - Leadership: theory lets clinical instructors guide students toward autonomy. PMID- 3347380 TI - Fitting RN students into a traditional program: secrets for success. PMID- 3347381 TI - The diagnosis dilemma: one preferred remedy. PMID- 3347382 TI - Community health and home health nursing: keeping the concepts clear. PMID- 3347383 TI - Learning to fight Nicotiana tabacum. PMID- 3347384 TI - Side effects of nicotine dependence. PMID- 3347385 TI - Smoking cessation in primary care settings. PMID- 3347386 TI - Tobacco dependence in treating alcoholism. PMID- 3347388 TI - Clean air at work: it makes sense. PMID- 3347387 TI - The nurse's role: decreasing tobacco use. PMID- 3347389 TI - Scientific basis for workplace clean air. PMID- 3347390 TI - The smoke-free hospital. PMID- 3347391 TI - The joy of smoking. PMID- 3347392 TI - Preventing tobacco dependence. The New Jersey Commission on Smoking or Health. PMID- 3347393 TI - Court decisions. Right to die cases; physician liable for another physician? PMID- 3347394 TI - The role of health professionals. PMID- 3347395 TI - Nutrition and aging. The twelfth Marabou Symposium. PMID- 3347396 TI - Patient classification systems: strategies for the 1990s. PMID- 3347398 TI - SHARE program: a boost to morale. PMID- 3347397 TI - The effect of primary care nursing and feelings of isolation/depersonalization of the critical care nurse: Part I--Background for the study. PMID- 3347399 TI - Proposing a child care center for your hospital. PMID- 3347400 TI - Head nurse education vs. staff nurse turnover: report of a formal study. PMID- 3347401 TI - Nurses and murder charges. PMID- 3347403 TI - Management's responsibility to deal effectively with the risk of HIV exposure for healthcare workers. PMID- 3347404 TI - Beyond fear: the next step in nursing the person with AIDS. PMID- 3347402 TI - Competition vs. cooperation among nurses. PMID- 3347405 TI - Knowledge nurses need to participate on a design team. PMID- 3347406 TI - Primary practice partners (a nurse extender system). PMID- 3347407 TI - A respiratory resource program designed today for tomorrow. PMID- 3347408 TI - The clinical nurse specialist: evaluation issues. PMID- 3347409 TI - The objectives of performance appraisal--or "where can we go from here"? PMID- 3347410 TI - When you don't develop your own: validation methods for patient classification systems. PMID- 3347411 TI - Public health nursing and productivity measurements: are home visit numbers the right focus? PMID- 3347412 TI - Selective first-trimester termination in octuplet and quadruplet pregnancies: clinical and ethical issues. AB - The induction of grand multiple gestations is a known complication of infertility treatments. The obstetric outcome in such cases has been very poor. We have evaluated, counseled, and performed first-trimester selective terminations for four patients, all treated with human menopausal gonadotropin, one with octuplets and three with quadruplets. In all cases, the gestations were reduced to twins. In two of the four cases, the pregnancy continued to near term without problem and resulted in the delivery of healthy twins. In the third case, pregnancy continued without problems for eight weeks, at which time renal agenesis was identified in one of the twins. In the fourth case, preterm labor five weeks later could not be stopped. Significant ethical issues must be addressed. We argue that selective termination in appropriate circumstances (eg, when the ability to carry the pregnancy to viability is very small) is ethically justified because it meets the criterion of least harm and most potential good. PMID- 3347413 TI - Blood or urine measurement of human chorionic gonadotropin for detection of ectopic pregnancy? A comparative study of quantitative and qualitative methods in both fluids. AB - One hundred seventy-five patients with features of ectopic pregnancy were studied, of whom 95 were subsequently shown to have an ectopic pregnancy. Paired blood and urine samples were assayed for human chorionic gonadotropin (hCG) by two radioimmunoassays, one immunoradiometric assay for intact hCG and an immunoradiometric assay for free beta subunit that also detects the "beta core" of hCG in urine. Qualitative testing was also performed using the Tandem Icon method of immunoconcentration on a membrane. The quantitative results for intact hCG showed an approximately unitary relationship between concentrations in both fluids, with a close correlation (r = 0.84, gradient = 1.01). The qualitative tests for hCG in both serum and urine were positive in all patients with ectopic pregnancy. The Tandem Icon is equally useful in blood and urine, whereas quantitative assays are more reliable in the blood. Quantitation of urinary hCG is not recommended because of the variable dilution of the glycoprotein in this fluid. PMID- 3347414 TI - Evaluation and management of the pelvic mass: a review of 540 cases. AB - The management of 540 patients with the diagnoses of "pelvic mass/uterine leiomyomata" was reviewed with respect to preoperative evaluation, surgical procedures, and final pathologic diagnosis. Approximately 6170 patients were admitted to the Gynecology Service at St. Luke's-Roosevelt Hospital Center from July 1984 to June 1985. During this period, 36 of 432 diagnostic laparoscopies (8.3%) and 503 of 1666 laparotomies (30.2%) were performed to evaluate or treat these women. The final diagnoses in the 249 patients admitted with the impression of leiomyomata were: leiomyomata, 235 (94.4%); benign adnexal masses, seven (2.8%); cancers, four (1.6%); and miscellaneous, three (1.2%). Of the 291 patients evaluated for pelvic mass, the findings were: benign ovarian or tubal cysts, 98 (33.7%); leiomyomata, 42 (14.4%); cancers, 40 (13.7%); benign cystic teratomas, 38 (13.1%); endometriosis, 28 (9.6%); miscellaneous, 23 (7.9%); and pelvic inflammatory disease, 22 (7.6%). Correlation between the patient's age, preoperative impression, and final diagnosis is presented with particular attention to the 44 patients (8.1%) in whom malignancy was found. All the possibilities that such masses may represent must be considered preoperatively, and the patient be informed of her risk of malignancy. PMID- 3347415 TI - Management of stage II endometrial adenocarcinoma. AB - Charts of 36 patients with clinical stage II endometrial adenocarcinoma over ten years were reviewed. All were staged before any treatment, in accordance with International Federation of Gynecology and Obstetrics (FIGO) guidelines. Although details of treatment varied, two main protocols were used. Fourteen patients were treated with the "standard" protocol involving external whole-pelvis radiation, followed by intracavitary cesium and then hysterectomy. In 1981, a "modified" protocol was introduced, which called for a hysterectomy immediately following intrauterine and vaginal cesium. External radiation therapy was given only to those patients found to have deep myometrial invasion or cervical involvement. Of 14 patients treated by this protocol, seven had no surgical indication for postoperative external radiation. There was no increase in recurrence in these patients, and the five-year survival rate was 76% for patients treated with the modified protocol compared with 65% for those who had standard therapy. Morbidity related to external radiation therapy occurred in two patients with the standard protocol and one patient who received pelvic radiation on the modified protocol. PMID- 3347416 TI - Toxicity of abdominopelvic radiation in advanced ovarian carcinoma patients after cisplatin/cyclophosphamide therapy and second-look laparotomy. AB - Twenty-seven advanced ovarian carcinoma patients who had received six courses of cyclophosphamide/cisplatin and had either microscopic disease (15 patients) or no pathologically detectable disease (12 patients) after second-look laparotomy were treated with abdominopelvic radiation (2250 cGy to the abdomen and pelvis and a 2250-cGy pelvic boost). Acute myelosuppression or gastrointestinal toxicity prevented completion of treatment in only three patients. However, bowel obstruction occurred in 13 (48%), ten of whom required surgery. Five of these ten had recurrent tumor, but the other five did not. Subsequently two of the latter five did develop a recurrence, one in the lung and one in the liver. A third patient died as an indirect result of radiation damage to the bowel. Median follow-up duration is 17 months from completion of radiation. So far, 13 (48%) have developed progressive disease: four (33%) of the 12 who had a negative second-look laparotomy and nine (60%) of the 15 who had microscopic disease before radiation. While acute toxicity is tolerable, the incidence of serious chronic bowel toxicity is high. Efforts should be made to alter this therapy in order to decrease the frequency of long-term morbidity. PMID- 3347417 TI - Diagnosis of recurrent gynecologic malignancy with fine-needle aspiration cytology. AB - Between 1980-1985, 177 fine-needle aspirations were performed on 139 patients suspected of having recurrent gynecologic malignancy. Suspected sites of recurrence included a pelvic mass (122), peripheral lymph node (39), and a variety of other locations (16). There were 69 positives, 79 negatives, eight suspicious specimens, and 21 specimens inadequate for interpretation. Excluding suspicious or inadequate specimens, the results of the remaining 148 evaluable aspirations were confirmed by histopathologic correlation (35) or subsequent clinical course (113). Because there were no false positives, the specificity of the technique was 100%. The sensitivity was 68%, with an associated false negative rate of 32%. The predictive value of a positive was 100%; that of a negative was 57%. An analysis of the false-negative results failed to show a correlation with cell type, lesion location, previous radiotherapy, or previous chemotherapy. The complication rate was less than 1%. These data support the conclusion that fine-needle aspiration cytology is a safe, highly specific method for diagnosing recurrent gynecologic malignancy. However, in patients with negative fine-needle aspiration cytology and suspected recurrent disease, it would appear that further evaluation is indicated. PMID- 3347418 TI - Failure to prevent meconium aspiration syndrome. AB - To determine the impact of routine naso-oropharyngeal DeLee and tracheal suction on the prevention of meconium aspiration syndrome, we compared 755 infants with meconium-stained fluid, born during a 12-month period (1983), with a similar group of 742 infants born in a previous year (1975) when these suctioning techniques were not routinely used. Morbidity and mortality data from meconium aspiration syndrome in 103 infants, using combined DeLee and tracheal suction during a five-year period (1979-1983), were also analyzed retrospectively. In spite of a combined DeLee and tracheal approach toward the prevention of meconium aspiration, the rate of meconium aspiration syndrome (2%) was not different in 1975 and 1983. Timing of obstetric DeLee suction (whether before or after delivery of the chest) did not influence the presence of meconium below the vocal cords (37 versus 36%, respectively). Even though significant morbidity remained associated with meconium aspiration in both periods studied, a drastic reduction occurred in neonatal mortality, from 46%, in 1975 to 12.5% in 1983, which was probably aided by major advances in perinatal care and supports routine prophylactic suctioning of meconium at birth. From these findings, we suggest that meconium aspiration syndrome is predominantly an intrauterine event secondary to fetal distress, and that DeLee and tracheal suctioning reduce only its severity. PMID- 3347419 TI - Evaluation of arterial oxygen saturation in pregnant patients and their newborns. AB - Continuous oxygen saturation measurements were obtained in 103 pregnant patients and 96 of their newborns by a pulse oximeter during the peripartum period. The parturients received narcotic sedation; epidural, spinal, or general anesthesia; or no analgesia. Seventy-nine patients had oxygen saturation levels over 90% (mean 97.6%), and 24 had one or more oxygen saturation levels less than or equal to 90% (mean 95.6%, P = .001). For all neonates, the mean oxygen saturation was in the "hypoxic range" at one minute (77.6 +/- 11.48%), five minutes (84.4 +/- 7.64%), and ten minutes (89.4 +/- 6.29%). More desaturation episodes were noted in mothers exposed to a central nervous system depressant (P = .041). When mothers with and without desaturation events were compared, no differences were found for age, parity, race, hematocrit, smoking, hypotensive episodes, or delivery route. More maternal desaturation episodes occurred during transport (P = .0016) and while in the recovery room (P = .0003) than in other study periods. Maternal peripartum desaturation events occurred without adverse neonatal effect when prompt treatment was provided. Neonatal hemoglobin oxygen saturation less than or equal to 90% is commonly found within ten minutes after birth and does not always merit the designation of "hypoxia." PMID- 3347420 TI - Effect of birth order on intraventricular hemorrhage in very low birth weight twins. AB - We evaluated the effect of birth order on the incidence and severity of intraventricular hemorrhage in 29 sets of very low birth weight twins (1500 g or less). Intraventricular hemorrhage occurred in 55% of first-presenting twins and 62% of second-presenting twins. The incidence of minor intraventricular hemorrhage (grades I and II) was 41% for first twins and 52% for second twins, whereas the incidence of major intraventricular hemorrhage (grades III and IV) was 14 and 10%, respectively. None of these differences reached statistical significance. We conclude that birth order does not appear to have a major effect on the incidence or severity of intraventricular hemorrhage in very low birth weight twins. PMID- 3347421 TI - Binding of fluorescent phosphatidylcholine in amniotic fluid. AB - Fetal lung maturity can be predicted by the technique of fluorescence polarization using fluorescent phosphatidylcholine instead of diphenylhexatriene. To further elucidate the mechanism of this assay, we used high-speed centrifugation to isolate amniotic fluid lamellar bodies. Each of 75 amniotic fluid samples was separated into two fractions: a lamellar body pellet and a lamellar body-free supernatant fluid. Amniotic fluid and these fractions were assessed in a fluorescence polarization assay using a fluorescent phosphatidylcholine. Regardless of the maturity of the fetal lung, the lamellar body fractions had low polarization values (0.127-0.216), whereas the lamellar body-free fractions had high polarization values (0.266-0.344). Compared with the polarization of amniotic fluid, the fluorescence intensity of the lamellar body fractions had a strong inverse correlation (r = -0.871). The polarization of lamellar body pellets was not linearly related to the polarization of amniotic fluids. These findings do not support the theory that this fluorescence polarization assay measures the microviscosity of surfactant lipids. Instead, we propose that this assay indicates the quantity of surfactant relative to the quantity of nonsurfactant receptors of fluorescent phosphatidylcholine in amniotic fluid. PMID- 3347422 TI - Perinatal regionalization as measured by antenatal referral. AB - To assess the degree of perinatal regionalization, maternal and infant records were reviewed for all very low birth weight (501-1500 g) infants born in calendar years 1985-1986 to residents of the primarily rural North Central Perinatal Region of Illinois. Seventy-one percent of mothers who were expected to deliver in non-center hospitals could have realistically been referred to perinatal centers for delivery. Ninety-four percent of realistic antenatal referrals actually occurred. In Peoria, 79% of mothers expected to deliver very low birth weight infants at non-center hospitals could realistically have been referred to the center for delivery, and all such referrals actually occurred. Because a goal of regionalization is to deliver certain high-risk women in centers, the fact that 94% of rural and 100% of urban realistic antenatal referrals actually occurred suggests that the North Central Perinatal Region is well regionalized. Other centers should study the site of delivery of this or other well-defined regional cohorts of high-risk pregnancies to quantitate how well perinatal care is regionalized in their respective areas. PMID- 3347423 TI - Outcome of trial of labor in patients with a single previous low transverse cesarean section for dystocia. AB - The purpose of this prospective investigation was to evaluate the outcome of trial of labor in women with a history of a single low transverse cesarean section for dystocia in comparison with the outcome in women with a history of cesarean delivery for a reason other than dystocia. During the study period, 89 of 131 patients (68%) with a history of dystocia had a successful trial of labor, compared with 78 of 96 women (81%) who had cesarean delivery for a reason other than dystocia (P less than .025). Within the former group, 79% of women who originally had surgery while still in the latent phase of labor had a successful trial of labor, compared with 61% (.05 less than P less than .10) of patients who had an arrest of dilation in the active phase of labor and 65% (not significant) of those who had an arrest of descent. The only serious complication among study patients was a single instance of uterine scar dehiscence (0.5%). We conclude that approximately two-thirds of patients with a previous cesarean delivery for dystocia will have a successful trial of labor. Of these women, those individuals whose initial operation was performed in the latent phase of labor appear to have the best prognosis for subsequent vaginal delivery. PMID- 3347424 TI - Cesarean section-related maternal mortality in Massachusetts, 1954-1985. AB - We analyzed the data of the Maternal Mortality Committee of the Massachusetts Medical Society to investigate cesarean section-associated maternal deaths. Between 1954-1985, the number of cesarean section-related deaths per 100,000 live births did not significantly change despite a quadrupling of the cesarean section rate. Between 1976-1984, there were 649,375 births and 121,217 cesarean sections in the state. Seven deaths were directly related to cesarean section, a rate of 5.8 per 100,000 cesarean sections. In contrast, the rate for vaginal deliveries was 10.8 per 100,000 vaginal deliveries. We conclude that the risk of maternal death from cesarean section is low. PMID- 3347425 TI - Risk factors for Erb-Duchenne palsy. AB - The risk factors associated with the occurrence of Erb-Duchenne palsy were examined. Of 22 palsies, 18 were noted among 32,088 nondiabetic gravidas (0.56 per 1000) compared with four among 380 diabetic gravidas (10.5 per 1000), a statistically significant difference. One in six infants of diabetic gravidas who sustained shoulder dystocia experienced an Erb-Duchenne palsy. The incidence of precipitate second-stage labors was high (31.8%) among those infants who experienced the neurologic complication. This labor abnormality is not preventable and may contribute, in many ways, to the neurologic complication. Although recently graduated (less than four years' postresidency training) obstetricians, especially if placed in a high-volume practice, were more likely to experience this adverse outcome than more experienced physicians, even the most senior clinicians delivered infants who were affected. PMID- 3347427 TI - Here comes the judge! PMID- 3347426 TI - Methadone maintenance in pregnancy: consequences to care and outcome. AB - A retrospective analysis was conducted on the outcomes of the pregnancies of 26 narcotic-addicted women who were enrolled in a methadone maintenance program. Of these women, 88% continued to use other drugs during their pregnancy, with opiates the most frequently used, and 56% of these women had urine toxicology screens positive for either heroin, cocaine, or benzodiazepines when they presented in labor. When these women were compared with a similar group of 37 pregnant polydrug users who were not in the methadone maintenance program and who delivered during the same 12-month period, there was no difference in the birth weights or in the infants' one- and five-minute Apgar scores. However, the women in the methadone maintenance program had more prenatal visits, more adequate prenatal care, and less anemia than the non-methadone maintenance program drug users. When these two drug-using groups were compared with a control group of pregnant women who delivered within the same time period, there was a significant difference in the birth weights of these two groups. This raises the question of the effectiveness of methadone maintenance programs in promoting fetal growth and well-being and in reducing polydrug use during pregnancy. PMID- 3347429 TI - Internal podalic version with unruptured membranes for the second twin in transverse lie. AB - Internal podalic version of the second twin in transverse lie has usually been performed after first rupturing the membranes of the second amniotic sac. In a prospective study on internal podalic version with unruptured amniotic membranes, 11 second-born twins in transverse lie were successfully delivered, with good neonatal outcome and without birth injuries. From our experience, it appears that this modified technique, when used within the presented guidelines, offers a reasonable alternative for the safe delivery of the second twin. PMID- 3347428 TI - Early discharge after vaginal hysterectomy. AB - Over eight months, 66 patients seen in the author's private practice were deemed suitable candidates for vaginal hysterectomy; 41 of these chose to participate in a continuing study of the feasibility of early discharge after the operation. The principal indication for surgery in these women, who ranged in age from 24-68 years, was abnormal bleeding. Other procedures performed in addition to vaginal hysterectomy did not, in most patients, interfere with early dismissal from the hospital. With the exception of one woman, all were discharged within 24 hours after surgery. There were no cases of delayed infection, hemorrhage, or other postoperative complications that could be attributed to early hospital dismissal. Most patients were able to return to their normal activities much sooner than the usually expected four to six weeks after surgery. PMID- 3347431 TI - Invasive ovarian endometrioid adenofibroma with omental implants and collision with endometrial adenocarcinoma. AB - A case of endometrioid adenofibroma of the ovary with omental implants, extensive invasion into the wall of the ipsilateral fallopian tube, and collision with an endometrial papillary adenocarcinoma is reported. Fewer than 35 malignant cystadenofibromas and adenofibromas have been reported. In all of these cases, the malignant epithelium was believed to originate from preexisting benign tumors. This case is unusual in that it demonstrated no malignant epithelium beyond that of a borderline tumor, but met the criteria of malignancy because of its invasiveness and metastasis. PMID- 3347430 TI - Long-term follow-up and complications of infants with vulvovaginal embryonal rhabdomyosarcoma treated with surgery, radiation therapy, and chemotherapy. AB - The long-term follow-up is presented of three infants with vulvovaginal rhabdomyosarcoma treated at 10, 11, and 15 months of age by radical surgery, pelvic radiation therapy, and chemotherapy. Two patients developed colonic stricture requiring operative repair. One of these two patients also has urinary incontinence secondary to severe bladder contraction. Pelvic radiation did not significantly affect stature. Lateral transposition of the ovaries at the time of surgery preserved endocrine function in one patient with a normal puberty. The other two patients developed normal secondary sexual characteristics with hormonal replacement therapy. These patients perform well academically and socially. They have adapted 14, 14, and 16.5 years after their therapy. PMID- 3347432 TI - Triplet pregnancy with delivery on three separate days. AB - Obstetric complications of triplet pregnancies may make the delivery of extremely premature infants in these multiple gestations inevitable. To our knowledge, this case represents the first report of triplets delivered on three separate days, 16 days apart, using the technique of delayed interval delivery. One of the infants survived. PMID- 3347433 TI - Occult placental abruption after maternal trauma. AB - Three cases of occult abruption after maternal trauma are presented. In each instance, there was no vaginal bleeding, and abdominal findings were subtle. By maintaining a high index of suspicion and monitoring the fetus continuously, the obstetrician may minimize the fetal complications of placental abruption in traumatized pregnant patients. PMID- 3347434 TI - Angiographic arterial embolization to control hemorrhage in abdominal pregnancy: a case report. AB - A case is described in which heavy postoperative bleeding from the placental bed after removal of the fetus in an abdominal pregnancy was managed by selective arterial embolization of the placental vascular bed. Selective angiographic embolization is a useful tool in both obstetric and gynecologic complications when hemorrhage fails to respond to other modes of therapy. PMID- 3347435 TI - Chronic massive fetomaternal hemorrhage: a case report. AB - We report a case of massive chronic fetomaternal hemorrhage with remarkable fetal compensation. The labor course was complicated by a fetal heart rate pattern showing decreased long- and short-term variability and the eventual development of persistent late decelerations. The fetal scalp blood pH and cord blood pH values were normal. A living male infant was delivered by cesarean section for persistent late decelerations. A Kleihauer-Betke stain on a maternal blood sample was positive at 14.5%, which is equivalent to 700 mL of fetal blood in the maternal circulation. PMID- 3347437 TI - Splenic pregnancy--case report. AB - Primary splenic pregnancy is the rarest form of extrauterine pregnancy. Only six cases have previously been documented, none of which occurred in North America. A case of this rare entity is presented in which a pregnancy was found to arise from the spleen, requiring splenectomy. In addition to the classic signs of a fulminant ruptured ectopic pregnancy, a history of upper abdominal pain was the only distinguishing feature. PMID- 3347436 TI - Perinatal septicemia due to the Bacteroidaceae. AB - Two cases of perinatal septicemia due to the Bacteroidaceae are discussed. In contrast to most cases of perinatal septicemia caused by aerobic bacteria, these cases were not associated with prolonged rupture of the fetal membranes. PMID- 3347438 TI - Vulvovaginal sequelae of Stevens-Johnson syndrome and their management. AB - We describe a woman with Stevens-Johnson syndrome, a life-threatening form of erythema multiforme characterized by bullae formation, extensive mucosal damage, and systemic toxicity, and known to be triggered by various drugs, infections, ingestants, or contactants. Serious complications have been reported in most body systems, including cases of permanent damage to the urogenital tract. Three methods of surgical treatment for severe vaginal complications, depending on the degree of vaginal mucosal damage, are described, including the successful treatment of our patient, who had vaginal adenosis, endometriosis, and severe stenosis from this disease. Methods of therapy are presented for possible prevention of severe vaginal sequelae from Stevens-Johnson syndrome. PMID- 3347439 TI - Fevers in patients undergoing vaginal laser surgery. AB - Three patients undergoing laser surgery of the vagina developed high fevers that later regressed, one of them without treatment. The possible causes and implications of these cases are discussed. PMID- 3347440 TI - Retroperitoneal fibrosis presenting as an abdominopelvic mass. PMID- 3347441 TI - Anaphylaxis in pregnancy. AB - Anaphylaxis is a relatively uncommon event in pregnancy that can have serious implications for both mother and fetus. A case is presented of anaphylaxis to intravenous (IV) ampicillin given during labor, and the pertinent literature is reviewed. Maternal morbidity occurred after the use of IV epinephrine. Fetal outcome was good, presumably as a result of prompt delivery near term. The management of anaphylaxis in pregnancy is reviewed. PMID- 3347442 TI - Sickle cell E hemoglobinopathy and pregnancy. AB - The incidence of E hemoglobinopathies has been increasing in the United States. This is the first known case report of hemoglobin S/E in pregnancy. Management was based on the similarities of the S/E and S/beta-thalassemia hemoglobinopathies, and included partial exchange transfusion. Complications included fetal distress, congenital hydrocephalus, and cleft lip and palate. It appears that S/E and E/beta-thalassemia hemoglobinopathies may entail increased perinatal risks, but that favorable pregnancy outcomes may be anticipated with homozygous hemoglobin E or hemoglobin E trait. PMID- 3347443 TI - Aseptic necrosis of the femoral head during pregnancy. AB - Two patients are presented with rare aseptic osteonecrosis of the femoral head appearing during the last trimester of pregnancy. Both patients suffered from increasing pain in one hip joint, beginning about one month before parturition. Radiographs demonstrated local osteoporotic changes of the femoral head on the painful side. Needle aspiration of the hip joint yielded a scant amount of clear, sterile synovial fluid and gave prompt relief of pain in both cases. The patients' history did not demonstrate any predisposing factors to osteonecrosis other than pregnancy. Treatment comprised omission of weight-bearing on the affected lower extremity for a month or two. The patients had completely recovered one year postpartum, and radiographs were normal. PMID- 3347444 TI - Essential thrombocythemia in pregnancy. AB - A 32-year-old women with essential thrombocythemia and a history of bleeding completed a full-term pregnancy. During pregnancy, the platelet count declined markedly to near-normal levels, but returned to prepregnancy levels within two weeks after delivery. The clinical course was uneventful, except for two brief episodes of vaginal bleeding during the second trimester. Possible etiologic mechanisms for pregnancy-related reduction of platelet levels in thrombocythemia include increased platelet consumption or down-regulation of platelet production by a placental or fetal factor. PMID- 3347445 TI - The benefit of cesarean section in acute myocardial infarction complicated by premature labor. AB - A 42-year-old woman with no known risk factors had an acute myocardial infarction at 32 weeks' gestation and went into premature labor. She required invasive hemodynamic monitoring and inotropic support. Congestive heart failure improved dramatically after cesarean section. During the acute infarction, ventricular dysfunction was out of proportion to the ultimate ventricular damage. The concept of the stunned myocardium is used to explain this finding and to justify early cesarean section. Another complication of her infarction, left ventricular thrombosis, has not previously been described in pregnancy. PMID- 3347447 TI - Federal lab certification begins. PMID- 3347446 TI - Ehlers-Danlos syndrome type III in pregnancy. AB - A case of Ehlers-Danlos syndrome type III in pregnancy is described. During the pregnancy, the patient suffered from increasing joint laxity, requiring prolonged bed rest and traction. Early delivery by cesarean section was ultimately performed to relieve her symptoms. We have been unable to find other reports in the literature regarding Ehlers-Danlos syndrome type III in pregnancy. PMID- 3347448 TI - Suspended scaffolding: proper protection reduces fall injuries. PMID- 3347449 TI - Applications for multiple testing increase as technology advances. PMID- 3347450 TI - Electronic equipment provides accuracy in back injury analysis. PMID- 3347451 TI - Functionally illiterate worker also has 'right to understand'. PMID- 3347452 TI - Respirator certification proposal unnecessary, costly, says ISEA. PMID- 3347453 TI - Deep sclerectomy with Nd:YAG laser trabeculotomy ab interno: two-stage procedure. AB - We performed almost the same procedure as Weber's two-stage Nd:YAG laser trabeculotomy. Our technique, developed without knowledge of Weber's findings, also is composed of two stages. In Stage 1, under conjunctival and thin scleral flaps, the deep (4 x 2 mm) scleral block containing the outer wall of Schlemm's canal is removed. Stage 2, the puncturing of the remaining trabeculum with Q switched Nd:YAG laser, is performed the next day. We evaluated the technique in 16 eyes of 11 patients with medically uncontrolled phakic open-angle glaucoma and one eye of a pseudophakic patient with a Binkhorst 2-loop lens. All eyes had unacceptable intraocular pressures (IOPs), despite maximum tolerated medical therapy, and two 360 degrees argon laser trabeculoplasties. The mean preoperative and final postoperative IOPs were 38.3 +/- 19.1 mm Hg and 16.9 +/- 5.3 mm Hg, respectively. Follow-up time was at least 12 months and the results of a 12-month postoperative period were used in all cases. Final postoperative IOP was less than 21 mm Hg in 12 eyes (70%). The only complication during intraoperative and postoperative periods was extremely slight bleeding from the trabeculum or Schlemm's canal in Stage 2; this bleeding was completely absorbed by the following day. PMID- 3347455 TI - Pseudophakic cystoid macular edema: a revised comparison of the incidence with intracapsular and extracapsular cataract extraction. AB - A previous study by one of the authors found no significant difference in the incidence of cystoid macular edema with an intracapsular cataract extraction and the implantation of an iris-supported posterior chamber optic lens, compared with the incidence of cystoid macular edema with an extracapsular extraction and the implantation of a Shearing lens. To test the validity of that conclusion, the charts of 686 patients operated on by one of the authors were reviewed. It was determined that the incidence of both transient and persistent cystoid macular edema was significantly higher in patients who had an intracapsular cataract extraction. Reasons for the contradictory findings are discussed. PMID- 3347454 TI - Study of prostaglandins and intraocular pressure in rabbits after Nd:YAG laser anterior segment procedures. AB - Radioimmunoassay of rabbit aqueous humor one hour after Nd:YAG laser anterior capsulotomies revealed increased concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha), and thromboxane B2 (TBB2). Coincidental rises in intraocular pressure (IOP) and aqueous humor protein were observed. These changes correlated with the laser power used. Pretreatment with topical 1% prednisolone acetate or 1% indomethacin prior to anterior capsulotomies inhibited the post laser rise in PGF1 alpha and TBB2, but did not eliminate the post laser rise in IOP. Small rises in IOP and the concentrations of aqueous PGF1 alpha, TBB2, and protein were observed after Nd:YAG laser iridectomies. These changes were not affected by prior treatment with 1% topical prednisolone acetate. Although PGF1 alpha and TBB2 are elevated after Nd:YAG laser anterior segment procedures, a causal relationship between post treatment IOP rise and PGF1 alpha or TBB2 release could not be determined. PMID- 3347456 TI - A technique for removal of filariasis of the anterior chamber. AB - We describe a useful technique for removing filaria from the anterior chamber. In the case described, an immature female filaria approximately 15 mm in length was removed from the anterior chamber of a 32-year-old man in western Oregon and identified as a species of Dipetalonema. Features of four cases of filarial infection in the anterior chamber from the same geographic area are described. In three out of four cases, the worms were removed alive without difficulty by means of simple irrigation aspiration system. PMID- 3347457 TI - Astigmatism after strabismus surgery. PMID- 3347458 TI - Lidocaine: an anti-tussive for ophthalmic surgery. AB - Intravenous lidocaine suppresses the cough reflex in patients undergoing local operative procedures. Many anti-tussive agents suppress the cough reflex by suppressing the respiratory center. Intravenous lidocaine produces no respiratory depression in doses that suppress the cough reflex. Intravenous lidocaine should be available during all intraocular surgical procedures so it can be used when indicated. PMID- 3347459 TI - Use of fibrin glue in ocular surgery. AB - Cryoprecipitate and thrombin were used to prevent bleeding and induce permanent conjunctival attachment in ten cases of retinal detachment, 40 cases of extracapsular cataract extraction, and ten cases of strabismus. This method proved to be a good alternative to suturing the conjunctiva in each of the above mentioned surgical procedures, and appears to result in a better and more comfortable postoperative course. PMID- 3347460 TI - A new tubing fixation system for silicone oil injection. PMID- 3347461 TI - Automated water control for water cooled lasers. PMID- 3347462 TI - Retrobulbar versus peribulbar anesthesia. PMID- 3347464 TI - The value of cryoprobe-assisted removal of orbital tumors. AB - Freezing a tumor and using a cryoprobe for removing a noninfiltrative space occupying orbital lesion helps greatly in removal of a tumor. The cryoprobe minimizes the potential problem of tearing the capsule of the tumor, decreases bleeding at the time of removal of an hemangioma, and plays a role in removing tumors, either benign or malignant, after they have been biopsied. It is possible that freezing a tumor decreases the potential spilling of tumor cells into the orbit through the biopsy site and upon the delivery of the tumor itself. PMID- 3347463 TI - Natural history and management of advanced Coats' disease. AB - Thirteen children evaluated in the Oncology Service of Wills Eye Hospital from 1976 through 1986 were found to have advanced unilateral Coats' disease, producing a total bullous exudative retinal detachment. All 13 eyes were blind. Six children were given no treatment for their retinopathy, and four of the six eventually developed painful neovascular glaucoma, necessitating enucleation of the affected eye. The other seven children underwent intraocular infusion, drainage of subretinal fluid, and cryotherapy on one or more occasions. None of these seven eyes has developed painful neovascular glaucoma, and the affected eye remains cosmetically acceptable in all seven children. PMID- 3347465 TI - Digoxin cannot account for the reported association of EKG abnormalities and rhegmatogenous retinal detachment. AB - The prevalence of cardiovascular disease (by EKG criteria) in patients with rhegmatogenous retinal detachments has been reported to be more than four times that found in age-matched controls. Adhesion between the retinal pigment epithelium (RPE) and the photoreceptors is facilitated by RPE transport. Because RPE transport is driven by a Na-K ATPase, it has been suggested that the correlation of EKG abnormalities and retinal detachment may be due to clinical use of digoxin, a Na-K ATPase inhibitor frequently given to patients with cardiovascular disease. The prevalence of EKG abnormalities in 299 consecutive patients with primary retinal detachment is about the same as that reported previously. However, 92% of these patients with EKG abnormalities did not take digoxin. Therefore, clinical use of digoxin cannot account for the reported association of EKG abnormalities and rhegmatogenous retinal detachment. PMID- 3347467 TI - Angle-closure glaucoma with pupillary block mechanism in cicatricial retinopathy of prematurity. AB - A 22-year-old man with mild cicatricial retinopathy of prematurity without retrolental mass developed angle-closure glaucoma following pupillary block mechanism. A large lens and a shallow anterior chamber of the premature eye contributed to this mechanism. PMID- 3347466 TI - Complications of argon laser retinal buckling performed in myopic subjects presenting rhegmatogenous degenerations. AB - Twenty-two eyes of twenty-two patients suffering from retinal peripheral degenerations underwent preventive equatorial buckling with argon laser photocoagulation. The fellow eye was used as control. We evaluated the effects of laser photocoagulation on corneal sensitivity, on accommodation, on pupillary diameter and light reflex. In the postoperative period, up to the 3rd month, results were significant with respect to the control eye. The mechanisms to which the onset of these undesired alterations is due are discussed. PMID- 3347468 TI - Electroretinographic and visual-evoked potential abnormalities in patients with beta-thalassemia major. AB - Various ocular abnormalities have been reported in patients with thalassemia, and have been, for the most part, attributed to the toxic effects of high-dose desferrioxamine (DFO). We have performed an electroretinographic and visual evoked potential (VEP) study in 31 thalassemic patients who had never received high doses of DFO. The abnormalities found were very similar to those reported in early siderosis bulbi and included a b1-wave of significantly higher amplitude at 1 min and at the alpha point. VEPs showed a N1-P1 amplitude significantly greater than in controls. These findings, which were more marked in older patients, point to an important causative role of iron in their genesis. PMID- 3347469 TI - A device for easy slitlamp funduscopy with a +90-diopter lens. AB - We developed a device which places the +90-dptr double aspheric lens in the slitlamp common axis channel at 11 mm further from the microscope focal plane, enabling easy visualization of the human fundus. PMID- 3347470 TI - Spatial brightness contrast sensitivity measured with white, green, red and blue light. AB - Grating contrast sensitivity was measured using different colors and different grating orientations. The contrast sensitivity was highest when measured with green light, a little less when measured with red light, and lowest with blue light. The contrast sensitivity with blue light was relatively low compared with green and red light for high spatial frequencies, and relatively high for low spatial sensitivities. The so-called 'oblique effect' was confirmed in this study, but a difference between horizontal and oblique gratings was only found in spatial frequencies higher than 18 cycles/degree. The present study, carried out on 20 persons, suggests that the inter- and intraindividual components of variance are smallest when measured with green light and vertically oriented gratings. PMID- 3347471 TI - [Sources of error in the performance of the R5 test]. AB - A prospective study examining 48 children (age 3.5-7 years) without any ophthalmological symptoms was comparatively performed using the Rodenstock R5 screening test and free examination of visual acuity, phoria and stereopsis. Besides this retinoscopy, interpupillary distance and inclination to instrument accommodation were determined. Using stereopsis targets 121 and 122, the findings of Marquardt (3- to 4-year-old children incline to prefer certain figures, leading to wrong results) can be confirmed. If the actual interpupillary distance is apart from the instrument eyepiece distance, especially if the child's distance is smaller, esophoria can be simulated. Instrument myopia on the one hand may appear as decrease of visual acuity, on the other hand it can be misinterpreted as esophoria. Being aware of these possible errors, the rate of wrong results (mean 22%) can be reduced, leading to better agreement between both methods. PMID- 3347472 TI - [Possibilities and results in the treatment of infertility]. PMID- 3347473 TI - [Monitoring the effect of beclomethasone nasal spray by rhinothermometry in children with hay fever]. PMID- 3347474 TI - [Clinical observations on IgD myeloma]. PMID- 3347476 TI - [High pressure injection injuries of the hand]. PMID- 3347475 TI - [Screening for hypertension in the town of Csongrad]. PMID- 3347477 TI - [Ventricular tachycardia treated with verapamil]. PMID- 3347478 TI - [Indications for transfusion]. PMID- 3347479 TI - [Correlation between serum levels of steroid sex hormones and bilirubin in the newborn infant]. PMID- 3347480 TI - [Significance of bone scintigraphy in the treatment of prostatic cancer]. PMID- 3347481 TI - [Incidence of spontaneous bacterial peritonitis in chronic liver diseases]. PMID- 3347482 TI - [Screening for X chromatin in newborn girls]. PMID- 3347484 TI - Weighing the pros & cons of the HMO. PMID- 3347483 TI - [Heart disease associated with pheochromocytoma]. PMID- 3347485 TI - The additivity of loudness across critical bands: a conjoint measurement approach. PMID- 3347486 TI - The reconstruction of static visual forms from sparse dotted samples. PMID- 3347487 TI - Neural dynamics of 1-D and 2-D brightness perception: a unified model of classical and recent phenomena. PMID- 3347488 TI - Very short-term visual memory for size and shape. PMID- 3347489 TI - Why are left-right spatial codes easier to form than above-below ones? PMID- 3347490 TI - Auditory pattern perception: the effect of tonal frequency range on the perception of temporal order. PMID- 3347491 TI - NLN testing: products and services for registered nursing programs 1988. PMID- 3347492 TI - Localisation of the endpoints of deletions in the 5' region of the Duchenne gene using a sequence isolated by chromosome jumping. AB - We have used chromosome jumping technology to move from within a large intron sequence in the Duchenne muscular dystrophy (DMD) gene to a region adjacent to exons of the gene. The single copy jump clone, HH1, was used to characterise deletions in patients previously shown to be deleted for DNA markers in the 5' end of the gene. 12 out of 15 such patients have breakpoints which lie between HH1 and the genomic locus J-47. Thus the vast majority of the deletions in these patients have proximal breakpoints in a similar region distal to the 5' end of the gene. HH1 was mapped with respect to the X;1 translocation in a DMD female and was shown to lie at least 80 kb from the starting point of the chromosome jump, HIP25. PMID- 3347493 TI - Modification of ribosomal RNA by ribosome-inactivating proteins from plants. AB - We have surveyed 14 different toxic and nontoxic ribosome-inactivating proteins from plants for the ability to act on the RNA of the eucaryotic 60 S ribosomal subunit. All of these proteins act to introduce a specific modification into 26 28 S RNA which renders the RNA sensitive to cleavage by aniline. Sequence analysis of the 5'-termini of the fragments produced by ricin and saporin following aniline cleavage indicate that both proteins possess identical specificity. Our observations support the conclusion of Endo and Tsurugi (J. Biol. Chem. 262, 8128-8130, 1987) that ricin is a specific N-glycosidase and we have located the site of this cleavage by direct sequence analysis. Our results further suggest that all plant ribosome-inactivating proteins function as specific N-glycosidases with the same specificity. PMID- 3347494 TI - Novobiocin induces positive supercoiling of small plasmids from halophilic archaebacteria in vivo. AB - The halophilic archaebacterium Halobacterium strain GRB harbours a multicopy plasmid of 1.7 kb which is negatively supercoiled. After addition of novobiocin to culture medium all 1.7 kb plasmid molecules become positively supercoiled. Positive supercoiling occurs at the same dose of novobiocin inhibiting the eubacterial DNA gyrase in vitro. Novobiocin also induces positive supercoiling of pHV2, a 6.3 kb plasmid from Halobacterium volcanii. These results indicate the existence of a mechanism producing positive superturns in halobacteria. The 1.7 kb plasmid from Halobacterium GRB could be used to produce high amounts of pure positively supercoiled DNA for biophysical and biochemical studies. PMID- 3347495 TI - An oligopurine sequence bias occurs in eukaryotic viruses. AB - Twenty four DNA and RNA viral nucleotide sequences, comprising over 346 kilobases, have been analyzed for the occurrence of strings of contiguous purine or pyrimidine residues. On average strings greater than or equal to 10 contiguous purines or pyrimidines are found three and a half times more frequently than would be expected for a random distribution of bases. Detailed analysis of the 172 kilobase Epstein-Barr viral sequence shows that the bias in favor of contiguous purine residues increases with the length of the purine string. These findings are similar to those seen for genomic DNA from higher eukaryotes. In contrast no overrepresentation of oligopurine or oligopyrimidine strings is observed in 52 kilobases from eight bacteriophage and E. coli DNA sequences. PMID- 3347496 TI - Synthesis of a thymidine phosphoramidite labelled with 13C at C6: relaxation studies of the loop region in a 13C labelled DNA hairpin. AB - A thymidine phosphoramidite labelled at C6 with 13C has been synthesized, and incorporated into a synthetic oligonucleotide, d(CGCGT*T*GT*T*CGCG), which adopts a hairpin conformation. NMR relaxation measurements indicate that internal motion may be present in the loop region of the oligonucleotide. The relaxation behavior of a the C6 carbon in a model compound, N,N-1,3 dimethylthymine is examined in detail as a function of magnetic field strength to determine relative contributions of various mechanisms to the relaxation. The relaxation behaviour of the labelled carbons in the oligonucleotide is discussed in relation to these measurements. PMID- 3347498 TI - Solid-supported ligation primer. PMID- 3347497 TI - Nucleotide sequence of the LuxC gene and the upstream DNA from the bioluminescent system of Vibrio harveyi. AB - The nucleotide sequence of the luxC gene (1431 bp) and the upstream DNA (1049 bp) of the luminescent bacterium Vibrio harveyi has been determined. The luxC gene can be translated into a polypeptide of 55 kDa in excellent agreement with the molecular mass of the reductase polypeptide required for synthesis of the aldehyde substrate for the bioluminescent reaction. Analyses of codon usage showed a high frequency (1.9%) of the isoleucine codon, AUA, in the luxC gene compared to that found in Escherichia coli genes (0.2%) and its absence in the luxA, B and D genes. The low G/C content of the luxC gene and upstream DNA (38 39%) compared to that found in the other lux genes of V. harveyi (45%) was primarily due to a stretch of 500 nucleotides with only a 24% G/C content, extending from 200 bp inside lux C to 300 bp upstream. Moreover, an open reading frame did not extend for more than 48 codons between the luxC gene and 600 bp upstream at which point a gene transcribed in the opposite direction started. As the lux system in the luminescent bacterium, V. fischeri, contains a regulatory gene immediately upstream of luxC transcribed in the same direction, these results show that the organization and regulation of the lux genes have diverged in different luminescent bacteria. PMID- 3347499 TI - The use of large-fragment DNA polymerase I improves the DNAse dependence of the in situ nick-translation procedure. PMID- 3347500 TI - Adenovirus 2 VA RNAI synthesized in SP6 system. PMID- 3347501 TI - Nucleotide sequence of a larval alpha globin gene from Xenopus tropicalis. PMID- 3347502 TI - A novel and rapid method to generate single stranded DNA probes for genomic footprinting. PMID- 3347503 TI - Strain-dependent variation of intron-exon pairings in a group II intron of Schizosaccharomyces pombe. PMID- 3347504 TI - Slippage of DNA polymerase I during synthesis of ds-cDNA. PMID- 3347505 TI - Solid-phase methods for sequencing nucleic acids. VIII. CCS paper-supported degradation of oligodeoxyribonucleotides containing 2'-deoxytubercidin. PMID- 3347506 TI - Tandem promoter/enhancer units create a versatile regulatory element for the expression of genes in mammalian cells. PMID- 3347507 TI - A one-step procedure for the purification of high molecular weight bacterial chromosomal DNA. PMID- 3347508 TI - An occurrence of a noticeable alternating pyrimidine-purine run in the replication origins of tetracycline-resistance plasmids pNSI and pT181. PMID- 3347510 TI - Nursing practice and the legal presumption of competency. PMID- 3347509 TI - Identification of an X-linked member of the Odc gene family in the mouse. PMID- 3347512 TI - Ignorance, ineptitude, indifference: the roots of the nursing shortage. PMID- 3347511 TI - The National Center for Nursing Research: challenges and initiatives. AB - A number of challenges are evident in developing science to guide nursing practice. The National Center for Nursing Research serves as a focal point for the federal programs to promote the profession's ability to confront and grapple with these challenges successfully. PMID- 3347513 TI - Health for all: nursing's role. PMID- 3347514 TI - Nursing beyond national boundaries: the 21st century. PMID- 3347516 TI - Entering the lunchroom: surviving in academia. The Elay Group. PMID- 3347515 TI - The junior student as peer leader. PMID- 3347518 TI - Gastrointestinal symptoms and bowel patterns across the menstrual cycle in dysmenorrhea. AB - Gastrointestinal (GI) functional indicators and symptoms across the menstrual cycle were examined in three groups of women: dysmenorrheic (n = 15), non-pill taking nondysmenorrheic (n = 10), and nondysmenorrheic taking birth control pills (BCPs) (n = 9). Group assignment was based on the reported presence or absence of moderate to severe menstrual cramps in a GI Health Diary which subjects kept for two menstrual cycles. Stool consistencies and frequencies and GI symptoms were also recorded in this diary. Menstrual cycle phase significantly, p = .03, influenced stool consistencies for the sample as a whole with the loosest stools at menses. Reports of stomach pain were higher, p less than .001, at menses than at other cycle phases in all groups, and nausea, p less than .001, and decreased food intake, p less than .01, were more frequently reported by dysmenorrheic women at menses. More dysmenorrheic women had a history of menses-related GI symptoms. Both cycle phase and group differences were significant, p less than .05, for menstrual distress, with negative affect, pain, behavior changes, and autonomic reactions reported more frequently at menses by dysmenorrheic women. PMID- 3347517 TI - Psychosomatic symptoms in parents 2 years after the death of a child with cancer. AB - Forty-five mothers and 30 fathers, representing 58 families, completed the Symptom Checklist 90-Revised, a measure of current psychological and somatic symptoms, 24 months after the death of a child with cancer. The mean scores from six symptom dimensions (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, and hostility) and a global measure of the depth of symptomatology, the Global Severity Index, were contrasted with those of the nonpatient and psychiatric outpatient norms reported by Derogatis (1983). Two years after the child's death parents showed a symptom profile reflecting significantly greater distress than that reported by nonbereaved, nonpatient adults. The results highlight important distinctions between bereaved parents and psychiatric outpatients. PMID- 3347520 TI - Use of regression diagnostics in nursing studies. PMID- 3347519 TI - Comparisons of cardiac output in supine and lateral positions. AB - Cardiac output was measured by thermodilution in 51 adult postcardiac surgical patients using three positions, supine, right lateral, and left lateral, each with 20 degrees backrest elevation. Measurements were taken 4 to 24 hours (M = 10.58) after surgery. Mean cardiac output was significantly different in the three positions, p = .03. This difference resulted from changes in stroke volume, p = .004, rather than changes in heart rate, p = .12. The largest variation occurred between cardiac outputs measured in the supine position and those measured in the left lateral position. Patients at greatest risk for variations in cardiac output with lateral postural change were those with a cardiac index less than 2.3 L/min/m2, those in whom the time elapsed since surgery was less than 12 hours, and those receiving either vasoactive drugs or mechanical ventilation. These results suggest that nurses need to measure cardiac output using a supine position to control for physiological changes that may occur with lateral postural change. PMID- 3347521 TI - Interviewer training and supervision. PMID- 3347522 TI - Developmental and temperament outcomes of sensory stimulation in healthy infants. AB - Eighty-one healthy, full-term infants were randomly assigned to a control group or one of three experimental conditions: daily administration of a cephalocaudal stroking procedure; placement on a multisensory hammock that provided auditory, vestibular, and tactile stimulation during expected sleep cycles; and a combination of the prior two treatments. All interventions were given during the first 3 months of life. Infants in the control group received the natural stimulation provided in their home environments without additional supplementation. Four- and 8-month assessments were done using the Bayley Scales of Infant Development and the Revised Infant Temperament Questionnaire. There were no significant treatment effects on weight or psychomotor development. Although infants receiving unimodal stimulation obtained lower 8-month cognitive development scores than infants in other experimental and control groups, their scores were within normal range. Control group infants achieved the most optimum mood and distractibility scores at both 4 and 8 months. PMID- 3347523 TI - Return of functional ability after childbirth. AB - Recovery of functional ability after childbirth was examined in a sample of 30 women who had vaginal deliveries and 40 who had cesarean births. Recovery of functional ability after childbirth was defined as the resumption of household, social and community, and occupational activities and assumption of infant care responsibilities. Only 51% of the women reported they had regained their usual level of energy by the end of the 6-week postpartum period; 72% of the vaginally delivered women reported regaining their physical energy within this period, but only 34% of the cesarean delivered women had done so. Differences were also noted between cesarean- and vaginally delivered women in the interval until assumption of infant care responsibilities and resumption of certain household tasks, socializing with friends, and participation in religious organizations. Recovery of functional ability was also found to be affected by maternal and neonatal complications, and their presence was associated with postponed return to employment. Findings suggest that the traditional 6-week recovery period from childbirth needs to be reconsidered, particularly for women experiencing cesarean deliveries or maternal or neonatal postdelivery complications. PMID- 3347524 TI - Postpartal anxiety and depression in mothers of term and preterm infants. AB - This study examined differences in anxiety and depression in mothers of term and preterm infants in the first week postpartum and over the next 6 weeks. Mothers of 41 preterm infants were matched with 41 mothers of term infants on parity, type of delivery, age, and race. Sixteen mothers of preterm infants and 10 mothers of term infants completed all 7 weeks of data collection. Mothers of preterm infants were significantly more anxious and depressed than mothers of term infants in the first postpartal week but this difference did not persist over time. Maternal affect was unrelated to parity or type of delivery in the first postpartal week and over time. There were no differences among mothers of premature infants in initial anxiety or depression, based on the level of illness of the infant. PMID- 3347525 TI - Progression of labor pain in primiparas and multiparas. AB - The purpose of this study was to systematically describe the dimensions of pain during the progression of labor in primiparas and multiparas. Fifty primiparas and 88 multiparas were assessed for pain when the cervix was dilated 2-4 cm, 5-7 cm, and 8-10 cm. The sensory component of in-labor pain was more severe than the affective component for both primiparas and multiparas throughout labor and delivery except during Stage III when primiparas reported more intense affective pain. Primiparas reported more intense sensory pain in Stages I and III and more intense affective pain in all three stages of labor than the multiparas even though they consumed significantly more pain medications than the multiparas. PMID- 3347526 TI - Social support in patients' and husbands' adjustment to breast cancer. AB - Data were obtained from 50 mastectomy patients and their husbands at 3 days and 30 days postsurgery to determine the nature of the relationship between social support and the adjustment of mastectomy patients and their husbands over time. Psychosocial adjustment was related to both patients' and husbands' levels of social support. Patients and husbands who reported higher levels of social support reported fewer adjustment difficulties at both 3 days and 30 days postsurgery. Patients and husbands differed significantly in the levels of support they perceived over time; husbands perceived less support from friends, nurses, and physicians. This study underscores the importance of assessing the support resources of both patients and husbands over time. PMID- 3347527 TI - Finding meaning: antecedents of uncertainty in illness. AB - In this study a portion of the uncertainty in illness model was tested. Antecedents to uncertainty tested were the stimuli frame variables of symptom pattern and event familiarity and the structure provider variables of education, social support, and credible authority. Data were collected on a convenience sample of 61 women with gynecological cancer at the time of major treatment effect. Findings supported the proposed model with an empirically generated revised model presenting the influence of antecedents on specific areas of uncertainty. Divergent paths for reducing uncertainty were found. Social support, credible authority, and event familiarity had the greatest influence on lowering the level of uncertainty. Event familiarity and credible authority were primarily effective in reducing the complexity surrounding treatment and the system of care. Social support functioned to decrease the level of ambiguity concerning the state of the illness. Findings generally support the proposed explantation for uncertainty arousal and have substantive significance in identifying the sources of stimuli leading to uncertainty arousal and modification. PMID- 3347528 TI - The great divide. Interview by Peter Morris. PMID- 3347529 TI - 1,000 fatal errors. PMID- 3347530 TI - Over the limit? PMID- 3347532 TI - On the road. PMID- 3347531 TI - Thatcher's hidden agenda. PMID- 3347534 TI - Understanding partial sight. PMID- 3347533 TI - The patient's world. PMID- 3347535 TI - 'Inherently helpful' people wanted. PMID- 3347536 TI - Facing up to mastectomy. PMID- 3347537 TI - Should doctors control discharge? The case for; the case against. PMID- 3347538 TI - HIV-related dementia. PMID- 3347539 TI - Schizophrenia: the search for therapeutic responses. PMID- 3347540 TI - Dietetics. Cancer cachexia. PMID- 3347541 TI - Measuring care. Evaluation of care: measurement in clinical situations. PMID- 3347542 TI - Hospital speak. PMID- 3347543 TI - The famine that won't go away. Interview by Pamela Holmes. PMID- 3347544 TI - Why are more babies dying? PMID- 3347545 TI - Thrown to the lions. PMID- 3347546 TI - Recruit and retain. Where have all the nurses gone? PMID- 3347547 TI - Recruit and retain. None but the brave. PMID- 3347549 TI - Handle with care--my skin is fragile. PMID- 3347548 TI - Education. Cheers! PMID- 3347550 TI - Coming to terms with mastectomy. PMID- 3347551 TI - The smell of the grease paint. Interview by Laurence Dopson. PMID- 3347552 TI - Who knows best? PMID- 3347553 TI - Held in police custody. PMID- 3347554 TI - Catheters: the acquisition of bacteriuria; emptying urinary drainage bags; meatal cleansing. PMID- 3347555 TI - Measuring care. Why use measurement? Part 2. PMID- 3347556 TI - Walking out. PMID- 3347558 TI - The numbers. PMID- 3347557 TI - Working on. PMID- 3347559 TI - Should nurses strike? The case for; the case against. PMID- 3347560 TI - Do models work? PMID- 3347561 TI - Computer-aided Cumberlege. PMID- 3347562 TI - A day in the life. PMID- 3347563 TI - The unborn patient. PMID- 3347564 TI - Systems of life. No. 156. Senior systems. 21. PMID- 3347565 TI - Recruit and retain. Giving up. PMID- 3347566 TI - Setting up NT assertiveness training groups. PMID- 3347567 TI - Mental health: the journal for psychiatric nurses. PMID- 3347568 TI - Mental health. What will happen to Jane? PMID- 3347569 TI - Mental health. They know better. PMID- 3347570 TI - Mental health. Curse or cure? PMID- 3347571 TI - Measuring care. Budgeting in the National Health Service. Part 3. PMID- 3347572 TI - Alzheimer's disease. PMID- 3347574 TI - Urinary incontinence in the elderly. PMID- 3347573 TI - Alzheimer's disease. A psychiatrist's perspective. AB - Alzheimer's disease is a catastrophic disease for both the patient and family with medical, psychologic, and social ramifications. The psychiatrist can function as the primary clinician, team leader, or consultant in the effort to manage the process of diagnosis and treatment through the months and years of progressive deterioration of the patient. Psychiatrists consult and collaborate with neurologists, internists, and other medical specialists and participate with nurses, social workers, dietitians, and physical therapists in the care of patients with AD and their families. Although the present state of treatment is limited to palliative therapies, basic and clinical psychiatric research is directed at the quest for etiologies and definitive treatments. PMID- 3347575 TI - The nursing costs of urinary incontinence in a nursing home population. AB - The labor resources and costs of caring for incontinence in a nursing home population are explored. Data from a work measurement study have been applied to patient assessment results to estimate the total costs of labor for three states and the U.S. as a whole. Incontinence care costs an estimated $1.1 billion per year in the US; this represents 3 to 4 per cent of all Medicaid payments made to nursing homes. PMID- 3347576 TI - Nursing evaluation and treatment of geriatric outpatients with urinary incontinence. Geriatric day hospital model: a case study. AB - Nurses have ideal skills to detect, assess, and treat urinary incontinence in elderly outpatients. A practical approach to promoting continence is presented. The Geriatric Day Hospital model provides an outpatient alternative for evaluating and treating frail elderly patients with multiple problems, including urinary incontinence. PMID- 3347577 TI - Continence restoration in the homebound patient. AB - The restoration of continence in the homebound client often depends on the nurse's conviction that restoration is possible. In many cases, a thorough assessment of the incontinent client will not only identify the cause of incontinence, but will also present a framework for its treatment. The first step is simply the recognition of the problem and the desire for the nurse to facilitate change. PMID- 3347578 TI - Nursing assessments in the inpatient geriatric population. AB - Thorough assessment is essential in caring for the institutionalized elderly who have difficulty with urine control. The assessment should include a physical examination, a functional assessment, and an evaluation of the environment. The physical examination should be completed in a timely fashion after incontinence develops in order to rule out treatable causes of urine loss. The examination includes a health history and physical examination, with special attention being given to the genitourinary system. A urine specimen should be obtained during the examination to rule out bladder infection. The functional assessment of the patient is one of the most important aspects of the patient assessment. This is particularly true for elderly inpatients because much of the incontinence found in nursing homes is attributable to functional deficits. The functional assessment should address the history of the patient's incontinence, the patient's cognitive abilities and potential for participating in continence care, the patient's mobility, and the patient's abilities related to activities of daily living. Deficits in any of these areas may contribute to or cause urinary incontinence. In addition to the physical examination and functional assessment of the patient, the environment should be evaluated. The visibility, location, and structure of the toileting facilities can serve to either promote or impair urine control. In addition to the physical facilities provided, the overall nursing care approach may foster or hinder the patient's ability to maintain urinary continence. Nursing assessment that addresses these three areas will provide information that is needed to develop a nursing care plan that will maximize the patient's potential for urine control. PMID- 3347579 TI - Nursing management of urinary incontinence in geriatric inpatients. AB - The management and treatment of incontinence represent two interrelated areas- providing enough providers of care and describing the types of management and treatment options available to the incontinent patient. This article has stressed that adequate staffing underlies any successful program of continence management and treatment. In addition, many options for the management and treatment of incontinence in the elderly have been presented. Of importance are the specific nursing implications that will make many continence protocols successful. These guidelines can provide the basis for planning patient care through the nursing process. This article has also addressed management and treatment strategies for incontinence that not only improve incontinence in patients but may cure it. These include behavioral management strategies which nurses should be encouraged to use in treating incontinent patients in the community. These same behavioral management strategies are being studied in inpatient settings, and the results indicate that nurses in inpatient settings and long-term care facilities should implement behavioral treatment programs for incontinent patients. PMID- 3347580 TI - Behavioral management in the inpatient geriatric population. AB - Urinary incontinence is a reversible problem in many nursing home patients. The types of patients that respond to nursing management procedures have been identified in this article. Specific diagnostic and rehabilitative assessments, as well as treatment procedures, have been described in a fashion that makes them usable by most nursing professionals in long-term care facilities. Two key issues remain to be addressed. The foremost issue is that, once patients are taught to request toileting assistance, the challenge remains to motivate staff to render that assistance over long periods of time. Second, a number of patients with urologic conditions (most notably, high residual urine volumes and low bladder capacities) do not respond well to nursing management. The type of medical or nursing treatment best suited for these patients has not yet been resolved. Nevertheless, this article has detailed techniques that positively affect incontinence in nursing home patients. Nursing implementation of prompted voiding can dramatically improve continence within the geriatric inpatient population. PMID- 3347581 TI - Educating nurses to care for the incontinent patient. AB - Urinary incontinence among nursing home patients is a very common problem. Until quite recently, incontinence was believed to be impossible or unnecessary to treat except through the use of absorbent pads and diapers. The cost of this type of management to the facility in terms of laundry, labor, and supplies, as well as to patients' well-being, is very high. Recent data suggest that at least some incontinent nursing home patients can benefit from treatment programs that can be taught to the nurse's aide staff and that, at the very least, will reduce laundry and supply costs. The significance of an improvement in patient morale or a decrease in the incidence of complications resulting from incontinence has yet to be assessed, but should be considered. In addition, even a partially successful treatment program may be helpful to the nurses caring for these patients as the nurses' sense of hopelessness and frustration about managing incontinent patients may be reduced. Finally, an active treatment program for continence, instituted by nurses, advances the nursing care of these patients from custodial nursing care to therapeutic nursing care. PMID- 3347582 TI - Care of the patient with Alzheimer's disease living at home. AB - Although the majority of people with Alzheimer's disease and related disorders are cared for in the home for most of their illness, there are few resources available on a consistent basis for nursing interaction. Nurses employed in a variety of settings provide ongoing information and support for families and caregivers in order to provide well-informed care. Because of the complexity of symptom presentation and care, the use of a simple conceptual model can be a valuable aid, helping families to understand behavioral alterations. The evaluation of behaviors as stress related assists both families and caregivers in determining the cause and effect of activities and environment to assist in enhancing comfort and life quality for both. PMID- 3347583 TI - Community management of Alzheimer's disease. AB - Community-based long-term care for victims of AD requires coordination and creativity on the part of a variety of health care professionals, including nurses, physicians, social workers, ancillary therapists, day-care coordinators, and staff in state and federal agencies, as well as of a variety of nonprofessionals who can provide ongoing home care or community agency assistance. The primary role of the health care professional in the community is to assist family members and care agencies in identifying, assessing, and implementing appropriate care for the person with a dementing illness. Much of that role involves matching family and patient needs with available services and participating in local, state, and federal organizations that project the type and extent of services needed now and in the future. Nursing care ranges from participating at the organizational or planning level to actually implementing hands-on care. PMID- 3347585 TI - Victims of Alzheimer's disease and the environment. AB - The environment plays an essential role in the functioning and care of older persons, particularly those with Alzheimer's disease. This article describes the characteristics of the environment that affect the functioning of persons with Alzheimer's disease and the interaction between the person and environment. Assessment and interventions based on environmental characteristics and person environment interaction are identified. PMID- 3347584 TI - Management of patients with Alzheimer's disease in long-term care facilities. AB - The care of residents with AD in long-term care facilities presents a number of challenges to nursing staff. The institutionalized person with AD displays a number of behaviors that are difficult to manage on traditional, integrated nursing units. In these units, behaviors such as wandering and falling are often managed by chemical and physical restraints. Multiple, complex stimuli, common on integrated units, contribute to the confusion and disorientation experienced by residents with AD. An alternative setting, the special-care unit designed specifically to meet the needs of residents with AD, has been described. Special care units modify the environment of the traditional nursing unit to promote the safety of demented residents. The units are an attempt to reduce or control the amount of sensory stimulation in order to prevent catastrophic behaviors in the residents and maximize patient functioning. Staff on special-care units are selected specifically for their commitment to the unique care demands required by residents with AD. Ordinarily, staff in long-term care settings need specialized education to provide this care. A research project designed to evaluate the effectiveness of a special-care unit was also described. This research is valuable to residents with AD, their families, managers, and policy makers of long-term care institutions concerned with the effective use of resources. Considerable costs are involved in the construction and staffing of special-care units. However, the potential costs and threats to quality of care associated with care of residents with AD on traditional units make it imperative to evaluate the effectiveness of special-care units. With the increasing number of persons expected to develop AD, nurses, managers of long-term care facilities, and policy makers are faced with the difficult prospect of determining the most effective means of caring for these residents. Because there have been no definitive, comprehensive studies of special care units, there is an absence of empiric support for the many proposed advantages. Few studies have used systematic measurement techniques or measures with established reliability and validity. Given the growing number of elderly persons in the United States and the expected growth in the number of nursing home residents with AD, it is important to establish the value of special treatment units for residents with AD. PMID- 3347587 TI - Subcostal cross-sectional echocardiographic imaging of patent ductus arteriosus. AB - A modified subcostal short-axis cross-sectional echocardiographic view for imaging the patent ductus arteriosus (PDA) was studied. A total of 22 newborns with PDA and various associated cardiac anomalies and 16 newborns without PDA were examined. The PDA was imaged in the subcostal view in 19 newborns. In the control group, the absence of the PDA was established in 13 newborns and considered probable in three. The PDA was optimally imaged in the subcostal view in patients with normal or enlarged pulmonary artery, mainly those with the hypoplastic left heart. Among the eight patients with small pulmonary artery (pulmonary atresia or severe tetralogy of Fallot), the PDA was imaged in the subcostal view in three and in the suprasternal view in eight. By combining the suprasternal and the subcostal views, the PDA was imaged in each instance. PMID- 3347586 TI - Myocardial ischemia in Kawasaki disease: follow-up study by cardiac catheterization and coronary angiography. AB - The clinical course of ischemic heart disease due to Kawasaki disease was analyzed. The subjects (children aged two months to eight years) were divided into two groups. Group 1 (n = 23) consisted of children who had sustained myocardial infarction (MI) and group 2 (n = 13) of those without clinical symptoms or signs of MI, but in whom signs of an obstructive lesion had appeared on coronary arteriography during the follow-up period. Changes in the left ventricular ejection fraction (LVEF) and the appearance of coronary arterial lesions on first and second angiography were analyzed in the two groups. It was found that (a) LVEF (51.4 +/- 13.4%, mean +/- SD) at the first study, obtained after MI in group 1, was significantly lower than that (64.3 +/- 3.7%) at the second one in group 2, which revealed recently developed obstructive lesions; (b) there was no significant difference between the two groups as to the severity of stenotic lesions on coronary arteriography; and (c) comparison of LVEF at the first angiography with that at the second study showed significant improvement in group 1 (1st, 54.2 +/- 12.0%; and 2nd, 60.8 +/- 9.7%) and significant depression in group 2 (1st, 68.1 +/- 4.4%; and 2nd, 64.3 +/- 3.7%). PMID- 3347588 TI - Prolapsed valve of the foramen ovale in newborns and infants with coarctation of the aorta. AB - Out of 60 newborns and infants with symptomatic coarctation of the aorta, 34 had a significant left-to-right shunt at atrial level. In 20 of these 34 children, the atrial shunt had disappeared after surgical correction of the coarctation. All patients with this "reversible" shunt, thought to be secondary to an incompetent valve of the foramen ovale, were younger than 35 days at first cardiac catheterization. Left atrial pressure and left atrial volume of these patients did not differ significantly from those in a control group without atrial shunt. The conditions necessary for the development of a valve-incompetent foramen ovale include not only an increased left ventricular work load, but also a thin and pliable valve of the foramen ovale. It is only in infants younger than one month of age that the valve is thin and pliable enough to prolapse through the foramen ovale and form a channel between the two atria, which results in a left-to-right atrial shunt. PMID- 3347590 TI - Unusual ultrasound finding of patent ductus arteriosus in a preterm infant. AB - Patency of the ductus arteriosus (PDA) is a common finding in small premature infants. Recently pulsed-Doppler-cross sectional echocardiography (PD-CSE) has been successfully used in these patients. We report a case of a premature infant with an unusual PD-CSE pattern. PMID- 3347589 TI - Effect on growth of children with cardiac dysrhythmias treated with amiodarone. AB - We report the results of treatment with amiodarone in nine children with dysrhythmias resistant to conventional drugs, namely, one with ventricular tachycardia, two with atrial tachycardia, one with junctional tachycardia, three with reciprocal rhythm tachycardia, and two with Wolff-Parkinson-White syndrome. The initial dose was 800 mg/1.73 m2, administered for two weeks, followed by half the dose for five days a week. The duration of the treatment varied from nine months to 19 months (mean duration, 13 months). Patients were followed up for a period ranging between nine and 33 months (mean period, 17 months). A complete remission was obtained in 56% of patients and partial success in 46%. The following side effects were detected: photosensitization in two; effect on weight, height, growth velocity, and thyroid hormones in three, six, five, and six, respectively; and acceleration in bone age in three. These effects were observed from two to nine months after the beginning of treatment. They persisted for 5-18 months after treatment had been suspended. The main side effect of amiodarone in children is presumably initial hypothyroidism, followed by a biological hyperthyroid reaction. For these reasons we suggest that amiodarone should be restricted as an alternative drug for resistant critical dysrhythmias and be used only for a limited period of two years. PMID- 3347591 TI - Progressive vascular lesions in Williams-Beuren syndrome. AB - We report two patients with Williams-Beuren syndrome. The first patient showed no evidence of coarctation of the aorta at the first examination. Seven years later, she developed coarctation of the aorta. In the second patient, we found the progression of renal artery stenosis by serial angiography. We report that vascular lesions may be progressive in Williams-Beuren syndrome. PMID- 3347593 TI - Atypical ventricular tachycardia and alternating Osborn waves induced by spontaneous mild hypothermia. AB - A one-month-old infant developed atypical ventricular tachycardia, complete right bundle branch black, and alternating 2:1 Osborn waves during spontaneous mild hypothermia; 10 h after rewarming, the electrocardiogram was normal. PMID- 3347592 TI - Myocardial damage after a scorpion sting: long-term echocardiographic follow-up. AB - A seven-year-old girl, stung by a scorpion, was hospitalized in a confused state with signs of myocarditis and pulmonary edema. In spite of clinical improvement within 24 h, 14 serial echocardiograms and electrocardiograms performed during a four-month period showed severe changes. There have been no previously published reports of echocardiographic studies showing myocardial changes after a scorpion sting. PMID- 3347594 TI - Dimensions of cardiac chambers and great vessels by cross-sectional echocardiography in infants and children. AB - A total of 120 healthy infants, children, and teenagers were examined by cross sectional echocardiography. Right and left atrial and ventricular dimensions and areas were measured in the parasternal, apical, and subcostal views. Dimensions of the inferior caval vein, the pulmonary artery and the aorta were obtained in the parasternal, suprasternal, and subcostal views. Reproducibility was studied in separate material consisting of 19 children with various forms of congenital heart disease examined consecutively by two different observers. Interobserver reproducibility was expressed as the 95% tolerance limit for the difference between two measurements. Good correlation with body surface area was demonstrated for all measurements, and the regression equations for the normal values of the parameters studied are given. Interobserver reproducibility was fairly good for measurements in the parasternal views, but moderate or low for measurements in the apical and the subcostal four-chamber views. Measurements in cross-sectional echocardiography are clinically useful, especially in the study of the right-sided cardiac structures that are difficult to evaluate with M-mode echocardiography, but the problems of reproducibility have to be taken into account. PMID- 3347596 TI - Three predominant proteins secreted by the human prostate gland. AB - Analyses of the proteins of azoospermic ejaculates from subjects with defective seminal vesicles demonstrated that three prostatic-secreted proteins were predominant. Prostatic acid phosphatase (PAP), prostate-specific antigen (PSA; or gamma-seminoprotein), and beta-microseminoprotein (beta-MSP; or beta-inhibin), were identified as the three predominant proteins secreted by the normal human prostate gland. Immunohistochemical localization of these proteins, in the epithelium of normal prostatic acini and ducts, with the avidin-biotin complex procedure demonstrated that each PAP-immunoreactive cell was invariably immunoreactive both with PSA-and beta-MSP-monospecific antisera as well. PMID- 3347595 TI - Androgen-independent epithelial cells of the rat ventral prostate. AB - Androgen-independent cell lines have been clonally selected from primary cultures of androgen-dependent epithelial cells from the rat ventral prostate. These rapidly dividing epithelial-like cells (RDE) have altered morphology and adherence characteristics. Unlike normal prostate epithelial cells, the RDE cell lines do not require androgens for cell division or cell survival. In the presence of physiological concentrations of testosterone, the isoelectric focusing patterns of prostatic acid phosphatases are abnormal in these RDE cells, and the prostate steroid-binding protein genes are not expressed. The loss of androgen dependence is not due to the inability of RDE cells to metabolize testosterone to 5 alpha-dihydrotestosterone, the active androgen, since the RDE cell lines metabolize testosterone in a manner similar to normal androgen dependent epithelial cells. When RDE cells are grown on collagen matrices, the cells assume ductlike structures, similar to prostatic acini, although PSBP gene expression is not induced. When seeded into soft agar these cell lines form distinct foci, suggesting that they are potentially tumorigenic. PMID- 3347597 TI - [Development of clinical cytology in Switzerland]. PMID- 3347598 TI - [Aortic amyloid. Pathogenesis and significance]. PMID- 3347600 TI - [Systemic hemangioendothelio(mato)sis]. PMID- 3347599 TI - [Morphology of the parathyroid glands in primary hyperparathyroidism]. PMID- 3347601 TI - [Primary embryonal rhabdomyosarcoma of the liver simulating malignant liver mesenchymoma]. PMID- 3347602 TI - [Williams-Campbell syndrome]. PMID- 3347603 TI - [Fatal course of mesenteric deciduosis in a gravida I]. PMID- 3347604 TI - [Echinococcus cysticus of the thyroid gland]. PMID- 3347605 TI - The differential effects of calcium starvation on Duchenne muscular dystrophy fibroblasts. AB - The effects of nutrient deprivation on normal and Duchenne muscular dystrophy fibroblasts were examined. The requirements for Ca2+ and fetal bovine serum were assessed by their effects on the cells' ability to support viral replication, and by ability of the cells to divide in the presence of low levels of these nutrients. When grown in Ca2+-deficient media, Duchenne fibroblasts supported viral replication at a rate 2- to 2.5-fold greater than did normal fibroblasts. At normal Ca2+ levels, Duchenne fibroblasts supported viral replication at levels slightly lower than their normal counterparts. After 48 hr in medium containing 0.2 mM Ca2+, the growth of normal cells was arrested, while Duchenne fibroblasts were relatively unaffected. When grown in medium containing either 0.2 or 2.0% serum, the growth of normal cells was arrested within 48 hr, with cell death occurring within 72 hr. Duchenne fibroblasts continued to divide at these serum levels for 72 hr, reaching higher cell densities than normal cells. These results suggest that a defect related to Ca2+ metabolism may be part of the Duchenne phenotype, which could be used to identify Duchenne muscular dystrophy cells. PMID- 3347606 TI - Rat metabolic adaptation to ammonia inhalation. AB - Rats exposed to 25 or 300 ppm NH3 vapor for 5-15 days 6 hr daily showed dose dependent blood ammonia after 5 days. Brain and blood glutamine were also increased at the same time in rats exposed to 300 ppm. The blood ammonia concentration of the exposed rats resumed control levels at 10 and 15 days while hepatic citrulline synthesis increased above that of the controls. The animals exposed to 300 ppm NH3 showed initially a slight acidosis. As circulating ammonia decreased, brain and blood glutamine returned to the control range. Our findings support the idea that ureagenesis is aimed mainly at the removal of NH+4 with only secondary and small effects on the acid-base balance. PMID- 3347607 TI - Sexual dimorphism in N-acetyltransferase activity, hydroxyindole-O methyltransferase activity, and melatonin content in the Harderian gland of Syrian hamsters: changes following gonadectomy. AB - The activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) and the melatonin content of the Harderian glands of intact and gonadectomized male and female Syrian hamsters were studied. NAT activity in intact male Harderian glands was twice that of the female. Prepubertal or adult castrated males exhibited a decrease in NAT activity to a level comparable to that seen in the female. Testosterone implants in the castrated males led to a recovery of the original male NAT levels. Intact male hamsters had very low levels of Harderian HIOMT activity and melatonin content in comparison with the glands of the females. Prepubertal gonadectomy but not castration of adult males raised the levels of HIOMT activity and the melatonin content to those of the females. Bilateral ovariectomy had no effect on melatonin content, NAT activity, or HIOMT activity in the female hamster Harderian gland. PMID- 3347608 TI - Day-night differences in the response of the pineal gland to swimming stress. AB - The effect of swimming stress on pineal N-acetyltransferase activity, hydroxyindole-O-methyltransferase (HIOMT) activity, and melatonin content was studied during the day and night in adult male rats. At night, elevated pineal activity was suppressed by light exposure before the animals swam. During the day, swimming for 2 hr did not stimulate NAT activity unless the animals were pretreated with desmethylimipramine (DMI), a norepinephrine uptake blocker. Pineal melatonin content after daytime swimming exhibited a weak rise, unless DMI was injected, in which case melatonin levels showed a highly significant increase. Swimming at night caused a greater (compared to daytime levels) increase in NAT activity in both noninjected and DMI-injected rats. Melatonin levels at night were highly significantly stimulated (compared to daytime values) even without pretreatment of the rats with DMI. The greater response of the rat pineal to swimming stress at night may relate either to an increase in the number of beta-adrenergic receptors in the pinealocyte membrane at night or to a reduced capacity of the sympathetic neurons in the pineal to take up excess circulating catecholamines. Pineal HIOMT activity was not influenced by swimming (with or without DMI) either during the day or at night. PMID- 3347609 TI - Circulating autoantibodies to mammalian tissue kallikreins. AB - Autoantibodies to tissue kallikrein (EC 3.4.21.35) were discovered in normal human, rat, mouse, and guinea pig sera. Three independent methods--binding of iodolabeled antigen, enzyme-linked immunosorbent assay (ELISA), and immunoblotting--were used to demonstrate these kallikrein autoantibodies. Autoantibodies from rat and human sera were purified, using rat and human tissue kallikrein-affinity chromatography, respectively. Purified rat kallikrein autoantibody bound 50% of 125I-labeled rat urinary kallikrein upon incubation of antibody at 2.5 X 10(-10) M. The subtypes of rat and human kallikrein autoantibodies were determined by an ELISA, using antisera to immunoglobulin subclasses. In both species, autoantibody was predominantly IgG (approximately 80%) and some IgM (approximately 20%). Purified autoantibodies from rat and human sera were separated on sodium deodecyl sulfate-polyacrylamide gels, and their subunits were identified by Western blot analyses, using anti-rat and anti-human IgG antibodies, respectively. When primary cultures of mouse spleen cells were incubated for 1 to 5 days with lipopolysaccharide (1 to 5 micrograms/ml), the anti-kallikrein antibodies in the media increased up to seven-fold. We have demonstrated circulating autoantibodies that recognize and bind both autologous and heterologous kallikrein; however, their significance to the function of the tissue kallikrein-kinin system in normal and disease states remains to be explored. PMID- 3347610 TI - Cellular origin of prolonged induction of ornithine decarboxylase in the rat ovary. AB - The temporal changes of ornithine decarboxylase (ODC) activity were investigated in the immature rat ovary following a single subcutaneous injection of pregnant mare serum gonadotropin (PMSG). A dose-response relationship was established. Maximal ODC activity was obtained at a dose of 25 IU of PMSG. This increase in ODC activity was accompanied by an increase of ovarian weight before reaching a maximum. A 250-fold increase of ODC activity was observed 1 day following a single dose of PMSG (50 IU). The enzyme specific activity only returned to the control level 4-5 days after hormone treatment. Immunoreactive ODC in immature, PMSG-primed rat ovaries and in heavily luteinized rat ovaries was localized utilizing the immunoperoxidase method and an antibody to ODC. Immunoreactive enzyme was confined to the cytoplasm of the granulosa cells but was not present in luteal cells. Thecal cells showed only weak immunostaining. This study provides clear evidence that the granulosa cell is the unique source of ODC activity in response to PMSG treatment. Furthermore, these data support the concept that polyamines play a role in granulosa cell proliferation and hence follicular development. PMID- 3347611 TI - Developmental changes in rat thyroid responsiveness to thyrotropin administered by the subcutaneous and peroral route. AB - It has been demonstrated that orally administered thyrotropin (bovine, bTSH) evokes an increase in circulating T4 and T3 levels in 15-day-old suckling rat pups, but not in weaned animals. Because the feedback mechanisms of the hypothalamo-pituitary-thyroid axis change dramatically during the neonatal period, we chose to examine the efficacy of exogenous bTSH in eliciting a thyrostimulatory response via the subcutaneous (sc) or peroral (po) route in rat pups at 5, 8, 12, and 15 days postpartum. Suckling pups were divided into four groups and received one of the following: (i) 2 IU bTSH/100 g body wt administered sc; (ii) distilled H2O (dH2O) sc; (iii) 2 IU bTSH/100 g body wt given po; (iv) dH2O po. Animals were sacrificed at Time 0 and 1, 2, and 3 hr post treatment, and the collected serum was analyzed for T4 and T3 by RIA. Maximum serum T4 levels were attained at 2-3 hr post-treatment, and the T4 response to sc bTSH was significantly greater than that of the po-bTSH groups at all ages examined. This difference became progressively greater with increasing age, due to a persistent decline in T4 responsiveness in animals receiving po-bTSH. No significant differences in T4 or T3 levels attained were observed in 8-day-old rat pups treated with rat vs bovine TSH, either sc or po. Percentage T4 response (vs basal levels) steadily declined between Days 5 and 15 postpartum, in both sc- and po-bTSH treatment groups. Percentage T3 responsiveness to sc-bTSH also declined between 5 and 12 days postpartum, after which time T3 generation increased. Our results suggest that the neonatal rat is highly responsive to exogenous TSH late in the first week of life, and that the permeability of the gut at this stage of development further facilitates the impact of orally ingested TSH in the suckling. PMID- 3347612 TI - Effect of capsaicin pretreatment on capsaicin-induced catecholamine secretion from the adrenal medulla in rats. AB - The effect of capsaicin pretreatment on adrenal catecholamine secretion induced by intravenously administered capsaicin was investigated in alpha-chloralose and urethane anesthetized rats. In neonatal vehicle pretreated rats, capsaicin (200 micrograms/kg, iv) caused a rapid and significant increase in adrenal epinephrine secretion, but neonatal capsaicin pretreatment (50 mg/kg, sc, on the 2nd day of life) significantly reduced both the basal and capsaicin-induced epinephrine secretion from the adrenal medulla. Adult capsaicin pretreatment (6 increasing doses/6 days, total 310 mg/kg, sc) also reduced both the basal and capsaicin stimulated adrenal epinephrine secretion, though it was less effective compared with the neonatal capsaicin pretreatment. These results suggest the participation of capsaicin-sensitive neurons in capsaicin-induced catecholamine secretion from the adrenal medulla. PMID- 3347613 TI - Vitamin D mediated intestinal calcium transport: ultrastructural distribution of calbindin-D28 K following calcitriol. PMID- 3347614 TI - Theophylline inhibits active Ca transport in rat intestine by inhibiting Ca binding by CaBP. PMID- 3347615 TI - Facilitated diffusion of calcium by calcium-binding protein: its role in intestinal calcium absorption. PMID- 3347616 TI - Calcium dissociation from mastoparan complexes of calmodulin and its tryptic fragments measured with Quin 2. PMID- 3347617 TI - Inositol phosphate levels during Ca2+ reloading of internal Ca2+ stores in the exocrine pancreas. PMID- 3347620 TI - Non-saturable Ca transport in the rat intestine is via the paracellular pathway. PMID- 3347621 TI - Paracellular transport of inorganic phosphate into bile in intrahepatic cholestasis. PMID- 3347619 TI - Contributions of cellular and paracellular pathways to transepithelial intestinal calcium transport. AB - The small intestine may supply adequate levels of nutritionally required calcium in the absence of stimulated (1,25(OH)2-D3) cell-mediated mechanism of absorption if dietary calcium levels are sufficiently high. This same route may also account for net loss of systemic calcium due to asymmetrical paracellular calcium secretion in the absence of sufficient dietary calcium. Fine adjustments in net calcium balance may occur in the large intestine where inefficiencies of paracellular leaks are significantly reduced and larger calcium gradients can be sustained. PMID- 3347618 TI - Calcium transport in plasma membrane subfractions of rat liver. AB - The selective demonstration of ATP dependent calcium uptake and calcium dependent phosphorylation of a 135 kD intermediate in isolated basolateral liver plasma membrane vesicles suggest that the basolateral plasma membrane of rat hepatocytes contains an ATP dependent calcium transport system with an apparent molecular weight of 135,000. The failure to demonstrate ATP dependent calcium uptake in simultaneously isolated canalicular plasma membrane vesicles suggests the absence of a similar ATP dependent calcium transport system on the canalicular domain. Additional phosphoproteins of 200 and 110 kD could be assigned to microsomal contamination of the isolated plasma membrane subfractions. A canalicular specific 70 kD phosphorylated intermediate presumably does not represent a Ca++ ATPase. Calcium dependent phosphorylation of the basolateral 135 kD intermediate is maximal at physiologic pH (7.0, 7.5), when the calcium pump is active but not at pH 8.0. The 135 kD phosphoprotein has also been shown for erythrocyte Ca++ ATPase and for kidney basolateral Ca++ ATPase (De Smedt et al., 1984; Niggli et al., 1979). PMID- 3347623 TI - Cooperative effect of thyroid hormones and vitamin D on intestinal calcium and phosphate transport. PMID- 3347622 TI - Multihormonal regulation of the vitamin D-dependent calcium-binding protein gene. PMID- 3347624 TI - Parathyroid hormone reduces phosphate transport irreversibly in a cultured renal cell line, OK. PMID- 3347625 TI - Effect of glucose on calcium transport in rat duodenum. PMID- 3347627 TI - Reduced duodenal enterocyte calcium fluxes, decreased 1,25(OH)2D3 and abnormal brush border membrane in the spontaneously hypertensive rat. PMID- 3347626 TI - Effect of pH on the low and high affinity Na+-phosphate co-transport system in rat renal cortex. PMID- 3347628 TI - Influence of recombinant IGF-I (somatomedin C) on sodium-dependent phosphate transport in cultured renal epithelium. PMID- 3347629 TI - Study of the 1 alpha-hydroxylation of 25-hydroxyvitamin D in phosphate diabetes. PMID- 3347630 TI - Regulation of calcium in tumor cells. PMID- 3347631 TI - Effect of dietary vitamin B-6 deficiency on calcium fluxes in rat enterocytes. PMID- 3347632 TI - Intestinal phosphate transport: localization, properties and identification, a progress report. PMID- 3347633 TI - Phosphate transport adaptation in intestinal brush border membrane vesicles (BBMV) and plasma levels of 1,25-dihydroxycholecalciferol. PMID- 3347634 TI - Phosphate-binding protein isolated from kidney and intestine brush-border membranes. PMID- 3347635 TI - Sodium-independent phosphate transport in brush-border membrane vesicles prepared from the outer medulla of pig kidneys. PMID- 3347636 TI - Modulation of Na/P-cotransport activity in opossum kidney cells by extracellular phosphate. PMID- 3347637 TI - Phosphate and calcium homeostasis in young spontaneously hypertensive rats. PMID- 3347638 TI - [European poisonous snakes and their toxins]. PMID- 3347639 TI - [Changes in the properties of solutions through molecular variations and salt formation]. PMID- 3347640 TI - Sleigh bells ringing: an introduction into medicine. PMID- 3347641 TI - The attending physician and the Holy Grail. PMID- 3347642 TI - Old doctors and old patients. PMID- 3347643 TI - Is DNA God? PMID- 3347644 TI - Physician failure as portrayed in literature: Hilfiker, Arrowsmith, and Lydgate. PMID- 3347645 TI - Ethical dilemmas for physicians in armed conflicts--a panel discussion. PMID- 3347646 TI - On excellence. PMID- 3347647 TI - Medical role models. PMID- 3347648 TI - Academic medical centers. PMID- 3347649 TI - Past and present. Wanted: a new clinical base for medical education. PMID- 3347650 TI - From curiosity to knowledge: the role of the library in medical education. PMID- 3347651 TI - Comparison of cyclic and sustained passive stretching using a mechanical device to increase resting length of hamstring muscles. AB - The purpose of this study was to compare the effects of cyclic versus sustained passive stretching with a mechanical device on resting hamstring muscles' length. Group 1 subjects (5 men, 17 women) underwent cyclic stretching of their right hamstring musculature, and Group 2 subjects (5 men, 16 women) underwent sustained stretching of their right hamstring musculature. The stretching procedures were performed for 15 minutes on 5 consecutive days. A follow-up examination of the subjects' relative knee flexion range of motion was made one week posttreatment. The Group 1 subjects had a mean ROM increase of 15.4 +/- 5.0 degrees after the five stretching treatments and maintained a mean ROM increase of 10.4 +/- 5.5 degrees on the follow-up examination (p less than .001). In Group 2, the five stretching treatments resulted in a mean ROM increase of 13.4 +/- 4.4 degrees, and a mean increase of 7.9 +/- 4.0 degrees was maintained on the follow-up examination (p less than .001). Linear regression analysis revealed that initial ROM, sex, and treatment method significantly contributed to increases in ROM from Day 1 of treatment to the follow-up examination (F = 6.04; df = 4,36; p less than .0008). The cyclic stretching method resulted in a greater gain in ROM when the other variables were considered. Predicted values of ROM increases were also examined and discussed. PMID- 3347652 TI - Reliability of isometric muscle testing of knee flexor and extensor muscles in patients with connective tissue disease. AB - This two-part study evaluated the reliability of inexpensive devices for isometric muscle testing on patients. First, the relationship between gauge readings of the devices and known weights was evaluated. Coefficients of determination and regression lines were used to determine the strength and nature of this relationship, which was determined to be linear. Second, intratester reliability for force measurements of isometric knee extension and flexion motions was determined for 30 patients with connective tissue diseases. Right knee extensor and flexor muscle forces were measured during two sessions. The measurements between sessions were compared for degree of agreement using intraclass correlation coefficients. Intraclass correlation coefficients ranged from .90 to .95 for knee flexor force measurements and from .75 to .85 for knee extensor force measurements. Based on the results of this study, this measuring device can be used reliably to measure knee extensor muscle force at 50 degrees and knee flexor muscle force at 30 and 70 degrees. PMID- 3347653 TI - Electromyographic and dynamometric characteristics of female pelvic-floor musculature. AB - The purpose of this study was to determine whether differences existed on dynamometer recordings of muscle strength and electromyographic activity of the pelvic floor in 5 pregnant and 10 nonpregnant women. Pelvic-floor musculature strength measurements, using a perineometer, showed no significant differences between groups. All subjects could hold maximal voluntary contractions for three seconds, but pelvic-floor strength measurements decreased rapidly beyond three seconds. Integrated electromyographic recordings failed to show significant differences between groups. A periodicity of integrated electromyographic activity was observed in both pregnant and nonpregnant subjects. Great variability in the amount of integrated electromyographic activity was observed among both groups during maximal voluntary contractions. The practice of requesting that individuals with pelvic-floor dysfunction hold maximal voluntary contractions longer than three seconds may not be efficacious. Electromyographic measures must be complemented by strength measures for adequate evaluation and treatment of pelvic-floor dysfunction. PMID- 3347654 TI - Principles of clinical decision making--an introduction to decision analysis. A special communication. AB - Physical therapists are becoming increasingly aware of the growing complexity of clinical decision making. The level of understanding and the sophistication necessary to diagnose, treat, and manage medical problems has increased concomitantly with the increase in new diagnostic and therapeutic procedures. The purposes of this special communication are to discuss the principles of clinical decision making and to present a hypothetical situation to illustrate a decision analysis process for choosing among alternative treatment protocols. PMID- 3347655 TI - Endobronchial drainage of undiagnosed lung abscess during chest physical therapy. A case report. AB - Bronchial drainage, positive-pressure lung inflation, chest-wall percussion, and suctioning were performed in a patient with postoperative atelectasis, lung infection, and respiratory failure. A previously undiagnosed posterior lung abscess subsequently drained into the bronchial tree, causing dissemination of the infection and a severe deterioration of pulmonary function. Dissemination of pulmonary infection from a lung abscess is a possible complication that should be considered when prescribing and administering chest physical therapy. PMID- 3347656 TI - The dinosaur of academic physical therapy. PMID- 3347657 TI - Precision rhinoplasty. Part I: The role of life-size photographs and soft-tissue cephalometric analysis. AB - I describe a simple technique of full-scale life-size photography using marker/stickers and a ruler at the side of the face as an index for magnification. I also report a technique of soft-tissue cephalometric analysis that consists of some new proportion and some old angles and measurements. This technique will enable the plastic surgeon, even if not artistically inclined, to draw an aesthetically pleasing and very proportionate profile outline of the nose and measure the proportions of the front view on the majority of patients. The difference between the patient's nasal outline and the planned nasal definition is then measured and expressed in quarters of millimeters to give the surgeon a very precise numeric guide for surgery. This will help the plastic surgeon define the aesthetic goals very accurately and also might be helpful in detecting other facial disharmonies that might be influential in the outcome of the rhinoplasty. Using this technique of analysis, along with the prediction guidelines extrapolated from my study on soft-tissue response to surgical alteration, one can develop a fairly predictable approach to rhinoplasty. PMID- 3347658 TI - Precision rhinoplasty. Part II: Prediction. AB - This retrospective study was undertaken to investigate the soft-tissue response rate to the skeletal and soft-tissue alterations following a rhinoplasty. Ninety eight patients, 80 females and 18 males, with a mean follow-up of 13 months, were included in this study. The tracings of the outline of preoperative cephaloxerograms and life-size photographs were superimposed on the postoperative ones, and the differences were measured and confirmed with measurements of intraoperative resected segments. The soft-tissue response to skeletal alterations was measured in seven different zones. Zone 1 (nasion) and zone 7 (nasal spine area) had the lowest mean response rate of approximately 25 percent. Zone 2 (proximal bridge) and zone 3 (midbridge) had a 60 percent response rate. Zone 4 (supratip area) had a 43 percent response, zone 5 had a 41 percent response, and zone 6 had a 40 percent response rate. There were statistically significant differences among the response rates of thick, medium, and thin noses. Age was an important factor in zones 1, 4, 5, 6, and 7. The patient's sex did not influence the soft-tissue response rate to skeletal alterations. The soft tissue response in relation to the alar base narrowing was about 52 percent. This study reveals a predictable soft-tissue response to skeletal alterations on all zones except zone 7 (nasal spine area). PMID- 3347659 TI - On rhinomanometry in rhinoplasty. AB - Changes in nasal obstruction, nasal airway resistance, and postoperative nose appearance were evaluated in 92 rhinoplasty patients. Fifty-six patients had a deviation of their nose from the midline preoperatively. They were improved according to rhinomanometry whether the rhinoplasty was combined with a functional septoplasty or with a submucous resection. Among the other 36 patients who did not have a deviation of the nose from the midline, 23 had a rhinoplasty combined with a functional septoplasty and 13 had no surgery on the septum at all. Rhinomanometrically, only patients operated on with the combined operation were improved; the rest became worse, even in terms of nasal obstruction. Among 58 patients from both groups with preoperative nasal obstruction, there was agreement for 76 percent between the subjective and rhinomanometric changes. The advantages of giving the rhinomanometric results in a polar coordinate system are discussed. PMID- 3347660 TI - Treatment of burn alopecia with tissue expanders in children. AB - During the past 18 months, 60 tissue expanders were utilized in the reconstruction of 42 children with burn alopecia of the scalp not amenable to a single excision and primary closure at the Shriners Burns Institute in Galveston, Texas. The children were grouped according to the degree of alopecia. All patients with defects of 15 percent or less of the total hair-bearing scalp were able to obtain complete closure of their defects with two operations, i.e., one to place the expander and the second to remove the expander and advance the flaps. Some patients with defects up to 40 percent were closed with serial expansion. Patients with even larger defects had a significant reduction in the percentage of alopecia and benefited from re-creation of anterior hairlines. We have encountered a postoperative complication rate of 10 percent. When compared to previous methods of treating burn alopecia, tissue expansion allows a more rapid closure, fewer operations and coincident anesthetics, and decreased total length of hospitalization. PMID- 3347661 TI - Quantitative analysis of the thickness of human skin and subcutaneous tissue following controlled expansion with a silicone implant. AB - Histologic quantitation of the thickness of human tissues that were expanded using silicone expanders showed that the epidermis underwent significant thickening after 5 weeks to 5 months of expansion. The dermis and subcutaneous tissue, on the other hand, were significantly thinner after expansion. Capsules were formed in all 19 patients. The capsule was significantly thickest after 2 to 2.5 months of expansion. Expanded tissues 2 years after cessation of expansion had the same thickness as control tissues and had no remnant fibrous capsule. PMID- 3347662 TI - Temporalis fascia grafts for facial and nasal contour augmentation. AB - For the past 70 years, fascial grafts have been used in reconstructive surgery mainly because of their tensile strength. Although the thigh (fasciae latae) has been the principal donor site, fascia taken from the temporalis muscle has the advantages of (1) ease of harvest under local anesthesia, (2) usually being in the same operative field, (3) minimal postoperative discomfort, and (4) negligible residual scar deformity. These grafts can be effectively used as the sole source of contour augmentation of facial depressions in primary as well as secondary rhinoplasty. Such grafts undergo an initial uniform shrinkage (approximately 20 percent) during the first 4 to 6 weeks postoperatively due to compaction and condensation of the fibrous tissue of the fascia, after which the grafts stabilize and become firm. Concavities should be overcorrected accordingly. No inflammation or encapsulation has been seen clinically or histologically in 18 patients followed for periods ranging from 6 to 18 months. PMID- 3347663 TI - Use of the temporoparietal free fascial flap in the upper extremity. AB - Reconstruction of hand coverage has been limited to flaps with the drawbacks of bulkiness and donor-site morbidity. In contrast, the temporoparietal fascia is a thin, pliable, well-vascularized sheet of tissue available in abundant quantity. It leaves an inconspicuous donor site within the hair-bearing scalp. In addition, microvascular transfer is facilitated by the consistent, reliable, and large caliber axial superficial temporal vascular supply. The branches of the superficial temporal system provide flexibility in designing axial-pattern flaps. Secondary reconstructive surgery can be safely performed beneath the flap. The intrinsic vascularity of the flap may be useful in revascularizing scarred or irradiated areas. There is also the potential to transfer cranial bone as a composite temporoparietal osteofascial free flap to the hand. There has been partial flap necrosis and permanent alopecia at the donor site in only 1 of 12 patients. We recommend this flap based on our experience in these 12 patients. PMID- 3347664 TI - A prosthesis to camouflage indented scars. AB - Traditional silicone prostheses have been found to be inflexible, heavy, and of poor color match when used on the limbs. Ten patients distressed by contour deformities on their limbs after the wide excision of malignancies or following trauma were fitted with a light-weight prosthesis whose special features include a flexible foam backing, an outer tinted skin, and finely feathered edges that draw the eye away from the margins of the defect. The prosthesis sticks dependably to the skin and is particularly effective when worn under stockings or tights. When reviewed, all patients were continuing to use the device. It is a useful alternative to surgical reconstruction in such patients. PMID- 3347665 TI - Skin sensation after suction lipectomy: a prospective study of 50 consecutive patients. AB - Using a reproducible pain stimulus, skin sensation was evaluated in a prospective study of 50 consecutive patients who underwent suction lipectomy. A total of 294 anatomic areas were evaluated and treated. Before operation, many patients were found to have patchy areas of decreased sensation, a condition that was unknown to them. Initially after surgery, all patients had decreased sensation in the treated areas. However, sensation usually returned to normal in 6 to 8 months. In some patients, sensory return to preoperative levels took as long as 1 year, and in a few, patchy areas of decreased sensation were present even longer. In general, the larger the treated area, the larger are the area and degree of sensory loss and the slower is the return of sensation. PMID- 3347666 TI - Effects of phenylephrine on tissue gas tension, bleeding, infection, and lidocaine absorption. AB - In an attempt to find a vasoconstrictor with less detrimental local and systemic effects than epinephrine, the effects of phenylephrine, a pure alpha agonist, on tissue gas tension, bleeding, infection rates, and lidocaine absorption were studied. All concentrations of phenylephrine significantly reduced tissue PO2 within 10 minutes of injection, and reduction of PO2 was dose-dependent. Phenylephrine 1:10,000 produced significant bacterial growth when simultaneously injected with 6 X 10(6) Staphylococcus aureus. Bacterial growth was insignificant with 1:20,000 phenylephrine and absent with 1:40,000 phenylephrine. Blood loss from a standard wound was significantly reduced at all concentrations of phenylephrine. Lidocaine absorption was significantly reduced with 1:20,000 and 1:40,000 phenylephrine. In a rat model, 1:40,000 phenylephrine significantly reduced blood loss and lidocaine absorption, produced minimal reduction of tissue PO2, and did not enhance bacterial invasion. PMID- 3347667 TI - The nontypical gluteus maximus flap. AB - Since 1984, 42 patients have been treated with gluteus maximus myocutaneous flaps. In 37 patients, a "classical" gluteus maximus myocutaneous flap was used to cover a sacral-gluteal defect. In 5 patients, a "nontypical" gluteus maximus myocutaneous flap was used: two flaps were advanced from caudal to cranial to close defects over the lumbar spinal area, two flaps were advanced from cranial to caudal to close defects in the perineal region, and one flap was advanced from medial to lateral to close a trochanteric defect. All defects could be closed. There was no flap necrosis. In 12 patients (out of 42) there were minor wound infections, and in 6 patients there were minor wound dehiscences. The average blood loss never exceeded 500 cc, the average time of hospitalization (postoperatively) was 17 days, and mobilization (walking) was started 3 to 4 days postoperatively. The average distance of flap advancement was 10 cm. The maximum defect closed by a bilateral V-Y gluteus maximus myocutaneous flap was 24 x 20 cm. PMID- 3347668 TI - Varix of the digit. AB - Varix of the digit is a rarely described lesion. Over 3 years, eight patients were diagnosed as having this abnormality. Surgical confirmation of the identity of the lesion was accomplished in six of these patients. Repetitive trauma, mechanical compression, and aging phlebectasia have all been associated with the pathogenesis of a digital varix. Thrombophlebitic and thrombotic changes occurring within the varix may lead to an erroneous assessment and clinical confusion. In such instances, a tourniquet test has been useful in demonstrating the presence of a varix. Excision of a symptomatic lesion has proven to be curative for all six patients. Two patients have been observed for 3 years with little change and no resolution of the varix. It is probable that varix of the digit is a more common lesion than indicated by a review of the literature. PMID- 3347669 TI - Blaming the patient. PMID- 3347670 TI - The cessation of cervical nerve root pain following modified SMAS rhytidectomy. AB - The cessation of cervical nerve root pain following modified SMAS rhytidectomy is reported. CAT scans and radiographs demonstrating substantial changes in the intervertebral relationships are documented. No previous report exists demonstrating the biomechanical response to platysma muscle surgery. The potential for alterations in the cervical spine either positive, as in this case, or perhaps negative with exacerbation or creation of symptoms not existing prior to surgery, is presented. The complex biomechanical influence of the procedure indicates that further study and appreciation of the biomechanical changes are necessary to thoroughly understand the ramifications of the SMAS rhytidectomy. PMID- 3347671 TI - Laser silicone flash. AB - Use of the CO2 laser to remove breast siliconosis is described. The flash accompanying this use of the laser is described, and a photograph is submitted to document this previously undescribed phenomenon. PMID- 3347672 TI - Correction of cryptotia using tissue expansion. AB - The anatomy and surgical correction of cryptotia are reviewed. Another technical procedure using retroauricular tissue expansion is presented. This method allows release of the auricle and construction of the auriculocephalic sulcus without the problems associated with older soft-tissue techniques, e.g., incomplete correction, multiple scars, poor color match of skin grafts, and donor-site morbidity. PMID- 3347673 TI - Magna-Site tissue expander: an innovation for injection site location. AB - The Magna-Site tissue expander simplifies the use of tissue expanders by facilitating the location of the injection port, thereby reducing the risks associated with faulty injection placement in the past. The injection port is smooth except for the innocuous palpation bumps, drastically reducing the problems of erosion at the injection port site encountered in the past. No drawbacks were encountered with the use of this expander relative to the use of other currently marketed expanders. The new product is available at a cost similar to expanders currently available. It is felt by the authors that this expander represents the next logical step in the evolution of this technology. Just as Dr. Cohen thought, "It will be exciting to see what new devices are created to further enhance the concept of tissue expansion." PMID- 3347674 TI - An ideal headlamp for overseas surgery. AB - A battery-powered headlamp with a point-source halogen bulb and rechargeable batteries is ideal for operating in underdeveloped facilities. It offers a coaxial light source that rivals the quality of fiberoptic illumination. PMID- 3347675 TI - Surgical follow-up: partial-thickness skin excision for dyskeratoses. PMID- 3347676 TI - Vasoactive intestinal peptide and compression neuropathy. PMID- 3347678 TI - Use of external reservoirs in tissue expansion. PMID- 3347677 TI - A miniature suction head: a new use for the Sahli hemoglobin pipette. PMID- 3347679 TI - A simple minisuction cannula. PMID- 3347680 TI - Senile ectropion. PMID- 3347681 TI - Displaced inframammary fold after Meme breast augmentation. PMID- 3347682 TI - The future of psychoanalysis. PMID- 3347683 TI - Our changing views of the therapeutic action of psychoanalysis: comparing Strachey and Loewald. AB - A comparison of Strachey and Loewald on the nature of therapeutic action reveals a deep shift in analytic interest away from the structural point of view and toward object relational and interpersonal frames of reference. Loewald's theoretical and technical revisions are far more sweeping than is usually acknowledged, and we can better benefit from his contribution by recognizing the full extent of his originality. Loewald's work also illuminates a major challenge for contemporary psychoanalysis: the need for an integration of the now disparate languages of metapsychology and clinical process. PMID- 3347684 TI - A woman's homosexual transference with a male analyst. AB - A woman in analysis with a male analyst developed a significant homosexual transference during the middle phase of treatment. The expression and working through of this material (in displacement) is seen as reflecting one example of the influence of gender on the psychoanalytic process. For the male analyst to utilize this transference, he must make a clear distinction between the negative oedipal phase and the preoedipal (pregenital) phase in female development. PMID- 3347685 TI - Envy, identification, and pride. AB - The constituents of the complex affective experience of envy are delineated, and defenses against each of these constituents are explored. Attention is then called to a common, variably adaptive, and socially approved means of obviating or coping with envious feelings, involving a partial identification and culminating in the conscious experience of "being proud of." A conjecture is made regarding the kind of pathology most likely to interfere with this mechanism. PMID- 3347686 TI - On the vicissitudes of Freud's early mothering. II: Alienation from his biological mother. AB - Continuing an exploration of the vicissitudes of Freud's early mothering experience, this paper utilizes three clinical examples to focus on alienation between Freud and his biological mother. This state of affairs is demonstrated in his reticence about her, his concern about dying before her, and, finally, in his perception of daughter Anna's being his surrogate mourner at the time of his mother's death. PMID- 3347687 TI - A modern "solution" to the oedipal problem: a fantasy of surrogate motherhood. PMID- 3347688 TI - Biases resulting from the use of indexes: an application to attributional style and depression. PMID- 3347689 TI - The relationship between urea and pyrimidine de novo synthesis in ruminant liver. AB - The influence of ammonia and inhibition of the urea cycle by norvaline on orotic acid synthesis in five Polish Merino ewes was investigated. The sheep were exposed to 60 min of successive infusions of 0.9% NaCl, NH4Cl (20 mumol kg-1 min 1), and NH4Cl with DL-norvaline (10 mumol kg-1 min-1) solutions administered to the mesenteric vein. The average rate of orotic acid output, urea output and ammonia uptake in the liver in control conditions (infusion of 0.9% NaCl) was: 1.09 nmol g-1 min-1, 0.97 mumol g-1 min-1 and 0.94 mumol g-1 min-1, respectively. Ammonia significantly stimulated the orotic acid output, urea output and ammonia uptake. At the same time liver uptake of glutamic acid, alanine and glycine increased. Norvaline as a competitive inhibitor of ornithine transcarbamylase depressed citrulline release and urea output in the liver, and elevated, although not significantly, the orotic acid output. It was concluded that ammonia stimulates the de novo synthesis of pyrimidine in the sheep liver but the participation in this effect of carbamyl phosphate generated in the urea cycle is limited. PMID- 3347690 TI - Transport of selenate and sulphate across the intestinal brush-border membrane of pig jejunum by two common mechanism. AB - The objectives of the present study were to find out whether selenate and sulphate are transported by a common Na+-dependent transport mechanism across the intestinal brush-border membrane and whether selenate is also transported by the anion-exchange system transporting sulphate across the brush-border membrane. Results from cis-inhibition as well as from trans-stimulation experiments show that selenate and sulphate are transported across the brush-border membrane by both Na+ co-transport and anion exchange. The influence of various dicarboxylates (oxalate, oxaloacetate, glutamate) and of the anion-exchange inhibitor 4,4' diisothiocyanostilbene-2,2'-disulphonate (DIDS) on selenate and sulphate transport across the brush-border membrane was also investigated. Under Na+ gradient conditions selenate uptake across the brush-border membrane was reduced by oxalate and oxaloacetate but not by L-glutamate or L-leucine. Additionally sulphate uptake under this condition was significantly inhibited by oxalate (about 50%) and DIDS (25%). Sulphate transport by anion exchange was inhibited about 80% by both oxalate and DIDS. These results suggest that under Na+-gradient conditions sulphate (selenate) uptake in part occurs via anion exchange. Furthermore, oxalate seems to inhibit both Na+-sulphate (selenate) co-transport and sulphate (selenate) transport by anion exchange. PMID- 3347691 TI - Catecholamines and dopamine-beta-hydroxylase secretion from perfused goat adrenal glands. AB - Splanchnic nerve stimulation caused a frequency-dependent increase in catecholamine (CA) secretion which attained a maximum at 10 Hz in perfused goat adrenal glands. Acetylcholine (ACh) and nicotine also caused a dose-dependent increase in CA secretion. The percentage of three catecholamines released (adrenaline, 51-56%; noradrenaline, 42-47%; dopamine, 1.3-2%) were not significantly different among three different stimuli. These values were almost the same as those found in the extract of adrenal gland and in purified chromaffin granules. The response to ACh was completely abolished by hexamethonium alone. Pilocarpine was ineffective in increasing CA secretion. Dopamine-beta-hydroxylase (DBH) activity increased with the increase in CA secretion in response to splanchnic nerve stimulation and ACh, though the declining phase of DBH was much slower than that of CA. The ratios of CA to DBH activity released for 25 min during and after splanchnic nerve stimulation and ACh infusion were 0.40 +/- 0.07 and 0.50 +/- 0.07, respectively. The ratio was 0.41 +/- 0.06 in chromaffin granules. The results indicate that only nicotinic receptors are involved in CA secretion and that DBH may be useful as an index of exocytosis in goat perfused adrenal glands. PMID- 3347692 TI - Comparison of force-velocity characteristics obtained using twitches and tetani from in situ rat skeletal muscles. AB - Force-velocity and power-velocity characteristics of three different rat skeletal muscle-tendon complexes (soleus, extensor digitorum longus and medial gastrocnemius) were obtained using twitch and tetanic contractions. No differences were found between twitches and tetani with respect to the shape of the force-velocity curves, or to the velocity at which the highest power output occurs. The results indicate that twitch contractions can be used to standardize muscle preparations in experiments aimed to study muscle energetics during dynamic contractions. PMID- 3347693 TI - Is VIP the putative non-cholinergic, non-adrenergic neurotransmitter controlling protein secretion in rat lacrimal glands? AB - In the combined presence of cholinergic and adrenergic antagonists, electrical field stimulation (FS) caused a marked reversible increase in protein output from superfused rat lacrimal gland segments. The FS-evoked protein output was abolished by the nerve blocking drug tetrodotoxin (TTX; 10(-6) M) whereas high potassium (K+; 100 mM) continued to elicit secretion. Vasoactive intestinal polypeptide (VIP), but not adenosine 5'-triphosphate (ATP), stimulated protein secretion in a manner almost identical to that observed in response to FS. The results suggest that the non-cholinergic, non-adrenergic secretory response may involve VIP as an endogenous neurotransmitter. PMID- 3347694 TI - Temperature-dependence of a fast motile response in isolated outer hair cells of the guinea-pig cochlea. AB - Isolated outer hair cells (OHC) of the cochlea exhibit a motility which can be driven at acoustic frequencies (Ashmore, 1987). The temperature-dependence of the movement is reported here for the range 20-37 degrees C. OHC are shown to be motile at 37 degrees C. The temperature-dependence is quite weak, with Q10 = 1.33. The observation is difficult to reconcile with mechanisms involving an intermediate biochemical messenger, including those based on actomyosin. PMID- 3347695 TI - Magnesium metabolism in the rumens of lactating dairy cows fed on spring grass. AB - Six rumen cannulated lactating Jersey cows were used to study the effects of an abrupt change from a dry diet to young spring grass on mineral metabolism in the rumen, on plasma Mg2+ levels and on water intake. There was an increase in the intake of dietary Mg2+ and concentration of ultrafilterable Mg2+ in rumen fluid when the grass was fed associated with a fall in plasma Mg2+ concentration and percentage urinary Mg2+ excretion. The pH of rumen fluid fell when the cows were fed grass and there was a close inverse relationship with the concentration of ultrafilterable Mg2+ and Ca2+. Changes occurred in the mineral composition of rumen fluid that interact to affect the absorption of Mg2+. The concentrations of NH3, ultrafilterable K+ and ultrafilterable Ca2+ increased and the concentration of ultrafilterable Na+ decreased. These changes were associated with an increase in the potential difference between rumen fluid and blood (positive). Water consumption fell abruptly when the grass was fed and some cows drank no water on several days. However, total water intake was almost doubled resulting in an increased rumen volume. PMID- 3347696 TI - Synovial fluid--its mass, macromolecular content and pressure in major limb joints of the rabbit. AB - Synovial fluid from rabbit elbow, shoulder, hip and knee was analysed to establish the normal levels of parameters relevant to fluid exchange viz. fluid mass per joint, hydraulic pressure, temperature, colloid osmotic pressure (COP), protein, albumin and glycosaminoglycan (GAG) concentrations. Fluid mass was greatest in the least congruous joint, the shoulder (43 +/- 4 mg), cf. 6 +/- 2 mg in the highly congruous hip. In the knee (24 +/- 4 mg) the mean thickness of the fluid layer was calculated to be 30 microns. Fluid pressure was subatmospheric in all joints (mean -2.8 +/- 0.4 cmH2O, elbow, to -5.7 +/- 0.3 cmH2O, knee), as in many other interstitial spaces. Colloid osmotic pressure was substantial (mean 11.4 +/- 0.9 cmH2O, shoulder, to 13.1 +/- 1.0 cmH2O, elbow), being 40-46% of serum level. Comparison of synovial fluid results with COP versus concentration curves in vitro indicated that the fluid's COP was primarily generated by its protein content (22-30 g l-1, 64% albumin) rather than GAG (4.0-5.8 g l-1). The GAG was 95% hyaluronate and 5% sulphated GAG. Algebraic summation of the hydraulic and colloid osmotic pressures of synovial fluid and serum indicated a net filtration gradient from blood to joint cavity. When serum COP was reduced by intravenous saline infusion, synovial fluid mass increased, in accordance with the ultrafiltration hypothesis of synovial fluid formation. The fluid's colloid concentration declined as volume increased. The relation was not a simple dilution curve, but indicated that the newly formed synovial fluid contained greater than or equal to 8 g protein l-1 (14.5% serum concentration); and that hyaluronate was entering the synovial cavity at a rate of greater than or equal to 6.5 micrograms h-1 per joint. PMID- 3347697 TI - Relation between trans-synovial flow and plasma osmotic pressure, with an estimation of the albumin reflection coefficient in the rabbit knee. AB - The volume of synovial fluid in a joint correlates inversely with plasma colloid osmotic pressure (COP). The inferred influence of plasma osmotic forces on trans synovial flow was investigated directly here, in isolated perfused hindquarters of sixteen rabbits. Flow of intra-articularly infused Krebs solution across the synovial lining of the cannulated knee was recorded at controlled intra-articular pressure (18 cmH2O). Colloid osmotic pressure in the synovial microcirculation was varied by perfusion with oxygenated red cells resuspended in albumin solution or plasma from an extra-corporeal system at constant perfusion pressure. Studies in vitro showed that the COP versus concentration curve for commercial bovine albumin samples was variable and not reliably described by a widely used polynomial. The rate of trans-synovial absorption Qs was a positive linear function of intravascular COP pi p (r = 0.936, P less than 0.001, n = 83). The average slope dQs/d pi p was 0.20 microliter min-1 cmH2O-1 (S.E. +/- 0.01 microliter min-1 cmH2O-1), the slope depending on hydraulic conductance and osmotic reflection coefficient. Trans-synovial flow was a negative linear function of synovial capillary pressure (Pc). Absolute slope dQs/d pi p was on average only 78% of dQs/dPc in the same joint. The osmotic reflection coefficient of the blood-joint barrier to serum albumin was estimated from these slopes as 0.78-0.81 (S.E.M. +/- 0.06). Vascular perfusion with a hyperosmolar solution of glucose, sucrose or NaCl generated a transient, rapidly decaying osmotic absorption from the joint cavity, with a half-life of 17-60 s. A reversed osmotic transient occurred on reperfusion with isotonic fluid. It was concluded that the blood-joint barrier, which comprises fenestrated endothelium and synovial intima, approximates to an imperfect semipermeable membrane for albumin solutions, justifying the application of Starling's hypothesis to trans-synovial flow. For small solutes the tissues form a highly permeable but nevertheless slightly osmotically reflective membrane. PMID- 3347698 TI - The role of the abdominal visceral innervation and 5-hydroxytryptamine M receptors in vomiting induced by the cytotoxic drugs cyclophosphamide and cis platin in the ferret. AB - We have used the ferret as an animal model to investigate the emetic action of the cytotoxic drugs cyclophosphamide and cis-platin. Using selective nerve lesions, a crucial role for the abdominal innervation in the genesis of retching and vomiting in response to these agents has been demonstrated. A combination of bilateral abdominal vagotomy and greater splanchnic nerve section can totally abolish retching and vomiting in response to intraperitoneal cis-platin or intravenous cyclophosphamide. Intraperitoneal cyclophosphamide still produced retching but vomiting was markedly reduced, demonstrating complex and probably separate control mechanisms for retching and vomiting. The effect of a widely used anti-emetic, metoclopramide, was compared to that of nerve lesions. While effective this compound did not totally control retching or vomiting to either drug. Recent studies have attributed metoclopramide's action to its ability to antagonize 5-HT M-receptors (5-HT-3 receptors). Therefore we investigated BRL 24924, a gastro-kinetic agent with more specific 5-HT M-receptor antagonist properties. This agent was extremely potent in almost totally abolishing retching and vomiting in response to cyclophosphamide, given by either an intravenous or intraperitoneal route, and totally abolished cis-platin-induced vomiting for at least 4 h. Clearly the abdominal visceral innervation plays a complex and major role in the emesis produced by these two cytotoxic drugs; circumstantial evidence suggests that 5-HT M-receptors on visceral afferent nerves mediate this action, but other possibly central sites of action of the 5-HT M-receptor antagonists cannot be excluded. PMID- 3347699 TI - Retrograde oesophageal contractions in the dog. AB - Retrograde oesophageal contractions were observed by simultaneous radiography and electromyography during naturally occurring post-prandial eructations in six dogs. The contractions progressed cranially at 85 +/- 16 cm s-1 (S.E.M., n = 50) displacing, to the mouth, gastric gas which had previously passed into and distended the thoracic part of the oesophagus for 304 +/- 22 ms (S.E.M., n = 30). Ninety per cent (n = 100) of retrograde oesophageal contractions were followed immediately by a slower aboral contraction (17.1 +/- 0.02 cm s-1; S.E.M., n = 15). This appears to be the first description of naturally occurring retrograde oesophageal contractions in a non-ruminant animal. PMID- 3347700 TI - The effect of acute joint inflammation on flexion reflex excitability in the decerebrate, low-spinal cat. AB - Experiments were performed to investigate whether acute knee joint inflammation, induced by intra-articular injection of carrageenan and kaolin, significantly influences the magnitude of the flexion withdrawal reflex of knee flexors in the decerebrate, low-spinal cat. It was observed that after injection of these inflammatory agents, reflex intensity increased with a time course that matched the development of the inflammatory process, as assessed by monitoring the intra articular temperature. Control experiments involving intra-articular injection of saline showed neither a rise in intra-articular temperature, nor any change in reflex intensity. The normal pattern of modulation of reflex intensity with changing joint angle was abolished in the inflamed joint with the reflex being equally intense at all positions tested. Abolition of neural activity in the inflamed joint by intra-articular injection of lignocaine resulted in a marked decrease in the reflex back to control values, suggesting that there is no maintained increase in central excitability in the absence of joint afferent input. It was also observed that the spontaneous activity of knee flexor motor units was modulated during continuous passive rotation of the knee, with activity being greater in extension than in flexion. This pattern reversed when the knee was acutely inflamed, but could be returned to the control pattern by joint anaesthesia, although now the response was attenuated when compared to the control. PMID- 3347701 TI - Frequency distributions and density functions of distances with simulated linear track structures. AB - Track structures of high-LET particles can be simulated by various linear approaches. The distribution of distances seems to be an important parameter in understanding the type of interactions which occur and the biological effects which these excitations and ionizations will create; therefore, the distance distributions of these simulated track structures were calculated. Three presentations show that their exact appearance depends on the scaling parameter: the number of classes. In one approach the theoretical density of the distances was calculated by the techniques of convolution and by forming mixed distributions which confirm the findings of the simulation. PMID- 3347702 TI - Oxygen dependence of product formation in irradiated adenosine 5'-monophosphate. AB - The formation of (R)- and (S)-8,5'-cycloadenosine 5'-monophosphate (8,5' cycloAMP), 8-hydroxyadenosine 5'-monophosphate (8-hydroxyAMP), and radiolytic adenine release from irradiated solutions of adenosine 5'-monophosphate (5'-AMP) was measured as a function of increasing liquid-phase oxygen concentration. Three classes of specific molecular damage were identified on the basis of the oxygen dependence for product formation. Major changes in product yield occurred near the range of oxygen concentrations associated with the radiobiological oxygen effect. In addition to these data, systematic increases in the concentration of hydrogen peroxide at the time of irradiation resulted in an increase in the yield of 8-hydroxyAMP and a component of radiolytic adenine release in nitrogen saturated solutions of 5'-AMP. However, no changes in the yield of the 8,5' cyclonucleotides were observed under these conditions. PMID- 3347703 TI - The effects of reduced temperature and/or starvation conditions on the radiosensitivity and repair of potentially lethal damage and sublethal damage in L5178Y-R and L5178Y-S cells. AB - Potentially lethal damage (PLD) and sublethal damage (SLD) modification in L5178Y S(LY-S) and L5178Y-R (LY-R) cells was investigated for postirradiation holding in either plateau phase or log phase at either 25 or 37 degrees C. Incubation in both plateau and log phases increased PLD repair (PLDR) at 25 degrees C but increased PLD fixation (PLDF) at 37 degrees C in LY-S cells, with the opposite result (PLDR at 37 degrees C, PLDF at 25 degrees C) in LY-R cells. Conditioned medium (CM from plateau-phase cells) had only a slight effect on the radiosensitivity of log-phase LY-S cells. CM was highly toxic to log-phase LY-R cells even without radiation. Postirradiation incubation of log-phase cells at 25 degrees C increased PLDF between 5.5 and 18 h in LY-R cells, whereas PLDR was completed by 5.5 h in LY-S cells. Flow cytometric data show that the LY-R vs LY-S plateau-phase PLD results are not caused by a differential cell cycle distribution. Although all cell cycle stages are found in the plateau-phase cells, G1 is enriched and cells in all stages must be slowly cycling or stationary. Split doses decrease survival of LY-S cells at 37 degrees C but maintain survival at the single acute total dose level at 25 degrees C (no SLD repair (SLDR)). SLDR is observed at both 25 and 37 degrees C in LY-R cells. The results for both the split dose and delayed plating experiments are best understood in terms of competition between PLD repair and fixation with their relative contributions depending on cellular metabolism, which can be altered by changes in temperature or medium constituents. The opposite PLD results obtained for LY-S and LY-R cells suggest that radiosensitivity in these cells is determined by two different mechanisms. PMID- 3347704 TI - Depletion of the spermatogonia from the seminiferous epithelium of the rhesus monkey after X irradiation. AB - In unirradiated testes large differences were found in the total number of spermatogonia among different monkeys, but the number of spermatogonia in the right and the left testes of the same monkey appeared to be rather similar. During the first 11 days after irradiation with 0.5 to 4.0 Gy of X rays the number of Apale spermatogonia (Ap) decreased to about 13% of the control level, while the number of Adark spermatogonia (Ad) did not change significantly. A significant decrease in the number of Ad spermatogonia was seen at Day 14 together with a significant increase in the number of Ap spermatogonia. It was concluded that the resting Ad spermatogonia are activated into proliferating Ap spermatogonia. After Day 16 the number of both Ap and Ad spermatogonia decreased to low levels. Apparently the new Ap spermatogonia were formed by lethally irradiated Ad spermatogonia and degenerated while attempting to divide. The activation of the Ad spermatogonia was found to take place throughout the cycle of the seminiferous epithelium. Serum FSH, LH, and testosterone levels were measured before and after irradiation. Serum FSH levels already had increased during the first week after irradiation to 160% of the control level. Serum LH levels increased between 18 and 25 days after irradiation. Serum testosterone levels did not change at all. The results found in the rhesus monkey are in line with those found in humans, but due to the presence of Ad spermatogonia they differ from those obtained in non-primates. PMID- 3347705 TI - Repopulation of the seminiferous epithelium of the rhesus monkey after X irradiation. AB - Repopulation of the seminiferous epithelium became evident from Day 75 postirradiation onward after doses of 0.5, 1.0, and 2.0 Gy of X rays. Cell counts in cross sections of seminiferous tubules revealed that during this repopulation the numbers of Apale (Ap) spermatogonia, Adark (Ad) spermatogonia, and B spermatogonia increased simultaneously. After 0.5 Gy the number of spermatogonia increased from approximately 10% of the control level at Day 44 to 90% at Day 200. After 1.0 and 2.0 Gy the numbers of spermatogonia increased from less than 5% at Day 44 to 70% at Days 200 and 370. The number of Ad and B spermatogonia, which are considered to be resting and differentiating spermatogonia, respectively, already had increased when the number of proliferating Ap spermatogonia was still very low. This early inactivation and differentiation of a large part of the population of Ap spermatogonia slows down repopulation of the seminiferous epithelium of the primates. By studying repopulating colonies in whole mounts of seminiferous tubules various types of colonies were found. In colonies consisting of only A spermatogonia, 40% of the A spermatogonia were found to be of the Ad type, which indicates that even before the colony had differentiated, 40% of the A spermatogonia were inactivated into Ad. Differentiating colonies were also found in which one or two generations of germ cells were missing. In some of those colonies it was found that the Ap spermatogonia did not form any B spermatogonia during one or two cycles of the seminiferous epithelium, while in other colonies all Ap spermatogonia present had differentiated into B spermatogonia. This indicates that the differentiation of Ap into B spermatogonia is a stochastic process. When after irradiation the density of the spermatogonia in the epithelium was very low, it could be seen that the populations of Ap and Ad spermatogonia are composed of clones of single, paired, and aligned spermatogonia, which are very similar to the clones of undifferentiated spermatogonia in non-primates. PMID- 3347706 TI - Growth factors and hyperthermia. I. The relationship between hyperthermic cell killing and the mitogenic response to serum and growth factors. AB - Chinese hamster ovary HA-1 cells were tested for their ability to respond to mitogenic stimulation after hyperthermia at 45 degrees C. Cells were arrested by 24 h incubation in serum-free Eagle's MEM. Heating of arrested cells in serum free medium did not alter heat sensitivity compared to exponentially growing cells heated in serum-containing medium. After hyperthermia cells exhibited a delay in the ability to undergo mitogenesis. Recovery of the capacity for mitogenesis occurred during the 24 h following heating and was able to take place in the absence of serum. After recovery in serum-free medium, cells were simultaneously assayed for survival and mitogenesis as measured by [3H]Thy uptake. With increasing heating time, surviving fraction and mitogenesis decreased. The reduction in survival was similar to the reduction in [3H]Thy incorporation. The relationship between mitogenesis and cell death was studied in more detail with flow cytometry. At a relatively mild heat dose of 30 min at 45 degrees C (survival = 30%), a small population of cells (9%) was found to be clonogenically dead yet capable of being stimulated to progress from G1 to G2-M. At a more severe heat dose of 40 min at 45 degrees C (survival = 3%), stimulation of dead cells could not be detected. Therefore, hyperthermia impairs mitogenic ability, but at low heat doses, a subpopulation of killed cells can still be stimulated to progress through the cell cycle. PMID- 3347707 TI - Isolation and characterization of heat-sensitive, thermotolerant defective mutants of CHO cells. AB - A replica plating technique was utilized to isolate stable CHO cell mutants that are heat-sensitive and have altered capacities to develop thermotolerance. From a mutagen (EMS) treated population of CHO cells, two strains were isolated. One (HS 36) shows a greatly reduced ability to develop thermotolerance following an initial 45.0 degrees C heat shock. The other (HS-23) also shows a greatly reduced thermotolerance development following a short 45.0 degrees C induction dose, but a greater thermotolerance development following longer 45.0 degrees C induction doses. The dose-survival response following single-dose 45.0 degrees C heating of HS-23 cells suggests the presence of a resistant subpopulation which is not due to contamination from, or reversion to, wild-type cells. Both strains have unique morphological characteristics. Spheroids develop in the central portion of HS-36 colonies, though cells in monolayers are indistinguishable from wild-type parental cells. HS-23 cells grow in firmly attached monolayers, but more than 95% maintain a "rounded" morphology. The remainder show a "flattened" morphology typical of CHO cells. Both strains have parental CHO characteristics as determined by chromosome number, population doubling times, and survival responses to UV light and to gamma rays. Each has maintained its heat-sensitive and altered thermotolerance phenotype for a period of over 6 months in continuous log-phase culture. PMID- 3347708 TI - Wavelength dependence for human redoxy-endonuclease-mediated DNA cleavage at sites of UV-induced photoproducts. AB - Redoxy-endonuclease, an enzyme present in human and other cells, recognizes monobasic photoproducts that occur primarily at sites of cytosine following UV irradiation of DNA at 254 nm. The wavelength dependence for formation of these photoproducts was determined using end-labeled DNA fragments of defined sequence irradiated with monochromatic light ranging from 254-360 nm as substrates for redoxy-endonuclease partially purified from HeLa cells. The base specificity and extent of DNA cleavage were determined by analysis of the enzyme-generated DNA scission products on DNA sequencing gels. Maximal incision at sites of cytosine and thymine was observed at 280 nm, suggesting that these photoproducts may be relevant with respect to the biological effects of solar radiation. PMID- 3347709 TI - Lung cancer: differentiation of tumor, necrosis, and atelectasis by means of T1 and T2 values measured in vitro. AB - In vitro measurements of T1 and T2 values were performed in surgical specimens from 15 patients with lung cancer. Correlation between histologic results and measured values revealed that different pathologic tissues can be characterized by means of T1 and T2 values. The transverse magnetization decay curve of the lung tissue was multiexponential, which can be explained by two different relaxation times, fast T2 and slow T2. The signal intensity of pathologic lung tissues at different pulse sequences was simulated on a signal intensity gradient graph based on measured values of T1, fast T2, slow T2, and water content. The results showed that T2-weighted sequences were more valuable in discriminating viable lung cancer from necrotic tumor and collapsed lung lesions. PMID- 3347710 TI - Aneurysms of the right ventricular outflow tract after tetralogy of Fallot repair: role of radiology. AB - Eight patients with aneurysms of the right ventricular outflow tract patch following tetralogy of Fallot repair were found to have residual distal obstructions. The site of such an obstruction must be carefully documented preoperatively because failure to relieve significant distal obstruction may result in recurrent aneurysm formation. Chest radiography; echocardiography, including Doppler analysis; and cardiac catheterization, including angiocardiography, each have a role in the detection and evaluation of this complication. PMID- 3347711 TI - Acute myocardial ischemia: MR imaging with Mn-TP. AB - Cardiac-gated magnetic resonance (MR) imaging was performed in rats to determine the effects of manganese ethylenediaminetetraphosphonate (TP). Ten normal rats received Mn-TP in a dose of 50 mumol/kg through a tail-vein injection. Spin-echo MR images were obtained before and every 10 minutes after Mn-TP injection for 1 hour. Cardiac signal intensity (SI) increased more than 70% after Mn-TP injection and remained nearly unchanged 1 hour after injection. Myocardial T1 was 517 +/- 49 msec in eight control rats and 282 +/- 61 msec (P less than .001) in six rats 81 +/- 0 minutes after injection. Nine rats underwent occlusion of the left anterior descending coronary artery prior to MR imaging. Images were obtained before and 15, 30, and 60 minutes after Mn-TP injection. In normal myocardium, SI increased up to 82% and remained elevated for 1 hour. In ischemic myocardium, SI rose 11%, leading to a marked contrast between the two tissue zones. T1 was also different in the two regions: In normal tissue, it was 206 msec +/- 54; in ischemic tissue, 338 +/- 82 (P less than .001). With T1-weighted MR imaging, Mn TP showed a potential for delineating the jeopardized area after acute myocardial ischemia. PMID- 3347713 TI - Febrile infants less than 3 months old: value of chest radiography. AB - In the febrile infant less than 3 months old, a chest radiograph is commonly obtained to identify the cause of the fever. The purpose of this study was to evaluate the necessity of obtaining chest radiographs in this population. The clinical records and chest radiographs of 192 febrile infants (greater than 100.5 degrees F, rectal) were reviewed. Nineteen patients had signs of respiratory distress; seven had positive findings on chest radiographs. Of the 173 patients without signs of respiratory distress, five had positive findings on chest radiographs. When chest radiography was considered the gold standard for the presence or absence of pneumonia, findings of respiratory distress on physical examination had a sensitivity of 58% and a specificity of 93% for the detection of pneumonia. The prevalence of positive findings on chest radiographs in febrile infants less than 3 months old was 6%. A chest radiograph should be obtained in febrile infants only when signs of respiratory distress are present. PMID- 3347712 TI - Periappendiceal inflammatory masses: CT-directed management and clinical outcome in 70 patients. AB - The outcome was reviewed in 70 patients with computed tomographic (CT) and clinical evidence of periappendiceal inflammatory masses. On the basis of the initial CT scan, patients were divided into three broad categories: (a) patients with periappendiceal phlegmons or abscesses less than 3 cm (n = 32); (b) patients with well-defined and well-localized periappendiceal abscesses greater than 3 cm (n = 28); and (c) patients with extensive, poorly defined periappendiceal abscesses with either pelvic, retroperitoneal, or interloop involvement (n = 10). Thirty-two patients with either phlegmons or small abscesses were treated initially with antibiotic therapy alone; clinical resolution of the inflammatory process occurred in 28 patients (88%). Twenty-eight patients with well-defined and well-localized periappendiceal abscesses underwent percutaneous catheter drainage, which was successful in 26 patients (93%). Nine of ten patients underwent early surgical drainage for extensive, poorly defined abscesses. One patient underwent percutaneous drainage as a temporizing measure before surgery. There were three false-positive CT diagnoses of periappendiceal abscesses in this series. PMID- 3347714 TI - The "trumpeting elephant" sign of gastroesophageal reflux. PMID- 3347715 TI - Operational radiologic image archive on digital optical disks. AB - A digital optical disk archive for storage of computed radiographic, computed tomographic, magnetic resonance, ultrasonographic, and digitized film radiographic images was installed. In the system, digital images enter a minicomputer, are temporarily stored on magnetic disks, and are archived onto write-once read-many optical disks at their full resolution. A pictorial index of minified images is maintained for each patient. After 8 months of operation, 49,400 megabytes of images had been retained on 19 optical disks stored, after January 1987, in a mechanical jukebox-style optical disk library. The success rate for archival capture of images during the initial period was 96.6%. The failures were due to overfilling of the magnetic disk, a problem addressed through the addition of a second magnetic disk unit. There were no medium-related image errors during the early period. Problems resulting from the slow speed of optical disk systems were addressed operationally by initiating recall of a patient's archived images from the optical to the faster magnetic disk as soon as the system received a request to acquire a new image. Also, optical disk retrieval times are expected to improve with technologic development. PMID- 3347716 TI - Three-dimensional quantitative CT of the proximal femur: relationship to vertebral trabecular bone density in postmenopausal women. AB - Dual-photon absorptiometry (DPA) of the proximal femur cannot independently measure cortical and high-turnover cancellous bone. In this investigation, integrated cancellous, cortical, and total bone densities in the femoral neck and intertrochanteric region were measured bilaterally in 22 women aged 42-75 years. Contiguous section data were analyzed with two different protocols by means of three-dimensional histogram software. Single-section quantitative computed tomography (CT) was used to determine mean mineral equivalent values for vertebral cancellous bone from T-11 to L-3 in each woman. Significant correlation was found between cancellous bone density at the two sites, as well as between total femoral and vertebral measurements. Femoral cortical bone density was predicted less well by means of the vertebral cancellous data. Cortical, cancellous, and total proximal femoral density values tended to exhibit bilateral symmetry. Quantitative three-dimensional volumetric CT affords comprehensive evaluation of proximal femoral mineral status because of its capability for selective measurement of cortical, cancellous, and total bone density. PMID- 3347718 TI - Intraosseous lipomas: radiologic and pathologic manifestations. AB - Sixty-one cases of surgically treated solitary intraosseous lipoma were staged into three categories depending on the degree of involution present histologically: stage 1, tumors of viable fat cells; stage 2, transitional cases composed partly of viable fat cells but also demonstrating fat necrosis and calcification; and stage 3, lesions demonstrating necrotic fat, calcification of necrotic fat, variable degrees of cyst formation, and reactive woven bone formation. Each of these stages had radiologic features that could be correlated with the histopathologic findings in the excised tissue. Examples of stage 3 lesions have frequently been misdiagnosed as unusual bone infarcts or other lesions. Intraosseous lipoma may be a less rare lesion than has previously been suggested. PMID- 3347717 TI - Comparison of bone mineral density in both hips. AB - Dual-photon absorptiometry (DPA) was performed on both hips of 40 patients to determine if the calculated bone-mineral density (BMD) of one hip could be used to predict the BMD of the opposite hip. For the Ward triangle, femoral neck, and greater trochanter the correlation coefficients between the BMD of the two hips was .920, .917, and .843, and the standard errors (SE) of the estimate for the linear regression of the left hip on to the right were 0.067, 0.063, and 0.077 g cm-2. The absolute error of predicting one hip from the other was not a function of BMD and thus the relative error increases with lower BMD values. The relative errors were 17%, 8%, and 7% for BMDs of 0.4, 0.8, and 1.0 g cm-2, respectively. The interobserver variability was small, with an r value of .96 and an SE of the estimate value of 0.036 g cm-2. The relative error in the mild-to-moderate osteoporosis categories was 2.5 times the precision of the instrument, indicating that the asymmetry of BMD is due to real differences between hips. Therefore the BMD of one hip cannot be used to predict that of the other with sufficient accuracy to discriminate clinically relevant trends in BMD. PMID- 3347719 TI - Brachial plexus: correlation of MR imaging with CT and pathologic findings. AB - Thirty-two patients with symptoms referable to the brachial plexus were evaluated with magnetic resonance (MR) imaging. Sixteen patients had undergone concurrent computed tomography (CT). MR imaging demonstrated normal findings in 16, 12 neoplasms, three cases of trauma, and one case of possible neural edema. Of the 16 patients with normal findings on MR images, eight had CT scans that were also normal. In one patient, MR images showed that the "mass" seen on CT was actually a tortuous blood vessel. In six of the 12 cases of neoplasm in which CT scans were available, MR imaging revealed more extensive disease. In the other six cases of tumor, MR imaging provided sufficient clinical information to obviate the need for CT or any other imaging modality. MR imaging provided definitive diagnoses in the three cases of trauma without further imaging. In one patient with paresthesia, MR imaging showed high signal intensity of the nerves on T2 weighted images, which was compatible with neural edema. A concurrent CT scan was normal. PMID- 3347720 TI - Adhesive capsulitis of the wrist: arthrographic diagnosis. AB - Persistent pain and decreased range of motion are disabling complications of wrist trauma. Between 1978 and 1986, in ten patients with persistent pain following trauma, arthrography depicted changes characteristic of adhesive capsulitis. Adhesive capsulitis has been described in the shoulder, hip, and ankle, but little mention has been made of this entity in other joints. Confirmation of this diagnosis requires arthrography, since there are no characteristic findings on plain radiographs. Typical arthrographic findings include decreased capacity, small volar and styloid recesses, and adhesions preventing complete opacification of the joint. The arthrographic diagnosis allows proper institution of appropriate therapy. PMID- 3347721 TI - Radiography after orthognathic surgery. Part I. Normal appearance. AB - Osteotomies of the mandible and/or maxilla (orthognathic surgery) are common procedures for correcting facial defects. Radiographs of these patients are routinely obtained, and the radiologist must be aware of the normal postoperative appearance as well as surgical complications that may occur. This article presents the common surgical procedures done (sagittal split, vertical subcondylar, genioplasty mandibular osteotomies; and Le Fort I and mid-palatal split maxillary osteotomies) and the routine appearance of uncomplicated procedures on posteroanterior skull and panoramic radiographs. The metallic immobilization devices and orthodontic appliances are also described. PMID- 3347722 TI - Radiography after orthognathic surgery. Part II. Surgical complications. AB - In a retrospective review of the radiographs from 100 patients who had undergone orthognathic surgery, the authors found that 10% of radiographs had evidence of surgical complications. These complications were fractures, temporomandibular joint dislocations, transected tooth roots, retained surgical devices, avascular necrosis, malunion or nonunion of osteotomy fragments, and osteomyelitis. Some of these complications are of little significance, while others require immediate intervention. Opacified maxillary sinuses and lucencies around tooth roots are frequent findings that may be confused with abnormalities; however, they represent postoperative blood in the sinuses and resorption of bone due to stress from orthodontic appliances, respectively. PMID- 3347723 TI - Invasion of laryngeal cartilage by cancer: comparison of CT and MR imaging. AB - Forty-two patients with laryngeal carcinomas were examined with computed tomography (CT) and magnetic resonance (MR) imaging. The accuracy of both CT and MR imaging in the depiction of cartilage invasion was evaluated in 16 patients by comparing findings at CT and MR with pathologic findings. Calcified cartilage that has been invaded by cancer is frequently seen on CT scans as having an intact contour. Tumor approaching nonossified cartilage may simulate cartilage invasion. On T1-weighted MR images, invaded marrow of ossified cartilage is of intermediate signal intensity, allowing it to be differentiated from normal bone marrow. On proton-density images, tumor is of increased signal intensity, which allows it to be differentiated from nonossified cartilage. In our experience, the specificities of CT and MR imaging were approximately equal (91% and 88%, respectively), but CT had a considerably lower sensitivity than MR (46% vs. 89%). Gross movement artifacts, which resulted in nondiagnostic images, occurred in 16% of the MR examinations. MR imaging is recommended as the modality of choice in the diagnosis of cartilage invasion. PMID- 3347724 TI - Hepatic micrometastases in the rat: ferrite-enhanced MR imaging. AB - A rat tumor model was used to evaluate the ability of ferrite-enhanced magnetic resonance (MR) imaging to demonstrate hepatic metastases smaller than 1 cm. Twenty-eight rat livers were inoculated with 5 X 10(5) mammary carcinoma cells and imaged with a 0.6-T MR system. Non-enhanced and ferrite-enhanced images were analyzed and correlated with autopsy findings for each rat. Lesion detection rates correlated closely with cancer-to-liver contrast-to-noise ratios. Ferrite enhanced MR imaging demonstrated significantly more lesions than non-enhanced imaging (P less than .05) and decreased the threshold size for lesion detectability (less than 2 mm). Ferrite also enabled more accurate measurements of the lesions (r = .96). PMID- 3347725 TI - Malignant extradural spinal tumors: MR imaging with Gd-DTPA. AB - Magnetic resonance (MR) imaging with gadolinium diethylenetriaminepentaacetic acid (DTPA) was performed in 12 patients with neoplasia of the spine and epidural space. Postcontrast images were compared with precontrast images. Gd-DTPA MR images did not improve the detection of tumors affecting the epidural space of the spine. In fact, many lesions were isointense when compared with the intensity of the surrounding bone marrow and were difficult to see. Because of this, contrast material-enhanced images were not sufficient; however, when they were combined with precontrast images, the use of Gd-DTPA improved the delineation and characterization of certain lesions. Gd-DTPA MR images were helpful in differentiating disk herniation from epidural tumors, indicating regions of more active tumor for biopsy, outlining areas of spinal cord compression, and demonstrating tumor response to therapy. Therefore, while it may be unlikely that Gd-DTPA will be used routinely in every case of suspected neoplasia of the epidural space, contrast-enhanced images will undoubtedly have an adjunctive role in certain clinical applications. PMID- 3347726 TI - Lumbar spine: motion compensation for cerebrospinal fluid on MR imaging. AB - To determine whether the motion of cerebrospinal fluid (CSF) in the lumbar spine degrades T2-weighted magnetic resonance (MR) images, a spine phantom, three healthy volunteers, and a prospective series of 20 patients suspected of having lumbar spine disease underwent MR imaging with and without motion-compensation techniques. In the phantom, pulsation amplitudes as low as 3 mm (within the physiologic range of human lumbar CSF motion) reduced image quality on conventional images but not on motion-compensated images. Similar findings were observed in two volunteers and 11 patients. The magnitude of the artifacts was variable; they could impair visualization of the conus, decrease contrast or reduce the sharpness of the CSF-thecal sac interface, and cause focal regions of reduced CSF signal intensity adjacent to bulging disks. Image quality was most improved when peripheral gating was combined with even-echo rephasing. In the patient group, the use of motion-compensation techniques increased the CSF signal to-noise ratio by an average of 29% (P less than .01); this resulted in improved contrast between the conus and extradural structures. The data suggest that CSF motion compensation is clinically useful during T2-weighted MR imaging of the lumbar spine. PMID- 3347727 TI - Nonselective angiography after intracorporal papaverine injection: an alternative technique for evaluating penile arterial integrity. AB - Forty patients with impotence were evaluated by means of nonselective angiography after intracorporal papaverine injection. The penile arterial network was visualized in 39 patients (97%). The technique was technically simple, and there were no complications. The most common sites of arterial disease were the arteries at the base of the penis (58%) and the internal pudendal artery (31%). In patients with advanced atherosclerotic disease, formation of collaterals within the penile arterial network appears to be important in maintaining flow to the cavernosal arteries. Asymmetry of arterial disease was frequently encountered (54%), indicating the importance of bilateral visualization of the arteries supplying the cavernosal arteries. Penile arteries were not visualized adequately in any of the patients studied nonselectively without intracorporal papaverine. PMID- 3347728 TI - Filters for radiation reduction: a comparison. AB - Aluminum, yttrium, copper, and R-filters were evaluated with respect to effective beam energy, entrance radiation exposure to the skin, x-ray tube loading, and the quality of resultant radiographs. Since all filters yielded acceptable radiographs, a figure of merit was developed to determine which filter delivered the lowest entrance radiation exposure for the lowest increase in x-ray tube loading. The figure of merit indicated that the best results were obtained with the 0.1-mm Cu filter with 2 mm Al at 60-105 kVp and with the 0.2-mm Cu filter with 2 mm Al at 105-120 kVp. Cu filters produced radiographs with quality comparable to that of R- or Y filters. Cu filters are inexpensive alternatives to rare-earth filters and yielded a reduction in radiation exposure with less x-ray tube loading. PMID- 3347729 TI - Statement from the 1987 Como meeting of the International Commission on Radiological Protection. PMID- 3347730 TI - Biliary drainage: conversion of external to internal drainage. AB - A percutaneously inserted biliary drainage catheter was converted from external to internal drainage with the use of an additional catheter advanced through the gastrostomy opening. This technique was successful in one patient with unresectable cancer of the head of the pancreas, in whom it was performed to overcome the various disadvantages of external biliary drainage. PMID- 3347731 TI - Inflatable surface coil for MR imaging of the prostate. AB - An inflatable surface coil for transrectal magnetic resonance imaging of the prostate was designed. The coil was tested during imaging of an insulated saline phantom and of the prostates of four patients. Phantom images were comparable to those obtained with commercial coils of similar size. High spatial resolution and excellent contrast were noted in coronal images of the prostates. Use of this coil could substantially improve studies of the prostate and cervix. PMID- 3347732 TI - Visual contrast enhancement with a patterned overlay. AB - A dot-screen pattern was devised and superimposed on computed tomography images to improve contrast at a viewbox. The phenomenon is believed to be probably related to lateral inhibition. To evaluate its usefulness, the device was used on 12 images (eight showed metastatic liver lesions, and four were normal); each image was viewed without the device by ten observers. Three control images were viewed a second time without the device. The remaining nine images were viewed a second time with the device. The overlay improved diagnostic performance in nine observers. Sensitivity improved by 12%, and confidence in true-positive findings increased by 41.6%. Forty-five percent of false-negative findings were converted to true positive with the use of the overlay. PMID- 3347734 TI - Nonpalpable lesions detected with mammography. PMID- 3347733 TI - Spine: device to facilitate surface coil MR imaging. AB - A device was constructed to allow rapid adjustment of the position of a surface coil in magnetic resonance (MR) imaging of the spine. The device consists of two sheets of acrylic plastic and a movable sled. The surface coil is placed on the sled and can be precisely moved superiorly or inferiorly with a cord attached to the sled. The device can save approximately 30 minutes during MR imaging of the entire spine and increases patient comfort and cooperation. PMID- 3347735 TI - Cervical spinal stenosis: determination with vertebral body ratio method. PMID- 3347736 TI - Preoperative chest radiography. PMID- 3347738 TI - Pulmonary metastatic disease: radiologic-surgical correlation. PMID- 3347737 TI - Percutaneous insertion of the Kimray-Greenfield filter. PMID- 3347739 TI - Voice-activated radiology reports. PMID- 3347740 TI - Nonpalpable breast lesions: accuracy of prebiopsy mammographic diagnosis. PMID- 3347741 TI - Colorectal hemangioma: radiologic findings. AB - The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma. PMID- 3347742 TI - Peritoneal carcinomatosis: imaging with intraperitoneal injection of I-131 labeled B72.3 monoclonal antibody. AB - Monoclonal antibody (MoAb) B72.3 is reactive with a variety of carcinomas such as colorectal and ovarian carcinoma and not reactive with a range of normal tissues in adults. Twelve patients, ranging in age from 16 to 63 years, with metastatic colorectal or appendiceal carcinoma were studied by means of radioimmunoscintigraphy after injection of 5-10 mCi (185-370 MBq) of iodine-131 labeled B72.3 immunoglobulin G (IgG). Eight of the 12 patients had positive scans. In three of these patients the MoAb scan depicted tumors that were not found by other means. Positive scans had excellent correlation with surgical findings in seven patients and caused underestimation of the extent of disease in one patient. In one patient the scan was technically inadequate and could not be evaluated. In three patients the scan was negative. No adverse reactions were associated with the infusions. PMID- 3347743 TI - Percutaneous gastrostomy. PMID- 3347744 TI - Anastomotic strictures of the upper gastrointestinal tract: results of balloon dilation. AB - Enteroenteric anastomotic strictures of the upper gastrointestinal tract are common and require treatment if significant obstruction occurs. The authors performed 44 fluoroscopically guided balloon dilations in 19 patients with symptomatic anastomotic strictures. The anastomoses were esophagoesophageal (n = 5), esophagogastric (n = 8), esophagoileocolonic (n = 4), and gastrojejunal (n = 2). Nine patients required only one balloon dilation for stricture lysis and relief of clinical symptoms. Recurrent symptoms developed in the remaining ten patients, who required two to eight dilations. Radiographically, stenoses made up 40%-90% of the anastomotic lumen before dilation (mean, 72%). Complete resolution of the stricture was achieved during the procedure in 24 instances. Residual stenosis in 18 instances varied from 7% to 45% (mean, 21%). Two complications, a mucosal tear and a perforation, were immediately recognized and successfully treated non-operatively. The authors conclude that fluoroscopically guided balloon dilation has an important role in the treatment of anastomotic strictures of the upper gastrointestinal tract. PMID- 3347745 TI - Percutaneous drainage of mediastinal pseudocysts. AB - Percutaneous catheter drainage of a mediastinal pseudocyst was performed in two patients. Access was gained through computed tomography (CT)-guided puncture of the abdominal portion of the pseudocyst in one patient, and a transhepatic subxiphoid approach was used in the other. Guide wires and catheters were advanced into the mediastinal pseudocysts under CT control. Drainage was technically successful in both patients, with no procedure-related complications. Percutaneous drainage is an alternative to the surgical treatment of symptomatic and nonresolving mediastinal pseudocysts, provided that a safe access route can be found. PMID- 3347746 TI - Neurologic complications of pelvic intraarterial chemoembolization performed with collagen material and cisplatin. AB - In three patients neurologic complications developed after chemoembolization procedures were performed with cisplatin and a new collagen material. Three patients with dominant unilateral stage III cervical carcinoma were entered into an investigative protocol attempting to control regional disease and pain with chemoembolization. All three patients had previously undergone surgery, radiation therapy, and intraarterial chemoembolization or chemoinfusion. Each case was complicated by neurologic deficits. A collagen material was administered that acts at a precapillary level and reduces the likelihood of collateral flow. The size of the material enables it to embolize the small feeding vessels of the spinal cord and peripheral nerves. The patients in this study also had predisposing factors to neurologic sequelae including the previous therapy and the contributing neurotoxicity of cisplatin. The neurologic complications in these patients are not easily explained by knowledge of the neurovascular anatomy. Even with meticulous technique, intraarterial chemoembolization of the pelvis with cisplatin and collagen can be complicated by serious neurologic deficits. PMID- 3347747 TI - Long-term occlusion of the porcine cystic duct by means of endoluminal radio frequency electrocoagulation. AB - Recurrent cholelithiasis must be expected after gallstone removal without cholecystectomy. Chemical gallbladder ablation may offer prevention but requires preliminary cystic duct occlusion. Radio-frequency (RF) electrocoagulation of the cystic duct was performed in 15 pigs to induce occlusion by a controlled thermal epithelial injury. A flexible coagulation catheter was placed into the cystic duct lumen under fluoroscopic control by means of either subhepatic cholecystostomy or direct, percutaneous transhepatic gallbladder puncture. Complete cystic duct occlusion was proved in 14 animals. Follow-up ranged from 1 to 17 weeks (mean, 11 weeks). Histologically, the RF technique induced an intense chronic inflammatory and fibroblastic reaction, which eventually obliterated the coagulated cystic duct segments. There was no epithelial regeneration or recanalization of the fibrotic cystic duct segments. The adjacent structures, particularly the cystic artery, were intact in all specimens. PMID- 3347748 TI - Balloon techniques for percutaneous gastrostomy in a patient with partial gastrectomy. AB - Intragastric balloon techniques were used to achieve direct gastric distention and efferent loop obstruction in order to perform percutaneous gastrostomy on two occasions in a patient with a partial gastrectomy and Billroth II anastomosis. Previous attempts at percutaneous endoscopic gastrostomy and conventional radiologic percutaneous gastrostomy had been unsuccessful. Although a history of partial gastrectomy has been considered an impediment to both percutaneous gastrostomy and percutaneous endoscopic gastrostomy, this experience demonstrates that percutaneous gastrostomy can be performed safely in this setting with balloon assistance. PMID- 3347749 TI - The state of radiographic technique in the examination of the colon: a survey in 1987. AB - Results of an extensive multiple-choice questionnaire sent to 175 leading medical centers in the world were analyzed and compared with those of a similar survey from 1976. One hundred sixty-two (93%) responses were received. Both single- and double-contrast enema procedures are still employed, but the use of the double contrast technique has markedly increased. Preparation of the colon is even more meticulous than in 1976 and is equal for both techniques. Pharmacologic aids are used more often but preparatory enemas less frequently than in 1976. The use of fluoroscopic equipment has not significantly changed. The decision on the appropriate sequence for the barium enema examination and colonoscopy is based on the individual clinical problem in the majority of cases, and the time interval between the barium enema examination and lower endoscopy with or without biopsy is significantly shorter than in 1976. The use of computed tomography and magnetic resonance imaging has increased since 1976, but angiography is used less often and mostly for unknown causes of bleeding and to stop bleeding. PMID- 3347750 TI - Breast cancer imaging with In-111 human IgM monoclonal antibodies: preliminary studies. AB - Detection of specific tumor sites was studied with scintigraphy and radiolabeled human IgM monoclonal antibodies (MoAbs). Ten patients with metastatic breast cancer received an infusion of one of three indium-111-labeled anti-breast carcinoma MoAbs. The time of infusion ranged from 30 minutes to 2 hours. Three patients received YBB-190 at total doses of 2, 4.25, or 11 mg, four patients received YBM-209 at total doses of 1 mg (n = 1) or 20 mg (n = 3), and three patients each received 22 mg of YBY-088. Imaging was performed immediately after infusion and at 4, 24, 48, 72, 120, and 144 hours. Many presumed sites of metastatic disease were imaged in three of the four patients who received 20 mg of YBM-209 and in two of the three patients who received YBY-088. Tumor was not detected in any of the patients who received YBB-190, in the patient who received a 1-mg dose of YBM-209, or in the patient who received YBY-088 and in whom a biopsy of tumor tissue failed to demonstrate target antigen. The authors conclude that In-111-labeled human IgM MoAbs can target human breast cancer, but antigen expression and antibody dose determine successful immunoscintigraphy. PMID- 3347751 TI - Classification of parenchymal injuries of the lung. AB - Pulmonary contusion, implying interstitial and alveolar injury without significant laceration, has been accepted as the primary lung injury in nonpenetrating chest trauma. Computed tomographic (CT) findings were compared with those of chest radiography in 85 consecutive patients with chest trauma in which there was a pulmonary radiodensity consistent with pulmonary contusion or patients with a history of severe chest trauma with normal parenchyma despite rib fractures, hemothorax, pneumothorax, or widened mediastinum. CT was found to be more sensitive than radiography in that 151 abnormalities (excluding rib fractures) were demonstrated on radiographs versus 423 abnormalities on CT scans, and 99 lacerations were seen on CT scans versus five on radiographs. Pulmonary lacerations were classified into four types on the basis of CT findings and mechanism of injury: compression rupture, compression shear, rib penetration, and adhesion tears. In these cases, pulmonary laceration was shown to be an integral component of the mechanism of injury in pulmonary contusion, pulmonary hematoma, pulmonary cyst or pneumatocele, or cavitation in pulmonary contusion. PMID- 3347752 TI - Pneumothorax and other lung diseases: effect of altered resolution and edge enhancement on diagnosis with digitized radiographs. AB - Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm). PMID- 3347754 TI - Benign esophagorespiratory fistulas in adults. AB - Four benign esophagorespiratory fistulas, three secondary to granulomatous disease and one presumed to be congenital, have been diagnosed in adults at the authors' institution in the past year. The patients had symptoms of chronic or recurrent pulmonary infections, and two experienced coughing after swallowing. Chest radiographs demonstrated refractory consolidation, with or without cavitation and frequently accompanied by an air-distended esophagus. Barium studies were diagnostic. All patients responded well to antibiotic and surgical therapy. PMID- 3347753 TI - Internal mammary lymphadenopathy in breast carcinoma: CT appraisal of anatomic distribution. AB - Internal mammary lymph nodes are an important site of occult metastasis in clinically operable and recurrent breast carcinoma. Anatomic distribution of enlarged internal mammary nodes in patients with breast cancer was analyzed in a review of thoracic computed tomographic studies of 219 women with operable, advanced, or recurrent cancer. Enlarged nodes were observed in 45 patients (20.5%), 32 with unilateral and 13 with bilateral involvement. Mean nodal diameter was 1.95 cm (0.6-6.0 cm). Lymphadenopathy was limited to one anterior intercostal space in 43%, two spaces in 26%, three spaces in 22%, and four spaces in 9%. Solitary or dominant nodal enlargement was centered at the first space in 14%, second space in 60%, and third space in 26%. Isolated lymphadenopathy in the fourth or fifth spaces was not observed. Metastases to internal mammary nodes frequently occur at multiple levels and are most common in the second and third spaces. This finding concurs with current surgical practice when internal mammary nodes are sampled. PMID- 3347755 TI - When nurses must question doctors' orders. PMID- 3347756 TI - The nurse's right of self-defense. Case in point: Theodore v. Dept. of Health & Human Res. (515 So. 2d 454--LA La. App. 1 Cir. 1987). PMID- 3347757 TI - Legal case briefs for nurses. OH.: nurse education: student terminated; MN.: respondeat superior: limitations issue. PMID- 3347758 TI - CRNA negligent: aspiration causes death. Case in point: Pierre v. Lallie Kemp Chariy Hosp. (515 So. 2d 614--LA (La. App. 1 Cir. 1987). PMID- 3347759 TI - [Freud and Jung. Dynamics of their relationship and termination of its significance for the psychoanalytic movement and institutionalized psychoanalysis]. PMID- 3347760 TI - [100 years of psychoanalysis: the beginning of maturity]. PMID- 3347761 TI - The convergence between in-labor report and postpartum recall of parturition pain. AB - This non-experimental study was designed to investigate the congruence between in labor report and postpartum recall of labor pain as measured by the McGill Pain Questionnaire (MPQ). Fifty married parturients, ages 19 to 39 at term with a normal pregnancy, served as subjects. Analysis of variance showed that postpartum report of labor pain on the Present Pain Intensity scale of the MPQ was not consistently congruent with pain reported during labor. In contrast, the Pain Rating Index of the MPQ provided postpartum data that was congruent with the in labor report. Significant interaction effects, however, suggested that postpartially the women tended to devaluate the pain of early labor and inflate the pain of transitional labor when compared to their in-labor report. Theoretical and practical implications of the results for the measurement of labor pain are discussed. PMID- 3347762 TI - Preparing children for radiologic procedures: contingent versus noncontingent instruction. AB - The purpose of this study was to examine the effects of choice of information in preprocedural instruction on children's responses to select radiologic procedures. Sixty-one children were randomly assigned to either the contingent (n = 31) or noncontingent (n = 30) instruction group. Contingent instruction provided information in response to children's questions and requests. Noncontingent instruction provided children information based on recommendations from the literature and clinical practice. Dependent variables were measured using the Manifest Upset Scale, Cooperation Scale, search for information protocol, and self-report of distress. Contingent instruction was associated with less search for information. Prior to painful instrusive radiologic procedures, a choice of information may not support information-seeking, a strategy for adaptation. PMID- 3347763 TI - Maternally administered tactile, auditory, visual, and vestibular stimulation: relationship to later interactions between mothers and premature infants. AB - Thirty-three mother-infant pairs were randomly assigned to one of three groups: control, talking, or interactive (RISS). The later treatment included massage, talking, eye contact and rocking. The intervention (RISS) was administered to determine whether mothers and their preterm infants who actively interacted with each other would differ on later maternal and infant behaviors. The talking and RISS treatments were administered at specified time intervals 24 hours after delivery. Prior to hospital discharge, mother-infant interaction was assessed during a feeding. Significant differences were identified among the three groups for maternal (p less than .03) and infant (p less than .05) behaviors. These results suggest that active maternal interaction with the premature infant may enhance specific components of mother-infant interaction. PMID- 3347764 TI - Ethnic differences in knowledge of sexually transmitted disease in North American black and Mexican-American migrant farmworkers. PMID- 3347766 TI - [Prevalence of infection in the cervix with human papilloma virus in a population of prostitutes of the city of Panama]. PMID- 3347765 TI - [Cutaneous leishmaniasis caused by Leishmania mexicana amazonensis in Panama]. PMID- 3347767 TI - [Inguinal herniorrhaphy carried out under local anesthesia]. PMID- 3347768 TI - [Activity of the influenza virus in the metropolitan region of the city of Panama, 1976-1986]. PMID- 3347769 TI - [Biostatistical methods in scientific research: prospective logistic models in retrospective studies]. PMID- 3347770 TI - [Multiple brain abscesses caused by Toxoplasma gondii in a patient with acquired immunodeficiency syndrome. First case described in Panama]. PMID- 3347771 TI - [Primary malignant hemangioendothelioma of the skull]. PMID- 3347773 TI - [Cavernous hemangioma of the ethmoid bone]. PMID- 3347772 TI - [Aztreonam in infections caused by gram-negative aerobic bacilli]. PMID- 3347774 TI - [Occurrence of antigen S of hepatitis B in donors to the blood bank of Saint Thomas Hospital]. PMID- 3347775 TI - [Corticoid activity of chuifong toukuwan pills and detection of indomethacin]. PMID- 3347776 TI - [Neurocysticercosis in Panama]. PMID- 3347777 TI - [Clinico-radiologic correlations in 2 cases of immunoproliferative disease of the small intestine]. PMID- 3347778 TI - [Treatment of diaphyseal pseudoarthrosis with transosseous osteosynthesis by the Ilizarov method. Radiographic signs of reparative osteogenesis]. AB - The main phases of ossification are shown-based on the results achieved by re examining the X-ray pictures of 14 patients affected by tubular bones pseudoarthrosis treated with Ilizarov's closed compression-distraction osteosynthesis. The roentgen signs in particular are examined which are considered as expressive of positive evolution of the pseudoarthrosis. An outline of X-ray evolution of nonunions is also proposed, referring to the peculiar biological characters of ossification under compression-distraction stimulation. PMID- 3347780 TI - [Glossary of thoracic radiography]. PMID- 3347779 TI - [Uriniferous perirenal pseudocysts. Presentation of a case studied also with computerized tomography]. PMID- 3347781 TI - [Traumatic lesions of the brachial plexus. Evaluation of 144 cases studied using direct cervical myelography and non-ionic contrast media]. AB - The authors report their experience in 144 patients with traumatic brachial plexus injury who underwent Direct Cervical Myelography (DCM). Sometimes the diagnostic investigation was completed by CT. Various myelographic patterns are described: pseudomeningocele, missing sheet of the root, scarring lesions. In 9 cases only, myelography was not sufficient to provide a complete diagnosis. The examination showed all plexus roots lacerated in 14 patients, a monoradicular lesion in 75 cases, and no lesion in 26 cases. Twenty-one out of the 26 negative cases were confirmed during surgery, while in 2 patients an intraspinal injury was found, which had not been detected due to the presence of scars. Scars often compress healthy roots, and may mask intraspinal injuries. In such cases, and when the spinal cord stretches towards the side of the lesion, Myelo-CT can be useful. DCM proved to be an extremely sensitive and specific method, which can be used as a first-choice radiological procedure in the study of traumatic injuries of the brachial plexus. PMID- 3347782 TI - [Comparing computerized tomography and magnetic resonance in the study of articular pathology of the knee]. AB - The authors present a comparison between the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in the articular pathologies of the knee. CT and MRI were performed in 30 patients who subsequently underwent surgery. CT and MRI results were compared on three bases: technique, definition of normal anatomy, and diagnostic accuracy. CT allowed a standardization of the technique, while MRI was superior in defining normal anatomy--especially in the study of capsulo-ligamentous structures. In all cases the use of both CT and MRI allowed a correct diagnosis, showing the site, extent and gravity of the lesion. CT proved to be superior to MRI in 4 cases, while MRI corrected CT diagnosis in 11 cases; in 15 patients both techniques had the same diagnostic accuracy. Meniscal tears were better identified by CT, while MRI was superior in the detection of ligamentous lesions and in the characterization of PVNS and tendinitis of the patellar tendon. In conclusion, MRI should be performed in selected cases only, or when CT cannot be trusted; on the other hand, it might also be used as a first-choice diagnostic procedure for synovial pathologies and acute lesions of the anterior cruciate ligament. PMID- 3347783 TI - [Pulmonary edema in renal insufficiency]. AB - Forty-nine cases of pulmonary edema in nephropatic patients were studied. The most frequent radiologic findings are discussed. The unreliability of a precise differentiation between "cardiac" and "renal" patterns of pulmonary edema in nephropatic patients is emphasized. PMID- 3347784 TI - [Dynamics of food transit in gastrectomized patients with and without dumping syndrome studied with the gamma camera and a marked meal]. AB - Scintigraphy was performed on a group of patients following the administration of a solid radiolabelled meal. As a tracer, human albumin microspheres were used with 99mTc, mixed with fresh scrambled eggs, eaten as a sandwich in two slices of white bread. The analysis of transit and emptying-rate of the radiolabelled meal in the gastric or derivative loop areas was performed by means of a medium field (300 mm) gamma camera interfaced with a digital computer; the data were collected at 15" frames for 90'-120'. Twenty-nine patients were examined who had undergone sub-total gastrectomy: 11 of them were "dumpers" and 18 "non-dumpers"; moreover, 9 volunteers without any history of gastrointestinal diseases and 11 patients with different gastric disorders were checked. In the first group of gastrectomized patients the half-emptying time (T50) was significantly shorter than in the 11 people being checked (Md = 27.5 +/- 10.8 versus 69.6 +/- 19 minutes); in "non-dumpers" T50 was even shorter (Md = 24.2 +/- 13 min). There was no significant statistical difference between the two classes of gastroresected patients in both T50 and emptying-rate of the radioactive solid food, which excludes the accelerated transit as a factor in the functional post-prandial symptoms of the dumping syndrome. On the contrary, the dynamic selective analysis of the radiolabelled food transit through derivative afferent and efferent loops showed different patterns in the two groups of gastroresected patients: the progression of the propulsive wave was very irregular and constantly hyperperistaltic only in the dumpers. PMID- 3347785 TI - [Syringocele or cystic diagnosis of Cowper's gland ducts]. AB - Cystic dilatation of bulbo-urethral gland ducts (Cowper's syringocele) is an uncommon abnormality, frequently asymptomatic, showing various radiographic patterns. The lesion is more commonly seen in children, but it may be found in adults too, and may cause dysuria, pollakiuria, stranguria and posturinary dribbling. Fourteen patients with syringocele were observed: 6 of them were asymptomatic, while in 8 the most common symptoms were posturinary dribbling and stranguria. X-ray examination showed 7 cases of perforated syringocele, 4 cases of ruptured syringocele, 2 cases of simple syringocele and 1 case of imperforate syringocele. Various theories are reported to explain how the lesion forms and the differences are analyzed which characterize different kinds of urethral lesions. PMID- 3347787 TI - [Scintigraphy of the bone marrow for the evaluation of injuries caused by antiblastic agents]. AB - For various reasons the well-known myelopoietic damage caused by cancer chemotherapy is not easy to quantify by means of usual diagnostic procedures. The bone marrow scan with a Tc 99m-nanocolloid rapidly cleared by the phagocytic action of the RES, which has a topographic extension similar to red marrow, has been used for many years to evaluate the inflammatory and neoplastic diseases, both localized and diffuse. Such examination was thus performed in patients undergoing cytostatic therapy, either to follow-up metastatic lesions or to evaluate a tissue damage due to different drugs. The BMS is easily performed and has no side-effects. It consists of a dynamic and a static part. Moreover, it helped pointing out important diagnostic data, such as the reduction of the sacroiliac uptake index below the normal values (3.7) in 33 out of 57 cases, and an abnormal distribution of nanocolloid in the skeleton (Munz's classification, 1983) in 37 out of 69 cases, higher in more myelotoxic cytostatics, which could be detected even after a few months. PMID- 3347786 TI - [Pulmonary scintigraphy with radioaerosol in idiopathic scoliosis]. AB - The study of respiratory function is of key importance for the clinical evaluation of patients with idiopathic scoliosis. Such study has been traditionally based on classical pulmonary function tests and arterial blood gas analysis. However, neither procedure gives any information on the topographical distribution of abnormalities, and both might be suboptimal as far as sensitivity is concerned. The preliminary results obtained with radioaerosol lung scintigraphy in 11 patients with scoliosis are here presented. They lead to the conclusion that radioaerosol lung scintigraphy, besides being an useful adjunct to more traditional diagnostic procedures, can yield unique information on the localization of convective ventilation derangements induced by the dynamic abnormalities of the rib cage. PMID- 3347788 TI - [Role of computerized tomography in the definition of the area to be irradiated in bone metastases]. AB - In the Department of Radiology of the Catholic University S. Cuore in Rome, a review was made of 342 CT examinations with a view towards optimizing the therapeutic planning in patients affected by bone metastases. All patients were submitted to radiological positioning and then to CT evaluation in order to assess the volume to be treated. In 224 cases it was not necessary to perform wide CT examination (3-5 standard tomograms being enough, 2 of which at the superior and inferior margins of the planned field). In the second group of 118 patients it was necessary to perform CT (serial axial scans)--increasing by 1-1.5 cm--up to the superior and inferior margins of the lesion. The existence of 2 types of lesions was confirmed: those involving mainly bony structures and those infiltrating the soft tissues. CT evaluation allowed the definition of the target volume to the real extension of the lesion in 14% of the whole of cases, while in the group of 118 cases studied more thoroughly, the percentage went up to 41%. CT allowed a better assessment of secondary bone lesions, especially in kidney and lung neoplasms. The metastatic site that required a more frequent modification of the irradiation field was the chest. To conclude, the authors emphasize the importance of CT in assessing the target volume, especially in those cases in which conventional radiology does not allow a reliable evaluation of the lesion, possibly compromising the local monitoring of the disease. PMID- 3347790 TI - [Effect of various roentgen contrast media on pancreatic and liver enzymes in ERCP]. PMID- 3347789 TI - [Role of magnetic resonance in the staging and post-chemotherapeutic follow-up of malignant maxillo-facial tumors]. AB - Ten patients with squamous cell carcinomas located in the maxillo-facial region were studied. In all cases the staging by Computed Tomography (CT) and Magnetic Resonance (MRI) revealed metastatic lesions in stage T3-T4. All patients underwent polichemotherapy before surgery. MRI proved to be more accurate in the staging of tumors in 3 cases only, while in 7 cases both techniques showed the same diagnostic accuracy. In the follow-up, MRI allowed the evaluation of the effect of chemotherapy on the carcinomas: it demonstrated the regression and necrosis of 9 tumors out of 10 (the patients could undergo surgery), and the progression of the tumor in 1 case. The study of bioptic specimens demonstrated the lack of correlation between histological grading of the tumors with MRI signal intensity and T1, T2 relaxation time, as measured by spectroscopy. PMID- 3347791 TI - [Ulcers and hiatal hernia. Apropos of 19 endoscopic case reports]. PMID- 3347792 TI - [Bougienage as a therapeutic measure]. PMID- 3347793 TI - [Suspicion of Cushing's syndrome--what to do?]. PMID- 3347794 TI - [Endocrine hypertension: primary aldosteronism and pheochromocytoma]. PMID- 3347795 TI - [Weakness, chest pain, hypertension, hirsutism]. PMID- 3347796 TI - [Acute cerebral vascular accidents. General results of the first 1000 cases in the Lausanne neurology registry]. PMID- 3347798 TI - [Sedation]. PMID- 3347797 TI - [Asymmetrical cerebral lesions and subcortical aphasia in carbon monoxide poisoning]. PMID- 3347799 TI - [Plastic reconstruction of the breast]. PMID- 3347800 TI - [Neuro-linguistic programming, a new approach in the physician-patient communication]. PMID- 3347801 TI - [The aged: a phase of human development: sexual aspects]. PMID- 3347802 TI - [Child, school, parents and I: a systemic approach to the description of scholastic difficulties]. PMID- 3347804 TI - [Health policy]. PMID- 3347803 TI - [Address delivered at the general meeting of the Vaud Medical Society on 26 November 1987]. PMID- 3347805 TI - [Magnetic resonance imaging in horizontal oculomotor paralysis caused by infarction]. AB - Four patients with focal brainstem ischemic strokes and various types of horizontal oculomotor disturbances have been studied clinically and radiologically. One had a six nerve palsy, one a unilateral internuclear ophthalmoplegia, one a Fisher's one-and-a-half syndrome, and one a paramedian pontine reticular formation syndrome with a sixth nerve palsy. In all patients a C.T. Scan and a Magnetic Resonance Imaging (MRI) were obtained. The MRI study was performed on a CGR Magniscan 5000 with a superconducting magnet of 0.5 Tesla. In all patients a hypersignal in T2 weighted images was shown and corresponded to the brainstem infarct. MRI allowed accurate delineation of the lesion and clinico radiologic correlations in three patients. But the low specificity of MRI does not permit to distinguish edema from necrosis, gliosis or demyelination in a region with a pathological MRI signal. In one patient this low specificity and perhaps partial volume effects decreased the accuracy of the clinico-topographic correlation. PMID- 3347806 TI - [Isolated cervical intramedullary metastasis from breast cancer. Value of magnetic resonance imaging]. AB - A metastasis from a breast carcinoma developed in the cervical cord. The localisation and nature of the lesion were easily diagnosed by a contrast MRI study with Gadolinium DTPA. PMID- 3347807 TI - [2 families with benign myopathy predominantly on the limb girdle with dominant autosomal heredity]. AB - Very few authenticated cases of benign muscular dystrophy affecting mainly the girdles and of dominant autosomal inheritance have been documented. Two families were seen with this type of transmission, and certain common characteristics noted: proximal weakness and amyotrophy, frequency of muscle contractures, mainly distal, true calf hypertrophy, slow progression and benign nature and finally a fairly uniform semiology in the same family, an atypical finding in dominant autosomal hereditary disease. PMID- 3347808 TI - [Acute idiopathic orbital myositis]. AB - Idiopathic acute orbital myositis is a subgroup of inflammatory orbital pseudotumor. The case of a 35 year-old woman who suffered a left ocular pain with eyelid swelling, conjunctival hyperemia and limitation of abduction of the left eye is reported. CT showed an enlargement of the left medial rectus muscle enhanced with contrast. The pathogenesis remained obscure. The evolution was favourable with corticosteroids. PMID- 3347809 TI - [Clinico-pathological conference at the Salpetriere. January 1987. A confusional state with progressive development]. PMID- 3347810 TI - International Symposium on New Quinolones. Geneva, Switzerland, July 17-19, 1986. Proceedings. PMID- 3347812 TI - [Meconium fluid. Significance and management]. AB - The authors have tried to determine the significance of meconial fluid by studying 3 groups: a first group (MF) representing the meconial fluid observed at he beginning, the second group where the meconial fluid was observed secondarily (SMF) and a third group which is the reference group (RG). The presence of meconial fluid is an ominous sign and an element of prognosis of fetal distress. Meconial fluid at the beginning may be present physiologically, but there are authentic pathological cases with a markedly decreased residual Apgar at 5 minutes. In addition, the perinatal mortality is 4 times higher. In the group with secondary meconial fluid, it is more of an obstetrical emergency. Distress occurs on a healthy fetus along with labor. The signs are occurring with abnormalities of the fetal heart rhythm which do not aggravate the prognosis. These data are confirmed with the study of the pH at the cord. The risk of meconial fluid is inhalation and its complications. The authors conclude by insisting of the need for nasopharyngeal aspirations soon as the fetal head is delivered. PMID- 3347811 TI - Comparative antibacterial activity of new quinolone-carboxylic acid derivatives. AB - In vitro and in vivo antibacterial activities of new quinolone-carboxylic acid derivatives are described. A compilation of MICs of nalidixic acid, pipemidic acid, and seven new quinolones (norfloxacin, ofloxacin, enoxacin, ciprofloxacin, pefloxacin, NY-198, and AM-833) is presented. The new quinolones exhibit potent antibacterial activity against the enteric gram-negative bacteria. These compounds also are active against Pseudomonas aeruginosa and gram-positive bacteria. MICs of these agents for Bacteroides fragilis are higher. Excellent bactericidal activity of new quinolones, the result of their strongly inhibitory activity against bacterial DNA gyrase, was found to be characteristic. The bioavailabilities of the new quinolones are discussed from the standpoint of their physicochemical properties. The quinolone compounds are classified roughly into three groups: lipophilic, hydrophilic, and intermediate agents. Ciprofloxacin, norfloxacin, and enoxacin belong to the hydrophilic group. The intermediate group, which includes ofloxacin, AM-833, NY-198, and pefloxacin, achieved higher serum levels after oral administration. Thus, the antibacterial activities of these agents in vivo are thought to reflect their antibacterial activities in vitro and their bioavailability. PMID- 3347813 TI - [Intra-amniotic transmission of the human voice]. AB - New acoustic measurements in amniotic environment permit to specify the conditions of transmission of human voices: voices emerge, incompletely covered by a low background noise, but however higher pitched near the placenta. The recognition of phonemes in utero is rather weak, approximately 30 per cent and appreciably identical for all voices and different mode of emission. Therefore this type of recognition is likely to play a minor role: the voices are evenly toneless by lack of high-pitch, and there is no obvious superiority of the intelligibility of direct maternal voice. The recognition of vowels by their second forming, as well as the emergence (demonstrated with special microphones) of impulse noises with very high-pitch components and of synthetic speech, confirm the possibility of transmission of frequencies exceeding 1,500 Hz to the intra-amniotic environment. On the contrary, melody recognition is excellent: probably major role of this factor. The loudness of the maternal voice transmitted to the uterus exceeds markedly that of outside voices, and this voice is certainly accessible to the fetus, most of the time. The demonstration of the transmission to the amniotic fluid of noises and voices enables to consider the possibility of perception. PMID- 3347814 TI - The media and nursing image. PMID- 3347815 TI - Giving support. PMID- 3347816 TI - Nursing research: a dialogue begins. PMID- 3347817 TI - Workplace work-up: assessing working conditions. PMID- 3347818 TI - [Chronic obstructive bronchopathy in children]. PMID- 3347819 TI - [Current aspects of bronchiectasis in children]. PMID- 3347820 TI - [Inhalation pathologies]. PMID- 3347821 TI - Health for all by the year 2000--National Finnish Impact on the Global Development Programme. PMID- 3347822 TI - Chronic otitis media and sequelae in the population of Greenland. AB - It is generally recognized that chronic otitis media and sequelae of this disease are frequently encountered among the native population of Greenland, but the prevalence of chronic otitis in Greenland has not previously been systematically traced. Treatment for this disease has improved and we expect an increased demand for treatment of this disease among Greenland natives. To evaluate the need of treatment the prevalence of chronic otitis media in two large Greenland towns was assessed. The study population included 303 persons aged 11-20 years and 305 aged 41-50 years. Medical histories were recorded and objective examinations were performed using e.g. oto-microscopy. Among the young participants, 8% had chronic suppurative otitis and 14% sequelae of chronic otitis media. Among the older participants, 2% had suppurative otitis and 13% sequelae of chronic otitis. It is estimated, using Scandinavian criteria, that 8.6% of the participants would have benefitted from an ear operation either to stop otorrhea and/or to improve the hearing. The launching of an oto-surgical effort in Greenland is considered justifiable on the grounds of the importance of hearing to communication and the isolation in point of the native Greenland population. PMID- 3347823 TI - One-year incidence of occupational injuries among teenagers in a Swedish rural municipality. AB - The aim of this study was to investigate occupational injuries among teenagers in a defined population and geographical area with regard to incidence and severity and to compare our registration system with that of the Swedish Occupational Injury Information System. All occupational accidents in the age group 15-19 years were registered at public health centres. We found a higher incidence compared to school accidents in the same age group as well as in relation to occupational accidents in the older population. Part-time work, lack of experience, temporary employment, unskilled work, and age-specific behavioural patterns are factors that might explain the higher incidence rate. The highest rates were found in service, military and unspecified occupations. Only 25% of the work-related accidents in our study were registered by the Swedish Occupational Injury System (ISA). It seems possible to reduce the number of accidents through the instigation of fairly simple measures. The coverage of the registration by the ISA seems to be incomplete. PMID- 3347824 TI - The working capacity of the alcohol abuser. Prognostic multiple regression analyses. AB - Thirty-four alcohol abusers treated at various rehabilitational locations in Sweden were the subjects of an extensive and interdisciplinary study. Thereafter, the working capacity of each subject was followed over a two-year period. Twelve individuals regained capacity for work, either partially or completely. Thirteen subjects were sick-listed or remained unemployed. The remaining 9 abusers were quickly and unexpectedly pensioned. In order to predict the rehabilitational outcome from the interdisciplinary findings at the onset of the time period, stepwise multiple regression analyses were performed. Those who felt less lonely and had no drinking buddies appeared most likely to be rehabilitated vocationally. This core combination of characteristics accounted for about one third of the variability in the outcome criterion, either trichotomized or dichotomized. Rehabilitational success could be even more strongly predicted by the appearance of such features as less prolonged abuse, social introversion (not cohabiting, reserved attitudes and having only a few friends), orientation to the future and a history of psychiatric care. An elevated level of plasma albumin and a decreased plasma-IgA value raised additionally the multiple correlation coefficient. PMID- 3347825 TI - Contributions of social medicine and systems analysis to formulating objectives for a community-based cancer prevention programme. AB - In the part of Stockholm Cancer Prevention Programme, that is focussing on diet and cancer, the contribution of social medicine has been based on its concern for the relationships between individuals, populations, the environment and the socio political structure. This has led to the choice of the community intervention approach, based on geographically defined populations, and involving the participation of organisations already active within the relevant areas. The contribution of systems analysis has been based on its concern for explicit models of the processes of cause and effect that lead from intervention to outcome, as a basis for debate and common understanding among the various participants. The combination of the two approaches has helped to clarify the objectives and has shaped the planned pattern of intervention. PMID- 3347826 TI - Regret among 547 Danish sterilized women. AB - To help identify potential regretters of female sterilization, the women sterilized at Frederiksborg County Hospital, Horsholm, Denmark, from 1978 through 1982 were contacted by questionnaires, and their medical records were reviewed. Ninety-two per cent (547/594) responded. The median observation time was 50 months. Five per cent of the women (n = 28) regretted the sterilization. The risk of regretting the sterilization was significantly increased among women who at sterilization experienced marital disharmony (12.5% regretted), had a child less than one year old (14.7% regretted), had the sterilization performed in connection with another surgical procedure (16.1% regretted), were outside the social groupings (17.0% regretted), or had no paid work (10.0% regretted). No association between number of children at the time of sterilization, prior number of contraceptives used, abortion at sterilization, and later regret was found. Twenty-five per cent of the regretters had had psychiatric problems prior to the sterilization. The regretters were sterilized shortly after their request (median 1 month) compared to 3 months among non-regretters. The main reason for regret of sterilization was the desire for more children, independent of a change in marital status. Sequelae to the sterilization was a common complaint. Refertilization was requested by 1% of the sterilized women. The study suggests that the psychosocial situation should be carefully evaluated in women requesting sterilization. A time lag from request to the sterilization should be mandatory and a thorough pre-sterilization counseling including information about possible sequelae and alternative contraceptives should be given. PMID- 3347827 TI - Comparison between data obtained through questionnaires and interviews: life style habits of pregnant women. AB - A random sample of pregnant women in the cities of Odense and Aalborg, Denmark, was taken as a part of a quasi-experimental study. The time period of the study was from October 1984 to March 1985. Out of 175 randomly selected pregnant women, 146 filled out the questionnaire in the 36th week of their pregnancy. The questionnaire was concerned with eating, smoking, and drinking habits before and during their pregnancy. These 146 pregnant women participated in an interview 3 weeks later where some of the same questions on the questionnaire were asked by the interviewer. In spite of the rather short interval between the two data collections, there were some differences in the answers given at the individual level. This is especially true for eating habits and estimated average drinking habits during pregnancy. No tendency was observed for a more frequent recalling of "less socially acceptable norms" in the questionnaire method of obtaining information. Lack of knowledge of the "true" classification is probably the main reason for the lack of stability in the answers given. This leads to some unavoidable misclassification in studies on self-reporting life style habits among pregnant women. PMID- 3347828 TI - The period prevalence of musculoskeletal complaints among Swedish professional drivers. AB - The aim of the investigation was to survey the period prevalence of musculoskeletal complaints among Swedish professional drivers. 460 out of 570 male drivers answered a postal inquiry. The period prevalence of musculoskeletal complaints was highest for the low back, the shoulders, the knees and the neck, in that order. For some parts of the musculoskeletal system the period prevalence of complaints tended to increase with age. A subdivision of the examined group of drivers according to task revealed--after standardizing for age (SRR)--different relative risk of complaints in various anatomical regions of the body. The interaction among some variables was studied by means of Automatic Interaction Detection Analysis. The analysis showed that the variables age and task reduced the variance of the period prevalence of musculoskeletal complaints most. PMID- 3347829 TI - Mentally ill mothers and their children. A controlled study of social welfare utilization. AB - 177 cases of parapartum mental illness and 173 matched obstetric controls were studied retrospectively from the perspective of the social welfare services (SWS). Data covering five years before the index partus until five to seven years thereafter, were studied. Parapartum mentally ill women were known to the SWS to a much greater extent (75%) than their matched controls (33%). They also presented more severe environmental problems than their matched controls. Within the index sample the largest number of adverse factors known to the SWS was found in the addicts and NTI (neuroses and temporary insufficiencies) groups. The dysfunction in the families appeared to be constant throughout the observation period. A large proportion of the index children (32%) had been placed in foster care or adopted. When the index women had applied to the SWS during the first postpartum year the social workers were informed of the fact that she had contacted a psychiatric department in 8 out of 10 cases. However, only in half of these cases had regular collaboration taken place. Collaboration was far more frequent when the mother suffered from severe mental illness than when she was suffering from a less severe mental disturbance. PMID- 3347830 TI - Explaining regional variations in health care. PMID- 3347831 TI - [Objective assessment of ovarian function in freshly calved cattle]. PMID- 3347832 TI - [Comparative histomorphometric studies of the bones of healthy fattening swine and those with osteochondrosis]. PMID- 3347833 TI - Creative deception. PMID- 3347834 TI - The IPPNW: a single-issue organization. PMID- 3347835 TI - Animal rights. PMID- 3347836 TI - The (private) university of NIH? PMID- 3347837 TI - Human experiment roils French medicine. PMID- 3347838 TI - Capillary electrophoresis: anticipating the state of the art at an early stage. PMID- 3347839 TI - Expression of the murine Duchenne muscular dystrophy gene in muscle and brain. AB - Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations. PMID- 3347841 TI - [Disorders of fracture healing in the conservative treatment of tibial fractures- a preventable complication?]. PMID- 3347840 TI - Human immunodeficiency virus may encode a novel protein on the genomic DNA plus strand. AB - The genome of the human immunodeficiency virus (HIV) is known to contain eight open reading frames (ORFs) on the minus strand of the double-stranded DNA replicative intermediate. Data presented here indicate that the DNA plus strand of HIV contains a previously unidentified ORF in a region complementary to the envelope gene sequence. This ORF could encode a protein of approximately 190 amino acid residues with a relative molecular mass of 20 kilodaltons if translation began from the first initiation codon. The predicted protein is highly hydrophobic and thus could be membrane associated. It is possible, therefore, that the HIV genome encodes a protein on antisense messenger RNA. PMID- 3347842 TI - [Biomechanical studies of the human elbow joint]. PMID- 3347843 TI - [Surgical treatment of clavicular fractures]. PMID- 3347844 TI - [Surgical management of dislocated fractures of the proximal segment of the radius]. PMID- 3347845 TI - [Old and neglected shoulder dislocations as indications for Bankart's operation. Report of experiences in the tropics and contribution to accident surgical practice in Third World countries]. PMID- 3347846 TI - [Arthroscopic operation in a general hospital. Results following 227 arthroscopic meniscectomies]. PMID- 3347847 TI - Living arrangements and women's health. AB - The recent changes in the traditional patterns of living arrangements in the U.S.A. raise interest in their consequences for the well being of the individuals involved. In this paper the physical health of women in different living arrangements was studied. It was suggested that living arrangements differ in the degree of adult support and the nurturant responsibilities that often accompany women's social support. Since previous research seems to indicate that social support promotes health and nurturant obligations constrains it, it was predicted that women whose living arrangements offer steady adult support with slight nurturant responsibilities will be healthier than women whose living arrangements offer both, and that women whose living arrangements involve nurturant responsibilities without adult support will be the least healthy. It was also suggested that the more legitimate and socially acceptable are one's living arrangements, the fewer the social costs incurred. Health was measured by three health status and three illness behaviour indices. Data were taken from the NHIS of 1979, and a multiple regression analyses were conducted. When a health profiles approach was taken, the health of women in different living arrangements ranked according to the hypotheses: women who live with their parents are the healthiest, followed by those in children/relatives' households; women head of families are the least healthy, just preceded by those living alone; women who live with their husbands or with unrelated persons are intermediate, and do not differ from each other. PMID- 3347849 TI - National Health Interview Surveys for health care policy. AB - Eleven National Health Interview Surveys (NHIS), from nine countries are reviewed to describe their objectives, topics and methods. The NHIS-data are evaluated in terms of their validity and reliability as well as their usefulness for health care policy decisions. With some modifications in design and methods, NHISs have potential for collecting recent and policy-relevant data. Suggestions are offered to improve the usefulness of NHIS-data for health care policy. PMID- 3347850 TI - Smoking and the female professions: pre-occupational influences on the behaviour of recruits to nursing and teaching. AB - A questionnaire and interview study of female recruits to nursing and teaching showed that occupational differences in the prevalence of smoking are already established at entry to training. The social characteristics of the smokers in the sample corresponded to those of women smokers generally. Differences in education and social origin contributed to occupational variations in behaviour. The influence of sibling behaviour and parental opinion operated differently within the two occupational groups. The psychological attributes of individuals attracted to a particular profession may also contribute to occupational patterns, specifically risk-taking and a concern for personal freedom. PMID- 3347848 TI - Intestinal helminthiases in relation to the socioeconomic environment of Panamanian children. AB - A cross-sectional investigation was made into ascariasis and nutritional status in Panamanian preschool children from October 1983 to July 1984. Within this framework, an analysis was undertaken of possible relationships between a range of intestinal helminthiases and the socioeconomic status of the participants. Attention was paid to caregiver's education, parental occupation, family earnings, quality of housing and sanitation in the assessment of socioeconomic status. On this basis, strong associations were established between the socioeconomic status of the children and infection with Ascaris lumbricoides, Trichuris trichiura and hookworm. In general, the prevalence of single and multiple helminth infections was significantly higher in children living in housing made of wood or bamboo than in those living in housing made of concrete blocks. The same pattern applied to levels of sanitation. Ascaris lumbricoides occurred more frequently in children of mothers with the least formal education and in children living in relatively crowded conditions. Evidence was also obtained to indicate that the intensity of the intestinal helminth infections was greater in the children from the poorer environment. Since children from poorer socioeconomic conditions might be more exposed to infective stages than those from a better environment, the possible role of socioeconomic factors in contributing to the predisposition of some individuals to harbour large worm burdens of intestinal helminths was briefly discussed. PMID- 3347851 TI - Coffee drinking among Finnish youth. AB - The suggestion that coffee may have negative health effects has made coffee drinking habits medically interesting. This paper reports upon coffee use among young people and describes how coffee-users differ from non-users. Data comes from questionnaires from representative nationwide samples of 12-18-year-old Finnish youth in 1977-1985. Their coffee use decreased from 1977 to 1985, and the decrease could be seen in all age and socio-demographic groups studied. In 1981, 35% of the girls and 45% of the 12-year-old boys drank coffee daily. For 18-year olds the corresponding percentages were 67 and 75, and the mean number of cups consumed per day was 2.3 and 3.1. Compared to the non-users, the coffee-users were from lower social classes, lived more often in the countryside, and had poorer school achievement. Health-damaging habits such as smoking were more common among the coffee-users, their perceived health was somewhat poorer, and they seemed to mature earlier. The difference in regard to health disappeared after adjusting for differences in socio-demographic background and health habits. The heavy users (four cups or more a day) usually differed more from the non-users than did the moderate users (one to three cups daily). PMID- 3347853 TI - Stress and coping in relation to health and disease. PMID- 3347852 TI - Immunization coverage of children in a semi-urban village panchayat in Nepal, 1985. AB - This research project, funded by the Yale International Committee and in cooperation with UNICEF, Nepal, used a questionnaire to survey and assess the immunization status of children 3 years or younger in a semi-urban panchayat. Mothers of children ranging in age from less than 1 month to 3 years were questioned both about immunization status of their children and their own use of health care and specific sources of information. 54% (124/228) of the children had received at least one vaccine and only 4% (10/228) had full coverage with the recommended vaccines (3 doses of DPT and TOPV, one dose of measles and BCG). The mean number of vaccinations for males was significantly greater than that for females (2.12 vs 1.39, P = 0.007, t = 2.80). Male children were twice as likely to have received vaccines as females (76/122, 62% vs 48/106, 45%; Odds Ratio = 2.00). Children born at a hospital were more likely than those born at home to have been vaccinated (23/34, 68% vs 101/194, 52%; P = 0.05, chi 2 = 12.52, d.f. = 2). Most mothers obtained health information from neighbors (38%), radio (22%), or health workers (18%), and 85% of the children were born at home; the majority (164/228, 72%) of the women received assistance during childbirth, 28% of the total reported self delivery. More than 70% of the women felt that vaccinations were good preventive measures. The study results suggest that health education about immunization efforts should be focused on women and these efforts should be intensified. PMID- 3347854 TI - Life events, combat stress reaction and post-traumatic stress disorder. AB - The implication of life events just preceding a war in acute combat stress reaction and chronic PTSD were assessed in a sample of 716 Israeli combatants. Results show that life events were unrelated to combat stress reaction but were related to subsequent PTSD. Conceptual and methodological issues were discussed to explain the results. PMID- 3347856 TI - Changing health behaviour outcomes in asthmatic patients: a pilot intervention study. AB - Starting from a prior study, in which cognitive and coping variables proved to be related to well-being, the use of medical resources and the absence from work in asthmatic patients, the authors constructed a cognitive-educational (a combination of health education and rational emotive behaviour modification) intervention programme aiming at altering coping behaviour in asthmatic patients in order to influence emotional distress and use of medical resources. The effects of the programme were assessed by means of a pre-test-post-test control group design. The programme was offered to ten patients and their partners. Both before and after the intervention cognitive attitudes (optimism, locus of control, and shame or stigma), coping behaviour in attack situations (minimizing the seriousness of the attack, rational action and reacting emotionally), coping in daily life (maintaining a restrictive life-style, focussing on asthma and hiding asthma), emotional distress (anxiety, anger, and depression), and the use of medication were measured in the experimental and control group. It was found that patients who received the programme became less preoccupied with their asthma and reported significantly less emotional distress (anxiety and anger) in daily life. In addition, they used less maintenance medication (corticosteroids). The authors wish to stress the importance of using medical variables such as the number of attacks as covariates in this type of research. PMID- 3347855 TI - Migraine and defense mechanisms: psychophysiological relationships in young females. AB - Two psychological defense mechanisms, repression and self aggression, were studied in 23 young female migraine patients who had not been receiving treatment for their complaints and in 23 relatively headache free matched controls. All subjects were psychology students. Each subject was classified as high or low on repression and self aggression using the defense mechanism inventory. During three separate sessions: adaptation, intelligence test and real-life stress (an examination which was part of the psychology curriculum) pulse amplitudes of the temporal and digital arteries, frontal, temporal and corrugator EMGs, forehead temperature, skin conductance, and heart and respiration rate were measured. The migraine patients showed a trend towards more repression of their emotions and significantly more self aggression than the controls. Self aggression appeared to be positively associated with the headache frequency in the migraine group. With regard to the physiological measurements, in both groups repressors showed a modest tendency to enhanced sympathetic activity. Self aggression was not found to be related to any physiological measure of sympathetic activity, but, instead, related to less temporal blood flow. In general, associations were found between psychological defense mechanisms and physiological activity, which is suggestive of the existence of physiological pathways along which emotional inhibition might contribute to an attack of migraine after a stressful situation. PMID- 3347857 TI - Social support and occupational stress: a causal analysis. AB - This study is aimed at gaining insight into the role of social support provided by coworkers and supervisors in the reduction of job-stress. It is emphasized that, despite the inclusion of social support as an important variable in theoretical models of job stress, research on this issue is plagued by a lack of conceptual clarity, disagreement on definitions, and divergent operationalizations. Furthermore, there is little strong empirical evidence for the role of social support in alleviating job stress. Moreover, because of the use of cross-sectional designs, causal interpretations are often impossible. In this study, an attempt was made to assess the causal direction of the relationships between social support, stressors and strains, by employing a longitudinal panel design and LISREL analysis. Subjects consisted of 2034 employees of 21 Dutch companies from the eastern part of the Netherlands. All filled out a questionnaire on organizational stress and social support, and underwent a medical examination. Parts of the sample participated in two follow up measurements. The results showed that individuals from the highest occupational levels as well as those from the lowest perceived less social support than other individuals. Furthermore, the respondents consistently reported that coworkers provide more support than supervisors. Only in the group with the lower occupational level did social support have a causal effect upon most stressors, indicating that social support indeed reduces role ambiguity, role overload, role conflict and job future uncertainty. However, there was not much evidence for a causal effect of social support by the coworkers upon the stressors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3347858 TI - Investigating the frequency of nursing stressors: a comparison across wards. AB - Intensive care unit stress has become an area of expanding enquiry. However the research evidence suggests that certain kinds of stressors are commonly encountered by all nurses irrespective of their nursing specialty. The frequency with which a range of stressors occurred in different wards was examined by using a nation-wide sample of 2500 New Zealand nurses. The results indicated that while intensive care-critical care wards were on average more likely to experience "difficulties involved in nursing the critically ill" than other wards, medical, continuing care and orthopaedic wards experienced in comparison more stressors more frequently. These results were discussed in terms of their implications for intervention and training. PMID- 3347859 TI - Penetrating facial trauma: a management plan. AB - Penetrating wounds of the face present a spectrum of injuries and multiple management dilemmas. The surgeon's first concern remains the establishment of a proper airway and control of life-threatening injuries. Selected ancillary diagnostic procedures should be used to confirm vascular, aerodigestive, or central nervous system injuries. Diagnosis of injuries may require arteriography, endoscopic examination, barium studies, computerized tomography, and detailed ophthalmologic examination. We review 16 cases of penetrating facial trauma treated at the University of South Alabama Trauma Center over a one-year period. The injuries resulted from 13 gunshot wounds and three stab wounds. Injuries of the central nervous system occurred in three patients, mandibular fractures in four, optic nerve or globe injury in three, and maxillary sinus fracture in seven. Our experience with these patients demonstrates the spectrum of injuries and serves as a basis for a management algorithm. PMID- 3347860 TI - Painful edema of the arm after insertion of single-needle subclavian vein dialysis catheters: pathogenesis and treatment. AB - The percutaneous subclavian vein hemodialysis catheter, which is widely used for vascular access in patients with renal failure, can give rise to several complications. Asymptomatic stenosis or occlusion of the subclavian vein due to these catheters can lead to painful arm edema if further dialysis accesses are constructed in the ipsilateral arm. This complication can lead to loss of valuable dialysis fistulas or grafts. We present six cases of this complication, along with management alternatives, which include conservative elevation, ligation of shunts, and surgical bypass of stenosed veins. Awareness of this complication should encourage early evaluation of patients who have had subclavian catheters and guide future placement of dialysis shunts. To preserve dialysis access sites, we advise an individualized approach to each patient who develops this painful arm edema. PMID- 3347861 TI - Changes in calcium and magnesium metabolism in essential arterial hypertension. AB - We studied 60 hypertensive patients (35 men and 25 women with an average age of 40 years) for signs of metabolic changes, with special emphasis on the relationship between the calcium and magnesium levels. The control group comprised 37 normotensive subjects (19 men and 18 women with an average age of 39 years). We studied the total serum calcium level (measured by atomic absorption), the ionized serum calcium level (by Nova 2 testing), and the plasma protein level, and we did coefficiency studies of the creatinine clearance and calcium and magnesium levels in 24-hour urine collections. In the hypertensive group, the ionized calcium level was significantly lower than that of the control subjects (P less than .001); the total serum calcium level was also lower, but the difference was of less statistical significance (P less than .05). There was no difference in serum magnesium levels between the two groups. There was a highly significant correlation between the total serum calcium level and the serum magnesium level (P less than .001) in the normal subjects; this correlation was not found in the hypertensive group. An increase in calcium and magnesium excretion was found in the 24-hour urine collections of the hypertensive group (P less than .001) (coefficient expressed as fractionated excretion of calcium and magnesium). There was also a high correlation between urinary excretion of calcium and magnesium (P less than .001) in the hypertensive subjects. Thus, the hypertensive subjects had changes in calcium metabolism that were related to magnesium levels. We suggest, therefore, that these two factors be studied simultaneously in evaluating patients with essential arterial hypertension. PMID- 3347862 TI - Pocket computer for interpretation of office spirometry. AB - Office spirometry is an integral part of the evaluation of any patient with known or suspected lung disease. Though accurate and affordable bellows-type spirometers are available to clinicians, the available microprocessors that calculate test results markedly increase the cost of the equipment. I have successfully used an inexpensive pocket computer programmed to provide predicted values and interpretation of test results, printing this information in a format suitable for mounting in the office chart. The reliability of the results and interpretations permits convenient and low-cost pulmonary function testing in office patients when clinically warranted. PMID- 3347863 TI - Orthopedic pitfalls in emergency medicine. AB - Acute orthopedic problems make up a large part of everyday emergency department practice. Misdiagnosis of these injuries often results from failure to consider certain clinical entities as a cause of the patient's complaints, and may result in unnecessary complications for the patient. Indeed, missed orthopedic injuries are the leading cause of malpractice claims in emergency medicine. The orthopedic injuries that most notoriously escape detection by the primary care physician are closed tendon injuries of the hand, carpal bone injuries, occult fractures about the elbow, femoral neck fractures, posterior dislocation of the shoulder, epiphyseal plate injuries, fractures of the pubic ramus, patellar tendon rupture, Lisfranc injuries, compartment syndromes, and multiple injuries. If the physician is unaware of these entities when evaluating the patient, he will not make the diagnosis. This review is designed to heighten the primary care physician's awareness of these injuries, which are a common source of problems in the emergency department. PMID- 3347864 TI - Hyperthermia, rhabdomyolysis, and myoglobinuric renal failure after recreational use of cocaine. AB - A patient had hyperthermia, rhabdomyolysis, and myoglobinuric renal failure after the recreational use of cocaine. We attribute this to the pyrogenic properties of cocaine and environmental factors. The use of cocaine during summer months or in areas with high ambient temperatures should alert physicians to the development of hyperthermia with or without seizures. Prompt recognition of the ensuing complications including mixed metabolic acidosis, rhabdomyolysis, and renal failure can result in appropriate and effective treatment. PMID- 3347865 TI - Suprasellar mass lesion with unusual magnetic resonance imaging characteristics. AB - Our case emphasizes the complex nature of signal abnormalities observed with MRI and underscores that a given histopathologic lesion (such as craniopharyngioma) may have variable appearances upon imaging with this modality. PMID- 3347866 TI - Congenital toxoplasmosis in an infant with hydrops fetalis. AB - We have described an infant born with severe hydrops fetalis due to congenital toxoplasmosis. Although uncommon, toxoplasmosis should be considered in the differential diagnosis of hydrops fetalis, particularly when the preliminary clinical work-up suggests a nonimmunologic basis for the hydrops. Although the clinical outcome in an infant as severely affected as this one will remain poor, the therapy for toxoplasmosis has improved over the years, and with quick diagnosis of the disease, a less severely affected infant may have a better prognosis. PMID- 3347867 TI - Transdermal scopolamine as a cause of transient psychosis in two elderly patients. AB - We have described two elderly patients who had psychosis after beginning transdermal scopolamine therapy. In both cases, changes in mental status resolved promptly when the medication was discontinued. PMID- 3347868 TI - Primary melanoma of the common bile duct. AB - We have described what we believe is the first reported case of primary melanoma of the common bile duct. The presenting sign was obstructive jaundice. An extensive evaluation for another primary source was unrevealing. Despite a Whipple procedure, the patient's condition deteriorated rapidly. PMID- 3347869 TI - Rhinocerebral mucormycosis in an anephric patient. AB - We have described a fatal case of rhinocerebral mucormycosis in a stable anephric patient who was not diabetic and was not receiving immunosuppressive therapy. In a literature search from 1966 to the present, ours is only the second case of a stable dialysis patient reported with this illness, and it is the only reported fatality. PMID- 3347870 TI - Short-term treatment of streptococcal endocarditis. PMID- 3347871 TI - Early diagnosis of overwhelming Vibrio vulnificus infections. PMID- 3347872 TI - ALS. PMID- 3347873 TI - Typhoid fever with unusual clinical features. PMID- 3347874 TI - Twiddler's syndrome: another twist. PMID- 3347875 TI - Hematocrit level as a predictor of death in the elderly. PMID- 3347876 TI - Selection of medical students. PMID- 3347877 TI - Trauma--an increasing problem. PMID- 3347879 TI - Progressive familial heart block (type I). A follow-up study after 10 years. AB - A follow-up study was done on 55 patients, all members of families with type I progressive familial heart block (PFHB) examined during 1977. Of the 55 patients 5 had died, 17 had normal ECGs while 7 with previously abnormal ECGs remained unchanged. All the others had progressed to a more severe form of heart block and 8 of them had received permanent pacemakers. These findings again emphasize the importance of regular ECG follow-up examinations of members of PFHB families. PMID- 3347878 TI - Phenotypic expression of the HLA-linked iron-loading gene in the Afrikaner population of the western Cape. AB - A previous study conducted on a group of Afrikaans-speaking subjects in the south western Cape indicated a high frequency (0.115) of the HLA-linked iron-loading gene which causes idiopathic haemochromatosis. The results of phenotypic and genotypic studies on the first degree relatives of identified homozygotes and heterozygotes are now reported. There was considerable heterogeneity of phenotypic expression in the group of heterozygotes, with overlap between the homozygous and heterozygous subjects. The heterozygous relatives of heterozygous index cases, who had been identified on the basis of a serum ferritin concentration greater than 400 micrograms/l, appeared to have more frequent and more marked abnormalities of iron measurements than the heterozygote relatives of homozygous index cases (serum ferritin value greater than 400 micrograms/l, percentage transferrin saturation greater than 60). This suggests that the screening test was identifying a group of more significantly affected heterozygotes, with biochemical abnormalities that overlapped with the identified homozygotes. The index cases were followed up over a period of 5 years and during this time the 7 subjects diagnosed as heterozygotes showed a progressive increase in serum ferritin concentrations, which suggests some iron accumulation. Individual pedigrees included instances of gene recombination within the major histocompatibility complex, and of probable false-positive genotype assignment. The overall results confirm a high frequency of the gene in this particular community. PMID- 3347880 TI - Treatment of ventricular septal defect after myocardial infarction. AB - Between 1978 and 1984 6 cases of ventricular septal defect after myocardial infarction were referred to this hospital. All 6 patients underwent cardiac catheterisation, had severe pulmonary hypertension and large left-to-right shunts (mean 64%). They were treated with high doses of diuretics and vasodilators, and underwent delayed surgery 6 weeks after rupture. Follow-up is from 1 to 7 years. There has been 1 late, non-cardiac death. The remainder are well. In our experience patients with congestive cardiac failure complicating ventricular septal defect after infarction can be stabilized initially on diuretic and vasodilator therapy, and surgery can safely be deferred until septal fibrosis allows adequate closure. PMID- 3347881 TI - Parkinson's disease in blacks. Observations on epidemiology in Natal. AB - Black patients with idiopathic Parkinson's disease (PD) present for neurological consultation much less frequently than white or Indian patients. That this is due to true rarity of PD among blacks is suggested by the observation that blacks with motor neuron disease and secondary parkinsonism are treated in numbers comparable with whites and Indians. These conclusions are derived from a series of 2,638 inpatient neurological consultations and from data on levodopa usage in three major hospitals in Durban. Lower life expectancy and failure of old people to attend hospital may be factors in the apparent low prevalence of PD among blacks, but other undetermined factors must play a part. PMID- 3347882 TI - Drug therapy for Graves' disease in blacks--very low rates of remission. AB - The rates of remission after a course of antithyroid drugs in 71 black and 45 white patients with Graves' disease were compared. One year after stopping therapy 27% of blacks and 47% of whites were in remission (P less than 0.01); at 2 years the proportions were 7% and 27% respectively (P less than 0.05). Small size of goitre only was a weak predictor of remission; duration of therapy did not influence the outcome. HLA A2 and B17 may be less frequent in black patients who remain in remission (P = 0.048 and 0.067 respectively). The data suggest that it is not worth while undertaking a trial of medical therapy in unselected black patients with Graves' disease. PMID- 3347883 TI - Childhood deafness in Zimbabwe. AB - An investigation involving 885 children in five institutions for the deaf in Zimbabwe was conducted with a view to determining the cause of hearing loss. The cause of deafness in 40% of cases was an infectious or infective disorder, while in 43% the basic defect was unknown. There was a seemingly high prevalence of autosomal recessively inherited undifferentiated deafness among children from the Shona tribe. Conversely, an apparent underrepresentation of genetic syndromic disorders was evident in both major tribal groups. Possible explanations for these findings are discussed. PMID- 3347884 TI - Profile analysis of pupils at a school for black deaf children. A pilot study. AB - The pupils at a school for black hearing-disabled children were clinically investigated and the findings were analysed with regard to age, sex, and nature and possible cause of deafness. A total of 169 children were examined. The majority were boys, and 95% were hearing-disabled before the age of 3 years. One tenth of the children had a positive family history. An apparent cause could be established with a degree of certainty in only 30% of cases. PMID- 3347885 TI - Selection of medical students--effect on class composition of using non-academic criteria. AB - The attributes of 2,304 applicants for admission to the University of the Witwatersrand Medical School were analysed. Those measured by previous academic performance, biographical history and assessment at interview were significantly different. Inclusion of non-academic criteria in admission decisions broadens the personal attributes of the class, and alters the ethnic and gender composition, without affecting subsequent failure rate. PMID- 3347886 TI - Selection of medical students at a medical faculty in South Africa. AB - The selection procedure at one medical faculty in the RSA was investigated. Students were admitted to the M.B. Ch.B. course on the basis of school results. Four groups were studied: matriculants; those selected after completing the 1st year of a B.Sc. course; those who had completed a full B.Sc. course; and those who had experience and other qualifications after leaving school. The matriculants were by far the largest group and the analysis of their marks received emphasis. Students who registered for their 1st year in 1980-1983 were followed up until the middle of their 3rd year. In total 635 students were assessed. The students' school results were compared with their preclinical marks. Chi-square tests for independence, multiple regression analysis, Pearson correlation coefficients and canonical correlation analysis were carried out. Although the results reflected a significant relationship between good selection marks and preclinical achievement, the strength of the association was too small for selection marks to have any reliable predictive value for an individual student. There was a low drop-out rate (5.4%) during the 1st year of study, but this rate increased threefold to 17.2% during the remaining preclinical period. This may indicate that the selection criteria were not specific enough to avoid this relatively large loss of students. PMID- 3347887 TI - [Oxygen balance in the normal dog myocardium with increased concentrations of inhaled anesthetics]. AB - Myocardial oxygen supply and demand in the normal dog were evaluated as the concentration of halothane, enflurane or isoflurane was increased. Although coronary blood flow decreased as the anaesthetic gas concentration increased, the O2 supply-to-demand ratio remained stable owing to a decrease in the myocardial O2 consumption. PMID- 3347888 TI - Lesser-curve ischaemic necrosis mimicking a gastric ulcer--a complication of highly selective vagotomy. A case report. AB - Ischaemic necrosis of the lesser curve of the stomach is thought to be a specific but rare complication of highly selective vagotomy. While it commonly presents as a free perforation, it may also present as sloughing of the mucosa only, a gastric fistula or a sealed perforation of the lesser curve mimicking a chronic gastric ulcer. We describe a case in which ischaemic necrosis of the lesser curve presented as a chronic gastric ulcer from a sealed perforation. PMID- 3347889 TI - Privatisation and medicine. PMID- 3347890 TI - Occupational health legislation. PMID- 3347891 TI - Abdominal aortic aneurysm--a possible cause for reduced afterload. PMID- 3347892 TI - Detection of changes in arterial haemoglobin saturation with the pulse oximeter. PMID- 3347893 TI - Mushroom (Amanita phalloides) poisoning in the Ciskei. PMID- 3347894 TI - The acute abdomen. PMID- 3347895 TI - The Ophthalmic Knowledge Assessment Program (OKAP): a personal view. AB - This essay relates the historic process that led to the development of the Ophthalmic Knowledge Assessment Program (OKAP) as an established component of ophthalmic training in the U.S.A. Begun in the early 1960s as an evaluative examination for residents at the University of Florida, the first national OKAP examination took place in May 1968, with over 85% of all eye training programs participating. It was later incorporated into the Continuing Education program of the American Academy of Ophthalmology and Otolaryngology, where it prospered. Beginning January 1980 the OKAP was combined with American Board of Ophthalmology exam, thus establishing a single, unified national exam. PMID- 3347896 TI - [We will constantly be confronted with the fact that we drink coffee]. PMID- 3347897 TI - [Executive Board. Delegates' education should also be adapted]. PMID- 3347898 TI - [Executive Board. Why do nurses secure work in psychiatry?]. PMID- 3347899 TI - [Profound disagreement about new mental disease legislation]. PMID- 3347900 TI - [A good job gives value to life--a poor job...]. PMID- 3347902 TI - [Health activities among Afghan refugees]. PMID- 3347901 TI - [Diet and exercise--health education project of the 19th class]. PMID- 3347903 TI - Zinc amelioration of cadmium toxicity on preimplantation mouse zygotes in vitro. AB - Zinc, at a concentration of 5 or 10 micrograms/ml medium, has been shown to protect mouse preembryos in vitro from the toxicity of cadmium at a concentration of 5 micrograms/ml medium after a simultaneous treatment of the ions from four cell to morula or from morula to blastocyst for 24 hours. Such an amelioration indicates that cadmium toxicity is a result of the unique property of the cadmium ion and is not due to an alteration in the culture medium after the addition of an extra metallic ion. Zinc probably ameliorates cadmium-treated mouse preembryo by competing with cadmium for uptake or some other metabolic processes. In view of the well-documented competition between cadmium and zinc ions for binding sites in many other cell types, some macromolecules to which similar divalent metallic ions bind competitively may also exist in the mouse preembryo. This suggests that a protective mechanism dependent on the metal-metal interactions begins to operate in the mouse preembryo at a very early stage of differentiation before implantation. PMID- 3347904 TI - Evaluation of a temporal increase in ventricular septal defects: estimated prevalence and severity in northeastern New York, 1970-1983. AB - A marked increase or "epidemic" in ventricular septal defects (VSD) in recent years has been reported by the Center for Disease Control. Many pediatric cardiologists believe that this increase is simply a reflection of more intensive diagnosis and evaluation of infants throughout the country. Yet to our knowledge there has been no objective evidence for this explanation. We evaluated this possibility by considering records on live births occurring in 1970-1983 in the counties surrounding Albany, New York. In that period a single group of pediatric cardiologists has been evaluating all infants with suspected or confirmed cardiac defects in this area. We limited this analysis to ventricular septal defects unassociated with any cardiac syndrome complex. Thus, VSDs occurring as part of cyanotic heart disease or other complex cardiac "syndromes" were excluded. Consistent with the reported national trend, the estimated prevalence rate of ventricular septal defects diagnosed under 1 year of age in this period has increased from 1.0 per 1,000 live births in 1970 to 4.0 per 1,000 in 1983.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3347905 TI - Light microscopic studies on the pathogenesis of exencephaly and cranioschisis induced in the rat after neural tube closure. AB - Administration of a single dose of cyclophosphamide (20 mg/kg) to Charles Foster (CF) rats on day 12 of gestation (i.e., well after neural tube closure) results in exencephaly in almost 100% of living fetuses at term (Padmanabhan, '84). Following the same treatment, embryos/fetuses were collected at various intervals of time (from 8 hr to day 19 of gestation) and studied histologically. At 10 hr after treatment, the neuroepithelium (NE) of the brain vesicles and the neural crest-derived ganglia exhibited pronounced cell death. By day 13, cell death appeared to be more intense and extensive in the NE; the mesenchyme (ME) was less proliferative and was loosely organized. In the following days, the NE presented vacuolizations which coalesced into cavities; these cavities were often bilaterally symmetrical, contained free neuroblasts and erythrocytes, and subsequently opened into the ventricles. The choroid plexus hypertrophied, the ventricles distended, and the NE gradually became very thin. The hypertrophied capillaries of the ME cleaved through the NE, thus delaminating an outer stratum. Subcutaneous blebs developed over the brain vesicles and communicated with the cavities in the brain. Thus the ventricles and the blebs came into direct communication. The ME dorsal and lateral to the brain was loose, and at no site was it organized into the skull primordium. By day 19, there were clear and multiple discontinuities in the walls of the brain. Initial cell death and vacuolization in the NE, inhibition of ME proliferation followed by hypertrophy of the choroid plexus, and possibly enhanced intraventricular pressure and hemorrhage and edema of the ME seem to underlie this process of reopening of the closed neural tube.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3347906 TI - Hyperthermia-induced exencephaly in mice: effect of multiple exposures. AB - Pregnant LM/Bc female mice were given a 10-minute hyperthermic exposure in a 43 degrees C waterbath during the period of neural tube closure. On day 15.5 of gestation, the females were killed, and the fetuses were examined for exencephaly. Following a single treatment on day 8.0, 8.5, 8.75, or 9.0 of gestation 1.7, 13.6, 2.9, and 0.8% of the respective fetuses displayed exencephaly. With two treatments, one on each of gestational days 8.5 and 8.75, or three treatments, one on each of gestational days 8.5, 8.75, and 9.0, the percentage of exencephalic fetuses increased to 28.3 and 59.3%, respectively. The increased response to multiple treatments was not due to an increase in the number of susceptible embryos but rather was due to the increased number of treatments. The results of this study suggest that with increasing numbers of treatments, the embryo's ability to recover from the hyperthermic exposure is lessened, resulting in an increase in exencephaly. PMID- 3347908 TI - Development of rat embryos cultured in serum prepared from rats with streptozotocin-induced diabetes. AB - The effects of 40, 50, and 60 mg/kg streptozotocin (SZ) on the body weights and the glucose concentration and the osmolarity of the serum of adult rats were determined. Serum prepared from these SZ-dosed rats was used in embryo culture experiments to investigate effects of diabetic serum on rat embryos during organogenesis. The diabetic serum resulting from each of the tested doses of SZ was teratogenic to 9.5-day rat explants (embryos and their membranes), causing a range of dysmorphic lesions including craniofacial defects, heart defects, and abnormalities of the branchial arches and the otic capsules. Explants cultured in serum prepared from rats dosed with 60 mg/kg SZ also showed abnormal morphology of both the visceral yolk sac and the embryonic blood cells in the yolk sac capillaries. The development of explants repeatedly transferred between control and diabetic serum indicated that the severity of the dysmorphic effect was dependent on the duration of exposure to diabetic serum. The alternation of sera did not in itself appear to be damaging to the embryos. Explants cultured in control serum, control serum with its glucose concentration increased to that of the diabetic serum, or diabetic serum all took up the same amount of glucose from their culture medium; 30% of the embryos from the diabetic serum were abnormal compared to only 4% from the control serum and the control serum plus glucose. PMID- 3347907 TI - Strain differences in teratogenic susceptibility to trypan blue between WM and BDIX rat strains. AB - Female rats of WM (Wistar-Mishima)/Nem strain were mated with WM/Nem (group W) or BDIX/Nem males (group WB), and BDIX/Nem females were mated with BDIX/Nem (group B) or WM/Nem males (group BW). On day 8 of gestation, pregnant females were treated intraperitoneally with 1% aqueous solution of trypan blue at a dose of between 20 and 120 mg/kg of body weight. On day 20 of gestation, fetuses were examined for external, visceral, and skeletal malformations. In group W, fetal mortality increased dose dependently at doses higher than 20 mg/kg, and incidences of external, visceral, and skeletal malformations were significantly higher than control at doses of 30 mg/kg and more. In group B, fetal mortality and the incidence of external malformations were significantly higher than control only in the group treated with 120 mg/kg, and no significant increase of visceral and skeletal malformations was shown. It was confirmed that BDIX strain is much more resistant to trypan blue teratogenicity than WM strain. In group BW, nearly the same teratogenic effects were shown as in group W in terms of fetal mortality and incidence of malformations. However, in group WB, teratogenic effects were not so remarkable as in group BW, suggesting patroclinous effects in teratogenic susceptibility to trypan blue. In group BW, sex differences in teratogenic susceptibility were found; male fetuses were more susceptible to trypan blue than females. PMID- 3347909 TI - Interlitter variability in fetal body weight in mouse offspring from continuous, overnight, and short-period matings. AB - When female mice of the Jcl:ICR strain were mated with a male either (1) continuously throughout the day or (2) overnight or (3) during 2 hours in the morning at light period, the interlitter variability of fetal body weight on the 18th day of gestation was smallest in the group with short-period mating. Thus, in the embryonic stage-specific teratological experiments, this mating schedule is advised. Even for routine reproductive toxicity testing protocols, the short period mating may be preferable for the purpose of increasing test sensitivity. PMID- 3347910 TI - The effects of in vivo administration of teratogenic doses of vitamin A during the preimplantation period in the mouse. AB - To examine the effects of vitamin A administered during the preimplantation period, pregnant C3H mice were exposed to teratogenic doses of the vitamin 60 h after copulation. Fetuses were examined for gross abnormalities on the 18th day of gestation and viability, cell number, mitotic index, and chromosome structure were assessed in 81-h blastocysts to determine whether embryotoxic effects were apparent in the preimplantation embryo. There was a reduction in the fetal weight of 18-day fetuses treated in this manner with 15,000 and 30,000 IU vitamin A (p less than 0.0003 in each case), and doses of 10,000 IU and greater were associated with a significantly higher incidence of gross abnormalities. Malformations included exophthalmos, anophthalmia, microphthalmia, exencephaly, exomphalos, and limb defects. Administration of 30,000 IU vitamin A resulted in resorption and intrauterine death in 70% of cases. There was no indication that vitamin A adversely affected 81-h blastocyst viability, cell number, mitotic index, and chromosome structure. The findings suggest that the teratogenic effects that were noted later in fetal life were the result of an action on the developing fetus of the vitamin at a stage later than 81-h and are consistent with the relative resistance of the preimplantation embryo to toxic injury. Persistence of vitamin A, either in the mother or the embryo, is the most likely explanation for the later expression of toxic injury, which is characteristic of the effects that are noted as a result of exposure to the teratogen during the period of organogenesis. PMID- 3347911 TI - Severe skeletal dysplasias following intrauterine exposure to ethanol. PMID- 3347912 TI - Association of intracranial hemorrhages with organic acidemias. PMID- 3347913 TI - Obstructive sleep apnea syndrome and depression. PMID- 3347915 TI - Proposal for determining supportive care only status. PMID- 3347914 TI - Acute renal failure secondary to intravenous pyelography in a child. PMID- 3347916 TI - The Texas Natural Death Act: the new law in a new light. PMID- 3347917 TI - Physician's nemesis: retention and release of medical records. PMID- 3347918 TI - [Analysis, clinical systematic aspects and differential diagnosis of involuntary movements]. PMID- 3347919 TI - [Tremor: clinical aspects and therapy]. PMID- 3347920 TI - [Involuntary movements in multiple sclerosis]. PMID- 3347921 TI - [Drug-induced involuntary movements]. PMID- 3347922 TI - [Extrapyramidal involuntary movement in childhood]. PMID- 3347923 TI - [Anatomic and pathophysiologic principles of involuntary movements]. PMID- 3347924 TI - Relationship between serum lipoproteins and hemostatic parameters in men with prostatic cancer. AB - Serum lipoprotein concentrations were related to hemostatic parameters in a group of 31 men before and during three different hormone treatment regimens for prostate cancer in an attempt to analyse to what extent the changes in these two systems correlate. In a correlation matrix the number of significant relationships at the 5% and 1% level corresponded to what could be expected by chance. The study thus failed to demonstrate any consistent relationship between any lipoprotein lipid concentration and the hemostatic parameters in men treated for prostate cancer. Most significant relationships were found for HDL-TG versus plasminogen, but the clinical significance of this observation is not clear. PMID- 3347925 TI - The effect of factor XIII and fibronectin on the viscoelasticity of fibrinogen surface layers. PMID- 3347926 TI - Effect of thrombin inhibitors on thrombin-induced platelet release and aggregation. AB - Thrombin-induced platelet activation was interrupted with hirudin or Dansylarginine N-(3-ethyl-1-5-pentanediyl) amide (DAPA) to study the time requirement for receptor occupancy by thrombin in promoting platelet responses at low (0.25 U/ml), intermediate (0.5 U/ml) and high (1 U/ml) thrombin concentrations. Each of these thrombin inhibitors suppressed adenosine triphosphate (ATP) release and aggregation by thrombin when added either before or simultaneously with thrombin or within seconds of the initiation of these responses by thrombin. If the inhibitors were added later, yet before aggregation or release was complete, no effect was present. The period of time for which active thrombin was required in order to promote these reactions had the following characteristics: (i) it is thrombin concentration dependent for a given response; (ii) it is longer for aggregation than for ATP secretion at each thrombin concentration; (iii) it is increased in platelets modified by chymotrypsin or platelets partially inhibited by antimycin A and 2-deoxy-D glucose, which have prolonged aggregation and ATP release responses. In direct comparison studies, the inhibitory effects of hirudin and DAPA were identical on aggregation and ATP release. Thrombin binding, under similar experimental conditions identical to those used to measure platelet activation, was prevented by hirudin, but not by DAPA. Therefore, the effect of DAPA on thrombin must be at the proteolytic site region and not at the hirudin-inhibitable platelet binding region. It is concluded from these studies that the tight coupling requirements for thrombin to induce platelet dense granule release and aggregation are directly dependent upon both the thrombin concentration and the rate of the individual platelet responses. Catalytic site integrity is required for the duration of this period of receptor occupancy. PMID- 3347927 TI - Peptides and monoclonal antibodies which bind to platelet glycoproteins IIb and/or IIIa inhibit clot retraction. AB - The rate of clot retraction in platelet-rich plasma was decreased by synthetic peptide analogues of fibrinogen and monoclonal antibodies each of which bind to the platelet plasma membrane glycoproteins IIb and/or IIIa. These and related data demonstrate that intact complexes of the glycoproteins IIb and IIIa are required for platelet-mediated clot retraction. PMID- 3347928 TI - Response of the cubital vein to occlusion and calcification of the abdominal aorta in patients with chronic renal failure on maintenance hemodialysis. AB - Dysfunction of vascular endothelial cells and accelerated calcification of the abdominal aorta were found in patients on maintenance hemodialysis. Indicators of vascular wall function, expressed as the amount of plasminogen activator and von Willebrand factor released during venous occlusion, suggested that the cubital venous wall in patients has normo- or hyper-responsiveness to occlusion. Calcification of the abdominal aorta on CT scan image was observed in most of patients including those of the ages of twenties years. The mean aortic calcification index (ACI), as an indicator of organic changes in vascular wall, was significantly higher in dialysis patients than in the nondialysis subjects. However, the mean values of indicators for vascular wall function decreased and ACI increased, as the period of treatment with hemodialysis became longer. A significant negative correlation was found between the mean ACI and most indicators of vascular wall function. The function of cubital vein was suggested to decrease in association with the progress in mural calcification of the abdominal aorta. We conclude that the alteration of the coagulation-fibrinolysis system induced by repeated hemodialysis may result from and continue to exacerbate endothelial damage, the consequence of which may be atherosclerosis. PMID- 3347929 TI - Inhibition by the antilipogenic antibiotic cerulenin of thrombin-induced activation of human platelets. AB - Upon incubation with an antibiotic cerulenin, human platelets lost their abilities to aggregate and to release serotonin or ATP in response to various stimuli such as thrombin, ADP, collagen and platelet activating factor. The loss of activities was dependent on both incubation time and cerulenin concentrations. As judged by 14C-serotonin release, concentrations of cerulenin required for the half-maximal inhibition of thrombin-induced activation were 5-10 and 70 micrograms/ml in the incubation for 120 min at 37 degrees C for washed platelets and those in platelet rich plasma, respectively. The cerulenin treatment also resulted in a significant inhibition of 14C-acetate incorporation into the lipid fraction of platelets, suggesting that de novo synthesis of fatty acids was inhibited by the treatment. No release of lactate dehydrogenase activity nor morphological changes in platelet structure was detected upon cerulenin treatment. When effects of cerulenin on intracellular Ca2+ concentration were examined, mobilization of intracellular Ca2+ by thrombin was significantly depressed in the cerulenin-treated platelets as judged by Fura2, Quin2 or chlortetracycline fluorescence. Since the influx of external Ca2+ is not essential to the thrombin-induced platelet activation (Rink, T. J. et al. FEBS Lett. 148 21-26, 1982), the results suggest that cerulenin-treatments affect the platelet function through the inhibition of intracellular Ca2+ mobilization. PMID- 3347930 TI - [The diagnostic value of the 'skyline' view for the radiographic study of the navicular bone in horses]. AB - The radiographic diagnostic value of Rose's palmaroproximal-dorsodistal ('skyline') projection and Oxspring's dorsopalmar projection of the equine navicular bone were compared, by examining radiographs of 102 navicular bones originating from 66 randomly selected horses with clinical evidence of lameness located in the navicular area. In 27 navicular bones essential information was obtained from the skyline view, 15 independently of Oxspring's projection and 12 in addition to this view. For 11 navicular studies the D.P. projection was the most important diagnostic view. In the other 64 navicular bones information obtained from both views was of equal diagnostic value. Based on these results it is suggested that the skyline projection be utilised as an additional view, especially if there is a significant discrepancy between the clinical and radiographic findings based on lateromedial and Oxspring projections, and if ill defined lesions of unknown significance are visible on the Oxspring projection. PMID- 3347931 TI - [The first 100 days of President Kampelmacher: 'My greatest worry is that I miss 20 percent of all veterinarians'. Interview by L.J.E. Rutgers]. PMID- 3347932 TI - Enzyme-linked immunosorbant assay (ELISA) of size-selected crotalid venom antigens by Wyeth's polyvalent antivenom. AB - The binding of Antivenom (Crotalidae) Polyvalent to fractions from crude venoms of eight crotalid and one viperid snake, obtained by high performance size exclusion chromatography, was determined with an indirect enzyme-linked immunosorbent assay (ELISA). Most of the large (greater than 30,000 mol. wt) molecular mass crotalid venom fractions were associated with high (greater than 0.7 absorbance units) ELISA values. Similarly, the medium (13,000-30,000 mol. wt) and small (less than 14,000 mol. wt) molecular mass crotalid venom fractions were coincident with moderate (0.3-0.7 absorbance units) and low (less than 0.3 absorbance units) ELISA levels. Some variability in this pattern was seen with individual venom fractions. A distinctly different pattern of ELISA values were observed with two rattlesnake venoms: the South American (Crotalus durissus terrificus) and Mojave desert (Crotalus scutulatus scutulatus) rattlesnakes. The elution profile from these venoms showed a progression of low to moderate ELISA values within the large molecular mass fractions. This pattern was followed by a decline to low ELISA values throughout the remainder of the elution profile. When saw scaled viper (Echis carinatus leucogaster) venom fractions were tested, only background ELISA values were detected with antivenom. Similarly, background ELISA values were associated with the small molecular mass fractions of all venoms tested. In addition, the elution position for the basic peptides of southern Pacific (Crotalus viridis helleri) and timber (Crotalus h. horridus) rattlesnake venoms showed minimal ELISA values. These data support the view that except for the venom of C. durissus terrificus and C. s. scutulatus, most antivenom antibodies bind large (greater than 30,000 mol. wt) venom fractions. Thus, antivenom contains minimal levels of antibodies to the basic peptides in these venoms. PMID- 3347933 TI - T-2 mycotoxin inhibits mitochondrial protein synthesis. AB - We investigated the effect of T-2 toxin on rat liver mitochondrial protein synthesis. Isolated rat liver mitochondria were supplemented with an S-100 supernatant from rat liver and an external ATP-generating system. We used an in vitro assay employing cycloheximide, an inhibitor of cytoplasmic protein synthesis, and chloramphenicol, an inhibitor of mitochondrial protein synthesis, to distinguish mitochondrial protein synthesis from the cytoplasmic process. Amino acid incorporation into mitochondria was dependent on the concentration of mitochondria and was inhibited by chloramphenicol. The rate of uptake of [3H]leucine into mitochondrial protein was unaffected by the addition of T-2 toxin and was not a rate-limiting step in incorporation. However, 0.02 micrograms/ml of T-2 toxin decreased the rate of protein synthesis by isolated mitochondria by 50%. The degree of protein synthesis inhibition correlated with the amount of T-2 toxin taken up by the mitochondria. While T-2 toxin is known to inhibit eukaryotic protein synthesis, this is the first time T-2 was shown to inhibit mitochondrial protein synthesis. PMID- 3347934 TI - Release of sarcoplasmic enzymes from skeletal muscle by Bothrops jararacussu venom: antagonism by heparin and by the serum of South American marsupials. AB - The venom of B. jararacussu induced a time- and dose-dependent (2-100 micrograms/ml) increase in the rate of release of sarcoplasmic enzymes (CK and LDH) from isolated rat and frog muscles. This effect, which we attribute to sarcolemmal damage by the venom, persisted in a Ca2+-free media, suggesting that phospholipase A activity was not required. The venom-induced enzyme release from the isolated muscles was reversibly inhibited by the sera (1-10 microliters/ml) of the marsupials Didelphis marsupialis aurita and Philander opossum, by an acidic glycoprotein fraction isolated from the opossum serum (50 micrograms/ml), and by heparin (50 micrograms/ml). Incubation of the B. jararacussu venom with opossum sera or heparin prevented the increase in plasma CK level observed in mice in which the snake venom (2.5-5.0 micrograms/g) was injected i.m. It is suggested that formation of acid-base complexes between basic myotoxins of B. jararacussu venom and either acidic components in the marsupial sera or the polyanionic heparin could account for the inhibition of the in vitro and in vivo effects of the venom on the release of sarcoplasmic enzymes from skeletal muscles. PMID- 3347935 TI - Brevetoxin binding: molecular pharmacology versus immunoassay. AB - Brevetoxin PbTx-3 isolated from Florida's red tide dinoflagellate Ptychodiscus brevis has been produced recently in tritiated form by reductive tritiation of brevetoxin PbTx-2. Tritiated PbTx-3 has been used as a specific probe in competitive radioimmunoassays developed to detect brevetoxins in food sources, and this probe has also been utilized to characterize the brevetoxin binding component in rat brain synaptosomes. Brevetoxins PbTx-2 and PbTx-3, possessing the same structural backbone (type-1) as the tritiated probe, and PbTx-1 and PbTx 7, possessing a second structural backbone (type-2), have been compared quantitatively in their individual abilities to competitively displace tritiated PbTx-3 from its specific binding site in each assay. Type-1 toxins displaced labeled probe with ED50 values of 20-22 nM and 12-17 nM in radioimmunoassay and synaptosomes, respectively. Type-2 toxins displaced labeled probe with ED50 values of 92-93 nM and 3.5-4.1 nM in RIA and synaptosomes, respectively. Synaptosome assays reflect potency of each toxin examined, while radioimmunoassay reflects structural similarities to the immunizing toxin PbTx-3. PMID- 3347936 TI - Pharmacokinetics of cyclosporine G in patients with renal failure. AB - The pharmacokinetics of the cyclosporine A (CsA, Sandimmune) analogue Nva2 cyclosporine, or cyclosporine G (CsG) was investigated in 6 patients with terminal renal failure after a 4-hr intravenous infusion (3.5 mg/kg) and after oral administration (600 mg) of the drug. Blood samples were collected up to 38 hr and CsG concentrations were measured by radioimmunoassay and high-performance liquid chromatography. The resulting pharmacokinetic parameters of CsG were similar to those described for CsA in the same patient population. Based on HPLC determinations, a mean terminal elimination half-life of 18.9 hr was calculated. The total body clearance was 0.55 L/hr/kg, the volume of the central compartment was 0.32 L/kg, and the steady-state volume of distribution was 5.97 L/kg. After oral administration maximum CsG concentrations in blood were reached between 2.5 and 3 hr, and the bioavailability was in the range of 24-55% (mean 36%). The ratios between the polyvalent RIA and HPLC determinations were considerably larger after oral dosing than after i.v. infusion. The blood-to-plasma ratio was 1.23, which is smaller than that observed for CsA. These results suggest that in patients undergoing renal transplantation the same dosing strategies can be applied for CsG as have been established for CsA. PMID- 3347937 TI - Prevention of murine graft-versus-host disease by inducing and eliminating ASGM1+ cells of donor origin. AB - In this study anti-asialo GM1 antibodies (anti-ASGM1) were used to further characterize the effector cells responsible for graft-versus-host (GVH)-induced histopathological lesions: Two different types of ASGM1+ cells were identified: an endogenous ASGM1+ population and an induced ASGM1+ population. Both of the ASGM1+ cell populations exhibited natural killer (NK) cell activity, as assessed by their ability to lyse YAC tumor targets in vitro. Donor C57BL/6 (B6) mice were treated in vivo with anti-ASGM1 to eliminate endogenous ASGM1+ cells. ASGM1+ cells were induced in B6 donor mice by treating the animals with 15 x 10(6) B6 x AF1 (B6AF1) lymphoid cells for 44-48 hr. The induced ASGM1+ cells were eliminated by in vivo treatment with anti-ASGM1. GVH reactions were induced by injecting B6 lymphoid cells into B6AF1 mice. Prior to GVH induction the B6 donor cells were tested for NK cell activity against YAC tumor target cells in vitro and for T and B cell functions by mitogen responses in vitro. GVH reactions were determined by splenomegaly, suppression of the plaque-forming cell (PFC) response to sheep red blood cells (SRBC), suppression of the T and B cell mitogen responses, and the development of GVH-associated histopathological alterations in the thymus, liver, and pancreas. Donor lymphoid cells depleted of endogenous ASGM1+ cells were effective at inducing splenomegaly, severe suppression of immune functions, and histopathological lesions. Donor lymphoid cells depleted of both the endogenous and induced ASGM1+ cells displayed normal T cell mitogen responses and were capable of inducing splenomegaly and partial suppression of the PFC response to SRBC when injected into B6AF1 recipients, however, these lymphoid cells failed to induce both GVH-associated histopathological lesions and severe suppression of T and B cell mitogen responses. These results suggest that semiallogeneic stimulation induces an ASGM1+ population in the donor inoculum that displays NK cell-like function (YAC killing) and that plays a crucial role in inducing GVH mediated histopathological lesions and severe immunosuppression of both T and B cell responses. PMID- 3347938 TI - HLA antigens in ocular tissues. I. In vivo expression in human eyes. AB - The eye is a common site for autoimmune inflammatory diseases, many of which are linked to HLA antigens. The role of these HLA phenotypes in the disease process is presently unknown. In view of the importance of HLA antigens to immune responses, a knowledge of the distribution of HLA antigens in ocular tissues may aid in our understanding of the role of these antigens in disease production or susceptibility. Apart from the cornea, the expression of HLA antigens in human ocular tissues has not been thoroughly investigated. In this study we examined the in vivo expression of HLA antigens in postmortem human eyes using immunohistochemical techniques. The majority of ocular cells were found not to express class I or class II HLA antigens, with the exception of the blood vessel endothelium, which was uniformly class I-positive. The significance of these results is discussed in relation to ocular immunity. PMID- 3347939 TI - Pharmacokinetic profile of cyclosporine A and G and their effects on cellular immunity and glucose tolerance in male and female Wistar rats. AB - This study examined the effects of the widely used immunosuppressor cyclosporine A and of one of its derivatives, cyclosporine G, on glucose tolerance, cellular immunity, and renal and hepatic function, in relation to their pharmacokinetic profile in Wistar rats. After 3 weeks of daily cyclosporine A doses of 10 mg/kg body weight plasma cyclosporine levels were higher in male than in female rats. This was associated in male rats with marked decrease in lymphocyte subsets, affecting particularly the OX19+ T cells, with glucose intolerance, and an increase in plasma creatinine. The female rats had none of these effects. After 3 weeks of daily cyclosporine G doses of 10 mg/kg body weight, plasma cyclosporine levels were higher in male than female animals, and higher than with cyclosporine A in both sexes. Similar cellular immune effects and glucose intolerance were seen in male rats, but of a lesser magnitude than with cyclosporine A. No increase in creatinine was seen, but rats of both sexes treated with cyclosporine G had elevated plasma bilirubin. We conclude that (1) both cyclosporine A and G can cause glucose intolerance, (2) the cyclosporine plasma levels are higher in male than in female rats and with cyclosporine G than with cyclosporine A, for the same oral dose, (3) the absence of glucose intolerance, nephrotoxicity, and cellular immune changes in female rats treated with cyclosporine A is related to their lower cyclosporine levels, and (4) cyclosporine G is less nephrotoxic than cyclosporine A, but more hepatotoxic. PMID- 3347940 TI - Pronounced depressed ability of DNA repair in uremic human lymphocytes. PMID- 3347941 TI - Growth of transplanted tumors in cyclosporine-treated normal recipients. PMID- 3347942 TI - Public aspects of transplantation. PMID- 3347943 TI - Organ procurement in Western Europe. PMID- 3347945 TI - Cultural, ethical, and religious aspects of transplantation. PMID- 3347944 TI - Ethical issues in organ allocation. PMID- 3347946 TI - Organ transplantation, medical ethics, and Jewish law. PMID- 3347947 TI - Religious obstacles and warrants for the donation of body parts. PMID- 3347948 TI - Islamic views on organ transplantation. PMID- 3347950 TI - Immunosuppression: Cyclosporine. PMID- 3347949 TI - Specific allogeneic unresponsiveness. PMID- 3347952 TI - Immunosuppression: monoclonal antibodies. PMID- 3347951 TI - Immunosuppression: deoxyspergualin. PMID- 3347954 TI - Immunomodulation: blood transfusions. PMID- 3347953 TI - Immunosuppression and neoplasia. PMID- 3347955 TI - Immunomodulation: other approaches. PMID- 3347956 TI - Transplantation biology. PMID- 3347957 TI - Kidney transplantation: variations in immunosuppressive therapy. PMID- 3347958 TI - Prolactin as a hepatotrophic hormone. PMID- 3347959 TI - Degenerative changes in fresh aortic root homografts in a canine model: evidence of an immunologic influence. PMID- 3347960 TI - Homotransplantation of testis: experimental study and clinical practice (13 case reports). PMID- 3347962 TI - Cell membrane damage by ultrasound at different cell concentrations. AB - Cell membrane damage by ultrasound was studied in human nucleated cells in vitro at various concentrations. Suspensions of human blood cells, cells of a human leukemic cell line (Reh) and mixtures of nucleated cells with erythrocytes were exposed to continuous ultrasound of 782 kHz at a SPTA intensity of 15 W/cm2. The surviving nucleated cells without membrane damage were counted on the basis of exclusion of ethidium bromide using a flow cytometer. At high cell concentrations as present in whole blood, we observed no cell death, whereas below 5 X 10(7) cells/ml most of the granulocytes, stimulated lymphocytes and Reh cells were damaged. The concentration threshold below which cells were damaged seemed not to depend on the size of the cells, rather on the concentration of particles in the suspension. PMID- 3347961 TI - Evaluation of intracellular energy status during liver preservation by 31P-NMR spectroscopy. PMID- 3347963 TI - Ultrasound attenuation estimation using the LMSE filters and the median filter. AB - The ultrasound attenuation coefficient in known to increase with frequency in soft biological tissue within the diagnostic frequency range. The frequency dependent attenuation coefficient is an important parameter in clinical tissue characterization, especially in liver, and in ultrasonic quantitative B-scan imaging. But, because of the random spatial variation in the backscattered signal amplitude, the estimator variance becomes very large, making it difficult to estimate the attenuation slope from the backscattered ultrasound signal. In this paper we suggest a new ultrasound attenuation estimator based on the calibrated log spectral difference. The proposed estimation process consists of Wiener filtering, Kalman filtering, and median filtering in this order. The simulation results and experimental results with tissue equivalent (TE) phantoms show that combination of the above filterings yields a considerably reduced estimator variance compared with the conventional estimators. PMID- 3347964 TI - Biological effects of shock waves: kidney damage by shock waves in dogs--dose dependence. AB - The effect of shock waves on normal canine kidneys was examined in three groups of dogs whose right kidneys were exposed to 500, 1500, or 3000 shock waves. Autopsy was performed 24-30 h later. The kidneys were enlarged with haemorrhages in the outer and inner renal capsule and intraparenchymally. Macroscopically intraparenchymal haemorrhages were restricted to the high pressure field of the shock wave and consisted of haematomas up to 18 mm diameter (most frequently 6 mm or less) and diffuse haemorrhages. Histologically, haemorrhages were shown to originate from interlobular and arcuate veins. Venous thrombosis, tubular dilatation, and diffuse interstitial haemorrhage occurred in the same area. The number of haematomas was larger, and diffuse haemorrhages were more extended after the application of 1500 and 3000 than after 500 shock waves. No difference was seen between 1500 and 3000 shock waves. PMID- 3347965 TI - Measurement of ultrasonic nonlinear parameter in excised fat tissues. AB - This paper reports sound speed co, adiabatic acoustic nonlinear parameter B/A, and isothermal nonlinear parameter (B/A)' of 33 samples of excised human and animal fats and some simple mixtures, e.g., skim milk and powdered milk. Tissues were obtained from different parts of the body and the measurements were made in the temperature range of 20 degrees C to 37 degrees C. All the fats were highly nonlinear. Although there was a considerable overlap in the values of acoustic nonlinearity of different body fats, in general their values followed the order: mesenteric fat greater than subcutaneous fat greater than omentum fat greater than breast fat. Temperature coefficients of co and B/A, and the difference between adiabatic and isothermal nonlinearity, correlated highly with water/fat content of tissues. A reciprocal relationship between B/A and co, similar to that proposed for liquids, was observed for soft tissues but not for solutions of powdered milk in skim milk. No significant correlation was observed between acoustic measurements and the age of human subjects from which fat tissues were obtained. PMID- 3347966 TI - Doppler measurement of maternal-fetal hemodynamics. PMID- 3347968 TI - Is radical cystectomy indicated in patients with regional lymphatic metastases? AB - The records of 21 patients who had radical cystectomies for the treatment of locally advanced bladder cancer and were found to have regional lymphatic metastases have been reviewed. Ten of these patients had only one lymph node involved (N1), and 11 patients had metastases in more than one lymph node (N2-3). Four patients with N1 disease and 1 patient with N2-3 disease survived tumor-free greater than forty months postoperatively. Radical cystectomy can produce long term disease-free survival in some patients with limited pelvic metastases. PMID- 3347967 TI - Radical prostatectomy. Patterns of local failure and survival in 67 patients. AB - Sixty-seven patients with localized carcinoma of the prostate were treated by radical prostatectomy unaided by adjunctive hormonal therapy. Seven patients (10%) have been lost to follow-up, and 13 patients (19%) have died of other causes without evidence of prostate cancer. The crude or direct survival free of disease for traced patients with clinical Stage B1 nodules (11) and clinical B2 lesions (20) followed for at least fifteen years is 36 per cent and 25 per cent, respectively; the crude or direct survival free of disease for pathologic B (29) and C (12) tumors followed for fifteen years is 31 per cent and 8 per cent, respectively. The local failure incidence at fifteen years for pathologic Stage B tumors is 17 per cent and for pathologic C tumors 31 per cent. Capsular invasion alone on histologic examination did not increase the rate of local or distant failure above that noted for tumors that were entirely intracapsular. However, seminal vesicle invasion is associated with a 44 per cent local failure and 66 per cent distant failure rate. The interval between radical prostatectomy and first failure averaged sixty-nine months (median 56 months) and with hormonal therapy the interval between first failure and death averaged seventy months (median 62 months). The patients who underwent radical prostatectomy in this series represent 22 per cent of the 318 patients presenting with localized prostate cancer between 1960 and 1974. A 1.5-cm nodule was found in 5.5 per cent of the presenting population, and all but one of these patients were treated by radical prostatectomy. PMID- 3347969 TI - Endometrioid carcinoma of prostate. AB - A prostatic tumor that was excised from a sixty-two-year-old man was found histologically to resemble papillary endometrial carcinoma. A specimen of this prostatic endometrioid carcinoma tested positive for prostate-specific antigen and focally positive for mucin, confirming the prostatic epithelial origin of the tumor. A review of the literature indicates that tumors of this type are best approached as a standard acinar adenocarcinoma of the prostate. PMID- 3347970 TI - Blunt bladder trauma: manifestation of severe injury. AB - Twenty-nine patients with bladder injuries requiring operative treatment as a result of blunt trauma are presented. Motor vehicle accidents accounted for 86 per cent of the injuries. Hypotension and gross hematuria were the most prevalent clinical features, 68 per cent and 97 per cent, respectively. All patients had multiple associated injuries requiring operative treatment, average 2.9 per patient. Pelvic fractures occurred in 93 per cent and intra-abdominal injuries in 48 per cent of patients. The majority of ruptures (72%) were intraperitoneal. Mortality, related to associated injuries, was high (34%), attesting to the magnitude of injury sustained by the victim. PMID- 3347971 TI - The Sturgeon Vas Cautery: the first 600 cases. AB - The Sturgeon Vas Cautery, an inexpensive, reusable battery-powered modular unit, has been used in 600 consecutive successful vasectomies with a minimum of complications and without equipment breakdown. PMID- 3347972 TI - Balloon dilatation of urethral strictures. AB - Balloon dilatation of the urethra in 9 male patients with either post inflammatory or post-traumatic strictures was successfully performed. This procedure is primarily indicated in those patients with unsatisfactory results using conventional dilatation with metal sounds. A flexible endoscope was used for guide wire passage and fluoroscopic guidance for positioning the balloon and assuring complete dilatation of the urethral strictures or vesical neck contracture. In this manner, dilatation to 36 F can be performed in a relatively atraumatic manner with minimal discomfort. PMID- 3347973 TI - Surgical correction of external genitalia and lower genitourinary tract of markedly virilized child. AB - Three children who were seen with marked androgenization, including clitoromegaly, labial fusion, and absent vaginal introitus are presented. In each, the vagina was found to be entering at the level of the posterior urethra. Vaginoplasty was performed in each child utilizing a transperineal "pull through" technique. Reduction clitoroplasty was performed in 1 patient. The advantages and optimal timing of these techniques are discussed. PMID- 3347974 TI - Laser vasovasostomy. A comparative retrospective study, using bioquantum microsurgical carbon dioxide laser. AB - Microsurgical carbon dioxide (CO2) vasovasostomy was successfully achieved by fusion coagulation of protein with power densities of 40 W/cm2. When 20 and 32 W/cm2 were used, the histologic picture was found to be a uniform leakage of sperm with secondary granuloma formation, suggesting that at this power density, unsuccessful attempts at welding the vas deferens will result. PMID- 3347975 TI - Suppurative inflammation of vas deferens: an unusual groin mass. AB - We report a case of suppurative vasitis that presented as an inguinal mass in a young man. Inflammation of the vas deferens may occur as a manifestation of genital tuberculosis or other genitourinary tract infection. A granulomatous vasitis, vasitis nodosa, is usually associated with previous trauma or surgery. Suppuration is rare. We report a case that represents a rare cause of an inguinal mass. PMID- 3347976 TI - Vas deferens stones. AB - Reported is a case of stones in the vas deferens that was managed by excision of a segment of the vas. PMID- 3347977 TI - Occult primary seminoma: eighteen-year delay in presentation. AB - Primary retroperitoneal seminoma is well documented. A case is reported in which a patient presented with a seminoma of testis eighteen years after removal of a retroperitoneal seminoma. Histologic appearance of the testis was identified to the original pathology, and it is proposed that this represents recurrence of an occult testicular seminoma. PMID- 3347978 TI - Cytologic diagnosis of prostatic carcinoma by fine-needle aspiration biopsy. Community hospital experience. AB - Transrectal fine-needle aspiration and transrectal or perineal core biopsies were simultaneously performed on 31 patients with suspected prostatic cancer over an eighteen-month period. Of the 29 aspirations that were adequate for cytologic diagnosis, there was histologic correlation in 24 (83%). The sensitivity of aspiration for the diagnosis for prostatic cancer was 92 per cent (11 of 12) compared with 85 per cent (11 of 13) for the core biopsy method. There were no apparent false negative or false positive diagnoses with the aspiration biopsy technique. Insufficient material was obtained by aspiration in 2 cases. A febrile urinary tract infection occurred in 1 patient after transrectal aspiration and core biopsy. Our results suggest that fine-needle aspiration may be utilized by the practicing urologist in conjunction with a pathologist trained in the interpretation of fine-needle aspirates as a safe, relatively inexpensive, and sensitive diagnostic procedure for suspected prostatic cancer. PMID- 3347979 TI - Pharmacoangiographic assessment of penile arteries in patients with erectile failure. AB - Pudendal angiography was done before and thirty minutes after intracavernous administration of 6 mg phenoxybenzamine in 8 men in whom screening with ultrasound Doppler had revealed abnormalities of the penile blood flow. Five vessels were not visualized until phenoxybenzamine was given. Four vessels displayed marked dilatation, three had moderate and one had slight dilatation after the pharmacologic erection was provoked. The method appears to be of value to increase the quality of the angiographic examination. PMID- 3347980 TI - Urinary incontinence during orgasm. AB - Urinary incontinence occurring during orgasm in women is an infrequently volunteered symptom. We studied 3 such patients to understand the mechanism behind such leakage. Urodynamic studies were performed prior to and during orgasm. It was found that during orgasm, there was involuntary bladder contraction with simultaneous urethral relaxation, resulting in leakage. Similar studies performed prior to orgasm did not reveal any involuntary bladder contraction. We believe that incontinence during orgasm is multifactorial: the most important causes are sphincter incompetence, neuropathic hyperreflexic bladder, and non-neuropathic idiopathic bladder instability. PMID- 3347981 TI - Semantics in the field of impotence. PMID- 3347982 TI - Inadequate documentation of apparent renal oncocytoma with metastases. PMID- 3347983 TI - Urologic considerations in treating superficial bladder cancer. Symposium. October 17, 1987, Bermuda. Proceedings. PMID- 3347984 TI - Effect of temperature on transovarial transmission of Babesia bigemina (Smith and Kilborne, 1893) in Boophilus annulatus (Say, 1821). AB - The effect of the temperature on the transovarial passage of Babesia bigemina has been studied in female Boophilus annulatus during their oviposition. Kinetes of Babesia were present in eggs laid at the temperatures of 16, 20, 26, 28, 30 and 35 degrees C. The rate of infection was temperature dependent. It reached at least 50%, even at low temperatures. The average infection level at 26 and 30 degrees C was 270 kinetes per egg. However, between 20 and 35 degrees C the eggs laid during the first 3 days were parasite free. At 16 degrees C, no kinetes were detected during the first 13 days of oviposition. PMID- 3347985 TI - The efficacy of praziquantel (Droncit R) against Raillietina tetragona (Molin, 1958) in domestic fowl. AB - The efficacy of different dose rates of Praziquantel (Droncit R) in tablet and liquid (injectable) form against Raillietina tetragona in the domestic fowl was studied. A dose of 10 mg kg-1 of Praziquantel in tablet form and 0.15 ml kg-1 in liquid form was found to be effective against R. tetragona infection irrespective of age, sex and intensity of infestation of the host. Intramuscular (IM) administration of liquid Praziquantel was found to be more effective than subcutaneous (SC) administration. Susceptibility of the parasite to this drug increased with age. PMID- 3347986 TI - Efficacy and safety of albendazole against experimentally induced Fasciola hepatica infections in goats. AB - Forty 8-week-old goats were allocated to five groups of equal size to determine the optimal dosage of albendazole against experimentally induced 14-week-old Fasciola hepatica infections. Albendazole suspension given orally at 5.0, 7.5, 10.0 and 15 mg kg-1 of body weight was 73.3, 88.2, 88.3 and 95.9% effective, respectively, when compared to untreated controls. Mean number of F. hepatica in the untreated control goats was 75.4. No signs of toxicity were observed. When albendazole was given to eight, 8-week-old goats orally at 75 mg kg-1 (five times the optimal dosage), no signs of toxicity were observed. PMID- 3347987 TI - Efficacy of a fenbendazole-triclabendazole combination against Fasciola hepatica and gastrointestinal nematodes in sheep. AB - A fenbendazole and triclabendazole combination was tested against experimentally induced 6-and 14-week-old infections of Fasciola hepatica and naturally acquired infections of gastrointestinal nematodes in sheep. Forty-eight sheep were divided randomly into six treatment groups of eight animals each. At 7.5 and 10.0 mg kg-1 body weight (BW) (3.75 and 5.0 mg kg-1 BW of each drug), the drug combination was 98.3 and 99.7% effective against 6-week-old F. hepatica infections, and 100 and 99.9% effective against 14-week-old infections. At the same drug dosages, the drug combination was effective against naturally acquired adult Ostertagia spp. (97.3-100%) and adult Nematodirus spp. (90.3-99.9%). No adverse effects associated with treatment were noted. PMID- 3347988 TI - Climate and the distribution of intestinal Trichostrongylus spp. of sheep. AB - The relative prevalences of Trichostrongylus vitrinus, T. colubriformis and T. rugatus in sheep in south-west Western Australia were examined for evidence of associations with climatic conditions in different localities. The region has a mediterranean-type climate with hot, dry summers and cool, wet winters. The intestinal Trichostrongylus spp. populations in sheep sampled comprised 50% T. vitrinus, 38% T. colubriformis and 12% T. rugatus. The prevalence of T. vitrinus was negatively correlated with mean autumn, winter and spring temperatures of a locality. The prevalence of T. colubriformis was positively correlated with mean autumn, winter and spring temperatures. The prevalence of T. rugatus was not correlated with temperature of any season, but was negatively correlated with mean annual rainfall and length of growing season of a locality. There were suggestions of association of amount of rainfall of a locality and prevalence of T. rugatus was not correlated with temperature of any season, but was negatively correlated with mean annual rainfall and length of growing season of a locality. There were suggestions of association of amount of rainfall of a locality and prevalence of T. colubriformis and of differences in seasonal prevalence of T. vitrinus, but the significance of these was obscured by confounding of some climatic factors. The differences in prevalence of the three Trichostrongylus spp. at different locations was attributed to differences in preferred ambient conditions for development and survival of the free-living stages. PMID- 3347989 TI - Development of free-living stages of equine strongyles in faeces on pasture in a tropical environment. AB - The development of the free-living stages and yields of infective third stage strongyle larvae in faeces from a horse with a mixed natural infection deposited on pasture plots were studied over a 2-year period in a coastal area in tropical north Queensland. Two sets of faecal masses (one exposed to, and the other protected from the action of a natural population of dung beetles) were deposited monthly and after 7 days faecal samples were taken for larval recovery and counts. Hatching and development of the free-living stages occurred in faeces on pasture throughout the year. Development was rapid as infective stages were reached within a week of faecal deposition in all months. Yields of infective larvae were affected by the season and the action of dung beetles on the faecal masses. Highest yields were obtained from both beetle-exposed and protected faeces during winter (June to August) and lowest yields were in spring (September to November). High temperatures in spring and summer resulted in low yields of larvae, however, the dry conditions in spring made this season the most unfavourable period. In autumn and winter the temperatures were never low enough to stop or markedly slow down the rate of development, and allowed the development of large numbers of infective larvae. Dung beetle activity was observed throughout the year, and exposed faeces were usually completely dispersed within 24 h of deposition. This resulted in lower yields of infective larvae from these than from protected faeces. Though larval yields were lower, the actual numbers were still substantial so as to cast doubt on the usefulness of these beetles as biological control agents for equine strongylosis in the dry tropics. PMID- 3347990 TI - Natural infection of land-snails by protostrongylids on a pasture grazed by sheep in the Rabat area of Morocco. AB - The output by sheep of first-stage protostrongylid larvae, and the population density and level of infection of terrestrial molluscs were assessed monthly during a 1-year study. Limax maximus was the most infected mollusc. Juveniles were less infected than adults, for Cernuella virgata and Theba pisana; the reverse was observed for Otala lactea. Banded individuals had a lower intensity of infection than the non-banded ones for C. virgata and T. pisana. Sixty-one percent of protostrongylid larvae in molluscs on the pastures studied were found in C. virgata, and 25% in O. lactea. The infectivity of the pasture for sheep was related to rainfall. PMID- 3347991 TI - Anthelmintic activity of continuous low doses of fenbendazole into the rumen of sheep. AB - Fenbendazole (FBZ) was continuously infused for 30 days into the rumen of 103 lambs which had mature or developing benzimidazole-susceptible or thiabendazole resistant Haemonchus contortus and susceptible Trichostrongylus colubriformis infections. Ovicidal, larvicidal and adulticidal activities were exhibited against benzimidazole-susceptible and benzimidazole-resistant H. contortus worms by FBZ at a dose level of greater than or equal to 0.2 mg kg-1 body weight day-1. Reasonably consistent high level efficacy against H. contortus was obtained with dose levels greater than 0.4 mg kg-1. Excellent control of susceptible T. colubriformis worms was achieved with the lowest dose tested of 0.4 mg kg-1 day 1. The intraruminal infusion critical study method is a tool to determine the feasibility of incorporating a candidate anthelmintic compound in a continuous sustained-release rumen device formulation. The anthelmintic profile of FBZ obtained by low-level intraruminal administration suggests that it would be a potential candidate. PMID- 3347992 TI - Interactions between the predacious fungus Arthrobotrys oligospora and third stage larvae of a series of animal-parasitic nematodes. AB - Interactions between the predacious hyphomycete Arthrobotrys oligospora and third stage larvae of nine animal-parasitic nematodes were tested in vitro. The trap inducing capabilities of the ruminant trichostrongylus Cooperia oncophora, C. curticei, Haemonchus contortus and Ostertagia ostertagi and of equine cyathostomes were almost comparable to those of free-living soil nematodes, and significantly higher than those of the porcine Oesophagostomum dentatum and Oe. quadrispinulatum and of the murine Nematospiroides dubius. The trap-forming potential of Dictyocaulus viviparus was poor. All animal-parasitic nematodes were rapidly captured when fungal traps had been pre-induced in high numbers. The possible influence of predacious fungi on animal-parasitic nematode populations under natural conditions in the field is discussed. PMID- 3347993 TI - Environmental contamination by eggs of Toxocara species. AB - A study was conducted to determine the level of contamination with Toxocara spp. eggs in parks and playgrounds in several central Illinois communities. A total of 135 composite 50-g soil samples were collected from 23 parks and public places in three cities in central Illinois. Of these soil samples, 22 (16.3%) contained from one to thirteen Toxocara spp. eggs. A total of 40 fecal samples were collected from the same parks. Toxocara spp. eggs were found in two (5%) of the samples. PMID- 3347994 TI - Ascaris suum antigens incorporated into liposomes used to stimulate protection to migrating larvae. AB - Four- to 8-week-old SPF pigs were immunized, using antigens of Ascaris suum incorporated into liposomes, via intestinal cannula or orally. Avridine was also incorporated in the liposomes in one experiment and interleukin-2 (IL-2) injected into pigs in another experiment. A priming dose of embryonate eggs (80-470 eggs/pig) were given in four of six experiments. Compared to control animals, the greatest protection of pigs to migrating ascarid larvae from a challenge dose of 10,000 embryonated eggs occurred where pigs received (1) a priming dose of eggs plus second-stage ascarid larval wall incorporated into liposomes, with or without avridine or IL-2, or (2) a priming dose of eggs plus ascarid intestinal aminopeptidase incorporated into liposomes with IL-2. The degree of protection was not statistically significant due, in part, to the variability in the responses of animals in the same treatment groups and the small number of animals per group. In general, only low titers of specific serum antibodies were detected and specific antibodies were not detected in the intestinal washing. PMID- 3347995 TI - The duck hepatitis B virus DNA polymerase is tightly associated with the viral core structure and unable to switch to an exogenous template. AB - The duck hepatitis B virus (DHBV) has a DNA polymerase associated with it which uses the incomplete viral genome as endogenous template. A prerequisite for studying this polymerase is the availability of conditions to open viral cores without destroying their enzymatic activity. In this study, this was achieved by a brief treatment with low pH. DHBV DNA in low-pH-treated cores was susceptible to digestion with deoxyribonuclease I and restriction enzymes, and large restriction fragments diffused out of the viral cores. However, the DHBV polymerase remained tightly associated with its DNA template in the viral core structure and could still incorporate nucleotides into those DNA fragments which carried the DNA-bound protein and remained in the core. The DHBV polymerase could not switch to any of several exogenously supplied templates although these were most likely accessible to it. The manner in which this tight association of the DHBV polymerase with the core may occur, and the possible implications of this interaction during the DHBV replication cycle, is discussed. PMID- 3347996 TI - Stability of vaccinia virus DNA during persistent infections: accumulation of left-end deletions and of tandem repeats at both ends of the viral genome and prevention by interferon. AB - The stability of the large vaccinia virus genome (122 MDa) has been studied in long-term cultures of persistently infected Friend erythroleukemia (FEL) cells. Deletions of about 8 MDa at the left terminus of vaccinia DNA are generated at early passages, and are maintained even after 2 years of continuous cell passages. The generation of deletions is followed by a stable accumulation of tandem repeats up to 6 MDa at the left end and up to 2 MDa at the right end of vaccinia DNA. Neither translocations nor rearrangements of DNA are observed during persistent infection. A recombinational mechanism within the tandem repeats or a mechanism similar to that described for adenovirus might explain the reiteration of tandem repeats at both ends. Significantly, in persistently infected cultures continuously treated with interferon (IFN) both the deletion and the large accumulation of tandem repeats were completely blocked. We suggest that reiteration of tandem repeats at the termini of vaccinia DNA might provide signals for more efficient virus multiplication in FEL cells. PMID- 3347998 TI - Effect of actinomycin D on tobacco mosaic virus (TMV) accumulation in isolated tobacco protoplasts under varying light conditions. AB - The effect on Tobacco mosaic virus (TMV) accumulation of actinomycin D (AMD) introduced shortly after inoculation into isolated tobacco protoplasts under varying light conditions was examined. The emission spectrum of the light source contained lines in the visible range and in the ultraviolet band (300-400 nm). AMD absorbed light in the visible (400-500 nm) and in the uv (200-400 nm) ranges. AMD substantially inhibited TMV multiplication in the light, and also when the protoplasts were incubated in petri dishes covered with a black filter that allowed only uv light in the range 260-390 nm to pass. In the dark, and also in petri dishes covered with blue or yellow filters that passed in the ranges 400 500 or 500-600 nm, respectively, AMD stimulated TMV reproduction. The suppression of TMV multiplication in isolated tobacco protoplasts was assumed to be associated with a photodynamic effect caused by absorption of uv light by AMD. PMID- 3347997 TI - Nucleotide sequence of the middle dsRNA segment of bacteriophage phi 6: placement of the genes of membrane-associated proteins. AB - The genome of the lipid-containing bacteriophage phi 6 contains three segments of double-stranded RNA. We have determined the nucleotide sequence of cDNA derived from the middle-size RNA segment. The coding sequences of three proteins on this segment were identified on the basis of size and the correlation of predicted N terminal amino acid sequences with those found through the analysis of isolated proteins. In contrast to our results with the small phi 6 dsRNA segment, the open reading frames are not tightly clustered. The homologous terminal noncoding regions between the middle and small dsRNA segments are found to be more extensive than RNA sequencing had previously indicated. PMID- 3347999 TI - SVLM21, a mutant of Sindbis virus able to grow in Aedes albopictus cells in the absence of methionine, shows increased sensitivity to S-adenosylhomocysteine hydrolase inhibitors such as neplanocin A. AB - Inhibition of S-adenosylhomocysteine (AdoHcy) hydrolase by compounds such as Neplanocin A (NPA) leads to the build-up of AdoHcy and the inhibition of methyltransferase enzymes. Whether assayed by efficiency of plaquing or virus yield, SVLM21, a mutant of Sindbis virus resistant to methionine deprivation, was more sensitive to NPA than was the standard virus (SVstd) from which it was derived. For example, whereas 10 micrograms NPA/ml depressed the yield of SVLM21 by more than 30-fold, the yield of SVstd was not significantly affected. Similar differences in sensitivities were shown to three other compounds which inhibit AdoHcy hydrolase. These results support the idea that SVLM21 codes for an altered RNA methyltransferase. PMID- 3348000 TI - Characterization of a nonhemagglutinating mutant of canine parvovirus. AB - A nonhemagglutinating mutant of a 1978 isolate of canine parvovirus (CPV) was derived after repeated passages in the NLFK feline kidney cell line. The mutant CPV was antigenically indistinguishable from wild-type virus when tested with 82 monoclonal antibodies, and it replicated in cat and dog cell lines in culture. Sequences of the VP-1 and VP-2 genes revealed two nucleotide and two predicted amino acid sequence differences at 77 and 88 genome map units in the mutant compared to hemagglutinating viruses. One or both of those two mutations must determine the difference in the ability of the virus to agglutinate erythrocytes. PMID- 3348001 TI - Characterization of hepatitis B virus X gene: in vitro translation of mRNA from COS-1 cells transfected with the X gene. AB - To elucidate the biological role of the X region of HBV DNA, we constructed an expression plasmid pSV2HBx by inserting the StuI/BglII fragment of HBV DNA into the pSV2 vector. Although X region products were not identified in vivo in transfected COS-1 cells, transcripts were translated in vitro and a 17-k Da protein was immunoprecipitated with an antibody raised against a synthetic peptide corresponding to the carboxy terminus of the X region open reading frame. Among 68 HBV carrier sera tested, two were found to contain antibodies reactive to the in vitro translation product. These results suggest that the X region is a gene which can be actually expressed at some stage of HBV infection. PMID- 3348002 TI - Is the gene pool of influenza viruses in shorebirds and gulls different from that in wild ducks? AB - Evidence is presented for a second major gene pool of influenza A viruses in nature. Shorebirds and gulls harbor influenza viruses when sampled in the spring and fall. Approximately half of the viruses isolated have the potential to infect ducks but the remainder do not. The hemagglutinin subtypes that are prevalent in wild ducks were rare or absent in shorebirds and gulls. PMID- 3348003 TI - Antibody-mediated binding of a murine ecotropic Moloney retroviral vector to human cells allows internalization but not the establishment of the proviral state. AB - We have attempted to introduce a neomycin-resistance gene, recombined in a murine (ecotropic) Moloney retrovirus, into HEp2 human cells which are resistant to infection by this retrovirus. To allow the binding of the retroviral vector on HEp2 cells, we have tested several antibody constructions between two monoclonal antibodies, one (mAb 5E9) directed against the human transferrin receptor and the other (mAb 615) directed against the gp70 envelope viral protein. The crosslinking of mAbs 5E9 and 615 by a sheep anti-murine kappa light chain antibody allowed the binding of virus on HEp2 cells. After incubation at 37 degrees, virus was internalized by HEp2 cells. However, no neomycin-resistant colonies of HEp2 cells have been obtained under various conditions. Our results suggest that binding and internalization of a retrovirus are not sufficient for establishment of the proviral state in cells which do not express a specific receptor. PMID- 3348004 TI - [Planning of research studies in the field of oncology]. PMID- 3348005 TI - [Prognosis in fibrosarcoma of bone]. AB - A retrospective study of 42 patients with bone fibrosarcoma was carried out. A new highly informative index--tumor growth rate--is suggested. It is a ratio of tumor maximum diameter to case history length (Rtg = L, CM/t, month). Three histologically-identified grades of fibrosarcoma malignity are discussed. They are based on the variation in metastasis development and survival rates. As a result of mathematical treatment of the findings, 8 characteristics of bone fibrosarcoma were identified which influenced prognosis. A multi-factorial analysis of the data was undertaken using said characteristics. Indexes were calculated for each characteristic and tabulated to prognosticate 3-year survival of patients with fibrosarcoma of the bone. PMID- 3348006 TI - [Rate of growth of primary cancer of the breast]. AB - Repeated mammography was used to study the rate of primary tumor growth in 64 cases of breast cancer. Primary tumor size doubling time varied 2.9-459 days (98.7 +/- 10.9 days on the average). Four patterns of tumor growth rate were identified: (1) very swift (average doubling time--20.2 days)--in 20.2% of patients; (2) rapid (average doubling time--59.2 days)--37.5% (3) moderate (average doubling time--91.2 days)--14.1%, and (4) slow (average doubling time- 212.5 days)--28.1%. PMID- 3348007 TI - [Single preoperative radiation and short-wave treatment of breast cancer]. AB - A total of 93 patients were assigned to receive either radiation treatment alone (group 1) or in combination with local microwave-induced hyperthermia (group 2) prior to mastectomy. The treatment results were compared. Within a two-year follow-up period, all patients of group 2 remained free of relapse, metastases being registered in 2 (6.2%) cases. In group 1, relapse was observed in 1 case, whereas metastasis--in 7 (11.5%). The study failed to establish drug-induced tumor pathomorphosis in 12.5% in group 2 and 73.8% in group 1. The procedure did not interfere with surgery, nor was it followed by an increased postoperative complication rate. PMID- 3348008 TI - [Potentialities of an x-ray method of determining malignant changes in polyps of the large intestine]. AB - The study was concerned with evaluation of the clinical and roentgenologic data on 57 cases of malignant polyps of the colon. Malignant polyps reaching 10 mm in length were found. Malignancies were identified using endoscopy and biopsy in 58.6% and X-ray examination--45.8%. Among the most effective methods of X-ray examination of the large bowel for cancer should be: high-voltage roentgenography employing incomplete barium enema, primary double contrast examination, direct blow-up and parietography. X-ray signs of malignant transformation of polyps are: persistent retention of barium, wavy and indistinct contours, irregular pattern, rapid growth of neoplasm, retraction of tumor base and disparity between polyp size and its pedicle length. PMID- 3348009 TI - [Adenocarcinoma of the uterine cervix: characteristics of its pathogenesis, clinical picture and diagnosis]. AB - The paper discusses the data on 262 cases of cervical carcinoma (adenocarcinoma- 138; squamous cell carcinoma--124). The pathogenetic and clinical characteristics, particularly localization, growth and dissemination, of the two malignancies were compared. More than a third of cervical carcinoma patients revealed disturbances in fat and carbohydrate metabolism and ovarian and menstrual function. The endometrium and ovaries were involved in half of them. No such involvement was observed in squamous cell carcinoma patients. Nor any significant disorders occurred in the neuroendocrine system. The hormone dependence of cervical adenocarcinoma and the common nature of its pathogenetic features and those of adenocarcinoma of the endometrium are suggested. PMID- 3348010 TI - [Radiotherapy of patients with stage III Hodgkin's disease using the method of continuous fractionated irradiation]. AB - Clinical rationale for alternating split-course radiotherapy for stage III Hodgkin's disease is discussed. The procedure was employed in 54 such patients. It proved useful in total nodal irradiation for advanced disease, resulting in improved survival. The technique involves a shorter duration of treatment than that of the standard one. PMID- 3348011 TI - [Significance of polyamines for the early diagnosis of spontaneous hemoblastoses in AKR mice]. AB - Polyamines levels were studied in various tissue specimens obtained from high leukemia AKR mice aged 12 months and less. Organ tissues of leukemic animals revealed increased levels of polyamines and changes in their profile. In symptomatic mice, this was matched by relevant morphologic changes. It is inferred that putrescine is a marker of latent leukemia development. PMID- 3348012 TI - [Extension of the length of terms of temporary work incapacity, set by the Medical Expert Commission for Evaluation of Work Capacity, in the case of patients with malignant tumors]. AB - The results of granting temporary disability payments for longer periods were followed in 549 patients with malignant tumors at various sites. It was found that 76-82% of stage I-IIa (T1-2N0M0) cancer patients resume working; working ability is limited in 14-18%. Two-thirds of them need another 2-3 months to complete treatment. To allow such patients to stay out of work is essential for prevention of disability from malignant tumors. PMID- 3348013 TI - [Preliminary results of preoperative regional chemotherapy of cancer of the rectum]. AB - The results of combined treatment for rectal cancer including preoperative intraarterial chemotherapy are discussed. The study group showed a significant decrease in the frequency of local recurrence development, justifying the use of the said combination for treatment of locally-advanced rectal cancer. PMID- 3348015 TI - [Interstitial gamma-therapy of patients with cancer of the mucous membrane of the mouth]. AB - In 1984-1986, interstitial gamma-therapy was used in 57 patients for cancer of the oral cavity (28), tongue (16) and lower lip (13). Complete regression was observed in 44 (77.3%) patients. No severe side effects were registered. The treatment proved less effective in cases of large tumor located in proximal areas of the oral cavity. PMID- 3348014 TI - [Pelvic exenteration as a means of improving the resectability of advanced cancer of the rectum]. AB - The paper discusses the results of treatment of 10 male patients who underwent pelvic evisceration for advanced rectal cancer. Surgical technique is described. In 9 cases, an isolated ileocecal "urinary bladder" was formed; in 1 patient urine was passed into a small intestine segment. The involvement of the urinary bladder and/or the prostate were observed in 6 patients. One patient died shortly after surgery, three--within the first 12 months and another 2--during the second year. Four cases have survived over 5 years, 3 of them surviving over 10 years. PMID- 3348016 TI - [Apropos of the article: "Cost of studies on the carcinogenic effects of chemical compounds in animal experiments"]. PMID- 3348017 TI - How much blood for the world? AB - Based on data from 96, and estimates from 32 countries with populations of over 1 million, it was calculated that the total amount of whole blood collected annually in the world in the early 1980s was about 75 million units. Of this, one third was collected by Red Cross and Red Crescent blood programmes. The index of donations per 1,000 population was on average 50.2 in industrial market countries, 9.5 in middle-income countries and 1.1 in low-income countries. For planning purposes donation rates in relation to health services are better than the population index. It seems that roughly 10 annual donations per acute hospital bed, or 0.40 donation per patient admission to these hospitals would be sufficient to provide adequate quantities of blood and blood products for modern haemotherapy. PMID- 3348018 TI - Use of polyester filters for the preparation of leukocyte-poor platelet concentrates. AB - We studied the usefulness of two polyester leukocyte removal depth filters for the preparation of leukocyte-poor platelet concentrate. The Sepacell R500A removed approximately 92% of the white cells and 98% of the platelets from stored concentrate. In contrast, the Travenol 4C2423 polyester depth microaggregate filter removed less than 1% of the platelets but only 14% of the leukocytes. These findings were obtained with stored (5-day-old) random donor platelets as well as with 16-hour-old platelets collected by apheresis. We conclude that neither of these two leukocyte removal depth filters are suitable for the preparation of leukocyte-poor platelet concentrate; the Sepacell because it removes too many platelets and the 4C2423 because it removes too few leukocytes. The efficiency of cell removal by polyester filters is likely related to alteration of the polyester filter element during fiber manufacture. PMID- 3348020 TI - HIV antibody screening of blood donations in the United Kingdom. AB - Routine screening of blood donations for anti-HIV commenced in the UK during October 1985 and by the end of February 1987 approximately 3.7 million donations had been tested. Seventy-two were confirmed anti-HIV positive, i.e. 0.002%. Of the anti-HIV-positive donors interviewed to date, the majority are young homosexual or bisexual men or intravenous drug abusers. Included in the study are data collected on approximately 470,000 donors giving blood for the first time. Twenty of these have been confirmed anti-HIV positive (0.004%), and 19 interviewed have admitted to being in risk categories. In 5 instances a positive anti-HIV donor was found negative on a previous occasion, and in 1 instance the products from the donation led to seroconversion in the recipients. The majority of anti-HIV-positive donors attending for blood donation did so because they did not consider that the self-exclusion categories specified in the leaflet issued to donors applied to them since homosexual activity or drug abuse was not currently being practised. PMID- 3348019 TI - Extended storage of single-donor apheresis platelets in CLX blood bags: effect of storage on platelet morphology, viability and in vitro function. AB - A CLX (Cutter Laboratories, Berkeley, Calif.) bag system was evaluated for storage of single-donor apheresis platelets collected with the Haemonetics V-50 blood processor. Concentrates (n = 21) containing 3.9-5.2 x 10(11) platelets in 292 (+/- 41.8) ml were stored in two 1-liter bags for 7 days at 22 degrees C. pH was well maintained, declining from an initial pH of 7.0 (+/- 0.04) to 6.92 (+/- 0.20) after 7 days. Platelet morphology, response to a hypotonic stimulus and aggregation induced by paired agonists (epinephrine and ADP, or collagen) were also well-preserved. Concentrates with a wide variation of platelet yields (2.0 greater than or equal to 5.2 x 10(11), n = 43) also maintained pH (6.96 +/- 0.26), morphology and aggregation when stored for 7 days. All platelet concentrates (n = 64) were sterile at collection. Single-donor apheresis platelets may be stored in this bag system for up to 7 days. PMID- 3348021 TI - A rapid and accurate single-drop modification of the acid-elution technique for detecting fetomaternal hemorrhage. AB - A single-drop modification of the acid-elution technique (Kleihauer-Betke) for quantitating fetomaternal hemorrhage is described. It obviates the need for the tedious and time-consuming manual counting of background adult cells. Rather, this is achieved by automated red-blood cell counting of the initial specimen and delivery of a standard volume (1 microliter) of a standard dilution (1:1,000) in the form of a droplet to a microscope slide. The droplet is left to dry undisturbed at room temperature and then stained. The fetal cells are manually counted while the total number of cells is calculated from the initial red-blood cell count, standard volume, and standard dilution. Determinations on 4 different concentrations of fetal/adult red cell mixtures are performed. Results indicate improved accuracy and precision relative to the standard technique in significantly less time for volumes of fetomaternal hemorrhage requiring more than the standard dose of Rho(D)-immune globulin. PMID- 3348022 TI - Zulu XX/XX dispermic chimaera from Natal with two populations of red blood cells and patchy skin pigmentation. AB - The chimaera is female and has two children. Her blood contains 99% group O, type AcP:BA, Pep-A:8-2 and 1% group A2B, type AcP:RA, Pep-A:1 red cells. H-, A- and B transferase activities were demonstrated in her serum. The level of the H enzyme activity is low but is at the lower end of the normal range for group O persons. The levels of the A and B enzymes are also low but are higher than expected in a person with 1% A2B red cells in the blood. The levels of the A and B enzymes indicate that tissues other than the chimaera's haemopoietic tissue carry her genetically A2B cell line and are contributing the corresponding transferases to her plasma. Gross patchy skin pigmentation is present on the upper part of her body. The chimaera has evidently inherited two dissimilar germ nuclei from each parent. PMID- 3348023 TI - Major histocompatibility complex markers in patients with nomifensine-induced immune hemolytic anemia. AB - To evaluate a possible role of major-histocompatibility-complex (MHC)-related immune-response genes for the selective production of drug-induced antibodies, HLA class I (ABC), class II (DR, DQ), class III (BF, C2, C4A, C4B) as well as glyoxalase-1 allotypes were investigated in 26 patients with nomifensine-induced immune hemolytic anemia. No statistically significant deviations of MHC antigen frequencies were noted. The possible implications of these findings are discussed. PMID- 3348024 TI - Outbreak of hepatitis A on an offshore petroleum platform, Alaska. AB - An outbreak of 8 cases of hepatitis A among the 36-member crew of an offshore Alaska petroleum production platform was linked to a previous outbreak in an urban day-care center. Transmission of hepatitis A on the platform related most plausibly to refrigerated food items contaminated by a cook with mild disease. Control efforts included identifying and treating contacts of case patients who had traveled far from the platform before becoming ill. Early serologic confirmation of diagnosed cases and rapid reporting to public health authorities are essential to prevent disease transmission. Timely investigation can limit the administration of immune globulin to persons at high risk of contracting the disease. PMID- 3348025 TI - Perfusion lung scans provide a guide to which patients with apparent primary pulmonary hypertension merit angiography. AB - There is hesitancy, based on the perceived risk, to do pulmonary angiography in patients believed to have primary pulmonary hypertension. Yet pulmonary hypertension due to major-vessel, chronic thromboembolism mimics primary pulmonary hypertension clinically and on standard laboratory tests. Because thromboembolic pulmonary hypertension is potentially remediable by thromboendarterectomy and primary pulmonary hypertension is not, differentiating between these disorders is essential. Angiography is required in patients with thromboembolic pulmonary hypertension to define the anatomic location of the thrombi. In evaluating perfusion lung scans of 110 patients with pulmonary hypertension to determine whether the scan might provide a guide to selecting those patients who merit angiography, no segmentalsize perfusion defects were noted on the scans of 64 patients with primary pulmonary hypertension, whereas all 46 patients with thromboembolic hypertension had one or more defects that were segmental in size or larger. These data indicate that a perfusion lung scan should be done in patients with pulmonary hypertension of uncertain cause and that those with one or more segmental or larger defects merit pulmonary angiography before being diagnosed as having primary pulmonary hypertension. PMID- 3348026 TI - Heterosexual and perinatal transmission of human immunodeficiency virus in a low prevalence community. AB - Six previously unidentified cases of human immunodeficiency virus (HIV) infection were found during an investigation and follow-up of three clusters of heterosexually and perinatally transmitted HIV infections. The investigations were to identify those infected, to interrupt the transmission of HIV, to attempt to reduce the likelihood of the development of the acquired immunodeficiency syndrome among those found to be seropositive, and to show the usefulness of traditional disease control strategies during this epidemic. Our findings indicate the value of contact tracing for HIV infections and the need to provide and evaluate educational activities regarding the transmission of HIV in low prevalence populations. PMID- 3348028 TI - Death and dying--a public or private matter? PMID- 3348027 TI - The clinical significance of water pollution. AB - These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs Homer A. Boushey, Professor of Medicine, and David G. Warnock, Associate Professor of Medicine, under the direction of Dr Lloyd H. Smith, Jr, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143. PMID- 3348029 TI - Cigarette smoking is bad practice. PMID- 3348030 TI - Spontaneous gas gangrene at a site of remote injury--localization due to circulating antitoxin. PMID- 3348031 TI - Severe hypermagnesemia due to multiple-dose cathartic therapy. PMID- 3348032 TI - Occult mineral oil pneumonitis in anorexia nervosa. PMID- 3348033 TI - Coexistent dermatomyositis and autoimmune thyroiditis. PMID- 3348034 TI - Neuromuscular blockade due to gentamicin sulfate. PMID- 3348035 TI - Autopsy on an AIDS patient. PMID- 3348036 TI - Carpal tunnel syndrome. AB - Carpal tunnel syndrome is a common and potentially disabling condition. When suspected, the diagnosis can be readily made on clinical evidence without the the need for extensive ancillary tests. Primary physicians should be able to manage most patients with medical therapy. Patients for whom medical treatment fails or who present with weakness or thenar atrophy should be referred to a competent hand surgeon. Most patients can expect to have a good outcome if the diagnosis is made early, appropriate therapy is instituted, and a periodic reassessment is done to guide further clinical decisions. PMID- 3348037 TI - Training primary care physicians in flexible sigmoidoscopy--performance evaluation of 17,167 procedures. AB - The flexible fiber-optic sigmoidoscope is rapidly replacing the rigid sigmoidoscope in routine screening for colorectal cancer. This study was undertaken to evaluate the safety, usage pattern, and efficacy of fiber-optic sigmoidoscopy by evaluating the outcome of training and the results of procedures carried out by a group of primary care physicians. Of 1,153 participants in one day flexible sigmoidoscopy workshops, 764 (66%) returned questionnaires evaluating their experiences following this training. Of these, 438 physicians had obtained a flexible sigmoidoscope, used it frequently, and had done a total of 17,167 examinations. The average time of scope usage was nine months. Although additional supervised training was suggested at the time of the workshop, 68% of physicians began doing flexible sigmoidoscopy without it. A total of 465 polyps and 153 cancers were detected by the study group for an overall detection rate of 2.7% for polyps and 0.9% for cancers. Four complications were reported. This study indicates that the technique of flexible sigmoidoscopy is readily learned, is diagnostically productive, and is reasonably safe in the hands of primary care physicians. PMID- 3348039 TI - Thoughts on physician-assisted suicide. PMID- 3348038 TI - Impact of urban disaster on a university trauma center. AB - On the eve of the 1984 Summer Olympics, a deranged man drove his car at high speed onto a pedestriancrowded sidewalk in a suburb of Los Angeles. The UCLA Medical Center, located two blocks from the scene, received 17 of 51 casualties. One patient arrived in full cardiac arrest and could not be resuscitated. Six had minor injuries or temporary hysteria and did not require admission to hospital. The mean injury severity score of the 10 patients who were admitted was 13.6 (range 3 to 48). Three patients required immediate surgical procedures, and two had delayed orthopedic operations. Specialty consultations were needed in orthopedics, neurosurgery, plastic surgery, otolaryngology, pediatric surgery, and pediatric intensive care. There were no subsequent deaths, although two patients had substantial residual neurologic disability. This episode of unexpected urban violence underscores the need for dedicated trauma services in university centers. Functions of such services include disaster planning, deploying surgical personnel, managing injured patients, and analyzing outcomes. PMID- 3348040 TI - The duty to protect others from your patients--Tarasoff spreads to the Northwest. AB - The California Supreme Court's Tarasoff decision was the seminal case in the area of the duty to protect third parties from the potential of violence from patients. Tarasoff-related issues have now spread to many jurisdictions in the country. This article will pay particular attention to the cases influencing law in Washington and Oregon and will review the clinical duty to protect others from your patients that existed before Tarasoff, as physicians were taught to work between privilege and civil commitment statutes. The California law designed to limit Tarasoff liability and the reasons why legislators should be willing to support such legislation are discussed. PMID- 3348041 TI - Recombinant alpha-interferon (alpha-IFN) for progressive hairy-cell leukemia (HCL): a study in previously untreated nonsplenectomized patients. AB - Ten nonsplenectomized patients (5 males, 5 females) with hairy-cell leukemia were treated with recombinant alpha-IFN. The median age of patients was 54 years (32 76 years). The time between diagnosis and onset of treatment ranged from 1-120 months. Initially the patients received 5 x 10(6) I.U. daily by intramuscular or subcutaneous injections for 10 weeks. Thereafter the dose of IFN was reduced to 5 x 10(6) I.U. 3 x weekly and after 6 months to 5 x 10(6) I.U. 2 x weekly for at least 6 months. The median time of patient follow-up is 23 months (4-28 months). Three complete remissions were achieved after 3-24 months and five partial remissions after 4-18 months. One patient showed improvement after 3 months, and one patient died from cerebral hemorrhage after 5 weeks. In eight of ten patients peripheral blood cell counts normalized after a median of 7 months (1.5-11 months). A marked reduction in spleen size was observed in all seven patients who had splenomegaly at study entry. Two of three patients who interrupted therapy have relapsed after 2 and 6 months. We conclude that alpha-interferon is an effective method of first-line treatment in patients with HCL. PMID- 3348043 TI - Secretory immunoglobulin A (sIgA) in the serum of cystic fibrosis patients. AB - Clearly increased sIgA values were found in cystic fibrosis patients in more than 70%. The highest concentrations were seen in patients with obstructive liver disease. There were no correlations between sIgA and liver-associated enzymes. Postmortem histology and sIgA correlated well. These data suggest a pertinent role of sIgA assessment in evaluation of hepatic involvement in cystic fibrosis. PMID- 3348042 TI - [Viral nucleic acids in the serum of hepatitis B patients]. AB - Detection of hepatitis B viral DNA (HBV-DNA) is the most reliable test for infectivity of a patient's serum. HBV-DNA was detected by spot hybridization on nylon membrane. HBV-DNA was detected during the first or second week of jaundice in 22/133 (16.5%) sera from patients with acute hepatitis who did not develop chronic disease later on. However, in patients with acute hepatitis who later on developed the chronic form, HBV-DNA was found in 12/12 (100%) cases in the first or second week after onset. In other patients who had chronic hepatitis for longer than one year HBV-DNA was detected in 92/113 (81.4%) sera when HBe antigen was also detectable and in 11/104 (10.6%) when HBe antibodies were found. HBV-DNA was present in 32/38 (84.2%) sera from healthy antigen carriers when HBe antigen was detected and only in 2/173 (1.2%) sera of HBe antibody positive HBs antigen carriers. The highest levels of HBV-DNA were found in patients with chronic hepatitis B infection who were found in patients with chronic hepatitis B infection who were on haemodialysis therapy. Almost all had HBe antigen and HBV DNA was also detectable in 82/84 (97%) sera. 11/28 (39.3%) sera from patients with chronic hepatitis B as well as HIV infection showed HBV-DNA. Detection of HBV-DNA has significantly improved the accuracy of diagnosis of hepatitis B viral infection. PMID- 3348044 TI - Screening for gestational diabetes in central Wisconsin. PMID- 3348045 TI - Rural health initiative nears completion. PMID- 3348047 TI - Voluntary active euthanasia. PMID- 3348046 TI - Children's toys. PMID- 3348048 TI - The economics of the Irish health care system--relevance for nursing. PMID- 3348049 TI - Nurses as health educators. PMID- 3348050 TI - Promotion of continence in the elderly. PMID- 3348051 TI - The joys of liability litigation. PMID- 3348052 TI - Medical Center Hour: teenage pregnancy. PMID- 3348053 TI - Breast hematoma following needle localization: case report. PMID- 3348054 TI - Management of pheochromocytoma in sickle cell disease: case report. PMID- 3348055 TI - Cytologic findings in peritoneal washings associated with benign gynecologic disease. AB - In order to define the problems in the interpretation of peritoneal washing cytology specimens, 149 benign cases were examined retrospectively and the cytologies compared with the correlating histologies. There were problems in the cytologic interpretation on blind review in 18 cases (12.1%). Difficulties in interpretation of peritoneal washing cytology included conditions associated with (1) mesothelial reactions and adhesion formation, (2) rupture of cystic structures, (3) fallopian tube epithelium and (4) combinations of these factors. It is anticipated that familiarity with these problems will enhance accuracy in peritoneal washing cytology, particularly in those cases in which a malignancy is present but has not penetrated into the peritoneal cavity. PMID- 3348057 TI - Cervicovaginal and endometrial cytology in ovarian cancer. AB - The clinical significance of cytologic examination was studied in 114 patients with ovarian cancer who had received preoperative cytologic examinations. The overall positive rate of the cytologic examinations was 26.3% (30 of 114): 22 (19.3%) of the 114 cases had positive cervicovaginal smears while 13 of 31 endometrial aspiration smears (41.9%) were positive. The positive rate was not related to the volume of ascites but rather to its presence or absence. Thus, if ascites was observed, the positive rate was about 2.1 times higher than if it was absent. In two of four cases of ovarian cancer with no endometrial invasion but a positive cytologic examination of ascitic fluid, fallopian tube specimens contained cancer cells; this suggests that ovarian cancer cells may reach the cervix and/or vagina by passing through the fallopian tube, particularly if ascites is present. Since cytologic examination, especially of endometrial aspiration smears, shows a high positive rate if ovarian cancer cells are observed in the abdominal cavity, cytology should be used as an important ancillary method for the assessment of ovarian cancer. PMID- 3348056 TI - Nonspecific esterase activity of human alveolar macrophages in routine cytology. AB - Alpha-naphthyl acetate esterase (ANAE) activity in alveolar macrophages was demonstrated in air-dried smears from samples of 82 sputa, 47 bronchial secretions and 14 bronchial lavages from 113 patients. Enzyme activity was estimated by a semiquantitative scoring method. There was a 7.4% loss of activity after 24 hours of storing the unfixed material, increasing to 14.4% after three days, while storing the air-dried smears for up to four weeks did not change the ANAE activity. The mean cellular esterase activity was correlated to the clinical and cytologic findings. A stringent correlation could be found for patients smoking more than 30 cigarettes a day; they had a 17% increase in activity as compared to nonsmokers. In patients with bronchial asthma, the activity was 18% higher than the total mean. In three patients with pulmonary embolisms, the ANAE activity was also increased. Treatment with a combination of cytostatics and a corticoid caused a severe decrease. No correlation could be found to age, sex, inflammation or malignant or cardiac diseases. These findings indicate that the application of the ANAE reaction to routine cytologic specimens can contribute to the functional characterization of human alveolar macrophages. PMID- 3348058 TI - Expression of epithelial membrane antigen on malignant mesothelioma cells. An immunocytochemical and immunoelectron microscopic study. AB - The presence of epithelial membrane antigen (EMA) on malignant mesothelial cells found in pleural and ascitic fluids was demonstrated immunocytochemically using a monoclonal anti-EMA antibody. Serous fluids of 25 patients with malignant mesotheliomas were investigated. In 23 cases, varying numbers of EMA-positive tumor cells were present; in 2 cases, no such cells were found. Immunoelectron microscopy was performed both on Lowicryl-embedded sediments of serous fluids and by application of preembedding techniques using the immunogold method. Expression of EMA by the immunogold method was found selectively on the villi of the malignant mesothelioma cells whereas the nonvillous, flat surfaces were largely EMA-negative. The results indicate that immunoelectron microscopy may offer a useful adjunct in the diagnosis of malignant mesothelioma in serous fluids. PMID- 3348059 TI - The interval between the diagnosis of malignancy and the development of effusions, with reference to the role of cytologic diagnosis. AB - An analysis was made of the time lapse between the diagnosis of malignancy and the development of an effusion in relation to the sex and age of the patients and the site of the primary malignancy. The total number of patients studied was 254; of these, 171 patients had a pleural and 83 patients a peritoneal effusion. In the total group, sex distribution was two men to three women: about equal in the pleural effusion group and about two men to nine women in the ascites group, with the latter ratio reflecting the large number of primary malignant processes in the breast and ovaries. The average age at the time of the effusion, whether it was located in the pleural or in the peritoneal cavity, was about 55 years. This figure was roughly 60 years for men and 51 years for women. The nine-year average age difference between sexes can be explained by the size of the four largest groups of different primary malignant localizations and their sex distribution. The interval between the discovery of the primary malignancy and the first fluid sample was longer for patients with a pleural effusion (average of 77.0 weeks) than for patients with ascites (average of 54.5 weeks). The longest interval was seen in the breast carcinoma group, with the shortest interval in lung carcinoma patients. The interval was significantly longer for women, being 111.9 weeks for pleural effusions and 57.9 weeks for ascites (average for both sites of 88.7 weeks). In 30.7% of the patients, the primary malignancy was discovered at the same time or later than the effusion; in patients with lung cancer, a strikingly higher percentage of 53.0% was found. In this respect, the cytologic diagnosis of effusions is of great importance not only for the detection and proper identification of a malignant process but also as an indicator of the life expectancy of a patient. PMID- 3348060 TI - Necrosis of a Warthin's tumor following fine needle aspiration. AB - Fine needle aspiration (FNA) biopsy of a parotid mass demonstrated features diagnostic of a Warthin's tumor. Resection of the mass six weeks later yielded a necrotic nodule lacking distinguishing characteristics. This case illustrates infarction of the target lesion, a rare complication of FNA biopsy of salivary gland neoplasms. Correlation of the histology with the cytology will prevent diagnostic difficulties in such instances. PMID- 3348061 TI - Immunocytochemical analysis and cytomorphologic diagnosis on fine needle aspirates of lymphoproliferative disease. AB - Fine needle aspirates were used for the cytologic and immunologic analysis of 21 cases of lymphoproliferative disorders. Immunocytochemical studies performed on Cytospin preparations confirmed the cytomorphologic diagnosis in 19 cases. In one case, the morphology of both aspirates and surgically obtained material showed a reactive pattern while immunologic analyses were inconclusive on both types of material. Immunocytochemistry on tumor material obtained by fine needle aspirations was in agreement with immunohistochemistry on surgical biopsies in 15 of 16 patients with malignant lymphomas. We conclude that immunocytochemical studies performed on Cytospin material in conjunction with the cytologic diagnosis will lead to an increase in diagnostic accuracy as well as providing a means for subclassification of neoplastic lymphoid cells. Moreover, this technique appears to give results comparable to those obtained by histopathologic and immunohistochemical analysis on surgically removed lymph nodes. PMID- 3348062 TI - Pulmonary Hodgkin's disease. Diagnosis by fine needle aspiration. AB - The cytologic manifestations of pulmonary Hodgkin's disease in transthoracic fine needle aspirates from 13 patients with pulmonary radiologic abnormalities and a previous diagnosis of Hodgkin's disease are described. Classic Reed-Sternberg cells and lacunar cells were present in most cases. The so-called "mononuclear" Reed-Sternberg cells were identified in all cases. A cellular background consisting of variable numbers of histiocytes, eosinophilic and neutrophilic leukocytes and lymphocytes was frequently present. Such a background should stimulate a search for cells diagnostic of Hodgkin's disease. We conclude that the cytologic features of Hodgkin's disease are not only characteristic, but are also diagnostic, in patients with a prior history of Hodgkin's disease in whom pulmonary recurrence is suspected. PMID- 3348063 TI - Giant cell interstitial pneumonia in a hard-metal worker. Cytologic, histologic and analytical electron microscopic investigation. AB - A case of biopsy-proven giant cell interstitial pneumonia in a patient with occupational exposure to hard-metal dust is reported. Bronchial washings performed several days prior to open-lung biopsy yielded an almost exclusive population of nonpigmented alveolar macrophages and pleomorphic, phagocytic multinucleated giant cells. Microorganisms, viral inclusions in the giant cells, epithelioid histiocytes and well-formed granulomas were not seen. This cytologic picture strongly suggests the presence of giant cell interstitial pneumonia in a patient with restrictive lung disease, particularly when exposure to hard-metal dust is known or suspected. A specific diagnosis early in the course of the disease may facilitate removal of the individual from the workplace and forestall the development of end-stage interstitial fibrosis. Additionally, the working environment may be modified to minimize inhalational exposure. Recognition of this entity by the cytopathologist may direct diagnostic efforts toward accurate histologic evaluation and the identification of particulates by microprobe analysis of either cellular or biopsy material. PMID- 3348065 TI - False-positive diagnosis of adenocarcinoma in situ of the cervix. PMID- 3348064 TI - Squamous metaplasia of the prostate: a potential pitfall in fine needle aspiration cytology. PMID- 3348067 TI - The Q.A.-R.M. relationship. PMID- 3348066 TI - Strongyloides stercoralis hyperinfection in a patient with the acquired immune deficiency syndrome. PMID- 3348068 TI - Adjustment of adults to a visual impairment: preliminary findings. PMID- 3348069 TI - Survival of intensive care patients. II: Outcome prediction 1 hour after admission. AB - 978 patients from a multidisciplinary intensive care unit (ICU) were followed prospectively to evaluate outcome. At 1 year after admission the cumulative mortality was 26.5%. Age, medical history and different condition variables 1 h after admission were included in logistic regression models in order to identify risk factors for death in the ICU and afterwards. By combining these predictive factors, it was possible to describe clinically interesting patient groups with a low and a high risk, respectively, of dying. 330 patients younger than 65 years, without any history of cancer and without any condition risk factors 1 h after admission, had a cumulative mortality of 6% at 1 year as compared to another group of patients with a 1-year mortality of 63%. In a small group of patients who had all the identified risk factors, the mortality rate at 1 year was 100%. It was also possible to identify a low-risk group of 251 patients (26% of total) who had a risk of death in the ICU of less than 0.5% as compared to 9.6% for the average patient. PMID- 3348071 TI - When asleep, one is cooler on beta-blockade than on placebo. A study of pulmonary arterial blood temperature and skeletal muscle heat production in anaesthetized man. AB - The effect of beta 1-adrenergic blockade on body temperature was studied during general anaesthesia by means of a thermistor in an indwelling pulmonary arterial catheter. Metoprolol (200 mg daily) or placebo was given double-blind preoperatively for at least 2 weeks to 27 hypertensive patients undergoing abdominal surgery. A significantly greater temperature fall was observed in the metoprolol group compared with the placebo group. Heat production in the rectus abdominis muscle, measured by direct microcalorimetry, was significantly lower after metoprolol. The hypothermic effect of beta-adrenergic blockade during anaesthesia deserves special attention. PMID- 3348070 TI - The effect of isoflurane on cerebrospinal fluid pressure in patients undergoing neurosurgery. AB - Ten patients with intracerebral tumours (TC) and 13 patients with subarachnoid haemorrhage (SAH) from a ruptured cerebral arterial aneurysm were studied before intracranial surgery, and during a 3-h postoperative period. Cerebrospinal fluid pressure (CSFP) determined by an intraventricular (TC group) or intraspinal (SAH group) catheter, and mean arterial blood pressure (MABP) were recorded under neurolept anaesthesia (control) followed by isoflurane inhalation. These two measurements were performed during normocapnia. A third measurement was made during hypocapnia, with unchanged isoflurane concentration. After the experimental period, isoflurane remained the main anaesthetic agent throughout the surgical procedure. After recovery from anaesthesia, the patients were monitored with CSFP and blood pressure during the first postoperative hours, and the quality of breathing was assessed by hourly blood-gas analyses. The results show that isoflurane causes a 10-14% reduction of MABP with no further changes during hyperventilation. Mean CSFP increased 27% in the TC group, and 12% in the SAH group after isoflurane induction and decreased from these levels by 29% during hyperventilation in both groups. Consequently, the impact on cerebral perfusion pressure (CPP) by isoflurane was a 19% and 21% mean decrease in the TC and SAH group, respectively. Controlled hyperventilation reduced this effect by partially restoring control CPP values, with 8% and 14% increase, respectively. In the postoperative follow-up, all patients had normal breathing and blood pressure with low values of CSFP. It is concluded that isoflurane can be used in intracranial surgery with adequate safety if combined with controlled hyperventilation. PMID- 3348072 TI - Age, fiber type composition and in vitro contracture responses in human malignant hyperthermia. AB - Muscle fiber typing and in vitro contracture tests were performed in 59 patients investigated for susceptibility to malignant hyperthermia (MH). Eighteen patients were found to be susceptible to MH. There was no difference in age or fiber type distribution between MH susceptible and non-susceptible patients. No correlation was found between age and fiber type distribution. Separate analyses for each diagnostic group revealed no relationship between age or fiber type distribution and response to halothane or caffeine. When all caffeine results were pooled, however, there was a significant effect of age on the caffeine specific concentration (the concentration eliciting a contracture of 1 g), but not on the caffeine threshold concentration (the minimal concentration eliciting an increase in tension). It is concluded that age and fiber type distribution have no influence on MH diagnosis, if the protocol of the European MH Group for evaluation of susceptibility to MH is followed. PMID- 3348073 TI - Premedication with intramuscular dixyrazine: (Esucos). A controlled double-blind comparison with morphine-scopolamine and placebo. AB - Ninety patients scheduled for general or orthopaedic surgical procedures were randomly assigned to receive one of three i.m. premedications: dixyrazine 0.5 mg kg-1; morphine 0.15 mg kg-1 and scopolamine 0.0065 mg kg-1; or placebo. The premedication was administered and evaluated in a double-blind fashion. The patients were anaesthetized with thiopentone, fentanyl, pancuronium, and ventilated with nitrous oxide in oxygen. The three premedications had no noticeable anxiolytic effect. Although there was no difference in the frequency of observed postoperative nausea and vomiting between the three groups, premedication with dixyrazine nonetheless reduced the patients' experience of postoperative nausea as well as their need for postoperative antiemetics. Although patients in the two treatment groups were significantly more sedated immediately before induction of anaesthesia than patients receiving placebo, the degree of postoperative sedation was similar in all three groups. Morphine scopolamine caused more postoperative dizziness than dixyrazine and placebo. Lack of recall was produced by both morphine-scopolamine and dixyrazine. It is concluded that premedication with dixyrazine is a useful alternative, especially in patients who have previously experienced postoperative nausea and vomiting. PMID- 3348074 TI - Venous blood concentration of lidocaine after nasopharyngeal application of 2% lidocaine gel. AB - In 34 subjects undergoing topical anaesthesia with lidocaine gel (2% xylocaine gel), the concentrations of lidocaine base were measured in repeated venous blood samples. Twenty-three patients (Group I) were given 20 ml of 2% lidocaine gel (400 mg of lidocaine) and six subjects (Group II) 40 ml of 2% lidocaine gel (800 mg of lidocaine) nasopharyngeally, the gel reaching the pharynx being swallowed. Five minutes after administration of the gel, a gastric tube was introduced via the nasal cavity. In six patients (Group III), the bladder was catheterised in addition to insertion of a gastric tube. Before the catheter was introduced, these patients were given lidocaine gel nasopharyngeally (400 mg) and endourethrally (400 mg). After the introduction of the gastric tube, all subjects (except four volunteers in Group II) were given general anaesthesia. Before intubation, the patients in Group III also received lidocaine spray laryngotracheally (50 mg; 10% xylocaine spray). The initial absorption of lidocaine was rapid, although the blood concentrations were low. The mean peak concentrations (Cmax) of lidocaine in the three groups were 0.57, 1.39 and 0.73 micrograms/ml, respectively. The blood concentration in Group II was significantly higher than those in Groups I and III. The mean length of time between the nasopharyngeal application of lidocaine gel and the time when Cmax was reached (tpeak) was the same in all three groups (60-70 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348075 TI - Pulmonary artery pressure: flow relationships in hyperoxic and in hypoxic dogs. Effects of methylprednisolone. AB - Methylprednisolone has been reported to impair hypoxic pulmonary vasoconstriction in isolated lungs, possibly by inhibiting the generation of vasoconstricting products of arachidonic acid metabolism. We investigated the effects of methylprednisolone on mean pulmonary artery pressure (PAP):cardiac index (Q) relationships in intact pentobarbital anaesthetized dogs ventilated alternatively in hyperoxia (fraction of inspired O2, FiO2 0.4) and in hypoxia (FiO2 0.1). Cardiac output was increased by opening an arterio-venous femoral fistula or reduced by stepwise inflations of a balloon in the inferior vena cava. Five point PAP:Q relationships were found to be rectilinear in all experimental conditions. Over the entire range of Q studied (2 to 5 l/min.m2), hypoxia increased PAP in seven dogs ("responders") and did not affect PAP in three other dogs ("non responders"). A hypoxic pulmonary pressor response was restored in these three "non-responders" by administration of 1 g acetylsalicylic acid iv. Methylprednisolone 30 mg/kg iv had no effect on hyperoxic and on hypoxic pulmonary vascular tone in the "responders" and in the "non-responders" treated with acetylsalicylic acid. An additional dog pretreated with methylprednisolone 30 mg/kg iv 24 h before the experiment still had a marked hypoxia-induced increase in PAP over the entire range of Q studied. Thus a large dose of methylprednisolone does not affect hypoxic or hyperoxic pulmonary vascular tone in intact dogs. These data do not support the hypothesis that products of arachidonic acid metabolism mediate hypoxic pulmonary vasoconstriction. PMID- 3348076 TI - Superoxide dismutase and catalase failed to improve neurologic outcome after complete cerebral ischemia in the dog. AB - Superoxide dismutase (SOD) and catalase, natural scavengers of free oxygen radicals, or saline were administered as a continuous systemic infusion to 12 dogs, in a blind randomized fashion, starting 10 min prior to a 10-min episode of complete cerebral ischemia, and continued thereafter for 60 min. Reversible complete cerebral ischemia was achieved by simultaneously occluding the ascending aorta and venae cavae. There were no significant differences in physiological variables (arterial blood gases, hemoglobin, mean arterial blood pressure, heart rate, and temperature) between the two groups, either pre-ischemia or post ischemia. There was no significant difference in neurologic outcome when evaluated at 48 h post-ischemia. It has previously been reported that the same dose of SOD and catalase as used in the current study could reduce infarct size by 50% when given systemically before reperfusion following coronary ischemia in dogs. The lack of a measurable effect on neurologic outcome in our cerebral ischemic model might be because of the failure of the free oxygen radical scavengers to reach the ischemic cells in sufficient amounts, or because free oxygen radicals do not contribute to brain injury following complete cerebral ischemia. PMID- 3348077 TI - The double J-spring guide wire and its hazards. Partially retained double J-wire: a complication during central venous catheterization. Case report. AB - A case is presented in which the outer part of a double J-spring guide wire was retained in the patient because of separation of the two parts. Warning against the use of this kind of wire is given. PMID- 3348078 TI - Baroreceptor control of central and regional hemodynamics with isoflurane in the dog. AB - Central and regional hemodynamics were studied at five levels of carotid sinus baroreceptor stimulation and three isoflurane levels. Apart from iliac blood flow, all regional blood flows, together with mean aortic pressure, power and flow decreased in response to an increasing anesthetic level and/or carotid sinus baroreceptor stimulation. These effects were additive with no significant interaction between the two experimental factors. At the carotid sinus reflex set point pressure, isoflurane attenuated the ability of carotid sinus baroreceptors to change mean aortic pressure and power together with the maximum capacity of the carotid sinus baroreceptors to produce vasoconstriction. The maximum capacity of the carotid sinus baroreceptors to produce vasodilation was unaffected by isoflurane. Vagotomy only modified hemodynamic set point values at low isoflurane levels, increasing regional resistances at the expense of flow except for the iliac bed. Following vagotomy, reflex gain was increased as was the maximum capacity of the cardiovascular system to vasoconstrict and vasodilate in response to carotid sinus pressure stimulation, together with the range of arterial pressure control. PMID- 3348079 TI - Survival of intensive care patients. I: Prognostic factors from the patient's medical history. AB - All adult patients (978) admitted in 1983 to a multidisciplinary intensive care unit (ICU) were studied prospectively. 9.6% died in the unit. The cumulative mortality was 26.5% 1 year after admission. Of the patients who were 65 years and older, 43.1% had died after 1 year compared to 10.6% in the youngest age group (15-44 years). Using multiple logistic regression analyses, prognostic factors for mortality were identified. All the factors were known at the time of admission. Risk factors for death in the ICU included age, admission for disorders in several organ systems, cardiopulmonary arrest and acute respiratory disorder. In addition to age and acute conditions at the time of admission, cumulative mortality after 1 year was also influenced by chronic conditions such as diabetes mellitus, chronic heart failure and cancer. These data document the importance of taking age and chronic illness into account when making a prognosis for intensive care patients. PMID- 3348080 TI - Amyloid deposition in the nucleus basalis of Meynert complex: a topographic marker for degenerating cell clusters in Alzheimer's disease. AB - The deficiency of the cholinergic cortical projection system arising in the different basal forebrain structures collectively referred to as nucleus basalis of Meynert complex is a constant finding in Alzheimer's disease, a disorder which is neuro-pathologically characterised by the appearance of three intracerebral formes of twisted beta-pleated sheet (amyloid) fibrils, neurofibrillary tangles, amyloid-containing neuritic plaques and congophilic amyloid angiopathy. In the present study the quantitative relationship between these hallmarks of the disease, amyloid deposition and neuronal loss in the cholinergic basal forebrain system, was investigated in ten cases of Alzheimer's disease. Besides a constant involvement of the cerebral cortex and hippocampus, all cases of Alzheimer's disease show a large amount of amyloid in the medial septal nucleus, in the diagonal band nucleus and in the substantia innominata which is correlated with neuronal loss in these areas. These amyloid deposits in the basal forebrain are due to congophilic angiopathy associated with plaques and neurofibrillary tangles. The distribution of amyloid deposition in the basal forebrain is restricted entirely to those neuronal clusters which represent the origin of cholinergic innervation of the cerebral cortex and hippocampus. Immediately adjacent structures are not affected. These findings suggest a pathogenetic role of amyloid deposition in the mechanism of degeneration of the cholinergic basal forebrain system. PMID- 3348081 TI - The association of infantile osteopetrosis and neuronal storage disease in two brothers. AB - Neurological manifestations in infantile osteopetrosis are common and varied, and not always attributable to the skeletal pathology. An unusual association of osteopetrosis with neuronal storage of ceroid lipofuscin is reported in two infant brothers born of nonconsanguinous parents. The first child became symptomatic at age 5 days with weight loss and vomiting. He had poor head control, hypertonia, and persistent fisting, and died at age 2 months. In the second infant, the diagnosis of osteopetrosis was confirmed at age 2 days. His neurological symptoms included blindness, deafness, and recurrent seizures. The infant died at 7 months of age. In both cases, autopsy confirmed the diffuse bony sclerosis with hepatosplenomegaly and extramedullary hematopoiesis. Neuropathological examination revealed cerebral atrophy with ventricular dilation, neuronal loss, and astrogliosis. The most striking finding was widespread accumulation of neuronal ceroid lipofuscin associated with formation of axonal spheroids. The optic nerves were compressed at the optic foramina and showed loss of myelinated axons and gliosis. Rapid Golgi impregnations of neurons from the calcarine cortex in the second infant were analyzed quantitatively, showing a reduction in the total dendritic length and number of branches. The primary defect in osteopetrosis is thought to be a lysosomal dysfunction involving the monocyte cell line from which osteoclasts are derived. Thus, the association in two brothers of osteopetrosis with accumulation of neuronal ceroid lipofuscin may not be fortuitous. The neuronal storage disorder in this instance probably reflects lysosomal dysfunction. PMID- 3348083 TI - A study of cerebellar and cerebral cortical degeneration in miniature poodle pups with emphasis on the ultrastructure of Purkinje cell changes. AB - In a litter of three Miniature Poodles, a normal female pup contrasted with two males which displayed severe equilibrium and postural disturbances soon after birth. In the male pups diffuse cerebral cortical degeneration accompanied cerebellar cortical atrophy, which was characterized by extensive loss and degeneration of Purkinje neurons. As in some prior histological descriptions of canine cerebellar atrophies, degenerating Purkinje cells appeared either pale, swollen and vacuolated or shrunken and hyperchromatic. Swollen vacuolated cell bodies and condensed necrotic neurons were scattered through the cerebral cortex. Ultrastructural studies revealed that the vacuolar degeneration in Purkinje and cerebral neurons was referable to marked dilation of endoplasmic reticulum and loss of ribosomes. In shrunken Purkinje neurons, increased cytoplasmic eosinophilia was associated with a decline in Nissl bodies and accumulations of mitochondria and especially lamellar bodies. The latter, stacked derivatives of endoplasmic reticulum, were not encountered in shrunken cerebral perikarya. Lamellar bodies reached giant proportions in the dendritic stems of degenerating Purkinje neurons. In Purkinje axons, however, these bodies often were overshadowed by aggregates of axoplasmic tubules. The cytological changes in these Poodle pups were notably different from those reported in earlier ultrastructural studies of canine inherited cerebellar degenerations. PMID- 3348082 TI - Cerebral microangiopathy in stroke-prone spontaneously hypertensive rats. An immunohistochemical and ultrastructural study. AB - The morphology of cerebral microvessels was studied immunohistochemically and ultrastructurally in 6- to 9-month-old normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) with a systolic blood pressure of 138 +/- 15 mm Hg, 189 +/- 9 mm Hg, and 258 +/- 30 mm Hg respectively. Regions with major opening of the blood-brain barrier (BBB) were revealed by an i.v. injection of Evans Blue. Multifocal BBB opening with massive leakage of plasma constituents rich in fibrinogen-fibrin-related antigen occurred in SHRSP with a blood pressure above 210-220 mm Hg. BBB-leakage sites were found in the cerebral cortex and the basal ganglia, most frequently in the arterial border zones. The perivascular tissue spaces were dilated within the BBB-leakage sites, in particular around arterioles. Damaged endothelial and smooth muscle cells were replaced by fibrin-like material, multiple layers of basement membranes and bundles of collagen fibrils surrounded by proliferated fibroblasts. The degenerative-infiltrative-proliferative disease process transformed short segments of single arterioles into severely thickened, tortuous and stenotic vessels. Fibrinoid degeneration, formation of microaneurysms and fibrin-rich vascular occlusions were observed. In contrast, only minor or no vascular alterations were seen in regions with preserved BBB in SHRSP and SHR. A severely increased intraluminal pressure load appears to be of major pathogenetic importance for breakdown of the BBB and initiation of the vascular disease process in SHRSP. However, since only short segments of a limited number of widely separated vessels are severely affected, and the number of affected vessels increase towards arterial end and border zones, additional predisposing and aggravating factors may play significant roles in the development of fibrinoid vascular lesions in arterial hypertension. PMID- 3348085 TI - Microvascular disturbances and edema formation after repetitive ischemia of gerbil brain. AB - Three transient episodes of 5 min ischemia spaced at 1-h intervals were produced in Mongolian gerbils by bilateral carotid artery occlusion with an implanted vascular occlusion device. The interval of 1 h was chosen to allow for the development of post-ischemic hypoperfusion between the ischemic episodes. Three minutes and 1 h after each ischemic episode, and 6 and 24 h after the third occlusion, Evan's blue (EB) was injected intravenously to trace circulating blood, and the number of perfused capillaries was determined in various brain regions by fluorescence microscopy. Brain edema was evaluated by measuring specific gravity in tissue samples taken from adjacent areas. Repetitive ischemia caused progressively increasing brain edema and a progressive reduction of the number of perfused capillaries. Immediately after each ischemic episode, transient recruitment of capillaries occurred, thus excluding no-reflow as a main pathogenetic factor of microcirculatory disturbances. The pattern of microcirculation 6 and 24 h after the last occlusion revealed a redistribution of circulating blood, characterized by a reduction in the number of EB-filled capillaries associated with a noticeable dilatation of the larger vascular channels. Our studies suggest a close interrelationship between post-ischemic microcirculatory hypoperfusion and the development of brain edema, the degree and extent of which progresses with the repetition of ischemic episodes when they are carried out during the periods of hypoperfusion. PMID- 3348084 TI - Ultrastructural studies of glycoconjugates in brain micro-blood vessels and amyloid plaques of scrapie-infected mice. AB - Lectin or glycoprotein-gold complexes and samples of scrapie-infected mouse brain embedded in Lowicryl K4M were used for ultrastructural localization of glycoconjugates. The lectins tested recognize the following residues: beta-D galactosyl [RCA, Ricinus communis agglutinin (aggl.) 120], N-acetyl and N glycolyl neuraminic acid (LFA, Limax flavus aggl.), N-acetyl-D-glucosaminyl and sialyl (WGA, Wheat germ aggl.), N-acetyl-D-galactosaminyl (HPA, Helix pomatia aggl., and DBA, Dolichos biflorus aggl.), alpha-D-mannosyl/alpha-D-glucosyl (Con A, Concanavalin A), alpha-D-galactosyl and alpha-D-galactopyranoside (BSA, Bandeirea simplicifolia aggl., izolectin B4). Labeling of the majority of micro blood vessels (MBVs) located outside the plaque area and in the remaining cerebral cortex was similar to that which has been previously observed in non infected animals. Some MBVs, however, located inside the plaque area and surrounded directly by amyloid fibers showed attenuation of the endothelium, the surface of which was scarcely and irregularly decorated with RCA, LFA, WGA and Con A. These abnormalities in the composition of glycoconjugates can be associated with previously noted increased permeability of some MBVs in the brains of scrapie-infected mice. Some vessels in the plaque area were encapsulated by perivascular deposits of homogeneous or flocculogranular material containing several glycoconjugates. A very intimate structural relation between reactive (microglial-like) cells and amyloid fibers suggests the participation of these cells in elaboration of plaque material. Labeling of the cell surface and adjacent amyloid fibers with the same lectins (RCA, WGA, DBA, Con A) suggests the possibility that the glycosylation of these fibers occurs extracellularly. Only WGA and DBA were occasionally labeling some Golgi elements of the reactive cells. PMID- 3348087 TI - Correlative study of the incidence of opaque, necrotic and regenerative fibers in Duchenne dystrophy. AB - We studied the incidence of opaque, necrotic, and regenerative muscle fibers (OFs, NFs, RFs) in muscle biopsies from 21 patients, aged 8 months to 24 years, with Duchenne muscular dystrophy (DMD). OFs varied from case to case with an average rate of 8.3%. NFs and RFs were high in younger patients and decreased with age. The incidence of OFs, NFs, and RFs correlated to patient age with these coefficients: r = -0.38, -0.91, and -0.86. Except for OFs, all correlations were significant (p less than 0.001). There was no significant correlation between the incidence of OFs and NFs in each case of DMD. Considering the results of previous biochemical analysis of single OFs, we suggest that OFs may comprise two types of muscle fibers: (1) pathological muscle fibers to be regarded as precursors of NFs, and (2) muscle fibers undergoing artificial changes. PMID- 3348088 TI - Traumatic fascicular neuroma. AB - A 72-year-old man had developed amiodarone neuropathy. He was found, at biopsy, to have a fascicular neuroma of his right sural nerve, unassociated with his underlying neuropathy, apparently due to blunt trauma, as electroneurographic needling of this nerve could safely be ruled out by the patient and his physicians. Such fascicular neuromas, which may remain without sensory deficits, may develop at an unknown frequency, and may only be uncovered by biopsy--or autopsy--in a coincidental neuropathic process. PMID- 3348086 TI - Ultrastructural features of a brain injury model in cat. I. Vascular and neuroglial changes and the prevention of astroglial swelling by a fluorenyl (aryloxy) alkanoic acid derivative (L-644,711). AB - We present qualitative and quantitative ultrastructural observations on the changes induced in neuroglia and blood vessels of gray matter of cat brain by an experimental acceleration-deceleration injury which, when used alone, causes negligible morbidity and mortality, but, when combined with systemic hypoxia, leads to coma and delayed death in approximately 50% of experimental subjects. An increase in the proportion of neuropil occupied by astrocytic cytoplasm is detectable qualitatively in layer Vb of pericruciate cortex 20 min after injury without hypoxia, and is maximal (22%, as measured morphometrically, vs 11.4% in controls) 40 min afterward. Near-normal values (14.1%) are obtained 100 min following the insult. If trauma is succeeded 40 min later by a 60-min period of hypoxia, there is prolongation of astrocytic edema and other neuroglial accompaniments of the traumatic lesion, such as aggregation of nuclear nucleoprotein granules and, in astrocytes, fusion of rosette ribosomes and enlargement of mitochondria. A decrease in luminal area occurs in capillaries 40 min after trauma applied alone. Hypoxia without trauma leads to a significant increase in capillary luminal area, which, however, is abolished when trauma precedes the hypoxic interlude. Intravenous injection of a non-diuretic, fluorenyl derivative (L-644,711) of (aryloxy)alkanoic acid loop diuretics, completely prevents the astrocytic swelling ordinarily present 40 min after acceleration-deceleration injury. Also, L-644,711 improves mortality and morbidity scores in cats subjected to trauma with hypoxia. We suggest that astroglial swelling may be a critical step in the evolving pathology of this head injury model and its prevention, as by L-644,711 administration, may have relevance to the treatment of cerebral edema in human head injury and other clinical disorders accompanied by astrocytic swelling. PMID- 3348089 TI - Modifications and problems of behavioural inpatient management of anorexia nervosa: a "patient-suited" approach? AB - Several treatment modalities, especially behaviour therapy, had been successfully administered in order to normalize body weight in anorexia nervosa inpatients. However, improvement in affective, cognitive and psychosocial features and associated psychopathologic symptoms was rather poor. It is hypothesized that the limited effect of behaviour therapy may be also due to therapeutic shortcomings of the behavioural treatment programme. In the present study of 16 anorectic inpatients a behavioural treatment programme, which had been applied in a former investigation at the same unit, was modified and yielded the following results: rapid increase in weight, good improvement of anorectic and depressive symptoms and a treatment duration of less than 3 months. Although the short-term outcome of the modified treatment programme is encouraging, the therapeutic difficulties encountered in this programme deserve special attention and its long-term effects on the course and prognosis of anorexia nervosa have to be established. PMID- 3348090 TI - Priapism and neuroleptics: a case report. AB - We present a case of priapism caused by the alpha adrenoreceptor blocking action of a butyrophenone. The problem was solved surgically performing a cavernousspongiosum fistula. PMID- 3348091 TI - Social factors associated with the use of psychotropic drugs: alcohol abuse and minor psychiatric morbidity in the community. AB - The association of socio-demographic factors and life events with psychotropic drug consumption, alcohol abuse and minor psychiatric morbidity was investigated in a representative community sample of 181 respondents. The statistical model used was a logistic multiple regression analysis. Psychotropic drug use was best predicted by family size and employment status; alcohol abuse by sex, family size and "exit" events; and minor psychiatric morbidity by sex, marital status and undesirable life events. PMID- 3348092 TI - Eleven year follow-up of 300 young opioid addicts. AB - A cohort of 300 young opioid addicts (203 male and 97 female) attending the City of Copenhagen Drug Treatment Service (200) or the Nordvang Hospital (100) for first-time treatment during 1973 was personally followed up in 1980 and 1984. In both studies about 90% were traced. Outcome was classified on a four-step scale according to current drug status and occupational status. In 1984 24% of the cohort were classified in the best outcome class while 26% were dead, yielding an average mortality of 2.4% per year. Sixteen per cent were classified as substance users, including persons mostly abusing alcohol or tranquilizers. In contrast to our predictions in 1980 the number of persons achieving stable abstinence does not turn out to be steadily increasing with time. The number of active drug addicts declines mainly because they die, not because they achieve abstinence. According to more strict criteria less than 20% would be classified as truly recovered. Another 5 - 10% achieve some unstable abstinence. The long-term prognosis seems to be highly unfavourable for the study population as a whole. PMID- 3348093 TI - Self rated depression in relation to DSM-III classification: a statistical isolinear multiple components analysis. AB - The Zung Self-Rating Depression Scale (SDS) was presented to 99 depressed inpatients. The patients were categorized according to DSM-III as suffering from minor depression, major depression without melancholia and major depression with melancholia and/or with psychotic features. Differences in self-reported symptoms between these categories were studied with multivariate statistical techniques including linear discriminant analysis (LDA) and statistical isolinear multiple components analysis (SIMCA). Patients with minor depression rate themselves significantly less depressed than those with major depression. Patients with major depression without melancholia are less depressed than those with melancholia and/or psychotic features. The three DSM-III depressive categories can be regarded as belonging to a clinical continuum in which they form relevant levels with quantitative differences in self-reported symptoms. These differences are not only defined by gradual shiftings in the overall severity of illness, but also by quantitative differences in the severity of some target symptoms, i.e. agitation, retardation, diurnal variation, loss of libido, fatiguability, insomnia, anorexia, sadness and anhedonia. PMID- 3348094 TI - Mental health in the population approaching retirement age in relation to physical health, functional ability and creativity. Findings of the TURVA project. AB - This is the second paper dealing with a Finnish long-term prospective study, the objective of which is to shed light on adjustment to retirement and old age. At this point, only the results of the initial survey carried out in 1982 are available. The material consisted of a random sample of 200 individuals born in 1920 and living in Turku, and a corresponding sample of 189 persons living in rural areas in the neighborhood of Turku. The method consisted of a structured interview, certain questionnaires and a physical examination. There was a considerable discrepancy between the subjects' subjective working disability and the frequency of evident and handicapping physical illnesses found by the physician. This difference was largely explained in terms of mental problems. Dissatisfaction with life was clearly more common in subjects receiving a disability pension and in those classified as psychiatric cases than in others. PMID- 3348095 TI - Cognitive impairment among the elderly in a Korean rural community. AB - Cognitive function among the elderly aged 65 or older was studied in a rural community of Korea. The prevalence rates of cognitive impairment were significantly higher in females (64%) than in males (33%). Sex differences of prevalence of both mild impairment (25% in males vs 45% in females) and severe (8% in males vs 19% in females) reached statistically significant levels. The prevalence of severe impairment increased with age, and the age-related increase was steeper after 80 in males and after 75 in females. The prevalence of mild impairment, on the other hand, did not increase so prominently with aging. From this point of view, it could be assumed that severe cognitive impairment may be highly related to real dementia, and that the elderly with mild impairment may consist of heterogenous groups associated with cognitive dysfunction of mild degree. PMID- 3348096 TI - Somatization, depression and medical illness in psychiatric inpatients. AB - In a study to determine the relationship between somatic symptoms and psychiatric diagnosis, 206 consecutively admitted inpatients at the University of Iowa Psychiatric hospital were given a structured medical history (MH) and physical examination (PE). Depressed patients were significantly older, had an increase in number of medical diagnoses (NDX), and were found to have a significant increase in somatic symptoms in which there was no confirmatory evidence on the PE and in which there was confirmation on the PE. When age, sex, and NDX were controlled for, depressed patients did not have an increase in either of the types of somatic symptoms noted above but did have a slight increase in the vague somatic symptoms in which PE findings would be unlikely. Our results suggest that the majority of the increases in somatic symptoms in depressed patients may not be due to depressive psychopathology but rather to their increased number of medical problems and increased age. PMID- 3348097 TI - Self-poisoning among four immigrant groups. AB - Rates of deliberate self-poisoning in four immigrant groups, Asian, West Indian, Irish and Scottish were compared with those of English-born residents in an inner city area of Birmingham. For both Asian and West Indian groups males and older females were underrepresented but young females had rates similar to the English group. Irish females and Scottish of both sexes were overrepresented. The rates of self-poisoning for all four immigrant groups considerably exceeded those of their country of origin, the difference being most marked among young Asian females. Explanations for these findings are examined. PMID- 3348099 TI - The holistic approach and mechanical fault finding in clinical diagnosis--a false antagonism. PMID- 3348100 TI - Risk factors for sudden and non-sudden coronary death. AB - The impact of risk factors for sudden and non-sudden coronary death was investigated in 3,589 Finnish men aged 40-59 years at entry from a prospective population survey. During a mean follow-up time of 11 years, 234 coronary deaths occurred, 150 of which were sudden, i.e. ensuing within 1 hour of the onset of symptoms. The severity of the manifestations of CHD at baseline investigation appeared to be a powerful predictor of sudden coronary death. Smoking and high serum cholesterol were significant predictors of sudden coronary death. High serum cholesterol was an equally significant predictor of sudden and non-sudden coronary death. High blood pressure did not appear to significantly increase sudden coronary death but increased the incidence of non-sudden death significantly. Obesity and diabetes did not appear to be independent risk factors for sudden coronary death. Smoking and high serum cholesterol were significant risk factors for sudden coronary death in men with manifestations of coronary heart disease. The results suggest that reduction of primary risk factors, especially smoking and high serum cholesterol, is important even after coronary heart disease has become manifest. PMID- 3348098 TI - A comparative study on schizophrenia diagnosed by ICD-9 and DSM-III: course, family history and stability of diagnosis. AB - Data from the Taipei Center of the International Pilot Study of Schizophrenia were reanalyzed using the ICD-9 and DSM-III diagnoses at 7-year follow-up. Patients diagnosed as schizophrenic according to DSM-III were shown to be a more homogeneous group in terms of their clinical manifestations, social functions and family psychiatric history than those defined as schizophrenic by ICD-9. The discordant cases of ICD-9 schizophrenia and DSM-III affective disorders were found to be different from the concordant schizophrenic group, but similar to the concordant group of affective disorders diagnosed by ICD-9 and DSM-III. Thirty five per cent of mood-incongruent psychotic major depressive disorders defined by DSM-III at initial evaluation were diagnosed as schizophrenia at 7-year follow up. PMID- 3348101 TI - Pulmonary-artery cineangiocardiography and echocardiography for detection of cardiac sources of cerebral embolism. AB - Sixty-two patients with ischemic stroke possibly due to embolism of cardiac origin were investigated by pulmonary artery-cineangiography (PACAC) and echocardiography (UCG) to detect intracardiac thrombi. The proportion of intracardiac thrombi found by PACAC was 31% and by UCG 15%. The presence or absence of atrial fibrillation correlated well with PACAC findings of an intraventricular clot but poorly with UCG. Similarly, there was a significant association between ischemic heart disease and intraventricular thrombi detected by PACAC investigations but not with the results obtained by UCG. PACAC seems superior to UCG in the detection of intracardiac thrombi after possible embolic stroke. PMID- 3348102 TI - Serum apolipoproteins, lipoproteins and fatty acids in relation to ischaemic heart disease in northern and southern European males. AB - Serum apolipoprotein and lipoprotein concentrations, fatty acid spectra of various lipids, dietary habits and common risk factors for ischaemic heart disease were studied in 73 and 77 randomly selected, 50-year-old healthy men in Naples and Stockholm, respectively. Mean serum cholesterol concentration was higher in Stockholm than in Naples men (6.23 vs. 5.47 mmol/l, p less than 0.001) as were low (LDL) (4.08 vs. 3.57 mmol/l, p less than 0.001) and high (HDL) (1.40 vs. 1.25 mmol/l, p less than 0.001) density lipoprotein fractions. Mean serum triglyceride concentrations did not differ. Mean apolipoprotein B and C-I concentrations were higher in Stockholm men (1,116 vs. 1,020 mg/l, p less than 0.05 and 96 vs. 79 mg/l, p less than 0.01, respectively). Stockholm men derived significantly more of their calories from fat (38 vs. 28%, p less than 0.001) and the dietary fat had significantly lower polyunsaturated-to-saturated fatty acid ratio (P/S-ratio 0.29 vs. 0.51, p less than 0.001), and less from carbohydrate (44 vs. 49%, p less than 0.001) than Naples men, respectively. Mean caloric intake and mean weight/height index did not differ. Stockholm men had higher blood pressures, but there were more smokers among Naples men. The higher fat intake in Stockholm men may offer an explanation of the differences seen in lipoprotein and apoprotein concentrations and compositions but other factors, such as genetic influences cannot be excluded. A greater cholesterol flux through the plasma compartment in Stockholm men may be one important factor contributing to the higher incidence of ischaemic heart disease in this population. PMID- 3348103 TI - Chronic atrial fibrillation. Long-term results of direct current conversion. AB - One hundred consecutive patients admitted in 1980-82 for direct current conversion of chronic atrial fibrillation (AF) were followed. The first attempt to convert was made without the institution of class I antiarrhythmics. If AF relapsed, patients were selected for further conversions, in connection with which quinidine or disopyramide treatment was instituted. The proportion of patients maintaining sinus rhythm (SR) one and two years after the first conversion was 23% and 16%, after the second conversion 40% and 33% and after any number of conversions [1-12] 54% and 41%. Fifty-three per cent of the patients were symptomless before at least one conversion. Of the patients maintaining SR two years after conversion, 46% did not receive antiarrhythmic therapy. More than two conversions should be exceptional since symptoms of AF are often absent and the additional effect of further conversions is minor. A first attempt to convert without antiarrhythmics identifies a substantial proportion of patients maintaining SR without any prophylactic antiarrhythmic therapy. PMID- 3348104 TI - Exercise test in patients with sarcoidosis. The importance of repolarization disturbances. AB - The study population comprises 28 patients with sarcoidosis who all had repolarization disturbances in their exercise ECGs. None of the patients had hypertension or known cardiovascular disease, and all but two were non-smokers. The mean age was 45 years. Exercise test with beta-adrenergic blockade was performed within one month of the first examination. Persisting abnormal ST-T changes in exercise ECGs after beta-blockade were seen in 12 (43%) patients. No significant relationship was found between persisting ST-T changes and age, sex, chest X-ray stage, lung function or working capacity. In an earlier study, we found ST-T abnormalities in exercise ECG in 56 of 127 individuals (44%) in a consecutive 5-year study of patients with newly detected sarcoidosis. From this and the present report we postulate that, in our region, as much as 20% of the patients with newly detected sarcoidosis might have organic myocardial disease, possibly of sarcoid origin, as shown by repolarization disturbances in exercise ECG. If ECG abnormalities in the ST-T region are present in patients with sarcoidosis, exercise ECG with beta-blockade is a simple way of establishing suspicion of organic myocardial lesions. If exercise ECG abnormalities in the ST T region persist after beta-blockade, careful clinical follow-up is recommended, and, in some patients early steroid therapy should be considered. PMID- 3348105 TI - Positive Coombs' test associated with ulcerative colitis. A prevalence study. AB - Among 112 patients with ulcerative colitis (UC), a positive Coombs' test was detected in two cases. The immunoglobulins were IgG and no complement could be detected on the red cells. None of the two patients showed laboratory evidence of hemolysis, although reduced red cell survival was suspected in one patient with a 6-year history of UC, previous autoimmune hemolytic anemia and a positive in vitro monocyte-macrophage phagocytosis test. The HLA-antigens in the two patients were different except for the common antigen HLA-A1. PMID- 3348106 TI - Rhabdomyolysis and acute renal failure following an overdose of doxepine and nitrazepam. AB - A 50-year-old woman developed rhabdomyolysis and myoglobinuric renal impairment after an oral dose of 250 mg nitrazepam and 1,250 mg doxepin. Serum creatinine increased from 70 mumol/l to 472 mumol/l in two days. Serum creatine phosphokinase reached a maximal level of 391 mu kat/l (reference range less than 2.5 mu kat/l) on the third day and serum myoglobin was maximally 910 nmol/l (reference range less than 4.5 nmol/l) on the fourth day after the overdose. Passive and active movements of the knees and ankles became increasingly restricted, but the patient felt no muscle pain. Diuresis decreased to 20-22 ml/hour in spite of repetitive doses of furosemide, but was enforced to greater than 100 ml/hour by vigorous infusion of saline. Haemodialysis was avoided on this regimen. It is suggested that in patients intoxicated with nitrazepam and/or doxepin, rhabdomyolysis should be suspected when a rapidly increasing serum concentration of creatinine is found, even in the absence of muscle pain. PMID- 3348107 TI - Cyclic neutropenia terminating in permanent agranulocytosis. AB - A patient with cyclic neutropenia was followed for 20 years. After 16 years she developed a permanent agranulocytosis, and lived for nearly four years without neutrophils in the peripheral blood. Neither prednisone, lithium nor leuco- and plasmapheresis had any effect on the neutrophil count. PMID- 3348108 TI - Separate and combined effects of smoking and alcohol abuse in middle-aged men. AB - Alcohol abuse is a major predictor of premature death, and also an independent risk factor for coronary death. Alcoholics are often heavy smokers. In a large primary prevention trial in middle-aged men with 7,495 participants, registration data were used to identify subjects with alcohol problems. Smokers had slightly lower blood pressure and were somewhat leaner than non-smokers, but had slightly higher serum cholesterol levels. Alcohol-registered subjects also tended to have lower blood pressure levels, and higher serum cholesterol. The relative risk of non-fatal myocardial infarction during the follow-up period of 11.8 years was essentially doubled in smokers compared to non-smokers, regardless of registration for alcohol problems. Among the non-alcoholic subjects, the relative risk of coronary death in smokers was double that of non-smokers, whereas the risk in non-smoking alcoholic subjects was not significantly increased. In smoking alcoholics the relative risk was substantially raised to 4.2 (3.0-7.0; 95% c.i.). In multivariate analysis both smoking and alcohol abuse were independently associated with coronary death. A possible mechanism might be through a combination of tobacco-induced coronary arteriosclerosis and the cardiotoxic effects of alcohol. As to total mortality, a smoking non-alcoholic man had a relative risk of dying almost double that of a non-alcoholic non smoker. Among non-smoking alcoholics the risk was three times and, in smoking alcoholics over four times that of the non-alcoholic non-smokers. PMID- 3348109 TI - Alcoholic hepatitis in females. AB - In the period 1970-1984 alcoholic hepatitis was diagnosed by liver biopsy in 52 females. Thirty-six patients with cirrhosis were generally in a worse clinical and biochemical state than those without cirrhosis. Biochemical tests for liver function showed significant improvement from admission to the time of liver biopsy. At follow-up liver function tests were generally better in patients who had stopped drinking alcohol compared to those who continued to do so. The 5-year survival rate was 82% for females without cirrhosis, and 45% for those with cirrhosis (p less than 0.03). Considering the sex-related differences in alcohol abuse in the general population we found no evidence of increased susceptibility to the hepatotoxic effect of alcohol in females. PMID- 3348110 TI - Splenic platelet kinetics and platelet production after major reconstructive vascular surgery. AB - By using 111In-labelled platelets and dynamic gamma camera scintigraphy, platelet production rate and intrasplenic platelet kinetics were determined in 13 patients at 1 and 4 months after aortic reconstructive vascular surgery with implantation of dacron prostheses. A significant decrease in platelet production rate and venous platelet count was recorded over time after surgery. Irrespective of whether the exchangeable splenic platelet pool was estimated from initial recovery of platelet-bound radioactivity or from compartmental analysis, the size of this pool was significantly lower at the first study; a change in intrasplenic platelet transit time accounted for the observed difference. Platelet mean life span increased over time after surgery but the difference between the duplicate studies was not statistically significant. It can be concluded that there is a reduction of platelet production rate and venous platelet count over time after major reconstructive vascular surgery. The early postoperative elevation in the platelet count is mainly the result of an increased platelet production and to a lesser degree due to redistribution of platelets between the splenic platelet pool and general circulation. PMID- 3348111 TI - Plasma lipids and plasma lipoproteins in diabetics with and without proliferative retinopathy. AB - The single most important factor related to the development of diabetic retinopathy is the duration of diabetes. Little is known about the underlying mechanisms, but many factors have been suggested to be involved, among them derangements in plasma lipids and plasma lipoproteins. In the present study we examined the relation between plasma lipids, plasma lipoproteins, and the duration of diabetes in Type I diabetics with and without proliferative retinopathy. The duration of diabetes in the two groups was 12.2 +/- 2.8 and 21.5 +/- 9.0 years, respectively (mean +/- SD; p less than 0.01). Except for moderately low HDL levels, plasma lipid and lipoprotein concentrations were normal in both groups of patients. The levels of lipids and lipoproteins did not correlate with the duration of diabetes. Furthermore, no differences were seen between patients with and without proliferative retinopathy. Thus, the present study does not indicate that plasma lipids and plasma lipoproteins play any major role in the development of diabetic proliferative retinopathy. PMID- 3348112 TI - Choosing death. Withdrawal from chronic dialysis without medical reason. AB - We analyzed patients who died on chronic dialysis because they stopped the treatment, although there was no technical dialysis complication or new medical complication. These patients preferred death to the stress of dialysis. This occurred in 26/1766 (1.5%) patients, and was responsible for 26/704 (4%) of all deaths. We compared these 26 patients to 40 competent patients who discontinued treatment when a medical complication arose. The patients were similar in most respects (age, sex, diagnosis, duration of dialysis, living situation, and type of dialysis) and had the same number of medical complications when starting dialysis. However, the patients who stopped dialysis were more often on home dialysis, 8/24 vs. 3/40 of the other patients (p less than 0.05). Overall, stopping was three times more common in home than in center patients (3.0% vs. 1.1%) (p less than 0.02). Relatives responding to a written interview felt that nurses and social workers but not physicians had been helpful in the difficult time surrounding the patient's decision and death. This study indicates that particularly home dialysis patients are at a high risk of discontinuing dialysis because of the stress of the dialysis procedure. A realistic introduction to and realization of their dialysis problems, better training and better psychological support, particularly from physicians, are necessary to eradicate this avoidable cause of death in chronic dialysis patients. PMID- 3348113 TI - Alcohol and disease. PMID- 3348114 TI - Hyperactivity in children: changing diagnostic criteria. AB - Family physicians are frequently asked to discuss the probable course and outcome of hyperactivity in children. The literature is confusing with regard to the criteria used to define the hyperactivity syndrome. By using updated criteria, physicians can separate hyperactive children into two groups based on the presence or absence of coexisting conduct disorder. When these groups are considered separately, accurate predictions can be made about course and outcome. PMID- 3348115 TI - Mohs micrographic surgery. AB - Mohs micrographic surgery is a precise method of skin cancer removal that offers the highest cure rate and conserves the maximal amount of normal tissue. It is indicated for recurrent tumors and certain primary basal cell and squamous cell carcinomas, but not for small, nonrecurrent, well-defined lesions. The fresh tissue technique permits the use of horizontal frozen sections for the complete microscopic examination of lateral and deep margins. PMID- 3348116 TI - Sexual complications of cancer treatment. AB - The most common sexual dysfunctions in men are erectile impotence, retrograde ejaculation, infertility and loss of libido. Infertility is a function of the drugs and the dosage employed. Alkylating agents are likely to cause prolonged azoospermia. Sexual complications in women include stenosis and atrophy of the vagina, menstrual irregularities, early menopause and decreased libido. PMID- 3348117 TI - Hydrofluoric acid burns. AB - Hydrofluoric acid is used in a variety of industries and poses a considerable medical hazard. The dual mechanism of injury makes hydrofluoric acid burns among the most severe and lethal seen. Prompt treatment with copious irrigation, iced benzethonium or benzalkonium soaks, calcium gluconate gel application and calcium gluconate injections may well prove to be lifesaving. PMID- 3348118 TI - Neurologic complications of herpes zoster. AB - Encephalitis, contralateral hemiplegia and postherpetic neuralgia are the most serious neurologic sequelae of herpes zoster infections. Encephalitis occurs more frequently in the presence of cutaneous dissemination and cranial nerve lesions. Contralateral hemiplegia following herpes zoster ophthalmicus results from vasculitic and thrombotic lesions. The combination of a tricyclic antidepressant and a phenothiazine is the most effective medical treatment for postherpetic neuralgia. PMID- 3348119 TI - The single-patient clinical trial. AB - A single-patient clinical trial is useful in helping the physician decide whether a specific treatment is helpful or harmful in a specific case. The patient's problem must be chronic and stable, and there must be a clearly measurable end point. The close cooperation of the patient, the nurse and the pharmacist is required. In a situation that meets these prerequisites, a properly performed and analyzed single-patient study may be of great benefit. PMID- 3348120 TI - Achalasia. PMID- 3348121 TI - Sudden sensorineural hearing loss. AB - Sudden sensorineural hearing loss has many causes and treatments. The family physician can identify the hearing loss, perform audiometry, identify likely systemic causes and counsel the patient on the prognosis. Most patients are ultimately found to have idiopathic sensorineural hearing loss, and the spontaneous recovery rate is high. If no improvement occurs within one month, evaluation to rule out tumor is recommended. PMID- 3348122 TI - Alcohol, stroke and coronary artery disease. AB - It is widely believed that alcohol use in moderation helps prevent coronary artery disease, but the epidemiologic and experimental support for this concept is mixed and controversial. The controversy has been fueled by new reports on the effect of alcohol on lipoprotein subfractions, on the risk of stroke and on the risk of coronary events. Continued support for the belief that moderate alcohol use has a "protective" effect should be based on stronger evidence than is now at hand. PMID- 3348123 TI - Spontaneous bacterial peritonitis. AB - Characteristics that make spontaneous bacterial peritonitis clinically noteworthy are its increasing prevalence, its tendency to present with few reliable clinical signs and its high mortality rate. Spontaneous bacterial peritonitis almost always occurs in the presence of ascites, and analysis of ascitic fluid is essential for diagnosis. PMID- 3348124 TI - Tricyclic antidepressant blood levels. AB - Plasma concentrations of tricyclic antidepressant drugs vary widely among patients. At routine dosage, unexpectedly low plasma levels are noted in some patients, while toxic levels can occur in others. Individual variability may be due to genetic differences in metabolism or to other factors including drug interactions and poor compliance. Pharmacologic management of depressed patients is often improved when guided by plasma concentration monitoring. PMID- 3348125 TI - Mexican folk remedies and conventional medical care. AB - Despite reports of folk medicine use in all parts of the United States, many physicians are unaware of the extent to which patients use folk medicine and conventional medicine concurrently. A survey of Hispanic patients in West Texas showed that folk medicine was used in 50 percent of the families. Use was not influenced by educational level, employment status or primary language. Most such medicines or rituals are harmless, or possibly helpful, but there are serious exceptions. PMID- 3348126 TI - Outpatient management of COPD. PMID- 3348127 TI - Use of mammograms to detect breast cancer. PMID- 3348128 TI - Guidelines for school programs to prevent the spread of AIDS. PMID- 3348129 TI - Cost and compliance. PMID- 3348130 TI - Exclusions for organ and tissue donors. PMID- 3348131 TI - Drug testing of pharmacy graduates: an idea whose time should not come. PMID- 3348132 TI - Policy forum. An interview with Rep. Mickey Leland. PMID- 3348133 TI - Use of nonsteroidal anti-inflammatory drugs in a health maintenance organization. PMID- 3348134 TI - Pharmacy practice. Fulfilling the mission. PMID- 3348135 TI - Sustained-release isosorbide mononitrate (50 mg): optimization of a once-daily dosage form for long-term treatment of angina pectoris. AB - A capsule formulation containing 50 mg of isosorbide mononitrate has been developed, 30% of which is in a nonsustained-release form to ensure rapid attainment of initial plasma levels. The remaining 70% is in a sustained-release form that ensures a long-lasting effect and the convenience of once-daily dosing. This formulation of sustained-release isosorbide mononitrate (Elantan LA 50 mg) provides plasma levels greater than 100 ng/ml for 17 hours after oral administration. For the remaining 7 hours, the nitrate plasma level ranges between 50 and 100 ng/ml. PMID- 3348136 TI - More rapid relief of pain with isosorbide dinitrate oral spray than with sublingual tablets in elderly patients with angina pectoris. AB - To evaluate the possibility of improving clinical practice in the treatment of angina pectoris, the duration of relief of pain with isosorbide dinitrate (ISDN) oral spray and sublingual tablets were compared in elderly patients with chronic stable angina pectoris. Nine patients (mean age 67 years) were studied in a randomized crossover trial. The patients underwent bicycle ergometry, which resulted in typical chest pain associated with electrocardiographic ST-segment depression in all 9. The patients received ISDN oral spray or sublingual tablets immediately on termination of exercise. At least 6 hours later another ergometry test was performed and the patients were crossed over to the other drug. ISDN spray relieved pain in all patients at a mean duration of 61.6 +/- 24.4 seconds after administration, whereas the duration of relief of pain by ISDN sublingual tablets was 112.4 +/- 70 seconds. The difference was highly significant (p less than 0.0005). It is concluded that clinical practice of treatment of angina pectoris in the elderly can be improved by using ISDN oral spray rather than sublingual tablets. The spray is effective at twice the rapidity of the sublingual tablet. PMID- 3348137 TI - Emergency treatment of severe cardiogenic pulmonary edema with intravenous isosorbide-5-mononitrate. AB - Intravenous isosorbide-5-mononitrate (IS-5-MN) was administered to 24 patients, mean age 73, with severe respiratory distress after pulmonary edema and acute left heart failure. The condition was due to ischemic cardiopathy in 18 patients (4 with acute myocardial infarctions), congestive cardiomyopathy in 3, hypertensive cardiopathy in 2, and mitral valvular disease in 1. Therapy consisted of an intravenous (i.v.) bolus dose of IS-5-MN, followed by a continuous infusion (mean 8 mg/hour over 24 hours) of i.v. furosemide and additional oxygen. Clinical data were recorded as well as blood gas values and repeated chest radiographs. All patients survived and improved markedly; only 6 needed mechanical ventilation. Most patients had fast respiratory relief, with no untoward reaction, except a brief decrease of blood pressure in a ventilated patient taking morphine. These data indicate that i.v. IS-5-MN is effective and safe for the management of severe acute cardiogenic pulmonary edema. PMID- 3348138 TI - Acute effect of various doses of isosorbide-5-mononitrate on hemodynamic and exercise performance in coronary artery disease. AB - The optimal dose of nitrates is still controversial, as chronic usage of too high a dose may result in a decrease in vascular response. The dose should be determined to reduce preload acutely, and not to decrease the activity during chronic therapy. To determine this dose, 50 patients with angiographically confirmed coronary artery disease were studied. The effects on heart rate and mean systemic and pulmonary arterial pressures at rest and during exercise, and work capacity and duration were measured. The patients were classified into 5 groups, receiving placebo or isosorbide-5-mononitrate, 5, 10, 20 and 50 mg, respectively, as a single oral dose. Placebo had no effect on the measured parameters. All doses of isosorbide-5-mononitrate reduced mean pulmonary arterial pressure: 10 mg--by 16% at rest and 24% during exercise; 20 mg--24% and 34%, respectively (a near maximal effect); and 50 mg--27% and 38%. Similar results were found also for work capacity: 10 mg increased work capacity by 33%; 20 mg- 79%; and 50 mg--56%. Thus, the therapeutically optimal single dose is about 20 mg. Higher doses produce no additional benefit and increase the risk for tolerance development. PMID- 3348139 TI - Increased exercise tolerance and reduced duration of ischemia after isosorbide dinitrate oral spray in angina pectoris. AB - The prophylactic and therapeutic anti-ischemic efficacy of isosorbide dinitrate (ISDN) oral spray was assessed in 10 patients with coronary artery disease and stable angina pectoris. The patients entered a randomized crossover study of ISDN spray and placebo, involving bicycle exercise testing. Each patient underwent 2 exercise tests at least 4 hours apart. Immediately before initiation of exercise they received either ISDN spray or placebo and crossed over during the other test. ISDN spray delayed the onset of anginal pain by about 40%, from a mean of 5.1 +/- 1.4 minutes with placebo to 7.2 +/- 1.3 minutes with the active drug (p less than 0.001). Time of onset of ST-segment depression was also significantly prolonged, from 7.1 +/- 1.5 minutes with placebo to 10.2 +/- 1.2 minutes with ISDN (p less than 0.001). The patients achieved a higher double product at onset of pain with ISDN than with placebo. The drug also reduced the time of disappearance of pain after discontinuation of exercise from 3.2 +/- 0.7 to 2.1 +/- 0.8 minutes (p less than 0.001), and the time of disappearance of electrocardiographic changes from 4.2 +/- 0.6 to 2.5 +/- 0.8 minutes (p less than 0.005). These findings indicate that oral ISDN spray is an effective prophylactic for exercise-induced angina. Its rapid onset of action makes it especially suitable for usage immediately before exercise. PMID- 3348140 TI - Intravenous isosorbide dinitrate during open-heart surgery and its role in the treatment of right-sided congestive heart failure. AB - Recent awareness of the importance of the functional integrity of the right ventricle and the effect of raised pulmonary vascular resistance on cardiac output after cardiopulmonary bypass has focused attention on means of protecting right ventricular myocardium and reducing right ventricular afterload during open heart surgery. A study of the acute effects of bolus intravenous isosorbide dinitrate (ISDN) has shown that after cardiopulmonary bypass, bolus intravenous ISDN produced highly significant (p less than 0.001) decreases in mean pulmonary arterial pressure (13%), pulmonary vascular resistance (23%) and the ratio of pulmonary to systemic vascular resistance (20%), indicating that active pulmonary vasodilation had occurred in the absence of other hemodynamic changes. The results suggest that possibly the acute effect of low-dose ISDN after cardiopulmonary bypass is predominantly exerted on the right ventricular afterload if systemic arterial pressure is not elevated. Two different clinical situations are described in which intravenous ISDN proved beneficial, one being acute pulmonary hypertension after protamine sulphate and the second being acute right-sided congestive heart failure with systemic hypotension unresponsive to conventional therapeutic measures. Thus, ISDN may prove a useful agent for alleviating right ventricular dysfunction at a time of not infrequent cardiovascular instability, the period after bypass. PMID- 3348142 TI - Effects of isosorbide dinitrates intravenously in high doses over a short period in anterior acute myocardial infarction. AB - The effects of intravenous isosorbide dinitrate administered in high doses over a short period of time in 17 patients (14 men, 3 women, mean age 67 years) with anterior wall acute myocardial infarction were evaluated. Patients were classified into 2 groups based on the electrocardiographic pattern of acute ischemia. Patients presented with anterior acute myocardial infarction; an electrocardiographic pattern of third-degree ischemia demonstrated a more favorable electrocardiographic and radionuclear angiographic evolution than similar patients who presented with an electrocardiographic pattern of second degree ischemia. PMID- 3348141 TI - Effects of long-term treatment with 120 mg of sustained-release isosorbide dinitrate and 60 mg of sustained-release nifedipine on myocardial perfusion. AB - Forty patients with coronary artery disease and scintigraphically proven myocardial ischemia were randomized into 2 groups receiving 4 weeks of treatment with either 120 mg of isosorbide dinitrate (ISDN) release or 60 mg of nifedipine release. Control exercise testing and myocardial scintigraphy were continued until anginal pains occurred, and repeated at identical individual workloads at the end of the 4 weeks of drug therapy. Myocardial scintigrams were evaluated by quantitative recording of counts in 60 segments/frame. Twenty patients in the ISDN group (group I) exhibited 47 significantly ischemic areas. The remaining 20 patients (group II), treated with nifedipine, had 50 ischemic areas before therapy. In the ischemic areas in group I, there was a mean difference of 30.9% between counts at rest and during exercise in the pretreatment period, and a difference of 18.1% after therapy (39.0%). In group II, the pretreatment difference was 28.8%, decreasing to 20.6% after therapy (17.8%). Both groups of patients were subsequently subdivided into 3 subsets: (1) significantly improved perfusion, (2) significant worsening, and (3) unchanged myocardial perfusion. Group I had 59.5% of areas with significant improvement and 10.6% of areas with significant worsening. In 29.7% of the areas, the findings were unchanged. Group II had improvement in 40% of areas, of significantly worsened areas in 6%, and unchanged areas in 54%, in both groups myocardial ischemia was reduced by therapy, but ISDN improved myocardial perfusion to a considerably greater extent than did nifedipine. PMID- 3348143 TI - Spontaneous regeneration of older dystrophic muscle does not reflect its regenerative capacity. AB - Young dystrophic (dy) murine muscle is capable of "spontaneous" regeneration (i.e., regeneration in the absence of external trauma); however, by the time the mice are 8 weeks old, this regeneration ceases. It has been suggested that the cessation of regeneration in dystrophic muscle may be due to exhaustion of the mitotic capability of myosatellite cells during the early stages of the disease. To test this hypothesis, orthotopic transplantation of bupivacaine treated, whole extensor digitorum longus muscles has been performed on 14 to 16-week-old 129 ReJ/++ and 129 ReJ/dydy mice. The grafted dystrophic muscle is able to produce and maintain for 100 days post-transplantation 356 +/- 22 myofibers, a number similar to that found in age-matched dystrophic muscle. The ability of old dystrophic muscle to regenerate subsequent to extreme trauma indicates that the cessation of "spontaneous" regeneration is due to factor(s) other than the exhaustion of mitotic capability of myosatellite cells. Moreover, there is no significant difference in myosatellite cell frequencies between grafted normal and dystrophic muscles (100 days post-transplantation). Myosatellite cell frequencies in grafted muscles are similar to those in age-matched, untraumatized muscles. While grafting of young dystrophic muscle modifies the phenotypic expression of histopathological changes usually associated with murine dystrophy, grafts of older dystrophic muscle show extensive connective-tissue infiltration and significantly fewer myofibers than do grafts of age-matched normal muscle. As early as 14 days post-transplantation, it is possible to distinguish between grafts of old, normal and dystrophic muscles. It is suggested that the connective tissue stroma, present in the dystrophic muscle at the time of transplantation, may survive the grafting procedure. PMID- 3348144 TI - Comparison of components of the testis interstitium with testosterone secretion in hamster, rat, and guinea pig testes perfused in vitro. AB - Components of the testis and cytoplasmic organelles in Leydig cells were quantified with morphometric techniques in hamster, rat, and guinea pig. Testosterone secretory capacity per gram of testis and per Leydig cell in response to luteinizing hormone (LH) (100 ng/ml) stimulation was determined in these three species from testes perfused in vitro. Numerous correlations were measured among structures, and between structures and testosterone secretion, to provide structural evidence of intratesticular control of Leydig cell function. Testosterone secretion per gm testis and per Leydig cell was significantly different in the three species: highest in the guinea pig, intermediate in the rat, and lowest in the hamster. The volume of seminiferous tubules per gm testis was negatively correlated, and the volumes of interstitium, Leydig cells, and lymphatic space per gm testis were positively correlated with testosterone secretion. No correlations were observed between volumes of blood vessels, elongated spindleshaped cells, or macrophages per gm testes and testosterone secretion. The average volume of a Leydig cell and the volume and surface area of smooth endoplasmic reticulum (SER) and peroxisomes per Leydig cell were positively correlated, and the volume of lysosomes and surface area of inner mitochondrial membrane per Leydig cell were negatively correlated with testosterone secretion. No correlations were observed between volume and surface area of rough endoplasmic reticulum (RER), Golgi apparatus, and lipid, and volume of ribosomes, cytoplasmic matrix, and the nucleus with testosterone secretion per Leydig cell. These results suggest that Leydig cell size is more important than number of Leydig cells in explaining the difference in testosterone-secreting capacity among the three species, and that this increase in average volume of a Leydig cell is associated specifically with increased volume and surface area of SER and peroxisomes. An important unresolved question is what is the role of peroxisomes in Leydig cell steroidogenesis. PMID- 3348145 TI - Amianthoid (asbestoid) transformation: electron microscopical studies on aging human costal cartilage. AB - The present study reports on the fine structure of human costal cartilage at different ages in order to obtain information on the morphogenesis of amianthoid fibers. Our results reveal an overall increase of collagen fibril diameter with increasing age, even in areas with no signs of amianthoid transformation. Ultrastructural evidence is presented that this increase in diameter is due to a gathering of the preexisting collagen fibrils. The age-related change in collagen fibril diameter is paralleled by changes in the composition and ultrastructural appearance of cartilage proteoglycans (as revealed by acridine orange staining). Acridine-orange-positive filaments indicative for proteoglycans are markedly reduced in size with advancing age in centrally located regions of costal cartilage. Treatment with testicular hyaluronidase previous to acridine-orange staining leaves these small proteoglycan filaments unaffected. By contrast, the filaments visible after acridine-orange staining in the extracellular matrix near to the perichondrium are susceptible to hyaluronidase treatment. Infrequently, a sharp increase in collagen fibril diameter can be observed in territorial matrix areas of degenerating chondrocytes. This observation is conspicuous at ages of 10 and 20 years. Amianthoid transformation is characterized by the appearance of collagen fibrils strictly arranged in parallel. These amianthoid fibers are embedded in a matrix rich in small acridine-orange-positive filaments similar to the proteoglycan filaments observed in centrally located matrix regions. It can be concluded that extensive remodelling not only of the collagen fibrils but also of the cartilage proteoglycans is involved in the development of amianthoid transformation. PMID- 3348146 TI - Developmental heterogeneity of mesenchymal glycosaminoglycans (GAG) distribution in chick embryo lung anlagen. AB - The presence and distribution of mesenchymal components in the extracellular matrix during lung development in the chick embryo (from 5 1/2/6 to 18 incubation days) has been examined histochemically. Attention is focused mainly on glycosaminoglycans (GAG). Morphological reconstructions show three main stages: first (5 1/2/6-8 days), formation of 2nd-order branching; second (9-12 days), proliferation of parabronchi and third (from 13th day on), formation of air capillaries. In the first phase, hyaluronic acid (HA) prevails around the mesobronchus, but chondroitin sulfate (CS) dominates the 2nd-order branches. Basement membranes of 2nd-order branches are strongly positive for sulphated GAG. In the second phase, CSA increases in the ground substance of mesenchyme. This increase is irregular, being smaller in older areas (mesobronchus, branches of 2nd order) and larger in the more recent parabronchi, which extend into the lateral and dorsal areas of the rudiment. An increase in both sulfated GAG and glycoprotein (GP) occurs in basement membranes. In the third phase, GAGs are uniformly distributed in the mesenchymal septa and around the interlobular vascular network. This concentration decreases while the GP concentration increases. Basement membranes around every branch of the 1st, 2nd, and 3rd orders possess large quantities of GP. Mesenchymal GAG occurs in every stage of lung development, temporally correlating with the morphogenesis and differentiation of epithelium. Our results provide necessary information, which has not been available so far. Experimental studies specifically designed to clarify the developmental significance of such a heterogeneous distribution may be interpreted in the light of this information. PMID- 3348147 TI - Immunocytochemical study using a GABA antiserum for the demonstration of inhibitory neurons in the rat locus ceruleus. AB - The localization of GABA-like immunoreactivity in the locus ceruleus of rats was studied by the peroxidase-antiperoxidase (PAP) method using a purified antibody raised against GABA applied to paraffin sections, with counterstaining by cresylecht violet, and to floating sections for preembedding immunoelectron microscopy. A few medium-sized and some small neurons showed GABA-like immunoreactivity in both nuclei and perikarya. The preferential localization of these immunopositive neurons in the marginal parts of the locus ceruleus suggests that they are inhibitory local circuit neurons located between this center and the afferent fiber systems. Some of the immunoreactive neurons displayed homogeneous and heterogeneous "paired cells" patterns. Occurrence of the GABA GABA interaction is indicated. Immunopositive bouton forms are located close to every positive and negative neuron. Electron microscopy confirms GABA-like immunoreactivity in both medium-sized and small neurons of the locus ceruleus and demonstrates that immunoreactive boutons are axosomatic and axosoma spine symmetric synapses on immunopositive and immunonegative cell bodies. These immunocytochemical results support the existence of inhibitory interneurons in the locus ceruleus. PMID- 3348148 TI - Development of the choroid plexus anlage and supraependymal structures in the fourth ventricular roof plate of human embryos: scanning electron microscopic observations. AB - The developing anlage of the choroid plexus and supraependymal structures in the fourth ventricular roof plates of nine normal human embryos ranging from Carnegie stages 14 to 19 were investigated with scanning electron microscopy. In the human embryos at stage 18, the first semimacroscopic choroidal anlage developed in the form of bilateral evaginations that ran dorsomedially and caudally from the bilateral corners of the rhombencephalon. The anlage became evident with even smaller and parallel ridges in the embryo at stage 19. Embryos at earlier stages exhibited surface membrane modifications such as convexity, microvilli, cilia, and spherical protrusions at the middle one-third of the rhombencephalon, which corresponded to the future choroidal anlage region. Two morphologically different groups of supraependymal cells (SE cells) were elucidated throughout the stages examined. Type 1 SE cells has spindle or tear-drop-like bodies, frequently with one or more long cytoplasmic processes. Type 2 SE cells were globular, with numerous fine pseudopodial processes. Type 1 SE cells were distributed mainly at the future choroidal anlage regions or on the anlage itself and were less frequently located at the rostral end of the roof. We found no general pattern in the distribution of type 2 SE cells. Supraependymal fibers (SE fibers) were seen as fine processes that were distributed similarly to type 1 SE cells and extended transversely for a long distance. PMID- 3348149 TI - Three-dimensional canine renovascular structure and circulation visualized in situ with the dynamic spatial reconstructor. AB - The dynamic spatial reconstructor--a unique, high speed, volume-scanning, X-ray computed tomographic imaging system--was utilized to examine canine renovascular anatomy and renal circulation in situ. In each of the four kidneys examined in this study initial scans were done during bolus injections of angiographic contrast material into the renal artery. A subsequent scan was then performed following an injection of methyl-methacrylate-based casting compound that had been contrast enhanced with ethiodol. After the scans, each kidney was removed, and its parenchyma was digested in potassium hydroxide to expose the vascular cast. Comparison of casts with their reconstructed images and with images obtained during injection of contrast material showed that interlobar arteries and occasionally arcuate arteries could be clearly detected. Although discrete vessels less than 1 mm in diameter could not be resolved, dynamic changes in parenchymal distribution of density during passage of contrast material allowed interpretation of flow through the multiple capillary beds of the kidney. Such analysis indicated that maximal density was in the outer-middle zone of the cortex throughout the duration of the scan. Analysis of artery-to-vein transit time showed arrival of contrast material in the renal vein as soon as 3 sec, and continuation for longer than 8 sec, after the renal artery bolus. In conclusion, renal circulation in the dog can be discretely visualized with the dynamic spatial reconstructor up to the level of the arcuate arteries; however, capillary flow as a whole can be followed through the cortex, and the results suggest the presence of both rapid and slow components of peritubular circulation. PMID- 3348150 TI - The development of the sexually indifferent gonad in the prosimian, Galago crassicaudatus crassicaudatus. AB - The morphogenesis of the sexually indifferent gonad of the primate Galago crassicaudatus crassicaudatus was studied by high-resolution light microscopy and electron microscopy in 15 embryos aged 26 to 33 days. Onset of gonadal development follows the morphogenesis of the mesonephros by a conspicuous interval and is identified as the time when the first primordial germinal cells arrive in the region ventral to the central third of the mesonephros; this is followed by intense proliferation of the coelomic mesothelial cells lining the area. They become organized into short piles that deepen in the underlying mesenchyme, enclosing the germinal cells in the process. Rapidly, the piles become confluent forming a compact mass, the gonadal blastema, which is soon cleaved into gonadal cords by stroma and vascular lacunae. The mesonephros becomes involved in the morphogenesis of the gonad only in late stages of development when anatomic continuities become established between the capsules of its regressing glomeruli and the elongating gonadal rete cords. These observations show that in the Galago the somatic cells of the gonadal blastema, i.e., the precursors of the definitive testicular and ovarian sustentacular cells, derive from the coelomic mesothelium in contrast to other mammals, e.g., ruminants and rodents, where they are of mesonephric derivation. This important point is discussed in light of the differences that exist among species with regard to the structural complexity, functionality, and stages of differentiation/involution of their mesonephroi on the one hand, and the time of gonadal development on the other. PMID- 3348151 TI - Effects of repeated weight loss and regain on body composition in obese rats. AB - To test the hypothesis that repeated loss and gain of weight through dieting will result in increasing fatness, 200-g female Sprague-Dawley rats were castrated and allowed to become obese on a high-fat diet for 6 wk. Two successive periods of severe food restriction (50% maintenance for 28 d and 25% maintenance for 21 d) were each followed by ad libitum refeeding on the high-fat diet until control body weights were attained. Percent body fat was determined indirectly from body density and total-body water at the end of each cycle. Restricted rats gained weight and attained control body weights on ad libitum feeding without overshooting these weights, and percentage body fat was not different from that of controls at the end of either cycle (cycle 1 22.3 +/- 1.7 vs 23.8 +/- 1.7%; cycle 2 19.0 +/- 1.1 vs 21.6 +/- 0.8%). Repeated cycles of weight loss and regain do not produce increased body fatness or decreased rate of weight loss in ovariectomized rats. PMID- 3348152 TI - Effect of different caloric loads in human jejunum on meal-stimulated and nonstimulated biliopancreatic secretion. AB - The effects on biliopancreatic secretion of two caloric loads (1.3 and 3.3 kcal/min of Realmentyl: proteins 18%, lipids 27%, carbohydrates 55%), infused into the jejuna of 10 healthy men, were compared with those of a control solution. In one set of experiments (six subjects) when biliopancreatic secretion was not stimulated before infusion, the rate 1.3 kcal/min resulted in mild stimulation whereas the rate 3.3 kcal/min brought about an inhibition of biliopancreatic secretion. In another set of experiments (six subjects) when biliopancreatic secretion was stimulated by ingestion of an homogenized meal (400 mL, 490 kcal) 1 h before the start of infusion, both loads resulted in strong inhibition of pancreatic secretions, the effect being more pronounced with the high caloric load. PMID- 3348154 TI - Effects of sucrose vs starch diets on in vivo insulin action, thermogenesis, and obesity in rats. AB - High intake of simple sugars is generally seen as a detrimental factor in the etiology of both obesity and insulin resistance. To examine possible deleterious effects of sucrose, independent of changes in energy intake, rats were fed equal amounts of high-sucrose or high-starch diets over 4 wk. Energy expenditure was assessed by open-circuit respirometry and carcass analysis. In vivo insulin action in individual tissues was assessed with the hyperinsulinemic (1 nmol/L), euglycemic clamp combined with tracer glucose and 2-deoxyglucose administration. Whole-body glucose disposal was impaired by sucrose feeding (clamp glucose infusion rate of 77 +/- 4 vs 124 +/- 6 mumol/[kg.min], p less than 0.001, for sucrose and starch, respectively) because of a major impairment of insulin action at the liver with a smaller contribution from peripheral tissues. Sucrose feeding affected neither basal or stimulated energy expenditure nor accumulation of body fat. In conclusion, sucrose feeding produces a major impairment of insulin action, predominantly because of an effect at the liver. PMID- 3348153 TI - Energy intake and other determinants of relative weight. AB - The relationships of relative weight to energy intake and to physical activity were studied among 141 females aged 34-59 y. As observed in previous studies Quetelet index (wt/ht2) was inversely related to energy intake (r = -0.11). However, obese women tended to be older (r = 0.16), exercise less (r = -0.30), and drink less alcohol (r = -0.16) than nonobese women. Older women had lower energy intake (r = -0.23) and exercised less (r = -0.12) than younger women. Energy intake and physical activity were positively related (r = 0.23). After adjustment for age, physical activity, alcohol, and smoking, the inverse correlation between relative weight and energy intake was significantly reduced (p = 0.04) from r = -0.11 to r = -0.02. Obese women reported higher intakes of total fat, and relative weight was significantly correlated with intakes of total fat (r = 0.20) and saturated fatty acids (r = 0.16). These data highlight the importance of considering factors that may confound the relationship between energy intake and obesity, and they suggest that fat intake may play a role in obesity that is independent of total energy intake. PMID- 3348155 TI - All yogurts are not created equal. AB - Because of autodigestion of lactose by its endogenous bacteria, the lactose in yogurt is better absorbed than other sources of lactose in lactase-deficient subjects. To investigate possible differences among brands of yogurt in this autodigesting capacity, we challenged eight lactose-malabsorbing subjects with 20 g oral lactose and three different brands of yogurt (Borden, Dannon, and Royal Maid). As a quantitative measure of carbohydrate absorption, end-alveolar breath samples were collected for 8 h and assayed for hydrogen gas. Symptoms were scored by questionnaire every 30 min for 8 h. The cumulative breath H2 and the area under the discontinuous curve of breath-H2 concentration decreased relative to lactose results after ingestion of Dannon and Royal Maid but not after Bordon yogurt. no correlation of symptoms with the degree of carbohydrate malabsorption was demonstrated. We conclude that the lactase activity of yogurt cultures varies among brands. PMID- 3348156 TI - Vitamin A analogs as tests for liver vitamin A status in the rat. AB - Two chlorinated retinol analogs (Ro 11-0503 and Ro 11-8284) were assayed in rat serum and correlated to retinol in liver. Rats were fed a retinol-free diet to deplete their liver stores, then repleted with 0.5, 1.0, 3.0, and 10.0 mg retinyl palmitate/kg diet. Rats were given intraperitoneal injections of the analog then killed after an additional week on the diets. Analogs were measured by HPLC. The relative abundance of both analogs in serum was inversely correlated with the amount of retinyl palmitate in the liver. Serum analog concentrations may be useful as indications of liver retinol stores. PMID- 3348157 TI - Decreased vitamin B-6 status of submariners during prolonged patrol. AB - We investigated the effects of a 3-mo submarine patrol upon several vitamin B-6 indices in 23 male submariners. While on patrol, 12 subjects received a multivitamin-mineral supplement that provided 0.5 mg/d vitamin B-6 and 11 subjects received a placebo. The concentrations of plasma pyridoxal 5'-phosphate, total vitamin B-6, and urine 4-pyridoxic acid were significantly reduced during the patrol in both the placebo and the supplemented groups. The hematocrit of both groups also decreased by approximately 10% during the patrol and was not restored to prepatrol concentrations until several weeks postpatrol. Mood depressions, as measured by the Beck inventory and the depression adjective check list, were most pronounced during the 30 d before and at the beginning of the patrol. These depression measures did not correlate with the vitamin B-6 status indices, indicating that the mood depressions during a patrol do not appear to be related to the vitamin B-6 status of the submariners. PMID- 3348158 TI - Vitamin E and relationships among tocopherols in human plasma, platelets, lymphocytes, and red blood cells. AB - Plasma, RBC, platelets, and lymphocytes from human subjects on graded intakes of vitamin E were analyzed for tocopherols to determine which humoral compartment most closely followed changes in the dietary intake. Relative merits of the various blood elements to reflect changes in vitamin E intake were calculated by the sensitivity concept of Mandel and Stiehler (ie, rate of change of tocopherol levels with dose divided by the standard deviation). Sensitivities of alpha tocopherol levels of the various blood components to vitamin E intake decreased in the order platelets greater than RBC greater than plasma lipids greater than plasma greater than lymphocytes. Changes in tocopherol levels in platelets most closely followed changing dietary intakes of vitamin E when compared with data from RBC, lymphocytes, and plasma. Furthermore, for studying the effects of diets on vitamin E status, tocopherol levels of platelets appear to be a better measure than tocopherol levels of either RBC, lymphocytes, or plasma lipids. PMID- 3348159 TI - Vitamin K deficiency from dietary vitamin K restriction in humans. AB - Vitamin K is required for the maintenance of normal hemostatic function. Ten college-aged male subjects chose diets restricted in vitamin K content for 40 d. Median phylloquinone intakes based on analysis of food composites dropped from 82 micrograms/d during the prestudy period to 40 and 32 micrograms/d at d 9 and 27 of dietary restriction, respectively. Serum phylloquinone concentrations fell from a mean of 0.87 to 0.46 ng/mL during a 21-d period of vitamin K restriction. Supplementation with 50 micrograms phylloquinone/d for 12 d increased serum phylloquinone to 0.56 ng/mL, and supplementation with 500 micrograms phylloquinone/d increased serum phylloquinone to 1.66 ng/mL. Vitamin K restriction resulted in alterations in a functional clotting assay that detects undercarboxylated prothrombin species in plasma and in a decrease in urinary gamma-carboxyglutamic acid. Supplementation with either 50 or 500 micrograms of phylloquinone restored both these indices to near normal values. These data are consistent with a human dietary vitamin K requirement of approximately 1 microgram/kg body wt/d. PMID- 3348161 TI - Iron supplementation and physical growth of rural Indonesian children. AB - The effect of oral iron supplementation on blood Fe levels and physical growth in 119 rural Indonesian school children was assessed in this double-blind study. The children were classified into anemic and normal groups according to their initial hemoglobin and transferrin saturation levels and were randomly assigned to either Fe or placebo treatment for 12 wk. Hematological, anthropometric, and morbidity data were collected before and after the treatment period. Before treatment, anemic subjects were smaller and had higher morbidity than normal subjects. Treatment with 10 mg ferrous sulfate.kg-1.d-1 for 12 wk resulted in a significant improvement in anemic subjects' hematological status, growth velocity, and level or morbidity. PMID- 3348160 TI - Riboflavin metabolism in the hypothyroid newborn. AB - In the hypothyroid rat the flavin adenine dinucleotide (FAD) content of the liver is similar to that observed in rats maintained on a riboflavin-deficient diet. Thyroxine regulates the enzyme flavin kinase. Human adults with hypothyroidism have levels of erythrocyte glutathione reductase (EGR), an FAD-containing enzyme, in the range indicative of riboflavin deficiency, which can be corrected with thyroxine therapy. In the present study six newborns with severe congenital hypothyroidism because of athyrosis, ectopic thyroidism, or congenital hypothyroidism with Down's syndrome had normal levels of EGR, and treatment with thyroxine had no effect on these levels. PMID- 3348163 TI - Zinc, copper, and nitrogen balances during bed rest and fluoride supplementation in healthy adult males. AB - The effects of bed rest and fluoride supplementation on zinc, copper, and nitrogen balances and Zn and Cu serum levels were measured in 15 healthy males. Subjects aged 19-54 y remained on a metabolic research ward for 10 wk. During weeks 1-5, subjects were ambulatory. During wks 6-10 they remained in continuous bed rest. During weeks 3-10 nine subjects received 10 or 20 mg F/d as sodium fluoride. Daily urine and weekly fecal composites were made and biweekly fasting blood samples were taken. Dietary intakes were 1.40 +/- 0.17 mg Cu/d (22.0 +/- 2.7 mumol Cu/d), 10.82 +/- 0.49 mg Zn/d (165.6 +/- 7.6 mumol Zn/d), and 14.27 +/- 0.23 g N/d (1019 +/- 16 mmol N/d). Bed rest increased urinary Zn and N excretions and fecal Zn excretions and decreased Zn balance (p less than 0.05) whereas Cu balance was unchanged. During bed rest, F supplementation increased Zn and N balances compared with untreated control subjects (p less than 0.05). These results are compatible with bone and muscle atrophy during bed rest and increased bone formation with F supplementation. PMID- 3348162 TI - Responses of sodium balance, blood pressure, and other variables to sodium loading in Papua New Guinea highlanders. AB - For determination of the responses of sodium balance, blood pressure, and other relevant variables to Na loading in people with a low intake of Na, 10 male Papua New Guinea highland subjects were given additional Na at two levels (128 and 256 mmol/d) for 10 d after a 3-d control period of low-Na diet. Na loading caused a marked positive balance of Na, decreases of aldosterone concentration and renin activity in the plasma, and a decrease of urinary aldosterone excretion. The blood pressure, particularly that measured at noon, increased in the latter half of the Na-loading period, the increase being significant in the group given 256 mmol of sodium daily: the systolic and diastolic blood pressure increased from 92 +/- 8 over 56 +/- 7 mm Hg in the control period to 102 +/- 7 over 60 +/- 4 mm Hg in the latter half of the test period (p less than 0.05). PMID- 3348164 TI - Dietary intakes and biochemical indicators of nutritional status in an elderly, institutionalized population. AB - A dietary and biochemical assessment of the nutritional status of 260 elderly men and women, 60-101 y (average 80.5 y), was conducted in 15 long-term-care facilities in the Boston area. Subjects were free of clinically apparent terminal or wasting illness. Nutrient intakes were comparable to those in a simultaneously studied free-living population as were most biochemical markers of nutrient status. Although no specific nutrient deficiencies were identified, blood levels of vitamin A and retinol-binding protein in males and of zinc in both sexes were lower in this institutionalized group than in the free-living subjects. Hematologic indices, albumin, prealbumin, and transferrin levels were also lower than in noninstitutionalized elderly populations. These differences may reflect the greater prevalence of chronic diseases and medication use in a long-term-care population. However, there is no evidence that institutionalization in itself leads to impairment of nutritional status. PMID- 3348165 TI - Three limitations of body mass index. PMID- 3348167 TI - The adolescent varicocele. A histopathologic study of 13 testicular biopsies. AB - Testicular varicocele, the most common cause of male infertility, frequently presents in early adolescence. To determine whether testicular damage occurs early in the natural history of varicocele, testicular biopsy specimens from 13 patients, 13 to 18 years of age (mean age, 15.5 years), were studied. The biopsies were compared with testicular tissue from six normal control subjects 15 to 28 years of age (mean age, 23.2 years). Nine of the patients with varicoceles (69.2%) demonstrated some degree of tubular sclerosis. Ultrastructural study demonstrated that the tubular sclerosis was due to collagen deposition by fibromyocytes in the peritubular sheath. Premature germ cell sloughing was present in greater than 50% of tubules examined in all but one biopsy. Six patients (46%) demonstrated small vessel sclerosis. Quantitation of the germinal epithelium revealed that the mean germ cell/Sertoli cell ratio and the percentage of germ cells present as late stage forms (secondary spermatocytes, spermatids and spermatozoa) were significantly reduced in the varicocele group. The testes of two patients exhibited severe hypospermatogenesis approaching germ cell aplasia. None of these changes were seen in the control group. The authors conclude that pathologic changes in the testes of patients with varicoceles are found at or soon after puberty. The histopathologic features include peritubular sclerosis, small vessel sclerosis, premature germ cell sloughing, and variable degrees of hypospermatogenesis. PMID- 3348166 TI - Dendritic/Langerhans cells and prognosis in patients with papillary thyroid carcinomas. Immunocytochemical study of 106 thyroid neoplasms correlated to follow-up data. AB - Paraffin sections of 106 primary thyroid carcinomas were the subject of an immunocytochemical study to determine the density of infiltrates of S-100 protein positive dendritic/Langerhans cells (LC), lysozyme-positive histiocytes, and LCA positive lymphocytes. Evidence of dense infiltrates of LCs was found only in the majority of papillary thyroid carcinomas (PCs). The determination of the quantity of LCs proved to be a highly effective means of assessing the prognosis of these tumors. Irrespective of other morphologic and clinical features, no single instance of death resulting from cancer occurred among 23 PCs with dense LC infiltrates (including 6 tumors of stage pT4), while 9 of 53 (17%) of the remaining patients ultimately died from thyroid cancer. On the other hand, the degree of histiocytic and lymphocytic infiltrations was not associated with a distinct biologic behavior neither among PC nor among the remaining thyroid carcinomas. These findings suggest that LCs may play an important role in the immunologic defense mechanisms of the host against the tumor only in the papillary type of thyroid cancer. PMID- 3348168 TI - Lymphocyte activation in oral lichen planus in situ. AB - The current study evaluated the activation of T-cell mediated cellular immune response in the oral lesions in lichen planus (OLP). Analysis was made of the ultramorphology, lymphocyte activation marker expression, DNA synthesis, and gamma-interferon production of the inflammatory cells in OLP lesions. According to these four different aspects of lymphocyte activation, only a minor fraction, 5% at the most, of all T-cells in situ were activated. This minor fraction, however, not the resting T-cells without these signs of activation, may decide the outcome of the local immune-inflammatory process in OLP. Of the inflammatory cells in situ, however, 81 +/- 5% were Ia positive. This finding may be the result of an Ia inducing capacity of the gamma-interferon produced locally by the activated T-cells. PMID- 3348169 TI - Automation of routine coagulation testing using a random access centrifugal analyzer. AB - The results are reported of a clinical and laboratory evaluation of the use of a random-access centrifugal analyzer linked to a personal computer in the management of the routine workload of a hemostasis laboratory. Over a three-month period, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT), and derived fibrinogen (Fib) were performed on a total of 929 samples. Included in the study were 448 samples from patients receiving anticoagulants (oral anticoagulants, 228; heparin, 166; heparin and warfarin, 130) and 351 samples from patients requiring coagulation screens (PT, APTT, TCT, Fib). Tests were done in parallel with tilt-tube manual techniques and the results correlated. The correlation coefficients were PT, 0.99; TCT, 0.72; APTT, 0.96; Fib, 0.97. Discrepancies were analyzed and were due to hypofibrinogenemia and hyperlipidemia. The poorer correlation coefficient of TCT was attributable both to lower reproducibility of the manual test and the effect of dysfibrinogenemia or FDPs in liver disease. In no case was an abnormality or diagnosis missed using the centrifugal analyzer. In several cases the increased sensitivity of the analyzer improved the detection of the lupus anticoagulant. The use of automation was accompanied by a major reduction in workload and reagent costs. The machine has been used to assay a wide range of coagulation tests by clot based and chromogenic substrate methods. In conclusion, a programmed centrifugal analyzer is a safe, efficient, and flexible way of automating routine coagulation tests. It widens the reportoire of tests performed in the Hemostasis laboratory by using a machine capable of being used in other areas of pathology. PMID- 3348170 TI - Heparin cofactor II assay. Elimination of heparin and antithrombin-III effects. AB - Functional assays for heparin cofactor II (HC-II) are based on the inactivation of thrombin by HC-II in the presence of dermatan sulfate (DS). Residual thrombin is measured in a chromogenic assay. Interference by the antithrombin-III (AT III)/heparin complex, which also rapidly inactivates thrombin, must be eliminated from the HC-II test system. Commercial DS is contaminated with heparin, while plasma specimens to be tested contain AT-III. After NaNO2/acetic acid treatment of DS (to inactivate heparin), there was enough residual heparin to cause AT-III interference. Treatment of plasma with commercially available anti-AT-III antiserum largely, but not completely, removed AT-III interference from the HC-II assay. With commercially available reagents, both NaNO2/acetic acid treatment of DS and anti-AT-III treatment of plasma were needed to eliminate heparin/AT-III interference. Protamine sulfate inactivated DS as well as heparin and could not be used to reduce AT-III/heparin interference with the HC-II assay. PMID- 3348171 TI - The prognostic value of DNA ploidy combined with histologic substaging for incidental carcinoma of the prostate gland. AB - Although current methods of histologic substaging for incidental prostatic carcinoma are useful, they offer only general indications of potential tumor behavior. To further define the biologic tendencies of stage A cancers, an examination was made of the role of DNA ploidy combined with histologic staging in archival material selected to achieve both a representative sample and long term follow-up. With histology alone, 36% of stage A2 cancers and 9% of A1 neoplasms were progressive. Adding DNA flow cytometry to histology resulted in a significant improvement in the capacity of pathologic evaluation to predict outcome. Progression occurred in 67% of aneuploid stage A2 prostate cancers and in none of the nonaneuploid stage A1 tumors. Despite current limitations in the interpretation of DNA histograms from archival tissue, flow cytometry has significant potential in the pathologic evaluation of incidental prostatic carcinomas. PMID- 3348172 TI - An analysis of the transfusion medicine content of the test of the National Board of Medical Examiners. AB - A two-year (1984-1985) review of 3,764 questions appearing on Part I and Part II of the National Board of Medical Examiners (NBME) indicated 140 (4%) were transfusion medicine (TM)-related. Fewer questions on TM appeared on Part II than Part I (45 vs. 95, P less than 0.001). Unexpectedly, the lowest proportion of questions (excluding psychiatry) in the Part II examination was in the surgery section. Part I NBME appears to adequately reflect and assess the TM content of the medical school curricula, but the number and distribution of questions in Part II of the NBME does not reflect recent changes in the clinical transfusion medicine curricula of many United States medical schools. PMID- 3348173 TI - Thawing of fresh-frozen plasma at 45 degrees C versus 37 degrees C. Comparison using satellite packs of the same donor units. AB - Packs of fresh-frozen plasma (FFP) from the same donor units were thawed at 37 degrees C and at 45 degrees C in order to determine the suitability of the higher temperature for thawing FFP. Measurements of prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and Factor VIII activity showed no significant differences between the temperatures. Thawing time at 45 degrees C was approximately half that at 37 degrees C. The protocol for manipulation and inspection of the FFP was an important determinant of the thawing time, but did not appear to affect coagulation. FFP can safely be thawed in a 45 degrees C water bath if it is removed before thawing is complete. PMID- 3348174 TI - Direct wet mounts versus concentration for routine parasitological examination: are both necessary? AB - The authors evaluated the usefulness of direct wet mount microscopic examination of stool samples for routine parasitologic diagnosis compared with formalin-ethyl acetate concentration detection. Over a three-year period, there were no instances in which an intestinal parasite was detected only by the direct wet mount examination. Elimination of routine direct wet mount examinations can reduce laboratory cost and save significant technologist time without decreasing the sensitivity of microscopic examinations for common parasitic agents. PMID- 3348175 TI - Predictive value of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of strongyloidiasis. AB - Strongyloides stercoralis is an opportunistic parasite of increasing importance in immunocompromised hosts. Current parasitologic methods for diagnosis are unsatisfactory, and the serologic screening of candidates for immunosuppression and other individuals at risk might prevent fatal disseminated infections. The predictive value of an enzyme-linked immunosorbent assay (ELISA) using S. stercoralis antigens has been evaluated on 268 infected patients, 571 noninfected controls, and 78 individuals with other parasitic infections. A positive test was accurate in predicting the presence of S. stercoralis in 97% of the cases, while a negative test was associated with absence of infection in 95% of the patients. Possible cross-reactivity occurred in some patients with Loa loa filariasis and Ascaris lumbricoides. The authors conclude that the ELISA is a reliable and cost effective method for the screening of patients at risk, and its results can be used to determine the appropriateness of more in-depth parasitologic evaluation. PMID- 3348176 TI - Fenoprofen-induced immune hemolysis. Difficulties in diagnosis and complications in compatibility testing. AB - A 70-year-old man developed severe immune intravascular hemolysis and renal failure following ingestion of fenoprofen, a nonsteroidal, anti-inflammatory drug. The patient's red blood cells were sensitized with both IgG and C3d. The serum reacted with normal red blood cells in the presence and absence of the drug. Addition of albumin to the serum inhibited the reactivity with both neat and drug-treated serum. These atypical serologic findings for drug-related immune hemolytic anemia were explained by (1) the measurement of fenoprofen by high performance liquid chromatography (HPLC) in the neat serum; and (2) solid-phase adsorption studies showing that albumin can bind drug, leading to the disappearance of agglutination when albumin is added. This case demonstrates the utility of drug levels and adsorption techniques to confirm the diagnosis of drug induced immune hemolytic anemia despite the anomalous serologic results which obscured the diagnosis and management of the patient. PMID- 3348177 TI - S-100 immunoreactivity in normal human peripheral blood lymphocytes. PMID- 3348178 TI - Frequent urinary tract infections in girls. PMID- 3348179 TI - The emperor is indeed stark raving naked. PMID- 3348180 TI - Changing needles when drawing up vaccines and medications. PMID- 3348182 TI - Bicycle helmet education project. PMID- 3348181 TI - Nutritional rickets. PMID- 3348184 TI - Still's murmur. PMID- 3348183 TI - Parent errors following physician instruction. PMID- 3348185 TI - More thoughts about retirement. PMID- 3348186 TI - Sexual precocity in girls. An association with sexual abuse? AB - The development of secondary sexual characteristics before 8 years of age in girls is uncommon and little is known of its epidemiology. In a retrospective study of a population of 105 girls 10 years old and younger who were victims of confirmed or suspected sexual abuse, we found a one in 15 prevalence of early development (before 8 years of age) of one or more secondary sexual characteristics. We speculate on possible associations between early development of secondary sexual characteristics and sexual abuse. The data suggest that further research explore this possible association. PMID- 3348188 TI - Kawasaki syndrome clusters in Harris County, Texas, and eastern North Carolina. A high endemic rate and a new environmental risk factor. AB - Sixty-one cases of Kawasaki syndrome (KS) occurred in Harris County, Texas, during the three-year period from January 1982 through December 1984. Fifty-five (90%) of these 61 patients were under 5 years old, for an annual endemic rate in children under 5 years old of 9.1 cases per 100,000 per year. To our knowledge this is the highest endemic rate reported to date in the continental United States. Between Aug 26 and Sept 19, 1984, seven children with KS were hospitalized in Harris County. The seven children were between 5 months and 5 years old. The number of cases in this cluster was unusual for late summer, which is generally a low-incidence season for KS in Harris County. More important, a case-control study of these children revealed that they resided significantly closer to a bayou or drainage ditch than did randomly selected matched control subjects. A similar association with drainage ditches or creeks was observed in a subsequent cluster of 13 cases of KS in seven eastern North Carolina counties. To our knowledge, this is the first report of a possible association between KS and residing near water. PMID- 3348187 TI - Racial differences in neonatal mortality. What causes of death explain the gap? AB - To examine further the differences in birth-weight-specific neonatal mortality rates between ethnic groups, we studied causes of death for infants of white, black, United States-born Hispanic, and Mexican-born Hispanic women using linked California birth-death records from 1981 to 1983. Black infants of low birth weight had considerably lower neonatal mortality rates from respiratory distress syndrome and congenital abnormalities. In the normal birth-weight category, however, black neonatal mortality rates for most conditions were higher than those for whites. The greatest differences between Mexican-born Hispanic and white neonatal mortality rates were seen for other respiratory conditions and trauma/hypoxia/asphyxia. These differences were most marked in the 1500- to 2499 g and greater than or equal to 2500-g birth-weight categories. Attempts to lower the neonatal mortality rate for black infants of normal birth weight may require providers to focus on both broad preventive measures and improved perinatal management. In contrast, improvements in perinatal management among Mexican-born Hispanics may produce improvement in the neonatal mortality rate for this group. PMID- 3348189 TI - Human milk supplementation. Delivery of energy, calcium, phosphorus, magnesium, copper, and zinc. AB - Human milk when fed to preterm infants is frequently supplemented with human milk fortifiers that provide an additional source of protein, energy, and minerals. Human milk that was provided by the mother of a preterm infant, and that was supplemented with commercially available human milk fortifiers, was assessed under simulated syringe-pump and bolus feeding circumstances for the delivery of energy, calcium, phosphorus, copper, magnesium, and zinc to an infant. In general, the nutrients were not completely delivered with syringe-pump feedings, with the greatest losses occurring in the concentrations of calcium and phosphorus. The losses were more pronounced with the use of a powdered fortifier than with the use of a liquid fortifier. Little or no change in the concentrations of the various nutrients were observed with simulated bolus feeding. We suggest that human milk fortified with supplements be fed with care to assure complete delivery of the nutrients and that infants receiving such feedings be monitored to assure adequate nutritional status. PMID- 3348190 TI - The preservation of excellence in a hostile health care environment. PMID- 3348191 TI - The symptom index: a clinically important parameter of ambulatory 24-hour esophageal pH monitoring. AB - Ambulatory 24-h esophageal pH monitoring is an accurate quantitative test of gastroesophageal reflux (GER). However, it does not answer the question: are the patients' symptoms due to GER? We developed a numerical scale to quantify the percent association between symptoms and pH less than 4--the symptom index (SI). In 100 consecutive patients with heartburn or chest pain, the SI for the chief complaint was either high (greater than 75%) or low (less than 25%) in 77% of cases. A similar bimodal distribution was seen when heartburn or chest pain symptoms were individually evaluated. There was a good association between high SI and the presence of GER (97.5%), as well as low SI and a normal 24-h pH study (81.1%). Endoscopy was normal in 89.5% of patients with low SI, but patients with high SI had esophagitis in only 69.7% of cases. The Bernstein test showed a poor association with the SI. Therefore, the SI gives clinically relevant information regarding the role of acid reflux and patient's symptoms. We believe this simple calculated index should be included in the analysis of 24-h esophageal pH studies. PMID- 3348192 TI - Gastrointestinal symptoms, motility, and transit after the Roux-en-Y operation. AB - Roux-en-Y patients have symptoms that vary from almost none to inability to tolerate oral feedings. This study was designed to determine whether there is a relationship between a patient's symptoms and the function of the gastric remnant or the Roux-limb. Gastric remnant and Roux-limb emptying were studied in eight patients with technetium-99m-labeled oatmeal and Roux-limb motor activity was measured with a water-perfused manometry system. We found that gastric emptying was rarely significantly slowed, but emptying of the Roux-limb was delayed in several patients. We also found that there was a rough correlation between the patient's symptoms and the degree of abnormal motility found in the Roux-limb. There is no known reason for these abnormalities in Roux-limb function in some patients after a Roux-en-Y, but our finding of worse abnormalities in those who had multiple previous gastric surgeries suggests that the symptoms and dysfunction may be related to the number of surgeries, as well as to the type of surgery. PMID- 3348194 TI - Will the new special requirements for fellowship training in gastroenterology impact negatively on community hospitals? PMID- 3348193 TI - Smoking and inflammatory bowel disease in families. AB - Smoking habits of inflammatory bowel disease (IBD) patients were compared with family members with IBD to determine the effects of cigarette smoking on the development of either ulcerative colitis or Crohn's disease. In a previous study of patients randomly selected from the University of Chicago IBD Registry, 40 patients with IBD were identified as having a confirmed IBD family history. Thirty-one of those probands and relatives were contacted and included in this study. Of the 36 patients in the study with Crohn's disease, 78% were former or current smokers, whereas only 27% of the 26 patients with ulcerative colitis were former or current smokers. Eighty-three percent of all those who had ever smoked, started before the onset of symptoms of their disease. There were high concordance rates for type of IBD (81%) and for smoking habits (65%, when a history of smoking was compared with a history of never having smoked) among the matched pairs. The concordance rates were not significantly different from each other, but the magnitude of concordance of each suggests that both smoking habits and consanguinity may be important factors in the pathogenesis of this disease. PMID- 3348195 TI - Adenomyoma of the common bile duct. AB - We report an unusual case of biliary obstruction secondary to adenomyoma of the common bile duct. Adenomyomas are benign tumors, found infrequently in the biliary tree. Clinical presentation, biochemical, radiographic, and endoscopic investigations do not distinguish adenomyomas from malignant or other lesions; diagnosis requires histological examination. The natural history and optimal treatment of these tumors have not been established. PMID- 3348196 TI - Esophagocolonic stricture with proximal fistulae treated by balloon dilation. AB - Anastomotic fistulae are uncommon complications after gastrointestinal surgery. We describe an unusual case of an esophagocolonic stricture after colonic interposition for benign disease complicated by proximal esophageal fistulae successfully treated with balloon dilation. PMID- 3348197 TI - A malignant gastric leiomyoblastoma presenting as an infected pseudocyst of the pancreas. AB - Malignant gastric leiomyoblastoma (epithelioid leiomyosarcoma) is an uncommon smooth muscle neoplasm which is generally slow growing but capable of attaining large size. When these tumors project extrinsically from their site of origin in the gastric wall, they present diagnostic difficulty to the clinician and radiologist. This case report documents a highly unusual example of such a tumor which presented as an infected pancreatic pseudocyst and produced symptoms related to inferior vena caval compression. PMID- 3348198 TI - Stercoral perforation of the colon: report of a new location. AB - Stercoral perforations of the colon unassociated with obstructive lesions are rarely reported. With the exception of one case report which described a stercoral perforation of the cecum, all the reported perforations occurred at the sigmoid or rectosigmoid colon. This report describes a new location of perforation which hitherto has not been reported. PMID- 3348199 TI - Anal metastasis from colorectal carcinoma. PMID- 3348200 TI - Perforation of a metastatic lung adenocarcinoma of the jejunum. PMID- 3348201 TI - Prognostic factors in chronic myelodysplastic syndromes: a multivariate analysis in 107 cases. AB - A retrospective multivariate analysis of 37 clinical, biochemical, and hematological data was performed in 107 cases of primary myelodysplastic syndromes (MDS) in order to recognize their prognostic significance. The most important individual variables, isolated in a previous univariate analysis, were placed in a multiple regression modeling procedure to identify major significant prognostic factors. Multivariate analysis tends to identify prognostic variables containing significant independent predictive information. Characteristics were examined on both continuous and binary bases. The FAB classification was the first parameter entered in regression equations on both models, followed by platelet count, hemoglobin level, and circulating erythroblasts in the binary model, and by hemoglobin level, systemic symptoms, platelet count, age, and dyserythropoiesis in the continuous model. Our analysis confirms FAB classification as the main prognostic factor in MDS, supports the previously noted predictive value of platelet count, hemoglobin level, and age, and recognises the importance of circulating erythroblasts, systemic symptoms, and dyserythropoiesis as prognostic characteristics in MDS. PMID- 3348203 TI - Mean platelet volume is increased in hyperthyroidism. AB - In 28 unselected patients with hyperthyroidism, platelet count, platelet hematocrit, mean platelet volume, and platelet distribution width were measured at the time of presentation and again when the patients were euthyroid. On return to the euthyroid state, there were highly significant falls in the mean values of the mean platelet volume (16% decline, P less than 0.001) and the platelet hematocrit (16% decline, P less than 0.001) and a slight but highly significant increase in the mean value of the platelet distribution width (2% increase, P less than 0.01). A decline in mean platelet volume was observed in 24 of 28 patients (86%); three patients showed no change. There was no significant change in the mean value of the platelet count. The observed effects of thyrotoxicosis on platelets appeared to be largely independent of the well-known effects on erythrocytes and white blood cells. An increase in mean platelet volume is a regular feature of hyperthyroidism that has not previously been described. PMID- 3348202 TI - Unbalanced translocation (1;7) in childhood myelodysplasia. AB - We have identified an unusual pediatric patient among twelve patients with myelodysplasia and an unbalanced translocation involving chromosomes 1 and 7: -7, +der(1)t(1;7)(p11;p11). This 16-year-old male patient developed myelodysplasia and evolving acute leukemia, which were preceded by a 7-year history of marrow hypoplasia. The remaining patients were adults with clinical and hematologic findings similar to other reported cases with this chromosomal abnormality. The late appearance of this unbalanced clonal abnormality in this patient with marrow hypoplasia documents the importance of close cytogenetic follow-up of all patients with suspected bone marrow injury. PMID- 3348204 TI - Hemoglobin Pasadena: identification of the gene mutant by DNA analysis using synthetic DNA probes. AB - Hemoglobin Pasadena [beta 75(E19)Leu----Arg] was found in a boy who had an acute episode of anemia and rapid splenic enlargement. His father was the only other member of a large family with this hemoglobinopathy. We have used gene mapping techniques for direct identification of the beta-globin gene mutation. To correlate the DNA findings with the structural identification of this variant, we have also performed globin chain separation and analysis of the tryptic peptides using high performance liquid chromatography and secondary ion mass spectral analysis. PMID- 3348205 TI - Cerebral thrombosis in a newborn with a congenital deficiency of antithrombin III. AB - An Israeli Arab family with type I antithrombin III (AT-III) deficiency with several affected symptomatic members in three generations is reported. The propositus presented with deep vein thrombosis and pulmonary emboli associated with gestation. The propositus infant presented at the age of 2 weeks with superior sagittal and rectus sinus thrombosis. Hereditary AT-III deficiency should be considered in infants with cerebral thrombosis, especially if they have a family history of thromboembolism. The role of prophylactic therapy by AT-III concentrates in these infants should be further assessed. PMID- 3348206 TI - Thrombotic thrombocytopenic purpura in human immunodeficiency (HIV)-seropositive males. AB - Two male patients with thrombotic thrombocytopenic purpura (TTP) were found to have antibodies to the human immunodeficiency virus (HIV). In one patient, platelet-associated antibody levels were measured serially and were found to be initially elevated, but the levels decreased with initiation of successful therapy. The simultaneous occurrence of these two conditions in two of three patients admitted for TTP within the previous 2 years at this institution suggests an association between the two diseases. The precise nature of this association remains speculative inasmuch as the pathogenesis of TTP remains uncertain. PMID- 3348208 TI - Congenital Pelger-Huet anomaly in triplets. AB - Congenital Pelger-Huet anomaly is an autosomal dominant disorder characterized by incomplete nuclear segmentation of granulocytes. The morphology of these mature but hyposegmented granulocytes may be confused with that of immature granulocytes (bands), thereby suggesting bacterial infection. We report the first known case of triplets with this condition, and emphasize the need to identify accurately this normal variant. PMID- 3348207 TI - Elevated erythrocyte adenosine deaminase activity in a patient with primary acquired sideroblastic anemia. AB - We report a case of primary acquired sideroblastic anemia (PASA) associated with elevated erythrocyte adenosine deaminase (ADA) activity. The patient was an 85 year-old Japanese male. Analysis of the peripheral blood revealed pancytopenia, and the bone marrow findings showed marked ringed sideroblasts and chromosomal deletion (46XY, 11q-). The erythrocyte ADA activity was 17 times higher than that of normal control, the leukocyte ADA activity was within the normal range, and the plasma ADA activity was 2 times higher than the normal mean. The adenine nucleotides in the patient's erythrocytes were within normal range. According to starch gel electrophoresis, ADA isozyme of the patient was ADA 1. Western blotting showed an increased amount of ADA protein in the patient's erythrocytes. Southern blotting revealed no gene amplification or large structural change. Dot blot analysis of the reticulocyte mRNA showed no increase in the amount of ADA mRNA in the patient's reticulocytes compared with those of reticulocyte-rich controls. We considered that the mechanism of elevated ADA activity in this acquired defect was similar to that found in hereditary hemolytic anemia associated with ADA overproduction. PMID- 3348209 TI - Leukocytosis due to adrenal metastases from malignant melanoma: reversal after bilateral adrenalectomy with long-term survival. AB - Leukocytosis has been noted in association with many non-hematologic malignancies in the absence of concurrent infection or metastatic involvement of bone marrow. We report a case of sustained, neutrophilic leukocytosis in a patient with disseminated malignant melanoma which reversed after bilateral adrenalectomy for adrenal metastases. PMID- 3348210 TI - Thrombocytosis and spontaneous abortion. PMID- 3348211 TI - Gonadal dimorphism explained as a dosage effect of a locus on the sex chromosomes, the gonad-differentiation locus (GDL). AB - In human somatic cells bearing two X chromosomes, one X is genetically inactivated throughout most of its length, whereas in cells with one X and one Y both sex chromosomes are active (with the exception of the constitutive heterochromatin of the Y that is inert). The vast base of information concerning normal and abnormal human sexual development that has accumulated since the advent of human cytogenetics 3 decades ago can be integrated by the following hypothesis: Homologous gonad-differentiation loci (GDLs) exist on the X and Y. The GDLs are strictly sex-linked; that is, normally they do not recombine during spermatogenesis, so that considerable divergence in DNA sequence doubtless has occurred between the locus on the X and the locus on the Y. The abundance of their evolutionarily conserved product--a substance still to be identified- determines the path of differentiation that the indifferent gonadal anlage of the early embryo will take: if only one GDL is transcribed, the case when two X chromosomes are present, ovary will develop; if two GDLs are transcribed, the case when a Y is present along with an X, testis will develop. By implication, facultative X inactivation is an integral and essential component of the system adopted in mammalian evolution for accomplishing gonadal--viz., sexual- dimorphism. PMID- 3348213 TI - Genetic studies of human apolipoproteins. IV. Structural heterogeneity of apolipoprotein H (beta 2-glycoprotein I). AB - Human beta 2-glycoprotein I has recently been identified as a component of several human plasma lipoprotein fractions and therefore termed as apolipoprotein H. Its metabolic function in lipid metabolism is not known with certainty, though it may be involved in very-low-density-lipoprotein metabolism. Previously, inherited quantitative variation in beta 2-glycoprotein I has been suggested in man. In this investigation, we document the evidence of genetically determined structural polymorphism of apolipoprotein H or beta 2-glycoprotein I by using thin-layer polyacrylamide isoelectric focusing gels followed by immunological identification by double antibody staining. The apolipoprotein H structural locus is characterized by the occurrence of three common alleles in U.S. whites and blacks. The frequency distributions of the three alleles designated APO H1, APO H2, and APO H3 are .059, .882, and .059 in whites and .017, .902, and .068 in blacks, respectively. In addition, the gene product of a fourth allele, APO H4, has been observed at polymorphic frequency in black individuals and may represent a black marker variant. Family data confirm the hypothesis of four alleles at a single APO H gene locus with an autosomal codominant pattern of inheritance. PMID- 3348212 TI - Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen. AB - Type VI collagen is a heterotrimer composed of three polypeptide chains, alpha 1(VI), alpha 2(VI), and alpha 3(VI). By immunological screening of an expression cDNA library, human cDNAs specific for each chain were isolated and characterized. Major mRNA species encoding these chains have a size of 4.2 kb (alpha 1), 3.5 kb (alpha 2), and 8.5 kb (alpha 3). The cDNA clones were also used to map the genes on human chromosomes by somatic cell hybrid analysis and in situ hybridization. The alpha 1 (VI) and alpha 2(VI) collagen genes were both located on chromosome 21, in band q223. This represents a third example of a possible physical proximity of two collagen loci. The alpha 3(VI) collagen gene was localized to chromosome 2, in the region 2q37. The alpha 3(VI) collagen gene is the fifth extracellular matrix gene to be localized to 2q, as four other extracellular matrix genes--i.e., the alpha 1(III) and alpha 2(V) collagen genes, the elastin gene, and the fibronectin gene--have been previously mapped to the distal region of the long arm of chromosome 2. PMID- 3348215 TI - Multifactorial analysis of family data ascertained through truncation: a comparative evaluation of two methods of statistical inference. AB - When family data are ascertained through single selection based on truncation, a prevailing method of analysis is to condition the likelihood function on the proband's actual phenotypic value. An alternative method conditions the likelihood function on the event that the proband's measurement lies in the truncation region. Both methods are contrasted here by using Monte Carlo simulations; identical sets of data were analyzed using both methods. The results suggest that, under either method, (1) parameter estimates are nearly unbiased and (2) likelihood-ratio tests of null hypotheses are approximately distributed as chi 2. However, conditioning on the proband's actual phenotypic value yields considerably less efficient estimates and reduced power for hypothesis tests. A corresponding result also holds under complete ascertainment. It is argued, therefore, that whenever sufficient information is available on the nature of truncation, the alternative approach should be used. PMID- 3348214 TI - Ultraviolet light-induced chromosomal aberrations in cultured cells from Cockayne syndrome and complementation group C xeroderma pigmentosum patients: lack of correlation with cancer susceptibility. AB - Both Cockayne syndrome (CS) and xeroderma pigmentosum (XP) are inherited diseases with defective repair of damage induced in DNA by UV. Patients with XP, but not those with CS, have an increased susceptibility to formation of sunlight-induced skin tumors. We determined the frequency of UV-induced chromosomal aberrations in cultured lymphoblastoid cell lines from five CS patients and three complementation-group-C XP patients to determine whether such aberrations were abnormally increased only in the XP cells. We found that CS cells had the same abnormally increased number of induced aberrations as the XP cells, indicating that the number of UV-induced aberrations in XP group C cells does not account for the susceptibility of these XP patients to sunlight-induced skin cancer. PMID- 3348216 TI - Glucose 6-phosphate dehydrogenase deficiency and incidence of hematologic malignancy. AB - We have evaluated the hypothesis of a negative association between glucose 6 phosphate dehydrogenase (G6PD) deficiency and cancer in a cohort of 481 Sardinian males with hematological malignancies. The frequency of G6PD deficiency in the patients was not different from the incidence in a group of 16,219 controls. The same conclusion resulted from the comparison of the frequency of expression of the GdB gene in 23 heterozygous women having a clonal hematologic disease and a control group of 37 healthy heterozygotes. Therefore at present there is no evidence that G6PD deficiency has a protective effect against development of hematologic neoplasms. PMID- 3348217 TI - Regional assignment of six polymorphic DNA sequences on chromosome 21 by in situ hybridization to normal and rearranged chromosomes. AB - We have assigned six polymorphic DNA segments to chromosomal subregions and have established the physical order of these sequences on the long arm of chromosome 21 by in situ hybridization of cloned probes to normal metaphase chromosomes and chromosomes 21 from individuals with three different structural rearrangements: an interstitial deletion, a ring chromosome, and a reciprocal translocation involving four different breakpoints in band 21q22. Segments D21S1 and D21S11 map to region 21q11.2----q21, D21S8 to 21q21.1----q22.11, and D21S54 to 21q21.3--- q22.11; D21S23 and D21S25 are both in the terminal subband 21q22.3, but they are separated by a chromosomal breakpoint in a ring 21 chromosome, a finding that places D21S23 proximal to D21S25. The physical map order D21S1/D21S11-D21S8 D21S54-D21S23-D21S25 agrees with the linkage map, but genetic distances are disproportionately larger toward the distal end of 21q. PMID- 3348218 TI - Introduction and expression of the human Bs-globin gene in transgenic mice. AB - Owing to the episodic and unpredictable nature of the sickling crisis, many aspects of the disease sickle cell anemia have resisted in vivo analysis. The lack of an animal model has hindered the pathophysiological investigation of this disease, as well as deterred the development of pharmacological therapies. The transgenic mouse system offers a new means for creating animals that make a specified mutant gene product, and we have used this system to create a series of mice that contain the human beta s-globin gene. These animals express this gene in the appropriate tissues and at the same point in development as the adult mouse globin genes are expressed. We have crossed the human beta s-containing transgenic mice with a beta-thalassemic mouse line and examined the hemoglobins produced by these mice. Their red cells contain 10% mouse alpha/human beta s hybrid hemoglobin, which partially corrects the thalassemic phenotype of the homozygous beta-thalassemic animals. Though the red cells do not sickle, other properties of the human beta s gene in these mice indicate the potential for the eventual development of a transgenic animal model for sickle cell anemia. PMID- 3348219 TI - Attitudes of genetic counselors: a multinational survey. AB - Of 1,053 medical geneticists in 18 nations 677 (64%) returned questionnaires on their views on the importance of seven goals of genetic counseling, the appropriateness of five directive/nondirective approaches to counseling, and their choices of action in four situations involving directive/nondirective counseling. The majority (92%-94%) regarded nondirective approaches as appropriate; their views on both goals and approaches were similar to those reported in an earlier survey of 205 genetic counselors in the United States. In clinical situations involving presentation of reproductive options to carriers of disorders not diagnosable prenatally, 74%-85% would present contraception, sterilization, taking one's chances, artificial insemination donor (AID), or adoption as options even if not asked; 66% would present in vitro fertilization (IVF) with a donor egg; and 46% (67% in the United States) would present surrogate motherhood. In regard to three situations involving fetuses with low burden disorders (Turner syndrome, XYY, and a possible small neural tube defect), 84%-88% would counsel nondirectively. Stepwise logistic regression analyses on professional and personal background variables showed that gender was related, cross-nationally, to self-reported directiveness in counseling, with men more likely than women to regard directive approaches as appropriate, more likely to give advice about fetuses with low-burden disorders, and more likely to present either IVF with donor egg or surrogate motherhood as options. Social and ethical implications of this widespread acceptance of nondirective counseling are discussed. PMID- 3348221 TI - Career patterns of pioneer clinical pharmacists. AB - The career paths of some early clinical pharmacists from their first positions during the years 1965-1974 to their current positions were studied. In August 1985 a group of pharmacists was surveyed to determine (1) the extent to which they had maintained a clinical practice (defined as direct patient contact, including evaluating and planning drug regimens), (2) the number of job-function changes, and (3) the degree of the pharmacists' commitment to public service, as measured by Hall's Belief in Public Service and Allport-Vernon-Lindzey Personality Values. The response rate for the 337 questionnaires was 73.5%. The average age of the group was 40 years; 83% were men, and 79% possessed Doctor of Pharmacy degrees. The respondents had changed job functions an average of 2.1 +/- 1.5 times over the last 13 years since the highest professional degree. The percentage in the job functions of hospital pharmacist and pharmacy faculty declined over time while those in hospital pharmacy administration, academic administration, and the pharmaceutical industry increased. Clinical-practice activity declined over time, with a twofold net increase in those reporting no direct patient-care responsibilities. Male respondents with fewer years after their highest professional degree, a greater belief in public service, higher theoretical values, and no residency experience were more likely to be currently involved in direct patient care than others. Although attrition among pioneer clinical pharmacists is not excessive for those who began their careers with a relatively small percentage of their time devoted to clinical practice, most pharmacists who began with substantial clinical commitments have reduced or eliminated clinical activities over time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348220 TI - Genetic polymorphism of human serum ribonuclease I (RNase I). AB - One of the human urinary ribonucleases (RNases) was isolated and purified to homogeneity (SDS-PAGE) by means of a series of column chromatographies. The enzyme, designated RNase 1, is a glycoprotein with a molecular weight of approximately 16,000. Rabbit antibody to the purified RNase 1 reacted with human urine and sera, as well as with the purified RNase 1. The genetic polymorphism of serum RNase 1 was studied by polyacrylamide gel isoelectric focusing (IEF-PAGE) in a pH range of 5-8, followed by immunoblotting with antisera specific for RNase 1. Two common phenotypes, RNASE1 1 and RNASE1 1-2, were easily recognized. The homogeneous phenotype, RNASE1 1, consisted of four major bands with different pI values, and the heterogeneous phenotype, RNASE1 1-2, was presumed to represent a mixture of each of the homogeneous phenotypes 1 and 2; however, the other homogeneous phenotype, RNASE1 2, was not detected in our samples. Family studies are in agreement with an autosomal codominant transmission of the two alleles. Population studies indicate that the frequencies of the RNASE 1 and RNASE1 2 alleles are .988 and .012, respectively. PMID- 3348222 TI - Economics of providing antineoplastic drugs in a manufacturer-mixed bulk package. AB - The cost impact of converting from a hospital-mixed (HM) system for preparing antineoplastic-drug doses to a manufacturer-mixed bulk package (MMBP) system in a 565-bed comprehensive cancer center is analyzed. The cost per dose for nine antineoplastic agents--bleomycin, cisplatin, cyclophosphamide, doxorubicin, fluorouracil, methotrexate, mitomycin, vinblastine, and vincristine--was assessed for each system. The average dose for each drug was determined by reviewing nearly 2200 physician orders collected over nine days. Cost per dose was calculated by allocating the costs associated with the production of multiple dose containers and withdrawal of a single dose. A time-and-motion study using standard industrial engineering methodology measured labor times for all tasks associated with the production of drug doses. Calculated costs included direct labor, drug expense, supply expense, drug waste, waste removal, overhead, management labor, and inventory reduction. Operating costs (labor, supplies, overhead, and waste and waste removal) were reduced by an average of 26% per dose for all drugs, using the MMBP system. This institution produces a high volume of antineoplastic admixtures; thus, the impact on operating costs is likely to be different in other institutions. The total measured operating and drug acquisition costs decreased for three drugs, marginally increased for five drugs, and increased substantially for one drug. Based on this institution's use of the nine antineoplastic agents, the total first-year savings from conversion from the HM system to the MMBP system would be $31,219, including a one-time inventory reduction of $94,621. However, in subsequent years, use of the MMBP system would result in increased costs of $63,402.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348223 TI - Effects of simulated facility-design changes on outpatient pharmacy efficiency. AB - The potential effects of using the Baker drug counter or the Systamodule pharmacy fixture, or both, on the efficiency of the current outpatient pharmacy system at the National Institutes of Health were evaluated by computer simulation. It was hypothesized that the use of these two devices would reduce (1) the prescription filling time (RxFT) and (2) the distance traveled (DT) by pharmacists in filling individual prescriptions. The sample used was 20% of two weeks' prescriptions, randomly selected. All theoretical estimations of RxFT were done by a computer program; DT was calculated based on measurements from the architect's schematic drawings. The effect of the application of the Baker drug counter alone, the Systamodule pharmacy fixture alone, and the Baker drug counter in combination with the Systamodule pharmacy fixture was to reduce the prescription-filling time by 0.123, 0.159, and 0.280 minutes per prescription, respectively. The average DT per prescription, 102 feet, was identical in the current NIH pharmacy and with use of the Baker counter. It was reduced by 86.3% (to 14 feet) with use of the Systamodule feature, both alone and in combination with the Baker counter. The use of the Baker drug counter and the Systamodule together promises improved efficiency of the prescription dispensing operation. PMID- 3348224 TI - Multidisciplinary cost-containment program promoting oral metronidazole for treatment of antibiotic-associated colitis. AB - A multidisciplinary cost-containment program for promoting oral metronidazole in place of oral vancomycin as initial therapy of antibiotic-associated colitis (AAC) is described. The pharmacy department and the division of infectious diseases implemented the program in two phases. In the first phase, a one-year retrospective drug-use review in patients with AAC treated with oral vancomycin was conducted to determine the average cost of therapy per treatment course. In the second phase, the use of oral metronidazole instead of oral vancomycin for initial treatment of AAC was promoted using inservice-education programs and distribution of pocket-size brochures containing AAC treatment guidelines to medical staff. The pharmacy and therapeutics committee supported the program by endorsing metronidazole as the drug of choice for AAC and by distributing follow up progress reports of the program to medical staff. Pharmacists on the nursing units were responsible for enforcing the program stipulations regarding vancomycin and metronidazole use and for collecting data on patient-specific drug use. Six months after implementation of the program, the average cost of drug therapy for AAC had decreased by 89%, from $343.24 per patient to $37.50 per patient. The projected annual savings resulting from the program was $38,829.02. All prescribing physicians and dispensing pharmacists complied 100% with the program stipulations regarding drug use. The multidisciplinary program described here was successful in promoting the use of oral metronidazole for initial therapy of AAC. PMID- 3348225 TI - Effect of data collection method on results of serum digoxin concentration audit. AB - The appropriateness of serum digoxin concentration (SDC) orders was evaluated with respect to indication for use, sampling time, and action taken by physicians when the reported SDC was out of the normal therapeutic range; the effect of the two data-collection methods used (retrospective and concurrent audits) on the results was studied. Criteria for the appropriate use of SDCs were approved by the medical staff through the pharmacy and therapeutics committee. Patients on adult medicine services were entered into the study as daily SDC determinations were reported by the clinical laboratory. Most of the SDCs were evaluated using approved criteria by primary pharmacist clinicians who were concurrently monitoring drug therapy and participating with the treatment team. A retrospective audit of the same patients was conducted, using only chart review. A total of 134 SDCs involving 78 patients were evaluated. Concurrent-audit results indicated that 18.7% of the SDCs were ordered without an appropriate indication, 16.4% were sampled incorrectly with respect to proper timing, and 8.2% did not result in dosage adjustments when indicated. With respect to appropriate sampling time and overall use of SDCs, significantly more SDCs met the standards under concurrent audit than under retrospective audit. The retrospective chart review method of auditing may not detect as much pertinent information as is desirable. PMID- 3348226 TI - Delivery of paraldehyde in 5% dextrose and 0.9% sodium chloride injections through polyvinyl chloride i.v. sets and burettes. AB - The delivery of paraldehyde in 5% dextrose injection and 0.9% sodium chloride injection was studied, and the potential interaction between paraldehyde and plastic i.v. containers and sets was evaluated. Paraldehyde was mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags to form a 4% solution. The bags were fitted with standard i.v. administration sets or burettes with administration sets. The solutions were allowed to drip through the i.v. sets for six hours at room temperature. Samples were taken from the i.v. bag or burette and from the distal end of the i.v. sets at zero, two, four, and six hours. Paraldehyde concentrations were measured using a stability-indicating gas chromatographic method, and the presence of plasticizers was detected by a scanning ultraviolet spectrophotometer. The cumulative amount of paraldehyde delivered at the end of the administration set at six hours was 84% for 5% dextrose solutions in burettes, and 89% or 90% for all other solutions and i.v. sets. An ultraviolet-light-absorbing substance appeared in some of the samples, although a relationship between the presence of this substance and type of solution, time of sampling, or site of sample did not emerge. Particulate matter appeared after two hours in all burettes. Approximately 10%-16% of paraldehyde in 5% dextrose or 0.9% sodium chloride injection is lost when delivered from PVC i.v. bags through standard i.v. administration sets and burettes over a six-hour period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348228 TI - Compatibility of verapamil hydrochloride with penicillin admixtures during simulated Y-site injection. AB - The compatibility of verapamil hydrochloride during simulated Y-site injection with i.v. admixtures containing 11 different penicillins was studied. Admixtures of penicillin G potassium (62.5 mg/mL), nafcillin sodium (40 mg/mL), oxacillin sodium (40 mg/mL), ampicillin sodium (40 mg/mL), carbenicillin disodium (40 mg/mL), methicillin sodium (40 mg/mL), ticarcillin sodium (40 mg/mL), azlocillin sodium (40 mg/mL), mezlocillin sodium (40 mg/mL), piperacillin sodium (40 mg/mL), and amdinocillin (20 mg/mL) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Verapamil hydrochloride injection 4 mL (10 mg) was then added to each admixture, and the admixtures were examined macroscopically and microscopically for precipitate immediately and at 15 minutes and 24 hours after mixing. To simulate Y-site injection of verapamil, verapamil hydrochloride injection 1 mL (2.5 mg) was added to 1 mL of each penicillin admixture in a test tube. For admixtures in which precipitates formed, the pH was recorded before and after verapamil was added to the admixtures. Loss of verapamil hydrochloride when mixed with the penicillin admixtures was determined using reverse-phase high-performance liquid chromatography. Addition of verapamil hydrochloride to admixtures containing nafcillin sodium, oxacillin sodium, ampicillin sodium, and mezlocillin sodium resulted in substantial loss of verapamil hydrochloride. The results for the Y-site injection study showed visible precipitation with the same penicillin admixtures. Because a precipitate formed when verapamil hydrochloride was added to nafcillin sodium, oxacillin sodium, ampicillin sodium, or mezlocillin sodium in the diluents studied, we recommended that verapamil hydrochloride be administered separately or that the i.v. tubing be flushed thoroughly before and after this drug is administered through a Y-injection site with these penicillin admixtures. PMID- 3348227 TI - Sweetener content of common pediatric oral liquid medications. AB - The types and concentrations of sweeteners in common prescription liquid and chewable medications for pediatric use were determined by manufacturer survey. Oral-liquid and chewable antibiotic, antifungal, bronchodilator, antihistamine, anticonvulsant, and miscellaneous products were identified. The manufactures were asked by telephone the type and amount of sweeteners in their products. Two follow-up letters requested confirmation of the sweetener contents; manufacturers' approval for publication of the information was also requested by mail. Sweetener information on 160 preparations was obtained. For antibiotics such as ampicillin, amoxicillin, erythromycin ethylsuccinate, and penicillin VK, products from different manufacturers had a wide range of sucrose concentration (18%-80%). Only four antibiotic preparations were sucrose free. The bronchodilators and antihistamines contained either sucrose, sorbitol, or saccharin. The anticonvulsants contained 0%-60% sucrose. Health-care practitioners who prescribe or dispense oral liquid or chewable prescription drug products should know that products in a given category can vary in type and amount of sweetener. PMID- 3348230 TI - The new nursing shortage. PMID- 3348229 TI - Principles and methods of managerial cost-accounting systems. AB - An introduction to cost-accounting systems for pharmacy managers is provided; terms are defined and examples of specific applications are given. Cost accounting systems determine, record, and report the resources consumed in providing services. An effective cost-accounting system must provide the information needed for both internal and external reports. In accounting terms, cost is the value given up to secure an asset. In determining how volumes of activity affect costs, fixed costs and variable costs are calculated; applications include pricing strategies, cost determinations, and break-even analysis. Also discussed are the concepts of direct and indirect costs, opportunity costs, and incremental and sunk costs. For most pharmacy department services, process costing, an accounting of intermediate outputs and homogeneous units, is used; in determining the full cost of providing a product or service (e.g., patient stay), job-order costing is used. Development of work-performance standards is necessary for monitoring productivity and determining product costs. In allocating pharmacy department costs, a ratio of costs to charges can be used; this method is convenient, but microcosting (specific identification of the costs of products) is more accurate. Pharmacy managers can use cost-accounting systems to evaluate the pharmacy's strategies, policies, and services and to improve budgets and reports. PMID- 3348232 TI - Poison prevention programs should be ongoing. PMID- 3348231 TI - Pharmacist liability for injury resulting from use of neomycin irrigation. PMID- 3348233 TI - Incorrect instructions for use of metered-dose inhalers. PMID- 3348234 TI - Opportunities for pharmacists in hospice organizations. PMID- 3348236 TI - Managing costs: a health-care imperative. PMID- 3348235 TI - Dear Mr. Ziegler. PMID- 3348237 TI - Nonsteroidal anti-inflammatory drug-induced gastrointestinal damage. Current insights into patient management. Proceedings of a symposium. June 13, 1987, Washington, D.C. PMID- 3348238 TI - Ulcer complications and nonsteroidal anti-inflammatory drugs. AB - Rates of ulcer perforation, hospital admission, and death are usually regarded as the best available measures of the frequency of severe peptic ulcer disease. Overall admission rates have tended to decline, which almost certainly reflects the widespread adoption of effective outpatient therapy. The overall incidence of ulcer perforation and death may also have fallen. However, at least in Europe, and in the United Kingdom in particular, there may be differences between the young and the elderly; rates of perforation and death in the young appear to be declining, whereas they are rising or static in the elderly. Although there are various interpretations for these changing patterns, data for the United Kingdom suggest that during the last 15 to 20 years some unidentified factor or factors began to influence the rates of severe peptic ulcer disease among the elderly. At least part of this change may reflect increasingly frequent prescribing of nonsteroidal anti-inflammatory drugs (NSAIDs). In the United Kingdom, most adverse drug reactions attributable to NSAIDs are gastrointestinal and are usually serious. Bleeding and perforation are common, may occur in the absence of warning symptoms, and are associated with a high mortality rate. In some countries, other factors, including smoking and diet, may be equally important. It is difficult to determine the relative contribution of each factor, though the widespread perception that the gastrointestinal tolerance of NSAIDs is poor, particularly in the elderly, may be well founded. About half the prescriptions for non-aspirin NSAIDs in the United Kingdom are for patients over 60 years of age. About one quarter of all cases of upper gastrointestinal bleeding in the elderly are likely caused by NSAIDs and are associated with a death rate of 10 percent or possibly higher. Although the absolute risk of a serious gastrointestinal complication may be low, perhaps one in several thousand NSAID prescriptions, the total burden of disease is high because of the multimillion NSAID prescriptions issued yearly. PMID- 3348239 TI - Direct medical costs of disease and gastrointestinal side effects during treatment for arthritis. AB - We conducted a study to determine the costs of caring for patients with arthritis. Data were obtained from the Medicaid Management Information System (MMIS) of Washington, DC. A retrospective analysis was undertaken of all direct medical costs related to individual Medicaid recipients who obtained treatment for arthritis. First, all data were adjusted for patient compliance with nonsteroidal anti-inflammatory drugs (NSAIDs). Second, we determined the actual expenditure of treating arthritis. Last, the medical costs of treating adverse gastrointestinal side effects were examined. There was a linear relationship between compliance and pharmaceutical dose schedule per diem. Treatment costs per quarter were $145; 54 percent of the cost was for NSAIDs with the remainder equally divided between physician and hospital costs. Approximately 25 percent of the population experienced NSAID-related gastrointestinal side effects that required further medical care. The per-quarter mean cost of treating these adverse gastrointestinal drug reactions was $66 per person, which added nearly 46 percent to the per-quarter mean cost of treatment. The total cost of treating patients with arthritis therefore averaged $211 per quarter. Nearly one third of overall cost went to provide medical care to the 25 percent of the population who experienced adverse reactions, and slightly more than two thirds went towards treating the disease itself. Overall costs of treating adverse drug reactions were accounted for by pharmaceuticals (about 42 percent), usually the histamine (H2)-receptor antagonist cimetidine, rare but expensive inpatient hospital care (about 38 percent) and physician visits (about 20 percent). PMID- 3348240 TI - Damage and protection of the human gastric mucosa. A multiparameter assessment. AB - Studies in animals and humans have indicated that endogenous prostaglandins as well as synthetic prostaglandin analogues can prevent gastric mucosal damage induced by various agents. Methods were developed to assess induced damage and the effects of potentially protective agents (synthetic prostaglandin analogues and the histamine [H2]-receptor antagonist cimetidine) on the human gastric mucosa by measuring ion fluxes and transmucosal potential difference, as well as by observations with gastrointestinal endoscopy. Commonly ingested agents, such as aspirin, 1,300 mg, and 20 percent ethanol increased hydrogen ion and sodium ion fluxes, decreased potential difference, and caused gross mucosal damage, as observed by endoscopy. Conversely, acetaminophen, 2,600 mg, and 10 percent ethanol did not have any significant effects. Hyperosmolar solutions (1,800 and 3,600 mOsm/kg) also produced acute damage. Sodium taurocholate (10 mmol/liter) when instilled into the stomach, either at pH 1.1 or 7.0, produced both functional and structural damage. When given as a single dose, neither 15(R)15 methyl PGE2 nor the synthetic PGE1 analogue, misoprostol, prevented mucosal damage induced by aspirin and taurocholate (pH 1.1), respectively. Cimetidine, 400 mg orally, however, did reduce aspirin-induced mucosal damage, and this effect was independent of gastric acid inhibition. PMID- 3348241 TI - Cardiopulmonary and gas exchange responses to acute strenuous exercise at 1,270 meters in sickle cell trait. AB - The impact of strenuous exercise and environmental hypoxia on sickle cell trait (SCT) remains controversial. To determine if these factors induce cardiopulmonary and gas exchange abnormalities in SCT, healthy, young black male volunteers, 25 with SCT (HbAS) and 16 control subjects (HbAA), were evaluated during incremental and steady-state exercise tests using a cycle ergometer at 1,270 meters and 24 degrees C. Peak incremental exercise values for power (242 +/- 7 versus 253 +/- 10 watts), oxygen consumption (3.08 +/- 0.1 versus 3.26 +/- 0.14 liters/minute), heart rate (188 +/- 2 versus 189 +/- 3 beats/minute), minute ventilation (129 +/- 4.6 versus 144 +/- 7.7 liters/minute), oxygen pulse (16.4 +/- 0.5 versus 17.3 +/- 0.8 ml/beat), and respiratory exchange ratio (1.31 +/- 0.01 versus 1.33 +/- 0.02) revealed no significant differences (p less than 0.05) between the SCT and control groups, respectively. Peak incremental exercise values for arterial oxygen tension (82 +/- 1.7 versus 82 +/- 2.2 mm Hg), arterial carbon dioxide tension (32 +/- 0.7 versus 31 +/- 0.9 mm Hg), and alveolar-arterial oxygen pressure differences (19 +/- 1.4 versus 21 +/- 1.9 mm Hg) were similar for the SCT and control groups, respectively. Steady-state exercise results corroborate incremental exercise findings. It is concluded that cardiopulmonary and gas exchange responses to a brief period of strenuous exercise performed at low altitude at 24 degrees C in a well-characterized SCT sample of recruits were within normal limits and comparable to those of a carefully selected control sample. PMID- 3348242 TI - Echocardiographic recognition of pulmonary arterial disease and determination of its cause. AB - Echocardiography provided the initial diagnosis of significant pulmonary hypertension, unrelated to left heart pathologic conditions, in 10 patients: four with acute pulmonary embolism; five with chronic pulmonary hypertension, primary in three patients and secondary to tumor emboli in the other two patients; and one with Eisenmenger's syndrome due to previously unsuspected atrial septal defects. Referral diagnoses were pericardial disease in five patients (including three with suspected tamponade), and right ventricular infarction versus pericarditis, atrial septal defect, dyspnea, inferoposterior infarction (by electrocardiography), and Ebstein's malformation in one patient each. The echocardiographic diagnoses were confirmed by lung scan (ventilation/perfusion mismatches were interpreted as high probability for pulmonary emboli in all four patients considered to have acute pulmonary emboli by echocardiographic study), pulmonary angiography (one patient), cardiac catheterization (four patients), and autopsy (three patients). No patient had evident aortic or mitral valvular, myocardial, or other left heart pathologic condition. In acute pulmonary embolism, mean right ventricular diameter was increased at 4.2 cm (range 3.2 to 6 cm) and right ventricular wall thickness was normal (mean 4.5 mm, range 3 to 5 mm). Moderate or marked right ventricular hypokinesis was noted in two patients each. Doppler examination, performed in three patients, revealed tricuspid regurgitation in all, with an increased flow velocity suggestive of mild to moderate systolic pulmonary hypertension (right ventricular minus right atrial pressures of 28 to 36 mm Hg). Patients with chronic pulmonary hypertension also had right ventricular dilatation (mean 4.4 cm diameter, range 3 to 5.4 cm) and hypokinesis (marked in four and moderate in one patient), but wall thickness was increased in all (mean of 9 mm, range 6 to 14 mm) and the flow velocities in the tricuspid regurgitant jets, detected by Doppler in all patients, suggested higher right ventricular minus right atrial pressures of 44 to 104 mm Hg (mean 64 mm Hg). The single patient with Eisenmenger's syndrome had right ventricular dilatation (3.2 cm), hypertrophy (10 mm), and hypokinesis (mild). Only the patient with Eisenmenger's syndrome had Doppler or contrast echocardiographic evidence for an intracardiac or extracardiac shunt. In the absence of left heart pathologic conditions, right ventricular dilatation and hypokinesis strongly suggest pulmonary arterial or primary right ventricular disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3348244 TI - Reduced specificity of the clonidine suppression test in patients with normal plasma catecholamine levels. AB - Although originally devised to discriminate between patients with pheochromocytoma and those with elevated plasma catecholamine levels for other reasons, the clonidine suppression test has recently been used in patients with normal resting catecholamine levels. Upon review of 49 patients evaluated for pheochromocytoma, 26 had elevated plasma norepinephrine levels and underwent clonidine suppression testing. Only one of 13 patients with sustained elevated norepinephrine levels before clonidine administration had a false-positive clonidine test result, in contrast to five of 13 patients whose pre-clonidine norepinephrine levels had decreased into the normal range. This difference was statistically significant (by chi-square) at p less than 0.05. Clonidine suppression testing for pheochromocytoma should be performed only in patients with elevated catecholamine levels, because it carries a higher false-positive rate in patients with normal resting norepinephrine levels; a more accurate diagnosis may be made in such patients using glucagon stimulation tests. PMID- 3348243 TI - Hemodynamic responses to noninvasive external cardiac pacing. AB - Although improvements in noninvasive external cardiac pacing have led to a technique with reliable electrical capture and reduced patient discomfort, hemodynamic responses to this pacing mode have not been described previously. Accordingly, this technique was applied to 16 patients with a clinical diagnosis of angina pectoris undergoing cardiac catheterization. Three patients had normal coronary arteries, whereas the remaining 13 had significant coronary artery disease. All patients had noninvasive pacing at increasing heart rates to 85 percent of age-predicted maximal heart rate. At maximal pacing, all patients demonstrated a rise in atrial, pulmonary artery, and mean aortic pressures. Cardiac index remained unchanged, reflecting parallel increases in arteriovenous oxygen difference and oxygen consumption. One minute after cessation of pacing, pulmonary artery pressure and oxygen consumption remained elevated, whereas arteriovenous oxygen difference returned to baseline with a subsequent rise in cardiac index. Angina occurred in eight patients with coronary artery disease at peak pacing and was accompanied by a rise in left ventricular end-diastolic pressure after pacing. In eight patients without pacing-induced angina, including the three patients with normal coronary arteries, there was no significant change in left ventricular end-diastolic pressure after pacing. It is concluded that noninvasive external cardiac pacing produces a rise in both right and left heart filling pressures and in oxygen consumption that persist after pacing, and may provoke angina and hemodynamic abnormalities consistent with myocardial ischemia. This mode of pacing appears hemodynamically safe with maintenance of cardiac index and aortic pressure at 85 percent of maximal age-predicted heart rate. PMID- 3348245 TI - Central nervous system metastases from non-Hodgkin's lymphoma: treatment and prophylaxis. AB - Central nervous system (CNS) lymphoma was identified in 96 patients treated for non-Hodgkin's lymphoma at Memorial Sloan-Kettering Cancer Center between 1975 and 1981. During the same period, 68 other patients with non-Hodgkin's lymphoma but no CNS disease received prophylactic CNS chemotherapy. In the 156 total patients, the lymphomas were diffuse in 96 percent, and 67 percent were stage IV at diagnosis. CNS involvement was present at initial diagnosis in 27 percent, at relapse in 26 percent, and during the course of progressive systemic disease in 47 percent. CNS involvement was asymptomatic in 10 percent. Cytologic study of the cerebrospinal fluid was the most sensitive and specific laboratory test, but often (22 percent) more than one lumbar puncture was required to identify malignant cells. CNS lymphoma was treated in 85 patients, 46 by intracerebroventricular cannulae; 81 percent improved. Although median survival after the diagnosis of CNS disease was four months, there were seven long-term disease-free survivors and the CNS disease contributed to death in only 14 percent. In 52 percent of treated patients, there was no CNS lymphoma at autopsy. CNS prophylaxis was with methotrexate or cytosine arabinoside, usually by lumbar puncture; an intraventricular cannula was used in seven patients. Although this group of high-risk patients with non-Hodgkin's lymphoma had a high systemic response rate and the median projected survival was greater than five years, CNS lymphoma developed in eight patients (12 percent). In five, CNS lymphoma occurred as an apparently isolated relapse site. The role of CNS chemoprophylaxis in high risk patients with non-Hodgkin's lymphoma is still uncertain. PMID- 3348246 TI - Sudden death in sickle trait. PMID- 3348247 TI - Cardiovascular collapse and death in a 55-year-old woman with cervical cancer. PMID- 3348248 TI - Fraud, distortion, delusion, and consensus: the problems of human and natural deception in epidemiologic science. PMID- 3348249 TI - Science in medicine: too much or too little and too limited in scope? AB - Contrary to the common assertion that there is too much science in medicine, it is precisely the application of the natural sciences in the clinic that has enhanced the diagnostic and therapeutic powers of the physician. Much of the criticism of science in medicine mistakes the technology made possible by science, and the way that technology is employed, for science itself. What has hampered progress is too narrow a view of the sciences relevant to medicine. The concepts and methods of the social sciences must be integrated into medical education if physicians are to be enabled to respond effectively to illness as a human experience. Nonetheless, without major changes in the social context of medical practice, efforts to improve performance through curriculum reform will be futile. PMID- 3348250 TI - On the importance of retaining a feeling of sensitivity and wonder during years of intensive medical training. PMID- 3348251 TI - Hereditary spherocytosis in the elderly. AB - Five patients with hereditary spherocytosis diagnosed in their seventh to ninth decades of life are presented. These patients are remarkable for absent or mild clinical manifestations of disease. Splenectomy is the recommended treatment for hereditary spherocytosis to avoid the complications of aplastic or hemolytic crisis. When the diagnosis is made in the elderly, the treatment of choice may be careful observation with folic acid supplementation rather than splenectomy. This recommendation is based on the incidence of complications of splenectomy in the elderly in comparison to the severity and incidence of complications from the disease itself. PMID- 3348252 TI - Two apparent glucose-6-phosphate dehydrogenase variants in normal XY males: G6PD Alabama. AB - A six-year-old black boy who had transient hemolysis after a viral infection was found to have mildly decreased red cell glucose-6-phosphate dehydrogenase (G6PD) activity (1.25 IU/g hemoglobin). Two G6PD bands, both slightly faster than normal G6PD B, were seen on electrophoresis in both the propositus as well as in his maternal grandfather. This is an unexpected finding, since the G6PD gene is located on the long arm of the X chromosome that is subject to X-chromosome inactivation, and available evidence indicates that it is present as a single functional copy in the human genome. The obvious possibility of duplication of the X chromosome was eliminated by cytogenetic analysis with G-banding. G6PD duplication is unlikely, since peripheral blood granulocytes, platelets, and lymphocytes; cultured skin and bone marrow fibroblasts; and Epstein-Barr virus stimulated lymphocytes yielded only a single electrophoretic band with mobility identical to the slower band seen in crude red blood cell hemolysate. Study of partially purified red blood cell hemolysate G6PD also yielded a single band with identical mobility. Kinetic studies of the enzyme in the propositus and in three generations of his family identified a unique, previously unpublished G6PD mutant that is herein designated G6PD Alabama. Red blood cells were separated by density gradient into a reticulocyte-enriched, an intermediate, and a dense, older portion. Two distinct enzyme bands were identified on electrophoresis of hemolysate from the reticulocyte-enriched portion, but not from the other two portions. It is postulated that two transcriptional products of the mutant G6PD gene exist; one with a short half-life and detectable only in young red blood cells, and another with a longer half-life present in all cells. The existence of two distinct mutant genes in the genome or a unique post-translational form of the mutant G6PD detected only in reticulocytes cannot be excluded. PMID- 3348254 TI - X-linked lymphoproliferative syndrome. Identification of a large family in Switzerland. AB - Observation of a patient with acquired hypogammaglobulinemia associated with a mononucleosis syndrome led to the identification of one of the largest families affected by the X-linked lymphoproliferative (XLP) syndrome in the world. It is the first such family identified in Switzerland and the largest in Europe. At least nine male subjects over two generations presented phenotypic expressions consistent with the XLP syndrome. Study of the pedigree extending over seven generations suggests that the mutation occurred in the proband's great grandmother. In the next generation, a second mutation of the X chromosome in one branch of the family resulted in expression of hemophilia A in the children. This remarkably large family, comprising six living obligate female carriers, displays a wide spectrum of the XLP syndrome and offers valuable information for future genetic linkage studies and for genetic counseling. PMID- 3348253 TI - POEMS syndrome presenting as systemic sclerosis. Clinical and pathologic study of a case with microangiopathic glomerular lesions. AB - A rare form of plasma cell dyscrasia characterized by the various association of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes has been termed POEMS syndrome. The pathogenesis of the multisystemic features of this syndrome remains unclear. Herein is reported a case of POEMS syndrome with striking clinical similarities with scleroderma, and microangiopathic glomerular lesions, as well as diffuse perivascular non-amyloid deposits, which could explain certain features of the syndrome, including peripheral nerve demyelination. It is proposed that a pathogenic role might be played by a non-immunoglobulin vasculotoxic component. PMID- 3348255 TI - Recurrent fever of unknown origin, coma, and meningismus due to a leaking craniopharyngioma. AB - A cyclic leaking craniopharyngioma was found to be the source of recurrent fevers, meningismus, and coma. A sterile persistent neutrophilic pleocytosis with normal glucose and protein was the only clue in an extensive workup. Three head computed tomographic scans, including double contrast with 5-mm cuts, failed to locate the large suprasellar cyst outlined finally by head computed tomographic scan with metrizamide. A handful of case reports exist about leaking central nervous system cysts, but their presentation tended to be different: increased protein, lymphocytosis, and positive cranial imaging. It is believed this is a unique case that adds to the spectrum of chronic neutrophilic meningitis. PMID- 3348256 TI - Wound zygomycosis (mucormycosis) in otherwise healthy adults. AB - Two previously healthy men sustained trauma that caused extensive soft tissue damage together with soil contamination. Within three days, rapidly advancing necrosis was observed at the wound margins. Histologic examination revealed the presence of non-septate branching hyphae characteristic of Mucorales within tissues and in the lumen of blood vessels. In one case, the disease was unrecognized until widespread dissemination had taken place, and the patient died; in the other, a cure resulted from aggressive medical and surgical management. Infections due to Mucorales generally occur in immune-compromised hosts. In cases of extensive trauma, inoculation of devitalized tissues with soil may initiate infection by zygomycetes, even in persons whose immunologic status appears to be normal. PMID- 3348257 TI - Termination of ventricular tachycardia by chest wall stimulation during DDD pacing. A report of two cases. AB - This report describes the use of chest wall stimulation (CWS) for the termination of ventricular tachycardia in two patients with dual chamber pulse generators functioning in the DDD mode. Rapid CWS induced burst ventricular pacing when CWS was selectively sensed by the atrial channel, whereupon the pulse generator triggered its ventricular output. In this way, by programming the pulse generators to the maximum upper rate, this CWS technique produced burst ventricular pacing at a rate of 175 to 180/minute that successfully terminated ventricular tachycardia in both patients. The same CWS technique also initiated ventricular tachycardia by burst ventricular pacing. This CWS technique may be useful for the termination of relatively slow ventricular tachycardia in patients with DDD pulse generators when the maximum rate of ventricular pacing cannot be otherwise increased. PMID- 3348259 TI - Clinical assessment of extracellular fluid volume in hyponatremia. PMID- 3348258 TI - Vancomycin-induced interstitial nephritis. PMID- 3348261 TI - On the positioning of a nasogastric tube. PMID- 3348260 TI - Diabetes mellitus in elderly patients. PMID- 3348262 TI - Acute dystonic reaction to cocaine. PMID- 3348264 TI - Lung bullae with air-fluid levels. PMID- 3348263 TI - Urinary digoxin-like immunoreactive substance in pregnancy. PMID- 3348265 TI - Chloroquine neuromyotoxicity. PMID- 3348266 TI - Toxins, test tubes, and tampons. PMID- 3348267 TI - Serious Pseudomonas infections associated with endoscopic retrograde cholangiopancreatography. AB - After observing a single case of Pseudomonas aeruginosa bacteremia following endoscopic retrograde cholangiopancreatography (ERCP), six other P. aeruginosa infections that were temporally related to ERCP were retrospectively found over one year (August 1985 through July 1986) at LDS Hospital. In all seven patients, infection developed within five days after an ERCP. Five patients had bacteremia and two had cholangitis. All five of the Pseudomonas isolates available for testing were serotype 010. Cultures from the ERCP endoscope and several other endoscopes also yielded P. aeruginosa serotype 10, as did environmental cultures from equipment used to clean endoscopes. Among 167 ERCPs performed during the outbreak period, no other patient acquired P. aeruginosa infection. Each of the patients in the outbreak received the first scheduled ERCP of the day. The mean duration between the cleaning of the ERCP endoscope and its subsequent use was significantly longer in cases than in matched controls, a factor that may have permitted contaminating organisms to achieve high inocula in the inadequately cleaned endoscope. Epidemic control measures included improved disinfection of endoscopes, ongoing surveillance, and appropriate antimicrobial prophylaxis. This experience suggests that exogenous infection with Pseudomonas is associated with ERCP, that protracted and insidious outbreaks may occur, and that the occurrence of even a single case of Pseudomonas infection after ERCP should stimulate an epidemiologic investigation. PMID- 3348268 TI - Treatment of pneumonia in patients at risk of infection with gram-negative bacilli. AB - Patients with a history of chronic debilitating disease due to a variety of causes are known to be at risk for infection with coliform gram-negative bacilli when they present with community-acquired pneumonia. Empiric treatment with broad spectrum parenteral antibiotics is often begun in such patients pending the result of blood and other cultures. The optimal duration of broad-spectrum empiric therapy in such patients when cultures fail to reveal a specific pathogen is unknown. Review was made of the charts of 131 patients with community-acquired pneumonia admitted to the hospital and treated with broad-spectrum parenteral antibiotics in whom a specific pathogen was never isolated. Overall, 89 percent of these patients were cured without complication or relapse. Patients receiving broad-spectrum therapy for four days or less due to rapid clinical improvement had a successful outcome in 95 percent of cases. It is concluded that broad spectrum parenteral antibiotic therapy can safely be abbreviated provided response to therapy is prompt. PMID- 3348270 TI - Hospital survey of antimicrobial prophylaxis to prevent endocarditis in patients with prosthetic heart valves. AB - The American Heart Association (AHA) has published guidelines for use of prophylactic antibiotics to prevent bacterial endocarditis, but few data are available about physician compliance with these guidelines. A retrospective review was conducted of the use of prophylactic antibiotics in patients with prosthetic heart valves who were undergoing diagnostic or operative procedures or heart catheterization at three hospitals. Compliance with AHA recommendations was only 30 percent (14 of 46) for procedures considered high risk for patients with prosthetic heart valves. Six (23 percent) of 26 patients who underwent right or left heart catheterization received prophylactic antibiotics (not recommended by AHA). Antibiotics were given to 42 (74 percent) of 57 patients who underwent surgical procedures considered at low risk of bacteremia, but only 33 (58 percent) received antibiotics that cover organisms commonly present at the site of the procedure. The results indicate that clinicians frequently do not administer prophylactic antibiotics in patients with prosthetic heart valves who are undergoing invasive procedures or do not follow published AHA guidelines when antibiotics are administered. PMID- 3348269 TI - Endocrine disorders in men infected with human immunodeficiency virus. AB - Gonadal, adrenal, and thyroid functions were evaluated in 70 men seropositive for human immunodeficiency virus (HIV) infection, clinically categorized as asymptomatic (n = 19), AIDS-related complex (ARC) (n = 9), or acquired immunodeficiency syndrome (AIDS) (n = 42). Twenty of 40 men (50 percent) with AIDS were hypogonadal. Mean serum testosterone concentrations in both ARC (292 +/ 70 ng/dl) and AIDS (401 +/- 30 ng/dl) men were significantly less than in asymptomatic (567 +/- 49 ng/dl) or normal men (608 +/- 121 ng/dl). Of these hypogonadal men, 18 of 24 (75 percent) had hypogonadotropic hypogonadism. Seven of eight hypogonadal men (88 percent) had a normal gonadotropin response to gonadotropin-releasing hormone administration. Hypogonadism correlated with lymphocyte depletion and weight loss. Adrenal cortisol reserve, evaluated by adrenocorticotropin stimulation, was normal in 36 of 39 patients (92 percent) with AIDS. Indices of thyroid function were normal with the exception of one ARC man with a low free thyroxine index. In conclusion, hypogonadism is common in men with HIV infection and may be the first or most sensitive endocrine abnormality. PMID- 3348271 TI - Tuberculosis of the sacroiliac joint: clinical features, outcome, and evaluation of closed needle biopsy in 11 consecutive cases. AB - Sacroiliac joint (SIJ) involvement has been reported in up to 9.7 percent of patients with skeletal tuberculosis. Lack of awareness of this now uncommon form of infection often leads to diagnostic delay and increased morbidity. Eleven consecutive cases of SIJ tuberculosis are reported; clinical and radiologic features, diagnosis, treatment, and outcome are discussed. Buttock pain was the presenting complaint in all patients. However, radicular pain in the lower back (seven patients) or lower limb (10 patients) was common and in one patient precipitated an unnecessary surgical intervention. SIJ tuberculosis is frequently an isolated phenomenon. Therefore, direct sampling of the SIJ is necessary to establish the diagnosis. The recently described technique of closed needle biopsy of the SIJ was employed in all 11 patients and established the diagnosis in nine of the 11. PMID- 3348272 TI - Toxic shock syndrome associated with use of a nasal tampon. AB - Toxic shock syndrome has been noted to occur with nasal surgery, both with and without packing. A new synthetic sponge, described as a nasal tampon, has become available for use as packing after surgery. Herein is reported the first case of toxic shock syndrome associated with the use of this nasal tampon. PMID- 3348273 TI - Hemorrhagic cystitis due to herpes simplex virus as a marker of disseminated herpes infection. AB - Herpetic cystitis has rarely been reported. Herein are described two immunocompromised female patients with genital or buttock herpetic lesions in whom hemorrhagic cystitis due to herpes simplex virus type 2 developed in the setting of disseminated herpetic infection. Both patients had indwelling Foley catheters. Urinary tract instrumentation may cause local or widespread dissemination of genital herpes in immunocompromised patients. PMID- 3348274 TI - Disseminated Mycobacterium haemophilum infection in two patients with the acquired immunodeficiency syndrome. AB - In two patients with the acquired immunodeficiency syndrome (AIDS), multiple erythematous cutaneous lesions developed, revealing acid-fast organisms on Fite's stain. Initial culture results on the first patient were negative; however, repeat cultures on hemin-enriched media were positive for Mycobacterium haemophilum. Despite antimycobacterial therapy, lesions persisted until the patients' death. M. haemophilum should be a diagnostic consideration when smears of peripheral (especially skin) lesions from AIDS patients show acid-fast organisms. Cultures in such patients should be done with iron hemin- or ferric ammonium citrate-enriched media. PMID- 3348276 TI - Haitians can give blood. PMID- 3348277 TI - A simulated disaster drill. PMID- 3348275 TI - The spiral of technology. PMID- 3348278 TI - The primacy of caring. PMID- 3348279 TI - Stopcock contamination. PMID- 3348280 TI - Hypertensive crisis in L & D. PMID- 3348281 TI - Managing leaking gastrostomy sites. PMID- 3348283 TI - The pathological "cue" wave. PMID- 3348282 TI - Nursing diagnosis: translate please! PMID- 3348285 TI - New age nursing. PMID- 3348284 TI - Managing chemotherapy-induced emesis. PMID- 3348286 TI - Ordered to care. PMID- 3348287 TI - Perils of home care. PMID- 3348288 TI - Patients need skilled and highly trained RNs. PMID- 3348290 TI - Your first job. Great news or giant nightmare? PMID- 3348289 TI - National hearings on infant mortality. PMID- 3348291 TI - Big differences in little people. PMID- 3348292 TI - Home oxygen. Transtracheal and other options. PMID- 3348293 TI - On being gay, single, and bereaved. PMID- 3348294 TI - Drug dependency in hospital patients. PMID- 3348295 TI - Write on. PMID- 3348296 TI - Tuberculosis in hospital employees. PMID- 3348297 TI - New York Metro jobfocus. The Big Apple shines for nurses. PMID- 3348298 TI - Megamother and me. PMID- 3348299 TI - A legacy from Vietnam. PMID- 3348300 TI - The role of Chlamydia trachomatis in Bartholin's gland abscess. AB - Chlamydia trachomatis is becoming increasingly known for its ability to cause severe injury to the female genital tract. Little investigation has been done in its role in diseases of Bartholin's glands. We present what we believe to be the first case report of an abscess of a Bartholin's gland in which Chlamydia trachomatis was a major pathogen. This communication also review the literature concerning the microbiology of Bartholin's gland abscess. PMID- 3348301 TI - Cesarean section and perinatal outcome: response from the House of Horne. AB - A direct comparison between Parkland Memorial Hospital in Dallas, Texas, and the National Maternity Hospital in Dublin, Ireland, on the basis of limited numbers taken from one year only (1983) led to the conclusion that the liberal use of cesarean section in Dallas was associated with a sevenfold decrease in intrapartum fetal deaths and a twofold decrease in neonatal seizures. However, when the scope of the survey is extended to include the year before (1982) and the year after (1984), a different picture emerges. During this extended period there were almost four times as many cesarean sections performed in Dallas with no significant difference in overall perinatal mortality, while for two of three years the incidence of neonatal seizures was twice as high in Dallas when compared with Dublin. The fact that high cesarean rates continue to rely on evidence of such a tenuous nature must remain a matter of concern. PMID- 3348302 TI - Clinical indications for pulmonary artery catheterization in the patient with severe preeclampsia. AB - The obstetric literature reflects an increased interest in invasive hemodynamic monitoring during the past decade. While much of this interest has focused on research applications, the patient with severe preeclampsia may benefit clinically from pulmonary artery catheterization under several circumstances. These conditions include severe hypertension unresponsive to conventional antihypertensive therapy, pulmonary edema, persistent oliguria unresponsive to fluid challenge, and in induction of conduction anesthesia in select patients. Theoretical and clinical evidence to support this contention is presented. PMID- 3348303 TI - Combination of surgical excision and carbon dioxide laser vaporization for multifocal vulvar intraepithelial neoplasia. AB - Ten patients with multifocal grade 3 vulvar intraepithelial neoplasia were treated by a combination of surgical excision and carbon dioxide laser vaporization of selected areas. The lesions treated by the laser were either on the clitoris or distal to the vulva. These areas could be functionally and anatomically deformed if surgically excised. Combining the carbon dioxide laser with surgery, however, resulted in a satisfactory cosmetic outcome and provided an adequate specimen for histopathologic diagnosis. PMID- 3348304 TI - Radical vulvectomy and "sneak" superficial inguinal lymphadenectomy with a single elliptic incision. AB - With a single elliptic radical vulvectomy incision, resection of the primary tumor and bilateral superficial inguinal lymphadenectomies were performed in 18 patients with invasive squamous cell carcinoma of the vulva. Twelve patients (67%) had no morbidity from the procedure, while five patients (28%) developed significant wound breakdown and one patient (5%) developed a groin hematoma. For select patients with invasive vulvar cancer, this modification of the standard "butterfly" incision offers an acceptable surgical approach to this disease, allowing removal of the primary lesion and adequate sampling of the groin lymphatics. Results of pathologic examinations allow selection of those patients requiring further therapy. PMID- 3348305 TI - Obstetric management and outcome related to maternal characteristics. AB - Presented are the results of a logit analysis of the variations in birth management and outcome, other than birth weight, associated with socioeconomic and physical maternal characteristics at a London teaching hospital. Previous studies have not attempted to discriminate rigorously between the effects of correlated explanatory variables. Logit analysis overcomes this problem by systematically measuring the independent effect of each maternal characteristic on each type of management and outcome, holding the effects of all other maternal characteristics constant. The results show that, in quantitative terms, parity and age have the greatest effects on both management and birth outcome. Stature is also an important factor for certain types of management, and ethnicity, occupation, and prenatal class attendance have some significant effects. In contrast to the literature on the determinants of birth weight, the smoking habit of the mother had no significant effect when all other factors were controlled for. PMID- 3348306 TI - Clinical features of small contraction wave recorded by an external tocodynamometer. AB - Clinical features of the small contraction wave recorded by a guardring tocodynamometer were examined retrospectively. This study included 578 patients and 6363 cardiotocographs ranging from 20 to 42 weeks of gestation. The small wave was observed in 7.5% of the cardiotocographs examined, and the rate of small wave appearance in each gestational week tended to decrease gradually as the pregnancy progressed. This was not observed after 41 weeks of gestation. The small wave-positive group had relatively poor obstetric parameters and fetal outcome, and the small wave was frequently observed in cases of effective beta 2 stimulant intravenous infusion for the treatment of preterm labor. These results suggest that the small wave represents some degree of contractility and is ominous in general; however, the appearance of the wave does not lead to a poor prognosis in preterm labor if large phasic contractions can be abolished by beta 2-stimulant treatment. PMID- 3348307 TI - The effect of pregnancy on metabolic responses during rest, immersion, and aerobic exercise in the water. AB - To examine the effects of advancing pregnancy on metabolic responses, 12 women, who were recruited early in pregnancy, were studied during 20 minutes of immersion in 30 degrees C water, followed by 20 minutes of exercise in the water (60% of predicted maximal capacity) and 20 minutes of lateral supine recovery. Each subject completed the trials during the fifteenth, twenty-fifth, and thirty fifth weeks of pregnancy, as well as a control period 8 to 10 weeks post partum. Resting oxygen uptake increased with advancing pregnancy. Resting oxygen uptake was higher in the water than on land but was not altered by pregnancy. Exercise oxygen uptakes were similar for all trials, but the work load required to elicit the VO2 decreased during the thirty-fifth week of pregnancy. Exercise heart rates followed the same pattern as oxygen uptake. Lactate concentrations declined with advancing pregnancy after exercise. Blood glucose levels were normal for pregnancy but declined slightly during exercise. Blood triglyceride levels were elevated with exercise, with a tendency to increase with advancing pregnancy. Resting plasma cortisol concentrations increased with pregnancy but remained lower during immersion and exercise. These results suggest that pregnancy significantly alters metabolic responses to exercise in the water. PMID- 3348308 TI - The effect of hepatitis B antigenemia on pregnancy outcome. AB - Sixty patients documented to have hepatitis B antigenemia during pregnancy were identified retrospectively and compared with an equal number of matched control patients. Maternal and newborn infant parameters were examined. No statistically significant differences were noted between the two groups, except for an increase in infant birth weight in the group showing antigen-positive test results, specifically in infants born to Oriental mothers. It is concluded that infants born to women testing positive for hepatitis B surface antigen represent normal infants eminently suitable for peripartal preventive immunotherapy. PMID- 3348309 TI - A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage. A review of 276 cases. AB - A total of 276 women underwent both panoramic hysteroscopy and dilatation and curettage. All of these patients underwent directed endometrial biopsies through the hysteroscope. Indications for operation included abnormal bleeding, postmenopausal bleeding, suspected leiomyoma with bleeding, follow-up for adenomatous hyperplasia, intrauterine contraceptive device with bleeding, retained products of conception, infertility with bleeding, abnormal hysterosalpingogram with bleeding, and abnormal endometrial cells on Papanicolaou smear. In 223 cases the results of hysteroscopy and curettage were in agreement. Hysteroscopy revealed more information than curettage in 44 patients, whereas curettage revealed more information than hysteroscopy in only nine patients. When the results of this study are combined with those of previous studies, there is little doubt that panoramic hysteroscopy is superior to curettage in making an accurate diagnosis of pathologic conditions in the uterine cavity. PMID- 3348310 TI - Infertility among daughters either exposed or not exposed to diethylstilbestrol. AB - Infertility was examined among 343 diethylstilbestrol-exposed and 303 unexposed daughters whose mothers participated in an evaluation of diethylstilbestrol use during pregnancy 35 years ago. Of the married individuals who were not using contraception and who were actively trying to conceive, a greater proportion of diethylstilbestrol-exposed women than unexposed subjects experienced primary infertility (33% versus 14%, p less than 0.001). Among those with primary infertility, abnormal hysterosalpingograms were observed in 46% of the diethylstilbestrol-exposed group and in none of the unexposed group (p less than 0.02), while tubal abnormalities were found in 42% of the exposed and in none of the unexposed (p = 0.02). First pregnancies were achieved by 40 (58%) women exposed to diethylstilbestrol and 18 (64%) unexposed subjects. Twenty-four (60%) of the exposed women and 15 (83%) of the unexposed individuals who conceived had a live-born infant who survived. The estimated cumulative rate of first pregnancy was 16% for the exposed group and 36% for the unexposed group at 12 months after the diagnosis of primary infertility (p less than 0.05). PMID- 3348311 TI - Noninvasive maternal stroke volume and cardiac output determinations by pulsed Doppler echocardiography. AB - Sixteen obstetric patients with pulmonary artery catheters were studied by two dimensional and pulsed Doppler echocardiography to compare prospectively pulsed Doppler-and thermodilution-derived estimations of left ventricular stroke volume and cardiac output. Systolic aortic flow velocity waveforms were obtained by pulsed Doppler ultrasound from the apical five-chamber echocardiographic window. Aortic diameters were obtained by two-dimensional echocardiography from the left parasternal long axis view. The mean (+/- SEM) aortic diameter averaged 2.1 +/- 0.1 cm, with a mean calculated aortic valve area of 3.6 +/- 0.2 cm2. The mean aortic flow velocity integral was 21.8 +/- 0.8 cm. This information was used to calculate aortic stroke volume and cardiac output. Thermodilution- and Doppler derived estimations for maternal stroke volume (r = 0.86) and cardiac output (r = 0.94) were significantly correlated when aortic diameter measurements based on a leading vessel edge method were used. Our findings verify the accuracy of an important noninvasive technique for quantitating maternal stroke volume and cardiac output by pulsed Doppler echocardiography. This methodology should provide an alternative approach to invasive monitoring in the study of normal and abnormal maternal circulatory hemodynamics. PMID- 3348312 TI - Hemodynamic profile of severe pregnancy-induced hypertension. AB - Cases of severe pregnancy-induced hypertension or eclampsia were studied in forty five women by catheterization of the right side of the heart to define the presenting hemodynamic profile associated with this disorder. These women could not be easily categorized into one specific hemodynamic pattern. Most patients had high-normal to elevated systemic vascular resistance indices (mean 2726 +/- 120 dynes.sec.cm-5.m2). The mean cardiac index was 4.14 +/- 0.13 L.min-1.m2. The severity of hypertension was largely attributable to a disproportionate rise in the systolic component (mean 193 +/- 3 mm Hg) compared with diastolic blood pressure (mean 110 +/- 3 mm Hg). Women with eclampsia had significantly lower arterial blood pressure and systemic vascular resistance indices when compared with those of the rest of the study group. Analysis of Starling curves indicated that all patients had normal or hyperdynamic left ventricular function. A modest correlation was observed between central venous pressure and pulmonary capillary wedge pressure (r = 0.59). This disparity most likely results from the maintenance of normal to high cardiac output in the presence of an increased left ventricular afterload. The majority of patients with severe pregnancy-induced hypertension do have normal to high cardiac indices and pulmonary capillary wedge pressures accompanied by normal or hyperdynamic left ventricular function. This is true despite the presence of severe hypertension. PMID- 3348313 TI - Surfactant proteins in the diagnosis of fetal lung maturity. I. Predictive accuracy of the 35 kD protein, the lecithin/sphingomyelin ratio, and phosphatidylglycerol. AB - The concentration of the major surfactant protein with a molecular weight of 35 kD was determined in 469 amniotic fluid specimens from 284 pregnancies by the two site simultaneous immunoassay with monoclonal antibodies. The predictive accuracy of the 35 kD protein was compared with that of the lecithin/sphingomyelin ratio and phosphatidylglycerol (the lung profile). Immature levels of 35 kD protein (less than 0.6 micrograms/ml) predicted 59% of all cases of respiratory distress syndrome (RDS) with an accuracy of 91%, and mature levels of 35 kD protein (greater than 3.0 micrograms/ml) predicted 68% of all infants who did not have RDS with an accuracy of 100%. The overall accuracy of the 35 kD protein in predicting the risk of developing respiratory distress syndrome was similar to that of the lung profile. In addition, testing with 35 kD protein improved the predictive value of an indeterminate lung profile (lecithin/sphingomyelin ratio of 1:1.9 and no phosphatidylglycerol) from 52% to 74%. The present results show that the lecithin/sphingomyelin ratio, phosphatidylglycerol, and 35 kD apoprotein have additive effects in improving the accuracy of the diagnosis of lung maturity. PMID- 3348314 TI - Pregnancy outcomes after successful chemotherapy for choriocarcinoma and invasive mole: long-term follow-up. AB - In order to preserve the fertility of young patients with choriocarcinoma and invasive mole, chemotherapy alone was given without hysterectomy in 265 cases from 1959 through 1980. By the end of 1985, 205 patients had become pregnant after recovery, with a total of 355 pregnancies. Among these, 23 were terminated by induced abortions, 26 as miscarriages, two as ectopic gestations, two as intrauterine deaths, and three as stillbirths. Among 303 livebirths (including four sets of twins), six infants died neonatally, three of whom were found to have congenital anomalies incompatible with life, and two died during infancy. All the remaining 295 children had normal growth and development, the oldest now being 25 years of age. The rates of fetal wastage, malformations, twin pregnancies, and neonatal and infantile deaths did not deviate from the normal. Cytogenetic study of the peripheral lymphocytes of 94 of the children revealed no increase of chromosomal aberrations. The rates of recurrence of disease and of death caused by recurrence of disease in these were not increased in comparison with those in patients who underwent hysterectomy. These data indicate that treatment of malignant trophoblastic neoplasms with chemotherapy alone is compatible with the preservation of fertility in most women. PMID- 3348316 TI - Distribution of K vitamins (phylloquinone and menaquinones) in human placenta and maternal and umbilical cord plasma. AB - It is a well-known fact that neonatal and infantile vitamin K deficiencies cause melena neonatorum and intracranial hemorrhagic disorders. These disorders occur more frequently in breast-fed babies than in bottle-fed babies, for reasons that are still obscure. Endogenous concentrations of K vitamins (phylloquinone and menaquinones) in human placentas and in paired specimens of maternal and umbilical cord plasma were detected by high-performance liquid chromatography with fluorometric detection and postcolumn reduction. Phylloquinone (K1) and menaquinones (MK-4, MK-6, and MK-7) were found in placentas and maternal plasma. K1 and MK-4 were found in umbilical cord plasma. The experimental subjects were 13 pregnant women with normal diets (group A) and two pregnant women with diets supplemented with fermented soybeans (group B), in which MK-7 is abundant. Samples from their placentas and maternal and umbilical cord plasma were collected just after delivery. The placentas and maternal plasma of group B contained higher concentrations of MK-7 (placentas = 10.82 ng/gm and maternal plasma = 3.55 ng/ml) than did group A (placentas = 1.08 ng/gm, maternal plasma = 0.70 ng/ml). However, MK-7 was not found in umbilical cord plasma of any of the subjects. The mean K1 values of all 15 patients in placentas and maternal and umbilical cord plasma were 1.28 ng/gm, 1.54 ng/ml, and 0.11 ng/ml, respectively; mean MK-4 values were 1.18 ng/gm, 0.05 ng/ml, and 0.04 ng/ml, respectively. A high concentration of MK-4 was detected in placentas. PMID- 3348315 TI - Prenatal detection of fetal thymidine kinase activity in maternal plasma: normal values and clinical application in postterm pregnancy. AB - Deoxythymidine kinase is present in human cells in two forms: the cytosolar form (fetal thymidine kinase) and the mitochondrial form (adult thymidine kinase). The activity of thymidine kinase isozymes in plasma of preterm and term newborns has been previously reported to be related to gestational age, and fetal thymidine kinase activity was reported to be undetectable after the thirty-ninth week of gestation. Our purpose was to determine if similar changes in the activity levels of the thymidine kinase isozymes could be demonstrated in late third trimester maternal plasma. A cross-sectional sample of 35 patients was studied from week 34 of pregnancy to delivery. Significant differences between fetal and adult thymidine kinase activity patterns were observed. Adult thymidine kinase activity remained relatively constant throughout the evaluation interval, while fetal thymidine kinase activity decreased with advancing gestational age. Regression analysis of gestational age by neonatal examination (GAPED) and fetal thymidine kinase revealed a linear relationship (fetal thymidine kinase = 0.380 - 0.00745 GAPED; R2 = 0.2944; standard estimate of error = 0.0350; p less than 0.0008). Comparison of fetal thymidine kinase activity in term and postterm pregnancy plasma revealed a significant difference (p less than 0.0159). Our findings indicate that deoxythymidine kinase activity can be measured in maternal plasma, may relate to the fetoplacental growth rate, and may be useful in differentiating between term and postterm gestations. PMID- 3348317 TI - Direct treatment of fetal supraventricular tachycardia after failed transplacental therapy. AB - Digitalization by direct intramuscular injection of the fetus successfully controlled supraventricular tachycardia at 24 weeks' gestation after more traditional intensive trials of transplacental therapy with digoxin, verapamil, and procainamide, either separately or in combination, had failed. The fetal pharmacokinetics were calculated from fetal blood samples obtained by cordocentesis. No clear evidence of placental transfer of digoxin administered to the mother could be found despite a digoxin concentration in the mother that ranged from 1.8 to 2.6 ng/ml for 4 days. After direct fetal digitalization we calculated that the coefficient of elimination for digoxin from the fetus was 0.0463 h-1, and digoxin elimination half-life was 15.9 hours. The latter time span is substantially less than the 50-hour half-life previously reported in newborn infants with low birth weight. The fetal/maternal concentration ratio of procainamide was 0.914. However, maternal clearance of procainamide (9.7 ml/kg 1/min-1) was twice as long as the clearance reported for nonpregnant patients undergoing fast acetylation. We conclude first, that at least in the dose of this ill fetus, little digoxin administered to the mother crossed the placentae; and second, that while direct fetal therapy with digoxin is effective, the necessary frequent number of injections render this therapy impractical. Direct fetal digitalization should probably be reserved for the preterm fetus who has evidence of heart failure and has not responded to maternally administered therapy other than digoxin. PMID- 3348318 TI - Neu-Laxova syndrome: a case report. AB - Neu-Laxova syndrome is a rare form of congenital malformation characterized by intrauterine growth retardation, microcephaly with bizarre facial features, short neck, apparent edema, scaly skin, and perinatal death. Chromosomal analysis in reported cases has revealed a normal karyotype, and an autosomal recessive transmission has been postulated. We present a case of Neu-Laxova syndrome. The pathologic features and the prenatal radiographic appearance are described. PMID- 3348319 TI - Ambulatory treatment of suspected pelvic inflammatory disease with Augmentin, with or without doxycycline. AB - Sixty-three women with suspected pelvic inflammatory disease were treated as outpatients with Augmentin with or without doxycycline. Initially, doxycycline was added only after a direct test for Chlamydia trachomatis was positive. Because chlamydial infections were frequent, all patients received doxycycline during the last two thirds of the study. Neisseria gonorrhoeae or Chlamydia trachomatis were recovered from 15 (65%) of 23 women classified as probably having pelvic inflammatory disease. Among 47 women reexamined after starting therapy, three rapidly became worse and were hospitalized, nine (20%) discontinued therapy because of gastrointestinal side effects, and all of the remaining 35 women who completed therapy were either cured or improved. PMID- 3348320 TI - Prolactin in human milk: the influence of nursing and the duration of postpartum lactation. AB - The concentrations of prolactin in the milk of nine postpartum lactating mothers were determined by radioimmunoassay between days 3 to 280 of the puerperium (n = 324 samples). In addition, prolactin in milk was also determined at the beginning and the end of suckling in three of the same women, who provided 21 paired samples of foremilk and hindmilk between days 7 and 88 of the puerperium. Prolactin content was highest at 43.1 +/- 4 ng/ml (mean +/- SEM) in the early transition milk immediately after the colostrum phase during the first postpartum week, decreasing to 11.0 +/- 1.4 ng/ml in the mature milk (p less than 0.01) when weaning occurred in those mothers who breastfed for up to 40 weeks post partum. During suckling, the foremilk contained significantly more prolactin as compared with the hindmilk (29.5 +/- 2.7 versus 21.0 +/- 3.2 ng/ml; p less than 0.01). These findings, taken together with the known biologic potency of prolactin in breast milk, the osmoregulatory influence of the hormone in mammary and intestinal function, and its absorption by the newborn experimental animal, suggest that the presence of prolactin in milk may play some role in both lactation and the intestinal absorptive function of the suckling newborn. PMID- 3348321 TI - Acyclovir in human breast milk. AB - Acyclovir concentration was measured by radioimmunoassay in the serum and milk of a lactating woman who was treated with oral acyclovir for herpes zoster. Daily serum and milk samples showing milk concentrations that averaged being 3.24-fold higher than serum levels suggest a low infant dose. The elimination phase demonstrated a half-life of 2.8 hours in milk. PMID- 3348322 TI - Autoantibodies and common idiotypes in men and women with sperm antibodies. AB - Antisperm antibodies have been implicated as a causative factor of infertility and pregnancy wastage. Since concomitant autoimmune phenomena were reported in men with antisperm antibodies, we investigated known antisperm antibody-positive sera from 25 women, 27 men, and the respective seminal plasma samples. The investigated autoimmune panel included a search for antinuclear antibodies, autoantibodies (in IgG, IgM and IgA isotypes) to seven phospholipids (cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid), to four histone subfractions (H1, H2A, H3, H4), and to four polynucleotides [ssDNA, dsDNA, poly(I), and poly(dT)], total immunoglobulin levels, and sperm antibody titers. The sera were also evaluated for the presence of a common anti deoxyribonucleic acid antibody, and anticardiolipin antibody idiotypes. Levels of sperm antibody titers were significantly lower in women than in men. Both men and women with antisperm antibodies demonstrated elevated total IgG levels compared with those of normal control subjects. Only women showed elevated levels of total IgM. Sera from 24% of women and 11% of men with antisperm antibodies demonstrated antinuclear antibody titers greater than 1:40. The most striking autoantibody abnormalities were found among antiphospholipid antibodies. Sera from women with antisperm antibodies demonstrated higher autoantibody production than was found in their male counterparts. A significant correlation was found between antisperm antibodies and IgM anticardiolipin and IgA anti-phosphatidylinositol in women and between sperm antibodies and IgA phosphatidylserine antibodies in men. The presence of anticardiolipin and anti-deoxyribonucleic acid antibody idiotypes was significantly more frequent in women than in men. By means of discriminant analysis and variables selected by this mathematical model, the identification of 24 of 25 women and 26 of 27 men with antisperm antibodies was correctly predicted. These results suggest that women and men respond differently to sperm antigens. The apparent cross-reactivity between sperm antibodies and other autoantibodies, usually associated with autoimmune disease, suggests that a polyclonal B cell activation, similar to that seen in autoimmune diseases, occurs in patients with sperm antibodies. PMID- 3348323 TI - Effect of abstinence on sperm motility in normal men. AB - We investigated the effect of varying the length of ejaculatory abstinence on sperm motility by a method of automated videomicrography. Ten fertile donors to an artificial insemination clinic provided semen samples at randomly assigned intervals of 12, 24, 72, and 120 hours. All specimens were produced on site, immediately incubated at 37 degrees C, and processed in triplicate. In comparing ejaculates obtained after 12 hours' abstinence with those after 120 hours, semen volume and sperm concentration demonstrated a significant increase with increasing abstinence time (p = 0.03). However, no correlation between abstinence time and percentage of motility, lateral head amplitude, cross-beat frequency, mean velocity, and mean linearity was found. We conclude that motility does not change with ejaculatory frequency and that in normal men prescribed abstinence before analysis of semen for motility characterization may not be necessary. PMID- 3348324 TI - Analytical versus clinical sensitivity and specificity in pregnancy testing. AB - A typical urine pregnancy test with the enzyme-linked immunoassay for human chorionic gonadotropin (Tandem Icon human chorionic gonadotropin) was performed as was a qualitative serum radioimmunoassay for human chorionic gonadotropin when the positive cutoff for the latter was set at 30 IU/L. There was 99.5% concordance between the two methods when performed on 871 simultaneous urine and serum specimens. Although the serum radioimmunoassay can detect levels of human chorionic gonadotropin as low as 10 IU/L, in this study the majority of patients with serum levels between 10 and 30 IU/L were not pregnant on clinical follow-up. Of nine patients with adequate clinical follow-up, a negative urine pregnancy test result, and a serum human chorionic gonadotropin level between 10 and 30 IU/L, only one proved to be pregnant. The Tandem Icon human chorionic gonadotropin urine test is sufficient for routine pregnancy testing and to rule out the need for immediate intervention in cases of ectopic pregnancy. PMID- 3348325 TI - Suing as an expression of somatization. AB - We suggest that some litigation may be an expression of somatization in which primarily psychological processes are expressed through legal activity rather than through bodily oriented, functional symptoms. PMID- 3348326 TI - The resident and fellow relationship in obstetrics and gynecology. AB - In a nationwide survey, chief administrative residents reported their views on how subspecialty fellowships affect their residency training in obstetrics and gynecology. The residents felt that fellows improve the quality of their training, depending on the degree they consider fellows as junior faculty involved in teaching and modeling patient care. Competition for surgical cases, and the surgical priority fellows have over residents in the new technology and nonroutine cases, potentially detract from the resident-fellow training relationship. These factors varied by subspecialty and the particular content areas of the fellowship. The residents' comments highlight the positive and negative components of each fellowship and identify the features of their relationship with the fellows. The implications of these findings for enhancing this relationship are presented. PMID- 3348327 TI - A comparison of resident and program director views on the effects of subspecialty fellowships on residency training in obstetrics and gynecology. AB - In separate nationwide surveys, chief administrative residents and residency program directors reported their views on the impact of subspecialty fellowships on residency training. The residents expressed a less positive view of the fellowships, but like the directors, considered them beneficial to their training. The directors underestimated the degree residents regret the loss of operative experiences to the fellows, particularly in laser surgery, infertility surgery, and radical pelvic surgery. Within a given residency program, resident and program director opinions of the fellowships appear unrelated or contradictory. The implications of these findings for a discussion between residents and program directors are presented. PMID- 3348328 TI - Progesterone and dexamethasone inhibition of uterine epithelial proliferation in two models of estrogen-independent growth. AB - It is believed that progestins and glucocorticoids block estrogen-induced growth of the uterus by perturbing the mechanism of estrogen stimulation. We have examined the effect of progesterone or dexamethasone on two rodent models of estrogen-independent proliferation of uterine epithelium. Tissues of the neonatal mouse uterus exhibit high rates of deoxyribonucleic acid synthesis in the absence of endogenous steroids. Progesterone and dexamethasone inhibit deoxyribonucleic acid synthesis in the uterine epithelium of 4-day-old mice. When grafted beneath the kidney capsule of an ovariectomized adult, the tissues of the neonatal uterus continue to grow without the addition of estrogen. Both progesterone and dexamethasone blocked uterine epithelial mitotic activity in these allografts. A true growth response can be stimulated in the uterus of an ovariectomized rat by intraluminal instillation of cholera toxin. In the present study, autoradiographic analysis showed that cholera toxin stimulation of deoxyribonucleic acid synthesis was confined to the epithelial compartment in ovariectomized, vehicle-treated rats. When ovariectomized rats were pretreated with progesterone, cholera toxin induced deoxyribonucleic acid synthesis in the stroma but not in the epithelium. Thus progesterone and dexamethasone inhibit uterine epithelial proliferation that is not driven by estrogen stimulation. Therefore in these estrogen-independent model systems, the inhibitory effects of these steroids cannot be due to antagonism of estrogen receptor--mediated events. These observations suggest that inhibition in estrogen-induced uterine epithelial proliferation may also work through a mechanism unrelated to antagonism of estrogen receptor action. PMID- 3348329 TI - Fuel-mediated teratogenesis: symmetric growth retardation in the rat fetus at term after a circumscribed exposure to D-mannose during organogenesis. AB - We previously infused the D-glucose epimer D-mannose into pregnant rats to deliver a brief metabolic insult to the early postimplantation conceptus. This insult caused developmental anomalies and growth retardation that were apparent in the embryos 2 days later. We now report the long-range effects on intrauterine development of such a circumscribed metabolic insult during organogenesis. Ten pregnant animals were infused with D-mannose for 12 hours during early neurulation (day 9.5 to 10 of development). Ten control animals were infused with equimolar D-glucose during this same time interval. Mannose infusions produced maternal plasma mananose concentrations in the embryotoxic range; glucose infusions caused only slight and transient hyperglycemia. Fetuses were removed at term and examined for evidence of developmental anomalies and growth retardation. None of 137 fetuses from the mannose group or 138 fetuses from the glucose group exhibited gross anomalies. However, an excess of resorbed conceptions in the mannose group (21 versus six in the glucose group; p less than 0.01) suggested some lethal toxicity from mannose exposure during embryogenesis. Among viable fetuses, the mean body weight of those from the mannose group was significantly reduced compared with those from the glucose group (5.62 +/- 0.04 versus 5.89 +/- 0.03 gm, respectively; p less than 0.001). Reductions of a similar magnitude were noted in the mean wet weight and protein content of fetal brains, hearts, livers, and kidneys from the mannose group (range, 3.4% to 7.1% below the glucose group), indicating a symmetric pattern of fetal growth retardation. In addition, analysis of fetal ossification sites after Alizarin Red S staining revealed a significant delay of skeletal development in the mannose group. These results indicate that a relatively brief metabolic insult to embryos during early organogenesis may cause lethal developmental anomalies as well as growth retardation and delayed skeletal development that are manifested in the fetus at term. PMID- 3348330 TI - Intravascular neuromuscular blockade for fetal transfusion. PMID- 3348331 TI - Diabetic control in pregnancy. PMID- 3348332 TI - Change in International Federation of Gynecology and Obstetrics staging. PMID- 3348333 TI - Amniotic fluid embolism and leukotrienes. PMID- 3348334 TI - Prenatal steroid for the prevention of respiratory distress. PMID- 3348335 TI - Evaluation of three clinical tests for predicting pregnancy-induced hypertension. PMID- 3348336 TI - Professional involvement in sexuality counseling for patients with spinal cord injuries. AB - A national survey was conducted to determine how occupational therapists and rehabilitation nurses conduct sexuality counseling in practice settings with spinal cord-injured patients. A review of the literature and results from the survey demonstrated a high priority concern for sexuality counseling in the total rehabilitation of the spinal cord-injured patient; however, many of the professionals surveyed did not conduct sexuality counseling as part of their job. This study provides data comparing the sexuality counseling approach taken by these two disciplines and identifies ways to eliminate the incongruities between recommendations made in the literature and actual clinical practice. PMID- 3348337 TI - Aquatic therapy for an ALS patient. AB - The opportunity to participate in wellness programming can be particularly valuable to persons who must be prepared to deal with continuing gradual physical deterioration for the rest of their lives. During time periods when his health was stable, without evidence of a rapid progression of the illness, Charlie was able to devote some energy to the pursuit of swimming, an activity he had enjoyed for many years. The WETSwim program provided the opportunity for Charlie to take an active role in the management of his physical and psychological status. In an environment where he was able to overcome barriers to participation, Charlie could explore aquatic recreation activities and resume a leisure role. He experienced the opportunity to learn and practice swimming skills, develop an area of performance to a mastery level, and improve his quality of life. Occupational therapists are no longer confined to the traditional locations for and methods of providing treatment. Encouraged by the changing economics of health care, they seek alternative ways of providing quality health care (Frazian, 1985). Persons with short-term physical dysfunction, as modern consumers, are taking greater initiative in the medical management of their dysfunction and seek alternatives to passive forms of treatment. Persons with chronic or long-term physical disabilities, in addition to having basic needs for optimal sensory-motor function and ADL independence, are becoming increasingly interested in physical fitness. The WETSwim program offers a wide range of opportunities, medical and recreational, functional and social, to the consumer with physical dysfunctions. PMID- 3348338 TI - Promoting occupational therapy by using a simulated hemiplegic arm to demonstrate dressing technique. AB - When creating a promotional booth to increase awareness about occupational therapy remember that (a) people learn by participating and (b) positive reinforcement encourages a greater sense of learning. In addition, follow these rules: (a) keep the task simple, (b) eliminate jargon and use nonmedical terms, (c) encourage interaction and reward thoughtful reflections, and (d) make sure that participants leave with some promotional materials in hand. As described here participants acquired a hemiplegic arm and tried to dress. They were immediately rewarded with an occupational therapy sticker. Acting as patients, they experienced visual deficits with a special pair of glasses. The occupational therapist encouraged people to ask questions about dressing and visual deficits and about the display of splints and adaptive equipment. People helped themselves to occupational therapy promotional buttons and literature. They left with a basic understanding of hemiplegia. They also understood how an occupational therapist works with a patient to help the patient regain functional independence. PMID- 3348339 TI - Ethical considerations for research in occupational therapy. PMID- 3348340 TI - Certification: serving the public interest. AB - The certification program has undergone an exciting change. The AOTA leadership and AOTA members are to be applauded for making this important step. The AOTCB is still a fledgling organization; nonetheless, it has already made great strides in carrying out its mission. The AOTCB will continue to build on the very excellent foundation AOTA has laid for the certification program. The AOTCB welcomes questions, comments, and suggestions concerning the certification program. To contact AOTCB, write to AOTCB, 1383 Piccard Drive, Rockville, MD 20850-4375 or call (301) 948-9626. PMID- 3348341 TI - Comparison of myoelectric and conventional prostheses for adolescent amputees. AB - We questioned whether myoelectric prostheses were a reasonable alternative to conventional prostheses for adolescents with unilateral, congenital, below-elbow amputations in respect to fit, function, cosmesis, and cost. Ten patients were studied. Each received a physical, functional, and psychosocial evaluation prior to prosthetic fitting. The physical evaluation included myopotential, residual limb length and circumference, active range of motion, terminal device grasp force, and mechanical range. The functional evaluation consisted of a questionnaire of 38 bimanual activities. The psychosocial evaluation included an assessment of both the patient and the family. Following prosthesis fabrication, each patient received 10 days of training, a 3-month checkup, and a 6-month reevaluation. Wearing patterns, perception of cosmesis, change in physical attributes of the residual limb, and functional performance were documented. Results indicate that for these subjects myoelectric prostheses with a hand were an acceptable alternative to conventional prostheses with a hook. PMID- 3348342 TI - The OSOT Perceptual Evaluation: a research perspective. AB - Although the Ontario Society of Occupational Therapists (OSOT) Perceptual Evaluation has been widely used, it has never been standardized. A study was undertaken to examine the validity of the battery for differentiating neurologically normal persons from those who have been independently diagnosed as neurologically impaired. A group of 80 brain-damaged patients was compared with a matched group of 70 neurologically normal persons. Comparison of scores for the two groups supports the validity of the instrument for differentiating the neurologically normal from the perceptually impaired person. The distribution of scores suggests that the degree of impairment can be classified as mild, moderate, or severe. Finally, the OSOT Perceptual Evaluation is found to be a reliable procedure for the assessment of perceptual dysfunction. PMID- 3348343 TI - Praxis and gesture comprehension in 4-, 5-, and 6-year-olds. AB - This investigation examined (a) whether the ability to comprehend pantomimed gestures improves with age in young children and whether the ability to point to the actual object precedes the ability to point to a functional associate and (b) whether there is a difference in the ability to comprehend pantomimed gestures between learning-disabled and normal subjects. The Gesture Comprehension Test, the Imitation of Postures test, and the Test for Auditory Comprehension of Language were administered to 68 normal children and 24 learning-disabled children 4 to 6 years of age. Results indicated that gesture comprehension improved with age and that the ability to point to the actual object preceded the ability to point to its functional associate. Boys performed significantly better than girls. There was no significant difference between normal and learning disabled subjects' ability to comprehend gestures. A moderate correlation was found between the Gesture Comprehension Test and the Test for Auditory Comprehension of Language; a low correlation was found between the Gesture Comprehension Test and the Imitation of Postures test. These results suggest the possibility that in preschool children and young school-age children, gesture comprehension may be more closely related to language than to nonsymbolic aspects of praxis. PMID- 3348344 TI - Horizontal and vertical vergence training and its effect on vergences and fixation disparity curves: I. Horizontal data. AB - The purpose of this study was to assess the effects of horizontal and vertical vergence training on fusional vergences and the fixation disparity (FD) curve. Thirty-four subjects were divided into three groups. One-third served as controls and the other two-thirds underwent 5 h of supervised horizontal and vertical vergence training, respectively. Before and after the 4 week training period, vergences and FD curves were measured by a single individual who was intentionally uninformed of each subject's group. We hypothesized that the subjects in the horizontal training group would have increased vergence amplitudes and flatter FD slopes. Our analysis revealed that the positive vergences increased significantly for those in the horizontal group. No evidence was found to suggest changes in any variables related to the FD curve. Because type II errors were likely to be unacceptably large, further work is necessary to determine the relation between fusional vergence training and variables derived from the FD curve. PMID- 3348346 TI - Corneal oxygen availability during contact lens wear: a comparison of methodologies. AB - Three distinct methodologies have been used to assess corneal oxygen supply during contact lens wear--oxygen transmissibility (Dk/L), equivalent oxygen percentage (EOP), and corneal swelling. To examine the interelation among these methodologies, we measured the EOP and the amount of corneal swelling in response to a set of contact lenses of a range of Dk/L values on 10 subjects. We also measured the corneal swelling response after exposure to gas mixtures of 0.00, 1.01, 2.65, 5.13, and 10.3% oxygen concentration (balance nitrogen). Analysis of covariance showed that the relation between corneal swelling and EOP during lens wear was significantly different from the relation between corneal swelling and oxygen concentration after exposure to the gas mixtures, leading to different estimates of the minimum oxygen tension required to avoid corneal swelling (18.0% for the EOP technique vs. 10.9% for the gas mixtures). This discrepancy may be explained in terms of the underlying assumptions of the various techniques and by consideration of the mechanisms of corneal swelling during contact lens wear. The clinical implication of this result is that an EOP of 18% should be used as the basis for the development of a daily wear contact lens that provides an "edemafree" response. PMID- 3348345 TI - Monovision contact lens wear and occupational task performance. AB - The effects of monovision (MV) contact lens wear on the performance of occupational-type nearpoint tasks was evaluated on 18 presbyopic subjects (ages 44 to 67 years) by comparing MV performance (MV condition) to that with distance contact lenses with reading glasses (BV condition). Each subject had correctable distance visual acuity of 6/6 (20/20) in each eye, at least 60 sec arc of near stereopsis, good ocular health, and no previous MV experience. Time performance and error performance for 3 nearpoint occupational tasks (pointers and straws, card filing, and letter editing) were measured with the MV correction and BV correction. Measurements were taken at dispensing and at 2 weeks and 8 weeks after dispensing. Subjects were instructed to wear the MV soft spherical contact lenses at least 8 h per day. We measured BV time performance to be better than MV time performance by 2.8 to 5.7% and also measured an increased number of errors with MV. PMID- 3348348 TI - Correlation of nerve head and blind spot elliptical features. AB - Ellipses were fitted to 129 nerve heads and corresponding blind spots in an attempt to determine how faithfully the elliptical nature of the nerve head is reflected in the blind spot. The blind spots are found to be 2 to 3 times more elliptical (based on the ratio of the long axis to the short axis) than the nerve heads. The correlation between the ratios mentioned above is found to be negligible (Pearson r = 0.07 for Goldmann 1-2 blind spots and 0.18 for Goldmann 1 4 blind spots). PMID- 3348347 TI - Effect of chromatic dispersion of a lens on visual acuity. AB - Materials with a high refractive index have a considerable level of chromatic dispersion which, around the periphery of corrective lenses, may affect the wearer's visual acuity. By measuring visual acuity through prisms of increasing chromatic power we have established the relation between chromatic power and visual acuity. The maximum chromatic dispersion of materials useable in ophthalmic optics can be deduced from these results. PMID- 3348349 TI - Reliabilities of alternate measures of contrast sensitivity functions. AB - In four studies, the comparability of several measures of contrast sensitivity functions (CSF's) as well as their individual test-retest reliabilities were determined with observers drawn from a college population. The relation between CSF scores obtained by different tests or by different psychophysical procedures with the same test was consistently low and frequently nonexistent. These low intertest reliabilities were found to be due to the lack of reliability of some of the individual tests. In particular, with both stationary and flickering gratings, the von Bekesy tracking procedure produced unacceptable variations in contrast estimates. Fortunately, the reliabilities of other procedures, particularly the simple adjustment method, were much higher (greater than 0.70). CSF scores obtained from the wallchart method exhibited insufficient variability among observers in the college sample to permit similar reliability estimates to be determined. Implications of the test characteristics are discussed for users of the CSF. PMID- 3348350 TI - Effect of induced aniseikonia on fixation performance. AB - The purpose of the study was to determine to what extent induced aniseikonia affects fixation performance. Aniseikonia was induced in the vertical meridian only, whereas fixation alignment was monitored in the horizontal meridian. A previously developed technique based on the dependency of border enhancement bandwidth on fixation eccentricity was used to monitor deviations from central fixation during fusion. Stress on the fusion mechanism was supplied by controlled increments of forced horizontal vergence. It was found that deviation from central fixation in the horizontal meridian generally increases with increasing amounts of vertical aniseikonia. The effect is particularly pronounced for small amounts of aniseikonia. PMID- 3348351 TI - Optometric findings during pregnancy. PMID- 3348352 TI - The effect of volition on the horizontal forced-vergence fixation disparity curve. AB - An anomalous horizontal forced-vergence fixation disparity curve in the shape of the letters V or U is presented. This phenomenon is associated with an increase in eso fixation disparity with base-out prism. This response is shown to be related to instructional set. Intrusion of voluntary vergence is suggested as the most likely basis for this effect. PMID- 3348353 TI - Possible role of ascorbate in induction of ocular neoplasia by visible light. PMID- 3348354 TI - Horizontal and vertical vergence training and its effect on vergences, fixation disparity curves, and prism adaptation: II. Vertical data. AB - The purpose of this study was to assess the effects of horizontal and vertical vergence training on vertical fusional amplitudes, the vertical fixation disparity (VFD) curve, and prism adaptation. Thirty-four subjects were divided into three groups. One-third served as controls and the other two-thirds underwent 5 h of supervised horizontal and vertical vergence training, respectively. We hypothesized that subjects in the vertical group would manifest increased vertical vergence amplitude and coefficients of adaptation in concert with flatter VFD slopes. Before and after the 4-week training period, vertical vergences, fixation disparity (FD) curves, and coefficients of vertical prism adaptation were measured by a single individual who was intentionally uninformed of each subject's group. Analysis of the data suggests that changes in the vertical fusional amplitudes increased slightly. Although changes in the VFD slope and coefficient of prism adaptation were not statistically significant, the changes were much greater in the vertical group and in the hypothesized direction. We suggest that the results offer preliminary support for our hypothesis. PMID- 3348355 TI - DNA profiles in mitotic cells from gastric adenomas. AB - Quantitative DNA measurements were done in mitotic figures from 17 gastric adenomas having slight (3 cases), moderate (8 cases), or severe dysplasia (3 cases) or foci of invasive adenocarcinoma (3 cases). Values higher than for normal diploid control cells (2c) or their estimated tetraploid values (4c) were found to increase gradually from slight dysplasia to invasive adenocarcinoma through moderate and severe dysplasia. While none of the adenomas having slight or moderate dysplasia demonstrated aneuploid mitoses (ie, values higher than 5c), 1% of the mitoses in severe dysplasia and 27% of those with invasive adenocarcinoma had values higher than 5c. The present results thus suggest that aneuploid mitotic figures may help to recognize those gastric adenomas having invasive growth. PMID- 3348356 TI - Correlation between differentiation and lung colonization by retinoic acid treated F9 cells as revealed by the expression pattern of extracellular matrix and cell surface antigens. AB - For study of the correlation between differentiation and organ colonization properties of tumor cells, F9 embryonal carcinoma (EC) cells were treated with retinoic acid, an inducer of differentiation; and their organ colonization pattern was assessed by the experimental metastasis assay. Untreated cells were found to colonize the liver, whereas treated cells colonized the lungs. This pattern held true when metastases were scored after spontaneous death or after a careful microscopic search for micrometastases. Histologic examination revealed that both the tumor nodules produced by the untreated and the treated cells had the characteristics of EC devoid of any evidence of differentiation. The immunohistochemical study of the expression of markers typical of embryonal carcinoma cells or of the extracellular matrix components laminin and collagen type IV, typical of differentiated cells, confirmed these results. However, the lack of expression of stage-specific embryonal antigen 1 (SSEA-1), a marker generally associated with the undifferentiated state, observed only in the tumors obtained after injection of treated cells, indicates that the lung nodules probably derive from cells that have responded to the induction in vitro but have dedifferentiated in vivo. PMID- 3348357 TI - Negative correlations between parenchymal amyloid and vascular amyloid in hippocampus. AB - Congo red was used to stain amyloid in 29 blocks of hippocampus from 17 unselected cases of Alzheimer's disease. Green birefringence under polarized light was used for evaluation of the average number of senile plaques and cross sectional vessel profiles containing amyloid in five fields per slide, at a magnification of X100. Fields were selected that had large numbers of neurofibrillary tangles, also counted on the basis of green birefringence. The vascular involvement by amyloid was expressed as the ratio of amyloid positive to amyloid negative profiles. A negative correlation was found between Congophilic plaques or tangles on the one hand and vascular amyloid content on the other. In other words, cases with large numbers of Congophilic plaques had fewer Congophilic vessels, and vice versa: congophilic plaques = -3 (vessel amyloid) + 2.2, Spearman correlation coefficient, -0.61, P less than 0.01; tangles = -3.7 (vessel amyloid) + 15.6, Spearman correlation coefficient, -0.05, P greater than 0.05. When the slides were reexamined, using only fields with at least one Congophilic vessel, the negative correlation for plaque versus vessel amyloid remained highly significant, whereas that for tangles versus vessel amyloid became highly significant: Congophilic plaques = -1.2 (vessel amyloid) + 2.3, Spearman correlation coefficient, -0.48, P less than 0.01; tangles = -5 (vessel amyloid) + 19, Spearman correlation coefficient, -0.48, P less than 0.01. These data are most compatible with the hypothesis that amyloid is first produced in the parenchyma and is somehow cleared by the vessels. It is least compatible with the hypothesis that the amyloid precursor protein first enters the vessel wall to produce amyloid there, and then moves into the brain to produce amyloid in parenchymal sites. PMID- 3348358 TI - Contribution of oxygen-derived free radicals to experimental necrotizing enterocolitis. AB - Oxygen-derived free radicals, particularly superoxide anion, are considered important mediators of intestinal injury induced by ischemia/reperfusion based on the protective effects of superoxide dismutase and allopurinol. A role for free radicals was investigated in a model of necrotizing enterocolitis (NEC) which was initiated by a luminal, as opposed to a vascular, insult. Intestinal loops of weanling rabbits received either saline (control loops) or a solution of 10 mg/ml casein and 50 mg/ml calcium gluconate acidified to pH 4 with proprionic acid (treated loops). When the animals were sacrificed 3 hours later, severe damage was noted in the treated loops, which included blunting of villi and edema, with all animals surviving. At 16 hours only 5 of 8 rabbits survived, and 3 had hemorrhagic necrosis. Control loops were normal in each case. Intravenous infusion of superoxide dismutase (4 mg/kg/hr), commencing 15 minutes after NEC induction, totally prevented intestinal injury. On the other hand, pretreatment with allopurinol, an inhibitor of xanthine oxidase, for 2 days (30 and 60 mg/kg by mouth) was not protective against intestinal damage. A cellular infiltration in treated loops was not histologically evident in the majority of animals at 3 hours after treatment, a finding confirmed by the minimal accumulation of 111In labeled leukocytes in damaged and intact intestinal tissue. These results suggest that superoxide generated locally from sources other than xanthine oxidase play a critical and early role in experimental NEC and that superoxide dismutase may prove to be an effective therapy in this devastating neonatal disease. PMID- 3348359 TI - Isolation of a major protein component of Rosenthal fibers. AB - Rosenthal fibers (RFs) are inclusions within astrocytes, characteristic of Alexander's disease, but also seen in astrocytic tumors and occasionally in glial scar tissue. They are granular deposits, intimately associated with intermediate filaments. Their composition has been unknown. The authors have isolated a protein of about 19 kd from partially purified RFs from Alexander's disease central nervous system tissue. Antibodies were raised to this protein and shown to react with it on nitrocellulose blots and to bind to RFs in tissue sections. Small amounts of this protein were detected in normal brain and in cultured rat astrocytes. Charge heterogeneity was inferred because several species were separated by isoelectric focusing. PMID- 3348360 TI - Age-related and site-specific adaptation of the arterial endothelial cytoskeleton during atherogenesis. AB - The authors probed the vascular endothelial cell cytoskeleton in strains of pigeons that are atherosclerosis-susceptible and disease-resistant, namely, the White Carneau and Show Racer pigeons. Endothelial cell actin and myosin were localized with the use of affinity-purified antibodies in conjunction with indirect immunofluorescence microscopy. The endothelial cell cytoskeleton was characterized in a site-specific and time-dependent manner by examination of arterial segments from each strain of pigeons. Anti-actin and anti-myosin fluorescence staining patterns of endothelial cells lining the ascending aorta, aortic arch, and thoracic aorta from the White Carneau and Show Racer pigeons sacrificed at 1 and 12 months of age were compared and analyzed. In the Show Racer, irrespective of arterial site or chronologic age, endothelial cell cytoskeletal organization is similar. Actin and myosin fluorescence is brightest at the cortex, where endothelial cells meet their neighbors. There is also an amorphous (diffuse) fluorescence throughout the cytoplasm. In addition to the diffuse and cortical cytoskeletal fluorescence in the endothelial cells of the Show Racers, the White Carneau also possess a unique cytoskeletal array of linear fluorescence, ie, the endothelial cell ridge. At 1 month of age, anti-actin staining of endothelial cell ridges averages 28.5 mu in length in the ascending aorta, 28.0 mu in the aortic arch, and 40.0 mu in the thoracic aorta. At the same time, anti-myosin fluorescence extends past both ends of the anti-actin-stained endothelial cell ridge fluorescence. In the ascending aorta, anti-myosin labeling of endothelial cell ridges is 3.5 times longer than anti-actin staining. This staining is absent in the aortic arch, whereas the thoracic aorta possesses endothelial cell ridges that extend over the entire length of the vessel segment. At 12 months of age, actin-stained endothelial cell ridges increase 1.6- and 1.4 fold in the ascending aorta and aortic arch, respectively. The thoracic aorta possesses endothelial cell ridges that cover its entire length. At 12 months of age, the length of myosin-stained endothelial cell ridges does not increase in the ascending or thoracic aorta. In contrast, the aortic arch expresses endothelial cell ridges that exceed 150 mu in length. It is proposed that the endothelial cell ridge assembles from cytoskeletal components as a focal endothelial cell response to injury, perhaps promoting endothelial cell adhesion to the underlying basal lamina through a transmembrane linkage. PMID- 3348361 TI - In vivo effects of transient neutrophil influx on nasal respiratory epithelial mucosubstances. Quantitative histochemistry. AB - Certain inhaled toxicants are known to induce mucous hypersecretion in the respiratory epithelium. This secretory change may be a direct effect of the toxicant or an indirect effect of the concomitant inflammatory response. The present study was designed to determine by quantitative histochemistry whether the influx of neutrophils through the nasal respiratory epithelium would induce significant quantitative changes in the amount of intraepithelially stored mucosubstance. F344/N rats were intranasally instilled with endotoxin to elicit a transient influx of neutrophils into the nasal epithelium. Peak intraepithelial infiltration of neutrophils was evident 6 hours after instillation. There was a concurrent quantitative decrease in stored epithelial mucosubstance at the same time after instillation. Amounts of epithelial mucosubstance returned to that measured prior to neutrophil infiltration by 24 hours after instillation, when intraepithelial neutrophils were diminishing. Rats in which circulating neutrophils were sequestered in the lungs and prevented from migrating into endotoxin-exposed nasal epithelium had no change in the quantity of stored mucosubstance 6 hours after instillation. Therefore, it is concluded that a transepithelial migration of neutrophils elicits a transient depletion of stored mucosubstances in the nasal respiratory epithelium. Whether this is due to the release of secretagogues from the migrating leukocytes or another neutrophil related method of stimulating mucous secretion is not known. PMID- 3348363 TI - Electrical properties of the gap junctional membrane studied in rat liver cell pairs. AB - Cell pairs isolated from adult rat liver were used to study the electrical properties of gap junctions. Each cell of a cell pair was connected to a suction pipette so as to enable whole cell tight-seal recording. A double voltage-clamp approach was adopted to control the voltage gradient across the gap junction and measure the transjunctional current. The current-voltage relationship of the gap junctional membrane was linear over the voltage range tested (+/- 50 m V). Under control conditions, the resistance of the gap junction, rj, was 15 M omega (n = 27; range, 4.6 to 45.8 M omega), corresponding to a conductance gj of 67 nS. rj was insensitive to the nonjunctional membrane potential, Vm (voltage range,-90 m V to + 40 m V). There was no indication of a time-dependent gating of rj (time range, 20 ms to 10 s). Dialysis with 1 mM CaCl2 produced irreversible electrical uncoupling without affecting the linearity of the relationship Vj/Ij. PMID- 3348362 TI - Effect of cell substrate on antioxidant enzyme activities in cultured renal glomerular epithelium. AB - The activities of three antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase, were monitored in isolated guinea pig glomeruli and primary or subcultured glomerular epithelial cells. Cell injury was assessed by morphologic studies and by measurement of cellular lipid peroxidation (levels of malondialdehyde). Antioxidant enzyme activities were very different in cultured cells than in parent glomeruli. The possible effect of culture substrates (tissue culture plastic, bovine corneal endothelial [BCE] cell basement membrane, and PF HR-9 endodermal cell basement membrane) on antioxidant enzyme status, cell morphology, and lipid peroxidation was also assessed. Glomerular epithelial cells cultured on the BCE cell basement membrane substrate survived longer and showed less lipid peroxidation than cells cultured on plastic or the HR-9 substrate. Cells cultured on a plastic substrate had substantially less glutathione peroxidase activity than cells cultured on either BCE or HR-9 basement membranes. PMID- 3348364 TI - Asymmetry of Na-K-Cl cotransport in human erythrocytes. AB - The Na-K-Cl cotransport system in human erythrocytes was studied by measuring net influxes and effluxes of Na and K. The influx of K was shown to be stimulated by Na and the influx of Na was stimulated by K, satisfying the fundamental criterion of cotransport. In addition, these mutually stimulating cation influxes had a stoichiometry of 1:1 and were entirely inhibited by furosemide; these results are also consistent with cotransport. Furthermore, the mutually stimulating influxes were entirely dependent on Cl, since they were abolished when nitrate was substituted for Cl. In contrast, cotransport, defined by mutual dependence of fluxes, was not detected in the outward direction over a range of cellular Na and K concentrations from 0 to 50 mmol/l cells. The cotransport pathway did, however, appear to mediate a Na-stimulated K efflux (but no K-stimulated Na efflux), and furosemide-inhibitable effluxes of both Na and K. Nitrate (but not sulfate) appeared to substitute for chloride in promoting Na-stimulated K efflux. Thus the Na-K-Cl cotransport system in human red cells is intrinsically asymmetric, and mediates coupled cation fluxes readily only in the inward direction. PMID- 3348366 TI - High-pressure pulsation of central and microvessel pulmonary artery endothelial cells. AB - We developed an in vitro method of pulsating central and microvessel pulmonary artery endothelial cells that would allow us to study the effects of increased distending pressures over a prolonged period of time. Preservation of the contact inhibited monolayer was assessed on phase contrast microscopy and, in addition, scanning and transmission electron microscopy (SEM, TEM) were used to determine whether there were alterations in the surface characteristics or intracytoplasmic organelles that suggested cellular damage. The cells used were obtained from Rambouillet lambs, age 3-5 days, anesthetized with halothane and ventilated. The endothelium was harvested from the central pulmonary artery (CPA) by scraping the luminal surface and from the microvessels (MPA) by infusing microcarrier beads 40 140 microns external diameter. After the second passage in culture, the cells were seeded onto the translucent, flexible polyvinylchloride membrane of a transducer dome and grown to confluence. The cell dome was then connected to a blank dome with an attached quartz transducer, to a reservoir, and to stainless steel bellows tubing, all filled with culture medium and affixed to a pulsation generator. By varying the height of the reservoir, the amplitude of excursion of the bellows tubing, and the rate, the cells could be pulsated at a given distending pressure and frequency. Confluent CPA endothelial cells from three lambs and MPA cells from two others were studied after pulsation at both 100/60 and 20/10 mmHg, 60 times/min for 48 h and after nonpulsation. On phase contrast light microscopy and on SEM, the cells remained confluent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348365 TI - In vivo 31P-NMR spectroscopy of chronically stimulated canine skeletal muscle. AB - Chronic stimulation converts skeletal muscle of mixed fiber type to a uniform muscle made up of type I, fatigue-resistant fibers. Here, the bioenergetic correlates of fatigue resistance in conditioned canine latissimus dorsi are assessed with in vivo phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After chronic electrical stimulation, five dogs underwent 31P-NMR spectroscopic and isometric tension measurements on conditioned and contralateral control muscle during stimulation for 200, 300, 500, and 800 ms of an 1,100-ms duty cycle. With stimulation, phosphocreatine (PCr) fell proportional to the degree of stimulation in both conditioned and control muscle but fell significantly less in conditioned muscle at all but the least intense stimulation period (200 ms). Isometric tension, expressed as a tension time index per gram muscle, was significantly greater in the conditioned muscle at the two longest stimulation periods. The overall small change in PCr and the lack of a plateau in tension observed in the conditioned muscle are similar to that seen in cardiac muscle during increased energy demand. This study indicates that the conditioned muscle's markedly enhanced resistance to fatigue is in part the result of its increased capacity for oxidative phosphorylation. PMID- 3348367 TI - Angiotensin II causes a dual effect on potassium permeability in adrenal glomerulosa cells. AB - In previous studies it was shown that angiotensin II causes a Ca-dependent increase in the K permeability of bovine adrenal glomerulosa cells [Am. J. Physiol. 250 (Endocrinol. Metab. 13): E125-E130, 1986]. Here we show that angiotensin II causes a significant and prolonged reduction in the 86Rb release immediately after the transient rise in 86Rb efflux. This inhibition was dose related. Apamin (100 nM) and tetraethylammonium (10 mM) completely abolished the initial transient rise in 86Rb efflux without affecting the latter sustained phase of reduced radioisotope release. On the contrary, the effect of angiotensin II on the second phase was absent when Ca was removed from the perifusion medium or replaced with Sr, but the effect on the early transient phase of 86Rb efflux was maintained in the absence of external Ca. An additional finding was the increased coefficient rate of 86Rb efflux that occurred when the cells were depolarized with 12 mM K. However, this effect was not observed when the inhibitory phase due to angiotensin II was fully developed and Ca was present in the external media. On the other hand, the biphasic effect of angiotensin II was still present in depolarized cells. These results suggest that angiotensin II may modulate membrane potential by changes in K permeability of the bovine adrenal glomerulosa cells. PMID- 3348368 TI - Metabolism of 25-hydroxyvitamin D in copper-laden rat: a model of Wilson's disease. AB - Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. We investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D3 [25(OH)D3] resulted in reduced 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in copper-intoxicated rats. In vitro 25(OH)D-1 alpha-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondria from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH)2D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease. PMID- 3348369 TI - Effect of hypophysectomy on energy balance and brown fat activity in obese Zucker rats. AB - Hypophysectomy (HYPX) in genetically obese (fa/fa) Zucker rats significantly reduced body weight and energy gains and stimulated energy expenditure (by 34%), the thermic response to food (by 144%), and brown adipose tissue (BAT) mitochondrial GDP-binding capacity (by 190%) compared with pair-fed, sham operated obese rats. These changes in energy balance in obese HYPX rats were reversed by corticosterone replacement (1 mg/day), but the increased BAT activity was only partly restored to normal. HYPX had only small effects on energy balance in lean Zucker rats compared with pair-fed, sham-operated lean controls but increased the acute thermic response to food and BAT mitochondrial GDP-binding capacity; these effects were inhibited by replacement of HYPX rats with corticosterone. The results suggest that alterations in the hypothalamic pituitary-adrenal axis play a fundamental role in the development and maintenance of genetic obesity. PMID- 3348370 TI - Adaptive changes in individual acyl-CoA esters from hamster BAT during cold acclimation. AB - Long-chain fatty acyl-CoA esters (LCFACoAE) were extracted from freeze-clamped powdered brown adipose tissue (BAT) obtained from thermoneutral control and cold acclimated hamsters and the CoA esters individually separated by high-performance liquid chromatography. LCFACoAE of carbon chain length C12 to C20 were identified by increasing column retention time in the following order: C12:0, C14:1, C14:0, C16:1, C18:2, C16:0, C18:1, C18:0, and C20:4. The mean total LCFACoAE concentrations were 235 +/- 40 nmol/g protein for the control hamsters and 648 +/ 105 nmol/g protein for the 22-day cold-acclimated hamsters. A rapid fourfold increase in the levels of C16:0, C18:0, and C18:1 occurred within hours after initiation of the cold temperature, whereas the concentrations of the other six LCFACoAE either increased only slightly or remained unchanged. Almost 50% of the total LCFACoAE in the BAT of cold-acclimated hamsters was made up of C16:0, C18:0, and C18:1. These results, which demonstrate some dynamic changes in adipose tissue LCFACoAE, are consistent with their proposed role in the initiation and maintenance of BAT thermogenesis. PMID- 3348371 TI - Platelet-activating factor-induced increases in glucose kinetics. AB - Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of [6-3H]- and [U-14C]glucose before and for 4 h after either a bolus injection (300 ng/kg) or a constant infusion (20 or 220 ng.min-1.kg-1) of PAF. The bolus injection of PAF produced a 30% decrease in blood pressure by 5 min that returned to control levels by 30 min. Increased plasma glucose (40%) and lactate (150%) levels after injection of PAF were also transient. In contrast, the bolus injection of PAF elevated the rate of glucose appearance (Ra; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose (28, 150%) and glucose Ra (20, 60%) throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. In a separate group of experiments a complete adrenergic blockade, produced by the constant infusion of propranolol and phentolamine, completely prevented PAF-induced increases in glucose kinetics and the hyperglucagonemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348373 TI - A physical model of the intrathoracic stomach. AB - To determine whether duodenogastric reflux into the thoracic stomach could be caused by the transmission of negative intrapleural pressure fluctuations into the gastric lumen, a physical model is described and an equation calculated Pm + Pa - Pmb - (Sv.Pmb.Vmb/Pm) = Ppl - Sv.Vmb where Pm is intragastric pressure, Pa is atmospheric pressure, Pmb is end-expiratory gastric base pressure, Vmb is corresponding gastric volume, Sv is stiffness of gastric wall, and Ppl is intrapleural pressure. The validity of the model is demonstrated in six anesthetized mongrel dogs (18-31 kg) in which a thoracic stomach was constructed. The transmission of the intrapleural pressure fluctuations across the gastric wall proved to be greatly influenced by the gastric stiffness. The latter parameter varied from 0.05 to 1.97 cmH2O/ml, corresponding with a pressure transmission of 100 and 60%, respectively. Because high degrees of gastric stiffness are only present for large gastric volumes or when gastric peristalsis is present, it is concluded that, in general, the intrapleural pressure fluctuations are transmitted into the thoracic stomach. For this reason, respiratory efforts may play an important role in inducing duodenogastric reflux into the thoracic stomach. PMID- 3348372 TI - Effect of sodium-restricted diet and posture on norepinephrine kinetics in humans. AB - We used compartmental analysis to analyze the kinetics of distribution and metabolism of norepinephrine (NE) and to determine whether the increase in plasma norepinephrine concentration (PNE) during sodium restriction in humans is due to sympathetic nervous system (SNS) activation. [3H]-NE infusion and postinfusion decay were measured in young subjects in the supine position and during 60 min of standing during normal sodium (NS) diet and after 7 days of 10 meq/day sodium restricted (SR) diet. The mean supine PNE was greater during SR diet compared with NS diet (154 +/- 9 vs. 185 +/- 12 pg/ml, P = 0.02, n = 10). During both NS and SR diets, upright PNE increased (163 +/- 4 vs. 359 +/- 38 pg/ml and 182 +/- 8 vs. 401 +/- 26 pg/ml, respectively, multivariate one-way analysis of variance, P less than 0.001, alpha = 0.05). The increases of PNE with both SR diet and upright posture were accompanied by a fall in NE metabolic clearance rate (MCR1). During SR diet this was due to a fall in the volume of distribution of NE (6.1 +/ 0.4 vs. 5.0 +/- 0.4 liters, P = 0.003, n = 10). In contrast to the effect of upright posture to increase NE release into the extra-vascular compartment (NE2), during SR diet there was no change in NE2 (1.63 +/- 0.09 vs. 1.62 +/- 0.1 micrograms.min-1.m-2, P = 0.97, n = 10). Thus the increase in PNE during SR diet in humans can be explained by a fall in the volume of distribution of NE, resulting in a decrease in MCR1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348374 TI - Autoregulation in the developing postnatal intestinal circulation. AB - The relationships among perfusion pressure, blood flow, and oxygen uptake were determined in in vitro ileal loops from 3- and 35-day-old swine. Arterial perfusion of the ileal loops was achieved using a reservoir perfusion apparatus that allowed direct manipulation of perfusion pressure. The hematocrit, partial pressure of oxygen, and partial pressure of carbon dioxide of the blood used to perfuse the gut loops were standardized. During steady-state perfusion at an arterial pressure of 100 mmHg and venous pressure of 0 mmHg, ileal loops from 3 day-old swine demonstrated a higher blood flow (55 vs. 27 ml.min-1.100 g-1, 3 vs. 35 day old) and lower arteriovenous oxygen content difference (3.5 vs. 6.6 ml O2/dl). Oxygen uptake was not statistically different between groups (1.99 vs. 1.76 ml O2.min-1.100 g-1). During perfusion pressure reduction from 150 to 25 mmHg (in successive decrements of 25 mmHg), pressure-flow autoregulation was present in ileal loops from 35-day-old swine but not in ileal loops from 3-day old swine. Similarly, tissue oxygen uptake was more effectively maintained in ileal loops from older swine during perfusion pressure reductions. We speculate that the efficacy of intrinsic regulation of intestinal hemodynamics and oxygenation is dependent, in part, on postnatal age. PMID- 3348375 TI - Motilin receptors on isolated gastric smooth muscle cells. AB - Motilin has a stimulating effect on gastrointestinal motility. The mechanism of its action is not known. Direct and neuronal effects have been postulated. To determine if receptors are present on smooth muscle cells we investigated the effect of synthetic porcine motilin and its interaction with acetylcholine on isolated guinea pig gastric smooth muscle cells. Motilin elicited a dose dependent contraction of gastric smooth muscle cells. Minimal (8.3 +/- 1.3%) and maximal (33.9 +/- 2.4%) responses were observed at 10(-12) and 10(-6) M, respectively. The ED50 of motilin was 10(-9) M. Acetylcholine also elicited a dose-response muscle contraction with a maximal response observed at 10(-7) M. Atropine (10(-7) M) completely inhibited the maximal response to acetylcholine but did not have any effect on the contractile response to motilin. In addition, dibutyryl guanosine 3',5'-cyclic monophosphate (10(-3) M) and substance P antagonist, spantide (10(-4) M), also did not inhibit the action of motilin. Acetylcholine (10(-11) M) shifted the dose-response curve of motilin to the left by 1.5 log units. The maximal response to the combination of motilin (10(-6) M) and acetylcholine (10(-11) M) was 32 +/- 3.2%, which was similar to the maximal response to motilin alone. It is concluded that distinct motilin and muscarinic receptors are present on guinea pig gastric smooth muscle cells. The interaction between motilin and acetylcholine is additive and not potentiative. PMID- 3348377 TI - Comparison of gastrointestinal responses to CCK-8 and associated with vomiting. AB - The gastrointestinal motor and myoelectric responses associated with vomiting induced by apomorphine (APO) and activated by cholecystokinin octapeptide (CCK-8) were compared as well as the mechanisms of initiation of these responses. Twelve dogs were surgically implanted with strain-gauge force transducers or bipolar electrodes for chronic recording of contractile or electrical activity. The responses to CCK-8 were determined in the fasted state and compared with the gastrointestinal motor and myoelectric correlates of vomiting activated by APO. After recording control responses, the effects of the following agents on these responses were determined: atropine, domperidone, and proglumide. In addition, the effects of supradiaphragmatic vagotomy or splanchnicectomy were determined. We found that CCK-8 activated contractile and myoelectric responses in the absence of vomiting, which were similar in most respects to those found in association with vomiting. These responses included 1) the retrograde giant contraction (RGC) and 2) the post-RGC phasic contractions. These RGCs were similar with respect to their activation in an all-or-none fashion, magnitude, duration, and position in the small intestine. The myoelectric correlates of these motor responses were similar qualitatively and quantitatively. The responses activated by APO and CCK-8 differed with respect to their coordination at different levels of the gastrointestinal tract. Whether activated by CCK-8 or APO, atropine blocked the RGC but not the post-RGC contractions. Domperidone blocked all responses to APO but not to CCK-8, and splanchnicectomy did not affect responses to either agent. Vagotomy blocked all gastrointestinal responses to APO but not to CCK-8. These results indicated that CCK-8 activates the gastrointestinal motor and myoelectric correlates of vomiting by a peripheral mechanism that does not include dopamine receptors. PMID- 3348376 TI - Human pancreatic secretion during phase II antral motility of the interdigestive cycle. AB - We determined if changes in the irregular motor activity of phase II, the dominant motility phase in awake fasting humans, are associated with fluctuations in pancreatic secretion by intubating the upper gastrointestinal tract of 15 healthy humans and recording antral and duodenal motility and obtaining duodenal samples for one or two interdigestive motility cycles. Antral phase II activity was graded as having low, intermediate, or high frequency of contractions and related to duodenal trypsin output and plasma concentrations of motilin and human pancreatic polypeptide (HPP), a marker of vagal cholinergic tone. Low, intermediate, and high phase II motor activities were significantly associated with trypsin outputs (U/10 min; mean +/- SE) of 576 +/- 137, 1,441 +/- 225, and 3,621 +/- 521, respectively (P less than 0.001). Plasma motilin levels did not vary with the grades of phase II motility (P greater than 0.1), but levels of plasma HPP and the grades of phase II motility were positively correlated (P less than 0.001). The close correlation among motility, pancreatic secretion, and plasma HPP during phase II suggests that vagal cholinergic pathways are involved in the common regulatory mechanism controlling phase II interdigestive motility and pancreatic secretion. PMID- 3348378 TI - Ammonia production from intraluminal amino acids in canine jejunum. AB - Dietary protein increases the blood ammonia concentration when hepatic metabolic function is impaired, but the site of ammonia production and its specific precursors have not been clearly defined. The purpose of this study is to determine if individual luminal amino acids are metabolized to ammonia by the jejunum during the process of absorption. In anesthetized, fasted dogs, a cannula was inserted into the mesenteric vein draining a segment of the jejunum weighing approximately 18 g, and the ends of the segment were ligated to isolate its blood flow. Ammonia and amino acids were determined in luminal fluid as well as arterial and mesenteric venous blood. One of six amino acids (10 mM) was luminally perfused for a 15-min equilibration period and two 15-min collection periods, and the results were compared with control periods that preceded and followed the amino acid perfusion. Alanine, leucine, and glutamine significantly (P less than 0.01) increased ammonia release into mesenteric venous blood by 37, 42, and 106%, respectively, whereas threonine, serine, and glycine had no effect. Net jejunal uptake of glutamine from arterial blood, which accounts for ammonia release by the jejunum in the basal state, was not altered by perfusions other than with glutamine. Luminal glycine perfusion also caused an increased release of serine into mesenteric venous blood and alanine perfusion increased the release of glutamate. Glutamine perfusion caused increased release of glutamate, alanine, proline, and citrulline. These results indicate that some, but not all, luminal amino acids are partially metabolized to ammonia during the process of absorption in the small intestine. PMID- 3348379 TI - Nature of taurodehydrocholic acid uptake in rat hepatocytes. AB - We studied uptake into isolated rat hepatocytes of the bile acid analogue taurodehydrocholate (TDHC) over a concentration range of 2.5-4,000 microM. Uptake was mainly by a saturable sodium-dependent process with a Km of approximately 50 microM and a Vmax of 0.036 nmol.s-1.mg protein-1. A lesser sodium-independent process was evident but was linear in the range studied. Both processes were inhibited by incubation at 37 degrees C under nitrogen in the presence of 3 mM sodium cyanide or by incubation at 0 degrees C. A single transport site was suggested by the Eadie-Hofstee plot of TDHC uptake from 2.5 to 750 microM. TDHC was a weak competitive inhibitor of taurocholic acid (TCA) uptake (Ki = 236 microM) but was not itself taken up by the TCA transport site. TCA exhibited moderately potent mixed inhibition of TDHC uptake. Uptake of both compounds was strongly inhibited by bromosulfophthalein (BSP) and Rose Bengal, whereas 0.5 mM alanine uptake was not affected. BSP exhibited a complex pattern of inhibition of TDHC uptake: mixed partial inhibition. Degree of inhibition of both TDHC and TCA uptake did not increase as BSP concentrations were increased from 50 to 100 microM. BSP did not exert its inhibitory effects by alteration of membrane potential or sodium gradients; 50 microM BSP changed membrane potential less than 10% and sodium gradient not at all. The data indicate that despite close structural analogy between TDHC and TCA, the two compounds are taken up by different sodium-dependent mechanisms. Nonetheless, the similar qualitative and quantitative effects of BSP on their uptakes suggests the mechanisms are related. PMID- 3348380 TI - Microsphere estimates of blood flow: methodological considerations. AB - The microsphere technique is a standard method for measuring blood flow in experimental animals. Sporadic reports have appeared outlining the limitations of this method. In this study we have systematically assessed the effect of blood withdrawals for reference sampling, microsphere numbers, and anesthesia on blood flow estimates using radioactive microspheres in dogs. Experiments were performed on 18 conscious and 12 anesthetized dogs. Four blood flow estimates were performed over 120 min using 1 X 10(6) microspheres (15 microns) each time. The effects of excessive numbers of microspheres (13 million), pentobarbital sodium anesthesia (30 mg/kg), and replacement of volume loss for reference samples with dextran 70 were assessed. In both conscious and anesthetized dogs a progressive decrease in gastric mucosal blood flow and cardiac output was observed over 120 min. This was also observed in the pancreas in conscious dogs. The major factor responsible for these changes was the volume loss due to reference sample withdrawals. Replacement of the withdrawn blood with dextran 70 led to stable blood flows to all organs. The injection of excessive numbers of microspheres did not modify hemodynamics to a greater extent than did the injection of 4 million microspheres. Anesthesia exerted no influence on blood flow other than raising coronary flow. We conclude that although blood flow to the gastric mucosa and the pancreas is sensitive to the minor hemodynamic changes associated with the microsphere technique, replacement of volume loss for reference samples ensures stable blood flow to all organs over a 120-min period. PMID- 3348381 TI - Interaction of theophylline, verapamil, and diltiazem on hamster diaphragm muscle force in vitro. AB - The effect of the calcium channel blocker verapamil (5 microM) or diltiazem (5 microM) on force production and resting membrane potential (Em) was studied in the hamster diaphragm muscle. The calcium channel blockers decreased force at high frequencies of stimulation and decreased Em by 3 +/- 1 mV. The interaction of theophylline and the calcium channel blockers was also studied. When given simultaneously, the calcium channel blockers prevented the increase in force at high frequencies with theophylline at 1 mM and at all frequencies with theophylline at 0.55 mM. There was no change in Em when theophylline and calcium channel blockers were given together. Similar results were obtained by removing external calcium. The decrease in force produced by verapamil was not reversed by subsequent addition of theophylline. Theophylline did reverse the decrease in force produced by diltiazem. Verapamil reversed the increase in force at high frequencies produced by theophylline. Diltiazem reversed the force increase at low frequencies as well. These studies suggest that extracellular calcium is important in skeletal muscle contractility especially at high frequencies. Extracellular calcium is also important for the potentiation of force and the hyperpolarization of the Em produced by theophylline. The mechanism by which extracellular calcium contributes to these actions of theophylline is not known. PMID- 3348382 TI - Bicarbonate secretion in rat distal colon in vitro: a measurement technique. AB - To study HCO3- secretion in rat distal colon, we utilized a technique that permits control of electrical and chemical transepithelial gradients. With symmetrical solutions (pH 7.4, [HCO3-] 25 mM, and CO2 tension 40 mmHg) bathing both tissue surfaces and under short-circuit conditions, HCO3- secretion remained stable for greater than 4 h at 1 mueq. h-1.cm-2. As the mucosal solution was alkalinized, the serosal solution was acidified at 3.1 mueq.h-1.cm-2. Ninety-four percent of serosal acidification was accounted for by the rate of metabolic lactic acid generation and transepithelial HCO3- secretion. Clamping transepithelial voltage reversibly affected net HCO3- secretion, and a linear relationship existed between clamped mucosal voltage and net HCO3- flux (r = 0.99); mucosal voltage of -68 mV completely inhibited net secretion. The apparent permeability coefficient of the colon to HCO3- is 2.8 X 10(-6) cm/s. One millimolar ouabain completely inhibited net HCO3- secretion. Acetazolamide (10( 4) M) inhibited secretion by approximately 50%, whereas a 10(-3) M concentration inhibited secretion by 90%. These data demonstrate that net colonic HCO3- secretion can be measured without imposed electrical and chemical gradients and that this flux is voltage sensitive and depends on carbonic anhydrase and Na+-K+ ATPase activities. PMID- 3348383 TI - Cl(-)-HCO3- exchange is present with Na+-K+-Cl- cotransport in rabbit parotid acinar basolateral membranes. AB - The presence of a sodium-independent electroneutral Cl(-)-anion exchanger in a basolateral membrane vesicle preparation from the rabbit parotid is demonstrated. This exchanger is shared by HCO3-, NO3-, Br-, F-, and formate, but not by thiocyanate, acetate, methylsulfate, gluconate, or hydroxyl ions. In order of relative potency, the exchanger is inhibited by SITS greater than or equal to phloretin greater than furosemide greater than bumetanide greater than or equal to phlorizin. A Na+-K+-dependent component of chloride flux, presumably due to the Na+-K+-Cl- cotransporter already characterized in this preparation, was also observed. 36Cl uptake into vesicles loaded with KCl exhibited an "overshoot" of intravesicular [36Cl] due to 36Cl-Cl exchange. However, when vesicles were loaded with both KCl and NaCl the height of the overshoot was considerably decreased indicating a Na+-K+-dependent dissipation of the intravesicular to extravesicular chloride gradient. This experiment provides strong evidence that the Na+-K+-Cl- cotransporter and the Cl(-)-HCO3- exchanger are present in the same membrane vesicles. These results indicate that Cl(-)-HCO3- exchange is present in the basolateral membrane of parotid acinar cells and thus that this transporter may play a significant role in salivary secretion. PMID- 3348384 TI - Spatial heterogeneity of metabolism in skeletal muscle in vivo studied by 31P-NMR spectroscopy. AB - Phase-modulated rotating-frame imaging, a localization technique for phosphorus nuclear magnetic resonance spectroscopy, has been applied to obtain information on heterogeneity of phosphorus-containing metabolites in skeletal muscle of the rat in vivo. The distal muscles of the rat hindlimb have been studied at rest and during steady-state isometric twitch contraction; the use of a transmitter surface coil and an electrically isolated, orthogonal receiver Helmholtz coil ensure accurate spatial assignment (1 mm resolution). At rest, intracellular pH was higher and PCr/(PCr + Pi) was lower in deeper muscles compared with superficial muscle of the distal hindlimb. Upon steady-state stimulation, the relatively more alkaline pH of deep muscle was maintained, whereas greater changes in PCr/(PCr + Pi) and Pi/ATP occurred in the superficial muscle layer. This method allows rapid (75 min for each spectral image) acquisition of quantitative information on metabolic heterogeneity in vivo. PMID- 3348386 TI - Dissociation of osmotic and ionic modulation of aldosterone secretion. AB - Although other investigators have suggested that reductions in either Na or chloride concentration stimulate aldosterone secretion, we previously found that small reductions in NaCl (3-7 mM) that enhanced angiotensin II-(ANG II) and [K]- but not adrenocorticotropic hormone (ACTH)-stimulated aldosterone secretion are due to a change in osmolality. In the present study, aldosterone secretion by an isolated perfused canine adrenal gland was stimulated by low doses of ANG II or ACTH or by small increases in perfusate [K], and during this stimulation, replacing 25 mM NaCl with an isosmotic amount of mannitol enhanced aldosterone secretion induced by each of the above secretagogues. Choline chloride significantly enhanced ANG II-stimulated aldosterone secretion when used in place of 25 mM NaCl, but sodium methylsulfate did not. Large isosmotic reductions in [NaCl] failed to alter ACTH-stimulated cortisol secretion or the conversion of either exogenous corticosterone or 11-deoxycorticosterone to aldosterone. Thus, reductions in Na, but not in chloride concentration, specifically enhance the ability of the adrenal glomerulosa to secrete aldosterone in response to ANG II, K, and ACTH by an action on some site in the steroidogenic cascade that is sensitive to ANG II, potassium, and ACTH. PMID- 3348385 TI - Lectin-gold labeling of glycoconjugates in normal and Brattleboro rat papilla: effect of vasopressin. AB - Some reports suggest that the plasma membrane glycocalyx of collecting duct epithelial cells, as well as interstitial glycoconjugates, may be involved in vasopressin action and urinary concentration. In view of this, we have used the lectin-gold technique to map and quantify Helix pomatia lectin (HPL)-binding sites in the inner medulla of kidneys from normal Long-Evans rats, vasopressin deficient Brattleboro rats, and Brattleboro rats treated for up to 5 wk with exogenous vasopressin. The results show that the labeling of epithelial cell plasma membranes from collecting ducts and thin limbs of Henle is not different between normal and Brattleboro rats, and the labeling is not modified by chronic vasopressin treatment. In contrast, the heavy interstitial labeling seen in normal rats is virtually absent from Brattleboro rats, but it is progressively restored by chronic vasopressin treatment of Brattleboro rats. These results show that vasopressin does not modify HPL-binding glycoconjugates on epithelial cell plasma membranes, but that vasopressin treatment has a major effect on HPL binding glycoconjugates in the medullary interstitium. PMID- 3348387 TI - Parathyroid hormone-independent regulation of 1,25(OH)2D in response to inhibition of bone resorption. AB - Both plasma level of 1,25-dihydroxyvitamin D [1,25(OH)2D] and intestinal Ca absorption increase after biphosphonate-induced inhibition of bone resorption. Parathyroid hormone (PTH) has been considered a key mediating element of this homeostatic response. In the present work, the role of PTH was assessed by studying the influence of 1-hydroxypentane-1,1-bisphosphonate (HPeBP) on vitamin D and Ca metabolism in both intact and thyroparathyroidectomized (TPTX) rats. In intact rats, HPeBP given at 0.1 mg P/kg body wt sc for 10 days strongly inhibited bone resorption without affecting bone formation. This effect was associated with a marked stimulation of intestinal Ca absorption and Ca balance. In this condition, HPeBP caused a marked rise in plasma 1.25(OH)2D without affecting the level of 25-hydroxyvitamin D. In TPTX rats, HPeBP given at same dose also inhibited bone resorption and enhanced plasma 1,25(OH)2D, intestinal Ca absorption and Ca balance. In summary, this study shows that bisphosphonates such as HPeBP with prevailing inhibitory activity on bone resorption induce a marked stimulation of both 1,25(OH)2D production and intestinal Ca absorption. This homeostatic response is not attenuated after PTH removal. Thus, as previously shown for the response to low Ca diet, PTH does not appear to be an essential mediating factor for stimulating 1,25(OH)2D production in response to an increase in bone mineral retention. PMID- 3348388 TI - Opposite effects of 1,25(OH)2D3 on synthesis and release of PTH compared with secretory protein I. AB - Aggregates of bovine parathyroid cells (organoids) were cultured with or without 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and examined for effects on the synthesis, cellular content, and release of parathyroid hormone (PTH) and secretory protein I. Organoids cultured with 120 pM 1,25(OH)2D3 at 1.35 mM calcium contained 27 +/- 2% (mean +/- SE) less and released 26 +/- 7% less PTH and contained 21 +/- 2% more and released 49 +/- 16% more secretory protein I than untreated organoids. After 15-min incubations with radioactive leucine, treated organoids incorporated 25 +/- 2% less radioactivity into precipitable cellular proteins than did untreated organoids, indicating that the overall synthetic rate of proteins was decreased by 1,25(OH)2D3 at 1.35 mM calcium. After separation of cellular proteins by gel electrophoresis, analysis of individual protein bands indicated that the mean treated-control ratio for proparathyroid hormone radioactivity was 0.88 +/- 0.06 (P less than 0.10) while that for secretory protein I was 1.56 +/- 0.17 (P less than 0.01), respectively. Experiments were performed at 1.2, 12, 120, and 1,200 pM 1,25(OH)2D3 and both 1.4 and 1.8 mM calcium. In both cases, increasing levels of 1,25(OH)2D3 progressively decreased PTH synthesis and release and progressively increased that of secretory protein I, significant effects being observed at 1.2 pM 1,25(OH)2D3. We conclude that at physiological calcium levels, 1.2-1,200 pM 1,25(OH)2D3 suppresses the synthesis and secretion of PTH, increases that of secretory protein I, and at similar concentrations decreases the overall protein synthetic rate compared with untreated controls. PMID- 3348389 TI - Free and total catecholamines in critical illness. AB - The magnitude of circulating free and total (free plus conjugated) catecholamine responses to a strong and sustained stimulus was investigated in four groups of patients: traumatic brain injury (n = 24), vascular brain injury (n = 10), polysystem trauma (n = 7) and medical/surgical patients in an intensive care unit (n = 29). Despite significant three- to sevenfold elevations in both free and total norepinephrine (NE) and epinephrine (E), the ratio of free to total NE and E remained constant over a very broad range of values. The proportion of free E was twice normal (30.1-33.5 vs. 16.2%) in all but patients with polytrauma, whereas the percentage of free NE was unchanged in all patients (43.0%). All dopamine (DA) parameters remained generally normal. In the patients with traumatic or vascular brain injury, significant inverse correlations were present between the degree of neurological dysfunction, as indicated by the concomitant Glasgow coma score, and free NE, E, and DA and total NE and DA levels. Thus, during conditions of intense and prolonged catecholamine release, the proportion of free catecholamine remains constant and the total as well as free catecholamine concentration is proportional to the Glasgow coma score. PMID- 3348390 TI - Comparison of [14C]glucose and [14C]deoxyglucose as tracers of brain glucose use. AB - Because glucose metabolism and functional activity in brain regions are normally coupled, knowledge of regional brain glucose use can yield insights into regional functional activity. The deoxyglucose (DG) method is widely used for this purpose in experimental animals and humans but questions have arisen regarding its limits and accuracy. Therefore an experiment was designed to compare the DG method on a structure-by-structure basis with another tracer of glucose use, [6-14C]glucose, in normal rats. The cerebral metabolic rates obtained using the two tracers were similar in the telencephalon, but the results using DG were substantially lower in the midbrain and hindbrain (diencephalon, 18%; mesencephalon, 20%; metencephalon, 29%; and myelencephalon, 35%). The primary DG metabolite, DG 6 phosphate (DG-6-P) was found to disappear in a non-uniform manner from the major brain structures: telencephalon less than diencephalon less than mesencephalon = metencephalon less than myelencephalon. Thus a correlation was found between the rate of DG-6-P loss and the extent to which the DG method gave lower values of glucose use. Thus this may explain, at least in part, the discrepancies between the two methods. PMID- 3348391 TI - Disappearance of growth hormone from plasma of fetal and newborn sheep. AB - The disappearance of growth hormone (GH) from plasma was measured after a single intravenous injection in fetal and newborn sheep and fetal sheep after simulated birth in utero. The process was adequately described when separated into two exponential components, consistent with an inner (plasma) and outer (composite tissue) pool. Plasma clearance rate increased from 3.4 +/- 0.2 (SE, n = 6) in fetuses to 3.9 +/- 0.1 (n = 5) ml.min-1.kg-1 in newborns (P less than 0.05), but was not altered significantly after simulated delivery in utero. The volume of distribution decreased from 74 +/- 4 ml/kg before birth to 47 +/- 2 ml after natural birth (P less than 0.001). The basal secretory rate decreased from 2.4 +/ 0.2 before birth to 0.27 +/- 0.02 microgram/min after birth (P less than 0.001) and to a lesser extent after simulated delivery. The rate constant for irreversible loss, Kd, increased from 0.052 +/- 0.004 min-1 before birth to 0.093 +/- 0.002 min-1 after birth (P less than 0.001). Because plasma GH concentration in steady state equals secretory rate/(volume of distribution X Kd), one may calculate that 83% of the total decrease in GH, which occurs after birth, can be explained by diminished secretory rate, whereas 17% can be explained by more rapid loss from the plasma. PMID- 3348392 TI - Ontogeny of thyroid hormone effect on tissue 5'-monodeiodinase activity in fetal sheep. AB - Most of the thyroxine (T4) in fetal mammals is deiodinated to the inactive metabolite, reverse triiodothyronine (rT3), via an iodothyronine 5-monodeiodinase in fetal tissues. Maturation of the tissue 5'-monodeiodinase (MDI) enzymes required for conversion of T4 to active triiodothyronine (T3) in the rat, an altricial species, occurs in the postnatal period. To characterize fetal maturation of the enzymes for active T3 production in a precocial species, 5'-MDI activities were measured in liver, kidney, and brain tissue homogenates of ovine fetuses 13 days after total thyroidectomy (Tx) conducted at gestational ages of 99-107 or 129-132 days. Sham-operated twin fetuses served as controls. Hepatic type I 5'-MDI activity was not significantly lowered by Tx in group I but was significantly lower after Tx in group II fetuses. Renal type I 5'-MDI was not affected by Tx in either group. Type II 5'-MDI activity in cerebral cortex was significantly elevated after Tx in both groups I and II fetuses. Tissue sulfhydryl contents were similar in liver, kidney, and cerebral cortex from control and Tx fetuses in group I. These data indicate that hypothyroidism induced early in the third trimester is associated with increased brain type II 5'-MDI activity without significant change in liver or kidney type I 5'-MDI. Late third trimester hypothyroidism is associated with decreased type I 5'-MDI activity in liver homogenates as well as increased type II 5'-MDI activity in brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348393 TI - Increased in vivo glucose utilization in 30-day-old obese Zucker rat: role of white adipose tissue. AB - In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by [3-3H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia (140 vs. 55 microU/ml). In obese compared with lean rats, tissue glucose uptake (assessed by the 2-deoxyglucose technique) was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart, in proximal intestine, and in total muscular mass of limbs. Our data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake. PMID- 3348394 TI - Mitochondrial membrane transitions in heart and other organs of a hibernator. AB - Critical temperatures (T) for transitions in both lipid structure and enzyme function of mitochondrial membranes from liver, kidney, brown fat, and heart tissues were determined for the hibernator Spermophilus lateralis at two weekly intervals from early summer to late autumn and during hibernation. For all tissues T fell into one of three groups: those below 4 degrees C (the minimal level of accurate determination), those centered about a mean of 11.9 +/- 1.4 degrees C, and those centered about a mean of 20.9 +/- 1.8 degrees C. The T for tissues from torpid animals and from heart, at all sampling periods, was below 4 degrees C. For liver, kidney, and brown fat the mean T was approximately 21 degrees C in early summer but was lowered later in the season in a two-step process, falling to below 4 degrees C before the animals were exposed to cold and entering torpor. It is concluded that for mitochondria the thermal response of the membrane lipids is altered such that the transition in structure and function is always below the minimum body temperature likely to be experienced by this animal. Heart tissue is exceptional in that the transition is at a temperature consistent with a body temperature of torpor even in summer-active animals. PMID- 3348395 TI - Bovine gallbladder muscularis: source of a myogenic receptor for cholecystokinin. AB - Despite being a classic target for the gastrointestinal peptide hormone, cholecystokinin (CCK), the gallbladder CCK receptor is not well characterized. Pharmacological studies of small species suggest that CCK action can be mediated by direct myogenic or by both myogenic and neurogenic receptors. To prepare for the biochemical characterization of a gallbladder CCK receptor and to define the subtype of the receptor being studied, we have performed autoradiographic localization and pharmacological characterization of CCK receptors on bovine gallbladder. Autoradiography demonstrated high-affinity specific CCK-binding sites only on the muscularis. CCK-8 stimulated tonic contraction of longitudinal strips of gallbladder muscularis in a concentration-dependent manner, with an ED50 of 0.2 nM. Antagonism at the cholinergic receptor with 1 microM atropine or axonal transmission with 1 microM tetrodotoxin did not modify CCK-induced contraction, supporting a direct myogenic effect of this hormone. Optimal electrical field stimulation (10 V, 10 Hz, 500 microseconds) to elicit a neuronal response resulted in muscle strip relaxation, which was abolished with adrenergic blockade (1 microM phentolamine, 1 microM propranolol). Although acetylcholine administration stimulated contraction, electrical field stimulation did not, even in the presence of phentolamine, propranolol, and/or CCK. Thus, in bovine gallbladder muscularis, there is evidence for a functional CCK receptor only on smooth muscle cells. Demonstration of a single, high-affinity specific CCK binding site on an enriched plasma membrane preparation of bovine gallbladder muscularis is consistent with this representing a myogenic CCK receptor. PMID- 3348396 TI - Stimulation of rabbit lacrimal gland secretion with biologically active peptides. AB - To determine whether biologically active peptides can stimulate lacrimal gland secretion, we measured fluid and protein secretion from the cannulated lacrimal gland excretory duct of anesthetized rabbits after arterial injection of various peptides. Vasoactive intestinal peptide (VIP, 0.003-3 nmol) and porcine histidine isoleucine-containing peptide (PHI, 0.01-3 nmol) stimulated fluid and protein secretion in a dose-dependent manner. Cholecystokinin octapeptide (CCK-8, 0.01-3 nmol) stimulated fluid but not protein secretion. Neither bombesin nor eledoisin in doses as high as 3 nmol stimulated fluid or protein secretion. When combinations of high or low doses of VIP and the cholinergic agonist acetylcholine (ACh) were injected simultaneously, fluid and protein secretion was additive. We concluded that VIP and PHI stimulated secretion of lacrimal gland fluid and protein, CCK-8 stimulated secretion of fluid, and bombesin and eledoisin did not stimulate either fluid or protein secretion. VIP and ACh, both found in lacrimal gland nerve endings, stimulate lacrimal gland fluid and protein secretion by separate pathways. PMID- 3348397 TI - Intestinal anaphylaxis: rapid changes in mucosal ion transport and morphology. AB - Anaphylactic reactions can be elicited by beta-lactoglobulin (beta LG) in the isolated colonic and ileal mucosae of guinea pigs fed cow milk. We have shown that these tissues respond to antigen challenge with a rapid rise in short circuit current (SCC) due to net chloride secretion in the colon and less well characterized ion movements in the ileum. Here, tissues were characterized morphologically at or near the peak of the SCC response 2 min after antigen addition. These sensitized preparations, or naive tissues passively sensitized with immune sera and challenged with beta LG, showed numerous structural alterations that correlated significantly with the change in SCC. In the ileum, these changes included compound exocytosis of mucous granules from goblet cells of crypts but not of villi and a decrease in the intercellular space of the crypts. In contrast, colonic goblet cells of both crypts and luminal surface showed no evidence of secretion, but crypt architecture was reproducibly and characteristically altered. Thus antigen challenge of intestinal mucosa results in temporally related but diverse changes in morphology and ion transport. PMID- 3348398 TI - Thyroxine effect on exocrine pancreatic development in rats. AB - Thyroxine and glucocorticoids both play important roles in regulating the development of mammalian tissues. The mechanisms by which they modulate the developmental process is not fully understood. Furthermore, the interaction between the effects of two hormones on the pancreas has not been studied in detail. To investigate these issues, we studied the effect of thyroxine and/or corticosterone on the development of the exocrine pancreas in normal and adrenalectomized rats. Daily injection of thyroxine (0.1 micrograms/g body wt) to pups starting at day 5 of age resulted in precocious increases of exocrine enzymes in the pancreata of these pups. Hypothyroid pups, induced by propylthiouracil, exhibited suppression of development of their pancreatic exocrine enzymes. Replacement of thyroxine or corticosterone alleviated the suppression of exocrine enzyme development in these pups. Rat pups, who underwent adrenalectomy at 5 days of age, had undetectable plasma corticosterone and exhibited similar suppression of pancreatic enzyme development. Injection of thyroxine or corticosterone alone to adrenalectomized pups led to normal development of exocrine pancreatic enzymes. When both thyroxine and corticosterone were given together to adrenalectomized pups, their pancreatic enzyme levels were found to increase to values above those of pups treated with thyroxine or corticosterone alone. We conclude that thyroxine has both direct and indirect modulatory roles in the development of the rat exocrine pancreas. Normal development of the exocrine pancreas depends on both intact adrenal and thyroid function in the rat. PMID- 3348399 TI - Taurine transport by rat intestine. AB - Rat intestinal transport of taurine was studied using jejunal brushborder membrane vesicles and everted jejunal sacs. Membrane vesicle experiments showed that the initial rate (at 10 s) of 10 microM taurine uptake was stimulated 3.5 fold by an inwardly directed Na+ gradient when compared with a K+ gradient. The Cl- salt of Na+ supported uptake to a significantly greater degree than did more (SCN-) or less (SO2-4) permeant salts. Na+-stimulated uptake at 1 min achieved a value 2.5 times greater than equilibrium ("overshoot"). When 10 s taurine uptake was determined over a range of taurine concentrations (10-1,000 microM) and plotted using the Woolf-Hofstee equation, a diffusive and carrier-mediated component was apparent. Half-maximal, carrier-mediated uptake occurred at 25 +/- 9 microM taurine (Km). An inside-negative, valinomycin-induced K+ diffusion potential stimulated 10-s taurine uptake when compared with voltage-clamped conditions (4.9 vs. 2.6 pmol/mg protein; P less than 0.05). Incubation with a structural analogue, hypotaurine, reduced 10-s taurine uptake by 89%. Uptake by everted jejunal sacs also demonstrated Na+ stimulation and inhibition by hypotaurine. These data confirm the existence of a high-affinity rat jejunal brush-border membrane-associated taurine transport mechanism that is electrogenic, stimulated by a Na+ gradient, and modified by external Cl-. PMID- 3348400 TI - Intestinal capillary filtration in acute and chronic portal hypertension. AB - The impact of acute and chronic portal hypertension on the dynamics of intestinal microvascular fluid exchange was examined in anesthetized, fasted, sham-operated control rats with normal portal pressures (CON), during acute elevations in portal pressure (APH) in control rats, and in rats in which chronic portal hypertension (CPH) was produced by calibrated stenosis of the portal vein 10 days prior to the experiments. Although intestinal blood flow and vascular resistance were not altered by APH in control rats, CPH was associated with an increased intestinal blood flow and reduced intestinal vascular resistance when compared with CON and APH. Intestinal capillary pressure and lymph flow were elevated in APH and CPH relative to control values. However, the increase in both variables was greater in CPH. The capillary filtration coefficient was elevated only in CPH. The transcapillary oncotic pressure gradient was not altered by APH or CPH. Interstitial fluid pressure was increased from -1.1 mmHg in CON to 3.9 mmHg during APH and to 5.0 mmHg in CPH. The results of this study indicate that chronic elevations in portal venous pressure produce larger increments in intestinal capillary pressure and filtration rate than do acute elevations in portal venous pressure of the same magnitude. However, the potential edemagenic effects of elevated capillary pressure in both acute and chronic portal hypertension are opposed by increases in lymph flow and interstitial fluid pressure. PMID- 3348402 TI - Differentiation of rat small intestinal epithelial cells by extracellular matrix. AB - The role of extracellular matrix as a determinant of intestinal cell maturation was explored by growing a normal, but immature, rat small intestinal cell line (IEC-6) on basement membrane extract from Engelbreth-Holm-Swarm (EHS) sarcoma cells (ECM). Grown on plastic or glass, these cells are relatively immature and proliferate rapidly. In contrast, cells on ECM attached more rapidly, stopped proliferating, and rapidly organized into multicellular complex structures. Ultrastructurally, cells grown on ECM displayed significantly more mitochondria, rough endoplasmic reticulum, apical microvilli, and complex golgi apparatus, consistent with greater maturity and synthetic activity. By indirect immunofluorescence, sucrase, alkaline phosphatase, and cellular apolipoprotein B were present in cells grown on ECM only. In contrast to cells grown on glass, these cells also demonstrated Na-dependent glucose absorption, a function unique to mature villus cells (7). We conclude that the basement membrane may be a key determinant of intestinal epithelial cell maturation. The development of a mature villuslike intestinal cell in vitro may have wide application for future studies of induction and regulation of intestinal maturation and function. PMID- 3348401 TI - Triton WR-1339-induced changes in serum lipids and biliary lipid secretion. AB - Biliary lipid secretion rates were measured in fed rats after an intravenous injection of Triton WR-1339 (TWR, 60 mg/100 g body wt), an agent that inhibits lipoprotein removal from the circulation. Serum triglyceride, phospholipid (PL), and cholesterol (CH) concentrations rose within 3 h of TWR to 45, 6.6, and 10 times control values, respectively, at 24-36 h. Serum lipids fell rapidly at 48 h and were normal by 72-96 h after TWR. TWR did not alter bile flow, hepatic bile acid transport, or biliary bile acid output. Within 0.5 h of TWR, biliary PL and CH outputs fell greater than 70%, and taurocholate-stimulated biliary PL secretion was markedly reduced. Biliary PL and CH secretion rates were approximately 30 and approximately 40% suppressed, respectively, 24 h after TWR, 160 and 330% elevated, respectively, at 48 h, and normally by 72 h, despite normal taurocholate-stimulated biliary PL secretion. Biliary beta-glucuronidase secretion (a lysosomal enzyme) was unchanged for 3 h after TWR but was increased at 24, 48, and 72 h, independent of biliary lipid secretion. Thus TWR acutely dissociates bile acid from lipid secretion without impairing bile acid transport or biliary lysosomal discharge. Late changes in biliary lipid secretion relate closely to TWR-induced change in serum lipid metabolism but not to stimulation of biliary lysosomal discharge. PMID- 3348403 TI - Effect of bombesin and gastrin-releasing peptide on canine sphincter of Oddi. AB - This study reports the effects of bombesin and gastrin-releasing peptide (GRP) on the canine sphincter of Oddi using a method that allows repeated cannulation of the biliary sphincter in the unanesthetized animal through a Thomas cannula placed opposite the biliary papilla. Immediately after intravenous administration of bombesin or GRP, phasic sphincter contractions disappeared, basal sphincter pressures fell, and common bile duct pressures rose. Because bombesin releases cholecystokinin (CCK) and CCK resulted in a similar pattern to that of bombesin, the bombesin effect on the sphincter of Oddi may have been secondary to CCK's effect on the sphincter. To test if the bombesin effect on the sphincter of Oddi was due to the release of CCK, we blocked CCK release by administration of somatostatin, having first established that somatostatin blocked endogenous CCK release in our animal model by use of an intraduodenal infusion of lipid. Exogenous administration of bombesin failed to alter sphincter of Oddi or common bile duct pressures in dogs treated with somatostatin. Somatostatin did not, however, block CCK's effect on gallbladder contraction, since exogenous administration of CCK after somatostatin injection resulted in the pressure changes in the biliary tree typical of CCK-induced gallbladder contraction. Thus bombesin administration appears to result in sphincter relaxation and gallbladder contraction by the release of endogenous CCK rather than by a direct effect. The increase in common bile duct pressures was due to gallbladder contraction, since this rise in pressure was abolished by cholecystectomy. The peptide effect on sphincter contraction and basal sphincter pressure were unaffected by cholecystectomy. PMID- 3348404 TI - Gradual reintroduction of oxygen reduces reperfusion injury in cat stomach. AB - Recent studies have shown that oxygen-derived free radicals are responsible for a major portion of ischemia-reperfusion injury in the stomach. The oxygen radicals are produced during reperfusion when oxygen delivery to the tissue increases. In the present study we investigate the effect on mucosal injury of regulating the rate of reintroduction of oxygen to the stomach after ischemia. Local gastric ischemia was achieved by reducing celiac artery pressure to 30 mm Hg for 1 h. Ischemic injury was assessed by measuring the loss of 51Cr-labeled red blood cells across the gastric mucosa. Mucosal blood loss was negligible before and during the ischemia period but increased to 0.178 ml.min.-1.100 g-1 during reperfusion. When blood flow to the stomach was gradually returned to normal after ischemia by increasing celiac artery pressure by 10 mmHg every 10 min, the mucosal blood loss was reduced to 0.013 ml.min.-1.100 g-1. If the stomach was vascularly perfused with low PO2 (34 mmHg) blood for 1 h after ischemia before being returned to normal arterial perfusion, the mucosal blood loss was also reduced to 0.063 ml.min.-1.100 g-1. When the stomach was made hypoxemic for 1 h rather than ischemic by perfusing the vasculature with low PO2 (29 mmHg) blood then reperfused with normoxic blood, there was very little mucosal bleeding (0.014 ml.min.-1.100 g-1). The data indicate that gastric mucosal bleeding after ischemia is reduced if the tissue is returned slowly to a normal PO2. These findings support the concept that reperfusion injury is due largely to the production of oxygen radicals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348405 TI - Lymphatic pathways and role of valves in lymph propulsion from small intestine. AB - The pathways through which lymph is propelled from the mucosal, submucosal, and muscle layer lymphatics of the small intestine, the interconnections between these layers, and the location of lymphatic valves within these layers were studied. Injections of fluid into a single lacteal or submucosal lymphatic of rats, rabbits, dogs, and cats spread in all directions through the submucosal lymphatics and into laceteals but did not enter the lymphatics of the muscle layer. Injections into muscle layer lymphatics also spread in all directions but in no case entered the submucosal lymphatics. The submucosal and muscle layer lymphatics join within the bowel wall near the mesenteric border to form collecting lymphatics characterized by valves and spontaneous contractions. These data indicate that lymphatics of the mucosa and submucosa form a syncytium independent of the muscle layer lymphatics and that few if any valves exist within these lymphatic networks. Cycling lacteal pressures were measured when intestinal motility was present but not when motility was abolished, suggesting that intestinal motility might have a role in lymph propulsion. PMID- 3348406 TI - Amiloride inhibits rat mucosal ornithine decarboxylase activity and DNA synthesis. AB - Refeeding fasted rats induces a dramatic trophic response in gastrointestinal mucosa and is associated with elevations in both the rate of DNA synthesis and ornithine decarboxylase (ODC) activity. The signal for these increases is unknown. Amiloride prevents cell alkalinization by blocking Na+-H+ exchange at apical epithelial cell membranes. In study 1, rats were fasted 48 h, treated with amiloride (0.5 to 500 mg/kg), and refed for 4 h. Refeeding increased ODC activities in the jejunal mucosa (X8) and liver (X19) but not in the oxyntic gland mucosa. In the jejunum, but not the liver, the activation of ODC was completely abolished by 100 mg/kg amiloride. In study 2, the rate of DNA synthesis was determined by measuring the rate of [3H]thymidine incorporation 16 h after refeeding. Refeeding resulted in significantly increased rates of DNA synthesis (dpm.microgram DNA-1.30 min-1) over fasted levels, and amiloride at 100 mg/kg significantly reduced the elevations in the jejunum and liver. In conclusion, amiloride inhibits the postprandial increases in jejunal ODC activity and DNA synthesis in the jejunum and liver. The results indicate that 1) the Na+ H+ antiport is essential to the increased ODC activity in the jejunum and the stimulation of DNA synthesis in the jejunum and liver after a meal and 2) increases in DNA synthesis and their suppression by amiloride are not necessarily linked to ODC activity. PMID- 3348407 TI - Cephalic phase response of pancreatic exocrine secretion in conscious dogs. AB - The effects of three taste solutions on the cephalic phase of pancreatic secretion were studied in conscious dogs. Male beagle dogs weighing 9-11 kg were prepared with gastric and duodenal fistulas. Gustatory receptors were stimulated for 5 min with 100 ml of 0.5% agar solutions containing 0.05, 0.12, and 0.3 M of either sodium chloride, sucrose, or monosodium glutamate (MSG). Pancreatic juice was collected every 5 min before and after stimulation, and volume flow and protein output were measured. Pancreatic secretory responses were found to vary with the type of taste stimulus. Sucrose was a better stimulus than MSG for both protein output and volume flow. Taste stimulation with sodium chloride produced a lower pancreatic response than those with sucrose or MSG. PMID- 3348408 TI - Specific receptors for epidermal growth factor in rat intestinal microvillus membranes. AB - Epidermal growth factor (EGF) is present in high concentrations in milk, salivary, and pancreaticobiliary secretions. EGF, delivered to the intestinal lumen by these fluids, appears to influence intestinal proliferation. Because EGF exerts its mitogenic effect through binding to specific membrane-bound receptors, binding studies of 125I-labeled EGF to purified microvillus membrane (MVM) preparations from fetal, newborn, and adult rat small intestine were performed. Using the membrane filter technique, binding of 125I-EGF to adult MVM was specific, saturable, and reversible. Adult and fetal MVM binding was rapid and reached a plateau after 30 min at both 20 and 37 degrees C. No binding was detected at 4 degrees C. Specific binding increased linearly from 0 to 75 micrograms MVM protein. Scatchard analysis revealed a single class of receptors in fetal and adult MVM with an association constant of 1.0 +/- 0.35 X 10(9) and 2.3 +/- 1.6 X 10(9) M-1, respectively. Binding capacity was 435.0 +/- 89 and 97.7 +/- 41.3 fmol 125I-EGF bound/mg MVM protein for fetal and adult MVM, respectively. Newborn MVM binding was negligible. After binding, cross-linking utilizing disuccinimidyl suberate, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography revealed a 170-kDa receptor. These data demonstrate specific receptors for EGF on MVM of rat small intestine and, thus, suggest a mechanism for the intraluminal regulation of enterocyte proliferation by EGF. PMID- 3348409 TI - Pancreatic bicarbonate response to HCl before and after cutting the extrinsic nerves of the pancreas in dogs. AB - In two sets of dogs with gastric and pancreatic fistulas, we studied the effect of atropine on pancreatic bicarbonate output and release of secretin in response to intraduodenal HCl before and after stepwise removal of the extrinsic nerves of the pancreas, i.e., celiac and superior mesenteric ganglionectomy alone or truncal vagotomy alone and truncal vagotomy plus celiac and superior mesenteric ganglionectomy. Ganglionectomy alone did not alter the incremental bicarbonate response to HCl. Truncal vagotomy alone significantly (P less than 0.05) decreased the incremental bicarbonate response to low (1.5 and 3 mmol/h) but not high (6 to 24 mmol/h) loads of HCl. Additional ganglionectomy restored the bicarbonate response to prevagotomy levels. With the extrinsic nerves intact and after ganglionectomy, but not after truncal vagotomy and truncal vagotomy plus ganglionectomy, intravenous atropine (14 nmol.kg-1.h-1) significantly reduced the incremental bicarbonate response to low (1.5 and 3 mmol/h) but not high loads of HCl. Neither the different surgical procedures nor atropine significantly altered plasma levels of secretin basally and in response to intestinal HCl. We conclude that 1) cholinergic fibers within the vagus nerves but not the splanchnic nerves are important mediators of the pancreatic bicarbonate response to low loads of HCl and 2) release of secretin by intestinal HCl is not under cholinergic and splanchnic control. PMID- 3348410 TI - Modulation of cell nucleotide levels of isolated kidney tubules. AB - The mechanisms responsible for the large increases of intracellular ATP levels seen after isolated rabbit proximal tubules are treated with exogenous adenine nucleotides were studied. Exogenous ATP was rapidly degraded via adenosine as far as hypoxanthine. Degradation of AMP to adenosine was substantially inhibited by beta-glycerol phosphate. In studies of the ability of individual exogenous purines to increase intracellular ATP levels, single large doses of adenosine were less effective than equimolar doses of exogenous ATP but were substantially more effective than exogenous inosine or hypoxanthine. Exogenous guanine derived compounds increased only cell GTP. Incremental delivery of smaller doses of adenosine to maintain medium levels greater than 5 microM or inhibition of adenosine deaminase with erythro-9-[3-(2-hydroxynonyl)]adenine or 2' deoxycoformicin enhanced the nucleoside's effectiveness. However, the initial increase of cell ATP was still greater after treatment with exogenous ATP than after adenosine and, in the presence of adenosine deaminase inhibition, larger increases of cell ATP were produced by 50 microM adenosine than by 250 microM adenosine. These observations are most consistent with substrate inhibition of adenosine kinase by adenosine. Furthermore, the adenosine kinase inhibitor, 5 iodotubercidin, prevented the increases of cell ATP resulting from exogenous adenosine or exogenous ATP. These studies demonstrate how the differential uptake and utilization characteristics of nucleosides and bases can fully account for the increases of intracellular nucleotides produced in isolated tubules by exogenous purines. PMID- 3348411 TI - Transition of permeability properties along the descending limb of long-loop nephron. AB - The isolated segments of the hamster descending limb of the long-loop nephron (LDL) were perfused in vitro to demonstrate the axial heterogeneity with respect to permeability properties. When a NaCl gradient from the lumen to bath was present, the lumen-negative diffusion voltage (VD) was generated in the upper portion (LDLU). When the VD was measured stepwise along the axis of tubules, the magnitude of the VD decreased in the portion within 0.5 mm before the border between the outer and inner medulla in most cases, indicating that a gradual functional transition to the lower portion (LDLL) occurs along the descending limb. The lumen-to-bath flux coefficients (K1----b) for Na+ were 14.3 +/- 3.7 X 10(-7) and 2.4 +/- 0.8 X 10(-7) cm2/s in the LDLU and LDLL, respectively. The K1- --b for urea were 1.7 +/- 0.6 X 10(-7) and 7.9 +/- 4.1 X 10(-7) cm2/s, respectively. The LDLL was highly permeable to water, with osmotic permeability coefficient being 1,693 +/- 517 X 10(-9) cm2.s-1.atm-1. The reflection coefficients for NaCl and urea were not different from unity. From these observations, we conclude that the functional transition occurs along the LDL from the segment with a high Na+ permeability to that with a low Na+ permeability. PMID- 3348412 TI - Kinetic model for phosphate transport in renal brush-border membranes. AB - Phosphate transport was studied in brush-border membrane vesicles purified from rat kidney cortex. Influx and efflux were strongly dependent on the presence of cis sodium; the rate of efflux, calculated by linear regression performed on the first time points, was much lower than the rate of influx (0.044 vs. 0.198 pmol.microgram protein-1.s-1). Trans phosphate had a stimulatory effect on phosphate influx (145% stimulation at 10 mM phosphate trans, with 0.2 mM phosphate cis). Trans phosphate was, however, inhibitory for phosphate efflux (89% inhibition at 10 mM phosphate trans). Trans effects of sodium were also studied. With 200 mM trans sodium, we observed 73% inhibition of phosphate influx and 60% inhibition of phosphate efflux. Studies involving sodium and phosphate present at the same time as trans substrates showed that the trans inhibition of phosphate influx by sodium could be completely reversed by trans phosphate. Trans inhibition of phosphate efflux by phosphate was not additive to the inhibition caused by sodium. Addition of trans phosphate had a stimulatory effect on sodium independent influx, indicating that the binary complex (C-P) could translocate in efflux. These results indicate that the renal phosphate carrier presents a random binding scheme for the intra- and extravesicular sides of the membrane. PMID- 3348413 TI - Intrarenal renin-angiotensin system modulates glomerular angiotensin receptors in the rat. AB - The aim of this study was to test the hypothesis that the intrarenal renin angiotensin system (RAS) modulates glomerular angiotensin II (ANG II) receptors. In one protocol ANG II receptors were measured 7 days after unilateral denervation of the left kidney in rats. There were 50% more receptors in the glomeruli from denervated compared with innervated kidneys (right, 1,037 +/- 108 vs. left, 1,556 +/- 143 fmol/mg; P less than 0.01), which was associated with a 63% reduction (P less than 0.01) in left renal vein renin. The differences in ANG II receptors between the left and right kidneys were no longer present when angiotensin-converting enzyme was inhibited with enalapril or when pharmacological amounts of ANG II (50 ng/min) were infused. In a second protocol, renal cortical renin content was raised in the left kidney by placing a 0.20-mm clip on the left renal artery (two-kidney, one-clip Goldblatt model). At 7 days, glomerular ANG II receptors were reduced by 72.3% in the clipped compared with the contralateral kidneys (right, 1,232 +/- 105 vs. left, 341 +/- 170 fmol/mg; P less than 0.01). The differences in ANG II receptors were no longer present after enalapril treatment. Pharmacological maneuvers that either blocked ANG II formation or increased circulating ANG II resulted in an equal number of ANG II receptors in the right and left kidneys. The data indicate that the intrarenal RAS modulates the density of glomerular ANG II receptors and is a more important receptor modulator than plasma ANG II. PMID- 3348414 TI - Electrophysiology of renal capillary membranes: gel concept applied and Starling model challenged. AB - In the classical Starling model the hydrostatic pressure in the pores is generally lower than that in capillary plasma, a phenomenon that necessitates the assumption of a rigid porous membrane. In flexible gel membranes, the capillary pressure is suggested to be balanced by a gel swelling pressure generated by negative fixed charges. Regarding the fluid transfer, the transmembranous electrical potential gradient will generate a net driving electroosmotic force. This force will be numerically similar to the net driving Starling force in small pores, but distinctly different in large pores. From previous data on the hydrostatic and colloid osmotic forces, the fixed charge density at the two interfaces of 1) the glomerular and 2) the peritubular capillary membrane were calculated and used to predict the flux of a series of charged protein probes. The close fit to the experimental data in both the capillary beds is in line with the gel concept presented. The gel concept (but hardly a rigid membrane) explains the ability of capillary membranes to alter their permeability in response to external forces. Gel membranes can furthermore be predicted to have a self rinsing ability, as entrapped proteins will increase the local fixed charge density, leading to fluid entry into the region between the particle and the pore rim, which by consequent widening of the channel will facilitate extrusion of trapped proteins. PMID- 3348415 TI - Parathyroid hormone impairs extrarenal potassium tolerance in the rat. AB - The effect of parathyroid hormone (PTH) on the extrarenal disposition of an acute potassium load was examined in acutely nephrectomized rats infused with KCl (0.75 meq.kg-1.h-1 for 90 min) alone or in combination with 8-10 U.kg-1.min-1 PTH, with serial monitoring of plasma potassium every 10 min. The rise in plasma potassium concentration (delta PK) in the PTH group was higher than control. PTH was then administered along with KCl to two groups of nephrectomized and acutely thyroparathyroidectomized (TPTX) rats in doses of 1 and 0.25 U.kg-1.min-1 for 90 min. delta PK with PTH in both groups was higher than TPTX control (P less than 0.01). The two higher doses of PTH resulted in a decrease in mean arterial pressure from their respective controls. A similar reduction in arterial pressure in three groups of nephrectomized rats by administration of hydralazine or nitroprusside or by acute blood loss did not change delta PK subsequent to potassium infusion from that in control rats. Furthermore, the lowest dose of PTH did not lower arterial pressure from its respective control. Therefore, hypotension is not a cause for the PTH-induced potassium intolerance. Serum levels of insulin, aldosterone, catecholamines, calcium, plasma HCO3 concentration, and pH were not different in PTH-infused vs. respective control rats. These data suggest that PTH impairs extrarenal potassium disposal in the rat. The effect of PTH may relate to enhanced calcium entry into cells. PMID- 3348416 TI - Mechanisms of H+ secretion by inner medullary collecting duct cells. AB - Inner medullary collecting duct cells were isolated from rat papillae and grown to confluence on cover slips. H+ secretion was estimated by intracellular pH (pHi) changes measured with the fluorescent probe 2,7-biscarboxyethyl-5(6) carboxyfluorescein. In buffered NaCl, pHi was 7.14 +/- 0.04 (n = 78). After acidification about 40% of monolayers exhibited Na+-independent alkalinization. In 5 mM glucose, cell alkalinization occurred at a rate of 47 +/- 4 nM H+/min. However, cell alkalinization did not occur in the presence of 2-deoxy-D-glucose (5-15 mM), iodoacetate (5 mM), or KCN (5 mM). All monolayers tested exhibited amiloride-inhibitable Na+-dependent cell alkalinization that appeared to be a first-order kinetic process; Km [Na+] was approximately 52 mM and Vmax was approximately 250 nM [H+]/min. At a constant extracellular [Na+] (110 mM), Na+ dependent H+ efflux was a first-order function of pHi; Km for intracellular [H+] = 321 nM and Vmax = 182 nM H+/min. The data are consistent with the presence of a primary active H+ pump and a secondary active Na+ exchanger. The metabolic energy for the active H+ pump can be provided by glycolysis and oxidative phosphorylation. PMID- 3348417 TI - Potassium adaptation: 39K-NMR evidence for intracellular compartmentalization of K+. AB - To investigate the effects of K+ uptake on the intracellular environment, both 39K-nuclear magnetic resonance (NMR) and K+-selective electrodes were used to measure K+ activity with acute K+ loading in control and K+-adapted rats. These results were then compared with tissue K+, measured by flame photometry. There was a lower NMR K+ visibility (ratio of NMR signal to tissue content) in muscle and liver in K+-adapted rats, compared with controls before and after an acute K+ load. This lower K+ visibility in K+-adapted rats was confirmed in liver homogenate with the K+-specific electrode. In liver homogenates from control and K+-adapted rats, addition of RbCl (300 mumol/g) increased the NMR K+ signal more in K+-adapted rats (19 +/- 1.1 mumol/g) than controls (11 +/- 1.0 mumol/g, P less than 0.01). This is consistent with the displacement of K+, by Rb+, from NMR undetected sites. These results suggest that some 10-15% of intracellular K+ may be within a compartment not detectable by NMR or electrodes and that chronic K+ loading leads to an increased capacity of this compartment. PMID- 3348418 TI - Metabolic substrate utilization by rabbit proximal tubule. An NADH fluorescence study. AB - The effects of various short-chain fatty acids, carboxylic acids, and amino acids on NADH fluorescence and oxygen consumption (QO2) of rabbit proximal tubule suspensions were determined. The short-chain fatty acids were the most effective substrates in increasing NADH fluorescence and QO2, followed by the carboxylic acids and amino acids. All of the substrates tested that increased NADH fluorescence proportionally increased QO2. This implies that the primary effect of these substrates was to increase QO2 by increasing the delivery of reducing equivalents to NAD and not by stimulating ATP hydrolysis directly. The relative affinity of several substrates to increase NADH fluorescence was also determined. The short-chain fatty acids had the highest affinity (10 microM range) followed by the carboxylic acids (100 microM range). These data demonstrate that the metabolic rate and NADH redox state of the renal cortical cell is very sensitive to the type of metabolic substrate available. PMID- 3348419 TI - Glomerular hemodynamic adaptations in remnant nephrons: effects of verapamil. AB - Chronic verapamil administration has been shown to reduce the renal dysfunction, glomerular sclerosis, and mortality in partially nephrectomized rats; the mechanism is unknown. Therefore, the present micropuncture study examines the effect of verapamil on glomerular hemodynamics of Munich-Wistar rats 4 wk after five-sixths nephrectomy. Whole-kidney function was similar in nephrectomized rats treated with verapamil (Nx-VER) and saline (Nx-SAL), and glomerular filtration rate (GFR) was one-third of control. Both Nx-VER and Nx-SAL rats exhibited a similar degree of glomerular hyperperfusion and hyperfiltration. However, mean glomerular capillary hydrostatic pressure difference (delta P) was lower in Nx VER than Nx-SAL rats (42.4 +/- 1.2 vs. 47.2 +/- 1.0 mmHg, P less than 0.005) because of an increase in Bowman's space hydrostatic pressure (PBS) in Nx-VER rats (15.5 +/- 0.8 vs. Nx-SAL 11.9 +/- 0.7 mmHg, P less than 0.005). Glomerular ultrafiltration coefficient (LpA) was significantly lower in Nx-SAL (P less than 0.005) than in Nx-VER or control rats. Urinary protein excretion and the magnitude of glomerular sclerosis in Nx-SAL and Nx-VER rats were not different. In conclusion, chronic VER administration normalizes LpA and reduces delta P, by increasing PBS, in Nx rats, alterations that neutralize each other, leading to the constancy of single-nephron GFR. PMID- 3348420 TI - Juxtaglomerular interstitial hypertonicity in Amphiuma: tubular origin-TGF signal. AB - One of the mechanisms mediating renal vascular autoregulation in mammals senses tubular flow rate-dependent changes in luminal NaCl concentrations and signals renal arterioles to change diameter. A similar mechanism operates in the salamander, Amphiuma means. To trace the signal, we measured chloride activity in juxtaglomerular interstitial spaces in Amphiuma during perfusion of the early distal tubule belonging to the same nephron. Interstitial Cl- activity exceeded systemic levels and increased when perfusion rate in the adjacent early distal tubule was increased, reaching values more than five times isotonic. Bumetanide, which inhibits NaCl transport by the early distal tubule, eliminated the hypertonicity. Regions of the interstitial space not a part of the juxtaglomerular apparatus (JGA) were not hypertonic. The Cl- concentration was 80% greater than isotonic in the JGA of nephrons studied under free-flow conditions. Single-nephron blood flow, measured by counting the flux of erythrocytes labeled with a fluorescent molecule, showed typical feedback inhibition with maximum sensitivity to the same rates of tubular perfusion that caused the maximum change in JGA interstitial hypertonicity. Juxtaglomerular interstitial hypertonicity could be an important part of the signal for renal autoregulation. PMID- 3348421 TI - Effects of hemodilution on skin microcirculation. AB - Red blood cell (RBC) velocity, capillary hematocrit (Hctcap), RBC flux, and arteriolar diameter were studied in the subcutaneous connective tissue of the Syrian hamster skinfold window preparation during successive normovolemic hemodilutions with 6% solutions of Dextran 70. The experiments were carried out in the unanesthetized animal. Heart rate (HR), mean systemic arterial pressure (Psys), and systemic hematocrit (Hctsys) were monitored throughout the procedure to ensure that normovolemia was maintained and hemodilution caused no adverse effects. The changes of RBC flux in the hemodiluted state, up to 50% hemodilution (Hctsys = 25% +/- 4), were not statistically significant when compared with control (t test, P less than 0.5). At this Hctsys, capillary RBC velocity increased by 60% and Hctcap decreased by 30%. Both of these changes were statistically significant relative to control. The arteriolar diameter did not change significantly during the reduction of Hctsys. The animals were studied during subsequent days to determine the chronic effects of hemodilution. Hctsys increased by approximately 12% per day after the experiment, and the systemic parameters returned to the prehemodiluted state in direct proportion to the reestablishment of the Hctsys. PMID- 3348422 TI - Adenosine deaminase attenuates norepinephrine-induced coronary functional hyperemia. AB - Responses to norepinephrine (NE) before and after treatment with adenosine deaminase (ADA) were examined in anesthetized dogs. In four dogs repeatable changes in coronary blood flow, myocardial oxygen extraction and consumption, left ventricular +dP/dtmax, and heart rate (HR) were demonstrated during two successive intracoronary infusions of 0.13 micrograms.kg-1.min-1 NE. In eight dogs, the NE-induced hyperemia was decreased from +150 to +67%, the change in myocardial oxygen consumption (MVo2) was attenuated from +177 to +101% by ADA, and the increase in HR was reduced from +28 to +16%. In six dogs, the increase in HR caused by NE before ADA was maintained after ADA by atrial pacing. The NE induced hyperemia and the increase in MVo2 were again decreased by ADA. Similar results were observed in 12 other dogs with hearts paced at a constant, elevated rate during control as well as during both infusions of NE. In all groups, the O2 extraction response to increased MVo2 increased and the flow response decreased after ADA. In six dogs nitroprusside was infused during NE after ADA. When coronary flow was restored to the same level observed before deaminase, MVo2 was not diminished. These results support a role for adenosine in the coronary functional hyperemia accompanying NE activation of the canine myocardium. PMID- 3348424 TI - Distensibility of hepatic venous resistance sites and consequences on portal pressure. AB - Hepatic venous resistance was measured in cats anesthetized with pentobarbital sodium during changes in hepatic blood flow and in inferior vena cava (IVC) pressure, in an attempt to explain the variable and partial transmission of pressure from IVC to portal vein. Problems with earlier explanations based on a "vascular waterfall" or a "Starling resistor" are discussed. Our data and previously published data can be explained by the hypothesis that hepatic venous resistance decreases as the resistance site is distended by the pressure within the resistance vessels. The product of resistance and distending pressure was a constant. This constant equals the resistance at unit-distending pressure, and it is an index of active contraction of the resistance sites in acute experiments. It is increased during infusions of norepinephrine, and it is higher in innervated than in denervated livers. A distensible hepatic venous resistance is a passive mechanism for partial autoregulation of portal pressure. It also serves as a mechanism for regulation of the splanchnic capacitance response to changes in IVC pressure. PMID- 3348423 TI - Cardiovascular effects of AVP and ANG in experimental pulmonic stenosis in rats. AB - Our objectives were to examine the role of vasopressin and renin in the regulation of peripheral vascular tone in an animal model of right ventricular failure due to chronic (10 wk) pulmonic stenosis. We tested in chronically instrumented conscious control rats and in rats with pulmonic stenosis on a normal and a high-sodium diet both vasoconstrictor systems by applying specific inhibitors. The rats with pulmonic stenosis showed significant hemodynamic changes, a hypertrophy of the right ventricle, increased levels of plasma renin concentration, and inappropriately elevated plasma levels of vasopressin in comparison to control animals. Plasma renin concentration was suppressed in the sodium-loaded controls. After the administration of a specific inhibitor of the vascular receptors of arginine vasopressin [30 micrograms, d(CH2)5Tyr(Me)AVP], we found no hemodynamic changes in control rats on the normal diet, a reduction of mean arterial pressure in the sodium-loaded controls (4 +/- 4 mmHg; P less than 0.005), and in the animals with pulmonic stenosis and normal sodium intake (5 +/- 5 mmHg; P less than 0.001) and high-salt diet (6 +/- 7 mmHg; P less than 0.02). Intravenous bolus injection of teprotide (1 mg/kg) resulted in a decrease of mean arterial pressure in the control group (normal diet) of 9 +/- 8 mmHg (P less than 0.005). The fall of blood pressure (22 +/- 10 mmHg; P less than 0.001) in the rats with pulmonic stenosis was significantly greater (P less than 0.01) and was strongly related to plasma renin concentration. Therefore, vasopressin and the renin-angiotensin system contribute to an increase of peripheral vascular tone in chronic pulmonic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348425 TI - Influence of risk area size and location on native collateral resistance and ischemic zone perfusion. AB - To examine the effect of risk area size on collateral resistance and ischemic region perfusion, we produced different sized risk areas by occluding either the left anterior descending (LAD) or the circumflex (Cx) coronary artery at different sites. The most proximal occlusion of the LAD and Cx produced risk areas of 43 +/- 5 and 36 +/- 2% of left ventricular (LV) mass, respectively, whereas distal LAD and Cx occlusions produced risk areas of 13 +/- 2 and 17 +/- 2% of LV weight, respectively. Although total collateral flow was highest to the largest risk areas, collateral flow per 100 g of ischemic myocardium was 80% higher to the small LAD risk area compared with the large LAD risk area and 43% higher to the small Cx risk area compared with the large Cx risk area. Collateral resistance, calculated from the transcollateral pressure and perfusion per 100 g of myocardium was significantly lower in the small risk areas than in the large ones. We examined the effect of risk area location on collateral perfusion and resistance. Small risk areas (6% LV mass) were created near the base and at the apex of 10 hearts. Collateral flow per 100 g was 60% higher and transcollateral resistance per 100 g 50% lower at the apex than at the base. These experiments show that collateral resistance is influenced both by ischemic region size and location. Small risk areas receive more collateral flow per mass of tissue than large risk areas, and apical risk areas receive greater quantities of collateral flow than those located at the base.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348426 TI - fMLP provokes coronary vasoconstriction and myocardial ischemia in rabbits. AB - Recent pathological studies of coronary arteries from humans with suspected coronary spasm have revealed an augmented intramural burden of inflammatory cells. To test the hypothesis that inappropriate activation of inflammatory cells participates in the evolution of coronary vasospasm, the present experiments employed a newly developed coronary arteriographic technique for use in pentobarbital-anesthetized rabbits to evaluate the coronary vasomotor actions of the nonselective inflammatory cell stimulant, N-formyl-L-methionyl-L-leucyl-L phenylalanine (fMLP). In 10 of 10 animals, selective left intracoronary injection of 200 ng fMLP evoked profound left coronary narrowing accompanied in all cases by ST segment deviation and dysrhythmias. Thallium-201 scintigraphy demonstrated hypoperfusion of the left ventricular free wall and septum supplied by the spastic coronary artery. The fMLP-induced epicardial vaso-constriction, ischemic electrocardiogram (ECG) changes, and thallium perfusion defects were reversed by intravenous nitroglycerin. Neither the right coronary artery nor its distribution were influenced by left coronary injection of fMLP. Additional experiments in isolated, salt solution-perfused rabbit hearts demonstrated that fMLP failed to exert direct coronary vasoconstrictor effects. These observations indicate that the non-selective inflammatory cell stimulant, fMLP, provokes arteriographically demonstrable coronary spasm with attendant myocardial hypoperfusion and ischemic ECG changes in anesthetized rabbits. Such a model may be useful in exploring the dynamic role of inflammatory cells in development of coronary spasm. PMID- 3348427 TI - Effect of hypoxia on lung lymph flow in newborn lambs with left atrial hypertension. AB - To determine the effect of left atrial hypertension on the vascular response to hypoxia in the newborn lung, we measured pulmonary artery and left atrial pressures, lung blood flow and lymph flow, and concentrations of protein in lymph and plasma of 13 lambs that spontaneously breathed air for 2-6 h (control period), followed by 8-11% O2 mixed with 3-5% CO2 and N2 for 2-4 h (experimental period). In eight studies, the lambs were made hypoxic first, after which we elevated their left atrial pressure by 10-12 Torr for 2-3 h. In 10 additional studies, we reversed the sequence by raising left atrial pressure first followed by addition of hypoxia. In lambs with normal left atrial pressure, alveolar hypoxia increased both pulmonary blood flow and lymph flow, with an associated reduction in lymph-to-plasma protein ratio (L/P). When left atrial pressure was increased in the presence of hypoxia, lymph flow increased by a small amount and L/P decreased further. In lambs with preexisting left atrial pressure elevation, addition of alveolar hypoxia increased both blood flow and lymph flow with no significant change in L/P. These results suggest that in newborn lambs with normal left atrial pressure, alveolar hypoxia increases lung lymph flow mainly by increasing microvascular filtration pressure, whereas in lambs with elevated left atrial pressure, hypoxia increases lymph flow by another mechanism, perhaps by increasing the perfused surface area for fluid filtration. PMID- 3348428 TI - Effects of dietary fish oil on cardiac responsiveness to adrenoceptor stimulation. AB - The effect of dietary fish oil on cardiac function and responsiveness to alpha- and beta-adrenergic receptor agonists was examined in isolated perfused rat hearts. Rats were fed either a standard laboratory diet (SD) or diets containing 5% corn oil (CO) or 5% menhaden oil (MO) for 4 wk. When perfused as working preparations at varying preloads and afterloads, the peak aortic pressures, aortic outputs, and coronary flows were comparable in hearts of rats fed the three experimental diets. Inotropic responsiveness to phenylephrine was examined by infusing graded doses of the drug into the heart while monitoring changes in the rate of left ventricular pressure development (+dP/dt). Prior to phenylephrine administration +dP/dt was not different among the three groups of hearts. However, at each dose of phenylephrine employed, delta +dP/dt was approximately 50% less in hearts of rats fed MO when compared with either SD or CO. Thus cardiac inotropic responsiveness to this alpha-agonist was reduced by dietary fish oil. In contrast, cardiac inotropic responsiveness to isoproterenol was not altered with MO feeding. The data demonstrate that dietary fish oil results in alterations in alpha- but not beta-adrenoceptor mediated changes in cardiac inotropy. PMID- 3348429 TI - Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rat. AB - Angiotensin II, a vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of prostaglandins. Because of this effect, we investigated whether infusion of exogenous angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric hypoxia might prevent pulmonary hypertension, right ventricular hypertrophy, and vascular changes. We instrumented the rats with indwelling cardiovascular catheters and compared the hemo-dynamic and structural response in animals given angiotensin II, indomethacin in addition to angiotensin II (to block prostaglandin production), or saline with or without indomethacin. We then determined whether angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. We observed that exogenous angiotensin II infusion abolished the rise in pulmonary artery pressure, the right ventricular hypertrophy, and the vascular changes induced during chronic hypoxia in control saline-infused rats with or without indomethacin. The protective effect of angiotensin II was lost when indomethacin was given to block prostaglandin synthesis. During acute hypoxia, both angiotensin II and prostacyclin infusions similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given indomethacin or saralasin in addition to angiotensin II. Thus exogenous angiotensin II infusion prevents chronic hypoxic pulmonary hypertension, associated right ventricular hypertrophy, and vascular changes and blocks acute hypoxic pulmonary hypertension, and this is likely related to its ability to release vasodilator prostaglandins. PMID- 3348430 TI - Coronary hemodynamic responses during local hemodilution in canine hearts. AB - To evaluate the effect of hemodilution per se on coronary hemodynamics, experiments were performed in 36 anesthetized, open-chest dogs whose left anterior descending coronary artery (LAD) was perfused selectively with either normal arterial blood or arterial blood diluted with lactated Ringer solution. LAD blood flow (CBF) was measured with an electromagnetic flowmeter and its transmural distribution assessed with 15-microns radioactive microspheres. LAD perfusion pressure was set at the normal level (approximately 100 mmHg) or at 50% of that level to simulate coronary insufficiency. Dilator reserve capacity was calculated from ratio of reactive hyperemic peak flow following release of 90-s occlusion to control (preocclusion) flow. Systemic hemodynamic parameters were maintained near control values during coronary hemodilution. With perfusion pressure normal, graded hemodilution caused progressive, transmurally uniform increases in CBF that showed a nonlinear relationship to inflow hematocrit. Increased peak reactive hyperemic flow and decreased dilator reserve ratio indicated that both reduced viscosity and vasodilation contributed to increased CBF during hemodilution. Hypotension alone reduced CBF, with greater effect in the subendocardium. Additional hemodilution returned CBF to normotensive value, but relative subendocardial hypoperfusion persisted. The present study provides fundamental information on effects of hemodilution on coronary hemodynamics without the systemic responses that complicated previous studies utilizing whole body exchange transfusions. PMID- 3348431 TI - Ventricular preload alters intravascular and extravascular resistances of coronary collaterals. AB - Coronary collateral blood flow is determined by both the collateral vessel resistance and a waterfall mechanism. The aim of this study was to determine which of these two mechanisms predominates during alteration of ventricular preload. The left anterior descending coronary artery of 12 anesthetized dogs was cannulated, and the distal vasculature was completely embolized with 25-micron diameter microspheres. Retrograde blood flow (RBF) was collected when the cannula was opened to the atmosphere, and the outflow tubing height was adjusted to provide a variable back pressure. RBF is back pressure-dependent at higher back pressures, and the slope in this region of the constructed pressure-flow relationship determines the collateral conductance. The transition point between the back pressure-dependent and a back pressure-independent region indicates a waterfall pressure impinging on the collateral vessels. At a left ventricular diastolic pressure of 9.3 mmHg, mean RBF, collateral conductance, and the collateral waterfall pressure were 7.3 ml/min, 0.175 ml.min-1.mmHg-1, and 30.1 mmHg, respectively. Corresponding values when preload was reduced to 3.5 mmHg were 9.3 ml/min, 0.186 ml.min-1.mmHg-1, and 23.7 mmHg, all changes being significant. Mean contribution to the overall increase in RBF was 0.5 ml/min for the conductance and 1.2 ml/min for the waterfall mechanism (P less than 0.05), or 29 and 71%, respectively. The results indicate that the extravascular resistance mechanism mediates the collateral flow response to a greater degree than the intravascular resistance during variations in preload. The increase in slope of the conductance portion of the relationship was not accompanied by a concomitant increase in slope of the back pressure-independent region. These data further support a collateral waterfall, and not collateral vessel compliance, as the basis for the back pressure-independent portion of the pressure-flow relationship. PMID- 3348432 TI - Development of pulmonary vascular response to oxygen. AB - The ability of the pulmonary circulation of the fetal lamb to respond to a rise in oxygen tension was studied from 94 to 146 days of gestation. The unanesthetized ewe breathed room air at normal atmospheric pressure, followed by 100% oxygen at three atmospheres absolute pressure in a hyperbaric chamber. In eleven near-term lambs (132 to 146 days of gestation), fetal arterial oxygen tension (PaO2) increased from 25 +/- 1 to 55 +/- 6 Torr (mean +/- SE), which increased the proportion of right ventricular output distributed to the fetal lungs from 8 +/- 1 to 59 +/- 5%. In five very immature lambs (94 to 101 days of gestation), fetal PaO2 increased from 27 +/- 1 to 174 +/- 70 Torr, but the proportion of right ventricular output distributed to the lung did not change, 8 +/- 1 to 9 +/- 1%. In five of the near-term lambs, pulmonary blood flow was measured. It increased from 34 +/- 3 to 298 +/- 35 ml.kg fetal wt-1.min-1, an 8.8 fold increase. We conclude that the pulmonary circulation of the fetal lamb does not respond to an increase in oxygen tension before 101 days of gestation; however, near term an increase in oxygen tension alone can induce the entire increase in pulmonary blood flow that normally occurs after the onset of breathing at birth. PMID- 3348433 TI - Influence of site of regional ischemia on LV cavity shape change in dogs. AB - We assessed whether altering the location of acute ischemia produced differing and consistent changes in cavity shape in the canine left ventricle. Twenty anesthetized open-chest dogs underwent transient occlusion of the left anterior descending (LAD) or circumflex (Circ) artery, and cavity shape change was recorded in two-dimensional short-axis echocardiograms. The extent of injury was assessed by radiolabeled microspheres. Shape was analyzed by converting digitized endocardial contours into polar form and expressing the result as a Fourier series. Series terms reflected specific shape deformations, i.e., 2nd term would equal "elongation," 3rd term would equal "triangular." During LAD occlusions, 32.5 +/- 3.0% of the ventricle was hypoperfused compared with 29.8 +/- 2.9% during Circ occlusions (NS). Normal ventricular shape became more circular during ejection indicated by a reduction in the power in nearly all of the Fourier spectra components. During Circ occlusion, the chamber became more elongated, seen in a 63 +/- 16% rise in the 2nd component, and overall shape significantly less circular at end systole than at end diastole. LAD occlusion produced an entirely different pattern, one with no significant elongation but the development of a more triangular shape (86 +/- 27% rise in the 3rd term) by end systole. We conclude that there are characteristic and contrasting shape deformations in LV short-axis contours that depend on the site of ischemic injury. These changes may relate to site-specific geometry and loading, and they point to potential limitations of left ventricular models that do not account for regional inhomogeneity. PMID- 3348434 TI - Measurement of hydroxy-conjugated dienes after ischemia-reperfusion in canine skeletal muscle. AB - Recent studies have suggested that oxygen-derived free radicals are involved in the reperfusion injury of ischemic skeletal muscle. Although postischemic necrosis and increased vascular permeability have been attenuated with the addition of free radical scavengers, no unequivocal chemical evidence for free radical injury in skeletal muscle is available. The purpose of this study was to identify products of free radical-mediated membrane injury by isolation of lipid oxidation products (hydroxy-conjugated dienes) from postischemic skeletal muscle. The bilateral canine gracilis muscle model was used, and in each pair one muscle was exposed to 3 and the other to 5 h of normothermic ischemia. Muscle biopsies were taken before and at end ischemia, as well as during the first 3 h of reperfusion. Phospholipids were extracted from the muscle biopsies and the fatty acids hydrolyzed from the 2 position. After methylation, the oxidized fatty acid esters were separated by high-performance liquid chromatography. Hydroxy diene peaks absorbing at 235 nm were collected and subjected to gas chromatography-mass spectrometry (GC-MS) for positive structural identification. No significant increase in the level of conjugated dienes occurred during ischemia. Significant increases, however, were detected during the period of reperfusion, although the time when peak levels were achieved varied between animals. The cumulative sum of dienes produced during reperfusion in both 3- and 5-h muscles was significantly increased over pre- and end-ischemic values. The hydroxy-conjugated diene isomers of 18:2 and 20:4 were positively identified in reperfusion biopsies by GC-MS. These studies provide chemical evidence of free radical-mediated lipid oxidation during reperfusion of ischemic skeletal muscle. PMID- 3348435 TI - Relationship between endocardial activation of SA valve and right atrium in domestic fowl. AB - We mapped endocardial activation in the isolated, perfused chicken heart to determine how excitation spreads from the sinoatrial (SA) valve, the avian pacemaker structure, to the atrioventricular (AV) ring. We found activity originating from one of three sites on the right valvule with the upper half of this valvule being the dominant origin. Only one heart exhibited an origin lower on the right valvule. We never observed activity originating from the left valvule. Depending on the valvular origin, two patterns of atrial activation were observed. The dominant pattern emerged from an upper to middle origin on the right valvule and involved two preferential conduction pathways. One pathway followed the right transverse arch and pectinate muscle medially to depolarize the AV ring from a posterior medial direction. Activation along the second pathway traveled caudally along the right valvule and then followed the sinus septum to approach the AV ring from an anterior lateral direction. An atypical pattern resulted from one heart exhibiting a lower origin on the right valvule. In this case, preferential atrial conduction only followed the lower pathway. This could represent an entrance block located cranially in the right valvule preventing normal activation of the right transverse arch and pectinate muscle. PMID- 3348436 TI - Cardiac energetics and performance of exercised and food-restricted rats during aging. AB - The effects of exercise and food restriction on hemodynamic and metabolic characteristics of the heart during aging were studied in male, retired breeder, Fischer 344 rats. At the age of 10 mo they were divided into three groups: 1) sedentary and ad libitum fed (S); 2) sedentary and food restricted by alternate day feeding (R); and 3) exercised 20 min/day on a treadmill and ad libitum fed (E). Isolated, perfused working hearts were analyzed at 10 (S only), 18, 24, and 30 mo. Groups E and R demonstrated significant improvements (P less than 0.01) at 18 mo for cardiac output (ml.min-1.g-1), pressure work (kg.m.min-1.g-1), and efficiency (%). These performance parameters declined (P less than 0.01) after 18 mo in all groups; however, at 24 mo, E maintained higher values (P less than 0.01) for these parameters than S or R. At 30 mo, all groups were similar. Levels of high-energy phosphate compounds or lactate release were not affected by age or treatment. An age-related increase (P less than 0.05) in left ventricular hexokinase activity was observed in all groups. Activities of rate-determining enzymes of Krebs cycle or content of cytochromes were not affected by age. We conclude from this metabolic profile that energy production is not impaired in the aged Fischer 344 rat heart. PMID- 3348437 TI - A model of the systemic arterial bed showing ventricular-systemic arterial coupling. AB - A multielement model of the systemic arterial bed was implemented on a microcomputer and was used to simulate the transient response of the arterial circulation to a specific driving function: a linearly increasing left ventricular pressure. The elements (compliances and inductances) that simulate the aorta and its branches are determined by the characteristic impedances and time delays in the arterial system. The simulations of pressure and blood velocity signals found in a previous version of the model were improved by making the delays in the system nonuniform, with slow central and rapid peripheral wave speeds. This reduced the impedance into which the heart has to pump and increased the distal impedance, raising the peripheral diastolic pressures. When the reflection coefficient was decreased as the heart rate was increased, normal pressure and velocity signals could be maintained over a range of heart rates up to 150 min-1. Extrapolating this relationship to a heart rate of 200 min-1 indicated that the reflection coefficient could be zero at that heart rate, giving optimal power transmission through the arterial bed. PMID- 3348438 TI - Hormonal and renal responses to water drinking in moderately trained and untrained humans. AB - Endurance exercise training alters the regulation of body fluids. To investigate specifics of these alterations, hormonal, electrolyte, and renal responses to water ingestion (1% of lean body wt) were studied in six moderately trained (T) and 6 untrained (UT) male subjects. No differences between groups for base-line hormonal, electrolyte, or renal measurements were found. After water ingestion, atrial natriuretic factor remained unaltered in both groups. Predrink plasma antidiuretic hormone (ADH) levels of 0.51 +/- (SE) 0.19 (UT) and 0.47 +/- 0.07 microU/ml (T) remained unchanged in the T group but were reduced from min 9 through 90 in the UT group. At 30 min postdrink, UT subjects had lower ADH values than T subjects (0.18 +/- 0.02 vs. 0.33 +/- 0.05 microU/ml), while plasma osmolality was similarly reduced by approximately 3 mosmol/kg in both groups. Urine flow rates increased in both groups from similar values of 0.85 +/- 0.24 (UT) and 0.67 +/- 0.11 ml/min (T) to peak flows of 4.6 +/- 1.6 for UT and 2.7 +/- 1.1 ml/min (T) to peak T, P less than or equal to 0.05) at 60 min postdrink. Urine osmolality was reduced from similar values of 809.1 +/- 62.1 and 867.0 +/- 56.1 mosmol/kg to values of 248.8 +/- 87.6 and 469 +/- 146.1 mosmol/kg for UT and T, respectively (UT vs. T, P less than 0.05), at 60 min. Reduced ADH before reductions in plasma osmolality in the UT but not the T subjects suggests that T subjects have a reduced oropharyngeal inhibition of ADH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348439 TI - A slow potassium conductance after action potential bursts in rabbit vagal C fibers. AB - Sucrose gap recordings were made from vagus nerve in rabbit to examine the mechanisms underlying the generation of the hyperpolarization that follows a burst of evoked action potentials in unmyelinated C fibers. Analysis of the posttetanic hyperpolarization was made by fitting the membrane potential changes with the sum of two exponential components. The posttetanic hyperpolarization consisted of two separable components with time constants of approximately 0.5 and 30 s. The slower exponentially decaying component was dependent on an increase in electrogenic sodium pumping as shown by the effect of ouabain and changes in extracellular chloride. The faster-decaying exponential component was caused by a potassium conductance as shown by the effect of varied extracellular potassium. This potassium conductance appears to be novel as its dynamics vary with the frequency and duration of the burst yet increases in reduced calcium. It is suggested that this slow decaying and modifiable potassium conductance can play a role in modulation of preganglionic and presynaptic action potential conduction. PMID- 3348440 TI - Cold- and norepinephrine-induced thermogenesis in younger and older Fischer 344 rats. AB - Older rats exposed to low environmental temperatures show attenuated thermogenesis. However, the mechanisms responsible for this attenuation are not clear. This investigation evaluated the possibility that reduced nonshivering thermogenic capacity is associated with this attenuation. O2 consumption was measured in male Fischer 344 rats ages 7 and 24 mo at thermoneutrality (26 degrees C), during exposure to cold (6 degrees C) for 2 h, and during norepinephrine (NE) infusion (an in vivo measure of nonshivering thermogenesis). In addition, the binding of GDP to isolated mitochondria of brown fat, an in vitro estimate of nonshivering thermogenesis, was also measured. Resting mass independent O2 consumption (ml.min-1.g body mass -0.67) was not different between the two age groups. However, mass-independent O2 consumption was significantly greater in the younger vs. older rats during 2 h of cold exposure (younger, 2.86 +/- 0.19 l/kg body mass 0.67; older, 2.39 +/- 0.10 l/kg body mass 0.67) and during 20 min of maximum NE infusion (younger, 410.4 +/- 15.1 ml/kg body mass)] was greater in younger than ml/kg body mass 0.67). Brown fat mass [absolute (g) as well as relative (g tissue/kg body mass)] was greater in younger than in older rats. Furthermore, younger rats had significantly greater binding of GDP to isolated mitochondria of brown fat than did the older rats. This effect was true whether the data were expressed as nanomoles bound per milligram mitochondrial protein (32% lower in older rats), bound nanomoles recovered (57% lower), or bound picogram per kilogram body mass 0.67 (59% lower).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348441 TI - Osmoregulation in pseudopregnant and prolactin-treated rats: comparison with normal gestation. AB - Osmoregulation was studied throughout rodent pregnancy focusing on the importance of the fetoplacental unit and prolactin in the observed alterations. Plasma osmolality (Posmol) and plasma sodium (PNa), similar in 8-day gravid and virgin Sprague-Dawley rats, decreased significantly by gestational day 10, reaching a nadir 8-10 mosmol/kg and 3-5 meq/l, respectively, below virgin levels by day 14 (both P less than 0.001). Despite this, plasma arginine vasopressin (PAVP) was measurable and similar in all pregnant and virgin groups. Osmotic thresholds for arginine vasopressin (AVP) secretion, similar in 8-day gravid and virgin rats, decreased 7.7 and 10.7 mosmol/kg in 12- and 14-day pregnant rats, respectively (both P less than 0.001). In contrast, Posmol decreased less than 2 mosmol/kg in 12- to 14-day pseudopregnant animals. When pseudopregnancy was prolonged to 18 days by prior hysterectomy, Posmol was only 2.6 mosmol/kg below that of cycling, hysterectomized controls. In other studies 14 days of hyperprolactinemia evoked by estradiol or treatment with ovine or rat prolactin had minimal effect on Posmol. We conclude that parallel decrements in Posmol and osmotic thresholds for AVP release occur during early rodent pregnancy, alterations that cannot be explained by gestational increases in circulating prolactin. In addition, the failure of pseudopregnancy. to mimic the hypotonicity of gestation suggests an important role for the fetoplacental unit in the osmoregulatory changes of rat pregnancy. PMID- 3348442 TI - Decreased hexokinase activity in paraventricular nucleus of adult SHR and renal hypertensive rats. AB - Metabolic activity was assessed in the brains of spontaneously hypertensive rats (SHR) using the histochemical hexokinase (HK) technique and photodensitometric analysis. Of eight regions known to play a role in cardiovascular regulation, only the paraventricular nucleus of the hypothalamus (PVH) exhibited alterations in HK activity. Significantly lower levels of HK activity in SHR than in control Sprague-Dawley and Wistar-Kyoto rats were measured in both the parvo- and magnocellular divisions of the PVH. No differences in HK activity were found in the anterior hypothalamic nucleus, posterior hypothalamic nucleus, supraoptic nucleus, subfornical organ, central nucleus of the amygdala, or the medial nucleus of the tractus solitarius of SHR. Similar results were obtained in renal hypertensive rats; furthermore, a positive correlation was found between levels of arterial pressure and densitometric readings. These latter results strongly suggest that metabolic alterations in the PVH of SHR are directly related to the increases in arterial pressure and are not due to the genetic makeup of SHR. In light of studies by others, the data from the present study have been interpreted to suggest that the decreases in metabolic activity in the PVH of the adult SHR are the result of a central attempt to bring the level of the arterial pressure down to normal levels and not to the altered activity of a region that might be acting to keep arterial pressure elevated. PMID- 3348443 TI - Subfornical organ and cardiovascular influences on identified septal neurons. AB - We have identified, in urethan-anesthetized male Sprague-Dawley rats, a polysynaptic pathway connecting the subfornical organ (SFO) with the paraventricular nucleus (PVN) with a relay neuron in the medial septum-diagonal band of Broca (MS-DBB). Extracellular recordings were obtained from 136 MS-DBB neurons antidromically identified as projecting to the PVN. SFO stimulation orthodromically activated 79% of these cells (mean latency, 21.2 +/- 0.6 ms; mean duration, 6.0 +/- 0.2 ms), whereas stimulation in the fornix or hippocampal commissure had no effect. Of 35 identified MS-DBB neurons tested with systemic angiotensin II (ANG II), eight showed increases and six decreases in excitability that coincided with the ANG II-induced increase in blood pressure. To determine whether such changes were blood pressure related, 23 of the 35 identified MS-DBB neurons tested with ANG II were tested with systemic epinephrine. In every case the effect of epinephrine was similar to that of ANG II. These findings suggest that neurons in the MS-DBB receive afferent information from the SFO and the cardiovascular system. These cells in turn may activate neurons involved in the control of a variety of autonomic functions. PMID- 3348444 TI - Role of adrenal medulla in hemodynamic response to hemorrhage and naloxone. AB - We tested the hypothesis that enkephalins or some other compound(s) released by the adrenal medulla during hemorrhage were responsible for the resultant hypotension. We compared the hemodynamic and plasma catecholamine responses to hemorrhage and subsequent opioid receptor blockade with naloxone in intact, adrenal-denervated (ADD), and adrenalectomized (ADX) rabbits. The studies were done in conscious, chronically prepared, male New Zealand White rabbits. The hemodynamic response to hemorrhage was not different among the three groups. Plasma norepinephrine (NE) increased early in hemorrhage in all groups. In the ADD and ADX animals, NE decreased significantly at the transition to hypotension, suggesting decreased release of NE by peripheral sympathetic nerves as a possible cause of the decrease in pressure. In the intact group, NE did not decrease but reached a plateau possibly due to the release of some NE by the adrenal medulla, which obscured the decreased release by sympathetic nerves. The pressor response to naloxone, though present in all groups, was attenuated by adrenalectomy or adrenal denervation. The plasma NE response to naloxone was similar in all groups and involved a two- to threefold increase after naloxone. We conclude that enkephalins or any other compounds released by the adrenal gland are not responsible for the acute hemodynamic changes during hemorrhage in the conscious rabbit. However, some substance(s) released by the adrenal medulla, perhaps epinephrine, does play a role in naloxone's pressor effect, since this is reduced by adrenalectomy or adrenal denervation. PMID- 3348445 TI - Empathy: misconceptions and misuses in psychotherapy. AB - The frequent misconceptions and misuses of empathy that occur during psychotherapy are related to confusion about the definition of empathy, misunderstanding of the difference between the process of empathy and the therapist's response of being empathic, countertransference exploitation of empathy to act out the therapist's needs, the therapist's unawareness of the "layering" phenomenon, and overlooking the patient's level of self-other differentiation. These misuses result in the patient's feeling misunderstood and damaged, with a subsequent weakening of the therapeutic alliance and, at times, a breakdown in self-other differentiation. Once identified, misuses should be addressed and explored in psychotherapy to offset disruptions in treatment. PMID- 3348446 TI - Personality pathology in recurrent depression: nature, prevalence, and relationship to treatment response. AB - Personality assessments of 119 treatment-responsive patients with recurrent unipolar depression revealed that nearly half of the patients (48%) showed some personality disturbance. The most common personality features were avoidant (30.4%), compulsive (18.6%), and dependent (15.7%). Factor analyses of personality data in this homogeneous population yielded results that were consistent with previous factor analytic studies of personality features and clinical descriptions of depressed patients. Most notably, a discriminant function analysis using personality variables alone was able to distinguish (with 65% accuracy) between patients who responded normally to treatment and those who responded more slowly. PMID- 3348447 TI - Court-mandated community outpatient treatment for persons found not guilty by reason of insanity: a five-year follow-up. AB - The authors conducted a 5-year follow-up study of 79 persons found not guilty by reason of insanity who were referred to and accepted for court-mandated community outpatient treatment. This was a severely mentally ill and violent group with extensive experience in both the criminal justice and mental health systems. This program was not without risks despite a readiness to revoke the patients' conditional release status when indicated; during the 5-year follow-up period, 25 (32%) were rearrested (18 [72%] for crimes of violence), 37 (47%) were hospitalized, and 38 (48%) had their conditional releases revoked. The authors believe that members of this population need social controls and long-term treatment when they are in the community. PMID- 3348448 TI - Types of patients served by various providers of outpatient care in CMHCs. AB - Representative community mental health center (CMHC) survey data showed that psychiatrists differed from other CMHC providers of mental health services by serving the more seriously impaired patients who are admitted and readmitted to outpatient services. Psychiatrists also shared more outpatients with providers from other disciplines than providers in other disciplines shared with one another. The results are consistent with previous research on differences between disciplines and with the flight of psychiatrists from CMHCs but cast doubt on the hypothesis that psychiatrists see sicker patients than psychologists see because of differences in reimbursement between the two disciplines. PMID- 3348449 TI - Diagnostic classification through content analysis of patients' speech. AB - Speech samples from 71 patients in four diagnostic groups were analyzed by two quantitative methods of speech content analysis, the results of which were entered into a discriminant analysis to test whether patients could be accurately classified back into their appropriate diagnostic groups. These classifications were compared with classifications made by two psychiatrists, blind to the patients' diagnoses, who read transcripts of the speech samples. The results suggest that data from the systematic quantification of lexical choice can be used to classify patients into their respective diagnostic groups and that this classification compares favorably with that done by psychiatric raters. PMID- 3348450 TI - The definition of a psychiatrist: eight years later. AB - In 1980, psychiatric practitioners and educators were surveyed to determine their concepts of the knowledge and skills that define a specialist in psychiatry. The authors repeated this survey, expanding the list of skill and knowledge items and asking respondents to comment on whether particular skills or knowledge were important to a psychiatric subspecialty. Less importance was ascribed in the current survey than in the earlier survey to certain long-term and social psychotherapies, and more importance was ascribed to descriptive or biological psychiatry; brief or supportive therapies; psychopharmacological agents; consultation-liaison psychiatry; evaluation of children, the aged, and alcoholics; and certain desirable personal characteristics of the psychiatrist. PMID- 3348451 TI - Training in geriatric psychiatry: will the supply meet the demand? AB - The number of geriatric patients with major psychiatric disorders is expected to grow along with the rising proportion of people age 65 and older. Despite recognition of this growth and increases in the training of geropsychiatrists, the supply of specialists is unlikely to keep up with the demand. The authors argue for greater resource expenditure in fellowship programs and a focus on training academic leaders to serve as role models for general psychiatrists and other primary care givers. PMID- 3348452 TI - Perceptions of parenting in childhood and social support in adulthood. AB - A group of primiparous women in Australia rated their parents' attitudes and behaviors toward them as children as well as perceived levels of social support shortly after the birth of their first child and 1 year later. After any bias that might have been introduced by neurotic perception of interpersonal relationships had been controlled for, analyses showed a consistent link over time between reports of perceived deficiencies in both maternal care during childhood and in the availability of close supportive relationships during adulthood. This study supports and extends findings from a 1986 U.S. study. PMID- 3348453 TI - Some correlates of prospectively defined premenstrual syndrome. AB - Correlates of prospectively defined premenstrual syndrome were investigated in 50 women who visited a premenstrual syndrome clinic. To assess premenstrual symptom change relative to daily change, the author used effect size, the difference in mood ratings between the post- and premenstrual phases divided by the standard deviation of the entire cycle. Only 12 women had an effect size greater than or equal to 1.0 in two cycles. The probability of having premenstrual syndrome was positively related to working outside the home and negatively related to age. The results underscore the need to use prospective diagnostic criteria in research on premenstrual syndrome. PMID- 3348455 TI - Ostensible agency: another malpractice hazard. AB - Under the tort doctrine of ostensible (apparent) agency, a psychiatrist was named as a codefendant in a psychiatric malpractice suit against a nonmedical psychotherapist employed in his medical group, who had treated the plaintiff in her private practice in the same offices. The psychiatrist was later dismissed as a defendant, but to avoid being sued in such a case, a psychiatrist contemplating an association with another professional should 1) check the professional's record with the appropriate licensing agency, 2) require proof of licensure and malpractice insurance, 3) require that the professional's private patients sign disclosure statements, and 4) assure that names on written materials are kept separate. PMID- 3348454 TI - A follow-up investigation of offspring of parents with bipolar disorder. AB - Seven male children who each had a manic-depressive parent (five alos had a parent with unipolar depression) and 12 control children were studied. The proband children had shown a range of adjustment problems as infants and toddlers. Four years later, they continued to have substantial behavior problems, including ones that could be classified as DSM-III psychiatric diagnoses. On the basis of psychiatric interviews and psychological assessments, the proband children received more DSM-III diagnoses than the control children. Proband children reported internalizing symptoms; this pattern was corroborated by their mothers, who also characterized these children as showing antisocial behavior patterns. PMID- 3348456 TI - Alternative patterns of seasonal affective disorder: three case reports from north India. AB - Three cases of seasonal affective disorder in north India are described, illustrating different seasonal patterns: 1) mania in summer and depression in winter, 2) mania in early winter and depression in late winter, and 3) depression in summer and mania in early winter. PMID- 3348457 TI - An unusual presentation of vitamin B12 deficiency. PMID- 3348458 TI - Adverse reaction to use of caffeine in ECT. PMID- 3348459 TI - Failure of sleep deprivation to prolong seizures in ECT. PMID- 3348461 TI - Sexual dysfunction related to alprazolam treatment of social phobia. PMID- 3348460 TI - Glutethimide intoxication and withdrawal. PMID- 3348462 TI - Panic attacks and exposure to chemical agents. PMID- 3348463 TI - Amantadine for treatment of cocaine dependence in methadone-maintained patients. PMID- 3348464 TI - Thyroid disease and dementia of the Alzheimer type. PMID- 3348466 TI - The organic mental disorders subsection of DSM-III-R. PMID- 3348465 TI - Lithium and antithyroid antibodies. PMID- 3348467 TI - Immunocompetence during stress. PMID- 3348468 TI - Suicide attempts by high school students. PMID- 3348470 TI - AIDS and public health. PMID- 3348469 TI - Drug side effects and the double-blind design. PMID- 3348471 TI - The impact of AIDS on state and local health departments: issues and a few answers. AB - Owing to large differences in the incidence of AIDS (acquired immunodeficiency syndrome) and in public health resources and priorities, the impact of AIDS on state and local health departments has been variable. Nonetheless, health departments everywhere are being held responsible for surveillance and control of the HIV (human immunodeficiency virus) epidemic which we believe requires, at minimum, convenient, free HIV testing and counseling; expanded HIV services in sexually transmitted diseases clinics and substance treatment centers; locally oriented AIDS information/education; notification of persons unknowingly exposed to HIV; restrictive measures for HIV-infected persons who, after counseling, persist in exposing others; regulation or closure of public establishments in which HIV transmission is likely to result; and confidential reporting of all HIV test results to public health departments. In Colorado new legislation was passed to require reporting of HIV test results, to provide the reports with near absolute protections against unauthorized disclosure, and to modify quarantine statues to incorporate rights to due process, appeals, and confidentially. States in which there is a legal basis for discrimination against gay men will need to rectify this problem first. There is no evidence that reporting of HIV infections in Colorado has adversely affected the rate at which persons with HIV risk behaviors volunteer to be tested. For Denver and Colorado Departments of Health, more than 70 per cent of the estimated $2,796,000 expended in AIDS activities during 1987 was federal. PMID- 3348472 TI - AIDS, policy analysis, and the electorate: the role of schools of public health. AB - Current debates concerning appropriate policy to combat the epidemic of acquired immunodeficiency syndrome (AIDS) have raised critical questions regarding the role that schools of public health and individual public health professionals should play, if any, in AIDS-related policy analysis and social advocacy. In the summer of 1986, the School of Public Health at the University of California at Berkeley initiated a telegram sent by the Deans of all 23 schools of public health to protest US Department of Justice AIDS policy and, in the subsequent fall, the school expanded its public educational role in an unprecedented manner by initiating and issuing, with California's other three schools of public health, a policy analysis of Proposition 64, the LaRouche AIDS Quarantine Initiative. That analysis exposed the proposition's fallacious claims regarding casual transmission of AIDS and served to educate the electorate on the likely public health impact of this deleterious legislation. Based on these experiences, and in light of ongoing national controversy regarding AIDS, we believe schools of public health have an important role to play in policy analysis, and individual public health professionals have a role to play in social advocacy. PMID- 3348473 TI - Geographic distribution of human immunodeficiency virus markers in parenteral drug abusers. AB - Drug abuse treatment programs in six regions of the United States collaborated in a study aimed at monitoring trends in the seroprevalence of human immunodeficiency virus (HIV) antibodies. The wide disparities in HIV seroprevalence in the face of similarities in drug using behavior have important implications for prevention. In the New York City area (Harlem, Brooklyn), 61 per cent of samples (N = 280) obtained in late 1986 were positive, up from 50 per cent of samples (N = 585) in early 1985. In Baltimore, Maryland, 29 per cent of samples (N = 184) representing 11 programs were positive. In contrast, samples from programs distant from the Northeast corridor had far lower rates: Denver, Colorado 5 per cent (N = 100); San Antonio, Texas 2 per cent (N = 106); Southern California, 1.5 per cent (N = 413); and Tampa, Florida, 0 per cent (N = 102). Contrary to expectations, there was no corresponding difference in reported lifetime needle sharing experiences, which ranged from 70 per cent in New York to 99 per cent in San Antonio. HIV seropositivity was associated only with geographic location and ethnicity; however, because needle sharing is practiced by parenteral drug abusers in areas where seroprevalence is still relatively low, these areas are potentially vulnerable to the same catastrophic spread seen in the Northeast. A window of opportunity exists where prompt, vigorous, and aggressive efforts at prevention could have major impact. PMID- 3348475 TI - Sexually active adolescents and condoms: changes over one year in knowledge, attitudes and use. AB - Over a year when public health information regarding AIDS intensified, changes in perceptions and use of condoms in a sample of sexually active adolescents in San Francisco were examined. Although perceptions that condoms prevent sexually transmitted diseases (STDs) and the value and importance placed on avoiding STDs remained high, these were neither reflected in increased intentions to use condoms nor in increased use. PMID- 3348476 TI - Peer review guidelines. PMID- 3348474 TI - Concerns of medical and pediatric house officers about acquiring AIDS from their patients. AB - To assess the degree of house officers' concerns about acquiring AIDS (acquired immunodeficiency syndrome) from their patients, we surveyed 263 medical and pediatric interns and residents in four housestaff training programs affiliated with seven New York City hospitals with large AIDS patient populations; 258 questionnaires (98 per cent) were returned. Thirty-six per cent of medical and 17 per cent of pediatric house officers reported percutaneous exposures to needles contaminated with blood of AIDS patients. Forty-eight per cent of medical and 30 per cent of pediatric house officers reported a moderate to major concern about acquiring AIDS from their patients. Greater concern about personal risk was noted in those house officers who were earlier in their residency training, who reported having treated a greater number of AIDS patients, and who were in medicine rather than pediatrics programs. Twenty-five per cent of all respondents reported that they would not continue to care for AIDS patients if given a choice. The results demonstrate a substantial degree of concern about acquiring AIDS among house officers caring for AIDS patients and suggest the need for housestaff program administrators for formally address these concerns. PMID- 3348477 TI - Determination of dihydroqinghaosu in blood by pyrolysis gas chromatography/mass spectrometry. PMID- 3348478 TI - Determination of cephalosporins and decomposition products by liquid chromatography with indirect electrochemical detection. PMID- 3348479 TI - Measurement of liposome-released ferrocyanide by a dual-function polymer modified electrode. PMID- 3348480 TI - Simultaneous determination of glucose, fructose, and sucrose in mixtures by amperometric flow injection analysis with immobilized enzyme reactors. PMID- 3348481 TI - Influence of porphyrin structure on anion selectivities of manganese(III) porphyrin based membrane electrodes. PMID- 3348482 TI - Fabrication of platinum-disk ultramicroelectrodes. PMID- 3348483 TI - Phorbol ester stimulates macrophage invasion of fibrin matrices. AB - Macrophages migrate through a fibrin-rich extracellular matrix in chronic inflammation, wound healing, and other pathophysiological processes. To investigate the factors that might influence the ability of mononuclear phagocytes to invade fibrin matrices, we cultured macrophage-like P388D1 cells as well as resident and thioglycollate-elicited mouse peritoneal macrophages on three-dimensional fibrin gels, and we examined the effect of agents known to stimulate a variety of macrophage functions, including the production of fibrinolytic enzymes. Cells grown on fibrin gels under control conditions, as well as cells treated with either bacterial lipopolysaccharide or concanavalin A, remained confined to the gel surface. In contrast, the tumor promoter 4 beta phorbol 12-myristate 13-acetate (PMA) induced both P388D1 cells and peritoneal macrophages to invade the underlying fibrin matrix. The invasive behavior of PMA treated P388D1 cells was not affected by protease inhibitors of various specificities. These results demonstrate that certain exogenous signals can profoundly modify the ability of macrophages to migrate through fibrin matrices. PMID- 3348484 TI - Further observations on the sympathetic pathways to the pupil. AB - The clinical disturbance resulting from section of the sympathetic in the neck; miosis, decreased sweating, increased vascularity and narrowing of the palpebral fissure is universally recognized while the definitive sympathetic pathways remain unknown. Most current texts depict a plexus along the surface of the parasellar carotid as part of that pathway although a previous review leaves the large connection of the carotid sympathetic to the sixth and then to the first division of the fifth cranial nerve as a putative pathway. Recent reports of complete tears of the parasellar carotid without sympathetic changes tend to further discount a carotid plexus as a pathway and focus attention on the direct carotid sympathetic nerve connections to the sixth and fifth cranial nerves as probable but unproven pathways, the interruption of which, result in Bernard, Mitchell, Horner Syndrome. (Parkinson '79). PMID- 3348485 TI - Development of preimplantation rabbit embryos after in-vitro culture and embryo transfer: an electron microscopic study. AB - Compared to in vivo development, in vitro culture of mammalian embryos results in developmental retardation. To study the potential of reversibility of growth retardation we investigated ultrastructurally day 3 rabbit embryos after 1 day in vitro, and cultured embryos that were transferred after culture into recipient rabbits for 1 day. Morphology was compared with ultrastructure of noncultured controls. The noncultured embryos were compacted morulae; the characteristic ultrastructure is described in detail. After 1 day in culture, morulae had developed into early blastocysts. However, unlike the results in vivo, expansion of the blastocysts did not occur and some of the cultured embryos developed trophoblast herniations. In all cultured embryos morphological signs of degeneration were seen with swollen mitochondria, with a dense, granular appearance of the cytoplasm, and with an increase in number of lysosomes. Transfer of cultured blastocysts into uteri of day 3 pseudopregnant recipients resulted in ultrastructurally intact and expanded blastocysts. Transfer into uteri of day 4 pseudopregnant recipients and into uteri of nonpregnant recipients, however, did not yield reversibility of the unphysiological features suffered during the previous time in culture. Although blastocysts were well expanded, distinct signs of injury to the blastomeres were present, proceeding from loss of complete blastomeres to structural changes such as large lamellar structures, dilation of smooth endoplasmic reticulum and Golgi complexes, and clumping of mitochondria. We conclude that developmental retardation during in vitro culture is accompanied by distinct morphological changes. As soon as 24 hr after transfer, these changes can be reversed. This compensation, however, is achieved only if embryos are transferred into recipients that are adapted to the embryo's developmental stage, which is not identical to the embryo's chronological age. Our findings demonstrate that the period of 24 hr of in vitro development matches only a few hours of in vivo development. PMID- 3348486 TI - Maturation changes of the plasma membrane of rat spermatozoa observed by surface replica, rapid-freeze and deep-etch, and freeze-fracture methods. AB - Rat spermatozoa from the epididymis and ductus deferens were observed by surface replica, rapid-freeze and deep-etch, and conventional freeze-fracture methods. By the surface replica method, parallel periodical ridges were observed in the acrosomal region of the spermatozoa from the distal part of the cauda epididymis (zone 6) and from the ductus deferens. The periodicity of the ridges forming a domain was about 35 nm. A quantitative analysis of the spermatozoa along the reproductive tract indicated that 39.4% and 73.5% of the population in zone 6 of the epididymis and in the ductus deferens, respectively, had the domain. None of the spermatozoa from zone 1 through zone 5 had the domain. The results of the rapid-freeze and deep-etch procedure showed that the ridges observed by the surface replica method consisted of linear arrangements of elliptical particles on the ES face of the plasma membrane. The particles were about 30 nm in length and 15 nm in width. On the corresponding PF face of the plasma membrane, linear arrangements of the intramembrane particles (IMPs) of about 8 nm in diameter were observed by both the deep-etch and freeze-fracture methods. The IMPs tended to run in paired parallel lines. A close relationship was observed between the lines of the elliptical particles on the ES and of the IMPs on the PF faces. The elliptical particle may be a protruded part of the IMP(s) or other protein(s) bound to the IMP(s). PMID- 3348487 TI - The ductuli efferentes of the goat: a morphological study. AB - The morphology of the ductuli efferentes of the goat was compared with that of other animal species, especially with that of the bull. Both in the goat and in the bull, it forms a slightly brownish, bulbous mass of highly convoluted ductules (18-19 in the goat, 13-16 in the bull) that occupies approximately one third of the first limb of the caput epididymidis. The epithelium consists of two major cell types, ciliated and nonciliated, and a few intraepithelial lymphocytes and macrophages. The nonciliated cells can be further divided into three types: type II cells are characterized by specific granules that are dense, mostly homogeneous, eosinophilic, osmiophilic, and positive to periodic acid-Schiff (PAS) staining; type III cells are characterized by specific vacuoles that appear empty and do not stain with PAS, eosin, or osmium; type I cells lack both granules and vacuoles. These morphological, histochemical, and tinctorial differences observed among nonciliated cell types suggest that they are probably independent cell types rather than functional stages of one cell type. All three cell types are endowed with absorptive features such as microvilli, pinocytotic vesicles, and subapical vacuoles, but a higher differentiation of these features in type III cells suggests their greater role in the absorption of testicular fluid. Whether granules of type II cells and vacuoles of type III cells are absorptive and/or secretory remains unresolved from the available data. However, some circumstantial evidence, as presented in the discussion, supports the latter possibility. PMID- 3348488 TI - Basal lamina fenestrations in the human colon: transmission and scanning electron microscope study. AB - Basal lamina at the interface between colonic epithelial cells and the lamina propria was exposed by incubating colonic specimens in 1% boric acid solutions. Examination of this epithelial-stromal interface by scanning electron microscopy (SEM) showed a smooth, slightly undulating basal lamina covering crypts and luminal surfaces. The basal lamina on the luminal surfaces had numerous round or ovoid fenestrations, most measuring 2.5-4.0 microns. These were continuous with channels in the collagen fiber network of the lamina propria. Except very near the surface, no fenestrations were found in the basal lamina lining the crypts. Transmission electron microscopy (TEM) of serial thin sections of colonic mucosa without the epithelial cells removed showed only a few actual basal lamina fenestrations. Rarely, epithelial cell processes extended into the lamina propria through the basal lamina. Most of the fenestrations seen by SEM appeared to correspond spatially by TEM to foci of close contact between the basal lamina and underlying fibroblastic cell processes. At these sites the basal lamina and fibroblastic cell process might be removed along with the overlying epithelial cells during processing with boric acid. These data support functional differences in epithelial-stromal interaction between cell populations lining the luminal surface and those making up the crypt lining and pericryptal fibroblast sheath. The TEM findings demonstrate that the human colonic basal lamina is not absolutely continuous and that the development of basal lamina fenestrations and epithelial cell processes extending into the lamina propria is not pathognomonic of neoplastic transformation and stromal invasion. PMID- 3348489 TI - A reexamination of the role of microfilaments in neurulation in the chick embryo. AB - Formation of wedge-shaped neuroepithelial cells, owing to the constriction of apical bands of microfilaments, is widely believed to play a major part in bending of the neural plate. Although cell "wedging" occurs during neurulation, its exact role in bending is unknown. Likewise, although microfilament bands occupy the apices of neuroepithelial cells, whether these structures are required for cell wedging is unknown. Finally, although it is known that cytochalasins interfere with neurulation, it is unknown whether they block shaping or furrowing of the neural plate, or elevation, convergence, or fusion of the neural folds. The purpose of this study was to reexamine the role of microfilaments in neurulation in the chick embryo. Embryos were treated with cytochalasin D (CD) to depolymerize microfilaments and were analyzed 4-24 hr later. CD did not prevent neural plate shaping, median neural plate furrowing, wedging of median neuroepithelial cells, or neural fold elevation. However, dorsolateral neural plate furrowing, wedging of dorsolateral neuroepithelial cells, and convergence of the neural folds were blocked frequently by CD. In addition, neural folds always failed to fuse across the midline in embryos treated with CD, and neural crest cell migration was prevented. These data indicate that only the later aspects of neurulation may require microfilaments, and that certain neuroepithelial cells, particularly those that normally wedge with median furrowing and elevation of the neural folds, become (and remain) wedge-shaped in the absence of apical microfilament bands. Thus, microfilament-mediated constriction of neuroepithelial cell apices is not the major force for median neuroepithelial cell wedging and elevation of the chick neural plate. Further studies are needed to localize the motor(s) for these processes. PMID- 3348490 TI - High 2,3-DPG blood cardioplegia and myocardial preservation during cardiopulmonary bypass. AB - Blood may provide superior cardioplegia compared with crystalloid cardioplegic solution. However, the results are controversial. This may be due to a leftward shift of the hemoglobin (Hb)-O2 dissociation curve induced by hypothermia, increasing the oxygen affinity for Hb. This effect may negate the potential benefit of blood cardioplegia. The oxygen affinity for Hb can be decreased by increasing the red cell 2,3-diphosphoglycerate (2,3-DPG), and hence, more oxygen can be delivered to the myocardium. The present investigation was undertaken to study the effects of 2,3-DPG-enriched blood cardioplegia on the functional recovery of the myocardium and changes in the coronary sinus red blood cell (RBC) adenosine-triphosphate (ATP), lactate, and RBC DPG after one and a half hours of reperfusion following one hour of ischemic cardiac arrest in dogs. The dogs were divided into three groups: crystalloid (CR); stored blood (SB), and high 2,3-DPG blood (HDPG) cardioplegic groups. Incubation of canine RBC in phosphoenal pyruvate (PEP) led to a 36% increase in DPG and a rightward shift in the Hb-O2 dissociation curve. There was a 4 mm Hg shift in the P50. When compared with the CR group, there was a significant decrease in the cardiac index (CI) and left ventricular work index (LVWI) and a significant increase in the total systemic vascular resistance (TSVR) in the SB group. The CI and LVWI of the HDPG group were similar to those of the CR group, but the TSVR was significantly greater in the former group. The LVWI was significantly greater and the TSVR smaller in the HDPG group as compared with those in the SB group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348491 TI - Coronary angiography of Kawasaki disease with the coronary vasodilator dipyridamole: assessment of distensibility of affected coronary arterial wall. AB - The authors evaluated the distensibility of the coronary arterial wall by pharmacoangiography with intravenous administration of dipyridamole in 38 patients with Kawasaki disease. In the acute stage of the illness, the coronary arteries were evaluated for aneurysms by two-dimensional echocardiography. After the acute stage of the illness, selective coronary cineangiographies were performed by Seldinger's method under general anesthesia before and after intravenous administration of 0.6 mg/kg of dipyridamole for four minutes. The calibers of aneurysms and normal appearing segments of coronary arteries, at most 7 segments in 1 patient, were measured before and after dipyridamole administration on the high-quality cineangioanalyzer and percentages of coronary arterial dilatation were calculated. In 14 cases without evidence of coronary arterial lesions, the distensibility was 10.2 +/- 4.7% (mean +/- SD). The distensibility of 32 aneurysms in 16 cases was 0.6 +/- 1.1% and was significantly decreased (p less than 0.001). In 24 cases with coronary arterial lesions, aneurysms, stenosis, or obstruction, the distensibility of normal appearing segments of coronary arteries was 4.5 +/- 4.9% and was significantly decreased (p less than 0.001). This method is useful in evaluating distensibility and appears to be effective in detecting pathologic changes of the coronary arterial wall, even if it appears normal in shape. The patient with previously diseased coronary arteries should be kept under careful longterm surveillance. PMID- 3348492 TI - Elephantiasis nostras--a case report. AB - Elephantiasis nostras, the result of chronic lymphedema, is characterized by marked edema of the affected extremity with a thickened, verrucous, pebbly appearance of the skin. The pathogenesis is thought to be related to fibroblast proliferation following impaired lymphatic drainage, leading to fibrosis and further restriction of lymph drainage with progressive edema. A case report of a patient with massive chronic lymphedema of her feet is presented. PMID- 3348493 TI - Left ventricular thromboembolic occlusion of the popliteal artery treated nonoperatively with local urokinase infusion--a case report. AB - Recently streptokinase and urokinase have been shown to be useful in the nonoperative treatment of thromboembolic disease. Urokinase is emerging as a safer and more effective thrombolytic agent when applied either to definitively lyse spontaneous thrombosis where no underlying structural lesion is present or to serve as an adjunct prior to surgical reconstruction or transluminal angioplasty. The authors report a case of a high-risk cardiac patient in whom an embolic occlusion of the distal popliteal artery was completely recanalized by using a localized catheter infusion of urokinase. The source of the embolus was a left ventricular thrombus. No serious bleeding or proximal or distal embolic complications occurred. The potential hazards of fragmentation of the embolic source in the presence of systemic thrombolysis, distal trifurcation embolization, and concomitant use of heparin are reviewed. PMID- 3348494 TI - An autopsied case of systemic lupus erythematosus with pulmonary hypertension--a case report. AB - The authors report an autopsied case of systemic lupus erythematosus (SLE) with pulmonary hypertension. The patient was a forty-five-year-old female who had been troubled by obstinate Raynaud's phenomenon for ten years before the definite diagnosis of pulmonary hypertension was made. Microscopic examination of the pulmonary vasculature yielded findings consistent with plexogenic pulmonary arteriopathy. However, the deposition of immune complexes in the pulmonary vascular endothelium was not detected by enzyme antibody study. This case suggests, therefore, that "pulmonary Raynaud's phenomenon" is a possible pathogenesis of pulmonary hypertension in patients with SLE. PMID- 3348495 TI - Recurrent otitis media, sinusitis and pulmonary infiltrates in a 13-year-old girl. PMID- 3348497 TI - Urticaria caused by caffeine. PMID- 3348496 TI - Lymphocytic interstitial pneumonia of common variable immunodeficiency. AB - We report the beneficial effect of steroids in a 27-year-old woman with lymphocytic interstitial pneumonitis (LIP) and common variable immunodeficiency (CVID). Exertional dyspnea, x-ray infiltrates, and pulmonary physiologic abnormalities decreased or increased during 3 1/2 years of follow-up in parallel with the administered dose of prednisone. This observation rules out concomitant spontaneous remission as the explanation of steroid-induced improvement of LIP in CVID. Steroid treatment was apparently safe: the frequency and severity of recurrent bronchial infections did not change, although IgG replacement therapy was not provided. PMID- 3348498 TI - Occupational asthma due to frogs. PMID- 3348499 TI - Comparison of alum-precipitated aqueous extracts and modified ragweed tyrosine adsorbate vaccine in the treatment of ragweed hay fever. AB - Thirty-five ragweed-sensitive patients received immunotherapy with either alum precipitated aqueous extracts (AP) or modified ragweed tyrosine adsorbate vaccine (Pollinex-R). Symptoms decreased with AP therapy only. Immunologically, there was a blunted specific IgE response and little specific IgG increase associated with both groups. Alum-precipitated aqueous extracts appeared to be more efficacious than Pollinex-R. PMID- 3348500 TI - Effects of inhaled humidified warm air on nasal patency and nasal symptoms in allergic rhinitis. AB - The effects of inhaled warm air on nasal patency and on allergic rhinitic symptoms were studied in 102 patients. Treatment consisted of two consecutive 30 minute sessions, during which the patient inhaled saturated, hot (42-44 degrees C) air through the nose. The treatment was repeated 1 week later. During the week following each treatment, every patient recorded his or her subjective response on a daily symptom score card. Nasal patency was determined before and after each treatment by measuring peak nasal inspiratory and expiratory air flow and by measuring the area covered with vapor formed by the exhaled air on a plate. Highly reproducible results were obtained by using these three objective methods. Inhalation of humidified warm air resulted in amelioration of allergic rhinitis symptoms and in increased nasal patency in a high proportion of patients. There were no adverse side effects. This form of therapy seemed effective in the 2-week period in which it was used and would be an additional form of therapy available for those suffering discomfort from allergic rhinitis. PMID- 3348501 TI - Natural killer cell activity in specific and non-specific bronchial challenge. AB - In specific bronchial challenge with birth, mugwort, or timothy pollen, five asthmatics showed a significant increase in peripheral blood natural killer (NK) activity in conjunction with bronchoconstriction. In non-specific bronchial challenge with histamine, four patients showed a significant initial decrease of NK activity followed by a later augmentation of reactivity. The later boost of NK activity was detectable also a trend in specific bronchial challenge. No significant changes of NK activity were observed during control days when no bronchial challenges were performed. The results indicate that pulmonary hypersensitivity reactions are associated with augmentation of NK activity. PMID- 3348502 TI - Annual variation of Cladosporium spores in home habitats in Cordoba, Spain. AB - We have studied the annual variation of the concentration of Cladosporium spores in three different types of rooms in 14 homes in the city of Cordoba, Spain. Ten species have been isolated, some of which are potentially allergenic. The results also show certain correlations between the concentration of spores and climatic factors, and only small differences between the flora identified in the different rooms. PMID- 3348503 TI - Corticosteroid complications in respiratory disease. PMID- 3348504 TI - The slow response to therapy in a patient with multiple admissions for bronchial asthma. PMID- 3348505 TI - Chronic asthma and rhinitis due to Candida albicans. PMID- 3348506 TI - Viability of live viri in re-used syringes with different needles. PMID- 3348507 TI - Immunologic and atopic aspects of pregnancy and lactation. PMID- 3348508 TI - Sweat sodium levels in adults with nasal polyps. PMID- 3348509 TI - Problems with generic theophylline and indiscriminate brand switching. PMID- 3348510 TI - [Auditory evoked potentials of the brain stem in brain death]. AB - Brainstem auditory evoked responses were recorded in a neurosurgical intensive care unit in 38 patients who had all the clinical criteria for brain death. Of the brain-dead patients, 65.8% never showed a response. 3.42% showed a type I wave, which was unilateral in 26.3% and bilateral in the other 7.9%. Types II to VII waves were never seen. An increase in latency of type I waves (2.25 +/- 0.24 ms) was noted. The interest and the limits of this non invasive electrophysiologic technique for the diagnosis of brain death are discussed. PMID- 3348511 TI - [Secondary lung diseases in patients with nasotracheal intubation. Role of nosocomial sinusitis]. AB - Nosocomial pneumonia is a frequent infectious complication in ICU patients. All the patients with prolonged nasotracheal intubation presenting with nosocomial pneumonia according to Salata's criteria were examined for sinusitis in the prospective study. Diagnosis was confirmed via CT-scan views and transnasal sinus puncture. In eleven nasally intubated patients, CT-scan views showed air fluid levels and multiple sinus involvement. Bacteriological studies isolated the same gram negative bacilli in both sinus and bronchial aspirates. In four cases, a polymicrobial sinusitis was found with a single organism predominant. This predominant germ was always found in bronchial aspirate. Recovery from pneumonia was obtained only after sinus drainage. Treatment included removing the nasal tubes, or performing tracheostomy and systemic antibiotics. One patient required surgical maxillary sinus drainage after failure of medical management. The occurrence of nosocomial pneumonia in nasotracheally intubated patients should lead physicians to explore the paranasal sinuses. Sinus CT-scan views should be routinely obtained in the assessment of pulmonary sepsis in patients with prolonged nasotracheal intubation. Persistent or ignored nosocomial sinusitis in such circumstances could be a major source of treatment failure. PMID- 3348512 TI - [Regional anticoagulation with citrate in hemodialysis in patients with a high risk for hemorrhage]. AB - During haemodialysis in the patient at high risk for bleeding, heparin cannot be safely used to prevent clotting in the dialysis assembly. Among numerous procedures proposed to reduce the risk for bleeding, Pinnick et al. (N Engl J Med, 308: 258, 1983) proposed the use of citrate as the sole anticoagulant. Citrate toxicity and efficiency were studied during 44 haemodialyses carried out in thirteen patients with a high risk for bleeding or with active bleeding. Three patients had hepatic failure. Two types of citrate solution were used, the trisodium form of citrate (102 mmol.l-1 citrate) or the monosodium form (306 mmol.l-1 citrate). The solutions were infused with a calibrated, pressure insensitive pump, before the dialysis unit at a flow rate of 600 ml.h-1 and 200 ml.h-1 respectively. Sufficient citrate was infused to maintain a clotting time of the blood line and dialyser of more than 18 min. Standard 10% calcium chloride was infused at a constant rate of 7 mg.min-1 into the blood being returned to the patient. The patients were dialysed for 4 h for each haemodialysis with a single pass system. The dialyses were uncomplicated; no active bleeding was noted. The patient's clotting time was significantly reduced during haemodialysis (18.1 +/- 8.9 min to 14.5 +/- 6.3 min; p less than 0.001). Two-hundred and twenty serum citrate levels were measured. Only nine were above the toxic value of 2 mmol.l-1. No clinical evidence of a decrease in ionized calcium was found: there was no change in the corrected QT intervals and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348514 TI - [Value of transcutaneous blood gas monitoring in fiberoptic bronchoscopy in intensive care patients]. AB - Transcutaneous carbon dioxide and oxygen tensions (PtcCO2 and PtcO2) were monitored in seven critically ill patients under mechanical ventilation during fiberoptic bronchoscopy. In these conditions, both PtcO2 and PaO2 and PtcCO2 and PaCO2 correlated, with correlation coefficients of 0.964 and 0.793 respectively. Fiberoptic bronchoscopy induced an average fall in PtcO2 of 42 +/- 2.57 mmHg and an average increase in PtcCO2 of 12.1 +/- 1.89 mmHg; these two parameters returned quickly to their initial values after the procedure. Holter monitoring showed an arrhythmia in five of the seven patients. Continuous measurement of PtcO2 and PtcCO2 was a safe and reliable method for monitoring mechanically ventilated patients undergoing fiberoptic bronchoscopy. PMID- 3348513 TI - [Carotid endarterectomy under cervical epidural anesthesia. Analysis of neurologic manifestations]. AB - Carotid endarterectomy can be complicated by neurological events due to different mechanisms. Monitoring cerebral function is difficult under general anaesthesia. By contrast, the monitoring of awareness and neurological deficit is very easy under regional anaesthesia. The aim of this study was to assess the requirement for arterial shunting during endarterectomy performed under cervical epidural anaesthesia, to analyse the neurological events and to compare the value of clinical and electroencephalographic monitoring. Sixty-four patients were included in this study. Cervical epidural anesthesia was performed with 0.375% bupivacaine and 100-150 micrograms fentanyl. In 19 high risk patients, a one channel electroencephalographic filter processor (Cerebral function monitor, Critikon) was placed over the affected hemisphere. Before surgery, it was estimated, on angiographic and Doppler data, that 18 patients needed an arterial shunt for carotid clamping. An arterial shunt was in fact inserted during surgery in only four patients, because of cerebral ischaemia after carotid clamping. Transient obnubilation was observed during carotid clamping in three other patients; it disappeared on unclamping in two, and on increasing blood pressure in the third. An additional patient suffered from a very short loss of awareness after declamping, due to cerebral embolism. The cerebral function monitor never documented false positive results, but failed to detect one out of every five neurological events. Controlateral carotid occlusion and preoperative stroke were documented to correlate with peroperative neurological events. Cervical epidural anaesthesia, which maintains consciousness during surgery, reduced in high-risk patients the need for arterial shunting as well as that for the analysis of neurological events. PMID- 3348515 TI - [Magnetic resonance imaging: potential risks and requirements for monitoring choice]. PMID- 3348516 TI - [Multiple sclerosis disclosed by spinal anesthesia]. AB - A case is reported of an acute onset of previously undiagnosed multiple sclerosis, revealed by an oculomotor paralysis following spinal anaesthesia performed for minor orthopaedic surgery. The need for a complete preoperative physical examination is underlined by this case, looking for latent neuromuscular disorders before undertaking such techniques, and for a thorough neurological work-up should such a complication arise. The harmlessness of regional anaesthesia in multiple sclerosis patients is controversial; without entering into such a debate, the direct relationship between spinal anaesthesia and acute exacerbation of the disease in our patient seemed more than likely. PMID- 3348517 TI - [Continuous inflation of a leaking cuff of an intubation tube]. AB - Perforation of the cuff of the endotracheal tube peroperatively is a very serious problem, especially when it occurs in a patient prone on an orthopaedic table. This is even more dramatic when the patient is not breathing spontaneously and he cannot be turned over to be reintubated. Given the unusual character of this situation, an apparatus has been designed to keep the cuff inflated permanently. It was a circuit consisting of a manual pressure valve, flexible tubing, a peripheral catheter and the cuff supply tube. The gas used was medical air at 3 bar pressure. This method proved perfectly safe and efficient, the operation having continued without reintubation. PMID- 3348518 TI - [Severe hypophosphoremia in a toxic shock syndrome]. AB - A case of toxic shock syndrome occurring during a menstrual period, and associated with severe hypophosphataemia, is reported. The patient was a 21-year old woman using tampons. On the fourth day, she developed encephalopathy with decreased consciousness and hyperventilation. Severe hypophosphataemia was noted. A phage-group-1 Staphylococcus aureus, producing TSST-1 and enterotoxin A, was isolated from vaginal, pharyngeal and skin sites. Pathogenesis and role of hypophosphataemia in toxic shock syndrome are emphasized. PMID- 3348519 TI - [Surface changes of intravenous catheters after antineoplastic chemotherapy]. AB - During long-term venous catheter implantation, septic and thrombotic complications are quite frequent. In the case reported, the failure of systemic and local antibiotic therapy during repeated septicaemia due to Bacillus cereus at the time of intensive chemotherapy led to a scanning electron microscopy study of the used silicone catheter. There were marked changes of the inner surface with a lot of cellular remains, in contrast with the usual non thrombogenic property of the silicone. An in vitro study was carried out with antitumour agents. Duration of exposure and drug concentration were identical to those used in in vivo perfusions. There were marked changes of the inner surface, which could lead to important modifications of the properties of the silicone. The damage depended on the drug. Silicone was slightly sensitive to vicristin and carmustin, but highly sensitive to cisplatin and doxorubicin. The compatibility of catheter material with the drugs used, especially for oncologic chemotherapy, must be tested systematically. PMID- 3348520 TI - [Continuous monitoring, in the adult, of arterial oxygen saturation during apnea following intubation]. AB - Twenty ASA I or II patients were studied to assess the safety of oxygenation for 4 min prior to intubing, so as to prevent the hypoxaemia related to tracheal intubation. The arterialized capillary blood saturation (Spo2) was continuously monitored with a pulse oximeter Nellcor 100 equipped with a finger probe. Patients spontaneously breathed oxygen (FIO2 = 1) while anaesthesia was induced with pancuronium bromide, thiopentone and fentanyl. Following apnoea, ventilation was manually controlled during 4 min (FIO2 = 1). The values of Spo2 were recorded before induction, at the end of the 4 min oxygenation period and after 5 min of apnoea. An arterial blood sample was withdrawn at the end of apnoea and analysed immediately using an OSM 2b hemoximeter. Apnoea was interrupted in case of desaturation below 95%, new arrhythmia or haemodynamic instability (blood pressure +/- 20% of control value). Mean saturation (+/- SD) before oxygenation was 98.6 +/- 1.35%. After oxygenating for 4 min, all the Spo2 reached 100%. After the 5 min apnoea period, no saturation was below 95% (mean +/- SD = 98.89 +/- 1.66); at this time, Sao2 and Spo2 did not significantly differ (p less than 0.001). In one case, apnoea had to be interrupted, because of the occurrence of arrhythmias, unrelated to a blood gas disorder (PaO2 = 225 mmHg; Paco2 = 34 mmHg; SaO2 = 100%; pH = 7.44). This study confirmed the efficacy and safety of oxygenating for 4 min before intubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348521 TI - [Intrathecal tolerability of midazolam. Histological study]. PMID- 3348522 TI - [1988: at last, non-interchangeable bottles for nitrous oxide!]. PMID- 3348524 TI - [Anesthesia for bronchial carcinoma in a multiple injured patient]. PMID- 3348523 TI - [Peroperative circulatory arrest after intravenous injection of erythromycin lactobionate]. PMID- 3348525 TI - Circulating immune complex concentrations in selected cases of skin disease in dogs. AB - Serum samples from 25 clinically normal dogs and 137 base-line serum samples from dogs with skin disease were assayed blindly for presence of circulating immune complexes (CIC). The method used was a solid-phase C1q-binding enzyme-linked immunosorbent assay. This assay detected only IgG-containing CIC that were capable of binding C1q. Statistical analysis revealed that dogs with systemic lupus erythematosus, discoid lupus erythematosus, generalized demodicosis, and recurrent staphylococcal pyoderma had significantly higher mean CIC concentrations than did normal dogs. Dogs with other skin diseases had mean CIC concentrations indistinguishable from those of normal dogs. Presence of CIC in dogs with these dermatopathies may have pathogenetic significance or may be the result of the disease process. Further studies are necessary to define the antigens contained in the immune complexes and the importance of CIC in skin disease of dogs. PMID- 3348526 TI - Enzyme-linked immunosorbent assay for the detection of antibodies to the alcelaphine herpesvirus of malignant catarrhal fever in exotic ruminants. AB - An ELISA for antibodies to the alcelaphine herpesvirus-1 of malignant catarrhal fever was developed. Of sera that represented 42 exotic ruminant species, 216 were evaluated by the ELISA and a virus-neutralization test. A significant correlation (r = 0.564, P less than 0.001, n = 216) between the ELISA and virus neutralization test results was found. Of the sera having positive test results by virus neutralization, 86.1% also had positive results by the ELISA, and of the sera having negative test results by virus neutralization, 83.9% also had negative results by the ELISA. The presence of antibody, as measured by the ELISA, correlated with clinical signs of malignant catarrhal fever and the isolation of herpesvirus. PMID- 3348527 TI - Oral administration of an attenuated strain of canine adenovirus (type 2) to raccoons, foxes, skunk, and mongoose. AB - An attenuated strain of canine adenovirus type-2 (CAV-2) was administered orally to 2 foxes (Vulpes fulva), 6 raccoons (Procyon lotor), a skunk (Mephitis mephitis), and a mongoose (Herpestus auropunctatus). Blood was collected weekly from the animals to monitor CAV-2 virus-neutralizing antibody titers. All animals had increases in titers. Sera from 8 foxes, 30 mongooses, 52 raccoons, and 22 skunks trapped in the field had naturally occurring antibody to CAV-2. PMID- 3348528 TI - Effect of transport on feeder calves. AB - One hundred fifty feeder steers (mean body weight, 195 kg) were assigned to 1 of 3 transport groups and were deprived of feed and water (fasted) for 24 hours. Additionally, calves were transported on a commercial livestock trailer for 0 (control-fasted only), 12 (short haul), or 24 (long haul) hours. Blood samples were obtained from the jugular vein before calves were loaded on the transport vehicle and immediately after calves of the long-haul group returned to the research feedlot. Complete blood counts were performed and 32 mineral, enzyme, and biochemical constituents were measured. Calf morbidity, mortality, and average daily weight gain were evaluated during the next 56 days. Duration of transport did not affect average daily gain; however, calves of the short-haul group had significantly (P less than 0.05) higher morbidity and mortality than did those of the control and long-haul groups. In all groups, results of differential leukocyte counts were indicative of stress response. Significant (P less than 0.05) linear contrasts were observed between duration of transport and erythrocyte, leukocyte, segmented neutrophil, lymphocyte, and eosinophil counts and results of serum enzyme (alanine transaminase, hydroxybutyrate dehydrogenase, total lactate dehydrogenase [LD], and LD-1, LD-3, and LD-4 isoenzymes), iron, urea nitrogen, beta-globulin, glucose, and urea nitrogen-to-creatinine ratio determinations. Significant (P less than 0.05) quadratic contrasts were observed between duration of transport and serum unsaturated iron binding capacity, total iron binding capacity, and LD-5 percentage. Calf source had a significant (P less than 0.05) effect on almost all variables tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348529 TI - Anal sphincter pressure and the rectosphincteric reflex in the dog. AB - Anal sphincter pressure (ASP) was measured in healthy conscious dogs, and the rectosphincteric reflex that causes inhibition of the internal sphincter was identified. Pressures were measured in 6 dogs by use of a perfused miniature 4 lumen catheter. To identify the rectosphincteric reflex, a balloon (fitted over the distal opening of the catheter) was insufflated with 25 ml of air. Mean (+/- SE) ASP was 74.7 +/- 4.2 mm of Hg. When the rectosphincteric reflex was stimulated by balloon distension, ASP decreased to 35.9 +/- 4.9 mm of Hg. The reduction in pressure persisted for 22 +/- 1.5 s, and ASP returned to predistension values, despite the maintenance of balloon distension. Atropine did not affect ASP or its reduction during balloon distension. PMID- 3348530 TI - Predictive value of tracer studies for 131I treatment in hyperthyroid cats. AB - In 76 cats with hyperthyroidism, peak thyroidal radioiodine (131I) uptakes and effective half-lives were determined after administration of tracer and therapeutic activities of 131I. In 6 additional hyperthyroid cats, only peak thyroidal uptakes after administration of tracer and therapeutic activities of 131I were determined. Good correlation was found between peak thyroidal uptakes of tracer and therapeutic 131I; however, only fair correlation was observed between effective half-lives. In 79% of the cats, the effective half-life for therapeutic 131I was longer than that for tracer 131I. After administration of therapeutic activity of 131I, monoexponential and biphasic decay curves were observed in 51 and 16 cats, respectively. Using therapeutic kinetic data, radiation doses to the thyroid gland were calculated retrospectively on the basis of 2 methods for determining the activity of 131I administered: (1) actual administration of tracer-compensated activity and (2) hypothetic administration of uniform activity (3 mCi). Because of the good predictive ability of tracer kinetic data for the therapeutic kinetic data, the tracer-compensated radiation doses came significantly (P = 0.008) closer to the therapeutic goal than did the uniform-activity doses. In addition, the use of tracer kinetic information reduced the extent of the tendency for consistently high uniform-activity doses. A manual method for acquiring tracer kinetic data was developed and was an acceptable alternative to computerized techniques. Adoption of this method gives individuals and institutions with limited finances the opportunity to characterize the iodine kinetics in cats before proceeding with administration of therapeutic activities of 131I. PMID- 3348531 TI - Serodiagnosis of Histophilus ovis-associated epididymitis in rams. AB - An ELISA for the detection of antibodies to Histophilus ovis was used to evaluate the association of epididymal lesions in rams with serologic response to His ovis. Comparison of ELISA results for His ovis in groups of rams with epididymal lesions with ELISA results of clinically normal rams (control group) revealed a significant difference (P less than 0.01) between the control group and those rams from which His ovis was isolated. A significant difference (P less than 0.01) was noticed between the control group and rams with lesions from which an organism other than His ovis or Brucella ovis was isolated. Additionally, a significant difference (P less than 0.01) was noticed in ELISA results between the control group and affected rams from which no organism was recovered and in which the epididymal lesion was not limited to the head of the epididymis. A difference was not detected in the His ovis ELISA results between control rams and rams with lesions associated with a B ovis infection or rams from which no organism was recovered and in which the epididymal lesion was limited to the head of the epididymis. The serologic findings in our study suggest that His ovis is more important in the development of epididymitis in rams than culture results alone would indicate. PMID- 3348532 TI - Hematologic and serum biochemical alterations associated with multiple halothane anesthesia exposures and minor surgical trauma in horses. AB - Five horses were anesthetized similarly by use of xylazine, guaifenesin, thiamylal sodium, and halothane in oxygen on 3 consecutive days, and minor surgical procedures were performed. For 1 to 10 days after the last anesthetic exposure, clinical, hematologic, and serum biochemical features were monitored, and after necropsy, histologic examination of major organ tissues was performed. Predominant hematologic changes from base-line values included leukocytosis (maximal at 27 hours, 10,500 +/- 1,750 cells/microliter), neutrophilia (maximal at 51 hours, 7,485 +/- 1,719 cells/microliter), and lymphopenia (minimal at 51 hours, 1,636 +/- 564 cells/microliter). Alterations observed in other clinicopathologic features were minor and indicative of mild renal disturbance and nonspecific cellular necrosis. Histopathologic lesions in the liver were mild. PMID- 3348533 TI - Effects of phenobarbital on thiopental pharmacokinetics in greyhounds. AB - The effects of phenobarbital on the pharmacokinetics of thiopental (15 mg/kg IV) were investigated in 12 trained racing Greyhounds. Phenobarbital (16 mg/kg of body weight, PO, q 24 h), administered for 14 days, reduced the area under the curve of plasma concentration of thiopental vs time from 10,688 micrograms.min/ml to 3,224 micrograms.min/ml. Furthermore, the time to recovery from anesthesia (ie, return to standing position) decreased from 103 minutes to 35.7 minutes after phenobarbital. These effects were attributed to an increase in the metabolic clearance of thiopental, as a result of induction of liver enzyme activity by phenobarbital. These results suggested that hepatic metabolism, in addition to distribution, is a factor that must be considered when assessing the difference in drug disappearance rates between Greyhounds and other breeds of dogs. PMID- 3348534 TI - Probenecid infusion in mares: effect on para-aminohippuric acid clearance. AB - Para-aminohippuric acid (PAHA, 0.1 mg/min/kg of body weight) was infused IV into 2 mares, followed by concurrent IV infusion of PAHA and probenecid (0.075, 0.15, 0.25, or 0.35 mg of probenecid/min/kg). Probenecid infusion reduced the clearance of PAHA at serum probenecid concentrations greater than 55 micrograms/ml. At 12 hour intervals, probenecid (in 5 repeated doses - 50, 75, 100, or 200 mg/kg) was administered by gavage to 2 mares. Mean serum probenecid concentration was greater than 55 micrograms/ml for all dosages. At dosages less than 200 mg/kg, accumulation of probenecid in the serum was minimal from the 1st to the 5th dose. At a dosage of 200 mg/kg, probenecid accumulated in the serum from the 1st to the 5th dose. Intragastric administration of 5 doses of probenecid (75 mg/kg) at 12 hour intervals to 6 mares reduced the clearance of PAHA by 50%. Bioavailability of probenecid was 117 and 102% for 2 mares after a single intragastric dose, compared with a single IV dose. PMID- 3348535 TI - Cultivation of Anaplasma marginale from cattle in a Dermacentor cell line. AB - A tick cell line derived from Dermacentor variabilis (RML-15) was inoculated with bovine RBC infected with Anaplasma marginale. Two hours after inoculation, numerous RBC were phagocytized by the tick cells. After one passage of the cell culture, numerous groups of Anaplasma-like particles were seen in the tick cell cytoplasm. Increased numbers of Anaplasma-like particles also were present. Seemingly, Anaplasma can multiply in tick cells. PMID- 3348536 TI - Measurements of bone strain in foals with altered foot balance. AB - Two to 7 days after birth, 9 foals were anesthetized, and strain gauges were applied to lateral and medial aspects of the third metacarpal bone of the left forelimb. In 5 of these foals, strain gauges also were applied to the radius of the left forelimb. Four to 6 days later, foals were walked (5 sets of 10 to 20 strides), and compressive and tensile strains in the bone beneath strain gauges were recorded on paper and diskette. After recording base-line data, a wedge was fitted to the hoof of the limb with the strain gauges, in such a way that the lateral bearing surface was raised, and strains were recorded again. The wedge was left in place, and further recordings were made every 2 to 3 days for 10 days. At the normal walk (base-line data), the compressive strain was higher than the tensile strain in the third metacarpal bone, on the medial side of which the mean principal compressive strain was approximately twice that on the lateral surface. Immediately after application of the wedge, strain values from the medial surface of the third metacarpal bone decreased by 40%, and the lateral surface compressive strain increased by 100%. These changes gradually decreased over 10 days, at which time there was no significant difference from base-line values (P less than 0.05). Similar but much less obvious trends were observed in the radius. Abnormal hoof balance apparently had no lasting effect on compressive forces running through the limb, and the natural situation of higher compressive strain medially was restored quickly. PMID- 3348537 TI - Spinal decompressive procedures and dorsal compartment injuries: comparative biomechanical study in canine cadavers. AB - Effects of decompressive procedures or dorsal injuries on flexion-extension, 4 point bending properties of the L-3 and L-4 motion segment in dogs were quantitated and compared. Hemilaminectomy did not significantly (P less than 0.05) affect mechanical properties of the spine. Bilateral facetectomy caused a small increase in the range of motion and a 56% decrease in ultimate bending strength. Excision of the supraspinous and interspinous ligaments decreased the flexural stiffness of the spine, increased the range of motion of the interspace, and decreased ultimate flexion bending strength 62%. Dorsal laminectomy caused a marked decrease in spine stiffness in all phases of flexion and extension, increased the range of motion, and decreased ultimate flexion bending strength 75%. Seemingly, a hemilaminectomy was preferable to the dorsal laminectomy if adequate decompression and exploration were achieved with the hemilaminectomy. PMID- 3348538 TI - Maternal and fetal toxicity of poison hemlock (Conium maculatum) in sheep. AB - Poison hemlock (Conium maculatum) was toxic to pregnant ewes and their fetuses when fed during gestation days 30 through 60. Maternal effects included trembling, muscular weakness in the neck initially, then progressing to the limbs, ataxia, frequent urination and defecation, and death. Convulsive seizures were not observed. Fetotoxic effects included excessive flexure of the carpal joints with lateral deviation in the front limbs and kinked tails. At term, 7 of 11 lambs had varying degrees of the limb abnormalities, but all lambs appeared clinically normal at 8 weeks after parturition. PMID- 3348540 TI - Race and gender as psychological variables. Social and ethical issues. PMID- 3348539 TI - Ethical and professional dimensions of socially sensitive research. PMID- 3348541 TI - Ethical dilemmas in AIDS research. Individual privacy and public health. PMID- 3348542 TI - Ethical balances in juvenile justice research and practice. PMID- 3348543 TI - Counseling AIDS antibody-positive clients: reactions and treatment. PMID- 3348544 TI - American Lung Association, American Thoracic Society, 1988 annual meeting. May 8 11, 1988, Las Vegas, Nevada. Abstracts. PMID- 3348545 TI - Prevention of stroke during carotid endarterectomy. AB - From 1976 through 1985, 2857 carotid reconstructive procedures were performed on 2087 patients. Postoperative neurologic deficit occurred in 59 patients (2.1%). Thirty one patients (1.2%) suffered deficits that were permanent while 25 patients (0.9%) cleared to be discharged normal. In the last 5 years of the study, an aggressive approach was taken in cases where the patient was noted to have a postoperative neurologic change. It is routine to allow the patient to awaken in the operating room and to perform a simple neurologic examination prior to transport to the recovery room. If a neurologic change occurs during the postoperative period, immediate exploration is undertaken without preliminary testing. With this policy, 20 patients underwent exploration of the operated carotid artery and six of these patients recovered completely. To reduce the stroke rate from carotid endarterectomy (CE), technical errors must be kept to a minimum. Prevention of hypoperfusion with a shunt and careful mobilization of the artery to prevent microembolization should be practiced. Postoperative thrombosis can be decreased by the routine use of platelet antiaggregates and the avoidance of perioperative hypotension. Reperfusion of injury can be minimized by control of postoperative hypertension and proper preoperative selection of patients. Postoperative neurologic deficit following CE remains a relatively rare event and consequently sufficient experience in the treatment of this problem is difficult to acquire. PMID- 3348546 TI - Infected aortobifemoral prosthesis--a dreaded complication. AB - From 1980 to 1985 13 patients were identified with infected aortofemoral grafts. Potential predisposing factors identified included a history of multiple femoral arterial procedures (10 patients; 77%) as well as perioperative infections occurring at the time of a prior femoral operation (five patients; 38%). Patients presented with suppurative groin infections (11) or ruptured pseudoaneurysms (2). Two who had previously undergone bilateral amputations were managed by removal of their aortic grafts without revascularization. Eleven other patients were managed by excision of the entire prosthesis (6 aortic grafts), partial graft excision (five graft limbs) or local treatment alone (three graft limbs). Revascularization through uninfected tissue planes was performed on 14 limbs with salvage of 11 (limb salvage 79%); whereas three limbs not revascularized required major amputation (limb salvage 0%). Despite an aggressive surgical approach five patients (38%) required a major amputation and there were three deaths (23% mortality). Once the diagnosis of an infected graft is made, early graft excision and prompt revascularization are encouraged. PMID- 3348547 TI - Intra-aortic balloon cardiac assist: complication rates for the surgical and percutaneous insertion techniques. AB - A retrospective study was performed to evaluate complications with the two most common intra-aortic balloon pump (IABP) insertion techniques. During a nine year period, 202 patients (51 women, 151 men) underwent IABP cardiac assist utilizing the arteriotomy surgical (103 balloons) and percutaneous (99 balloons) insertion techniques. Complications, including asymptomatic loss of pedal pulse, vascular symptomatic, infection, or balloon rupture occurred in 22.8 per cent of patients. Of the 54 complications, 13 (24%) were asymptomatic loss of pedal pulse, 36 (66.7%) were vascular symptomatic, three (5.5%) were infection, and two (3.7%) were balloon malfunctions. The overall complication rates were 16/103 (15.5%) and 38/99 (38.3%) for the surgical and percutaneous methods, respectively (P = 0.007). Thirty two per cent (33/103) of the patients receiving IABP surgically and 24 per cent (24/99) of those receiving IABP percutaneously died in the hospital (P = 0.34); no death was directly attributable to IABP. The number of patients requiring surgical intervention or removal was not significantly different between the surgical and percutaneous methods (9 versus 18%, P = .06). While the method of IABP insertion did not significantly alter hospital mortality, a significantly greater complication rate was observed with percutaneous insertion (P = .007). This was particularly relevant to complications occurring at the time of removal of IABP. PMID- 3348548 TI - One hundred consecutive carotid endarterectomies without a death or a stroke. AB - One hundred consecutive carotid endarterectomies performed by one surgeon are reviewed. The diagnostic investigations, surgical indications, and operative results are reported. With recent widespread reporting of high complication rates following carotid surgery, particular emphasis was given to this series' low complication rate: no deaths, no strokes, three TIAs. PMID- 3348549 TI - Mesenteric venous thrombosis. AB - Six cases of mesenteric venous thrombosis have occurred in the metropolitan area from 1982 through 1985. The most common findings were nonspecific abdominal pain associated with nausea and vomiting, subjective distress disproportionate to the objective findings, and signs of decreased intravascular fluid volume. In all six cases there was a rapid progression of physical findings to a level commensurate with the initial complaint. The most consistent laboratory abnormalities were an increase in leukocyte precursors, an elevated lactate dehydrogenase, and a mild metabolic acidosis. Mesenteric venous thrombosis is an unusual disease that is difficult to diagnose and manage. PMID- 3348550 TI - Early postoperative femoral-distal bypass graft failure due to vascular clamp injury induced common femoral artery thrombosis. AB - Acute early postoperative femoral-distal bypass graft failure associated with profound lower extremity ischemia is unusual because early graft failure commonly reverts leg circulation to the preoperative status. Two cases are reported where the etiology of profound early postoperative ischemia and graft failure were not due to technical aspects of graft reconstruction itself but rather to vascular clamp injury to a severely atherosclerotic common femoral artery with early postoperative common femoral artery, profunda femoris artery and graft thrombosis. This event requires immediate recognition and common femoral artery reconstruction for limb salvage. PMID- 3348551 TI - Duodenocaval fistula: case report and literature review. AB - Duodenocaval fistulae are rare but may well be the source of gastrointestinal hemorrhage with associated sepsis in patients undergoing surgery and subsequently receiving radiation to the right upper abdomen. Management of these fistulae may be challenging. Diagnosis usually requires a high index of suspicion, particularly in post irradiated patients. PMID- 3348553 TI - Barrett's ulcer. AB - A case of an ulcer developing within previously documented Barrett's epithelium is reported. The patient had symptoms of gastroesophageal reflux for many years and Barrett's esophagus beginning 21 cm from the incisor teeth was documented by endoscopy one year earlier. Hospitalization was necessitated by an upper gastrointestinal bleed which was found to be due to an ulcer at 29 cm from the incisors. There was no inflammation of the surrounding columnar epithelium nor was there any esophagitis within the squamous epithelium. This case documents that ulcers in Barrett's esophagus can arise de novo within the columnar epithelium despite the hypothesis that this epithelium is present because it is more resistant to acid/peptic damage than squamous epithelium. This suggests that some ulcers in Barrett's epithelium may be due to spontaneous degeneration of the epithelium as this patient had no esophagitis, suggesting that gastroesophageal reflux was not causing diffuse damage. PMID- 3348552 TI - Duodenal exclusion for management of lateral duodenal fistulas. AB - The first clinical application of pyloric occlusion with gastrojejunostomy (duodenal exclusion) for management of lateral duodenal fistulas was reported by Berg in 1907. More recently Berne et al. applied this procedure to treat patients with complex pancreaticoduodenal trauma and modified it to include antrectomy with Billroth II reconstruction and tube duodenostomy. Over time the indications for duodenal exclusion have gradually been expanded to include management of actual or anticipated duodenal fistulas arising from operative injury or as a complication of inflammatory or neoplastic diseases. Our recent success using duodenal exclusion and/or diverticularization to manage one patient with duodenal trauma and two patients with nontraumatic forms of duodenal injury resulting in lateral duodenal fistulas caused us to reevaluate the efficacy of this procedure and forms the basis for this report. PMID- 3348554 TI - [Condyloma acuminatum in children]. AB - A retrospective study of eleven children affected of condyloma acuminatum is presented. Authors evaluated: age of presentation and consulting, sex, social history, predisposing factors, characteristic and extension of disease, previous venereal diseases, microscopic pathology, treatment and follow up. Age presentation ranged between 1.5 months and 14 years old. Two were male and nine were female. In two cases obvious sexual abuse was demonstrated; close contact without sexual goals in four; in two transmission during labor existed; early sexual activity in one and they didn't evidence mechanism of transmission in two. Predisposing factors include social problems, lack of hygiene, promiscuity, diabetes, ammoniacal erythema and others. Culture was positive for gonococcus in two children. VDRL test was negative in all cases. All of them were treated with 5% 5-fluorouracil cream. Recovery oscillated between seven and twenty-one days, without adverse reactions, except reddening of adjacent skin. PMID- 3348556 TI - [Familial reciprocal translocations: estimation of the most probable imbalance in the offspring]. AB - Four familial reciprocal translocations detected in a chromosomic study made to a population of newborn babies with two or more congenital defects following the methodology of ECEMC is analyzed. We followed the criteria of pachytene-dyagrem model of Jalbert et al (1980) to predict the most probable mode of imbalance for reciprocal translocations is followed. On the four translocations it was observed the type of segregation which was most probable following that model: three of them produced imbalance by a 3:1 segregation and the other one be adjacent 1. According to these results and regarding that a given translocation produces imbalances almost always by the same mechanism, we can provide a useful information for genetic counselling for these families. PMID- 3348557 TI - [Acute hemoptysis in infants]. PMID- 3348555 TI - [C-reactive protein, lactate and LDH isoenzymes in the cerebrospinal fluid in the diagnosis in childhood meningitis]. AB - C reactive protein lactate and LDH isoenzymes were quantified in CSF of 32 children with meningitis (27 bacterial and 5 viral). Results in cases with bacterial meningitis were as follows. C reactive protein sensitivity was 11.1% and specificity was 100%. Lactate sensitivity was 33.3% and its specificity was 80%. LDH1 and LDH5 had a sensitivity of 44.4%, and specificities of 100 and 60% respectively. Considering these results an has believe that none of these tests is definitive in diagnosis of bacterial meningitis in children. PMID- 3348559 TI - [Congenital giant hiatal hernia. Apropos of 2 cases]. PMID- 3348558 TI - [Neurologic complications of Schoenlein-Henoch syndrome]. PMID- 3348560 TI - [Newborn infants of mothers addicted to heroin. Study of 45 cases]. AB - Authors have studied 45 babies born during past five years to drug-addicted mothers. Increase in number han been remarkable: from 0.095 per thousand live births in 1980 to 1.57 in 1984. There was and 16.3% incidence for preterm infants, 34.8% for low birth weight and 18.6% were small for gestational age. One third (30.2%) suffered infections, mostly sepsis. Morbidity was high in these babies, caused mainly by prematurity. Drug withdrawal syndrome appeared in 26 babies (60.4%) at an age of 13 +/- 10 hours. Fifteen of these babies (57.6%) required pharmacological treatment during 10 +/- 7.3 days, with a good response, and only two cases needed treatment for more than a month. There were no deaths in the neonatal period. In our experience children of heroin addicted mothers form a group difficult to study because their parents give not reliable data, they have high morbidity and true problems begin when they leave hospital. PMID- 3348562 TI - Persistent Campylobacter jejuni infections in patients infected with the human immunodeficiency virus (HIV). AB - We identified Campylobacter jejuni infections in four patients infected with the human immunodeficiency virus (HIV); three had persistent and severe C. jejuni infections. Multiple isolates obtained from each patient had the same biochemical and serotypic characteristics, indicating recurrent infection rather than reinfection with unrelated strains. Serum antibody responses to C. jejuni group antigens by enzyme-linked immunosorbent assay were markedly impaired in the three patients with persistent infection compared with forty-two immunocompetent C. jejuni-infected controls and with the HIV-infected patient who readily cleared the organism. One patient was bacteremic; his blood isolate was killed by normal serum but was resistant to his own serum, whereas a simultaneous stool isolate of a different serotype was sensitive. Failure of two patients to eradicate the organism and long-term administration of erythromycin therapy led to the in-vivo development of resistance to this antibiotic, which is most frequently used to treat C. jejuni infections. PMID- 3348561 TI - High serum cortisol levels in exercise-associated amenorrhea. AB - OBJECTIVE: To determine whether basal cortisol levels are elevated in exercise associated amenorrhea. DESIGN: Survey, with hormone levels measured weekly for 1 month and patients followed clinically for 6 months. SETTING: Volunteers were recruited through media advertisements and fliers. PARTICIPANTS: Ninety-two women were enrolled; 71 (77%) completed the study. Subjects were grouped by menstrual and activity histories reported by a self-administered questionnaire. After 6 months, final groups were assigned: amenorrheic athletes, 19; eumenorrheic athletes, 35; a transition group of amenorrheic athletes who had resumed menses after entering the study, 7; and normal cyclic nonathletes, 10. INTERVENTIONS: Four weekly resting blood samples (0800 to 1000 hours) were obtained and measured for cortisol, estradiol, progesterone, and prolactin levels. Lumbar bone mineral density was measured by dual-photon densitometry. MEASUREMENTS AND MAIN RESULTS: Mean (+/- SE) cortisol levels were higher in amenorrheic athletes (585 +/- 33 nmol/L) than in eumenorrheic athletes (411 +/- 14 nmol/L), transition athletes (378 +/- 33 nmol/L), or nonathletic women (397 +/- 30 nmol/L) (P less than 0.01). Of nine women with abnormally high cortisol levels (greater than 579 nmol/L), eight were amenorrheic athletes, and one was a eumenorrheic athlete. Bone mineral density was lower in amenorrheic athletes than in the other three groups (P less than 0.01). CONCLUSIONS: Increased glucocorticoid levels may be an etiologic factor in exercise-associated amenorrhea. High cortisol levels could also contribute to decreased bone density. The failure of amenorrheic athletes with hypercortisolemia to regain menses within 6 months suggests that they are at risk for a prolonged acyclic state. PMID- 3348564 TI - Muscle and skin infarction after free-basing cocaine (crack). PMID- 3348563 TI - The risk for systemic embolization associated with percutaneous balloon valvuloplasty in adults. A prospective comprehensive evaluation. AB - STUDY OBJECTIVE: To prospectively investigate the evidence for embolic phenomena associated with percutaneous mitral and aortic valvuloplasty. DESIGN: Prospective, consecutive case series before and after balloon valvuloplasty. SETTING: Referral center hospital and cardiac catheterization laboratory. PATIENTS: Consecutive sample of 32 patients having balloon valvuloplasty for critical symptomatic stenosis of the mitral or aortic valve. Twenty-six patients had aortic stenosis; 6 had mitral stenosis. INTERVENTION: Computed tomography of the head, funduscopy, and electrocardiography were done in all patients before and after valvuloplasty. Cardiac isoenzymes were measured serially in 19 patients. MEASUREMENTS AND MAIN RESULTS: Previous cerebral infarction was seen in nine patients, with three showing a new abnormality after aortic valvuloplasty. In one of these patients a funduscopic hemorrhage was detected by photography. Total creatinine kinase and MB fraction were elevated in 1 of 19 patients. Serial electrocardiograms were unchanged in all patients. CONCLUSIONS: The incidence of cerebral neurologic events and myocardial injury are acceptably low after balloon valvuloplasty of calcific aortic and mitral stenosis. Both episodes of symptomatic cerebral infarction occurred in patients with apparent bicuspid aortic valvular stenosis, suggesting that calcific bicuspid aortic stenosis may be associated with more neurologic events after aortic valvuloplasty. PMID- 3348565 TI - Ranitidine-induced granulocytopenia: recurrence with cimetidine administration. PMID- 3348566 TI - Stenotic aortic and mitral valves treated with catheter balloon valvuloplasty in a patient with small valve anuli. PMID- 3348568 TI - A proposal for more informative abstracts of review articles. AB - This proposal presents guidelines for preparing informative abstracts of review articles. Six guidelines are proposed: 1. The abstract should begin with a precise statement of the primary objective of the review. 2. The data sources for the review should be succinctly summarized. 3. The criteria used to select studies from the data sources and the method by which these criteria were applied should be specified. 4. The guidelines used for abstracting data and assessing data quality should be described. 5. The main results of the review and the methods used to obtain these results should be stated. 6. Conclusions and potential applications of the review's results should be clearly and succinctly stated. Application of these guidelines can lead to efficient identification of relevant, scientifically sound review articles, a greater awareness of the vital elements of a good review article, more precise computerized literature searches, and improved peer-review processes. PMID- 3348567 TI - A stool collection device: the first step in occult blood testing. AB - Despite widespread fecal blood testing, the technique of gathering stool for sampling has remained uncontrolled. We sought to describe how patients have contended with this awkward step, to study artifact caused by toilet water, and to construct a collection device that prevents sampling problems. A survey of 250 patients showed that most (56%) had retrieved stools from the toilet basin, 17% used a pan or other household receptacle, 10% used newspaper or tissue paper, and 17% had been unable or unwilling. Sampling stool from the toilet basin introduces error because 4% to 75% of blood leaches from the fecal surface into surrounding water after only 4 to 12 minutes, and many toilet sanitizers cause false-positive guaiac reactions. We describe an inexpensive, disposable stool collector; outpatient compliance has been 97% using this device. To avoid biochemical artifact and facilitate stool sampling, we advocate that a collection device be incorporated into the occult blood testing process. PMID- 3348569 TI - Style notes: eponyms. PMID- 3348570 TI - Clinical competence in acute hemodialysis. Health and Public Policy Committee, American College of Physicians. PMID- 3348572 TI - The patient-doctor relationship. PMID- 3348571 TI - Eponyms. PMID- 3348573 TI - Residency programs in internal medicine. PMID- 3348574 TI - The standard of care. PMID- 3348576 TI - Medical "experts" in litigation. PMID- 3348575 TI - Preventing tampering with prescriptions: the Marton method. PMID- 3348577 TI - Cigarette smoking and the acquired immunodeficiency syndrome. PMID- 3348578 TI - Risks in intrahospital transport. PMID- 3348579 TI - Cytology or biopsy. PMID- 3348581 TI - Methotrexate in rheumatoid arthritis. PMID- 3348580 TI - Cocaine and rhabdomyolysis. PMID- 3348582 TI - Thyroiditis from a seat belt? PMID- 3348583 TI - Urinary retention in diabetic patients. PMID- 3348584 TI - Desmopressin and blood loss. PMID- 3348586 TI - Ibuprofen and antihypertensive drugs. PMID- 3348585 TI - Pleuropneumonia and alkaline phosphatase. PMID- 3348587 TI - Knemometry in childhood: accuracy and standardization of a new technique of lower leg length measurement. AB - Recently, a new anthropometric method of accurate lower leg length measurement (knemometry) was introduced. The present study was performed to investigate rigorously its strengths and weaknesses for auxological purposes, and to promote a standardized method of use. The data are based on 6 x 2200 single estimations of the lower leg length in 90 children of both sexes with normal, tall or short stature aged between 2.4 and 17.1 years. The overall technical error of this measurement was found to be 0.16 mm, which is reduced to 0.13 mm if the first estimation within each series of six is ignored. The following sources of systematic error could be detected: intra-daily variation, dependency on physical pressure put on or removed from the leg, vigorous physical activity prior to the measuring procedure, and a slow but significant correlation between day-to-day variation of lower leg length and body weight (r = 0.299, b = 0.372 mm/kg). There was no covariation with atmospheric parameters such as outside temperature, barometric pressure and others. After elimination of a linear trend from the individual growth curves, there was a remaining day-to-day variation of SD = 0.697 mm. This represents real changes of lower leg length and cannot be explained by the technical error of measurement which contributes to less than 10% of the total variation. Some of this day-to-day variation may be explained by non-linearity of growth. Knemometry appears to be a robust and precise new tool for the investigation of short term kinetics of longitudinal growth. Proposals for a standardized use of this technique are given. PMID- 3348588 TI - Distribution-free estimation of age-related centiles. AB - A method is described for calculating age-related centiles which makes no assumption about the nature of the distribution of the measurement at a fixed age. PMID- 3348589 TI - Marital migration and genetic structure in Kitee, Finland. AB - A genetic analysis of marital migration in Kitee, Finland, is presented. The data are based on 9970 marriages which took place between 1750 and 1877. The results of this analysis are compared with those of previous studies of the population of the Aland Islands, Finland. Analysis of inter-subdivision genetic kinship matrices shows that genetic heterogeneity in Kitee is substantially less than in Aland. This is due primarily to higher rates of migration, both between subdivisions and from outside the population, in Kitee compared to Aland. These differences in migration rates can in turn be attributed to greater geographic isolation in Aland and the contrasting social structures of the two populations. Because of differences in geographic structure and population distribution, geographic distance between subdivisions is a better predictor of inter subdivision genetic kinship in Kitee than in Aland. The Aland Islands are known to have high frequencies of several otherwise rare genetic diseases; in addition, these diseases are distributed very non-randomly among Aland's subdivisions. The genetic structure results presented here suggest that Kitee should have a less unique distribution of genetic diseases. PMID- 3348591 TI - Adiposity indices and clinical opinion. AB - The comparison of various adiposity indices in children and adolescents shows that there is a great similarity between the indices, and also between their ability to distinguish extreme groups. The adiposity indices used are highly correlated with weight and subscapular skinfold thickness, and are not generally independent of height. Differences in these correlations appear during the period of puberty. Discrimination of obese and non-obese subjects by the indices and by clinical opinion agrees in 65%-75% of instances, with no one index agreeing better than the others. PMID- 3348592 TI - Secular shift in menarcheal age of Patiala (India) schoolgirls between 1974 and 1986. AB - The secular shift between 1974 and 1986 in the menarcheal age of Patiala schoolgirls has been explored. A total of 946 girls of higher and lower social classes (type of school being the criterion) were surveyed, out of which 421 were menstruating at the time of investigations. The median ages at menarche (by probits) of higher social class girls were 12.90 +/- 0.64 years in 1974 and 12.54 +/- 0.13 years in 1986, and of lower social class girls 14.40 +/- 0.47 years in 1974 and 13.65 +/- 0.18 years in 1986. The secular shift per decade in higher and lower social class girls is 0.30 years and 0.63 years, respectively. The social class differences during this period in menarcheal age have decreased. PMID- 3348590 TI - Mother-daughter differences in menarcheal age in adolescent girls attending national dance company schools and non-dancers. AB - A combination of genetic and environmental factors is thought to contribute to age of menarche. Adolescent athletes and dancers are much more likely to have a delayed menarche than are non-athletes. To examine the possible differential influence of heredity and environmental factors on menarcheal age, 350 adolescent dancers and non-dancers and their mothers were surveyed. The dancers had a later age of menarche than did the comparison group; their mothers did not differ with respect to menarcheal age, suggesting that delayed menarche in athletes is not solely due to genetic selection as inferred by maternal menarcheal age. Maternal menarcheal age was the best predictor of menarcheal age in the comparison sample, while leanness was in the dance sample. PMID- 3348593 TI - Neurological symptoms and neuropsychological abnormalities in lymphadenopathy syndrome. AB - This case-control study of 39 homosexual or bisexual men who were human immunodeficiency virus (HIV)-seropositive and had lymphadenopathy syndrome and 38 HIV-seronegative homosexual or bisexual men indicates an association between neurological and neuropsychological abnormalities and HIV infection in patients with lymphadenopathy syndrome. PMID- 3348594 TI - Research relative to AIDS. PMID- 3348596 TI - Animal models of AIDS. PMID- 3348595 TI - Virus in the nervous system. PMID- 3348597 TI - Neuropsychiatric consequences of AIDS. AB - As part of a study in progress, neuropsychological tests have been administered to 13 patients with clinical acquired immunodeficiency syndrome, 9 human immunodeficiency virus-seropositive patients, 4 seropositive patients with chronic active hepatitis, 5 seronegative patients with chronic active hepatitis, and 6 healthy controls. Consistent with findings in earlier patient and control groups, the acquired immunodeficiency syndrome patients had substantially lower scores on a variety of cognitive tests. Although the acquired immunodeficiency syndrome group is not education-matched at present, the results are nonetheless consistent with impairments of language function and timed, self-paced performance. Test results obtained may reflect focal and global cognitive impairment as well as motivational decrements in patients with the acquired immunodeficiency syndrome relative to seropositive patients or controls. PMID- 3348598 TI - The AIDS dementia complex: some current questions. AB - The acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) commonly complicates the course of human immunodeficiency virus (HIV) infection and AIDS. Although many of its clinical aspects have recently been brought into clearer focus, and pathogenetic evidence has accrued implicating direct HIV brain infection, there remain a number of fundamental aspects of ADC and HIV nervous system infection that require clarification. These include clearer definition of the clinical syndrome and its variants; development of instrumentation for diagnosis and monitoring the disorder; definition of the epidemiology and natural history of both central nervous system HIV infection and ADC, which may seemingly be discordant; and understanding of both the viral pathogenesis and the biology of resultant brain dysfunction. Elucidation of these fundamental issues will enhance rational development and evaluation of therapy. PMID- 3348599 TI - Cerebrospinal fluid abnormalities in homosexual men with and without neuropsychiatric findings. AB - We have studied cerebrospinal fluid obtained from 38 homosexual or bisexual men participating in a prospective study of the neuropsychological disorders associated with human immunodeficiency virus (HIV) infection. Twenty-two subjects had neuropsychiatric findings and seropositivity, 11 asymptomatic subjects had seroconverted within 6 to 24 months, and 5 subjects were seronegative controls. Only 1 had acquired immunodeficiency syndrome-related complex, and none had the acquired immunodeficiency syndrome when initially studied. There was a high rate of cerebrospinal fluid abnormalities in men with neuropsychiatric findings, including pleocytosis (41%), elevated IgG and IgG index (47%), and oligoclonal bands (18%). Even in the absence of neuropsychiatric findings, the asymptomatic HIV-seropositive subjects frequently had spinal fluid abnormalities. Of those with neuropsychiatric findings, HIV p24 antigen was detectable in cerebrospinal fluid in only 1 individual, yet HIV was isolated in 11 of 16 (69%) compared to 2 of 7 (29%) of those without neuropsychiatric findings. The identification of cerebrospinal fluid abnormalities in individuals known to have become infected within 6 to 24 months supports the hypothesis that the nervous system is an early target for HIV. PMID- 3348600 TI - Preliminary molecular characterization of a human immunodeficiency virus (HIV-I) associated with neuropathology. AB - A human immunodeficiency virus (HIV-I) was isolated from the brain of a patient with progressive dementia but no obvious immunosuppression. This isolate, designated as HIV-IBR, was molecularly cloned and sequenced, and its long terminal repeat (LTR) and envelope sequences were compared with those of other HIV isolates not uniquely associated with dementia. The HIV-IBR LTR showed marked homology with the LTR sequences of the other HIV-I isolates. The predicted amino acid sequence of the external glycoprotein (gp120) of HIV-IBR revealed a pattern of conserved and variable regions similar to that of other HIV isolates. The sequence of the transmembrane portion of envelope, gp 41, was highly homologous to the counterpart region of other isolates. Further analysis is required to determine whether specific sequence variation can account for neurological manifestations of HIV-IBR infection. PMID- 3348602 TI - Immunopathogenesis of human immunodeficiency virus infection in the central nervous system. PMID- 3348601 TI - Role of mononuclear phagocytes and accessory cells in human immunodeficiency virus type I infection of the brain. AB - The cells responsible for persistence of viral infection in the brains of human immunodeficiency virus type I-positive individuals are most likely mononuclear phagocytes. The infection of other cell types within the brain is presumably the result of close interactions with HIV-I-producing cells of the mononuclear phagocytic lineage. During these interactions, both direct effects from HIV-I infection of brain cells as well as indirect mechanisms (namely the response of brain cells to the presence of virus-infected cells, particularly monocytes and macrophages) should be considered. In addition, the genomic variability of HIV-I could play a role in increasing the tropism of the virus for certain cell types. PMID- 3348603 TI - Antimycobacterial activities in vitro and in vivo and pharmacokinetics of dihydromycoplanecin A. AB - The in vitro activity of dihydromycoplanecin A (DHMP A), a new cyclic peptide antibiotic, was compared with those of antimycobacterial drugs such as streptomycin, isoniazid (INH), rifampin, and ofloxacin against several clinically isolated species of mycobacteria, including Mycobacterium tuberculosis, M. intracellulare, and M. kansasii. DHMP A demonstrated stronger activities than other drugs against all species of mycobacteria tested at concentrations of less than 0.0125 to 25 microgram/ml. A marked synergism between DHMP A and INH was demonstrated by the checkerboard technique against M. tuberculosis, M. intracellulare, and M. smegmatis, and the synergistic effect was observed by treatment of the culture of M. smegmatis with DHMP A for at least 3 h prior to treatment with INH. It was also shown that both absorption and excretion of INH in mice were faster than those of DHMP A. On the basis of these results, combination therapy with DHMP A and INH was successfully carried out in experimental tuberculosis in mice infected with M. bovis Ravenel. After a single intravenous administration of 10 mg of DHMP A per kg, its half-life in serum in mice was about 0.5 h and in dogs it was 5.5 h. A single oral administration to dogs of 12.5 mg/kg gave a peak of 5.0 micrograms/ml at 3 h. In these experiments, urinary recoveries within 48 h were 21.0% in mice and 25.2% in dogs. The tissue distribution level of DHMP A in mice after oral administration was in the order of liver greater than kidney greater than serum greater than spleen = lung. The 50% lethal doses of DHMP A for mice were more than 6,000 mg/kg orally and 1,840 mg/kg intraperitoneally. PMID- 3348604 TI - Pharmacokinetics of ribavirin aerosol in mice. AB - The pharmacokinetics of ribavirin administered in single or multiple treatments to mice by small-particle aerosol were monitored in lung, serum, and brain tissues. ribavirin aerosol was administered with a standard drug concentration (20 mg/ml) in the reservoir for 12 h or a high dose (60 mg/ml) for 2 or 4 h. After single or 3-day treatments, ribavirin rapidly accumulated in the lungs at concentrations sufficient to inhibit influenza virus or respiratory syncytial virus (1 to 5 mM). While peak levels of ribavirin in the lungs after the high dose administration were about three times those found with the standard dose, ribavirin was rapidly cleared from the lungs. There was no accumulation of drug in the lungs after multiple treatments. Ribavirin cleared from the lungs was detected in the blood within 15 min. Concentrations in the serum were similar (20 to 30 microM) for standard- and high-dose treatments with either single or multiple treatments. Ribavirin clearance from the serum after treatment was similar for each regimen. Ribavirin also rapidly accumulated in the brain to a similar level (ca. 6 nmol per brain) after standard- or high-dose treatment for 3 days. In contrast to ribavirin in the serum, ribavirin in the brain appeared to be slowly cleared, allowing levels to remain relatively constant during and after treatment. With the interest in viral encephalopathies, further evaluation of the possible advantages of this method of drug administration is warranted. PMID- 3348605 TI - In vitro activities of LY163892, cefaclor, and cefuroxime. AB - The in vitro activity of LY163892, a synthetic oral cephalosporin, was compared with those of cefaclor and cefuroxime against 1,193 clinical isolates. MIC ranges and MICs for 50 and 90% of isolates of the three cephalosporins were comparable. The activities of LY163892 and cefaclor were, however, highly inoculum dependent against beta-lactamase-positive Haemophilus influenzae and Staphylococcus aureus; that of cefuroxime was not. LY163892 and cefuroxime appeared stable in microdilution trays stored at 5 and -20 degrees C for 5 weeks, in contrast to cefaclor which remained stable for more than a week only at -5 degrees C. PMID- 3348606 TI - In vitro evaluation of DuP 105 and DuP 721, two new oxazolidinone antimicrobial agents. AB - DuP 105 and DuP 721 are two members of the oxazolidinones, a new class of synthetic antimicrobial agents with activity against gram-positive bacteria. In vitro tests compared the two new drugs with five other antimicrobial agents against 216 gram-positive isolates representing 4 genera and 10 species. DuP 721 MICs for 50% of the strains tested (MIC50s) ranged from 2.0 to 8.0 micrograms/ml, DuP 105 MIC50S ranged from 4.0 to 16 micrograms/ml, and vancomycin MIC50S ranged from 0.25 to 1.0 microgram/ml. Methicillin-resistant and -susceptible staphylococci were susceptible to ciprofloxacin, vancomycin, and DuP 721. PMID- 3348607 TI - Enterohepatic circulation of NY-198, a new difluorinated quinolone, in rats. AB - Enterohepatic circulation of NY-198 in rats was studied. NY-198 glucuronide in the bile was rapidly hydrolyzed to NY-198 by the intestinal contents. Hydrolyzed and parent NY-198 in the bile were reabsorbed from the intestine. The amount of NY-198 in enterohepatic circulation was 59.8% of that excreted in the bile. PMID- 3348608 TI - Susceptibilities of Hong Kong isolates of multiply resistant Shigella spp. to 25 antimicrobial agents, including ampicillin plus sulbactam and new 4-quinolones. AB - Seventy-two percent of 129 shigella isolates from two Hong Kong hospitals were Shigella flexneri. Twenty-six percent were S. sonnei, and there was only one isolate each of S. dysenteriae and S. boydii. Ninety-six percent of the isolates were resistant to two or more antibiotics, and up to 11 resistances were seen in a single isolate. Fifty-seven percent or more of these isolates were resistant to ampicillin, streptomycin, tetracycline, chloramphenicol, and sulfamethoxazole; and up to twenty-three percent were resistant to kanamycin, trimethoprim, trimethoprim-sulfamethoxazole, and gentamicin. All the isolates were susceptible to amikacin, nalidixic acid, and the newer 4-quinolone agents; and all but one were susceptible to the cephalosporins tested. Only three isolates remained resistant to ampicillin in the presence of sulbactam. Ampicillin plus sulbactam or the newer 4-quinolone agents may be alternatives for the treatment of severe infections caused by multiply resistant shigellas. PMID- 3348610 TI - Penetration of cefpiramide and cefazolin into peritoneal capsular fluid in rabbits. AB - Penetration of cefpiramide and cefazolin into a specific extravascular fluid was measured with rabbits bearing capsules in the peritoneal cavity. A general feature of slow accumulation and elimination of drugs from extravascular sites having low surface area/volume ratios has also been observed in this study. The capsular concentration-time profiles were well expressed by the following equation: C(CF) = A(CF)[e-kel(CF)(t-to)-e-kp(CF)(t-to)], where C(CF), A(CF), kp(CF), kel(CF), and to indicate capsular concentration at time t, constant for the dimension of concentration, capsule penetration rate constant, capsule elimination rate constant, and lag time before penetration occurs, respectively. The kp(CF), kel(CF), and to were 0.139 h-1, 0.059 h-1, and 0.45 h, respectively, for cefpiramide, and 0.448 h-1, 0.0145 h-1, and 0.14 h, respectively, for cefazolin. A(CF) was 22.7 micrograms/ml for cefpiramide and 4.53 micrograms/ml for cefazolin, being parallel to the area under the plasma concentration-time curve for free drug from to to infinity (20.1 micrograms.h/ml for cefpiramide and 3.43 micrograms.h/ml for cefazolin). In conclusion, it is suggested that as well as kp(CF) and kel(CF), the area under the plasma concentration-time curve for free drug from to to infinity may play an important role regarding the circulating reservoir of drugs in determining capsular concentration-time profiles in experimental models for particular extravascular sites of infection, like abscesses into which drugs cannot easily penetrate. PMID- 3348609 TI - A-61827 (A-60969), a new fluoronaphthyridine with activity against both aerobic and anaerobic bacteria. AB - A-61827 (A-60969 is the hydrochloric salt of A-61827) is a new aryl fluoronaphthyridine which is active against aerobic and anaerobic bacteria. The MICs of A-61827 for 90% of strains (MIC90) of staphylococci and streptococci were less than or equal to 1 microgram/ml and were generally 1 to 4 twofold dilutions less than those of ciprofloxacin for these bacteria. The MIC90S of A-61827 for members of the family Enterobacteriaceae and Pseudomonas aeruginosa were also less than or equal to 1 microgram/ml. Ciprofloxacin was 1 to 3 twofold dilutions more active than A-61827 against these gram-negative bacteria. Neisseria gonorrhoeae, Campylobacter jejuni, and Haemophilus influenzae were susceptible to less than 0.06 microgram of A-61827 per ml. The MIC90 of A-61827 for Legionella pneumophila was 0.25 microgram/ml. A-61827 was as potent or 1 to 2 twofold dilutions more potent than ciprofloxacin against these organisms. The MIC90 of A 61827 for all anaerobic bacteria was less than or equal to 4 micrograms/ml compared with less than or equal to 32 micrograms/ml for ciprofloxacin. In mouse protection tests, A-61827 was as active as ciprofloxacin against Escherichia coli, P. aeruginosa, and Salmonella typhimurium and 5 to 10 times more active than ciprofloxacin against Staphylococcus aureus and Streptococcus pyogenes. A 61827 was as active as ciprofloxacin against P. aeruginosa in a mouse pyelonephritis model and more active than ciprofloxacin and metronidazole in a mouse Bacteroides fragilis abscess model. After oral administration of 100 mg/kg to mice, the peak concentrations of A-61827 and ciprofloxacin in serum were 2.3 and 2.4 micrograms/ml and the half-lives in serum were 3.9 and 1.2 h, respectively. PMID- 3348611 TI - Elimination and tissue distribution of the monosaccharide lipid A precursor, lipid X, in mice and sheep. AB - Lipid X (2,3-diacylglucosamine 1-phosphate) is a novel monosaccharide precursor of lipid A (the active moiety of gram-negative endotoxin) and has been found to be protective against endotoxin administered to mice and sheep and against life threatening gram-negative infections in mice. Because of the need to design optimal dosing regimens in experimental models of ovine and murine septicemia, the pharmacokinetic profile of lipid X was investigated in sheep and in two strains of mice by using 32P-labeled lipid X. In sheep, peak whole blood lipid X levels after a bolus injection of 100 micrograms of lipid X per kg were 900 ng/ml. An initial rapid distribution phase of 7.98 +/- 0.1 min was observed, followed by a prolonged elimination phase of 3.0 +/- 0.5 h; the area under the curve from time zero to infinity was 428 +/- 27 ng.h/ml. The serum half-lives of lipid X were slightly shorter than whole blood half-lives, suggesting that lipid X associates with cellular elements. Metabolites of lipid X could not be detected in serum over a 4-h period. Lipid X appears to accumulate mainly in the liver, and the tissue distribution of lipid X resembles that of lipopolysaccharide. The elimination rate of lipid X in mice was approximately four times as rapid as that seen in sheep. Lipid X pharmacokinetics in lipopolysaccharide-sensitive DBA/2J mice were virtually identical with those seen in endotoxin-resistant C3H/HeJ mice. The pharmacokinetics described here should greatly aid in the design and interpretation of animal studies investigating the therapeutic applications of lipid X in gram-negative septicemia. PMID- 3348612 TI - Multiple-dose pharmacokinetics and toleration of intravenously administered cefoperazone and sulbactam when given as single agents or in combination. AB - The multiple-dose pharmacokinetics and toleration of cefoperazone (3 g every 12 h) and sulbactam (1.5 g every 12 h) were studied when these antimicrobial agents were administered continuously over 7 days as a 15-min infusion of individual agents and as a 3/1.5-g cefoperazone-sulbactam combination. Fourteen male volunteers participated in an open, three-way crossover study of Latin Square design with a 1-week washout period between phases. On days 1 and 7 of each phase, serial serum samples and urine were collected for drug assay over a 12-h period. Hematological and clinical chemistry determinations were made within 10 days before the first antibiotic dose and for each treatment phase just before the first dose, on day 4 of treatment, and within 24 h of the last dose. For cefoperazone as a single agent on days 1 and 7, the average maximal concentration in serum (Cmax) was approximately 430 micrograms/ml, the terminal elimination half-life (t1/2) was 1.8 h, and the average percentage of dose excreted unchanged in the urine (%Ur) was 30%. For sulbactam as a single agent, the Cmax was approximately 90 micrograms/ml, the t1/2 was 1 h, and the %Ur was 89% on days 1 and 7. When comparing individual versus simultaneous drug administration, the only pharmacokinetic alteration observed was a statistically significant but minor (about 10%) decrease in sulbactam renal clearance, on both days 1 and 7, resulting in a similar decrease in total body clearance (CL). The area under the curve, apparent volume of distribution by the area method (V), t1/2, and Cmax were not significantly altered. Although cefoperazone pharmacokinetic parameters were not significantly altered when comparing single-agent to combination drug administration, the area under the curve was slightly lower and CL, nonrenal clearance, and V were modestly higher from day 1 to day 7. Because Cmax and t1/2 were unaffected, these minor day effects would not be of clinical significance. Intravenous administration of cefoperazone and sulbactam given as individual agents compared with the combination did not show pharmacokinetic differences that are likely to produce clinically relevant effects. The combination of cefoperazone and sulbactam was well tolerated, and the safety profile of the combination was similar to that either drug given alone under the conditions of this study. PMID- 3348613 TI - Pharmacokinetics and pharmacodynamics of cefoperazone-sulbactam in patients on continuous ambulatory peritoneal dialysis. AB - This study was conducted to determine the pharmacokinetics of the fixed combination antibiotic cefoperazone-sulbactam in patients receiving continuous ambulatory peritoneal dialysis (CAPD). In addition, the pharmacodynamic profile of this combination was determined by the use of mean bactericidal titers against selected bacterial strains. Six noninfected CAPD patients were given a fixed dose of cefoperazone (2 g) and sulbactam (1 g) either intravenously or intraperitoneally over 10 min in a randomized, two-way crossover fashion. The mean peak cefoperazone concentration in serum after intravenous administration was 280.9 micrograms/ml. The mean peak concentration in serum after intraperitoneal cefoperazone administration was 38.9 micrograms/ml and occurred 2 to 4 h postdose. The mean peak sulbactam concentration in serum after intravenous administration was 82.2 micrograms/ml. The mean peak concentration in serum after intraperitoneal sulbactam administration was 24.4 micrograms/ml and occurred at 6 h. The absolute bioavailability of the intraperitoneal dose was 61% for cefoperazone and 70% for sulbactam. Cefoperazone total body and renal clearances were unaffected by renal failure and dialysis. However, both clearance values for sulbactam were reduced markedly. Only intraperitoneal dosing provided peak inhibitory and bactericidal titers in dialysate for all organisms tested. Intravenous dosing provided satisfactory dialysate titers only for very susceptible bacterial strains. End-stage renal disease and CAPD do not alter cefoperazone pharmacokinetics; however, sulbactam dosing may need to be adjusted. PMID- 3348615 TI - Susceptibility of dysgonic fermenter 2 to antimicrobial agents in vitro. AB - Dysgonic fermenter 2 (DF-2) is a fastidious, gram-negative organism well recognized as a cause of fulminant septicemia in patients without spleens or patients with alcoholic cirrhosis. In vitro antibiotic susceptibility testing of eight strains with a Schaedler broth dilution technique revealed DF-2 to be susceptible to all of the antibiotics tested except aztreonam. Previous reports that DF-2 is aminoglycoside resistant were based on disk diffusion or agar dilution assays that may be less reliable given the slow growth of the organism and its requirement for CO2 incubation. Penicillin is commonly used as prophylaxis after dog bites and has excellent activity against DF-2. PMID- 3348616 TI - Nurses need to be taught to write. PMID- 3348614 TI - Impact of ciprofloxacin on theophylline clearance and steady-state concentrations in serum. AB - The effect of a multiple-dose regimen of oral ciprofloxacin (750 mg every 12 h for 11 doses) on the clearance and steady-state concentrations of theophylline in trough (predose) serum was evaluated in nine healthy male subjects, each serving as his own control. Theophylline was taken as a sustained release tablet per os in a dose of 200 mg every 12 h for 19 doses. Theophylline concentrations in serum were measured immediately before each theophylline dose. Ciprofloxacin was administered on study day 4 through the first dose of study day 8. Theophylline concentrations in serum were also measured on study days 3, 6, 8, and 10 at the following times after the first dose of each day: 0, 0.25, 0.50, 1, 2, 4, 6, 8, 10, and 12 h. Steady-state theophylline concentrations in trough serum were significantly higher during ciprofloxacin treatment (day 8) than before (day 3) or after (day 10) ciprofloxacin administration (P less than 0.01). Likewise, theophylline clearance was significantly slower (P less than 0.01) during ciprofloxacin treatment (day 8) than before it (day 3) or after it (day 10). The magnitude of ciprofloxacin-induced changes was approximately 30%. These results suggest that a multidose regimen of ciprofloxacin significantly slows the clearance of theophylline and elevates theophylline concentrations in serum. PMID- 3348617 TI - Hazards of laser plume questioned. PMID- 3348618 TI - Job satisfaction and personality. Are they related? PMID- 3348619 TI - Autologous salvage of blood. Perioperative nursing considerations. PMID- 3348620 TI - Planning and documentation. Addressing patient needs in a day surgery setting. AB - Day surgery has reduced the time allowed for patient contact, but it has not reduced the need for assessment, planning, and delivery of patient care. Day surgery, however, has shifted some responsibility from nurses to patients and their families. Our goals in developing a preoperative assessment plan were to ensure consistent and thorough patient assessment; enhance problem identification and guide appropriate interventions; provide evaluations based on the needs of the day surgery patient; assist patients and families in assuming increased responsibility for postoperative care; provide achievable and manageable documentation of patient information gathered in a compressed amount of time; and facilitate communication between the patient and the health care team. We feel our assessment documenting system meets these goals and allows nurses and patients to adapt to the changes in traditional roles both parties experience when day surgery procedures are performed. PMID- 3348621 TI - Vaginal eversion repair. Sacrospinous ligament fixation procedure. PMID- 3348622 TI - Care of instruments, scopes, and powered surgical instruments. PMID- 3348623 TI - Aseptic barrier materials for surgical gowns and drapes. PMID- 3348624 TI - Working in a stressful environment does not supersede the right to be free from verbal or physical abuse. PMID- 3348625 TI - Preoperative assessments: can we afford to do without them? PMID- 3348626 TI - Characteristics of a successful ambulatory surgery program. PMID- 3348627 TI - A faster way to reconstitute dantrolene sodium for malignant hyperthermia. PMID- 3348628 TI - [Therapy of advanced neuroblastoma by the protocol of the Welfare Ministry used by the Sawaguchi Group]. AB - Five patients with advanced neuroblastoma were treated with the protocol of the Welfare Ministry used by the Sawaguchi group. This protocol consists of cyclophosphamide (CPM), vincristine (VCR), 4'-O-tetrahydropyranyladriamycin (THP ADM) and cisplatinum (CDDP). Two patients treated with this protocol as the first therapy obtained partial remission. Two patients who had obtained complete remission before the treatment with this protocol remained in complete remission after the treatment. One patient who had shown poor response to the therapy given before treatment with this protocol also showed poor response to the protocol. The most significant side effect with this protocol was myelosuppression, the severity of which was closely related to the dose of THP-ADM. Damage to the liver, kidney and heart was not very significant. We advocate that patients with advanced neuroblastoma can obtain complete remission with the aid of surgery and radiotherapy, etc., if they are treated with the present protocol as the first therapy. PMID- 3348629 TI - [Study on the chemosensitivity of liver cell carcinoma by subrenal capsule assay]. AB - Chemosensitivity of liver cell carcinoma was studied by subrenal capsule assay. The method of assay was based on Bogden's one, but the antitumor activity was evaluated by tumor growth inhibition rate (TG-IR). The anticancer agent with more than 50% TG-IR was judged as positive in the chemosensitivity test. Of 3 human hepatoma cell lines transplanted in the subcutaneous space of nude mice, all of 3 were evaluable. The positive rates of ADR, MMC, CDDP, 5-FU and CPA were 66.7%, 100%, 66.7%, 100% and 0%, respectively. Of 24 patients who provided fresh tumor specimens for the assay, 12 (50%) were evaluable. The positive rates of ADR, MMC, CDDP, 5-FU and CPA were 25%, 16.7%, 16.7%, 33.3% and 8.3%, respectively. Our study suggested that 5-FU, MMC and ADR were comparatively active against the hepatoma cell, CDDP was less active than these 3 agents, CPA was inactive. These results seem to justify the use of current anticancer agents against hepatic cell carcinoma and indicate the usefulness of SRC assay for selecting chemotherapeutic agents against liver cell carcinoma. PMID- 3348630 TI - [Inhibition of pulmonary metastases in mice by beta-cyclodextrin-benzaldehyde]. AB - The effect of beta-cyclodextrin-benzaldehyde (CDBA) on the pulmonary metastasis in C3H/He mice was examined. When mice were treated daily with CDBA, 3 weeks later the number of lung nodules developed after i.v. inoculation of 1 X 10(6) RCT (+) cells was significantly decreased. The mean numbers of the lung nodules were 69.9 and 73.4 in the water-and cyclodextrin (CD)-treated mice, respectively. However, these were 17.8, 9.8 and 2.9 in 0.5, 5 and 25 mg/mouse per day CDBA treated mice, respectively. And also, daily treatment of CDBA prolonged the survival time of the tumor bearing mice in both experimental and spontaneous metastasis studies. Two or three weeks after subcutaneous inoculation of RCT (+) cells (1 X 10(6) cells) to the foot pad, left hindlimbs were amputated and then mice were daily treated or untreated with CDBA. Five weeks after tumor inoculation, the number of lung nodules was counted. Twenty eight point six and 100% of untreated mice had lung metastases when amputation was carried out 2 (earlier operation group) and 3 (latero peration group) weeks after tumor inoculation. However, in CDBA-treated mice, these values were noticeably decreased, that is, 6.7% and 60% in earlier and later operation groups, respectively. Furthermore, in the later operation group, mean number of the lung nodules in CDBA-treated mice was only 2.7 while this was 12.9 in untreated mice. These data suggest that CDBA improve the survival time of tumor bearing mice through the inhibition of the lung metastasis. PMID- 3348631 TI - [Effect of immunosuppressants on the subrenal capsule (SRC) assay as a chemosensitivity test]. AB - Six-day SRC assay as a chemosensitivity test has an advantage of high predictive rate for clinical response. However, it is pointed out that very few viable tumor cells are observed at the end of the assay, so that it may make the assay results unreliable. In this paper, we tested the effect of immunosuppressants on SRC assay using Walker carcinosarcoma originated from Wistar rat xenografted under the renal capsule of BDF1 mice. The changes of tumor size, pathological features and proliferative ability of xenografted tumor under the renal capsule of mice treated with cyclophosphamide, mizolibine or cyclosporin A are examined. Only cyclosporin A treatment could maintain the viable tumor cells and proliferative ability of the tumor grafted under the renal capsule 21 days after transplantation. In order to compare the original 6-day SRC assay developed by Bogden et al, we applied immunosuppressants to the 6-day assay. It is suggested that cyclosporin A and mizolibine amplify the sensitivity of tumor in 6-day SRC assay. PMID- 3348632 TI - [Cryopreservation of circulating stem cells in large quantities]. AB - We have collected peripheral blood mononuclear cells in large quantities by leukapheresis from children with malignant disorders. The cells were fractionated on discontinuous gradients of Percoll for enrichment of hematopoietic stem cells and reduction of sample volume. They were subsequently frozen in a programmed freezer and stored in liquid nitrogen. This procedure allows a reduced DMSO volume to be infused into patients and increases storage space. The recovery rates of progenitors evaluated by freeze-thaw analysis in small aliquots were 89% for granulocyte-macrophage colony-forming units (CFU-GM) and 106% for granulocyte, erythroid, macrophage, megakaryocyte colony-forming units (CFU GEMM). Hence, we conclude that circulating stem cells can be collected and cryopreserved in large quantities without any loss of capacity. Further studies to evaluate the relevance of performing rescue surgery with these stem cells following marrow-ablative chemotherapy are underway. PMID- 3348633 TI - [Combined use of lentinan with X-ray therapy in an experimental mouse tumor system (Part 2). Combined effect on the MM102 syngeneic tumor]. AB - C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation. PMID- 3348634 TI - [Combined use of lentinan with X-ray therapy in an experimental mouse tumor system (Part 3). Combined effect on metastatic tumors]. AB - Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF1 mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamous cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmonary metastasis system of Lewis lung carcinoma, a marked suppression of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free. PMID- 3348635 TI - [An experimental study on SRCA (subrenal capsule assay)--comparison of the test between normal and nude mice]. AB - Six-day SRCA using normal mice developed by Bogden et al. is a promising in vivo chemosensitivity test. However, this method has a problem on the influence of the host reaction. We compared the tumor growth kinetics and host reaction between normal and nude mice. The tumor diameter increased until day 6 in normal and day 16 in nude mice, but the histological finding revealed many host reactive cells and few viable tumour cells on day 6 in normal mice, and well preserved tumour cells on day 16 in nude mice. These results were supported by flow cytometrical analysis. Autoradiogram using 3H-TdR showed a recovery of labeling index to the steady label by day 1. This index was similar between normal and nude mice. When antitumor activity of adriamycin, cisplatin or mitomycin C was compared with nude mice system, the order of effectiveness was the same as the system using nude mice implanted tumor cells subcutaneously and given the drugs intraperitoneally, but different in normal mice. PMID- 3348636 TI - [Experimental study of the 6-day subrenal capsule assay by cyclophosphamide pretreatment]. AB - For the purpose to suppress the host immune reaction in subrenal capsule assay (SRCA) using normal immunocompetent mice, the effects of cyclophosphamide (CPM) pre-treatment (CPM 180 mg/kg day-1 s.c.) were compared with cyclosporine A (CSA) treatment (CSA 60 mg/kg s.c. daily). CPM and CSA suppressed host reaction until day 6 and day 12, respectively. However, in the histological evaluation of day 6 tumor, there was no difference between two groups. Mouse serum levels of CPM were measured by a bioassay as indicated by the cytotoxicity against P388 cells, to evaluate its residual activity against implanted tumor. No cytotoxicity was observed in the serum of 36 hr. after CPM injection. The antitumor activities of several chemotherapeutic agents against serially transplanted human esophageal cancer xenograft (IMEs-1) in untreated control group and CPM pre-treated group of SRCA were compared with the subcutaneous transplantation assay in nude mice. In all agents, the drug activities in CPM pre-treated group were similar to that in nude mice assay system. The increase of toxicity in CPM pre-treated group was very light. The immunosuppressive activity of CPM were also tested in 14 clinical samples. CPM suppressed the host reaction satisfactorily in all samples. These results suggest the usefulness of CPM pretreatment for suppressing the host reaction in SRCA. PMID- 3348637 TI - [A clinical trial to prevent the renal toxicity of cisplatin by administration of bismuth subnitrate]. PMID- 3348638 TI - Concern over safety of SAGM blood. PMID- 3348639 TI - Peptic ulceration: long term outcome. PMID- 3348640 TI - Hearing loss due to mumps. PMID- 3348641 TI - Non-convulsive status epilepticus. PMID- 3348642 TI - Topical iodine, breastfeeding, and neonatal hypothyroidism. PMID- 3348643 TI - Sudden and unexpected death between 1 and 5 years. PMID- 3348644 TI - Lower limb deformity and prevention of scoliosis in cerebral palsy. PMID- 3348646 TI - Child psychiatry and the undergraduate. PMID- 3348645 TI - Clinical risk factors and periventricular leucomalacia. AB - Two hundred infants of below 1501 g at birth were regularly examined with real time ultrasound using a 7.5 MHz transducer. Abnormalities were categorized as periventricular haemorrhage (PVH) (n = 107) or periventricular leucomalacia (PVL), with or without PVH (n = 52). Of the group with PVL, 25 had the appearances of prolonged flare without cavitation. Prospective assessments of up to 50 potential clinical risk factors were made wherever possible on each infant including stratification of all blood gas and systolic blood pressure data. Multivariate logistic regression analyses confirmed a strong correlation between immaturity and PVH but this was not found in cases of PVL. Independent variables associated with PVL included pneumothorax, maximum bilirubin concentration, surgery, and the proportion of time the infant's PaCO2 remained above 7 kPa. There was a very strong inverse correlation between anaemia and PVL. Systolic blood pressure data were carefully analysed and there was no relation between either hypotension or antepartum haemorrhage and the development of PVL. PMID- 3348647 TI - Paediatric intensive care in a district general hospital. AB - Five years' experience of paediatric intensive care in a district general hospital were analysed retrospectively. A total of 54 infants and children required respiratory support during this time--21 on a high dependency area of the children's ward and 33 on a general intensive care unit. Forty two (78%) of the patients survived, and 33 (61%) of the patients required respiratory support within four hours of admission, thus the experience of the local paediatric and anaesthetic team was crucial to the management of these children. Good intensive care for children can be provided within a district general hospital. PMID- 3348649 TI - Long term follow up of patients with early onset anorexia nervosa. AB - A long term follow up (mean 7.2 years) of 30 children with anorexia nervosa (mean age at onset 11.7 years) was carried out. The outcome was good in only 18 (60%), 10 children remaining moderately to severely impaired and two died. Poor prognostic factors included early age at onset (less than 11 years), depression during the illness, disturbed family life and one parent families, and those in which one or both parents had been married before. PMID- 3348648 TI - Factors associated with maternal choice to provide breast milk for low birthweight infants. AB - Factors associated with maternal choice to provide milk for premature infants were investigated in 925 mother/infant pairs in five hospitals. A well educated, married, primiparous mother aged 20 or over who delivered a baby boy by caesarean section was nearly 1000 times more likely to choose to express her milk than a mother who was poorly educated, single, multiparous, and aged under 20, delivering a female infant vaginally. Evidence from the five centres suggested that hospital staff have little influence on a mother's choice of feeding method. The major differences between the populations of babies whose mothers do or do not choose to provide milk, raise important issues concerning the interpretation of data from non-randomised clinical trials of feeding premature infants. PMID- 3348651 TI - Training programme for senior registrars in community paediatrics. AB - Consultant paediatricians with a special interest in community child health are being appointed in many parts of the United Kingdom but there are few training posts or programmes for this specialty. A training programme for senior registrars in the northern region that three doctors have completed and in which six doctors are currently engaged is presented. PMID- 3348650 TI - Insulin dependent diabetes in thalassaemia. AB - Diabetes mellitus was observed in 29 of 448 patients with thalassaemia major attending seven Italian centres. Twelve patients, at onset of clinical diabetes, presented with an asymptomatic glycosuria, 13 with ketosis, and four with ketoacidosis. All were diagnosed after 1979, at a mean age of 17 years. Mean age at diagnosis of diabetes was lower in patients born in the last two decades. In these patients transfusions were started at a younger age and pre-transfusion haemoglobin concentration, serum ferritin concentration, incidence of liver disease, and the presence of a family history of diabetes were higher than in patients born previously. Although 27 (93%) cases had iron chelating treatment the mean serum ferritin concentration was 5600 micrograms/l; 25 (92%) of these patients had signs of liver impairment. The determination of C peptide in 10 patients showed a wide variation in pancreatic beta cell function, and insulin requirements ranged between 0.15 and 1.72 U/kg body weight. Metabolic control was generally poor. The onset of diabetes mellitus was followed in most patients by the appearance of other endocrine or cardiac complications, or both. Fourteen patients died within three years of presenting with overt diabetes. Haemosiderosis, liver infections, and genetic factors seemed to be crucial in diabetes development. Thalassaemic patients developing clinical diabetes mellitus are at high risk for other complications and should be strictly monitored, especially for thyroid impairment. PMID- 3348652 TI - Spastic hemiparesis and presumed prenatal embolisation. AB - An infant with clinical evidence of prenatal right subclavian arterial occlusion subsequently developed left hemiparesis with cystic infarction of the territory of the right middle cerebral artery. Perinatal strokes have not been reported with signs of limb ischaemia at birth; this finding may be a warning of possible simultaneous cerebral infarction. PMID- 3348654 TI - Pledgets in ingrowing toenails. AB - Eighty children had cotton wool pledgets inserted under the nail corner for ingrowing toenails. Success was achieved in 44 (72%) of the 61 children followed up for a mean of 2.5 years. Appearance was excellent and compliance high. Initial insertion under anaesthesia improved the results, and chronicity did not adversely affect the outcome. PMID- 3348653 TI - Aerosol treatment abuse. AB - A 4 year old boy with excellent inhaler technique was found to be abusing his salbutamol and beclomethasone dipropionate inhalers. This resulted in aggressive behaviour and probable hallucinations. PMID- 3348656 TI - Blood counts in extremely low birthweight infants. AB - White blood, neutrophil, and platelet counts were higher in 101 infants with appropriate weight for gestational age than in 42 infants who were small for gestational age. The recognised postnatal rise in counts was seen in the infants of appropriate weight, but in the infants who were small for gestational age the counts fell for the first three days. PMID- 3348655 TI - Acrodermatitis chronica atrophicans. AB - Two cases of acrodermatitis chronica atrophicans associated with Borrelia burgdorferi infection are reported; to our knowledge these are the first cases reported in children. PMID- 3348657 TI - Maternal narcotic abuse and the newborn. AB - In 50 infants born to women who continued to take heroin during all or part of their pregnancy the drug withdrawal symptoms were mild and were noted in 21 infants (42%). Only nine infants required treatment. Sudden infant death syndrome occurred in two infants at 4 and 6 months. PMID- 3348658 TI - Effect of supine posture on peak expiratory flow rates in asthma. AB - In order to determine the effect of supine posture alone on the peak expiratory flow rate (PEFR) in children with asthma, 22 children with asthma of varying severity had PEFR readings taken in the standing position and subsequently at 30 minute intervals in the supine position for a period of up to four hours. In order to minimise any stress factors no other procedures--for example, taking of blood specimens--were performed during the duration of the tests, which were carried out in a relatively dust free room with no curtains and minimal furniture. Fifteen non-asthmatic children acted as controls. The results showed a significant drop in the PEFR readings in the supine position in asthmatic children compared with the controls; this reverted back to baseline levels on assuming an upright posture at the end of the test without any medication. It is concluded that airflow obstruction can be induced by supine posture per se in asthmatic children; this may be a major factor contributing to nocturnal wheeze or cough. PMID- 3348659 TI - Adolescent growth and pubertal progression in the Silver-Russell syndrome. AB - The pattern of growth and development of 18 adolescent children with the Silver Russell syndrome was studied. Mature height was about -3.6 standard deviation scores in both sexes. This is comparable to the height reduction at diagnosis, which has been reported previously. The pattern of puberty and adolescent growth was essentially normal and occurred at a marginally earlier time than normal, although in this small series the differences were not significant. In the girls there was a tendency to gain subcutaneous fat after puberty. This trend was not apparent in the boys. PMID- 3348660 TI - Histology of breast development in early life. AB - Histological examination of the breasts of 26 infants and young children who died suddenly between the ages of 3 weeks and 2 years was performed. The glands were composed of well formed lobules surrounded by dense interlobular stroma, while within the lobules there was looser connective tissue. The lobules contained ducts, many of which were dilated and contained secretions. Foci of extramedullary haematopoiesis were found, and in the older infants, fat was prominent within the connective tissue of the breast. Myoepithelial cells were regularly present. No sex differences in breast development at this time were noted. Newborn breast development did not regress rapidly after birth and secretory activity continued for many months in both sexes. This study shows that the human mammary gland remains active for many months after birth and may continue to grow and secrete. The findings are not consistent with the current view that breast development in infancy results from stimulation from 'pregnancy hormones.' It is more likely that the infant's own gonadal secretions are responsible. PMID- 3348662 TI - Diagnosis of functional illness presenting with gait disorder. AB - Nine children presented with disturbances of gait that were not caused by organic disease. They all fulfilled at least four out of eight diagnostic criteria. Diagnosis in all had been delayed while organic causes were excluded. Unnecessary and sometimes potentially harmful procedures were performed or proposed for each child. Identification of such children earlier may avoid morbidity and facilitate management. PMID- 3348661 TI - Lipoprotein lipase, hepatic lipase, and carnitine in premature infants. AB - Twenty six preterm infants were studied at the age of 2, 7, and 26 days. The activities of lipoprotein and hepatic lipase in plasma taken 15 minutes after a heparin bolus of 100 IU/kg had been given and the concentrations of carnitine in serum and urine were measured. The mean gestational age was 31 weeks (range 26-35 weeks) and birth weight 1580 g (range 840-2280 g). Thirteen infants weighed under 1500 g at birth (very low birth weight), 20 were of appropriate weight for gestational age and six were small for gestational age. Lipoprotein lipase activity was higher in the preterm infants of appropriate weight than in the infants of very low birth weight and those who were small for gestational age. At the age of 2 or 7 days the activity of lipoprotein lipase in the preterm infants (mean (SEM) 46.2 (4.3) mumol free fatty acid/ml/hour) was, however, higher than in term infants and adults. Multivariate regression analyses showed that weight and relative birth weight together explained 58% of the variance of lipoprotein lipase activity but only 3% of the variance of hepatic lipase activity. Serum carnitine concentration was lower in the preterm infants than in term infants. Urinary excretion of carnitine increased progressively with age but was independent of serum concentration and carnitine intake. Urinary excretion of total carnitine was significantly greater in the infants who were small for gestational age (mean (SEM) 754 (203) nmol/mg of creatinine, n = 6) than in the infants of appropriate weight (161 (22.0) nmol/mg of creatinine, n = 12) but acyl/free carnitine ratio was smaller in the infants who were small for gestational age than in infants of appropriate weight (0.56 v 5.5). The results indicate that the slow elimination of fat from the circulation in preterm infants less mature than 32 weeks of gestation can hardly be explained by low lipoprotein lipase activity. PMID- 3348663 TI - Joint mobility and motor development. AB - The association of joint hypermobility and motor development was sequentially investigated in 715 infants from the ages of 8 to 14 months. Seven joints were evaluated for mobility, and each infant underwent a physical and neurological examination. Parents were given a Denver Developmental Parents' Questionnaire. All subjects with a general developmental delay, systemic illness or syndrome were excluded. The infants were classified as having normal or delayed motor development with normal or delayed joint mobility. They were re-examined six months later. Multivariate statistical techniques was used for categorical analysis, and three joints were found to be significantly associated with motor delay at the first examination--hip abduction, elbow hyperextension, and foot dorsiflexion. Of the 715 infants, 126 had joint hypermobility and of these 38 (30.2%) had motor delay. Sixty four of 589 (10.9%) with normal joints had delayed motor development. Six months later 23 out of 35 of the group with joint hypermobility and 42 out of 53 of the group with normal joints had normal motor function. Joint hypermobility is associated with an increased incidence of motor delay in infancy. Over the ensuing six months most of the subjects will catch up. These findings, indicating a favourable prognosis, have implications regarding clinical assessment and parental counselling. PMID- 3348664 TI - Increasing medical burden of child abuse. AB - During the decade January 1976 to December 1985, as a result of increased public awareness, the numbers of reported (but not proved) cases of abuse to children living in South Birmingham increased thirty-fold; the incidence of detected and proved cases of abuse increased fourfold. The increase was principally due to bruises, scalds, and neglect. The numbers of serious fractures and brain injuries did not increase. The first case of sexual abuse was reported in 1981 and this was followed by a subsequent rise in the detection rate. The combination of increased reporting, increased incidence of proved abuse, and the necessity for increased supervision of families and intervention has created a serious burden on the child health services that may necessitate a reduction in services to other children. Alternative ways of tackling the problems of child abuse may have to be introduced, but they may have unwelcome consequences. PMID- 3348665 TI - Cleft palate and glue ear. AB - The invariable presence of otitis media with effusion in children with cleft palate aged from 2 to 20 months is confirmed in a prospective trial, and the diagnosis was made in each case by myringotomy. Treatment planning should take account of this, and long term ventilation of at least one ear seems to be mandatory in order to correct bilateral congenital deafness. Close cooperation between otologist and plastic surgeon is essential for diagnosis and treatment of otitis media in these patients. PMID- 3348666 TI - Evaluation of infants by echo planar imaging after repair of diaphragmatic hernia. AB - Three infants were studied by echo planar imaging after repair of congenital diaphragmatic hernias. Total lung volume and individual lung volumes were estimated using echo planar imaging. In the two patients with left sided hernias, the right lung was more than twice as large as the left. The patient with a right sided hernia had developed emphysema on the right side, and the right lung was twice as large as the left when estimated by echo planar imaging. Echo planar imaging studies took less than five minutes to perform and no sedation was required. PMID- 3348667 TI - Diphtheria--the continuing hazard. AB - An unimmunized schoolchild with no history of foreign travel developed severe diphtheria. Epidemiological investigations led to the discovery of a child in the same class with cutaneous diphtheria who had just returned from Bangladesh; this highlights the importance of swabbing all skin lesions acquired in endemic areas during any outbreak investigation. PMID- 3348669 TI - Cognitive development in transposition of the great vessels. AB - Ten children who had had transposition of the great vessels (TGV) repaired, deep hypothermia, and cardiac arrest were examined. Seven children with acyanotic heart disease and 12 unaffected siblings were tested for comparison. Their intelligence, academic achievement, and behaviour was studied. The group with TGV had lower performance subscores on the intelligence test, an increase in somatic complaints, and aggressive behaviour. PMID- 3348670 TI - When is meconium stained liquor actually bile stained vomit? AB - Three babies said to have had 'meconium stained liquor' were subsequently found never to have passed meconium. The green discoloured liquor was the result of bilious vomiting in utero secondary to intestinal obstruction. PMID- 3348671 TI - Mercury concentration in cord blood. AB - The mean mercury concentration measured in cord blood from 51 inner city babies born at Guy's Hospital was significantly higher (37 nmol/l v 20 nmol/l) than that from 17 babies born at the Royal Devon and Exeter Hospital, which serves a more rural population. PMID- 3348668 TI - Neonatal screening for cystic fibrosis. AB - Two groups of patients with cystic fibrosis were compared. The screened group, detected with an improved neonatal screening assay for immunoreactive trypsin, developed fewer chest infections requiring treatment and gained more weight than the unscreened group. Early diagnosis by screening seems to affect early morbidity. PMID- 3348674 TI - Human retroviruses and paediatric disease. PMID- 3348673 TI - Conductive education for motor disorders: new hope or false hope? PMID- 3348672 TI - Acrocyanosis due to imipramine. AB - An 11 year old girl who was being treated for enuresis with imipramine developed acrocyanosis of the hands and feet. All biochemical and haematological investigations gave normal results. When imipramine was stopped the girl recovered within three days. PMID- 3348675 TI - Aetiology of growth hormone deficiency. PMID- 3348676 TI - Psychological adjustment and diabetic control. PMID- 3348677 TI - Dexamethasone in bronchopulmonary dysplasia. PMID- 3348678 TI - Giving drugs per rectum for systemic effect. PMID- 3348679 TI - The disability of short stature. PMID- 3348680 TI - Glycosylated haemoglobin in cystic fibrosis. PMID- 3348681 TI - Rotavirus encephalitis. PMID- 3348682 TI - Selective examinations on starting school. PMID- 3348684 TI - A 'new' manoeuvre for removing foreign bodies from the nose. PMID- 3348683 TI - Enuresis in children. PMID- 3348685 TI - Recidivist clients: a review of pilot data. PMID- 3348686 TI - The relationship of nurses' caring behaviors with hopefulness and health care outcomes in adolescents. PMID- 3348687 TI - A comparative study of primary and team nursing models in the psychiatric care setting. PMID- 3348688 TI - Between diagnosis and death: the case for studying grief before death. PMID- 3348689 TI - The hospitalized AIDS patient and the psychiatric liaison nurse. PMID- 3348690 TI - Coping with psoriasis and its psychosocial consequences. PMID- 3348691 TI - Male-to-female transsexualism: a case for holistic nursing. PMID- 3348692 TI - Early primary correction of tetralogy of Fallot. PMID- 3348693 TI - Which way in?--The thoracotomy incision. PMID- 3348694 TI - Early primary repair of tetralogy of Fallot. AB - Young age, low weight, and the requirement for transannular patch reconstruction of the right ventricular outflow tract (RVOT) are thought to adversely affect intracardiac repair of tetralogy of Fallot. Forty patients underwent complete repair between January, 1984, and January, 1987. Only infants with pulmonary atresia, complete atrioventricular canal, or coronary artery anomalies were shunted initially. The malalignment ventricular septal defect was closed with a Dacron patch. Infundibular resection was minimized. All atrial communications were left open. Thirty-four patients (85%) had a transannular RVOT patch, and 2 patients (5%) had a nontransannular patch. All 10 infants weighing 3.4 to 9.6 kg had a transannular RVOT patch at 7 weeks to 12 months of age. An RVOT patch was used in 26 of 30 children operated on between 1 and 6 years of age (median age, 24 months). No patient undergoing intracardiac repair died. Postoperative RVOT pullback gradients were between 0 and 35 mm Hg (mean, 18.5 mm Hg). Postoperative pulmonary artery saturation (mean, 73%) did not reveal any residual ventricular septal defect. The right ventricular/arterial pressure ratio was always less than 0.6 (mean, 0.4). All children are doing well at follow-up from two to 37 months. Serial echocardiograms reveal no residual ventricular septal defect and only 1 moderate RVOT gradient. Follow-up cardiac catheterization in 15 patients revealed no residual ventricular septal defect and RVOT gradients between 5 and 35 mm Hg. The right ventricular/left ventricular pressure ratio was always less than 0.6 (mean, 0.48). The early and late results justify continued primary repair of tetralogy of Fallot in symptomatic children, regardless of age or weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348695 TI - An improved technique to facilitate transcervical thymectomy for myasthenia gravis. AB - We have used the transcervical method of thymectomy in patients with myasthenia gravis and believe that complete thymectomy is accomplished with minimum morbidity. For the past eight years we have used an improved technique for the transcervical approach, employing a specially designed sternal retractor that permits improved visualization of the anterior mediastinum. We have reviewed 65 patients operated on between 1977 and 1986. Patients were assessed using a modified Osserman classification (0 = asymptomatic; 1 = ocular signs and symptoms; 2 = mild generalized weakness; 3 = moderate generalized weakness; 4 = severe generalized weakness, respiratory dysfunction, or both). The mean grade for all patients at the time of thymectomy was 2.7. At most recent follow-up, the mean clinical grade was 0.5. In addition, 85% of patients were free of generalized weakness, 95% had improved by at least one grade, and 86% had improved by two or more grades. Comparing these results with those reported following thymectomy through a sternotomy reveals that the transcervical approach gives equivalent results. PMID- 3348696 TI - Aortic valve replacement with the Starr-Edwards prosthesis: a comparison of the first and second decades of follow-up. AB - There are few prostheses in current use that allow 20-year follow-up. This report compares the rates of valve-related complications during the first and second decades following aortic valve replacement with the Silastic ball prosthesis. (table; see text) Valve-related complication rates with this prosthesis have been low overall. Performance characteristics of this valve have remained stable through the second decade of follow-up. These results should be used as the standard in the evaluation of long-term results with other more recently introduced mechanical and tissue valves. PMID- 3348697 TI - Survival and "event-free" analysis of 785 patients with Bjork-Shiley spherical disc valves at 10 to 16 years. AB - Seven hundred eighty-five patients underwent Bjork-Shiley spherical-disc valve replacement from 1970 to 1976. There were 268 mitral valve replacements (MVR), 227 aortic valve replacements (AVR), 65 double-valve replacements, and 225 "combined" procedures. A 97.2% follow-up (mean, 12 years) was achieved. With an operative mortality of 4.1% for MVR, 8.4% for AVR, 15.4% for double-valve replacement, and 12.4% for combined procedures, the 12-year survival was most closely related to age at valve replacement: age less than 50 years, 70%; age 50 through 59 years, 52%; and age 60 years or more, 38%. Twenty-four patients (3.1%) (6 who had MVR, 5 who had AVR, 1 who had double-valve replacement, and 12 who had combined procedures) had a thrombosed valve 1 to 134 months postoperatively; this is equal to 0.36 thrombosed valve per 100 patient-years. One hundred eighteen embolic episodes occurred in 94 (13%) of the operative survivors or 1.8 emboli per 100 patient-years. There were major bleeding complications in 0.5% of patients and minor bleeding complications, in 4.0%. Endocarditis appeared in 30 patients (4.2%) or 0.4 episode per 100 patient-years and paravalvular leaks, in 20 patients (2.8%). The event-free survival by age group and valve site at 5, 10, and 12 years is presented. Events included death, thrombosed valves, strokes, bleeding, emboli, paravalvular leaks, and endocarditis. There were 5.3 events per 100 patient-years excluding operative deaths. PMID- 3348698 TI - Pulmonary homograft implantation for ventricular outflow tract reconstruction: early phase results. AB - The pulmonary valve homograft (PH) has been reported to have potential advantages over the aortic valve homograft, including a larger diameter, a thinner wall, and decreased intrinsic calcification. From January 16, 1986, to July 14, 1987, eight consecutive patients underwent repair of congenital cardiac anomalies using a cryopreserved PH. Patients ranged in age from 18 months to 32 years. Diagnoses included tetralogy of Fallot with pulmonary atresia (3 patients); tetralogy with absent pulmonary valve (1 patient); corrected transposition with pulmonic stenosis (1 patient); transposition of the great arteries, ventricular septal defect, and pulmonic stenosis (2 patients); and double-outlet right ventricle with pulmonic stenosis (1 patient). The PH was implanted orthotopically in the patient with absent pulmonary valve, and in the other 7 it was placed as a valved extracardiac conduit. Two of the tetralogy patients with severe bifurcational pulmonary stenosis and another with nonconfluent pulmonary arteries and origin of the left pulmonary artery from a patent ductus arteriosus had their repairs facilitated using the branching pulmonary arterial portion of the PH. There were no hospital or posthospital deaths. Postrepair right ventricular to left ventricular systolic pressure ratios were a mean of 0.35 at 18 hours postoperatively (range, 0.21-0.61). All patients were studied with Doppler and echocardiography after repair. The mean gradient across the PH was 9 mm Hg (range, 2-27 mm Hg), and no pulmonary valve incompetence was present. One patient (12.5%) required reoperation seven months after repair for conduit revision due to compression by the sternum and is now well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348699 TI - Transthoracic exposure for anterior spinal surgery. AB - The anterior approach to the vertebral column is used to treat fractures, spinal deformities, and destructive lesions secondary to tumor or infection. The thoracic surgeon, working with orthopedic surgeons and neurosurgeons, is uniquely qualified to provide surgical exposure expediently and assist in postoperative care. Forty-five patients with spinal deformities secondary to trauma (18 patients), congenital anomalies (16 patients), neoplastic disease (7 patients), and inflammation (4 patients) were treated by a transthoracic (37 patients) or thoracoabdominal (10 patients) anterior approach to the vertebral column. Two patients had subsequent operations. Free and vascularized rib grafts were used for stabilization and fusion with good results and few complications (8 patients). These results indicate that interspecialty cooperation results in expedient surgical exposure and good postoperative care. PMID- 3348700 TI - Marfan's syndrome: combined composite valve graft replacement of the aortic root and transaortic mitral valve replacement. AB - Echocardiographic studies in patients with Marfan's syndrome indicate that 95% eventually have aortic root dilatation, mitral valve prolapse, or a combination of these. Both lesions can progress and require operation for aortic root aneurysm, aortic valve insufficiency, and mitral valve insufficiency. This report reviews the simplified treatment of 6 patients by combined composite valve graft replacement of the aortic root and transaortic mitral valve replacement at one operation. All patients survived and are well for periods extending from 1 month to 12 months. PMID- 3348701 TI - Reflux patterns in patients with achalasia without operation. AB - Five patients with achalasia who had not had an operation underwent esophageal manometry and 24-hour, ambulatory pH monitoring to determine the pattern and extent of esophageal reflux. One patient had reflux within normal limits. In 2 patients, reflux occurred 0.5% of the total time and no episodes of supine reflux were recorded. In the 2 remaining patients, reflux was measured 16.8% and 55.3% of the total time; however, in both patients, these results were influenced by lengthy bouts of supine reflux. These indices of reflux were not influenced by differences in resting lower esophageal sphincter tone, position, or length. Twenty-four-hour esophageal pH monitoring can be useful in the preoperative assessment of patients with achalasia, and the information obtained might influence the choice of operative procedure. PMID- 3348702 TI - Temperature dependency of calcium-induced reperfusion injury in the isolated rat heart. AB - The temperature dependence of Ca-induced reperfusion injury was studied in an isolated rat heart preparation. Hearts were subjected to 90 minutes of hypothermic arrest (20 degrees C) followed by 15 minutes of reperfusion at 20, 28, or 37 degrees C with a reperfusate containing various concentrations of Ca (0.1-2.55 mM). When reperfusion was started at 37 degrees C, the Ca concentration in the reperfusate significantly affected both postischemic functional recovery and creatine kinase leakage. Bell-shaped dose-response curves were observed. The optimal Ca concentration for 37 degrees C reperfusion was between 0.3 and 0.7 mM. When reperfusion was started at 20 degrees C, neither functional recovery nor creatine kinase leakage was dependent on the Ca concentration in the reperfusate. At 28 degrees C, functional recovery was not dependent on the Ca concentration, however, creatine kinase leakage was. These results indicate that Ca-induced reperfusion injury depends on the temperature of the reperfusate and that the boundary temperature of the reperfusate at which Ca-induced reperfusion injury becomes manifest seems to be near 28 degrees C. PMID- 3348703 TI - Effect of electrophysiological testing on ejection fraction during cardioverter/defibrillator implantation. AB - To evaluate the effect of repeated induction of ventricular tachycardia or ventricular fibrillation, or both, in patients with poor left ventricular function, we performed intraoperative two-dimensional echocardiography in 6 patients undergoing implantation of the automatic implantable cardioverter/defibrillator. Changes in left ventricular ejection fraction in sinus rhythm were assessed before the first inducible ventricular arrhythmia and after a mean of 6 +/- 1.9 (SD) episodes of ventricular tachycardia or ventricular fibrillation. During the procedure no significant change in mean ejection fraction was observed (28 +/- 14 versus 27 +/- 17%). Only 1 of the 6 patients studied had a change in ejection fraction greater than 3% (a decrease from 20 to 11%). In an overall clinical series of 38 primary implants or generator changes (including electrophysiological testing) in 29 patients, 1 patient recovered after postoperative inotropic support and 1 died of acute postoperative ischemic heart failure. We conclude that ventricular arrhythmias induced during automatic implantable cardioverter/defibrillator implantation have no immediate deleterious effects on ejection fraction in most patients with compromised left ventricular function and without ongoing ischemia. PMID- 3348705 TI - An unusually intractable Schatzki ring. AB - Most patients with Schatzki's ring have dysphagia that can be relieved by esophageal dilation. We report an unusual case in which dysphagia caused by a Schatzki ring could not be managed conservatively. The obstructing ring was excised through a gastrotomy approached by a left-sided thoracotomy. An antireflux procedure was done after elimination of the ring. Five years later, the patient remained symptom free. PMID- 3348704 TI - Myocardial protection with blood cardioplegia in ischemically injured hearts: reduction of reoxygenation injury with allopurinol. AB - Myocellular injury mediated by oxygen radicals potentially limits myocardial protection in ischemically damaged hearts. This damage may be greater with oxygen carrying blood cardioplegic solutions. A major mechanism of oxygen radical production is the conversion of hypoxanthine to uric acid by xanthine oxidase. In 16 anesthetized dogs, we studied whether adding allopurinol, a xanthine oxidase inhibitor, to blood cardioplegia would improve recovery of left ventricular (LV) performance and oxygen consumption. Millar transducer-tipped catheters and minor axis ultrasonic crystals were placed to assess LV performance by the slope of the end-systolic pressure-minor axis diameter relationships (Emax). Following total vented bypass, the hearts underwent 30 minutes of normothermic ischemia and then hypothermic blood cardioplegia with 1 mM allopurinol (N = 8) or without allopurinol (N = 8). Postischemic LV performance was significantly better with allopurinol than without (49.5 +/- 8.0 versus 17.4 +/- 4.1% of preischemic Emax; p less than 0.004). Postischemic LV oxygen consumption in the beating working state, calculated from LV blood flow (15 microm microspheres) and oxygen extraction, was comparable to preischemic values with and without allopurinol (10.2 +/- 1.2 versus 8.6 +/- 1.2 ml O2/100 gm/min). We conclude that allopurinol enhancement of blood cardioplegia increases myocardial protection in severely ischemic ventricles. PMID- 3348706 TI - Double-outlet left atrium with intact ventricular septum. AB - The clinical course and surgical repair of double-outlet left atrium with intact ventricular septum in a 13-year-old girl are presented. The only outlet of the right atrium was a secundum atrial septal defect, and the left atrium drained into both ventricles through two atrioventricular valves. To our knowledge, there has been only one other published report of repair of double-outlet left atrium. PMID- 3348707 TI - Embolectomy for acute pulmonary artery occlusion following Fontan procedure. AB - A 5-year-old child experienced acute hemodynamic decompensation and hypoxia four weeks following an uneventful Fontan procedure for univentricular heart. Cardiac catheterization revealed complete occlusion of the left pulmonary artery, and emergent pulmonary artery embolectomy was performed. The source of the embolus was the atrial septal patch. Because of the altered hemodynamics following the Fontan procedure, stasis of right atrial blood and thrombus formation may occur. Routine anticoagulation immediately following operation is recommended. Prompt diagnosis and treatment with embolectomy may be lifesaving. PMID- 3348708 TI - Muscle-sparing posterolateral thoracotomy. AB - We have developed a technique for posterolateral thoracotomy that allows adequate exposure for most thoracic operations, yet spares both the latissimus dorsi and serratus anterior muscles. Postoperative pain is decreased, functional recovery is improved, and patients can frequently be discharged earlier from the hospital. Although the time for opening is slightly prolonged, closing time is less and the incision can easily be converted to the standard muscle-splitting approach if more room is required. PMID- 3348709 TI - Locating previously "stripped" venous systems and harvesting of lesser saphenous vein. PMID- 3348710 TI - Atrial septal defect for right ventricular failure. PMID- 3348711 TI - Surgical treatment of aortic aneurysms. PMID- 3348712 TI - Late complications of colon interposition. PMID- 3348713 TI - Information sources that influence physiatrists' adoption of new clinical practices. AB - As part of a mail survey of physiatrists' views of conducting research, respondents were queried regarding information sources that influenced their introducing a clinical innovation into their practices in the past two years. Complete information was obtained from 356 individuals. The reported practice innovations were categorized as follows: (a) evoked potentials (6% of respondents); (b) electrophysiologic diagnostic procedures other than evoked potentials (19%); (c) other diagnostic/assessment procedures (11%); (d) transcutaneous nerve stimulation (6%); (e) physical treatment procedures other than transcutaneous nerve stimulation (22%); (f) medication (5%); (g) psychologic or social intervention (4%); and (h) altered methods of service delivery (27%). Considered across all practice innovation categories, the average relative importance (in descending order) of the information sources was as follows: (1) discovery in the individual's own practice; (2) a meeting, lecture, or continuing education course; (3) a clinical coworker; (4) a write-up in the clinical literature; (5) the individual's own research; (6) a patient; (7) a write-up in the research literature; (8) a textbook; and (9) the representative of a drug firm or equipment manufacturer. Additional findings concern variables which distinguished a group of 43 individuals who reported introducing no innovation into their practices for the preceding two years, compared to the 356 individuals who did so. PMID- 3348714 TI - Multiplicity in rehabilitation research: a quantitative assessment. AB - Recent studies indicate that rehabilitation researchers frequently include multiple tests of significance in their investigations. This study examined the possibility that the Type I error rate in rehabilitation research is inflated due to the inappropriate analysis of data from multiple significance tests. The incidence of Type I error was computed for a sample of rehabilitation research. The results revealed a Type I error assumed level of 5% (p less than .05). The argument is made that methods to determine the rate of Type I error should be routinely used in rehabilitation research. PMID- 3348715 TI - The art of medicine: subjective measures as predictors of outcome in stroke and traumatic brain injury. AB - This study was designed to explore new ways of predicting the functional outcomes of stroke and brain injury patients. Upon admission and initial assessment of functional performance, we used an on-line computer program to indicate the most important and subjective judgment items to set rehabilitation goals for patients. The functional performance and discharge outcomes of patients from an inpatient program were measured by using five nonmedical functional items from the patient evaluation conference system (PECS). For stroke patients we most frequently selected motor loss, perceptual/cognitive deficit, spasticity, sensory deficit (PECS medical items), and comprehension (subjective cue). For traumatic brain injury patients, however, we selected motor loss, perceptual/cognitive deficit, spasticity (PECS medical items), communication, and comprehension (subjective cues). Data were statistically analyzed using the Fisher Exact Test. Of the medical function items, a level of independence in the sensory deficit function in stroke patients at admission was associated with a patient achieving independence in ambulation at discharge. Demonstrating a moderate or maximum level of attention, concentration, and realism was positively related to a patient achieving a level of independence in ambulation at discharge. Independence in the function items of behavior and interaction was associated with moderate or maximum levels of comprehension at admission. In traumatic brain injury patients, none of the subjective cues were associated with achieving independence at discharge in any of the functional levels. This paper demonstrates the value of developing a way to assess subjective measures that are based on their ability to predict outcomes. Using such a method, new predictive measures can be developed. PMID- 3348716 TI - Occult proximal deep vein thrombosis: its prevalence among patients admitted to a rehabilitation hospital. AB - This study was designed first to determine the prevalence of occult proximal deep vein thrombosis (DVT) in stroke patients admitted to rehabilitation hospital using the technique of impedance plethysmography (IPG), and second, to identify clinical findings which may be indicators of an increased risk for the development of proximal DVT. Impedance plethysmography was performed on 105 consecutive stroke patients within one week of admission to our hospital. It was found that 34 out of 100 patients with adequate studies had abnormal IPG, two out of the 34 had known DVT, leaving 32 out of 98 with undiagnosed DVT (19 on the paretic side alone, nine bilateral, and four on the nonparetic side). Using logistic regression analysis, it was determined that profound weakness, male gender, interval between the stroke and IPG, edema, and leg hyperpigmentation were independently associated with positive IPG. Since IPG has a high positive predictive value for proximal DVT, one must assume that most of our patients with positive IPG have proximal DVT. Routine screening of stroke patients for DVT seems indicated and probably should include noninvasive venous studies such as serial IPG. The most efficient screening protocol needs to be determined. PMID- 3348717 TI - Electric impedance measurements in quadriplegia. AB - Previous experimental studies have shown that measurements of electric impedance of the whole human body relate to body fluid volumes. Measurements using two properly selected current frequencies have been purported to be useful in determining the sizes of extracellular and total body fluids. In this study, measurements of whole body impedance were performed on 20 healthy able-bodied subjects and 20 patients with quadriplegia at the frequencies of 1.5kHz and 150kHz. Differences found between the two groups suggest that the ratio of interstitial body fluids to total body fluids in quadriplegic patients is higher than in healthy subjects. This finding is consistent with previous body composition studies conducted on quadriplegic patients using a radioisotope technique, which have suggested a relative increase of extracellular space. PMID- 3348718 TI - Professional ice hockey players: physiologic, anthropometric, and musculoskeletal characteristics. AB - Twenty-seven players from a National Hockey League (NHL) team were evaluated for maximal aerobic power, body composition, and muscle strength and flexibility upon reporting to training camp. Aerobic power was determined with a maximal treadmill exercise test. Body composition was determined by underwater weighing. Muscle strength of the internal and external shoulder rotator muscles and the knee flexors and extensors were determined isokinetically at 30 degrees/sec. Strength of the hip adductors was determined isometrically. The average (+/- standard error) maximal oxygen consumption (VO2max) for all players was 53.4 +/- 0.8 ml x kg-1 x min-1. When players were grouped by their usual playing positions (Goalies = G, n = 4; Forwards = F, n = 15; and Defensemen = D, n = 8) there were no differences in VO2 max, resting or maximal heart rate, and exercise test duration. Although G (77.7 +/- 3.2 kg) were significantly lighter than D (88.5 +/ 1.9 kg) and F (86.1 +/- 1.9 kg), there were no significant differences between player positions in height or percentage of body fat (9.2 +/- 0.9%). Measures of absolute muscle strength and muscle strength adjusted for body weight were similar for G, F, and D. Goalies, however, had significantly more flexibility in the hip and groin musculature than F and D. Although team averages for muscle strength and flexibility were normal and symmetric, ten players (37%) exhibited significant musculoskeletal strength and flexibility deficits. PMID- 3348719 TI - Clonidine effect on spasticity: a clinical trial. AB - Clonidine was used as an adjunct to baclofen in 55 patients with spasticity due to spinal cord injury. Dosage was held at the minimum effect amount for those who responded. No effect was seen in 24 patients (44%), although 31 (56%) benefitted from the drug. Patients were grouped as quadriplegics or paraplegics, having complete or incomplete lesions. Of all quadriplegics, seven of 11 complete (64%) and 17 of 25 incomplete patients (68%) responded; among the paraplegics, six of 15 complete (40%) and one of four incomplete patients (25%) improved. Side effects were limited to postural hypotension necessitating reduction in dosage in three patients that were successfully treated; in the unsuccessfully treated group, one patient had insomnia, one had dizziness, and one had drowsiness. PMID- 3348721 TI - Cardiopulmonary functioning in adolescent patients with mild idiopathic scoliosis. AB - This study measured the physical work capacity of adolescent subjects with idiopathic scoliosis to determine whether cardiopulmonary restrictions begin to occur in the early stages of the condition. Nineteen adolescents (four males, 15 females) between the ages of 10 and 17 years (means = 13.4), with idiopathic thoracic scoliosis, served as subjects. The mean scoliotic curve was 21.5 degrees. Each subject had his/her height, weight, and percent body fat (Lange caliper) recorded. Resting vital capacity and forced expiratory volume were evaluated using standardized clinical spirometry techniques. Work capacity was measured via a continuous graded incremental exercise tolerance test, using a treadmill. A running protocol was used. Heart rate was continuously monitored by an ECG, and a Beckman Metabolic Cart analyzed ventilation (VE), breathing rate (f), and oxygen uptake (VO2) every minute. Twelve of the subjects had vital capacity measures that were one or more standard deviations below normal and also had VO2max scores below 40ml/kg/min. Subjects with curves of 25 degrees or higher had a mean VO2max of 32.6ml/kg/min, while subjects with curves of less than 25 degrees had a mean VO2max of 42.6ml/kg/min. It appears that some pulmonary limitations begin even in mild curves. Curves greater than 25 degrees also appear to affect work capacity. PMID- 3348720 TI - Motor assessment scale for stroke patients: concurrent validity and interrater reliability. AB - This study was conducted to establish the concurrent validity and interrater reliability of the Motor Assessment Scale (MAS) for stroke patients. Thirty hemiplegic subjects were tested with the MAS and the Fugl-Meyer Assessment (FMA), a reliable and validated test of motor function in stroke patients. The high correlations obtained between the total scores on the MAS and the FMA (r = .88) and between specific item scores (except sitting balance) (r = .28 to .92) provide support for the concurrent validity of the MAS. Interrater reliability coefficients for the total MAS score and individual items on the MAS (except tone) were also high and significant. PMID- 3348722 TI - Treatment of adult lower extremity lymphedema with the Wright linear pump: statistical analysis of a clinical trial. AB - Seventy-three adult lymphedema patients with 78 affected lower extremities were treated with the Wright Linear Pump. All patients were admitted for a 48-hour clinical trial. Comparison of circumferential limb measurements before and after a 48-hour treatment period using a repeated measures analysis of variance showed statistically significant improvement (p less than 0.00005). Although the improvement appeared to be somewhat more pronounced for men than for women, both sexes experienced an important reduction in leg circumference after therapy. Other factors such as age, etiology, previous use of the Jobst pump, or duration of lymphedema did not appear to influence the extent of improvement. These data clearly indicate that the Wright Linear Pump is an effective treatment for lower extremity lymphedema in adults. PMID- 3348723 TI - Speech prosthesis retention problems in dysarthria: case report. AB - Prosthesis retention and adaptation problems in the management of dysarthria due to paralysis of the palatopharyngeal mechanism has been frequently reported in the literature. This report describes treatment of speech prosthesis retention difficulty in a 20-year-old woman who sustained a cranial cerebral trauma in a motor vehicle accident. Residual deficits included moderate-to-severe dysarthria with a significant palatopharyngeal valving disorder, higher level cognitive impairments, and long-term memory deficits. Speech intelligibility was maximized via the fitting of an intraoral speech prosthesis. Sensory perceptual changes created by the appliance resulted in prosthesis retention problems. When traditional desensitization techniques were unsuccessful, introduction of a topical anesthetic, Zylocaine Viscous, blocked the sensory feedback loop and eliminated the retention problem. PMID- 3348724 TI - Scuba diving: taking the wheelchair out of wheelchair sports. AB - In the past, physicians prohibited patients with neuromuscular disease or disability from participating in scuba diving. This report highlights the opportunities that self-contained underwater breathing apparatus (scuba) affords to physically handicapped individuals, to move without assistive devices in a gravity-free environment. The experience of a person with T10 paraplegia is used to illustrate the applicability of a new system of evaluation, training, and certification for scuba diving to patients with a wide variety of disabilities, such as paraplegia, quadriplegia, amputation, cerebral palsy, and poliomyelitis. This review also discusses equipment needs, potential risks, and safety precautions. Physicians are encouraged to support those handicapped individuals who choose to explore the submerged two thirds of our planet for its recreational as well as its potential vocational opportunities. PMID- 3348725 TI - Traumatic spinal cord injury complicated by AIDS related complex. AB - It is estimated that one to two million people in the US have antibodies to the human T-lymphotropic virus Type III/lymphadenopathy-associated virus (HTLV III/LAV) and are consequently at risk for developing acquired immunodeficiency syndrome (AIDS). As the number of carriers of this infection increases, so does the expected incidence of this population for acquiring disabilities that require rehabilitative services. We report a traumatic spinal cord injured patient with resultant quadriplegia who has HTLV-III/LAV infection. Presented are the difficulties in classifying the manifestations of the HTLV-III/LAV infection in such a patient. Many of the symptoms of AIDS may be attributed to complications of recently acquired quadriplegia. This is added to the psychologic and social strains on a patient who has already lost permanent function due to quadriplegia. Implementation of educational programs to meet staff, family, and patient needs regarding their concerns and questions significantly reduced anxiety on the rehabilitation unit. Because the possible life expectancy can still be quite long, AIDS patients warrant rehabilitation programs. This necessitates that health care professionals in rehabilitation become familiar with AIDS, as they are likely to be involved in the care of patients with AIDS in the future. PMID- 3348727 TI - Tissue compliance meter. PMID- 3348726 TI - Paraparesis in a patient with Crohn disease resulting from septic arthritis of the hip and psoas abscess. AB - A psoas abscess is a recognized complication of Crohn disease. Less commonly, septic arthritis has been described with this entity. The occurrence of both these complications together in Crohn disease is quite rare. A 56-year-old patient with Crohn disease presented with weakness and pain in both lower extremities. Computerized body tomograms demonstrated a large psoas abscess with fistulous connections to the bowel as well as extending into the capsule of the left hip joint. X-ray examination revealed evidence of acute septic arthritis. Electromyographic studies demonstrated lumbosacral plexus involvement bilaterally. The patient subsequently underwent ileocolectomy with drainage of the left psoas abscess, followed by extensive inpatient rehabilitation. Some immediate strength improvement was noted bilaterally. At discharge, the patient remained paraparetic. In patients with known history of Crohn disease, a psoas abscess should be considered when there are symptoms of lower extremity pain, hip flexion contractures, and progressive weakness. PMID- 3348728 TI - Self-directed medical knowledge program. Study guide and pretest. Rehabilitation in joint and connective tissue diseases. Rehabilitation of musculoskeletal and soft tissue disorders. PMID- 3348729 TI - Acute cholecystitis in the diabetic. A case-control study of outcome. AB - The influence of diabetes on the risks associated with the operative treatment of acute cholecystitis has not been clearly defined. Therefore, a case-control study of 72 diabetics requiring urgent operation for acute cholecystitis was undertaken. Patients were matched for age, gender, and date of surgery with nondiabetic controls. Review of patient records revealed no significant difference in hospital stay or severity of operative and pathologic findings. However, diabetics suffered significantly more morbidity (38.9%) than nondiabetics (20.8%). Moreover, diabetic infection-related complications occurred at a rate nearly three times that of controls (19.4% vs 6.9%). The only mortalities were experienced by diabetics (4.2%) and were the direct result of the effects of sepsis. These findings suggest that acute cholecystitis in diabetics is associated with a higher incidence of infection-related complications and supports the need for expeditious operative therapy in symptomatic patients. PMID- 3348731 TI - The role of preoperative radionuclide left ventricular ejection fraction for risk assessment in carotid surgery. AB - Radionuclide ejection fraction (EF) and ventricular wall motion were determined in 73 patients before 82 carotid operations (79 carotid endarterectomies [CEAs] and three cervical carotid-subclavian bypasses). The EF was 55% +/- 13%, ranging from 21% to 77%. Thirty-three percent (24/73) had low EF (less than or equal to 50%), and 44% (28/63) had myocardial wall motion abnormalities. Perioperative cardiac complications, including myocardial infarction (MI), new ventricular arrhythmia, or severe congestive heart failure, were present after 12.2% (10/82) of the operations. Perioperative MI was present in 4.9% (4/82); in 50% of these it was fatal. Perioperative (30-day) stroke was present in 2.5% (2/79) of those undergoing CEA. Life table analysis revealed overall survival was lower in patients with EF of 35% or less vs those with EF over 35% during follow-up (522 +/- 280 days). Perioperative cardiac complications were more frequent with EF of 35% or less, occurring in 43% (3/7) vs 9% (7/75) of cases with EF over 35%. There was no statistical difference in perioperative mortality, but cumulative mortality differed, being 57% (4/7) in those with EF of 35% or less vs 11% (7/66) in patients with EF over 35%. Patients with EF of 35% or less are at increased risk for perioperative cardiac complications and reduced overall survival following carotid surgery. PMID- 3348730 TI - Femur fracture with associated soft-tissue injury produces hepatic ischemia. Possible cause of hepatic dysfunction. AB - Clinical studies demonstrate that early debridement and operative fixation of femur fractures in multiply injured patients lowers both the incidence and severity of hepatic failure. Perhaps the single most important determinant of hepatic function is nutrient hepatic perfusion. This study compares systemic and hepatic blood flow in rats that have sustained femur fractures with or without associated soft-tissue injury. Femur fracture without soft-tissue trauma resulted in a hyperdynamic state with normal blood flow distribution at 24 hours after injury and normal hemodynamics at 48 hours. When femur fracture was associated with soft-tissue trauma, the elevated cardiac output at 24 hours was not matched by a proportionately elevated hepatic blood flow. In this latter group, the cardiac output was normal at 48 hours, but the hepatic perfusion defect remained. Retained fracture fragments, hematoma, and injured and necrotic soft tissue may serve as a stimulus leading to a pathologic reduction in hepatic perfusion. PMID- 3348732 TI - Effects of sodium hypochlorite (Dakin's solution) on cells of the wound module. AB - This study investigates the effects of sodium hypochlorite, or Dakin's solution (DS), on the function and viability of cells of the wound module (neutrophils, fibroblasts, and endothelial cells). For functional studies, the influence of DS on the in vitro migration of neutrophils was evaluated. Our data indicate that DS (2.5 x 10(-2)% to 2.5 x 10(-4)%) results in greater than 90% inhibition of the migration of both stimulated and nonstimulated neutrophils. Electron microscopy and trypan blue evaluation of neutrophils exposed to DS at these concentrations revealed normal structural features, which indicates that the observed reduction in neutrophil migration is not a result of cell death. In contrast to neutrophils, cultured fibroblasts and endothelial cells exposed to DS (2.5 x 10( 2)% or 2.5 x 10(-3)%) for 30 minutes show marked cell injury characterized by convoluted nuclei, cytoplasmic vacuolization, dilated endoplasmic reticulum, and swollen mitochondria on electron microscopy. These data suggest that DS, even at very dilute concentrations, is toxic to cells of the wound module. We therefore recommend abandonment of the use of DS in open wounds. PMID- 3348733 TI - Temporal relationship of hepatocellular dysfunction and ischemia in sepsis. AB - To determine whether hepatic dysfunction in sepsis results from hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent either cecal ligation and puncture or sham operation. After either two or six hours, effective hepatic blood flow was measured using the galactose clearance method. Hepatocytes were isolated and intracellular sodium and potassium and glucose production were measured. Hepatic blood flow in septic rats decreased as early as two hours after sepsis when compared with sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight). Intracellular sodium and potassium levels and glucose production in septic rats were not significantly different when compared with controls at two hours. After six hours, hepatic blood flow remained depressed and intracellular sodium level was increased compared with sham-operated rats (41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9 mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs 111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose production was decreased in septic rats after six hours when compared with controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data suggest that hepatic blood flow is decreased before alterations in intracellular sodium and potassium as well as glucose production. PMID- 3348734 TI - Prevention of contraction of patched intestinal defects. AB - Neomucosal growth on a serosal patch might increase intestinal surface area in the short-bowel syndrome but is limited by contraction of the patched defect. Our aim was to reduce contraction by mechanical or pharmacologic means. Ileal defects (2 x 5 cm) were patched with colon serosa in 14 rabbits. Group 1 (n = 5) had a plastic splint sutured to the defect edge. Group 2 (n = 4) received hydrocortisone acetate and vitamin A. Group 3 (n = 5) was the control group. Four weeks after patching there was significantly less contraction in groups 1 and 2 compared with group 3 (72.3% +/- 5.6% and 50.0% +/- 5.8% vs 31.9% +/- 1.8% initial defect size). Epithelial coverage of the defect was greater in groups 1 and 3 than in group 2. Disaccharidase activity of neomucosa and surrounding mucosa was significantly decreased in the steroid-treated rabbits. Contraction of a serosal patch can be reduced by mechanical and pharmacologic measures that may enhance the clinical applicability of this technique. PMID- 3348736 TI - Comparison of survival in cardiac surgery at a Veterans Administration hospital and its affiliated university hospital. AB - Survival data were reviewed for 3330 open cardiac procedures from 1975 through 1984 at the William S. Middleton Memorial Veterans Hospital, Madison, Wis, and the University of Wisconsin Hospitals and Clinics, Madison. Respective operative survivals were 98.6% and 98.7% for myocardial revascularizations with vein graft or internal mammary artery (CABG), 96.2% and 96.8% for CABG reoperation, 97.8% and 95.9% for aortic valve replacement, 96.3% and 90.3% for aortic valve replacement plus CABG, 100.0% and 94.9% for mitral valve replacement, and 100.0% and 82.9% for mitral valve replacement plus CABG. There were no significant differences in six-year survival curves between hospitals despite threefold differences in average annual caseload (88 vs 294). This suggest that residency directed cardiac surgery programs can function equally as well at a Veterans Administration hospital as at an affiliated university hospital. PMID- 3348735 TI - Comparative evaluation of prosthetic, reversed, and in situ vein bypass grafts in distal popliteal and tibial-peroneal revascularization. Veterans Administration Cooperative Study Group 141. AB - In 1983, the Veterans Administration initiated a cooperative study in 18 medical centers to perform a prospective comparative evaluation of vascular grafts. Five hundred ninety-six patients have had femoropopliteal below-knee or femorotibial peroneal (polytetrafluoroethylene, umbilical vein, in situ, or reversed saphenous vein) bypasses. Patency evaluation at two years revealed that for femoropopliteal below-knee reconstruction, the vein patency (76%) was better than prosthetic patency (64%). For femorotibial-peroneal reconstructions, the two-year patency for vein bypasses (73%) was significantly better than for prosthetic bypass grafts (30%). In general, the site of the distal anastomosis did not affect vein patency, but, with prosthetic bypasses, patency at two years progressively decreased with a more distal anastomosis. In situ and reversed saphenous vein bypasses had similar two-year patency for both femoropopliteal below-knee and femorotibial reconstructions. PMID- 3348737 TI - Splenectomy and the induction of murine colon cancer. AB - The influence of a functional spleen on induction and growth of cancer is unknown. Both beneficial and detrimental results have been observed in tumor bearing hosts following splenectomy. We examined the effect of splenectomy, splenic autotransplantation, and splenic preservation on the induction and growth of 1,2-dimethylhydrazine (DMH)-induced murine colon cancer. Following splenectomy there was a significant increase in malignant tumors but no increase in benign tumors. To rule out the possibility that splenectomy increased the carcinogenicity of DMH by decreasing the capacity for DNA repair in colon cells, the units of 06-alkylguanine DNA alkyltransferase were measured in tumor-free and malignant colon tissue from both splenectomized and control rats. This repair protein was chosen because it is known to protect cells from the mutagenic effects of methylating agents. There was no significant difference in the alkyltransferase activity of tumor-free colon vs malignant tumor or between treatment regimens. Thus, the ability of the spleen to protect rats from the induction of malignant colon tumors induced by DMH is most likely due to preservation of immunologic surveillance in the host. PMID- 3348738 TI - Heparin decreases ischemia-reperfusion injury in isolated canine gracilis model. AB - The mechanisms of ischemia-reperfusion injury in skeletal muscle remain controversial. Some investigators have demonstrated that heparin can ameliorate ischemic injury to heart, brain, and renal tissue. We investigated the ability of heparin sodium to decrease ischemia-reperfusion injury in an isolated gracilis muscle model in ten anesthetized mongrel dogs. One gracilis muscle was perfused normally while the contralateral muscle was subjected to six hours of ischemia followed by one hour of reperfusion. Five dogs were given a preischemic bolus of heparin sodium (200 U/kg, intravenously followed by a continuous infusion (15 U/kg/h, intravenously), and five control dogs received no heparin. Quantitation of skeletal muscle ischemia-reperfusion injury was determined by histochemical staining with triphenyl tetrazolium-chloride and computerized planimetry of the infarct size. Results from the ischemic muscle demonstrate a significant beneficial effect of heparinization. The nonheparinized dogs had a 72% +/- 5% infarct size, which was significantly reduced to 24% +/- 8% in the heparinized dogs. The mechanism of this protective effect may be due to heparin's anticoagulant, antiplatelet, or anti-inflammatory action. PMID- 3348739 TI - The changing epidemiology of pseudoaneurysm. Therapeutic implications. AB - To elucidate newly emerging trends in pseudoaneurysm causation, 57 patients with 81 pseudoaneurysms were reviewed. Only two (8%) of 24 pseudoaneurysms treated surgically before 1977 were infected, whereas 17 (30%) of 57 treated during the past decade were infected. There were four deaths among 12 patients (33%) with infected pseudoaneurysms compared with only one death among 45 patients (2%) with noninfected pseudoaneurysms. All five amputations were consequences of infected pseudoaneurysms. We conclude that (1) infection as a cause of pseudoaneurysm is increasing, (2) mortality and limb loss are now confined almost exclusively to cases involving infection, and (3) the current approach to pseudoaneurysm should include a high index of suspicion in patients at risk for infection, increased use of newer diagnostic scans, and an aggressive surgical attack on infected pseudoaneurysms that may require complete graft excision and extra-anatomic bypass. PMID- 3348740 TI - Extravasation. A serious complication of the split-sheath introducer technique for venous access. AB - The use of split-sheath introducers to place venous access catheters results in the potential for subcutaneous extravasation and tissue injury or necrosis. We present six cases that demonstrate this complication and illustrate the probable mechanism. The safe use of these catheters requires verification that blood can be aspirated from the catheter and a high index of suspicion for extravasation when symptoms develop. PMID- 3348741 TI - Cost of treating advanced leg ischemia. Bypass graft vs primary amputation. AB - We compared the hospital costs of 94 patients undergoing femoropopliteal bypass grafts with those of 53 patients undergoing primary amputation. The total cost of uncomplicated bypass surgery averaged +20,300, compared with +14,000 for uncomplicated below-knee amputation. However, including the cost of prosthesis and rehabilitation, the total cost of primary amputation was +20,400, equivalent to that of the bypass operation. Complications requiring revision of a bypass graft increased hospitalization by 4.5 days with the total cost rising to +28,700; complications that ended with major amputation added 15 hospitalization days and had an average cost of +42,200. In contrast, complicated below-knee amputation cost +40,600 and added 12.5 hospitalization days. There is therefore no cost-benefit in primary amputation when compared with arterial reconstruction, and cost should not be used to deny a patient the opportunity for limb salvage. PMID- 3348743 TI - Microbiological monitoring of aortic aneurysm wall and contents during aneurysmectomy. AB - Fifty-six patients, ranging in age from 49 to 90 years, underwent abdominal aortic aneurysmectomy and had cultures taken from the aneurysm wall and atheromatous debris to identify possible microbiological sources of future graft infection. All patients received antibiotics before and after operation. Eleven (19.6%) of 56 cultures yielded bacterial growth. The most common organism isolated was Staphylococcus epidermidis (in six of 11 patients). Thirty-seven percent of the aneurysms cultured were symptomatic (expanding or ruptured); however, this group accounted for 54% (6/11) of the positive cultures. During an average follow-up period of 24.5 months (range, four to 82 months), no early or late graft infections were documented. A literature review demonstrated the same disparity between positive cultures obtained at aneurysmectomy and subsequent low graft-infection rate. PMID- 3348742 TI - Revascularization of the external carotid artery. AB - Numerous reports describe the relative effectiveness of external carotid artery (ECA) revascularization in patients with ipsilateral internal carotid artery occlusion. Most, however, suffer from small numbers of patients or lack of detailed follow-up data. In addition, controversy persists regarding the safety with which this procedure can be performed. Twenty-two patients underwent a total of 27 ECA revascularizations. There were no perioperative strokes or deaths. During a mean follow-up period of 46 months, no strokes occurred and only two patients suffered transient ischemic attacks. Revascularization of the ECA is an effective means of treating the patient with ipsilateral internal carotid artery occlusion and may be performed with minimal morbidity and mortality. PMID- 3348745 TI - Subclavian vein catheterization. PMID- 3348746 TI - Regional vs general anesthesia. PMID- 3348744 TI - Total gastrectomy with left oblique abdominothoracic approach for gastric cancer involving the esophagus. AB - From January 1972 to December 1982, we performed 70 total gastrectomies with left oblique abdominothoracic approach for gastric cancer involving the esophagus. We emphasize that the diaphragm should be incised "U-shaped" from its origin to avoid respiratory tract failure due to phrenic nerve damage. Combined resection was performed in all cases either because of direct tumor invasion or because of lymph node dissection. Operative mortality occurred in only three cases (4.3%). There were nine cases (12.8%) of postoperative complications; in these cases, the complications were nonfatal. The five-year survival rates of patients were 60% in stage II, 27% in stage III, and 20% in stage IV, according to the Union Internationale Contre le Cancer-1978 staging classifications. PMID- 3348747 TI - Effect of ammonium chloride on the multiplication of infectious pancreatic necrosis virus. AB - The multiplication of IPNV in CHSE cells is inhibited by ammonium chloride. This inhibition is complete if NH4Cl is added early in the infective cycle. Immunofluorescence analysis shows that NH4Cl reduces the number of virus producing cells and thus suggests it may act by inhibiting virus internalization. In addition, NH4Cl can produce partial inhibition of IPNV multiplication if added later in the replicative cycle. Analysis of 3H-uridine incorporation into viral RNA shows that this later effect could be an inhibition of viral RNA synthesis. PMID- 3348748 TI - The interaction between native serum albumin and hepatitis B virus. AB - Purified hepatitis B virus particles were obtained from HBeAg positive serum by sucrose gradient ultracentrifugation and sephadex G-200 gel filtration. These virions formed a precipitation line in counterimmune electrophoresis with anti albumin antibody, but the reaction could be inhibited by anti-HBs. After two months at 4 degrees C, another precipitating line was formed under the same condition which could not be inhibited by anti-HBs and was, thus, due to free albumin. When that sample was incubated at 37 degrees C overnight, the line of free albumin disappeared. The virion bound albumin was monomeric in non denaturing gel electrophoresis. These results suggest that a reversible binding between virion and albumin may occur in vivo and does not require chemical modification or cross-linking. PMID- 3348749 TI - Prevalence of neutralising antibodies to Berne virus in animals and humans in Vellore, South India. Brief report. AB - In Southern India the prevalence of neutralising antibody to Berne virus was high in sera obtained from cattle (49%), horses (38%), and sheep (36%). Neutralising antibody was not detected in sera from humans and monkeys. PMID- 3348751 TI - Scanning electron microscopic studies of the nasal blood vessels. AB - Current histological and transmission electron microscopic techniques are insufficient for studying all different aspects of vascular morphology. As a result, we have used scanning electron microscopy (SEM) to examine nasal blood vessels. In our present studies the nasal septa of 15 rabbits were fixed by vascular perfusion, dried by the critical point method and coated with gold for SEM studies. Lower magnifications of specimens using this method show the tissue arrangement in the nasal septum. In higher magnifications the different vessels can be distinguished by their morphological features. The course of the vascular structures can be observed as well as the junctions between the different vessels. Our results indicate that different morphological techniques must be combined to understand the endonasal vasculature. PMID- 3348752 TI - The occurrence of capillary endothelial mitoses in the mesenchyme of the scala tympani during fetal development of the guinea pig. AB - Mitotic figures were found in the capillary endothelial cells of the cochleae of guinea pig fetuses, indicating a cellular proliferation. The significance of capillary sprouting in the mesenchyme beneath the basilar membrane a few days before opening of the scala tympani is discussed. PMID- 3348750 TI - Simultaneous investigations of elemental changes in individual cells of the stria vascularis and in endolymph. AB - Using the microprobe for energy dispersive X-ray microanalysis, the elemental compositions of both the individual cells of the stria vascularis and of the endolymph were followed simultaneously under normal conditions and after the administration of 120 mg/kg ethacrynic acid (EA). Marginal cells and intermediate cells showed reversible increases in potassium and decreases in sodium concentrations. Shifts in the ionic composition of endolymph occurred later than after elemental changes in the strial cells. The present results indicate that the marginal and the intermediate cells are the primary target for EA-induced ototoxicity. However, generalized toxic effects of EA are also indicated, with a general leakage of different elements occurring during the 30-60 min period after EA administration. PMID- 3348753 TI - Distribution of noradrenergic nerve fibers in canine nasal mucosa following selective neurectomies. AB - In this study, we have used noradrenergic histofluorescence and selective neurectomies of the vidian, ethmoid and caudal nasal nerves to evaluate the distribution of postganglionic sympathetic fibers in the canine nasal mucosa. In conjunction with the histochemical localization of the noradrenergic fibers in the nasal mucosa after vidian neurectomy, the norepinephrine content of the mucosa was also evaluated using high-performance liquid chromatography. Unilateral neurectomy of the superior cervical ganglion (SCG) resulted in the unilateral disappearance of all noradrenergic histofluorescence in the nasal mucosa, while no morphological changes in noradrenergic fibers could be identified after neurectomy of the cervical sympathetic trunk 1 cm below the SCG. Ethmoid neurectomy caused the disappearance of noradrenergic fibers of the upper third of the nasal mucosa, while vidian neurectomy resulted in a partial loss of noradrenergic fibers in the lower two-thirds of the nasal mucosa. The loss was chiefly in the area adjacent to venous sinusoids and was responsible for 50% of the norepinephrine content of this tissue. We concluded that all the postganglionic sympathetic fibers are from the ipsilateral SCG. Some of them travel via the ethmoid nerve and innervate the upper third of the nasal mucosa. The remaining fibers travel via the vidian nerve and perhaps the vessel walls of the supplying arteries and innervate the lower two-thirds of the nasal mucosa. The vidian nerve chiefly innervates the venous sinusoids of the lower two-thirds of the nasal mucosa. PMID- 3348754 TI - Effects of topical anesthetics on tympanic membrane structure. AB - Topical application of a local anesthetic agent can induce adequate insensibility to pain, and therefore can avoid the use of general anesthesia or invasive infiltration techniques for myringotomy or the insertion of a tympanostomy tube. A comparative study was conducted on a guinea pig animal model to determine the effects of three agents on the structure of the tympanic membrane: 5% tetracaine base dissolved in dimethylsulfoxide (DMSO), pure DMSO, and Bonain's solution. Survival times ranged from 1 day to 3 months. Following removal from the animals, membranes were embedded in Spurr and cut in semithin sections. Signs of mild or severe external otitis were frequent; to avoid non-specific results, infected specimens were not evaluated. Bonain's solution caused loss of the epidermis and mucosal epithelium within 1 day of treatment. The connective tissue layers of the drum were severely hyperplastic after a survival time of 1 month. Tetracaine base in DMSO caused a loss of epithelium and mucosal cells in 3 days. Regeneration started within 7 days and a restitution to integrity was seen after 3 months in drums treated with tetracaine base or DMSO alone. PMID- 3348755 TI - Bell's palsy and its recurrences. AB - The purpose of this study was to evaluate the incidence and the prognosis of patients with recurrences of Bell's palsy. Yanagihara's classification of recurrent palsies was used, and all palsies were separated into five different types. A total of 304 patients with Bell's palsy were examined. The recurrent ipsilateral attacks (i.e., the unilateral recurrent palsies) showed a worse prognosis when compared with the non-recurrent palsies. In contrast, the recurrent attacks involving the contralateral facial nerve (bilateral alternating palsies) presented a better facial recovery. In reviewing the recurrent cases, the stapedial reflex demonstrated no prognostic value. Our results suggest that in presenting data of Bell's palsy it is advisable to differentiate the recurrences from the common (non-recurrent) palsies. PMID- 3348756 TI - George Lyman Duff memorial lecture. Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry. AB - This review summarizes the evidence that the physical properties of lipids which accumulate in the intima play major roles in the progression and regression of lesions of atherosclerosis. All of the three major classes of lipids that accumulate in lesions (phospholipids, cholesterol, and cholesterol esters) are water insoluble. Phospholipids and cholesterol esters are almost mutually insoluble, but cholesterol, a crystalline solid at 37 degrees C, has considerable solubility in phospholipid bilayers and cholesterol esters. In normal infant intima, cholesterol is solubilized by phospholipid membranes. During fatty streak development, groups of cells are stimulated to take up more cholesterol than they excrete. The excess cholesterol is biochemically converted to cholesterol ester, which separates as droplets to form foam cells. Some fatty streaks then undergo a transition to an intermediate lesion containing excess cholesterol which is carried in cholesterol-supersaturated membranes and droplets. When nucleation of this excess cholesterol occurs, it precipitates as crystals; their formation coincides with the onset of necrosis and plaque formation. The hallmark of plaque is the presence of inert cholesterol crystals. They appear to form from hydrolysis of the older deposits of cholesterol esters in the base of intermediate lesions. Thus, the lipids in plaques are stratified, with recently deposited cholesterol esters present in the luminal part of the intima and older deposits in the deeper regions. When plasma cholesterol is lowered below about 150 mg/dl, lipids are mobilized from lesions and regression gradually occurs. Early in the regression process, cholesterol esters are reduced at least partly by hydrolysis to yield cholesterol, some of which may crystallize and inhibit rapid regression. After prolonged periods of low plasma cholesterol, cholesterol esters and foam cells disappear and crystalline cholesterol gradually dissolves, leading to true regression. PMID- 3348757 TI - Coordinate changes in levels of human serum low and high density lipoprotein subclasses in healthy men. AB - Measurement of serum lipoproteins by analytic ultracentrifugation revealed significant correlations involving subfractions of low density (LDL) and high density (HDL) lipoproteins in 81 men studied cross-sectionally at baseline and longitudinally during a 1-year exercise trial. One-year changes in lipoprotein levels in 38 exercising men and in 30 sedentary controls showed correlations that paralleled those observed at baseline. Positive correlations observed between plasma levels of larger, more buoyant LDL of flotation rate (Sof) 7 to 10 (LDL-I) and HDL2 may be due to processes that also coregulate changes in levels of these lipoprotein subclasses. Similarly, positive correlations among smaller, more dense LDL of Sof 2 to 6 (LDL-III), IDL, and HDL3 suggest that levels of these lipoprotein species are also coordinately regulated. An inverse correlation of change in LDL-I with change in LDL-III raises the possibility of precursor product relationships between LDL in these categories. Thus, changes in lipoproteins which are related to coronary disease risk are not independent of one another, and the development of coronary disease may be influenced by processes linking the metabolism of individual IDL, LDL, and HDL components. PMID- 3348758 TI - Mortality and cholesterol metabolism in familial hypercholesterolemia. Long-term follow-up of 96 patients. AB - The aim of this prospective study was to explore the association of different prognostic factors including parameters of cholesterol metabolism with coronary morbidity and mortality in a study group of 96 patients who were heterozygous for familial hypercholesterolemia. During a 15-year follow-up period, 27% of the patients (44% of the men and 10% of the women, p less than 0.01) died from coronary disease, and an additional 4% died of noncoronary causes. Of the baseline characteristics, male gender, previous myocardial infarction, and smoking were the classical risk factors significantly associated with poor cardiac prognosis. In addition, a low bile acid synthesis predicted enhanced coronary mortality both in univariate and multivariate analysis, and in men bile acid synthesis was significantly correlated with cardiac mortality. Further analysis indicated that also in subjects without baseline myocardial infarction, low bile acid, cholesterol synthesis, or both predicted increased risk of coronary events. In multivariate analysis, male gender, previous myocardial infarction, and low bile acid synthesis at baseline explained 5%, 15%, and 5% (25%), respectively, of the variability of survival. Age, serum total cholesterol, and triglyceride values were unrelated to survival. PMID- 3348759 TI - Dietary factors relate to cardiovascular risk factors in early life. Bogalusa Heart Study. AB - Relationships between diet and cardiovascular disease risk factors were studied in a cohort of infants in Bogalusa, Louisiana. The 24-hour dietary recalls and cardiovascular measurements were obtained on each child at age 6 months, yearly through age 4, and again at age 7 (cardiovascular measurements only). At ages 4 and 7, children with persistently high intakes of dietary cholesterol (three or more measurements in the upper tertile) had levels of serum total cholesterol approximately 14 mg/dl higher than children whose intakes of cholesterol were not persistently high. Children in the upper tertile for dietary cholesterol had levels of low density lipoprotein cholesterol (15 mg/dl at age 4 and 18 mg/dl at age 7) higher than children in the lower tertile for dietary cholesterol. Children with high intakes of animal fat were 2 to 6 kg heavier (p less than 0.05) than those with lower intakes. Changes in dietary cholesterol correlated significantly with changes in serum total cholesterol (r = 0.42) and low density lipoprotein cholesterol (r = 0.50) from 6 months to 4 years of age. Changes in subscapular skinfold measurements correlated significantly with changes in intake of total protein (r = 0.31), total fat (r = 0.25), starch (r = 0.31), and energy (r = 0.39) from ages 6 months to 4 years. Results indicate that tracking of dietary components and their relationships with cardiovascular disease risk factors can be detected at an early age. These findings may well be the groundwork for later studies of obesity and the early onset of hyperlipoproteinemia. PMID- 3348761 TI - Making ethical decisions: a nursing right. PMID- 3348760 TI - Fibronectin in platelet adhesion to human collagen types I and III. Use of nonfibrillar and fibrillar collagen in flowing blood studies. AB - Platelet deposition at high wall shear rates on collagen type I and type III purified from human umbilical arteries is dependent on the presence of fibronectin and von Willebrand factor (VWF). The role of fibronectin at low wall shear rates (less than or equal to 500 s-1), where platelet deposition was independent of VWF, was studied with purified collagen I and III. Platelet deposition on nonfibrillar collagen I was fibronectin-dependent at all wall shear rates. Platelet deposition on nonfibrillar collagen type III was fibronectin dependent at 300 s-1 and higher shear rates. By using a mixture of nonfibrillar type I and III, platelet deposition was found to be fibronectin-dependent at the tested wall shear rates (20, 100, and 300 s-1). This dependency was less than with nonfibrillar type I only, but more than with nonfibrillar type III. For platelet deposition on reconstituted type I or type III collagen fibrils, no fibronectin dependency was observed up to the highest wall shear rate tested (1800 s-1). The same results were obtained with a mixture of native type I and III fibrils. Thus, the dependence of platelet deposition on fibronectin is determined by the collagen type and the wall shear rate. The dependence on the fibronectin concentration was tested with nonfibrillar collagen type I at a wall shear rate of 300 s-1. Platelet deposition increased with increased fibronectin concentration up to a level of 700 micrograms/ml and leveled off above this concentration. PMID- 3348762 TI - Continuous subcutaneous infusion: flexible option in symptom control. PMID- 3348763 TI - Nutritional support for sick children. 2nd symposium 'Progress in Infantile Nutrition'. Naples, January 30-31, 1987. Proceedings. PMID- 3348764 TI - [Textural changes in the bronchial mucosa of the horse. A contribution to the structure of the bronchial basement membrane]. PMID- 3348765 TI - [Current prevention and therapy of atrophic rhinitis in swine with special reference to pathogen resistance]. PMID- 3348766 TI - [New areas of use of a dry chemical analysis system. 2. Determination of lactate dehydrogenase in cow's milk]. PMID- 3348767 TI - [Morphometric studies of the dog femur]. PMID- 3348768 TI - Biosynthetic pathways for the Leb and Y glycolipids in the gastric carcinoma cell line KATO III as analyzed by a novel assay. AB - The biosynthetic pathways for the difucosylated type 1 and 2 glycolipids, Leb and Y, respectively, were investigated in the gastric carcinoma cell line KATO III, using a novel chromatogram binding assay. The type of fucosylation obtained was deduced from the binding pattern of monoclonal antibodies specific for the biosynthesized glycolipid products using microsomal fractions as the source of enzyme, pure glycolipids and non-radioactive GDP-fucose as acceptor and donor substrates, respectively. The Leb glycolipid (Fuc alpha 1----2Gal beta 1--- 3GlcNAc(4----1 alpha Fuc) beta 1----3LacCer) was synthesized mainly via the blood group H, type 1, precursor (Fuc alpha 1----2Gal beta 1----3GlcNAc beta 1--- 3LacCer). However, the Lea glycolipid (Gal beta 1----3GlcNAc(4----1 alpha Fuc)beta 1----3LacCer) also served as a precursor for the alpha 1----2 fucosyltransferase, thus allowing conversion of Lea to Leb. This biosynthetic route represents either an "aberrant" specificity of the Fuc alpha 1----2 transferase associated with these gastric carcinoma cells and/or a new member of the alpha 1----2 fucosyltransferase family. The Y glycolipid (Fuc alpha 1----2Gal beta 1----4GlcNAc(3----1 alpha Fuc)beta 1----3LacCer) was synthesized exclusively via the classical pathway using the blood group H type 2 glycolipid (Fuc alpha 1- --2Gal beta 1----4GlcNAc beta 1----3LacCer) as precursor. The X glycolipid (Gal beta 1----4GlcNAc(3----1 alpha Fuc)beta 1----3LacCer) did not serve as an acceptor substrate for the alpha 1----2 fucosyltransferase(s) present. The use of non-radioactive sugar-nucleotides as donor substrate, defined glycolipid precursors as acceptor substrates and of specific monoclonal anti-glycolipid antibodies for detection provides a rapid and highly specific assay for analyzing biosynthetic pathways of glycosyltransferases. PMID- 3348770 TI - Growth hormone dependent stimulation of osteoblast-like cells in serum-free cultures via local synthesis of insulin-like growth factor I. AB - Gene-recombinant human growth hormone (rhGH) elicited a dose-dependent stimulation of the proliferation of osteoblast-like cells (OB), when grown in strictly serum-free longterm cultures. A half-maximal effect was observed at concentrations of 15-20 ng/ml and the maximal stimulation was 160% of hormone free controls. The rhGH-induced effect on proliferation could be inhibited dose dependently by the addition of an insulin-like growth factor (IGF) I-antiserum to the medium. Moreover, IGF I and rhGH had additive effects only when the exogenous IGF I concentration exceeded that of endogenously produced IGF I by a large margin. Thus, direct stimulation of OB proliferation by rhGH is, at least in part, mediated by IGF I-like immunoreactivity. PMID- 3348771 TI - Simultaneous observation of positive and negative nuclear Overhauser effects in oligopeptides due to segmental motion. AB - Nuclear Overhauser effect (NOE) studies of the symmetrical cystine peptides (Formula: see text) (n = 1-3) in dimethylsulfoxide, have resulted in the simultaneous observation of both positive and negative NOEs. Positive NOEs are observed on the Trp C2H and C4H protons of the indole ring upon irradiation of Trp C alpha H and C beta H2 resonances in the peptides where n = 1 and 2. Negative NOEs are observed between backbone NH and C alpha H protons. The magnitudes of the observed NOEs are sensitive to changes in molecular size and solvent viscosity. The results demonstrate that NOEs may be a useful probe of sidechain segmental motion in oligopeptides. PMID- 3348769 TI - Enzymatic formation and chemical synthesis of an active metabolite of 3 beta hydroxy-5 alpha-cholest-8(14)-en-15-one, a potent regulator of cholesterol metabolism. AB - The enzymatic (rat liver mitochondria) conversion of 3 beta-hydroxy-5 alpha cholest-8(14)-en-15-one to 5 alpha-cholest-8(14)-ene-3 beta,26-diol-15-one is described. The enzymatic product was judged, on the basis of IH and 13C NMR studies, to be a 4:1 mixture of its 25R and 25S isomers. (25R)-5 alpha-Cholest 8(14)-ene-3 beta,26-diol-15-one was prepared through a five-step synthesis from (25R)-26-hydroxycholesterol. The (25R) isomer of the new compound was found to be highly active in the suppression of the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells and to inhibit the esterification of cholesterol in jejunal microsomes. PMID- 3348772 TI - Evidence for novel 30,000-50,000Mr cofactor in the activation of muscle. AB - A new approach is described for reconstituting a fully desensitized skeletal muscle fiber to restore its contractility. These studies revealed a novel regulatory cofactor, 30-50,000Mr by filtration (26-55kDa by SDS PAGE). It was shown to be critical for the Ca2+-activation in the physiological milieu. The cofactor was present in skeletal and cardiac muscles as well as in brain, but not in kidney and liver. The cofactor may be a second Ca2+ switch in a dual regulation scheme for vertebrate muscle, or could provide an essential link in the cross-bridge cycle beyond activation. PMID- 3348773 TI - Infection of human hematopoietic progenitor cells using a retroviral vector with a xenotropic pseudotype. AB - In an effort to determine if viral envelope type influences the infectivity of human hematopoietic progenitor cells with retroviral vectors, we have pseudotyped the retroviral vector N2, which confers G418-resistance, in either an amphotropic or xenotropic envelope. Vector titres obtained by the pseudotype procedure were nearly two orders of magnitude lower than the titer obtained when N2 was packaged using the amphotropic PA317 packaging cell line. Despite its low titer, xenotropically pseudotyped N2 generated G418-resistant hematopoietic colonies at levels approaching those observed after bone marrow was infected using vector packaged using PA317 cells. These results suggest that manipulations of vector envelope may lead to improvements in the level of infection of human hematopoietic stem cells. PMID- 3348774 TI - Hyaluronic acid synthesis and secretion by rat liver fat storing cells (perisinusoidal lipocytes) in culture. AB - The ability of rat liver fat storing cells to synthesize and to secrete hyaluronic acid was examined in monolayer cultures. The cells produce [3H] glucosamine-labeled hyaluronic acid, of which about 80% are secreted into the medium. The synthesis rate per cell (mg DNA) of labeled total glycosaminoglycans and hyaluronic acid in the medium increases significantly with culture time, but hyaluronic acid expressed as fraction of total glycosaminoglycans declines from about 0.70 in early cultures (up to the 4th day) down to 0.20 in advanced cultures. Cycloheximide increases and beta-D-xylopyranoside decreases significantly the fraction of hyaluronic acid in the medium, colchicine up to 5 microM was without effect. The synthesis of hyaluronic acid is a newly recognized function of this special type of sinusoidal liver cells. The results suggest that fat storing cells are likely to be a major source of hyaluronic acid in normal and probably also in injured liver. PMID- 3348775 TI - Expression of erythroid differentiation factor (EDF) in Chinese hamster ovary cells. AB - Plasmid DNA containing EDF subunit cDNA and mouse dihydrofolate reductase (DHFR) cDNA was transfected into CHO DHFR- cells by the calcium-phosphate method. DHFR positive transformants secreted recombinant EDF (r-EDF) constitutively in an active form and accumulated it in the conditioned medium. Furthermore, cells which were resistant to methotrexate (MTX : 0.5 microM) secreted r-EDF up to 1 microgram/ml. r-EDF was identical to natural EDF (n-EDF) produced by human acute monocytic leukemia cell line, THP-1, as regards its dimeric structure and a biological activity. PMID- 3348776 TI - Protein phosphorylation and activation of human platelets by sodium fluoride. AB - The ability of sodium fluoride (NaF) and thrombin to stimulate aggregation and protein phosphorylation in intact human platelets was measured and compared. When platelets were stimulated by NaF, phosphorylation of the 20 KDa protein was transient and after 5-10 min returned to the same level as that of unstimulated cells. On the other hand, 47 KDa protein was slowly phosphorylated without obvious dephosphorylation. The slow activation of the 47 KDa protein phosphorylation correlated well with the time required for the aggregation and secretion. Phosphoamino acid analysis showed that the phosphorylated amino acids of the 47 KDa protein from platelets activated by NaF and thrombin were slightly different. These results suggest that different stimuli may lead to the same protein phosphorylation by different biochemical mechanisms of action. PMID- 3348777 TI - Two distinct succinate thiokinases in both bloodstream and procyclic forms of Trypanosoma brucei. AB - Two succinate thiokinase activities specific for either adenine or guanine nucleotides have been found in Trypanosoma brucei. Key glycolytic and citric acid cycle enzymes were measured to show repression of glycolysis and derepression of the citric acid cycle in the procyclic form, relative to the bloodstream form. A marked rise in adenine-linked succinate thiokinase activity accompanied a rise in activity of citric acid cycle enzymes. However, guanine-linked succinate thiokinase was found to increase only slightly in activity. These results implicate the adenine-linked enzyme as an essential component of the citric acid cycle, whereas the guanine-linked enzyme appears to be under separate control. This communication also reports for the first time the occurrence of citrate synthase activity in the bloodstream (long slender) form of T. brucei. PMID- 3348778 TI - Alkyl-linked diglycerides inhibit protein kinase C activation by diacylglycerols. AB - Alkylacylglycerols are synthesized when choline-phospholipids are degraded by a phospholipase C. This class of compounds has been shown to have biological activities; however, the mechanism of action is unknown. A series of alkyl-linked diglycerides were synthesized and tested for activity in an in vitro assay for protein kinase C. When protein kinase C activity was stimulated with the synthetic diacylglyceride analog 1-oleoyl-2-acetyl-sn-glycerol, the addition of alkyl glycerides caused a concentration-dependent inhibition of protein kinase C activity. Comparison of the protein kinase C inhibition by this series of 1-O alkyl-2-acyl analogs revealed that both saturated and unsaturated long-chain groups in position 1 were effective and that dietherglycerols with short-chain moieties in position 2 were also effective. It is concluded from these studies that the biological activity of alkyl-linked glycerides may be expressed through protein kinase C inhibition. PMID- 3348779 TI - The effect of iron overload on the mitochondrial porphyrin level in the hexachlorobenzene induced experimental porphyria. AB - Liver mitochondria isolated from rats treated with hexachlorobenzene plus iron, present a lower content of total porphyrin in respect to that of mitochondria from rats fed hexachlorobenzene alone. The in vitro mitochondrial porphyrin accumulation processes have been studied in mitochondria from iron loaded rats. It has been found that under these conditions the active porphyrin uptake process, which is driven by the K+ transmembrane gradient, is maximally inhibited in the presence of pentachlorophenol at a concentration similar to that found in vivo in the hexachlorobenzene experimental porphyria. By contrast the same degree of inhibition is presented by control mitochondria only in the presence of pentachlorophenol plus valinomycin, a condition which collapses the transmembrane K+ gradient. A strict correlation between porphyrin uptake and K+ concentration has been found in control as well as in iron treated mitochondria. A possible involvement of peroxidative reactions in the mitochondrial membranes has been proposed as a cause of the changes in the permeability properties of the mitochondrial membranes in the experimental chronic hepatic porphyria under conditions of iron overload. PMID- 3348780 TI - Desensitization to norepinephrine includes refractoriness of calcium release in myocardial cells. AB - Localization of myoplasmic free calcium was measured in fura2-loaded single rat myocardial cells to determine whether the mechanism of norepinephrine desensitization includes redistribution of calcium. Fluorescence intensities at each pixel were quantitated by use of a photon-counting, microchannel plate camera. From these images, values of calcium-dependent fluorescence intensity averages in whole cells, areas of calcium release (as zones of high intracellular calcium concentrations), and ratios of fluorescence intensity in central vs. peripheral sites were determined. Stimulation by 1 nM norepinephrine caused an increase in total free intracellular calcium and an activation of intracellular calcium release sites from subsarcolemmal pools initially and later from centrally located calcium pools. Subsequent addition of 100 nM norepinephrine failed to cause significant intracellular calcium release from centrally located pools. In contrast, forskolin exposure still released high concentrations of calcium from these central pools. These results indicate that pretreatment with even a relatively small concentration of norepinephrine causes markedly decreased subsequent intracellular calcium release from centrally located sarcoplasmic reticulum because of a refractoriness of the link between receptor activation and calcium release. PMID- 3348781 TI - Phosphorylation of platelet actin binding protein protects against proteolysis by calcium dependent sulfhydryl protease. AB - When Actin Binding Protein (ABP) isolated from human blood platelets is phosphorylated in vitro with a cyclic AMP dependent kinase it becomes resistant to proteolysis by the Calcium Dependent Sulfhydryl Protease (CDSP). This protection against proteolytic cleavage is specific for CDSP since phosphorylation of ABP does not protect against proteolysis by trypsin, papain and thermolysin. Thus, there appears to be a distinct phosphorylation site on the ABP molecule which is essential for regulating the initial proteolytic degradation of ABP by CDSP. PMID- 3348782 TI - Isolation and characterization of insulin receptors from rat kidney glomeruli and tubules. AB - In order to directly compare the structural characteristics of renal glomerular and tubular insulin receptors, the purified isolated nephron subunits were extracted with 1% Triton X-102, fractionated by DEAE-Sephacel ion exchange column chromatography and the fractions containing insulin binding proteins were identified by the precipitation of 125I-insulin-protein complexes with polyethylene glycol (PEG). The fractions containing insulin binding proteins were pooled, incubated with 125I-insulin and covalently cross-linked with disuccinimidyl suberate, followed by chromatography of the cross-linked samples on Sepharose CL-6B. From both glomeruli and tubules, three 125I-insulin-binding complexes with molecular weights of 560 KDa, 220 KDa and 95 KDa were found. SDS PAGE of these complexes from glomeruli and tubules under both reducing and nonreducing conditions gave similar patterns of 125I-insulin-crosslinked components, with the exception of the polypeptide pattern from the 560 KDa peak fraction which was markedly different between glomeruli and tubules with the former giving major labeled components at 170 and 68 KDa while the latter showed labeled components of 125 KDa and greater than 250 KDa. Glomerular and tubular insulin receptors, therefore, display similar subunit composition under reducing conditions, but differ in the non-reduced state, suggesting that these complexes may differ in the extent and/or nature of disulfide bonding. PMID- 3348783 TI - The cDNA of cucumber mosaic virus-associated satellite RNA has in vivo biological properties. AB - Two isolates of cucumber mosaic virus (CMV)-associated satellite RNA, differing in their biological properties, have been reverse transcribed. One was able to induce the tomato necrotic syndrome whereas the other one attenuated fernleaf symptoms on tomato plants after co-inoculation with the helper virus. cDNAs representing partial or full-length copies have been cloned in the plasmid pAT 153 and sequenced. The two RNAs showed a very limited number of variations (2 to 5 substitutions depending on the clones and a one base deletion). Full-length cDNA copies possessed the same biological properties that characterized the parent satellite RNA. Efficiency of the cDNA depended upon its form in the inoculum (circular or linear plasmid or excised cDNA) and upon the form of the helper virus (viral RNAs or virions) with which it seemed to compete for installation and/or expression. PMID- 3348785 TI - Enhancement of lectin-induced cap formation in human neutrophils by cyclosporin A. AB - Cyclosporin A, a potent immunosuppressive agent, has been extensively studied for its immunomodulatory effects on T-cells. Recently Cyclosporin A has been shown to cause renal damage, which correlates with increased glomerular neutrophil migration. The precise role of Cyclosporin A on neutrophil function has not been established. In this study we investigated the role of Cyclosporin A in the regulation of cap formation in human neutrophils. Our results show an increased concanavalin A-induced cap formation in human neutrophils pretreated with Cyclosporin A, implicating a possible role of Cyclosporin A in human neutrophil activation. The correlation between enhanced capping, renal nephrotoxicity and neutrophil migration remains to be studied. PMID- 3348784 TI - Release of oligosaccharides possessing reducing-end N-acetylgalactosamine from mucus glycoprotein in Streptomyces sp. OH-11242 culture medium through action of endo-type glycosidase. AB - A crude enzyme preparation from a culture medium of Streptomyces sp. OH-11242 contained endo-alpha-N-acetylgalactosaminidase activity. The activity could be induced by the addition of purified porcine gastric mucin to the culture medium. Oligosaccharides corresponding to approximately 2-14 glucose units were detected in the culture medium and also in an incubated reaction mixture of crude enzyme preparation and mucus glycoprotein. The resulting product with N acetylgalactosamine at the reducing terminal implied the presence of a new type of endo-glycosidase liberating not only Gal beta 1-3GalNAc but also other larger oligosaccharides by hydrolysis of the O-glycosidic linkage between GalNAc and Ser (Thr). PMID- 3348786 TI - Strain-specific occurrence of two ornithine decarboxylase species in mouse kidney. AB - Ornithine decarboxylase in the crude extract from the kidney of androgen-treated mice was labeled by reaction with radioactive alpha-difluoromethylornithine and analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis followed by autoradiography. Two species of ornithine decarboxylase with molecular weights of 54,000 and 52,000 were observed in the crude extracts from BALB, C57BL, C58, SJL, and dd mice but only the species with a molecular weight of 54,000 was observed in the crude extracts from AKR and C3H mice, indicating strain-specific occurrence of at least two species of mouse ornithine decarboxylase. PMID- 3348787 TI - 1,2-Dioctanoyl-glycerol induces a discrete but transient translocation of protein kinase C as well as the inhibition of MCF-7 cell proliferation. AB - Exposure of MCF-7 human breast cancer cells to phorbol esters such as 12-0 tetradecanoylphorbol-13-acetate (TPA) results in a dose-dependent inhibition of cell proliferation. One of the earliest biochemical events induced by TPA is the translocation of protein kinase C from the cytosolic to the particulate compartment. We have investigated the effects of permeant diacylglycerol 1,2 dioctanoyl-glycerol (diC8) on both protein kinase C activity and MCF-7 cell proliferation. DiC8 induces a discrete but significant translocation of protein kinase C within the first minutes of MCF-7 cell treatment (26 +/- 6%, mean +/- SD of 5 different experiments, upon 5 min incubation in the presence of 43 micrograms/ml diC8). However, this effect is only transient as the enzymatic activity returns to the control value after 60 min. DiC8 mimics the effect of TPA on MCF-7 cell proliferation. The dose-response curves for both protein kinase C translocation and cell growth inhibition show that diC8 exerts its effects on both parameters in the same range of concentrations, despite some discrepancies at the lowest doses. We also report that long-term treatment of the cells with diC8 does not lead to the protein kinase C disappearance observed during prolonged exposure to TPA. All together, our results reinforce the hypothesis of a negative modulatory role of protein kinase C in MCF-7 cell proliferation and suggest that the enzyme translocation but not its down-regulation could be a pre requisite in the biological cell response. PMID- 3348788 TI - A soluble angiotensin II-binding protein from rabbit liver. AB - An angiotensin II-binding activity has been detected in the 100,000 x g supernatant fraction of rabbit liver. The total amount of binding activity in this fraction was substantially greater than that which could be solubilized from hepatic particles by treatment with digitonin. The crude soluble binding activity resembled the binding protein which had been purified from the particles in several respects. First, binding required the presence of p chloromercuriphenylsulfonic acid and bound angiotensin II was released by dithiothreitol. Second, the molecular weight of the responsible protein cross linked to radioiodinated angiotensin II was about 75,000 in the reduced, denatured state. Finally, guinea pig antiserum raised against the binding protein that had been purified from particles reacted identically with the soluble and solubilized activities. PMID- 3348789 TI - Partial characterization of a low molecular weight proteoglycan isolated from bovine parietal pericardium. AB - Knowledge of the nature of pericardial connective tissue components is incomplete. To gain a better understanding of the composition of this tissue, bovine parietal pericardium was extracted with 4 M guanidine hydrochloride yielding a proteoglycan-containing protein mixture. This was fractionated by a three-step chromatographic procedure with the resultant purification of a 75-110 Kd proteoglycan. The purified proteoglycan was susceptible to chondroitinase ABC digestion but resistant to chondroitinase AC and nitrous acid degradation suggesting the presence of dermatan sulfate glycosaminoglycan(s). This is the first reported isolation of a proteoglycan from parietal pericardium. PMID- 3348790 TI - A method for specific cloning and sequencing of human hprt cDNA for mutation analysis. AB - A method has been developed for the specific amplification and cloning of human hprt cDNA which can be used for mutant sequence analysis. Messenger RNA is isolated from TK6 lymphoblasts and is used to produce a first strand cDNA with reverse transcriptase primed with oligo dT. Second strand synthesis and subsequent amplification of hprt sequences is accomplished using Thermus aquaticus DNA polymerase and hprt-specific primers in the polymerase chain reaction (PCR) procedure. Convenient restriction enzyme sites have been built into the 5' ends of the PCR primers to allow cloning of the hprt fragments in M13mp19. Dideoxy sequencing of hprt with specific primers can be carried out using either the PCR reaction product or fragments cloned in M13mp19 as substrate. This general cloning/sequencing method can be used to analyze hprt mutation in human cells obtained both in vitro and in vivo. PMID- 3348791 TI - Formation and metabolism of hepoxilin A3 by the rat brain. AB - Incubation of homogenates of the rat cerebral cortex with arachidonic acid led to the appearance of hepoxilin A3, analysed as its stable trihydroxy derivative, trioxilin A3, by high resolution gas chromatography/electron impact mass spectrometry. Using the stable deuterium isotope dilution technique, it is estimated that the cerebral cortex generates 5.0 +/- 0.2 ng/mg protein of hepoxilin A3. The formation of this product was stimulated by the addition of exogenous arachidonic acid (12.9 +/- 1.5 ng/mg protein) and blocked by boiling of the tissue. Addition of the dual cyclooxygenase/lipoxygenase inhibitor BW 755C at a concentration of 75 microM did not result in a blockade of hepoxilin formation. Three other regions were also tested for their ability to form hepoxilin A3 upon stimulation with exogenous arachidonic acid, i.e. median eminence, 11.7 +/- 1.6 ng/mg protein, pituitary, 12.3 +/- 0.7 ng/mg protein; pons, 26.6 +/- 0.2 ng/mg protein. In a separate study, 14C-labelled hepoxilin A3 was transformed into 14C labelled trioxilin A3 by homogenates of the rat whole brain, demonstrating the presence of epoxide hydrolases in the CNS which utilise the hepoxilins as substrates. This is the first demonstration of the occurrence of the hepoxilin pathway in the central nervous system. PMID- 3348792 TI - A new facile trinitrophenylated substrate for peptide alpha-amidation and its use to characterize PAM activity in chromaffin granules. AB - Carboxyl terminal alpha-amidation is a prevalent post translational modification in neuropeptide hormones, with amidation being essential for biological activity. We report a direct demonstration and characterization of peptidyl alpha-amidating monooxygenase (PAM) activity in chromaffin granules, secretory vesicles long known as loci for synthesis and storage of catecholamines but only recently recognized as processing and storage sites for neuropeptides. This finding, together with the recently recognized competence of dopamine-b-monooxygenase to carry out N-dealkylation, provides important information regarding the co localization and co-secretion of multiple neuromodulators. In addition, we introduce a new substrate for both pituitary and chromaffin granule PAM--TNP-D Tyr-Val-Gly. This substrate exhibits high turnover, and has the important advantage of allowing quantitative activity determinations using standard spectrophotometric techniques, thus facilitating mechanistic studies and inhibitor development. PMID- 3348793 TI - Photodynamic toxicity of porphyrins and chlorins for a human tumor cell line: combined light and concentration dose responses for the retained fraction. AB - In recent years porphyrins and related materials have been tested as antitumor agents. A technique was devised to obtain dose-response curves for the sensitizer fraction that resists one day of elution by tissue culture medium--the retained fraction. We found a steep "threshold" dose response relationship that helps to explain tumor destruction without damage to normal tissues. The family of dose response curves produced by a wide range of light exposures suggests that chlorins and porphyrins do not act by identical mechanisms. Moreover, they suggest that chlorins will prove superior in practical use. PMID- 3348794 TI - Early effects of retinol and retinoic acid on protein synthesis in retinol deficient rat testes. AB - When an [35S] labeled mixture of methionine and cysteine was injected intratesticularly into retinol-deficient rats, two hours later more than 980 cytosolic proteins were detected by computer aided two dimensional gel electrophoresis. Furthermore, two hours after oral refeeding retinyl acetate as the source of retinol to retinol deficient rats, synthesis of 286 proteins was inhibited and that of 101 proteins was activated. Refeeding with retinoic acid leads in two hours to even higher inhibition of protein synthesis and the labeling patterns of proteins are not identical when compared to retinol refed rats. The results indicate that retinol or retinoic acid quickly influence expression of many proteins and suggest that retinol action in the testes is not identical to that of retinoic acid. PMID- 3348795 TI - Haloketone transition state analog inhibitors of cholesterol esterase. AB - The cholesterol esterase-catalyzed hydrolysis of p-nitro-phenyl butyrate is reversibly inhibited by four phenyl haloalkyl ketones. Inhibitor potency is greatest for halogenated acetophenones and parallels the extent of hydration of the various ketones in buffered D2O. These results are consistent with an inhibition mechanism wherein haloketones reversibly form hemiketal adducts at the active site that structurally mimic tetrahedral intermediates of the cholesterol esterase catalytic cycle. PMID- 3348796 TI - Use of rhodamine 123 to investigate alterations in mitochondrial activity in isolated mouse liver mitochondria. AB - The fluorescent dye Rhodamine-123, which selectively stains mitochondria depending on the mitochondrial membrane potential, was used with flow cytometry to evaluate alterations in activity of mitochondria isolated from mouse liver. Under in vitro conditions, with succinate and ADP present in the buffer, mitochondrial activity was affected by a variety of metabolic inhibitors that modify membrane potential. These results demonstrate clearly that flow cytometric techniques using Rhodamine-123 can be employed to study activity in isolated mitochondria. PMID- 3348797 TI - Amiloride sensitive activation of S6 kinase by angiotensin II in cultured vascular smooth muscle cells. AB - Angiotensin II was shown to activate S6-kinase in cultured vascular smooth muscle cells (VSMC) in a dose- (10(-9)-10(-6) M) and time-dependent manner. Pretreatment of quiescent cells with 12-O-Tetradecanoylphorbol-13-acetate had no effect on the activation levels of the kinase at the hormone levels used. However, stimulation of S6-kinase activity by angiotensin II was markedly inhibited by the inclusion of amiloride hydrochloride in serum-free medium during activation procedures. Angiotensin was not mitogenic for VSMC at even the highest doses used (10(-6) M). These findings support the notion that raised intracellular pH results in the activation of protein synthesis in quiescent cells. PMID- 3348798 TI - 31P NMR measurements of myocardial pH in vivo. AB - A 31P NMR magnetization transfer method for measuring myocardial pH in vivo is demonstrated in the lamb, dog and cat. The method involves measuring the difference in chemical shift between the resonances of phosphocreatine and inorganic phosphate in magnetization transfer difference spectra in which the gamma-phosphate resonance of ATP has been saturated. The method has been verified by measuring the chemical shift difference between the resonances of 2 deoxyglucose 6-phosphate and phosphocreatine following infusion of the animals with 2-deoxyglucose. The measured pH values are significantly lower than those obtained in previous studies on the heart in vivo. PMID- 3348799 TI - Prevention of the TPA-mediated down-regulation of protein kinase C. AB - Protein kinase C activity in lymphocytes was down-regulated upon exposure of the cells to 12-0-tetradecanoylphorbol-13 acetate. This down-regulation was prevented by preincubating the cells with sphingosine, a reported protein kinase C inhibitor. Two other protein kinase C inhibitors, palmitoylcarnitine and phloretin, were ineffective in preventing down-regulation by the phorbol ester. PMID- 3348801 TI - Enkephalin precursor gene expression in postmeiotic germ cells. AB - Preproenkephalin mRNA was detected in rat testis after postnatal day 30. A high abundance of preproenkephalin mRNA was present in the spermatids (i.e., spermatogenic cells at postmeiotic stage) purified from mature rat testis. The mRNA size of the spermatids was about 1900 bases, which was larger than that of other tissues expressing the preproenkephalin gene. The spermatids contained small amounts of enkephalin-containing proteins, but little or no Met-enkephalin. Preproenkephalin gene expression in the germ cells suggests the connection between gametogenesis and nervous system. PMID- 3348800 TI - Isolation of two neuropeptides in the AKH/RPCH-family from horseflies (Diptera). AB - Two neuropeptides (DCCI and DCCII) in the adipokinetic/red pigment concentrating hormone-family have been isolated and purified from the corpora cardiaca of horseflies (Diptera : Tabanidae). Both peptides were purified by a sequence of three reversed phase-high performance liquid chromatographic steps. Amino acid analysis of the purified peptides indicated the following composition for DCCI: Glx(l), Gly(1), Leu(1), Phe(1), Pro(1), Thr(2) and for DCCII: Glx(1), Gly(2), Leu(1), Phe(1), Pro(1), Thr(2), and Tyr(1). Photodiode array ultraviolet spectroscopy indicated the presence of tryptophan in both DCCI and II. Both DCCI and II had red pigment concentrating hormone activity in the crab, Uca pugilator. PMID- 3348802 TI - Interactions of adriamycin with a calcium binding site. AB - Terbium (Tb3+) luminescence has been used to investigate the interactions of adriamycin with a specific calcium binding protein, in the plasma membrane of GH3/B6 pituitary tumor cells. The luminescence intensity and lifetime of the Tb3+ GH3/B6 complex was quenched in the presence of adriamycin. According to Stern Volmer analysis, the quenching of Tb3+-GH3/B6 luminescence was by both membrane bound adriamycin (Ka = 3.7 x 10(5) M-1) and free adriamycin (kq = 7.3 x 10(7) M-1 s-1). The data suggests that, the calcium binding site at the outer surface of the membrane is collisionally accessible to freely diffusing adriamycin; and, that the toxin receptor site is located near the bound metal ion. PMID- 3348803 TI - A method for fixation of elastin demonstrated by stress/strain characterization. AB - In the process of examining the effects of oxidants on the mechanical properties of purified ligamentum nuchae elastin, it was found that sodium hypochlorite as constituted in Clorox will fix elastin at any preset extension. The treatments were carried out at a 1 to 5 dilution and at 0, 20 and 40% extensions. In each case, the new resting length was near the preset length and the elastic modulus increased remarkably, for example, from 1 to 5 x 10(7) dynes/cm2 for the sample preset at 20% extension. As reflected in the increased elastic modulus, the fixation was achieved by the formation of irreversible cross-links. Due to the near absence of side chains containing chemically reactive groups suitable for contributing to the formation of additional cross-links required in fixation, this is the first method whereby irreversible fixation of elastin has been achieved. The absence of a suitable fixative for elastic tissues such as lung, arteries, etc. has limited the microscopic characterization of functional extended states of these tissues. PMID- 3348804 TI - Buffers for the reconstitution of aspartate aminotransferase. AB - The cofactor activation of the apoenzyme of pig heart cytosolic aspartate aminotransferase was studied in various buffers. Cationic buffers are shown to allow maximal reconstitution in the pH range of 5.0 to 9.0. Anionic buffers made up of mono- and dicarboxylates are found to affect reconstitution in a pH dependent manner. At low pH, the carboxylates strongly inhibit reconstitution, but at high pH, they show less effect. In contrast, the more potent inhibitor Pi shows the opposite pH profile. Dicarboxylates are considerably more inhibitory than monocarboxylates. Substantial protection against inhibition by a number of carboxylates may be achieved by the addition of sodium chloride. PMID- 3348805 TI - Inactivation of bovine thrombin by water-soluble carbodiimides: the essential carboxyl group has a pKa of 5.51. AB - Bovine thrombin is rapidly and completely (greater than 99%) inactivated by 1 ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in a pseudo-first-order process. A plot of the pseudo-first-order rate constant for inactivation by 20 mM EDC at different pH values from pH 4.0 to 7.7 at 25 degrees C shows that inactivation is critically dependent on the protonated form of an acidic side chain with a pKa of 5.51. Significant protection against inactivation is provided by the competitive inhibitor dansyl-L-arginine N-(3-ethyl-1,5-pentanediyl)amide, suggesting that the essential carboxyl group may be involved in substrate binding. 1-Ethyl-3-(4-azonia-4,4-dimethylpentyl)carbodiimide (EAC) inactivates thrombin much more rapidly than EDC under the same conditions. PMID- 3348806 TI - Suppression of gastric ulcer induced by stress and HCL-ethanol by intravenously administered metallothionein-II. AB - A metallothionein isoform metallothionein-II was isolated from the livers of zinc acetate-treated rats. Metallothionein-II, which showed a single band on polyacrylamide gel electrophoresis, was subjected to two kinds of anti-ulcer screening systems. It was shown that intravenously administered metallothionein II suppressed the formation of rat water-immersion stress- and HCl-ethanol induced gastric ulcer significantly. The effect may partly be derived from the zinc contained in the metallothionein-II. However, the effect of metallothionein II was much stronger than that of an equivalent mole of zinc. Apparently, metallothionein-II had an anti-ulcerogenic activity not based on the effect of intrinsic zinc. PMID- 3348807 TI - Heme regulates cytochrome P-450 gene transcription elongation. AB - Administration of 3-methylcholanthrene (MC) to rats results in a striking increase in the transcription of cytochrome P-450 (c + d) messenger RNA with isolated nuclei, which is blocked by the simultaneous administration of cobalt chloride, an inhibitor of heme biosynthesis. Transcription of cytochrome P-450 (c + d) mRNAs with nuclei isolated from MC treated rats shows a linear increase with time of incubation, whereas it shows a progressive decrease with incubation time in the case of nuclei isolated from MC+CoCl2 treated rats. Addition of heme in vitro (10(-6)M) to the latter nuclei results in a significant counteraction of the decreased cytochrome P-450 (c + d) mRNA transcription. The inhibition in transcription rates observed in MC+CoCl2 treated rat liver nuclei is more pronounced with the seventh exon probe than with the second exon probe. Once again, in vitro heme addition can counteract the inhibition observed with both the probes. Since run off transcription with isolated nuclei represents essentially elongation of the initiated transcripts, the data obtained can be interpreted on the basis that heme regulates cytochrome P-450 gene transcription elongation. PMID- 3348809 TI - Cloning of cDNA encoding human H-protein, a constituent of the glycine cleavage system. AB - A cDNA that encodes human H-protein, a constituent protein of the glycine cleavage system, was cloned with anti-rat H-protein antibody as a probe from a human liver cDNA library constructed with an expression vector, lambda gt11. The longest size of cDNA of the isolated clones was about 750 base long (lambda HH15B9). On the other hand, we determined the primary structure of human H protein from the amino terminal Ser by the 12th Val, including a hexapeptide, Glu-Lys-His-Glu-Trp-Val-. In addition to the finding that most cDNA inserts cloned hybridized with the synthetic DNA probe composed of the possible sequences for the hexapeptide, we confirmed that lambda HH15B9 encodes the partial primary structure of H-protein in an open reading frame. PMID- 3348808 TI - Binding of C3 molecules to membranes via the SH-residue generated by the cleavage of a thioester bond can initiate complement activation. AB - Dithiopyridine (DTP)-dipalmitoylphosphatidylethanolamine (DTP-DPPE) was incorporated into liposome membranes to prepare DTP-liposomes. The DTP-liposomes could be lysed by reaction with the alternative complement pathway of any kind of serum tested. Activation of the alternative complement pathway has been shown to be mediated by the binding of C3 molecules to DTP on the liposomes via the SH residue generated by the cleavage of thioester bond in the alpha-chain of the molecules. PMID- 3348810 TI - Tight binding of glucocorticoid-receptor complexes to histone-agarose. AB - "Activated" glucocorticoid-receptor complexes purified about 3,000-fold from rat liver were found to bind to histone-agarose. Because of their tight binding, they could not be eluted from the column by high salt solution (3 M KCl) or low salt plus polyol buffer (50% ethylene glycol), but their binding could be disrupted by pyridoxal 5'-phosphate; more than 70% recovery of the "activated" receptor complexes was achieved with buffer containing 20 mM pyridoxal 5'-phosphate. This interaction of "activated" glucocorticoid-receptor complexes of rat liver with histone-agarose suggests a role of histones in the mechanism of action of steroid hormone. PMID- 3348811 TI - Short-term regulation of carnitine palmitoyltransferase activity in isolated rat hepatocytes. AB - An assay procedure for carnitine palmitoyltransferase is described which allows rapid measurement of the overt activity of this enzyme in isolated rat hepatocytes. In a one-step procedure digitonin permeabilizes the plasma membrane and at the same time carnitine palmitoyltransferase activity is measured. The use of the present procedure shows that carnitine palmitoyltransferase activity is regulated on the short term by different types of agonists. Thus, insulin, epidermal growth factor, vasopressin and the phorbol ester PMA inhibit carnitine palmitoyltransferase activity, whereas glucagon treatment renders the enzyme more active. These changes in enzyme activity coincide with corresponding changes in the rate of fatty acid oxidation. PMID- 3348812 TI - Chemotactic factor induced tyrosine phosphorylation of membrane associated proteins in rabbit peritoneal neutrophils. AB - Protein tyrosine phosphorylation in rabbit peritoneal neutrophils was examined by immunoblotting with antibodies specific for phosphotyrosine. Two tyrosine phosphorylated proteins were found with apparent molecular weights of 62,000 (p62) and 125,000. Both were enriched in the membrane fraction. Stimulation of the neutrophils with chemotactic factor fMet-Leu-Phe (10(-8)M, 20 sec) but not phorbol 12-myristate-13-acetate (0.1 microgram/ml, 10 min) caused rapid increase in tyrosine phosphorylation. The effect of fMet-Leu-Phe was inhibited by the pretreatment of neutrophils with pertussis toxin. The p62 protein was also recognized by antibody raised against a synthetic fragment commonly found in the tyrosine kinases of the src gene family. The results indicate that stimulation of the tyrosine phosphorylation of membrane associated proteins is one of the early events occurring in activated neutrophil and this stimulation of tyrosine phosphorylation may be regulated by a GTP-binding protein. PMID- 3348813 TI - Cathepsin L--a latent proteinase in guinea pig sperm. AB - Guinea pig spermatozoa were found to contain a fully-latent cysteine proteinase that could be unmasked by incubating epididymal sperm for 2 hr at pH 3.5 and 37 degrees C. The proteinase was identified as cathepsin L (EC 3.4.22.15) on the basis of its optimal hydrolysis of benzyloxycarbonyl-Phe-Arg-7-(4 methyl)coumarylamide (Z-Phe-Arg-NMec) at pH 5.5; lack of action on Z-Arg-Arg-NMec and Arg-NMec; urea-enhanced digestion of azocasein; marked sensitivity to thiol reagents, leupeptin, Z-Phe-Phe-CHN2, and L-trans-epoxy-succinylleucylamido(3 methyl)butane (Ep-475 or E-64-c); and insensitivity to pepstatin and serine proteinase inhibitors. Gossypol, a male antifertility agent, was inhibitory. The unmasking phenomenon was reversibly inhibited by HgCl2 and mersalyl acid, and prevented by leupeptin and Ep-475, but not by pepstatin. PMID- 3348814 TI - Intracellular calcium rise produced by platelet-activating factor is deactivated by fMet-Leu-Phe and this requires uninterrupted activation sequence: role of protein kinase C. AB - Stimulation of the neutrophils with fMet-Leu-Phe inhibits the rise in intracellular concentration of free calcium produced by the subsequent addition of platelet-activating factor. This deactivation is not observed in pertussis toxin treated cells. In addition, preincubation of the cells with the protein kinase C activator phorbol 12-myristate 13-acetate for three minutes abolishes completely the rise in calcium produced by platelet-activating factor. This inhibition is prevented by the addition of the protein kinase C inhibitor 1-(5 isoquinoline-sulfonyl)-2-methyl piperazine prior to the addition of the phorbol ester. Phorbol 12-myristate 13-acetate, at a concentration that does not produce significant inhibition, accelerates the rate of calcium removal from the cytoplasm, and this is abolished by the protein kinase C inhibitor. In contrast, the deactivation by fMet-Leu-Phe is not prevented by the protein kinase C inhibitor. The results presented here suggest that the protein kinase C system may regulate the opening by platelet-activating factor of possible plasma membrane associated pertussis toxin independent calcium channels and/or the binding of platelet-activating factor to the receptors. In addition, protein kinase C activation increases the rates of the calcium efflux pump and/or calcium sequestering by intracellular organelles. The most simple and straightforward explanation of the observed deactivation by fMet-Leu-Phe is that the addition of fMet-Leu-Phe to neutrophils stimulates the production of platelet-activating factor which then binds to and deactivates the receptors. PMID- 3348816 TI - Induction of a latency period in the time-course of phospholipase A2 action on dipalmitoylphosphatidylcholine liposomes in the gel phase. AB - The hydrolysis of dipalmitoylphosphatidylcholine liposomes by porcine pancreatic phospholipase A2 was studied at 31 degrees C, i.e., with the substrate in the gel phase. Addition of delipidated bovine serum albumin to the assay medium induces the appearance of a latency phase in the time course of the enzymatic action. The lag period can be abolished by addition of free palmitic acid whereas no reversal by lysolecithin is found. The generation of a latency period by albumin appears to be due to its ability to sequester the palmitic acid newly released by the phospholipase A2 catalysis. Thus, the nascent fatty acid seems to be an essential activator of the enzymatic process. PMID- 3348815 TI - Effect of endotoxin on the rat colon glutathione level. AB - The effect of endotoxin on the colon glutathione level was studied in male rats. Endotoxin (Escherichia coli) from 25 ug to 100 ug/100g body weight was administered intravenously. The Glutathione level was measured 16 hours after endotoxin was given. Results showed that endotoxin significantly enhanced the colon glutathione concentration as measured by 5,5'-dithiobis (2-nitrobenzoic acid). The increase which ranged from 11% to 50% was dose dependent. At an endotoxin dose of 1000 ug/100g body weight, colon glutathione level was found to be enhanced from 2 hours up to 48 hours. In contrast, the duodenum and jejunum glutathione levels were found to be significantly reduced. The increase in the colon glutathione level may have a protective effect against oxidative damage to the colon. PMID- 3348818 TI - Mitochondrial urea cycle enzymes in rats treated with sodium benzoate. AB - Since sodium benzoate, which is widely used to treat hyperammonemia its effect on mitochondrial urea cycle enzymes was investigated. its effect on mitochondrial urea cycle enzymes was investigated. Sodium benzoate was administered to urease treated hyperammonemic rats and controls. In both groups no interference with the activity of carbamylphosphate synthetase, ornithine carbamyltransferase and N acetylglutamate synthetase in the liver could be observed at concentrations of benzoate in plasma found in hyperammonemic patients. Careful monitoring of plasma levels reduces benzoate toxicity as shown in a patient with argininosuccinic aciduria. PMID- 3348817 TI - 31P-MRS study of bio-energy recovering phenomenon. AB - The ATP and creatine phosphate (PCr) contents in isolated guinea-pig hearts were determined by 31P-MRS measurement at 80.75 MHz using the Langendorff technique. Reperfusion of post-ischemic hearts with adenosine for 180 minutes increased ATP to 117.4% and decreased PCr to 59.8% of the preischemic value. Reperfusion without adenosine did not increase ATP and did not decrease PCr. The depressed cardiac function due to ischemia was remarkably improved in post-ischemic hearts by the increase in ATP due to adenosine. We found that the loss of ATP due to ischemia is not necessarily proportional to the extent of myocardial ischemic injury. PMID- 3348819 TI - Some characteristics of cyclic photophosphorylation in maize bundle sheath chloroplasts. AB - PMS-dependent photophosphorylation in bundle sheath chloroplasts isolated from Zea mays was monitored by using a continuous method. Carbonyl cyanide p trifluoromethoxyphenylhydrazone (FCCP) and venturicidin were shown to inhibit the ATP-synthesis. Venturicidin has been shown to inhibit ATP-formation in both mesophyll and bundle sheath chloroplasts. In contrast to the case in mesophyll chloroplasts, FMN was not able to promote photophosphorylation in bundle sheath chloroplasts. The effects of other cofactors and inhibitors on the ATP-synthesis in bundle sheath chloroplasts are shown. No photoinduced synthesis of inorganic pyrophosphate was seen, neither in bundle sheath chloroplasts, nor in mesophyll chloroplasts. PMID- 3348820 TI - Dopaminergic reduction of intracellular calcium: the role of calcium influx. AB - The effects of dopamine (DA) on 45Ca2+ ion movement and prolactin release in dispersed female rat anterior pituitary cells were studied to elucidate the mechanism for DA reduction of intracellular calcium levels. In 45Ca2+ prelabeled cells, DA inhibited fractional calcium efflux and prolactin release simultaneously and continuously in a concentration-dependent manner (IC50 20 nM DA). We then studied unidirectional calcium influx and observed haloperidol reversible, concentration-dependent DA suppression of calcium influx into unlabeled cells. These data complement and extend reported fluorescent dye studies and suggest that dopamine primarily inhibits calcium influx, thereby reducing intracellular calcium levels, which leads to suppression of prolactin release and is manifest secondarily as a reduction in fractional 45Ca2+ efflux. PMID- 3348821 TI - Identification of brain lesions in neuropsychiatric systemic lupus erythematosus by magnetic resonance scanning. AB - Cranial magnetic resonance imaging in 28 systemic lupus erythematosus patients who had experienced 30 acute neuropsychiatric events showed focal brain lesions in 16 of 30 events (53%) and low brain volume (atrophy) in 20 of 30 events (67%). Definite focal lesions were significantly more frequent in patients with clinically localized neurologic deficits (8 of 8, 100%), or seizures (5 of 6, 83%) than in patients without such localizing signs (3 of 16, 19%). Many of these lesions were occult on intravenous contrast-enhanced x-ray computed tomography. In 2 patients, lesions in gray matter resolved within 2 or 3 weeks, in association with clinical improvement. Magnetic resonance imaging is an important technique for detecting the extent of brain injury in cerebral lupus. PMID- 3348822 TI - The terminal complement complex, C5b-9, a marker of disease activity in patients with systemic lupus erythematosus. AB - Concentrations of the terminal complement complex (TCC), C5b-9, were examined in 120 serum samples from 28 patients with systemic lupus erythematosus. Eleven patients with various manifestations of the disease were followed longitudinally for a 2-year period during active and inactive phases of the disease. In 9 of the 11 patients, elevations in TCC concentrations correlated with disease exacerbations. In many of these patients, C3 and C4 levels remained normal during the study and were less sensitive indicators of disease activity than were TCC concentrations. We believe that measurements of TCC are useful in monitoring patients with rheumatic diseases in which complement activation is a component. PMID- 3348824 TI - Radiographic assessment and psychologic variables as predictors of pain and functional impairment in osteoarthritis of the knee or hip. AB - Sixty-five outpatients with osteoarthritis of the knee and/or hip were assessed using radiographic ratings of disease severity, measures of psychologic coping, and multidimensional clinical outcomes of degree of pain and functional impairment. Disease severity accounted for little of the individual variability in clinical outcomes. Even after controlling for disease severity, psychologic variables remained strong predictors of individual differences in functional impairment and pain. Psychologic processes deserve greater clinical and research attention as potential mediators between disease severity and clinical outcome. PMID- 3348823 TI - Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. AB - Of 397 systemic sclerosis (scleroderma) patients from the University of Pittsburgh, who had serum determinations of both anti-Scl-70 and anticentromere antibody (ACA), 26% had anti-Scl-70 and 22% had ACA. No patient had both autoantibodies. Weak associations with HLA-DR5 and HLA-DR1 were detected with anti-Scl-70 and ACA, respectively. ACA was found almost exclusively (96%) in patients with limited cutaneous scleroderma (the CREST syndrome variant), but the majority (57%) of patients with limited scleroderma did not have this antibody. Among patients with limited scleroderma, those with ACA more often had calcinosis and telangiectasias and less often had pulmonary interstitial fibrosis and restrictive lung disease. However, the frequency of pulmonary hypertension and the survival rates were similar in the ACA+ and ACA- limited scleroderma patients. Two-thirds of patients with anti-Scl-70 had diffuse scleroderma, but only 33% of all diffuse scleroderma patients had this antibody. Within the subset of diffuse scleroderma, anti-Scl-70 was associated with peripheral vascular disease (digital pitting scars) and pulmonary interstitial fibrosis, but was not predictive of cardiac or renal involvement or survival. ACA and anti-Scl-70 are useful in diagnosing and classifying systemic sclerosis variants and in predicting the natural course of the disease. Their mutually exclusive occurrence suggests either 2 separate clinical entities or important host factors determining their production. PMID- 3348825 TI - Anti-Ro (SS-A) antibodies from Ro (SS-A)-immunized mice. AB - Immunization of BALB/c mice with immunoaffinity-purified bovine or human Ro (SS A) induces the production of antibodies reactive with Ro (SS-A). Fusion of spleen cells from the hyperimmunized mice to SP2/0 cells resulted in hybridoma cell lines that produced anti-Ro (SS-A) antibodies. Anti-Ro (SS-A) binding was established by solid-phase immunosorbent assay, immunoblotting, or RNA immunoprecipitation. Most of the anti-Ro (SS-A) antibodies bound to both human and bovine Ro (SS-A) in the solid phase, but only one of the monoclonal antibodies selectively bound to human Ro (SS-A); this suggests that there are species differences between the bovine and human Ro (SS-A) antigens. Indirect immunofluorescence studies demonstrated that most anti-Ro (SS-A) antibodies bound to cytoplasmic or nuclear HEp-2 cellular antigens, whereas others did not bind to fixed HEp-2 tissue culture cells. Nuclear staining of mouse substrates by one of the sera containing anti-Ro (SS-A) demonstrated that autoantibodies were induced by immunization with human Ro (SS-A). PMID- 3348826 TI - Articular responses to purified cartilage proteoglycans. AB - To examine whether proteoglycans (PGs) liberated from cartilage might contribute to articular changes in arthritis, cartilage PGs were injected intraarticularly into rabbit knee joints. Twice-weekly injections of PG (2.5 mg) provoked synovial hypertrophy, synovitis, erosion of the articulating surfaces, and loss of metachromasia of the articular cartilage. These changes were accompanied by a marked elevation in the production of neutral collagenase and gelatinase by both synoviocytes and chondrocytes. The synoviocytes of experimental knee joints also produced factor(s), possibly related to interleukin-1, which provoked the activation of chondrocytes. Our data are consistent with the idea that free PG fragments mediate some of the pathophysiologic changes that occur in arthritic joints. This property may be particularly important in osteoarthritis. PMID- 3348827 TI - Stability of normal joint findings in persistent classic rheumatoid arthritis. AB - We reviewed the records of 44 patients, retrospectively selected because they had had persistently active rheumatoid arthritis for more than 5 years (mean +/- SD followup 9.8 +/- 2.6 years) and because they met the American Rheumatism Association criteria for classic disease, to determine the change in extent of the anatomic distribution of joint involvement over time. The positive predictive value of a lack of inflammation in a joint during the first year for the lack of involvement over the ensuing 4 years was 87%. Thirty-eight of the 43 joints that required replacement were inflamed in the first year of disease. PMID- 3348828 TI - Acquired immunodeficiency syndrome mimicking Sjogren's syndrome and systemic lupus erythematosus. AB - We describe a patient in whom the diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was delayed because her clinical symptoms were similar to those of systemic lupus erythematosus and Sjogren's syndrome and because of a false-negative result on a Western blot test for human immunodeficiency virus. The importance of using different diagnostic tests for AIDS and the pitfalls in diagnosing AIDS in patients who appear to have connective tissue disease are discussed. PMID- 3348829 TI - Synovial complications of spondylepiphyseal dysplasia of late onset. AB - We describe 2 patients with a late-onset type of spondylepiphyseal dysplasia who developed multiple synovial complications. The synovial manifestations in the first patient included recurrent episodes of acute arthritis due to calcium pyrophosphate dihydrate crystal deposition and, later, chronic synovitis with radiologically evident chondrocalcinosis. In the second patient, cholesterol crystals in synovial fluid, multiple osteochondromata, and a histologic appearance resembling pigmented villonodular synovitis on synovial biopsy were seen. Osteochondromata were identified in 4 other members of this patient's family. Synovial manifestations in the osteochondrodysplasias may be more common than previously recognized. PMID- 3348830 TI - On the treatment of rheumatoid arthritis with M&Ms (Motrin & methotrexate) PMID- 3348831 TI - Immune thrombocytopenia in association with oral gold treatment. PMID- 3348832 TI - Wegener's granulomatosis with acute pericardial tamponade. PMID- 3348834 TI - The use of magnetic resonance imaging (MRI) in patients with rheumatoid arthritis and subluxations of the cervical spine. PMID- 3348833 TI - Episodic polyarthralgia associated with Hashimoto's thyroiditis. PMID- 3348835 TI - Homocysteine content of plasma proteins in ischemic heart disease. AB - It has been shown previously that accumulation of homocysteine produces atheromatous changes. The present study was done on 26 male survivors of myocardial infarction 2-3 months after the acute phase and 26 healthy males of the same age (30-60 years). The concentrations of homocysteine, its derivatives and other amino acids were determined in acid hydrolyzate of plasma and in deproteinized plasma. The plasma proteins of survivors of myocardial infarction were found to contain a high concentration of homocysteine. The average value was 958 +/- 84 mumol/l of plasma, which was about 25 times the quantity found in the control group. Large differences were also found in alpha-amino adipic acid and cystathionine concentrations. These substances were found in significantly higher concentrations in the plasma of the survivors compared to controls. The high positive correlation between homocysteine and alpha-amino adipic acid level (r = 0.83; P less than 0.001) suggests a common source of these 2 compounds in the analyzed samples. The levels of the other 15 measured amino acids were not significantly different in the 2 groups. The results support the homocysteine theory and suggest a method for more exact diagnosis of atherosclerosis. PMID- 3348836 TI - Inhibitory effect of calcium antagonists on balloon catheter-induced arterial smooth muscle cell proliferation and lesion size. AB - Calcium antagonists inhibit atherogenesis in the cholesterol-fed rabbit without producing hypolipidaemia, suggesting a direct action on the arterial wall. In this study, the effects of several calcium antagonists on the myoproliferative response to balloon catheter injury of the aorta have been investigated in normolipidaemic rats and rabbits. The incorporation of [3H]thymidine into rat aortic DNA 48 h after balloon injury was markedly reduced by twice daily oral administration of nifedipine, verapamil, diltiazem or lanthanum. DNA synthesis in other proliferating tissues was unaffected. Twice daily oral administration of prazosin or minoxidil, antihypertensive agents that are not calcium antagonists, also selectively reduced arterial DNA synthesis. In balloon catheterised rabbits twice daily oral administration of nifedipine (10 mg/kg) caused a 39% reduction in the cross-sectional area of the neo-intima 14 days after injury. These results show that nifedipine and other antihypertensive agents inhibit smooth muscle cell proliferation. PMID- 3348837 TI - The relationship of high density lipoprotein subfractions to alcohol consumption, other lifestyle factors, and coronary heart disease. AB - Serum high density lipoprotein (HDL) levels are inversely related to the risk of coronary heart disease. Controversy exists regarding the relative importance of HDL subfractions, and few studies have related subfraction levels to lifestyle factors associated with coronary risk. We examined the relationship of the major subfractions, HDL2 and HDL3, to alcohol consumption, cigarette smoking, physical exercise, body mass index, and socioeconomic status in 88 men and 49 women aged 35-64 years. Body mass index was inversely related to HDL2-cholesterol (C), particularly in men, but had no significant relationship with HDL3-C. Cigarette smoking and degree of physical exercise were not significantly related to either HDL subfraction. Alcohol consumption had a strong positive correlation with HDL3 C in both sexes; this association was statistically significant after controlling for cigarette smoking, body mass index, and serum triglyceride. Minnesota-coded ECG abnormalities and positive responses to the WHO chest pain questionnaire were associated with lower levels of HDL-C and HDL2-C in both sexes, and significantly lowered levels of HDL3-C in men but not women. These findings suggest that HDL3 C, as well as HDL2-C, may be related to coronary risk, and indicate that the protective effects of alcohol consumption may be mediated via this subfraction. PMID- 3348838 TI - Antiatherosclerotic and antihyperlipidemic effects of octimibate sodium in rabbits. AB - Octimibate sodium (8-[(1,4,5-triphenyl-1H-imidazol-2-yl)oxy]octanoic acid, sodium salt; NAT 04-152) was investigated for its antihyperlipidemic and antiatherosclerotic activities in New Zealand White rabbits. Hypercholesterolemia and atherosclerosis were induced by feeding a diet containing 0.3% cholesterol for 8 weeks. In addition, repeated injections of bovine serum albumin (BSA) were used to enhance the experimental atherosclerosis. Octimibate sodium, 10.0 and 30.0 mg/kg p.o., reduced both the increase in serum cholesterol levels and the aortic plaque-formation (by about 50% in the higher dose group) as compared to control animals. Serum triglyceride levels were not influenced. Biochemical and histological examinations of the aortas showed reduced cholesterol contents in the higher dose group and a dose-dependent inhibition of pathological changes in the aortas. PMID- 3348839 TI - Proliferation and LDL binding of cultured intimal smooth muscle cells from rabbits. AB - Cultured intimal smooth muscle cells (SMC) were prepared from rabbits in which a cannula had been inserted into the abdominal aorta 4 weeks previously. The patterns of growth proliferative rates, and lipoprotein metabolism of cultures of intimal and medial SMC from intact aortic media were compared. Intimal SMC proliferated more rapidly than medial SMC. Both low density lipoprotein (LDL) and acetylated LDL bound to intimal SMC, whereas only LDL bound to medial SMC. These findings suggest a phenotypic difference between intimal and medial SMC. PMID- 3348840 TI - Modified plasma-derived lipoproteins in human atherosclerotic plaques. AB - Low density lipoproteins extracted from surgical specimens of human atherosclerotic plaques (A-LDL) showed altered electrophoretic mobility indicating a greater negative charge than that of plasma LDL (P-LDL). A-LDL but not P-LDL showed high affinity binding/degradation by human monocyte-derived macrophages; this was inhibited by acetylated LDL but not by native P-LDL. Following injection of 125I-labelled autologous P-LDL prior to reconstructive arterial surgery, polyacrylamide and agarose gel electrophoresis of A-LDL extracted from arterial intima showed that the A-LDL and its apolipoprotein B moiety were derived from P-LDL; the electrophoretic mobility of the product A-LDL was greater than that of native P-LDL. The compositions of arterial intermediate density lipoprotein (A-IDL) and A-LDL differed from those obtained from human plasma intermediate density lipoprotein (P-IDL) and P-LDL. A-IDL showed a reduced triglyceride content and increased esterified and unesterified cholesterol. Although the total cholesterol content of A-LDL was similar to that of P-LDL, there was an increase in unesterified cholesterol and a decrease of cholesteryl ester. These studies indicate that LDL extracted from human atherosclerotic plaque is derived from and modified from P-LDL in vivo. Compared with native P LDL, A-LDL showed differences in charge and composition, associated with its high affinity binding by the acetyl LDL receptor of human macrophages. PMID- 3348841 TI - Atherogenesis in two strains of obese rats. The fatty Zucker and LA/N-corpulent. AB - Two strains of obese rats, the fatty Zucker and the LA/N-corpulent have been compared at 6 months age for the presence of vascular and myocardial disease. Both strains, when obese, exhibit a VLDL hyperlipidemia with elevated triglycerides and moderate elevations of plasma cholesterol concentrations compared to the lean rats of the same strain. The hyperlipidemia is more modest in the fatty Zucker than the corpulent LA/N, and the serum lipid concentrations of the lean Zucker are lower than those of the lean LA/N. Apolipoprotein concentrations were similar and elevated in the two obese genotypes compared to the lean genotypes which were also similar to each other. Male and female obese animals of both strains exhibited hyperinsulinemia under fasting conditions and after oral glucose, with obese male LA/N rats exhibiting the most severe hyperinsulinemia. Glucose tolerance was impaired in obese LA/N animals but was normal in lean rats of both strains and fatty Zucker rats of both sexes. The glucose intolerance observed in obese LA/N animals was more severe in the male than in the female rats. Unlike the corpulent rat, which develops atherosclerotic lesions, the fatty Zucker shows no evidence of advanced vascular lesions on scanning electron microscopy. The fatty Zucker also does not develop the myocardial lesions that are frequent in the male corpulent LA/N rat. It is suggested that the initiation of the atherogenic process is dependent upon elevated insulin levels or transient hyperglycemia. Development of the advanced lesions appears to require the presence of hyperlipidemia. PMID- 3348842 TI - Atherogenic risk in men suffering from occupational stress. AB - Blue-collar workers suffering from chronic occupational stress exhibit significantly higher values of an atherogenic index (ratio between low density and high density lipoprotein cholesterol assessed by quantitative lipoprotein electrophoresis) as compared to men exposed to less stress at work. Chronic occupational stress is defined by interactions of objective (job instability, shift work) and subjective (perceived job insecurity, perceived increase of work load) indicators as assessed by structured interviews. Findings from a prospective epidemiologic study on 416 middle-aged men at entry covering a 2-year period of observation hold true after controlling for several confounding factors such as body weight, age, cigarette smoking and chronic alcohol consumption. Results are in line with experimental animal studies on the influence of chronic social stress on the development of atherosclerosis. PMID- 3348843 TI - Influence of etofibrate on low density lipoprotein metabolism. AB - This study examined the effect of single dose etofibrate (1.0 g/day) on plasma lipids and lipoproteins in a group of eleven hypercholesterolemic individuals. The drug lowered plasma triglyceride and cholesterol by 32% and 14%, respectively (P less than 0.005). The cholesterol reduction came from a decrement in both VLDL and LDL. The cholesterol content of HDL did not change although its mass as determined by analytical ultracentrifugation rose by 29%. LDL metabolism was followed before and during drug therapy. Treatment increased catabolism of this lipoprotein by 14%, without affecting synthesis. The increased clearance resulted from activation (64%) of the LDL receptor pathway. There was a reciprocal decrease in the amount of lipoprotein channelled into the receptor-independent route. PMID- 3348844 TI - Lipoprotein uptake in primary cell cultures of rabbit atherosclerotic lesions. A fluorescence microscopic and flow cytometric study. AB - To characterize the lipoprotein metabolism of lipid-filled cells of atherosclerotic lesions, uptake of 3,3'-dioctadecylindocarbocyanine (DiI) labelled low density lipoprotein (LDL), acetylated LDL (Ac-LDL) and beta-very low density lipoprotein (beta-VLDL) was studied by fluorescence microscopy and flow cytometry in primary cultures of enzymatically dispersed aortic cells from cholesterol-fed rabbits. Most of the foam cells were identified as macrophages on the basis of Fc-receptors and high activities of nonspecific esterase and acid lipase, although cholesteryl ester (CE) inclusions were found by filipin staining also in smooth muscle cells (SMCs). During the culture only SMCs proliferated and were confluent in about 1 week. After incubation with DiI-Ac-LDL most macrophage foam cells were brightly fluorescent, but also many SMCs accumulated fluorescence. In SMCs, an excess of LDL inhibited the uptake of DiI-beta-VLDL and DiI-LDL, indicating that these lipoproteins were taken up by the apoB,E receptor; the activity of this receptor was low 2 days after cell isolation but increased considerably during SMC proliferation. DiI-beta-VLDL was not taken up by the macrophage foam cells until after 7 days' culture, when their CE content had decreased, reflecting a feed-back regulation of these receptors as well. Our results indicate that, in primary cultures of enzyme-dispersed cells from rabbit atherosclerotic lesions, most of the foam cells have lipoprotein receptors resembling those described in macrophages and that also many SMCs accumulate Ac LDL. PMID- 3348845 TI - Effects of melatonin on genetic hypercholesterolemia in rats. AB - Administration of the pineal hormone melatonin to genetically hypercholesterolemic rats resulted in a decrease in plasma cholesterol levels and in an improvement of fatty changes of the liver. Thus, the antihyperlipemic effect of melatonin, which was first discovered in hypercholesterolemia produced by short- or long-term administration of glucocorticoids, has now been proved to be rather universal and not simply anti-glucocorticoidal. The mechanism of the decrease of plasma cholesterol levels remains unknown. It was also found that the pathogenesis of this so-called genetic hypercholesterolemia in rats involved biochemical nephrotic changes and histopathological changes in the kidney. PMID- 3348846 TI - A question concerning apo B-48. PMID- 3348848 TI - Standards of practice. PMID- 3348847 TI - Perspectives in occupational health nursing. PMID- 3348849 TI - Occupational health nursing: a commitment to excellence. PMID- 3348850 TI - Preparing grants. Developing the proposal. Part II. PMID- 3348852 TI - Glaucoma: questions & answers. PMID- 3348851 TI - Ophthalmic issues. Facts and myths: misconceptions about eye care. PMID- 3348854 TI - Prospective labor risk assessment in a rural community hospital. AB - This prospective study investigates the utility of a labor risk assessment instrument for the prediction and management of the low Apgar infant in the community hospital setting. Two hundred and fifty patients in labor were managed with a protocol involving initial and ongoing risk assessment throughout the course of labor and delivery. Patients scored as high risk were independently assessed to determine the need for the presence of the resuscitation team at delivery. Twenty-one percent of infants of high-risk mothers required resuscitation, whereas only 8% of infants whose mothers scored as low or moderate risk required resuscitation. A modified ten factor list was developed using multiple logistic regression analysis and clinical experience. This was found to improve predictive power for low Apgar score infants in need of resuscitation within a risk group comprising only 27% of the population. We conclude that this intrapartum scoring system can be readily implemented in a community hospital and is effective in identifying high-risk infants so that resources can be mobilized for appropriate intervention. PMID- 3348853 TI - Influence of young maternal age and parity on term and preterm low birthweight. AB - Data on 4496 singleton births to young women (19 years or less) are reported by maternal age and parity with birthweight and gestation cross-classified to yield rates of preterm and term low birthweight. After adjustment, the risk of preterm low birthweight was increased with very young maternity (15 years or less); preterm low birthweight and term low birthweight were each increased with young multiparity. These data suggest that the identification of factors associated with preterm birth and their incorporation into the prenatal care regimen may be important in improving pregnancy outcome in young women. PMID- 3348855 TI - Catechol-o-methyl transferase activity in the human term placenta. AB - Catechol-O-methyltransferase (COMT) characteristics and activity were studied using radioenzymatic techniques in placentas from normal and high-risk patients at term. The affinity of the catechol estrogen 20-hydroxyestrone (2OHE1), Km = 5 microM, for the enzyme was found to be at least 90-fold higher than that of the catecholamines norepinephrine, epinephrine, and dopamine (450, 490, and 850 microM, respectively). The product formed after incubation of placental cytosol with tritiated 20HE1 was identified as being exclusively (3H) 2-methoxyestrone, by use of high-performance liquid chromatography. Placental COMT activity after normal spontaneous delivery was no different from that obtained after elective cesarean section (270 +/- 20 versus 275 +/- 27, expressed as mean +/- SE activity nanomoles of 2-methoxyestrone formed per hour/mg protein). Placental COMT activity at term in women with hypertension (toxemia [T] or chronic hypertension [CHBP]) was significantly lower than in control subjects (284 +/- 27 versus 183 +/- 26; P less than 0.05). No significant differences in enzyme activity were found between T and CHBP (175 +/- 37 versus 210 +/- 32, P = NS). There were also no differences in COMT activity of diabetic classes A-R (White classification), fetal distress (with or without acidosis), and controls. The possible interference of antihypertensive drugs used by the patients in the study on COMT activity was assessed. Incubations of healthy placental cytosol with hydralazine, methyldopa, and Mg++ in their estimated plasma therapeutic concentrations had no effect on placental COMT activity. The present study suggests that placental COMT activity is low in patients with hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3348856 TI - Use of verapamil for paroxysmal supraventricular tachycardia during epidural anesthesia for cesarean section. PMID- 3348857 TI - Gastrointestinal perforations in the neonatal period. AB - Forty-eight neonates were treated for gastrointestinal perforation during a 9 year period. In 30, perforation occurred within the first week of life. Thirty six were preterm infants and many had a history of obstetric and postnatal complications. Perforation resulted from necrotizing enterocolitis in 26 patients, whereas in 14 neonates spontaneous perforation occurred in an apparently normal bowel, with no evident cause (idiopathic perforation). In 6 patients perforation was associated with meconium ileus. Primary closure was carried out for perforations of the duodenum and stomach. Intestinal perforations were usually treated by resection and enterostomies. The overall mortality rate in this series was 46%. The highest mortality rate was associated with necrotizing enterocolitis (62%). The mortality rate was only 14% in patients with idiopathic perforation. Despite improvement in the prognosis of neonatal gastrointestinal perforations in recent years, it is still discouraging, reflecting the difficulty in preventing and treating necrotizing enterocolitis. PMID- 3348858 TI - An assessment of the first decade's experience with antepartum fetal heart rate testing. AB - The utility of antepartum fetal heart rate (APFHR) monitoring (nonstress test and the contraction stress test) was evaluated for a 10-year interval from 1974 through 1983. The number of high-risk patients evaluated increased from 2.9 to 25.1% of all deliveries. The decade's perinatal mortality rate differed from 22.4 per 1000 in the nontested population to 11.8 per 1000 in the tested population; the stillbirth rate differed from 11.1 per 1000 to 5.4 per 1000 uncorrected, 2.2 per 1000 corrected, and perinatal morbidity also differed from 26.1 per 1000 to 24.9 per 1000 (NS). Improvement statistics appear to plateau by the fourth year. An abnormal APFHR test was associated with a lethal congenital anomaly in 2.54% of patients (versus 0.5 to 1.5% in the general population). Evaluation for the presence of congenital anomalies appears to be indicated in the fetus with an abnormal APFHR test. A lower stillbirth rate occurred within 4 days of a normal APFHR test (0.027%) compared with a test interval of 5 to 7 days (0.11%). Thus, APFHR testing performed twice weekly may offer a better outcome for the fetus at risk than once weekly testing. This report confirms that the chief value of APFHR testing is its ability to identify the normal healthy fetus. These tests are somewhat less accurate at identification of the sick fetus. The nonstress test and contraction stress test were found to be of similar clinical predictive value. PMID- 3348859 TI - Rupture of intracranial aneurysm associated with cocaine use during pregnancy. PMID- 3348860 TI - Urinary C-peptide in the neonate correlates both to maternal glucose tolerance and to fetal size at birth. AB - In 18 women with gestational diabetes the variables of an oral glucose tolerance test (fasting and 2-hour blood glucose values and area under the blood glucose curve) performed in the last trimester of pregnancy correlated significantly with the urinary C-peptide excretion during the first 12 hours of the life (r = 0.47, 0.71, and 0.60, respectively). In a combined group with 28 type II pregnant diabetic women there was also a significant correlation between the urinary C peptide excretion of the infants and their skinfold. Assay of the urinary C peptide excretion of the neonate, reflecting its insulin production, seems to be a sensitive parameter to study the influence of the maternal carbohydrate metabolism in the offspring. PMID- 3348861 TI - Clinical significance of liver dysfunction in pregnancy-induced hypertension. AB - Hepatic dysfunction is one of the frequent manifestations of multisystemic involvement in preeclampsia. This study was conducted to establish the impact of liver dysfunction on maternal and neonatal outcome in women with pregnancy induced hypertension (PIH). The prevalence of liver dysfunction as determined by an elevated serum glutamic oxalacetic transaminase (SGOT) concentration was 21% in a population of 355 patients with PIH. Liver dysfunction was associated with the presence of severe hypertension, proteinuria, a lower platelet count, and renal compromise (elevated blood urea nitrogen, creatinine, and uric acid serum concentrations). Abdominal pain was also associated with an SGOT elevation. Liver dysfunction was associated with intrauterine growth retardation and prematurity. Furthermore, the association with these neonatal complications was independent from the severity of the hypertension and the presence of proteinuria. Thus, we conclude that liver dysfunction is a frequent complication of PIH and that it is an independent risk factor for maternal and perinatal complications. PMID- 3348862 TI - Effects of supine exercise on fetal heart rate in the second and third trimesters. AB - The effects of a brief period of supine exercise on fetal heart rate (FHR) was studied in 25 healthy, regularly exercising women, 12 in the late second trimester and 13 in the mid third trimester. Although statistically significant increases in maternal mean arterial pressure and pulse occurred, the exercise intensity was mild, with the average percent maximal pulse being 46 +/- 5% and 49 +/- 5% in the second and third trimester groups, respectively. Small increases in FHR were seen in both groups, which were insignificant statistically and physiologically. No patient experienced significant FHR abnormalities as a result of the supine exercise sequence. The findings suggest that pregnant women may continue submaximal supine exercise of short duration into the mid to late third trimester. PMID- 3348863 TI - Glucose tolerance, fetal growth, and pregnancy complications in normal women. AB - Currently, gestational diabetes is often defined by the criteria of O'Sullivan, with those patients not included as gestationally diabetic being considered normal. Recently, Tallarigo and coworkers reported that serum glucose variations within the normal range could affect the birthweight of the neonate and also could relate to the frequency of complications often associated with diabetes in pregnancy. This study confirms the correlation between the plasma glucose concentration at 2 hours on the 100 gm, 3-hour glucose tolerance test and birthweight. When women demonstrating 2-hour glucose values of 139 mg/dl or less are compared with those demonstrating values 140 mg/dl or greater, fetuses from the group with higher plasma glucose values had higher birthweights (+211 gm) and were more often macrosomic (24.4 versus 8.6%). We were unable to identify any relationship between these small variations of glucose tolerance and pregnancy complications, such as delivery by cesarean section, birth trauma, pregnancy induced hypertension, or congenital anomalies. PMID- 3348864 TI - Comparison of auditory brainstem responses and pneumograms in intensive care nursery infants. AB - Central slowing of auditory brainstem responses (ABRs) and excessive breathing irregularity on pneumogram recordings indicate dysfunction in central auditory pathways and brainstem respiratory control mechanisms, respectively. These centers are anatomically proximate within the brainstem so that ABR slowing and respiratory instability might be expected to occur concomitantly, reflecting overall dysfunction of this part of the central nervous system. To examine the relationship between these two assessments, testing results were compared for 15 infants in the intensive care nursery who had ABRs and 12-hour pneumograms performed at about the same age for separate clinical indications. Wave V latency at 70 dB was found to correlate significantly with three pneumogram measurements of breathing irregularity: the density of short apneas during sleep (p less than 0.01), the number of episodes of periodic breathing per 100 minutes of sleep (p less than 0.05), and the percentage of sleep time spent in periodic breathing (p less than 0.05). Interwave interval I-V correlated significantly with the density of short apneas during sleep (p less than 0.01). The auditory brainstem response and the pneumogram appeared to serve as related indicators of brainstem function in these infants. PMID- 3348865 TI - The effect of fetal hypoxia and acidosis on the changes in fetal electroencephalogram during labor. AB - As artefact-free recordings of the fetal brain bioelectric potentials can only be obtained by specially designed electrodes, an electrode for taking electroencephalogram (EEG) and cardiotocogram (CTG), according to the principle of vacuum electrode developed by Rosen and Scibetta, has been designed. The polygraphic technique was used to examine a total of 65 deliveries, divided into two groups. The first group (n = 33) consisted of newborns free of any signs of hypoxia and acidosis, whereas the second group (n = 32) was comprised of newborns with evident clinical and biochemical signs of hypoxia and acidosis. Fetal hypoxia and acidosis were observed to entail some characteristic changes in EEG, that is, a decrease in the frequency and wave amplitude through the appearance of the isoelectric line (ISO) featuring in severe cases of fetal hypoxia and acidosis. The following changes were found to occur during the development of hypoxia and acidosis:hypoxia, a decrease in the EEG frequency and amplitude, preacidosis with the appearance of both early and late decelerations coupled with a significant drop in the oscillation and, eventually, severe variable decelerations accompanied by terminal bradycardia. The time interval between the manifestation of initial signs of a decreasing central nervous system (CNS) activity and changes in the fetal heart rate was found to be about 10 minutes. PMID- 3348866 TI - Neonatal depression and birth asphyxia in the low birthweight neonate. PMID- 3348867 TI - Neonatal depression and birth asphyxia in the low birthweight neonate. AB - In 392 low birthweight neonates, acidosis as evident from umbilical artery pH 7.1 or less was strongly associated with Apgar score 6 or lower at 1 minute. However, most cases that were depressed (Apgar score 6 or lower at 1 minute) were not acidotic. Neonatal depression was most strongly and directly correlated with gestational age. Neonatal depression and birth asphyxia are distinct entities. PMID- 3348868 TI - New inhibitor(s) of 15-hydroxyprostaglandin dehydrogenase in human milk. AB - New inhibitor or inhibitors of nicotinamide-adenine dinucleotide-dependent 15 hydroxyprostaglandin dehydrogenase (PGDH) activity were found in breast milk but not in powdered milk. Milk samples were obtained manually from 23 puerperae who had delivered at 38 to 41 weeks. The inhibition pattern was competitive and noncompetitive. The percentage of inhibition of PGDH activity kept at 4.0 degrees C increased to a maximum at 12 hours after milk sampling and decreased thereafter. The percentage of inhibition of each milk sample decreased gradually with the duration postpartum. In addition, the inhibitor or inhibitors showed a smaller molecular weight than 1000 daltons and were partially resistant to heat and trypsin. Moreover, they were easily soluble in petroleum ether at various pH values, although the adsorption to C18 cartridge was inadequate. These new factor or factors may increase the benefits of breast feeding. PMID- 3348870 TI - Electronic fetal monitoring during premature labor and the occurrence of perinatal mortality in very low birthweight infants. PMID- 3348869 TI - Fetal heart rate tracing with congenital aneurysm of the great vein of Galen. AB - A fetal heart rate tracing that is notable for decreased short- and long-term variability is seen in association with normal umbilical cord blood gas values. A great vein of Galen aneurysm is diagnosed in the neonatal period. This case exemplifies a central nervous system disorder that is present before labor and is associated with normal oxygenation of the fetus and an abnormal fetal heart rate tracing. The causes of diminished fetal heart rate variability are discussed. PMID- 3348871 TI - The role of social support in the prevention of preterm birth. PMID- 3348872 TI - Commentary: rethinking social support in preterm birth prevention. PMID- 3348873 TI - Free-standing birth centers: prospects and problems. PMID- 3348874 TI - Recent trends in family-centered maternity care for cesarean-birth families. PMID- 3348875 TI - Commentary and response: the malpractice insurance crisis and free-standing birth centers. PMID- 3348876 TI - A quick reference table of interventions to assist families to cope with pregnancy loss or neonatal death. PMID- 3348877 TI - Newborn surgery without anesthesia: is the problem solved? PMID- 3348878 TI - How to raise professional awareness of the need for adequate pain relief for infants. PMID- 3348880 TI - Adult idiopathic thrombocytopenic purpura. PMID- 3348879 TI - Relationship of street drug use, hospitalization, and psychosocial factors to low birthweight among low-income women. PMID- 3348881 TI - Diabetes mellitus: a study utilizing the revised diagnostic criteria. PMID- 3348882 TI - Alcohol: your child and drugs. PMID- 3348883 TI - Terminating the doctor-patient relationship. PMID- 3348884 TI - Sweeteners: nutritive and non-nutritive. PMID- 3348885 TI - Human placental glutathione transferase: interactions with steroids. AB - Glutathione transferases exhibit both isomerase and transferase activity. The acceptance of steroids as substrates for or inhibitors of these activities was studied using a 350-fold enriched preparation of the enzyme from human placenta. As an isomerase, the enzyme preparation catalyzed the conversion of pregn-5-ene 3,20-dione (Km 0.03 mmol/l) and androst-5-ene-3,17-dione (Km 0.05 mmol/l) to the respective 4-ene-3-oxosteroids (specific activity 0.8 U/mg protein). This isomerase activity strictly depended on the presence of glutathione (Km 0.04 mmol/l). As a transferase, the enzyme preparation catalyzed the conjugation of glutathione (Km 0.5 mmol/l) with 1-chloro-2,4-dinitrobenzene (Km 1.0 mmol/l) (specific activity 100 U/mg protein). This transferase activity was inhibited by all phenolic (KI values 0.2-1.5 mmol/l) and some of the neutral steroids (KI values 1.4-3.5 mmol/l) tested. Phenolic steroids inhibited the enzyme activity competitively to 1-chloro-2,4-dinitrobenzene and non-competitively to both substrates. The results indicate that steroids can interact with the placental glutathione transferase in vitro both as substrates and as inhibitors. Since, however, the observed Km and KI values of the steroids are far above the values of their concentrations in the placenta, these interactions are of only minor physiological relevance. PMID- 3348886 TI - Dipeptidyl peptidase III from human erythrocytes. AB - Purification procedure for dipeptidyl peptidase III (DPP III) from human erythrocytes cytosol, entailing separations on DEAE-cellulose, hydroxylapatite and Sephacryl S-200 column, which gave homogeneous preparation in 35% yield, is described. The enzyme was shown to be a monomeric acidic protein (Mr approximately 82,000, pI approximately 4.5-4.6), sensitive to freezing and temperatures above 40 degrees C. It was inhibited by metallo-chelators and sulphydryl reagents, the activity being restored by divalent cations and thiol compounds. Co2 and Zn2 at low concentrations activated the enzyme, most probably by binding at the same site. Co2 prevented DPP III inactivation by di(4 pyridyl)disulfide, indicating that it is a metallo-peptidase with essential SH groups which might be near or at the binding site for the metal. Among various naphthylamides Arg-Arg-2-naphthylamide was the best substrate (Km = 7.7 microM, kcat = 28 s-1) of the enzyme. DPP III from human erythrocytes hydrolysed also tri to decapeptides of different composition, provided they did not have proline at P1 or P'1 position. A hydrophobic residue at P'1 was preferred. Among substrates were angiotensins and Leu-enkephalin. The enzyme showed particularly high affinity for angiotensin III. PMID- 3348887 TI - The primary structure of the hemoglobin of the Indian false vampire (Megaderma lyra, Microchiroptera). AB - The hemoglobin of the Indian false vampire Megaderma lyra contains only one component. In this paper, we are presenting its primary structure. The globin chains were separated by high-performance liquid chromatography and the sequences determined by automatic liquid and gas phase Edman degradation of the chains and their tryptic peptides, as well as of the prolyl-peptides obtained by acid hydrolysis of the Asp-Pro bond in the alpha- and beta-chains. The alpha-chains show 23 and the beta-chains 20 exchanges compared with the human alpha- and beta chains, respectively. In the alpha-chains, three exchanges involved alpha 1/beta 1 contacts. In the beta-chains one heme-and three alpha 1/beta 1 contacts are exchanged. The functional and systematic aspects of these replacements are discussed. PMID- 3348888 TI - 64. Konferenz der Gesellschaft fur Biologische Chemie. 6th Workshop on Plant Lipids. Hannover, September 24-26, 1987. Abstracts. PMID- 3348890 TI - [Personal opinion. Position of the League against Alcohol in Traffic on the promille limit]. PMID- 3348889 TI - Biosynthesis of gangliosides from asialogangliosides in rat liver Golgi vesicles. AB - Biosynthesis of glycolipids GA2, GA1, GM1b, and GD1c was studied in Golgi vesicles isolated from rat liver. Sequential addition of N-acetylgalactosamine, galactose and two sialic acid residues to lactosylceramide led to the endproduct GD1c. Activities of the corresponding glycosyltransferases were shown to be present in isolated Golgi vesicles and their respective kinetic data were determined. The products of each reaction were characterized by their mobility on thin-layer chromatography, by enzymic degradation to their respective precursors, and in case of GM1b by FAB mass spectrometry. PMID- 3348891 TI - [The possibility of false labeling of alcohol blood samples]. PMID- 3348892 TI - [Validity of driver fitness studies in repeatedly apprehended drunk drivers]. PMID- 3348893 TI - Use of facial osteotomies for aesthetic and reconstructive contouring. PMID- 3348894 TI - Variations in surgical anatomy of the endolymphatic sac. AB - Twenty-nine specimens of the extraosseous portion of the human endolymphatic sac (ES) were serially sectioned longitudinally. The length and width of the extraosseous ES were measured and the surface area was calculated. As the specimens included the sigmoid sinus (SS), the relationship between the ES and the SS was analyzed. The extraosseous ES varied considerably in size. The lumen either consisted of a single tube or was subdivided into several tubules. The distal part of the ES overlapped the SS in one third of the specimens. The results indicate that a minute extraosseous ES could explain the sometimes difficult task of localizing this structure at ES surgery. The great variability in size might perhaps also explain the varying results of this surgery. PMID- 3348895 TI - Conchomeatoplasty for chronic otitis externa. AB - Chronic moisture is a major cause of chronic otitis externa (COE). Moisture combined with inadequate lubrication of the stratum corneum and retention of keratin debris promote bacterial and fungal growth. In most cases of COE, creating a well-aerated, dry, self-cleaning external auditory canal prevents further infection. This can usually be accomplished by medical treatment that includes suction and swabbing. Antibiotic-steroid ear drops control infection and inflammation. Alcohol flush and warm-air ventilation dry the canal, and a hydrophobic cream lubricates and seals the stratum corneum from moisture, fungus, and bacteria. An anatomic variation, a narrow external auditory meatus leading to poor ventilation, is frequently associated with COE, which does not respond to conventional therapy. A previously unreported simple lateral conchomeatoplasty is presented. No other described meatoplasty corrects both the conchal cartilage projection and inadequate meatal skin circumference which, together, cause the small meatus. The lateral conchomeatoplasty has been used by this author for over 20 years on 35 ears. All patients showed improvement; most had complete control. PMID- 3348896 TI - The Rinne test for conductive deafness. A critical reappraisal. AB - The Rinne tuning fork test for the detection of conductive hearing loss is the most widely used tuning fork test in clinical medicine. However, the frequency of the tuning fork used to perform the test has not been standardized. In a study of 200 patients with known air-bone gaps, we found that the 256-Hz tuning fork was more sensitive than the 512-, 1024-, and 2048-Hz tuning forks for discriminating conductive from sensorineural hearing deficits. However, the occurrence of false positive responses limits its usefulness. Therefore, we believe that the 512-Hz tuning fork should become the standard tuning fork used in performance of the Rinne test to screen patients for conductive hearing loss. PMID- 3348897 TI - Conservation surgery for T2 and T3 carcinomas of the supraglottic larynx. AB - The treatment of choice for supraglottic carcinomas of intermediate size (stages T2 and T3) remains controversial. Between 1974 and 1983 in our institution, 139 patients with supraglottic carcinoma of intermediate size were judged retrospectively to have been technically amenable to conservation surgery. Primary disease control at three years was achieved in 100% of the patients treated by supraglottic laryngectomy, 91% (34 patients) of those treated by total laryngectomy, and 69% (81 patients) of those treated by radiotherapy. Of the latter group, 62% were salvaged by total laryngectomy yielding a net three-year local control of 85%. Determinate five-year survival rates were 89% for supraglottic laryngectomy, 78% for total laryngectomy, and 70% for radiotherapy. Significant problems with aspiration occurred in four patients (16%) who were treated by conservation surgery, and two patients (8%) required a permanent tracheostomy. The results of this study show that supraglottic laryngectomy with postoperative radiotherapy as indicated is a highly effective method for the local control of supraglottic carcinoma of intermediate size that is amenable to conservation surgery. PMID- 3348899 TI - Three-dimensional computed tomography in maxillofacial surgical planning. AB - Fifty-four maxillofacial three-dimensional computed tomographic examinations were performed during a 12-month period for the purpose of surgical planning. Pathologic entities in the series included trauma, neoplasia, cleft palate, and other developmental anomalies. Computer-assisted mandibular disarticulation was performed routinely after each study to permit direct viewing of the mandible or maxilla in isolation. Three-dimensional computed tomography is a useful technique for maxillofacial surgical planning. PMID- 3348898 TI - Radiosensitivity of head and neck cancer cells in vitro. A 96-well plate clonogenic cell assay for squamous cell carcinoma. AB - Radiation sensitivity was determined for nine University of Michigan squamous cell carcinoma (UM-SCC) cell lines, MCF-7 and HeLa, using a 96-well plate clonogenic assay. Plating efficiencies (PE) of the UM-SCC cell lines were between 0.16 and 0.36. Higher PE values obtained were with MCF-7 (0.4) and HeLa (0.5). The UM-SCC cell lines were used at low passages (passage 13 to passage 20) to minimize artifacts attributable to long-term culture. Cells were irradiated in suspension using a cobalt 60 gamma source at a dose rate of 0.94 Gy/min (94 rad/min). Survival data were fitted well by either a linear quadratic function F = e-(alpha D + beta D2) or by a monoexponential function F = Ae-alpha D. Mean inactivation dose, equivalent to the area under the survival curve (AUC), was used as a measure of radiation sensitivity. The UM-SCC-1, 9, 11A, 11B, MCF-7, and HeLa were the most radiation resistant lines we tested (AUC greater than 2.1), while UM-SCC-14A was the most sensitive (AUC = 1.591). The assay was highly reproducible, and the difference in radiation sensitivity between cell lines were statistically significant. PMID- 3348900 TI - Comparison of bronchoalveolar lavage fluid recovered during bronchoscopy with local or general anesthesia. AB - Bronchoalveolar lavage (BAL) is a diagnostic technique through which information is obtained about conditions in peripheral parts of the bronchoalveolar tree. To determine the impact of general anesthesia on BAL fluid composition, nine patients underwent BAL while under general anesthesia and 16 healthy controls had BAL with local anesthesia. The percentage of recovered fluid and total cell counts were significantly lower in patients under general anesthesia than in controls. The number of viable cells, the proportions of the various cells, and the BAL albumin-serum albumin ratio did not differ between the groups. Thus, general anesthesia with controlled ventilation, as performed in this study, apparently does not seriously after the prerequisites for BAL. PMID- 3348901 TI - Evaluation of the orbital floor in zygoma fractures. AB - Displaced fractures of the zygoma require reduction to prevent malunion. The indications for concomitant orbital floor exploration are controversial. In a retrospective review, the preoperative clinical findings, roentgenographic findings, and mode of injury in 106 patients with zygoma fractures who had their orbital floors explored was compared with surgical findings. The finding of preoperative diplopia was correlated with a surgically significant floor defect. The finding of trismus correlated with the absence of a significant defect. No other clinical or roentgenographic finding was correlated to a significant degree with the presence or absence of a significant defect. PMID- 3348902 TI - Giant cholesterol cysts of the petrous apex. AB - The giant cholesterol cyst is a clinical entity distinct from cholesterol granulomas and other destructive lesions of the petrous bone. Preoperative assessment by computed tomographic scan and magnetic resonance imaging is extremely helpful. Attempts at total resection of the lesion are not necessary. Adequate surgical drainage may be established through the mastoid or middle fossa. PMID- 3348904 TI - Physiologic exclusion of the injured esophagus. AB - Despite continuing advances in the surgical and nutritional management of esophageal perforation, morbidity and mortality remain significant. Described within is the successful management of two such cases by the physiologic exclusion of the esophagus. By this, we mean distal decompression and proximal diversion and decompression through a gastrostomy and cervical esophagostomy. This provides the greatest chance for protection of the esophageal suture line repair. PMID- 3348903 TI - Skull metastases from follicular thyroid carcinoma. AB - Distant metastatic disease from thyroid carcinoma is becoming a rare problem. Physicians and the public are increasingly aware of minimally invasive methods of early diagnosis of thyroid malignancy, such as fine-needle aspiration with cytologic examination. Total thyroidectomy itself has become less associated with morbidity than it once was. We describe three patients with follicular thyroid carcinoma metastatic to the skull who were seen recently. Two of these patients had masses neglected for 20 and 50 years, respectively. The management of this disease entity is discussed. PMID- 3348905 TI - Pathologic quiz case 2. Hemangiopericytoma (HP) of the nasal cavity. PMID- 3348906 TI - Pathologic quiz case 1. Olfactory neuroblastoma. PMID- 3348907 TI - Cricopharyngeal myotomy with laryngectomy. PMID- 3348908 TI - Recurrent antral polyp through antrostomy. PMID- 3348909 TI - Nasopharyngeal secretory immunoglobulins in children with recurrent acute otitis media and secretory otitis media. AB - Secretory IgA (SIgA) and secretory IgM (SIgM), total IgA and total IgM were measured in plasma and nasopharyngeal secretions (NPS) from young children with different degrees of otitis proneness. Significantly higher levels of plasma IgM and lower levels of NPS-SIgM were found in children with recurrent episodes of acute otitis media (rAOM) compared with children suffering from secretory otitis media (SOM) and healthy controls. Both plasma IgA and NPS-SIgA were evenly distributed in the three groups of children investigated, and in most children the levels of NPS-SIgA exceeded plasma IgA levels. Plasma SIgA was significantly increased in children with rAOM and SOM, probably resulting from frequent occurrence of inflammatory events at the nasopharyngeal level. No correlation could be demonstrated between NPS-SIgA and plasma IgA, or between NPS-SIgM and plasma IgM. Also, for both NPS-SIgA and NPS-SIgM, there was no correlation with age. A negative correlation was observed between the transudation index of albumin to the nasopharynx and the ratio of NPS-SIgA to total NPS-IgA. A ratio of 1 (100%) corresponded to a transudation index of 8%. The ratios of NPS-SIgA to total NPS-IgA varied considerably and a range of 39%-88% could only to some extent be explained by transudation of plasma IgA to NPS. The results of the present study show that the children with rAOM and SOM are well furnished with locally produced SIgA antibodies at the nasopharyngeal level. In children with SOM, the nasopharyngeal hypofunction in the case of low NPS-SIgM seems to be less pronounced compared with that of otitis-prone children. PMID- 3348910 TI - Use of anti-seminoma monoclonal antibody to confirm the diagnosis of mediastinal seminoma. A case report. AB - Chest x-ray in a 20-year-old man showed a large anterior mediastinal mass and a needle aspirate was diagnosed by light microscopy (LM) as non-Hodgkin's lymphoma. Treatment with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) was ineffective and a tissue biopsy was performed. LM showed large, non-cohesive cells with abundant cytoplasm and rounded nuclei. Differential diagnoses included malignant lymphoma, seminoma, thymoma, anaplastic carcinoma, malignant melanoma and paraganglioma. Electron microscopy was not conclusive and immunoperoxidase staining was carried out. The malignant cells were negative for common leukocyte antigen, Leu M1, alpha-fetoprotein, chorionic gonadotrophin, cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, S-100 protein and neuron specific enolase but positive for placental alkaline phosphatase. In addition, there was strong positivity with a monoclonal antibody (mAb) which was recently shown to react with testicular seminomas. This case illustrates the value of this mAb in confirming the diagnosis of mediastinal seminoma. PMID- 3348911 TI - Characteristics of two malignant lymphomas in C57B1/6J mice. Cytogenetic changes and the distribution of i.v. transfused tumor cells with and without enzyme (pronase, neuraminidase) treatment. AB - Two T-cell lymphomas induced by a combination of antigen stimulation and immunosuppression in inbred C57Bl/6J mice, BWL1 and BWL2 (Ryd et al. 1985), were further characterized. Cytogenetically they have the same trisomy 15 abnormality as chemically, virally and radiation induced T-cell lymphomas. Analyses of early and late tumour generations indicate that both tumours are chromosomally stable. After i.v. transplantation, the two tumors grew in a similar manner and preferentially in spleen and liver. Proteolytic treatment of the tumor cells changed the distribution of both lymphomas from the lungs to other organs. Neuraminidase treatment had no such effect on BWL2, but a similar but weaker effect than pronase on BWL1. Our findings support the notion that the distribution of lymphomas are, at least in part, governed by cell-surface characteristics. PMID- 3348912 TI - Tumours in Iceland. 10. Malignant tumours of the female breast. A histological classification, laterality, survival and epidemiological considerations. AB - The Icelandic Cancer Registry has records of 1,720 cases of malignant tumours of the female breast diagnosed in 1,659 patients in the 30-year period 1955-1984. Of these, 1,658 tumours were invasive. Sufficient histological material existed for 1,666 malignant tumours to make it possible to classify them according to the criteria published by the WHO. The most frequent histological type was Ductal carcinoma: 1,064 neoplasms, or 64%. Second in frequency was Lobular carcinoma: 175 neoplasms, or 10%; third was Mucinous carcinoma: 115 neoplasms, or 7%; and fourth in frequency was Medullary carcinoma: 69 neoplasms, or 4%. The incidence of carcinoma of the breast increased by 74% from 37.0 per 100,000 per annum in 1955-59 to 64.4 per 100,000 in 1980-84. This increase in incidence affected all morphological types, but Lobular and Mucinous more than Ductal and Medullary. The survival times have improved with time. Unilateral tumours were 710 in the right and 837 in the left breast. Both breasts were involved 167 times (106 patients), and in 6 patients the side was not recorded. A second primary was more likely to develop when the first one was in the right breast. This study of malignant tumours of the breast is the tenth in a series of investigations into histological classification of tumours occurring in Iceland. PMID- 3348913 TI - On the effect of Al(OH)3 as an immunological adjuvant. AB - Using a mice in a tetanus vaccination system, we have examined the mode of action of the immunological adjuvant, aluminium hydroxide (Al(OH)3), on antibody titers as measured by an ELISA-method. A profound effect of the adjuvant was observed after primary immunizations, increasing titers about 100-fold compared to plain (not adjuvanted) controls. However, no effect on titers could be attributed to a content of Al(OH)3 in the vaccines when used for booster immunizations, as the increase in titers after boosting was either the same for groups given plain or adsorbed toxoids, or even higher in the groups receiving the plain vaccine. Thus, the effect of Al(OH)3 as an adjuvant seems to be exerted mainly on the primary antibody response. Investigating the mode of action by the adjuvant, we adsorbed a certain amount of toxoid onto varying doses of Al(OH)3. An antigen ELISA revealed that all toxoid had been adsorbed to the Al-gel in the preparations. The antibody titers after immunization showed a significantly higher response to toxoid adsorbed to the higher amount of adjuvant, indicating that this effect was most probably due to free, not antigen-bound, Al-particles. Moreover, this effect could be inhibited when BSA was added in excess to the preparation, thereby blocking the free residues on the Al-gel. PMID- 3348914 TI - Construction and characterization of complementary DNA libraries from Vero cells infected with measles virus. AB - Several cDNA libraries have been generated from poly(A)RNA from Vero cells infected for 24 hours with measles virus. Different protocols for cDNA library construction were compared and some critical steps were evaluated. From these libraries, a measles virus specific sequence corresponding to 885 of 1600 nucleotides of the measles virus phosphoprotein gene has been cloned. The phosphoprotein gene accounts for 1% of the total cDNA library after 24 hours of infection at 37 degrees C. The technique of differential colony hybridization was used to analyze the distribution and change of the poly(A)-RNA expression in uninfected Vero cells and in cells infected with measles virus for 24 hours. PMID- 3348916 TI - [A study of benign epilepsy of children with centro-temporal EEG foci, with special reference to clinical course and rolandic discharge]. PMID- 3348915 TI - Bacteria of the gastric antrum and their relation to chronic gastritis. AB - Biopsy samples from the gastric antrum were taken from 61 patients. On bacteriological culture, Campylobacter pylori was isolated in 27 subjects. Thirty four patients had chronic gastritis, as seen in routine-stained histological sections. By means of the May-Grunwald-Giemsa (MGG) staining technique, bacteria were demonstrated in sections from 26 subjects. Of these, 22 had gastritis histologically. In 13 subjects, structures similar to Campylobacter pylori were found in MGG-stained sections, 11 of these having chronic active gastritis histologically. Scanning electron microscopy demonstrated bacteria with the typical appearance of Campylobacter pylori, but other types of bacteria were also found, both on electron microscopy and on bacteriological culture. The study confirms that there is an increased frequency of histological gastritis when Campylobacter pylori is present in the samples (p = 0.009). However, a causative role of the bacteria could not be demonstrated in this study, and bacterial penetration into the epithelium was not observed. PMID- 3348917 TI - [A long-term follow-up study on a case with glycine encephalopathy]. PMID- 3348918 TI - [A case of nephrogenic diabetes insipidus with intracerebral calcification]. PMID- 3348919 TI - [Development of the human fetus cerebellum: a volumetric study of the cerebellar structures]. PMID- 3348920 TI - [A case of lissencephaly syndrome (pachygyria)--electrophysiological study]. PMID- 3348921 TI - [Transient improvement of the West syndrome in two cases following rotavirus colitis]. PMID- 3348922 TI - [A case of transethmoidal encephalocele with recurrent bacterial meningitis]. PMID- 3348923 TI - [Analysis of normal F-wave of the tibial nerve in childhood]. PMID- 3348924 TI - The diagnosis of MH: its social implications. PMID- 3348925 TI - Proceedings of the Anaesthetic Research Society. London meeting. November 13-14, 1987. Abstracts. PMID- 3348926 TI - Avoiding accidental dural punctures. PMID- 3348927 TI - Modified i.v. cannula used for nerve stimulation. PMID- 3348928 TI - Failure to demonstrate in vitro metabolism of morphine in whole blood and plasma. PMID- 3348929 TI - Opioid premedication and biliary colic (the first indication of biliary pathology) PMID- 3348930 TI - Suxamethonium and intraocular pressure. PMID- 3348931 TI - Anti-neoplastic synergism of nitrous oxide and methotrexate. PMID- 3348933 TI - I miss you, nurse. PMID- 3348932 TI - Does 2 + 2 = 4? ADN programs as beginning preparation for professional nursing. PMID- 3348934 TI - "Noncompliance": is this diagnosis ethical? PMID- 3348935 TI - Music soothes the troubled soul.... PMID- 3348936 TI - What image do you display? PMID- 3348938 TI - Occupational health. PMID- 3348939 TI - From the patient. PMID- 3348937 TI - Nursing in process: stress in nursing school. PMID- 3348940 TI - Urinalysis: what do those numbers mean? PMID- 3348941 TI - Serum thyroglobulin as a preclinical tumour marker in subgroups of thyroid cancer. AB - Serum samples from a biological serum bank taken several years before the diagnosis of cancer, were analysed for S-Tg and S-TSH in 43 patients with thyroid cancer and compared to 128 healthy controls matched for age, sex, geographical region and time of blood sampling. The main finding was the difference in S-Tg between cases and controls, the highest values being found in sera from cases. Relative risk of thyroid cancer increases with increasing S-Tg levels (the global test giving P less than 0.0005). Extremely high levels were found in 4 cases with follicular and 3 with anaplastic cancers. No such statistically significant difference was found in S-TSH concentration. Possible explanations for the elevated S-Tg observed several years before clinically evident malignant tumour are discussed. PMID- 3348943 TI - Phase II evaluation of mitozolomide in ovarian cancer. PMID- 3348942 TI - Who should measure quality of life, the doctor or the patient? AB - The extent to which a doctor or health professional can make a valid assessment of a patient's quality of life, anxiety and depression was investigated in a series of cancer patients. Doctors and patients filled out the same forms, viz. the Karnofsky, Spitzer, Linear Analogue Self Assessment Scales and a series of simple scales designed for this study, at the same time. Correlations between the two sets of scores were poor, suggesting that the doctors could not accurately determine what the patients felt. A further study examining the reproducibility of these scales demonstrated considerable variability in results between different doctors. It is concluded that if a reliable and consistent method of measuring quality of life in cancer patients is required, it must come from the patients themselves and not from their doctors and nurses. PMID- 3348944 TI - Tamoxifen in refractory ovarian cancer: the use of a loading dose schedule. PMID- 3348945 TI - Tumour karyotype discriminates between good and bad prognostic outcome in neuroblastoma. AB - In 28 patients with neuroblastoma of different stages the karyotype was determined in the primary tumour and/or in the metastases by direct chromosome preparation or short term cell culture. In addition, DNA analysis for the proto oncogene N-myc was performed for comparison in 10 cases. Abnormalities (deletions, translocations, derivations) of the short arm of chromosome 1 with the most frequent breakpoint at 1p32 (besides rarer aberrations in other chromosomes) were found in the tumour karyotype of 15 of 18 (83%) patients with metastatic disease (stage IV) and in 2 of 3 patients with stage III, but in none of the 7 patients with stages I, II, IV-S who are all alive with no evidence of disease. These 7 surviving patients with good prognosis had a hyperploid tumour karyotype, mainly in the triploid range. Eleven of the 18 (61%) patients with stage IV and 1 of 3 patients with stage III also contained double minutes (DMs) and/or homogeneously staining regions (HSRs) in their tumour karyotypes. N-myc amplification (30 to 60 copies) in the tumour DNA was detected in 2 of 6 (33%) examined cases with stage IV, in 1 out of 2 examined cases with stage III, and correlated with the presence of DMs/HSRs. Life table analysis showed a 90% probability of surviving in patients lacking the 1p abnormality as compared to less than 10% in patients with an aberrant 1p chromosome in the tumour cells. We conclude that tumour karyotype, in particular the structure of the short arm of chromosome 1, is the most important factor in determining the different outcome in children with neuroblastoma. PMID- 3348946 TI - Parental cancer in an unselected cohort of children with cancer referred to a single centre. AB - A study of parental cancer in 326 children referred to a single Paediatric Oncology Unit found a significant increase in breast cancer in mothers of children with solid tumours. The 5 tumours found were 8.9 times the expected number. This increase could not be accounted for by any of the known risk factors for breast cancer. The incidence of cancer in mothers of leukaemic children and in all groups of fathers was not significantly raised. Further prospective studies in the mothers of young children with soft tissue tumours are needed to clarify the groups at risk and to determine whether counselling and surveillance of these mothers is appropriate. PMID- 3348948 TI - Structure and expression of c-myc and c-fos proto-oncogenes in thyroid carcinomas. AB - Tumour specimens from 23 patients with thyroid carcinoma, 22 patients with thyroid adenoma, 3 with Graves' disease, and tissues from 8 normal thyroid glands were analyzed by Southern blot hybridization for the physical state of c-myc and c-fos proto-oncogenes. In 4 patients, both the primary tumour and lymph node metastases were analyzed. No amplification or rearrangement of the two proto oncogenes was detected. Total RNAs were also analyzed. Elevated levels of the 2.4 kb c-myc RNA and of the 2.2 kb c-fos RNA were found in 13/23 (57%) and 14/23 (61%) of the cancer patients, respectively. High levels of c-myc transcripts were more frequently found in thyroid carcinomas with unfavourable prognosis. Concomitant elevated levels of both c-myc and c-fos RNAs were found in 8 cancers. High levels of c-myc RNA were also found in 1 out of 22 specimens of adenoma, in 1 specimen of Graves' disease and in 2 normal thyroid glands. High levels of c fos RNA were found in 20 of the 22 adenoma samples and in 2 out of 8 normal thyroid tissues. These data indicate that the overexpression of c-myc and c-fos genes is independent of an alteration of the loci. The high levels of c-fos found in adenoma may be associated with the differentiation state of these tumours. PMID- 3348949 TI - Radiation survival of murine and human melanoma cells utilizing two assay systems: monolayer and soft agar. AB - The radiation response of murine and human melanoma cells assayed in bilayer soft agar and monolayer was examined. Cells from the murine melanoma Cloudman S91 CCL 53.1 cell line and three human melanoma cell strains (C8146C, C8161, and R83-4) developed in our laboratory were irradiated by single dose X-rays and plated either in agar or on plastic. D0 values were the same within 95% confidence intervals for cells from the human melanoma cell strains C8146C, C8161, and R83-4 but were dissimilar for the murine cell line CCL 53.1 Dq values were different for all cells studied. The shape of the survival curve for all four melanomas was not identical for cells assayed in soft agar versus cells grown on plastic. This would indicate that apparent radiosensitivity was influenced by the method of assay although there were no apparent consistent differences between the curves generated by monolayer or bilayer soft agar assays. PMID- 3348951 TI - Sequence in hearing impaired children's development of concepts. PMID- 3348952 TI - The relationship between school type and adolescent self esteem, attribution styles, and affiliation needs: implications for educational outcome. PMID- 3348947 TI - Mechanisms of organ selective tumour growth by bloodborne cancer cells. AB - The sites of tumour development for 6 rat tumours injected into syngeneic rats via different vascular routes was determined. Xenografts of human tumours were also injected intra-arterially (i.a.) into immunosuppressed rats. Following intravenous (i.v.) and intraportal (i.ptl.) injection of cells tumour colonies localized in lung and liver respectively due to tumour cell arrest. Arterially injected radiolabelled cells disseminated and arrested in a similar distribution to cardiac output and did not 'home' to any organs. Following arterial injection of unlabelled tumour cells colonies grew in many organs. While the pattern of growth for a particular tumour varied with the cell dose, the 'arterial patterns' for all of the tumours studied followed a similar pattern. Some organs (eg adrenals, ovaries and periodontal ligament) were consistently preferred, others (eg skin and skeletal muscle) only supported tumour growth following the delivery of large numbers of cells, while in some tissues (eg spleen and intestines) tumour never grew. Viable tumour cells could be demonstrated by bioassay in many organs for up to 24h after i.a. injection. However tumour growth only occurred in certain organs and the pattern of this growth was not related to the number of tumour cells arrested or their rate of autolysis. This site preference could be expressed quantitatively as the probability of an arrested cell developing into a tumour and was considered a 'soil effect'. Site preference was not directly related to organ vascularity. Organ colonisation was promoted by steroid treatment but the mechanism was unclear and was not secondary to T-cell immunosuppression or prostaglandin synthesis suppression. The adrenal glands were preferred sites of tumour growth but pharmacological manipulation of adrenal function did not alter tumour growth to this organ. Sites of injury and healing were preferred sites of tumour colonisation and this could not be accounted for by increased delivery of tumour cells to these regions. The possibility that the macrophage component of the inflammatory response promoted tumour growth was suggested from studies in which the interval between trauma and inoculation of tumour cells was varied as well as by promotion of intraperitoneal (i.p.) tumour growth by a macrophage infiltrate. PMID- 3348950 TI - Immunohistochemical localization of chondroitin sulphate and dermatan sulphate proteoglycans in tumour tissues. AB - Immunohistochemical localization of chondroitin sulphate and dermatan sulphate proteoglycans (PGs) was observed in 70 tumour tissues, using monoclonal antibodies 9A-2 and 3B-3 raised against core molecules obtained from chondroitin sulphate PG by chondroitinase ABC-treatment. They recognize a stub of delta Di-4S and delta Di-6S binding to core protein via a linkage tetrasaccharide, respectively. The antibody 6B6 raised against dermatan sulphate PG obtained from an ovarian fibroma capsule in our laboratory was also used. The interstitial fibrous elements, so-called 'specific stroma' within the cancer cell nests contained chondroitin 4-sulphate PG as revealed with 9A-2, whereas the surrounding connective tissue and the preexisting fibrous connective tissue involved in the tumour growth consisted of dermatan sulphate PG with a considerable amount of chondroitin 4-sulphate PG. Chondroitin 6-sulphate PG as revealed with 3B-3 was located in the connective tissue proliferating from blood vessels and muscle tissue in association with the invasive growth of tumour cells. Chondroitin 6-sulphate PG was also observed in the basement membrane components of some tumours. In non-epithelial tumours (fibrogenic, chondrogenic, osteogenic and neurogenic tumours), chondroitin 4-sulphate was in fibrous portions. When collagenization and hyalinization progressed, dermatan sulphate PG was observed to increase in quantity. PMID- 3348954 TI - Effects of polymorphonuclear leucocyte depletion on the pathogenesis of experimental Legionnaires' disease. AB - Guinea-pigs were depleted of circulating polymorphonuclear leucocytes (PMN) by administration of anti-polymorph serum. Groups of animals were then infected by aerosols containing different doses of Legionella pneumophila and the effects compared with those in intact infected controls. Elimination of PMN lowered the dose of L. pneumophila necessary to establish infection, increased bacterial numbers in the lungs and caused much higher mortality. It did not change the nature or extent of pulmonary lesions. The findings confirm the importance of PMN in defence of the lung against L. pneumophila infection and indicate that PMN and their enzymes are not responsible for the pulmonary lesions, which are probably caused directly by the bacteria. PMID- 3348953 TI - Quantitative interactions in weight of lymphoid organs and steroid hormonal organs in hamsters under several experimental conditions. AB - The adrenal and gonadal steroid hormones may continue to regulate lymphoid cells in tissues of mammals throughout their life span. To examine quantitative interrelationships between the endocrine and immune systems, we measured weights of the organs and compared them. The results showed that: (1) The relative weight of the adrenals in adult male hamsters significantly exceeded that of age-matched females. The adult thymus and spleen were heavier in females. (2) Adult gonadectomy induced marked involution of the thymus and adrenal hypertrophy in both sexes. (3) A single oestrone injection at suckling has severe, long lasting effects, with gonadal atrophy and hypertrophy of lymphoid tissues in both sexes for I year. (4) Testosterone in the same way produced adrenal hypertrophy in female hamsters, and adrenal atrophy in males. (5) Thymectomy, at 3 weeks of age, resulted in marked atrophy of the gonads in late adulthood in both sexes. (6) Repeated pulses of cortisone acetate led to marked involution of the thymus and steroid organs, the adrenals and testes. The rather unexpected results, as in (2), (3) and (5), probably represent the ultimate consequence of serial interactions among these organs after treatment. These findings suggest that there is thymus-gonads interdependence even in adulthood, and that subtle counterbalancing co-operation between the adrenals and gonads may regulate lymphocyte functions in tissues. between the adrenals and gonads may regulate lymphocyte functions in tissues. PMID- 3348955 TI - The relationship between cell-mediated immunity and cartilage degradation in antigen-induced arthritis in the rabbit. AB - The relative contributions of cellular and humoral immunity to cartilage destruction in chronic arthritis has been investigated in a model of chronic synovitis in the rabbit. In this model, antigen-induced arthritis, immunization with ovalbumin in Freund's complete adjuvant (FCA) followed by intra-articular injection of this protein produces a chronic synovitis associated with loss of proteoglycan from articular cartilage. In addition, the synovial lining cell population is metabolically activated. Similar treatment of animals immunized with ovalbumin in Freund's incomplete adjuvant (FIA) produced a resolving arthritis which initially (over the first 7 days) appears to be identical to that in FCA-immunized animals, apart from the lack of activation of synovial lining cells. Following this initial synovitis the joints return to apparent normality apart from a persistent 'low grade' synovitis consisting mainly of a plasma cell infiltrate. The most striking finding in the FIA-immunized animals is the rapid loss (greater than 30% by day 7) and recovery of proteoglycan from the matrix of articular cartilage. These findings show that the perpetuation of chronic destructive synovitis in the rabbit requires the presence of active cellular immunity. PMID- 3348956 TI - Induction of amyloid enhancing factor and its biological properties in murine alveolar hydatidosis. AB - The biological activity and time of appearance of alveolar hydatid cyst induced splenic amyloid enhancing factor (AEF) with respect to amyloid deposition in the spleens were determined in C57BL/6J mice. Mice were infected intraperitoneally with 100 alveolar hydatid cysts (AHC) and killed bi-weekly between 2 and 14 weeks postinfection (p.i.). AHCs and spleens were excised, weighed and a portion of each spleen was sectioned and stained for quantitation of amyloid deposits and histological studies. The remaining spleen pieces were sonicated separately in cold phosphate buffered saline, pH 7.4 (I g/10 ml), centrifuged (27,000 g, 60 min, 4 degrees C) and the supernatant tested for AEF activity. Splenomegaly followed the progressive increase in the AHC biomass and AEF activity coincided with the appearance of amyloid deposits at 6 weeks p.i. A 2.5 mg intraperitoneal protein dosage of AEF in conjunction with a subcutaneous injection of 0.5 ml of a 0.11 M AgNO3 solution in mice, induced the maximum amount of splenic amyloid deposition at 48 h; the amount of splenic amyloid deposits decreased by either increasing or decreasing the AEF dosage. In vivo, 70% of the AEF activity was abolished by day 4 post-injection of AEF and completely by 3 weeks. These findings indicate that AHC-induced AEF is functionally analogous to casein induced AEF and its appearance in the spleen coincides with neutrophilia, histiocytosis and amyloid deposition. PMID- 3348957 TI - The relationship between faecal bile acids and the development of experimental colon cancer. AB - Human metabolic studies have suggested a positive association between dietary intake, faecal bile acid excretion and the development of colon cancer. Similar investigations in experimental models of this disease have also implicated faecal bile acids but in both animals and man the results remain equivocal. This study sequentially examines the outputs and concentrations of faecal bile acids in dimethylhydrazine (DMH) treated groups of rats (n = 10), killed at 5-weekly intervals from the 10th to 40th week following the first injection. The sequential results showed that both the output and concentration of faecal bile acids decreased with time and accompanied an increase in both the incidence and numbers of colonic neoplasms over the 40 weeks of the study. When the animals were grouped according to the histological classification of their tumours, the faecal bile acids did not differ between animals with and without tumours. Further, when the latter group were sub-divided into those with adenomas alone and those with carcinomas, faecal bile acid outputs and concentrations did not differ between them, nor when they were compared with the tumour-free animals. The results of this study do not support a role for faecal bile acids in the dimethylhydrazine-induced model of experimental colon cancer in rats. PMID- 3348958 TI - The effect of dietary protein restriction on high dose gentamicin nephrotoxicity in rats. AB - Gentamicin (120 mg/kg/day) was administered for 10 days to Sprague-Dawley rats given either a low (5% w/w) or normal (18% w/w) protein diet. Serum protein concentrations remained normal in all rats during the study. Nephrotoxicity was slightly less severe in rats fed a low protein diet as shown by: (i) a mean creatinine clearance rate (14 +/- 4 ml/min) which was significantly greater than that (8 +/- 3 ml/min) recorded from the rats maintained on the normal diet (P less than 0.05); (ii) lower activities of urinary N-acetyl-beta-D glucosaminidase (NAG); and (iii) less marked histological changes. Mean tissue concentrations of gentamicin were considerably lower in both renal cortex and medulla from rats maintained on the low protein diet than from those animals on the normal diet (P less than 0.01 and P less than 0.05, respectively). These differences were, however, not reflected in the mean trough serum gentamicin concentrations which were not significantly different between the two groups. These results are discussed in relation to the proposed mechanisms involved in gentamicin-induced nephrotoxicity. PMID- 3348959 TI - Ceroid accumulation by murine peritoneal macrophages exposed to artificial lipoproteins: ultrastructural observations. AB - Murine resident peritoneal macrophages were maintained in cell culture in a medium containing 10% lipoprotein-deficient fetal calf serum to which various artificial lipoprotein particles (coacervates of lipid and bovine serum albumin) had been added. The uptake and intracellular fate of these particles was studied by electron microscopy. The appearance of material accumulating within the cells varied according to the nature of the lipid component of the ingested particles. Lipids which are readily oxidised (cholesteryl linoleate, cholesteryl arachidonate, trilinolein) were associated with the formation of ceroid within membrane-bound structures. Less readily oxidized lipids (cholesteryl oleate, triolein) were not associated with ceroid accumulation but instead the cells contained numerous nonmembrane-bound lipid inclusions. The appearances of the ceroid within the murine peritoneal macrophages are similar to those of ceroid in macrophages in human atherosclerotic lesions. PMID- 3348960 TI - Ultrastructure of canine lung during the proliferative phase of paraquat toxicity. AB - The herbicide paraquat induces irreversible progressive pulmonary fibrosis in human beings and animals. The mechanisms of the fibrosis are still unresolved. There is histological and ultrastructural evidence that an early destructive phase followed by a proliferative phase occurs in the lungs post paraquat exposure. In this study, lungs obtained from a dog 7 days following intravenous administration of paraquat (12 mg paraquat dichloride per kg bodyweight) are compared with lungs obtained from a normal dog. Examination included gross post mortem inspection, histology, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Comparison of the TEM of the paraquat affected canine lung with the normal showed: alveolar collapse; detachment of alveolar epithelial cells from the basement membrane; alteration of the type II alveolar cell morphology; infiltration of granulocytes and erythrocytes into both the interstitium and alveolar air spaces; and fibroblasts associated with collagen fibrils. The SEM of the paraquat-exposed canine lung, reported here for the first time, demonstrated irregular, alveolar walls with type I alveolar epithelial cell detachment, and erythrocyte and alveolar macrophage infiltration. These findings suggest that the detachment of alveolar epithelial cells and the alveolar macrophage play a significant role in paraquat-induced pulmonary fibrosis. PMID- 3348961 TI - Type 2 pneumocyte responses to cyclophosphamide-induced pulmonary injury: functional and morphological correlation. AB - We investigated the correlation between the functional and morphological responses of type 2 pneumocytes to experimentally induced subacute lung damage. BALB/c mice were injected with a single dose of 300 mg/kg of cyclophosphamide intraperitoneally to induce alveolar epithelial injury. Groups of six cyclophosphamide-treated animals and three untreated controls were killed at 3 days and 1, 2, 3, 4, 6, 8 and 12 weeks after drug treatment. The net secretory response of type 2 pneumocytes to injury was assessed by an enzyme immunoassay for the surfactant-associated protein alveolyn in bronchoalveolar lavage fluid and the morphological responses of the alveolar epithelial cells were evaluated by light and electron microscopy. Early type I pneumocyte injury occurred without significant endothelial damage and was accompanied by intra-alveolar fibrinous exudation. This was followed by focal hypertrophy and apparent hyperplasia of type 2 pneumocytes, together with the progressive accumulation of large foamy intra-alveolar macrophages and focal pleural fibrosis. In a minority of animals these lesions progressed to intra-alveolar fibrosis with marked epithelial hyperplasia. The type 2 pneumocyte response was initially paralleled by an increase in the concentration of alveolyn in bronchoalveolar lavage fluid, which was significantly greater than control values at 1 and 2 weeks (P less than 0.005) as well as at 3 and 4 weeks (P less than 0.05) after injury induced by cyclophosphamide, but thereafter fell to control levels. This study demonstrates that cyclophosphamide induces morphological alterations of type 2 pneumocytes and altered secretory activity of these cells manifested as an increased net secretion of a surfactant-associated protein. PMID- 3348962 TI - Effect of ischaemia on endothelium-dependent vasodilatation in the isolated rat superior mesenteric artery. AB - The isolated perfused rat superior mesenteric artery preparation was used to determine whether endothelium-dependent vasodilatation occurs in this vessel, and to test whether impairment of this function may contribute to post-ischaemic mesenteric vasospasm. It was found that vessels preconstricted with noradrenaline responded to optimal concentrations of acetylcholine (3 X 10(-5) M), ADP (2 X 10( 5) M) and to isolated homologous platelets (500,000/mm3) with an 84%, 85% and 37% decrease in mean perfusion resistance, respectively. In preparations treated with collagenase to denude the vessels of endothelium there was a significantly diminished response to acetylcholine and ADP (24% & 23% decrease in resistance, respectively). Platelets, on the other hand, caused a further 34% increase in resistance. A model of mesenteric ischaemia was produced by interrupting perfusate flow through the preparation for intervals of 1 to 4 h. This was associated with morphological evidence of endothelial cell damage and with a progressive decline in the responsiveness to acetylcholine and ADP. After 1 h there was also a significant reduction in the response to platelets. With intervals of ischaemia longer than 2 h platelets caused only further constriction which could be inhibited by the serotonin antagonist, methysergide. This study suggests that an altered response of the endothelium to platelet-derived vasoactive substances may contribute to the post-ischaemic vasospasm encountered during reperfusion. PMID- 3348963 TI - The dansyl chloride technique for stratum corneum renewal as an indicator of changes in epidermal mitotic activity following topical treatment. AB - Using a hypomitotic agent, triamcinolone acetonide, and a hypermitotic agent, retinyl propionate, we investigated the relationship between epidermal mitotic activity and stratum corneum renewal time of topically treated skin as determined by the dansyl chloride staining technique. Treatment with the base cream resulted in a reduction in renewal time compared with an untreated control site. The predicted increase in renewal time with the hypomitotic agent and reduction with the hypermitotic agent was only observed when daily treatment was commenced 2 weeks prior to and continued after dansyl chloride staining and not when treatment was started after staining. These results indicate that in order to use cell renewal methods to demonstrate changes in mitotic activity brought about by topical treatments, it is necessary to pre-treat the skin with the test material to establish full epidermal equilibrium at the changed mitotic state before labelling with dansyl chloride. Meaningful claims for effects on cell renewal of specific cosmetic ingredients should only be made after comparison with a base cream treated site, both having been allowed to equilibrate, rather than on the basis of comparison with untreated skin. PMID- 3348964 TI - Relationship between body weight and blood pressure and some metabolic parameters in psoriatic patients. AB - The relationship between body weight and blood pressure, total serum cholesterol, triglycerides, uric acid and glucose was investigated in 203 psoriatic patients in comparison with 904 healthy controls. In the psoriatic patients, these parameters were clearly related to their body weight. Those psoriatic patients of normal weight exhibited lower mean values of all the parameters compared with overweight psoriatic patients while they did not differ from control subjects of normal weight. Our results suggest that only overweight psoriatic patients exhibit the metabolic abnormalities frequently reported in the literature, while psoriatic patients of normal weight do not differ from the general population in this respect. PMID- 3348965 TI - A survey of the social and psychological effects of psoriasis. AB - One hundred and four consecutive patients with psoriasis who were being treated in two Dublin dermatology hospital units answered a questionnaire. Social and emotional morbidity was present for many patients despite access to modern treatment facilities. Fifty five percent of patients had never experienced a complete remission from their psoriasis. A large percentage of patients avoided common social activities, for example swimming and sports; 50% felt that psoriasis had inhibited their sexual relationships and 11% of patients said they would avoid having children in case their offspring should develop the condition. Thirty-six per cent felt the hospital doctor spent most of the consultation time writing prescriptions and 59% of patients had never been given an explanatory pamphlet or book about psoriasis. To help patients to come to terms with what is for many a lifelong condition, greater efforts should be made to improve the communication at consultation, and provide more patient education. PMID- 3348967 TI - Clinical features and course of type A and type B vitiligo. AB - Four hundred and eighty one cases of vitiligo (acquired idiopathic depigmentation) were studied clinically. They were divided into two types, type B, in which depigmented patches are confined to a definite dermatome in the same manner as herpes zoster, and type A, which included all cases of vitiligo not classified as type B. The ratio of type A:type B was approximately 3:I. Onset of type A vitiligo could occur at any age, whereas type B generally affected the young. The activity of type B vitiligo usually ceased after one year, following rapid spread over the particular dermatomal area. However, in type A vitiligo new depigmented patches continued to appear throughout the patients' lives. Association with halo naevus and Kobner's phenomenon were observed exclusively in type A. Association with diseases with a proven or suggested allergic or immunological aetiology was more often found in type A. These findings support our hypothesis that type A and type B vitiligo have a different pathogenesis and that autoimmune mechanisms play a role only in type A. PMID- 3348966 TI - Effect of PUVA on intestinal calcium absorption. AB - Intestinal calcium absorption increased significantly following 14 days of treatment with photochemotherapy (PUVA) in seven patients with chronic psoriasis. Irradiation with UVA alone over a similar period did not result in significant changes in calcium absorption in an additional seven psoriatic patients. These findings suggest that the increase in serum 25-OH vitamin D levels previously reported in patients treated by PUVA may have important biological consequences. PMID- 3348968 TI - Active participation of eosinophils in patch test reactions to inhalant allergens in patients with atopic dermatitis. AB - Intracutaneous testing and patch tests with house dust mite and grass pollen allergens were performed in patients with atopic dermatitis. Only patients with an immediate type skin reaction to house dust mite or grass pollen allergens showed a positive patch test reaction to these allergens 24-48 h after testing. Occasionally positive patch test reactions at 20 min, 2 h and 6 h were also observed. Patch test reactions were not found in normal controls or atopic patients without atopic dermatitis. Analysis of the cellular infiltrate demonstrated an influx of eosinophils into the dermis, starting from 2-6 h after patch testing. Immunostaining with antibodies against granular constituents of the eosinophils revealed that the infiltrating eosinophils were in an activated state and had lost part of their granular contents. At 24 h eosinophils also appeared in the epidermis. Electron microscopy showed that in the epidermis, some eosinophils were in close contact with Langerhans cells, suggesting a cell-cell interaction. Taken together, these results strongly suggest an active role for eosinophils in patch test reactions to inhalant allergens in atopic dermatitis patients. PMID- 3348969 TI - Manifestation of familial porphyria cutanea tarda after childbirth. AB - We report the case of a woman with hereditary porphyria cutanea tarda which manifested 3 weeks after she gave birth to her second child. The mother of the patient had also been diagnosed and treated for porphyria cutanea tarda. Reduced red cell uroporphyrinogen decarboxylase activity was found in the patient, the new-born child and the patient's mother. Normal enzyme activity was found in the patient's first child. PMID- 3348970 TI - The suitability of sunglasses used by patients following ingestion of psoralen. AB - We have investigated the types of eyewear which patients on photochemotherapy have obtained, and determined their suitability for providing adequate protection. Fifty-eight pairs of sunglasses from 53 patients were assessed. Spectral transmission was measured between 200 nm and 800 nm at 10 nm intervals. Thirty-eight pairs of glasses (66%) were found to be satisfactory. Particularly high UV transmission was recorded in 11 cases (19%), highlighting the need for increased awareness of the problem of ensuring that suitable protective eyewear is used. PMID- 3348972 TI - British Society for Investigative Dermatology. Annual meeting. Cambridge, September 1987. Abstracts. PMID- 3348971 TI - Pharmacological modulation of cold-induced pain in cutaneous leiomyomata. AB - In two patients with painful cutaneous leiomyomata, induction of pain by the application of an ice cube allowed assessment of a number of topical and systemic treatments aimed at reducing or preventing the pain. In one patient the alpha adrenoceptor blocker, phenoxybenzamine alleviated cold-induced pain. In the second patient, topical 9% hyoscine hydrobromide (an anticholinergic agent) decreased pain induced by the ice cube, but was not helpful in reducing lesional pain due to cold weather. PMID- 3348973 TI - Pemphigus foliaceus localized to the nose. PMID- 3348974 TI - Spontaneous improvement of congenital malalignment of the great toe nails. PMID- 3348975 TI - Penicillin-induced pemphigus vulgaris. PMID- 3348976 TI - Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond-Blackfan anaemia and other haematologic diseases. AB - Red-cell adenosine deaminase (ADA) activity in children with Diamond-Blackfan anaemia is significantly increased (1.91 +/- 0.90 U/g Hb) compared to that seen in transient erythroblastopenia of childhood (0.80 +/- 0.16 U/g Hb) or normal individuals (0.61 +/- 0.13 U/g). These data thus further support that measurement of this purine metabolic enzyme is useful in diagnosing the cause of pure RBC aplasia in children. Of interest, however, elevated RBC-ADA activity also is seen in some children with acute leukaemia and other haematologic disorders. In children with acute lymphoblastic leukaemia (ALL), the increase in RBC-ADA activity is proportional to the degree of anaemia. However, the elevated RBC-ADA activity in this leukaemic population is not related to the fetal haemoglobin concentration. These data suggest increased RBC-ADA activity may be a non specific manifestation of abnormal erythroid stem cell function, an alteration distinct from that seen with reactivation of fetal erythropoiesis. However, since almost all patients with Diamond-Blackfan anaemia manifest elevated RBC-ADA activity, this chemical alteration yet may reflect the specific erythroid differentiation lesion in this disorder. PMID- 3348977 TI - Reversal of drug-resistance in multiple myeloma with verapamil. AB - In vitro testing with a new doxorubicin resistant myeloma cell line revealed the reversal of drug resistance with as little as 100 ng/ml of verapamil (a calcium channel blocker), a dose easily achievable in humans. A first patient with IgG kappa myeloma is presented in whom resistance to VAD (vincristine/doxorubicin infusion plus dexamethasone) chemotherapy was reversed with the administration of verapamil. A subsequent clinical study has been initiated. The potential for further evaluation of calcium channel blockers in multiple myeloma is discussed. PMID- 3348978 TI - Platelet-associated immunoglobulins G, A and M are secreted during platelet activation: normal levels but defective secretion in grey platelet syndrome. AB - Platelet-associated (PA) IgG is known to be released from normal human platelets when they are stimulated by aggregating agents. We have studied whether PA-IgA and PA-IgM are also secreted during platelet activation or during blood collection and processing and whether their levels are related to those in serum. Processing of platelets from normal donors in the presence of secretion inhibitors prostaglandin E1 (PGE1) and theophylline increased levels of both surface and total PA-immunoglobulins (Ig) in intact and lysed platelets respectively, with increases being significant for surface PA-IgA and PA-IgM and total PA-IgM. About 50% of total PA-IgM, 40% PA-IgA and 20% PA-IgG was detectable on intact platelets. All three PA-Ig and PA-albumin were secreted in response to thrombin and this release was inhibited by PGE1. The platelet:serum ratio of each Ig and albumin were similar. In grey platelets deficient in alpha-granules, PA-Ig and PA-albumin levels were raised per platelet but when increased platelet size was taken into account PA-Ig were normal and PA-albumin just below normal. Although thrombin caused release of most of the small amounts of beta thromboglobulin present, PA-Ig and PA-albumin were not released. This suggests that PA-Ig and albumin from plasma may enter a pool of secretory proteins in normal platelets, but in grey platelets they remain in some other site. PMID- 3348979 TI - Two different theta (theta) globin gene deletions observed among black newborn babies. AB - Two different theta 1 globin gene deletions have been detected in the Black population of the southeastern U.S.A. Restriction mapping of the alpha globin gene cluster indicated that one deletion removes approximately 1.8 kb of DNA including most of the theta 1 globin gene, while the second removes approximately 6 kb of DNA including the entire theta 1 globin gene. These defects do not cause haematological alterations in the newborn or in the adult (established for the smaller deletion only), nor were changes observed in polypeptide chain patterns at birth. PMID- 3348980 TI - The role of glutathione peroxidase in the anti-oxidant system of erythrocytes. PMID- 3348981 TI - Alpha-thalassaemia in an Asian Indian. PMID- 3348982 TI - Ectopic production of calcitonin and hypocalcaemia in acute leukaemia. PMID- 3348983 TI - Thrombopoietic inhibitory activity in serum of patients with refractory anaemia. PMID- 3348984 TI - HLA antigens and thrombocytopenia in HIV seropositive subjects. PMID- 3348985 TI - Anticardiolipin antibodies in HIV infected patients with or without immune thrombocytopenic purpura. PMID- 3348986 TI - Antiphospholipid antibodies in haemophiliacs. PMID- 3348987 TI - Functional assessment scale: a visual graph of nursing assessment. PMID- 3348988 TI - Post-lumbar puncture headache: review of the literature and nursing implications. PMID- 3348989 TI - Occupational health for health workers. PMID- 3348990 TI - Variation in hospital morbidity in the male workforce of Western Australia. AB - The associations of hospital morbidity with occupation were studied in Western Australian men of working age in 1981-2. Data on hospital morbidity were derived from a population based system that covered all short stays in hospitals in the state. Occupations were grouped into 12 major categories and conditions were coded using the International Classification of Diseases. Armed services personnel had the highest overall rate of hospital admissions, followed by transport and communications workers and by administrative and managerial workers. Injuries were the most common cause of referral to hospital. Four occupational groups, farmers and allied workers, miners and quarrymen, transport and communications workers, and craftsmen, production workers, and labourers were often associated with injury. Diseases of the musculoskeletal system and connective tissue were the second most common cause for referral and were increased in transport and communications workers, and in craftsmen, production workers, and labourers. Several other associations between causes of hospital admission and major occupational groups were observed, including associations of circulatory system diseases with professional and technical work and with administrative and managerial work. The excess of hospital admissions due to factors associated with occupation was estimated to be 12,665 admissions a year or 24.9% of the total in working men. PMID- 3348991 TI - Fetal death and work in pregnancy. AB - The relation between spontaneous abortion (n = 5010), stillbirth without congenital defect (n = 210), and working conditions was analysed in 22,613 previous pregnancies of 56,067 women interviewed, 1982-4, immediately after termination of their most recent (current) pregnancy. The 22,613 previous pregnancies were those in which at time of conception the women were employed 30 or more hours a week. Ratios of observed (O) to expected (E) fetal deaths after allowance by logistic regression for seven non-occupational confounding variables were calculated at four stages of pregnancy in 60 occupational groups and six main sectors for women whose work entailed various physical demands, environmental conditions, and exposure to chemicals. The O/E ratios for abortion were raised in the sales sector (1.13, p less than 0.05) and services sector (1.11, p less than 0.01) and for stillbirth in the sales sector (1.50, p less than 0.1). Substantially increased O/E ratios for late but not early abortion were found in operating room nurses (2.92, p less than 0.05), radiology technicians (3.82, p less than 0.01), and employees in agriculture and horticulture (2.40, p less than 0.05); in all categories the O/E ratio for stillbirth were also raised but only significantly (5.55, p less than 0.01) in the latter group. The O/E ratio for stillbirth was also raised in leather manufacture (3.09, p less than 0.01). In both individual and grouped analysis (the latter undertaken to minimise the possible effect of recall bias) significantly increased O/E ratios for abortion were found in women exposed to various high levels of physical stress, particularly weight lifting, other physical effort, and standing (p less than 0.01). Increased ratios for stillbirth at this level of significance (p less than 0.01) were found for other physical effort and vibration. Noteworthy chemical exposure was identified only in the health, services, and manufacturing sectors; the O/E ratio for stillbirth approached two in women exposed to solvents, almost all in manufacturing (p less than 0.01). In the latter sector exposed to solvents was also associated with an approximately 20% increase in abortion ratio at similar probability level. PMID- 3348992 TI - Odds ratios of work related deaths in United States workers. AB - A new data set on job related mortality within 347 3 digit occupations is merged with two national probability samples of United States workers to assess which groups are in hazardous and which in safe jobs. Logistic regressions are fitted to the two samples and the following covariates are assumed to explain employment in a hazardous job: age, race, gender, schooling, region, and marital status. Results from both samples are remarkably similar. Odds ratios for non-whites versus whites are roughly 1.2/1; for high school dropouts versus people with some college education roughly 2.2/1; and for men versus women roughly 5.0/1. PMID- 3348993 TI - In vivo tibia lead measurements as an index of cumulative exposure in occupationally exposed subjects. AB - In vivo tibia lead measurements of 20 non-occupationally exposed and 190 occupationally exposed people drawn from three factories were made using a non invasive x ray fluorescence technique in which characteristic x rays from lead are excited by gamma rays from a cadmium-109 source. The maximum skin dose to a small region of the shin was 0.45 mSv. The relation between tibia lead and blood lead was weak in workers from one factory (r = 0.11, p greater than 0.6) and among the non-occupationally exposed subjects (r = 0.07, p greater than 0.7); however, a stronger relation was observed in the other two factories (r = 0.45, p less than 0.0001 and r = 0.53, p less than 0.0001). Correlation coefficients between tibia lead and duration of employment were consistently higher at all three factories respectively (r = 0.86, p less than 0.0001; r = 0.61, p less than 0.0001; r = 0.80, p less than 0.0001). A strong relation was observed between tibia lead and a simple, time integrated, blood lead index among workers from the two factories from which blood lead histories were available. The regression equation from two groups of workers (n = 88, 79) did not significantly differ despite different exposure conditions. The correlation coefficient for the combined data set (n = 167) was 0.84 (p less than 0.0001). This shows clearly that tibia lead, measured in vivo by x-ray fluorescence, provides a good indicator of long term exposure to lead as assessed by a cumulative blood lead index. PMID- 3348994 TI - Malignant mesothelioma in a cohort of asbestos insulation workers: clinical presentation, diagnosis, and causes of death. AB - Malignant mesothelioma has been rare in the general population. In recent decades its incidence has risen dramatically, parallel to the increasing use of asbestos in industry since 1930. Altogether 17,800 asbestos insulation workers, members of the International Association of Heat and Frost Insulators and Asbestos Workers (AFL-CIO-CLC) in the United States and Canada, were enrolled for prospective study on 1 January 1967 and followed up to the present. Every death that occurs is investigated by our laboratory. One hundred and seventy five deaths from mesothelioma occurred among the 2221 men who died in 1967-76 and 181 more such deaths in the next eight years. Altogether, 356 workers had died of malignant mesothelioma (pleural or peritoneal) by 1984. Diagnosis of mesothelioma was accepted only after all available clinical, radiological, and pathological material was reviewed by our laboratory and histopathological confirmation by the pathology unit made in each case. One hundred and thirty four workers died of pleural and 222 of peritoneal mesothelioma. Age at onset of exposure, age at onset of the disease, and age at death were similar in both groups of patients. Significant difference was noted only in the time elapsed from onset of exposure to the development of first symptoms, which was longer in the group with peritoneal mesothelioma. Shortness of breath, either new or recently increased, and chest pain were the most frequent presenting symptoms in the group with pleural mesothelioma; abdominal pain and distension were frequent in the patients with peritoneal mesothelioma. Pleural effusion or ascites were found in most patients. The most effective approach to the diagnosis of malignant pleural mesothelioma in these cases was by open lung biopsy; exploratory laparotomy was best for diagnosing peritoneal mesothelioma. Patients with pleural mesothelioma died principally from pulmonary insufficiency whereas those with peritoneal mesothelioma succumbed after a period of pronounced wasting. PMID- 3348995 TI - Paternal employment in solvent related occupations and adverse pregnancy outcomes. AB - Washington State birth certificates were examined for associations between adverse pregnancy outcomes and paternal employment in solvent exposed occupations. Four cohorts defined by live, singleton births to fathers usually employed as auto body shop workers, painters (construction and maintenance), printers, or fibreglass workers were compared retrospectively with both a systematically selected control cohort and a low solvent exposed, occupationally defined control cohort (paternal electricians). The effects of maternal race and medical illness were controlled by sample restriction; maternal age and gravidity by stratified analysis. There was evidence of increased risk of low birth weight for infants born to fathers employed as body shop workers (relative risk = 1.6; 95% confidence interval = 1.1-2.4) or painters (RR = 1.4; CI = 0.9-2.1) when compared with the systematically selected controls but not with the electrician controls. The excess risk appeared stronger when only term infants were analysed suggesting a mechanism of growth retardation rather than prematurity. There was no evidence of increased risk among the other exposed cohorts or for other adverse pregnancy outcomes. Several design features limit the interpretation of the findings and confirmation by other studies is needed. PMID- 3348996 TI - Skin telangiectases and ischaemic disorders in primary aluminium production workers. PMID- 3348997 TI - Risk assessment in the asbestos cement industry. PMID- 3348998 TI - Asbestos related lung disease in maintenance workers. PMID- 3348999 TI - Investigating dose response relations on occupational mortality studies. PMID- 3349000 TI - Failed sterilization and the law. PMID- 3349001 TI - Magnesium supplementation in pregnancy. A double-blind study. AB - The effect of magnesium supplementation in pregnancy was studied in 568 women who were treated with 15 mmol magnesium-aspartate-hydrochloride per day or aspartic acid as placebo given orally during pregnancy from less than or equal to 16 weeks. Allocation to the two groups was performed according to the women's birthdates. Magnesium supplementation during pregnancy was associated with significantly fewer maternal hospitalizations, a reduction in preterm delivery, and less frequent referral of the newborn to the neonatal intensive care unit. The results suggest that magnesium supplementation during pregnancy has a significant influence on fetal and maternal morbidity both before and after delivery. PMID- 3349002 TI - The effect of the antiprogestin RU 486 on uterine contractility and sensitivity to prostaglandin and oxytocin. AB - The effect of RU 486, a steroid acting as an antiprogestin at the receptor level, on uterine contractility and sensitivity to the prostaglandin analogue, 16 phenoxy-PGE2 methyl sulfonylamide (16-phenoxy-PGE2) and to oxytocin was studied in 29 women in early pregnancy. Seven untreated women at the same stage of pregnancy served as controls. In the untreated women no spontaneous uterine contractility was recorded and the response to 0.25 mg 16-phenoxy-PGE2 was characterized by an increase in uterine tonus with superimposed irregular contractions of low amplitude. Treatment with 25 mg RU 486 twice daily resulted in the appearance of regular uterine contractions at 24 h in two out of five patients and in all patients at 36, 48 and 72 h after the start of RU 486 treatment. The withdrawal of progesterone influence changed the inactive early pregnant uterus into an active organ. Administration of 16-phenoxy-PGE2 caused an obvious stimulation of both frequency and amplitude of the contractions. In addition, the significantly increased sensitivity to the prostaglandin analogue, but not to oxytocin, was already apparent 24 h after the start of RU 486 treatment. We have previously shown that the addition of one intramuscular injection of 16-phenoxy-PGE2 on the fourth day of treatment with RU 486 (25 mg twice daily) significantly increased the abortifacient effect of the antiprogestin during early pregnancy. The present study suggests that a shorter treatment may be possible. PMID- 3349003 TI - The effect of vaginal delivery on the urethral sphincter. AB - To investigate the aetiological role of vaginal delivery in genuine stress incontinence we compared two groups of women who underwent full urodynamic assessment in our department. The women in the first group had competent urethral sphincter mechanisms and those in the second group had genuine stress incontinence. There were no differences between the two groups in respect of parity, number of vaginal deliveries or birthweight of the heaviest baby. The group with competent urethral sphincter mechanisms did show some evidence to implicate an increased number of vaginal deliveries in poor function of the distal part of the urethral sphincter mechanism. PMID- 3349004 TI - Correlation of urethral physiology and skin collagen in postmenopausal women. AB - Connective tissue collagen is thought to contribute to the generation of urethral pressure. It has been previously shown that skin collagen and urethral pressure are oestrogen dependent. This study demonstrates a correlation between urethral pressure measurements and skin collagen content. It is suggested that the beneficial effect of oestrogens on urethral function may be mediated by collagen. PMID- 3349005 TI - Clinical features of women with chronic lower abdominal pain and pelvic congestion. AB - The clinical features of 35 women with pelvic pain and demonstrable congestion on pelvic venography have been characterized by comparing their symptoms and signs with those of 22 women with pelvic pain due to classical pathology. Women with pelvic pain and congestion had a mean age of 32.4 years, were more often multiparous and had had symptoms for 6 months to 20 years. The pain was dull and aching with sharp exacerbations. In individual women it commonly occurred on one side of the abdomen but unlike the pain due to 'classical pathology', it could occur on the other side. The pain was exacerbated by postural changes, and walking. Congestive dysmenorrhoea, deep dyspareunia and postcoital ache were common findings in women with pelvic congestion and 60% had evidence of significant emotional disturbance. The combination of tenderness on abdominal palpation over the ovarian point and a history of postcoital ache was 94% sensitive and 77% specific for discriminating pelvic congestion from other causes of pelvic pain. PMID- 3349006 TI - Fetal death in utero and cocaine abuse. Case report. PMID- 3349007 TI - Maternal posture in second stage and fetal acid base status. PMID- 3349008 TI - In defence of the obstetrician. PMID- 3349009 TI - Ocular and cardiovascular response to topical carteolol 2% and timolol 0.5% in healthy volunteers. AB - Ocular and cardiovascular effects of carteolol 2%, timolol 0.5%, and dummy eyedrops have been measured in a single dose double-blind crossover study in six healthy volunteers. Both drugs lowered intraocular pressure and reduced exercise induced tachycardia. Neither produced a significant change in resting heart rate or blood pressure. The two agents appear comparable as regards ocular hypotensive and cardiovascular effects. PMID- 3349010 TI - Histological appearances of the levator palpebrae superioris muscle in the Marcus Gunn phenomenon. AB - The levator palpebrae superioris muscles from 12 cases of Marcus Gunn phenomenon were examined histologically by means of histochemistry and morphometry. The appearances were of a neurogenic atrophy with pathological changes occurring in both the affected side and the clinically normal side, suggesting that the causative lesion was located in the central nervous system. PMID- 3349011 TI - Why should surgery for early-onset strabismus be postponed? AB - The author presents a continued study of 82 cases of pseudoparalysis of the bilateral rectus muscles in early-onset convergent strabismus following early surgery. Up to 10 years after surgery motor results show that 72% of cases remain within +/- 10 prism dioptres after a single surgical procedure. Sensorial findings corroborate the results of other authors' studies in that binocular association is only achieved in those patients where surgery was carried out at a very young age, not older than 1 year. Surgical procedures consisting of bimedial rectus recession with retroequatorial myopexy are described and the development of alphabetical syndromes and dissociated vertical divergence discussed. The evolution of refraction in these cases is also shown. PMID- 3349012 TI - Visual failure in allergic aspergillus sinusitis: case report. AB - We present a case of rapid progressive unilateral visual loss in a 69-year-old woman who presented with facial pain, ipsilateral proptosis and restriction of eye movements, and nasal symptoms suggestive of sinusitis. A diagnosis of allergic aspergillus sinusitis was made on the basis of local histopathology and systemic features. Over a three-week period vision deteriorated to bare perception of light but showed a dramatic improvement to a level of 6/9 central vision on systemic steroid therapy. The mechanism of visual failure in the context of allergic aspergillus sinusitis and the therapeutic implications are discussed. PMID- 3349013 TI - Malignant melanoma of the choroid in a naevus of Ota. AB - A rare case of choroidal malignant melanoma in a naevus of Ota is described. This is the first reported case from Asia outside the Japanese population. This case illustrates the need for close observation of all pigmented lesions of the eye. PMID- 3349014 TI - Acute angle closure glaucoma precipitated by orbital pseudotumour. AB - A 62-year-old woman presented with acute angle closure glaucoma. After a poor response to conventional treatment the presenting signs were re-evaluated and a diagnosis of pseudotumour of the orbit was made. Treatment with oral steroids resolved both the glaucoma and the orbital pseudotumour. The presumed pathogenesis and literature are reviewed. PMID- 3349015 TI - Changes in astigmatism between the ages of 1 and 4 years: a longitudinal study. AB - Changes in astigmatism during development were studied in 299 infants with astigmatism as they grew from 1 to 4 years of age. All consecutive cases of 1 year-old infants with an astigmatism of 1.0 D or more in at least one eye found at an ophthalmic screening survey were selected for follow-up. The cycloplegic refraction was longitudinally followed at yearly intervals. During development there was no decrease in the degree of hypermetropia, but there was a significant decrease in the incidence and amount of astigmatism during the test period. The most pronounced decrease in magnitude and incidence of astigmatism occurred between the first and second year of life. The majority of astigmatic eyes of the 1-year-old infants had a horizontal curvature greater than the vertical (plus cylinder axis of 180 degrees), and no changes of the axis of the astigmatism were noted during the following years. PMID- 3349018 TI - Ophthalmic survey of a diabetic clinic. PMID- 3349017 TI - Chronic alcoholism and microbial keratitis. AB - In a series of 227 consecutive, non-referred patients with microbial keratitis an analysis of the accumulated hospital records showed that one-third were associated with chronic alcoholism. The diagnosis of alcoholism was usually unsuspected on admission to hospital. The microbial pathogenesis in these patients was distinctive; coagulase-negative staphylococci, alpha- and beta streptococci, moraxellae, enteric Gram-negative bacilli, and polymicrobial infections were unusually prominent. Pseudomonas aeruginosa was uncommon. Trauma, exposure, bullous keratopathy, other external ocular diseases, and self-neglect were the major recognised predisposing causes. The nutritional, toxic and immunological sequelae of alcoholism may also have been contributory. Ophthalmologists should be alert to the diagnosis of chronic alcoholism in their patients. Chronic alcoholism may be an important and underrated risk factor for microbial keratitis. PMID- 3349016 TI - Drug delivery through soft contact lenses. AB - Clinical studies were conducted on 466 patients waiting for senile cataract surgery and receiving chloromycetin, gentamicin, or carbenicillin subconjunctivally and through New Sauflon 70 and New Sauflon 85 lenses. The aqueous drug levels were biologically estimated at various time intervals. Soft contact lenses provided significantly higher drug penetration than subconjunctival therapy. Both modes of treatment provided therapeutically effective levels against most of the common ocular pathogens for varying intervals of 2 to 12 hours. PMID- 3349019 TI - Experimental posterior uveitis. II. Electroretinographic studies. AB - Experimental posterior uveitis was induced by the inoculation of retinal S antigen into black hooded Lister rats. The time course of the disease was monitored by electroretinography (ERG), and the ERG changes were correlated with clinical signs and underlying pathological damage. The ERG became supernormal in the third week after inoculation, with some loss of temporal resolution (lowered ERG flicker fusion frequency), though the disease was not clinically manifest at this time and histological examination was normal. The ERG became subnormal after 21 days as clinical signs of disease began to appear. This subnormality was associated with focal photoreceptor necrosis, the degree of destruction being proportional to the reduction in the ERG. The ERG recovered with resolution of disease in most cases, though return to control values was uncommon. We suggest that the initial supernormal ERG reflects an underlying biochemical change mediated by the action of anti retinal S-antigen antibodies. PMID- 3349020 TI - On the management of retained airgun pellets: a survey of 11 orbital cases. AB - Relevant factors determining the management of inaccessible retained lead airgun pellets are discussed in relation to 11 orbital cases. Although the injuries were of between one month's and 26 years' standing, serum lead levels were normal at under 350 micrograms/l in all instances. This is attributable to the modern alloy composition of the ammunition in question. It is concluded that surgical intervention may be indicated only where there is a mechanical disturbance of ocular motility allied with good visual function. PMID- 3349021 TI - Base pair mismatches and carcinogen-modified bases in DNA: an NMR study of G.T and G.O4meT pairing in dodecanucleotide duplexes. AB - High-resolution two-dimensional NMR studies have been completed on the self complementary d(C-G-C-G-A-G-C-T-T-G-C-G) duplex (designated G.T 12-mer) and the self-complementary d(C-G-C-G-A-G-C-T-O4meT-G-C-G) duplex (designated G.O4meT 12 mer) containing G.T and G.O4meT pairs at identical positions four base pairs in from either end of the duplex. The exchangeable and nonexchangeable proton resonances have been assigned from an analysis of two-dimensional nuclear Overhauser enhancement (NOESY) spectra for the G.T 12-mer and G.O4meT 12-mer duplexes in H2O and D2O solution. The guanosine and thymidine imino protons in the G.T mismatch resonate at 10.57 and 11.98 ppm, respectively, and exhibit a strong NOE between themselves and to imino protons of flanking base pairs in the G.T 12-mer duplex. These results are consistent with wobble pairing at the G.T mismatch site involving two imino proton-carbonyl hydrogen bonds as reported previously [Hare, D. R., Shapiro, L., & Patel, D. J. (1986) Biochemistry 25, 7445 7456]. In contrast, the guanosine imino proton in the G.O4meT pair resonates at 8.67 ppm. The large upfield chemical shift of this proton relative to that of the imino proton resonance of G in the G.T mismatch or in G.C base pairs indicates that hydrogen bonding to O4meT is either very weak or absent. This guanosine imino proton has an NOE to the OCH3 group of O4meT across the pair and NOEs to the imino protons of flanking base pairs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349022 TI - Selective reversible deuteriation of oligodeoxynucleotides: simplification of two dimensional nuclear Overhauser effect NMR spectral assignment of a non-self complementary dodecamer duplex. AB - Oligodeoxynucleotides are reversibly deuteriated at the purine C8 and cytosine C5 positions with deuterioammonium bisulfite at pD 7.8. The exchange reaction is complete after 48 h at 65 degrees C. When an oligomer deuteriated under these conditions is analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy, the purine H8 and cytosine H5 proton signals are selectively removed from the spectrum. A non-self-complementary oligodeoxynucleotide that has been deuteriated in this manner may be annealed with its complement and the resulting heteroduplex analyzed by two-dimensional nuclear Overhauser enhancement (NOESY) spectroscopy. NOE cross-peaks arising from pyrimidine H6-deoxyribose H1' dipolar interactions in both strands are observed, but purine H8-deoxyribose H1' and purine H8 deoxyribose H2',H2" dipolar interactions are only observed for the nondeuteriated strand. The intense cytosine H5-H6 cross-peaks are also removed from the spectrum of the deuteriated strand, which further simplifies interpretation since these strong cross-peaks often interfere with less intense NOE cross-peaks arising from dipolar coupling between purine H8 or pyrimidine H6 and deoxyribose anomeric protons. The resulting spectral simplification allows unambiguous assignments to be made on NOEs that otherwise may be difficult to distinguish. The deuteration procedure is demonstrated with the sequence d(CGTTATAATGCG).d(CGCATTATAACG), which has previously been assigned by traditional NOESY methods [Wemmer, D. E., Chou, S.-H., Hare, D. R., & Reid, B. R. (1984) Biochemistry 23, 2262-2268]. Although the assignment of this dodecadeoxynucleotide may be completed without deuteriation, several NOEs must be assigned indirectly because of degeneracies in the chemical shift of the purine H8 protons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349023 TI - gamma-Aminobutyric acid transport in reconstituted preparations from rat brain: coupled sodium and chloride fluxes. AB - Transport of gamma-aminobutyric acid (GABA) is electrogenic and completely depends on the presence of both sodium and chloride ions. These ions appear to be cotransported with gamma-aminobutyric acid through its transporter [reviewed in Kanner, B. I. (1983) Biochim. Biophys. Acta 726, 293-316]. Using proteoliposomes into which a partially purified gamma-aminobutyric acid transporter preparation was reconstituted, we have been able--for the first time--to provide direct evidence for sodium- and chloride-coupled gamma-aminobutyric acid transport. This has been done by measuring the fluxes of 22Na+, 36Cl-, and [3H]GABA. These fluxes have the following characteristics: There are components of the net fluxes of sodium and chloride that are gamma-aminobutyric acid dependent. The sodium flux is chloride dependent; i.e., when Cl- is replaced by inorganic phosphate or by SO4(2-), gamma-aminobutyric acid dependent sodium fluxes are abolished. The chloride flux is sodium dependent; i.e., when Na+ is replaced by Tris+ or by Li+, gamma-aminobutyric acid dependent chloride fluxes are abolished. Thus, the gamma aminobutyric acid dependent sodium and chloride fluxes appear to be catalyzed by the transporter. Using these fluxes we have attempted to determine the stoichiometry of the process. We measured the initial rate of sodium-dependent gamma-aminobutyric acid fluxes and that of gamma-aminobutyric acid dependent sodium fluxes. This yields the stoichiometry between sodium and gamma aminobutyric acid (2.58 +/- 0.99). Similarly, we measured the stoichiometry between chloride and gamma-aminobutyric acid, which is found to be 1.27 +/- 0.12.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349026 TI - Retinal is not formed in vitro by enzymatic central cleavage of beta-carotene. AB - Rat intestinal mucosa was prepared and incubated with beta-carotene by the procedure of Goodman and Olson [Goodman, DeW. S., & Olson, J.A. (1969) Methods Enzymol. 15, 462-475] to determine beta-carotene cleavage activity. A new detection system for the reaction products of the described enzyme beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) employs solvent extraction of retinoids and carotenoids followed by high-performance liquid chromatography separation and photometric detection of the pigments. It has not detected any newly formed retinal or other retinoids in the intestinal protein preparations from normal or vitamin A deficient rats. The latter were chosen as a possible source of more active enzyme preparations. With corresponding blank samples subjected to identical conditions of incubation but without added protein, small amounts of beta-apocarotenals could be detected. They were previously reported as cleavage products of beta-carotene [Ganguly, J., & Sastry, P.S. (1985) World Rev. Nutr. Diet. 45, 198-220] but are clearly not formed as a result of an enzymatic reaction. The failure to detect in vitro enzymatic central or random cleavage of the beta-carotene molecule in extracts of rat intestinal mucosa emphasizes the need to reevaluate the existing theory of conversion of beta-carotene into vitamin A. PMID- 3349025 TI - Absolute configuration of cis-12-oxophytodienoic acid of flaxseed: implications for the mechanism of biosynthesis from the 13(S)-hydroperoxide of linolenic acid. AB - cis-12-Oxophytodienoic acid (cis-12-oxo-PDA) is a C18 cyclopentenone formed from the 13-(S)-hydroperoxide of linolenic acid in flaxseed and other plant tissues. Although the structure of cis-12-oxo-PDA is well established, the absolute configuration of the side chains has not been determined. We have now measured this important parameter by two independent approaches. The CD spectrum of freshly prepared cis-12-oxo-PDA showed no deviations from base line--implying that the product is racemic. This conclusion was checked by a high-pressure liquid chromatography (HPLC) method capable of resolving the enantiomers; cis-12 oxo-PDA was reduced to two saturated hydroxy analogues which were each converted to (-)-menthoxycarbonyl diastereomers and analyzed by HPLC. Each epimer was resolved as two peaks of equal area, thus confirming that their cis-12-oxo-PDA parent is a racemic mixture, enantiomeric at the ring junctures. We propose that the biosynthesis of racemic cis-12-oxo-PDA proceeds by dehydration of the 13(S) hydroperoxide to an allene oxide. A major fate of the allene oxide is hydrolysis to an alpha-ketol, which is always formed together with cis-12-oxo-PDA. The allene oxide also opens to a zwitterion, which undergoes charge delocalization to form a planar intermediate; this structure is the achiral precursor of the stable end product of pericyclic ring closure, viz., racemic cis-12-oxo-PDA. PMID- 3349024 TI - Sequential 1H NMR assignments and secondary structure of hen egg white lysozyme in solution. AB - Assignments for 1H NMR resonances of 121 of the 129 residues of hen egg white lysozyme have been obtained by sequence-specific methods. Spin systems were identified with phase-sensitive two-dimensional (2-D) correlated spectroscopy and single and double relayed coherence transfer spectroscopy. For key types of amino acid residues, particularly alanine, threonine, valine, and glycine, complete spin systems were identified. For other residues a less complete definition of the spin system was found to be adequate for the purpose of sequential assignment. Sequence-specific assignments were achieved by phase-sensitive 2-D nuclear Overhauser enhancement spectroscopy (NOESY). Exploitation of the wide range of hydrogen exchange rates found in lysozyme was a useful approach to overcoming the problem of spectral overlap. The sequential assignment was built up from 21 peptide segments ranging in length from 2 to 13 residues. The NOESY spectra were also used to provide information about the secondary structure of the protein in solution. Three helical regions and two regions of beta-sheet were identified from the NOESY data; these regions are identical with those found in the X-ray structure of hen lysozyme. Slowly exchanging amides are generally correlated with hydrogen bonding identified in the X-ray structure; a number of exceptions to this general trend were, however, found. The results presented in this paper indicate that highly detailed information can be obtained from 2-D NMR spectra of a protein that is significantly larger than those studied previously. PMID- 3349027 TI - Enzymatically active angiogenin/ribonuclease A hybrids formed by peptide interchange. AB - The primary structures of the blood vessel inducing protein human angiogenin and human pancreatic ribonuclease (RNase) are 35% identical. Angiogenin catalyzes the limited cleavage of ribosomal RNA (18 and 28 S), yielding a characteristic pattern of polynucleotide products, but shows no significant activity toward conventional pancreatic RNase substrates [Shapiro, R., Riordan, J. F., & Vallee, B. L. (1986) Biochemistry 25, 3527-3532]. Angiogenin/RNase hybrid enzymes- wherein particular regions of primary structure in RNase are replaced by the corresponding segments of angiogenin--serve to explore the structural features underlying angiogenin's characteristic activities. Herein we show that synthetic angiogenin peptides, Ang(1-21) and Ang(108-123), form noncovalent complexes with inactive fragments of bovine RNase A--RNase(21-124) (i.e., S-protein) and RNase(1 118), respectively--with regeneration of activity toward conventional RNase substrates. Maximal activities for the Ang(1-21)/S-protein complex (Kd = 1.0 microM) are 52%, 45%, and 15% toward cytidine cyclic 2',3'-phosphate, cytidylyl(3'----5')adenosine, and yeast RNA, respectively. In contrast, activities of the RNase(1-118)/Ang(108-123) hybrid (Kd = 25 microM) are 1-2 orders of magnitude lower toward cyclic nucleotides and dinucleoside phosphates. However, substitution of phenylalanine for Leu-115 in Ang(108-123) increases activity up to 100-fold. Both His-13 and His-114 in the angiogenin peptides are required for activity since their substitution by alanine yields inactive complexes. Importantly, the pattern of polynucleotide products formed during cleavage of ribosomal RNA by the Ang(1-21)/S-protein hybrid shows a striking resemblance to that formed by angiogenin, demonstrating that the hybrid retains features of both angiogenin and RNase A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349028 TI - Purification and characterization of human salivary peroxidase. AB - Human salivary peroxidase (SPO) has been purified to homogeneity by subjecting human parotid saliva to immunoaffinity, cation exchange, and affinity chromatography. These procedures resulted in a 992-fold purification of the enzyme. When purified SPO was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), three Coomassie stainable bands were apparent, all of which stained positive for enzyme activity. The apparent molecular weights of the three bands were 78,000, 80,000, and 280,000 as analyzed by SDS-PAGE. Reduction with 2-mercaptoethanol resulted in a decreased mobility of these bands, and enzyme activity could no longer be detected on the gels. The SPO preparation had the characteristic peroxidase heme spectrum in the range 405-420 nm. The ratio between the absorbance of the Soret band (412 nm) and the absorbance at 280 nm was 0.81. The enzyme activity was inhibited by the classical peroxidase inhibitors cyanide and azide. Salivary peroxidase is similar to bovine lactoperoxidase (LPO) in amino acid composition, in ultraviolet and visible spectrum, in reaction with cyanide, in susceptibility to 2-mercaptoethanol inactivation, and in thermal stability. The two enzymes differ in carbohydrate composition and content. SPO contains 4.6% and LPO 7% total neutral sugars. The ratio of glucosamine to galactosamine is 2:1 in SPO and 3:1 in LPO. SPO contains mannose, fucose, and galactose in a molar ratio of 1.5:1.5:1.0, while the ratio was 14.9:0.5:1.0 in LPO. Glucose was present in both preparations in minor amounts. The concentration of azide required for 50% inhibition of enzyme activity was 20-fold greater for LPO than for SPO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349030 TI - Conformational states of N-acylalanine dithio esters: correlation of resonance Raman spectra with structures. AB - The conformational states of N-acylalanine dithio esters, involving rotational isomers about the RC(=O)NH--CH(CH3) and NHCH(CH3)--C(=S) bonds, are defined and compared to those of N-acylglycine dithio esters. The structure of N-(p nitrobenzoyl)-DL-alanine ethyl dithio ester has been determined by X-ray crystallographic analysis; it is a B-type conformer with the amide N atom cis to the thiol sulfur. Raman and resonance Raman (RR) measurements on this compound and for the B conformers of solid N-benzoyl-DL-alanine ethyl dithio ester and N (beta-phenylpropionyl)-DL-alanine ethyl dithio ester and its NHCH(CD3)C(=S) and NHCH(CH3)13C(=S) analogues are used to set up a library of RR data for alanine based dithio esters in a B-conformer state. (Methyloxycarbonyl)-L-phenylalanyl-L alanine ethyl dithio ester crystallizes in an A-like conformational state wherein the alanine N atom is nearly cis to the thiono S atom (C=S) [Varughese, K.I., Angus, R.H., Carey, P.R., Lee, H., & Storer, A.C. (1986) Can. J. Chem. 64, 1668 1673]. RR data for this solid material in its isotopically unsubstituted and CH(C D3)C(=S) and CH(CH3)13C(=S) forms provide information on the RR signatures of alanine dithio esters in A-like conformations. RR spectra are compared for the solid compounds, for N-(p-nitrobenzoyl)-DL-alanine, N-(beta-phenylpropionyl)-DL alanine, and (methyloxycarbonyl)-L-phenylalanyl-DL-alanine ethyl dithio esters, and for several 13C=S- and CD3-substituted analogues in CCl4 or aqueous solutions. The RR data demonstrate that the alanine-based dithio esters take up A, B, and C5 conformations in solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349029 TI - Steady-state kinetics of thiocyanate oxidation catalyzed by human salivary peroxidase. AB - A steady-state kinetic analysis was made of thiocyanate (SCN-) oxidation catalyzed by human peroxidase (SPO) isolated from parotid saliva. For comparative purposes, bovine lactoperoxidase (LPO) was also studied. Both enzymes followed the classical Theorell-Chance mechanism under the initial conditions [H2O2] less than 0.2mM, [SCN-] less than 10mM, and pH greater than 6.0. The pH-independent rate constants (k1) for the formation of compound I were estimated to be 8 X 10(6) M-1 s-1 (SD = 1, n = 18) for LPO and 5 X 10(6) M-1 s-1 (SD = 1, n = 11) for SPO. The pH-independent second-order rate constants (k4) for the oxidation of thiocyanate by compound I were estimated to be 5 X 10(6) M-1 s-1 (SD = 1, n = 18) for LPO and 9 X 10(6) M-1 s-1 (SD = 2, n = 11) for SPO. Both enzymes were inhibited by SCN- at pH less than 6. The pH-independent equilibrium constant (Ki) for the formation of the inhibited enzyme-SCN- complex was estimated to be 24 M-1 (SD = 12, n = 8) for LPO and 44 M-1 (SD = 4, n = 10) for SPO. An apparent pH dependence of the estimated values for k4 and Ki for both LPO and SPO was consistent with a mechanism based on assumptions that protonation of compound I was necessary for the SCN- peroxidation step, that a second protonation of compound I gave an inactive form, and that the inhibited enzyme-SCN- complex could be further protonated to give another inactive form.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349031 TI - Conformational variability in an enzyme's active site: resonance Raman evidence for different acyl group conformations in N-acylglycine and N-acylalanine dithioacyl papains. AB - It is demonstrated that the vibrational modes associated with the catalytically labile region of N-acylalanine dithioacyl papains undergo a major reorganization compared to the normal modes of corresponding model compounds. Thus, the resonance Raman (RR) spectrum of, e.g., N-benzoylalanine dithioacyl papain and its response to isotopic labeling cannot be understood completely on the basis of the RR spectrum of N-benzoylalanine ethyl dithio ester in one of its known conformational states [detailed in Lee, H., Angus, R. H., Storer, A. C., Varughese, K. I., & Carey, P. R. (1988) Biochemistry (preceding paper in this issue)]. This situation contrasts sharply to that for N-acylglycine dithioacyl papains whose RR spectra closely resemble those of the corresponding N acylglycine ethyl dithio esters in a conformational state known as conformer B. For the N-acylalanine intermediates two possible causes are put forward to explain the rearrangement of the normal modes. First, the acyl groups based on alanine may bind in papain's active site in a conformation whose torsional angles near the -C(=S)S-group differ markedly from those of characterized model compounds. The second, and presently favored, explanation is that the N acylalanine moiety is binding in the active site in an A- or C5-like conformation and that, in addition, there is significant vibrational coupling between some of the normal modes of the bound substrate and the normal modes associated with parts of the enzyme in contact with the substrate. The finding that deacylation for N-acylglycine or N-acylalanine dithioacyl papains must proceed from structures which are different is an indication that the mechanism of deacylation may not have strict stereochemical requirements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349032 TI - Comparison of the kinetics of the papain-catalyzed hydrolysis of glycine- and alanine-based esters and thiono esters. AB - The kinetic constants for the papain-catalyzed hydrolysis of a series of substrates with glycine or alanine in the P1 position are discussed. The substrates have N-benzoyl, N-(p-nitrobenzoyl), N-(beta-phenylpropionyl), or N (methyloxycarbonyl)phenylalanine attached to the P1 moiety, and kinetic constants are obtained for both esters and thiono esters. The results for the hydrolysis of esters can be readily interpreted in terms of the known specificity of papain. For any glycine ester the change in kcat/Km upon substituting C=S for C=O or upon substituting an alpha-CH3 group is minimal. However, upon making both these substitutions, i.e., going from a glycine ester to an alanine thiono ester substrate, larger changes are seen for this ratio. Data for N-benzoyl- and N (beta-phenylpropionyl)glycine and -alanine methyl thiono esters show that k2 is the parameter most affected by the double C=S and alpha-CH3 substitution. A further conclusion is that the deacylation rate constants for any pair of glycine and alanine dithioacyl papains are similar; e.g., for the intermediates based on the "good" substrates PheAla and PheGly k3 differs by only 20%. This is a surprising finding in light of the very different conformations and interactions of the bound acyl groups revealed by resonance Raman spectroscopy and raises the possibility that specific stereochemical effects, such as the oxyanion hole and general base catalysis, are not operating in the hydrolysis of dithioacyl papains. PMID- 3349033 TI - Equilibrium studies on the binding of cadmium(II) to human serum transferrin. AB - The binding of cadmium(II) to human serum transferrin in 0.01 M N-(2 hydroxyethyl)-piperazine-N'-2-ethanesulfonic acid with 5 mM bicarbonate at 25 degrees C has been evaluated by difference ultraviolet spectroscopy. Equilibrium constants were determined by competition versus three different low molecular weight chelating agents: nitrilotriacetic acid, ethylenediamine-N,N'-diacetic acid, and triethylenetetramine. Conditional equilibrium constants for the sequential binding of two cadmium ions to transferrin under the stated experimental conditions are log K1 = 5.95 +/- 0.10 and log K2 = 4.86 +/- 0.13. A linear free energy relationship for the complexation of cadmium and zinc has been prepared by using equilibrium data on 243 complexes of these metal ions with low molecular weight ligands. The transferrin binding constants for cadmium and zinc are in good agreement with this linear free energy relationship. This indicates that the larger size of the cadmium(II) ion does not significantly hinder its binding to the protein. PMID- 3349034 TI - Intermediates in the refolding of ribonuclease at subzero temperatures. 1. Monitoring by nitrotyrosine absorbance. AB - Derivatives of ribonuclease A in which tyrosines-73, -76, and -115 were nitrated have been synthesized, purified to homogeneity, and characterized by NMR, isoelectric points, absorbance spectra, and catalytic activity. The positions of their reversible thermal unfolding transitions were determined in 35% methanol at pH* 3.0 and 6.0. In the present study the kinetics of the refolding of these nitrotyrosine derivatives were measured at -15 degrees C at pH* 3.0 and 6.0 by using a cryosolvent composed of 35% aqueous methanol. The rates of folding of different regions of the molecule were determined by using the nitrotyrosines as environmentally sensitive probes. Multiphasic kinetics were observed for the refolding of the nitro-Tyr-115, -73, and -76 derivatives. The native environment about Tyr-115 was formed more rapidly than that about Tyr-73 and -76, and the native environment about both these tyrosines was attained much sooner than the native state itself, as judged by other probes. The results indicate that different regions of the molecule attain their native environments at different rates. This observation shows that the folding pathway must involve partially folded intermediate states. PMID- 3349035 TI - Intermediates in the refolding of ribonuclease at subzero temperatures. 3. Multiple folding pathways. AB - The kinetics of refolding of ribonuclease A have been measured at -15 degrees C by monitoring the intrinsic fluorescence and absorbance signals from the six tyrosine residues. For each probe multiphasic kinetics were observed. The burial of tyrosine residues, as determined by the change in absorbance at 286 nm, revealed four phases, whereas the kinetics of refolding monitored by fluorescence revealed only two phases. The rates of the transients detected by fluorescence were independent of pH. One of the faster transients detected by delta A286 involved a decrease in absorbance, which is consistent with solvent exposure, rather than burial, and suggests the possibility of an abortive partially folded intermediate in the earlier stages of folding. Double-jump unfolding assays were used to follow the buildup and decay of an intermediate in the refolding reaction at -15 degrees C. At both pH* 3.0 and pH* 6.0 the maximum concentration of the intermediate was 25-30% of the total protein. The existence of a second pathway of slow folding was inferred from the difference in rate of formation of native enzyme and breakdown of the observed intermediate, and by computer simulations. In addition, the unfolding assay demonstrated that 20% of the unfolded protein was converted to native at a much faster rate, consistent with observations in aqueous solution that 80% of unfolded ribonuclease A consists of slow-folding species. Kinetics and amplitude data from these and other refolding experiments with different probes were used to develop possible models for the pathway of refolding. The simplest system consistent with the results for the slow-refolding species involves two parallel pathways with multiple intermediates on each of them. Several independent lines of evidence indicate that about 30% of the unfolded state refolds by the minor pathway, in which the slowest observed phase is attributed to the isomerization of Pro-93. The major pathway involves 50% of the unfolded state; the reason why it refolds slowly is not apparent. A native like intermediate is formed considerably more rapidly in the major slow-refolding pathway, compared to the minor pathway. PMID- 3349037 TI - Translational control in early sea urchin embryogenesis: initiation factor eIF4F stimulates protein synthesis in lysates from unfertilized eggs of Strongylocentrotus purpuratus. AB - We have used cell-free translation systems from unfertilized eggs and embryos of the sea urchin Strongylocentrotus purpuratus to analyze the mechanisms limiting protein synthesis in early embryogenesis. Unfertilized egg lysates supplemented with nuclease-treated reticulocyte lysate were stimulated 2-4-fold in incorporation of radioactive amino acid into protein. Thirty-minute zygote lysates supplemented in this way were not stimulated. These results suggested that a component limiting translation in the unfertilized egg lysate was provided by the nuclease-treated lysate and that this component was no longer limiting protein synthesis following fertilization. In view of these results, partially fractionated lysates and individual purified translational components from mammalian cells were tested for stimulation of the unfertilized egg lysate. A 1000000g supernatant devoid of ribosomal subunits also stimulated the unfertilized egg lysate. Thus, the stimulation was not due to the addition of active ribosomal subunits but to soluble elements in the reticulocyte lysate. Of the soluble components tested, only the cap-binding protein complex eIF4F caused a dramatic stimulation of the unfertilized egg lysate (2-3.5-fold). The 30-min zygote lysate was not stimulated by eIF4F or by any of the other components tested, supporting the hypothesis that a block in the translational machinery is removed at fertilization. A rabbit reticulocyte shift assay was used to analyze whether mRNA is limiting in early development. When unfertilized egg lysate was added to the shift assay, there was no shift in radioactivity from 43S to 80S complexes, indicating the unfertilized egg mRNA is not available for translation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349036 TI - Growth hormone promoted tyrosyl phosphorylation of growth hormone receptors in murine 3T3-F442A fibroblasts and adipocytes. AB - Because many growth factor receptors are ligand-activated tyrosine protein kinases, the possibility that growth hormone (GH), a hormone implicated in human growth, promotes tyrosyl phosphorylation of its receptor was investigated. 125I Labeled human GH was covalently cross-linked to receptors in intact 3T3-F442A fibroblasts, a cell line which differentiates into adipocytes in response to GH. The cross-linked cells were solubilized and passed over a column of phosphotyrosyl binding antibody immobilized on protein A-Sepharose. Immunoadsorbed proteins were eluted with a hapten (p-nitrophenyl phosphate) and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The eluate from the antibody column contained an Mr 134,000 125I GH-receptor complex. A similar result was obtained when the adipocyte form of 3T3 F442A cells was used in place of the fibroblast form. O-Phosphotyrosine prevented 125I-GH-receptor complexes from binding to the antibody column, whereas O phosphoserine and O-phosphothreonine did not. In studies of GH-promoted phosphorylation in 3T3-F442A fibroblasts labeled metabolically with [32P]Pi, GH was shown to stimulate formation of a 32P-labeled protein which bound to immobilized phosphotyrosyl binding antibodies. The molecular weight of 114,000 obtained for this protein is similar to that expected for non-cross-linked GH receptor. The Mr 114,000 phosphorylated protein could be immunoprecipitated with anti-GH antibody, indicating that GH remained noncovalently bound to this protein during absorption to and elution from the immobilized phosphotyrosyl binding antibody. Phosphoamino acid analysis after both limited acid hydrolysis and extensive base hydrolysis of the Mr 114,000 phosphoprotein confirmed the presence of phosphotyrosyl residues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349038 TI - Sulfhydryl group content of chicken progesterone receptor: effect of oxidation on DNA binding activity. AB - DNA binding activity of chicken progesterone receptor B form (PRB) and A form (PRA) has been examined. This activity is strongly dependent upon the presence of thiols in the buffer. Stability studies showed that PRB was more sensitive to oxidation than was PRA. Receptor preparations were fractionated by DNA-cellulose chromatography to DNA-positive and DNA-negative subpopulations, and sulfhydryl groups were quantified on immunopurified receptor by labeling with [3H]-N ethylmaleimide. Labeling of DNA-negative receptors with [3H]-N-ethylmaleimide showed 21-23 sulfhydryl groups on either PRA or PRB form when the proteins were reduced and denatured. A similar number was seen without reduction if denatured DNA-positive receptor species were tested. In contrast, the DNA-negative PRB had only 10-12 sulfhydryl groups detectable without reduction. A similar number (12 13 sulfhydryl groups) was found for PRA species that lost DNA binding activity after exposure to a nonreducing environment in vitro. We concluded that the naturally occurring receptor forms unable to bind to DNA, as well as receptor forms that have lost DNA binding activity due to exposure to a nonreducing environment in vitro, contain 10-12 oxidized cysteine residues, likely present as disulfide bonds. Since we were unable to reduce the disulfide bonds when the native DNA-negative receptor proteins were treated with dithiothreitol (DTT), we speculate that irreversible loss of DNA binding activity of receptor in vitro is due to oxidation of cysteine residues that are not accessible to DTT in the native state. PMID- 3349039 TI - Fluorescent probes of electrostatic potential 1 nm from the membrane surface. AB - We measured the electrostatic potential 1 nm from the surface of charged phospholipid bilayer membranes to test the predictions of the Gouy-Chapman theory. Fluorescent probes (anthraniloyl, 5-(dimethylamino)naphthalene-1 sulfonyl, Lucifer yellow) were attached covalently to the sialic acid residue of the ganglioside galactosyl-N-acetylgalactosaminyl(N acetylneuraminyl)galactosylglucosylc eramide (GM1). These fluorescent gangliosides were incorporated into neutral [phosphatidylcholine (PC)] or charged [phosphatidylserine (PS)] phospholipid bilayers, and the fluorescence was quenched with the cations thallium and 4-amino-2,2,6,6-tetramethylpiperidine-1 oxyl (tempamine). We calculated the electrostatic potential at the chromophore from the quenching ratio using the Boltzmann relation: the average potential was 30 mV for PS bilayers in 0.1 M NaNO3. We assume the chromophore is 1 nm from the surface because X-ray diffraction measurements demonstrate that the sialic acid residue of GM1 is 1 nm from the surface of a PC/GM1 bilayer [McDaniel, R. V., & McIntosh, T. J. (1986) Biophys. J. 49, 94-96]. We also used thallium and tempamine to quench the fluorescence of chromophores located at the surface of the PS membranes; in 0.1 M NaNO3 the average surface potential was -80 mV, which agrees with other measurements. The Gouy-Chapman theory predicts that the potential 1 nm from a membrane with a surface potential of -80 mV is -24 mV; this prediction agrees qualitatively with the experimental results obtained with fluorescent gangliosides. PMID- 3349040 TI - Asymmetry of lysophosphatidylcholine/cholesterol vesicles is sensitive to cholesterol modulation. AB - Sonication of lysophosphatidylcholine (lysoPC; 20 mumol/mL) and cholesterol (chol) in aqueous medium produces lamellar structures over a wide range of concentrations. From 25 to 47 mol % cholesterol, electron microscopy (EM) after negative staining showed extended stacklike lamellae about 40 A thick. From 50 to 60 mol % chol, freeze-fracture EM showed homogeneous populations of small unilamellar vesicles averaging 260-310 A in diameter. Phosphorus-31 nuclear magnetic resonance was used to characterize the stacklike lamellae and to measure the distribution of the lysophospholipid between the outer and inner leaflet of the vesicles as a function of sterol concentration. We found that in lysoPC/chol dispersions containing less than equimolar amounts of cholesterol (25-47 mol %), the entire phosphorus signal (40.5 ppm) was shifted downfield by 10.5 ppm upon addition of Pr3+ (2.4 mM), consistent with the stacklike lamellar structures in which all lysoPC head groups are accessible to the ions. By contrast, addition of Pr3+ to lysoPC/chol vesicles containing equimolar or higher amounts of cholesterol (up to 60 mol %) gave rise to two phosphorus peaks. The more intense downfield signal (51.0 ppm) responsive to paramagnetic ions was assigned to lysoPC located in the outer vesicle leaflet. The upfield signal (40.5 ppm), which was not affected by the ions, was assigned to inside lysoPC. For lysoPC/chol (1:1) vesicles, an outside to inside lysophospholipid ratio (Ro/i) of 6.5 was determined. Essentially the same Ro/i value (6.7) was obtained on lysoPC/chol (1:1) vesicles which after dialysis contained only entrapped Pr3+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349041 TI - Effects of hydrostatic pressure on the location of PRODAN in lipid bilayers and cellular membranes. AB - The effects of hydrostatic pressure on the location of 6-propionyl-2 (dimethylamino)naphthalene (PRODAN), an environmentally sensitive fluorescent probe, in phosphatidylcholine lipid bilayers and in goldfish brain synaptic membranes have been studied by fluorescence spectroscopy over the pressure range of 0.001-2 kbar. The emission spectrum of PRODAN in all the membrane systems examined exhibits two local maxima: one centers at around 435 nm and the other at about 510 nm. The intensity ratio of these two peaks, F435/F510, increases as pressure increases; in the particular case of dimyristoyl-L-alpha phosphatidylcholine multilamellar vesicles [DMPC(MLV)], a dramatic change in F435/F510 appears at the lipid phase transition pressure. As pressure varies, an isoemissive point is seen in both egg yolk phosphatidylcholines and goldfish brain synaptic membranes; however, no isoemissive point is observed in DMPC(MLV). The presence of an isoemissive point is attributed to a pressure-induced relocation of PRODAN from the "polar" disposition (the 510-nm peak) to the "less polar" disposition (the 435-nm peak). The absence of an isoemissive point in the case of DMPC(MLV) is probably due to the lack of void space in the lipid matrix, as a result of tight lipid packing. Apparently, the probe relocation takes place in unsaturated systems, and PRODAN favors a more hydrophobic environment under pressure. However, on the basis of the emission spectra, PRODAN seems to remain more or less at the interfacial region over the pressure range examined. In goldfish brain synaptic membranes, the PRODAN polarization increases with pressure, giving dT/dP values of 15-20 degrees C kbar-1 for both dispositions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349042 TI - Time-resolved europium(III) luminescence excitation spectroscopy: characterization of calcium-binding sites of calmodulin. AB - Pulsed-dye laser excitation and lifetime spectroscopy of the 7F0----5D0 transition of Eu3+ reveals details of the binding of this ion to the calcium binding sites of calmodulin (labeled I-IV, starting at the N-terminus). For 10 microM calmodulin Eu3+ binds quantitatively at sites I and II and more weakly at sites III and IV with Kd values of approximately 0.5 microM and 1.0 microM at the latter sites. In D2O solution the time course of luminescence emission of Eu3+ loaded calmodulin can be separated into three exponential components with lifetimes of 2.50 (sites I and II) and 1.70 and 0.63 ms (sites III and IV). This finding permits the time resolution of the excitation spectrum by determination of the amplitudes of the three components as the excitation wavelength is scanned across the spectral profile in 0.1-nm increments. The amplitudes (intensities at time t = O) are plotted as a function of wavelength and the results fitted to three Lorentzian peaks centered at 579.20, 579.40, and 579.32 nm in order of decreasing lifetimes. In H2O solution only two exponential luminescence decay components are resolvable with lifetimes of 0.41 and 0.27 ms, corresponding to sites I and II and sites III and IV, respectively. These results indicate that two water molecules are coordinated to the Eu3+ ions at sites I and II and at either site III or site IV, with three water molecules at the remaining site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349044 TI - Purification, composition, and structure of macrophage adhesion molecule. AB - Macrophage adhesion molecule (MAM) is a surface heterodimer consisting of the trypsin- and plasmin-sensitive glycopeptide gp160 (MAM-alpha) and the glycopeptide gp93 (MAM-beta). MAM, which is the guinea pig analogue of Mo1 and Mac-1, was purified from detergent lysates of peritoneal neutrophils by lentil lectin chromatography and M2-antibody chromatography. The pure heterodimer molecule was dissociated by acidic conditions (pH 3.5), and MAM-alpha and MAM beta were separated by M7-antibody chromatography. MAM-beta is an approximately 640 amino acid residue polypeptide with exceptionally high cysteine content. At 7.2 residues per 100 amino acids, Cys/2 of MAM-beta is more than 3 times the mean for 200 purified proteins. Reactivity with six beta-subunit-specific monoclonal antibodies recognizing at least four epitopes demonstrated that intrapeptide disulfide bonds are required to maintain the structure of MAM-beta. All six antibodies failed to react when MAM-beta was treated with reducing agents. MAM beta is 18% carbohydrate; the major monosaccharides are mannose, N acetylglucosamine, galactose, and sialic acid. MAM-beta is estimated to contain five to six N-linked carbohydrate units. MAM-alpha is an approximately 1100 residue polypeptide with lower Cys/2 content (2.0 residues per 100 amino acid residues). MAM-alpha is 21% carbohydrate. The major monosaccharides are mannose, N-acetylglucosamine, galactose, and sialic acid; the mannose content is higher in MAM-alpha than MAM-beta. MAM-alpha is estimated to contain 12 N-linked carbohydrate units. PMID- 3349043 TI - Fluorescence anisotropy decay demonstrates calcium-dependent shape changes in photo-cross-linked calmodulin. AB - We report dynamic fluorescence anisotropy measurements on the purified dityrosine derivative of calmodulin which was generated during UV irradiation of Ca2+ containing solutions of bovine brain calmodulin [Malencik, D. A., & Anderson, S. R. (1987) Biochemistry 26, 695]. Measurements were made by using a high repetition rate picosecond laser source combined with a microchannel plate photomultiplier. This permits the collection of very low noise anisotropy curves with essentially no convolution artifact. Measured anisotropies at high calcium concentrations are monoexponential, and at 20 degrees C, we recover a correlation time of 9.9 ns. When the temperature is varied from 4.8 to 31.8 degrees C, the recovered correlation time is proportional to the viscosity and inversely proportional to the absolute temperature, behavior expected for the rotational diffusion of a macromolecule whose conformation is independent of the temperature. The correlation time is compared to the theory describing the rotational diffusion of a dumbell. At high calcium concentrations, the cross linked calmodulin is elongated and has a length equal or nearly equal to that predicted by X-ray crystallographic results. In the absence of calcium, the molecule becomes highly compact and exhibits significant segmental motion. Intermediate calcium ion concentrations result in an intermediate degree of elongation and segmental motion. A small increase in the measured rotational correlation time of calmodulin upon the binding of melittin and mastoparan indicates that these peptides cause no major changes in the elongation of the molecule. When the cross-linked calmodulin is bound to troponin I, the complex rotates as a unit with a single rotational correlation time of 22 ns. PMID- 3349046 TI - Characterization of individual tryptophan side chains in proteins using Raman spectroscopy and hydrogen-deuterium exchange kinetics. AB - Two Raman bands at 880 and 1360 cm-1 of tryptophan (Trp) side chains have been found useful in structural studies of the side chains in proteins. The frequency of the 880-cm-1 band reflects the strength of H bonding at the N1H site of the indole ring: the lower the frequency is, the stronger the H bonding is. The intensity of the 1360-cm-1 band, on the other hand, is a marker of the hydrophobicity of the environment of the indole ring: particularly strong in hydrophobic environments. It is also demonstrated that a combination of stepwise deuteration of the tryptophan side chains and difference spectrum techniques is useful to observe these marker bands due to each side chain separately. The states of six tryptophans in lysozyme revealed by this Raman spectroscopic method in solution are compared with those by X-ray diffraction in crystal. The Raman data on the outer four Trp's are consistent with the X-ray structure, whereas significant differences between solution and crystal are suggested for the strength of H bonding of the most and second most buried Trp's. Characterization of four Trp's in alpha-lactalbumin shows that the two outer Trp's are moderately H bonded to solvent water and closely surrounded by aliphatic side chains while the inner two are not H bonded nor closely surrounded by aliphatic side chains. PMID- 3349045 TI - Lipid composition of PC12 pheochromocytoma cells: characterization of globoside as a major neutral glycolipid. AB - We have studied the lipid composition of PC12 pheochromocytoma cells cultured in the presence and absence of nerve growth factor (NGF). Neutral and acidic lipid fractions were isolated by column chromatography on DEAE-Sephadex and analyzed by high-performance thin-layer chromatography (HPTLC). The total lipid concentration was approximately 220 micrograms/mg of protein, and the concentration of neutral glycolipids was 1.6-1.8 microgram/mg of protein for both NGF-treated and untreated cells. The neutral glycolipid fraction contained a major component, which accounted for approximately 80% of the total and which was characterized as globoside on the basis of HPTLC mobility, carbohydrate analysis, fast atom bombardment mass spectrometry, and mild acid hydrolysis. The major fatty acids of globoside were C16:0 (10%), C18:0 (16%), C22:0 (23%), C24:1 (17%), and C24:0 (24%). C18 sphingenine accounted for almost all of the long-chain bases. The other neutral glycolipids were tentatively identified as glucosylceramide (15%), lactosylceramide (4%), and globotriosylceramide (4.5%). The concentration of ganglioside sialic acid was approximately 0.34 and 0.18 microgram/mg of protein for cells grown in the presence and absence of NGF, respectively. Although there was an increase in ganglioside concentration in NGF-treated cells, NGF did not produce any differential effects on the relative proportions of the individual gangliosides. Several of the gangliosides appear to contain fucose, and one of these was tentatively identified as fucosyl-GM1. Brain-type gangliosides of the ganglio series were also detected by an HPTLC-immunostaining method. However, the fatty acid and long chain base compositions of PC12 cell gangliosides (and their TLC mobility) differ from those of brain gangliosides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349047 TI - Hybrid hexanucleotide duplex containing cyclonucleotides and deoxynucleotides: the d(TA) segment can adopt a high anti left-handed double-helical structure. AB - It is known that oligonucleotides containing cyclonucleosides with a high anti (intermediate between anti and syn) glycosidic conformation adopt left-handed, single- and double-helical structures [Uesugi, S., Yano, J., Yano, E., & Ikehara, M. (1977) J. Am. Chem. Soc. 99, 2313-2323]. In order to see whether DNA can adopt the high anti left-handed double-helical structure or not, a self-complementary hexanucleotide containing 6,2'-O-cyclocytidine (C(o)), 8,2'-O-cycloguanosine (G(o)), thymidine, and deoxyadenosine, C(o)G(o)dTdAC(o)G(o), was synthesized. Imino proton NMR spectra and the results of nuclear Overhauser effect experiments strongly suggest that C(o)G(o)dTdAC(o)G(o) adopts a left-handed double-helical structure where the deoxynucleoside residues are involved in hydrogen bonding and take a high anti glycosidic conformation. A conformational model of the left handed duplex was obtained by calculation with energy minimization. Thus it appears that DNA can form a high anti, left-handed double helix under some constrained conditions, which is quite different from that of Z-DNA. PMID- 3349048 TI - NMR observability of ATP: preferential depletion of cytosolic ATP during ischemia in perfused rat liver. AB - The extent to which cellular metabolites are NMR observable is of fundamental importance in the interpretation of in vivo NMR studies. Analysis of ischemic rat liver shows that ATP resonances measured by 31P NMR decrease considerably faster than total tissue ATP measured in extracts. This discrepancy demonstrates that, in liver, ATP is not 100% observable. Furthermore, the data are consistent with the supposition that in situ mitochondrial ATP resonances are not normally observable by in vivo NMR techniques. The specificity of the NMR measurement for cytosolic ATP indicates that 31P NMR can be a valuable tool for the specific measurement of ATP in this compartment. PMID- 3349049 TI - Chemical probing of adenine residues within the secondary structure of rabbit 18S ribosomal RNA. AB - The location of unpaired adenine residues within the secondary structure of rabbit 18S ribosomal RNA was determined by chemical probing. Naked 18S rRNA was first prepared by digestion of purified 40S subunits with matrix-bound proteinase K in sodium dodecyl sulfate, thereby omitting the use of nucleic acid denaturants. Adenines within naked 18S rRNA were chemically probed by using either diethyl pyrocarbonate or dimethyl sulfate, which specifically react with unpaired nucleotides [Peattie, D. A., & Gilbert, W. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 4679-4682]. Adenine modification sites were identified by polyacrylamide sequencing gel electrophoresis either upon aniline-induced strand scission of 32P-end-labeled intact and fragmented rRNA or by primer extension using sequence-specific DNA oligomers with reverse transcriptase. The data indicate good agreement between the general pattern of adenine reactivity and the location of unpaired regions in 18S rRNA determined by comparative sequence analysis [Chan, Y.-L., Gutell, R., Noller, H. F., & Wool, I. G. (1984) J. Biol. Chem. 259, 224-230]. The overall reactivity of adenine residues toward single strand-specific chemical probes was, also, similar for both rabbit and Escherichia coli small rRNA. The number of strongly reactive adenines appearing within phylogenetically determined helical segments, however, was greater in rabbit 18S rRNA than for E. coli 16S rRNA. Some of these adenines were found clustered in specific helices. Such differences suggest a greater irregularity of many of the helical elements within mammalian 18S rRNA, as compared with prokaryotic 16S rRNA. These helical irregularities could be important for protein association and also may represent biologically relevant flexible regions of the molecule. PMID- 3349050 TI - Identification of the protein 4.1 binding site to phosphatidylserine vesicles. AB - Previous studies have shown that protein 4.1 is a multifunctional protein that binds to spectrin, actin, glycophorins, the anion channel protein, and phosphatidylserine (PS). In this report, we have characterized the binding of protein 4.1 and its major proteolytic fragments to phospholipid vesicles. Pure 125I-labeled protein 4.1 was incubated with PS liposomes, and the free protein 4.1 was separated by ultracentrifugation. Protein 4.1 bound to PS liposomes with a high affinity. At saturation, there was 9 X 10(-3) pmol of protein 4.1 bound/pmol of PS with a Kd of 3.3 X 10(-7) M. When the protein 4.1 containing liposomes were examined in an electron microscope, the protein 4.1 was found uniformly decorating the vesicles in a rosettelike fashion. Among peripheral membrane proteins tested (spectrin, actin, ankyrin, and protein 4.1), protein 4.1 showed the highest level of binding to PS. The binding of protein 4.1 to PS, one of the principal phospholipids of the inner half of the lipid bilayer, was considerably higher than the binding to phosphatidylcholine, that is principally located in the outer half of the lipid bilayer. To identify the structural domain of protein 4.1 involved in binding to the phospholipids, a mixture of proteolytic fragments of protein 4.1 was incubated with PS liposomes. The liposomes selectively retained the 30-kilodalton (kDa) basic domain of the protein, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/isoelectric focusing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349051 TI - Interaction of sperm histone variants and linker DNA during spermiogenesis in the sea urchin. AB - Several physical properties of sea urchin spermatid chromatin, which contains phosphorylated Sp H1 and Sp H2B histone variants, and mature sperm chromatin, in which these histones are dephosphorylated, were compared. Density, thermal stability, average nucleosomal repeat length, and resistance to micrococcal nuclease digestion are all increased in mature sperm relative to spermatid chromatin. Since the chromatins are identical in histone variant subtypes, the altered physical properties are not a consequence of changes in histone primary structure during spermiogenesis. The data are interpreted to mean that dephosphorylation of the N-terminal regions of Sp H1 and Sp H2B in late spermatid nuclei permits strong ionic binding of these highly basic regions to the extended linker, stabilizing the highly condensed structure of sperm chromatin. PMID- 3349052 TI - Nanosecond pulse fluorometry of conformational change in phenylalanine hydroxylase associated with activation. AB - Conformational change in rat liver phenylalanine hydroxylase associated with activation by phenylalanine or N-(1-anilinonaphth-4-yl)maleimide was investigated by measuring fluorescence spectra and fluorescence lifetimes of tryptophanyl residues as well as the probe fluorophore conjugated with SH groups of the hydroxylase. The fluorescence spectrum of tryptophan exhibited its maximum at 342 nm. It shifted by 8 nm toward longer wavelength accompanied by an increase in its intensity, by preincubation with 1 mM phenylalanine. The fluorescence intensity of tryptophan increased by 36% upon the activation. On the other hand, the binding of (6R)-L-erythro-tetrahydrobiopterin, a natural cofactor of the enzyme, induced a decrease in the fluorescence intensity by 79% without a shift of the maximum wavelength. The fluorescence lifetime of tryptophan of phenylalanine hydroxylase exhibited two components with lifetimes of 1.7 and 4.1 ns. The values of the lifetimes changed to 1.4 and 5.6 ns, respectively, upon the activation. It is considered that the change in the longer lifetime is correlated with the shift of the emission peak upon the activation. The values of both the lifetimes decreased to 0.64 and 3.6 ns upon the binding of (6R)-L-erythro tetrahydrobiopterin, which is coincident with the decrease in the fluorescence intensity. Conjugation of N-(1-anilinonaphth-4-yl)maleimide with SH of phenylalanine hydroxylase brought about a decrease in both the fluorescence intensity and the value of the shorter lifetime of the tryptophanyl residues, while the longer lifetime remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349053 TI - Dissection of the catalytic mechanism of isozyme 4-4 of glutathione S-transferase with alternative substrates. AB - The kinetic and chemical mechanism of isozyme 4-4 of rat liver glutathione (GSH) S-transferase was investigated by using several alternative peptide substrates including N-acetyl-GSH, gamma-L-glutamyl-L-cysteine (gamma-GluCys), N4-(malonyl-D cysteinyl)-L-2,4-diaminobutyrate (retro-GSH), and N4-(N-acetyl-D-cysteinyl)-L-2,4 diaminobutyrate (decarboxylated retro-GSH). The enzyme, which is normally stereospecific in the addition of GSH to the oxirane carbon of R absolute configuration in arene oxide substrates, loses its stereospecificity toward phenanthrene 9,10-oxide with the retro peptide analogues, giving a 2:1 mixture of the S,S and R,R stereoisomeric 9,10-dihydro-9-(S-peptidyl)-10 hydroxyphenanthrenes. The analogues with normal peptide bonds (N-acetyl-GSH and gamma-GluCys) show normal stereospecific addition. The kinetic mechanism of the enzyme was investigated by using the alternative substrate diagnostic with several 4-substituted 1-chloro-2-nitrobenzenes and GSH, N-acetyl-GSH, and gamma GluCys. Varying the concentration of electrophile vs the identity of the GSH analogue and the concentration of GSH vs the identity of the electrophile gave two sets of intersecting reciprocal plots, a result consistent with a random sequential kinetic mechanism. The pH profiles of kc and kc/Ksm [saturating GSH, variable 1-chloro-2,4-dinitrobenzene (1)] exhibit a dependence on a deprotonation in the enzyme-GSH-1 and enzyme-GSH complexes with molecular pKa's of 6.1 and 6.6, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349054 TI - Sodium-dependent chloride transport in basolateral membrane vesicles isolated from rabbit proximal tubule. AB - The mechanisms for Cl transport across basolateral membrane vesicles (BLMV) isolated from rabbit renal cortex were examined by using the Cl-sensitive fluorescent indicator 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ). The transporters studied included Cl/base exchange, Cl/base/Na cotransport, K/Cl cotransport, and Cl conductance. Initial rates of chloride influx (JCl) were determined from the measured time course of SPQ fluorescence in BLMV following inwardly directed gradients of Cl and gradients of other ions and/or pH. For a 50 mM inwardly directed Cl gradient in BLMV which were voltage and pH clamped (7.0) using K/valinomycin and nigericin, JCl was 0.80 +/- 0.14 nmol S-1 (mg of vesicle protein)-1 (mean +/- SD, n = 8 separate preparations). In the absence of Na and CO2/HCO3 in voltage-clamped BLMV, JCl increased 56% +/- 5% in response to a 1.9 pH unit inwardly directed H gradient; the increase was further enhanced by 40% +/ 3% in the presence of CO2/HCO3 and inhibited 30% +/- 8% by 100 microM dihydro 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Na gradients did not increase JCl in the absence of CO2/HCO3; however, an outwardly directed Na gradient in the presence of CO2/HCO3 increased JCl by 31% +/- 8% with a Na KD of 7 +/- 2 mM. These results indicate the presence of Cl/OH and Cl/HCO3 exchange, and Cl/HCO3 exchange trans-stimulated by Na. There was no significant effect of K gradients in the presence or absence of valinomycin, suggesting lack of significant K/Cl cotransport and Cl conductance under experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349055 TI - Poly(aspartic acid)-dependent fusion of liposomes bearing the quaternary ammonium detergent [[[(1,1,3,3-tetramethylbutyl)cresoxy]ethoxy]ethyl] dimethylbenzylammonium hydroxide. AB - Addition of the quaternary ammonium detergent [[[(1,1,3,3 tetramethylbutyl)cresoxy]ethoxy]ethyl] dimethylbenzylammonium hydroxide (DEBDA[OH]) and the fluorescent probes N-(7-nitro-2-1,3-benzoxadiazol-4 yl)phosphatidylethanolamine and N-(lissamine rhodamine B sulfonyl)phosphatidylethanolamine (N-NBD-PE and N-Rh-PE, respectively) to liposomes composed of phosphatidylcholine (PC) and cholesterol (chol) resulted in the formation of fluorescently labeled liposomes bearing DEBDA[OH]. Incubation of the anionic polymer poly(aspartic acid) (PASP) with such liposomes resulted in strong agglutination, indicating an association between the negatively charged PASP and the positively charged liposome-associated DEBDA[OH]. Addition of PASP to a mixture of fluorescently labeled and nonlabeled liposomes, both carrying DEBDA[OH], resulted in a significant increase in the extent of fluorescence, namely, fluorescence dequenching. The degree of the fluorescence dequenching was dependent upon the ratio between the nonfluorescent and the fluorescent liposomes, upon the temperature of incubation, and upon the amount of DEBDA[OH] which was associated with the liposomes. Electron microscopic observations revealed that large liposomes were formed upon incubation of liposomes bearing DEBDA[OH] with PASP. The results of the present work strongly indicate that the fluorescence dequenching observed is due to a process of PASP-induced liposome liposome fusion. PMID- 3349056 TI - Cytochrome P-450C-M/F, a new constitutive form of microsomal cytochrome P-450 in male and female rat liver with estrogen 2- and 16 alpha-hydroxylase activity. AB - A new cytochrome P-450 isozyme, P-450C-M/F, has been purified from untreated rat liver microsomes. The purified preparation was electrophoretically homogeneous and contained 12-15 nmol of P450/mg of protein and had a minimum molecular weight of 48,500. The NH2-terminal amino acid sequence of P-450C-M/F was different from that of other P-450's. Immunoblot analysis of microsomes demonstrated that P-450C M/F was present in the liver of untreated male as well as female rats. Treatment of rats with phenobarbital, 3-methylcholanthrene, or beta-naphthoflavone did not induce P-450C-M/F. Cytochrome P-450C-M/F exhibited little activities of 7 ethoxycoumarin and 7-ethoxyresorufin O-deethylation or hydroxylation of arylhydrocarbon, testosterone, androstenedione, and progesterone. In contrast, it was highly active in N-demethylation of ethylmorphine and benzphetamine and in 2- and 16 alpha-hydroxylation of estrogens, particularly that of estradiol. These studies establish that cytochrome P-450C-M/F is constitutively present in both male and female rats and suggest that it may be involved in the oxidative metabolism of estradiol, particularly in the formation of estriol, the uterotropic metabolite of estradiol. PMID- 3349057 TI - Nonrandom assembly of chromatin during hydroxyurea inhibition of DNA synthesis. AB - Incubation of MSB-1 chicken lymphoblastoid cells with hydroxyurea leads to a rapid 25-fold decrease in the incorporation of [3H]thymidine into DNA and a 5 fold decrease [3H]lysine into the nucleosome core histones. I have investigated whether the distortion in the normal proportion of histone-DNA synthesis results in alterations in the nucleosome assembly process and find that neither the stoichiometry of new histone synthesis nor the deposition is appreciably changed during hydroxyurea incubation. Protein cross-linking and micrococcal nuclease digestion show that the histones synthesized during hydroxyurea treatment form octamer structures and are assembled into typical nucleosome particles. Minor nucleosome subpopulations are found which exhibit altered sensitivity to nuclease digestion and which are depleted in new histones H3 and H4. When MSB-1 cells incubated in hydroxyurea are pulsed briefly with density-labeled amino acids and [3H]lysine, the radiolabeled core histone octamers formed are as dense as individual monomer histones. These results suggest that the newly synthesized histone octamers are uniformly dense and do not contain mixtures of new and old histones. Thus, histones synthesized during hydroxyurea incubation are deposited nonrandomly and do not exchange with preexisting histones. PMID- 3349058 TI - Sequence of a full-length cDNA for rat lung beta-galactoside-binding protein: primary and secondary structure of the lectin. AB - A full-length cDNA for rat lung beta-galactoside lectin (subunit Mr approximately 14,000, lectin 14K) was cloned and the nucleotide sequence determined. The deduced amino acid sequence agrees with the amino acid composition and direct amino acid sequence analysis of purified rat lung lectin peptides. We found that the amino-terminal alanine is blocked with an acetyl group. Comparison of the amino acid sequence with other proteins shows a high degree of homology only with other vertebrate lectin sequences, supporting the suggestion that these lectins may constitute a unique class of vertebrate proteins. The amino acid composition and sequence of lectin peptides, the sequence of lectin cDNA, and isoelectric focusing of purified lectin indicate that rat lung lectin 14K is composed predominantly of a single protein. In addition, rat uterus lectin 14K was found to be the same protein as that present in lung. We characterized the secondary and tertiary structure of rat lung lectin 14K by circular dichroism, by analytical ultracentrifugation, and by computer analysis of its primary structure. Results of these experiments suggest that lectin 14K is primarily a hydrophilic protein with an asymmetric, elongated structure consisting of approximately equal amounts of alpha helix, beta sheet, beta turn, and random coil. We found that Cys-2 and Cys-130 react most rapidly with iodoacetamide; one or both of these residues may be primarily responsible for the thiol requirement of lectin activity. PMID- 3349059 TI - Structural characterization of recombinant hepatitis B surface antigen protein by mass spectrometry. AB - The primary structure of recombinant hepatitis B surface antigen protein produced in yeast has been confirmed by mass spectrometric peptide mapping. These studies corroborate more than 85% of the amino acid sequence derived by sequencing of the gene and identified the presence of an acetyl moiety on approximately 70% of the NH2-terminal methionine residues. Prior to the present work, direct structural analysis was largely prevented by the insolubility of this integral membrane protein and its primary degradation fragments in aqueous buffers and by partial blockage of the NH2 terminus. These difficulties were overcome by preparative isolation using electroelution of the monomeric 226 amino acid protein from a polyacrylamide electrophoretic gel in the presence of sodium dodecyl sulfate. Chymotryptic digestion of the reduced and carboxymethylated monomer produced a large number of small, predominantly hydrophobic peptides ideally suited for peptide mapping by fast atom bombardment mass spectrometry. The percentage of NH2 terminal methionine blocked by acetyl was determined by a new strategy involving cyanogen bromide cleavage, permethylation, and gas chromatography/mass spectrometry identification and quantitation of the N-methyl-N-acetylhomoserine produced. PMID- 3349060 TI - Interactions of oleic acid with liver fatty acid binding protein: a carbon-13 NMR study. AB - 13C NMR spectroscopy was used to probe the structural interactions between carboxyl-13C-enriched oleic acid (18:1) and rat liver fatty acid binding protein (FABP) and the partitioning of 18:1 between FABP and unilamellar phosphatidylcholine (PC) vesicles. Spectra of systems containing 2-8 mol of 18:1/mol of FABP (but no PC) exhibited one carboxyl resonance (182.2 ppm) corresponding to FABP-bound 18:1. At pH values less than 8.0, an additional carboxyl resonance, corresponding to unbound 18:1 in a lamellar phase, was observed. Both resonances exhibited ionization shifts with estimated apparent pKa values of less than 5 (bound 18:1) and greater than 7 (unbound 18:1). The intensity of the resonance corresponding to FABP-bound 18:1 increased with increasing 18:1/FABP mole ratio and at 8/1 mole ratio indicated that at least 2 and 6 mol of 18:1/mol of FABP were FABP-bound at pH 7.4 and 8.6, respectively. NMR spectra of systems containing equal concentrations (w/v) of FABP and PC and from 1 to 4 mol of total fatty acid (FA)/mol of FABP exhibited two 18:1 carboxyl resonances (182.2 and 178.5 ppm, pH 7.4). The downfield resonance corresponded to FABP-bound 18:1 and the upfield resonance to PC vesicle bound 18:1. At 1/1 mole ratio (FA/FABP), the intensities of both resonances were approximately equal, but at 4/1 mole ratio the resonance for PC vesicle bound 18:1 was 3-fold more intense than that for FABP-bound 18:1. The following conclusions are reached: (i) The carboxyl groups of 18:1 bound to liver FABP experience only one type of binding environment (the aqueous milieu adjacent to the protein surface).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349061 TI - Analysis of an enzyme-substrate complex by X-ray crystallography and transferred nuclear Overhauser enhancement measurements: porcine pancreatic elastase and a hexapeptide. AB - The hexapeptide substrate Thr-Pro-nVal-NMeLeu-Tyr-Thr reacts with porcine pancreatic elastase sufficiently slowly that accelerated crystallographic data collection procedures and two-dimensional transferred nuclear Overhauser enhancement measurements could be used to study the geometry of binding. Both studies report a time-averaged population of the Michaelis complex state, prior to proteolysis. This result provides an important data point along the reaction coordinate pathway for serine proteases. Crystallographic data to 1.80-A resolution were used in the structure analysis with refinement to an R-factor of 0.19. PMID- 3349062 TI - Crotoxin, a phospholipase A2 neurotoxin from the South American rattlesnake Crotalus durissus terrificus: purification of several isoforms and comparison of their molecular structure and of their biological activities. AB - Crotoxin, the major toxin of the venom of the South American rattlesnake Crotalus durissus terrificus is a mixture of several isoforms that differ slightly in their molecular structure. The toxin consists of two nonidentical subunits: a basic and weakly toxic phospholipase A2, component B, and an acidic and nontoxic subunit, component A. In the present investigation, we have used fast-performance liquid chromatography (FPLC) on anionic and cationic exchange columns to purify isoforms of both crotoxin subunits. Two component A isoforms and four component B isoforms were obtained in a homogeneous state, and their purity was verified by isoelectric focusing in polyacrylamide gels. The amino acid composition of the purified component A and component B isoforms was in good agreement with the protein sequences determined previously with mixtures of isoforms. The amino acid compositions indicated that for both crotoxin components the isoforms differed only by the replacement of few amino acid residues. Eight crotoxin complexes have been prepared in a homogeneous state by reassociation of pure component A and component B isoforms. The quantitative comparison of enzymatic and pharmacological properties of the reconstituted crotoxins indicated that the two component A isoforms had identical properties, whereas the four component B isoforms fell in two classes: crotoxin complexes formed with component B isoforms of the first class were enzymatically less active and pharmacologically more potent than those obtained with component B isoforms of the second class. PMID- 3349063 TI - Nucleotide binding to uncoupling protein. Mechanism of control by protonation. AB - Nucleotide binding to the isolated uncoupling protein (UCP) from brown adipose tissue of hamster was studied in detail under equilibrium conditions. Besides microequilibrium dialysis and elution chromatography, a rapid anion-exchange procedure was adapted. From the concentration dependence, the KD and the binding capacity to UCP of ATP, ADP, and GTP and of the ATP analogues 5'-adenylyl imidodiphosphate (AMPPNP) and adenosine 5'-O-(3-thiotriphosphate) were determined. Elucidation of the pH dependence of nucleotide binding was the prime topic. From pH 4.6 to 7.5, the KD varies by almost 2 orders of magnitude, reaching the limits of the equilibrium methods. The pKD of GTP and ATP decreases from 6.3 to 4.3 with increasing pH. For ADP, the pKD varies only from 6.0 to 4.8. The intricate course of the pH dependence shows a "break point" of the pKD around pH 6.3, where the slope (pKD/pH) changes between about -0.2 and -1. Another break point above pH 7.2 produces a pKD/pH = -2 for ATP and GTP only. AMPPNP binding has a lower affinity (pKD about 5.8-4.1) and a pH dependence slope of -1 with no break. The breaks suggest involvement of the last ionization group (pKH approximately equal to 6.7) of the nucleotide phosphate. This agrees with the absence of a break for AMPPNP and with the shift by Mg2+ of the break for ATP to lower pH. The best-fitting model for the pH dependence requires in addition a H+ dissociating group at the binding site of UCP with a pKH approximately equal to 4, dominating the whole pH range. A second group effective above pH 7.0 amplifies the debinding specifically of ATP, not CTP or ADP. Further, the model implies binding of both NTP4- and the protonated NTPH3- or NDP3- and NDPH2- forms, however, with different affinities. On this basis, the relation between the measured overall KD and the intrinsic KD's of both nucleotide forms and the various H+ dissociation constants is derived, and the corresponding pKD/pH curves are calculated. A good fit with the data is obtained with a pKH = 3.8 for the UCP center and a pKH = 6.8 for nucleotides and with affinity ratios of 50 for NTP4 /NTPH3- and 100 for NDP3-/NDPH2-. The binding of the protonated nucleotide NTPH3- is seen only at a low pH, but with the analogue AMPPNPH3- with pKH = 7.6 it dominates the whole pH range to pH 7.2 with corresponding low affinity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3349064 TI - Determination of local conformational stability in fragment 96-133 of bovine growth hormone by high-resolution H NMR spectroscopy. AB - The specific assignment of resonances in the 400-MHz nuclear magnetic resonance (NMR) spectrum of fragment 96-133 (AII) of bovine growth hormone (bSt) is described. Assignments have been made with homonuclear two-dimensional techniques, in particular that of sequential resonance assignment. Complete assignments were possible for the spin systems of 16 residues out of a total of 38 and partial assignments for another 5. Assignment of resonances to either residue type or a class of residue was possible for a number of other spin systems. Analysis of the type of nuclear Overhauser effect (NOE) indicates that segments 96-110 and 130-133 are nonregular stable structures and that the segment 111-127, which putatively spans the alpha-helix, is not sufficiently stable to generate NOEs. PMID- 3349065 TI - Accessibilities of the sulfhydryl groups of native and photooxidized lens crystallins: a fluorescence lifetime and quenching study. AB - Fluorescence lifetime and acrylamide quenching studies on the N-(iodoacetyl)-N' (5-sulfo-1-naphthyl)ethylenediamine (1,5-IAEDANS)-labeled sulfhydryl groups of bovine lens alpha-, beta H-, and gamma-crystallins were carried out to characterize the microenvironment of the sulfhydryls and changes produced by singlet oxygen mediated photooxidation. For the untreated proteins, the lifetimes of the major decay component of the fluorescence-labeled crystallins were 15.2, 14.4, and 13.0 ns, and the quenching rate constant, kq, values were 16.6 x 10(7), 26.9 x 10(7), and 32.7 x 10(7) M-1 s-1 for alpha-, beta H-, and gamma crystallins, respectively. The results indicate that as the polarity of the sulfhydryl site increased (i.e., its lifetime decreased), its accessibility to collisional quenching by acrylamide also increased. The minor decay component of the fluorescence label was not significantly quenched by acrylamide for all three classes of crystallins. When the proteins were irradiated in the presence of methylene blue, in a system generating singlet oxygen, the kq value for acrylamide quenching of the major decay component of alpha-crystallin decreased to zero, while its lifetime decreased to 6 ns. Neither the lifetime nor the kq of alpha-crystallin recovered completely in the presence of the singlet oxygen quencher sodium azide. Light-induced binding of the photosensitizer methylene blue to the crystallins was observed by absorption spectroscopy. The bound photosensitizer partially quenches the fluorescence lifetime of the N-acetyl-N' (5-sulfo-1-naphthyl)ethylenediamine (AEDANS) label in irradiated alpha crystallin. Further decrease in the lifetime occurs as a result of the singlet oxygen mediated conformational change. The results suggest that the fluorescence lifetime of the AEDANS is fully quenched in the irradiated alpha-crystallin and there is no further quenching by acrylamide. An increase in the fraction of the minor component of beta H-crystallin which was inaccessible to acrylamide quenching was observed after irradiation. There was no effect of irradiation on the kq for acrylamide quenching of the major component of the decay of AEDANS bound to beta H- or gamma-crystallins. Static quenching was found to contribute significantly to the steady-state quenching plots of the polar sulfhydryl sites of irradiated alpha-crystallin and of untreated and irradiated beta H- and gamma crystallins, but it had no detectable role in the case of untreated alpha crystallin. Fluorescence anisotropy of the AEDANS label bound to the crystallins was higher in the irradiated crystallins as compared with the controls. PMID- 3349066 TI - Effect of differences in optical properties of intermediate oxygenated species of hemoglobin A0 on Adair constant determination. AB - Careful evaluation of the so-called isosbestic properties of oxygenated and deoxygenated hemoglobin spectra demonstrates that the spectral changes are not strictly linear with respect to the degree of saturation. In order to quantify the extent of nonlinearity, optical measurements of O2 binding to human hemoglobin were made at different wavelengths in the Soret region approaching the presumed isosbestic point. The results indicate that the extinction coefficient of intermediate oxygenated hemoglobin is 1% less than that of the fully oxygenated hemoglobin, with a resulting 3% (+/- 0.15%) nonlinearity effect on measurements taken at the peak of the oxygenated hemoglobin spectrum (414 nm). The lack of isosbestic conditions allows one to investigate the functional properties of the oxygenated intermediates directly. The small difference in the absorbance of different oxygenated species has practically no influence on the determination of Adair constants at wavelengths removed from the critical isosbestic region. PMID- 3349067 TI - Description of the molecular mechanism of cooperativity in human hemoglobin cannot be limited to a first-order free energy coupling concept. AB - Studies of the linkage between ligand binding and subunit assembly of oligomeric proteins have extensively used the concept of free energy coupling. The "order" of these free energy couplings was introduced [Weber, G. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 7098-7102] as the number of subunits that must be liganded to alter specific intersubunit interactions. This concept dictates that the ligation of fewer subunits has no effect, but once the order number of subunits becomes ligated, the specific intersubunit interaction energy between those particular subunits is completely eliminated. Weber's report claims that the free energy coupling between oxygen binding and the dimer-tetramer subunit assembly in stripped human hemoglobin A is "first order". This conclusion is based on the analysis of a set of previously published equilibrium constants [Mills, F. C., Johnson, M. L., & Ackers, G. K. (1976) Biochemistry 15, 5350-5362]. I subsequently reported that the original experimental data, from which the equilibrium constants were derived, are consistent with both the first-order and "second-order" free energy coupling concepts [Johnson, M. L. (1986) Biochemistry 25, 791-797]. I also demonstrated that more precise recent experimental data [Chu, A. H., Turner, B. W., & Ackers, G. K. (1984) Biochemistry, 23, 604-617] are consistent with both the first-order and second-order free energy coupling concepts. A recent article [Weber, G. (1987) Biochemistry 26, 331-332] disagrees that the oxygen-binding data for human hemoglobin A are consistent with a second order model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349068 TI - Electron conduction between b cytochromes of the mitochondrial respiratory chain in the presence of antimycin plus myxothiazol. AB - The b haems of the bc1 complex of bovine heart mitochondria were poised with succinate and fumarate so that only the high-potential haem (b-562) was reduced, and then isolated from further redox exchange with the ubiquinone pool by adding antimycin and myxothiazol. A transmembrane electric potential difference was then developed, either by electron flow from [Ru(NH3)6]Cl2 to oxygen or by ATP hydrolysis. The small difference spectrum, caused by the electric field, indicated 32-55% oxidation of b-562 with concomitant reduction of b-566. No lag greater than 0.1 s was detectable between the initiation of respiration and the development of the difference spectrum, thus providing a direct demonstration of (fairly) rapid electron transfer between the b haems. PMID- 3349069 TI - Transport of pyruvate by luminal membrane vesicles from pars convoluta and pars recta of rabbit proximal tubule. AB - The characteristics of renal transport of pyruvate by luminal membrane vesicles from pars convoluta and pars recta of rabbit proximal tubule were studied. It was found that the uptake of pyruvate in these vesicle preparations occurred by means of multiple transport systems. An electrogenic and Na+-requiring system confined to pars convoluta, exists for transport of pyruvate with an intermediate affinity, KA = 0.71 +/- 0.08 mM. In vesicles from pars recta, the uptake of pyruvate was mediated by a dual transport system with a high (KA1 = 0.30 +/- 0.05 mM) and low affinity (KA2 = 5.75 +/- 0.82 mM). The relation of these three pyruvate transport systems to the transport of other monocarboxylates and dicarboxylates was determined by examination of the inhibitory effect of L lactate, beta-hydroxybutyrate and L-malate on the renal uptake of pyruvate. It was found that L-malate efficiently reduced the uptake of pyruvate by vesicles from pars convoluta, while addition of monocarboxylates (L-lactate, beta hydroxybutyrate) has no effect on the transport of pyruvate in this region of proximal tubule. Furthermore, it was observed that Na+-dependent uptake of L malate was specifically inhibited to about the same extent by 1 mM pyruvate. These findings strongly suggest that pyruvate and L-malate are taken up by the same transport system in vesicles from pars convoluta, which is different from that of L-lactate and beta-hydroxybutyrate. Experiments designed to investigate the substrate specificity for the high and low affinity system for pyruvate in pars recta, revealed that monocarboxylates (L-lactate, beta-hydroxybutyrate) substantially inhibit pyruvate transport at the low, but not the high substrate concentration, indicating that all monocarboxylates compete for the same high affinity transport system. By contrast, L-malate at low concentrations preferentially inhibited the low-affinity system for pyruvate. This observation led us to suggest that L-malate and pyruvate share a common transport system in pars recta with low affinity for pyruvate and high affinity for L-malate. PMID- 3349070 TI - Calcium diphosphatidate membrane traversal is inhibited by common phospholipids and cholesterol but not by plasmalogen. AB - Phosphatidate-mediated Ca2+ membrane traversal is inhibited by phospholipids (PL) such a phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), sphingomyelin and lysoPC, but not by PC-plasmalogen. Kinetics of Ca2+ traversal through a 'passive' bilayer consisting of OH-blocked cholesterol show competition between PC and phosphatidic acid (PA); it appears likely that a Ca(PA.PC) complex is formed which is not a transmembrane ionophore but will reduce the amount of phosphatidic acid available for the formation of the ionophore, Ca(PA)2. PS and PI may inhibit Ca2+-traversal in the same manner by forming Ca(PA.PL) complexes. We suggest that PC-plasmalogen, with one of the Ca2+ chelating ester CO groups missing, cannot engage in calcium cages, i.e., Ca(PA.PL) complexes, and thus does not interfere with Ca(PA)2 formation. Double reciprocal plotting of Ca2+ traversal rates in cholesterol-containing liposomes vs. calcium concentration suggests that cholesterol inhibits Ca2+ traversal by competing with Ca2+ for PA. The inhibition does not seem to be caused by a restructuring or dehydration of the membrane 'hydrogen belts' affected by cholesterol; most probably, it is due to hydrogen bonding of the cholesterol-OH group to a CO group of PA; this reduces the amount of PA available for the calcium ferry. The inhibition by sphingomyelin and lysoPC may also be explained by their OH group interacting with PA via hydrogen bonding. The pH dependence of Ca2+ traversal suggests that H[Ca(PA)2]- can serve as Ca2+ cross-membrane ferry but that at physiological pH, [Ca(PA)2]2- is the predominant ionophore. In conclusion, the results indicate that Ca2+ traversal is strongly dependent on the structure of the hydrogen belts, i.e., the membrane strata occupied by hydrogen bond acceptors (CO of phospholipids) and donors (OH of cholesterol, sphingosine), and that lipid hydrogen belt structures may regulate storage and passage of Ca2+. PMID- 3349071 TI - Influence of structural modifications on the phase behavior of semi-synthetic cerebroside sulfate. AB - Cerebroside sulfate (galactosylceramide I3-sulfate) containing alpha-hydroxy lignoceric acid (C24:0h-CBS), nervonic acid (C24:1-CBS), or hexacosanoic acid (C26:0-CBS) was prepared by a semi-synthetic procedure and studied by differential scanning calorimetry. The phase behavior of these species in 2 M KCl was compared to that of shorter chain length hydroxy and non-hydroxy fatty acid species reported earlier. All three of the new lipids undergo metastable phase behavior similar but not identical to the other species. In addition, the metastable phase behavior of all of the non-hydroxy fatty acid species was found to be more complex than previously thought, with several phases of high transition temperatures and enthalpies possible. Fatty acid hydroxylation inhibits the transition from the metastable to some of the more stable phases. It also significantly increases the phase transition temperatures of both the metastable and stable phases indicating that it contributes to the hydrogen bonding network formed between the lipid molecules and helps overcome the lateral repulsive effect of the negatively charged sulfate. The C-15 cis double bond significantly lowers the temperature and enthalpy of the phase transition indicating that it increases the lateral separation of the lipid molecules and decreases the intermolecular hydrogen bonding interactions. However, it does not prevent formation of a more stable phase. By comparing the effect of various structural modifications reported here and earlier it could be concluded that fatty acid chain length has little effect on the phase transition temperature and enthalpy. This suggests that the forces between the lipid molecules may be dominated by head group interactions rather than interactions between the lipid chains. However, fatty acid chain length has a significant effect on the tendency of the hydroxy fatty acid species to form the more stable phase. The ease of formation of the stable phase increases with increase in chain length. Thus an increase in chain length helps overcome the kinetic barrier to stable phase formation presented by hydroxylation of the fatty acid. PMID- 3349072 TI - The 'delta pH'-probe 9-aminoacridine: response time, binding behaviour and dimerization at the membrane. AB - The fluorescence quenching of 9-aminoacridine (9-AA) after imposition of a transmembrane pH gradient (inside acidic) in liposomes has been investigated for a number of different lipid systems. The initial fluorescence decrease after a rapid pH jump, induced in the extravesicular medium by a stopped-flow mixing technique, was ascribed to a response of 9-AA to the imposed pH gradient and not to changes in the vesicular system itself. Time constants for this fluorescence quenching are in the range of several hundred milliseconds at 25 degrees C. Fluorescence recovery which should be correlated to the dissipation of the pH gradient occurs in the 100 s time range and is 10-30-times faster than the delta pH decay monitored with the entrapped hydrophilic pH-indicator dye pyranine. The quenching was severely hindered below the lipid phase transition of dipalmitoylphosphatidylglycerol. No delta pH-induced quenching was obtained in lipid vesicles containing only zwitterionic, net uncharged phosphatidylcholine headgroups. For the occurrence of quenching, the presence of negatively charged headgroups, i.e. phosphatidylglycerol or phosphatidylserine, was necessary. The extent of quenching, at a specific pH difference applied, had a cooperative dependency (Hill coefficient approximately 2) on the number of negative headgroups in the membrane and on the concentration of unquenched (unbound) 9-AA molecules. The concentration of quenched 9-AA molecules was furthermore proportional to the number of dimer-excimer complexes of 9-AA which are formed during the quenching process. PMID- 3349074 TI - Effect of fluorophore linkage position of n-(9-anthroyloxy) fatty acids on probe distribution between coexisting gel and fluid phospholipid phases. AB - The quenching of probe fluorescence by spin-labeled phospholipid has been used to determine the distribution of a series of n-(9-anthroyloxy) fatty acids between coexisting gel and fluid liquid-crystal phases in multilamellar phospholipid vesicles. The phase distribution ratio in every case is found to favor the fluid lipid phase, but is much greater between fluid and Ca2+-induced gel than between fluid and thermal gel. For a given gel type, n-(9-anthroyloxy)stearic acids with n = 3, 6, 9 or 12 as well as 11-(9-anthroyloxy)undecanoic acid all exhibit similar behavior, favoring the fluid phase by about a factor of 4 over thermally induced lipid gel phase and by 18 over Ca2+-induced gel phase. 16-(9 Anthroyloxy)palmitic acid, with the bulky probe at the terminus of the 16-carbon chain, favors the fluid phase less strongly, by a factor of 1.5 or 11 over thermally-induced or Ca2+-induced gel phase, respectively, indicating better packing of this probe in phospholipid gel phases. PMID- 3349073 TI - Location and ion-binding of membrane-associated valinomycin, a proton nuclear magnetic resonance study. AB - Valinomycin, incorporated in small unilamellar vesicles of perdeuterated dimyristoylphosphatidylcholine, reveals several well-resolved 1H-NMR resonances. These resonances were used to examine the location, orientation and ion-binding of membrane-bound valinomycin. The order of affinity of membrane-bound valinomycin for cations is Rb+ greater than K+ greater than Cs+ greater than Ba2+, and binding is sensitive to surface change. The exchange between bound and free forms is fast on the NMR time scale. The intrinsic binding constants, extrapolated to zero anion concentration, are similar to those determined in aqueous solution. Rb+ and K+ show 1:1 binding to valinomycin, whereas the stoichiometry of Cs+ and Ba2+ is not certain. Paramagnetic chemical shift reagents and nitroxide spin label relaxation probes were used to study the location and orientation of valinomycin in the membrane. Despite relatively fast exchange of bound cations, the time average location of the cation-free form of valinomycin is deep within the bilayer under the conditions of these experiments. Upon complexation to K+, valinomycin moves closer to the interfacial region. PMID- 3349075 TI - Photoaffinity labelling of a 150 kDa (Na + K + Cl)-cotransport protein from duck red cells with an analog of bumetanide. AB - We have used a radiolabelled, benzophenone analog of bumetanide, 4-[3H]benzoyl-5 sulfamoyl-3-(3-thenyloxy)benzoic acid ([3H]BSTBA) to photolabel plasma membranes from duck red blood cells. BSTBA, like bumetanide, is a loop diuretic and a potent inhibitor of (Na + K + Cl) cotransport, and [3H]BSTBA binds to intact duck red cells with a high affinity similar to that of [3H]bumetanide (K 1/2 congruent to 0.1 microM). We incubated duck red cells with [3H]BSTBA, then lysed the cells and exposed the ghosts to ultraviolet light. The ghosting and photolysis was done at 0 degree C to prevent dissociation of the [3H]BSTBA. The ghosts were then sonicated to remove the nuclei and run on SDS-polyacrylamide gels. Analysis of H2O2-digested gel slices revealed [3H]BSTBA to be incorporated into a protein of approx. 150 kDa. This is the same molecular weight we obtain for a protein from dog kidney membranes which is photolabelled by [3H]BSTBA in a manner highly consistent with labelling of the (Na + K + Cl) cotransporter (Haas and Forbush (1987) Am. J. Physiol. 253, C243-C252). Several lines of evidence strongly suggest that the 150 kDa protein from duck red cell membranes is an integral component of the (Na + K + Cl)-cotransport system in these cells: (1) Photolabelling of this protein by [3H]BSTBA is blocked when 10 microM unlabelled bumetanide is included in the initial incubation medium with [3H]BSTBA; (2) Photoincorporation of [3H]BSTBA into the 150 kDa protein is markedly increased when the initial incubation medium is hypertonic or contains norepinephrine, conditions which similarly stimulate both (Na + K + Cl) cotransport and saturable [3H]bumetanide binding in duck red cells; (3) The photolabelling of this protein shows a saturable dependence on [3H]BSTBA concentration, with a K1/2 (0.06 microM) similar to that for the reversible, saturable binding of [3H]BSTBA and [3H]bumetanide to duck red cells; and (4) [3H]BSTBA photoincorporation into the 150 kDa protein, like saturable [3H]bumetanide binding to intact cells, requires the simultaneous presence of Na+, K+, and Cl- in the medium containing the radiolabelled diuretic. PMID- 3349076 TI - Membrane fluidity and lipid composition of rat small intestinal brush-border membranes during postnatal maturation. AB - Fluidity and lipid composition of rat small intestinal brush-border membranes (BBM) were studied during maturation in five age groups: newborns, sucklings (1-3 weeks), weaned (4-6 weeks), juveniles (8-10 weeks), and adults (12 weeks). Brush border membrane fluidity was measured by steady-state fluorescence polarization. Fluorescent probes used were: 1,6-diphenyl-1,3,5-hexatriene, 1-(4 trimethylammonium)phenyl)-6-phenyl-1,3,5-hexatriene, and a set of n-(9 anthroyloxy) fatty acids. Fluorescence anisotropy measured with all fluorophores was increased in adult versus newborn rats (P less than 0.004). The weight ratio of saturated to cis-unsaturated fatty acids increased from birth to the suckling age (P less than 0.0004). The cholesterol to phospholipid molar ratio increased from birth to the weaned age (P less than 0.0001). Cholesterol to protein ratio and phospholipid to protein ratio decreased after the weaned age (P less than 0.004). The results not only describe maturational changes of brush-border membranes but also give a better understanding of the correlations between biophysical and biochemical data in biological membranes. PMID- 3349077 TI - Evidence that trans-bilayer interdigitation of glycosphingolipid long chain fatty acids may be a general phenomenon. AB - 'Interdigitation' is a term coined to describe the phenomenon whereby pure phosphatidylcholines with intramolecular fatty acid chain length heterogeneity when hydrated to form bilayers may insert the methyl ends of long fatty acids from one side across more than half of the membrane thickness to protrude amongst the acyl chains of the opposite side of the bilayer (Keough, K.M.W. and Davis, P.J. (1979) Biochemistry 18, 1453-1459; Huang, C. and Mason, J.T. (1986) Biochim. Biophys. Acta 864, 423-470). In this article we address the fate of long fatty acid chains of glycosphingolipids present as minor components in membranes of non interdigitating phosphatidylcholines. In this pursuit, derivatives of galactosyl ceramide, lactosyl ceramide, globoside and GM1 were synthesized having either 18 carbon or 24-carbon fatty acid with a spin label covalently attached at C-16. Labelled glycolipids were incorporated at 1-2 mol% into bilayers of synthetic phosphatidylcholines, their mixtures with cholesterol, or natural egg phosphatidylcholine. In each case the C-16 carbon of the glycolipid long chain fatty acid showed considerably greater 'order' and immobility than did C-16 of the fatty acid which was similar in length to the host matrix phospholipids. We interpret this as strong evidence that the long chain fatty acid interdigitates across the mid point of the bilayer in the systems studied. Clearly this phenomenon did not require that the phospholipid host matrix have mixed chain lengths. Furthermore it was totally independent of glycolipid family: for a given host matrix and (glycolipid) fatty acid chain length the order parameter values found were the same amongst all four glycolipid families tested. PMID- 3349078 TI - Characterization of the transport system for beta-lactam antibiotics and dipeptides in rat renal brush-border membrane vesicles by photoaffinity labeling. AB - The uptake of the alpha-aminocephalosporin cephalexin into brush-border membrane vesicles from rat renal cortex was independent on an inward H+-gradient in contrast to the intestinal transport system. The transport system could be irreversibly inhibited by photoaffinity labeling. Two binding polypeptides for beta-lactam antibiotics and dipeptides with apparent molecular weights 130,000 and 95,000 were identified by photoaffinity labeling with [3H]benzylpenicillin and N-(4-azido[3,5-3H]benzoyl) derivatives of cephalexin and glycyl-L-proline. The uptake of cephalexin and the labeling of the respective binding proteins was inhibited by beta-lactam antibiotics and dipeptides as with intestinal brush border membranes. These data indicate that the transport systems for beta-lactam antibiotics and dipeptides in the brush-border membrane from rat kidney and small intestine are similar but not identical. PMID- 3349079 TI - The Na+-Ca2+ exchange system in vascular smooth muscle cell membrane vesicles isolated from cultured cells and from tissue is similar. AB - The existence of a Na+-Ca2+ exchange system was investigated in sarcolemmal vesicles isolated from cultured cells of dog mesenteric artery. When Na+-loaded membrane vesicles were suspended in a Na+-free KCl medium to create an outwardly directed Na+ concentration gradient across the membrane, a time-dependent uptake of Ca2+ was observed. This uptake of Ca2+ was drastically reduced when the vesicles were suspended in NaCl medium to eliminate the Na+ concentration gradient across the membrane. Monensin also decreased Ca2+ uptake in Na+-loaded vesicles. The apparent Km for Ca2+ was 2.97 microM and the apparent maximum velocity was 4.27 nmol/min per mg protein. The data indicate that a Na+-Ca2+ exchange system exists in sarcolemmal membranes isolated from cultured cells and that it is similar to the system in membranes isolated from the tissue. PMID- 3349080 TI - On the use of regular solution theory as a theoretical frame for the analysis of membrane phenomena. AB - The structural heterogeneity of the phospholipid membrane causes difficulties in the analysis of membrane functions. These difficulties can be overcome by using probes which dissolve preferentially into one of the regions, provided that a general theory correlating probe behaviour to membrane structure exists. The use of regular solution theory (RST) as a theoretical frame for membrane analysis is examined below, and it is concluded that some, but not all, of the relations furnished by the theory are useful for membrane analysis. Using these relations, it is concluded that the hydrophobic region of the membrane has a stabilizing effect. The polar region is less stable and changes faster than the hydrophobic region. Diffusion rates are smaller in the hydrophobic region. PMID- 3349081 TI - Measurement of rapid membrane permeation in cell suspensions by application of a generalized capillary method. AB - An improved version of the capillary technique for the determination of diffusion coefficients has been developed as a simple method of measuring membrane permeabilities of single cells suspended at relative densities between 0.70 and 0.97. A new, generalized theoretical formulation to describe the diffusion process of a solute in a composite system was derived using a series-parallel pathway model with explicit consideration of the diffusion pathways inside and between the cells. This renders the technique insensitive to unstirred layer effects. Any single cell population of known size distribution may be investigated. High permeabilities (above 5.10(-3) cm/s) can be measured with the greatest precision, but lower permeabilities, down to a limit of about 5.10(-4) cm/s, may also be determined by the method. Measurements in erythrocyte suspensions have been made using non-electrolytes such as hexanol, water and ethylene glycol as test solutes. The permeabilities obtained agree with the values obtained by much more sophisticated equipment. Cell shape was shown to be without significant influence on the permeability data obtained. The procedure may become of particular interest for measurement of suspensions of membrane vesicles. PMID- 3349083 TI - Influenza virus-model membrane interaction. A morphological approach using modern cryotechniques. AB - The membrane fusion activity of influenza virus was characterized morphologically using a model system composed of a highly purified influenza B virus suspension and ganglioside-containing zwitterionic liposomes. Electron microscopical analysis was performed after a combination of fast-freezing with either freeze fracture or freeze-substitution-thin sectioning, ensuring maximal time resolution and avoiding preparation artifacts. In a parallel fluorescence 'lipid mixing' fusion assay, influenza virus-membrane fusion was characterized biochemically. Biochemical and morphological data are in full agreement, indicating negligible membrane fusion activity at neutral pH and high fusion activity at low pH. The freeze-fracture morphology strongly suggests a local point contact between viral and liposomal membrane at neutral pH, and a local point fusion mechanism for influenza virus-membrane fusion upon lowering of the pH. Fusion is followed by lipid mixing, lateral diffusion of viral spike proteins and exposure of viral contents at the inner liposomal surface. PMID- 3349082 TI - The interaction of n-alkanols with lipid bilayer membranes: a 2H-NMR study. AB - The interaction of eight n-alkanols with bilayers of dimyristoylphosphatidylcholine (DMPC) has been studied by deuterium nuclear magnetic resonance (2H-NMR). At comparable temperatures and concentrations of solute in the bilayer, order parameters measured at the 1-methylene segment of the n-alkanols show a maximum for n-dodecanol. For both n-dodecanol and n tetradecanol, orientational ordering shows a maximum at the C-4 to C-7 methylene segments, with labels at both ends of the n-alkanol exhibiting reduced order. These observations are consistent with earlier findings for n-octanol and n decanol. Unlike the longer chain n-alkanols, ordering in n-butanol decreases from the hydroxyl group end to the methyl group end of the molecule. Orientational ordering at nine inequivalent sites in DMPC, has also been measured as a function of temperature, for bilayers containing n-butanol, n-octanol, n-dodecanol and n tetradecanol. At the 3R,S sites on the glycerol backbone, for comparable temperatures and solute concentrations, n-butanol produces a larger disordering than the other n-alkanols. This result probably reflects the greater fraction of time spent by the hydroxyl group of n-butanol in the vicinity of the lipid polar head group compared with the hydroxyl group in longer chain n-alkanols. It was found that n-octanol orders the acyl chains of DMPC, unlike n-butanol which disorders them, and the longer chain n-alkanols which have little effect. Within experimental error, the effect of n-dodecanol on order at all sites in DMPC is the same as n-tetradecanol. The influence of n-alkanols on DMPC ordering at twelve sites has been compared with that of cholesterol which is shown to interact with DMPC bilayers in a distinctly different manner from the n-alkanols. PMID- 3349084 TI - Effects of ganglioside GM1 on DNA synthesis in isolated nuclei and on the activity of DNA polymerase alpha derived from S-phase HeLa cells. AB - Ganglioside GM1 inhibited either DNA synthesis in isolated nuclei or the activity of DNA polymerase alpha fractionated from S-phase HeLa cells. The concentrations of GM1 necessary for 50% inhibition were about 5 microM and 10 microM for nuclei and DNA polymerase alpha, respectively. The GM1 inhibition of the enzyme activity was suppressed by the addition of 0.05% Triton X-100. Neither gangliotetraosylceramide (asialo-GM1) nor free N-acetylneuraminic acid inhibited the enzyme activity. These facts suggest that GM1, probably in the form of micelles, could influence the enzyme activity by behaving as a polyanionic macromolecule. The kinetic studies indicate that the GM1 inhibition of the enzyme activity was not competitive with the substrate, deoxythymidine triphosphate, but rather with the template DNA. Binding of GM1 and DNA polymerase alpha was suggested by the cocentrifugation of GM1 and the enzyme fraction after their preincubation. It was also observed that other acidic glycolipids, i.e., brain sulphatide and seminolipid, also inhibited the enzyme activity, whilst neutral galactosylceramide did not. The inhibitory influences of these sulphate esters of glycolipids were, similarly to GM1, suppressed by the addition of 0.05% Triton X 100. PMID- 3349085 TI - Supercoiling response of E. coli promoters with different spacer lengths. AB - The effect of negative supercoiling on a series of synthetic Escherichia coli promoters has been investigated. These promoters carry perfect consensus sequences at the -35 and -10 regions, but with different spacer lengths (Aoyama, T. et al. (1983) Nucleic Acids Res. 11, 5855-5864). Topoisomeric plasmids carrying these synthetic promoters were constructed, and their activities were compared by detecting in vitro transcripts with the probe-hybridization method. In the relaxed state, the one with 17 basepairs (bp) spacing showed the highest activity, and the activity steeply decreased both sides of the optimal spacing. Similar results have been observed by run-off transcription. By introducing negative superhelicity, the 17 bp spacing promoter showed a relatively little response to supercoiling. In contrast, the activities of those with 16 and 18 bp spacings were markedly stimulated by supercoiling, with the mean, negative superhelical density (-sigma) which gave the maximum activity being about the same for the 16-18 bp spacing promoters (-sigma = 0.03 to 0.04). The promoter with 19 bp spacing, which showed no activity in the relaxed state, exhibited a significant activity at higher superhelicities (-sigma = 0.06). Even the 20 bp spacing promoter showed some activity by increasing superhelicity, while the 15 bp spacing promoter did not. On the basis of these observations, possible mechanisms by which negative supercoiling of DNA stimulates the protomer activity are discussed. PMID- 3349086 TI - Kinetic study of alpha-chymotrypsin-catalyzed synthesis of kyotorphin. AB - A kinetic analysis of reaction-rate data obtained during a series of optimization experiments of the alpha-chymotrypsin-catalyzed synthesis of kyotorphin has been performed. The kinetic data have been fitted to a model equation derived from a proposed sequential mechanism, which has been further simplified to a first-order equation as a function of the substrate consumption. Statistical tests performed validate the model, since the fitted constants were statistically significant. In addition, the activation energy of the process has been calculated and resulted to be 32.5 +/- 2.3 kJ/mol which is within the range of other enzymatic reactions. PMID- 3349087 TI - Enzymatic synthesis of p-nitrophenyl N,N',N'',N'',N''''-pentaacetyl-beta chitopentaoside in water-methanol system; significance as a substrate for lysozyme assay. AB - Transchitooligosylation from (GlcNAc)5 to the 4-position of PNP-GlcNAc was efficiently induced through lysozyme catalysis in an aqueous solution containing methanol with a high concentration. Use of the aqueous methanol system in this reaction not only guaranteed solubility of PNP-GlcNAc substrate, but also resulted in a remarkable increase in PNP-(GlcNAc)5 production. PNP-(GlcNAc)5 was substrate for lysozyme assay compared with PNP-(GlcNAc)4. PMID- 3349088 TI - Allowance for effects of electrostatic repulsion on protein dimerization. AB - A simple procedure for assessing the extent of electrostatic effects on protein dimerization is described and illustrated by application to published results on the ionic strength dependence of the dimerization constant for alpha-chymotrypsin at pH 4 (Aune, K.C., Goldsmith, L.C. and Timasheff, S.N. (1971) Biochemistry 10, 1617-1622). From the analysis it is concluded that the inverse dependence of alpha-chymotrypsin dimerization upon ionic strength is predominantly a general electrostatic effect, rather than a consequence of repulsion between two specific charged residues on the adjacent monomers comprising dimer. PMID- 3349090 TI - Carnitine and acetylcarnitine in red blood cells. AB - Carnitine and acetylcarnitine were found to be present in human erythrocytes. Their presence was not as a factor of leucocyte contamination. Carnitine is present within the erythrocyte at a level comparable to that of the plasma, whilst acetylcarnitine is more concentrated within the cell. Red blood cell carnitine and acetylcarnitine do not freely exchange with plasma but intra erythrocyte acetylcarnitine has a significant relationship to the plasma levels. PMID- 3349089 TI - CD studies on the reversed heme orientation in monomeric Glycera dibranchiata hemoglobins. AB - Circular dichroism spectra of three monomeric components of Glycera dibranchiata hemoglobins are reported. Contrary to what is found for most hemoglobins and myoglobins, G. dibranchiata hemoglobins display largely negative dichroic spectra in the Soret region. Independent NMR measurements have shown that the same monomeric hemoglobin components contain the heme moiety predominantly (greater than 85%) oriented in a reversed way with respect to the orientation which occurs in most hemoglobins and myoglobins. On the basis of these independent NMR studies, and also of previous data on other invertebrate hemoproteins, a correlation appears evident between reversed heme orientation in hemoglobins and negative ellipticity in the Soret CD spectrum. This represents a simple tool to evaluate this aspect of heme asymmetric environment. PMID- 3349091 TI - Lipoprotein lipase in liver. Release by heparin and immunocytochemical localization. AB - We have previously demonstrated that infusion of Intralipid to rats causes a pronounced increase of the lipoprotein lipase activity in the liver. In this paper we study where in the liver this lipoprotein lipase is located. When isolated livers from Intralipid-treated rats were perfused with heparin, substantial amounts of lipoprotein lipase were released into the perfusate. The identity of the lipase activity was demonstrated by specific inhibition with antisera to lipoprotein lipase, and to hepatic lipase, respectively, and by separation of the two lipase activities by chromatography on heparin-Sepharose. We have also studied the localization of both enzymes by an immunostaining procedure based on post-embedding incubation of ultrathin tissue sections with specific antibodies which were then visualized using protein A-colloidal gold complexes. There was no marked difference in localization for the two enzymes which were both seen at the luminal side of endothelial cells, at the interdigitations of the space of Disse and inside both hepatocytes and endothelial cells. Thus, lipoprotein lipase is present in the liver in positions similar to where the functional pool of hepatic lipase is located and analogous to where lipoprotein lipase is found in extrahepatic tissues. These results raise the possibility that the enzyme has a functional role in the liver. PMID- 3349092 TI - Preferential metabolism by macrophages of conditioned rabbit hypercholesterolemic remnant lipoproteins. AB - Rabbits were fed a diet containing 1% cholesterol, and lipoproteins were isolated from their plasma by sequential ultracentrifugation. Lipoprotein remnants (d = 1.019-1.063) were conditioned by incubation with bovine aortic smooth muscle cells for 24 h and then incubated for 4 h with J774 cells or mouse peritoneal macrophages. Conditioning of remnants and low-density lipoproteins resulted in enhancement of their uptake and metabolism by the macrophages in culture. The macrophages metabolized conditioned remnant lipoproteins more extensively than controls at all concentrations tested. Addition of 10% safflower oil or 10% butter to the 1% cholesterol diet resulted in a molar ratio of linoleic/oleic acid of 1.62 and 0.62 in plasma neutral lipids and of 5.7 and 2.5 in plasma phospholipids. Conditioned remnants, derived after safflower oil feeding, were metabolized more extensively by macrophages than those obtained after butter feeding. This was also true for control remnants (preincubated without cells). Thiobarbituric acid-reactive substances were higher in remnants from safflower oil-fed than butter-fed rabbit plasma prior to and after conditioning. Mouse peritoneal macrophages metabolized remnant lipoproteins more extensively than low density lipoproteins. The present results indicate that modification of remnant lipoproteins, the major atherogenic fraction of cholesterol-fed rabbit plasma, results in their enhanced metabolism by macrophages, and that an increase in the linoleic/oleic acid ratio in these lipoproteins might enhance their susceptibility to peroxidative modification. PMID- 3349093 TI - Purification and characterisation of a non-specific lipid transfer protein from goat liver. AB - A non-specific lipid transfer protein has been purified from the pH 5.1 supernatant of goat liver by DEAE-cellulose, CM-cellulose and Sephadex G-75 column chromatography. The protein shows a single band on polyacrylamide gel electrophoresis and transfers 450 nmol of phosphatidylcholine per min per mg of protein under the present assay condition. This protein has a subunit molecular weight of 12,000 and an isoelectric point of 8.65. Amino acid analysis reveals the absence of methionine. Histidine has been identified as the only N-terminal amino acid. Besides phosphatidylcholine, the protein transfers phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine and cholesterol. Chemical modification studies showed the involvement of free amino and thiol groups in the maintenance of the transfer activity of the goat liver protein. PMID- 3349094 TI - The Zellweger syndrome: deficient chain-shortening of erucic acid (22:1 (n-9)) and adrenic acid (22:4 (n-6)) in cultured skin fibroblasts. AB - In the Zellweger syndrome where peroxisomes are absent, extremely long fatty acids (24:0 and 26:0) accumulate in tissues suggesting that these fatty acids are normally beta-oxidized in the peroxisomes. Previous studies with rat hepatocytes suggest that peroxisomes are also important in oxidation of C22 unsaturated fatty acids. This study shows that cultured fibroblasts from normal human controls shorten [14-14C]erucic acid (22:1(n-9)) to oleic acid (18:1(n-9)) efficiently while Zellweger fibroblasts are deficient in chain-shortening. [2-14C]Adrenic acid (22:4(n-6)) is oxidized in control fibroblasts probably by chain-shortening to arachidonic acid (20:4(n-6)). Only a little adrenic acid is oxidized in Zellweger fibroblasts. Linolenic acid (18:3(n-3)) is desaturated and chain elongated in both control and Zellweger fibroblasts. The results support the view that peroxisomes play a normal physiological role in the shortening of C22 unsaturated fatty acids and that this function is deficient in Zellweger fibroblasts. PMID- 3349095 TI - Hormonal effects on fatty-acid synthase in cultured fetal rat lung; induction by dexamethasone and inhibition of activity by triiodothyronine. AB - We previously reported that administration of dexamethasone to the pregnant dam increased the activity of fatty-acid synthase (EC 2.3.1.85) in fetal rat lung and that this effect was reduced when triiodothyronine (T3) was also administered. To determine whether the hormones act directly on the lung, we examined their effects in organ culture. Explants of 18-day and 19-day fetal rat lung were cultured with 100 nM dexamethasone or 100 nM T3, the two hormones together or no hormone at all for 48 h, after which fatty-acid synthase was assayed. Dexamethasone increased fatty-acid synthase activity at both gestational ages. T3 alone had no effect on 18-day, but decreased the activity in 19-day explants by 20%. T3 reduced the stimulatory effect of dexamethasone from 177% to 102% and from 61% to 22% in 18- and 19-day explants, respectively. The effects of dexamethasone and T3 were concentration dependent, with EC50 (concentration achieving 50% of the maximum effect) values of 0.65 nM and approx. 25 nM, respectively. This dexamethasone EC50 is lower than the reported Kd for dexamethasone binding, but the T3 EC50 is considerably higher than its reported Kd. The physiological significance of the T3 effect is, therefore, not clear. The effect of dexamethasone was not apparent until at least 12 h after exposure to the hormone and it was abolished by actinomycin D. Immunoprecipitation with antibody against rat liver fatty-acid synthase showed that there was more fatty acid synthase in the dexamethasone-treated than in the control cultures. The potency order of glucocorticoids in stimulating fatty-acid synthase was similar to that previously reported for specific nuclear glucocorticoid binding. These data show that dexamethasone and T3 act directly on the fetal lung and that the stimulatory effect of the glucocorticoid on fatty-acid synthase is due to new protein synthesis. PMID- 3349096 TI - Concerted action of human carboxyl ester lipase and pancreatic lipase during lipid digestion in vitro: importance of the physicochemical state of the substrate. AB - The pancreatic enzyme carboxyl ester lipase (CEL) has been shown to hydrolyse a large number of different esters, including triacylglycerols, cholesteryl esters and retinyl esters with an absolute requirement for bile salts. Some of the lipids that are substrates for CEL can also be hydrolysed by pancreatic lipase. In order to investigate the relative roles of human CEL and pancreatic lipase, the two enzymes were incubated on a pH-stat with isotope-labelled lipid substrate mixtures in physicochemical forms resembling the state of the dietary lipids in human intestinal contents. In the first set of experiments, cholesteryl oleate (CO) and retinyl palmitate (RP) were solubilised in an emulsion of triolein (TO) stabilised by egg phosphatidylcholine and bile salts. Lipase (always added together with its cofactor, colipase) hydrolysed TO, with monoolein and oleic acid as end-products, whereas CEL alone could not hydrolyse TO in the presence of phosphatidylcholine (PC). Lipase alone did not hydrolyse CO or RP, but CEL did hydrolyse these esters if lipase was present. Release of [3H]glycerol from labelled TO increased only slightly if CEL was added compared to lipase alone, suggesting that monoolein hydrolysis was slow under these conditions. In the second set of experiments, CO and RP were dissolved in bile salt/monoolein/oleic acid dispersions with varying bile salt concentrations. CEL hydrolysed CO and RP more rapidly in a system with a high bile salt concentration containing mixed micelles than in a system with a low bile salt concentration, where the lipids were dispersed in the form of mixed micellar and non-micellar aggregates; both types of aggregate have been reported to exist in human intestinal contents. In conclusion, these data suggest that the main function of CEL under physiological conditions is to hydrolyse cholesteryl and retinyl esters, provided that the triacylglycerol oil phase is hydrolysed by pancreatic lipase, which probably causes a transfer of the substrate lipids of CEL from the oil emulsion phase to an aqueous bile salt/lipolytic product phase. Depending on the bile salt/lipolytic product ratio, the substrate will reside in either micellar or non micellar lipid aggregates, of which the micellar state is preferred by CEL. PMID- 3349097 TI - Effect of harvesting methods, growth conditions and growth phase on diacylglycerol levels in cultured human adherent cells. AB - The cellular mass of sn-1,2-diacylglycerols, which are intracellular second messengers which activate protein kinase C, were quantitatively determined with an enzymatic assay. The method employed to harvest cultured human skin fibroblasts or human epidermal A431 cells prior to extraction of lipid into chloroform/methanol affected diacylglycerol (DAG) levels. Scraping or trypsinization significantly increased DAG levels. A method was devised to allow reliable and reproducible DAG measurements from adherent cells. The addition of methanol prior to scraping was shown to stop cellular metabolism and to permit accurate quantitation. Importantly, this solvent was compatible with cultures grown on plastic. Using this method, growth conditions which could affect DAG levels were investigated. Changes in the osmolality of the culture medium did not affect the DAG levels of A431 cells; exposure of A431 cells to acidic pH or elevated temperature lowered DAG levels. In contrast to fibroblasts, the total DAG levels of A431 cells continued to increase during serum deprivation. The highest DAG levels, normalized to phospholipids, were observed during the exponential growth phase. This ratio dropped when the cultures reached confluency. These experiments also demonstrated that A431 cells possess higher DAG levels than do normal fibroblasts. The function of DAG in cellular regulation is discussed. PMID- 3349098 TI - Pharmacological actions of 17 beta-oestradiol on articular cartilage chondrocytes and chondrosarcoma chondrocytes in the absence of oestrogen receptors. AB - (1) Pharmacological concentrations (greater than 10(-5) M) of 17 beta-oestradiol inhibited 35S-labelled proteoglycan synthesis in bovine articular cartilage explant cultures. They also inhibited 35S-labelled proteoglycan synthesis and 3H labelled protein synthesis in cell cultures of chondrocytes from bovine articular cartilage and Swarm rat chondrosarcoma. Maximal inhibition was about 30-50%. Physiological concentrations (10(-9)-10(-8) M) of oestradiol had no effect on the synthesis of either protein or proteoglycan. (2) The inhibitory action of high concentrations of oestradiol on these biosynthetic pathways is not common to all steroids since 10(-4) M cortisol had no effect on articular chondrocyte cell cultures. 10(-4) M testosterone had a similar action to oestradiol. (3) Neither physiological nor pharmacological concentrations of 17 beta-oestradiol had any effect on 35S-labelled proteoglycan turnover in the cartilage explant system. (4) 10(-5) M oestradiol inhibited cell division in cultures of articular chondrocytes which had entered the log growth phase. 10(-7) M oestradiol had no effect on articular chondrocyte growth. (5) In male rats implanted with silastic capsules releasing 17 beta-oestradiol, increase in body weight was retarded by about 25% over a period of 6 weeks, compared to control rats. Rat chondrosarcoma grew to the same size in oestrogen-treated rats as it did in controls. (6) Oestrogen receptors could not be detected in freshly isolated bovine articular chondrocytes or in rat chondrosarcoma. (7) In conclusion, neither the mitotic rate of articular chondrocytes nor their proteoglycan metabolism is under the direct physiological control of oestradiol. Growth and biosynthetic activity of the rat chondrosarcoma chondrocytes are independent of either direct control by the hormone or control effected by oestradiol regulation of a second hormone or growth factor. PMID- 3349099 TI - Glucocerebrosidase, a lysosomal enzyme that does not undergo oligosaccharide phosphorylation. AB - Labelling of cultured human skin fibroblasts from either control subjects or patients with mucolipidosis II (I-cell disease) with [32P]phosphate resulted in tight association of phosphate with immunoprecipitated glucocerebrosidase, a membrane-associated lysosomal enzyme. Endoglycosidase F digestion of the immunoprecipitated glucocerebrosidase did not release labelled phosphate, suggesting that the phosphate was not associated with the oligosaccharide moiety of this glycoprotein. Purification of the enzyme from cells labelled with [32P]phosphate and [35S]methionine by an immunoaffinity chromatography procedure, which included a washing step with detergent, resulted in complete separation of the phosphate label from the peak of glucocerebrosidase activity and methionine labelling. We conclude that oligosaccharide phosphorylation, which is essential for transport of soluble lysosomal enzymes to the lysosomes in fibroblasts, does not occur in glucocerebrosidase. PMID- 3349100 TI - Non-enzymatic glycation of antithrombin III in vitro. AB - Non-enzymatic glycation of antithrombin III (AT-III) has been proposed as a significant contributor to the increased incidence of thrombo-occlusive events in diabetics. AT-III, isolated from normal human plasma by means of heparin affinity and ion-exchange chromatography, was incubated with 0-0.5 M glucose in neutral phosphate buffer at 37 degrees C. The extent of non-enzymatic glycation could be monitored by uptake of radioactivity as well as by binding to a phenylboronate affinity resin, which effectively retards AT-III containing ketoamine-linked glucose. Non-enzymatically glycated AT-III (approx. 1 mol glucose/mol protein) bound heparin nearly as efficiently as non-glycated AT-III. The two AT-III preparations were equally active in inhibiting thrombin cleavage of chromogenic substrate. Following incubation with [14C]glucose, structural analyses of cyanogen-bromide-cleaved peptides of enzymatically glycated AT-III showed that the [14C]glucose adducts were distributed over many sites on the molecule. This lack of specificity contrasts with the restricted sites of modification on hemoglobin, albumin and ribonuclease A, and explains why non-enzymatic glycation of AT-III has little if any effect on its function. PMID- 3349101 TI - A comparison of two anesthetic techniques for the study of rat skeletal muscle high-energy phosphates in vivo using 31P-NMR. AB - 31P-Nuclear magnetic resonance (NMR) spectroscopy was used to evaluate in vivo rat quadriceps ATP, phosphocreatine (PCr), inorganic phosphate (Pi) and tissue pH during anesthesia with ketamine/xylazine (K/X) or isoflurane (IS). A surface coil was used to receive signals from the quadriceps muscle of rats positioned in a wide-bore horizontal magnet. The PCr/beta-ATP ratios determined from the NMR spectra were 4.34 +/- 0.19 (K/X) and 4.40 +/- 0.28 (IS). Tissue pH was 7.09 +/- 0.05 (K/X) and 7.13 +/- 0.07 (IS). Metabolic stability of quadriceps PCr and ATP was demonstrated during both K/X and IS anesthesia, but the K/X-anesthetized animals had longer sleep time, lower food consumption, and lower body weight post anesthesia than the IS-anesthetized animals. The PCr/beta-ATP ratio in quadriceps of repetitively IS-anesthetized rats did not fluctuate diurnally. In addition, the animals recovered rapidly and continued to gain weight following the multiple brief IS anesthetic procedures. These data indicate that serial in vivo investigations of high-energy-phosphate metabolism in small animals can be accomplished using 31P-NMR spectroscopy and IS anesthesia, which has several advantages over K/X anesthesia for these types of studies. PMID- 3349102 TI - Retention of oxidized glutathione by isolated rat liver mitochondria during hydroperoxide treatment. AB - The addition of tert-butyl hydroperoxide (t-BuOOH) to isolated mitochondria resulted in oxidation of approximately 80% of the mitochondrial reduced glutathione (GSH) independently of the dose of t-BuOOH (1-5 mM). Concomitant with the oxidation of GSH inside the mitochondria was the formation of GSH-protein mixed disulfides (protein-SSG), with approximately 1% of the mitochondrial protein thiols involved. A dose-dependent rate of GSH recovery was observed, via the reduction of oxidized GSH (GSSG) and a slower reduction of protein-SSG. Although t-BuOOH administration affected the respiratory control ratio, the mitochondria remained coupled and loss of the matrix enzyme, citrate synthase, was not increased over the control and was less than 3% over 60 min. A slow loss of GSH out of the coupled non-treated mitochondria was not increased by t-BuOOH treatment, in fact, a dose-dependent drop of GSH levels occurred in the medium. However, no GSSG was found outside the mitochondria, indicating the necessary involvement of enzymes in the t-BuOOH-induced conversion of GSH to GSSG. The absence of GSSG in the medium also suggests that, unlike the plasma membrane, the mitochondrial membranes do not have the ability to export GSSG as a response to oxidative stress. Our results demonstrate the inability of mitochondria to export GSSG during oxidative stress and may explain the protective role of mitochondrial GSH in cytotoxicity. PMID- 3349103 TI - Purification of bovine liver S-adenosylhomocysteine hydrolase by affinity chromatography on blue dextran-agarose. AB - S-Adenosylhomocysteine (AdoHcy) hydrolase (adenosylhomocysteinase, EC 3.3.1.1) was purified from bovine liver by conventional protein purification procedures (differential centrifugation, ammonium sulfate fractionation and DEAE-cellulose chromatography) followed by affinity chromatography on blue dextran coupled to agarose. The enzyme was eluted from the blue dextran-agarose column with adenosine and the adenosine was removed by chromatography on Sephadex G-75. The affinity chromatography step resulted in a substantial increase in total AdoHcy hydrolase activity (about 600%) suggesting either removal of some inhibitory substance or a change in the structure of the protein producing a more catalytically efficient enzyme. The isolation procedure afforded over 3400-fold purification of the enzyme, which was shown to be homogeneous by polyacrylamide gel electrophoresis. Using high pressure liquid chromatography, the nucleotide content of the freshly purified enzyme was determined to be 2 mol of nicotinamide adenine nucleotide per mol of enzyme tetramer. The ratio of the reduced to the oxidized form of the nucleotide was correlated to the activity of the enzyme preparation. PMID- 3349104 TI - Isolation and structural characterization of sialic acid-containing storage material from mucolipidosis I (sialidosis) fibroblasts. AB - Sialic acid-containing storage material was isolated from cultured human mucolipidosis I (sialidosis) fibroblasts by gel permeation chromatography on Bio Gel P-6 followed by medium-pressure anion-exchange chromatography on Mono Q. The structure determination of the isolated sialyloligosaccharides was carried out by 500-MHz 1H-NMR spectroscopy in conjunction with sugar analysis and analytical HPLC. The storage material showed completely sialylated mono-, di- and triantennary N-glycosidic N-acetyllactosamine oligosaccharides having the Man beta 1----4GlcNAc sequence at the reducing end in common. Heterogeneity occurred with respect to the linkages between terminal sialic acid and the penultimate galactose residues (alpha 2----3/alpha 2----6). It turned out that all the identified carbohydrate chains are consistent with the neuraminidase deficiency. PMID- 3349105 TI - Inhibition of GTP cyclohydrolase I by pterins. AB - Pterins inhibit rat liver GTP cyclohydrolase I activity noncompetitively. Reduced pterins, such as 7,8-dihydro-D-neopterin, (6R,S)-5,6,7,8-tetrahydro-D-neopterin, 7,8-dihydro-L-biopterin, (6R)-5,6,7,8-tetrahydro-L-biopterin, L-sepiapterin, and DL-6-methyl-5,6,7,8-tetrahydropterin are approximately 12-times more potent as inhibitors than are oxidized pterins, such as D-neopterin, L-biopterin, and isoxanthopterin. They are also 12-times more potent than folates, such as folic acid, dihydrofolic acid, (+/-)-L-tetrahydrofolic acid, and aminopterin. The Ki values for 7,8-dihydro-D-neopterin, 7,8-dihydro-L-biopterin, and (6R)-5,6,7,8 tetrahydro-L-biopterin are 12.7 microM, 14.4 microM, and 15.7 microM, respectively. These results suggest that mammalian GTP cyclohydrolase I may be regulated by its metabolic end products. PMID- 3349106 TI - Species differences in sensitivity of nucleoside transport in erythrocytes and cultured cells to inhibition by nitrobenzylthioinosine, dipyridamole, dilazep and lidoflazine. AB - Differences in sensitivity of uridine transport in erythrocytes and cultured cells to inhibition by dipyridamole, dilazep and lidoflazine were largely species specific; uridine transport in human cells, and probably in pig and rabbit cells, was 2-3- and 10-times more sensitive to inhibition by dipyridamole (IC50 approx. 50 nM) and about 10- and 20-times more sensitive to dilazep inhibition (IC50 approx. 5 nM) than transport in mouse and rat cells, respectively. Uridine transport in human erythrocytes and HeLa cells was strongly inhibited by lidoflazine (IC50 10-140 nM), whereas that in both mouse and rat cells was highly resistant (IC50 greater than 10 microM). Superimposed on species-specific differences were some cell type specific differences in sensitivity of nucleoside transport to these inhibitors. Uridine transport in Walker 256 rat carcinoma cells was more resistant to dipyridamole and dilazep than that of other rat cells. Transport in human Hep-2 cells was more resistant to lidoflazine (IC50 2000 nM) than that of human erythrocytes and HeLa cells, whereas it showed similar sensitivity to dilazep and dipyridamole. Uridine transport in Chinese hamster cells was also more resistant to dilazep than that of baby hamster kidney cells. In addition HeLa cells and clones thereof expressed uridine transporters (about 50% each) with difference of about 1000-fold in sensitivity to inhibition by dilazep (IC50 approx. 5 nM and 5 microM, respectively). PMID- 3349108 TI - Stimulation of IgG production by glucocorticoids in human myeloma lymphoblasts. AB - LICR-LON-HMy2 cells (HMy2 cells), an established line of human myeloma lymphoblasts, produce and secrete IgG, and have been used for production of human human hybridomas. We have previously shown that HMy2 cells are growth-inhibited by glucocorticoids and contain high affinity, saturable, steroid-specific glucocorticoid receptors. Here we report that treatment for 0-4 days with the synthetic glucocorticoid dexamethasone (1,4-pregnadien-9-fluoro-16 alpha-methyl 11 beta,17 alpha,21-triol-3,20-dione) leads to time-dependent increases in IgG secretion rates as measured by goat anti-human IgG antibodies in an enzyme-linked immunosorbent assay. Stimulation of IgG secretion is dependent on the concentration of dexamethasone employed, with half-maximal stimulation occurring between 1.10(-9) and 1.10(-8) M, and maximal stimulation occurring at 1.10(-7) M. Stimulation of IgG secretion is specific for active glucocorticoids such as cortisol and dexamethasone; treatment of cells with 17 beta-estradiol, progesterone, dihydrotestosterone, and aldosterone has little, if any, effect on IgG secretion. Finally, dexamethasone markedly stimulates both secreted and newly synthesized IgG, as determined by continuous and pulse labeling of extracellular and intracellular proteins, respectively, followed by binding to protein A Sepharose, gel electrophoresis, and autoradiography. Thus, although dexamethasone effects on post-translational or secretory processes have not been ruled out, our data indicate that increased biosynthesis of IgG accounts for most, if not all, of the observed increase in IgG secretion rates. In summary our results demonstrate that despite the known immunosuppressive effects of glucocorticoids, these hormones can stimulate IgG biosynthesis and secretion in human myeloma lymphoblasts in vitro. PMID- 3349107 TI - Effect of thyroid state on cytosolic free calcium in resting and electrically stimulated cardiac myocytes. AB - The effects of the thyroid state on the cytosolic free Ca2+ concentration, [Ca2+]i, of resting and K+-depolarized cardiomyocytes were studied using the fluorescent Ca2+ indicator fura2. The mean resting [Ca2+]i in euthyroid myocytes (89 +/- 8 nM) was not significantly different from that in hyperthyroid myocytes (100 +/- 14 nM). The resting O2-consumption rate was identical for both groups when expressed per mg protein, but a 35% higher value was observed in the hyperthyroid group when expressed per cell on account of the cellular hypertrophy induced by thyroid hormone. Potassium induced depolarization (50 mM [K+]0) raised the level of [Ca2+]i by 50% in both groups. When ATP-coupled respiration was blocked with oligomycin, the 50 mM K+-induced rise in [Ca2+]i was accompanied in both groups by a 40% rise in glycolytic activity as inferred from measurement of lactate production. Ca2+-fluorescence transients were recorded from electrically stimulated myocytes of euthyroid, hyperthyroid and hypothyroid rats. The time taken to reach peak fluorescence (TPL) and that to 50% decay of peak fluorescence (RL0.5) decreased in the direction hypothyroid----hyperthyroid, indicating an increase in Ca2+ fluxes in the same direction. Isoproterenol (1 microM) enhanced the peak Ca2+ fluorescence in electrically stimulated hypothyroid and euthyroid myocytes but not in hyperthyroid myocytes. Both the TPL and RL0.5 were decreased by isoproterenol in euthyroid, but more so in hypothyroid myocytes. None of these parameters were influenced by isoproterenol in the hyperthyroid group. We conclude that (1) thyroid hormone increases neither the O2-consumption rate nor the level of [Ca2+]i of resting cardiomyocytes and (2) the effects of the beta receptor-agonist isoproterenol on Ca2+ transients of electrically stimulated myocytes, are inversely related to the documented changes in beta-receptor density in heart tissue occurring with alterations in the thyroid state. PMID- 3349109 TI - ADP-ribosylation suppresses phosphorylation of the L-type pyruvate kinase. AB - L-type pyruvate kinase (EC 2.7.1.40) purified from pig liver was ADP-ribosylated by incubation with NAD and ADP-ribosyltransferase purified from hen liver nuclei. Maximal incorporation of the ADP-ribose moiety from NAD into the L-type pyruvate kinase was 0.98 mol/mol of subunit. The Km values for NAD and L-type pyruvate kinase were 0.17 mM and 9.7 microM, respectively. ADP-ribosylation of the L-type pyruvate kinase resulted in suppression of the subsequent phosphorylation catalyzed by cAMP-dependent protein kinase. The ADP-ribosylation-induced suppression of phosphorylation of the L-type pyruvate kinase also resulted in suppression of the phosphorylation-induced inactivation. Amino acid analysis, after exhaustive sequential digestion of ADP-ribosyl-L-type pyruvate kinase with pepsin, aminopeptidase M and carboxy-peptidase B showed arginine to be the ADP ribose-accepting amino acid. These results together with finding of the ADP ribosyltransferase activity in mammalian liver cytosol (Moss, J. and Stanley, S.J. (1981) J. Biol. Chem. 256, 7830-7833) suggest that ADP-ribosylation may participate in the regulation of the L-type pyruvate kinase activity through changes in the rate of phosphorylation. PMID- 3349110 TI - Internal models and intermittency: a theoretical account of human tracking behavior. AB - This paper concerns the use of tracking studies to test a theoretical account of the information processing performed by the human CNS during control of movement. The theory provides a bridge between studies of reaction time and continuous tracking. It is proposed that the human CNS includes neuronal circuitry to compute inverse internal models of the multiple input, multiple output, dynamic, non-linear relationships between outgoing motor commands and their resulting perceptual consequences. The inverse internal models are employed during movement execution to transform preplanned trajectories of desired perceptual consequences into appropriate outgoing motor commands to achieve them. A finite interval of time is required by the CNS to preplan the desired perceptual consequences of a movement and it does not commence planning a new movement until planning of the old one has been completed. This behavior introduces intermittency into the planning of movements. In this paper we show that the gain and phase frequency response characteristics of the human operator in a visual pursuit tracking task can be derived theoretically from these assumptions. By incorporating the effects of internal model inaccuracy and of speed-accuracy trade-off in performance, it is shown that various aspects of experimentally measured tracking behavior can be accounted for. PMID- 3349111 TI - Stochastic prediction in pursuit tracking: an experimental test of adaptive model theory. AB - In this paper we test the proposition that in pursuit tracking, subjects compute stochastic (statistical) models of the temporal variations in position of the target and use these models to forecast target position for at least a response time interval into the future. A computer simulation of a human operator employing stochastic model prediction of target position is used to generate a synthetic pursuit tracking response signal. Actual pursuit tracking response signals are measured from 10 normal subjects using the same stimulus signal. Cross correlation and spectral analysis are employed to compute gain and phase frequency response characteristics for both synthetic and actual tracking data. The similarity of the gain and phase curves for synthetic and actual data provides compelling evidence in support of the proposition. PMID- 3349112 TI - Kinetics of human cone photopigments explained with a Rushton-Henry model. AB - Densitrometric measurements of the regeneration of cone visual photopigments have shown effects that cannot be explained by the existing quantitative models. Regeneration from a fully bleached state seems to depend on how this state has been reached and the shape of the regeneration curve cannot be produced by a first order reaction. Rushton and Henry (1968) proposed a store of 11-cis-retinal to explain rapid regeneration after a short bleach. We elaborated this idea into a quantitative model. Regeneration after three different bleach histories and steady state behaviour of the pigments was measured using the Utrecht densitometer. The Rushton-Henry model gives a good fit to the data and is clearly superior to the classical Rushton model in describing densitometric measurements. PMID- 3349113 TI - Stability and attractivity in associative memory networks. AB - We focus on stable and attractive states in a network having two-state neuron like elements. We calculate the connection matrix which guarantees the stability and the strongest attractivity of p memorized patterns. We present an analytical evaluation of the patterns' attractivity. These results are illustrated by some computer simulations. PMID- 3349114 TI - A synergetic theory of environmentally-specified and learned patterns of movement coordination. I. Relative phase dynamics. AB - This paper outlines and applies a synergetic strategy to the coordination of human rhythmical movement. It extends earlier empirical and theoretical work to include the influence of specific environmental information and of memory on the dynamics of the collective variables (order parameters) that characterize the coordination patterns. Key ideas concern cooperative and competitive influences on the collective dynamics. Recent experiments on environmentally specified and learned rhythmic movement patterns are modeled explicitly on the level of the collective variable, relative phase. New predictions are presented and research directions proposed that follow directly from the present theoretical approach. PMID- 3349116 TI - Fitting mathematical functions to joint kinematics during stepping: implications for motor control. AB - The present study extends past work on modeling and control of stepping. The relationship between joint space kinematic data and routine motor control (i.e., open loop) during human stepping is investigated. A model of open loop stepping control using joint kinematics is described. Different functional approximations are employed to simulate experimental joint kinematic data collected on a subject stepping repeatedly over an obstacle. Results indicate that joint kinematics can be characterized by a small number of functions yielding a simple analytical description of open loop motor control. The different basis functions used and their associated coefficients reflected the qualitative behavior of joint trajectories thus allowing flexibility in the formulation of system kinematics. This approach provides a tool to study movement pathologies and movement development by identifying the basis functions governing the kinematics of motion and their associated coefficients. The model presented here is helpful in studying the segmentation of multiarticular movements into their elementary components by analytically modeling the discrete organization of motor behavior. PMID- 3349115 TI - A synergetic theory of environmentally-specified and learned patterns of movement coordination. II. Component oscillator dynamics. AB - Rhythmic movement patterns have served as a model case for developing a synergetic theory of biological coordination. In part I of this work we extended the approach to environmentally-specified and learned movement patterns on the level of the collective variable relative phase. Here we show that an identical strategy may be applied to the same problem at the level of the component oscillators. Coordinative patterns and their dynamics are derived from the coupled component dynamics and their interaction with the environment. Thus, behavioral patterns are shown to arise in a purely self-organized fashion. New directions for further research (e.g. dynamics of action-perception systems) follow from the oscillator theory. Finally the relationship between our approach and other kinds of analyses of temporal order (e.g. phase resetting) is addressed. PMID- 3349117 TI - Staphylococcal adhesion to collagen in intra-articular sepsis. AB - Ultrastructural studies of the cartilaginous articular surfaces of human and rabbit joints have shown that cartilage is the target substratum for adhesion by Staphylococcus aureus, leading to intra-articular sepsis. Transmission and scanning electron microscope studies demonstrated bacteria in intimate contact with acellular cartilage matrix surfaces, particularly with collagen fibres. Certain strains of Staphylococcus aureus used in these experiments reveal a high binding capacity to collagen that is derived from a cartilage matrix. These studies indicate that the pathogenesis of intra-articular sepsis is based on the ability of certain strains of staphylococci to bind preferentially to a cartilage matrix. PMID- 3349118 TI - Deposition of endothelial fibronectin on polymeric surfaces. AB - Cellular fibronectin is deposited on tissue culture polystyrene during the adhesion and spreading of cultured human endothelial cells (HEC). Following the seeding of HEC upon this polymer, larger amounts of fibronectin are deposited as both cell density and incubation time increase. Our results indicate that the ability to deposit cellular fibronectin onto a polymeric surface is a condition for the spreading and proliferation of HEC. PMID- 3349119 TI - Protein adsorption at the interface between charged polymer substrata and migrating osteoblasts. AB - The in vitro migratory morphology of neonate rat calvarial osteoblasts on positively or negatively-charged polymer substrata was observed using scanning (SEM) and transmission electron microscopy (TEM). Proteins adsorbed from the culture medium onto these charged substrata were desorbed using 2% SDS and separated using polyacrylamide gel electrophoresis (PAGE). The charge sign of the substrata affected both protein adsorption and osteoblast migratory morphology. Cells flattened and adapted so closely to positively-charged substrata that the ventral cell membrane could not be distinguished at TEM. On negatively-charged substrata the ventral cell membrane was readily visible, with only focal areas of close contact with the substratum. The depth of the ventral extracellular space varied with the surface charge-carrier species on the negative substrata. Two desorbed protein fractions (MW 220 and 30 kDaltons, respectively) were correlated with osteoblast spreading on positive and negatively-charged surfaces respectively. Another protein fraction was uniquely present on PAGE profiles desorbed from negatively-charged substrata. It was concluded that the migratory morphology of osteoblasts was influenced via the intermediary of specifically adsorbed proteins. PMID- 3349120 TI - Albumin adsorption on alkyl chain derivatized polyurethanes. II. The effect of alkyl chain length. AB - Linear alkyl chains containing 2, 10 and 18 carbon atoms were grafted to 10% of the urethane nitrogens in a polyether-polyurethane. The polyurethane was synthesized from methylene bis(p-phenyl isocyanate), 1,4-butanediol, and polytetramethylene oxide of 1000 molecular weight in a molar ratio of 3/2/1. Fourier transform infrared spectroscopy and attenuated total reflectance optics were used to study the adsorption of 5.0 mg/ml human serum albumin (HSA) at 37 degrees C to the derivatized and non-derivatized polymers. Both delipidized HSA and HSA containing 6.5 mol stearic acid per mol of albumin were used to study the effect of chain length upon the initial adsorption rate, the total amount adsorbed in 1 h, and the desorption rate. The initial adsorption rates revealed that non-specific adsorption was similar upon all four polymers. An increase in initial adsorption rate upon the C-18 derivatized polymer was attributed to a specific binding interaction between the HSA and the grafted alkyl chains. The conformational stability of the HSA also affected the adsorption rate. The total amount adsorbed after 1 h decreased as the alkyl chain length increased from 2 to 18 methylene groups. The desorption rate decreased in magnitude as the alkyl chain length increased from C-2 to C-18. These results support a hypothesis that alkyl chain length influences the interaction between albumin and an alkylated polymer system. PMID- 3349121 TI - Adsorption of thrombin from buffer and modified plasma to polystyrene resins containing sulphonate and sulphamide arginyl methyl ester groups. AB - The adsorption of albumin and thrombin to insoluble modified polystyrene resins bearing sulphonate (PSSO3) and L-arginyl methyl ester groups (PAOM) was investigated in both purified and plasma systems. Radioiodinated proteins were used to follow adsorption in a 'minicolumn' experiment. Albumin adsorption was found to follow the Langmuir model and specific surface areas of the various resins were evaluated from plateau albumin adsorption data. The adsorption isotherms of thrombin both in buffer and in antithrombin III/fibrinogen-free plasma were also found to be Langmuir-like, and the quantities adsorbed at the isotherm plateaux are in the monolayer range. Analysis of the isotherms at 4 degrees and 37 degrees C for the purified system shows that adsorption is endothermic. Adsorption capacities in plasma remain high (30-50% of those in the purified system) despite competition from the other plasma proteins. These data confirm the strong affinity and selectivity of these resins for thrombin. PMID- 3349122 TI - Quantitative analysis of immunological reactions on silicon surfaces by multiple angle Brewster angle reflectometry. AB - An optical biosensing instrument has been developed for the quantitative analysis of immunological reactions on biochemically sensitized surfaces. It is based on the measurement of reflectance changes of polarized laser light incident on high refractive index substrates at angles close to the pseudo-Brewster angle. Multiple-angle Brewster angle reflectometry (MABAR) has been used to investigate the binding of anti-human serum albumin (a-HSA) to human serum albumin (HSA) coated silicon surfaces. The concentration dependence and reaction kinetics of antibody-antigen complex formation have been studied using red and green He-Ne laser light. A significant increase in sensitivity has been observed with green light. PMID- 3349124 TI - Adsorption of enzymes at the solid-liquid interface. I. Trypsin on polystyrene latex. AB - The enzyme, trypsin, has been used to study conformational changes which occur when protein adsorption onto well-characterized, emulsifier-free, polystyrene latex surface takes place. The adsorption isotherm is of the high affinity, Langmuirian type with plateau adsorption of trypsin of 2.8 mg m-2. The enzymic activity of adsorbed trypsin to low molecular weight substrate is found to decrease as the surface coverage decreases indicating that 'spreading' or unfolding of the native protein conformation, with consequent loss of enzymic activity, occurs. On the close packed surface such 'spreading' is inhibited by steric factors. The view that protein adsorption onto hydrophobic surfaces is dominated by the entropy gain due to protein unfolding to maximize hydrophobic interactions is thus supported. PMID- 3349123 TI - Control and isotopic quantification of affinity of antithrombin III for heparin like surfaces. AB - Heparin-like materials, characterized by a defined superficial density of functional groups which activate antithrombin III (AT III), when in contact with blood specifically inhibit thrombin as soon as it appears. This paper describes an isotopic method to estimate this density and to visualize the distribution of the affinity sites concerned, both directly with AT III labelled with 125Iodine and indirectly with an anti AT III monoclonal antibody labelled with 111Indium. PMID- 3349125 TI - Hollow implants in soft tissues allowing quantitative studies of cells and fluid at the implant interface. AB - In order to study the early cellular response in the fluid phase found close to implants in soft tissues, an experimental method using a hollow implant was developed. The fluid present in an interior chamber communicating with the exterior of the implant was analysed. Polymorphonuclear granulocytes (PMNGs) were predominant during the study (1-9 days). In titanium implants a slight increase in cell numbers with time was noted, whereas in polytetrafluoroethylene (PTFE) implants, a sharp increase in cell numbers was observed. Preliminary studies showed that sufficient amounts of fluid and cells could be retrieved for analysis of protein composition and inflammatory cell activation. PMID- 3349126 TI - Behaviour of fibroblasts and epidermal cells cultivated on analogues of extracellular matrix. AB - A porous collagen sponge can be used for supporting epidermal cells and fibroblasts in order to manufacture an artificial skin. Fibroblasts were grown on analogues of extracellular matrix containing collagen and glycosaminoglycans and/or glycoproteins. Cell replication, and also infiltration of fibroblasts, were enhanced by the presence of hyaluronic acid and/or fibronectin. Epidermal cells grown on a collagen sponge have been characterized by microscopic observations. Epidermal cells on the surface of the sponge showed an incomplete differentiation in comparison to normal skin; clumps of epidermal cells were found in the interior of the sponge. Epidermal cell replication was enhanced in the presence of collagen sponge seeded with fibroblasts. PMID- 3349128 TI - Raman spectroscopy of cytoplasmic muscle fiber proteins. Orientational order. AB - The polarized Raman spectra of glycerinated and intact single muscle fibers of the giant barnacle were obtained. These spectra show that the conformation sensitive amide I, amide III, and C-C stretching vibrations give Raman bands that are stronger when the electric field of both the incident and scattered radiation is parallel to the fiber axis (Izz). The detailed analysis of the amide I band by curve fitting shows that approximately 50% of the alpha-helical segments of the contractile proteins are oriented along the fiber axis, which is in good agreement with the conformation and composition of muscle fiber proteins. Difference Raman spectroscopy was also used to highlight the Raman bands attributed to the oriented segments of the alpha-helical proteins. The difference spectrum, which is very similar to the spectrum of tropomyosin, displays amide I and amide III bands at 1,645 and 1,310 cm-1, respectively, the bandwidth of the amide I line being characteristic of a highly alpha-helical biopolymer with a small dispersion of dihedral angles. A small dichroic effect was also observed for the band due to the CH2 bending mode at 1,450 cm-1 and on the 1,340 cm-1 band. In the C-C stretching mode region, two bands were detected at 902 and 938 cm-1 and are both assigned to the alpha-helical conformation. PMID- 3349127 TI - Clots of beta-fibrin. Viscoelastic properties, temperature dependence of elasticity, and interaction with fibrinogen-binding tetrapeptides. AB - Clots of human beta-fibrin, in which only (or predominantly) the B fibrinopeptide is released, were formed at 14 degrees C by copperhead venom procoagulant enzyme (CVE or venzyme), at pH 8.5, ionic strength 0.45. The shear modulus of elasticity increased slowly and after several days attained a constant value, which was lower than those of alpha-fibrin or alpha beta-fibrin under the same conditions. Before studying the temperature dependence of elasticity, the CVE was then inhibited by introducing phenyl methyl sulfonyl chloride (PMSF) by diffusion. With increasing temperature, the modulus decreased progressively from 5 degrees C to nearly zero at 35 degrees and was essentially reversible with temperature change; recovery of elasticity after change from 34.5 degrees to 14 degrees required approximately 2 d but was considerably faster than the initial buildup of elasticity by CVE at 14 degrees. Creep and creep recovery measurements on unligated clots showed creep rates and irrecoverable deformation that were similar in magnitude to those of alpha-fibrin clots formed with batroxobin and much larger than those of alpha beta-fibrin clots formed with thrombin, under the same conditions. During creep and creep recovery, the differential modulus or compliance remained constant, showing that there was no permanent structural damage, and if network strands are severed in slow flow, they must rejoin in new configurations. Introduction (by diffusion) of the tetrapeptides Gly-His-Arg-Pro (GHRP) and Gly-Pro-Arg-Pro (GPRP), which resemble the B and A binding sites on the E domain of fibrin respectively, reduced the shear modulus and increased the creep rate of beta-fibrin clots to an extent similar to the effect of GPRP on alpha beta-fibrin, much more than that of GHRP on alpha beta-fibrin, but much less than that of GPRP on a-fibrin. A ligated beta-fibrin clot formed with Factor XIIIa (in which the activating thrombin had been neutralized by hirudin) showed essentially perfect elastic behavior, with no creep and with complete recovery after removal of stress, and was inert to GHRP. PMID- 3349129 TI - Planar bilayer membranes made from phospholipid monolayers form by a thinning process. AB - We investigated the manner in which planar phospholipid membranes form when monolayers are sequentially raised. Simultaneous electrical and optical recordings showed that initially a thick film forms, and the capacitance of the film increases with the same time course as the observed thinning. The diameter of fully thinned membranes varies from membrane to membrane and a torus is readily observed. The frequency-dependent admittance of the membrane was measured using a wide-bandwidth voltage clamp whose frequency response is essentially independent of capacitative load. The membrane capacitance dominates the total admittance and the membrane dielectric is not lossy. The specific capacitance of membranes of several mixtures was measured. A schematic diagram of the formation of these membranes is presented. PMID- 3349131 TI - On the elasticity of cytoskeletal networks. AB - Models relating to the gelation and elasticity of complex cytoskeletal networks are formulated and investigated. Kinetic equations for reversible elongation of nucleated actin filaments are analyzed when the filaments are acted upon by capping proteins and cross-linking factors. Analytical expressions are obtained that relate the low frequency elastic shear modulus of a network, G, to chain growth kinetics, the number of nucleation sites, monomer concentration, and the amount of capping and cross-linking protein. Elasticity curves that relate G to such factors as the association constant for cross-linking are derived and then used to determine solation-gelation phase contours. PMID- 3349130 TI - Biophysical evidence that light adaptation in Limulus photoreceptors is due to a negative feedback. AB - The steady-state stimulus-response curve of the Limulus ventral photoreceptor comprises a linear portion followed by a less-than-unity power law dependence, which is maintained over at least 4 decades of intensity. This progressive desensitization corresponds to light adaptation. For flash stimulation of dark adapted cells, the stimulus-response curve again has an initial linear portion, but this is followed by a region of supralinearity before the curve saturates. In a previous article, we showed that the distribution of time integrals of the single-photon responses is consistent with a model of a single chain of first order reactions. Starting with such a model, we have looked at relevant elementary nonlinear biochemical mechanisms to determine which of them can modulate the enzymatic amplifications of the chain in such a way as to lead to these behaviors. We assume that each of the two phenomena, adaptation and supralinearity, derives from a single mechanism that acts on a single enzymatic stage. We then conclude that the adaptation must be a cooperative negative feedback, in which an accessory material activated by a late stage of the transduction chain acts cooperatively to inhibit an earlier enzymatic amplification. In Limulus, the number of molecules that cooperate is between 3 and 5. We were not able to discard any of the mechanisms tested for the supralinearity, except to say that they must act at a stage of the chain later than that on which the adaptive material acts. If we assume the conclusions of a previous work which shows that the supralinearity mechanism is active during the steady state, we can also conclude that the supralinearity stage must precede the stage that is the source of the adaptive material. PMID- 3349132 TI - Deuteron field-cycling relaxation spectroscopy and translational water diffusion in protein hydration shells. AB - The deuterated hydration shells of bovine serum (BSA) albumin, and purple membrane sheets have been studied by the aid of deuteron field-cycling relaxation spectroscopy. The deuteron Larmor frequency range was 10(3) to 10(8) Hz. The temperature and the water content has been varied. The data distinguish translational diffusion on the protein surface from macromolecular tumbling or exchange with free water. A theory well describing all dependences has been developed on this basis. All parameters have successfully been tested concerning consistency with other sources of information. The concept is considered as a major relaxation scheme determining, apart from cross-relaxation effects, the water proton relaxation in tissue. PMID- 3349133 TI - A theory of the symmetries of filamentous bacteriophages. AB - A mathematical model is presented which explains the symmetries observed for the protein coats of filamentous bacterial viruses. Three viruses (Ff, IKe, and If1) all have five-start helices with rotation angles of 36 degrees and axial translations of 16 A (Type I symmetry), and three other viruses (Pf1, Xf, and Pf3) all have one-start helices with rotation angles of approximately equal to 67 degrees and translations of approximately 3 A (Type II symmetry). The coat protein subunits in each group diverge from each other in amino acid sequence, and Type II viruses differ dramatically in DNA structure. Regardless of the differences, both Type I and Type II symmetry can be understood as direct, natural consequences of the close-packing of alpha-helical protein subunits. In our treatment, an alpha-helical subunit is modeled as consisting of two interconnected, flexible tubular segments that follow helical paths around the DNA, one in an inner layer and the other in an outer layer. The mathematical model is a set of algebraic equations describing the disposition of the flexible segments. Solutions are described by newly introduced symmetry indices and other parameters. An exhaustive survey over the range of indices has produced a library of all structures that are geometrically feasible within our modeling scheme. Solutions which correspond in their rotation angles to Type I and Type II viruses occur over large ranges of the parameter space. A few solutions with other symmetries are also allowed, and viruses with these symmetries may exist in nature. One solution to the set of equations, obtained without any recourse to the x-ray data, yields a calculated x-ray diffraction pattern for Pf1 which compares reasonably with experimental patterns. The close-packing geometry we have used helps explain the near constant linear mass density of known filamentous phages. Helicoid, rigid cylinder, and maximum entropy structure models proposed by others for Pf1 are reconciled with the flexible tube models and with one another. PMID- 3349134 TI - Differential polarization imaging. III. Theory confirmation. Patterns of polymerization of hemoglobin S in red blood sickle cells. AB - In this paper we test the predictions of the differential polarization imaging theory developed in the previous two papers. A characterization of the patterns of polymerization of hemoglobin in red blood cells from patients with sickle cell anemia is presented. This system was chosen because it is relatively easy to handle and because previous studies have been done on it. A differential polarization microscope designed and built in our laboratory was used to carry out this study. This microscope uses an image dissector camera, a photoelastic modulator, and a phase-lock amplifier. This design represents a substantial modification with respect to the instrumentation used in the previous results communicated on this system. Therefore, the results presented here also permit us to confirm the validity of our conclusions. On the basis of the differential polarization images obtained, models of the patterns of polymerization of the hemoglobin S inside the sickle cells are proposed and their M12 and regular images are calculated by the theory. Good agreement between those models and the experimental systems is found, as well as with the results previously reported. PMID- 3349135 TI - The attractive forces between polar lipid bilayers. AB - Long-range attractive forces between lipid bilayers are not well described by the Lifshitz theory of Van der Waals forces between macroscopic media. It is shown that when correlations between polar headgroups are taken into account, the predicted forces take a qualitatively different form consistent with the measured data. PMID- 3349136 TI - Protein folding observed by time-resolved synchrotron x-ray scattering. A feasibility study. AB - A solution to the "protein folding" problem, the successful prediction of tertiary and quaternary protein structure from amino acid or gene sequence, would be a major advance in biology and biotechnology. Knowledge of any intermediate structure between fully unwound and folded would aid folding calculations. The use of high intensity synchrotron x-rays from the SUNY X21 beamline at National Synchrotron Light Source has been investigated as a probe of structural changes during protein folding and unfolding in solution. A temperature jump apparatus was used to study thermally-induced folding and unfolding. Scattering of solutions of myoglobin in the angular range 20 = 1-50 mrad. was measured during temperature jumps between 26 and 76 degrees C. There are clear signs of time/temperature-dependent structural changes, in the small angle region, consistent with those from other equilibrium techniques. Analysis indicates that this experimental technique can be extended to the higher angle region where theoretical calculations indicate more detailed structural information, for example when alpha-helix formation, is present. PMID- 3349137 TI - A time-resolved spectral study of the K and KL intermediates of bacteriorhodopsin. AB - Nanosecond time-resolved absorption measurements on the photolysis products of bacteriorhodopsin (BR) in intact membranes are reported. At room temperature in fluid solution a single intermediate (KL) is seen 10 ns after excitation. Both spectral and kinetic results are consistent with the KL intermediate converting to the L intermediate by a single first order reaction. The observed temperature dependent rate has the Arrhenius parameters: Ea = 10.5 kcal/mol, A = 5 x 10(13) s 1. The precursor to the KL intermediate is also observed. Its spectral character is consistent with the K intermediate which has been previously reported. The current data is consistent with a linear sequence in the BR photocycle for K, KL, and L in room temperature fluid solution. Differences in the spectral characteristics of the K intermediates described here and elsewhere are discussed in terms of differences in the microenvironment around the retinal moiety and the affect this may have on the conformation of the chromophore. PMID- 3349138 TI - [Synchronous blood flow changes in the 2 common carotid arteries of the cat during systemic pressor reaction to catecholamine administration]. PMID- 3349139 TI - [Increased level of immunoreactive opioid peptides in the brain and adrenals of rats as affected by adaptation to physical loading]. AB - The effect of long-term (7 weeks) swimming training on the content of beta endorphin, met- and leu-enkephalins in various brain regions and adrenal glands has been studied in Wistar rats. It has been shown that the adaptation to exercise induced an increase in the content of opioid peptides in most of the brain regions and in adrenal glands. This increase in the level of opioid peptides seems to play an important role in the increase of the resistance to stress. PMID- 3349140 TI - [Dependence of skeletal muscle fatigue on the membrane polarization of the different types of muscle fibers in tourniquet shock]. AB - Fatigue, polarization level and excitability of striated muscle fibers from ischemia zone were studied on experimental rats under the tourniquet shock. It was established that violation-mediated contraction and fatigue of skeletal muscle was associated with a decrease in a number of muscle fibers with high level of MPP. The article discussed the mechanisms of fatigue and depolarization of muscle fibres in tourniquet shock. PMID- 3349141 TI - [Amino acid composition of the lymph and blood in fever reactions of different durations]. AB - The amino acid composition of the thoracic duct lymph and blood following fever reactions (FR) of various duration has been studied in the experiments on rabbits. The experiments have shown that some changes in protein metabolism in FR are primarily manifested in amino acid lymph composition. Irrespective of FR duration the amino acid content in the lymph almost always increases, which confirms the opinion concerning catabolic process predominance in protein metabolism during FR. The lack of "cumulative" conditions in the blood, amino acid dilution in the large volume of the circulating blood, as well as the increase of vascular permeability during FR cause less marked increase in amino acid content in the blood than in the lymph. PMID- 3349142 TI - [Demonstration of postural asymmetry factors in a hypophyseal tissue culture as affected by the cerebrospinal fluid of cats with unilateral damage to the hemispheric cortex]. AB - It has been experimentally established that special hypophysiotropic factors- precursors of pose asymmetry factors (PAF) are found in the cerebrospinal fluid of donor animals with cortical lesions during the first postoperative hours. These factors, being specific for the location of the cortical lesion in donor animals, appear to be hypophysiotropic peptide substances inducing the production of corresponding PAF by hypophysial cells. The production of certain PAF by the rat hypophysial tissue cultures under the influence of cerebrospinal fluid from cats gives evidence in favour of species nonspecificity of PAF inductors. PMID- 3349143 TI - [Homeostatic role of calcitonin antibodies in calcium metabolism in experimental diabetes mellitus]. AB - In experimental alloxan diabetes marked hypocalcemia and hyperglycemia are observed in the blood of rats during the acute period of the disease (from 1.5 to 2 months). After 2.5-3.5 months of diabetes calcium level reaches the upper normal limit. Simultaneously, antibodies to calcitonin appear. It is quite likely that excessive calcitonin secretion, leading to hypocalcemia, decreased insulin secretion and hyperglycemia take place in the acute stage of diabetes. When diabetes persists the antibodies to calcitonin which reveal a homeostatic reaction blocking the excess of calcitonin appear. This normalizes the level of calcium in the blood and prevents the further increase in the blood sugar level. PMID- 3349145 TI - [Species differences in the behavioral effects of cerulein--an agonist of the receptors of the octapeptide cholecystokinin--in white mice and rats]. AB - It has been shown in the behavioural experiments that combined pretreatment with haloperidol (0.25 mg/kg) and caerulein (40 micrograms/kg), and to a lesser extent pretreatment with caerulein alone caused long-term reversal of amphetamine (2 mg/kg) induced hyperexcitability in rats. Administration of proglumide (50 mg/kg), an antagonist of CCK-8 receptors, did not reverse long-term antiamphetamine effect of caerulein. In mice pretreatment with caerulein (50 and 100 micrograms/kg) alone or in combination with haloperidol (0.25 mg/kg) caused hypersensitivity to the behavioural effect of amphetamine (3 mg/kg). Intraventricular (I ng), but not systemic (100-500 micrograms/kg) administration of caerulein selectively antagonized seizures in mice induced by intraventricular administration of quinolinic acid (5 micrograms) and N-methyl-D-aspartate (0.2 microgram). Pretreatment with proglumide (50 mg/kg) reversed the anticonvulsive effect of caerulein in mice. In rats, caerulein failed to affect the seizures caused by intraventricular administration of quinolinic acid. The results of the present study demonstrate the existence of obvious interspecies differences in the behavioural effects of caerulein, the agonist of CCK-8 receptors, in mice and rats. PMID- 3349144 TI - [Effect of danazol on the function of the estrogen and progesterone receptor systems of the human endometrium]. AB - Quantity of estrogen- and progesterone-specific binding sites was measured in endometrial tissues of 10 females treated with danazol during 3 month in a dose of 400 mg per day after surgical treatment for endometriosis. It was demonstrated that the amount of estrogen receptors in endometrium of the patients was the same as in endometrial tissue of healthy females but the quantity of nuclear progesterone receptors was markedly increased. PMID- 3349147 TI - [Effect of aminazine and triftazin on the synaptosome membranes of the rat cerebral cortex]. AB - Fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and pyrene were employed in studying the effect of aminazine and triftazin versus that of imipramine on microviscosity of rat brain cortex synaptosomal membranes. Unlike imipramine, the neuroleptics decrease microviscosity of membrane's lipid bilayer. All drugs decrease fluorescence of endogenous tryptophan, but fail to change fluorescence of L-tryptophan in the solution. It is concluded that neuroleptics induce conformational perturbations in membrane-bound proteins modifying microviscosity of lipid bilayer whereas imipramine changes the surface electric charge of lipid bilayer of synaptosomal membranes. PMID- 3349146 TI - [Changes in the antioxidative activity and phospholipid composition of the erythrocytes in neurosis patients as affected by fenazepam]. PMID- 3349148 TI - [Suppressive effect of the blast cells of AKR strain mice on antibody formation in vivo and lymphocyte proliferation in vitro]. AB - Blast cells obtained from the "erythropoietic spleen" of FG-stimulated young mice and cells accumulating in the spleens of preleukemic AKR mice have a marked suppressive effect on spontaneous and mitogen-induced proliferation of young mouse splenocytes in vitro and suppress the development of humoral immune response in immunized recipients during syngeneic transfer in vivo. Some disturbances in erythron system in preleukemic AKR mice manifested in the accumulation of immature erythroid precursors which are suppressors of immunocompetent lymphocytes are suggested to be a pathogenetic link in the development of leukemia. PMID- 3349149 TI - [Topological DNA heterogeneity in the nucleoids of human leukocytes]. PMID- 3349150 TI - [Sensitivity of the splenic cells of different mouse strains to the antiproliferative action of alkylating compounds]. AB - A method of quantitative evaluation of lymphocytes' sensitivity to the antiproliferative effect of the alkylating drugs has been developed. Chlorbutin, mafosfamide (Asta Z 7654) and "active" metabolites of cyclophosphamide were studied. This research allowed to distinguish more sensitive strains (DBA/2 and C57BL/6) and those with low sensitivity (BALB/c and CC57BR). These differences do not depend on proliferation reaction, neither on the type of alkylating drugs nor haplotypes H-2. PMID- 3349151 TI - [Content of cytochrome P-450 and its induction capacity in primary liver tumors in rats]. AB - The content of cytochrome P-450 has been measured in primary hepatomas induced by diethylnitrosamine. As a rule, the enzyme content in hepatomas was decreased, as compared to normal liver and tumor-affected liver, but some hepatomas contained cytochrome P-450 in greater amount than normal tissue. Aroclor 1254 induced an increase in cytochrome P-450 content, which was identical in hepatomas, normal liver and tumor-affected liver. The dependence of hepatoma morphology on cytochrome P-450 content was not detected. PMID- 3349152 TI - [Secretion of prostaglandin type E (PGE) by tumor cells of Syrian hamsters in in vitro contact with natural killers]. AB - The ability of Syrian hamster tumor cells of the same origin but with different degrees of malignancy to secrete prostaglandin E (PGE) was studied following their in vitro contact with Syrian hamster natural killer cells (NK cells). Syrian hamster NK cells were shown to lose significantly cytotoxic activity after their contact with malignant tumor cells. Short-term in vitro contact of malignant tumor cells with human and Syrian hamster NK cells resulted in a rapid PGE secretion into the culturing medium. PGE was determined in the culturing medium, using the biological test, described in the paper, or direct radioimmunoassay. No PGE secretion was observed after the treatment of tumor cells with indomethacin. It is assumed that PGE secretion by malignant tumor cells is one of the mechanisms of their protection against natural killer cells. PMID- 3349153 TI - [The relation of calcium biorhythms to helio-geophysical factors]. AB - In the course of 64 days the calcium concentration was daily determined in the blood serum of 6 male rabbits. From the first to the 32nd day round of research the rabbits were intact, and from the 33rd to 64th day round they were singularly immunized with human antimeasles gamma-globulin. With the help of the original algorithm the monthly rhythms' hierarchy was determined in the individual calcium dynamics as well as in the dynamics of synchronously measured solar activity indexes. It is discovered that singular immunization turned the 10-day calcium biorhythms' phase in reverse direction failing to affect the mean level, period length and the amplitude of them. Normal half-month calcium biorhythms stood in an anti-phase position to the analogous Wolf numbers' change and solar radio emanation in the wave of 2800 MHz rhythms. PMID- 3349154 TI - [Preparation of liver cultures from human embryos]. AB - The cultures were obtained from 9-12-week-old human embryonic liver. 24-36 hours after seeding the cultures containing a multilayer focus of adhesion and a monolayer growth zone were formed. The growth zone contained hepatocytes with bile pigment granules in the cytoplasm. The formation of culture monolayer coincided with the elimination of hemopoietic cells. PMID- 3349155 TI - [Functional restructurings of the mononuclear phagocyte system in experimental liver cirrhosis]. AB - In rats with CCl4-induced liver cirrhosis the clearance rate of colloid carbon particles was more than 2 times lower than in control animals. Simultaneously the uptake capacity of liver Kupffer calls falls. The number of phagocytizing liver macrophages decreased. Along with the diminished functional activity of liver macrophages in cirrhotic liver, the total number of lung and spleen macrophages increased 1.5-fold, with their uptake capacity increasing 10- and 3-fold, respectively. The nitroblue tetrazolium dye reduction and methacrylate particles uptake by alveolar macrophages in vitro rises. The liver, lung, spleen and peritoneal macrophages during liver fibrosis become less sensitive to zymosan stimulation. The incidence of zymosan-induced liver infiltrates decreases 50 fold, while in the lungs they do not develop at all. Such a decreased macrophage reactivity may be closely linked with progressing, poorly reversible liver fibrosis. PMID- 3349156 TI - [Seasonal dynamics of adrenal mineralocorticoid function in rats]. AB - Seasonal peculiarities of adrenal mineralocorticoid function and some aspects of its regulation have been studied in experiments on male Wistar rats. It has been found that changes in aldosteronemia and aldosteronurea were maximum in spring and minimum in summer--autumn period. The highest indices of aldosterone metabolic clearance from plasma were observed in winter with the following progressing decrease and a small increase in autumn. The diagram of melatonin content in the epiphysis of experimental rats was the same. Hypokinesia attenuated aldosteronurea during all the investigation periods, preserving the character of aldosterone secretion year curve. PRA level changed irrespective of aldosterone levels in plasma and urea. It has been concluded that a certain stability of mineralocorticoid adrenal function seasonal rhythms has different regulating effects. PMID- 3349157 TI - [Development of magnocellular neurosecretory neurons in embryonic hypothalamic tissue transplanted into the cavity of the 3d cerebral ventricle of adult rats]. AB - Magnocellular neurosecretory cell (MSC) ontogenesis was comparatively assessed in normal rat hypothalamus and in fetal hypothalamic tissue transplanted into the third ventricle of the adult rat brain. 3H-thymidine uptake has shown that the time of origin of NSC in grafted tissue and supraoptic nucleus of normal rat fetuses was similar. NSC pericarions in grafts were well developed and contained neurosecretory material (NSM). Nuclear and nucleolar volumes did not differ from those in adult animals. Water deprivation was followed by a significant increase in nuclear and nucleolar volumes and NSM content in pericarions of grafted tissue, which suggests that raised synthetic activity was not accompanied by an increased NSM release. It is concluded that proliferation and specific differentiation of NSC precursor cells are invariably determined by genetic factors. The origin of neurosecretory nuclei and their specific connections is considerably influenced by conditions of tissue surroundings. PMID- 3349158 TI - [Characteristics of the secretory activity of the respiratory cells of mouse lungs after partial chemical sympathectomy]. AB - Partial "sympathectomy" in the neonatal BALB mice was achieved by the treatment with guanethidine. The number of neurons in the stellate ganglion decreased to 20% of the control values and remained constant throughout the subsequent period of 1 month. Partial "chemical sympathectomy" did not affect the postnatal growth and development of the lungs. Partial "chemical sympathectomy" significantly increased the number of secreting cells in bronchiolar and alveolar regions. Secretory activity of the alveolocyte population, type two, synthetizing and secreting surfactant also increased. It has been concluded that the partial "chemical sympathectomy" stimulated the alveolar surfactant secretion. PMID- 3349159 TI - [Morphology of the cellular growth of organ cultures of fetal crystalline lens]. AB - 144 crystalline lenses of swine fetuses, 10 to 20 Mm long, were organ-cultured for up to 42 days in Eagles medium or DMEM in combination with 6% or 20% fetal calf serum. The types of cells detected included epithelioid and infiltrating cells (in 11.1% of lenses), fibroblast-like cells (in 20.8% of lenses) and vesicular cells (in 49.3% of lenses). These cell types characteristic of pathological (cataract-affected) lenses in vivo are absent in normal lenses. According to the data obtained, long-term organ culture of the fetal eye lens may be used as an experimental model of cataractogenesis. PMID- 3349161 TI - [Changes in the calcium metabolism of cerebral cortical structures in anoxia in vitro]. AB - Changes in membrane-bound calcium (Ca2+(b)) content in the brain cortex membrane structures were studied on subcellular fractions (synaptosomes, microsomes, mitochondria) during in vitro anoxia. The changes in Ca2+ content in hydrophobic domains of intracellular membranes were assessed, using chlorotetracycline fluorescent probe. It has been found that membranes of different neuronal compartments are not equally vulnerable to anoxia. A decrease in Ca2+9(b) content in response to anoxia occurs in synaptosomes and microsomes much sooner than in mitochondria. Therefore, Ca2+ release from intracellular membrane compartments, preceding the massive inward flow of extracellular Ca2+, seems to be one of those mechanisms initiating a complex range of intracellular reactions to disturbed oxygen supply in brain cortex neurons. PMID- 3349160 TI - [Neurohistochemical study of intestinal innervation in experimental diffuse peritonitis]. AB - In rats with diffuse peritonitis obtained by intraabdominal administration of a 10% fecal suspension (0.8 ml X 100g) neurohistochemical methods were used to study the adrenergic and cholinergic innervation of muscular membrane of the small and large intestine. It is shown that the disturbance of cholinergic innervation comes along with the intestinal paresis. Adrenergic innervation, represented by separate bundles, is found to be slightly affected. PMID- 3349162 TI - [Action of cortical extracts of the left and right hemispheres on the recovery of conditioned reflex activity in rats after unilateral removal of the frontal cortex]. AB - The recovery of active avoidance conditioned reflex (AACR) was investigated after unilateral frontal cortex extirpation. Intraperitoneal injection of extracts from left or right brain cortex (1 mg/kg) of healthy rats (LE or RE) stimulated AACR recovery in animals with lobectomy on the same side. If RE was extracted 9 days after left side brain extirpation, i.e. during the period of the development of compensatory processes, its effect on AACR recovery was stronger in left-operated animals, while in right-operated animals it remained unchanged. PMID- 3349163 TI - [Role of the stromal microenvironment in regulating bone marrow hemopoiesis under stress]. AB - The role of stromal microenvironment in bone marrow hemopoiesis during stress has been studied. The stimulation of functional activity of stromal cells, responsible for the transfer of hemopoiesis-inducing microenvironment has been found. The time required for the development of microenvironment coincide with the moment of T-lymphocyte appearance in the bone marrow. The induction of microenvironment preceded the development of hemopoiesis hyperplasia at the level of committed precursor cells of myelopoiesis and their more mature, morphologically differentiated progeny. PMID- 3349164 TI - [Participation of the cardiovascular neurons of the bulbar cardiovascular center in the adaptive reactions of the circulatory system during changes in the composition of inspired air]. AB - The experiments performed on rabbits have shown that with the inhalation of various gas mixtures the impulse activity of cardiovascular neurons in bulbar cardiovascular centre is changed. The most active are inserted cardiovascular neurons that are highly sensitive to O2 shortage and CO2 excess. It is believed that the experiments on Hering nerve severing indicate the possible development of reflex effects on hemodynamics during changes in inhaled gas composition produced from sinocarotid reflexogenic zone not only through bulbar respiratory neurons, but also through a system of inserted neurons of bulbar cardiovascular centre. PMID- 3349165 TI - [Dynamic changes in arylsulfatase activity in the initial period of acute focal myocardial ischemia in an experiment]. AB - The increase in arylsulphatase activity in the ischemic zone has been shown by histochemical method in progressing acute myocardial ischemia. The increase in the enzyme activity in a so-called "intact" zone was less marked. PMID- 3349166 TI - [Serotonin metabolism in thrombocytes and microvascular hemostasis in spontaneous arterial hypertension]. AB - Serotonin content and accumulation in platelets and its release from them, as well as changes in thrombus formation in mesenteric arterioles and venules of the small intestine have been investigated in control rats and rats with spontaneous hypertension (SHR). Serotonin accumulation in platelets was determined upon its incubation with platelets. Disodium ADP salt was used as an inductor of release. Laser-induced thrombosis was caused by microvessels exposure to impulse laser irradiation. The control animals revealed a significant difference between the initial serotonin platelet level and serotonin level upon incubation and release; in values, the values of basic thrombus-forming parameters were higher than in arterioles. In SHR there is a decrease in biogenic amine content in platelets, a depression in its accumulation and release, an increase in the time of thrombus growth, its size up to the separation of the first embolus and its length along the vascular wall. It is concluded that spontaneous hypertension is characterized by decreased functional activity of platelets and depressed resistance of arterioles and venules to thrombus formation. PMID- 3349167 TI - [Effect of the fever reaction on the kallikrein-kinin system of the lymph and blood]. AB - The dynamics of kallikrein-kinin system components in the lymph of thoracic duct and blood following fever reaction of various duration has been studied in the experiment on rabbits. The experiments have shown that in prolonged fever reaction there are qualitative disorders in kinin system components ratio indicative of break in the system of regulatory links, its exhaustion and transformation of the physiological reactions into the pathogenic ones. One may assume that changes in kallikrein-kinin system activity in body fluid are the links in the complex of pathogenic disorders in the organ and system functional activity during prolonged fever reaction. PMID- 3349168 TI - [Effect of dalargin on blood and lymph microcirculation]. AB - Dalargin (a synthetic analog of leu-enkephalin), when applied to the microvessel surface or administered intramuscularly at doses 0.004-40.0 micrograms/kg increased the permeability of the rat mesenteric microvascular wall and activated the lymph flow due to enhanced contraction of lymphatic microvascular wall and valves. Moreover, Dalargin evoked leukocyte migration from venules and activated the intestinal muscular contractions. PMID- 3349169 TI - [Biological activity of thymus preparations from sheep of various ages]. AB - Thymus active fractions from 3-year-old sheep were shown to cause immune response stimulation to sheep red blood cells in experimental immune deficiency in mice. The fraction from fetal lamb and sheep thymus was more active than that of mature animals in increasing immune rosette-formation in the lymph of central and peripheral organs of the immune deficient mice. All the preparations recovered the number of splenocytes in immune deficient mice. Therefore, thymus active fractions obtained from sheep at different stages of ontogenesis had a stimulating effect on cell proliferation and immunogenesis. PMID- 3349170 TI - [Immunomodulating action of myelopeptides in severe closed experimental craniocerebral injury in rats]. AB - An immunocorrective effect of myelopeptides (MP) isolated from pig bone marrow cell culture supernatant in the early posttraumatic period in rats with severe cranial injury has been assessed. MP administration prevented cellular devastation of thymus and bone marrow, as well as spleen hyperplasia. The most marked MP effect was observed within the first 24 h after its administration. MP affected the functional and migration properties of both the entire population of lymphoid cells and individual subpopulations. MP had a pronounced protective effect against Staph. aureus infection during cranial trauma. MP completely prevented the death of animals and reduced more than 3-fold Staph. aureus persistence in the organism of animals. Anti-stress and protective effects of MP open vast prospects for their therapeutic and preventive application in the clinical practice. PMID- 3349171 TI - [Heterogeneity of murine sarcoma cells for transplantability due to their different susceptibilities to the lytic action of macrophages]. AB - Sarcoma was induced in C57BL/6 mice with 20-methylcholanthrene. The sarcoma cells were found to be heterogeneous in their transplantability. The study of 9 clones distinct in this property has shown that heterogeneous transplantability was due to different susceptibility to lytic action of macrophages. PMID- 3349172 TI - [Human cervical cancer transplantable to athymic mice]. AB - Pregnancy in nude mice proved to be a favourable period for a successful human cervical tumor transplantation. This approach made it possible to obtain human cervical tumors, serially transplanted to nude mice. After several passages the tumor acquired the ability to be transplanted to nonpregnant female mice. The tumor retained a histological pattern of an original human tumor. PMID- 3349173 TI - [Cellular oncogene expression in human tumors transplantable to athymic mice]. AB - Expression of 3 cellular oncogenes among 7 ones under investigation is identified in the majority of 20 strains of human tumors, passaged in nude mice without significant specificity as far as the type of the tumor is concerned. The levels of the expression of these 3 oncogenes (c-myc, c-fos, c-ras) were higher than the ones in primary human tumors except for the human melanoma Mel-2 strain, where the expression of c-myb oncogene was identified. All the rest oncogenes (c-mos, B lym, c-sis, c-myb) showed no expression in human tumors of the examined strains. PMID- 3349174 TI - [The resonance nature of the dependence of epithelial lesions of the small intestine in mice on the interval between injections of an S-phase-specific agent -hydroxyurea]. AB - The dependence of the injury of murine small intestinal epithelium on the interval between multiple regular injections of hydroxyurea (HU) was investigated. Mice were injected 8 times with HU (5 mg per injection) in different experimental groups of animals, and the interval between injections varied from 6 to 19 hours. With the intervals between the injections close to 8 or 16.5 hours the resonance decrease of the injury was observed whereas the intervals of 6, 12 and 19 hours corresponded to maximum injury. PMID- 3349175 TI - [Effect of a food ration with a low-protein content on the processes of liver parenchyma recovery in rats after tetrachloromethane damage]. AB - Male Wistar rats weighing 190-200 g were fed a low protein diet. Atrophy of cytoplasm was observed after a 3-week malnutrition. In early periods of liver regeneration (6 hr after CCl4 poisoning), an increase in DNA synthesis was accompanied by an increase in summary concentration of organelle membranes. Though their ploidy was higher than in the control, volume of hepatocytes and summary area of organelles surface membrane was smaller than in standard diet. These data show a reduced capacity for realization of genetic program during the regeneration period in protein-deficient rats. PMID- 3349176 TI - [Seasonal fluctuations in the activity of stromal precursor cells of human bone marrow]. AB - The results of the cloning of fibroblastic colony-forming units (CFU-F) from the bone marrow of normal sites of the spongy bones were analysed in 250 orthopaedic patients. It has been shown that the activity of CFU-F was changing during a year. The number of negative results of CFU-F's cloning were 33%, 60% and 50% in March, April and October respectively. The absolute values of CFU-F cloning were lower in March and April than in other months. The seasonal changes in the activity of CFU-F in human bone marrow should be taken into consideration when studying the physiology and pathology of the bone and hemopoietic system, and in clinical practice. PMID- 3349177 TI - [Phase coordination of the rhythms of changes in solar activity and of the monthly biorhythms of altered cholesterol levels of the blood serum in rabbits]. AB - The concentration of total, free and bound cholesterol in the blood serum of 13 intact Chinchilla male rabbits was determined in two four-month experiments carried out in 1973-1974 and in 1984-1985 during a "minimum" phase of an 11-year solar activity cycle. A hierarchy of ten cholesterol biorhythms and solar activity rhythms were singled out on a computer, using an original algorithm, in the individual changes in cholesterol concentration in each rabbit and in changes in seven environmental indexes. A statistical stability of the frequency and phase of low-frequency cholesterol biorhythms and solar activity rhythms has been established within an 11-year period, the fluctuation amplitude of the indexes studied being, on the contrary, statistically unstable. PMID- 3349178 TI - [Dynamic immunological and cytochemical markers in the induced differentiation of the K-562 cell line]. AB - The possibility of TPA-induced differentiation of K-562 cell line was studied. Monoclonal antibodies against differentiating antigens of HAE erythroid lineage and against myelomonocytic ICO lineage raised in the USSR Cancer Research Centre were used. Changes in immunological and cytochemical indexes suggest that K-562 cell differentiation goes in the erythroid direction. The cells lost early differentiation and acquired late differentiation markers. PMID- 3349179 TI - [Synapses of the human brain in early prenatal ontogeny]. AB - Synaptogenesis in presumptive cerebral cortex was studied in 7-8 week human embryos by electron microscopy. The first synapses in the regions studied appeared in 7-week embryos. These synapses were detected only in the marginal zone of the developing human cerebral cortex, where they were localized on the somas and processes of the young Cajal-Retzius' neurons. A functional role of early embryonic synaptogenesis in the developing human cerebral cortex is suggested. PMID- 3349180 TI - [Ultrastructure of cardiomyocytes in the peri-infarct zone during the treatment of experimental myocardial infarct in rats using the hexapeptide dalargin]. AB - The experiments on white rats with induced myocardial infarction have studied the influence of dalargin on the infarction size and peri-infarction zone ultrastructure. 24 hours later the decrease in the infarction zone size was detected in rats who had received dalargin in a dose of 50 and 100 micrograms/kg. In the peri-infarction zone the increase in glycogen quantity, the lower degree of lipid infiltration, the increase in mitochondrial number and mitochondrial energy effectiveness coefficient were noted, as compared to control animals. Sarcolemma of cardiomyocytes from the peri-infarction zone in rats on dalargin was impermeable for colloidal lanthanum. The decrease in the infarction size under the effect of dalargin is explained by its influence on the survival of cardiomyocytes in the peri-infarction zone. PMID- 3349181 TI - [Function of the microcirculatory system during the long-term regression of the early stages of atherogenesis]. AB - Lipid metabolism, intestinal mesentery microcirculatory bed (MCB) and erythrocyte (E) morphology in arterial and venous blood were studied in rabbits with experimental atherosclerosis (the model of N. N. Anichkov) and its spontaneous regression. The interrelation was determined between lipid metabolism (LM), MCB structural and functional disorders and anomalous E form appearance, and to a lesser extent the atheromatosis of the aorta. Microcirculatory (MC) disorders disappeared 12 months later in the regression of the early stages of atherogenesis (after 2 months of diet). The generalized character of MC disorders in LM suggests the existence of a trend towards MC reconstitution in prolonged regression in different organs and tissues. Thus, LM correction at the early stages of the pathological process can be accompanied by the disappearance of MC disorders, which seems important for the prevention of atherosclerosis. PMID- 3349182 TI - [The mechanisms of reparative regeneration of venous endothelium]. AB - The reaction of endothelial cells of the inferior vena cava in response to freezing-induced lesions has been analysed in the experiments on 34 young adult Kyoto-Wistar normotensive rats. First the de-endothelialized surface is covered with flattened platelets and then, three days after surgery, the endothelium is restored as a result of migration and proliferation of endotheliocytes. The migrating endothelial cells removed the adhered platelets from de-endothelialized surface. The young endothelium was presented by a single layer of strongly elongated endothelial cells whose axis was parallel to the flow of blood. An immature endothelium is characterized by an increased number of endotheliocytes. No essential differences in the reaction of venous and aortic endothelium have been revealed in response to freezing-induced lesions. PMID- 3349183 TI - [Morphological manifestations of compensatory-adaptive processes in the liver during aging]. AB - Light and electron microscopy and morphometry revealed an age-related increase in the average size of hepatocytes and their nuclei in 24- and 30-month-old rats compared to 8-month-old animals, the density of hepatocytes distribution per area unit being decreased. In 24-month-old rats the number of binuclear hepatocytes increased with a subsequent decrease in their number in 30-month-old animals, which accounted for the shift in regeneration processes during ageing to predominantly intracellular one. The number of sinusoidal cells per area unit in three age groups was statistically similar. The results of morphometry and electron microscopy suggest that the compensatory-adaptive processes during hepatocyte ageing were mediated by intracellular regeneration, which led to cellular and nuclear hypertrophy similar to that observed in cells of static population (neurons, cardiomyocytes). PMID- 3349184 TI - Mortality and hematology associated with the ingestion of one number four lead shot in black ducks, Anas rubripes. PMID- 3349185 TI - Heat exposure and the toxicity of one number four lead shot in mallards, Anas platyrhynchos. PMID- 3349186 TI - Uptake and excretion of organochlorine pesticides by Nereis virens under normoxic and hypoxic conditions. PMID- 3349187 TI - Acute effects of mercuric chloride on intracellular GSH levels and mercury distribution in the fish Oreochromis aureus. PMID- 3349188 TI - Novel biological recycling water purification system for use in fish toxicology studies. PMID- 3349189 TI - Seasonal resistance of the shore crab, Hemigrapsus oregonesis, to saxitoxin injections. PMID- 3349191 TI - Acute toxicity of endosulfan to crabs: effect on hydromineral balance. PMID- 3349192 TI - Weight dependence of arsenic concentration in the Arabian Sea tuna fish. PMID- 3349190 TI - Toxicity of sodium chromate and 3,4-dichloroaniline to crustaceans. PMID- 3349193 TI - Trace elements in fish from the Arabian Gulf and the Shatt al-Arab River, Iraq. PMID- 3349194 TI - Organochlorine pesticide residues in fish from southern Italian rivers. PMID- 3349196 TI - Analysis of gasoline in water using a stripping preconcentration procedure. PMID- 3349195 TI - Occurrence of aflatoxins in human foodstuffs in South Africa. PMID- 3349197 TI - Effects of 2-methyl-4-chlorophenoxyacetic acid on the catalase liver activity of chicken embryos. PMID- 3349198 TI - Effect of cadmium chloride on thyroid activity of the female Indian palm squirrel, Funambulus pennanti (Wroughton). PMID- 3349199 TI - Effect of cadmium intoxication on collagen and elastin content in tissues of the rat. PMID- 3349200 TI - Metabolism and excretion of orally and intraperitoneally administered methylarsonic acid in the hamster. PMID- 3349201 TI - Effect of ethionine on hepatic mitochondrial and microsomal calcium uptake. PMID- 3349202 TI - Effects of prenatal exposure to 2,4-D/2,4,5-T mixture on postnatal changes in rat brain glutamate, GABA, protein, and nucleic acid levels. PMID- 3349203 TI - Dose response of rat liver to low level cadmium. PMID- 3349204 TI - Effect of intoxication with vanadium compounds on copper metabolism in the rat. PMID- 3349205 TI - Rapid quantification of 11 prostanoids by combined capillary column gas chromatography and negative ion chemical ionization mass spectrometry: application to prostanoids released from normal human embryonic lung fibroblasts WI38 in a culture medium. AB - The rapid and simultaneous quantification of 11 prostanoids has been carried out with a short-capillary gas chromatograph and negative ion chemical ionization (ammonia) mass spectrometer. The methoxime-trimethylsilyl ether-pentafluorobenzyl esters (MO-TMS-PFB) of nine prostanoids, PGA1, PGA2, PGB1, PGB2, PGD2, PGE1, PGE2, 6-oxo-PGF1 alpha and TXB2 and the TMS-PFB of two prostanoids, PGF1 alpha and PGF2 alpha, were separated in less than 5.5 min on a bonded OV-1 capillary column 0.25 mm i.d. x 6 m (0.15 micron thickness) using hydrogen as a carrier gas. PGD2, PGE2, PGF2 alpha, 6-oxo-PGF1 alpha and TXB2 were quantified up to 2.5 fmol injected (0.1 pmol derivatized) and both PGA2 and PGB2 up to 25 fmol injected (1 pmol derivatized). In order to maintain the stability of the prostanoids containing a carbonyl group, such as TXB2 during the purification and derivatization steps of biological materials, methyl acetate was used in place of methyl formate as an eluant for Sep-Pak C18 purification. Normal human embryonic lung fibroblasts W138 (5.63 x 10(5) cells in a log phase) produced: PGA2 15.28, PGB2 13.48, PGD2 7.95, PGE1 2.62, PGE2 177.76, PGF2 alpha 25.14, 6-oxo-PGF1 alpha 27.33 and TXB2 61.00 pmol in 10 ml of Eagle minimal essential medium. PMID- 3349206 TI - A gas chromatographic/mass spectrometric screening, confirmation, and quantification method for estrogenic compounds. AB - A method is described for the screening, quantification and confirmation of a variety of estronenic substances in animal tissues. A solid-phase extraction technique combined with a liquid/liquid extraction allows for rapid sample preparation and high throughput for the following compounds in bovine liver, muscle and kidney: diethylstilbestrol, dienestrol, hexestrol, zeranol, taleranol, zearalanone, zearalenone, zearalenol, estradiol and estriol. Gas chromatography/mass spectrometry and selected ion monitoring is used for the determination with detection limits ranging from 50 to 150 ppt. PMID- 3349207 TI - Measurement of urinary lactic, 3-hydroxybutyric, pyruvic and acetoacetic acids in a single analysis using selected ion monitoring and stable isotope labelling techniques. AB - Sodium borodeuteride treatment of urine expected to have large concentrations of pyruvic and acetoacetic acids produces lactic and 3-hydroxybutyric acids labelled with deuterium. Mass fragmentographic techniques applied to the trimethylsilyated extract of the urine spiked with more extensively labelled analogues as internal standards permit the reliable determination of lactic, pyruvic, 3-hydroxybutyric and acetoacetic acids in a single analysis. PMID- 3349208 TI - Collisional spectroscopy as a screening procedure for the determination of 2-(2 furoyl)-4(5)-(2-furanyl)-1H-imidazole from acid hydrolysis of B-poly(L-lysine) and B-albumin. AB - The direct determination of 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI), present in the acid hydrolysis products of B-poly(L-lysine) and B-albumin and which appears to be a key intermediate in the physicochemical changes occurring during the incubation of protein with glucose, has been carried out by collisional spectroscopy, using a commercial double-focusing, reverse-geometry mass spectrometer and without any sample derivatization and chromatographic separation procedures. PMID- 3349209 TI - Stereoselectivity of the 4-hydroxylation of debrisoquine in man, detected by gas chromatography/mass spectrometry. AB - A stable isotope assay for the quantification of debrisoquine (1) and its major urinary metabolite 4-hydroxydebrisoquine (2) is described. The method consists of extractive derivatization of 1 and 2 by use of 1,3-diketones, chiral derivatization of the 4-hydroxy group of 2, and gas chromatography/negative ion chemical ionization mass spectrometry in the presence of deuterated analogues of 1 and 2. In comparison with synthetic R-(-)-2 and S-(+)-2 it is shown that in vivo benzylic 4-hydroxylation of 1 is highly stereoselective, leading predominantly to S-(+)-4-hydroxydebrisoquine (enantiomeric excess greater than or equal to 90%). PMID- 3349210 TI - Quantitative determination of arsenocholine and acetylarsenocholine in aquatic organisms using pyrolysis and gas chromatography/mass spectrometry. AB - A method for qualitative and quantitative analysis of trace amounts of quaternary organoarsenicals such as arsenocholine and acetylarsenocholine has been developed. The method is based on pyrolysis, gas chromatography/mass spectrometry and use of deuterium-labelled internal standards. Arsenocholine and acetylarsenocholine have been estimated in fish from arsenic-polluted brackish water and compared with the same species of fish from unpolluted water. The investigation also includes some fish and crustacea from marine water. The presence of arsenocholine and acetylarsenocholine in different aquatic organisms indicate the existence of a general metabolic pathway for these compounds in aquatic ecosystems. PMID- 3349211 TI - Linked scan investigation of peptide degradation initiated by liquid secondary ion mass spectrometry. AB - [MH]+ ions of peptides are degraded in one step to acyl ions, indicating the presence of different [MH]+ species. In contrast to protons, cations are added mainly at the carboxylate function of a peptide zwitterion. These species are degraded by loss of the C-terminal amino acid in the form of CO and an imine. PMID- 3349213 TI - Fast atom bombardment and tandem mass spectrometry for structure determination: remote site fragmentation of steroid conjugates and bile salts. AB - A series of 35 steroid conjugates (sulfates and glucuronides) and bile salts were investigated by using fast atom bombardment and tandem mass spectrometry. Collisional activation of the [M - H]- anions of sulfate conjugates and bile salts predominantly yields fragment ions arising by reactions occurring remote from the charge site. These reactions are sometimes sensitive to differences in stereochemistry at positions remote from the charge site and are useful for positional isomer differentiation. On the other hand, collisional activation of the [M - H]- anions of the glucouronide conjugates leads primarily to charge driven fragementations. PMID- 3349212 TI - Characterization of trichothecenes by ammonia chemical ionization and tandem mass spectrometry. AB - Ammonia and deuterated ammonia chemical ionization (CI) mass spectra and collisionally activated dissociation (CAD) mass spectra of ammonium adduct ions are presented for ten trichothecenes. The samples were introduced by direct exposure probe. Effects of ion source temperature and pressure on the ammonia CI gas plasma and the formation of the ammonium adduct ion were studied. The CI conditions were optimized to produce a maximal yield for the ammonium adduct ion of trichothecenes, i.e. the parent ion for tandem mass spectral analysis. Besides source temperature and pressure, proton affinity and the stability of the ammonium adduct ion affect the relative abundance ratio of [M + H]+:[M + NH4]+ in ammonia CI and CAD mass spectra. The ratio [M + H]+:[M + NH4]+, and hence the stability of the ammonium adduct ion, are largely determined by the functional groups (hydroxy, carbonyl, acetoxy, and isovaleroyloxy) and their location in the trichothecene nucleus. The most abundant fragment ions in the ammonia CI spectra and the most abundant daughter ions in the CAD spectra of the ammonium adduct ions are formed by the losses of ammonia and functional groups as neutrals in various combinations. PMID- 3349214 TI - Step-advancement island flap for fingertip reconstruction. AB - An island flap is described for fingertip reconstruction, based on one neurovascular bundle. The design incorporates the stepladder principle, which ensures the provision of ample skin with full tactile sensibility in the required position, without the risk of longitudinal volar scarring and with good nail support when necessary. Fourteen such repairs have been carried out with satisfactory results and no complications. PMID- 3349215 TI - The treatment of tattoos with trichloracetic acid: experience with 670 patients. AB - A review of out-patient treatment of tattoos with trichloracetic acid has been undertaken. Six hundred and seventy patients have been treated during the 6-year period between 1979 and 1984. The simple and inexpensive technique is described and the results presented. PMID- 3349216 TI - Versatility of temporal muscle and fascial flaps. AB - The muscle and superficial fascia of the temporal area differ in their physical characteristics, vascular supply and clinical applications. Both can be employed independently or simultaneously as regional flaps in the reconstruction of a variety of complex craniofacial defects. The present paper reviews the anatomy, surgical technique and utilisation of temporal flaps. PMID- 3349217 TI - Reconstruction of mandibular defects with metallic prostheses and microvascular jejunal autografts: an experimental study. AB - A study was undertaken to determine the adequacy of vascularised jejunum to provide stable mucosal cover over a non-biological mandibular substitute. Employing a canine model, composite intra-oral bone-mucosal defects were created and reconstructed with a metal plate covered by a microvascular jejunal patch. These were followed for six months and were assessed clinically, histologically and radiologically. Rapid mucosal healing occurred in all cases. The autografts conformed to the contour of the prosthesis and adequate tongue mobility was preserved. All mandibles remained stable throughout the follow-up period. Histologically, short villi covered the jejunal grafts to three months whilst at six months both normal and abnormal jejunal mucosal morphology was evident. PMID- 3349218 TI - Fasciocutaneous flaps for burn reconstruction: a report of 57 flaps. AB - We have used 57 fasciocutaneous flaps in 24 patients to correct burn contractures. There were six complications, four of which healed with dressings alone. The flaps were used either locally (22 patients) or as a cross-leg flap (2 patients). The local flaps have clearly shown that grafted areas can be raised as flaps provided that the fascia is included in the flap, and that the flap can also be based distally. Fasciocutaneous flaps have several advantages over the technique of cross-cutting the contracture, followed by split skin grafting. Firstly, there is no skin graft, which may result in further contracture. Secondly, if a patient does not have a skin graft on the secondary defect (83% in this series), the patient has the advantage of a shorter hospital stay. The techniques of the design and raising of fasciocutaneous flaps for burn reconstruction are discussed. PMID- 3349219 TI - Tissue expansion and flaps for surgical correction of male pattern baldness. AB - The author describes how to use a long, non-delayed temporo-parieto-occipital (TPO) flap across the total frontal hairline, and tissue expansion for coverage of the bald area behind the flap. This concept can be used successfully in extensively bald patients where two TPO flaps would not be sufficient to cover the total bald area. An even growth of hair is achieved. When the hair "reserve" is good, quite dense hair can be reconstructed. The flap described is performed under local anaesthesia without delays and does not have the risk of postauricular necrosis sometimes seen with certain designs of TPO flaps. PMID- 3349220 TI - Phalloplasty using the free radial forearm flap. AB - Our experience of phalloplasty using the radial forearm flap in five transsexual cases is reported. The results are disappointing due to the high incidence of complications. We had partial success in two cases, both complicated by a fistula, and complete failure in three cases due to vascular thrombosis. PMID- 3349221 TI - The subaxillary pedicled flap. AB - The subaxillary fasciocutaneous flap is a new pedicled flap designed and developed by us for resurfacing defects on the dorsum of the hand, thumb, fingers and web-spaces. The lack of mobility and inability of the patient to dress properly during transfer of a groin or hypogastric flap prompted us to develop this flap which is based on the direct cutaneous branch of the subscapular thoracodorsal arterial axis to the lateral thoracic region. It consists of skin, subcutaneous tissue and the underlying fascia. It is located in the region of the lower half of the lateral chest wall extending from 5th to 10th rib to the mid axillary line and can be raised without any delay. The donor defect can be closed primarily or skin grafted if necessary and can be very easily taken care of during hospitalisation. It can be nicely concealed later on in life. The subaxillary fasciocutaneous flap has been tried by us in 10 cases and the results are presented in this paper. PMID- 3349222 TI - Reconstruction of the middle-aged torn earlobe: a new method. AB - This paper describes a new method of reconstructing acquired complete and incomplete cleft earlobes which are elongated and have lost their normal bulk due to the wearing of heavy, dangling earrings. Results have been good and problems of breakdown of the repair have not been reported over a period of 2 years. PMID- 3349223 TI - An inducement to exercise after flexor tendon repair. AB - A simple gadget is described which provides the encouragement necessary for children to exercise in dynamic traction following flexor tendon repair in the hand. Its use has made possible the incorporation of dynamic splinting into the aftercare of very young patients. PMID- 3349224 TI - Artificial double vagina in association with Rokitansky syndrome. AB - A case of Rokitansky syndrome is described where the typical anomalies of the entity were associated with cribriform hymen. The appearance of the external genitalia led to an erroneous diagnosis of complete vaginal agenesis and to surgical creation of an artificial vagina by the McIndoe technique at the patient's age of 19. She had a satisfactory sexual life subsequently. Ten years following the surgery, routine examination revealed that the patient had an essentially normal vagina with a blind upper ending. Prior to this, she and her husband had been unaware of the fact that their marital relations were conducted through her natural vagina during the years of their sexual activities. PMID- 3349225 TI - Squamous cell carcinoma presenting as a painful scar following a single injury. AB - We report a case of squamous cell carcinoma of the skin presenting as a painful scar, following a single injury. There was no ulceration of the overlying tissues. The possible pathogenesis, with reference to mechanical and chemical trauma, is discussed. PMID- 3349226 TI - Voltage-independent catecholamine release mediated by the activation of muscarinic receptors in guinea-pig adrenal glands. AB - 1. The differences between the mechanisms of muscarinic and nicotinic receptor mediated catecholamine secretion with respect to their dependence on voltage changes and extracellular Ca were examined using perfused adrenal glands of the guinea-pig. 2. Acetylcholine (ACh, 10(-6) to 10(-3) M) caused a dose-dependent increase in catecholamine secretion. The ED50 value for ACh was 7 x 10(-5) M. In the presence of atropine (10(-5) M), the dose-response curve for ACh was shifted to the right. Hexamethonium (5 x 10(-4) M) preferentially reduced the responses to higher concentrations of ACh (greater than 10(-5) M). Pilocarpine (5 x 10(-4) M) and nicotine (3 x 10(-5) M) also stimulated catecholamine release. 3. During perfusion with isotonic KCl solution, ACh and pilocarpine, but not nicotine, evoked catecholamine secretion. These responses were abolished by atropine (10( 6) M). Pilocarpine-stimulated catecholamine secretion was enhanced during perfusion with isotonic KCl solution. Under these conditions, hexamethonium (10( 3) M) significantly augmented ACh-evoked catecholamine release. 4. During perfusion with either Ca-free isotonic KCl or Ca-free Locke solution, ACh and pilocarpine caused a partial increase in catecholamine secretion whereas nicotine and high K solution (56 mM) did not. The responses to ACh and pilocarpine were completely inhibited by atropine but not by hexamethonium. 5. When guinea-pig adrenal glands were perfused with isotonic KCl solution containing 2.2 mM Ca which was subsequently removed and replaced with EGTA, ACh-induced catecholamine secretion was similar in magnitude to that observed during perfusion with Locke solution. 6. We conclude that both nicotinic and muscarinic receptors are involved in ACh-induced catecholamine secretion from guinea-pig adrenal chromaffin cells. Activation of muscarinic or nicotinic receptors appears to stimulate catecholamine release through different mechanisms with respect to both voltage-dependence and Ca requirements. PMID- 3349227 TI - A comparison of fast and slow depolarizations evoked by 5-HT in guinea-pig coeliac ganglion cells in vitro. AB - 1. 5-Hydroxytryptamine (5-HT) was applied by pressure ejection to coeliac ganglion cells of the guinea-pig maintained in vitro and responses measured intracellularly. 2. Cells responded in one of three ways to 5-HT: by (a) a fast, transient depolarization (43%), (b) a fast transient followed by a slow depolarization (biphasic response, 30%) or (c) a slow sustained depolarization (25%). 3. Fast depolarizations (response (a) above] were graded according to the duration of the ejection pulse. Maximal responses had a mean amplitude of 12 +/- 0.8 mV, a duration of 6.4 +/- 1.0 s, a latency of 0.4 +/- 0.1 s, were associated with a fall in membrane input resistance, increased in amplitude by hyperpolarization and probably mediated by an increased conductance to Na and K. The estimated reversal potential was -22.8 +/- 2.4 mV (n = 14). The maximal fast response seen in biphasically-responding cells (b) appeared similar to fast response (a). 4. Fast depolarizations (a) showed marked tachyphylaxis and were abolished by superfusion of the ganglion with 5-HT (100 microM). They were reduced in amplitude by tubocurarine (10-100 microM, pIC50 4.4), MDL 72222 (1-5 microM, pIC50 5.8), quipazine (1 microM reduced responses by 65 +/- 15%, n = 3), ICS 205-930 (1 microM reduced responses by 64 +/- 14%, n = 7) and metoclopramide (10 microM reduced responses by about 45%), but were unafected by methysergide (up to 1 microM) or hexamethonium (up to 1 mM). 5. Slow depolarizations (c) varied in amplitude with the duration of the ejection pulse. Maximal responses had a mean amplitude of 6.4 +/- 0.7 mV, a duration of 62 +/- 6 s, a latency of 3.5 +/- 0.8 s and were reduced in amplitude by methysergide (0.1-1 microM, pIC50 6.5) but not by MDL 72222 (1 microM). The maximal slow component in biphasically responding cells (b) was similar in amplitude and duration to slow response (c), was partially blocked by methysergide (1-5 microM) in 4 of 6 cells and was enhanced by tubocurarine (50 microM) which reduced the fast component. 6. Slow depolarizations (b,c) were associated with either a small reduction or no change in membrane input resistance depending on the cell studied. Hyperpolarization had variable effects on slow depolarization amplitude. 7. It was concluded that the fast, phasic depolarization is mediated by an ionic mechanism and by receptors both of which are distinct from those involved in the slow depolarization. The receptor mediating the fast depolarization is a 5-HT3 receptor while that mediating the slow depolarization has yet to be identified. PMID- 3349228 TI - Cardiovascular effects of apamin and BRL 34915 in rats and rabbits. AB - 1. The cardiovascular effects of apamin, a selective blocker of certain calcium activated potassium channels, and BRL 34915, a vasodilator thought to act by opening of potassium channels, have been investigated in vivo in rats and rabbits. 2. In anaesthetized normotensive rats, apamin (0.05 and 0.15 mg kg-1, i.v.) potentiated angiotensin II pressor responses but did not modify baseline blood pressure or heart rate. 3. Apamin (0.15 mg kg-1, i.v.) was without cardiovascular effects in rabbits. 4. BRL 34915 (0.1 and 0.3 mg kg-1, i.v.) lowered blood pressure in rats dose-dependently and caused reflex tachycardia. The heart rate increase was abolished by prior administration of the beta adrenoceptor blocker bopindolol (0.1 mg kg-1, i.v.). 5. In anaesthetized rabbits, regional blood flow measurements (with radioactive tracer microspheres) showed that BRL 34915 (3 to 30 micrograms kg-1, i.v.) caused marked vasodilatation in the stomach, with increases in flow also to the heart and small intestine. Brain blood flow also tended to increase. Blood flow to the kidneys was reduced by BRL 34915, whereas flow to skeletal muscle was unchanged. 6. Apamin pretreatment did not modify the blood pressure lowering activity of BRL 34915 in rats. The site at which BRL 34915 acts to cause vasodilatation in vivo thus appears to be apamin insensitive. PMID- 3349229 TI - Interactions of the imidazodiazepine Ro 15-4513 with chemical convulsants. AB - 1. The proconvulsant effects of the imidazodiazepine Ro 15-4513, were investigated in mice by use of intravenous infusion of a variety of convulsant drugs. 2. Dose-response and time course studies of Ro 15-4513 against gamma aminobutyric acid (GABA) antagonists were performed. On the basis of these studies a maximally effective dose of 5 mg kg-1 was administered 5 min before the determination of seizure thresholds in subsequent experiments. 3. Ro 15-4513 (5 mg kg-1) significantly lowered seizure thresholds to pentylenetetrazole, bicuculline and the convulsant benzodiazepine Ro 5-3663, but failed to alter seizure thresholds to picrotoxin, strychnine, caffeine and quipazine. 4. Ro 15 4513 significantly raised seizure threshold to the benzodiazepine receptor inverse agonist methyl 6,7-dimethoxy-4 ethyl-beta-carboline-3-carboxylate (DMCM). 5. These results are discussed in relation to other studies investigating the proconvulsant and alcohol-antagonizing effects of Ro 15-4513. PMID- 3349230 TI - Gastric mucosal damage induced by local intra-arterial administration of Paf in the rat. AB - 1. A technique for the close-arterial administration of substances to the rat stomach in vivo has been developed. 2. Intra-arterial infusion of platelet activating factor (Paf, 10-50 ng kg-1 min-1 for 10 min) induced macroscopically assessed damage in the corpus mucosa, characterized as vasocongestion and necrosis. 3. The threshold intra-arterial doses of Paf that induced histologically assessed damage in the antrum and corpus of the stomach (10 and 5 ng kg-1 min-1, respectively) produced minimal systemic hypotension (less than 20 mmHg) suggesting a dissociation between these events. 4. Pretreatment with the Paf-antagonist, L-652,731 (2.5 mg kg-1 i.v.) prevented the gastric damage induced by local infusion of Paf. 5. Intravenous infusion of Paf (25 ng kg-1 min-1) did not significantly damage the gastric mucosa, in contrast to the same dose infused locally, yet Paf administered by either route produced a comparable degree of hypotension. Such findings suggest minimal metabolism of Paf during its passage through the gastric circulation. 6. Local intra-arterial infusion of Paf in doses as low as 0.25 ng kg-1 min-1, which had no systemic hypotensive actions, significantly induced gastric damage in the presence of intragastric 20% ethanol. 7. These observations support a local role for Paf in the pathogenesis of gastric irritation and ulceration, such as that observed during endotoxin shock or bacterial infection. The present technique is thus useful for the study of locally administered substances on gastric function and integrity. PMID- 3349231 TI - A comparison between atria from control and streptozotocin-diabetic rats: the effects of dietary myoinositol. AB - 1. Atria, isolated from control rats, six-week streptozotocin-diabetic rats and from similarly diabetic rats treated with myo-inositol (MI) were compared. The MI treatment was shown to reverse the depressed sciatic nerve MI which was observed in the untreated diabetic group. 2. Spontaneously beating atria from the untreated diabetic animals beat more slowly, and with greater force than tissues from the control group. When electrically driven at 4 Hz they were found to be less sensitive to the negative inotropic effect of acetylcholine. No differences between the two groups were observed in responses to isoprenaline. 3. Intramural nerve stimulation in the presence of 10(-6)M propranolol (vagal stimulation) had a greater negative inotropic effect in the untreated diabetic rat atria than in the controls. Positive inotropic responses to nerve stimulation in the presence of 10(-6) M atropine (sympathetic stimulation) were not significantly different between the two groups. 4. Atria from the MI-treated diabetic animals were found to have a lower spontaneous contractile force and greater sensitivity to acetylcholine than tissues from the untreated diabetic animals. The values obtained in both cases were similar to those from the controls. No significant effect of MI treatment on spontaneous contractile rate or on responses to nerve stimulation was demonstrated. 5. Atrial (mainly myocardial) MI was measured in additional control, six-week diabetic and six-week MI-treated diabetic animals. A significantly higher concentration was observed in the MI supplemented group compared to the untreated diabetic group. The mean MI content in the latter group was lower than that obtained from control tissues but not significantly so. 6. The results implicate MI depletion either in the neurones or in the myocardium in at least some of the changes observed. Possible mechanisms involved are discussed. PMID- 3349232 TI - Clonidine and morphine increase [3H]-noradrenaline overflow in mouse vas deferens. AB - 1. Field stimulation of mouse isolated vas deferens produced a biphasic contraction that consisted of an initial brief non-adrenergic, non-cholinergic (NANC) twitch, followed by a more prolonged noradrenergic component. 2. Field stimulation of vasa, previously loaded with [3H]-noradrenaline ([3H]-NA), increased the amount of radioactivity in the Krebs bathing solution; 77% of this radioactivity was derived from [3H]-NA. 3. Tetrodotoxin (3 x 10(-6) M) abolished the biphasic motor response to field stimulation and the accompanying increased overflow of [3H]-NA. 4. Morphine (10(-7)-10(-5) M) inhibited the initial NANC component but potentiated the secondary noradrenergic component of the motor response to field stimulation. Morphine also increased the field stimulation induced overflow of radioactivity. Naloxone (10(-6) M) antagonized the effects of morphine on the motor response and also on the overflow of radioactivity. 5. Clonidine (10(-9)-10(-7) M) inhibited the initial NANC component but potentiated the secondary noradrenergic component of the motor response to field stimulation. Clonidine also increased the field stimulation-induced overflow of radioactivity. 6. The ability of morphine (10(-7) M) and of clonidine (10(-9) M) to potentiate the field stimulation-induced overflow of radioactivity persisted in the presence of a combination of tranylcypromine (10(-5) M), desmethylimipramine (10(-5) M) and 17-beta-oestradiol (10(-5) M). 7. The inhibition of the initial NANC component of the motor response to field stimulation produced by morphine and clonidine may be related to the ability of these drugs to potentiate both the secondary noradrenergic component and the overflow of radioactivity, if the NANC transmitter is involved in regulating NA release. PMID- 3349233 TI - Actions of vanadate on vascular tension and sodium pump activity in cat isolated cerebral and femoral arteries. AB - 1. The mechanisms involved in the responses induced by sodium vanadate (Va3 VO4) on cat cerebral and femoral arteries were studied. The possibility that these responses were due to Na+, K+-ATPase inhibition was investigated by measuring the effect of vanadate on [3H]-ouabain binding to arterial membrane fractions, K+ induced vasodilatation and ouabain-sensitive 86Rb+ uptake. 2. The vanadium compounds (Na3VO4, VOSO4, VCl3 and O5V3) induced similar, concentration-dependent contractions in each kind of artery, the cerebral vessels being the most sensitive to these compounds. 3. Exposure of the arteries to a low-Na+ (25 mM) solution suppressed the contraction caused by vanadate in femoral but not in cerebral arteries. 4. Vanadate-induced contractions were reduced in Ca2+-free medium but remained unaffected by 3 x 10(-6) M phentolamine, reserpine pretreatment or 3 x 10(-6) M verapamil in both kinds of artery. 5. The addition of 7.5 mM K+ to the arteries immersed in a K+-free solution induced vasodilatation, which was not modified by 10(-3) M vanadate. 6. The consecutive administration of ouabain (10(-4) M) and vanadate (10(-3) M) (or vice versa), or the simultaneous administration of both agents (10(-8) to 10(-3) M) appeared to produce an additive contraction in both types of artery. 7. Vanadate (10(-7) to 10(-3) M) did not displace the [3H]-ouabain binding to arterial membrane fractions of these arteries, whereas 10(-4) M ouabain did. 8. In both kinds of artery, total 86Rb+ uptake was reduced by ouabain (10(-8) to 10(-3) M), in a concentration-dependent manner, whereas it was not modified by vanadate (10(-8) 10(-3) M). 9. These results suggest that vanadate induces contraction in both types of artery by a mechanism unrelated to Na+, K+-ATPase inhibition. Such a mechanism is likely to be related to inhibition of the Ca2-ATPase of the cell membrane and/or the sarcoplasmic reticulum. PMID- 3349234 TI - The cholecystokinin receptor antagonist L364,718 increases food intake in the rat by attenuation of the action of endogenous cholecystokinin. AB - 1. To determine the role of endogenous cholecystokinin (CCK) in the regulation of food intake, the effects of the potent CCK receptor antagonist L364,718 were investigated on the intake of a palatable diet in non-deprived rats. The effect of a single dose of proglumide was also investigated for comparative purposes. In addition, the ability of L364,718 to antagonize the reduction in food intake produced by exogenous cholecystokinin-octapeptide (CCK8) or bombesin in food deprived rats was determined. 2. L364,718 (10-100 micrograms kg-1, i.p.) increased the intake of palatable diet during the 30 min test period. Proglumide (300 mg kg-1, i.p.) also increased the intake of palatable diet. Conversely, CCK8 (0.5-5 micrograms kg-1, i.p.) produced a reduction in the intake of the diet. 3. In fasted rats, L364,718 (100 micrograms kg-1, i.p.) antagonized the reduction in food intake produced by CCK8 (10 micrograms kg-1, i.p.) but not that produced by bombesin (50 micrograms kg-1, i.p.). L364,718 did not increase food intake in these animals when measured over a 6 h period. 4. It is concluded that L364,718 is a potent, selective antagonist of the effects of CCK8 on food intake. The observation that L364,718 and proglumide increase the intake of a palatable diet provides some evidence that endogenous CCK is involved in the control of food intake in this model. PMID- 3349235 TI - Antinociceptive effects of the novel opioid peptide BW443C compared with classical opiates; peripheral versus central actions. AB - 1. To investigate peripherally mediated antinociceptive effects of opioids, the activity of a novel polar enkephalin analogue H-Tyr-D-Arg-Gly-Phe (4-NO2)-Pro-NH2 (BW443C) has been compared with those of classical tertiary opiates against different nociceptive stimuli in the mouse. 2. In chemically-induced writhing models BW443C, administered subcutaneously, demonstrated dose-related antinociceptive effects less potent than morphine and of a similar order to pethidine and D-propoxyphene. In assays using heat as the noxious stimulus BW443C was markedly less potent than any of the opiates tested. 3. In heat-induced assays, but not in chemically-induced writhing assays, BW443C demonstrated a 'U' shaped dose-time response relationship. Morphine, pethidine and D-propoxyphene showed simple, approximately linear, dose-time effects in all assays. 4. When given subcutaneously, the inhibitory effects of BW443C and morphine in chemically induced writhing were antagonized by naloxone given intraperitoneally. The inhibitory effects on writhing of BW443C, but not those of morphine, were also antagonized by prior intraperitoneal administration of the quaternary opioid antagonist N-methyl nalorphine. When this antagonist was administered intracerebroventricularly, the antinociceptive effects in writhing of both BW443C and morphine were antagonized. 5. It is concluded that BW443C, being only poorly able to cross the blood brain barrier, demonstrates peripherally mediated opioid antinociceptive effects in chemically-induced writhing models. In heat-induced models, that detect centrally acting opioids, BW443C is effective only at high doses and at time intervals after dosing sufficient to allow slow penetration of drug into the CNS. It is suggested that the peripheral antinociceptive actions of BW443C are mediated by inhibition of sensory neurones. PMID- 3349236 TI - Effects of codeine, morphine and a novel opioid pentapeptide BW443C, on cough, nociception and ventilation in the unanaesthetized guinea-pig. AB - 1. Antitussive, antinociceptive and respiratory depressant effects of codeine, morphine and H.Tyr.D-Arg.Gly.Phe(4-NO2) Pro.NH2 (compound BW443C) were investigated in unanaesthetized guinea-pigs. Antagonism of the antitussive and antinociceptive effects was investigated by the use of nalorphine and N methylnalorphine. Naloxone was used to antagonize respiratory depression. 2. Antitussive ED50s (with 95% confidence limits) for inhibition of cough induced by citric acid vapour were for codeine, morphine and BW443C respectively, 9.1(5.8 15), 1.3(0.7-2.4) and 1.2(0.6-2.6) mg kg-1 s.c. and 8.7(4.2-12), 1.6(1.2-1.9) and 0.67(0.002-3.3) mg kg-1, i.v. The antitussive effects of subcutaneous codeine (25 mg kg-1) morphine (8.1 mg kg-1) and BW443C (2.5 mg kg-1) were significantly antagonized by subcutaneous nalorphine (3.0 mg kg-1) and N-methylnalorphine (3.0 mg kg-1). 3. In the multiple toe-pinch test, the antinociceptive ED50s (with 95% confidence limits) of codeine and morphine were 18(16-22) and 2.3(0.4-4.3) mg kg 1, s.c., respectively. Compound BW443C was ineffective in doses of 2.5 and 10 mg kg-1 s.c., a result consistent with its lacking penetration into the CNS. Subcutaneous nalorphine (3.0 mg kg-1) antagonized the antinociceptive action of codeine (25 mg kg-1) and morphine (8.1 mg kg-1). In contrast, N-methylnalorphine (3.0 mg kg-1) had no significant effect on the antinociceptive action of codeine and morphine, suggesting lack of penetration of the CNS by N-methylnalorphine. 4. At doses near to the i.v. ED50 values for the antitussive activity, morphine (1.5mg kg- ', i.v.) and codeine (10mg kg-', i.v.) caused small but significant depressions of ventilation (7.0 +/- 2.3% and 16.5 +/- 8.4% respectively). Higher doses of morphine (10, 30 and 60mg kg- ', i.v.) caused further doserelated depression of ventilation (9.6 +/- 5.3%, 22.4 +/- 6.2% and 36.2 +/- 9.6% respectively) whereas codeine (30 and 60mg kg-' i.v.) caused stimulation of ventilation which was marked (191.3 +/- 43.9%) at 60 mg kg-'. 5. Compound BW443C in doses of 1 or 10mgkg-',i.v. (approximately equal to, and 10 times the EDo for antitussive activity) did not cause significant depression of ventilation. Only at higher doses of 30 and 60mg kg-', i.v. was there a significant decrease in minute volume (13.1 +/- 6.8% and 15.9 +/- 1.89% respectively). The depression of ventilation caused by either BW443C (60mg kg-', i.v.) or morphine (60mg kg-', i.v.) was prevented by pretreatment with naloxone (3mg kg-', i.v.) administered 15 min before morphine or BW443C. 6. These results in the guinea-pig support the hypothesis that the antitussive action of the opiates codeine and morphine and the opioid pentapeptide BW443C do not require penetration of these drugs into the CNS. PMID- 3349238 TI - Proximal, distal and total stomach emptying of a digestible solid meal in normal subjects. AB - The gastric fundus and antrum probably play different roles in the emptying of solids and liquids in man, but there is little information about the intragastric distribution of food. We have used a new radionuclide technique to quantify proximal, distal and total stomach emptying of a digestible solid meal (100 g of 99Tcm-labelled liver/ground beef given with 150 ml of 10% dextrose) in 13 normal subjects. A proximal reservoir area was seen after consumption of the meal, and used to define the proximal stomach region. A line drawn immediately below this area divided the total stomach region into proximal and distal stomach. Emptying from the total stomach exhibited two phases--an initial lag period (median 41 min, range 21-57 min), followed by approximately linear emptying. Redistribution of food from the proximal to the distal stomach was a major component of the lag period in 11 of the 13 subjects. In the remaining two subjects, redistribution was rapid (proximal 50% emptying time of 4 and 10 min) and antral retention was the major component of the lag period. In seven subjects, a region of reduced activity (contraction band) was seen. The midpoint of this band closely approximated to the line used to divide proximal and distal stomach. We suggest that a contraction band may be responsible for the proximal gastric reservoir seen after meal consumption and plays an important role in the redistribution and emptying of digestible solid food from the stomach. There is considerable variation between normal subjects in the rate of transfer of digestible solid food from the proximal to the distal stomach. PMID- 3349239 TI - In-vivo measurement of spin lattice relaxation time (T1) of bone marrow in healthy volunteers: the effects of age and sex. AB - Magnetic resonance images of the spine, sternum, femoral heads and upper femoral shafts were obtained from 90 healthy volunteers to determine the normal ranges of spin lattice relaxation time (T1) for different regions of the bone marrow. The influence of age, sex and oral contraceptive usage on bone marrow T1 was assessed. Differences observed between the T1 of the various regions of the bone marrow examined were consistent with the expected distribution of erythropoietic cells and fatty marrow. Bone marrow T1 was found to decrease with age, significantly lower mean T1 values being observed in subjects over 40 years of age than for those in the 20-40 years age group. The mean bone marrow T1 of females in the 20-40 years age group was significantly higher than that for males of comparable age. For subjects over 40 years of age, the difference in bone marrow T1 observed between males and females was not significant. Oral contraceptive usage had no effect on bone marrow T1. PMID- 3349240 TI - In-vivo measurement of spin lattice relaxation time (T1) of liver in healthy volunteers: the effects of age, sex and oral contraceptive usage. AB - Magnetic resonance imaging of 81 healthy adult volunteers has been undertaken to establish the normal range of liver spin lattice relaxation time (T1) at 0.08 tesla. The influence of age, sex and oral contraceptive usage has been assessed. Liver T1 decreased with age. The mean liver T1 of subjects under 40 years of age was significantly longer than that of older subjects. A wider range of T1 values was observed in the younger age group. No difference in T1 was found between males and females who were not oral contraceptive users. The mean liver T1 of females who were taking the pill was significantly longer than that of females of similar age who were not oral contraceptive users. Serial examinations of eight oral contraceptive users showed that mean liver T1 values were significantly longer in the 3 weeks during which they were taking the pill than during the week off the pill. PMID- 3349241 TI - Costing imaging procedures. AB - The existing National Health Service financial system makes comprehensive costing of any service very difficult. A method of costing using modern commercial methods has been devised, classifying costs into variable, semi-variable and fixed and using the principle of overhead absorption for expenditure not readily allocated to individual procedures. It proved possible to establish a cost spectrum over the financial year 1984-85. The cheapest examinations were plain radiographs outside normal working hours, followed by plain radiographs, ultrasound, special procedures, fluoroscopy, nuclear medicine, angiography and angiographic interventional procedures in normal working hours. This differs from some published figures, particularly those in the Korner report. There was some overlap between fluoroscopic interventional and the cheaper nuclear medicine procedures, and between some of the more expensive nuclear medicine procedures and the cheaper angiographic ones. Only angiographic and the few more expensive nuclear medicine procedures exceed the cost of the inpatient day. The total cost of the imaging service to the district was about 4% of total hospital expenditure. It is shown that where more procedures are undertaken, the semi variable and fixed (including capital) elements of the cost decrease (and vice versa) so that careful study is required to assess the value of proposed economies. The method is initially time-consuming and requires a computer system with 512 Kb of memory, but once the basic costing system is established in a department, detailed financial monitoring should become practicable. The necessity for a standard comprehensive costing procedure of this nature, based on sound cost accounting principles, appears inescapable, particularly in view of its potential application to management budgeting. PMID- 3349237 TI - Proceedings of the British Pharmacological Society. 6th-8th January, 1988. Abstracts. PMID- 3349242 TI - Extending the range of sensitivity for detecting DNA strand breaks. PMID- 3349244 TI - Entrapment of renal calculi by Malecot nephrostomy tubes. PMID- 3349243 TI - The use of magnetic resonance imaging in the planning of iodine 125 therapy for melanoma of the choroid. PMID- 3349245 TI - Computed tomography findings in disseminated paragonimiasis. PMID- 3349246 TI - A simple graphical method for deriving kinetics of repair from fractionated and protracted irradiations. PMID- 3349247 TI - Parasymphyseal and associated insufficiency fractures of the pelvis and sacrum. AB - Eleven post-menopausal women presenting with a parasymphyseal insufficiency fracture of the pubis are reported. The plain radiographs showed delayed healing with a mixed lytic and sclerotic area developed at the fracture site simulating a malignant lesion. Aetiological factors included post-menopausal osteoporosis, rheumatoid arthritis and steroid therapy, previous hip replacement and pelvic radiotherapy. Ten patients had concomitant fractures of the pelvis, including nine with sacral fractures. These were all initially missed on presentation because of the subtle radiographic signs of a longitudinal band of sclerosis, usually bilaterally, in the sacral ala. Bone scanning was shown to be the most sensitive technique in detecting the sacral fractures by demonstrating increased uptake in the sacral ala as well as the other fractures of the pelvis. Computed tomography in three cases was helpful in confirming the presence of fractures and excluding the possibility of malignancy. PMID- 3349248 TI - The appearance of the inferior thyroid veins on computed tomography. AB - Computed tomography (CT) scans of the mediastinum in 80 patients were reviewed retrospectively to determine the nature of small opacities which are identified on contiguous cuts. These structures varied in number from one to five. The pattern of enhancement, appearance on contiguous CT sections and position in the mediastinum led us to believe that these represent inferior thyroid veins. To our knowledge their appearance on CT has not been reported previously. PMID- 3349249 TI - Flow cytometric evaluation of the effects of 2.3 MeV neutrons and 240 kV X rays on mouse spermatogenic S-phase cells using bromodeoxyuridine incorporation. AB - A sensitive flow cytometric assay has been developed to assess the effect of X rays or neutrons on the DNA-synthesizing ability of mouse testis cells. The dose to reduce the labelling index (LI) to 50% (ED50) was 25 cGy for X rays and 5 cGy for neutrons, giving a relative biological effectiveness (RBE) of 5.0. A significant reduction of the LI was seen at X-ray doses as low as 10 cGy. Neutron treatment resulted in an exponential decrease in functional S-phase cells while the X-ray response was biphasic. The sensitivity and rapidity of the assay would be suitable for use in biological dosimetry. PMID- 3349250 TI - Treatment of choroid metastases. AB - Sixteen patients with choroid secondary tumours were treated with irradiation consisting of 40-50 Gy in 3-5 weeks. There were 14 female patients with breast cancer, one male patient with prostatic cancer and one male patient with cancer of unknown origin. In four cases bilateral ocular metastases were seen. Ten out of 20 treated eyes showed complete response to treatment, seven out of 20 showed partial response and three out of 20 were not influenced by irradiation. Survival of patients, all having widespread metastatic disease, was 3-48 months (median 20 months). All patients responding to treatment showed increased quality of life. PMID- 3349251 TI - A comparison of diagnostic radiology practice and patient exposure in Britain, France and Italy. AB - Surveys have been conducted in Britain, France and Italy, using essentially the same techniques, to establish the level of provision of diagnostic radiology services, the frequency of X-ray examinations and examples of the radiation doses delivered to patients in each country. Different national strategies for conducting some types of X-ray examination and marked differences in the general availability of this aspect of health care indicate that the justification and optimization of medical exposures is not interpreted in the same way in these countries. PMID- 3349252 TI - Evidence on computed tomography of pseudotumour cerebri in hypoparathyroidism. PMID- 3349253 TI - Computed tomography in pulmonary papillomatosis. PMID- 3349254 TI - Monitoring of bladder neoplasia by low-field magnetic resonance imaging. PMID- 3349255 TI - Biological dosimetry at the tissue-barium sulphate interface: a jejunal crypt survival assay. PMID- 3349256 TI - Cancer: the failure of treatment. PMID- 3349257 TI - Safety of gamma camera flood sources. PMID- 3349258 TI - Out-of-hours radiology. PMID- 3349259 TI - Magnetic resonance imaging of benign ovarian masses. AB - Forty-one patients with 45 pelvic mass lesions were assessed by magnetic resonance imaging (MRI). All lesions were initially considered to be benign ovarian masses with this diagnosis confirmed in 36 lesions. The characteristics on MRI are analysed and features useful in predicting histological type identified. Our results indicate that a high, though not absolute, level of diagnostic specificity should be obtainable in identification of ovarian pathology. PMID- 3349260 TI - The management of intussusception. AB - A scheme of management to achieve maximum success in hydrostatic reduction of intussusception is presented. This takes into account patient selection, radiological technique and the follow-up clinical assessment. By standardizing the management we have increased our success rate and avoided laparotomy in 64% of our patients. Most of the patients in whom the technique failed had infarcted bowel which required resection. PMID- 3349261 TI - Changes in the cell kinetics of pig epidermis after single doses of X rays. AB - Changes in the cell kinetics of pig epidermis have been investigated after irradiation with single doses of 15 Gy and 20 Gy of X rays. The epidermis exhibited an initial degenerative phase when the rate of cell depletion was independent of radiation dose. Changes consistent with repopulation were evident between the 14th and 18th day after irradiation. The severity of cell depletion and the rate of recovery of the epidermis were dose dependent. The regenerative phase was characterized by an increased cell proliferation; values for the labelling index (LI) were greater than those in the non-irradiated epidermis, from 14 days after 15 Gy and from 18 days after 20 Gy. The LI was still elevated at the end of the observation period, i.e. Day 56. No change in the time for DNA synthesis was found. Eighteen days after 15 Gy and 22 days after 20 Gy, islands of cells (colonies), with an appearance similar to the cells in the normal epidermis, were seen. The minimum turnover time (TT) for the proliferating cells of the basal layer of the epidermis in radiation-damaged skin was 61-68 h as compared with 125 h in unirradiated skin. For the basal cells in the colonies, TT was 16-22 h. PMID- 3349262 TI - Radiation-induced outgrowth inhibition in explant cultures from surgical specimens of five human organs. AB - An explant outgrowth technique to determine the radiation response of five different human organs (bladder, oesophagus, colon, breast and thyroid) is described. In each case except thyroid, where malignancies are rare, data are presented for normal and malignant tissue. Results show that variations in response, consistent with those observed in vivo, can be measured. Tumours were in all cases highly resistant to radiation relative to their corresponding normal tissue. Possible reasons for this are discussed. The method may prove useful in the prediction of the radiobiological response for tumour and surrounding normal tissue where post-operative therapy is planned. PMID- 3349263 TI - Induction of sister-chromatid exchanges by d(42 MeV)-Be neutrons in unstimulated human-blood lymphocytes. AB - The ability of d(42 Mev)-Be neutrons and 250 kV X rays to produce sister chromatid exchanges (SCE) has been re-examined using unstimulated (G0) human blood lymphocytes. Contrary to a previous report, the neutrons produced a significant and dose-dependent increase in SCE. X rays, as previously, produced no measurable increase at any absorbed dose. The relative biological effectiveness (RBE) for this end-point is therefore undefined and effectively infinite. In contrast to the findings of many workers, the between-cell distributions of SCE were, in most cases, underdispersed. This could imply that the SCE burden of a cell was not selectively neutral in these experiments. PMID- 3349264 TI - Dynamic monitoring of output on a superficial X-ray set using a solid-state device. PMID- 3349265 TI - Use of a personal computer to measure gamma camera spatial resolution. PMID- 3349266 TI - The potential of cylindrical co-ordinate three-dimensional surface models. PMID- 3349267 TI - Unilobar enlargement of normal thymus gland causing mass effect. PMID- 3349268 TI - Aneurysm of an aberrant right subclavian artery. PMID- 3349269 TI - Spasm of the deep circumflex artery causing entrapment of a guidewire. PMID- 3349270 TI - Changes of cerebral air embolism shown by computed tomography. PMID- 3349271 TI - Three-dimensional computed tomographic reformations of intracranial vascular lesions. PMID- 3349272 TI - The calculation of absorbed doses for radiobiological studies involving the use of small irradiation fields. PMID- 3349273 TI - Predicted allowable doses to normal organs for biologically targeted radiotherapy. PMID- 3349274 TI - Case of the month. The dry tap. PMID- 3349275 TI - Hypothermic hyperbaric irradiation. PMID- 3349276 TI - The role of magnesium in calcium oxalate urolithiasis. AB - The aim of this study was to evaluate the effect of magnesium on calcium oxalate crystal formation, both in physiological conditions and at slightly higher oxalate concentrations, using a mixed suspension mixed product removal crystallizer and scanning electron microscopy. True supersaturation ratios were calculated by allowing for complexation in solution. Magnesium inhibited the nucleation rate at all oxalate concentrations. It also inhibited the growth rate at oxalate concentrations of less than approximately 2.0 mmol/l but promoted the growth rate at higher concentrations. This suggests that, provided the oxalate concentration is sufficiently high, increase of magnesium concentration can increase the crystal growth rate. At physiological concentrations of oxalate, however, magnesium decreases both nucleation and growth rates. The SEM photographs showed that the predominant crystal was calcium oxalate trihydrate at low magnesium concentrations, with calcium oxalate dihydrate being observed in larger quantities at high magnesium concentrations. PMID- 3349277 TI - Grading in superficial bladder cancer. (1). Morphological criteria. AB - In a prospective study on the grading of superficial papillary neoplasms of the bladder a distinction was made between tumours showing only increased cellularity without appreciable cellular and nuclear deviation (grade 1), tumours showing slight cellular variation (grade 2a), and tumours showing clear cytological deviation and a tendency to lose normal polarity (grade 2b). Ninety-one patients with a superficial tumour were followed up for a mean of 24 months. Grade 2a tumours recurred later and in fewer patients than grade 2b tumours. Progression was seen in 4% of grade 2a tumours and in 33% of grade 2b carcinomas. Adapting our results to the WHO grading system, we suggest that all tumours in this study defined as grades 1 and 2a should be classified as low grade and tumours defined as grade 2b should be classified as intermediate grade. PMID- 3349278 TI - Grading in superficial bladder cancer. (2). Cytogenetic classification. AB - Cytogenic analysis was performed in 92 newly diagnosed transitional cell bladder carcinomas and the results were correlated with the clinical course in superficial tumours. Low grade tumours appeared to have hypodiploid or peridiploid chromosomal numbers. Intermediate grade tumours were characterised by chromosomal counts up to the hyperdiploid range but could have a peridiploid modal number. In high grade tumours the modal number was hyperdiploid. The range in chromosomal counts appeared to be more reliable than the modal number as a predictor of the course of superficial tumours. The significant difference in chromosome numbers between low, intermediate and high grade tumours indicates that grading reflects major cytogenetic changes in the tumour cells. PMID- 3349280 TI - Torsion of scrotal contents in children. AB - One hundred and forty consecutive cases of torsion of scrotal contents were reviewed retrospectively. There were 95 cases of torsion of the testicular appendage and 45 cases of testicular torsion. Testicular torsion was more common on the left and patients tended to present earlier with more systemic upset in the form of vomiting, abdominal and groin pain than patients with torsion of a testicular appendage. Pathognomic features of examination were an elevated or ectopic testis in 50% of cases of testicular torsion and a palpable tender blue nodule in 21% of cases of torsion of a testicular appendage. We believe that it is often possible to distinguish between these two conditions and, where this is possible, a trial of conservative management is justified for torsion of a testicular appendage. PMID- 3349279 TI - Subcapsular orchiectomy under local anaesthesia. Technique, results and implications. AB - One hundred patients with carcinoma of the prostate have been treated by bilateral subcapsular orchiectomy under local anaesthesia over a 5-year period. The indications, technique and results of performing the operation in this way are described. The procedure is simple, effective and well tolerated by the patients. PMID- 3349282 TI - Adenocarcinoma of the bladder 29 years after ileocystoplasty. PMID- 3349281 TI - Comparison of in vitro encrustation on silicone and hydrogel-coated latex catheters. AB - Mid-shaft sections of 100% silicone (Bardex) and hydrogel-coated latex (Biocath) catheters were subjected to controlled in vitro encrustation conditions for periods of up to 18 weeks. There was no significant difference in the quantities of encrusting deposits formed on these two materials during the course of the experiment. PMID- 3349283 TI - Inverted papilloma and papillary transitional cell carcinoma of bladder. PMID- 3349284 TI - Solitary cutaneous metastasis from transitional cell carcinoma of the bladder. PMID- 3349286 TI - Prazosin-induced priapism. Pathogenic and therapeutic implications. PMID- 3349285 TI - Adenocarcinoma of the caecum occurring in a caecocystoplasty. PMID- 3349287 TI - Allergic reaction to intravesical adriamycin. PMID- 3349288 TI - Retrocaecal peri-appendicular abscess simulating right ureterolithiasis. PMID- 3349290 TI - re Fluid absorption during urological endoscopy. PMID- 3349289 TI - Penile denervation. PMID- 3349291 TI - Prospective study of conservative and operative treatment for faecal incontinence. AB - To assess the functional results of treatment of faecal incontinence we carried out physiological and radiological measurements in 46 patients and 20 controls. Twenty patients were selected for conservative treatment and 26 for surgery (including 17 postanal repairs and 6 anterior sphincter repairs). The degree of incontinence was scored before and after treatment and postoperative investigations carried out on 17 patients (11 postanal repairs). Forty per cent of the conservative treatment group had a successful result compared with sixty five per cent of the operative group as a whole and fifty-nine per cent of the postanal repair patients. Resting and 'squeeze' anal canal pressures were improved following postanal repair as was upper anal canal sensation but there was no change in the anorectal angle. We conclude that the anorectal angle is not crucial in maintaining continence. PMID- 3349292 TI - Gastric cancer: an audit of 122 consecutive cases and the results of R1 gastrectomy. AB - In a consecutive series of 122 patients with gastric carcinoma, 9 per cent had no operation, 27 per cent had incurable disease at laparotomy, and 64 per cent underwent gastric resection. R1 gastrectomy was performed in 73 of the 78 resections. The operative mortality after gastric resection was 4 per cent, but there were no deaths after potentially curative resections. The actuarial 5-year survival was 20 per cent overall, 60 per cent in patients undergoing a 'curative' resection with N0 disease, and 18 per cent in patients with N1 disease. Local or regional recurrence without evidence of distant metastases was identified in 11 per cent of cases after 'curative' resections. The probability of survival was adversely affected by N1 nodal involvement (P less than 0.005) and by the presence of poorly differentiated or anaplastic tumours (P less than 0.001). Only 6 per cent of patients had early gastric cancer, and absolute curative resections by Japanese criteria were possible in only 5 per cent of cases. The results suggest that the unfavourable presenting pathology is the principal determinant of the poor prognosis of gastric cancer. A more radical or extended lymphadenectomy (R2/3 gastrectomy) might have cured more patients with N1 metastases, but only 12 per cent of potentially curable patients had N1 disease in this study, and it appears that more radical surgery may have little effect on the overall survival rates for gastric cancer. PMID- 3349293 TI - Randomized comparison of R1 and R2 gastrectomy for gastric carcinoma. AB - The contention that the R2 radical gastrectomy for localized and potentially curable gastric carcinoma may be superior to gastrectomy without lymphadenectomy (R1) was assessed by randomized trial. Five years after commencement 403 patients have been evaluated at surgery and only 43 (11 per cent) found eligible (S0-2, P0, H0, N0-1), 22 of whom underwent R1 and 21 R2 gastrectomy. Seven patients had final histological stages in excess of the protocol. The R2 group had a longer operating time (P less than 0.005), a greater blood transfusion requirement (P less than 0.005), a longer hospital stay (0.05 greater than P greater than 0.025) and required reoperation in four cases. There were no postoperative deaths. Four patients have died from the disease in the R1 group and five in the R2 group, there being no difference in the probability of survival at a median follow-up of 3.1 years. The small proportion of patients suitable for radical R2 surgery, the high associated morbidity and the fact that survival advantage has yet to be proven in trial suggest that this procedure should not yet be performed outside of controlled clinical trials. PMID- 3349295 TI - A rational technique for surgical operation on Borrmann type 4 gastric carcinoma: left upper abdominal evisceration plus Appleby's method. AB - Borrmann type 4 gastric carcinoma, including linitis plastica, is difficult to detect at an early stage and the results of surgical treatment remain poor. We have used 'left upper abdominal evisceration plus Appleby's method (LUAE + Apl.)' as a radical surgical procedure for this disease. During the period 1983-86, 30 cases of Borrmann type 4 gastric carcinoma underwent this procedure (Group A). These cases were compared with 30 patients who underwent total gastrectomy with pancreaticosplenectomy (Group B) during the period 1980-82. Although this is not a randomized study and the extent of resection was greater in Group A, the operation time, amount of blood loss, and number of complications were similar for both methods. When the survival rates were compared, the 3-year survival rate in stage II-III cases was higher for Group A (83.3 per cent) than for Group B (42.2 per cent) (P less than 0.05). One patient in Group A and 12 patients in Group B died with peritoneal metastasis within 3 years of operation in stage II III. The LUAE + Apl. method is a rational and useful technique for the surgical treatment of Borrmann type 4 gastric carcinoma. PMID- 3349294 TI - Experimental columnar metaplasia in the canine oesophagus. AB - Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic. PMID- 3349296 TI - Isolated pyloric obstruction in association with large hiatus herniae. PMID- 3349297 TI - Anterior lesser curve seromyotomy with posterior truncal vagotomy versus proximal gastric vagotomy. AB - In a prospective randomized trial anterior lesser curve seromyotomy with posterior truncal vagotomy (ASPTV, n = 48) has been compared with proximal gastric vagotomy (PGV, n = 43). Eighty-eight and eighty-three patients were available for follow-up studies at 1 year and 2 years, respectively. Six months postoperatively the mean reduction in pentagastrin-stimulated peak acid output (PAO) was 48.5 per cent (s.d. 26.3) after PGV and 50.5 per cent (s.d. 23.3) after ASPTV. Two years after the operation satisfactory clinical results (Visick I + II) were found in 84.2 per cent of the patients after PGV and in 88.9 per cent after ASPTV. There was a significant difference in the duration of surgery. No serious postoperative gastric sequelae were encountered after either operation. Up till January 1987, eight endoscopically proven, symptomatic recurrent ulcers have been diagnosed: four in the PGV group (9.3 per cent) and four in the ASPTV group (8.7 per cent). The results of this randomized study suggest that ASPTV is as good as PGV in the surgical treatment of chronic duodenal ulcers. PMID- 3349298 TI - Stimulation of the healing of experimental colon anastomoses by low-power lasers. AB - Anastomotic leakage following colorectal surgery remains a complication with high mortality and morbidity. Recent studies suggest that helium-neon (He-Ne) lasers at specific energy densities can be used to enhance wound healing in different tissues. In this experimental study we have tested the strength of end-to-end anastomosis of the rat colon irradiated by He-Ne laser by measuring bursting pressures and bursting wall tensions at 2, 4 and 7 days after operation. The study shows that He-Ne laser radiation induces a significant increase in colonic strength at the anastomosis. The laser does not cause the luminal narrowing observed in non-irradiated specimens. PMID- 3349299 TI - Cytotoxic-loaded albumin microspheres: a novel approach to regional chemotherapy. AB - Adriamycin-loaded albumin microspheres (15-40 micron diameter) incorporating 1 per cent by weight of Adriamycin were prepared by cross linking albumin with glutaraldehyde. After systemic administration in rats, the microspheres were trapped in the pulmonary capillary bed, biodegradation occurring over 48 h. After selective intrarenal arterial injection of 99mTc-labelled albumin microspheres in rabbits, 97 per cent of the injected microspheres were trapped within the kidney; less than 1 per cent were found in the contralateral kidney, lungs and liver. Similar results were obtained after selective intrahepatic arterial injection. The selective injection of cytotoxic-loaded microspheres may provide a reliable method of administering high concentrations of cytotoxic drug to a target organ without producing high serum levels; this technique may have a role in the management of solid tumours. PMID- 3349300 TI - Wound healing response in surgical patients: recent food intake is more important than nutritional status. AB - We have recently found that an impairment of the wound healing response (WHR) occurs in surgical patients with protein-energy malnutrition before there are any measurable changes in body fat and protein stores. The hypothesis of this study was that the patients' recent food intake is more important in determining the WHR than the patients' overall nutritional status. We have measured the recent food intake (by dietary recall), the WHR (by hydroxyproline accumulation in subcutaneous GORE-TEX implants), the pre-operative weight loss (per cent), and body fat and protein stores (by in vivo neutron activation analysis) in 83 patients awaiting a major elective gastrointestinal resection, and divided them into two groups: adequate recent food intake (n = 59) and inadequate recent food intake (n = 24). There was no significant difference between these two groups for age, sex, diagnosis, surgical procedure, weight loss (per cent), or the amount of body fat and protein stores but there was a significant difference in the WHR (1.81 +/- 0.16 s.e.m. versus 1.04 +/- 0.22 s.e.m. nmol hydroxyproline/mg GORE TEX, P less than 0.005). These results show that pre-operative food intake has a greater influence over the wound healing response than absolute losses of protein and fat from body stores and they suggest that the maintenance of a normal food intake up until the time of surgery is of importance in preventing an impairment of the wound healing response. PMID- 3349301 TI - Urgent and early cholecystectomy for acute gallbladder disease. AB - A retrospective study of 645 cholecystectomies performed in a surgical unit over a 10-year period is presented, of which 236 were carried out during an acute admission. Of these 236 cholecystectomies, 195 were performed for acute cholecystitis and 41 for acute gallstone pancreatitis. In the acute cholecystitis group the proportion of patients over 70 years of age was significantly higher (35 per cent) than the corresponding elective group (10.3 per cent). Of those patients presenting with complications (empyema, gangrene, perforation, and biliary peritonitis) 51 per cent were over the age of 70 years. The most valuable investigation in the diagnosis of acute cholecystitis was ultrasound carried out within the first 48 h, with positive results in 83 per cent of those examined. The mortality for elective cholecystectomy was 0.5 per cent rising to 4.7 per cent in the urgent/early cholecystectomy group. The mean age of the 11 patients who died was 76 years, 8 of these patients being over the age of 70 years. The mortality in the subgroup of patients over 70 years was 10 per cent rising to 20 per cent in the over-80 age group. There were no deaths in the acute gallstone pancreatitis group. We conclude that emergency or early cholecystectomy is a safe procedure in patients under 70 years of age. However, patients over 70 years present with more serious complications of acute gallbladder disease which necessitate urgent surgery. We therefore recommend early cholecystectomy in patients over 70 years despite the high attendant mortality. PMID- 3349302 TI - Non-invasive treatment for retained common bile duct stones in patients with T tube in situ: saline washout after intravenous ceruletide. AB - The combination of ceruletide-induced relaxation of the sphincter of Oddi plus flushing with saline has recently been proposed as a novel procedure for the treatment of residual common bile duct (CBD) stones. In this study we have administered intravenous ceruletide (2 ng kg-1 body weight min-1 for 1 h) plus intraductal saline (800-3000 ml, infused at a rate that kept biliary pressure below 30 cmH2O) to a group of 14 patients. The treatment induced the passage of residual stones in 11 subjects (79 per cent) with complete clearance in 7 (50 per cent). The majority of the cleared concretions (11/15) had a diameter less than 10 mm. No severe side-effects were recorded during the treatment. Four of the seven subjects who exhibited incomplete CBD clearance underwent a short cycle of mono-octanoin administration in order to reduce the size of residual radiolucent stones. This course of treatment was followed by another attempt with intravenous ceruletide and saline washout which gave a successful response in an additional three cases. These data indicate that the combination of ceruletide and flushing is a safe and inexpensive method for treatment of residual stones. The procedure is feasible for both radiolucent and radio-opaque stones and is mainly eligible for small concretions of diameter less than 10 mm. Larger (greater than 10 mm) radiolucent stones may be partially dissolved with mono-octanoin and then eliminated by the washout technique. PMID- 3349303 TI - Anergy in jaundiced patients. AB - A prospective study of delayed hypersensitivity was carried out in jaundiced patients. One hundred and nineteen subjects were studied. Fifty-nine were controls and sixty were patients with pancreatobiliary pathology and biliary tract obstruction. A Multitest technique was used to evaluate the delayed hypersensitivity response, classifying the subject into one of three groups: immunocompetent, relatively anergic and anergic. In the control group, 76 per cent of the subjects were immunocompetent as opposed to 17 per cent of the patients (P less than 0.001). Ten per cent of the control subjects and fifty-five per cent of the patients presented anergy (P less than 0.001). Amongst the patients no difference could be found in the index of anergy between malignant or benign pathology. A greater incidence of postoperative septic complications in anergic and relatively anergic patients was found. Our study indicates a relationship between jaundice and anergy. PMID- 3349304 TI - Peroperative cholangiography: needle puncture of the hepatic duct versus cannulation of the cystic duct. PMID- 3349305 TI - Operative management of tubulovillous neoplasms of the duodenum and ampulla. AB - Six patients are described to illustrate the operative management of tubulovillous neoplasms of the duodenum. Pancreaticoduodenectomy is appropriate for associated invasive carcinoma. Transduodenal submucosal excision of tubulovillous neoplasms with resection and reconstruction of the distal bile and pancreatic ducts if necessary is a satisfactory alternative when the neoplasm has not penetrated the muscularis mucosae. PMID- 3349306 TI - Rupture of abdominal hydatid cysts. PMID- 3349307 TI - Surgery in tropical pancreatitis. AB - Nineteen consecutive patients with tropical pancreatitis and chronic pancreatic pain operated upon over a 3-year period in Kerala, India, are reported. The pancreatic ductal morphology was studied by ultrasound scan, endoscopic retrograde cholangiopancreatography and/or operative pancreatography. In 17 patients, duct drainage by lateral pancreatojejunostomy and/or transduodenal pancreatic sphincteroplasty constituted the main surgical procedure. Caudal pancreatic resection was required in six of these patients. Unresectable pancreatic masses were found in two patients. Three patients died. Of the 16 survivors, 14 had good relief of pain within the limits of the available follow up. In analysing the results, patients with 'obstructive pancreatitis' were found to have increased morbidity and mortality. The need to diagnose this subgroup of chronic pancreatitis pre-operatively is discussed. PMID- 3349308 TI - Pancreatic trauma: acute and late manifestations. AB - A retrospective analysis of 47 patients with pancreatic trauma is presented. A total of 43 patients presented with acute pancreatic injury, 32 after blunt abdominal trauma. Isolated blunt pancreatic injuries were a considerable diagnostic problem with a mean delay from trauma to operation of 9.4 days. At operation peripancreatic drainage in mild injuries and distal resection in cases of ductal injury were the commonest procedures. The overall mortality was 19 per cent, but only three of the eight deaths were attributable to the pancreatic injury. The overall complication rate was 63 per cent and the pancreatic complication rate was 33 per cent. Four patients presented with chronic pancreatitis resulting from previously untreated blunt abdominal trauma 0.5-21 years earlier. Clinically, they did not differ from the manifestations of chronic pancreatitis of other aetiological origins. PMID- 3349310 TI - Surgical gloves as a mechanical barrier against human immunodeficiency viruses. AB - A wide variety of surgical gloves are presently available. Seven different types of gloves were investigated for the ability to prevent transmission of the human immunodeficiency virus (HIV), the causative agent of AIDS. Six types of gloves withstood severe compression tests and also exhibited direct antiviral properties. No penetration of HIV through the intact glove was detected. PMID- 3349309 TI - Staphylococcus epidermidis as a cause of postoperative wound infection after cardiac surgery: assessment of pathogenicity by a wound-scoring method. AB - Wound infection after clean surgery prolongs hospital stay but the organism most commonly isolated from wound discharge, Staphylococcus epidermidis, is often dismissed as a contaminant or commensal. The wounds of 517 patients were assessed, after cardiac surgery, by a wound-scoring method ('ASEPSIS') and a close comparison was made of the appearance and clinical outcome of 89 wounds, from which bacteria were isolated. There was no significant difference in the scores of 49 wounds, where S. epidermidis was the sole isolate (9.5 per cent of all wounds, 95 per cent CI 6.9-12.0 per cent), and 13 wounds infected with Staphylococcus aureus (2.5 per cent, 95 per cent CI 1.2-3.9 per cent). Repeat cultures were obtained from 21 of the 49 wounds and, in 16 of these, the second isolate showed the same biochemical reactions and antibiotic resistance pattern as the first. Infection of sternal wounds is commoner with coagulase-negative staphylococci than with S. aureus and, clinically, is just as severe. PMID- 3349311 TI - Aggressive treatment of severe diffuse peritonitis: a prospective study. AB - In a prospective study of 22 patients with diffuse peritonitis managed by the method of electively staged multiple laparotomies, the abdomen was left open in 9 patients. The patients were selected on the basis of the severity of their intra abdominal infection: only massive faecal peritonitis, postoperative peritonitis and pancreatic abscesses were included. These amounted to only 9 per cent of all patients with intra-abdominal infection treated over a 2-year period. Up to seven re-operations were required per patient. In view of a high mortality rate of 32 per cent, the superiority of this aggressive management strategy over conventional methods is not fully established. PMID- 3349312 TI - Approach to ingrowing toenails: the wedge resection/segmental phenolization combination treatment. AB - One hundred and seventy procedures were performed on one hundred and forty patients with ingrowing toenails. Each patient was randomly allocated to one of three treatment groups. There were 55 wedge resections (WR), 53 segmental phenolizations (SP) and 62 wedge resection/segmental phenolization combination treatments (WR/SP). All patients were followed up for 6 months. The duration and intensity of postoperative pain was assessed and the recurrence rate monitored. Postoperative pain was less in the WR/SP group (9.4 +/- 13.5 h) than in the WR group (30.0 +/- 37.6 h, P less than 0.001). There were seven recurrences in the WR group, four in the SP group, and none in the WR/SP group. The results in the WR/SP group were statistically significant when compared with the WR group (P less than 0.01) and with the SP group (P less than 0.05). We conclude that the WR/SP combination procedure is a superior form of treatment for ingrowing toenails. PMID- 3349314 TI - Hormonal manipulation in the treatment of pancreatic carcinoma. PMID- 3349313 TI - Smooth muscle tumours of the digestive tract: report of 160 cases. AB - Of 160 patients seen in the period 1951-84 with smooth muscle tumours of the digestive tract, 71 proved to have leiomyomas, 87 had leiomyosarcomas and 2 had leiomyoblastomas. Tumour diameter was frequently greater in patients with leiomyosarcoma. The surgical mortality was 2.8 per cent after treatment of leiomyoma and 10.3 per cent after treatment of leiomyosarcoma. After resection of leiomyosarcoma the 2-year survival rate was 86 per cent and the 5-year survival rate was 43 per cent. The only hope of cure of these malignant lesions lies in surgical resection but, even when the lesion is incurable, resection may allow worthwhile palliation. PMID- 3349315 TI - Peptic ulcer surgery and colorectal cancer risk. PMID- 3349316 TI - Pre-operative assessment of fitness score. PMID- 3349317 TI - 'Skew flap' below-knee amputation. PMID- 3349318 TI - Radionuclide ejection fraction. PMID- 3349319 TI - Wound healing. PMID- 3349320 TI - Controlled trial of occlusive dressings in healing chronic venous ulcers. PMID- 3349321 TI - Publication lag times in surgical journals. PMID- 3349322 TI - Biliary lithiasis in the elderly. PMID- 3349323 TI - Review of a hospital experience of breast abscesses. PMID- 3349324 TI - Localization studies in patients with primary hyperparathyroidism. PMID- 3349325 TI - Gastric varices: a proposed classification leading to management. PMID- 3349326 TI - Necrosectomy and postoperative local lavage in necrotizing pancreatitis. AB - Necrosectomy with postoperative continuous local lavage was performed in a prospective study involving 95 patients with necrotizing pancreatitis. In the same period 567 patients with oedematous-interstitial pancreatitis were treated non-operatively with a hospital mortality rate of 0.7 per cent. In patients with necrotizing pancreatitis the median Ranson criteria score was 4.5 points; operation was required at a median of 7 days after the onset of symptoms because of non-response to conservative treatment. In all, 59 per cent of the patients (56 out of 95) developed extended intrapancreatic parenchymal necrosis, 70 per cent had ascites, and 66 per cent had intra- and extrapancreatic necrosis; 42 per cent of the patients had bacterial infection of the necrotic tissue. For lavage a median of 8 l/24 h of fluid were instilled postoperatively for 25 days (median). The lavage fluid showed high levels of immunoreactive trypsin, phospholipase A2, and endotoxin in the early postoperative period. Hospital mortality rate was 8.4 per cent. Necrosectomy and continuous postoperative lavage can achieve high survival rates in patients with necrotizing pancreatitis. Postoperative local lavage allows the continuous non-operative evacuation of biologically active compounds and devitalized tissue, and avoids damage to remaining vital exocrine and endocrine pancreatic tissue. PMID- 3349328 TI - Surgical morbidity and mortality in one hundred and twenty-nine patients with obstructive jaundice. AB - One hundred and twenty-nine jaundiced patients were operated upon for the relief of benign and malignant bile duct obstruction during a 10-year period, 1977-86. The overall mortality was 4.7 per cent but increased to 9.1 per cent in patients with a serum bilirubin greater than 300 mumol/l. In all, 46.5 per cent of patients had a rise in postoperative creatinine but renal dysfunction occurred in only 4.7 per cent. Wound infection developed in 3.1 per cent of patients and appeared unrelated to infected bile; 3.9 per cent of patients were treated for postoperative septicaemic episodes. The low morbidity and mortality observed suggests that preoperative biliary drainage need not be considered in routine surgical practice if simple measures to maintain urine flow and prevent postoperative sepsis are used. PMID- 3349327 TI - Patient controlled analgesia and urinary retention. PMID- 3349329 TI - Pancreaticogastrostomy: the preferred operation for pain relief in chronic pancreatitis. AB - We present the results of surgery in 53 patients with intractable pain due to chronic pancreatitis associated with pancreatic duct dilatation. Using a limited mucosal to mucosal anastomosis over a silastic T tube the main pancreatic duct was drained in 33 patients into a Roux-en-Y jejunal loop (pancreaticojejunostomy, PJ) and in 20 patients into the stomach (pancreaticogastrostomy, PG). There was one postoperative death in the PJ group and none in the PG group. All patients were followed up for a minimum of four years. There was significantly greater pain relief in the PG group both at 1 (P less than 0.01) and 4 years (P less than 0.05) after surgery. We argue that PG is the operation of choice to relieve intractable pain in most patients with chronic pancreatitis associated with duct dilatation. PMID- 3349330 TI - Management of penetrating abdominal stab wounds. AB - The authors present the results of a therapeutic trial of the conservative or surgical management of penetrating abdominal stab wounds (PASW) based on clinical criteria. In a prospective series of 100 patients, 70 were treated non operatively. Thirty patients were operated upon, twenty-one immediately and nine during the 48 h observation period. In five laparotomies no significant injuries were found. Morbidity was similar in both immediate and delayed laparotomy groups (3/21 versus 1/9). Acute alcoholic intoxication identifies a subgroup of patients that are difficult to evaluate and hence are more likely to be managed by laparotomy (chi 2 = 4.056, P less than 0.05). The authors conclude that selective surgical management of PASW based on clinical criteria is an accurate and safe procedure. PMID- 3349331 TI - True radial artery aneurysm. PMID- 3349332 TI - Surgical approaches to vertebral artery injuries. AB - Twenty patients with penetrating injuries of the vertebral artery who were treated as emergencies were subjected to the following operative approaches: five cases, Henry's approach (posterior) and modified Henry's approach (anterior); five cases, limited exposure and application of metal clips; four cases, plugging of the arterial defect with Oxycell or crushed muscle; three cases, control with ligatures and non-conventional exposure of the artery; one case, inflation of a balloon catheter within the vertebral canal; one case, repair of the lacerated first extraosseous part of the vertebral artery. One patient died from exsanguination on the operating table, before any repair was possible. The overall mortality was 20 per cent and the mean hospital stay 6.1 days. Thirty five per cent of the patients presented with neurological complications, and 55 per cent left the hospital well. No advantage of Henry's classical approach over limited exposure and control with metal clips was shown, when mortality, hospital stay and long-term problems were compared. Because of its relative simplicity we suggest that the metal clipping of the vertebral artery, above and below the site of injury, is an effective technique that can be used to stop the bleeding. One case presented as a false aneurysm of the vertebral artery, following a stab wound. This was successfully treated with excision of the aneurysm and vertebrovertebral artery bypass, using a saphenous vein graft. PMID- 3349333 TI - Venous mesenteric infarction: a particular entity. AB - Ninety-eight patients with documented mesenteric infarction during a 19-year period were reviewed. In 13 patients infarction was due to a mesenteric venous thrombosis (MVT). Patients with MVT distinguished themselves from those having another aetiology by: (1) longer history of pain before admission (median 8 days, P less than 0.0001); (2) typical appearance of the bowel at laparotomy (10/13); (3) a localized segment of ischaemic jejunum or ileum of less than 120 cm in length (12/13) allowing better operability at the first laparotomy (P = 0.006). In hospital the mortality was lower for venous mesenteric infarction (5/13, 38 per cent) than for mesenteric infarction of other aetiologies (70/85, 82 per cent) (P = 0.002). Patients with primary venous mesenteric infarction showed a better survival rate (one death in eight patients) than patients with associated diseases such as liver cirrhosis, sepsis or previous operation who had a poor prognosis with a mortality comparable to other aetiologies of acute bowel ischaemia (four deaths in five patients). Since the high recurrence rate of this disease in the early postoperative period was due to residual venous thrombosis and to a hypercoagulable state, a wide bowel resection is recommended followed by early and long-term anticoagulation. Thrombectomy is probably inefficient since it removes only centrally located thrombi and leaves peripheral occlusion, which is responsible for the recurrence. PMID- 3349334 TI - Fate of the ischaemic limb in Buerger's disease. AB - The clinical course of 328 patients with Buerger's disease (thromboangiitis obliterans: TAO) was followed. Neither ischaemic ulcers nor gangrene occurred in 26 per cent of the patients. Almost all of the ulcers occurred in patients between 20 and 50 years of age, with a peak incidence between 40 and 45 years. The younger the patient at the onset of the disease, the later the first ulcer occurred, and the later the first ulcer occurred, the shorter the period in which ulceration may recur. Recurrent ulcers were observed in 45 per cent of the patients. The progression of symptoms was influenced by smoking, but this was not the only deleterious factor as there were patients with stable TAO unaffected by smoking. In the 30 patients over the age of 60 years, ulceration and gangrene were not observed. In all patients, the progression of symptoms was self-limited and recurrent ulcers occurred less frequently with ageing. The rate of major amputation was low (3.9 per cent) although minor digital amputations were sometimes required. The survival rate of patients with TAO was higher than that of patients with arteriosclerosis obliterans. The aim of treatment in patients with TAO is to make patients abstain from smoking to prevent ulceration and to shorten the period of healing of trophic lesions without major amputation, as ulceration and gangrene in T AO are limited to the most distal part of the limbs, and seems to have healing potential. PMID- 3349335 TI - Small bowel obstruction due to peritoneal encapsulation. PMID- 3349336 TI - Recurrent inguinal hernia: a personal study. AB - A personal series of 287 recurrent inguinal hernias repaired by a single consultant surgeon is presented. Four techniques of repair were employed in the series: Bassini operation; a posterior 'lace repair'; complete closure of the canal after division of the spermatic cord and local repair of isolated defects. The overall recurrence rate, 27 failures in 287 operations (9 per cent) is disappointing. The best technique is excision of the cord and canal closure, two failures in 43 operations (5 per cent). Cord excision does carry a risk of testicular complications. PMID- 3349337 TI - Diagnosis of Meleney's synergistic gangrene. AB - A retrospective and comparative study of 127 case reports of Meleney's postoperative progressive synergistic gangrene and of 62 examples of postoperative amoebic skin gangrene, showed that these two entities were clinically indistinguishable and that therefore a purely clinical diagnosis of Meleney's gangrene could not be made. Furthermore, a critical appraisal of the bacteriological data indicated that a certain diagnosis of Meleney's gangrene cannot be provided by the clinical bacteriologist. Finally, the histological features were entirely non-specific thus precluding a definitive diagnosis by the histopathologist. If Meleney's entity cannot be diagnosed its existence becomes debatable. The alternative diagnosis of cutaneous amoebiasis is advanced for consideration. Several of the outstanding features of Meleney's progressive gangrene, hitherto unexplained, are better understood if Entamoeba histolytica is accepted as the prime cause rather than bacteria. PMID- 3349338 TI - Gastric outlet loss and enterogastric reflux after gastrectomy. AB - The relationship of gastric secretion in response to a single injection of insulin and in response to a histamine infusion, before and after partial gastrectomy, was analysed in 58 patients. The aspirated gastric juice was corrected for gastric outlet loss and enterogastric reflux. Gastrectomy drastically reduced the stimulated gastric secretion by a similar proportion for the two secretagogues, thereby implying that antral gastrin plays no greater part in one than in the other. Gastric outlet losses were also reduced after gastrectomy, but as a fraction of gastric contents, both gastric outlet loss and enterogastric reflux more than doubled; the possible relationship of these findings to the aetiology of gastric ulcer is discussed. PMID- 3349339 TI - Treatment policy for the management of carcinoma of the oesophagus. AB - The management of 120 consecutive patients with carcinoma of the oesophagus, treated in a district general hospital over a 10-year period is reviewed. The treatment options were by endoscopic methods, radiotherapy, surgery or a combination of these. Adenocarcinoma was the most frequent histological type (51 per cent) and 41 per cent of patients had squamous carcinoma. In addition to survival the quality of swallowing and the incidence of late complications following the treatment options was assessed. Primary surgery was carried out in 21 cases (operability rate 17.5 per cent) and 81 per cent of these cases were resectable. The overall operative mortality rate was 14.3 per cent (6 per cent in resected cases) and the 5-year survival rate was 9.5 per cent. After primary radiotherapy only 5 per cent of patients survived 2 years. The majority of patients were treated by endoscopic intubation with an overall mortality of 16.6 per cent and a mean survival of 5.5 months. Patients treated surgically experienced the best symptomatic relief and had the lowest incidence of late complications, when compared with those treated differently. However the overall results of surgery were poor and there remains the need to compare the results of surgery and radiotherapy in similar groups of patients. PMID- 3349341 TI - Autotransplantation of lingual thyroid into the neck. PMID- 3349340 TI - Relationship between gastric emptying of liquid and postvagotomy diarrhoea. AB - Gastric emptying of liquid was studied in 10 normal volunteers and in 27 patients previously treated with truncal vagotomy and drainage. Thirteen of the twenty seven patients complained of persistent postvagotomy diarrhoea. For each study 300 ml 15 per cent dextrose, labelled with 99mTc-diethylene triamine penta-acetic acid (DTPA), was ingested at a standard rate by subjects who sat facing a gamma camera. Imaging proceeded for 30 min. Gastric area activity curves were corrected for emptying of the test meal during ingestion, and for movement using a new image alignment technique. Gastric emptying at 15 min was 10 +/- 2.6 per cent (mean +/- s.e.m.) in healthy volunteers, 48 +/- 7.3 per cent in patients without diarrhoea, and 84 +/- 2.3 per cent in those with diarrhoea (P less than 0.001, ANOVA). Gastric emptying from 15 min onwards was slower than normal in both patient groups (P less than 0.001). These results show that initial gastric emptying is rapid following truncal vagotomy and drainage, and this change is greater in patients with postvagotomy diarrhoea. No patient with diarrhoea had normal initial gastric emptying. PMID- 3349342 TI - Omental abscess: a rare complication after implantation of autologous splenic tissue into the omentum. PMID- 3349344 TI - Parietal cell vagotomy. PMID- 3349343 TI - Colitis cystica profunda of the rectum treated by mucosal sleeve resection and colo-anal pullthrough. PMID- 3349345 TI - Sodium nitroprusside induced hypotensive anaesthesia for reducing blood loss in patients undergoing lienorenal shunts for portal hypertension. PMID- 3349347 TI - Urethral versus suprapubic catheterization. PMID- 3349346 TI - Management of periampullary carcinoma. PMID- 3349348 TI - Percutaneous oxygen tension. PMID- 3349349 TI - Synchronous colorectal carcinomas. PMID- 3349350 TI - Pain scores in haemorrhoidectomy. PMID- 3349351 TI - Services for sickle cell disease: unified approach needed. PMID- 3349352 TI - Pure trigeminal motor neuropathy. PMID- 3349353 TI - Retinal projections in two Australian polyprotodont marsupials: kowari, Dasyuroides byrnei, and fat-tailed dunnart, Sminthopsis crassicaudata (Dasyuridae). AB - Retinal projections were examined in two small dasyurids, the kowari and the fat tailed dunnart, following injections of 3H-proline into one eye. In both animals retinal fibres terminate in the dorsal and ventral lateral geniculate nuclei (LGd, LGv), the lateral posterior nuclear complex, the pretectum, the superior colliculus, the suprachiasmatic nucleus of the hypothalamus and the nuclei of the accessory optic system. The lateroposterior thalamic complex and the accessory optic nuclei receive projections from the contralateral eye only; the remaining centres receive bilateral inputs. Both LGd contain an undifferentiated beta or medial segment and an alpha or lateral segment that comprises further cellular sublaminae, 4 in the kowari and 3 in the dunnart. There is substantial overlap of crossed and uncrossed terminals in both segments, though in each animal a narrow cell lamina next to the optic tract receives only crossed projections and the lateral part of the beta segment receives only uncrossed projections. There is a cell-sparse zone within the alpha segment that receives a predominately uncrossed projection in the kowari and a crossed projection in the dunnart. In both marsupials the density of crossed and uncrossed terminals is equal, a feature of dasyurid quolls but not of another dasyurid, the Tasmanian devil. Additionally, retinal terminals do not form dense clusters within the LGd neuropil. This feature is characteristic of quolls, but not of other mammals, marsupial or placental, all of which display LGd terminal clusters. These findings suggest that the functional organisation of the LGd in these dasyurids may differ from that found in other marsupials. PMID- 3349354 TI - [Fasciculations and muscular pain connected with the use of suxamethonium]. PMID- 3349355 TI - [Postoperative analgesia by ketoprofen perfusion in osteoarticular surgery]. AB - Post operative pain is a constant and deleterious factor, resulting from surgical traumatism of the operated tissues; this aggression leads to a local inflammatory and painful reaction mediated by prostaglandins. Non steroid anti-inflammatory drugs inhibit their synthesis. In this study, ketoprofene appears to be an interesting treatment of post operative pain especially in orthopedic and traumatologic surgery. PMID- 3349356 TI - [Intravenous loco-regional anesthesia with 0.5% lidocaine. Apropos of 364 cases of surgery of the upper limb]. PMID- 3349357 TI - [Anesthesiology practice and medicolegal consequences of the complications of anesthesia in Sweden]. PMID- 3349358 TI - [Late obstruction of respiratory airways after tracheal intubation]. PMID- 3349360 TI - Closed-angle glaucoma in 20 pairs of twins. AB - Two pairs of twins with chronic closed-angle glaucoma identified from the Finnish Twin Cohort Study were clinically studied by the author, and 18 other pairs of twins with the disease were ascertained from the Hospital Discharge Registry of Finland. One of the clinically studied pairs was a pair of monozygotic female twins concordant for chronic closed-angle glaucoma and the other was a pair of dizygotic female twins discordant for the disease. Of the pairs of twins ascertained from the registry one was a monozygotic male pair concordant for closed-angle glaucoma. The remaining 17 pairs (12 same-sex dizygotic and 5 monozygotic pairs) were discordant for the disease. The findings support multifactorial inheritance of chronic closed-angle glaucoma. PMID- 3349359 TI - Symptoms and time to presentation and treatment in ocular melanoma: the Western Canada Melanoma Study. AB - Reports on all ocular melanomas newly diagnosed between Apr. 1, 1979, and Mar. 31, 1981, were obtained from the cancer registries of British Columbia, Alberta, Saskatchewan and Manitoba. Of the 90 cases, 87 were in patients aged 20 to 79 years, 64 of whom were interviewed about their initial symptoms. Three symptoms- loss of part of the visual field (in 33% of patients), photopsia (in 20%) and blurred vision (in 20%)--emerged as the main indicators of disease. In 17% of cases the tumour was discovered as an incidental finding on ocular examination. The length of delay before consulting a physician was generally short in symptomatic patients, with 85% reporting that they saw a physician within 3 months of onset of the first symptom. Of the 30 patients who received definitive treatment 4 months or more after initial presentation, 13 were seen by general practitioners who delayed before referring the patient to an ophthalmologist. Continuing medical education is needed to ensure earlier referral to ophthalmologists by general practitioners of patients with ocular melanoma. PMID- 3349362 TI - Diffuse large-cell lymphoma of the nasolacrimal sac. AB - A 63-year-old woman was referred for consultation with a clinical picture of lacrimal sac obstruction. The presence of a noncompressible mass and patency on irrigation suggested a nasolacrimal sac tumour. At biopsy a frozen section was interpreted as being consistent with lymphoma. Examination of permanent histologic sections confirmed the diagnosis of diffuse large-cell lymphoma. Postoperatively, after complete investigation and staging, the isolated extranodal lymphoma was treated with radiation therapy. Non-Hodgkin's lymphoma limited to the lacrimal sac is rare. Its management is discussed. PMID- 3349361 TI - Dural carotid-cavernous sinus vascular malformation with facial nerve paresis. AB - Facial nerve paresis is rarely seen in dural cavernous sinus arteriovenous malformations or carotid-cavernous sinus fistulae. A patient with an otherwise typical presentation of a spontaneous carotid-cavernous sinus malformation was found to have ipsilateral infranuclear facial nerve paresis. Angiography revealed a dural arteriovenous malformation with early petrosal sinus filling. Possible mechanisms for the paresis include compression of the facial nerve by increased venous pressure and "stealing" of the arterial supply by the malformation. PMID- 3349363 TI - Keratometry under anesthesia. PMID- 3349364 TI - Corneal diameter and axial length in congenital glaucoma. PMID- 3349365 TI - Eye injuries in Canadian amateur hockey still a concern [correction]. PMID- 3349366 TI - Preventing transmission of human immunodeficiency virus in ophthalmologic practice. AB - The risk of acquiring HIV infection during an ophthalmologic examination appears to be small but theoretically present. Since it is not always possible to ascertain the presence of HIV infection and because of the grave consequences of infection, all patients must be considered potential carriers. Appropriate preventive measures are imperative. Fortunately, HIV is easily eradicated from the environment. Routine handwashing and cleansing of equipment are normally sufficient to prevent its spread. The fear of AIDS effectively reminds us to adhere to high standards of infection control. This has the added benefit of protecting both physician and patient from other, less lethal but more infective conditions. PMID- 3349368 TI - The psychiatric nurse in a community-based child and youth services setting. PMID- 3349367 TI - Area of visual field and colour discrimination combined as a predictor of chronic open-angle glaucoma. AB - Area of visual field and colour discrimination were assessed in 167 eyes with ocular hypertension (from 100 women and 67 men with a mean age of 59.8 +/- 11.3 years). The patients were then followed for 3 years. During the follow-up period chronic open-angle glaucoma was diagnosed in 8 (8%) of the 100 eyes with a normal visual field and normal colour discrimination, 7 (14%) of the 50 eyes with a subnormal visual field or subnormal colour discrimination, and 17 (100%) of the 17 eyes with both a subnormal visual field and subnormal colour discrimination, a total of 32 eyes (19%). Our results suggest that chronic open-angle glaucoma develops early in ocular hypertensive eyes in which both the visual field and colour discrimination are subnormal. Glaucoma may not develop at all in eyes with normal values. PMID- 3349369 TI - Legal rights and responsibilities of nurses. PMID- 3349370 TI - Percutaneous endoscopic gastrostomy by the "pull" and "introducer" methods. AB - After 28 patients, studied prospectively, underwent percutaneous endoscopic gastrostomy (PEG) by the Ponsky "pull" technique, another 28 patients underwent PEG by the Russell "introducer" method. These two groups were compared retrospectively with 28 patients who had previously undergone Stamm gastrostomy as an independent operation performed by the same group of surgeons. All procedures were done within a 5-year period. The major indication for gastrostomy was the inability to swallow due to neurologic diseases; a similar number of patients in each group also had pharyngeal blockage, cachexia, respiratory failure and inhalation burns. Percutaneous endoscopic gastrostomy could be done most appropriately under local anesthesia, the "introducer" method requiring less time than the "pull" method, which in turn required less time than the Stamm gastrostomy. Feeding was generally instituted successfully 24 hours after PEG compared with 3 days after Stamm gastrostomy. "Introducer" PEG was not associated with peristomal infection, and the authors postulate that the peristomal infections in the "pull" PEG group were due to oropharyngeal bacteria brought through the abdominal wall by that technique. PMID- 3349371 TI - Diagnosis and management of adrenal masses: 1987 Du Pont lecture. AB - Adrenal enlargements were found in slightly more than 100 patients of approximately 15,000 who underwent abdominal computed tomography. A firm diagnosis was made in 61 patients. Of these, 34 were screened because of suspected metastases from nonadrenal tumours. Major causes of adrenal enlargement were metastases (20 patients), nonfunctioning adenomas (15) and hormonally active masses (9). Fine-needle aspiration biopsy was a useful diagnostic aid in patients with metastases. Surgical treatment was undertaken in 17 patients (three pheochromocytomas, one Cushing's adenoma, three Conn's adenomas, four primary carcinomas, two metastatic carcinomas, three nodular hyperplasias suspected to be part of the multiple endocrine adenopathy syndrome and one myelolipoma). Work-up of an adrenal mass includes a full history and physical examination, search for possible nonadrenal primary malignant lesions, testing for excess adrenal hormone secretion, computed tomography of the abdomen and fine-needle aspiration biopsy in selected patients. PMID- 3349372 TI - Gastroplasty with distal gastric bypass: a new and more successful weight loss operation for the morbidly obese. AB - Because of the unacceptable late failure rates associated with other surgical procedures for morbid obesity, the author has performed a new operation-vertical banded gastroplasty with distal gastric bypass-on 70 patients. In seven of these the gastroplasty stoma had to be debanded. The mean lowest loss of excess weight was 88% and the mean final loss of excess weight was 83% for the main group. The postoperative complication rate was acceptable and no late metabolic complications have been seen. This operation gives improved weight loss when compared with gastroplasty or gastric bypass alone and has none of the late complications associated with intestinal bypass. PMID- 3349373 TI - Ileogastrostomy for morbid obesity. AB - Jejunoileal bypass procedures for morbid obesity have been associated with numerous side effects, due mainly to the blind-loop syndrome. To overcome this, the authors describe a new procedure, ileogastrostomy, that they have performed in 50 patients. All had good weight loss and returned to work. Patient satisfaction with the operation was high and self-esteem increased. There were no deaths or severe complications. Stool frequency and foul-smelling stools were still problems but improved with time. Stomal ulceration occurred at 3 months in three patients but resolved within 1 month when treated with H2 blocking agents and was not encountered later than 3 months in any patient. PMID- 3349374 TI - Revision of failed horizontal gastroplasty by vertical banded gastroplasty. AB - Eighteen patients who had undergone horizontal gastroplasty experienced postoperative weight gain due to technical failure (large orifice in 10 patients, staple-line disruption in 7 and a large pouch in 1). A vertical banded gastroplasty was used to correct the problem, with a resulting operative morbidity of 38.9%. This included perforation with peritonitis (five patients) and complete outlet obstruction (two patients). These complications appear to result from poor blood supply to the area of the anastomosis necessary in this conversion. This study indicates that it is not safe to use vertical banded gastroplasty for the failed horizontal gastroplasty. PMID- 3349375 TI - Adverse effect of blood transfusions on patient survival after resection of rectal cancer. AB - Studies have shown that the number of units of blood transfused perioperatively in patients operated on for colonic cancer has a progressively strong negative influence on survival. The present study, involving 198 patients with rectal cancer, was done to determine if perioperative blood transfusions had any prognostic significance. Multivariate regression analysis was applied to these patients, operated for cure of Dukes' stage A, B or C disease. Other variables analysed were age, sex, preoperative hemoglobin, albumin and lymphocyte values and the timing of transfusion. Perioperative deaths, pre- and post-operative immunodepression, neoplasia in situ, nonresections and stage D disease were excluded. It was found that the number of units of blood transfused perioperatively had a negative effect on patient survival, that was independent of the other analysed variables. It is suggested that blood transfusion perioperatively exerts an immunosuppressive effect on patients with rectal cancer. PMID- 3349376 TI - Analysis of a protocol for an autologous blood transfusion program for total joint replacement surgery. AB - This retrospective study analysed an autologous blood transfusion program for total joint replacement surgery. A group of 99 patients receiving autologous blood transfusion was compared with a control group of 55 patients. One-unit phlebotomies were done 14 and 7 days before surgery. The whole blood was transfused intraoperatively. Preoperative hemoglobin values were within the normal range for all patient groups except the female autologous blood group for which the mean value was 122 +/- 11.3 g/L. Due to perioperative hemodilution, the postoperative hemoglobin values were substantially lower than preoperative values for all groups. Mean intraoperative blood loss was similar for the autologous and control groups (650 to 750 ml). No adverse reactions were associated with the autologous transfusions and 74% of the autologous group received autologous blood only. From this analysis a 3-week, three-unit preoperative collection was proposed for future use. A standardized protocol will allow logistical ease and implementation of the program for various surgical procedures. PMID- 3349377 TI - Relationship between deep-vein thrombosis in the calf and fatal pulmonary embolism. AB - Deep-vein thrombosis of the lower limb is common, yet the importance of isolated calf deep-vein thrombosis is poorly understood and the treatment is controversial. This retrospective study documented that 13% of fatal pulmonary emboli originated only from calf deep-vein thrombosis. This rate is similar to that in another study (15%), suggesting that isolated calf deep-vein thromboses do produce fatal pulmonary emboli. PMID- 3349378 TI - Important modification of the jejunoileal bypass procedure for morbid obesity. PMID- 3349379 TI - Prophylactic treatment of stress ulcers: first do no harm. PMID- 3349380 TI - Blood is thicker (and more dangerous) than water. PMID- 3349381 TI - Intimal flaps in manual coronary endarterectomy. PMID- 3349382 TI - 1987 Gallie lecture. Quality control in surgical research: importance to the patient. AB - One of the deficiencies in surgical scholarship is the rarity of timely, well controlled research to evaluate new operative procedures. The invasive aspect of surgery makes randomized studies more difficult to initiate, and in studies with large numbers of participating surgeons, the impact of unsatisfactory surgical expertise (craftsmanship) is a major variable. In an effort to improve surgical research, the use of quality control data for early assessment of the effectiveness of the operative procedure is strongly recommended. Early postoperative studies of stimulated gastric acid secretion have led to improved surgical performance during trials of operations using vagotomy for control of peptic ulcer disease. Similar, early, quality control studies have been effective when investigating selective shunts for control of variceal bleeding; necessary data include shunt patency, portal perfusion of the liver and obliteration of major portoazygous collaterals. Failure to incorporate objective tests for surgical quality control can lead to erroneous assessment of operations. Carefully planned prospective studies of well-performed operations are urgently needed. PMID- 3349383 TI - Injuries to the urethra and urinary bladder associated with fractures of the pelvis. AB - The posterior urethra or urinary bladder may be injured in patients who sustain fractures of the bony pelvis. It is important to assess the urethra radiologically by retrograde urethrography before introducing a urethral catheter to avoid missing a urethral injury or causing further damage. The author's approach to the immediate management of urethral injury is suprapubic cystostomy. The urethra may be repaired later after other injuries have healed. With this approach the incidence of permanent impotence and incontinence will be low and the stricture cure rate high. If the urethra has not been injured, a catheter is introduced and cystography performed to rule out bladder injuries. If the bladder is ruptured, the area is explored, the perivesical space drained and urinary drainage is provided by either a suprapubic cystostomy or a urethral catheter. PMID- 3349384 TI - Hemorrhage and pelvic fractures. AB - Hemorrhage is the major cause of death in pelvic fractures. In closed pelvic fractures the bleeding is usually self-limited. In the small number of patients with continuing hemorrhage there may be disruption of a major iliac vessel, which will require immediate exploration and repair. In a few patients continuing hemorrhage is due to disruption of a branch of the hypogastric artery, which may be identified by angiography and controlled by embolization. A management protocol is suggested for these patients. PMID- 3349385 TI - Infectious problems in pelvic trauma. AB - Pelvic injury provides a challenge to the trauma surgeon. Acute awareness of the possibility of associated hollow-viscus damage must be maintained to identify these injuries and steps must be taken to correct them. This article reviews the current thinking concerning infectious problems in pelvic trauma. With the development of new and more-powerful antibiotics, plus immunomodulators that may correct the suppression of host defences seen after pelvic trauma, there may be an improvement in the number and severity of septic complications that occur following such injuries. PMID- 3349386 TI - The future of general surgery in Canada. AB - Manpower studies carried out by the Canadian Association of General Surgeons revealed a need for approximately 70 new general surgeons to enter practice each year to replace those who will discontinue practice for various reasons. The Royal College of Physicians and Surgeons of Canada certifies about 70 general surgeons each year; however, two-thirds of these pursue further specialty training, leaving only 20 to 25 to continue in general surgery. Training programs in Canada are of variable length and content. Less than half the trainees have substantial research experience. Programs designed to train the comprehensive community general surgeon are lacking in Canadian medical schools and reductions in residency training posts and other governmental constraints may worsen the anticipated shortage of general surgeons. Strong leadership is needed to bring together organized medicine, the surgical specialties, universities and government to address the training and manpower requirements for general surgeons in Canada. PMID- 3349387 TI - Diagnostic value of alkaline phosphatase isoenzyme separation by affinity electrophoresis in the dog. AB - Affinity electrophoresis, using wheat germ lectin, was used to separate the alkaline phosphatase isoenzymes in the sera of 150 dogs with alkaline phosphatase values greater than or equal to 150 IU/L. The method provided clearer separation of the liver, bone and steroid-induced alkaline phosphatase isoenzymes commonly observed in canine serum, compared to conventional cellulose acetate electrophoresis. The dogs were divided into four patient groups determined by previous corticosteroid treatment, evidence of elevated endogenous corticosteroid levels, age and alanine aminotransferase values. The isoenzyme pattern of each patient was qualitatively assessed. The isoenzyme pattern most frequently observed was greater than 50% steroid induced alkaline phosphatase, which was present in 76 of 150 dogs. This pattern was observed in 18 of 22 dogs receiving corticosteroid therapy, two of three dogs with hyperadrenocorticism, and in dogs with a variety of other diagnoses. The majority of immature dogs (12 of 20) had an isoenzyme pattern consisting of greater than 50% bone. The majority of dogs with active hepatocellular injury (16 of 27) had greater than 50% liver isoenzyme. The isoenzyme pattern was not specific for certain diseases, therefore the diagnostic usefulness is limited. However the isoenzyme result is useful in some cases to determine which further diagnostic tests are indicated, and to determine the source of alkaline phosphatase elevation. PMID- 3349388 TI - Healing of cutaneous wounds in the common garter snake (Thamnophis sirtalis). AB - Healing of cutaneous wounds was studied in groups of common garter snakes (Thamnophis sirtalis) held at 13.5 degrees C, 21 degrees C and 30 degrees C. Linear unsutured incisions and circular excisional wounds were evaluated two, five, and ten days after surgery, while linear sutured and unsutured incisions and circular and square excisional wounds were studied three and six weeks after wound production. The sequence of events during healing was the same for all experimental situations. The epithelial margins of the wounds moved freely over exposed epaxial muscle until an exudate of fibrin and inflammatory cells caused adhesion. Heterophils and macrophages were present two days after wounding. Heterophils were present throughout the wound while macrophages were concentrated in areas containing fibrin and proteinaceous exudate. Fibroblasts moved laterally into the wound from the adjacent dermis producing a flat dermal scar oriented parallel to the wound surface. Epithelial cell hypertrophy and hyperplasia occurred in a zone extending up to 1.5 mm from the margin of the wound. A tongue of flattened epithelial cells extended across the wound surface, mingling with the superficial crust and migrating over eosinophilic fibrillar material. Maturation of the new epithelium, indicated by formation of a distinct basal layer, rounding of superficial cells and keratin production, began at the wound margins before the epithelial spurs linked. The epithelium over healed wounds appeared normal, but the dermis did not reorganize to form scales. Reptilian and mammalian healing differ in the character of the inflammatory reaction, the pattern of fibroplasia, and the interaction between epithelial and dermal repair. PMID- 3349390 TI - The effect of ambient temperature and type of wound on healing of cutaneous wounds in the common garter snake (Thamnophis sirtalis). AB - The effects of ambient temperature (13.5 degrees C, 21 degrees C, 30 degrees C) and type of wound on healing of skin wounds were evaluated in common garter snakes (Thamnophis sirtalis). Linear unsutured incisions and circular excisional wounds were evaluated grossly and microscopically in three snakes held at each temperature at each of two, five and ten days after surgery. Linear sutured and unsutured incisions and circular and square excisional wounds were similarly evaluated three and six weeks after wound production in groups of six snakes held at each temperature. The rates of stabilization of wound margins, scab formation, migration and maturation of the regenerating epithelium, resolution of dermal inflammation, and fibroplasia varied directly with temperature. The inflammatory reaction to wounding was similar in character and intensity in snakes held at all three temperatures two days after surgery. Unsutured linear incisions, compared to sutured incisions, tended to have more rapid epithelial maturation and a less intense inflammatory response. Healing of square and circular excisional wounds was similar; contraction of round wounds was slightly more irregular and, at a few observations, dermal maturation was slower and inflammation more widespread. It was concluded that healing of skin wounds can be accelerated by holding reptiles at the upper end of their voluntary temperature range. Wounds, if possible, should be created along the axis of lines of skin tension. Suturing small incisional wounds may not be advantageous. PMID- 3349389 TI - Pharmacokinetics of doxycycline in dogs. AB - Six adult dogs were given doxycycline hyclate at a dosage of 5 mg/kg of body weight intravenously so that pharmacokinetic parameters could be evaluated. Serum doxycycline concentrations were determined over a 48 h period using a modified agar well bioassay. Compartmental pharmacokinetic evaluation of the serum concentration time data indicated that doxycycline has a half-life of 10.36 h, a body clearance of 1.68 +/- 0.44 mL/min/kg, and a volume of distribution at steady state of 1.468 +/- 0.237 L/kg. Doxycycline pharmacokinetics are favorable for therapeutic use in the dog. PMID- 3349391 TI - The effect of certain topical medications on healing of cutaneous wounds in the common garter snake (Thamnophis sirtalis). AB - The effects of four topical medications on the rate and character of healing of cutaneous wounds were studied in six common garter snakes (Thamnophis sirtalis) held at an ambient temperature of 30 degrees C. Two sets of five 6 to 8 mm round excisional wounds, four test and one control site in each set, were created on the dorsolateral body wall of each snake. Wounds were examined daily and treated for ten days, then the snakes were killed and sections of all wounds were examined by light microscopy. Composite scores, derived by ranking each treatment group in relation to the control group (control score = 0) for each of 22 characteristics associated with wound healing, were used to compare the overall effects of each treatment. Statistical comparisons were made between groups for 20 characteristics. Wounds treated with a polyurethane film merited a score of +12 and had significantly more advanced healing than untreated controls for three characteristics. Wounds treated with an ointment containing scarlet red scored +6 but healing was not significantly greater than controls. Wounds treated with an antibacterial spray powder and an antibacterial ointment healed more slowly than controls and had scores of -6 and -12 respectively. PMID- 3349392 TI - The influence of premating feed intake on the reproductive performance of gilts. AB - In an attempt to improve the reproductive performance of gilts mated at puberty, 70 Yorkshire x Landrace gilts were allocated at 120 d of age and 60 kg body weight to one of two treatments. Restricted gilts were fed 2.0 kg d-1 of a diet formulated to provide 18% crude protein and 14.5 MJ DE kg-1 from selection until mated at their first estrus (n = 35). Flushed gilts were fed 2.0 kg d-1 of the same diet from 120 to 150 d of age, but then had their feed intake increased to 3.5 kg d-1 until mated at their first estrus (n = 35). An additional group of gilts (control fed; n = 33) were fed 3.0 kg d-1 from selection until they were bred at their third estrus in order to investigate the influence of feed restriction on the onset of puberty. During gestation all gilts were fed 1.8 to 2.2 kg d-1 of a 16.8% crude protein diet having 13.7 MJ DE kg-1. Control fed gilts were younger (p less than 0.05) at puberty (150 d) than restricted (165 d) or flushed gilts (165 d). There was no difference in subsequent litter size between the restricted and flushed gilts (7.7 and 8.0, respectively). It is concluded that the institution of a flushing nutritional regime in the prepubertal period will not enhance piglet production from gilts mated at puberty. PMID- 3349393 TI - Effects of lesion size and location on equine articular cartilage repair. AB - The mechanisms and completeness of equine articular cartilage repair were studied in ten horses over a nine month period. Large (15 mm square) and small (5 mm square) full-thickness lesions were made in weight bearing and nonweight bearing areas of the radiocarpal, middle carpal and femoropatellar joints. The horses were euthanized in groups of two 1, 2.5, 4, 5 and 9 months later. Gross pathology, microradiography, and histopathology were used to evaluate qualitative aspects of articular repair. Computer assisted microdensitometry of safranin-O stained cartilage sections was used to quantitate cartilage matrix proteoglycan levels. Structural repair had occurred in most small defects at the end of nine months by a combination of matrix flow and extrinsic repair mechanisms. Elaboration of matrix proteoglycans was not complete at this time. Statistically better healing occurred in small weight bearing lesions, compared to large or nonweight bearing lesions. Synovial and perichondrial pannus interfered with healing of osteochondral defects that were adjacent to the cranial rim of the third carpal bone. Clinical and experimental experience suggests that these lesions are unlikely to heal, whereas similar lesions in the radiocarpal and femoropatellar joints had satisfactory outcomes. Observations made in this study support the use of early postoperative ambulation, passive flexion of operated joints, and recuperative periods of up to a year for large cartilage defects. PMID- 3349394 TI - Effect of sample freezing on the isolation of Mycoplasma spp. from the clitoral fossa of the mare. AB - The growth of Mycoplasma equigenitalium and Mycoplasma subdolum from specimens collected from the clitoral fossa of each of four Standardbred mares was not diminished by freezing of the specimens in liquid nitrogen (-196 degrees C) for up to 30 days when compared to samples cultured immediately. PMID- 3349395 TI - Survey of chloramphenicol residues in diseased swine. AB - Tissue samples from 279 hogs suspected of having received antibiotic treatment were collected at federally-inspected abattoirs and submitted for chloramphenicol residue analysis during August and September 1984. Injection sites (when present), kidneys or muscle samples were tested by one of two gas chromatographic methods. Kidney samples were also tested at the abattoirs by the Swab Test On Premises. Thirty-one animals (11%) were found with detectable levels ranging from 1 part per billion to 5727 ppb. Highest levels were found at the injection sites, while levels in muscle tissue did not exceed 500 ppb. None of the kidneys from animals found to contain chloramphenicol residues produced a positive Swab Test On Premises result attributable to the presence of chloramphenicol. Twelve kidneys from animals free of chloramphenicol residues produced positive Swab Test On Premises results. Of these, five contained penicillin or streptomycin, but antibiotic residues were not detected in the remaining seven. In addition to the samples collected for this survey, samples from eight hogs representing a herd which had been treated for pneumonia were submitted by an abattoir in Manitoba in November 1984. Chloramphenicol levels in these animals ranged from 0.1 to 73 parts per million in the injection sites, and from 0.04 to 21 ppm in the muscle tissues. The survey data indicated that there were a significant number of animals reaching the abattoirs with detectable chloramphenicol residues, and that the Swab Test On Premises procedure was ineffective in detecting these animals. PMID- 3349396 TI - Involvement of trauma in the pathogenesis of osteochondritis dissecans in swine. AB - Limb joint soundness was examined in 40 pigs loaded into a wooden box cart and 40 control pigs not subjected to loading. On postmortem examination, eight loaded pigs showed osteochondritis dissecans in their medial humeral condyles, suggesting that porcine joints are vulnerable to osteochondral lesions when mechanically overloaded. Prevention of trauma by careful handling of pigs during penning and transportation should help to control joint lesions and lameness. PMID- 3349397 TI - The prevalence, incidence, geographical distribution, antimicrobial sensitivity patterns and plasmid profiles of milk filter Salmonella isolates from Ontario dairy farms. AB - The prevalence, incidence and geographical distribution of Salmonella on dairy farms in southwestern Ontario were determined by culturing bulk milk filters from 511 randomly selected dairy farms. Milk filters from 22 farms (2.9%) were Salmonella-positive, with a cumulative incidence rate of 9.0% per year. Positive farms were distributed throughout southwestern Ontario, but were regionally clustered. The serotype, biotype, antimicrobial sensitivity pattern and plasmid profile of the Salmonella isolates from six farms where Salmonella were recovered on two occasions were identical. All of the Salmonella strains isolated were sensitive to commonly used antimicrobials. PMID- 3349399 TI - Vaccination of calves with leukotoxic culture supernatant from Pasteurella haemolytica. AB - In three experiments subcutaneous vaccination of calves with adjuvanted bacteria free leukotoxic culture supernatant from log phase cultures of Pasteurella haemolytica A1 (toxin 1) was shown to induce some protection against intrabronchial challenge with live P. haemolytica A1. This toxin 1 vaccine was as effective as a whole cell bacterin in stimulating agglutinating antibody to P. haemolytica. Induction of leukotoxin neutralizing activity was variable; in some cases vaccination only primed the animal to produce an anamnestic response after challenge, whereas in other instances antitoxic activity increased in response to immunization. Two doses of vaccine were shown to be more effective than a single immunization. Vaccination with leukotoxic culture supernatant from the nonpathogenic P. haemolytica serotype 11 was as effective as vaccination with toxin 1 in stimulating antitoxic activity but was not protective. This implies that both serospecific agglutinating activity and an antitoxic response are needed for immunity. PMID- 3349398 TI - Development of turbinate lesions and nasal colonization by Bordetella bronchiseptica and Pasteurella multocida during long-term exposure of healthy pigs to pigs affected by atrophic rhinitis. AB - Natural transmission of atrophic rhinitis from pigs from a herd with an endemic atrophic rhinitis problem to pigs from a herd free of atrophic rhinitis was demonstrated. Six replicates each with five pigs from the endemic atrophic rhinitis herd (Group A) and five pigs from the atrophic rhinitis-free herd (Group B) were housed together from 5 wk of age, with each replicate kept in isolation rooms maintained at optimal and controlled environmental conditions. Three replicates each with six pigs/room from the atrophic rhinitis-free herd (Group C), served as nonexposed controls. Group C pigs remained healthy and had no turbinate atrophy at either 10 or 17 wk of study (atrophic rhinitis score = 0 on a 0 to 3 scale). Group A pigs had a mean atrophic rhinitis score of 1.85 +/- 0.84, and group B pigs developed atrophic rhinitis to a mean score of 1.57 +/- 0.70. The isolation rate and quantity of Pasteurella multocida found on nasal swabs was directly related to lesions while those for Bordetella bronchiseptica were inversely related to turbinate atrophy. Of the various types of P. multocida evaluated, nontoxigenic type A and toxigenic type D were both directly related to atrophic rhinitis while nontoxigenic type D strains were not. No toxigenic type A P. multocida strains were isolated. PMID- 3349400 TI - Serosurvey of Coxiella burnetii infection in dairy goat herds in Ontario. A comparison of two methods of enzyme-linked immunosorbent assay. AB - Two technical variations of enzyme-linked immunosorbent assay for the detection of antibodies to Coxiella burnetii were compared in this serosurvey on 20 Ontario dairy goat herds. Both a trichloracetic acid extract and a coctoantigen of purified coxiellas were used to sensitize the microtitration plates. Technical differences related to coating pH, serum dilutions tested and interpretation of results. Results agreed in 98.6% of sera examined, the differing sera were in the low titer borderline range. Only 20% of the herds had seroreactors. PMID- 3349401 TI - Pharmacokinetics of tetracycline in the domestic rabbit following intravenous or oral administration. AB - Tetracycline hydrochloride was administered to domestic rabbits using a single bolus by the intravenous and oral routes. Pharmacokinetic parameters were determined for intravenous (10 mg/kg) and oral (150 mg/kg) administration. The effect of fasting for 12 h on the drug elimination kinetics after oral administration was evaluated. Tetracycline was added to the drinking water at 800 mg/L or 1600 mg/L. Drug and water intake and serum levels were monitored. Mean serum pharmacokinetic parameters following intravenous administration were; 0 intercept beta curve B (microgram/mL) = 7.5, rate of elimination from body -b (min-1) = 0.0058, half life elimination from body -t 1/2 b (min) = 120.0, wt(kg) = 3.2 determined using combined male and female data. Mean serum pharmacokinetic parameters after oral administration (single bolus) were -B (microgram/mL) = 1.54 (full stomach) and 2.71 (empty stomach), b(min-1) = 0.0037 (full stomach) and 0.0035 (empty stomach), t 1/2 b (min) = 190.3 (full stomach) and 216.2 (empty stomach). Administration of tetracycline in the drinking water produced very low to nondetectable levels of drug in the serum, even at high dosage, and the 1600 mg/L drug concentration was accompanied by a significant drop in water intake. Thus, it is evident that concentrations of tetracycline of up to 1600 mg/L drinking water will not produce levels of antibiotic consistently detectable in the serum. PMID- 3349402 TI - The histological appearance of peroral gastric biopsies in clinically healthy and vomiting dogs. AB - A survey of the histology of gastric biopsies in 501 dogs, consisting of 19 clinically healthy dogs and 482 vomiting dogs is presented. Whole stomachs of four young clinically healthy laboratory dogs were used as controls. Eleven percent of forceps biopsies were unsuitable for examination; all suction biopsies were of good quality. Slight to severe gastritis was found in 168 vomiting dogs (35%), whereas five dogs (26%) of the clinically healthy group showed a mainly slight gastritis. Superficial and diffuse gastritis were the most prominent findings in the 168 dogs with gastritis. A single type of gastritis was found in 114 dogs, a combination of different types in 54 dogs. Gastric atrophy was seen in 23 (5%) vomiting dogs and in three (15%) clinically healthy dogs, atrophy with a slight to severe fibrosis in 21 (4%) vomiting dogs, and in 84 (17%) vomiting dogs and two (11%) healthy dogs, gastric fibrosis was present. Carcinomas were seen in 26 vomiting dogs, of which 17 also had gastritis. A differential diagnosis of granulomatous gastritis/carcinoma had to be made in one case. Seven dogs showed a lymphosarcoma, and in six other dogs a differential diagnosis of lymphosarcoma and/or gastritis was made. One adenomatous polyp was seen. In one clinically healthy dog an adenomyoma was diagnosed. Ulceration was found in 24 dogs, but only five of these lacked other lesions. Other biopsy findings were pseudopyloric metaplasia, hyperplasia, cysts, calcification and edema. Some dogs showed "antralization". PMID- 3349403 TI - The histological appearance of large intestinal biopsies in dogs with clinical signs of large bowel disease. AB - Colonic and rectal forceps and excision biopsies of 355 dogs with clinical signs of large bowel disease were investigated. Five percent of the forceps biopsies were unsuitable for examination; all excision biopsies were of good quality. Forceps biopsies were obtained from one to eight sites, up to 60 cm cranial from the anus, while excision biopsies, mostly from tumors, were from the rectoanal region. Slight to severe colitis and/or proctitis was found in 192 dogs (54%). A single type of colitis was seen in 160 dogs; in 53 cases the lesions were local, in 107 cases multiple. A combination of different types of colitis was found in 32 dogs. Atrophic colitis, diffuse colitis and canine histiocytic ulcerative colitis were the most prominent findings, followed by ulcerative, superficial and eosinophilic colitis. Follicular, hypertrophic and aspecific granulomatous colitis were found in only a few cases. Tumors were diagnosed in 57 dogs (16%). Of these tumors 50 were of epithelial and seven were of mesenchymal origin. A high percentage (61%) of the epithelial tumors consisted of adenomas of the rectoanal region. In ten other dogs (3%) a differential diagnosis of lymphosarcoma or colitis had to be made. Colitis and colorectal tumors were more prevalent in Boxers, German Shepherds, Poodles, Great Danes and Spaniels. In the Boxers simple chronic colitis, as well as canine histiocytic ulcerative colitis were more frequently found, the latter especially in females. Other biopsy findings were edema, crypt cysts, hemorrhages, an increased number of intraepithelial lymphocytes and an increased or decreased number of goblet cells. PMID- 3349404 TI - Porcine focal symmetrical poliomyelomalacia: experimental reproduction with oral doses of encapsulated sodium selenite. AB - Sodium selenite (encapsulated as doses of 1.4 mg, 2.6 mg and 4.2 mg per kilogram of body weight) was given orally on a daily basis to male weaner pigs, and features of these animals were compared to a control group. Porcine focal symmetrical poliomyelomalacia was produced in all experimental groups between 3 and 20 days after initiation of the treatment. Analysis of blood and several tissues revealed an elevated selenium content for all pigs. Histological lesions in the brain and the cervical lumbar/sacral spinal cord enlargements included endothelial proliferation, neuronal degeneration, microcavitation and glial cell reaction. PMID- 3349405 TI - Ultrastructural alterations in the kidneys of Pekin ducks fed methylmercury. AB - Ultrastructural alterations in the kidneys of Pekin ducks were studied after subchronic exposure to methylmercury chloride. Twenty-four male and twenty-four female Pekin ducks, 12 weeks of age were fed 0.0 (control), 0.5, 5.0 and 15.0 parts per million of MeHgCl, mixed in a mash diet for 12 weeks. Birds were observed for clinical signs daily. Kidneys were fixed in situ by perfusion with 4% glutaraldehyde in 0.05 M phosphate buffer and routinely processed for electron microscopy. Only minor morphological changes were observed in the renal corpuscle of ducks in the 0.5 ppm group. The component cells of the renal corpuscle in the 5.0 and 15.0 ppm groups showed several ultrastructural alterations, including an increase in number and size of lysosomes and vacuoles in podocytes and mild vacuolation in mesangial cells. The juxtaglomerular cells of afferent arterioles had crystallized granules. No significant changes were observed in glomerular basement membrane thickness and width of podocyte pedicels. The proximal tubules of the 5.0 and 15.0 ppm groups showed some microvillar loss and an increase in the number and size of lipid droplets, vacuoles and lysosomal bodies. The distal tubular changes in the 5.0 and 15 ppm groups included electron lucency and vacuolation of cytoplasm as well as occasional mitochondrial swelling. The collecting ducts of 5.0 ppm and 15.0 ppm groups showed varying degrees of degenerative changes in both mucus secretory as well as absorptive cells. These results suggest that subchronic exposure of Pekin ducks to methylmercury chloride causes subtle ultrastructural changes in renal corpuscle and marked ultrastructural changes in proximal tubules and collecting ducts. PMID- 3349406 TI - Reference values of blood parameters in beef cattle of different ages and stages of lactation. AB - Reference (normal) values for 12 blood serum components were determined for 48 Shorthorn cows (2-10 years old) and their 48 calves, 357 crossbred cows (12-14 years old), 36 feedlot bulls and 36 feedlot steers. In addition, hemoglobin, hematocrit, triiodothyronine, thyroxine and cortisol levels were determined for the crossbred cows, and feedlot bulls and steers. Reference values were tabulated according to sex, age and stage of lactation. Serum concentrations of urea, total protein and bilirubin, and serum activity of aspartate aminotransferase and lactate dehydrogenase increased with age (P less than 0.05), while calcium, phosphorus and alkaline phosphatase decreased with age (P less than 0.05) from birth to the age of ten years. The Shorthorn cows had the highest levels of glucose at parturition (P less than 0.05) with decreasing levels during lactation. Creatinine concentration decreased during lactation and increased during postweaning. Both lactate dehydrogenase and aspartate aminotransferase levels increased (P less than 0.05) during lactation. Urea and uric acid were present at higher concentrations in lactating than nonlactating cows (P less than 0.05). The values reported, based on a wide age range and large number of cattle, could serve as clinical guides and a basis for further research. PMID- 3349407 TI - Patterns of clinical nurse specialist utilization in United States Hospitals. PMID- 3349408 TI - The critical care clinical nurse specialist: need for hospital and community. PMID- 3349409 TI - The ABCs of external consultation. PMID- 3349410 TI - AFFIRM the role of clinical specialist in private practice. PMID- 3349411 TI - Research priorities. PMID- 3349412 TI - Expert practice of clinical nurse specialists. PMID- 3349413 TI - Content analysis: process and application. PMID- 3349414 TI - National priorities for health care in the future. PMID- 3349415 TI - The gerontological nurse specialist: examination of the role. PMID- 3349416 TI - 5-Fluorouracil, doxorubicin, and cisplatin regimen in adrenal cortical carcinoma. AB - Five patients with metastatic adrenal cortical carcinoma were treated with a combination of 5-fluorouracil (5-FU), doxorubicin, and cisplatin. All patients had a nonhormone producing tumor. A large tumor burden made them unsuitable for mitotane treatment. Treatment could be evaluated in four patients. A complete remission was achieved in one patient and lasted for 38 months: this patient is still alive and free of disease. Furthermore, a minor response and a disease stabilization also were observed. Cardiotoxicity occurred in one patient and myelosuppression in another patient. This regimen appears to be an active combination for the treatment of metastatic adrenal cortical carcinoma. PMID- 3349417 TI - Toxicity following protein A treatment of metastatic breast adenocarcinoma. AB - The toxic effects of protein A (Prosorba, IMRE Corporation, Seattle, WA) treatments given as part of an on-line plasmapheresis or off-line procedure were determined in a Phase I Study. Patients were randomized and treated 12 times either once per week or three times per week with a Prosorba column containing 50 or 200 mg protein A. Treated plasma volumes varied from 150 ml off-line to 2000 ml on-line. Seven patients having advanced metastatic breast adenocarcinoma patients were evaluated. All had advanced progressive disease that was resistant to chemotherapy and/or radiation therapy. Greater than 50% regression of measurable tumor volume occurred in four of seven patients; an additional patient responded with 33.5% regression. Two patients with only bony metastases demonstrated stable disease for a 60-day period. Side effects resulting from protein A treatments included transient fever, chills, rigors, and infrequently nausea, vomiting, diarrhea, episodic hyper and/or hypotension, bronchospasm, venospasm, headache, joint and tumor pain. Mild to moderate reactions were seen in all patients regardless of clinical response, but abated spontaneously or were controlled with pretreatment and/or post treatment with antipyretics and/or antihistaminics. The side effects decreased notably during the course of the week with the more intense reaction occurring during the first treatment of the week. Side effects occurred regardless of column size or volume of plasma treated. In the course of 12 treatments, anemia requiring transfusion developed in two of seven patients. Significant tumor regression was obtained in this group of patients with advanced disease. In light of the mild to moderate side effects and tumor regression in five of seven of the patients treated, protein A treatment merits further evaluation to determine the effectiveness of this treatment in breast adenocarcinoma. PMID- 3349418 TI - Stage II endometrial carcinoma. Results and complications of a combined radiotherapeutic-surgical approach. AB - Since one third of the patients with Stage II endometrial carcinoma have occult extrauterine pelvic metastases at diagnosis, adequate treatment must include the pelvic lymph nodes and parametria. Eighty-three patients with Stage II endometrial carcinoma were treated between January 1964 and December 1983. Sixty nine patients (83%) received combined whole-pelvic irradiation and surgery, five (6%) had surgery alone and nine (11%) had radiotherapy alone. Five-year actuarial survival rates were 67%, 60%, and 38%, respectively. No pelvic recurrence occurred in the 69 patients who received the combined therapy, and there was no vaginal recurrence in the 80 patients treated with intracavity radium. There was a significantly lower incidence of pelvic lymph node metastases (P = 0.03) in patients treated with preoperative irradiation. The median time to recurrence was 17 months, with 67% of the recurrences diagnosed before 2 years, and 88% within 5 years. Ten patients (12%) incurred severe complications and three died as a result. Whole-pelvic irradiation, intracavity radium, and hysterectomy are effective treatment for occult pelvic and vaginal disease. PMID- 3349419 TI - Clinical diagnosis of late temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma. AB - This is a preliminary report of 102 patients with clinical diagnosis of late temporal lobe necrosis after radical radiation therapy for nasopharyngeal carcinoma during 1964 to 1983. Histologic verification was available in 12 cases. All but three patients had been treated in our institute using schedules with doses larger than the conventional 200 cGy per fraction. The incidence rate was 1.03%. In our 80 patients with only one course of external irradiation, the doses to the temporal lobes ranged from 1665 to 2127 ret, or 1286 to 1778 brain tolerance unit (btu). The latent interval ranged from 9 months to 16 years. The median observation period is 33 months. The symptomatology, working diagnosis, treatment, and outcome are described. Surgery was hazardous because of the bilaterality of the involvement and exploration for mere verification of diagnosis was unjustified in typical cases. Treatment with corticosteroid achieved durable objective response in 25 (35%) of 72 patients. The importance of early detection and corticosteroid treatment is discussed. PMID- 3349420 TI - Background mucosal changes in colorectal carcinomas. AB - The entire colonic mucosa of 51 cases of colorectal carcinoma was examined histologically. Mucosal lesions including goblet cell hyperplasia, crypt dilatation, ulceration with regeneration, basal cell hyperplasia, metaplastic lesions, and adenomas were encountered. Goblet cell hyperplasia (80.4%) was most prominent adjacent to the carcinoma (transitional mucosa). Whether this represents a precancerous change is controversial. Crypt dilatation (57%) is considered a nonspecific change due to mucosal injury and indicates obstruction to the outlet of the crypts. Ulceration (6%) is often proximal to the carcinoma and is considered secondary to stasis and ischaemia due to obstruction. Basal cell hyperplasia is particularly prominent at the site of lymphoid follicles. It is suggested that the hyperplasia is a reactive response to the presence of stimuli in the intestinal content. It is observed that metaplastic lesions have their origin from these foci of basal cell hyperplasia. The presence of basal cell hyperplasia in metaplastic polyps (14%) indicates that they are active lesions in the process of formation and growth. The occurrence of metaplastic lesions may provide an indication of an adverse environment and a vulnerable mucosa. Adenomas have their origin from basal cells of colonic crypts. They are present in 47% of colorectal carcinoma. The findings support the view that adenomas are the most common and important precursor lesion associated with colorectal carcinoma in man. No de novo foci of malignant transformation was encountered but this does not exclude the possibility of de novo carcinogenesis of the colorectum. PMID- 3349421 TI - Measurement of tumor cell activity in short-term primary culture. Clinical significance in women with ovarian cancer. AB - In vitro activity was determined by primary culture of tumor samples obtained at surgery from 63 patients with Stage III ovarian cancer. These patients had completed at least 24 months of follow-up. Proliferative activity was measured after 3-hour culture by 3H-thymidine incorporation and metabolic activity by 3H uridine incorporation. A large range of individual tumor activity was found; no correlation was present between proliferative and metabolic activity in the same tumor, the distribution of tumors with high and low activity was similar between histologic types, and the activity was not higher in undifferentiated tumors. There was a strong association between in vitro activity of the tumor and patient outcome (both clinical status and survival). On the basis of in vitro activity, a subset of patients was identified within subgroups with known amount of residual tumor; proliferative activity was a better predictor of good outcome in patients with no residual disease, whereas metabolic activity was better in those with more extensive disease. In these patients, a tumor showing high proliferative and/or metabolic activity (greater than 5000 cpm) was associated with poor survival. PMID- 3349422 TI - DNA flow cytometry applied to fine needle sampling of human breast cancer. AB - Breast cancer cells can be obtained directly from the patient with minimal trauma by fine needle sampling (FNS). A method was developed that enabled us to prepare tumor cell nuclei for ploidy determination by flow cytometry (FCM). Fine needle sampling was performed on 235 patients with clinically suspected malignancy. Two hundred sixteen specimens (92%) produced enough material for assessment; 206 were diagnosed as cytologically malignant. In 41 patients surgical specimens from the same tumors were available. Thirty-eight of these specimens (93%) were classified according to ploidy. No significant correlation was found between aneuploidy and clinical stage (size and lymph node involvement). The comparison of DNA histograms from 21 primary breast tumors and homolateral axillary lymph nodes showed mostly similar patterns. On the contrary, eight of nine synchronous bilateral cancers were shown to have different ploidy. Flow-cytometry-derived DNA histograms of fine needle samples could be a valuable tool in the management of breast cancer. PMID- 3349423 TI - Serial histologic evaluation of multiple primary squamous cell carcinomas of the esophagus. AB - A review of data on 205 patients with esophageal squamous cell carcinoma who underwent subtotal esophagectomy revealed 30 cases (14.6%) and 32 lesions with multiple primary squamous cell carcinomas. The incidence of this multiplicity was 11.7% and 25.6% in those with and without preoperative irradiation treatment, respectively. Among the 32 second lesions, there were 17 intraepithelial carcinomas, eight restricted to the mucosa, five invading the submucosa, one invading down to the proper muscular layer, and one involving the entire thickness of the esophageal wall. These second lesions were in the relatively early stage. Moreover, incidence of the coexistence of intraepithelial carcinoma contiguous to the main lesion was 42.1% and 100.0% in those with multiple cancers, with and without preoperative irradiation, respectively. The values were 7.6% and 53.1% in patients with a solitary carcinoma, respectively. These findings show the close relationship between multiplicity and intraepithelial carcinoma contiguous to the main lesion, and support the concept of multicentric or field carcinogenesis of esophageal squamous cell carcinoma. PMID- 3349424 TI - Renal cell carcinoma. Prognostic significance of morphologic parameters in 121 cases. AB - Morphologic parameters were correlated with survival in 121 renal cortical neoplasms including 116 carcinomas and five oncocytomas. An increasing nuclear grade was generally correlated with a significant decrease in disease-free survival although no statistical difference was found between nuclear Grade 1 and 2 tumors. Similarly, a higher stage at diagnosis predicted a shorter disease-free survival. Renal vein invasion adversely affected prognosis only for high nuclear grade carcinomas. Papillary and spindled carcinomas, independent of nuclear grade, were associated with a significant decrease in disease-free survival compared to tumors with a solid pattern. Patients with large neoplasms (greater than 10 cm) had a significantly worse disease-free survival than patients with tumors 10 cm or less. The prognostic significance of tumor cell type is less clear. Patients with oncocytomas had the best disease-free survival compared with patients with tumors of other cell types. However, the difference in survival was not statistically significant for low-grade tumors, suggesting that nuclear grade rather than cell type may be the more important determinant. PMID- 3349425 TI - Melanocytic atypia in dysplastic nevi. Immunohistochemical and cytophotometrical analysis. AB - In a double-blind study a correlation was found between the histologically assessed degree of nevomelanocytic atypia in 58 dysplastic nevi (DN) and the presence of two markers associated with malignant transformation. The markers included a marked expression of histocompatibility locus Class I antigens on nevomelanocytes (P less than 0.01) and abnormalities in the nuclear DNA content as measured by DNA cytophotometry (P = 0.01). Both markers were present in most of the markedly atypical DN, in about half of the moderately atypical DN, and in less than 30% of the mildly atypical DN. These findings suggest that a DN with marked or moderate melanocytic atypia indicates a premalignant condition and identifies a patient at risk for melanoma. PMID- 3349426 TI - Malignant lymphoma arising in a large congenital neurofibroma of the head and neck. Report of a case. AB - A lymphoma developed in a large neurofibroma in a young woman who had no other stigmata of neurofibromatosis. The neurofibroma was congenital and extensively involved the soft tissue and bone of the face and neck. Despite multiple attempts to excise the neurofibroma, it persistently recurred. At the age of 30 the patient underwent another resection of the lesion, and a follicular, mixed, small and large cell lymphoma was present within the neurofibroma. Over 3 years the lymphoma transformed into a diffuse large cell type despite the fact that it remained localized to the neurofibroma. After the lymphoma had transformed, the patient received multiagent chemotherapy. She responded well, and a repeat biopsy showed no residual lymphoma. She is alive and well 25 months after completion of chemotherapy. To the best of our knowledge, this is the first report of a lymphoma arising in a soft tissue neoplasm. PMID- 3349427 TI - Iodide-induced thyrotoxicosis in a thyroidectomized patient with metastatic thyroid carcinoma. AB - An unusual case of iodide-induced thyrotoxicosis is documented in this article. The patient was a 64-year-old euthyroid man with acromegaly. He also had multiple follicular and papillary thyroid carcinomas with a metastatic lesion in the lumbar vertebrae. After a total thyroidectomy, he became slightly hypothyroid, and the lumbar lesion began to incorporate 131I by scintigraphy. When an iodine containing contrast medium happened to be injected, a transient increase of serum thyroid hormone level was observed. After complete thyroid ablation with 83 mCi of 131I, the oral administration of 100 mg of potassium iodide for 7 days induced a prominent increase of serum thyroid hormone level. These findings indicated that the metastatic thyroid carcinoma could produce excess thyroid hormone insofar as a sufficient amount of iodide was given. Although this is the first report of such a case, iodide-induced thyrotoxicosis may not be rare in patients with thyroid carcinomas because the Wolff-Chaikoff effect is thought to be lost, and the organic iodinating activity and lysosomal protease activity are well preserved. PMID- 3349428 TI - Epidemiology of carcinoma in situ of the upper aerodigestive tract. AB - Epidemiologic analyses of upper aerodigestive tract (UAT) carcinoma in situ (CIS) are nonexistent, hence only hospital records and surgical pathology resources are available for its descriptive characterization. The National Cancer Institute's Surveillance, Epidemiology and End Results investigation has, however, published valuable raw data pertaining to CIS of the UAT. This information is analyzed here and summarized for the first time, demonstrating the following: a male incidence rate which is four times greater than the female rate (0.8/100,000 males versus 0.2/100,000 females); similar ages at diagnosis for both sexes (62.7 and 60.0 years of age for males and females, respectively); no significant urban/rural incidence differences; that CIS represents 2.8% of all UAT malignancies; that 2.0% of all CIS lesions in humans are found at UAT sites; and that CIS of the uterine cervix is not a good model for CIS of the UAT. PMID- 3349429 TI - Carcinoma in situ of the upper aerodigestive tract. Incidence, time trends, and follow-up in Rochester, Minnesota, 1935-1984. AB - Epidemiologic analyses of carcinoma in situ (CIS) of the upper aerodigestive tract (UAT) are virtually nonexistent. The current investigation summarizes the total UAT CIS experience of a white, middle class community from 1935 through 1984. Average annual incidence rates varied between genders (3.1 per 100,000 person-years for males versus 0.6 per 100,000 person-years for females), and increased from 1.5 to 3.1 lesions per 100,000 person-years between 1935 and 1964, and 1965 and 1984. Virgin CIS lesions represented 13% of all UAT carcinomas and the vermilion borders of the lips accounted for 42% of all UAT CIS cases. Age specific incidence rates for males demonstrated a continuous increase with increasing age to 40.5 per 100,000 for males older than 75 years. A clinicopathologic analysis of these lesions is provided. PMID- 3349430 TI - Results of laparotomy in immunoproliferative small intestinal disease. AB - Immunoproliferative small intestinal diseases (IPSID), previously known as Mediterranean Lymphomas, constitute more than 60% of the non-Burkitt's small intestinal lymphomas in Tunisia. A multidisciplinary study of IPSID was undertaken by the Tunisian/French Lymphoma Study Group in 1980 to reach a better understanding of the two subgroups of the disease: secreting IPSID (essentially alpha-chain disease [ACD]); and nonsecreting IPSID (NS-IPSID) (extensive small intestinal lymphomas without gammopathy). The results of initial exploratory laparotomy performed in 38 cases of IPSID (17 ACD and 21 NS-IPSID) are described here, and show notable similarities between the two groups: the extensive pattern of the abnormal cell infiltrate along the major part of the small intestine; frequent and extensive involvement of the mesenteric lymph nodes; the existence of several degrees of severity in small intestinal mesenteric lymph nodes; and other intraabdominal organ involvement. Certain differences also were observed: the relatively high degree of tropism of the NS-IPSID towards the gastric mucosa which was absent in the ACD of this series; and the more frequent involvement of the entire length of the small bowel in ACD. In spite of these discrete differences, the IPSID form a homogeneous group which is definitely distinguishable from the segmentary small intestinal lymphomas known as Western type, and which account for approximately one third of our non-Burkitt's small bowel lymphomas. PMID- 3349431 TI - Solitary plasmacytoma of the spine. Long-term clinical course. AB - The data for 19 patients with solitary plasmacytoma of the spine were reviewed with regard to clinical course and prognosis (median follow-up, 96 months). Eight patients presented with spinal cord compression. A monoclonal immunoglobulin was initially detected in seven of 15 evaluable patients. Treatment included radiotherapy (18 of 19) and/or surgery (11 of 19) and chemotherapy (eight of 19). Spinal cord compression was reversed in every patient. The expected survival rate was 85% at 10 years after diagnosis. Local recurrence or dissemination was observed in 13 patients. It occurred within 5 years of diagnosis in 11 patients and was localized (that is, local recurrence or single bone metastasis) in eight patients. It was always associated with the appearance or an increase of the M component. Dissemination frequently had a "metastatic" pattern with no diffuse bone marrow plasmacytosis. The incidence of local recurrence (five patients) and leukemia (four patients) was high. Local recurrence and/or dissemination were significantly more frequent in patients with the M component at diagnosis than in those without it (P less than 0.05; relative risk, R = 4). The effectiveness of surgery and chemotherapy combined with radiotherapy is also discussed. PMID- 3349433 TI - Dormant dangers of DES. PMID- 3349432 TI - Tumor burden as the most important prognostic factor in early stage Hodgkin's disease. Relations to other prognostic factors and implications for choice of treatment. AB - Two hundred ninety patients with Hodgkin's disease pathologic stage (PS) I or II were treated in the prospective randomized trial of the Danish National Hodgkin Study (see Appendix) with radiotherapy +/- adjuvant combination chemotherapy. The initial tumor burden of each patient was assessed, combining tumor size of each involved region and number of regions involved. Multivariate analyses of prognostic factors including treatment, tumor burden, histologic subtype, pathologic stage, number of involved regions, mediastinal size, systemic symptoms, erythrocyte sedimentation rate (ESR), sex, and age were carried out. With regard to disease-free survival tumor burden was by far the most important prognostic factor for patients treated with adjuvant chemotherapy as well as for patients treated with radiotherapy alone. With regard to survival from Hodgkin's disease only tumor burden and age were independently significant. A combination of tumor burden, histologic subtype, and sex singled out patients with a high relapse rate both after radiotherapy only, and after radiotherapy plus chemotherapy. This combination also singled out patients destined to die from Hodgkin's disease more accurately than other prognostic factors. PMID- 3349435 TI - [Death and its place in our life]. PMID- 3349434 TI - Branded for life? PMID- 3349436 TI - [Information systems--advantages and installation]. PMID- 3349437 TI - Sister chromatid exchange and cell cycle patterns of normal human bone marrow cells after in vitro exposure to cytostatic drugs. AB - The effect of different cytostatic chemotherapeutic drugs on the frequency of sister chromatid exchanges and growth kinetics of the bone marrow cells in normal adults was studied by means of an in vitro bromodeoxyuridine chromosome labeling method. Cytosine arabinoside, harringtonine, methotrexate, vincristine, and 6 mercaptopurine were tested. Three of these agents induced significantly high frequency of sister chromatid exchange (p less than 0.01 or p less than 0.05). The sister chromatid exchange frequency induced by cytosine arabinoside and that induced by 6-mercaptopurine were higher than those of the control group. The increased frequency of sister chromatid exchange predominated in C and A group chromosomes. At the concentration adopted by the authors, the growth kinetics were little influenced by these drugs. PMID- 3349438 TI - Immunoglobulin allotypes Gm and Km in hematologic malignancies. AB - Immunoglobulin allotypes of the Gm and Km systems have been compared in patients with various forms of hematologic malignancies and healthy controls of the same ethnographic background. These comparisons found an increased frequency of the haplotype Gm and a decreased frequency of Gm in patients with Hodgkin's disease; a decreased frequency of Gm in diffuse, large-cell lymphoma patients; a decreased frequency of Gm and an increased frequency of Gm in acute myeloid leukemia patients; a decreased frequency of Gm in chronic myeloid leukemia patients, and an increased frequency of the phenotype Km(1+) in chronic lymphocytic leukemia patients. These results support previous suggestions of the involvement of immunoglobulin allotypes in the susceptibility to some forms of human hematologic malignancy. PMID- 3349439 TI - Binucleated cells in a human renal cell carcinoma with 34 chromosomes. AB - Cytogenetic analysis of a human renal cell carcinoma revealed a near-haploid chromosome number of 34 with the loss of one chromosome #1, #2, #3, #6, #7, #9, #10, #12, #13, #17, #18, and #21. Binucleated cells were observed in histologic, cytologic, as well as in cytogenetic preparations. The paper briefly discusses the binucleation-polyploidization as a possible compensatory mechanism to maintain the genetic balance in near-haploid cells. PMID- 3349440 TI - Consistent involvement of band 12q14 in two different translocations in three lipomas from the same patient. AB - We studied cytogenetically three distinct lipomas from a patient with multiple subcutaneous lipomas in the left shoulder area. A breakpoint at 12q14 was involved in structural rearrangements in the three lipomas resulting in two different reciprocal translocations, i.e., t(3;12)(q28;q14) in two and a t(1;12)(q34.2;q14) in the third. These results confirm the consistency of involvement of the breakpoint at 12q14 in lipomas and give support to the hypothesis that multiple lipomas evolve from different stem cells. PMID- 3349441 TI - Effect of differentiating agents on nucleolar organizer region activity in human melanoma cells. AB - A human cell line established from a metastatic melanoma had both multiple numerical and structural chromosome aberrations including one to two copies of a submetacentric marker chromosome with an insertion of an active nucleolar organizer region (NOR). Treatment of this cell line with retinoic acid (RA) induced morphologic differentiation and reduced the cellular saturation density concomitant with a significant decrease in Ag-NOR activity. RA-treated cells grown in the absence of this differentiating agent, however, displayed a return to normal Ag-NOR activity, indicating the effect of this chemical on ribosomal genes is reversible. PMID- 3349442 TI - Rhabdomyosarcoma in Roberts syndrome. AB - A 23-month-old child diagnosed as having Roberts syndrome, born to consanguineous parents, developed a sarcoma botryoides. Cytogenetic evaluation of peripheral blood lymphocytes and tumor cells showed premature centromere separation, which is characteristic of Roberts syndrome. PMID- 3349443 TI - The molecular cytogenetics of colon cancer. PMID- 3349444 TI - Do clonal chromosome abnormalities prognosticate early relapse in Hodgkin's disease? PMID- 3349445 TI - Dietary restriction, cell proliferation and carcinogenesis: a preliminary study. AB - Four groups of female Swiss Webster mice were given either laboratory chow or a purified (semi-synthetic) diet (AIN-76A) either ad libitum or at 75% of the ad libitum rate for about 30 days. Three tissues, the crypt cells of the jejunum, the dermis and the basal epithelial cells of the esophagus were investigated using [3H]thymidine labelling and by counting mitoses; four other tissues, the alveolar cells of the mammary gland, the crypt cells of the duodenum and colo rectum, and the transitional cells of the urinary bladder were examined using [3H]thymidine labelling only. In each case dietary restriction led to a reduction of cellular proliferation assessed by these indices. The potential of the approach for the study of the effects of dietary modification on the induction of cancer is discussed. PMID- 3349446 TI - Observations on the chemical structure and cytotoxic activity of marycin, a hematoporphyrin derivative. AB - This paper describes the preparation, chemical structure and cytotoxic activity of marycin, a hematoporphyrin derivative. Marycin has been prepared by condensing hematoporphyrin dimethyl ester in the presence of p-toluenesulfonic acid and reducing the product with lithium aluminum hydride. The product appeared to be pure by thin-layer chromatography (TLC) and high-performance liquid chormatography (HPLC). The product, analyzed by UV-visible absorbance and fluorescence spectra, appears to be related to the parent hematoporphyrin compound. The product was also analyzed by NMR and Mass spectra: a dimeric structure can be assigned to marycin: this appears to have an oxide bridge between C2-chains of two porphyrin units and hydroxyl groups instead of carboxyls. Marycin was screened for cytotoxic activity against ZR-75, MCF-7, HT 29, K-562, human tumor cell lines and the MRC-9 human embryonic cell line. Marycin decreases the growth index, measured in the radiometric assay, as 14CO2 production. The cytotoxic activity was dose-dependent and is attributable to the pure compound, marycin. Marycin is active at low doses but the activity varies with the cell line studied. The compound had low toxicity versus MRC-9 normal cell line. The compound is active without light activation. How marycin acts is a matter of speculation. Marycin is highly liposoluble and would be expected to have high toxicity for tumors. PMID- 3349447 TI - Occurrence of volatile N-nitrosamines in dried chillies. AB - Twenty samples of dried chillies, fresh chillies and chilli sauces have been analysed for the presence of volatile N-nitrosamines. Over 75% of both dried whole chillies and chilli powder samples analysed contained N nitrosodimethylamine and N-nitrosopyrrolidine (NPYR) at concentrations of 0.66 16.5 micrograms/kg and 0.48-6.0 micrograms/kg, respectively. Fresh chillies and chilli sauces were not found to contain volatile N-nitrosamines. PMID- 3349448 TI - Assessment of L-ascorbic acid requirement for prolonged survival in ODS rats and their susceptibility to urinary bladder carcinogenesis by N-butyl-N-(4 hydroxybutyl)nitrosamine. AB - Assessment of L-ascorbic acid requirement for prolonged survival in ODS (genotype: od/od) rats and their susceptibility to urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) were examined. In ODS rats without L-ascorbic acid synthesizing ability, the 50 ppm dietary total ascorbic acid (TAA) was insufficient to survive for 4 weeks, the 250 ppm dietary TAA was sufficient to survive for 36 weeks. In examination of BBN treatment, ODS rats- although showing a lower availability of TAA than the heterozygotes (+/od) and normal (+/+) rats with L-ascorbic acid synthesizing ability--were equally susceptible to bladder carcinogenesis. PMID- 3349449 TI - Elevated DNA polymerase beta activity in a cis-diamminedichloroplatinum(II) resistant P388 murine leukemia cell line. AB - The activity of DNA polymerase beta, which is an enzyme involved in repair of DNA damage, was assessed in P388 murine leukemia cell lines sensitive and resistant to cis-diamminedichloroplatinum(II) (cis-Pt). The resistant line was selected with cis-Pt and showed cross-resistance to a number of alkylating agents, but not to an anthracycline. The DNA polymerase beta activity was found to be elevated 5 fold in the resistant line based upon activity per mg cell protein and elevated 4 fold based upon activity per 10(7) cells. The characterization of elevated activity of an enzyme active in DNA repair in a cell line resistant to DNA damaging agents describes a possible mechanism of resistance in addition to those previously found. PMID- 3349450 TI - Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer. AB - Rectal biopsies and fecal collections were obtained from a consecutive series of 34 outpatients prior to colonoscopy at a gastroenterology clinic. Subsequently, 14 were found to have no colonic pathology, 13 had adenomatous polyps, (3 of those had a previous history of colon cancer) and 7 were diagnosed with colon cancer. In confirmation of earlier studies the tritiated thymidine labelling index was higher in patients with tumors than in those without pathology (7.9% vs. 5.8% with P = 0.06). The patients with colonic tumors also had significantly higher levels of deoxycholic acid (P = 0.01) and lithocholic acid (P = 0.005) in the aqueous extract of their feces. This study shows that these biochemical measures may indicate colon cancer risk. PMID- 3349451 TI - N-nitrosoephedrine and N-nitrosopseudoephedrine: their dissolution, absorption, blood clearance and elimination studies. AB - Dissolution and absorption rates (in vitro); clearance from blood and elimination rates of N-nitrosoephedrine (NEP) and N-nitrosopseudophedrine (NPEP) in mice were determined. The two isomers obeyed first-order kinetics and from the slope of the regression line, the rate constant for each study was obtained. These constants were 0.023, 0.038 min-1 (dissolution); 0.192, 0.225 h-1 (stomach absorption); 2.898, 1.980 h-1 (intestinal absorption); 0.33, 0.55 h-1 (blood clearance) and 0.373, 0.393 h-1 (elimination from whole animal) of NEP and NPEP, respectively, and were tested by Student's t-test. Significant differences in the dissolution, absorption and blood clearance rates of NPEP from those of NEP have been observed (P less than 0.05-0.01). These differences are expected to exert their influence on the metabolic rates and the carcinogenic and/or spectral properties of NEP and NPEP, in a related pattern. PMID- 3349452 TI - Growth of Sinclair swine melanoma as a function of age, histopathological staging, and gonadal status. AB - We have analyzed the association between host hormonal status and growth rate of congenital exophytic melanomas of Sinclair swine. The growth of multiple exophytic lesions during the first year of life of intact males, orchiectomized males, intact females, and ovariectomized females was quantitated using a proliferative index which assigned a numerical value to fixed increments of gains or losses in tumor volume. The proliferative index from 6 wk (gonadectomy at 6 wk) to 52 wk of age of each treatment group was statistically increased from 0 (P less than 0.01) except that of gonadectomized females. The proliferative indices from lesions in gonadectomized females were significantly lower than those from intact males, intact females, and gonadectomized males. A total of 93 exophytic tumors from 63 swine were biopsied and histopathologically staged according to the degree of progression or regression and analyzed as a function of animal age. There were no Stage I and only two Stage II lesions at the time biopsies were taken. Twenty-six of 32 (81.2%) Stage III tumors were found in swine of both sexes less than 26 wk of age of which 71.8% were found less than 10 wk of age, while 20 of 29 (68.9%) were Stage IV, and only 3 of 32 (9%) were Stage V lesions present in this age group (P less than 0.001, chi 2). Only 20.7% of Stage IV tumors were present prior to 6 wk of age. Preliminary results suggest that castration of either sex also altered tumor histopathology. Our data suggest that a reduction in gonadal steroid secretion was associated with a decrease in exophytic tumor growth rate and regression in animals of both sexes during the first year of life in Sinclair swine. The effect in female swine was due to significant reduction in the proliferative index over the first 6 mo of age. PMID- 3349453 TI - Pathobiological effects of acrolein in cultured human bronchial epithelial cells. AB - The ability of the highly reactive aldehyde acrolein to affect growth, membrane integrity, differentiation, and thiol status and to cause DNA damage has been studied at serum- and thiol-free conditions using cultured human bronchial epithelial cells. Acrolein markedly decreases colony survival at 3 microM whereas about 10-fold higher concentrations are required to increase membrane permeability, measured as uptake of trypan blue dye. Acrolein at micromolar concentrations also causes epithelial cells to undergo squamous differentiation as indicated by decreased clonal growth rate, dose-dependent increased formation of cross-linked envelopes, and increased cell planar surface area. Acrolein causes a marked and dose-dependent cellular depletion of total and specific free low-molecular-weight thiols as well as protein thiols. Exposure to acrolein did not cause oxidation of glutathione indicating that thiol depletion occurred by direct conjugation of reduced glutathione to acrolein without concomitant generation of active oxygen species. Furthermore, acrolein is genotoxic and causes both DNA single strand breaks and DNA protein cross-links in human bronchial epithelial cells. The results indicate that acrolein causes several cytopathic effects that relate to multistage carcinogenesis in the human bronchial epithelium. PMID- 3349454 TI - Neosynthesis of neolacto- and novel ganglio-series gangliosides in a rat fibroblastic cell line brought about by transfection with the v-fes oncogene containing Gardner-Arnstein strain feline sarcoma virus-DNA. AB - Transfection of retrovirus DNA from Gardner-Arnstein strain feline sarcoma virus containing v-fes oncogene into a rat fibroblastic cell line 3Y1 caused not only cell transformation but also a remarkable change in ganglioside expression. The ganglioside phenotype of the 3Y1 cells was characterized by the exclusive expression of GM3, along with a trace amount of "A" pathway-related gangliosides (GM2-GM1a-GD1a), whereas in the transfected transformant, 3Y1-GA, sialosylparagloboside containing N-acetyl neuraminic acid (NeuAc) and novel ganglio-series gangliosides (presumably GM1b and GD1 alpha) were expressed in addition to GM3. Thus, the Gardner-Arnstein strain feline sarcoma virus DNA transfection open two new ganglioside metabolic pathways, one leading to the synthesis of neolacto-series and the other to that of ganglio-series gangliosides. These results were in striking contrast to the cases of transfection with so-called "intranuclearly expressed" transforming genes, adenovirus E1, SV40-T, and myc, with which the same 3Y1 cells newly expressed GD3 with a concomitant decrease in precursor ganglioside GM3. The difference in underlying mechanisms of ganglioside metabolism shown by these two different types of oncogenes might reflect differences in the modes of action of the oncogenes and their biological activities. PMID- 3349455 TI - Phorbol ester-induced G2 delay in HeLa cells analyzed by time lapse photography. AB - The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown previously to mimic X-irradiation in altering cell cycle parameters in Hela cells [Kinzel, V., Richards, J., and Stohr, M., Science (Wash. DC), 210: 429-431, 1980]. These changes include a delay in G2 phase from which cells recover in the presence of TPA, which suggests an involvement of cellular mediators. In order to obtain information on the onset and the duration of the G2 delay, as well as the onset and rate of recovery, a time-lapse study has been carried out. The analysis of cells in prophase shows that at 10(-6) M and 10(-7) M concentrations, TPA and 12-O-retinoylphorbol-13-acetate (RPA) cause a G2 delay which lasts on the order of 3.5 to 4 h. Below 10(-7) M of RPA and below 10(-8) M of TPA a clear-cut inhibition of HeLa cells in G2 is no longer detectable by this method. These results for a given phorbol ester are dose dependent within a certain range but unlike the case of X-rays are not proportional to dose. Within the dose range studied the recovery rate follows the opposite order. At 10(-6) M TPA and RPA an indication of a parasynchronous burst is observed. At smaller concentrations or with less biological activity of phorbol ester, the cell multiplication rate approaches that of the control or remains even smaller. Possible reasons are discussed. The determination of the transition points seems to indicate that the cellular events inhibited in G2 occur shortly before visible prophase. PMID- 3349456 TI - Structural requirements for stimulation of colonic cell proliferation by oxidized fatty acids. AB - The primary autoxidation products of polyunsaturated fatty acids are known to stimulate DNA synthesis and induce ornithine decarboxylase activity in colonic mucosa. In the present study we have determined the structural features of the oxidized fatty acids necessary for the stimulation of these two components of mitogenesis. Compounds were instilled intrarectally in either aqueous or mineral oil vehicles and 3 h later (ornithine decarboxylase activity) or 12 h later (tritiated thymidine incorporation), the animals were killed and the colonic mucosa harvested for measurement of the two parameters of cell proliferation. Hydroperoxy and hydroxy fatty acids derived from oleate and stearate were studied. Ricinoleic acid and the alpha,beta-unsaturated ketone derived from oleic acid were also investigated. The minimal requirement for stimulation of cell proliferation is the presence of an oxidized functionally adjacent to a carbon carbon double bond. All active compounds studied were roughly equipotent, which suggests a common mediator may be involved. These results imply that, in addition to biliary steroids, the autoxidation products of unsaturated fatty acids may play a role in the enhancement of tumorigenesis by high levels of dietary fat. Furthermore, the data suggest a possible mechanism of action for the active compounds. PMID- 3349457 TI - Effect of dietary excess of inorganic selenium during initiation and postinitiation phases of colon carcinogenesis in F344 rats. AB - The effect of supplemental inorganic selenium given during the initiation or postinitiation phase of colon carcinogenesis induced by azoxymethane [(AOM)CAS:25843-45-2] was studied in male F344 rats. Weanling animals were raised on AIN-76A semipurified (control) diet. Starting at 4 wk of age, groups of animals intended for initiation study were fed the semipurified diets containing 0.5 and 2.5 ppm selenium in the form of sodium selenite, and those intended for postinitiation study were continued on the control diet. At 7 wk of age, all animals except the vehicle-treated controls were injected s.c. with AOM (15 mg/kg body weight, once weekly for 2 wk). One wk following AOM treatment, animals in the initiation study receiving the supplemental selenium were transferred to the control diet whereas those in the postinitiation study receiving the control diet were transferred to the diets containing 0.5 and 2.5 ppm selenium. These animals were continued on this regimen until the termination of the experiment at 34 wk post-AOM injection. Tissue and blood glutathione peroxidase activity was measured in vehicle-treated animals fed the control and selenium-supplemented diets. The results indicate that body weights were comparable among the various dietary groups. Feeding of diets containing 0.5 and 2.5 ppm selenium during the initiation phase had no effect on colon tumor incidence, but the multiplicity of adenomas was slightly inhibited in animals fed the 2.5 ppm selenium diet. The incidence and multiplicity of colon adenocarcinomas and the multiplicity of colon adenomas were inhibited in animals fed the 2.5-ppm selenium diet during the postinitiation phase of carcinogenesis. The incidence of small intestinal tumors was higher in animals fed the 2.5-ppm selenium diet during the initiation phase than in animals fed the control diet and 0.5-ppm selenium diet. Selenium dependent glutathione peroxidase activity was increased in kidneys and small and large intestinal mucosae of animals fed the 2.5-ppm selenium diet compared to those fed the 0.5-ppm selenium and control diets. PMID- 3349458 TI - In vitro antiproliferative activity of combinations of ether lipid analogues and DNA-interactive agents against human tumor cells. AB - Ether lipid analogues of platelet-activating factor (1-octadecyl-2-acetyl-sn glycero-3-phosphocholine) possess a wide range of biological activities, including inhibition of neoplastic cell growth in vitro and in vivo. This activity is believed to be membrane mediated. Three different ether lipid analogues, 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine, 1-thiohexadecyl-2 ethyl-rac-glycero-3-phosphocholine, and 4-amino-methyl-1-[2,3-(di-n-decyloxy)-n propyl]-4-phenylpiperidine , were combined with three DNA-interactive drugs, Adriamycin, 4-hydroperoxycyclophosphamide, and cisplatin, in the expectation that combinations of drugs with different mechanisms of action might show enhanced antitumor activity. The in vitro antiproliferative activity of the combinations was measured with a semisoft agarose clonogenic assay of an ovarian adenocarcinoma cell line. Various permutations of drug combinations were studied. Isobologram analyses and different treatment schedules were performed. Enhanced antiproliferative activity was found with combinations of ether lipids with DNA interactive drugs in comparison with single agents. Statistical evaluation of the data indicated that the increase in activity was due to an additivity phenomenon. Neither synergism nor antagonism was found. PMID- 3349459 TI - Isolation and initial characterization of thermoresistant RIF tumor cell strains. AB - Heat-resistant cell strains were obtained from RIF-1 mouse tumor cells by repeated heatings of cells derived from survivors of previous heating cycles (60 min; 45 degrees C). Twenty thermally resistant (TR) strains were derived from single cells that had survived 11 heating and regrowth cycles. These were then analyzed for appropriate characteristics in vitro and in vivo. In vitro we looked for: marked heat resistance; high plating efficiency; growth rate similar to that of RIF-1 cells; and no obvious morphological abnormalities. In syngeneic hosts, we looked for: ability of the cells to form tumors whose growth rates were similar to that of RIF-1 tumors; high cellular heat resistance; good plating efficiency of tumor-derived cells; and low immunogenicity. Five strains having these desired characteristics were analyzed for survival kinetics. The heat resistant phenotype was found to be stable in vitro, although partial reversion in vivo was seen occasionally. The "break" in the Arrhenius plot was found to occur at 45 degrees C in TR strains versus 43 degrees C in RIF-1. All TR strains and the RIF-1 line developed similar levels of thermotolerance (as defined by slope ratios) when given isosurvival heat exposures. X-ray responses of TR and RIF-1 cells were indistinguishable both with respect to survival and to heat induced radiosensitization. While the number of live cells required to give tumor takes in 50% of the recipients for TR strains was appreciably higher than that for RIF-1 cells, radiation-killed cells from none of the strains were able to immunize efficiently against subsequent challenges by live cells. PMID- 3349460 TI - Comparison of tumor targeting of mouse monoclonal and goat polyclonal antibodies to carcinoembryonic antigen in the GW-39 human tumor-hamster host model. AB - We have evaluated 4 radioiodinated mouse monoclonal anticarcinoembryonic antigen antibodies (MAbs) by using the GW-39 human colorectal tumor xenograft transplanted i.m. in immunocompetent hamsters to determine whether there were any differences in their tumor localization properties. Additional comparisons were made to affinity-purified goat anticarcinoembryonic antigen antibody. Statistically significant differences were found in the percentage/g of tumor uptake and tumor/nontumor ratios among the antibodies, so that the antibodies could be ranked according to their tumor localization properties (NP-2 greater than NP-4 = goat antibody greater than NP-1 greater than NP-3). Although statistical differences were found, tumor/nontumor values generally were not distinguished by a factor of more than 1.5, suggesting that these differences may not be biologically significant. F(ab')2 fragments of NP-2 were found to be superior to NP-4 F(ab')2 fragments, giving tumor/liver and tumor/blood ratios of 16 and 11.5, respectively, within 3 days, in comparison to 5.4 and 3.8 for NP-4 F(ab')2 fragments. Mixtures of all of the MAbs or a mixture of NP-2 and NP-4 did not improve tumor localization, in comparison to NP-2 alone. These studies suggest that mixtures of these anticarcinoembryonic antigen MAbs may not afford better tumor imaging than the use of a certain single antitumor MAb. PMID- 3349461 TI - Identification of etoposide glucuronide as a major metabolite of etoposide in the rat and rabbit. AB - Isolated livers from male Sprague-Dawley rats were perfused at 20 ml/min for 3 h at 37 degrees C with 100 ml of an oxygenated, recirculating solution of 20% rat blood in Krebs bicarbonate buffer containing 20 micrograms/ml [3H]etoposide. Ninety % of administered radioactivity was eliminated in bile over a 3-h collection period. The clearance of etoposide was 3.56 ml/min indicating that, in the rat, it is not highly extracted. Its clearance is, therefore, independent of hepatic blood flow. Etoposide was both excreted into the bile and metabolized by the liver. Perfusate and bile samples analyzed by reverse-phase high-performance liquid chromatography techniques were found to contain three peaks of radioactivity. Positive and negative ion fast atom bombardment mass spectrometry identified the first two peaks as etoposide glucuronides and the third peak as parent drug. Following the i.v. administration of etoposide to rabbits, etoposide glucuronide was also identified in rabbit urine. The recovery of etoposide both from rabbit urine and rat bile was increased by preincubation with glucuronidase. However, the glucuronides were relatively resistant to the action of glucuronidase and showed varying sensitivity to the type of glucuronidase and the reaction conditions used. These studies document the presence of etoposide glucuronide as an etoposide metabolite in two mammalian species and suggest that previous clinical studies using beta-glucuronidase to quantitate glucuronide formation may have underestimated this metabolite due to its relative resistance to some glucuronidase preparations. PMID- 3349462 TI - Antiinvasive activity of estramustine on malignant MO4 mouse cells and on DU-145 human prostate carcinoma cells in vitro. AB - Estramustine (EM) is a conjugate of estradiol and nor-nitrogen mustard (nor-HN2), which is effective in the treatment of prostate cancer. We have compared the effect of EM with that of the known microtubule inhibitor vinblastine (VLB) on the following functions of malignant MO4 mouse cells and of DU-145 human prostate cancer cells in vitro: directional migration, invasion; and the organization and the assembly/disassembly equilibrium of microtubule complexes. The circular area covered by cells migrating from an aggregate explanted on a solid substrate was taken as an index of directional migration. Invasion was studied through confrontation of MO4 or DU-145 cells with fragments of embryonic chick heart in organ culture. Microtubules were investigated immunocytochemically and through immunodetection on protein blots. VLB and EM inhibited directional migration and invasion of MO4 and DU-145 cells in a dose-dependent manner; equimolar combinations of estradiol plus nor-nitrogen mustard did not mimic these effects. At anti-invasive concentrations VLB led to partial disassembly of microtubule complexes, whereas EM resulted in an abnormal pattern of microtubule complexes without alteration of the overall assembly/disassembly equilibrium. Combined treatment with VLB and EM resulted in an enhanced VLB effect, namely complete disassembly. In all tests DU-145 cells were more sensitive to both VLB and EM than were MO4 cells, and the effects were less reversible. The present experiments showed that EM shares an anti-invasive activity with other microtubule inhibitors. PMID- 3349463 TI - Effects of antileukemia agents on nuclear matrix-bound DNA replication in CCRF CEM leukemia cells. AB - The effects of various antileukemic agents on DNA replication associated with the nuclear matrix were investigated in CCRF-CEM leukemia cells. Residual nuclear matrices were prepared by sequential treatment of nuclei with 1.5 M NaCl, DNase I, and Triton X-100 and contained 1-5, 10, and 37% of the total nuclear DNA, protein, and phospholipid, respectively. In control cells pulse-labeled for 45 s with [3H]thymidine, the specific activity of nascent DNA was four-fold greater in the nuclear matrix fraction relative to the specific activity of the high salt soluble (nonmatrix) DNA fraction. Pulse-labeling and reconstitution experiments indicated that this enrichment of newly replicated DNA on the nuclear matrix did not result from aggregation of nascent DNA with the matrix. A 2-h incubation of tumor cells with either 0.1 microM teniposide (VM-26), 0.2 microM VM-26, or 0.5 microM amsacrine (m-AMSA) reduced the relative specific activity of nascent DNA on the nuclear matrix by 59, 61, and 54%, respectively, compared to control cells. In contrast hydroxyurea and cytosine arabinoside, at concentrations that markedly inhibited total nuclear DNA synthesis, did not decrease the relative specific activity of newly replicated DNA on the matrix. The results provide evidence that the antiproliferative effects of the DNA topoisomerase II inhibitors, VM-26 and m-AMSA, are localized on the nuclear matrix of CCRF-CEM leukemia cells. PMID- 3349464 TI - Uptake kinetics of monoclonal antibodies by human malignant melanoma multicell spheroids. AB - Detailed uptake kinetics by multicell spheroids of three tumor associated monoclonal antibodies was investigated. The spheroids were established from a human melanoma cell line and the human colon adenocarcinoma cell line HT29 as in vitro models of poorly vascularized micrometastases in vivo. The selected antibodies 96.5, 140.240, and OST15 showed a wide range of reactivity against the melanoma cell but they all had negligible binding with the colon cancer cell. Uptake of the antibodies by small spheroids (about 300 micron diameter) was generally sigmoidal in shape with respect to incubation time, and amount of uptake followed the same trend of immunoreactivity of the antibodies with single cells. The correlation was weaker for spheroids with diameter greater than 500 micron presumably due to the increasing size of the necrotic core. By varying the concentration of the antibodies in the incubation medium from tracer dose (0.2 microgram/ml) to a higher dose (3 micrograms/ml), negligible changes in the amount of antibodies bound with their target spheroids were observed. Nonspecific binding between antibodies and spheroids, however, resulted in proportional increase in uptake. PMID- 3349465 TI - UM-EC-1, a new hypodiploid human cell line derived from a poorly differentiated endometrial cancer. AB - The University of Michigan endometrial carcinoma cell line UM-EC-1 was derived from a poorly differentiated endometrial adenocarcinoma of a 66-yr-old white female. Cell cultures were started using both tumor explants and a cell suspension obtained from collagenase-treated tumor tissue. The collagenase derived cell suspension gave rise to monolayer cultures which grew rapidly from the outset. This subline of UM-EC-1 has now been subcultured more than 50 times. Cells derived from the tumor explants grew more slowly initially, but after a lag phase of 5 to 6 wk, this subline also exhibited rapid logarithmic growth and reached the same growth rate as that of the collagenase-treated cells. The explant subline has been subcultured more than 37 times. The doubling time of both sublines is 24 h under optimal growth conditions. The karyotype of both cell cultures is 43, XX, inv(1)(p32q42), -4, +der(8) t(8;12)(p23.1;q22), del(9)(q11), 13, -13, +t(13;13) (p13;p13), del(18)(q), -19, -22, -22, +t(22;22)(p11;p11). The net result of the chromosome losses and rearrangements was monosomy 4, duplication 8p23.1----qter, deletion 9q11----9qter, duplication 12q22----qter, deletion 18q, and monosomy 19. The t(13;13) and the t(22;22) were dicentric by C banding. Virtually all of the chromosome changes were stable in multiple passages except that there was mosaicism for chromosome 13. Some cells contained a single copy of 13 and others had t(13;13). The available evidence indicates the t(13;13) is an isochromosome. UM-EC-1 cells produced tumors histologically similar to the original tumor in male, female, and ovariectomized female athymic mice. UM-EC-1 cells express human class I histocompatibility antigens as assessed by binding of antibodies to nonpolymorphic HLA and beta-2-microglobulin antigens. Blood group antigens A and H were absent although the patient is blood type A and these antigens are normally expressed in endometrial glands. A rearrangement involving the region of chromosome nine that carries the ABH locus may be related to the absence of blood group antigen expression by these cells. The E7 membrane antigen, the locus for which resides on the short arm of chromosome 11, was expressed strongly which is consistent with the presence of two intact copies of chromosome 11 in these cells. PMID- 3349466 TI - Epithelial polarity, villin expression, and enterocytic differentiation of cultured human colon carcinoma cells: a survey of twenty cell lines. AB - Twenty human colon carcinoma cell lines were studied for their ability to develop some of the characteristics of the normal intestinal epithelium, e.g., epithelial polarity, presence of the actin-binding protein villin, or the occurrence of an enterocytic differentiation either when cultured under standard conditions, as for Caco-2 cells, or when grown in a glucose-free medium, as for HT-29 cells. Except for the regular presence of villin, which can be considered a marker of the colonic origin of the cells, the cell lines of this study could be classified into four types with regard to their differentiation characteristics. In type 1 (only one cell line, i.e., Caco-2) the cells undergo spontaneously an enterocytic differentiation characterized by a polarization of the cell layer with the formation of domes and the presence of an apical brush border the membrane of which is endowed with hydrolases such as sucrase-isomaltase, lactase, amino peptidase N, dipeptidylpeptidase IV and alkaline phosphatase. In type 2 (three cell lines: HT-29, HCT-EB, and HCT-GEO) the cells are undifferentiated when grown in the presence of glucose but undergo an enterocytic differentiation when grown in the absence of glucose. In type 3 (eight cell lines: HCT-GLY, HCT-FET, HCT FRI, HCT-CBS, HCT-ALA, Co-115, HRT-18, and SW-1116) the cells are organized into a polarized monolayer with the formation of domes but without any enterocytic differentiation characteristics, whatever the culture conditions. In type 4 (eight cell lines: HCT-116a, HCT-R, HCT-RCA, HCT-Moser, HCT-8R, SW-480, LS-174T, and Vaco-9P) the cells are organized into a multilayer without any feature of epithelial polarity or enterocytic differentiation, whatever the culture conditions. PMID- 3349467 TI - In vivo selection of highly metastatic cells from surgical specimens of different primary human colon carcinomas implanted into nude mice. AB - The purpose of these studies was to select and isolate cells with increased liver metastasizing potential from heterogeneous primary human colon carcinomas (HCCs). Cells derived from a primary HCC classified as Dukes' stage B2 were directly established in culture or were injected into the subcutis, cecum, or spleen of nude mice. Progressively growing tumors were excised, dissociated, and established in culture. Subsequent to implantation into the cecum or spleen of nude mice, cells from all four lines produced only a few liver tumor foci. HCC cells from the few liver metastases were expanded in culture and then injected into the spleen of nude mice to provide a source for further cycles of selection. With each successive in vivo selection cycle, the metastatic ability of the isolated propagated cells increased. Four cycles of selection yielded cell lines with a very high metastatic efficiency in nude mice. In parallel studies using another primary HCC classified as Dukes' stage D, we isolated cell lines that were highly metastatic in nude mice. Successive selection cycles for growth in the liver increased the metastatic properties of the HCC cells, albeit to a lesser extent than it did those of the Dukes' B2 stage HCC. The ability of the HCC cells to produce liver metastases was not due to simple trapping in the liver. In vivo distribution studies using [125I] iododeoxyuridine-labeled tumor cells revealed that, shortly after injection into the spleen, a comparable number of cells with either low or high metastatic properties arrested in the liver. The differences between the low- and high-degree metastatic cells became apparent by 24 h after injection and, by 72 h, only highly metastatic cells survived in the liver. These results demonstrate that hepatic metastasis by HCC cells is a selective process and that the nude mouse model can be useful for isolating highly metastatic HCC cells and for studying the relevant host organ factors that regulate the pathogenesis of metastasis. PMID- 3349468 TI - Risk factors for breast cancer in Chinese women in Shanghai. AB - Five hundred thirty-four histologically confirmed incident cases of breast cancer in Chinese women of Shanghai and an equal number of age and sex-matched population controls were interviewed as part of an epidemiological study of breast cancer risk factors. Early age at menarche was positively associated with breast cancer risk whereas early age at first full term pregnancy, high parity, and long duration of nursing were each negatively associated. We found high average body weight to be a risk factor, especially among women over age 60. Use of oral contraceptives after age 45 also was a risk factor, but use in general was not. Personal history of benign breast disease and history of breast cancer in first degree female relatives both increased risk. Multivariate analysis showed that each of these risk (or protective) factors was independently related to breast cancer. In addition to confirming most of the breast cancer risk factors of Western populations in a low risk developing Asian country, this study demonstrates a clear beneficial effect on breast cancer risk of lactation in a population characterized by a long cumulative duration of nursing in the majority of women. Finally, this study supports several other recent reports of a residual and beneficial effect of parity on breast cancer risk after controlling for age at first full term pregnancy. PMID- 3349469 TI - Preserved foods and nasopharyngeal carcinoma: a case-control study in Guangxi, China. AB - One hundred twenty-eight mothers of nasopharyngeal carcinoma (NPC) cases under age 45 in Yulin Prefecture, China and 174 mothers of population controls were interviewed as part of an epidemiological study to examine childhood exposures in relation to the development of NPC. Exposure before age 2 years to a number of fermented foods was a risk factor for NPC. During weaning, intake of salted fish [relative risk (RR) = 2.6, one-sided P (P) = 0.01], salted duck eggs (RR = 5.0, P = 0.03), salted mustard green (RR = 5.4, P = 0.03), and chung choi (RR = 2.0), P = 0.003), a kind of salted root, was significantly related to an increased risk of NPC. Between ages 1 and 2 years, intake frequency of dried fish [P for linear trend test (linear trend P) = 0.002], fermented black bean paste (linear trend P = 0.0009), and fermented soy bean paste (linear trend P = 0.007) was also positively associated with NPC. A multivariate analysis of these different foods showed all except fermented black bean paste to be independently related to NPC. PMID- 3349470 TI - Occupational risk factors for laryngeal cancer on the Texas Gulf Coast. AB - Analyses are reported from a case-control interview study of incident laryngeal cancer on the Gulf Coast of Texas. Study subjects were 183 white men with squamous cell carcinoma of the larynx and 250 frequency matched controls. Occupational exposures were examined controlling for potential confounding by cigarette smoking and alcohol consumption. Significantly elevated risks were seen for men employed in the public services industry [transportation, communication, utilities, sanitary service; relative risk (RR), 1.6]; in metal fabricating (RR, 2.1), construction (RR, 1.7), and maintenance (RR, 2.7) occupations; and for workers potentially exposed to paint (RR, 1.8) and diesel or gasoline fumes (RR, 1.5). Elevated risks of border-line significance were seen for men employed as woodworkers/furniture makers (RR, 8.1) and for those with occupational exposure to asbestos (RR, 1.5). When asbestos was categorized by intensity of exposure, a significant positive gradient was found. PMID- 3349471 TI - Transport, metabolism, and DNA interaction of melphalan in lymphocytes from patients with chronic lymphocytic leukemia. AB - We investigated the transport of [chloroethyl-14C]melphalan with lymphocytes from three groups of patients with chronic lymphocytic leukemia (untreated, treated sensitive, and treated resistant). There was no significant difference in the Km or Vmax of melphalan transport in lymphocytes from the three groups. In addition, there were no significant differences in intracellular melphalan levels after a 35-min incubation with 5.4 microM melphalan among the three groups. There was no evidence of intracellular metabolism of melphalan to dihydroxymelphalan except in lymphocytes from one treated sensitive patient. DL-2-Aminobicyclo[2,2,1]heptane-2 carboxylic acid, a specific analogue of the sodium-independent leucine-preferring amino acid transport system, inhibited the uptake of melphalan to a greater extent in lymphocytes from resistant patients than in those of untreated patients. Glutathione levels were not significantly different in lymphocytes from resistant patients as compared to those of untreated patients. The percentage of DNA cross-links as determined by an ethidium bromide fluorescence assay was 2-5 fold greater in lymphocytes from untreated patients than in those of resistant patients. These results suggest that resistance to the nitrogen mustards in patients with chronic lymphocytic leukemia is secondary to neither a transport defect nor alteration in intracellular melphalan levels but rather due to some other mechanism responsible for decreased DNA cross-links. PMID- 3349472 TI - Tumor markers carbohydrate antigens CA 19-9 and CA-50 and carcinoembryonic antigen in pancreatic cancer and benign diseases of the pancreatobiliary tract. AB - Sera from patients with diseases in the pancreas, gallbladder, and bile duct were analyzed for the tumor markers CA 19-9, CA-50, and carcinoembryonic antigen. In particular CA 19-9 and CA-50 appear to be valuable in differentiating malignant from benign disease in these organs. Our sample of 72 patients with pancreatic cancer also indicates that CA 19-9 and CA-50 complement each other in 21% of the cases. They are also shown to be reliable for monitoring disease: following radical surgery for pancreatic cancer low levels of CA 19-9 and CA-50 were noted, while progressive rises of these tumor markers were related to disease progression. PMID- 3349473 TI - Repair of 4,5',8-trimethylpsoralen plus light-induced DNA damage in normal and Fanconi's anemia cell lines. AB - In conditions in which solely monoadducts (MA) are induced in DNA, i.e., treatment with 4,5',8-trimethylpsoralen and 405 nm radiation, Fanconi's anemia cells (FA) appear to be more sensitive than normal human fibroblasts (1 BR/3) to cytotoxicity. The repair of such induced MA is impaired in FA compared to normal cells. When increasing the proportion of DNA interstrand cross-links (CL) over MA using a reirradiation protocol, the differential sensitivity between FA and normal human cells increases. Moreover, for a constant number of total adducts or at different ratios of CL over MA, the repair of CL is systematically hampered in FA as compared to normal cells. Incision of CL being progressively diminished by increasing amounts of MA in normal cells (D. Papadopoulo, D. Averbeck, and E. Moustacchi, Photochem. Photobiol., 47:321-326, 1988), we show here that it is even more so for FA cells. PMID- 3349474 TI - Accumulation of DNA strand breaks in cells exposed to methotrexate or N10 propargyl-5,8-dideazafolic acid. AB - N10-Propargyl-5,8-dideazafolic acid (CB 3717), a new antifolate which directly inhibits thymidylate synthase and which is now under early clinical investigation, was compared with methotrexate (MTX) for its antiproliferative activity and mode of action on M14 human melanoma cell line and NIH/3T3 murine fibroblasts transfected with human c-Ha-ras oncogene (NIH/3T3R). CB 3717 was as active as MTX on both cell lines in inhibiting colony formation, but 20-100 times less potent. After 24 h of exposure both drugs caused an accumulation of cells in the G1 phase of the cell cycle, probably because of inhibition of DNA synthesis and blockage at the G1-S boundary. In NIH/3T3R treated for 16 h with 2 microM MTX or 200 microM CB 3717, we found DNA single-strand breaks amounting to approximately 130 and 140 rad equivalents, respectively, and a considerable number of DNA double-strand breaks, far more than expected if they had been the result of the proximity of single-strand breaks on the two complementary DNA strands. No DNA-protein cross-links were detected. When cells were incubated in drug-free medium for 8 h, there was a further accumulation of single-strand breaks, possibly due to the effects of the drug retained intracellularly as polyglutamyl derivative. Simultaneous treatment with 1.77 microM cycloheximide prevented DNA damage produced by both drugs. Thymidine (10 microM), renewed in the culture medium every 24 h, also prevented DNA damage and cytotoxicity. Since after 16 h treatment with MTX or CB 3717 cells were completely viable, as assessed by [3H]thymidine release, trypan blue exclusion test, and 51Cr release, DNA damage appears to be an early event preceding cell death and may be a feature of the killing ability of the drugs. The involvement of a protein in the formation of DNA breaks is suggested by the fact that when protein synthesis was inhibited with cycloheximide DNA damage was no longer seen. PMID- 3349475 TI - Down modulation of fibronectin messenger RNA in metastasizing rat prostatic cancer cells revealed by differential hybridization analysis. AB - To identify genes whose expression is down modulated in the process of metastasis, gene expression was analyzed in cell lines derived from Dunning R 3327 rat prostatic tumor sublines. A complementary DNA (cDNA) library from the anaplastic nonmetastasizing subline AT-1 was used for a differential hybridization analysis, using probes derived from mRNAs of the AT-1 and the metastasizing MAT-LyLu subline. In this way 14 cDNA clones were isolated representing 6 differentially expressed genes. The expression levels in a panel of tumor sublines measured with these cDNA clones were tested for correlation with the anaplastic non-metastasizing phenotype. One cDNA clone, designated pSE 1, whose expression was high in all tested sublines with that phenotype, appeared to represent the gene for fibronectin. To further investigate the down modulation of this gene, we studied its expression in AT-2 (anaplastic, nonmetastasizing tumor) and lines derived therefrom that exhibited a high metastatic potential after transfection with the v-Ha-ras oncogene. In the genetically manipulated metastasizing tumor sublines, fibronectin mRNA levels were approximately 4- to 8 fold lowered compared to the nonmetastasizing parental AT-2 line. PMID- 3349476 TI - Oxygen dependent regulation of DNA synthesis and growth of Ehrlich ascites tumor cells in vitro and in vivo. AB - Ehrlich ascites cells were cultured under different O2 partial pressures from less than 0.1 ppm to 2 x 10(5) ppm. During the artificial hypoxia and following reoxygenation the DNA synthesis rate was measured and the relative frequency of replicon initiations was examined by analyzing the length distributions of replicative daughter strand DNA. These studies were complemented by evaluation of growth and cycling of the cells and by biochemical analyses. It was demonstrated that the reversible shut-down of clusters of replication units already described before (Probst, H., Gekeler, V., and Helftenbein, E. Exp. Cell Res., 154: 327 341, 1984) occurred between 0.25 and about 2.5 microM dissolved O2. Above 2.5 microM, a transition range to aerobiosis extended to about 16 microM O2. Below 0.25 microM O2, the cells suffered damage impairing the reversibility of the shutdown. The observed changes of growth and cycling correlated well with the respective changes of replication. Analogous oxygenation dependent regulatory events in replication were also observed during growth of the cells as an in vivo ascites tumor. Obviously, the particular oxygenation conditions in the peritoneal cavity strongly influence tumor growth via the oxygen dependent regulation of replication. PMID- 3349477 TI - Anticarcinoma activity of rhodamine 123 against a murine renal adenocarcinoma. AB - The mitochondria of carcinoma cells retain the permeant cationic compound rhodamine 123 longer than the mitochondria of normal epithelial cells. The possibility of exploiting this difference in the chemotherapy of a murine renal adenocarcinoma was investigated. Rhodamine 123 exhibited anticarcinoma activity in mice and this activity was potentiated by 2-deoxyglucose and methylglyoxal bis(guanylhydrazone), a chemotherapeutic agent that is toxic to mitochondria. Prolonged retention of rhodamine 123 by renal tumor cells compared with normal renal epithelial cells was demonstrated by flow cytometry, perhaps explaining its antitumor activity. A combination of both mitochondrial toxins, rhodamine 123 and methylglyoxal bis(guanylhydrazone) produced the longest survival and had the greatest antitumor effect. PMID- 3349478 TI - Reversal of resistance to vincristine in P388 leukemia by various polycyclic clinical drugs, with a special emphasis on quinacrine. AB - We investigated several lipophilic drugs with a polycyclic structure for their effect on the net uptake of vincristine in vincristine-resistant P388 leukemia cells. Fourteen of 23 agents promoted vincristine uptake in the resistant cells. The net increase in vincristine uptake was caused by prevention of its outward transport rather than by stimulation of inward transport. Some of these drugs, e.g., quinacrine, dilazep, syrosingopine, simetride, etc., remarkably potentiated the cytotoxicity of vincristine against the resistant cells in vitro. Quinacrine, an antimalarial drug which had the greatest effect on vincristine uptake and relatively low host toxicity, exhibited potent therapeutic synergism in combination with vincristine in resistant leukemia-bearing mice. PMID- 3349479 TI - Increased levels of fibroblast growth factor-like activity in urine from patients with bladder or kidney cancer. AB - Growth factor activity was partially purified from human renal tumors and a human bladder cancer cell line by heparin-Sepharose chromatography. This activity stimulated bovine capillary endothelial cell proliferation and DNA synthesis in BALB/c 3T3 cells. Partially purified growth factor preparations from these tumors contained a protein with an approximate molecular weight of 17,000 which was recognized by a polyclonal antiserum raised against a peptide fragment of basic fibroblast growth factor (FGF). This growth factor activity appears to be related to basic fibroblast growth factor. Measurement of FGF-like activity in 50 urine samples from 32 adult males showed that 55% (6 of 11) of the urine samples from patients with bladder cancer and 100% (7 of 7) of the urine samples from patients with kidney cancer contained activity equivalent to more than 20 ng of basic FGF/h of urine production. In contrast, only 6% (2 of 32) of the urine samples from controls, patients with a benign disease, or patients with a history of bladder or kidney cancer contained this level of growth factor activity. These results suggest that patients with bladder or kidney cancer release an FGF-like factor into urine which may be used as a marker for these tumors. PMID- 3349480 TI - Dose-response study with N-nitrosomorpholine in drinking water of F-344 rats. AB - A dose-response study in carcinogenesis was carried out with N-nitrosomorpholine in female F344 rats. The compound was administered in drinking water, which was supplied in controlled amounts of 20 ml per day per rat, 5 days a wk. At the two highest dose rates, 100 mg/liter and 40 mg/liter, treatment lasted 25 and 40 wk, respectively. At the other dose rates, which differed by a factor of 2.5, treatment lasted 50 or 100 wk. The average total dose received by each rat ranged from 250 mg to 0.7 mg. There were 100 animals per group at the lowest dose rates and 24 animals per group at the highest dose rates. Total doses of nitrosomorpholine above approximately 30 mg per rat caused a statistically significant decrease in survival, but at lower doses survival was similar to that of untreated controls. In nearly all of the treated groups there was a statistically significant increase in the incidence of benign or malignant hepatocellular neoplasms, with a highly significant dose-related trend. At the higher doses there was a significant incidence of hemangiosarcomas of the liver. Both hepatocellular carcinomas and hemangiosarcomas metastasized to the lungs and other organs. At the highest doses there was a significant incidence of neoplasms of the tongue and esophagus, which were rarely seen at the lower doses. The results suggest that even the lowest dose of nitrosomorpholine received by the rats, 0.7 mg or approximately 3 mg/kg body weight, was not a no-effect dose during the 2-yr lifetime of a rat. Probit analysis of the results indicate a dose estimated to cause tumors in 50% of the population of 25 mg nitrosomorpholine for liver neoplasms. PMID- 3349481 TI - Effects of hyperthermia on cell survival and patterns of protein synthesis in endothelial cells from different origins. AB - Thermotolerance, transient resistance to heat induced by heat itself, is generally thought to be linked to the accumulation of heat-shock proteins in eukaryotic cells. The induction of thermotolerance and the synthesis of heat shock proteins in primary and passage cultures of bovine aortic endothelium, passage cultures of bovine brain capillaries, and passage cultures of rat epididymal capillaries were examined. Primary and passage cultures of bovine aortic endothelial cells readily acquired thermotolerance; however, passage cultures of rat epididymal capillary cells and bovine brain capillary cells were very heat sensitive. In all endothelial cell types examined except rat epididymal capillary cells, the levels of HSP71, the most inducible of the HSP70 family, correlated well with thermotolerance. With prolonged passage, rat epididymal capillary cells and bovine brain capillary cells lost their ability to acquire heat resistance. Endothelial cells from different origins (aortic endothelium versus capillary endothelium) but from the same species and about the same passage number had a notably different response in terms of thermotolerance and synthesis of proteins after exposure to hyperthermia. The results of this study suggest that, while the expression of HSP71 may be a good indicator of heat resistance, the reverse is not necessarily true. Furthermore, the data show that endothelial cells from different origins are dissimilar in their response to hyperthermia. PMID- 3349482 TI - Cerebrospinal fluid penetration of active metabolites of cyclophosphamide and ifosfamide in rhesus monkeys. AB - The penetration of the active metabolites of cyclophosphamide (CP) and ifosfamide (IF) into cerebrospinal fluid (CSF) was determined in rhesus monkeys following an i.v. infusion of 1 gm/m2 of CP and IF. Active metabolites were measured using a high-performance liquid chromatography assay with fluorometric detection following derivatization with m-aminophenol. CSF to blood ratios of the active metabolites of CP and IF were found to be 0.17 and 0.13 following systemic dosing of CP and IF, respectively. The levels achieved in the CSF, however, were equivalent to levels known to be cytocidal to malignant cell lines derived from tumors which metastasize to the central nervous system. Only one animal demonstrated neurotoxicity with IF. CSF levels of active metabolite in this animal were similar to those observed in the other animals. PMID- 3349483 TI - Effect of radiation-induced injury of tumor bed stroma on metastatic spread of murine sarcomas and carcinomas. AB - The study was performed to determine whether irradiation of the tumor bed alters the propensity of tumors to metastasize, and if so, whether the effect is dependent on the property of tumors to exhibit the tumor bed effect (TBE). Ten tumors, of which 5 were sarcomas and 5 were carcinomas syngeneic to C3Hf/Kam mice, were used. Tumors were grown s.c. in the right thighs of mice that had or had not been irradiated with 20-Gy gamma-rays 1 day before tumor cell transplantation. All 5 carcinomas and 2 of 5 sarcomas exhibited TBE, as assessed by a significant retardation of growth rate. To test whether irradiation of the tumor bed influenced metastatic spread independently of TBE, tumors of various sizes were surgically removed, and at appropriate times thereafter the lungs were examined for the presence of metastases. All tumors that exhibited TBE, and only 1 of 3 tumors that did not exhibit TBE, metastasized more than tumors of the same size growing in an unirradiated tumor bed. TBE-induced enhancement of metastasis was not seen in tumors less than approximately 7 mm in diameter. All tumors, whether they exhibited TBE or not, were more necrotic if they grew in a preirradiated tumor bed. These observations show that size for size, most tumors growing in irradiated tissues have an increased propensity to metastasize, which is linked to their manifestation of TBE. The evidence presented suggests that TBE induced retardation of tumor growth is the major factor responsible for the observed enhancement of metastasis. The clinical implication of these findings is that tumors recurrent after radiotherapy should be diagnosed and treated promptly to reduce the risk of metastatic spread. PMID- 3349484 TI - Antioxidant enzymes in xeroderma pigmentosum fibroblasts. AB - In light of recent studies implicating low catalase activities in the pathogenesis of the cancer-prone disease xeroderma pigmentosum (XP) we have measured catalase activity, protein levels, and mRNA concentrations in six XP fibroblast strains and three normal controls. Only one XP strain of complementation group A (XP1223) possessed significantly lower catalase by all three criteria. The other five XP strains (two XP variants, two strains of complementation group D, and one strain of complementation group C) possessed catalase levels which fell into the range of the interindividual variations of normal controls. We further assessed the total enzymatic antioxidant defense status by measuring the levels of copper, zinc, and manganese superoxide dismutase and glutathione peroxidase. None of these enzymes showed significant deviations from controls in XP cells. Our results do not support the notion that a deficient enzymatic antioxidant defense facilitates the establishment of a prooxidant state in XP upon exposure to near-UV. However, they do not argue against the participation of active oxygen in near-UV-induced carcinogenesis in XP. PMID- 3349485 TI - O6-alkyldeoxyguanosine detection by 32P-postlabeling and nucleotide chromatographic analysis. AB - The 32P-postlabeling procedure, developed originally by Randerath and coworkers, has been modified for the detection and analytical quantitation of O6-alkyl-2' deoxyguanosine residues in DNA. Chromatographic techniques were developed to resolve individually the normal deoxyribonucleotide-3'-monophosphates and the O6 alkyldeoxyguanosine-3'-monophosphates by high-pressure liquid chromatography. Selective deoxyribonucleotide-3'-monophosphates (e.g., O6-alkyldeoxyguanosine-3' monophosphates) were then converted to labeled deoxyribonucleotide-[5' 32P]monophosphates by 32P-postlabeling and nuclease P1 treatment and separated by two-dimensional thin layer chromatography. The O6-methyl- and O6-ethyl-2' deoxyguanosine-3'-monophosphate nucleotides, and the respective 5' monophosphates, were chemically synthesized for standardization of these quantitative procedures. The quantitation of O6-methl- and O6-ethyl-2' deoxyguanosine was observed to be analytically accurate between one O6-alkyl-2' deoxyguanosine residue per 10(4) and 10(7) 2'-deoxyguanosines. The limit of detection was less than one O6-alkyl-2'-deoxyguanosine in 10(7) 2'-deoxyguanosine residues in a sample size of 100 micrograms of DNA, i.e., approximately 10 pg of adduct. The quantitation of O6-methyl-2'-deoxyguanosine in the liver DNAs of rats treated with [14C-Me]N-nitrosodimethylamine compared well with values obtained by both 14C and high-pressure liquid chromatography coupled with fluorescence detection. Thus, these 32P-postlabeling and nucleotide chromatographic procedures should be useful in monitoring human exposure to methylating and ethylating carcinogens. PMID- 3349486 TI - Carcinogenicity of deuterium-labeled 1,2-dimethylhydrazine in mice. AB - To study the effect of deuterium substitution on the carcinogenicity of 1,2 dimethylhydrazine (DMH) in mice, two comparisons were made between DMH and its fully methyl-deuterated analogue, [2H6]DMH. In a lifetime study with the CBA strain, groups of 19-30 animals of each sex were dosed s.c. weekly with 8 mg/kg of either DMH or [2H6]DMH for 8, 16, or 32 weeks. In the second study, female CF 1 mice were given DMH or [2H6]DMH in 10 weekly s.c. doses of 12 mg/kg each (13.2 mg/kg for [2H6]DMH) and examined for colon tumors 36 weeks after the first dose. Deuteration significantly decreased tumor incidence in the colon of males (P less than 0.01) and the anal tissue of both sexes (P less than 0.05) but increased that of hepatomas and lung tumors in males (P less than 0.01). Substrate deuteration did not significantly affect overall incidence of any other tumor type, however, including hemangioendotheliomas and kidney tumors in both sexes, as well as colon, uterine, ovarian, liver, and lung tumors in females. The results indicate that C--H bond breakage is kinetically important in the activation of DMH to its ultimately carcinogenic form in organs such as the male colon (relative risk in DMH-versus [2H6]DMH-treated animals approximately equal to 6), and that inhibition of this process by substrate deuteration allows a diversionary mechanism having a smaller isotope effect to become relatively more extensive. The qualitatively different effect in other organs (e.g., kidney, relative risk approximately equal to 1) supports recent suggestions that the net mechanism of activation can differ from one target tissue to another, possibly by striking a different balance between parallel metabolic pathways. The lack of a significant isotope effect on overall colon tumor incidence in females of either strain suggests that differences in relative importance among competing enzymes may also be responsible for sexual dimorphism in tumor induction by DMH. PMID- 3349488 TI - Toxic effect of tumor necrosis factor on tumor vasculature in mice. AB - Stereoscopic observation via an implanted sight glass in mice bearing transplanted methylcholanthrene-induced A-cells showed tumorivascular hemorrhage at 1-2 h after tumor necrosis factor (TNF) administration, congestion at 4-6 h, and hemorrhage, congestion, and blood circulation blockage at 24 h. Histological examination after TNF administration to mice bearing similar methylcholanthrene induced A-cell transplants showed thrombus formation in the tumor vasculature at 4 h and thereafter. Suppression of this thrombus formation with heparin had no apparent influence on the necrotic response, tumor growth inhibition or complete cure rate following TNF administration to mice bearing the methylcholanthrene induced A-cell tumors. The results suggest that direct toxicity of TNF on tumor vasculature is a factor in the overall antitumor mechanism of TNF. PMID- 3349487 TI - Inhibition of tumor promoter 12-O-tetradecanoylphorbol-13-acetate-induced synthesis of epidermal ornithine decarboxylase messenger RNA and diacylglycerol promoted mouse skin tumor formation by retinoic acid. AB - Evidence is presented that inhibition of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC; EC 4.1.1.17) by retinoic acid may involve inhibition of protein kinase C-mediated synthesis of ODC mRNA. A single application of 10 nmol of TPA to intact mouse skin led to an increase in the steady state levels of epidermal ODC mRNA; a maximal level of ODC mRNA occurred at about 3.5 h after TPA treatment. TPA-induced increase in ODC mRNA preceded the increase in epidermal ODC activity. Application of 17 nmol of retinoic acid 1 h before application of TPA to mouse skin inhibited the induction of both ODC mRNA and ODC activity. Using the DNA-excess filter hybridization technique, we found that TPA-increased steady state levels of ODC mRNA in primary culture of newborn mouse epidermal cells were the result of enhanced accumulation of newly synthesized ODC mRNA. Furthermore, in a pulse-chase experiment, we could not detect any difference in the half-life of ODC mRNA in epidermal cells after TPA or the vehicle dimethyl sulfoxide treatments; the half-life of ODC mRNA was about 7 h in both cases. Exposure of primary cultures of newborn epidermal cells to retinoic acid, in conjunction with TPA, inhibited the synthesis of ODC mRNA and failed to alter the half-life of ODC mRNA. These results implicate the role of transcription activation in TPA-induced ODC gene expression and indicate that retinoic acid may inhibit TPA-induced ODC gene transcription. We also found that protein kinase C may play a role in the mechanism of inhibition by retinoic acid of ODC gene expression. Supporting evidence is the finding that L-alpha dioctanoylglycerol, an activator of protein kinase C, is a Stage II mouse skin tumor promoter and the application of retinoic acid 1 h before application of L alpha-dioctanoylglycerol to mouse skin inhibited the induction of ODC activity and ODC mRNA as well as tumor promotion by L-alpha-dioctanoylglycerol. Taken together, one may conclude that the mechanism of inhibition of TPA-induced ODC by retinoic acid may involve the inhibition of protein kinase C-mediated accumulation of newly synthesized ODC mRNA. PMID- 3349489 TI - o-(beta-Hydroxyethyl)-rutoside-mediated protection of renal injury associated with cis-diamminedichloroplatinum(II)/hyperthermia treatment. AB - A bioflavonoid, o-(beta-hydroxyethyl)-rutoside, has been investigated for its potential to increase the therapeutic index of the combined treatment modalities of whole body hypothermia (WBH) (41.5 degrees C) and chemotherapy (cisplatin) in studies utilizing a transplantable fibrosarcoma solid tumor model in Fischer rats. When whole body WBH was induced 45 min after cisplatin administration, a significantly increased tumor growth delay was noted beyond that achieved by either treatment modality alone. The combination of WBH and cisplatin treatments, however, produced an unacceptable increase in renal injury. o-(beta-Hydroxyethyl) rutoside administration was found to effectively block the renal injury without interfering with the antitumor efficacy of the combined regimen. Potential explanations for the ability of o-(beta-hydroxyethyl)-rutoside to affect the increase in WBH-cisplatin therapeutic regimen are discussed. PMID- 3349490 TI - Loss of a Mr 78,000 marker in chemically induced transplantable carcinomas and primary carcinoma of human pancreas. AB - Toward the identification of steps in the multiphasic process of human pancreas carcinogenesis we have developed a panel of monoclonal antibodies to normal and carcinogen-treated human pancreas cells. One of these, an IgG3 with strong affinity for a membrane-associated Mr 78,000 protein in fetal and adult parenchymal cells, was purified by high performance liquid chromatography, and used for the detection and characterization of tumorigenic stage in human pancreas carcinogenesis. This protein was present on the cell surface of human pancreas explants exposed to methylnitrosourea for up to 4 months and in nontumorigenic cell lines derived from these explants. It was absent in a morphologically transformed subpopulation of cells in explants treated with methylnitrosourea for longer than 4 months, in tumorigenic cell lines derived from these explants, and in primary carcinomas of human pancreas. The presence of this marker in normal pancreas adjacent to tumors, in hyperplastic cells induced by methylnitrosurea and in nontumorigenic cell lines suggests a correlation between the loss of this membrane-associated marker and cell tumorigenicity. PMID- 3349491 TI - Alcohol consumption and the risk of breast cancer in a prepaid health plan. AB - We examined breast cancer incidence in a cohort of about 69,000 women who were members of a large prepaid health plan in Northern California and who answered detailed questions about alcohol consumption from 1979 through 1984 as part of a voluntary multiphasic health checkup. Among white, black, and Hispanic women with no prior cancer, breast cancer had developed in 303 by the end of 1984. In analysis controlling only for age there was a progressive increase in breast cancer incidence with each higher level of reported alcohol consumption. In multivariate analyses controlled for age, race, body mass, and smoking, the relative risk at 1-2 drinks per day was 1.5 [95% confidence interval (CI) 1.0 2.3], at 3-5 drinks per day it was 1.5 (95% CI 0.8-2.8), and at 6 or more drinks per day it was 3.3 (95% CI 1.2-9.3). Past drinkers tended to have been heavier drinkers than current drinkers and had a relative risk of 2.2 (95% CI 1.2-3.9). Study of wine, beer, and liquor use did not suggest that any particular alcoholic beverage was responsible. Significant associations with heavy alcohol consumption were strongest among white, and among postmenopausal women. This study adds support to the growing evidence that alcohol may be a risk factor for development of breast cancer. PMID- 3349492 TI - A pediatric phase I and pharmacokinetic study of spirohydantoin mustard. AB - A pediatric Phase I and pharmacokinetic study of the lipophilic alkylating agent spirohydantoin mustard (SHM) was conducted in 23 patients. The dose-limiting toxicity of SHM was neurological with disorientation, delirium, or hallucinations occurring in 9 of 23 patients. These symptoms were partially reversible and preventable with physostigmine. In 17 patients who were evaluable for response to treatment (14 of whom had central nervous system malignancies), no objective tumor responses were observed. Pharmacokinetic evaluation of SHM revealed a t1/2 alpha of 1.7 +/- 0.7 min, t1/2 beta of 16 +/- 8.3 min, and total body clearance of 2134 +/- 735 ml/min/m2. Measureable peak plasma levels were less than 40% of that which produces cytotoxicity in vitro against monolayer cultures of rat 9L brain tumor. Over 90% of SHM was protein bound, greatly limiting the free drug available for central nervous system penetration. SHM cerebrospinal fluid to plasma ratios were less than 0.047. The above suggests that in spite of its lipophilicity, SHM may not reach clinically significant levels in the central nervous system at clinically tolerable doses. PMID- 3349493 TI - Plasma gastrin responses to bombesin and antral gastrin concentrations in patients with the intestinal type of gastric cancer. AB - Mucosal atrophy of the gastric antrum (type B atrophic gastritis) is generally accepted as predisposing to the development of the intestinal type of gastric cancer. Since bombesin stimulates gastrin release selectively from the antral mucosa, the response can be used as a marker for antral mucosal atrophy. In this study we have investigated bombesin-stimulated plasma gastrin responses in 21 patients with the intestinal type of gastric cancer and we have compared the results with 12 patients with the diffuse type of gastric cancer, 17 patients with benign gastric ulcer, and 30 dyspeptic patients without endoscopical or histological abnormalities. Gastrin concentrations were also measured in extracts of antral biopsies. Basal plasma gastrin concentrations were not significantly different. In contrast, patients with the intestinal type of gastric cancer had a significantly lower plasma gastrin response to bombesin than did the normal subjects (P less than 0.01) and patients with the diffuse type of gastric cancer (P less than 0.05), but the result was not significantly different from that of the gastric ulcer patients. The antral gastrin content of the patients with the intestinal type of gastric cancer was significantly lower than in controls (P less than 0.005), the patients with the diffuse type of gastric cancer (P less than 0.05), and those with gastric ulcer (P less than 0.05). It is concluded that patients with the intestinal type of gastric cancer have, in contrast to those with the diffuse type of gastric cancer, an abnormally low plasma gastrin response to bombesin. This low response is due to a reduced gastrin content of the antral mucosa. PMID- 3349494 TI - Relationship between papillary and nodular transitional cell carcinoma in the human urinary bladder. AB - A total of 186 cystectomized specimens were examined by step-sectioning to determine the relation between papillary and nodular transitional cell carcinomas of the urinary bladder. Tumors were classified as papillary (PC), nodular (NC), and carcinoma in situ (CIS) according to their gross and microscopic configurations. These cases, grouped as simple combinations of PC, NC, and CIS, namely, PC, PC + CIS, PC + NC, PC + NC + CIS, NC, NC + CIS, and CIS, were analyzed with respect to (a) the time from the initial symptom to cystectomy, (b) the treatment before cystectomy, (c) the grade, (d) the stage of tumors, (e) the multiplicity of tumors, (f) the presence of papillary structures inside or on the surface of nodular carcinoma, and (g) data on survival after cystectomy. Of the tumors, 17 were classified as CIS and 80 as PC and PC + CIS. Studies on 57 cases suggested an early change from PC to a mixture of PC and NC through papillonodular carcinoma during development, whereas 6 showed late development of NC during repeated recurrence of PC. These courses indicate that some cases of NC developed from PC. On the other hand, 26 cases exhibited direct progression from CIS to NC. Thus nodular invasive carcinomas may develop in two ways: by emergence of a more anaplastic cell population within a preexisting low grade papillary carcinoma; and by de novo development of an invasive nodular carcinoma directly from CIS. PMID- 3349495 TI - Identification of 4-hydroxy-N-desmethyltamoxifen as a metabolite of tamoxifen in human bile. AB - The occurrence of tamoxifen metabolites in bile was investigated in a 57-year-old female patient receiving chronic treatment with tamoxifen. In bile treated with beta-glucuronidase, two major peaks were detected using a chromatographic system developed for the quantitation of tamoxifen metabolites in human serum. One sharp peak coeluted with 4-hydroxy-tamoxifen whereas a second broad peak eluted slightly ahead of tamoxifen and was separated from all major serum metabolites. This latter peak was identified as the cis (about 30%) and trans (about 70%) isomers of 4-hydroxy-N-desmethyltamoxifen. The identification was based on (a) coelution with authentic standard on reversed-phase chromatography and formation of fluorescent material after photoactivation, (b) a molecular ion (M + 1)+ of 374 m/z as determined with liquid chromatography-mass spectrometry, and (c) a fragmentogram identical to that of the authentic standard, as obtained by gas chromatography-mass spectrometry. PMID- 3349496 TI - Continuous duodenal infusions of levodopa: plasma concentrations and motor fluctuations in Parkinson's disease. AB - Four parkinsonian patients received continuous duodenal infusions of levodopa (LD) for severe "on-off" phenomena associated with Sinemet (carbidopa/levodopa) therapy. All patients had marked decreases in motor fluctuations on the infusions compared with tablets. Two factors that appear related to this improvement are the ability of duodenal infusions to produce steadier plasma LD concentrations and/or to maintain LD concentrations above a minimum threshold needed to achieve the "on" state. PMID- 3349498 TI - Lack of pharmacokinetic influence on levodopa by bromocriptine. PMID- 3349497 TI - Does anisocoria by clonidine reflect a central sympathetic dysfunction in cluster headache? AB - Local pharmacological manipulations of both pupils in persons with cluster headache (CH) have shown a reduced pain-side sympathetic activity. It is difficult to determine if this sympathetic defect is localized in the nuclei of the CNS and/or in peripheral neurons that innervate the pupil. This study demonstrates that in a CH group 2% tyramine (an intraneuronal norepinephrine releaser) instillation into both eyes induces an asymmetric and bilateral mydriasis with the onset of anisocoria characterized by a pupillary diameter being less on the pain-side eye. In addition, intravenous administration of 0.10 mg clonidine, an inhibitor of central sympathetic activity, causes a bilateral miotic response, which is more marked on the pain-side eye. In a healthy control group, clonidine induces a symmetric and bilateral miosis but less intense than that observed in both eyes of CH sufferers. In CH patients, pretreatment with clonidine augments the degree of anisocoria induced by tyramine instillation, increasing the mydriatic response only in the pain-free-side pupil. The hypothesis of a permanent sympathetic defect of the pain-side pupil expressing itself as a reduced sympathetic tone of CNS nuclei and peripheral neurons that innervate the pupil is proposed. PMID- 3349499 TI - Methysergide-induced akathisia. PMID- 3349500 TI - Iodine binding to amylodextrin fractions studied by difference spectrophotometry and potentiometry. PMID- 3349501 TI - Synthesis of the isomeric trisaccharides, methyl O-alpha-L-fucopyranosyl- (1--- 3, 4, and 6)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-beta- D galactopyranoside. AB - Benzylation of methyl 3-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D- glucopyranosyl)-2,4,6-tri-O-benzyl-beta-D-galactopyranoside with benzyl bromide in N,N-dimethylformamide in the presence of sodium hydride afforded methyl 3-O- (2-acetamido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl) -2,4,6- tri-O-benzyl-beta-D-galactopyranoside (3). Reductive ring-opening of the benzylidene group of 3 gave methyl 3-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-beta D- glucopyranosyl)- 2,4,6-tri-O-benzyl-beta-D-galactopyranoside (4). Cleavage of the 4,6-acetal group of 3 with hot, 80% aqueous acetic acid afforded the diol (5). Compounds 3, 4, and 5 were each subjected to halide ion-catalyzed glycosylation with 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide to produce the corresponding trisaccharide derivatives, which, on catalytic hydrogenation, furnished the title trisaccharides, respectively. PMID- 3349502 TI - Synthesis of methyl glycoside derivatives of tri- and penta-saccharides related to the antithrombin III-binding sequence of heparin, employing cellobiose as a key starting-material. AB - Two key synthons for the title pentasaccharide derivative, methyl O-(methyl 2-O benzoyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-acetyl- 2-azido - 3 O- benzyl-2-deoxy-beta-D-glucopyranoside and O-(methyl 2,3-di-O-benzyl-4-O- chloroacetyl-beta-D-glucopyranosyluronate)-(1----4)-3,6-di-O-acetyl-2-az ido-2- deoxy-alpha-D- glucopyranosyl bromide, were prepared from a common starting material, cellobiose. They were coupled to give a tetrasaccharide derivative that underwent O-dechloroacetylation to the corresponding glycosyl acceptor. Its condensation with the known 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D glucopyranosyl bromide afforded a 77% yield of suitably protected pentasaccharide, methyl O-(6-O- acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D glucopyranosyl)-(1----4)- O- (methyl 2,3- di-O-benzyl-beta-D glucopyranosyluronate)-(1----4)-O-(3,6-di-O-acetyl-2- azido-2 - deoxy-alpha-D glucopyranosyl)-(1----4)-O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L- idopyranosyluronate)- (1----4)-6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-beta-D glucopyranoside. Sequential deprotection and sulfation gave the decasodium salt of methyl O-(2- deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1----4)-O (be ta-D- glucopyranosyl-uronic acid)-(1----4)-O-(2-deoxy-2-sulfamido-3,6-di-O sulfo-alpha-D-gluco pyranosyl)- (1----4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1----4)-2-deoxy-2- sulfamido-6-O- sulfo-beta-D-glucopyranoside (3). In a similar way, the trisaccharide derivative, the hexasodium salt of methyl O-(2 deoxy-2-sulfamido-6-O-sulfo-alpha-D- glucopyranosyl)- (1----4)-O-(beta-D glucopyranosyluronic acid)-(1----4)-2-deoxy-2-sulfamido-3,6- di-O- sulfo-alpha-D glucopyranoside (4) was synthesized from methyl O-(6-O-acetyl-2- azido- 3,4-di-O benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2,3-di-O- benzyl-beta- D-glucopyranosyluronate)-3,6-di-O-acetyl-2-azido-2-deoxy-alpha-D- glucopyranoside. The pentasaccharide 3 binds strongly to antithrombin III with an association constant almost equivalent to that of high-affinity heparin, but the trisaccharide 4 appears not to bind. PMID- 3349503 TI - The complete structure of the trifoliin A lectin-binding capsular polysaccharide of Rhizobium trifolii 843. AB - The complete structure of the acidic, extracellular, capsular polysaccharide of Rhizobium trifolii 843 has been elucidated by a combination of chemical, enzymic, and spectroscopic methods, confirming an earlier proposed sugar sequence and assigning the locations of the acyl substituents. The polysaccharide was depolymerized by a lyase into octasaccharide units which were uniform in carbohydrate composition and linkage. These units also contained a uniform distribution of acetyl and pyruvic acetal [O-(1-carboxyethylidene)] groups, and half of them were further acylated with D-3-hydroxybutanoyl groups. A much smaller proportion (less than 5%) of the oligomers was further acylated by a second D-3-hydroxybutanoyl group. The locations of the subtituents were determined chemically and by J-correlated, 1H-n.m.r. spectroscopy, proton nuclear Overhauser effect (n.O.e.) measurements, double-rd structure of the carbohydrate chain were determined by methylation analysis using g.l.c.-m.s. fast-atom bombardment mass spectrometry, and n.m.r. studies on the reduced, deacylated oligomer. Structural studies were supplemented by n.m.r. analyses on the original polymer. The oligosaccharides were found to be branched octasaccharides with four sugar residues in each branch, and the carbohydrate sequence agreed well with that expected from earlier work. In the abbreviated sequence and structure (1a), the sugar residues are labelled "a" through "h". The main chain (a-d) is composed of a 4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid group (a) that is linked to O-4 of a 3-O-acetyl-D-glucosyluronic acid residue (b) which is beta-linked to O-4 of a D-glucosyl residue (c). Residue c is beta-linked to O-4 of the branching D-glucose residue (d). The side chain consists of a substituted D-galactosyl group (h) which is beta-linked to O-3 of residue 9 of a beta-(1----4)-linked D glucose trisaccharide (fragment e-f-g). The reducing end of the resulting tetrasaccharide (e-f-g-h) is beta-linked to O-6 of the branching D-glucose residue (d). In the native polymer, this branching residue is alpha-linked to O-4 of the modified D-glucuronic acid residue (a) which is the unsaturated sugar in the oligomer. A small proportion of the O-2 atoms of the acetylated D glucosyluronic acid residues is acetylated because of ester migration. The two terminal sugars (g and h) of the branch chain bear 4,6-O-(1-carboxyethylidene) groups. The D-galactosyl groups of half of the oligomers are acylated by D-3 hydroxybutanoyl groups at O-3.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3349504 TI - Writing a research proposal: the first step in conducting research. Part 2. PMID- 3349505 TI - [Modern immuno-analytical methods based on fluorescence detection and light scattering]. PMID- 3349506 TI - [Serum cholesterol in patients with carcinoma of the lungs]. PMID- 3349507 TI - [Quantitative assessment of proteinuria from a single sample of urine]. PMID- 3349508 TI - [Solitary plasmacytoma of the mastoid process]. PMID- 3349509 TI - [Problems and new findings in genetic research on primary affective disorders]. PMID- 3349511 TI - [New trends in the basic treatment of rheumatoid arthritis]. PMID- 3349510 TI - [Empirical risks in the development of diabetes. Genealogical studies in type 2 diabetics]. PMID- 3349512 TI - Does intracoronary papaverine dilate epicardial coronary arteries? Implications for the assessment of coronary flow reserve. AB - Intracoronary papaverine is used as a means to induce a strong and short-lasting hyperemia in several recently developed methods to measure coronary flow reserve. Changes in stenosis geometry from papaverine would influence the measured coronary flow reserve. Therefore, we investigated the influence of intracoronary papaverine on stenosis geometry with quantitative analysis of the coronary angiogram and assessed the influence of papaverine on pressure-flow characteristics of the stenosis and coronary flow reserve. The cross-sectional areas (mean +/- SD) of the stenosis increased 18% +/- 7% after papaverine. The normal proximal and distal parts of the coronary artery dilated 5% +/- 2% after papaverine. This results in a decrease of the calculated pressure drop over the stenosis varying from 20% to 30%. Coronary flow reserve of a flow-limiting epicardial stenosis is overestimated by 16% when papaverine is used to induce hyperemia. These papaverine-induced changes can nevertheless be circumvented by maximal vasodilation of the major epicardial coronary artery with 3 mg intracoronary isosorbidedinitrate prior to the investigation of the coronary flow reserve with papaverine. PMID- 3349513 TI - The safety of protamine sulfate in diabetics undergoing cardiac catheterization. AB - The frequency of anaphylactoid reactions to protamine sulfate was examined by reviewing the records of diabetic patients undergoing cardiac catheterization over a 5-year period, and by prospectively monitoring diabetic patients receiving NPH insulin during the infusion of protamine sulfate. No anaphylactoid reactions were noted after protamine administration (48 +/- 5 mg) in the retrospective study in either patients with prior exposure to protamine (74 catheterizations) or in diabetics with no exposure to protamine (132 catheterizations). In the prospective study, no anaphylactoid reactions were seen in the 24 NPH insulin dependent diabetics during the infusion of protamine sulfate (45 +/- 5 mg). Five of the 42 patients (12%) from the retrospective study who underwent vascular surgery developed severe reactions to much larger doses of protamine (380 +/- 118 mg). Diabetics with prior exposure to protamine sulfate do not appear to be at increased risk of anaphylactoid reaction after the administration of protamine sulfate in the dose range of less than 50 mg at the time of cardiac catheterization. PMID- 3349514 TI - Pulsus alternans induced by inferior vena caval occlusion in man. AB - To assess the effect of rapid preload reduction on left ventricular performance in nonischemic cardiomyopathy, 11 patients were studied during inferior vena caval (IVC) balloon occlusion. Five developed sustained pulsus alternans. During pulsus alternans, the strong beats demonstrated systolic performance characteristics similar to baseline values, despite a drop in both left ventricular (LV) end-diastolic diameter (66 +/- 13 to 61 +/- 13 mm; p less than 0.05) and LV end-diastolic pressure (21 +/- 8 to 9 +/- 6 mmHg; p less than 0.05). In contrast, the weak beats demonstrated a reduction in peak systolic pressure (130 +/- 36 to 109 +/- 33 mmHg; p less than 0.02), fractional shortening (20% +/- 4% to 17% +/- 9%; p less than 0.05) and peak positive dP/dt (1,006 +/- 224 to 921 +/- 287 mmHg; p less than 0.05). Measures of diastolic performance (peak negative dP/dt, the time constant of LV relaxation, the length of diastasis, and LV end diastolic stress) were not different between baseline beats and the strong beats; and only LV end-diastolic stress differed when baseline beats were compared to the weak beats. When the strong beats were compared to the weak beats during induced pulsus alternans, significant differences were observed in peak systolic pressure, peak positive dP/dt, and fractional shortening, but no differences in any measured diastolic parameter was observed. A slight difference was noted in the left ventricular end-diastolic diameters, with the weak beat consistently beginning at a slightly smaller diameter (61 +/- 13; mm vs 59 +/- 13; p less than 0.05). In summary, these data are consistent with an augmentation and deletion of intrinsic contractile forces in association with an alternation in preload on a beat-to-beat basis as best describing left ventricular performance during pulsus alternans. PMID- 3349515 TI - Coronary arteriographic findings in cocaine abuse-induced myocardial infarction. AB - A 31-year-old black man was admitted with an acute anterior myocardial infarction 20 minutes after IV cocaine abuse. Cardiac catheterization showed a totally occluded left anterior descending artery. Intracoronary and intravenous streptokinase resulted in thrombolysis: repeat angiography showed a normal anterior descending. PMID- 3349516 TI - Hemodynamic and cardiac metabolic changes during nicardipine-induced myocardial ischemia. AB - After 10 mg nicardipine IV a patient with stable angina developed chest pain and ST-segment depression accompanied by excessive tachycardia, low arterial blood pressure, and initially decreased coronary sinus blood flow. Measurements of arterial concentrations and cardiac exchanges of lactate, glucose, free fatty acids, glutamate, and alanine showed alterations indicative of severe ischemia. PMID- 3349517 TI - Hemodynamic effects of contrast media during coronary angiography: a comparison of three nonionic agents to Hypaque-76. AB - Coronary angiography with standard ionic contrast media is associated with marked alterations in cardiac hemodynamics because of the depressant effects of the contrast media on cardiac contractility. Nonionic contrast media have been reported to produce less hemodynamic alteration than standard ionic contrast media. However, there is no information on how one nonionic media compares to another. Thus we compared the hemodynamic effects of three nonionic contrast media, Iopamidol (IOP), Iohexol (IOH), and Ioversol (IOV) to each other as well as to the standard ionic contrast media Hypaque-76 (H76). In 20 closed-chest anesthetized dogs, we recorded the maximal change in left ventricular systolic pressure (LVSP), mean aortic pressure, left ventricular diastolic pressure (LVDP), and left ventricular dp/dt during 10-cc left main coronary artery injections of H76, IOP, IOH, and IOV. The mean aortic pressure and LVSP decreased 36 +/- 17 mm Hg and 46 +/- 21 mm Hg with H76 but only 5 +/- 5 mm Hg and 6 +/- 5 mm Hg with IOP, 5 +/- 4 mm Hg and 6 +/- 6 mm Hg with IOH, and 5 +/- 4 mm Hg and 7 +/- 6 mm Hg with IOV (P less than 0.001). The LVDP increased 6 +/- 5.0 mm Hg with H76 but only 0.2 +/- 0.5 mm Hg with IOP, 0.2 +/- 0.3 mm Hg with IOH, and 0.5 +/- 1.0 mm Hg with IOV (P less than 0.001). The LV dp/dt decreased 545 +/- 261 mm Hg/sec with H76 but increased 886 +/- 477 mm Hg/sec with IOP, 910 +/- 96 mm Hg/sec with IOH, and 473 +/- 335 mm Hg/sec with IOV (P less than 0.001). Whereas each nonionic agent produced significantly less hemodynamic abnormalities than H76, there was no significant difference between any of the nonionic agents on any hemodynamic parameter. Thus, as compared to H76, these nonionic contrast media produced only trivial alterations in hemodynamics and LV dp/dt. These agents may be preferable in patients with LV dysfunction. PMID- 3349518 TI - Clinical trial of the disposable transducer catheter. AB - We compared the intracardiac and intravascular pressures obtained by a conventional strain gauge transducer (CT) with a recently developed disposable high-fidelity transducer catheter (DT) during cardiac catheterization. CT was positioned at the patient's midchest level. The pressure measurements obtained by DT compared favorably with those of CT. Femoral arterial pressures by the two methods showed no statistical difference. Right heart pressures were similar using both transducers. However, right ventricular pressures by DT in five of eight patients were lower than that from CT. Higher pulmonary arterial pressures were noted in two of seven patients and higher pulmonary capillary wedge pressures were seen in four patients using DT compared to CT. None of these differences were of statistical significance. These pressure differences may be due to transducer position. Because the midchest position of CT does not precisely define the anatomic location of the cardiac chamber being studied, pressure measurements can be overestimated or underestimated. DT eliminates this problem, as well as overshooting and concern with air bubbles in the catheter system commonly associated with CT. Therefore DT may provide accurate hemodynamic measurements. It would appear to be useful regardless of patient position and may be useful in ambulatory hemodynamic determinations. PMID- 3349519 TI - Useful landmark in transseptal left heart catheterization. PMID- 3349520 TI - Injection of mitochondria into human cells leads to a rapid replacement of the endogenous mitochondrial DNA. AB - Isolated human mitochondria containing a mitochondrial DNA (mtDNA) coded chloramphenicol resistance marker were injected into cells from two different human sensitive cell lines, 143BTK- and HT1080-6TG, which had been partially depleted of their mtDNA by ethidium bromide treatment. On the basis of the available evidence concerning the tolerance of introduced volumes into mammalian cells, it is estimated that, on the average, less than one mitochondrion was introduced into each cell. Under selective conditions, the mitochondria became established in the recipient cells with a frequency greater than 2-3 x 10(-3). An analysis of multiple mtDNA and nuclear DNA polymorphisms revealed a rapid replacement of the resident mtDNA by the exogenous mtDNA. Six to ten weeks after microinjection, this replacement was complete in all but one of the HT1080-6TG transformants, and nearly complete in the majority of the 143BTK- transformants. The quantitative behavior of the mtDNA of the transformants at very early stages of selection strongly suggests that intracellular mtDNA selection played a crucial role in this replacement, with significant implications for mitochondrial genetics. PMID- 3349521 TI - Progression of rearrangements at T cell receptor beta and gamma gene loci during athymic differentiation of bone marrow cells in vitro. AB - A previously described in vitro system that supports T cell differentiation from bone marrow (BM) precursors was analyzed for T cell receptor gene rearrangement and expression. Cultured populations from days (d.) 0, 3, 6, and 12-13 were fused with BW5147. Only hybridomas from d.6 and d.12-13 bore BM-derived rearrangements. The rearrangement complexity was higher on d.12 than d.6 in that patterns consistent with D beta 1-J beta 1 and D beta 2-germ-line configurations decreased while V-D-J beta 2 and V gamma 2-J gamma 1 joining became dominant. Northern blots of d.13 BM cultures revealed gamma, alpha, and beta (1.0 and 1.3 kb) transcripts. Parallels between patterns in BM cultures and thymus ontogeny were recognized. PMID- 3349522 TI - Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. AB - Intercellular adhesion molecule 1 (ICAM-1) is a 90 kd inducible surface glycoprotein that promotes adhesion in immunological and inflammatory reactions. ICAM-1 is a ligand of lymphocyte function-associated antigen-1 (LFA-1), an alpha beta complex that is a member of the integrin family of cell-cell and cell-matrix receptors. ICAM-1 is encoded by an inducible 3.3 kb mRNA. The amino acid sequence specifies an integral membrane protein with an extracellular domain of 453 residues containing five immunoglobulin-like domains. Highest homology is found with neural cell adhesion molecule (NCAM) and myelin-associated glycoprotein (MAG), which also contain five Ig-like domains. NCAM and MAG are nervous system adhesion molecules, but unlike ICAM-1, NCAM is homophilic. The ICAM-1 and LFA-1 interaction is heterophilic and unusual in that it is between members of the immunoglobulin and intergrin families. Unlike other integrin ligands, ICAM-1 does not contain an RGD sequence. PMID- 3349523 TI - Stable expression of immunoglobulin gene V(D)J recombinase activity by gene transfer into 3T3 fibroblasts. AB - Using retroviral recombination substrates, we investigated the developmental stage of expression of V(D)J recombinase activity and the activation of recombinase activity in nonlymphoid cells. V(D)J recombinase activity was detected only in pre-B cells, but a DNA transfer protocol successfully activated V(D)J recombination in an NIH 3T3 cell line. The V(D)J recombinase activity was transferred in a second round of transfection and was then stably expressed in fibroblasts at a level comparable to that of a recombinationally active pre-B cell. It is likely that expression of a single, lymphoid-specific gene in a fibroblast is sufficient to confer V(D)J recombinase activity on that cell. PMID- 3349524 TI - Human CCAAT-binding proteins have heterologous subunits. AB - We have characterized three distinct proteins present in HeLa cell extracts that specifically recognize different subsets of transcriptional elements containing the pentanucleotide sequence CCAAT. One of these CCAAT-binding proteins, CP1, binds with high affinity to CCAAT elements present in the human alpha-globin promoter and the adenovirus major late promoter (MLP). A second protein, CP2, binds with high affinity to a CCAAT element present in the rat gamma-fibrinogen promoter. Finally, the third CCAAT-binding protein is nuclear factor I (NF-I), a cellular DNA-binding protein that binds to the adenovirus origin of replication and is required for the initiation of adenoviral replication. CP1, CP2, and NF-I are distinct activities in that each binds to its own recognition site with an affinity that is at least three orders of magnitude higher than that with which it binds to the recognition sites of the other two proteins. Surprisingly, CP1, CP2, and NF-I each appear to recognize their binding site with highest affinity as a multisubunit complex composed of heterologous subunits. In the case of CP1, two different types of subunits form a stable complex in the absence of a DNA binding site. Moreover, both subunits are present in the CP1-DNA complex. We thus propose the existence of a family of related multisubunit CCAAT-binding proteins that are composed of heterologous subunits. PMID- 3349525 TI - Isolation of a higher eukaryotic telomere from Arabidopsis thaliana. AB - We have developed a method for constructing genomic libraries enriched for telomeric DNA sequences, enabling the isolation of telomeres from higher eukaryotic organisms with large chromosomes. The method was used to clone telomeric DNA sequences from the flowering plant Arabidopsis thaliana. A. thaliana telomeres are composed primarily of tandemly repeated blocks of the sequence 5'-CCCTAAA-3' and are heterogeneous in size. Genomic sequences that cross-hybridize at high stringency with A. thaliana telomeric repeats are present in other higher plants. In Zea mays (corn), these cross-hybridizing sequences are located at the telomeres. In addition, the A. thaliana telomeric repeats cross hybridize at low stringency to genomic sequences located at the telomeres of human chromosomes. PMID- 3349527 TI - Complementation of the xeroderma pigmentosum DNA repair defect in cell-free extracts. AB - Soluble extracts from human lymphoid cell lines that perform repair synthesis on covalently closed circular DNA containing pyrimidine dimers or psoralen adducts are described. Short patches of nucleotides are introduced by excision repair of damaged DNA in an ATP-dependent reaction. Extracts from xeroderma pigmentosum cell lines fail to act on damaged circular DNA, but are proficient in repair synthesis of ultraviolet-irradiated DNA containing incisions generated by Micrococcus luteus pyrimidine dimer-DNA glycosylase. Repair is defective in extracts from all xeroderma pigmentosum cell lines investigated, representing the genetic complementation groups A, B, C, D, H, and V. Mixing of cell extracts of group A and C origin leads to reconstitution of the DNA repair activity. PMID- 3349526 TI - A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. AB - Tumor necrosis factor (TNF) is a monocyte-derived cytotoxin that has been implicated in tumor regression, septic shock, and cachexia. The mechanism by which TNF induces these different disease states is unclear. We have identified and characterized a novel, rapidly inducible cell surface cytotoxic integral transmembrane form of TNF. The existence and behavior of this novel form of TNF may explain the complex physiology of this molecule. We suggest that activated monocytes synthesize transmembrane TNF at the site of inflammation and kill their targets by either cell-to-cell contact or local release of the TNF secretory component. In contrast, septic shock and cachexia may result from either acute or chronic systemic activation of monocytes, resulting in the widespread release of TNF secretory component into the circulation of the affected individual. We further suggest that cell borne cytokines and cytotoxins may be the primary mediators of directed inflammatory responses. PMID- 3349528 TI - [Results of the surgical treatment of aortic coarctation in childhood]. PMID- 3349529 TI - [Colonoscopy in children and adults]. PMID- 3349530 TI - [Cardiovascular manifestations of the Williams-Beuren syndrome]. PMID- 3349532 TI - [New findings on the early psychological development in children--its importance for pediatric practice]. PMID- 3349531 TI - [A clinical case of pseudohypoaldosteronism]. PMID- 3349533 TI - [Pollinosis. 1]. PMID- 3349534 TI - [The physician and the computer. 13. Relations]. PMID- 3349535 TI - [Recreational-educational camps for children with diabetes]. PMID- 3349537 TI - [Pitfalls in substitute family care]. PMID- 3349536 TI - [Preventive care home visits in pediatric practice]. PMID- 3349538 TI - [Care of the neonate in the rooming-in system from the viewpoint of the mother]. PMID- 3349539 TI - [Neurologic aspects of Ehlers-Danlos syndrome in children]. PMID- 3349540 TI - [Problems in reaching the goal of "Health for All by the Year 2000"]. PMID- 3349541 TI - [Models of chronic noninfectious diseases]. PMID- 3349542 TI - [A cardiovascular program and its implementation under the specific conditions of the railway health care service]. PMID- 3349543 TI - [35 years of research in health education]. PMID- 3349544 TI - Airway assessment in obstetrical patients. PMID- 3349545 TI - Facial nerve paralysis following mask anaesthesia. PMID- 3349546 TI - Pseudo-embolism: Drum-Cartridge catheter. PMID- 3349548 TI - Factors influencing the presence of a leak around an endotracheal tube in patients with croup. PMID- 3349547 TI - Epinephrine test dose is not warranted for confirmation of intravascular migration of epidural catheter in a parturient. PMID- 3349549 TI - Gastric fluid volume and pH in elective inpatients. Part I: Coffee or orange juice versus overnight fast. AB - In order to assess the effect of preoperative oral fluids, with and without ranitidine, on gastric fluid volume and pH, 300 elective surgical inpatients, ASA physical status I or II, were randomly assigned to one of six groups. The three groups that received placebo are discussed in this paper, Part I, and the three that received ranitidine in Part II. Between two and three hours before the scheduled time of surgery patients received either 150 ml coffee (Group 1), or 150 ml orange juice (Group 2), while the control group continued their overnight fast (Group 3). No opiate or belladonna premedication was given. Immediately following induction of anaesthesia the residual gastric fluid was obtained by suction on a nasogastric tube and its volume and pH measured. Residual gastric fluid volumes showed no statistically significant differences among the groups (Group 1: 24.5 +/- 21.6 ml; Group 2: 23.7 +/- 18.4 ml; Group 3: 23.2 +/- 17.3 ml; p greater than 0.1). Values for pH among the groups were also similar (Group 1: 2.18 +/- 1.58; Group 2: 1.95 +/- 1.24; Group 3: 1.95 +/- 1.62; p greater than 0.1). PMID- 3349550 TI - Gastric fluid volume and pH in elective inpatients. Part II: Coffee or orange juice with ranitidine. AB - In order to assess the effect of preoperative oral fluids, with and without ranitidine, on gastric fluid volume and pH 300 elective surgical inpatients, ASA physical status I and II, were randomly allocated to one of six groups. The three ranitidine groups (Groups 4, 5, and 6) are discussed in this paper (Part II), and the three placebo groups (Groups 1, 2, and 3) in Part I. Between two and three hours before the scheduled time of surgery, patients received 150 ml coffee with oral ranitidine 150 mg (Group 4), 150 ml orange juice with oral ranitidine 150 mg (Group 5), or oral ranitidine alone (Group 6). No opiate or belladonna premedication was given. Immediately following induction of anaesthesia a # 18 Salem sump tube was passed and its position in the stomach confirmed by auscultation of insufflated air. The volume of residual gastric fluid, which was aspirated into a 60 ml syringe, was recorded, and its pH was measured. There were no statistically significant differences between groups with respect to volume (Group 4: 14.3 +/- 15.4; Group 5: 14.8 +/- 17.0; Group 6: 9.7 +/- 12.6 ml). The mean pH in all groups was greater than 5.40 (Group 4: 5.65 +/- 2.12; Group 5: 5.41 +/- 2.12; Group 6: 6.21 +/- 1.51). PMID- 3349551 TI - Effect of lumbar epidural anaesthesia on plasma cortisol levels in children. AB - The cortisol response to surgery was studied in two groups of children one to eight years old during the first 24 hours after lower abdominal or peripheral surgery. The children were randomly allocated to a control (C) group (n = 6) or an epidural (E) group (n = 7). In Group C, surgery was performed under general anaesthesia and postoperative pain relief was achieved by using non-narcotic analgesics only. In Group E, lumbar epidural anaesthesia was combined with light general anaesthesia and postoperative pain relief was achieved by intermittent doses of bupivacaine administered through an epidural catheter. Cortisol levels were assessed before surgery (C), at the end of surgery (H0), at the 3rd, 6th, 12th and 24th postoperative hours (H3, H6, H12, H24). In Group C, cortisol levels increased significantly at H0, H3 and H6, whereas in Group E, a significant decrease was observed at H0 and a significant increase at H12. Mean cortisol values at H0 and H24 were significantly lower in Group E, when compared with those measured in Group C. In Group E, all postoperative cortisol values remained within the normal range, despite the low level of sensory blockade achieved. This suggests that minimal doses of epidural bupivacaine are effective in decreasing the endocrine stress response to surgery in children. This could be of clinical relevance in high-risk children with poor nutritional status. In Group C, the cortisol response remained altered for a longer period of time. PMID- 3349552 TI - Comparison of circle absorber and Jackson-Rees systems for paediatric anaesthesia. AB - To evaluate effects of anaesthesia delivery systems on respiratory work in infants, we measured end-tidal PCO2 (PETCO2), transcutaneous PCO2 (PTcCO2) respiratory rate and arterial blood gases in infants (ages 0.2 to 23.8 months) anaesthetised with either a Jackson-Rees (n = 11) or paediatric circle absorber system (n = 15). Two hours after induction, with assisted ventilation there was no difference in PETCO2, PTcCO2, respiratory rate, pH or PaCO2 in infants anaesthetised with either system. In the laboratory, we measured inspiratory and expiratory resistances to breathing through each system at various tidal volumes and total gas flows into the circuit. These values were compared to resistances created by breathing through an appropriately sized endotracheal tube. Although there was lower resistance to ventilation through Jackson-Rees system, both systems had lower resistances for almost all flows tested than breathing through an endotracheal tube alone (p less than 0.05). The paediatric circle absorber system is an efficient apparatus for anaesthetising spontaneously breathing infants. PMID- 3349553 TI - Haemodynamic effects of induction of epidural analgesia in labour. AB - The effect of induction of epidural analgesia with 0.5 per cent bupivacaine on maternal haemodynamics was investigated in 21 patients with uncomplicated full term pregnancies in early labour. Stroke volume, heart rate, and cardiac output (SV, HR, and CO) were measured by transcutaneous aortovelography (TAV). Systolic, diastolic, and mean arterial blood pressures (SBP, DNP, and MAP) were measured by indirect automatic oscillometry. Measurements were made with the patient in the left lateral decubitus position before and after an intravenous bolus of 500 ml of lactated Ringer's solution preceding induction of epidural analgesia, and again 30 and 45 minutes after induction. The 500 ml bolus of lactated Ringer's solution did not prevent fall of CO and BP measured 30 minutes after induction, when there were statistically significant decreases in CO and cardiac index ( 10.2 and -10.6 per cent, p less than 0.05), and in SBP, DBP, and MAP (-9.7, 12.5, and -11.9 per cent, p less than 0.005, p less than 0.005 and p less than 0.01 respectively). At 45 minutes after induction, CO and cardiac index had returned to baseline values. Although the decreases in SDP and DBP persisted, the change in MAP was not statistically significant. PMID- 3349554 TI - Priming with anti-cholinesterases--the effect of different combinations of anti cholinesterases and different priming intervals. AB - This study was designed to investigate the effect of different combinations of neostigmine and edrophonium when administered in divided doses and the effect of different intervals (priming intervals) between the doses. Seventy-two patients divided into 12 groups (n = 6 in each) were included in the study. An initial dose of neostigmine 0.012 mg.kg-1 or edrophonium 0.2 mg.kg-1 was administered, followed at different priming intervals (1, 2 or 3 min) by either edrophonium 0.8 mg.kg-1 or neostigmine 0.048 mg.kg-1 for antagonism of atracurium-induced neuromuscular blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. Adequate reversal of neuromuscular block (train-of four ratio of 0.75) was achieved in all patients. Significant (p less than 0.05) acceleration of the recovery index (time taken for the twitch height to recover from 25 to 75 per cent of control) and reversal time (time taken from the end of injection of the priming dose until TOF ratio value had reached 0.75) was obtained in groups which received edrophonium-edrophonium combination. Recovery indices and reversal times were found to be significantly shorter (p less than 0.05) with a 1 min priming interval. In two additional groups of patients premedicated and anaesthetized as the others equipotent mixtures of the antagonists were administered as a single bolus dose. Reversal times were significantly longer (p less than 0.05) when compared to those given the same amounts of the combination but in divided doses with a 1 min priming interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349556 TI - Arterial oxygen saturation following premedication in children with cyanotic congenital heart disease. AB - To determine the effects of premedication on arterial oxygen saturation (SaO2) and heart rate (HR), 11 children (ages three to seven years) scheduled for elective repair of cyanotic congenital heart defects were studied. Patients were premedicated with oral or rectal pentobarbitone 2 mg.kg-1 90 minutes prior to induction of anaesthesia followed by intramuscular morphine 0.2 mg.kg-1 and atropine 0.02 mg.kg-1 60 minutes prior to induction. The SaO2 and HR of each child were monitored continuously using a Nellcor pulse oximeter during two 90 minute periods: a control period commencing 25.5 hours preoperatively (day 1) and a post premedication period commencing 1.5 hours preoperatively (day 2). Data were compared at time 0 (corresponding to the time of administration of pentobarbitone on day 2), 30 (corresponding to the administration of intramuscular morphine and atropine on day 2), 60 and 90 minutes (the latter corresponding to the time of induction on day 2) after the administration of pentobarbitone. There were no significant differences in SaO2 or HR between day 1 and day 2 at time 0, 60, and 90 minutes. The SaO2 (mean +/- SD) decreased significantly immediately following intramuscular premedication at time 30 minutes on day 2 (72.7 +/- 5.9 per cent) compared to the corresponding time on day 1 (83.9 +/- 2.9 per cent) (p less than 0.05). The duration of this desaturation was 2.5 +/- 1.9 minutes. Heart rate (mean +/- SD) increased from 109.2 +/- 21.3 beats.min-1 at time 30 minutes on day 1 to 142 +/- 20.4 beats.min 1 on day 2 (p less than 0.05). We conclude that administration of intramuscular premedication preceded by oral or rectal pentobarbitone causes transient arterial desaturation and tachycardia in children with cyanotic congenital heart disease. PMID- 3349555 TI - Priming with anti-cholinesterases--the effect of different priming doses of edrophonium. AB - The effect of different priming doses of edrophonium were studied in 77 patients divided into seven groups (n = 11 in each). Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I; controls) or in an initial dose of 0.05, 0.1, 0.15, 0.2, 0.25 or 0.3 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to VII respectively. Reversal was attempted at ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Increasing the size of the priming dose from 0.05 to 0.2 mg.kg-1 resulted in a stepwise increase (p less than 0.05) in recovery of T1 and train-of-four (TOF) ratio. Higher priming doses (0.25 and 0.3 mg.kg-1) were not associated with further improvement in T1 and TOF recovery. Reversal time, that is the time taken from the first injection of edrophonium until the TOF ratio value had reached 0.75 was significantly faster (p less than 0.01) following priming with edrophonium 0.2 mg.kg-1 (Group V) when compared to Groups I, II, III, IV and VI. Reversal times were also significantly faster in Groups IV and VI when compared to the control group. It is concluded that 0.2 mg.kg-1 appears to be the optimal priming dose for administration of edrophonium in divided doses. PMID- 3349557 TI - Acute hypothyroidism in a severely ill surgical patient. AB - A case of acute postoperative hypothyroidism in a 62-year old woman is presented. One month before emergency admission because of a perforated gastric ulcer the patient had normal thyroid function, despite removal of a thyroid adenoma 20 years earlier. Following surgery the patient developed circulatory instability, renal insufficiency, hypothermia and immeasurable concentrations of thyroxine (T4) and triiodothyronine (T3). Treatment with triiodothyronine was commenced but the patient died following an episode of severe hypotension. PMID- 3349558 TI - Anaesthetic implications of the trismus pseudocamptodactyly (Dutch-Kentucky or Hecht Beals) syndrome. AB - The trismus pseudocamptodactyly syndrome is a relatively rare, autosomal dominant condition first described in 1969. Affected patients classically present with two main features: limited excursion of the mandible and flexion deformity of the fingers that occurs with wrist extension (pseudocamptodactyly). Foot deformities and a shorter-than-normal stature may also be present. The underlying abnormality is short muscle tendon units, which prevent normal growth and development. We reviewed the anaesthetic experience in three paediatric patients with the trismus pseudocamptodactyly syndrome and the pertinent clinical findings in three other members of the same family, spanning three generations. Limited mandible excursion was present in all six cases, but was not obvious preoperatively in the patients because of its subtle presentation. All three cases were successfully managed using mask anaesthesia with spontaneous ventilation, avoiding muscle relaxants. Attempts to visualize the larynx under anaesthesia were unsuccessful in two cases. Blind nasotracheal intubation was successful in one patient. Postoperatively, there were no problems with the airway. PMID- 3349559 TI - Serum creatine kinase levels after succinylcholine in children with "muscle, eye and brain disease". AB - Four boys belonging to a group of children affected by a rare form of muscular dystrophy with eye and brain involvement, termed the "muscle, eye and brain disease" (MEB), were anaesthetized for various eye examinations and surgery. On some occasions succinylcholine was used during anaesthesia and the initially elevated serum creatine kinase (CK) values increased from a range of 122 to 1200 units.L-1 to a range of 4350 to 9690 units.L-1 22 hours after anaesthesia. CK values after anaesthesia without succinylcholine remained at the initially elevated levels. Rectal temperatures of the children were normal. These findings suggest that succinylcholine should be avoided in patients with MEB disease. PMID- 3349560 TI - Sodium thiosulfate fails to increase the therapeutic index of intravenously administered cis-diamminedichloroplatinum (II) in mice bearing murine and human tumors. AB - Intravenous (i.v.) administration of sodium thiosulfate reduces the toxicity of cis-diamminedichloroplatinum (II) (CDDP). This effect, which allows the use of increased CDDP doses, has been exploited clinically in the intraperitoneal (i.p.) treatment of intraabdominal tumors. Recently, attempts have been made to treat extraperitoneal tumors by concurrent i.v. administration of CDDP and sodium thiosulfate. We have tested this approach in mice bearing systemic L1210 leukemia, s.c. growing Lewis lung carcinoma, C3H mammary carcinoma, and a human sarcoma growing in athymic nude mice. In all cases the antitumor activity of CDDP was substantially reduced in a manner dependent on the thiosulfate dose. Increased doses of CDDP, permitted by reduced toxicity in the presence of thiosulfate, raised the antitumor activity. However, the latter did not exceed that obtained by much lower doses in the absence of thiosulfate. The present experiments in animal models thus fail to support the clinical use of CDDP given i.v. together with its antidote, sodium thiosulfate. PMID- 3349561 TI - Pharmacokinetics of Amonafide in dogs. AB - Amonafide, one of a series of imide derivatives of 1,8-naphthalic acid synthesized by Brana et al. has shown significant antitumor activity against a variety of experimental tumors, including L1210 leukemia and P388 leukemia. Along with the clinical trial at our institute, we have studied the disposition of Amonafide in dogs by HPLC and fluorometry. Six dogs received Amonafide i.v. at 5 mg/kg (100 mg/m2) over 15 min; three were sacrificed at 6 h, and three at 24 h. The initial plasma t1/2 of Amonafide was 2.4 +/- 0.4 min, the intermediate t1/2, 26.8 +/- 3.7 min, and the terminal t1/2, 21.7 +/- 4.0 h. The peak plasma concentration achieved was 6.3 +/- 1.7 micrograms/ml. The average apparent volume of distribution was 12.84 +/- 0.54 1/kg, and the total clearance was 0.56 +/- 0.16 1/kg/h. In 24 h, 9.5% +/- 0.2% of the administered dose was excreted in the urine as the parent drug, and 7.4% +/- 1.4% in the bile in 6 h. Amonafide penetrated the CSF readily and achieved the highest concentration 20-25 min after administration, which was 30% of the concurrent plasma level. Amonafide underwent extensive metabolism to at least three major metabolites and two or more minor metabolites. The alpha and beta plasma t1/2 of the major metabolite, an N-oxide derivative, were 24.8 min and 28.6 h, respectively. The 24-h cumulative urinary excretion was 1.4% of the injected dose, and the cumulative biliary excretion was 16.7% in 6 h. At autopsy 6 h after dosing, the liver contained the highest percentage (0.23% of administered dose) of unchanged Amonafide, followed by the stomach (0.11%), lung (0.04%), kidney (0.04%), and pancreas (0.03%). The rest of the major organs retained less than 0.02% of the Amonafide dose. One day after dosing, no detectable amount of Amonafide was found in any of these tissues, indicating that Amonafide appears to be extensively metabolized and not significantly retained in the dog. PMID- 3349562 TI - Pharmacokinetics of homoharringtonine in dogs. AB - We studied the pharmacokinetics and distribution of homoharringtonine (HHT), an antitumor alkaloid, in anesthetized dogs using chromatographic and radiochemical techniques. Uniformly tritiated HHT was administered i.v. to five dogs at doses of 0.05 to 0.34 mg/kg, 200 microCi per animal. Unchanged HHT disappeared in a triphasic manner from the plasma with an initial plasma t1/2 of 9.4 +/- 4.2 min, an intermediary t1/2 of 1.4 +/- 0.5 h, and a terminal t1/2 of 40.6 +/- 4.6 h. The plasma clearance was 114.0 +/- 20.1 ml/kg-1 h-1 and the steady-state volume of distribution was 6.2 +/- 0.7 1/kg. In 72 h, 40.1% +/- 4.0% of the administered radioactivity was excreted in the urine, 17.8% +/- 2.7% of which was unchanged HHT. HHT was metabolized extensively to one major and two minor metabolites. Biliary excretion of total radioactivity was 14.4% in 5 h, 2% of which was HHT. HHT concentration in the CSF was highest 4 h after drug administration, about 40% of the concentration in the concurrent plasma. At autopsy 5 h after dosing, the highest percentage of HHT was in the liver (7.4%), followed by the small intestine (2.5%), stomach (1.0%), pancreas (0.8%), kidneys (0.8%), and lungs (0.7%). The heart, spleen, large intestine, and brain each retained less than 0.5%. However, 24 h after dosing, 4% of the HHT still remained in the liver, 1% in the small intestine, and less than 1% in the other organs. HHT seems to be extensively metabolized in dogs and partially retained in the body. PMID- 3349563 TI - The cytolytic effect of L-2,4 diaminobutyric acid with malignant glioma cells and fibroblasts. AB - L-2,4-Diaminobutyric acid (DABA), an amino acid analogue, produced a cytolytic effect with a human glioma cell line, SKMG-1, and normal human fibroblasts. The concentrations of DABA necessary to reduce the cell count to 50% of control (LD50) following a 24-h incubation at 37 degrees C were 12.5 mM for the human fibroblasts and 20 mM for the glioma cell line. The concentrations of DABA necessary to produce an LD50 after a 48-h incubation at 37 degrees C were 10 mM for the human fibroblasts and 14 mM for the human glioma cell line. The cytolytic effect of DABA was similar in the absence or the presence of serum with the human glioma cell line. The cytolytic effect of 20 mM DABA was partially prevented by the presence of 5 mM methyl-AIB. DABA was not preferentially toxic to this human glioma cell line compared with normal fibroblasts. PMID- 3349564 TI - A sensitive high-performance liquid chromatographic assay for melphalan and its hydrolysis products in blood and plasma. AB - A sensitive high-performance liquid chromatographic assay has been developed for the measurement of the alkylating cytostatic drug melphalan (4-[bis(2 chloroethyl)amino]-L-phenyl-alanine, or L-phenylalanine-mustard, L-PAM) and its two hydrolysis products, monohydroxy melphalan (MOH) and dihydroxy melphalan (DOH). A reversed-phase phenyl column and a mobile phase consisting of acetonitrile/citrate buffer made possible an isocratic separation and quantification. N,N-[bis(2-hydroxy-ethyl)]toluidine has been synthesized as an internal standard structurally related to DOH. A new, accurate "kinetic" calibration procedure enabled us to determine even the concentration of the unstable MOH. The lower limit of quantification was 30 ng/ml for L-PAM and 20 ng/ml for both DOH and MOH with fluorescence detection. The use of this method is illustrated by some pharmacokinetic data in systemic and locoregional melphalan therapy. PMID- 3349565 TI - Accidental actinomycin D overdosage in man, a case report. AB - Although actinomycin D is a relatively old cytotoxic agent, relatively little is known about its toxicity in man in comparison with some of the newer cytotoxic agents that have been extensively investigated. We wish to describe a case where an overdose of actinomycin D was inadvertently administered. PMID- 3349566 TI - Metallothionein induction prevents toxic side effects of cisplatin and adriamycin used in combination. AB - The protective effects of metallothionein (MT) preinduction by bismuth subnitrate (BSN) against the renal toxicity of cis-diamminedichloroplatinum (cis-DDP), the cardiotoxicity of adriamycin (ADR), and the lethal and bone marrow toxicities of these drugs were observed in mice receiving cis-DDP and ADR simultaneously. Preinduction of MT biosynthesis by BSN, which is currently used as an antidiarrheal drug, did not affect the antitumor activities of the two drugs, suggesting that the beneficial effects of the preinduction of MT biosynthesis by BSN may be applicable for therapy involving cis-DDP and ADR, either alone or in combination. PMID- 3349567 TI - Avian thrombocyte thrombospondin. AB - A high molecular weight glycoprotein (450,000) was obtained from thrombin-treated duck thrombocytes by barium citrate adsorption technique followed by heparin agarose affinity chromatography. Amino acid composition (high number of acidic amino acids and cystine) as well as carbohydrate contents (1.3 per cent hexosamine, 0.9 per cent sialic acid and 1.5 per cent hexose) showed similarity to mammalian platelet thrombospondin. PMID- 3349568 TI - Chromatin organization in isolated nuclei: flow cytometric characterization employing forward and perpendicular light scatter. AB - Flow cytometric perpendicular and forward light scatters have been employed to evaluate whether the changes in chromatin organization due to ionic strength, Mg++ concentration and pH, visible in electron microscopy, can be monitored by flow cytometry. The average intensity of the perpendicular light scatter signal increased as nuclear chromatin became decondensed by lowering the ionic strength or releasing H1 histone at low pH values. These results indicate that flow cytometry signals and in particular the perpendicular light scatter allow the detection of the conformational transitions in chromatin and may therefore be useful for studying cell cycle associated morphological changes in isolated nuclei. PMID- 3349569 TI - Tightly-bound non-histone proteins in different nucleosome-like subpopulations from pig kidney chromatin. AB - By differential sucrose gradient centrifugation of pig kidney chromatin in the presence or absence of Na-EDTA and under varying ionic strength conditions, three nucleosome-like subpopulations with different buoyant densities can be obtained. These particles, on the basis of their histones and HMG protein pattern, of the 5 methylcytosine level of their DNA and of the RNA polymerase activity associated with them, can be considered as originating from chromatin fractions differently involved in gene expression. Two-dimensional electrophoresis of the tightly-bound non-histone proteins shows a distinct pattern for each subpopulation, such protein components being notably present in restricted numbers but in high amounts in the subpopulation which was apparently derived from condensed heterochromatin. PMID- 3349570 TI - Age-dependent changes in in vivo ethanol metabolism and in the activity of hepatic enzymes involved in ethanol oxidation and microsomal functions. AB - The study of the influence of the age of the animals (13 to 53 weeks) on the rate of ethanol metabolism in vivo and the total activity of liver alcohol dehydrogenase and microsomal ethanol oxidizing system showed a progressive decline with age. These effects were observed concomitantly with a diminution in the content of cytochrome P-450 and microsomal functions related to oxidative and free-radical mediated reactions, namely, NADPH oxidase activity, NADPH-dependent oxygen uptake and NADPH-or t-butyl hydroperoxide-induced chemiluminescence. It is concluded that ageing is accompanied by a diminution in the total oxidative activity of the liver tissue, which would explain the depression in basal and ethanol-induced lipid peroxidation found in the oldest group of rats studied. PMID- 3349571 TI - Pulmonary vasoconstrictor response to soluble fibrin in isolated lungs: possible role of thromboxane generation. AB - The blood coagulation system is activated regularly in severe forms of shock, polytrauma, and sepsis. Arising thrombin cleaves the fibrinopeptides A and B from fibrinogen, and it generates monomers of fibrin, which are initially kept in solution by the remaining excess fibrinogen. The effects of soluble fibrin (fibrin monomer/oligomer-fibrinogen complexes) and fibrinopeptides A and B were investigated in blood-free perfused, isolated rabbit lungs. Urea Tris buffer dissolved fibrin monomers were injected into the pulmonary artery in the presence of circulating excess fibrinogen. In doses above 5 mg, the monomers consistently provoked a sharp rise in pulmonary artery pressure, which was followed by an elevated pressure plateau. Changing to fresh perfusate devoid of soluble fibrin did not restore the pressure to baseline, and a second administration of the soluble fibrin caused a pressor response larger than the first. Only a modest increase in lung weight (less than 2 g) was observed, and lung inflation pressure was not altered. The pressor responses were accompanied by a rapid release of thromboxane A2 and a more delayed release of prostaglandin I2 into the perfusion fluid. A significant correlation between the height of the fibrin-induced pressure rise and the amount of thromboxane release was noted. Inhibition of cyclooxygenase (indomethacin) suppressed the generation of both prostanoids, whereas inhibition of thromboxane synthetase (OKY-046 and imidazole) selectively blocked the liberation of thromboxane. All three inhibitors caused an immediate decline in pulmonary artery pressure, which had been previously elevated due to administration of soluble fibrin, and markedly reduced the pressor response evoked by a subsequent fibrin application in the same lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349572 TI - Monohydroxyeicosatetraenoic acids (5-HETE and 15-HETE) induce pulmonary vasoconstriction and edema. AB - 5-, 15-, and 12-HETE (monohydroxyeicosatetraenoic acids) are products of the lipoxygenation of arachidonic acid. We investigated their role as possible mediators of pulmonary vasoactivity and pulmonary edema. Pulmonary artery pressure (Ppa), capillary pressure (Pcap), the change in lung wet weight (delta wt) from baseline, and capillary filtration coefficient (Kf) (as a measure of vascular permeability) were determined following an intravenous injection of each mono-HETE in lungs perfused at constant flow with either a phosphate-buffered Ringer's-albumin solution (PBR) or diluted blood. Injection of 2 micrograms of each compound into the pulmonary artery of lungs perfused with either PBR or diluted blood did not produce any effect. However, in PBR-perfused lungs, 4 micrograms 15-HETE induced increases in Ppa, Pcap, and lung wet weight (p less than 0.05), which were greater than the increases observed after 4 micrograms 5 HETE. Kf increased following both 5- and 15-HETE. The pulmonary vasoconstrictor and edemagenic responses were attenuated by increasing perfusate albumin concentration from 0.5 to 1.5 g%. In contrast, 12-HETE (4 micrograms) had no effect on these parameters. In blood-perfused lungs, the pulmonary vascular responses to all HETE compounds (4 micrograms) were attenuated. In both Ringer's albumin-perfused and blood-perfused lungs, the relative magnitude of the hemodynamic and fluid filtration responses to each mono-HETE were as follows: 15 HETE greater than 5-HETE greater than 12-HETE. In conclusion, the pulmonary vasoconstrictor and edemagenic effects of 5- and 15-HETE occur independently of blood-formed elements. 15-HETE causes greater pulmonary vasoconstriction and edema than 5-HETE. Both 5- and 15-HETE induce pulmonary edema, probably as a result of increased lung vascular permeability. The results indicate that 5- and 15-HETE are potent pulmonary inflammatory mediators. PMID- 3349573 TI - Quantification in vivo of increased LDL content and rate of LDL degradation in normal rabbit aorta occurring at sites susceptible to early atherosclerotic lesions. AB - While the exact mechanisms that initiate atherosclerotic lesions are unknown, considerable evidence supports a role for low density lipoprotein (LDL). We investigated whether in the normal rabbit, LDL metabolism in areas of aorta that are destined to become lesioned during cholesterol feeding differed from the metabolism in adjacent lesion-resistant aorta. These studies took advantage of the predictable pattern of early atherosclerotic lesions in the cholesterol-fed rabbit. Early lesions occur diffusely in the aortic arch and ascending aorta and distal to branch orifices in the abdominal aorta and the descending thoracic aorta. Arterial rates of irreversible degradation of LDL and concentrations of intact LDL were measured in susceptible and resistant sites with homologous doubly labeled LDL. LDL was labeled directly with 131I and with 125I-tyramine cellobiose. The latter label provides a highly sensitive means to determine the sites and rates of lipoprotein degradation in vivo. The arterial concentration of intact LDL in the lesion-prone aortic arch was 3.12 +/- 0.45 micrograms LDL cholesterol/g (n = 14), 3.6 +/- 0.69 times that in the relatively lesion resistant descending thoracic aorta (p less than 0.001). The rate of LDL degradation in the aortic arch was 3.14 +/- 0.41 micrograms LDL cholesterol/g/day, 2.14 +/- 0.24 times that in the descending thoracic aorta (p less than 0.001). In the abdominal aorta, the LDL (per gram wet weight) concentration and degradation rate (per square centimeter surface area) at branch sites exceeded that at nonbranch sites by 88 +/- 11% (p less than 0.001) and by 61 +/- 8% (p less than 0.001), respectively. These data provide evidence that in the normal rabbit, which does not develop atherosclerotic lesions, focal elevations of arterial LDL degradation rate and concentrations of intact LDL occur at sites that first develop atherosclerotic lesions in the hypercholesterolemic animal. These differences in LDL metabolism may be linked causally to the propensity to develop atherosclerotic lesions at these sites. PMID- 3349574 TI - Technique for measuring regional two-dimensional finite strains in canine left ventricle. AB - We developed a technique to measure regional two-dimensional deformations in the myocardium. Three piezoelectric crystals were implanted in a triangular array in the left ventricular anterior midwall in six anesthetized dogs. Each crystal was used in a dual function, to both transmit and receive ultrasonic signals from the other two crystals. In this manner, the three segment lengths of the crystal triangle throughout the cardiac cycle were simultaneously recorded. The orientation of the crystal triangle with reference to the left ventricular long and minor axes was determined. The orientation and three segment lengths of the crystal triangle were used to calculate the circumferential strain E11, the longitudinal strain E22, the in-plane shear strain E12, and the mutually perpendicular principal strains E1 and E2. Also, the orientation of the first principal direction or the in-plane angle was determined, which was defined as the angle between the first principal direction (E1) and the circumferential direction (0 degree). This information fully describes the regional two dimensional myocardial deformations. This technique was applied to measure regional myocardial deformations at three different left ventricular end diastolic pressures (LVEDP) of 2 +/- 1 (mean +/- SD), 8 +/- 1, and 17 +/- 2 mm Hg. The first principal direction at end-systole was oriented away from the circumferential direction at low LVEDP (-43 +/- 21 degrees) but became progressively closer in each animal to the circumferential direction as LVEDP increased to mid (-26 +/- 18 degrees) and high (-14 +/- 13 degrees) levels. The end-systolic ratio E11/E1 was 0.6 +/- 0.2 at low LVEDP, but increased toward unity in each animal to 0.9 +/- 0.1 at mid and high LVEDP. Thus, at low LVEDP, the greatest systolic deformation occurred in a direction different from the circumferential orientation. Therefore, circumferential strain measurements (E11) significantly underestimated the greatest systolic deformation (E1). However, as LVEDP increased, the first principal direction rotated closer toward the circumferential orientation, and circumferential strain measurements adequately estimated the greatest systolic deformation. Nevertheless, the presence of significant amounts of shortening along either the longitudinal (E22) or the second principal direction (E2) in the midwall necessitated the use of the two dimensional method. The change in end-diastolic configuration as LVEDP increased from 1 +/- 1 to 16 +/- 1 mm Hg was also examined. Unlike the end-systolic data, the end-diastolic first principal direction did not deviate significantly from the circumferential direction at any LVEDP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3349575 TI - Reactivity of isolated porcine coronary resistance arteries to cholinergic and adrenergic drugs and transmural pressure changes. AB - The reactivity of porcine intramyocardial resistance arteries (223 +/- 7 micron i.d., n = 30) was investigated with a pressurized in vitro preparation. Diameter changes in response to acetylcholine and to adrenergic drugs and dynamic changes in transmural pressure changes were investigated. Acetylcholine produced concentration-dependent constrictions, causing maximal reductions of 71 +/- 3% in lumen diameter, with EC50 values averaging 1.9 X 10(-7) M (n = 7). These responses were inhibited by atropine (10(-7) M) and therefore were mediated by muscarinic receptors. In addition, acetylcholine did not elicit relaxation in nine out of 10 vessels precontracted with U46619 (10(-7) M). Norepinephrine and epinephrine never produced constrictions (n = 6) even in the presence of propranolol (10(-6) M). Both norepinephrine and isoproterenol caused dose dependent relaxations in acetylcholine-precontracted vessels, with IC50 values of 8.2 X 10(-7) M (n = 5) and 6.6 X 10(-8) M (n = 6), respectively. These relaxations were suppressed by propranolol. Between transmural pressures of 10 and 90 mm Hg, there was no intrinsic myogenic tone (n = 7). In addition, the vessels responded only passively to sudden pressure changes of 40 mm Hg. In all vessels, the functional integrity of the endothelium was verified by relaxations to substance P (10(-8) M) and/or bradykinin (10(-8) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349577 TI - Role of adenosine in coronary vasodilation during exercise. AB - This study examined the hypothesis that increases in myocardial blood flow during exercise are mediated by adenosine-induced coronary vasodilation. Active hyperemia associated with graded treadmill exercise and coronary reactive hyperemia were examined in chronically instrumented awake dogs during control conditions, after intracoronary infusion of adenosine deaminase (5 units/kg/min for 10 minutes), and after adenosine receptor blockade with 8-phenyltheophylline. Both adenosine deaminase and 8-phenyltheophylline caused a rightward shift of the dose-response curve to intracoronary adenosine; 8-phenyltheophylline was significantly more potent than adenosine deaminase. Adenosine deaminase caused a 33 +/- 7 to 39 +/- 3% decrease in reactive hyperemia blood flow following coronary occlusions of 5-20 seconds duration, respectively, while 8 phenyltheophylline produced a 40 +/- 6 to 62 +/- 8% decrease in reactive hyperemia. Increasing myocardial oxygen consumption during treadmill exercise was associated with progressive increase of coronary blood flow. Neither adenosine deaminase nor 8-phenyltheophylline attenuated the increase in coronary blood flow or the decrease of coronary vascular resistance during exercise. Neither agent altered the relation between myocardial oxygen consumption and coronary blood flow. Thus, although both adenosine deaminase and 8-phenyltheophylline antagonized coronary vasodilation in response to exogenous adenosine and blunted coronary reactive hyperemia, neither agent impaired coronary vasodilation associated with increased myocardial oxygen requirements produced by exercise. These findings fail to support a substantial role for adenosine in mediating coronary vasodilation during exercise. PMID- 3349576 TI - Transmural variation in autoregulation of right ventricular blood flow. AB - We examined transmurally the right coronary autoregulatory flow response to varied perfusion pressures in 11 anesthetized, open-chest dogs. Right coronary artery flow was measured electromagnetically, and its transmural distribution was defined with 15-micron radioactive microspheres. Heart rate, mean aortic blood pressure, right ventricular systolic pressure, end-diastolic pressure, and dP/dtmax were constant. At 100 mm Hg, subepicardial flow averaged 0.48 +/- 0.04 ml/min/g, and subendocardial flow averaged 0.56 +/- 0.05 ml/min/g. In contrast to the left coronary circulation, right coronary hypotension did not cause preferential subendocardial ischemia. As right coronary perfusion pressure was decreased from 100 to 40 mm Hg in five dogs, subepicardial and subendocardial flows were reduced similarly by 35-36%. As right coronary perfusion pressure was elevated from 100 to 150 mm Hg in six dogs, right ventricular subepicardial blood flow increased by 31%, whereas subendocardial blood flow increased by 70%. Right ventricular subendocardial-to-subepicardial flow ratios averaged 1.15-1.20 for perfusion pressures of 40 to 120 mm Hg, and they increased to 1.36 +/- 0.05 at 150 mm Hg. Right coronary artery autoregulatory closed-loop gain averaged 0.47 +/ 0.06 between 70 and 100 mm Hg and was greater than zero from 40 to 120 mm Hg. Between 120 and 150 mm Hg, gain fell to -0.15 +/- 0.10. Regional gain varied from 0.59 +/- 0.10 to 0.44 +/- 0.08 in subepicardium as pressure was decreased from 100 to 40 mm Hg. Subendocardial gains were similar to subepicardial gains over this pressure range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349578 TI - Role of sarcoplasmic reticulum in arterial contraction: comparison of ryanodines's effect in a conduit and a muscular artery. AB - Ryanodine interferes with sarcoplasmic reticulum function in various types of muscle; in vascular smooth muscle, it can inhibit contractions that depend on sarcoplasmic reticulum calcium release, probably by depleting the sarcoplasmic reticulum calcium store. We tested ryanodine and calcium channel blockers (verapamil, diltiazem, and nitrendipine) on small rings of rat thoracic aorta (RA) and bovine tail artery (BTA) to determine the relative contributions of sarcoplasmic reticulum calcium release and gated calcium entry to contractions induced by norepinephrine, caffeine, and 100 mM K depolarization. Ryanodine blocked caffeine contractions in both tissues and attenuated norepinephrine responses (by 52% in RA, 14% in BTA) but minimally altered potassium contractions. Calcium channel blockers almost completely abolished potassium contractions and reduced norepinephrine contractions (by 45% in RA, 82% in BTA) but hardly affected caffeine responses. The blocking effects of ryanodine and calcium channel antagonists on the norepinephrine responses were additive. Ryanodine had no effect on baseline tension in the standard media; however, when calcium extrusion via Na-Ca exchange was inhibited by low external sodium (0 calcium, low-sodium solution), tension increased progressively after introduction of ryanodine. This indicates that the sarcoplasmic reticulum calcium released by ryanodine then accumulated in the cytosol and activated contraction; restoration of external sodium caused prompt relaxation. The smaller effects of caffeine and ryanodine in BTA indicate that sarcoplasmic reticulum plays a less important role in calcium control in this tissue, with gated calcium entry dominating. These functional findings are correlated with electron-microscopic evidence that BTA has about 60% less sarcoplasmic reticulum than does RA. Ryanodine appears to be a useful tool for determining the functional relevance of sarcoplasmic reticulum for contraction in different arterial smooth muscles. PMID- 3349579 TI - Comments on "Load regulation of the properties of adult feline cardiocytes: the role of substrate adhesion."Circ Res 1986;58:692-705. PMID- 3349580 TI - Relationship between the 12-lead electrocardiogram during ventricular tachycardia and endocardial site of origin in patients with coronary artery disease. AB - Previous studies in patients with sustained ventricular tachycardia (VT) have demonstrated the efficacy of surgical and catheter-mediated ablative procedures based on activation mapping during VT. Since extensive preoperative or intraoperative mapping may be impractical due to time constraints or patient intolerance, we sought to define characteristics of the 12-lead electrocardiogram (ECG) during VT that could suggest a particular endocardial region of origin and thus facilitate mapping studies. Endocardial mapping was performed during 182 VTs in 108 patients with prior myocardial infarction of either the anterior or inferior wall. Endocardial sites of origin (sites from which greater than or equal to 40 msec of presystolic electrical activity was consistently recorded) were identified with use of catheter (154 VTs) or intraoperative (85 VTs) activation mapping (both methods used in 57 Vts). Twelve-lead ECGs obtained during these VTs were characterized by four features: location of infarction, bundle branch block type configuration, quadrant of QRS axis, and precordial R wave progression pattern. A specific combination of these four features was associated with a particular endocardial region containing the mapped site of origin in 87 VTs (48% of total). An association (greater than or equal to 70% positive predictive accuracy) was more likely to be found in the presence of left, as opposed to right, bundle branch block type patterns (53/73 [73%] vs 34/109 [31%]; p less than .001) and in the presence of VT related to inferior, as opposed to anterior, infarction (40/54 [74%] vs 47/128 [37%]; p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349581 TI - Comparative clinical and electrophysiologic effects of adenosine triphosphate and verapamil on paroxysmal reciprocating junctional tachycardia. AB - The efficacy, electrophysiologic effects, and side effects of adenosine triphosphate (ATP) and verapamil in the short-term management of paroxysmal reciprocating junctional tachycardia (PRJT) were compared in 20 patients. All patients had inducible sustained PRJT during control electrophysiologic study. Fourteen patients had PRJT involving a retrograde accessory pathway, and six patients had atrioventricular (AV) nodal reentrant tachycardia ("slow-fast" type). ATP, which has a very short half-life, was first administered (10 mg iv over 1 sec) during sustained PRJT. If PRJT did not terminate within 2 min, a bolus of 20 mg ATP was given. Verapamil (5 mg iv over 15 sec) was subsequently administered during sustained PRJT, and if the latter did not terminate within 3 min another bolus of 5 mg verapamil was given. The cycle lengths of PRJT before administration of 10 or 20 mg ATP and 5 mg verapamil were similar. The 10 mg dose of ATP terminated PRJT in 17 of the 20 patients, and 20 mg ATP was required to terminate PRJT in the three remaining patients. The 5 mg dose of verapamil terminated PRJT in 15 patients, whereas an additional bolus of 5 mg terminated PRJT in one of the remaining five patients. The overall efficacy of ATP (20/20, 100%) was significantly greater than that of verapamil (16/20, 80%) (p less than .05); however, there was no significant difference between the conversion rate of PRJT after administration of 10 mg ATP (17/20) and 5 mg verapamil (15/20). ATP terminated PRJT more quickly than verapamil (mean 24 sec vs mean 51 sec; p less than .01). Termination of PRJT by either ATP or verapamil was mainly related to a block in the AV node in patients with accessory pathways and to a block in the antegrade slow pathway in patients with AV nodal reentry. Cycle length alternans before termination of tachycardia was observed more frequently after verapamil than after ATP (7/16 vs 1/20; p less than .01). The total incidence of transient second-degree AV nodal block and various cardiac supraventricular and ventricular arrhythmias was higher after termination of PRJT by ATP than after verapamil (17/20 vs 5/16; p less than .001). A higher incidence of transient but frequently uncomfortable noncardiac side effects was observed after ATP. We conclude that ATP (10 to 20 mg) is more effective and more rapid than verapamil (5 or 5 + 5 mg) in terminating PRJT but results in a higher incidence of cardiac and noncardiac side effects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3349582 TI - Electrogram patterns predicting successful catheter ablation of ventricular tachycardia. AB - Ventricular tachycardia in patients with remote myocardial infarction is thought to be due to reentry. To improve the efficacy of catheter ablation, we sought to identify electrograms identifying essential components of the reentrant circuit. In this study we compared the efficacy of shocks delivered at sites of early ventricular activation during tachycardia (presumably exit sites from the reentrant circuit) with that of shocks delivered at sites recording mid-diastolic potentials that were not continuous with the main ventricular potential recorded during the QRS complex, but that always remained associated with the tachycardia during initiation, termination, and resetting with extrastimuli (presumably activation of a segment of the slowly conducting region of the reentrant circuit). A total of 20 attempts was made to ablate 14 monomorphic ventricular tachycardias in 10 patients with remote myocardial infarction with use of one to five shocks of 50 to 370 J (200 J in 70%). All seven tachycardias in which isolated mid-diastolic potentials were targeted were successfully ablated, although one required a second attempt. Twelve attempts were made to ablate seven tachycardias by delivering shocks at sites of early activation during tachycardia when mid-diastolic potentials were not identified. Only three attempts (25%) were successful. Activation preceded the QRS complex by 60, 85, and 120 msec in the three successful attempts and by 20 to 110 msec (median 55 msec) in the nine unsuccessful attempts. For the total 20 attempts, there was no significant difference between successful and nonsuccessful ablation in the number of shocks or total energy delivered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349583 TI - Mitral valve prolapse in patients with prior rheumatic fever. AB - It is known that rheumatic heart disease frequently results in isolated mitral regurgitation without concomitant mitral stenosis, especially in countries with a high prevalence of rheumatic fever. However, more recent surgical pathologic data also have demonstrated a high incidence of mitral valve prolapse in cases of rheumatic heart disease, which suggests that rheumatic fever may be a cause of mitral valve prolapse. To determine whether this association of mitral valve prolapse and rheumatic heart disease is present in a stable clinic population, we studied 30 patients who had an apical systolic murmur and a well-documented history of rheumatic fever with dynamic auscultation, two-dimensional echocardiography, and pulsed Doppler examinations. Twenty of the 30 patients (67%) had findings on physical examination consistent with isolated mitral regurgitation and 25 patients (84%) had mitral regurgitation by Doppler examination. Echocardiography demonstrated mitral valve prolapse in 24 patients (80%), whereas only one of the total study group had echocardiographic findings consistent with mitral stenosis. We conclude that (1) the presence of an isolated systolic murmur in patients with a history of rheumatic fever frequently represents pure mitral regurgitation secondary to mitral valve prolapse and (2) postinflammatory changes in valvular tissue resulting from rheumatic fever may be the etiology of mitral valve prolapse in these patients. PMID- 3349585 TI - ST segment elevation with exercise: a marker for poor ventricular function and poor prognosis. Coronary Artery Surgery Study (CASS) confirmation of Seattle Heart Watch results. AB - The functional and prognostic significance of exercise-induced ST elevation (by computer averaging) in ambulatory patients with coronary heart disease was recently reported for 181 patients in the Seattle Heart Watch (SHW). To further evaluate this, 3050 approximately similar patients enrolled in CASS were analyzed with respect to initial findings, survival, and incidence of secondary coronary events over the next 6 years. The ST elevation responses in CASS patients were classified by visual interpretation of 1 mm or more, whereas the SHW patients were identified by voltage greater than 0 mV. Accordingly, prevalence of exercise induced ST elevation was lower in CASS patients, but they had greater frequencies of prior myocardial infarction and left ventricular enlargement and dysfunction. The poor survival was similar in the subgroup with ST elevation during exercise and recovery in CASS and SHW. Although not an independent predictor when invasive variables are known, ST elevation emerges as a useful predictor when exercise testing is performed before diagnostic invasive studies. PMID- 3349584 TI - Myocardial oxygen consumption, oxygen supply/demand heterogeneity, and microvascular patency in regionally stunned myocardium. AB - Although oxygen consumption closely parallels mechanical work in the normal heart, previous studies have found that stunned myocardium may have normal or even increased oxygen consumption despite depressed function. In this study we used microspectrophotometry to measure the oxygen saturations within arteries and veins of less than 100 micron diameter in quick-frozen biopsy samples from normal and regionally stunned myocardium of 10 open-chest anesthetized dogs. Regional myocardial blood flow, measured by radioactive microspheres, was similar in stunned and normal regions, as was mean arteriolar oxygen saturation. However, mean venous oxygen saturation was lower in the stunned region (epicardium 38.0% vs 43.8%, p less than .02; endocardium 36.2% vs 39.5%, p = .12), indicating increased oxygen extraction and consumption, despite a marked reduction in mean systolic segmental shortening from 14.4% to 0.5%. In addition, there was greater vein-to-vein heterogeneity of oxygen saturation in the stunned region, with an excess of veins having low saturations (statistically significant in epicardium, nonsignificant trend in endocardium). Microvascular injections studies with Microfil or drafting ink revealed filling of over 95% of arterioles and 85% of capillaries in the stunned region, similar to the findings in the normal region. Our results are consistent with an inefficient transfer of energy into myocyte contraction or an increased use of energy for noncontractile activities in stunned myocardium. In addition, the finding of increased heterogeneity of oxygen extraction suggests that the injury to stunned myocardium may not be uniform to all contractile elements, but instead may be focally and irregularly distributed. PMID- 3349586 TI - The effects of a critical stenosis on myocardial blood flow, ventricular function, and infarct size after coronary reperfusion. AB - Immediate percutaneous transluminal coronary angioplasty has been advocated for patients with a residual stenosis after coronary thrombolysis because of the possibility that the residual stenosis may restrict reflow and thereby increase infarct size. Because there are few experimental data bearing on this issue, we measured left ventricular function, myocardial blood flow, and infarct size in 20 anesthetized open-chest dogs during 2 hr of left circumflex occlusion and 4 hr of reperfusion. Ten animals were reperfused through a critical stenosis of the left circumflex artery (critical stenosis group) and the remaining 10 animals underwent full reperfusion without stenosis (control group). In both groups, a comparable degree of echocardiographic systolic wall thinning was present during occlusion and partial recovery of global and regional left ventricular function in the two groups. Subendocardial blood flow was decreased in the critical stenosis group relative to the control group at 5 min after reperfusion (0.52 +/- 0.16 ml/min/g in the critical stenosis group vs 1.55 +/- 0.32 ml/min/g in the control group, p less than .05) but not at 4 hr after reperfusion, when a reduced reflow response was seen in both groups. No differences in subepicardial blood flow were seen in the two groups of animals. Infarct size was slightly greater in the critical stenosis group than the control group, but this difference was not statistically significant (infarct/risk area ratio: 55.5 +/- 7.8% in the critical stenosis group vs 39.4 +/- 9.7% in the control group, p = .21). A close inverse exponential relationship was seen between infarct size/risk area ratio and subendocardial blood flow during occlusion (r = .89, p = .001). Two control animals had high levels of subendocardial collateral flow (greater than 0.2 ml/min/g); when these animals were excluded from analysis, differences in the infarct size/risk area ratio in the control and critical stenosis groups were less striking: (55.5 +/- 7.8% in the critical stenosis group vs 48.4 +/- 9.6% in the control group). Thus, the presence of a critical stenosis results in restriction of hyperemic blood flow to the subendocardium after reperfusion but does not influence infarct size or early left ventricular functional recovery. PMID- 3349587 TI - Assessment of thallium-201 redistribution versus glucose uptake as predictors of viability after coronary occlusion and reperfusion. AB - Both 201Tl redistribution and persistent glucose uptake have been proposed as markers of viability after reperfusion. In the present study, they have been compared in the same open-chest canine preparation of occlusion and reperfusion. Ten fasting dogs were subjected to 2 hr of left anterior descending coronary artery occlusion and 4 hr of reperfusion. Myocardial blood flow was determined by a microsphere technique 100 min after occlusion and 3 hr after reperfusion. 201Tl was injected intravenously 20 min before reperfusion. Serial biopsy samples were obtained from ischemic and normal areas. 18F-2-deoxyglucose, a tracer of exogenous glucose uptake, was injected 3 hr after reperfusion. Thirty minutes before the animals were killed, simultaneous blood samples were taken from the femoral artery and the regional coronary veins draining the reperfused and the remote areas. Dogs were killed 4 hr after reperfusion was established. Area at risk was assessed by dye injection in vivo and area of necrosis by triphenyl tetrazolium chloride (TTC) staining, with confirmation by electron microscopy. Immediately after death, endocardial and epicardial samples were taken from regions characterized as risk regions, areas of necrosis, areas of patchy necrosis, and normal areas. These samples were counted in a scintillation well counter. Four hours after reperfusion, in ischemic myocardium (TTC positive) the relative 201Tl gradient between ischemic and normal regions was 26 +/- 13%, whereas in necrotic samples, this gradient was 71 +/- 26%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349588 TI - Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs. AB - To gain insight into the differences in antiarrhythmic potential of right vs left stellate ganglionectomy, 72 dogs were randomized to either unilateral stellectomy or second intercostal space thoracotomy and left circumflex coronary arteriovenous pedicle occlusion was performed, without vagotomy, a mean of 8 weeks later under anesthesia. The type and timing of ventricular ectopic beats, including both nonsustained and sustained ventricular tachycardia and ventricular fibrillation, were investigated. Several covariates, including postischemic electrocardiographic changes, were considered. Both right and left stellate ganglionectomy reduced the incidence of early (0 to 10 min) (p = .004 and p = .001, respectively) and total (0 to 60 min) (p = .009 and p = .008, respectively) ischemia-induced ventricular fibrillation, and improved outcome (p = .0013 and p = .0012, respectively). Early sustained ventricular tachycardia was similarly reduced (p = .02) in both stellectomized groups. By contrast, neither the type nor the time distribution of the other forms of ventricular arrhythmias differed significantly among the randomized groups. The multivariate Cox's regression model showed that ST segment elevation at 3 min postocclusion, unilateral stellate ganglionectomy (either right or left), sex, and weight were significant independent predictors of the incidence of ventricular fibrillation during the occlusion period. Lower ST segment elevation and reduced incidence of sustained ventricular tachycardia in the early postischemic period might explain improved outcome in stellectomized dogs by Cox analysis. The side of intervention (either stellectomy or sham operation) did not influence survival; however, left-sided interventions were more effective than right-sided ones. These results confirm the previously reported antifibrillatory effect of left and indicate like effects of right stellate ganglionectomy in a randomized experimental study. PMID- 3349589 TI - Allergic reactions to vespids: comparison of sensitivities to two species in a Mediterranean area. AB - We have studied a group of twenty-seven patients who suffer allergic reactions to vespids stings. Specific IgE antibodies to venom extracts from Polistes gallicus and Vespula germanica were measured by RAST, and the crossreactivity between the two venoms was compared using the RAST inhibition technique. We concluded that, in southern Spain, sensitization to P. gallicus was more prevalent than that to V. germanica, with 44% of the subjects in this study reacting to P. gallicus compared with 33% to V. germanica. However, there was a considerable degree of crossreactivity between the two species. It is evident that Polistes is an important species in this area; however, both in Spain and other Mediterranean countries, V. germanica venom is used almost exclusively for diagnosis and immunotherapy. PMID- 3349590 TI - Symptom scores as measures of the severity of rhinitis. AB - Methodological aspects of subjective symptom ratings were investigated in 103 symptomatic rhinitis patients. The patient's own overall rating registered on a visual analogue scale was compared with a summed symptom score calculated from ratings of sneezing, rhinorrhea and congestion. A significant correlation, but not complete correspondence, was found in patients with untreated rhinitis during the birch pollen season and after challenges with birch pollen or histamine. Comparisons between the overall rating and scores for individual symptoms gave lower degrees of correlation or non-significant correlations. When twenty-five patients were treated with an intranasal corticosteroid during the pollen season, both the overall rating and the summed symptom score decreased significantly. The changes in the two ratings for each patient showed a moderate correlation. The patients' ratings of rhinorrhea correlated with an approximate measure of the volume of secretion after pollen challenge but not during the pollen season or after histamine challenge. It is recommended on the basis of these findings that, for measuring the severity of rhinitis, scores indicating the course of individual symptoms should not be combined into a summed score, but that the patient's overall rating of the condition should be used. Scores for individual symptoms can be used to draw more detailed conclusions about nasal pathophysiological features and about qualitative disimilarities between different modes of therapy. PMID- 3349592 TI - Skin testing with extracts of fungal species derived from the homes of allergy clinic patients in Toronto, Canada. AB - Airborne fungi in the homes of patients with allergic rhinitis or asthma, from a Toronto Allergy Clinic population, were isolated, quantified and identified to species. Allergen extracts were prepared from sixteen of these isolated species and used for skin-prick testing of twenty-six patients. Fourteen of the total patients reacted to one or more of these extracts at 1:10 (w/v) concentrations. The most common positive skin responses (8/14 to 6/14) were found for Cladosporium cladosporioides, Alternaria tenuis, C. sphaerospermum, and Fusarium sp. The two Cladosporium species were also most commonly isolated in homes, but A. tenuis and Fusarium sp. were found only in 4% and less than 1% of the air samples, respectively. Epicoccum purpurascens and C. herbarum, which were isolated on approximately 10% of the plates, showed fewer skin reactions compared with the above. Positive skin-test response to the other ten study extracts ranged from 5/14 for two species of Aspergillus and Phoma glomerata, to 1/14 for Penicillium viridicatum; of these species, Aspergillus fumigatus was isolated in 3% of the home samples, the others were less than 1%. The findings suggest that fungal antigens from species found in homes are commonly associated with skin sensitization in an allergy clinic population with upper or lower respiratory allergy. No specific relationships were found, however, between the prevalence of fungal species in the home environment and their prevalence as skin-test allergens. PMID- 3349591 TI - Low specific IgE, IgG and lymphocyte reactivity in a group of patients developing anaphylaxis following a honey-bee sting. AB - Ten patients who developed severe generalized reactions following a honey-bee sting were investigated for the presence of specific IgE and IgG antibodies, and for lymphocyte reactivity following in-vitro honey-bee venom (HBV) stimulation. Five of the patients (high responders) showed high HBV-specific IgE and IgG levels, whereas the other five patients (low responders) showed low HBV-specific IgE and IgG levels. Mononuclear cells from the high responder group incorporated significant amounts of 3H-thymidine when activated with pure bee venom, whereas insignificant lymphocyte proliferation was observed in the low-responder group. It is concluded that, amongst HBV-sensitive patients, a group of low responders exists in whom the mechanism of anaphylaxis cannot be explained. PMID- 3349593 TI - Possible role for rotavirus in the development of cows' milk enteropathy in infants. AB - In order to test the hypothesis that rotavirus infection leads to IgE hypersensitivity to cows' milk, evidence of past rotavirus infection, as reflected by the presence of antibodies, was sought in two groups of children with cows' milk allergy. The groups were defined according to the time to react to milk challenge. In group I there were fifteen children with an adverse reaction within 40 min of milk challenge. The twenty-one children in group II had gastrointestinal reactions between 1 hr and 24 hr after milk challenge. The results showed a higher incidence of antibodies to rotavirus in group II than group I (P less than 0.05). Although group I patients had significantly higher levels of total and milk-specific IgE antibodies to cows' milk than those in group II, both patient groups had lower levels of serum IgG, IgA and IgM than a control population. No association between the presence of rotavirus antibodies and IgE hypersensitivity to cows' milk was found. However, an association between non-IgE milk enteropathy and previous rotavirus antibodies was demonstrated. PMID- 3349594 TI - Allergy to venom from bee or wasp: the relation between clinical and immunological reactions to insect stings. AB - Sixty-three patients, applying to the casualty ward after a bee or wasp sting, were tested. On the day of admission, and 4 weeks later, blood was sampled to measure specific IgE and IgG against bee and wasp venom and total IgE. Four weeks after the insect sting, all patients were examined with skin-prick test (1, 10 and 100 micrograms/ml), and intracutaneous test (0.05 ml of extract 1.0 microgram/ml). The amount of venom-specific IgE and IgG increased significantly during the 4-week period, venom-specific IgE was most pronounced in patients experiencing the most severe clinical reactions. However, no significant correlations were found between the results of the immunological tests carried out 4 weeks after the insect sting and the clinical reaction upon the insect sting. PMID- 3349595 TI - IgE and IgG antibody response to purified bee-venom antigens and peptides in four patients who had adverse reactions to immunotherapy. AB - The immunological response to individual bee-venom allergens was studied in blood samples collected at frequent intervals from four bee-venom allergic patients who had suffered systemic allergic reactions to injections of bee venom during immunotherapy. All had high IgE antibody levels, at the upper end of the range found in bee-sting allergic patients, and all had antibodies to the minor allergens at the time of the reactions. These did not, however, provide a simple explanation for the reactions that occurred. We were able to observe two interesting phenomena--in one patient IgE antibodies to the individual venom antigens appeared to be 'switched off' sequentially. In another, IgE antibodies to hyaluronidase rose substantially after 4 years of therapy. We believe that these results provide evidence to support the view that the regulation of IgE antibodies is controlled by mechanisms that are both isotype- and antigen specific. PMID- 3349596 TI - IgG antibodies against polyisocyanates in car painters. AB - A group of thirty car painters exposed to vapours and aerosols of paint containing prepolymer andmonomer of hexametylene diisocyanate (HDI) was investigated. Specific antibodies against monomer HDI and prepolymerized HDI were analysed with RAST (IgE) and ELISA (IgG) assays after conjugation of the haptens with human serum albumin. There was no significant increase of serum IgG antibodies against HDI monomer, nor of specific IgE antibodies against HDI monomer or prepolymer. Specific IgG antibodies against prepolymerized HDI were significantly increased, as compared with non-exposed referents (medians 0.11 vs 0.03 absorbance (A]. Six car painters were found to have specific IgG antibodies of subclass 4 against HDI prepolymer, four also against HDI monomer. This shows an association between exposure and specific IgG antibodies. Thirteen subjects had suffered symptoms of rhinitis and/or conjunctivitis, and ten had symptoms from the bronchi (two asthma). There was no significant association between symptoms and levels of specific antibodies. Most of the symptoms were slight and unspecific, probably due to irritative effects of the exposure. PMID- 3349597 TI - Stability and electrophoretic characteristics of creatine kinase BB extracted from human brain and intestine. AB - Creatine kinase (CK; EC 2.7.3.2) isoenzyme BB extracted from brains of rats reportedly undergoes modification at 37 degrees C, leaving an electrophoretic variant that accounts for most of the residual CK activity. This variant, called CK-BB', migrates on electrophoresis similarly to creatine kinase isoenzyme MB. Using electrophoresis and immunoinhibition with antiserum to creatine kinase isoenzyme MM, we found CK-BB to be the only identifiable cytoplasmic isoenzyme in surgical samples from human brain and intestine. In contrast, we found that some samples of brain obtained at autopsy contain CK-BB'. We also found that CK-BB extracted from human brain was converted to CK-BB' upon incubation in serum or plasma at 37 degrees C. We found a similar development of CK-BB' in incubation mixtures of serum or plasma containing CK-BB obtained from surgical samples of human intestine. The development of CK-BB' during infarction of the gastrointestinal system may thus be a source of false-positive CK-MB in the laboratory verification of myocardial infarction when electrophoresis is used as the only method to identify CK isoenzymes. PMID- 3349598 TI - Liquid-chromatographic assay of ibuprofen enantiomers in plasma. AB - This stereospecific "high-performance" liquid-chromatographic (HPLC) assay is suitable for pharmacokinetic studies of ibuprofen (IB). Very efficient extraction of the drug and internal standard, (+/-)-2-(4-benzoylphenyl)butyric acid, from plasma with isooctane/isopropanol (95/5, by vol) is followed by sequential reaction of the enantiomers with ethyl chloroformate and (S)-(-)-1-(1 naphthyl)ethylamine. The reactions take place at ambient temperature in less than 4 min. The naphthylethylamide derivatives of IB enantiomers and internal standard are then extracted into chloroform. After the organic layer is evaporated, the reconstituted residue is chromatographed at ambient temperature on a C18 reversed phase column with a mobile phase of acetonitrile/water/acetic acid/triethylamine (55/45/0.1/0.02 by vol) at a flow rate of 1 mL/min. The IB diastereoisomers, detected at 232 nm, are free of interfering peaks and have a resolution factor of 2.2. Within the examined enantiomer concentration range of 0.1 to 20 mg/L in plasma, the peak-area ratios varied linearly with the corresponding IB concentrations. We used the assay to study the pharmacokinetics of IB enantiomers in plasma of a subject who took a single 600-mg dose of racemic drug. PMID- 3349600 TI - New approach to competitive lanthanide immunoassay: time-resolved fluoroimmunoassay of progesterone with labeled analyte. AB - This solid-phase competitive europium immunoassay of progesterone in plasma relies on antigen labeling. With this new approach, time-resolved fluoroimmunoassay can attain sensitivity and precision similar to that of conventional radioimmunoassay. The europium-labeling involves coupling diethylenetriaminepentaacetic acid (chelating agent for Eu3+) to a progesterone protein conjugate. The solid-phase antibody is immobilized inside polystyrene tubes in which plasma samples (50 microL) are assayed directly, without preliminary extraction. After incubation in the presence of trichloroacetic acid, the tubes are washed and the fluorescence intensity of europium is measured by time-wavelength-resolved fluorometry, with a nitrogen laser as the pulsed excitation source. Progesterone values obtained by this procedure agreed well with those obtained by radioimmunoassay (r = 0.98, n = 97). The detection limit was equivalent to that of most RIAs (0.2 micrograms/L). PMID- 3349599 TI - A simple method for clinical assay of superoxide dismutase. AB - This assay for superoxide dismutase (SOD, EC 1.15.1.1) activity involves inhibition of nitroblue tetrazolium reduction, with xanthine-xanthine oxidase used as a superoxide generator. By using a reaction terminator, we can determine 40 samples within 55 min. One unit of activity of pure bovine liver Cu,ZnSOD and chicken liver MnSOD was expressed by 30 ng and 500 ng of protein, respectively. The mean concentrations of Cu,ZnSOD as measured by this method in blood from normal adults were 242 (SEM 4) mg/L in erythrocytes, 548 (SEM 20) micrograms/L in serum, and 173 (SEM 11) micrograms/L in plasma. The Cu,ZnSOD concentrations in serum and plasma of patients with cancer of the large intestine tended to be less and greater than these values, respectively, but not statistically significantly so. PMID- 3349601 TI - Assessment of proton nuclear magnetic resonance spectroscopy for detection of malignancy. AB - Water-suppressed proton nuclear magnetic resonance spectra were generated (by using 360 and 500 MHz systems) from human plasma and serum samples taken from 35 apparently healthy individuals, 52 patients with overt malignancies, and 37 patients with hypertriglyceridemia (triglycerides greater than 200 mg/dL or 2.26 mmol/L). The line widths from the lipoprotein-lipid methylene and methyl resonances at approximately 1.3 and 0.9 ppm were averaged by the method of Fossel et al. (N Engl J Med 1986;315:1369-76), but, contrary to their findings, we were unable to distinguish normal individuals from those with malignant tumors (e.g., mean +/- SD line width at 360 MHz: normal group = 32.9 +/- 3.6 Hz, malignant group = 28.3 +/- 4.9 Hz). The average line-width measurements (y), however, varied with the triglyceride content (x, mg/dL) of the plasma or serum as follows (logarithmic transformation of the data determined at 360 MHz and regression analysis): y = 110 (x-0.27). Data from both nonmalignant and malignant specimens fit this equation, the coefficient of correlation being -0.91. These findings suggest that considerable caution should be used in interpreting water-suppressed proton NMR spectra for cancer detection. PMID- 3349602 TI - Quinidine-induced inhibition of leukocyte esterases. AB - We have demonstrated the feasibility of a system based on image processing to measure enzyme activity inside morphologically classified individual cells. When used in this system, quinidine inhibited naphthol AS-D chloroacetate esterase in polymorphonuclear neutrophils and alpha-naphthyl acetate esterase and alpha naphthyl butyrate esterase in monocytes. These effects were dependent on the duration of exposure and on drug concentration. Dose-effect relationships were established and the concentration at which 50% inhibition (ID-50) occurred was used as a reference point to compare the toxicity of different compounds. Chloroquine, primaquine, and quinine (which, like quinidine, possess a quinoline ring) also affected the esterases, but had no effect on several other enzymes. Neostigmine inhibited the esterases we studied but only at a very high concentration. Various chemicals inhibited the enzymes within the cells, as has been demonstrated for the enzymes in plasma. PMID- 3349603 TI - Simultaneous determination of catecholamines and serotonin by liquid chromatography, after treatment with boric acid gel. AB - We describe a liquid-chromatographic method for simultaneously determining norepinephrine, epinephrine, dopamine, and serotonin in 0.5 mL of human plasma. These analytes are purified on boric acid gel from Aldrich, separated on a reversed-phase C18 column, and detected electrochemically at +600 mV. Absolute recoveries of internal standards were 84% for 3,4-dihydroxybenzylamine and 57% for N-methylserotonin. Reproducibility was good to excellent, depending on the concentration of the analytes. A chromatographic run is complete in 40 min, but this can be shortened by about half when the determination of only serotonin is required, by increasing the column temperature from 40 degrees C to 60 degrees C. PMID- 3349604 TI - Measurement of cholesterol in serum by gas chromatography/mass spectrometry at moderate mass resolution, with a nonendogenous cholesterol isomer as internal standard. AB - We describe a gas chromatography/mass spectrometry method for the quantitative analysis of cholesterol in serum. A structural isomer of cholesterol, 7,(5 alpha) cholesten-3 beta-ol, is used as an internal standard, its primary advantage being its lesser cost relative to that of a stable-isotope-labeled analog. Analysis of the National Bureau of Standards Certified Reference Serum (SRM 909) was used to validate the method. The results show this method to be highly accurate (bias = 0.6%) and precise (CV = 1.6% between-run, 1.2% within-run). The performance of this method is, therefore, sufficiently good to allow its use as a reference method for determinations of cholesterol in serum. PMID- 3349605 TI - Effect of creatine kinase-MM subtype composition on a CK-MB immunoinhibition assay. AB - Immunoinhibition (INH) by use of polyclonal anti-human CK-M antibody may be used to measure CK-MB in serum. Previous studies have shown that inhibiting antibodies prepared against purified muscle extracts may inhibit CK-MM by greater than 99%. Using patients' sera and muscle homogenates incubated with human serum, we studied the effect of CK-MM subtype composition on an INH assay. We found that with increasing time from the CK-releasing event, e.g., myocardial infarction, or with longer in vitro incubation, the proportion of CK-MM1 increased and the proportion of uninhibited CK-MM increased from 0.2% to 0.7-0.8%. As a consequence, CK-MB activity may be overestimated by as much as 1.6% of total CK when uncorrected INH results are used. Inhibition was maximal in samples containing 100% CK-MM3, the tissue subtype. Because of the time-dependent change in CK-MM subtypes, published results for INH from studies in which CK-MM purified from muscle was used may not be directly applicable to clinical specimens. PMID- 3349606 TI - Cis-4-decenoic acid in plasma: a characteristic metabolite in medium-chain acyl CoA dehydrogenase deficiency. AB - The profile of organic acids in plasma of patients with a deficiency of medium chain acyl-CoA dehydrogenase (EC 1.3.99.3) was determined by gas-liquid chromatography of trimethylsilylated derivatives of the acids isolated by ethyl acetate extraction. All 13 patients had increased concentrations of free octanoate, cis-4-decenoate, and decanoate in their plasma. Cis-4-decenoate, an intermediary metabolite of linoleic acid, is pathognomonic of medium-chain acyl CoA dehydrogenase deficiency. This metabolite does not accumulate in plasma after oral loading with medium-chain triglycerides, in contrast to octanoate and decanoate. Two postmortem plasma samples from victims of infant sudden-death syndrome had detectable octanoate and decanoate, but cis-4-decenoate could not be detected. The identification of cis-4-decenoate in plasma may be an aid in the diagnosis of an inherited defect in oxidation of medium-chain fatty acids. PMID- 3349607 TI - Excretion of digoxin-like immunoreactivity in urine of normal subjects: correlations with excretion of creatinine and electrolytes. AB - To verify whether there is a variation in the 24-h urinary excretion of digoxin like immunoreactivity (DLIS) in humans, we studied 18 normal adults, who collected their urines for 24-h in several portions. We then measured DLIS (by means of a sensitive RIA method), creatinine, sodium, and potassium concentrations in the urine samples. The mean urinary excretion rate for DLIS in the complete 24-h collection was 84.8 (SD 31.3) pg/min. The mean DLIS urinary excretion rate calculated for overnight collections was significantly lower than those of afternoon collections (P less than 0.01) and the 24-h collection (P less than 0.05). Significant positive correlations were found between urinary DLIS and excretion rates for creatinine (r = 0.347, P = 0.0016), Na+ (r = 0.232, P = 0.038), and K+ (r = 0.323, P = 0.003), respectively. Our data suggest that urinary excretion of DLIS is higher during "active" hours of the day, especially in the afternoon, than at rest, during the night. PMID- 3349608 TI - Changes in the concentration of testosterone in serum during the menstrual cycle, as determined by liquid chromatography. AB - We used a newly developed high-performance liquid chromatographic (HPLC) method to determine the concentration of testosterone in serum from women and compared the results with those obtained by conventional radioimmunoassay. We used a conventional silica gel column and organic solvent mixture (ethanol plus n-hexane containing a small amount of water). The detection limit for testosterone was as low as 0.2 micrograms/L, sufficient to correctly determine the concentration of the hormone in serum from women. For the calibration curve, we plotted the peak height ratio of testosterone to 19-nortestosterone. The menstrual-cycle-related rhythm of the concentration of testosterone in serum was related to follicular and luteal phase-shifting, the concentration being considerably greater in the luteal phase than in the follicular phase. In contrast, RIA showed only minor and irregular fluctuation in the concentrations of the hormone throughout the menstrual cycle. When we used the HPLC to measure the hormonal change in a woman with an irregular menstrual cycle, we found that her testosterone concentration increased abnormally early after menstruation. PMID- 3349609 TI - Interference by endogenous glycerol in an enzymatic assay of phosphatidylglycerol in amniotic fluid. AB - We investigated the possibility of interference by endogenous glycerol with the enzymatic measurement of phosphatidylglycerol in amniotic fluid. Phosphatidylglycerol is an important indicator of fetal lung maturity. The concentrations of glycerol and phosphatidylglycerol in amniotic fluid were measured by using a coupled enzymatic assay with and without phospholipase D (EC 3.1.4.4). The precision of the assay was acceptable (within-run CV = 1.2%, between-run CV = 4.8%). Endogenous glycerol content was demonstrated to be approximately 10-20 times that of phosphatidylglycerol. This high proportion of endogenous glycerol in amniotic fluid would preclude the accurate enzymatic determination of amniotic fluid phosphatidylglycerol unless the glycerol is first removed. Nor can the actual phosphatidylglycerol concentration be determined by subtracting the endogenous glycerol concentration from the total glycerol, which includes that glycerol derived from phosphatidylglycerol. With a usual range of 9 +/- 7 mumol/L, the error for a given phosphatidylglycerol measurement of +/- 6.6 mumol/L (+/- 2 SD) clearly is too high for this assay to be clinically useful. There was no correlation between concentration of endogenous glycerol or apparent phosphatidylglycerol in amniotic fluid and the lecithin/sphingomyelin ratio of the sample. PMID- 3349611 TI - Melanogenuria: laboratory evaluation of the qualitative Thormahlen and ferric chloride tests and their clinical utility. AB - Malignant melanoma, a disease that is increasing in occurrence and medical concern, is characterized by the excretion of melanogens. Two qualitative tests are recommended for melanogen detection, the Thormahlen test and the ferric chloride test. We evaluated the laboratory and clinical performance of these tests by subsequently re-evaluating 201 urine samples that had been submitted for routine melanogen analysis. We used (a) Thormahlen, (b) ferric chloride, (c) small-scale thin-layer chromatography, and (d) spectrophotometry. Nearly 30% of Thormahlen test results were equivocal. The ferric chloride test was of no value in itself or in categorizing equivocal Thormahlen results as positive or negative. The small-scale chromatography was irreproducible. Prompt scanning of the Thormahlen reaction product was helpful in classifying equivocal results. History review of 121 histopathologically diagnosed melanoma patients indicated that these qualitative assays were of no clinical value in the diagnosis or monitoring of melanoma patients. PMID- 3349613 TI - Frozen storage of serum does not affect cholesterol and triglyceride concentration in lipoproteins as separated by gradient ultracentrifugation. PMID- 3349612 TI - Fibronectin concentrations in plasma of healthy pre-term, full-term, and sick full-term neonates. PMID- 3349610 TI - Semi-automated direct colorimetric measurement of creatine kinase isoenzyme MB activity after extraction from serum by use of a CK-MB-specific monoclonal antibody. AB - This semi-automated colorimetric assay for the MB isoenzyme of creatine kinase (EC 2.7.3.2) is based on a monoclonal antibody ("Conan-MB") specific for this isoenzyme and is a modification of a previously published method (Vaidya et al., Clin Chem 1986;32:657-63). A 0.64-cm bead coated with 2 to 3 micrograms of antibody is incubated with 100 microL of serum and 10 microL of 0.2 mol/L beta mercaptoethanol for 1 h at room temperature, to extract CK-MB. The beads are washed with de-ionized water and incubated with CK substrate for 45 min at 37 degrees C. A solution containing trans-1,2-diaminocyclohexane-N,N,N', N' tetraacetic acid, p-iodonitrotetrazolium violet, and diaphorase is added and the resulting colored product is measured at 492 nm. The standard curve is linear to 200 U of CK-MB per liter, and analytical recovery is 97-113%. Total assay CV for low (9.7 U/L) and high (50.7 U/L) quality-control materials was 14.1% (n = 1878) and 11.6% (n = 1842), respectively. CK-MB activity correlated well (r = 0.978, n = 226) with CK-MB measured by a two-site mass immunoassay, and 99.4% of samples with CK-MB greater than or equal to 12 U/L (n = 347) were verified by electrophoresis on agarose. PMID- 3349614 TI - Effect of high creatine content on the Kodak single-slide method for creatinine. PMID- 3349615 TI - Clinical evaluation of a fluorescence polarization immunoassay for quantifying C reactive protein. PMID- 3349616 TI - Cyclosporine concentrations in plasma at 37 degrees C are not predictable from concentrations measured in whole blood at room temperature. PMID- 3349617 TI - Free thyroxin in familial dysalbuminemic hyperthyroxinemia, as measured by five assays. PMID- 3349619 TI - Monitoring quinidine concentrations in serum: discrepancies in results by fluorometry and immunoassay. PMID- 3349618 TI - Instability of calibration curves of liquid-chromatographic techniques with electrochemical detection: role of the detector. PMID- 3349620 TI - Stability of total calcium as determined by using Kodak Ektachem dry-film methodology. PMID- 3349621 TI - False-positive Hb S in the Helena Sickle-Thal Quik Column method, owing to the presence of another hemoglobin variant. PMID- 3349622 TI - An inherited albumin variant with enhanced affinity for the Amerlex thyroxin analog. AB - We describe two siblings with artefactually increased results for free thyroxin in serum as measured with the Amerlex analog method, despite normal thyroxin transport. The cause of the artefact is identified as a variant albumin with enhanced affinity for the Amerlex thyroxin-analog. PMID- 3349623 TI - Drug testing in the military--technical and legal problems. AB - The Armed Forces drug-testing program has been in operation since 1971. Since that time, its goals, capabilities, and methods of operation have undergone extensive evolution and change. As these laboratories developed, they helped to establish many of the currently accepted operating standards for drug screening. For laboratories considering entry into the business of drug screening, an examination of the evolution and current operation of the military laboratories will be of benefit. It will help to define the currently accepted standards and NIDA guidelines and assist them to avoid the types of problems that were encountered by the military laboratories. PMID- 3349624 TI - Choriogonadotropin in urine or serum for detection of ectopic pregnancy? PMID- 3349625 TI - What determines the degree of hyponatremia in hyperglycemia? PMID- 3349626 TI - Jaffe reaction interference. PMID- 3349628 TI - Clinical significance of subnormal values for thyrotropin. PMID- 3349627 TI - Organization of a field laboratory at an ultra marathon. PMID- 3349629 TI - More on quantification of urinary protein with benzethonium chloride. PMID- 3349630 TI - Heating drug-assay samples to minimize AIDS risk. PMID- 3349631 TI - Phosphohexose isomerase in lung cancer. PMID- 3349633 TI - Analysis of the fatty acid composition of erythrocyte phospholipids by a base catalysed transesterification method--prevention of formation of dimethylacetals. AB - A sensitive method for the analysis of the fatty acid composition of erythrocyte phospholipids with capillary column GLC is described. Under the assay conditions (base catalysed transesterification with sodium methoxide), only the fatty acids of the phospholipids are converted to their methylesters. The alkenyl ether chains of the plasmalogens are not transmethylated. This eliminates the need for thin layer chromatography for the separation of dimethylacetals and esterified fatty acids. The method is suitable for the measurement of the fatty acid patterns of erythrocyte phospholipids in small blood samples. PMID- 3349632 TI - Changes in the bone and liver isoenzymes of alkaline phosphatase in postmenopausal women being treated with norethisterone. AB - The effects of norethisterone therapy on alkaline phosphatase isoenzyme activities were studied in a group of postmenopausal women. There was a significant fall in total alkaline phosphatase activity after 8 wk which was still in evidence after 24 wk. Both bone and liver alkaline phosphatase isoenzyme activities were decreased during the first 16 wk on treatment, but after 24 wk only the bone phosphatase activity was significantly lower than the pretreatment level. The other biochemical indices of bone metabolism and liver function were also measured during the study. The results indicate that bone specific alkaline phosphatase activity is a more sensitive index of bone activity than total alkaline phosphatase and that monitoring of total activity may in some instances be misleading. PMID- 3349634 TI - Differences in the thermal stability of liver alkaline phosphatase between different ethnic populations. PMID- 3349635 TI - A sensitive, direct colorimetric assay of serum iron using the chromogen, nitro PAPS. AB - A direct colorimetric method is presented for the determination of serum iron in 0.1-ml sized samples, using a new, water-soluble, reagent, 2-(5-Nitro-2 pyridylazo)-5-(N-propyl-N-sulfopropylamino)phenol Na salt (epsilon 585 nm = 9.4 X 10(4) l/mol per cm). Interference of copper and zinc in sera can be eliminated entirely by forming copper- and zinc-thioglycollate complexes immediately upon the dissociation of the protein-bound iron, copper and zinc by thioglycollate and sodium dodecyl sulfate. The serum blank was minimized by the use of sodium dodecyl sulfate as a protein denaturant. Within-run and between-run precision (CV) were in the range of 0.7-2.9% and 1.1-3.6%, respectively, depending on the serum iron content. A good correlation (r = 0.995) was obtained between this method and the reference method proposed by the International Committee for Standardization in Hematology. PMID- 3349636 TI - Quantitation and characterization of urinary glycosaminoglycans in healthy subjects and patients with mastocytosis. AB - The urinary glycosaminoglycans (uGAG) in eight patients (four adults and four children) with mastocytosis and eleven healthy subjects (five adults and six children) were examined for evidence of heparin and chondroitin sulfate E. The excretion of uGAG to urinary creatinine (uCr) in these patients was found to be 10.36 micrograms/mg for the children and 0.98 micrograms/mg for the adults, neither significantly different from healthy controls (p greater than 0.2). The uGAG was found to have a molecular mass between 10 kDa and 60 kDa by high performance liquid chromatography (HPLC). The content of the uGAG was found to consist of chondroitin sulfates without any evidence of heparin as assessed by specific chondroitinase ABC susceptibility. Disaccharide analysis following chondroitinase ABC digestion by HPLC Partisil-10 Pac separation revealed no evidence of chondroitin sulfate E and no differences in relative distribution of 0-, 4-, and 6-sulfated disaccharides between patients and healthy controls. PMID- 3349637 TI - Situational anxiety and blood pressure lability in the physician's office. AB - In order to evaluate the association between situational anxiety levels and blood pressure variability during physician's office visits, 19 patients were assessed at the beginning of the visit and before and after being examined by the physician. Assessment included blood pressure measurement as well as self-report of current anxiety level. Previous findings that systolic readings do significantly diminish over the course of the visit were replicated for both hypertensive and normotensive patients, accompanied by correlative decreases in state anxiety. Diastolic blood pressure readings were more stable and less associated with fluctuations in state anxiety, except in patients with initially higher diastolic readings. Results were interpreted as indicating the importance of using more than one blood pressure measurement in diagnosing hypertension and monitoring its management. In particular, patients' anxiety responses upon entering the examining room may produce artificial elevations. PMID- 3349638 TI - Papillary muscle structure-function relations in the aging spontaneously hypertensive rat. AB - Isolated left ventricle papillary muscle mechanics and structure were studied in male spontaneously hypertensive (SHR) rats and two control groups of animals, the normotensive Wistar (NR) and the Wistar-Kyoto rat (WKY). Active tension and its first derivative (dT/dtmax) normalized for muscle cross-sectional area were increased in preparations from the SHR at all ages studied relative to control groups (P less than 0.01). However, when these parameters were normalized for myofibrillar cross-sectional area determined from electronmicroscopic point counting data, differences between groups were no longer significant. Force velocity relations provided no evidence for a depression of shortening velocity at any load in the SHR at any age relative to the two control groups. The duration of mechanical activity, as determined by time-to-peak isometric tension and analysis of muscle force-velocity-time relations, was prolonged only in the 18 month old SHR (P less than 0.01). Thus, while changes in isolated muscle performance occur at a time when hemodynamic impairment is reported in the intact animal (male 18 month SHR), no evidence for depression of isolated muscle function is seen in the SHR at 6, 12 or 18 months of age. PMID- 3349639 TI - Decreased hindquarters venous distensibility during high salt intake in stroke prone spontaneously hypertensive rats. AB - This study was done to examine whether high salt intake decreases venous distensibility in stroke-prone spontaneously hypertensive rats (SHR-sp). Ten weeks old male SHR-sp and normotensive Wistar-Kyoto rats (WKY) were fed either high (8%) or pressure-volume curves were obtained by infusing Krebs-Henseleit solution retrograde into the inferior vena cava at a rate of 12 or 2.1 ml/min. After 3 weeks of dietary treatment, high salt intake shifted the venous pressure volume curves at maximal venodilatation caused by nitroprusside toward the pressure axis in SHR-sp but not in WKY. The venous pressure-volume curve during interruption of infusion was also shifted toward the pressure axis in SHR-sp on high salt diet as compared with that in SHR-sp on normal salt diet. Water content and thickness of the smooth muscle layer of the venous wall were not different between the two groups of SHR-sp. These results suggest that high salt intake for 3 weeks decreased hindquarters venous distensibility at maximal venodilatation in SHR-sp but not in WKY. The salt-induced decrease in venous distensibility in SHR sp might be related to changes in interstitial space compliance or the adventitia since water content or thickness of the smooth muscle layer of the venous wall was not altered. PMID- 3349640 TI - Predisposition to hypertension in rat pups from renal hypertensive dams. AB - We determined that a predisposition to hypertension could be transmitted by a nongenetic, renal hypertensive (HT) mother to her pups. The pups of one-kidney: one clip Goldblatt (1K:1C) hypertensive female rats and of sham operated normotensive female rats were subjected to the 1K:1C procedure at 28 days of age and tail cuff blood pressures (BP) were determined. After surgical induction of hypertension, HT male pups of HT dams had a significantly greater (p less than .05) BP by 14 days after surgery (194 +/- 8 mm Hg) than did HT male pups of normotensive (NT) dams (169 +/- 6 mm Hg). A similar trend (p less than .08) was observed for the HT female pups of HT dams (185 +/- 7 mm Hg) compared to HT females from NT dams (163 +/- 4 mm Hg). Thus, in utero exposure of pups to a chronic HT state alters the response of the pups to the surgical induction of hypertension. Furthermore, the results suggest that transfer of a predisposition to hypertension from mother to offspring occurred during the pregnancy/lactation period. PMID- 3349641 TI - Pancreas divisum: controversial clinical significance. PMID- 3349642 TI - Halothane hepatitis. AB - Hepatitis following halothane anaesthesia may take two forms: a mild self limiting disease or a more severe hepatitis with a high mortality. Whether these two forms represent two distinct entities or ends of a spectrum is unclear. Severe hepatitis is commoner after multiple exposures and has many of the characteristics of an immune-mediated hypersensitivity reaction. The incidence is very low; the best, albeit unsatisfactory, estimate of the incidence is about 1 in 3,700 patients with multiple halothane exposures. The mechanism of liver damage is uncertain: in some circumstances halothane may be directly hepatotoxic, but it remains to be conclusively proved that immune mechanisms are responsible. Studies from our unit have suggested that halothane hepatitis can positively be diagnosed by demonstration of antibodies reacting with halothane-altered liver cell determinants. The incidence of the condition can be reduced by taking a full anaesthetic history and avoiding the use of halothane in the high-risk patients, namely those who have had recent previous halothane anaesthesia and those who have had jaundice or unexplained post-operative pyrexia following earlier halothane anaesthetics. When halothane hepatitis has occurred, treatment is purely supportive with the possibility of transplantation for those in grade IV encephalopathy. PMID- 3349643 TI - Suppression of contact hypersensitivity by short-term ultraviolet irradiation: I. Immunosuppression by serum from irradiated mice. AB - Serum from UV-irradiated mice was shown to be immunosuppressive in vitro and in vivo. It suppressed leucocyte adherence inhibition reactions of cells from sensitized syngeneic and allogeneic mice, and suppressed the development of contact hypersensitivity after passive transfer to mice. Supernatants of cultures of spleen cells from irradiated mice were also suppressive. The suppressive factors in sera and culture supernatants were non-dialysable. The suppressive effect of UV irradiation was abrogated by cyclophosphamide, but this restored reactivity was still inhibited by serum from irradiated donors; this suggests that the serum factor requires T suppressor cells for its production but not for its action. The level of interleukin 1 (IL-1) was not raised in serum from UV irradiated mice; thus the serum factor appears not to be IL-1. PMID- 3349644 TI - Augmentation of delayed-type hypersensitivity to high dose sheep erythrocytes by cyclosporin A in the mouse: influence of drug dosage and route of administration and analysis of spleen cell populations. AB - When administered by various routes 48 h before a high systemic dose (10 degrees) of sheep red blood cells (SRBC), Cyclosporin A (CsA) prevented the suppression of delayed-type hypersensitivity (DTH) reactions elicited 4 days later. Augmentation of DTH was observed over a wide range (5-200 mg/kg) and with circulating CsA levels ranging below 45 ng/ml at the time of immunization or antigen challenge. Splenic lymphocytes from vehicle- and CsA-treated mice exhibited good proliferative responses to mitogen in vitro, but only those from CsA-treated animals responded to antigen. Expression of DTH was associated with a progressive, 2-fold increase in the absolute numbers of splenic L3T4+ cells, whereas no significant alteration in the number of Lyt-2+ lymphocytes was recorded. B cell and macrophage numbers in the spleen were unaffected by CsA. In contrast to its potentiating effects on cell-mediated immunity, CsA caused profound (up to 100%) suppression of the concomitant production of splenic anti SRBC IgM-secreting plasma cells. Circulating anti-SRBC antibody levels were also markedly reduced. These data show that CsA can permit induction of TDTH, whilst suppressing T-dependent humoral immunity and without significant change in absolute numbers of Lyt-2+ cells. PMID- 3349645 TI - Direct immunomagnetic quantification of lymphocyte subsets in blood. AB - A method is described where superparamagnetic polymer microspheres coated with monoclonal antibodies (MoAb) are used for the direct and fast quantification of the absolute number of cells of various lymphocyte subsets in blood. Blood samples were incubated with microspheres coated with a subset specific MoAb. Using a magnet the microsphere-rosetted cells were isolated and washed. Following lysis of the cell walls to detach the microspheres, the cell nuclei were stained with acridine orange and counted in a haemocytometer using an immunofluorescence microscope. With MoAb specific for CD2, CD4, CD8 and CD19, reproducible absolute counts of the corresponding lymphocyte subsets were obtained which correlated closely with those obtained by an indirect quantification method. PMID- 3349646 TI - Immunity to hepatitis B: analysis of antibody and cellular responses in recipients of a plasma-derived vaccine using synthetic peptides mimicking S and pre-S regions. AB - The potential of a panel of synthetic HBsAg peptides as components of a synthetic hepatitis B vaccine was assessed. Each was used in turn as probes to analyse human immune responses to a licensed plasma-derived HBV vaccine. Both humoral and cellular responses were analysed with synthetic peptides representing residues 124-147 of the surface antigen of the virus (HBsAg) and residues 126-140 of the pre-S2 region. Antibody levels and affinities were assessed in radioimmunoassays with synthetic linear and cyclical forms of surface antigen peptides 124-137 and 139-147, with the gp30p25 polypeptide complex of HBsAg and with the linear pre-S2 peptide 126-140. Levels and affinities of antibodies to the antigens increased with time during immunization. However, antibodies binding the cyclical peptide representing amino acids 139 to 147 (C139) were present at higher levels and had higher affinities than were antibodies binding the other peptides, indicating that C139 more closely approximates a domain on the native antigen than do the other peptides. No humoral responses were measured with the pre-S2 peptide. Cellular responses were assessed by in vitro stimulation of peripheral blood lymphocytes by HBsAg and by the synthetic peptides. All vaccine recipients had demonstrable lymphocyte responsiveness to HBsAg after both second and third doses of the vaccine. Of the S and pre-S peptides used, only L124 failed to induce lymphocyte stimulation in all recipients. However, there were individual variations in both the time of initial responsiveness to peptides and in the level and time of maximal stimulation. Stimulation by native HBsAg particles, which corresponded to the appearance of anti-HBs antibody, preceded that observed using synthetic peptides. In all recipients, maximum stimulation indices with HBsAg were significantly higher than those observed with the peptides. In contrast to the absence of pre-S2 antibody, the lymphocytes from all recipients showed positive stimulation in response to the peptide representing residues 126 140 of the pre-S2 region. None of these individuals had antibodies to pre-S or an HB core peptide sequence nor did their lymphocytes respond to a synthetic peptide representing an HB core sequence. PMID- 3349647 TI - Mechanism of action of glucocorticoid-induced immunoglobulin production: II. Requirement for fetal calf serum. AB - Corticosteroids have been reported to stimulate immunoglobulin (Ig) production by otherwise unstimulated peripheral blood mononuclear cells. In this paper we confirm that observation but report the necessity for an additional minor antigenic stimulus. Lymphocytes cultured with HB101, a complete medium not requiring serum supplement, did not increase Ig production after addition of hydrocortisone, but did if small concentrations (1-10%) of fetal calf serum were added. Various antigens such as candida, tetanus, and albumin of different sources could substitute for fetal calf sera in allowing corticosteroids to stimulate Ig production in resting lymphocytes. We conclude that corticosteroids do not stimulate Ig production by lymphocytes de novo; rather, corticosteroids greatly enhance the Ig production stimulated by the foreign antigens present in fetal calf sera. PMID- 3349648 TI - Enzyme-linked immunosorbent assay for detection of retroviral gp70 and gp70-anti gp70 immune complexes in sera from SLE mice. AB - Since a retroviral envelope glycoprotein, gp70, present in sera is prominently involved in the pathogenesis of murine systemic lupus erythematosus (SLE), the detection of gp70-anti-gp70 immune complexes (gp70 IC) is particularly useful for the study of murine SLE. To facilitate the detection of gp70 and gp70 IC, we have developed a simple and sensitive enzyme-linked immunosorbent assay (ELISA). Using an affinity column coupled with whole mouse serum proteins containing serum gp70 or with Rauscher murine leukaemia virus (MuLV), antibodies specific to serum gp70 or to Rauscher MuLV gp70 were purified from hyperimmune goat anti-Rauscher MuLV gp70 antisera. Only affinity-purified anti-serum gp70 fraction, but not anti Rauscher MuLV gp70 fraction, was able to detect serum gp70 efficiently in the ELISA, because only a minor fraction of goat anti-Rauscher MuLV gp70 antibodies is cross-reacting with serum gp70. This procedure could be applied to other antigen-antibody systems, in which only antibodies to heterologous cross-reacting antigens are available, to detect free and antibody-complexed antigens in pathological sera. PMID- 3349650 TI - Evidence for anti-tubulin autoantibodies in the form of immune complexes in human sera. AB - Anti-tubulin antibodies were studied in normal human serum either maintained at neutral pH to measure the free antibody activity (FAA) or treated at pH 2.8 to measure the total antibody activity (TAA): FAA + the antibody activity in the form of immune complexes (ICAA). Anti-tubulin antibody activities were assessed by measurements of the capacity of serum immunoglobulins to bind pure 125I labelled tubulin in a liquid phase radioimmune assay or to immunoprecipitate unlabelled tubulin revealed by Western blot using anti-alpha- or anti-beta tubulin monoclonal antibodies. Acid buffer-treated serum and untreated serum at a 1:200 dilution immunoprecipitated about 35% and 4% of labelled tubulin, respectively. TAA was therefore 8- to 10-fold higher than FFA. Anti-tubulin antibody titres corresponding to TAA and FAA were about 1:20,000 and 1:500, respectively. The Western blot analysis confirmed that the acid buffer-treatment of the serum dramatically increased the capacity of serum immunoglobulins to immunoprecipitate tubulin. TAA was studied in patients with Graves' disease with elevated FAA. TAA of the sera of control subjects and patients with Graves' disease were not significantly different, so an increase of FAA was related to a decrease of ICAA. These results indicate that (a) normal human serum contains high levels of anti-tubulin antibodies in the form of immune complexes which are dissociated by an acid buffer treatment, (b) these immune complexes exist in the presence of a small excess of free anti-tubulin antibodies, (c) the equilibrium between free and immune complex-bound anti-tubulin antibodies could be altered in patients with autoimmune diseases. PMID- 3349649 TI - An idiotope-specific autoantibody in SLE. AB - The public idiotype Id-16/6 and the public idiotope Id-LLa were originally defined on the same human monoclonal anti-DNA antibody, but they are also known to occur separately on other anti-DNA antibodies. We sought the presence of these immunoglobulin variable region markers in purified immunoglobulins from the serum of nine patients with systemic lupus erythematosus (SLE) and 33 healthy donors. Sera from five patients were positive for Id-16/6, and five were positive for Id LLa. The immunoglobulin preparations were passed over a Sepharose-Id-16/6 column in order to recover auto-anti-idiotypes. An eluate of that column was obtained from the immunoglobulin preparation of one patient whose serum was Id-16/6+ and Id-LLa-. This eluate was shown by competition assay to bind to IdLLa. This is the first demonstration of spontaneously arising human auto-anti-idiotypes against a specific idiotypic system in SLE. The results suggest that antibodies against the Id-LLa idiotope may play a role in immunoregulation. PMID- 3349652 TI - The effect of thymectomy on the development of nephropathy in spontaneous thymoma rats of the BUF/Mna strain. AB - A close relationship was assumed between the developments of nephropathy and thymoma in the previous study, in which the effect of introduction of the rat nude gene was studied in high thymoma BUF/Mna rats. In this paper, the effect of neonatal thymectomy on the development of nephropathy was examined to clarify the relationship between these two lesions in BUF/Mna rats. The average amount of urinary protein excreted from sham-operated and thymectomized BUF/Mna rats was 30.8 +/- 17.1 and 40.0 +/- 20.0 mg/day, respectively, and the number of affected glomeruli per 100 glomeruli 4.9 +/- 1.0 and 5.3 +/- 2.0, respectively. There were no significant differences in the urinary protein content, the number of the affected glomeruli, and immunofluorescence findings. In a control group, ACI/NMs rats exhibited 8.9 +/- 2.6 mg/day protein in urine and 0.8 +/- 0.4% affected glomeruli, which were significantly different from that of sham-operated and thymectomized BUF/Mna rats. These results indicate that nephropathy in BUF/Mna rats results neither from thymoma itself nor from the immunological abnormality secondary to it, and suggest that this lesion might be ascribed to a genetic factors. PMID- 3349651 TI - Elevated levels of the 26K human hybridoma growth factor (interleukin 6) in cerebrospinal fluid of patients with acute infection of the central nervous system. AB - We reported recently that a human protein, previously described as IL-1 inducible 26K factor (26K) or interferon-beta 2, was a potent growth factor for B cell hybridomas in vitro. Subsequently, it appeared that this protein was also identical with the lymphokine B cell stimulatory factor 2. Here we report that the levels of 26K are considerably increased during the early stages of acute infections of the central nervous system. This elevation in 26K titres was not observed in either chronic infections or in non-infectious diseases. PMID- 3349653 TI - Immunoglobulin profile of tracheal aspirate fluid in intubated children. AB - Pulmonary lavage immunoglobulins IgG, IgA and IgM were measured in intubated ventilated neonates during their period of intubation (range 1-64 days, mean 12). The neonates were divided into two groups based on gestational age (group 1 26-32 weeks, group 2 33-40 weeks). IgG levels were high at birth, and decreased exponentially throughout the period of intubation. There was no statistical difference in IgG levels between the two groups. IgA and IgM levels were low at birth, and increased linearly, there being a significantly greater increase with age in Group 2 (the more mature gestationally) for both immunoglobulins. Two groups of older children were also studied (2-4 year olds, and 8-10 year olds). In the 2-4 year age group, IgG levels were similar to those seen in the immediate newborn period, were quantitatively greater than IgA and IgM, and were not significantly different from levels in the 8-10 year olds. IgA and IgM levels were also not significantly different between the two groups. PMID- 3349654 TI - Oligoclonal and polyclonal synthesis of IgG in the central nervous system: an isoelectric focusing study. AB - The IgG pattern in isoelectric focusing (IEF) has been studied in 90 paired samples of cerebrospinal fluid (CSF) and sera obtained from patients in which intrathecal synthesis of IgG without barrier damage was detectable by Reiber's graph and formula (1980, J. Neurol. 224, 89). Thirty patients were affected by multiple sclerosis (MS), 30 by other inflammatory nervous diseases (OID), and 30 by noninflammatory nervous diseases (NID). At IEF two distinct pathological patterns of CSF IgG were detected: oligoclonal bands (OB), prevailing in the MS group (83% of cases), and a "polyclonal"--i.e., diffuse, uniform--increase of CSF IgG, prevailing in the NID (90%). The OID group was intermediate, 57% of cases with OB and 43% with polyclonal CSF IgG patterns. Overall, only 45 of 90 patients synthesizing IgG in the CNS had CSF OB. This suggests that the CNS immune response can imply either the synthesis of IgG of restricted heterogeneity (i.e., OB) or a polyclonal IgG synthesis, giving in IEF a serum-like pattern to the CSF. PMID- 3349655 TI - Analysis of human peripheral blood mononuclear cells bearing Fc receptors for the three major immunoglobulin isotypes. AB - Fluorochrome-labeled, human immunoglobulins (Igs) were used to characterize peripheral blood mononuclear cell (PBMC) subsets that had Fc receptors (FcRs) for the three major isotype classes, IgG, IgA and IgM. Relatively high concentrations of these Igs were needed to saturate FcRs. However, by a number of criteria, competition assays in particular, isotype-specific FcR binding was shown. In vivo bound Ig was directly measured by anti-Fc class-specific F(ab)2 antibodies. With the exception of monocytes, where a mean of 19% had in vivo bound IgG, only small percentages of other PBMC subsets had any type of in vivo bound Ig. Studies done on a large group of normal individuals revealed that approximately 27% of all PBMCs had gamma, 24% alpha, and 23% microFcRs. Dual fluorescence assays were performed to determine the gamma, alpha, and microFcR status on T, B, NK cells and on monocytes. The majority of staining for gamma, alpha, and microFcRs was accounted for by the numerically largest subfraction, the T cells. However, when FcR status was determined for each subset virtually all had either gamma, alpha, or microFcRs--94% of CD2+, 98% of CD4+, 73% of CD8+, 100% of CD19+, 100% of CDw19+, 92% of Leu 7+, and 61% of Leu 11+ cells. All three FcRs were expressed within each subset. Of interest, a small percentage of unfractionated and monocyte-depleted PBMCs coexpressed one of three pairs of FcRs, either alpha and gamma, alpha and mu, or mu and gamma. PMID- 3349656 TI - Inhibitory effect of lysozyme on the intraglomerular immune complex formation in lupus mice. AB - The effect of lysozyme on intraglomerular immune complex deposition was examined in NZB/W F1 mice undergoing unilateral nephrectomy. Unilateral nephrectomy enhanced the glomerular immune complex deposition and glomerular lesions, which were suppressed by repeated intraperitoneal injections of lysozyme, in spite of unaltered serum anti-DNA antibody titers. DNA binding to the glomerular basement membrane (GBM) examined in vitro and that to glomeruli examined in vitro were also suppressed by lysozyme. An increased survival rate and decreased proteinuria were also induced by this basic protein. The mechanisms of the ameliorative effect were studied in vitro. DNA was bound to the GBM only in the presence of serum, plasma, or fibronectin. A similar inhibitory effect on DNA binding was also obtained by another polycation, hexadimethrine, in place of lysozyme. The in vitro findings suggest that DNA binding to the GBM is mediated by fibronectin, and that lysozyme electrostatically inhibits this binding, thereby possibly reducing the in situ DNA-anti-DNA complex formation in the GBM. PMID- 3349657 TI - Extratubular Tamm-Horsfall protein deposits induced by ureteral obstruction in mice. AB - The effects of unilateral ureteral obstruction were studied in mice. Obstruction for 24 hr led to the formation of extratubular Tamm-Horsfall protein (TH) aggregates within the renal interstitium and at the base of distal convoluted tubular (DCT) cells. These DCT deposits were shown by ultrastructural analysis to be entirely extracellular. They had the fibrillar substructure characteristic of TH and had not been seen after urinary obstruction in other species. As a consequence of retrograde flow of urine to glomeruli, obstruction also caused TH aggregates to form within Bowman's spaces. These glomerular casts of TH were detected throughout the 3-week period of study after the release of unilateral obstruction. High serum titers of IgG antibodies to TH developed in mice intradermally immunized with TH but were not observed after obstruction alone. Circulating anti-TH antibodies combined with TH present on the basal surfaces of the thick ascending limb of the loop of Henle cells and DCT cells to form immune complexes in situ. Interstitial inflammation in the areas surrounding subepithelial tubular immune deposits was not present in the kidneys of immunized mice and was not selectively induced by temporary obstruction. However, foci of inflammation were seen in all obstructed kidneys. At later times, inflammatory foci in previously obstructed kidneys were associated with progressive scarring, primarily in polar regions. The location and severity of these changes within kidneys produced by obstruction in immunized mice did not differ from those in unimmunized mice. The titers of anti-TH antibodies in immunized mice were not enhanced or depressed as a consequence of unilateral ureteral obstruction. These studies demonstrate that complete obstruction of urinary flow in the mouse for periods as short as 24 hr may lead to progressive segmental renal scarring. These studies further indicate that increasing the quantities of extracellular TH by obstruction does not facilitate inflammatory responses to TH immune complexes formed in situ. While exposure of renal tissue to highly toxic components of extravasated urine may play a crucial role in inflammatory responses, autoimmunity to TH was not implicated as a contributing factor by the present studies in mice. PMID- 3349658 TI - Effect of ibopamine on the failing heart at rest and during isometric exercise: a noninvasive study. AB - Eleven patients suffering from heart failure were treated with oral ibopamine, a di-isobutyric ester of N-methyldopamine, 100 mg three times a day for 1 week and 200 mg three times a day for 3 weeks. Therapy was discontinued by one patient because of tachycardia. Left ventricular performance was evaluated with echocardiography and systolic time intervals at rest and after 3 minutes of isometric exercise using a handgrip. Six of 10 patients completing the study were in New York Heart Association (NYHA) functional class III, 2 in class IV, and 2 in class II. All patients, except one who remained stable in class II, improved their subjective condition by one functional class during 4 weeks of therapy (p less than 0.01). There were no changes in heart rate, blood pressure, rate pressure product, cardiac index, or total peripheral vascular resistance. The left ventricular end-systolic diameter decreased after four weeks from 71.2 +/- 12.7 (SD) to 65.9 +/- 13.0 mm (p less than 0.001); the left ventricular end diastolic diameter did not change. The ejection fraction increased from 26 +/- 8 to 32 +/- 9% (p less than 0.01). Afterload, that is, left ventricular circumferential systolic wall stress, declined as a result of decreased systolic diameter. Systolic time intervals did not vary. There were no changes due to ibopamine during isometric exercise probably owing to increased beta-adrenergic stimulation induced by the handgrip. Neither urine volume nor body weight changed. Side effects were mild except for tachycardia of one patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349659 TI - Is localization of acute myocardial infarction time related? AB - A total of 1744 patients admitted to the ICCU with acute myocardial infarction (AMI) were studied in 1462 consecutive days (1982-1986). The aim of the study was to check whether the localization of the AMI was time related. Anterior (anterolateral) (AW) (n = 834) versus inferior-posterior (inferolateral) (IPW) (n = 823) AMI were compared: a third group with isolated lateral wall (LW) AMI (n = 87) was included in the study. Significant differences between monthly AMI localizations were registered, but no rhythmicity (monthly, seasonal) was found. A small absolute prevalence of AW localizations was found in all four seasons, but monthly differences made those differences not statistically significant. Some significant correlation (p less than 0.01) was found between AW AMI domination and daily geomagnetic activity (GMA level I-IV). Only on days with low (quiet) levels of GMA were there more IPW AMIs. Adverse relationship was seen with LW AMI, relatively benign in AMI, was adversely correlated with GMA level (p less than 0.01). Differences in AW/IPW and left/right coronary artery autonomic receptors distribution and flow regulation and/or changes in cardiovascular homeostasis/coagulation, aggregation, viscosity, microcirculation, and so on connected with AMI expansion may be involved in these differences of AMI localization. PMID- 3349660 TI - Refractory swallowing-induced paroxysmal supraventricular tachycardia. AB - A 51-year-old female with a two-year history of palpitations associated with swallowing was evaluated by intracardiac electrophysiologic studies. Intracardiac recordings documented the presence of an ectopic left atrial focus induced by swallowing with no evidence of accessory pathway conduction. Gastrointestinal evaluation did not demonstrate any significant disorder. The tachycardia was refractory to all pharmacologic therapy including investigational therapy with mexiletine and amiodarone. PMID- 3349661 TI - Sinus arrest associated with clonidine therapy. AB - A 65-year-old male with diabetes, hypertension, and mild renal failure developed dizziness and syncope one week after starting clonidine 0.45 mg/day. A continuous ECG recording revealed sinus bradycardia, nodal rhythm, and multiple episodes of sinus arrest lasting up to 4.5 seconds. Upon discontinuation of clonidine, serial continuous ECG recordings revealed gradual decrease in the number and duration of the sinus arrest episodes, until their complete disappearance shortly after the third day off clonidine. This report shows that clonidine may cause a concentration-dependent sinus node dysfunction in addition to the atrioventricular (AV) node abnormalities previously ascribed to it. PMID- 3349662 TI - An infant with suspected right ventricular dysplasia presenting unique ventriculograms. AB - Angiocardiography was performed twice in a male infant at ten days after birth due to cyanosis during crying and at 4 years and 10 months of age for close examination of the heart prior to an operation for cerebral abscess. Outpouchings resembling multiple diverticula were observed in both ventricles, though more notably in the right ventricle, as well as slight enlargement and reduced ejection fraction of both ventricles. Evaluation of oxygen saturation indicated right-to-left shunt at the atrial level. Electrocardiography suggested a marked superior axis deviation, and chest roentgenography and two-dimensional echocardiography revealed enlargement of the right atrium and right ventricle. Soon after the examinations, the patient died suddenly during sleep at home. Since autopsy was not performed, a definitive diagnosis could not be made, but right ventricular dysplasia appeared likely. The unique angiocardiographic findings and clinical course of this rare patient are described. PMID- 3349663 TI - "Torsades de pointes" and atrioventricular block. AB - In order to elucidate the trigger factor of the production of torsades de pointes (TdP), electrophysiological study was conducted in 15 patients with atrioventricular (AV) block; 6 with TdP (TdP group) and 9 without TdP (control group). In the TdP group, all had an episode of syncope and frequent ventricular premature beats (VPBs) on routine ECG, while four (44%) had syncope and three (33%) had VPBs in the control group. Aging, QRS width, ventricular cycle length, QT interval, and block site from His bundle electrogram were similar in both groups, however the QTc interval was significantly (p less than 0.01) longer in the TdP group than in the control group (580 +/- 112 vs. 459 +/- 37, respectively). Furthermore, four patients (67%) in the TdP group showed advanced AV block in which a slow ventricular rate and an irregular rhythm were characteristic, whereas only one control (11%) showed advanced AV block and all other control patients (89%) had complete AV block. These data indicate that patients with advanced atrioventricular block associated with prolonged QTc interval and frequent ventricular premature beats might induce torsades de pointes. PMID- 3349664 TI - The influence of the ambient temperature on tumour growth, metastasis and survival in mice. AB - The effect of ambient temperature was analysed on the behaviour of MO4 cells which are malignant, invasive and metastasizing C3H mouse fibroblastic cells when implanted in the tail of the syngeneic animal. Raising the ambient temperature to 28 degrees C increases growth of the primary tumour, incidence of metastases and shortens survival. Lowering the ambient temperature to 13 degrees C prevents all these phenomena. Measurements at the implantation site show that the temperature of the tail remains in a range +/- 2-3 degrees C in accordance with the environment. From these results we conclude that room temperature may be important when experiments are performed in vivo. PMID- 3349667 TI - Antimetastatic action of orally administered lysozyme in mice bearing Lewis lung carcinoma. AB - The pharmacological activity of orally administered lysozyme, for the control of the growth of solid tumor metastases, was examined in mice bearing Lewis lung carcinoma. Groups of at least 10 tumor-bearing mice, fed daily for three consecutive weeks from subcutaneous tumor implantation with lysozyme, prepared from hen egg-white, had a pronounced reduction of the weight of their metastatic tumor to 25-50 per cent of controls within a wide range of doses (25-200 mg/kg/day). The antimetastatic effect was not related to the length of the treatment schedule employed; a short course of 7 days, given on days 1-7 after tumor implantation, proved equally active. The inhibition of the formation of lung metastases, in mice treated with lysozyme prior to tumor inoculation, lasts for at least 2 weeks after discontinuation of treatment, indicating that the antimetastatic activity observed is not associated with cytotoxic activity of the lysozyme, and is probably mediated by the elicitation of host responses. The examination of the therapeutic potential of the antimetastatic action of lysozyme supplied through the usual diet indicates that this treatment synergizes with the antitumor effects of cisplatin, given to mice after surgical removal of the primary tumor, causing a statistically significant prolongation of the survival time of the animals as compared with chemotherapy alone. PMID- 3349668 TI - Fractures of the femoral neck in elderly patients with hyperparathyroidism. AB - Five fractures of the femoral neck were observed in patients with primary or secondary hyperparathyroidism. In each case, the fracture line was vertically oriented near the base of the neck. The diagnosis was suggested by the patient's history and roentgenologic features and was confirmed by biochemical changes. None of the fractures healed despite internal fixation in four cases and appropriate treatment of the underlying disease. When such fractures occur in elderly patients, primary arthroplasty may be preferable to internal fixation. PMID- 3349666 TI - The growth and metastasis of four commonly used tumour lines implanted into eight different sites: evidence for site and tumour effects. AB - The growth and metastasis of four commonly used experimental tumour lines have been compared after the implantation of cells into a lobe of the liver, the spleen, the left kidney, the peritoneal cavity, the thorax, the right thigh muscle, subcutaneously into the dorsolumbar region and intravenously into the tail vein or the right femoral vein. This was done to assess the importance of site in affecting metastatic distribution, and to determine whether any general conclusions could be drawn as to the role of this factor. Tumours grew at variable rates in different sites, but this did not affect the extent or distribution of metastasis. Each line gave a characteristic pattern that could be considerably modified by site. For example, in the spleen, metastasis was always extensively to the liver; in the kidney, and to some extent in the muscle, metastasis was similar to that obtained for intravenously injected cells; in the peritoneal cavity or thorax, metastasis was usually lower than from other sites; and in the liver, the metastasis to other lobes of the liver and to the lungs was modified. Many of these findings could be explained by both specific and non specific factors operating at each site. It is suggested that interactions at the primary site of tumour growth may be very important in affecting metastasis, and that in the future more attention should be given to this factor in order to make progress in understanding tumour spread. PMID- 3349665 TI - Preferential growth of metastatic tumors at the pleural surface of mouse lung. AB - In an experimental model of lung metastasis we have observed that more metastatic tumors are located on the pleura of the lung than in the parenchyma. To study possible reasons for this differential pattern we have now related the initial distribution of injected tumor cells to the later location and growth rate of metastases in different regions of the lung in C57bl/6 mice. It was found that labeled murine fibrosarcoma cells were evenly distributed throughout the lungs 24 h after intravenous injection into controls and animals previously treated with bleomycin or by exposure to hyperoxia. These treatments, known to induce pulmonary endothelial injury, were associated with increased tumor cell localization in the lung. In all cases, using morphometric methods, we found that after 2 weeks, approximately 75 per cent of metastatic tumors were located at the pleura. By [3H]thymidine labeling in autoradiographs, pleural tumors in all experimental groups had a growth rate 14 times the growth rate of tumors located in the internal regions of the lung. In vitro, the fibrosarcoma cells proliferated more rapidly on connective tissue matrices prepared from normal pleuras than they did on matrices from the remainder of the lung. Protease digestion of these matrices indicated differences in composition with more insoluble collagen, probably type I collagen, present at the pleura. These data suggest that, in spite of the initial random distribution and localization of tumor cells in the lung, there is preferential growth of metastatic tumors at the pleura which may be related to regional differences in the composition of the extracellular matrix. PMID- 3349669 TI - Total femoral replacement. AB - Between 1973 and 1983, 19 patients with sarcoma of the femur were treated by adjuvant chemotherapy, excision of the entire femur, and replacement by a total femoral prosthesis. Five patients had excellent and nine had good functional results. Twelve patients died an average of 23 months after the procedure and seven are at present disease free. This limb-saving procedure permits rapid rehabilitation, prevents severe psychological problems, and improves the quality of life. PMID- 3349670 TI - The effect of centrifugation on the fatigue life of bone cement in the presence of surface irregularities. AB - Reduction of the porosity of bone cement by centrifugation significantly improves the fatigue life of the cement when smooth, waisted specimens are tested. However, bone cement in vivo has surface irregularities at the interdigitation of the cement with the trabecular bone. The effect of centrifugation on the fatigue life of Simplex P in specimens containing surface irregularities was investigated by examining both composite specimens of trabecular bone and bone cement and specimens containing a sharp, circumferential notch. For the specimens with the sharp notch, the bone cement that had been centrifuged lasted significantly longer in fatigue (47,039 +/- 40,277 cycles) than the uncentrifuged specimens (3103 +/- 1950 cycles). Eleven of 15 uncentrifuged specimens broke at the location of a void, rather than the notch. In contrast, when the porosity was reduced by centrifugation, 13 of the 15 specimens broke at the notch. For the specimens that were a composite of bone cement and trabecular bone, the centrifuged specimens had a significant increase in fatigue life compared to the uncentrifuged specimens when tested at both 7 MPA (641,056 +/- 444,131 cycles vs. 237,969 +/- 124,153 cycles) and 15 MPA (8800 +/- 4673 cycles vs. 1534 +/- 719 cycles). Reduction of porosity in bone cement by centrifugation significantly extends its fatigue life even in the presence of trabecular bone or sharp surface notches as used in total joint replacements. These data support the concept that reduction of porosity of bone cement by centrifugation may extend the duration of fixation of the components in cemented total joint arthroplasties. PMID- 3349671 TI - Closed flexible intramedullary biopsy of metastatic carcinoma. AB - Closed flexible intramedullary biopsy was performed in 24 patients requiring surgical stabilization of 17 pathologic and ten impending pathologic fractures from metastatic carcinoma. The biopsy was positive for carcinoma in 25 of 27 cases and either confirmed the diagnosis of metastatic disease or revealed a carcinoma cell type of unknown origin. The technique of closed biopsy using an intramedullary flexible, large bore, plastic catheter in patients with metastatic carcinoma produced information comparable to other biopsy techniques. PMID- 3349672 TI - Revision operations on infected total hip arthroplasties. Two- to nine-year follow-up study. AB - One hundred two of 110 infected hip arthroplasties revised with the protection of gentamicin-loaded cement were followed for a minimum of two years. In 77 of 102 hips the infection healed after one revision operation and in five of eight hips after a second revision operation, representing a final healing rate of 80%. No significant difference in healing rate could be demonstrated with regard to individual bacterial species. However, in infections with a mixed flora, the healing rate was only 27% (p less than .01). After an average of six years, 33 of 82 healed hips had signs of roentgenographic loosening, nine of which had been revised. The modified Merle d'Aubigne and Postel score averaged 5.3 for pain, 3.7 for walking ability, and 4.0 for range of motion (ROM) in patients with healed infections. PMID- 3349673 TI - Clinical features of pseudogout attack. A survey of 50 cases. AB - Fifty patients (15 men and 35 women; average age, 70.8 years) with pseudogout were studied. Arthroscopic biopsy was useful for diagnosis in one case with no light microscopic evidence of crystals in the synovial fluid. Attacks affected 93 sites in 50 patients. Attacks in ten patients occurred after mild trauma, long distance walks, total knee arthroplasty, or intraarticular injection of microcrystalline glucocorticoid. Twenty-five patients had fevers averaging 38 degrees. In five patients the fever was associated with mental confusion. Fourteen patients were initially suspected or misdiagnosed as having septic arthritis. Six patients were treated surgically under this misdiagnosis, with synovectomy complicated by limitation of motion of both knees in one patient. The involvement of more than one joint was noted in 21 patients. Polyarthritis could be an important clue to the diagnosis performed early; the combination of arthrocentesis and injection of microcrystalline glucocorticoid provided excellent therapy. PMID- 3349675 TI - The role of arthroscopy in the treatment of postoperative fibroarthrosis of the knee joint. AB - Twenty-one patients with significantly limited range of motion of the knee secondary to open surgical procedures were treated by arthroscopic resection of the adhesions and gentle manipulation. The surgical procedures consisted of realignment procedures for patellar dislocation, arthrotomy for meniscectomy and synovectomy, ligamentous reconstruction, open reduction of intraarticular fractures, and prosthetic replacement. The interval between the arthroscopic treatment and the open procedures was from four months to two years. All patients had the arthroscopic releases performed with general or spinal anesthesia, were kept in the hospital for a minimum of three days, and were placed on a continuous passive motion machine. After discharge, an intensive rehabilitation program was instituted under the supervision of a physical therapist. With a follow-up period ranging from six months to two years, marked improvement of range of motion was obtained in most patients. Preoperative flexion was between 40 degrees and 50 degrees in 13 patients, 30 degrees in two patients, 60 degrees in four patients, 80 degrees in one patient, and 10 degrees in only one patient. The final flexion was between 120 degrees and 140 degrees in 12 patients. The remaining patients had postoperative flexion between 85 degrees and 100 degrees. One patient with 10 degrees of range of motion did not improve. Six of the eight patients with an extension lag preoperatively regained full or almost full extension after arthroscopic debridement. Morbidity was low and no serious complications were encountered. This study suggests that arthroscopic intraarticular release of adhesions is efficacious in the management of arthrofibrosis of the knee subsequent to previous open operative procedures. PMID- 3349674 TI - Serum lidocaine levels during arthroscopy using continuous irrigation with lidocaine. AB - Forty patients with symptoms of internal derangement of the knee were examined arthroscopically under local anesthesia using a continuous irrigation solution of 0.2% lidocaine. Serum levels were measured during and following the procedure to determine peak levels obtained and to assure that toxic levels were not exceeded. The procedure was well tolerated by all patients and found to be adequate by the surgeon. No procedure was terminated because of discomfort. Lidocaine levels ranged from undetectable to 2.5 micrograms/ml with an average of 0.6 microgram/ml. No complications of lidocaine toxicity were noted by the anesthesiologist or the operating surgeon. This technique provides a safe and efficient method of meeting the demands for diagnostic and therapeutic arthroscopy in ambulatory patients. PMID- 3349677 TI - An operation for progressive spinal deformities. PMID- 3349676 TI - Proximal tibial osteotomy. Factors that influence the duration of satisfactory function. AB - Survival analysis studies of 40 patients treated with high tibial osteotomy for arthritis with angular deformity were performed to determine the dominant factors that adversely affected long-term knee function. Obesity, advanced age, and postoperative overcorrection or undercorrection resulted in short durations of successful function. On the average, the probabilities for continued useful function of the knee at tested intervals were: one year, 86%; three years, 64%; five years, 50%; and nine years, 28%. PMID- 3349679 TI - Micromotion of noncemented Freeman-Samuelson knee prostheses in gonarthrosis. A roentgen-stereophotogrammetric analysis of eight successful cases. AB - Micromotion of the tibial component of eight Freeman-Samuelson arthroplasties without cement for gonarthrosis were followed for two years and studied by roentgen-stereophotogrammetric analysis (RSA). In five cases, displacement over time was studied, and in all cases migration was found to range from 0.7 to 4.8 mm after two years. One tibial component migrated continuously during the period studied, while the remaining prostheses migrated mostly during the first six months. The direction of the migration was erratic. Inducible displacement ranging from 0.8 to 5.0 mm was found in all cases. Clinically, all of the patients were scored as successful although one with continuous migration had the lowest score. This degree of micromotion is compatible with good results after two years, and appears to be a characteristic of the immediate interlocking fixation used in the Freeman-Samuelson prosthesis. PMID- 3349678 TI - Steroid-induced osteonecrosis of the patella. AB - Two cases of previously unreported steroid-induced osteonecrosis of the patella were investigated. The first case was a 46-year-old man who had been receiving steroid therapy for three years for treatment of bronchial asthma. The second was a 32-year-old woman who had been receiving steroid therapy for nine years as treatment of systemic lupus erythematosus. Both reported slight knee pain. The roentgenographic findings revealed increased radiodensity with radiolucency of the upper one-half of the patella. A trephine biopsy revealed focal areas of dead trabecular bone. PMID- 3349680 TI - Supracondylar fractures of the femur adjacent to resurfacing and MacIntosh arthroplasties of the knee in patients with rheumatoid arthritis. AB - Twelve cases of supracondylar fracture of the femur in rheumatoid arthritis patients with previously implanted resurfacing or MacIntosh arthroplasty of the knee had long standing severe polyarticular rheumatoid arthritis (duration, ten to 41 years; mean 24.8 years). The fractures occurred following a long interval after implantation of the prosthesis (five to 204 months; mean, 92.3 months). Two fractures were treated by stable and two by unstable fixation; eight were treated nonoperatively. The fractures healed in a normal time with one exception, but the femur was shortened in ten cases (mean, 2.8 cm), and axially malaligned in nine. The ability to walk long distances decreased in eight cases and pain increased in seven; two prostheses were loosened and displaced. Because of the poor results of nonoperative management, internal fixation of these fractures is recommended in selected cases. PMID- 3349681 TI - Surgical interruption of patellar blood supply by total knee arthroplasty. AB - Arterial blood supply of the patella was demonstrated in 21 cadaver knees by intraarterial injection of radiopaque contrast. When the standard medial parapatellar approach or lateral retinacular release was carried out at a distance of at least 1 cm from the margin of the patella, some steps in total knee arthroplasty caused no impairment and others jeopardized the filling of intraosseous vessels. The radial intraosseous vessels are jeopardized by osteotomy of a deformed patella or excision of fat pad. The prepatellar vessels greatly contribute to intraosseous vascularization and should be carefully preserved. PMID- 3349682 TI - Simultaneous bilateral avulsion fracture of the tibial tuberosity. A case report. AB - Bilateral avulsion fracture of the tibial tuberosity is a rare injury. A 14-year old male gymnast sustained simultaneous tibial tuberosity displaced fractures while attempting a forward flip. The recommended treatment was open reduction and internal fixation. Functional results were excellent one year after surgical treatment. PMID- 3349683 TI - Psychologic testing in amputation rehabilitation. AB - Sixty adult patients had psychologic testing following successful below- or above knee amputation surgery. All were considered to be prosthetic candidates based on the evaluation of an experienced multidisciplinary rehabilitation team. Objective psychologic testing revealed that six (10%) had severe deficits in cognitive ability, eight (13%) had covert psychiatric illness, and three (5%) had both. A vigorous attempt at prosthetic limb fitting and gait training was made in every patient in an inpatient rehabilitation unit. Of the 17 patients (28%) who were determined to be poor candidates for prosthetic limb fitting and gait training based on objective psychologic testing, only four (6%) were capable of even minimal use of the prosthesis, and none approached their preamputation level of ambulation. Psychologic testing may play an important role in determining the rehabilitation potential of the dysvascular amputee. PMID- 3349684 TI - Isobutyl cyanoacrylate as a soft tissue adhesive. An in vitro study in the rabbit Achilles tendon. AB - Cyanoacrylates (CAs) are biodegradable, bacteriostatic, and hemostatic adhesives. CAs have been used in medical applications, but with adverse effects, including excessive inflammatory reaction and neural toxicity. Isobutyl CA (ICA) appears more biocompatible, with a long half-life that may be ideal for a soft tissue adhesive. The rabbit Achilles tendon was chosen to test (ICA), and a special muscle-freezing clamp to test this model was designed. The tendons were sharply cut 2 cm proximal to their insertion and repaired in four groups. They were tested to failure on an Instron machine. The breaking strength of the repairs was then noted. Also, the breaking strength of several suture materials was tested. Four Achilles tendon repair groups were evaluated: ICA alone 9.03 newtons (NTS); 4-0 silk Kessler stitch, mean 12.9 NTS; Kessler stitch plus three simple stitches, mean 23.0 NTS; and a combination of (a) and (c)--i.e., suture and adhesive, mean 40.2 NTS. The intact Achilles tendon was tested with an average breaking strength of 317 NTS. The muscle-freezing clamp facilitated reasonable testing of this tendon repair. ICA alone exhibits reasonable strength in vitro and in combination with suture provides a stronger initial repair than either suture or adhesive alone. PMID- 3349685 TI - Screening school children for scoliosis. AB - Idiopathic scoliosis can be detected by early screening of school children in school clinics, a method which improves the detection rate. By early detection, many curves that would require surgical treatment can be prevented from reaching that severe magnitude. Much valuable data regarding the natural history of idiopathic scoliosis have been derived from screening programs. On the other hand, costs of screening are not inconsequential, and costs involved in follow-up procedures are high. Vast numbers of small, nonprogressive curves are discovered and followed. Several questions remain. (1) At what ages should school children be screened? (2) Should boys be screened? (3) What should be the criteria for referral or treatment? (4) What is a reasonable follow-up program? (5) How effective is nonoperative treatment? Careful study of the natural history and treatment of idiopathic scoliosis will help to answer these questions. PMID- 3349686 TI - A study of ligamentous growth. AB - Scant data are available on the growth of ligament. This study answers basic questions concerning mechanisms of ligament growth and determines the location of longitudinal ligament growth. Growing rabbits had metal marking sutures implanted, at measured intervals, along the length of their medial collateral ligament. Separate metal markers were inserted in the epiphysis and metaphysis of the femur and tibia. Changes in marker intervals were measured radiographically after growth. Measurements revealed that growth occurred throughout the length of the ligament, with somewhat greater growth occurring in the distal segment. Total ligament growth was much less than that occurring at the tibial physis (which the ligament crosses). The magnitude of total ligament growth was proportional to the enlargement of the joint itself, as measured by changes in the distance between epiphyseal markers. The most distal suture inserted in the ligament became incorporated in bone and moved rapidly away from the ligament insertion. This rapid displacement of the distal suture was not responsible for enlargement of the ligament itself, but rather a phenomenon of the maintenance of the position of the ligament insertion on the proximal metaphysis, as the epiphysis grows away from the original site of ligament insertion. PMID- 3349687 TI - The effect of immobilization on goat knees following reconstruction of the anterior cruciate ligament. AB - Significant patellofemoral chondromalacia was observed three months after operations on goat knees that had an excised anterior cruciate ligament (ACL) replaced and then were immobilized for six weeks with a rigid external pin and frame fixator. To determine if the patellofemoral morbidity rate could be reduced, another group of goats was treated with the same operation but without immobilization. The legs of the animals in the immobilized group had muscle weakness and the animals only occasionally used their legs for the next three to four weeks. The animals in the mobilized group protected the leg for only one to two days after surgery, and by ten to 12 days were actively moving the knee. Severe patellofemoral articular cartilage erosions occurred in the immobilized goats but not in the mobilized group. Postoperative immobilization was detrimental to the joint function and to a successful ACL reconstruction. PMID- 3349688 TI - Colloidal chromic phosphate 32P synovectomy in antigen-induced arthritis in the rabbit. AB - Radioisotopes have been employed in the therapy of chronic arthritis, in particular, rheumatoid arthritis for many years. A variety of isotopes have been popularized, and in the last ten years a colloidal solution of radioactive chromic phosphate 32P has been in use apparently with equivalent efficacy to others such as 169erbium, 90yttrium, and 165dysprosium. No controlled studies on this modality have been reported and few animal studies were found. The efficacy of therapeutic doses of 32P as a medical synovectomy and its effect on rabbit joints with antigen-induced arthritis were observed in 62 arthritic knee joints in 31 adult rabbits treated on one side with 0.1 microCi of 32P, the opposite serving as control. The animals were observed over a period of 11 months and examined by histologic and biochemical means. The synovium showed no evidence of radiation necrosis in treated joints. Cartilage of treated and control joints showed similar changes consistent with chronic arthritis, persistent synovitis, progressive chondrocyte degeneration, and decreased matrix metachromasia. The radiosynovectomy had neither removed synovium nor protected the cartilage. Its efficacy in humans is therefore questionable. PMID- 3349689 TI - Distribution pattern of the deep branch of the ulnar nerve in the hypothenar eminence. AB - The deep branch of the ulnar nerve (DBUN) was carefully dissected, using gross and microtechniques, in 21 fresh frozen cadaver upper extremities. This study emphasized branching patterns of the DBUN to the hypothenar muscles and the interrelationship of variations in hypothenar muscle anatomy and DBUN branching patterns. The DBUN generally passed between the abductor digiti minimi and the flexor digiti minimi, and then through the interval between superficial and deep layers of the opponens digiti minimi on its course to the deep palm. Innervation of the hypothenar muscles was by one to four branches of the DBUN. The most common distribution pattern was two major branches, which occurred in 14 (66%) of the specimens. Of these 14 specimens, nine exhibited normal hypothenar muscle anatomy, suggesting a prevalent relationship between three normal muscles and two nerve branches. One main branch occurred in four (19%) specimens, three branches occurred in two (9%) specimens, and four branches occurred in one (4%) specimen. Anatomic variations in the hypothenar muscles were significant, the most notable being the absence of flexor digiti minimi in eight (38%) of the specimens. PMID- 3349690 TI - Mechanical disruption of human patellar cartilage by repetitive loading in vitro. AB - Plugs of cartilage and subchondral bone from patellae were subjected to cyclic compression consisting of rapid ramp loading for 0.3 seconds followed by a 2.7 second pause. At 1000 psi cyclic load, surface abrasion of the cartilage was noted at 250 cycles of compression. Primary fissures, which penetrated to the calcified cartilage, developed at 500 cycles. Secondary fissures, emanating from the primary fissures at 30 degrees-90 degrees angles, and penetrating to varying depths, were observed at 1000 cycles. Coalescence of fissures and undermining of cartilage fragments were noted at 8000 cycles. With greater loads, the same sequence of events occurred with fewer cycles except that primary fissures appeared before the surface was abraided. Fissure formation did not occur in specimens subjected to loads of 250 psi to 500 psi even if the superficial 100 micron of cartilage was removed and specimens were loaded for 120,860 cycles. The deeper layers of cartilage appear to be of prime importance in resisting fissure formation. PMID- 3349691 TI - Early mobilization of adolescent scoliosis patients following Wisconsin interspinous segmental instrumentation as an adjunct to Harrington distraction instrumentation. Preliminary report. AB - This is a preliminary report of the authors' first 40 patients treated by posterior spinal fusion with Wisconsin interspinous segmental instrumentation (WISSI) with a minimum 18-month follow-up period. No major complications because of the instrumentation were encountered. The patients were allowed to sit in a chair on the second or third postoperative day. Early elimination of postoperative casts resulted in an increased rate of problems with fixation and led to reintroduction of a postoperative orthosis, but not the body cast. Some fixation problems may have been related to technical errors and use of the earlier one-button technique. In two patients who had hook dislodgement, the WISSI maintained spinal correction thereby demonstrating its stabilizing effect. PMID- 3349692 TI - Intraoperative somatosensory evoked potential monitoring in scoliosis. AB - During surgical correction of scoliosis, 63 patients had somatosensory evoked potential (SEP) monitoring of the spinal cord. Tibial nerves were unilaterally stimulated, and the potentials were recorded from the midcervical spine with surface and epidural needle electrodes. Over 85% had no significant change in their SEP and no postoperative neurologic deficits. Eleven percent had a significant change in their potential (amplitude decrease of greater than 60% and/or latency increase of greater than 2.5 msec) with no neurologic complications. One patient had a significant potential change and temporary postoperative sensory deficits did occur. One additional patient experienced postoperative neurologic complications but had no SEP change. This single false negative case, however, was clinically significant only for motor dysfunction, which is not monitored by the SEP. When changes in patient core temperature were compared to changes in SEP amplitude and latency, an intraoperative decrease in core temperature increased SEP latency and decreased amplitude, which may explain in part the false positive rate of the procedure. PMID- 3349693 TI - Hepatic uptake of technetium-99m diisopropyl iminodiacetic acid (DISIDA) is not impaired by very high serum bilirubin levels. AB - The hepatic clearance of Tc-99m labeled iminodiacetic acid (IDA) compounds is believed to be impaired in patients with severe hyperbilirubinemia. Competitive inhibition of hepatocyte uptake of IDA by bilirubin has been demonstrated in vitro, but not by clinical scintigraphy. We present a patient with Crigler-Najjar syndrome without evidence of hepatobiliary damage, who demonstrated normal uptake and excretion of Tc-99m DISIDA despite a serum indirect bilirubin level in excess of 30 mg/dl. It is therefore suggested that a markedly elevated serum bilirubin level per se does not inhibit hepatic uptake of Tc-IDA and does not preclude clinically useful scintigraphic examination. PMID- 3349694 TI - The negative radionuclide venogram: an indication for conservative therapy? AB - A retrospective study of 51 patients with a negative lower extremity radionuclide venogram and a 6-month follow-up was performed. None of the patients received anticoagulation. Fifty of the 51 patients had no subsequent symptoms nor signs suggesting undiagnosed deep venous thrombosis or pulmonary emboli. On reviewing the radionuclide venogram of the one patient who returned with persistent symptoms and signs of deep venous thrombosis, it was found that the initial radionuclide venogram was misinterpreted. These findings suggest that a negative radionuclide venogram, properly performed and interpreted, implies the absence of clinically significant deep venous thrombosis. PMID- 3349695 TI - Detection of an ileal cavernous hemangioma by technetium-99m red blood cell imaging. AB - Patients with arteriovenous malformations of the bowel may have multiple symptoms secondary to chronic blood loss. A case of ileal cavernous hemangioma detected by Tc-99m labeled red blood cell imaging in the absence of active gastrointestinal bleeding is presented. PMID- 3349696 TI - Malunion of a femoral fracture mimicking osteomyelitis in three phase bone imaging. AB - A case of greatly increased blood flow in the region of a fracture with malunion of the left femur, both in the flow and immediate blood pool studies during three phase bone imaging, is presented. The sluggish left femoral artery flow resulted from the greatly increased regional perfusion and is similar to the findings in acute osteomyelitis. The sluggish left femoral artery flow and greatly increased regional perfusion of the site is probably best explained as a regional "neurovascular flush" resulting from the pain caused by the malunion of the fracture and/or hyperemia in the area of the malunion responding to inflammation. PMID- 3349697 TI - Clinical efficacy of intravenous morphine administration in hepatobiliary imaging for acute cholecystitis. AB - The most urgent diagnosis addressed by cholescintigraphy is acute cholecystitis. By administering low-dose intravenous morphine sulfate to patients undergoing cholescintigraphy (who demonstrate visualization of both the common bile duct and intestine and nonvisualization of the gallbladder), the time required to complete the study has been reduced to a maximum of 90 minutes. One hundred twenty-eight patients underwent cholescintigraphy for clinically suspected acute cholecystitis. Forty patients received intravenous morphine sulfate during the procedure. In patients who received morphine sulfate during the examination, the sensitivity of cholescintigraphy for the diagnosis of acute cholecystitis was 100%; the specificity was 85%. PMID- 3349698 TI - Gallium-67 pulmonary uptake in eosinophilic pneumonia. AB - Eosinophilic pneumonia is usually diagnosed based on the findings on chest x-ray, white blood count, and transbronchial biopsy. After reporting a case of Ga-67 lung uptake in eosinophilic pneumonia, its histopathology is discussed and the mechanisms of Ga-67 uptake by inflammatory lesions are reviewed. PMID- 3349699 TI - Polymorphonuclear leukocytes labeled with technetium-99m HMPAO. A potential bone marrow imaging agent. AB - A case of multifocal avascular necrosis of the bone complicating systemic lupus erythematosis is presented in which the extent of involvement was incidentally identified by Tc-99m HMPAO leukocyte imaging. Leukocytes labeled with Tc-99m HMPAO may be an excellent bone marrow imaging agent. PMID- 3349700 TI - Correlation between iodine-131 MIBG imaging and biological markers in advanced neuroblastoma. AB - I-131 metaiodobenzylguanidine (MIBG) imaging was performed in 38 patients with advanced neuroblastoma. Abnormal images were found in patients with elevations of urinary vanillylmandelic acid and dopamine and high serum neuron-specific enolase levels. Normal or minimal elevation of markers was seen in patients with negative images. In follow-up studies after chemotherapy, the disappearance of abnormal uptake was noted in those patients with normal marker values. A persistently abnormal uptake occurred in patients with high marker values. Conversion from a normal image to an abnormal image also occurred in patients whose markers became elevated. I-131 MIBG imaging is sensitive in detecting active foci of a neuroblastoma and is useful in monitoring chemotherapy in these patients. PMID- 3349701 TI - Increased accumulation of N-isopropyl-(I-123) p-iodoamphetamine in the left auditory area in a schizophrenic patient with auditory hallucinations. AB - A schizophrenic patient with auditory hallucinations is reported in which IMP markedly accumulated in the left superior temporal and inferior parietal lobes which correspond to the left primary and secondary cortical auditory areas and angular gyrus, respectively. PMID- 3349702 TI - Technetium-99m glucoheptonate imaging: meningocele. PMID- 3349703 TI - Demonstration of a para-aortic hematoma with indium-111 labeled leukocytes after translumbar angiography. PMID- 3349705 TI - Hunter's shoulder in bone imaging. PMID- 3349704 TI - Anomalous insertion of the right hepatic duct into the cystic duct demonstrated by hepatobiliary imaging. PMID- 3349706 TI - Unusual liver configuration secondary to radiation therapy in childhood. PMID- 3349707 TI - Wandering spleen. The use of decubitus views during hepatic imaging. PMID- 3349708 TI - False-positive calvarial uptake of indium-111 leukocytes in a patient with hyperostosis frontalis interna. PMID- 3349709 TI - Value of single photon absorptiometry in osteoporosis screening. AB - Radial bone mineral content and bone mineral density were measured in 1515 women referred for osteoporosis screening. A detailed questionnaire allowed the selection of 1069 normal white women for further analysis who had no historical evidence of bone disease or predisposing factors for bone disease. The nondominant radius was measured at two locations: the midradial bone density (MRBD) composed of predominantly cortical bone and the distal radial bone density at the 5 mm site (DRBD) composed of a mixture of cortical and trabecular bone. Women considered at risk were defined as those whose bone density values fell below fracture risk levels (0.550 g/cm2 for the MRBD and 0.325 g/cm2 for the DRBD). Between the ages of 20 and 70 years, the DRBD showed significantly greater sensitivity in defining subjects at risk (N = 223) than than MRBD (N = 80); P less than 0.001. Analysis of all ages showed that 684 women were above the fracture risk value (FRV) at both sites (64.0%), 260 were below the FRV at the DRBD 5 mm site (24.3%), 14 were below the FRV at the MRBD site (1.3%), and 111 were below the FRV at both sites (10.4%). Postmenopausal women age 50 to 70 years receiving estrogen replacement therapy (N = 221) had significantly higher values at both sites (P less than 0.001) than age-matched postmenopausal women not receiving replacement therapy (N = 239). Hereditary factors significantly correlated with both sites but neither site showed that calcium intake, activity level, or cigarette smoking were significant variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349710 TI - Discordant uptake of technetium-99m DISIDA and technetium-99m sulfur colloid in an amebic abscess. AB - Hepatobiliary imaging in a patient with an amebic abscess showed an early cold defect that later showed rim enhancement. A Tc-99m SC scan did not show prominent flow (making hepatoma unlikely) and showed the previously noted defect to appear larger and without rim enhancement. The differential damage to Kupffer cells and hepatocytes or edema may account for these findings. Amebic abscess should be included in the differential diagnosis of lesions that give increased Tc-99m IDA but cold Tc-99m SC images. PMID- 3349711 TI - Coexistence of a nonfunctioning thyroid nodule in Plummer's disease demonstrated by thallium-201 imaging. AB - A patient with Plummer's disease in whom a coexisting nonfunctioning thyroid nodule was detected by TI-201 imaging is presented. I-123 imaging revealed a hot nodule corresponding to the functioning nodule and little uptake in the rest of the thyroid. In contrast, two areas of abnormalities were noted on a TI-201 image: one corresponded to the hot nodule in I-123 imaging and the other was visualized in the suppressed part of the thyroid in the same lobe. This case revealed that TI-201 imaging is clinically useful in detecting coexisting nodules in the suppressed part of the thyroid. PMID- 3349712 TI - Right ventricular infarction in tetralogy of Fallot. Thallium myocardial imaging. PMID- 3349713 TI - Serendipitous detection of intrarenal abscesses on technetium-99m MDP imaging while evaluating a foot ulcer. PMID- 3349714 TI - Inguinal hernia demonstrated incidentally during bone imaging. PMID- 3349715 TI - Scintigraphic demonstration of an ectopic parathyroid adenoma. PMID- 3349716 TI - Hepatic hemangioma. Unexpected bone scan finding. PMID- 3349717 TI - Mucocele of the skull. PMID- 3349718 TI - Unresolved major pulmonary embolism. Long-term scintigraphic follow-up. PMID- 3349719 TI - Localization of a skeletal imaging agent in nonmalignant ascites. PMID- 3349720 TI - Simultaneous measurement of ventricular function and myocardial perfusion using the technetium-99m isonitriles. AB - To assess both ventricular function and myocardial perfusion, five normal volunteers, 19 patients with coronary artery disease, and two patients with cardiomyopathy and normal coronary arteries were injected with 20 mCi of Tc-99m isonitrile (either methoxyisobutyl isonitrile or carbomethoxyisopropyl isonitrile) at peak bicycle exercise and again at rest. A standard Tl-201 stress test was performed in all patients at the same level of exercise within one month of the isonitrile study. In all normal subjects, myocardial perfusion was normal at stress levels and the left ventricular ejection fraction increased 5% or more with exercise. In the 19 patients with coronary artery disease, the ejection fraction response to exercise was abnormal in 14 patients. Perfusion images with the Tc-99m isonitriles correlated well with Tl-201 images during exercise and at rest, with 89% concordance in areas of ischemia or infarction and 93% in normal segments. A simultaneous study of myocardial perfusion and ventricular function can be performed using a single Tc-99m labeled myocardial agent. Tc-99m isonitriles, particularly Tc-99m MIBI, result in sufficiently high photon flux that ventricular performance can be studied at peak exercise and again during rest using the first pass method. PMID- 3349721 TI - Radionuclide bone imaging findings in loose cemented joint prostheses appear to be normal postoperative findings in cementless joint prostheses. Preliminary case report. AB - Two cases exemplify that three point uptake on radionuclide bone scans within the first postsurgical year of press-fit cementless joint prostheses appear to be a normal physiomechanical finding. PMID- 3349722 TI - Calf muscle arteriovenous malformations detected by technetium-99m erythrocyte venography. AB - Two cases of calf muscle arteriovenous malformation in young women, presenting clinically as deep venous thrombosis, were initially detected by Tc-99m erythrocyte venography and later confirmed by arteriography. The role of this technique in the investigation of venous thrombosis is discussed, emphasizing the importance of the lateral calf view. PMID- 3349723 TI - Chondromalacia of the patella. Bone imaging correlated with arthroscopic findings. AB - One hundred adult sports medicine patients with clinical findings suggesting chondromalacia of the patella underwent bone imaging. Of these patients, 50 eventually underwent arthroscopic surgery and the remaining 50 were treated conservatively. The intensity of abnormally increased scintigraphic activity in the patella correlated closely with the grade of chondromalacia observed by the arthroscopist. Bone imaging also was of value in directing the arthroscopist to clinically unsuspected torn menisci. In conclusion, for sports medicine patients with clinical findings suggestive of chondromalacia of the patella, bone imaging contributes to an accurate diagnosis and appropriate surgical planning. PMID- 3349724 TI - Pleuroperitoneal communication in a patient with right pleural effusion and ascites diagnosed by technetium-99m sulfur colloid imaging. AB - A 55-year-old man with an 11-year history of intermittent right pleural effusions had continued fevers and a large right transudative pleural effusion. Minimal ascites was noted by ultrasound examination. A communication between the thorax and intraperitoneal cavity was established by radionuclide examination of the chest and abdomen. Tc-99m sulfur colloid was injected into the peritoneal cavity, and imaging at 1 and 4.5 hours confirmed passage from the peritoneal to the pleural cavity. Repeated attempts to sclerose the pleural cavity failed to decrease the transudative accumulations. The patient was subsequently treated with the placement of a LeVeen shunt. PMID- 3349726 TI - Autologous blood transfusion in a pediatric population. Safety and efficacy. AB - A program for both preoperative collection and intraoperative salvage of autologous blood was established for a pediatric population. Eighty two patients, 16 years old or younger, participated during a 2-year period. Thirty four had blood collected preoperatively and 48 utilized salvaged blood only. Only 5 percent of preoperative donations were associated with any adverse reaction and all reactions were mild. Salvaged blood provided an average of 48 percent of all blood needs in those patients in whom it was used alone; in only 10 percent of cases did it provide for all of the patient's blood needs. Preoperatively collected blood met an average of 74 percent of blood needs when it was used alone; in half of the cases it was the only blood the patient required. The combination of preoperatively collected and intraoperative salvaged blood was highly successful, meeting an average of 94 percent of blood needs and supplying all blood needs in 77 percent of these patients. PMID- 3349725 TI - Population analysis of the pharmacokinetic variability of high-dose metoclopramide in cancer patients. AB - Metoclopramide infusions are used to prevent nausea and vomiting in cancer patients during chemotherapy. 47 patients received metoclopramide during 109 chemotherapeutic treatments as a loading (dose range = 0.55 to 4.5 mg/kg over 15 minutes) and maintenance (dose range = 0.57 to 4.8 mg/kg over 8 hours) infusion. During and up to 24 hours after the end of the maintenance infusion between 4 and 10 blood samples were collected per treatment. Metoclopramide was analysed in plasma by liquid chromatography. Pharmacokinetic and demographic data of 83 treatments were analysed by the NONMEM program using a linear 2-compartment model. It was found that bodyweight and serum alkaline phosphatase activity explain some of the interindividual variability in clearance (CL). The typical pharmacokinetic parameters for an average individual (70kg, alkaline phosphatase = 100 IU/L) were: CL = 20 L/h; volume of distribution at steady state (Vdss) = 190L; terminal half-life = 8h. The interindividual variabilities in clearance, volume of central compartment and Vdss were 50%, 35% and 35%, respectively. The residual variability in plasma concentrations was estimated as 13%. PMID- 3349728 TI - Breast milk jaundice in preterm infants. AB - A retrospective study was performed comparing bilirubin levels in 40 preterm newborns with uncomplicated courses fed a combination of premature breast milk and formula to those of 60 comparable preterm newborns fed formula only. A significantly higher bilirubin level was noted in the group fed the combined diet on the 6th day of life and on the day of discharge. Seventy-six and seven tenths percent of the preterm infants fed breast milk and formula met the criteria for phototherapy, whereas only 45 percent were treated in the group fed formula alone. Our findings indicate that premature breast milk might cause early and late increase in bilirubin levels in healthy preterm newborns. PMID- 3349729 TI - Bacterial meningitis in children whose cerebrospinal fluid contains polymorphonuclear leukocytes without pleocytosis. AB - A retrospective study was performed of 424 children who received diagnostic lumbar puncture for analysis of cerebrospinal fluid during evaluation of an acute illness. In 106 children, the CSF contained polymorphonuclear leukocytes without pleocytosis. Of these 106 patients, 90 percent had a CSF differential cell count with 20 percent or less PMN's and 88 percent had glucose and protein concentrations within the range of normal limits. All patients had a Gram-stained smear of CSF that revealed no organisms. In no instance was a CSF culture positive for a bacterial pathogen. In most instances, cerebrospinal fluid that contains total white cell count and glucose/protein concentrations within limits of normal, Gram-stained smear which reveals no organisms, and a differential cell count with less than 20 percent PMN's is not indicative of risk for bacterial meningitis. If the clinical situation warrants, the majority of children with this profile do not require hospitalization and initiation of empiric antibiotic therapy pending CSF culture results. PMID- 3349727 TI - The accuracy of blood glucose testing by children. AB - While studies have evaluated the accuracy of adult patients and health personnel in reading various glucose oxidase impregnated strips to estimate blood glucose, there are no studies exclusively evaluating the accuracy of children with diabetes reading their own strips as compared to a staff member, and meter to meter variability in reading these strips. We evaluated the accuracy of reading chemstrip bG by children at a summer camp. The children's visual readings of their own strips were compared to the visual reading of a single staff member. A total of 356 Chemstrip bG's were visually read by diabetic children and a single trained staff member at a summer camp for diabetics. The strips were then analyzed by two Accu-Chek bG meters. Intermachine variability was found to be negligible over the entire bG range. For the purposes of this study, we define accurate visual readings as those within +/- 15 percent of the meter reading of a given strip. At low bG values (40-79 mg/dl), accuracy by children and staff is low, with underestimating occurring in 39 percent of staff readings and 57 percent of children's readings. At intermediate bG values (120-239 mg/dl) readings are more accurate, especially when read by the staff, with misreadings occurring in only 16-19 percent of the strips. At high bG values (240-399 mg/dl), accuracy by children is decreased, with underestimation 500 percent more often than staff. We conclude that children are less accurate at reading Chemstrip bG than a trained staff member (51% versus 33% misreading), especially at the upper and lower ranges of bG values when visual readings are least accurate, and the need for therapeutic intervention is the greatest. PMID- 3349730 TI - Multidisciplinary team evaluation of school dysfunction. An analysis of utilization. AB - Little is known of the characteristics of children experiencing school dysfunction who are evaluated by multidisciplinary teams. The records of 87 children seen during a calendar year were reviewed and information was gathered regarding their age, sex, and referral source. In addition, the chief concerns of the child's parents and educators, and the diagnostic outcome, were considered. Boys were more likely to have been referred for behavioral problems than for academic issues. Girls were seen at an earlier age. Younger children were more likely to have been referred by physicians. While there was a significant association between gender and reason for referral, we found no such relationship between gender and final diagnostic classification. Variables in the utilization of evaluation services are described. Cognizance of these issues should lead to improved provision of care to all children experiencing school dysfunction. PMID- 3349731 TI - Hydrops fetalis due to ABO incompatibility. AB - Hemolytic disease of the newborn due to ABO incompatibility was first observed by Halbrecht in 1944. This entity has a spectrum ranging from minimal hemolysis requiring no therapy, as is the case in most instances, to severe hemolytic disease requiring aggressive management including exchange transfusion in a small percentage of cases. An extreme degree of hemolytic disease of the newborn due to ABO incompatibility, i.e., hydrops fetalis, has not been well documented in the English literature. We present a case of hydrops fetalis due to ABO incompatibility. The severity of hemolytic disease due to ABO incompatibility can be forecast when indicated in selected cases. PMID- 3349732 TI - Vulvar hemangioma simulating child abuse. AB - An infant with a vulvar hemangioma that had undergone extensive ulcerative changes was initially diagnosed as having a perineal burn secondary to child abuse. Although genital burns are a well-recognized manifestation of child abuse, knowledge of the natural course of untreated hemangiomas and the uncommon complication of ulceration as well as familiarity with the characteristic patterns of abusive burn injuries may allow the physician to avoid making this misdiagnosis. The confusion in diagnosis led to an extensive social service investigation that, in this case, had a positive outcome for the mother's ability to cope. There exists, however, the possibility of iatrogenic-induced emotional stress if child abuse is misdiagnosed. PMID- 3349733 TI - Oculoplastic surgery. PMID- 3349734 TI - Cosmetic and functional considerations in ptosis surgery. The elusive "perfect" result. AB - Correction of ptosis to achieve a fair or even good result is usually possible, but the "perfect" result is often elusive. Many factors play a part in diagnosis and repair of the ptotic lid, and these factors may enhance or inhibit the achievement of the best result. The correct operation must be selected for each type of ptosis with the realization that the best obtainable result may necessarily fall short of the elusive "perfect" result. PMID- 3349735 TI - Nasolacrimal disorders and their treatment. AB - Dysfunction of the excretory part of the nasolacrimal system may be congenital in otherwise normal infants or associated with congenital facial anomalies. It may also occur as a result of soft-tissue trauma to the face and naso-orbital fractures. Dacryocystorhinostomy and conjunctivodacryocystorhinostomy are discussed as treatment techniques. PMID- 3349736 TI - Nasoethmoidal and orbital fractures. AB - It is helpful to consider fractures of the orbit both in terms of their location and fracture pattern. CT scanning is an invaluable aid to the diagnosis and treatment of all orbital fractures. Early operative intervention, wide exposure, and accurate and stable fixation accompanied by immediate bone grafting provide the most successful treatment of fractures of the orbit. PMID- 3349737 TI - Reconstruction of the medial canthus. AB - The keystone for successful reconstruction of the medial canthal area is adequate positioning of the medial canthal complex to maintain proper intercanthal distance and apposition of the lids to the globe. This requires an understanding of the dynamics of the tripartite insertion of the MCT and its relationship to the medial orbital wall. We have previously described a technique for transnasal wiring based on anatomic studies that is anatomically and physiologically precise and that is applicable to a variety of clinical situations. Soft-tissue problems need to be dealt with on an individual basis with grafts, flaps, or a combination of these modalities. PMID- 3349738 TI - A multidisciplinary approach to orbital neoplasm. AB - The patient with orbital and periorbital neoplasia requires careful assessment of the extent and biologic activity as well as histopathologic categorization. Treatment is optimal through a multidisciplinary approach involving the ophthalmic surgeon, plastic surgeon, neurosurgeon, head and neck surgeon, and oral surgeon. PMID- 3349739 TI - Surgical approaches to orbital tumors. AB - Three approaches as used with modern technology, magnification with an operating microscope, and self-retained retraction have been presented. These approaches have allowed satisfactory exposure of difficult retrobulbar orbital areas from the various directions and have allowed us to more comfortably microdissect and remove orbital tumors. They also provide good exposure for the use of the carbon dioxide laser, which has been an aid in removing the intraorbital extensions of meningiomas, plexiform neurofibromas, and difficult lymphangiomas that occupy the intraconal compartments of the orbit. These approaches should only be undertaken by a skilled ophthalmic orbital surgical team in the case of the anterior medial and lateral approach, and definitely by a well-experienced neurosurgical/ophthalmic orbital team for tumors involving the orbital cranial junction and the superior orbital compartment. Experience gained over 17 years has convinced us that a team approach is mandatory for the difficult deep intraorbital tumors, even with the anterior medial or lateral approach. PMID- 3349740 TI - Selective microvascular procedures in oculoplastic surgery. AB - The aesthetic and functional reconstruction of the orbital and periorbital anatomy poses a complex challenge to the reconstructive surgeon. Four clinical cases are illustrated regarding the restoration of contour, and coverage of vital structures following tumor resections. PMID- 3349741 TI - Cosmetic upper blepharoplasty. AB - The anatomy of the upper eyelid is complex; however, those structures that make it complex are not involved in routine cosmetic blepharoplasty. The most common reason for patients seeking cosmetic surgery of the upper eyelids is excess skin and its associated heaviness. Appropriate removal of skin, preseptal orbicularis oculi muscle, submuscular fat, and orbital fat will achieve consistently good results. PMID- 3349742 TI - Lower lid blepharoplasty with skin flap and muscle split. AB - A skin flap, muscle split lower eyelidplasty is recommended for the management of excess skin of the lower eyelids associated with herniated infraorbital fat pads. Precise fat pad removal and skin excision are necessary. PMID- 3349743 TI - Skin-muscle flap lower lid blepharoplasty. AB - Lateral to medial dissection in the "potential space" between the orbicularis oculi muscle and the septum orbitale simplifies the skin-muscle flap lower lid blepharoplasty. The procedure is safe, rapid, and atraumatic. PMID- 3349745 TI - The right to health care? PMID- 3349744 TI - Complications of blepharoplasty. AB - Various involutional eyelid changes, such as fine rhytids, dynamic laugh lines in the lateral canthal area, secondary malar bags, and dermal pigmentation are not effectively treated by a blepharoplasty. Preoperative discussions are important to ensure that adequate expectations are held. Too often, a patient is informed that fine rhytids and dermal pigmentation can be successfully treated with lid surgery alone. The importance of the preoperative interview in determining patient expectations cannot be minimized. Preoperative ophthalmic and periocular examination is essential to identify any pre-existing pathology. Even though the surgical approach is adapted to the individual needs of each patient, the most meticulous of surgeons is predetermined to encounter his or her share of complications. There is a fine line between a "complication" and a common, but unwanted, sequela of surgery. Patients, overwhelmingly, do have some widening of their palpebral fissures, even following conservative surgery. Unfortunately, this occasionally creates ocular irritation or gross discomfort in allergic or borderline dry eyed patients. Lower eyelid bowing is so common even in the face of minimal skin resection that we do not consider it a "complication" if it does not produce a functional problem. It is humbling for all surgeons to review their blepharoplasty problems and helpful to recognize that, statistically, we are all due to face these events eventually. PMID- 3349747 TI - Patient's access to medical records. PMID- 3349746 TI - Colorado obstetrical care malpractice study report. PMID- 3349748 TI - Comparative bioavailability of two oral sustained-release procainamide products. AB - The bioavailability characteristics of two sustained-release oral procainamide preparations, Procan SR and Pronestyl-SR, were compared in 10 patients with arrhythmias. Each patient was randomly assigned to receive either Procan SR 1 g or Pronestyl-SR 1 g, both administered orally every six hours. The initial drug was continued for 48 hours (eight doses), at which time the second drug, given at the same dosage and dosing interval, was substituted for a 48-hour period. Serum samples for procainamide determination were obtained hourly between 42 and 48 and between 90 and 96 hours after initiation of procainamide therapy. Values for area under the serum concentration-time curve (AUC) during the steady-state dosing interval, maximum serum drug concentration (Cmax), minimum serum drug concentration (Cmin), Cmax:Cmin ratio (representing fluctuations in serum drug concentrations within the dosing interval), and the time to maximum serum drug concentration (tmax) were determined. Mean ( +/- S.D.) tmax values for Procan SR and Pronestyl-SR were 2.2 +/- 0.8 hours and 3.8 +/- 1.1 hours, respectively. Only the differences between tmax values were statistically significant. The study had an 83% chance of detecting a 20% difference in AUC values. The chances of detecting a 20% difference in values for Cmax and Cmin were 62% and 71%, respectively. These two preparations would probably possess similar therapeutic properties when given at the same dosage and dosing schedule; however, studies with larger subject populations are needed to project bioavailability data to the general population. PMID- 3349749 TI - Effect of diphenoxylate with atropine sulfate on the bioavailability of quinidine sulfate in healthy subjects. PMID- 3349751 TI - Comparison of 16-meq and 20-meq daily potassium supplement regimens. PMID- 3349750 TI - Association between depression and propranolol use in ambulatory patients. PMID- 3349752 TI - Phenytoin-induced pseudolymphoma with mycosis fungoides manifestations. PMID- 3349754 TI - Effects of propranolol and verapamil on plasma ionized calcium and parathyroid hormone in short-term intense isokinetic leg exercise. AB - Physical exercise, beta-adrenergic stimulation and calcium channel blockade can affect calcium homeostasis. The present study investigated, in eight healthy males, the effects of orally administered propranolol or verapamil during a 2-min maximal, isokinetic, leg exercise. Immediately after exercise the plasma ionized calcium concentrations were increased, in control and drug tests, by 5-6%, and within 5 min of recovery they were almost returned to baseline. Serum parathyroid hormone (PTH) concentrations were unchanged at termination of exercise, but they increased during the first 5 min of recovery, coincident with the decline in calcium concentrations, which, however, were still elevated. Neither verapamil nor propranolol selectively changed basal or exercise plasma ionized calcium or serum PTH concentrations. Muscle strength, blood pH, lactate concentrations and plasma volume changes were not affected by any drug. Verapamil did not have any specific effect on the concentrations of plasma magnesium, phosphate, potassium or sodium while propranolol increased the concentrations of plasma potassium and decreased those of phosphate during exercise as well as recovery. PMID- 3349753 TI - Anabolic steroid use as an AIDS risk factor. PMID- 3349755 TI - Angiotensin II attenuates reflex decrease in heart rate and sympathetic activity in man. AB - Circulatory variables and hormone concentrations in arterial plasma were measured in six normal subjects during angiotensin II (ANG II) step-up infusion of 0.25 and 1.00 ng kg-1 X min. During the 1.00 ng kg-1 X min infusion ANG II plasma concentrations increased from 11 +/- 2 to 48 +/- 6 pg ml-1; i.e., similar to those obtained during acute hypotensive hypovolaemia in man. Mean arterial pressure increased (P less than 0.05) from a resting value of 89 +/- 3 to 97 +/- 5 mmHg. Heart rate and catecholamine concentrations did not change. Plasma aldosterone increased (P less than 0.05) from 36 +/- 4 to 77 +/- 10 pg ml-1 during the infusion. Plasma concentrations of vasopressin, adrenalin and pancreatic polypeptide did not change during the investigation. During the 0.25 and 1.00 ng kg-1 X min infusion subcutaneous blood flow decreased (P = 0.06) to 67 +/- 20 and 66 +/- 26%, respectively, of control. It is concluded that: (1) ANG II in physiological doses in man may augment the sympathetic activity on the circulatory system since compensatory decreases in heart rate or in plasma catecholamines were not observed during the increased arterial pressure; (2) ANG II does not induce a general decrease in vagal tone as plasma pancreatic polypeptide concentrations were unchanged; (3) the obtained plasma concentrations of ANG II do not stimulate the release of vasopressin to plasma; and (4) the threshold for reducing the subcutaneous blood flow is reached within relatively small increments in plasma ANG II. PMID- 3349756 TI - Measurement of global and regional left ventricular performance with isotope technique in coronary heart disease. AB - In order to evaluate the left ventricular function in coronary artery disease, radionuclide measurements of global and regional ejection fraction (EF), regional wall motion and phase analyses of the left ventricular contraction were performed by equilibrium technique. One group of patients with angina pectoris and one group with myocardial infarction were compared with a control group. All the above-mentioned parameters significantly separated the infarction group from the reference group both at rest and during work, while the group of patients with angina pectoris showed disturbances mainly during work, such as impaired ability to increase global and regional ejection fraction and regional wall motion. Adding regional analysis and phase analysis to the global EF determination increases the possibility of studying the left ventricular function. However, this addition has a limited value in detecting impaired left ventricular function compared to the determination of just global EF in patients with angina pectoris and in patients with myocardial infarction. PMID- 3349758 TI - 7th Scandinavian Congress of Clinical Physiology. 28-29 August 1987, Copenhagen, Denmark. Abstracts. PMID- 3349757 TI - Left ventricular volumes during graded upright exercise in healthy untrained subjects. AB - Left ventricular (LV) volume changes were studied by radionuclide cardiography at rest and during graded upright bicycle exercise in seven healthy untrained men aged 21-30 years. The exercise-induced changes in LV volumes were most pronounced during mild exercise: from rest to 25% submaximal exercise stroke volume increased by 26% and LV ejection fraction from 0.60 to 0.69 (both P less than 0.01), whereas further increments of the work load resulted in only small changes of these variables. LV end-diastolic volume increased initially by 10% (P less than 0.05) but returned to baseline values at higher work loads, whilst a rather constant decrease was recorded in LV end-systolic volume during increasing exercise loads. Changes in plasma catecholamine levels were most pronounced at the high work loads, indicating that these hormones are not directly contributing to the LV volume changes. PMID- 3349759 TI - The low physical working capacity of thyrotoxic patients is not normalized by oral antithyroid treatment. AB - The low working capacity in thyrotoxic patients has not been quantified and its causes have not been clarified. We studied the working capacity in nine thyrotoxic patients at diagnosis (test 1), after 3 months of oral antithyroid medication (test 2), and in four of them again after 1 year (test 3). The maximum power output was low in thyrotoxic patients (1.65 +/- 0.15 W/kg-1) and was not significantly higher after 3 months of treatment (1.84 +/- 0.15), although plasma thyroid hormone concentrations had been normalized for approximately 3 months. After 1 year's treatment the maximum power output was still somewhat low in the four tested patients (2.75 +/- 0.34). The rate of oxygen uptake under maximum exercise was low (26 ml/min-1/kg-1) and was not significantly increased at test 2 and 3. The net mechanical efficiency was low at test 1 and 2 (18.9 +/- 2.1% and 20.1 +/- 1.8%, respectively), but was normal at test 3 (25.2%). At all three tests the blood lactate response upon maximum exercise attained only about 50% of normal concentration. Thus, low work capacity in thyrotoxic patients remained for a long period of time after euthyroid conditions had been attained. The low capacity was due to low aerobic and anaerobic capacities and initially also to a low mechanical efficiency. PMID- 3349760 TI - Mechanical ventilation. PMID- 3349761 TI - The relation between linguistic structure and associative theories of language learning--a constructive critique of some connectionist learning models. PMID- 3349762 TI - Electrocardiomultigraphimeter using a home computer. AB - The drop in hardware costs has fostered the widespread use of home-computer systems. Because of this situation, the home computer can be profitably employed in some highly specialized fields. We believe electrocardiographic instrumentation to be one such field. We have built an electrocardiomultigraphimeter (ECXGM), which can be considered as a development of the traditional electrocardiograph that performs some additional functions. Our prototype features vectorcardiography, polar coordinate tracing, automatic measurements between fiducial points selected by the user with a joystick and screen cursor and trace filing by patient on labelled floppy disks. The standard hardware consists of a Commodore 64 console, a monitor, two floppy disk drives and an Epson HI-80 plotter, all of which are readily available. The special hardware consists of an A/D converter, which receives the electrocardiographic signal downstream of the amplifying stage, which is a standard feature of any electrocardiograph. Prototype development mostly involved the software. Difficulties were posed by the limited resources available on home computers, an important point in view of the problem to be tackled. The solutions adopted are based on the use of assembler language and overloading techniques and minimizing the interconnections among the software modules defined in a compactly built program. The result is an instrument with significantly advanced clinico scientific capabilities as compared to current electrocardiographic instruments. This fact, and the class of the hardware used and special software built, confer originality to this work. The new instrument ought to be especially suitable for the offices of cardiologists who have an interest in such capabilities, and for schools of electrocardiography. PMID- 3349764 TI - SMR (simulating medical reasoning): an expert shell for non-AI experts. AB - SMR is an expert system shell designed to put the tools for knowledge acquisition directly into the hands of the domain expert. Since the knowledge base is represented as free text within a simplified syntactic structure, it is intelligible to anyone familiar with medical terminology. The knowledge base includes the rules for inference making as well as data groupings and protocols to facilitate case recording. In this paper, SMR is presented from the expert's point of view, describing the rule syntax and procedures for formulating the required diagnostic or therapeutic knowledge in the chosen domain. Similarly, the end-user's application of the system to patient data and the provisions for exploring and explaining the system's conclusions and reasoning processes are detailed. Avoiding tedious and often inane dialog, the user enters all that is known about the patient and receives a report of the system's conclusions and recommendations followed by a list of observations to be made in patient follow up. An expert system for evaluating the diabetic patient is used to illustrate system operations. PMID- 3349763 TI - Simulation of sensory neuronal discharge characteristics: the effects of multiple receptor sites and sources of variability. AB - There is conflict in the literature concerning the effect of multiple receptive endings on sensory afferent discharge. We simulated the discharge of intrapulmonary chemoreceptors of ducks and studied the effect of numbers of receptive endings, membrane 'noise' and changes in receptor threshold and gain. We found increasing membrane noise could not account for variability in spontaneously discharging intrapulmonary chemoreceptors and that, over a wide range of amplitude of various sources of noise, increasing the number of receptive endings increased discharge frequency and precision of transduction of the stimulus by reducing variability. PMID- 3349765 TI - Three-dimensional echocardiographic reconstruction: qualitative and quantitative evaluation of ventricular function. AB - Three-dimensional (3-D) images of the human left ventricle were reconstructed from 2-dimensional echocardiographic pictures. All images were recorded at held end-expiration from an optimal point where a high-quality parasternal long-axis view maximally visualizing the left ventricle could be obtained. Multiple short axis views were obtained from the same reference point. Interactive computer techniques were used to reconstruct 3-D shells of endocardium and epicardium. End diastolic and end-systolic outlines were superimposed after correcting for motion during the cardiac cycle to demonstrate wall motion. Images were displayed from different perspectives and regional wall thickness, thickening, and motion were then demonstrated using surface map displays. Volumes and derived indices of left ventricular function were calculated. The ejection fraction of normal patients was 69 +/- 9%, compared to 57 +/- 7% in infarct patients; the latter results correlated well with contrast angiography. 3-D echocardiographic reconstruction provides the observer with a spatial appreciation of left ventricular wall motion and thickness, as well as useful quantitative information. The system requires only a standard echocardiographic recorder and simple computer hardware. PMID- 3349766 TI - Implementation of multiuser MUMPS language database systems on microcomputers. AB - This paper outlines the problems involved in implementing multiuser MUMPS language database systems on microcomputers and discusses practical solutions. Examples of the techniques presented are derived from experience with a large database system, PTIN/PTQ/MEDAR, running on an IBM AT with up to 10 separate users. PMID- 3349767 TI - A syntactic method for analysis of nystagmus and smooth pursuit eye movement. AB - Eye movements are studied in neurophysiology, neurology, ophthalmology, and otology both clinically and in research. In this article, a syntactic method for recognition of horizontal nystagmus and smooth pursuit eye movements is presented. Eye movement signals, which are recorded, for example, electro oculographically, are transformed into symbol strings of context free grammars. These symbol strings are fed to an LR(k) parser, which detects eye movements as sentences of the formal languages produced by these LR(k) grammars. Since LR(k) grammars have been used, the time required by the whole recognition method is directly proportional to the number of symbols in an input string. PMID- 3349768 TI - Microcomputer-based system to measure, record and process flow-volume curves, respiratory questionnaire data and environmental exposure. AB - A microcomputer-based system was developed to measure flow-volume curve parameters, record respiratory questionnaire data and analyse the collected data. The hardware of the system consists of two parts which operate independently and are linked together for data transfer. The first part is a microprocessor-based unit to accurately measure flow-volume curve parameters. The second part is a microcomputer unit used to receive flow-volume curve parameters from the first part, to record responses to questionnaires stored in the unit and to perform all statistical analysis. The software included a monitor program controlling system operations, a data base and a powerful statistical package. Two sets of questionnaires are stored in the system, one for adults and the other for children. The user is only required to enter to the system answers to questions displayed on the screen. Flow-volume data can be entered via the keyboard of the microcomputer unit or transmitted from the flow-volume test unit. The developed system is compact, easy to operate and moderately priced. PMID- 3349769 TI - Facilities for digital pattern recognition: an ECG detective trick. AB - Algorithms for digital pattern recognition optimized for the demands of the physician are urgently needed. They have to provide high levels of recognition, accuracy, reliability, artefact rejection and flexibility in detecting different types of signal time-course. The microcomputer algorithm presented here works on the principle of Walsh-transformation of signal sections and in-image judging. The algorithm efficiently solves simple tasks, and also recognizes, for instance, ECG P-waves using the same algorithm. A test with 1054 randomly selected outpatient's ECG and with an additional 72 ECGs of inpatients with clinically proved myocardial infarcts produced the following results: The recognition ratio for the R-wave amounted to 98.8% with a failure ratio of 2.3%, while an initial common P-T-pattern was correctly recognized in 80.3% of cases, with a failure ratio of 4.9%. The algorithm was implemented on a Z80 microprocessor and on a single-chip computer Z8. PMID- 3349770 TI - An iterative phase correction program for nuclear magnetic resonance (NMR) spectra. AB - An iterative algorithm is given to correct for the zeroth and first order phase errors in NMR spectroscopy. A FORTRAN computer program is listed and two sample runs exemplified. No a priori knowledge of the existing phase errors is required. The parameters are optimised iteratively under the assumption that when the spectrum is correctly phased the ratio of the area above the spectrum to that below it is a maximum. PMID- 3349771 TI - Top-down design of a picture archiving and communications system (PACS) by means of simulation. AB - The development of picture archiving and communications systems (PACS) for medical applications can be regarded as a challenging field in medical informatics. Since 1982, several projects have been started into this direction worldwide. The Dutch IMAGIS (Image Information System) project, started in 1984, is one of them. Within this project, a top-down design strategy is chosen, with the following first steps: (1) A thorough information analysis for a Radiology Department, in which both qualitative and quantitative aspects are included. Such an analysis can be used to estimate the workload on a future PACS system. (2) The construction of a flexible performance prediction tool, based on discrete even simulation. Such a tool can be used to predict the performance of a certain computer system configuration under a certain workload. Based on the information analysis, and using the performance prediction tool, a PACS system is drafted for the thorax section of the Diagnostic Radiology Department of the Leiden University Hospital. In this first design attempt, the assumption was made that current working procedures concerning images will be maintained as much as possible. PMID- 3349772 TI - BASIC programs to analyse minimal inhibitory concentration (MIC) antimicrobial susceptibility results. AB - BASIC programs have been written to analyse minimal inhibitory concentration (MIC) antimicrobial susceptibility results for large numbers of organisms and a wide variety of antimicrobials. The output of the programs lists the numbers, percentages, cumulative numbers and cumulative percentages of organisms inhibited at different concentrations. The distribution of MICs are additionally printed as a histogram. The range, MIC for 50% and 90% of organisms (MIC50 and MIC90 respectively), and the geometric mean MIC of each drug are also calculated. PMID- 3349773 TI - Sensitization to patch test acrylates. AB - Data on allergic contact dermatitis from acrylates and 4 patients sensitized during routine patch testing are reported. During 1982-1985, we used 7 different acrylates for tests. 1 patient out of 22 (= 4.5%) was sensitized to ethyl acrylate and butyl acrylate (1% pet.). Since September 1985, we have used a commercial (meth)acrylate series containing 28 substances. 3 of 24 patients tested became sensitized to ethyl acrylate, 2-hydroxyethyl acrylate and 2 hydroxypropyl acrylate (0.5% pet.). Because active sensitization with acrylates can be very harmful, it may be necessary to use lower concentrations than recommended. Currently, we test ethyl acrylate, 2-hydroxyethyl acrylate and 2 hydroxypropyl acrylate at 0.167% pet. PMID- 3349774 TI - Experimentally-induced irritant contact dermatitis. Determination of optimum irritant concentrations. AB - Patch testing with 7 irritants has been performed on a panel of 42 healthy volunteers, with the aim of determining concentrations which would induce mild to moderate reactions in at least 75% of individuals tested. The irritants studied and their optimum concentrations were as follows: benzalkonium chloride, 0.5%; sodium lauryl sulphate, 5%; croton oil, 0.8%; dithranol, 0.02%; nonanoic acid, 80%; propylene glycol, 100%; sodium hydroxide, 2%. Responder rates lower than 75% had to be accepted for benzalkonium chloride and sodium hydroxide in order to prevent overly severe reactions, whilst propylene glycol proved to have only marginal irritant properties. PMID- 3349775 TI - Experiences with Freund's complete adjuvant test (FCAT) when screening for contact allergens in colophony. AB - A procedure, using Freund's complete adjuvant test (FCAT), for the determination of the allergenic potential of fractions and components in colophony of the gum rosin type is described and discussed. Gum rosin was shown to be a potent sensitizer in 11 test series (153 animals). FCAT is compared with the guinea pig maximization test (GPMT). Gum rosin was a potent sensitizer according to this method as well. The FCAT method was found to be advantageous over the GPMT method in that it is technically simpler to use and a smaller amount of test substance is needed. However, closed challenge was preferred to the prescribed open challenge. The importance of statistical evaluation of the results obtained in predictive testing is stressed. PMID- 3349776 TI - Contact dermatitis in patients with leg ulcers. The prevalence of late positive reactions and evidence against systemic ampliative allergy. AB - 100 patients with leg ulcers were patch tested against a standard battery of allergens. The readings were carried out daily from the 2nd to the 7th days. 55 patients showed positive reactions to one or more allergens. 32% of positive reactions developed for the first time after 48 h and 11% after 72 h. No single day or combination of two days gave 100% positive results. A single reading on the 4th day gave the highest number of positive reactions at 92%. The prevalence of positive patch tests was significantly higher in patients with surrounding eczema, and in patients with positive patch tests the ulcer duration was significantly longer than in those with negative patch tests. The total number of positive results in individuals increased linearly with the duration of the ulcer. Of allergens to which the ulcer was exposed, the occurrence of multiple sensitivity was significantly greater than predicted from the prevalence of individual sensitivities. However, there was no association between medicaments and metal sensitivity. This, together with the absence of an exponential rise in the number of allergens with the duration of ulcer, does not support the theory of systemic ampliative allergy. PMID- 3349777 TI - Sensitization studies in the guinea pig with the active ingredients of Euxyl K 400. AB - The preservative Euxyl K 400 consists of the 2 active ingredients, 2 phenoxyethanol and 1,2-dibromo-2,4-dicyanobutane. Sensitization studies with the guinea pig maximization test were performed with these substances, but no sensitizing capacity was demonstrated in the case of either compound. PMID- 3349778 TI - Contact allergy to a cyclohexanone resin in humans and guinea pigs. AB - 5 patients with allergic contact dermatitis caused by various paints were demonstrated to be sensitive to a cyclohexanone resin (C-R) present in the paints. Sensitization studies in guinea pigs with C-R and cyclohexanone showed one batch of C-R to be a sensitizer. PMID- 3349779 TI - Nickel sensitivity from dental prosthesis. PMID- 3349780 TI - Allergic contact dermatitis from minoxidil. PMID- 3349782 TI - Risk of sensitisation to Kathon. PMID- 3349781 TI - Contact allergy to Nobecutan. PMID- 3349783 TI - Allergic contact dermatitis from henna. PMID- 3349784 TI - Chromate dermatitis from a homeopathic drug. PMID- 3349785 TI - Systemic contact dermatitis after inhalation of 2-aminothiophenol. PMID- 3349786 TI - Kathon CG in cosmetics. PMID- 3349787 TI - A cutaneous manifestation of trichloroethylene toxicity. PMID- 3349788 TI - The sensitizing capacity of tixocortol pivalate. PMID- 3349789 TI - Corneal modeling. AB - The Corneal Modeling System is presented as an integrated instrument system designed to give the corneal surgeon the capability of measuring and designing alterations of corneal shape that are comparable to the computer-aided design (CAD) capability used in aerospace design and other industries. The system provides realtime digital video image acquisition using a high-resolution, cylindrical photokeratoscope and scanning laser slit lamp. From these digitized images, the system's computer derives topographic and pachymetric information in sufficient density to produce a continuous mathematical function that represents both the front and the back surface of the cornea. The mathematical model may then be sampled in as many points as the clinical application requires, in the form of either computer graphics or a numerical data stream to control precision machinery to make contact lenses or tissue lenses. Representative computer graphics of normal and pathologic corneal conditions are presented. PMID- 3349790 TI - Elevated tear IgG and conjunctival plasma cell infiltrate in a graft versus host disease patient. AB - Two patients developed graft versus host disease (GvHD) following allogeneic bone marrow transplantation for leukemia. One patient developed acute GvHD 12 days after transplantation, and the second developed chronic GvHD 100 days after transplantation. Tear analysis and conjunctival impression cytology were performed. The results were compared to a normal control and to another patient who was 18 months status post bone marrow transplantation with successfully treated GvHD. Tear sampling on the patient with chronic GvHD revealed greatly elevated IgG levels with an inverse IgG to IgA ratio, as compared with normals. In addition, two of three leukemia patients demonstrated decreased mucin levels in tears. Conjunctival impression cytology from the patient with chronic GvHD revealed an abundance of plasma cells. PMID- 3349791 TI - Variability in aminoglycoside pharmacokinetics in critically ill surgical patients. AB - The pharmacokinetics of the aminoglycosides were evaluated in 181 patients admitted to a surgical ICU. Pharmacokinetic parameters changed from 16% to 40% during therapy requiring multiple dosage adjustments and nearly nine drug levels per patient. Dosage adjustments resulted in peak and trough serum concentrations within the therapeutic range 71% and 74% of the time. Aminoglycoside half-life (T1/2) ranged from 1.1 to 69.3 h. Aminoglycoside volume of distribution also varied considerably with an average value of 0.36 L/kg. During therapy most patients gained weight (average 8.4 kg) which correlated with their corresponding fluid gain of 11.6 L. Pharmacokinetic parameters were variable even in patients with a normal serum creatinine. Less than 50% of these patients received the recommended daily dosages. This study suggests that the aminoglycoside volume of distribution in critically ill surgical patients differs from general hospital patients and pharmacokinetic parameters change considerably during therapy. We recommend obtaining timed serum aminoglycoside concentrations early in therapy and adjusting drug dosages as needed to maintain serum concentrations in the therapeutic range. PMID- 3349792 TI - Society of Critical Care Medicine, seventeenth annual educational and scientific symposium. Orlando, Florida, May 31-June 3, 1988. Abstracts. PMID- 3349793 TI - Syringomyelia: myelography, computed tomography, and magnetic resonance imaging. AB - Seventeen patients with cervical spinal cord cavities were studied with myelography, postmyelographic computed tomography scanning, and magnetic resonance imaging. The three diagnostic techniques were compared for accuracy, patient comfort, and ease of procedure. Magnetic resonance imaging was the best diagnostic and most comfortable procedure. There is no need for myelography or postmyelographic computed tomography scanning for the evaluation of cervical syringomyelia. PMID- 3349794 TI - High resolution computed tomography of the cadaveric sternoclavicular joint: findings in degenerative joint disease. AB - High resolution, narrow collimation, axial computed tomography of the sternoclavicular joint was used to describe changes secondary to degenerative joint disease in 32 cadaveric specimens. The distribution and pattern of sclerosis, cystic changes, and osteophyte formation in the axial plane were well demonstrated using this technique. Joint space narrowing was sometimes difficult to assess. Subtle joint space calcification was exquisitely demonstrated using computed tomography. Clavicular head cupping, an anatomic variant, may predispose to more severe degenerative change. Computed tomography is an excellent means to analyze the sternoclavicular joint for the presence of degenerative joint disease and may be the imaging modality of choice in assessing articular disorders of the sternoclavicular joint. PMID- 3349795 TI - The role of computed tomography in evaluation of skeletal metastases. AB - Computed tomography was performed in 100 patients for additional evaluation of suspected skeletal metastases following radionuclide bone scanning in 86 patients and conventional radiography in all. A retrospective review of these cases revealed that the majority (78%) involved the spine and pelvis. Computed tomography contributed to the diagnosis of a malignancy by revealing a definite destructive lesion of bone in 27 patients who had an abnormal radionuclide bone scan, a normal or inconclusive radiograph, or both. It excluded a malignant lesion in 19 patients. In 38 patients, computed tomography provided additional information that contributed to such aspects of patient care as obtaining tissue diagnosis, determining the extent of lesions, and evaluating the response to treatment. False diagnoses were made in two patients. Detection by computed tomography of a skeletal lesion and histologic documentation, frequently by computed tomography-guided percutaneous needle aspiration biopsy, greatly curtailed an otherwise extensive search for the primary site. Furthermore, this information altered the treatment plan by obviating the need for radical resection or biopsy of the primary tumor and by directing the choice of an appropriate chemotherapeutic regimen. PMID- 3349796 TI - Aggressive angiomyxoma with gastrointestinal communication: a case report. AB - We report the imaging findings of an abdominal aggressive angiomyxoma, which communicated with the gastrointestinal tract. The literature on this rare tumor is reviewed. PMID- 3349797 TI - Computed tomography examination of periampullary neoplasms. AB - The hospital records of 24 patients with periampullary neoplasms were reviewed. The clinical triad of jaundice, pain, and weight loss and the radiographic imaging triad of dilated biliary ducts, dilated pancreatic duct, and periampullary mass should suggest the diagnosis of periampullary neoplasm. PMID- 3349798 TI - Computed tomography of a traumatic, diaphragmatic, Richter's hernia: findings mimicking an abscess. AB - We present a case of a Richter's hernia through a traumatic, diaphragmatic defect presenting with the appearance of an abscess on computed tomography. We underscore the importance of this hernia variant, the need for its recognition, and stress caution in percutaneous aspiration of a lesion where a hernia might exist. PMID- 3349799 TI - Hyperdense pelvic and inguinal lymph nodes. AB - This small series reports on the computed tomography appearance of hyperdense iliac, inguinal, and femoral lymph nodes in four cases of lymphoma and one case each of ovarian and breast carcinoma. The mean attenuation value of the lymph nodes was 93.8 Hounsfield units (HU), compared to 61 HU for adjacent muscle and 110.7 HU for blood vessels. A relatively homogeneous enhancement pattern was noted, which could not be directly related to hypervascularity, inflammation, or previous treatment with drugs or radiation. PMID- 3349800 TI - Computed tomography of a symptomatic infarcted thoracic lipoma. AB - Intrathoracic lipomas are often asymptomatic and incidentally discovered on routine chest radiographs. An infarcted, pedunculated thoracic lipoma causing chest pain is described. The possibility of liposarcoma was suggested by an inhomogeneous computed tomography appearance and an attenuation value that was greater than that of normal subcutaneous fat. PMID- 3349801 TI - Solitary neurofibroma of the vagus nerve in the aortopulmonary window masquerading as a developmental cyst. AB - A rare case of solitary neurofibroma of the vagus nerve in the aortopulmonary window masquerading as a developmental cyst is reported. Its computed tomographic characteristics and magnetic resonance imaging are described and correlated with pathologic findings. Although the features of such imaging modalities are quite characteristic for a neurofibroma, its differentiation from "atypical" developmental cysts may be difficult. PMID- 3349802 TI - Focal cortical dysplasia on magnetic resonance imaging: a case report. AB - A case report of an 11 years old boy with new onset of a seizure disorder is presented. A computed tomography scan demonstrated a noncalcified, nonenhancing focal region of abnormal cortex. A magnetic resonance imaging scan delineated both an isointense area of abnormally thickened gyri and linear areas of abnormal high signal intensity in the subjacent white matter. A review of the radiologic and pathologic literature suggests that this lesion represents the entity focal cortical dysplasia as described by Taylor, et al. This abnormality is part of a spectrum of disorders including hamartomas (of tuberous sclerosis), focal cortical dysplasia and heterotopias. PMID- 3349803 TI - Unusual "cavity-in-cavity" appearance of pulmonary aspergilloma. AB - The classic radiographic appearance of pulmonary aspergilloma is a solid, round, often mobile intracavitary mass. We describe an unusual "cavity-in-cavity" appearance seen on conventional roentgenograms and computed tomography studies in two patients with confirmed pulmonary aspergilloma. We are not aware of any previous report describing such appearance based on literature search. PMID- 3349804 TI - Body computed tomography findings in systemic lupus erythematosus. AB - Fifty-five computed tomography scans in 27 patients with systemic lupus erythematosus were reviewed. The most frequent indication for scanning was suspected intraabdominal sepsis, and the most frequent finding was mild lymphadenopathy. Renal abnormalities were: subcapsular hematoma, focal defects, overall enlargement, and diminution of size. Other findings included serositis, bowel wall thickening with pneumatosis intestinalis, pancreatic pseudocyst, and hepatic and splenic enlargement. Five abscesses were found that were indistinguishable from other fluid collections. Computed tomography was helpful in clinical evaluation and in some cases changed management. PMID- 3349805 TI - Computed tomography and magnetic resonance imaging of a superior gluteal artery pseudoaneurysm. AB - The magnetic resonance and computed tomography appearances of a superior gluteal artery pseudoaneurysm are described, with emphasis on the relative advantages and disadvantages of these two imaging procedures. PMID- 3349806 TI - Magnetic resonance imaging in the diagnosis of a psoas abscess. AB - Identification of a psoas abscess is often a diagnostic challenge. In this case report the diagnosis and subsequent treatment of a psoas abscess previously suggested by computed tomography was greatly enhanced by magnetic resonance imaging. PMID- 3349807 TI - The bull's-eye sign of extracranial cervical aneurysms. AB - Extracranial, cervical aneurysms and arterial thrombosis are uncommon entities. In most cases, they have diagnostic clinical presentations. However, on occasion the history and physical findings do not clearly suggest their presence. In these cases, postcontrast computed tomography scans can aid in rapidly establishing the correct diagnosis by revealing a "bull's-eye" appearance within the mass (vessel lumen). The diagnosis is less difficult to make when the involved vessel is the carotid artery, because this artery is routinely identified on postcontrast computed tomography scans and the lesion can be easily placed along its course. The vascular origin of such a lesion is not usually evident on computed tomography if the process does not lie along the course of a major vessel. In these cases, the bull's-eye sign can establish the diagnosis so that prompt consideration can be given to angiography and therapy. PMID- 3349808 TI - Tension pneumocephalus five years after intracranial resection of pituitary adenoma--a case report. AB - A case of spontaneous pneumocephalus with progression to tension pneumocephalus is presented. It is unique because it occurred spontaneously via a sellar defect 5 years after resection and irradiation of a pituitary adenoma, without tumor recurrence. Computed tomography clarified the extent of the pneumocephalus and its progression to tension pneumocephalus. PMID- 3349809 TI - Functional testing of hepatocytes following their recovery from cryopreservation. AB - Various tests of function have been suggested for assessing hepatocytes recovered from cryopreservation. In this study we have investigated hepatocyte attachment during tissue culture and cellular density in order to assess function and compared them with two classical dye exposure tests. The ability of hepatocytes to exclude trypan blue dye (TB) and metabolize fluorescein diacetate (FDA) was demonstrated. In populations of freshly prepared hepatocytes 88.07% were able to exclude TB and 87.31% were able to metabolize FDA. However in populations of hepatocytes recovered after cryopreservation using 1.5 M dimethyl sulfoxide as cryoprotectant only 33.44% were able to exclude TB and 31.59% able to metabolize FDA. Both of these tests gave the same estimate of functional ability. Density gradient centrifugation of hepatocytes on Percoll 400 (Pharmacia, Uppsala, Sweden) separated two populations of hepatocytes; one (density ca.1.07 g/ml Percoll) in which most of the cells were able to exclude TB and the second (density ca. 1.02 g/ml Percoll) in which they were stained blue. The dense population was highly enriched in dye-excluding hepatocytes: freshly prepared hepatocytes, 92.4%, and cryopreserved hepatocytes, 88.66%. When samples of these cells (2 x 10(6) dye-excluding cells per dish) were tested for their ability to attach to tissue culture dishes only 17.28% of the cryopreserved hepatocytes were able to attach compared to 55.28% of the freshly prepared cells. We conclude that cryopreservation of hepatocytes produces a population of cells which are not metabolically identical to a population of freshly prepared hepatocytes even though they appear to have the same buoyant density and dye-excluding capabilities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349811 TI - Solute effects on ice recrystallization: an assessment technique. AB - Reliable assessment of the effect of a solute upon ice recrystallization is accomplished with "splat cooling," the impaction of a small solution droplet onto a very cold metal plate. The ice disc has extremely small crystals, and recrystallization can be followed without confusing effects caused by grain nucleation. This method confirms the exceptionally strong recrystallization inhibition effect of antifreeze protein from Antarctic fish and shows that grain growth rate is a sensitive function of both grain size and solute concentration. PMID- 3349810 TI - Cryoprotection of red blood cells by 1,3-butanediol and 2,3-butanediol. AB - 1,3-Butanediol and 2,3-butanediol have been used in buffered solutions with 20, 30, or 35% (w/w) alcohol to cool erythrocytes to -196 degrees C at different cooling rates between 1 to 3500 degrees C/min, followed by slow or rapid rewarming. 1,3-butanediol shows the same shapes of red blood cell survival curves as 1,2-propanediol. Having nearly the same physical properties, they have comparable effects on cell survival. The classical maximum of survival for intermediate cooling rates and an increase for the highest cooling rates are observed. This increase seems to be correlated with the glass-forming tendency of the solution. After the fastest cooling rates, a warming rate of 5000 degrees C/min is sufficient to avoid cell damage, but a warming rate of 100-200 degrees C/min is not. Yet both of these rates would be insufficient to avoid the intracellular ice crystallization on warming. The damage on warming after fast cooling seems once again to be correlated with the transition from cubic to hexagonal ice. For all our results, 1,3-butanediol is like a "second" 1,2 propanediol and could be useful as a cryoprotectant for preservation by total vitrification. 2,3-Butanediol always gives extremely low survival rates, though it presents good physical properties. The crystallization of its hydrate seems to be lethal on cooling or on rewarming. PMID- 3349812 TI - Velocity of linear crystallization of ice in macromolecular systems. AB - The velocity of ice crystallization in gelled systems was compared with that in solutions of similar macromolecular materials. Neither the constituting material nor the dimensions of the tubes in which the measurements were made influenced the results. The velocity of linear crystallization of ice was slowed in macromolecular solutions and gels, and this decrease was not associated with changes in dynamic or thermodynamic properties of water. It was probably the consequence of a mechanical effect of the macromolecules directly on ice crystal growth. PMID- 3349813 TI - Prediction of local cooling rates and cell survival during the freezing of a cylindrical specimen. AB - A finite element numerical model was implemented to simulate the freezing process of an aqueous salt solution in a cylindrical container. Local cooling rates within the container were computed for several defined cooling protocols applied at the boundary. Characteristic cell survival signatures were used to predict the associated local survival rates throughout the system. These calculations show that there are two definite time domains during a typical freezing process: (1) while the surface temperature is changing and (2) after the surface temperature reaches a constant storage value. The calculations also show significant spatial variations in the local cooling rates within the container and considerable local deviation from the volumetric average survival for various simulated freezing protocols. PMID- 3349814 TI - Platelet membrane in transfusion medicine. Second Canadian Workshop and Conference on Platelet Serology. Ottawa, January 9 and 10, 1987. Proceedings. PMID- 3349815 TI - Platelet utilization in cardiopulmonary bypass surgery. PMID- 3349816 TI - In utero fetal sampling in neonatal alloimmune thrombocytopenia: justification and usefulness. PMID- 3349817 TI - Screening for neonatal alloimmune thrombocytopenia: an economic perspective. PMID- 3349818 TI - Trends in platelet utilization in Canada 1981-1987. PMID- 3349819 TI - Platelet transfusion: utilization and control. PMID- 3349820 TI - Arm exercise and ventilation. PMID- 3349821 TI - Physician risk preferences and patient care. PMID- 3349822 TI - Conventional chest films can identify airflow obstruction. PMID- 3349823 TI - Aspiration resulting from gastroesophageal reflux. A cause of chronic bronchopulmonary disease. PMID- 3349825 TI - Upper extremity exercise training in chronic obstructive pulmonary disease. AB - Many patients with chronic obstructive pulmonary disease (COPD) report greater limitation for activities involving the upper extremities than the lower extremities. Exercise training has generally emphasized lower-extremity exercise. We designed and evaluated two simple, practical, and widely applicable upper extremity training programs in 45 patients with COPD participating concurrently in a comprehensive, multidisciplinary pulmonary rehabilitation program. Patients were randomly assigned to one of the following three groups: (1) gravity resistance (GR) upper-extremity training; (2) modified proprioceptive neuromuscular facilitation (PNF) upper-extremity training; or (3) no upper extremity training (control). Patients were evaluated before and after at least six weeks of uninterrupted training. Twenty-eight patients completed the study. Compared to controls, both GR and PNF patients demonstrated improved performance on tests specific to the training performed (upper-extremity performance test, maximal level and endurance on isokinetic arm cycle). There were no significant changes on isotonic arm cycle, ventilatory muscle endurance, or simulated activities of daily-living tests. Ratings of perceived breathlessness and fatigue decreased significantly in all groups for several tests. We conclude that specific upper-extremity training may be beneficial in the rehabilitation of patients with COPD and warrants further investigation. PMID- 3349824 TI - Risk preference and decision making in critical care situations. AB - Physician attitudes towards risk may influence their behavior in critical care situations. To explore this hypothesis, physicians' responses to a questionnaire about risk were compared to their preferences towards "intubation" or "current therapy without intubation" for a hypothetical patient with end-stage lung disease, and to the length of time they performed cardiopulmonary resuscitation before they declared their efforts unsuccessful. When the choices on the questionnaire were framed in terms of loss, choice of the risky alternative was associated with greater preference for "intubation," and with longer duration of resuscitation efforts (both p less than .005). At least part of the variation in physician attitudes and practices towards the care of the critically or terminally ill is associated with measurable psychologic differences among individual physicians. PMID- 3349827 TI - Portable chest roentgenography and computed tomography in critically ill patients. AB - Computed tomography (CT) of the chest offers improved resolution and sensitivity for evaluating chest pathologic conditions compared with other imaging techniques. Intensive care unit patients with portable chest findings that diverge from the clinical course may actually have severe intrathoracic disease that can be detected with CT. Our three patients demonstrate chest CT can aid in the diagnosis of significant intrathoracic pathologic conditions which have been significantly underestimated by portable chest roentgenography. We discuss the reasons for this improved detectability by CT, as well as suggest alternative techniques that can be performed at the bedside in patients whose initial portable chest roentgenogram and clinical course do not correlate. PMID- 3349826 TI - Failure of ambulatory electrocardiographic monitoring to predict results of programmed electrical stimulation. Studies in patients with clinical ventricular tachyarrhythmias. AB - To test for an association between the results of ambulatory electrocardiographic monitoring (AEM) and programmed electrical stimulation (PES), or whether other factors better predict the results of PES, 57 patients (36 male and 21 female patients) presenting with either ventricular fibrillation (49 percent; 28/57) or sustained ventricular tachycardia (51 percent; 29/57) were studied. Each patient underwent AEM and PES using up to three ventricular extrastimuli. Sixty-three percent (36/57) had coronary disease; and of these, ventricular tachycardia was present during AEM in 64 percent (23/36) and induced by PES in 78 percent (28/36). With the addition of patients with other cardiac diagnoses, the results were 58 percent (33/57) and 60 percent (34/57), respectively. No AEM variable was positively associated with inducible ventricular tachycardia, including frequency of ventricular premature depolarizations, multiformity, couplets, or ventricular tachycardia. Clinical variables positively associated with inducible ventricular tachycardia were coronary disease, previous myocardial infarction, left ventricular dysfunction, male sex, and a history of recurrent arrhythmia. Therefore, clinical characteristics are more useful for predicting the results of PES than information derived from AEM. PMID- 3349828 TI - An improved method of cell recovery following bronchial brushing. AB - Cytologic examination of bronchial brush specimens is effective in diagnosing bronchogenic carcinoma. A major problem is loss of cells and cellular detail associated with the direct smear technique (DST). A more recent method, the Saccomanno brush wash (SBW), uses a narrow-mouthed vial to scrape cells off the brush directly into fixative. We sampled 12 directly visualized airway tumors using standard brush technique. The same brush was then agitated in a SBW vial, which was centrifuged, the cell pellet being smeared over a predetermined area of a slide. Designated areas of each slide were counted and total malignant cells per slide extrapolated. DST slides had significantly fewer cells than SBW slides, and cellular detail was better with SBW in seven cases, DST in one case, and equal in four cases. SBW appears preferable for handling of bronchial brush specimens. PMID- 3349829 TI - Prediction of pneumothorax rate in percutaneous needle aspiration of the lung. AB - Pneumothorax (PTX) is the most common complication associated with percutaneous needle aspiration (PNA) of the lung. Age, sex, cooperation, and lesion size, location, and depth, as well as needle size, number of passes, and radiographic calculation of total lung capacity all have been implicated in influencing the rate of PTX. Pulmonary function testing to assess PTX risk in PNA has not been previously examined. We retrospectively reviewed 159 patients undergoing PNA who had preprocedure spirometry (PFT) and chest roentgenogram (CXR) interpreted for changes of obstruction or restriction to determine if these classifications could stratify patients at high risk for PTX. We also examined single variables to determine their predictive power. Patients with normal PFT and CXR had a 10 percent risk of PTX, and only one such patient needed intervention to treat the PTX. Obstruction by PFT, regardless of CXR findings, predicted a 50 percent PTX rate. Among single variables, FEV1 proved to be the most significant predictor of PTX. Preprocedure spirometric testing can enhance the assessment of PTX risk and should be routinely performed prior to needle aspiration. PMID- 3349830 TI - Bronchoscopic protected catheter brush for the diagnosis of pulmonary infections. AB - A new bronchoscopic-protected catheter brush (BPCB), designed to obtain uncontaminated bronchial secretions, was studied in vitro and in vivo. The device was composed of a standard biopsy brush, protected by a single catheter and occluded with an agar plug. Ejection of the plug was obtained neither by advancing the brush nor by advancing an inner cannula (as in a telescoping catheter brush), but instead, by an air flux, provided by a syringe which was connected to the proximal tip. In the first part of the study the ability of the BPCB to obtain uncontaminated specimens was tested in comparison with the reference telescoping catheter brush (BFW brush 10/70/90, Medi-Tech Corp Watertown, MA). Catheters of each type were successively passed through the inner channel of a bronchofiberscope which was contaminated with Klebsiella pneumonia. After ejection of the distal plug, sampling of bronchial secretions infected with a marker organism (Pseudomonas aeruginosa), was performed with the brush. Culture of brush specimens of each type of catheter grew the marker organism in pure culture and obtained the same amount of bronchial secretions (0.001 ml). The manual vortexing of the brush in the transport medium (Ringer's solution) proved to be as effective as the mechanical vortexing so that transecting of the brush was no longer mandatory. In the second part of this study, paired bronchial samplings from 27 patients were performed using both types of catheters and similar results for both were obtained. In these in vitro studies, completed by a clinical trial, our single-sheathed, plugged catheter brush proved to be as reliable as the double telescoping catheter brush. However, because of its relatively simple conception, making it easier to use and lower in cost than the double catheter brush, routine use of this sampling device should be considered. PMID- 3349831 TI - Variability of the breathing pattern before and after extubation. AB - A stable breathing pattern during unassisted ventilation through an endotracheal tube (ETT) prior to extubation is an important factor in determining whether a patient can be successfully extubated. Proper interpretation of changes in the breathing pattern requires knowledge of the normal variability of the breathing pattern in critically ill, intubated patients. To establish these guidelines, 50 spontaneously breathing patients who were being weaned from mechanical ventilation were monitored with respiratory inductive plethysmography for one hour immediately prior to and following successful extubation. Immediately after extubation, respiratory rate (f), tidal volume (VT), minute ventilation, and mean inspiratory flow increased slightly. By 30 minutes postextubation, these parameters were similar to preextubation values. There was no significant change in variability of f or VT. Although the breathing pattern of these relatively stable, intensive care patients differed from values of normal ambulatory subjects, values were similar in the preextubation and postextubation periods. PMID- 3349833 TI - Impaired exercise tolerance after inferior vena caval interruption. AB - Four patients were evaluated for persistent dyspnea eight months to four years after inferior vena caval interruption for treatment of pulmonary emboli. Maximal exercise testing with gas-exchange analysis was performed. All patients attained less than 64 percent of predicted maximal oxygen uptake. Peak exercise heart rates were 85 percent or greater of predicted values. Arterial hypoxemia was not observed. The ratio of dead space to tidal volume (VD/VT) decreased with exercise, and the ratios of maximal exercise ventilation to maximal voluntary ventilation (VE/MVV) were less than 67 percent. These results suggest a cardiac rather than a ventilatory limitation to exercise. Inadequate venous blood return to the heart is the likely mechanism for the impaired exercise performances. PMID- 3349832 TI - Tuberculosis and nontuberculous mycobacteriosis in patients with AIDS. AB - Thirty-six patients with AIDS and culture-proven nontuberculous mycobacteriosis were compared to 20 patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis with regard to clinical signs, symptoms, and diagnostic methods. Patients with nontuberculous mycobacteriosis were more often younger and homosexuals, while patients with tuberculosis were usually Haitian-American or users of intravenous drugs. A majority of patients with tuberculosis presented with fever and weight loss. These symptoms were seen in approximately 50 percent of the patients with nontuberculous mycobacteriosis. A distinct syndrome of dyspnea, chills, hemoptysis, and chest pain was seen in a significant minority of patients with nontuberculous mycobacteriosis. Lymphadenopathy was seen almost exclusively in patients with tuberculosis. Pulmonary sources (expectorated sputum or bronchoscopy specimens) were the most common source of diagnosis in both groups. Patients in both groups in whom the diagnosis was obtained from pulmonary sources frequently had negative chest x-ray films on presentation. Cavitary disease was absent from both groups. PMID- 3349834 TI - Ventilation with the esophageal tracheal combitube in cardiopulmonary resuscitation. Promptness and effectiveness. AB - The success of cardiopulmonary resuscitation after cardiac arrest depends not only on the duration of the arrest, but also on the prompt establishment of a patent airway. In this study, we tested the safety and promptness of intubation with esophageal tracheal combitube (ETC) when compared to conventional endotracheal airway. Effectiveness of ventilation via the ETC as shown by blood gas analyses appeared to be comparable to endotracheal airway. Data suggest that the ETC might serve as a useful device during cardiopulmonary resuscitation. PMID- 3349835 TI - The pharmacokinetics and efficacy of slow-release theophylline with asymmetric dosing in asthmatic Chinese. AB - Fifteen Chinese subjects with stable asthma were given asymmetric doses of slow release choline theophyllinate (Theobret) according to body weight; patients under 60 kg (132 lb) received 180 mg at 9 AM and 360 mg at 9 PM for six days (period 1), followed by 180 mg at 1 PM and 360 mg at 9 PM for six days (period 2); for those over 60 kg, the regimen was the same, except that they received 270 mg during the daytime and 540 mg at night. At the end of each period of treatment, concentration of theophylline was measured over 24 hours. Five patients experienced side effects, and two of these were withdrawn from the study. In the remaining 13 patients, optimal concentrations of the drug were attained during most of the 24 hours, and there were only minor pharmacokinetic differences between the two periods of treatment. Compared with observations before treatment, the total symptom score was unchanged, but the peak expiratory flow rate in the morning and evening improved, and the use of inhaled bronchodilator drugs decreased significantly. There was a trend towards progressive improvement as the duration of treatment increased, suggesting that the therapeutic effect of theophylline may lag behind the attainment of optimal concentrations. We conclude that asymmetric dosing regimens of slow-release theophylline are effective and rational in maintenance therapy for asthma and that lower total daily dosages may be more appropriate in Chinese patients when compared to those recommended for white subjects. PMID- 3349836 TI - Effects of fenoterol on oxygen transport in patients with chronic airflow obstruction. AB - A rise in cardiac output and a fall in arterial oxygen tension are well known side effects of bronchodilator drugs, particularly beta-adrenergic agonists. In recent years, fenoterol (Berotec), an effective beta-adrenergic agonist, has been used at increasing rates in asthmatic subjects, as well as in patients with chronic obstructive pulmonary disease (COPD). The effects of fenoterol on systemic hemodynamics or arterial oxygenation (or both) in patients with COPD have not been investigated; in these individuals, who often have increased sympathetic tone and hypoxemia even at rest, cardiovascular stimulation and a fall in arterial oxygen tension would be particularly undesirable side effects. In 14 patients with COPD (seven without a reversible component of airflow obstruction [group 1]; and seven with a reversible component of airflow obstruction [group 2]), we studied all of the important parameters of oxygen transport before and 60 minutes after administration of fenoterol. Studies were performed at rest and after exercise. At baseline, group 1 showed a faster heart rate, a lower cardiac output, a lower arterial oxygen flow, a wider arteriovenous oxygen content difference (C[a-v]O2), and a higher fraction of oxygen extracted by the tissues from a given arterial oxygen flow. In both groups, all measured parameters, including cardiac output and arterial oxygen pressure (PaO2) remained statistically unchanged one hour after administration of fenoterol; with exercise, the heart rate, blood pressure, minute ventilation, oxygen consumption, C(a-v)O2, and the percentage of oxygen extracted from arterial oxygen flow, as well as cardiac output and PaO2, increased in all instances; the exercise responses were not affected by the drug. These results suggest that at the time of its maximal effect on the airways (60 minutes), fenoterol has no untoward effect on the oxygen transport system, at rest or during exercise, in patients with COPD with or without a reversible component. PMID- 3349837 TI - Chest physiotherapy. Evaluation by transcutaneous blood gas monitoring. AB - Two respiratory physiotherapy methods were evaluated by analyzing changes in the transcutaneous partial pressure of CO2 (tcPCO2) in 15 patients with respiratory insufficiency. All were receiving continuous oxygen therapy and had CO2 retention. The physiotherapy methods compared were thoracic compression (TC) and positive expiratory pressure (PEP). The mean decrease (+/- SD) in tcPCO2 was the same with both methods, 0.6 +/- 0.4 kPa, but there were interindividual differences. This study indicates that both TC and PEP effectively decrease tcPCO2, although only temporarily in many cases. Continuous tcPCO2 monitoring is a useful clinical method for determining and teaching optimal respiratory therapy. PMID- 3349838 TI - Intentional isoniazid overdosage in young Southeast Asian refugee women. AB - During a two-year period, from January 1984 through December 1985, six cases of intentional overdosage with isoniazid were reported in young Southeast Asian refugee women. The patients were aged 14 to 23 years, had all immigrated within one year and were receiving isoniazid preventive therapy for tuberculosis infection without disease. Clinically, all patients experienced generalized seizures, and three sustained moderate metabolic acidosis. All recovered uneventfully. Psychiatric evaluations revealed that two patients had major depression; two, adjustment disorders with depressed mood; and two, no psychiatric illness. The latter two patients and two others ingested an excessive amount of isoniazid immediately following an argument with a family member. Because tuberculosis infection is prevalent in refugees immigrating from Southeast Asia, isoniazid, given for six months to one year as preventive therapy, is one of the most frequently prescribed drugs during the early resettlement period. There may be an increased risk of intentional isoniazid overdosage during preventive therapy of young refugee women. PMID- 3349839 TI - The prognostic significance of preoperative assessment of mediastinal lymph nodes in patients with lung cancer. AB - In order to evaluate the prognostic significance of the preoperative assessment of mediastinal lymph nodes, 100 patients with potentially operable lung cancer underwent two-plane tomography, computed tomography (CT), transbronchial needle aspiration (TBNA; 47 patients), and cervical mediastinoscopy. Mediastinoscopy proved to be the most accurate staging procedure. Tomography was less specific, detecting only advanced mediastinal node involvement, and CT was as sensitive as mediastinoscopy but sensibly less specific. TBNA gave no false positive results but a false negative rate of 25.5 percent. Accurate preoperative staging of mediastinal nodes is mandatory to optimize the resectability rate of lung cancer. Where metastatic involvement of mediastinal nodes was preoperatively documented at more than one level, tumors were invariably unresectable. Mediastinoscopic demonstration of intracapsular metastases at only one level did not preclude complete resection. Before thoracotomy, confirmation of neoplastic spread to mediastinal nodes suggests very low survival rates, especially in patients with incomplete removal of tumors. PMID- 3349840 TI - Increased intensity of the murmur of hypertrophic obstructive cardiomyopathy with carotid sinus pressure. AB - In a prospective study murmurs increased in intensity with carotid sinus pressure in 18 of 26 patients with hypertrophic obstructive cardiomyopathy (HOCM) (sensitivity, 69.2 percent for the 26 patients, 85.7 percent for the 21 patients in whom heart rate and blood pressure decreased with carotid sinus pressure). On the other hand, the murmur remained constant or decreased in all but one of 104 patients with valvular aortic stenosis, mitral insufficiency, hypertrophic nonobstructive cardiomyopathy, and systolic murmurs of miscellaneous origins (specificity, 99 percent; positive predictive value, 94.7 percent). Catheterization, indirect arterial pressure tracings, and echocardiographic studies indicated that carotid sinus pressure-induced bradycardia was associated with increased left ventricular outflow tract obstruction. The carotid sinus pressure-induced increase in the murmur is probably multifactorial: decreased aortic pressure and impedance; increased contractility immediately on sudden slowing of heart rate; further increase in obstruction as the mitral valve systolic anterior movement is enhanced; and delayed vasodilatation maintaining the obstruction even after return of heart rate to precarotid sinus pressure values. An increase in a systolic murmur with carotid sinus pressure is characteristic of HOCM. PMID- 3349841 TI - Comparison of antituberculosis drug regimens for lung disease caused by Mycobacterium avium complex. AB - A total of 123 patients with moderately advanced, cavitary lung disease caused by Mycobacterium avium complex untreated previously received different regimens of antituberculosis agents. The rate of sputum conversion (continuously negative cultures for six months or more) was compared among the regimens. It was shown that the regimens of rifampin + isoniazid + streptomycin and rifampin + isoniazid + enviomycin were superior to the regimens of streptomycin + isoniazid + p aminosalicylate, isoniazid alone or isoniazid + p-aminosalicylate. This finding demonstrated that the regimens including rifampin, isoniazid and streptomycin or enviomycin were really effective in the initial treatment of lung disease caused by M avium complex. PMID- 3349842 TI - Preclinical training in bronchoscopic diagnosis of cancer. AB - This study evaluated educational effectiveness of preclinical training of residents in diagnostic bronchoscopic techniques which used videotaped programs. Sixty-five residents in eleven medical centers were randomized. Experimental subjects viewed five videotaped programs dealing with bronchoscopic anatomy and pathology. Following their tenth clinical experience in bronchoscopic diagnosis, performance of both experimental and control subjects was objectively evaluated using a Visual Discrimination Test (VDT) that contained six videotaped sequences in suspected cancer patients. Clinical performance was subjectively evaluated by teachers who used a list of Minimum Competency Requirements (MCRs). Experimental subjects provided a significantly greater number of correct answers in the VDT and achieved higher scores for the MCRs that were specifically related to recognition of bronchoscopic anatomy and pathology. This study demonstrated that preclinical training using videotaped programs could improve visual perception and discrimination skills of residents in their bronchoscopic examination of patients with suspected cases of cancer. PMID- 3349843 TI - Endobronchial tuberculosis presenting as asthma. AB - Clinical deterioration with features suggestive of asthma was seen in three patients following two to six months of drug therapy of primary tuberculosis. There was a poor clinical response to administered bronchodilators. Bronchoscopy in all three revealed culture-negative mycobacterial caseating granulomas. Corticosteroid therapy resulted in good clinical response, with resolution of the asthmatic symptoms and improvement in the expiratory flow rates. In our opinion these patients are clinically compatible with a hypersensitivity response to mycobacteria following antituberculosis therapy and release of tuberculosis antigens. Corticosteroid therapy is appropriate in this form of tuberculous disease. PMID- 3349844 TI - Pleural effusions associated with hydrostatic and increased permeability pulmonary edema. PMID- 3349846 TI - The paradox of high-tech health care. Has our technology outstripped our ability to be ethical, cost effective and timely in its delivery? PMID- 3349845 TI - The performance of four pleural drainage systems in an animal model of bronchopleural fistula. AB - In order to compare the performance of four pleural drainage units (PDU [Emerson Post-Operative Pump, Pleur-Evac, Sentinel Seal, Thora-Klex]), we created an animal model of bronchopleural fistula that simulated the type of air leak seen clinically (mean maximal flow = 5 L/min). The PDU were tested at 0 cm (water seal), -20 cm and -40 cmH2O suction. Compared to water seal, -20 cmH2O suction significantly increased the ability of all four PDU to evacuate air via the chest tube and abolished small differences in chest tube air leak seen among the PDU at water seal. An increase in suction to -40 cmH2O did not significantly alter flow via the chest tube. Previously demonstrated differences among the PDU in handling large air flows were not seen in this lower flow model of bronchopleural fistula. However, because of their higher resistance, use of the Sentinel Seal and of the Thora-Klex was technically impractical even at air leaks of 4 to 5 L/min. PMID- 3349847 TI - Difficulties in evaluating coronary artery lesions. PMID- 3349848 TI - Pulmonary hypertension in a patient with rheumatoid arthritis. AB - A 53-year-old woman who had suffered from severe rheumatoid arthritis developed pulmonary hypertension. Her small arteries in the lung showed plexogenic arteriopathy with fibrous intimal hyperplasia. There was also vasculitis of the small arteries in other organs and mural thrombosis in the pulmonary stem and abdominal aorta. The plexogenic arteriopathy which was responsible for pulmonary hypertension appears to be the result of vasculitis in association with rheumatoid arthritis. PMID- 3349849 TI - Cardiac amyloidosis mimicking the echocardiographic appearance of obstructive hypertrophic myopathy. AB - A patient with rapidly progressing amyloidosis had cardiac involvement including the unusual echocardiographic appearance of both right and left ventricular outflow tract obstruction, previously unreported in this disease process. Echocardiographic findings were substantiated by autopsy findings of massive biventricular hypertrophy and amyloid deposition in the myocardium. PMID- 3349850 TI - Bilateral pulmonary artery stenosis associated with pericarditis. Results of surgery and follow-up by magnetic resonance imaging. AB - Reported is a patient with bilateral pulmonary artery stenosis which developed concurrently with an episode of idiopathic pericarditis. This association has been unreported previously. The stenosis was corrected surgically. Postoperatively, magnetic resonance imaging was used to follow the status of the pulmonary arteries serially. PMID- 3349851 TI - Noninvasive imaging of left coronary arteriovenous fistula. AB - We investigated a patient with coronary arteriovenous fistula (CAVF) by two dimensional echocardiography (2-DE), cardiac Doppler, cardiac catheterization and nuclear magnetic resonance (NMR). These investigations clearly showed the abnormal vascular structures. NMR is another valuable noninvasive and safe method of confirming the presence of a CAVF. PMID- 3349852 TI - Coronary dissection following chest trauma with systemic emboli. AB - Coronary artery dissection is a rare entity which occurs following blunt chest trauma, during coronary angiography and coronary bypass surgery, and spontaneously in the peripartum period. We report a young man who presented with recurrent systemic emboli following an asymptomatic anterior wall myocardial infarction associated with dissection of the LAD and mural thrombus three years earlier after sustaining blunt chest trauma. PMID- 3349854 TI - Significance of a curled central venous catheter tip. AB - A malpositioned central venous catheter can cause constant excessive pressure on one particular area of a central vein, thus leading to perforation and hydrothorax. The following is a case report of an iatrogenic hydrothorax caused by a malpositioned central venous catheter. The subtle sign of malposition is a slightly curled catheter tip. PMID- 3349855 TI - Hemoptysis during sexual intercourse. Unusual manifestation of coronary artery disease. AB - Sexual activity increases physiologic demands on the cardiovascular system. A patient with stable angina pectoris experienced recurrent bouts of hemoptysis caused by left ventricular failure that occurred only during sexual activity. Severe atherosclerotic coronary vascular disease was confirmed by cardiac catheterization. The patient underwent successful coronary artery bypass grafting; nine months after surgery, he is sexually active and symptom-free. PMID- 3349853 TI - Acute myocardial ischemia with prolonged left ventricular dyskinesia and mural thrombus formation in asymmetric septal hypertrophy. AB - A 52-year-old man had longstanding hypertension and asymemtric septal hypertrophy and normal major coronary arteries. His acute anterior wall ischemia gave rise to transient Q waves and septoapical dyskinesia, complicated by mural thrombus formation. Follow-up revealed a gradual and complete recovery of echocardiographic left ventricular function with total disappearance of mural thrombi and of electrocardiographic Q waves. Acute myocardial ischemia can cause prolonged electrical and mechanical stunning which can lead to mural thrombus formation. PMID- 3349856 TI - A misnomer. PMID- 3349857 TI - Purulent rhinosinusitis is also a cause of sepsis in critically ill patients. PMID- 3349858 TI - Detection of right pulmonary artery thrombosis by two-dimensional echocardiography. PMID- 3349859 TI - Criteria for steroid dependence. PMID- 3349860 TI - Study on tissue concentrations of antibiotics: bacampicillin in gingiva and maxillary bones. AB - 21 patients, whose age ranged from 17 to 60 years and who had not been previously treated with antibiotics or other drugs, received bacampicillin as a perioperative prophylaxis for minor operations in the oral cavity. Four oral doses of bacampicillin were administered: each dose of 800 mg every 12 h, and the last dose was administered 2 h before surgery. To assess bacampicillin serum concentrations two blood samples were collected from each patient: the first sample was obtained 1 h before surgery and the second one during surgery. Together with the second blood sample, small quantities of gingiva and bone were obtained from each patient to also assess the antibiotic concentrations in these tissues (microbiological method). The results show that bacampicillin reaches high concentrations in both the blood and tissues studied by us, and that a direct correspondence exists between blood and gingival and bone tissue concentrations. Furthermore, it should be noted that no postoperative infections developed in our patients. These results lead to the conclusion that bacampicillin appears to be a suitable drug in the therapy of dental infections. PMID- 3349861 TI - Cefoperazone compared with chloramphenicol in the treatment of typhoid fever. AB - The authors have conducted an open randomized study to compare the clinical efficacy and safety of cefoperazone with those of chloramphenicol in the treatment of typhoid fever. They studied 56 subjects (28 in each group), 36 males and 20 females, whose average age was 25.9 years. The diagnosis of typhoid fever was made when one of the at least three blood cultures performed was positive for Salmonella typhi and in the presence of a 'toxic'-like symptomatology and hyperpyrexia (39 degrees C). Moreover, several stool cultures were done and the signs and symptoms characteristic of the pathology in progress were monitored. Furthermore, the MICs of cefoperazone and chloramphenicol were determined for all the strains of S. typhi isolated in both groups. Cefoperazone was given at the mean dose of 2 g i.v. every 8 h, and chloramphenicol at the dose of 500 mg by oral route every 6 h. The results obtained were assessed statistically (Friedman's test and Fischer's test). The authors conclude that cefoperazone is as active as chloramphenicol, and the importance of this result should not be underestimated. PMID- 3349862 TI - Correlation between plasma and tonsillar levels of cefroxadine. AB - Serum and tonsillary tissue levels of cefroxadine, a new broad-spectrum cephalosporin, proving to be effective in several infections, particularly in the ENT ones, were measured in patients scheduled for tonsillectomy. Twenty patients (12 males, 8 females) aged between 11 and 25 years (mean 18.0 years) were given cefroxadine for 2 days (500 mg every 12 h), and on the 3rd day 500 mg of the drug was given before surgical operation. Tonsillar tissues were taken 2 h after dosing and blood samples before, 1, 2, 4 and 6 h after the drug administration in 8 out of 20 enrolled patients. Cefroxadine concentrations were measured according to microbiological methods. Cefroxadine tonsillary levels were 1.13 +/- 1.73 micrograms/g, approaching the MIC for sensitive bacteria. The time course of plasma levels is superimposable to previous studies. These findings suggest a rapid penetration of cefroxadine in tonsillar tissue and seem to confirm the clinical efficacy of the drug in ENT infections. PMID- 3349864 TI - [Motility disorders in inflammatory bowel diseases]. PMID- 3349863 TI - [Pathophysiologic principles and therapeutic consequences in motility disorders of the intestine]. PMID- 3349865 TI - [Simplification of surgical technics for venous catheterization in isolated cytostatic drug perfusion of the upper extremity]. PMID- 3349866 TI - [Retrograde invagination by a Braun anastomosis as a cause of outflow obstruction following Billroth II resection]. PMID- 3349867 TI - [A rare cause of intra-abdominal hemorrhage: rupture of a liver cyst]. PMID- 3349868 TI - [Aneurysm of the pancreaticoduodenal artery]. PMID- 3349869 TI - [A trichobezoar ileus]. PMID- 3349870 TI - [A rare teratoma of the retroperitoneum]. PMID- 3349871 TI - [Drug modification of gastrointestinal motility]. PMID- 3349873 TI - Telomeric DNA sequences differentially activated by heat shock in two Chironomus subspecies. AB - The patterns of puffing, transcription and protein synthesis under heat shock were analysed in polytene nuclei of Chironomus thummi piger, in comparison with those obtained in the closely related subspecies C. th. thummi. Most chromosomal heat shock puffs, as well as heat shock induced polypeptides, in C. th. piger paralleled those previously reported for C. th. thummi. Nevertheless, we found a striking difference in behaviour in the induction of telomeric Balbiani rings by heat shock in the two subspecies. Although homologous sequences were present at all the telomeres in both subspecies, they were not always transcriptionally activated by heat shock. The most frequently puffed telomeres were that of chromosome III R in C. th. thummi and that of chromosome IV R in piger. Transcription of the same sequences from both telomeric Balbiani rings (T-BR-III and T-BR-IV) occurred under heat shock. The enigmatic behaviour of telomeres and the functional significance of T-BRs are discussed in relation to possible equivalents in other Diptera. PMID- 3349872 TI - Treatment with sodium butyrate inhibits the complete condensation of interphase chromatin. AB - The effects of histone hyperacetylation on chromatin fiber structure were studied using direct observations with the electron microscope. Histone hyperacetylation was induced in HeLa cells by treatment with sodium butyrate, and the ultrastructure of control and of acetylated chromatin fibers examined after fixation at different stages of compaction. No differences between control and acetylated chromatin were seen when the fibers were partially unfolded (10 mM NaCl, 20 mM NaCl, 50 mM NaCl), but in 100 mM NaCl, control chromatin showed further compaction to the "30 nm" fiber, while hyperacetylated chromatin failed to undergo this final compaction step. These results strongly suggest that histone acetylation causes a moderate "relaxation" rather than complete decondensation of interphase chromatin fibers. The relationship of these findings to the increased DNase I sensitivity of acetylated chromatin, and to transcription and replication, is discussed. PMID- 3349875 TI - Radiologic studies of rectal evacuation in adults with idiopathic constipation. AB - A consecutive series of 58 patients with idiopathic constipation and 20 control subjects were studied by evacuation proctography and measurements were made of changes during rectal expulsion. A wide range was found in the control group. The anorectal angle, pelvic floor descent, and the presence or size of an anterior rectocele did not discriminate between the control and patient groups. Internal intussusception was rare. Among constipated patients, the only significant differences from normal were in the time taken to expel barium and the amount of barium remaining in the distal rectum. The majority of control subjects (15 of 20) evacuated most of the barium within 20 seconds whereas 45 of 58 constipated patients took a longer time. Using the area of barium on a lateral view of the rectum as a measure, 19 of 20 control subjects evacuated at least 60 percent of the barium from the distal 4 cm of the rectum compared with only 25 of 58 patients. A varying degree of defecatory impairment was thus established among many patients with constipation. The patients were subdivided into those with a normal or abnormal whole gut transit rate as an indication of colonic function, and those who did or did not need to digitally evacuate the rectum as a clinical manifestation of an anorectal disorder. No obvious differences were found between these subgroups using the parameters measured. PMID- 3349876 TI - Clinical-pathologic staging of large-bowel cancer. A report of the ASCRS Committee. AB - After surgical treatment in patients with large-bowel cancer, a prediction about the likelihood for cure remains uncertain despite the availability of several different types of staging systems. A committee of the American Society of Colon and Rectal Surgeons has reviewed the available data and concludes that future assessments of prognosis should be based on a combination of clinical and pathologic prognostic factors, using multivariate statistical techniques for the analysis. Although many important prognostic factors are known, there is much to learn about these and other items before a confident prediction of long-term outcome can be made. An extension of these methods should be possible to assist in prospective clinical decision-making based on clinical and investigational data. Such a system would be of particular value for patients with rectal cancer for whom cost-benefit relationships of alternative treatments can be so controversial. It is concluded that an accepted, standard nomenclature is required to reach both these objectives using large multicenter studies. PMID- 3349874 TI - Structure and function of Y chromosomal DNA. I. Sequence organization and localization of four families of repetitive DNA on the Y chromosome of Drosophila hydei. AB - The sequence organization of four different families of Y chromosomal repetitive DNA is characterized at three levels of spatial extension along the Y chromosome of Drosophila hydei. At the lowest level of resolution, DNA blot analysis of Y chromosomal fragments of different lengths and in situ hybridization experiments on metaphase chromosomes demonstrate the clustering of each particular sequence family within one defined region of the chromosome. At a higher level of resolution, family specific repeats can be detected within these clusters by crosshybridization within 10-20 kb long continuous stretches of cloned DNA in EMBL3 phages. At the highest level of resolution, detailed sequence analysis of representative subclones about 1 kb in length reveals a satellite-like head to tail arrangement of family specific degenerated subrepeats as the building scheme common to all four families. Our results provide the first comparative sequence analysis of three novel families of repetitive DNA on the long arm of the Y chromosome of D. hydei. Additional data are presented which support the existence of two related subfamilies of repetitive DNA on the short arm of the Y chromosome. PMID- 3349877 TI - Spontaneous and evoked coccygeal pain in depression. AB - Three hundred thirteen patients with signs of depression or spontaneous or evoked pain of coccygeal area were studied over six months. One hundred eighty (58 percent) had no spontaneous pain, 87 (28 percent) had moderate pain, and 46 (15 percent) a severe coccygodynia leading to consultation. In four of the latter group, no other sign of depression was found. Seventy-nine percent of the patients with spontaneous pain and 66 percent without spontaneous pain had coccygeal pain evoked by rectal digital examination (RDE). Seventy-one percent of the patients with spontaneous pain and 56 percent without spontaneous pain had paracoccygeal pain evoked by RDE. Among severely depressed patients (Group III), 76 percent had an evoked pain and 80 percent a coccygeal pain--either spontaneous or evoked. In 178 (57 percent), all signs disappeared when treated with various antidepressants in seven visits and within six months. Seven (2 percent) were failures; 44 (14 percent) were lost during follow-up; 84 (27 percent) did not return after the first consultation. After treatment in five patients was stopped, all signs recurred together and disappeared when adapted treatment was administered again. In 120 consecutive patients who had colonic roentgenologic examination and no depressive sign, two had coccygeal and muscular pain at rectal touch. A highly significant correlation was found between the following parameters: evoked pain and depressive status in noncoccygodynic patients, coccygodynia and evoked pain, coccygeal and paracoccygeal muscular pain. Severity of coccygodynia was not correlated with the number of depressive signs. Sex, age, and treatment efficiency were not correlated. The mechanism of depressive pain is discussed. RDE-evoked pain is proposed as an "objective" diagnostic sign for masked depression and as a means of evolution control. The frequency of the disease and efficiency of treatment are stressed. PMID- 3349878 TI - Risk factors and screening techniques in 500 patients with benign and malignant colon polyps. An urban community experience. AB - The authors have reviewed 13 years of experience with 500 patients who had 1240 polypoid lesions identified at colonoscopy. An analysis of these patients' symptoms, signs, and past histories prior to initial colonoscopy were collated by computer in order to provide useful information to help in early identification of patients with polyps and to define specific risk factors in patients with polypoid cancers (71 patients with 79 cancers). This study shows that the 500 patients with colon polyps, with and without cancer, are similar in all parameters measured. Their symptoms correlated poorly with the pathology or location of the polyp. Frequently unrelated symptoms brought the patient to the attention of their private physician. A significant high-risk group of patients identified were those with prior colon polyps and cancer. A positive family history of colon cancer was not common. Barium enema, the most common examination, was performed in 90 percent of patients and was the first test to diagnose polyps in 54 percent. Flexible sigmoidoscopy, only more recently available and performed in 20 percent of the patients, established a diagnosis of polypoid disease 96 percent of the time. This study supports screening for all adults above 40 years of age with flexible sigmoidoscopy and stool occult blood. PMID- 3349879 TI - Review of recurrent polyps and cancer in 500 patients with initial colonoscopy for polyps. AB - Five hundred patients with 1240 polyps removed by colonoscopy and polypectomy over a 13-year period are the subject of ongoing follow-up study. Ninety-three percent of the patients have been followed an average of 53 months with a recurrence rate of polypoid disease in 26 percent, of which approximately 7 percent demonstrated malignant changes. This compares to a rate of 7 percent metachronous cancer in patients with a malignancy demonstrated at any time in the past. The highest risk group for recurrence are patients with more than four polyps at initial colonoscopy, with a 59 percent recurrence rate. The following recommendations for follow-up are made: 1) Flexible sigmoidoscopy is adequate yearly follow-up if the original polyps are confined to the rectum and sigmoid. 2) Colonoscopy should be carried out the first year if the original polyps are beyond the rectum and sigmoid, and yearly until the colon is cleared of recurring lesions. 3) Colonoscopy is indicated in patients with cancer before surgery if possible; if not, within six months after resection. 4) Interval six-month examinations are indicated in patients with colon cancer and multiple synchronous polyps until the colon is cleared. 5) Large, sessile polyps resected piecemeal require a three-month follow-up until gone. 6) When the above conditions are met, colonoscopy at three-year intervals is adequate for long-term follow-up of neoplastic polyps to detect and prevent early malignancy. PMID- 3349880 TI - Flat adenoma and flat mucosal carcinoma (IIb type)--a new precursor of colorectal carcinoma? Report of two cases. AB - Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the "adenoma-carcinoma sequence." PMID- 3349881 TI - Hemorrhoidectomy in the patient with multiple or circumferential hemorrhoids. AB - A technique is presented that allows complete removal of hemorrhoids even when large hemorrhoids exist between the classic three major hemorrhoidal locations. Since the anorectal mucosa overlying these "interval" hemorrhoids is preserved, there is no increased tendency for stricture formation to occur. PMID- 3349882 TI - Comparison of stationary vs ambulatory 24-hour pH monitoring recording systems. AB - Twenty-four-hour pH monitoring of the esophagus is frequently performed to assess gastroesophageal reflux. We performed a prospective study to determine if results obtained from stationary and ambulatory pH recording systems are comparable. Two groups of patients were studied. Group I consisted of 12 patients monitored simultaneously by both a stationary and an ambulatory pH recording system, each system having a separate pH and reference electrode. In group II, in order to eliminate electrode variability, 10 patients were monitored simultaneously with both systems and a common single pH and reference electrode. In group I, significant correlations were found in six reflux parameters measured and in the 24-hr composite score (r greater than or equal to 0.8722). However, in three of the 12 patients, marked discrepancies were noted in the composite score calculated by the stationary and ambulatory recording systems. Small variations in the pH level recorded by different pH electrodes may have accounted for the discrepancies. In group II, where electrode variability was eliminated, a better correlation was noted between all parameters measured (r greater than or equal to 0.991), and no discrepancies were noted between calculated composite scores. We concluded that the stationary and ambulatory recording systems tested are comparable in measuring 24-hr esophageal pH. PMID- 3349884 TI - Gastric emptying in infants with gastroesophageal reflux. Measurement with a technetium-99m-labeled semisolid meal. AB - It is well established that liquid emptying occurs in the absence of motor activity of the stomach. In contrast, solid-phase emptying is controlled in part by antral peristalsis and is, therefore, a more precise indicator of gastric motility. We developed a semisolid, radionuclide gastric emptying test using rice cereal and technetium-99m-sulfur colloid to assess antral physiology in infants with vomiting. Computer-programmed mathematical models were used to determine the shape of a line that best fit our emptying data points. Linear, simple exponential [f = 2-(t/t1/2)], and power exponential [f = 2(t/t1/2)beta] patterns of emptying were calculated, where f is the fraction of the meal remaining in the stomach at time t, and t1/2 is the time when 50% of the meal has emptied and is a determinant of the shape of the curve. In infants with simple regurgitation (chalasia) and those with vomiting and failure to gain weight, we made statistical comparisons between gastric emptying patterns after analysis of the mean percentage of retained radionuclide at 120 min, calculated t1/2, and area under the curve. The coefficient of determination, R2, was calculated as an index of whether a curve provided goodness of fit to the data. Differences between groups of patients were statistically significant for all parameters of each mathematical model. However, higher coefficients of determination were noted in the power exponential model. The data suggest that the power exponential mathematical model provides the best analysis of the gastric emptying patterns for infants with chalasia and those with vomiting and failure to gain weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349883 TI - Effect of dilatation of peptic esophageal strictures on gastroesophageal reflux, dysphagia, and stricture diameter. AB - In 10 patients with peptic esophageal stricture the effect of esophageal dilatation on intraesophageal pH, stricture diameter, and dysphagia has been studied. Percentage of time during which intraesophageal pH was less than 4 and the number of reflux episodes per hour did not change significantly. Stricture diameter increased slightly, but consistently, from 7.0 +/- 0.5 mm to 9.1 +/- 0.5 mm (P less than 0.01) four days after dilatation, but was not significantly different from predilatation values after 12 weeks. Improvement in symptoms of dysphagia was striking (P less than 0.01) four days and six weeks after dilatation, but worsened again at 12 weeks (P = NS). It is unlikely that esophageal dilatation adversely affects the intraesophageal environment. PMID- 3349885 TI - Different implications of stigmata of recent hemorrhage in gastric and duodenal ulcers. AB - A prospective study was conducted to evaluate the prognostic value of stigmata of recent hemorrhage in patients with bleeding peptic ulcer. Of 193 patients suffering from peptic ulcer bleeding identified by emergency gastrointestinoscopy, 52 patients were found to have bleeding gastric ulcer (spurt 5, active oozing 9, fresh clot 11, black clot 17, protruding vessel 4, and clear base without stigmata 6); the other 141 had bleeding duodenal ulcer (spurt 5, active oozing 26, fresh clot 43, black clot 23, protruding vessel 15, and clear base without stigmata 31). Patient with continuous bleeding or rebleeding was grouped as unstable bleeders. The rate of unstable bleeders was 39.1% (continuous bleeding 23.9% and rebleeding 15.2%) in patients with gastric ulcer, compared to 9.0% (4.5% and 4.5%) in duodenal ulcer (P less than 0.001). The unstable bleeder rate of ulcers with spurt, active oozing, clot, and protruding vessel was 80%, 44%, 35.7%, and 0%, respectively, in patients with bleeding gastric ulcer; and 33.3%, 19.2%, 6%, and 0%, respectively, in patients with bleeding duodenal ulcer. The data suggest that the stigmata of recent hemorrhage, excluding protruding vessel, has prognostic significance in bleeding gastric ulcer but less in bleeding duodenal ulcer. PMID- 3349886 TI - Effect of glucagon on vagally induced gastric acid secretion in humans. AB - The effect of a physiologically relevant dose of pancreatic glucagon, 85 pmol/kg/hr, or saline on gastric acid secretion induced by modified sham feeding (chew and spit), was studied in 10 healthy volunteers. Gastric pH was held constant (pH 5.5) by intragastric titration. Glucagon infusion inhibited gastric acid secretion significantly, from 19.6 +/- 1.5 mmol H+ per hour during saline, to 10.4 +/- 1.4 mmol H+ per hour. Blood glucose increased during glucagon infusion and remained constant during saline infusion. Serum gastrin concentrations increased significantly by sham feeding, during saline as well as glucagon infusion, and no difference between the gastrin response during saline or glucagon infusion was found. Thus glucagon, in a physiologic dose, reduces vagally mediated acid secretion by a gastrin-independent mechanism. PMID- 3349887 TI - Effect of calcium carbonate and aluminum hydroxide on human intestinal function. AB - The effect of calcium carbonate (6 g daily) and of aluminum hydroxide (Amphojel, 7.2 g daily) on human gastrointestinal function was examined because these popular antacids have a documented effect on fecal fat, an undocumented association with constipation, and a putative ability to ameliorate cocarcinogenic effects of bile acids and fatty acids on colonic mucosa. Intake output studies were conducted over periods of three weeks during which time dietary intake was controlled (20 g fiber daily), and the order of treatment (control, calcium carbonate, aluminum hydroxide) was randomized. Neither calcium carbonate nor aluminum hydroxide altered the mean intestinal transit time of eight subjects. Calcium carbonate increased daily output of feces from 106 +/- 30 (SD) to 131 +/- 41 g, of fecal fatty acids from 7.9 +/- 1.4 to 16.8 +/- 5.4 mmol, and of fecal 3 alpha-hydroxy-bile acids from 411 +/- 223 to 769 +/- 505 mumol. Aluminum hydroxide increased daily output of feces to 143 +/- 43 g, of fecal fatty acids to 12.4 +/- 5 mmol, and of fecal bile acids to 735 +/- 592 mumol. Both Ca2+ and Al3+ precipitated deoxycholate when these ions were incubated in vitro. These observations help to explain how these two antacids may lower blood lipids and ameliorate the effects of fecal bile acids and fatty acids on colonic mucosa. PMID- 3349888 TI - Irritable bowel syndrome in Nigerians. AB - Twenty-six Nigerians with irritable bowel syndrome are reported. Twenty-three patients (88.46%) belong either to the middle or upper socioeconomic class; 16 patients (61.5%) had predominantly constipation. Six of the patients (23.1%) had their first symptoms before the age of 15 years. No sex preference is shown by this study. The most common symptoms are flatulence and abdominal pain, which is relieved by bowel motion, belching, and/or passage of flatus. Cow's milk, stress, and a local diet of beans are the most common aggravating factors, while another local high-fiber diet of cassava was found helpful in reducing the intensity and frequency of symptoms in some patients. PMID- 3349889 TI - Decreased colonic peptide histidine-methionine in idiopathic inflammatory bowel diseases. AB - The sequence for peptide histidine-methionine is present within the same preprohormone as vasoactive intestinal polypeptide. Since our previous study using radioimmunoassay had demonstrated significantly decreased colonic concentrations of vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis compared to normal colon, we determined the distribution and quantitation of peptide histidine-methionine. Fresh surgical specimens were dissected into mucosal-submucosal and muscularis externa layers prior to acid extraction and specific radioimmunoassay. One immunoreactive species that appeared to coelute with peptide histidine-methionine was separated by reverse phase high-performance liquid chromatography. Mucosal-submucosal concentrations of peptide histidine-methionine were significantly decreased in ulcerative colitis and Crohn's colitis, compared to those in normal colon. In normal ileum and colon, linear correlation analysis showed no relationship between patient age and tissue concentrations of peptide histidine-methionine. However, a parallel decrease in molar concentrations of peptide histidine-methionine and vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis was demonstrated by linear correlation analysis. These results are consistent with the hypothesis that peptide histidine-methionine and vasoactive intestinal polypeptide are colocalized within the same neural structures that have been altered in the idiopathic inflammatory bowel diseases. PMID- 3349890 TI - Human beta-glucuronidase. Measurement of its activity in gallbladder bile devoid of intrinsic interference. AB - Our purpose is to develop a standard method for preparing the bile for beta glucuronidase determination by removal of bile acids and conjugated bilirubin which interfere with its activity. The bile acids and conjugated bilirubin in their purified solutions and in the diluted gallbladder biles could be extracted completely with cholestyramine in powder form or tetrahexylammonium chloride (THAC) in chloroform or ethyl acetate. The enzyme was, however, partially precipitated with cholestyramine and denatured by chloroform but not by ethyl acetate. A standard procedure, therefore, includes extraction of the diluted gallbladder bile with THAC in ethyl acetate, followed by determination of the maximal velocity (Vmax) of the enzyme by a kinetic method employing phenolphthalein glucuronide as the substrate. The average Vmax of beta glucuronidase in the 20 normal gallbladder biles was 165 +/- 86 nmol/min/ml (mean +/- SD), a 23.5-fold increase over the activity before extraction. The measured activity represented the true activity of the enzyme in the bile for recovery of activity of the enzyme added to the bile was practically complete. PMID- 3349892 TI - Composition of intrahepatic calculi. Etiological significance. AB - Gallstones in intrahepatic (N = 42) and extrahepatic (N = 22) bile ducts and gallbladder (N = 23) were subjected to chemical analysis modified to suit the analysis of brown pigment stones with the aim of determining if stone location at surgery influenced stone composition. Dimethylsulfoxide-acetone-1 N HCl (90:9:1, v/v/v) was used to dissolve gallstone specimens. Intrahepatic calculi were divided into two groups, ie, nine cholesterol stones and 33 brown pigment stones. Cholesterol stones in the intrahepatic bile ducts had a similar composition to those in the gallbladder and extrahepatic bile ducts, suggesting a similar pathogenesis wherever formed throughout the biliary tract. Intrahepatic brown pigment stones contained significantly less bilirubin (P less than 0.001) and more cholesterol (P less than 0.05) by chi-square analysis than brown pigment stones found in the extrahepatic bile ducts, suggesting that the site of formation affects stone composition and modifies stone pathogenesis. PMID- 3349891 TI - Pattern of psychiatric morbidity and alcohol dependence in patients with alcoholic liver disease. AB - Fifty-six male patients with alcoholic liver disease were evaluated for the presence and severity of alcohol dependence and psychiatric illness using a severity of alcohol dependence questionnaire and research diagnostic criteria, respectively. Forty-three (76.7%) patients were found to be dependent; 26 (46.4%) moderately, and 17 (30.3%) severely. Patients with alcoholic hepatitis were significantly (P less than 0.05) more often found to be dependent than patients with alcoholic cirrhosis. Psychiatric morbidity was observed in 42 (75%) of the patients with alcoholic liver disease and 15 (26.7%) of the nonalcoholic cirrhotics. The difference was highly significant (P less than 0.01). The commonest disorders in patients with alcoholic liver disease were neuroses (33.0%), followed by affective disorders (26.8%). It was, however, not possible to ascertain whether psychiatric disorders antedated alcoholism or were secondary to it. Detection of moderate to severe dependence on alcohol and psychiatric morbidity in about three-fourths of the patients with alcoholic liver disease warrants an increased awareness and a multidisciplinary approach for the management of these patients. PMID- 3349893 TI - Intravascular volume in cirrhosis. Reassessment using improved methodology. AB - Previous studies of blood volume (BV) in cirrhosis have either not adjusted BV properly for body size; determined plasma volume from the dilution of labeled albumin 10-20 min postinjection, when some extravascular redistribution has already occurred; and/or not used the correct whole body-peripheral hematocrit ratio (0.82) in calculating whole BV from plasma volume and the peripheral hematocrit. We measured BV with attention to these considerations in 19 patients with cirrhosis and reexamined the determinants of vascular volume and the relationship between vascular volume and sodium retention. BV was calculated as plasma volume (determined from extrapolated plasma activity of intravenously injected [131I]+albumin at time 0) divided by (peripheral hematocrit X 0.82). The result was expressed per kilogram "dry" body weight, determined by subtracting the mass of ascites (measured by isotope dilution; 1 liter = 1 kg) from the actual body weight of nonedematous patients. Measured and expressed in this way, BV correlated strongly with esophageal variceal size (r = 0.87, P less than 0.05), although not with net portal, right atrial, inferior vena caval, or arterial pressure, and was significantly greater in patients with sodium retention as compared to patients without sodium retention. The principal modifier of vascular volume in cirrhosis is vascular capacity, which is probably mainly determined by the extent of the portasystemic collateral circulation. Increased vascular volume in patients with sodium retention as compared to patients without sodium retention supports the "overflow" theory of ascites formation. PMID- 3349894 TI - Human hepatocellular carcinoma tumor xenografts. Their androgen-receptor status and growth responses to castration. AB - Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivo studies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice. PMID- 3349895 TI - Pattern and duration of HBV DNA seropositivity in acute hepatitis B. AB - To determine the pattern and duration of HBV DNA seropositivity in acute hepatitis B, six patients were assessed during the incubation, clinical, and convalescent stages of their illness by DNA hybridization using a slot blot technique. Patients were identified by the detection of HBsAg nearly one month before the development of clinical and laboratory features of acute hepatitis (mean 22 +/- 4 days) and they were followed at one- to three-week intervals for 6 +/- 1 months. Each patient lacked antibody to delta virus. During the incubation period, HBV DNA was not detected in serum. At symptomatic onset, all were seropositive for HBV DNA and HBeAg. At peak biochemical disease, three patients had already cleared HBV DNA and five continued to harbor HBeAg. The duration of HBV DNA seropositivity was as short as one week. At the time of biochemical resolution, all patients had cleared HBV DNA, while four of five remained HBeAg positive. Clearance of HBeAg and HBsAg occurred 4 +/- 2 months after loss of HBV DNA. We conclude that HBV DNA is not detectable in serum during the early incubation period but that it is present at the onset of symptoms. Its duration in serum can be brief and clearance is possible by the peak of aminotransferase activity. HBV DNA usually disappears before HBeAg, and it is invariably lost by the time of biochemical resolution. Its detection in serum coincides with the clinical illness, but it may be missed unless sampling is done early in the clinical course. PMID- 3349897 TI - Biology of cell and membrane damage and repair. PMID- 3349898 TI - Strategies for rebuilding self-esteem for the cardiac patient. PMID- 3349896 TI - Effect of vagotomy on biliary-tract motor activity in the opossum. AB - In this study, we evaluated the effect of truncal vagotomy in the opossum on changes in gallbladder and sphincter-of-Oddi (SO) contractile activity that occur normally during fasting and after a meal. In six animals, bipolar electrodes were implanted on the SO, gastric antrum, duodenum, and jejunum. A catheter secured in the gallbladder fundus was used to monitor gallbladder volume. After control studies, truncal vagotomy and pyloroplasty were done in each animal. Before vagotomy, the SO exhibited cyclic changes in spike-burst rate, from 2 to 5/min, that were synchronized with corresponding phases of the duodenal MMC cycle. The gallbladder exhibited partial emptying during the second half of the duodenal MMC cycle with refilling during the first half of the next cycle. By two weeks after vagotomy, the MMC-related changes in SO and gallbladder contractile activity were normal. In contrast, vagotomy retarded the increase in SO spike-burst rate and delayed as well as diminished the pronounced gallbladder emptying that normally occurs after a meal. The same effects were observed for changes in SO and gallbladder activity induced by intraduodenal infusion of Isocal. After vagotomy, the SO and gallbladder exhibited exaggerated responses to intravenous infusion of CCK-OP or motilin. We conclude that truncal vagotomy in the opossum does not affect the fasting pattern of SO and gallbladder contractile activity, but it significantly alters the normal postprandial pattern of enhanced SO spike-burst rate and pronounced gallbladder emptying. The precise mechanism(s) whereby vagotomy produces these changes remains to be determined. PMID- 3349899 TI - Opening the postanesthesia care unit to visitors. PMID- 3349900 TI - Stress levels of ICU versus non-ICU nurses. PMID- 3349901 TI - SvO2 continuous monitoring techniques. PMID- 3349902 TI - Organization and nucleotide sequence of the gene encoding the beta-subunit of murine thyrotropin. AB - We constructed a murine genomic DNA library in lambda EMBL3 and have isolated and determined the nucleotide sequence of the murine thyrotropin beta-subunit (TSH beta) gene. The cloned gene was derived from a thyrotropic tumor and had no detectable rearrangements when compared to the murine TSH beta gene in total genomic DNA. The murine TSH beta gene is 5 kb in size and consists of five exons and four introns. The 5' untranslated region of the mRNA is encoded except for a single nucleotide by exons 1, 2, and 3. The protein-coding regions are encoded by exons 4 and 5 while the 3' untranslated region is entirely contained in exon 5. Primer extension analysis using an exon 1-specific primer was used to map the 5' end of the gene. Two transcriptional start sites are present in the murine TSH beta gene which appear to be positioned by two TATAAA sequences located 40 bp apart. In all, 99% of transcripts initiate at the downstream site. Transcription from both start sites is affected by thyroidal status in both murine pituitaries and in TtT97 thyrotropic tumors. Finally, sequences homologous with putative thyroid-responsive elements and cyclic AMP-responsive elements are present in the 5'-flanking region and may be important in regulating negative and positive effects on TSH beta gene expression. PMID- 3349903 TI - Complete sequence of cytochrome P450 3c cDNA and presence of two mRNA species with 3' untranslated regions of different lengths. AB - Two cDNAs (pLM3c 4.1 and pLM3c 6.1) coding for rabbit cytochrome P450 3c were sequenced. cDNA 4.1 (1768 bp) exhibits an open reading frame from nucleotides 74 to 1576 encoding the 501 amino acid residues of the entire protein. cDNA 6.1 (189 bp) appears to encode the last 24 amino acids. Comparative amino acid sequence analysis indicated that P450 PCN1, PCN2, and HLp from rat and man, were 70, 67, and 73% homologous, respectively, to P450 3c. According to the cytochrome P450 nomenclature, the P450 3c gene is termed P450IIIA4. Comparison of the nucleotide sequences indicated that cDNA 6.1 was 100% homologous to cDNA 4.1. However, whereas a poly(A) tract started 23 nucleotides after the AATAAA consensus sequence in cDNA 6.1, cDNA 4.1 had a 3' untranslated region extending 101 bp beyond the polyadenylation signal, which lacked poly(A). This observation is consistent with the previous finding that both cDNA 4.1 and 6.1 hybridized with two distinct species of poly(A)RNA (1700 and 1850 bases) from rabbit liver. The extreme 3'-end 79-bp fragment of cDNA 4.1 therefore was isolated by subcloning in pUC12 (clone p18-Rsa I) and used to probe Northern blots of poly(A)RNA from control and rifampicin-treated rabbit liver. In contrast to cDNA 4.1 and 6.1, p18 Rsa I cDNA hybridized only with the largest (1850 bases) mRNA species. We conclude that rabbit liver contains two P450 3c mRNA species differing in the length of their 3' untranslated region. PMID- 3349905 TI - High-resolution polyacrylamide gel electrophoresis of oligonucleotides using L histidine buffer. AB - We have found that 50 mM L-histidine pH 7.6 as a buffer for gel electrophoresis greatly improves the resolution of oligonucleotides less than 70 residues long on denaturing polyacrylamide gels. The histidine buffer increases spacing between DNA bands on the gel about twofold in comparison with a standard buffer (89 mM Tris-borate, 2 mM EDTA pH 8.3). In addition, low conductivity of the histidine buffer results in a threefold reduction of the electrophoresis time. Conditions for electrophoresis were optimized by varying both histidine and acrylamide concentrations. Other polycationic compounds, such as spermidine and ethylenediamine, were also tested for improved resolution of oligonucleotides. Several hypotheses as to the factors influencing the separation of DNA on gels are presented. PMID- 3349904 TI - A high-efficiency HeLa cell nuclear transcription extract. AB - A HeLa cell nuclear transcription extract that is approximately 20 times more efficient than standard HeLa cell transcription extracts was developed. Transcription of the strong adenovirus II major late promoter by this extract results in the synthesis of 1.5-4 molecules of product RNA per molecule of template, indicating that the extract is capable of multiple rounds of initiation. Standard HeLa cell nuclear extracts transcribe closed circular and linear adenovirus major late promoter templates with equal efficiency. In contrast, the new extract exhibits an increase of approximately twofold on transcription of a closed circular, as opposed to a linear, major late promoter template. PMID- 3349907 TI - Developmental and hormonal regulation of mRNAs for insulin-like growth factor II and steroidogenic enzymes in human fetal adrenals and gonads. AB - Insulin-like growth factor II (IGF-II) is regulated developmentally and hormonally in human fetal gonads and adrenals. The abundance of IGF-II mRNA is greatest in RNA from human fetal adrenals, followed by fetal liver, testis, placenta, and ovaries. Fetal testicular IGF-II mRNA decreases significantly with increasing gestational age, in parallel with our previous measurements of the mRNAs for the steroidogenic enzymes P450scc (cholesterol side-chain cleavage enzyme) and P450c17 (17 alpha-hydroxylase/17,20 lyase) (J. Clin. Endocrinol. Metab. 63, 1145, 1986). The abundances of P450scc and P450c17 mRNAs in cultured fetal testis cells rose 2.5-fold (p less than 0.01) and 9.2-fold (p less than 0.001), respectively, in response to 0.5 mM cAMP, but the abundance of IGF-II mRNA was not affected. This suggests that the IGF-II gene is regulated differently in fetal testes than it is in fetal adrenals, placenta, or adult granulosa cells, where we have previously shown that ACTH, cAMP, and gonadotropins, respectively, increase IGF-II mRNA accumulation (Proc. Natl. Acad. Sci. USA 84, 1590, 1987). Exogenously added IGF-I and IGF-II had no effect on mRNAs for P450c17 or P450c21 (21-hydroxylase), but decreased IGF-II mRNA in ACTH stimulated fetal adrenal cells. Thus, the IGFs appear to exert short-loop feedback inhibition on accumulation of IGF-II mRNA. PMID- 3349909 TI - Role delineation survey. PMID- 3349908 TI - Nursing diagnosis and wellness assessment. PMID- 3349906 TI - DNA amplification in vitro using T4 DNA polymerase. AB - We have evaluated in vitro DNA amplification by polymerase chain reaction using either T4 DNA polymerase or Klenow fragment of Escherichia coli DNA polymerase I. Both polymerases under optimal salt conditions permit efficient amplification of exon 3 of the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene from human genomic DNA and from plasmid containing the HPRT cDNA. DNA sequences amplified from human genomic DNA, using two 20-nucleotide primers flanking the ends of the exon, showed a marked difference between the two polymerases. T4 DNA polymerase yielded only the expected amplified DNA fragment, whereas Klenow fragment produced many lower-molecular-weight bands in addition to the expected DNA fragment. On the basis of the reported fidelity of in vitro DNA synthesis using Klenow fragment and T4 DNA polymerase, it is expected that the latter will create substantially fewer errors during the amplification process. For these reasons, T4 DNA polymerase should be particularly valuable for amplification of sequences present at a very low frequency requiring many cycles of amplification to be detected. PMID- 3349910 TI - Considerations in developing diabetes care teams. PMID- 3349911 TI - Islet pilots: an educational program for children with diabetes. PMID- 3349912 TI - Evaluation and treatment of organic impotence in the male with diabetes mellitus. PMID- 3349913 TI - The stepped approach to patient education. PMID- 3349914 TI - Development and evaluation of diabetes continuing education courses for health professionals: a synthesis of eight years of experience. PMID- 3349915 TI - Differences in patient knowledge about diabetes as a function of type of primary care physician. PMID- 3349917 TI - Writing reviews of manuscripts submitted for publication. PMID- 3349916 TI - Response of diabetic patients to a community-based education program. PMID- 3349918 TI - Comparative dissolution performance of internationally available piroxicam products. AB - Piroxicam is a widely used nonsteroidal antiinflammatory drug available worldwide under various trade names by several manufacturers. Only one brand of piroxicam (Feldene) is currently marketed in the U.S., and the United States Pharmacopeial Convention established an official dissolution requirement for piroxicam in 1985. The purpose of this study was to evaluate and compare the dissolution performance of several internationally available piroxicam products using the United States Pharmacopeia (USP) dissolution test for piroxicam capsules. Of 25 brands of piroxicam capsules evaluated, 72 percent of the brands failed to meet the USP requirement, several by a wide margin. Although there is no specific USP dissolution test for tablets, the test for capsules was applied to five different brands of piroxicam tablets, and 80 percent of the tablet brands tested failed to meet the USP requirement. Although comparative bioavailability studies would be required to establish any definitive relationship between dissolution test performance and bioavailability, the failure of most of these products to meet the USP requirement for dissolution indicates formulation differences that could result in altered bioavailability. The substantial differences in dissolution performance observed among the piroxicam oral dosage forms tested have implications concerning the equivalency and standards of multisource products available on the international market, and should be taken into account by health care providers worldwide. PMID- 3349919 TI - Establishment and evaluation of a serum cholesterol monitoring service in a community pharmacy. AB - A clinical pharmacy service providing blood cholesterol testing and consultation was implemented in a community pharmacy. In this pilot study, 27 patients each paid $10 to have a serum cholesterol determination. All subjects completed a questionnaire to determine attitude toward such a service, intention to use it in the future, and willingness to pay for its use. A posttest patient satisfaction questionnaire was completed after blood-level results were reported and discussed with the patient. All subjects stated that they were strongly in favor of such a service, that they would use it, and that they would pay an average of $11.60 for the test. On the posttest questionnaire, patients expressed strong satisfaction with various aspects of the service, and the amount that they were willing to pay increased significantly to $14.35. It is recommended that community pharmacies implement such patient-oriented services. PMID- 3349920 TI - Validation of the use of Bayesian analysis in the optimization of gentamicin therapy from the commencement of dosing. AB - A computer program based on the statistical technique of Bayesian analysis has been adapted to run on several microcomputers. The clinical application of this method for gentamicin has been validated in 13 patients with varying degrees of renal function by a comparison of the accuracy of this method to a predictive algorithm method and one using standard pharmacokinetic principles. Blood samples for serum gentamicin analysis were taken after the administration of an intravenous loading dose of gentamicin. The results produced by each method were used to predict the peak and trough values measured on day 3 of therapy. Of the three methods studied, Bayesian analysis, using a serum gentamicin concentration drawn four hours after the initial dose, was the least biased and the most precise method for predicting the observed levels. The mean prediction error of the Bayesian analysis method, using the four-hour sample, was -0.03 mg/L for the peak serum concentration and -0.07 mg/L for the trough level on day 3. Using this method the corresponding root mean squared prediction error was 0.60 mg/L and 0.36 mg/L for the peak and trough levels, respectively. PMID- 3349921 TI - Compatibility of clindamycin phosphate with aztreonam in polypropylene syringes and with cefoperazone sodium, cefonicid sodium, and cefuroxime sodium in partial fill glass bottles. AB - The stability and compatibility of clindamycin phosphate admixed with four beta lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours. PMID- 3349922 TI - Absorption of intraperitoneal antibiotics. AB - The treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) usually includes the repeated administration of intraperitoneal (ip) antibiotics. The initial segment of this study (15 noninfected CAPD patients) examined the ip administration of four structurally different agents that represent the common types of antibiotics prescribed for peritonitis: an aminoglycoside (tobramycin), a glycopeptide (vancomycin), a beta lactam (cefamandole), and an oxa-beta-lactam (moxalactam). Subsequently, 16 CAPD patients with peritonitis received either vancomycin (30 mg/kg) or cefamandole (1 g) in two liters of dialysate over a six-hour dwell period. Vancomycin and cefamandole were absorbed more rapidly in patients with peritonitis as indicated by a more rapid decline in dialysate concentrations, and higher serum concentrations that occurred earlier than in the noninfected patients. Although a higher percentage of the ip dose of vancomycin and cefamandole was absorbed during peritonitis, peak serum concentrations at the end of the drug administration dwell period were not significantly different. Numerous factors influence the absorption of ip antibiotics, including the dialysate drug concentration, the dwell period, protein binding, distribution volume, and presence or absence of peritonitis. PMID- 3349923 TI - Pharmaceutical marketing--rewriting the textbook. PMID- 3349924 TI - Documenting the clinical pharmacist's activities: back to basics. AB - The profession of pharmacy has applied the term "documentation" to count activities that more closely approximate descriptive protocols or administrative reports. This extended nonclinical use of the term documentation has resulted in the profession losing sight of a necessary step in the development, justification, and successful implementation of clinical pharmacy services. An instrument that helps to standardize the documentation of a clinical pharmacist's database, patient-care activities, and therapeutic plans is presented. This process, the pharmacist's workup of drug therapy (PWDT), consists of the following six interrelated steps: (1) establish a comprehensive patient-specific database; (2) identify patient-specific, drug-related problems; (3) describe desired therapeutic outcomes; (4) list all therapeutic alternatives that might produce the desired outcomes; (5) select the drug recommendation(s) that most likely will result in the desired outcomes; and (6) establish a plan for therapeutic drug monitoring that documents that desired effects occur and undesired effects are minimized. A formative method of documenting the clinical pharmacist's activities such as the PWDT must be functional on a daily basis in order to generate meaningful summative management reports. PMID- 3349925 TI - Green-top test tubes and lithium concentration. PMID- 3349926 TI - Drug use by children at a psychiatric clinic. PMID- 3349927 TI - Economic impact of AIDS. PMID- 3349928 TI - Therapeutic substitution in the health maintenance organization outpatient environment. AB - Health maintenance organizations (HMO) are growing in number as a cost-effective way of providing health care. In some, stringent formulary management policies including programs authorizing therapeutic substitution are practiced. Under this concept a drug that has been previously determined to be therapeutically equivalent to a second drug, even though it is not chemically equivalent to the prescribed drug, is automatically dispensed without contacting the prescriber. This study was undertaken to learn the extent and conditions under which therapeutic substitution is being practiced in the HMO setting. A survey was sent to all HMO in the U.S. inquiring into the operation of the pharmacy services. Specific focus was on the operation of the formulary and the policies and procedures being followed. The main goal was to learn how many programs authorize therapeutic substitution, what drugs are allowed, and what procedures are followed once the substitution is made. Of the 481 surveys sent out, 192 (40 percent) usable responses were received. Results indicate that 30.5 percent of HMO pharmacy plans allow therapeutic substitution. These programs were most likely to be of the staff-model or the group-model and least likely to be of the independent practice association type. HMO with an inhouse pharmacy more frequently had policies allowing therapeutic substitution than those using outside pharmacy services. PMID- 3349929 TI - Appropriateness of the use of serum lithium assays. AB - The performance of 222 lithium assays was studied in a psychiatric hospital to determine if their use was appropriate and therapeutically beneficial. Charts of all patients whose serum lithium levels were measured in a month were reviewed to determine whether the assays were indicated, whether they were performed correctly, and whether the dosage was adjusted appropriately. Of the assays reviewed, 16 percent were performed for inappropriate indications and 98 percent were drawn at correct times. Of 157 assays that should not have resulted in a dosage change, 8 changes were made; of 63 assays that should have resulted in a dosage change, only 23 changes were made. Inappropriate orders for assays cost the hospital +5016 per year. If routine serum lithium assay monitoring is changed to a three-month frequency, the total cost savings would be +16,632 per year. Clinical pharmacists with specialized knowledge of clinical pharmacokinetics should work with physicians and treatment teams in monitoring serum drug assays to ensure appropriateness of assay request, more complete interpretation of results, and proper follow up. PMID- 3349930 TI - A research program in pediatric pharmacy practice. PMID- 3349931 TI - Record linkage studies for postmarketing drug surveillance: data quality and validity considerations. AB - Large automated databases are the source of information for many record linkage studies, including postmarketing drug surveillance. Despite this reliance on prerecorded data, there have been few attempts to assess data quality and validity. This article presents some of the basic data quality and validity issues in applying record linkage methods to postmarketing surveillance. Studies based on prerecorded data, as in most record linkage studies, have all the inherent problems of the data from which they are derived. Sources of threats to the validity of record linkage studies include the completeness of data, the ability to accurately identify and follow the records of individuals through time and place, and the validity of data. This article also describes techniques for evaluating data quality and validity. Postmarketing surveillance could benefit from more attention to identifying and solving the problems associated with record linkage studies. PMID- 3349932 TI - On matters related to perpetual motion, pyramid schemes, the tooth fairy, and ingenuousness. PMID- 3349933 TI - Postgraduate pharmacy fellowships (1987-88). AB - During August and September 1987, the Brigham and Women's Hospital Pharmacy Services Department conducted its seventh annual nationwide survey of postgraduate pharmacy fellowships. There are 185 fellowships offered with 150 fellows at 53 sites. PMID- 3349934 TI - Delayed red neck syndrome with generic vancomycin. PMID- 3349935 TI - Cyclosporine binding to components in medication administration sets. PMID- 3349936 TI - Pharmacist not yet a drug advisor. PMID- 3349937 TI - Comment: importance of pharmacoepidemiology. PMID- 3349939 TI - [Familial hypertrophic obstructive cardiomyopathy]. AB - The diagnosis of hypertrophic obstructive cardiomyopathy in a 50-year-old man was confirmed by left-heart catheterization and echocardiography, the diagnosis having first been made some years earlier. Both his brother and his children have the same disease. The patient had several cardioversions for recurrent atrial fibrillation with a rapid ventricular rate. Because conservative treatment failed to give a satisfactory result, transaortic myotomy and myectomy were performed. Clinical examination eight months postoperatively showed that the patient's general condition had markedly improved, there was sinus rhythm, and the signs of left ventricular hypertrophy had regressed. PMID- 3349938 TI - [Immunotherapy of advanced pancreatic carcinoma with the monoclonal antibody BW 494]. AB - In the course of a phase I study monoclonal antibody BW 494 was injected i.v. at a dose of 180-340 mg to 18 patients with advanced ductal pancreatic carcinoma. The murine IgG1-antibody is directed against a pancreatic carcinoma-associated glycoprotein. The antibody inhibits the functions of human pancreatic carcinoma cells. Diffuse muscle pain, which disappeared spontaneously, was noted by two patients 14 days after injection. Other side-effects were anaphylactoid reactions in two patients 12 and 19 days, respectively, on repeat antibody infusions. This event led to changes in the administration schema so that the total amount was given within ten days, after which there were no further allergic side-effects. Terminal antibody half-life was 47.8 h (initial half-life 0.2 h). Human anti mouse antibodies in all eight patients tested for them developed within two to three weeks of the end of treatment. There were no tumour remissions. Progression of the tumour after treatment occurred in 12 patients (67%). In five patients the course was stable for at least three months after treatment, i.e. unchanged clinical status, unchanged tumour extent (CT), and stable tumour markers (CEA, CA 19-9) in serum. One female patient with a T3N1M0 carcinoma has so far lived for 16 months in full employment. The results justify the use of the monoclonal antibody in future controlled trials. PMID- 3349940 TI - [Hemodilution in cerebral ischemia]. PMID- 3349942 TI - [Surgery and AIDS]. PMID- 3349941 TI - [Hemoglobin A1 in kidney failure]. PMID- 3349943 TI - [Is irritable bowel syndrome a psychosomatic disease?]. PMID- 3349944 TI - [Long-term course of chronic polyarthritis under basic drug therapy]. AB - A retrospective analysis was undertaken of 31 patients with classical or proven chronic rheumatoid arthritis (CRA) who had been on a regimen of basic medication (gold salts, D-penicillamine, chloroquine, azathioprine--alone or in combination). Disease activity was checked by clinical, biochemical, immunological and radiological criteria. The laboratory results could not be altered by the basal medication and there was no relationship with the clinical and radiological findings, except for immunological results. None the less, the clinical symptoms improved under basal medication, even though the functional index got worse. The degree of joint destruction at the beginning and end of the observation period was markedly higher for seropositive than sero-negative cases, without significant differences in the rate of progression of joint destruction. Thus, definite long-term remission was achieved regarding the inflammatory changes but not the progressing joint destruction. PMID- 3349945 TI - [Psychosomatic aspects of irritable bowel syndrome. Specificity of clinical symptoms, psychopathological features and motor activity of the rectosigmoid]. AB - The clinical symptoms of patients with the irritable bowel syndrome (ICS) frequently do not differ according to present findings from those of patients with lactose malabsorption. To test this observation further in a gastroenterological out-patient clinic, the authors compared the clinical symptoms, psychological features and motor activity in the rectosigmoid in 20 patients with ICS and 21 with lactose malabsorption. It was found that the intestinal symptoms, intestinal motor activity and psychopathology of patients with ICS was nonspecific and occurred equally frequently as those in the malabsorption patients. This casts doubt on the view that psychological factors play a role in the pathogenesis of ICS. PMID- 3349946 TI - [Digitalis therapy in chronic heart failure. Digitoxin in patients in sinus rhythm pretreated with diuretics]. AB - Eight patients in sinus rhythm with chronic heart failure were studied. After individually adjusted six-week treatment with diuretics (hydrochlorothiazide triamtere and/or frusemide) all patients were clearly improved symptomatically. Subsequently they additionally received digitoxin for six weeks, 0.07-0.1 mg daily. Before and at the end of the digitoxin period cardiac volume was determined radiologically, echocardiography was performed and haemodynamic parameters determined at rest and on exercise via indwelling catheters. During digitoxin administration there was a slight increase in cardiac output from 4.63 +/- 0.82 to 5.05 +/- 0.98 l/min (P less than 0.1) at rest and from 7.22 +/- 1.94 to 7.79 +/- 2.59 l/min at rest. The mean values of all other haemodynamic parameters remained unchanged. These results suggest that in patients with chronic heart failure and sinus rhythm any clinical or haemodynamic improvement achieved will not be significantly bettered by digitoxin. PMID- 3349947 TI - [Repeated early systemic lysis in acute myocardial infarct with recurrent ventricular fibrillation]. AB - A 46-year-old man sustained an extensive acute inferoposterior myocardial infarction with cardiogenic shock. Recurrent ventricular fibrillation was controlled and enlargement of the infarct prevented by systemic thrombolysis, first begun in the ambulance and later twice repeated. Coronary angiography demonstrated isolated 50% stenosis of the circumflex branch in a left-dominant coronary circulation. Subsequent ventriculography demonstrated normal left ventricular function. PMID- 3349948 TI - [Bradycardia factitia]. AB - Repeated intake of 240-400 mg non-retard verapamil by a 26-year-old male nurse brought about interference dissociation resulting from extreme sinus bradycardia, passive AV nodal rhythm and hypotension. Because of a history of myocarditis a recurrence was suspected and an organic cause of the arrhythmia assumed at first, until its self-inflicted origin was discovered. The case demonstrates the need to consider self-medication, even if at first denied, in the differential diagnosis of arrhythmias even in the absence initially of any clear-cut pointers towards it. PMID- 3349950 TI - [Early diagnosis of systemic lupus erythematosus]. PMID- 3349949 TI - [Therapy of analgesic-induced chronic headache]. PMID- 3349951 TI - [Long-term results of endoscopic sphincterotomy in patients with gallbladder in situ]. AB - The place of endoscopic sphincterotomy (EST) as primary and sole invasive treatment was retrospectively analysed in 185 patients who had the procedure performed because of choledocholithiasis and/or stenosis of the papilla. EST was successful in 99.5%, with an early complication rate of 3.8%, an early mortality rate of 0.5% and an emergency operation rate of 0.5%. Freedom from stone in the choledochal duct or adequate bile flow was achieved in 94.1%. Late complications, on average 36.5 (6-75) months after the procedure, was 16.9%, late mortality 2.8% and operation rate for complications 5.6%. Even without stones in it the gallbladder was the cause of late complications in over 60% of cases. Comparison of results between operative treatment and EST indicated advantages of the former up to the age of 60 years, combined cholecystectomy and EST up to 70 years, while EST alone seems justified in older patients. PMID- 3349953 TI - [Informing about alternative possibilities of treatment]. PMID- 3349954 TI - [Biliary shockwave lithotripsy]. PMID- 3349952 TI - [Percutaneous transhepatic lysis of gallstones using methyl tert-butyl ether. Report on 15 patients]. AB - In 15 patients (13 women and two men) with cholesterol stones in the gall-bladder a special (Thistle) catheter was introduced into the gall-bladder under local anaesthesia by percutaneous transhepatic puncture. Methyl-tert-butyl ether, 2-15 ml, was injected via the catheter and removed again after 2 min. The number of stones per gall-bladder averaged 6.3 (1-20), size of stones 1.7 cm (0.5-2.8 cm), and duration of treatment 11.9 h (5-24 h). The stones dissolved in 13 patients (87%). In three patients stone debris remained: in one it was ultimately sucked out after reduction of the amount of debris with an EDTA-containing solution. The side effects of treatment--nausea and vomiting--were minor. In one patient there was a leak of bile from the gall-bladder after the procedure; a cholecystectomy was uneventfully performed. Another patient developed haemobilia which responded to conservative treatment. MTBE treatment has thus proved to be a successful and cheap method, low in side effects, in the treatment of patients with gall-stones. PMID- 3349955 TI - Nerve-sheath tumors of the head and neck. PMID- 3349956 TI - Tonsillar metastases from hypernephroma. PMID- 3349958 TI - Who operated on Max? PMID- 3349957 TI - Vallecular cyst in the newborn. PMID- 3349959 TI - Foreign body in the aeroesophageal tract. PMID- 3349960 TI - Supernumerary nasal teeth. PMID- 3349961 TI - Incidence of lacrimal obstruction following trauma to the facial skeleton. PMID- 3349962 TI - Quinsy tonsillectomy as the treatment of choice for peritonsillar abscess. PMID- 3349964 TI - Selected topics in emergency cardiology. PMID- 3349963 TI - Otitis media in the immunosuppressed child. PMID- 3349965 TI - Carbamazepine does not affect short-latency somatosensory evoked potentials: a longitudinal study in newly diagnosed epilepsy. AB - Somatosensory evoked potentials from median nerve stimulation were recorded in 12 patients with newly diagnosed epilepsy, before and after 1 year of treatment with carbamazepine. The plasma concentrations of the drug were consistently within therapeutic range. We assessed the latencies of the early components at the level of the cervical spine (N9 and N13) and on the parietal scalp (P14, N20, P25) and the interpeak latencies (N9-N13, N13-N20, P14-N20). None of the patients presented anomalies in any of the parameters, and there was no significant difference between the patient and control means or between the patient means before and after 1 year of treatment. PMID- 3349966 TI - Phenytoin levels in catamenial epilepsy. AB - We studied the fluctuations in phenytoin (PHT) levels during ovulatory and menstrual phases of the cycle, in eight patients with catamenial epilepsy and in eight age-matched controls. Pharmacokinetic studies of PHT were done in five patients with catamenial epilepsy. The difference in PHT levels during menstrual and ovulatory phase in catamenial group was 3.44 +/- 3.25 micrograms/ml as compared with 0.91 +/- 2.03 micrograms/ml in controls. The mean fall during menstrual phase was significant (p less than 0.05) in the catamenial group. There was also rapid though statistically nonsignificant clearance of PHT during menses as compared with the ovulatory period. It is presumed that the fall in plasma PHT levels during menses, though still within therapeutic range, may be responsible for catamenial exacerbation of epilepsy. PMID- 3349967 TI - Neuropsychological assessment of subjects with uncontrolled epilepsy: effects of EEG feedback training. AB - A battery of neuropsychological tests was administered at baseline, postcontrol period, and posttraining period to 24 drug-refractory subjects with epilepsy participating in a study of sensorimotor electroencephalographic (EEG) normalization feedback training. Results revealed the following. First, subjects exhibited significant baseline deficits in psychosocial, cognitive and motor functioning. Second, certain tests discriminated subjects before training who were subsequently above and below the median in seizure reduction following EEG training. Subjects who showed the greatest seizure reduction performed better on a test of general problem-solving ability but not on other cognitive tests and worse on tests involving strong motor components and were more intact psychosocially. These subjects also took significantly fewer medications in combination than did less successful subjects. Third, improvement on several measures occurred following participation in the study. Cognitive and motor functioning improved only in subjects with the greatest seizure reduction and only after actual training as opposed to control conditions. Psychological functioning, as measured by the Minnesota Multiphasic Personality Inventory (MMPI) improved in both outcome groups. MMPI improvement, unlike cognitive improvement, was as likely to occur after control conditions, when seizure reduction had not yet occurred, as after EEG training. Thus, MMPI changes apparently reflected the nonspecific benefits of participation in this study. PMID- 3349968 TI - MMPI indices in the identification of patients evidencing pseudoseizures. AB - Data are presented on the clinical utility of two Minnesota Multiphasic Personality Inventory (MMPI) indices, the Pseudo-Neurologic (Pn) Scale developed by Shaw and Matthews and the configural rule system developed by Wilkus et al. for the prediction of pseudoseizures. Particular attention is given to base rates, hit rates, and error rates in the analyses. Only the configural rule system was found to be of clinical value in ruling out the probability of pseudoseizures. PMID- 3349969 TI - Paroxysmal "feeling of somebody being nearby". AB - Several days after a right temporal lobectomy for an astrocytoma, a patient experienced a paroxysmal feeling that somebody was nearby. This spontaneous phenomenon has only rarely been reported in the epilepsy literature but has been reported to be evoked by electrical stimulation of the right amygdala. Despite the rarity in the literature, such unusual experiential phenomena probably are seen more frequently in clinical practice. PMID- 3349971 TI - The utility of cerebrospinal fluid examination in patients with partial epilepsy. AB - The initial evaluation of patients with seizure disorders frequently includes cerebrospinal fluid (CSF) examination in order to identify an underlying cerebral lesion. With increasing use of computed tomography (CT) scanning to detect cerebral neoplasms, the value of CSF examination has become less certain. The significance of mild CSF abnormalities in patients with a normal CT scan remains unknown. We reviewed the records of 95 patients with adult onset partial epilepsy whose initial evaluation included CSF examination and CT scan. A CSF abnormality not temporally related to convulsive seizure was seen in 24 patients (25%). The CSF study confirmed a clinically suspect subarachnoid hemorrhage in 4 patients. Isolated mild (49-106 mg/dl) increases in CSF protein were seen in 19 patients. Of these 19 patients, 8 had a structural lesion on CT scan. Clinical follow-up of the other 11 patients (mean 5 years) has revealed no evidence of a focal lesion or increasing seizure frequency. This suggests that in an adult population with partial epilepsy routine CSF examination may not be necessary and should be reserved for situations in which there is particular clinical indication. PMID- 3349970 TI - Clinically unsuspected cerebral infarction revealed by computed tomography scanning in late onset epilepsy. AB - The computed tomography (CT) scans of 132 patients with late onset epilepsy were compared with the CT scans of an age- and sex-matched control group. Patients with neurologic symptoms in addition to epilepsy, patients with a definite antecedent cause for epilepsy, and patients with tumours on CT scanning were excluded. Fifteen of the patients with epilepsy, as opposed to two of the controls, had infarcts on their CT scans (p = 0.003 Fisher exact test, two tailed). In nine of these patients only lacunar infarcts were present. No patient had a history of stroke. We concluded that cerebrovascular disease was the major underlying contributory factor to the development of epilepsy in these patients. Twelve of the 15 patients were aged greater than 60 years, representing 21% of the patients in this age group. There was no difference between the epileptic patients and controls in the presence of clinical features of systemic vascular and cardiac disease. CT scan evidence of cerebral atrophy was as common in the control subjects as in the patients with epilepsy. PMID- 3349972 TI - A NATO International Advanced Research Workshop on Frontal Lobe Seizures and Epilepsies. Paris, France, November 1-5, 1987. Abstracts. PMID- 3349973 TI - Comparison of health of occupants and characteristics of houses among control homes and homes insulated with urea formaldehyde foam. I. Methodology. AB - The methodology of a study in which a comparison is made of the health and house characteristics of the occupants of 231 control homes and 571 houses containing urea formaldehyde foam insulation (UFFI) is described. All homes and occupants were examined on two occasions separated by an interval of 12 months, during which two-thirds of the UFFI houses performed remedial work. The occupants were examined using a health questionnaire and a series of objective tests including pulmonary function, nasal airway resistance, sense of smell, nasal surface cytology, and patch tests. The houses were assessed using a questionnaire and measurements of indoor formaldehyde and carbon dioxide levels. No obvious bias has been identified in this survey with respect to the representativeness of the population studied, the classification of the UFFI and control groups, and the input from both the respondents and observers. The symptom responses made by individuals within the same households were not correlated. Quality control assessment of the objective health tests and formaldehyde sampling and assays demonstrated that these procedures remained stable over the two phases of the study, with the exception of the expected decrease in the pulmonary flow rates over 1 year and a small unexpected increase in the forced vital capacity and the forced expiratory volume in 1 s. PMID- 3349975 TI - Modeling mortality fluctuations in Los Angeles as functions of pollution and weather effects. AB - Linear and nonlinear models are used to investigate possible associations between mortality and pollution and weather effects in Los Angeles County. State-space modeling and time and frequency domain regressions are used to modify the data base and to isolate significant weather factors and pollutants associated with increased daily mortality. Nonparametric and parametric regression methods are used to develop nonlinear dose-response profiles relating mortality to temperature and to the statistically significant pollutants. A parametric nonlinear time series model involving linear and squared terms in temperature and the logarithm of pollution provides a reasonable predictive model. PMID- 3349974 TI - Comparison of health of occupants and characteristics of houses among control homes and homes insulated with urea formaldehyde foam. III. Health and house variables following remedial work. AB - This report describes the second survey of a group of 762 control and urea formaldehyde foam insulated (UFFI) houses performed following an interval of 1 year, after about two-thirds of the UFFI households either had their UFFI removed or performed other UFFI-related remedial work. The UFFI subjects who lived in remedial houses showed a decline in indicators of impaired health status, to roughly equalize with those whose houses were not altered; they continued to show a small excess of adverse health indicators relative to the controls, but at a somewhat lower level than seen in the first survey. This improvement was not associated with changes in indoor levels of formaldehyde. Weak exposure-response relationships were observed between formaldehyde and upper and lower respiratory symptoms, but mainly in the combined UFFI and control populations; these are interpreted as representing the contribution of background levels of formaldehyde to the prevalence of respiratory complaints in the general population. The principal findings of this study were primarily based on subjective variables, but most could be directly validated by objective measurements in the UFFI and control subjects. The support for a causal relationship between impaired health and living in a UFFI house is considered to be moderately strong. However the demonstrated adverse effects are generally minor in nature. PMID- 3349976 TI - Physical, morphological, and chemical studies of dusts derived from the machining of composite-epoxy materials. AB - This work (in three parts) inquires into whether respirable dusts derived from the machining of six composite-epoxy materials (e.g., aircraft industry) may pose a health risk to the operators. Dust samples representative of a variety of composites and structural components were aerodynamically sized and fractionated. Bulk and fractionated samples were examined by light and electron microscopy and analyzed chemically by thermogravimetry (TGA), gas chromatography (GC) and mass spectrometry (MS). Relative fractions of respirable to total mass of bulk samples were less than 3%; aerodynamic diameters of fractionated particles ranged from 0.8 to 2.0 microns. By microscopy, bulk particles ranged from 7 to 11 microns in diameter, with mean aspect ratios from 4 to 8:1. Mean diameter of fractionated particles was 2.7 microns. By TGA, weight losses were negligible below 250 degrees C and variable but elevated at temperatures up to 860 degrees C. In assays of vapors released at 250 degrees C, GC/MS indicated a variety of compounds in different amounts for each sample. We conclude that under the present machining protocols, dusts at the tool face contained few particles of respirable size with no evidence of splitting of fibers longitudinally and were of a low volatilizable chemical content. Overall, composites were judged to be well cured and thermally stable. PMID- 3349978 TI - Oxygen uptake as related to work rate increment during cycle ergometer exercise. AB - We postulated that the commonly observed constant linear relationship between VO2 and work rate during cycle ergometry to exhaustion is fortuitous and not due to an unchanging cost of external work. Therefore we measured VO2 continuously in 10 healthy men during such exercise while varying the rate of work incrementation and analyzed by linear regression techniques the relationship between VO2 and work rate (delta VO2/delta wr). After excluding the first and last portions of each test we found the mean +/- SD of the delta VO2/delta wr in ml.min-1.W-1 to be 11.2 +/- 0.15, 10.2 +/- 0.16, and 8.8 +/- 0.15 for the 15, 30, and 60 W.min-1 tests, respectively, expressed as ml.J-1 the values were 0.187 +/- 0.0025, 0.170 +/- 0.0027 and 0.147 +/- 0.0025. The slopes of the lower halves of the 15 and 30 W.min-1 tests were 9.9 +/- 0.2 ml.min-1.W-1 similar to the values for aerobic work reported by others. However the upper halves of the 15, 30, and 60 W.min-1 tests demonstrated significant differences: 12.4 +/- 0.36 vs 10.5 +/- 0.31 vs 8.7 +/- 0.23 ml.min-1.W-1 respectively. We postulate that these systematic differences are due to two opposing influences: 1) the fraction of energy from anaerobic sources is larger in the brief 60 W.min-1 tests and 2) the increased energy requirement per W of heavy work is evident especially in the long 15 W.min 1 tests. PMID- 3349977 TI - Neuromuscular and hormonal responses in elite athletes to two successive strength training sessions in one day. AB - Acute neuromuscular and endocrine adaptations to weight-lifting were investigated during two successive high intensity training sessions in the same day. Both the morning (I) (from 9.00 to 11.00 hours) and the afternoon (II) (from 15.00 hours to 17.00 hours) training sessions resulted in decreases in maximal isometric strength (p less than 0.01 and less than 0.05), shifts (worsening) in the force time curve in the absolute scale (p less than 0.05 and ns.) and in decreases in the maximal integrated EMG (p less than 0.01 and less than 0.05) of the selected leg extensor muscles. Increases in serum total (p less than 0.05) and free testosterone (p less than 0.01) and in cortisol (p less than 0.01) concentrations were found during training session II. These were followed by decreases (p less than 0.001 and p less than 0.01 and ns.) in the levels of these hormones one hour after the termination of the session. The responses during the morning training session were different with regard to the decreases in serum total testosterone (p less than 0.05), free testosterone (ns.) and cortisol (p less than 0.05). Only slight changes were observed in the levels of luteinizing hormone and sex hormone binding globulin during the training sessions. Increases (p less than 0.01) took place in somatotropin during both training sessions. The present findings suggest that high intensity strengthening exercises may result in acute adaptive responses in both the neuromuscular and endocrine systems. The diurnal variations may, however, partly mask the exercise-induced acute endocrinological adaptations in the morning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349979 TI - Comparison of isokinetic and isoinertial lifting tests as predictors of maximal lifting capacity. AB - This study compared the relationship between isokinetic lifting test (ILT) performance and a maximal operational lifting test (OLT) with that between an isoinertial progressive lifting test (PLT) and OLT. Fifty subjects performed the ILT, PLT and OLT after familiarization trials. OLT was defined as the weight of the heaviest crate that could be lifted to 1.34 m with a progressive, incremental test. ILT performance was the force generated during a single maximal simulated lift on an isokinetic dynamometer. PLT performance was the maximal weight lifted to 1.52 m with a progressive, incremental protocol on a weight stack. OLT was highly correlated with ILT (r = 0.96) and PLT (r = 0.97); the standard error was similar for both linear regression equations. The results demonstrate that a single maximal voluntary lift on an isokinetic dynamometer is as good a predictor of OLT as in the PLT presently used in military recruit centers. PMID- 3349980 TI - Serum iron and transferrin during an exhaustive session of interval training. AB - Conflicting data have been reported on "sports anaemia" and anaemia during physical training. Most of these results are of studies at rest before or after training. The aim of this investigation was to further study the profiles of serum iron (Se Fe) and transferrin (Se Tr), in 14 physically trained men (28 +/- 6 years) during an exhaustive interval training session. The 45 min Square-Wave Endurance Exercise Test (SWEET) was performed on a cycle ergometer. To the SWEET base, established as a % of individual VO2max, a peak of 1 min at VO2max was added every 5 minutes. Arterial blood samples were taken at rest, during the SWEET at the 14th, 15th, 29th, 30th, 44th and 45th minutes, just before and after the peaks, and at the 15th min of recovery. Lactate, acidity [H+], PaCO2, PaO2, Haematocrit (Hct), Haemoglobin (Hb), Se Fe and Se Tr were measured. After the SWEET, weight loss was 0.89 +/- 0.15 kg. Lactate and serum iron rose progressively at the base levels and at the peaks, while PaCO2 and bicarbonate fell progressively. Hct, [Hb], serum transferrin and [H+] increased significantly at the 14th min of SWEET and thereafter no change was observed. At the 45th min with respect to the value at rest, Se Fe increased as much as +32%, Se Tr +13% and [Hb] +8%. Haemoconcentration could explain the changes in Se Tr but not the total significant increase in Se, Fe, which moreover is not explained by acidosis [H+].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349981 TI - Effects of atropine and propranolol on the respiratory, circulatory, and ECG responses to high altitude in man. AB - In order to analyze the respiratory, cardiovascular, and ECG responses to acute hypoxic hypoxia, three experimental series were carried out in a randomized manner on 11 healthy, unacclimatized volunteers at rest during standardized stepwise exposure to 6000 m (PAO2 35.2 +/- 2.9 mmHg/4.7 +/- 0.4 kPa) in a low pressure chamber a) without (control), b) with propranolol, and c) with atropine combined with propranolol. The results show that hypoxic hyperventilation and alveolar gases are not affected by activation of the sympatho-adrenal axis or by parasympathetic withdrawal. Sympathetic activity, however, increases heart rate, stroke volume (pulse pressure), estimated cardiac output and systolic blood pressure, whereas decreased parasympathetic activity increases heart rate and estimated cardiac output, but lowers stroke volume. The fall in peripheral resistance, observed during progressive hypoxia in all three groups, is thought to be due to hypoxia-induced depression of the vasomotor center. At altitude catecholamine secretion and vagal withdrawal synergistically account in the ECG for the R-R shortening, the relative Q-T lengthening, the elevation of the P wave and the ST-T flattening. Probable direct hypoxic effects on the heart are the increase in P-Q duration and the minor but still significant depression of the T wave. It is concluded that at altitude increased sympatho-adrenal and decreased parasympathetic activity is without effect on hypoxic hyperventilation, but accounts for most of the cardiovascular and ECG changes. Diminution of sympathetic activity and imminent vagotonia arising after acute ascent to 6000 m probably reflect hypoxia of the central nervous system. PMID- 3349982 TI - Physical training and fasting erythrocyte activities of free radical scavenging enzyme systems in sedentary men. AB - Effects of 10 weeks of physical training on free radical scavenging enzyme systems in erythrocytes were investigated in 7 sedentary healthy male students. The training consisted of running over 5 km, 6 times/week. Their maximum oxygen uptake and 12 min walk-run performance increased significantly after training. Of the antioxidant enzyme systems examined in the erythrocytes, both catalase activity and concentration and total glutathione reductase (GR) activity also showed significant increases following the training. The erythrocyte GR activity coefficient also increased significantly. These results suggest that chronic aerobic exercise increases riboflavin requirements and has some positive effects on antioxidative processes. PMID- 3349983 TI - Food deprivation decreases the exertion-induced acid hydrolase response in mouse skeletal muscle. AB - Strenuous prolonged running causes muscle fibre necrosis in skeletal muscles. The muscle injury is associated with inflammation and a strong increase in the total activities of certain acid hydrolases a few days after exertion. The activity changes of acid hydrolases quantitatively well reflect the severity of histopathological changes during the myopathy (for review see Salminen, Acta Physiol Scand [Suppl 539] 1985). In this study male NMRI-mice were exposed to a protocol of fasting and refeeding together with or without a 6 h run on a treadmill at 13.5 m.min-1. The animals were killed 4 days after the exercise and samples from the red part of quadriceps femoris were analyzed for arylsulfatase (ASase) and beta-glucuronidase (GUase) activities. Starvation protocols did not affect ASase or GUase. Running caused a 3.2-fold increase in ASase and a 5.1-fold increase in GUase. If mice were exercised in the fasted condition a normal exercise response occurred in both activities, but when mice were exercised 2 days after the finish of fasting the exercise response was greatly diminished. Thus food deprivation followed by 2 days refeeding induces a protection against exercise myopathy in mice. The protection greatly resembles that induced by regular endurance training preceding strenuous prolonged exertion. PMID- 3349984 TI - Musculoskeletal capacity of middle-aged women and men in physical, mental and mixed occupations. A 3.5-year follow-up. AB - The musculoskeletal capacity of 44 women and 39 men, mean age 55.0 +/- 3.4 years, was studied at the beginning and end of a 3.5 year period. The measurements included anthropometrics, maximal isometric trunk flexion and extension strength, maximal isometric hand grip strength and back mobility. According to a job analysis the subjects were divided into three dominating work groups: physical, mental and mixed groups. The results showed significant changes in anthropometrics, maximal isometric muscle strength and in mobility. The body weight and body mass index among women and the body mass index among men increased significantly during the period. The body height and sum of the skinfolds had on the other hand decreased significantly for both women and men. Women showed significant decreases of 9% and 10% (p less than 0.05 and p less than 0.01) in isometric trunk flexion and extension strength, and an increase of 9% in back mobility (p less than 0.05). In mental work, most of the significant changes occurred among women. Men had significant decreases in isometric trunk flexion and extension, 22% and 16% respectively (p less than 0.001) and an increase of 13% in back mobility (p less than 0.001). The men doing physical work had most of the significant changes in musculoskeletal capacity. The results revealed accelerated changes in musculoskeletal capacity in middle-aged employees. PMID- 3349985 TI - Tocopherol mobilization during intensive exercise. AB - This work shows that the level of plasma tocopherol (vitamin E) which has free radical scavenging properties rises significantly during intensive exercise. It is proposed that mobilization of tocopherol could help to prevent lipoperoxidation phenomena occurring in exercising skeletal muscle. A hypothetical mechanism relating to a lipolysis effect is discussed to explain this mobilization. PMID- 3349986 TI - Lactate threshold and onset of blood lactate accumulation during incremental exercise after dietary modifications. AB - This study was designed to clarify the effects of dietary modifications on the lactate threshold (LT) and on the onset of blood lactate accumulation (OBLA) during progressive incremental exercise. Six healthy males volunteered for the study. Informed consent was obtained from every participant. The following protocol was administered to each subject on three occasions: a 48-h period of mixed dieting (53% carbohydrates, 30% lipids, 17% proteins) preceding the first exercise test, immediately followed by a 48-h period of either a carbohydrate rich (68% CHO, 23% lipids, 9% proteins) or a fat-rich (19% CHO, 57% lipids, 26% proteins) iso-caloric diet leading to the second exercise and separated from the third test by a 12-days period. Exercise tests were conducted on an electrically braked ergocycle, and consisted of a progressive incremental maximal exercise. Respiratory parameters were continuously monitored by an automated open circuit sampling system. Exercise blood lactate (LA), free fatty acids (FFA), glucose levels and acid-base balance were determined from venous blood samples obtained through an indwelling brachial catheter. Peak lactate values, workload and performance time were not significantly altered by imposed diets. Furthermore, dietary modifications had no significant effect on LT, OBLA fixed at 4 mmol and ventilatory threshold. Increased pH and FFA mobilization were observed with fat rich diet, while CHO-rich diet markedly increased the respiratory exchange ratio (R). It is concluded that LT and OBLA are not significantly altered by fat or CHO enrichment of diets. PMID- 3349987 TI - Iron deficiency caused by 7 weeks of intensive physical exercise. AB - The present study was designed to evaluate the effect of an intensive physical training program involving both isometric and isotonic activities on the body iron status of 8 females and 11 males (age 20 +/- 1 year). The training was carried out over a 7 week period and included 8 h of varying physical activities each day. Venous blood samples were obtained from the subjects prior to the beginning of the training, on day 2 and in weeks 2, 4, 6 and 7 of the program. Blood samples were analyzed for iron, ferritin and hemoglobin (Hb) concentrations, total iron binding capacity (TIBC) and red blood cell count (RBC). Iron levels of males and females decreased 65% after 2 weeks of training (p less than 0.001). At the end of the training program 5 males and 6 females had lower than normal iron values (less than 13.4 mumol.l-1). TIBC increased 25% in women and 18% in men following 2 and 4 weeks of training (p less than 0.001) and remained at this elevated level throughout the training period. Ferritin levels decreased 50% in both sexes after 4 weeks of exercise (p less than 0.05) and remained at this level until the end of the training. Hb and RBC decreased 8-10% in both sexes during the training period. In two of the women anemia occurred after 4 weeks of training. The development of latent iron deficiency in a substantial number of participants after a relatively short period of training is uncommon and may reflect the high intensity of exercise required in this program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349988 TI - Effects of training at simulated altitude on performance and muscle metabolic capacity in competitive road cyclists. AB - Differences between the effects of training at sea level and at simulated altitude on performance and muscle structural and biochemical properties were investigated in 8 competitive cyclists who trained for 3-4 weeks, 4-5 sessions/week, each session consisting of cycling for 60-90 min continuously and 45-60 min intermittently. Four subjects, the altitude group (AG), trained in a hypobaric chamber (574 torr = 2300 m above sea level), and the other four at sea level (SLG). Before and after training work capacity was tested both at simulated altitude (574 torr) and at sea level, by an incremental cycle ergometer test until exhaustion. Work capacity was expressed as total amount of work performed. Venous blood samples were taken during the tests. Leg muscle biopsies were taken at rest before and after the training period. AG exhibited an increase of 33% in both sea level and altitude performance, while SLG increased 22% at sea level and 14% at altitude. Blood lactate concentration at a given submaximal load at altitude was significantly more reduced by training in AG than SLG. Muscle phosphofructokinase (PFK) activity decreased with training in AG but increased in SLG. All AG subjects showed increases in capillary density. In conclusion, work capacity at altitude was increased more by training at altitude than at sea level. Work capacity at sea level was at least as much improved by altitude as by sea level training. The improved work capacity by training at altitude was paralleled by decreased exercise blood lactate concentration, increased capillarization and decreased glycolytic capacity in leg muscle. PMID- 3349989 TI - The danger of an inadequate water intake during prolonged exercise. A novel concept re-visited. AB - To prevent thermal injuries during distance running, the American College of Sports Medicine proposes that between 0.83 and 1.65 l of water should be ingested each hour during prolonged exercise. Yet such high rates of fluid intake have been reported to cause water intoxication. To establish the freely-chosen rates of fluid intake during prolonged competitive exercise, we measured fluid intake during, body weight before and after, and rectal temperature after competition in a total of 102 runners and 91 canoeists competing in events lasting from 170-340 min. Fluid intakes during competition ranged from 0.29-0.62 l.h-1; rates of water loss ranged from 0.69-1.27 l.h-1 in the runners; values were lower in the canoeists. Mean post-race rectal temperatures ranged from 38.0-39.0 degrees C. There was no relationship between the degree of dehydration and post-race rectal temperature. We conclude that hyperthermia is uncommon in prolonged competitive events held in mild environmental conditions, and that exercise intensity, not the level of dehydration, is probably the most important factor determining the postexercise rectal temperature. During prolonged exercise in mild environmental conditions, a fluid intake of 0.5 l.h-1 will prevent significant dehydration in the majority of athletes. PMID- 3349990 TI - Improved thermoregulation caused by forced water intake in human desert dwellers. AB - Residents of the Negev desert in Israel sustain a mild state of dehydration. Low, concentrated urine outputs, high incidence of kidney diseases and high hematocrit ratios characterize this population. Educational programs to increase the awareness of the population to the dangers of dehydration have undoubtedly failed. It was our purpose to see whether forced increased drinking will affect the above variables. Ten healthy subjects were asked to double their normal voluntary water intake without (phase II) and with salt supplements (50 mM NaCl, 20 mM KCl) (phase III), for one week. After phases II and III significant increases in body masses, decreased concentrations of serum proteins, hemoglobin, hematocrit ratios and serum osmolalities were found. No significant changes were found in the concentrations of sodium and potassium in the serum. At the end of each phase, the subjects were asked to exercise on a bicycle ergometer for 60 min at 50% VO2max in a heated chamber at 45 degrees C, and 30%-50% relative humidity. Experiments were terminated if and when heart-rates exceeded 180 bpm or the rectal temperature increased to 39 degrees C. After both experimental phases, subjects increased their tolerance to heat, extending the exercise periods by 25% and 30%. Compared with their starting levels, hematocrit ratios, serum proteins and hemoglobin concentrations increased in phases II and III while no changes were recorded in the control period (phase I). It is suggested that spontaneous voluntary water drinking in desert dwellers is not enough to achieve a true state of "euhydration". PMID- 3349991 TI - Measurement of torso skin temperature under clothing. AB - The influence of clothing on skin temperature distributions of the torso was investigated during and after cold exposure. Volunteers were cooled for one hour at 5 degrees C while wearing clothing designed to have insulation which was intended to be relatively uniformly distributed. Three different thicknesses of clothing were used. Following thermistor measurements of skin temperatures during the cold exposures, clothing was quickly removed from the upper parts of the body to enable thermographic investigations of the temperature distributions of the front of the bare torso. The evolution of temperature distributions were then studied at different ambient temperatures (5 degrees C and 20 degrees C) as a function of the thickness of the insulation which had previously been worn. The patterns of the temperature distributions, and the range and standard deviation of torso temperatures were all found to be relatively constant in spite of the different thicknesses of clothing worn or in the time-variant mean torso temperatures which resulted. The front torso sites normally used for the determination of mean skin temperatures were found to be on portions of the torso which were cooler than the surrounding regions. It was concluded that a site midway between the umbilicus and a nipple yields a more accurate estimate of mean torso temperature in the conditions of the present study. PMID- 3349992 TI - Blood lactate accumulation in intermittent supramaximal exercise. AB - Blood lactate accumulation rate and oxygen consumption have been studied in six trained male runners, aged 20 to 30 years. Subjects ran on a treadmill at a rate representing 172 +/- 5% VO2max for four 45 s sessions, separated by 9 min rest periods. Oxygen consumption was measured throughout. Blood lactate was determined in samples taken from the ear and VO2 was measured at the end of each exercise session, and two, five and nine minutes later. After the fourth exercise session, the same measurements were made every five min for 30 min. 4 subjects repeated a single exercise of the same type, duration and intensity and the same measurements were taken. With repetitive intermittent exercise, gradual increases in blood lactate concentration [( LA]b) occurred, whereas its rate of accumulation (delta[LA]b) decreased. The amount of oxygen consumed during each 45 s exercise session remained unchanged for a given subject. After cessation of intermittent exercise, the half-time of blood lactate was 26 min, whereas it was only 15 min after a single exercise session. VO2 values, on the other hand, returned to normal after 15 to 20 min. All other conditions being equal, the gradual decrease in delta[LA]b during intermittent exercise could be explained if the lactate produced during the first exercise session is used during the second period, and/or if the diffusion space of lactate increases. The diffusion space seems to be multi-compartmental on the basis of half-time values noted for [LA]b after intermittent exercise, compared with those noted after a single exercise session.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349993 TI - External load can alter the energy cost of prolonged exercise. AB - The present study was undertaken to examine the energy cost of prolonged walking while carrying a backpack load. Six trained subjects were tested while walking for 120 min on a treadmill at a speed of 1.25 m.s-1 and 5% elevation with a well fitted backpack load of 25 and 40 kg alternately. Carrying 40 kg elicited a significantly higher (p less than 0.01) energy cost than 25 kg. Furthermore, whereas carrying 25 kg resulted in a constant energy cost, 40 kg yielded a highly significant (p less than 0.05) increase in energy cost over time. The study implies that increase in load causes physical fatigue, once work intensity is higher than 50% maximal work capacity. This is probably due to altered locomotion biomechanics which in turn lead to the increase in energy cost. Finally, the prediction model which estimates energy cost while carrying loads should be used with some caution when applied to heavy loads and long duration of exercise, since it might underestimate the actual energy cost. PMID- 3349995 TI - The effects of a glycogen loading regimen on acid-base status and blood lactate concentration before and after a fixed period of high intensity exercise in man. AB - Six healthy male subjects exercised after an overnight fast for a fixed 3 min period at a workload equivalent to 100% of their maximal oxygen uptake (VO2max) on 3 separate occasions. The first test took place after subjects had consumed a mixed diet (43 +/- 3% carbohydrate (CHO), 41 +/- 5% fat and 16 +/- 3% protein) for 3 days, and was followed 2 h later by prolonged cycling to exhaustion at 77 +/- 3% VO2max to deplete muscle glycogen stores. Following this, subjects consumed a low CHO diet (4 +/- 1% CHO, 63 +/- 5% fat and 33 +/- 6% protein) for the remainder of the day and for the subsequent 2 days; on the morning of the next day a second high intensity test took place. Finally subjects followed a 3 day high CHO diet (73 +/- 7% CHO, 17 +/- 6% fat and 10 +/- 1% protein) before their last test. Acid-base status and selected metabolites were measured on arterialized-venous blood at rest prior to exercise and at intervals for 15 min following exercise. Prior to exercise, plasma pH and blood lactate concentration were higher (p less than 0.05) after the high CHO diet when compared with the low CHO diet. Pre-exercise plasma bicarbonate, blood PCO2 and blood base excess were all higher after the high (p less than 0.001, p less than 0.01, p less than 0.01 respectively) and normal (p less than 0.05, p less than 0.05, p less than 0.05 respectively) CHO diets when compared with the low CHO diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349996 TI - The influence of work intensity on postexercise proteinuria. AB - Fifteen men were studied during 100 m, 400 m and 3,000 m runs at maximal speed to determine total urinary protein and albumin excretion rates in relation to different distances of running. Venous blood lactate rose to 7.5 mmol.l-1 after the 100 m and 3,000 m events, while reaching 12 mmol.l-1 after the 400 m dash. Total urinary protein excretion increased to 330, 1640 and 565 micrograms.min-1 after the 100 m, 400 m and 3,000 m runs respectively, as compared with basal values (70 micrograms.min-1). In the meantime, albumin excretion increased respectively by 5, 25 and 18 fold of the resting values. The renal clearance of albumin increased to 0.84, 5.62 and 3.35 microliter.min-1 after the three runs, as compared with a mean value of 0.19 microliter.min-1 at rest. Exponential relationships (r = 0.85) were recorded between post-exercise venous lactate and albumin, and total protein excretion. The present work illustrates the major influence of the intensity of exercise (anaerobic glycolytic component), rather than its duration, on the excretion rate of urinary proteins. PMID- 3349994 TI - Exercise versus immersion: antagonistic effects on water and electrolyte metabolism during swimming. AB - Changes in blood composition, renal function, aldosterone and antidiuretic hormone (ADH) concentrations were investigated in 10 untrained male subjects when swimming (60 min at a heart rate of about 155 beats.min-1, water temperature 28 degrees C) and during the subsequent 3 h in a sitting position. Many specific effects of either exercise or immersion were abolished or attenuated; no significant changes in plasma aldosterone, [ADH], [K+], [Cl-], or of urinary volume, glomerular filtration rate, free water or osmolar clearance were observed. The urine was diluted resulting in lowered [Na+]. In blood some quantities which are only slightly influenced by immersion increased during swimming ([Na+], [Lac-], [H+], osmolality, [creatinine]). Exercise induced plasma volume loss, calculated from increasing [Hb], was small (110 ml), probably because interstitial fluid enters the vascular space during the initial phase of immersion. One might anticipate that the training effects on fluid and electrolyte metabolism and circulation are different when swimming and when performing endurance sports on land. PMID- 3349997 TI - Changes in red cell density and related indices in response to distance running. AB - The red cell population in peripheral venous blood was characterised in 7 young males before and up to 16 days after a 21.1 km road race. There was a 1.9 +/- 2.4% (mean +/- SD) reduction in plasma volume immediately post race (p less than 0.05), an increase in serum osmolality from 277 +/- 4 mOsm.kg-1 to 291 +/- 14 mOsm.kg-1 (p less than 0.05) and a reduction in red cell water (64.4 +/- 0.3% to 63.4 +/- 0.4%, p less than 0.001). The latter was consistent with alterations in the manually derived MCV and MCHC values although the same Coulter derived values were unaltered. A concomitant increase in median red cell density in whole blood (1.1045 +/- 0.0009 g.ml-1 pre race to 1.1057 +/- 0.012 g.ml-1 immediate post race, p less than 0.05) was recorded by centrifugation through phthalate esters of different density. The changes in creatine content of the red cells suggested that during the race younger cells were released into the circulation but that 24 h to 72 h after the race the mean red cell age had increased. Similarly, fractionation of the red cells on discontinuous Percoll density gradients indicated that the cell population was significantly denser in all post race samples up to 72 h but had normalized by a 16 day sample; the osmotic fragility was similarly affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3349998 TI - Molecular cloning and expression of salmon prolactin cDNA. AB - Prolactin was purified from chum salmon pituitaries. It was resolved into two variants by reverse-phase high-performance liquid chromatography. A cDNA library was prepared from Pacific chinook salmon pituitaries. Salmon prolactin gene was screened using a synthetic oligonucleotide based on partial protein sequence. A positive clone (PRL-10) was identified and sequenced. It is a full-size clone containing 1.1 kb and coding for a preprolactin of 211 amino acids. A modified prolactin plasmid (PRL-10A), in which the 5' untranslated sequence and the nucleotide sequence coding for the signal peptide of prolactin were deleted, was reconstructed into an expression vector using the heat-inducible lambda pL promotor. Mature prolactin, a single polypeptide of 22 kDa, was efficiently expressed in the bacteria at an elevated temperature. PMID- 3349999 TI - Site-site interactions in EF-hand calcium-binding proteins. Laser-excited europium luminescence studies of 9-kDa calbindin, the pig intestinal calcium binding protein. AB - Europium(III) binding to 9-kDa calbindin from pig intestines was studied by direct excitation of the 7Fo----5Do transition of the ion and by near-ultraviolet circular dichroic spectroscopy. Europium(III) binding is clearly biphasic. As with other lanthanides the C-terminal metal-binding site (site II) is filled first. The europium ion in this site gives an excitation spectrum with a single peak at 579.1 nm (peak 2). The occupation of the N-terminal site (site I) by europium gives excitation spectra that are pH-dependent and show a peak at 579.4 nm (peak 1a) at pH 5 which shifts to 578.7 nm (peak 1b) over the pH range 5-7. At pH 8.07 the fluorescence from europium in site I largely disappears because of weak binding, whereas that from site II is quenched by about 75% in spite of full occupancy of the site as shown by circular dichroic titration. There is a strong interaction between the two sites in spite of the very different affinities. The fluorescence from site II increases stoichiometrically with the addition not only of the first equivalent of europium, but also concomitantly with the fluorescence from site I upon addition of the second equivalent. Furthermore, when Eu1 calbindin is titrated with calcium the fluorescence at 579.1 nm is quenched by about 30% during the addition of one equivalent of calcium which fills site I. Subsequent titration with large excesses of calcium displaces europium from site II. The affinity of site II for europium is about 100 times that of calcium under these conditions. PMID- 3350000 TI - Differential mRNA stability to reticulocyte ribonucleases correlates with 3' non coding (U)nA sequences. AB - The stabilities of different mRNA species were analyzed in a reticulocyte lysate system under protein-synthesizing conditions. In all cases examined the relative mRNA degradation by reticulocyte ribonucleases as well as by the interferon modulated (2'-5') (A)n-dependent endonuclease correlated with the extent of (U)nA sequences within the 3' non-coding region. The experimental data presented indicate that according to their stabilities at least three major mRNA groups may be identified: (a) (U)nA-poor mRNAs (e.g. globin) are essentially stable and are only slightly degraded by the (2'-5')(A)n-dependent endonuclease; (b) mRNA species with intermediate (U)nA levels (e.g. Ig alpha and Ig mu heavy-chain mRNAs) are partially degraded by general ribonuclease activity and further degraded by the (2'-5')(A)n-dependent endonuclease and (c) (U)nA-rich mRNA species (such as c-myc and non-skeletal actin mRNAs) are inherently unstable and are extremely sensitive to degradation by general ribonuclease activity. A survey of mRNA nucleotide sequences demonstrated that without exception (U)nA-rich stretches appeared more frequently within the 3' non-coding region than in the coding or 5' non-coding regions. A comparison of 3' non-coding region sequences from 92 different mRNAs revealed that transiently expressed mRNAs, such as the interleukins, nerve growth factor, epidermal growth factor receptor, c-myc, c fos, c-myb and several other oncogenes as well as interferons alpha, beta and gamma were exceptionally (U)nA-rich. It is postulated that differential mRNA stability may be partly determined by the primary nucleotide sequence and in particular by (U)nA sequences within the 3' non-coding region. This may represent a novel post-transcriptional strategy employed by the cell to selectively retain or destroy discrete mRNA species. PMID- 3350001 TI - Members of the Drosophila HSP 70 family share ATP-binding properties. AB - In Drosophila, the hsp 70 family consists of a group of proteins of similar molecular masses (hsps 68, 70 and 72) that exist as multiple isoforms. In this report, it is shown that hsps 68, 70 and 72 from Drosophila cells can be purified by affinity chromatography on ATP-agarose. Furthermore it is demonstrated that the multiple members of the hsp 70 family, which accumulate in large amounts in the nucleus during a heat shock, can be specifically solubilized from the isolated nuclei fraction by ATP. One of the major cognate proteins (hsc 70) also shows similar behavior. These data suggest that most, if not all, of the related Drosophila hsps 70 possess, like their mammalian counterparts, an ATP-binding site which could be related to their function in the stress response. PMID- 3350002 TI - Regulation of translation and stability of an mRNA coding for a 40-kDa polypeptide in rat L6 muscle cells. AB - The mRNA coding for a 40-kDa polypeptide (P-40) was previously cloned and sub cellular distribution of this mRNA was examined in rat L6 myoblast cells under different conditions [Pramanik, S. & Bag, J. (1987) Eur. J. Biochem. 170, 59-67]. The translation of this mRNA was found to be regulated during differentiation of myoblasts. This mRNA was translated in proliferating myoblasts but not in the non dividing differentiated myotubes. We have further examined whether the mRNA present in the polysomal fraction of myoblasts and that in the free non-polysomal fraction in myotubes was identical by nuclease S1 mapping. The coding strand of the 600-base-pair PstI fragment of the recombinant clone was 3'-end-labeled with cordycepin 5'-[alpha-32P]triphosphate and hybridized with RNA from either myoblasts or myotubes. The results of these studies have shown that RNA from both preparations was fully able to hybridize with the probe DNA and, therefore, protected the 600-nucleotide-long fragment from nuclease S1 digestion, thus suggesting that the sequence of 600 nucleotides at 3' ends of both translationally active polysomal mRNA of myoblasts and repressed free mRNA of myotubes are identical. These results also confirmed the results of our earlier studies on the subcellular distribution of this mRNA by Northern blot analysis. Further studies were also performed to determine whether withdrawal of muscle cells from the cell cycle during differentiation to form myotubes alone was responsible for regulating translation of P-40 mRNA. The results of the subcellular distribution of this mRNA in proliferating myoblasts following inhibition of DNA synthesis by cytosine arabinoside have shown that translation of P-40 mRNA continued in absence of DNA synthesis. This observation suggests that an additional signal is necessary to block the translation of P-40 mRNA in myotubes. The relationship between the translation of P-40 mRNA and its stability was examined. Two different methods were used to determine the stability of mRNAs. The first approach was by determining the steady-state levels of this mRNA following inhibition of RNA synthesis by actinomycin D. In the second method, we have determined the amount of 3H-labeled P-40 mRNA during pulse and chase experiments. Both methods produced similar results. It was found that the stability of P-40 mRNA was not altered during differentiation of rat L6 cells. The results of pulse and chase studies have also shown that P-40 mRNA was synthesized in both myoblasts and myotubes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3350003 TI - Expression of a constitutive form of cytochrome P450 during rat-liver development and sexual maturation. AB - Cytochrome P450 cDNA clone designated pP450 IGC 1 has been previously isolated from a phenobarbital-induced rat liver cDNA library, characterized and proven to correspond to a constitutive cytochrome P450 sensitive to phenobarbital stimulation. IGC 1 pDNA, as well as a unique synthetic oligonucleotide probe, were used to investigate the mRNA levels at different developmental stages (fetal, male and female rats of various ages) in parallel with the study of the expression of the liver development and male phenotype markers: albumin, alpha fetoprotein and alpha 2u globulin mRNAs. Cytochrome P450 IGC 1 mRNA responsiveness to phenobarbital administration was studied in animals of both sexes at different developmental stages. P450 IGC 1 mRNA was not detectable in fetuses nor in male or female rat liver before sexual maturation, becoming elevated at 45 days age, increasing up to 3 months and reaching relatively higher levels in the female liver than in the male. The concentrations of P450 IGC 1 mRNA closely paralleled the increases in alpha 2u globulin mRNA in male liver, as analyzed by dot and Northern blot hybridization. However, P450 IGC 1 was markedly induced by phenobarbital already at 20 days age both in males and females while alpha 2u globulin mRNA was not inducible before sexual maturation. It is concluded that the expression of cytochrome P450 IGC 1 mRNA is associated with the sexual maturation being differently modulated in the male and in the female rat liver. This cytochrome P450 isoenzyme may play an important physiological role in sex differential steroid metabolism and susceptibility to cytotoxic and genotoxic agents. PMID- 3350004 TI - Circular dichroic spectra of elapid cardiotoxins. AB - Cardiotoxins isolated from elapid snake venoms constitute a chemically homogeneous family of molecules. Within this group several biologically different subclasses exist. We report a comparative analysis of the structure of 20 cardiotoxins using circular dichroism, immunological methods and secondary structure prediction. It is shown that cardiotoxins fall within two structural subclasses. Toxins of group I are characterized by (a) CD spectra having an intense positive band close to 192.5 nm and a negative trough at 225 nm with no positive band around 230 nm, (b) strong cross-reactivity with a polyclonal antiserum specific for Naja nigricollis toxin gamma and (c) a high tendency to form a reverse turn in the region of position 11. Toxins of group II are characterized by (a) CD spectra displaying a much weaker positive band at 192.5 nm, a negative band around 210 nm and a positive band at 230 nm, (b) little cross reactivity with the aforementioned antiserum and (c) a high reverse-turn potential at position 31. It is suggested that the observed differences result from differing curvatures in the antiparallel beta sheet which constitutes the main secondary structure of cardiotoxins. PMID- 3350005 TI - Purification, properties and complete amino acid sequence of the ferredoxin from a green alga, Chlamydomonas reinhardtii. AB - The ferredoxin was purified from the green alga, Chlamydomonas reinhardtii. The protein showed typical absorption and circular dichroism spectra of a [2Fe-2S] ferredoxin. When compared with spinach ferredoxin, the C. reinhardtii protein was less effective in the catalysis of NADP+ photoreduction, but its activity was higher in the light activation of C. reinhardtii malate dehydrogenase (NADP). The complete amino acid sequence was determined by automated Edman degradation of the whole protein and of peptides obtained by trypsin and chymotrypsin digestions and by CNBr cleavage. The protein consists of 94 residues, with Tyr at both NH2 and COOH termini. The positions of the four cysteines binding the two iron atoms are similar to those found in other [2Fe-2S] ferredoxins. The primary structure of C. reinhardtii ferredoxin showed a great homology (about 80%) with ferredoxins from two other green algae. PMID- 3350006 TI - Mechanism of glyceraldehyde-3-phosphate transfer from aldolase to glyceraldehyde 3-phosphate dehydrogenase. AB - The catalytic interaction of glyceraldehyde-3-phosphate dehydrogenase with glyceraldehyde 3-phosphate has been examined by transient-state kinetic methods. The results confirm previous reports that the apparent Km for oxidative phosphorylation of glyceraldehyde 3-phosphate decreases at least 50-fold when the substrate is generated in a coupled reaction system through the action of aldolase on fructose 1,6-bisphosphate, but lend no support to the proposal that glyceraldehyde 3-phosphate is directly transferred between the two enzymes without prior release to the reaction medium. A theoretical analysis is presented which shows that the kinetic behaviour of the coupled two-enzyme system is compatible in all respects tested with a free-diffusion mechanism for the transfer of glyceraldehyde 3-phosphate from the producing enzyme to the consuming one. PMID- 3350007 TI - Characterization of four tyrosine protein kinases from the particulate fraction of rat spleen. AB - Four distinct tyrosine protein kinases active on poly(Glu4,Tyr1) and angiotensin II, and operationally termed TPK-I, TPK-IIA, TPK-IIB and TPK-III have been resolved and partially purified from rat spleen particulate fraction by combining DEAE-Sepharose, heparin-Sepharose, phosphocellulose and polylysine-agarose chromatographies. Once partially purified all of them are free of Ser/Thr specific protein kinase activity as judged using casein, histones, protamine and the peptide Arg-Arg-Ala-Ser-Val-Ala as substrates. TPK-I (apparent molecular mass 64 kDa, by gel filtration) and TPK-IIA (54 kDa) share several properties, including substrate specificity and stimulation by heparin; the latter however is much more responsive to polylysine then the former (10- and 3-fold maximum stimulation, respectively). Conversely TPK-IIB (51 kDa) is markedly inhibited by heparin and it is also characterized by its unique substrate specificity: unlike the other three tyrosine protein kinases it by far prefers the tetrapeptide Glu Tyr-Ala-Ala over the decapeptide Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Arg-Arg-Gly and readily phosphorylates band-3 protein of red cell membrane. The unusual preference for Mg2+ over Mn2+ as activator and the capability to phosphorylate calmodulin distinguish TPK-III (61 kDa) from the other isoenzymes. Moreover TPK III is insensitive to heparin and polylysine and is inhibited by quercetin much more efficiently than the other enzymes (I50 = 10 microM). Upon incubation with [gamma-32P]ATP, TPK-I, TPK-IIA and TPK-III give rise to alkali-stable radiolabeled components of 61, 55 and 52 kDa respectively, as evaluated by PAGE/SDS. In every case such a radiolabeling takes place also in the presence of a large excess of phosphorylatable substrate (angiotensin II) while it is readily reversed by isotopic dilution with 10-fold excess unlabeled ATP, supporting the view that it represents an autophosphorylation process. No (auto)phosphorylation product(s) could be detected in TPK-IIB even if its amount, in terms of catalytic activity, was 10-fold higher than that of the others. PMID- 3350008 TI - Diversity of corrinoids in acetogenic bacteria. P-cresolylcobamide from Sporomusa ovata, 5-methoxy-6-methylbenzimidazolylcobamide from Clostridium formicoaceticum and vitamin B12 from Acetobacterium woodii. AB - The Co beta-cyanocobamides obtained by cyanide extractions from several acetogenic bacteria were structurally characterized by ultraviolet/visible spectra, proton-nuclear-magnetic-resonance spectra and fast-atom-bombardment mass spectra. p-Cresolycobamide was detected as a major corrinoid from Sporomusa ovata. This 'complete' corrinoid was isolated from an organism for the first time. Instead of the common Co alpha bases of the known and biologically active cobamides, p-cresolylcobamide contained a glycosidically bound cresolyl function that was unable to coordinate to the cobalt of the corrin ring. An additional, previously unknown corrinoid from natural sources, Co alpha-[alpha-(5-methoxy-6 methylbenzimidazolyl)]-Co beta-cyanocobamide, was isolated along with vitamin B12 from Clostridium formicoaceticum. Both homoacetogenic eubacteria were grown on methanol and contained high amounts of corrinoids (greater than 950 nmol/g cell dry mass). Less corrinoid was isolated from Acetobacterium woodii and characterized as vitamin B12. PMID- 3350009 TI - Control by pH of urea synthesis in isolated rat hepatocytes. AB - Control by pH of urea synthesis has been studied in isolated rat hepatocytes incubated with a physiological mixture of amino acids. Inhibition of urea synthesis by decreasing the pH of the medium was caused by diminished production of ammonia and not, as suggested in the literature, by inhibition of entry of ammonia into the ornithine cycle. The decrease by low pH of the rate of degradation of the added amino acids, that of alanine being quantitatively the most important, was accompanied by a decrease in their intracellular concentration. It is concluded that inhibited transport of amino acids across the plasma membrane of the hepatocyte is responsible, at least in part, for the fall in urea synthesis with decreasing pH. It is proposed that inhibition by low pH of other steps in the ureogenic pathway, distal to the production of ammonia, does not affect flux through the ornithine cycle per se, but rather contributes to the buffering of the intrahepatic concentration of ammonia. PMID- 3350010 TI - Substrate specificity, regiospecificity and stereospecificity of halogenation reactions catalyzed by non-heme-type bromoperoxidase of Corallina pilulifera. AB - Many organic compounds were found to be substrates for halogenation reactions catalyzed by the non-heme-type bromoperoxidase found in the red alga Corallina pilulifera. Anisole, 1-methoxynaphthalene and thiophene were converted to o and p bromoanisoles, 1-methoxy-4-bromonaphthalene and 2-bromothiophene respectively. Regiospecificity of the enzymatic bromination of anisole was tested and found to be the same as in the chemical reaction with NaOBr. The enzyme also acted on substituted alkenes such as styrene, cyclohexene, trans-cinnamic acid, trans cinnamyl alcohol and cis-propenylphosphonic acid, to give the respective bromohydrin compounds or decarboxylated bromo compound. These bromohydrin compounds were always mixtures of stereoisomers. In the light of the above findings together with the previous studies concerning the halogenation mechanism, the bromoperoxidase of C. pilulifera was considered to have no specific restriction site for these substrates. PMID- 3350011 TI - Low-molecular-mass surfactant protein type 1. The primary structure of a hydrophobic 8-kDa polypeptide with eight half-cystine residues. AB - The low-molecular-mass surfactant protein fraction, soluble in chloroform/methanol, contains at least two separate polypeptide chains. The 8-kDa form (type I) was isolated, [14C]carboxymethylated after reduction, and submitted to structural analysis. Its highly hydrophobic nature complicated purification, proteolytic cleavages, and sequence analysis. Acid hydrolysis in 6 M HCl for 7 days was necessary for release of branched-chain residues in full yield. Pepsin was the only enzyme found to cleave the surfactant protein and was used to complement peptide generation by chemical cleavage with CNBr. The primary structure deduced consists of 79 residues with 8 half-cystine residues, and a total of 39% branched-chain hydrophobic residues. However, 11 residues are charged at physiological pH, and all properties of the primary structure are not entirely outstanding in relation to those of other proteins. Hydrophobic segments, coupled with a presumably tight folding from the presence of disulfide bridges, probably explain the unusual properties and the solubility in organic solvents. PMID- 3350012 TI - Mitochondrial aldehyde dehydrogenase from horse liver. Correlations of the same species variants for both the cytosolic and the mitochondrial forms of an enzyme. AB - The primary structure of the mitochondrial form of horse liver aldehyde dehydrogenase has been determined, utilizing peptide analyses and homology with other enzyme forms. The subunit exhibits N-terminal heterogeneity in size similar to that for the corresponding human mitochondrial protein, the longest form having 500 residues. Catalase was identified as a contaminant of the preparations. All four pairs within a set of aldehyde dehydrogenases can now be compared, including the same two species variants (horse and human) for both the cytosolic and mitochondrial enzyme, revealing characteristic differences although Cys-302 and other segments of presumed functional importance are unchanged. The cytosolic and mitochondrial enzymes are clearly different (172 exchanges in the horse pair; 160 exchanges in the human pair) and the mitochondrial forms are more conserved (28 exchanges of 500 residues) than the cytosolic ones (43 exchanges). Distributions of the residue substitutions also differ between the two enzyme types. These results suggest a comparatively distant separation of the cytosolic and mitochondrial enzymes into forms with separate functional constraints that are more strict on the mitochondrial than the cytosolic enzyme. Unexpectedly, positions with residues unique to one of the four enzymes are about twice as common in both of the horse proteins than in either of the human proteins. This difference may reflect a general pattern for human/non-human proteins, showing that not only functional properties of the protein, but also other factors, such as generation time (longer in man than in horse), are important for enzyme divergence. PMID- 3350013 TI - Deoxycytidylate hydroxymethylase gene of bacteriophage T4. Nucleotide sequence determination and over-expression of the gene. AB - We describe two approaches to cloning and over-expressing gene 42 of bacteriophage T4, which encodes the early enzyme deoxycytidylate hydroxymethylase. In Bochum a library of sonicated fragments of wild-type phage DNA cloned into M13mp18 was screened with clones known to contain parts of gene 42. Two overlapping fragments, each of which contained one end of the gene, were cleaved at a HincII site and joined, to give a fragment containing the entire gene. In Corvallis a 1.8-kb fragment of cytosine-substituted DNA, believed to contain the entire gene, was cloned into pUC18 and shown to express the enzyme at low level. The cloned fragment bore an amber mutation in gene 42. From the DNA sequence of gene 42, the cloned gene was converted to the wild-type allele by site-directed mutagenesis. Both gene-42-containing fragments were cloned into the pT7 expression system and found to be substantially overexpressed. dCMP hydroxymethylase purified from one of the over-expressing strains had a turnover number similar to that of the enzyme isolated earlier from infected cells. In addition, the N-terminal 20 amino acid residues matched precisely the sequence predicted from the gene sequence. The amino acid sequence of gp42 bears considerable homology with that of thymidylate synthase of either host or T4 origin. The gene 42 nucleotide sequences of bacteriophages T2 and T6 were determined and found to code for amino acid sequences nearly identical to that of T4 gp42. PMID- 3350015 TI - The transmembrane electrochemical gradient of Na+ as driving force for methanol oxidation in Methanosarcina barkeri. AB - A sodium ion gradient (inside low) across the cytoplasmic membrane of Methanosarcina barkeri was required for methanogenesis from methanol. This could be concluded from the following results. (a) Inhibition of the Na+/H+ antiporter by K+ or amiloride led to an inhibition of methanogenesis from methanol. (b) Upon addition of the sodium ionophore monensin the Na+ gradient was abolished and at the same time methanogenesis from methanol was inhibited. (c) Methanogenesis was impaired when the Na+ gradient had the opposite orientation (inside high). All these inhibitory effects were not observed when H2 was present in addition to methanol indicating that the oxidation of methanol to CO2 was driven by a sodium motive force. In accordance with this, a methanol-dependent influx of Na+ and a corresponding decrease of the membrane potential could be observed, when the Na+/H+ antiporter was inhibited by amiloride. This influx was indicative of the presence of a Na+ transport system which was functional when the oxidation of methanol had to be driven, but was not functional when H2 was present for reduction of methanol to methane. PMID- 3350014 TI - On the importance of the support material for bioorganic synthesis. Influence of water partition between solvent, enzyme and solid support in water-poor reaction media. AB - alpha-Chymotrypsin was adsorbed on solid support materials and the catalytic activity of the preparations in organic solvents was studied. The activity was highly dependent on the nature of the support material and on the amount of water present in the reaction mixture. There appears to be competition for the water in the system between the enzyme, the support material and the solvent. The support materials were characterized by measuring their ability to absorb water from water-saturated diisopropyl ether. For the quotient: (amount of water on the support)/(amount of water in the solvent) in the model system the term aquaphilicity was proposed. The activity of adsorbed chymotrypsin in diisopropyl ether decreased with increasing aquaphilicity of the support material. The same trend was observed when the activity of horse liver alcohol dehydrogenase adsorbed on different supports was measured in diisopropyl ether. PMID- 3350016 TI - Ionic-strength-dependent substrate inhibition of the lysis of Micrococcus luteus by hen egg-white lysozyme. AB - The kinetics of lysis of Micrococcus luteus by hen egg-white lysozyme in dilute buffer media is characterized by pronounced substrate inhibition. This effect occurs within the complete pH range where lysozyme activity is detectable. The electrostatic potential of the negatively charged cell-wall proteoglycan increases with decreasing ionic strength, resulting in an enhanced affinity between proteoglycan and lysozyme and probably favouring multipoint substrate attachment. For the lysozyme-catalyzed hydrolysis of cell-wall proteoglycan three plausible mechanisms of substrate inhibition can be postulated. Two out of the three models fit our experimental data, the simplest of the two providing the most rigorous information on the kinetic parameters Km, V and Ki. Three graphical methods consistent with the chosen model were applied for preliminary parameter estimation and the constants obtained were compared to those from nonlinear least squares analysis. If substrate inhibition is neglected it is shown that serious bias is imposed upon the parameters. PMID- 3350017 TI - tRNA-mediated labelling of proteins with biotin. A nonradioactive method for the detection of cell-free translation products. AB - We have developed a new method for the rapid and sensitive detection of cell-free translation products. Biotinylated lysine is incorporated into newly synthesized proteins by means of lysyl-tRNA that is modified in the epsilon-position. After electrophoresis in a dodecyl sulfate gel and blotting onto nitrocellulose, the translation products can be identified by probing with streptavidin and biotinylated alkaline phosphatase, followed by incubation with a chromogenic enzyme substrate. The non-radioactive labelling by biotin approaches in its sensitivity that obtained by radioactive amino acids. The products are absolutely stable and can be rapidly identified. The new method has been tested with different mRNAs in the cell-free translation systems of wheat germ and reticulocytes. Neither the interaction of secretory proteins with the signal recognition particle nor the in vitro translocation across the endoplasmic reticulum membrane or core glycosylation of nascent polypeptides are prevented by the incorporation of biotinylated lysine residues. The results indicate that both the ribosome and the endoplasmic reticulum membrane permit the passage of polypeptides carrying bulky groups attached to the amino acids (by atomic models it was estimated that the size of the side chain of lysine changes from approximately equal to 0.8 nm to approximately equal to 2 nm after modification. PMID- 3350018 TI - The final step in methane formation. Investigations with highly purified methyl CoM reductase (component C) from Methanobacterium thermoautotrophicum (strain Marburg). AB - Methyl-coenzyme M reductase (= component C) from Methanobacterium thermoautotrophicum (strain Marburg) was highly purified via anaerobic fast protein liquid chromatography on columns of Mono Q and Superose 6. The enzyme was found to catalyze the reduction of methylcoenzyme M (CH3-S-CoM) with N-7 mercaptoheptanoylthreonine phosphate (H-S-HTP = component B) to CH4. The mixed disulfide of H-S-CoM and H-S-HTP (CoM-S-S-HTP) was the other major product formed. The specific activity was up to 75 nmol min-1 mg protein-1. In the presence of dithiothreitol and of reduced corrinoids or titanium(III) citrate the specific rate of CH3-S-CoM reduction to CH4 with H-S-HTP increased to 0.5-2 mumol min-1 mg protein-1. Under these conditions the CoM-S-S-HTP formed from CH3-S-CoM and H-S-HTP was completely reduced to H-S-CoM and H-S-HTP. Methyl-CoM reductase was specific for H-S-HTP as electron donor. Neither N-6-mercaptohexanoylthreonine phosphate (H-S-HxoTP) nor N-8-mercaptooctanoylthreonine phosphate (H-S-OcoTP) nor any other thiol compound could substitute for H-S-HTP. On the contrary, H-S-HxoTP (apparent Ki = 0.1 microM) and H-S-OcoTP (apparent Ki = 15 microM) were found to be effective inhibitors of methyl-CoM reductase, inhibition being non-competitive with CH3-S-CoM and competitive with H-S-HTP. PMID- 3350019 TI - Complete amino acid sequences of the ribosomal proteins L25, L29 and L31 from the archaebacterium Halobacterium marismortui. AB - Ribosomal proteins were extracted from 50S ribosomal subunits of the archaebacterium Halobacterium marismortui by decreasing the concentration of Mg2+ and K+, and the proteins were separated and purified by ion-exchange column chromatography on DEAE-cellulose. Ten proteins were purified to homogeneity and three of these proteins were subjected to sequence analysis. The complete amino acid sequences of the ribosomal proteins L25, L29 and L31 were established by analyses of the peptides obtained by enzymatic digestion with trypsin, Staphylococcus aureus protease, chymotrypsin and lysylendopeptidase. Proteins L25, L29 and L31 consist of 84, 115 and 95 amino acid residues with the molecular masses of 9472 Da, 12293 Da and 10418 Da respectively. A comparison of their sequences with those of other large-ribosomal-subunit proteins from other organisms revealed that protein L25 from H. marismortui is homologous to protein L23 from Escherichia coli (34.6%), Bacillus stearothermophilus (41.8%), and tobacco chloroplasts (16.3%) as well as to protein L25 from yeast (38.0%). Proteins L29 and L31 do not appear to be homologous to any other ribosomal proteins whose structures are so far known. PMID- 3350021 TI - Free sphingoid bases in normal murine tissues. AB - Free sphingoid bases, which have been considered not to occur naturally, were detected in murine tissues by derivatization with o-phthalaldehyde and the use of high-performance liquid chromatography. The concentrations were 10-30 pmol/mg tissue. The lung contained the largest amounts of sphingoid bases. In the molecular species of sphingoid bases, the most abundant was C18-sphingenine followed by C18-sphinganine, 4-hydroxysphinganine and C20-sphingenine, in that order. The central nervous tissues contained relatively high amounts of C20 sphingenine and there was a high concentration of 4-hydroxysphinganine in the kidney. In addition, galactosylsphingenine was detected simultaneously in the spinal cord and sciatic nerve. Sphingoid bases were purified from normal murine lungs using lipid-extraction, cation-exchange and silicic acid column chromatographies, alkaline saponification and preparative thin-layer chromatography. In the purified sphingoid bases, erythro-C18-sphingenine and erythro-C18-sphinganine were identified using thin-layer chromatography, high performance liquid chromatography and fast-atom-bombardment mass spectrometry. Free sphingoid bases occurring in normal tissues may be metabolic intermediates required for the synthesis or be products of degradation of the sphingolipids and function to regulate cellular metabolism. PMID- 3350020 TI - Fluorescence-quenching-resolved spectroscopy of proteins. AB - A new procedure is described for using fluorescence-quenching data of tryptophan residues in proteins to resolve their fluorescence emission spectra. In this concept the Stern-Volmer quenching plot is determined at each particular emission wavelength and iterative non-linear least-squares fitting procedure allowed to resolve the steady-state emission spectra into components. The resolved components, attributed to each of tryptophan residue, can be characterized by different accessibility to the quencher. The ability to resolve fluorescence emission spectra can be improved by using different kinds of efficient quenchers, which can selectively quench the emission of exposed or both exposed and buried fluorophores. The method was used to decompose emission fluorescence spectra in two-tryptophan-containing proteins; horse liver dehydrogenase, sperm whale apomyoglobin and metalloprotease from Staphylococcus aureus. The resolved spectra of alcohol dehydrogenase and metalloprotease are in excellent agreement with those previously obtained by single-photon counting or phase methods. The method presented here is technically simple and does not require expensive instrumentation. PMID- 3350022 TI - Rapid activation of human platelets by low concentrations of low-density lipoprotein via phosphatidylinositol cycle. AB - The interaction of low-density lipoprotein (LDL) with the human platelet was investigated with regard to saturable high-affinity binding, shape change, cytosolic free Ca2+ concentration, phosphatidylinositol (PtdIns) turnover, and thromboxane B2 biosynthesis. The experiments show that LDL, at a concentration approximately 100 times lower than in plasma, causes platelet activation concomitantly with stimulation of the PtdIns cycle and thromboxane B2 formation, similarly to other activators of platelets. The effects of LDL were inhibited by high-density lipoprotein. The results suggest that activation of platelets by low concentrations of LDL may play a role in pathophysiological conditions and that platelet can serve as a model for studying the influence of LDL on various target cells. PMID- 3350023 TI - Structural and transcriptional characterization of the external spacer of a ribosomal RNA nuclear gene from a higher plant. AB - A lambda recombinant phage, carrying a radish rDNA fragment spanning the complete external spacer and its borders, has been isolated and characterized by sequencing. The fragment is 2911 bp long and includes 486 bp of the 3' end of the 25S rRNA sequence, 2349 bp of spacer and the first 76 bp of the 5' end of the 18S rRNA sequence. The spacer can be divided into three regions: two unique domains flanking a 830-bp region of repeated sequences. Seven repeats ranging from 80 to 103 bp can be recognized. They are separated by short arrays of 12-21 adenylic residues. Each repeat slightly differs from the others by single-nucleotide changes or short deletions. Examination of single-nucleotide changes common to two units suggests that a duplication arose during the evolution of this sequence. The repeated region was subcloned and used as a probe to demonstrate that it is highly species-specific: in stringent conditions it does not cross hybridize with the spacer of ribosomal genes from closely related species such as Brassica. Transcription products, starting or finishing within the spacer sequence, were mapped by northern blotting, primer extension and S1 mapping. Two major precursors were identified starting respectively at positions 2095 and 2280. The region surrounding the start at 2095 presents extensive homology with an analogous region in maize, rye, mung bean, Xenopus and tse-tse fly. However, longer transcripts can be detected. Several 3' ends downstream of the 25S terminus were also observed. Taken together these results indicate that rDNA transcription and pre-rRNA processing in plants are more complex than anticipated from previous studies. PMID- 3350025 TI - Significance of pre-infarction angina for occurrence of post-infarction angina. AB - We evaluated the factors determining the occurrence of post-infarction angina in 41 patients who had intra-coronary thrombolysis within 6 h of the onset of acute myocardial infarction. Pre-infarction angina was considered to be present if it occurred more than one week before acute myocardial infarction. Post-infarction angina was defined as typical chest pain occurring within 10 days following the infarction. Collateral flow to the infarct zone was determined to be present if any portion of the infarct-related epicardial artery or side branches was visualized. In cases of successful thrombolysis, the prevalence of post infarction angina was not significantly influenced by pre-infarction angina and the extent of collateral circulation. However, in patients without recanalization, pre-infarction angina and collateral blood flow supply to the area at risk caused a high prevalence of angina after infarction. It is concluded that pre-infarction angina indicative of myocardial ischemia is associated with post-infarction angina especially in patients with conventional therapy, because the jeopardized myocardium is salvaged substantially by collateral circulation with a limited flow reserve. PMID- 3350024 TI - Biosynthesis and turnover of a 34-kDa protein growth factor in human cytotrophoblasts. AB - Recently we isolated a new protein growth factor of 34 kDa from synctial membranes of human placenta. In its polypeptide molecular mass, antigenic structure, receptor binding specificity and partial amino acid sequence, it is unlike several known growth factors, hormones and other proteins. Here we report studies on its biosynthesis and turnover in cultured cytotrophoblasts from term human placenta. Expression of the 34-kDa protein in these cells was studied by immunoprecipitation and Western blot analyses using a highly specific antibody. The experiments have produced the following results. a) Immunostaining and Western blot analyses have demonstrated the presence of immunoreactive 34-kDa protein in isolated cytotrophoblasts. The protein is present in both freshly isolated cells and in cells that have fused in culture to form multinuclear syncytiotrophoblasts. b) Trophoblastic biosynthesis of the protein has been demonstrated by in vitro translation of cellular mRNA and by metabolic labelling experiments with intact cells. c) Pulse-chase experiments show that biosynthesis of the protein does not involve any detectable precursors of higher or lower molecular mass. d) Studies on turnover indicate that the synthesized protein is unusually stable with a half-life of 50-70 h. PMID- 3350026 TI - Normal diastolic filling patterns of the left ventricle. AB - Pulsed Doppler measurements on both sides of the mitral valve and M-mode left ventricular echocardiograms were performed in 215 healthy subjects, 120 males and 95 females, between one and 65 years old, in order to evaluate normal diastolic filling patterns of the left ventricle. The relation between the maximum blood velocity during early passive filling (E wave) and during atrial contraction (A wave) was computed from the Doppler spectra obtained proximal and distal to the mitral valve, resulting in the EA ratio. The influence on the EA ratio of age, gender, body surface area, blood pressure, heart rate, PR interval, respiration, wall thickness and basal wall mass of the left ventricle was investigated. The study showed that the EA ratio measured proximal to the mitral valve (in the left atrium) was significantly smaller than the EA ratio measured distal (in the left ventricle) and that the only prominent relations with the EA ratio were those with age and heart rate. The EA ratio declines with age: proximal to the mitral valve from approximately (medians) 2.5 to 1 and distal to it from 3.5 to 1.5. All other physiological variables are weakly related or unrelated to the EA ratio in this group of healthy subjects. PMID- 3350027 TI - Echocardiographic assessment of atrial tumour size and endogeneously generated contrast images. An experimental study. AB - Experimental models, in vitro and in vivo, were designed to simulate the motion of an atrioventricular valve leaflet and an atrial tumour. Cross-sectional echocardiography was used to investigate any changes in apparent tumour size related to its motion. Both parts of the study suggest that endogenous contrast, due to surfaces of different acoustic densities generated around the rapidly moving tumour, contributes to the echographic pattern of the tumour. Thus, during diastole, the echo-mass cloud is greater than the real size of the tumour. The echocardiographic and actual size of the tumour may be identical only in ventricular systole when the blood flow around the atrial tumour is greatly decreased. PMID- 3350028 TI - Unruptured aneurysm of the sinus of Valsalva presenting with ventricular tachycardia. AB - We report a case of a large unruptured aneurysm of the right sinus of Valsalva which caused severe right ventricular outflow tract obstruction and presented dramatically with a life threatening ventricular tachycardia. Despite severe aortic incompetence prior to surgery it was possible to resect the aneurysm and repair the aortic root without resort to aortic valve replacement and thus return the anatomy to normal. PMID- 3350029 TI - Strut-fracture of a Bjork-Shiley tilting disc valve diagnosed by echocardiography -a case report. AB - A 40-year-old man with Bjork-Shiley valves implanted in the aortic and mitral positions nine months previously presented with central chest pain. Shortly after admission he developed clinical features consistent with left ventricular failure. Fracture of the mitral prosthesis was diagnosed by echocardiography. At emergency operation the outlet strut of the mitral valve was found to be fractured and the disc was in the left ventricle. The patient survived valve re placement and is in good health four years later. PMID- 3350030 TI - Retrograde catheterization of left ventricle through mechanical aortic prostheses. PMID- 3350032 TI - Integrated reporting of quality and length of life--a statistician's perspective. AB - The reporting of trials has been dominated by a concentration on single measures of response, such as survival or extent of side-effects, perhaps selected as giving an impressive P value for treatment comparisons. Relevant questions about trade-offs are seldom answered or even envisaged in the trial design. Cardiovascular trials should provide evidence on quality of life after myocardial infarction or during antihypertensive therapy. Examples from oncology are used to illustrate how the robustness of treatment recommendation can be explored through a grid of quality adjustments, ranging from complete intolerance of side-effects to absolute acceptance of them. Treatment recommendations may need to be specific to patients unless they are independent of the system of quality adjustment used. PMID- 3350031 TI - The systolic hypertension in the elderly pilot program: methodological issues. AB - The Systolic Hypertension in the Elderly Program (SHEP) Pilot Study was conducted to determine the feasibility of conducting a long-term placebo-controlled randomized clinical trial in elderly subjects. Enrolled in the study were 551 men and women between the ages of 60 and 90 years with isolated systolic hypertension (SBP greater than or equal to 160 mmHg and DBP less than 90 mmHg). The study showed that it is possible to recruit old and very old subjects into a clinical trial; the elderly are good compliers (drugs and follow-up visits), with some decline after the age of 80; control of blood pressure was accomplished in the large majority of patients; evaluation of side effects represents a potential problem as varied complaints increase with age thus creating difficulties in distinguishing those attributed to the study drug; and finally, cause-specific mortality is probably preferable to all-cause mortality as an end-point in prevention trials of antihypertensive regimens. PMID- 3350033 TI - Persistent sternum synchondroses on bone scintigraphy. AB - This report describes the case history of two patients who showed a hyperactive midsternal area on bone scintigraphy due to a persistent sternal synchondrosis. Whereas this anatomical variant is diagnosed infrequently, midsternal hotspots can sometimes be related to arthrotic degeneration of these extra joint spaces. In the differential diagnosis of midsternal hotspots on bone scintigraphy, persistent sternum synchondroses should be considered. PMID- 3350034 TI - The biodistribution and pharmacokinetics of meta-iodobenzylguanidine in childhood neuroblastoma. AB - MIBG is generating considerable interest for the treatment of neuroblastoma. This study has investigated the biological variation in handling of the compound in children with neuroblastoma. The biodistribution of the compound has been characterised in children undergoing tracer administrations of 123I and 131I mIBG. Estimates of hepatic and whole body radiation dose delivery have been made. The results indicate substantial interpatient variation in hepatic dose delivery. This organ may be critical in some patients undergoing targeted radiotherapy with mIBG. PMID- 3350035 TI - Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody. AB - Current nuclear medicine techniques for the localization of inflammatory processes are based on injection of 111In labelled autologous granulocytes which need to be isolated and radiolabelled in vitro before reinjection. A new technique is presented here that obviates the need for cell isolation by the direct intravenous injection of a granulocyte specific 123I labelled monoclonal antibody. In this publication the basic parameters of the antibody granulocyte interaction are described. Antibody binding does not inhibit vital functions of the granulocytes, such as chemotaxis and superoxide generation. Scatchard analysis of binding data reveals an apparent affinity of the antibody for granulocytes of 6.8 X 10(9) l/mol and approximately 7.1 X 10(4) binding sites per cell. Due to the high specificity of the antibody, the only expected interference is from CEA producing tumors. PMID- 3350036 TI - A comparison of iodine and indium labelled anti CEA intact antibody, F(ab)2 and Fab fragments by imaging tumour xenografts. AB - An intact anti CEA monoclonal antibody (C198) and its F(ab)2 and Fab fragments have been radiolabelled with 131I and 111In and their biodistributions and tumour imaging capabilities examined in mice with human tumour xenografts. 131I labelled F(ab)2 and Fab fragments showed improved tumour visualization compared with intact antibody, principally because of the more rapid whole body elimination of the radiolabel. Studies using 111In labelled fragments demonstrated that a major proportion (greater than 60%) of the administered radioactivity was retained in the kidneys and this was detrimental to tumour imaging in the mouse xenograft model. The present study emphasizes the importance of selecting the most appropriate combination of antibody preparation and radiolabel, and that the choice of radionuclide is influenced by both its physical and subsequent pharmacological characteristics. PMID- 3350037 TI - The half-lives of serum immunoglobulins in adult mice. AB - We determined the half-lives of several sets of murine monoclonal antibodies spanning all immunoglobulin isotypes in the serum. The antibodies in each set possess the same V region. With this approach, the differences in half-life observed between the different isotypes are independent of the V region carried by the monoclonal antibodies and therefore must relate to each other in the same way as the half-lives of each class of serum immunoglobulins. The half-life of a monoclonal antibody of the gamma 2a isotype is identical to the average half-life of serum IgG2a as previously determined (6-8 days; P. Vieira and K. Rajewsky, Eur. J. Immunol. 1986. 16:871). Therefore, the half-lives determined with monoclonal antibodies possessing the same V region represent the half-life of the serum immunoglobulins. In this way we calculated the half-life of IgM as 2 days, IgG3 and IgG1 as 6-8 days, IgG2b has a half-life of 4-6 days. IgE has a half-life of 12 h. A polymeric form of IgA was found to be eliminated from the serum with a half-life of 17-22 h. PMID- 3350038 TI - Effects of isosorbide dinitrate and diltiazem on Ca2+ flux and contraction in artery. AB - We studied the effects of isosorbide dinitrate and diltiazem on histamine stimulated 45Ca fluxes and contractions of isolated porcine coronary artery. Isosorbide dinitrate was slightly more potent as an inhibitor of intracellular compared to extracellular calcium-dependent contraction. Isosorbide dinitrate inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction over similar concentration ranges. Isosorbide dinitrate partially inhibited histamine-stimulated calcium influx, but this effect was significant only at high concentration and correlated weakly with inhibition of contraction that was dependent on extracellular calcium. Diltiazem more potently inhibited extracellular vs. intracellular calcium-dependent contraction. Diltiazem partially inhibited histamine-stimulated calcium efflux and intracellular calcium dependent contraction to similar extents (55-60%) and produced similar concentration-response relationships for inhibition of histamine-stimulated calcium influx and extracellular calcium-dependent contraction. The data suggest that alterations of cellular calcium metabolism are major mechanisms of vascular smooth muscle relaxation by isosorbide dinitrate and diltiazem, but that the specific alterations differ for the two drugs. Isosorbide dinitrate may inhibit contraction primarily by enhancing intracellular calcium sequestration, but possibly also by inhibiting agonist-stimulated calcium influx at high isosorbide dinitrate concentrations. Diltiazem primarily inhibits stimulated calcium influx, but may also inhibit intracellular calcium release. PMID- 3350039 TI - The binding of [3H]telenzepine to muscarinic acetylcholine receptors in calf forebrain. AB - Telenzepine binds to calf brain muscarinic receptors with a selectivity for M1 receptors that is comparable to that exhibited by pirenzepine. Telenzepine has a 10-fold higher affinity than pirenzepine at these receptors and is equipotent with atropine. Because of its potency, selectivity and hydrophilicity, [3H]telenzepine is an excellent radioligand for binding to and monitoring M1 receptor binding sites. The kinetics of [3H]telenzepine binding are extremely slow, even at 37 degrees C. PMID- 3350041 TI - Characterization of high-affinity binding sites for the antitussive [3H]noscapine in guinea pig brain tissue. AB - We have characterized the binding of the antitussive alkaloid [3H]L-alpha noscapine ([3H]noscapine) to guinea pig brain. Binding of [3H]noscapine to brain homogenate is stereospecific, saturable, reversible, heat-sensitive and manifests high affinity (Kd = 7 nM). Binding sites are present in all major brain areas, with the thalamus exhibiting the highest density. Subcellular localization studies showed an enrichment of binding sites in the synaptosomal fraction. Some structurally related compounds with antitussive properties (narceine, hydrastine, narcotoline and papaverine) were potent competitors, while other antitussives did not inhibit [3H]noscapine binding. Various ligands that bind to known neurotransmitter receptors failed to displace [3H]noscapine binding or had IC50 values in the micromolar range. It was concluded that the noscapine binding sites are different from those previously described for antitussives such as codeine and other opiates, or dextromethorphan. PMID- 3350040 TI - An antiarrhythmic effect of adenosine during myocardial ischaemia and reperfusion. AB - Adenosine (10 micrograms kg-1 min-1, infused into the lumen of the left ventricle) and dipyridamole (0.25 mg kg-1 intravenously, a dose that potentiated markedly the fall in arterial pressure in response to bolus doses of adenosine) each reduced the number of extrasystoles which occurred during the first 30 minutes following coronary artery occlusion in anaesthetised greyhound dogs (from 786 +/- 115 in control dogs to 156 +/- 44 in those treated with adenosine and to 388 +/- 167 with dipyridamole). Intracoronary adenosine (1 microgram kg-1 min-1, infused into the ischaemic area) however appeared to increase the number of extrasystoles to 1230 +/- 214. Left ventricular infusion of adenosine reduced the incidence of ventricular fibrillation (from 88 to 43%) when the ischaemic myocardium was perfused at the end of a 40 min occlusion period. In the dose used in this study (10 micrograms kg-1 min-1) adenosine caused a sustained fall in blood pressure but did not alter blood gases. In control dogs the levels of purine derivatives in blood draining the myocardium rendered ischaemic by coronary artery occlusion (local coronary venous samples) increased gradually during the ischaemic period (from 9 +/- 3 microM pre-occlusion to 25 +/- 7 microM post-occlusion). Dipyridamole increased the resting plasma concentration of purines prior to occlusion by approximately 90%; these remained raised for the occlusion period. These results support the suggestion that adenosine may act as a locally produced endogenous antiarrhythmic agent. PMID- 3350042 TI - Endothelium-dependent relaxation in estrogen-treated spontaneously hypertensive rats. AB - Female spontaneously hypertensive rats (SHR) were injected subcutaneously with mestranol twice a week for 12 weeks. Isolated segments of thoracic aorta were then used to generate relaxation response curves to acetylcholine or ATP after precontraction with phenylephrine. Estrogen treatment attenuated the development of hypertension. Further, augmented endothelium-dependent relaxation to acetylcholine was seen in the estrogen-treated SHR. There was no difference, however, in the relaxation produced by ATP. Since the relaxation of both acetylcholine and ATP is endothelium-dependent, these findings suggest that different mechanisms may be involved in the relaxation produced by acetylcholine and ATP. PMID- 3350043 TI - Ketanserin antagonises the anorectic effect of DL-fenfluramine in the rat. AB - To determine the role played by 5-HT2 receptors in the anorectic action of DL fenfluramine, the ability of the selective 5-HT2 receptor antagonist ketanserin to block the reduction in food intake produced by this drug was investigated in non-deprived rats. Ketanserin (1 and 2.5 mg/kg i.p.) produced a dose-dependent antagonism of the anorectic effect of DL-fenfluramine (3 mg/kg i.p.). Prazosin (1 mg/kg i.p.) did not antagonise this effect. It is concluded that the anorectic actions of DL-fenfluramine are mediated via 5-HT2 receptors. PMID- 3350044 TI - The effect of epithelium removal on non-adrenergic, non-cholinergic inhibitory responses in the isolated central airways of the cat and guinea pig. AB - Epithelium removal from the feline or the indomethacin-treated guinea pig trachea had no effect on tissue sensitivity or responsiveness to the contractile actions of pharmacological agonists or electrical field stimulation. In the feline hilar bronchus, epithelium removal had no effect on tissue sensitivity or responsiveness to acetylcholine or electrical field stimulation but increased bronchial sensitivity to serotonin without affecting responsiveness. Non adrenergic non-cholinergic (NANC) relaxation responses elicited by electrical field stimulation in airway preparations from either species were unaffected by epithelium removal. These results suggest that the epithelium does not modulate contractile responses in the feline trachea but may modulate the actions of specific contractile agonists in the feline hilar bronchus. Further, NANC relaxation responses appear to occur independently of the airway epithelium. PMID- 3350045 TI - The influence of oxaprotiline enantiomers given repeatedly on the behavioural effects of d-amphetamine and dopamine injected into the nucleus accumbens. AB - The effects of (+)- and (-)-oxaprotiline, given repeatedly (10 mg/kg p.o., twice daily, 14 days), on the behavioural action of d-amphetamine and dopamine injected bilaterally into the nucleus accumbens were studied in rats. Repeated but not acute treatment with (+)- or (-)-oxaprotiline enhanced the d-amphetamine-induced locomotor hyperactivity. Both enantiomers, given repeatedly but not acutely, attenuated the inhibition of exploration activity induced by dopamine and potentiated the stimulating effect of dopamine as assessed in the open field test. The results indicate that, like other antidepressants studied previously, both oxaprotilines increase the responsiveness of the dopamine mesolimbic system (nucleus accumbens) of the rat. PMID- 3350046 TI - Evidence for a direct peripheral effect of clonidine on the norepinephrine release in vivo in pithed rats. AB - To study the in vivo peripheral effects of clonidine on sympathetic neuronal function we measured, after different doses of clonidine, plasma norepinephrine (NE) and blood pressure (BP) responses during electric stimulation of sympathetic outflow in pithed male Sprague-Dawley rats. In this preparation, clonidine produced dose-dependent inhibition of the sympathetic stimulation-induced pressor and plasma NE responses. The dose of clonidine inhibiting the NE response by 50% (ID50) was 14.2 +/- 0.3 micrograms/kg i.v., while ID50 for the diastolic pressor response was 22.0 +/- 0.2 micrograms/kg i.v. Since clonidine did not alter the relationship between NE released into the plasma and the pressor responses, the entire effect of clonidine in decreasing the pressor response to sympathetic stimulation may be attributed to its presynaptic alpha 2-adrenoceptor-mediated inhibition of NE release. PMID- 3350048 TI - Activity-dependent differences between rat fast and slow neuromuscular systems. AB - Activity-dependent pharmacologic differences between the fast tibialis anterior and slow soleus neuromuscular systems of the rat were studied. The tibialis anterior was more sensitive than the soleus to d-tubocurarine tetanic fade (50 Hz), as determined from recordings of compound muscle action potentials. Pre treatment with physostigmine prevented curare-induced tetanic fade in the tibialis anterior, but not the soleus. Additionally, when contractile tension was 80% blocked by d-tubocurarine, the tibialis anterior was more responsive than the soleus to the decurarizing action of tetanic stimulation (25, 50 and 100 Hz). These results disclose that activity-dependent pharmacologic differences exist between neuromuscular systems. Further, they indicate that the tibialis anterior and the soleus differ in their processes of transmitter release. It is speculated that differences in nerve terminal Ca2+ account for the observed pharmacologic differences between the tibialis anterior and soleus. PMID- 3350049 TI - Methoctramine reveals heterogeneity of M2 muscarinic receptors in longitudinal ileal smooth muscle membranes. AB - Direct binding studies on longitudinal ileal and atrial muscarinic receptors revealed that most of the ileal or atrial selective antagonists identified in functional studies did not differentiate between these muscarinic receptors in direct binding studies. Methoctramine, an atrial selective muscarinic receptor antagonist in functional studies was, however, able to partially discriminate between these two receptors in our binding studies. Furthermore the binding data obtained using this compound indicated that longitudinal ileal muscarinic receptors were heterogeneous. The predominant population of ileal muscarinic receptors displayed a similar pharmacology to the cardiac type M2 muscarinic receptor. The minor population of muscarinic receptors identified in binding studies displayed a similar pharmacology to the ileal muscarinic receptor identified in functional studies and were pharmacologically similar to the exocrine gland type M2 muscarinic receptor. PMID- 3350047 TI - Indolealkylamine analogs share 5-HT2 binding characteristics with phenylalkylamine hallucinogens. AB - Twenty-one indolealkylamines, some of which are known to be psychoactive in man, were examined for their binding interactions with rat brain cortical 5-HT2 receptors labeled with the antagonist radioligand [3H]ketanserin in order to develop structure-activity relationships for binding at these sites. Features investigated included aromatic, alpha-methyl and terminal amine substituents. 4 Methoxy and 5-methoxy substitution impart a higher affinity than 6- or 7-methoxy substitution; a 7-hydroxyl group essentially abolishes affinity whereas a 7 methyl or 7-bromo group enhances affinity. alpha-Methylation has little effect on affinity and, in the one case examined, the S(+) isomer of alpha-methyltryptamine was essentially equipotent with its racemate and twice as potent as its R(-) enantiomer. Terminal amine methylation results in a small but progressive decrease in affinity in the order: primary amine greater than dimethylamine greater than diethylamine. Similarities were noted between these structural requirements for binding and those of the phenalkylamines. Selected compounds (5 methoxytryptamine, N,N-dimethyltryptamine, 5-methoxy-N,N-diethyltryptamine and 5 methoxy-N,N-dimethyltryptamine) were further examined by two-site analysis of displacement studies for [3H]ketanserin specific binding. Hill coefficients were significantly less than unity and computer-assisted analysis indicated that a two site model better fit the data than a one-site model. In displacement studies using the putative agonist radioligand [3H]DOB to label 5-HT2 receptors affinities were 10-100-fold higher than those using [3H]ketanserin. These results are also consistent with earlier findings using psychoactive phenalkylamines in competition studies for radiolabelled 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350050 TI - Ryanodine in mammalian heart ventricular muscle: indication for the induction of calcium leakage from the sarcoplasmic reticulum. AB - Ryanodine at nanomolar concentrations suppressed the earlier of two contraction components which can be produced in guinea-pig papillary muscles, in the presence of noradrenaline (3 microM) at a low contraction frequency (0.2 Hz). However, test contractions elicited shortly after a steady state contraction showed an unimpaired early contraction component. This component declined with increases in the interval preceding the test contraction at a rate depending on the ryanodine concentration (the apparent first-order rate constant 0.07 s-1 of the spontaneous decline was doubled by about 0.2 nM and was increased to 1.3 s-1 by 10 nM ryanodine). The effect of ryanodine resembled that of a potassium-induced depolarization with the exception that it was not antagonized by an increase in the extracellular magnesium concentration. It is concluded that ryanodine enhances the leakage of stored calcium in mammalian heart muscle, probably by a direct influence on the calcium release channels of the junctional sarcoplasmic reticulum of the heart muscle cell. PMID- 3350051 TI - The neurotensin analog xenopsin excites nigral dopamine neurons. AB - The electrophysiological effects of neurotensin (NT), its analog xenopsin, and the fragment NT-(1-8) on the activity of dopaminergic neurons in rat substantia nigra slices were compared. Xenopsin and NT produced a concentration-dependent increase in the firing rate. The mean firing rate was increased by 58.5% with xenopsin (0.1 microM) and 49.1% with NT (0.1 microM). NT-(1-8) was inactive at this concentration. Dopamine (100 microM) inhibited firing in these neurons by 54.7%. These data provide evidence that xenopsin mimics the physiological effects of NT. PMID- 3350052 TI - Atropine- and endothelium-dependent relaxation. PMID- 3350053 TI - Nicotinic acetylcholine receptors in the rat stomach: II. Alterations after vagotomy. AB - Nicotinic and muscarinic acetylcholine receptors were studied in the stomach of vagotomized rats, with ligand binding techniques, and with the concomitant measurement of choline acetyltransferase (ChAT). The maximum binding capacity (Bmax) of the high affinity sites of (-)-[3H]nicotine binding was significantly increased in all the regions of the stomach of subdiaphragmatically vagotomized animals while the values for the low affinity sites remained the same as those in sham-operated animals. On the other hand, [3H]quinuclidinyl benzilate binding to the stomach was unchanged after vagotomy. ChAT activity was significantly reduced in the vagotomized rats. These results suggest that surgical vagal denervation causes an increase in the density of nicotinic acetylcholine receptors presumably located on the parasympathetic ganglion cells. There is also a reduction of ChAT activity, probably due to a degenerative loss of preganglionic cholinergic neurons. Preganglionic denervation (decentralization) has little influence on the muscarinic receptors of postsynaptic effector organs. PMID- 3350055 TI - Effect of isomazole on the responsiveness to calcium of the contractile elements in skinned cardiac muscle fibres of various species. AB - We report here that the new cardiotonic agent isomazole increases the Ca2+ responsiveness of skinned myocardial fibres from different species. Isomazole (0.01-1 mM) increased the half-maximal, Ca2+-activated force development in atrial fibres from humans and in ventricular fibres from pigs, monkeys, guinea pigs and rats in a concentration-dependent manner. The maximal force development was also increased in fibres from all species except pig. Isomazole shifted force calcium curves to the left and enhanced maximal force as demonstrated for guinea pig and human fibres, indicating increases in both calcium sensitivity and maximum force-generating capability of the contractile apparatus. In guinea-pig tissue, the concentration dependence for the activation of skinned fibres was similar to that for the positive inotropic effect in papillary muscle. These results suggest a direct effect of isomazole on contractile proteins, but the degree to which this effect contributes to the overall positive inotropic action of isomazole remains to be determined. PMID- 3350054 TI - Thromboxane A2 and the development of hypertension in spontaneously hypertensive rats. AB - Osmotic minipumps containing OKY-046 (15-20 mg/kg per day), to inhibit thromboxane (TX) A2 synthase, were implanted into 43-day-old SHR and age-matched Wistar-Kyoto rats (WKY) to study the role of TXA2 in the development of hypertension in SHR. Inhibition of TXA2 synthase with OKY-046 did not affect urine volume, sodium excretion, potassium excretion, food and water intake or body weight in either WKY or SHR during the two weeks of study. In the first week systolic blood pressure (SBP) was significantly lower in SHR receiving OKY-046 in comparison to SHR which received no OKY-046 (127 +/- 3 vs. 110 +/- 4 mm Hg, P less than 0.01). OKY-046 did not affect SBP in WKY. By the second week SBP in SHR and WKY receiving OKY-046 did not differ from their respective controls despite an 85% reduction in serum immunoreactive TXB2 (iTXB2; the stable hydrolysis product of TXA2) and a 45% reduction in urinary iTXB2 excretion. These results support a possible role for TXA2 in the developmental stage of hypertension in SHR and other factors in the sustained elevation of blood pressure. PMID- 3350056 TI - Central and peripheral hypotensive effects of the optical isomers of nicardipine, a dihydropyridine calcium channel antagonist, in rats. AB - Central and peripheral hypotensive effects of (+)- and (-)-nicardipine (1-10 micrograms/kg i.v. or i.c.v.) were investigated in normotensive and SH rats. The results suggest that a stereoselectivity exists for the peripheral and central hypotensive effects of the nicardipine isomers. (+)-Nicardipine was shown to be 3 8 times as potent as the (-) isomer in reducing blood pressure in all the experiments. PMID- 3350057 TI - A 5-HT receptor in the central nervous system, positively coupled with adenylate cyclase, is antagonized by ICS 205 930. PMID- 3350058 TI - Cardiac versus vascular effects of a new dihydropyridine derivative, CV-4093. In vitro comparison with other calcium antagonists. AB - The effects of CV-4093, a new dihydropyridine derivative, on isolated cardiovascular tissues were compared with those of several dihydropyridine and non-dihydropyridine calcium antagonists. CV-4093 effectively inhibited the contractions induced in canine femoral arteries by high [K+]0 and Bay K 8644, but incompletely relaxed those induced by norepinephrine. CV-4093, 10(-6) M, abolished the electrically induced slow action potentials in guinea-pig papillary muscles partially depolarized by 25 mM K+ solution and attenuated those induced by isoproterenol, histamine and Bay K 8644. The rank order of potency of dihydropyridine and non-dihydropyridine calcium antagonists in canine femoral arteries and veins precontracted with 120 mM [K+]0 was as follows: nisoldipine greater than nicardipine greater than or equal to nifedipine greater than or equal to CV-4093 greater than verapamil greater than or equal to diltiazem. Nisoldipine was the most potent and CV-4093 was the least potent among these drugs in terms of negative inotropic effect in normally polarized papillary muscles and negative chronotropic effect in right atria of guinea pigs. The rank order of potency for these cardiodepressant actions was nisoldipine greater than or equal to nifedipine greater than nicardipine greater than verapamil greater than diltiazem greater than or equal to CV-4093. The duration of action potential in guinea-pig papillary muscles was shortened by nisoldipine and nifedipine, unchanged by nicardipine and CV-4093 and was slightly prolonged by verapamil and diltiazem. These results suggest that CV-4093 is a calcium antagonist with a highly selective vascular effect and little cardiodepressant action, and could be of value for the treatment of hypertension. PMID- 3350059 TI - Pertussis toxin inhibits antinociception produced by intrathecal injection of morphine, noradrenaline and baclofen. AB - The effect of intrathecal pretreatment with pertussis toxin on the spinal antinociceptive effect of morphine, noradrenaline and L-baclofen was examined in rats implanted with chronic indwelling cannulas. Pretreatment with 0.25-0.75 micrograms pertussis toxin for 2-7 days inhibited antinociception produced by intrathecal injection of all three agents in the tail flick test. Inhibition also occurred in the hot plate test, but was less pronounced than in the tail flick test. When doses of the three agents giving similar levels of antinociception were compared in a single group, the degree of inhibition of antinociception was comparable. Inhibition of the effect of noradrenaline was observed up to 14 days following pretreatment. The sensitivity of spinal antinociception to pertussis toxin suggests involvement of a guanine nucleotide regulatory protein in spinal actions of morphine, noradrenaline and L-baclofen. There is support in the literature for the additional involvement of adenylate cyclase in the action of morphine and noradrenaline but not of baclofen. PMID- 3350060 TI - Nicotinic acetylcholine receptors in the rat stomach: I. (-)-[3H]nicotine binding. AB - The nicotinic acetylcholine receptors in the rat stomach were characterized by means of a radioligand binding assay with (-)-[3H]nicotine as ligand. Saturation binding studies on the gastric fundus membranes revealed the presence of two binding sites with dissociation constant (KD) values of 3.1 and 289 nM, and maximum binding capacity (Bmax) values of 3.6 and 76 fmol/mg protein, respectively. The Bmax of the high affinity binding site was greatest in the cardia, followed by fundal mucosa, fundal muscle, and, finally antrum. The IC50 values of cholinergic drugs to inhibit (-)-[3H]nicotine binding in fundus membranes were as follows: (-)nicotine, 0.12 nM; cytosine, 9.3 nM; acetylcholine, 17.7 nM; carbachol, 700 nM; hexamethonium, 2270 nM. The IC50 values of alpha bungarotoxin, d-tubocurarine and atropine were greater than 100 microM. The muscarinic acetylcholine receptors were also characterized with [3H]quinuclidinyl benzilate and the choline acetyltransferase activity was measured. These results suggest that nicotinic acetylcholine receptors as well as muscarinic acetylcholine receptors are present in the rat stomach and that the regional distribution of these receptors is uneven. PMID- 3350061 TI - Effects of the slow calcium-channel blocker verapamil on phosphatic metabolism of crystalline lens. AB - The effects of calcium-channel blockade on phosphate metabolism in the rabbit lens ex vivo was studied using phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy. Rates-of-change of the intralenticular pH and the following phosphatic metabolites in the lens were determined: ATP, ADP, inorganic orthophosphate, sugar phosphates, nucleoside diphosphosugars, phosphodiesters, dinucleotides, and an uncharacterized resonance peak at 6 delta in the 31P spectrum. Incubation in 20, 200 or 2000 micrograms/ml verapamil led to the same qualitative changes in the lens's metabolic profile at each different concentration; only the rates of metabolite change were altered significantly by verapamil concentration. Compared with the control, the entire orthophosphate resonance band increased relative to the signals of ATP, and the alpha glycerophosphate and nucleoside monophosphate resonances increased in relation to inorganic orthophosphate, and these two resonance groups shifted relative to each other so that they coalesced, indicating that the two groups of signals arose from compounds in relatively different pH compartments. In addition to altering metabolic rates, verapamil reduced the intralenticular pH of the sugar phosphate and inorganic orthophosphate pools with respect to those containing the nucleoside monophosphates; the pH-change difference was about one order of magnitude smaller for the mononucleotide pool. Despite the metabolic alterations and changes in pH during verapamil incubation, lens clarity was unchanged. PMID- 3350062 TI - Substitution of porphyropsin for rhodopsin in mouse retina. AB - Weanling, male albino mice were placed on a vitamin A-free diet for three months to deplete their vitamin A stores. The vitamin A-deficient mice were injected intraperitoneally with all-trans 3-dehydroretinol. 3-dehydroretinol was rapidly incorporated into the liver as a fatty acid ester. The chromophore of visual pigment increased gradually and reached a normal level 13 days after the injection. 3-Dehydroretinal accounted for 95% of the total chromophore in the retina. The high proportion of 3-dehydroretinal was observed also in the long term experiment which was continued for six weeks with the injection of 3 dehydroretinol once a week. When the animal was injected with a mixture of 3 dehydroretinol and retinol, the ratio of dehydroretinal/retinal in the retina was far lower than the ratio of dehydroretinol/retinol in the liver. These results indicate that 3-dehydroretinol is not converted to retinol in mouse and is used less efficiently than retinol for the chromophore of visual pigment. The synthesis of visual pigment was observed even when the animal was kept in complete darkness after the injection of all-trans 3-dehydroretinol. This fact indicates that light is not required for the production of 11-cis chromophore of visual pigment. PMID- 3350063 TI - Signs of early damage in glaucomatous monkey eyes: low spatial frequency losses in the pattern ERG and VEP. AB - Experimental glaucoma was created in one eye of three cynomolgus monkeys by argon laser application to the mid-trabecular meshwork. Simultaneous pattern electroretinograms (PERG) and pattern visual evoked potentials (PVEP) were measured in both control and glaucoma eyes to spatial frequencies of 0.5, 1.25, 2.5, and 3.5 cpd which were counterphase modulated at 6 Hz. The transient flash electroretinogram was also measured. While normal flash electroretinograms were recorded in all eyes both before and after the unilateral production of elevated intraocular pressure (IOP), reductions in PERG and PVEP amplitude were seen in the eyes with glaucoma as early as two weeks following a sustained increase of IOP, despite the absence of cupping of the optic nervehead judged by ophthalmoscopic examination and analysis of photograph by two observers. Optic nervehead abnormalities occurred subsequently. In glaucomatous monkey eyes, the earliest PERG and PVEP changes were most evident with lower spatial frequencies of stimulation. Our data suggest that the optimal stimulus parameters for the detection of early glaucoma are low spatial frequency patterns presented at a rapid rate of temporal modulation. PMID- 3350064 TI - Visual function and rhodopsin levels in humans with vitamin A deficiency. AB - Details of rod and cone dysfunction in vitamin A deficiency have been studied in two subjects with primary biliary cirrhosis and one with Crohn's disease, all of whom presented with symptoms of night blindness. Visual function in the mid peripheral retina was monitored with two-color adaptometry and rhodopsin levels were measured by fundus reflectometry. Initially all three subjects had no measurable rod function and delayed cone adaptation. In one case the dark-adapted cone threshold was also elevated. Oral supplementation with vitamin A restored visual function to normal within 8 days in all subjects. During supplementation, cone function was restored more rapidly than that of rods, though the pattern of recovery was similar for each receptor type. Final thresholds improved first, though the rates at which they were reached were abnormally slow. As recovery continued, adaptation kinetics returned to normal. When rod adaptation was delayed, the regeneration of rhodopsin was also abnormally slow. When rod final threshold was 2 log units higher than normal, rhodopsin regeneration was incomplete, reaching about 70% of the normal level. The initial stages of visual dysfunction during onset of vitamin A deficiency were studied in one subject, and were found to mirror the pattern seen during recovery: rod adaptation was initially slower than normal, but reached completion. Cone adaptation remained normal until rod function was almost absent. PMID- 3350065 TI - Definition and comparison of the phosphorylation sites of the A and B chains of bovine alpha-crystallin. AB - The major phosphorylation sites of bovine alpha-crystallin Ser122 in the A chain, Ser59 and Ser43 and/or Ser45 in the B chain have been previously characterized. Further analysis of total alpha-crystallin, isolated from the cortex of calf lenses incubated in the presence of [32P]orthophosphate, demonstrated the presence of additional phosphorylation sites in both chains. At least three additional phosphorylation sites were found in the A chain and at least one in the B chain. These additional sites accounted for approximately 25% of the radioactivity incorporated in the protein. Two general sequences were found in most phosphorylation sites of both chains of alpha-crystallin: (Arg/Lys)-(X)-Pro Ser and Ser-(X)-Ser-Leu-Ser. In spite of the 57% homology in the sequences of the A and B chains, the phosphorylation sites are located, in the A polypeptide, at the C-terminal third and in the B polypeptide, at the N-terminal third. The alignment of the regions containing the phosphorylation sites of both chains (C terminal third of the A and N-terminal third of the B chain) revealed an unexpected similarity in the relative positions of the sites in each chain. PMID- 3350066 TI - Influence of the activity of glutathione reductase on the response of cultured lens epithelial cells from young and old rabbits to hydrogen peroxide. AB - Our previous studies on cultured rabbit lens epithelial cells from 4-day-old rabbits showed that the glutathione redox cycle plays an important role in detoxifying H2O2, a potentially damaging oxidant present in the aqueous humor. Here we report the effect of donor age and cell density on the ability of cultured rabbit lens epithelial cells to detoxify H2O2. Lens epithelial cells (8 x 10(5] from a 4-day-old and an 8-year-old rabbit were cultured for 3 hr in minimal essential medium (MEM) or in MEM containing 0.01-0.1 mM H2O2 maintained with glucose oxidase. We determined the effect of H2O2 on the level of reduced glutathione (GSH), hexose monophosphate shunt activity, cell growth, and morphology. For growth studies, cells were exposed to the desired concentration of H2O2 for 3 hr and then cultured in MEM plus 10% rabbit serum for 7 days and counted. Young and old untreated cells contained high levels (30-40 nmol/8 x 10(5) cells) of GSH. Cells from 4-day-old rabbits tolerated 0.03 mM H2O2 with no effect on GSH and a minimal decrease in subsequent cell growth. However, in the older cells, GSH and growth were substantially diminished following treatment with 0.03 mM H2O2. Cells plated out at high density (8 x 10(5] were more tolerant of 0.03 mM H2O2 than cells plated out at low density (5 x 10(4]. Maximum shunt activity in the younger cells exposed to H2O2 was twice that of the older cells and occurred at a higher level of H2O2 (0.04 compared with 0.03 mM). Enzyme activities in untreated young and old cells were comparable for hexokinase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase. However, glutathione reductase activity was 50% lower in the cells from the 8-year-old rabbit. The toxicity of H2O2 to cultured lens epithelial cells was directly related to donor age and inversely related to cell density. The damage in the older lens epithelial cells at 0.03 mM H2O2 was apparently due, in part, to a diminished response of the glutathione redox cycle to oxidative challenge. PMID- 3350067 TI - Synergism between environmental lighting and taurine depletion in causing photoreceptor cell degeneration. AB - Experiments were conducted to examine the possible interaction between retinal taurine depletion and environmental lighting in causing photoreceptor cell degeneration. Albino rats were raised from birth in either dim (2 lx) or relatively bright (300 lx) cyclic light. Beginning at weaning, half the animals from both light environments were taurine-depleted by treating them for 10 weeks with guanidinoethyl sulfonate as a 1% solution in their drinking water. The remaining animals were given ordinary tap-water and served as controls. In the 2 lx light environment, taurine depletion caused a decrease in electroretinogram (ERG) a- and b-wave amplitude of 36 and 46%, respectively; however, no photoreceptor cells were lost in this group. Tap-water controls kept in the 300 lx light environment had a 59- and 43% decrease in ERG a- and b-wave amplitude, respectively, and a 21% reduction in the number of photoreceptor cells. In contrast to the other groups, animals that were taurine-depleted in the 300 lx environment showed a marked retinal degeneration. ERG a- and b-wave amplitude was decreased by 94- and 89% respectively and there was a 62% loss of photoreceptor cells. The greatest cell loss occurred in the central superior region of the retina, in which the outer nuclear layer was typically reduced to one to two rows of nuclei. The results of a two-way analysis of variance applied to the data indicated that the effects of taurine depletion on the retina were greater in the 300 lx as compared with the 2 lx environment in terms of loss of photoreceptor cells and reduction in log ERG a- and b-wave amplitude. These findings demonstrate a synergism between environmental lighting and taurine depletion in causing photoreceptor cell degeneration. PMID- 3350068 TI - The gecko visual pigment: the chromophore dark exchange reaction. AB - This study confirms the occurrence of a dark-exchange reaction in the extracted 521-pigment of the Tokay gecko (G. gekko). The present study involved the exchange, in the dark, of the natural 11-cis-chromophore by the 9-cis-10-F retinal analog. This analog is able to combine with the 521-opsin to regenerate a photopigment at 492 nm. In addition to this shift in absorbance from 521 to 492 nm, the analog photopigment has a photosensitivity some 2.4% that of the native 521-system in the chloride-sufficient state. These two properties of the regenerated analog pigment have simplified the demonstration of a dark exchange of chromophores. At 15 degrees C the 9-cis-10-F-analog replaces the 11-cis chromophore by at least 30% (density-wise) in about 15 hr. This exchange occurs with the system in the chloride-deficient state. The presence of chloride during the period in the dark significantly reduces the magnitude of the exchange. Apparently, the protein has a more open structure at the chromophoric binding site, allowing this interchange of chromophores. The addition of chloride induces a conformational change at this site, 'burying' the Schiff base and reducing the exchange reaction. The biological implication of this mobile property of the gecko opsin is that it is similar to the behavior of the cone pigment iodopsin but is unlike that of rhodopsins. This supports the idea that the gecko visual cells, despite their appearance as rods, are phylogenetically related to ancestral photopic receptors. PMID- 3350069 TI - Raman spectroscopic evaluation of aging and long-wave UV exposure in the guinea pig lens: a possible model for human aging. AB - The laser Raman optical dissection technique makes it possible to study individual points of minute volumes (2 X 10(-3) microliter) in the intact living lens in vitro. This technique was used to measure the sulfhydryl and disulfide content of 21 distinct points along the visual axis of the guinea-pig lens after aging and long-wave ultraviolet exposure (9-month duration in vivo). To facilitate comparison between different lenses, data was compiled as the intensity ratio of sulfhydryl (2580 cm-1) to a protein reference signal (2731 cm 1) or disulfide (508 cm-1) to phenylalanine (622 cm-1). These 21 ratios for each experiment were plotted as a function of the distance of the point from the nuclear center of the lens to give a visual axis profile. From these profiles we have found that the loss of sulfhydryl can be accelerated in the guinea-pig lens by in vivo ultraviolet exposure (353 nm peak from an incoherent source) for nine months. There is also a subsequent uniform increase in the disulfide content across the visual axis after UV exposure suggesting a direct sulfhydryl to disulfide conversion in the guinea-pig lens. PMID- 3350071 TI - Lipid contamination of disks depends on rod outer-segment purity. PMID- 3350070 TI - Age-related changes in fibre differentiation of rat lens epithelial cells in vitro. AB - Epithelial cells in explants from rat lenses differentiate into fibre cells when cultured with retina conditioned medium (RCM). This differentiation is characterised by cell elongation, the accumulation of alpha-crystallin and the onset of synthesis of the fibre specific beta- and gamma-crystallins. To determine the effect of donor age on the synthesis of beta- and gamma-crystallins in response to culture with RCM, we explanted lens epithelia from 3-, 10- and 21 day-old rats. Explants were trimmed to obtain a population of central epithelial cells and at the end of the culture period crystallin content was measured by ELISA methods and expressed per unit DNA. Explants from 3- and 10-day-old rats showed significant increases in the levels of beta-crystallin/DNA within four days after the addition of RCM. The synthesis of beta-crystallin in explants from 21-day-old rats was delayed until after day 4 of culture, but rose quickly to reach the same levels at 10 days as the explants from younger lenses. The ability of lens epithelia to synthesise gamma-crystallin in response to RCM showed a dramatic decline as the age of the donor rat increased. After 10 days of culture, explants from 10-day-old rats contained only 12% of the amount of gamma crystallin accumulated by explants from 3-day-old rats. Explants from 21-day-old rats accumulated no significant gamma-crystallin until day 10 of culture, and at this time the amount was significantly less than that accumulated by explants from younger rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350072 TI - Choroidal blood flow measured in the dog eye in vivo and in vitro by local hydrogen clearance polarography: validation of a technique and response to raised intraocular pressure. AB - Local choroidal flow has been measured using hydrogen (H2) clearance polarography in dog eyes in vivo and in vitro. The accuracy and reproducibility of the method was checked in the eye in vitro by demonstrating a linear relationship between flow measurements obtained by an absolute method and those obtained by the H2 clearance technique. The H2 electrode was placed through a scleral window and its current response to a bolus injection of H2-saturated saline into a proximal artery was measured. The clearance of H2 from the choroidal circulation in vitro was monoexponential and the reproducibility of the measurements at the same site and in the same eye was good. In vivo the technique was used to measure alterations in local choroidal blood flow produced by acute changes of intraocular pressure. A linear relationship between perfusion pressure and choroidal blood flow was obtained. H2 clearance polarography is shown to be an accurate and reproducible method for determining choroidal flow, with the advantage that localized repeated measurements of flow can be made. PMID- 3350073 TI - Detection of extracellular matrix molecules synthesized in vitro by monkey and human retinal pigment epithelium: influence of donor age and multiple passages. AB - The retinal pigment epithelium of various species, including man, can synthesize extracellular matrix components in vitro. We studied extracellular matrix molecule production by human, rhesus and cynomolgus monkey pigment epithelium in vitro, using a panel of specific antibodies to collagen types I-V, fibronectin, laminin, the basement membrane heparan sulfate proteoglycan, human alpha elastin, glial fibrillary acidic protein (GFAP), and Factor VIII in a modified indirect immunofluorescence reaction. Results were similar between human and both monkey species in early passage cultures with respect to the positive detection of collagen types I, III, IV, V laminin, basement membrane proteoglycan, and fibronectin. The fluorescence was strongest in the center of confluent monolayers and was absent in border or isolated cells. Collagen type II, elastin, GFAP, or Factor VIII were not detected. Based on these findings, human and monkey pigment epithelium in vitro should be useful for the study of the synthesis, deposition and supramolecular interactions of a variety of extracellular matrix molecules. PMID- 3350074 TI - Effects of alpha-chymotrypsin on the outflow routes for aqueous humor. AB - The anterior chamber was perfused with alpha-chymotrypsin, 50 micrograms ml-1, in mock aqueous humor in cynomolgus monkeys. The enzyme caused a marked rise in outflow facility and had clear effects on the structure of the outflow routes for aqueous humor. The intertrabecular spaces in the iridocorneal chamber angle were wider than normal, the openings in the uveal and corneoscleral meshwork appeared enlarged, there was ballooning of the juxtacanalicular region and the inner wall of Schlemm's canal into the canal and also splitting of the inner wall of the canal. The trabecular cells appeared relaxed with most of the cell processes retracted, some broken. There were discontinuities in the cell membrane and blebs. Parts of the trabecular beams were denuded. Two days after the enzyme treatment the facility was in the normal range, no splits in the inner wall of Schlemm's canal we observed but many of the other changes in structure remained. The number of invaginations in the inner wall of Schlemm's canal was markedly reduced after 2-18 days. A second and third perfusion with alpha-chymotrypsin caused a rise in outflow facility similar to the first. Some morphological changes remained 163 days after enzyme treatment. Pilocarpine a few days after alpha-chymotrypsin treatment caused a marked increase in outflow facility. The results suggest that alpha-chymotrypsin affects the glycoproteins of the cell membrane and as a result causes disorganization of the cytoskeleton, loss of loose adhesions and breaks of cell processes. The rapid recovery of the resistance to outflow was probably due to healing of the splits in the inner wall of Schlemm's canal; a marked reduction in the number of cells with invaginations suggests that in addition there may have been a reduction in the number of transcellular pores in the inner wall of Schlemm's canal. PMID- 3350076 TI - Variation in the relative abundance of gamma-crystallin gene transcripts during development and ageing. AB - The transcripts of gamma-crystallin mRNA were examined during adulthood. The mRNA transcripts were detected by Northern blot technique. Although the total RNA per lens measured remains constant during adulthood, the mRNA transcript size was observed to decline with ageing, specifically for the gamma-crystallin and not for alpha- and beta-crystallins. We could show that the relative amount of mRNA transcripts detected with the four probes decreased with ageing, with gamma 1 and gamma 2 transcripts being found at a higher level than the gamma 3 and gamma 4 transcripts. PMID- 3350075 TI - Evolutionary and functional relationships between the basic and acidic beta crystallins. AB - beta-Crystallins are complex oligomers composed of many related subunits. In order to understand their interactions we have built molecular models of several bovine beta-crystallins, based on their sequence similarity to the well-defined gamma-II crystallin structure, using interactive computer graphics techniques. Their common origin with gamma-crystallin is displayed in both the retention of four-fold sequence repeats of critical residues involved with stabilizing a folded beta-hairpin and the conservation of core-filling hydrophobic side-chains. The beta-crystallins have been built as bilobal molecules with each domain composed of two 'Greek key' motifs which associate about an approximate two-fold axis to form beta-sheets. The beta-crystallin sequences have previously been shown to comprise two families, the basic and acidic subunits, which have extensions of sequence. The three-dimensional models show how the two families appear to stabilize the folded beta-hairpin in the N- and C-terminal domains in ways which suggest that they have diverged from a common ancestor in different ways. Acidic beta-crystallins, like gamma-crystallins, have a regular array of charges on their N-terminal domain which has been interrupted in basic beta crystallins by hydrophobic residues which may be related to the presence of a C terminal extension. beta-Crystallins are more highly charged than gamma crystallins although their charge density is higher in certain regions of the N terminal domain, particularly in beta B1-crystallin. beta-crystallins also differ from gamma-crystallins in the virtual absence of core-filling sulphydryl groups whereas they have numerous sulphur-containing side-chains together with tryptophan and histidine rings protruding from the globular domains, particularly in the acidic subunits. The burial of these residues in subunit contacts is consistent with their spectroscopic and electrostatic properties. Protein subunit aggregation commonly occurs through hydrophobic interaction or beta-sheet extension. Analysis of the subunit surfaces has identified an N-terminal hydrophobic region common to beta B1 and beta B2 whereas a C-terminal hydrophobic loop region is common to beta B1 and beta A1 and may be correlated with their association properties. It is suggested that the polar C-terminal domain of beta B2 contributes towards the solubility of higher aggregates by interactions involving beta-sheet structure. PMID- 3350077 TI - Pharmacological characterization of human ciliary muscle adrenoceptors in vitro. AB - The in vitro pharmacological characteristics of adrenoceptors of the human ciliary muscle were investigated. Tissue was obtained from 30 eyes used previously for corneal transplantations which had been enucleated 6-24 hr after death. Experiments were performed within 2 days of enucleation. Strips of the meridional and circular portion of the ciliary muscle were attached to a tension gauge in an organ bath and the effect of drugs added to the perfusion medium was monitored isometrically. The muscle was precontracted with physostigmine (10(-5) M) and acetylcholine (10(-5) M). The non-selective beta adrenoceptor agonist isoproterenol (10(-6)-10(-3) M) caused a dose-related relaxation of the ciliary muscle, an effect which was completely inhibited by the non-selective beta adrenoceptor antagonist timolol (10(-5) M), while the beta 1 adrenoceptor antagonist betaxolol (10(-5) M) had no effect. The beta 2 adrenoceptor agonist salbutamol (10(-6)-10(-3) M) produced a dose-related relaxation of the ciliary muscle, an effect which was completely blocked by the beta 2 adrenoceptor antagonist L1 32-468 (10(-5) M). The non-selective alpha adrenoceptor agonist noradrenaline (10(-6)-10(-3) M) also caused a dose-related relaxation of the ciliary muscle. The non-selective alpha adrenoceptor antagonists phentolamine (10(-5) M) and thymoxamine (10(-5) M) and the alpha 1 adrenoceptor antagonist prazosin (10(-5) M) partially blocked the response to noradrenaline, while the alpha 2 adrenoceptor antagonist idazoxan (10(-5) M) and timolol (10(-5) M) had no effect. The alpha 1 adrenoceptor agonist phenylephrine (5 X 10(-6)-5 X 10(-3) M) caused a dose-dependent relaxation in five out of 12 isoproterenol-sensitive muscle strips. Further, it was not possible to block the phenylephrine-induced relaxation with thymoxamine (10(-5) M). The alpha 2 adrenoceptor agonist clonidine (10(-6)-10(-3) M) had no effect. No qualitative difference between drug effects on the meridional and circular ciliary muscles was observed. We conclude from these data that beta 2, and most probably alpha 1, adrenoceptors are present on both the meridional and circular portions of the ciliary muscle of the human eye. PMID- 3350078 TI - Comparative studies of collagens in normal and keratoconus corneas. AB - In this paper we present strong evidence that the aberrations in keratoconus corneas are not directly related to alterations in collagen composition and distribution. This conclusion is based on comparative studies of collagen types I, III, IV, V and the recently described collagen types VI and VII in keratoconus and normal corneas. The data are derived from biochemical analysis of collagen fractions sequentially extracted with pepsin and sodium-dodecylsulphate, from amino acid analysis of hydrolysates of entire corneal tissues as well as from immunoblotting of the extracted collagens with specific antibodies. These antibodies were also used to examine the distribution of the collagens in immunofluorescence experiments on corneal sections. The yields of the collagen extractions were demonstrated to be age dependent but were not altered in keratoconus samples. Apart from one case associated with osteogenesis imperfecta type I, comparative studies of keratoconus and normal corneas showed no differences in collagen composition of the extracts. This was confirmed by amino acid analysis of tissue-hydrolysates. The distributions of collagen types I, III, IV, V, VI and VII in corneal sections were in general unchanged in keratoconus corneas, the only differences being in scar tissues observed in the Bowman layer of some keratoconus samples. PMID- 3350079 TI - Immunohistochemical investigation of topographic localization of phenobarbital and methamphetamine in the rat retina. AB - The topographic localization of methamphetamine and phenobarbital in the rat retina was studied. It is interesting that the secondary and primary ganglionic cells were stained predominantly only in the case of methamphetamine while in phenobarbital these were not stained. The staining patterns of the inner plexiform layer (strong reaction in phenobarbital and weak reaction in methamphetamine), outer nuclear layer (weak reaction in phenobarbital and strong reaction in methamphetamine) and choroid (very strong reaction in phenobarbital and no reaction in methamphetamine) also showed some differences. PMID- 3350080 TI - The energy status of lenses from human donor eyes. PMID- 3350081 TI - Alterations of dendritic branching and spine densities of hippocampal CA3 pyramidal neurons induced by operant conditioning in the phase of brain growth spurt. AB - An operant conditioning study was carried out on Wistar rat pups of brain-growth spurt age to assess the plasticity of apical dendritic branching and the numerical spine densities of CA3 pyramidal neurons of the hippocampus. In rapid Golgi-stained material we studied the effects of operant conditioning commencing at 16 days of age and terminating on the 23rd day of age. The data of the learning group (L) were compared with those of the sham experimental control group (E) and of the control group reared under standard conditions (S). The results revealed a significant (ANOVA F test) increase in the number of branching points of the dendrites of the learning group compared with the other groups. The grand averages of spine densities also showed an overall increase in the learning group over the sham-experimental and standard groups. Segmental comparisons revealed a more interesting observation that significant changes in the spine densities of the learning and sham-experimental groups occurred in some segments of dendrites but not in all. A few segments showed moderate spine decreases also, compared with the control group. The spine differences of segments were mainly in the stalked types. Excrescences which are spines on which mossy fibers are known to synapse increased in both learning and sham-experimental groups, but not significantly (ANOVA). The dendritic branching and spines of nonmossy inputs of certain dendritic segments significantly increased after the learning experience in the hippocampus of the growing brain. PMID- 3350082 TI - Loss of neurons in the red nucleus after spinal cord transection. AB - Red nucleus neurons, particularly those of the caudal one-half of the nucleus, die or severely atrophy following complete spinal cord transection at T9. The size of residual horseradish peroxidase-labeled cells was smaller at 10 and 15 weeks, but those survivors which could be labeled at 25 weeks were normal in size. Hematoxylin and eosin-stained sections of the red nucleus at 52 weeks postoperative showed loss of cells from all size groups. PMID- 3350083 TI - Morphology of dendrite bundles in the cervical spinal cord of the rat: a light microscopic study. AB - Histological staining techniques and Golgi-Cox impregnation revealed three discrete dendrite bundles in the ventral horn of the rat cervical spinal cord. A midline dendrite bundle (MDB) traversed the ventromedial gray matter (C3-6), a central dendrite bundle (CDB) coursed the medial aspect of the ventral horn (C3 5), and a lateral dendrite bundle (LDB) traveled in the ventrolateral gray matter (C2-4). At the light microscopic level, the three dendrite bundles were composed of longitudinally oriented intertwined dendrites that coursed in close apposition among motoneuron perikarya, neuroglia, and capillaries. A gradient of packing density of dendrites in the bundles existed, the MDB displaying the greatest packing density and the LDB forming the most loosely interwoven dendritic plexus. Dendrites contributing to the bundles originated from several different motoneuron pools. Smaller transverse dendrite bundles radiated from the longitudinal dendrite bundles at right angles and appeared to interconnect the MDB, CDB, and LDB. Transverse dendrite bundles also exited the MDB and LDB to course into the anterior and lateral funiculi, respectively. The presence of dendrite bundles among fields of motoneurons suggests that dendrite bundles may provide an anatomical substrate for the synchronization of neuronal activity for coordination of muscle groups involved in particular movements. Dendrite bundles also would provide a means whereby functionally similar motoneurons can receive and integrate similar synaptic inputs, and thus allow these inputs to modulate and coordinate groups of neurons that act as a functional unit. The presence of transverse dendrite bundles interconnecting the longitudinal bundles may permit the fine tuning of motoneuron activity for better coordination of movements involving synergistic and antagonistic muscle groups. PMID- 3350084 TI - Effect of denervation and nerve extract on ultrastructure of muscle. AB - Changes in denervated skeletal muscle result both from disuse and loss of neurogenic trophic substances. It had been shown that administration of nerve extract intramuscularly in rats or systemically in mice prevented the nondisuse component of atrophy in denervated muscle. Amelioration of atrophy was manifested as reduced losses of weight, protein, and cross-sectional areas of fiber in denervated hind-limb muscles. The present study assessed the effects of nerve extract on ultrastructural changes in different types of fiber (as classified by activity of ATPase) in mouse skeletal muscle denervated for 7 days. Denervated and contralateral innervated muscles of treated and untreated mice were examined by electron microscopy, and morphological parameters were quantitated by stereological techniques. Denervated muscles exhibited smaller reductions of several ultrastructural changes in treated than in untreated mice including sizes of mitochondria, and percentage volume per fiber of mitochondria, sarcoplasmic reticulum, and t-tubules. The magnitude of the myotrophic effects varied in the different types of fiber, with amelioration of between 50 and 95% of the postdenervation changes. PMID- 3350085 TI - Functional consequences of experimental nerve lesions: effects of time, location, and extent of damage. AB - The purpose of this experiment was to investigate the part played by each of the four fundamental components of a nerve in functional recovery from injury. In order to single out the role of cellular elements (the neurites), tissular elements (the Schwann cells), structural elements (the basal lamina tubes), and the blood-nerve barrier, various crush lesions were made on sciatic nerves of rats and functional recovery was studied. I examined the effects of the location and number of damaged sites and of the time elapsed between successive injuries. Results were assessed for a post-operative period of 2.5 months by studying tracks obtained from walking rats. This study suggested that (a) as far as neurites were concerned, the location of injury influenced the recovery pattern but the extent of damage did not; (b) the extent of damage to the Schwann cells had no measurable influence; (c) long-lasting deficits could be attributed to disruption of the basal lamina tubes, and (d) damage of the blood-nerve barrier could be responsible for slight and temporary disruption of the recovery pattern. I did not observe any of the possible beneficial effects of conditioning lesions described by some authors. This study emphasized the role of the basal lamina tubes in nerve injury and regeneration. PMID- 3350086 TI - Contrasting properties of medial septal neurons projecting to hippocampus or interpeduncular nucleus in the rat. AB - The properties of neurons of the medial septal nucleus and of the nucleus of the diagonal band of Broca which project to hippocampus or to interpeduncular nucleus were compared in rats anesthetized with urethane. Neurons projecting to the interpeduncular nucleus had a slower conduction velocity and a lower spontaneous discharge rate. In contrast, their responses to various putative neurotransmitters (glutamate, GABA, acetylcholine) were similar. In a few cases, neurons projecting to both structures (i.e., with branched axons) were observed. Both septohippocampal and septointerpeduncular pathways are known to be partly cholinergic. Our results show that they originate from two independent populations of medial septal-nucleus of the diagonal band of Broca neurons with different physiologic properties. PMID- 3350087 TI - Functional consequences of experimental nerve lesions: effects of reinnervation blend. AB - In spite of a constant and irrepressible growth of sprouts from the proximal stump of peripheral nerves that have been injured, functional recovery varies greatly from one case to another. To try and understand the reasons for this variability, I have proposed a novel view of the events occurring in a regenerating nerve; based on this view, a probability model was designed that could represent all situations observed after nerve injury. This model, described elsewhere, is based on the assumptions that the guidance role of basal lamina tubes is fundamentally important and that when this guidance fails, regrowth is random. In the present study, this model was tested; behavioral results were measured after various procedures on rat sciatic nerve, and these data were compared with results predicted for similar injuries through the probability model. A good correlation was observed between theoretical and experimental results, indicating that the probability model was reliable. Using this model as the basis for my conclusions, the inconsistent results of current surgical techniques of nerve repair were tentatively explained. PMID- 3350088 TI - The deafferentation syndrome in the rat: effects of intraventricular apomorphine. AB - A deafferentation syndrome, produced in rats by dorsal root ganglionectomies, is expressed as scratching of partially deafferented limb areas and/or biting of anesthetic limb areas. This self-mutilation may be objective evidence of dysesthesias, thus serving as an experimental model to study chronic dysesthesias and/or pain from deafferentation in man. This study included behavioral observations of the syndrome and the effects of intraventricular apomorphine, a dopamine agonist, on its expression. Thirty-eight female Sprague-Dawley rats underwent unilateral C5-T2 dorsal root ganglionectomies followed immediately by stereotactically guided cannulation of the right lateral ventricle in 20 of the rats. For 2 weeks continuously via an osmotic minipump, 10 rats received apomorphine (5 micrograms/h) and 10 others received L-ascorbate (the vehicle). Rats with ganglionectomies only, as well as those receiving L-ascorbate, demonstrated early onset, more severe and later onset, less severe biting groups (P less than 0.05 Mann-Whitney U). Animals receiving apomorphine exhibited low autotomy scores irrespective of time of bite onset. Among the control groups, but not the experimental animals, the earlier the onset of biting, the more severe was the autotomy. The rats receiving vehicle via the minipump had earlier bite onsets than the rats in the ganglionectomy only group. This may indicate that the presence of the minipump is a stress which can accelerate the onset of biting. Intraventricular apomorphine can affect the deafferentation syndrome in the rat; it seems to decrease the level of autotomy and disrupt the relationship of bite onset with degree of biting. PMID- 3350089 TI - Kindling in the deep prepyriform cortex of the rat. AB - Rats were electrically kindled in deep prepyriform cortex (DPC) and in immediately surrounding areas, pyriform cortex, and the basolateral amygdala in an effort to identify an area of the basal forebrain crucially involved in epileptogenesis and the kindling of seizures. Picomolar quantities of carbachol were also microinjected into DPC. All of these areas kindled at equivalent rates. Injection of picomolar quantities of carbachol failed to evoke epileptiform spiking, but injection of nanomolar quantities of carbachol usually evoked epileptiform spiking. Bilateral radiofrequency lesions of the DPC did not affect the rate of electrical kindling of the basolateral amygdala. We conclude that the DPC kindles readily at a rate that is similar to that of surrounding basal forebrain tissue and that the integrity of the DPC is not necessary for basolateral amygdaloid kindling. PMID- 3350090 TI - Cordotomy-denervation interactions on contractile and myofibrillar properties of fast and slow muscles in the rat. AB - Cordotomy-denervation interactions were studied on contractile and myofibrillar properties of slow (soleus) and fast (extensor digitorum longus) muscles of the rat. The spinal cord was transected midthoracically in neonatal (2-day-old) animals. Two months after birth, a unilateral transection of the sciatic nerve was carried out in both cordotomized and control animals. Five weeks after denervation, contractile properties were tested isometrically in vitro; myofibrillar properties were assessed by histochemical staining of the muscle fibers and by electrophoretic analysis of the myosin heavy chain composition. The following results were obtained: (i) In cordotomized animals the contraction time of the soleus was significantly shorter (-23.3% on average) than that in the control animals and this shortening was accompanied by a proportional slow-to fast shift in myofibrillar properties. (ii) The extensor digitorum longus properties were not significantly different in the control and cordotomized animals. (iii) Denervation in control animals was followed by a marked increase of contraction and half-relaxation times in the extensor digitorum longus, whereas in the soleus only the half-relaxation time was significantly increased; myofibrillar properties in the soleus showed an appreciable slow-to-fast shift, whereas in the fast muscle the main change was an increase in type 2A fibers to the detriment of type 2B. (iv) In cordotomized animals, denervation caused the soleus contraction time to increase to control values, whereas myofibrillar properties shifted to an even faster pattern; in the extensor digitorum longus denervation caused the same changes seen in the control animals. The results showed that cordotomy at birth caused the soleus to develop as a faster muscle than in the control animals. The concurrent effects of cordotomy and denervation on the myofibrillar properties of the soleus suggest that the slow-to-fast change in these properties is a common consequence of the reduction in the level of motor activity. The opposite effects of the two experimental conditions in the soleus contraction time support the view that the contractile alterations that follow denervation mainly reflect alterations in the muscle activation process. PMID- 3350091 TI - Visual thalamocortical projections in normal and enucleated rats: HRP and fluorescent dye studies. AB - Visual thalamocortical projections of neonatally enucleated and control rats were studied after tracer injections into the striate and peristriate areas of adult pigmented rats. The distribution of retrogradely labeled neurons in the visual thalamic nuclei was mapped after (a) small localized injections of horseradish peroxidase into either area 17, 18, or 18a and (b) simultaneous injections of three different retrograde tracers (fast blue, HRP, and diamidino yellow) into the anterior, medial, and posterior regions of area 17. It was shown in both normal and neonatally enucleated rats, that the dorsal lateral geniculate nucleus projects to the striate cortex (area 17), whereas the laterodorsal thalamic nucleus of the lateral thalamus projects to the medial peristriate area 18, and the lateral posterior thalamic nucleus has a projection to the lateral peristriate area 18a. Additionally, both extrageniculate visual thalamic nuclei project to area 17. Neurons in the dorsoanterior region of the dorsal lateral geniculate nucleus project to the posterior part of area 17, while neurons in the ventroposterior region of the nucleus send their axons to the anterior part of area 17. A similarly inverted projection of anterior and posterior divisions of the lateral posterior thalamic nucleus to visual area 18a was detected. In enucleated rats, the general topography of the projections from the thalamic neurons to the striate and peristriate cortices was indistinguishable from that in the controls. Nonetheless, there was noticeable shrinkage of the dorsal lateral geniculate nucleus and lateral thalamus and a significant decrease in the size of the somata of projecting neurons. Mean somal area of the HRP-labeled neurons in the dorsal lateral geniculate nucleus of enucleated rats was reduced by 19.0% and the mean maximum cell diameter by 14.3% compared with controls. PMID- 3350092 TI - Hydrocortisone differentially alters lesion-induced axon sprouting in male and female rats. AB - Hydrocortisone was administered to young adult male or female rats after removal of the entorhinal cortex. Lesion-induced outgrowth of the commissural associational afferent fibers in the hippocampus was quantitated. The glucocorticoids caused a significant decline in axon sprouting in the male subjects and a significant increase in outgrowth in female subjects. Depending on the sex, the hormonal effects on lesion-induced axonal growth are markedly different in the rat. PMID- 3350093 TI - Effect of electroconvulsive shock on the slow components of the brain stem auditory evoked potential. AB - The effects of electroconvulsive shock on the slow components of the brain stem auditory evoked potential were investigated in the rat during the ictal and the immediate postictal periods. Shock did not significantly alter any aspect of the slow positive-negative complex which underlies the high-frequency waves of the brain stem auditory evoked potential. However, a succeeding potential of probable cortical origin was markedly reduced in amplitude and its peak latency was temporarily increased. PMID- 3350094 TI - Glucose depletion hyperpolarizes guinea pig hippocampal neurons by an increase in potassium conductance. AB - Superfusion of guinea pig hippocampal brain slices with a glucose-free solution induced a membrane hyperpolarization and an increase in input conductance of neurons in the CA3 region. Under voltage clamp, glucose depletion induced an outward current with a reversal potential near the K+ equilibrium potential. The action of glucose depletion was different from the effect of ouabain, indicating that low-glucose-induced changes in the membrane conductance are primarily due to alterations in cell metabolism rather than due only to an inhibition of the Na+/K+ pump. PMID- 3350095 TI - Lesions rostral and caudal to the trigeminal motor nucleus and their effects on the jaw-opening reflex of the cat. AB - Brain stem lesions placed immediately rostral to the trigeminal motor nucleus of the cat abolish the visible jaw-opening reflex produced by electrical stimulation of the periodontal ligaments. These lesions also greatly diminish the amplitude of the electromyographic response recorded from the anterior belly of the digastric muscle. This attenuation could not be modified by injections of systemic strychnine (a glycine antagonist). Lesions placed immediately caudal to the trigeminal motor nucleus also abolished the visible reflex and greatly reduced the amplitude of the digastric response, but in this case, the attenuated response was slightly augmented by strychnine. These data suggest that glycinergic inhibitory neurons form part of the rostral pathway that regulate jaw opening motor neurons. PMID- 3350096 TI - Interrelationship of thermal and sleep-wakefulness changes elicited from the medial preoptic area in rats. AB - The study investigated the possible interrelationship between changes in sleep wakefulness and body temperature, primarily induced by manipulation of the noradrenergic system in the medial preoptic area. Saline, norepinephrine, and its alpha- and beta-blockers were injected in the medial preoptic area and in some control areas of rats, during their sleeping and active periods. 5 Hydroxytryptamine was injected in the medial preoptic area in another group of animals. Simultaneous changes in sleep-wakefulness and the body temperature were continuously recorded. Norepinephrine produced hypothermia and arousal, whereas alpha-adrenergic blockers induced hyperthermia and sleep. These changes in body temperature and in sleep-wakefulness did not follow an identical time course. 5 Hydroxytryptamine induced hyperthermia without affecting sleep-wakefulness. It is suggested that there are different neuronal mechanisms in the medial preoptic area that bring about the drug-induced changes in temperature and sleep wakefulness. PMID- 3350097 TI - Scanning electron microscopic study of the neuromuscular junction of dystrophic mice. AB - The structure of the end-plate regions of normal and dystrophic 3-month-old mice were studied by scanning electron microscopy after the presynaptic terminals were removed by hydrochloric acid treatment. Quantitative analysis revealed that the end-plate area correlated positively with the muscle fiber diameter in both the normal and dystrophic animals. However, the motor end-plate area was significantly smaller in the dystrophic mice. The total length of the primary cleft of an end-plate correlated positively with the end-plate area and with the muscle fiber diameter in both normal and dystrophic mice. However, the total length of the primary cleft of an end-plate was significantly shorter in dystrophic mice, especially in large-diameter muscle fibers. Finally, the end plate of dystrophic mice was characterized by shorter primary clefts with less branching points. These changes of several morphometric characteristics of the postsynaptic membrane suggest that the functional denervation of the mouse dystrophic neuromuscular junction has a postsynaptic origin. PMID- 3350098 TI - Internodal Schwann cell fingers in the ventral spinal roots in mice: incidence and relationship to the diameter of myelinated fibers. AB - Internodal Schwann cell fingers were present in the lumbar, cervical, and thoracic spinal roots of adult mice at the age of 3 months, but they were not recognized in five mice examined at the age of 3 weeks. In the L4 ventral roots of ICR mice aged 3 months, the incidence of internodal Schwann cell fingers was 0.79% at the central-peripheral transitional zone and 2.43% at the distal regions, respectively. The ratio of axon diameter to total fiber diameter of myelinated fibers with internodal Schwann cell fingers was lower than that of fibers without them. Therefore, we conclude that internodal Schwann cell fingers are probably related to the developmental increase in the thickness of the myelin sheaths in the ventral spinal roots at all levels of the spinal cord. PMID- 3350099 TI - Neurogenic stimuli alter preoptic area and amygdala unit activity: central effects of olfactory projections on paraventricular nucleus units. AB - Unit responses were recorded in the preoptic area and amygdala of conscious male rats during exposure to stressful neurogenic stimuli. Olfactory stimulation elicited increases in preoptic area activity on all occasions and also increased activity in the intercalating, medial, and basomedial nuclei of the amygdala, but not in other regions. Acoustic stimulation had less specific effects, even inhibiting unit activity in the central amygdala. A separate series of experiments using urethane-anesthetized rats was carried out to examine the effects of electrical stimulation of the medial amygdala and olfactory tubercle on single-unit activity within the hypothalamic paraventricular nucleus. Inhibition was the predominant response following olfactory tubercle stimulation while excitatory responses predominated following stimulation of the medial amygdala. This was the case particularly for those paraventricular nucleus units identified as projecting to the median eminence (P less than 0.005 vs unidentified cells). The results obtained may be related to the neural regulation of adrenocortical activity as well as higher central nervous activity and have been discussed within these contexts. PMID- 3350100 TI - Cerebral blood flow in schizophrenia. AB - The regional cerebral blood flow of 27 young (mean age 24 years) schizophrenic patients was measured using the intravenous 133Xe method. The results were compared with those obtained from a group of age- and sex-matched control subjects. The main findings of the study were as follows: (a) the gray matter mean values of cerebral blood flow for both hemispheres were slightly but significantly lower in the schizophrenic group, and the statistical variance was significantly greater in the patients than in the control group; (b) the mean value for each hemisphere was found to be significantly lower for the right hemisphere; (c) the physiological hyperfrontal patterns of cerebral blood flow were identical in patients and controls; (d) visual hallucinations were associated with a reduction of regional cerebral blood flow in the temporo occipital regions; and (e) antipsychotic medication did not appear to influence gray matter cerebral blood flow. PMID- 3350101 TI - Schistosomatium douthitti: biochemical and morphological effects of an experimental infection in mice. AB - The pathophysiological changes that occur in mice experimentally infected with Schistosomatium douthitti were studied. Male ICR mice, 6-8 weeks in age, were exposed to 100 cercariae of S. douthitti from infected snails (Lymnaea catascopium) and sacrificed weekly for a total of 13 weeks. Liver homogenates, serum samples, and histological sections of liver tissue were examined. Results showed that body weights of animals with prepatent infections were higher than those of corresponding controls. After patency, which occurred at 5 weeks, body weights were lower and liver weights were higher resulting in significantly increased liver weight/body weight ratios. Hematocrit values declined progressively in patent infections. Total cholesterol in liver was generally higher in the parasitized groups reaching significance during patency. Values rose with age in both control and parasitized groups, but sooner in the latter. Free cholesterol was increased in the liver of animals with patent infections. Total lipid content of the liver was reduced in the infected animals throughout the study. Both liver glycogen and serum glucose levels in the infected animals rose over the control values. The activity of alkaline phosphatase (E.C.3.1.3.1) was elevated in liver tissue of infected mice. Glutamic-pyruvic transaminase (E.C.2.6.1.2) activity was higher in serum but lower in the livers of animals harboring patent infections. Total bile salt concentration in parasitized animals did not differ appreciably from control values; however, gallbladders were enlarged five times in the infected animals. Histologically, liver sections from infected mice showed granulomas in various stages of formation and degeneration. Granulomas contained from 1 to 40 schistosome eggs. After 6 weeks of infection, granulomas were characterized by many neutrophils and monocytes. Few lymphocytes and eosinophils were present. As the granulomas developed, fibroblasts and connective tissue became more prominent. Glycogen deposits were observed surrounding granulomas and were increased in older infections. Adult worms contained abundant amounts of glycogen and cholesterol in their parenchymal tissues. PMID- 3350102 TI - Schistosoma mansoni: sterol and phospholipid composition of cercariae, schistosomula, and adults. AB - The sterol and phospholipid composition of cercariae, schistosomula, and adult Schistosoma mansoni was analyzed by gas-liquid chromatography and high performance liquid chromatography (HPLC). Cercariae and schistosomula contained cholesterol, desmosterol, campesterol, stigmasterol, and beta-sitosterol while adults contained only cholesterol. In all stages cholesterol comprised greater than 50% of the total sterols, and in cercariae and schistosomula desmosterol comprised 38 and 21% of the total sterols, respectively. The other three sterols, campesterol, stigmasterol, and beta-sitosterol, made up approximately 10% of the total. The same five sterols found in cercariae and schistosomula were present in the hepatopancreas of uninfected snails but with a much higher desmosterol concentration in the parasite, 38%, than in the snail, 2%. As in cercariae and schistosomula the three minor sterols comprised approximately 10%. Thus, the sterol composition of cercariae and schistosomula was similar but not identical to that of the snail host. Phosphatidylcholine was the major phospholipid of all three stages (50%) as determined by two HPLC procedures. The remaining phospholipids consisted of phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. In addition, in adults there were small quantities of sphingomyelin and lysophosphatidylcholine. The percentage of each phospholipid was similar among stages with the exception of a slight increase in phosphatidylserine in adults compared to cercariae and schistosomula. These results show that a characteristic lipid composition is found in cercariae, schistosomula, and adults. PMID- 3350103 TI - Heligmosomoides polygyrus: retarded development and stunting of larvae by antibodies specific for excretory/secretory antigens. AB - The migration of young adult-stage Heligmosomoides polygyrus from beneath the muscularis mucosa to the lumen of the intestine was monitored to compare the rate of development and maturation of larvae in normal and previously infected mice. The development of surviving larvae was significantly retarded in mice that had experienced one or more previous infections and the adult worms arising from a challenge infection were stunted and appeared anaemic. Identical effects were observed with worms recovered from mice that had been injected with immune mouse serum at the time of challenge, and the magnitude of these effects was related to the amount of serum given. Larval maturation was also retarded in mice immunized with larval excretory/secretory (ES) antigens, even though the antibody response was poor due to the very small (submicrogram) amounts of antigen available for injection. In contrast, larvae developed at a normal rate in mice that had been hyperimmunized with killed exsheathed larvae. These mice had serum antibody titres against both "internal" and cuticular antigens similar to those of highly immune (4x-infected) mice, but they had no detectable antibody against ES antigens. The results indicate that the growth and development in vivo of H. polygyrus larvae are retarded by antibodies specific for larval ES antigens. Stunting is permanent, with female worms being affected more severely than males and egg output per worm correspondingly reduced. PMID- 3350104 TI - Enhanced solubilization of immunoreactive proteins from Brugia malayi adult parasites using cetyltrimethylammonium bromide. AB - To determine an optimal method for extracting immunoreactive proteins from filarial parasites, we have subjected Brugia malayi adult worms to a variety of solubilization regimens and compared the results. The parasites were extracted in one of seven detergents (including anionic, cationic, nonionic, and zwitterionic compounds) under varying conditions of pH, detergent concentrations, and incubation time. The individual antigen preparations were then compared both by one-dimensional SDS-PAGE and by immunoblotting analysis using a serum pool from individuals resident in an area endemic for lymphatic filariasis. The cationic detergent cetyltrimethylammonium bromide (CTAB) at 1.0% concentration, pH 7.2, consistently solubilized more proteins immunoreactive with the sera tested. Additionally, CTAB never failed to solubilize immunoreactive proteins solubilized by those other detergents or combinations of detergents studied. PMID- 3350105 TI - Brugia malayi: arachidonic acid uptake into lipid bodies of adult parasites. AB - Lipid bodies are non-membrane bound intracellular organelles, which have been recognized morphologically in a diversity of mammalian and nonmammalian cells, but are of uncertain function. In mammalian cells, in addition to serving as a storage site of cholesterol and triglyceride, lipid bodies can be a repository of esterified arachidonic acid. Adult worms of the human filarial parasite Brugia malayi have been found to esterify exogenous [3H]arachidonic acid into parasite phospholipids and neutral lipids. Electron microscopic autoradiography demonstrated that [3H]arachidonate was preferentially incorporated into filarial lipid bodies. The dominant incorporation of arachidonate into lipid bodies of a nematode establishes that lipid bodies are a site of arachidonic acid accumulation in nonmammalian, as well as mammalian, cells. PMID- 3350107 TI - Ascaris suum and Onchocerca volvulus: S-adenosylmethionine decarboxylase. AB - Putrescine-dependent S-adenosylmethionine decarboxylase (EC 4.1.1.50) was demonstrated in Ascaris suum and Onchocerca volvulus; activation was found to be about fourfold by putrescine. Mg2+ did not affect the enzyme activity. A. suum was taken as a model nematode and its S-adenosylmethionine decarboxylase was partially purified and characterized. The molecular weight was estimated to be 220,000. The apparent Km-value for adenosylmethionine was determined to be 17 microM. Methylglyoxal bis(guanylhydrazone) and berenil competitively inhibited the enzyme activity; the apparent Ki-values were found to be 0.24 microM and 0.11 microM, respectively. The dependence of filarial worms on uptake and interconversion of putrescine and polyamines as well as properties of the S adenosylmethionine decarboxylase, different from the host enzyme, points to the polyamine metabolisms as a useful target for chemotherapy. PMID- 3350106 TI - Leishmania mexicana: effect of concomitant malaria on cutaneous leishmaniasis. Development of lesions in a Leishmania-susceptible (BALB/c) strain of mouse. AB - Effect of concomitant malaria on cutaneous leishmaniasis. Development of lesions in a Leishmania-susceptible (BALB/c) strain of mouse. Experimental Parasitology 65, 269-276. Symptoms of human leishmaniasis vary greatly, ranging from cryptic infections to cases with fatal sequelae. Factors regulating the severity of the disease are largely undetermined. Malaria coincides geographically with leishmaniasis in many areas and the immunosuppressive effects of malaria are well documented. It is therefore plausible that malaria could enhance the course of concomitant leishmaniasis. Interactions between Leishmania mexicana and Plasmodium yoelii were examined in BALB/c mice. Percentage of blood cells infected with P. yoelii and diameter of footpad lesions caused by L. mexicana were the criteria used to assay for disease severity. L. mexicana and P. yoelii infections were each significantly enhanced in dually infected mice when compared to mice infected with either parasite alone. Mortality rates due to the normally nonlethal P. yoelii were high during concurrent infections. PMID- 3350108 TI - Toxoplasma gondii: in vivo and in vitro studies of a mutant resistant to arprinocid-N-oxide. AB - The anticoccidial drug arprinocid and arprinocid-N-oxide, a metabolite produced in vivo, blocked the growth of Toxoplasma gondii in human fibroblasts. The more potent arprinocid-N-oxide inhibited growth by 50% at 20 ng/ml while arprinocid inhibited at 2 micrograms/ml. For both drugs, the host cell was less sensitive than was the parasite. Hypoxanthine did not reverse the antitoxoplasma activity of either drug. We isolated a parasite mutant, R-AnoR-1 that was 16- to 20-fold more resistant to arprinocid-N-oxide than was the wild type RH T. gondii. This mutant was not resistant to arprinocid in vitro. Arprinocid in a daily oral dose of 136 micrograms regularly protected mice against an otherwise fatal infection with RH T. gondii and 55 micrograms had some protective effect. However, all mice infected with R-AnoR-1 and treated with 360 micrograms arprinocid per day died. Since this mutant is fully sensitive to arprinocid, the form of the drug that is therapeutically active in vivo cannot be arprinocid and is likely to be arprinocid-N-oxide. PMID- 3350109 TI - Trypanosoma brucei gambiense: partitioning of glycopeptides of bloodstream and procyclic forms in Triton X-114. PMID- 3350110 TI - Magnetic resonance microscopy: in vivo sectioning of a developing insect. AB - The utility of magnetic resonance imaging vis-a-vis insect morphology and development was investigated. MRI is a noninvasive technique that distinguishes between tissues based on proton content and proton 'environment'. At present a resolution of 100 micron is achievable. The technique avoids fixation artifacts and allows the detection of motion within the organism. PMID- 3350111 TI - Tetrodotoxin slightly shortens action potential duration in ventricular but not in atrial heart muscle. AB - Tetrodotoxin (TTX), at concentrations significantly decreasing maximal upstroke velocity (dV/dtmax) of the action potential, exerted variable effects on action potential duration (APD) in different myocardial preparations. APD was virtually unchanged by tetrodotoxin in the guinea pig atrium, but slightly shortened in the guinea pig ventricle at maximally effective concentrations. In the human ventricle, both dV/dtmax and APD were reduced in the same concentration range of TTX. These results suggest that a TTX-sensitive sodium current significantly contributes to the repolarization phase of the action potential in ventricular but not in atrial heart muscle. PMID- 3350112 TI - Zinc antagonizes the effect of botulinum type A toxin at the mouse neuromuscular junction. AB - Zn2+ (10-100 microM) elevated the frequency of miniature end-plate potentials (MEPPs) in the mouse diaphragm. The effect did not depend on external Ca2+. Botulinum type A toxin (BTXA, 50 ng/ml) abolished MEPPs almost completely within 30 min. Zn2+ (100 microM) restored MEPPs and increased their frequency after they had been abolished by BTXA in Ca2+ -free solutions. The antagonistic effect of Zn2+ in the Ca2+ -free solution was reduced by exposing the diaphragm to the toxin in the Ca2+ -free solutions containing high K+. Thus, the action of BTXA is probably enhanced by depolarization of the motor nerve terminals. PMID- 3350113 TI - Light and temperature affect retinyl ester hydrolase activity and visual pigment composition. AB - Dim light, in combination with high water temperature, resulted in a significant increase in the retinyl ester hydrolase activity in the goldfish retina. This rise in enzyme activity may relate to a selective increase in the availability of retinal chromophores thereby favoring the formation of rhodopsin under these light and temperature conditions. PMID- 3350114 TI - The influence of different nutrients on plasma cholecystokinin levels in the rat. AB - Isocaloric and isovolemic amounts of protein (casein), fat (intralipid) and carbohydrate (saccharose) and an isovolemic control solution of water were administered intragastrically to conscious rats. The plasma CCK levels, determined by a sensitive and specific radioimmunoassay, showed an increment of 6.3 +/- 0.6, 2.7 +/- 0.5, 1.7 +/- 0.4 and -0.9 +/- 0.4 pM, respectively (basal value 2.5 +/- 0.3 pM). The threshold increment of plasma CCK to stimulate pancreatic enzyme secretion by exogenous CCK was found to be 1.5 pM. It is therefore concluded that casein is a potent stimulus for CCK secretion and pancreatic secretion, but that fat and even carbohydrate, although less potent, also produce a CCK increment above the threshold for pancreatic secretion. PMID- 3350115 TI - A pyruvate kinase variant in different mouse transplanted tumors. AB - Mouse transplanted tumors, in contrast to normal tissues, contain a pyruvate kinase (PK) variant sensitive to the inhibitory action of L-cysteine and less sensitive to saturated fatty acids than the normal enzyme. In selected normal and tumor materials two fractions of PK were separated. Fraction A (20-30% (NH4)2SO4 saturation) dominated in normal liver, and fraction B (50-60% (NH4)2SO4 saturation) in skeletal muscles and Ehrlich ascites tumor. Only this fraction B from tumor material was sensitive to L-cysteine, and seems to contain a tumor specific PK variant which might be considered as a marker of neoplastic transformation in a broad spectrum of mouse experimental tumors. PMID- 3350116 TI - Affinity chromatography of glucose dehydrogenase. AB - Porcine liver beta-D-glucose dehydrogenase, a multi-functional protein, has been purified to apparent homogeneity. The enzyme has been separated from the endoplasmic reticulum using Triton X-114 and further purified using NAD to release glucose dehydrogenase from a NADP-linked sepharose column. The purified enzyme is capable of producing both NADH and NADPH in vivo as indicated by kinetic studies. PMID- 3350117 TI - Effect of continuous illumination on secretion of pregnane compounds by the rat ovary. AB - Differences in the secretion of pregnane compounds from rats with follicular polycystic ovaries under constant light and with normal preovulatory ovaries under light-dark conditions were compared. The injection of LH greatly increased the secretion of progesterone. 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one, in both types of ovaries, but the response of the two progesterone metabolites in the polycystic ovaries was low, suggesting low 5 alpha-reductase activity. PMID- 3350118 TI - Forced synthesis of trace amounts of juvenile hormone II from propionate by corpora allata of a juvenile hormone III-producing insect. AB - Corpora allata of the cockroach Diploptera punctata normally synthesize only the isoprenoid juvenile hormone III (JH III). Only under extreme in vitro conditions (absence of carbon sources other than propionate) do they produce trace amounts of the homoisoprenoid JH II in addition to JH III. The specificity of the in vitro synthesis of JH III by D. punctata is thus consistent with the observed lack of homoisoprenoid JHs in this insect. PMID- 3350119 TI - Endogenous inhibitor of ecdysone synthesis in crabs. AB - Attempts to isolate the molt-inhibiting hormone (MIH) of crustaceans from crab eyestalks (ES) resulted in the characterization of xanthurenic acid as an inhibitor of ecdysone biosynthesis in the cultured Y-organ-complex (YOC) homogenate. It was also found that 3-hydroxy-L-kynurenine present in the ES is transformed into xanthurenic acid in the YOC and body fluid. Its mode of inhibitory action in ecdysone biosynthesis is probably inactivation of cytochrome P-450. PMID- 3350121 TI - In vitro assessment of anti-Leishmania immunity of man acquired with a vaccine. AB - Monocytes, obtained from a human volunteer immunized with a Leishmania infantum derived vaccine, when cultured in vitro displayed a strong parasiticidal activity against L. major promastigotes. In addition, immune serum conferred leishmanicidal activities to monocytes of normal, unexposed donors, and to murine macrophages. PMID- 3350120 TI - Aberrant protamine 1/protamine 2 ratios in sperm of infertile human males. AB - Protamines were extracted from the sperm of fertile and infertile human males and the relative proportion of protamines 1, 2, and 3 were determined by scanning microdensitometry following electrophoresis of total protamine in polyacrylamide gels. The proportion of the three protamines was found to be similar in sperm obtained from different normal males. The distribution of protamines in sperm obtained from a select group of infertile males producing an elevated level of large sperm heads, in contrast, was different from that of the fertile males. PMID- 3350122 TI - Parameters affecting the maximum cell concentration of Tetrahymena. AB - In cultures with efficient aeration a maximum cell concentration (MCC) of 6 X 10(5) cells/ml (defined medium) and 5.5 X 10(6) cells/ml (broth) can be reached. By culturing within Millicells with excess supply of medium and efficient removal of waste products a physical limit for MCC of about 13 X 10(6) cells/ml is reached. PMID- 3350123 TI - Intrinsic forces alone are sufficient to cause closure of the neural tube in the chick. AB - An isolated neural plate or a postnodal piece of early chick embryos, when cultured under appropriate experimental conditions, can undergo morphogenetic movements and form tubular structures closely resembling neural tubes of early chick embryos. PMID- 3350124 TI - Steroid hormones enhanced sister-chromatid exchange in cultured CHO cells. AB - The influence of steroid hormones on the induction of sister-chromatid exchange (SCE) in cultured CHO cells was studied. It was observed that estradiol-17 beta, estriol, estrone and ethynyl estradiol treatments enhanced SCE rates compared to the controls. Overall, these compounds produced a dose response effect. The importance of a detailed study on the long-term genetic effects of steroids on mammalian cells is emphasized. PMID- 3350125 TI - A source of cutaneous maternal semiochemicals in the mink? AB - Unique hypertrophic apocrine sweat glands are described in the neck, perineal and inguinal skin of mink kits. These glands enlarge after birth, only to regress rapidly and become vestigal by weaning. No similar phenomenon has been recognized before in mammals. Behavioral studies indicate a possible role for the glandular secretion in maternal recognition of the young. PMID- 3350126 TI - Goniothalamicin and annonacin: bioactive acetogenins from Goniothalamus giganteus (Annonaceae). AB - Using brine shrimp lethality for activity-directed fractionation, goniothalamicin (I), a new tetrahydroxy-mono-tetrahydrofuran fatty acid gamma-lactone (acetogenin), has been isolated from ethanolic extracts of the stem bark of Goniothalamus giganteus Hook. f., Thomas (Annonaceae). This novel compound was found to be cytotoxic and insecticidal and inhibited the formation of crown gall tumors on potato discs. Annonacin (II), the only other reported mono tetrahydrofuran acetogenin, was also isolated; the previously reported 9ASK (astrocytoma reversal) activity of II was confirmed, and II is now also found to be weakly active against 3PS murine leukemia. PMID- 3350127 TI - Cadmium-induced changes in avian renal morphology. AB - The effects of i.m. administered cadmium on growth rate and nephromorphology were studied in young pullets. The growth rate of pullets treated with 0.6 mg Cd2+/kg at 48-h intervals was severely retarded, reaching only 50% of normal growth by 21 days. Such a decrease in growth rate was prevented when cadmium was given with either ferric or magnesium EDTA chelate. Electron micrographs of kidney tissue from cadmium intoxicated birds revealed massive intracellular disorganisation of proximal tubular cells, showing increased vacuolation and dilated endoplasmic reticulum. Mitochondria were few and swollen with reduced cristae. Some disorganisation was noted in the group treated with MgEDTA in conjunction with cadmium, with normal morphology observed in the group treated with FeEDTA plus cadmium. In general, glomerular morphology of intoxicated pullets appeared normal, except that a 25% increase in thickness of the glomerular basement membrane was evident. No such membrane thickening was observed in any of the chelate treated groups. These findings indicate that both chelates can provide certain levels of protection, in terms of growth rate and morphology, from cadmium intoxication. The possible mechanisms by which chelates offer protection have been discussed, but many questions remain unanswered. PMID- 3350129 TI - Spatial variation in response to odorants on the rat olfactory epithelium. AB - We have measured the electro-olfactogram produced by four odorants, nicotine, i pentyl acetate, i-pentanoic acid and cineole from twelve positions on an in vitro preparation of rat olfactory tissue. Each odorant shows a different pattern of response over the twelve positions which can be explained by differences in olfactory receptor populations between regions of the rat olfactory epithelium. The result for nicotine is further evidence that there are olfactory receptors which are stimulated by nicotine when it is presented as a vapour. PMID- 3350128 TI - Ambiquitous behavior of rabbit liver lactate dehydrogenase. AB - Rabbit liver mitochondrial fraction shows lactate dehydrogenase activity. The enzyme can be released from particles by increasing the pH and the ionic strength of the medium. There is a narrow range of pH (6.8-7.4) and ionic strength (20-50 mM NaCl) in which the solubilization sharply increases. It has been shown that divalent anions (SO4(2-) and cations (Mg2+, Ca2+) are highly effective specific solubilizing agents. NADH (1.5 mM) and ATP (1.0 mM) were effective in solubilizing 50% of the enzyme bound, whereas the same concentrations of the analogs NAD+ and ADP had little effect. Cytosolic lactate dehydrogenase bound to the mitochondrial fraction and a saturation of particles by enzyme was observed in all experiments performed. The in vitro binding requires a short period of incubation between the enzyme and particles and the binding is independent of the temperature in the 0-37 degrees C range. Binding was prevented by 0.15 M NaCl. The bound enzyme is approximately 20% less active than the soluble one. The results described give support to the proposal that rabbit liver lactate dehydrogenase has an ambiquitous behavior, like other glycolytic enzymes, which have not a fixed intracellular localization. PMID- 3350130 TI - Electrophysiological properties of the follicle wall in the pig ovary. AB - The transmural potential difference and short-circuit current of the porcine Graafian follicle have been measured in an attempt to test whether antral fluid accumulates as a result of active transport of salt. The values obtained by mounting explants of follicle wall in Ussing chambers were close to zero and the specific electrical resistance was only 59 delta.cm2. The elemental composition of the follicular fluid was similar to that of ovarian venous plasma with the exception of follicular Na+ which was slightly more abundant. Bicarbonate concentrations were slightly lower in follicular fluids. These findings were interpreted as evidence that the follicular wall is a leaky epithelium and, therefore, any charge resulting from net ion transport will be shunted along low resistance paracellular pathways. PMID- 3350131 TI - Intrinsic control of rhabdom size and rhodopsin content in the crab compound eye by a circadian biological clock. AB - Under conditions of constant darkness, rhabdom volume and the amount of visual pigment chromophore show circadian changes in the compound eye of the crab Hemigrapsus sanguineus. The present results indicate that an intrinsic circadian biological clock is involved in the control of the changes. PMID- 3350132 TI - Enhanced reactivity towards flunarizine in cerebrovascular bed of spontaneously hypertensive rats. AB - Cerebral blood flow (CBF) was measured and cerebrovascular resistance (CVR) was calculated in anesthetized spontaneously hypertensive rats (SHR) and normotensive rats (NR) following the administration of incremental dosages of i.v. flunarizine or papaverine. CBF and CVR changes following papaverine were the same in both groups of rats irrespective of the dose of the drug. The effect of flunarizine was much more pronounced in SHR than in NR. The results point out the greater dependency of basal cerebrovascular tone in SHR upon Ca2+ influx into vascular smooth muscle cells. PMID- 3350133 TI - Lack of effect of dihydroergotamine on endothelial and smooth muscle cell proliferation and endothelial cell prostanoid production. AB - The most important effect of dihydroergotamine is venoconstriction, but certain metabolic effects and changes in vessel prostanoid activity have also been suggested. In this study endothelial cell production of 6-keto PGF1 alpha and TxB2 was quantitated in vitro. No evidence of altered prostanoid production was noted after incubation with dihydroergotamine (exposure ranging from 5 x 10(-3) to 5 x 10(-7) g/l). Similarly, no effect of dihydroergotamine on the growth rates of endothelial cells or smooth muscle cells in vitro was documented. PMID- 3350134 TI - Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate. AB - Rat brain homogenate was preloaded with [3H]noradrenaline or [3H]GABA and stimulated with high K+. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [3H]noradrenaline release in the same range of toxin concentrations starting below 10(-10) M. In contrast, release of gamma-amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin. PMID- 3350135 TI - Adenosine-5'-triphosphate levels in experimental CaNT and Fib/t tumours of varying volume and degree of hypoxia. AB - The variation of adenosine-5'-triphosphate (ATP) content per unit mass of tumour, versus tumour volume was measured in vivo under normoxic conditions, using CaNT and Fib/t murine tumours grown in CBA and WHT mice respectively. A monotonically decreasing relation was found. Artificially induced tumour hypoxia resulting from 15 min of clamping was accompanied by reduced ATP levels. PMID- 3350137 TI - Sex chromatin analysis of unstained mouse amniotic cells using brightfield microscopy. AB - Sex chromatin of unstained mouse amniotic cells was identifiable using ordinary brightfield microscopy with optimal setting of the illumination. PMID- 3350136 TI - Aneuploidy of glandular epithelial cells in histologically normal prostate glands. AB - The percentage of aneuploidy in normal prostate glands from subjects 13-38 years old and 45-66 years old ranged from 0-78% and 0-63%, respectively. In contrast to adults, aneuploidy was absent in fetal and postnatal prostates. It is concluded that aneuploidy is a fundamental attribute of histologically normal adult prostate glands. PMID- 3350138 TI - C-band differentiation between the chromosomes of two subspecies of the chironomid midge Chironomus thummi. AB - The metaphase chromosomes of Chironomus th. thummi contain approximately 17% more pericentric C-band heterochromatin than the chromosomes of Chironomus th. piger with 11% heterochromatin. In Ch. th. thummi, the proportion of heterochromatin appeared to be much larger in metaphase chromosomes than in polytene chromosomes. This discrepancy is interpreted as being due to the specific chromosome organization and not as the result of an underreplication of heterochromatin during polytenization. PMID- 3350139 TI - Confirmation of the structure of nisin and its major degradation product by FAB MS and FAB-MS/MS. AB - FAB-MS has been applied to the analysis of a nisin complex and FAB-MS and FAB MS/MS data from the major component used to provide confirmation of the amino sequence and positions of the sulphur-bridged rings in these highly modified peptides. PMID- 3350140 TI - o-Aminoacetophenone, a pheromone that repels honeybees (Apis mellifera L.). AB - o-Aminoacetophenone is a pheromone produced by virgin honeybee queens and released with feces. In small social groups, the pheromone repels and is used to terminate agonistic interactions between queens and workers. PMID- 3350141 TI - Induction of eosinophilic enteritis and eosinophilia in rats by vitamin E and selenium deficiency. AB - Eosinophilic enteritis and eosinophilia, in addition to muscular dystrophy and occasionally liver necrosis, were experimentally induced in male Sprague-Dawley rats with a vitamin E- and selenium-deficient diet (basal diet) for 9 weeks. Cecum and ileum were affected more frequently and severely than other segments of the gastrointestinal tract. Eosinophils were multifocally or diffusely distributed in the intestinal wall but were most severe in the muscular layer and in the submucosa. Eosinophils were also present in stomach, liver with massive hepatocellular necrosis, and skeletal muscle with marked myonecrosis. Eosinophilic enteritis and eosinophilia were not observed in rats fed the basal diet supplemented with either vitamin E (100 or 200 ppm) or selenium (0.1 or 1.0 ppm). Eosinophilic enteritis, eosinophilia, and muscular dystrophy regressed when vitamin E- and selenium-deficient rats were subsequently fed either the vitamin E or selenium-supplemented diet for 4-5 weeks. These findings suggest that vitamin E and selenium deficiency may play a role in the development of a diffuse type of eosinophilic enteritis and eosinophilia. PMID- 3350142 TI - Effects of chronic furosemide treatment on rat exocrine glands. AB - It has been suggested that a defective chloride transport is the primary cellular basis for the disease cystic fibrosis (CF). Therefore, the effects of chronic furosemide treatment on the structure and function of rat exocrine glands were investigated. X-ray microanalysis of the submandibular gland showed an increase in the cellular Ca and Mg concentrations, and a decrease in the cellular Cl concentration. Transmission electron microscopy showed intracellular accumulation of mucus and the presence of mucus in acinar and ductal lumina. The volume of saliva secreted by the submandibular gland after pilocarpine stimulation was markedly reduced in furosemide-treated animals; the salivary concentrations of Na and Ca were higher, and that of K was lower, than in control animals. The protein concentration in submandibular saliva was not significantly affected. The response of the submandibular gland to isoproterenol stimulation was reduced in furosemide-treated animals. In the parotid gland, chronic furosemide treatment caused an accumulation of immature zymogen granules in the acinar cells and a decrease in the cellular Cl concentration. In the pancreas, the acinar lumen was dilated and completely filled with secretory material, and the acinar cells contained less Na and somewhat less Cl than in control animals. The chronically furosemide-treated rat shows a number of parallels with other animal models for CF, in particular the chronically reserpinized rat. There is also agreement with the human disease itself. PMID- 3350143 TI - Complement C5a (desArg) generation in serum exposed to damaged aortic endothelium. AB - Complement activation by injured endothelial cells was investigated using ex vivo rabbit thoracic aortas as a source of endothelium and a neutrophil aggregation (NA) bioassay to detect the complement cleavage product C5a (desArg). Endothelium, oxygen-starved by incubating aortas 30 min with Tyrode's buffer, activated complement as demonstrated by a 57% increase in the NA response induced by serum from buffer-treated aortas as compared to serum from untreated control aortas. Incubation of MgEGTA serum in injured aortas resulted in a 27% (P less than 0.025) weaker NA response than normal serum, indicating participation by both classical and alternative pathways of complement activation. Serum from aortas incubated 30 min with 100 micrograms/ml cholestane-3 beta, 5 alpha, 6 beta triol, a cytotoxic cholesterol oxidation derivative, induced a NA response comparable to that from serum from aortas treated 30 min with Tyrode's buffer. Heat inactivation of serum prior to aortic incubation abolished NA activity and serum incubated in deendothelialized aortas lacked NA activity. Fractionation of serum samples from these experiments on Sephadex G-100 revealed a single peak of NA activity corresponding to the molecular weight of C5a (desArg). Endothelial cell injury was demonstrated by the inability to exclude Trypan blue dye and by scanning electron microscopy. These data demonstrate that damaged arterial endothelium can effectively activate the complement system, resulting in the production of an anaphylatoxic inflammatory mediator. PMID- 3350144 TI - Involution of thymic epithelium and low serum thymulin bioactivity in weanling mice subjected to severe food intake restriction or severe protein deficiency. AB - The volume of epithelium in the cortex and in the medulla of the thymus was compared in four groups of weanling male and female CBA/J mice. Well-nourished controls (C), food intake restricted (R), and animals given a low-protein diet ad libitum (LP) were fed from 23 to 37 days of age. Baseline controls (B) were studied at 23 days of age. Epithelial volume fraction was estimated for each group by point-counting morphometry on electron micrographs. Other mice were used to obtain group mean estimates of thymic index (mg/g live weight) and volume fraction of cortex and medulla (light microscope-level point-counting morphometry). Cortical and medullary epithelial volumes were calculated for each animal examined by electron microscopy by obtaining the live weight and applying, in sequence, the group mean thymic index, an assumed thymic density of 1.0 mm3/mg, the group mean cortical or medullary volume fraction, and the measured cortical or medullary volume fraction for that animal. Serum thymulin bioactivity was also measured in C, R, and LP mice. The results reveal thymic epithelial involution in the two most common rodent models of malnutrition, and suggest that this may contribute to the low serum thymulin levels found in malnourished experimental animals and humans. PMID- 3350145 TI - The effect of combined deendothelialization and hypercholesterolemia on some arterial lysosomal and glycolytic enzymes and lactate in rabbits. AB - In eight New Zealand white male rabbits the abdominal aorta and one iliofemoral artery was balloon deendothelialized (group A). After 2 weeks they were kept for 6 weeks on a high cholesterol diet together with eight unoperated rabbits (group B). Eight more rabbits were kept on a commercial diet only (group C). The degree of atherosclerosis was much higher in the deendothelialized Group A vessels than in the uninjured group B vessels. The activity of lactate dehydrogenase and of the rate-limiting glycolytic pyruvate kinase was significantly increased and the activity of lipoamide dehydrogenase decreased in the group A aortas. In the iliofemoral arteries a similar but statistically insignificant tendency was detected. There was no significant difference, however, in aortic lactate between the three groups. Thus, local hypoxia did not significantly contribute to the high degree of atherosclerosis in the group A animals in spite of the enzyme activity differences. Previous experience of the authors, using arterial microcathode pO2 measurements, indicates that following deendothelialization an adaptive proliferation of nutrient vessels and increased arterial oxygenation takes place. The average activity of the lysosomal N-acetyl-beta-glucosaminidase was five times and that of beta-glucuronidase, seven times higher in the Group A than Group B aortas; in the iliofemoral arteries the differences were even larger. The huge elevation of these hydrolases, which are involved in glycosaminoglycan catabolism, provides indirect indication that accumulation of glycosaminoglycans and possibly their ability to form complexes with apoB containing lipoproteins played a major role in the much increased degree of atherosclerotic lesions in the Group A rabbits. PMID- 3350146 TI - Two adjacent cysteine residues in the C-terminal cytoplasmic fragment of bovine rhodopsin are palmitylated. AB - Covalent coupling of bovine rhodopsin to CPG-thiol glass was used for separation of CNBr peptides. It is shown that cysteine residues 322 and 323 in the C terminal cytoplasmic fragment of rhodopsin are modified with palmitic acid. PMID- 3350147 TI - Low frequency electric and magnetic fields have different effects on the cell surface. AB - There is a considerable controversy over the nature of weak electromagnetic-field effects in living organisms. Part of the controversy can be traced to a lack of understanding of whether electric or magnetic fields are involved in producing bioeffects. We find that both 60 Hz electric and magnetic fields alter the cell surface of Physarum polycephalum. Exposure to electric fields increases the negative charge on the cell surface while magnetic-field exposure decreases the hydrophobic character of the surface. These effects appear to be additive and independent of the waveform of the applied fields. PMID- 3350148 TI - Identification of the phosphorylated beta-tubulin isotype in differentiated neuroblastoma cells. AB - The tubulin molecule consists of an alpha- and a beta-subunit, each of which exists in several isotypic forms. It has been previously shown that one of the isotypes of neuroblastoma beta-tubulin is phosphorylated at a serine residue in vivo [(1985) J. Cell Biol. 100, 764-774]. Here we identify the phosphorylated isotype as beta 2 (type III). Moreover, the large size of the phosphorylated tryptic peptide and sequence comparisons of vertebrate beta-tubulins suggest that one of the two serines in positions 444 and 446 is the phosphorylated residue. Our results raise the possibility that beta 2-tubulin differs functionally from the other beta-tubulin isotypes. PMID- 3350150 TI - A novel protein, p19/6.8, specific for cardiac and slow skeletal muscle. AB - Upon in vitro translation of mRNAs from slow (soleus) muscles of the mouse a hitherto undescribed translation product has been detected that was absent from fast skeletal muscles and was termed p19/6.8 according to its position in 2 dimensional gels. mRNA for p19/6.8 was also found in the ventricle of the heart. p19/6.8 was not detectable by Coomassie blue staining but could be characterised by fractionation of in vivo labelled muscle tissue. It was found to sediment with the particulate fraction at 14,000 x g. The expression of p19/6.8 mRNA appears to be down-regulated in muscles with phasic activity. PMID- 3350149 TI - Biosynthesis of sialosyllactotetraosylceramide in human colorectal carcinoma cells. AB - A monosialoganglioside, IV3-NeuNAcLcOse4Cer, has recently been detected in colorectal carcinoma cells, small cell lung carcinoma cells, embryonal carcinoma cells and in human brain extracts. We report here the presence of a CMP-sialic: LcOse4Cer sialyl transferase activity in subcellular membrane fractions of the human colorectal carcinoma. SW1116, which recognizes the non-reducing terminal galactosyl moiety of lactotetraosylceramide. A convenient method for structural analysis of picomolar quantities of the radioactive enzymatic product(s) using bacterial endoglycoceramidase, sialidase and a viral sialidase is presented. PMID- 3350151 TI - Proton NMR resonance assignments and surface accessibility of tryptophan residues of a dimeric phospholipase A2 from Trimeresurus flavoviridis. AB - Proton NMR spectra of a dimeric phospholipase A2 from Trimeresurus flavoviridis have been recorded. N-1 proton resonances of the tryptophan indole rings have been detected and assigned to specific positions, Trp-3/Trp-30, Trp-68 and Trp 108, by comparing the spectra of the enzyme derivatives with tryptophans oxidized to differing extents. Photo-CIDNP experiments have revealed that Trp-68 and Trp 108 are exposed while Trp-3 and Trp-30 are buried in the molecule. This is consistent with the X-ray crystal structure of a homologous phospholipase A2 from Crotalus atrox where residues 3 and 30 are located at a dimer interface, but inconsistent with the results of stepwise oxidation of tryptophan residues. PMID- 3350152 TI - Physiological roles of animal succinate thiokinases. Specific association of the guanine nucleotide-linked enzyme with haem biosynthesis. AB - The discovery of two distinct succinate thiokinases in mammalian tissues, one (G STK) specific for GDP/GTP and the other (A-STK) for ADP/ATP, poses the question of their differential metabolic roles. Evidence has suggested that the A-STK functions in the citric acid cycle in the direction of succinyl-CoA breakdown (and ATP formation) whereas one role of the G-STK appears to be the re-cycling of succinate to succinyl-CoA (at the expense of GTP) for the purpose of ketone body activation. A third metabolic participation of succinyl-CoA is in haem biosynthesis. This communication shows that in chemically induced hepatic porphyria, when the demand for succinyl-CoA is increased, it is the level of G STK only which is elevated, that of A-STK being unaffected. The results implicate G-STK in the provision of succinyl-CoA for haem biosynthesis, a conclusion which is further supported by the observation of a high G-STK/A-STK ratio in bone marrow. PMID- 3350154 TI - Prevention of infertility. PMID- 3350153 TI - The striatum and cerebral cortex express different muscarinic receptor mRNAs. AB - The existence of four distinct muscarinic acetylcholine receptor genes (m1-mr) has recently been demonstrated. cDNAs for three of these receptors have been cloned from brain (m1, m3, m4) and one from heart (m2). To gain some understanding of the physiological role of the brain muscarinic receptors, we mapped the distribution of their mRNAs in rat brain by in situ hybridization. These mRNAs are barely detectable in the hindbrain and cerebellum. Within forebrain, each mRNA has a strikingly different pattern of distribution. The highest levels of m1 mRNA are in the cerebral cortex and hippocampus followed by the striatum. m3 mRNA is also prominent in the cerebral cortex, but has very low levels in the striatum. Conversely, the levels of m4 mRNA are highest in the striatum. Since the cognitive effects of muscarinic drugs have been localized to the cerebral cortex and hippocampus, and their psychomotor effects to the striatum, these data suggest that the muscarinic receptors which subserve these responses may be different gene products. Finally, we show that these muscarinic receptors can be distinguished pharmacologically, suggesting that it may be possible to develop drugs for the selective treatment of the psychomotor vs cognitive difficulties of Parkinson's and Alzheimer's disease, respectively. PMID- 3350156 TI - Luteal phase salivary progesterone concentrations in ovulation-induced cycles. AB - Serial paired plasma and salivary progesterone (P) levels were determined in 21 ovulation-induced cycles of 13 women and in 162 luteal saliva samples of 21 normal cycling women. Mean +/- standard error of the mean (SEM) salivary P levels in all ovulation-induced cycles were similar to normal cycles and were 294 +/- 31.5 to 499 +/- 75 pg/ml, whereas the corresponding plasma P levels were 24.9 +/- 5.0 to 51.4 +/- 16.6 ng/ml. Paired plasma and salivary P levels correlated significantly in women induced with clomiphene citrate (r = 0.82), follicle stimulating hormone (r = 0.80), human menopausal gonadotropins (r = 0.78), and in those who became pregnant (r = 0.95). Luteal phase salivary P levels were 1.0% to 1.3% of the corresponding plasma levels in ovulation-induced cycles. These findings indicate that salivary P may be a useful and convenient alternative to plasma P for assessing ovulation. PMID- 3350155 TI - Fertility after ectopic pregnancy in relation to background factors and surgical treatment. AB - To study the importance of certain background factors and surgical treatment, the obstetric outcome in 205 women consecutively treated for ectopic pregnancy was analyzed by means of questionnaires 4 to 5.5 years after surgery. The response rate was 83.4% and, among women desiring pregnancy (n = 112), the total pregnancy rate was 75.9% and the delivery rate 53.6%. The total incidence of repeat ectopics was 27.3%, and the proportion of women who had a repeat ectopic pregnancy but no delivery was 20.5%. Six of seven women having an ectopic pregnancy with a copper intrauterine contraceptive device in situ had a normal delivery during the follow-up period. The subsequent fertility among nonresponders appeared lower than among responding women. A number of background factors present at the time of surgery were correlated to subsequent infertility, e.g., history of infertility and previous abdominal surgery. Conversely, there was no correlation between the fertility outcome and the type of operative procedure. PMID- 3350157 TI - The effect of deglycosylated human chorionic gonadotropin on corpora luteal function in healthy women. AB - Fourteen healthy young women were studied through a control and a treatment menstrual cycle in two series of experiments. In the first series, they were given one of four doses of deglycosylated human chorionic gonadotropin (hCG) as a 24-hour infusion during the mid-luteal phase of the cycle. In these studies, there were no significant alterations of the length of the luteal phase of the treatment cycle, and there was no decrease in serum progesterone (P) during the infusion. In fact, serum P increased during the infusion. In the second series of studies, five subjects were given a 48-hour infusion of normal saline during the control cycle, and a 48-hour infusion of deglycosylated alpha-intact beta-hCG during the treatment cycle, both being administered during the mid-luteal phase. Treatment did not alter luteal phase duration and, again, increased serum P. It is concluded that deglycosylated preparations of hCG are not clinically useful as luteinizing hormone antagonists, probably because of residual agonist activity. PMID- 3350158 TI - Direct effects of clomiphene citrate on the steroidogenic capability of human granulosa cells. AB - The effects of clomiphene citrate (CC), 17 beta-estradiol (E2), and human chorionic gonadotropin (hCG) on the accumulation of progesterone (P) and 20 alpha hydroxy-4-pregnen-3-one (20 alpha-OHP) in cultured human granulosa cells (GC) were examined. In addition, the metabolism of [4-14C]pregnenolone and accumulation of [4-14C]P in response to CC and E2 were determined. The authors conclude the following: (1) the dose-dependent inhibition of P and 20 alpha-OHP production by CC in GC was not reproduced by E2, (2) hCG abolished these effects of CC, (3) these inhibitory actions of CC were not associated with altered 3 beta hydroxysteroid dehydrogenase activity nor P catabolism indicating that, (4) these actions by CC on the GC occur at some step(s) during steroidogenesis preceding the formation of pregnenolone. These findings may explain, at least in part, the luteal deficiency experienced by women treated with CC, and they also provide a rationale for the use of hCG supplementation during ovulation induction with CC. PMID- 3350159 TI - The efficiency of human reproduction after in vitro fertilization and embryo transfer. AB - Two hundred ninety-seven nonpregnant patients were used to study the possibility of early transient implantation as a parameter of the efficiency of in vitro fertilization (IVF) procedures. Ten patients without embryo transfer (ET) were used as controls. The luteal estradiol, progesterone, and human chorionic gonadotropin were measured by radioimmunoassay (RIA). In 31 cases, a transient elevation of hCG occurred after complete serum clearance of exogenous hCG, suggesting that the transient increase in hCG was of embryonic origin. In addition, five patients were found to have prolonged clearance of hCG, which was due not to individual variation in clearance, but to a minimal production of hCG by trophoblastic tissue. These data suggest that implantations occurred in 12.1% of our so-called "nonpregnant" patients. PMID- 3350160 TI - A new in vitro fertilization technique: intravaginal culture. AB - Intravaginal culture (IVC) is a new technique elaborated by the authors for the fertilization and culture of human oocytes. Its principle consists of fertilization and early development of the eggs in a closed, air-free milieu without the addition of CO2. One to five ovocytes are deposited in a tube completely filled with 3 ml of culture medium less than 1 hour after their recovery, with 10,000 to 20,000 spermatozoa per ml previously prepared. The tube is then hermetically closed and it is placed in the maternal vagina and held by a diaphragm for incubation for 44 to 50 hours. After this time, the content of the tube is examined and embryos are transferred to the uterus. In the first 100 consecutive punctures, 22 clinical pregnancies were obtained: 17 deliveries, 3 spontaneous abortions, and 2 tubal pregnancies. Also, a randomized study comparing IVC to in vitro fertilization (IVF) was done (160 cycles) and no statistically different cleavage, transfer, or pregnancy rate was seen between IVC and IVF. By simplifying the laboratory manipulations, this technique decreases the cost of IVF and permits its standardization and diffusion. It creates a psychologic comfort permitting active participation of the mother in this stage of embryo development. Also, the use of this technique may give greater knowledge of human gamete metabolism and of the physiology of reproduction. PMID- 3350161 TI - Partial characterization of a unique growth factor secreted by human Sertoli cells. AB - Human Sertoli cells were grown in a serum-free environment, and the Sertoli cell conditioned medium (hSCCM) was tested for mitogenic activity. The presence of a potent growth factor(s), termed Sertoli cell secreted growth factor (SCSGF), in hSCCM was confirmed and supports previous observations based on experiments using rat SCCM. Mitogenicity of hSCSGF was demonstrated in cell proliferation assays with the A431 (human epidermoid carcinoma) cell line and in [methyl-3H]-thymidine incorporation (DNA synthesis) assays with the Swiss 3T3 (mouse embryo fibroblast) cell line. In a dose-dependent manner, hSCSGF stimulated A431 cell growth up to 4 fold over control values (P less than 0.0001) and stimulated thymidine incorporation up to 4.5-fold over control values (P less than 0.0002). Importantly, SCSGF stimulated A431 proliferation 2-fold over control values (P less than 0.0002) in the presence of 5% serum. With the exception of rat SCSGF, human SCSGF is the only growth factor known to stimulate A431 cells. SCSGF also demonstrated epidermal growth factor (EGF)-like activity based upon displacement of EGF from its receptor in a radioreceptor assay. However, SCSGF is not EGF since it is a potent stimulator of A431 cells, whereas EGF is inhibitory. The growth factor was stable to heat, freeze-thaw, acid (pH 3), and trypsin treatment. Furthermore, it did not bind heparin agarose and is thus distinct from the endothelial cell growth factor family. High-pressure liquid chromatography on size exclusion (TSK G2000 SW) columns revealed an approximate size of 8000 daltons. Human SCSGF is a unique growth factor and may play a key role in the regulation of normal spermatogenesis. PMID- 3350162 TI - Fluorescent body distribution in spermatozoa in the male with exclusively female offspring. AB - Fluorescent (F) body distribution was determined in a group of men who did not have a fertility problem, but rather had fathered exclusively female offspring. The study was designed to analyze spermatozoa for the frequency of zero F-body (X bearing) and one F-body (Y-bearing) spermatozoa. Semen samples were separated (processed) for Y-bearing spermatozoa enrichment and reanalyzed for fluorescent body distribution. The study consisted of 50 control (10 males) samples (unprocessed), 35 preseparation (35 patients) samples (unprocessed), and 18 postseparation (18 patients) samples (processed). A significantly higher frequency (P less than 0.05) of zero F-body spermatozoa were observed in the preseparation samples when compared with the control samples. The presence of more spermatozoa without fluorescent body correlates with the occurrence of more female births. PMID- 3350163 TI - High potassium concentration improves the rate of acrosome reaction in human spermatozoa. AB - Progressively motile spermatozoa recovered by swim-up method from semen of two fertile men were incubated for 24 hours in culture media containing either 4.7, 15, or 25 mM of potassium (K). Aliquots of each culture condition were obtained at 0, 1, 5, 10, and 24 hours of incubation for the assessment of progressive motility, percentage of dead spermatozoa, and percentage of acrosome reaction (AR), as measured by triple-stain technique. A total of ten experiments including each K concentration were analyzed. The results of this study showed no effect of K concentration on the percentage of progressively motile spermatozoa, irrespective of the time of incubation. The percentage of live spermatozoa was significantly greater in culture medium containing 25 mM K (P less than 0.05). There was a greater percentage of reacted spermatozoa with 25 mM K, as compared with 4.7 and 15 mM (P less than 0.05). Furthermore, the time taken to achieve 20% of AR was 2 hours at 25 mM K compared with 10.9 hours at 4.7 mM K. PMID- 3350164 TI - Concentration of glycerol required for optimal survival and in vitro fertilizing capacity of frozen sperm is dependent on cryopreservation medium. AB - Sperm survival and in vitro fertilizing capacity were examined following cryopreservation with three concentrations of glycerol (0, 2, and 7.5%) and four cryopreservation media. Post-thaw motility and motility index increased with increasing concentrations of glycerol. Post-thaw velocity, linearity, percentage of zona-free hamster oocytes penetrated, and penetrations per oocyte were greater following freezing with 2 or 7.5% glycerol than with 0% glycerol. A significant interaction between media and glycerol was observed for motility, velocity, linearity, motility index, and percentage of oocytes penetrated. These results suggest that the concentration of glycerol required for optimal survival and in vitro fertilizing capacity of human sperm following cryopreservation is dependent on the type of medium used for freezing. PMID- 3350165 TI - The hemizona assay (HZA): development of a diagnostic test for the binding of human spermatozoa to the human hemizona pellucida to predict fertilization potential. AB - The authors present their initial results with the hemizona assay (HZA), which was developed to predict the fertilizing potential of spermatozoa. The HZA uses the matching halves of a human zona pellucida from a nonfertilizable and nonliving oocyte, providing an internal control on zona-to-zona variability. Maximal binding of human sperm to the hemizona usually occurred after 4 to 5 hours of coincubation. Sperm from fertile men exhibited significantly higher binding capacity to hemizonae compared with sperm from men who had fertilization failure during in vitro fertilization (IVF) treatment. The HZA index is calculated as follows: (bound sperm from subfertile male) divided by (bound sperm from fertile male) X 100. These findings demonstrate that the HZA may be a useful diagnostic tool in male infertility evaluations. PMID- 3350166 TI - The use of oral contraceptives to regulate oocyte retrieval. AB - This study was designed to determine the efficacy of using OCs prior to ovulation induction in an IVF-ET program. A total of 26 cycles were initiated after gonadotropin suppression with OCs and 22 laparoscopies (84.6%) were performed. A pregnancy rate of 22.7% per laparoscopy and 23.8% per ET was achieved. The results suggest that the use of OCs to regulate oocyte retrieval can result in acceptable pregnancy rates and facilitate efficient time use of IVF-ET personnel. PMID- 3350167 TI - Survey of attitudes regarding the use of siblings for gamete donation. AB - We conclude that the acceptability of using a sister for gamete donation is high among couples desiring ovum donation. On the contrary, couples undergoing AID generally rejected the concept of using the husband's brother as a known donor. Thus, although similar in concept, disparity exists regarding the use of siblings for gamete donation. Though the use of sibling gamete donation may provide a short-term solution to the dwindling supply of acceptable gamete donors, the long term acceptability of such practice remains unknown. PMID- 3350168 TI - Spontaneous recanalization of cornual tubal occlusion following a pregnancy achieved by in vitro fertilization. AB - A patient with bilateral tubal occlusion conceived by IVF and delivered a healthy infant vaginally. Four months postpartum, the patient again conceived spontaneously and carried to term. Recanalization of one fallopian tube was demonstrated on HSG performed after delivery of the second infant. Mechanical stretching and pregnancy-induced hormonal changes may explain spontaneous recanalization of obstructed fallopian tubes. PMID- 3350169 TI - Pelvic infection after transvaginal ultrasound-guided ovum retrieval. PMID- 3350170 TI - Videomicrographic analysis of the effects of antihuman relaxin antibody on human sperm motility. PMID- 3350171 TI - An evaluation of a commercially available assay for the detection of antisperm antibodies. PMID- 3350172 TI - Pregnancy rates following intrauterine insemination with washed or unwashed sperm. PMID- 3350173 TI - Effect of the family visit on the patient's mental status. PMID- 3350174 TI - Implementation of electrocardiographic monitoring in labor and delivery. PMID- 3350176 TI - You made a difference. PMID- 3350175 TI - Viral myocarditis. PMID- 3350177 TI - Communication problems: how to deal with verbal and telephone prescriptions. PMID- 3350178 TI - Twelve common barriers and misconceptions for the Registered Nurse returning to school. PMID- 3350180 TI - LVNs in critical care area. PMID- 3350179 TI - Two-glove technique. PMID- 3350181 TI - Substitution of surgeon without patient's knowledge. PMID- 3350182 TI - Current management of spontaneous pneumothorax. PMID- 3350183 TI - National Cholesterol Educational Program. PMID- 3350184 TI - Industrial medicine and community doctors. PMID- 3350185 TI - Comparative studies on the structure of biliary immunoglobulins of some avian species. I. Physico-chemical properties of biliary immunoglobulins of chicken, turkey, duck and goose. AB - In pooled bile of chicken, turkey, duck and goose immunoglobulins (Igs)+ were found in relatively high amounts between 4.5 and 15.0 mg/ml (corresponding to 28 to 36% of the total protein contents). All biliary Ig fractions studied possess (H2L2)n structure estimated by SDS-PAGE. In chicken and turkey L chains are assumed to be non-covalently linked to the polymeric H chains. In duck and goose L chains are completely linked to H chains. The Mr of H chains are rather similar: 64 kDa for the Igs of chicken and turkey bile and 67 kDa for the biliary Igs of duck and goose. There are slight differences in the electrophoretic mobility: Chicken and turkey Igs are beta 1/alpha 2-globulins and the corresponding Ig fractions from duck and goose are beta 2-globulins. PMID- 3350186 TI - Effect of increased circulating corticosterone in the immature fowl on the blastogenic responses of peripheral blood lymphocytes. AB - Plasma corticosterone concentrations were increased by giving chickens implants containing corticosterone and the effects on lymphocyte numbers and lymphocyte responses to the mitogens, phytohaemagglutinin (PHA) and concanavalin A (con A), were measured. Raising plasma corticosterone caused a dose-related decrease in numbers of circulating lymphocytes. Blastogenic responses of lymphocytes in whole blood to PHA and con A were reduced and stimulation indices were decreased in those birds with raised circulating corticosterone. When the initial corticosterone-induced lymphocytopenia was taken into account it was evident that corticosterone depressed the responsiveness of the lymphocytes to PHA but not to con A. Additions of corticosterone to cultures of whole blood showed that PHA stimulation was more sensitive than con A stimulation to the inhibitory effects of corticosterone. PMID- 3350187 TI - Effects of propylthiouracil (PTU) on the immunological status of the chicken. AB - Effects of propylthiouracil (PTU) using different treatment schedules on immune functions in young male chicken were studied. Antibody productions to sheep red blood cells (SRBC) and Brucella abortus (BA) were found to rise in the chicks treated with 0.1% and 1% PTU. Furthermore, the chicks treated with 1% PTU exhibited a significantly greater reaction to phytohemagglutinin (PHA) in skin test using the wing web than the control did. Treatment of 5% PTU, however, inhibited the antibody productions to SRBC and BA and the reaction for the skin test to PHA. Antibody titers to both antigens and serum IgG level were lower in the chicks after cessation of PTU treatment. The most conspicuous histology was the lymphatic depletion of the lymphoid organs in chicks treated with 5% PTU. The bursa of Fabricius, thymus and spleen were severely atrophied. The total WBC and the number of lymphocytes and monocytes were significantly reduced in the presence of 0.1% and 1% PTU at 8 weeks of age. Although, concentrations of serum thyroxin (T4) and 3,5,3'-triiodothyronine (T3) were significantly lower in the chicks treated with all doses of PTU, the cessation of the treatment was followed by an increase in the concentrations of serum T4 and T3 to levels not different from in the untreated control chicks. These data showed that PTU at 0.1% and 1% concentrations did not suppress immune responses in chickens unlike the case reported in mammals. PMID- 3350189 TI - Transmission of a sarcoma in the cockle Cerastoderma edule (Bivalvia; Mollusca) using cell transplants. PMID- 3350188 TI - Monoclonal antibody recognized hemocyte subpopulations in juvenile and adult Lymnaea stagnalis: functional characteristics and lectin binding. AB - The mouse monoclonal antibody LS1 recognizes a membrane epitope present on circulating hemocytes of the gastropod mollusc Lymnaea stagnalis. In both juvenile and adult pond snails, LS1+ (LS1 positive) hemocytes have the morphology of immature cells. The percentage of LS1+ hemocytes is higher in juveniles (ca. 39%) than it is in adults (ca. 14%). Functional characteristics of LS1+ hemocytes and lectin binding to these cells were studied. In both age groups, the proliferative activity, as measured by the incorporation of deoxybromouridine, is much higher for LS1+ hemocytes than it is for LS1- (LS1 negative) cells. LS1+ hemocytes are phagocytically less active and have a lower lysosomal enzyme (peroxidase) content as compared to hemocytes that lack the epitope. Histochemical staining of the total population of circulating hemocytes shows that the lectins DBA, BS-l-A4 and BS-l-B4, PNA, SBA and ECA do not react with the hemocytes. LTA, APA, WGA, Con A and LCA bind to all hemocytes. RCA and STA recognize surface carbohydrate moieties present on subpopulations of hemocytes only. The LS1+ hemocyte population virtually lacks the carbohydrate residues recognized by STA, whereas the LS1- population never shows binding of RCA. Our results support the findings that the LS1 epitope is a membrane marker of less differentiated hemocytes in both juvenile and adult L. stagnalis. Furthermore, they suggest a correlation between the presence of the LS1 epitope and the absence of STA binding, whereas absence of the LS1 marker may correlate with the presence of a sugar recognized by RCA. PMID- 3350190 TI - Proliferative and cytotoxic responses of healthy bicolor damselfish. PMID- 3350191 TI - A galactose specific agglutinin from the hemolymph of the snail Achatina fulica: purification and characterization. AB - A galactose specific agglutinin has been detected in the hemolymph of the snail Achatina fulica fulica Bowdich. The agglutinin, which agglutinates rabbit erythrocytes, has been purified by affinity chromatography on crosslinked guargum followed by gel filtration on a Biogel P-200 column. The purified agglutinin has a native molecular weight of 210,000 and comprises of non covalently linked identical subunits of molecular weight 15,000. The pI of the agglutinin was found to be 8.1. The activity of the agglutinin is independent of divalent cations. The inhibition of hemagglutination data reveals that 2-deoxy-D-galactose is the most potent inhibitor of the agglutinin followed by galactose and lactose. PMID- 3350192 TI - In vitro binding of parasites (Bonamia ostreae) and latex particles by hemocytes of susceptible and insusceptible oysters. AB - Bonamia ostreae is a protozoan parasite that has caused severe losses in the flat oyster (Ostrea edulis) industry in Europe. The cupped oyster (Crassostrea gigas), recently introduced and cultured in Europe, is not infected by the disease. In vitro tests were conducted to determine whether there was a difference in the ability of hemocytes from each species to recognize and bind inert foreign particles (fluorescent latex beads) and purified, infective B. ostreae. The results indicated no difference in their ability to bind latex beads, but C. gigas were able to bind more B. ostreae than were O. edulis. The relative inability of the O. edulis hemocytes to recognize the parasite is discussed as a possible factor in flat oyster susceptibility. PMID- 3350193 TI - Cutaneous tumor of northern pike, Esox lucius L. II. Expression of surface and cytoplasmic immunoglobulins and alpha-naphthyl acetate esterase by mononuclear cells from lymphoid tissues and tumor. AB - Rabbit anti-pike IgM antibodies showed that up to 95% of mononuclear (MN) cells isolated on Ficoll-Isopaque gradients from peripheral blood, spleen, and head kidney of northern pikes carrying cutaneous tumors were surface (SIg) and cytoplasmic (CIg) immunoglobulin positive by indirect immunofluorescence. On the contrary, rabbit anti-winter flounder IgM antibodies gave totally negative results. Monoclonal anti-carp IgM antibodies stained approximately 40-56% of peripheral blood, splenic, and head kidney MN cells in assays for SIg and CIg. Monoclonal anti-rainbow trout IgM antibodies, however, did not cross-react with pike Ig. A maximum of 5% of MN cells from the tumor were SIg and CIg positive by anti-pike IgM as well as 6% by anti-carp IgM antibodies, and were negative by the other two antibodies even at low dilutions. A majority of cells in the tumor exhibited an intense diffuse staining pattern for alpha-naphthyl acetate esterase (ANAE) which was inhibited by sodium fluoride and was reminiscent of that noted in human monocytes. These findings show that the Aland pike neoplasm is not a B cell tumor or plasmacytoma, but more representative markers are needed to demonstrate whether it is of T lymphocytic or monocytic origin. PMID- 3350194 TI - Immunosuppression of Clarias lazera (Pisces) by a molluscicide. AB - Exposure of C. lazera to sublethal concentrations of the molluscicide, Bayluscide, for a 6-month period induced 14% (0.1 ppm) and 95% (0.3 ppm) mortalities. In addition, there was a depletion of hemopoeitic tissue in the mesonephros and spleen, an increased susceptibility to pathogens and appearance of nodules containing infectious organisms. Surviving fish produced lower titers of antibodies against injected antigens than controls and the number of corpuscles of Stannius increased in proportion to the concentration and duration of exposure to the Bayluscide. Long term exposure probably induced immunosuppression in C. lazera which caused these changes. PMID- 3350195 TI - Protein/creatinine ratio in the assessment of proteinuria during pregnancy. AB - Since the nature and the level of urinary protein excretion have considerable clinical implications in the course of pregnancy, the early detection of even minor degrees of hyperproteinuria is important. Quantitation of 24-h urinary protein excretion is the only definite method of establishing the presence of hyperproteinuria, but this method shows practical failures particularly in an outpatient setting. Dipstick analysis as a screening for hyperproteinuria also lacks reliability, since the normal rate of protein excretion in primigravid pregnancy has recently been shown to be less that 150 mg per day. In this study, therefore, we propose the determination of the protein/creatinine ratio in a single voided urine sample, obtained during normal daylight activity, as a screening test for hyperproteinuria during pregnancy which can replace the quantitation of 24-h urinary protein excretion. PMID- 3350196 TI - Urinary excretion rates of calcium and magnesium in normal and complicated pregnancies. AB - In this cross-sectional study calcium and magnesium metabolism was investigated in normal pregnancies (n = 34) and pregnancies complicated by either fetal growth retardation of hypertension with or without fetal growth retardation (SGA newborns) (n = 30). Special attention has been given to the renal excretion rates of calcium and magnesium and their relationship to creatinine and sodium clearances. No differences were noted in the third trimester of pregnancy between the normal and complicated pregnancies in calcium or magnesium metabolism except for an increased serum magnesium in the SGA group. Comparing the post-partum period to normal pregnancy the following results were observed: (i) serum ionic calcium levels showed no differences; (ii) urinary calcium excretion was increased as a result of increased calcium clearance. A striking feature was the fact that the fractional calcium clearance was not increased, in contrast to the increase in relative calcium clearance. The observed results can be explained by an increased GFR and a possible dissociation between the sodium and calcium handling in the cortical thick ascending Limb of Henle's Loop. PMID- 3350197 TI - Technique for locating the start of the ovarian cycle in women who have no uterus. AB - A technique was required to identify the start of the ovarian cycle in hysterectomized women. Daily observations of the excretion of pregnanediol relative to creatinine by menstruant women during the course of 15 ovulatory cycles have been used to establish (a) that the centre of the pregnanediol peak can be located from as few as two pregnanediol measurements per week and (b) that this centre precedes the start of menstruation by 7.14 +/- 0.07 days (mean +/- SEM). With this information the onset of menstrual bleeding in an ovulatory cycle can be predicted. Comparison of the prediction with the observation of menstrual onset in 50 cycles gave a mean deviation of 0.276 +/- 0.109 days with a maximum deviation of 1.9 days. In three women observed before and after hysterectomy there was no significant change in the length of the ovarian cycle. It is concluded that this procedure provides a way of identifying the start of a new ovarian cycle in women who have no uterus. The procedure is only applicable to ovulatory cycles. PMID- 3350198 TI - Post-partum isolated ovarian abscess in an asplenic host. AB - A 23-yr-old splenectomized female developed an isolated ovarian abscess, a very rare complication, following a normal delivery. Apart from the palpated 'cyst', findings on pelvic examination were unremarkable, as is often the case with ovarian abscess. The patient recovered after conservative 'cystectomy'. We suggest that the asplenic state plays a role in the development of this very rare complication. PMID- 3350199 TI - Puerperal inversion of the uterus. AB - Puerperal inversion of the uterus is a complication of the third stage of labor. The two main reasons are excessive cord traction and Crede fundal pressure. Its frequency in Israel is unknown. A case of acute, complete inversion of the uterus is presented, treated promptly by immediate reposition and manual separation of the placenta. The various modes of treatment are discussed. Puerperal inversion is a rare and dangerous complication. Prompt diagnosis and the proper choice of treatment will decrease the morbidity and mortality associated with this complication. PMID- 3350200 TI - Regulation of glucocorticoid receptors in the kidney of immature and mature male rats. AB - 1. Specific binding of [3H]dexamethasone to cytosol and the activation of bound hormone-receptor complexes were studied in the kidney of immature (3-week) and mature (26-week) Long-Evans male rats. 2. The concentration of specific binding sites was significantly higher (25%) in the kidney of immature rats as compared with mature, while dissociation constants (Kd) remain unaltered at both ages. 3. Heat activation (25 degrees C for 45 min) significantly enhanced the binding of [3H]dexamethasone-receptor complexes to DNA-cellulose and purified nuclei at both ages to the same extent. Cross-mixing experiments (i.e. binding of activated cytosol from mature rats to nuclei of immature and vice versa) gave similar results to the non-mixed groups. 4. Ca2+ activation (0 degree C for 45 min with 20 mM Ca2+) also enhanced the nuclear and DNA-cellulose binding at both ages but to a greater magnitude in immature rats. 5. Differences in the number of specific binding sites and some of the physicochemical properties of kidney glucocorticoid receptors presented here between immature and mature rats may underlie the functional changes in tissue response with age. PMID- 3350201 TI - Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid (TDGA) on glucose and fatty acid oxidation in isolated rat soleus muscle. AB - 1. The effect of 2-tetradecylglycidic acid (TDGA), a potent, specific inhibitor of long-chain fatty acid oxidation, on fatty acid and glucose oxidation by isolated rat soleus muscle was studied. 2. TDGA inhibited [1-14C]palmitate oxidation by soleus muscle in a concentration-dependent manner. 3. TDGA inhibited the activity of soleus muscle mitochondrial carnitine palmitoyltransferase A (CPT A). 4. Added palmitate (0.5 mM) significantly inhibited D-[U-14C]glucose oxidation and, under conditions where TDGA inhibited palmitate oxidation, the oxidation of D-[U-14C]glucose by isolated soleus muscle was significantly stimulated. 5. TDGA stimulation of glucose oxidation was reversed by octanoate, a medium-chain fatty acid whose oxidation is not inhibited by TDGA. 6. When nondiabetic rats were treated with TDGA (10 mg/kg p.o./day x 3 days), fasting plasma glucose was significantly lowered and the ability of isolated contralateral soleus muscles to oxidize palmitate was inhibited while glucose oxidation was significantly stimulated. PMID- 3350202 TI - Interrelationship between nuclear histone binding and cell proliferation. AB - 1. Binding of non-enzymatically [methyl-14C]-labeled histone H3 to nuclei isolated from young and old rat livers, regenerating rat liver, and tumor cells has been investigated. 2. Scatchard plot analysis indicated that various cell types had different binding capacity and different dissociation constant (Kd). 3. Nuclei isolated from younger rats had fewer binding sites and lower Kd (or higher Ka) values for [methyl-14C]H3 than those from older rats. 4. Fewer binding sites and lower Kd values were also observed with nuclei isolated from the maximally regenerating liver (24 hr after partial hepatectomy) and the fast-growing ascites tumor and Novikoff hepatomas. 5. These results strongly suggest that the number of binding sites and affinity of histone H3 for nuclei appears to be correlated with the degree of cell proliferation. 6. Fractionation of the [methyl-14C]H3 bound nuclei into nuclear membrane and nucleoplasm demonstrates that approx. 94% of radioactivity is associated with the former in which less than 6% of DNA is found, whereas 94% of total DNA is found in nucleoplasm. 7. This suggests that the binding of [methyl-14C]H3 to nuclei is independent of DNA present in each fraction. PMID- 3350203 TI - Platelet deposition on human atherosclerotic lesions is decreased by low-dose aspirin in combination with dipyridamole. AB - Eighteen patients with ischaemic peripheral vascular disease were treated for a 5 week period with either 20 mg aspirin daily, 75 mg dipyridamole three times daily or a combination of these two treatments. Before and after 4 weeks' treatment autologous platelet labelling with 111In was carried out and sites of active vascular platelet uptake monitored, and platelet half-life measured. Neither aspirin nor dipyridamole alone had any effect on platelet uptake or on platelet half-life. The combination of aspirin and dipyridamole resulted in a significant decrease in platelet uptake and a nonsignificant trend towards prolongation of platelet half-life. These findings suggest that this combined therapy may be of benefit in the treatment of atherosclerosis in man. PMID- 3350204 TI - Bioavailability of three commercial preparations of ibuprofen 600 mg. AB - The pharmacokinetic variables of ibuprofen 600 mg were investigated after administration of Brufen and compared to administration of Burana and Ibumetin. The investigation was carried out as a randomized single-dose crossover study in 17 healthy volunteers. The mean maximum plasma concentrations of ibuprofen were 58, 45 and 54 micrograms/ml after administration of Brufen, Burana and Ibumetin, respectively, the time to reach this being 1.4, 2.1 and 1.6 h, respectively, after administration. The differences between Brufen and Burana were significant. The relative bioavailability was very similar between Brufen and Burana but about 8% lower for Ibumetin and this difference between Brufen and Ibumetin was significant. Thus, different brands of ibuprofen may not be pharmacokinetically interchangeable and the results show that Brufen is superior to either Burana or Ibumetin when considering both the rate and extent of absorption. These findings are clinically interesting since a high and early plasma concentration of ibuprofen seems to be related to increased analgesic efficacy. PMID- 3350205 TI - Brighton sleep survey: a study of sleep in 20-45-year olds. AB - A total of 2714 people, aged 20-45 years from the Brighton area who completed a questionnaire were interviewed on their sleep patterns and complaints, medication, behavioural aids, and consumption of caffeine and alcohol. Analysis showed that 24% had delayed sleep onset, 23% awakened frequently, 19% awakened early, 21% were dissatisfied with sleep, and 8% took medication to aid sleep. Of those on night shifts, 29% awakened frequently and 25% awakened early. There were 648 responses describing behavioural sleeping aids. The moderate consumption of caffeine and alcohol had no significant effect on sleep. The main differences between this survey and other published data relate to the comparison of sleep reports from men with those from women, the sleep of nightshift and dayshift workers and the effects of caffeine and alcohol. These differences may arise from sampling characteristics and the form of the questionnaire. PMID- 3350206 TI - Flavoxate hydrochloride for urinary urgency after pelvic radiotherapy: comparison of 600 mg versus 1200 mg daily dosages. AB - This preliminary communication reports on a non-randomized pilot type trial of 34 females with urgency after pelvic radiotherapy who were treated with flavoxate hydrochloride for 4 weeks. A dosage of 600 mg/day was given to 21 patients and 1200 mg/day to 13 patients. Clinically, both regimens achieved comparable results. Urodynamically (first desire volume, bladder capacity and pressure at capacity) treatment with 1200 mg/day was significantly superior to 600 mg/day. Both schedules were equally well tolerated by patients and no treatment interruption occurred. A randomized double-blind trial comparing 600 and 1200 mg/day flavoxate hydrochloride is currently underway the results of which will be reported in due course. PMID- 3350207 TI - Dorsal and ventral cells of cleavage-stage Xenopus embryos show the same ability to induce notochord and somite formation. AB - Cells in the dorsal marginal zone of the amphibian embryo acquire the potential for mesoderm formation during the first few hours following fertilization. An examination of those early cell interactions may therefore provide insight on the mechanisms important for organization of axial structures. The formation of mesoderm (notochord, somites, and pronephros) was studied by combining blastomeres from the animal pole region of Xenopus embryos (32- to 512-cell stages) with blastomeres from different regions of the vegetal hemisphere. The frequency of notochord and somite development was similar in combinations made with dorsal or ventral blastomeres, or with both. Our results show that during early cleavage stages the ventral half of the vegetal hemisphere has the potential to organize axial structures, a property previously believed to be limited to the dorsal region. PMID- 3350208 TI - The relationships between early ionic events, the pattern of protein synthesis, and oocyte activation in the surf clam, Spisula solidissima. AB - The ionic events linked to activation of surf clam (Spisula solidissima) oocytes include a transient increased Ca2+ influx and an acid release. The aim of the present work was to further elucidate the respective roles of these two ionic events and to clarify the possible role of protein kinase C in the sequence of events leading to oocyte activation. K+-enriched seawater, ammonium chloride, and the phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA), a protein kinase C activator, were tested for their ability to promote germinal vesicle breakdown (GVBD), an acid release, increased 45Ca2+ uptake, and a shift in the pattern of protein synthesis. Oocytes activated by addition of K+ ions release an amount of H+ similar to that induced by fertilization, with the same time course, show an increased, verapamil-sensitive, 45Ca2+ uptake that is proportional to the amount of added K+, and undergo a shift in their pattern of protein synthesis, which requires the presence of external Ca2+. Ammonium chloride, at concentrations causing a higher production of acid than that induced by K+ ions or fertilization, does not trigger GVBD nor any increased 45Ca2+ uptake or any detectable shift in the pattern of protein synthesis. Combined additions of ammonium chloride with subthreshold concentrations of K+ ions allow GVBD to occur, thus revealing a synergistic effect of ammonia and K+ ions. TPA slowly induces GVBD, an Na+-dependent acid release, and a shift in the pattern of protein synthesis, in the absence of increased 45Ca2+ uptake. Our results lead us to propose the following sequence of events for the activation of Spisula oocytes: an increased Ca2+ influx contributes to activate protein kinase C which causes a Na+-dependent acid release leading to a rise of pHi. This rise of pHi, although insufficient by itself, may set the pHi in a permissive range for activation to occur through the action of other protein kinase C-sensitive events leading to the production of meiosis-inducing proteins. PMID- 3350209 TI - Regulation of meiotic metaphase by a cytoplasmic maturation-promoting factor during mouse oocyte maturation. AB - During mouse oocyte maturation the regulation of the activity of a cytoplasmic maturation-promoting factor (MPF) was examined. The mouse MPF activity was determined based on its ability to induce maturation in immature starfish oocytes after microinjection with the cytoplasm from mouse oocytes. MPF appeared initially at germinal vesicle breakdown (GVBD), and its activity fluctuated in exact correspondence with meiotic cycles, reaching a peak at each metaphase and almost disappearing at the time of emission of the first polar body. Cycloheximide affected neither the initial MPF appearance nor GVBD. Thereafter, however, in the presence of cycloheximide the meiotic spindle was not formed and MPF disappeared, although the chromosomes remained condensed. After removing cycloheximide, MPF reappeared and was followed by the first metaphase and subsequently by polar body emission. Finally the meiotic cycle progressed to the second metaphase. Thus, for the appearance of MPF, there is a critical period shortly before the first metaphase, after which protein synthesis is required. In the presence of either cytochalasin D or colcemid, MPF activity remained at elevated levels. Addition of cycloheximide to such cytochalasin-treated oocytes, in which the meiotic cycle was arrested at the first metaphase, caused the MPF levels to decrease and was followed by movement of chromosomes to both poles where they decondensed and two nucleus-like structures were formed. Thus, the disappearance of MPF may initiate the metaphase-anaphase transition. Furthermore, detailed cytological examination revealed that chromosomes in cytochalasin treated oocytes were monovalent while those treated only with cycloheximide were divalent, suggesting that dissociation of the synapsis is a prerequisite for chromosome decondensation after the disappearance of MPF. In all these respects, MPF seems to be a metaphase-promoting factor rather than just a maturation promoting factor. PMID- 3350210 TI - Hemidesmosomes and anchoring fibril collagen appear synchronously during development and wound healing. AB - Bullous pemphigoid antisera and monoclonal antibodies to type VII collagen were used to localize hemidesmosomes and anchoring fibrils, respectively, in tissues of developing eyes and healing corneal wounds of New Zealand white rabbits. In the 17-day fetal rabbit eye, both antibodies colocalize to the epithelial-stromal junction of the lid and conjunctival region, but neither binds to the cornea, and electron microscopy demonstrates hemidesmosomes only where the antibodies bind. By 20 days of fetal development, the antibodies colocalize in cornea, and, by electron microscopy, hemidesmosomes are shown to be present as well. In healing 7 mm corneal wounds, both antibodies colocalize at the wound periphery within 66 h. By electron microscopy, hemidesmosomes along small segments of basal lamina are also shown to be present at the wound periphery at this time. These demonstrations of the synchronous assembly of hemidesmosomes and anchoring fibrils support the hypothesis of linkage of hemidesmosomes through the basement membrane to anchoring fibrils. PMID- 3350211 TI - Genetic analysis of developmental mechanisms in hydra. XVIII. Mechanism for elimination of the interstitial cell lineage in the mutant strain Sf-1. AB - The interstitial cell lineage in mutant strain sf-1 of hydra is temperature sensitive and is lost rapidly from tissue when the animal is cultured at a restrictive temperature of 23 degrees C or higher. The mechanism responsible for this cell elimination process was investigated. Sf-1 polyps were treated at a restrictive temperature of 27 degrees C for varying lengths of time, their tissues were macerated, and the resultant dissociated cells were examined for evidence of phagocytosis after Feulgen staining. It was found that large phagocytic vacuoles were present in the cytoplasm of some epithelial cells. These vacuoles contained partially degraded cells, whose nuclei had highly-condensed and intensely Feulgen-positive chromatin granules. This indicated that, as in colchicine-treated (Campbell, 1976) or starved (Bosch and David, 1984) wild-type hydra, the epithelial cells in strain sf-1 engulfed and disintegrated other cells in the phagocytic vacuoles. The incidence of phagocytosis was higher in sf-1 tissue maintained at elevated temperature than in sf-1 tissue maintained at normal temperature. However, the observed incidence was relatively low (maximally 0.14 phagocytosed cells per epithelial cell) and appeared to be too low to account for the very rapid interstitial cell loss occurring in this strain. We concluded that elimination of the interstitial cell lineage at a restrictive temperature in strain sf-1 takes place in part by phagocytosis and in part by other yet-unidentified mechanisms (cf., Marcum et al., 1980). PMID- 3350213 TI - Discontinuities of pattern and rules for regeneration in limbs of crayfish. AB - The most caudal limb in crayfish, the uropod, has two rami, the exopodite and the endopodite. Results of earlier experiments (J.E. Mittenthal et al. (1985) W. Roux's Arch. Dev. Biol. 194, 121-130) indicated that ramus morphogenetic fields in the two rami are equivalent and tandem. Thus the proximal (inner) junction of the rami, where intersegmental membrane separates them from each other and from the coxa, is analogous to a boundary between segments of the body or of a leg. In this region a discontinuity in the positional information carried by the ramus fields might occur. To characterize the morphogenetic fields in the region near this junction we have exchanged the medial and lateral margins of the two rami, performing the four possible grafting operations of this kind. While an experimentally generated discontinuity between the lateral margin of the exopodite and the medial margin of the endopodite (outer-to-outer junction) triggers intercalation of supernumerary rami, a discontinuity of pattern between the medial margin of the exopodite and the lateral margin of the endopodite (inner-to-inner junction) is stable despite the absence of intervening intersegmental membrane. Where intercalation does occur, it can proceed in either direction along the margin of a supernumerary ramus. These results suggest that there is no discontinuity of positional value at the boundary between the rami. The results of all of our experiments on the uropod indicate that a conjunction of separate proximodistal, dorsoventral, and mediolateral component fields may give positional information for generating the uropod. Intercalation restores the continuity of pattern in the proximodistal field. In the mediolateral field a discontinuity of pattern may result from a preferred polarity of intercalation: Outer cells may be competent to generate inner cells, but not vice versa. According to this hypothesis the two rami have tandem ramus fields but mirror symmetric polarity of competence. Alternatively, intercalation may eliminate a mediolateral discontinuity only if the mismatch of mediolateral positional values at the discontinuity exceeds a threshold. The threshold criterion may be a weighted sum of limb field and ramus field positional values. PMID- 3350212 TI - Mutants of Caenorhabditis elegans that form dauer-like larvae. AB - The development, ultrastructure, and genetics of two mutants that form dauer-like larvae have been characterized. Dauer larva morphogenesis is initiated regardless of environmental stimuli, and it is incomplete or abnormal. The resistance to detergent characteristic of normal dauer larvae is not fully achieved, and the mutants are unable to exit from the dauer-like state of developmental arrest. Mutant life span is not extended beyond the three weeks characteristic of the nondauer life cycle, whereas normal dauer larvae can live for several months. Growth of daf-15(m81)IV, the less dauer-like of the two, is nearly arrested at the second (dauer-specific) molt, but feeding is not completely suppressed. Head shape, cuticle, and intestinal ultrastructure are nondauer, whereas sensory structures (amphid and deirid) and excretory gland morphology are intermediate between that of dauer and nondauer stages. The daf-9(e1406)X mutant is dauer-like in head shape, cuticle, and deirid ultrastructure, intermediate in amphid and inner labial neuron morphology, and nondauer or abnormal in the intestine. Also, the daf-9 mutant exhibits abnormalities in the pharyngeal arcade cell processes and pharyngeal g1 gland. Double mutants carrying both daf-9 and daf-15 are more resistant to detergent than either single mutant. Like the single mutants, they cannot complete morphogenesis, and they are unable to exit from the dauer-like stage. Both daf-9 and daf-15 mutations are epistatic to previously described dauer-defective mutations, indicating that these two genes act late in the pathway leading to the dauer larva. The genetic tests and the mutant ultrastructure suggest that the two genes may affect parallel pathways of morphogenesis. PMID- 3350214 TI - Ectodermal influence on physiological cell death in the posterior necrotic zone of the chick wing bud. AB - The phenomenon of "programmed cell death" in the posterior necrotic zone (PNZ) of the chick wing bud was reexamined. Prospective PNZs (pPNZs) were excised from stage 18-21 donor wings and observed for signs of necrosis in vitro. Cell death was quantified by a chromium-51 release assay. Prospective PNZs from the youngest donors (stage 18) showed no signs of death above control levels, while necrosis increased in vitro with increasing donor age. Cell death in the PNZ at stage 24 could be inhibited by removing the overlying ridge at stage 20 or 21. These results suggest that cell death in the PNZ is not rigidly determined early in development as previous studies suggest, but remains responsive to the cellular environment until shortly before the cells die. PMID- 3350215 TI - Skin sensory innervation patterns in embryonic chick hindlimbs deprived of motoneurons. AB - During normal development and following a variety of experimental manipulations (e.g., neural tube rotations, limb shifts), sensory neurons in the chick grow to their correct targets. L. Landmesser and M. G. Honig (1986, Dev. Biol. 118, 511 531) have suggested that sensory innervation may be precise, not because sensory neurons respond to limb-derived guidance cues, but because sensory neurons interact with motoneurons, which do respond to such cues. To test this hypothesis for skin sensory neurons, the ventral neural tube, including the motoneuron precursors, was removed from chick embryos prior to sensory axon outgrowth and the resulting patterns of dermatomes and axonal projections were mapped physiologically and anatomically. As reported previously, dorsal root ganglia (DRGs) and cutaneous nerves formed in their usual locations following the early removal of motoneurons, while most muscle nerves and the plexus region were reduced substantially (A. C. Taylor, 1944, J. Exp. Zool. 96, 159-185; L. Landmesser and M. G. Honig, 1986, Dev. Biol. 118, 511-531; G. J. Swanson and J. Lewis, 1986, J. Embryol. Exp. Morphol. 95, 37-52). The patterns of axonal projections and dermatomes were surprisingly, although not entirely, normal. In particular, cutaneous nerves in motoneuron-depleted embryos were derived from the same DRGs in approximately the same proportions as normal. Thus, while motoneurons may play a facilitative role in the development of the segmental pattern of skin sensory innervation, they do not appear to be essential. PMID- 3350216 TI - Expression of the delta-crystallin genes in the embryonic chicken lens. AB - The amounts of lens mRNA derived from the delta 1- and delta 2-crystallin genes of the chicken were determined by primer extension experiments using gene specific synthetic oligonucleotides. The primer extended products were sequenced to establish the identity of the resulting cDNAs. The results indicated that most of the delta-crystallin mRNA in the 14-day-old embryonic lens contained transcripts derived from the delta 1 gene. Importantly, however, about 1-2% of the extended products were derived from delta 2 mRNA. Although not quantitative, the primer extension experiments suggested that the delta 1/delta 2 mRNA ratio may differ in the lens fiber cells during development between 6 days of embryogenesis and 3 weeks after hatching. These data provide the first demonstration for the presence of delta 2-crystallin mRNA in the chicken lens and raise the possibility that the two linked, extremely similar delta-crystallin genes are differentially regulated during development. PMID- 3350217 TI - The effect of somite manipulation on the development of motoneuron projection patterns in the embryonic chick hindlimb. AB - Although the formation of motoneuron projections to individual muscles in the embryonic chick hindlimb has been shown to involve the specific recognition of environmental cues, the source of these cues and their mode of acquisition are not known. I show in the accompanying paper (C. Lance-Jones, 1988, Dev. Biol. 126, 394-407) that there is a correlation between the segmental level of origin of motoneurons and the somitic level of origin of the muscle cells of their targets in the chick hindlimb. These data are compatible with the hypothesis that the developmental basis for specific recognition is a positional one. Motoneurons and myogenic cells may be uniquely labeled in accord with their axial level of origin early in development and subsequently matched on the basis of these labels. To test this hypothesis, I have assessed motoneuron projection patterns in the embryonic chick hindlimb after somitic tissue manipulations. In one series of embryos, somitic mesoderm at levels 26-29 or 27-29 was reversed about the anteroposterior axis prior to myogenic cell migration and axon outgrowth. Since previous studies have shown that cells migrate from the somites in accord with their position and that somites 26-29 populate anterior thigh musculature, this operation will have reversed the somitic level of origin of anterior thigh muscles. Retrograde HRP labeling of projections to anterior thigh muscles at stage (st) 30 and st 35-38 showed that motoneuron projections were largely normal. This finding suggests that limb muscle cells or their source, the somites, do not contain the cues responsible for specific recognition prior to myogenic cell migration and axon outgrowth. To confirm that specific guidance cues were still intact after somitic mesoderm reversal, I also assessed motoneuron projections in embryos where somitic tissue plus adjacent spinal cord segments at levels 26-29 were reversed in a similar manner. Analyses of the distribution of retrogradely labeled motoneurons in reversed cord segments at st 35-36 indicated that motoneuron projections were reversed. This finding suggests that motoneurons have altered their course to project to correct targets despite the altered somitic origin of their targets and, thus, that specific guidance cues were intact. I conclude that if cues governing target or pathway choice are encoded positionally then they must be associated with other embryonic tissues such as the connective tissues or that guidance cues are acquired by myogenic cells after the onset of migration and motoneuron specification. PMID- 3350218 TI - Growth of linear spicules in cultured primary mesenchymal cells of sea urchin embryos is bidirectional. AB - The growth of spicules of the sea urchin embryo was studied in a simple in vitro system in which primary mesenchymal cells attach to the substrata, migrate and fuse via filopodia, and subsequently deposit CaCO3, which in most cases is in the form of linear rods. The use of autoradiographs following 45Ca2+ pulse-chase labeling revealed that in such a system linear spicules that formed had two focal points of growth. Elongation occurred by addition of approximately equivalent amounts of Ca2+ to both ends of each rod. Multiform spicules having variable numbers of elongation sites (tips) also showed a similar pattern of Ca2+ deposition. Thus, the growth of both linear and relatively complex skeletal forms is apparently accomplished by the same basic mechanism. PMID- 3350219 TI - Medial arterial calcification and its association with mortality and complications of diabetes. AB - Medical arterial calcification was studied among 4,553 subjects in a 20-year, longitudinal study of Pima Indians. The prevalence and incidence of medial arterial calcification were highest among men, the elderly, and patients with Type 2 (non-insulin-dependent) diabetes mellitus. Medial arterial calcification was most commonly observed in the feet and appeared to progress proximally. Proportional hazards analysis was used to evaluate risk factors for medial arterial calcification in the feet and to evaluate medial arterial calcification as a risk factor for death and for complications of diabetes. Among diabetic patients, risk factors for medial arterial calcification were impaired vibration perception, long duration of diabetes, and high plasma glucose concentration (p less than 0.01 for each). Among nondiabetic subjects, age, male gender (p less than 0.01 for each), and high serum cholesterol concentration (p = 0.02) were risk factors for medial arterial calcification. Nondiabetic subjects with medial arterial calcification did not have higher mortality rates than subjects without medial arterial calcification (rate ratio = 0.95, 95% confidence interval = 0.7 1.3). Diabetic patients with medial arterial calcification, compared with diabetic patients without medial arterial calcification, had 1.5-fold the mortality rate (95% confidence interval = 1.0-2.1), 5.5-fold the rate of amputations (95% confidence interval = 2.1-14.1), 2.4-fold the rate of proteinuria (95% confidence interval = 1.3-4.5), 1.7-fold the rate of retinopathy (95% confidence interval = 0.98-2.8), and 1.6-fold the rate of coronary artery disease (95% confidence interval = 0.48-5.4). PMID- 3350220 TI - Reduction of plasma 1,5-anhydroglucitol (1-deoxyglucose) concentration in diabetic patients. AB - The plasma concentration of 1,5-anhydro-D-glucitol(AG)(1-deoxyglucose) is known to decrease in diabetic patients. In order to evaluate the usefulness of this polyol as a diabetic marker, we examined the specificity of the plasma AG reduction in various diseases: the plasma AG level was determined in 108 newly diagnosed diabetic patients, 229 normal subjects and 200 patients with various other disorders. The mean plasma AG concentration in diabetes mellitus was 1.9 +/ 1.8 micrograms/ml (mean +/- SD), which was definitely lower than that in healthy subjects and patients with other diseases including some metabolic and hormonal diseases (mean value range: 13.4-28.3 micrograms/ml). Only the "malignancies" group showed statistically different mean values from that in normal subjects; however, these values were much higher than those of diabetic patients. The AG concentration seemed to be relatively low in some severe by uraemic patients, but is likely to be little influenced by the glomerular filtration rate. Upon adjustment for sex and age, AG concentration was not found to be correlated with the degree of obesity in both healthy subjects and diabetic patients. The plasma AG concentration showed a tendency to be higher in healthy males than in healthy females in all age-matched groups; however, statistically significant differences were not seen. Also, no significant influence of age was observed. PMID- 3350221 TI - Physical training and plasma lipids in type 2 (non-insulin-dependent) diabetic patients. PMID- 3350222 TI - Dose-response hearing loss for white noise in the Sprague-Dawley rat. AB - The effect of noise exposure on the inner ear is well documented. However, the sensitivity to noise-induced damage varies with animal species. The purpose of this investigation was to generate a hearing loss dose-response curve for a 20 day white noise exposure in the Sprague-Dawley rat. Eight male rats were exposed to 110, 100, 95 or 85 dB sound pressure level (SPL) for 6 hr/day, 5 days/week for 4 weeks in a sound-attenuated chamber fitted with a bank of overhead speakers. Controls were placed in an identical chamber without speakers. Four weeks after the exposure period ended, brainstem auditory evoked response (BAER) thresholds were recorded in all rats at 32, 16, 8, 4, 2, 1, and 0.5 kHz. Rats were then killed and cochlear tissues were processed for surface preparation. Hair cells were counted. Outer hair cell loss in the organ of Corti was observed in rats exposed to 95, 100, and 110 dB. Summary cytocochleograms were prepared for each rat by graphing the percentage of all hair cells remaining vs the percentage of distance along the basilar membrane as measured from the apex. The summary cytocochleograms were averaged and the area above this curve, corresponding to hair cell loss, was calculated. BAER threshold elevations (dB) were converted into percentage loss overall hearing function. Noise exposure level (dB) and (1) percentage area above the group average summary cytocochleogram and (2) percentage hearing loss were plotted as dose-response curves. Log-probit analysis was used to calculate ED50 noise exposure levels of 117 and 104 dB (SPL), (1), and (2), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350223 TI - Effects of inhaled chromium dioxide dust on rats exposed for two years. AB - Rats were exposed by inhalation to chromium dioxide (CrO2) dust at design concentrations of 0, 0.5 mg/m3 (stabilized and unstabilized, respectively), or 25 mg/m3 (stabilized) for 6 hr/day, 5 days/week for 2 years. No dust-exposure related pathological changes other than lung lesions were observed in all exposed rats. There were no significant differences in pulmonary responses between unstabilized and stabilized CrO2 at the 0.5 mg/m3 exposure level. The lungs showed minute dust deposition in the alveoli adjacent to the alveolar ducts, but maintained an intact general architecture. The pulmonary responses satisfied the biological criteria for a nuisance dust. At 25 mg/m3, dust deposition was sharply confined to the alveoli in the alveolar duct region. Alveolar walls enclosing dust-laden macrophage (dust cell) aggregates were thickened with hyperplastic Type II pneumocytes and slightly collagenized fibrosis. Alveoli adjacent to the terminal bronchioles were lined with bronchiolar epithelium (alveolar bronchiolarization). In addition, lungs showed foamy macrophage response, cholesterol granulomas, alveolar proteinosis, and minute fibrotic pleurisy. These pulmonary lesions occurred predominantly in female rats. Of 108 female rats, 6 developed keratin cysts and 2 had cystic keratinizing squamous cell carcinoma (CKSCC). None of 106 male rats had either a keratin cyst or a CKSCC. The lung tumors developed from metaplastic squamous cells in the areas of alveolar bronchiolarization at the alveolar duct region. The lung tumors were well differentiated and devoid of characteristics of true malignancy. The CKSCC is an experimentally induced, unique tumor type and is different from the type of spontaneous lung tumor seen in man or animals. The relevance to man of this type of lung tumor appears to be negligible. PMID- 3350224 TI - Reducing the number of rabbits in the Draize eye irritancy test: a statistical analysis of 155 studies conducted over 6 years. AB - The Draize eye irritancy test in rabbits has been the focus of recent efforts to reduce the use of live animals in toxicity testing. A suitable alternative is not yet available; therefore, we studied the adequacy of reducing the number of rabbits used per test. Data generated from 6-rabbit eye irritation tests of 155 various materials were used to determine the ability of irritation scores from all possible combinations of 5-, 4-, 3-, or 2-rabbit subsets to predict the Draize score derived from six rabbits. There are 930, 2325, 3100, and 2325 possible combinations of 155 studies for the 5-, 4-, 3-, and 2-rabbit subsets, respectively. We classify materials using a four-level adjectival rating system based on (among other factors) the Draize score. Comparisons indicated that 5-, 4 , 3-, and 2-rabbit scores were in 98, 96, 94, and 91% agreement, respectively, with the classification assigned on the basis of the 6-rabbit score. The correlation coefficients for randomly selected subsets of 5-, 4-, 3-, and 2 rabbit scores versus the Draize score for six rabbits were 0.998, 0.996, 0.992, and 0.984, respectively. This study confirms the findings of an earlier report by De Sousa et al. (1984), and indicates that a high level of accuracy can be obtained with reduced numbers of rabbits per test. PMID- 3350225 TI - Comparative inhalation toxicity of nickel sulfate to F344/N rats and B6C3F1 mice exposed for twelve days. AB - Groups of F344/N rats and B6C3F1 mice were exposed to aerosols of nickel sulfate hexahydrate (NiSO4.6H2O) 6 hr/day for 12 days to determine the short-term inhalation toxicity of this compound. Target exposure concentrations were 60, 30, 15, 7, 3.5, and 0 mg NiSO4.6H2O/m3. Endpoints evaluated included clinical signs, mortality, quantities of Ni in selected tissues, effect on mouse resistance to tumor cells, and pathological changes in tissues of both rats and mice. All mice exposed to 7 mg NiSO4.6H2O/m3 or greater and 10 rats exposed to 15 mg NiSO4.6H2O/m3 or greater died before the termination of exposures. Quantities of Ni remaining in lungs of rats at the end of the exposure were independent of exposure concentration. Lung burdens of Ni in mice were approximately one-half that in lungs of rats. Exposure of female mice to 3.5 mg NiSO4.6H2O/m3 had no effect on resistance to tumor cells as determined by spleen natural killer cell activity. Histopathological changes were seen in tissues of rats and mice exposed to as low as 3.5 mg NiSO4.6H2O/m3. Lesions related to NiSO4.6H2O exposure occurred in lung, nose, and bronchial and mediastinal lymph nodes. Results indicated that exposure of rats and mice to amounts of NiSO4.6H2O aerosols resulting in Ni exposure concentrations only eight times greater than the current threshold limit value for soluble Ni (0.1 mg/m3) for as little as 12 days can cause significant lesions of the respiratory tract. PMID- 3350226 TI - Lack of cage effects on liver tumor incidence in B6C3F1 mice. AB - Twenty-three chemicals evaluated as hepatocarcinogens in B6C3F1 mice by the National Toxicology Program (NTP) and nine showing equivocal liver tumor effects were examined to determine if the occurrence of liver neoplasms was associated with caging, i.e., if there were significant differences in tumor incidence among cages. A total of 79 dosed groups showing increased liver tumor incidence were evaluated. The analysis showed that the number of instances in which liver tumors showed significant cage effects agreed closely with chance expectation. Experimental design protocols now utilized by the NTP (including random assignment of columns of cages to dosed and control groups, periodic rotation of cage location, and individual caging of mice) further reduce the likelihood that factors associated with the housing of the animals could influence tumor incidence. PMID- 3350227 TI - Developmental toxicity evaluation of inhaled 2-ethoxyethanol acetate in Fischer 344 rats and New Zealand white rabbits. AB - Pregnant Fischer 344 rats and New Zealand white rabbits were exposed to 2 ethoxyethanol acetate (EEA; CAS No. 111-15-9) vapor by inhalation on Gestational Days 6 through 15 (rats) or 6 through 18 (rabbits) at concentrations of 0, 50, 100, 200, or 300 ppm, 6 hr/day. The animals were terminated on Gestational Day 21 (rats) or 29 (rabbits) and fetuses were examined for external, visceral, and skeletal malformations and variations. In rabbits, exposure to 100-300 ppm resulted in maternal toxicity: decreased weight gain at 100-300 ppm, clinical signs at 200-300 ppm, alterations in hematology at 100-300 ppm, reduced gravid uterine weight at termination at 200-300 ppm, and elevated absolute liver weight at 300 ppm. Developmental toxicity was observed at 100-300 ppm: an increased incidence of totally resorbed litters at 200-300 ppm, an increase in nonviable fetuses at 300 ppm, and a decrease in viable implants (live fetuses) per litter at 200-300 ppm. The incidence of fetal malformations (external, visceral, and skeletal) was increased at 200-300 ppm. The incidence of total malformations was 100% at 300 ppm and significantly increased at 200 ppm. Reduced fetal ossification was observed at 100-300 ppm. In rats, exposure to 100-300 ppm also resulted in maternal toxicity: reduced weight gain and reduced food consumption at 200-300 ppm and elevated relative liver weight and alterations in hematology at 100-300 ppm. Absolute maternal liver weight was increased at all EEA exposure concentrations; relative liver weight was increased at 100-300 ppm. Developmental toxicity was observed at 100-300 ppm: increased nonviable implantations/litter (300 ppm), reduced fetal body weight/litter (200-300 ppm), and increased incidence of external (300 ppm), visceral, and skeletal (100-300 ppm) variations indicative of toxicity. The incidence of visceral, skeletal, and total malformations was increased at 200-300 ppm. In conclusion, in both species, inhalation exposure to EEA during organogenesis produced maternal toxicity at 100 300 ppm and developmental toxicity at 100-300 ppm, including teratogenicity at 200-300 ppm. At 50 ppm in both species, there was no evidence of maternal or developmental toxicity, including teratogenicity. PMID- 3350228 TI - Comparison of a radioisotopic incorporation method and the mouse ear swelling test (MEST) for contact sensitivity to weak sensitizers. AB - A radioisotopic incorporation assay utilizing [125I]iododeoxyuridine was compared to the standard mouse ear swelling test (MEST) for the strong sensitizers dinitrofluorobenzene and oxazolone, and for the three weak sensitizers ethylenediamine (EDA), glutaraldehyde, and nickel sulfate. Mice were sensitized epicutaneously on the abdomen for 4 consecutive days prior to challenging the left ear with the test agent and the right ear with the vehicle. A comparison of the mean difference between the test and the control ears showed that measuring reactivity 48 hr postchallenge on Day 7 is the most sensitive time period in the radioisotopic incorporation method. Both the isotopic and MEST assays gave positive results with the potent sensitizers, although the response detected by isotopic labeling of emigrating cells was up to 1000-fold greater than that determined by ear swelling measurements. No response was detected to the moderate to weak sensitizer EDA in either assay. Reactivity to glutaraldehyde was not detected by the radioisotopic assay but was minimally responsive and significant by the MEST. The opposite was true for nickel sulfate where minimal but significant reactivity was seen in the isotopic assay but not in the MEST. Although the radioisotopic assay had the advantages of being more quantitative and of having improved sensitivity, it was of no greater value than the MEST for detecting weak sensitizers. It was concluded that the mouse was not a suitable model for routinely detecting reactivity to weak sensitizers regardless of which of the two assays were used. PMID- 3350229 TI - Comparative toxicity and renal distribution of the platinum analogs tetraplatin, CHIP, and cisplatin at equimolar doses in the Fischer 344 rat. AB - Tetraplatin [tetrachloro(dl-trans)1,2-diaminocyclohexane platinum(IV), NSC 363812] is a new anticancer platinum drug analog targeted for clinical development because of its effectiveness against cisplatin-resistant tumor cell lines and its improved formulation. The toxicity of tetraplatin was compared at equimolar doses to that of cisplatin [cis-diamminedichlorophatinum(II)] and CHIP [cis-dichloro,trans-dihydroxybis-isopropylamine platinum(IV), NSC-256927]. Adult male Fischer 344 rats received an iv bolus injection of 6.7, 13.3, 26.7, or 53.3 mumol/kg of one of these drugs in saline and were killed on Day 1, 3, 5, 8, or 15 postinjection for assessment of toxicity with emphasis on evaluation of nephrotoxicity. Rats to be killed on Day 15 were housed in metabolism cages for daily urine collection. Tetraplatin was less nephrotoxic than cisplatin at equimolar doses; CHIP was not nephrotoxic at these doses. Renal platinum contents were similar after all three drugs and did not appear to be related directly to the nephrotoxicity. Nephrotoxicity was detected 4-5 days after 6.7 mumol/kg cisplatin, was localized to the corticomedullary junction, and progressed with time and dose. Tetraplatin-induced alterations of renal function were first observed after 13.4 mumol/kg on Day 4 as an elevation of urine volume (up to 10 fold) and a smaller elevation of urinary glucose excretion. Tetraplatin lesions were localized in the mid- and outer cortex and, even at the highest dose, were less severe than those observed with cisplatin. There were other prominent toxic effects of tetraplatin, such as gastrointestinal toxicity and myelosuppression, which indicate that factors other than comparative nephrotoxicity may impact the clinical potential of this new agent. PMID- 3350230 TI - In vivo biochemical indices of nephrotoxicity of platinum analogs tetraplatin, CHIP, and cisplatin in the Fischer 344 rat. AB - In vivo biochemical indices of nephrotoxicity were investigated in Fischer 344 rats treated with a new platinum analog, tetraplatin [tetrachloro(dl-trans)1,2 diaminocyclohexane platinum(IV), NSC-363812], in comparison with rats receiving equimolar dosages of cisplatin and CHIP [cis-dichloro,trans-dihydroxybis isopropylamine platinum(IV), NSC-256927]. The goals of this study were to assess the comparative nephrotoxicities and to determine which battery of tests might be useful for the assessment of platinum analog-induced nephrotoxicity in future clinical investigations of these drugs. An iv bolus injection of 6.7, 13.3, 26.7, and 53.3 mumol/kg of each drug in saline was administered and assessment of biochemical parameters was conducted for 15 days postinjection. A combination of urinary enzyme and protein excretion rates along with blood urea nitrogen (BUN) determinations was used to assess the nephrotoxicity of these compounds. At equimolar dosages, tetraplatin appeared to be less nephrotoxic than cisplatin, and CHIP was not nephrotoxic. At all dosages tested, cisplatin increased the rate of urinary excretion of protein, lactate dehydrogenase (LDH), and N acetylglucosaminidase (NAG) between Days 1 and 5. Tetraplatin did not affect these parameters until the 13.3 mumol/kg dosage. Cisplatin had little effect on the excretion rates of the brush border enzymes alkaline phosphatase and maltase, whereas tetraplatin caused an initial elevation with delayed onset of peak excretion rates at 8 days postinjection. Changes in BUN were not evident until after the 13.3 mumol/kg dosage of cisplatin and the 26.7 mumol/kg dosage of tetraplatin. BUN was useful for ranking the relative toxicities of the three compounds tested, but was not as sensitive in detecting the onset of injury that correlated with early histopathological changes. Tetraplatin appeared to be less nephrotoxic than cisplatin on an equimolar basis and the specific manifestations of its toxicity were different from those observed with cisplatin. Urinary excretion rates for LDH, NAG, and protein proved to be sensitive indicators of platinum analog-induced nephrotoxicity. These indices, combined with BUN determinations and functional assessments, facilitated comparisons of the nephrotoxicity induced by cisplatin and tetraplatin in rats. PMID- 3350231 TI - Zeranol and estradiol induce similar lesions in the testes and epididymides of the prepubertal beef bull. AB - Testes and epididymides of three groups (N = 4) of 6-month-old crossbred beef bulls implanted with a placebo or 150, 300, and 600 mg of estradiol-17 beta at birth, 2, and 4 months of age, respectively, or 36 mg of zeranol at birth only were examined for histologic changes and development. There was a reduction (p less than 0.01) in paired testicular weight and seminiferous tubular diameter (mean +/- SE) of zeranol- and estradiol-implanted bulls compared with control bulls, 29.0 +/- 1.3, 20.6 +/- 1.8 vs 48.1 +/- 5.9 g and 70.9 +/- 0.6, 73.7 +/- 1.2 vs 125.9 +/- 2.0 microns, respectively. The basement membranes of seminiferous tubules (mean +/- SE) were thicker in zeranol-implanted bulls (3.34 +/- 0.07 microns) than those in estradiol-implanted bulls (2.74 +/- 0.06 microns), both of which were thicker than those of control bulls (1.05 +/- 0.03 micron) (p less than 0.01). Supporting cells lining the basement membranes in zeranol- and estradiol-implanted bulls were predominantly undifferentiated whereas most supporting cells had differentiated into Sertoli cells in control bulls. Interstitial cells typical of adult Leydig cells and germinal cells in advanced stages of differentiation were abundant in control bulls, but scarce in both zeranol- and estradiol-implanted bulls. The epididymal epithelium was poorly differentiated, lacked microvilli, and was dysplastic, especially in the cauda epididymidis, in both zeranol- and estradiol-implanted bulls. The epithelium was lower in height (p less than 0.01) in both the caput and cauda epididymidis of treated animals than in that of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350232 TI - Effect of inhaled propylene oxide on reproductive parameters in Fischer 344 rats. AB - Reproductive parameters in Fischer 344 rats were evaluated following inhalation of propylene oxide (PO) for two successive generations. Thirty male and 30 female rats were exposed to 0, 30, 100, or 300 ppm PO for 6 hr/day, 5 days/week for 14 weeks and then mated to produce the f1 litters. After weaning, 30 randomly selected f1 pups/sex/group were exposed to PO for 17 weeks and subsequently mated to produce the f2 litters. Reproductive parameters examined included fertility, litter size and neonatal growth, and survival. All adults and selected weanlings were examined for gross and histologic lesions. Toxicity due to PO was demonstrated by decreased body weights of parental f0 and f1 rats at 300 ppm. No treatment-related effects on fertility (mating or conception) were observed in either f0 or f1 matings. Neonatal survival indices for f1 or f2 litters revealed no treatment-related effects. Litter size was decreased in the f1 rats exposed to 100 ppm PO. However, the litter size in the 300 ppm group was comparable to the control group, and no effect on litter size was shown in PO-exposed f2 litters. Pup weights were unaffected by parental exposure to PO in either generation. Pathologic examination of adults and weanlings revealed no changes considered due to PO. Based on these results, it is concluded that inhalation exposure to PO at levels up to 300 ppm over two generations did not produce any adverse effects on reproductive function. PMID- 3350233 TI - Noninvasive measurement of systemic arterial blood pressure in the conscious beagle dog. AB - The objectives of this study were to evaluate a technique for routine, noninvasive measurement of systemic arterial blood pressure and heart rate (HR) in conscious Beagle dogs for toxicologic research. HR, systolic, diastolic, and mean arterial (MAP) pressures were measured with a DINAMAP research monitor (Model 1255, Critikon, Inc.) as follows: Dogs were restrained in a Harvard dog sling, a neonatal cuff was wrapped around the base of the tail, and blood pressure and HR were determined once a minute. Initially, normal values were obtained, 5-10 trials/session, one to three sessions/day for 15 days in six dogs. The day to day, session to session, and trial variabilities were determined and found to be minimal. The day to day diastolic pressure ranged from 74 +/- 18 to 91 +/- 13 mm Hg, systolic pressure from 125 +/- 25 to 156 +/- 22 mm Hg, MAP from 94 +/- 20 to 113 +/- 15 mm Hg, and HR from 111 +/- 21 to 126 +/- 24 beats/minute (bpm). The effects of various drugs on these parameters were determined. Norepinephrine increased diastolic, systolic, and MAP by 75 to 110 mm Hg and decreased HR by half. Epinephrine increased HR by 20 bpm. Phentolamine decreased diastolic, systolic, and MAP by up to 25 mm Hg. Isoproterenol increased HR by up to 130 bpm and decreased diastolic, systolic, and MAP by 20 mm Hg. In addition, the effect of a classic drug interaction on these parameters was determined. When dogs pretreated with the monoamine oxidase inhibitor tranylcypromine were challenged with tyramine, diastolic, systolic, and MAP pressures were increased, whereas HR was decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350234 TI - Nephrotoxicity of intravenously injected cadmium-metallothionein: critical concentration and tolerance. AB - The nephrotoxicity of Cd-metallothionein (Cd-MT) was examined after iv administration of various dosages to mice. The lowest dosage of Cd-MT that produced renal injury was 0.2 mg Cd/kg. This dosage of Cd-MT resulted in 10 micrograms Cd/g in the kidneys 24 hr after administration. A time-course experiment utilizing a higher (0.3 mg Cd/kg) nephrotoxic dose of Cd-MT demonstrated that the renal Cd concentration at 4 and 12 hr was much higher than the critical concentration, but thereafter decreased to about 10 micrograms Cd/g wet tissue by 24 hr. Thus, Cd in excess of 10 micrograms/g appears to damage the kidney and then distributes to other tissues and/or is excreted into urine. When a total of 0.3, 0.4, and 0.8 mg of Cd/kg as Cd-MT was administered in divided dosages over 4 days, as much as 30 micrograms Cd/g was detected in the kidney but no renal injury was observed. Thus, the critical concentration for producing renal injury after acute administration of Cd-MT is estimated to be approximately 10 micrograms Cd/g wet weight. However, with repeated exposure to Cd-MT, this acute critical concentration can be exceeded without producing renal injury, as tolerance to the nephrotoxic effects of Cd-MT develops. PMID- 3350235 TI - A versatile method for simultaneous analysis of families of curves. AB - We have developed a versatile new approach to the simultaneous analysis of families of curves, which combines the simplicity of empirical methods with several of the advantages of mathematical modeling, including objective comparison of curves and statistical hypothesis testing. The method uses weighted smoothing cubic splines; the degree of smoothing is adjusted automatically to satisfy constraints on curve chape (monotonicity, number of inflection points). By simultaneous analysis of a family of curves, one can extract the shape common to all the curves. Up to four linear scaling parameters are used to match the shape to each curve, and to provide optimal superimposition of the several curves. By applying constraints to these scaling factors, one can test a variety of hypotheses concerning comparisons of curves (e.g., identity, parallelism, or similarity of shape of two or more curves), and thus evaluate the effects of experimental manipulation. By optimal pooling of data one can avoid the need for arbitrary selection of a typical experiment, and can detect subtle but reproducible effects that might otherwise be overlooked. This approach can facilitate the development of an appropriate model. The method has been implemented in a Turbo-Pascal program for IBM-PC compatible microcomputers, and in FORTRAN-77 for the DEC-10 mainframe, and has been utilized successfully in a wide variety of applications. PMID- 3350236 TI - Altered amount and activity of superoxide dismutase in sickle cell anemia. AB - The amount and activity of superoxide dismutase (SOD) (EC 1.15.1.1) were measured in red cells collected from 50 white controls, 101 black controls, 50 patients with sickle hemoglobin (SS Hb), 12 with sickle trait, and 11 with other sickling hemoglobinopathies. Red cells from normal black subjects had more SOD amount and activity than normal whites (1.77 U/mg Hb and 2.96 micrograms/mg Hb vs. 1.47 U/mg Hb and 2.64 micrograms/mg Hb, respectively) or blacks with SS Hb or other sickling hemoglobinopathies. Patients with more severe manifestations of SS Hb had lower levels of SOD activity than those with milder symptoms but had the same amount of enzyme protein. Individuals with sickle trait had amounts and activities of SOD comparable to black controls. An alteration in defense to free radical oxygen may play a role in the severity of symptoms experienced by patients with homozygous sickle cell disease. PMID- 3350238 TI - Federation of American Societies for Experimental Biology. 72nd annual meeting. Las Vegas, Nevada, May 1-5, 1988. Abstracts of papers 1-3785. PMID- 3350239 TI - Federation of American Societies for Experimental Biology. 72nd annual meeting. Las Vegas, Nevada, May 1-5, 1988. Abstracts of papers 3786-7553. PMID- 3350237 TI - Reversibility of acute alcohol cardiac depression: 31P NMR in hamsters. AB - Isolated hamster hearts were perfused with 2% ethanol for 30 min and then reequilibrated with control medium. One group of hamsters was pretreated with verapamil. Another group received diltiazem. Myocardial verapamil levels were 9.5 +/- 0.7 mg/g dry wt; diltiazem levels were 22 +/- 7 mg/g dry wt. Energy metabolites were assessed by using 31P NMR standardized with high-pressure liquid chromatography of freeze-clamped tissue. Intracellular calcium was measured by atomic absorption spectrophotometry, marking the extracellular space with K(CoEDTA). After 30 min of perfusion, untreated hamster hearts showed a 74% decrease in developed pressure, a marked increase in end-diastolic pressure, a decrease of ATP from 9.8 to 8.8 mmol, and an increase of Pi from 6.7 to 9.8 mmol, but no change of phosphocreatine (PCr) or intracellular pH (pHi). Verapamil pretreatment partially prevented cardiac depression during alcohol perfusion. Whereas diltiazem had no protective effect. After reequilibration, developed pressure and oxygen consumption significantly exceeded control values. ATP decreased to 8 mmol; pHi, PCr, and Pi showed no significant change. Verapamil pretreated hearts showed better performance than untreated hearts without change in PCr and Pi, whereas ATP dropped slightly to 8.7 mmol. Thus, functional cardiac depression resulting from acute alcohol exposure is reversible. Increased intracellular calcium levels during alcohol exposure normalized after the removal of alcohol. There was no major change in high-energy phosphates during alcohol exposure or after the removal of alcohol. Verapamil protects the heart from functional depression during alcohol exposure without affecting energy resources. PMID- 3350240 TI - Federation of American Societies for Experimental Biology. 72nd annual meeting. Las Vegas, Nevada, May 1-5, 1988. Abstracts of papers 7554-9037; T1-T9; M1-M170. Indexes of abstracts. PMID- 3350241 TI - Competition of activated protein C and urokinase for a heparin-dependent inhibitor. AB - Human urine contains a hitherto unrecognized heparin-dependent inhibitor of activated protein C (APC) (Mr approximately 50,000) that coelutes from heparin Sepharose together with the only observed peak of urokinase inhibitory activity at a position (0.35 M NaCl) similar to that of plasma protein C (PC) inhibitor. Based on functional assays and immunoblot studies, urokinase and APC compete for this crude inhibitor in the absence or presence of heparin. These results suggest that the same heparin-dependent urinary inhibitor that is immunologically different from several known protease inhibitors is responsible for the observed inhibition of APC and urokinase. In the absence of heparin this inhibitor inhibits APC and urokinase with similar rates, and heparin enhances its inhibitory activity toward both enzymes with more pronounced stimulation of its PC inhibitory activity than its urokinase inhibitory activity. Half-maximal stimulation of inhibition of APC occurs at about 2 mU/ml and maximal stimulation (approximately 10-fold increase of the pseudo-first-order rate constant) at greater than or equal to 50 mU/ml of heparin. This is the first demonstration of competition between APC and urokinase for a heparin-dependent inhibitor. These results may therefore represent a new link between the two major antithrombotic pathways, the PC pathway and the fibrinolytic system. PMID- 3350242 TI - Consequences of stress: a multiplicative function of health status. AB - We hypothesized that an individual's state of health affects its response to stress. To test this, we used the natural history of inherited heart disease in hamsters as a sliding scale of organ vulnerability on which we superimposed a constant set of stressors. When the animal was stressed at an early point in its disease, heart failure did not develop. Later, after cardiac compensatory changes had developed, stress precipitated overt heart failure. Finally, stress administered when the animal was in overt heart failure further amplified the medical consequences of stress, and some animals succumbed. PMID- 3350243 TI - Induction by verapamil of a rapid increase in ATP consumption in multidrug resistant tumor cells. AB - A marked increase in cellular ATP consumption was induced by verapamil in the multidrug-resistant (MDR) cell line 2780AD, but not in the drug-sensitive parental cell line A2780. A group of structurally unrelated drugs in concentrations known to reverse MDR, but not the verapamil analog tiapamil, a weak modulator of MDR, had similar effects. This effect was saturated at verapamil concentrations of about 1 microM. These data demonstrate that verapamil concentrations in MDR cells are maintained at a low level at the expense of ATP hydrolysis, and provide a first indication of the amount of metabolic energy used in this process. PMID- 3350244 TI - Encounter on the airwaves. PMID- 3350245 TI - Ethanol levels in vivo. PMID- 3350246 TI - [Value of x-ray computed tomography in cancer of the esophagus. Prospective and blind study]. AB - Most complementary investigations assessing the resectability of esophageal carcinoma are not very accurate. In approximately half of the patients who undergo surgery, the surgeon discovers unknown growth extension of the tumor. The aim of this study was to define the place of CT scan in the assessment of esophageal cancer. A prospective study concerning 54 cases of squamous cell carcinoma was conducted during 18 months. We consecutively tested the sensitivity and the specificity of information supplied by a CGR 10000 CT scan. The reading was done by the same radiologist who was unaware of the other preoperative findings. All cases of carcinoma were proved histologically. The characteristics of the tumor itself were accurately described by CT scan. Tracheobronchial spread was correctly assessed in 96.2 p. 100 of cases; specificity was 100 p. 100. On the contrary, the sensitivity of the nodal involvement was weak (less than 55 p. 100) for the abdominal as well as the mediastinal areas. Moreover, CT scan identified 48 out of 49 patients without metastases. The results of this study did not allow to determine the value of signs of tumoral spread to the aorta, pericardium, and intra-abdominal regions and therefore CT scan can not be used to determine invasion of the pleural or peritoneal serosa. These results suggest that: a) CT scan alone is not sufficient in the assessment of patients for surgery, b) CT scan facilitates the choice of operative strategy, c) oncologic classification of non operative carcinoma, correct fields of radiation therapy, and follow-up of malignancy through chemotherapy are improved. PMID- 3350247 TI - [Distal constipation, straining at stool and fecal incontinence]. PMID- 3350248 TI - [Biliary lithiasis in cirrhosis: yes, but why?]. PMID- 3350249 TI - [Cirrhosis and biliary lithiasis in France: a postmortem study]. AB - The prevalence of cholelithiasis was estimated in 434 cirrhotic patients and 1582 non cirrhotic patients necropsied at Hopital Beaujon from 1976 to 1984. The overall prevalence of cholelithiasis was significantly higher in cirrhotic than in non cirrhotic patients, 26.3 p. 100 and 20.3 p. 100, respectively. The prevalence of cholelithiasis was higher in cirrhotic than in non cirrhotic patients, whether male or female and at any age, except in women over 60 years and in men over 80 years; in these groups, the prevalence of cholelithiasis in non cirrhotic patients was especially high and therefore did not significantly differ from that in cirrhotic patients. The cause of cirrhosis did not significantly influence the prevalence of cholelithiasis; however, although the number of studied patients was small, the prevalence of cholelithiasis seemed to be particularly high in primary biliary cirrhosis. The prevalence of cholecystectomy was lower in cirrhotic than in non cirrhotic patients, which suggests that cholelithiasis might be less often symptomatic and/or less often complicated in the former than in the latter. PMID- 3350250 TI - [Hepatotoxicity of drugs. Update of a data bank of hepatic involvements and responsible drugs]. PMID- 3350252 TI - [Vascular malformations of the cecum: treatment by embolization. Apropos of 2 cases]. AB - Two cases of arteriovenous malformations of the cecum treated by transcatheter embolization are presented. In both cases, treatment resulted in improvement of the clinical and biological signs. In general, there is a high risk of ischemic complications associated with this treatment. Embolization of arteriovenous malformations should be considered rarely and in the following cases: single lesion, high blood output, feasibility of superselective catheterization. The risk of colonic ischemia calls for preparation of the colon as if the patient were undergoing colonic surgery, as well as thorough clinical follow-up (for at least 10 days). PMID- 3350251 TI - [Terminal constipation caused by abdominopelvic asynchrony: analysis of etiological, clinical, manometric data and therapeutic results after rehabilitation by biofeedback]. AB - The aim of this study was to describe the etiological, clinical, rectoanal manometric findings as well as the results of biofeedback therapy in a series of 65 patients (34 males, 31 females, aged between 5 and 77 years) presenting with severe primary constipation due to pelvic abdominal asynchronism. Pelvic abdominal asynchronism was statistically more frequent in males during childhood and in female patients during adult life (p less than 0.005). This study disclosed a high frequency of psychogenic factors in the onset of pelvic abdominal asynchronism (26 p. 100) as well as a high frequency of soiling (46.2 p. 100) in constipated patients. In 36.2 p. 100 of cases, pelvic abdominal asynchronism was the only abnormality. In contrast, in most of the patients, asynchronism was associated with miscellaneous rectoanal disorders: increased anal closure pressure (43.3 p. 100), decreased anal closure pressure (11.8 p. 100), impaired rectal conscious sensitivity (11.7 p. 100), and increased rectal compliance (31 p. 100). This study demonstrated that when high-fiber diet and laxatives fail, biofeedback therapy is a very interesting alternative, providing 80 p. 100 of good results in selected cases. However, we were unable to find any clinical or manometric parameters predictive of results of treatment. Follow-up studies are needed to determine long-term results of biofeedback training. PMID- 3350253 TI - [Hepatic involvement associated with ingestion of metapramine]. AB - The authors report the cases of 3 women who developed hepatic injury during administration of metapramine, a tricyclic antidepressant introduced in France in 1984. One patient had jaundice and pruritus; the 2 others had loss of weight. Serum alkaline phosphatase and serum transaminase activities were increased in 3 and 2 patients, respectively. Blood hypereosinophilia was found in one patient; erythrocyte sedimentation rate was elevated in 2 patients. The outcome was favorable after drug withdrawal in the 3 patients. Liver biopsy showed centrolobular cholestasis in the 3 patients. There was no rechallenge; in 2 patients, other drugs than metapramine might be implicated in hepatic injury; however, the similarity of these 3 cases suggests that metapramine, like other tricyclic antidepressants, may be responsible for hepatic injury. PMID- 3350254 TI - Usefulness of manometry in colonic inertia. PMID- 3350255 TI - [Constipation: the role of depression is underestimated by gastroenterologists]. PMID- 3350256 TI - [Action of cisapride on the orocecal transit time of a dyspeptogenic meal in healthy subjects]. PMID- 3350257 TI - [Gallbladder lithiasis and cirrhosis: prevalence and risk factors in 150 patients]. PMID- 3350258 TI - [TELHEPAT: a data bank on the hepatotoxicity of drugs accessible by Minitel]. PMID- 3350259 TI - [Acute hepatitis due to piroxicam: a new case]. PMID- 3350260 TI - [Acute benign hepatitis probably due to maprotiline]. PMID- 3350261 TI - [Jaundice caused by compression of the common bile duct: a rare complication of a biliary cyst of the liver]. PMID- 3350262 TI - Barrett's esophagus in scleroderma: increased prevalence and radiographic findings. AB - Ten of 27 patients (37%) with scleroderma who underwent endoscopy at our hospital between 1980 and 1984 for symptoms of reflux esophagitis had biopsy-proven Barrett's esophagus. Two of those 10 patients had esophageal adenocarcinomas. In a blinded review of esophagrams (all but 2 using double-contrast technique) from 16 of the 27 patients, only 1 patient was thought to be at high risk for Barrett's esophagus due to a high esophageal stricture with an adjacent reticular pattern of the mucosa. The latter patient had biopsy-proven Barrett's mucosa. Eight patients were thought to be at moderate risk for Barrett's esophagus due to reflux esophagitis and/or distal strictures in 6 and polypoid intraluminal masses in 2. Three of the 6 patients with esophagitis and/or strictures had Barrett's esophagus, and both patients with masses had adenocarcinomas arising in Barrett's mucosa. Finally, 7 patients who had no esophagitis or strictures were thought to be at low risk for Barrett's esophagus. None of those 7 had histologic evidence of Barrett's mucosa. Thus, the major value of double-contrast esophagography is its ability to classify patients into high-, moderate-, and low-risk for Barrett's esophagus to determine the relative need for endoscopy and biopsy in these patients. PMID- 3350263 TI - Gastric hamartomatous polyp without polyposis coli: radiologic diagnosis. AB - Gastric hamartomatous polyps were found in 25 patients over a period of 4 1/2 years, for an incidence of 11% in all endoscopically biopsied polyps. The number of polyps was fewer than 5 in most patients. All polyps were sessile, sharply demarcated, hemispheric protrusions, measuring up to 10 mm in diameter but most were less than 5 mm. The most characteristic finding differing from hyperplastic polyps, adenoma, and polypoid carcinoma was that hamartomatous polyps were located in the fundic gland mucosa, which was demonstrated as a rugal area on moderately distended double-contrast radiographs. PMID- 3350264 TI - Duodenojejunal intussusception secondary to duodenal tumors. AB - Duodenojejunal intussusception secondary to duodenal tumors is an uncommon entity. The classic coiled-spring appearance, fairly visible in the jejunum, is not apparent in the duodenum due to its fixed position. This explains why the intussusception is located superiorly in the genu inferius and inferiorly in the duodenojejunal junction. This aspect should not be confused with two separated masses. PMID- 3350265 TI - CT findings in left paraduodenal herniae. AB - Computed tomography (CT) was used to evaluate mass effect on the greater curvature of the stomach in two children with histories of intermittent, recurrent vomiting. The paraduodenal herniae were identified on CT in both of these patients as small bowel interposed between the stomach and the body of the pancreas. PMID- 3350266 TI - Pancreatic pseudotumors associated with multifocal idiopathic fibrosclerosis. AB - Two patients with multifocal idiopathic fibrosclerosis and sclerosing cholangitis developed biliary obstruction due to a fibrotic pancreatic pseudotumor. The masslike fibrosis mimicked pancreatic carcinoma on sonography and cholangio pancreatography. In one patient sonography was successfully used to assess the response of the pseudotumor to corticosteroid therapy. PMID- 3350267 TI - Emphysematous cholecystitis: pitfalls in its plain film diagnosis. AB - The clinical and radiographic findings of emphysematous cholecystitis are usually characteristic. However, on occasion the radiographic findings may be simulated by other processes. In such circumstances accurate diagnosis can usually be rapidly established by a variety of simple radiographic maneuvers and procedures. Five illustrative cases are presented herein and the pertinent literature is reviewed. PMID- 3350269 TI - Gastrobronchial fistula: an unusual complication of Nissen fundoplication. AB - Gastrobronchial fistula is a rare complication of antireflux surgery. Presentation can be subacute, with only productive cough. Endoscopy often fails to visualize these fistulae. Barium in the bronchial tree during postoperative upper gastrointestinal series is diagnostic, but can be confused with that appearing due to aspiration. Every case reported after antireflux surgery has followed intrathoracic Nissen fundoplication. PMID- 3350268 TI - Ultrasonically and fluoroscopically guided therapeutic percutaneous catheter drainage of the gallbladder. AB - Percutaneous gallbladder drainage was performed in 16 poor surgical risk patients; 13 had acute cholecystitis, 1 had cholangitis and septicemia, 1 had undergone removal of a gallbladder calculus, and 1 had pancreatic carcinoma with bile duct occlusion. Catheterization and drainage of the gallbladder succeeded primarily in all patients. Catheter dislodgement occurred within 24 h in 1 patient without any side effects. One 87-year-old patient died 14 h after the insertion of the catheter from reasons unrelated to the drainage procedure. Percutaneous removal of gallbladder calculi failed in 3 patients, 2 of whom had been successfully treated for cholecystitis by catheter drainage. Percutaneous gallbladder drainage is a fast, low-risk, inexpensive procedure well suited for the treatment of acute, poor surgical risk patients. PMID- 3350270 TI - Hepatic heterogeneity on CT in Budd-Chiari syndrome: correlation with regional disturbances in portal flow. AB - A comparative study of the imaging findings of computed tomography (CT), selective arteriography, CT arteriography, and/or CT portography is presented in 4 patients with Budd-Chiari syndrome. Hepatic differences in attenuation and morphologic changes were generally found to be closely related with regional disturbances in portal flow. Areas with complete hepatic vein obstruction were hypodense on pre- and postcontrast scans, probably due to portal flow inversion. In 2 of 4 cases, these were subsequently atrophied, while areas receiving the remaining venous outflow appeared hypertrophied. They were markedly enhanced on postcontrast scans. Enhancement may be patchy due to portal and sinusoidal stasis. PMID- 3350271 TI - Association of Meckel's diverticulum and Crohn's disease. AB - A significant association between Meckel's diverticulum and Crohn's disease has been suggested in the clinical literature. Ten patients with entities demonstrated radiographically as well as cases reported in the literature were analyzed to determine the relevance of this association to radiologic evaluation. The Meckel's diverticulum in most cases was an incidental finding whereas the Crohn's disease usually accounted for the patient's clinical symptoms. Recognition of this association should prevent unnecessary laparotomy for an incidental Meckel's diverticulum and improve the radiographic diagnosis of coexistent Crohn's disease. PMID- 3350273 TI - Impact of the barium enema on patient management. AB - The medical records of 214 consecutive inpatients who had a barium enema examination were reviewed, and the clinical indications, efficacy of the barium enema, and patient outcome were correlated to determine the impact of the barium enema on patient management. The most frequent indications were rectal bleeding (33%), abdominal pain (31%), anemia (17%), weight loss (12%), and previous lesions needing reevaluation (12%). Diverticular disease (30%), colonic polyps (10%), and primary or secondary malignancies (12%) were the most common abnormalities detected radiographically. The sensitivity of the barium enema for colonic neoplasms was 89%, with only 1 small cecal polyp being undetected. The effects of barium enema on patient management were serious pathology excluded (64%), diagnosis made that changed therapy (24%), existing therapy continued (10%), and a further study ordered (2%). No serious or life-threatening lesion was missed by barium enema. PMID- 3350272 TI - Evacuation proctography: an investigation of rectal expulsion in 20 subjects without defecatory disturbance. AB - Evacuation proctography is a dynamic investigation of rectal expulsion that records the voluntary evacuation of thick barium paste on videotape. Evacuation is a passive phenomenon in a defined zone of the rectum, associated with pelvic floor descent of 3 cm from a resting position of the anorectal junction less than 2 cm above the plane of the ischial tuberosities. The anal canal does not open immediately; it takes about 4.5 sec to open to a maximum diameter of 1.5 cm, with rectal emptying in 11 sec. Anterior rectoceles commonly invert over the anal canal as the rectum collapses in at the end of evacuation. PMID- 3350274 TI - Anisakiasis confirmed by radiography of the large intestine. AB - As yet, there has been no report of acute anisakiasis of the large intestine diagnosed by radiographic demonstration of the larvae. We present such a case, in which roentgenologic examination revealed Anisakis larvae in the ascending colon. PMID- 3350275 TI - Interventional radiologic treatment of complications following gastric bypass surgery for morbid obesity. AB - Complications of gastric bypass surgery include leakage from the gastrojejunal anastomosis with abscess formation and anastomotic stenosis. Using interventional radiologic techniques, we have treated 18 patients with such complications following surgery for morbid obesity, with clinical success in 11. Procedures included 9 abdominal abscess drainages and 7 balloon dilatations of stenotic or occluded gastrojejunal anastomoses. Eight of 9 abscesses resolved completely; 3 of 7 balloon dilatations resulted in long-term clinical improvement. We describe the techniques used as well as problems encountered in these patients. PMID- 3350276 TI - The effect of omeprazole on ultrastructural changes in gastric parietal cells. AB - This study was designed to compare the effects of omeprazole and cimetidine on ultrastructural changes in parietal cells of guinea pigs during histamine stimulation. Both omeprazole and cimetidine remarkably inhibited acid secretion induced by histamine stimulation. Omeprazole, however, failed to prevent the morphological transition of parietal cells to an active stage during histamine stimulation, in contrast to cimetidine which inhibited the morphological transition. In addition, it was noticed that administration of omeprazole caused vacuolation in approximately 27% of all parietal cells. This phenomenon was not seen in control animals with histamine stimulation alone and only very rarely in cimetidine treated animals. Ultrastructural findings suggested that vacuoles originated in secretory canaliculi of parietal cells. These results may be the key to explain the difference of the inhibitory mechanism between omeprazole which acts on the final step of intracellular process (so-called proton pump) and cimetidine which acts on the H2-receptor site of plasma membrane. PMID- 3350277 TI - Experimental immunological intrahepatic cholestasis model. AB - Heat-killed Propionibacterium acnes (P. acnes) was intravenously injected into tuberculin-sensitized guinea pigs, and 7 days later, purified protein derivative (PPD) was also injected intravenously resulting in marked reductions in bile flow and bile acid excretion. Serum levels of bile acids and cholesterol were increased, and the activities of alkaline phosphatase (ALK-p) and leucine aminopeptidase (LAP) were also elevated. Histological examination revealed dilatation of bile canaliculi and diminution of microvilli. These results indicated that intrahepatic cholestasis was induced. These pathological changes were not detected in guinea pigs in which PPD was not injected. In this experimental model, the tuberculin-sensitized lymphocytes were infiltrated into the liver by P. acnes injection and the cholestatic factor was produced by PPD injection, resulting in the induction of intrahepatic cholestasis. PMID- 3350279 TI - Macroautoradiographic and densitometric studies of [14C]dimethadione in rats: accumulation of the compound in the pancreas. AB - Whole-body autoradiographic and densitometric distribution studies were performed on rats to investigate the accumulation of [14C]dimethadione (DMO) in the pancreas. [14C]DMO was intravenously administered at a dose of 167 microCi/0.5 mg/kg. Animals were sacrificed 1, 15, 30, 60 and 180 min after administration of the radioactive compound. The compound was found to rapidly distribute in all body tissues. The distribution pattern of the compound in the pancreas was spotty or linear due to the presence of the radioactive compound in blood of intrapancreatic vessels and in pancreatic ducts at higher levels than parenchyma. The radioactivity of pancreatic ducts became more evident with time, indicating the gradual accumulation of the compound in the ducts. These findings provide morphological evidence that DMO is accumulated in the pancreas and possibly eliminated from pancreatic juice. Densitometry revealed that the levels of radioactive compound in the pancreas were virtually as high as those in the liver and kidney. PMID- 3350278 TI - Treatment of chronic hepatitis B with recombinant leukocyte interferon and cyanidanol. AB - Twelve male patients with chronic hepatitis B were treated by the combination of recombinant human alpha-interferon and cyanidanol. They received 3 million units of interferon twice a week and 2,250 mg of cyanidanol daily for 24 weeks. Four patients had sustained clinical improvement in which hepatitis B e antigen and DNA polymerase disappeared from sera and aminotransferase activities fell to normal levels. Elevated pretreatment aminotransferases were associated with the response to therapy. Also, decreased number of OKT4-positive cells prior to treatment were observed among responders. Side effects were minimal and all patients tolerated treatment on an outpatient basis. Twice weekly administration of recombinant leukocyte interferon with cyanidanol may be effective in treating chronic hepatitis when patients are appropriately selected. PMID- 3350280 TI - A case of vasculitic cholecystitis associated with Schonlein-Henoch purpura in an adult. AB - A case of Schonlein-Henoch Purpura (SHP) in a 32 year-old female, showing gastrointestinal manifestations including acute vasculitic cholecystitis was reported. In the course of hospitalization urgent laparotomy was performed because of the severe abdominal pain. The gallbladder was inflamed with a brownish-red edematous wall and subserosal hemorrhage, and was resected. Histological examination of the resected gallbladder specimen revealed leucocytoclastic vasculitis. The patient was treated with prednisolone postoperatively, and symptoms abated over two weeks. Acute cholecystitis with SHP is extremely rare, and as far as the authors know this is the second case of this disorder documented by histological examination. Patients with acute abdomen associated with SHP should be managed with consideration of the complications of acute cholecystitis. PMID- 3350281 TI - Omeprazole (20 mg daily) versus cimetidine (1200 mg daily) in duodenal ulcer healing and pain relief. AB - We conducted a double-blind, randomized, parallel group study in 169 patients with acute duodenal ulcers to compare omeprazole, 20 mg daily, with cimetidine, 600 mg twice daily. After 2 wk, 58% of the omeprazole-treated patients and 46% of the cimetidine-treated patients were completely healed (p = 0.056). After 4 and 6 wk 84% and 88% healed with omeprazole, and 80% and 89% healed with cimetidine (p = NS). After 2 wk, pain was completely gone in 62% of the omeprazole-treated patients versus 46% of the cimetidine-treated patients (p = 0.04). Clinical or laboratory adverse events were reported in 6 (7%) of the omeprazole-treated patients and 11 (13%) of the cimetidine-treated patients (p = NS). An adverse event caused withdrawal of 1 patient on omeprazole (anxiety and depression) and 2 patients on cimetidine (diarrhea and fall in hemoglobin). We conclude that omeprazole (20 mg daily) resulted in a trend toward more rapid ulcer healing compared with a relatively high dose of cimetidine (600 mg b.i.d.), and was preferred by patients for relief of ulcer pain. PMID- 3350282 TI - Role of exogenous acid and retransfusion in hemorrhagic shock-induced gastric lesions in the rat. AB - The separate roles of exogenous acid, ischemia, and retransfusion of shed blood on gastric lesion formation in the rat hemorrhagic shock model were studied. In addition, the role of oxyradicals in lesion formation in this model was studied. Intragastric HCl increased gastric mucosal lesion formation in a dose-dependent manner. Even in the absence of intragastric HCl, ischemia followed by retransfusion of shed blood caused histologic mucosal injury in the corpus and antrum. Allopurinol, a xanthine oxidase inhibitor that prevents oxyradical formation, slightly, but significantly, reduced the gastric mucosal injury induced by ischemia-reperfusion but not that induced by ischemia alone. There was no significant difference in the extent of damage caused by ischemia-reperfusion and ischemia alone. We conclude that exogenous acid, ischemia, and oxyradical formation after retransfusion of shed blood are all important interacting factors in the rat hemorrhagic shock model of gastric mucosal injury. Allopurinol, by inhibiting formation of the oxyradical component, significantly protects against the injury. PMID- 3350284 TI - Effect of anger on colon motor and myoelectric activity in irritable bowel syndrome. AB - The present investigation was designed to study the effect of anger on colon motor and myoelectric activity in irritable bowel syndrome. Patients with irritable bowel syndrome were compared with normal controls during resting and two anger stressors: criticism of performance on an intelligence test and during a delay of assistance for a diagnostic procedure. At rest patients with irritable bowel syndrome had higher motor and spike potential activity than normal subjects; however, the difference was only significant for spike activity. Anger significantly increased colon motor and spike potential activity in the groups compared with the resting state. Patients with irritable bowel syndrome produced significantly higher motor and spike potential activity when angered. They also reported themselves to be more hostile and appeared angrier than normal controls after the study. However, they did not report themselves to be more anxious or depressed, suggesting that the observed changes in colonic function of both groups were due to anger. Patients with irritable bowel syndrome scored significantly higher than controls on the Minnesota Multiphasic Personality Inventory scales of hypochondriasis, hysteria, and depression, but these personality factors did not significantly influence their anger level before the study. The results are discussed in terms of the role of learning in the colon and the abnormal reinforcement of bowel behavior in patients with irritable bowel syndrome. PMID- 3350283 TI - Participation of gastric mechanoreceptors and intestinal chemoreceptors in the gastrocolonic response. AB - In this study we investigated the site and nature of the signal responsible for the generation of the gastrocolonic response at the rectosigmoid region. Sixteen healthy subjects participated in this study. Motor activities were recorded with pressure transducers placed in the rectosigmoid colon. Balloon distention of the stomach with 100, 200, or 300 ml of water caused a volume-dependent increase in rectosigmoid motility that was abolished by atropine. To investigate the intestinal phase of the gastrocolonic response, we infused into the duodenum isocaloric (178 kcal) solutions of normal saline, lipid, glucose, or essential amino acids at 1.5 ml/min for 30 min in random order on separate days. Only lipid infusion caused an increase in rectosigmoid pressure and this was accompanied by an elevation of plasma cholecystokinin from 1.2 +/- 0.1 to 4.3 +/- 1.0 fmol/ml. The increase in motility associated with lipid infusion was antagonized (58% +/- 7%) by atropine. To further investigate the possible role of cholecystokinin as a mediator of the gastrocolonic response, we infused cholecystokinin-octapeptide intravenously at doses of 5, 10, and 20 ng/kg.h. A significant increase in rectosigmoid motility was observed only at 20 ng/kg.h and this was accompanied by an increase in plasma cholecystokinin levels to 12 +/- 2 fmol/ml, a value threefold greater than that produced by lipid infusion. These studies demonstrate that gastric distention and intestinal lipid are potent stimuli for the generation of the gastrocolonic response involving the rectosigmoid region. The gastric phase can be generated by mechanoreceptors utilizing the cholinergic pathways, whereas the intestinal phase is nutrient-specific, partially atropine sensitive, and independent of cholecystokinin. PMID- 3350286 TI - Relationship between distention and absorption in rat intestine. I. Effect of luminal volume on the morphology of the absorbing surface. AB - Previous studies in vivo have suggested that distention of the intestinal lumen may enhance intestinal absorption by augmenting absorptive surface area. The precise anatomic mechanism for this increase in surface area, however, has not been explored in detail. We developed methods for rapidly freezing and fixing intestinal segments in situ in the nondistended or distended state. Distention led to a reduction in villus height (309.2 +/- 9.9 to 230.7 +/- 11.8 micron) and a marked increase in the width of intervillus space in both the transverse (50.4 +/- 4.8 to 298.0 +/- 24.8 micron) and longitudinal (15.2 +/- 3.4 to 76.0 +/- 10.6 micron) dimensions. There was, however, no absolute change in total mucosal surface area. The changes in morphology occurred instantaneously, were entirely reversible, and were demonstrated at pressures that occur spontaneously in the mammalian intestine. These studies demonstrate that luminal distention results in marked alterations in intestinal histology that promote increased access of luminal contents to intervillus transport sites in the intestine in vivo. The resulting alterations could lead to an increase in functional rather than absolute absorptive surface area. PMID- 3350285 TI - Biotin transport in basolateral membrane vesicles of human intestine. AB - The characteristics of the exit process of biotin from the enterocyte, i.e., transport across the basolateral membrane, was determined using an enriched basolateral membrane vesicle preparation of human intestine. Purity and suitability of basolateral membrane vesicles for transport studies was confirmed by enzymatic and functional criteria. Orientation of human basolateral membrane vesicles was determined by [3H]ouabain binding studies and was found to be 64% inside-out vesicles and the rest right-side-out vesicles and membrane sheets. Osmolarity studies indicated that the uptake of biotin by these vesicles represents transport into the intravesicular compartment, with little binding to membrane surfaces. The rate of biotin transport was linear for approximately 40 s but decreased thereafter. Transport of biotin was (a) Na+-independent, (b) saturable as a function of concentration, with an apparent KM of 1.1 microM and Vmax of 0.9 pmol/mg protein.15 s, (c) inhibited by structural analogues (desthiobiotin and biotin methyl ester) and related compounds (thioctic acid and thioctic amide), and (d) stimulated by inducing a positive intravesicular electrical potential. These studies are the first to demonstrate the existence of a carrier-mediated transport system for biotin in the basolateral membrane of human intestine. PMID- 3350287 TI - Relationship between distention and absorption in rat intestine. II. Effects of volume and flow rate on transport. AB - Studies in intact animals have shown that intestinal solute absorption may be enhanced with increasing intraluminal volume and flow rate, perhaps because of increases in functional absorptive surface area or perturbation of unstirred layers. We used single-pass perfusions of rat ileum, performed by simultaneously infusing and withdrawing at equal rates, to determine the separate effects of volume and flow rate on solute absorption at pressures between 3.0 and 12.5 cmH2O. Distention enhanced the absorption of passive probes (3H2O, urea), had no effect on the absorption of solutes transported by carrier mechanisms (D-glucose, L-alanine), and led to decreases in the net absorption of sodium and water whenever intraluminal pressure exceeded 10 cmH2O. Increasing flow rate enhanced the absorption of both glucose and 3H2O. However, the effects of increasing flow rate and distention on 3H2O were not additive. In the presence of higher filling volume, faster flow rate led to no further increases in 3H2O absorption; vice versa, at faster flow rate, no further increases in 3H2O absorption were noted when luminal volume was increased. We conclude that increased intraluminal volume enhances the absorption of solutes transported by passive but not carrier mediated mechanisms, perhaps via augmentation of functional absorptive surface area. Increased flow rate and volume may increase the absorption of passively absorbed probes, in part, by a similar mechanism. PMID- 3350288 TI - Reflection and transmission of laser light from the esophagus: the influence of incident angle. AB - The application of lasers in gastrointestinal endoscopy is rapidly expanding. Because of the tubular configuration of the gastrointestinal tract, endoscopists often deliver laser energy at large angles of incidence. As incident angle affects the fraction of radiation reflected from the tissue surface, we measured the transmittance and reflectance of laser light from in vitro esophagus as a function of incident angle, using integrating sphere and goniometric techniques. At a wavelength of 633 nm and angles of incidence less than 50 degrees, the total transmittance of the esophagus is approximately 25% and the total reflectance is approximately 45%; both are isotropically distributed. At larger angles of incidence, a specularly reflected component becomes evident and the total reflectance increases. The absorbed light per unit area illuminated decreases with increasing angle, because the area illuminated by the laser beam is proportional to the secant of the incident angle. The data suggest that during endoscopic laser procedures the incident laser beam should be directed within 50 degrees of normal for optimal performance and safety. PMID- 3350289 TI - Increased hepatic androgen receptor expression in female rats during diethylnitrosamine liver carcinogenesis. A possible correlation with liver tumor development. AB - This study investigated the relationship between liver tumor development and androgen-receptor expression in diethylnitrosamine hepatocarcinogenesis in Wistar rats (SUAH substrain). Random liver samples were assayed by an isoelectric focusing method, with [3H]mibolerone as androgenic radioligand. After 16 wk of oral diethylnitrosamine treatment there was a greater than 20-fold increase in hepatic androgen receptor concentration in female rats (control group 0.3 +/- 0.07 fmol/mg cytosol protein; test group 8.36 +/- 0.96 fmol/mg cytosol protein; p less than 0.001, unpaired Student's t-test). This coincided with, and may be related to, an accelerated development of neoplastic nodules or hepatocellular carcinoma, or both. Male rats showed slower tumor development and no change in androgen receptor concentrations. This model is the first to demonstrate significantly increased androgen sensitivity in experimental hepatic carcinogenesis analogous to increased androgen receptor expression in human hepatocellular carcinoma. It may provide insight into steroid hormone sensitivity in developing tumors, and a means of testing potential therapeutic use of hormonal manipulation in human liver cancer. PMID- 3350290 TI - Ileal excretion of bile acids: comparison with biliary bile composition and effect of ursodeoxycholic acid treatment. AB - The amount of bile acid excreted via an ileostomy at the end of the ileum should give an estimate of the amount of bile acid transported to the colon. In the present study, 8 patients with ileostomies at the end of the ileum but without disease or resection of the small intestine excreted 1690 +/- 205 mumol/day (mean +/- SEM) of bile acids from the ileostomies. In comparison with duodenal bile, cholic acid was increased at the end of the ileum and chenodeoxycholic acid decreased; in addition, bile acid sulfates were increased and bile acid glucuronides were decreased. When ursodeoxycholic acid, a bile acid that decreases biliary cholesterol saturation and dissolves gallstones, was administered at a dose of 500 mg to each subject, 59% +/- 8% (mean +/- SEM) of this bile acid was excreted within 24 h from the ileostomies. It is apparent from these studies that absorption of ursodeoxycholic acid from the small intestine is slower than previously anticipated and involves the entire small intestine and probably also the colon. PMID- 3350291 TI - Quantitative infrared spectroscopy of common bile duct gallstones. AB - The aim of this study was to determine the composition of gallstones from the common bile duct of patients from the United States and the relationship of stone type to the time interval after cholecystectomy. We analyzed 56 sets of common bile duct gallstones collected over a 10-yr period using infrared and atomic absorption spectroscopy and chemical methods. Twenty-four sets (43%) of stones were cholesterol stones containing 85.3% cholesterol, 3.2% pigment, 0.6% phosphate, and 1.3% total calcium. Ten sets (18%) were black pigment stones containing 36.5% pigment, 11.4% cholesterol, 7.6% carbonate, 3.0% phosphate, and 6.2% total calcium. Twenty-two sets (39%) were brown pigment stones containing 52.7% pigment, 16.5% calcium palmitate, 10.1% cholesterol, 0.4% phosphate, and 3.4% total calcium. Most of the 26 stones found at the same time as or within several months after cholecystectomy were either cholesterol (69%) or black pigment (19%). In contrast, the majority (59%) of the 22 common duct stones that were diagnosed greater than or equal to 21 mo after cholecystectomy were brown pigment stones. In conclusion, brown pigment stones are a distinct type of pigment stone characterized by their content of substantial amounts of calcium palmitate. They comprise a significant proportion of common duct stones in this series of United States patients, particularly of those found greater than or equal to 21 mo after cholecystectomy. PMID- 3350292 TI - Chronic pancreatitis and pseudocyst formation secondary to carcinoid tumor of the pancreas. AB - The incidence of chronic pancreatitis has been increasing in the western world. Although chronic alcohol abuse accounts for 90% of adult cases, the physician must be aware of the multiplicity of causes for chronic pancreatitis. We present a case of obstruction of the pancreatic duct and chronic pancreatitis caused by a primary carcinoid tumor. PMID- 3350294 TI - Megaesophagus in mouse--histochemical studies. PMID- 3350293 TI - Charcoal hemoperfusion. Plus ca change, plus c'est la meme chose. PMID- 3350295 TI - Diagnosis of pancreatic infection. PMID- 3350297 TI - Digestive Disease Week and the 89th annual meeting of the American Gastroenterological Association. May 14-20, 1988, New Orleans, Louisiana. Program and abstracts. PMID- 3350296 TI - Secretin test and achlorhydria. PMID- 3350298 TI - Preliminary experience with endoscopic stent placement in benign pancreatic diseases. AB - We treated 35 patients with endoscopic stent placement across the major or minor papilla in an attempt to relieve suspected partial obstruction to pancreatic duct drainage in patients with pancreatitis. The patients subsequently have been followed for periods ranging from 6 months to 3 years (mean, 14 months). Endoscopic stents were successfully placed across the minor papilla in 19 of 22 patients with pancreas divisum associated with acute recurrent pancreatitis (19) and severe abdominal pain (3). 17 patients had symptomatic improvement manifested by a decrease in frequency of attacks of pain and emergency admission. Stents were placed through the major papilla in 14 of 15 patients with recurrent pancreatitis related to a variety of causes. 8 of the 14 patients improved during the follow-up period, including 4 of 5 patients with alcoholic pancreatitis complicated by a segmental stricture. PMID- 3350299 TI - Treatment of acute nontoxic megacolon during colonoscopy: tube placement versus simple decompression. AB - The study compares the efficacy of colonoscopic decompression versus decompression and tube placement in the treatment of Ogilvie's syndrome. Nine patients were treated with a single colonoscopic decompression which resulted in four recurrences. In contrast, there were no recurrences observed in 11 patients who underwent decompression and subsequent tube placement (p less than 0.05). There was no morbidity observed from either decompression or tube placement. Tube placement added less than 10 min of additional procedure time to the colonoscopy. The tube utilized in this study was an enteroclysis tube with sideholes cut in the distal 20 cm. The tube was easily inserted over a Teflon-coated flexible guide wire inserted through the colonoscope into the cecum following decompression. This study demonstrates that colonoscopic decompression followed by tube placement is the preferred treatment modality for acute nontoxic megacolon. PMID- 3350300 TI - Effect of instrument diameter on the depth of penetration of fiberoptic sigmoidoscopes. AB - Newer fiberoptic sigmoidoscopes tend to have smaller diameter insertion shafts than older models. The extent to which this diameter affects how deeply an instrument can be inserted into the colon and the frequency with which sigmoidoscopes of different diameters could reach more proximal areas of the colon was evaluated. Instrument diameter did not influence the length of the sigmoidoscope shaft that could be introduced into the patient. However, when fully inserted to 60 cm, the 12-mm diameter sigmoidoscopes viewed significantly less of the sigmoid and descending colon than did the 16-mm diameter sigmoidoscopes. This lesser degree of anatomic depth of penetration has direct implications for the diagnostic capabilities of smaller diameter instruments. PMID- 3350301 TI - Endoscopic bipolar forceps: a potential treatment for the diminutive polyp. PMID- 3350302 TI - A combined endoscopic and radiological method for biliary drainage. PMID- 3350303 TI - Percutaneous-endoscopic biliary stent placement for Billroth II and total gastrectomy with Roux-en-Y enteroenterostomy. PMID- 3350304 TI - Microcystic adenoma of the pancreas demonstrated by endoscopic retrograde pancreatography. PMID- 3350305 TI - Spontaneous cholecystocolonic fistula treated by endoscopic sphincterotomy. PMID- 3350306 TI - Endoscopic management of retrograde jejunogastric intussusception. PMID- 3350307 TI - Stenting the pancreatic duct--for better or for worse? PMID- 3350308 TI - A frightening event during endoscopic papillotomy. PMID- 3350309 TI - Upper gastrointestinal endoscopy in Turkey: a review of 5,000 cases. PMID- 3350310 TI - Transillumination of light in the right lower quadrant during total colonoscopy. PMID- 3350311 TI - Cecal perforation following flexible sigmoidoscopy. PMID- 3350312 TI - What is the solution to proximal migration of the Amsterdam type biliary endoprosthesis? PMID- 3350313 TI - Intracholedochal knotting of ERCP cannula. PMID- 3350314 TI - Incidence of bacteremia following endoscopic laser treatment of stenosing colorectal lesions. PMID- 3350315 TI - Suggestions for PEG kit improvements. PMID- 3350317 TI - Colonic juvenile polyp and an adenoma in an adult. PMID- 3350316 TI - Spontaneous perforation of the esophagus during gastroscopy. PMID- 3350318 TI - Comparing the diagnostic accuracy of live and recorded electronic video endoscopy and fiberoptic endoscopy. PMID- 3350319 TI - Endoscopic pancreatic drainage in chronic pancreatitis. AB - A nasopancreatic drain, pancreatic duct endoprostheses, and pancreatic stone extraction were used to treat 32 patients with chronic pancreatitis. Thirty patients were treated endoscopically. Endoscopic treatment via the minor papilla in 2 patients with pancreas divisum was not performed. Three patients had subsequent surgery because of complications; one of them died. Seventeen patients with chronic relapsing pancreatitis improved, with 15 patients asymptomatic during a follow-up of 2 to 69 months (median, 11). Seven of 10 patients with chronic pain improved, with 6 patients pain-free during a follow-up of 10 to 34 months (median, 11). In 7 patients, pancreatic pseudocysts could be drained endoscopically by positioning an endoprosthesis into the cyst or by performing a cystoduodenostomy. Six patients had concomitant placement of a biliary endoprosthesis to treat common bile duct strictures within the pancreatic head. One of 32 treated patients died as a result of a complication. We consider endoscopic therapy a viable alternative to surgery in select patients with chronic pancreatitis. PMID- 3350320 TI - [Maternal morbidity following cesarean section: effect of infection control and preventive use of antibiotics]. AB - 1. Between 1976 and 1986, data were collected prospectively by a nurse specializing in hygiene on postoperative infections in the 3508 low cervical cesarean sections carried out at the University Gynecological Clinic in Tubingen. Over the past four years, this has also included data on noninfectious complications. During this 11-year period, the rate of sections rose from 10.3% to 18.2%. 2. During the first seven years, in which only hygienic, organizational, and surgical measures were used to prevent infection, the rate of patients with postoperative infections decreased from 28.2% to 11.9% (-58%), while the rate of feverish standard morbidity decreased from 27.2% to 9.7% ( 64%). 3. Over the past four years, in which 60% of the patients received a perioperative antibiotics prophylaxis consisting of three doses of a cephalosporin, the number of patients with infections has decreased further to 8.6% (-28%), and the number of those with feverish morbidity to 3.7% (-62%). Over the total period, the reduction in the named parameters was 70% and 86%. 4. The most frequent infections were urinary tract infections (mainly cases of asymptomatic bacteriuria), infections of the abdominal wound, and endomyometritis and phlebitis of the arm owing to intravenous applications. Only the reductions in the number of cases of bacteriuria (-77%), wound infections (-72%), and endomyometritis (-73%) reached statistic significance. 5. As a result of antibiotics prophylaxis, the rate of infections in the case of primary section decreased from 15.3% to 9.0%, and in the case of secondary section from 15.1% to 8.2%; feverish standard morbidity decreased from 9.1% to 3.5% and from 9.4% to 4.9%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350321 TI - [Fetal outcome following cesarean section in premature labor. Isthmocorpus longitudinal section or isthmian transverse section?]. AB - Little is known about the comparative safety of the isthmocorporal versus the low transverse uterine incision for Caesarean delivery of the very low birthweight infant. To address this question, the fetal outcome of 59 deliveries by isthmocorporal incision and 76 by low transverse incision were analysed. The incidences of a 5-min-Apgar score of 6 or lower and UA-pH were not significantly different. No correlation was evident between early intraventricular hemorrhage and type of incision. The number of neonatal deaths weighing less than 1000 g associated with vertical incision (27%) was lower than that associated with the low transverse incision (47%). Nevertheless the difference was not statistically significant. The decision for the type of incision should be made intraoperatively by an experienced surgeon. This factor is probably more important than the choice of a particular incision. PMID- 3350322 TI - [Late morbidity following cesarean section--a neglected factor]. AB - Based on the data of a questionnaire this study was designed to follow the obstetrical and gynecological history of 269 women who were delivered at our hospital by Caesarean section during 1960-1969. The Caesarean section group was compared with a control group of 229 women who were delivered spontaneously during the same period. Patients with cesarean sections had less children and more often they had been afraid of further deliveries. In patients with vaginal deliveries there was a significant higher incidence of descensus and prolapse uteri and more often a therapy because of premalignant or malignant diseases of the cervix had to be performed. However, there was no significant difference in the frequency of hysterectomies in both groups. The main indication for hysterectomy in the vaginal delivery group was prolapse and descensus, and in the Caesarean section group fibromyoma of the uterus. Except one case of uterine rupture the rate of complications in subsequent pregnancies was similar for both groups. Compared to the control group a higher rate of maternal morbidity due to Caesarean section could not be proved. PMID- 3350323 TI - [Surgical technic of cesarean section. A preparatory cesarean section method primarily for saving the amnion]. AB - A new technique of Caesarean delivery which makes adequate room for safe and gentle extraction of the infant and prevents injury to the foetus and the uterus is presented. The method consists of careful, layer by layer dissection in the lower uterine segment while keeping - whenever possible - the amniotic membranes intact. The opening can be made as large as needed. In a second step, the amniotic sac, now in full view, is carefully opened and the foetus safely extracted. In the ideal case, the lower part of the still intact amniotic sac containing the presenting part of the infant can be lifted out in front of the incision. There the membranes are opened and the foetus delivered. Bleeding is minimal and injury to the foetus and uterus is almost impossible. The wound can be closed with a single-layer suture, which promotes rapid healing and eliminates the danger of rupture during subsequent pregnancies. Further investigations will be necessary to prove whether this technique - lower cervical transverse Caesarean section with late amniotomy - will be worthy of becoming a standard procedure. PMID- 3350324 TI - [Amniocentesis following premature rupture of fetal membranes and suspected premature rupture of fetal membranes in late pregnancy]. AB - Amniocentesis during the third pregnancy trimenon in case of suspected premature rupture is performed for two reasons: on the one hand, the maturity parameters can be determined as usual from the amniotic fluid, and on the other hand it serves to determine the presence of germs that may have caused the premature rupture. At the same time, it is possible to confirm the suspicion of premature hydrorrhoea gravidarum by instillation of dyestuff into the amniotic cavity. Premature rupture was confirmed in 21 of 65 cases where clinical findings had not supplied safe evidence; in the remaining 44 cases this method permitted the exclusion of premature hydrorrhoea. An evaluation was performed by means of a retrospective study of parturitions between 1975 and 1985 with regard to late amniocenteses in cases of suspected premature rupture, the investigated parameters being the course of pregnancy and of birth, postpartal state of well being, bacteriological findings in the amniotic fluid, and results of instillation of blue dyestuff. PMID- 3350325 TI - [Regulation of the fetoplacental unit. 1. Comparison of the suppressive effect of cortisol and cortisone on estradiol synthesis]. AB - The present study compares the negative feed back action of cortisol and cortison on oestriol production in late human pregnancy. 10 women from the 38th to 40th week of gestation volunteered in this study. All had uncomplicated courses of pregnancy and delivered healthy babies at term. 5 patients received a continuous infusion of 100 mg Cortisol from 10 a.m. to 12 a.m. To the other 5 patients 100 mg Cortison were infused during the same period. Blood specimens (5 ml) were drawn in 60 and 30 minutes intervals from 8 a.m. to 5 p.m. Plasma levels of unconjugated oestriol were measured by radioimmunoassay. The suppression of oestriol levels was nearly identical in both groups: After Cortisol oestriol concentrations decreased from 17.1 +/- 9.1 ng/ml to 6.0 +/- 1.2 ng/ml (p less than 0.001) and after Cortison from 15.5 +/- 5.8 ng/ml to 5.9 +/- 1.8 ng/ml (p less than 0.001), respectively. According to these results the placental metabolism of maternal cortisol to cortison does not impair the negative feed back action of this hormone on the foetal hypothalamus-hypophysis-system. PMID- 3350327 TI - [Perinatal morbidity of breech children in relation to mode of delivery. A retrospective study]. AB - A retrospective study was made on the perinatal morbidity and mortality of 268 infants born from breech presentation in the years 1984-1986. The fraction of vaginal deliveries changed from 12.8% in 1984 to 41.2% in 1986. Criteria for perinatal morbidity were: frequency of transfers to the pediatric department; Apgar score; and the pH in the umbilical cord arteries (pHU.C.A.). After vaginal delivery from pelvic presentation, the average pHU.C.A. was significantly lower than after cesarean section (p less than 0.05) in infants with a birth weight over 2500 g. Severe acidosis (pHU.C.A. less than 7.1) was equally rare in both groups; mild acidosis (7.1 less than or equal to pHU.C.A. less than or equal to 7.2) was more frequent in the vaginally delivered infants greater than or equal to 2500 g; 18.4% as opposed to 3.4% after cesarean section. It is remarkable, however, that mild acidosis was registered in 13-15% of all deliveries in the years 1984-1986. The different frequencies of transfer to the pediatric department and Apgar scores were not due to the different delivery methods. PMID- 3350326 TI - [Antenatal fetal heart rate with special reference to maternal posture]. AB - Between the 20th and 40th week of pregnancy in 40 normal single-fetus pregnancies, examinations were carried out at regular intervals to determine prospectively the influence of gestation age and maternal posture on fetal heart rate patterns. It could be demonstrated that both fetal maturation as pregnancy progresses and differing maternal postures lead to significant changes in the fetal parameters. Failure to take these influences into consideration can lead to a false assessment of the condition of the fetus. PMID- 3350328 TI - [Cerebral convulsion following peridural anesthesia with bupivacaine in cesarean section]. AB - Maternal convulsions and severe fetal bradycardia resulted from the accidental intravascular injection of 0.5% bupivacaine for epidural anesthesia in preparation for caesarean section. Ventilation with oxygen, application of anticonvulsive drugs, relaxation and intubation was promptly performed followed by immediate caesarean section. The newborn was depressed at birth, recovered quickly and showed no neurologic deficits neither in the immediate postnatal period nor in neurobehaviour tests at the age of three months. PMID- 3350329 TI - [Avoidance of homologous blood transfusions in gynecology and obstetrics]. AB - Public concern about the safety of transfusion was aroused by the discovery that the acquired immuno deficiency syndrome (AIDS) can be transmitted by blood transfusion. Patients who require transfusion are now apprehensive to the point of seeking alternatives or even refusing to receive blood. "Autologous transfusion" of the patients own blood can completely eliminate the risk of disease of transmission. Autologous transfusion can be accomplished in different ways: through intraoperative salvage and retransfusion of the patient's blood during surgery, and through donation by the patient of the required amount of blood before surgery. Intraoperative salvage is, to some degree at least, an alternative to transfusion of homologous blood for many surgical patients. Predepositing of blood is an alternative for patients whose elective surgery is scheduled far enough in advance (about 3 weeks) to permit deposit of the required amount of blood. Greater use of predonation would reduce the risk of hepatitis and other transfusion-associated illnesses. It should be noted that any transfusion in obstetrics and gynecology - autologous or homologous - may need a severe indication. PMID- 3350330 TI - Effect of low-dose aspirin treatment on human platelet aggregation. AB - 1. The effect of aspirin 50 mg/day during 28 days on human platelet aggregation (PAG) induced by ADP and collagen has been studied in 12 healthy volunteers. 2. The results show that aspirin treatment reduces both ADP and collagen-induced PAG (P less than 0.01). 3. Maximal inhibition of PAG appears in the second week of treatment for ADP-induced PAG (41.1%) and in the fourth week for collagen-induced PAG (50.2%). No significant differences exist between the controls taken along the treatment during the 28 days of the study. 4. The data suggest that the low dose of aspirin tested provides adequate PAG inhibition to be used in the prophylaxis of thromboembolism patients, thus avoiding intolerances to higher dosages. PMID- 3350331 TI - In vivo studies on toxic effects of concurrent administration of paracetamol and its N-acetyl-DL-methionine ester (SUR 2647 combination). AB - 1. Single p.o. doses of paracetamol 400 and 800 mg/kg or SUR 2647 combination (free paracetamol + paracetamol-N-acetyl-DL-methionate, paracetamol/methionine ratio 2:1) equivalent to paracetamol 400 and 800 mg/kg were given to Bom:NMRI mice. Vehicle treated (1% w/v aqueous methylcellulose) mice were established as a control group. 2. All treatment groups irrespective of medication caused an initial GSH depletion. However, SUR 2647 combination 400 mg/kg caused a much earlier hepatic GSH recovery than paracetamol 400 mg/kg. SUR 2647 combination 800 mg/kg caused a higher hepatic GSH level than paracetamol 800 mg/kg. 3. There was no significant difference in the plasma ALAT level after SUR 2647 combination 400 or 800 mg/kg and the control group. Paracetamol 400 and 800 mg/kg caused significant plasma ALAT elevations compared to the control group. 4. The addition of N-acetyl-DL-methionine esterified to paracetamol, as in the SUR 2647 combination, enhances the hepatic GSH synthesizing capacity in Bom:NMRI mice after experimental overdosage and offers protection of hepatic cell integrity as assessed by plasma ALAT level compared to paracetamol alone. PMID- 3350332 TI - Differential temperature-dependency of electrophysiological and inotropic actions of nifedipine, verapamil and cinnarizine in K+-depolarized ventricular myocardium. AB - 1. Temperature dependency (in the range 27-37 degrees C) of inotropic and electrophysiological effects of equieffective (EC30 at 37 degrees C) concentrations of nifedipine, verapamil and cinnarizine was assessed in potassium depolarized isoprenaline-reactivated guinea-pig ventricular strips. 2. Lowering temperature greatly enhanced nifedipine inhibition of (a) maximal rate of depolarization (Vmax) of slow action potentials and (b) amplitude of contractions. 3. Electrophysiological and inotropic actions of verapamil was virtually unaffected by temperature changes. 4. Negative inotropic action of cinnarizine was greater at 37 degrees C than at lower temperature. At 37 degrees C, but not at 32 degrees C, cinnarizine reduced Vmax of slow action potentials. PMID- 3350333 TI - Evaluation of tussilagone: a cardiovascular-respiratory stimulant isolated from Chinese herbal medicine. AB - 1. Traditional Chinese herbal medicine has long used Kuandong Hua (Tussilago farfara L.) in the treatment of various respiratory conditions. 2. Recently, it has been found that an extract of this plant (7R,14R)-14-acetoxy-7-[(2'E)-3' methylpent-2'-enoyloxy ]-oplopanone, is a potent cardiovascular and respiratory stimulant. 3. This compound has been named Tussilagone (TUS) and when administered intravenously, has been shown to produce an instant and dose dependent pressor effect in anesthetized dogs (0.02-0.3 mg/kg), cats (0.02-0.5 mg/kg), and rats (0.4-4 mg/kg). 4. This pressor effect is similar to that of dopamine; however, no tachyphylaxis has been observed. 5. In addition to its cardiovascular effects TUS produced a significant stimulation of respiration in experimental animals. 6. The acute intravenous LD50 in mice of this compound was 28.9 mg/kg. PMID- 3350334 TI - Pharmacological action of nicotine in the isolated urinary bladder from rabbit: special reference to the chronic nicotine treatment. AB - 1. A mode of action of nicotine and a change of the responsiveness to nicotine following chronic nicotine treatment in the urinary bladder of rabbit were investigated. 2. Nicotine induced only a contraction in the urinary bladder of rabbit, and the response to nicotine was reduced by hexamethonium, atropine and capsaicin. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and partially due to the release of acetylcholine and tachykinins. 3. Tetrodotoxin did not inhibit the contractile response to nicotine in the rabbit detrusor muscle, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 4. Nicotine-induced contraction was reduced following the chronic nicotine treatment without a change of its pharmacological properties. These findings suggest that chronic nicotine treatment might cause a decrease of the amounts of nicotinic receptors and also receptors for mediators released by nicotine. PMID- 3350335 TI - Contractile effect of succinylpurines on guinea pig uterus. AB - 1. The effects of adenosine analogues on isolated guinea pig uterus were studied in vitro. 2. Low concentrations of adenosine analogues contracted guinea pig uterus. The relative potencies of contractive effect were adenosine greater than AMP greater than ADP greater than ATP greater than 2-chloroadenosine greater than N6-phenylisopropyl-adenosine (PIA) greater than 5'-N-ethylcarboxamidoadenosine (NECA) greater than adenylosuccinate greater than succinyladenosine. 3. Pretreatment of the uterus strips with theophylline blocked the action of adenosine. However, dipyridamole did not impair the adenosine actions. 4. The role of naturally occurring adenosine analogues was discussed. PMID- 3350336 TI - Metabolic changes induced by urethane-anesthesia in rats. AB - 1. Fasting hyperglycemia was observed in urethane-anesthetized rats. No significant changes had been observed in fed animals. The effect is dose dependent, being ineffective doses lesser than 1.4 g/kg of body weight. 2. Urethane originates a rise in glycemia during the first 10 min of anesthesia followed by control values at 30 min, and a latter hyperglycemic phase for more than 60 min that remain at 2 hr. 3. The negative correlationship between plasma glucose, lactate and amino acid levels suggest that gluconeogenesis may be the main responsibility of the observed hyperglycemia during the first phase, but it is possible that during the second phase a decrease in the consumption of glucose may take place as a consequence of the competitive effects of ketone bodies increased during the first 30 min of anesthesia. 4. We postulate that the mechanism of the hyperglycemic response to urethane is a sympathetic response with release of catecholamines both in the liver and in the adrenal gland which enhances gluconeogenesis and lipolysis. PMID- 3350337 TI - Community based care. All change at Chiswick. PMID- 3350338 TI - Patients' club. A spot of recreation. PMID- 3350340 TI - Sexuality: never too late. PMID- 3350339 TI - Improving hospital care. PMID- 3350341 TI - Restraint: holding forth. PMID- 3350342 TI - A glimpse behind the curtain. PMID- 3350343 TI - Education: night school. PMID- 3350344 TI - A new beginning. Interview by Linda Thomas. PMID- 3350345 TI - Provision of care: alternative solution. PMID- 3350346 TI - A question of health. PMID- 3350347 TI - Pap smears for cervical cancer: don't neglect the elderly. PMID- 3350348 TI - Neck pain in the elderly: common causes and management. AB - Neck pain is common in the elderly. An outline of the relevant anatomy and pathological conditions which affect the cervical spine and an approach to diagnosis are presented. Intrinsic causes of pain arise in the vertebral column itself--arthritis, discogenic disorders, trauma, tumors, and infection; in the cervical musculature--myofascial pain syndrome, torticollis, and whiplash; and in the spinal cord from tumors. Differentiation of these causes from extrinsic causes of neck pain will enable the appropriate management protocols to be implemented. Many of these problems can be treated effectively at the primary care level. Guidelines for specialist referral are suggested. PMID- 3350349 TI - Time, dose and fractionation in the radiation therapy of cancer. 22nd annual San Francisco Cancer Symposium. San Francisco, Calif., March 7 and 8, 1987. Proceedings. PMID- 3350350 TI - Accelerated repopulation in head and neck cancer. PMID- 3350352 TI - Accelerated hyperfractionation radiation therapy for gynecologic cancers. PMID- 3350353 TI - Facing triumph and disaster--a symposium summary. PMID- 3350351 TI - The place of irradiation in the management of metastatic neck disease. PMID- 3350354 TI - The University of Florida experience with two fractions per day for head and neck cancer. PMID- 3350355 TI - Twice-daily radiation therapy for head and neck carcinomas. PMID- 3350356 TI - Radiotherapy with three fractions per day for twelve consecutive days for tumors of the thorax, head and neck. PMID- 3350357 TI - [Soil protection as a sanitary helminthological problem]. PMID- 3350358 TI - [Hygienic validation of the decontamination of toxic industrial wastes]. PMID- 3350359 TI - [Hygienic aspects of soil recultivation in the working of ore deposits]. PMID- 3350360 TI - [Health and hygiene problems of the irrigation of agricultural lands in a large industrial region]. PMID- 3350361 TI - [Conditions for the formation of elevated pesticide concentrations in the atmospheric ground layer over agricultural fields]. PMID- 3350362 TI - [Detoxication of heavy metal salts during soil self-purification in an experiment]. PMID- 3350363 TI - [Viability of bacterial species in soil contaminated by liquid pig manure]. PMID- 3350364 TI - [Evaluation of magnesium, calcium and 226Ra uptake from soils into agricultural plants]. PMID- 3350365 TI - [First-order tasks in the field of soil hygiene under the 12th Five-Year Plan]. PMID- 3350366 TI - [Characteristics of the hygienic regulation of nitrates in the human daily food ration and individual food products]. PMID- 3350367 TI - [Status and outlook of standardization in the field of protecting against soil pollution]. PMID- 3350368 TI - [Standardization in the field of controlling and protecting against soil pollution in the activities of land users]. PMID- 3350370 TI - [Methodological approaches to assessing the degree of soil pollution by chemical substances]. PMID- 3350369 TI - [Methodological characteristics of determining the air migration index in setting standards for chemical protection agents in the soil]. PMID- 3350371 TI - [A method of determining dioctyl phthalate in water and model media simulating food products]. PMID- 3350372 TI - [Hygienic evaluation of organic substances in industrial sewage used for agricultural irrigation]. PMID- 3350373 TI - [Health and hygiene aspects of the use of the territories of abandoned Don Basin mines]. PMID- 3350374 TI - [Hygienic establishment of the maximum permissible concentration of potassium chloride in the soil]. PMID- 3350375 TI - [Hygienic standards for the polytriazine content in the soil]. PMID- 3350376 TI - [Means of intensification in the hygiene of pesticide use]. PMID- 3350377 TI - [Suppurative-septic complications in long-term catheterization of the blood vessels]. PMID- 3350379 TI - [1-stage operations in tachyarrhythmias combined with other heart diseases and in multiple arrhythmias]. PMID- 3350378 TI - [Surgical results in infectious endocarditis]. PMID- 3350380 TI - [Endovascular occlusion of patent ductus arteriosus by a transvenous approach--an alternative to a surgical operation]. PMID- 3350381 TI - [Potentials of endocoronary x-ray surgery in restoring total and local left ventricular dysfunction in patients with acute myocardial infarct]. PMID- 3350382 TI - [Diagnosis and surgical treatment of ischemic heart disease combined with vasorenal hypertension]. PMID- 3350383 TI - [Extirpation and resection of the bronchi as one of the methods of the surgical treatment of bronchiectasis]. PMID- 3350384 TI - [Current problems of the surgical treatment of bilateral lung diseases]. PMID- 3350385 TI - [Surgical treatment and rehabilitation of patients with chronic lung suppuration]. PMID- 3350386 TI - [Comparative evaluation of multi- and single-stage operations in esophageal cancer]. PMID- 3350387 TI - [Plastic repair using the stomach by the rollover method in cicatricial stenosis of the midthoracic esophagus]. PMID- 3350388 TI - [The problem of angiogenic sepsis in cardiovascular surgery]. PMID- 3350389 TI - [1-stage radical correction of vascular rings and large defects of the interventricular septum in infants in the 1st year of life]. PMID- 3350390 TI - [Comprehensive approach to treating complicated cystic hypoplasia of the superior lobe of the right lung]. PMID- 3350392 TI - Plasminogen. Function, assay and clinical significance. Proceedings of the international meeting and discussion symposium. Vienna, July 2-4, 1987. PMID- 3350391 TI - [Liposarcoma of the mediastinum]. PMID- 3350393 TI - Characterization of commercially available plasminogen preparations in vitro: purity and reactivity. AB - Three different commercially available plasminogen preparations (Immuno-, Kabi-, and Behring-plasminogens) were examined regarding purity and reactivity to different activators (high molecular weight [HMW] or low molecular weight [LMW] two-chain urokinase type plasminogen activator [tcu-PA], single chain urokinase type plasminogen activator [scu-PA], tissue type plasminogen activator [t-PA], and streptokinase [SK]). The Immuno-preparation was a Lys-plasminogen, commercially available for therapeutical use, whereas the research reagents for KabiVitrum and Behringwerke were Glu-plasminogen. Activity data provided by the manufacturers correlated well with our findings. Also a good correlation of reactivity to activators measured with a chromogenic substrate and on fibrin plates could be observed. The Immuno-plasminogen showed a minimum contamination with plasmin which has to be taken into consideration for the interpretation for its apparently higher activation by plasminogen activators compared to the plasmin-free plasminogens. Further in vitro and in vivo research has to be performed to find out criteria for a practicable scheme of administration of fibrinolytic agents for therapeutical thrombolysis. PMID- 3350394 TI - Intermittent plasminogen-streptokinase treatment of deep vein thrombosis. AB - Thrombolytic therapy has been used for treating patients suffering from a variety of clinical disorders including patients suffering from extensive venous and arterial thrombosis. This paper describes a combined approach to lytic therapy consisting of administration of small doses of streptokinase in combination with the infusion of plasminogen. The rationale for this approach is based on recent observations that additional plasminogen will be absorbed into preformed thrombi, rendering them more susceptible to lysis in the presence of activators. Forty four patients who presented with symptoms and signs of acute or sub-acute deep vein thrombosis (DVT) confirmed by phlebography, were included in this study. Group I: 15 consecutive patients received an infusion of 600,000 units of SK dissolved in 50 ml of physiological saline over a period of half and hour. On the subsequent 4 days, a dose of 300,000 units was given twice daily. Group II: 29 consecutive patients received 60 to 90 mg of pretreated plasminogen dissolved in 50 ml of saline given intravenously over 30 min. and followed by same dosage regimen of SK. Blood samples were taken at varying intervals to assess changes in the haemostatic parameters. These were analysed for levels of alpha 2 antiplasmin, antithrombin III, fibrinogen, plasminogen, fibrinogen and degradation products, fibrinolytic activity and levels of activator complex. Findings observed will be presented. Phlebograms were performed before starting treatment and were repeated at the end of 5 days when the treatment had finished. In Group I--(15 patients)--thrombi remained virtually unchanged in 12 out of 15 patients receiving streptokinase infusion; in 3 (20%) there was partial but extensive lysis. In contrast, in Group II--(29 patients)--in 16 (55%) of 29 patients receiving plasminogen and streptokinase infusion, complete lysis of thrombi was obtained. Seven (24%) showed extensive clearance of venous tree while in remaining 6, thrombi virtually remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350396 TI - Haemostasis and thrombosis. New developments in haemostaseology. 5th Congress of the Society on Thrombosis and Haemostasis (GTH). February 24-26, 1988, Frankfurt a.M. Abstracts. PMID- 3350395 TI - Reduced fibrinolytic potential in patients with arterial occlusive disease (AOD) in comparison with normal subjects. AB - When combining angioplasty and local lysis with urokinase (UK) in treatment of peripheral arterial occlusions we have observed marked differences in the individual patient's response irrespective of the age of the thrombus. The extensive arteriosclerotic changes revealed by angiography in some of these patients suggest a reduced fibrinolytic potential depending on the underlying disease. In the standard in vitro test system we measured the UK-dependent thrombolysis in blood samples from 10 normal controls at UK concentrations of 150, 200, and 300 IU/ml of whole blood. In comparison we determined the whole blood thrombolysis time (WBTT) of 10 patients with AOD using UK concentrations of 150, 200, and 300 IU/ml of whole blood. The mean WBTT values for normal controls obtained at UK concentrations of 150 IU/ml, 200 IU/ml, and 300 IU/ml, respectively, amounted to 9.5, 5.5, and 3.5 minutes, respectively, while in patients mean values of 20.7, 8.1, and 5.5 minutes, respectively, were found. Studies on plasma samples had shown that the lysis time could be shortened in a dose-dependent manner by addition of lys-plasminogen (LYS-PLASMINOGEN Steam Treated) and to some extent also glu-plasminogen. Since lys-plasminogen gave clearly superior results we tried to improve the lytic potential in terms of a shortening of the WBTT by adding different doses of lys-plasminogen (0.14-0.56 CU/ml whole blood) to each patient sample. Although the individual response varied, the addition of lys-plasminogen to the patient samples resulted in a clear dose-dependent improvement of pathologically prolonged lysis times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350398 TI - [Stimulating effect of isolated nerve segments on the regeneration of peripheral nerves]. AB - The present paper concerns observations in two series of experiments in which the effect of isolated nerve segments on nerve regeneration was studied. Bridging of a nerve defect with a tube was used as an experimental model--a model often used in studies on nerve regeneration today. In the first series of experiments performed on rats, 14 mm of the femoral nerve were removed and the gap bridged with the femoral vein. A 2-mm nerve segment was inserted at the center of the vein in one group of the animals. In the second experimental series performed on rabbits, 40-45 mm of the peroneal nerve was resected. Up to three segments were introduced into the lumen of the bridging vein. The experiments demonstrated the promoting effect of nerve segments on nerve regeneration and indicated the probable mode of their action: the nerve segments serve as an additional source of Schwann cells and of neurofibroblasts, contributing substantially to the formation of the guiding structures for the axons. The nerve segments are apparently able to develop a similar nerve structure to that formed by the distal nerve stump. However, this ability also appears to be limited to a distance of 10 mm as is the case with distal nerve stumps. These conclusions do not exclude a possible neurotropic action of the nerve segments. PMID- 3350397 TI - [Perilunar dislocations and dislocation fractures--evaluation of treatment results using the newest data on carpal instability]. AB - Between 1956 and 1984, 196 patients with perilunate fracture dislocations were treated at the Unfallkrankenhaus Wien-Meidling. The authors were able to examine 56 of these patients on average 12.5 years after the accident looking specifically at carpal instability. The results showed three patients with dynamic and 21 patients with static instability of the wrist. After having examined the X-rays of all the patients we formulated the following plan: If the dislocation is adequately reduced by closed manipulation, conservative management is successful. But if there remains a pathological radiolunate, scapholunate, or capitolunate angle, operative treatment is indicated. PMID- 3350399 TI - [Trigger wrist. A case report]. AB - The trigger wrist identified by an extraosseous "snap" is very rare. The clinical symptoms and the successful treatment of a patient with a trigger wrist are described. Histopathologically a tendon sheath fibroma was found. The clinical and the pathological symptoms of this patient were compared with those published in the literature. PMID- 3350400 TI - [Radiologic determination of the length of the distal end of the radius and ulna]. AB - The influence of inaccurate positioning of the hand and forearm upon the relative lengths of the ulna and radius is investigated systematically in anatomical specimens and living persons. Increased or decreased ulnar lengths could be produced by moving up and down, by tilting or by pronation of the forearm. Extension of the elbow also influences the ulnar variance measurement. PMID- 3350401 TI - Carpal tunnel release; postoperative care. AB - By demonstrating slight bowstringing of the flexor tendons, computer tomography can explain any weakness of grip. A strong plea for adequate immobilization (three to six weeks) after carpal tunnel release is made. PMID- 3350402 TI - [Morphometry using computerized tomography of the wrist in idiopathic carpal tunnel syndrome. Comparison of pre- and postoperative findings]. AB - Alteration of carpal morphometry after surgical release of the carpal tunnel was investigated in 22 patients with idiopathic carpal tunnel syndrome, using pre- and postoperative computed tomography. The morphometric evaluation showed an increase in carpal volume which was due to a palmar soft-tissue prolapse in 90% and to an increase of the carpal arch cross sectional area in about 10%. The carpal tunnel release caused a palmar opening of the canal most commonly at the pisiform bone. There was also a variation in form and an increase in volume of Guyon's canal. The results are discussed and related to the postoperative complaints. PMID- 3350403 TI - [Aneurysms. A rare cause of ulnar nerve compression in the palm]. AB - A case of an aneurysmatic dilatation of the ulnar artery with compression of the ulnar nerve in Guyon's canal is described. The etiology, symptomatology, and therapy are illustrated. Acute or chronic trauma in the hypothenar eminence caused pain not only here but also in the ulnar side of the hand with paraesthesia in the ulnar region. It was due to compression of the ulnar nerve in the loge de Guyon by a largely dilated and thrombosed arterial aneurysm. The diagnosis was confirmed by angiogram of the arm and hand. Resection and reconstruction was advised and showed good results. PMID- 3350404 TI - [Lassa fever--first case diagnosed in Israel]. PMID- 3350405 TI - [Typhoid fever after splenectomy]. PMID- 3350406 TI - [Spontaneous rupture of aneurysm of the splenic artery in pregnancy]. PMID- 3350407 TI - [Traveller's diarrhea]. PMID- 3350408 TI - [Viral hemorrhagic fever]. PMID- 3350409 TI - [Restless legs syndrome]. PMID- 3350410 TI - [Edematous symmetrical seronegative synovitis of the hands: a new syndrome]. PMID- 3350411 TI - [Early operation in acute prolapse of thrombosed internal hemorrhoids]. PMID- 3350412 TI - [Hypotensive effect of furosemide and verapamil in the elderly]. PMID- 3350413 TI - [Extracranial-intracranial bypass in a meningioma of the cranial base]. PMID- 3350414 TI - [Delayed postoperative hemorrhage from intracranial aneurysm after shunt for hydrocephalus]. PMID- 3350415 TI - [Outcome of primary nephrotic syndrome with minimal changes]. PMID- 3350416 TI - [Masked depression]. PMID- 3350418 TI - [Internship evaluation by Israeli medical graduates]. PMID- 3350417 TI - [Cortical blindness and microangiopathic hemolytic anemia with pulmonary malignancy]. PMID- 3350419 TI - [Clinical significance of antibodies to Ro (SSA) and La (SSB)]. PMID- 3350420 TI - [Cerebral palsy--evaluation of new concepts]. PMID- 3350422 TI - [Empty-sella syndrome]. PMID- 3350421 TI - [Cyclosporin as treatment for insulin dependent diabetes mellitus]. PMID- 3350423 TI - [Renal phosphate leak, rickets and hypercalciuria--a new hereditary syndrome]. PMID- 3350424 TI - [Measurement of bone density and early diagnosis of bone loss by Compton spectroscopy]. PMID- 3350425 TI - [Superior vena cava obstruction]. PMID- 3350426 TI - [Recurrent meningococcemia in hereditary deficiency of seventh complement component]. PMID- 3350427 TI - [Treatment of large low flow vascular malformations of the head and neck]. PMID- 3350428 TI - [Enterogastric intussusception after vagotomy and gastroenterostomy]. PMID- 3350429 TI - [Botulinum toxin for treatment of extraocular muscle disorders]. PMID- 3350430 TI - [Cervico-mediastinal emphysema due to anterior oropharyngeal penetrating injury]. PMID- 3350431 TI - [Anaplastic carcinoma of thyroid without toxic adenoma]. PMID- 3350432 TI - [A hundred year's quest for objective diagnosis of schizophrenia]. PMID- 3350433 TI - [Problems associated with left-sided cardiac valve replacement in children]. PMID- 3350434 TI - [Frequency of treatment of upper limb injuries and their cost]. PMID- 3350435 TI - Total ankle arthroplasty in rheumatoid arthritis: a long-term follow-up study. AB - Patients with rheumatoid arthritis who had undergone total ankle arthroplasty and had a minimum of 2 yr follow-up were studied. Of the original 21 patients 17 were available for review. Twenty-three ankle replacements with an average follow-up of 5.6 yr were studied. On follow-up 2 ankles were rated excellent, 13 were rated good, 4 were rated fair, and 4 were rated poor. Thus, 83% were satisfactory on follow-up. Radiographic analysis revealed migration and settling of the talar component in 14 of 15 cases. Bone cement radiolucencies were found in 14 of 15 cases. Bone cement radiolucencies were found in 14 of 15 tibial components with tilting in 12 of these components. The postoperative position of the implant did not correlate with the development of radiolucencies or migration of the implant. PMID- 3350436 TI - Calcaneal fractures: three-dimensional treatment. AB - A series of 22 calcaneal fractures operated over 4 yr is presented. Radiographic evaluation of these fractures using axial, lateral, anteroposterior, and oblique medial projection (Broden's view) with varying tube angulation toward the head and computerized axial tomography in two planes, coronal and transverse, were done. This repeatedly demonstrated intra-articular splitting fractures along the axis of the os calcis through the posterior facet, extending to the calcaneocuboid joint. These fractures were surgically reduced as described by McReynolds with sequential medial and lateral approaches. Intraoperative X-rays demonstrate the three-dimensional nature of this injury. Bohler's angle may be reconstituted with apparent reduction of the posterior facet when projected laterally; however, Broden's and axial views show persistent widening and split of the posterior facet. The 22 patients have been followed from 12 to 46 mo. All have heels of normal width and wear standard shoes. The first two cases, done only medially, have less than anatomic reconstruction of the subtalar joint. Functional results have been encouraging. Of six active duty members so treated, three returned to full duty, a second who was medically retired as a result of other injuries had minimal heel problems, and fifth had a contralateral open pilon fracture which hampers him, and the sixth patient is now 4 mo postbilateral calcaneal fractures with return to duty anticipated. Most of the 22 have some decrease in subtalar motion without apparent gait abnormality. No cases of medial or lateral impingement or tendinitis are present. Fractures of the calcaneus are amendable to open reduction and internal fixation. Sequential medial and anterolateral exposure allow anatomic reconstruction in three dimensions, avoiding pitfalls of two-dimensional analysis and treatment. PMID- 3350437 TI - Foot breadth in children--its relationship to limb dominance and age. AB - A total of 996 school pupils between the ages of 5 and 12 yr were studied for the relationship between foot breadth and limb dominance. The test of significance and chi-square analysis were used in the calculation. Limb dominance is divided into upper limb dominance (handedness) and lower limb dominance (footedness). No asymmetry or difference was found between the right and left foot (P less than 0.69) in terms of foot breadth. A significant correlation between limb dominance and foot breadth was not found (P less than 0.01). An ipsilateral relationship exists between the two forms of limb dominance-92.37% of right handers are right footed while 51.85% of left handers are left footed. As an offshoot of this work an equation for the estimation of a child's age from his foot breadth is given. PMID- 3350438 TI - Complicated fractures of the neck of the talus. AB - Seven patients with a complicated fracture of the neck of the talus were followed up by a clinical and radiographic investigation. One had an excellent result and four had good results. Four developed avascular necrosis of the body of the talus and the treatment of this serious complication is discussed. PMID- 3350439 TI - Limb salvage in infected lower extremity gangrene. AB - Four diabetic patients with gangrene of the forefoot and infection ascending above the ankle were treated with open amputation of the foot combined with open fasciotomy and debridement of the involved proximal muscle compartments. All four patients healed their wounds and returned to their premorbid community ambulation status. The management and indications in these unusual patients are discussed. PMID- 3350440 TI - Keller arthroplasty. PMID- 3350441 TI - The Second Indo-Pacific Congress on Legal Medicine and Forensic Science. August 14-18, 1986, Colombo, Sri Lanka. Part II. PMID- 3350442 TI - Examinations of ABO bloodgroupings of human hair. AB - In order to bring into play the function of human hair ABO bloodgrouping in the field of medicolegal expertise on material evidence and raise its accuracy, the author, through a test on human hair of 500, makes some emphatic researches on the disposal of hairs, on the application of anti-A and anti-B serum, on the selection of red blood cell indicator and on the elution temperature as well. Five hundred samples of human hair have been examined upon the basis of the improved operation method and through the application of anti-A and anti-B serum, the titer of which being 1:128, and therein, fine results have been obtained. PMID- 3350443 TI - Preparation of high-titre anti-P1 sera for blood typing in man. AB - For the last 25 years, antisera for testing P1 in man have been obtained by i.v. injections in goats using hydatid cyst fluid from livers of pigs infected by Echinococcus granulosus. Due to the fact that this antigen has become very rare today, efforts have been made by the authors to substitute it by different antigens and to save antigen by modifying the technique of immunisation as well. By this, very high titres up to 1:4096 could be reached after specification absorption. PMID- 3350444 TI - The detection and estimation of (A) arsenic in opium, and (B) strychnine in opium and heroin, as a means of identification of their respective sources. AB - Samples of opium with arsenic as an adulterant, and both opium and heroin with strychnine as an adulterant are not infrequently encountered in the local drug scene. The paper describes a method for the possible identification of the sources of opium and heroin in the local market on the basis of an accurate quantitation of the adulterant arsenic and strychnine contents of the respective samples. A possible extension of this concept, would be the possibility of a similar identification of sources outside the country with a view to establishing channels of entry from abroad. Arsenic is determined by the Gutzeit method while strychnine is estimated by high performance liquid chromatography (HPLC). PMID- 3350445 TI - Notes on public protection against hazards and nuisances: the Israeli experience. AB - Scientific, detailed regulations for the abatement of noise, odour and air pollutants did not prove very successful; Israel reverted to the Subjective norm of 'disturbing'. Courts proved more adaptive to change than legislators, and made use of those regulations to shift the onus of proof in keeping balance between sanity and development. PMID- 3350446 TI - Mortuary technicians in Western Australia. AB - After a long and protracted history of quasi-professional assistance to forensic and clinical pathologists, mortuary technicians are gaining recognition and an improvement in status in an unusual and unique vocation. PMID- 3350447 TI - A preliminary test of Pearson's formula for estimation of height of Sri Lankans. AB - The validity of Pearson's formula for estimation of height from the length of bones, has not been tested for Sri Lankan populations. Such a validation was attempted on 27 male cadavers using the recumbent heel to vertex height, and the physiological femoral length. The standard Pearson's formula was found to contain an error in the tested population. Based on these findings, a new formula was therefore evolved where S = 27.48 + 3.08F (as opposed to S = 81.306 + 1.88F in the standard formula). The new formula will be tested further on a larger sample, with a view to making further indicated adjustments. PMID- 3350448 TI - Yellow oleander poisoning--a study of 170 cases. AB - Yellow oleander or Thevetia peruviana is a very common plant in the North of Sri Lanka. Ever since the fact that the fruits and kernel are poisonous was published in the Newspapers, many cases of poisoning due to Thevetia occurred. 170 cases of Thevetia poisoning admitted to the Teaching Hospital, Jaffna in the North of Sri Lanka are studied by the authors. The mortality, morbidity, age distribution, presenting symptoms and clinical findings are analysed. The action of the cardiac glycoside in Thevetia is clearly demonstrated in this study. PMID- 3350449 TI - Respiratory failure from severe organophosphate toxicity due to absorption through the skin. AB - Organophosphates are the most common group of chemicals involved in poisoning in Sri Lanka. Usually, poisoning is by ingestion for suicidal purposes, although accidental poisoning is not uncommon. Poisoning due to absorption through intact or damaged skin is rare. A 32-year-old man was admitted to a peripheral hospital following assault with a 100-ml bottle of insecticide called Monocrotophos, an organophosphate. He had a 2-in. long laceration just above his left eyebrow and there was spilling of the liquid contained in the bottle over his head and face. The liquid was wiped off but the head or face was not washed. After about 3 h the patient developed symptoms and signs of early organophosphate poisoning which were treated with atropine and pralidoxime. On the 3rd day, while on therapy, the patient developed severe weakness of limbs and respiratory distress needing intubation and assisted ventilation. The patient was transferred to the neurology intensive care unit of the General Hospital, Colombo, on the eighth day. His serum potassium levels were low and an ECG showed prominent U waves in all leads. The plasma cholinesterase levels were within 37.5-50% of normal even on the 20th day indicating severe exposure. PMID- 3350450 TI - Exploration of acid gastroesophageal reflux by 24-h pH metry in infants at risk of sudden infant death syndrome: a study of 50 cases. AB - This study focused on the frequency of pathological acid gastroesophageal reflux (AGER) on 50 children considered to be at risk for sudden infant death syndrome: that is to say, 30 near misses and 20 subsequent siblings. Four parameters were studied in a 24-h pH metry: (1) The percentage of time spent at pH less than 4. (2) The length of the longest reflux. (3) The number of refluxes greater than 5 min/h. (4) Esophageal clearance. In comparison to a control group of 46 normal children, we noted a rate of 20% of AGER on the near misses and 31% on children whose siblings had died from sudden infant death syndrome. The pH level of these two groups was significantly more often less than 4, compared to the normal children. The role of AGER in sudden infant death syndrome will, therefore, be discussed. PMID- 3350451 TI - Forensic medicine in The Netherlands. AB - In this paper a review is given of the evolution of the Dutch Forensic Medical Association (Forensisch Medisch Genootschap, FMG): post-graduate education and the position of the police surgeon today in the Dutch legal and medical society. In just a couple of years forensic medicine has grown into a respected form of social health with worldwide contacts. PMID- 3350452 TI - Forensic dental training in Australia. AB - To facilitate in the identification of victims of a major disaster a trained dental manpower reserve is required. In the state of New South Wales, Australia, an annual three-day training course has been designed to familiarize dentists from both the public and private sectors with identification techniques. The course is aimed to preserve the flexibility of personnel so that they can be utilized in a variety of roles rather than rigidly structuring the make up of a team. It is envisaged though, that in a mass disaster situation teams would be specialized into dental autopsy, antemortem or comparison roles. PMID- 3350453 TI - Drugs--a growing problem in Sri Lanka. AB - Cannabis, hashish and opium were the drugs generally abused in Sri Lanka. The laws relating to drugs were consolidated in 1935. Heroin is the most widely abused drug today. Tourists are mainly responsible for the introduction of heroin into Sri Lanka. The separatist terrorists of Sri Lanka are engaged in trafficking in drugs to find the money for the purchase of arms and ammunition. PMID- 3350454 TI - Medical negligence in the U.K.--directions for research. AB - While the debate concerning compensation for victims of medical injury continues unabated, it is presented that many conclusions and recommendations are based on inadequate data. There is a need to examine, not only the legal requisites of a claim, but the factual circumstances surrounding claims. The direction of future studies must include an examination of: the relative experience of practitioners; frequency of medical specialties; demographic characteristics of patients; and the nature of the complaints. PMID- 3350455 TI - Distribution of lidocaine and disopyramide in human blood and tissue, a case report of death caused by spinal anesthesia. AB - An 11-year-old girl was anesthetized with hyper-baric solution of lidocaine as spinal anesthesia for an appendectomy in a surgical clinic. Respiratory arrest which occurred soon after the injection, was not discovered for a period of time. Since spontaneous respiration recovered within 2 h of intensive resuscitation, the patient was transferred to a community hospital for intensive care. Ten hours after the spinal anesthesia, she died of cardiac failure. The concentration of lidocaine in the brain was 5-10 times more than that in other tissues. The relationship between the possibility of malpractice of spinal anesthesia and tissue distribution of the drug was discussed. In addition to lidocaine, a toxic amount of disopyramide, an antiarrhythmic drug, was detected in the body. The distribution of disopyramide was also estimated, and the pharmacokinetics of disopyramide in plasma and tissues were studied experimentally in rats. PMID- 3350456 TI - An enzyme-linked immunosorbent assay for plasma-paraquat levels of poisoned patients. AB - To investigate the efficacy of medical treatments, plasma-paraquat levels were measured in patients who had ingested the liquid weedkiller, Gramoxon, containing paraquat. We determined the levels by an enzyme-linked immunosorbent assay (ELISA) using a murine paraquat-specific monoclonal antibody developed by Niewola et al. (Clin. Chim. Acta, 148 (1985) 149-156). Using this ELISA, concentrations of paraquat in the range 1.56-100 ng/ml could be measured. This assay method had good precision and was suitable for measurement of low levels of paraquat. The therapeutic treatments were most effective on the day of admission. The plasma paraquat levels of poisoned patients decreased significantly. However, the levels tended to increase again during the pause period of the haemoperfusion and this increase was serious for fatal cases. It is clear that elimination of poison not only from blood but also from tissues is necessary to lower the mortality rate. PMID- 3350458 TI - Forensic application of blood stains and polymorphism of the sixth component of human complement (C6). AB - Blood samples from 340 unrelated individuals in Fukui prefecture in the central part of Japan were tested in order to determine the gene frequencies of the C6 common alleles. The gene frequencies calculated were as follows: C6 A, 0.478, C6 B, 0.464, C6 B2, 0.052 and rare alleles, 0.006. It was demonstrated that C6 phenotyping from blood stains aged over a period of 1 year, could be performed correctly. The quantity of detectable whole blood after this period amounted to less than 2 microliter. PMID- 3350457 TI - Potentiation of lethality and increase in body temperature by combined use of d methamphetamine and morphine in mice. AB - Lethality and change in body temperature in mice were examined after subcutaneous injection of d-methamphetamine and morphine alone or in combination. The LD50 values for methamphetamine and morphine were calculated to be 95 and 670 mg/kg body wt., respectively. When a non-lethal dose of morphine (300 mg/kg) was administered with various doses of methamphetamine, the LD50 for methamphetamine was reduced to 5 mg/kg, indicating a marked potentiation of toxicity by combined use of both drugs. Injection of 5 mg/kg of methamphetamine produced slight hyperthermia, while 300 mg/kg of morphine decreased the body temperature of mice. However, when both drugs were used concomitantly, a marked increase in body temperature was observed. Hyperthermia was also observed when the dose of morphine was reduced to 50 mg/kg. It is postulated that hyperthermia is probably one of the contributory factors in the potentiated toxicity by combined use of morphine and methamphetamine. PMID- 3350459 TI - [Fear of AIDS: a new disease? Increasing number of AIDS phobics-- beginning of diagnosis and treatment]. PMID- 3350460 TI - [Chronic respiratory diseases: begin early treatment ! Mortality comparable to lung carcinoma--data on epidemiology and risk factors]. PMID- 3350461 TI - [Cell therapy agents--where do the risks lie?]. PMID- 3350463 TI - [Progress in liver surgery]. PMID- 3350462 TI - [AIDS (HIV infections) in gynecology and obstetrics. Status: December 1987)]. PMID- 3350464 TI - [Healing of arterial and venous ulcers with TCDO. Insight into the mechanisms of tissue repair]. PMID- 3350465 TI - [Abortion refused to underage females despite good reasons. The guardianship law criticizes medical and legal practice in emergency indications]. PMID- 3350466 TI - [Personal experiences with naturopathy: natural urologic agents. Prevention of urinary calculi--urinary tract infections--dietary measures (I)]. PMID- 3350467 TI - [Disseminated surface "actinic" porokeratosis. Possible malignant transformation in 2 out of 3 cases seen]. PMID- 3350468 TI - [Eczema of the dorsum of the foot caused by sensitization to leather]. PMID- 3350469 TI - [Visible stages in nail mycosis. A scanning electron microscopy study]. PMID- 3350470 TI - The role of ovarian sympathetic innervation in the control of estrous responsiveness in the rat. AB - This study examined the contribution of the superior ovarian nerve (SON) to estrous responsiveness and ovarian function in cycling rats. Section of the SON was carried out at 1100 on proestrus, and lordotic responsiveness was measured at 1500, 1700, and 2100 on that day and at 0900, 1200, and 1500 on the day of estrus. SON section decreased lordosis intensity significantly at 1500 and 1700 on proestrus and at 0900 on estrus. Pacing of sexual contacts with males was decreased at 2100 in nerve-sectioned (Nervx) animals when compared with sham operated controls (SHAM). Serum progesterone (P) concentrations were significantly lower in Nervx animals than in Sham animals 30 min after surgery, but were not different between groups at 4.5 hr. Serum estradiol (E2) concentrations did not differ between groups at either time. In addition, Nervx and Sham groups did not differ on measures of pregnancy/pseudopregnancy initiation or on measures of ovarian function 10 days after surgery. These data suggest that the integrity of the SON is necessary for the display of full estrous responsiveness in cycling rats, and suggest that the acute decreases in serum P occurring as a consequence of SON section may be responsible for the deficits seen in Nervx animals. PMID- 3350471 TI - Sexual behavior and sexual orientation of the female rat after hormonal treatment during various stages of development. AB - The amount of circulating sex steroids during Postnatal Days 30-90 was varied in normally developed and in androgenized female rats. The influence of these manipulations on sexual behavior and sexual orientation was investigated. Normally developed or neonatally androgenized females were ovariectomized and implanted with estradiol through Postnatal Days 30-90 or sham-implanted. The remaining subjects were left intact during that period. The hormonal condition during Postnatal Days 30-90 significantly affected the behavior of normally developed females, but affected the behavior of neonatally androgenized females only to minor extent. Estrogen implants in normally developed females enhanced masculine sexual responses and induced a female-directed sexual orientation. Feminine sexual responses were unaffected by this treatment. Sham-implanted, normally developed females showed a male-directed sexual orientation and fewer masculine sexual responses than subjects which were left intact during Postnatal Days 30-90. Neonatal androgen treatment in general resulted in elevated levels of masculine Neonatal androgen treatment in general resulted in elevated levels of masculine sexual responses, inhibited feminine sexual behavior, and facilitated a female-directed sexual orientation. PMID- 3350472 TI - Estradiol benzoate can function as an unconditioned stimulus in a conditioned taste aversion paradigm. AB - The extent to which gonadal steroid hormones can serve as unconditioned stimuli in a conditioned taste aversion paradigm was examined in Rockland-Swiss albino mice. With saccharin serving as the conditioned stimulus, subcutaneously injected estradiol benzoate, but not progesterone or testosterone propionate, was found to be a potent unconditioned stimulus in both male and female mice. Dose-response effects were also observed; increasing dosages of estradiol benzoate led to increasingly stronger conditioned aversions in both males and females. The aversion detected in males was more resistant to extinction than that seen in females. Prepubertal gonadectomy reversed the sex-dependent effects of estradiol benzoate in learned aversions in adulthood; castration of males promoted the extinction process, whereas ovariectomy of females retarded extinction. The results may be useful for our understanding of the mechanisms involved in conditioned taste aversion learning as well as a wide array of hormone-dependent behavioral responses. PMID- 3350473 TI - Sexual coloration, plasma concentrations of sex steroid hormones, and responses to courtship in the female keeled earless lizard (Holbrookia propinqua). AB - The reproductive condition, steroid hormone concentrations in the plasma, and behavior of bright and plain female Holbrookia propinqua were examined. Bright females performed significantly more aggressive rejection of courtship than plain females. Bright females were significantly more likely than plain females to have follicles larger than 5.0 mm or oviductal eggs; females with large follicles or oviductal eggs had significantly higher concentrations of progesterone and androgen than those with small follicles and lacking oviductal eggs. Plasma progesterone, androgen, and estradiol levels in the females studied behaviorally were significantly higher for the bright females than for the plain ones. Females undergoing rapid brightening were significantly more likely to be sexually receptive and copulate than were either plain or fully brightened females. The role of sex steroid hormones in coloration and behavior and the adaptive value of chromatic signalling by females are discussed. PMID- 3350474 TI - Some trends in the responses studied and the species employed by behavioral endocrinologists. PMID- 3350475 TI - Steroidal control of sexual behavior in the rough-skinned newt (Taricha granulosa): effects of testosterone, estradiol, and dihydrotestosterone. AB - Adult, sexually mature, male rough-skinned newts (Taricha granulosa) obtained from a wild population were castrated and received Silastic capsules containing testosterone (T), estradiol (E), or 5 alpha-dihydrotestosterone (DHT). The newts received three capsules of T, either one or three capsules of E or DHT, or combined treatments with these two steroids. When tested for sexual responsiveness after 32 and 34 days of steroid treatment, no group differed from the castrated controls (C). After 74 and 75 days of treatment, more T-implanted than C newts were sexually responsive, but the newts treated with E, DHT, or these two steroids in combination did not differ behaviorally from the C group. The diameter of the vas deferens was greater in the T- and DHT-treated males than in the C males, indicating that the implants adequately replaced testicular androgens. Together with other studies on this and other species, these results confirm the participation of testosterone in the regulation of sexual behaviors in male amphibians. Furthermore, these results indicate that in this amphibian, the behavioral effects of T are mediated directly by this steroid, not indirectly by enzymatic conversion to DHT or E. PMID- 3350477 TI - Prolactin modulation of the maternal-like behavior displayed by juvenile rats. AB - Reports of elevated prolactin (Prl) levels in juvenile rats of the same strain and approximate age, together with the established role of Prl in maternal behavior in adult female rats, prompted us to examine the possible involvement of Prl in the expression of maternal-like behavior in juvenile Sprague-Dawley males and females. Experiment 1 showed that at 25 days of age both sexes exhibited a rapid onset of full maternal behavior (FMB), with males (median = 2.0 days) responding significantly more quickly than females (median = 4.0 days). Moreover, blood sampled for Prl revealed that males had significantly higher levels of circulating Prl than females, (21.0 vs 10.4 ng/ml, respectively). In Experiment 2, CB-154 treatment significantly delayed the onset of FMB in males only, causing latencies to increase to 5.0 days vs 2.0 days for Controls. Female latencies were unaffected by CB-154, 7.0 and 7.5 days for CB-154 and Control groups, respectively. A second set of both male and female juveniles was treated with either CB-154 or vehicle. CB-154 reduced Prl levels in both sexes. In the Controls, the sex difference in Prl levels (males greater than females) was again evident. In Experiment 3 juvenile males were treated with either ovine Prl (0.5 mg) + CB-154, CB-154 + Vehicle, or Vehicle + Vehicle and tested for FMB. Males treated with Prl + CB-154 required 3.0 days to exhibit FMB, significantly faster than CB-154 + Vehicle males which responded in 8.0 days. The response of Vehicle + Vehicle males was intermediate, with a latency of 5.0 days. These results provide support for the idea that Prl is involved in the maternal-like responsiveness shown by 25 day old juvenile males, but that in females a maturational factor may have prevented both heightened responsiveness to pups by 25 days of age and sensitivity to the Prl releasing mechanism(s)/Prl feedback involved in the exhibition of maternal behavior. PMID- 3350476 TI - Estrogen regulation of agonistic and proceptive responses in the golden hamster. AB - The role of estrogen in modulation of agonistic (attack-chase) and proceptive (vaginal-marking) responses of the female hamster toward a male was examined in relation to time course of induction and duration of response. In addition, the sex-specific nature of the vaginal-marking response was examined. Cycling females showed a significantly higher frequency of attack-chase when endogenous estrogen levels were minimal in comparison to that at peak estrogen levels during the estrous cycle. Removal of estrogen (ovariectomy) resulted in a significant increase in attack-chase scores compared to high endogenous estrogen. Addition of exogenous estrogen (Silastic capsule) resulted in a significant decrease in attack-chase scores compared to ovariectomized animals. The inverse effect was found for vaginal marking with the lowest frequency of vaginal marking at low endogenous estrogen levels or following ovariectomy. During high endogenous estrogen levels or following treatment with exogenous estrogen vaginal-marking scores were maximal. Maximal induction of vaginal-marking responses and reduction of attack-chase were found between 6 and 48 hr of estrogen treatment. Both behaviors then returned to the prehormonal treatment level. Failure to detect effects beyond 48 hr was not due to repeated testing, as animals lacking hormone, or animals first tested at 96 hr of estrogen exposure, showed no effect of the treatment. Males gonadectomized as adults never showed vaginal marking, whereas males gonadectomized neonatally showed a low level of vaginal marking which was increased significantly following estrogen treatment. Thus both attack-chase and vaginal marking in the presence of a male are modulated by estrogen. Further, since vaginal marking is estrogen sensitive in the neonatally gonadectomized male, expression of vaginal marking is determined by the hormonal environment during the neonatal period. However, peripheral feedback may be important for frequency of occurrence. PMID- 3350478 TI - Brain arginine vasotocin concentrations related to sexual behaviors and hydromineral balance in an amphibian. AB - Arginine vasotocin (AVT), a potent stimulator of sexual behaviors and regulator of hydromineral balance in male rough-skinned newts (Taricha granulosa), was measured in 11 brain areas using microdissection and radioimmunoassay procedures. A 60-min test for sexual behaviors was used to segregate males into two groups: sexually responsive (initiated amplectic clasping behaviors) and sexually unresponsive (exhibited no sexual behaviors). Compared to sexually unresponsive males, sexually responsive males had significantly higher concentrations of immunoreactive (ir) AVT in the dorsal preoptic area, optic tectum, ventral infundibular nucleus, and cerebrospinal fluid. These results provide evidence for a behavioral action of endogenous AVT in T. granulosa. In another study, irAVT was measured in normal males (control newts maintained in water) and males that were dehydrated for 6 hr. Compared to normal males, dehydrated males had significantly lower concentrations of irAVT in the ventral preoptic area, but not in the other 10 areas of the brain. That different brain areas are associated with sexual behaviors and hydromineral balance suggests that there are some neuroanatomical separations between the behavioral and hydromineral aspects of the vasotocinergic system in this amphibian. PMID- 3350479 TI - Prenatal stress and maternal behavior in intact virgin rats: response latencies are decreased in males and increased in females. AB - The repeated findings that levels of various male-typical behaviors (e.g., copulatory behavior and intermale aggression) are reduced in prenatally stressed (P-S) males, coupled with reports of effects on female physiology and behavior, prompted us to examine the maternal behaviors of P-S animals toward young. Sprague-Dawley female rats were timed-mated (+ sperm = Day 1). From Gestation Days 15 to 22 experimental females were subjected to heat and restraint stress. Control females remained undisturbed throughout pregnancy. The offspring, as adults, were assessed for maternal behavior. P-S males exhibited a significantly shorter latency (in days) to show full maternal behavior (FMB) than Control males, median = 5.0 vs 8.0, respectively. P-S females, on the other hand, exhibited a significantly longer latency than Control females to show FMB (7.0 vs 3.0, respectively). as well as longer latencies to retrieve one, two, or three pups, to begin to crouch over pups, and to build nests in response to young. Sex differences were apparent between Control males and Control females (females were more responsive to young). In contrast, P-S males and Control females exhibited similar latencies to show components of FMB (3-5 days), as did P-S females and Control males (7-9 days). These data demonstrate, therefore, that prenatal stress eliminates the sex difference normally observed in pup-induced maternal behavior. Moreover, the data suggest that prenatal stress renders the male's responsiveness to young more "female-like," while conversely rendering the response of the female more "male-like." PMID- 3350481 TI - Cost containment affects access to new technology. PMID- 3350480 TI - Genotype modulates the aggression-promoting quality of progesterone in pregnant mice. AB - During late pregnancy, female mice of the DBA/2J inbred strain are more likely to exhibit aggressive behavior toward a standard stimulus intruder male than C57BL/6J females. This strain difference can not be accounted for by differences in circulating levels of progesterone (P) since pregnant DBA/2J and C57BL/6J females exhibit similar patterns of the steroid throughout pregnancy. Upon receiving subcutaneously implanted Silastic capsules containing P, virgin DBA/2J mice are more likely than virgin C57BL/6J to respond to the steroid by exhibiting aggression. Strain differences in the aggressive behavior exhibited by pregnant mice may be related to genotype-based variation in central neural tissue sensitivity to P. PMID- 3350483 TI - Hospital cash flow slows. PMID- 3350482 TI - Finance dept. reorganized for managed care. PMID- 3350484 TI - Managing to the budget means reorienting daily operations. PMID- 3350485 TI - Record year for closures in 1987. PMID- 3350486 TI - Provider HMOs catching up with the big boys. PMID- 3350487 TI - 'Blue bloods' come to health care marketing. PMID- 3350488 TI - Mall shopping takes a healthy turn. PMID- 3350489 TI - Good training key to marketing success. PMID- 3350490 TI - Managed care: whoever has the data wins the game. PMID- 3350491 TI - Courts allow MDs to charge job discrimination. PMID- 3350492 TI - Wide impact expected from High Court health care cases. PMID- 3350493 TI - The Corporation: national health care survey. PMID- 3350494 TI - More consumers rely on employers for coverage. PMID- 3350495 TI - Proposals regulating resident work hours stall. PMID- 3350496 TI - ED physician shortage looms. PMID- 3350498 TI - MRI joint venturers overcome difficult odds. PMID- 3350497 TI - The health policy debate: money talks. Interview by Michele L. Robinson. PMID- 3350499 TI - It's back-to-school time for HMO managers. PMID- 3350500 TI - How consumers perceive health care quality. PMID- 3350501 TI - Elder abuse: what role do hospitals play? PMID- 3350502 TI - Space: hospitals' next frontier for savings? PMID- 3350503 TI - The best defense: argue output, not jobs. PMID- 3350504 TI - IG report: PROs need more direction. PMID- 3350505 TI - Future's uncertain for equipment loan pools. PMID- 3350506 TI - Price indicators show hospital costs reflect regional economies. PMID- 3350508 TI - Birth-injury law has quick impact. PMID- 3350507 TI - New risk group for environmental pollution. PMID- 3350509 TI - Is Maxicare on shaky ground or on its last legs? PMID- 3350510 TI - Commercial insurers smarting over 1987 group health losses. PMID- 3350511 TI - Can your advertisements pass a lie detector test? PMID- 3350512 TI - FTC: setting high standards in advertising. PMID- 3350513 TI - Ads: defining MD-hospital relationships? PMID- 3350514 TI - Insurance crisis is over--at least for now. PMID- 3350515 TI - New exemption rules may be just the beginning. PMID- 3350516 TI - Outpatient growth spurs explosive situation. PMID- 3350517 TI - Deja-vu in the outpatient setting? PMID- 3350518 TI - ACOG program eases peer review conflicts. PMID- 3350519 TI - Family MDs in demand. PMID- 3350520 TI - NY state urges MD retesting. PMID- 3350521 TI - Levy sees an end to the "quiet depression". Interview by Alden T. Solovy. PMID- 3350523 TI - Tax status, costs give mission new emphasis. PMID- 3350522 TI - Purchasing trends revealed in exec survey. PMID- 3350524 TI - Next time, don't stand up and cheer. PMID- 3350525 TI - The effects of target wavelength on dynamic visual acuity under photopic and scotopic viewing. PMID- 3350526 TI - The role of stimulus-to-rule consistency in learning rapid application of spatial rules. PMID- 3350527 TI - Hand steadiness: effects of sex, menstrual phase, oral contraceptives, practice, and handgun weight. PMID- 3350528 TI - Isoelectric focusing of superoxide dismutase: report of the unique SOD A*2 allele in a US white population. AB - An isoelectric focusing procedure in an ultranarrow pH range (5.0-5.5) polyacrylamide gel is described for the determination of superoxide dismutase (SOD) phenotypes. The occurrence of the rare SOD A*2 allele in the Caucasian population of Utah is also reported at a polymorphic frequency (0.011). The presence of the SOD A 2 unique allele in the Mormons of Utah is compatible with their historical affinity with Scandinavians. PMID- 3350529 TI - Gc subtypes in Finns, Swedes and Swedish Lapps. AB - The group-specific component (Gc) subtypes were determined by isoelectric focusing and immunoblotting. The gene frequencies in the Swedish Lapps were Gc1F = 0.412, Gc1S = 0.367 and Gc2 = 0.221, which was significantly different from the frequencies found in Finns and in the populations of northern and central Sweden (p less than 0.001). The gene frequencies in the Swedish Lapps, although similar to those in Asiatic populations, are probably not reflecting an Asiatic influence, since the accumulated genetic information on the Swedish Lapps suggests that founder effect and genetic drift are to a large extent responsible for the peculiar gene pool of the original Lapp population. PMID- 3350530 TI - Relationship between placental alkaline phosphatase types and obstetric history of mother. AB - Placental alkaline phosphatase types were studied in 435 samples from Punjab (India). A comparison between women with normal and complicated obstetric histories revealed a statistically significant associations between the Pl1 alleles and higher survival rate of the fetus. The Pl2 and Pl3 alleles were found to be associated with higher rates of fetal loss and various complications of pregnancy. PMID- 3350531 TI - Complement C4 phenotypes in dementia of the Alzheimer type. AB - Complement C4 phenotype distribution was studied in 64 patients with dementia of the Alzheimer type. In contrast to reported findings we failed to find a significant association between C4B2 gene frequency and Alzheimer's dementia. PMID- 3350532 TI - C3 allotypes in pregnancy hypertension and eclampsia. AB - C3 allotyping has been performed on 424 Australian women, 203 with normotensive pregnancies, 161 with hypertensive noneclamptic pregnancies and 60 eclamptic women. The frequency of women heterozygous for 'rare' C3 alleles was 1% in the normotensive women and 3.7% in the hypertensive group. Three out of 25 (12%) of the women with proteinuric hypertension in pregnancy carried 'rare' C3 alleles. This suggested the hypothesis that pre-eclampsia/eclampsia is associated with a higher frequency of rare alleles. The sample of 60 eclamptic women collected to test the hypothesis had no rare alleles, refuting the hypothesis. The frequency of the common (C3F, C3S) alleles did not differ significantly between the three groups. We conclude that there is no evidence for any association between susceptibility to eclampsia and allotypes of the C3 complement component. PMID- 3350533 TI - Transferrin C2 and radiation-induced chromosomal damage. AB - Radiation-induced chromosomal damage (after exposure to 1 Gy) in lymphocytes was studied in relation to transferrin C subtype (C1 vs. C2). In 72-hour lymphocyte cultures a significantly increased frequency of cells with radiation induced aberrations was observed in individuals with the transferrin type C2. Thus the results lend some support to the hypothesis that transferrin C2 may act as an enhancer of chromosomal damage. PMID- 3350534 TI - Esterase D polymorphism in Serbia (Yugoslavia). AB - Phenotypes of human red cell esterase D (EsD) were determined in 351 unrelated adults from Serbia (Yugoslavia). The calculated allele frequencies were 0.911 for EsD1 and 0.089 for EsD2. The phenotype distribution was in good agreement with the Hardy-Weinberg equilibrium. PMID- 3350535 TI - Glyoxalase I polymorphism in Catalonia (Spain). AB - Blood samples from two Catalonian populations (North-East of Spain) were analysed for glyoxalase (GLO) I polymorphism. Gene frequencies of GLO1 (0.46 and 0.41) are comparable to those reported for Central-European Caucasoid populations. PMID- 3350536 TI - Study of possible genetic predisposition to endemic goitre among the Fur and Baggara tribes of the Sudan. AB - The overall prevalence rate of endemic goitre among the Fur and Baggara tribes of Western Sudan was found to be 74%. Family studies in 60 nuclear families showed a significantly higher incidence of endemic goitre among the offspring of affected parents than among the offspring of normal parents. This suggests a possible genetic predisposition to endemic goitre. The proportion of phenylthiocarbamide (PTC) non-tasters was found to be 13% among the goitrous subjects compared to 17.5% among the non-goitrous subjects. However, the association with PTC as well as with 6 blood-genetic markers, was not statistically significant. PMID- 3350537 TI - A study of the range of motion of human fingers with application to anthropomorphic designs. PMID- 3350538 TI - An advanced robot system for automated diagnostic tasks through palpation. PMID- 3350539 TI - An intelligent robotic system for rehabilitation of joints and estimation of body segment parameters. PMID- 3350540 TI - An articulated neurosurgical navigation system using MRI and CT images. PMID- 3350541 TI - Microprocessor-based robotic system for control of fluid connections in the cardiac catheterization laboratory. PMID- 3350542 TI - Biomedical robotics and automation. PMID- 3350543 TI - A miniature electrooptical force transducer. PMID- 3350544 TI - A conceptual framework for tactually guided exploration and shape perception. PMID- 3350545 TI - An insulated dipole applicator for intracavitary hyperthermia. PMID- 3350546 TI - Use of the finite-difference time-domain method for calculating EM absorption in man models. PMID- 3350548 TI - Modeling the excitation of fibers under surface electrodes. PMID- 3350547 TI - A miniature hybrid reflection type optical sensor for measurement of hemoglobin content and oxygen saturation of whole blood. PMID- 3350549 TI - Measurement of low-resistance points on the skin by dry roller electrodes. PMID- 3350551 TI - Latency of the pupillary response. PMID- 3350550 TI - Time-compressed video pictures for vision research. PMID- 3350553 TI - An analysis of the phenomenon of deterioration in the critically ill. PMID- 3350552 TI - Encouraging results in the automated recognition of cerebral palsy speech. PMID- 3350554 TI - Nurses' reactions to difficult patients. PMID- 3350555 TI - Approaches to nursing science methods. PMID- 3350556 TI - Devaluation of biological knowledge. PMID- 3350557 TI - Contributions of Rosemary Ellis to knowledge development for nursing. PMID- 3350558 TI - Health beliefs and adherence in chronic illness. PMID- 3350559 TI - Nursing theories: a critical view. PMID- 3350561 TI - Rejected proposal: what next? PMID- 3350560 TI - Congruence between intershift reports and patients' actual conditions. PMID- 3350562 TI - Advice to the new graduate. PMID- 3350563 TI - Preceptorship and mentorship: bridging the gap between nursing education and nursing practice. PMID- 3350565 TI - International opportunities for nurses. PMID- 3350566 TI - 1988 financial aid survey. PMID- 3350564 TI - Test-taking strategies for the RN-NCLEX exam. PMID- 3350567 TI - What nurses should pack for camp. Interview by Eric Goldman. PMID- 3350568 TI - Cocaine use: your choice now--no choice later. PMID- 3350569 TI - Letter to a high school counselor. PMID- 3350570 TI - Breakthrough to nursing: twenty five years of involvement. PMID- 3350571 TI - Men in nursing. PMID- 3350572 TI - From LPN to BSN: one nontraditional student's view. PMID- 3350574 TI - New graduate nurses: the answer is "Yes". PMID- 3350573 TI - How to survive as a nontraditional nursing student. PMID- 3350575 TI - Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. AB - We have investigated the modulating effect of steroids on the in vitro production of tumour necrosis factor (TNF) by lipopolysaccharide (LPS)-stimulated human monocytes. Dexamethasone, at concentrations ranging from 10(-8) to 10(-6) M, and cortisol, at concentrations 10(-7) and 10(-6) M, suppressed the TNF production in a dose-dependent manner. The highest concentrations of dexamethasone or cortisol reduced the TNF production to 21 +/- 2% and 48 +/- 8% of the control value, respectively. The effect of dexamethasone was time dependent, and an incubation time of 48 hr was required to reduce the TNF production to 21% of control. The effect of dexamethasone decreased when the incubation time became shorter, and the mean TNF production ranged from 49% to 72% of control when dexamethasone was added later than 8 hr before LPS addition, at the time of LPS addition, or within 1 hr after LPS addition. The magnitude of the TNF-suppressing effect of dexamethasone varied greatly from donor to donor. Only the glucocorticoids, and not the sex steroids or the mineralocorticoids, significantly reduced the TNF production. PMID- 3350577 TI - Vaccines to protect Hereford cattle against the cattle tick, Boophilus microplus. AB - Vaccines made from gut and gut and synganglion tissue dissected from Boophilus microplus gave 87% and 80% protection, respectively, compared with adjuvant injected controls in cattle against three infestations with 20,000 larval ticks administered over 14 days. A vaccine prepared from synganglion alone did not protect cattle. Ticks collected from vaccinated cattle produced 95% and 91% fewer eggs, respectively, than ticks from control animals. Vaccinated cattle were protected (36%) 7 months after they had been immunized with tick antigens. Antibody responses to the vaccines were detected by enzyme-linked immunosorbent assay (ELISA). PMID- 3350576 TI - Differential MHC class II expression on human peripheral blood monocytes and dendritic cells. AB - Both monocytes (MO) and dendritic cells (DC) in human peripheral blood are of a plastic-adherent nature. The expression of the MHC class II sublocus products HLA DP, -DQ and -DR on human peripheral blood transiently adherent cells (TA) was examined by an immunocytochemical staining technique. While most TA showed strong expression of molecules of the HLA-DR subtype, only a small proportion of cells (2-6%) showed strong HLA-DP or -DQ positivity. This strong expression of the HLA DP and HLA-DQ sublocus products by a subset of TA was seen only after short-term culture; freshly isolated cells expressed comparatively low levels of these molecules. Enrichment for Fc receptor-negative or low-density cells from TA produced populations with strong HLA-DQ and -DP expression. Such co-enrichment of the strongly HLA-DQ+ and strongly HLA-DP+ cells suggests that the same cells express high levels of both types of MHC class II molecule. Immunocytochemical analysis of TA indicated that the strongly HLA-DQ+ cells, at least, were only weakly or non-reactive with the MO-specific monoclonal antibodies OKM1, UCHM1, MO2 and EB11. In addition, strongly HLA-DQ- or -DP-positive cells were poorly phagocytic in comparison with the majority of adherent cells. The apparent FcR negative, low-density and weakly phagocytic nature of the strongly HLA-DQ/DP+ cells, combined with their lack of reactivity with several MO-specific antibodies, suggests that they may represent the DC component of TA. Such strong HLA-DQ/DP expression by DC may aid their positive identification in human peripheral blood and may be of relevance to DC function in antigen presentation. PMID- 3350578 TI - Simultaneous inhibition of multiple steps in the processing of N-linked oligosaccharides does not impair immunoglobulin secretion from rat hybridoma cells. AB - The effects of inhibiting selected pairs of oligosaccharide-processing activities upon the secretion of IgM and IgG molecules have been investigated. In the presence of castanospermine (CSP) plus swainsonine (SW) or deoxynojirimycin (dNM) plus deoxymannojirimycin (dMM), secretion of IgM and IgG from rat hybridoma cells was unimpaired relative to control cultures. The structures of the N-linked oligosaccharides found on the Ig heavy chains isolated from treated cells or culture supernatants were shown to be qualitatively different from those associated with control Ig by persistent sensitivity to digestion by endo H. Furthermore, the electrophoretic mobilities of mu and gamma chains on SDS-PAGE derived from treated cells were consistently slower than those of control heavy chains. IgM and IgG were also efficiently secreted when all glucosidase and mannosidase activities were blocked, and the secreted heavy chains bore endo H sensitive oligosaccharides. The data suggest that Ig secretion from hybridomas can proceed in the absence of N-linked oligosaccharide processing. PMID- 3350580 TI - The identification of factors in seminal plasma responsible for suppression of natural killer cell activity. AB - We have identified two components of human seminal plasma which suppress natural killer (NK) cell activity in vitro. Dialysis and gel filtration experiments have shown both components to be of low molecular weight. The first will suppress NK cells following a short period of pretreatment, but this suppression is dependent upon the presence of bovine serum in the medium and is directly related to a loss of cell viability as measured by trypan blue dye exclusion. We suggest that this molecule is a polyamine. The second factor will not suppress NK activity following pretreatment of lymphocytes, but is a potent suppressor when added for the duration of the assay. This suppression is completely bovine serum independent, unrelated to toxicity and appears to be mediated by prostaglandin E2. The relevance of these results to a clinical situation is discussed. PMID- 3350579 TI - The effect of aging on the secretory immune system of the eye. AB - The objective of the present study was to examine the influence of aging on the ocular secretory immune system of the eye. Levels of IgA and free secretory component (FSC) were measured in lacrimal glands and/or tears of 0.6, 1.3, 3, 8 and 17-month-old male and female rats. In addition, the FSC output of lacrimal tissue cultured in vitro was evaluated. During the period from 0.6 to 1.3 months of age, the content of tear IgA increased nine- and 13-fold in females and males, respectively. This rise was paralleled by changes in the concentration of tear FSC. Prior to the onset of puberty, FSC could be detected in only 7% of tear samples, whereas after pubertal maturation, tear FSC levels had attained adult concentrations. This tear FSC profile was similar to the age-related pattern of FSC output by lacrimal tissue incubated in vitro. Following puberty, tear IgA content continued to increase in both sexes until adulthood (3 months of age) and then plateaued in females from 8 to 17 months of age. In contrast, tear IgA in males appeared to stabilize from 3 to 8 months and then rose significantly to the highest levels at 17 months of age. This increase in males was also reflected in their lacrimal tissue: IgA content underwent a six-fold elevation from 3 to 17 months. Of interest is that the differential kinetics involved in tear IgA and FSC expression resulted in an age-associated decline in the FSC/IgA ratio from post-puberty to senescence. A striking finding in these studies was the persistence of a sexual dimorphism in the secretory immune system of the eye. After pubertal development, IgA and FSC levels were significantly higher in tears of males, compared to those of females, at all ages tested up to 17 months. These gender- and age-related variations in tear IgA and FSC amounts could not be accounted for by changes in either the volume of, or total protein content in, tears. PMID- 3350581 TI - Role of the pineal gland in immunity. III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism. AB - We have recently demonstrated that the pineal neurohormone melatonin exerts important immunoregulatory functions. We now report that exogenous melatonin counteracts completely the effect of acute anxiety-restraint stress on thymus weight and antibody response to sheep red blood cells (SRBC). In addition, administration of melatonin in the evening prevented paralysis and death of mice infected with sublethal doses of encephalomyocarditis virus (EMCV) after acute stress. The anti-stress activity of melatonin was present in mice injected with T dependent antigens, and it was abolished by the contemporary administration of the specific opioid-antagonist naltrexone. This suggests that melatonin exerts its remarkable anti-stress effect on antigen-activated cells via an opiatergic mechanism. These findings have important implications at both basic and clinical levels. They provide a new approach to a possible physiological 'up-regulation' of the immune response under virus- and/or stress-related immunosuppression. PMID- 3350582 TI - Increased production of Kurloff cells and accompanying lymphocyte subset changes in immunized guinea-pigs treated with cyclophosphamide and cyclosporin A. AB - We have used a panel of novel monoclonal antibodies to investigate the influence of cyclophosphamide (Cy) and cyclosporin A (CsA) on blood and spleen mononuclear cell populations in guinea-pigs immunized with ovalbumin (OVA) in complete Freund's adjuvant (CFA). Female animals received, on Day 0, 100 micrograms OVA/CFA in each hind footpad and were treated with either Cy (300 mg/kg i.p., Day -3) or CsA (25 mg/kg orally, daily from Day 0) or with both drugs. Two weeks later, mononuclear cell suspensions were prepared from blood and spleen. Immunocytochemical (alkaline phosphatase anti-alkaline phosphatase) analyses were performed using monoclonal antibodies directed against pan T cells, T suppressor/cytotoxic (Ts/c) cells, a putative T-helper (Th) cell marker, B lymphocytes and to Ia antigen. Cy and CsA, particularly the former, caused depletion of T cells, although no striking differential effect of either drug was observed on the T-suppressor cell population. Cy caused a more severe depletion of B-cell numbers, whilst CsA selectively spared these cells. The number of Ia positive mononuclear cells also decreased markedly in the blood of animals given either drug and in the spleens of those guinea-pigs given both Cy and CsA. In contrast, absolute numbers of Kurloff cells (mononuclear leucocytes unique to the guinea-pig and possessing a proteoglycan-containing inclusion body) were markedly increased in the blood and spleen of animals given Cy and CsA compared with animals given Cy or CsA alone. Phenotypic analysis revealed that the Kurloff cells bore the pan T-cell marker, (but neither the Ts/c nor Th subset markers) and were Ia positive. The model described provides an opportunity for further characterization of these cells, their function and of factors regulating their production. PMID- 3350583 TI - Comparison of human monocytes isolated by elutriation and adherence suggests that heterogeneity may reflect a continuum of maturation/activation states. AB - Monocytes are heterogeneous both in terms of physical properties and in their functional capacity. Isolation of monocytes from peripheral blood may perturb the observed heterogeneity for purified cell preparations. To explore this possibility we examined monocytes prepared by two techniques, counter-flow centrifugation elutriation (CCE) and fibronectin adherence, in terms of cell surface molecule expression and several physical properties. Although such cells would be expected to represent dissimilar cross-sections of the total monocyte population, they were found to have similar cell-surface antigenic profiles. Observed differences in levels of expression of several molecules (CR1, CR3 and the antigen recognized by LP9 antibody) were found to be a temperature-related phenomenon. These results indicate that monocytes are not divisible into 'subpopulations' on the basis of cell-surface molecule expression and suggest that heterogeneity of monocytes may reflect the presence in the circulation of a continuum of maturational/activation states. PMID- 3350585 TI - Isotype restriction of murine antibodies towards the loop region of hen's egg white lysozyme. AB - Monoclonal antibodies specific for the loop determinant (residues 64-80) of hen's egg white lysozyme demonstrated an immunoglobulin class restriction. Only IgM response against the loop could be evoked in mice, irrespective of whether the immunogen was the intact native lysozyme as such, or the loop peptide covalently conjugated to a synthetic carrier, poly-DL-alanyl-poly-L-lysine (A-L). Despite the fact that in polyclonal antisera from mice immunized with lysozyme, the ELISA titre of anti-loop reactivity was very low, 26% of the total anti-lysozyme response could be accounted for by the loop when expressed as the percentage of anti-lysozyme hybridoma colonies producing monoclonal antibodies reactive with the loop. The results can be interpreted either as determinant controlled isotype restriction, or alternatively, as an affinity restriction leading to the phenomenon that antibodies of isotypes other than IgM are formed, but are of too low avidity to be detected by the ELISA method. PMID- 3350586 TI - Cytostatic and tumoricidal activities of tumor necrosis factor-treated neutrophils. AB - When incubated with recombinant human tumor necrosis factor (TNF), polymorphonuclear neutrophils (PMN) were highly cytostatic to all three tumor cell lines tested. The cytostasis was dose-dependent for both PMN and TNF, and could be neutralized by antibodies specific for TNF. It could also be abrogated by catalase but not by superoxide dismutase (SOD), suggesting that the hydrogen peroxide generated by the TNF-activated PMN was involved in the cytostasis. TNF treated PMN were also cytotoxic to the tumor cells. However, high level of tumor cytolysis was not evident until after long (greater than 24 h) incubation. PMID- 3350584 TI - Identification of colony-forming activities of various hemopoietic cells in the serum-free culture medium of a human embryo fibroblast cell strain. AB - Ralph et al. reported that human cell lines for the production of colony stimulating factor cannot secrete the factor in serum-free media (Blood 68, 633 639, 1986). However, we found various colony-forming activities to be present in the serum-free culture medium of a human embryo fibroblast cell strain (YH-1). When a soy bean trypsin inhibitor was added to the serum-free media, semisolid cultures of mouse and human bone marrow cells exhibited a considerable degree of colony formation by macrophages and to a lesser extent by other cells. A difference in apparent molecular weights in macrophage colony-forming activities by YH-1 cells from serum-free and serum-containing cultures was observed. The physiological significance of these findings is discussed in terms of regulation of hemopoietic cell differentiation by human embryo fibroblasts. PMID- 3350587 TI - Monoclonal antibodies against Fel d I and other clinically relevant cat allergens. AB - Several mouse monoclonal antibodies (MAbs) were obtained which specifically recognized allergen molecules from cat dander extract. Two of them (C5.8 and C5.24) were specific for the main cat allergen, Fel d I. One (C5.25) recognized an important allergen with approximate molecular weight of 30000 Da and a pI between 3.9 and 4.3. A third group of MAbs comprised several hybridomas which were specific either for cat albumin or cat immunoglobulin. The immunochemical characterization and the clinical significance of the cat dander components recognized by these MAbs is presented and discussed. PMID- 3350588 TI - Race and sex differences in the correlates of blood pressure change. AB - Potential predictors of systolic and diastolic blood pressure change between 1960 and 1967 in the biracial population of Evans County, Georgia, were investigated. An all possible regressions multiple linear regression analysis was used. For systolic blood pressure change, the level of systolic blood pressure, age, and change in Quetelet index were significant (p less than 0.05) correlates in white men. The level of systolic blood pressure, the level and change of socioeconomic status, change in Quetelet index, and change in cholesterol were significant correlates for white women. The level of Quetelet index was of borderline significance (p less than 0.055) when the other significant variables were included in the model for white women. The change in Quetelet index was the only significant correlate of systolic blood pressure change in blacks. For diastolic blood pressure change, age, change in hematocrit, and change in Quetelet index were significant correlates for white men. Age, level and change of socioeconomic status, level and change of Quetelet index, and change in hematocrit were the significant correlates in white women. In black men, change in Quetelet index and age were significant. In black women, only age was a significant correlate of diastolic blood pressure change. These results indicate that there may be important differences in these correlates between race-sex groups and thus in the mechanism of blood pressure change for different race-sex groups. groups. PMID- 3350589 TI - Single versus triplicate measurements of blood pressure and heart rate. AB - The mean of rapidly repeated duplicate or triplicate measurements is often used in studies of antihypertensive drugs. Forty patients with hypertension had triplicate measurements of blood pressure and heart rate on two occasions, 1 week apart, during placebo treatment. The average difference between the first measurement and the mean of the triplicate measurements was -0.3 mm Hg. The average coefficient of variation for supine and standing, systolic and diastolic blood pressures was 8.4% for the single measurements and 8.0% for the mean of triplicate measurements. The correlations between the first measurements and the mean of triplicate measurements ranged from 0.90 to 0.98 (all p less than 0.01). The average difference between the two visits for all four blood pressure parameters was -0.6 mm Hg for the single measurements and -0.5 mm Hg for the mean of triplicate measurements (all p = NS). These results indicate that 1) blood pressure does not change further after 1 week of placebo treatment, and 2) use of the mean of triplicate measurements of blood pressure and heart rate gives the same result as use of single measurements, and the results are no less variable. PMID- 3350591 TI - Whole-day blood pressure. PMID- 3350590 TI - Development of hypertension after correction of primary hyperparathyroidism. AB - A statistical association between hypertension and hyperparathyroidism has been repeatedly reported, but the underlying pathogenetic mechanism has not been elucidated. A 51-year-old woman was hospitalized because of increasing motor disability caused by multiple bone and muscle aches with generalized weakness. She was found to have marked hypercalcemia and hypophosphatemia, increased parathyroid hormone secretion, but normal renal function and blood pressure level. After the identification and removal of a single parathyroid adenoma, the calcium/phosphate metabolism normalized in a relatively short time during which, however, hypertension developed in the absence of any other endocrine or renal dysfunction. A positive, highly significant relationship was observed between the progressive rise in blood pressure and the gradual increase in serum phosphate concentration occurring after the operation, suggesting that, in the hyperparathyroid phase, an underlying trend to hypertension could have been masked by the phosphate depletion, probably through its effects on cardiac and vascular smooth muscle function. PMID- 3350592 TI - Drug side effects, drug-drug interactions, drug resistance, and patient compliance in the management of hypertension. Bethesda, Maryland, April 28-29, 1986. National Institutes of Health workshop. Proceedings. PMID- 3350593 TI - An algorithm for the management of resistant hypertension. AB - Before hypertension can be considered resistant to a rational triple drug regimen in maximal doses, the physician should rule out poor adherence to the regimen (including diet), adverse drug interactions, pseudotolerance (due to fluid retention), office hypertension, pseudohypertension, and an unrecognized secondary cause (e.g., renovascular disease, primary aldosteronism, and pheochromocytoma). When these have been excluded, hemodynamic measurements are indicated to identify the mechanism(s) at fault so that the therapeutic regimen can be modified appropriately. PMID- 3350594 TI - Antihypertensive drug side effects in the Hypertension Detection and Follow-up Program. AB - The 5485 participants in the Hypertension Detection and Follow-up Program, Stepped-Care group form one of the largest groups to date on which detailed surveillance of long-term antihypertensive therapy and drug side effects has been reported. During a 5-year period, among all hypertensive persons (mild, moderate, and severe combined) who were not taking antihypertensive medications at the beginning of the study and who attended the clinic at least once during the 5 year trial, a total of 9.3% had definite or probable side effects severe enough to cause discontinuation of the drug treatment in question. Less than 1% of active participants required hospitalization for side effects. No death that could be attributed to side effects was detected. Thus, the Hypertension Detection and Follow-up Program data, which have previously demonstrated the beneficial effects of antihypertensive therapy, confirm the relative safety of such therapy. PMID- 3350595 TI - Resistant hypertension. Introduction and definitions. AB - The following definition of resistant hypertension is proposed: Provided that adherence to the regimen can be assured, hypertension should be considered resistant if the blood pressure cannot be reduced to less than 150/100 mm Hg by a rational triple drug regimen, including a diuretic, prescribed in nearly maximal doses and if the pretreatment blood pressure was greater than or equal to 180/115 mm Hg. If the pretreatment blood pressure was less than 180/115 mm Hg, resistance should be defined as failure to achieve normotension (less than 140/90 mm Hg) on a rational triple drug regimen in nearly maximal doses. PMID- 3350597 TI - [The auxiliary nurse in the year 2012: an assured value]. PMID- 3350596 TI - Prevalence of drug resistant hypertension. AB - Hypertension patients (1781), drawn from seven large employee groups in and around New York City, were studied to determine the prevalence of resistant hypertension among them. The blood pressure criteria for resistance (potential resistance) were failure to reach and maintain a blood pressure less than 160/95 mm Hg on two separate occasions during at least 1 year of treatment. Confirmed resistance required that during the same period of follow-up, in which at least two antihypertensive agents had been prescribed simultaneously, blood pressure control had not been achieved. Potential resistance during 1 year of treatment was found in 75 patients (4.2%), and confirmed resistance for the same period was found in 52 patients (2.9%). Diastolic resistance was far more common than systolic; the systolic/diastolic resistance was the rarest of all. Of the 52 patients with confirmed resistance for the first year, 33 achieved control in subsequent years. In sum, true resistance as defined by rigorous criteria pertaining to the hypotensive effects of pharmacological intervention in the general population is exceedingly rare. PMID- 3350598 TI - Circadian rhythms in the urinary excretion of heavy metals and organic substances in metal workers in relation to renal excretory mechanism: profile analysis. AB - Circadian rhythms in the urinary excretion of eleven heavy metals and organic substances were examined under free, water-restrictive and water-loading conditions for 6 d (2 d for each of the three conditions) in twenty metal workers exposed to lead, zinc and copper. Circadian rhythms were found for all heavy metals and organic substances as well as for urinary flow (UF) rate, creatinine (Cn) and total urinary solutes (TUS). The Cn rhythm was significantly unparallel to the UF rhythm under the water-loading condition, indicating that the two rhythms were essentially different from each other. Circadian rhythms of the eleven urinary substances were then related to the Cn and UF rhythms, using profile analysis. The results indicated that the rhythms in the manganese, chromium, copper and beta-2-microglobulin excretion depend on the Cn rhythm, i.e. the rhythm of glomerular filtration; the rhythms in the hippuric acid, delta aminolevulinic acid and TUS excretion are on the UF rhythm, i.e. the rhythm of reabsorption by the distal tubule and collecting duct. On the other hand, the rhythms in the lead, inorganic mercury, cadmium, zinc and coproporphyrin excretion were considered as reflecting complex renal excretory mechanisms. PMID- 3350599 TI - Mutual metabolic suppression between benzene and toluene in man. AB - The exposure intensity during a shift and the metabolite levels in the shift-end urine were examined in male workers exposed to either benzene (65 subjects; the benzene group), toluene (35 subjects; the toluene group), or a mixture of both (55 subjects; the mixture group). In addition, 35 non-exposed male workers (the control group) were similarly examined for urinary metabolites to define background levels. A linear relationship was established between the intensity of solvent exposure and the corresponding urinary metabolite levels (i.e. phenol, catechol and quinol from benzene, and hippuric acid and o-cresol from toluene) in each case when one of the three exposed groups was combined with the control group for calculation. Comparison of regression lines in combination with regression analysis disclosed that urinary levels of phenol and quinol (but not catechol) were lower in the mixture group than in the benzene group when the intensities of exposure to benzene were comparable, indicating that the biotransformation of benzene to phenolic compounds (excluding catechol) in man is suppressed by co-exposure to toluene. Conversely, metabolism of toluene to hippuric acid was suppressed by benzene co-exposure. Conversion of toluene to o cresol was also reduced by benzene, but to a lesser extent. The significance of the present findings on the mutual suppression of metabolism between benzene and toluene is discussed in relation to solvent toxicology and biological monitoring of exposure to the solvents. PMID- 3350600 TI - Carcinomas of the urinary bladder in a 4-chloro-o-toluidine cohort. AB - In an historical mortality study, conducted on a cohort of 335 male employees in 4-chloro-o-toluidine (4-COT) production and processing plants, no deaths due to cancer of the urinary bladder had been identified. However, after completion of this study, urothelial carcinomas were recorded in eight of the employees, two of whom have died in the meantime (as of December 1986). All eight persons had been employed in the 4-COT production plant before improvements in industrial hygiene were introduced in 1970 (a subcohort of 116 men). This presumably higher level of exposure to monocyclic arylamines lasted for 14.0 years (median), and the total exposure time (before and after 1970) in the 4-COT plant was 25.5 years (median). The standardized incidence rate for urothelial carcinomas in the 4-COT subcohort was 73 times higher than expected and was comparable with the results obtained for polycyclic arylamines, which have been identified as human carcinogenic agents. On the basis of our results as association may be postulated between occupational exposure to 4-COT and carcinomas of the urinary bladder observed among production workers. PMID- 3350601 TI - Excretion of N-mononitrosopiperazine in urine in workers manufacturing piperazine. AB - Piperazine has been shown to nitrosate in vivo to N-mononitrosopiperazine (MNPZ) by oral intake. Urine from workers exposed to piperazine in a chemical plant was analysed for nitrosamines by gas chromatography-thermal energy analysis. In five out of 11 exposed cases, MNPZ excretion in urine was 0.3 to 4.7 micrograms/24 h (during and after a work shift). In four cases, MNPZ was detected in some urine samples, and in two cases MNPZ was not detected (less than 0.1 ng/ml). The individual excretion was strongly dependent on piperazine exposure, which ranged from 0.06 to 1.7 mg/m3 (time-weighted average; Spearman's rank correlation 0.78, P = 0.01). The MNPZ excretion showed no significant correlation with nitrite or nitrate in saliva (both: r = 0.50, P = 0.10). PMID- 3350602 TI - Toluene in venous blood during and after work in rotogravure printing. AB - Toluene exposure was studied in 62 male rotogravure printers, employed in three plants. The exposure level as measured by personal sampling during a week ranged from 8 to 1080 mg/m3 (median 96). The concentration of toluene in venous blood sampled directly after work correlated significantly with the time-weighted average (TWA) for toluene in air during the preceding workshift (n = 57, Spearman's r = 0.84, P less than 0.00001). The post-shift toluene level in venous blood is usable for biological monitoring of exposure. An air level of 100 mg/m3 corresponds to an average blood toluene level of 2.9 mumol/l; an air level of 300 mg/m3 to 8.2 mumol/l. The elimination of toluene is slow. Thus, toluene was detected in most Monday pre-shift blood samples and the levels increased statistically significantly during the work week (median 0.21 versus 0.42 mumol/l, P less than 0.0001). The toluene level in venous blood sampled directly before work on Thursday/Friday was found to be a function of the estimated mean exposure during the work week. In a multiple linear regression analysis, the mean exposure during the week was a good predictor for the concentration of toluene in venous blood before work at the end of the week (n = 52, r = 0.71). Thus, pre shift blood values at the end of the week can be used as a biological index for the weekly exposure, when the variation of the ambient toluene concentration is known. The slow decrease of toluene in venous blood was followed in six workers for two weeks after cessation of exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350603 TI - Variables influencing cadmium concentrations in hair of pre-school children living in different areas of the Federal Republic of Germany. AB - The influence of several factors on cadmium (Cd) concentrations in the hair of 474 pre-school children was examined. The study was performed in an industrial (Duisburg) and rural area (Westfalen) of the (FRG). Season, sex, hair color, and place of residence were found to be the main factors influencing Cd levels in hair. Concentrations of Cd in samples obtained during summer were on the average nearly twice as high as those sampled during winter (geometric means: 116.1 vs. 63.7 ng/g). Boys had more Cd in their hair than girls (111.5 vs. 74.0 ng/g). Cd levels in hair decreased from red to blond, to brown, and black hair. Children living in Duisburg had more Cd in their hair than those from rural areas (103.9 vs. 77.0 ng/g). Cd content in hair was inversely related to age. PMID- 3350604 TI - Diazo-positive metabolites in urine from workers exposed to aromatic nitro-amino compounds. AB - The amount of diazo-positive compounds in urine from workers at a chemical plant producing pharmaceuticals and explosives was determined in samples collected after work and after a holiday. Forty-five persons working with aromatic nitro amino compounds (ANA) showed a statistically significant (p less than 0.01) increase in the exposed samples (1.21 +/- 1.40 mmol/mol creatinine) compared to the unexposed samples (0.56 +/- 0.31 mmol/mol creatinine). No increase in the level of diazo-positive metabolites was found in the 25 workers not exposed to ANA compounds. In a follow-up study, 32 trinitrotoluene (TNT) workers were divided into three exposure categories and seemed to show a dose-dependent increase in the level of urinary diazo-positive metabolites. However, there was a considerable interindividual variation. The method seems suitable for the biological assessment of exposure to ANA compounds--at least on a group level. This may be valuable, especially in situations where significant dermal uptake is expected. PMID- 3350605 TI - Investigations on the quantitative determination of nickel and chromium in human lung tissue. Industrial medical, toxicological, and occupational medical expertise aspects. AB - Nickel (Ni) and some of its relatively insoluble compounds as well as chromates may be able to induce cancer in the region of the lungs, as well as in the nose and paranasal sinuses after occupational exposure. Latency periods may amount to 20 years and more. The results of recent investigations have shown that these metals cumulate in the lung tissue after inhalation of relatively insoluble chromium and nickel compounds. The quantitative detection of these heavy metals in samples of pulmonary tissue hence permits the amount of past exposure to be estimated. To establish the normal values, samples of pulmonary tissue from 30 normal subjects were investigated for chromium and nickel content. The samples were taken from different segments and lobes of the lungs, taking topographical anatomical criteria into consideration. In addition, 15 persons who had formerly been exposed to nickel and/or chromium (11 nickel refinery workers, of whom 10 had died of lung cancer, 2 stainless steel welders, 1 foundry worker, 1 electrical technician) were also investigated. From the results of 495 tissue samples from the normal group, median chromium concentrations between 130 and 280 ng/g were calculated, with median nickel concentrations of 20-40 ng/g (wet weight). If these values are related to the nickel concentrations measured in refinery workers, values 112-5,860 times higher were found. The concentrations were about 500 times higher than normal for nickel, and about 60 times higher than normal for chromium in the stainless steel welders. For the foundry workers who died of lung cancer, chromium and nickel concentrations in the normal range were calculated, with the exception of the nickel concentrations in the upper and lower lobes of the right lung. The very high nickel concentrations found in the samples of lung tissue from former nickel refinery workers should be regarded as a guideline with regard to the appraisal of the causal relationship between lung cancer and occupational exposure to relatively insoluble nickel compounds. This result is also supported by epidemiological investigations on this subgroup and must thus be considered etiologically conclusive. For the welders, chromium and nickel concentrations were found that were markedly above normal, but as yet there is no epidemiologically reliable verification for the increased occurrence of malignancies in this occupational group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3350606 TI - Renal function of chrome-plating workers and welders. AB - The influence of occupational exposure to water-soluble chromium (VI) on renal function was examined. In male chrome-plating workers (n = 29), stainless steel welders (n = 45), boilermakers (n = 18) and a control group of workers (n = 71), the level of chromium in the urine (Cr-U), the chromium clearance, and sensitive renal function parameters were determined. The glomerular-function parameters of the chrome-plating workers (Cr-U 1 to 34 micrograms/g creat) and welders (Cr-U 1 to 62 micrograms/g creatine) appeared to differ from those of the boilermakers (Cr-U 0.3 to 1.5 micrograms/g creatine) and controls (Cr-U 0.1 to 2 micrograms/g creatine). The renal function parameters were not related to chromium concentration in the urine or to chromium clearance. PMID- 3350607 TI - Detection of IgE antibodies to a wide range of insect species in subjects with suspected inhalant allergies to insects. AB - Sera obtained from subjects diagnosed on the basis of case history and skin tests as having inhalant allergies to insects, were tested for the presence of IgE antibodies to antigens from the house fly Musca domestica, a blowfly Calliphora stygia, the common clothes moth Tineola bisselliella, warehouse moth Ephestia cautella, cockroach Blattella germanica, carpet beetle Anthrenus verbasci and silverfish Ctenolepisma longicaudata. Approximately one-third of the sera reacted with extracts from all seven species, over half the sera reacted with four of the extracts and only 3 sera proved negative to all of the extracts. Twenty-six of the sera also contained IgE antibodies that reacted with the house dust mite Dermatophagoides farinae. Tests with a further eleven species of flies from the order Diptera and with extracts of the grain borer Rhyzopertha dominica, locust Chortoicetes terminifera and Bogong moth Agrotis infusa revealed strong IgE antibody responses to all of the species. Electroblotting studies revealed up to 15 IgE-binding components in extracts from 11 different insect species including 6 species of flies. Some IgE-binding insect components with similar electrophoretic mobilities indicated the possible presence of common allergens in extracts from different species. In particular, blots of each of the fly extracts showed a dense IgE-binding component of MW approximately 37,000 daltons. 'Pan allergy' to insects may occur in subjects who have been sensitized to one or a few insects and allergenic similarities may extend to at least some other noninsect members of the phylum Arthropoda. PMID- 3350608 TI - The glycoprotein allergen Ag-54 (Cla h II) from Cladosporium herbarum. Structural studies of the carbohydrate moiety. AB - The carbohydrate moiety of an important allergen, Ag-54 in Cladosporium herbarum was studied by alkaline-borohydride treatment, gel filtration, high-performance liquid chromatography, methylation analysis, gas liquid chromatography and mass spectometry. The Ag-54 protein core possessed a very limited number of sugar chains. The carbohydrate moiety consisted mainly of one large highly branched polysaccharide chain which accounted for nearly 75% of the total molecular weight of the glycoprotein. The carbohydrate moiety is made up of D-mannose and D glucose units in pyranose form having D-galactofuranose side chains attached. Mannose is both 1,2- and 1,6-linked, while glucose is 1,4- and 1,6-linked. Some of the 1,6-linked galactofuranose side chains are bound through C-2 of the 1,6 linked mannose units, and the rest to C-3 of 1,6-linked mannose and 1,2-linked mannose units. A few oligoglucosidic chains of approximately 4 glucose units are also attached to the protein. PMID- 3350609 TI - The major allergen of the house dust mite, Dermatophagoides pteronyssinus, is synthesized and secreted into its alimentary canal. AB - The natural production of Der pl, the major faecal allergen from the house dust mite (Dermatophagoides pteronyssinus), was investigated. Mite cultures grown on radiolabelled substrate were examined at intervals over a period of 21 days and incorporation of radiolabel into the mite proteins measured over the time course. Mite proteins were extracted, purified by chromatofocussing and characterized by immunodiffusion, SDS-PAGE, electroblotting and autoradiography. The faecal allergen, Der pl, did not incorporate a significant level of label until the 14th day (p less than 0.05). The results suggest that Der pl is a protein synthesized and excreted by the house dust mite. PMID- 3350611 TI - IgG and IgA subclass distribution of antitoxin antibody responses after oral cholera vaccination or cholera disease. AB - The immunoglobulin subclass distribution of cholera antitoxin antibody responses in serum was studied in Swedish volunteers after different routes of immunization with a cholera B subunit-whole cell vaccine (B + WCV) and in Bangladeshi patients convalescing from cholera disease. Both oral and parenteral immunization induced antitoxin antibodies of all the different IgG subclasses (IgG1, IgG2, IgG3 and IgG4) whilst the IgA antibodies were restricted to the IgA1 subclass. A single oral dose of B + WCV induced proportionally higher levels of IgG4 antitoxin in previously cholera-immunized volunteers than in a matched group who had not been cholera-vaccinated before, suggesting that repeated immunization preferentially stimulate formation of IgG4 antibodies. The IgG and IgA subclass distribution of antitoxin antibodies in orally vaccinated Swedes closely resembled that in Bangladeshi cholera patients. PMID- 3350613 TI - The leader's role in resolving resistances to intimacy in the group setting. PMID- 3350612 TI - Life-skills training with hospitalized psychiatric patients. PMID- 3350610 TI - Comparison of NiSO4 and NiCl2 as sensitizers in the guinea pig. AB - Nickel sulfate (NiSO4) and nickel chloride (NiCl2) were evaluated as sensitizers in the Guinea Pig Maximization Test (GPMT). The highest concentrations of NiSO4 or NiCl2 used as an intradermal challenge (0.25 and 0.5%) yielded responses that were significantly different (p less than 0.05) between exposed and control guinea pigs at 24 h, and the highest concentration (0.5%) yielded significant differences (p less than 0.05) at 48 h. The responses at the 0.125% NiSO4 challenge site were significantly greater (p less than 0.05) than for controls at both 24 and 48 h. Using the lymphocyte transformation test (LTT), the stimulation indices for the NiSO4- and NiCl2- exposed guinea pigs were nearly identical; however, the difference between exposed and control groups was greater for NiSO4 than for NiCl2. The results of both intradermal skin challenge and lymphocyte transformation indicated that NiSO4 may be preferable to NiCl2 in the GPMT. Because the skin test yielded statistically significant results while LTT did not, the skin test may be of more value when using these sensitizers in the GPMT. PMID- 3350614 TI - The experience of shame and the restoration of self-respect in group therapy. PMID- 3350615 TI - Alexithymia: treatment utilizing combined individual and group psychotherapy. PMID- 3350616 TI - Stalking the lost cause: an Aristotelian paradigm for group analysis. PMID- 3350617 TI - DNA patterns and aggressive histopathologic features in 159 patients with cervical carcinoma. AB - In 159 patients with invasive squamous cell carcinoma of the uterine cervix, flow cytometric DNA patterns were related to eight histopathologic parameters according to a malignancy grading system, in which four of the parameters concern the tumor cell population and four concern the tumor-host relation. Each parameter was graded from 1 to 3 points. Flow cytometrically aneuploid values, contrasted to peridiploid ones, were more often found in specimens with immature, irregular nuclei, as well as in specimens with diffuse growth (p less than 0.05), obvious vascular invasion (p less than 0.05) or slight or no plasmolymphocytic response (p less than 0.05). For each histopathologic parameter, higher mean S phase rates were found for the aggressive 3-point tumors than for the 1-point tumors. Tumors with total scores of 11-17 points were more often peridiploid than tumors with 18-22 points. PMID- 3350618 TI - Estrogen receptor distribution in the normal and pathologically changed human cervix uteri: an immunohistochemical study with use of monoclonal anti-ER antibody. AB - Normal and pathologically changed structures of human cervix uteri were examined for estrogen receptor (ER) content using monoclonal antiestrophilin antibody (H 222 SP gamma) and the peroxidase-antiperoxidase method (PAP). The study was performed on fresh-frozen cervical specimens from 30 women; the staining was evaluated semiquantitatively. The ER expression in cervical mucosa was generally strong and comparable to the ER expression by proliferating endometria. The only exception was the endocervical stroma, which showed distinctly weaker specific staining than other cervical structures. This might account for ER concentration gradients observed in biochemical studies. The ER content in endocervical glands varied in different cases and in different areas of the same specimen, but no correlation to the functional activity of the genital tract or to the morphology of the glands could be found. The squamous epithelium of the portio vaginalis contained relatively large amounts of ER in the basal, parabasal, and intermediate layers. The superficial layer was ER-negative. The only factor we observed that strongly influenced the ER content in cervical mucosa was a local inflammatory process. Our results suggest that the synthesis of ER in cervical epithelium can be influenced by underlying stroma. PMID- 3350619 TI - Metaplastic papillary tumor of the fallopian tube: a case report with ultrastructure. AB - This is the fifth metaplastic papillary tumor of the fallopian tube identified in a postpartum tubal ligation. Light microscopic studies demonstrate a mucinous metaplasia. The ultrastructure of this unusual papillary epithelial proliferation reveals abundant filaments with condensations. The tumor has not recurred during 4 years of follow-up. PMID- 3350620 TI - Oncocytic metaplasia in endometrial hyperplasia and carcinoma. PMID- 3350621 TI - Villous adenoma and invasive adenocarcinoma of the cervix. PMID- 3350622 TI - The effect of short-term and long-term femoral artery ligation on rat calf muscle oxygen tension, blood flow, metabolism and function. AB - The effect of short-term (1 day-1 week) and long-term (6-12 weeks) femoral artery ligation on the oxygen tension (pO2), blood flow, metabolism and function of rat gastrocnemius muscle has been examined. Femoral artery ligation reduced resting blood flow, pO2 and pH. Concomitantly, the concentration of high energy phosphates was reduced and the muscle lactate concentration increased. The fatigue developed by the gastrocnemius/plantaris muscle, during a 10 min period of isometric exercise, was increased and the associated hyperaemia was attenuated. The surgery, performed to ligate the artery, induced an increase in the plasma fibrinogen concentration and whole blood viscosity. As the time interval increased after the femoral artery ligation there was a progressive reduction of the magnitude of the effects. Ten weeks after ligation resting muscle concentrations of high energy phosphates and lactate, whole blood viscosity and muscle pH had normalized. However, resting muscle blood flow, pO2, ability to sustained isometric exercise and the exercise induced hyperaemia were still reduced compared to intact animals. Comparison with literature data reveals that the changes produced by chronic femoral artery ligation in rat calf muscle mimic those seen in man with intermittent claudication. PMID- 3350623 TI - An investigation of the routes of venous escape from the diaphyseal marrow of the canine and rabbit long bones. AB - The routes of venous escape from the diaphyseal marrow have been demonstrated by directly perfusing the marrow cavity of canine and rabbit long bones with barium sulphate suspension. Plain radiographs immediately after perfusion revealed prompt escape of dye into the systemic veins via a number of large transcortical emissary veins. A central venous sinus as usually described was not found; instead the dye occupied the whole of the medullary cavity extending from metaphysis to metaphysis. This suggests that the marrow is an open circulatory system with ill-defined boundaries. Radiographs of thin sections of the perfused bone after decalcification, which permitted visualisation of the fine vessel arrangements, revealed numerous haversian venules. These drained the marrow into a separate extraosseous venous network on the surface of the bone. PMID- 3350624 TI - Fine structure of the human skeletal muscle capillary. A morphometric analysis. AB - Capillary dimensions in muscle biopsies from human musculus quadriceps femoris, sectioned at right angle to the muscle fibers, were analysed with a computerized planimetric technique giving distributions of dimensional parameters with statistics. Without corrections for estimated preparative shrinkage mean maximal diameter of lumen was 3.82 +/- 0.82 microns (5.31 +/- 1.14 micron shrinkage corrected), mean second maximal diameter, at right angle to maximal, 2.61 +/- 0.72 microns (3.62 +/- 1.00 microns corr.) and mean endothelial thickness in nuclear free sections 0.35 micron (0.49 micron corr.) micron. Using a capillarity of 360/mm2 for the human m. quadriceps femoris, the total surface area of skeletal muscle capillaries was calculated to be 5.50 X 10(3) cm2/100g and the total volume of the capillary network in the muscle to be 0.48 cm3/100g. PMID- 3350626 TI - AIDS in Iowa. PMID- 3350625 TI - The effect of prolonged total ischemia on the ultrastructure of human skeletal muscle capillaries. A morphometric analysis. AB - Human skeletal muscle shows reflow impairment after prolonged tourniquet ischemia of 1-3 hours, increasing with the duration of ischemia. A sample of 275 cross sectioned capillary profiles from muscle biopsies of human m. quadriceps femoris made totally ischemic by tourniquet for 90-180 minutes (mean 110 min.) from 5 patients during surgery, show frequent evidence of ultrastructural damage to microvascular membranes and organelles. Frequency analyses demonstrate a significant increase in damage during ischemia (p = 0.03), but not increasing further following 5 min of reperfusion. One of the signs of ischemic damage was endothelial swelling, found in some endothelial cells, lying next to ultrastructurally intact ones. The swelling found cannot be explained by a general loss of volume control of the microvascular endothelium during ischemia, since a computerized morphometry on the entire sample shows a preserved capillary wall thickness during ischemia and following reperfusion. During reperfusion the capillaries dilate with an increase in median max. diameter from 3.4 micron (4.7 micron shrinkage-corrected) to 3.9 micron (5.4 corr.) (p less than 0.001), despite reported reperfusion impairment. However, since capillaries in skeletal muscle consist of 20-40 endothelial cells, a distribution of such localized endothelial swelling or luminal membrane changes in a few percent of the microvascular endothelial population after ischemia, trapping leucocytes, would affect microvascular hydraulic conductance to reperfusion. PMID- 3350627 TI - Managing HIV exposure in the hospital setting. PMID- 3350628 TI - Taking sexual histories: now it's essential. PMID- 3350629 TI - Focus on AIDS education. PMID- 3350631 TI - The scourge of the eighties. PMID- 3350630 TI - HIV infection: manifestations, therapy and transmission. PMID- 3350632 TI - Will AIDS cause Semmelweis to triumph at last? PMID- 3350633 TI - Tax free fringe benefits: new restrictions. PMID- 3350634 TI - Iowa Department of Public Health. AIDS Task Force. PMID- 3350635 TI - Colonoscopic polypectomy and management of malignant colorectal polyps--a review in an Irish population. PMID- 3350636 TI - Penicillin-resistant pneumococcus. PMID- 3350637 TI - Trisomy 18: a nine year review. PMID- 3350638 TI - Hyposplenism in inflammatory bowel disease. PMID- 3350639 TI - Birth of a network. The Ethics Committee Network Project. PMID- 3350640 TI - Birth of a network. The Philadelphia story. PMID- 3350641 TI - Where are the ethics in ethics committees? PMID- 3350642 TI - Assessing the risk of legal liability for ethics committees. PMID- 3350643 TI - Networks across America. PMID- 3350644 TI - The inner workings of an ethics committee: latest battle over Jehovah's Witnesses. AB - Jehovah's Witnesses who refuse blood transfusions on religious grounds have long created ethical dilemmas for those in the medical profession trying to serve them. A bioethicist working in a clinical setting explores how one hospital ethics committee grappled with the additional problem of pregnant Jehovah's Witnesses, including the complex interdependence of maternal and fetal rights. PMID- 3350645 TI - Selective termination of pregnancy. PMID- 3350647 TI - The persistent problem of PVS. PMID- 3350646 TI - She's going to die: the case of Angela C. PMID- 3350648 TI - The persistent vegetative state: the medical reality (getting the facts straight). PMID- 3350649 TI - Ethical questions raised by the persistent vegetative patient. PMID- 3350650 TI - From Quinlan to Jobes: the courts and the PVS patient. PMID- 3350651 TI - Not dead, not dying? Ethical categories and persistent vegetative state. PMID- 3350652 TI - Cost constraints as a malpractice defense. AB - Cost-containment pressures impose fiscal responsibilities upon physicians that can conflict with their fiduciary commitment to patients. Should the law permit health care providers to adjust standards of care according to patients' financial resources? The legal concept of "rebuttable presumption" should be used to reconceive the traditional requirement of a uniform standard of care. PMID- 3350653 TI - First episode schizophrenia: three year and sixteen year follow-up. PMID- 3350654 TI - The lost schizophrenics: a retrospective cohort study of discharged patients. PMID- 3350655 TI - Continuing care of the demented elderly in Inverurie. PMID- 3350656 TI - CRAFT: an aid to medical audit, research and patient management. PMID- 3350657 TI - Use of the National Health Service Central Register for medical research purposes. PMID- 3350658 TI - The appropriate use of diagnostic services: (XV). A guide to blood transfusion practice. PMID- 3350659 TI - Skeletal 212Pb retention following 224Ra injection: extrapolation of animal data to adult humans. AB - Two methods of interspecies extrapolation, one based on a correlation of skeletal 212Pb/224Ra with body weight, the other based on the mechanistic relationship between skeletal 212Pb/224Ra and reciprocal bone surface-to-volume ratio, lead to the conclusion that the retention of 212Pb in the adult human skeleton is approximately complete a few days after injection. The correlation-based method gives most probable values for 212Pb/224Ra of 1.0 and 1.1 at 2 d and 7 d after injection, compared with values of 1.05 and 1.27 expected at these same times if the retention of 212Pb were complete from the time of injection and if no 212Pb were in the injection solution. The range of values corresponding to one geometric standard error on either side of the most probable value is 0.87 to 1.21 at 2 d post-injection. With the method based on the reciprocal bone surface to-volume ratio, the best estimate of 212Pb/224Ra at 2 d after injection is 0.88, equal to the value observed in young adult beagles. An alternative interpretation of the results of this latter method leads to the conclusion that retention is complete, with 212Pb/224Ra equal to 1.0 for a 212Pb-free injection solution and 1.1 for a solution containing 212Pb in secular equilibrium with 224Ra. This work, which uses 224Ra daughter product retention data from mice, rats and dogs following 224Ra injection, provides a scientific foundation for retention assumptions made in the calculation of mean skeletal dose for adult humans. There now appear to be few uncertainties in these latter dose values, stemming from inaccurate retention assumptions; but substantial uncertainties remain in the mean skeletal dose values for juveniles and in the endosteal tissue doses regardless of age. Risk coefficients such as those in the BEIR III report that give the lifetime probability of bone tumor induction per unit mean skeletal dose may be correct for adult humans but are probably too low for juveniles due to overestimation of juvenile dose. BEIR III risk coefficients that give tumor induction probability per unit endosteal tissue dose may be substantially too small, regardless of age, due to overestimation of endosteal dose. PMID- 3350660 TI - Doses to patients from diagnostic radiology in France. AB - Reported here are results of a 1982 national survey in France to establish the collective effective dose equivalent associated with the main types of radiological examinations practiced annually in this country (except nuclear medicine, C.T. scans, dental radiology and mass chest screening). This report describes the methodology followed in achieving dose measurements either on an anthropomorphic phantom or directly on the patient, and it highlights the importance of the radiological procedures (number of x-ray films, fluoroscopy screening time, etc.) on the patient organ doses. The estimated collective effective dose equivalent associated with these radiological practices is 86,000 person-Sv, i.e., an individual effective dose equivalent of 1.58 mSv y-1; the genetically significant dose figure is 0.29 mSv and the collective red bone marrow dose due to 45 million x-ray exams practiced in France (1982) is 40,300 person-Sv, i.e. 0.74 mSv per inhabitant. PMID- 3350661 TI - An evaluation of energy-independent heavy ion transport coefficient approximations. AB - Using a one-dimensional transport theory for laboratory heavy ion propagation, evaluations of typical energy-independent transport coefficient approximations are made by comparing theoretical depth-dose predictions to published experimental values for incident 670 MeV/nucleon 20Ne beams in water. Results are presented for cases where the input nuclear absorption cross sections, or input fragmentation parameters, or both, are fixed. PMID- 3350662 TI - Comparative uptake of U and Th by native plants at a U production site. AB - During a 3- to 4-year period, concentrations of 238U, 234U, 230Th, 232Th and 228Th were determined in soils and native vegetation at various sites around a typical U mining and milling operation in Wyoming. Plant/soil concentration ratios (CR) for U and Th isotopes were estimated for (1) exposed, weathered tailings, (2) the edge of a tailings impoundment, (3) an area downwind from exposed tailings, (4) a reclamation area and (5) several background, native range locations. The 238U/234U concentration ratio of 0.9 to 1.1 in soil and vegetation indicated near-radioactive equilibrium of both radionuclides at all locations. Mean concentrations of the U and Th isotopes in background soil ranged from 44 to 52 mBq g-1. Concentrations of 238U and 230Th in soil and vegetation were elevated above background at all sites disturbed by mining and milling activities. Uranium concentrations in tailings and invading vegetation were an order of magnitude greater than in the background locations, whereas 230Th concentrations were elevated above background by some two orders of magnitude. No demonstrable differences in radionuclide concentrations between plant groups and collection years were found. The observed CR values for 238U and 230Th of 0.81 and 0.69 for vegetation growing on exposed tailings were elevated above native range by factors of 9.0 and 3.6, respectively, and generally higher than other published values. Exceptionally high CR values for 230Th (1.9-2.9) observed near the tailings impoundment demonstrate that under certain conditions, vegetation can accumulate 230Th to a much greater extent than previously reported. Vegetation concentrations were lower for 232Th relative to 230Th and 228Th at locations where they are present at similar soil concentrations. PMID- 3350663 TI - Coastal dispersion conditions near the southwestern tip of Africa: a system for evaluation and prediction. AB - A system is presented to monitor the local meteorology and to predict the dispersion of effluents from a nuclear power station situated on the coast near the southwestern tip of Africa. A computerized weather station forms the basis of the system and provides spatial definition of wind profiles and dispersion indices near the coastal interface by interpolation between a sensor array. The meteorological system measures winds, temperature structure and turbulence indices at the 10-m level at five remote points and in the 10- to 80-m layer at the main coastal station. To provide a system for evaluation and prediction of effluent trajectories, a real-time three-dimensional puff dispersion model was developed. The meteorology input to the model is automatically verified and updated at 15-min intervals. Model results are presented under complex weather conditions to show how time and space changes in the local wind field are handled. To assist weather forecasters supporting the nuclear emergency plan, a simple tabular display enables a view of the dispersion climatology over 24-h (coastal) and 7-d (synoptic) cycles. These results are presented to contrast the different scales of circulation and for comparison within the nuclear industry to assist health physicists in deciding appropriate levels of meteorological support for emergency plans. PMID- 3350664 TI - Difficulties encountered with some intermediate-atomic-number radiation protection dosimeters irradiated on-phantom in low-energy photon beams. AB - During a measurement-assurance study done with a particular type of radiation protection dosimeter, we obtained unexpectedly poor results when several of the dosimeters were irradiated simultaneously on-phantom in a low-energy bremsstrahlung beam. The dosimeters incorporated low- and intermediate-atomic number (Z) thermoluminescence dosimeter elements with the intermediate-Z elements under Pb filters. The response of the low-Z elements was in good agreement with the predicted response regardless of dosimeter location on the phantom, while agreement for the intermediate-Z elements was poor for some locations not coinciding with the phantom center. We have since studied the behavior of this dosimeter type and of four other types in detail by irradiating them, one at a time, on- and off-phantom, with their geometric centers displaced up to 10 cm along the vertical and horizontal axes through the center of the beam cross section. Two low-energy bremsstrahlung beams and a 137Cs gamma-ray beam were used. Variation of response to low-energy photons with on-phantom location was observed to some degree in all intermediate-Z dosimeter elements covered with high-Z filters. The reason for the observed dependence of response upon on phantom location seems to be insufficient side shielding against phantom and filter albedo, as proved in one case, in which added shielding removed this dependence for the element immediately adjacent to the added shield. Since the effective dose equivalent to the human body is lower for lateral incidence of low energy photons than for the same photons incident from the front or back, dosimeters incorporating high-Z filters without side shielding (and thus expected to exhibit the phenomenon) do not lend themselves to the determination of the effective dose equivalent or any quantity proportional to it by currently employed methods. A detailed study of the angular dependence of dosimeter response performed on a suitable phantom should aid in eliminating such inadequate dosimeters from practical use. PMID- 3350665 TI - Preparation and analysis of high-quality spiked soil standards. PMID- 3350666 TI - Early induction of leukemia (malignant lymphoma) in mice by protracted low alpha doses. PMID- 3350667 TI - Use of gypsum drywall as shielding material for mammography. PMID- 3350668 TI - Determining radiation exposure from nuclear accidents and atomic tests using dental enamel. PMID- 3350669 TI - Radiation hormesis and radiation cancer risk. PMID- 3350670 TI - Therapeutic aspects of health visiting. PMID- 3350671 TI - Health visitor support groups. PMID- 3350672 TI - Rubella immunisation: serological status and attitudes of pregnant women. PMID- 3350673 TI - Observations on an outbreak of meningitis. PMID- 3350674 TI - Parentcraft classes with Bengali mothers. PMID- 3350676 TI - Hypothermia in the elderly. PMID- 3350675 TI - Changes to Social Security in 1988. PMID- 3350677 TI - Providing open hearing clinics in a rural area of Cambridgeshire. PMID- 3350678 TI - No solace in the Social Fund. PMID- 3350679 TI - Use of fiber-optic pressure transducer for intracranial pressure measurements: a preliminary report. AB - Invasive monitoring of intracranial pressure (ICP) is becoming the standard of care for management of acute neurologic and neurosurgical patients. As a result of improved fiber-optic technology, a new disposable 4 French fiber-optic transducer-tipped catheter (FTC) has been introduced for facilitating measurement of intracranial pressure. Placement of the FTC can be intraventricular, subarachnoid, subdural, or intraparenchymal. Sensitivity and linearity of each catheter are manufacturer calibrated and not adjustable. Zero or atmospheric balance is done only once before insertion. Because the transducer is the catheter tip, no leveling to an anatomic point is necessary. The system appears to eliminate some of the difficulties inherent in fluid-filled catheter monitoring. In clinical trials, the comparison of FTC with subdural and ventriculostomy waveforms and pressures showed essentially no difference. Pressure recordings tracked well except during transient periods of increased ICP, when FTC showed higher peak pressures. Use of the FTC requires education regarding placement and maintenance techniques. Although staff experience with the catheter can practically eliminate the problem, the FTC catheters need special handling because of potential for fiber breakage. PMID- 3350680 TI - Assessment of physiologic instruments. AB - Nursing researchers are advised to consider the reliability and validity of psychologic instruments used in research; however, evaluation of physiologic, or clinical, instruments is not always given the same attention. Reliability and validity issues related to physiologic measures will be discussed. Terms commonly used for the evaluation of physiologic instruments, such as "accuracy," "precision," and "sensitivity," will be explained, with parallels drawn to traditional measurement terms. Sources of potential measurement error, such as environment, user, subject, machine, and interpretation error, will be explained and specific examples given from cardiopulmonary nursing research. PMID- 3350681 TI - Burned adolescents' descriptions of their coping strategies. AB - In an effort to describe adolescents' coping strategies after burns, eight postburn adolescents were interviewed. Their physical changes and their self described behaviors and responses to changes in appearance, function, and potential are delineated. With the use of Lazarus' coping paradigm, mechanisms described by subjects were classified as problem focused or emotion focused. Comparison is made with coping mechanisms previously identified in adults. Subjects' problem-focused adjustments included the institution of comfort and therapeutic measures, the resumption of preburn style of dress, varied verbal responses to questioning and staring, the redirection of career goals, and adjustments to phobic neurosis. Emotion-focused adjustments included anger, acceptance of limitations, anticipation of ridicule or rejection, decreased focus on physical changes, a sense of loss, boredom with burns and their sequelae, and various defenses such as rationalization, denial, intellectualization, and humor. Identification of specific physical changes and responses permits the nurse to plan interventions and to provide anticipatory guidance accordingly. PMID- 3350682 TI - Relationship between nurses' assessments of perfusion and toe temperature in pediatric patients with cardiovascular disease. AB - This descriptive study reports on 17 children who had undergone open-heart surgery. The children were assessed for 6 hours after surgery and once at 18 hours after operation to determine relationship between two scales assessing peripheral perfusion and the temperature of the great toe. There were 119 individual assessments. The scales used to assess the quality of peripheral pulses, extremity warmth, and capillary refill were (1) those representative of assessment scales used in common nursing practice and (2) more specific scales that attempt to "quantify" the qualitative assessment of peripheral perfusion. The more specific set of scales was used by "trained observers," with the bedside nurse using the nurses' scales. Results demonstrated that both sets of scales and observers were accurate in assessing peripheral perfusion as measured by the actual toe temperature. Analyses revealed which scales were better than others, and a method of assessing peripheral perfusion that includes the best components of all scales is suggested. PMID- 3350683 TI - Diagnostic accuracy of fever as a measure of postoperative pulmonary complications. AB - Various prevalence rates have been estimated for pulmonary complications after abdominal surgery, and fever has been thought to be a diagnostic indicator. This study quantifies the diagnostic accuracy of fever as a measure of postoperative pulmonary complications and includes the sensitivity, specificity, and positive and negative predictive values. Assessments using fever and chest x-ray film were determined for 270 patients after elective intra-abdominal surgery in three hospitals with six practicing surgeons in a Southern Ontario city. With use of reliable chest x-ray reports indicating lung pathologic findings as positive for pulmonary complication, the prevalence of a positive finding was 57%. The prevalence of a fever (temperature greater than or equal to 38 degrees C) was 40%. The sensitivity and negative predictive value of fever were slightly below 50%, and the specificity and positive predictive value of fever was 68% and 66% respectively. Fever was an accurate indicator of x-ray evidence of atelectasis in only 56% of the subjects. Therefore, neither the presence nor the absence of fever can assure clinicians of the presence or absence of a postoperative pathologic pulmonary complication such as atelectasis. PMID- 3350684 TI - Relationship of hope and stress after myocardial infarction. AB - This study examines the relationship of perceived stress associated with an acute myocardial infarction and the patient's perception of hope in the coronary care unit. The subjects, 40 to 70 years of age, had experienced a first myocardial infarction. The research design was a nonexperimental, retrospective study using a convenience sample. The highest percentages of perceived stress were associated with the factors of unfamiliar surroundings and missing one's spouse. The sample population had high hopefulness scores for the factors of feelings about the future and personal motivation but ambivalent scores associated with future expectancies. Correlation of scale scores revealed no statistical relationship between perceived hope and stress for this sample population. Clinical applications are multiple. Nursing interventions to reduce stress should include an in-depth orientation to the environment and should allow for frequent contact with one's spouse. Denial must be considered as a basis for a high degree of hope perception during the first 7 days after infarction. PMID- 3350685 TI - Family care in the coronary care unit: an analysis of clinical nurse specialist intervention. AB - A sudden and life-threatening illness requiring hospitalization and admission to the coronary care unit (CCU) can result in serious disorganization for the patient's family. This disorganization can become obvious to staff when family members are too anxious to hear important information about the patient or when families are unable to make decisions about the patient's treatment or disposition. Although CCU care is highly technical, it is not exclusively technical. Patients and their families need care that is considerate of the family group. In a case report, the Lazarus stress and coping framework is used to assess, intervene in, and evaluate care given to one family during an admission of a family member to the CCU. Although this framework is individually oriented and is particularly dependent on individual cognition, it proved useful for work with the described family. PMID- 3350686 TI - Outpatient rehabilitative training in patients with cardiovascular disease: emphasis on training method. AB - As our ability to evaluate cardiovascular patients expands and direct oxygen consumption measurements are available, exercise prescriptions can be better individualized for each patient. By using basic principles of frequency and duration and specifically basing intensity and progression on percent of maximum oxygen consumption, protocols using various modes of exercise may be defined so that each patient entering cardiovascular training programs will gradually progress. This methodology discussion presents concise progressions for both phase II monitored and phase II nonmonitored medically supervised exercise training. The phase II monitored protocol consists of levels 1 through 6 and is designed to be completed within a minimum of six 1-hour sessions. The phase II nonmonitored protocol consists of levels 7 through 12 and is designed to be completed within 12 weeks. The ultimate goal is for each patient to safely progress to a training level that can be maintained safely and effectively by the patient. A total of 192 patients enrolled in our phase II programs have safely completed both components and are in long-term maintenance programs. PMID- 3350687 TI - Streptococcus mutans endocarditis: report of three cases and review of the literature. AB - Our findings indicate that S. mutans endocarditis is capable of causing significant morbidity and mortality, as exemplified by the prolonged and complicated hospital course of our patients and the ultimate death of one of them. S. mutans endocarditis is probably underreported because most clinical laboratories do not speciate the viridans streptococci. Isolates of S. mutans should be tested for tolerance that would require the addition of an aminoglycoside to the penicillin regimen. Our experience agrees with the literature and indicates that S. mutans is primarily a pathogen in elderly patients with heart disease and may be associated with IHSS. PMID- 3350688 TI - Acquired immunodeficiency syndrome and refusal to provide care. PMID- 3350689 TI - An acute cardiovascular event in an endurance-trained athlete. AB - In athletes, symptoms and electrocardiographic patterns may mimic an acute coronary event. In addition, endurance athletes show significantly elevated heart specific serum CK-MB enzyme activity in the first week after athletic competition. Also, cellular control of the CK-MB enzyme is consistently elevated in skeletal muscles of trained endurance athletes. Thus, all three criteria used in diagnosis of acute myocardial infarction may be found in the athlete's heart. Awareness of these potential findings in athletes as "heart patients" and curtail unnecessary hospitalizations. PMID- 3350690 TI - Qualitative research designs in the critical care setting: review and application. PMID- 3350691 TI - Paramagnetic metal complexes as MRI contrast agents. PMID- 3350692 TI - Hydration states of lanthanide complexes. PMID- 3350693 TI - Radiographic contrast media, function and future reassessed. PMID- 3350694 TI - Considerations involving paramagnetic coordination compounds as useful NMR contrast agents. PMID- 3350695 TI - Albumin binding of paramagnetic hepatobiliary contrast agents: enhancement of outer sphere relaxivity. PMID- 3350696 TI - Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies. PMID- 3350697 TI - Highly stable lanthanide macrocyclic complexes: in search of new contrast agents for NMR imaging. AB - This paper presents the views of a coordination chemist on the synthesis and the properties of new contrast agents containing gadolinium. Attention is drawn to various macrocyclic complexes such as the polyaza polycarboxylic chelates, the cryptates as well as compounds obtained by template synthesis. The structural factors influencing the kinetic and thermodynamic stability of the gadolinium complexes are discussed with special emphasis on the polyaza polycarboxylic derivatives. Some of the macrocyclic complexes under investigation are more stable than Gd-DTPA. PMID- 3350698 TI - Genetic variability in white-tailed deer. AB - Genetic variability at 36 loci was studied in white-tailed deer (Odocoileus virginianus) populations, on the Savannah River Plant (SRP) in South Carolina. Mean multilocus heterozygosity (H), percentage of polymorphic loci (P) and average number of alleles per locus (A) for white-tailed deer were calculated and compared with values for white-tailed deer from several locations (SRP deer: H = 9.9 per cent, P0.05 = 30.6 per cent, A = 1.89; white-tailed deer overall: H = 10.4 per cent, P0.05 = 32.3 per cent, A = 1.94). Frequency distributions for single locus heterozygosity values (h) and the number of alleles per locus for white-tailed deer were found to be significantly different from those of mammals in general. Analysis of single-locus data based on quaternary structure and functional groups of proteins failed to demonstrate expected differences as predicted from the literature. White-tailed deer have a high level of heterozygosity, but they do not exhibit many of the life history and environmental characteristics associated with high heterozygosity in other animals. PMID- 3350699 TI - An examination of the role of chiasma frequency in the genetic system of marsupials. AB - Chiasma frequencies have been collected from males of 33 species of marsupial, varying widely with respect to size, reproduction and development. Correlation analyses show that species with lower levels of recombination are smaller, have larger litters and develop more quickly. Two indices of recombination level were considered: Darlington's Recombination Index, and the Excess Chiasma frequency (chiasmata above one per bivalent). The EC is in general more strongly correlated than RI with aspects of life history. It is suggested that EC levels have evolved due to the effects of EC on recombination, but that chromosome number has evolved independently. PMID- 3350700 TI - [Unilateral patulous eustachian tube with tinnitus, inner ear damage, vertigo and sudden deafness--collagen injection]. AB - In elderly patients an unilateral sensorineural hearing loss is frequently associated with a relatively more patent eustachian tube on the involved side. A simple method of investigation is observation under the operating microscope during tubal inflation by the patient. In right-handed patients the abnormally patent tube most often lay on the left side. Powerful self inflation in these patients induces acute hearing loss and vertigo. Acute hearing loss is commoner on the left side. The air bone gap is greater at higher frequencies due to mobility of the stapes, loosening of the incudal joints and the tympanic membrane. In contrast the air bone gap is greater at lower frequencies in otosclerosis or malleus head ankylosis. Minor degrees improve after self inflation is prohibited. In most patients with abnormally patent eustachian tubes further therapy is not necessary after the patient has received precise advice. In only about 20% of the cases is the patient disturbed by a feeling of fullness in the ear, autophony and tinnitus. After stabilisation of weight and blood pressure, a septoplasty with correction of the posterior turbinates may reduce the exspiratory resistance. The most drastic treatment is a collagen injection around the tube. Patients with depression should be treated appropriately. PMID- 3350701 TI - [Clinical aspects and prognosis of paranasal sinus tumors with special reference to their etiology]. AB - Sixty-one patients operated on for malignant paranasal sinus tumours were investigated to elucidate the incidence and route of metastasis; survival rate, incidence of recurrent tumours, sex distribution etc. as well as possible exogenous causative factors. Adenocarcinomas have a better prognosis in women than in men and sometimes show local recurrences even 10 years and more after primary operation. Tumours of the paranasal sinuses often produce primarily hematogeneous distant metastases, with a fatal outcome. Occupational carcinogenic influence of wood dust seems very likely. PMID- 3350702 TI - [Otogenic brain abscess and middle ear cancer]. AB - An uncommon case is reported in which both a brain abscess and a carcinoma of the middle ear were diagnosed at the same time. Before the histology was known, a cholesteatoma was thought to be the cause of the brain abscess. The difficulties in the differential diagnosis are discussed. PMID- 3350703 TI - Morphometric analysis of the human corpus callosum and anterior commissure. AB - The cross-sectional areas of the corpus callosum (CC) and anterior commissure (AC) were determined by computer-assisted morphometry in normal human brains obtained at autopsy. In addition, the shape of each CC was examined qualitatively by three "blind" observers. A two-fold variation was observed in the cross sectional area of the CC. Surprisingly, callosal cross-sectional area was not significantly related to brain weight. Moreover, contrary to recent reports, neither simple inspection nor morphometry revealed structural variation related to sex. A striking, seven-fold, variation was observed in the cross-sectional area of the AC. However, AC cross-sectional area was not related either to brain weight or CC cross-sectional area. A trend toward sexual dimorphism in AC cross sectional area was observed, with males having the larger AC's. Since the interhemispheric commissures are composed, to a large extent, of fibers that link the various cortical areas of the two hemispheres, these observations suggest that variation in the cross-sectional area of the interhemispheric commissures is not simply related to brain weight or sex but, rather, reflects a similar degree of variation in some aspect of cortical structure. PMID- 3350704 TI - An outline of human neuroethology. AB - Neuroethology is concerned with the analysis of neural substrates and mechanisms that underlie invariant forms of species-typical behavior. The aim of this outline is to delineate in an evolutionary perspective some specific human functional brain states and mechanisms which form the foundation of homo-typical behavior and experience. Dreaming, as one example, is considered to belong to the universals of human experience. Another example is the repertoire of human emotion and mental phenomena evoked by the electrical stimulation of the human limbic system. The expression of emotions by vocal behavior gains momentum in man and is based on certain transformations of the CNS that were fundamental for the emergence of speech. The phonemes in speech are the species-typical articulatory gestures for which a special decoding device is required. This innate mechanism may have features in common with the vocal signal decoding mechanism of subhuman primates. PMID- 3350705 TI - Decreased numbers of dendritic spines on cortical pyramidal neurons in dementia. A quantitative Golgi study on biopsy samples. AB - The number of dendritic spines on the apical dendrites of layer III pyramidal cells was counted in cerebral biopsies, processed in part according to the rapid Golgi method, which had been performed for diagnostic purposes on patients suffering from dementia of different origins. The samples were from cases affected by Alzheimer's disease (3 patients), Parkinson's disease and dementia (1 patient), Creutzfeldt-Jacob disease (4 patients), Pick's disease (1 patient) and dementia paralytica (1 patient). Spines were counted on consecutive segments of the apical dendrite along the 500-microns proximal region from the cell body. A significant decrease in the number of spines was observed in almost every segment of the apical dendrite in demented patients when compared with similar measurements carried out in age-matched controls (p less than 0.01-0.001); Mann Whitney U-test. Decreased numbers of dendritic spines may result in reduced inputs on cortical neurons and may be a consistent morphological substrate for the impaired mental status in cortical dementia. PMID- 3350706 TI - Numerical estimates of GABA immunoreactive neurons in the human lateral geniculate nucleus in the prenatal period. AB - Quantitative analysis has been performed on Nissl stained and gamma-aminobutyric acid (GABA) immunoreactive neurons in the lateral geniculate nucleus (LGN) of human fetuses ranging from 8 to 37 weeks of gestation. Total cell density in the LGN increases from 8 to 12 weeks of gestation with a subsequent decline continuously up to 37 weeks. No GABA immunoreactive neurons are visualized in the LGN of 8 and 12 weeks fetuses. At 15-16 weeks of gestation 1% of neurons are immunostained. A peak rise is seen to occur at 17 weeks when 16% cells are GABA immunopositive. However, at 19 weeks there is an equally sharp decline in the percentage of GABA neurons to 4%. Subsequently, with the continued reduction in overall numerical density the percentage of GABA neurons remains relatively constant but rises again to 5% at 26 weeks. On making quantitative estimations of numerical density and percentage of GABA neurons separately for the prospective magno- and parvocellular regions in the early age periods from 15-16 to 21 weeks as well as at 22-23 weeks, when magnocellular laminae begin to segregate, and at 26 weeks when distinct laminae are present, it is observed that the magnocellular regions have a higher density and percentage of GABA neurons at all the gestational ages in comparison to the parvocellular region. With increasing gestational age, non-GABA neurons gradually increase in size with marked growth of magnocellular neurons at 26 weeks. The GABA neurons, on the other hand, have an almost constant size up to 19 weeks and start growing from 21 weeks onwards. The GABA neurons tend to be larger in the magno- than in parvocellular regions at all gestational ages studied. PMID- 3350707 TI - The visually evoked potential in response to vernier offsets in infants. AB - The visually evoked potential (VEP) was recorded from infants (1 month 25 days to 13 months 3 days) in response to vernier offsets, motion displacements, and a stationary stimulus which served as a noise control. The records were analyzed by five masked adult observers familiar with VEP recordings using a signal detection method. The results suggest that a VEP can be recorded from infants in response to a vernier offset and the response resembles that obtained from adults tested with the same procedure. However, unlike adults, infants also showed a response to a motion displacement of the same magnitude suggesting that infants may not show the same specificity for the break in colinearity characteristic of the adult VEP. PMID- 3350708 TI - The H reflex recovery curve reinvestigated: low-intensity conditioning stimulation and nerve compression disclose differential effects of presumed group Ia fibres in man. AB - The recovery curve of the soleus H reflex, evoked by stimulation of the tibial nerve in the popliteal fossa, was studied by applying an electrical conditioning stimulus to the inferior soleus nerve. Under these conditions a long-latency facilitatory phase could be superimposed on a long-lasting inhibition, the excitability cycle being therefore similar to that obtained by means of a paired shock to the tibial nerve. In order to identify the afferent fibres responsible for the effects observed, various conditioning stimulus strengths and nerve compression were used. A low-intensity stimulus induced only a facilitatory phase, while the inhibition promptly ensued on increasing stimulus strength, which remained however subliminal for activation of group II fibres. During calf compression exerted by a sphygmomanometer cuff placed between the conditioning and test stimuli, the facilitatory effects disappeared within 10 to 15 min, and the inhibitory ones disappeared within 25 to 30 min from the onset of compression. Tonic voluntary contraction enhanced both the inhibition and the facilitation. In a subject with complete spinal section, both inhibitory and facilitatory phases could be demonstrated on low-intensity stimulation. The present data, and previous results of ours, allow the following conclusions. (1) Facilitation and inhibition are produced by fibres likely belonging to group Ia spindle afferents. (2) Both effects are of spinal origin. (3) The spinal circuits mediating the effects may be modulated by descending commands. (4) The facilitation is sustained by tonic supraspinal influences while the inhibition is independent of it. Arguments are proposed against the hypotheses that the inhibition be due to transmitter depletion or to presynaptic mechanisms. PMID- 3350709 TI - Neurofunctional assessment of early phases of Alzheimer's disease: a preliminary note on hemispheric EEG characteristics during cognitive tasks. AB - EEG characteristics, in terms of power distribution in 1-4, 4-6, 6-8, 8-10, 10 13, 13-18, 18-30 Hz frequency bands were evaluated in six putative non-medicated male Alzheimer patients. The latter were compared with six age and sex-matched normal controls during both resting conditions and tactile identification tasks specific for the left and right hemispheres. The result indicate a significant difference in the power of the 8-10 frequency band between the two groups and a significant hypovariability in the 6-8 and 8-10 bands during tactile tasks: Alzheimer patients showed reduced power and, also, where less reactive, no differences between the left and right hemispheres having appeared. These findings seem to confirm the specificity of EEG modifications in Alzheimer's disease, even in the very early phases of the pathological process. Possible implications are discussed in the light of some biochemical hypotheses. PMID- 3350710 TI - Event-related EEG-spectra in a concept formation task. AB - Event-related spectra of short EEG epochs were investigated in a concept formation paradigm. In this task, subjects had to learn to transform letters into Morse codes. Related to a resting state, cognitive performance in this learning task was characterized (i) by an increased mean power density (MPD) within the Theta frequency band (theta) in recordings over the frontal lobes and (ii) by a reduced Alpha (alpha) MPD in all recording sites. The performance-related increase of the theta-MPD, as obtained in left frontolateral and frontomedial recordings, separated (i) the learning task from an appropriate control and (ii) a group of successful learners from a group which performed less efficiently. MPDs of the alpha- and the delta-(Delta) frequency band did not differ between tasks and groups. A consistent finding in the learning tasks was a temporal dissociation of performance-related alpha-attenuation between parietal and frontal recordings: in the period preceding the presentation of the informative stimuli, the alpha-rhythm is attenuated especially at parietal recordings, whereas in frontal recordings, alpha-attenuation accompanied information processing and response selection. PMID- 3350711 TI - Speaking out on homosexual health hazards beyond AIDS. PMID- 3350712 TI - Preventive medicine: osteoporosis. PMID- 3350713 TI - Segmental definition: Part II. Application of an indirect method in osteopathic manipulative treatment. PMID- 3350714 TI - Familial cancers. PMID- 3350716 TI - Ear disorders in children. PMID- 3350715 TI - AIDS-related psychosocial issues for the patient and physician. PMID- 3350717 TI - Analysis of pelvic tumor control and impact on survival in carcinoma of the uterine cervix treated with radiation therapy alone. AB - A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960 1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The 10-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25%. Many of the deaths were due to intercurrent disease. Thus, the 10-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with the following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30% for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3350718 TI - Primary radiotherapy of squamous cell carcinoma of the oropharynx and pharyngolarynx: tentative multivariate modelling system to predict the radiocurability of neck nodes. AB - In a series of 1251 cases of squamous cell carcinomas of oropharynx and pharyngolarynx with clinically positive neck and treated primarily by radiation therapy a determinate group of 798 cases remained eligible for a multivariate analysis of the prognostic factors related to the regional outcome. Node size (p less than 0.0001), node fixity (p = 0.016) and T stage (p = 0.02) were the significant pretreatment factors independently predictive of neck node control. when regarding the treatment modalities in this determinate group of patients who received tumor doses of at least 55 Gy, only the treatment duration was found to be predictive (p = 0.002). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various groups of patients. The predictive accuracy of the equation was assessed by the log-rank test significance levels. The model may help to select, in many clinical situations, the appropriate approach of the management of metastatic neck disease, either by definitive radiation therapy or by combined modalities. PMID- 3350719 TI - Hyperfractionation for head and neck cancer. AB - Between March 1978 and April 1984, 144 patients with 148 moderately advanced to advanced primary squamous cell carcinomas of the head and neck received treatment with curative intent with twice-a-day irradiation (120 cGy/fraction, 4-6 hour interfraction interval). Eighty-eight percent of the patients had AJCC Stage III IV cancers. One hundred and thirty-two patients received irradiation alone to the primary site with or without radical neck dissection, with surgery reserved for salvage. The total doses administered were 7440-7920 cGy in the majority of instances. In 19 patients with oropharyngeal lesions, a 1000-1500 cGy radium needle boost was added after the basic dose. Twelve patients received preoperative irradiation (5040-6000 cGy) followed by primary resection and radical neck dissection. Local control results following irradiation alone to total doses of greater than 7000 cGy with minimum 2-year follow-up were 25/31 (81%), 38/50 (76%), and 5/25 (20%) for T2, T3, and T4 cancers, respectively. Local control rates did not correlate well with total dose. Local control following preoperative irradiation plus primary resection was obtained in 4 of 5 T3 and 2 of 3 T4 primary lesions. The 5-year actuarial rates of neck control were 100% for N0 (45 patients), 90% for N1 (25 patients), 77% for N2 (23 patients), 50% for N3A (9 patients), and 70% for N3B (42 patients). The 5-year actuarial rates of continuous disease control above the clavicles were 73% for Stage III, 64% for Stage IVA, and 32% for Stage IVB. The actuarial 4-year rate of continuous disease control above the clavicles was 78% for Stage II. For patients whose disease was controlled above the clavicles, distant metastases developed in 4% of patients with Stage II-III disease and in 18% of patients with Stage IV disease. Radiation complications following irradiation alone to the primary site correlated with total dose. Complications of planned neck dissection(s) were acceptable. Complications of salvage surgery at the primary site were similar to those seen in patients treated once a day. The actuarial 5-year survival rates, according to modified AJCC stage, were 59% for Stage III, 37% for Stage IVA, and 23% for Stage IVB. The actuarial 4-year survival rate for Stage II was 69%. Compared to historical control groups treated with once-a-day, continuous-course irradiation at our institution, twice-a-day treatment has produced local control results that are higher by 10-15 percentage points. PMID- 3350720 TI - Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy. AB - Conservation breast treatment is of particular interest to young women, but whether saving the breast carries a penalty in shorter survival or local-regional recurrent disease has not been well-established. At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, 1161 patients treated prior to 1983 with Stage I or II breast cancer were reviewed. Of these patients, 378 were treated with tumorectomy plus irradiation, and 783 were treated with radical or modified radical mastectomy. The two patient groups were compared relative to local-regional disease recurrence and overall and disease-free survivals. Local recurrences in the breast appear to be more frequent in patients less than or equal to 35 years of age treated with tumorectomy and irradiation than in patients older than 35 years, but in patients aged less than or equal to 50 or greater than 50 or less than or equal to 35 or greater than 35 years, there was no significant statistical difference between tumorectomy and irradiation or mastectomy nor was there a difference in disease-free survival. Overall survival rates favored patients treated by tumorectomy and irradiation. PMID- 3350721 TI - The efficacy of delayed radiotherapy for locoregionally recurrent postmastectomy breast cancer. AB - Using the results from a randomized controlled trial of patients with operable breast cancer (aimed at assessing the need for immediate postmastectomy radiotherapy in patients with no histological evidence of nodal involvement on subpectoral node biopsy), it has been possible to study the effectiveness of salvage radiotherapy for recurrences in the group of patients who had not received postoperative radiotherapy. While only 1 of 43 patients (2.3%) showed progressive disease, there was a further in-field relapse in 16 of the remaining 42 patients (38%). Four of these patients were salvaged by systemic therapy. Ultimately, therefore, there was failure of delayed radiotherapy for locoregional control in 30% of patients. (However, the overall locoregional control in both arms of the trial was identical). PMID- 3350722 TI - Conservative treatment of early breast cancer. AB - At our Institution, the treatment policy for early carcinoma of the breast (T1-2, NO, AJC) is lumpectomy followed by radiotherapy to the breast and peripheral lymphatics. From October 1976 until December 1982, 171 patients have been admitted and treated. Radiotherapy was administered with 60 Co, 5.000 cGy in 5 weeks to the breast and lymphatics plus a boost to the scar giving q.s.p. 6.400 cGy at maximum tumor depth. With a minimum follow-up of 3 years and a median follow-up of 61.7 months the locoregional control was 94.2% and survival at 8 years with no evidence of disease (NED) was 77.2% with an overall survival rate of 90%. No difference in NED survival rate was found between Stage I and II. There was a tendency to better survival rate in those patients older than 50 years and also for post menopausal patients, however the difference did not reach statistical significance (66.7% NED survival at 8 years for premenopausal and 81.8% NED survival for post menopausal, also at 8 years, p = 0.056 Gehan). The time elapsed between surgery and radiation therapy (between 1 and 2 months) was found to be nonsignificant. Only 1 out of 171 patients had axillary dissection. The importance or lack of it, is discussed. PMID- 3350723 TI - Management of elderly patients with primary breast cancer. AB - From 1974 through 1983, three hundred forty-three patients aged 70 years or older at diagnosis received comprehensive post-operative radiation therapy for localized (Stage I-III) breast cancer following surgical procedures ranging from incisional biopsies to classical radical mastectomy. The 5- and 10-year overall survival rates for this series of elderly patients are 67% and 33%. The respective disease-free survival rates are 67% and 42%. Over one-half of these women were treated by less than total mastectomy. No differences were seen in survival, disease-free survival, or local regional control rates comparing similarly staged patients treated by radical mastectomy, modified radical mastectomy, or tylectomy. Complications were few and seen primarily in those patients subjected to axillary dissection prior to irradiation. Long term survival appears to be achievable in the majority of elderly patients with regionally confined disease at presentation and aggressive treatment with curative intent is warranted. These elderly patients are often poor candidates for radical surgery. In this patient population, conservative surgery with post operative radiation therapy is well tolerated and provides equivalent results to more radical surgical procedures. PMID- 3350725 TI - The role of radiation therapy in stages A2 and B adenocarcinoma of the prostate. AB - Between 1965 and 1982 definitive external beam radiation therapy was given to 114 patients with clinically Staged A2 (32 patients) and B (82 patients) adenocarcinoma of the prostate. These patients were not considered to be surgical candidates because of age, comorbidity or disease extent, or because they had refused surgery. Total prostatic doses ranged from 60 to 70 Gy. For 90 surviving patients, follow-up duration ranged from 32 to 188 months with a median of 5 years. The 5- and 10-year uncorrected survival rates for all patients, which were 89% and 68% respectively, were no different from the survival expectation of age matched men in the general population. Disease-free survival rates at the same time periods were 89% and 86%. There were no significant differences in disease free survival between Stage A2 and Stage B. Four patients (3.5%) developed local recurrence. Bone metastases, which occurred in 9 of 11 treatment failures were the predominant cause of failure. An analysis of 11 potential prognostic factors was fruitless. Pelvic node irradiation did not improve the outcome. The incidence of complications was acceptable. Anorectal problems developed in 20% of patients and urinary manifestations occurred in 20%, and only 2 patients (1.8%) developed serious problems. We concluded that localized external beam high-energy radiation therapy provides excellent local control for disease limited to the prostate, with survival rates that rival those of radical surgery. PMID- 3350724 TI - Treatment of soft tissue sarcomas by preoperative irradiation and conservative surgical resection. AB - From 1970-1984, 114 patients with soft-tissue sarcomas received preoperative irradiation at U.T.M.D. Anderson Hospital. Two patients refused surgery and two had progressing disease and therefore did not proceed to surgery; in the remaining 110 patients, conservative surgical resections were performed 3-6 weeks following irradiation. Analysis of survival by histologic type, age, primary size, and histologic grade revealed a significant negative correlation with grade 3 and to a lesser extent to primary size greater than 15 cm. Eleven patients failed within the radiation portal for the primary, four in conjunction with distant metastases. Of the remaining seven, four were salvaged by further surgery for an ultimate primary-only failure rate of three. Distant metastasis occurred in 35 patients and was the major mechanism of treatment failure in this experience. Adjunctive chemotherapy was not used for the majority of patients and it remains to be seen if its routine employment in large, high-grade, lesions will diminish the deaths caused by distant metastases. PMID- 3350726 TI - Charged particle radiotherapy of selected tumors in the head and neck. AB - For selected tumors in some sites in the head and neck region, charged particles such as protons or helium, carbon, neon and silicon ions provide improved dose distributions, higher tumor doses, and an increased chance of local control and prolonged survival. In tumors with "radioresistant" histologies, slow growth kinetics and/or hypoxic cells, the high-LET component of neon or silicon ions may also offer and added potential for increased effect on tumors. Sixty-seven (67) evaluable patients with tumors in the head and neck region having a histology other than squamous carcinoma received partial or full treatment with charged particles at the University of California Lawrence Berkeley Laboratory. The tumor sites included base of skull or cervical spine, salivary glands, paranasal sinuses, nasopharynx, and miscellaneous sites such as lacrimal gland, soft tissues of the neck, or thyroid. Follow-up ranges from 1-9 years with a mean of 36 months and a median survival (Kaplan-Meier technique) of 50 months. The actuarial local control rate is 60% at 24 months post-treatment. Thirty-one (31) patients with squamous carcinoma of various sites in the head and neck have also been treated using charged particle irradiation; local control was lower (11 of 31 pts) and survival shorter (mean: 9 months) in this group of patients with advanced squamous carcinoma. PMID- 3350727 TI - Inadequacy of conventional computerized tomography scans for treatment planning of tangential breast (chest wall) fields. AB - The use of transverse tomography treatment-planning scans, which have to be taken in the exact treatment position of the patients, is essential for precision radiotherapy of breast cancer. Transverse tomography scans give all necessary informations for an optimal isodose distribution within the target volume for the individual patient, and maximal sparing of normal tissues (e.g. lung) is achieved. The exact topography of internal mammary nodes may also be incorporated in the planning scan with the help of lymphoscintigraphy. Conventional computerized tomography (CT) scanners have too small gantry openings (50-70 cm) to allow for proper positioning of the patients under treatment conditions. Using such treatment-planning scans for patients in the actual treatment position would cause an underdosage in excess of 5% within the target volume, when 60Co fields are used. Also, a much larger volume of normal tissues (mainly lung) would unnecessarily be irradiated. Treatment-planning scans obtained by TAT (transverse analog tomography) do not have the crucial positioning problems of conventional CT scanners and enable the precise transformation of a valid isodose distribution to each patient. In addition, positioning wedges (with adjustable wedge angles) may be placed under the patient to achieve the optimal treatment position. A useful alternative of TAT scanning for precise treatment planning of patients with breast cancer would be a CT scanner with a wide enough gantry opening to allow for any patient positioning under actual treatment conditions. PMID- 3350728 TI - Safety of adjunctive transvaginal beam therapy in the treatment of squamous cell carcinoma of the uterine cervix. AB - At The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1970 and 1980, 159 patients with bulky cervical cancers of FIGO Stages IB or II were treated with transvaginal orthovoltage radiotherapy (TVR) as an adjunct to standard external beam megavoltage irradiation and brachytherapy. The majority received 10 or 15 Gy air dose in 2-3 fractions using 125-250 kVp X rays. The dose from TVR was ignored in subsequent standard treatment planning. The absolute 5-year local control and survival rates were 82 and 83%, respectively. A total of 9 patients (5.7%) developed serious treatment complications that were significantly related to performance of a staging lymphadenectomy prior to radiotherapy and to an external beam pelvic dose of 50 +/- 0.5 Gy versus 40 +/- 0.5 Gy. The risk complications was not related to the dose of TVR or brachytherapy within the ranges used. Provided patients are properly selected and appropriate technical precautions are exercised, TVR is a safe technique. It is effective in controlling bleeding and shrinking large exophytic tumors, and very likely contributes to improved tumor control by facilitating optimal geometry for intracavitary therapy. PMID- 3350729 TI - Hyperfractionated split-course whole abdominal radiotherapy for ovarian carcinoma: tolerance and toxicity. AB - Whole abdominal irradiation after chemotherapy and second look laparotomy for advanced ovarian carcinoma is poorly tolerated because of hematologic toxicity that frequently necessitates interruption or abandonment of treatment. A new treatment strategy using a hyperfractionated split course schedule to deliver a total of 30 Gy in 30 fractions over 6 weeks was designed in an attempt to overcome this problem, while not compromising the tolerance of late reacting normal tissues. Of 23 patients treated between August 1984 and June 1986, only one failed to complete therapy as scheduled. Six patients with gross residual disease also received a limited field boost of 15 Gy in 15 fractions after completion of treatment to the whole abdomen. None of these six patients achieved disease control, and five required surgery for intestinal obstruction with pathologic evidence of radiation bowel injury. Of the 17 patients who received no boost, five developed gut obstructions associated with tumor recurrence and not attributable to irradiation. We conclude that whole abdominal irradiation using the hyperfractionated split course schedule without a boost is safe and feasible but its therapeutic efficacy appears confined to subsets of patients with no visible residual disease at the time of second look laparotomy, or in whom all visible residual tumor can be resected. PMID- 3350730 TI - Primary squamous cell carcinoma of the vagina treated by radiotherapy: a failures analysis--the M. D. Anderson Hospital experience 1955-1982. AB - The retrospective study concerns 167 patients with primary squamous cell carcinoma of the vagina treated at The University of Texas M. D. Anderson Hospital and Tumor Institute between January 1955 and December 1982. Of these 167 patients, 162 were evaluable and 5 were lost to follow-up. For small tumors, localized treatment by brachytherapy alone, transvaginal irradiation with 125 to 250 kV alone or in combination with brachytherapy, was mainly used, with emphasis on use of colpostats and transvaginal irradiation for tumors of the upper half of the vagina and interstitial (with radium needles or, later, afterloaded stainless steel guides with iridium wires) for the lower half. For medium-size tumors, local treatment was combined with external irradiation, mainly using conservative size fields. For the majority of larger tumors or when the anatomy was distorted, external irradiation alone was used, also with portals of conservative size. Failures were analyzed in relation to FIGO (International Federation of Obstetrics and Gynecology) staging, tumor location, and modality of treatment. As expected, central failures were higher in Stage III disease (9 of 38 patients, 24%) but also uncomfortably high for Stage I patients (13 of 71 patients, 18%) treated locally or with external and local irradiation. The incidence of central treatment failures in tumors of the lower vagina (13/51 patients, 25%) was somewhat higher than for tumors located in the upper vagina (13/85 patients, 15%), but the percentage of large tumors in the lower vagina was 53% compared with 31% in the upper vagina. Severe complications were related to high doses of irradiation alone or in combination with aggressive surgery, and to pelvic inflammatory disease. PMID- 3350731 TI - Treatment volume and tissue tolerance. AB - Hypotheses regarding tissue organization and radiation response were described and, on the basis of simple modeling, tentative conclusions were drawn regarding the influence on "tolerance" doses of tissue organization and the volume of an organ irradiated. (1) A functional subunit (FSU) may be defined structurally (e.g. as in a nephron), or only functionally, as the largest unit of cells capable of being regenerated from a surviving clonogenic cell without loss of the specified function. (2) Functional subunits may be arranged in parallel or in series: in parallel they give rise to graded dose responses, whereas in series, they give rise to threshold binary, or quantum responses. (3) Tolerance doses are a function of the number and radiosensitivity of target cells in an FSU, tissue organization and the functional reserve (i.e. the proportion of functional subunits necessary for adequate organ function). (4) An influence of treatment volume on "tolerance" doses is more likely to depend upon tissue organization than upon differences in cellular radiosensitivity. (5) The volume of tissue irradiated would be expected to be irrelevant to the "tolerance" of tissues showing a graded dose response (e.g. skin desquamation), except when the injury becomes severe, when tolerance for a large severe wound is likely to be less than for a small volume of injury, for non-radiobiological reasons. (6) Tissues with FSU's arranged in series, for example, spinal cord or peritoneal sheath along small bowel, should show a threshold-binary response. Sigmoid dose response curves should have a lower threshold and be steeper the larger the treatment volume. The effect of increase in volume is greatest with changes in small volumes: once a large number of FSU's are being irradiated, a further increase in volume has little effect on the position or slope of the probability curve for such complications. (7) Because their sigmoid dose-response curves are step, threshold-binary tissues are sensitive to small increases in "biologically effective" dose. For example, when the spinal cord is treated with large dose fractions the biological effectiveness per unit of dose increases sharply. Thus, using a large volume together with large dose fractions, as could happen in palliative prescriptions, could augment the danger of myelitis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3350732 TI - Potential for improvement in radiation therapy. AB - A successful strategy for improving the efficacy of radiation therapy has been to improve dose distribution, that is, reduce treatment volume toward target volume. This is so as the smaller treatment volume has permitted a higher dose to the target (hence a high tumor control probability) and a lesser volume of non-target tissues being irradiated (consequently a reduced frequency and severity of treatment related morbidity). There are in place several important means for further improvements in dose distributions. These include: (a) 3D graphic reconstruction of the affected part with definition of the position of the tumor vis-a-vis the adjacent normal structures; (b) explicit inclusion in the treatment plan of the uncertainty band around each isodose contour; (c) on-line contrast enhanced visual monitoring of the target tissue during the individual treatment session; (d) gating of treatment so as to reduce the impact of patient motion on the needed treatment volume; (e) use of computer control systems to execute the treatment; and (f) use of treatment methods which achieve a reduced treatment volume. In an examination for sites for which treatment volumes might be decreased by a substantial factor we have compared treatment volumes for radical surgical and radiation therapy. Results are presented for carcinomas of the cervix (Stage IB), breast (Stage II), floor of mouth (Stage II). We describe a system developed here for on-line visual monitoring of the tissues covered by the treatment field. Brief descriptions are given of results of low LET charged particle radiation therapy and of intraoperative electron beam therapy. Also, the program developed here to use computer graphic techniques to display tumor and normal structures and isodose countours with uncertainty bands around each contour is mentioned. PMID- 3350733 TI - Evaluation of unplanned interruptions in radiotherapy treatment schedules. AB - One of the major radiobiological interests has been to maximize the effectiveness of the time-dose relationship in the clinical setting. Current explorations include altered fractionation schedules, multiple daily fractions and hypofractionation. Patient compliance to standard radiotherapy treatment schedules is taken for granted. To evaluate the true rate of compliance, the charts of all new patients treated from July 1, 1984 through June 30, 1985 were reviewed. The overall incidence of unplanned interruptions was 54% (361/668). The frequency of interruptions is significantly higher in patients treated to the primary site as compared to those treated for metastasis (59.8% and 35.6% respectively). The duration of the interruptions varied: 12.7% of the patients missed only 1 day, 25% missed 2 to 5 days, 38% had interruptions totalling 6-15 days, and in 24% the total exceeded 15 days. The most frequent cause of the unplanned interruptions was a rest resulting from unusually adverse tissue reactions (46.8%-169/361). Although this study has documented that unplanned interruptions are a major problem, the impact on local control and survival cannot be determined from our data. A retrospective review of multi-institutional studies such as those conducted by the Patterns of Care or RTOG might show that one of the major causes of failure is unplanned interruptions. PMID- 3350735 TI - More viewpoints on "veterinary technician". PMID- 3350734 TI - Preoperative planning of breast implants using the breast implant planning device (BIPD). AB - Interstitial implantation of the tumor excision site is an important component of the treatment program of breast-conserving surgery and irradiation. The currently accepted method of designing and performing the implant in the operating room does not assure adequate coverage of the volume of tissue at risk, i.e., the tissue immediately adjacent to the walls of the original tumor excision cavity. This communication describes a technique of preoperative implant planning that consistently and reliably ensures adequate coverage of the volume of tissue at risk. An integral part of this technique is the use of a new device called the Breast Implant Planning Device. This device is a modification of previously described implant template devices. PMID- 3350736 TI - Thoughts on merchandising. PMID- 3350738 TI - Client husbandry. PMID- 3350737 TI - Improving animal welfare. PMID- 3350739 TI - Air Force Environmental Health Services: the embodiment of veterinary public health. PMID- 3350740 TI - Efficacy of the morantel sustained-release bolus in grazing cattle in North America. AB - The efficacy of using a bolus containing morantel in a sustained-release preparation for controlling naturally acquired gastrointestinal parasitic infections in weaned calves and yearling cattle was investigated during the 1982 grazing season at selected sites in the United States and Canada. According to a common trial design under various climatic and management conditions, 10 field trials were conducted with the bolus. At the time of spring turnout, a bolus was administered to each calf or yearling in the treated group. Then, treated and control cattle grazed separate but equal areas of divided pasture(s). The epidemiologic pattern of parasitic gastroenteritis in control animals and the effect of treatment on this pattern was determined in each trial. Safety and practicality of use of the bolus also were established. When compared with untreated cattle (control), those given the bolus deposited significantly (P less than 0.05) fewer worm eggs (89% reduction) during the first 90 days of the grazing season, as well as significantly fewer (P less than 0.05) worm eggs (84% reduction) during the entire grazing season. Consequently, during the second half of the grazing season, larval populations on treated pastures remained significantly (P less than 0.05) lower (66% reduction), compared with numbers of larvae found on control pastures. For pastures grazed by treated and control cattle at trial initiation, mean worm counts recovered from tracer calves were equal, indicating comparable pasture contamination at the beginning of the grazing season.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350741 TI - Factors influencing litter size in swine: parity-one females. AB - The influence of age at conception, number of matings per conception, season of conception, and breed of female on parity-1 litter size was investigated in 4,944 females from 5 commercial swine herds located in North America. The influence of age at conception on reproductive performance of females in subsequent parities also was investigated. As the age at conception increased from 180 to 245 days, litter size increased 0.017 and 0.012 pig per day, respectively, (P less than 0.05) in 2 of the 3 herds that recorded such data. Age at conception did not influence litter size when conception occurred after 245 days of age. Longevity (parity achieved before death or culling) of females was not influenced by age at first conception. Gilts that conceived before 220 days of age had significantly shorter weaning-to-conception intervals in one herd and shorter farrowing-to conception intervals in another herd throughout subsequent parities. In 1 of 3 herds that recorded such data, live and total litter size increased from 9.46 to 10.46 and 10.16 to 11.50, respectively (P less than 0.05), as number of matings increased from 1 to 3 per conception. No significant influence of number of matings per conception was observed in the other 2 herds. The effect of season of conception was variable among herds. In 2 herds, there was no significant effect of season of conception on subsequent litter size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350743 TI - Acute mastitis and disseminated intravascular coagulopathy caused by Pasteurella haemolytica in a cow. AB - Pasteurella haemolytica was found to be the cause of acute mastitis, toxemia, and disseminated intravascular coagulopathy in a cow. Intensive treatment with antibiotics and fluid and heparin administration failed to reverse the progression of the disease, and death resulted. Necropsy revealed extensive evidence of consumptive coagulopathy, as well as mastitis. Pasteurella haemolytica rarely has been implicated as a cause of mastitis in cows. PMID- 3350744 TI - Uterine torsion of 720 degrees in a midgestation cow. AB - A 720 degrees uterine torsion was diagnosed in a cow at 161 days of gestation. The uterine torsion was reduced by laparotomy and intra-abdominal manipulation. An emphysematous fetus was removed vaginally. The cow was treated medically for associated metritis and peritonitis. Uterine torsions in cattle most commonly occur at parturition and only rarely exceed 360 degrees. PMID- 3350742 TI - Dorsal glottic stenosis after bilateral arytenoidectomy in two horses. AB - Bilateral arytenoidectomy had been performed as treatment for bilateral arytenoid chondritis in 2 horses. After surgery, dorsal mucosal defects were associated with subsequent development of dorsal glottic stenosis in the 2 horses. When performing bilateral arytenoidectomy in the horse, care must be taken to eliminate dorsal mucosal defects that cross the midline. Failure to close these defects may result in glottic stenosis. PMID- 3350745 TI - Jejunojejunal intussusception associated with a transmural adenocarcinoma in an aged cow. AB - After 3 days of intestinal obstruction, a proximal jejunojejunal intussusception was resected during surgery in an adult Holstein cow. A transmural adenocarcinoma was found at the proximal margin of the intussusception. The cow recovered well from surgery and produced milk and embryos to expectation. During the seventh month after surgery, the cow developed pneumonia and, therefore, was euthanatized. Disseminated abdominal and thoracic neoplasia was observed at necropsy. PMID- 3350746 TI - Acute hypocalcemia associated with infarction of parathyroid gland adenomas in two dogs. AB - Two dogs were examined because of anorexia, lethargy, muscle tremors, weakness, and seizures that were associated with an acute onset of hypocalcemia. Both dogs had histories of chronic hypercalcemia. Examination of the parathyroid glands revealed infarction of focal parathyroid adenomas, with atrophy of the remaining parathyroid glands. It was concluded that the acute onset of hypocalcemia was caused by infarction of functional parathyroid adenomas that were previously responsible for the cause of persistent hypercalcemia. Infarction of a parathyroid adenoma should be included in a list of differential diagnoses of acute hypocalcemia in the dog, especially if hypercalcemia has been diagnosed previously. PMID- 3350747 TI - Intracranial dermoid cyst in a dog. AB - A 7-year-old spayed bitch had a 3-year history of episodes of hind-limb weakness and ataxia. Neurologic abnormalities consisted of deficits in postural reactions, spinal reflexes, and conscious proprioception. A right-sided head tilt also was observed. Immediately after cervical radiography, CSF tap, and electroencephalography, the dog was alert, but it was found comatose the next morning and died within an hour. At necropsy, a 1.6- x 0.8- x 1.5-cm, thinly encapsulated mass was found on the left cerebellar peduncle. It had caused dorsal displacement of the left portion of the cerebellum and ventral compression of the fourth ventricle. Histologically, the mass was determined to be a dermoid cyst. PMID- 3350748 TI - Identification of Histoplasma organisms in circulating eosinophils of a dog. AB - Disseminated histoplasmosis was diagnosed in a 10-year-old dog that had chronic diarrhea, weight loss, fever, and anemia. The diagnosis was based on detection of Histoplasma organisms in circulating neutrophils, monocytes, and eosinophils. The dog had severe histoplasmal fungemia, which may have been caused by treatment with prednisolone. PMID- 3350749 TI - Primary pulmonary adenocarcinoma with brain stem metastasis in a dog. AB - Primary pulmonary adenocarcinoma with metastatic spread to the brain stem was diagnosed at necropsy in an aged Bulldog. Initial clinical signs included coughing, decreased exercise tolerance, and personality changes. Primary differential diagnoses after thoracic radiography were multicentric metastatic neoplasia or fungal disease. Later clinical signs (inappetence, unilateral facial paralysis and decreased sensation, and hemiparesis) were referable to the effect of the tumor on cranial nerves V and VII and other brain stem structures. Primary lung tumors are uncommon, as are metastatic tumors within the CNS. Radiographic appearance alone of lung lesions is insufficient for accurate diagnosis. PMID- 3350750 TI - Spontaneous regression of lymphosarcoma in a dog. AB - Lymphosarcoma in a dog regressed without chemotherapy or radiotherapy. The drugs administered to the dog before the regression were not sufficient to influence the neoplastic disease. During the next 12 months, the dog was evaluated periodically for signs of recurrence of the lymphosarcoma. The disease remained in clinical regression during this period. Spontaneous regression of lymphosarcoma in dogs is extraordinarily unusual. A variety of factors may affect remission in, and survival times of dogs with lymphosarcoma. PMID- 3350751 TI - Electrocardiographic abnormalities associated with tetanus in two dogs. AB - Bradycardia, sinus arrest, and second-degree atrioventricular block developed in 2 dogs with tetanus. Clinical signs attributable to bradycardia were not apparent. Administration of atropine resulted in resolution of the arrhythmias. Both dogs responded well to supportive treatment; the bradycardia resolved within 4 days of onset without specific treatment. Tetanus should be included in the differential diagnosis when increased neuromuscular excitability and bradycardia are evident, as is found in toxicity with acetylcholinesterase inhibitors, increased intracranial pressure, and other neurologic disorders. PMID- 3350753 TI - Animal health expenditures by livestock producers. PMID- 3350752 TI - Small intestinal adenocarcinoma in cats: 32 cases (1978-1985). AB - The medical records of 32 cats with small intestinal adenocarcinoma were reviewed. Common clinical signs included vomiting, dehydration, weight loss, cachexia, anorexia, and lethargy. In 50% of the cats, an abdominal mass was palpated, and in 38%, a mass was seen on radiographs. Biopsy of the tumor without resection was performed in 9 cats; 8 cats were euthanatized at the time of surgery, 7 because of metastases, and 1 cat died 1 day after surgery. In 23 cats, resection was performed. Eleven of these died within 2 weeks after surgery (mean survival time, 2.6 days); 8 had lymph node metastasis. Twelve cats survived greater than 2 weeks after surgery. The mean survival of 11 of these cats was 15 months. Six cats were euthanatized because of recurrent signs; 5 of the 6 had a recurrent abdominal mass. One cat was alive 2 years after surgery. Results of this study indicated that cats with adenocarcinoma, even those cats with advanced disease, can have long-term survival after surgery. PMID- 3350754 TI - Symposium on the Case for Responsible Extra-Label Drug Use. Presented at the 124th annual AVMA meeting. July 19-23, 1987, Chicago, Ill. Proceedings. PMID- 3350755 TI - Privileges and responsibilities relating to extra-label drug use. PMID- 3350756 TI - Use of human-label drugs in veterinary medicine. PMID- 3350757 TI - Specific information regarding withholding times associated with extra-label drug uses: selective condemnation. PMID- 3350758 TI - Quality assurance through residue screening. PMID- 3350759 TI - On the advisability and the feasibility of expanding the purposes and objectives of ASAHP: the report revisited. PMID- 3350760 TI - A view from Washington. PMID- 3350761 TI - Why, he's still alive! PMID- 3350762 TI - An interview with Senator Edward M. Kennedy. Interview by Janet I. Pisaneschi, Leopold G. Selker, Susan E. Siska, Arthur A. Savage and David C. Broski. PMID- 3350763 TI - ASAHP: coming of age. PMID- 3350764 TI - Twenty years of allied health. PMID- 3350765 TI - Out on a limb. PMID- 3350766 TI - The evolution of Jung's ideas on the transference. PMID- 3350767 TI - The well-springs of memory. PMID- 3350769 TI - Jung and homosexuality: a clearer vision. PMID- 3350768 TI - Archetypal foundations of projective identification. PMID- 3350770 TI - The sensitive period and optimum dosage for induction of audiogenic seizure susceptibility by kanamycin in the Wistar rat. AB - The incidence and severity of audiogenic seizures in kanamycin (KM)-treated rat pups, from a Wistar strain which is inherently seizure-resistant, was analyzed as a function of (a) postnatal age at the time of KM injection (i.p.) and (b) KM dosage. The vigor of the pinna reflex response on postnatal day (PND) 28 was correlated with (a) age at the time of injection, (b) dosage and (c) individual audiogenic seizure severity scores on PND 28 or PND 32. The data indicate that PNDs 9-12 are the developmental period when the rat has its greatest sensitivity to induction of susceptibility to audiogenic seizures by KM. The pinna reflex data suggest that cochlear vulnerability to KM intoxication is also greatest during this period. The optimum dosage for the induction of susceptibility was 100 mg/kg X 4 days. Use of higher doses resulted in a reduction of both incidence and severity of audiogenic seizures. The pinna reflex generally exhibited a supranormal vigor in animals having the most severe seizures. The behavioral attributes of induced audiogenic seizures at postnatal ages of 28 and 32 days are described and discussed. PMID- 3350771 TI - Effects of caffeine and tetracaine on outer hair cell shortening suggest intracellular calcium involvement. AB - Outer hair cell (OHC) shortening has previously been induced in vitro by the application of solutions containing high potassium (a depolarizing agent), acetylcholine (a suggested efferent transmitter) and cationized ferritin (a positively charged macromolecule), as well as by electrical current. The application of caffeine, which causes contractures in skeletal and smooth muscle by releasing calcium from intracellular stores to activate actin and myosin interaction, also causes shortening of OHCs. Tetracaine, which interferes with calcium movement in muscle and non-muscle cells, blocks potassium-induced and caffeine-induced shortening of OHCs, but does not block electrically-induced shortening. Sodium dantrolene which is an inhibitor of intracellular calcium release in skeletal muscle does not block potassium-induced OHC shortening. Immunocytochemical studies using antibodies to muscle-like contractile and regulatory proteins on unfixed, freeze-dried OHCs demonstrate the co-localization of calmodulin with actin throughout the OHC cytoplasm. These results support the ideas that in OHCs, intracellular calcium release is involved in the activation of shortening and that an actin-mediated cell shape change may be regulated by calmodulin in a manner similar to that which occurs in contraction of smooth muscle. PMID- 3350772 TI - Failure of a missing-fundamental complex to interact with masked and unmasked pure tones at its fundamental frequency. AB - Of interest here are the mechanisms underlying the extraction of temporal periodicities from complex acoustic stimuli. Two extreme versions of the underlying mechanisms are examined for possible psychophysical consequences, and experiments of two sorts are reported. In one, the detectability of a 200-Hz tone was measured in the presence, and the absence, of a tonal complex that gives rise to the experience of a missing fundamental having a pitch of 200 Hz in an attempt to see if the missing-fundamental waveform contributes to the masking of the tonal signal. We call this periodicity masking, but were unable to measure any, implying that if periodicity information was being used both to detect the signal and to perceive the missing fundamental, those two streams of afferent information are kept separate by the auditory nervous system, at least initially. In the second set of experiments, an "informational-masking" paradigm was used to introduce high uncertainty about the frequency of the tonal signal, and both detection and frequency discrimination were measured in the presence and absence of a missing-fundamental complex. This time the question was whether the periodicity information in the complex would produce a reduction in the frequency uncertainty about the signal and, thereby, improve performance. We call this possible effect periodicity cueing, but were unable to find evidence for its existence either. The failure to find either periodicity masking or periodicity cueing is discussed in regard to possible organizations of the auditory system, and in regard to the "periodicity-rate gap" seen in primary auditory fibers. PMID- 3350773 TI - Atrophy of middle and short stereocilia on outer hair cells of guinea pig cochleas with experimentally induced hydrops. AB - Scanning electron microscopy was employed to investigate hair cell morphology at different stages in the development of experimentally induced hydrops in the guinea pig. A particular form of morpho-pathology, never before described, was identified as characteristic of hydropic cochleas. The pathology was characteristically identified as atrophy of the short and middle stereocilia on the outer hair cells while the inner hair cell stereocilia did not have such a pathology. The atrophy was restricted to the upper cochlear turns in remarkable correspondence with the low/middle frequency sensitivity loss and was detected only at the end of the period of fluctuating thresholds. These stereocilia perturbations appear therefore to be linked with the threshold fluctuations and represent the first evidence for a clear correlation between hair cell morphology and physiology in the experimental model of endolymphatic hydrops. Such a morphopathology might also be expected to occur in cochleas of Meniere's patients but may have been overlooked in the past because of the discrete nature of the pathology. PMID- 3350774 TI - Representation of amplitude modulation in the auditory cortex of the cat. II. Comparison between cortical fields. AB - The responses of neuronal clusters to amplitude-modulated tones were studied in five auditory cortical fields of the anesthetized cat: the primary auditory field (AI), second auditory field (AII), anterior auditory field (AAF), posterior auditory field (PAF) and the ventro-posterior auditory field (VPAF). Modulation transfer functions (MTFs) for amplitude-modulated tones were obtained at 172 cortical locations. MTFs were constructed by measuring firing rate (rate-MTFs) and response synchronization (synchronization-MTFs) to sinusoidal and rectangular waveform modulation of CF-tones. The MTFs were characterized by their 'best modulation frequency' (BMF) and a measure of their quality of 'sharpness' (Q2dB). These characteristics were compared for the five fields. Rate and synchronization MTFs for sinusoidal and rectangular modulation produced similar estimates of BMF and Q2dB. Comparison of averaged BMFs between the cortical fields revealed relatively high BMFs in AAF (mean: 31.1 Hz for synchronization to sinusoidal AM) and moderately high BMFs in AI (14.2 Hz) whereas BMFs encountered in AII, VPAF and PAF were generally low (7.0, 5.2, and 6.8 Hz). The MTFs were relatively broadly tuned (low Q2dB) in AAF and sharper in a low modulation group containing AII, PAF and VPAF. The ventro-posterior field was the most sensitive to changes in the modulation waveform. We conclude that there are significant differences between auditory cortical fields with respect to their temporal response characteristics and that the assessment of these response characteristics reveals important aspects of the functional significance of auditory cortical fields for the coding and representation of complex sounds. PMID- 3350775 TI - The development and decline of forward masking. AB - Three experiments investigated the forward masking of brief sinusoids by bursts of noise for masker durations of between 5 and 320 ms and for masker-signal delays between 5 and 40 ms. Experiment 1 showed that, for a 2-kHz signal and a 5 ms delay, long-duration maskers produced much more masking than brief maskers of the same spectrum level. As masker-signal delay was increased, thresholds dropped more rapidly for long than for brief maskers, so that at a delay of 40 ms the difference between thresholds produced by long and by brief maskers was reduced. Experiment 2 showed that, for a 2-kHz signal, the transition from simultaneous masking to forward masking was accompanied by a large drop of about 23 dB in threshold. For a 250-Hz signal this large drop did not occur until masker-signal delay was increased from 10 to 20 ms. For shorter masker-signal delays, brief 250 Hz maskers produced thresholds higher than those produced by longer maskers. The results of Experiment 2 are consistent with the idea that ringing on the basilar membrane causes the responses to masker and signal to overlap for delay times up to 10 ms. Experiment 3 compared the recovery functions for 3 markers of different durations, where the masker levels were adjusted so that each produced equal masking of a 2-kHz signal at a delay of 5 ms. Brief intense maskers produced slower recovery than longer weaker ones, indicating that the recovery from a given amount of forward masking depends on how that masking developed. The implications of this finding for attempts to explain forward masking in terms of short-term adaptation are discussed. PMID- 3350776 TI - The phase response of primary auditory afferents in a songbird (Sturnus vulgaris L.). AB - The effects of stimulus frequency and intensity on phase-locking characteristics of cochlear ganglion cells were studied in the starling. All cells showed phase locking to tone stimuli within their response area. Phase-locking at CF is found on average 9 dB below discharge rate threshold. Phase-locking is best at 0.4 kHz and deteriorates with increasing frequency almost independently of CF. No phase locking was evident for test frequencies above 3-4 kHz. Phase-locking in cells with CFs above 1.0 kHz is better below CF than at CF. For constant sound pressure, an increase in stimulus frequency always produced an increase in phase lag of the neural response. The phase vs. frequency data obtained at constant sound pressure can be reasonably approximated by straight line functions. The slopes of these functions indicate the latency of the neural response, and are correlated with the CFs of the respective cells; the latency tends to be longer in low-CF cells and shorter in high-CF cells. The latency decreases by 0.04 ms per 1 dB sound pressure increase. The response phase at CF is nearly stimulus level-independent. Increasing stimulus intensity causes increasing phase lag below CF and decreasing phase lag above CF. These results are compared to findings in other vertebrates and demonstrate the similarities of phase-locking characteristics despite the substantial anatomical differences among the vertebrate groups. PMID- 3350778 TI - Sexism in gynecology textbooks: gender stereotypes and paternalism, 1978 through 1983. PMID- 3350777 TI - Developmental changes in frequency mapping of the gerbil cochlea: comparison of two cochlear locations. AB - The cochlear microphonic measured in scala tympani referenced to that at the round window is used to determine characteristic frequency (CF) at two locations in an age-graded series of Mongolian gerbils. No significant ontogenic shift in CF is seen at a second turn location, while an approximately 1.5 octave shift is seen in the mid-basal turn. PMID- 3350779 TI - A survey of physicians' attitudes and behavior toward PMS. PMID- 3350781 TI - Rurality, stress, and illness among women: a pilot study. PMID- 3350780 TI - Self-care practices among young adult women: influence of symptoms, employment, and sex-role orientation. PMID- 3350782 TI - Experimental aflatoxin production in Manchego-type cheese. AB - Manchego-type cheese, a typical Spanish cheese, was inoculated in various ways with an aflatoxigenic organism, Aspergillus parasiticus NRRL 2999, to study the production of aflatoxin. When the original milk was contaminated with a spore suspension, aflatoxin was not detected in paraffin-covered cheeses although it was present in the top layer of non-paraffin-covered cheeses after ripening at 15 degrees C for 60 d. When the cheese surface was inoculated, no aflatoxins were detected in paraffin-covered cheeses after ripening for 60 d although they were found when the cheeses were ripened for 30 d. In non-paraffin-covered cheeses aflatoxins were detected only in the top layer and in the second 10 mm layer when cheeses were incubated after the normal ripening at 28 degrees C for 30 d. When the centre of the cheese was inoculated, no aflatoxins were detected although Aspergillus grew slightly along the inoculation area. When cheese portions were inoculated, fungal growth was evident after incubation at 28 degrees and 15 degrees C for 6 d but there was no growth at 10 degrees C after 50 d. At 28 degrees C aflatoxins were detected at a concentration of 132 micrograms/g after 13 d, the highest level obtained. In cheese paste at 28 degrees and 15 degrees C, growth was intense, but the level of aflatoxins detected was lower than in cheese portions. At 10 degrees C the growth was heavy, but aflatoxins were not detected. PMID- 3350783 TI - Numerical analysis of electrophoretic protein patterns of Providencia alcalifaciens strains from human faeces and veterinary specimens. AB - Twenty-five strains of Providencia alcalifaciens from various countries have been characterized by one-dimensional SDS-PAGE of cellular proteins. They comprised 15 from human faeces, one from duck faeces, one from a guinea-pig eye and eight from unknown sources. Also included, for reference purposes, were the type strains of three other Providencia species. The protein patterns, which contained 45-50 discrete bands, were highly reproducible and were used as the basis for two numerical analyses. In the first, in which the principal protein bands (in the 33 40 kD range) were excluded, the 25 Prov. alcalifaciens strains formed, at the 83% S level, a single cluster whilst the three Providencia reference strains remained unclustered. In the second, which included all the protein bands, the 25 Prov. alcalifaciens strains formed 10 clusters at the 85% S level. We conclude that high resolution PAGE combined with computerized analysis of protein patterns provides the basis for typing clinical strains of Prov. alcalifaciens. Reference strains of each of the 10 PAGE types identified are available from NCTC for inclusion in future studies. PMID- 3350784 TI - Relation of job stressors to affective, health, and performance outcomes: a comparison of multiple data sources. PMID- 3350785 TI - Maintenance of highly contractile tissue-cultured avian skeletal myotubes in collagen gel. AB - Highly contractile skeletal myotubes differentiated in tissue culture are normally difficult to maintain on collagen-coated tissue culture dishes for extended periods because of their propensity to detach as a sheet of cells from their substratum. This detachment results in the release of mechanical tension in the growing cell "sheet" and, consequently, loss of cellular protein. We developed a simple method of culturing high density contractile primary avian myotubes embedded in a collagen gel matrix (collagel) attached to either a stainless steel mesh or nylon support structure. With this system the cells are maintained in a highly contractile state for extended periods in vitro under tension. Structural integrity of the myotubes can be maintained for up to 10 d in basal medium without serum or embryo extract. Total cellular protein and myosin heavy chain accumulation in the cells can be maintained for weeks at levels which are two to three times those found in time-matched controls that are under little tension. Morphologically, the myotubes are well differentiated with structural characteristics of neonatal myofibers. This new collagel culture system should prove useful in the analysis of in vitro gene expression during myotube to myofiber differentiation and its regulation by various environmental factors such as medium growth factors, innervation, and mechanical activity. PMID- 3350786 TI - A macrophage-monocyte cell line from a dog with malignant histiocytosis. AB - The DH82 cell line was established from the neoplastic progenitor cells of canine MH and was characterized as histiocytic in origin based on light microscopic and ultrastructural morphology, positive staining reactions for alpha naphthyl acetate esterase and acid phosphatase, presence of Fc receptors, phagocytosis of latex beads, and plastic adherence in culture. PMID- 3350787 TI - The methanoreductosome: a high-molecular-weight enzyme complex in the methanogenic bacterium strain Go1 that contains components of the methylreductase system. AB - The methanogenic bacterium strain Go1 harbors a high-molecular-weight enzyme complex containing methyl coenzyme M methylreductase as revealed by immunoelectron microscopy. This complex consists of a spherelike, hollow head piece, in the wall of which a number of copies of the methyl coenzyme M methylreductase are located. It is named Rc (c indicates collector). Intimately bound to it is a group of additional subunits of unknown composition referred to as Rm (m indicates mediator). Electron microscopy of negatively stained samples indicated that Rm contains a functional pore or channel which connects the internal volume of Rc with the outside. The RcRm complex is named Rs (s indicates spherelike). This complex was often found detached from the inside of the cytoplasmic membrane when membrane vesicles were investigated. However, Rs was also seen attached to a third component of the complex located in the membrane, the attachment being mediated by Rm. This membrane part of the complex is designated Rt (t indicates translocator). It consists of subunits with unknown composition. When Rs is attached to the membrane, the pore in Rm appears to be plugged by Rt. This indicates that the internal volume in Rc is in contact, via the pore in Rm, with Rt. The RcRmRt complex is referred to as methanoreductosome. Functional implications of the structural organization of the methylreductase system are discussed in view of methane formation and the creation of a transmembrane proton gradient used by the cell for ATP synthesis. PMID- 3350788 TI - Purification and properties of benzoate-coenzyme A ligase, a Rhodopseudomonas palustris enzyme involved in the anaerobic degradation of benzoate. AB - A soluble benzoate-coenzyme A (CoA) ligase was purified from the phototrophic bacterium Rhodopseudomonas palustris. Synthesis of the enzyme was induced when cells were grown anaerobically in light with benzoate as the sole carbon source. Purification by chromatography successively on hydroxylapatite, phenyl-Sepharose, and hydroxylapatite yielded an electrophoretically homogeneous enzyme preparation with a specific activity of 25 mumol/min per mg of protein and a molecular weight of 60,000. The purified enzyme was insensitive to oxygen and catalyzed the Mg2+ ATP-dependent formation of acyl-CoA from carboxylate and free reduced CoA, with high specificity for benzoate and 2-fluorobenzoate. Apparent Km values of 0.6 to 2 microM for benzoate, 2 to 3 microM for ATP, and 90 to 120 microM for reduced CoA were determined. The reaction product, benzoyl-CoA, was an effective inhibitor of the ligase reaction. The kinetic properties of the enzyme match the kinetics of substrate uptake by whole cells and confirm a role for benzoate-CoA ligase in maintaining entry of benzoate into cells as well as in catalyzing the first step in the anaerobic degradation of benzoate by R. palustris. PMID- 3350789 TI - Evidence for two different gas vesicle proteins and genes in Halobacterium halobium. AB - Most halobacteria produce gas vesicles (GV). The well-characterized species Halobacterium halobium and some GV+ revertants of GV- mutants of H. halobium produce large amounts of GV which have a spindlelike shape. Most other GV+ revertants of H. halobium GV- mutants and other recently characterized halobacterial wild-type strains possess GV with a cylindrical form. The number of intact particles in the latter isolates is only 10 to 30% of that of H. halobium. Analysis of GV envelope proteins (GVPs) by electrophoresis on phenol-acetic acid urea gels showed that the GVP of the highly efficient GV-producing strains migrated faster than the GVP of the low-GV-producing strains. The relative molecular mass of the GVP was estimated to be 19 kilodaltons (kDa) for high producing strains (GVP-A) and 20 kDa for low-producing strains (GVP-B). Amino acid sequence analysis of the first 40 amino acids of the N-terminal parts of GVP A and GVP-B indicated that the two proteins differed in two defined positions. GVP-B, in relation to GVP-A, had Gly-7 and Val-28 always replaced by Ser-7 and Ile-28, respectively. These data suggest that at least two different gvp genes exist in H. halobium NRL. This was directly demonstrated by hybridization experiments with gvp-specific DNA probes. A fragment of plasmid pHH1 and a chromosomal fragment of H. halobium hybridized to the probes. Only a chromosomal fragment hybridized to the same gyp probes when both chromosomal and plasmid DNAs from the low-GV-producing halobacterial wild-type strains SB3 and GN101 were examined. These findings support the assumption that GVP-A is expressed by a pHH1 associated gvp gene and GVP-B by a chromosomal gvp gene. PMID- 3350791 TI - Purification and characterization of a bacterial nitrophenol oxygenase which converts ortho-nitrophenol to catechol and nitrite. AB - A nitrophenol oxygenase which stoichiometrically converted ortho-nitrophenol (ONP) to catechol and nitrite was isolated from Pseudomonas putida B2 and purified. The substrate specificity of the enzyme was broad and included several halogen- and alkyl-substituted ONPs. The oxygenase consisted of a single polypeptide chain with a molecular weight of 58,000 (determined by gel filtration) or 65,000 (determined on a sodium dodecyl sulfate-polyacrylamide gel). The enzymatic reaction was NADPH dependent, and one molecule of oxygen was consumed per molecule of ONP converted. Enzymatic activity was stimulated by magnesium or manganese ions, whereas the addition of flavin adenine dinucleotide, flavin mononucleotide, or reducing agents had no effect. The apparent Kms for ONP and NADPH were 8 and 140 microM, respectively. 2,4-Dinitrophenol competitively (Ki = 0.5 microM) inhibited ONP turnover. The optimal pH for enzyme stability and activity was in the range of 7.5 to 8.0. At 40 degrees C, the enzyme was totally inactivated within 2 min; however, in the presence of 1 mM ONP, 40% of the activity was recovered, even after 10 min. Enzymatic activity was best preserved at -20 degrees C in the presence of 50% glycerol. PMID- 3350790 TI - Motility and chemotaxis of Spirochaeta aurantia: computer-assisted motion analysis. AB - A computer program has been designed to study behavior in populations of Spirochaeta aurantia cells, and this program has been used to analyze changes in behavior in response to chemoattractants. Three kinds of behavior were distinguished: smooth swimming, flexing, and reversals in direction of swimming after a short pause (120 ms). Cell populations exposed to chemoattractants spent, on average, 66, 33, and 1% of the time in these modes, respectively. After the addition of a chemoattractant, behavior was modified transiently--smooth swimming increased, flexing decreased, and reversals were suppressed. After addition of D xylose (final concentration, 10 mM), the adaptation time (the time required for the populations to return to the unmodified behavior) for S. aurantia was 1.5 to 2.0 min. A model to explain the behavior of S. aurantia and the response of cells to chemoattractants is described. This model includes a coordinating mechanism for flagellar motor operation and a motor switch synchronizing device. PMID- 3350792 TI - Purification and characterization of an arginine-specific carboxypeptidase from Mycoplasma salivarium. AB - The carboxypeptidase which had been shown to be present exclusively in nonfermentative mycoplasmas was found to be associated with cell membranes of Mycoplasma salivarium. The enzyme was released from the membranes with Triton X 100 and purified by ion-exchange chromatography on DEAE-Sephacel, affinity chromatography on arginine-Sepharose 4B, and chromatofocusing. The purified enzyme had a molecular mass of 218 kilodaltons, as estimated by gel filtration through Sepharose CL-6B, and yielded one band of activity in analytical disc polyacrylamide gel electrophoresis performed in the presence of 0.5% (wt/vol) Triton X-100. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme treated in the presence or absence of 2-mercaptoethanol revealed one band with a molecular mass of 87 kilodaltons. The enzyme catalyzed selectively the cleavage of the C-terminal arginine residue of peptides such as N benzoylglycyl-L-arginine, tuftsin, and bradykinin and was inhibited considerably by o-phenanthroline and EDTA but only slightly by NiCl2. The inhibition of the enzyme by EDTA was fully reversed by the addition of ZnCl2, whereas the addition of CoCl2 activated the enzyme. PMID- 3350794 TI - Lack of carbon substrate repression of uptake hydrogenase activity in Bradyrhizobium japonicum SR. AB - The expression of ex planta uptake hydrogenase (Hup) activity in Bradyrhizobium japonicum SR induced in the absence or presence of carbon substrates was compared. Hup activity was influenced by pH, indicating that acidification of induction medium with low buffering capacity resulting from carbon substrate metabolism inhibited Hup activity. Cell suspensions in medium with adequate buffering capacity and carbon substrate were limited in O2; increasing O2 availability to cells during induction stimulated Hup expression. The data showed a lack of carbon substrate repression of Hup activity in cell suspensions provided with adequate O2 and buffering capacity. PMID- 3350795 TI - Plasmids of Azotobacter vinelandii. AB - Four laboratory strains and two isolates of Azotobacter vinelandii were found to contain plasmids. Twenty-five laboratory strains which could fix nitrogen did not have free, covalently closed circular plasmid DNA. The plasmids varied in size from 9 to 52 megadaltons, and each strain yielded only one plasmid. No discernible differences in ability to fix nitrogen were found between plasmid bearing and cured cultures. PMID- 3350793 TI - Purification and properties of glutamate synthase from Nocardia mediterranei. AB - Glutamate synthase was purified about 250-fold from Nocardia mediterranei U32 and characterized. The native enzyme has a molecular weight of 195,000 +/- 5,000 and is composed of two nonidentical subunits with molecular weights of 145,000 +/- 5,000 and 55,000 +/- 3,000. This enzyme is a complex of iron-sulfur flavoproteins with absorption maxima at 278, 375, 410, and 440 nm. It contains 1.1 mol of flavin adenine dinucleotide, 1.0 mol of flavin mononucleotide, 7.5 mol of nonheme iron, and 7.2 mol of acid-labile sulfur per 200,000 g of protein. Km values for L glutamine, alpha-ketoglutarate, and NADPH were 77, 53, and 110 microM, respectively. The activity of this glutamate synthase is inhibited by its products (i.e., glutamate and NADP), several amino acids, and tricarboxylic acid cycle intermediates. PMID- 3350796 TI - Hydrogen-mediated mannose uptake in Azotobacter vinelandii. AB - Azotobacter vinelandii can grow mixotrophically with H2 plus mannose under N2 fixing conditions (T. Y. Wong and R. J. Maier, J. Bacteriol. 163:528-533, 1985). Mixotrophically grown cultures incubated in H2 transported mannose with a Vmax fourfold greater than that observed for cultures incubated in argon, but H2 did not change the apparent Km for mannose. Respiratory inhibitors, such as potassium cyanide, hydroxylamine, and p-chloromercuribenzoic acid, as well as the proton conductor carbonyl cyanide m-chlorophenyl-hydrazone inhibited mannose uptake. We suggest that one of the roles of H2 in mixotrophic metabolism is to supply energy that facilitates mannose transport. PMID- 3350797 TI - Identification of a new Bradyrhizobium japonicum gene (frxA) encoding a ferredoxinlike protein. AB - An open reading frame of 74 codons was identified downstream of the nifB gene of Bradyrhizobium japonicum 110. The predicted amino acid sequence shared 63% similarity with the Rhodopseudomonas palustris ferredoxin I sequence. We propose to name the gene frxA. The frxA gene was found to be cotranscribed with the nifB gene. An insertion mutation within frxA hardly affected nitrogen fixation activity. PMID- 3350798 TI - Carbamazepine use in neuropsychiatry. Seattle, Washington, October 30, 1987. Proceedings. PMID- 3350799 TI - A 15-kDa interferon-induced protein is derived by COOH-terminal processing of a 17-kDa precursor. AB - An interferon-induced 15-kDa protein is synthesized from a precursor of higher molecular weight; the precursor contains 165 amino acids (17 kDa), whereas the stable product (15 kDa) contains 156 amino acids. The stable 15-kDa form is derived from the precursor 17-kDa form by the removal of eight amino acids from the COOH terminus and the methionine from the NH2 terminus. The existence of the precursor 17-kDa protein can be demonstrated after brief periods of in vivo labeling with [35S]methionine and by translation of mRNA in vitro. PMID- 3350800 TI - S-adenosyl-L-methionine:thioether S-methyltransferase, a new enzyme in sulfur and selenium metabolism. AB - The final urinary excretion product of selenium detoxification is trimethylselenonium ion. An assay has been developed for the enzyme, S adenosylmethionine:thioether S-methyltransferase, responsible for this final methylation reaction. This assay employed high pressure liquid chromatography separation and quantitation of the trimethylselenonium ion produced by thioether methyltransferase acting on S-adenosylmethionine and dimethyl selenide. The enzyme was shown to reside primarily in the cytosol of mouse lung (30 pmol/mg protein/min) and liver (7 pmol/mg protein/min). Purification from mouse lung to a preparation that exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was achieved by DEAE, gel filtration, and chromatofocusing chromatographies. Thioether methyltransferase is monomeric with a molecular weight of 28,000 and has a pI of 5.3. The pH optimum was 6.3, and Km values for dimethyl selenide and S-adenosylmethionine were 0.4 and 1.0 microM, respectively. The enzyme was inhibited 50% by 25 microM sinefungin, an analog of S adenosylmethionine, or 40 microM S-adenosylhomocysteine, the reaction product. Pure thioether methyltransferase methylated selenium in dimethyl selenide, tellurium in dimethyl telluride, and S in dimethyl sulfide and many other thioethers. These data suggest a general role for this novel enzyme in the synthesis of onium compounds with increased aqueous solubility helpful in their excretion. PMID- 3350801 TI - The effect of filament shortening on the mechanical properties of gel-filtered actin. AB - To address the claim that filaments polymerized from highly purified (gel filtered) F-actin acquire the elastic properties of a solid attributable to chemical cross-linking, we measured the rheologic spectrum of the dynamic storage modulus, G', and loss modulus, G'' from 5 x 10(-4) to 0.5 Hz for gel-filtered actin alone and in the presence of the actin shortening protein, gelsolin. We confirmed that gel-filtered filamentous actin is a highly elastic material as evidenced by a relatively frequency-independent G', which is consistent with either topologically constrained filaments or a chemically cross-linked gel. Introduction of gel-filtered actin oligomers, however, caused the behavior of gel filtered actin to become more frequency-dependent and almost identical to that of non-gel-filtered actin, suggesting that the effect of gel filtration on the mechanical behavior of actin is topologic. This conclusion is further supported by the finding that shortening of the actin filaments by the addition of gelsolin at molar ratios to actin of from 1:8000 to 1:500 causes a gradual decrease in elasticity and increase in the amount of flow. PMID- 3350802 TI - Activation of protein kinase C by short chain phosphatidylcholines. AB - The acidic phospholipid requirement for protein kinase C (Ca2+/phospholipid dependent enzyme) activation has been well established, although the molecular nature of this lipid-protein interaction is unclear. The additional requirement for Ca2+ has provided the basis for several models involving charge interactions. We now report that short chain neutral phosphatidylcholines also activate the kinase. Examination of a large series of phosphatidylcholines of varying acyl chain length revealed a close correlation between the ability to form micelles and the ability to support kinase activity. Peak activation occurred in the concentration range just before the critical micelle concentration of each phospholipid. Activation was absolutely dependent on the presence of Ca2+ and diacylglycerol. The possible roles of Ca2+ and phospholipid in the activation process are reexamined in light of these unexpected results. PMID- 3350803 TI - Intracellular transport of class I histocompatibility molecules. Influence of protein folding on transport to the cell surface. AB - To examine the structural requirements for the intracellular transport and surface expression of Class I histocompatibility molecules, we studied somatic cell variants that produce altered forms of the H-2Kb molecule. One variant, R8.10, produced a mutant Kb molecule that was expressed on the cell surface at about 15% of the wild-type level. Nucleic acid sequence analysis identified the mutation as a single nucleotide change resulting in an amino acid substitution (Trp----Arg) at residue 167 in the alpha 2 extracellular domain. A comparative kinetic analysis of the intracellular transport of the wild-type and mutant molecules revealed that transport of the mutant product was remarkably impaired. Whereas wild-type molecules arrived at the cell surface with a half-time of about 30 min, 80% of newly synthesized mutant molecules did not progress beyond the rough endoplasmic reticulum, where they were slowly degraded. Surprisingly, the remaining 20% of the mutant population was capable of reaching the plasma membrane at a rate about one-half that of wild-type Kb. The accumulation of most of the mutant molecules in the rough endoplasmic reticulum was not due to aggregation or insolubility, nor could it be attributed to a lack of association with beta 2-microglobulin. Several techniques were employed in an effort to detect structural features unique to the transport-deficient mutant population. Monoclonal antibody binding experiments revealed structural differences between wild-type and mutant molecules in the region of the mutation but failed to distinguish the transport-competent and -deficient mutant populations. Detergent partitioning studies were also ineffective in this regard. However, differences between transported and untransported molecules were readily demonstrated by their disparate susceptibilities to proteolytic digestion. The results indicated that the transport-deficient form of the mutant assumed a conformation that was altered relative to both the transport-competent form and the wild-type molecule. The fact that the ability of wild-type and mutant molecules to be transported correlated with conformational features rather than with their specific primary sequences suggests that proper folding is an important requirement for their passage through the exocytotic pathway. PMID- 3350804 TI - Evidence for an organic cation-proton antiport system in brush-border membranes isolated from the human term placenta. AB - Uptake of guanidine, an endogenous organic cation, into brush-border membrane vesicles isolated from human term placentas was investigated. Initial uptake rates were manyfold greater in the presence of an outward-directed H+ gradient ([pH]o greater than [pH]i) than in the absence of a H+ gradient ([pH]o = [pH]i). Guanidine was transiently accumulated inside the vesicles against a concentration gradient in the presence of the H+ gradient. The H+ gradient-dependent stimulation of guanidine uptake was not due to a H+-diffusion potential because an ionophore (valinomycin or carbonylcyanide p-trifluoromethoxyphenylhydrazone) induced inside-negative membrane potential failed to stimulate the uptake. In addition, uphill transport of guanidine could be demonstrated even in voltage clamped membrane vesicles. The H+ gradient-dependent uptake of guanidine was inhibited by many exogenous as well as endogenous organic cations (cis inhibition) but not by cationic amino acids. The presence of unlabeled guanidine inside the vesicles stimulated the uptake of labeled guanidine (trans stimulation). These data provide evidence for the presence of an organic cation proton antiporter in human placental brush-border membranes. Kinetic analysis of guanidine uptake demonstrated that the uptake occurred via two saturable, carrier mediated transport systems, one being a high affinity, low capacity type and the other a low affinity, high capacity type. Studies on the effects of various cations on the organic cation-proton antiporter and the Na+-H+ exchanger revealed that these two transport systems are distinct. PMID- 3350805 TI - Novel kinetics of single cell Ca2+ transients in stimulated hepatocytes and A10 cells measured using fura-2 and fluorescent videomicroscopy. AB - The kinetics of agonist-induced increases in cytosolic free Ca2+ have been measured in single A10 vascular smooth muscle cells and rat hepatocytes using fluorescent videomicroscopy with fura-2 as a Ca2+ indicator. At high agonist concentrations there was no difference in the kinetics of the Ca2+ transient measured in vasopressin-stimulated single A10 cells or in cell populations. However, stimulation of single A10 cells with concentrations of vasopressin below 0.5 nM produced characteristic Ca2+ transients composed of two distinct peaks. The two peaks appeared to represent a temporal separation between release of intracellular Ca2+ and influx of extracellular Ca2+. The double transient was not observed in single rat hepatocytes stimulated with low concentrations of vasopressin or phenylephrine. In both A10 cells and hepatocytes, the initial rate of increase in Ca2+ concentrations in response to submaximal agonist concentrations was faster in single cells than in cell populations. This difference was due to asynchrony of the cellular response, where there was a latent period of variable length before onset of a rapid increase in Ca2+ concentration. The duration of the latent period was dependent on the agonist concentration, higher concentrations of agonist giving a reduced latent period. The hormone-stimulated Ca2+ transient measured in single hepatocytes with fura-2 was different from the series of transient spikes as previously reported using aequorin as the Ca2+ indicator, suggesting that fura-2 and aequorin may report different aspects of the Ca2+ response in stimulated cells. Collectively, these results demonstrate that measurement of Ca2+ transients in single cells provide novel information concerning the nature of the Ca2+ transient that is not apparent from studies with cell populations. PMID- 3350806 TI - The immobilized leukoagglutinin from the seeds of Maackia amurensis binds with high affinity to complex-type Asn-linked oligosaccharides containing terminal sialic acid-linked alpha-2,3 to penultimate galactose residues. AB - We recently reported that the purified leukoagglutinin (designated MAL) from the seeds of the leguminous plant Maackia amurensis is a potent leukoagglutinin for the mouse lymphoma cell line BW5147 (Wang, W.-C., and Cummings, R. D. (1987) Anal. Biochem. 161,80). We and others have shown that this lectin is a weak hemagglutinin of human erythrocytes (Kawaguchi, T., Matsumoto, I., and Osawa, T. (1974) J. Biol. Chem. 249, 2786). We now report that leukoagglutination by MAL is inhibited by low concentrations of 2,3-sialyllactose (NeuAc alpha 2,3Gal beta 1,4Glc), but it is not inhibited by either 2,6-sialyllactose (NeuAc alpha 2,6Gal beta-1,4Glc), lactose, or free NeuAc. To further study the carbohydrate-binding specificity of this lectin, we investigated the interactions of immobilized MAL with glycopeptides prepared from the mouse lymphoma cell line BW5147 and from purified glycoproteins. We found that immobilized MAL interacts with high affinity with complex-type tri- and tetraantennary Asn-linked oligosaccharides containing outer sialic acid residues linked alpha 2,3 to penultimate galactose residues. Glycopeptides containing sialic acid linked only alpha 2,6 to penultimate galactose did not interact detectably with the immobilized lectin. Our analyses indicate that the interactions of complex-type Asn-linked chains with the lectin are dependent on sialic acid linkages and are not dependent on either the branching pattern of the mannose residues or the presence of poly-N acetyllactosamine sequences. PMID- 3350808 TI - The kinetic mechanism of the release of nucleotide from elongation factor Tu promoted by elongation factor Ts determined by pressure relaxation studies. AB - The release of a chromophoric analogue of GDP, 2-amino-6-mercaptopurine riboside 5'-diphosphate (thioGDP), from its complex with elongation factor Tu (EF-Tu) is catalyzed by elongation factor Ts (EF-Ts). The mechanism of this reaction includes a ternary complex; EF-Tu.thioGDP.EF-Ts (Eccleston, J. F. (1984) J. Biol. Chem. 259, 12997-13003). This mechanism has been further investigated using pressure relaxation techniques combined with spectrophotometric measurements. The equilibrium of a solution of EF-Tu, EF-Ts, and thioGDP over a range of concentrations is perturbed on increasing the pressure to 150 atm. Rapid decrease of the pressure back to 1 atm results in a biphasic relaxation process, an initial fast phase which is complete within 1 ms followed by a slower phase. This is interpreted as the result of an isomerization of the EF-Tu.thioGDP.EF-Ts ternary complex which occurs before the release of thioGDP. Such an isomerization process may be a general feature in the release of GDP from guanosine nucleotide binding proteins. PMID- 3350807 TI - Inhibition of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid oxidation and of bile acid secretion in rat liver by fatty acids. AB - In isolated rat hepatocytes, fatty acids inhibited the side chain oxidation, but not the uptake, of exogenously added 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta cholestan-26-oic acid (THCA). THCA did not inhibit fatty acid oxidation. In liver homogenates, fatty acids inhibited THCA activation to its CoA ester (THC-CoA) and THCA oxidation. THCA did not influence fatty acid activation or oxidation. Comparison of the THC-CoA concentrations present in the incubation mixtures during THCA oxidation, with substrate concentration curves determined for THC-CoA oxidation, indicated that the inhibition of THCA oxidation by fatty acids was at least partly exerted at the activation step. The inhibition of THCA activation by fatty acids was noncompetitive. Palmitoyl-CoA at concentrations found in the incubation mixtures during THCA oxidation in the presence of palmitate inhibited THC-CoA oxidation, but not sufficiently to fully explain the fatty acid-induced inhibition of THCA oxidation. The inhibition of THC-CoA oxidation by palmitoyl CoA did not seem to be competitive. Acyl-CoA oxidase, the first enzyme of peroxisomal beta-oxidation (which catalyzes the side chain oxidation of THCA), was enhanced 15-fold in liver homogenates from clofibrate-treated rats when palmitoyl-CoA was the substrate, but the oxidase activity remained unaltered when THC-CoA was the substrate. In the perfused liver, oleate, infused after a wash out period of 60 min, markedly inhibited bile acid secretion. The results 1) suggest that fatty acids inhibit THCA metabolism both at the activation step and at the peroxisomal beta-oxidation sequence and that separate enzymes may be involved in both the activation and peroxisomal beta-oxidation of fatty acids and THCA and 2) raise the question whether fatty acids might (indirectly?) affect overall bile acid synthesis via their inhibitory effect on THCA metabolism. PMID- 3350809 TI - A structural domain of the covalent polymer globin chains of artemia. Interpretation of amino acid sequence data. AB - Artemia is unusual in having extracellular hemoglobins of Mr 260,000 comprising two globin chains (Mr 130,000), each of which is a polymer of eight covalently linked domains of about Mr 16,000. The amino acid sequence of one of these domains (E1) has been determined. It has 147 residues and Mr of 17,574 including heme. Sequence alignment revealed 19.0% identity with sperm whale myoglobin, whereas other vertebrate and invertebrate globins had between 13 and 24% identity. However, a much higher percentage of residues has a similar side chain character, suggesting that the domain E1 is very similar to other globins in showing the myoglobin fold. Template model building based on the known three dimensional structure of myoglobin further supports this conclusion. Conversely, the differences between E1 and other globins are believed to reflect differences in the packing of the domains, first in a covalent polymeric subunit containing eight hemes and subsequently by association of two of these subunits as dimers. These findings provide further evidence for the versatility of the myoglobin fold. PMID- 3350810 TI - Targeted antagonism of galactosamine toxicity in normal rat hepatocytes in vitro. AB - We present evidence that normal hepatocytes can be specifically protected from galactosamine toxicity in vitro by targeting an antagonist to these cells via receptor-mediated endocytosis. The strategy is based upon the following principles: 1) galactosamine is a highly selective hepatotoxin that causes a dose dependent depletion of uridine intermediates; 2) galactosamine toxicity can be antagonized by supplemental administration of uridine; 3) normal hepatocytes possess unique cell-surface receptors that can internalize galactose terminal (asialo-)glycoproteins with subsequent degradation of the glycoprotein ligand. Based on these facts, we hypothesized that chemical coupling of a galactosamine antagonist to an asialoglycoprotein could result in cell-specific delivery and protection of normal hepatocytes by targeting the antagonist via asialoglycoprotein receptors. Using a model system consisting of freshly isolated rat hepatocytes (receptor (+)) and Morris 7777 rat hepatoma (receptor (-)) cells, sensitivity to galactosamine in vitro was determined and found to be similar for both types of cells. A targetable antagonist was synthesized by coupling uridine monophosphate to asialoorosomucoid in a molar ratio of 5 to 1. Exposure of Morris 7777 cells to the targetable antagonist in the presence of a toxic concentration of galactosamine did not protect these cells as evidenced by a steady decline in the number of viable cells in a fashion identical to cells treated with galactosamine alone. However, normal hepatocytes that received the conjugate in the presence of galactosamine were protected as their viable cell number remained the same as control (untreated) cells. Competition by an excess of asialoglycoprotein inhibited the protective effect of the conjugate, supporting the concept that the asialoglycoprotein component of the conjugate was responsible for the specific delivery of the antagonist to the target cells. PMID- 3350811 TI - Conformation-sensitive modification of the type II calmodulin-dependent protein kinase by phenylglyoxal. AB - Chemical modification by phenylglyoxal was used to investigate relationships between the structure, function, and regulation of the type II calmodulin dependent protein kinase. Modification of the protein kinase by phenylglyoxal resulted in specific labeling of one distinct site, most likely an important arginine residue, with concomitant inactivation of the enzyme. Labeling and inactivation of the protein kinase was prevented by Mg2+-ADP which suggests that modification occurred at, or in close proximity to, its nucleotide-binding pocket. Half-maximal protection by Mg2+-ADP was enhanced by calmodulin which decreased the K0.5 for ADP from 540 to 61 microM. This response of the enzyme to calmodulin indicates that the modulator protein increases the affinity of the protein kinase for nucleotides. Inactivation of the enzyme by phenylglyoxal was dependent on the presence of Mg2+ or Ca2+/calmodulin, and further enhanced by the simultaneous addition of these effectors to the reaction. The Mg2+ effect is indicative of binding of this divalent metal ion to the protein kinase even in the absence of calmodulin and nucleotides. The stimulation of the modification reaction by calmodulin indicates an increase in the reactivity or accessibility of the modified residue in response to calmodulin-regulated conformational changes on the enzyme. The calmodulin-induced changes observed in this study may play important roles in the molecular mechanisms of activation of the type II calmodulin-dependent protein kinase. PMID- 3350812 TI - Energy requirements for diphtheria toxin translocation are coupled to the maintenance of a plasma membrane potential and a proton gradient. AB - Translocation of diphtheria toxin (DT) or ricin to the cytosol is the rate limiting step responsible for (pseudo) first-order decline in protein synthesis observed in intoxicated cell populations. The requirements for energy utilization in the translocation of both toxins are examined by perturbing the intoxication during this period of protein synthesis decline. Translocation of either toxin is blocked at 4 degrees C and requires energy. Ricin translocation is tightly coupled to ATP hydrolysis with no involvement of membrane potential. Cell depolarization slows the rate of DT translocation but does not block completely. Elimination of transmembrane pH gradients alone does not affect DT translocation; however, in combination with depolarization, translocation is blocked virtually completely. Energy requirements for DT intoxication are mediated by establishing a plasma membrane potential and a pH gradient across some cellular membrane. It is proposed that a postendocytotic vesicle containing processed DT fuses with the plasma membrane. Either component of the proton motive force across the plasma membrane then drives DT translocation. Ricin apparently utilizes a different energy coupling mechanism at a different intracellular site, thus demonstrating toxin specificity in the translocation mechanism. PMID- 3350813 TI - Characterization of rat skeletal muscle sarcolemmal insulin receptors and a sarcolemmal insulin binding inhibitor. AB - When insulin receptors of rat skeletal muscle sarcolemmal vesicles were solubilized with Triton X-100, the specific binding of 125I-labeled insulin increased by more than 10-fold over that seen in the intact vesicles. Partial purification of the skeletal muscle insulin receptors on wheat germ agglutinin affinity columns increased the total insulin binding activity by 7-fold and reduced the Kd for insulin binding from 1.92 to 0.20 nM, suggesting that an inhibitor of insulin binding was removed by this purification step. This was confirmed when the unbound fractions of the affinity column were dialyzed and reconstituted with the insulin receptors. The inhibitory activity in the sarcolemmal extract could not be accounted for by the presence of Triton X-100. The skeletal muscle inhibitor was more potent in inhibiting insulin binding to skeletal muscle insulin receptors than to liver or adipose receptors. The inhibitor was very effective in inhibiting insulin binding to wheat germ agglutinin-purified IM-9 receptors, but had negligible effects on insulin binding to intact IM-9 cells. The properties of the alpha and beta subunits of the skeletal muscle insulin receptors appear to be the same as those of insulin receptors of other tissues: cross-linking of 125I-labeled insulin to the receptor revealed a band of 130,000 daltons, and insulin stimulated the phosphorylation of bands of 90,000 and 95,000 daltons in the receptor preparation. The skeletal muscle insulin binding inhibitor elutes from molecular sieves in a major 160,000 dalton peak and minor 75,000-dalton peak. The binding inhibitor is not inactivated by heat, by mercaptoethanol, or by trypsin, pepsin, or proteinase K. Collectively, these data suggest that the inhibitor may be a small molecule that aggregates with itself, with larger proteins, or with detergent micelles. PMID- 3350814 TI - Localization of three distinct heparin-binding domains of laminin by monoclonal antibodies. AB - Monoclonal antibodies were utilized to localize novel heparin-binding domains of laminin. A solid-phase radioligand binding assay was designed such that [3H] heparin bound to laminin in a time- and concentration-dependent manner. Tritiated heparin binding to laminin was saturable and specific as determined by competition with unlabeled heparin, dextran sulfate, and dermatan sulfate. By Scatchard analysis, two distinct dissociation constants were calculated (Kd = 50 and 130 nM), suggesting the presence of at least two binding sites for heparin on laminin. Tritiated heparin bound to thrombin-resistant (600 kDa) and chymotrypsin resistant (440 kDa) laminin fragments, both known to lack the terminal globular domain of the long arm. Sodium dodecyl sulfate-polyacrylamide gels of chymotrypsin- and thermolysin-digested laminin chromatographed on a heparin Sepharose column showed multiple proteolytic fragments binding to the column. Monoclonal antibodies generated against laminin were tested for their ability to inhibit [3H]heparin binding to laminin. Four monoclonal antibodies significantly inhibited the binding of [3H]heparin to laminin in the range of 15-21% inhibition. Laminin-monoclonal antibody interactions examined by electron microscopy showed that one antibody reacted at the terminal globular domain of the long arm, domain Hep-1, while epitopes for two of these monoclonal antibodies were located on the lateral arms of laminin, domain Hep-2, and the fourth monoclonal antibody bound below the cross-region of laminin, domain Hep-3. When two monoclonal antibodies recognizing distinctly different regions of laminin were added concomitantly, the inhibition of [3H]heparin binding to laminin increased almost 2-fold. These results suggest that at least two novel heparin binding domains of laminin may be located in domains distinct from the terminal globular domain of the long arm. PMID- 3350815 TI - Lectin-like binding of pertussis toxin to a 165-kilodalton Chinese hamster ovary cell glycoprotein. AB - Chinese hamster ovary (CHO) cells cluster in the presence of pertussis toxin, a response that is correlated with the ADP-ribosylation of a Mr = 41,000 membrane protein by the toxin. A ricin-resistant line of CHO cells (CHO-15B) which specifically lacks the terminal NeuAc----Gal beta 4GlcNAc oligosaccharide sequence on glycoproteins did not cluster in response to pertussis toxin. These cells do contain the Mr = 41,000 protein substrate for the enzymatic activity of the toxin which suggests that pertussis toxin, like certain plant lectins, does not bind to or is not internalized by the CHO-15B cells. There was no evidence of pertussis toxin binding to gangliosides or neutral glycolipids isolated from CHO cells but the toxin bound to a Mr = 165,000 component in N-octyglucoside extracts of CHO cells that had been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted to nitrocellulose. Plant lectins from Ricinus communis and Erythina cristagalli detected a similar size band in CHO cells and also did not react with CHO-15B cells. Unlike pertussis toxin, these plant lectins recognized two other major bands in CHO cell extracts and reacted best after sialidase treatment of nitrocellulose transfers containing CHO cell extracts. Conversely, sialidase treatment abolished binding a pertussis toxin and wheat germ agglutinin, a plant lectin that reacts with multivalent sialic acid residues on glycoproteins, to the Mr = 165,000 band. Purified B oligomer of pertussis toxin also uniquely detected a Mr = 165,000 component in CHO cell extracts while the A subunit of pertussis toxin was unreactive. These results indicate that pertussis toxin binds to a CHO cell glycoprotein with N-linked oligosaccharides and that sialic acid contributes to the complementary receptor site for the toxin. In addition, they suggest that a glycoprotein may serve as a cell surface receptor for pertussis toxin and that this interaction is mediated by a lectin-like binding site located on the B oligomer. PMID- 3350816 TI - Wheat germ cytoplasmic ribosomes. Structure of ribosomal subunits and localization of N6,N6-dimethyladenosine by immunoelectron microscopy. AB - Cytoplasmic ribosomes have been isolated from wheat germ, and the structure of ribosomal subunits has been examined by electron microscopy of negatively stained preparations. Small (40 S) subunits show structural features generally regarded as characteristic of eukaryotic particles, while large (60 S) subunits show shapes that are equally well described by models of prokaryotic 50 S particles. Small subunit 18 S RNA contains 2 residues of N6,N6-dimethyladenosine 19 and 20 residues from the 3'-end (Hagenbuchle, O., Santer, M., Steitz, J. A., and Mans, R. J. (1978) Cell 13, 551-563). Nucleoside analysis by high performance liquid chromatography shows no other residues of this component in the RNA. Anti dimethyladenosine immunoglobulins were reacted with wheat germ 40 S subunits, and the resulting complexes were studied by electron microscopy in order to localize the nucleoside. In about 90% of the complexes observed, antibody-subunit contact was consistent with a single binding site. We place the dimethyladenosine residues at or near the end of the platform of the 40 S particle in a position nearly equivalent to that previously identified in prokaryotic and chloroplast subunits (Trempe, M. R., and Glitz, D. G. (1981) J. Biol. Chem. 256, 11873 11879). PMID- 3350817 TI - Wheat germ cytoplasmic ribosomes. Localization of 7-methylguanosine and 6 methyladenosine by electron microscopy of immune complexes. AB - Nucleoside analysis of the RNA from the small subunit of wheat germ cytoplasmic ribosomes shows 1 mol each of N7-methylguanosine and N6-methyladenosine/mol of RNA. Antibodies directed against each methylated nucleoside were used to localize these residues within the subunit by electron microscopy of immune complexes. Antibodies to 7-methylguanosine bound 40 S subunits at a single site, at or slightly above the division between the upper and lower segments of the particle and on the surface furthest from the platform (or large lobe) of the subunit. This site is essentially equivalent to that previously seen with Escherichia coli and chloroplast 30 S subunits (Trempe, M. R., Ohgi, K., and Glitz, D. G. (1982) J. Biol. Chem. 257, 9822-9829). Antibodies to N6-monomethyladenosine were induced in rabbits with a nucleoside-albumin conjugate and shown to be specific for the modified nucleoside. Electron microscopy of antibody-subunit complexes placed the methyladenosine residue in a position that is essentially indistinguishable from that of 7-methylguanosine. PMID- 3350818 TI - Properties of scrapie prion protein liposomes. AB - Purified scrapie prions contain one identifiable macromolecule, PrP 27-30, which polymerizes into rod-shaped amyloids. The rods can be dissociated with retention of scrapie infectivity upon incorporation of PrP 27-30 into detergent-lipid protein complexes (DLPC) as well as liposomes. As measured by end-point titration, scrapie infectivity was increased greater than 100-fold upon dissociating the rods into liposomes. The incorporation of PrP 27-30 into liposomes was demonstrated by immunoelectron microscopy using colloidal gold. Detergent extraction of prion liposomes followed by chloroform/methanol extraction resulted in the reappearance of rods, indicating that this process is reversible. Scrapie prion infectivity in rods and liposomes was equally resistant to inactivation by irradiation at 254 nm and was unaltered by exposure to nucleases. A variety of lipids used for producing DLPC and liposomes did not alter infectivity. Fluorescently labeled PrP 27-30 in liposomes was used to study its entry into cultured cells. Unlike the rods which remained as large fluorescent extracellular masses, the PrP 27-30 in liposomes rapidly entered the cells and was seen widely distributed within the interior of the cell. PrP 27-30 is derived by limited proteolysis from a larger protein designated PrP(Sc) which is membrane bound. PrP(Sc) in membrane fractions was solubilized by incorporation in DLPC, thus preventing its aggregation into amyloid rods. The functional solubilization of scrapie prion proteins in DLPC and liposomes offers new approaches to the study of prion structure and the mechanism by which they cause brain degeneration. PMID- 3350819 TI - Characterization of 69- and 100-kDa forms of 2-5A-synthetase from interferon treated human cells. AB - The existence of distinct 69- and 100-kDa forms of 2-5A-synthetase in addition to the smaller (40 and 46 kDa) forms has recently been established. Using specific monoclonal antibodies we investigated the induction, synthesis, and activity of 69- and 100-kDa 2',5'-oligoadenylate (2-5A) synthetases in interferon-treated human Daudi cells. Although induction of these synthetases is detectable in cells treated with as little as 1-5 units/ml of human alpha-interferon, higher concentrations are required for maximum synthesis of the 100 kDa than the 69-kDa protein. At 5 units/ml of interferon, enhanced synthesis of both proteins is detectable at 4 h with maximum synthesis occurring between 8 to 12 and 12 to 16 h for 69- and 100-kDa 2-5A-synthetases, respectively. At 24 h after addition of interferon, synthesis of these synthetases declines due to a decrease of active interferon in the culture medium. The synthesis of both synthetases is blocked by actinomycin D, and the half-life of these proteins is estimated to be 8 h. The activities of immunoaffinity purified 69- and 100-kDa synthetases are dependent on double-stranded (ds)RNA but show different requirements for optimum concentration of dsRNA and pH of the reaction. The apparent Km of 69- and 100-kDa synthetases for ATP is 1.7 X 10(-3) M and 3.6 X 10(-3) M, respectively. At optimum conditions for the activity of these enzymes, the pattern of 2',5'-linked oligoadenylates synthesized are different, the 69-kDa protein synthesizing higher oligomers than the 100-kDa species. Taken together, these results indicate that the 69- and 100-kDa 2-5A-synthetases are distinct proteins each with specific characteristics of induction and enzymatic activity. PMID- 3350821 TI - The stability and immunogenicity of a dispersed-grown freeze-dried Pasteur BCG vaccine. AB - The level of antituberculous immunity seems to be related to the number of memory T cells induced. This may vary as a function of the multiplication and persistence of BCG in host tissues. The most important requirements for a BCG vaccine are, therefore, the immunogenicity of the strain, the high proportion of live to dead bacilli, and adequate dispersion and low levels of soluble antigens. The surface-grown Pasteur BCG vaccine contains a very high proportion of bacilli killed by ball-milling and freeze-drying. It also contains clumps and soluble antigens, all factors influencing cell-mediated immune processes and viability control. Therefore, several batches of vaccine were prepared on an industrial scale using one of the most immunogenic strains (French 1173 P2) and grown as dispersed bacilli by a modified cell type culture method. This method provided fully viable, well-dispersed vaccines which have a viability and heat stability superior to that of the classical surface-grown BCG. The immunogenicity was checked by multiplication and persistence in mouse organs and the skin reactivity and tuberculin hypersensitivity in guinea-pigs showed results comparable to those obtained with classical vaccine. Small-scale tests in children showed superior immunogenicity of the dispersed as opposed to the classical vaccine and there was no suppurative adenitis. PMID- 3350820 TI - [Stability of a new thermostable 17D yellow fever vaccine]. PMID- 3350822 TI - The preparation of cultured rabies virus and the production of antiserum for human use. AB - In this paper we describe a methodology for the preparation of the Pasteur strain of fixed rabies virus in BHK-21 clone 13 cells and also its use for the production of antisera in horses. The methodology showed here is simple, rapid, facilitates the attainment of high protective titers, and the antisera produced are of high quality. PMID- 3350824 TI - Active and passive rabies immunization: the effect of administering hyperimmune globulin before the vaccine. PMID- 3350823 TI - Additives to biological substances. V--The stability of lactose as a carrier for Biological Standards. AB - The stability of freeze-dried lactose has been studied, by accelerated degradation, after being ampouled under the conditions employed for the preparation of International Standards and Reference Preparations and also under less stringent conditions which might facilitate degradation. The possible formation of the reactive product, 5-hydroxymethyl-furfural, has been monitored over a period of 10 years at temperatures up to 56 degrees C. No evidence has been obtained to suggest that the formation of this compound would present a hazard to the stability of standards prepared by the procedures customarily employed. PMID- 3350825 TI - Biomechanics of the arterial wall under simulated flow conditions. AB - A perfusion apparatus is employed to reproduce quantifiable pulsatile hemodynamics within freshly excised canine carotid arteries. From measurements of pulsatile intraluminal and transmural pressure and the dynamic radial motion of the vessel wall, calculations are made of the vascular incremental modulus of elasticity and hoop, axial, and radial wall stresses. The results of this investigation suggest that an increase in transmural pressure from 120/80 to 240/120 mmHg produces a marked elevation in incremental modulus and arterial wall stress. These parameters are reduced when transmural pressure is lowered while maintaining intraluminal pressure at physiologic values. PMID- 3350826 TI - Global mechanical consequences of reduced cement/bone coupling rigidity in proximal femoral arthroplasty: a three-dimensional finite element analysis. AB - Component loosening in total hip arthroplasty is often accompanied by substantial bony remodelling, associated initially with reduced stiffness of the cancellous bone bordering the cement, and eventually with the formation and proliferation of a compliant fibrous membrane at the bone/cement interface. An anatomically based three-dimensional finite element model has been developed to explore the salient stress changes occurring with progressive degradation of the stiffness of the cancellous bone in a thin zone bordering the cement. This border zone, modelled as a distinct linearly elastic and isotropic material layer, assumed a geometry and a range of mechanical properties inferred from eventual membrane thickness apparent in recent animal studies of component loosening. The major variables considered were: stiffness (elastic modulus) and compressibility (Poisson ratio) of the border zone, stiffness changes in the outlying cancellous bone, resultant hip contact force, and trochanteric muscle loadings. The results for the limiting case of a non-degraded border zone compared reasonably with previous studies of femoral reconstructions having rigid bone-to-cement attachment. Progressive decay of border zone stiffness produced complex changes in load transmission. Foremost among these were a generalized increase in stress levels (especially of transverse-plane tension) in the proximo-lateral cancellous bone, and a corresponding generalized decrease in stress levels in the proximo-medial cancellous bone. There were also large bending moment increases in the prosthesis and its cement mantle, especially at mid-stem. At almost all sites, the critical stress levels were those developed for peak stance-phase loading, rather than for the lower loads (and different resultant contact force directions) occurring elsewhere in the gait cycle. The elevated proximo-lateral cancellous bone stresses occurring with eventual membrane development, consistent with localized bony hypertrophy seen in recent animal studies, may be a response to hoop stresses occurring during pistoning of the tapered cement mantle. PMID- 3350827 TI - The effect of porosity and mineral content on the Young's modulus of elasticity of compact bone. AB - The Young's modulus of elasticity, the calcium content and the volume fraction (1 porosity) of 23 tension specimens and 80 bending specimens, taken from compact bone of 18 species of mammal, bird and reptile, were determined. There was a strong positive relationship between Young's modulus and both calcium content and volume fraction. A power law model fits the data better than a linear model. Young's modulus has a roughly cubic relationship with both calcium content and volume fraction. Over 80% of the total variation in Young's modulus in this data set is explained by these two variables. PMID- 3350828 TI - Influence of geometric taper on the derivation of the true propagation coefficient using a three point method. AB - We studied the effect of geometric taper on the derivation of the true propagation coefficient from three pressures determined 10 cm apart ('three-point method'). For this purpose the true propagation coefficients of a uniform latex tube (length 50 cm, outer diameter 12.73 mm, Womersley phase velocity 6.23-6.42 ms-1 (1-10 Hz), Womersley damping coefficient 0.05-0.14 m-1 (1-10 Hz) and of a tapered latex tube (length 50 cm, outer diameter varying from 15.88 to 9.45 mm, in the middle section with same properties as the uniform tube) were determined. The real part of the true propagation coefficient (the damping coefficient) was compared with apparent damping, and with the damping coefficient calculated using Womersley's theory. The imaginary part of the true propagation coefficient (the phase coefficient) was expressed in terms of phase velocity. True phase velocity was compared with measurements of apparent phase velocity, foot-to-foot velocity, and calculations of phase velocity parameters Womersley's theory and the Moens Korteweg equation. The results show that in the uniform tube the three-point propagation coefficient is in agreement with all other estimates. Taper causes an error in the three-point propagation coefficient. At some frequencies the damping is reversed to amplification (values up to -2 m-1) and the phase velocity may be both overestimated or underestimated (up to 50%). The overestimation of true damping as reported in the literature cannot be explained from vessel taper. PMID- 3350829 TI - On the dependence of the elasticity and strength of cancellous bone on apparent density. AB - This paper presents a statistical analysis of the pooled data from a number of previous experiments concerning the dependence of the Young's moduli and strength of cancellous bone tissue upon apparent density. The results show that both the Young's moduli and the strength are proportional to the square of apparent density of the tissue and are therefore proportional to one another. It is shown that the coefficient of proportionality is different for human and bovine tissue. It is concluded that the suggestion of Wolff (Das Gesetz der Transformation der Knochen, Hirschwald, Berlin, 1892) that compact bone tissue is simply more dense cancellous bone tissue is not an accurate statement when only the mechanical properties of these two tissues are considered. It is noted that estimates for the elastic modulus of the individual trabecula of human cancellous bone vary from 1 to 20 GPa and it is suggested that this question needs further study. PMID- 3350830 TI - Multichannel strain gauge telemetry for orthopaedic implants. AB - In vivo measurements of the loads and deformations occurring in orthopaedic implants will allow future improvements to be made. This paper describes an extremely small telemetry for long term measurements with three strain gauges and methods for an absolutely safe implant design. Developed for measuring the load at hip prostheses, the telemetry can also be used for other implants. Its size makes feasible instrumentation of devices with only slight mechanical modifications. In addition to the description of our own measuring system, the paper gives a survey on the problems of telemetrized implants, on methods for measuring spatial loads, and on the investigations of other authors. Future publications will present in vivo measurements with this telemetry, among others on hip endoprostheses. PMID- 3350831 TI - Biomechanical basis of optimal scoliosis surgical correction. AB - For an optimal approach to surgical correction of scoliosis, it was deemed desirable to biomechanically simulate the set of corrective forces applied by alternative internal fixation systems, so as to determine and apply the internal fixation system producing the best correction under safe levels of forces applied by the fixation systems to the spinal structures. To this end, we have developed, and presented here, (1) a spinal finite-element model relating the applied corrective forces to the corrected spinal configurations, (2) a method for determining the stiffness of the patient's spine prior to surgery, (3) computerized finite-element analysis simulation of alternative internal correction-fixation systems, so as to determine the most efficacious system, (4) instrumentations for surgically implementing the recommendations of the surgical simulation analysis and (5) comparisons of the model-simulated and surgically obtained corrected spinal configurations. These procedures together constitute the biomechanical foundations of scoliosis surgical correction. PMID- 3350832 TI - Influence of contractile tension development on dynamic strength measurements of the plantarflexors in man. AB - The influence of the contractile tension rise time on isokinetic force-angle records has been inferred from static force-time curves but has not been experimentally determined. The purpose of this study is thus to describe the influence of the contractile rise time on the force-angle curves produced during maximal voluntary, acceleration controlled, isokinetic plantarflexions at 30 degrees/s. Since we could not measure directly the period of force development unbiased by changes in muscle length during the movements, we devised an experimental strategy which allowed the computation of the dynamic force-time curve. Thus in five normal men, we first recorded force-angle curves produced during maximal voluntary plantarflexion movements preceded by maximal static pre loading (D:-10 degrees Max) in order to eliminate the period of tension development from the force-angle record. Next, we recorded force-angle curves produced during maximal voluntary contractions initiated from two different starting angles without pre-loading (D:-10 degrees Min and D:0 degrees Min) to include the period of tension rise. The dynamic force-time curve was computed by correcting these force-angle curves (D:-10 degrees Min and D:0 degrees Min) for the hypothetical loss in force due to muscle shortening. We compared the relative (to remove the effects of force magnitude) computed dynamic force-time curves with relative static force-time curves measured at three different angles. We found the shape and several other parameters of all three static and both computed dynamic force-time curves to be similar (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3350833 TI - On the flow characteristics of the renal artery transplants--model studies. AB - It is shown analytically and experimentally that, within the scope of a surgery, the effects of variations in the position of the transplant-aorta contact point (relative to the renal artery natural location), in the transplant departure angle (relative to the aorta), in the transplant length and in the transplant curvature are relatively insignificant regarding mean flow resistance. Hence, it is concluded that, from this point of view, it is not important how the transplant will be situated and that the space convenience should be the surgical determining factor. Nevertheless, it is also shown that the rate of blood flow to the kidney may be significantly curtailed if the selected transplant diameter is too small. However, it is indicated that the above may not constitute the only criterion. Since there exists a theory that the atherosclerotic formations begin and develop within the separation regions, additional research is suggested correlating separation regions with the variables indicated above. PMID- 3350834 TI - Cimetidine enhances cisplatin toxicity in mice. AB - The combination of the histamine H2 antagonist cimetidine (CMT) and the anticancer agent cisplatin (CDDP) was studied in normal and tumorbearing mice. CMT doses of 100 mg/kg produced no alteration in the survival of DBA/2J mice bearing P388 leukemia treated with CDDP doses of 3 mg/kg or 6 mg/kg. In these groups, the median survival was 13 days and 16 days, respectively, compared to 10 days in untreated controls. However, when adult CD-1 mice were given higher but nonlethal CDDP doses of 10, 15, or 18 mg/kg, the addition of CMT significantly increased CDDP lethality (P less than 0.05 by Wilcoxon analysis). For the 3 groups, CMT-enhanced lethality occurred in 10% of mice given 10 mg/kg CDDP, 80% of mice given 15 mg/kg, and 100% of mice given 18 mg/kg CDDP. Thus, CMT can acutely alter CDDP toxicity without affecting antitumor efficacy in mice. PMID- 3350835 TI - Tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene in mouse skin and rat mammary gland. AB - Studies of the tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene (BP) can provide evidence about the role of the 6 position in the carcinogenic activation of BP. Female Swiss and A-strain mice were treated on the skin with BP, 6-fluorobenzo[a]pyrene (6-FBP), 6-chlorobenzo[a]pyrene (6-C1BP), 6 bromobenzo[a]pyrene (6-BrBP) and 6-iodobenzo[a]pyrene (6-IBP) by repeated application, and in some cases by initiation-promotion. While BP was more potent than 6-FBP, only these two compounds exhibits tumor-initiating and carcinogenic activity in mouse skin. Female Sprague-Dawley rats were treated with BP, 6-FBP, 6 ClBP, and 6-BrBP by intramammillary injection. BP and 6-FBP induced high levels of mammary epithelial tumors and fibrosarcomas. 6-ClBP elicited only a high percentage of fibrosarcomas, whereas 6-BrBP induced a few adenocarcinomas. These results indicate that chloro or bromo substitution at C-6 in BP reduces or eliminates carcinogenic activity. Conversely, 6-FBP, from which the fluoro substituent has been chemically and metabolically removed by one-electron oxidation, displays a moderate carcinogenic activity which is consistent with activation by either one-electron oxidation or monooxygenation. PMID- 3350836 TI - Immunohistochemical localization of creatine kinase BB in primary breast cancer: correlation with estrogen receptor content. AB - The brain-type (BB) isoenzyme of creatine kinase (CK) has recently been shown to be estrogen-regulated in human breast cancer cells in vitro. In this study we have correlated the presence of CK-BB, evaluated by immunoperoxidase procedures, with the estrogen receptor (ER) content in 35 primary breast cancers. Of 35 tumors examined, 66% revealed moderate to strong CK-BB immunoreactivity. Staining was exclusively located in the cytoplasm of neoplastic cells. A positive relationship was observed between CK-BB positivity and ER content with ER-rich tumors (greater than 50 fmoles/mg protein) showing a more intense immunoreactivity than ER-poor ones. The results indicate that CK-BB is estrogen regulated in human breast cancer and suggest that evaluation of this enzyme may be of potential value for the detection of hormone responsive tumors. PMID- 3350837 TI - Role of recombinant interferon alpha 2 and cimetidine in patients with advanced malignant melanoma. AB - Following recent reports suggesting that the addition of cimetidine to interferon may enhance response rates in patients with metastatic malignant melanoma, we have completed a Phase II study of the use of recombinant alpha 2 interferon and cimetidine in patients with advanced malignant melanoma and who had progressive disease following interferon therapy alone. We observed two partial responses, no complete responses, and two patients had stable disease. Toxicity encountered was analogous to that of interferon alone. We conclude that the additional of cimetidine to alpha interferon is not beneficial in the treatment of advanced metastatic malignant melanoma. PMID- 3350839 TI - Carcinogenicity of aromatic hydrocarbons directly applied to rat mammary gland. AB - To obtain some initial evidence on the mechanism(s) of activation of PAH in rat mammary gland, we studied the carcinogenicity of a series of PAH directly applied to this tissue. A series of PAH which are or are not expected to be activated by one-electron oxidation because of their low or high ionization potential (IP), respectively, were tested. The compounds were dispersed as fine powders on an exposed mammary gland of female Sprague-Dawley rats. 5-Methylchrysene, dibenz[a,h]anthracene and benz[a]anthracene, which have relatively high IP, were inactive. In contrast, three PAH with relatively low IP, 7,12 dimethylbenz[a]anthracene, benzo[a]pyrene (BP), and 3-methylcholanthrene (MC), were potent carcinogens, 6-MethylBP, with low IP, and 7-methyl-benz[a]anthracene, with borderline IP, elicited only mesenchymal tumors, whereas BP 7,8-dihydrodiol and cyclopenta[cd]pyrene were inactive. A series of MC derivatives substituted at C-1 or C-2 was tested. Substituents at C-1, the position of activation in the one electron oxidation pathway, generally suppressed carcinogenic activity. Substitution at C-2 did not eliminate carcinogenic activity, with the exception of MC2-one. These results provide initial information suggesting that one electron oxidation may be a mechanism of activation for PAH in the mammary gland. PMID- 3350840 TI - Non-persisting early foci of altered hepatocytes induced in rats by N nitrosomorpholine. AB - Male Sprague-Dawley rats were treated for 7 weeks with 120 mg/l N nitrosomorpholine in their drinking water. At the end of the treatment period there were large numbers of enzyme-altered foci in the liver. During the following 10 weeks, the number of foci decreased significantly. This decrease in the number of enzyme-altered foci was due to the disappearance of a special type of focus. The typical features of these non-persisting foci were distinct enzyme histochemical and striking morphological alterations as well as the localization in or close to the third zone, as defined by Rappaport. In contrast to the simultaneously appearing persisting foci, the non-persisting foci were always glycogen-poor or totally glycogen-free. Signs of cell death were frequently found in or near this type of focus. After these non-persisting foci had disappeared, the total number of pre-neoplastic lesions obviously remained constant. We conclude that this disappearance of early appearing, severely altered foci is due to cell loss caused by the non-specific toxic effect of the carcinogen. PMID- 3350838 TI - Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of fluorinated derivatives of benzo[a]pyrene and 3-methylcholanthrene. AB - Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with benzo[a]pyrene (BP) and 3-methylcholanthrene (MC) derivatives. SENCAR mice were initiated with BP, 6 fluorobenzo[a]pyrene (6-FBP), 6-methylBP, 7-FBP, 8-FBP, 9-FBP, 10-FBP, or 10 azaBP and promoted with tetradecanoyl phorbol acetate. The same compounds plus BP 7,8-dihydrodiol were tested by intramammillary injection in female Sprague-Dawley rats. Tumor-initiating activity in mice and/or carcinogenicity in rats were observed for BP, 6-methylBP, 6-, 7-, 8-, and 10-FBP, whereas 9-FBP was inactive in both experiments and 10-azaBP was only marginally active in the mammary gland. BP 7,8-dihydrodiol was carcinogenic in rat mammary gland, although it was less potent than BP. MC, 8-FMC, 10-FMC, and 3-methylcholanthrylene were also tested in Sprague-Dawley rats by intramammillary injection. All compounds were carcinogenic, with MC displaying the most potent activity. The less potent carcinogenic activity of BP 7,8-dihydrodiol in the mammary gland, compared with BP, and the moderate-to-weak tumor-initiating and/or carcinogenic activity of 7-, 8-, and 10-FBP suggest that the bay-region diol-epoxide pathway does not play a significant role in the activation of BP in these two target tissues. Similarly, the carcinogenic activity of 8-FMC and 10-FMC, in which the bay-region diol epoxide pathway is blocked, suggests that this mechanism of activation is not important in the carcinogenicity of MC in rat mammary gland. PMID- 3350841 TI - Heterogeneity of biotransformation of fluoranthene in perifused liver cells. AB - Pathways of biotransformation of the carcinogenic polycyclic hydrocarbon fluoranthene in individual isolated perifused liver cells were delineated using noninvasive microfluorescence spectroscopic techniques. An example of heterogeneity of coupling between phase I and phase II enzymes detected in a population of beta-naphthoflavone-induced rat liver cells demonstrates the usefulness of the experimental model of perifused liver cells. PMID- 3350843 TI - Biosynthesis of pyrimidine nucleotides and level of cytochrome P-450 in rat liver and kidney after clofibrate administration (an in vivo study). AB - Like other lipid-soluble xenobiotics, clofibrate (ethyl-2-(4-chlorophenoxy)-2 methylpropanoate) increased the level of microsomal cytochrome P-450 in liver and decreased the utilization of 14C-orotic acid for the synthesis of hepatic cytidine nucleotides. This phenomenon was associated with the increased (a) uptake of 14C-cytidine, (b) total content of cytidine components of the acid soluble extract and (c) utilization of this nucleoside for the synthesis of RNA. No changes were observed in uridine components. Clofibrate also increased the level of cytochrome P-450 in kidney microsomes; the degree of induction was almost the same as in the liver. The variations of renal pyrimidine metabolism after administration of the drug were analogous to those observed in the liver. PMID- 3350842 TI - Mechanism of liver-specific metastatic tumor spread in a murine tumor model. AB - Malignant tumors frequently show an organ-specific metastatic spread, the causes of which are still largely unknown. Using an experimental tumor model, a methylcholanthrene-induced pleomorphic myofibrosarcoma ER 15-P of the C57Bl6J mouse, we wanted to find out whether this phenomenon is due to an adaptation or to a selection of tumor cells. After i.v. injection of tumor cells from the primary ER 15-P into the tail vein of male mice, metastases were regularly found in the lungs, mediastinal lymph nodes, and brain, as well as in the liver and kidneys, and occasionally in the adrenals. The following experimental procedures were used to isolate a tumor cell line with a possible liver preference: (1) Tumor cells from the primary ER 15-P were injected into a mesenteric vein of male mice. Tumor cells from the resulting liver colonies were again injected into the portal system of one group of mice. In a second group, part of the same cell suspension was injected into the tail vein. This procedure was performed four times. (2) Tumor cells from the primary ER 15-P were applied into the tail vein of male mice. Tumor cells from the resulting liver metastases were reinjected directly into the tail vein. This experiment was repeated three times. (3) Tumor cells from the primary ER 15-P were injected into the tail vein of male mice. Tumor cells from liver metastases were then injected, first, into the portal system of one group of male mice, and thereafter into the tail vein of another group of animals. This experiment was repeated twice. The following results were obtained: (1) By a repeated adaptation of tumor cells from the primary ER 15-P to liver tissue, no tumor cell line could be isolated that would show a preferential metastatic spread to this organ after tail-vein injection. (2) Repeated i.v. passages of tumor cells from liver metastases into the tail vein led to the selection of a tumor cell line with a tendency to liver metastasis. (3) Tumor cells selected from liver metastases induced via tail-vein injection showed, after a prolonged stay in the liver and a successive i.v. passage into the tail vein, a marked specificity for this organ. These results indicate that the liver specific spread of tumor cells in our model is based on the selection of a tumor cell line from the primary ER 15-P influenced by the hepatic microenvironment. PMID- 3350844 TI - Biochemical effects of methyl chloride in relation to its tumorigenicity. AB - The biochemical effects of methyl chloride were investigated in tissues of F-344 rats and B6C3F1 mice (both sexes). Activities of GST were 2-3 times higher in livers of male B6C3F1 mice, compared with those of female mice, and with rats of both sexes. In kidneys GST activities of (male) mice were about 7 times lower than those found in livers. The activity of FDH was higher in livers of mice (both sexes) than in those of rats. No obvious sex difference was found in livers of rats and mice with respect to FDH. In kidneys, however, (minor) differences in FDH activities occurred between male and female B6C3F1 mice (4.7 vs. 3.1 nmol/min per mg). Sex differences of FDH activity in kidneys were not observed in F-344 rats. The microsomal transformation (by cytochrome P-450) of methyl chloride and S-methyl-L-cysteine to formaldehyde in tissues of B6C3F1 mice occurred preferentially in the liver. More formaldehyde was produced in liver microsomes of male, compared to those of female mice. Kidney microsomes metabolized methyl chloride to formaldehyde much less than liver microsomes. After a single exposure of mice of both sexes to 1000 ppm methyl chloride no elevation in formaldehyde concentrations was observed in livers and kidneys ex vivo. The determination of DNA lesions, using the alkaline elution technique, revealed no DNA-protein crosslinks in kidneys of male B6C3F1 mice after exposure to methyl chloride (1000 ppm, 6 h day-1, 4 days) and gave only minor evidence of single-strand breaks. Lipid peroxidation (production of TBA reactive material), induced by single exposure to methyl chloride (1000 ppm, 6 h), was very pronounced in livers of male and female mice. Smaller increases in peroxidation were observed in the kidneys of exposed mice. The theory that renal tumors observed in male mice after chronic exposure of the test animals to high (1000 ppm) concentrations of methyl chloride, are evoked by intermediates and in situ produced formaldehyde is proven unlikely by our results. PMID- 3350845 TI - Correlation between size and external temperature in four rat tumours after treatment with cytostatic agents. AB - The reduction in size of four experimental tumours (ISIS 130 and ISIS 208 immunocytomas, S 437 mammary adenocarcinoma, S 447 colon adenocarcinoma) was investigated in LOU rats under the influence of cytostatic agents belonging to different classes (5-fluorouracil, methotrexate, vinblastine, cisplatin, doxorubicin, cyclophosphamide). External tumour and rectal temperatures were measured at the same time, twice daily, during the whole experiment. With the rectal temperature of the rats kept constant, the reduction in tumour dimensions following chemotherapy correlated via a linear relationship with the duration and degree of tumour hypothermia for the three tumours S 437, ISIS 208, ISIS 130. However, for the same reduction in tumour volume following chemotherapy, the duration and degree of transient tumour hypothermia varied according to the type of tumour and cytostatic agent studied. There was not correlation between the decrease in size of S 447 and external tumour hypothermia. Even when the reduction in tumour size was statistically significant, the hypothermic tumour phase after drug administration was not sufficient to be significant, except for vinblastine. However, the temperature of this slowly growing tumour before chemotherapy was particularly low. The measurement of the degree and duration of external tumour hypothermia of tumours following chemotherapy would represent a new physiological technique for measuring the efficacy and duration of action of cytostatic agents. PMID- 3350846 TI - Thrombin: implications for intratumor therapy against metastasis. AB - The effect of an intratumor injection of thrombin as a potential cancer therapeutic agent was examined in two transplantable solid tumor models: a renal adenocarcinoma implanted beneath the kidney capsule in Wistar-Lewis rats and a rhabdomyosarcoma implanted similarly in Wag-Rij rats. For each tumor type, a group of test animals received a single dose of thrombin injected directly into the central tumor mass 6 weeks following tumor implantation. Corresponding groups of tumor-implanted controls consisted of animals that received an equal volume injection of saline instead of thrombin and animals that were not injected. The tumor-implanted animals receiving thrombin, saline, or no injection were handled identically. The saline-injected and noninjected control animals died of metastasis to the lung within the same well-defined period of time. All animals receiving thrombin showed significantly increased longevity, and the degree of increase was related to variations in tumor size at the time of injection. In every case, animal death was due to pulmonary metastasis verified at autopsy, but animals receiving thrombin therapy lived about 85% longer following tumor implantation than animals not receiving therapy. PMID- 3350847 TI - In vitro malignant transformation of in vivo ENU-induced rat ovarian Sertoli cell tumor (adenoma). AB - An N-ethyl-N-nitrosourea-induced rat ovarian Sertoli cell tumor was grown in tissue culture in Dulbecco's modified Eagle's medium (DMEM) supplemented with 25% horse serum (HS) and a hormone combination of 20 ng/ml each of hydrocortisone, insulin, and prolactin. This tissue culture derived from a nonsteroid hormone producing tumor. Cytofluorometry and karyotyping of the nonhormone-producing tumor cell line (SCTL-1) revealed a diploid pattern for the early passage (P1), which became hyperdiploid (P10), and then aneuploid (P20). These cells had an epitheloid pattern, grew in a monolayer at early passages. After P10 the cells were transplanted into newborn rats and nude mice and resulted in high incidences of tumors (up to 100%). The cell line (SCTL-1) continued to grow in DMEM, 10% HS, and no hormone supplementation after P10. This study revealed that a benign rat ovarian Sertoli cell tumor after multiple passages in vitro underwent sequential genotypic and phenotypic changes and became highly malignant. PMID- 3350848 TI - Investigations on metabolism and carcinogenicity of 1,1,2-trichloroethane. AB - Two groups of male and female Sprague-Dawley rats (50 animals/group per sex) were treated with either 15.37 or 46.77 mumole of 1,1,2-TCE in DMSO/rat for 2 years. The animals were treated once a week by s.c. injection of test compound in the skin of neck. Two groups of controls received either DMSO or no treatment at all. The incidence of benign mesenchymal and epithelial tumors was not significant when compared with either DMSO-treated or untreated controls. The animals treated with 46.77 mumole 1,1,2-TCE significantly developed sarcomas when compared with the untreated controls. In a further experiment, either 40 mumole or 160 mumole 1,1,2-TCE was injected into male Wistar rats and the metabolites, TdGA and HEMA, were determined in 24-h urine samples. Comparative studies were carried out giving equimolar amounts of chloroethanol and 2-chloroacetaldehyde diethyl acetal. Analysis of the metabolites showed that no detectable HEMA was excreted in urine after treatment of rats with 1,1,2-TCE or chloroethanol. TdGA was excreted in urine much more among chloroacetaldehyde-treated animals than among 1,1,2-TCE- or chloroethanol-treated rats. PMID- 3350849 TI - The influence of the microenvironment of liver-specific tumor cell colonization in a murine tumor model. AB - Malignant tumors often show an organ-specific metastatic spread. Some cells of the primary apparently bear an affinity for growing in the microenvironment of certain organs. After i.v. injection of myofibrosarcoma cells from the primary ER 15-P into the tail vein of male C57/Bl6J mice, metastases developed in various organs. A tumor cell line (ER 15-Me3) isolated from liver metastases of the primary was found to colonize preferentially to the liver. To find out whether the liver specificity of the tumor cell line ER 15-Me3 depended on the hepatic microenvironment, tumor cells from this line were transplanted i.m. into the thighs of mice once (ER 15-Me3 i.m.1) or 5 times (ER 15-Me3 i.m.5), and then injected into the tail vein of mice. A part of the 5-times passaged tumor cell line was also injected into the mesenteric vein (ER 15-Me3 i.m.5-Me1) prior to reinjection into the tail vein. RESULTS: After i.v. administration of tumor cells from the first i.m. passage of the tumor cell line (ER 15-Me3 i.m.1) into the tail vein, the liver-specific metastatic behavior of tumor cells remained stable. Following the i.v. injection of tumor cells from the 5th i.m. transplant generation of the tumor cell line (ER 15-Me3 i.m.5) into the tail vein, organ distribution was similar to that of the primary. After only 1 mesenteric vein passage of the 5-times i.m. transplanted line ER 15-Me3 i.m.5-Me1 followed by i.v. injection into the tail vein, did tumor cells regain their liver-specific colonizing potential. Thus, the liver-specific tumor cell line seems to contain a small number of other tumor cell populations from the unselected primary. In the muscle, these tumor cells have a growth advantage over the liver-specific cells, while the latter will grow better in the liver. This indicates that the microenvironment may be one important factor influencing the organ-specific metastatic pattern of tumor cells. PMID- 3350850 TI - A simple method of delayed processing of tumor tissue in a soft agar clonogenic assay. AB - Sarcoma 180 tumor tissue from C57 mice was processed in a soft agar clonogenic assay immediately after removal from the animal and after various methods of storage. The sensitivity to the antineoplastic drug cis-platinum was not affected by different storage methods. The highest yield of colony forming cells per 100 mg tumor tissue was 2.3 X 10(4) cells following immediate processing of fresh tumor material. A 24-h storage of solid tumor tissue at 4 degrees C as well as cryopreservation of solid tumor tissue or cryopreservation of a single cell suspension prepared from fresh tumor specimens were found to reduce this value to 24%-37%. Storage of a tumor single cell suspension for 24 h at 4 degrees C however, proved to be a useful and simple method of delayed processing of tumor in a soft agar clonogenic assay. The observed cell yield was 1.91 X 10(4) colony forming cells, 83% of the immediately processed value. If this procedure is suitable for use with human tumor material obtained from biopsies and surgery, the 24 h time interval would be useful for transport from hospital to an appropriate special laboratory. This would result in the broader application of the human soft agar clonogenic assay in predictive testing and drug screening. PMID- 3350851 TI - No relevant influence on overall survival time in patients with metastatic breast cancer undergoing combination chemotherapy. AB - The results of clinical studies dealing with first and second line chemotherapy of metastatic breast cancer published between 1975 and early 1986 which involved 9350 women were reviewed. Our special aim was to evaluate combination chemotherapy and its influence on overall survival in late stage breast cancer patients. No significant improvement in overall survival times was found in this selected group of patients who were treated with intense palliative chemotherapy. PMID- 3350852 TI - Natural killer cell activities of patients with breast cancer against different target cells. AB - Natural killer (NK) cell activity against K 562 erythroleukemic- and MCF-7 breast carcinoma-derived cells was monitored in short-term (3 h/K 562) and long-term (18 h/MCF-7) chromium release tests for 60 patients with untreated primary breast disease. Target cell lysis was the same for patient groups with benign (n = 13) and malignant (n = 47) breast disease (27% versus 36% mean chromium release; target:effector ratio 40:1 for K 562 and 28% versus 40% for MCF-7 cells). NK activity as defined by short-term lysis of K 562 cells did not correlate with MCF 7 cell lysis in long-term assays for the carcinoma patients. This functional heterogeneity of natural cytotoxic activities of breast cancer patients was confirmed by a different age distribution for K 562 and MCF-7 cell lysis and high levels of MCF-7-directed NK activity in the grade I tumor group (56.2%). Our results indicate that measurement of peripheral blood NK activity against a breast carcinoma-derived cell line (MCF-7) defines a disease-related natural cytotoxic activity which correlates better with prognostic tumor parameters (tumor grading) than NK activity as defined by the lysis of K 562 erythroleukemic cells. NK activity testing against breast carcinoma cell lines should be used to monitor natural cytotoxic activities in breast cancer patients and its modulation by different routes of treatment. PMID- 3350853 TI - Effectiveness of mitoxantrone on the proliferation of cell cultures derived from malignant mesenchymal tumors of human origin. AB - The antiproliferative potency of mitoxantrone (MITOX) has predominantly been established for epithelial and hematologic neoplasias. In this study the effectiveness of MITOX was investigated in vitro for 6 sarcomatous human cell lines derived from 2 synovial sarcomas, a malignant schwannoma, a malignant histiocytoma, a leiomyosarcoma, and a chondrosarcoma. The examination was performed using a proliferation assay with monolayer cell cultures. The effect of MITOX was compared with that of adriamycin (ADR) and cisplatin (CDDP). For each drug at least 3 concentrations were tested which covered the therapeutically achievable range, i.e., for MITOX 0.2-0.002 micrograms/ml, for ADR 0.5-0.005 micrograms/ml, and for CDDP 5.0-0.05 micrograms/ml. Test incubations were performed for 3 days. Antiproliferative potency of the cytostatic drugs was assessed by counting the number of cells at the start and the end of the test period with and without drug addition. Furthermore the dose inhibiting cell growth to 50% of controls (ID50) was determined for MITOX. For comparison 4 cell lines from carcinomatous lesions were included in the study. MITOX inhibited proliferation rates of 4 sarcomatous tumor cell lines more intensively than ADR, and was less effective in 2 cell lines. However, these differences were not significant. In all mesenchymal cell lines tested the antiproliferative potency of MITOX was more pronounced than that of CDDP. In carcinomatous cell lines the MITOX-induced growth inhibition was similar to that found in response to administration of ADR and CDDP confirming the described effect on epithelial tumors. The study suggests that MITOX possesses a growth inhibitory potency for malignant soft tissue tumors in vitro. From these data it may be worthwhile to initiate clinical trials testing the treatment of sarcomatous lesions with MITOX. PMID- 3350854 TI - Serum antibodies to a normal cellular protein (P-65) in patients with Hodgkin's disease. AB - Samples from the L-428 Hodgkin's cell line and from several other lymphoma cell lines were lysed and the soluble proteins were subjected to one- or two dimensional gel electrophoresis. The separated proteins were transferred to nitrocellulose by the Western Blot technique; antibody reactivity was detected by an immunoperoxidase reaction. Of 152 sera from patients with Hodgkin's disease (HD) 26 (17%) reacted with protein P-65 whereas in the control group, consisting of 35 healthy persons and 20 patients with other malignant diseases only 1 serum was reactive. Thus, the difference between the two groups was highly significant (P less than 0.01). These antibodies were most common in stage III HD. Splenectomy had no effect on the incidence of these antibodies, and there seemed to be no correlation with B-symptoms or with the histological subtype. PMID- 3350855 TI - Androgen receptors in colorectal adenomas. AB - To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17-2.7 X 10(-9) M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P = 0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24-3.1 X 10(-9) M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process. PMID- 3350856 TI - Absence of in vitro mutagenicity of the fluid from breast cysts of women with macrocystic disease. AB - Cystic fluid from 30 Greek women suffering from macrocystic disease was tested for mutagenicity in the Salmonella typhimurium mutagenicity assay using three bacterial strains in the presence or absence of liver homogenate. None of the samples tested showed mutagenic potential in this test supporting the absence of potential carcinogens in the cyst fluids. PMID- 3350858 TI - Myogenic stem cell commitment probability remains constant as a function of organismal and mitotic age. AB - Chicken myogenic stem cells can undergo symmetric and asymmetric cell divisions. Symmetric divisions produce two stem cells or two cells committed to terminal muscle differentiation. Asymmetric divisions produce one stem cell and one committed cell. Committed cells undergo four divisions, and their progeny differentiate into postmitotic, biochemically distinct muscle cells, which can be identified immunocytochemically. The control of stem cell commitment was investigated in vitro by means of cell cloning and subcloning experiments, and computer modeling. We found that stem cell commitment is a process which can be modeled as a stochastic event, with a central tendency or probability of 0.2 +/- 0.1. This value is independent of organismal or mitotic age of the stem cells, cell density, or growth in a mitogen-poor environment. Myogenic stem cells stop dividing after approximately 30 divisions in vitro. Since the probability of commitment to terminal differentiation remains below 0.5, clonal senescence and terminal differentiation are separate processes in this system. PMID- 3350857 TI - Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix. AB - Freshly isolated adult rat hepatocytes, when cultured on type I collagen (commercially available as Vitrogen), assume a polygonal shape, form a stable monolayer within 24 hours, but lose the capacity to express some liver-specific functions over time in culture. We incubated hepatocytes in a serum-free medium on a reconstituted basement membrane gel, "matrigel" (prepared from an extract of extracellular matrix of the murine Engelbreth-Holm-Swarm sarcoma), and observed that the cells adhered firmly, remained rounded as single cells or clusters, and maintained liver-specific gene expression for more than 1 week in vitro. Hepatocytes on matrigel secreted substantially higher amounts of albumin, transferrin, haptoglobin, and hemopexin, Northern blot analyses of extracted cellular RNA, expressed increased amounts of mRNA for the liver-specific protein albumin (as compared with cells on vitrogen). In cultures treated with phenobarbital, cytochrome P-450b, and cytochrome P-450e, mRNAs and proteins were barely detectable in cells on Vitrogen but were induced to levels similar to those in the liver in vivo in matrigel cultures. Likewise, the use of matrigel greatly enhanced the induction of mRNA and protein for P-450c by 3 methylcholanthrene and for P-450p by steroidal and nonsteroidal inducers. However, neither substratum permitted induction of P-450d by 3 methylcholanthrene, suggesting that the effects of matrigel are selective even for expression in liver of members of the superfamily of cytochrome P-450 genes. Within 5 days in cultures on Vitrogen, hepatocytes expressed detectable amounts of fetal liver aldolase activity and also mRNA for vimentin and type I collagen, each considered a phenotypic change reflecting hepatocyte "dedifferentiation." None of these was present in cells on matrigel. Responsiveness to mitogenic stimuli, as judged by incorporation of 3H-thymidine into DNA, was also decreased in hepatocytes cultured on matrigel. Finally, there was a remarkable increase in the levels of both matrices during the first 2 days in culture. However, the continuously cytoskeleton mRNA over time in culture than did the rounded cells on matrigel. We conclude that hepatocytes cultured on matrigel, as opposed to the standard collagen, exhibit remarkably enhanced expression of many liver-specific functions. PMID- 3350859 TI - Characterization of functional histamine H1 receptors on a cultured smooth muscle cell line. AB - Cultured cells of the smooth muscle line DDT1MF-2, which was derived from a hamster vas deferens tumor, expressed histamine H1-type receptors and responded biochemically and functionally to H1-specific stimulation. The H1-receptor antagonist [3H]-pyrilamine bound specifically to 9.7 x 10(6) sites/DDT1MF-2 cell with a dissociation constant (Kd) of 219 nM. The addition of histamine to suspensions of fura-2-loaded DDT1MF-2 cells elicited a rapid, transient, and stimulus concentration-dependent increase in the intracellular concentration of Ca2+ with an EC50 of 3 x 10(-5) M, which demonstrated H1 receptor specificity. Moreover, in order to evaluate in vitro contractile response of individual DDT1MF 2 cells, the degree of intracellular actin polymerization was quantified by a DNase inhibition assay. The percentage of nonpolymerized or G-actin in DDT1MF-2 cells was reduced in a histamine concentration-dependent manner with an EC50 of 1 x 10(-5) M and H1 receptor specificity. Histamine-induced actin polymerization was accompanied by changes in cell shape that were consistent with cellular contraction, as assessed by flow cytometry. The H1-type receptors of cultured DDT1MF-2 cells thus couple histamine stimulation to a variety of functional responses of smooth muscle cells. PMID- 3350860 TI - Direct effects of wheat germ agglutinin on inositol phosphate formation and cytosolic-free calcium level in intestine 407 cells. AB - The interaction between dietary lectins, especially wheat germ agglutinin (WGA), and intestinal cells has been implicated in the pathogenesis of celiac disease. The present study was undertaken to investigate the immediate effects following such an interaction. Direct WGA-stimulation of Intestine 407 cells leads to an immediate rise in the cytosolic-free calcium concentration. The major part of this lectin-induced rise is due to an influx of calcium across the plasma membrane into the cytosol. However, WGA-exposure also results in an immediate mobilization of calcium from intracellular stores, most likely mediated via the simultaneous increase of inositol trisphosphate formation in these cells. The transduction mechanism described for WGA in these intestinal cells is not very sensitive towards pertussis toxin, indicating that if a G-protein is involved, it differs from those of most other systems. The suggested role for WGA in changing the functional and structural properties of intestinal cells might involve increases of inositol phosphate and cytosolic-free calcium levels. PMID- 3350862 TI - Automated classification of candidate structures for computer-assisted structure elucidation. AB - In computer-assisted structure elucidation, a large number of candidate structures for the unknown compound can be generated. A computer program designed to aid in the recognition of significant differences between these structures is described. The goal of the program is to group the candidates into meaningful classes with a minimum of input from the user; each class is distinguished by a substructure its members have in common. A computational approach is developed based on the combinatorial problem of set covering. The program evaluates its results using an information-theoretical criterion. An application of the program to a real-word structure problem is presented. PMID- 3350861 TI - Effect of nicotine on transferrin binding and iron uptake by cultured rat placenta. AB - The effect of nicotine on transferrin and iron transport in placental cells has been studied. Nicotine inhibits iron uptake but has little effect on the steady state levels of transferrin. The effect is temperature and concentration dependent and is not reversible. At a concentration of 15 mM nicotine inhibited transferrin endocytosis by 40%, while iron uptake was decreased by nearly 60%. Nicotine exerted a similar effect on reticulocytes, but other amines, either tertiary or quaternary, had little or no effect on either iron uptake or steady state intracellular transferrin levels. The results suggest that nicotine acts by blocking uptake, probably by acting as a weak base inhibiting iron release from transferrin, and inhibiting exocytosis with a resultant block of endocytosis. The concentrations required to exert an effect are too high to implicate inhibition of iron transport in the effects of smoking on pregnancy. PMID- 3350863 TI - [Combined surgery of subrenal aorta and renal arteries]. AB - Frequency and place of renal artery surgery during reconstructive aorto-iliac operation are discussed in relation to 25 patients operated upon between 1980 and 1986, these representing 4.1% of cases undergoing aorto-iliac surgery during the same period. Aortic lesions included 6 aneurysms of infrarenal aorta and 18 stenotic and/or occlusive lesions: 16 stage II, 1 stage III and 1 stage IV. Renal artery repair was for renovascular hypertension (13 cases), for renal prophylaxis (6 cases) and for technical reasons (5 cases), and consisted of direct reimplantation (3 cases), thrombo-endarterectomy (5 cases, including 2 trans aortic by thoracolumbar approach) or bypass (18 cases, including 11 venous grafts 3 in a same patient - and 7 prostheses). In contrast to literature data reporting an intraoperative mortality of between 6.8 and 12% no postoperative death occurred in this series. Morbidity observed was 2 asymptomatic postoperative renal thromboses, 1 stenosis of marked degree of a renal artery after trans aortic disobstruction treated successfully by endoluminal dilatation and finally, one case of acute renal insufficiency becoming chronic. No early or late complications were related to repair surgery to aorta and to lower limbs. Long term results were comparable with those of other series, with recovery from hypertension in 15.3% of cases, improvement in 46.1% and persistence in 38.4%. The lack of mortality in this short series has led to wide indications for combined aortic and renal surgery, but definitive conclusions cannot be drawn because of the small number of patients treated. PMID- 3350864 TI - [Traumatic lesions of the supra-hepaticocaval veins or lessons from failure. Apropos of 5 cases]. AB - Strategic therapeutic principles in 5 cases of injury to supra-hepaticocaval veins were based on vascular exclusion of liver prior to any approach to the lesion. An approach to the intrapericardial inferior vena cava by sternotomy is proposed together with the use of an endocaval shunt introduced through the atrium. PMID- 3350865 TI - [The role of resorbable mesh in the treatment of postoperative eventrations]. AB - Between the simple parietoplasties reserved for small eventrations and the insertion of non-resorbable prostheses, veritable "second" walls for large parietal defects, the place of a resorbable prosthesis is still open to debate. The latter acts, in fact, as a temporary internal contention at a time when the wall is weakened by the repair operation and is exposed prematurely to recurrence. A true "reinforced parietoplasty", this technic was used in 42 patients over" the last four years, without mortality or infectious complication and with only one partial recurrence after a mean follow up of 28 months. PMID- 3350866 TI - [Study of the annual mortality statistics in a general surgical ward with digestive and vascular orientation at a general hospital center]. AB - Quality of care has been evaluated in this study by the criterion of mortality in a Digestive and Vascular Surgery unit. The analysis over a one-year period concerned 34 dead patients among 1298 entered and 1,108 operated patients who underwent 1,248 operations. The causes of death have been studied in the 3 groups: non operated (5 patients), digestive (20 patients), vascular (9 patients), with distinction of emergency surgery. Therapeutic habits have been systematically reexamined and considered either adapted or to be modified. Punctual conclusions of such a study are interesting for the medico-surgical team but also for the nursing team. Transparency of mortality for a whole team is a factor of progress by the periodical reappraisal of the therapeutic habits based upon accurate data, and by the better collaboration in the team. PMID- 3350867 TI - [Antibiotic prevention and appendectomy. Practical consequences for health economics. Apropos of a series of 642 cases]. AB - A total of 642 patients undergoing appendicectomy were divided into two groups of 321 patients prior to surgery. One group (A) received prophylactic antibiotic therapy, the other (B) no previous treatment. Patients were from the same region and groups were comparable for age, sex and indications for operation. Antibiotic treatment was administered according to a personal protocol based on gross appearance of appendix, and involved two molecules: Baypen in 69 cases and cephamycin (Mefoxin) in the other 252. Although not a randomized trial, the protocol was considered effective for prevention of postoperative infectious complications. In the group A, 21 patients (6.54%) developed these complications as against only 3 (0.93%) in group B, a significant difference if the total group B is considered or the two antibiotic subgroups. However, no valid conclusion can be drawn in favor of one or other of the two molecules. This effective procedure reduces by a half the duration of postoperative hospital stay for patients with a simple acute or a chronic appendicitis accepting the follow up surveillance required by the protocol. This attitude should be extended to a larger number of patients with resulting non-negligible health costs economy. PMID- 3350868 TI - [Reoperations for early thromboses of femoropopliteal and tibial artery bypass. Apropos of 50 cases]. AB - The mechanism of thrombosis early after subinguinal bypass and outcome after revision surgery have been rarely analyzed. Results are reported of revision surgery for early thrombosis in 50 cases (10% of subinguinal bypass operations during the same period). Initial indication in the 40 men and 9 women (mean age 66.9 +/- 1.74 (SEM) years), was severe chronic or acute ischemia in 82%. The 50 thrombosed bypasses included 40 femoropopliteal, 8 femorotibial and 2 short bypasses. The bypass was by saphenous in situ (21 times), an inversed saphenous (9 times), a mixed bypass (12 times) and a prosthesis (8 times). The distal arterial bed was evaluated as good in 50% of cases. Analysis of cause of thrombosis, of the operative procedure and of the time before surgery enabled a technical cause to be determined in 31 of the 50 cases. Corrective surgery produced 16 permeable bypasses and 34 definitive thromboses complicated by 21 amputations and a 10% mortality. Improved results were related to a venous bypass (p less than 0.05), to a time before operation of less than 24 hours (p less than 0.02) and to a good distal bed. The 1 year actuarial permeability for the 50 bypass operations was 35%. Mixed bypass procedures and technical problems during surgery appear to be the principal predisposing factors of early thrombosis. In this series, the preoperative distal pressure index and intraoperative flowmetric recordings were not reliable predictive elements. PMID- 3350870 TI - [Use of the placenta in experimental vascular microsurgery]. PMID- 3350869 TI - [Adrenal metastasis of colonic adenocarcinoma]. PMID- 3350871 TI - [Simplified technic of implanting a catheter in a case of single right hepatic artery]. PMID- 3350872 TI - Infant vocalizations and changes in experience. PMID- 3350873 TI - Count/mass category acquisition: distributional distinctions in children's speech. PMID- 3350874 TI - Cue validity in Hebrew sentence comprehension. PMID- 3350875 TI - Children's understanding of the speech act of promising. PMID- 3350876 TI - Between-word processes in child phonology. PMID- 3350877 TI - Overextensions in early language comprehension: evidence from a signal detection approach. PMID- 3350878 TI - Linguistic input and early word meaning. PMID- 3350879 TI - Children learn from speech not addressed to them: the case of personal pronouns. PMID- 3350880 TI - Errors in computation of WISC and WISC-R intelligence quotients from raw scores. AB - Twenty-four per cent of 457 sequential IQ assessments contained errors in the calculation of verbal, performance or full scale IQ's from the raw scores; in 2% the errors were large enough to cause a difference in full scale IQ of more than 5 points. PMID- 3350881 TI - Convergences and discrepancies, among mothers' and professionals' assessments of difficult neonatal behaviour. AB - The idea that difficult newborn behaviour reflects an inborn disposition was tested by comparing measures from different circumstances, occasions and observers. Correlations between researcher measures from separate settings and occasions were statistically significant but modest, indicating a "rudimentary" constitutional trait contribution to difficult newborn behaviour. Little evidence of a discrete subgroup of particularly difficult newborns was obtained. Maternal assessments were internally consistent but weakly explained by baby constitutional factors or nurses' reports. The importance of contextual and development variables is discussed. Alternative methodological strategies for studying constitutional and social-developmental contributions to difficult behaviour are needed. PMID- 3350882 TI - Blood lead, intelligence, reading attainment, and behaviour in eleven year old children in Dunedin, New Zealand. AB - A study of blood lead levels and intelligence, reading, and behaviour problems was carried out using a sample of 579 Dunedin 11-yr-old children. The results suggested that when account was taken of social, environmental, and background factors, raised blood lead is associated with a small but statistically significant increase in children's general behaviour problems as reported by both parents and teachers. These results applied especially to the more specific problems of inattention and hyperactivity. PMID- 3350883 TI - The relationship between attention problems in childhood and antisocial behavior eight years later. AB - Danish longitudinal population data indicated there was a significant, though weak, relationship between teacher ratings of attention problems in males at ages 10-13 and their cumulative arrest frequency eight years later. However, the child's IQ and maternal reports of his father's problems controlling alcohol intake moderated this relationship; once the variance in antisocial behavior due to these factors was removed, childhood attention problems did not account for any additional variance. These results raise the concern that previous findings of a relationship between clinically diagnosed attention deficit disorder hyperactivity and later delinquency may be due in part to one or more third variables. PMID- 3350884 TI - A twin study of Bannatyne's "genetic dyslexic" subtype. AB - Bannatyne's proposed "genetic dyslexic" subtype of reading disability (RD) was evaluated using data obtained from 60 (30 monozygotic and 30 dizygotic) pairs of affected twins (in which at least one member of each pair has a reading disorder) and 60 pairs of control twins. The predicted spatial greater than conceptual greater than sequential pattern of means was found to be reliable and specific to the RD sample. While this study does not provide conclusive evidence on the genetic etiology of the proposed subtype, our results do indicate that individuals with this particular profile may constitute a specific subtype of reading disability. PMID- 3350886 TI - Psychiatric adjustment in children with chronic renal failure. AB - Problems in psychiatric adjustment were found to be more common in children and adolescents with chronic renal failure (22 subjects on hospital haemodialysis and 22 with less severe renal failure) than in healthy matched controls. There was a trend towards more definite and marked psychological difficulties in patients with more severe renal condition. However, the less severely physically ill children tended to have increased difficulties in school adjustment and they reported more feelings of loneliness. The findings have implications on the management of children with chronic renal failure. PMID- 3350885 TI - Intrapersonal and interpersonal discrepancy among delinquent and nondelinquent girls: a research note. AB - Delinquent and nondelinquent girls were compared to examine the relationship between delinquency and masculine self-concept. Ratings of self and ideal self were obtained to compute self-ideal discrepancy indices on (a) stereotypically sex-related traits and (b) traits which each subject selected as salient to making interpersonal judgements of women. Ratings were also made of best friend and mother to examine interpersonal as well as intra-personal discrepancy indices. For stereotypic sex-role traits, discrepancy indices for the three comparisons (self-ideal, self-mother, self-best friend) revealed no differences between delinquents and nondelinquents. For personally selected traits, significant differences did appear for self-mother and self-best friend discrepancies. PMID- 3350888 TI - Separation and quantitative analysis of some carotenoid fatty acid esters of fruits by liquid chromatography. AB - The adsorption and partition properties of several fatty acid esters of capsanthin, capsorubin, beta-cryptoxanthin, lutein, violaxanthin and beta citraurin isolated from fruits were studied by normal-phase (silica) and reversed phase (octadecylsilane) liquid chromatography using Sudan 1 as internal standard. The separation on a normal phase was based on the functional group of the carotenoids and individual esters of the same carotenoid did not resolve. The separation on a reversed phase was more dependent on the number of acyl carbons than the functional group, and individual esters of the same carotenoid differing only two acyl carbons were separated with a resolution of 3. There was a linear relationship between number of acyl carbons and retention times of the same carotenoid on reversed phase. The separation on a normal phase was the reverse of that on a reversed phase, and a combination of normal-phase followed by reversed phase chromatography was used for the separation of esters with the same or close retention times. PMID- 3350887 TI - Effects of cartoons on emotionally disturbed children's social behavior in school settings. AB - Four classes of emotionally disturbed (ED) children (20 boys and 6 girls, age: M = 8.1 yr) were exposed to six aggressive and six control cartoons. Treatment effects were assessed using direct observations of five categories of behavior during lunch and recess for baseline and the two cartoon conditions. The results revealed significantly more nonphysical aggression following the control cartoons than during baseline across setting and more physical aggression following the control cartoons relative to the aggressive cartoon and baseline conditions in the recess setting. The findings are discussed with regard to their clinical implications and comparability with other field experiments. PMID- 3350889 TI - Quantitative analysis of triglycerides by high-performance liquid chromatography using non-linear gradient elution and flame ionization detection. AB - A high-performance liquid chromatographic (HPLC) technique using a commercial flame ionization detector for the analysis of triglyceride mixtures is described and discussed. A non-linear gradient elution programme giving a linear relationship between equivalent carbon numbers (ECNs) and retention times was developed. A new effect of chain length asymmetry on ECN values has been found. PMID- 3350890 TI - Separations of flavonoids and alkaloids in medicinal herbs by high-speed counter current chromatography. AB - Counter-current chromatography is a new liquid-liquid partition chromatography without using solid support. Recently, the technique has been remarkably improved in both partition efficiency and separation time. In this paper the capability of this high-speed counter-current chromatography was demonstrated on separation of two sets of samples obtained from medicinal herbs: a synthetic mixture of 3' hydroxygenkwanin, luteolin and apigenin was separated on a two-phase solvent system composed of chloroform-methanol-water (4:3:2, v/v/v) and a crude ethanol extract from Anisodus tangulicus (Maxin) Pasch on chloroform-0.07 M sodium phosphate (pH 6.4) (1:1, v/v). In the light of chromatograms obtained from these samples, advantages of high-speed counter-current chromatography over other chromatographic methods were discussed in terms of partition efficiency, peak resolution, separation time, sample loading capacity, etc. PMID- 3350891 TI - Selective purification of cardiac myosin by a high-performance salicylate affinity column. AB - The cardiac muscle proteins, myosin and actin, were purified in one step using a salicylate-silica affinity column. The affinity columns were prepared by coupling sodium salicylate via its hydroxyl group to an Altex Ultraffinity-EP column. Crude detergent extracts from guinea pig hearts were passed through the column and the myosin-actin complex was then eluted with excess free salicylate or high salt. The affinity of cardiac myosin for immobilized salicylate was unique as myosin heavy chain from guinea pig leg muscle detergent extracts could not be purified by this procedure. Commercially purified rabbit leg muscle myosin also appeared to have no interaction with the salicylate affinity column, suggesting that the column is specific for cardiac myosin. PMID- 3350892 TI - Liquid chromatographic method for the determination of bambuterol hydrochloride and related compounds. PMID- 3350893 TI - A biochromatographic technique for the quantitative estimation of triphenyltin fungicides. PMID- 3350894 TI - Improved resolution of enantiomers of naproxen by the simultaneous use of a chiral stationary phase and a chiral additive in the mobile phase. PMID- 3350895 TI - Quantitation of aflatoxins from various strains of aspergillus in foodstuffs. PMID- 3350896 TI - Application of droplet counter-current chromatography to the isolation of vitamin B12. PMID- 3350897 TI - Improved standardization in reversed-phase high-performance liquid chromatography using 1-nitroalkanes as a retention index scale. AB - A retention index scale based on 1-nitroalkanes was introduced for reversed-phase high-performance liquid chromatography. The retention behaviour of nitroalkanes was examined using two different ODS-silica columns. The nitroalkanes are stable compounds having high UV absorbances at 200-220 nm. The correlation between the logarithm of the capacity factor and the carbon number was linear from the second homologue. The compounds up to 1-nitrohexane are easily available commercially, and they cover the retention range for the majority of toxicologically relevant substances. The retention indices of several test compounds showed that the scale based on 1-nitroalkanes is comparable to that based on alkyl aryl ketones, and additionally may cover the early eluted compounds, for which reference compounds on the alkyl aryl ketone scale are not available. PMID- 3350898 TI - Supercritical fluid extraction coupled with supercritical fluid chromatography for the separation of sulfonylurea herbicides and their metabolites from complex matrices. AB - Supercritical fluid chromatography and supercritical fluid extraction have been coupled to provide on-line evaluation of a dynamic extraction procedure. The simultaneous removal and analysis of representative sulfonylureas, their precursors and metabolites from complex matrices was accomplished with this configuration. The matrices examined include soil, plant materials and a cell culture medium. The simplicity and current applicability of this design to the agricultural products industry is demonstrated. PMID- 3350899 TI - Determination of dodecylbenzenesulphonates and ethoxylated alkylphenols in liquid pesticide formulations by high-performance liquid chromatography. AB - A method is presented for determining mixtures of calcium dodecylbenzene sulphonate (CaDBS) and ethoxylated alkylphenols in pesticidal emulsifiable concentrates. The pesticide formulations are adsorbed on a pre-concentration column. The active ingredients, the solvents and the emulsifiers are eluted successively by using solvents with increasing polarities. The various homologues of CaDBS and the ethoxylated alkylphenols are separated by reversed-phase high performance liquid chromatography using methanol-water containing tetramethylammonium bromide. The oligomers of the ethoxylated phenols are separated on an aminopropyl-modified column using a solvent gradient (propan-2-ol water and hexane-tetrahydrofuran). Quantitative results are given for synthetic samples. The degree of ethoxylation of the ethoxylated alkylphenols has been determined and the CaDBS components characterized. PMID- 3350900 TI - Determination of diastereoisomers of bromadiolone, an anticoagulant rodenticide, in animal tissues by high-performance liquid chromatography. AB - Two components isolated by semi-preparative normal phase high-performance liquid chromatography (HPLC) of bromadiolone reference material were tentatively identified as diastereoisomeric forms. Examination by mass spectroscopy confirmed this identification and supporting evidence was provided by identical UV fluorescence characteristics. The separated isomers were used to examine the chromatographic properties of bromadiolone in ion-pair, ion-suppression and weak ion-exchange HPLC modes. Conditions suitable for the analytical determination of the individual diastereoisomers were established for each mode. The influence of mobile phase pH on the resolution of coumarin-based rodenticides by weak ion exchange HPLC on an aminopropyl-bonded phase was studied. Clean-up techniques for the determination of residues of bromadiolone in animal tissue extracts were compared. A combined gel permeation and adsorption chromatographic procedure was preferred for sensitive assay; it permitted the use of either fluorescence or UV detection. The lower practical limit of determination of each isomer in animal tissues was 0.005 mg kg-1 using UV detection and 0.0005 mg kg-1 using fluorescence detection. PMID- 3350901 TI - Monitoring of veterinary drug residues by a combination of continuous flow techniques and column-switching high-performance liquid chromatography. I. Sulphonamides in egg, meat and milk using post-column derivatization with dimethylaminobenzaldehyde. AB - By using a combination of a low-pressure continuous flow module and a column switching high-performance liquid chromatographic system, procedures have been developed for the automated residue analysis of sulphonamides and selected other drugs in meat, egg and milk. Aqueous extracts are purified by on-line dialysis and subsequent trace enrichment on a short column containing silica-based or polymer material. After backflush to the analytical column, detection is performed either at 280 nm or, after post-column derivatization with p dimethylaminobenzaldehyde, at 450 nm. With these procedures the fully automated determination of both polar and apolar sulphonamides and dapsone above 5-20 micrograms/kg is possible. Coefficients of variation are 4-10%, recoveries compared to standards are 85-90%. The methods developed were tested in routine veterinary drug control. PMID- 3350902 TI - The effect of column age on system suitability parameters for an HPLC assay of bitolterol mesylate aerosols. AB - A reversed-phase ion-pairing HPLC method is developed for bitolterol mesylate (Tornalate, Winthrop-Breon) in aerosol dosage forms. Using data acquired by this method during a two-year period, the effect of ODS-3 column age on system suitability parameters is assessed. A BASIC program is used to calculate the resolution factor between bitolterol and colterol triester, capacity factors, number of theoretical plates, and tailing factors in studies that followed the performance of one column during this time period and five columns of different ages under normal usage. A 15 to 30% reduction in column performance per year is found. PMID- 3350903 TI - The use of filter hybridization techniques for the identification, differentiation and classification of plant viruses. AB - In attempts to use dot-blot hybridization tests for the identification of viruses or for assigning them to a certain taxonomic group we found that hybridization signals may be given not only by the homologous virus, but also by heterologous viruses belonging to the same or different taxonomic groups. Possible reasons for this phenomenon, which was observed with uncloned as well as with cloned cDNAs, are discussed. Quantitative dot-blot hybridization tests with extracted viral RNAs proved to be very sensitive in differentiating closely related viruses which were barely distinguishable in serological tests. Estimates on the degree of homology between the RNAs of different viruses may be influenced by a number of experimental parameters, such as competition for the available cDNA between homologous and heterologous RNAs or homologous RNAs in different concentrations on the same sheet of nitrocellulose, saturation phenomena due to close packaging of highly concentrated RNA on the blot and, of course, stringency conditions during washing procedures. Taking these parameters into account we have reestimated the degree of homology between the RNAs of 5 tombusviruses. Our new data suggest that the order of sequence for the relationships among these 5 tombusviruses is similar to that proposed by Koenig and Gibbs (1986) on the basis of serological data. PMID- 3350904 TI - Quantitation of rubella virus by competitive enzyme immunosorbent assay. AB - A simple and rapid technique for quantification of rubella virus is described. The specificity of the competitive enzyme linked immunosorbent assay (ELISA) was quantified by comparing the slopes and the Y intercepts of the curves obtained when viral antigen vs. control antigen was used. The curves were derived by plotting the absorbance ratio against the logarithm of the antigen concentration. The technique was reproducible, its sensitivity depending on the purity of the antigen used. In ELISA, when an antigen precipitated by ammonium sulfate was used, the sensitivity expressed in protein/ml was 7 micrograms and when an antigen purified by sucrose gradient was used, 70 ng, whereas the limit of sensitivity in the standard technique of hemagglutination was only 38 micrograms. PMID- 3350905 TI - Recovery of parathyroid hormone secretion after parathyroid adenomectomy. AB - Using a sensitive two-site immunoradiometric assay which detects only intact human PTH-(1-84), we studied the kinetics of PTH secretion in 19 patients undergoing unilateral neck exploration and removal of a parathyroid adenoma. Preoperative serum PTH values averaged 116 ng/L (normal, 12-65 ng/L). In 8 patients in whom intraoperative sampling was performed, clearance of PTH-(1-84) was rapid, with virtual disappearance of PTH by 120 min after clamping the vascular pedicle to the adenoma. Analysis of the rate of disappearance of PTH-(1 84) indicated an exponential decay with a half-life of 21 min. Thirteen of 19 patients had serum PTH values less than 1 ng/L within 8 h after parathyroidectomy. Recovery of PTH secretion from the suppressed nonsurgically manipulated parathyroid tissue occurred during the nadir of postoperative hypocalcemia. Serum PTH was greater than 10 ng/L in 16 of 19 patients 30 h after removal of the PTH adenoma. Therefore, the functional recovery of atrophic parathyroid tissue is more rapid than that of other endocrine tissues studied to date. PMID- 3350906 TI - Transdermal testosterone therapy in the treatment of male hypogonadism. AB - Five hypogonadal men were treated with transdermal testosterone therapy, using a testosterone patch applied to the scrotal skin. Daily application of the patch, which contained 10 mg testosterone, produced an increase in serum testosterone concentrations from a pretreatment value of 45 +/- 12 (+/- SE; 1.5 +/- 0.4) to 436 +/- 80 ng/dL (15.1 +/- 2.8 nmol/L; P less than 0.001) after 4 weeks of treatment. Normal serum testosterone concentrations were achieved in all men after 6-8 weeks of therapy and were maintained during continued long term therapy for 9-12 months with a patch containing 15 mg testosterone. All men reported a subjective increase in libido and sexual function during therapy, and three men preferred it to testosterone injections. The serum testosterone and estradiol levels did not rise above the normal adult male range at any time during therapy. However, elevated serum dihydrotestosterone (DHT) concentrations occurred during treatment; the pretreatment DHT concentration was 95 +/- 3 ng/dL (3.3 +/- 0.1 nmol/L), and it increased to 228 +/- 40 ng/dL (7.8 +/- 1.4 nmol/L) after 4 weeks of treatment and remained elevated thereafter. The individual mean DHT to testosterone ratio increased from a pretreatment value of 0.2 (range, 0.1-0.3) to 0.6 (range, 0.4-0.7) after 2 weeks of therapy and remained high thereafter. Comparison of the serum DHT levels in patients during therapy with those in normal men who had similar testosterone concentrations [531 +/- 62 vs. 566 +/- 72 ng/dL (18.4 +/- 2.1 vs. 19.6 +/- 2.5 nmol/L); P greater than 0.05] revealed that the mean serum DHT concentration was significantly higher in the patients [315 +/ 69 vs. 87 +/- 6 ng/dL (10.8 +/- 2.4 vs. 2.9 +/- 0.2 nmol/L); P less than 0.001], as was the mean DHT to testosterone ratio [0.6 (range, 0.25- 1.1) vs. 0.16 (range, 0.09- 0.24); P less than 0.001]. The high serum DHT levels presumably were due to increased metabolism of testosterone to DHT by the 5 alpha-reductase in the scrotal skin. Serum 3 alpha-androstanediol glucuronide levels were not elevated in the patients. We conclude that transdermal testosterone therapy is an effective long term treatment for hypogonadism in men. It is, however, associated with high serum DHT levels, whose potential long term effects on the prostate and other tissues need to be investigated. PMID- 3350907 TI - Resistance to insulin-stimulated-glucose uptake in patients with hypertension. AB - Plasma glucose and insulin responses to a glucose challenge and insulin stimulated glucose uptake were measured in 24 age-, weight-, and sex-matched Chinese men (8 with normal blood pressure, 8 with untreated hypertension, and 8 patients with hypertension treated with thiazide and beta-adrenergic antagonist drugs). Plasma glucose and insulin responses were determined by measuring plasma glucose and insulin concentrations before and at 30-min intervals for 2 h after a 75-g oral glucose dose. Insulin-stimulated glucose uptake was estimated by measuring the steady state plasma glucose (SSPG) and insulin (SSPI) concentrations achieved during the last 60 min of a 180-min continuous infusion of somatostatin, insulin, and glucose (insulin suppression test). Under these conditions endogenous insulin secretion was suppressed, and similar SSPI concentrations were achieved in all men; thus, the differences in the resultant SSPG concentrations allowed direct comparison of insulin's ability to stimulate disposal of an identical glucose load in different individuals. The results indicated that the men with hypertension, whether treated or untreated, had significantly elevated plasma glucose (P less than 0.001) and insulin (P less than 0.001) responses to the oral glucose dose compared to the normal men. Mean (+/- SE) SSPG concentrations were also higher (P less than 0.001) in the men with either untreated hypertension [219 +/- 9 mg/dL (12.2 +/- 0.5 mmol/L)] or treated hypertension [211 +/- 18 mg/dL (11.7 +/- 1.0 mmol/L)] than in the normal men [134 +/- 13 mg/dL (7.4 +/- 0.7 mmol/L)]. Since the mean SSPI concentrations were similar in the 3 groups [approximately 70 microU/mL (502 pmol/L)], insulin was less effective in promoting glucose disposal in both groups with hypertension. These results document the fact that patients with hypertension, whether treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic compared to a well-matched control group. PMID- 3350908 TI - Effects of estradiol and progesterone on parathyroid hormone secretion from human parathyroid tissue. AB - Estrogens have been used to treat the hypercalcemia in primary hyperparathyroidism. Estrogens and progesterone both stimulate PTH secretion from bovine parathyroid tissue. The effects of these agents on PTH secretion from human parathyroid tissue are not known. In this study, we evaluated the effects of 17 beta-estradiol and progesterone on PTH secretion from abnormal parathyroid tissue from seven patients (four adenomas, three hyperplasia). Both estradiol (10(-9)-10(-6) mol/L) and progesterone (10(-7) and 10(-6) mol/L) significantly stimulated PTH secretion in a time- and dose-dependent manner during a 3-h period. These results indicate the need for a careful evaluation of serum PTH levels and other parameters of parathyroid function in estrogen- and/or progesterone-treated patients with primary hyperparathyroidism. PMID- 3350909 TI - Hereditary and environmental influences on the variation of thyroid hormones in normal male twins. AB - Heritability of the variation of the plasma total and unbound T4 (free T4), T3, T4-binding globulin (TBG), and TSH concentrations was investigated in 15 monozygotic and 15 dizygotic male twin pairs. The variability in plasma of total (58%) and free T4 (72%) concentrations was significantly less (P less than 0.01) in the twin pairs than in unrelated men. Half of the variability of T3 (P less than 0.05), TBG (P less than 0.05), and TSH (P less than 0.05) was affected by influences shared by the twin pairs in both monozygotic and dizygotic twin pairs. The heritability index for variability of the plasma total T4 and free T4 was greater than 28% (P less than 0.05), and it was 25% or less for T3 and TBG. Variation in TBG accounted for less than 20% (P less than 0.001) of the variation in thyroid hormone concentrations. The results indicate that familial factors, which are affected by genetic and/or environmental factors, influence the variation of plasma TBG, TSH, T4, free T4, and T3 concentrations among normal men. Genetic factors influenced the variation in plasma T4 and free T4 levels. PMID- 3350910 TI - Effect of mouth rinsing with two polyvinylpyrrolidone-iodine mixtures on iodine absorption and thyroid function. AB - A prospective study was conducted to investigate the effect of long term therapy with two iodine-containing mouth rinses on thyroid function. Two groups of subjects were treated daily for 6 months with either a 5% polyvinylpyrrolidone (PVPI)-1.5% H2O2 mixture (Perimed) or a 5% PVPI-water mixture. Thyroid function studies, serum iodine concentrations, and urinary iodine excretion were measured before treatment, at 6-week intervals during the 6-month treatment period, and 3 weeks after the last treatment. There was evidence of significant iodine absorption (elevated serum total iodine and inorganic iodide concentrations and urinary iodine excretion) from daily use of both Perimed and the PVPI-water mixture. Serum T3 and T4 concentrations and the free T4 index did not change. There was a small significant rise in serum TSH concentrations during mouth rinse therapy, but all values remained within the normal range. This small increase in serum TSH is a normal adaptive response to the antithyroid effect of increased iodine intake and accounts for the maintenance of normal serum T4 and T3 concentrations. While daily use of these iodine-containing mouth rinses does result in significant iodine absorption, there is no evidence for the development of thyroid dysfunction during a 6-month course of therapy. PMID- 3350911 TI - Cosecretion of calcitonin gene products: studies with a C18 cartridge extraction method for human plasma PDN-21 (katacalcin). AB - PDN-21, the carboxyl-terminal flanking peptide encoded by the calcitonin (CT) gene, has been found in plasma of patients with medullary thyroid carcinoma and reportedly is cosecreted with CT. To test whether PDN-21 and CT are cosecreted in normal subjects, we developed a RIA for PDN-21 and measured immunoreactive CT and PDN-21 in whole plasma and silica or C18 cartridge extracts of plasma (exCT, exPDN-21) before and after calcium (Ca) infusion (2 mg Ca/kg over 5 min) in nine normal men and nine normal women. Plasma CT and immunoreactive PDN-21 levels were often below the assay detection limits. In contrast, basal exCT and exPDN-21 were detectable in all plasma samples, and the concentrations of both were significantly higher in men than in women [basal exCT (mean +/- SE): men, 4.8 +/- 0.3 ng/L; women, 2.4 +/- 0.3 (P less than 0.001); basal exPDN-21: men, 4.7 +/- 0.3 ng/L; women, 3.3 +/- 0.3 (P less than 0.01)]. Ca infusion sharply increased CT and PDN-21 concentrations in both sexes, but the increments were greatest in men [mean (+/-SE) increment of exCT: men, 37.2 +/- 3.9 ng/L; women, 15.7 +/- 4.3 (P less than 0.002); mean increment of exPDN-21: men, 29.7 +/- 4.7 ng/L; women, 11.0 +/- 3.1 (P less than 0.005)]. The molar concentrations of exCT and exPDN-21 were closely correlated (r = 0.97; P less than 0.001). With our antiserum, the extraction-concentration technique for measurement of PDN-21 had increased sensitivity and decreased nonspecific interference compared to the whole plasma assay. We conclude that CT and PDN-21 are cosecreted from normal thyroid C-cells under the control of extracellular fluid Ca, and that men have greater secretory capacity for both peptides than women. Plasma PDN-21 may serve alternatively to CT as a marker for C-cell activity. PMID- 3350912 TI - Alterations in nocturnal serum melatonin levels in humans with growth and aging. AB - The available data on potential alterations in serum melatonin (MLT) levels during a human lifetime are fragmentary and inconsistent. We, therefore, measured day- and nighttime serum MLT concentrations in 367 subjects (210 males and 157 females), aged 3 days to 90 yr. Blood samples were collected between 0730 and 1000 h and between 2300 and 0100 h. Serum MLT levels were measured by RIA. The mean nighttime serum MLT concentration was low during the first 6 months of life, i.e. 27.3 +/- 5.4 (+/- SE) pg/mL (0.12 +/- 0.02 nmol/L). It then increased to a peak value at 1-3 yr of age [329.5 +/- 42.0 pg/mL; (1.43 +/- 0.18 nmol/L)], and it was considerably lower [62.5 +/- 9.0 pg/mL; (0.27 +/- 0.04 nmol/L)] in individuals aged 15-20 yr. During the following decades serum MLT declined moderately until old age (70-90 yr of age), i.e. 29.2 +/- 6.1 pg/mL (0.13 +/- 0.03 nmol/L). This biphasic MLT decline follows 2 exponential functions with different slopes (from age 1-20 yr: r = -0.56; P less than 0.001; y = 278.7 X e 0.09x; from age 20-90 yr: r = -0.44; P less than 0.001; y = 84.8 X e -0.017x). The decrease in nocturnal serum MLT in children and adolescents (1-20 yr) correlated with the increase in body weight (r = -0.54; P less than 0.001) and body surface area (r = -0.71; P less than 0.001). At a later age (20-90 yr) there was no correlation among these variables. Daytime serum MLT levels were low and no age-related alterations were found. This study revealed major age-related alterations in nocturnal serum MLT levels. The negative correlation between serum MLT and body weight in childhood and adolescence is evidence that expansion of body size is responsible for the huge MLT decrease during that period. The moderate decline at older ages must derive from other factors. PMID- 3350913 TI - Williams syndrome: a neuropsychological profile. AB - Seven children with Williams syndrome were seen for neuropsychological assessment. Their performances were compared with those obtained from a clinical control group matched for age, sex, and Peabody Picture Vocabulary Test Standard Score. The results support the view that children with Williams syndrome suffer from a severe impairment in visual-motor integration. No child in the Experimental Group outperformed his/her matched control on either subtest assessing visual-motor integration skills, while no significant differences were noted between the groups on tests for simple motor skills (e.g., finger oscillation). Significant differences were also found on the subtests of the Wide Range Achievement Test. No significant differences between the groups were noted on tests for general language skills. The remedial educational, and neuropsychological implications of these findings are discussed. PMID- 3350914 TI - Association between familial sinistrality and pathological left-handedness: a comparison of mentally retarded and nonretarded subjects. AB - The hypothesis that familial sinistrality (FS) might be a useful variable for differentiating between pathological and natural left-handers was explored. A comparison of the incidence of FS in mentally retarded and nonretarded samples indicated that a positive history of familial sinistrality (FS+) was significantly more likely to occur in mildly retarded individuals. In addition, left-handed retarded people, in general, were significantly more likely to be FS+ than were right-handed retarded people. PMID- 3350915 TI - Cerebral organization of verbal and motor functions in left-handed and right handed adults: effects of concurrent verbal tasks on unimanual tapping performance. AB - Two experiments were conducted to study the interference effects of different concurrent verbal tasks on unimanual single-finger tapping and unimanual sequential finger tapping. Experiment 1 involved 24 right-handed university students. In the dual-task conditions, right-handers showed a greater right-hand than left-hand performance reduction for single-finger tapping, and an equal right-hand and left-hand reduction for sequential tapping. Experiment 2 involved 60 left-handed university students, divided into four groups according to familial sinistrality and writing hand posture. In the dual-task conditions, left handers showed a greater left-hand than right-hand performance reduction for single-finger tapping, and an equal left-hand and right-hand reduction for sequential finger tapping. A dichotic listening task revealed a left hemispheric dominance for auditory linguistic functioning in most of the left-handers. Familial sinistrality and hand posture, on the whole, did not influence tapping performances. However, these factors influenced the ear asymmetries on the dichotic listening task. It is speculated that, with single-finger tapping, interference only takes place beyond the point of language motor programming, that is to say, at the motor areas and the supplementary motor areas of the cortex. PMID- 3350917 TI - Hand preference and proficiency and cerebral speech dominance determined by the carotid amytal test. AB - Epileptic patients whose speech dominance had been determined with the carotid amytal test were given tests of hand preference, strength, and dexterity. A Discriminant Function Analysis applied to the data correctly identified the side of speech representation in 89.5% of the sample. PMID- 3350916 TI - Learning in young alcoholics. AB - A group of young male alcoholics with a mean age of 26.7 years performed less well than matched controls on a test of complex maze learning. The relatively short period of time during which these alcoholics had been drinking to excess (M = 5.7 years) suggests that acquired deficits may appear earlier in the drinking history of many alcoholics than has been previously assumed. Data from the maze was analyzed by modelling each individuals' cumulative error scores with a two parameter hyperbolic function. The model provided an excellent fit to individual data and group differences were observed in both parameters of the model. It is concluded that curve fitting provides an efficient method for representing individual performance on a multitrial learning task. PMID- 3350918 TI - Reliability and construct validity of the six-block Tactual Performance Test in and adult sample. AB - The ten-block Tactual Performance Test (TPT-10) has been criticized as a clinical instrument due to the long administration time and accompanying psychological distress. The shorter children's six-block version (TPT-6) has been proposed as a potential substitute. The current study examined the internal consistency, the test/retest reliability and the construct validity of the TPT-6. The results indicate that the TPT-6 is a very reliable instrument and is similar to the TPT 10 in terms of construct validity. Most importantly, the actual administration time is approximately one third that of the TPT-10. PMID- 3350919 TI - Recognition memory for words and event-related potentials: a comparison of normal and disabled readers. AB - Visual event-related potentials elicited during a word-recognition memory task were examined for groups of normal and disabled readers (RD). The strong association of reading ability with recognition memory performance endorsed the appropriateness of this signal detection paradigm as a reading-related task. Enhanced amplitude of the P200 component for the RD group was evident during both the acquisition and recognition series and it is indicative of differences at an early sensory stage of item encoding and retrieval. Normal readers displayed greater N400 amplitude than the RD group during both the acquisition and recognition series, an effect which is consistent with more extensive semantic evaluation or memory search that is attributed to that component. In the absence of any remarkable differences in P300 amplitude between groups, the poorer recognition memory performance for the RD group may not be attributable to attentional deficits. PMID- 3350920 TI - Neuropsychological findings in high-functioning men with infantile autism, residual state. AB - Ten men (ages 18-39) with clear histories of Infantile autism and approximately average verbal and nonverbal intelligence were studied with a comprehensive battery of neuropsychological tests. Comparisons with 10 matched normal controls showed no significant differences in many visuoperceptual or memory skills or in sensory-perceptual or motor skills or their lateralization. Differences seen on language measures were small, but statistically significant. In contrast to this, the autistic group demonstrated dramatic deficits on simple and complex, verbal and nonverbal problem-solving tasks, such as the Wisconsin Card Sorting Test, selected tasks from the Stanford-Binet, and the Trail Making Test. A left hemisphere hypothesis of autism was not supported, nor was there compelling evidence of any posterior cortical deficit. Results are compatible with frontal system dysfunction or with more widespread pathology. PMID- 3350921 TI - Visual event perception in alcoholics. AB - A series of microcomputer-based procedures were devised to investigate the ability of alcoholics to detect and locate rapid visual changes, and to assess deficits of visual processing in this patient population. Forty alcoholics were tested 7-13 days after cessation of drinking (mean period of abstinence = 9.5 days), and 24 were retested 2-3 weeks later (mean abstinence = 27.8 days). In comparison to a matched control group the alcoholics were impaired on initial testing at locating visual events. Alcoholics also had significantly slower movement times in a visual-choice reaction time task, and were slower on visual search. At retest the alcoholics were impaired on one of the event perception tasks. Alcoholics were not impaired initially on a measure of visual memory span but were impaired at retest, possibly due to a learning deficit. It is concluded that alcoholics show a persisting deficit in the ability to notice and locate rapid visual changes, together with a transitory impairment on timed tasks requiring visually guided movement. PMID- 3350922 TI - Renorming Russell's version of the Wechsler Memory Scale. AB - Several studies of Russell's version of the Wechsler Memory Scale found that the Logical Memory Scales appeared to be normed too high, indicating a need for renorming. This study produces such a renorming by developing new scale scores and age/education corrections. The scaling used a new method, "reference scale norming". The z scores for 12 tests in the Rennick version of the Halstead-Reitan Battery were averaged and used to establish a reference scale. Scale scores for the memory tests were derived from this scale. The results of this study demonstrated that the earlier Logical Memory Scale norms were in fact too high; this error is corrected. PMID- 3350923 TI - Prognostic significance of anosmia in patients with closed-head trauma. AB - Among 40 patients who developed total anosmia as a result of closed-head injury, virtually all had major vocational problems during the two or more years after being medically cleared to return to work. None had major motor or sensory deficits, and the majority had above average intelligence and memory. However, most demonstrated psychosocial deficits of a type typically associated with damage to orbital frontal cortex. Vocational outcome for patients with partial anosmia was more variable with only about half having manifest vocational problems. PMID- 3350924 TI - Null hypothesis disrespect in neuropsychology: dangers of alpha and beta errors. AB - To understand why there are so many inconsistencies and contradictory findings among hemispheric-asymmetry studies, data were analyzed from a large study of 300 left-handers. These data included information on familial sinistrality (FS), handwriting posture (HPO), a measure of cognitive performance, and five measures of hemispheric specialization. Using computer simulation methodology, 40 independent samples of 36 to 65 subjects each were drawn randomly with replacement. The sample data were analyzed and the results compared to those of the parent "population." Often, the samples poorly reflected the parent "population," and some procedures substantially inflated error rates. These procedures are discussed and specific guidelines suggested. These results are also discussed in the broader context of the necessity for investigators in neuropsychology to differentiate between the statistical and clinical significance of research findings; and to develop a more positive attitude toward the design, execution, and publication of replication studies. PMID- 3350925 TI - Testing to detect brain damage: an alternative to what may no longer be useful. AB - Kane, Parsons, and Goldstein (1985) recently demonstrated that the Halstead Reitan Battery, the Luria-Nebraska Neuropsychological Battery, and the Wechsler Adult Intelligence Scale are all equally effective when used to detect brain damage. This commentary raises the question of whether this type of testing and test development is still useful. Several arguments are made suggesting that it is not. First, it is shown that detecting brain damage alone is usually not clinically useful. Instead, it is argued that neuropsychological instruments more effectively contribute to clinical diagnosis and treatment when used to delineate cognitive function. Additionally, it is demonstrated that brain-damage detection has a number of pitfalls. A method to develop instruments to delineate cognitive function is proposed, and a recent example of such an approach is provided. PMID- 3350926 TI - Papers from the joint meeting of the European Society of Human Reproduction and Embryology and the European Sterility Congress Organization. Budapest, Hungary, September 27-30, 1987. PMID- 3350927 TI - IVF/ET and GIFT in andrology. AB - Improvement in both in-vitro fertilization/embryo transfer (IVF/ET) and gamete intra-Fallopian transfer (GIFT) procedures have led to a progressive extension of their use far beyond the indications represented by tubal problems. One of the most important examples of this is in the field of male infertility. Some researchers claim that IVF/ET is more efficient on the basis of the 'fertilization evidence', while others prefer the GIFT technique, stressing that as its results are clearly so much better that it should be used in all cases. PMID- 3350928 TI - In-vitro fertilization with husband and donor sperm in patients with previous fertilization failures using husband sperm. AB - When previous attempts at in-vitro fertilization using semen from the husband failed, a subsequent IVF attempt was performed using husband and donor sperm in order to compare fertilization and embryo formation after insemination with husband and donor sperm of the same oocyte population. Significantly more eggs were fertilized in patients suffering from andrological and idiopathic infertility when donor sperm were used. No differences were seen in patients with tubal infertility. In the andrological group, the embryos fertilized by the husband showed significantly more fragmentation. No pregnancies were established when husband-fertilized oocytes (embryos) were replaced in the andrological and idiopathic infertility group. This study suggested that an IVF trial using husband and donor sperm might be indicated in couples suffering from andrological or idiopathic infertility in whom no fertilization occurred in a previous cycle using sperm from the husband. PMID- 3350929 TI - Endometriosis and infertility: our experience over five years. AB - During a 5-year period, we diagnosed endometriosis by laparoscopy in 163 infertile patients (7.9% of the infertile population). Seventy-one women presented with minimal endometriosis, 32 women a mild form, 38 women a moderate form and 22 women a severe form. Only 40 patients (24.5%) were found to have endometriosis as the only abnormality in a complete fertility work-up. One hundred and twenty patients were treated with Danazol (600 mg daily for 4-6 months) and 33 of them conceived (27.5%). Twenty-eight patients received conservative surgical treatment associated with Danazol therapy and 11 of them conceived (39.2%). In the 15 patients with minimal endometriosis, who had no therapy but expectant management, there were two conceptions within one year (13.3%). The anticipation of minimal disease in patients with endometriosis as the only abnormality produced about the same results as achieved by active treatment (pregnancy rate of 33.3% after expectant management and 36.3% after treatment). These results suggest that minimal endometriosis can be anticipated only when there are no co-existing factors of infertility. PMID- 3350930 TI - The roles of the individual and organizations in the ethical decision-making process. AB - The roles of various organizations in ethical decision making are considered. Such organizations include local and national ethical committees, professional organizations, religious organizations and governments, and their respective strengths and limitations are discussed in turn. The practising individual scientist or doctor must decide where he or she stands on specific issues, and how he or she will work within the framework established by such organizations. The role of the individual in introducing new concepts or studies under these circumstances is discussed. PMID- 3350931 TI - Early pregnancy factor as a marker for the earliest stages of pregnancy in infertile women. AB - Early pregnancy factor (EPF) is known to be detectable in sera of pregnant women within 24 to 48 h after conception. To examine the incidence of early embryonic loss after hormonal treatment and homologous artificial insemination, we screened the sera of our patients for the presence of EPF by means of a rosette inhibition test. Our results show a considerably lower conception rate as described in appropriate studies on fertile women. If reduced sperm quality is the indication for insemination, the abortion rate in the first 2 weeks of gestation is significantly increased in relation to the rest of our patients. Infertility because of an impaired development of the embryo, especially if repeated EPF positive cycles do not result in a pregnancy, may be due to chromosomal defects or malformations and a chromosomal analysis is recommended. In patients in whom EPF is never found to be positive, indicating a disorder of conception, we regard IVF/ET to be the treatment of choice. PMID- 3350933 TI - Anonymous and non-anonymous oocyte donation preliminary results. AB - During the past year, we have developed an oocyte donation programme in 10 patients with complete absence of endogenous ovarian function (premature ovarian failure in seven cases, castration in two cases and Turner's syndrome in one case). In cases of anonymous donation, donors were volunteers devoid of any major genetical risk who were included in our IVF programme and who consented to donate one oocyte when at least seven oocytes were recovered, and two oocytes when at least 11 oocytes were recovered, to a recipient couple. As far as possible, morphological characteristics of both couples were paired. In cases of non anonymous donation, donors were 'affective' donors, having at least one child. The resulting embryos after IVF of donated oocytes were either replaced directly in recipient women which required synchronization of the donor's and recipient's cycles, or cryopreserved and then thawed, usually at day 16 of recipient's artificial cycle, i.e. 2 days after introduction of the progestational compound. On the 10 patients entering this oocyte donation programme (20 cycles), 13 transfers were carried out resulting in four clinical pregnancies in three patients with premature ovarian failure and one with Turner's syndrome (20% pregnancy per cycle and 31% per transfer). Despite the small numbers, these good results prompted us to develop this protocol. PMID- 3350932 TI - Cryopreservation of human embryos and oocytes. AB - The success rate of human embryo cryopreservation depends on technical and embryonic parameters. First of all, the cryoprotectant can affect embryo survival as we found by comparing two freeze-thaw procedures using propanediol (PROH) (1.5 mol) alone or with sucrose (0.1 mol). Embryo survival was significantly enhanced with sucrose (62 versus 32%). Embryo quality is another major parameter involved in the success of freezing; the rates of positive survival were found to be 67% for morphologically normal embryos versus 49% for embryos with fragments (P less than 0.001). The efficiency of embryo cryopreservation in an IVF programme could be estimated in 1986: a woman with extra embryos, stored after transfer of 3-4 fresh embryos (16% of all cycles), can expect a 22% pregnancy rate per transfer of fresh embryos and a 32% pregnancy rate per collection after transfer of the stored eggs. A comparative study of the cryopreservability of immature or mature oocytes was performed in humans. Human oocytes have a low survival rate (36%) whatever the cryopreservation protocol or the initial maturation stage. Immature human oocytes could survive freezing and thawing, mature and be fertilized in vitro, but with a very low efficiency. PMID- 3350935 TI - The role of cumulus cell-secreted proteins in the development of human sperm fertilizing ability: implication in IVF. AB - Cumulus cells surrounding pre-ovulatory human oocytes were found to secrete a variety of proteins which became firmly associated with the cumulus intercellular material. Antibodies raised against human cumuli oophori completely blocked fertilization in vitro by impairing the sperm-zona pellucida interaction. A group of glycoproteins of high mol. wt were identified as the main cumulus cell secretory products. These proteins showed a marked affinity for human spermatozoa and were potent stimulators of the conversion of human and boar proacrosin into acrosin and of human sperm acrosome reaction. Another fraction of proteins of human cumulus intercellular matrix with an apparent mol. wt of approximately 25,000 daltons was also found to stimulate significantly the acrosome reaction of human spermatozoa, although this fraction had no proacrosin-converting activity. These results indicate that proteins secreted by pre-ovulatory human cumulus cells have an indispensable role in the development of human sperm fertilizing ability. This effect seems to be realized by a concerted action of different types of cumulus-derived proteins just prior to and during the sperm-zona pellucida interaction. Disorders of cumulus cell secretory activity may account for some cases of idiopathic infertility and repeated IVF failures. PMID- 3350934 TI - Chromosome analysis of human oocytes and embryos: does delayed fertilization increase chromosome imbalance? AB - Thirty per cent of a sample of 120 unfertilized human oocytes carried chromosome abnormalities highly correlated with maternal age (38% in patients greater than 35, as compared with 24% in younger patients). Fertilized eggs, when observed 17 h after insemination, showed in 1.6% a single pronucleus suggesting parthenogenetic activation. In 92% of the cases two pronuclei were observed and the rate of chromosome anomalies depended on the morphological aspect of the embryos. Triploidy was also encountered in 6.4% of the eggs leading to an overall rate of chromosome aberrations reaching 29.2%. Delayed fertilization drastically increased the rate of chromosome anomalies (87%) as well as the rate of mosaicism: 30% versus 10.6% in timely fertilized eggs. The high rate of chromosome disorders in early life after in-vitro fertilization (IVF) raises the ethical question of the opportunity of carrying out a genetic control of normality in human embryos at the preimplantation stage. PMID- 3350937 TI - Sperm-cervical mucus interaction, in particular in the presence of antispermatozoal antibodies. AB - Disturbances of the interaction between spermatozoa and cervical mucus can cause subfertility or infertility. The diagnosis of such a disturbed interaction is possible with simple laboratory tests. Oligomucorrhoea and dysmucorrhoea are the most frequent causes of a disturbed sperm--cervical mucus interaction. Antispermatozoal IgA plays a quantitatively limited, but qualitatively important role. Sophisticated time-consuming laboratory investigations have mostly only additional value for the diagnosis. PMID- 3350936 TI - Anti-sperm antibodies and immune subfertility. AB - A brief description of immune subfertility, caused by antibodies directed against sperm-specific glycoproteins in the sperm membrane, is given. Observations during the last few years have indicated that this immune disease is primarily caused by anti-sperm antibodies of the IgA class, and recent results from vasovasostomized men lend further support to this theory. Detection of anti-sperm antibodies should therefore include characterization of the immunoglobulin class of antibodies. In male patients this can be achieved by direct mixed anti-globulin reaction test or immunobead-binding test on the patients' spermatozoa, and in female patients cervical mucus can be tested by indirect versions of the same tests. PMID- 3350938 TI - Promotion of research in human reproduction: global needs and perspectives. AB - The WHO Special Programme of Research, Development and Research Training in Human Reproduction was established in 1972, to respond to a global expansion in research needs in human reproduction, especially in the area of fertility regulation. The Programme's limited resources come from voluntary contributions by governments and international agencies. The emphasis is always on the needs of developing countries. The Programme has to keep the field under continuous review, and to direct its limited resources to the major unmet needs. This paper presents, from a global perspective, the needs and priorities in the promotion of research in human reproduction. It is emphasized that research has to be backed up by political commitment and resources if it is to have an impact on reproductive health. The role of determinants of health, other than and beyond the medical services, has also to be recognized. Promotion of research in human reproduction, to serve developing country needs, has to move into two directions. One is the mobilization of a global effort to develop and test technologies, where the available technologies are not satisfactory to meet the needs and where the research is slackening. The second is the strengthening of in-country resources for research to deal with country-specific problems and to enable countries to utilize, to the best, available technologies. PMID- 3350940 TI - Immunology of early pregnancy. AB - The results of immunization of women with recurrent spontaneous abortion with paternal lymphocytes are described. The women we have treated were those with more than two spontaneous abortions with the same partner, who did not have evidence of genetic or other causes of recurrent abortion. Only women with recurrent abortion and no more than one live child were considered suitable for treatment. The success of treatment before pregnancy was 77%, similar to that found in our original double-blind controlled trial of immunization. The failures of treatment were found to cluster in those women who did not make detectable cytotoxic antibody after treatment, and who did not become pregnant within 90 days. Those women who did develop antipaternal antibody after immunization showed a protective response with no significant drop in efficiency in the year after immunization. A further group of women are described who were treated in the early part of pregnancy. The success rate was very high when the treatment was given within 40 days of the last period, and was less effective the later in pregnancy it was given. Birthweight, gestational age and malformation rate of the babies born after treatment were not different from those found in the normal population. PMID- 3350939 TI - Immunobiology of male infertility. AB - Experimental and clinical data reported in the literature emphasize the important role that immune factors may play in the genesis of male infertility even if many problems still remain to be solved. Auto or homo-sensitization in animals (and in male volunteers) can be obtained with testicular homogenate or epididymal spermatozoa and complete Freund's adjuvant. Immune orchitis in spontaneous human pathology has also been reported. Vasectomy for the voluntary control of male fertility may be considered a particular form of experimental autoimmunization; and many vasectomized individuals develop antisperm antibodies in blood serum and/or in seminal plasma. In spontaneous male infertility antisperm antibodies can: (i) be a mere epiphenomenon; (ii) be a factor aggravating a pathologic situation already able to cause infertility; (iii) play a pathogenetic role in some forms of so-called idiopathic infertility and so could be defined as infertility due to antisperm antibodies. If the antisperm autoimmune reaction represents the casual factor of infertility, corticosteroid therapy seems to give the most satisfactory results, administered either in high doses for a very short time period or in low doses over a prolonged period, or even after transient pharmacologically induced azoospermia. PMID- 3350941 TI - Glass wool column filtration of human semen: relation to swim-up procedure and outcome of IVF. AB - The number and viability of spermatozoa recovered by glass wool column filtration and a swim-up procedure were compared using different types of ejaculates, such as normal, asthenozoospermic and very viscous oligozoospermic semen. The filtration procedure resulted in significantly (P less than 0.01) higher recovery of viable spermatozoa than the swim-up procedure from all types of ejaculates studied. Further, the spermatozoa from 50 (78.1%) of the 64 ejaculates filtered through glass wool column fertilized at least one intact human egg in an in-vitro fertilization (IVF) procedure. It is concluded that glass wool column filtration is superior to the swim-up procedure since it yields a higher recovery of viable spermatozoa that are potentially fertile. Therefore, the glass wool column filtration procedure used to prepare spermatozoa may be of benefit for IVF, intra uterine insemination, in-vitro fertilization and GIFT (gamete intra-Fallopian transfer), especially in cases of poor quality semen. PMID- 3350942 TI - Assessment of sperm function for IVF. AB - Recent advances in our ability to understand and manipulate the fundamental mechanisms regulating human sperm function have led to the development of a new generation of diagnostic techniques, designed to give objective data on the functional competence of human spermatozoa. These techniques have proved to be of value in predicting the ability of patients' spermatozoa to fertilize the human ovum in vitro and in the evaluation of techniques and reagents of relevance to the therapeutic application of IVF, including sperm preparation protocols and reagents for the artificial enhancement of sperm function. Moreover the use of sperm function tests has shed light on the biochemical nature of the lesions present in the spermatozoa of subfertile males, with particular emphasis on the role played by reactive oxygen species. As a result of such studies we are now in a position to adopt a more rational approach to the development of modified IVF protocols for the treatment of male infertility. PMID- 3350943 TI - Intrauterine insemination. AB - Fifty-six couples with infertility due either to subnormal sperm (n = 40), hostile cervical mucus (n = 5) or idiopathic infertility (n = 11), were treated with intrauterine insemination of washed sperm. A total of 78 treatment cycles were completed. Nine pregnancies resulted from these insemination cycles, giving an overall pregnancy rate of 8.3% per treatment cycle. Eight pregnancies occurred in the andrologic group after 56 treatment cycles. One pregnancy was established in the patient group with idiopathic infertility after 15 treatment cycles, while no pregnancy occurred in the patient group with infertility due to cervical mucus hostility. The mean number of years of infertility in the couples conceiving following treatment was 7 years (range 3-11). The spontaneous pregnancy rate in this patient group is low. The data obtained in this study suggest that in selected patients intrauterine insemination will result in an acceptable pregnancy rate. There is a need for a randomized prospective study designed to compare the efficacy of intrauterine insemination with that of alternative treatment modalities. PMID- 3350944 TI - A comparison between spinous process and sublaminar wiring combined with Harrington distraction instrumentation in the management of adolescent idiopathic scoliosis. AB - A study of the efficacy of two techniques of spinal instrumentation on patients with adolescent idiopathic scoliosis was performed. Twenty consecutive patients treated with a single Harrington distraction rod and sublaminar wiring (H-SL) were compared with 20 consecutive patients treated with a single Harrington distraction and spinous process wiring (H-SP). The patients in both groups were similar in age, curve magnitude, curve flexibility, and curve type. The immediate postoperative correction (61% H-SL, 58% H-SP) and follow-up correction (50% H-SL, 49% H-SP) were equivalent. No pseudarthroses were recognized in either group. One patient with H-SL had transient postoperative paresthesias. PMID- 3350945 TI - Pulmonary function and scoliosis in Duchenne dystrophy. AB - Pulmonary function data were evaluated in 68 Duchenne muscular dystrophy patients to determine the rate of decline of the percentage of normal forced vital capacity (FVC). The percentage of normal FVC declined most rapidly during the adolescent growth spurt, which demonstrated a need for an accurate and reliable means for determining height in these patients. The age at 35% of normal FVC was 14.9 +/- 3.6 years (2 SD), and survival for the 28 patients who died was 3.2 (range 0.2-5.7) years. Pulmonary function tests were performed 10-74 months after spinal stabilization on 21 Duchenne dystrophy patients and compared with 46 nonfused scoliotic Duchenne patients. No difference was found in the rate of deterioration of the percentage of normal FVC. PMID- 3350946 TI - Scoliosis in Rett syndrome. AB - Rett syndrome is a progressive encephalopathy observed only in girls, who are apparently normal until 6 to 12 months of age. It is characterized by autism, dementia, ataxia, stereotypic hand movements, hyperreflexia, spasticity, and seizures. Eight of 10 females with Rett syndrome evaluated at the Alfred I. duPont Institute have C-shaped neuromuscular curves averaging 29 degrees (range 22-48 degrees). Curve progression was seen in all eight patients and occurred despite bracing in four, averaging 21 degrees (range 12-31 degrees). Five patients, two of whom were braced, have undergone posterior spinal fusion with segmental instrumentation for curves ranging in size from 49 to 105 degrees (average 67 degrees). PMID- 3350947 TI - Brace-wear compliance in patients with adolescent idiopathic scoliosis. AB - Thirty-eight full-time and 38 part-time unselected brace wearers treated during a 7-year period were interviewed in a retrospective study to determine actual brace wear compliance. Actual compliance was found to be lower than reported by patients during clinic visits and was much lower than reported in previous series. Only 15% of patients were highly compliant. On average, patients wore their braces 65% of the time they were instructed to do so. The reasons for low compliance in brace wear are unclear. PMID- 3350948 TI - Spinal cord injury without osseous spine fracture. AB - Sixteen patients with spinal cord injury without osseous spine fracture and 55 patients with spinal cord injury with osseous spine fracture aged from birth through 18 years were studied. Those without osseous fracture were younger (mean age 6 years) than were those with osseous fracture (mean age 16 years). Extravasation of myelographic dye from the spinal canal was a poor prognostic sign. All three in the group with this finding without osseous fracture had complete spinal cord lesions. Those without osseous fracture should be followed for the development of late spinal deformity that may require orthotic support or surgical stabilization. PMID- 3350949 TI - Differentiation of idiopathic toe-walking and cerebral palsy. AB - Kinematic data were collected on two groups of children with diagnoses of idiopathic toe-walking and mild spastic diplegia. Although both groups lacked a heel strike at initial contact, two distinct gait patterns were found. The toe walkers displayed a variable pattern of ankle motion with moderate to severe plantarflexion at stance. The cerebral palsy patients showed a repeatable gait pattern with only minimal deviation from normal. The absence of a heel strike in this group is due to the sustained knee flexion at terminal swing and initial contact, which was significantly greater than in the toe-walkers. PMID- 3350950 TI - Anterior transfer of the long toe flexors for the treatment of spastic equinovarus and equinus foot in cerebral palsy. AB - Anterior transfer of the long toe flexors combined with the Baker procedure, or heel cord lengthening was used to correct equinus foot deformity in 21 patients with cerebral palsy. In more than two-thirds of the cases, heel-to-ball gait became possible. There were no significant recurrences that required re operation. There were no complications caused by loss of original function in the long toe flexors even in younger patients. Excellent and good results were seen in 57.1% of the patients according to the overall results. PMID- 3350952 TI - Grice subtalar arthrodesis followed to skeletal maturity. AB - A retrospective review of 45 patients (62 feet) who had undergone a Grice subtalar arthrodesis and who had reached skeletal maturity was undertaken. Preoperative deformities were due to flaccid and spastic paralysis, as well as congenital abnormalities. There were failures in 32% and poor results in 61%. Unrecognized ankle valgus, overcorrection of the hindfoot into varus, uncorrected calcaneus deformity, and anterior graft orientation largely contributed to the poor results. Weight-bearing radiographs of the feet and ankles are necessary to distinguish ankle valgus from hindfoot valgus. A subtalar arthrodesis cannot be used to compensate for ankle valgus, nor can it be used to correct the calcaneus component of a deformity without appropriate muscle-balancing procedures or osteotomies. PMID- 3350951 TI - Fibular-Achilles tenodesis for paralytic ankle valgus. AB - Children with myelomeningocele often develop progressive valgus deformity of the ankle that may be concomitant with, or mistaken for, paralytic hindfoot valgus. The same deformity is encountered in children who sustain lower motor neuron deficits. It is imperative to obtain an anteroposterior weight-bearing radiograph of the ankles to differentiate and document the degree of ankle valgus. To address the ankle deformity, we employed the fibular-Achilles tenodesis described by Westin. We are reporting our experience with 18 patients (32 ankles) who underwent this procedure. We noted improvement in relative fibular length and reduced talar tilt in 26 ankles (81.2%). In addition, there was some improvement in the orientation of the hindfoot; rotational deformity was unaffected. PMID- 3350953 TI - Effect of ankle valgus on radiographic appearance of the hindfoot. AB - The integral relationship between the ankle and the hindfoot may compromise the interpretation of weightbearing radiographs of the feet. The ankle should be horizontal if meaningful observations are to be made about hindfoot alignment. This pitfall is demonstrated using an anatomic specimen and several clinical examples. An anteroposterior radiograph of the ankle should be obtained before one contemplates stabilization or realignment of the hindfoot. PMID- 3350954 TI - Late-onset tibia vara: a histopathologic analysis. A comparative evaluation with infantile tibia vara and slipped capital femoral epiphysis. AB - Histopathologic and histochemical studies were performed on the entire physes and contiguous structures of five knees (three patients) with late-onset tibia vara (Blount's disease). A constellation of abnormalities of both medial and lateral physeal components resulted in disorganization and misalignment of the physeal zones. The changes were remarkably similar to those observed in both infantile tibia vara and slipped capital femoral epiphysis, suggesting a common etiology. Our evaluation indicates that asymmetric compressive and shear forces acting across the proximal tibial physis effect its disruption and causes suppression and deviation of normal endochondral ossification, thereby resulting in tibia vara. PMID- 3350955 TI - Maturation factors in slipped capital femoral epiphysis. AB - Several maturation factors relative to growth and epiphyseal development were reviewed retrospectively in 191 patients with slipped capital femoral epiphysis, including bone age, height and weight, thyroid functions, sex hormone levels, and growth hormone levels. Seventy-one percent of 138 patients had weights above the 80th percentile. Active thyroid (T3) was significantly low in 25% of 80 patients studied. Testosterone levels were markedly depressed in 76% of 64 patients tested. In this same group, 87% had low growth hormone levels. The consistently low testosterone and growth hormone levels, along with a tendency toward hypothyroidism, lend support to the biochemical theory of a delicate hormonal imbalance in slipped capital femoral epiphysis. PMID- 3350956 TI - Idiopathic chondrolysis of the hip: management by subtotal capsulectomy and aggressive rehabilitation. AB - Three cases of idiopathic chondrolysis were treated by a subtotal circumferential capsulectomy with follow-up for 3 years and 1 month. Concomitant muscle releases were performed as necessary to relieve joint contractures. Surgery was followed by an aggressive rehabilitation effort. All patients were symptom-free and displayed an extremely satisfactory range of motion. Radiographs revealed reconstitution of the joint space in all cases. We believe that this aggressive management is well justified when one considers the results of previous published reports. PMID- 3350957 TI - Computerized blood flow analysis for decision making in the treatment of osteochondritis dissecans. AB - Patients presenting the radiologic appearance of osteochondritis dissecans (OCD) require a decision as to further treatment. This often requires an invasive procedure. The noninvasive technique of computerized blood flow analysis (CBFA) has been used in 13 patients with OCD. In clinically early disease (four patients), there is always decreased flow in the area distal to the OCD lesion. Patients with intermediate OCD (four patients) showed characteristics of healing reflected in increased flow to the OCD lesion. These patients were left under observation and underwent spontaneous healing. Patients who showed no increase in flow or had decreased flow in the area of involvement (four patients) were clinically found to be nonviable OCD and required surgical intervention. The technique of CBFA therefore holds promise for decision making in the management of this disease. PMID- 3350958 TI - Histiocytosis X with scoliosis and osteolysis. AB - Histiocytosis X can exhibit a variety of musculoskeletal manifestations. Nonetheless, this case exhibits two striking features. Severe progressive scoliosis and massive osteolysis of both femoral shafts occurred in conjunction with the Hand-Schuller-Christian form of histiocytosis X. The scoliosis was treated successfully by posterior fusion and instrumentation. The clinical features of histiocytosis X are reviewed. Speculation as to the etiology of these features is presented. PMID- 3350959 TI - Thick lips, bumpy tongue, and slipped capital femoral epiphysis--a deadly combination. AB - Multiple endocrine neoplasia type 2b (MEN 2b) is a rare genetic disorder. Affected individuals have malignant thyroid tumors, pheochromocytoma, and ganglioneuromatosis. The musculoskeletal manifestations of MEN 2b include a Marfanoid habitus, pes cavus, scoliosis, slipped capital femoral epiphysis, joint laxity, poor muscle development, and delayed maturation. The initial clinical presentation of MEN 2b frequently involves the musculoskeletal system. The characteristics ganglioneuromatosis of the lips and tongue, however, should alert the orthopedic surgeon to the underlying disorder. Effective treatment of the malignant neoplasms hinges on early diagnosis. The risk of perioperative hypertensive crisis is significant; it may be prevented by appropriate treatment of the pheochromocytoma. PMID- 3350960 TI - Epiphyseal separation in scurvy. AB - The case of a 10-month-old boy with scurvy and epiphyseal displacement of both the distal femur and the right proximal tibia is presented. He was treated without reduction of the displacement. PMID- 3350962 TI - Effects of neurodevelopmental treatment on movement patterns of children with cerebral palsy. PMID- 3350961 TI - Congenital dislocation of the knee. PMID- 3350963 TI - Paradoxical glottic narrowing in patients with severe obstructive sleep apnea. AB - Most patients with obstructive sleep apnea have increased pharyngeal collapsibility (defined in the present study as an increased lung volume dependence of pharyngeal area), which predisposes them to upper airway occlusion during sleep. However, there are patients with severe obstructive sleep apnea who have low-normal pharyngeal collapsibility. The factors leading to nocturnal upper airway obstruction in such patients have not been ascertained. We studied 10 overweight male patients with severe obstructive sleep apnea and low-normal pharyngeal collapsibility to determine the site of upper airway pathology in these patients. We found that all 10 patients exhibited paradoxical inspiratory narrowing of the glottis during quiet tidal breathing. This phenomenon was not observed in a matched group of 10 snoring, nonapneic male controls. We conclude that paradoxical glottic narrowing may be a contributing factor in the pathogenesis of upper airway obstruction in patients with severe obstructive sleep apnea who have low-normal pharyngeal collapsibility. PMID- 3350964 TI - Induction of de novo bone formation in the beagle. A novel effect of aluminum. AB - To define the primary effects of aluminum on bone in the mammalian species, we examined the dose/time-dependent actions of aluminum in normal beagles. Administration of low dose aluminum (0.75 mg/kg) significantly elevated the serum aluminum (151.7 +/- 19.9 micrograms/liter) compared with that in controls (4.2 +/ 1.35 micrograms/liter) but did not alter the calcium, creatinine, or parathyroid hormone. After 8 wk of therapy, bone biopsies displayed reduced bone resorption (2.6 +/- 0.63 vs. 4.5 +/- 0.39%) and osteoblast covered bone surfaces (2.02 +/- 0.51 vs. 7.64 +/- 1.86%), which was indicative of low turnover. In contrast, prolonged treatment resulted in increased bone volume and trabecular number (38.9 +/- 1.35 vs. 25.2 +/- 2.56% and 3.56 +/- 0.23 vs. 2.88 +/- 0.11/mm) which was consistent with uncoupled bone formation. Administration of higher doses of aluminum (1.20 mg/kg) increased the serum aluminum further (1242.3 +/- 259.8 micrograms/liter) but did not affect calcium, creatinine, or parathyroid hormone. However, after 8 wk of treatment, bone biopsies displayed changes similar to those after long-term, low-dose therapy. In this regard, an increased trabecular number (3.41 +/- 0.18/mm) and bone volume (36.5 +/- 2.38%) again provided evidence of uncoupled bone formation. In contrast, in this instance poorly mineralized woven bone contributed to the enhanced bone volume. High-dose treatment for 16 wk further enhanced bone volume (50.4 +/- 4.61%) and trabecular number (3.90 +/- 0.5/mm). These observations illustrate that aluminum may stimulate uncoupled bone formation and induce a positive bone balance. This enhancement of bone histogenesis contrasts with the effects of pharmacologic agents that alter the function of existing bone remodeling units. PMID- 3350965 TI - Hematopoietic microenvironment. Origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice. AB - Studies of bone marrow transplant patients have suggested that the stromal cells of the in vitro hematopoietic microenvironment are transplantable into conditioned recipients. Moreover, in patients with myeloproliferative disorders, all of the stromal cells, which include presumptive endothelial cells, appear to be derived from hematopoietic precursors. To confirm these findings, we have constructed two chimeric mouse models: (a) traditional radiation chimeras, and (b) fetal chimeras, produced by placental injection of bone marrow into genetically anemic Wx/Wv fetuses, a technique that essentially precludes engraftment of nonhematopoietic cells. Using two-color indirect immunofluorescence, the stromal cells in long-term bone marrow culture derived from these chimeras were analyzed for donor or host origin by strain-specific H-2 antigens, and for cell lineage by a variety of other specific markers. 75-95% of the stromal cells were shown to be hematopoietic cells of the monocyte-macrophage lineage, based upon donor origin, phagocytosis, and expression of specific hematopoietic surface antigens. The remaining 5-25% of the stromal cells were exclusively host in origin. Apart from occasional fat cells, these cells uniformly expressed collagen type IV, laminin, and a surface antigen associated with endothelial cells. Since these endothelial-like cells are not transplantable into radiation or fetal chimeras, they are not derived from hematopoietic stem cells. The contrast between our findings and human studies suggests either unexpected species differences in the origin of stromal lineages or limitations in the previous methodology used to detect nonhematopoietic stromal cells. PMID- 3350966 TI - Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury. Evidence for direct cellular action of prostaglandin. AB - Isolated human gastric glands from surgical specimens were preincubated in an oxygenated medium with placebo or 16,16 dimethyl prostaglandin E2 (dmPGE2) and incubated at 37 degrees C in either medium alone, medium containing 4.43 mM indomethacin or medium containing 8% ethanol. We assessed the viability of gland cells with fast green exclusion, release of lactate dehydrogenase (LDH) into the medium, and ultrastructural damage by scanning and transmission electron microscopy. Both indomethacin and ethanol significantly reduced the viability of placebo-pretreated glands, increased LDH release into the medium, and produced prominent ultrastructural damage. DmPGE2 significantly reduced both indomethacin and ethanol-induced injury, increased the number of viable cells, reduced LDH release, and diminished the extent of ultrastructural damage. These studies indicate that PG protection of gastric mucosal cells has a direct cellular action that is not limited to replacement of depleted endogenous PGs. PG protection in our experiments did not depend on PG's previously described systemic actions, such as protection of the microvessels, preservation of the mucosal blood flow, or stimulation of bicarbonate and mucus secretion. PMID- 3350968 TI - Electrical and mechanical activity in the human lower esophageal sphincter during diaphragmatic contraction. AB - To determine the effect of contraction of the diaphragm on the lower esophageal sphincter (LES) pressure, we studied eight healthy volunteers during spontaneous breathing, maximal inspiration, and graded inspiratory efforts against a closed airway (Muller's maneuver). Electrical activity of the crural diaphragm (DEMG) was recorded from bipolar esophageal electrodes, transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures, and LES pressure was recorded using a sleeve device. During spontaneous breathing, phasic inspiratory DEMG was accompanied by phasic increases in Pdi and LES pressure. With maximal inspiration, DEMG increased 15-20-fold compared with spontaneous inspiration, and LES pressure rose from an end-expiratory pressure of 21 to 90 mmHg. Similar values were obtained during maximal Muller's maneuvers. LES pressure fell promptly when the diaphragm relaxed. Graded Muller's maneuver resulted in proportional increases in the Pdi, LES pressure, and DEMG. The LES pressure was always greater than Pdi and correlated with it in a linear fashion (P less than 0.001). We conclude that the contraction of the diaphragm exerts a sphincteric action at the LES, and that this effect is an important component of the antireflux barrier. PMID- 3350967 TI - Alterations in cation homeostasis in cultured chick ventricular cells during and after recovery from adenosine triphosphate depletion. AB - Alterations in cation homeostasis during and after recovery from myocardial ischemia may account for some of the reversible and irreversible components of myocardial cell injury. To investigate possible mechanisms involved, we exposed cultured layers of spontaneously contracting chick embryo ventricular cells to media containing 1 mM cyanide (CN) and 20 mM 2-deoxyglucose (2-DG), and zero glucose for up to 6 h, and then allowed cultured cells to recover in serum-free culture medium for 24 h. Changes in Na, K, and Ca contents, 42K uptake and efflux, ATP content, cell water content, and lactate dehydrogenase (LDH) release were measured, and compared with changes produced by exposure to 10(-3) M ouabain and severe hypoxia. Exposure to CN and 2-DG caused marked increase in cell Na (sevenfold) and Ca (fivefold) contents, and a decrease in K content (one-fifth normal), coincident with ATP depletion to one-tenth normal levels. This produced only slight cell injury, evidenced by increased LDH release. Recovery for 24 h resulted in return to near normal values (expressed in nanomoles per milligram of protein) of Na, Ca, and ATP contents. However, there was failure of cell K content to return to normal, associated with a persistent reduced net uptake of 42K, and an increase in the rate of 42K efflux. These abnormalities in K homeostasis were associated with a decrease in cell volume and water content per milligram of protein. More marked ATP depletion (to 1/100 normal values) was produced by hypoxia plus 2-DG and zero glucose, and was associated with much more severe cell injury manifested by LDH loss. Ouabain exposure resulted in a much greater Ca gain (20-30-fold), relative to increase in Na content, than did either CN and 2-DG or hypoxia; and ouabain effects were not reversible (after a 15-fold or greater increase in Ca content was produced) and were associated with significant LDH release. We conclude that these cells are resistant to cell injury caused by moderately severe Ca overload and ATP depletion produced by exposure to CN and 2-DG. However, metabolic inhibition of ATP production produces persistent abnormalities in K homeostasis, associated with functional abnormalities. PMID- 3350970 TI - Perinatal hypophosphatasia: tissue levels of vitamin B6 are unremarkable despite markedly increased circulating concentrations of pyridoxal-5'-phosphate. Evidence for an ectoenzyme role for tissue-nonspecific alkaline phosphatase. AB - "Perinatal" hypophosphatasia is the most severe form of this inborn error of metabolism, which is characterized by deficient activity of the tissue nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP) (TNSALP). We report that autopsy tissue from three affected subjects, which was profoundly low in ALP activity, had essentially unremarkable levels of pyridoxal-5' phosphate (PLP), pyridoxal, and total vitamin B6 content despite markedly elevated plasma PLP levels (5,800, 14,500, and 98,500 nM; adult norm, 5-109 nM). Our findings help to explain the general absence of symptoms of vitamin B6 excess or deficiency in hypophosphatasia, and provide evidence that TNSALP acts as an ectoenzyme to regulate extracellular rather than intracellular concentrations of PLP (the cofactor form of vitamin B6) and perhaps other phosphate compounds. PMID- 3350969 TI - 31P nuclear magnetic resonance studies of high energy phosphates and pH in human muscle fatigue. Comparison of aerobic and anaerobic exercise. AB - The goal of these experiments was to investigate the relationship of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), monobasic phosphate (H2PO4-), and pH to human muscle fatigue. Phosphates and pH were measured in adductor pollicis using 31P nuclear magnetic resonance at 2.0 Tesla. The force of muscle contraction was simultaneously measured with a force transducer. The effects of aerobic and anaerobic exercise were compared using two exercise protocols: 4 min sustained maximal voluntary contraction (MVC) and 40 min of repeated intermittent contractions (75% MVC). The sustained maximal contraction produced a rapid decline of MVC and PCr, and was accompanied by a rapid rise of Pi, H+, and H2PO4 . Intermittent exercise produced steady state changes of MVC, pH, and phosphates. No significant changes of ATP were found in either protocol. During fatiguing exercise, PCr and Pi had a nonlinear relationship with MVC. H+ showed a more linear correlation, while H2PO4- showed the best correlation with MVC. Furthermore, the correlations between MVC and H2PO4- were similar in sustained (r = 0.70) and intermittent (r = 0.73) exercise. The highly significant linear relationship between increases of H+ and H2PO4- and the decline of MVC strongly suggests that both H+ and H2PO4- are important determinants of human muscle fatigue. PMID- 3350971 TI - Reactive oxygen species during ischemia-reflow injury in isolated perfused rat liver. AB - The hypothesis that intracellular generation of reactive oxygen species in hepatocytes or reticuloendothelial cells may cause ischemia-reperfusion injury was tested in isolated perfused livers of male Fischer rats. GSSG was measured in perfusate, bile, and tissue as a sensitive index of oxidative stress. After a preperfusion phase of 30 min, the perfusion was stopped (global ischemia) for various times (30, 120 min) and the liver was reperfused for another 60 min. The bile flow (1.48 +/- 0.17 microliters/min X gram liver weight), the biliary efflux of total glutathione (6.54 +/- 0.94 nmol GSH eq/min X g), and GSSG (1.59 +/- 0.23 nmol GSH eq/min X g) recovered to 69-86% after short-term ischemia and to 36-72% after 2 h of ischemia when compared with values obtained from control livers perfused for the same period of time. During reperfusion, the sinusoidal efflux of total glutathione (16.4 +/- 2.1 nmol GSH eq/min X g) and GSSG (0.13 +/- 0.05 nmol GSH eq/min X g) did not change except for an initial 10-30-s increase during reperfusion washout. No increased GSSG secretion into bile was detectable at any time during reperfusion. The liver content of total glutathione (32.5 +/- 3.5 nmol GSH eq/mg protein) and GSSG (0.27 +/- 0.09 nmol GSH eq/mg protein) did not change significantly during any period of ischemia or reperfusion. We conclude, therefore, that at most only a minor amount of reactive oxygen species were generated during reperfusion. Thus, reactive oxygen species are unlikely to cause ischemia/reperfusion injury in rat liver by lipid peroxidation or tissue thiol oxidation. PMID- 3350972 TI - Mechanisms whereby exogenous adenine nucleotides improve rabbit renal proximal function during and after anoxia. AB - When a suspension of rabbit proximal tubules is subjected to anoxia, ATP falls by 80-90% during 40 min of anoxia, and upon reoxygenation (reox) the cells only recover 25-50% of their initial ATP. Addition of Mg-ATP (magnesium chloride treated ATP), Mg-ADP, or Mg-AMP (five aliquots of 200 nmol/ml added 10 min apart) during anoxia causes complete recovery of ATP levels, and respiratory and transport function after 40 min of reox. Similar additions of adenosine (ADO), or inosine (INO), or Mg-ATP only during reox are less effective. Lactate dehydrogenase (LDH) release after 40 min of anoxia is 30-40% under control conditions, only 10-15% when adenine nucleotides or ADO are added during anoxia, and 20% when INO is added, suggesting that these additions may stabilize the plasma membrane during anoxia and help preserve cellular integrity. During reox, recovery may depend on the entry of ATP precursors and, therefore, we explored the mechanism whereby exogenous ATP increases the intracellular ATP content. Additions of Mg-ATP, Mg-ADP, or Mg-AMP to continuously oxygenated tubules increase cellular ATP content three- to fourfold in 1 h. The added ATP and ADP are rapidly degraded to AMP, and more slowly to ADO, INO, and hypoxanthine. Furthermore, the ATP-induced increase in cellular ATP is abolished by the exogenous addition of adenosine deaminase, which converts extracellular ADO to INO. These results suggest that the increase in cellular ATP requires extracellular ADO. The ADO obtained from the breakdown of AMP may be preferentially transported into the renal cells to be resynthesized into cellular AMP and ATP. PMID- 3350973 TI - Epinephrine facilitates neurogenic vasoconstriction in humans. AB - Numerous studies have suggested that epinephrine may facilitate neural release of NE. There have been no studies in humans that demonstrate the functional significance of this action. To determine whether epinephrine facilitates neurogenic vasoconstriction in humans, we contrasted forearm vasoconstrictor responses to a reflex stimulus (lower body negative pressure [LBNP]) and to intraarterial NE before, during, and 30 min after infusion of epinephrine (50 ng/min) or isoproterenol (10 or 25 ng/min) into a brachial artery. These doses had no systemic effects. We reasoned that if prejunctional stimulation of beta receptors by epinephrine and isoproterenol had functional significance, the vasoconstrictor response to LBNP would be potentiated in comparison to the response to NE (postjunctional mechanism). Studies were done on 23 normal male volunteers. Forearm blood flow was measured with a strain gauge plethysmograph and intraarterial pressure was recorded. The ratio of vasoconstrictor responses to LBNP/NE was used as an index of neural release of the neurotransmitter NE. This ratio increased during infusions of both epinephrine and isoproterenol. 30 min after epinephrine the vasoconstrictor response to LBNP (n = 15) was augmented from +9.9 +/- 2.2 (SE) resistance units (RU) before epinephrine to +16.4 +/- 3.2 RU (P less than 0.05); whereas the response to NE (n = 8) tended to decrease from +8.8 +/- 3.1 RU before to +4.2 +/- 1.2 RU after epinephrine (P greater than 0.05). In contrast, 30 min after isoproterenol the vasoconstrictor responses to LBNP and NE were the same as before isoproterenol. The augmented ratio of responses to LBNP/NE after epinephrine and not after isoproterenol supports the concept that epinephrine, but not isoproterenol, is taken up by the adrenergic terminal, is released subsequently during reflex stimulation, and augments the release of the neurotransmitter NE. These experiments provide the first hemodynamic evidence in humans that epinephrine and isoproterenol facilitate neurogenic vasoconstriction. The sustained effect of epinephrine in contrast to isoproterenol suggests that the late facilitation by epinephrine is related to its neural uptake and subsequent release. PMID- 3350975 TI - Inhibitory effects of volume expansion performed in vivo on transport in the isolated rabbit proximal tubule perfused in vitro. AB - To examine the renal tubular sites and mechanisms involved in the effects of hypooncotic volume expansion (VE) on renal electrolyte excretion, we performed clearance and isolated tubular perfusion studies using intact and thyroparathyroidectomized (TPTX) rabbits. We also examined the effect of VE on luminal brush border transport. In the microperfusion studies, proximal convoluted (PCT) and straight (PST) tubules were taken from rabbits without prior VE or after 30 min of 6% (body wt) VE. Acute VE increased the percentage excretion of Na, Ca, and P in TPTX animals and the percentage and absolute excretions of these ions in intact rabbits. In PST from VE animals, fluid flux (Jv) was depressed compared with Jv in PST from nonVE rabbits: Jv = 0.18 +/- 0.03, (VE) vs. 0.31 +/- 0.03 nl/mm.min, (nonVE) P less than 0.02. Phosphate transport (Jp) in the PST from VE animals was also depressed: JP = 1.58 +/- 0.10 (VE) vs. 2.62 +/- 0.47 pmol/mm.min, (nonVE) P less than 0.05. Similar results were obtained with TPTX animals. In the PCT from VE animals, Jv was decreased (0.49 +/- 0.10 (VE) vs. 0.97 +/- 0.14 nl/mm.min, (nonVE) P less than 0.02), but JP was not affected significantly. Transport inhibition was stable over approximately 90 min of perfusion. In the brush border vesicle studies, sodium dependent phosphate transport was inhibited compared with that in control animals, at the 9-, 30-, and 60-s time points. These findings indicate that the inhibition of renal ionic transport by VE occurs in both PCT and PST and is, in part, the result of a direct effect of VE on tubular transport mechanisms. PMID- 3350974 TI - Proposed heparin binding site in antithrombin based on arginine 47. A new variant Rouen-II, 47 Arg to Ser. AB - Antithrombin Rouen-II, a new inherited variant of antithrombin-III, was found in two members of a family with no definite history of thrombosis. The subjects had normal antigenic concentrations of antithrombin and normal progressive inhibitory activity. However, the variant had defective heparin and heparan sulfate cofactor activities, and was not activated by a synthetic pentasaccharide representing the minimum heparin sequence. The abnormal antithrombin was isolated using heparin Sepharose chromatography, and on electrophoresis at pH 8.6 migrated more anodally than normal. Two-dimensional peptide mapping of tryptic and Staphylococcus aureus V8 protease digests was performed and the abnormal peptide was located by tryptophan staining. Amino acid sequence studies demonstrated a substitution of arginine at residue 47 by a serine. Evidence strongly suggests that arginine 47 is a prime heparin binding site in antithrombin and that it forms part of a proposed positively charged linear site (to which heparin binds) that stretches across the surface of the molecule from the A to the D helix. PMID- 3350976 TI - Association between necropsy evidence of disseminated intravascular coagulation and coagulation variables before death in patients in intensive care units. AB - The necropsy findings in 21 patients on an intensive care unit, on whom coagulation studies had been performed immediately before death, were assessed. Eleven of the patients were retrospectively studied and 10 were reviewed consecutively in a prospective study. Fifteen patients (eight retrospective and seven prospective) had evidence of disseminated intravascular coagulation. Microthrombi were most often found in the lungs and kidneys. The most common abnormal coagulation tests in patients with necropsy evidence of disseminated intravascular coagulation were raised serum concentrations of fibrinogen and fibrin degradation products, prolonged prothrombin time, and reduced platelet counts. Reduced fibrinogen concentrations and a prolonged thrombin time were the least commonly observed abnormalities. There was no difference in either the prevalence or magnitude of abnormality of any particular coagulation variable test result between those patients with evidence of disseminated intravascular coagulation at necropsy and those without. PMID- 3350977 TI - Clinical application of new technique that measures C4d for assessment of activation of classical complement pathway. AB - A new laser nephelometric technique that measures C4d for the assessment of the activation of the classical complement pathway was developed. C4d was isolated from other larger C4 related molecules at a final concentration of polyethylene glycol of 12% and then quantitated by laser nephelometry using a commercially available antiserum, which reacts with C4d determinants. C4d standard (100%) was produced by exhaustive activation of the classical pathway in pooled normal human serum using heat aggregated human immunoglobulin. Serial dilutions of the standard provided a reference curve against which clinical samples were read. Patients with rheumatoid arthritis showed significantly higher C4d values (mean 53.8%) than controls (21.7%; p less than 0.001). The technique proved accurate, rapid, and suitable for the routine laboratory evaluation of complement activation through the classical pathway, and it may be useful in the management of those conditions in which complement activation has a pathogenic role. PMID- 3350978 TI - Widespread expression of intestinal markers in gastric carcinoma: a light and electron microscopic study using BD-5 monoclonal antibody. AB - BD-5 monoclonal antibody reacted with tumour cells in 262 of 316 cases of gastric cancers, including 121 of 134 early, 141 of 182 advanced tumours (p less than 0.01), and 113 of 146 glandular, 72 of 83 diffuse, 22 of 25 mucoid, and 55 of 59 mixed tumours. No difference in reactivity was observed between metastatic and non-metastatic advanced tumours. Immunocytochemical techniques applied to light and electron microscopical specimens of colorectal mucosa and gastric cancer showed that BD-5 immunoreactive material occurred in the Golgi complex, in small clear, to dense cored, cytoplasmic vesicles, and in the glycocalix of the luminal and lateral membranes of normal and neoplastic cells in the glands, as well as in the peripheral membrane of dispersed neoplastic cells. Mucin granules stored in the cytoplasm of goblet cells were unreactive or poorly reactive. Ultrastructural features consistent with colorectal type differentiation were observed in many reactive tumours. Unreactive tumours showing ultrastructural patterns consistent with intestinal differentiation, especially of small bowel type, were also observed. Signs of intestinal differentiation, including BD-5 immunoreactivity, often occur in gastric cancer, irrespective of histological type and stage of disease. PMID- 3350979 TI - Autosomal recessive distal myopathy. AB - Five patients with an autosomally recessively transmitted distal myopathy were investigated. Of these, three belonged to a single sibship. Studies included electromyography, histological examination of muscle tissue, histochemical, electron microscopical, and biochemical analyses. One of the cases resembled the Nonaka form while the others were regarded as expressions of the commoner variety of recessive distal dystrophy. PMID- 3350980 TI - Reduced concentrations of selenium in mild Crohn's disease. AB - The concentrations of selenium, zinc, and copper were determined in whole blood, plasma, and leucocytes in 20 patients with relatively mild Crohn's disease, nine of whom were being treated with steroids, and compared with those of a control group. There was a significant decrease in the concentration of selenium in the leucocytes as well as in whole blood and plasma in the patients. Steroids seemed to affect only the concentrations of zinc and copper in plasma. The concentrations of copper and zinc in whole blood, plasma, and leucocytes in patients not taking steroids were not significantly different from those of the control group. The observations suggest that those patients with an apparently satisfactory whole body concentration of copper and zinc may still be at risk of a decrease in the body content of selenium. PMID- 3350982 TI - Incidence of vaginal Weeksella virosa (formerly group IIf). AB - The antimicrobial susceptibilities, biochemical properties, and cultural characteristics of six strains of Weeksella virosa (formerly group IIf) were determined. The main characteristics of this non-fermentative organism were production of cytochrome oxidase, gelatinase, and indole, but a lack of saccharolytic activity. A study was then made of the isolation rates of Weeksella virosa from high vaginal swabs from 300 women: a healthy control group (n = 100), a general group with symptoms of vaginal infection (n = 100), and 100 women from a remand centre, where likelihood of exposure to sexually transmitted disease might be expected to be higher. The incidence of Weeksella virosa was found to be 2% in the first two groups. This suggests that, irrespective of the presence of pathogens, the incidence of the species in the general female population is around 2%. A much higher incidence (15%) was found in the third group, suggesting sexual transmission of the organism. PMID- 3350981 TI - Quantitative method for determining serum alkaline phosphatase isoenzyme activity: estimation of intestinal component. AB - Intestinal alkaline phosphatase activity was measured using levamisole inhibition, and results were compared with a previously reported method using L phenylalanine. Sixty two per cent intestinal, 39% placental, and 1.3% of either bone or liver alkaline phosphatase activity remained when alkaline phosphatase activity was inhibited in a 2-amino-2-methyl-1-propanol (AMP) buffer reagent system with 10 mmol/l levamisole (final assay concentration 8.1 mmol/l). The assay imprecision (SD) was 0.6 U/l compared with 3.9 U/l using L-phenylalanine for specimens with total alkaline phosphatase activity less than 250 U/l (reference range 30-120 U/l). In serum pools with raised total alkaline phosphatase activity errors in recovered intestinal activity were small (usually less than 3 U/l) when intestinal alkaline phosphatase was added. Much larger errors and many underestimated results were found using L-phenylalanine. For non haemolysed specimens it is concluded that an assay based on levamisole inhibition provides a better measure of intestinal alkaline phosphatase activity than L phenylalanine. PMID- 3350984 TI - Use of microcomputer for histopathology: system using IBM PC and dBaseIII. AB - A microcomputer program for use in the storage and retrieval of histopathology records is described. The program was written using dBaseIII, a commercially available data management system. The program provides for efficient storage and rapid retrieval of pathology reports and facilitates clinical research. Downloading of data on to a mainframe computer is possible. PMID- 3350983 TI - Quality assessment in cervical cytology: a pilot study. AB - A pilot study of an external quality assessment scheme was run between February 1985 and September 1986 to (i) assess the feasibility of running one from a district general hospital; (ii) to estimate the time required to organise and run it with a computer; (iii) to provide sound statistical results with which future schemes could be compared. Seven laboratories participated, and the 20 smears selected from each laboratory were circulated in three rounds in batches of seven, seven, and six according to a prearranged order. Results analysed using the kappa statistic showed moderate levels of interlaboratory agreement, with complete agreement emerging only on a small proportion of cases. PMID- 3350985 TI - Comparison of hospital staff performance when using desk top analysers for "near patient" testing. AB - The quality and reliability of four desk top analysers were evaluated. In the context of an outpatient clinic, intensive care unit, and a mock up of a physician's office. Seventeen nurses, 14 physicians, and 12 medical office personnel took part in the study. The instruments and tests evaluated were Reflotron (glucose, cholesterol, triglycerides, gamma-glutamyl transferase), Seralyzer (creatinine, glucose, potassium, aspartate aminotransferase), Vision (glucose, (creatinine, glucose, potassium, aspartate aminotransferase), Vision (glucose, urea, cholesterol, triglycerides alkaline phosphatase, uric acid), and DT60 (sodium, potassium, glucose, amylase, uric acid and creatinine). Of the 320 tests performed on the Vision, only two differed by more than 10% between the specialist staff and other groups. For those performed on the Seralyzer, 95 of 254 results differed by more than 10%, 19 of 199 by more than 10% for the Reflotron, and 50 of 318 by more than 10% for the DT60. In general, the nurses were more adept at using the analysers than the physicians and medical office personnel. PMID- 3350987 TI - Parasites in faecaliths. PMID- 3350986 TI - Simple latex agglutination method for typing pneumococci. PMID- 3350988 TI - Role of fine needle aspiration cytology. PMID- 3350989 TI - Use of microcomputers to facilitate costing in pathology laboratories. PMID- 3350990 TI - The Clinical Pharmacology Consultation Service: results of a physician survey before and after implementation. AB - A total of 175 physicians were surveyed by questionnaire before a Clinical Pharmacology Consult Service was started. Of those that responded, 72% thought the service would be helpful, although 40% said they would use the service no more than once a month. Most physicians (75%) preferred self-initiated consultations to automatic surveillance. Ninety-two percent believed a physician should be involved in making drug recommendations. A second questionnaire was circulated 30 months later. Actual use of the service closely paralleled the results of the first survey. There was an increased preference for automatic surveillance (5% vs 32%) and many physicians (48%) indicated they felt comfortable accepting drug consultations from a pharmacist or clinical pharmacist. Despite a general attitude of acceptance, the majority of respondents ranked the Clinical Pharmacology Consult Service last as a source of drug information. PMID- 3350992 TI - Multiple-dose cimetidine administration does not influence the single-dose pharmacokinetics of quinapril and its active metabolite (CI-928). AB - The potential effect of cimetidine on the pharmacokinetic profiles of quinapril and its active metabolite CI-928 was evaluated in eight healthy volunteers. Each subject received a single 40-mg quinapril dose on days 1 and 12 and cimetidine 300 mg four times daily on days 8 through 13. Serial blood and urine samples were collected for assay of quinapril and CI-928 concentrations. No statistically significant differences were observed in quinapril or CI-928 Cmax, tmax, AUC(0 infinity), beta, or percent of dose excreted in urine values for quinapril administered alone and in combination with cimetidine. Therefore, multiple-dose cimetidine administration does not influence the single-dose pharmacokinetics of quinapril and its active metabolite, CI-928, in healthy volunteers. PMID- 3350991 TI - Effect of oral cibenzoline on steady-state digoxin concentrations in healthy volunteers. AB - The effect of oral cibenzoline on steady-state digoxin concentrations was studied in 12 healthy subjects ranging from 41 to 55 years of age. Each subject received an oral dose of 0.25 mg or 0.375 mg digoxin once daily for 27 days. On days 14 to 21, 160 mg of oral cibenzoline were administered concomitantly every 12 hours for a total of 15 doses. Plasma digoxin concentration-time profiles obtained before, during, and after cibenzoline coadministration were compared to determine the effect of oral cibenzoline on steady-state digoxin concentrations. The maximum plasma concentration, time of maximum concentration, area under the curve during a dosing interval and steady-state trough plasma concentration for digoxin, during and after concomitant doses of cibenzoline were similar to those before administration, indicating that cibenzoline did not affect the pharmacokinetics of digoxin. In addition, plasma cibenzoline concentration-time profiles after the first and last dose of cibenzoline were similar to those observed in previous studies in which multiple doses of cibenzoline alone were administered. The results of this study indicate that there is no pharmacokinetic interaction between digoxin and cibenzoline when the two drugs are coadministered to healthy subjects in multiple doses. PMID- 3350993 TI - Naltrexone: lack of effect on hepatic enzymes. AB - A number of studies have established the clinical efficacy of naltrexone in the treatment of opiate addiction. However, questions have been raised regarding its hepatotoxic potential and warnings have been given prominence in the package insert regarding its use for those with even less severe liver disease. The current study monitored 53 male patients receiving naltrexone 350 mg weekly for 12 weeks. The lactic acid dehydrogenase (LDH) and serum glutamic oxalacetic transaminase (SGOT) levels were determined at pretreatment and at monthly intervals thereafter for three months. LDH and SGOT were found to drop significantly from baseline over this three-month period. This decrease appeared most notable for those with pretreatment hepatic enzyme levels exceeding the normal range. Moreover, changes in hepatic enzyme levels were not consistently correlated with the patients use of illicit drugs such as opioids, benzodiazepines, cocaine, barbiturates, and amphetamines. Based on these data, we have concluded that contrary to cautions implied in the naltrexone package insert, the benefit of admitting patients with the sole problem of elevated hepatic enzymes generally exceeds the risk. PMID- 3350994 TI - Relative and absolute bioavailability of prednisone and prednisolone after separate oral and intravenous doses. AB - A randomized, four-way cross-over study was conducted in eight healthy male volunteers to determine the relative and absolute bioavailability of prednisone (PN) and prednisolone (PL). PN and PL were administered as single, oral 10-mg tablet doses and as 10-mg zero-order 0.5-hour intravenous infusions. Comparable mean PN and PL maximum plasma concentrations (Cmax), times for Cmax, areas under the plasma concentration-time curves (AUC), and apparent elimination rate constants between tablet treatments demonstrated that PN and PL tablets were bioequivalent. Absolute bioavailability (F) determinations based on plasma PL concentrations were independent of which IV treatment was used as reference and indicated complete systemic availability of PL from both PN and PL tablets. However, F based on plasma PN data was contradictory. Using IV PN as reference, approximately 70% systemic availability was observed from both tablets, whereas using IV PL as reference, systemic availability was greater than unity. PN and PL are model compounds that exemplify the difficulties involved in accurately determining the relative and absolute bioavailability of substances that undergo reversible metabolism. PMID- 3350996 TI - Behavioral and cognitive toxicity related to elevated plasma tricyclic antidepressant levels. AB - Tricyclic antidepressants (TCAs) have been occasionally reported to cause delirium, probably via a central antimuscarinic action. Nine of 16 patients with plasma TCA levels greater than 450 ng/ml developed cognitive or behavioral toxicity, compared with only one of 15 patients in a control group with plasma TCA levels between 150 and 450 ng/ml. The clinician should be aware of this potential adverse effect of TCA therapy, which may be easily preventable through the combination of careful clinical monitoring and liberal use of plasma TCA levels. PMID- 3350995 TI - Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status. AB - The mechanism of cephalosporin-induced hypoprothrombinemia has been investigated in hospitalized patients, with respect to cephalosporin structure, vitamin K metabolism, and vitamin K status. Cephalosporins containing side chains of N methylthiotetrazole (latamoxef, cefmenoxime, cefoperazone, cefotetan, cefamandole) or methyl-thiadiazole (cefazolin) all caused the transient plasma appearance of vitamin K1 2,3-epoxide in response to a 10-mg intravenous dose of vitamin K1, whereas two cephalosporins without a heterocyclic side chain (cefotaxime and cefoxitin) did not. The plasma accumulation of vitamin K1 2,3 epoxide was qualitatively similar to, but quantitatively less than, that produced by the oral anticoagulant phenprocoumon. Patients eating normally had plasma vitamin K1 concentrations (176 to 1184 pg/mL) that were within the normal range (150 to 1550 pg/mL) and their clotting tests remained consistently normal for all antibiotics tested. Patients on total parenteral nutrition had lower plasma vitamin K1 concentrations (50 to 790 pg/mL) but normal clotting before starting antibiotic therapy. Of 19 parenterally fed patients, all seven treated with latamoxef developed hypoprothrombinemia, PIVKA-II and a decrease of protein C within four days whereas 12 patients treated with cefotaxime or cefoxitin showed no clotting changes. Latamoxef-associated hypoprothrombinemia was readily reversible by 1 mg of vitamin K1 given intravenously, but hypoprothrombinemia and sub-normal plasma vitamin K1 could recur within two to three days. The data suggest that NMTT-cephalosporins are inhibitors of hepatic vitamin K epoxide reductase and that a lower nutritional-vitamin K status predisposes to hypoprothrombinemia. PMID- 3350997 TI - The relationship of haloperidol concentrations to therapeutic response. AB - Data from pharmacokinetics studies that examined the relationship of haloperidol serum concentrations and therapeutic response in schizophrenic patients were reexamined utilizing the method of logistic regression analysis. A linear rather than a curvilinear relationship was obvious between serum haloperidol concentration and therapeutic response according to both the regression analysis and inspection of the distribution of the data. It was concluded that a serum haloperidol concentration in the range of 9 to 15 ng/ml was associated with a 30% decrease in the total Brief Psychiatric Rating Scale (BPRS) score. Haloperidol concentrations above these appear unlikely in the majority of patients to produce any additional reduction of symptoms. The BPRS psychosis factor finding suggested an analogous finding for serum haloperidol concentrations between 12 and 17 ng/ml. The analyses suggest that the probability of response to haloperidol seems to reach a point of diminishing return at concentrations of approximately 9 to 17 ng/ml. Serum concentrations above this limit do not appear to either decrease or increase the probability of response. PMID- 3350998 TI - S-adenosyl-L-methionine in the treatment of Alzheimer's disease. AB - Patients with Alzheimer's disease (AD) have an apparent abnormality possibly representing an increase in the average fluidity of their cell membranes. Changes in membrane fluidity of similar magnitude to those observed in AD have been noted to lead to marked alterations in cell function. Therefore, the changes in fluidity observed in AD may be related to the symptoms of that disorder, representing either an underlying cause of dysfunction or cellular attempts to compensate for dysfunction in AD. To test these possibilities, we administered S adenosyl-L-methionine (SAMe), an agent shown to increase membrane fluidity in animals, to patients with AD. Treatment with SAMe led to marked increases in membrane fluidity. However, it produced neither improvement nor worsening of symptoms. The results imply that while SAMe may be useful for other conditions associated with altered membrane fluidity (such as normal aging), changing membrane fluidity per se is not likely to lead to marked changes in symptoms in AD. PMID- 3350999 TI - Multiple-dose pharmacokinetics of imipramine and its major active and conjugated metabolites in depressed patients. AB - Imipramine (IMI) and its active metabolites, desipramine (DMI), 2 hydroxyimipramine (2-OH-IMI), and 2-hydroxydesipramine (2-OH-DMI), were assayed by high pressure liquid chromatography in the serum and urine of 14 depressed patients after 1 week of twice-daily treatment with 100 mg of IMI. The concentrations of the glucuronide conjugates of 2-hydroxyimipramine (GA-O-IMI) and 2-hydroxydesipramine (GA-O-DMI) were assessed via enzyme hydrolysis. The range of serum concentrations of IMI and DMI was 65 to 1,064 ng/ml with slight elevation in total active components caused by inclusion of the unconjugated hydroxy metabolites. The average of total active compounds in smokers (239 ng/ml) was less (p less than 0.1) than in nonsmokers (524 ng/ml). The mean serum concentration ratios were 0.24 for 2-OH-IMI/IMI and 0.50 for 2-OH-DMI/DMI ratios, whereas the DMI/IMI ratio was 1.88, indicating more extensive accumulation of DMI. Appreciable glucuronide conjugate accumulation occurred with average serum concentration ratios of 8.13 for GA-O-IMI/2-OH-IMI and 6.22 for GA-O-DMI/2-OH DMI. Covariance occurred in metabolite/precursor ratios indicating intrapatient similarities in formation/disposition rates of the hydroxy pairs and the conjugate metabolite pairs. Renal clearances of 2-OH-DMI were 35 to 267 ml/min, whereas those of the conjugates were only 10 to 110 ml/min. Total urinary recovery of these metabolites was similar to that reported previously for single IMI doses. The data indicate accumulation of substantial serum concentrations of glucuronide conjugates after therapeutic doses of IMI in depressed patients and similarities within patients in disposition of metabolite pairs. PMID- 3351001 TI - View from the Nation's Capital. FDA moves forward (and backwards) on a number of simmering issues. PMID- 3351002 TI - View from the Nation's courts. PMID- 3351000 TI - Persistence of fluphenazine in plasma after decanoate withdrawal. AB - We discontinued fluphenazine decanoate using a double-blind, crossover random order design, in 12 recent onset clinically stable schizophrenics who had been given fluphenazine decanoate 12.5 mg intramuscularly every 2 weeks for at least 1 year prior to drug withdrawal. Each condition (drug or placebo) lasted 12 weeks. Using a radioimmunoassay verified by comparison to a gas chromatographic-mass spectrometric method, plasma fluphenazine levels were measured every 2 weeks during drug continuation and drug withdrawal conditions. No patient relapsed over the 24-week period of the study. Mean fluphenazine levels between drug continuation and withdrawal conditions showed a progressively larger difference over time, although significant differences were not seen until week 8. By week 12 after drug withdrawal, 33% of subjects still showed notable plasma fluphenazine levels. On the basis of our preliminary findings, we suggest that 2 week intervals between injections may be too short and that wider intervals may achieve similar clinical results. PMID- 3351003 TI - A dose range-finding study of buspirone in geriatric patients with symptoms of anxiety. PMID- 3351004 TI - The immune system and its control: a possible model in herpes virus infections. PMID- 3351006 TI - Clonazepam-induced reduction in serum desipramine concentration. PMID- 3351005 TI - Psychopharmacology of drugs effective in obsessive-compulsive disorder. PMID- 3351007 TI - Cholinergic rebound following trazodone withdrawal? PMID- 3351008 TI - Acute myocardial failure following amoxapine intoxication. PMID- 3351009 TI - Visual hallucinations on low dose amitriptyline. PMID- 3351010 TI - Effectiveness of desipramine in the treatment of dyshidrosis. PMID- 3351011 TI - Delirium induced by association of propranolol and maprotiline. PMID- 3351012 TI - Comment on "Pharmacokinetics of lithium in the elderly". PMID- 3351013 TI - Leukoderma punctata. AB - Thirteen patients with vitiligo (1 segmental, 4 focal, 8 generalized) aged 7 to 38, most of them female children, developed numerous punctate hypopigmented and achromic spots. The spots measured 0.5 to 1.5 mm and were located primarily on the sun-exposed areas of the extremities; they appeared following treatment with PUVASOL. Two of these patients experienced a reduction of this leukodermic defect, whereas the remaining patients showed a stable clinical course. Dopa and Fontana stains disclosed, in most cases, decreased but not absent functional melanocytes and a marked reduction of melanin. Ultrastructural studies demonstrated slight to severe damage of keratinocytes and melanocytes similar to that previously reported in vitiligo patients. The phototoxic effect of PUVASOL therapy is suggested as a possible etiologic factor in these patients. A probable relationship among idiopathic guttate hypomelanosis, leukoderma punctata, and vitiligo is discussed. PMID- 3351014 TI - Superficial granulomatous pyoderma: a localized vegetative form of pyoderma gangrenosum. AB - Twenty-five patients had superficial ulcerative and vegetative pyoderma with granulomatous histologic findings. Healing occurred without systemic corticosteroid therapy in all but three patients. All patients had clinical pyoderma gangrenosum. In five patients the lesion occurred after surgery of the skin. Histopathologic study of 40 biopsy specimens showed focal neutrophilic abscesses of the papillary dermis, often with peripheral palisading histiocytes and foreign-body giant cells. Pseudoepitheliomatous, vegetative hyperplasia and sinus tract formation were observed frequently. All patient had massive areas of plasmacytosis, and 13 had eosinophils. Granulation tissue, hemorrhage, and fibrosis were additional features in some areas. Foreign material in the lesions was considered unimportant, except in one patient with a starch granuloma. Therapy with local corticosteroids, minocycline, tetracycline, or sulfa drugs resulted in healing in 15 patients. We believe that we have identified a localized, limited form of chronic superficial pyoderma gangrenosum with verrucous and ulcerative lesions and a granulomatous histologic appearance that represents a unique pattern of this disease in some patients. PMID- 3351015 TI - Necrobiosis lipoidica diabeticorum: a clinicopathologic study. AB - Necrobiosis lipoidica diabeticorum is an unusual dermatologic condition with a characteristic clinical appearance and a clear association with diabetes mellitus. There is currently no treatment that reverses the atrophic changes associated with this lesion. We have carried out a clinicopathologic study on 15 subjects and, in addition, have reviewed 10 further biopsy specimens of necrobiosis lipoidica diabeticorum. We found a frequent association of necrobiosis lipoidica diabeticorum with other chronic complications of diabetes mellitus, including limited joint mobility. It is possible that nonenzymatic glucosylation or other changes in collagen may be important in the etiology of necrobiosis lipoidica diabeticorum and the limited joint mobility. We confirmed that cutaneous anesthesia is usually present in the necrobiosis lipoidica diabeticorum lesions. With the use of an antibody to S100 protein and an immunohistochemical method, there was an apparent decreased number of nerves in the skin lesions. We suggest that sensory loss results from local destruction of cutaneous nerves by the inflammatory process. Finally, in six elliptical biopsies extending into clinically normal skin, we demonstrated that the inflammatory infiltrate of necrobiosis lipoidica diabeticorum extended from the lesion into apparently normal skin surrounding clinically active lesions. Thus, intradermal steroids might be administered to perilesional areas surrounding active lesions in the hope of halting progression. PMID- 3351016 TI - Hyperimmunoglobulin E and impaired neutrophil functions in a case of pyoderma gangrenosum: effect of clofazimine. PMID- 3351017 TI - Addison's disease and lupus vulgaris: report of a case. PMID- 3351018 TI - Dermatitis herpetiformis in a patient with acquired immunodeficiency syndrome related complex. PMID- 3351019 TI - Chronic varicella zoster infection in acquired immunodeficiency syndrome. PMID- 3351020 TI - Tanning bed warts. PMID- 3351021 TI - An unusual case of recurrent painful erythema. PMID- 3351022 TI - Patient and physician delay in melanoma diagnosis. AB - The sequence of events leading ultimately to the diagnosis and treatment of malignant melanoma was investigated. We conducted interviews with 275 patients and the physicians whom they had consulted regarding their suspicious lesions before their eventual referral to a melanoma center. An average of 1 year elapsed from the time that patients first noticed a new or changed lesion and the date of diagnosis. Major components of delay were attributable to both patients and physicians. An average of 6 months elapsed between patients' recognition of a new or changed lesion and their realization that the lesion was suspicious. For 21% of cases, at least 2 months elapsed between physicians' observation of lesions and a definitive diagnosis of malignant melanoma, and 13% were diagnosed a minimum of 4 months following a visit to the physician. Patients routinely cannot distinguish between melanomas and moles. Physicians do not always diagnose melanoma accurately or act promptly in response to suspicious lesions. We have yet to take adequate advantage of the unique opportunity for early detection and cure in this readily visible, rapidly increasing malignancy. PMID- 3351023 TI - Trehalase from the bean-shaped accessory glands and the spermatophore of the male mealworm beetle, Tenebrio molitor. AB - In Tenebrio molitor, male adults transfer sperm to the female via a spermatophore or sperm sac. The spermatophore is formed from secretions of the bean-shaped accessory glands (BAGs) and the tubular accessory glands (TAGs) of the male beetle. Trehalase is found in the adult BAGs. During the pupal stage, the activity in the BAGs was very low. After adult ecdysis, the total activity increased 100-fold from 0 days to 6 days and reached maximum levels at 9 days. The specific activity increased 20-fold from the time of ecdysis to 6 days thereafter. In the 10 day adult, trehalase levels in testes, seminal vesicles, vas deferens, TAGs, or ejaculatory ducts, were lower by two orders of magnitude than in the BAGs. However, the specific activity in the spermatophore was similar to that in the BAGs. Trehalases in the BAGs and the spermatophores showed very similar properties (soluble, optimum pH of 5.75 and Km value of 5.4 mM for trehalose). Thus trehalase appears to be secreted from the BAGs and becomes incorporated into the spermatophores. PMID- 3351024 TI - Thermoregulation, gas exchange, and ventilation in Adelie penguins (Pygoscelis adeliae). AB - Adelie penguins (Pygoscelis adeliae) experience a wide range of ambient temperatures (Ta) in their natural habitat. We examined body temperature (Tb), oxygen consumption (VO2), carbon dioxide production (VCO2), evaporative water loss (mH2O), and ventilation at Ta from -20 to 30 degrees C. Body temperature did not change significantly between -20 and 20 degrees C (mean Tb = 39.3 degrees C). Tb increased slightly to 40.1 degrees C at Ta = 30 degrees C. Both VO2 and VCO2 were constant and minimal at Ta between -10 and 20 degrees C, with only minor increases at -20 and 30 degrees C. The minimal VO2 of adult penguins (mean mass 4.007 kg) was 0.0112 ml/[g.min], equivalent to a metabolic heat production (MHP) of 14.9 Watt. The respiratory exchange ratio was approximately 0.7 at all Ta. Values of mH2O were low at low Ta, but increased to 0.21 g/min at 30 degrees C, equivalent to 0.3% of body mass/h. Dry conductance increased 3.5-fold between -20 and 30 degrees C. Evaporative heat loss (EHL) comprised about 5% of MHP at low Ta, rising to 47% of MHP at Ta = 30 degrees C. The means of ventilation parameters (tidal volume [VT], respiration frequency [f], minute volume [VI], and oxygen extraction [EO2]) were fairly stable between -20 and 10 degrees C (VT did not change significantly over the entire Ta range). However, there was considerable inter- and intra-individual variation in ventilation patterns. At Ta = 20-30 degrees C, f increased 7-fold over the minimal value of 7.6 breaths/min, and VI showed a similar change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351025 TI - Dynamics of cardiorespiratory function in Standardbred horses during different intensities of constant-load exercise. AB - Six Standardbred horses were used to evaluate the time course of pulmonary gas exchange, ventilation, heart rate (HR) and acid base balance during different intensities of constant-load treadmill exercise. Horses were exercised at approximately 50%, 75% and 100% maximum oxygen uptake (VO2 max) for 5 min and measurements taken every 30 s throughout exercise. At all work rates, the minute ventilation, respiratory frequency and tidal volume reached steady state values by 60 s of exercise. At 100% VO2 max, the oxygen consumption (VO2) increased to mean values of approximately 130 ml/kg.min, which represents a 40-fold increase above resting VO2. At the low and moderate work rates, VO2 showed no significant change from 30 s to 300 s of exercise. At the high work rate, the mean VO2 at 30 s was 80% of the value at 300 s. The HR showed no significant change over time at the moderate work rate but differing responses at the low and high work rates. At the low work rate, the mean HR decreased from 188 beats/min at 30 s to 172 beats/min at 300 s exercise, whereas at the high work rate the mean HR increased from 204 beats/min at 30 s to 221 beats/min at 300 s exercise. No changes in acid base status occurred during exercise at the low work rate. At the moderate work rate, a mild metabolic acidosis occurred which was nonprogressive with time, whereas the high work rate resulted in a progressive metabolic acidosis with a base deficit of 16 mmol/l by 300 s exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351027 TI - Echocardiographic-like angled views of the heart by MR imaging. AB - Cardiac magnetic resonance (MR) imaging has developed rapidly to rival echocardiography as a noninvasive imaging modality. Anatomic detail may exceed that currently available using echocardiography techniques, and the ability to image moving protons may compete with Doppler color flow mapping in detecting valvular diseases and shunts. Because of the considerable clinical experience with echocardiography, as angled MR imaging planes become available as standard software packages, it may be useful for MR cardiac imaging to use standard, accepted echocardiographic nomenclature and imaging planes. This article describes the principles used to obtain long and short axis MR images that are comparable with echocardiographic imaging planes. Diagrams and illustrations are provided to orient the viewer using nomenclature common to echocardiography. These views may eventually be useful for functional analysis of the left ventricle and for detection and evaluation of valvular heart disease and intracardiac shunts. PMID- 3351028 TI - Atypical transmural thoracic lipoma: CT diagnosis. AB - Two cases of transmural thoracic lipomas demonstrate a pattern of rib involvement that has not been previously reported. The lipomas presented with an otherwise characteristic appearance on plain radiography and CT. PMID- 3351026 TI - Influence of increased catecholamine levels in blood plasma during cold adaptation and intramuscular infusion on thresholds of thermoregulatory reactions in guinea-pigs. AB - Catecholamines and some of their metabolites were determined in urine and blood plasma of guinea-pigs before, during and after acclimation to a cold or warm environment. During adaptation to 5 degrees C the amounts of noradrenaline in plasma and 24-h urine samples continuously increased up to 600% compared with values obtained at an ambient temperature of 22 degrees C. Higher levels of dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol further indicated an increased turnover of noradrenaline during cold adaptation. Acclimation to an ambient temperature of 28 degrees C reduced the peripheral release of noradrenaline in comparison to the release observed at 22 degrees C. Cold-induced increases in metabolic rate and electrical muscle activity both occur at a considerably lower mean body temperature in cold-than in warm-adapted guinea pigs. The shift of thermoregulatory cold defence reactions to a lower mean body temperature could also be observed in warm-adapted animals after intramuscular infusion of noradrenaline in amounts comparable to those released during cold adaptation. It is concluded that high peripheral sympathetic activity directly or indirectly inhibits noradrenergic neurons in the lower brain stem that modulate the thermoregulatory control system by means of their afferents to the hypothalamus. As a consequence of this peripheral influence the thermoregulatory set point is shifted to a lower mean body temperature. PMID- 3351029 TI - CT evaluation of mediastinal lymph nodes in primary Sjogren syndrome. AB - Computed tomography was used to evaluate mediastinal lymph nodes of 25 patients with primary Sjogren syndrome (pSS) and in 38 control subjects. Abnormally enlarged nodes, according to accepted CT criteria, were detected in four pSS patients and in 10 control subjects (differences not significant). The presence of enlarged mediastinal nodes did not correlate with peripheral lymphadenopathy, splenomegaly, parotid enlargement, or cryoglobulinemia in the pSS group. One pSS patient with pseudolymphoma and another with non-Hodgkin lymphoma did not have enlarged mediastinal lymph nodes. Our results suggest that the detection by CT of slightly enlarged mediastinal nodes, invisible in plain radiography, in pSS patients is of uncertain clinical significance. PMID- 3351030 TI - The value of opacification of the esophagus by low density barium paste in computer tomography of the thorax. AB - A 3% barium paste was used in the CT evaluation of 100 normal and 60 abnormal esophagi. Successful esophageal opacification occurred in 87% of both groups. In cases of extrinsic disease involving the esophagus the contrast medium administration assisted in separating the esophagus from adjacent mass lesions, as well as identifying displacement, compression, proximal dilatation, and length of involvement. In cases of esophageal carcinoma the contrast medium administration assisted in the measurement of wall thickness and length of the lesion as well as identification of the site of origin of the tumor. The contrast medium was simple to administer, well tolerated, and did not produce scan artifacts. PMID- 3351032 TI - Preoperative assessment of the extension of rectal carcinoma: correlation of MR, surgical, and histopathologic findings. AB - Nineteen patients with rectal carcinoma were evaluated prospectively. The extent of tumor and the relationship of the tumor to the levator ani muscle were studied as this determines the choice of the surgical procedure (abdominoperineal resection versus low anterior resection). Peroperative assessment and detailed evaluation of the pathologic specimens were correlated with magnetic resonance (MR) features. Magnetic resonance staging and surgical findings were at variance in four of 15 cases (27%). Magnetic resonance had sensitivities and specificities of 75 and 100% in the detection of perirectal growth. Magnetic resonance demonstrated invasion of adjacent pelvic side wall and sacrum in two of two cases. The comparison with TNM classification demonstrated that MR correctly staged 15 of 19 cases (79%). This study shows that MR is a good examination to evaluate the involvement of perirectal fatty tissues and adjacent structures. The low prevalence of involved lymph nodes in our cases prevents significant positive predictive values. Nevertheless, MR can help to select patients for local excision or for preoperative radiotherapy. PMID- 3351031 TI - Computer tomography of congenital absence of the left lobe of the liver. AB - Computed tomography of absence of the left lobe of the liver is described. Liver scintigraphy may be misinterpreted as indicating tumor of the left lobe. Computed tomography correctly identifies absence of the left lobe and compensatory hyperplasia of the caudate lobe. Two illustrative cases with a peculiar "tongue like projection" of the caudate lobe are presented. PMID- 3351033 TI - Computed tomography of midline cysts of the prostate. AB - Midline cysts in the male pelvis are a confusing entity due to their relatively infrequent presentation and the uncertainty as to their origin and classification. We report on CT appearance of four cases of midline prostatic cysts. Ultrasound correlation was available in one case. Two patients presented with lower urinary tract symptoms (hematospermia and/or hematuria), and two were asymptomatic, with one case detected on physical examination and one found incidentally on CT. Computed tomography demonstrated a characteristic sharply marginated, low density, homogeneous midline cyst within the prostate. On ultrasound a well defined midline anechoic cystic mass was seen. These cases are illustrated and a discussion of cystic masses in the male pelvis is included. PMID- 3351034 TI - MR demonstration of extensive pelvic involvement in vulvar hemangiomas. AB - Magnetic resonance imaging of two patients with vulvar hemangiomas noninvasively demonstrated unexpected pelvic involvement. Magnetic resonance is an excellent method for initial evaluation and follow-up of these lesions. PMID- 3351035 TI - Musculoskeletal desmoid tumors: CT assessment during therapy. AB - Musculoskeletal desmoid tumors can be difficult to characterize and to follow. The rate of regression after radiotherapy is variable, with poor response to chemotherapy and postoperative recurrence being common. Eighteen patients undergoing therapy for proven musculoskeletal desmoid tumors had 52 CT studies, which were assessed to determine the utility of CT in following such patients. Computed tomography was found to offer excellent initial baselines prior to additional treatment and in the early postoperative period and followed the tumor response to treatment. Ultimate tumor response could not be predicted by characteristics of or change in tumor margins, by initial or subsequent tumor CT attenuation, by appearance following intravenous contrast medium, or by tumor location. Decreasing size and stabilization of size in a previously growing lesion were the only reliable signs of response; markedly increasing attenuation heterogeneity suggested but was unreliable as an isolated sign of response. PMID- 3351037 TI - Radiation induced fractures of sacrum: CT diagnosis. AB - Sacral insufficiency fracture due to bone atrophy may develop as a complication of irradiation of pelvic malignancies. Pain is the presenting symptom and the clinical diagnoses most often considered are recurrence of the original malignancy and metastatic disease. Computed tomography provides the most specific information helpful for the detection of these fractures and for exclusion of recurrent malignancy. PMID- 3351036 TI - CT analysis of proximal femoral trabecular pattern simulating skeletal pathology. AB - The proximal femoral trabecular pattern was studied in 20 patients, six cadavers, and 20 macerated specimens using plain film radiography and CT. A distinctive pattern of increased radiodensity in the proximal femur is described in patients and specimens with osteoporosis and osteoarthritis. The appearance is similar to that of an enchondroma or bone infarct. This pattern may be explained by biomechanical principles and is created by unmasking or hypertrophy of preexistent, reinforcing trabeculae. Confusion with osseous pathology can be avoided if the radiologist is aware of this pattern. PMID- 3351038 TI - Evaluation of CT techniques for reducing artifacts in the presence of metallic orthopedic implants. AB - Metallic intramedullary orthopedic implants generate artifacts that can markedly degrade transaxial CT images. The artifacts, typically seen as starburst streaking, result primarily from reconstructions involving missing projection data. Two approaches are clinically available to reduce the artifacts around orthopedic implants. These are (a) the imaging of implants with lower attenuation coefficients or smaller path lengths (less attenuating objects) and (b) the planar reformatting of image data. The sizing accuracy of these two approaches was quantified using phantoms and the efficacy using cadaveric femoral specimens. Results demonstrated that metal artifacts may be reduced and accurate bony dimensional data obtained. PMID- 3351039 TI - Vertebral mineral determination by quantitative computed tomography (QCT): accuracy of single and dual energy measurements. AB - Quantitative CT (QCT) studies of trabecular vertebral bone tissue have been carried out in vitro on a GE CT/T 9800 scanner. Results of both single energy (SE) 80 kVp and dual energy (DE) 80/140 kVp QCT data are compared with chemical mineral analysis to determine accuracy. We examined 62 vertebral specimens, from 28 cadavers (19 male and 9 female with an age range of 19-93 years, mean = 60.4). Averaging the results of all vertebral bodies of the same individual for SEQCT versus ashweight, we found a correlation coefficient (r) of 0.94 (p less than 0.0001), a standard error of the estimate (SEE) of 12.2 mg/cm3 (calibrated to K2HPO4), with a coefficient of variation (CV) of 13.2% and an average underestimation of bone mineral content of 18.7 mg/cm3. The corresponding DEQCT results were r = 0.98 (p less than 0.0001), SEE = 7.4 mg/cm3, CV = 7.0%, and an average underestimation of 4.9 mg/cm3. The SE and DE results are correlated with r = 0.98 (p less than 0.0001), SEE = 8.0 mg/cm3, and CV = 8.7%. From our SEQCT data and the results of the chemical analysis of bone mineral and fat content we calculated a fat sensitivity of 7.7 mg/cm3 K2HPO4 per 100 mg/cm3 fat change for our scanner. Using an average fat variability of 87.5 mg/cm3, this leads to a fat related uncertainty for the normative SEQCT data of 6.7 mg/cm3, which is far lower than the normal biological variation of 29.4 mg/cm3. Using tabulated normative data on fat content versus age and versus mineral content of 188 vertebral specimens from five collaborating centers, we derived a correction algorithm for QCT measurement that reduces our average underestimation to 0.88 mg/cm3 with an SEE of 12.1 mg/cm3. Hence, this correction procedure can be used to estimate the fat corrected absolute mineral density for research purposes or for scanners with high fat sensitivity. For the GE CT/T 9800 scanner, with a relatively low fat to mineral sensitivity at 80 kVp, the correction procedure is generally not recommended for clinical studies since it minimizes the average fat induced error but does not reduce the residual, partially fat related uncertainty. Finally, since the fat related uncertainty is small compared to biological variation, the correlation is high between SEQCT and DEQCT, and the radiation dose is lower and the precision higher for SEQCT, we suggest that most clinical diagnostic studies using the GE CT/T 9800 scanner for bone mineral determination employ SEQCT at 80 kVp. PMID- 3351040 TI - Susceptibility induced MR line broadening: applications to brain iron mapping. AB - Magnetic susceptibility variations due to the presence of iron in neural tissue can result in a shift of local resonance frequency, decreased T2 resulting from water diffusion through local field gradients, and line broadening due to field inhomogeneity within a voxel. In this study, modified spin echo phase contrast pulse sequences were used to map proton resonance line widths in phantoms and in vivo. In agar gels containing varying concentrations of Fe3O4 (magnetite), line broadening mechanisms permitted accurate spatial localization of iron deposits from measurement of local resonance line widths. Furthermore, line widths estimated from the data were strongly correlated with iron concentrations, indicating the potential quantitative applications of the method. The technique was applied clinically to map iron in subacute brain hemorrhages. These data suggest that resonance line widths may be a useful measure of brain iron content. PMID- 3351041 TI - Benefits of Gd-DTPA for MR imaging of intracranial abnormalities. AB - Forty patients with symptoms of intracranial disease were studied with magnetic resonance before and after intravenous injection of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). The T1- and T2-weighted images were obtained in all patients. Ninety brain lesions were found in 36 patients, including primary (20 patients) and metastatic (six) tumors, hemorrhage (one), progressive multifocal leukoencephalopathy (one), cysticercosis (one), infarction (four), and postoperative changes (four). Postcontrast images revealed lesions not seen on precontrast scans in eight (20%) patients. Also, the postcontrast images showed a change in appearance of the lesions in 20 (50%) that provided helpful information for assessing the abnormality in 20 cases (50%). Gadolinium-DTPA did not obscure any of the lesions seen on precontrast scans. It improved conspicuity, helped characterize and delineate the extent of lesions, and increased the sensitivity for detection of cerebral abnormalities. PMID- 3351042 TI - The MR contribution after CT demonstration of supratentorial mass effect without additional localising features. AB - The contribution of magnetic resonance (MR) imaging was retrospectively evaluated in 24 patients in whom CT demonstrated a supratentorial mass effect without significant additional localising features. Using a combination of T1-weighted inversion recovery (IR) and T2-weighted spin echo sequences, the MR images localised the lesion with greater precision than CT in 80% of cases. Areas of contrast enhancement were visible on the IR images in five of nine (56%) patients assessed after intravenous gadolinium-diethylenetriamine pentaacetic acid, where no comparable enhancement was seen on CT. Twenty of the 24 patients subsequently underwent surgery; eight had biopsies and 12 had resections. Magnetic resonance accurately predicted the site of the tumour in all these patients. Three of the remaining four cases were treated with radiotherapy on the basis of the MR findings without a tissue diagnosis being sought. Magnetic resonance produces better localization than CT and provides a sound basis for further diagnostic and therapeutic procedures. PMID- 3351043 TI - MR imaging of intracranial tuberculomas. AB - Eight patients with intracranial tuberculomas were studied with CT and magnetic resonance (MR) imaging. Large, ring enhancing, solid lesions on CT showed low intensity on T2-weighted images and intermediate intensity on T1-weighted images. Small lesions, with ring enhancement on CT, showed central bright signal on T2 weighted images with a peripheral low intensity rim surrounded by high intensity edema. The MR imaging features of the tuberculomas were found to be distinct from those of abscesses, metastases, and gliomas. PMID- 3351044 TI - Hemorrhagic intracranial retinoblastoma metastases: MR-pathology correlation. AB - Retinoblastoma is a highly curable tumor unless extraocular extension or metastases have occurred. Intracranial retinoblastoma metastases usually result from either contiguous or hematogenous spread and are rapidly fatal. We report two cases of pathologically proven, hemorrhagic intracranial retinoblastoma metastases and correlate magnetic resonance images with pathologic findings. Magnetic resonance with its high sensitivity and specificity for blood extravasation can document the associated hemorrhagic component of the tumor and help in the differentiation of nonmetastatic second neoplasms in retinoblastoma patients. PMID- 3351045 TI - Quantitative flow measurement in phase contrast MR angiography. AB - The quantitative nature of phase contrast magnetic resonance angiography is explored, and a technique of blood flow measurement that is independent of system and patient parameters is presented. Phantom and patient studies demonstrate that quantitative flow measurements by phase contrast angiography can be routinely obtained with good accuracy despite nonuniform sensitivity profiles, blood flow pulsatility, and patient-to-patient changes in system gain. The calibration method requires the acquisition of only two flow images and thus can be performed as part of an angiographic session. Flow calibration of any flow profile can be accomplished with this technique. The solutions for plug flow and parabolic flow are presented. PMID- 3351046 TI - CT detection of calcified nodal metastases of lung adenocarcinoma. AB - Computed tomography of a right middle lobe mass showed no evidence of calcification. Focal calcification in the right midhilar and subcarinal regions was presumed to be granulomatous. Thoracotomy revealed a partially psammomatous adenocarcinoma of lung and dense psammomatous deposits of adenocarcinoma in calcified regional lymph nodes. PMID- 3351047 TI - Metastatic choriocarcinoma simulating an arteriovenous malformation on chest radiography and dynamic CT. AB - A metastatic choriocarcinoma of the right lower lung simulated an arteriovenous malformation on chest radiography and dynamic CT. PMID- 3351048 TI - MR imaging of mediastinal pseudocyst. AB - Magnetic resonance imaging of a mediastinal pseudocyst clearly demonstrated the entirely intrathoracic location of the pseudocyst. PMID- 3351049 TI - Potential MR pitfall in relying on lesion/liver intensity ratio in presence of hepatic hemochromatosis. AB - We present a case of hepatic metastasis studied by magnetic resonance imaging in which a spuriously high lesion/liver intensity ratio (suggestive of cavernous hemangioma) was obtained due to underlying hemochromatosis. PMID- 3351050 TI - Hemiazygos continuation of a left inferior vena cava: CT appearance. AB - The CT appearance of hemiazygos continuation of a left-sided inferior vena cava is presented along with discussion of associated anomalies. PMID- 3351051 TI - Gadolinium-DTPA enhanced MR imaging of intravenous extension of adrenocortical carcinoma. AB - A case of magnetic resonance imaging of adrenocortical carcinoma extending into the inferior vena cava is presented. Magnetic resonance was able to outline the intraluminal extent of tumor thrombus accurately. Signal intensity ratios (mean 0.98 +/- 0.02) of tumor thrombus/primary tumor on T1- and T2-weighted sequences were useful for tissue characterization of tumor thrombus. Time course of the signal intensity of thrombus before and after intravenous administration of 0.1 mmol/kg gadolinium-diethylenetriamine pentaacetic acid was identical to the primary tumor which aided in differentiation from nontumor thrombus. PMID- 3351052 TI - Diagnosis of perirenal fibrosis by MR imaging. AB - A case of retroperitoneal perirenal fibrosis resulting in bilateral proximal ureteral obstruction is reported. Magnetic resonance imaging provided tissue specific diagnosis of the disease. PMID- 3351054 TI - Role of contrast enhancement in cerebral CT of carbon monoxide poisoning. AB - Postcontrast cerebral CT offers advantages as an adjunct to noncontrast CT in the evaluation of patients with carbon monoxide intoxication. It is of particular value when the noncontrast CT is normal with its ability to enhance otherwise isodense lesions. In this regard it can more accurately define the extent of the CNS insult and in some instances offer insight into the patient's eventual clinical outcome. Contrast medium was useful in this instance to more clearly elucidate typical injury to globus pallidus as well as rather unusual involvement of putamen. PMID- 3351053 TI - Brain malformations in linear nevus sebaceous syndrome: an MR study. AB - A case is presented of a 16-year-old girl who had unilateral linear nevus sebaceous syndrome and ipsilateral brain malformations. These consisted of unilateral megalencephaly, white matter hypoplasia and excessive gray matter, deficient sulcation, and focal areas of pachygyria of the frontal lobe best seen on magnetic resonance imaging. PMID- 3351055 TI - Eosinophilic granuloma of the spine: MR demonstration. AB - Eosinophilic granuloma commonly involves bone; however, neurologic deficit secondary to bony or extraosseous extension of disease of the spine is rare. We report a case of eosinophilic granuloma of the cervicothoracic junction in a 10 year-old boy and demonstrate the value of magnetic resonance imaging in defining the initial extent of the disease and following the resolution of the extraosseous involvement after therapeutic intervention. PMID- 3351056 TI - Pantopaque mimicking spinal lipoma: MR pitfall. AB - We present a patient with an intraspinal, high-signal-intensity lesion in the lumbosacral region on T1-weighted magnetic resonance images and a thin line of signal void between this region and the CSF on T2-weighted images. These findings were interpreted initially as representing an extradural spinal lipoma. However, CT revealed an intrathecal collection of iophendylate (Pantopaque), which was subsequently removed via a lumbar puncture. The apparent separation of Pantopaque from the CSF (seen on T2-weighted images and interpreted as the dura) was probably caused by chemical shift artifact, chemical shift contour, and/or CSF motion artifact. PMID- 3351057 TI - MR demonstration of bilateral intrathyroidal parathyroid glands. AB - A patient with hyperparathyroidism underwent magnetic resonance (MR) imaging and two intrathyroidal hyperplastic parathyroid glands were demonstrated. Surgery confirmed MR findings. PMID- 3351058 TI - CT diagnosis of celiac artery aneurysm. PMID- 3351059 TI - Clear cell basal cell epithelioma: light and electron microscopic study of an unusual variant. AB - We report the light and electron microscopic study of 7 examples of an unusual clear cell variant of basal cell epithelioma (BCE). The clear cells show cytoplasmic vacuoles that contain glycogen but do not stain with mucicarmine or fat stains. By electron microscopy the cytoplasmic vacuoles consist of empty spaces not surrounded by membranes. The clear cell pattern may occupy all or part of a given tumor. Typical nodular BCE was found in all 7 cases, but not in every section. Some nodules were composed of mixed solid and clear cell types. Differentiation of this uncommon variant from other clear cell tumors is important. PMID- 3351060 TI - Necrobiosis lipoidica diabeticorum with cholesterol clefts in the differential diagnosis of necrobiotic xanthogranuloma. AB - The histopathologic findings in 331 cases of necrobiosis lipoidica diabeticorum seen during a 50-year period were reviewed. Three cases showing cholesterol cleft formation were found. All 3 cases were associated with severe diabetes mellitus. The differential diagnosis of importance is necrobiotic xanthogranuloma. Common features included extensive hyaline necrobiosis and foreign-body giant cells. Atypical and Touton-type giant cells are more common in necrobiotic xanthogranuloma. Vascular changes in necrobiotic xanthogranuloma may include granulomatous involvement of muscular walls with thrombosis. Explanations for cholesterol cleft formation are offered. When cholesterol clefts are seen in biopsy specimens of necrobiosis, necrobiotic xanthogranuloma must be ruled out. In addition, when found in necrobiosis lipoidica diabeticorum, these clefts may imply diabetes mellitus with complications. PMID- 3351061 TI - Proliferation of eccrine sweat ducts associated with alopecia areata. AB - Proliferation of sweat ducts has been described as a reactive process in a variety of benign and malignant neoplasms and inflammatory conditions in the skin, including scarring alopecia. However, to our knowledge this phenomenon has not been observed in non-scarring alopecia. The following case documents such a proliferation arising in an alopecia consistent with alopecia areata. An 83-year old female developed progressive, fairly well circumscribed patches of alopecia over a 2-3 year period. Unequivocal scarring was not present. Histopathological examination revealed non-scarring alopecia with miniaturized and telogen follicles and a proliferation of eccrine ductal structures in the reticular dermis. These ductal structures varied in size and degree of cystic dilatation and resembled a primary eccrine neoplasm, such as syringoma. Only minimal focal fibrosis was observed in association with the eccrine proliferation. In summary, this case indicates that eccrine sweat duct proliferation may occur in non scarring alopecia and must be differentiated from a primary eccrine neoplasm. PMID- 3351062 TI - Eruptive vellus hair cyst and steatocystoma multiplex: two related conditions? AB - Eruptive vellus hair cyst and steatocystoma multiplex are infrequent lesions. Although there are clinical similarities between both entities, histologic features are distinctive. Especially noteworthy is the presence of sebaceous glands within the cyst wall of steatocystoma. We describe herein a patient with a familial monomorphous papular eruption on the forehead, biopsies from which showed features of both eruptive vellus hair cyst and steatocystoma multiplex. PMID- 3351063 TI - Ganglioneuromatous tumor of the skin: a combined heterotopia of ganglion cells and hamartomatous neuroma: report of a case. AB - We report the histologic and ultrastructural findings of a solitary, unusual cutaneous tumor in a 69-year-old woman. The tumor is characterized by many mature ganglion cells in the papillary dermis and fascicles of unmyelinated axons in the lower dermis. The lesion is ganglioneuromatous but differs from the other ganglioneuromas histologically in that the ganglion cells do not intermingle with the neuromatous elements. It may represent a combined heterotopia of ganglion cells and hamartomatous neuroma. The histologic differential diagnosis and the possible pathogenesis are discussed. PMID- 3351064 TI - Aerolar sebaceous hyperplasia: a new entity? PMID- 3351065 TI - Point: extensive scalp-lifting. PMID- 3351066 TI - Counterpoint: the risks of the bilateral lateral scalp reduction. PMID- 3351068 TI - Electrosurgery: high-frequency modalities. AB - The most popular form of electrosurgery used in cutaneous surgery involves the application of high voltage electromagnetic energy in the form of a damped sine wave. This form of current may be applied by electrofulguration, electrodesiccation, or electrocoagulation. The principles involved in the application of these three forms of electrosurgery are discussed. PMID- 3351067 TI - Lymphangioma circumscriptum: review and evaluation of carbon dioxide laser vaporization. AB - Three cases of the classical form of lymphangioma circumscriptum are described to illustrate the varied clinical manifestations of these lesions. The anatomy and physiology of cutaneous lymphangiomas are reviewed and their classification is clarified as a guide to their management. Treatment was sought by these patients in order to alleviate complaints of copious transudate of lymphatic fluid and chronic relapsing cellulitis. All three were treated with carbon dioxide laser vaporization with good to excellent cosmetic results and complete resolution of their symptoms. Carbon dioxide laser vaporization may be a useful alternative to frequently unsuccessful traditional surgical forms of therapy for selective cases of classical lymphangioma circumscriptum. PMID- 3351069 TI - The glabellar transposition "banner" flap. AB - The frontoglabellar skin has long served in reconstruction of certain nasal and canthal defects. The glabellar transposition "banner" flap is relatively simple and efficient. It can be designed either on a curved glabellar line or as a vertical midline closure, depending upon requirements and aesthetic variables. PMID- 3351070 TI - Circumcision: a review and a new technique. AB - Numerous techniques for circumcision have been described in the literature. They range from the dorsal slit incision, the squeeze technique using the Gomco clamp or Plastibell, the sleeve resection technique, and the guillotine technique. An alternative technique, which has not been previously described, is presented. PMID- 3351071 TI - Stump the experts. PMID- 3351072 TI - Merkel cell tumor of the thigh. AB - This case of a Merkel cell carcinoma is unusual due to the occurrence of the tumor on the thigh; most Merkel cell tumors have been found on the sun-exposed region of the head and neck. Histologically, the nodule was composed of sheets of uniform, poorly differentiated cells with a high nuclear to cytoplasmic ratio. Electron microscopy revealed perinuclear filaments, scattered dense core granules, and complex, interdigitating processes within cytoplasmic membranes. Treatment consisted of surgical excision of the tumor with a wide margin. PMID- 3351073 TI - The measurement of the volume of leg ulcers. AB - A method designed to measure the volume of cutaneous ulcers is described that utilizes a silicon rubber dental impression material. This technique is compared to the more popularly used computerized image analysis method in the determination of the size of cutaneous ulcers. PMID- 3351074 TI - Bilateral chondroma of the auricle. AB - Benign extraosseous cartilaginous lesions are uncommon and favor mainly the soft tissues of the hands and feet. We report a case of chondroma of both auricles. This localization has not been previously reported in the literature. PMID- 3351075 TI - Treatment of perichondritis with a quinolone derivative--norfloxacin. AB - Auricular perichondritis is an uncommon complication following surgery of the external ear. Pseudomonas aeruginosa is the most commonly associated pathogen. Presented is a patient with auricular perichondritis successfully treated with norfloxacin, a newly available, orally administered antibiotic with antipseudomonal activity. PMID- 3351076 TI - A caveat for use of skin flap templates. PMID- 3351077 TI - Nonmammalian safety tests for Lagenidium giganteum (Oomycetes: Lagenidiales). PMID- 3351078 TI - Mortality and developmental abnormalities induced by two juvenile hormone analogs on nymphal German cockroaches (Dictyoptera: Blattellidae). PMID- 3351079 TI - Toxic baiting of the Western yellowjacket (Hymenoptera: Vespidae) in Hawaii. PMID- 3351080 TI - Performance of insecticides for control of cat fleas (Siphonaptera: Pulicidae) indoors. PMID- 3351081 TI - Effect of trap placement on detection of Cochliomyia hominivorax (Diptera: Calliphoridae). PMID- 3351082 TI - Impact of cattle grub (Hypoderma spp.) (Diptera: Oestridae) infestations on performance of beef cattle. PMID- 3351083 TI - Arena test for evaluating chemical repellency in Blattella germanica (L.) (Orthoptera: Blattellidae). PMID- 3351084 TI - Vinyl plastic cage design for single-mating experiments to chemosterilize the stable fly (Diptera: Muscidae) with bisazir. PMID- 3351085 TI - Cyhexatin and fenbutatin-oxide resistance in Pacific spider mite (Acari: Tetranychidae): stability and mode of inheritance. PMID- 3351086 TI - Promotional strategies for ET nurses. PMID- 3351087 TI - The daring young man on the gurney. PMID- 3351090 TI - Urinary incontinence. Standards of care. International Association of Enterostomal Therapy. PMID- 3351088 TI - Into the future: research and the ET nurse. PMID- 3351089 TI - The impact of infectious diseases on health care providers. PMID- 3351091 TI - Life span growth and development: a review and application to nursing diagnosis. PMID- 3351092 TI - Management of fistula care with a wound drainage collector. PMID- 3351093 TI - An unusual challenge: oral-cutaneous fistula. PMID- 3351095 TI - [Changes in the mechanical stability of the erythrocytes and the morphobiochemical indices of the blood of cattle as affected by the genotype in ontogeny]. PMID- 3351094 TI - [The oxygen absorption process during phagocytosis by neutrophilic leukocytes in different mouse strains]. PMID- 3351097 TI - [DNA damage in the composition of cells and tissues]. PMID- 3351096 TI - [Induction of the beta and gamma states of the comuton regulation of mitochondrial oxidative phosphorylation by inorganic phosphate]. PMID- 3351098 TI - [Experimental evidence of the intracellular formation of ethanol and its role in the cell as an intermediate metabolite]. PMID- 3351099 TI - [Antibacterial activity of derivatives of alpha-amino-alkyl(aryl)phosphonic acids]. PMID- 3351100 TI - [Products of biphenyl catabolism by a Pseudomonas putida strain carrying the biodegradation plasmid pBS 241]. PMID- 3351101 TI - [Ferricyanide reduction by human erythrocytes in the presence of carriers of redox equivalents across the membrane]. PMID- 3351102 TI - [Correction of biochemical disorders in the lipid metabolism of atherosclerosis patients by using the antioxidant dibunol]. PMID- 3351103 TI - [Cellular composition of the spermatogenic epithelium in mice during and after exposure to permanent magnetic fields of various durations]. PMID- 3351104 TI - [Effect of radiation on metabolism in rodents]. PMID- 3351105 TI - Amnesia as a consequence of male rape: a case report. PMID- 3351106 TI - Comment on Berenbaum, Oltmanns, and Gottesman (1985): "Formal thought disorder in schizophrenics and their twins". PMID- 3351107 TI - Explanatory style change during cognitive therapy for unipolar depression. PMID- 3351108 TI - Negative cognition and the persistence of depression. PMID- 3351109 TI - Schizophrenia is associated with altered orienting activity; depression with electrodermal (cholinergic?) deficit and normal orienting response. PMID- 3351110 TI - Control and loss of control over eating: an experimental investigation. PMID- 3351111 TI - Attention deficit in schizophrenia and schizotypy: marker versus symptom variables. PMID- 3351112 TI - The influence of hypnosis on memory after one day and one week. PMID- 3351113 TI - Emotional information processing: modulation of fear in normal and dysthymic subjects. PMID- 3351114 TI - Impact of adolescent drug use and social support on problems of young adults: a longitudinal study. PMID- 3351115 TI - Dysfunctional attitudes are mood-state dependent. PMID- 3351116 TI - Psychophysiological assessment of anxious emotional states in children. PMID- 3351118 TI - An Expanded Attributional Style Questionnaire. PMID- 3351117 TI - Specificity of attributions and overgeneralization in depression and anxiety. PMID- 3351119 TI - Depression and the magnification of failure. PMID- 3351120 TI - Emotionality and mental health: longitudinal findings from the normative aging study. PMID- 3351121 TI - Left-handedness and though disorder in the schizophrenias. PMID- 3351122 TI - Latency of auditory brain-stem responses and otoacoustic emissions using tone burst stimuli. AB - A comparison of the latency of auditory brain-stem responses (ABR) and evoked otoacoustic emissions (EOAE) has led to an interpretation for the travel of transients in the peripheral auditory system that is consistent with both sets of data. The "cochlear echo" theory for the origin of the EOAE indicates that the latency of a particular frequency component back to the ear canal should be twice the forward latency of its characteristic place in the cochlea. The latency of wave V of the ABR to tone-burst stimuli can be described as the sum of two components: (1) a component that varies with intensity and frequency in an orderly and predictable manner and (2) a component that is independent of both intensity and frequency. Because the EOAE data can be predicted by taking twice the value of component (1) of the ABR latency, this component is interpreted to be due to mechanical travel through the cochlea. A consequence of this interpretation is that the remaining neural component of the ABR latency must be relatively independent of frequency and intensity. PMID- 3351123 TI - Comparison of electrophonic and auditory-nerve electroneural responses. AB - Electrophonic and auditory-nerve electroneural responses were recorded from the inferior colliculus of the cat. The electrophonic response appeared at a latency 1.0-1.5 ms later than the electroneural response, due to the time requirements for cochlear transduction. The electrophonic response also demonstrated very slow growth of response amplitude with increasing stimulus current as compared to the electroneural response. Aminoglycoside perfusion of the cochlea eliminated the electrophonic component from the evoked response record and left the electroneural component relatively unchanged, indicating that the electrophonic is an acoustic stimulus that requires an intact auditory end organ for transduction. PMID- 3351124 TI - Detection of complex echoes in noise by an echolocating dolphin. AB - Dolphins echolocate with short broadband acoustic signals that have good time resolution properties. Received echoes are often complex, with many resolvable highlights or components caused by reflection of the incident signal from external and internal boundaries of a target and from different propagational modes within a target. A series of experiments was performed to investigate how dolphins perceive complex echoes. Echoes were produced by a microprocessor controlled electronic target simulator that captured each emitted click and retransmitted the signal back to the animal after an appropriate time delay. The use of this "phantom" target allowed for precise control of the number of highlights, the time separation between highlights, and the relative amplitudes of highlights in the simulated echoes. An echolocating dolphin was trained to perform a target detection task in the presence of masking noise using these phantom echoes. The properties of simulated echoes were systematically varied, and corresponding shifts in the dolphin's detection threshold were observed, allowing for inferences of how the dolphin perceived echoes. The dolphin performed like an energy detector with an integration time of approximately 264 microseconds. PMID- 3351125 TI - Reference thresholds for the ER-3A insert earphone. AB - Several recent studies have demonstrated that the ER-3A insert earphone may sometimes be directly substituted, without recalibrating, for a TDH-39/MX-41AR earphone. However, most available data have not been reduced to a form suitable for establishing a revised estimate of the reference threshold levels. This article reports such a data analysis performed on the results of five recent studies. The mean data from the five studies are typically within 1 dB of the provisional reference threshold SPLs given by the ER-3A manufacturer for calibration in a (HA-1) 2-cc coupler. After converting the mean data to equivalent Zwislocki-coupler-type ear simulator SPLs at each of the reported audiometric frequencies (125, 250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz), agreement within 1.5 dB was seen with the revised estimate of minimum audible pressures given by Killion [J. Acoust. Soc. Am. 63, 1501-1508 (1978)]. Either the manufacturer's provisional SPLs or the average results from this study may be used with little noticeable difference for most purposes. PMID- 3351126 TI - Comodulation masking release for multicomponent signals. AB - Detection of signals composed of one, two, or three pure-tone components was examined in comodulated and noncomodulated masking noises. The masking noise was either a single 30-Hz-wide narrow band of noise, two narrow bands of noise, or three narrow bands of noise. Comodulation masking release (CMR) was greatest when (1) the signal was a single pure tone; (2) the masker was composed of three noise bands (as opposed to two); and (3) at least one flanking band was lower in frequency than the signal. Substantial CMRs did occur, however, for two- and three-component signals presented in two- and three-component maskers, respectively. The results of the present experiments did not support a "dip listening" hypothesis, nor models based strictly on across-frequency differences in stimulus envelope pattern or correlation. The results were more consistent with a model of CMR in which across-frequency envelope difference is coded by subtracting the envelope at the signal frequency from the envelope at a flanking frequency. PMID- 3351127 TI - Dichotic fusion of two tones one octave apart: evidence for internal octave templates. AB - Stimuli consisting of two simultaneous and sinusoidally frequency-modulated pure tones were dichotically presented to four listeners. Two component tones of each stimulus were approximately an octave apart. They were both modulated at 2 Hz, and the frequency swing resulting from each modulation corresponded to one tenth of the carrier frequency. The listeners' task was to detect phase differences between the modulation waveforms of the two simultaneous tones: With an adaptive 2IFC procedure, just-noticeable values of phi, the phase angle of the modulation waveforms, were measured as a function of the interval formed by the carrier frequencies (one octave, i.e., 1200 cents, +/- 0, 25, 50, or 100 cents). When the carrier frequencies were not too high, just-noticeable values of phi often varied nonmonotonically with the interval, showing a minimum at or near 1200 cents. An additional experiment indicated that most, if not all, of these octave effects were not due to some form of beat detection. As a whole, the results reported here provide evidence for the existence of internal octave templates. Such templates might play an important role in the perceptual segregation of simultaneous harmonic signals, as well as in pitch perception. PMID- 3351128 TI - An aeroacoustic approach to phonation. AB - A fluid mechanical, or aeroacoustic, point of view is followed to study possible sources of sound during phonation. Concentration is on two features of the vocal tract during phonation: abrupt area change from the glottis to the vocal tract and the finite length of the vocal tract. With these features, a source of sound distinct from the volume velocity source can be identified and a preliminary account of its effect on the acoustic field given. This source of sound is an oscillating force resulting from an interaction of rotational fluid motion with itself. Because of the schematic nature of the geometry of the model used here, this source may be considerably modified in actual phonation. It is concluded that specification of volume velocity is not enough to specify the source during phonation, even neglecting source-tract interaction. PMID- 3351129 TI - The effect of laryngeal nerve stimulation on phonation: a glottographic study using an in vivo canine model. AB - The present investigation was designed to examine the effect of change in vocal fold mass and stiffness on vocal fold vibration. To do this, the effect of variation in superior laryngeal nerve stimulation (SLNS) and recurrent laryngeal nerve stimulation (RLNS) was studied Photoglottography (PGG), electroglottography (EGG), and subglottic pressure (Psub) were measured in seven mongrel dogs using an in vivo canine model of phonation. The PGG, EGG, and Psub signals were examined at three frequencies (100, 130, and 160 Hz) for SLNS and RLNS, using a constant rate of air flow. Increasing SLNS, which caused a contraction of the cricothyroid muscle, produced a marked increase in F0, little change in Psub, an increase in open quotient (OQ), and a decrease in the closed quotient (CQ) of the glottal cycle. Increasing RLNS, which caused activation of the intrinsic laryngeal muscles, produced a modest increase in F0, a marked increase in Psub, no change in the OQ, and an increase in CQ. Phase quotient (Qp), which describes the interval between opening of the lower and upper fold margins, decreased with increasing RLNS and did not change significantly with increasing SLNS. Based upon changes in F0, Psub, OQ, CQ, and Qp, SLNS provides a physiologic correlate of the tension parameter Q, and RLNS provides a physiologic correlate of the parameter Psub in the Ishizaka and Flanagan two-mass model. PMID- 3351130 TI - Measuring the rate of change of voice fundamental frequency in fluent speech during mental depression. AB - A method of measuring the rate of change of fundamental frequency has been developed in an effort to find acoustic voice parameters that could be useful in psychiatric research. A minicomputer program was used to extract seven parameters from the fundamental frequency contour of tape-recorded speech samples: (1) the average rate of change of the fundamental frequency and (2) its standard deviation, (3) the absolute rate of fundamental frequency change, (4) the total reading time, (5) the percent pause time of the total reading time, (6) the mean, and (7) the standard deviation of the fundamental frequency distribution. The method is demonstrated on (a) a material consisting of synthetic speech and (b) voice recordings of depressed patients who were examined during depression and after improvement. PMID- 3351131 TI - Imitation of a VOT continuum by native speakers of English and Spanish: evidence for phonetic category formation. AB - This study examined imitation of a voice onset time (VOT) continuum ranging from/da/to/ta/by by subjects differing in age and/or linguistic experience. The subjects did not reproduce the incremental increases in VOT linearly, but instead showed abrupt shifts in VOT between two or three VOT response "modes." The location of the response shifts occurred at the same location as phoneme boundaries obtained in a previous identification experiment. This supports the view that the stimuli were categorized before being imitated. Children and adults who spoke just Spanish generally produced only lead and short-lag VOT responses. English monolinguals tended to produce stops with only short-lag and long-lag VOT values. The native Spanish adults and children who spoke English, on the other hand, produced stops with VOT values falling into all three model VOT ranges. This was interpreted to mean that they had established a phonetic category [th] with which to implement the voiceless aspirated realizations of /t/ in English. Their inability to produce English /p,t,k/ with the same values as native speakers of English must therefore be attributed to the information specified in their new English phonetic categories (which might be incorrect as the result of exposure to Spanish-accented English), to partially formed phonetic realization rules, or both. PMID- 3351132 TI - Intraspeaker variability in fundamental frequency stability: an age-related phenomenon? AB - The purpose of this investigation was to gather information on the extent to which intraspeaker variability on measures of jitter (%) and fundamental frequency standard deviation (F0 s.d.) is age related in women. Fifteen repeat productions of the vowels /i/, /a/, and /u/ from 22 young women (18-22 years) were analyzed for F0 s.d. and jitter. Findings for these young speakers were compared with those for elderly speakers tested previously (Linville and Korabic, 1987). Results indicate that the aging process brings about increases in the variability individual women demonstrate on measures of F0 stability when producing sustained vowels as steadily as possible. Further, young speakers differed markedly from elderly speakers in the pattern of frequency instability variations observed across the three vowels tested. PMID- 3351133 TI - Anisotropy of the ultrasonic backscatter of myocardial tissue: I. Theory and measurements in vitro. AB - This research addresses the variations in the ultrasonic backscatter from specimens consisting of a suspension of approximately aligned cylindrical scatterers in a fluid medium as a function of the angle of propagation in the sample. Predictions of the angular dependence of backscatter based on the time domain Born approximation described by Rose and Richardson [J. H. Rose and J. M. Richardson, J. Nondestr. Eval. 3, 45-53 (1982)] were compared with experimental measurements of the backscatter from both tissue-mimicking phantoms consisting of graphite fibers suspended in gelatin and from canine myocardial tissue. The angular dependence of the backscatter was predicted and measured to be maximum for propagation perpendicular to the cylinder axes and minimum for propagation parallel to the axes. Maximum to minimum (i.e., perpendicular to parallel) changes in the integrated backscatter were predicted to be between 5 and 10 dB in the phantom. The corresponding quantity measured in both the phantom and in canine myocardial tissue was approximately 6 dB. PMID- 3351134 TI - Anisotropy of the ultrasonic backscatter of myocardial tissue: II. Measurements in vivo. AB - The purpose of this investigation was to determine the angular dependence of the backscatter from canine myocardial tissue in vivo and to compare it with the variation of backscatter over the cardiac cycle that has been recognized and reported previously. The backscatter was measured from regions of left ventricular wall in canine hearts in which the fibers of the muscle lay parallel to the surface of the heart and were oriented predominantly in a circumferential fashion. Because of technical considerations, the angle of insonification was varied systematically through two cycles in which the angle relative to the muscle fiber axes ranged from 60 degrees-120 degrees. Backscatter was maximum at angles of interrogation perpendicular to the myocardial fibers and minimum at those most acute (60 degrees) relative to the orientation of the fibers. The previously observed variation of integrated backscatter over the heart cycle was evident at each angle of interrogation. At end systole, the average maximum-to minimum angular variation of integrated backscatter as 5.0 +/- 0.4 dB. At end diastole, the average maximum-to-minimum angular variation was 3.2 +/- 0.4 dB. Thus, even though angular dependence of the backscatter from tissues with directionally oriented structures is substantial, the anisotropy does not account for cardiac-cycle-dependent variation of backscatter. Accordingly, the angular dependence should be incorporated in approaches to quantitative tissue characterization with ultrasound. PMID- 3351135 TI - A technique for the study of acoustic scattering from microparticles. AB - A technique for observing acoustic scattering from individual particles with volumes on the order of 100 micron3 is described. The apparatus consists of an array of focused acoustic transducers, a fluid jet to position the particles, and electronics incorporating quadrature detection. A maximum likelihood estimator is developed for the scattering amplitude that combines the data received from a series of pulses as a particle is carried through the focal zone of the transducers. A calibration method and performance of the apparatus are discussed. PMID- 3351136 TI - Heterodyne interferometer for submicroscopic vibration measurements in the inner ear. AB - Conditions in the inner ear for interferometric measurements are quite different from those encountered in other mechanical systems: (i) The inner ear is not mechanically stable, due to blood pulsations and breathing artifacts; (ii) access to the inner ear is limited by anatomical constraints that make it difficult to visualize the structures of interest; (iii) vibration amplitudes to be measured in the inner ear are very low; (iv) the structures in the inner ear are nearly transparent; therefore, the reflectivity is low and attempts to change this reflectivity artificially usually alter the response characteristics; (v) cells are subject to light damage if the incident light intensity is too high, which limits the laser power that can be utilized in the interferometer. A heterodyne interferometer specially designed to measure vibrations in the living inner ear is described. Theoretical and experimental characteristics of this instrument are discussed in detail. In contrast to the homodyne system, the measurement accuracy of this interferometer is not affected by the low-frequency animal movements. This system does not require attachment of a reference mirror to the animal, thereby providing an unobstructed view of the structure to be measured. It has a high linearity and dynamic range. Its vibration sensitivity is high (2.8 X 10( 13) m for 1-Hz bandwidth) even under the condition of low light reflectivity (0.02%), with 0.5-mW incident laser power. PMID- 3351138 TI - Evidence of high-frequency acoustic emissions from the white-beaked dolphin (Lagenorhynchus albirostris). AB - Recordings of the signals from a school of white-beaked dolphins show that the frequency of their acoustic emissions extends to at least 305 kHz. These signals were detected by a sector scanning sonar used as a passive listening device of high bearing and time resolution. The records contain three types of signal, one of high intensity, one of a variable high repetition rate, and another showing a time-varying effect. Acoustic signals radiated by dolphins have been recorded and studied over a long period of time by many investigators. The purpose of this letter is to report evidence that acoustic emissions from white-beaked dolphins have significant energy at frequencies around 305 kHz, about one octave higher than previously observed. The observations discussed here were made aboard the fisheries research vessel CLIONE in the Wellbank flat area of the southern North Sea on 13 June 1970 between 1040 and 1110 h. When the dolphin signals were observed, the transmitter of the sector-scanning sonar in use was turned off, and the system was utilized as a passive listening device of high bearing and time resolution. PMID- 3351137 TI - Maintenance of intraoral pressure during speech after maxillary resection. AB - Although structural defects such as cleft palate and severe anterior open bite alter vocal tract resistance, compensatory responses usually result in maintaining consonant pressures at an adequate level. The purpose of the present study was to determine if individuals with an acquired palatal defect spontaneously develop similar compensatory behaviors. The pressure-flow technique was used to measure aerodynamic variables associated with consonant production after surgery and obturation. Although intraoral pressures decreased considerably immediately after surgery, pressures were maintained at a mean level of 3.5-cm H2O. Respiratory volumes increased as much as fourfold without obturation and were normal with obturation. Voice-voiceless differences in air volumes among consonants were maintained even in the presence of the defect. These findings suggest that compensatory responses are directed toward maintaining an appropriate level of intraoral pressure for consonant production. PMID- 3351139 TI - Resurgence of coronary artery endarterectomy. PMID- 3351140 TI - Tuberculous pericarditis: ten year experience with a prospective protocol for diagnosis and treatment. AB - Thirteen patients with tuberculous pericarditis (12 men and 1 woman aged 13 to 70 years [mean 41]) were identified in a group of 294 patients consecutively admitted for primary acute pericardial disease. The diagnosis was made by the following studies: sputum culture (n = 4), culture of pericardial fluid obtained by pericardiocentesis (n = 3), histologic study and culture of pericardial biopsy (n = 3), lymph node biopsy (n = 2) and pleural biopsy (n = 1). Clinical presentation was remarkably variable: four patients had an acute, apparently self limited course, one had relapsing tamponade, four had tamponade effectively treated with pericardiocentesis and four had toxic symptoms with persistent fever. The interval from hospital admission to diagnosis ranged from 1 to 14 weeks (mean 5.2). Constrictive pericarditis developed in six patients and effusive-constrictive pericarditis in one; all seven required pericardiectomy 2 to 3.5 months after admission. No patient died. It is concluded that 1) tuberculous pericarditis has a variable clinical presentation and therefore it should be considered in the evaluation of all instances of pericarditis without a rapidly self-limited course; 2) the diagnosis should be based only on objective data obtained with a systematic study protocol; 3) early definitive diagnosis is still difficult to achieve; and 4) development of subacute constrictive pericarditis requiring pericardiectomy is common. PMID- 3351141 TI - Doppler echocardiographic determination of the pressure gradient in hypertrophic cardiomyopathy. AB - The continuous wave Doppler ultrasound signal across the left ventricular outflow tract in hypertrophic cardiomyopathy has a characteristic pattern that is in keeping with the dynamic nature of the pressure gradient in this condition. To determine the accuracy and reliability of the peak Doppler flow velocity signal for measuring the peak pressure gradient in this condition, 340 beats were analyzed from five consecutive patients studied with simultaneous continuous wave Doppler ultrasound and dual catheter pressure recordings across the left ventricular outflow tract. Each patient was studied at steady state and during physiologic and pharmacologic manipulations of the pressure gradient. Peak velocity and calculated peak gradient were determined by two independent observers who did not know the catheter measurements. In addition, 18 beats with well defined flow velocity envelopes were digitized for analysis of the magnitude, timing and contour of the instantaneous Doppler ultrasound and catheter gradients throughout systole. Peak catheter gradient in the 340 beats ranged from 12 to 245 mm Hg. The correlations between the Doppler-derived and catheter peak gradients were close (r = 0.96, SEE = 4 mm Hg for Observer 1 and r = 0.97, SEE = 11 mm Hg for Observer 2). Interobserver variability for measurement of peak flow velocity was small (mean +/- SD 0.16 +/- 0.15 m/s). An interobserver difference greater than 0.3 m/s occurred in 25 of the 340 beats analyzed. By retrospective analysis, this was due to contamination of the outflow tract signal by mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351142 TI - Combined first pass and equilibrium radionuclide cardiographic determination of stroke volume for quantitation of valvular regurgitation. AB - A new noninvasive procedure for quantitation of cardiac valve regurgitation was evaluated using a combination of first pass and gated equilibrium radionuclide cardiography in 38 subjects with and without cardiac valve disease. Left-sided cardiac catheterization was performed to determine the severity of mitral incompetence and aortic regurgitation semiquantitatively. In healthy subjects and in patients without valve disease, stroke volumes were nearly identical with the two methods and the correlation was high (r = 0.98 [p less than 0.001]). The mean regurgitation fraction was 13% in patients with mild mitral incompetence and 2+ aortic regurgitation, 37% in patients with moderate mitral incompetence and 3+ aortic regurgitation and 57% in patients with severe mitral incompetence and 4+ aortic regurgitation. These findings suggest that combined first pass and gated equilibrium radionuclide cardiography, being insensitive to intracardiac shunts and right-sided valve disorders, constitutes a valid noninvasive technique for quantitation of left-sided cardiac valve regurgitation. PMID- 3351143 TI - Identification and catheter ablation of a zone of slow conduction in the reentrant circuit of ventricular tachycardia in humans. AB - Three patients who had incessant ventricular tachycardia and in whom a zone of slow conduction was identified are presented. Each patient's tachycardia was refractory to multiple antiarrhythmic drugs and was being treated with amiodarone at the time of the electrophysiologic study. The ventricular tachycardia cycle length was 500 to 580 ms. In Patients 1 and 2, a single site at the posterolateral wall or low septum in the left ventricle was identified at which overdrive pacing during ventricular tachycardia resulted in ventricular capture with a stimulus to QRS interval of 280 to 400 ms and with little or no change in the configuration of the QRS complexes during pacing as compared with during ventricular tachycardia. In Patient 3, the same phenomenon was observed at two areas in the left ventricle: at the inferior wall, overdrive pacing during ventricular tachycardia resulted in a stimulus to QRS interval of 440 to 470 ms, whereas at the posterolateral wall, the stimulus to QRS interval was 320 to 360 ms. Transcatheter shocks of 100 to 240 J delivered at the pacing sites have been successful in preventing recurrences of ventricular tachycardia over a follow-up period of 10 to 11 months. These observations may be explained by the pacing site being located within a reentrant circuit in a zone of slow conduction bounded by inexcitable tissue between the pacing site and the exit site of the reentrant circuit. In Patient 3, the variable stimulus to QRS intervals are explained by variable proximity of the pacing sites within the slow conduction zone to the exit site of the reentrant circuit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351144 TI - Endocardial mapping of ventricular tachycardia in the intact human ventricle: evidence for reentrant mechanisms. AB - A balloon array of 112 electrodes was used to obtain simultaneous recordings of endocardial electrograms during intraoperative mapping studies of ventricular tachycardia. Introduction of the balloon through a left atriotomy and across the mitral valve allowed endocardial activation maps to be obtained in the intact left ventricle. Of 20 patients with coronary artery disease studied in this way, suggestive evidence of endocardial reentry was found in 6. Three separate reentrant mechanisms were observed. In two patients, a single broad wave front of continuous recirculating activation reminiscent of a vortex was initiated by the formation of a functional arc of block in response to premature stimuli. In five patients, premature stimuli again produced a functional arc of block, which was circumvented by two opposing wave fronts that united on the distal side. Retrograde penetration by a narrow isthmus of slow conduction through the block initiated the tachycardia, whose activation sequence was consistent with figure eight reentry. In one patient, premature stimuli produced a region of delayed potentials. Critical timing of these resulted in microreentry in an adjacent circumscribed site, which formed the site of origin of the ensuing tachycardia. The microreentrant signals were not detected by standard unipolar recordings, but were seen on simultaneously recorded high gain electrograms. In 14 patients, although mapping identified a site of origin, the activation patterns showed either radial spread or incomplete circles. Detection of reentrant mechanisms during intraoperative mapping required high density electrode arrays and refined high gain recordings. An intact ventricle may facilitate intraoperative initiation of tachycardia. PMID- 3351145 TI - Prevalent myocarditis at necropsy in the acquired immunodeficiency syndrome. AB - The prevalence of myocarditis was retrospectively evaluated in 71 consecutive necropsy patients who died from acquired immunodeficiency syndrome (AIDS) between 1982 and 1986. Myocarditis was found in 37 cases (52%). Biventricular dilation at necropsy was present in seven cases (10%) and was accompanied by myocarditis in each case; fatal congestive heart failure occurred in four of these seven cases. Although viral, protozoan, bacterial, fungal and mycobacterial opportunistic pathogens were present in myocardial sections of 7 of 37 myocarditis cases, the etiology of myocarditis in the majority of these patients with AIDS remained idiopathic. Thus, myocarditis is a frequent finding at necropsy in patients with AIDS and may contribute to the development of biventricular dilation. PMID- 3351146 TI - Measurement of left atrial systolic time intervals in hypertensive patients using Doppler echocardiography: relation to fourth heart sound and left ventricular wall thickness. AB - The concept of left atrial systolic time intervals and Doppler echocardiography were used in a quantitative assessment of left atrial function in relation to the presence or absence of a fourth heart sound and to left ventricular hypertrophy in 47 patients with hypertension. Left atrial systolic time interval indexes included atrial pre-ejection period (the time between the onset of an electrocardiographic P wave and the onset of left ventricular inflow during atrial systole [A wave]), corrected atrial pre-ejection period (the atrial pre ejection period divided by the duration of the P wave), and atrial ejection time (the time between the onset and cessation of the A wave). Twenty-one patients with a fourth heart sound on the phonocardiogram had a shorter atrial pre ejection period (81 +/- 10 versus 89 +/- 14 ms p less than 0.05) and a corrected atrial pre-ejection period (66 +/- 17 versus 83 +/- 18 ms, p less than 0.01), as well as a longer atrial ejection time (147 +/- 15 versus 126 +/- 13 ms, p less than 0.001) than did 26 patients without a fourth heart sound. The ratio of atrial pre-ejection period to atrial ejection time and that of corrected atrial pre-ejection period to atrial ejection time was smaller in patients with than in patients without a fourth heart sound (0.56 +/- 0.08 versus 0.71 +/- 0.11, p less than 0.001; 0.46 +/- 0.16 ms-1 versus 0.67 +/- 0.17 ms-1, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351147 TI - Atrial signal variations and pacemaker malsensing during exercise: a study in the time and frequency domain. AB - To give some explanation for atrial malsensing in dual chamber pacing that occurs only during exercise, atrial electrograms from 33 patients were telemetrically recorded and analyzed in both the time and frequency domains. During exercise, an overall decrease from 6.4 +/- 1.9 to 5.6 +/- 1.9 mV (-11%) in the atrial signal amplitude was noted. Despite considerable variability among patients, marked changes occurred in 15 patients whose signals diminished by 11 to 49%. Slew rates showed a similar decrease from 1.35 +/- 0.45 to 1.18 +/- 0.45 V/s (-10.8%), with individual changes of as much as -51%. Signal attenuation in the time domain correlated well with frequency data, exhibiting a highly significant reduction of signal energy between 25 and 105 Hz. However, spectral distribution changed from rest to exercise, with a relative increase of signal energy in the range between 5 and 25 Hz and a decrease at higher frequencies. Individual changes differed widely when low (15 to 65 Hz) and high (65 to 115 Hz) frequencies were compared, but in a group of 11 patients signal attenuation in the high frequency band was more pronounced (-45%) than in the low frequency band (-23%). The clinical impact of the change in frequency distribution during ergometry was visualized by computer simulation of two different (low and high bandpass) filters. Although in individual patients, both characteristics may be favorable with respect to atrial sensing, it was observed in 11 patients that high pass filtering attenuates signal amplitudes by 10 to 24% in excess of the variation without filtering.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351148 TI - Percutaneous transluminal balloon valvuloplasty of congenital pulmonary valve stenosis, with a special report on infants and neonates. AB - Fifty-six percutaneous transluminal balloon valvuloplasty procedures were performed in 51 patients suffering from congenital pulmonary valve stenosis. The patients ranged in age from 1 day to 60 years (mean 6.9 years); 21 were infants less than 1 year of age, including 8 neonates. The peak systolic pressure gradient was greater than 50 mm Hg (mean 81.5) in 47 cases, and less than 50 mm Hg (mean 34.6) in 9. Valvuloplasty enabled a reduction in the mean right ventricular peak systolic pressure from 93.1 to 51.6 mm Hg (p less than 0.001), the mean transvalvular gradient from 73.4 to 27.0 mm Hg (p less than 0.001) and the mean right ventricular pressure expressed as a percent of systemic pressure from 99.5 to 52.0% (p less than 0.001). In infants and neonates, the mean right ventricular pressure expressed as a percent of systemic pressure decreased from 117.3 to 64.4% (p less than 0.001). In 23 patients, follow-up cardiac catheterization at 1 to 17 months revealed a significant change in the right ventricular systolic pressure, which decreased from 54.0 to 46.7 mm Hg (p less than 0.05), and in the peak systolic pressure gradient, which decreased from 27.3 to 22.6 mm Hg (p less than 0.05). Valvuloplasty is an effective procedure in relieving pulmonary stenosis in patients of all ages, including neonates. PMID- 3351149 TI - Balloon dilation of critical pulmonary stenosis in the first week of life. AB - Although balloon dilation of valvular pulmonary stenosis is established in infants and children, the techniques for and results of balloon dilation in neonates with critical pulmonary stenosis remain largely unreported. Since January 1, 1985, six successive neonates with critical pulmonary stenosis (aged 1 to 6 days) underwent attempted balloon dilation. Each was cyanotic and three of the six were on prostaglandin E1 therapy and three required tracheal intubation and ventilation. All had suprasystemic right ventricular pressures (mean 122.8 +/ 6.8 mm Hg). After hemodynamic evaluation and right ventricular angiography, the valve was crossed in five patients, and was first dilated with a low profile, 5 or 6 mm diameter, 2 cm long balloon. At least one more balloon was used in each patient, the largest being 95 to 133% of the diameter of the pulmonary valve anulus. The anulus size was 6.8 +/- 1.1 mm and the largest balloon size used was 6 to 10 mm. Right ventricular pressure decreased to nearly systemic level or less in five of five patients (58.8 +/- 6.7 mm Hg). Pressure gradients, measured in four infants, were 7, 12, 16 and 35 mm Hg, respectively, but were unreliable indicators of obstruction because of a patent ductus arteriosus. The five patients were discharged 3 to 8 days after balloon dilation. All are currently symptom free 10.6 +/- 11.7 months later, and all but one are believed clinically to have mild obstruction. Complications included iliac vein occlusion (n = 1) and complete right bundle branch block (n = 1). Although follow-up has been brief, neonates with critical pulmonary stenosis can safely undergo balloon dilation, usually with good short-term results. PMID- 3351150 TI - Determination of pulmonary to systemic blood flow ratio in children by a simplified Doppler echocardiographic method. AB - Doppler echocardiographic determination of the pulmonary to systemic blood flow (Qp/Qs) ratio requires calculation of pulmonary artery and aortic luminal areas and integrals of the Doppler systolic velocity curves. To simplify the Doppler calculation of the Qp/Qs ratio, the square of the ratio of pulmonary to aortic luminal diameters, substituted for the ratio of vessel areas, was multiplied by the ratio of pulmonary to aortic peak flow velocities, substituted for the ratio of velocity time integrals. The Qp/Qs ratios were calculated by both the conventional and the simplified Doppler method in 42 children, 1 month to 16 years of age. Fifteen children had no evidence of shunt and 27 had an intracardiac left to right shunt at the atrial or ventricular level, or both. In children with a shunt, the Qp/Qs ratio obtained at cardiac catheterization by oximetry ranged from 1.4:1 to 4.3:1. Both the conventional and the simplified Doppler Qp/Qs ratios correlated well with the oximetric Qp/Qs ratios (r = 0.94 and 0.93, respectively). Since the pulmonary to aortic luminal area ratio and velocity time integral ratio varied in each patient, neither measurement alone correlated well with the oximetric Qp/Qs ratio and, therefore, neither alone could be used as an estimate of the Qp/Qs ratio. The simplified Doppler calculation of the Qp/Qs ratio, which requires less time and no computer facilities, provides an excellent estimate of the Qp/Qs ratio in children. PMID- 3351151 TI - Spectrum of exercise intolerance in 45 patients with Ebstein's anomaly and observations on exercise tolerance in 11 patients after surgical repair. AB - To determine the effects of definitive operation for Ebstein's anomaly on rest and exercise cardiorespiratory function, cycle exercise studies were performed on 38 patients with Ebstein's anomaly before definitive operation and on 11 patients after operation. An atrial septal defect was present in 29 of the 38 preoperative patients and in none of the postoperative patients. Seven of the postoperative patients had tricuspid valvuloplasty and four had valve replacement. Exercise tolerance, as defined by maximal oxygen uptake, was significantly greater in patients after operation for Ebstein's anomaly than in the preoperative patients. However, exercise tolerance for preoperative patients without an atrial septal defect was similar to that for postoperative patients. Tricuspid valve repair or replacement appeared to affect favorably cardiac output response to exercise. Rest systemic arterial oxygen saturation increased from 88 to 95% and exercise saturation from 77 to 93% after operation. Rest ventilatory equivalent for oxygen decreased from 48 +/- 13 preoperatively to 37 +/- 6 postoperatively, and exercise ventilatory equivalent for oxygen decreased from 53 +/- 23 preoperatively to 38 +/- 6 postoperatively. Definitive operation (tricuspid valvuloplasty or replacement and atrial septal defect closure) for Ebstein's anomaly results in significant improvement of exercise tolerance, normalization of systemic arterial oxygen saturation and reduction of excess ventilation at rest and during exercise. PMID- 3351152 TI - Regional distribution of cardiac output at rest and during exercise in patients with exertional angina pectoris before and after nifedipine therapy. AB - The short-term effects of sublingual nifedipine (20 mg) on cardiac output and its distribution at rest and during exercise were evaluated by measurement of iliofemoral blood flow and cardiac output in 10 men with stable angina pectoris controlled by metoprolol. At rest, nifedipine significantly decreased iliofemoral vascular resistance from 294 +/- 36 to 165 +/- 29 dynes.s.cm-5.10(2) (p less than 0.01) and significantly increased iliofemoral blood flow from 0.34 +/- 0.04 to 0.57 +/- 0.11 liters/min (p less than 0.05). Systemic vascular resistance was reduced from 19 +/- 1 to 13 +/- 1 dynes.s.cm-5.10(2) (p less than 0.001) and cardiac output increased significantly from 4.7 +/- 0.3 to 5.8 +/- 0.5 liters/min (p less than 0.05). Mean arterial pressure decreased significantly and heart rate increased significantly. During maximal upright bicycle exercise during nifedipine therapy, iliofemoral vascular resistance and leg blood flow were unchanged compared with control (23 +/- 2 versus 21 +/- 3 dynes.s.cm-5.10(2) and 4.7 +/- 0.5 versus 4.4 +/- 0.6 liters/min), cardiac output remained significantly increased (12.8 +/- 0.8 to 15.2 +/- 1.2 liters/min, p less than 0.05) and systemic vascular resistance remained significantly reduced (8 +/- 1 to 5 +/- 1 dynes.s.cm-5.10(2); p less than 0.001). The proportion of cardiac output distributed to the working lower limbs was significantly reduced at all exercise levels. In summary, nifedipine caused a redistribution of cardiac output by vasodilating nonexercising vascular beds without altering the locally mediated vasodilation in exercising muscle. In patients with coronary artery disease given nifedipine therapy, an increase in exercise tolerance is due to relief of myocardial ischemia rather than to increased peripheral oxygen delivery. PMID- 3351153 TI - Indecainide for treatment of ventricular ectopic depolarizations: efficacy, pharmacokinetics, hemodynamic effects and safety. AB - Ten patients were treated with oral indecainide for frequent ventricular ectopic depolarizations during a short-term, dose-ranging, single blind inpatient trial followed by open label long-term therapy for 2 years. During dose ranging, patients received placebo followed by 50, 75 and 100 mg of indecainide three times daily. Eight of the 10 patients achieved greater than or equal to 80% reduction in ventricular ectopic depolarizations during inpatient therapy. Mean ventricular ectopic depolarizations decreased from 15,792/24 h to 2,357/24 h on optimal dosage (p less than 0.01). Nine patients had paired ventricular ectopic depolarizations; four of the nine had greater than or equal to 99% reduction of these beats. Among seven patients with nonsustained ventricular tachycardia, five had 100% elimination of these events with indecainide and all had greater than or equal to 90% reduction in these events. Indecainide prolonged the PR interval 44 +/- 27 ms (p less than 0.0001) and the QRS interval 11 +/- 9 ms (p less than 0.0001) from baseline without prolongation of the QTc or JTc interval. The mean trough plasma level of indecainide on optimal dosage was 409 +/- 173 ng/ml and the mean plasma elimination half-life was 10.3 +/- 2.3 h (range 7.1 to 14.2). No adverse hemodynamic effects of indecainide were detected. Side effects during short-term therapy were mild and did not require discontinuation of the drug. Efficacy was maintained for some patients during long-term therapy for 2 years, although five patients discontinued therapy because of loss of efficacy or side effects. Indecainide is a highly effective and well tolerated antiarrhythmic drug for suppression of frequent and repetitive ventricular ectopic depolarizations. PMID- 3351154 TI - Quantitative assessment of left ventricular wall motion by two-dimensional echocardiography: validation during reversible ischemia in the conscious dog. AB - This study was designed to test the accuracy of echocardiographic radial shortening measurements during variable degrees of regional dysfunction produced by 14 transient (less than or equal to 10 min) coronary occlusions (8 left anterior descending coronary artery, 6 left circumflex coronary artery) followed by up to 24 h of reperfusion in chronically instrumented conscious dogs. Independent measurement of regional myocardial thickening was obtained using epicardial pulsed Doppler probes and served as a standard for comparison. Radial shortening fraction was derived from two-dimensional short-axis views along 12 equidistant radii. Six reference systems from the epicardial and endocardial centers of geometry (centroids) in a fixed or a floating position were explored. In the ischemic zone, percent thickening fraction averaged 22 +/- 5% at baseline, decreased to -4 +/- 4% during occlusion and gradually returned to baseline values after reperfusion. Percent change in radial shortening correlated significantly with percent change in thickening fraction in the ischemic zone. The worst correlation was seen with the floating endocardial centroid (r = 0.68), and the best was observed with the epicardial floating reference (r = 0.91). Moreover, the epicardial floating reference provided narrower 95% confidence limits of radial shortening and less heterogeneity among radii than did fixed reference systems. Thus, compared with an independent standard, echocardiographic measurement of radial shortening from the short axis provided recognition of discrete grades of regional dysfunction induced by transient reversible ischemia. This technique may be amenable for serial assessment of regional function after interventions on the ischemic myocardium. PMID- 3351155 TI - Modification of the centerline method for assessment of echocardiographic wall thickening and motion: a comparison with areas of risk. AB - The ability of the centerline method to discern regional myocardial risk area was evaluated using two-dimensional echocardiographic measurements and coronary artery occlusion in 16 open chest, anesthetized dogs. The centerline method was modified to allow determination of both wall thickening and wall motion at control and during coronary artery occlusion. End-systolic and end-diastolic echocardiographic images were analyzed at 100 equally spaced points around the centerline of the short-axis view of the left ventricle to determine shortening and thickening abnormalities. In vivo risk regions were assessed by microsphere injection during occlusion, and autoradiographic analysis revealed a mean (+/- SD) circumferential risk area of 37.5 +/- 7.7%. Abnormal function was established by three criteria on the basis of the control values for both fractional shortening and wall thickening: 1) less than 2 SD, 2) less than 95% tolerance limits, and 3) dyskinesia. The criterion of less than 2 SD estimated a risk area of 45.9 +/- 16.7% for fractional shortening and 37.2 +/- 16.8% for wall thickening. Although neither value was significantly different from the actual mean value for the risk region, the results for fractional shortening were greater than for wall thickening (p less than 0.01). The less than 95% tolerance limit method significantly underestimated risk area for both shortening (25.6 +/- 15.1%, p less than 0.05) and thickening (19.1 +/- 12.7%, p less than 0.001), as did analysis by dyskinesia (13.1 +/- 12.1% for shortening, p less than 0.001; 20.6 +/- 12.1% for thickening, p less than 0.01). Thus, modification of the centerline method allowed determination of both fractional shortening and wall thickening from echocardiographic images.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351156 TI - Cocaine-induced supersensitivity and arrhythmogenesis. AB - The mechanism of cocaine-related sudden death is unknown. To test whether cocaine potentiated changes in sinus cycle length, conduction in the atrioventricular node (AH interval) and ventricular effective refractory period induced by infused norepinephrine and ansae subclaviae stimulation, the dose-response curves of sinus cycle length, AH interval and ventricular effective refractory period to infused norepinephrine (0.01 to 0.20 micrograms/kg body weight per min) and the frequency-response curves to ansae subclaviae stimulation (1 to 4 Hz, 2 to 3 mA, 4 ms pulses) were determined before and after intravenous injection of cocaine (5 mg/kg) in 15 anesthetized open chest dogs. Cocaine potentiated shortening of sinus cycle length, AH interval and ventricular effective refractory period induced by norepinephrine infusion and shifted dose-response curves of these variables to the left in eight dogs (supersensitivity). Cocaine did not affect frequency-response curves of sinus cycle length and AH interval to ansae subclaviae stimulation. Ansae subclaviae stimulation shortened the ventricular effective refractory period more after cocaine injection, but frequency-response curves were not shifted to the left in seven dogs (no supersensitivity). Cocaine did not enhance electrical induction of ventricular tachyarrhythmias in 15 dogs without acute myocardial infarction. Acute myocardial infarction was produced by coronary artery ligation in another group of 21 dogs. Of 10 dogs with acute myocardial infarction, spontaneous or electrically induced ventricular tachycardia developed in 1 dog without drugs, in 3 dogs given norepinephrine and in 7 dogs given norepinephrine and cocaine (p less than 0.03 versus without drugs).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351157 TI - Electrophysiologic effects of a new antiarrhythmic agent, recainam, on isolated canine and rabbit myocardial fibers. AB - Recainam (Wy 42,362) is a new antiarrhythmic agent undergoing clinical evaluation, but its electrophysiologic effects in cardiac muscle are poorly defined. With microelectrode techniques, its profile in isolated preparations of dog and rabbit hearts was determined using drug concentrations of 10 to 300 microM. Recainam induced a concentration- and frequency-dependent decrease in the maximal rate of rise of the phase 0 of the action potential (Vmax), action potential amplitude and overshoot potential, with little or no change in the effective refractory period except in Purkinje fibers, in which it was markedly reduced. At a 300 microM concentration, Vmax was reduced 51% (p less than 0.001) in ventricular muscle and 44% (p less than 0.001) in atrial muscle, with no change in action potential duration or effective refractory period. At the same drug concentration in Purkinje fibers, Vmax was decreased by 41% (p less than 0.01), action potential duration at 90% repolarization by 36% (p less than 0.01) and effective refractory period by 34% (p less than 0.01). Recainam had no significant effect on the sinoatrial node, but it depressed phase 4 depolarization in isoproterenol-induced automaticity in Purkinje fibers. The drug had no effect on slow channel potentials induced by high concentrations of potassium and isoproterenol. The data indicate that the electrophysiologic profile of recainam in isolated cardiac muscle is consistent with the overall effects of class IC agents without having an effect on the slow calcium channel. Its major action is to depress Vmax, with little effect on refractoriness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351158 TI - Percent coronary stenosis: battered gold standard, pernicious relic or clinical practicality? PMID- 3351159 TI - Stimulation as a key to tachycardia localization and ablation. PMID- 3351160 TI - Sensitivity and specificity of invasive and noninvasive testing for risk of sudden death in Wolff-Parkinson-White syndrome. PMID- 3351161 TI - The chance encounter error. PMID- 3351162 TI - Forecasting menu-item demand in foodservice operations. AB - The state of the practice in forecasting menu-item demand in foodservice operations was determined. A survey to assess the forecasting techniques utilized by foodservice directors was administered to a random sample of 834 American Dietetic Association Members with Management Responsibilities in Health Care Delivery System. Statistical analysis of the 392 responses revealed that less than 25% of the practitioners were using mathematical models in forecasting menu item demand. Naive models were utilized by the majority of the respondents. The moving average technique was the most frequently used (14.8%) mathematical model. Approximately 75% of the practitioners indicated that continuing education is needed relative to the forecasting techniques that may be employed in foodservice management. PMID- 3351163 TI - Monitor of tray error rates for quality control. AB - Accuracy of tray assembly is essential for providing appropriate nutrition care to patients and maintaining patient satisfaction. A monitoring system of tray assembly error rates was designed to evaluate patient tray accuracy and to identify types of assembly errors. Data were collected during two morning, five noon, and five evening meals. Errors were classified according to type: omission, addition, or substitution. They were also classified by severity: error of convenience (not critical with respect to diet) or error of compliance (contradictory to diet order). Error rates were determined and compared by meal, weekday vs. weekend, and first half of assembly period vs. second half. An average error rate of 12.9% was calculated from the 6,553 trays studied, with error rates of 12.5%, 10.9%, and 15.1% for breakfast, lunch, and dinner, respectively. Evaluation of data revealed no significant difference in error rate as sorted by type of error, among meals, or between weekday and weekend. Only 2.7% of the trays had errors contradictory to the diet order. The error rate was significantly higher during the second half of the assembly period, and the highest error rates were observed for the evening meal. The methodology used in this study serves as the basis for quality control monitoring and as a motivational tool to stimulate improved performance by trayline employees. PMID- 3351164 TI - Daily physiological iron requirements in children. AB - Median daily iron absorption was determined in iron-replete males and females between 2 and 19 years of age from the upper and lower socioeconomic strata of the Venezuelan population. A comparison was made with iron absorption of well nourished children, on the basis of hematological and anthropometric reference values from the U.S. The median absorption level, which was calculated from the increase in total body iron due to growth and the daily losses through exfoliation and menstruation, was also used to estimate the requirements of 95% of the population. When the requirements were expressed in terms of body weight, no significant difference in iron absorption was observed between the three Venezuelan and one U.S. groups, ranging from about 30 to 38 micrograms/kg/day in both sexes between 4 and 16 years of age. However, when the requirements were expressed without division by the weight factor, the requirements of the better nourished groups were somewhat higher than those of the Venezuelan lower socioeconomic population with, in addition, a threefold variation over the 5 to 16 year age range. These findings suggest that the total iron requirements of children at a certain age may be most adequately expressed in terms of the optimal body weight for that age. PMID- 3351165 TI - Trace element status of children with PKU and normal children. AB - The trace mineral (chromium, copper, iron, selenium, and zinc) status of 10 children (4 to 13.8 years) with phenylketonuria (PKU) and 9 normal children (6.5 to 15.9 years) was assessed. The children with PKU were treated with a phenylalanine-free L-amino acid mix that supplied the following percentages (mean +/- standard deviation) of total daily intake: energy, 45 +/- 13; protein, 75 +/- 11; copper (Cu), 62 +/- 10; iron (Fe), 82 +/- 7; selenium (Se), 40 +/- 20; and zinc (Zn) 87 +/- 8. Diet records and blood samples were collected from each subject. Children with PKU had significantly greater mean intakes of Cu, Fe, and Zn than normal children. Mean serum Cu, Fe, and Zn concentrations of the children with PKU and normal children were not different despite significantly greater intakes by the children with PKU. Normal children had a significantly greater mean serum Se concentration and a mean blood chromium concentration 1.6 times that of children with PKU. Individuals whose primary source of protein is an elemental diet are especially at risk for multiple trace mineral deficiencies. Manufacturers of chemically defined medical foods should evaluate composition, specifically molar ratios between minerals, as a basis for product formulation. PMID- 3351166 TI - Caffeine intakes of children from a biracial population: the Bogalusa Heart Study. AB - To investigate caffeine intake patterns in children, dietary intakes were examined for a biracial sample of 1,284 infants and children. Twenty-four-hour dietary recalls were completed by parents of children aged 6 months and repeated at ages 1, 2, 3, and 4 years; children 10 years old served as their own respondents and were surveyed at ages 13, 15, and 17 years. The sample was 60% white and 40% black. Additional cohorts of 10-year-olds (no. = 686) were studied for temporal trend. Whites consumed significantly more caffeine than blacks as early as 1 year and persisted at a higher intake level from 2 to 17 years. This trend continued whether intake was measured in total milligrams, milligrams per 1,000 kcal, or milligrams per kilogram body weight. Significant sex differences in caffeine intakes per 1,000 kcal occurred among 15- and 17-year-olds (girls greater than boys). Peak periods of consumption occurred at ages 2, 3, 13, and 17. Snacks contributed large quantities of caffeine, particularly for 10-year olds. Most frequent sources of caffeine were regular carbonated beverages, chocolate-containing foods, and tea. Mean intakes of caffeine for 10-year-olds were consistent from 1973 to 1982. Those observations document caffeine intakes beginning early in life. PMID- 3351167 TI - Food chloride distribution in nature and its relation to sodium content. AB - Because of growing interest in the biological and clinical effects of dietary chloride as the anion accompanying the dietary cation sodium and because the standard food composition tables used in the United States to estimate sodium content do not contain data on chloride content, we analyzed the nutrient data base of the English workers Paul and Southgate, which contains an extensive listing of both chloride and sodium contents in foods. To examine food chloride distribution in nature, we focused on the uncooked, unadulterated, discrete, primitive foods in the data base (no. = 216 food items). The findings indicate the existence of both a large variability of chloride content among foods and a high degree of coupling of chloride with sodium. The contents of chloride and sodium varied over a similarly large range (coefficients of variation, 229% vs. 263%), differed very little from each other on the average (less than 20%), and correlated (r = 0.84, p less than 0.001) to the extent that greater than two thirds of the overall variation of chloride content was linked to that of sodium content. Those findings accord with the often posited but untested assertion that the chloride content of foods approximates and parallels that of sodium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351168 TI - Variables related to selection of conventional, cook-chill, and cook-freeze systems. AB - This article reports the use of various foodservice systems in hospitals of 300 beds or more and explores the relationship of system choice to hospital, city, and county size. The conventional system, which involves the production of food close to time of service, has been the traditional method of hospital foodservice for centuries. The technology of the 1960s initiated the use of alternative systems, such as cook-chill and cook-freeze. Data from a survey of 807 hospital foodservice directors indicate that the conventional system remains the primary choice for hospital foodservice, although an increasing number of hospitals are converting to the cook-chill system. Choice of foodservice system appears to be dependent on the size of the hospital, city, and county but did not differ by region across the United States. In general, the smaller the hospital, city, and county, the more likely the use of the conventional system. As size increases, so does the occurrence of alternative systems, with cook-chill systems being the primary alternative chosen. Additional information is needed on the comparative costs and cash flows of the various foodservice systems. PMID- 3351169 TI - Member characteristics, participation, and interests: Public Health Nutrition Practice Group. AB - A survey was developed to assess the level of participation and the membership interests of the Public Health Nutrition Practice Group (PHNPG). Forty-six percent (500 members) returned a completed survey. More than 80% of members believe PHNPG to be their main professional practice area "home" within the Council on Practice structure. Members overwhelmingly viewed practice group contributions as a responsibility, with personal career benefits being of secondary importance. Reading the practice group's newsletter and voting in elections were major areas of involvement. However, willingness to contribute time was a positive finding. Areas of interest and issues of greatest concern were identified. Results of the survey can be used to prepare long-range plans for PHNPG. Membership involvement in practice group activities is the key to an increase in re-enrollments and in new memberships. PMID- 3351171 TI - Tools to measure sensory appeal of menus planned for children. AB - The Menu Variety Checklist and Score Sheet is a tool to facilitate evaluation of sensory appeal. Comparisons made across evaluators and across menus show it to be more reliable and more readily diagnostic than subjective summary ratings. Although further research and development are needed to make it more precise and test its criterion validity, the checklist has sufficient advantages to make it a useful starting place or backup tool in research and clinical applications. PMID- 3351170 TI - Two-year follow-up of patients treated with a very-low-calorie diet and exercise training. PMID- 3351172 TI - Weight loss through dehydration in amateur wrestling. AB - The desire of the intense, highly competitive athlete to alter body weight without medical supervision commonly results in ineffective, hazardous, and counterproductive abuses that may often endanger health and may affect final growth potential in young wrestlers. Corrective nutrition practices are critical for the endurance athlete to train, compete, and avoid injuries effectively. The best preventive measure may be the education of wrestlers, parents, and coaches about the consequences of rapid and extreme weight loss and the significant role nutrition plays in successful training and competition for the endurance athlete, fluid replacement being a key concern. For as long as wrestlers are required to compete in different weight categories, the popular practice of competing at the lowest possible weight will probably continue. The best course of action nutrition professionals can take is to become acutely aware of the unique nutritional concerns of these athletes in order to make this practice as safe as possible. PMID- 3351173 TI - Age-related changes in regional cerebral blood flow and brain volume in healthy subjects. AB - Using the xenon-133 inhalation method, we studied the age-related decline in regional cerebral blood flow, calculated as the initial slope index (ISI), in neurologically normal subjects without any risk factors for cerebral arteriosclerosis (154 men and 123 women), ranging in age from 19 to 88 years. The decline in the ISI was rapid in younger age groups and gradual in older age groups. The ISI was higher in women than in men older than 40 years. Using computed tomography, we studied the age-related decline in brain volume index (BVI; 100% X brain volume/cranial cavity volume) in neurologically normal subjects without any risk factors for cerebral arteriosclerosis (92 men and 49 women), ranging in age from 37 to 86 years. The decline in the BVI was gradual in younger age groups and rapid in older age groups. The BVI was higher in women than in men older than 60 years. PMID- 3351174 TI - Alcohol use in a community-based sample of subjects aged 70 years and older. AB - The usual alcohol intake in a community-based sample of subjects aged 70 years and over was investigated. A sample of 825 subjects was drawn from the records of five general practices in a rural township and 774 subjects (93.8%) agreed to participate. A stratified sub-sample of subjects from the abstainers, infrequent, weekly, and daily drinkers was subsequently investigated in more detail. Men took alcohol more frequently than women and in greater quantities although frequency and amount decreased with age. The usual place for drinking was the home. The highest use of psychotropic drugs occurred in the abstainers, but this was significant for men only. When compared with drinking patterns in middle age, 60.1% of men and 30.3% of women said that they took less alcohol, while 7.4% of men and 11.1% of women said that they took more. The main reasons for decrease in alcohol intake were change in health and fewer social opportunities. The main reasons for increase in alcohol intake were more money and more time. Drinking was most commonly associated with social activities and few took alcohol to help cope with personal situations. PMID- 3351175 TI - A telephone support service to reduce medical care use among the elderly. AB - A randomized controlled trial was performed to determine whether a telephone support system could reduce the frequency of ambulatory physician encounters. A total of 182 elderly persons were enrolled in the study. The experimental group was regularly called by a public health nurse and could call the nurse every weekday during normal working hours. The control group received no intervention. A year later, the experimental group reported 7.40 ambulatory encounters with a physician (SD = 4.94) and the control group reported 8.61 encounters (SD = 6.85). The difference between the groups, after adjusting for various prognostic factors, was 1.20 (95% confidence interval, -0.84 to 3.24). Although the difference did not achieve statistical significance, the results suggest that telephone support may bring about a substantial decrease in medical care utilization. Further research assessing the cost-advantage ratio for this type of intervention is recommended. PMID- 3351177 TI - Decisions to leave home. PMID- 3351176 TI - Religious activities and attitudes of older adults in a geriatric assessment clinic. AB - Few studies have examined the prevalence, salience, and impact of religious beliefs, activities, and commitment among medical patients in later life. Surveys of the U.S. population aged 65 years and over reveal a high frequency of such beliefs and activities, which are reported to play a significant role in their lives. In this study, the religious beliefs, activities, and motivations of 106 consecutive patients (mean age 74.4 years) attending a geriatric outpatient clinic were examined. A high prevalence of orthodox Christian beliefs, religious community activity, private devotional activity, and intrinsic religious orientation was found. Levels of religious activity and intrinsic orientation were lower among patients with cancer, chronic anxiety, depressive symptoms, and those who smoked cigarettes or consumed moderate to large amounts of alcohol. Intrinsic religiosity was lower among men with hypertension. Patients with mild to moderate dementia tended to have higher levels of intrinsic religious orientation. The results of this study suggest that religion is a powerful cultural force in the lives of older medical patients and is integrally related to both mental and physical health. PMID- 3351178 TI - The Consensus Conference on Comprehensive Geriatric Assessment: a dialogue is the beginning of consensus. PMID- 3351179 TI - What about geriatric pathology? PMID- 3351180 TI - Antidepressant metabolism in the elderly. PMID- 3351182 TI - In reply to Birkett. PMID- 3351181 TI - Reply to Risse and Barnes: Pharmacologic treatment of agitation associated with dementia. PMID- 3351183 TI - Who decides which lens is best? PMID- 3351184 TI - Run where they ain't. PMID- 3351185 TI - Protection from harmful UV radiation by contact lenses. AB - Ultraviolet radiation (UVR) has been demonstrated to be harmful to the cornea, the lens and the retina. Recent research has indicated that, in addition to the epithelial trauma found in UVR-induced keratitis, the deeper corneal layers are also involved. Since trauma to keratocytes and endothelial cells can result in permanent damage or cell loss, it is imperative to protect eyes against excessive dosages of UVR. Standard hydrogel contact lenses (Vistamarc normal) and newly developed UV-filtering hydrogel lenses (Vistakon UV-BLOC) were fitted on five rabbits and compared in protection from harmful UVR (300 nm). The eyes that wore the UV-filtering lens maintained normal corneas; however, the eyes that wore the standard hydrogel lens showed pronounced epithelial, stromal and endothelial changes. We concluded that the UV-filtering lens effectively absorbed the hazardous UV radiation while the standard soft lens provided little protection. PMID- 3351186 TI - Optical design considerations for contact lens bifocals. AB - Primary concerns for designing conventional bifocal contact lens optics involve placement of sufficient representation of distance and near optical powers before the pupil and minimizing the presence of secondary images. Geometrical models and lens measurements are used to establish guidelines for predicting bifocal contact lens performance. Proportional optical zone representation, image jump, and power distribution are presented for the most commonly employed bifocal zone configurations. Adequate zone representation and effective lens power are shown to be quite sensitive to variation in pupil size and position. Strategies for optimizing lens performance in view of these effects are discussed. PMID- 3351187 TI - Potential range of clear vision in monovision. AB - A possible limitation for monovision contact lens treatment of presbyopia is that an intermediate correction cannot be incorporated into the prescription without compromising distance or near vision. A simple model using a standard prescription strategy for the add and a conservative estimate for the static depth of focus of the eye was used to predict the range of clear vision with monovision lenses. For adds up to 2D, little compromise in visual acuity was predicted for any gaze position. PMID- 3351188 TI - Determining appropriate cylinder correction with soft toric lenses. AB - Several authors have advocated reducing cylinder power when fitting soft toric lenses. One rationale for this reduction is the formation of a tear lens due to incomplete flexure. Using toric lenses of various thickness (0.06-0.14 mm), I was unable to demonstrate the existence of a tear lens under thin or standard thickness Hydron toric lenses. In the absence of such a tear lens, it seems reasonable to use the same cylinder power in a soft toric lens as would be used if prescribing spectacles. PMID- 3351189 TI - The Tangent Streak rigid gas permeable bifocal contact lens. AB - An in-office clinical investigation to determine the fitting success rate and frequency and reasons for lens performance failure was conducted, using the Tangent Streak, a new rigid gas permeable bifocal contact lens. The patient population consisted of 34 highly screened presbyopic patients qualifying for a translating bifocal lens. The results revealed nearly 60% of all eyes were fitted successfully with the first lens ordered and an additional 22.4% met success criteria after a second lens order, for a total of 82.1% success. The average number of lenses needed to attain success was calculated to be 1.8 lenses per eye. Analysis of reasons for lens reorder, and frequency and types of lens modification is also summarized, and provides added information regarding the "customized" nature of this specialty lens. PMID- 3351190 TI - The dangers of distilled water in contact lens maintenance. AB - The reports of serious corneal infection associated with hydrogel lens wear prompted us to explore the level of sterility of the distilled water used by lens wearers in our practice. Fifty patients supplied samples of their partially-used distilled water for testing. Of the samples, 12% were found to be contaminated. Five samples of previously unopened distilled water were tested and no growth was found. We recommend that patients do not use distilled water for the care of hydrogel contact lenses. Rather, sterile unit dose or multi-dose (aerosol) nonpreserved, or preserved salines can be used. PMID- 3351191 TI - Sympathetic control of antral and pyloric electrical activity in the rabbit. AB - The effects of section and stimulation of the sympathetic nerve trunk on gastric motility were investigated in conscious and decorticate rabbits. In conscious animals after section of the abdominal splanchnic nerve, rhythm of antral and pyloric bursts was enhanced, becoming more regular, and the period of arrest of the rhythmic bursts, which was usually observed at the end of inflation of the antrum in intact rabbits, was shortened to 33.6 +/- 4.0 s from 112.2 +/- 14.6 s observed before the sympathetic nerve transection. Adrenergic agonists, phenylephrine (100 micrograms/kg), clonidine (5 micrograms/kg) and salbutamol (1 mg/kg) inhibited antral and pyloric activity. In decorticate rabbits the major effect of stimulation of the peripheral or the central end of the thoracic sympathetic trunk was inhibition; this was seen both with the spontaneous and vagally induced e.m.g. activity of the antrum and pylorus. Inhibition induced by stimulation of sympathetic efferents was abolished by beta-blocking agents and that induced by stimulation of the sympathetic afferents disappeared after alpha adrenergic block. Significance of a dual control of the gastric motility by the sympathetic nerve was discussed. PMID- 3351192 TI - Gender difference in a subpopulation of rat superior cervical ganglion neurons. AB - The number of superior cervical ganglion (SCG) neurons is equivalent in males and females on the day of birth. By 15 days, after most of the normal neuron death has occurred, males have 20-30% more neurons than females; and this difference persists in the adult. The present study was undertaken to determine whether this difference exists uniformly throughout the ganglion, or only in a subpopulation of these neurons. To study subpopulations of SCG neurons, bilateral transection of the internal carotid nerve, the external carotid nerve, or both postganglionic nerves was performed on neonatal male and female Sprague-Dawley rats on the day of birth. Littermate sham operates served as controls. Numbers of neurons were counted in SCGs of animals on either postnatal day 4 or 15, before or after normal development of the SCG sex difference. At 4 days, the number of SCG neurons in sham-operated males had females were not different, while at 15 days, sham-operated males had more SCG neurons than did sham-operated females. The number of neurons remaining in the SCG following neonatal transection of the internal carotid nerve were not different in males and females at either 4 or 15 days postnatal. The number of SCG neurons remaining following neonatal transection of the external carotid nerve was greater in males than in females at both 4 and 15 days postnatal. It was concluded that the gender difference in survival of SCG neurons lies in neurons projecting through the internal carotid nerve. The number of neurons projecting out the external carotid nerve is equivalent in males and females. PMID- 3351193 TI - The effect of coronary artery occlusion on the cardiovascular response to an aversive stress. AB - The cardiovascular response to a controlled aversive stress was investigated both before and during acute myocardial ischemia. Classical aversive conditioning (a 30-s tone reinforced with a 1-s shock) served as the model of stress while anterior wall myocardial ischemia was induced by the occlusion (hydraulic occluder) of the left anterior descending coronary artery. The conditional response consisted of significant increases (P less than 0.01) in mean arterial pressure (AP, 13.8 +/- 1.9 mm Hg, 14.3%), left ventricular (LV) dP/dtmax (1300 +/ 324 mm Hg/s, 34.7%) and heart rate (HR, 44 +/- 4 beats/min, 46.8%). Mean coronary vascular resistance significantly (P less than 0.01) increased first (CVR, 0.52 +/- 0.18 mm Hg/ml/min, 17.2%), then decreased (0.77 +/- 0.14 mm Hg/ml/min, 25.5%). In contrast, during acute myocardial ischemia both the HR and d(LVP)/dtmax conditional response were significantly reduced (P less than 0.01) by 58 and 54%, respectively (HR, 20.7 +/- 3.8 beats/min, d(LVP)/dt, 756 +/- 226 mm Hg/s). In addition, the initial CVR increase was virtually eliminated (0.13 +/ 0.10 mm Hg/ml/min, 74.0% reduction) while the CVR decrease was significantly reduced (P less than 0.01) by 48% (0.40 +/- 0.15 mm Hg/ml/min) during the coronary occlusion. The mean AP response, however, was not affected by myocardial ischemia. The pre-conditional stimulus cardiovascular variables were similarly unaffected by the coronary artery occlusion. Thus, coronary artery occlusion attenuated both the coronary and cardiac response elicited by an aversive stress. The mechanism mediating this inhibition of the conditional response remains to be determined but may involve the activation of vagal depressor reflexes during the acute ischemia. PMID- 3351194 TI - Withdrawal of collaterals of sympathetic axons to the rat eye during postnatal development: the role of function. AB - Neurones in the superior cervical ganglion (SCG) of the rat can be retrogradely labelled by injection of Fast blue (FB) into the anterior eye chamber with the maximum number being labelled during the second postnatal week. In adult rats, however, many fewer neurones can be so labelled. In the present study, we have investigated whether this reduction may be due to the withdrawal of collaterals of neurones which project to the posterior eye compartments. For these experiments, we have used either one (FB) or two (FB and horseradish peroxidase (HRP)) retrogradely transported markers injected with a micropipette into the anterior or posterior (vitreous) parts of the eye in rats aged 14, 31 and greater than 50 days. Using FB, we have shown that in 14-day-old rats, 40% of the neurones which project to the eye have collaterals in anterior and posterior compartments while only 1% of neurones maintain dual projections in animals aged more than 7 weeks. Furthermore, there is a reduction in the total number of neurones projecting to the eye between 14 and 31 days postbirth. The presence of significantly greater numbers of cells with collaterals to both eye compartments in the young versus the adult rats has been confirmed using both FB and HRP as retrograde markers. The importance of function on the rearrangement of these projections was investigated by either rearing animals in the dark from the time of birth, or by sectioning the preganglionic nerve trunk to the SCG, soon after birth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351195 TI - Direct evidence for concomitant release of noradrenaline, adenosine 5' triphosphate and neuropeptide Y from sympathetic nerve supplying the guinea-pig vas deferens. AB - Concomitant release of noradrenaline (NA) (using tritium labelling), adenosine 5' triphosphate (ATP) (using the luciferin-luciferase firefly technique) and neuropeptide Y (using the enzyme-linked immunosorbant assay) during electrical stimulation of the guinea-pig vas deferens has been demonstrated. In addition it has been shown: (1) that release of NA and ATP is unaffected following selective desensitization of the P2 (ATP)-purinoceptor by alpha, beta-methylene ATP and (2) that total block of contractile responses of the vas deferens to nerve stimulation by a combination of prazosin and alpha, beta-methylene ATP does not reduce the release of NA and ATP. These results are consistent with the hypothesis that NA, ATP and neuropeptide Y are released as co-transmitters or modulators in sympathetic nerves supplying the vas deferens. PMID- 3351196 TI - Direct connections between the central nucleus of the amygdala and the nucleus of the solitary tract: an electrophysiological study in the rat. AB - Reciprocal connections between the central nucleus of the amygdala (CNA) and the nucleus of the solitary tract (NST) have been implied from anatomical studies in the rat and physiological studies in other species. Our work supports this conclusion in that microstimulation of the NST caused both antidromic and orthodromic activation of neurons in the CNA. The distribution of CNA neurons activated by NST stimulation suggests that the dorsomedial portion of the CNA provides input to the dorsal medulla while the ventrolateral CNA receives input from the NST. PMID- 3351197 TI - Focus: nursing diagnosis. Promoting independence. PMID- 3351198 TI - Focus: nursing diagnosis. Impaired physical mobility. PMID- 3351199 TI - Focus: nursing diagnosis. Impaired skin integrity. PMID- 3351200 TI - Focus: nursing diagnosis. Alterations in thought process. PMID- 3351201 TI - A challenge for the future. PMID- 3351202 TI - [In vitro fertilization. Analysis of results after the first 2 years' activity]. AB - 413 menstrual cycles were monitored in the first two years of the work of the In Vitro Fertilization Unit in La Pitie-Salpetriere. On-going pregnancies were achieved from the very first months of activity, with a level which stayed relatively constant in the first year. Technical changes were introduced and in particular a higher recovery rate of oocytes when ultrasound was used and above all when LH-RH analogues were used in the process of stimulation. It is this last point that seems to be the most interesting. In fact, when the results are examined there is a definite rise in the number of on-going pregnancies of which the level went up by 2.3 times as compared with using a classical protocol of Clomithene citrate and HMG. In the 153 cycles when D-Trp6 LH-RH was used, the percentage of on-going pregnancies was 13.7% for each cycle and 20% for embryo implants. Furthermore, it became possible to work out the dates for the patients and this appears to us essential as the numbers of couples attending increase. PMID- 3351203 TI - [Endometriosis and fertilization in vitro. Apropos of 40 cycles]. AB - The physiopathology and the role of endometriosis in infertility is still unclear. The use of in vitro fertilization (IVF) could be a good model for the understanding of etio-pathology and treatment when fecundity is desired. We compare results of IVF procedure in patients with endometriosis after ovulation induction with clomiphene-HMG (group 1) and Gn-Rh analog's short administration using regimen and HMG (group 2). Forty cycles have been conducted for 18 patients. Mean duration of infertility is 6.9 years and mean age of patients is 34.8 years. We observed no difference in terms of results of ovulation induction in Gr 1 or in Gr 2 compared with IVF patients without endometriosis and after the same treatment regimen, except a non significant decrease in the number of recovered oocytes. As for IVF patients without endometriosis, the use of Gn Rh analogs permits an improvement of results in terms of suppression of spontaneous premature LH surge, and increase of number of follicles and cleaved embryos. The fertilization and cleavage rates are not affected by the presence of endometriosis when compared to IVF patients without endometriosis. The number of recovered oocytes decreases with the severity of endometriosis (RAFS classification), but the pregnancy rate is not affected. Overall Third trimester pregnancy rate is 12.5% per induction cycle and 21.7% per embryo transfer. We may conclude that the presence of endometriosis does not affect the quality of the oocyte and is not a cause of exclusion in an IVF program. PMID- 3351204 TI - [Spontaneous myospherulosis developing at contact with a mature cystic dysembryoma of the ovary. Pathogenetic discussion apropos of a case diagnosed by laparoscopic biopsy]. AB - The author has reported a case of spontaneous myospherulosis which developed adjacent to a benign cystic ovarian teratoma which was discovered by routine ultrasound examination in a young patient admitted for spontaneous abortion. This ovarian cyst had not been aspirated before. This report demonstrates that myospherulosis can be induced spontaneously by necrosis of fatty tissues. Up to now, this lesion was considered iatrogenic. In this case, it resulted from a physical process similar to the emulsion phenomenon between intra-tissular free fatty materials and plasma. This process gives rise to sequestration of blood cells, in particular erythrocytes by free fatty materials with the formation of "bags of marbles". These saccular structures thus produce inflammatory changes with foreign body granuloma and pseudo-cystization. PMID- 3351205 TI - [Cancer and nipple discharge]. AB - The authors, in a retrospective study, have looked at the clinical and paraclinical parameters that suggest that a cancer may be present when there is a nipple discharge. By using logistic regression on these criteria a model has been able to be constructed with four variables (bloody discharge, and associated palpable tumour, a suspicious mammographic appearance and atypical or proliferating cells in cytology). The probability of a cancer being present varies between three per thousand when none of the four variables are present to 99.1% when all four are present. A first outline of the therapy that can be used is suggested. PMID- 3351206 TI - [Menorrhagia, metrorrhagia and the endometrium. Apropos of 300 cases]. AB - The authors report on the different aspects they have observed when they studied 300 case histories of patients who had a histological examination of the endometrium for menorrhagia or metrorrhagia. In 9.9% of the cases the endometrium was normal. In those cases there was an associated lesion particularly of the myometrium. Whatever the type of bleeding, the most common finding was hyperplasia. The authors emphasize that this can evolve to dysplasia (4% of their cases) and to carcinoma of the endometrium (3% of the cases). PMID- 3351207 TI - [Donor artificial insemination. Psychological survey of 830 couples]. AB - 830 couples who had asked for Artificial Insemination by Donor (AID) were questioned using separate questionnaires for the husband and for the wife. The questions were directed to the reactions that followed in succession to discovery of the sterility, the psychological conditions that led to choosing AID, their attitude as far as secrecy was concerned and finally their contribution to finding donors of sperm. Overall the husband-wife replies corresponded to one another. Frequently the reaction to the news that the man is sterile is a depressive one and to a lesser degree followed by troubles in sexual performance. The choice of AID is usually a decision of both members of the couple. Most couples express themselves as hesitant about adoption. Most of them said that secrecy about the procedure was an essential condition. It appears that, above all, male sterility had to be hidden from the circle in which they associated and from the child. It is this position as far as secrecy is concerned that makes it difficult for the couples to help in recruiting sperm donors. PMID- 3351208 TI - [Pregnancies occurring after a perinatal death. Preparation of a psychological risk index]. AB - The authors have interviewed 21 women who were attending the gynaecological and obstetrical service of the hospital for pregnancies occurring after a perinatal death. They show that anxiety is characteristic of these situations, but that the intensity of anxiety varies from woman to woman. They describe, after analysing the interviews, the different variations that can be found as these pregnancies progress according to the type of anxiety. By using a statistical analysis they can separate out the most important criteria and they can work out a method of illustrating a threshold which can easily be used by obstetricians in everyday practice. They suggest a method of handling the patients according to the level of anxiety found. PMID- 3351209 TI - Changes in fetal organ flow during intrauterine mechanical ventilation with or without oxygen. AB - To investigate whether the changes in circulation at birth are due to lung ventilation, changes in PaO2 or both we mechanically ventilated in utero the lungs of 10 fetal sheep (120-127 days of gestational age) five days after instrumentation under general anaesthesia. Electrocortical activity (ECoG), eye movements (EOG), electromyographic activity from diaphragm and posterior neck activity (EMG) and electrocardiogram (ECG) were recorded. Fetal catheters (artery and vein of the hindlimb, arteries of both forelimbs which in three occasions were advanced into the left ventricle, fetal trachea and amniotic cavity), and an endotracheal tube were placed. After recovery radioactive 15 mu microspheres (I125, Ce141, Sr85 and Sc46) were injected into the inferior vena cava or left ventricle during high voltage electrocortical activity before and after lung expansion with N2 and after expansion with O2 for two levels of PaO2. PaCO2 did not change. The percentage of spheres trapped in the lungs increased from 9.6% to 44% after expanding the lungs with N2 and to 90% when fetal PaO2 increased (P less than 0.001). Blood flow to different organs did not change during normoxic expansion but it decreased significantly to the brain (91 +/- 25 to 27 +/- 8 ml/min per 100g, [mean +/- SD]) placenta (160 +/- 57 to 54 +/- 33 ml/min/100g) and coronaries (239 +/- 91 to 117 +/- 60 ml/min per 100g) when PaO2 was increased. In conclusion fetal circulation responds to raised levels of PaO2 well before birth probably by a direct action of oxygen on the vessels. PMID- 3351210 TI - Tissue glycogen concentrations in hypophysectomized pig fetuses following infusion with cortisol. AB - The role of cortisol as a factor controlling the deposition of glycogen in the pig fetus was examined by infusing either a low dose (1 mg/day) or a high dose (3 mg/day) of cortisol into chronically-catheterized hypophysectomized fetal pigs for five days beginning on day 100-104 of gestation. After infusion, liver glycogen was significantly higher (P less than 0.05) and lung glycogen significantly lower (P less than 0.05) than in uninfused hypophysectomized litter mates although concentrations were significantly different from intact litter mates (P less than 0.05). Although skeletal and cardiac muscle content increased after infusion this difference was not significant. Changes in tissue glycogen content were similar for both the low and high rates of infusion. These observations indicate that exogenous cortisol alone is able to stimulate liver glycogen deposition and reverse the effect of hypophysectomy. Although other factors may be necessary for maximal response this suggests that cortisol is an important stimulant for liver glycogen deposition in the fetal pig. The effect of cortisol on muscle glycogen was equivocal suggesting that other hormones may play a more important role in this tissue. PMID- 3351211 TI - The actions of cortisol on fetal renal function. AB - Renal function was studied in 6 fetal sheep, aged 126-135 days, before and after 3 injection of 15 mg of cortisol given at intervals of 12 h. Cortisol caused a significant rise in both renal blood flow (P less than 0.05) and glomerular filtration rate (P less than 0.005), and in urine flow rate (P less than 0.02) but it did not consistently cause a natriuresis. The urinary pH was unchanged following cortisol treatment, but bicarbonate excretion increased. Urinary phosphate excretion was increased (P less than 0.005) because of a rise in filtered phosphate and a fall in phosphate reabsorption. The titratable acid excretion increased (P less than 0.005) but urinary ammonium excretion did not. The total amount of sodium reabsorbed increased after cortisol but the amount of sodium reabsorbed in the proximal tubule did not increase, so fractional reabsorption in the proximal tubule decreased from 61.7 +/- 4.1% to 47.3 +/- 4.2% (P = 0.01). The total amount of sodium reabsorbed in the distal tubule increased and distal fractional reabsorption increased from 33.3 +/- 2.4% to 47.3 +/- 4.2% (P less than 0.01). Cortisol may increase the capacity of the immature kidney to play a role in fluid and electrolyte homeostasis by increasing glomerular filtration rate and delivering more sodium and water to the distal nephron where the reabsorption of sodium and water can be modified independently and in accordance with need. PMID- 3351212 TI - Relative motion of selected carpal bones: a kinematic analysis of the normal wrist. AB - The relative motion of selected carpal bones and the radius was studied using five cadaver specimens labeled with metal markers to precisely quantitate their motions. Data was obtained by means of a combination of orthoradiography, sonic digitization, and computer analysis. We conclude that the wrist functions as two carpal rows with the distal row bones relatively tightly bound to one another and the proximal row bones less so but still moving together. Therefore, we theorize that the proximal row functions as a variable geometry intercalated segment between the distal row and the radius-triangular fibrocartilage. PMID- 3351213 TI - The intercalated tendon graft for treatment of extensor pollicis longus tendon rupture. AB - Twenty-one patients with ruptures of the extensor pollicis longus tendon were treated with a subcutaneously placed free tendon graft. The repair was performed a mean of 6 weeks after rupture, range from 1 to 21 weeks. Data was collected on 19 of these patients, with a mean follow-up of 30 months, range from 6 to 124 months. Near uniform satisfaction was reported. The mean loss of interphalangeal joint extension and flexion and combined metacarpophalangeal-interphalangeal joint motion was 6 degrees, 3 degrees, and 10 degrees, respectively. The mean loss of pinch strength was 7%. All patients were able to elevate their thumbs to the level of the palm. This is a simple, reliable, and effective procedure that avoids the use of an adjacent motor-tendon unit. Muscle contracture appears reversible and this procedure may be used successfully even when treatment has been delayed. PMID- 3351214 TI - Ulnocarpal abutment after wrist arthrodesis. AB - We report three patients aged from 22 to 34 years, in whom ulnocarpal abutment developed after wrist arthrodesis. Two were treated by excision of the triquetrum and one by excision of the pisiform. The three patients were seen after wrist fusion because of ulnar wrist pain on forearm rotation, which was relieved by excision of a carpal bone. Two patients had had wrist arthrodesis because of wrist pain resulting from degenerative arthritis and silicone synovitis resulting from silicone rubber replacement of the lunate as treatment for Kienbock's disease. One patient had had a wrist arthrodesis to treat degenerative arthritis after an intra-articular distal radius fracture. The arthrodeses were all done with an A. O. plate and iliac crest bone graft. One patient gained forearm rotation after the excision of the carpal bone and none of the patients lost rotation. The average follow-up was 16 months. PMID- 3351216 TI - Flashbacks after traumatic hand injuries: prognostic indicators. AB - Flashbacks of a traumatic hand injury may compromise a patient's rehabilitation process. This study examined the nature and significance of these flashbacks in a work-injured population. We also evaluated the ability of these patients to return to work at the site of the original injury. Sixty-one patients with work related, traumatic hand injuries received psychological evaluation and treatment. All patients experienced flashbacks. The following three types of flashbacks were identified: (1) a replaying of the events occurring just before the accident and continuing until the injury (replay flashbacks), (2) an image of the injured hand just after the trauma occurred (appraisal flashbacks), and (3) images in which an injury that was more severe than the one that actually occurred were perceived (projected flashbacks). Regardless of the result of injury, patients with replay flashbacks were the most likely to return to their former employment (95.2%) after only 4.8 1-hour sessions of psychotherapy for control of symptoms. Patients with a combination of appraisal and projected flashbacks were the least likely to return to work (10.3%), despite the fact they received an average of 13.1 1-hour sessions of psychotherapy. PMID- 3351215 TI - Intrinsic muscle advancement to treat chronic palmar instability of the metacarpophalangeal joint of the thumb. AB - Chronic palmar instability of the metacarpophalangeal joint of the thumb can result in a significant disability. Grasp, particularly pinch, is painful and weak because the thumb goes into hyperextension. Stabilization of the metacarpophalangeal joint can be achieved by distal advancement of the conjoined tendon of the abductor pollicis brevis and lateral fibers of the flexor pollicis brevis. PMID- 3351217 TI - Biomechanical and clinical evaluation of the expandable intramedullary fixation device. AB - The use of an expandable intramedullary device for internal fixation of metacarpal or phalangeal bones is described. The device is applicable to transverse fractures, short oblique fractures, or transverse osteotomies. The device consists of a cylindrical apparatus made of titanium that allows collapse in the circumferential diameter. It is introduced into the medullary canal in its collapsed state, and on release expands to its normal diameter in the canal with the fracture reduced over it. A biomechanical evaluation compared the stability of this device with other commonly employed fixation methods. A retrospective review is presented of the first 43 patients in whom the device was implanted. PMID- 3351218 TI - Fracture of the hamate hook. AB - Twenty-one cases of hamulus fracture are presented. Diagnosis depends on clinical acuity. The most common symptom is pain in the palm that is aggravated by grasp. Weakness of grasp and dorsal wrist pain are also common. Ulnar nerve paresthesia or weakness and mild carpal tunnel syndrome are frequently present. Tenderness directly over the hamulus is always present, and grip strength typically is diminished. Tenosynovitis, tendon fraying, or tendon rupture may be demonstrated in 25% of the cases and is not related to the use of steroids. Lateral trispiral tomography is clearly superior to the other diagnostic methods. Excision produced generally excellent results, particularly in patients with an athletic injury or with no associated additional injury. A nonathletic injury or the presence of associated trauma adversely affected results. Immediate immobilization of acute fractures may result in fracture healing and obviate operative intervention. Open reduction and internal fixation is feasible but offers little advantage over excision. PMID- 3351219 TI - Focal myositis in the hand. AB - Focal myositis is a rare, benign, pseudotumor of skeletal muscle that is usually seen as a steadily enlarging soft tissue tumor in an otherwise healthy patient. Focal involvement of muscle with severe myopathic and inflammatory changes characterize the histology. The natural course of this disorder is spontaneous regression. We report the case of a 7-year-old girl with focal myositis of the index lumbrical muscle. This is the first reported incidence of focal myositis that involves muscle of the hand. PMID- 3351220 TI - Ultrasonic wound debridement. AB - Current management of hand injuries includes debridement by abrasive scrubbing with anti-bacterial detergents, surgical excision, or pressure irrigation. A rat model with a contaminated laceration was used to study the efficacy of ultrasonic debridement to diminish bacterial counts and particulate matter in open wounds. Ultrasonic debridement of hand wounds has several advantages over the current methods of wound debridement. These include a technically simple procedure that is effective in the removal of particulate matter and the reduction of bacterial counts (p less than 0.005). In addition there was no blood loss and no detectable damage of viable tissues as evaluated by electron microscopy. This technique may prove to be a significant advance in the early management of hand wounds. PMID- 3351221 TI - Percutaneous phenol blocks of the pectoralis major muscle to treat spastic deformities. PMID- 3351222 TI - Measurement of grip strength in the diagnosis of wrist pain. AB - Grip strength was assessed in patients with chronic wrist pain and correlated with the results of subsequent bone scans and pathology. The results showed a highly significant decrease of grip strength in patients with positive bone scans or confirmed wrist pathology compared with those with negative bone scans (p less than 0.01). We conclude that the detection of weakness of grip is a simple indicator of true pathology in "obscure" wrist pain. PMID- 3351223 TI - Acquired Madelung-like deformity in a gymnast. AB - High-level gymnastic training may cause clinical and radiographic changes in the wrist. A case is reported demonstrating bilateral closure of the ulnar side of the distal radius epiphyseal plate in a patient with a history of high-level gymnastic training. Cumulative microtrauma to the ulnar side of the distal radius epiphyseal plate may cause premature closure leading to a Madelung-like deformity. PMID- 3351224 TI - Emergency free flaps to the upper extremity. AB - Thirty-one emergency free flaps were applied to the upper extremities of patients who ranged in age from 16 to 57 years. The size of the skin defects ranged from 13 to 540 square centimeters, with an average of 145 square centimeters. A variety of flaps were used, including 14 lateral arm, seven groin, five latissimus, three first web space of the foot, one scapular and one medial arm. In patients with small defects, the operative time ranged from 3 to 9 hours, with an average of 4 hours and 54 minutes. The hospital stay was never longer than 4 days. In patients with medium size defects, the operating time ranged from 3 to 18 hours, with an average of 7 hours and 45 minutes. The hospital stay averaged 7.4 days. In large defects in which extensive reconstruction was undertaken before flap application, the operative time ranged from 3 to 20 hours, with an average of 11 hours and 54 minutes. The average hospital stay was 11.8 days. Twenty-nine of the 31 flaps survived in their entirety (93.5%). In one of the successful flaps (3.2%), exploration was required after the patient left the operating room. Severe infection occurred in only one case, that being one of the two flap failures. Twenty-seven of the 31 patients returned to work, 18 of them to their original employment. PMID- 3351225 TI - Free vascularized nail grafts. AB - A considerable amount of literature has been written on microneurovascular surgery for the reconstruction of partial defects in fingers, but little has been published on reconstruction to replace lost fingernails. We report on two clinical cases in which a free vascularized nail graft and a "double onychocutaneous flap" were used successfully. We suggest that the free vascularized nail graft is a superior method in reconstruction to treat fingernail loss or deformity. PMID- 3351226 TI - Coverage of a carpal tunnel wound dehiscence with the abductor digiti minimi muscle flap. AB - A 41-year-old man who was taking 60 mg of prednisone a day for dermatomyositis developed a wound dehiscence following a carpal tunnel release and flexor tenosynovectomy. Coverage of the exposed carpal contents was provided by using the abductor digiti minimi as a local transposition flap. PMID- 3351227 TI - High-voltage electrical injury: acute pathophysiology. AB - A reproducible high-voltage electrical injury model was established in the primate using a new approach to energy administration, measurement instrumentation, and data acquisition. Patterns of current repartition and temperature generation were examined in 24 primates. The predominant current load was carried in muscle, which is the tissue group occupying the largest cross sectional area. Highest temperature values observed were in muscles of small cross-sectional diameter and in tissues of high inherent resistance. Surgeons should be aware of the principles and the pattern of current distribution when performing early debridement and/or definitive coverage procedures. PMID- 3351228 TI - Accidental hand burns caused by operating room lights. AB - Three patients sustained burns of the hand in the operating room because of the lack of heat shields in the lights. A 54 degrees F increase in temperature in the operating field was noted when the heat shields were not in place. PMID- 3351229 TI - Hydrofluoric acid burns of the hand: mechanism of injury and treatment. AB - Hydrofluoric acid is one of the strongest inorganic acids and is used extensively in industry and research. It differs from other acids in that the fluoride ion readily penetrates the skin, causing destruction of deep tissue layers and even bone. Authors have previously described numerous topical treatments. This report describes one method of treatment emphasizing immediate skin cleansing and the application of calcium gluconate gel, which is followed by calcium gluconate subcutaneous injections when necessary. An accurate occupational history and physical examination are important aspects of patient assessment. Prompt treatment resulted in relief of pain and a satisfactory clinical result in all cases. A significant delay in treatment was responsible for permanent impairment in 2 of 14 patients. PMID- 3351230 TI - Histogenesis of Dupuytren's disease: an immunohistochemical study of 30 cases. AB - Thirty-seven specimens from the hands of 30 patients with Dupuytren's disease were examined by light microscopy after immunohistochemical staining for the presence of desmin intermediate filaments. Results indicated that desmin-positive cells were present in the proliferative Dupuytren's nodules, and that the number of desmin-positive cells decreased significantly in the fibrous phase of the disease. Also, on the basis of the pattern of distribution of the desmin-positive cells around vessels, we postulate that the desmin-positive cells in Dupuytren's nodules were migrating perivascular smooth muscle cells from the vessel wall. The exact fate of these cells is uncertain, but we hypothesize that these displaced perivascular smooth muscle cells are capable of transforming into collagen producing, desmin-negative myofibroblasts that form the cellular basis of Dupuytren's lesions. PMID- 3351231 TI - Lipofibromatous hamartoma of nerve. AB - Seventeen cases of lipofibromatous hamartoma of nerve (14 with histologic confirmation) were treated between 1935 and 1985. One patient had bilateral involvement. Fourteen lesions were located in the upper extremity and four in the lower extremity. Twelve of the 18 lesions were associated with combined soft tissue and skeletal enlargement, or true macrodactyly. Three other lesions had soft tissue enlargement other than that noted intraneurally. Three patients were treated with carpal tunnel release alone and 14 with combined procedures to decrease the size of the affected part. Sensibility in the affected part often appeared unrelated to removal or preservation of hamartomatous nerve tissue. Complications related to nerve surgery included recurrence of carpal tunnel syndrome in one patient, recurrent soft tissue mass in one patient, and painful calcification of the involved tissues 20 years postoperatively in one patient. PMID- 3351232 TI - Hemangiopericytoma of the median nerve. AB - This is a case report of a hemangiopericytoma located within the median nerve at the wrist in a 79-year-old man. The tumor was removed without loss of function. PMID- 3351233 TI - Reconstruction and pathology in macrodactyly. AB - We report a case of macrodactyly in which a finger was shortened and the nail bed and root implanted proximally using a vascularized pedicle. Electron microscopic findings showed that there was focal and segmental degeneration of myelin sheath and neurofilaments of axon. PMID- 3351234 TI - Congenital synostosis between the fourth and fifth metacarpal bones. AB - Congenital synostosis between the fourth and fifth metacarpals is a rare congenital anomaly. This article reports the clinical features, hand pattern profiles, and dermatoglyphics of 14 patients with congenital synostosis between their fourth and fifth metacarpals. Surgical procedures are discussed. PMID- 3351235 TI - Congenital pseudarthrosis of the forearm. AB - Congenital pseudarthrosis of the forearm is a rare condition in which traditional treatment methods have proven unsatisfactory. We report a case of congenital pseudarthrosis of the radius and ulna successfully treated by resection of the distal ulna and excision of the radial pseudarthrosis with replacement by an interpositional free vascularized fibular graft. PMID- 3351236 TI - Congenital absence of the fourth metacarpal bone (congenital dysplasia of the ring finger). AB - Review of the related literature shows no reports of congenital absence of the fourth metacarpal or congenital dysplasia of the ring finger. I describe the clinical features, hand pattern profiles, and dermatogyphics of three patients with displastic floating ring finger. The surgical treatment is outlined. PMID- 3351237 TI - Small finger pollicization in the radial club hand. AB - This article describes pollicization of the small finger. A procedure that should only be used in the rare instance of an inoperable radial club hand. Children with bilateral radial club hands and severe, fixed radial deviation of the hand at the end of the forearm, and stiff elbows that cannot be mobilized either with a tendon transfer, splinting, or triceps release can be considered candidates for this operation. The technique, as described by Dieter Buck-Gramcko for pollicization of the index finger, was modified to be used in this procedure. PMID- 3351238 TI - The brachioradialis: anatomy, properties, and value for tendon transfer in the tetraplegic. AB - We have studied the brachioradialis muscle both physiologically and clinically for its suitability for tendon transfer in the tetraplegic. Intraoperative measurements have shown that the muscle is strong, provides excellent excursion, and is commonly available for transfer in the absence of other candidate muscles. The anatomic features that limit its use can be overcome during the operation. Postsurgical assessment of the muscle using electromyography and muscle-force measurement have shown that the muscle is voluntarily activated and provides strength for the intended function. Our experience with transfer of the brachioradialis to the hand of a tetraplegic patient has been highly positive. PMID- 3351239 TI - Evaluation of the humpback scaphoid by computed tomography in the longitudinal axial plane of the scaphoid. AB - The deformity known as the humpback scaphoid is difficult to visualize on radiographs. Three patients were studied by imaging with computerized axial tomography (CT scan) in the true longitudinal axis of the scaphoid. This projection demonstrates the anatomy, allowing assessment of fractures, the humpback deformity, and the shape of the scaphoid after grafting. PMID- 3351240 TI - Diagnosis of dorsal and palmar rotation of the lunate on a frontal radiograph. AB - Anatomic variations in the contours of the palmar and dorsal horns of 100 dry lunates were classified by symmetry, curvature, and angularity. Frequencies of the major forms were determined. An algorithm was constructed for the identification of the dorsal and palmar horns of the lunate on a frontal radiograph. By this algorithm, it is possible to diagnose intercalated segment instabilities without the use of a lateral radiograph. PMID- 3351241 TI - Failed distal ulna resections. AB - Twenty patients with complaints of pain and limitation of activities for more than 1 year after ulnar head resection (Darrach) were studied. Their ages ranged from 18 to 60 years (mean, 38 years). The initial indications for operation were posttraumatic derangement in 18 patients, radial growth anomaly in 1, and a lesion of the ulna in 1. Follow-up ranged from 29 to 135 months (mean, 61 months). The patients had an average of 2.2 additional operations, with up to seven procedures per patient. Radiographs were compared with those from an equal number of successful Darrach resections chosen randomly, and no significant differences were noted. All 20 patients continue to have difficulties despite several years of treatment. The Darrach resection can result in serious disability, especially in the younger patient and the patient with lax ligaments. Reoperation on these patients is rarely successful. PMID- 3351243 TI - Treatment of chronic perilunate dislocations. AB - Fifteen patients with 16 perilunate dislocations that had been untreated for a minimum of 6 weeks after the injury were evaluated after subsequent treatment at a mean of 6.4 years. The median time from injury to definitive treatment was 17 weeks. Ten wrists had completely ligamentous injuries and six had fracture dislocations. Treatment consisted of open reduction and internal fixation in six patients, isolated carpal bone excision in four, wrist arthrodesis in two, proximal row carpectomy in two, and bilateral carpal tunnel release in one. In this series the results of excision of the lunate or scaphoid alone were uniformly poor. One of the two patients who had a proximal row carpectomy required secondary radial styloidectomy, and a pseudarthrosis developed in one of the two patients who had a wrist arthrodesis. All six patients treated by open reduction and internal fixation had satisfactory outcomes and none required additional surgery. PMID- 3351242 TI - Silicone wrist implant: long-term follow-up study. AB - Nineteen patients with 20 silicone rubber wrist implants of the Swanson design were followed for an average of 6 years. Sixty-five percent of the patients experienced little or no wrist pain after the operation. There was an average of 24 degrees of wrist flexion and 21 degrees of extension. Implant fracture occurred in 65% of the patients. This was not necessarily correlated with clinical symptoms. Subsidence of the implant occurred 100% of the time. Revision procedures were done after six (30%) of the procedures. There was no evidence of radiographic change suggesting silicone synovitis. There is a progressive deterioration in the radiographic appearance and the clinical result after use of this implant. Salvage by means of radiocarpal arthrodesis, or a soft tissue arthroplasty, has been successful in our patients. PMID- 3351244 TI - Irreducible trans-scaphoid perilunate dislocation. AB - Two cases of irreducible trans-scaphoid perilunate dislocation are described. In each case there was soft tissue interposition between the proximal and distal elements of the fracture-dislocation and this prevented capitolunate and scaphoid reduction. The dorsal capsule was impaled on the distal scaphoid fragment in one case, and a flap of dorsal capsule was entrapped between the capitate and the lunate in the other. In light of these findings, we recommend a dorsal approach for open reduction of trans-scaphoid perilunate dislocation when the capitolunate joint cannot be reduced by closed manipulation. PMID- 3351246 TI - Rupture of the flexor pollicis longus tendon associated with an ununited fracture of the scaphoid. AB - A 66-year-old man was admitted to the Department of Orthopaedic Surgery, Aarhus County Hospital a few hours after spontaneous rupture of the left flexor pollicis longus tendon. At operation the tendon was found to be ruptured at the radiocarpal level, where an opening to the radiocarpal joint was found. Radiographs showed a long-standing ununited fracture of the scaphoid. PMID- 3351245 TI - Internal vascularity of the scaphoid in cadavers after insertion of the Herbert screw. AB - This article describes the effects of various operative exposures for insertion of the Herbert screw on the internal vascularity of the scaphoid. Vessels supplying the proximal 70% to 80% of the scaphoid were intact in all specimens except one, which had a combined palmar and dorsal. approach. Vessels supplying the tubercle and the distal 20%-30% were disrupted in five of 18 specimens undergoing the palmar approach. The palmar approach did not disrupt the significant dorsal blood supply, and the dorsal approach was safe provided care was taken to preserve the visible dorsal vascular leash. PMID- 3351247 TI - Avulsion of the flexor digitorum profundus: anatomic and biomechanical considerations. AB - Avulsion of the profundus insertion occurs most commonly in the ring finger. The exact reason for this predilection is unknown. Clinical observation of patients with this injury reveals that a common finding is that the ring fingertip is usually more prominent or "longer" than any other fingertip during grip. A laboratory investigation shows that during grip the ring fingertip becomes 5 mm more prominent than any other digit in 90% of subjects and that it absorbs more force than any other finger during pull-away testing. These factors contribute to the susceptibility of the ring finger to the profundus avulsion injury. PMID- 3351248 TI - Delayed repair of flexor profundus tendon in the palm (zone 3) with superficialis transfer. AB - Transfer of a flexor superficialis tendon was done in an attempt to restore flexor profundus function, as a secondary procedure, in the palm (zone 3) in 16 hands. These were cases in which direct repair was not possible. Eight patients achieved a total active motion (TAM) above 200 degrees and two more were above 180. Of those eight with TAM above 200 degrees four required a secondary tenolysis to improve to that level. Transfers in six patients were regarded as failures. Failures were associated with a poor tendon bed and noncompliant patients. This is a procedure that has limited indication in a cooperative patient with a good tendon bed who reports late with both flexor tendons cut in zone 3. PMID- 3351249 TI - Transfer of the flexor carpi ulnaris to the radial wrist extensors in cerebral palsy. AB - Fourteen patients with cerebral palsy who had had transfer of the flexor carpi ulnaris (FCU) to the extensor carpi radialis longus (ECRL) and/or extensor carpi radialis brevis (ECRB) were examined. Two questions were posed: (1) What was the postoperative arc of active wrist motion? and (2) Did the procedure improve the grasp and release mechanism in hand function? The procedure was successful in the majority of patients; wrist arc of motion was improved and grasp and release was enhanced after operation. PMID- 3351250 TI - Growth of autografted tendons: an experimental study in vivo. AB - The growth of transplanted tendons was investigated in 54 young chickens. The transplantations were done within the first week of life. The flexor digitorum profundus tendon in the digital sheath of the right third digit was replaced by a graft taken from the same tendon of the left third digit. The growth of the grafted tendons was measured and compared with control tendons at the first, fifth, tenth, fifteenth, and twentieth week after the operation. Five weeks after operation the grafted tendons showed the same growth rate as the control tendons. Although tendon growth was retarded compared with the control tendons 15 weeks after operation, it was not statistically different at 20 weeks. PMID- 3351251 TI - Tendon xanthoma: a physical manifestation of hyperlipidemia. AB - Tendon xanthoma, a nonneoplastic tumor of tendon is a significant physical manifestation of hyperlipidemia. These lesions may accompany rapidly progressive atherosclerosis and may signal the presence of life threatening hyperlipidemia. We have seen three patients with tendon xanthoma, and one patient was treated by surgical excision of large xanthomas arising from the substance of the extensor tendons over the metacarpophalangeal (MP) joints of the hand. Because these lesions arise from the substance of the extensor tendons complete removal may result in loss of tendon continuity and function. Surgery in the form of subtotal excision is advised for functional or cosmetic reasons. Although incomplete removal may be associated with recurrence, appropriate medical management may prevent or delay this recurrence. PMID- 3351252 TI - The extensor carpi radialis intermedius tendon. AB - I examined 312 arms from 156 cadavers in the anatomy laboratory of Loma Linda University to find the incidence of the extensor carpi radialis intermedius tendon. I found 29 bodies (12%) that had a good extensor carpi radialis intermedius. In 17 of these 29 bodies, an extra tendon was found bilaterally. Thirty-two extensor carpi radialis intermedius tendons were suitable for transfer operations, and seven were unacceptable. One must be careful to differentiate between a true extensor carpi radialis intermedius tendon and accessory tendinous bands. The relatively high incidence rate and percentage of tendons suitable for transfer operations make this tendon potentially valuable in treating severe quadriplegia with tendon transfers. It can be used successfully for thumb opposition, to motor the flexor pollicis longus, or as a motor for the extensor pollicis longus of the thumb. PMID- 3351253 TI - Comparative mechanical properties of various Kirschner wire configurations in transverse and oblique phalangeal fractures. AB - A biomechanical study assessed the comparative mechanical properties of various wire configurations used in transverse and oblique phalangeal fractures. The configurations included crossed, oblique, and intramedullary wire techniques using 0.028-inch diameter (d) or 0.035-inch d Kirschner (K) wires. Six different configurations were tested in both the oblique fracture pattern and in the transverse fracture pattern. The mechanical properties were determined after either oblique or transverse osteotomy and fixation of the proximal phalanx. Each fixation technique was tested in apex palmar, apex dorsal, and lateral bending, as well as in torsion and distraction. The results showed that of the configurations tested, four crossed 0.028-inch d Kirschner wires obtained the highest rigidity in the transverse fracture pattern and three oblique 0.035-inch d Kirschner wires obtained the highest rigidity in the oblique fracture pattern. PMID- 3351254 TI - A protocol for the treatment of severe infections of the hand. AB - A protocol for the treatment of hand infections was used for 69 patients in a university teaching hospital. The protocol prescribes incision and drainage under optimal conditions (in the operating room) when the patient is first seen and intravenous antibacterial therapy effective against anaerobic and aerobic bacteria initiated immediately after obtaining aerobic and anaerobic cultures. Results of bacteria studies confirmed the significant frequency (nearly 30%) of mixed aerobic and anaerobic infection. Use of the protocol resulted in a shorter hospital stay, faster healing, and fewer complications (recrudescence of infection, reoperation, stiffness, arthritis, and osteomyelitis) when compared with 107 patients who were treated before institution of the protocol. PMID- 3351256 TI - Compression of the deep branch of the ulnar nerve at the adductor hiatus producing pain without muscle atrophy. AB - Compression of the deep branch of the ulnar nerve distal to the pisohamate hiatus is rare. Two cases of compression of the deep branch at the adductor hiatus are presented. These cases are unique because of pain in the hand without muscle atrophy. One patient has had surgical treatment, and the other patient's symptoms are not severe enough to warrant surgical treatment. PMID- 3351255 TI - The effect of intraoperative ischemia on the recovery of contractile function after free muscle transfer. AB - Isometric contractile function was studied after recovery in free, vascularized muscle transfer subjected to graded periods of intraoperative ischemia. Fifteen dogs had orthotopic replantation of their left gracilis muscles, with intraoperative ischemia times grouped as 0 (n = 3), 1 to 2 (n = 3), 2 to 3 (n = 4), or 3 to 4 (n = 5) hours. After recovery (mean 61.8 weeks), isometric twitch and tetanic tension and fatigue measurements were made in the replants and in the contralateral, control gracilis. On the average, replants were found to produce significantly less twitch (0.32 +/- 0.13 versus 0.49 +/- 0.24 N/g) and 75 Hz tetanic tension (2.2 +/- 0.9 versus 3.4 +/- 0.5 N/g) than controls. However, in several individual replants, 100% of control maximal tetanic tension was observed. Intraoperative ischemia time of up to 4 hours was not correlated with functional return. It is concluded that (1) full recovery is possible after free muscle transfer; (2) intraoperative ischemia, if less than 4 hours long, is not the primary determinant of functional recovery; and (3) factors besides intraoperative ischemia must be operative in producing the variability in recovery seen in this setting. PMID- 3351258 TI - Therapeutic and functional results of limb salvage to treat sarcomas of the forearm and hand. AB - Twenty-six patients with soft tissue sarcomas of the forearm and hand were treated with limb salvage protocols involving surgical wide excision, chemotherapy, and radiation therapy. Six received immediate or delayed reconstructive surgery to improve function. The average delay from the time of the first medical consultation until the correct diagnosis was made was 4.5 months. The average follow-up period was 44 months; a 91% survival rate was observed, with an 8% rate of local recurrence. Functional abilities were assessed by a questionnaire concerning work, household activities, and overall satisfaction with the surgical result. Eight-six percent of the patients had an excellent functional result, and 84% reported excellent satisfaction with their operation. PMID- 3351257 TI - Immediate amputation stump coverage with forearm free flaps from the same limb. AB - When the traumatic amputation level or the degree of damage to the arm or forearm does not justify reimplantation of the severed part there may be sufficient undamaged skin to be used as a free flap to resurface the arm or the stump. Stump length or the elbow joint may thus be preserved and more durable skin cover for the fitting of a prosthesis may be obtained. A "spare-parts" forearm free flap may be raised on the radial or ulnar vessels or both. Three cases are reported. PMID- 3351259 TI - Excision of the lunate in paraplegic patient. PMID- 3351260 TI - Kleinert splint. PMID- 3351261 TI - Erosion of triquetrum. PMID- 3351262 TI - Extensor tendon involvement in Smith's and Faleazzi's fractures. PMID- 3351263 TI - Reusable latex gloves. PMID- 3351264 TI - AIDS in a blood bank technician in Mexico City. PMID- 3351265 TI - Infection control practices for preventing respiratory syncytial virus infections. PMID- 3351266 TI - Prevention of nosocomial transmission of respiratory syncytial virus in a newborn nursery. AB - During three winter seasons prior to 1984-1985 the special care nursery at New England Medical Center experienced respiratory syncytial virus (RSV) epidemics that required closure of the unit. Prior to and during the 1984-1985 winter season, several measures were taken to prevent recurrent nosocomial RSV transmission. In the winters of 1984-1985 and 1985-1986 there were 26 introductions of community-acquired RSV with no transmission of nosocomial cases during 1,688 patient days at risk as compared with 1983-1984 when there were seven cases of nosocomial RSV following six introductions of RSV during 875 patient days at risk (rate = 8 per 1,000 patient days) (P = 0.0016). The institution of many infection control measures including active surveillance, cohorting infected patients, a strict winter visiting policy, and gowning, gloving, and applying mask on contact, was associated with the successful prevention of nosocomial transmission of RSV in this nursery setting. PMID- 3351268 TI - Effect of bedside needle disposal units on needle recapping frequency and needlestick injury. AB - Needle recapping has been shown to be one of the leading causes of needlestick injuries. Frequency of recapping has not been reported. This study was designed to determine the frequency of needle recapping by nursing personnel and the effect of bedside needle disposal units on the frequency of recapping and needlesticks. Seventy-four nurses carrying out 312 activities involving use of needles were observed. The subjects were not aware of the nature of the study. The recapping frequency was 93.9%. The study was repeated after educational programs and following installation of a hospital-wide bedside needle disposal system. Fifty-three nurses performing 151 activities with needles were observed. Frequency of recapping was 94%. There was no significant difference in the rate of recapping or needlestick injuries after installation of the new needle disposal system. Educational programs regarding recapping, a very common practice, may be ineffective. Alternate methods for preventing needlesticks may be necessary. PMID- 3351269 TI - The detection of blood on gloved hands of central sterile supply personnel and cleaned instruments used for procedures on patient units. PMID- 3351270 TI - Tuberculin testing, BCG in pregnancy. PMID- 3351267 TI - The impact of preoperative skin disinfection on preventing intraoperative wound contamination. AB - The efficacy of total body showering and incision site scrub with disinfectant agents was evaluated in a randomized, prospective study of 575 patients undergoing selected surgical procedures. Patients who showered twice with 4% chlorhexidine gluconate had lower mean colony counts of skin bacteria at the surgical incision site in the operating room prior to the final scrub than patients who showered twice with povidone-iodine solution or medicated bar soap. Patients in the chlorhexidine group had no growth on 43% of the incision site skin cultures compared with 16% in the povidone-iodine group and 6% in the soap and water group. Patients who showered and who were scrubbed with chlorhexidine also had lower rates of intraoperative wound contamination. Bacteria were recovered from the wounds of 4% of patients using this regimen compared with 9% for patients who used povidone-iodine and 15% for patients who showered with medicated soap and water and were scrubbed with povidone-iodine. We noted no difference in surgery-specific infection rates among patients in the three treatment groups; however, our sample sizes were too small to evaluate this outcome parameter adequately. These data suggest that preoperative showering and scrubbing with chlorhexidine is an effective regimen to reduce extrinsic intraoperative contamination of the surgical wound from skin bacteria. The efficacy of this regimen to prevent postoperative wound infection needs to be evaluated in a well-designed, carefully controlled prospective trial with adequate numbers of patients to achieve statistically valid conclusions. PMID- 3351271 TI - Legal comment, Part I: Basics of liability law. PMID- 3351272 TI - Catheter irrigation and long-term patients. PMID- 3351273 TI - Emergency endotracheal intubation. PMID- 3351274 TI - Reflections on values. PMID- 3351275 TI - Management of pain in patients with myocardial infarction. PMID- 3351276 TI - The importance of data in verifying nurse staffing requirements. PMID- 3351277 TI - The psychological response of patients to admission to coronary care for heart disease, and its' effects on rehabilitation. PMID- 3351278 TI - Cultural values--influence on the delivery of care. PMID- 3351279 TI - Coronary heart disease--a subjective perspective. PMID- 3351280 TI - Basic life support--the forgotten skills? PMID- 3351281 TI - Cost awareness by family practice residents of commonly used laboratory tests, X ray tests and medications. PMID- 3351282 TI - ISMA addresses problems associated with prescription drug misuse. PMID- 3351284 TI - California court action. Physicians bear responsibility in utilization review. PMID- 3351283 TI - Questioning the physician's broader responsibilities. PMID- 3351285 TI - Teachers as role models. PMID- 3351286 TI - Supraventricular aberrancy. PMID- 3351287 TI - Bronchiolitis. Experience at Methodist Hospital of Indiana, 1981-1986. PMID- 3351288 TI - Birth defects registries: a survey of state programs. PMID- 3351289 TI - Electrophysiologic directed endocardial resection and cryoablation in the treatment of ventricular tachyarrhythmias. PMID- 3351290 TI - Role modeling. PMID- 3351291 TI - The vacuum cleaner. PMID- 3351292 TI - How physicians can manage risk and decrease liability insurance costs. PMID- 3351293 TI - Vascular structure enhances regional resistance responses in mild essential hypertension. AB - Forearm blood flow (FABF) and forearm vascular resistance (FAVR) responses to sequential regional infusions of norepinephrine (NE) and angiotensin II (Ang II) were examined in 24 hypertensive and 18 matched normotensive subjects. Sensitivity to both vasoconstrictors, defined as the percentage increase in FAVR in response to the lowest dose of each agonist, was similar in the two groups. Also, the FABF response curve to the full range of both agonists did not differ between hypertensives and normotensives by analysis of variance (ANOVA). While the FAVR responses at the lowest doses of both NE and Ang II were similar in hypertensives and normotensives, FAVR responses in hypertensives diverged progressively from the normotensive response pattern, P less than 0.01 according to ANOVA. The hypertensives achieved greater maximum FAVR levels at the highest doses of both agonists, P less than 0.05 according to repeated measures ANOVA. After 10 min of ischaemic exercise, FAVR was higher in hypertensives than in normotensives (2.24 +/- 0.10 versus 1.87 +/- 0.08; P = 0.02, respectively). This value for FAVR was termed the minimum FAVR (mFAVR). The overall response pattern characterized by increased mFAVR, unchanged threshold sensitivity, steeper slope, greater maximum response and similarity of responses to both NE and Ang II is most consistent with a structural augmentation of resistance responses. A model was used in an effort to increase understanding of the vessel morphology. This model suggested that an increased wall/lumen ratio, perhaps without an actual increase in vascular smooth muscle mass, played an important role in the observed FAVR pattern. PMID- 3351294 TI - Blunted aldosterone responsiveness to angiotensin II in normotensive subjects with familial predisposition to essential hypertension. AB - The responsiveness of plasma aldosterone to an angiotensin (Ang) II infusion was assessed in normotensive young men, nine without and 13 with a family history of essential hypertension, after 7 days of low (mean urinary sodium 12 +/- 10 mmol/24 h) and 7 days of high (269 +/- 92 mmol/day) sodium intake. Under both conditions, the two study groups did not differ in body weight, arterial pressure, heart rate, plasma or urinary sodium and potassium or plasma renin, aldosterone or Ang II levels. However, after both dietary periods, the relationship between plasma aldosterone and plasma Ang II concentrations had shifted significantly (P less than 0.01) to the right in predisposed compared to non-predisposed subjects. The sodium-related changes in adrenocortical sensitivity to Ang II were similar in the two groups. The pressor response to Ang II did not differ between the two groups of subjects. These findings suggest that, in addition to the known cardiovascular abnormalities of sympathetic, renal and ion transport mechanisms, a fourth area of disturbance involving the response of plasma aldosterone to Ang II may be present in normotensive subjects with familial predisposition to essential hypertension. PMID- 3351295 TI - The relation of cellular sodium to the onset of hypertension induced by DOCA saline in the rat. AB - Groups of 15 rats were injected subcutaneously with a microcrystalline suspension of DOCA and given 1% saline as drinking water for periods ranging from 2 to 16 days. The in vivo transmembrane distribution of Na and K in relation to blood pressure was assessed in terms of plasma [Na] and [K] measured with ion-specific electrodes; smooth muscle cell Na, K and water were measured in the rapidly excised tail artery. A small increase in blood pressure was observed in week 1 of treatment and was followed by an abrupt increase to higher levels at about day 10. Plasma [Na] was elevated and [K] lowered throughout in a new steady state with a reciprocal change of about 1 mmol/l. There were minor changes in intracellular [K] in rapidly excised fresh tail artery samples so that the transmembrane K gradient (EK) was at all times increased by greater than 10 mV, indicating enhanced Na-K transport. In general, intracellular [Na] was directly and Na gradient inversely related to blood pressure (P less than 0.01). PMID- 3351296 TI - Cytosolic free calcium in platelets: relationships to blood pressure and indices of systemic calcium metabolism. AB - Relationships between cytosolic free calcium ([Ca2+]i) in platelets, indices of systemic calcium metabolism and blood pressure were examined in 86 subjects; 29 patients with untreated and 29 patients with treated essential hypertension, six patients with borderline hypertension and 22 healthy reference subjects. In order to analyse interactions between the variables, multivariate statistical analyses were employed. The patients with untreated hypertension had higher [Ca2+]i values in non-activated platelets (P = 0.04) and lower levels of plasma ionized calcium (P = 0.02) than the reference subjects. In multivariate models analysing platelet [Ca2+]i mean blood pressure (MBP), plasma ionized calcium, serum parathyroid hormone (PTH) and body mass index (BMI), the relationship between platelet [Ca2+]i and blood pressure was attenuated (P = 0.13), whereas the inverse relationships between plasma ionized calcium and MBP (P = 0.01) and between platelet [Ca2+]i and serum PTH (P = 0.06) seen in univariate analyses persisted. According to the multivariate models the [Ca2+]i value explained only 5% of the MBP variability. Thus, the data from this investigation do not support a close relationship between basal platelet [Ca2+]i and blood pressure. The inverse relationship between plasma ionized calcium and blood pressure, independent of platelet [Ca2+]i and serum PTH, suggests a direct interaction between plasma ionized calcium and blood pressure regulation. PMID- 3351297 TI - Increased concentration of angiotensin II binding sites in selected brain areas of spontaneously hypertensive rats. AB - We studied the density of the angiotensin II (Ang II) binding site in discrete brain nuclei of 4-week-old and 14-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats by autoradiographic binding techniques. Tissue sections were incubated in vitro with 3 nmol/l [125I]Sar1Ang and results were analysed by computerized microdensitometry and by comparison with 125I-standards. Both young and adult SHR (aged 4 and 14 weeks, respectively) had significantly higher Ang II binding site concentrations in the median preoptic nucleus (MPO), subfornical organ (SFO), paraventricular nucleus (PVN) and nucleus of the solitary tract (NTS) when compared to age-matched WKY control rats. No significant difference was found between strains in other brain areas such as the olfactory bulb, suprachiasmatic nucleus (SCh), inferior olive (IO) and area postrema (AP). It was observed that the concentration of Ang II binding sites increased with age in PVN of both SHR and WKY, while the number of binding sites in the MPO and IO decreased with age. In SHR, alteration in Ang II binding is restricted to brain nuclei involved in the central pressor action of Ang II and seems to be related to the development and maintenance of spontaneous hypertension. PMID- 3351298 TI - Hypertensive episodes and circadian fluctuations of blood pressure in patients with phaeochromocytoma: studies by long-term blood pressure monitoring based on a volume-oscillometric method. AB - A new portable device for the indirect measurement of arterial blood pressure was successfully applied to detect paroxysmal hypertension and circadian fluctuation of blood pressure in patients with phaeochromocytoma. The device utilizes the volume-oscillometric technique, it is equipped with a microprocessor and allows long-term automatic monitoring of indirect blood pressure in the human finger. Compared with conventional fully automated portable devices of the arm-cuff type, our current equipment is lighter, less noisy, and causes less discomfort. With this device repeated measurements can be made without causing stress or discomfort, and without disturbing sleep. The arterial pressure measurement obtained using this device was reliable and reproducible. In some patients certain symptoms, possibly due to phaeochromocytoma, had been observed for several years before the study, although hypertension had not been identified. While these patients had consistently high circulating catecholamine levels, nocturnal falls in blood pressure were clearly documented. This suggests that plasma catecholamines released from the phaeochromocytoma, though excessive, may be of less physiological importance than other regulatory mechanisms concerned with circadian fluctuation of blood pressure, e.g. the sympathetic nervous system and/or hypothalamo-pituitary-adrenal system. This new device has proved to be a reliable means of monitoring long-term blood pressure and is useful in the diagnosis of paroxysmal hypertension in patients with phaeochromocytoma. PMID- 3351299 TI - Models of adrenal regeneration hypertension in the rat. AB - Blood pressure was measured indirectly (using the tail-cuff method) and intra arterially in conscious rats following one of three experimental procedures carried out in order to determine which resulted in the most marked and reproducible form of adrenal regeneration hypertension (ARH). All rats were unilaterally adrenalectomized and given NaCl solution (1%). In some rats, the remaining adrenal gland was either enucleated (AE rats) or compressed (AC rats) but both kidneys were left intact. During the fourth week after surgery, indirectly measured systolic blood pressure was higher in AE and AC rats than in sham-operated (SO) rats but, when measured intra-arterially, the magnitude of the developed hypertension was small (AC rats) or was absent altogether (AE rats). However, when a kidney was removed at the time of enucleation (AEN rats), the levels of systolic blood pressure, measured indirectly or intra-arterially, were markedly and consistently higher than in the corresponding group of uninephrectomized SO rats. The magnitude of the developed hypertension was similar in mature male and immature female AEN rats. We conclude that mature male rats, unilaterally nephro-adrenalectomized and given NaCl solution (1%), provide a marked and reproducible model of ARH. PMID- 3351300 TI - Nisoldipine. Central haemodynamics at rest and during exercise in essential hypertension: acute and chronic studies. AB - Calcium blockers may reduce contractility of vascular smooth muscle as well as that of myocardial cells. Therefore, falls in both total peripheral vascular resistance (TPR) and cardiac output (CO) might be responsible for a fall in blood pressure (BP) caused by calcium blockers in essential hypertension. We have studied the acute and chronic haemodynamic effects of nisoldipine (a new calcium blocker) in 19 patients with essential hypertension at rest in the supine and sitting positions and during 100-W dynamic exercise to investigate whether CO might be compromised by acute and chronic calcium blockade. Intra-arterial pressure, CO (by Cardiogreen), stroke volume, heart rate and TPR were measured hourly after the first dose of 10 mg nisoldipine (acute study) and then after 1 year of nisoldipine treatment (mean dose 25 mg; chronic study). The maximal first dose response was seen after 1 h, i.e. a fall in intra-arterial pressure (9%) and TPR (19%) and a reflex rise in heart rate (9%) and CO (12%). The effects levelled off during the next 2 h. After 1 year of treatment there was a more marked reduction in BP: at rest intra-arterial pressure fell (14% supine, 16% sitting) due to fall in TPR (19%) but without significant changes in heart rate or CO; during 100-W exercise, intra-arterial pressure fell (14%) due to reduction in both TPR (7%) and CO (6%). In conclusion, nisoldipine lowers BP by reducing TPR, both acutely and chronically. The initial reflex tachycardia and rise in CO disappear during long-term treatment, probably due to resetting of the baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351301 TI - The role of the C9b domain in the binding of C9 molecules to EAC1-8 defined by monoclonal antibodies to C9. AB - Three mAb to human C9, X195, X197, and P40 were used to analyze the roles of the C9a and C9b domains in the reaction of the C9 molecule with sensitized sheep E bearing C1 to C8 (EAC1-8). X195 bound to NH2-terminal (C9a) fragments, and X197 bound to COOH-terminal (C9b) fragments obtained by cleavage of C9 with alpha thrombin or trypsin. P40 recognized the epitope on the C9b fragment obtained by alpha-thrombin cleavage but did not react with the NH2-terminal or COOH-terminal fragment obtained by trypsin cleavage. In this respect, P40 differed from mAb to C9 reported previously. P40 almost completely inhibited the hemolytic activity of C9. X195 and X197 also inhibited C9 activity, but less effectively than P40. C9 molecules bound to P40 could not bind to EAC1-8 cells. C9 bound to X197 could not bind rapidly to EAC1-8, but prolonged incubation of the C9-X197 complex with EAC1 8 caused considerable lysis of the cells. C9 molecules bound to X195 could bind rapidly to EAC1-8, but their lytic activity was partially inhibited by the bound antibody. From these results, it is concluded that the C9b but not C9a domain contributes to the binding of C9 to EAC1-8 and that the epitope recognized by P40 or a closely adjacent site may be the binding site of C9 molecule to EAC1-8. PMID- 3351302 TI - Macrophage migration in fibrin gel matrices. II. Effects of clotting factor XIII, fibronectin, and glycosaminoglycan content on cell migration. AB - We investigated the migration of oil-induced, guinea pig peritoneal macrophages in three-dimensional fibrin matrices, with particular attention to variables which modified fibrin gel structure and/or its adhesive properties for cells. The variables studied were fibrin concentration, gel cross-linking, and fibronectin and glycosaminoglycan content. Macrophage migration was an inverse linear function of fibrinogen concentration. Little or no fibrinolysis accompanied macrophage migration; rather, macrophages migrated through fibrin gels by an active process associated with marked distortions of cell shape and specialized plasma membrane contacts with fibrin strands. Fibrin matrices prepared from fibrinogen that had been depleted of clotting factor XIII and/or fibronectin provided a superior matrix for macrophage migration. Both the number of migrating cells and distance of migration were reduced when the gel matrix included fibronectin and was cross-linked by factor XIII. A hexapeptide containing the fibronectin cell-binding RGDS sequence reversed this migration inhibition, suggesting that fibronectin immobilized by cross-linking to fibrin may have bound macrophages and restricted cell migration. Hyaluronic acid, heparin, and heparan sulfate inhibited macrophage migration in cross-linked fibrin-fibronectin gels over a range of concentrations. These data are relevant to an understanding of macrophage migration in vivo where cross-linked fibrin-fibronectin gels containing variable amounts of glycosaminoglycans are deposited in tissues in immunologic reactions and in many other types of pathology. PMID- 3351303 TI - Role of leukotrienes in vascular changes in the rat mesentery and skin in anaphylaxis. AB - The role of leukotrienes and other mediators of vascular changes in anaphylaxis were studied in rats sensitized with monoclonal anti-DNP IgE and challenged with DNP-BSA. Microvascular changes in the mesentery were followed by intravital fluorescent microscopy and in the skin by exudation of Evans blue dye. Administration of Ag i.v. caused a marked increase in the peristaltic movement of the intestine, plasma exudation, and arteriolar constriction in the mesentery. The microvascular changes were accompanied by a profound fall in blood pressure, which was biphasic. The first phase lasted for approximately 2 min. The second phase was very prolonged and the hypotension was still maintained 40 min after Ag challenge. The changes observed were dose dependent with regard to Ag. Intradermal application of Ag resulted in dose-dependent extravasation of Evans blue dye in the skin. Plasma exudation was partially inhibited by pyrilamine and methysergide. However, their effect seemed to be more pronounced in the skin than in the mesentery. The leukotriene D4-R antagonist L-649,923 and the 5 lipoxygenase inhibitor ONO-LP-049, alone or in combination with other inhibitors, did not alter the plasma leakage in the skin. In the mesentery, the leukotriene antagonists alone had a moderate effect on vascular permeability. However, the combination of these agents with pyrilamine completely inhibited macromolecular extravasation. The hypotension was modulated by the antihistamines as well as the leukotriene and serotonin antagonists. Pyrilamine inhibited the first phase and the second phase. The major effect of methysergide was a decrease in the duration of the hypotension. This was especially evident when it was administered in combination with other inhibitors. The leukotriene antagonists when given alone had moderate effects on the blood pressure changes. However, in combination with pyrilamine, the hypotension was substantially reduced. Leukotrienes appeared to be important mediators of the vascular changes in the mesentery but not in the skin (passive cutaneous anaphylaxis). They markedly potentiated the action of histamines. PMID- 3351304 TI - A direct in vivo comparison of the inflammatory properties of human C5a and C5a des Arg in human skin. AB - C5a is an 11,000-Da complement-derived inflammatory glycoprotein that has been shown to mediate inflammatory reactions in vitro as well as in vivo in human skin. The C5a degradation product, C5a des Arg, is rapidly formed after exposure of C5a to serum carboxypeptidase N and may represent the relevant C5-derived inflammatory peptide in vivo. To examine the biologic activity of human C5a des Arg in vivo and to compare it with that seen with human C5a, we purified and characterized homogeneous preparations of human C5a and C5a des Arg and injected them intradermally into seven normal volunteers. C5a des Arg exhibited biochemical and biologic properties in vitro that were different from those of C5a. When injected into human skin, C5a des Arg was less potent than C5a, in respect to both minimal dose eliciting wheal and flare reactions and maximal wheal and flare elicited at a given dose, but C5a des Arg still elicited cutaneous wheal and flare reactions at physiologically relevant concentrations. Histologically, C5a des Arg skin test sites showed dense polymorphonuclear neutrophil-rich infiltrates associated with leukocytoclasis, dermal mast cell degranulation, and endothelial cell swelling. These were virtually indistinguishable from reactions elicited by C5a and occurred with concentrations attainable in vivo. Cutaneous wheal and flare reactions elicited by either C5a or C5a des Arg were partially inhibited by H1 antihistamines but were unaffected by selected nonsteroidal anti-inflammatory agents. PMID- 3351305 TI - Lysis of a lung carcinoma by poly I:C-induced natural killer cells is independent of the expression of class I histocompatibility antigens. AB - Cells from the line 1 murine carcinoma express little if any H-2d when grown in normal medium. These cells are susceptible to splenic cell populations with NK activity, stimulated by prior injection of poly I:C, but are not lysed by NK deficient splenocytes from homozygous beige mice treated with anti-asialo GM1. Incubation of line 1 cells in medium containing DMSO leads to a dramatic stimulation of H-2d expression but no change in lytic susceptibility to splenic NK cells. Transfection of H-2Dp into line 1 leads to a constitutive and DMSO inducible expression of H-2Dp at functionally significant levels, but this expression appears to have no influence on NK cytolytic susceptibility. PMID- 3351306 TI - Corrected nucleotide and amino acid sequences for H-2Dk subclone pH2III. PMID- 3351307 TI - Monoclonal antibodies against the major zymosan-induced chemotactic factor in rabbit serum. AB - The major zymosan-induced chemotactic factor in rabbit serum was purified by a two-step ion exchange chromatography procedure. The purified chemoattractant was used as antigen for production of murine monoclonal antibodies against the major chemotactic factor. The primary screening of the hybridoma cultures was an indirect ELISA using purified chemotactic factor as antigen. The final selection among ELISA-positive clones was performed according to the results obtained in a chemotactic inhibition assay. Six monoclonal antibodies were raised. These antibodies completely abrogated or substantially reduced the chemotactic activity in crude zymosan-activated serum. The chemotactic factor(s) could be absorbed onto an immunosorbent column containing monoclonal antibody and subsequently be specifically eluted with acid. By Western blot analysis the molecular weight of the major chemotactic factor was estimated to be approximately 15,000, and isoelectric focusing indicated a pI of about 9.4. PMID- 3351308 TI - Dot-immunobinding assay as an accurate and versatile technique for the quantification of human IgG subclasses. AB - A dot-immunobinding assay on nitrocellulose membranes has been developed for the quantification of human IgG subclasses using subclass-specific monoclonal antibodies. The advantages of this technique can be summarized as follows: (1) possibility of rapid semi-quantitative evaluation and/or precise quantitation from the same dot-pattern; (2) simple procedure with very good reproducibility; (3) sensitivity for nanogram concentrations of individual subclasses, therefore applicable not only to serum but also to other body fluids with a low content of IgG; (4) very small amounts of test material needed; (5) very good correlation of results with other techniques (ELISA, radial immunodiffusion) but without some of the inherent problems of the latter methods. PMID- 3351309 TI - Chicken antibodies: a tool to avoid false positive results by rheumatoid factor in latex fixation tests. AB - 19 rheumatoid factor (RF)-positive sera (Waaler-Rose test) and ten control sera were tested in latex agglutination. All RF-positive sera agglutinated latex particles coated with the different mammalian IgGs (cow, horse, human, mouse, sheep and rabbit) and with chicken anti-human C3 (which was used as a positive control), but none of them with non-specific chicken IgG. The control sera were all negative except when tested with chicken anti-human C3. Chicken antibodies should therefore be useful in assays were RF could interfere and give false positive reactions (e.g., nephelometry, latex agglutination or ELISA). PMID- 3351311 TI - The preparation of a new 57cobalt-labelled thyroxine for use in single/dual radioimmunoassay techniques. AB - The preparation of L-thyroxine labelled with 57cobalt for use as a second tracer in dual radioimmunoassay techniques for different biological molecules is described. The labelling procedure was monitored by paper chromatography and polyacrylamide gel electrophoresis; a yield of 42 +/- 10% (mean +/- 1 SD) was achieved in a total of 39 conjugation reactions. The method was optimized in terms of pH, reaction completion time, reactant concentration, and solubility of the tracer. A radioimmunoassay for thyroxine in human serum was developed utilizing this tracer, and this compared favorably with an established technique in which 125iodine was used as the tracer (n = 71, r = 0.91, y = 0.988 x - 1.93). PMID- 3351310 TI - Direct determination of molecular ratios of peptides coupled via N-succinimidyl 3 (2-pyridyldithio)propionate to carrier proteins using high performance liquid chromatography. AB - A simple, rapid and reproducible method is presented for direct determination of the substitution ratio of a carrier protein with a synthetic nonradioactively labeled peptide. The peptide was covalently linked by a thiol group of a cysteine residue to the immunogenic carrier protein using the heterobifunctional reagent N succinimidyl 3-(2-pyridyldithio)propionate. The substitution ratio was determined after reductive cleavage of the intermolecular disulfide bond between peptide and carrier and the amount of carrier and peptide quantitated directly by calibrated HPLC analysis within 15 min. PMID- 3351312 TI - Purification of mouse haptoglobin by antibody affinity chromatography and development of an ELISA to measure serum haptoglobin levels. AB - Mouse haptoglobin was isolated from acute-phase serum initially by affinity chromatography on haemoglobin-Sepharose. This proved inefficient, but sufficient material was obtained for use as an immunogen. Rabbit anti-haptoglobin antibodies were used as immunoabsorbents to isolate larger quantities of haptoglobin. Subsequently, specific anti-haptoglobin antibodies were prepared by affinity chromatography on haptoglobin-Sepharose. A direct sandwich ELISA for mouse serum haptoglobin was developed, using affinity purified reagents. The working range of the haptoglobin standard curve was 0.02-0.5 microgram/ml. The reagents did not cross-react with albumin or haemoglobin and the antibody also recognised rat haptoglobin. PMID- 3351313 TI - A new radiometric assay for the quantitation of surface-bound IgG on sensitized erythrocytes. AB - We have developed a sensitive, straightforward method for the quantitation of surface-bound IgG on sensitized erythrocytes. The assay is based on the consumption by sensitized cells of anti-IgG antiserum. The remaining anti-IgG is quantitated in a second incubation by precipitation with 125I-IgG in the presence of polyethylene glycol. Calibration curves for this assay were constructed using known amounts of unlabeled IgG. The method can be performed in microtitre plates and eliminates the use of purified anti-erythrocyte antibodies, or highly purified specific anti-IgG antisera. The results were completely consistent with those of immunofluorescence assays, but our method was much more sensitive, less than 500 molecules of IgG per cell being detected reproducibly. The technique is not laborious and takes much less time than previously described methods with similar sensitivity. As an example of the applicability of this test, the implications of ligand density for the detection by EA rosetting of Fc receptors on human monocytes are shown. The results suggest that a large variation exists in the affinity of the different types of Fc receptors for their ligands. PMID- 3351314 TI - Human AIDS and rabbit myxomatosis. PMID- 3351315 TI - Use of an in vitro model for studying the eradication of catheter colonisation by Staphylococcus epidermidis. AB - Silicone rubber catheters were experimentally colonised with three different strains of Staphylococcus epidermidis sensu stricto. The catheters were then perfused with brain-heart infusion broth by means of an in vitro apparatus which simulates the pharmacokinetics of intraventricular administration of antimicrobial agents. When colonisation was established, vancomycin was administered to the dosing chamber three times daily so as to give peak concentrations of 16, 32, 64 and 128 mg/l. Each experiment was performed in triplicate. Samples of fluid taken from each catheter were cultured before treatment and at intervals thereafter during perfusion for 4 weeks or until recolonisation became apparent. Those catheters not showing evidence of recolonisation were examined by scanning electron microscopy for the presence of organisms. Colonisation was eradicated (as judged by cultural examination) in 37% catheters but eradication did not bear any clear relationship to drug concentrations. Electron microscopical examination of all catheters showing eradication by cultural means revealed the presence of organisms. PMID- 3351316 TI - Disturbances of blood coagulation associated with Salmonella typhi infections. AB - Disturbances of blood coagulation were studied in 32 consecutive patients with typhoid fever on their admission to hospital. Estimations of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products (FDPs), factors VII, VIII and XII, alpha I antitrypsin, plasminogen, CI esterase inhibitor, and platelet counts were performed as well as liver function tests and blood counts. Five patients had laboratory evidence of disseminated intravascular coagulation (DIC) and two had a generalised bleeding disorder which in the other three was inapparent. The platelet count in the group as a whole was low (P less than 0.05) and the FDPs in most cases were mildly elevated. The pre-kallikrein values were depressed in three of the five with DIC, whereas factor XII was not reduced. These results indicate that bleeding disorders in typhoid fever are uncommon. The depression of pre-kallikrein indicates that the DIC is probably triggered by activation of the intrinsic coagulation pathway. Most patients had lymphopenia and monocytopenia but only two had neutropenia. PMID- 3351317 TI - Rat-bite fever in a gerbil breeder. AB - A case of rat-bite fever caused by Streptobacillus moniliformis in a gerbil breeder is described. Such a case has not been previously recorded. PMID- 3351318 TI - Rhodotorula rubra ventriculitis. AB - We describe a case of post-operative ventriculitis in an immunocompetent patient caused by an unusual organism, namely Rhodotorula rubra. The patient was treated successfully with antifungal agents. PMID- 3351320 TI - Persistent Legionella pneumophila bacteraemia in an immunocompromised host. PMID- 3351319 TI - Hospital transmission of multiply antibiotic-resistant Streptococcus pneumoniae. PMID- 3351321 TI - A case of septicaemia caused by Agrobacterium radiobacter. PMID- 3351322 TI - Frequency of human lymphocyte antigens in patients with brucellosis. PMID- 3351323 TI - Biomphalaria glabrata: influence of selected abiotic factors on leukocytosis. PMID- 3351324 TI - Life cycle of Amblyospora dyxenoides sp. nov. in the mosquito Culex annulirostris and the copepod Mesocyclops albicans. PMID- 3351325 TI - The insecticidal activity of cyclosporines on mosquito larvae. PMID- 3351326 TI - Tolypin, a new insecticidal metabolite of fungi of the genus Tolypocladium. PMID- 3351327 TI - PC 84, a parvo-like virus from the crab Carcinus mediterraneus: pathological aspects, ultrastructure of the agent, and first biochemical characterization. PMID- 3351328 TI - Incidence of patent infections of Anopheles quadrimaculatus (Diptera: Culicidae) larvae by Parathelohania anophelis (Protozoa: Microsporida) in rice fields in southwestern Louisiana. PMID- 3351329 TI - Ascorbic acid specifically increases type I and type III procollagen messenger RNA levels in human skin fibroblast. AB - In cultured human skin fibroblasts, ascorbic acid stimulates collagen production with no apparent change in the intracellular degradation of newly synthesized procollagen. To understand the basis for this effect, we measured the steady state levels of type I and type III procollagen mRNAs in cells treated with ascorbic acid. A three- to fourfold increase in collagen synthesis was associated with a two- to threefold increase in the levels of mRNAs for both type I and type III procollagens. These effects of ascorbic acid are explained by a translational control linked either to procollagen gene transcription or mRNA degradation. PMID- 3351330 TI - Skin granuloma formation in mice immunosuppressed by cyclosporine. AB - Granulomatous tissue reactions appear in athymic mouse skin, indicating that initiation of granuloma formation may be T-cell independent. To further evaluate the relationships between granuloma formation and T-cell function, we treated euthymic BALB/c mice with cyclosporine (Cs), a potent immunosuppressive drug, injected intramuscularly (150 mg/kg/day) 5 times a week. Hepatic granulomas were isolated from mice with schistosomiasis and transplanted into the skin of mice treated with Cs for 2 weeks. Cyclosporine injection was continued for 3 additional weeks. Blood levels of the drug increased during treatment (489 ng/ml at 2 weeks and 822 ng/ml at 5 weeks). Morphologically identical granulomas developed in both treated and untreated mice. Examination for T-cell functions showed that by the end of 2 weeks treatment, concanavalin A, phytohemagglutinin responses, and IL-2 activity were markedly depressed, and IL-2 receptor expression was not detected in either lymph nodes or spleen of the Cs-treated mice; however, after hepatic granuloma graft, T-cell functions in regional lymph nodes, but not in spleen, as well as peripheral blood eosinophilia were stimulated in Cs-treated mice. These data strongly suggest that intact T-cell activity is not essential for the initiation of granuloma formation. In addition, granuloma grafts appear to stimulate Cs-resistant T-cell activation locally, which amplifies and organizes the granulomatous response. PMID- 3351331 TI - Rapid diagnosis of sensitivity to ultraviolet light in fibroblasts from dermatologic disorders, with particular reference to xeroderma pigmentosum. AB - A rapid and simple method for determining the sensitivity of human fibroblasts to ultraviolet light is described. As an alternative to the colony formation assay, this method can be used for the rapid diagnosis of ultraviolet light sensitivity in fibroblasts from photosensitive disorders. The method is based on growth of small numbers of cells in 1-cm wells of culture trays for 4 or more days after irradiation and determination of cell survival by the incorporation of [3H]hypoxanthine. D37 values (the dose at which 37% of the control level of incorporation remains) obtained from this procedure showed the same relative sensitivity of normal and xeroderma pigmentosum fibroblasts as was obtained by colony formation. Untransformed and SV40-transformed fibroblasts, which have different growth rates and different responses to high cell densities, gave different D37 values by this assay in culture trays as compared with colony formation. Comparison of relative sensitivities to irradiation should therefore be made only between cell types with similar growth characteristics. The similar sensitivity of normal and xeroderma pigmentosum cells to mitomycin C was also determined by this culture tray method. By increasing cell density at the beginning of the experiments, a greater capacity of group C compared with group D fibroblasts for recovery from potentially lethal damage was also detected. PMID- 3351332 TI - Ontogeny of structural components at the dermal-epidermal junction in human embryonic and fetal skin: the appearance of anchoring fibrils and type VII collagen. AB - The ontogeny and composition of the dermal-epidermal junction (DEJ) in developing human embryonic and fetal skin was studied at progressive stages of gestation by immunofluorescence microscopy and immunocytochemistry using transmission electron microscopy (TEM). The DEJ of embryonic skin at 5 weeks estimated gestational age (EGA) was a simple basement membrane zone limited to the basal cell plasma membrane, lamina lucida, and lamina densa. A network of reticular collagen fibrils (reticular lamina) was deposited beneath the lamina densa by 6 weeks. Coincident with the onset of increased complexity in epidermal and dermal structure, at the time of the embryonic to fetal transition, the DEJ displayed additional components that were markers of maturation. At 7-8 weeks EGA, fine filamentous structures extended from the DEJ into the reticular lamina. By 9 weeks EGA hemidesmosomes and banded anchoring fibrils were recognizable, although distributed sparsely at the DEJ. With increasing gestational age, these structures displayed greater electron density and structural completeness. By the end of the first trimester, the DEJ appeared ultrastructurally similar to that of mature skin. Weak immunofluorescent labeling demonstrated the presence of type VII collagen at the DEJ by 8 weeks EGA. From 10-12 weeks EGA immunofluorescent labeling of the DEJ for type VII collagen was distinctly punctate, while immunoperoxidase labeling observed by TEM was linear, continuous, and sublamina densa in position. With ongoing gestation the immunofluorescent labeling became increasingly stronger at the DEJ. Thus, type VII collagen was present at the DEJ in the zone immediately beneath the lamina densa, before the appearance of mature anchoring fibrils but coordinate with the appearance of fine filamentous, unbanded structures, and appeared to increase with the development and accumulation of anchoring fibrils. PMID- 3351333 TI - Limitations of hairless mouse skin as a model for in vitro permeation studies through human skin: hydration damage. AB - Hairless mouse skin currently provides a popular model membrane for studies in human percutaneous absorption. Although some similarities between the two skin types have been demonstrated, the effects of prolonged hydration on hairless mouse skin have not previously been rigorously examined. We have measured in vitro the effects of hydration at 31 degrees C on the permeabilities of hairless mouse skin and human abdominal and scalp skin to a model polar compound (water) and a lipid material (hexanol). The permeability of hairless mouse skin rose dramatically, especially to water (fiftyfold increase), whereas the human skin was more stable. We also compared the effects of stripping the stratum corneum with the effects of 8-d hydration for hairless mouse and human abdominal skin. Hydration of hairless mouse skin was as effective as tape-stripping in eliminating the stratum corneum barrier, whereas stripping human skin was far more damaging than hydration, suggesting that prolonged hydration mechanically disrupted mouse skin but not human skin. Histological examination of fresh and hydrated tissues confirmed this suggestion. We therefore recommend that hairless mouse skin is not used as a model for human tissue during in vitro permeation studies under conditions of long-term hydration, i.e., greater than three days. PMID- 3351334 TI - Partial purification of plasma and tissue kallikreins in psoriatic epidermis. AB - Human psoriatic scale extracts produced kinins from heated plasma (11.3 +/- 5.5 ng kinin/mg protein) and from purified low molecular weight (LMW) bovine kininogen (4.4 +/- 1.7 ng/mg). Sephacryl S-200 gel filtration of the extracts showed three peaks of kininogenase activity with Mr values of 90,000 (K-I), 65,000 (K-II), and 35,000 (K-III). Upon DEAE-Sepharose chromatography of the Sephacryl peaks, K-I activity was found in the nonadsorbed fraction and formed kinins only from heated plasma. Peak K-II activity was resolved into two peaks, K IIa (in the nonadsorbed fraction), which formed kinins only from heated plasma, and K-IIb (in the adsorbed fraction), which formed kinins from both heated plasma and LMW bovine kininogen. K-III kininogenase activity appeared at the same position as K-IIb and also formed kinins from both substrates. Kininogenases K-I and K-IIa had the same Km value (0.3 mM) with Pro-Phe-Arg-p-nitroanilide(pNA), similar to that found with human plasma kallikrein. The Km value of K-IIb with Val-Leu-Arg-pNA (0.8 mM) was like that found for human salivary kallikrein, whereas K-III had a low affinity for this substrate. Like plasma kallikrein, K-I and K-IIa were inhibited by soybean trypsin inhibitor, but only weakly by aprotinin. In addition the kininogenase activity of both K-I and K-IIa was neutralized by adding antihuman prekallikrein immunoglobulin G (IgG). In contrast, K-IIb and K-III were strongly inhibited by aprotinin but not by soybean trypsin inhibitor, consistent with their being tissue kallikreins. It was confirmed that K-IIb and K-III shares antigenic determinant of urinary kallikrein. PMID- 3351335 TI - Altered leukocyte protein kinase activity in atopic dermatitis. AB - Previous studies have demonstrated elevated cyclic-AMP-specific phosphodiesterase (PDE) activity in mononuclear leukocytes (MNL) from patients with atopic dermatitis (AD). We questioned whether increased kinase activation could account for this observation. In these studies, we measured abnormally lower basal calcium/phospholipid-dependent protein kinase (PK-C) phosphorylation in MNL from patients with AD. Basal cAMP-dependent protein kinase (PK-A) phosphorylation was concomitantly higher in MNL from patients with AD. These results are in agreement with earlier reports that PK-A activity may have a negative influence on PK-C activity in certain cell systems. Stimulation with the H1-histamine agonist, thiazolylethylamine (TEA), of MNL from normal donors but not patients with AD, resulted in statistically significant increases in PK-C phosphorylation. This implies receptor down regulation or functional desensitization in AD cells. Altered basal protein kinase phosphorylation and abnormal response to selective histamine agonists seen in MNL from patients with AD could explain elevated PDE activity. PMID- 3351337 TI - Cyclosporin A does not inhibit epidermal growth at therapeutic levels. PMID- 3351336 TI - Comparison of hypothalamus-pituitary-adrenal axis suppression from superpotent topical steroids by standard endocrine function testing and gas chromatographic mass spectrometry. AB - We evaluated 38 males who had psoriasis vulgaris for evidence of hypothalamus pituitary-adrenal axis suppression (HPAS) during treatment with superpotent topical glucocorticosteroids. All men were treated with 49 g per week of either Betamethasone Diproprionate in an optimized vehicle or Clobetasol Proprionate ointment. Three methods used to assess HPAS were compared. Classic 8 a.m. plasma cortisol measurements, urinary-free cortisol, and 17-hydroxycorticosteroid determinations and gas chromatograph-mass spectrometry (GCMS) quantitation of urinary cortisol metabolites were compared. Values for all methods were obtained just prior to therapy and at days 4, 7, 14, and 21 during therapy and at day 28 after treatment was stopped for 7 d. Plasma cortisol measurements correlated well with other measures of HPAS. GCMS determination of urinary cortisol metabolites was slightly more sensitive at detecting HPAS than the other two methods. Persistent HPAS after day 7 was only appreciated by GCMS. Urinary-free cortisol and 17-hydroxycortisol was the least sensitive of the three methods. Analysis of urinary cortisol metabolites by GCMS may be most useful in the monitoring of HPAS resulting from use of topical glucocorticosteroid preparations. PMID- 3351338 TI - Epidermal calmodulin levels and reference variables. PMID- 3351339 TI - Cine MR: evaluation of cardiac ventricular function and valvular function. PMID- 3351340 TI - Cardiac function by magnetic resonance imaging. AB - Gated magnetic resonance imaging of the heart displays cardiac structures with excellent resolution. This ability should be useful for assessment of cardiac physiology where acquisition of systolic and diastolic images is required. In this study, left ventricular ejection fraction was determined in 50 patients from oblique long axis views of the left ventricle using the area length formula. Angulated views were obtained by electronic gradient angulation. For comparison, all patients had monoplane angiocardiography in the RAO position. Forty-five patients were also studied by radionuclide ventriculography. Ejection fractions determined by MRI and angiocardiography were closely correlated (r = 0.90). Correlation between MRI and radionuclide ventriculography was also acceptable (r = 0.79). In addition to global left ventricular function, MR images provide information about regional wall motion. In order to acquire a three-dimensional set of images at various phases of the cardiac cycle, shorter imaging times are mandatory. A new imaging technique with potential for functional studies uses low flip angles, short repetition times and gradient refocused echoes. Up to 40 images can be obtained within one cardiac cycle. When displayed in a looped fashion, visual assessment of cardiac motion, intracardiac blood flow, and systolic wall thickening is possible. Potential advantages of functional studies by MRI are the concomitant acquisition of anatomical information and the three dimensional frame of reference. PMID- 3351341 TI - Conventional computerized tomography of the heart. AB - Ungated cardio-CT provides good morphologic information in the case of congenital heart disease, volume or pressure loading, left ventricular aneurysm, tumours, thrombi, cardiac calcifications and pericardial diseases. It allows qualitative assessments of myocardial thickness and perfusion of coronary bypass grafts. ECG gated cardio-CT allows a quantitative assessment of systolic and diastolic myocardial thickness, volume calculation of cardiac cavities and evaluation of functional parameters. The correlation of the calculated left ventricular ejection fraction comparing laevocardiography and ECG-gated cardio-CT was poor (r = 0.7) mainly due to the comparable poor time resolution on the side of cardio-CT (approximately 0.1s). The quantitative analysis of regional wall motion based on cardio-CT showed for the diagnosis of pathologic wall motion a specificity of 80.5%, sensitivity of 73.9% and accuracy of 75.7%. Side effects must be taken into account following the injection of 200-250 ml hyperosmolar contrast medium during 5-10 minutes which causes intravascular fluid retention and cardiac volume loading. Patients prone to cardiac decompensation should be excluded from cardio CT examinations. PMID- 3351342 TI - The role of echocardiography and CT in the diagnosis of cardiac tumors. AB - A young male who presented with atypical chest pain was found to have a primary cardiac tumor. Chest X-ray, electrocardiogram, and echocardiographic findings can be nonspecific. Differential diagnosis and the role of different diagnostic modalities including echocardiogram, computerized tomography and magnetic resonance imaging are discussed. PMID- 3351343 TI - Five French versus eight French catheters and the Judkins technique. Advantages and limitations for studying coronary artery disease. AB - In order to compare 5 French versus 8 French catheters for assessing ischemic heart disease, we prospectively studied 2 groups of 100 patients each, one with 5 French (group I) and the other with 8 French (group II) catheters by the Judkins technique. Significant differences were found in the greater easiness to catheterize LV (p less than 0.05) and LCA (p = 0.01) in group II and in better quality image for LCA in group II (p less than 0.05), although all patients in both groups had acceptable image quality. Pressure curves quality was better in group II (p less than 0.01); X-ray exposure time was longer in group I (p less than 0.001) and arterial compression time in group II (p less than 0.0001). Group I showed 3 and group II 10 mild hematomas (p less than 0.05). The procedure could be completed by the elected first artery and type of catheter in 95 patients in group I and in 96 in group II. Thus, the Judkins technique with 5 French catheters is as valid as with 8 French for assessing ischemic patients, reducing arterial morbidity, although mildly increasing technical difficulty and mildly decreasing quality image. PMID- 3351344 TI - A comparison of morphine administered by patient-controlled analgesia and regularly scheduled intramuscular injection in severe, postoperative pain. PMID- 3351345 TI - Multidimensional measurement of cancer pain: comparisons of US and Vietnamese patients. PMID- 3351346 TI - The etiology, evaluation and treatment of head and facial pain in the elderly. PMID- 3351348 TI - The use of methadone in opioid-tolerant patients. PMID- 3351347 TI - The relief of body wall pain secondary to malignant hepatic metastases by intercostal nerve block with bupivacaine and methylprednisolone. PMID- 3351349 TI - Douleur a deux. PMID- 3351350 TI - Asthenia in patients with advanced cancer. Issues in symptom control. Part 1. PMID- 3351351 TI - Ultrastructural aspects of in vitro fertilization in sheep. AB - Fertilization events of the sheep oocyte have been analyzed by electron microscopy. In the fertilization cone, near the decondensing sperm nucleus, several areas composed of electron-dense filamentous material (FA) were observed. Moreover aster-like structures were present in the vicinity of the sperm neck and proximal midpiece. During swelling of the pronuclei, redistribution of cytoplasmic organelles occurred near the male pronucleus in a region facing the center of the egg. In this region, containing the sperm midpiece, large aggregates of Golgi complexes and cisternae of endoplasmic reticulum were associated with FA, microtubule foci, and abundant microtubules, suggesting cytaster formation. This complex migrated with the male pronucleus and the proximal sperm midpiece toward the center of the egg. A potential role of these subcellular structures, in the process of pronuclear migration, is proposed. PMID- 3351352 TI - Reaggregation behavior of different types of collagen in vitro: variations in the occurrence and structure of dimeric segment long-spacing collagen. AB - Segment long-spacing collagen (SLS) can be precipitated from solutions of collagen using ATP as the inducing agent. Dimeric SLS aggregates have been observed in addition to monomeric SLS. We have compared collagen types I, II, III, and V with respect to their ability to form dimeric SLS in vitro. These collagen types were isolated from bovine tissues and characterized by polyacrylamide slab gel electrophoresis of the respective alpha-chains. Only monomeric SLS can be detected in preparations of collagen types I and III. Dimeric SLS, on the other hand, accounts for the majority of the crystallites seen in preparations of collagen types II and V. Dimeric SLS from both collagen types II and V reveal overlap zones at the carboxy-terminal ends of the collagen molecules. However, dimeric SLS from collagen types II and V differ with respect to their overlap distances. Significant portions of the triple helical domains of collagen molecules are occupied by the overlap region of dimeric SLS from type II collagen. On the other hand, dimeric SLS from type V collagen is composed of molecules overlapping only at their short nonhelical telopeptides. It is concluded that the ability of collagen molecules to aggregate into dimeric SLS under defined experimental conditions is collagen type dependent. PMID- 3351353 TI - An electron microscopic and spectroscopic study of murine epiphyseal cartilage: analysis of fine structure and matrix vesicles preserved by slam freezing and freeze substitution. AB - Newborn mice epiphyseal growth plates were preserved by slam freezing/freeze substitution and examined by conventional electron microscopy, stereopsis, high voltage electron microscopy, and electron spectroscopic imaging (ESI). To illustrate the improved ultrastructure of this cryogenic procedure, conventional, aqueously fixed growth plates were included showing collapsed hypertrophic chondrocytes surrounded by a depleted and condensed extracellular matrix. In contrast, the cryogenically prepared epiphyses contain chondrocytes and extracellular matrix vesicles both in direct contact with proteoglycan filaments retained in an expanded state. ESI is an electron microscopic technique which enables the direct localization of atomic elements superimposed over fine structural details. This technique was used to examine the colocalization of calcium and phosphorus within matrix vesicles and within their associated extracellular environments. Matrix vesicles appeared in three distinct diameter ranges. The integrity of the matrix vesicles was examined at various stages of mineralization and also within the mineralized zone of provisional calcification. PMID- 3351354 TI - Conservation of tubulin alpha-beta differences in zinc-induced sheets with variations in pH and microtubule-associated protein content. AB - Zinc-induced tubulin sheets were grown at pH values of 5.7 and 6.4 from porcine brain tubulin purified by phosphocellulose chromatography as well as from microtubule protein containing tubulin plus 20% (w/w) unfractionated microtubule associated proteins (MAPs). Electron micrographs of negatively stained sheets were analyzed by a combination of real space cross-correlation and Fourier space methods, providing two-dimensional reconstructions to approximately 16 A resolution. The reconstructed images revealed that the protofilaments comprising zinc-induced sheets are composed of two clearly distinguishable alternating subunits, presumably corresponding to the alpha- and beta-tubulin monomers, whose morphologies are not significantly influenced by pH or the presence of MAPs during sheet assembly. Sheets assembled at pH 5.7, either with or without MAPs, were divided into two domains by a protofilament discontinuity which was not present in sheets assembled at pH 6.4, and displayed a 2.4 A reduction of the interprotofilament distance in projection relative to sheets assembled at pH 6.4. We conclude that morphological differences between tubulin subunits represent intrinsic structural features not contributed by MAPs, and that pH is more important than MAP content in influencing the lattice parameters of zinc-induced sheets. PMID- 3351355 TI - Molecular morphology of fibrin monomers and early oligomers during fibrin polymerization. AB - The structural features of early fibrin oligomers produced during the initial stages of polymerization were investigated by rotatory shadowing after cryotechnical preparation. The building blocks of polymerization, namely fibrin monomer units (in analogy to fibrinogen itself), were found to exhibit a high degree of flexibility which is independent of fibrinopeptide A and B removal. Early polymers exhibited directed longitudinal growth and were frequently branched. Along the main oligomer axis, fibrin monomer units were randomly orientated. Within early oligomers, a given fibrin monomer unit was found to establish a single contact with each of its two neighbors, suggesting that during the early stages of polymerization, only one polymerization and one binding site are activated per fibrinogen molecule (becoming an AB2 fibrin monomer unit). This morphological feature was corroborated by the finding that early oligomer fractions are deficient in only 50% of releasable fibrinopeptide A. Early associations between AB2 fibrin monomer units were demonstrated to be reversible and to occur in the absence of direct domainal contact; interactions thus presumably occur via fine molecular protrusions on either D or E domains. The arrangement of AB2 fibrin monomer units within early oligomers suggests that, with respect to their structural organization, fibrinogen molecules are radially symmetrical through the E domain (implying an antiparallel organization of polymerization and binding sites). This pattern is inconsistent with a "top bottom" model, and thus with "half-staggered double-stranded" polymer growth. The methodological problems responsible for the apparent conflict with previous morphological findings are discussed. PMID- 3351356 TI - Spermatozoon ultrastructure of Platichthys flesus. AB - The ultrastructure of the spermatozoon of Platichthys flesus (flounder) has been determined. The cell is of the primitive type and lacks an acrosome. The bullet shaped, homogeneously electron-dense nucleus has a deep, caudal articular fossa containing proximal and distal centrioles. Both centrioles are embedded in pericentriolar material which is intimately associated with the nuclear envelope. Around the proximal centriole the material is organised into a dense ring which bears nine fibres associated with the triplets, and a large fibrous body, all connected to the nuclear envelope. Connections exist also between the pericentriolar material of the proximal and distal centrioles. The material around the distal centriole is organised into a complex collar. The anterior surfaces of eight spherical mitochondria lie within shallow depressions of the nuclear caudal surface. They form a ring surrounding the posterior opening of the articular fossa and the proximal region of the 9 + 2 flagellar axoneme. PMID- 3351357 TI - Spermiogenesis in Platichthys flesus. AB - Early spermatids of Platichthys flesus (flounder) have a central spherical nucleus and cytoplasm with numerous dispersed mitochondria and a pair of peripheral centrioles. One of the centrioles acts as a kinetosome for axoneme formation. After the start of chromatin condensation the centrioles and developing axoneme migrate to adopt a tangential orientation adjacent to a flattened, lateral margin of the nucleus. During migration, pericentriolar material becomes reorganised. The proximal centriole becomes surrounded by nine fibres, and the distal centriole by a complex collar. As the nucleus condenses it undergoes a rotation which shifts it to the anterior of the centrioles and deepens the articular fossa which houses, and is connected to, the two centrioles and their associated structures. This rotation also results in the mitochondria becoming relocated to form a ring around the proximal region of the axoneme to give the cell its mature ultrastructure. PMID- 3351358 TI - Microtubules in the spermatids of stick insects. AB - Spermatids from two phasmid species were seen to possess an unusually large amount of microtubules along the nucleus and tail. Some of the microtubules have a loosely fitting sleeve for half a micron or more. During late stages in spermiogenesis the microtubules aggregate and form one or several "microtubular crystals" consisting of electron-lucid tubular elements with a diameter of about 360 A. The tail flagellum contains five kinds of microtubular structures, which all have a substructure of longitudinal protofilaments that is clearly visible after fixation in the presence of tannic acid. The so-called accessory tubules have 17 protofilaments that have the same appearance as that in ordinary, 13-unit microtubules, but are somewhat thicker than those. It is evident that the protofilaments in both the 17-unit and the 13-unit microtubules run parallel or nearly parallel to the long axis of the microtubules. It is of interest that both types of microtubules possess a prime number of protofilaments which may give the fagellum certain functional advantages. PMID- 3351360 TI - [Current state of IVF and GIFT]. PMID- 3351359 TI - [A basic study on cervical ripening--with special reference to the stretch modulus in the rat uterine cervix]. AB - To study the physiological factors in cervical ripening, we analyzed static stress-strain diagrams of experiments done on cervical tissue from Wistar rats. The measured strips (N = 220) were stretched at a given increasing tension while the length and tension were continuously recorded. The data obtained were converted to a stress-strain relationship and the following results were obtained: 1. The average stretch moduli for nonpregnant, term and puerperal rats were 466.91 +/- 129.95 x 10(3) mgw/mm2, 9.80 +/- 1.26 x 10(3) mgw/mm2 and 29.76 +/- 5.78 x 10(3) mgw/mm2 (mean +/- S.E.) respectively. 2. The yield and break points were lowest in rats at labor. 3. Succeeding two or several repetitions of loading and unloading of cervical tissue samples revealed a reduction in their stiffness. 4. The cervical tissue samples were pulled after adding PGF2 alpha, PGE1, PGE2, DHA-S etc., and the results of these experiments indicate that some of these drugs had the effect of elongating the strain at the beginning of the linear portion and the effect of changing cervical contractions. 5. DHA-S or its metabolites except estradiol might have a direct effect on the dilatation of the rat cervix. 6. Microscopically detected edema in the term specimen suggested collagen dispersion. PMID- 3351361 TI - [Ovarian function and body weight]. PMID- 3351362 TI - [Situs inversus with cleft lip--a case report]. PMID- 3351364 TI - [Determination and clinical application of the lecithin/sphingomyelin ratio in amniotic fluid by high performance liquid chromatography]. AB - The lecithin/sphingomyelin (L/S) ratios in standard solution and amniotic fluid of 64 pregnant women were measured by high performance liquid chromatography (HPLC). The procedure is highly accurate, and the correlation coefficient between the HPLC value and standard solution was 0.984. The regression line was: Y = 0.8X + 0.17 (Y: standard solution X: HPLC values). In 64 pregnant women, 41 cases were delivered within 72 hrs of the amniotic fluid collection. The prediction of respiratory distress syndrome (RDS) was performed with variables of the L/S ratio less than 4.20. 8 of 9 babies (88.9% of sensitivity) who developed RDS and 3 of 3 (100% of sensitivity) other types of respiratory failure due to hydrothorax were predicted by this method. In conclusion, this method is simple, rapid and sensitive for the prediction of respiratory distress syndrome and other respiratory failure. PMID- 3351363 TI - [Changes in human serum corticosterone and cortisol during pregnancy, labor and delivery]. AB - Serum corticosterone and cortisol concentrations were determined during pregnancy and at delivery in six normal pregnant women. The concentrations of both steroids increased gradually during pregnancy and in late pregnancy they reached values which were 2.5 times those in early pregnancy. The corticosterone concentration increased rapidly immediately after delivery, the values averaging 6.3 times those at the onset of the first labor pain, whereas the cortisol concentration was only about 2.1 times. Although the corticosterone to cortisol concentration ratio was constantly within the normal range throughout pregnancy until delivery, a significant increase in the ratio was observed immediately after delivery (p less than 0.001). It has been known that adrenal secretion of corticosterone in response to exogenous ACTH occurs prior to that of cortisol. Consequently, our results suggest that the dramatic increase in the corticosterone serum concentration after delivery may be due to some physical stress in terms of labor pains, while the steady increase before labor must be due to physiological organic changes characteristic of pregnancy. PMID- 3351365 TI - [Coagulation-fibrinolysis and kinin-forming systems in toxemia of pregnancy]. AB - The changes in the coagulation-fibrinolytic system and kinin-forming system in toxemia of pregnancy were studied to clarify the relationship between the hemostatic system and severity of toxemia. The results obtained were as follows: 1) Both activity and antigen of antithrombin III (AT-III) and Factor XIII in toxemia of pregnancy were significantly lower than those of normal pregnancy, and became lower as the severity of toxemia increased. In particular, a significant negative correlation was observed between the total score for the gestosis index (G.I) and AT-III activity (r = -0.447, p less than 0.005). These results reveal that AT-III is not only a sensitive indicator of the hypercoagulable state but also a useful indicator of the severity of toxemia. 2) Plasma prekallikrein in toxemia became much lower, and bradykinin in toxemia became much higher than those of normal pregnancy. These results mean that there was not only activation of the coagulo-fibrinolytic system but also activation of the kinin-forming system in toxemia. 3) The plasmin-alpha 2-plasmin inhibitor complex in toxemia was significantly greater than that in normal pregnancy (p less than 0.001), and became very high as the severity of toxemia increased (p less than 0.05). In the mild toxemia group, the plasmin-alpha 2-plasmin inhibitor complex became greater as AT-III decreased and a significant negative correlation was observed (r = 0.59, p less than 0.05), whereas in severe toxemia, the complex did not increase as AT-III decreased and no correlation could be observed. These results show that in toxemia of pregnancy, the coagulation system dominates the fibrinolytic system as severity of toxemia increases. PMID- 3351366 TI - [Potentiation of the antitumor effect of cisplatin by calmodulin antagonists (W-7 and W-5) in nude mice bearing human ovarian carcinoma]. AB - The present study was designed to potentiate the antitumor effects of cisplatin by combination with calmodulin antagonists (W-7 and W-5) by using nude mice bearing human ovarian carcinoma. Tumor growth in nude mice treated with W-7 or W 5 combined with cisplatin was significantly inhibited, compared to that in nude mice treated with W-7 alone, W-5 alone or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of the spleen cells from tumor bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in the survival time among untreated, cisplatin-treated, W-7-treated and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5, a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin was observed with respect to inhibition of the tumor growth as well as prolongation of the survival time. PMID- 3351367 TI - The confirmation of norethindrone aromatization in primary human hepatocytes by the Vitafiber-II cell culture system. AB - A portion of norethindrone (17 alpha-ethynyl-19-nortestosterone) was confirmed to be aromatized to ethynyl estradiol (17 alpha-ethynyl estradiol) in primary human hepatocytes cultured using the Vitafiber-II cell culture system. PMID- 3351368 TI - [The influence of gestational edema on maternal and perinatal outcome]. AB - In order to detect the influence of edema on maternal and perinatal outcome, 1,326 records of pregnant women without vascular nor renal diseases who were delivered of single infants were reviewed. The results were as follows. 1. Edema was observed in 214 of 1,326 subjects (16%). 2. In subjects with edema, 86% in primipara and 97% in multipara had no additional signs of preeclampsia subsequently during pregnancy and postpartum. 3. In thirteen subjects with edema before 28 weeks of gestation, five subjects (38.5%) had additional signs of preeclampsia subsequently and four developed severe preeclampsia. In 201 subjects with edema after 28 weeks of gestation, fourteen subjects (7%) had additional signs of preeclampsia subsequently and only one woman developed severe preeclampsia. 4. Mean birth weights in subjects with edema were significantly higher than that in subjects without edema in primipara. But, among the other parameters, no significant difference was found. These results indicate that edema by itself does not affect the maternal and perinatal outcome. However, the onset of edema before 28 weeks of gestation may be a useful sign to predict the onset of hypertension and proteinuria. PMID- 3351369 TI - [Reconstruction of the endometrium using the collagen membrane]. PMID- 3351370 TI - Keys to the successful implementation of an ICU patient data management system. AB - Implementation of an ICU data management system requires consideration of many factors, including site preparation for equipment, system backup, ICU & medical staff training and evaluation. This paper describes the strategy for implementing a patient data management system at Cedars-Sinai Medical Center and details our steps for planning, training, configuration and problem resolution. PMID- 3351371 TI - A new intensive care worksheet. AB - This article presents a new manual daily worksheet for recording data on a patient's status in an Intensive Care Unit. It permits a rapid view of the whole picture of the patient's condition at a certain hour since the system of recording is based on the time an event happened. Only one single page is used for each day. Space is provided for essential data, ventilatory parameters, laboratory results, fluid balance, drug therapy and special treatments. Attended staff, invited consultants as well as nurses add written notes which complete the picture provided by numbers. It does not replace the computerized interpretation, statistical analysis or storage of data, but it comes as an easy-to-use daily tool at the bedside. PMID- 3351372 TI - Phase space electroencephalography (EEG): a new mode of intraoperative EEG analysis. AB - Intraoperative monitoring of electroencephalography (EEG) data can help assess brain integrity and/or depth of anesthesia. We demonstrate a computer generated technique which provides a visually robust display of EEG data plotted as 'phase space trajectories' and a mathematically derived parameter ('dimensionality') which may correlate with depth of anesthesia. Application of nonlinear mathematical analysis, used to describe complex dynamical systems, can characterize 'phase space' EEG patterns by identifying attractors (geometrical patterns in phase space corresponding to specific ordered EEG data subjects) and by quantifying the degree of order and chaos (calculation of dimensionality). Dimensionality calculations describe the degree of complexity in a signal and may generate a clinically useful univariate EEG descriptor of anesthetic depth. In this paper we describe and demonstrate phase space trajectories generated for sine waves, mixtures of sine waves, and white noise (random chaotic events). We also present EEG phase space trajectories and dimensionality calculations from a patient undergoing surgery and general anesthesia in 3 recognizable states: awake, anesthetized, and burst suppression. Phase space trajectories of the three states are visually distinguishable, and dimensionality calculations indicate that EEG progresses from 'chaos' (awake) to progressively more 'ordered' attractors (anesthetized and burst suppression). PMID- 3351373 TI - A 32 key keyboard for the HP PDMS. AB - The keyboard remains the primary human interface device for existing patient data management systems. The standard bedside keyboard for the Hewlett-Packard PDMS has 16 keys which are used for both numeric data entry and multiple functions, accessed by shift key combinations. We have designed and constructed a 32 key keyboard which speeds single keystroke access to all PDMS functions. The new keyboard is backwards compatible and requires no PDMS software changes. A 32 key keyboard offers many advantages for use with the HP PDMS. The device presented is backwards compatible with the vendor's keyboard and requires no software changes. This keyboard could serve as an updated functional replacement for thousands of keyboards now in use. PMID- 3351374 TI - Using word processor text files as an active bibliography. AB - Data base systems for microcomputers are generally available. Most are reasonable priced and easy to use. Their disadvantages are restrictions placed on the amount of data stored in a single field, and the output format--usually tabular or label in style. This article describes the use of word processor text files as a data base allowing search and retrieval, with special reference to abstracting and storage of literature citations. Size of text entry and ultimate output format are extremely flexible using this method. PMID- 3351375 TI - Postoperative monitoring of conjunctival oxygen tension and temperature. AB - To define the utility of conjunctival temperature (Tcj) and conjunctival oxygen tension (PcjO2) monitoring during rewarming in the postoperative period, we measured serial Tcj, PcjO2 and PcjO2 index (PcjO2/PaO2) values in 10 patients after cardiac surgery. PcjO2 and PcjO2 index were markedly depressed at the low conjunctival temperatures recorded during the immediate postoperative period. As the patients' core and conjunctival temperatures increased, there was a concomitant, linear increase in PcjO2 and PcjO2 index for Tcj less than 33.5 degrees C. Two patients showed deviation from this temperature-related rise in PcjO2 and PcjO2 index, and both of these patients demonstrated physiologic deterioration associated with cardiac arrest or hypotension. These results indicate that monitoring of PcjO2 and Tcj can provide a continuous assessment of the adequacy of peripheral perfusion and oxygenation in the postoperative period. PMID- 3351376 TI - Portable computers used for respiratory care charting. AB - We studied the feasibility of using a portable lap computer (PLC) for bedside documentation of respiratory care procedures. Three Radio Shack TRS-80 Model 100 (PLCs) were used to capture and transfer the charting by phone into the hospital information system (HIS). Charting on the PLC could be done anywhere at the convenience of the therapist. Transferring data from the PLC to the HIS could be accomplished from any patient room, since all had phone jacks. Once information was entered into the HIS, it became immediately available for review on all nursing station terminals. A 39-day study of 5,019 entries was conducted using 12 therapists of whom 6 were randomly selected to carry PLCs and the other 6 used conventional ward terminals. We found that: 1) There was no statistically significant difference between PLC and nursing terminal entry in productivity or promptness of reporting; 2) Ward terminals were generally available for entry; 3) Cost, maintenance, initial training required, and therapist preference favored ward entry. We conclude that a PLC can be used in a clinical setting as a means of collecting and reporting data from the bedside, and as an input device to a larger computer system, but offers considerable disadvantages in comparison to entry at conventional terminals on the HIS if they are readily accessible. PMID- 3351377 TI - Relationship between membrane depolarization and extracellular calcium influx during neutrophil activation. AB - To better define the relationship between membrane depolarization and extracellular Ca2+ influx during neutrophil activation, we compared stimulation by elevating the extracellular K+ concentration, [K+]o, with stimulation by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP). Elevation of [K+]o resulted in uniform depolarization of the entire population of cells. This was associated with an influx of Ca2+ that was temporally delayed and quantitatively less than that induced by fMLP. K+ depolarization also caused increased expression of type 1 (C3b/C4b) complement receptor (CR1) and type 3 (C3bi) complement receptor (CR3), but the increments were less than with fMLP. We then used pertussis toxin to determine if guanosine triphosphate (GTP)-binding proteins were involved in these responses. Toxin inhibited the fMLP-induced membrane depolarization as well as the uptake of extracellular Ca2+ and the expression of both CR1 and CR3 induced by the chemoattractant. This indicates that the fMLP receptor is not directly coupled to an ion channel. The membrane depolarization induced by elevating [K+]o was not inhibited by toxin, but the uptake of Ca2+ and the increased expression of CR1 and CR3 were all significantly inhibited. The toxin failed to block increased CR1 and CR3 expression induced by ionomycin, demonstrating that its effects were not attributable to general toxicity. The results suggest that voltage gating is not the major mechanism by which polymorphonuclear leukocytes (PMNs) increase their permeability to extracellular Ca2+. Initial signals, whether generated by chemoattractants binding to their receptors or by small initial influxes of extracellular Ca2+, must be amplified by pertussis toxin-sensitive steps to fully increase the Ca2+ permeability and optimally activate the cell. PMID- 3351378 TI - Gaucher-like changes in human blood-derived macrophages induced by beta glucocerebrosidase inhibition. AB - Human blood-derived macrophages were cultured in the presence of conduritol-B epoxide, a specific inhibitor of beta-glucosidase, to induce changes resembling those occurring in the cells of patients with Gaucher's disease. After 24 hours of incubation, only 5% of the original beta-glucosidase activity remained; on removal of the inhibitor, the enzyme activity recovered almost fully to control levels after 5 days. After 30 days of incubation with conduritol-B-epoxide, the macrophages contained almost 10 times as much glucocerebroside as the untreated controls, and the cells displayed morphologic changes reminiscent of Gaucher's cells. This in vitro system may enable detailed studies on the pathogenetic mechanisms associated with glucocerebroside accumulation in human macrophages as well as on the turnover of the accumulated substrate and reversal of the morphologic abnormalities on removal of the inhibitor. PMID- 3351380 TI - Factor VII activity state in coronary artery disease. AB - In a recent study, Dalaker et al. (Br J Haematol 1985; 61:315-22) reported that men at high risk for cardiovascular disease had an increased mean level of factor VII procoagulant activity that was apparently attributable to an increase of a phospholipase C-sensitive form of factor VII in their plasma. We chose to investigate this phenomenon further by observing patients at high risk of coronary artery disease with assays that reflect the activity state of factor VII. We measured factor VII levels in patients before coronary arteriography and in normal subjects by an amidolytic assay (FVIIam assay) and by a standard clotting assay (FVIIc-A assay), both of which reflect the total amount of factor VII and are insensitive to activated factor VII, and by the method of Seligson et al. (Blood 1978;52:978-88) (FVIIc-B assay), which is sensitive to the presence of activated factor VII. In the FVIIc-A and FVIIam assays, the patients had a significantly higher mean value than the normal subjects; in the FVIIc-B assay, the patients had a significantly lower mean value than did the normal subjects. Moreover, the ratio of FVIIc-B to FVIIam, which is an indicator of the factor VII activity state, was much lower for the patients (0.70) than for the normal subjects (0.99). Thus, patients at high risk for coronary artery disease have an increased mean level of total factor VII that is not associated with an increase in activated factor VII and therefore presumably reflects an increase in zymogen factor VII. PMID- 3351379 TI - Hyperoxic lung injury in mice: effect of neutrophil depletion and food deprivation. AB - Conflicting data exist on the role of neutrophils (PMNs) in the pathogenesis of hyperoxic lung damage. We examined the contribution of PMNs and the contribution of food deprivation, a frequent complication of the methods used to produced neutropenia, to the lung damage that results when mice are exposed to high concentrations of oxygen. Mice were exposed to either 100% oxygen or air for up to 4 days. Neutropenia was induced by a single tail vein injection of nitrogen mustard (NM) given 1 day before the oxygen exposure. Food deprivation, which induced the same weight loss as that found in NM-treated mice, was achieved by withholding food (fasted) during the oxygen exposure. We examined mortality; weight loss; bronchoalveolar lavage (BAL fluid) protein concentration, cell count, and differential count; the number of PMNs in blood; and lung histologic conditions by light and electron microscopy. NM-treated mice lost approximately 25% of their body weight when exposed to either air or oxygen. They also had more severe lung damage than the saline-treated mice during hyperoxic exposure, despite a marked reduction in the number of PMNs in blood, BAL fluid, and lung tissue. Although a correlation was found between the number of blood PMNs and the BAL protein concentration in the nonneutropenic mice (r = 0.69; P less than 0.001), no correlation was seen in the neutropenic mice (r = 0.26). Fasted, oxygen-exposed mice had the same weight loss as the NM mice, but they had more severe lung damage at an earlier time (day 3 vs. day 4) and greater mortality than the saline-treated and the NM-treated mice. These results indicate that PMNs are not required for either the development or progression of hyperoxic lung damage in mice; fasting increases susceptibility to the lung damage; and differences in nutritional status may explain, in part, the controversial role of PMNs in oxygen-induced lung damage. PMID- 3351381 TI - Vision therapy. PMID- 3351382 TI - Enriching language learning environments for students with learning disabilities. PMID- 3351383 TI - The relationship between parents' socioeconomic status and education level, and adult occupational and educational achievement of children with learning disabilities. PMID- 3351384 TI - Reading and writing competencies of adolescents with learning disabilities. PMID- 3351385 TI - Coping strategies of university students with learning disabilities. PMID- 3351386 TI - Narrative abilities of children with learning disabilities and nondisabled children: story structure, cohesion, and propositions. PMID- 3351387 TI - Self-concept and success-failure attributions of nonhandicapped students and students with learning disabilities. PMID- 3351388 TI - Performance of nondisabled adults and adults with learning disabilities on a computerized multiphasic cognitive memory battery. PMID- 3351389 TI - Early identification of learning disabilities using the Meeting Street School Screening Test. PMID- 3351390 TI - Similarities and differences between parents' and teachers' observations of the behavior of children with learning problems. PMID- 3351391 TI - Epidemiological models for sexually transmitted diseases. AB - The classical models for sexually transmitted infections assume homogeneous mixing either between all males and females or between certain subgroups of males and females with heterogeneous contact rates. This implies that everybody is all the time at risk of acquiring an infection. These models ignore the fact that the formation of a pair of two susceptibles renders them in a sense temporarily immune to infection as long as the partners do not separate and have no contacts with other partners. The present paper takes into account the phenomenon of pair formation by introducing explicitly a pairing rate and a separation rate. The infection transmission dynamics depends on the contact rate within a pair and the duration of a partnership. It turns out that endemic equilibria can only exist if the separation rate is sufficiently large in order to ensure the necessary number of sexual partners. The classical models are recovered if one lets the separation rate tend to infinity. PMID- 3351392 TI - Induced electric and magnetic fields due to wave propagation in a tubular bone. AB - Electric and magnetic fields in tubular bones induced due to the propagation of travelling axisymmetric torsional waves, are determined in the paper by accounting for the piezoelectricity, inhomogeneity and anisotropy of osseous tissues. Using the derived expressions and experimentally determined values of the involved physical constants, numerical values of the displacement and stress fields, and also the induced fields are computed for points at different locations of the bone specimen. PMID- 3351393 TI - Size adaptation of Turing prepatterns. AB - Spontaneous pattern formation may arise in biological systems as primary and secondary bifurcations to nonlinear parabolic partial differential equations describing chemical reaction-diffusion systems. Such Turing prepatterns have a specified geometry as long as D/R2 (the diffusion coefficient of the morphogen D divided by the square of a characteristic length) is confined to a (usually) limited interval. As real biochemical systems like cleaving eggs or early embryos vary considerably in size, Turing prepatterns are unable to maintain a specified prepattern-geometry, unless D/R2 is varied as well. We show, that actual biochemical control systems may vary Dapp/R2, where Dapp (kappa) is an apparent diffusion constant, dependent on enzyme regulated rate constants, and that such simple control systems allow Turing structures to adapt to size variations of at least a factor 10(3) (linearly), not only in large connected cell systems, but in single cells as well. PMID- 3351395 TI - Calculation of the inbreeding coefficient. AB - Wright's rule for calculating the inbreeding coefficient for an arbitrary pedigree is proven for both autosomal and X-linked loci. PMID- 3351394 TI - On the formation of circulating patterns of excitation in anisotropic excitable media. AB - We present a model of excitable media with the feature that it has a vulnerable phase during which a premature current stimulus will result in the formation of a reentrant self-sustained wave of excitation. The model exploits anisotropic coupling of identical cells, and is therefore useful as a model for the myocardium. We give rigorous verification that there is a vulnerable phase, and demonstrate numerically that permanently rotating waves are formed. Finally, it is shown that the direction of fastest propagation in myocardium is not necessarily the direction of highest safety factor, contrary to commonly accepted opinion. PMID- 3351396 TI - Toward a common language. PMID- 3351397 TI - Potential impact of colonic irrigation on the indigenous intestinal microflora. AB - Under normal physiological conditions, the indigenous intestinal microflora is stable. The stability protects the host from colonization of nonindigenous microorganisms, including pathogens. Indigenous microorganisms capable of producing toxins are held in check by competing microflora, but any accidentally absorbed toxins are efficiently detoxified by the liver in the absence of hepatic pathology. Antibiotics are known to disrupt the normal flora leading to increased susceptibility to infection with other members of the normal flora or to toxins produced by them. It is possible that mechanical disruption of the flora by colonic irrigation could have a similar effect. Inadequately disinfected colonic irrigation machines have been the source of documented iatrogenic infection with Entamoeba histolytica. The potential for iatrogenic transmission of AIDS in a similar fashion must be considered. PMID- 3351398 TI - Organ-specific dosimetry in spinal radiography: an analysis of genetic and somatic effects. AB - Radiation doses absorbed by the uterus, ovary, testicle and active bone marrow are computed for cervical, thoracic, lumbar, full spine and chest series performed under typical office conditions. Assuming a nonthreshold, linear relationship between dose and radiogenic effect, the computed tissue-specific doses are used to estimate the probability that each X-ray series might enhance the statistical probability of occurrence of an adult leukemia fatality of the irradiated patient; a childhood leukemia, mental retardation or cancer fatality as a result of fetal irradiation; or a variety of sex cell chromosomal aberrations in irradiated patients. It is concluded that the greatest hazard to active bone marrow, the uterus and the gonads is posed by lumbar and full spine radiography and that the need to adequately justify such exposure is mandatory; furthermore, in these series, irradiation of the ovary is 10 times as great as that of the testicle. Lumbar radiographic examinations can be made significantly safer by the elimination of the lumbosacral spot view. PMID- 3351399 TI - Proteoglycans and degenerative spondylosis. AB - Proteoglycans are high molecular weight glycoproteins found in connective tissue. They imbibe water into intervertebral disc and apophyseal joint articular cartilage, endowing the tissues with elasticity and compressibility. A decrease in total tissue content of proteoglycans appears to predispose intervertebral disc to degeneration. The earliest tissue changes associated with the onset of spondylosis occur at the molecular level and may include alterations in proteoglycan structure and content. A number of models have been suggested to describe the relationship between changes in proteoglycan composition and degenerative changes in cartilage and intervertebral disc. PMID- 3351400 TI - Hass' disease. AB - A case of posttraumatic avascular necrosis of the humeral head (Hass' disease) is presented along with serial radiographs taken over a period of 4 1/2 y. The favorable response to conservative physical therapies is described. PMID- 3351401 TI - Examiner error in leg length measurement. PMID- 3351402 TI - Traumatic radial head subluxation in young children: a case report. PMID- 3351403 TI - Inter- and intra-examiner reliability of motion palpation for the thoracolumbar spine. PMID- 3351404 TI - A critical study of the student interns' practice activities in a chiropractic college teaching clinic. PMID- 3351405 TI - Dietary control of mild essential hypertension. PMID- 3351406 TI - Newer data on the configuration and variability ranges of body surface maps in a sample of normal subjects. AB - Quantitative data on the normal variability of body surface maps (BSM) are scarce in the literature. This is one of the reasons why BSM are not yet widely used in clinical practice despite their superior information contents. In this study we determined the average value and variability of a number of parameters derived from BSM in a group of 36 normal adult males, ages 22 to 60. Forty to 60 homogeneous beats were averaged for each subject. This enabled us to extend our study to the low voltage intervals (P,PQ,ST,U) which encompass more than 60% of the entire P-U duration and to contribute new data to controversial issues, such as the presence of two simultaneous maxima during atrial excitation. The following parameters were measured: a) the coordinates of the absolute potential maximum and minimum on the chest surface during the entire cardiac cycle; b) the time course of four voltage-related functions, namely: highest instantaneous potential value on the chest surface, lowest (most negative) potential, highest potential difference, and surface integral of the absolute value of the potential function. In recent studies these parameters were shown to be of considerable value in discriminating normal subjects from different categories of cardiac patients. PMID- 3351407 TI - Body surface isopotential maps during the first week of life. AB - One hundred body surface isopotential maps for 30 normal infants, ages three hours to seven days, were evaluated. Ventricular activation and recovery were examined. In the early and mid phase of QRS, the maximum moved from the center of the anterior chest to the lower right portion of the anterior chest. In the late phase, the maximum appeared on the back. The niche appeared earlier in normal newborn infants (19.6 +/- 3.9 msec) (mean +/- S.D.) than in normal children (25.7 +/- 4.6 msec) (P less than 0.001). The location of the maximum at the time of peak positive potentials gradually shifted leftward during the first week of life. The 100 T wave maps were classified into three types. During the first day of life, the T wave maps showed type I or II, changing to type II or III a few days after birth. All T wave maps were type III a week after birth. The ratio of type III gradually increased with age. We found that the QRS maps were different from those of normal children and that T wave maps changed within the first week of birth. PMID- 3351408 TI - Variation in the precordial QRS transition zone in normal subjects. AB - From body surface potential map data for 51 normal young men (with QRS axis between 0 and 90 degrees) both the spatial QRS area vector and the isoarea map of the QRS were obtained. Acting on Grant's assumption that the transition zone defined a plane perpendicular to the spatial QRS vector, we determined the angular shift in altitude and azimuth required to move the spatial vector of each individual to the position of the group mean. We then shifted the precordial map of the transition zone of each individual with the same angular correction. These resulting transition zone boundaries clustered much closer to each other, but did not move into absolute coincidence. We interpreted the nearness-to-fit to be an estimate of the degree to which the precordial QRS configurations conformed to a common simple vector or dipolar pattern. PMID- 3351409 TI - Local conduction delay causes R-wave amplitude increase in patients with effort angina. AB - Eighty-seven unipolar electrocardiograms distributed over the entire thorax were simulataneously recorded before and after treadmill exercise in 43 patients. Exercise-induced R-wave amplitude change (delta R) and peak R time (time from the onset of QRS to the peak of R wave), were calculated for each lead. The maximal delta R of 87 leads was designated as the max delta R. After exercise, regional delay of peak R time (greater than or equal to 10 msec) on the chest was observed in 13 patients. These patients had significantly higher max delta R than those without such regional peak R time delay (0.71 +/- 0.31mV vs. 0.33 +/- 0.20mV, p less than 0.01). In each case, the site of peak R time delay was almost the same as the site of max delta R. There was no significant difference in the peak heart rate, rise of the systolic blood pressure (delta BPs) during exercise or extent of ischemic ST depression between patients with and without peak R time delay. We concluded that ventricular condition delay plays an important role in the increase of R-wave amplitude after exercise in patients with effort angina pectoris. PMID- 3351410 TI - Evaluation of exercise-induced Q-wave amplitude changes and their clinical value. AB - We studied the influence of exercise level, severity of coronary artery disease (CAD), presence of previous myocardial infarction (MI), anterior or diaphragmatic, on the clinical value of exertional Q wave changes (Delta-Q). We retrospectively evaluated the exercise electrocardiograms of 62 patients without angiographic evidence of CAD and 133 patients with CAD; 28 of them had single (SVD) and 105 multivessel disease (MVD). Forty-one patients had a previous diaphragmatic MI and 23 anterior. The sensitivity, specificity and predictive value of Delta-Q were compared to the ST criterion. The exercise level affected Delta-Q. ST and Delta-Q had similar specificity and predictive values. The extent of CAD did not affect the sensitivity of Delta-Q and this method was better than ST to detect SVD patients. The Delta-Q criterion was equally as efficient as ST in MVD patients without MI and with diaphragmatic MI. The loss of septal forces on resting electrocardiograms made useless Delta-Q analysis on patients with anterior MI. The improvement of sensitivity in SVD patients by Delta-Q might be of clinical value since these latter are frequently not diagnosed by the ST criterion. PMID- 3351411 TI - Sensitivity and accuracy in recording His-Purkinje activity by surface-averaged electrocardiography. AB - A clinical evaluation of the surface-averaged ECG (SAE) to record His-Purkinje activity (HPA) was made on 70 patients who underwent His bundle electrograms (HBE). The recorded signals first judged as HPA in 43 patients by the noninvasive method alone were later verified in 37 patients by HBE; the accuracy of the HPA recordings (predictive value) was 86.0%. The HPA-V interval measured noninvasively had a high correlation with the HV interval by HBE (r = 0.89, p less than 0.01). The verified detection rate in all 70 patients was 52.9%: HPA was detected in 12 of 18 patients (66.7%) with sclerotic and hypertensive heart disease (Group I), five of 19 patients (26.3%) with rheumatic heart disease (Group II), 11 of 17 patients (64.7%) with congenital heart disease (Group III), and nine of 16 patients (56.2%) with miscellaneous conditions (Group IV). The detection rate was markedly lower in Group II than in other groups (Group II vs Group I or III, p less than 0.025). The PR segment was significantly longer in the patients in whom HPA was detected than in those in whom it was not detected (71.5 +/- 22.3 msec vs 43.9 +/- 19.5 msec, p less than 0.001). His-Purkinje activity (HPA) was detected in 32 of 52 recordings (61.5%) with sinus rhythm and seven of 20 recordings (35.0%) with atrial fibrillation, including two recordings in each of two cardioverted patients (p less than 0.05). We conclude that the surface-averaged ECG (SAE) has clinically acceptable sensitivity and accuracy except in patients with rheumatic heart disease, short PR segments or atrial fibrillations. PMID- 3351412 TI - Long-standing bidirectional tachycardia in a patient with hypokalemic periodic paralysis. AB - Bidirectional tachycardia is an uncommon arrhythmia that usually occurs in aged persons with severe myocardial disease or digitalis intoxication, and carries a poor prognosis. This is a report of a young woman with familial hypokalemic periodic paralysis, who has a 13-year history of asymptomatic bidirectional tachycardia in the absence of organic heart disease or digitalis intoxication. Association of periodic paralysis and bidirectional tachycardia in this case and four previously reported cases suggests a strong relationship between this arrhythmia and potassium. PMID- 3351413 TI - Intermittent Wolff-Parkinson-White syndrome due to phase 3 and phase 4 block: disappearance of rapid ventricular response during atrial fibrillation. AB - A 65-year-old man with Wolff-Parkinson-White syndrome type A had a rapid ventricular response over an accessory pathway during atrial fibrillation. Four months later, electrophysiological study revealed the following properties: 1) The antegrade accessory pathway conduction showed phase 3 and phase 4 block. 2) The retrograde concealed accessory pathway conduction eliminated phase 4 block in the antegrade accessory pathway conduction. 3) Premature ventricular excitation arose from the accessory pathway or from the ventricular muscle close to its distal end. 4) Atrial fibrillation during isoproterenol infusion did not show rapid ventricular response. Spontaneous impairment of accessory pathway conduction due to phase 3 and phase 4 block was suspected. PMID- 3351415 TI - Selected abstracts. Fourteenth International Congress on Electrocardiology. Berlin, German Democratic Republic, August 17-20, 1987. PMID- 3351414 TI - Verapamil-mediated atrioventricular nodal reentrant tachycardia and the uncovering of dual-pathway AV nodal conduction. AB - In a 67-year-old man with multiple myocardial infarctions in the past, the use of oral verapamil for control of angina pectoris was followed by the appearance of two previously undiagnosed abnormalities, namely, a dual-pathway AV node conduction pattern, and paroxysms of AV nodal reentrant tachycardia precipitated by premature ventricular beats (PVB). It is probable that the differential effects of verapamil on the fast and slow AV node pathways, and the interplay of PVB with its concealment within the AV node, created the necessary circumstances in the AV node to precipitate the tachycardia. Observed off verapamil over several months, the patient remained in normal sinus rhythm but continued to have numerous premature ventricular beats (PVB's). Nevertheless, neither the clinical electrocardiographic features of dual-pathway AV node conduction nor the AV nodal reentrant tachycardia could be found. The proarrhythmic effect of verapamil and its ability to provoke the very arrhythmia against which it is most effective are of particular interest in view of a similar behavior exhibited by the Class I antiarrhythmic agents. PMID- 3351416 TI - The sheep corpus luteum secretes inhibin. AB - An experiment was performed in 20 Merino ewes in which ovarian venous blood was collected by venepuncture at surgery and at two stages of the oestrous cycle. The ovarian venous concentrations of inhibin, oestradiol-17 beta and progesterone were determined. The results demonstrate that during the luteal phase of the oestrous cycle the ovarian venous blood draining an ovary containing luteal tissue contains significantly more inhibin bioactivity than ovarian venous blood from an ovary not containing luteal tissue. During the follicular phase the concentration of inhibin bioactivity in ovarian venous blood was reduced compared with the luteal phase. From this data we conclude that the sheep corpus luteum secretes inhibin bioactivity into the ovarian venous blood. PMID- 3351417 TI - The somatotrophic axis in young steers: influence of nutritional status and oestradiol-17 beta on hepatic high- and low-affinity somatotrophic binding sites. AB - The binding of bovine GH (bGH) to hepatic membranes obtained from steers on either high (3% dry matter of body weight per day) or low (1% dry matter of body weight per day) planes of nutrition with or without an oestradiol-17 beta implant was studied (n = 5 per group). Binding studies were performed on both crude membrane homogenates and on 100,000 g microsomal membrane fractions; identical results were obtained using both preparations. In all four groups of animals, linear Scatchard plots were obtained, but following pretreatment of the membranes with MgCl2 to remove endogenously bound hormone, curvilinear plots were obtained in the groups on the high plane of nutrition. Analysis of these curves suggested the presence of a high- and low-affinity binding site, the high-affinity site being fully occupied in the absence of MgCl2 pretreatment. The specific binding of bGH in MgCl2-pretreated crude membranes was greater (P less than 0.01) in well fed steers (14.8 +/- 1.6%) than in poorly fed steers (9.8 +/- 0.9%). Scatchard analysis showed this to be due to the presence of a high-affinity site (dissociation constant (Kd) = 11.6 +/- 3.3 pmol/l) in the well-fed animals only. In addition, there was an increase (P less than 0.01) in the affinity, but not in the capacity, of the low-affinity site (Kd = 106.4 +/- 22.8 pmol/l in well-fed steers and 197.0 +/- 23.8 pmol/l in poorly fed steers).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351418 TI - A comparison of the vasopressin response of rats to intraperitoneal and intravenous administration of hypertonic saline, and the effect of opioid and aminergic antagonists. AB - The vasopressin response of rats to i.p. injection of hypertonic sodium chloride (1.5 mol/l) was compared with that following i.v. infusion of 1.05 mol sodium chloride/l. The two regimes produced a similar vasopressin response in terms of the osmotic threshold, although the slopes of the plot of plasma vasopressin levels against plasma osmolality were not identical. Pretreatment with naloxone and levallorphan increased the resting vasopressin levels and effectively potentiated vasopressin release in response to hypertonic saline by reducing the osmotic threshold for hormone release. Thus, opioid peptides appear to exert an inhibitory effect on vasopressin release under resting and stimulated conditions. The adrenoreceptor antagonists propranolol, phenyoxybenzamine and phentolamine produced a fall in resting vasopressin concentrations while propranolol and phenoxybenzamine potentiated the osmotic release of vasopressin in association with a fall in the osmotic threshold. This would suggest that noradrenergic pathways are excitatory at rest while having an inhibitory effect on the osmotic response. Metoclopramide also produced a fall in resting plasma vasopressin concentrations while increasing the osmotic response. In contrast haloperidol did not affect the vasopressin response. PMID- 3351419 TI - Reduced oxytocin response to osmotic stimulus and immobilization stress in lactating rats. AB - The release of oxytocin in response to an osmotic stimulus and immobilization stress was compared in lactating rats 8-12 days after delivery and in non lactating rats. Intravenous injection of hypertonic saline or immobilization stress induced an increase in blood oxytocin levels in both lactating and non lactating rats, but the increment in the former was significantly lower than that in the latter. The lower responsiveness of oxytocin release to stress in lactating rats was not altered by ovariectomy 2 days after parturition. Oxytocin release induced by electrical stimulation of the anteroventral third ventricle (an osmoreceptive area), paraventricular nucleus and neurohypophysis was significantly lower, to a similar extent, in lactating rats compared with non lactating rats. These findings indicate that the structural reorganization reported in the hypothalamo-neurohypophysial system may not function to facilitate release of oxytocin in response to stress and osmotic stimulus in lactating rats. The reduced responsiveness of the release of oxytocin is independent of the influence of ovarian hormones, and may be due to the low ability of the oxytocin neurone itself to release oxytocin, and/or due to the activated inhibitory influence on the oxytocin neurone in the lactating rat. PMID- 3351420 TI - The time-course of oxytocin secretion from cultured bovine granulosa cells, stimulated by ascorbate and catecholamines. AB - Bovine granulosa cells secrete oxytocin when cultured in a serum-supplemented medium. The time-course of secretion is similar to that in the early corpus luteum in vivo, with a delay of 1 to 2 days followed by a peak and decline over the first 5 days of culture. We have investigated the basis of this time-course in vitro and studied the temporal characteristics of the stimulatory actions of ascorbic acid and adrenaline on this process. Cells cultured on stirred microcarriers showed a similar pattern of secretion of oxytocin to those cultured on conventional flat plates, despite continuing and rapid mitosis. This indicated that the secretion profile in conventional culture was not an artifact related to the cessation of mitosis. Furthermore, secretion of oxytocin and progesterone by cells on microcarriers was stimulated without a corresponding change in mitotic rate, showing that the secretion per cell had been increased. In conventional culture, addition of ascorbic acid to culture media (0.5 mmol/l) increased the secretion of oxytocin (up to 4.5-fold) but only if ascorbic acid was present during the first day of culture. The cells showed a progressive refractoriness to stimulation after 12 h. Since the time-course of secretion was unaltered by treatment, this resulted in a delay of 1 to 2 days before the action of the ascorbate was seen. The secretion of progesterone was similarly affected but with less stimulation and less consistency. In contrast, cells treated with adrenaline (10 mumol/l) secreted more oxytocin on the day of treatment and did so at any time during culture provided that there was sufficient basal secretion of hormone. Adrenaline also failed to alter the time-course of secretion but treated cells showed a persistent response, maintaining enhanced secretion for up to 3 days after the adrenaline had been removed. Ascorbate and adrenaline were highly synergistic in their effects, provided that the ascorbate was present from the start of culture; the response to adrenaline strongly reflected the degree of ascorbate stimulation. We conclude that granulosa cells secrete oxytocin according to an inherent time-schedule and that there is a limited period during which they can respond to ascorbate. Since ascorbate is required for the biosynthesis of oxytocin, this suggests that the availability of ascorbate during corpus luteum formation may determine the amount of oxytocin which can be released subsequently in response to catecholamines. PMID- 3351421 TI - Vasoactive intestinal peptide and the stimulation of lactotroph growth by oestradiol in rats. AB - Treatment with a high dose of oestradiol for 6 months caused hyperprolactinaemia and pituitary hyperplasia in female Wistar-Furth rats. Changes in the vasoactive intestinal peptide (VIP) and dopamine content of the hypothalamus and pituitary were also found. The hypothalamic dopamine concentration was only slightly reduced and, although the concentration of dopamine in the pituitary was less in treated animals, the total pituitary content was increased. The concentration of VIP in the pituitary was increased by oestradiol treatment but decreased in the non-median eminence hypothalamus. In the median eminence the VIP content was increased by oestradiol treatment and the amount present correlated positively and significantly with pituitary wet weight in animals treated with both oestradiol and fluphenazine. In Fischer 344 rats, oestradiol produced greater incremental changes in pituitary wet weight and plasma concentrations of prolactin than in Wistar controls and the increase in the pituitary concentration of VIP was five times greater. Although peptide turnover has not been measured, these results suggest that oestradiol, as well as having a direct action, stimulates pituitary lactotrophs by increasing pituitary concentrations of VIP. PMID- 3351423 TI - Potentiation of lactation-induced oxytocin secretion by intracerebroventricular oxytocin in the conscious goat. AB - The release of oxytocin into the cerebrospinal fluid (CSF) and plasma of lactating goats was studied following implantation of cisternal and lateral ventricular cannulae. Hand milking was associated with a significant increase in plasma concentrations of oxytocin, but no change in plasma concentrations of vasopressin or CSF concentrations of oxytocin. Intracerebroventricular (i.c.v.) infusion of oxytocin itself (1 pmol/min for 60 min) had no effect on basal plasma levels of oxytocin. It did, however, markedly potentiate the milking-induced increase in plasma oxytocin above the levels achieved during i.c.v. infusion of artificial CSF alone. In the goat, therefore, milking results in a selective release of oxytocin into the plasma, and this release can be potentiated by the presence of increased concentrations of oxytocin in the CSF. PMID- 3351422 TI - Biophysical characteristics of oxytocin secretory granules isolated from ovine corpora lutea. AB - Luteal oxytocin-containing secretory granules have been isolated and characterized in terms of their physicochemical parameters. The isopynic sedimentation density (1.03 +/- 0.003 g/ml) and sedimentation coefficient (1670 S, 0.32 mol sucrose/l, 4 degrees C) of these granules have been estimated. Based upon these estimates, the average vesicle diameter (258 +/- 17 nm) and vesicle weight (9.92 +/- 0.67 fg/vesicle) were calculated. The exchangeable water content (58.2%) of these granules was determined using density gradients prepared with deuterium oxide. Luteal oxytocin-containing granules displayed similar physicochemical characteristics to those reported for neurohypophysial peptide containing granules, with the exception of particle size. Luteal granules were 1.3 times greater in diameter than neurohypophysial granules. PMID- 3351424 TI - Association of progesterone with a unique particulate fraction of the human corpus luteum. AB - Homogenates of human corpus luteum were fractionated on continuous sucrose density gradients, with and without pretreatment with digitonin to perturb plasma membranes. Fractions of each gradient were assayed for steroid content and a range of plasma membrane and intracellular organelle markers. Progesterone and oestradiol were associated with a particulate fraction (buoyant density, 1.08 1.13 g/cm3). The buoyant density distribution of these steroids was distinct from those of the luteal cell plasma membrane and intracellular organelle markers tested. Treatment with digitonin increased the buoyant density of both progesterone and oestradiol. If steroids are contained in distinct vesicles, these vesicles may be involved in the sequestration of newly synthesized steroid and its movement to the cell surface for release into the circulation. PMID- 3351425 TI - Growth hormone is mitogenic for fetal mouse osteoblasts but not for undifferentiated bone cells. AB - More evidence has recently been obtained indicating that growth hormone (GH) has a direct effect on bone. However, it is not clear which cell type reacts to the hormone. The present study used osteoblast-like cells derived from sequentially digested fetal mouse calvaria. Separately cultured tractions resulted in populations enriched in cells with a more or a less differentiated phenotype. The results showed that GH acts on the cells released last, i.e. those with more characteristics of the osteoblast. In these cells, GH induced strong mitogenic activity. Prolactin was not active. PMID- 3351426 TI - A comparative study of endometrial acid phosphatase activity in the mid-luteal phase of the menstrual cycle and in the peri-implantation stage in the rhesus monkey (Macaca mulatta). AB - Acid phosphatase activity in both total and subcellular fractions of endometrium of rhesus monkey on day 5 of gestation was significantly (P less than 0.01) lower than levels found in tissues collected from normally menstruating monkeys on day 5 after ovulation. This endometrial response to preimplantation embryo may be related to the menstrual withdrawal in a fertile cycle. PMID- 3351427 TI - Refractoriness in quail leads to a reduction in the photoperiodic drive on LH secretion. AB - The hypothesis was advanced that the long-day castration response in quail should become less pronounced in birds made refractory by exposure to long photoperiods. This was tested by pretreating two groups of castrated quail with testosterone for 9 weeks to suppress LH secretion whilst exposing them either to short days or to long days. The castration response was then measured on long days by withdrawing the testosterone and following the subsequent rate of increase in LH secretion. In both groups LH concentrations increased steadily for 7 weeks after removing the testosterone but the rate of increase in the group previously exposed to long days was only 50% of that in the group previously held on short days (P less than 0.025). The long-day castration response in quail not pretreated with testosterone was not altered by retaining the birds for 9 weeks on short days before transfer to long days. PMID- 3351428 TI - Modification by pertussis toxin of the responses of bovine anterior pituitary cells to acetylcholine and dopamine: effects on hormone secretion and 86Rb efflux. AB - Acetylcholine is known to stimulate the secretion of growth hormone and prolactin and the efflux of 86Rb from bovine anterior pituitary cells: dopamine prevents the stimulation of 86Rb efflux and of prolactin but not growth hormone secretion. The sensitivity of these responses to pertussis toxin has been determined. Treatment of bovine anterior pituitary cells in primary culture with pertussis toxin (18 h, 100 ng/ml) did not modify the stimulation of prolactin secretion by acetylcholine, but prevented its inhibition by dopamine. In lactotrophs, dopamine but not acetylcholine receptors are therefore coupled to secretion through a pertussis toxin substrate. The stimulation of 86Rb efflux by acetylcholine was also unaffected by pertussis toxin and, again, its inhibition by dopamine was prevented. Treatment of the cells with pertussis toxin enhanced the secretion of growth hormone in response to acetylcholine. Nitrendepine (1 mumol/l) prevented the cholinergic stimulation of growth hormone but not prolactin secretion from these cells. Acetylcholine increased the cytoplasmic calcium concentration and this rise was enhanced by treatment of the cells with pertussis toxin. Nitrendepine partially inhibited the rise in calcium caused by acetylcholine, and prevented the enhancement of the rise following pertussis toxin treatment. Cholinergic stimulation of growth hormone therefore depends on calcium entry through nitrendepine-sensitive channels, whereas stimulation of prolactin secretion does not, and in somatotrophs a pertussis toxin substrate may limit calcium entry through these channels. These different sensitivities of somatotrophs and lactotrophs to pertussis toxin and nitrendepine may reflect differences in the properties of the predominant calcium currents in the two cell types. PMID- 3351429 TI - Endogenous opioid peptide modulation of LH secretion in the ewe lamb: possible involvement of 5-hydroxytryptamine. AB - Evidence from several species suggest that the endogenous opioid peptides participate in the regulation of gonadotrophin and prolactin secretion. The aim of the present study involving intact and ovariectomized prepubertal ewe lambs was to compare the effects in vivo of an opioid peptide agonist [D-Ala2,N Phe4,Met(0)ol5]-enkephalin (FK 33-824) and antagonist, naloxone, on concentrations of LH and prolactin in plasma, and levels of neurotransmitter metabolites in cerebrospinal fluid (CSF), with their effects in vitro on the release of gonadotrophin-releasing hormone (GnRH) and neurotransmitters from isolated median eminences. Infusion of FK 33-824 (0.5 mg/30 min) in vivo depressed plasma LH levels in both intact and ovariectomized lambs; this effect could be reversed by naloxone. In ovariectomized lambs, the inhibitory action of FK 33-824 on plasma LH levels was associated with a 13% rise in the concentration of the metabolite of 5-hydroxytryptamine, 5-hydroxyindolacetic acid (5-HIAA). Concurrent administration of naloxone resulted in an abrupt 33% fall in CSF levels of 5-HIAA. No significant changes in plasma concentrations of prolactin or CSF concentrations of the metabolites of dopamine were observed in response to the administration of FK 33-824 or FK 33-824 plus naloxone. That FK 33-824 inhibited LH release through a central mechanism was confirmed using superfused median eminences in vitro. Thus FK 33-824 (1 mumol/l) greatly diminished the release of GnRH induced by the introduction of a depolarizing stimulus (36 mmol K+/l) in tissue obtained from both intact and ovariectomized ewe lambs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351430 TI - Plasma levels of neuropeptide tyrosine Y (NPY) are increased in human sepsis but are unchanged during canine endotoxin shock despite raised catecholamine concentrations. AB - Alterations in levels of adrenal vein and circulating immunoreactive neuropeptide tyrosine Y (NPY), as well as systemic catecholamine concentrations, have been investigated in the dog after endotoxin administration. Eighteen dogs were anaesthetized with alpha-chloralose and allowed to breathe spontaneously. Severe shock was produced by the administration of a large bolus of Escherichia coli endotoxin followed by a continuous infusion. In two further animals the left lumbar adrenal vein was cannulated and an intermittent choke allowed retrograde sampling of the adrenal effluent. The production of hypodynamic shock was associated with marked increases in systemic catecholamine concentrations but there were no consistent changes in adrenal vein or systemic immunoreactive NPY levels. In contrast, circulating concentrations of immunoreactive NPY were markedly raised above the normal range in five patients with septic shock. PMID- 3351431 TI - Radioimmunoassay of progesterone receptor in human tissues: application to breast cancer. AB - A radioimmunoassay method to measure progesterone receptor in rabbit and human tissues was devised and applied to human breast cancer. A specific progesterone receptor antibody was prepared by purifying rabbit receptor by immunoaffinity chromatography, sodium dodecylsulphate-polyacrylamide gel electrophoresis and injection of the isolated 110,000 dalton receptor band into a goat. Immunoblot studies of progesterone target and non-target tissues showed the specificity of the antibody, which was used at a dilution of 1/45,000. The tracer consisted of 125I-labelled electroeluted 110,000 dalton receptor. The sensitivity of the method was 1 fmol/tube for the rabbit receptor and 3 fmol/tube for the human receptor. The intra-assay coefficient of variation was 11% for tumours positive for the progesterone receptor and 9.9% for those on the borderline (10-30 fmol receptor/mg protein). The interassay coefficients of variation were 20 and 19% respectively. The correlation between the radioimmunoassay and a steroid-binding assay was studied in 40 tumour biopsies. In 39 cases, very good correlation was found (r = 0.99); in a single case an immunoreactive protein was detected which apparently bound steroid poorly. One important feature of this method was that receptor immunoreactivity remained unchanged when either the tissue or the cytosol was exposed to a temperature of 20 degrees C for relatively long periods of time. Under the same conditions the steroid-binding capacity declined rapidly. This characteristic of the radioimmunoassay may prevent errors due to improper handling of tissue samples. Such stability was not observed for oestrogen receptors when measured by a sandwich immunoenzymatic method after incubation of tissue at 20 degrees C. PMID- 3351432 TI - Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism. AB - Parathyroid hormone (PTH) release and cytoplasmic calcium concentrations were investigated at ambient calcium concentrations of 0.5-3.0 mmol/l in dispersed parathyroid cells from 44 hypercalcaemic patients with primary or uraemic hyperparathyroidism (HPT). In comparison with parathyroid cells from adult cattle, release of PTH by human preparations was reduced and values of the ambient calcium concentration causing half-maximal inhibition of PTH release (median effective dose, ED50) were significantly increased. Half-maximal inhibition of PTH release was obtained with concentrations of cytoplasmic calcium almost identical to the concentrations of ionized calcium in the plasma of the individual patients. Cytoplasmic concentrations of calcium in the parathyroid cells were inversely related to release of PTH. Concentrations of cytoplasmic calcium were significantly lower in human than in bovine cells and the ED50 for ambient calcium increase on cytoplasmic calcium was raised to the same extent as the ED50 for ambient calcium inhibition of PTH release in human compared with bovine cells. The magnitude of the increased ED50 for ambient calcium inhibition of PTH release and increase of cytoplasmic calcium concentration was similar in adenomas and sporadic as well as hereditary primary hyperplasias, but the secretion was the least aberrant in uraemic hyperplasias, although they had by far the largest glandular mass. Serum concentrations of total calcium before surgery correlated with the ED50 for ambient calcium effects of PTH release and cytoplasmic calcium, but not with glandular weight. These findings demonstrate a universally abnormal regulation of cytoplasmic calcium in HPT and its importance for PTH release, and that disturbance of cytoplasmic calcium rather than the increased glandular mass contributes to the hypercalcaemia in adenomatous and hyperplastic HPT. PMID- 3351433 TI - A monoclonal antibody (3G5)-defined ganglioside antigen is expressed on the cell surface of microvascular pericytes. AB - The identification of microvascular pericytes in vitro relies principally on morphological characteristics and growth dynamics, as there is a paucity of immunochemical markers for these cells. Consequently, an attempt was made to identify mAb reagents that would aid in both the rapid identification and enrichment of retinal capillary pericytes in vascular cell cultures. A panel of mAbs raised by xenogeneic immunization of mice with various tissues was screened for immunoreactivity with dissociated cultures of bovine retinal capillary pericytes. Two antibodies from the panel (3G5 and HISL-8) were seen to react with pericytes by indirect immunofluorescence. The mAb 3G5 was selected for further study. mAb 3G5 did not react with dissociated cultures of smooth muscle cells, endothelial cells, or retinal pigmented endothelial cells. The pericyte 3G5 antigen was insensitive to the action of trypsin; therefore, mAb 3G5 was used to selectively purify pericytes from trypsinized mixed retinal cell cultures by flow cytometry. 3G5+ pericytes (representing 8% of cells in a mixed retinal cell culture) were enriched at least nine-fold to represent greater than 70% of cells. The mAb 3G5 stained retinal capillaries in vivo with a fluorescence distribution consistent with pericyte staining. The 3G5 antigen of cultured pericytes was found to be a glycolipid of mobility intermediate between ganglioside markers GM1 and GM2. PMID- 3351434 TI - The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. AB - The ability of murine recombinant tumor necrosis factor (rTNF) and natural TNF in tumor-necrotizing serum (TNS) to cause regression of the SA1 sarcoma was investigated. We found that to cause regression of a 9-d SA1 sarcoma, near lethal quantities of rTNF and TNS had to be given to the host. However, even at these highly toxic doses, rTNF was not reliable at causing complete tumor regression. On the other hand, both types of TNF were reliable at causing a tumor hemorrhagic reaction that resulted in the destruction of greater than 75% of the tumor's center in 24 h. The TNF-induced hemorrhagic reaction involved the development of numerous petechial hemorrhages in the tumor's vascular bed, which apparently resulted from destruction of the tumor's blood vessels. It was possible to follow the development of the hemorrhagic reaction against time after giving rTNF or TNS by measuring the intratumor extravasation of 51Cr-labeled syngeneic red cells. According to this method, TNF-induced intratumor hemorrhaging was in progress within 1 h of giving TNF and continued for about a 6-h period. However, the hemorrhagic reaction was greatly reduced and complete regression of the rim of the living tumor tissue that survived hemorrhagic necrosis failed to occur, if SA1 sarcoma was growing in T cell-deficient (TXB) mice. This indicates that the TNF-induced hemorrhagic reaction is partly dependent, and the tumor regression that follows is completely dependent on host immunocompetence. This suggests in turn, that rTNF does not directly destroy SA1 tumor cells in vivo, even though it was shown that it can destroy SA1 tumor cells in vitro. This interpretation is supported by the additional findings that rTNF was no more therapeutic against a 3-d (3-mm) SA1 than against a 9-d (8-mm) SA1, and was no more therapeutic when injected directly into the tumor than when injected intravenously. Lastly it was possible to completely inhibit the ability of rTNF and TNS to cause tumor hemorrhagic necrosis and regression by infusing the host with a monospecific, polyvalent anti-rTNF antibody that neutralized the cytotoxic action of rTNF in vitro. PMID- 3351435 TI - Specificities and V genes encoding monoclonal autoantibodies from viable motheaten mice. AB - Several hundred hybridomas were obtained from 1-2-mo-old viable motheaten (mev) mice. Among the Ig-secreting hybridomas tested, greater than 50% (17/33) exhibited reactivity for autoantigens, supporting the idea that the Ly-1 B cells that predominate in mev mice contain frequent precursors of autoantibody-forming cells. Certain of the specificities of these autoantibodies correlated with the documented pathophysiology of mev mice (antithymocyte, -erythrocyte, -skin, kidney, and -IgG); others were specific for autoantigens not previously observed in motheaten mice but though to be involved in other autoimmune diseases (e.g., intrinsic factor, transferrin, myelin basic protein, and thyroglobulin). About 2 of 3 (11/17) of the self-reactive antibodies exhibited multispecific binding activity for various autoantigens. Analysis by Northern blotting of the V gene families used in mev autoantibodies showed a random usage of VH families and a biased usage of four Vk gene families. Of 16 autoantibodies tested, 12 used a Vk gene from the Vk1, 4, 10, or 19 families. These patterns of Vk gene usage differ from nonautoimmune control animals. Overall, an immunoregulatory defect operating at a more generalized level than the VH or Vk loci, and due to a single gene mutation, appears to be responsible for the multiple immune abnormalities of mev mice. PMID- 3351436 TI - Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. AB - Cachexia is a potentially lethal syndrome of unknown etiology characterized by anorexia, weight loss, and protein wasting that frequently complicates the treatment of chronic inflammation and cancer. Cachectin/TNF was isolated during the search for a humoral mediator of cachexia and found to stimulate the breakdown of energy stores from adipocytes and myocytes in vitro, but the chronic effects of the monokine in vivo are not known. Sublethal doses of recombinant human cachectin administered twice daily for 7-10 d caused cachexia in rats, as evidenced by reduced food intake, weight loss, and depletion of whole-body lipid and protein stores. Significant anemia is also observed and found to be the result of decreased red blood cell mass, not expanded plasma volume. Leukocytosis and histopathological evidence of tissue injury and inflammation are observed in several organs, including omentum, liver, spleen, and heart. These data suggests that the exposure of the normal host to cachectin is capable of inducing a pathophysiological syndrome of cachexia, anemia, and inflammation similar to that observed during inflammatory states or malignancy. PMID- 3351438 TI - Adjusting delay to reinforcement: comparing choice in pigeons and humans. AB - Indifference functions of amount and delay of reinforcement were compared for pigeon and human subjects by using Mazur's (1987) adjusting delay procedure. A model similar to the matching law (the simple reciprocal model), a hyperbolic model, three modified versions of the hyperbolic model, and a negative exponential model were evaluated. In Experiment 1 the subjects were pigeons, and in Experiments 2 and 3 the subjects were humans. In order to make the nonhuman and human situations more comparable, in Experiments 2 and 3 the reinforcer (points exchangeable for money) was discounted at a constant rate during the delay periods. The rate of this discounting varied between Experiments 2 and 3. The results of all three experiments demonstrated that a power function transformation of the hyperbolic model (in which 1 is added to the delays in the denominator of the simple reciprocal model) provided the best description of both nonhuman and human data. PMID- 3351439 TI - Addendum to "Summation in the chimpanzee (Pan troglodytes)". AB - Rumbaugh, Savage-Rumbaugh, and Hegel (1987) reported that two chimpanzees (Pan troglodytes) could select, with better than 90% accuracy, the greater of two paired quantities of chocolate chips. In that study, no one quantity of chocolates (from 0 through 5) was used in both pairs on a given trial. We investigated the effect of having one quantity in common (CQ) in both pairs. Whether the other quantities (OQs) of chocolates were both less than or greater than the CQ, summation still occurred. Accuracy was primarily a function of the ratios of sums to be differentiated. This finding substantiated the earlier conclusion that summation was based on both quantities of each pair and not on some simpler process such as the avoidance of the tray with the smallest single amount or selection of the tray with the single largest amount. PMID- 3351437 TI - Specific localization and imaging of amyloid deposits in vivo using 123I-labeled serum amyloid P component. AB - Highly specific, high-resolution scintigraphic images of amyloid-laden organs in mice with experimentally induced amyloid A protein (AA) amyloidosis were obtained after intravenous injection of 123I-labeled serum amyloid P component (SAP). Interestingly, a much higher proportion (up to 40%) of the injected dose of heterologous human SAP localized to amyloid and was retained there than was the case with isologous mouse SAP, indicating that human SAP binds more avidly to mouse AA fibrils than does mouse SAP. Specificity of SAP localization was established by the failure of the related proteins, human C-reactive protein and Limulus C-reactive protein, to deposit significantly in amyloid and by the absence of human SAP deposition in nonamyloidotic organs. However, only partial correlations were observed between the quantity of SAP localized and two independent estimates, histology and RIA for AA of the amount of amyloid in particular organs. It is not clear which of the three methods used reflects better the extent or clinical significance of the amyloid deposits but in vivo localization of radiolabeled SAP, detectable and quantifiable by gamma camera imaging, is apparently extremely sensitive. These findings establish the use of labeled SAP as a noninvasive in vivo diagnostic probe in experimental amyloidosis, potentially capable of revealing the natural history of the condition, and suggest that it may also be applicable generally as a specific targeting agent for diagnostic and even therapeutic purposes in clinical amyloidosis. PMID- 3351440 TI - Selective attention: effects of cuing on the processing of different types of compound stimuli. AB - Pigeons in a matching-to-sample experiment received (a) element samples (one of two colors or vertical or horizontal white lines), (b) separated compound samples (a color and a line element presented together), and (c) unified compound samples (vertical or horizontal colored lines). In Phase I, test stimuli were the two elements from one dimension; the dimension tested varied randomly when the sample was a compound. Element samples were matched better than unified samples, which were matched better than separated samples. In Phase II, two samples preceded the tests. On EC trials, the first sample (S1) was an element, and the second sample (S2) was a compound; on CE trials this order was reversed. One element of the compound sample was always the one appearing as the element sample on that trial (e.g., S1 = red, S2 = red-vertical). This element also served as the correct test alternative (e.g., test = red+ vs. green) except on probe trials when the correct test was the other element appearing in the compound (e.g., test = vertical+ vs. horizontal). Accuracy varied as a function of sample sequence when the compound was separated (EC greater than CE on nonprobe trials and CE greater than EC on prove trials). This pattern was not observed when the compound was unified. The data suggest that the element in EC trials served as a cue that increased processing of the cued dimension and decreased processing of the noncued dimension of separated compounds. However, both dimensions of unified compounds seem to have been processed regardless of cuing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351441 TI - Neuraminidase induces capacitation and acrosome reaction in mammalian spermatozoa. AB - The treatment of epididymal spermatozoa of guinea pig and ejaculated spermatozoa of rabbit with neuraminidase from Arthrobacter ureafaciens induced significant acrosome reaction while the neuraminidase from Cl. perfringens failed to do so. The addition of the neuraminidase inhibitors kept the enzyme induced acrosome reaction to the control level. The zona-free hamster ova test showed that the treatment of spermatozoa with Arthrobacter neuraminidase rendered 82% of the guinea pig and 69% of the rabbit spermatozoa capable of fertilization. Thus, neuraminidase seems to enhance the rate of acrosome reaction by first capacitating spermatozoa in vitro. PMID- 3351443 TI - Eye regeneration in the mystery snail. AB - Mystery snails (Family Ampullariidae) are aquatic prosobranchs which possess structurally complex eyes at the tip of a cephalic eyestalk. No other sensory organs are found in association with this stalk. These snails possess the ability to regenerate the eye completely after amputation through the mid-eyestalk. Amputation induces gross changes in the cellular character of the entire eyestalk; in particular, an invagination of integumentary epithelium at the apex of the eyestalk stump produces a shallow cleft or "eyecup." Differentiation of all components of the eye apparently occurs by transdetermination of these epithelial cells. Retinal differentiation and the appearance of a new lens is observed as soon as 14 days postamputation. Complete eyes (by external observation), although smaller than the originals, have regenerated by 25 days postamputation. We compare this regeneration to the reconstruction of other animal tissues, in particular the regeneration of amphibian limbs. PMID- 3351442 TI - Effects of colchicine- and cytochalasin B-treatment on the intracellular distribution of yolk droplets, lipid bodies, and Golgi apparatus of the chick neuroepithelial cells. AB - Treatment with colchicine (antimicrotubular agent) and cytochalasin B (antimicrofilamentous agent) has been used to investigate the possible role played by the cytoskeleton in the maintenance of intracellular distribution of yolk droplets, lipid bodies, and Golgi apparatus of the chick neuroepithelial cells. On the one hand, embryos treated with colchicine showed modifications in their distribution patterns of yolk droplets and lipid bodies, which suggests the involvement of the microtubular integrity of neuroepithelial cells in the maintenance of normal distribution patterns. On the other hand, the close relationships between vitelline and lipid inclusions and Golgi apparatus observed in untreated embryos seems to be kept in the embryos treated with colchicine and cytochalasin B. Moreover, from the effects of colchicine on Golgi apparatus position a possible functional role for the microtubular system in the maintenance of Golgi apparatus polarity in the chick neuroepithelial cells can be proposed. The results provided here constitute new information about the cellular mechanisms involved in chick neurulation. PMID- 3351444 TI - Electrical responses to amputation of the eye in the mystery snail. AB - Immediately following amputation through the eyestalk of the mystery snail (Pomacea), a persistent ionic current enters the apical amputation surface of the eyestalk stump. The circuit is completed by current driven from undamaged integument of the eyestalk stump and other body regions. The current is relatively steady during the first 10 hours following amputation. Currents subsequently begin a slow decline to base line levels by 60 hours postamputation- a time coincident with wound healing processes. The "battery" driving this ionic current is the internally negative transepidermal potential existing across the snail integument--perhaps the result of a net inward pumping of chloride across the skin. This system is compared to other regeneration models such as the amphibian limb, bone fracture repair, and skin wound healing. We suggest that ionic current may be a control of eye regeneration in the snail. PMID- 3351445 TI - Differential localization of glycoconjugates having affinity for concanavalin A on the surface of the sperm head in the testis, the epididymis, and the ejaculate of the ram. AB - The localization of Con A receptors on the surface of the head of ram spermatozoa originating from the rete testis, from three regions of the epididymis, or from the ejaculate was investigated using a gold-Con A labelling technique. Electron microscopic observation revealed three major localizations, each being characteristic of the origin of the spermatozoa: periacrosomal in the rete testis, postacrosomal in the epididymis, on the entire surface of the sperm head in the ejaculate. PMID- 3351446 TI - Evidence for the sexual bipotentiality of spermatogonia in the fish, Oryzias latipes. AB - The origin of the oocyte-like cells (testis-ova) induced by the administration of estradiol in the testis of the fish, Oryzias latipes, was examined by light and electron microscopy. A small number of testis-ova at the zygotene stage was seen on the sixth day after the beginning of treatment with estradiol, and on the 12th day testis-ova at the pachytene and diplotene stages were observed. Ultrastructural observations revealed that the testis-ova at the zygotene stage were organized as cysts and that all testis-ova within a given cyst developed synchronously. The number of these testis-ova in each cyst varied but cysts containing 16-20 or 26-30 testis-ova were most frequently observed. Spermatogonia of O. latipes are classified morphologically into two types: the type A and the type B spermatogonia (Grier, '76 Cell Tissue Res., 168:419-431). Type A spermatogonia, which were separated from each other by Sertoli cells, were of the stem type and type B spermatogonia appeared to divide clonally 9-10 times in each cyst before entering meiosis. The present observations on zygotene testis-ova indicate that the testis-ova originate from type B spermatogonia which have divided clonally four or five times, suggesting that male germ cells remain sexually bipotent through the early stages of development of type B spermatogonia. PMID- 3351447 TI - Comparison of heterospermic and homospermic inseminations as measures of male fertility. AB - This study attempted to determine a basis for the previously observed greater sensitivity of heterospermic tests when compared to homospermic tests for detecting differences in fertility between males. In theory, the results of heterospermic tests are an indication of the proportion of eggs fertilized per unit time whereas results of homospermic inseminations measure only the cumulative or final proportion of eggs fertilized. The fertilizing ability of sperm from males of CF1 and C57BL/6N strains of mice was compared homospermically using both relatively high and low concentrations of sperm and by measuring the proportion of eggs penetrated per unit of time. The fertilizing ability of sperm from these strains was also compared using heterospermic inseminations. When females were inseminated with a high concentration of sperm, males of both strains fertilized a high and indistinguishable percentage of eggs when examined after 30 hr. When females were inseminated with either a low concentration of sperm or when the proportion of eggs penetrated was measured at 5 hr, differences between strains of mice were distinguishable. Heterospermic insemination further magnified the observed difference between strains. The results of this study confirm that measuring the percentage of eggs fertilized per unit of time can enhance the magnitude of differences between males in fertility as compared to measuring only the final percentage of eggs fertilized. Measuring the percentage of eggs fertilized per unit of time does not, however, entirely account for the large differences observed between fertility of males when they are compared using heterospermic inseminations. PMID- 3351449 TI - Estimating actual height in the older individual. AB - The widely used formulas for estimating adult stature require modification of the estimated height to account for the effects of age. The recording of measured and reported height in a living older population from southern Arizona, in conjunction with bone mineralization monitoring, provides an opportunity to test the currently used correction factor. Loss of height appears to commence around the age of 45, and the average rate of loss is relatively rapid at 0.16 cm per year. The correction factor suggested by this study is 0.16(age--45), subtracted from the maximum height. The loss is also affected by the maximum height of the individual. In cases of low bone mineralization, the increased incidence of vertebral crush fractures may cause further reductions in standing height. The low rate of recognition of height changes among the older community lowers the usefulness of the age adjusted height estimate. It is recommended that both the maximum and age adjusted heights be provided in forensic science reports to aid in matching with missing person reports. PMID- 3351448 TI - Age related changes in the human plastron: a roentgenographic and morphologic study. AB - Characteristic changes that can be demonstrated on roentgenograms occur with increasing age in the plastron (chest plate) of humans. These alterations include progressive ossification in the costal cartilages (located characteristically in the sternal rib end, centrichondrally, and peristernally--often with sex and age distinctive patterns), maturation of the newly formed bone with trabeculation formation, loss of the smooth contour of the costo-manubrial junction, cupping of rib ends, osteoporotic changes, and arthritic changes in the sternal head of the clavicles. The sequence of development of these alterations has been examined by X-ray of 1965 cadavers of 15 years of age or over and correlated with the gross bone and cartilage morphology changes in many cases. This technique allows for age determination within 5 years of real age in 55% of cadavers and within 25% of real age in 95% of all cadavers. The greatest departures from real age are in the over-60-year groups. The same roentgenograms can allow for correct sex prediction in 99% of the population. PMID- 3351450 TI - Discussion of "Free radical production from controlled low-energy fires: toxicity considerations". PMID- 3351451 TI - Failure of use of cemental annulations in teeth to determine the age of humans. AB - The reliability of cemental annulation counts in teeth was examined to determine its value as an age indicator for humans. One hundred extracted human teeth were embedded in polyester casting resin and sectioned using a diamond wafering saw. Thin sections were photomicrographed, projected, and counted in a double blind random method of presentation. The age of the specimen was determined by adding the number of cemental annulations counted by the observers and the eruption age of the specific tooth that was used. The data analyzed by simple regression indicated that determining chronologic age in humans from cemental annulations is not possible. PMID- 3351453 TI - Duplicating film with an embossed dot. PMID- 3351452 TI - The autodegradation of deoxyribonucleic acid (DNA) in human rib bone and its relationship to the time interval since death. AB - This research explored the feasibility of using the degradation rate of deoxyribonucleic acid (DNA) in human rib bone to determine the time interval since death. Postmortem human rib samples were surface sterilized and incubated under sterile conditions in either high or low humidity conditions at room temperature for a period of weeks. At selected times, portions of the bone were cut away, and the DNA from these samples was extracted and subjected to strand separating gel electrophoresis. The DNAs in the gels were transferred to a nylon membrane, preserving their relative positions as in the gel, and probed with radioactive total genomic human DNA. Autoradiograms produced were scanned and digitized. When the samples were incubated under identical conditions, the degradation rate of DNA in samples from different individuals appeared very similar. The DNA degradation rate may vary with temperature and humidity more than it varies between individuals. PMID- 3351454 TI - Controversial ethical issues in forensic psychiatry: a survey. AB - A survey was conducted of members of the Psychiatry and Behavioral Science section of the American Academy of Forensic Sciences (AAFS) to determine their ethical concerns about controversial items. Issues were included in the survey from the American Psychiatric Association (APA) and AAFS Code of Ethics. Strong support was found for those issues. Some AAPL items from a previous version of their guidelines did not receive support. Fortunately, they have been modified in a later AAPL draft, after AAPL received this survey's results. Clarification was obtained on some ambiguous items from a previous AAFS survey. The present survey showed strong support for addressing in forensic psychiatry's ethical guidelines some issues previously considered too controversial. PMID- 3351455 TI - Discussion of "Effect of hypothermia on breath-alcohol analysis". PMID- 3351456 TI - Discussion of "Reliability of the scoring system of the American Board of Forensic Odontology for Human Bite Marks". PMID- 3351457 TI - Name variation and aspects of body image among male offenders. AB - The author studied 100 incarcerated adult male felons who were referred consecutively for psychiatric evaluation. As part of the investigation, he ascertained whether each man had ever used a name variation, either by self report or as documented in official records. He also administered two body-image questionnaires, each to half of the sample population. Those who used a name variation, however defined, were found to have increased head awareness and decreased stomach awareness when compared with those who had not used a name variation. Otherwise, these groups had no statistically significant differences among a wide group of descriptive variables. The author suggests that the differences in body image may be associated with cognitive differences in the ways in which these subjects approach themselves and their environments. PMID- 3351459 TI - Claims of psychiatric injury after alleged false arrest. AB - Litigation has increased rapidly in the United States; those who feel aggrieved sue readily for damages. Police officers and security people may be sued after arrests or detention followed by unsuccessful prosecution or dropping of criminal charges. Claims of psychiatric injury may be made where there are no discernible damages otherwise. Examiners must keep in mind that physical abuse or grossly inappropriate police behavior may be factors in the ultimate results. This paper reviews 13 cases of claimed psychiatric injury after arrest. Almost all were settled, some for significant amounts. Appropriateness of evaluation, the value of nuisance suits in this type of litigation, the role of attorneys' fees, and the effect of Federal suits as opposed to state suits are discussed. PMID- 3351458 TI - Predicting the effectiveness of treatment for pedophilia. AB - Assessment of progress in a treatment program for pedophiles and the prediction of risk of future offenses are based upon change along four parameters: decreased objective sexual arousal to child stimuli based on negative conditioning and penile tumescence monitoring, decreased emotional congruence with children, improvement in meaningful adult relationships, and effective therapy for disinhibiting factors. The latter three are measured by rating scales completed by both patients and staff. Although statistical analysis of recidivism is in progress, it may not reflect the true frequency of reoffenses. The ability to predict successful treatment is still limited to theoretical and subjective indices. PMID- 3351460 TI - Extractive alkylation and gas chromatographic analysis of sulfide. AB - A sensitive analysis of sulfide in blood was established, using an extractive alkylation technique. Pentafluorobenzyl bromide was used as the alkylating agent, tetradecyldimethylbenzylammonium chloride as the phase-transfer catalyst, and potassium dihydrogenphosphate as the buffer to suppress the formation of sulfide. Mass fragmentography was used to identify the sulfide derivative and gas chromatography with an electron capture detector was used for quantitative determination, with the lowest limit of detection being about 0.01 microgram/g. The blood level of rats exposed to hydrogen sulfide was also determined. PMID- 3351461 TI - Micromethod for MN antigen grouping of dried bloodstains. AB - A micromethod based on the absorption elution technique was shown to be applicable to the detection of M and N blood groups of dried bloodstains on cotton cloth. Each antigen M and N was tested using two different types of antisera. Two hundred different bloodstains, stored up to six months, were analyzed. Conclusive results were obtained for M typing on 2.5-mm-long bloodstained threads. For N typing, some cross-reactivity of homozygous M stains with anti-N sera was observed. This may be explained by the structure of the M and N antigens on the red cell membrane. PMID- 3351462 TI - Identification of human urinary stains by enzyme-linked immunosorbent assay for human uromucoid. AB - An enzyme-linked immunosorbent assay (ELISA) of the sandwich type for identification of human urinary stains using commercially available anti-human uromucoid was developed. When experimentally prepared urinary stains of humans and animals, 2 by 2 cm in area, were subjected to analysis, human stains could be differentiated from animal ones except chimpanzee and Old World monkey ones. Stains of other human body fluids showed negative reactions. The reactions did not decrease when human urinary stains were stored at room temperature for three months. The present ELISA provides a useful presumptive test for urinary stains of human origin. PMID- 3351463 TI - A simple overlay system for data comparison in dental identification. AB - A system for handling dental data in mass disasters and in individual cases is described. The basic method allows for a quick overlay comparison of antemortem and postmortem records. After systematic hole punching in the postmortem form, it can be placed over the antemortem form and nonmatches can be easily detected. Suggested uses in mass disaster and individual cases are discussed, as well as its potential for acquainting rural law enforcement with the value of dental data and its management. PMID- 3351464 TI - Shotcup petal abrasions in close range .410-caliber shotgun injuries. AB - Shotcup petal abrasions centered around a shotgun wound of entrance are generally thought to occur at a range of 30 to 90 cm. A suicidal .410-caliber shotgun injury of the right eye is described in which typical petal abrasions were noted around the entrance wound. However, significant soot deposition around the wound suggested that the range of fire was less than 30 cm and perhaps closer to 15 cm. Test-firing of the weapon and ammunition used by the decedent showed some spread of the shotcup petals at a range of 7.5 cm, progressing to maximum spread at 30 to 52.5 cm. Further testing with other .410 ammunition, containing shotcups, confirmed the spread of shotcup petals at ranges less than 30 cm, irrespective of manufacturer, shotshell length, and birdshot size. When a variety of shotguns were tested, it was found that one weapon with a very short barrel and cylinder bore did not exhibit petal spread until a range of 30 cm was reached. The remaining shotguns, with longer barrels and full choke, all demonstrated definite petal spread at a range of 12.5 cm. The long, narrow configuration of .410 shotcup petals may explain their early spread and the production of petal abrasions at ranges of less than 30 cm. PMID- 3351466 TI - Amitriptyline overdose versus sudden infant death syndrome in a two-month-old white female. PMID- 3351465 TI - Sudden death in a neonate as a result of herpes simplex infection. AB - This paper describes a case of a neonate with disseminated herpes simplex born to a 14-year-old asymptomatic mother. The infant's physical examination was normal at birth, and subsequent abnormalities were so subtle that infection was not recognized during life. Postmortem cultures of liver and spleen grew herpes simplex virus, and immunofluorescent direct antibody typing revealed Type 2. A cervical culture of the mother obtained after the infant's death was negative. PMID- 3351467 TI - Cardiac injury during valve replacement surgery. AB - The commonly referenced mortality of cardiac valve replacement surgery is 2 to 5%. Some of this mortality is due to therapeutic misadventure during the procedure. Therapeutic misadventure during cardiac valve replacement may result in patterned injury of the heart, so that postmortem examination can establish the nature of the surgical injury. A case of patterned myocardial injury during valve replacement surgery is presented, with a review of literature and associated cases. PMID- 3351468 TI - Cranial arteriovenous malformation: suicide by exsanguination. AB - Arteriovenous malformations of the scalp are potential sources of serious bleeding because of their location, inherent weakness, and high flow rates. A 40 year-old man used his vascular lesion as a means of suicide. Selected aspects of the historical background, diagnosis, and treatment of these vascular disorders are described. PMID- 3351469 TI - Terminal ballistic characteristics of Hydra-Shok ammunition: a description of three cases. AB - The Hydra-Shok bullet is characterized by a hollow-point construction, with a distinctive central post in the base of the hollow. These features allow such missiles to be easily identified during the course of an autopsy examination of a gunshot victim. Higher velocity loadings of the Hydra-Shok may fragment along the wound path, occasionally forming a ring-like fragment that suggests this ammunition, but this feature cannot be considered unique. Although radiographic examination is helpful in bullet localization, the characteristic central post may be identified by X-ray only if sufficient expansion results in its exposure. Three cases of shooting deaths involving Hydra-Shok bullets are presented and discussed; in each case, the entrance wounds were indistinguishable from entrances associated with conventional ammunition, and in no instance did the missiles exit from the body (including head, chest, and abdominal wounds). Familiarity with relatively unusual ammunition types such as the Hydra-Shok allows for quick identification by the pathologist at the time of autopsy. PMID- 3351470 TI - Discussion of "Seat belts and human rights: an appraisal". PMID- 3351471 TI - The morphology and evidential significance of human hair roots. AB - A discussion of the morphology of human hair roots is presented. In addition to descriptions of variants of the root appearance for hairs removed from follicles in the three classical growth phases, several other commonly occurring root configurations are described and illustrated with photomicrographs. The possible evidential significance of each in certain case situations is discussed. PMID- 3351472 TI - Discussion of "Pseudoabuse--the misdiagnosis of child abuse". PMID- 3351473 TI - Vaginal fluid zinc concentration as a marker for intercourse. AB - Zinc is present in high concentration in semen, but in low concentration in vaginal fluid. We evaluated vaginal zinc levels as a marker for intercourse by measuring precoital (greater than 11 h after intercourse) or postcoital (less than 5 h after intercourse) zinc and acid phosphatase levels in 26 specimens of vaginal fluid from 18 women. The approximate 95% reference range for zinc in precoital vaginal fluid was 1.2 to 15 micrograms/mL (mean 4.5), and in postcoital vaginal fluid 4.0 to 135 micrograms/mL (mean 24). There is an overlap between the precoital and postcoital reference ranges. Provided that the vaginal fluid zinc level is less than approximately 4.0 micrograms/mL or greater than approximately 15 micrograms/mL, vaginal fluid zinc concentration may be useful as an indicator of intercourse. PMID- 3351474 TI - Sudden death in mitral valve prolapse. AB - Four cases of sudden death in young females with clinical and pathologic features of mitral valve prolapse are discussed. The approach to postmortem examination of the mitral valve is reviewed and various risk factors are stressed. Because of the sudden nature of these deaths, this entity is more commonly seen in medical examiner's populations than hospital autopsies. A practical approach to the investigation of such cases is given. PMID- 3351475 TI - Discussion of "A critical analysis of quantitative fingerprint individuality models". PMID- 3351476 TI - Racial identification from the midfacial skeleton with special reference to American Indians and whites. AB - Successful approaches to race determination of unidentified human remains have been developed by anatomists and physical anthropologists, but few quantitative methods are available for distinguishing American Indian crania from those of whites. The leading method in use today is particularly ineffective in its placement of American Indian skulls from the western regions of the United States. Recent development and testing of a new metric method suggests a much more effective technique. The method involves six breadth and projection measurements of the midfacial skeleton, the calculation of three indices, and a simple direct reading of results. The method has the additional advantage of use in the autopsy room with minimal dissection of soft tissue required. Based upon a less extensive test of East Asian and Arctic Mongoloid crania, the method appears to be even more effective in separating them from the sharp featured whites. Larger samples of American blacks and Polynesians are presently under study and these also appear to separate quite readily from whites using the same or similar sectioning values. PMID- 3351477 TI - Variation in dengue type 2 viruses isolated in Bangkok during 1980. AB - Dengue type-2 viruses isolated in metropolitan Bangkok during 1980 (Bangkok/80) were characterized by oligonucleotide fingerprinting, restriction enzyme (RE) mapping and antigenic analysis using monoclonal antibody probes. Of 10 isolates analysed by oligonucleotide fingerprinting, nine were very closely related, showing 72.5% to 91.4% oligonucleotide homology. One isolate (D80-141) produced a distinctly different fingerprint (55.7% to 58.0% homology) and was less related to other Bangkok/80 dengue-2 virus isolates than to a 1964 Bangkok isolate (16681). RE mapping conducted on complementary dsDNA prepared from three Bangkok/80 isolates, strain 16681 and the prototype New Guinea C strain confirmed that D80-141 was genetically distinct. On antigenic analysis, only one of 22 monoclonal antibody probes produced against representative 1980 Bangkok dengue-2 isolates, D80-100 and D80-141, was able to distinguish between these virus strains. Monoclonal antibody 47-10/10, prepared using D80-100 virus and directed at the NS1 non-structural glycoprotein, had a significantly lower (100-fold) solid phase radioimmune assay endpoint titre for D80-141 antigen than for D80-100 antigen. By the indirect immunofluorescence assay, 47-10/10 had lower antibody endpoint titres against D80-141, the NGC strain and 13 (12%) of 110 Bangkok/80 isolates than to a control antibody preparation. These results suggest that strain D80-141 represents a second minor topotype of dengue-2 which was circulating concurrently with the major endemic topotype in Bangkok in early 1980. PMID- 3351478 TI - Nucleotide sequence of the rubella virus capsid protein gene reveals an unusually high G/C content. AB - The nucleotide sequence of the rubella virus capsid protein (C) gene has been determined from a cDNA clone derived from the 40S genomic RNA. The sequence covers the coding region of the C protein (831 nucleotides), 70 nucleotides of the 5' untranslated region, and the 5' end of the downstream E2 membrane protein gene. The capsid gene is unusually rich in C (41.6%) and G (31.2%) residues (G + C 72.8%), and poor in A (15.4%) and U residues (11.8%). There are regions with long runs of up to 45% C or 35% G residues. The codon usage is non-random, with a strong preference for C and G residues in the third position. Starting from two in-frame AUG codons (seven amino acid residues apart) an open reading frame (ORF) was identified that extended in frame into the ORF coding for the downstream E2 membrane protein gene. Since the amino terminus of the capsid protein is blocked, we could not determine which of the AUGs serve as the initiating codon. To verify that the deduced ORF was correct, we have determined the amino acid sequence of 13 tryptic peptides corresponding to one-third of the C protein. Our data show that the C protein is about 277 residues in length (Mr about 30750). It is very hydrophilic and rich in prolines (14.1%) and arginines (14.4%). Clusters of these amino acids are concentrated in the amino-terminal third of the C protein. No sequence homology to the capsid protein of several alphaviruses was observed. Together with our previous sequence data we have now completed the sequence of the genes coding for the structural proteins C, E2 and E1 of rubella virus. PMID- 3351479 TI - Nucleotide sequence of the fusion and haemagglutinin-neuraminidase glycoprotein genes of Newcastle disease virus, strain Ulster: molecular basis for variations in pathogenicity between strains. AB - The nucleotide sequences of the fusion (F) and haemagglutinin-neuraminidase (HN) glycoprotein genes of the extremely avirulent Newcastle disease virus (NDV) strain Ulster have been determined by sequencing cDNA clones derived from viral genomic RNA. Open reading frames, assumed to encode the F0 and HN0 glycoprotein precursors, were 553 and 616 amino acids long, respectively. Comparisons of the two glycoprotein sequences with those of more virulent NDV strains suggested an explanation for the molecular basis of the wide-ranging differences in virulence observed between strains of NDV. The open reading frame corresponding to the Ulster HN glycoprotein extended beyond the C terminus of more virulent strains. This C-terminal extension was assumed to be responsible for the origin of the HN precursor (HN0) found in strain Ulster and other extremely avirulent strains of NDV. There were fewer basic amino acids at the cleavage site of F0 in strain Ulster than are present in more virulent strains, which may be responsible for the absence of cleavage and activation of F0 from this strain in many host cells. In more virulent strains of NDV, as well as in other paramyxoviruses, a phenylalanine residue occurs at the N terminus of the F1 cleavage fragment. The occurrence of a leucine residue at this position in strain Ulster may be partly responsible for the lack of virulence of this strain. PMID- 3351480 TI - Antiviral, anti-glycoprotein and neutralizing antibodies in foals with equine infectious anaemia virus. AB - Equine infectious anaemia virus is related by genome sequence homology to human immunodeficiency virus, caprine arthritis-encephalitis virus and visna virus. Failure of the host to mount a strong neutralizing response detectable in vitro or to eliminate persistent infection in vivo characterizes lentivirus infections in the natural host. In this study the specificities and neutralizing activity of antibodies induced during experimental infection with equine infectious anaemia virus were investigated using antiviral ELISA, radioimmunoprecipitation and neutralization assays. ELISA antibody titres of 10(5) to 10(6) were demonstrated in samples collected 30 and 60 days after infection. Immunoprecipitation titrations demonstrated that antibody titres to the glycoproteins gp90 and gp45 were 10 to 100 times higher than titres to the internal structural protein, p24. Low levels of neutralizing antibody appeared at 23 to 46 days post-infection. The presence of low levels of neutralizing activity in the presence of high levels of anti-glycoprotein activity suggests that the major immunogenic sites on the viral surface are not sensitive to neutralization. PMID- 3351481 TI - Precursor polypeptides of caprine arthritis-encephalitis lentivirus structural proteins. AB - The synthesis of caprine arthritis-encephalitis virus structural proteins was analysed in infected cells labelled with [35S]methionine and [3H]glucosamine and by translation of virion RNA in vitro. Viral polypeptides were isolated from infected cell lysates or from in vitro translation products by immunoprecipitation with specific antisera and resolved by SDS-PAGE. Results indicated that the gag gene-encoded p28, p19 and p16 virion core proteins were formed by cleavage processing of a 55K Mr precursor with several intermediate polypeptides. The gp135 virion surface glycoprotein, encoded by the env gene, was formed by post-translational modification of a glycosylated precursor of 150K apparent Mr. This precursor was formed by glycosylation of a 90K primary env gene product. PMID- 3351483 TI - Antibodies recognizing human serum albumin are not elicited by immunization with preS2 sequences of the hepatitis B virus envelope protein. AB - Antibodies to the preS2 region of the hepatitis B virus (HBV) envelope protein and to human serum albumin (HSA) were allegedly detected at about the same level in sera of humans with acute or chronic hepatitis B [Hellstrom et al., 1986]. It was claimed that anti-HSA arises as a result of an immune response to the preS2 sequence and that it was involved in hepatocellular damage. Over 100 sera from animals and humans immunized with HBsAg containing preS2 sequences, or with synthetic peptides from the preS1, preS2, and S regions of the HBV env protein were assayed for anti-HSA. The results revealed the following: 1) Immunization with the native preS2 sequence or with unconjugated synthetic peptides derived from that sequence does not result in elicitation of anti-HSA. Therefore the alleged appearance of anti-HSA during hepatitis B cannot be directly related to an anti-preS2-specific immune response. 2) Some synthetic peptides, whether or not they were derived from the preS2 sequence, when linked to certain carriers, but not to others, elicited in rabbits an anti-HSA response, which was markedly lower than the response to the homologous peptide. These anti-HSA antibodies could be separated from anti-preS2-specific antibodies by affinity chromatography and did not recognize the synthetic peptide used for immunization. The use in active immunoprophylaxis of hepatitis B of unconjugated peptides from the preS2 sequence with proven high immunogenicity will avoid carrier/linker-mediated induction of antibodies not relevant to protection against HBV. PMID- 3351482 TI - Presence of antibodies to the polymerase gene product(s) of hepatitis B and woodchuck hepatitis virus in natural and experimental infections. AB - Antibodies against synthetic peptides derived from the polymerase gene of the hepatitis B virus (HBV) were present in 80% of renal dialysis patients infected with HBV and in woodchucks infected with woodchuck hepatitis virus (WHV). Polymerase antibody (anti-pol) appeared as the earliest marker of both HBV and WHV infections in approximately half of the individuals tested, suggesting that these antibodies were generated following early viral replication in the liver during the incubation period and prior to the appearance of virus in the blood. Many HBV- or WHV-infected individuals negative for surface antigen throughout infection also had anti-pol, but anti-pol appeared only after anti-surface, anti core and/or anti-e. The presence of anti-pol did not correlate with other serologic markers of HBV or WHV infection, nor did it correlate with histologically confirmed hepatitis in woodchucks. However, there was a significant correlation between the presence of anti-pol and elevated liver enzyme levels in the sera of renal dialysis patients. In several cases, anti-pol was the sole marker of infection, suggesting that underlying infection and low levels of virus replication were present. Most individuals with anti-pol had antibodies to one of the three synthetic peptides, suggesting it may be immunodominant in natural infections. In human populations, groups with a high frequency of HBV infection have a high frequency of polymerase antibodies, and groups with a low frequency of HBV infection have a low frequency of polymerase antibodies. A standard assay for the detection of polymerase antibodies is described, and possible clinical applications are discussed. PMID- 3351484 TI - Antigenic variation of wild and vaccine rabies strains of Egypt. AB - Nineteen street rabies virus strains, isolated in Egypt from humans (two), dogs (nine), cats (two), farm animals (two), gerbils (three), and a jackal were antigenically analyzed. The Pasteur strain used for the preparation of human rabies vaccine, the Flury high and low egg passage stains (HEP, LEP) used for animal vaccines, and the challenge virus standard (CVS) strain were also assayed. All were examined by the indirect fluorescent antibody test, using a panel of 20 monoclonal antibodies against the nucleocapsid of rabies and rabies-related viruses. The rabies isolates demonstrated patterns of reactivity with the antinucleocapsid panel different from those of the Pasteur, HEP, and CVS strains. Representative human, dog, and rodent isolates were analyzed by neutralization tests in mice, with a second panel of 19 monoclonal antibodies against rabies and Mokola envelope glycoproteins. With this panel, the isolates demonstrated patterns of reactivity different from the vaccine strains. These data indicate antigenic variation between wild virus and vaccine strains. PMID- 3351485 TI - Diagnosis of fetal rubella infection by nucleic acid hybridization. AB - The efficacy of nucleic acid hybridization for the diagnosis of rubella infection in experimental and clinical materials was compared with immunoblot and virus isolation techniques. Our results showed that nucleic acid hybridization is specific and rapid but gives false-negative results when compared with conventional virus isolation in some experimental although not in clinical materials so far examined. For this reason, a failure to demonstrate rubella virus in fetal specimens by this method alone cannot yet be taken as a sole criterion for ruling out fetal rubella infection. PMID- 3351486 TI - Maternal-infant transmission of hepatitis B in Egypt. AB - In order to determine whether maternal-infant (vertical) transmission of hepatitis B is a common route of infection leading to chronic antigenemia in Egypt, 901 asymptomatic women in labor were evaluated. Forty-three women (4.8 percent) were positive for HBsAg, but only one woman was positive for HBeAg. From one year of observation of children born to 13 of the HBsAg-positive mothers, vertical transmission of hepatitis B was estimated to have occurred in approximately 1.7% of births, with chronic antigenemia resulting from 0.6% of births. It was also possible to observe 29 children born to women negative for HBsAg. Horizontal transmission of hepatitis B occurred in 17.2 percent of these children during the first year of life. Maternal-infant transmission of hepatitis B at birth does not appear to be the predominant mechanism of hepatitis B transmission or a common cause of chronic antigenemia in Egypt. The first year after birth appears to be a more important period of hepatitis B transmission. Therefore, vaccination of all children at birth with hepatitis B vaccine could be an effective vaccine strategy despite a low incidence of vertical hepatitis B transmission. PMID- 3351488 TI - Inward and outward irritability in the suicidally inclined. AB - A questionnaire to measure inward irritability and outward irritability was given to college students. Inward irritability scores correlated .27 with outward irritability scores. Those students who had attempted suicide had high inward irritability scores; those who had threatened suicide had high inward and outward irritability scores. Results supported the proposition that some suicidal people may have higher levels of outwardly directed anger than nonsuicidal people. PMID- 3351487 TI - Sequential studies of pre-S2 antigenemia and anti-pre-S2 antibodies in relation to viral replication in acute hepatitis B followed from the early incubation phase. AB - To determine the time sequence of expression of pre-S2 peptide (120-150) during the presymptomatic phase of acute hepatitis B, we used a monoclonal antibody radioimmunoassay in five subjects followed from 30 to 70 days before the onset of liver damage. Pre-S2 peptide was present in serum at low levels from the early incubation phase and started to increase immediately after the first detection of HBV-DNA in serum, in parallel with the increase in HBsAg levels. During the symptomatic phase, levels of pre-S2 peptide declined rapidly; it was no longer detectable after recovery. Anti-pre-S2 antibodies were detected, in four patients, only in the recovery phase. These results demonstrate that expression of pre-S2 peptide occurs very early in the incubation phase of acute HBV infection and is cleared in parallel with HBsAg. Anti-pre-S2 antibodies seem to play no role in viral clearance in these patients. PMID- 3351489 TI - Effects of incidental pictorial and verbal adjuncts on text learning. AB - In this study, college students read and studied texts on historical figures in psychology, which were supplemented by drawings and/or brief biographies of these persons. In Experiment 1, a 2 x 2 between-groups design was conducted in which students received one adjunct with each text, both adjuncts, or neither. In Experiment 2, a single group of students received a within-subjects manipulation of the same adjunct conditions. In the between-groups comparison, students receiving biographies learned less of the target text passages, with the group receiving illustrations and biographies performing least accurately. In the within-subject conditions, texts accompanied by an illustration were better learned, with these students doing best on the text with both picture and biography. The results suggest that adjuncts may emphasize some texts, at the expense of learning from the other texts, but that too much adjunct material interferes with the learning of the target passages. PMID- 3351490 TI - Interaural transfer of aftereffect of changing sound level in a tone. AB - Monaural and interaural aftereffects of unidirectional change of sound level in a tone, were measured by a nulling procedure. The former were always much greater than the latter, demonstrating limited interaural transfer of the aftereffect. This is seen as evidence for a peripheral component in the analysis of changing sound level. Such analysis may contribute to the localization of moving sound sources. An additional, and incidental, finding was that a tone without adaptation elicited a perception of steady loudness when its sound level was diminishing slightly. This is consistent with previous evidence. PMID- 3351492 TI - Lymphangioma of the neck in infants and children. PMID- 3351491 TI - A survey of celiac-sprue patients: effect of dietary restrictions on religious practices. AB - Celiac-Sprue Disease, also referred to as Non-Tropical Sprue, is a dietary disease. Celiac-Sprue patients were asked to complete a questionnaire regarding the effect of dietary restrictions on participation in the Passover meal and reception of Communion. A pilot study suggested that subjects made changes in their religious practices because of dietary restrictions. A second, more detailed survey, was performed in which 58 subjects participated and 14 religions were represented. The results indicated that many subjects made changes in their religious practices (p less than .01), made changes on their own initiative (p less than .01), or violated diet prescribed for the disease under the religious setting versus other settings (p less than .05). PMID- 3351493 TI - Feeding practices of low-income infants: a New Orleans Health Department study. PMID- 3351494 TI - Treatment of impotence: nonsurgical modalities. PMID- 3351495 TI - Evaluation of extravasation during intravenous urography. PMID- 3351496 TI - ECG of the month. Short-cuts. Ventricular preexcitation. PMID- 3351497 TI - Biological psychiatry audited. PMID- 3351498 TI - Schizophrenic symptoms and deterioration. Relation to computed tomographic findings. AB - Thirty-two patients with a research diagnosis of chronic schizophrenia were studied using structured clinical scales for premorbid adjustment, clinical symptomatology, and social deterioration. By computed axial tomography (CAT), ventricle-brain ratio (VBR) and cortical atrophy were assessed. The relation between the clinical variables and CAT findings was assessed using linear correlation. CAT-based subgroups were compared using univariate analysis of variance. Previous findings of ventricular enlargement and cortical atrophy in some schizophrenics were replicated. Premorbid asociality and social deterioration were found to have a modest, positive relation with CAT findings but formal thought disorder had a negative relation to ventricle size. There was no relation between the negative symptoms and CAT measures. Within the CAT positive group the presence of cortical atrophy appeared to be associated with a more severe illness compared with those with ventricular enlargement but the sample sizes were too small to obtain any significant differences. PMID- 3351499 TI - Schizophrenic dementia. Clinical and computed axial tomography correlates. AB - Twenty-seven chronic schizophrenic patients and nine other psychiatric patients closely matched in education were compared on the Halstead-Reitan Battery and the Wechsler Adult Intelligence Scale (WAIS). The schizophrenic patients as a group showed significantly poorer performance on the WAIS (full scale: X +/- SD, 92.9 +/- 2.9 vs. 110.8 +/- 2.1, p less than .002) and the Halstead-Reitan Battery (HRB; Average Impairment Range = 2.1 +/- .2 vs. 1.12 +/- .06, p less than .003). In addition the schizophrenic patients did significantly worse than did nonschizophrenic patients on all WAIS subtests and scored in the impaired range on most HRB subtests. Computed axial tomography scans revealed large ventricles on nine schizophrenic patients and cortical atrophy on three others. Among schizophrenics, the enlarged ventricle group consistently scored the worst. No relationship was seen between neuropsychological test performance and degree of ongoing psychopathology as measured by the Brief Psychiatric Rating Scale. These findings are consistent with previous reports of cognitive impairment in schizophrenia and are discussed in terms of regional localization. They provide additional evidence that the impairment is related to the disease process and that structural abnormalities are associated with the more severe condition. PMID- 3351501 TI - Community treatment environments. Patient vs. staff evaluations. AB - Five New York City partial hospitalization programs serving chronic patients in acute phases of distress were examined. Patient and staff perceptions of their programs were compared and related to their evaluations of the programs. Although both patients and staff reported positive assessments of the help provided by the programs, they had different views regarding which elements or aspects of the programs were most helpful. Patients experienced a greater sense of being helped when the emotional climate of the program was highly evaluated, when the staff had been clear about the program goals and expectations, and when personal problems were not scrutinized. Staff felt that the most important program ingredients were the actual treatment elements dealing with personal and practical problems. The influence of the differing frames of reference of patients and staff are discussed regarding the orientation of community treatment programs for chronic psychiatric patients. PMID- 3351500 TI - The clinical significance of thought disorder across time in psychiatric patients. AB - The occurrence and clinical significance of thought disorder, as measured by general abstraction ability and idiosyncratic abstractions, remains a complex and ambiguous area of inquiry. We studied 49 subjects in a longitudinal design in which the effects of general psychopathology and depression on abstraction function were assessed. Results indicate that a) depressive patients have a generalized abstraction dysfunction not limited to specific content areas, b) some depressive patients have a residual abstraction deficit on discharge from the hospital, c) idiosyncratic abstractions are a characteristic but not pathognomonic marker for schizophrenia, and d) across all subjects, abstraction difficulties represent a seemingly state-dependent "final common pathway" that significantly correlates with general psychopathological impairment rather than level of depression. PMID- 3351502 TI - Bulimia in a pair of monozygotic twins. AB - Bulimia was diagnosed in a pair of monozygotic twins and was manifested in both sisters concurrently through their adolescent years. After a later separation only one continued to manifest the disorder with additional associated features of the bulimic syndrome. The case is presented and suggestions regarding the roles of environmental and genetic factors in the development and course of the disorder are discussed. PMID- 3351503 TI - Neuroleptic malignant syndrome following amoxapine overdose. AB - The case of a patient who developed the neuroleptic malignant syndrome following an overdose of amoxapine is presented. It is suggested that amoxapine, an antidepressant structurally related to the neuroleptic loxapine, be added to the list of medications that can cause this potentially lethal syndrome. This case illustrates the need for careful evaluation and attention to differential diagnosis when psychiatric patients develop physical signs and symptoms. PMID- 3351506 TI - Regeneration studies on a crayfish neuromuscular system. II. Effect of changing the nerve entry point into the muscle field on the gradient of innervation. AB - The superficial flexor muscle of the crayfish is a neuromuscular system in which the neurons form position-dependent connectivity patterns with the muscle fibers. This system could be formed with the help of a single medial-to-lateral gradient during development that embodies positional information. To test this gradient hypothesis we changed the nerve's normal medial entry point into the muscle by transplanting it to the middle of the muscle sheet. When all the muscle fibers were present in the target area, most of the neurons studied passed through a stage during regeneration in which they showed preference for either medial or lateral synapse formation. Those neurons that in normal animals innervated preferentially the medial fibers showed a medial preference for new contacts; the neuron that normally innervated the lateral fibers showed a lateral preference for new contacts; the neuron that normally innervated everywhere regenerated equally well into both medial and lateral fibers. Therefore, these neurons are able to detect information regarding their position within the muscle mass and respond to it by preferential synapse formation. The effect of a positional gradient could not be detected when half of the target field was removed prior to regeneration. In this instance, the neuron that innervated the missing target area now regenerated to almost all the available fibers. It is suggested that the interplay of positional cues with other factors at different points in time could determine the final connectivity patterns formed by these cells. PMID- 3351505 TI - Regeneration studies on a crayfish neuromuscular system. I. Connectivity changes after intersegmental nerve transplants. AB - The superficial flexor muscles of the crayfish are a neuromuscular system of a few muscle cells innervated by six neurons in a precise position-dependent pattern. The neurons are capable of regenerating their normal connectivity patterns within a short span of time when conditions are favorable. The superficial flexor muscles of the second and third segments, despite their similarities in neuronal and muscle cell size and number, have distinctive connectivity patterns; some homologous neurons form similar patterns but other homologous neurons form patterns that are reversed between segments. We transplanted each segment's nerve into each other's muscle in order to observe regeneration of the nerves into a target area that differed in connectivity patterns from their original muscle. During the first weeks of regeneration all neurons formed a connectivity pattern with more connections medially and declining connections laterally, a pattern determined by the medial location of the nerve transplant. This pattern is maintained for most of the neurons, but for some there is an eventual reduction in medial connections as maximum synapse formation shifts to the lateral muscle fibers. Three of the eight neurons studied were able to regenerate connectivity patterns that corresponded to their segment of origin and not to their host muscle. This suggests that intersegmental muscle differences are not influencing the formation of these connectivity patterns, so the neurons will follow their inherent synaptogenesis program. PMID- 3351504 TI - Connections between the nucleus isthmi and the tectum in larval and post metamorphic axolotls. AB - The nucleus isthmi (NI) is the primary relay for the frog's ipsilateral visuotectal projection. Using electrophysiological methods, ipsilateral visuotectal activity has been recorded in thyroxine-treated, postmetamorphic axolotls but not in larval axolotls. In order to determine whether changes in isthmotectal projections are responsible for this change in electrophysiological responsiveness, we have investigated the connections between the tectum and the NI using horseradish peroxidase. Our results indicate that the axolotl's isthmotectal pathways are strikingly similar to those of the frog NI, and that the NI sends bilateral projections to the tecta in both larval and thyroxine treated, postmetamorphic axolotls. Thus, the anatomical connections underlying the ipsilateral visuotectal projection are present during larval stages, despite the lack of electrophysiological evidence for the larval ipsilateral visuotectal projection. We hypothesize that thyroxine-induced metamorphosis produces changes in the terminal arborizations of the crossed isthmotectal projection which allow them to be detected by presynaptic electrophysiological techniques. PMID- 3351507 TI - An identified cell is required for the formation of a major nerve during embryogenesis in the leech. AB - Investigations of the cues by which axonal growth cones navigate long distances to their targets have revealed the use of a rich and complex diversity of cellular and extracellular information. In the present study we describe one of the most conceptually simple pathfinding cues: a single identified cell in the leech, Hirudo medicinalis, that may guide axons several hundred micrometers to innervate a particular target. One of the stereotyped nerves of H. medicinalis is a "sex nerve" that projects from the anterior root of ganglion 6 [SNA (6)] to the male reproductive structures in the adjacent anterior segment. The pathway for SNA (6) is completely underlain by a single peripheral cell, here called the axonal runway cell (ARC), before axons enter the pathway. The ARC is apparently a nonneuronal cell that stains with a monoclonal antibody that recognizes leech muscle cells. The importance of the ARC for establishing SNA(6) was tested by ablating it before axons entered the pathway. When the ARC was killed either by physical disruption with a microelectrode, or by photoablation after filling it with the fluorescent dye Lucifer yellow, SNA(6) always failed to form, whereas all other nerves formed normally. Killing other peripheral cells in proximity to the ARC did not interfere with SNA(6) formation. Ablation of possible "pioneer neurons" for SNA(6) also did not prevent its formation. These results show that formation of a particular nerve requires only a single cell to serve as a guide for outgrowing processes. PMID- 3351508 TI - Acetylcholine receptor clustering and triton solubility: neural effect. AB - Previous studies by Prives et al. (1980, 1982a and b) have shown that acetylcholine receptors (AchRs) are extracted from muscle cells in vitro by Triton X-100 at different rates, and that clustered receptors extract most slowly. The present study was aimed at comparing the relative extractability of receptors in clusters with those in intercluster regions and the role of neural factors in regulating this extractability. Using primary rat muscle cells in vitro we confirmed that receptor extraction with Triton X-100 does not fit a single exponential but has more than one rate, and that in control cells clustered receptors extract more slowly than do receptors in intercluster regions. The major new observation in this study was that neural extract lowered the overall Triton extraction rate of intercluster receptors to that of clustered receptors. Additional new observations include the findings that (1) both clustered and intercluster receptors show multiphasic extraction rates; (2) stabilization of AchRs against Triton extraction increases with time in the surface membrane; (3) the effect of neural extract on Triton extractability of AChR is dependent on factors that control RNA synthesis, cytoskeletal elements, and collagen; (4) fixation and/or buffer washes accelerate receptor extraction only in cells that are treated with Triton, but not in control cells; (5) in control cells (not exposed to neural factors) Triton X-100 causes new clusters to form. From experiments using Con A we suggest that the Triton-induced new clusters may not be formed by a redistribution of receptors but are, most likely, due to the presence of groups of intercluster receptors with extraction rates lower than those of surrounding receptors. PMID- 3351509 TI - Recovery of cognitive function soon after stroke: a study of visual neglect, attention span and verbal recall. AB - Sixty two consecutive patients admitted to hospital and surviving 6 months were tested regularly over the first 3 months after their stroke to plot recovery in three aspects of cognition: visual neglect, assessed using a cancellation task, attention span assessed using digit span, and verbal recall, tested by counting number of words remembered from a list of 10 words. Normative data were collected for the cancellation test. Fifteen patients showed recovery from visual neglect, 10 improvement in attention span and nine improvement in verbal recall. The difficulties of measuring recovery of cognitive function after stroke are discussed. PMID- 3351511 TI - Cerebral infarction does not occur typically at night. AB - In a hospital-based series of 66 consecutive patients with non-progressive cerebral infarction, the time of onset and the type of infarction on computed tomography were studied retrospectively. Forty-six (78%) patients suffered cerebral infarction between 6 am and 6 pm. Only five patients (8%) had their infarct between midnight and 6 am. Only three patients had a watershed-infarct, and these occurred during the daytime. Our results do not support the belief that atherothrombotic brain infarction is largely determined by haemodynamic factors. PMID- 3351510 TI - Outcome of shunt operation on urinary incontinence in normal pressure hydrocephalus predicted by lumbar puncture. AB - Bladder function in four patients with normal pressure hydrocephalus, one with dementia of Alzheimer type and five patients with multi-infarct dementia was studied by history and urodynamic tests (cystometry and Bor's ice water test). The bladder hyperactivity could be temporarily improved by a lumbar puncture and removal of 50 ml CSF and later abolished by a shunt operation in patients with normal pressure hydrocephalus while no changes occurred in the other patients. Urodynamic testing in connection with a lumbar puncture may be a reliable way to predict the outcome of a shunt operation in cases of normal pressure hydrocephalus. PMID- 3351512 TI - Brain shrinkage in alcoholics is not caused by changes in hydration: a pathological study. AB - Measurement of the water content of the cerebral white matter in 26 control and 24 alcoholic cases supports in vivo MRI studies and previous necropsy studies which appeared to show an increase in the water content in the alcoholic group. This negates the hypothesis that reversible brain shrinkage in alcoholics is caused by changes in the state of hydration. PMID- 3351514 TI - Learning and forgetting during posttraumatic amnesia in head injured patients. AB - To investigate forgetting during recovery from head injury, colour slides were initially projected for long durations to ensure acquisition on a recognition test given 10 minutes later. Patients tested during posttraumatic amnesia (PTA) exhibited accelerated forgetting over 32 hours as compared with head trauma patients studied after the period of PTA and normal controls. PMID- 3351513 TI - The rigid spine syndrome in two sisters. AB - Two half-sisters aged 14 and 18 years are described with a rigid spine syndrome as the cardinal clinical feature of an autosomal dominant neuromuscular disorder. Ten years previously, a diagnosis of multicore disease had been made from the clinical signs and muscle biopsy findings. Long term follow-up revealed a non specific muscular dystrophy with axial predominance and a rigid spine in the younger girl; the older sister presented at the age of 18 with a rigid spine as the only myopathic sign. Computed tomography of the muscles showed severe involvement of the paraspinal musculature, in contrast with either less or no involvement of the other muscles. PMID- 3351515 TI - Intermittent pyramidal claudication as presenting and sole symptom in multiple sclerosis. PMID- 3351516 TI - Unexplained chronic subarachnoid bleeding and a slowly progressive neurological syndrome. PMID- 3351517 TI - Complete gaze palsy in pontine haemorrhage. PMID- 3351518 TI - Late onset posthemiplegic dystonia in systemic lupus erythematosus. PMID- 3351519 TI - Asymptomatic cardiac arrhythmias in periodic paralysis. PMID- 3351520 TI - Kluver-Bucy syndrome associated with delayed post-anoxic leucoencephalopathy following carbon monoxide poisoning. PMID- 3351521 TI - Local autonomic failure affecting a limb. PMID- 3351522 TI - Local autonomic failure affecting one limb. PMID- 3351523 TI - Schistosoma in the spinal cord. PMID- 3351525 TI - Chronic relapsing inflammatory polyneuropathy complicating sicca syndrome. PMID- 3351524 TI - Aggravation of Parkinson's disease by cinnarizine. PMID- 3351526 TI - Thymoma without myasthenia gravis: electrophysiological study after thymectomy. PMID- 3351527 TI - Stridor during dystonia phases of Parkinson's disease. PMID- 3351528 TI - Quantitative objective assessment of peripheral nociceptive C fibre function. AB - A technique is described for the quantitative assessment of peripheral nociceptive C fibre function by measurement of the axon reflex flare. Acetylcholine, introduced by electrophoresis, is used to stimulate a ring of nociceptive C fibre endings at the centre of which the increase in blood flow is measured with a laser Doppler flowmeter. This flare (neurogenic vasodilatation) has been compared with mechanically or chemically stimulated non-neurogenic cutaneous vasodilation. The flare is abolished by local anaesthetic and is absent in denervated skin. The flare has been measured on the sole of the foot of 96 healthy subjects; its size decreases with age in males, but not in females. PMID- 3351529 TI - Sensory and pain threshold characteristics to laser stimuli. AB - The clinical applications of thermal sensory and pain thresholds have been very limited due to large intra-individual variations. In the present paper CO2 and argon lasers were used as thermal stimulators, and the different factors (stimulus parameters and skin conditions) affecting the thresholds are described. The intra-individual variations obtained in sensory (9.3%) and pain (4.3%) thresholds were very low, which suggests that the method can be applied for clinical purposes. PMID- 3351530 TI - Argon laser induced single cortical responses: a new method to quantify pre-pain and pain perceptions. AB - The shape (amplitude and latency) of single cortical responses to argon laser stimulation was found to match six perceptual classes: three pre-pain and three pain. The amplitude of the pain related single cortical responses correlated with the perceived feeling of pain. Easy detectable responses were obtained because habituation to the stimuli was reduced and a high degree of attention was given to each stimulus. Single cortical responses to argon laser stimuli are suggested as a new quantitative technique with application in the assessment of function in the thermal and nociceptive pathways. PMID- 3351531 TI - Evaluation of proximal facial nerve conduction by transcranial magnetic stimulation. AB - A magnetic stimulator was used for direct transcutaneous stimulation of the intracranial portion of the facial nerve in 15 normal subjects and in patients with Bell's palsy, demyelinating neuropathy, traumatic facial palsy and pontine glioma. Compound muscle action potentials (CMAPs) thus elicited in the orbicularis oris muscle of controls were of similar amplitude but longer latency (1.3 SD 0.15 ms) compared with CMAPs produced by conventional electrical stimulation at the stylomastoid foramen. No response to magnetic stimulation could be recorded from the affected side in 15 of 16 patients with Bell's palsy. Serial studies in two patients demonstrated that the facial nerve remained inexcitable by magnetic stimulation despite marked improvement in clinical function. In the patient with a pontine glioma, the CMAP elicited by transcranial magnetic stimulation was of low amplitude but normal latency. In six of seven patients with demyelinating neuropathy, the response to intracranial magnetic stimulation was significantly delayed. Magnetic stimulation produced no response in either patient with traumatic facial palsy. Although the precise site of facial nerve stimulation is uncertain, evidence points to the labyrinthine segment of the facial canal as the most likely location. PMID- 3351532 TI - Lumbosacral plexus lesions: correlation of clinical signs and computed tomography. AB - Neurological signs and computed tomographic morphology were compared in 60 patients. The primary neurological deficit was most commonly located in the sacral (n = 31) or lumbar plexus (n = 23) and was most commonly caused by a neoplasm (n = 40). In 78% of the patients it correlated with the lesions detected by computed tomography (CT). CT reliably demonstrates extraspinal mass lesions, but only moderately well predicts functional signs. PMID- 3351535 TI - Variation of radon levels in U.S. homes with various forms. PMID- 3351533 TI - Eosinophilic meningitis and radiculomyelitis in Thailand, caused by CNS invasion of Gnathostoma spinigerum and Angiostrongylus cantonensis. AB - During the 6 year period from January 1980 to December 1985 44 patients with infection of the central nervous system by Gnathostoma spinigerum or Angiostrongylus cantonensis were admitted to the Division of Neurology, Ramathibodi Hospital, Bangkok, Thailand. In 16 patients the diagnosis could be confirmed serologically by means of ELISA techniques. In gnathostomiasis encephalitis, myelitis, radiculitis and subarachnoid haemorrhage formed the majority of clinical syndromes. Intracerebral haematoma and transitory obstructive hydrocephalus are described in this report as being caused by Gnathostoma spinigerum infection for the first time. In angiostronglyus infections the clinical syndrome of meningitis was predominant, but one patient, whose angiostrongyliasis was proved serologically, also showed bilateral paresis of abducens nerve. The main laboratory finding was eosinophilic pleocytosis in the CSF (greater than 10%) which in patients originating or returning from South East-Asia, particularly Thailand, is highly suggestive of these parasitic infections. Increasing transcontinental travel, influx of refugees and those seeking asylum as well as importation of food from South East Asian countries demand greater awareness of these parasitic infections even in Central Europe. PMID- 3351534 TI - Effects of hypotension induced with sodium nitroprusside on the cerebral circulation before, and one week after, the subarachnoid injection of blood. AB - Cerebral blood flow (CBF) and mean arterial pressure (MAP) were monitored in six normal baboons and six further animals in which an artificial subarachnoid haemorrhage (SAH) had been induced one week previously. MAP was reduced by the infusion of sodium nitroprusside. In the normal animals with administration of sodium nitroprusside, CBF increased initially but started to decrease as MAP was reduced below 65 mm Hg and fell below its baseline value when MAP was less than 50 mm Hg. In the SAH group, there was no initial hyperaemic response and CBF fell below baseline values when MAP was reduced below 50 mm Hg. When, during the infusion of the sodium nitroprusside, MAP was returned to normal using angiotensin, CBF increased above its baseline value. These results suggest that the cerebrovascular effects of sodium nitroprusside are the net result of competition between direct cerebral vasodilatation, falling arterial blood pressure and the degree of impairment of the "autoregulatory" mechanism. Evidence of ischaemic brain damage was found in the arterial boundary zones of both groups of animals. PMID- 3351536 TI - Air pollution and morbidity: a further analysis of the Los Angeles student nurses data. PMID- 3351537 TI - Hazardous waste minimization: Part I. Waste reduction in the chemical industry. Du Pont's approach. PMID- 3351538 TI - Managing low-volume wastes. From fossil fuel fired power plants. PMID- 3351539 TI - A scale for the estimation of sleep problems in clinical research. AB - Problems in sleeping are widely prevalent in modern society and are often one of the presenting complaints of patients consulting physicians. In addition, there is scattered epidemiologic evidence and considerable clinical support that disturbed or inadequate sleep may be a risk factor for clinical emergence of cardiovascular disease and for total mortality. The role of sleep problems both as a precursor and as a sequela of disease states could be better delineated in large groups by the availability of a brief, reliable and standardized scale for sleep disturbance. Such a scale could also be used to evaluate the impact of different therapies upon sleep problems. This paper presents data from two study populations responding to three and four item self-report scales. From 9 to 12% of air traffic controllers reported various sleep problems to have occurred on half or more of the days during the prior month, whereas 12-22% of patients 6 months after cardiac surgery reported such frequent sleep problems. Utilizing data from the 6 and 12 month follow-ups, test-retest reliability of the three item scale in cardiac surgery patients was found to be 0.59. Internal consistency coefficients for the three and four-item scales were 0.63 and 0.79 respectively. PMID- 3351540 TI - Preliminary observations on maternal rating of health of children: data from three subspecialty clinics. AB - Although routinely used in health surveys, the factors affecting maternal perceptions of health in children, especially those with health problems, have received little examination. This question has been addressed using a telephone interview of families of 483 children followed in one of three clinics at Children's Hospital of Philadelphia: the Neonatal Follow-up Program, the Pediatric Rheumatology Center and the Spina Bifida Program. Limitations in activities of daily living due to the health of the child, medical care use and variables indicative of socio-economic disadvantage were associated with a maternal rating of child health as fair/poor in all groups. The relationship was strongest in the rheumatologic group and less strong in the other two, suggesting that mothers may distinguish between a chronic active disease in a previously healthy child and the disability following a neonatal event in conceptualizing health. The results add to our information about maternal perceptions in assessing child health and suggest ways in which such ratings may prove useful in assessing health and health services for children with health problems. PMID- 3351541 TI - A method of quantify confounding in regression analyses applied to data on diet and CHD incidence. AB - We present a method to display the results of linear regression when the independent variables are highly correlated. In this method the sum of squares of regression (SSR) for pairs of variables are partitioned into orthogonal and shared components. A shared component is the reduction in the SSR of one of the variables when the other variable is added to the regression equation. This method shows how the SSR for one variable depends on the other variables present in the regression equation and explains apparent inconsistencies between forward and backward stepwise regression. To demonstrate the potential usefulness of this method we reanalyzed previously reported data on the relationship between coronary heart disease (CHD) and diet. The analysis suggested that carbohydrate and alcohol intake are negatively associated with CHD because they are associated with greater caloric intake. Protein and fat intake are also associated with greater caloric intake, but in addition they are associated with factors that increase the risk of CHD. PMID- 3351542 TI - Mortality from liver cirrhosis in Italy: proportion associated with consumption of alcohol. AB - A descriptive analysis of the features of mortality from cirrhosis in Italy suggests that it is made up of two components which are characterized by different age trends. On the basis of this hypothesis, a model has been postulated and applied to the data for the 94 Italian provinces in order to identify the two components. When considering alcoholic drinking data, it appears that only one of these components is associated with the consumption of alcohol, both for men and for women. In this way an estimate can be made of the proportion of mortality in Italy which can be linked to alcohol consumption. For males, this is 40.4% (47.1% for the North, 29.7% for Central Italy, and 33% for the South/Islands). For females, the average is 24.6% (36.6% for the North, 16.2% for Central Italy, and 12.3% for the South/Islands). In absolute terms, these figures represent approx 5000 of the 13,000 deaths per year among males and around 1200 of the 5000 deaths from cirrhosis among females. PMID- 3351543 TI - Evaluation of univariate ranges with a multivariate standard. AB - In medical decision making generally many test results are produced. Several authors have discussed the problems involved and concluded that a multivariate approach often has to be preferred. Because until now such an approach has not often been used in practice and qualitative arguments for a multivariate approach are seldom supported by quantitative results, in this paper the use of univariate reference ranges is evaluated with a multivariate range as the standard, taking into account correlation coefficients. Probabilities of false positive and false negative results and predictive values are computed and displayed for decision rules based on two separate test results with an elliptic region as the gold standard. The conclusion is that the quality of the univariate approach is dependent on the correlation coefficient and on the choice of the decision rule. In the most important cases, however, it falls short compared with a multivariate approach. For example, the probability that a univariate positive result is false is around 50% for all values of the correlation coefficient, which is unacceptably high. PMID- 3351544 TI - Period and cohort trends for mortality and cigarette consumption in England and Wales, 1946 to 1980, with emphasis on sex ratios. AB - In an earlier paper (Burch P. R. J. J Chron Dis 1981; 34: 87-103) changes in sex- and age-specific mortality from all causes of death in England and Wales were studied in relation to changes in sex- and age-specific cigarette consumption. The absence of a consistent correlation between the two variables, and the general characteristics of the data, suggested that studies of sex ratios might provide a better test of the hypothesis that the association between smoking and mortality has a causal basis. In this paper temporal changes in the sex ratio of cumulative cigarette consumption by cohort, and of smoking rates by age, are considered in relation to changes in the sex ratio of mortality. Again, no consistent correlations emerge and it is evident that factors other than smoking have played a dominant part in determining recent changes in the sex ratio of mortality in all age groups from 35-39 to 80-84 years. Among these "other factors" are birth cohort effects that can be attributed, in part, to birth cohort changes in the sex ratio of mortality from bronchitis and emphysema. The present results, together with other evidence (vide supra; and Burch P. R. J. J Chron Dis 1984; 37: 148-156), show that great care needs to be exercised when attempts are made to deduce causation from epidemiologic surveys. PMID- 3351545 TI - Adult physical activity behavior: a trend analysis. AB - One of the health objectives for the nation is to have 60% of adults 18-64 years regularly active in vigorous physical activity by 1990. In this paper an effort is made to determine whether American society is making satisfactory progress toward this goal. Two independent databases are analyzed: time diaries collected from a national sample of American adults in 1981; and the Simmons Market Research Bureau, Inc., survey undertaken in 1984. Participation of adults 25-64 in moderate to vigorous activities that included racquet sports, swimming, hiking, bicycling, skiing, jogging, outdoor gardening, skating, etc. is compared between the two time periods. After adjusting for social desirability bias the results indicated there were a similar number of non-participants of the activities analyzed in 1981 and 1984. There was, however, an increase in the number of adults participating occasionally in vigorous activity, although, there did not appear to be any increase in the number who were regularly active, i.e. at least 3 days/week. Thus, while there are indications that adults 25-64 years are adopting more vigorous activity, less than 20% were regular enough in 1984 for improvements in cardiovascular functioning to occur. Unless there were dramatic increases in the activity status of adults 18-24 years of age which was not assessed in this study, the 1990 goal is unlikely to be met. PMID- 3351547 TI - Public health nursing documentation and case management through the use of flowsheets. PMID- 3351546 TI - A comparison of physician and patient reports of Pap smear histories. AB - We describe the level of agreement between patients and their physicians with respect to their use of the Pap smear, the symptoms present, and the smear results. The data derived from a case-control interview study of 181 newly diagnosed invasive squamous cell cervical cancer cases and 905 age-matched controls, a second case-control interview study of 250 cases of cervical dysplasia and 500 age-matched controls, and the medical records of attending physicians for all patients. Cases and controls in both studies reported more smears over the previous 5 years than their medical records indicated; also patients reported their last smear as more recent than noted in physician files. Cancer cases were somewhat more accurate on frequency and timing of smears than the other patient groups. Patients tend to report more symptoms at interview than recorded in their files. Disagreements on smear results were probably because of differences in terminology, especially in distinguishing invasive from pre cancerous conditions; cancer cases tended to report some dysplasias as cancer, but the controls in both studies under-reported dysplasia. If high physician response rates can be obtained, we would prefer to use physician records as the basis of evaluation of screening programs, especially when accurate dating of screening events is required. However it is less clear whether physician records are to be preferred, if the evaluation is to take symptoms into account. PMID- 3351548 TI - Differences in physical health, social interaction, and personal adjustment between continent and incontinent homebound aged women. PMID- 3351549 TI - An analysis of nurse recording in family health clinics of a county health department. PMID- 3351550 TI - Reducing infant mortality: assessing a regional effort. PMID- 3351551 TI - Prevention of AIDS in blacks and Hispanics: nursing implications. PMID- 3351552 TI - Social risk factors: impact on elders' perceived health status. PMID- 3351553 TI - Ventricular assist devices: applications for critical care. PMID- 3351554 TI - Effects of nursing interventions on cardiac output in the patient with a total artificial heart. PMID- 3351555 TI - Nursing considerations in the administration of verapamil. PMID- 3351556 TI - Muscle-powered cardiac assist: a new alternative on the horizon. PMID- 3351557 TI - Identifying a researchable problem. PMID- 3351558 TI - Infusions, age, and drug dosages: learning about large-cell lymphoma. PMID- 3351560 TI - Malignant pleural mesothelioma: a disease unaffected by current therapeutic maneuvers. AB - From 1965 to 1985, 262 patients with malignant pleural mesothelioma were treated with cytostatics only; radiotherapy (RT); RT and cytostatics; or decortication plus RT plus cytostatics. The median survival (MS) from diagnosis was 9.6 months. This was similar for all comparable treatment groups. In a univariate analysis, significant favorable prognostic factors were good performance status (PS), duration of symptoms greater than 6 months at the time of diagnosis, early stage of disease, white race, and female sex. In a multivariate analysis, PS, race, duration of symptoms, and stage were of significance for a favorable prognosis. Age, pain as first symptom, histologic subtype, and RT dose were not of prognosis significance in this study. The stepwise addition of treatment modalities did not increase survival, which remained the same as that reported for untreated patients. Therefore, phase II trials of new agents offer the only hope for advance in the treatment of this disease. PMID- 3351559 TI - Combined radiotherapy and chemotherapy in stage T3 and T4 nasopharyngeal carcinoma in children. AB - Twelve children younger than 16 years affected by undifferentiated nasopharyngeal carcinoma (NPC) with advanced primary tumor (T3, T4) were treated with chemotherapy consisting of Adriamycin (ADM [doxorubicin; Adria Laboratories, Columbus, OH]), vincristine (VCR), and cyclophosphamide (CYC), and radiotherapy. Preradiation chemotherapy produced partial responses in eight of ten evaluable patients. Eleven of 12 patients achieved a complete response following radiotherapy. The actuarial 3-year continuous relapse-free survival (CRFS) was 75%. This represents a significant improvement when compared with the 8% rate obtained in a previous series of patients treated with radiotherapy either with or without adjuvant CYC. PMID- 3351561 TI - Acute leukemia and pregnancy. PMID- 3351562 TI - Rethinking medical oncology training and education. PMID- 3351563 TI - Vertical vestibuloocular reflex in cat: asymmetry and adaptation. AB - 1. We studied eye velocity during the first 2 s of the vertical vestibuloocular reflex (VOR) elicited from cats placed on their sides (90 degrees roll position) and rotated about an earth vertical axis. Vestibular stimuli were presented in the dark and consisted of brief trapezoidal velocity profiles. Eye movements were recorded with a magnetic search coil, and eye velocity was analyzed with high temporal resolution. 2. The first 2 s of upward or downward eye velocity after the onset of head rotation was characterized and compared. Adaptive changes in VOR gain (eye/head velocity) were then induced, and upward and downward eye velocity responses were again compared. 3. The early time course of the vertical VOR was complex. After a latency of approximately 15 ms, eye velocity increased rapidly until it was equal in magnitude and opposite in direction to head velocity. The peak eye velocity decayed within less than 1 s to a plateau of slow phase eye velocity (SPEV) equal to approximately -0.6 times the head velocity. Peak upward and downward eye velocity was symmetric. The transition from peak to plateau was more rapid for the downward VOR (slow phases downward) than for the upward VOR (slow phases upward). The plateau attained by upward SPEV was approximately 15% higher than the plateau attained by downward SPEV. 4. VOR gain adaptation was symmetric. The percentage change in adapted upward eye velocity equalled the percentage change in adapted downward eye velocity. Both peak and plateau SPEV adapted, but peak eye velocity adapted less than plateau eye velocity. VOR latency was unchanged by adaptation. 5. The trajectory of the VOR response to steps of head velocity could be divided into an invariant and a variant interval. The invariant interval consisted of the initial approximately 15 ms of the eye movement. Neither direction of head movement (upward vs. downward) nor adaptation of the VOR gain effected the eye movement trajectory during the invariant interval. The variant interval began approximately 30 ms after the onset of head movement and approximately 15 ms after the onset of eye movement. In unadapted animals, downward eye speed exceeded upward eye speed during the variant interval. In adapted animals, eye speed during the variant interval, but not during the invariant interval, diverged from eye speed in the unadapted state. We suggest that the initial invariant interval (approximately 15 ms) of the eye movement response trajectory may represent the direct response of the classically described three-neuron arc.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351565 TI - Response variability of X- and Y-cells in the dorsal lateral geniculate nucleus of the cat. AB - 1. We measured the variability of neural responses in the dorsal lateral geniculate nucleus (dLGN) of the anesthetized, paralyzed cat during repeated visual stimulation with sinusoidal grating patterns. Results are reported for 11 X-cells and 16 Y-cells recorded in laminae A and A1. 2. The responses of most X- and Y-cells varied markedly from trial to trial. The standard deviations of prestimulus, base-line discharge rate. In contrast, the standard deviations of poststimulus responses increased only slightly or not at all with increases in mean discharge rate. 3. Standard deviations of poststimulus responses to optimal stimuli were about one-third the size of mean discharge rates. Relative variability (standard deviation/mean) increased markedly and in nonlinear fashion with decreases in response amplitude, which resulted in considerable overlap of base-line and poststimulus response distributions when stimuli were less than optimal. PMID- 3351564 TI - Single-unit analysis of the human ventral thalamic nuclear group: somatosensory responses. AB - 1. We have studied the functional and somatotopic properties of 531 single mechanoreceptive thalamic neurons in humans undergoing stereotactic surgery for the control of movement disorders and pain. The majority of these somatosensory cells had small receptive fields (RFs) and were activated in a reproducible manner by mechanical stimuli applied to the skin or deep tissues. These neurons, which we termed "lemniscal," could be further classified into those responding to stimulation of cutaneous (76% of lemniscal sensory cells) or deep (24%) structures. 2. The incidence of neurons having cutaneous or mucosal RFs in the perioral region, thumb, and fingers (66%) was much higher than that of neurons having RFs elsewhere on the body. Most of the deep cells were activated by movements of and/or mechanical stimuli delivered to muscles or tendons controlling the elbow, wrist, and fingers. 3. Sequences of cells spanning several millimeters in the parasagittal plane often exhibited overlapping RFs. However, RFs changed markedly for cells separated by the same distances in the mediolateral direction. This suggests that the cutaneous somatotopic representation of each region of the body is organized into relatively thin sheets of cells oriented in the parasagittal plane. 4. By comparing neuronal RFs in different parasagittal planes in thalamus of individual patients we have identified a mediolateral representation of body surface following the sequence from: intraoral structures, face, thumb through fifth finger to palm, with forearm and leg laterally. 5. Along many trajectories in the parasagittal plane the sequence of cells with overlapping RFs was interrupted by another sequence of cells with RFs corresponding to a different body region. The RFs of the intervening sequence characteristically represented body regions known to be located more medially in thalamus (see 3 above). These findings could be explained if the lamellae postulated above were laterally convex. 6. Cells responding to deep stimulation (deep cells) could be further classified into those responding to joint movement (63%), deep pressure (15%), or both (22%). Deep cells were found usually at the anterior-dorsal border and sometimes at the posterior border of the region containing cells responding to cutaneous stimuli. Although there was some overlap in the RFs, deep cells representing wrist were found medial to those representing elbow, and both of these were found medial to cells representing leg.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351566 TI - Acute inflammation of the knee joint in the cat alters responses of flexor motoneurons to leg movements. AB - 1. This is a report of changes in reflex excitability of flexor motoneurons in response to innocuous mechanical stimuli following initiation of an acute experimental inflammation of the knee joint in the chloralose-anaesthetized cat spinalized at level T12. 2. Activity of functionally single alpha- or gamma- motoneurons, identified by ventral root stimulation, was recorded in filaments of the nerve to biceps semitendinosus before and after onset of an acute inflammation. The inflammation was evoked by injection into the knee cavity of the compounds kaolin and carrageenan. 3. Measurements were made of resting activity, responses to local pressure applied to parts of the upper or lower limb, and to flexion or extension movements at the knee joint before and after onset of the inflammation. In two experiments, one in which no inflammation was initiated, and another in which recordings were made only after the inflammation had fully developed, a survey of large numbers of neurons (44 alpha and 84 gamma) showed that under control conditions only 14% of alpha-motoneurons showed a response to mechanical stimulation compared with 41% of gamma-motoneurons. In the presence of an inflammation 41% of alpha-cells were responsive compared with 64% of gamma-cells. 4. Inflammation-induced changes in activity of motoneurons including both excitatory and inhibitory effects, took 1-2 h to fully develop. Excitatory effects included a rise in resting discharge, an increase in the response to local pressure, and an increased response to flexion and/or to extension of the knee. Inhibitory effects included falls in resting discharge and/or in the responses to leg movements. 5. For 35 cells identified as alpha motoneurons and tested both before and after initiation of an inflammation, 20 remained unresponsive throughout the experiment, whereas 4 that had not responded during the control period began after inflammation to respond to local pressure and/or flexion/extension movements. Of 11 units that exhibited some response before inflammation, 8 showed an increase with inflammation, whereas 2 became unresponsive. 6. The inflammation had rather more dramatic effects on gamma neurons. Many showed control responses to leg movements, and these were measurably modified by inflammation. Of 56 gamma-cells tested under control conditions, 26 were unresponsive to all stimuli, whereas 30 showed some form of response including activity during flexion and extension movements of the leg. Where responses were tested both before and after onset of an inflammation, 11 of 13 unresponsive units remained unresponsive.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351567 TI - Activity during mastication of periodontal mechanosensitive neurons of the trigeminal subnucleus oralis of the rabbit. AB - 1. The activity of mechanosensitive neurons was examined before and during mastication. One hundred and seventy-eight neurons were recorded in the rostral parts of the trigeminal sensory nuclei of 20 rabbits anesthetized with urethan. Twenty-eight neurons received inputs from the periodontal mechanoreceptors, all on the ipsilateral side. Nineteen had receptive fields that were restricted to one tooth; 2 could be activated from more than 1 tooth, and 6 included parts of the mucosa. Only the latter were spontaneously active. 2. All periodontal neurons with a mandibular input responded to graded electrical stimulation of the inferior alveolar nerve at minimum latencies of less than or equal to 3.4 ms, and approximately half had inputs from the sensorimotor cortex. 3. Almost all periodontal units recorded were found to lie in, or just outside, the dorsal part of the most rostral subdivision of the spinal trigeminal nucleus (subnucleus oralis, pars gamma). None projected to the ipsi- or contralateral thalamus. 4. All periodontal neurons fired during mastication. Those without mucosal receptive fields fired during jaw closure, with almost all activity confined to the slow closing phase when pressure is applied to the teeth. Injections of local anesthetic showed that input from mucosal fields was responsible for activating neurons in other phases of the cycle. 5. Possible roles in the control of mastication for these periodontal interneurons were discussed. PMID- 3351568 TI - Electrophysiological characteristics of hamster dorsal root ganglion cells and their response to axotomy. AB - 1. The active and passive membrane properties of neurons in the lower lumbar (L6, L7) or sacral (S1) dorsal root ganglia from golden hamsters were examined in vitro by means of conventional intracellular recording techniques. Data were collected from neurons exhibiting action potentials (AP) of 70 mV or more in amplitude. 2. Cells with axonal conduction velocities (CV) greater than 20 m/s were termed fast-A-cells, those with CVs between 2.5 and 20 m/s were termed A delta-cells, and those with CVs less than 1 m/s were termed C-cells. 3. Fast-A cells usually exhibited short-duration APs (2.51 +/- 0.41 ms, n = 19) followed by short (less than 50 ms) afterhyperpolarizations (AHPs). C-cells usually exhibited long-duration APs (10.5 +/- 0.69 ms, n = 18) followed by long-duration AHPs (much greater than 50 ms). The characteristics of APs in A-delta-cells (AP mean duration 3.34 +/- 0.42 ms, n = 32) were intermediate between those of fast-A- and C-cells. Long AHPs (duration much greater than 50 ms) were manifest in 43.8% of A delta-cells. 4. A time-dependent sag in hyperpolarizing electrotonic potentials (rectification) was found in 68.8% of fast-A-cells, 45.5% of A-delta-cells, and 62.5% of C-cells. 5. To examine neuronal properties 1-6 wk after transection of the sciatic nerve (axotomy), cells were reclassified as SAP (short action potential) cells and LAP (long action potential) cells. Cells in the SAP category had AP durations less than 5 ms and included all fast-A-cells and the majority of A-delta-cells. The LAP category included cells with AP durations greater than 8 ms contained only C-cells. 6. Axotomy failed to decrease the CV of LAP cells or A delta-cells in the SAP group. The CV of LAP cells may have increased (P less than 0.05), whereas that of SAP cells was unchanged. 7. The duration of the AP and AHP of SAP cells were slightly increased (0.1 greater than P greater than 0.05), whereas AP and AHP duration of LAP cells were unchanged after axotomy. AHP amplitudes of all cell types tended to be smaller (0.1 greater than P greater than 0.05). Axotomy did not alter the resting membrane potential or reduce the incidence of rectification in any cell type. 8. Invasion of the soma by axonally evoked APs was impeded in all cell types after axotomy even though a decrease (P less than 0.05) in rheobase of SAP cells occurred.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351570 TI - Slow conductances in neurons from cat sensorimotor cortex in vitro and their role in slow excitability changes. AB - 1. The electrophysiological and pharmacological properties of slow afterpotentials in large layer V neurons from cat sensorimotor cortex were studied in an in vitro slice preparation using intracellular recording and single microelectrode voltage clamp. These properties were used to assess the role of afterpotential mechanisms in prolonged excitability changes. 2. The mean duration of a slow afterhyperpolarization (sAHP) was 13.5 s following 100 spikes evoked at 100 Hz. Its time course was best described by two exponential components, which decayed with time constants of several hundred milliseconds (the early sAHP) and several seconds (the late sAHP). The amplitude of both the early and late components were sensitive to membrane potential and raised extracellular K+ concentration [( K+]o). 3. The early sAHP was reduced when divalent cations were substituted for Ca2+, whereas the late sAHP was unaffected. We conclude that a Ca2+-mediated K+ conductance is responsible for much of the early sAHP. In the presence of tetrodotoxin (TTX), 1-s voltage-clamp steps were used to evoke slow AHPs or outward ionic currents. These AHPs and currents were abolished in Ca2+ free perfusate, but they had a maximum duration of only a few seconds. Thus the slowest outward currents we could observe during voltage clamp in TTX were responsible only for the early sAHP. 4. The possible role of an electrogenic Na+ K+ pump in the late sAHP was examined by applying ouabain to the slice. Ouabain did not reduce selectively the late sAHP, and its effect was best explained by a decrease in intracellular K+ concentration and an increase in [K+]o. 5. Muscarinic and beta-adrenergic agonists reduced or abolished the entire (early and late) sAHP. Neither type of agonist affected the Ca2+-dependent, apamin sensitive medium-duration afterhyperpolarization (35). We conclude that both the Ca2+-mediated K+ conductance underlying the early sAHP and the Ca2+-independent mechanisms underlying the late sAHP are sensitive to at least two classes of transmitter agonists. 6. We focused on the muscarinic effects. When concentrations greater than 5 microM were employed, the entire (early and late) sAHP was replaced by a slow afterdepolarization (sADP). Muscarine reduced the sAHP directly by reducing the underlying outward ionic currents and indirectly by causing the sADP. The sADP was Ca2+-mediated, since it was abolished by Ca2+-free perfusate but not by TTX. 7. The ionic currents underlying the sAHP and the sADP influenced excitability for seconds following evoked repetitive firing.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351569 TI - Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro. AB - 1. Potassium conductances were studied in large layer V neurons using an in vitro slice preparation of cat sensorimotor cortex. The kinetics and pharmacological sensitivity of K+ currents were studied directly using single microelectrode voltage clamp and indirectly by evoking single or multiple spikes and recording the spike repolarization and subsequent afterhyperpolarizations (AHPs). 2. A fast decaying afterhyperpolarization (fAHP) and a subsequent medium-duration afterhyperpolarization (mAHP) followed a single spike. The amplitude and duration of the mAHP increased when multiple spikes were evoked at a fast rate (e.g., 100 Hz), and a slower afterhyperpolarization (sAHP) appeared only after sustained repetitive firing. 3. All AHPs were reduced by membrane potential hyperpolarization and raised extracellular K+ concentration, suggesting they were caused by an increased K+ conductance. Only the mAHP and sAHP reversed at the estimated value of potassium equilibrium potential (-100 mV), whereas the mean reversal potential of the fAHP was nearly identical to the mean value of resting potential (-71 mV). 4. Mechanisms underlying spike repolarization, the fAHP, and the mAHP were investigated. Two rapidly activating outward currents, a fast inactivating current and a slowly inactivating delayed rectifier, were detected by voltage clamp. Both currents were reduced rapidly by tetraethylammonium (TEA). The fast transient current was reduced slowly after divalent cations were substituted for Ca2+ (through a mechanism unrelated to blockade of Ca2+ channels), whereas the delayed rectifier was unaffected. 5. Spike duration was increased and the fAHP was abolished only by blocking agents that reduced the fast outward currents. Effects of extracellular and intracellular TEA were similar. Effects of TEA and Ca2+-free perfusate were additive and resembled the effects of intracellular Cs+. The addition of apamin, d-tubocurare, or Cd2+ was ineffective. We conclude that the two fast outward currents reflect pharmacologically and kinetically separate K+ conductances that are primarily responsible for spike repolarization and the fAHP. 6. Voltage-clamp studies revealed two additional outward currents, which were persistent and Ca2+ mediated. Each current activated and deactivated slowly, but the kinetics of one component were approximately 10 times slower than the other. The decay of these currents gave rise to AHPs resembling the mAHP and the early sAHP. 7. Neither the mAHP nor the sAHP was reduced by TEA. The mAHP was reduced when divalent cations were substituted for Ca2+ or when Cd2+, apamin, or d-tubocurare were added.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351572 TI - The axon terminal of goldfish retinal horizontal cells: a low membrane conductance measured in solitary preparations and its implication to the signal conduction from the soma. AB - 1. Mechanical dissociation of the enzyme-treated goldfish retina yielded somata and axon terminals of horizontal cells. The membrane properties of these solitary axon terminals were investigated using the whole-cell patch-clamp technique. 2. Axon terminals had a large input resistance, comparable to the seal resistance (approximately 30 G omega). Most axon terminals (greater than 80%) showed a nearly linear current-voltage relation between -60 and +10 mV, where the slope conductance was as small as 5 muS/cm2. Some axon terminals showed a shallow negative slope conductance in the same potential range. 3. The membrane current consisted of two components: transient and sustained. The transient component was carried by sodium ions, and the sustained component was a mixture of calcium and potassium currents. The sodium current (INa) was activated by depolarization of beyond -45 mV and was maximal (approximately 60 pA) at -10 mV. It was blocked by 5 microM tetrodotoxin and disappeared in Na+-free medium. The maximum amplitude of INa was less than 10% of INa of the soma. 4. A small calcium current (less than 6 pA) was isolated in a small proportion of cells, with an amplitude approximately 5% of the calcium current evoked in the soma under the identical recording conditions. 5. A small amount of potassium current through the anomalous rectifier was induced in the axon terminal when the membrane potential was below -60 mV. Its conductance was 15-20 muS/cm2, only 1/20 of the estimate in the soma. Other types of potassium currents were not detected. 6. It is concluded that the soma and the axon terminal have a similar set of membrane currents, but the specific membrane conductance of the axon terminal is extremely low. The signal conductivity from soma to axon terminal was assessed using a passive cable model together with numerical values obtained from the present experiments. Although the membrane conductance of the connecting axon was not measurable directly, the calculation strongly suggests that low conductance of the axon terminal membrane minimizes the leakage of signals arriving electrotonically through the thin connecting axon, even if the membrane conductance of the axon was overestimated as being identical to the soma membrane. 7. These results can explain why light-evoked responses recorded from the axon terminal are similar in amplitude as well as in waveform to those recorded from the soma, despite the lack of direct inputs from photoreceptors. PMID- 3351571 TI - Influence of anomalous rectifier activation on afterhyperpolarizations of neurons from cat sensorimotor cortex in vitro. AB - 1. Large neurons from layer V of cat sensorimotor cortex (Betz cells) were studied to determine the influence of the anomalous rectifier current (IAR) on slow afterhyperpolarizations (AHPs). The neurons were examined using intracellular recording and single-microelectrode voltage clamp in an in vitro brain slice preparation. 2. A faster medium-duration AHP (mAHP) and slower AHP (sAHP) followed repetitive firing (22, 23). The amplitude of the mAHP often increased or remained constant during membrane potential hyperpolarization. The membrane potential trajectory resulting solely from IAR activation was similar to the mAHP. 3. Postrepetitive firing voltage clamp was used to measure directly slowly decaying K+ currents (IK) and IAR at different membrane potentials. IK exhibited both a fast and slow decay. The time constants of the fast decay of IK and IAR activation were similar. IAR increased with hyperpolarization or raised extracellular K+ concentration [( K+]o), whereas both the fast and slow components of IK reversed or nulled near -100 mV and behaved as pure K+ currents in response to raised [K+]o. 4. To determine the precise contribution of IK and IAR to the AHP waveform, theoretical AHPs were computed using a quantitative model based on voltage-clamp measurements. The calculated AHPs were qualitatively similar to measured AHPs. The amplitude of the mAHP showed little change with hyperpolarization because of the increasing dominance of IAR at more negative membrane potentials. The sAHP was little affected by IAR activation. 5. Several model parameters subject to biological variation among Betz cells were varied in the calculations to determine their importance in the AHP waveform. With IK parameters held constant, the amplitude and time course of the mAHP depended on resting potential, membrane time constant, the kinetics of the anomalous rectifier conductance (GAR), and the maximum value of GAR. IAR activation could result in a biphasic AHP even when the fast decay of IK was omitted from the calculations. 6. A wider variation of model parameters revealed behavior that may be relevant to other neurons. Certain values of membrane or IAR activation time constants resulted in a monophasic AHP even when the fast decay of IK was present. The decay of a biphasic AHP could reflect either the onset of IAR or the fast decay of IK, depending on the relative value of their time constants. Procedures are outlined to discriminate between these possibilities using current clamp methods.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351573 TI - Gastric mill activity in the lobster. I. Spontaneous modes of chewing. AB - 1. The gastric central pattern generator (CPG) driving the three teeth of the gastric mill inside the lobster stomach has often been used as a model for the study of central nervous systems, but the actual functioning of the mill has never been observed directly. By using a small endoscope inserted through the esophagus a video analysis of the tooth movements was performed with restrained, but otherwise intact lobsters. 2. The teeth show spontaneous periodic chewing (cycle duration from 4 to 70 s) in two different basic modes. In the squeeze mode only the cusps of the three teeth move together simultaneously. In the cut-and grind mode the lateral teeth close first with not only their cusps, but also their serrated edges. After this cut phase the lateral teeth grind backward along the file of the medial tooth, which simultaneously moves forward. 3. Simultaneous endoscope recordings of the teeth, filming of stomach muscles and ossicles combined with electrical stimulation of selected muscles reveal that muscle gm3c is responsible for this hitherto unknown backward grinding of the lateral teeth. 4. The complete behavioral repertoire includes the following modifications of the two basic modes. 1) The lateral teeth can perform chewing movements while the medial tooth stays still and vice versa, forms of chewing regarded even weaker than the squeeze. 2) There do not appear to be intermediates between the squeeze and cut-and-grind movements, with the latter as the strongest form of chewing. Transitions only occur as switching on a cycle-by-cycle basis. 3) A gradual change of the cut-and-grind chewing was observed as the gradual development of an additional opening over the time course of several periods. 4) After their grind phase, the lateral teeth can even move further back beyond the medial tooth. This can serve to push food into the pyloric filter apparatus. 5. Inflation of the cardiac sac can elicit single bites in a resting gastric mill. 6. The behavioral repertoire is compared with the in vivo activity of the gastric oscillator represented by simultaneous intracellular recording from 7 representative cells of the 11 CPG neurons. PMID- 3351574 TI - Gastric mill activity in the lobster. III. Effects of proctolin on the isolated central pattern generator. AB - 1. The response of the isolated gastric central pattern generator (CPG) to bath application of proctolin is characterized and compared with the previously analyzed behavioral response. 2. Proctolin had an excitatory effect on the ongoing spontaneous rhythm of "combined" preparations, in which the stomatogastric ganglion (STG) is connected to the esophageal and commissural ganglia by the stomatogastric nerve (STN). The effect started between 20 s and 5 min and was characterized by strongly increased burst durations as well as increased spike rates in all units except the two lateral posterior gastric (LPG) motoneurons. The effect was strongest in the dorsal gastric (DG) and lateral gastric (LG) motoneurons and was accompanied by a phase change of the DG burst. DG continued spiking throughout large parts of the burst of LG and of the gastric mill (GM) motoneurons, which are antagonists of DG. 3. The threshold concentration was approximately 10(-10) M, and the effects were dose dependent and reversible. 4. LG and DG were identified as target cells for the action of proctolin. In LG regenerative plateau properties were induced, as revealed by its long-lasting plateau potentials, sensitivity for triggering inputs, and the occurrence of oscillatory prepotentials. An induction of endogenous bursting in DG was concluded from preparations, in which DG was cycling alone or bursting with a much shorter period duration than other gastric neurons. Hyperpolarization of DG, which normally has no or weak driving power within the gastric network, demonstrated that under the influence of proctolin, firing of DG can accelerate the gastric rhythm from a 27- to a 9-s period duration. 5. Proctolin does not only have a modulatory influence on an ongoing rhythm, but it also can trigger gastric activity. This function was first concluded from proctolin-treated STGs, which, unlike normal preparations, continue bursting if inputs via the STN are blocked. Finally, triggering was demonstrated directly, since isolated STGs that were not oscillating started a gastric rhythm after 20-30 min of perfusion with proctolin. 6. The proctolin-induced changes of the CPG activity in isolated preparations are in agreement with the effect on gastric mill chewing in the intact animal, in which, depending on the dose, different modes of chewing could be elicited. PMID- 3351575 TI - Influence of auditory localization cues on neuronal activity in the auditory thalamus of the cat. AB - 1. The response properties of auditory thalamic neurons to the two major localization cues characterizing the azimuth of sound sources in the horizontal plane were investigated in cats. Single-unit responses to auditory stimuli (white noise and tones) presented with interaural phase differences (IPD) or interaural intensity differences (IID) were studied. 2. The proportion of neurons in the medial geniculate body that were sensitive to the localization cues tested was 28% for IPD (n = 253) and 37% for IID (n = 65). Half of the IID-sensitive units were also sensitive to IPD, but when the range of IPDs and IIDs to which each unit responded was converted to the sound-source locations that would generate those ranges they did not always correspond to overlapping azimuth angles. 3. The changes in discharge rate in response to the two localization cues occurred over very broad IPD and IID ranges. If this activity is involved in the representation of acoustic space, then the responses of individual neurons do not provide fine spatial tuning. 4. Contralateral and ipsilateral ear leads were represented in a continuous manner by the maximum discharge rate of IPD-sensitive units. On the other hand, units that were sensitive to IIDs were activated over one of two delimited ranges of IIDs. The first corresponded to IID combinations in which the stimulus was presented at a higher intensity in one ear than in the other (for 15/17 units the contralateral one); these were the lateralized intensity response field units. The second are the centered intensity response field units, whose responses were maximal when the intensity was equal in both ears and decreased when IIDs were introduced. PMID- 3351576 TI - Neural mechanisms in vibrotactile adaptation. AB - 1. Peripheral and central neural contributions to vibrotactile adaptation were investigated in decerebrate or anesthetized cats by recording from sensory nerve fibers associated with Pacinian corpuscle (PC) receptors and from central neurons of the dorsal column nuclei that receive their input from vibration-sensitive receptors of the forelimb footpads. Responsiveness of units was assessed using 1 s duration, test vibration stimuli delivered with 1- to 2-mm-diam probes at different times following adapting trains of vibration (usually 300 Hz) that lasted from less than 1 min up to 50 min. 2. Cuneate neuron responsiveness underwent marked depression following prior vibration. The extent of the depression and the time course of recovery in responsiveness were dependent on the intensity and duration of the adapting vibratory stimulus. The recovery time course (often several minutes) was approximately exponential and resembled the reported time course of subjective vibrotactile adaptation obtained in psychophysical experiments. 3. Response depression in PC fibers was only seen at low amplitudes of the test vibration and displayed a brief time course of recovery in comparison with that seen in cuneate neurons. It is therefore unlikely to account for the adaptation time course either in cuneate neurons or at a subjective level. Furthermore, as the adaptation seen in PC fiber responses had a similar time course in both cutaneous and mesenteric PC fibers it is unlikely that mechanical changes in the skin contribute significantly to the adaptation in PC fiber responses to vibration. 4. The time course of afferent induced inhibition following long periods of prior vibration was too brief to account for the response adaptation in cuneate neurons. 5. As the long-term response depression in cuneate neurons following their prior activation was seen for inputs from unconditioned sites within the neuron's excitatory receptive field, as well as from the conditioned site, it appears that the response adaptation is attributable to changes in the central neuron or in synaptic processes associated with the central neuron. It is proposed that this adaptation may be due to an increase in extracellular potassium ion concentration that alters the responsiveness of the central neurons. PMID- 3351577 TI - Delay-tuned combination-sensitive neurons in the auditory cortex of the vocalizing mustached bat. AB - 1. FM-FM neurons in the auditory cortex of the mustached bat are sensitive to a pair of frequency-modulated (FM) sounds that simulates an FM component of the orientation sound and an FM component of the echo. These neurons are tuned to particular delays between the two FM components, suggesting an encoding of target range information. The response properties of these FM-FM neurons, however, have previously been studied only with synthesized orientation sounds and echoes delivered from a loud-speaker as substitutes for the bat's own orientation sounds and corresponding echoes. In this study, the combination sensitivity and delay tuning of FM-FM neurons were examined while the bat was actively vocalizing. 2. When the bat produced orientation sounds in an anechoic environment, or synthesized single FM echoes were delivered to a silent bat, the FM-FM neurons showed weak or no response. In contrast, when synthesized FM echoes were delivered with a particular delay from the FM component of the vocalized orientation sounds, the FM-FM neurons exhibited strong facilitative responses. 3. In both the vocalizing bats and the silent bats with substituted synthesized orientation sounds, all FM-FM neurons tested responded preferentially to the same echo harmonic (FM2, FM3, or FM4). 4. In vocalizing bats, FM-FM neurons showed maximum response to an echo FM component delivered with a particular delay (best delay) from an FM component in the orientation sound. Best delays measured with vocalized orientation sounds were nearly the same as those measured with synthesized orientation sounds. 5. The equivalent effect of a vocalized orientation sound and a synthesized FM1 component on the activity of FM-FM neurons indicates that, during echolocation, the FM1 component in the vocalized orientation sound stimulates the auditory system and conditions the FM-FM neurons to be sensitive to echoes with particular delays from the vocalized orientation sounds. 6. The amount of vocal self-stimulation to the inner ear by the bat's own vocalized sounds was measured by recording cochlear microphonic potentials (CMs). Spectral analysis of CM indicated that the amount of vocal self-stimulation by each harmonic of an orientation sound was equivalent to a sound of 70 dB sound pressure level (SPL) for the first harmonic (H1), 91 dB SPL for H2, 83 dB SPL for H3, and 70 dB SPL for H4, when the amplitude of the vocalized sound was 117 dB SPL at 5 cm in front of the bat's mouth. PMID- 3351578 TI - Excitatory synaptic actions between pairs of neighboring pyramidal tract cells in the motor cortex. AB - 1. By spike-triggered averaging, we documented recurrent individual excitatory postsynaptic potentials (EPSPs) produced in 33 pyramidal tract (PT) cells (target) by the activity of axon collaterals of neighboring single PT cells (reference) in the motor cortex of the cat. 2. The computer was triggered by the spontaneous activity of reference PT cells or by current pulses applied to reference PT cells through the extracellular recording electrode. 3. The threshold for direct activation of PT cells was less than 0.1 microA with an anodal current pulse and 0.2-0.3 microA with a cathodal current pulse. 4. Application of an anodal current pulse directly activated only a single reference PT cell, the surface membrane of which was presumably touched by and sucked with the extracellular recording electrode. 5. When a cathodal current pulse was used, simultaneous activation of neurons or axons other than the reference PT cell was checked by changing the stimulus parameters along the characteristic strength duration curve for the reference PT cell and/or by comparing averaged EPSPs obtained by cathodal stimulation with those obtained from spontaneous spikes of the reference PT cell. 6. Recurrent individual EPSPs were produced in fast PT cells by activation of neighboring slow PT cells and also of neighboring fast PT cells. Some recurrent individual EPSPs were also observed in slow PT cells. 7. The mean latencies of recurrent individual EPSPs produced by the spontaneous activity of reference slow and fast PT cells were 1.61 (n = 12) and 1.12 ms (n = 8), respectively. Their amplitudes ranged between 30 and 390 microV (n = 33). The rise time observed in fast PT cells with activation of slow and fast PT cells ranged from 1.6 to 3.6 ms (n = 20) and from 0.8 to 1.9 ms (n = 10), respectively. 8. The average conduction velocity of axon collaterals of slow and fast PT cells was estimated to be as slow as that of unmyelinated fibers in the cat. 9. It is suggested that axon collaterals of slow PT cells synapse onto more distal dendrites of fast PT cells than axon collaterals of fast PT cells. PMID- 3351579 TI - Responses of feline trigeminal spinal tract nucleus neurons to stimulation of the middle meningeal artery and sagittal sinus. AB - 1. Extracellular single-unit activity was recorded from 250 trigeminal (V) spinal tract nucleus neurons that were excited by electrical stimulation of the middle meningeal artery (MMA) and/or sagittal sinus (SS) in anesthetized cats. One hundred and thirty of these neurons were located in the V subnucleus caudalis (Vc), and the remaining 120 neurons were located in the V subnucleus oralis (Vo) or rostral part of the V subnucleus interpolaris (Vi). In many cases these neurons were also examined for the existence of orofacial receptive fields (RFs) by applying mechanical stimuli to the orofacial region. 2. The mean minimum latencies to suprathreshold electrical stimulation of the MMA and the SS were similar for Vc and Vo/Vi neurons. Excitation of Vc neurons occurred at latencies of 14.3 +/- 1.0 (n = 102) and 17.4 +/- 1.6 ms (n = 36) to MMA and SS stimulation, respectively. Excitation of Vo/Vi neurons occurred at latencies of 12.4 +/- 0.9 (n = 86) and 16.4 +/- 1.1 ms (n = 58) to MMA and SS stimulation, respectively. These latencies correspond to mean conduction velocities of approximately 5.2 and 4.0 m/s to MMA and SS stimulation, respectively. 3. Mechanical stimulation of the vessels evoked neuronal responses in five of eight MMA-activated neurons tested and three of five SS-activated neurons tested. 4. Almost all of the neurons tested (127 of 131) had peripheral RFs, and all were in the orofacial region. Nearly all (95%) Vc neurons had RFs within or including the ophthalmic facial region. The RFs of most (67%) Vo/Vi neurons also had RFs within or including ophthalmic regions, but in some cases were only within maxillary and/or mandibular regions. 5. Most of the Vc neurons (87%) were classified on the basis of their cutaneous inputs as nociceptive. The incidence of nociceptive neurons in Vo/Vi was also high (61%), although less than in Vc. In both the Vc and Vo/Vi neuronal populations, MMA-activated neurons were more likely to have nociceptive peripheral inputs than SS-activated neurons. 6. Histological reconstruction of recording sites indicated that the MMA- and/or SS-activated Vc neurons were concentrated in the lateral half of laminae III-V. The responsive neurons at the level of Vo/rostral Vi were not confined to any particular portion of these subnuclei. 7. These findings indicate that sensory afferents that innervate the dural arteries and venous sinuses are capable of activating neurons throughout the V spinal tract nucleus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351580 TI - Intracerebral hemorrhage after carotid endarterectomy. AB - A series of 14 patients with intracerebral hemorrhage after carotid endarterectomy is reviewed. This complication occurred in 0.6% of 2362 consecutive carotid endarterectomies performed at the Mayo Clinic from 1972 through 1986. All hemorrhages occurred within the first 2 weeks after operation and were ipsilateral to the side of the operation. Eight patients died, and only two made a good recovery. Significant risk factors are hypertension and chronic hemispheric hypoperfusion with impaired autoregulation. The "normal pressure hyperperfusion breakthrough" syndrome was considered to be operative in 12 of the 14 patients. Nine patients had documented hyperperfusion (at least 100% increase of baseline cerebral blood flow) at the time of surgery. In an additional three patients, normal perfusion-pressure breakthrough was inferred by the clinical course and radiological findings, as well as by the absence of alternative explanations. Patients at risk for postendarterectomy intracerebral hemorrhage include those who have a clinical history suggestive of hemodynamic cerebral ischemia, severe carotid stenosis with limited hemispheric collateral flow, and postendarterectomy hyperperfusion, as measured by intraoperative cerebral blood flow. To minimize the risk of hemorrhage in these patients, strict maintenance of blood pressure at normotensive or even relatively hypotensive levels during the intraoperative and early postoperative periods is advised. PMID- 3351581 TI - Pitfalls in the surgical treatment of moyamoya disease. Operative techniques for refractory cases. AB - Eleven cases of moyamoya disease refractory to indirect non-anastomotic revascularization, including encephalomyosynangiosis in two, encephaloduroarteriosynangiosis in seven, and encephalomyoarteriosynangiosis in two, are described. The patients suffered from recurrent cerebral ischemic symptoms, and further operative intervention, including superficial temporal artery-middle cerebral artery anastomosis and intracranial omental transplantation, was performed. The choice of operative maneuver depended on the availability of scalp arteries and on the nature of the ischemic symptoms. Although indirect non-anastomotic revascularization procedures have the advantage of technical ease and most patients respond to these procedures alone, there are some patients like the 11 presented here who are not cured by such procedures. In such cases, direct anastomotic revascularization is necessary for the prevention of stroke. PMID- 3351582 TI - Unusual spinal cord enlargement related to intramedullary hemangioblastoma. AB - In a series of 60 intramedullary spinal cord tumors, there were eight cases of hemangioblastoma. Seven of these eight patients displayed evidence of diffuse spinal cord enlargement over multiple levels at a considerable range beyond the actual location of the tumor. One patient had a large intramedullary cyst that accounted for only part of the enlargement, and one had multiple tumor nodules. Six other patients had no obvious explanation for the diffuse cord enlargement. This phenomenon of extensive spinal cord enlargement appears to be unique to this type of tumor and not related to multiple tumors or extensive cyst formation. The cord enlargement seems to be related to edema and congestion of the spinal cord, perhaps secondary to the vascular shunt present in the hemangioblastomas. The possible pathophysiology and clinical importance of this observation is discussed. PMID- 3351583 TI - Management of prolactinomas associated with very high serum prolactin levels. AB - The authors have reviewed the results of transsphenoidal microsurgical management in 69 patients with prolactin-secreting pituitary adenomas who had preoperative serum prolactin levels over 200 ng/ml. The patients were divided into three groups based on their preoperative serum prolactin levels: over 200 to 500 ng/ml (Group A); over 500 to 1000 ng/ml (Group B); and over 1000 ng/ml (Group C). The percentage of successful treatment ("control rate") was 68%, 30%, and 14%, respectively, in these three groups of patients. Based on these results, the authors offer guidelines for the management of patients with prolactin-secreting pituitary adenomas associated with exceptionally high serum prolactin levels. The surgical control rate of 68% in Group A seems to justify surgery for these patients, while primary medical care with bromocriptine is recommended for most patients with serum prolactin levels over 500 ng/ml. PMID- 3351585 TI - Nasal encephaloceles: definitive one-stage reconstruction. AB - Nasal encephaloceles can cause complex deformities of the naso-orbital skeleton. As the encephalocele pushes through a defect in the facial skeleton it causes lateral displacement of the medial orbital walls. Correction of this skeletal deformity is necessary to achieve a normal facial contour. Two examples of nasal encephaloceles are presented and the classification, diagnosis, and treatment of this entity are discussed. The correction of these deformities at an early age is recommended. The suggested method of reconstruction is a combined intracranial and extracranial approach with mobilization of the nasal skeleton and medial orbital walls to their normal position. The remaining defects are treated with bone grafts. PMID- 3351584 TI - Serial changes in acute extradural hematoma size and associated changes in level of consciousness and intracranial pressure. AB - The authors report the cases of 37 patients encountered during the past 4 years who exhibited acute extradural hematoma but were initially treated conservatively because no or only small hematomas were observed on admission. The frequency of hematoma enlargement, hematoma size, and changes in the level of consciousness and intracranial pressure (ICP) were examined in these patients. The hematomas enlarged in 24 (64.9%) of the 37 patients, and attained a maximum thickness of 25 mm or greater in 19 patients (51.3%). The level of consciousness could be closely observed during enlargement of the hematomas in 13 patients: the level remained unchanged in eight, deteriorated in two, and improved in three, indicating relative stability in the state of consciousness despite the marked changes in hematoma size. The patients whose hematoma enlarged after the initial examination included three who underwent initial CT examination 5 hours after the injury. In five patients enlargement of extradural hematomas was observed unexpectedly during conservative treatment under ICP monitoring. The ICP also remained stable in three patients until the follow-up examination, but showed a rapid increase in two after a period of stability. However, there was no difference in the final size of the hematomas between the patients showing an increase in ICP and those who did not. These findings suggest that extradural hematomas enlarge progressively at rates varying with the condition of the source of hemorrhage. Moreover, a period of stability in the level of consciousness, such as the lucid interval seen in patients with extradural hematoma, is considered to be a period during which compensatory mechanisms can maintain the stability of the intracranial condition during progressive enlargement of the hematoma. PMID- 3351587 TI - Intracranial pressure and outcome in adult encephalitis. AB - The relationship between intracranial pressure (ICP) and outcome was studied in 10 adults with encephalitis. Eight had biopsy-proven herpes simplex encephalitis, one had acute hemorrhagic leukoencephalitis, and in one case the cause of encephalitis was unknown. Monitoring of ICP was instituted because of clinical deterioration or computerized tomography evidence of brain swelling, and was begun a mean of 7 days after the onset of symptoms and continued for a mean of 9 days. All five survivors, but only one of the five fatalities, had an initial ICP of less than 12 mm Hg (p less than 0.05). Four patients with a mean daily ICP of less than 20 mm Hg survived, whereas five of six patients with higher ICP's died (p less than 0.05). Peak ICP did not occur until the 12th day of illness on average. The Glasgow Coma Scale score at the time the ICP monitor was inserted did not correlate with outcome. Intracranial pressure monitoring in severe encephalitis may be a useful adjunct for therapy and an indicator of prognosis. PMID- 3351586 TI - Posterior cervical reconstruction with methyl methacrylate cement and wire: a clinical review. AB - The charts and radiographs of 20 patients who were treated for traumatic cervical instability by the Department of Neurosurgery at the University of Virginia by means of posterior reconstruction with methyl methacrylate cement and fixation wires were reviewed by the Department of Orthopaedic Surgery. Based primarily on radiographic criteria, it was found that posterior reconstruction failed to rigidly immobilize the underlying unstable motion segments in 11 patients. Four of these patients required additional surgery to correct postoperative instability. Based on this experience, cement and wire reconstructions are now recommended only when: 1) they can be limited to one cervical level; 2) No. 18 fixation wire is used; 3) wiring is performed from a facet on one side to the adjacent spinous processes; and 4) autogenous bone graft is added to the posterior elements on the side of the midline opposite the cement and wire. PMID- 3351588 TI - Cerebral energy metabolism following fluid-percussion brain injury in cats. AB - Clinical and experimental evidence suggests that head injury can cause alterations of cerebral energy metabolism. However, the etiology of this metabolic perturbation is not known. The objective of this study was to determine the effect of fluid-percussion trauma on cerebral energy metabolism. Seven ventilated, chloralose-anesthetized cats were subjected to a 3.2-atm fluid percussion brain injury. Before and for 8 hours after trauma, continuous phosphorus-3 1 magnetic resonance spectrography was obtained to noninvasively monitor tissue pH, phosphocreatine (PCr), and inorganic phosphate (Pi) levels. Measurement of cerebral blood flow (CBF) by the radioactive microsphere technique and calculation of oxygen and glucose consumption (CMRO2 and CMRG1) were also performed before trauma as well as 30 minutes and 1, 2, 4, and 8 hours after trauma. The data showed a moderate decrease in tissue pH from 7.04 to 6.89 at 30 minutes following trauma with return to control levels by 3 hours posttrauma. During the 8-hour observation period, CBF, CMRO2, and CMRG1 remained at control levels. Tissue PCr and Pi levels were also unchanged. Fluid-percussion trauma at the 3.2-atm level in ventilated cats causes a moderate and transient decrease in tissue pH that returns to control levels after trauma. No other metabolic changes are seen later than 30 minutes posttrauma. This indicates that a mild metabolic disturbance occurs after trauma in the ventilated animal and quickly returns to normal. PMID- 3351589 TI - Effect of posttraumatic hypoventilation on cerebral energy metabolism. AB - Cerebral energy metabolism was studied in cats subjected to fluid-percussion brain trauma followed immediately by 30 minutes of controlled hypoventilation for the purpose of simulating a more realistic model of human head injury. The cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2) and glucose (CMRGl) were measured, with simultaneous phosphorus-31 magnetic resonance spectroscopy quantifications of cerebral tissue pH, phosphocreatine (PCr), and inorganic phosphate (Pi). Hypoventilation alone did not produce marked changes in CMRGl, tissue pH, or PCr:Pi ratios. When hypoventilation was combined with trauma, marked alterations in CBF, CMRGl, PCr:Pi ratio, and tissue pH were seen, indicating relative ischemia. The alterations of cerebral energy metabolism produced by combining trauma and hypoventilation are more severe than those caused by fluid-percussion trauma alone, and may provide a more realistic model of human head injury. PMID- 3351590 TI - Cerebral microvascular architecture following experimental cold injury. AB - The sequential changes in microvascular architecture following local cold injury in rat brains were studied post mortem by scanning electron microscopy and the vascular casting method. The findings were compared with the results of immunohistochemical studies of injured endothelial cells using the bromodeoxyuridine (BUdR) and anti-BUdR monoclonal antibody technique. Repair of the microvascular architecture had begun by the 3rd day after injury, with hematogenous cells and reactive astrocytes present in the edematous brain participating in the regenerative process. The normal microvascular architecture was reconstructed starting from the edge of the lesion nearest to the brain surface. On the other hand, in the most severely injured part of the brain surface, newly formed microvascular architecture appeared, resembling that of the developing fetal and newborn rat cortex. Seven days after injury, the entire microvascular architecture in the region of the lesion had been reconstructed. PMID- 3351591 TI - Methods for microstimulation and recording of single neurons and evoked potentials in the human central nervous system. AB - An apparatus and technique are described for microstimulation and recording of both slow wave and single neuron (single unit) activities during functional stereotaxic procedures. This method facilitates microstimulation and evoked potential and single unit analysis which, in combination, provide optimum definition of stereotaxic targets in the treatment of functional disorders of the human central nervous system. PMID- 3351592 TI - Radiosensitive hemangiopericytoma of the falx. Case report. AB - A case of a recurrent hemangiopericytoma of the falx which responded well to radiotherapy is reported. The patient was a 58-year-old woman who received a total of 6000 rads of local Linac irradiation over 6 weeks. One year after completing radiotherapy, a computerized tomography scan showed marked regression of the tumor. PMID- 3351593 TI - Prostatic adenocarcinoma metastatic to chronic subdural hematoma membranes. Case report. AB - A case of adenocarcinoma of the prostate metastatic to chronic subdural hematoma membranes is presented. The relevant literature is reviewed and the mechanism of transdural invasion by metastatic tumor cells is discussed. PMID- 3351594 TI - Cavernous hemangioma of Meckel's cave. Case report. AB - A case of a cavernous hemangioma located within Meckel's cave and involving the gasserian ganglion is described in a patient presenting with facial pain and a trigeminal nerve deficit. Although these lesions have been reported to occur in the middle fossa, this is believed to be the first case of such a vascular malformation arising solely from within Meckel's cave. PMID- 3351596 TI - CT-guided needle biopsy. PMID- 3351595 TI - Corynebacterium Group JK pathogen in cerebrospinal fluid shunt infection. Report of two cases. AB - The clinical and laboratory findings in two cases of aerobic Corynebacterium Group JK infection of cerebrospinal fluid (CSF) shunts are described. These organisms have occasionally been reported as a cause of serious infections in man but have not been reported as a cause of shunt infection. In both cases, CSF pleocytosis was limited to 20 or 60 cells with variable protein and sugar values. Fever was a constant finding, frequently accompanied by signs of central nervous system dysfunction. Corynebacterium Group JK organisms are common contaminants of the normal skin flora. When isolated from the blood and/or the CSF of a patient with a CSF shunt who has symptoms and signs compatible with infection, the organism should not be dismissed as a contaminant. A significant feature of this group is its resistance to almost all presently available antibiotics including penicillin, the cephalosporins, and the aminoglycosides. These organisms are, however, sensitive to vancomycin. PMID- 3351597 TI - Monitoring of intracranial pressure. PMID- 3351598 TI - Staged treatment of AVM's. PMID- 3351599 TI - The shaken baby syndrome. PMID- 3351600 TI - Radionuclear measurement of peripheral hemodynamics in selection of vasodilators for treatment of heart failure. AB - In order to select the optimal vasodilator for the treatment of patients with congestive heart failure (CHF), the acute effects of three vasodilators (isosorbide dinitrate (ISDN) 5 mg, nifedipine 10 mg, and prazosin 1 mg) on peripheral capacitance and resistance vessels (CV and RV) were evaluated by a newly devised radionuclear technique (Study 1). Thirty-six patients with chronic CHF were divided into Group A (ejection fraction (EF) greater than or equal to 35%, n = 20, mean EF: 47.2 +/- 6.5%) and B (EF less than 35%, n = 16, mean EF: 24.8 +/- 7.1%). ISDN produced the strongest CV dilatation (25% in both groups). Nifedipine reduced RV tone in Groups A and B (14% and 27%, respectively), and CV tone in Group A (6%). Prazosin had the most prominent effects on both vessels in Group B. From these results, it appeared: (a) ISDN is indicated for the cases with increased CV tone, (b) nifedipine is suitable for those with increased RV tone, (c) in cases of increased tone in both vessels, nifedipine (when EF greater than or equal to 35%) or prazosin (when EF less than 35%) is optimal. To evaluate the validity of this assignment, 49 subjects with CHF were divided into Group 1 (n = 16, increased CV tone), Group 2 (n = 17, increased RV tone), and Group 3 (n = 16, increased CV and RV tone) in Study 2. In Group 1, the changes of all indexes were not significantly different between the subjects treated with optimal drug based on the assignment (subgroup P) and those with a non-optimal drug (subgroup N) after 2 wk of therapy. In Group 2, however, improvements of RV tone, EF, and exercise duration in subgroup P were greater than those in subgroup N (31 versus 10%, 21 versus 0%, 41 versus 14%, respectively). In Group 3, the results were the same as in Group 2 (34 versus 19%, 24 versus 8%, 26 versus 9%). These findings suggested that the selection of the optimal vasodilator based on peripheral hemodynamic evaluation with a newly devised radionuclear technique permits more effective treatment of chronic CHF. PMID- 3351601 TI - Hepatic arterial and portal venous components of liver blood flow: a dynamic scintigraphic study. AB - Assessment of liver hemodynamics can be obtained by analysis of first pass flow studies through the liver and spleen using 99mTc compounds which are not actually trapped by these organs. This study examines new and existing methods for determining the relevant contribution made by the hepatic artery and portal vein to total liver blood flow, from these first pass studies. Eighty-two studies were performed in 56 patients with both normal and abnormal liver function. Using region of interest analysis, time-activity curves were obtained for the lungs, liver, spleen, and left kidney. These curves were analyzed by four different methods. Two of these methods are based upon measurement of the slopes of the uptake and washout curves from the liver and spleen and the other two methods employ deconvolution analysis to permit area measurement under the deconvolved curves as an indicator of blood flow. All four methods showed a small intraobserver variation after reanalysis. In 11 patients who underwent repeat studies, the correlation between the deconvolution based methods (r = 0.79-0.89) was significantly better than that for the slope based methods (r = 0.55-0.58). The deconvolution based methods provided the most significant separation between normals and patients with various liver disorders and would appear to be the most suitable techniques for monitoring the effects of various drugs and surgical procedures on the relative arterial/portal contribution to hepatic blood flow. PMID- 3351602 TI - The three-dimensional localization of internal mammary lymph nodes by radionuclide lymphoscintigraphy. AB - In breast cancer patients, radiation therapy planning must account for individual anatomy to ensure optimal coverage of tumor and internal mammary nodes. To achieve this, three-dimensional radionuclide lymphoscintigraphy (RNLS) was performed in 167 patients by obtaining two images of the nodes using a 30-degree slant hole collimator rotated 180 degrees between images. Analysis of 768 nodes (mean 4.6/patient) visualized from the level of rib 1 through interspace 5 was performed. The number of nodes seen was not a function of patient age. Cross communication to the contralateral node chain occurred in 13.8% of cases. Eighty two percent of nodes were located near the first three ribs and interspaces; 23% were located beyond 3.0 cm from the mid-sternal line. At the level of the radiation beam match line (second rib or interspace), 4.5% of nodes were deeper than 3.0 cm. From rib 3 through interspace 5, 3.9% were deeper than 3.0 cm. Using an idealized tangential field, at least one node would have been missed in 16.2% of patients. Three-dimensional RNLS allows definition and localization of normal sized nodes and ensures that radiation therapy portals can be tailored for each individual under treatment. PMID- 3351603 TI - Accumulation of indium-111-labeled granulocytes in malignant tumors. AB - In a retrospective study of 220 [111In]granulocyte scintigrams from 208 patients, 25 patients had malignant neoplasms. Among these, tumor uptake of 111In activity was observed in ten patients (intense activity in two patients with non-Hodgkin's lymphoma and colonic carcinoma, respectively; moderate uptake in a patient with non-Hodgkin's lymphoma, and in a patient with an ovarian carcinoma; weak activity in three patients with cerebral neoplasms; and activity within otherwise "cold" metastatic lesions of the liver in three patients). Microscopic investigation following specific granulocyte staining revealed the greatest extent of granulocyte infiltration in the tumors which took up 111In activity, emphasizing the importance of tumor granulocyte infiltration as the single most important factor underlying tumor accumulation of 111In activity during [111In]granulocyte scintigraphy. PMID- 3351604 TI - Evaluation of indium-111-labeled anti-fibrin antibody for imaging vascular thrombi. AB - Monoclonal antibody 59D8 developed by Hui et al., binds to fibrin but not fibrinogen. An 111In-labeled Fab fragment of 59D8 was studied in vitro and in animal models to evaluate its potential for imaging thrombi and emboli in man. Rabbits and dogs were used as models for studying thrombus uptake in vivo. Thrombi and emboli up to 4 days old were successfully visualized at 4-24 hr postinjection in five of eight rabbits. In dogs, 0.5-hr-old and 24-hr-old thrombi were successfully imaged at 24 hr in six of eight animals, and 3/6 of these were positive at 3-4 hr postinjection. Thrombus-to-blood ratios in the dogs averaged 7.1 +/- 1.3. The findings suggest this antibody may be useful for imaging thrombi in man. PMID- 3351606 TI - Increased delivery of gallium-67 to tumors using serum-stable liposomes. AB - Gallium-67 chelated to nitrilotriacetic acid was encapsulated in liposomes composed of various phospholipids, and 67Ga delivery potential to the tumor after intravenous injection of these liposomes was examined. Tumor uptake of the liposomes themselves and their stability in the serum were also studied. It was found that liposomes composed of distearoylphosphatidylcholine, diarachidoylphosphatidylcholine, or sphingomyelin with cholesterol (molar ratio of phospholipid:cholesterol, 2:1) could be taken by the tumor effectively and could deliver large amounts of 67Ga to the tumor. They could also give high 67Ga accumulation ratios (tumor to the other tissues). The study of liposomal stability in the serum suggested that the marked 67Ga accumulation in the tumor resulted from the serum stability of the liposomal bilayer, i.e., the stable liposomes in the blood circulation could reach the tumor in large quantities after i.v. injection. These observations indicate that liposomes with an appropriate lipid composition may be an excellent tool to accumulate 67Ga in tumors. PMID- 3351605 TI - Iodine-125 cholesteryl iopanoate for measuring extent of atherosclerosis in rabbits. AB - Rabbits rendered atherosclerotic by mechanical aortic de-endothelialization and 6 wk of cholesterol feeding were administered estradiol-17 beta-cypionate, an anti atherogenic agent in rabbits. These animals were compared to a similar, untreated group and control animals fed a regular non-atherogenic diet. Iodine-125 cholesteryl iopanoate ([125I]Cl), a nonhydrolyzable cholesteryl ester derivative, was administered intravenously at regular intervals throughout the study. Six days after the last dose of [125I]Cl, the animals were scanned with a gamma camera. After animals were killed, tissue distribution of the 125I radioactivity showed a significant decrease of [125I]CI accumulation in the aorta of estrogen treated as compared to untreated, cholesterol-fed animals. However, the accumulation of [125I]CI in the aortas was insufficient to accurately define the presence of atheroma by gamma camera scintigraphy. PMID- 3351607 TI - A new approach to NEMA scintillation camera count rate curve determination. AB - The method of determining count rate curves suggested by the National Electrical Manufacturers Association (NEMA) is based upon a single reference count rate. Inaccuracies in the reference value are propagated to the rest of the curve values. NEMA also requires the measurement of individual attenuation factors for every absorber. Errors can easily occur during the measurement and during the subsequent calculations which utilize these factors. An alternative approach is suggested: count rate curves are based upon at least five low count rate values and the determination of individual attenuation factors is eliminated. Count rate curves are generated from graphs of the 1n of the observed count rate against the number of equally thick copper absorber plates, by back-extrapolation of a line which is fitted to the linear low count rate data. The method was successfully implemented in practice. Agreement was found between the results of the NEMA method and the alternative method suggested. PMID- 3351608 TI - Conjugate view gamma camera method for estimating tumor uptake of iodine-131 metaiodobenzylguanidine. AB - Therapy with [131I]MIBG has produced partial remissions of malignant pheochromocytomas but not all patients respond. Responses correlate with the quantity of radiation delivered. We developed the conjugate-view method of imaging using 131I reference sources of known radioactivity placed on the surface of the patient and standard nuclear medicine equipment (gamma camera and computer), to estimate tumor uptake of [131I]MIBG. Such an estimate is a first step toward calculating radiation absorbed dose. Three different methods of background subtraction were evaluated with an anthropomorphic phantom and in five patients. In phantom results, measured tumor activity decreased exponentially with a half-life in agreement with that of 131I to within 3%. However, in the phantom studies, in which non-tumor activity is zero, no single method of background subtraction is superior. In patients, two background subtraction methods, which take their estimate from regions immediately surrounding or adjacent to the tumor and reference source, are less sensitive to reference source position and appear more accurate than a third method which uses a background region of interest displaced from the tumor. The agreement of the calculated activity concentration (nCi/g) with that measured by counting portions of the excised tumors gives validation to the method. PMID- 3351609 TI - Strontium-89 therapy: measurement of absorbed dose to skeletal metastases. AB - We report measurements of absorbed dose to vertebral metastases in ten patients referred for 89Sr therapy for disseminated prostatic carcinoma. Patients received a tracer dose of 85Sr at the time of 89Sr treatment and metastatic strontium retention was monitored scintigraphically for 6 mo. Metastatic 85Sr activity corrected for tissue attenuation was measured using the conjugate view principle, with special care taken to eliminate errors due to the selection of the metastatic region of interest. Metastatic volume was determined from high resolution CT images, and density inferred from Hounsfield number using the QCT bone mineral calibration of Genant and Cann. The mean absorbed dose was 850 rad/mCi (23 cGy/MBq) with a range from 220-2260 rad/mCi (6 to 61 cGy/MBq). The wide range found was consistent with the variation expected to arise due to differences in strontium renal plasma clearance (range 0.1-11.81/day) and extent of skeletal metastatic disease (varying from two small metastases to a superscan on [99mTc]MDP images) among the patients studied. PMID- 3351610 TI - Iodine-123 iodoamphetamine brain scan in a patient with auditory hallucination. AB - The case of an alcoholic patient with auditory hallucination is reported in which [123I] iodoamphetamine (IMP) brain imaging demonstrated increased accumulation in the left superior temporal lobe which corresponded to the left primary and secondary auditory areas. Thus, IMP brain scans seem to have the potential to objectively localize the brain abnormalities in auditory hallucination. PMID- 3351611 TI - Paget's disease: a cause of photopenic skeletal defect in indium-111 WBC scintigraphy. AB - As an incidental finding in an [111In]WBC scan performed in search of an infectious focus, photon deficient areas were found in several skeletal locations, characterized by bone and gallium scintigraphy and confirmed radiographically as sites of active Paget's disease. The literature concerning cold bone defects in the [111In]WBC scintiscan is reviewed. Loss of marrow component in the bone appears to be the underlying mechanism for such an abnormality. PMID- 3351612 TI - Recommended method for indium-111 platelet survival studies. International Committee for Standardization in Hematology. Panel on Diagnostic Applications of Radionuclides. AB - Radioactive indium (111In) has been introduced as an alternative to 51Cr as a platelet label because of its shorter half-life, higher photon yield and greater affinity for platelets. Furthermore, platelet labelling with 111In is possible at lower platelet counts than with 51Cr. In healthy individuals, the kinetics of simultaneously injected 111In-labeled and 51Cr-labeled platelets are similar. The document describes the technical and analytic aspects of platelet survival determination with 111In-labeled platelets and is intended to supplement the previously published recommendations for platelet survival studies. PMID- 3351614 TI - Gender-related differences in gastric emptying. PMID- 3351613 TI - Indium-111 WBC imaging--false-positive in a simple fracture. PMID- 3351615 TI - The superconducting super-collider: impact on nuclear medicine. PMID- 3351616 TI - Learning style assessment: a new patient teaching tool? PMID- 3351617 TI - Training computer users. PMID- 3351618 TI - A teaching triad: preceptor, learner, management. PMID- 3351619 TI - How effectively does your staff respond in an emergency? A creative approach to an educational program. PMID- 3351620 TI - Definition and selection of nursing roles. PMID- 3351621 TI - Orientation of temporary staff. PMID- 3351623 TI - Overtime payment methods: meeting staffing and staff needs. AB - Leaders in nursing service are examining factors to both attract nurses to their institutions and to retain the nurses in their institutions. The authors discuss one factor which studies have identified as influencing a nurse's decision to remain in a position. This factor is money. A project which provided this incentive at a large acute care facility is described. PMID- 3351624 TI - Developing trauma care systems: a nursing perspective. AB - Emergency medical services (EMS)/trauma care systems offer unique opportunities for nurse administrators in community hospitals and medical centers to encourage a professional practice model for the department of nursing. The development of local and regional EMS/trauma services involves nurse administrators and their staffs in the legislative process; community networking; program planning, operation, and evaluation; and clinical research. This, the first in a series of articles, reviews the history of trauma care in America, explains the process of regionalization and designation as provided for in the proposed federal legislation, discusses appropriate roles and responsibilities for nurse leaders in trauma care systems, and outlines planning and operational functions for nursing departments in designated trauma care facilities. PMID- 3351622 TI - Developing, implementing, and evaluating a leadership-management program for hospital charge nurses. PMID- 3351625 TI - Method of medication administration: effect on error rates. PMID- 3351626 TI - An emerging professional: the quality assurance nurse. AB - A new professional is emerging within nursing administration, the quality assurance nurse. While quality assurance may or may not be a true profession, these nurses share the common duties and needs of an emerging discipline. These needs include identifying their stage of career development and providing opportunities for skill-building, mentoring, and networking. The author discusses how nurse administrators can help develop the quality assurance practitioner. PMID- 3351627 TI - Resource teams: their structure and use. AB - With the current nursing shortage and changing health care climate, nursing administrators are concerned with the effective and efficient use of supplementary staffs such as internal resource teams (RTs) or float pools. This article describes a telephone survey of 20 leading hospitals nationwide, which identified organization structure, personnel use, and the main characteristics of state-of-the-art resource teams. PMID- 3351628 TI - Preparing nurse executives for tomorrow's health management challenges. PMID- 3351629 TI - Tracking cost while keeping quality alive (and well). PMID- 3351630 TI - Mitochondrial function in rats is affected by modification of membrane phospholipids with dietary sardine oil. AB - Phospholipids of heart and liver of rats fed a diet containing sardine oil had more omega 3 polyunsaturated fatty acids and less omega 6 polyunsaturated fatty acids than those of rats fed corn oil, whereas there was little difference in the fatty acid composition of brain phospholipids. The mass of phospholipid classes in rat heart mitochondria was not changed, but their fatty acid compositions were altered. Modification of the fatty acid compositions of mitochondrial phosphatidylcholine and phosphatidylethanolamine reached a plateau after 10 d of feeding, but that of cardiolipin continued for 30 d. The O2 consumption rate of rat heart mitochondria decreased as the fatty acid composition of the phospholipids changed. This may be due to the reduction of the activity of cytochrome c oxidase, which requires cardiolipin for its activity. However, F1F0 ATPase, which also requires cardiolipin, was activated under the same conditions. PMID- 3351631 TI - Effects of dietary excesses of the branched-chain amino acids on growth, food intake and plasma amino acid concentrations of kittens. AB - The effect of excesses of the branched-chain amino acids (BCAA), particularly leucine, on growth, food intake and plasma amino acid concentrations were investigated in kittens. Effects of excess leucine were tested in kittens fed five basal diets that varied in their nitrogen and amino acid contents. Compared to rats, kittens were much less sensitive to excesses of the BCAA. Addition of 10% leucine to basal diets that provided nitrogen just at or below the minimal requirement of kittens resulted in no change or increased growth and food intake of kittens when the isoleucine and valine concentrations in the basal diet were just at or slightly in excess of the kitten's minimal requirements for those amino acids. An adverse effect of leucine added to low nitrogen basal diets was observed only when isoleucine and valine were provided below the kitten's requirement (80% of requirement). When basal diets containing adequate nitrogen (24% amino acids) were tested, the addition of leucine (10%) resulted in an adverse effect when isoleucine and valine were provided at 80% of the kitten's requirement and in mild growth depressions when isoleucine and valine were provided at 1.1 times the requirement. Leucine-induced growth depression was alleviated by the addition of isoleucine and valine at 0.5%, indicating that excess leucine caused a BCAA antagonism or an amino acid imbalance. With the addition of leucine to the basal diets, there were consistent decreases in concentrations of alanine and tyrosine in plasma but no consistent depressions in the concentrations of isoleucine and valine. PMID- 3351632 TI - Mineral composition and zinc metabolism in female mice of varying age and reproductive status. AB - Zinc metabolism of adult female C57BL/6J mice varying in age and reproductive status was studied using 65Zn. Animals were injected intraperitoneally with isotope, and whole-body and tissue turnover of 65Zn was measured. Biological half life of whole-body 65Zn for pregnant females was 129% of that for nonpregnant, nonlactating females of similar age (25.7 and 20.0 d, respectively). Conversely, the half-life of zinc was less for lactating (11.1 d) and aged (15.3 d) females than for either pregnant or nonpregnant, nonlactating young adult females. Retention of 65Zn was generally lower for all tissues of pregnant and lactating dams than for nonpregnant, nonlactating females except for brain and tibia. In aged females, specific activity at 20 d postinjection did not differ from that of nonpregnant, nonlactating young adult females for any tissue except bone. While specific activity of tibia increased during pregnancy and lactation, it was lower in aged females than in nonpregnant, nonlactating young adult females. Increased organ content of zinc resulted from changes in zinc concentration or in organ mass or both, and was supported by increased food intake. Thus, greater food intake for these groups than for young adult females contributed to the higher turnover of tissue 65Zn. Differences in concentrations of Cu, Ca and Mg were also observed among groups for some tissues; the significance of these differences and their relationship to zinc metabolism are not clear. PMID- 3351633 TI - Retention of skeletal fluoride during bone turnover in rats. AB - Deposition of fluoride (F) in the skeleton is a major factor in the metabolic regulation of F. The progressive increase in bone F levels with age suggests that F is rather firmly sequestered once it is deposited in bone. We have examined the extent to which F is resorbed and redeposited during bone turnover in growing rats. The skeleton was first preloaded with F by intake of water containing a high level of F (50 mg F/L) and simultaneously labeled with [3H]tetracycline (3H TC) to provide a measure of subsequent bone turnover. Rats were then changed to a very low F intake, and bone F loss was compared with 3H-TC loss in animals undergoing normal bone turnover or turnover accelerated by a low calcium (Ca) intake. Approximately 60% of F mobilized during bone resorption was redeposited in the skeleton (humerus and vertebrae). The redeposition of F showed a positive correlation with mineral deposition. Thus the retention of F in the skeleton of growing rats results predominantly from redeposition of resorbed F rather than passive retention associated with low bone turnover. PMID- 3351634 TI - Effect of dietary methionine on utilization of tissue selenium from dietary selenomethionine for glutathione peroxidase in the rat. AB - To study the effect of dietary methionine on the bioavailability of Se from selenomethionine ([Se]Met), weanling rats were first loaded with Se by feeding 0.5 mg Se as [Se]Met per kg diet of a low methionine (0.17% by analysis) torula yeast-based diet for 21 d, and then were fed an Se-deficient diet (less than 0.02 mg Se/kg) supplemented with 0, 0.4 or 0.9% methionine for 28 d. Plasma, liver and muscle Se increased 2.6-, 2.5- and 2.2-fold, respectively, during [Se]Met supplementation, and then the tissue Se declined exponentially during the Se deficient diet period. Plasma, liver and muscle glutathione peroxidase (GSH-Px) activities decreased 43-50% during the [Se]Met supplementation period in spite of the increase in tissue Se. When these [Se]Met-loaded rats were fed the Se deficient diet and supplemented with methionine, tissue GSH-Px activities increased significantly within 3 to 7 d, but then decreased for the remainder of the experiment. Calculation of the percentage of tissue Se present as Se in GSH Px indicated that substantial Se from dietary [Se]Met was stored in tissues in a form different from GSH-Px when a low methionine diet was fed. These results indicate that the dietary methionine level can modulate the availability of Se from dietary [Se]Met and from stored tissue [Se]Met; the inability of stored [Se]Met to provide Se for GSH-Px synthesis over a prolonged period of time suggests that [Se]Met may not be an optimum form for Se supplementation. PMID- 3351635 TI - Nutritional value and safety of methionine derivatives, isomeric dipeptides and hydroxy analogs in mice. AB - Weight gains in mice fed amino acid diets containing methionine and 16 methionine derivatives and analogs were compared at graded dietary concentrations. Linear response was closely approximated for concentrations below those yielding maximum growth. Derivatization of L-methionine generally lowered potency, calculated as the ratio of the slopes of the two dose-response curves. However, the three isomeric dipeptides L-L-, L-D- and D-L-methionylmethionine, N-acetyl- and N formyl-L-methionine, L-methionine sulfoxide and D-methionine were well utilized. The double derivative N-acetyl-L-methionine sulfoxide reduced potency below 60%. D-Methionine sulfoxide, N-acetyl-D-methionine and D-methionyl-D-methionine had potencies between 4 and 40%. The calcium salts of L- and D-alpha-hydroxy analogs of methionine had potencies of 55.4 and 85.7%, respectively. Several of the analogs were less growth-inhibiting or toxic at high concentrations in the diet than was L-methionine. These results imply that some methionine dipeptides or analogs may be better candidates for fortifying foods than L-methionine. Possible biochemical pathways for the utilization of methionine derivatives and analogs are also described. PMID- 3351636 TI - Repression of pentose phosphate pathway dehydrogenase synthesis and mRNA by dietary fat in rats. AB - We have studied the effects of polyunsaturated fatty acid and its metabolism on the activity, relative synthesis and mRNA levels for rat hepatic glucose-6 phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD). Rats were meal-fed high carbohydrate diets containing either no fat, 5% safflower oil or 5% safflower oil + eicosa-5,8,11,14-tetraynoic acid (TYA). Hepatocytes were isolated and used as a source of RNA, de novo radiolabeled protein and postmitochondrial supernatant for enzyme assay. Dietary safflower oil, as a source of linoleic acid, repressed G6PD activity, synthesis and mRNA levels two- to threefold without significantly changing the amount of carbohydrate consumed. Similar but smaller changes were observed for 6PGD. Dietary fat + TYA (an analogue of arachidonate that inhibits normal metabolism of linoleic acid) prevented the fat-dependent lowering of G6PD and 6PGD activity, synthesis and mRNA levels. Our results suggest that a metabolite of linoleic acid regulates the activity of two lipogenic enzymes, G6PD and 6PGD, by lowering gene expression or mRNA processing or stability. PMID- 3351637 TI - Mini x-ray screening for silicosis. PMID- 3351638 TI - Occupational risks for meningiomas. PMID- 3351639 TI - Human and animal risk comparisons. PMID- 3351640 TI - Compliance with mammography recommendations at the work site. AB - Mammography was recommended to 212 women, according to American Cancer Society guidelines, at the time of a work site-offered periodic health exam (PHE). Sixteen weeks later telephone follow-up determined compliance. A total of 56 (26%) had complied. A second phone contact to 82 noncompliers identified 18 additional women who complied after the first phone contact. Overall compliance (36%) was associated with the presence of physical findings upon breast examination (fibrocystic disease). Compliers did not differ from noncompliers with regard to age, time between PHE and follow-up, or insurance coverage. There was no association between compliance and age greater than or equal to 50 years or previous mammography. PMID- 3351641 TI - Monitoring industrial injuries: a case study. AB - This paper presents a new statistical approach for actively using information commonly available in medical surveillance systems to monitor the incidence and severity of industrial injuries on particular operations. The procedures require the practitioner to track the exposure time between injuries. An "out of control" situation is detected when the test statistic exceeds an optimal decision limit, which is determined by minimizing the total injury costs per exposure hour on each operation. The use of this test is presented in the context of a case example from an industrial assembly operation. PMID- 3351642 TI - Chronic occupational exposure to asbestos: more than medical effects? AB - One hundred and twenty-nine workers chronically exposed to asbestos were interviewed regarding their perceived health status and concerns, their health behaviors, particularly their smoking behavior, and their psychologic well-being. In contrast to a non-exposed comparison group of postal workers, asbestos workers exhibited significantly elevated levels of somatic concern (P less than .03), and significantly lower levels of mental health functioning only when experiencing high levels of stress (P less than .01). Despite feeling significantly more susceptible to developing cancer (P less than .0001), 34% of asbestos workers were cigarette smokers (compared to 32% of the postal group) and long-term mask usage was minimal. Asbestos workers' increased sensitivity to stress and changes in health status along with the lack of adaptation of health-promotive behaviors indicate the need for interventions to attend to the psychologic effects of increased risk status. PMID- 3351643 TI - Farming and exposure to chemicals in male lung cancer patients and their siblings. AB - We conducted a retrospective questionnaire study concerning farming and exposure to chemicals on 165 male lung cancer patients, mean age +/- SE, 64.2 +/- 1.0 years, and 165 closest in age male siblings, mean age 64.5 +/- 0.7 years. The patients were diagnosed as having primary lung cancer between January 1, 1979, and November 1, 1983. Among the lung cancer patients, 38.5% had a same-sex sibling eligible for inclusion and of these, 62.0% responded to the questionnaire. Mean pack-years of smoking for patients was 41.0 +/- 2.2 (n = 135) and among the siblings 36.9 +/- 2.4 (118) (P less than .002). The occupation of farming was present in 47.8% of 163 patients with known occupations as compared to 37.6% of 155 siblings with known occupations (not significant). Patients were consistently exposed more frequently to herbicides (P = .05), grains (P less than .015), and diesel fuels (P less than .005), and were consistently exposed to greater numbers of chemicals than were siblings (P less than .005). These findings raise the possibility that, in addition to smoking, farming and related exposures could be implicated in the etiology of lung cancer in men. PMID- 3351644 TI - Treatment of subjects lost to follow-up in the analysis of mortality studies. AB - In the analysis of retrospective cohort mortality studies, persons lost to follow up are either withdrawn at the time of loss or are assumed to be alive at the end of the study. It has been advocated that the former method does not give a biased estimate of expected mortality in this group, and is therefore the preferred method. In this paper, it is argued that this approach is not always the best one, and that in certain situations, depending on the method of follow-up used, assuming that persons lost to follow-up are alive may give more accurate results than withdrawing them at the time of loss. Data from a recent study are used for illustration. PMID- 3351645 TI - Stair climbing: an alternative exercise modality for firefighters. AB - The purpose of this investigation was to determine the maximal cardiorespiratory responses of firefighters to stair-climbing work and to compare these responses to maximal treadmill exercise. Thirty-eight firefighters volunteered to participate in the study. Maximal CR including oxygen consumption (VO2), ventilatory equivalent for oxygen (VE/VO2), minute ventilation (VE) and heart rate (HR) were measured during both stair climbing and graded treadmill exercise. The results showed that VO2max and HRmax were significantly lower, 7% and 2% respectively, and the VE/VO2 was significantly higher (6.7%) during the stair climbing exercise. Maximal VE was not different between the two modes of exercise. The results suggest that since VO2max and HRmax were lower during stair climbing, the metabolic cost of firefighting tasks as related to VO2max on a treadmill may not be accurately reflected. Since stair climbing is a task specific activity for firefighters, it is recommended that testing of firefighters be performed on a stair-climbing device, and that the difference in VO2max between treadmill and stair-climbing exercise be considered when recommending a desired fitness level for firefighters. PMID- 3351646 TI - Neurobehavioral effects of solvents in construction painters. PMID- 3351647 TI - Premenstrual syndrome and sick call utilization among Navy shipboard women. PMID- 3351649 TI - Practice mode of occupational medicine graduates. PMID- 3351650 TI - Intrinsic job stress and diastolic blood pressure among female hospital workers. AB - The present study of 375 female hospital workers assesses the impact of two specific dimensions of vocational stress on standing diastolic blood pressure. Both intrinsic (pertaining to job content) and extrinsic (associated with job context) stressors were examined in this study. Diastolic blood pressure was found to be significantly related to scores on an intrinsic stress measure, but not with the extrinsic one, even after the contribution of obesity and age levels were controlled. However, the effect of intrinsic stress was only found to be significant among women younger than 35. We believe this to be preliminary evidence that perceived dimensions of chronic intrinsic role stressors can be significant psychosocial correlates of diastolic blood pressure. PMID- 3351648 TI - Treatment of subjects lost to follow-up: effect on oil refinery cancer risks. PMID- 3351651 TI - Retinal illuminance using a wide-angle model of the eye. AB - A computer model of relative retinal illuminance, based on our optical wide-angle model of the eye, is proposed for the cases of Ganzfeld illumination and the Maxwellian view through a range of visual field angles from 0 degrees to 80 degrees. The proposed model is designed to be functionally correct and to represent closely the anatomical parameters of the eye. Unlike earlier proposed models, this model is based on our previously reported measurements of spherical aberration in 100 eyes in vivo and is designed to be correct in the peripheral field and with large pupils. Data are reported for pupil diameters of 2, 4, and 8 mm. The effect of crystalline lens extinction on retinal illumination is also estimated for average eyes of young (age 19 years) and old (age 63 years) individuals at two wavelengths (410 and 532 nm). In the Ganzfeld case, illumination of the retina decreases with increasing visual angle. In the Maxwellian view, retinal illuminance increases with increasing visual angle. PMID- 3351652 TI - Tyndall's paradox of hue discrimination. AB - We confirm a remarkable but forgotten property of human color vision that was described over 50 years ago by Tyndall [J. Opt. Soc. Am 23, 12 (1933)]: if wavelength discrimination is measured in the region of 455 nm, the sensitivity of the eye improves when a large fraction of the monochromatic light in each half of the matching field is replaced by white light that is common to the two halves. We demonstrate that a similar facilitation also occurs when the shortwave monochromatic components are held constant in luminance and a long-wave desaturant of increasing luminance is added to the shortwave discrimanda. We relate these phenomena to the properties of postreceptoral visual channels. PMID- 3351653 TI - Birefringence of the human foveal area assessed in vivo with Mueller-matrix ellipsometry. AB - We have assessed retinal birefringence in the foveal and parafoveal regions by applying Mueller matrix ellipsometry on the human eye in vivo. Basically, a light beam passed the ocular media twice and was scattered at the fundus intermediately. Keeping the entry and exit positions on the cornea constant and varying the retinal location along a circle around the foveal center enabled us to separate the corneal and retinal components of the measured retardation. We conclude that the retina within the outer margin of the parafovea behaves as a uniaxial crystal, with its slow axis radially oriented from the fovea and a retardation of about 16 deg (to 70 deg in the corneal center). We believe that Henle's fiber layer causes retardation in this specific configuration of entrance and exit beams. The outer segments of the photoreceptors, although birefringent, have their optic axes aligned with these beams. PMID- 3351654 TI - Relative phases of electromagnetic waves diffracted by a perfectly conducting rectangular-grooved grating. AB - A complete solution of plane-wave scattering from a groove-corrugated surface of infinite extent for arbitrary incidence is presented. The electromagnetic wave is decomposed into fast and slow modal representation, and the solution is accomplished through the use of the mode-matching method. We solved for the zero order diffraction efficiency and the phase of each polarization component for arbitrary incident angles. Our results have verified special cases previously published by others and have illustrated the phase shift between polarizations associated with the diffraction process as a function of the incident angles. PMID- 3351655 TI - The use of lidocaine to reduce the pain induced by potassium chloride infusion. PMID- 3351656 TI - Nursing diagnosis applied to i.v. nursing practice. PMID- 3351657 TI - Care of the cardiac patient: assessment, evaluation, and nursing implications. Part II: Interpretation of laboratory data and hemodynamic monitoring. PMID- 3351658 TI - How much life insurance is enough? PMID- 3351659 TI - Conflict of interest. PMID- 3351660 TI - Nursing implications of patient-controlled analgesia. PMID- 3351661 TI - The management of chronic cancer pain: principles and practices. PMID- 3351662 TI - Therapeutic phlebotomy at home: a case presentation. PMID- 3351663 TI - The femoral arterial flow velocity pattern in patients with lower limb atherosclerosis. Studies with pulsed Doppler ultrasound flowmeter. PMID- 3351664 TI - Characterization of lipid accumulation in the gallbladder mucosa of the ground squirrel fed a lithogenic diet. AB - Richardson's ground squirrels (Spermophilus richardsonii) of both sexes were fed a 2 per cent cholesterol-enriched diet for intervals of 12, 18, and 24 h; 3, 5, and 7 days; and 2, 3, 10, and 20 weeks. It was shown that free (unesterified) cholesterol, phospholipid, and cholesterol ester accumulated in specific regions of the gallbladder mucosa during cholelithiasis. Electron microscopy revealed the presence of lipids inter- and intracellularly as early as 12 h after ingestion. By 7 days, lipids were seen in dilated endoplasmic reticulum, as well as in supranuclear and basal regions of epithelial cells. Histochemical localization revealed free cholesterol in dilated endoplasmic reticulum and residual bodies at the ultrastructural level. Neutral lipid was observed by light microscopy in the supranuclear and basal regions of the cells. In 10- and 20-week treated animals, lipid droplets were also seen in the lamina propria and macrophages. The lesion induced by cholesterol ingestion persisted throughout the experimental period, and while different from that in human tissue, it was similar to those observed in experimental canine cholesterosis. PMID- 3351665 TI - The morphological effects of dexamethasone on the pituitary-adrenal axis of the rat--a quantitative study. AB - Adult Sprague-Dawley rats received a daily intraperitoneal injection of dexamethasone (100 or 200 micrograms/kg) for 2 or 6 weeks. Quantitative assessment of the anterior pituitary corticotroph population performed using the stereological measurement of volume density (Vv). An indirect assessment of corticotroph function was also made, based on adrenal weight and histology. Adrenal changes were consistent with dose-related inhibition of corticotroph function in all dexamethasone-treated animals. Immunopositive corticotrophs were easily identified and in no treatment group was corticotroph Vv significantly less than in the appropriate vehicle-injected control group. In male animals, there was a significant increase (P less than 0.05) in Vv with 100 micrograms/kg at both 2 and 6 weeks. These results suggest that it is possible to produce inhibition of corticotroph function by the administration of such doses of dexamethasone without causing a significant reduction in the anterior pituitary corticotroph population. This may be related to the mode of negative feedback of such a regime. PMID- 3351666 TI - The glomerular tip lesion: a distinct entity or not. PMID- 3351667 TI - Breast carcinoma with stromal multinucleated giant cells. PMID- 3351668 TI - How do we teach pathology? Post-mortems by video. PMID- 3351669 TI - How do we teach forensic pathology? PMID- 3351670 TI - Diagnostic value of DNA flow cytometry combined with fine needle aspiration biopsy in lymphomas. AB - The nuclear DNA content of cells from 45 malignant lymphomas and from 60 benign lymph nodes obtained by fine needle aspiration was analysed to investigate the diagnostic value of DNA flow cytometry combined with routine diagnostic cytology in lymphomas. DNA aneuploidy was found in 43 per cent of lymphomas of high grade malignancy (NCI Working Formulation) but only rarely in lymphomas of intermediate or low-grade malignancy or in Hodgkin's disease, and never in benign lymph nodes. The median percentage of proliferative cells (S + G2/M) was 22.6 per cent in diploid high-grade lymphomas, 15.3 per cent in intermediate-, and 8.1 per cent in low-grade lymphomas, as compared with 4.9 per cent in benign lymph nodes (P less than 0.0001). If the presence of DNA aneuploidy or more than 12 per cent of proliferative cells is used as a criterion for malignancy, the diagnostic accuracy of DNA flow cytometry in detecting lymphoma is 81 per cent. DNA flow cytometry suggested correct diagnosis in 10 of the 19 false positive, false negative, or indeterminate cytological findings encountered during the study. It is concluded that DNA flow cytometry combined with fine needle aspiration biopsy has diagnostic value in lymphomas, but false negative results are common especially in low-grade lymphomas; the method should therefore be used in conjunction with light microscopy. PMID- 3351671 TI - Expression of the 3-fucosyl N-acetyllactosamine (CD 15) antigen in normal, metaplastic, dysplastic, and neoplastic squamous epithelia. AB - The 3-fucosyl N-acetyllactosamine residue is the antigen recognized by the monoclonal antibody MC2. Using MC2, we demonstrated the distribution of this antigen in a variety of squamous epithelia. The antigen is expressed to a variable degree on supra-basal cells in most normal non-keratinizing squamous mucosae, with a similar distribution in metaplastic squamous epithelia; antibody labelled latex microspheres and immunogold electron microscopy show the antigen to form part of the glycocalyx. In dysplastic and neoplastic squamous lesions, expression is reduced or absent except in cells around areas of differentiation. Prior neuraminidase treatment of sections had little effect on the amount or distribution of demonstrable antigen. Expression of this antigen by cells in non keratinizing squamous epithelia gives an indication of cell maturity and may provide a histological marker for the grading of dysplastic and malignant squamous mucosal lesions. A possible role for these carbohydrate residues in squamous mucosal defence is discussed. PMID- 3351672 TI - Lectin expression in carcinoid tumours of the gastrointestinal tract. AB - The binding of peroxidase-conjugated Dolichos biflorus (DBA), Triticum vulgaris (WGA), Canavalia ensiformis (Con A), Arachis hypogaea (PNA), Lotus tetragonolobus, and Bandeiraea simplicifolia I (BSAI) to gastrointestinal carcinoid tumours was studied. The results indicate that carcinoid tumour cells express certain carbohydrates similar to those present in the adjacent surface epithelium. The differences in the lectin-binding properties of carcinoid tumours of different sites of the gastrointestinal tract are closely related to the regional differences in the lectin binding of adjacent surface epithelium. These observations therefore form a useful basis for further studies in the application of lectin histochemistry to elucidate the histogenesis of carcinoid tumours. PMID- 3351673 TI - Desmin-containing stellate cells in the rat liver. PMID- 3351674 TI - How do we teach pathology? The Royal Free Hospital School of Medicine. AB - The teaching of pathology at the Royal Free Hospital has evolved over the past few decades in a stepwise manner, moving away from a didactic lecture- and classroom-based approach to one in which staff time is mainly spent in small group teaching. We present an outline of our current teaching programme in the belief that it differs substantially from that in many other medical schools. PMID- 3351675 TI - Intrapartum asphyxia: a rare cause of cerebral palsy. AB - Data on all children with spastic cerebral palsy (N = 183) and on a matched group of control children (N = 549) born in Western Australia between 1975 and 1980 were compared to investigate the relationship between birth asphyxia and spastic cerebral palsy. Information on perinatal events for both the children with cerebral palsy and the control subjects was collected by means of epidemiologic methods to reduce bias. An association between clinically observed perinatal signs of birth asphyxia and spastic cerebral palsy was found (relative risk 2.84; 95% confidence interval 1.85 to 4.37). The population-attributable risk proportion was 14.1%. The likelihood of birth asphyxia's causing perinatal brain damage was assessed by two independent observers using defined criteria. It was estimated that in only about 8% (15/183) of all the children with spastic cerebral palsy was intrapartum asphyxia the possible cause of their brain damage. The contribution of intrapartum events and obstetric mismanagement to overall cerebral palsy rates is probably less than was previously thought. PMID- 3351676 TI - Minor anomalies in offspring of epileptic mothers. AB - In a prospective study, 121 children of mothers with epilepsy (study group) and 105 control children were examined in a blinded fashion at age 5 1/2 years for 80 minor physical anomalies, including nine typical features previously reported characteristic of fetal hydantoin syndrome. Of the study group, 106 children had been exposed to antiepileptic drugs (82 to phenytoin) during pregnancy; 44 (36%) mothers had had generalized convulsions during pregnancy. One hundred fourteen mothers and 87 fathers of study group children and 101 mothers and 58 fathers of control children were also examined. A significant excess of minor anomalies considered characteristic of hydantoin syndrome was observed in children of epileptic mothers and in epileptic mothers, compared with the control group. There was no excess of other minor anomalies studied. Several minor anomalies previously regarded as typical of fetal hydantoin syndrome were shown to be genetically linked to epilepsy. Only hypertelorism and digital hypoplasia were associated with phenytoin exposure. The current concept of the syndrome seems to be incorrect; most of the "typical" characteristics are not caused by phenytoin. None of the phenytoin-exposed children had all of the main characteristics of hydantoin syndrome (typical acrofacial features, intellectual deficiency, growth retardation, and microcephaly). The risk of developmental disturbance associated with intrauterine phenytoin exposure seems to be much lower than the 7% to 11% risk of fetal hydantoin syndrome reported earlier. PMID- 3351677 TI - Frequency and severity of infections in day care. AB - This study was undertaken to compare prospectively the frequency, nature, and severity of infections experienced by children in three types of child care arrangements: home care, group care (two to six children), and day care (seven or more children). Children were enrolled at birth and observed for 12 to 18 months. At entry there were 159 children in home care, 40 in group care, and 45 in day care. The families were telephoned every 2 weeks to record on a standardized form the type and severity of illnesses experienced during the previous interval. Severe illnesses were defined by high fever, duration exceeding 10 days, or physician visit. Children remaining in their original child care group for at least 1 year were compared with regard to the frequency and severity of illness. Children in group care and day care were more likely than children in home care to experience at least six respiratory infections, more than 60 days of illness, and more than four severe illnesses (P less than 0.01). Similarly, life table analyses showed that children in home care had fewer episodes of infection than did children in day care (P less than 0.01). Although no children were hospitalized because of acute infections during the first year of study, hospitalization for myringotomy and tube placement occurred in 21% of children in day care and 3% of children in home care (P less than 0.01). PMID- 3351678 TI - Prevalence of giardiasis in patients with cystic fibrosis. AB - A group of 107 patients with cystic fibrosis and a control group of 64 normal members of households of patients with cystic fibrosis were surveyed for Giardia lamblia cysts and trophozoites by counterimmunoelectrophoresis of fecal samples. The patient group had a significantly higher rate of infestation than the control group (28.0% vs 6.3%, P = 0.0006), and the disparity between the two groups increased with age (P = 0.005). Aside from cystic fibrosis, all risk factors examined were without influence, except for the presence of household members less than or equal to 5 years of age. We conclude that our patients with cystic fibrosis have a previously unrecognized increased prevalence of giardiasis compared with that in a control population. PMID- 3351679 TI - Chromosome findings and prognosis in 15 patients with neuroblastoma found by VMA mass screening. AB - We performed chromosome analysis of 15 neuroblastomas found by mass screening using a vanillymandelic acid spot test. We found near triploid chromosome abnormalities, ranging from 60 to 77 chromosomes, in the tumor cells from 14 patients, and hyperdiploidy with the mode of 50 in cells from one. A structural abnormality was observed in only one patient. We did not find a marker chromosome 1, homogeneously staining region, or double minutes, which have been previously reported in advanced neuroblastomas or in cell lines. All of our patients were completely free of disease 4 to 32 months after diagnosis. We consider that patients with hyperdiploidy or near triploidy are different from those with marker chromosome 1, homogeneously staining region, or double minutes and may constitute a subgroup with a good prognosis in childhood neuroblastoma. PMID- 3351681 TI - Screening for neuroblastoma. PMID- 3351680 TI - What proportion of cerebral palsy is related to birth asphyxia? PMID- 3351682 TI - A new look at craniometaphyseal dysplasia. PMID- 3351683 TI - Teratogenic effects of anticonvulsant drugs. PMID- 3351684 TI - Treatment of craniometaphyseal dysplasia with calcitriol. PMID- 3351686 TI - Ocular involvement in hemolytic-uremic syndrome. PMID- 3351685 TI - Craniometaphyseal dysplasia with increased bone turnover and secondary hyperparathyroidism: therapeutic effect of calcitonin. PMID- 3351687 TI - Mutant carnitine palmitoyltransferase associated with myoadenylate deaminase deficiency in skeletal muscle. PMID- 3351689 TI - Improving pulmonary function does not decrease oxygen consumption in infants with bronchopulmonary dysplasia. AB - To determine whether the high oxygen consumption VO2 in infants with bronchopulmonary dysplasia (BPD) is caused by increased mechanical power of breathing, and if improvement of pulmonary mechanics would reduce mechanical power of breathing and VO2 we gave 16 infants with oxygen-dependent BPD at 19.5 +/- 10.7 (mean +/- SD) weeks of age placebo, theophylline, and orally administered diuretics or theophylline plus diuretics. Pulmonary mechanics, mechanical power of breathing, and VO2 were measured at the beginning and end of each study period. In the placebo group, all infants had elevated VO2 (7.4 +/- 1.4 mL/kg/min) and carbon dioxide production (6.6 +/- 1.2 mL/kg/min), increased airway resistance (59 +/- 30 cm H2O/L/sec), decreased dynamic compliance (0.073 +/- 0.024 mL/cm H2O/cm), increase respiratory rate (52 +/- 11), and increased mechanical power of breathing (2.22 +/- 1.05 kg.cm/kg/min). Treatment with theophylline, diuretics, and theophylline plus diuretics resulted in a significant improvement in pulmonary mechanics and mechanical power of breathing, but not in VO2. These results suggest that the increased VO2 in infants with BPD is not secondary to increased mechanical power of breathing. PMID- 3351688 TI - Need for endotracheal intubation and suction in meconium-stained neonates. AB - In a prospective study, we determined whether routine immediate tracheal aspiration at birth is necessary in meconium-stained but otherwise normal infants delivered vaginally and having a 1-minute Apgar score greater than 8. A total of 572 newborn infants who met these criteria were randomly allocated to one of two groups. All infants underwent oropharyngeal suctioning with a DeLee catheter while the head was still on the perineum. In group I (n = 308) suctioning of the trachea under direct vision was performed instantly at birth; in group II (n = 264) this procedure was not done. There was no mortality among infants in the study, but morbidity, mainly pulmonary and laryngeal disorders, occurred in six of 308 group I infants and in none of the group II infants (P less than 0.025). Immediate tracheal suction is not a harmless intervention, and should be considered superfluous in a vigorous term neonate born with meconium-stained amniotic fluid. PMID- 3351690 TI - Polyunsaturated fatty acids and protection of newborn rats from oxygen toxicity. AB - To test whether polyunsaturated fatty acids (PUFA) might be associated with protection against oxygen toxicity in newborn experimental animals, we performed two series of experiments. In the first series, adult female rats were fed one of three diets--regular Rat Chow, a high-PUFA (safflower oil-based) diet, or a low PUFA (palm oil-based) diet--for several weeks before and throughout pregnancy and lactation. Newborn offspring of the three diet groups had similar antioxidant enzyme activities and surfactant development. Offspring of dams fed the high-PUFA diet had total lung lipid fatty acids characterized by increased linoleic acid (18:2 omega 6) and arachidonic acid (20:4 omega 6) and a significantly increased PUFA/saturated fatty acid ratio, compared with offspring of dams fed the regular diet or low-PUFA diet; associated with this increased PUFA pattern was markedly superior survival (80 of 84 (95%) vs 56 of 84 (67%) for regular-diet offspring, P less than 0.01) after 7 days in greater than 95% oxygen. Conversely, offspring born to dams fed the low-PUFA diet had decreased lung PUFA content and inferior tolerance to prolonged high O2 exposure (survival 38 of 84 (45%)). In the second experimental series, the postnatal provision of high PUFA rat milk to offspring born to dams fed the low-PUFA diet (via "cross-nurturing" by high-PUFA diet dams) rapidly increased their lung lipid PUFA and improved their hyperoxic survival (44 of 50 vs 25 of 50 for low-PUFA diet newborn animals kept with their low-PUFA mother rats, P less than 0.01). These studies suggest that increasing lung lipid PUFA can confer a protective effect against the toxic effects of hyperoxia on the newborn animal lung. PMID- 3351692 TI - Fetal hydrops and congenital complete heart block: response to maternal steroid therapy. PMID- 3351691 TI - Lipid-laden alveolar macrophage and lactose assay as markers of aspiration in neonates with lung disease. PMID- 3351694 TI - Pharmacokinetics of enprofylline administered intravenously and as a sustained release tablet at steady state in children with asthma. AB - The pharmacokinetics of enprofylline (3-propylxanthine) were studied in 10 children with asthma (mean age 7.9 years), after enprofylline 1 mg/kg given intravenously and after enprofylline 7.5 +/- 1.3 mg/kg given as a sustained release tablet after 8 days of oral dosing twice daily. The mean +/- SD enprofylline serum elimination half-life was 1.06 +/- 0.20 hours, considerably shorter than the half-life reported in adults. The mean steady-state volume of distribution was 0.55 +/- 0.05 L/kg. The mean clearance rate was 0.44 +/- 0.06 L/hr/kg. The mean enprofylline serum concentration at steady state was 1.7 +/- 0.5 mg/L. The mean peak to trough ratio was 3.02 +/- 1.31. On the first and ninth study days, 87% +/- 8% and 90% +/- 16%, respectively, of the dose of enprofylline was recovered as unchanged drug in the urine. Enprofylline has a short half-life in children, but the sustained-release formulation provides stable serum concentrations and satisfactory relief of asthma throughout the 12-hour dosing interval. PMID- 3351695 TI - Determinants of low serum concentrations of salicylates in patients with Kawasaki disease. AB - The mechanisms leading to the previously reported difficulties in achieving therapeutic serum concentrations of salicylates in Kawasaki disease were studied in eight children, once during the acute (febrile) phase and again during the nonfebrile (subacute) phase of the disease. Salicylate bioavailability was impaired during the acute phase of the disease (47.7% +/- 6.6%), and increased significantly thereafter to 75.1% +/- 9.3%. During the febrile phase there was a significant correlation between salicylate bioavailability and steady-state serum concentrations. Salicylate renal clearance was significantly higher during the febrile phase (14.45 +/- 2.5 mL/kg.h), compared with the nonfebrile phase (7 +/- 1.6 mL/kg.h, P less than 0.05). The change in salicylate clearance could be explained by decreased protein binding in the acute phase (82.5% +/- 1.9%) with substantially more free salicylates caused by significantly lower serum albumin concentrations. Changes in urine metabolites during the acute and subacute phases were consistent with the changes in dose administered (100 mg/kg in the acute phase vs 10 mg/kg in the subacute phase). The pattern of metabolites excreted in the urine of children with Kawasaki disease receiving 100 mg/kg was similar to that in children with juvenile rheumatoid arthritis receiving the same dose. PMID- 3351693 TI - Furosemide pharmacokinetics in very low birth weight infants. AB - The pharmacokinetics of furosemide were studied longitudinally during long-term administration in 10 very low birth weight infants with bronchopulmonary dysplasia. Mean birth weight of the infants was 829 +/- 217 g, mean gestational age at birth was 26.6 +/- 2.9 weeks, and mean postnatal age at the start of therapy was 2.4 +/- 1.0 weeks. Serial determinations of furosemide pharmacokinetic parameters were performed during 2 weeks to 3 months of long-term therapy. Plasma half-life was prolonged in infants less than 31 weeks postconceptional age (gestational + postnatal age), frequently exceeding 24 hours. All infants less than 29 weeks postconceptional age whose dosing schedule was once every 12 hours accumulated furosemide to potentially ototoxic levels. Furosemide renal clearance increased and plasma half-life decreased in association with increasing postconceptional age. Furosemide secretory clearance was very low in patients less than 31 weeks postconceptional age, resulting in a reliance on glomerular filtration to deliver drug to its main site of action within the lumen of the loop of Henle. Thus elevated plasma levels may be required to ensure adequate luminal delivery and adequate diuresis in these infants with low secretory clearance. Nevertheless, the current dosing schedule (once every 12 hours) of furosemide should be modified to once every 24 hours in infants of low postconceptional age to avoid possible toxic effects. PMID- 3351696 TI - Cholecystitis in a 17-year-old boy with recurrent jaundice since childhood. PMID- 3351697 TI - Hereditary nephritis and sensorineural deafness. PMID- 3351698 TI - Carnitine in lactic acidosis. PMID- 3351699 TI - Incidence of gastroesophageal reflux in sleep, awake, fasted, and postcibal periods in asymptomatic and symptomatic infants. AB - The incidence of gastroesophageal reflux (GER) in infants has been shown to be dependent on different factors, e.g., position, feeding, age. Using continuous esophageal pH monitoring, we examined 30 asymptomatic (15 were 1.5-2.5 months old; 15 were 2.5-4.5 months old) and 20 symptomatic infants (1.5-4.5 months old) for GER. The occurrence of GER was analyzed in different periods of interest: awake, asleep, fasted, and postcibal periods. The increasing incidence of GER we reported previously in asymptomatic infants according to their age appeared to be due to an increased occurrence in the awake (and postcibal) periods. In symptomatic infants, however, the increase was noticed mostly during the sleep (fasted) periods as far as the reflux index, the duration of the longest reflux episode, and the number of reflux episodes of greater than 5 min are concerned. PMID- 3351700 TI - Gastric emptying in infants: response to metoclopramide depends on the underlying condition. AB - In a double-blind, placebo-controlled, randomized study we measured the effect of 1 mg/kg intravenous metoclopramide on the gastric emptying of a 15 ml/kg 5% glucose meal, using a phenol red dye dilution technique. In a group of nine infants referred for multiple daily episodes of regurgitation, metoclopramide doubled the rate of gastric emptying (p less than 0.02). In six infants with prolonged gastroparesis following abdominal surgery, metoclopramide more than doubled the rate of gastric emptying (p less than 0.05). In contrast, in seven infants with gastroparesis related to prematurity, metoclopramide did not significantly change gastric emptying. No extrapyramidal side effects of metoclopramide occurred during the study. PMID- 3351701 TI - Effect of feeding volume on early postcibal gastroesophageal reflux in infants. AB - Using esophageal pH monitoring, we have investigated the effect of feeding volume on early (1 h) postcibal gastroesophageal reflux (GER) in a population of 50 infants referred for evaluation. Two feedings with the volume of both feedings specified (9 and 18 ml/kg) were given to one group of infants. A second group was given one feeding ad libitum and another specified at 9 ml/kg. Volume of intake was a very significant determinant of both the total duration and the maximum single continuous episode of GER during early postcibal esophageal pH monitoring in both groups by paired analyses. This effect was observed in infants with significant GER (n = 44) and in a subgroup of infants who were normal (n = 6). PMID- 3351702 TI - Absorption of medium chain triglycerides in the stomach of the human infant. AB - Following previous observations that medium chain triglycerides (MCT) are absorbed from the stomach of suckling rats, this study was devoted to studying absorption of MCTs in human infants. Four groups of patients were studied: (a) infants suffering from pyloric stenosis, (b) premature infants, (c) children suffering from cystic fibrosis, (d) infants with miscellaneous conditions. Infant formulae with known amounts of MCT were introduced by gastric tube and samples were removed at 0, 20, 40, and 60 min. In patients with pyloric stenosis there was an 18.1% decrease in MCT during the first 20 min. No significant changes in MCT took place during the subsequent 40 min. A similar response was observed in the group of premature infants. Older infants with miscellaneous diagnoses and children with cystic fibrosis showed an even rate of disappearance of MCT during the 60-min test period, and approximately 30% of the original MCTs present disappeared during this period. We conclude that MCTs are absorbed in the stomach of infants and children. Absorption appears to improve with age. Because MCT are an important constituent of formulae for premature infants and children with defects of small intestinal digestion and absorption of fat, these observations have practical implications. PMID- 3351703 TI - Handling of gliadin peptides B1-B4 and of cow's milk proteins by rat jejunum gut sacs. AB - The rat everted gut sac was used as a model of intestinal protein and peptide handling to study small intestinal binding and uptake of different gliadin peptide fractions (B1, B2, B3, B4) in comparison with bovine serum albumin (BSA), alpha-lactalbumin (alpha-LA), and a BSA peptide fraction (BSA-P). Not only binding curves, but also uptake curves of BSA, alpha-LA, and BSA-P were run in parallel between 1 and 30 min. Binding and uptake obviously depended on molecular weight. BSA-P binding was found to be highest of all. Binding of BSA was significantly lower. After 20 and 30 min, significantly more alpha-LA and BSA-P were taken up than was BSA. There was no difference in handling of the gliadin peptide fractions tested by the gut mucosal surface. Binding of B1-B4 was significantly higher than binding of BSA and was significantly lower than binding of BSA-P. No difference was found between binding of B1-B4 and alpha-LA. There was a consistently higher uptake of all gliadin peptide fractions, independent of molecular weight. Slopes for uptake curves of B1-B4 were steeper than those of BSA, alpha-LA, and BSA-P. Crossing of uptake over binding curves was consistently observed with gliadin fractions, but never with cow's milk proteins/peptides. Differences in uptake between gliadin peptide fractions and cow's milk proteins/peptides might be based on a specific interaction between gliadin peptides and the gut surface. PMID- 3351704 TI - The effect of feeding four different formulae on stool weights in prolonged dehydrating infantile gastroenteritis. AB - Prolonged diarrhea following an acute episode of dehydrating gastroenteritis in infants is often treated by the empirical removal of both cow's milk protein and lactose from the feed, as they both have been implicated in the prolongation of diarrhea. In order to assess the efficacy of this policy and to determine whether there are any advantages in using a lactose-free semi-elemental feed in this situation, infants with prolonged dehydrating gastroenteritis from a developing community in South Africa were studied. Male black children between the ages of 6 weeks and 2 years with prolonged dehydrating gastroenteritis (requiring intravenous fluids for longer than 72 h to maintain hydration) were randomly assigned to receive one of four feeds if the stool weight was greater than 30 g/kg body weight/24 h on the fourth day of admission. The four formula feeds were a partially modified cow's milk formula; a lactose-free, casein-containing formula; a lactose-free, soy-protein-containing formula; and a lactose-free, whey hydrolysate-containing formula. Stool weights were measured for the following 3 days. Seventy-two children were enrolled into the study. Stool weights were similar in the four groups at the start of the trial, and fell significantly over the trial period in those groups receiving the lactose-free feeds. Mean stool weight in the cow's milk formula group did not change. Thus, it appears that the continued feeding of a cow's milk-based lactose-containing formulae to infants with prolonged dehydrating gastroenteritis adversely affects their recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351705 TI - Comparison of a lactose-free cereal-based formula and cow's milk in infants and children with acute gastroenteritis. AB - Sixty children less than 2 years of age suffering from mild acute gastroenteritis with less than 5% dehydration were randomly assigned to two different isocaloric feeding regimens, viz., a locally prepared milk-free formulation (group A) of rice, lentil, sugar, and coconut oil and a spray dried commercial cow's milk formula (group B). There were two treatment failures in group A and one in group B. The postintervention duration of diarrhea (days) in group A (11.0 +/- 10.0) was higher than in group B (7.6 +/- 10.8), but these differences were not significant (p greater than 0.05). The energy intake (kcal/kg/24 h) on postintervention day 4 was 78.7 +/- 31.7 in group A and 101.3 +/- 41.1 in group B (p greater than 0.05). The corresponding values for day 7 were 74.2 +/- 29.1 and 110.0 +/- 41.1, respectively (p less than 0.05). The mean weight gain (g/kg/24 h) between admission and the day of recovery in group A (2.0 +/- 4.2) was significantly lower (p less than 0.05) than in group B (5.8 +/- 7.8). Similar trends in weight gain were observed at days 4 and 7. These findings suggest that a cow's milk-based formula is well tolerated by majority of the infants with mild acute gastroenteritis after initial rehydration with ORS. The infants who were fed the milk-free cereal-based diet showed significantly less energy intake and gained weight less rapidly than those who were fed the cow's milk-based formula. PMID- 3351706 TI - Excessive fecal taurine loss predisposes to taurine deficiency in cystic fibrosis. AB - Elevation of the ratio of glycine: taurine-conjugated bile acids (G/T ratio) is thought to contribute to fat malabsorption in cystic fibrosis (CF). The cause, extent, and reversibility of taurine deficiency in CF were assessed using balance studies in 6 subjects (ages 8-14 years) who were supplemented with taurine (0.24 2.4 mmol/kg/24 h) for 1 week. Taurine reduced the G/T ratio both in serum and duodenal juice in all children. The mean fecal taurine loss in CF subjects [10.8 mumol/kg/24 h +/- 9.9 (SD), range 0.9-27.9] was much greater than that in controls (less than 0.1 mumol/kg/24 h, n = 4) and approximated the dietary taurine intake (mean 14.6 +/- 4.4 mumol/kg/24 h, n = 12). Absorption of an oral taurine load appeared to be normal in CF. Excessive fecal taurine loss appears to predispose CF children to bile acid taurine deficiency, a deficiency that can be corrected by oral taurine supplements. PMID- 3351707 TI - L-carnitine supplementation of a soybean-based formula in early infancy: plasma and urine levels of carnitine and acylcarnitines. AB - The absence of carnitine in the diet of normal infants results in marked reduction of plasma carnitine levels. In order to evaluate the effects of L carnitine supplementation of soybean formula, plasma and urine levels of free carnitine and acylcarnitine were compared in infants receiving carnitine-free soybean protein-based formula and the same formula supplemented with 50 and 250 nmol/ml L-carnitine. In infants receiving soybean formula with 50 nmol/ml L carnitine, the plasma levels of free carnitine were not significantly different from those in infants receiving formula with 250 nmol/ml L-carnitine; however, urine levels of free carnitine were significantly increased when the infants received formula with 250 nmol/ml L-carnitine. In normal full-term infants, supplementation of soybean formula with 50 nmol/ml L-carnitine was sufficient to maintain normal plasma levels that were comparable to breast-fed infants. PMID- 3351709 TI - An unusual presentation of pancreatic carcinoma in childhood. AB - Carcinoma of the pancreas is rare in the pediatric population, with only 58 cases described in subjects under 16 years of age. The clinical presentation generally consists of abdominal pain and mass. We present a case of carcinoma of the pancreas in an 11-year-old girl, with abdominal pain and unusual behavior. PMID- 3351708 TI - Infrared analysis for determining macronutrients in human milk. AB - Infrared (IR) analysis is widely used for routine analysis of cow milk in dairies. The aim of this study was to evaluate the precision and accuracy of an IR analyzer (Milko-scan 104) for measuring protein, fat, carbohydrate, and, indirectly, the energy content of human milk. The results of the IR analysis were compared with those of the following reference methods: protein--Kjeldahl (nitrogen minus nonprotein nitrogen); fat--Roese Gottlieb; carbohydrate--lactose enzymatic assay; energy--bomb calorimetry. The precision (repeatability coefficient of variation) of the IR results was high for all four components: protein 0.4%, fat 1.0%, carbohydrate 0.2%, and energy 0.1%. There was a close linear covariation between IR results and reference results. [Protein content was determined with an error (SD) of 0.01 g/100 ml and fat with an error of 0.03 g/100 ml.] The covariation between IR carbohydrate results and the results of the lactose assay was poor, probably because the oligosaccharides in the milk were included in the results from the IR analysis and not in the results from the lactose assay. IR analysis is a valuable method in research, especially in epidemiological surveys, in which large numbers of samples are analyzed, and for continuous monitoring of the nutritional value of human milk in milk banking programs. PMID- 3351711 TI - Familial extrahepatic biliary atresia. AB - Only a small number of cases with familial extrahepatic biliary atresia, suggesting a recessive autosomal inheritance, have been reported. However, the cases reported in twins are consistent with an acquired disease. Here the case of two brothers with familial atresia of the extrahepatic biliary system is studied. Diagnosis was confirmed by laparotomy and histologic study of biliary fibrous remnants. In the present cases parental consanguinity might suggest a recessive autosomal inheritance. However, clustering of cases in a family might also suggest a common exposure to responsible factors not so far identified. PMID- 3351710 TI - Pancreatic function testing in meconium disease in CF: two case reports. AB - We report two infants with cystic fibrosis (CF), presenting with meconium ileus and meconium plug, who had no clinical or biochemical evidence of pancreatic insufficiency during infancy. They underwent pancreatic secretory function testing at 11 and 9 months of age, respectively. Both patients had sufficient lipase and colipase secretion to maintain normal digestion of fat, confirming that meconium disease in CF does not necessarily imply pancreatic insufficiency and the need for enzyme supplementation in infancy. Nonetheless, we documented markedly reduced enzyme secretion in both patients, implying a potential role for the pancreas in the pathogenesis of meconium disease, even when clinical pancreatic insufficiency is absent. In addition, our patient with meconium ileus had a severely limited fluid secretory capacity (10.3% of mean normal values). In contrast, the patient with the milder presentation of meconium plug had a far greater ability to secrete fluid (75% of mean normal), but had poorer pancreatic proteolytic activity. We suggest that impaired fluid secretion may be a very significant factor in the pathogenesis of meconium ileus, and we speculate that an inability to maintain sufficient intraluminal fluid relative to the degree of pancreatic proteolytic deficiency may more adequately explain the risk of occurrence and the severity of intestinal obstruction in CF than either factor alone. PMID- 3351712 TI - Familial achalasia with absent tear production. AB - Three of five siblings were evaluated because of dysphagia and failure to thrive. Radiologic and manometric studies were consistent with achalasia of the cardia. All of these siblings had deficient tear production. This report documents the unusual association of familial achalasia and deficient tear production, which is probably an autosomal recessive inherited syndrome. PMID- 3351713 TI - Acetylcholinesterase activity in rectal biopsies: an assessment of its diagnostic value in Hirschsprung's disease. PMID- 3351714 TI - Use of a balanced lavage solution in the treatment of fecal impaction. PMID- 3351715 TI - Pyloric stenosis and eosinophilic gastroenteritis in infants. PMID- 3351717 TI - Prognosis of nonsyndromic paucity of intrahepatic bile ducts. PMID- 3351716 TI - About methemoglobinemia. PMID- 3351719 TI - Intercostal pedicled flap in esophageal atresia. PMID- 3351718 TI - Intestinal permeability to lactulose/L-rhamnose in children with celiac disease and other gastrointestinal disorders. PMID- 3351720 TI - Feeding in neonatal necrotizing enterocolitis. PMID- 3351721 TI - Whole bowel irrigation in pediatric patients. PMID- 3351722 TI - Alleged resection of the vas deferens: medicolegal implications. AB - New York state law requires that significant complications be reported by telephone within 24 hours, followed by a full written report within five days with the names of the alleged involved physicians. This case illustrates the potential medicolegal consequences following the mandated immediate nonsubstantiated report of an alleged bilateral vas deferens injury during a bilateral inguinal herniorrhaphy in a 7-month-old male. Review of the surgical pathologic specimen showed that both hernial sacs did indeed contain segments of vas deferens structures, which based on the findings at reexploration, were consistent with duplication or embryonic remnants of the vas deferens. The vas deferens was found to be normal and uninjured bilaterally. The legal ramifications remain unclear. Since there is no clear cut method to retract the allegation, the physician's profile may be permanently damaged. PMID- 3351724 TI - Papers presented at the 18th annual meeting of the American Pediatric Surgical Association. Part 2. PMID- 3351723 TI - "Waterseal" gastrostomy in the management of premature infants with tracheoesophageal fistula and pulmonary insufficiency. AB - The perioperative management of premature infants with esophageal atresia and tracheoesophageal fistula (EA/TEF) complicated by pulmonary insufficiency continues to be a challenge. Definitive repair is usually delayed or staged and a gastrostomy is initially placed to prevent reflux aspiration. In patients with decreased pulmonary compliance, gastrostomy placement results in decreased intragastric pressure leading to a loss of ventilatory pressure via the tracheoesophageal fistula. A technique using the principle of underwater seal to maintain effective ventilatory pressure after gastrostomy placement is described, and two illustrative cases are presented. After acute respiratory decompensation in these patients, the gastrostomy tube was connected to underwater seal resulting in improved respiratory status. The underwater seal is allowed to intermittently "bubble," thereby permitting partial gastric decompression. This technique maintains effective ventilatory pressure after gastrostomy placement in premature infants with EA/TEF and pulmonary insufficiency until definitive therapy can be achieved. PMID- 3351725 TI - Extended four-channel esophageal pH monitoring: the importance of acid reflux patterns at the middle and proximal levels. AB - Seventy-one extended multiple-level esophageal pH studies were performed in 61 infants and children suspected of having gastroesophageal reflux (GER). The patients were placed in one of six clinical groups based on their presenting symptomatology. They were classified as "normals" or "refluxers" based on a reflux score calculated from a pediatric modification of the Johnson and DeMeester distal esophageal pH criteria. For the total group, excluding postoperative patients, all differences noted in the distal esophagus between normals and refluxers persisted at the middle and proximal esophageal levels (P less than .001). Significant differences between normal and reflux patients were noted at all levels in the central nervous system damage and postoperative groups. Only the middle esophageal probe detected differences for all variables in the failure to thrive group (P less than .01). In the esophageal atresia group the middle level sensor detected differences in all parameters studied and the proximal sensor noted differences in three of the four parameters (P less than .01). Significant differences between normals and refluxers in the apnea group were best demonstrated in the proximal esophagus. There was no benefit in monitoring the pH of the more proximal esophageal levels in patients with esophagitis. Extended four-channel esophageal pH studies were highly effective in detecting clinically important GER. The patterns of reflux in infants and children vary markedly with the presenting symptoms. Distal esophageal pH monitoring may not demonstrate evidence of GER that would otherwise be detected by the middle and proximal esophageal sensors. This new ambulatory outpatient technique of pH monitoring in young patients suspected of having GER provides advantages over the conventional esophageal pH study. PMID- 3351726 TI - Imperforate anus with long but apparent low fistula in females. AB - Despite the low entry of the rectum into the vagina in some females with imperforate anus, the fistula may be deceivingly long. This variation should alert the surgeon to measure the fistula prior to anoplasty. During surgery, biopsies of the mobilized segment should also be done to assure that cloacal transitional lined structures have been removed and rectal mucosa anastamosed to the perineum. PMID- 3351727 TI - Alternative operative procedure for total colonic aganglionosis. AB - The authors have utilized a technique recently described by Boley as the corrective procedure in two patients with complex long segment aganglionosis. The one-stage operation combines a right colon onlay patch for enhanced absorptive and reservoir purposes with an ileoendorectal pull-through. Both patients had only 3 to 4 stools per day by the end of the first postoperative month. The obligatory period of intestinal adaptation needed to achieve an acceptable stooling pattern is significantly reduced in comparison with results obtained with other commonly used procedures. PMID- 3351728 TI - Extensive aganglionosis: further experience with the colonic patch graft procedure and long-term results. AB - During the period from 1979 to 1986, seven patients have been treated for extensive aganglionosis involving the colon and distal ileum (5 to 40 cm) employing the colonic patch graft (CPG) procedure. This consists of (1) ileostomy; (2) creation of a longitudinal side-to-side ileocolostomy between normal ileum and aganglionic ascending colon, forming a CPG; and (3) the definitive pull-through procedure. In all patients, the initial course after ileostomy was complicated by severe diarrhea, which was significantly improved by creation of the CPG. At the definitive operation several months later, the mesocolon attached to the CPG was severed to mobilize the ileocolostomy segment to the distal pelvis. Four patients in this series have been followed for 5 to 8 years. No patient has developed enterocolitis requiring hospitalization. Body weight became normal for age in all patients within 4 years of the definitive operation. PMID- 3351729 TI - Multifocal ganglioneuroblastoma coexistent with total colonic aganglionosis. AB - Neuroblastoma and Hirschsprung's disease are considered aberrations of neural crest cell growth, migration, or differentiation. Their coexistence, however, is rare. We present the case of an only child with total colon Hirschsprung's disease diagnosed shortly after birth, who was found to have noncontiguous ganglioneuroblastomas without metastases at age 16 months. The spectrum of neural crest anomalies, long segment Hirschsprung's disease and multifocal neuroblastoma, in this child is unique and previously unreported. PMID- 3351730 TI - The role of coagulase-negative Staphylococcus in neonatal necrotizing enterocolitis. AB - Coagulase-negative Staphylococcus has emerged as a prominent pathogen in the neonatal intensive care unit and a recent report has implicated this organism in necrotizing enterocolitis (NEC). This same study suggests that Staphylococcus epidermidis is most commonly associated with a "mild form of enterocolitis." This prompted a review of the role of coagulase-negative Staphylococcus in the surgical complications of NEC. Between 1982 and 1986, 86 newborns underwent operation for perforation or intestinal necrosis secondary to NEC. Blood cultures, obtained within 72 hours of surgery, were positive in nine of 71 infants (13%). One third of these grew coagulase-negative Staphylococcus. Peritoneal cultures obtained at the time of operation were positive in 71 neonates. The incidence of Staphylococcus epidermidis was 30%. In a third of these cases, coagulase-negative Staphylococcus was the only organism covered. Overall mortality within the group was 33%. Coagulase-negative Staphylococcus was the single most frequent organism recovered from those infants who expired (35%). This data clearly indicates that Staphylococcus epidermidis must be considered as a significant pathogen in NEC. It is associated with both morbidity and mortality and, therefore, warrants appropriate aggressive therapy when recovered from the neonate with enterocolitis. PMID- 3351731 TI - Resection with primary anastomosis for necrotizing enterocolitis: a contrasting view. AB - Resection with primary anastomosis is currently being advocated for treatment of infants with necrotizing enterocolitis. To determine whether our own data would support such an approach, we reviewed retrospectively our experience with this disease since 1974. Since that time, 173 infants have been admitted for treatment of advanced (surgical) disease in its acute phase, of whom 143 underwent resection for cure; the remainder either underwent laparotomy with decompression (3), laparotomy with drainage (3), laparotomy alone (14), died at operation (1), or could not be resuscitated sufficiently to withstand operation (9). Excluded were patients who underwent operative repair of late stricture (6), all of whom survived with no morbidity. Among those resected for cure, 27 infants were carefully selected by the operating surgeon for treatment by means of resection with primary anastomosis, based on the limited and apparently discrete nature of their disease; in three the procedure was combined with a decompressing enterostomy. In the majority of cases (14), the disease was found to involve multiple areas of intestine, but was limited to a particular anatomic region, usually distal ileum and/or ascending colon; in the remainder, it was due to discrete ileal or jejunal perforation or ulcer. Overall survival among those resected for cure was 65% (96/143). It was 48% (13/27) among those treated by means of resection with primary anastomosis but 72% (83/116) among those who underwent resection with enterostomy. However, if the early years of the series (1974 to 1976) are excluded, a time when resection with enterostomy had not yet become established as standard therapy, overall survival was 77% (77/100), 64% (9/14) among those anastomosed primarily. PMID- 3351732 TI - Time-lapse photography: a novel tool to study normal morphogenesis and the diseased hepatobiliary system in children. AB - The etiology of biliary atresia (BA) and many other childhood cholangiopathies remains unknown. To investigate the normal and diseased hepatobiliary system in vitro, we isolated and cultured biliary epithelial cells (BEC) from a number of species including man. Time-lapse video microscopy was used to study cell movements in vitro, and demonstrated the characteristic morphologic appearance of the BEC and their interactions with hepatocytes and other cell types on artificial biosynthetic materials. The cells remain attached and viable in routine culture conditions; however, when placed onto or within a source of extracellular matrix, the cells move off the surface and form characteristic morphologic patterns, which on time-lapse video are consistent with tube or duct formation. These findings suggest that time-lapse photography may be a useful tool for in vitro studies of normal morphogenesis of the hepatobiliary system and may enable us to better understand biliary atresia and other childhood cholangiopathies. PMID- 3351733 TI - Staging the separation of ischiopagus twins. AB - A pair of ischiopagus tetrapus twins were successfully separated in Calcutta in 1986. The separation was staged. The gastrointestinal tracts were separated at a preliminary operation, and definitive separation carried out 3 months later. Staging permitted us to perform the final separation on healthier babies with the exclusion of the intestinal contents from the wounds and with reduced operating time. PMID- 3351734 TI - High proximal pouch esophageal atresia with vertebral, rib, and sternal anomalies: an additional component to the VATER association. AB - The base of the proximal esophageal pouch in babies born with esophageal atresia varies in location from the low cervical region to the upper third of the mediastinum, but the relevance of this finding to the VATER association is not known. The initial radiographs and hospital records of 42 newborns with esophageal atresia and a distal tracheoesophageal fistula treated in the Newborn Special Care Unit of the Yale-New Haven Hospital between 1977 and 1986 were examined to (1) determine the location of the base of the upper esophageal pouch on its superimposed vertebral body; (2) identify coexisting VATER associated anomalies; and (3) detect the presence of vertebral, rib, or sternal anomalies. Ten of 11 babies with the upper esophageal pouch at the first thoracic vertebra or above had additional VATER defects including vertebral, rib, or sternal anomalies. These patients also required staged repair or circular myotomy for wide gap esophageal atresia and were at greater risk of anastomotic leak, stricture, or gastroesophageal reflux requiring fundoplication. High proximal pouch esophageal atresia accompanied by vertebral, rib, and sternal anomalies constitutes a heretofore unrecognized high risk group with the VATER association. PMID- 3351735 TI - A model to study the direct effect of diet on early intestinal growth and maturation using Thiry-Vella loops. AB - Thiry-Vella loops (TVL) are neurovascular intact intestinal segments isolated from the normal flow of chyme. TVL have been used to assess the effects of local and systemic factors in the intestine of adult animal models. To assess the direct effect of diet in growth and maturation of the intestine in the growing animal, the authors developed a similar model in the weanling rat. The surgical technique is described. Results include weight gain, morphometry of the intestine, dissacharidases, total proteins, and nucleic acid in both TVLs and intestine in continuity. This model is inexpensive, easy to handle, and ideal for studying the effect of dietary factors on intestinal growth and maturation, separating the direct effect of diet on the intestine from systemic effects. PMID- 3351736 TI - Masturbation. PMID- 3351737 TI - More similar than different: children with chronic illness. PMID- 3351738 TI - Adolescent psychosocial adaptation to inflammatory bowel disease. PMID- 3351740 TI - Child health promotion practices. PMID- 3351739 TI - Enhancing patient compliance with health recommendations. PMID- 3351741 TI - Preterm infant stimulation: the analysis of a concept. PMID- 3351743 TI - Spiritual care. Helping a guilt-ridden patient. PMID- 3351742 TI - Health information needs of Medicaid enrollees and medically underinsured. PMID- 3351744 TI - You can be the friend who makes a difference. PMID- 3351745 TI - Spotlight: Korea. A Christian nurses' movement takes root. PMID- 3351746 TI - Can I assure a non-Christian patient of God's forgiveness? PMID- 3351748 TI - Measurement of intraocular lens decentration and tilt in vivo. AB - A method for measuring the tilt and decentration of intraocular lenses (IOLs) in the static eye using the Purkinje image locations is presented. The patient fixates on a target that is coaxial with the camera or is at a predetermined angle with the camera axis. A telecentric stop is introduced in the camera so the positions of the Purkinje images on the film are independent of their distance from the camera. Measurements of the image locations on the film are used with anterior chamber depth and corneal curvature measurement to calculate the tilt and decentration of the IOL. In a group of 14 randomly selected patients with posterior chamber IOLs, 13 gave Purkinje images that could be measured. The average tilt was 7.8 degrees and the average decentration was 0.7 mm. PMID- 3351747 TI - Four incision radial keratotomy. AB - Radial keratotomy is a constantly evolving procedure. This paper investigates the value of four incision radial keratotomy. The possible advantages of fewer incisions include increased corneal stability, lower risk of perforation, less potential of endothelial cell loss, decreased chance of overcorrection, and simplification of the procedure. We evaluated the results of four incision radial keratotomy in 55 eyes of 31 patients. Follow-up ranged from one to 18 months. Results in low myopia (-2.00 to -3.12 diopters) show 93% of the patients were 20/40 or better, 90% were within +/- 1 diopter of emmetropia, and no patients were overcorrected greater than 1 diopter. In moderate myopia (-3.25 to -4.37 diopters), 84% of the patients were 20/40 or better, 92% were within +/- 1 diopter of emmetropia, and no patients were overcorrected greater than 1 diopter. Regression analysis was performed and it was determined that the postoperative result was equal to .262 + [1.293 x preop spherical equivalent] - [1.166 x optical zone] + [0.56 x depth] + [.038 x age], R = .87. PMID- 3351749 TI - Comparison of the SRK II formula and other second generation formulas. AB - A simple modification of the SRK formula was developed for use with extreme axial length cases (short and long eyes) to maximize prediction accuracy in these groups. For "average" eyes (over 75% of all cases), SRK needed no modifications to maintain maximum predictive accuracy. The new, modified SRK formula (SRK II) was compared with current second generation formulas and the Binkhorst formula. The SRK II formula, while maintaining the simplicity and ease of the SRK, was comparable to and in some cases superior to the other formulas. Overall, 80.0% of 2,068 posterior chamber intraocular lenses from seven different manufacturers demonstrated less than one diopter of prediction error and only 0.5% had three or more diopters of error. In short eyes (less than 22 mm), 74.0% were corrected to within one diopter and less than 2.0% had three or more diopters of error. In long eyes (greater than or equal to 24.5 mm), 78.0% of cases demonstrated less than one diopter of error and less than 1.0% had three or more diopters of error. Although the SRK II formula is incorporated in most new A-scan units, the modifications are so simple that surgeons can take the standard SRK predictions and mentally calculate the modifications for extreme cases. PMID- 3351750 TI - A new technique of congenital cataract surgery with primary posterior chamber intraocular lens implantation. AB - We present a series of nine cases involving primary intraocular lens implantation in congenital cataracts. Because of the problems encountered with the technique used in the earlier cases, we developed a new surgical technique that may be described as primary epilenticular posterior chamber lens implantation followed by pars plana endocapsular lensectomy. This new technique ensures a clear pupillary area, minimizes postoperative complications, and ultimately prevents amblyopia, resulting in useful vision. PMID- 3351751 TI - Visual outcome of cataract extraction and lens implantation complicated by vitreous loss. AB - A retrospective study of 62 cases of planned extracapsular cataract extraction with intraocular lens implantation complicated by vitreous loss revealed a visual outcome of 20/20 to 20/40 in 34 eyes (54.8%), 20/50 to 20/80 in 16 eyes (25.8%), 20/100 to 20/400 in six eyes (9.7%), and worse than 20/400 in six eyes (9.7%). If preexisting ocular diseases such as glaucoma and macular degeneration are eliminated, 77.3% achieved a visual acuity of 20/40 or better. PMID- 3351752 TI - A short haptic diameter modified J-loop intraocular lens for improved capsular bag performance. AB - The laboratory and clinical characteristics of a modified J-loop intraocular lens (IOL) are presented. The lens features a 6 mm polymethylmethacrylate optic with uniplanar polypropylene loops of a 12 mm overall haptic diameter. The haptic design has a low resistance to compression at all diameters down to 9 mm. The relationship of the haptic configuration to the architecture of the capsular bag facilitates easy capsular bag implantation and consistent IOL centration in eyes with small and moderate capsular bag diameters. Three hundred fourteen lenses have been implanted over a one year period with no instance of asymmetric capsular bag-ciliary sulcus IOL placement, optic decentration, or pupillary capture. PMID- 3351753 TI - Wound healing following excimer laser radial keratotomy. AB - A pulsed excimer laser was used to produce radial keratotomy in vivo in human corneas and the wound healing process was studied. Fluences of 370 mJ/cm2 at a repetition rate of 20 Hz were effective and atraumatic. The wound healing process was remarkably uneventful without an inflammatory or immune reaction apparent at 21 days. Consistent flattening of the cornea was obtained by shallower cuts than with conventional radial keratotomy techniques. PMID- 3351754 TI - Neodymium:YAG laser phacofracture: an aid to phacoemulsification. AB - A series of approximately 1,000 cases of nucleus pretreatment prior to phacoemulsification is presented. Current results indicate that the technique eases phacoemulsification, especially of hard nuclei, and has little risk when done properly. PMID- 3351755 TI - An experimental model for uveal touch syndrome. AB - Posterior chamber intraocular lenses (IOLs) were implanted in cat eyes after extracapsular cataract extraction or phacoemulsification. Various degrees of iris and IOL contact occurred. In 52% of the eyes in which contact was present, there was associated fibrovascular membrane formation, which was statistically significant when compared to eyes in which there was no iris-IOL contact. The eyes were examined histopathologically; proliferation of anterior cuboidal cells, as well as a fibrous response within the stroma, was noted in eyes with the most extensive contact. Human clinical correlates are discussed. This study demonstrates experimentally that the iris will not tolerate significant prolonged IOL contact. PMID- 3351756 TI - Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part III: Giant cell formation on the implanted lens surface. AB - Among the cell components appearing on an implanted intraocular lens (IOL), the macrophage is the most active participant in the foreign-body response. The morphological stages of the macrophage in the response include not only an activated form and a flat epithelioid cell, but also a giant cell observed in the later stage of the response. The giant cells on the IOLs implanted in the rabbit eye and in the mouse peritoneal space were investigated by means of Wolter's implant cytology staining and scanning and transmission electron microscopic observation. Differences in the two biological environments as the site of IOL implantation are discussed. PMID- 3351757 TI - Clinical comparison of the SITE IRAS hand-held interferometer and Haag-Streit Lotmar visometer. AB - The preoperative testing of retinal acuity was evaluated using two instruments in each of 35 eyes having extracapsular cataract extraction. Retinal acuity was measured using the SITE IRAS hand-held interferometer and the Haag-Streit Lotmar visometer. The postoperative findings are given for comparisons of final acuity, prediction, and instrument evaluation. The results showed predicted acuity to be within two lines of the final acuity in 57.1% of eyes with the Haag-Streit unit and in 42.8% of eyes with the SITE instrument. The instrument differences were more in procedure than in results. PMID- 3351758 TI - Glare disability devices for cataractous eyes: a consumer's guide. AB - We evaluated five commercially available glare testers to determine how accurately each device predicted outdoor Snellen acuity in cataract patients. Predicted outdoor Snellen acuity was compared to actual Snellen outdoor acuity for the Miller-Nadler glare tester, the brightness acuity tester (BAT), the InnoMed true vision analyzer (TVA), the VisTech VCT 8000, and the EyeCon 5. All five devices were evaluated in a single series of eyes. We ranked the five glare testers as follows based upon their ability to predict outdoor Snellen acuity within one Snellen line: (1) BAT (73%), (2) TVA (69%), (3) VisTech VCT 8000 (56%), (4) Miller-Nadler (47%), and (5) EyeCon 5 (15%). All five devices were also evaluated for their capacity to provide false negative or false positive results and for testing time per eye, test difficulty level for the patient, versatility, upgrading capacity, examining room adaptability, and price. We concluded that glare testing of cataract patients is necessary to measure visual disability and that glare testing devices vary in their ability to predict outdoor vision. PMID- 3351760 TI - Synthetic cataract teaching system for phacoemulsification. AB - This paper describes a surgical training system for teaching and practicing the necessary skills to perform phacoemulsification, endocapsular phacoemulsification, and small incision intraocular lens insertion techniques. The surgical system includes head, bilateral globes, removable corneas, and replaceable synthetic cataracts of varying density. This synthetic system simulates ocular surgery more closely than previously used animal eyes and allows the surgeon to practice new techniques in laboratory courses and in the operating facility. PMID- 3351759 TI - Pulmonary edema following retrobulbar block. AB - We report a patient requiring keratoplasty who developed acute pulmonary edema following the administration of a retrobulbar block for anesthesia. A variety of factors that may have been implicated in the genesis of this complication are discussed. PMID- 3351761 TI - Lens implant exchanges for incorrect power: results of an informal survey. AB - Despite the introduction of ultrasonic axial length measurements and a variety of intraocular lens implant prediction formulas, postoperative predicted errors greater than 2 diopters occur in approximately 5% to 10% of lens implantations, and occasional errors of 5 diopters to 7 diopters or greater are still encountered. An informal survey revealed successful lens implant exchanges for initial postoperative refractive errors of +4.37 to -14.00 diopters in eight eyes. PMID- 3351762 TI - One consumer's experience with a phacoemulsification device. PMID- 3351763 TI - A consumer's suggestion. PMID- 3351764 TI - Envelope maneuver facilitated by a truly closed chamber technique. PMID- 3351765 TI - Radial keratotomy redux. PMID- 3351766 TI - The law and your profession. PMID- 3351767 TI - Your CE topic this month (No. 29). An update on natural and artificial sweeteners. PMID- 3351768 TI - A new life for my cancer patient. PMID- 3351769 TI - The disclosure of patient care errors by nurses: what duty is owed? PMID- 3351770 TI - Evaluating anemia in children. PMID- 3351771 TI - Your CE topic this month (No. 30). Update on pain therapy (Part 2). PMID- 3351772 TI - Recovering the ESWL patient. PMID- 3351773 TI - An ambulatory approach to ESWL. PMID- 3351774 TI - GU-PACU orientation. PMID- 3351775 TI - What do you look for in the pediatric postanesthesia patient? PMID- 3351776 TI - Practical points in the care of the post-ESWL patient. PMID- 3351777 TI - The rationale and benefits of a required preadmission ambulatory surgery program. PMID- 3351778 TI - CV or resume? PMID- 3351779 TI - Historical research: one step back...two steps forward. PMID- 3351780 TI - Hemodynamic waveform analysis. Part II. PMID- 3351781 TI - Desmopressin acetate. PMID- 3351782 TI - Maintaining CPAN status through recertification. PMID- 3351783 TI - Individual prepacemaker neurons can modulate the pacemaker cycle of the gymnotiform electric fish, Eigenmannia. AB - The prepacemaker nucleus (PPN) in the midbrain of the gymnotiform electric fish Eigenmannia provides the only known neuronal input to the medullary pacemaker nucleus, which triggers each electric organ discharge (EOD) cycle by a single command pulse. Electrical stimulation of the PPN elicited two distinct forms of modulations in the pacemaker activity, brief accelerations, hence referred to as 'chirps', and gradual frequency shifts with a time constant of approximately one second. The associated EOD modulations were indistinguishable from natural communication signals. Depending upon the site of stimulation, the two forms of modulation could be elicited alone or superimposed (Fig. 1). Stimulation sites eliciting only chirps could be separated from sites eliciting only gradual shifts by as little as 60 micron. The magnitude of the elicited chirps depended upon the timing of the pulse stimulus with reference to the phase of the pacemaker cycle (Figs. 2, 3). Extracellular and intracellular recordings of single PPN neurons revealed that an action potential from a single neuron generates a chirp, and that the magnitude of the chirp depends upon the timing of the action potential with reference to the phase of the pacemaker cycle (Figs. 4, 5). The spike activity of these neurons had no relation to the jamming avoidance response (JAR), suggesting independent neuronal mechanisms for chirps and the JAR. Depolarization of such neurons by current injection produced bursts of chirps (Fig. 6), and intracellular injection of Lucifer Yellow identified these cells as a large type of PPN neuron which could also be retrogradely labeled from the pacemaker with horseradish peroxidase (HRP) (Fig. 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351784 TI - Modification of spectral sensitivities by screening pigments in the compound eyes of twilight-active fireflies (Coleoptera: Lampyridae). AB - 1. ERG S(lambda) were determined in dark-adapted intact preparations of 6 North American firefly species (Photinus collustrans, marginellus, pyralis, macdermotti, scintillans and Bicellonycha wickershamorum) which restrict their flashing activity to twilight hours. The curves possess narrow (1/2 bandwidth = 50-60 nm) peaks in the yellow (560-580 nm) and a shoulder in the violet (370-420 nm), with a marked attenuation (1.4-2.2 log units) of sensitivity in the green (480-530 nm) region of the spectrum (Fig. 1). Two additional species (Photuris potomaca and frontalis) which initiate flashing at twilight and continue on late into the night (twi-night) possess broad sensitivity maxima around 560 nm (Fig. 3). 2. Selective adaptation experiments isolated near-UV and yellow in P. scintillans (Fig. 2). In the dorsal frontal region of the compound eyes in P. frontalis, high sensitivity existed only in the short wavelength region (near-UV and blue) with a maximum in the blue (lambda max 435 nm) (Fig. 4). 3. The in situ MSP absorption spectrum of the screening pigments was determined in preparations of firefly retina. a) Two kinds of dark brown granules were found in the clear zone region. These granules absorb all across the spectrum with a gradual increase in optical density in the shorter wavelength region in P. pyralis (Fig. 5). b) Besides dark granules, pink-to-red colored screening pigments were present in the vicinity of the rhabdoms. The absorption spectra of these pigments determined in five species were narrow (1/2 bandwidth = 50-80 nm) with species specific differences in their peak absorption in the green at 525 nm, 510 nm, 512 nm and 517 nm in P. scintillans, macdermotti, collustrans and pyralis, respectively (Fig. 6). A similar pigment was found in P. marginellus with a lambda max at 512 nm (Fig. 7). In all cases, transmission increased both at long and short wavelengths, but more sharply in the long wavelength region (Figs. 6 and 7). Hence each twilight-restricted species has its own unique colored screening pigment. A yellow pigment whose absorption spectrum differed from those found in genus Photinus was found in twi-night active Photuris potomaca (lambda max 461 nm) and night-active P. versicolor (lambda max 456 nm). The transmission of the Photuris pigment increased sharply only in the long wave-length region (Fig. 8).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3351785 TI - Phase response curves for social entrainment. AB - Phase shifts in free-running activity rhythms of male golden hamsters, Mesocricetus auratus, often occur when they establish a new territory and home after a cage change. Similar shifts also often occur after pairs of animals interact with each other for half an hour. When these events take place during the middle of the hamsters' subjective day, they produce phase advances: when late in the subjective night, they produce phase delays. Repeated social interactions at the same time of day can entrain activity rhythms in a way consistent with the shape of the phase response curves. Not all individuals become entrained, as is predictable from the modest amplitude of the phase response curve. The effects of social interactions and of other disturbances may be mediated through an oscillator phased by general arousal. The present findings have implications for the interpretation of drug-induced changes in biological rhythms. PMID- 3351786 TI - Voltage clamp characterization of a calcium-dependent chloride conductance in a putative invertebrate motoneuron. AB - 1. The properties of a Ca-activated Cl-current ICl(Ca) were investigated with the two electrode voltage clamp technique in the AL1 cell of the leech Haementeria ghilianii. 2. ICl(Ca) was revealed after Cl-loading of the cells, with outward K currents eliminated by replacement of intra- and extracellular K with Cs, and with Na currents blocked by 1 microM TTX. CsCl-containing electrodes were used for recording and current passing. 3. In response to depolarizing voltage steps the cells exhibited sustained Cl-dependent currents the size and polarity of which varied with [Cl]0. The reversal potentials of tail currents of this conductance varied with [Cl]0 as predicted for the equilibrium potential of Cl by the Nernst equation and were unaffected by changes in extracellular cation concentration. 4. The decay of the Cl-dependent tail-currents followed a process which could be described by the sum of two exponentials with time constants tau 1 and tau 2 on the order of about 100 ms and 800 ms, respectively. No voltage dependence of the time constants was apparent; however, tau 1 varied with the amount of Ca-influx. 5. The Cl-current required Ca for its activation. All current flow was abolished in Mn-containing Ringer solutions and when Ba was substituted for Ca. However, Sr could partially substitute for Ca as an activator of the current. 6. The activation curve for Cl-dependent tail currents was U shaped directly paralleling the amount of Ca-influx, and no Cl-current flow could be induced a depolarizations below the activation threshold or beyond the apparent reversal potential for the Ca-current.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351787 TI - Circadian oscillation of the multiple unit activity in the guinea pig suprachiasmatic nucleus. AB - In the guinea pig with chronically implanted electrodes, neuronal multiple unit activity (MUA) was recorded inside and outside the suprachiasmatic nucleus (SCN). Long-term recording of the SCN indicated distinct daily rhythms with a daytime peak in MUA during a 24-h light-dark (LD 12:12) cycle. On the other hand, MUA recorded from adjacent hypothalamic regions outside the SCN showed a phase reversal with a nighttime peak, similarly to the rat. The amplitude of the rhythms recorded outside the SCN was much smaller (one-half to one-quarter) than that inside the SCN. These rhythms persisted during constant darkness indicating characteristics of endogenous circadian rhythmicity. When the external light-dark cycle was delayed abruptly for 12 h, MUA rhythms showed a gradual phase shift taking 7-10 days for complete reentrainment. Overt behavior including sleep wakefulness did not show significant and consistent daily or circadian rhythms in spite of the distinct oscillation in neuronal activity inside the SCN. PMID- 3351788 TI - Characterization of circadian function in Djungarian hamsters insensitive to short day photoperiod. AB - Djungarian hamsters (Phodopus sungorus sungorus) depend mainly on day length to cue seasonal adjustments. However, not all individuals respond to short day conditions. A previous study from this laboratory proposed that nonresponsiveness to short day conditions rests with a defect in the circadian organization of these hamsters. In this study we found pronounced differences between responsive and nonresponsive hamsters in the expression of circadian rhythmicity under constant darkness and under constant illumination. While responsive hamsters showed a free-running activity pattern with a period of 23.86 +/- 0.04 h and responded to brief light pulses with the expected phase delays and phase advances, nonresponsive hamsters exhibited a period of 24.04 +/- 0.05 h and responded to light pulses with phase advances. Furthermore, 9 out of 15 responsive hamsters showed a clear split in the activity pattern within 8 weeks under constant light (80-100 lux), while only 1 of the 7 nonresponsive hamsters exhibited a split activity pattern. As a result of these differences in circadian function, nonresponsive Djungarian hamsters are incapable of proper photoperiod time measurement and photoperiod-induced seasonality. PMID- 3351789 TI - Neural control of ventilation in the shore crab, Carcinus maenas. II. Frequency modulating interneurons. AB - 1. We have identified a class of nonspiking interneurons which can control the frequency of ventilation in a graded manner. These frequency modulating interneurons (FMis) also receive synaptic inputs in-phase with the ventilatory motor output providing a functional positive feedback loop in the ventilatory system. The class of FMis is composed of three morphologically and physiologically distinct interneurons, FMi1, FMi2 and FMi3. 2. Depolarization of FMi1 increases the rate of ventilation, while hyperpolarization decreases the rate (Fig. 1). This control is restricted to a single ventilatory central pattern generator (CPG), (Fig. 2), although FMi1 sends processes into the neuropils of both hemiganglionic CPGs (Fig. 3). 3. Hyperpolarization of FMi2 increases the rate of both ventilatory CPGs while depolarization of this cell slows and eventually arrests the rhythm (Figs. 5 and 6). FMi2 receives a synaptic input correlated with the motor output of each of the ventilatory CPGs (Fig. 4). During periods of reversed ventilation, this cell is abruptly hyperpolarized and continues to be driven in-phase with the ventilatory motor output (Fig. 7). 4. Hyperpolarization of FMi3 increases the rate of ventilation and depolarization decreases the rate of ventilation produced by both CPGs (Fig. 10). This control of the ventilatory rate by FMi3 is graded (Fig. 11). There is no apparent change in the membrane potential of FMi3 during reversed ventilation and it is morphologically distinct from FMi2. 5. FMi2 and FMi3 may be involved in the switch in ventilatory motor pattern from forward to reversed ventilation. Hyperpolarization of FMi2 and depolarization of FMi3 can elicit bouts of reversed ventilation from both CPGs (Fig. 13). 6. These results suggest that the FM interneurons act in parallel to control the frequency of ventilation and may act as integrating elements between spiking 'command' fibers in the circumesophageal connectives and the nonspiking interneurons of the ventilatory CPG. PMID- 3351790 TI - Selectivity for harmonic structure in complex sounds by the green treefrog (Hyla cinerea). AB - 1. A psychophysical technique based on reflex modification was used to study the detection of two-tone complexes in background noise by the green treefrog (Hyla cinerea). Three different two-tone complexes were synthesized and presented to measure detection thresholds--a harmonic complex of 900 + 3000 Hz (periodicity of 300 Hz, mimicking the structure of the natural advertisement call); an inharmonic complex of 830 + 3100 Hz; and a second harmonic complex of 828 + 2760 Hz (periodicity of 276 Hz). 2. Masked thresholds and 'critical ratios' (signal-to noise ratios at threshold) were lowest for the two harmonic complexes (900 + 3000 Hz, mean 'critical ratio' of 16 dB; 828 + 2760 Hz, mean 'critical ratio' of 14 dB). For the inharmonic complex, for which there is no stable first-harmonic periodicity, the mean 'critical ratio' was 24 dB. These data suggest that the green treefrog is sensitive to the harmonic structure of complex sounds as a specific acoustic feature. 3. Because of the unique structure of the treefrog's inner ear, the heightened behavioral sensitivity to harmonic complexes must be due to processing in the central, rather than peripheral, auditory system. PMID- 3351791 TI - Is the Army Hearing Conservation Programme working in the Territorial Army? AB - This was a clinical and audiometric survey of a sample of 299 Territorial Army (TA) servicemen in the London area to identify the priority to be given to and the broad content of a Hearing Conservation Programme for the TA. A questionnaire was used to estimate previous noise exposure and the use of hearing protection. It is estimated that 4% of TA personnel have a hitherto undetected hearing loss which would result in their medical downgrading. Noise is likely to be responsible for three-quarters of such cases. For 86% of the sample TA service is the major source of hazardous noise. There is strong tendency for hearing loss to increase with length of TA service although it is not possible completely to disentangle the effects of age and social exposure. PMID- 3351792 TI - The major causes of death in the Army and comparisons with the civilian population. AB - Statistics of 881 British Army male non-operational deaths between 1980 and 1984 were analysed and comparisons made with civilian mortality for certain categories of deaths. Disease accounted for 32% and injury for 68% of the deaths. Road traffic accidents (RTAs) comprised 40% and ischaemic heart disease (IHD) 13% of the total. The overall Standardised Mortality Ratio (SMR) was 92. By comparison with the UK civil population serving members of the Regular Army suffered considerably less from disease deaths (SMR 58) with the exception of IHD (SMR 92), but more from injury deaths (SMR 135). RTA deaths had an SMR of 200. The review suggests that attention should be directed towards incidents causing RTAs and drowning. Action taken in peace may have relevance to survival on operations. PMID- 3351793 TI - Ventilatory effects of isoflurane: a comparison with halothane in a draw-over system. AB - Halothane and isoflurane were studied using a draw-over anaesthetic system in two groups each of 25 patients to compare the ventilatory effects of the two agents in field anaesthesia. Respiratory variables were measured and it was confirmed that isoflurane is a more potent respiratory depressant than halothane, but satisfactory anaesthesia for short procedures was possible. PMID- 3351794 TI - Vulvar intra-epithelial neoplasia associated with other genital tract neoplasia. Four case reports and discussion. AB - It is recognised that a significant number of patients who develop vulvar intra epithelial neoplasia (VIN), will have had previous genital tract neoplasia. This has resulted in speculation that there may be a common aetiology and, in particular, on the possibility of an infective element. Four such cases from the Vulva Clinic at the Western Infirmary, Glasgow are presented for discussion. PMID- 3351795 TI - Do we need to know the ABO blood group in antenatal patients? AB - The importance of determination of ABO Blood Groups in antenatal patients is considered, particularly in the context of the diagnosis of ABO mediated haemolytic disease of the newborn and blood transfusion during pregnancy and delivery. It is concluded that the investigation is of little benefit to either patient or doctor, and that it should be abandoned as part of routine antenatal procedures. PMID- 3351796 TI - An after life. PMID- 3351797 TI - Cervical cytology screening in the Army. PMID- 3351798 TI - Ethnic variations in birth weight--a study of British, Chinese and Ghurkha babies. PMID- 3351799 TI - Pensions. PMID- 3351800 TI - British Military Hospital Dharan: surgical experience 1985-86. AB - The clinical experience of an army surgeon in a military hospital in East Nepal is discussed. The truly general nature of the work load is highlighted and the need for a broad based general training in surgery for such a task is well illustrated. A high degree of interdisciplinary cooperation was experienced and was indeed essential for good clinical practice. The health problems of a developing country are glimpsed. The severe limitations imposed on clinical practice as a consequence of limited facilities are particularly noteworthy. PMID- 3351801 TI - Saccharin and aspartame. Are they safe to consume during pregnancy? AB - Saccharin and aspartame are commonly used artificial sweeteners. Some of the currently available information on their safety in pregnancy was reviewed, with recommendations formulated on their use in the periconceptional period and pregnancy. PMID- 3351802 TI - Mental and physical effects of being a gynecologic teaching associate. AB - Over 90% of medical schools in the United States and Canada use gynecologic teaching associate (GTA) programs to instruct medical students in breast and pelvic examinations. Concerns about possible deleterious emotional, psychosocial or physical effects of such teaching activities upon the GTAs were evaluated. No sustained deleterious mental or physical effects of working as a GTA were found, supporting the continued use of the GTA instructional methodology. PMID- 3351803 TI - Adverse outcomes of pregnancy in women exposed to diethylstilbestrol in utero. AB - We analyzed data collected by interview and medical record review for 200 women exposed to diethylstilbestrol (DES) and 12,240 unexposed women to evaluate the relation between maternal DES exposure and outcomes of pregnancy. Low birth weight, short gestation, bleeding in the first trimester, toxemia, breech presentation and premature rupture of the membranes occurred more often among the exposed women. These relationships remained statistically significant after the use of linear regression and logistic regression analyses to control for multiple confounding factors. Both exposed women and their physicians should be aware of the possible relationship between maternal exposure to DES and late adverse outcomes of pregnancy. Close medical supervision of these women throughout pregnancy and delivery is recommended. PMID- 3351804 TI - Sexually transmitted diseases and the risk of tubal pregnancy. AB - Women who were hospitalized for tubal pregnancy in five hospitals in King County, Washington, between 1975 and 1979 were interviewed regarding a prior history of gonorrhea, genital herpes, genital warts and trichomoniasis. Their responses were compared to those of women who delivered a live-born child during the same period. Multiple logistic regression was used to control for the effects of race, gravidity, smoking, Dalkon Shield use, douching, number of sexual partners and history of additional sexually transmitted diseases. The risk of tubal pregnancy in women who reported a history of gonorrhea, relative to that in other women, was 5.1. As compared to controls, women with tubal pregnancy more often reported a history of genital herpes and a history of trichomoniasis. PMID- 3351805 TI - Bacillus Calmette-Guerin immunotherapy in ovarian cancer. AB - Forty-six advanced ovarian cancer patients treated with conventional modalities with the addition of bacillus Calmette-Guerin (BCG) immunotherapy showed prolonged survival when compared to controls not given BCG. Although the data suggest enhancement of survival with the addition of BCG to conventional treatment, the fact remains that disease recurrence ultimately claims the lives of most of these patients. Nonetheless, patients are surviving longer in the face of advanced disease. PMID- 3351806 TI - The Papanicolaou smear and the cervigram. A preliminary report. AB - We reviewed the results of Papanicolaou smears and cervigrams obtained at the same session from 250 patients. Seven Papanicolaou smears were abnormal, and 56 cervigrams were abnormal. Fourteen cases of cervical intraepithelial neoplasia I and two cases of cervical intraepithelial neoplasia III were missed by the Papanicolaou smear but identified by cervicography. PMID- 3351807 TI - Maternal risk status and postdate pregnancy outcome. AB - Using a 1982-1985 regional perinatal network data base of 69,746 infants, a retrospective study was conducted to compare the perinatal outcome of 7,729 postdate infants (greater than or equal to 42 weeks' gestation) by maternal risk status. Due to additional antenatal complications, of which 8.0% were hypertension and/or diabetes, 48.4% of the postdate pregnancies were classified as at risk. As expected, high-risk women experienced a higher incidence of adverse perinatal outcomes than did low-risk women. The incidence of meconium staining, low five-minute Apgar scores and perinatal mortality increased beyond term and was found most commonly in infants from high-risk pregnancies, especially those involving hypertension and diabetes mellitus. These results suggest that high-risk pregnancies probably should not enter the postdate period since their doing so places the infant at serious risk. PMID- 3351808 TI - Problem visits to a family planning clinic. AB - In order to obtain information necessary for optimum delivery of services, data were collected on the nature of the services provided at a family planing clinic. Clinic visits were divided into initial, annual, routine, problem, supply, educational and unknown. An analysis of the "problem" visits was undertaken to assess various epidemiologic aspects of such visits and to identify areas of clinic efficiency that could be improved. Problem visits were defined as any visits for which the patient had a presenting complaint. Age, level of education, method of contraception and parity were statistically associated with problem visits. When compared to Pill users, diaphragm users, intrauterine device users and non-users had a higher-than-expected number of problem visits. Less educated women and teenagers had a lower-than-expected number of problem visits when compared to more educated and older women. Socioeconomic status and problem visits were not statistically associated. Problem visits required more time, utilized more medical services and resulted in more referrals to the gynecology clinic than did other visit types. As a result of this analysis, we have increased our educational efforts for patients at high risk of problem visits and have instituted a special problem-oriented family planning clinic in which a full complement of house staff and ancillary personnel are available. This arrangement makes the uncomplicated family planning clinic run more smoothly and efficiently and obviates the need for time-consuming and cost-ineffective referrals. PMID- 3351809 TI - An unusual intrapartum fetal heart rate pattern. A case report. AB - An unusual fetal heart rate pattern was detected intrapartum in a patient with an otherwise uncomplicated pregnancy. An approach to the evaluation of the unusual fetal heart rate pattern was developed. PMID- 3351810 TI - Questionable role of amniocentesis in the etiology of amniotic band formation. A case report. AB - A preterm infant had an amniotic band sequence. Anomalies included left leg amputation and digital anomalies of the hands. The umbilical cord was short, and histologic sections of the placenta demonstrated partial avulsion of the amnion and fibrosis of the underlying chorion. Ultrasound at 21 weeks was normal, there was no history of trauma during the pregnancy, and no amniocentesis had been performed. Despite isolated case reports of amniotic band sequence associated with amniocentesis, we doubt that amniotic band formation is a significant risk after second-trimester amniocentesis. PMID- 3351811 TI - An evaluation of the clinical staging of endometrial cancer. AB - Therapeutic approaches to endometrial cancer have traditionally been based on preoperative clinical staging. We conducted a retrospective review of 56 women with diagnoses of stage I and II endometrial cancer in order to compare preoperative clinical staging with postoperative staging based on pathologic data. We found a change in stage based on surgical findings in 41.1% of the cases. Endocervical curettage was falsely positive in 92.8% of cases. In addition, an overall change in tumor grade occurred in 39.3% of patients. Preoperative clinical staging of endometrial cancer is associated with a large margin of error when compared to surgical pathologic data. PMID- 3351812 TI - Orchitis after a rubella vaccination. A case report. AB - Mild orchitis developed after a rubella vaccination. This is the first case report documenting such an event, and it illustrates how viral orchitis may affect sperm counts and motility. PMID- 3351813 TI - Six independent neoplasms in one woman. A case report. AB - A woman had six independent neoplasms. In reviewing the world literature, no case report was found of a patient with carcinomas of the skin, cecum, kidney, ovaries (bilateral, independent and synchronous) and endometrium. PMID- 3351814 TI - Hysterectomy and prior incontinence surgery as risk factors for failed retropubic cystourethropexy. AB - The effects of prior hysterectomy and incontinence surgery were evaluated retrospectively in 86 women undergoing modified Burch cystourethropexy. These women were evaluated before and three months after surgery with multichannel urodynamic testing. Forty percent of the 50 women with prior incontinence surgery remained incontinent after the cystourethropexy even though 94% of them had undergone anatomic correction. This result was not statistically different from the 28% failure rate in patients without prior incontinence surgery. Forty-two percent of the 62 women who had previously undergone hysterectomy failed cystourethropexy despite anatomic correction in 95%. This finding was significantly different from the 17% failure rate in women without prior hysterectomy (P less than .025). This retrospective analysis suggests that prior hysterectomy may place women at increased risk of continued incontinence following cystourethropexy despite anatomic correction of urethrovesical junction descent. Contrary to the results of other investigators, women with prior incontinence surgery in this study were not found to be at significantly greater risk of incontinence after cystourethropexy. PMID- 3351816 TI - CO2 laser myomectomy in an infertile population. AB - Thirty-two infertility patients with uterine myomas underwent laser myomectomy with the CO2 laser. Twenty-four patients (75%) had persistent primary infertility, with 8 (25%) experiencing recurrent abortions. Twenty (63%) of the 32 conceived (14/24 [58%] with primary infertility and 6/8 [75%] with secondary infertility); 17 (59%) ultimately had a viable term pregnancy. The mean interval from surgery to pregnancy was 8.5 months. The risk factors of age, duration of infertility, size and number of fibroids, and menorrhagia did not appear to influence the success rate or increase the complication rate. The advantages of the CO2 laser for myoma surgery are decreased adhesion formation, improved hemostasis, precision of application and improved reproductive performance. PMID- 3351815 TI - Efficacy of danazol treatment for minimal endometriosis in infertile women. A prospective, randomized study. AB - We compared pregnancy rates between a danazol-treated and an untreated group of infertile women with minimal endometriosis. After completion of a basic infertility workup and laparoscopy, women with minimal endometriosis were entered into the study and randomly selected to receive either a six-month course of danazol or no treatment at all. Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be noncontributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12-month period that started immediately after laparoscopy in the untreated group and after completion of danazol therapy in the treated group. The cumulative pregnancy rate (+/- SEM) was 37.2 +/- 8.4% in the danazol group (n = 37) and 57.4 +/- 10.4% in the untreated group (n = 36) (NS, P greater than .10). This prospective, randomized study showed danazol to be ineffective in improving pregnancy rates over doing nothing at all in patients with minimal endometriosis. PMID- 3351817 TI - Hyperferritinemia in ovarian cancer. AB - A prospective study was conducted on 50 women with ovarian cancer to determine the association of elevated serum ferritin and ovarian cancer and its potential as a tumor marker. The controls consisted of 116 healthy volunteers, 51 patients with benign gynecologic tumors and 15 patients with benign liver disease. The mean ferritin level in patients with ovarian cancer was 436.7 ng/mL, significantly higher than that in the controls. The effect of chronology on the serum ferritin was also investigated. Hyperferritinemia was observed in 25 (50.0%) of 50 patients with ovarian carcinoma. In patients with liver metastases a marked increase in ferritin was noted. The rate of ferritin elevation in patients with epithelial carcinoma and no hepatic involvement was 21.4%. PMID- 3351818 TI - Incidence of Chlamydia trachomatis in peripartum fallopian tubes. AB - We investigated the presence of Chlamydia trachomatis in fallopian tubes of patients undergoing Pomeroy tubal ligation in the immediate postpartum period with culture on cycloheximide-pretreated McCoy cells and with immunofluorescence staining. Two of 20 women were culture positive in both tubes, representing 10% culture positivity. Both patients were multiparous and black and reported no previous history of either pelvic inflammatory or sexually transmitted disease. Neither developed intrapartum or postpartum fever or any other signs of infection. These findings indicate that C trachomatis can be present in tubes of symptom-free pregnant women and not cause infectious morbidity either prepartum, intrapartum or postpartum. PMID- 3351819 TI - Skin preparation methods before cesarean section. A comparative study. AB - Preoperative skin preparation before cesarean section using a one-minute alcohol wash followed by application of an iodophor-impregnated adhesive film was evaluated in a prospective, randomized, controlled study of 79 patients. The iodophor film was as effective as the five-minute iodophor scrub followed by an iodophor wash, as determined by a reduction in skin bacterial counts. Clinical infectious morbidity was no different between the treatment and control groups, although the study was too small to draw statistically significant conclusions in this respect. This study demonstrated the antimicrobial effectiveness of a new, more rapid method of pre-operative skin preparation before cesarean section as compared to a longer, traditional method. This new, rapid method offers advantages for many patients undergoing abdominal delivery. PMID- 3351820 TI - Pregnancy outcome at greater than or equal to 20 weeks' gestation in women in their 40s. A case-control study. AB - The obstetric performance of 166 women in their 40s who delivered during a one year period at greater than or equal to 20 weeks' gestation was compared to that of a cohort of controls younger than 40. Medical complications--diabetes, chronic hypertension and antepartum bleeding--occurred more frequently in the older patients. They had a threefold increase in antepartum hospital admissions over the controls (23.5% vs. 7.8%). Both groups had the same perinatal mortality rate, 18/1,000, and their newborns had similar incidences of neonatal complications except for a higher frequency of major and minor congenital anomalies in the study group (16% vs. 8.4%). The older patients had a longer second stage of labor. Older nulliparas had a higher incidence of premature deliveries and cesarean sections than did their controls. The outcome of pregnancy in this age group is affected by multiple confounding variables; medical complications, parity and age play major roles. PMID- 3351821 TI - Results of 317 contraction stress tests with controlled nipple stimulation using an electric breast pump. AB - Nipple stimulation is widely used for producing uterine contractions. High rates of hyperstimulation have been reported with various manual methods of stimulation. A study was undertaken in an effort to standardize the mode and amount of stimulation. Three hundred seventeen contraction stress tests were done using an automatic electric breast pump with precise pressure control. This method was successful in achieving adequate contractions in 84.2%. Hyperstimulation of the uterus was encountered in 4.1% of all tests performed. Side effects and complications were minimal. PMID- 3351822 TI - Fetal acoustic stimulation testing. III. Predictive value of a reactive test. AB - The nonstress test (NST) is a helpful adjunct to the management of high-risk pregnancies. However, fetal sleep states may lead to falsely nonreactive tests. We assessed the usefulness of transabdominal acoustic stimulation of the fetus and demonstrated an approximately 50% reduction in the number of nonreactive tests and a shorter testing time. No change in the predictive reliability of a reactive test was observed. With regard to the intrapartum and neonatal outcome in women delivering within seven days of a reactive test, no difference between the incidence of meconium-stained amniotic fluid, depressed one- or five-minute Apgar scores or operative intervention for fetal distress could be identified. A reactive test evoked by acoustic stimulation is as reliable as the NST. It offers the additional benefits of reduced testing time and a lower incidence of nonreactive tests. PMID- 3351823 TI - A comparison of cefonicid and cefoxitin for preventing infections after vaginal hysterectomy. AB - One hundred women who underwent vaginal hysterectomy were randomly and prospectively divided into two study groups, one to receive a single, 1-g preoperative dose of cefonicid and the other to receive 2 g of cefoxitin preoperatively and postoperatively for a total of four doses. There were no differences between the two groups in the rates of febrile morbidity, urinary tract infection, serious infection, noninfectious morbidity or duration of hospitalization. Both cefonicid and cefoxitin were equally effective in preventing postoperative infectious morbidity and demonstrated little difference in side effects. The single-dose regimen of cefonicid provides the advantages of decreased cost and prolonged therapeutic tissue levels when compared to cefoxitin. Perioperative antimicrobial prophylaxis with this single-dose cephalosporin provides a cost-effective regimen that is both safe and prophylactically effective. PMID- 3351824 TI - Cervical pregnancy managed by placement of a Shirodkar cerclage before evacuation. A case report. AB - Cervical pregnancy can be managed by cervical cerclage placement before evacuation. Prophylactic cerclage placement in the first trimester of cervical pregnancy may obviate further intervention to control bleeding. PMID- 3351825 TI - Erythema multiforme in a pregnancy resulting from in vitro fertilization. A case report. AB - Erythema multiforme minor occurred in a woman whose pregnancy, resulted from in vitro fertilization. The skin lesions appeared at 12 weeks of gestation, while the patient was receiving injections of progesterone in oil. She was treated with prednisone and had a benign disease course and an uneventful pregnancy and delivery. PMID- 3351826 TI - Spontaneous adrenal hemorrhage in pregnancy. A case report. AB - Spontaneous adrenal hemorrhage is rare during pregnancy. Most reported cases have been associated with preeclampsia-eclampsia, trauma or septicemia. A woman was treated for recurrent unilateral adrenal hemorrhage during pregnancy. PMID- 3351827 TI - Distal segment tubal pregnancy after segmental resection for an isthmic pregnancy. A case report. AB - The second case occurred of pregnancy in the remaining distal segment of a fallopian tube after segmental resection for an isthmic pregnancy. PMID- 3351828 TI - Noncardiogenic pulmonary edema as a rare complication of blood transfusions. A case report. AB - A woman was treated for leukoagglutinin-induced noncardiogenic pulmonary edema resulting from a blood transfusion. PMID- 3351829 TI - Leiomyoma in a mullerian remnant. A case report. AB - Leiomyomas are a rather common occurrence in the normal uterus. Mullerian dysgenesis, however, occurs in only approximately 1 in 5,000 female births. We found no case reports of leiomyoma arising from a mullerian remnant, as in the case reported here. Surgical management considerations include identification of the blood supply, separation of the mass from the broad ligament and care in identifying the entire length of the ureter. Due to the extreme rarity of leiomyoma in mullerian remnants, it should be considered low on the list of differential diagnoses of pelvic masses in women with mullerian dysgenesis. PMID- 3351831 TI - Etiopathogenesis of rheumatoid arthritis-like disease in MRL/1 mice: II. Ultrastructural basis of joint destruction. AB - MRL/1 mice develop a spontaneous hindlimb arthropathy characterized by proliferation of synovial cells and by dissociation between early destruction of articular tissue and the presence of inflammatory cell infiltration. To characterize the ultrastructural details of the synovial cells of these mice, knee joints from MRL/1, MRL/n, and BALB/c mice were examined by light and electron microscopy. Since the proliferating synovial cells of MRL/1 mice resemble the previously described proliferative synovial cells seen in histopathologic specimens from early rheumatoid arthritis, further study of these cells may provide new insights into the pathogenesis of early joint tissue destruction in human rheumatic disease. PMID- 3351830 TI - Immunogenetics of rheumatoid arthritis. PMID- 3351832 TI - Reflex sympathetic dystrophy syndrome coincident with acute diabetic neuropathy. AB - Diabetes mellitus and peripheral neuropathies are considered to be unusual causes of the reflex sympathetic dystrophy syndrome. Their coexistence in a patient with this syndrome is rare and considered to be incidental. We report a case in which remission of the syndrome accompanied the resolution of the diabetic neuropathy. A possible pathophysiologic mechanism connecting these conditions is discussed. PMID- 3351833 TI - Universal spondylodiscitis in a patient with erosive peripheral arthritis and apatite crystal deposition. AB - A patient with erosive peripheral arthritis in whom vasculitis and monoclonal IgG kappa paraprotein were associated with sacroiliitis and widespread destruction of intervertebral discs is reported. Crystals resembling apatite were identified in intervertebral disc material, and we postulate that the discitis was accelerated by apatite deposition. Our case illustrates a unique example of axial involvement in rapidly progressive joint disease. PMID- 3351834 TI - Should pain as a presentation of non-Hodgkin lymphoma invading muscle. AB - Non-Hodgkin lymphoma commonly presents with extranodal disease, but rarely involves connective tissue and muscle. When present, muscle involvement is usually in the leg. We describe a case of non-Hodgkin lymphoma with muscle invasion presenting as shoulder pain. PMID- 3351835 TI - Fetal wastage in patients with rheumatoid arthritis. PMID- 3351836 TI - Parental mortality and rheumatoid arthritis. PMID- 3351837 TI - Abdominal aortic aneurysm mimicking hip disease. PMID- 3351838 TI - Asymptomatic sacroiliitis in systemic lupus erythematosus. PMID- 3351839 TI - The erosive front: a topographic study of the junction between the pannus and the subchondral plate in the macerated rheumatoid metacarpal head. AB - The junction between cellular pannus and cartilage/bone was identified grossly on rheumatoid metacarpal heads. Its topography was displayed by scanning electron microscopy using macerated samples. A uniform pattern of resorption bays, typical of osteoclastic activity, was seen spreading over the surfaces of both calcified cartilage and subchondral bone. The contact area between pannus and cartilage/bone was found to represent an erosive front. Morphologic evidence suggested that osteoclasts were primarily responsible for the destructive process. PMID- 3351841 TI - Anticardiolipin antibodies: smoking gun or smoke screen? PMID- 3351840 TI - Effects of rifampicin with and without isoniazid in rheumatoid arthritis. AB - A patient with rheumatoid arthritis (RA) experienced great improvement in her RA when given antituberculous treatment for pulmonary tuberculosis (TB). Two of the drugs used in TB, rifampicin and isoniazid, include immunomodulatory effects among their properties. To investigate whether these drugs have any effect in RA, we studied 20 patients who were given either rifampicin 600 mg daily (10 patients) or rifampicin 600 mg with isoniazid 300 mg daily (10 patients). Eighteen patients completed at least 3 months' treatment. Six of the 7 patients with early RA (less than 3 years) improved; their median erythrocyte sedimentation rate fell from 43.5-10 mm/h (p = 0.036) and median serum C-reactive protein from 40-0 mg/l (p = 0.036). Eleven patients with longer histories of RA did not improve. Our results suggest rifampicin with or without isoniazid may be effective in RA. PMID- 3351843 TI - Antiphospholipid antibodies in systemic lupus erythematosus: evidence of an association with positive Coombs' and hypocomplementemia. AB - Anticardiolipin antibodies (aCL) were evaluated in 65 consecutive patients with systemic lupus erythematosus using an enzyme linked immunoassay (ELISA) and were detected in 14 (22%). There was no association of aCL with active disease, specific clinical manifestations, high DNA binding or circulating immune complex levels. The presence of aCL was associated with lupus anticoagulant activity (p less than 0.001), positive VDRL (p less than 0.05), and lower mean platelet counts (p less than 0.05) and C3 levels (p less than 0.05). Both aCL and lupus anticoagulant activity were associated with positive Coombs' (p less than 0.01) and low C4 (p less than 0.01 and p less than 0.05, respectively). Analysis of red blood cell (RBC) eluates and absorption studies using fixed RBC suggested that some aCL may act as anti-RBC antibodies, likely directed at membrane phospholipid epitopes. Furthermore, we hypothesize that complement may participate as a cofactor maximizing lupus anticoagulant activity. PMID- 3351842 TI - Studies of IgG, IgM and IgA antiphospholipid antibody isotypes in systemic lupus erythematosus. AB - We evaluated the clinical relevance of 6 antiphospholipid antibodies including cardiolipin and their IgG, IgM and IgA isotypes in 92 patients with systemic lupus erythematosus (SLE). Antiphospholipid antibodies generally had significant associations with thrombocytopenia and a history of false-positive syphilis serologies. In 4 of 6 antiphospholipid antibodies, an inverse association with renal disease was observed. Antiphospholipid antibodies may moderate or protect against renal disease, or this may reflect the high doses of corticosteroids and cytotoxic drugs received by this group. Further studies are needed to determine how many antibody families cause these activities and to elucidate whether certain SLE subgroups possess differing specificities for each of the phospholipids. PMID- 3351844 TI - Enzyme linked (ELISA) immunoabsorbent assay for the detection of hidden 19S IgM rheumatoid factors in juvenile rheumatoid arthritis. AB - Determination of hidden IgM rheumatoid factors (RF) in juvenile rheumatoid arthritis (JRA) offers advantages for diagnosis and in following disease activity. Sera from 30 patients with JRA were assayed for RF by latex fixation test (LFT), sensitized sheep cell agglutination test (SCAT), nephelometry, and by ELISA. IgM containing fractions were prepared by chromatography and assayed for hidden RF by the hemolytic method and ELISA. Ten patients were seropositive by LFT. All of them gave positive tests on the serum for RF with the SCAT, nephelometry, and ELISA, and on the IgM containing fractions by the hemolytic assay and ELISA. Seventeen patients seronegative by LFT were positive for hidden RF by the hemolytic test and ELISA on the IgM containing fraction. When unfractionated serum was used, 15 were positive by ELISA. Three patients were seronegative and also negative for hidden RF by the hemolytic assay and ELISA. Thus, only 2 of 30 patients had discordant results between the hemolytic assay on the IgM containing fraction and the ELISA on the serum. Our results indicate the ELISA on the serum in conjunction with the LFT offers a simple, rapid, alternative test for hidden 19S IgM RF in JRA patients. PMID- 3351846 TI - Potential antitumor agents. 54. Chromophore requirements for in vivo antitumor activity among the general class of linear tricyclic carboxamides. AB - Structure-antitumor activity relationships are reported for a number of different examples (acridine, phenazine, anthracene, acridone, xanthenone, thioxanthenone, anthraquinone, pyridoquinazoline, dibenzodioxin, thianthrene, phenothiazine, phenoxazine, dibenzofuran, carbazole, and pyridoindole) of the general class of N [2-(dimethylamino)ethyl] linear tricyclic carboxamides. Only the compounds containing coplanar chromophores intercalated DNA. There is an absolute requirement for an oxygen or aromatic nitrogen (possibly as hydrogen-bond acceptors) peri to the carboxamide, together with a planar ring geometry for biological activity. In addition to further delineating the nature of the pharmacophore for this class of compounds, the work has also identified dibenzo[1,4]dioxin as a novel DNA-intercalating chromophore with in vivo antitumor activity. PMID- 3351845 TI - Beta-substituted phenethylamines as high-affinity mechanism-based inhibitors of dopamine beta-hydroxylase. PMID- 3351847 TI - Synthesis and copper-dependent antimycoplasmal activity of 1-amino-3-(2 pyridyl)isoquinoline derivatives. 1. Amides. AB - In order to investigate the antimycoplasmal activity of compounds structurally related to 2,2'-bipyridyl, a series of both aliphatic and aromatic amides derived from 1-amino-3-(2-pyridyl)isoquinoline were synthesized. The most active compounds appeared to be as active as Tylosin, an antimycoplasmal therapeutic that is used in veterinary practice, in the presence of a small nontoxic amount of copper. Furthermore, it was found that antimycoplasmal activity depends on the hydrophobic fragmental value of amide residue. A quantitative structure-activity relationship established the optimal hydrophobic fragmental value of the amide residue to be 0.30. PMID- 3351848 TI - Bile acids with a cyclopropyl-containing side chain. 3. Separation, identification, and properties of all four stereoisomers of 3 alpha,7 beta dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid. AB - 3 alpha,7 beta-Dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid (CUDCA) (2a), a side-chain cyclopropylog of ursodeoxycholic acid (UDCA) was shown to be a mixture of four stereoisomers (CUDCA A-D). The 22S,23R, and 22R,23S diastereoisomers have been separated, their respective configurations assigned by 13C NMR spectroscopy, and original synthetic schemes for their preparation elaborated. Moreover, theoretical models of the structure of UDCA and CUDCA A-D were built by using molecular computer graphic techniques. It was shown that the four diastereoisomers greatly differ in hydrophilicity, in critical micellar concentration (CMC) in water, and exhibit a different interaction with intestinal bacterial enzymes. It was also shown that CUDCA A-C are not conjugated with glycine or taurine in the liver, while CUDCA D is secreted into bile predominantly as taurine and glycine conjugate. PMID- 3351849 TI - The importance of residues 2 (arginine) and 6 (histidine) in high-affinity angiotensin II antagonists. AB - The structure-antagonist activity relationship is described for analogues of [Sar1,Ile8]angiotensin II substituted in position 2 (arginine) and position 6 (histidine). An extreme sensitivity of potency to alterations in these positions was observed, suggesting that both residues are important for binding. Evidence is presented suggesting that the position 6 histidine side chain in angiotensin II (AII) is not involved in receptor stimulation. The structure-activity relationship is also explored for both [des-Asp1] AII (AIII) and [des Asp1,Ile8]AII analogues substituted in position 2 (arginine). The substitution of D-N-methylalanine, D-(NMe)Ala, into position 2 of both [des-Asp1]AII and [des Asp1,Ile8]AII gives analogues 39 and 40 that appear to be more potent than the native [Arg2]peptides and that are the most potent AIII agonists and antagonists described to date. PMID- 3351851 TI - Photoaffinity labeling adenosine A1 receptors with an antagonist 125I-labeled aryl azide derivative of 8-phenylxanthine. AB - We have derivatized a series of 125I-labeled 8-phenylxanthines with photoactive aryl azide groups on the 1- or 3-position of the xanthine ring. A 3 azidophenethyl derivative was found to be optimal for use as an antagonist photoaffinity label for adenosine A1 receptors. Following photoactivation, radioactivity was covalently and specifically incorporated into a 34,000-dalton and, to a lesser extent, into a 24,000-dalton polypeptide of rat brain membranes. Photoincorporation into both polypeptides was competitively inhibited by adenosine analogues with a potency order typical of adenosine A1 receptors, but the 24,000-dalton polypeptide bound both agonists and antagonists with lower affinity than the 34,000-dalton polypeptide. Specific photolabeling of receptors in brain membranes of rat, guinea pig, dog, and cow did not show any variation in the 34,000-dalton adenosine receptor binding subunit. The adenosine agonist photoaffinity label [125I]N6-(4-azido-3-iodobenzyl)adenosine also specifically photolabeled the 34,000-dalton polypeptide, but photoincorporation of the agonist was less efficient than the antagonist and, unlike the antagonist, was greatly reduced by guanosine 5'-(beta,gamma-imidotriphosphate). The results indicate that the antagonist photoaffinity label may be more useful than agonists particularly for labeling uncoupled receptors. PMID- 3351850 TI - 125I-labeled 8-phenylxanthine derivatives: antagonist radioligands for adenosine A1 receptors. AB - A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 adenosine receptors of bovine and rat brain and A2 receptors of human platelets was examined. The addition of arylamine or photosensitive aryl azide groups to the 3-position of xanthine had little effect on A1 binding affinity with or without iodination, whereas substitutions at the 1-position caused greatly reduced A1 binding affinity. The addition of an aminobenzyl group to the 3-position of the xanthine had little effect on A2 binding affinity, but 3 aminophenethyl substitution decreased A2 binding affinity. Two acidic 3 (arylamino)-8-phenylxanthine derivatives were labeled with 125I and evaluated as A1 receptor radioligands. The new radioligands bound to A1 receptors with KD values of 1-1.25 nM. Specific binding represented over 80% of total binding. High concentrations of NaCl or other salts increased the binding affinity of acidic but not neutral antagonists, suggesting that interactions between ionized xanthines and receptors may be affected significantly by changes in ionic strength. On the basis of binding studies with these antagonists and isotope dilution with the agonist [125I]N6-(4-amino-3-iodobenzyl)adenosine, multiple agonist affinity states of A1 receptors have been identified. PMID- 3351852 TI - Sulfur derivatives of 2-oxopropanal oxime as reactivators of organophosphate inhibited acetylcholinesterase in vitro: synthesis and structure-reactivity relationships. AB - We have prepared four new oximes, 1b-e, which conform to the general structure RCH2COCH = NOH where R = CH3S, CH3SO, CH3SO2, and (CH3)2S+, respectively, and have the same E configuration as the parent 2-oxopropanal oxime 1a (R = H, MINA). The pKa values range from 6.54 (1e) to 8.16 (1b), as compared with 8.30 for 1a. Rates of reaction (kappa 1) with 4-nitrophenyl acetate indicate that the oximate anions have a much higher nucleophilicity than common oxyanions of similar basicities: the alpha effects measured for 1a-e are of the order of 200-250. The abilities of 1b-e to reactivate acetylcholinesterase (AChE) inhibited by organophosphates have been evaluated. In vitro experiments reveal a significant reactivation potency of 1b-e against VX-, sarin-, and paraoxon-inhibited immobilized eel AChE. The highly lipophilic methylthio oxime 1b (log P greater than 1) is intrinsically (kappa 2) 3 times more reactive than the more basic MINA (log P less than 1). The sulfonium oxime 1e is a potent reactivator against paraoxon. Interestingly, both 1b and 1e have a low toxicity and they exhibit a significant antidotal effect at a relative low dose against paraoxon in rats. PMID- 3351853 TI - Methotrexate analogues. 31. Meta and ortho isomers of aminopterin, compounds with a double bond in the side chain, and a novel analogue modified at the alpha carbon: chemical and in vitro biological studies. AB - Five heretofore undescribed analogues of methotrexate (MTX) and aminopterin (AMT) were synthesized and tested as dihydrofolate reductase (DHFR) inhibitors and tumor cell growth inhibitors. The meta isomer of AMT was obtained from 2,4 diamino-6-(bromomethyl)pteridine and m-(aminobenzoyl)-L-glutamic acid, while the ortho isomer was obtained via the same route by using alpha-methyl gamma-tert butyl o-(aminobenzoyl)-L-glutamate instead of the free acid. Analogues of MTX and AMT containing a double bond in the side chain were prepared from dimethyl D,L-2 amino-4-hexenedioate and 4-amino-4-deoxy-N10-methylpteroic acid and 4-amino-4 deoxy-N10-formylpteroic acid, respectively. Finally, a positional isomer of MTX with the CH2CH2COOH moiety moved from the alpha-carbon to the adjacent carboxamide nitrogen was synthesized from 3-[N-(carboxymethyl)amino]propanoic acid diethyl ester and 4-amino-4-deoxy-N10-methylpteroic acid. The positional isomers of AMT were weak DHFR inhibitors and showed very little growth-inhibitory activity against L1210 murine leukemia cells or the MTX-resistant L1210/R81 mutant line in culture. The MTX and AMT analogues with the CH2CH2COOH moiety replaced by a CH2CH = CHCOOH side chain showed anti-DHFR activity similar to that of the previously described saturated compound N-(4-amino-4-deoxy-N10 methylpteroyl)-L-2-aminoadipic acid, but were less potent than the parent drugs. The MTX analogue with the CH2CH2COOH side chain displaced from C to N was weakly bound to DHFR, confirming the importance of an intact CONH moiety, and showed greatly diminished cell growth inhibitory potency relative to MTX. None of the compounds was a substrate for folylpolyglutamate synthetase (FPGS) from mouse liver. Furthermore, inhibition of folic acid polyglutamylation in vitro at equimolar 500 microM concentrations of drug and substrate was negligible. The structural changes embodied in these five novel compounds are therefore too great for binding to the FPGS active site. PMID- 3351854 TI - New actinomycin D analogues as superior chemotherapeutic agents against primary and advanced colon tumors and colon xenografts in nude mice. AB - "Reverse" analogues (RAD's) of actinomycin D (AMD) and their antitumor activity against mouse and human colon tumor cells are reported. RAD's are tetracyclic, and they have an oxazole ring fused on the tricyclic phenoxazine chromophore of AMD. The oxazole ring in RAD is substituted at the C-2 carbon with either a CH3 (in RAD I), a C6H5 (in RAD II), or a CH2CONH(CH2)4NH2 (in RAD III) group. In tumor cells and rat hepatic microsomes, RAD's are metabolized to a tricyclic "symmetrical" analogue of AMD (SAD) with the loss of the oxazole ring and its substituents. RAD and SAD are very active in priming superoxides in the presence of microsomal enzymes as well as in inhibiting the synthesis of DNA and the growth of human colon tumor HT-29 cells in vitro. RAD III and SAD efficiently cleave closed circular plasmid pBR322 DNA like the antitumor agent bleomycin. In addition to their strong inhibitory activity against P388 and B16 tumors in vitro and in vivo, RAD III and SAD demonstrate high levels of activity against primary C26 and advanced C38 colon tumors in mice and against a xenograft of human colon adenocarcinoma CX-1 in athymic mice. In all these biological activities, the analogues demonstrate superiority to AMD in several experimental tumors. Also, the analogues, in contrast to AMD, show reduced toxicity in tumor-free mice, which is possibly due to the metabolic deactivation of SAD in host organs. PMID- 3351855 TI - Potential antitumor agents. 55. 6-Phenylphenanthridine-4-carboxamides: a new class of DNA-intercalating antitumor agents. AB - Derivatives of the DNA-intercalating agent N-[2 (dimethylamino)ethyl]phenanthridine-4-carboxamide have been prepared and shown to have moderate in vivo antitumor activity against both the P388 leukemia and Lewis lung carcinoma. This demonstrates that the effective pharmacophore in the broad class of tricyclic carboxamides is not limited to linear tricyclic chromophores. Both 7 and the 6-phenyl derivative 10 have identical DNA binding properties, suggesting that the phenyl ring of 10 is not involved in the DNA intercalation site. A series of phenyl-substituted derivatives of 10 was evaluated. Aza substituents led to compounds with the highest in vivo cytotoxicity and in vivo P388 activity, but the in vivo solid tumor activity of the substituted 6 phenylphenanthridine-4-carboxamides was in general low. PMID- 3351856 TI - Synthesis and antiulcer activity of 5,11-dihydro[1]benzoxepino[3,4-b]pyridines. AB - A series of substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines was synthesized and evaluated for antiulcer activity in water immersion/restrained stress ulcer assay in rats. Structure-activity relationships are described. Most of the tested compounds exhibited low affinity to the muscarinic acetylcholine receptor. The molecular features for the best activities are the 2 (diethylamino)ethylenediamine group at the 5-position of the oxepin ring and an oxepin skeleton rather than a thiepin or a pyran skeleton. Methyl and chlorine substitution on the benzene ring reduced the activity. Compound 11, 5-[[2 (diethylamino)ethyl]amino]-5,11-dihydro[1]benzoxepino [3,4-b]pyridine trihydrochloride was selected for further evaluation. Synthesis and antiulcer activity of optically active 11 is described. There were no statistically significant differences between (+)-, (-)-, and (+/-)-11. Compound 11 showed weak antisecretory activity in pylorus-ligated rats. It is now under clinical evaluation as KW 5805. PMID- 3351857 TI - Synthesis, intramolecular hydrogen bonding, and biochemical studies of clitocine, a naturally occurring exocyclic amino nucleoside. AB - The total synthesis of clitocine [6-amino-5-nitro-4-(beta-D ribofuranosylamino)pyrimidine] (1), a nucleoside recently isolated from the mushroom Clitocybe inversa, has been accomplished. Glycosylation of 4,6-diamino-5 nitropyrimidine (4) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose afforded the protected nucleoside 6-amino-5-nitro-4-[(2,3,5-tri-O-benzoyl-beta-D ribofuranosyl) amino]pyrimidine (5) in good yield exclusively as the beta-anomer. Deprotection of 5 with NaOMe/MeOH gave 1 as an 11.5:1 mixture of the beta- and alpha-anomers, respectively. Recrystallization from MeOH, followed by chromatography, afforded 1 containing less than 1% of its alpha-anomer. X-ray crystal data revealed a planar aglycon moiety in clitocine with each oxygen atom of the nitro group intramolecularly hydrogen bonded to the hydrogen atoms of the two adjacent amino functions. Clitocine inhibited L1210 cells in vitro with an ID50 of 3 X 10(-8) M. Clitocine was also found to be a substrate and inhibitor of adenosine kinase with a Ki value of 3 X 10(-6) M. PMID- 3351858 TI - Studies on scavengers of active oxygen species. 1. Synthesis and biological activity of 2-O-alkylascorbic acids. AB - A novel series of 2-O-alkylascorbic acids (5a-u) was synthesized, and their scavenging activities against active oxygen species as well as their suppressive effects on the arrhythmias in rat heart ischemia-reperfusion models were evaluated. Some 2-O-alkylascorbic acids (5e-1) exhibited potent inhibiting activities against lipid peroxidation in rat brain homogenates and in alleviating effects in the ischemia-reperfusion models. Studies on the structure-activity relationship demonstrated that a free 3-enolic hydroxyl group and the longer alkyl chains substituted on the 2-hydroxyl group of ascorbic acid were beneficial for the biological and pharmacological activities. 2-O-Octadecylascorbic acid (5k, CV-3611), one of the most potent and promising compounds, markedly inhibited lipid peroxidation (IC50 = 4.3 X 10(-6) M) and alleviated myocardial lesions induced by ischemia-reperfusion at an oral dose of 1 mg/kg in rats. PMID- 3351859 TI - Flavins as potential antimalarials. 1. 10-(Halophenyl)-3-methylflavins. PMID- 3351860 TI - Approaches to protection against nerve agent poisoning. (Naphthylvinyl)pyridine derivatives as potential antidotes. AB - Analogues of the potent inhibitor of choline acetyltransferase (CAT) (E)-4-(1 naphthylvinyl)pyridine methiodide were synthesized and evaluated for their ability to inhibit CAT and protect against nerve agent intoxication. Several compounds, notably (E)-1-(2-hydroxyethyl)-(1-naphthylvinyl)pyridinium bromide (3), (E)-1-methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine hydrochloride (22), and (E)-1-methyl-4-(1-naphthylvinyl)piperidine hydrochloride (23), were found to afford significant protection against sarin in the mouse and against soman in the guinea pig. However, protection was apparently not related to CAT inhibition. Compound 23, our most effective compound in protecting against nerve agent, was without CAT inhibitory activity. Compound 22, which proved to be a potent CAT inhibitor, most likely owed this activity to being dehydrogenated back to the pyridinium quaternary salt by oxidative enzymes. Several of the (naphthylvinyl)pyridine quaternary salts, but not their tertiary amine analogues, were found to be effective in slowing the rate of aging of soman-inhibited acetylcholinesterase. Ability to slow the rate of aging was enhanced by introduction of methoxy substituents on the aryl moiety whereas the aging rate was actually accelerated by chloro substituents. To date, our most effective compound in slowing the rate of aging, (E)-4-[(4-methoxy-1 naphthyl)vinyl]pyridine methochloride (6), did not provide significant protection against soman in the mouse. PMID- 3351861 TI - Synthesis and evaluation of 3-substituted analogues of 1,2,3,4 tetrahydroisoquinoline as inhibitors of phenylethanolamine N-methyltransferase. AB - 1,2,3,4-Tetrahydroisoquinoline (THIQ) and aryl-substituted derivatives of THIQ are potent inhibitors of the enzyme that catalyzes the formation of epinephrine- phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28). In previous studies, we found that substitution of the 3-position of THIQ with a methyl group resulted in enhanced activity as an inhibitor for 3-methyl-THIQ with respect to THIQ itself. To more fully delineate this region of the PNMT active site, we have synthesized and evaluated other 3-substituted THIQ analogues that vary in both steric and electronic character. Extension of the methyl side chain in 8 by a single methylene unit results in diminished potency for 3-ethyl-THIQ, suggesting that this zone of the active site is spatially compact; furthermore, the region of steric intolerance may be located principally on only "one side" of the 3 position of bound THIQs, since the carbonyl containing (bent) analogues 3 (methoxycarbonyl)-THIQ and 3-(aminocarbonyl)-THIQ are much less capable of forming a strong enzyme-inhibitor dissociable complex compared to straight-chain derivatives possessing a similar steric component. The good activity of 3 (hydroxymethyl)-THIQ as a PNMT inhibitor cannot be explained solely by steric tolerance for this side chain. We believe that an active-site amino acid residue capable of specific (i.e., hydrogen bond) interactions is located in close proximity to the 3-position of bound THIQs and that association of the OH functionality with this active-site residue results in the enhanced in vitro potency of this analogue (Ki = 2.4 microM) compared to that of THIQ (Ki = 10.3 microM). Incorporation of a hydroxymethyl substituent onto the 3-position of the potent PNMT inhibitor 7,8-dichloro-THIQ (SKF 64139, Ki = 0.24 microM) did not result in the same enhancement in inhibitor potency for 17 (Ki = 0.38 microM). This result suggests that simultaneous binding in an optimal orientation of the aromatic halogens, secondary amine, and side-chain hydroxyl functionalities to the PNMT active site is not allowed in this analogue. PMID- 3351862 TI - 3-Phenoxypyridine 1-oxides as anticonvulsant agents. AB - The anticonvulsant activity of a series of 3-phenoxypyridine 1-oxides is described. An investigation carried out to optimize the activity/side effect ratio provided 4-methyl-3-phenoxypyridine 1-oxide, 3, as the derivative of choice. Overall, 3 has a pharmacological profile that is very similar to phenytoin. It exhibited significant anticonvulsant activity at doses that did not produce ataxia or sedation but caused increased spontaneous behavioral activity not seen with most anticonvulsants. The short duration of pharmacological effect of 3 was attributed to metabolic hydroxylation at the C-4 pyridine methyl group; however, structural modifications designed to inhibit this metabolic pathway were unsuccessful. PMID- 3351863 TI - Synthesis, molecular modeling, DNA binding, and antitumor properties of some substituted amidoanthraquinones. AB - A series of 1- and 1,4-substituted amidoanthraquinones have been prepared, with side chains possessing basic nitrogen atoms. Computer modeling and energy calculations have shown that all eight compounds can bind intercalatively to DNA and that there are significant differences in the additional nonbonded and electrostatic interactions possible at the DNA binding site. Solution DNA binding and closed-circular DNA unwinding studies confirmed intercalative interactions, and the predicted differences in strength of interactions between mono- and disubstituted compounds were found. All compounds were modestly cytotoxic to L1210 cells in culture. In vivo activity against L1210 and S180 tumors was not found for the monosubstituted compounds, whereas the four disubstituted ones had varying levels of measurable, though low, activity. PMID- 3351864 TI - Synthesis, resolution, and absolute configuration of the isomers of the neuronal excitant 1-amino-1,3-cyclopentanedicarboxylic acid. AB - The endogenous amino acids glutamate and aspartate depolarize mammalian neurons to produce excitation, and the rigid glutamate analogue 1-amino-1,3 cyclopentanedicarboxylic acid also has this effect. This compound exists as two pairs of geometric isomers, and in the present study the absolute configuration of the four isomers is assigned. The known (+)-S and (-)-R isomers of 3 oxocyclopentanecarboxylic acid were used as the basis for the synthesis. The cis and trans amino acids were obtained by fractional crystallization. Spectral data, including optical rotation, circular dichroism, and 13C nuclear magnetic resonance, are presented. The compounds were evaluated as excitants by microiontophoretic ejection into the dendritic region of impaled CA1 pyramidal neurons of rat hippocampal slices. One isomer, cis-1R,3R, mimicked completely the actions elicited by N-methyl-D-aspartic acid; the other three isomers were alpha kainic acid like. PMID- 3351865 TI - Resolution of the nonsteroidal antiandrogen 4'-cyano-3-[(4-fluorophenyl)sulfonyl] 2-hydroxy-2-methyl-3'- (trifluoromethyl)-propionanilide and the determination of the absolute configuration of the active enantiomer. AB - The nonsteroidal antiandrogen 4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2- hydroxy-2 methyl-3'-(trifluoromethyl)-propionanilide (1) (ICI 176334) has been resolved by chromatographic separation of the diastereomeric (R)-camphanyl esters of the precursor thioether 2 followed by hydrolysis and oxidation of the isolated enantiomers. In addition, an asymmetric synthesis of (S)-3-bromo-2-hydroxy-2 methylpropanoic acid (11) and subsequent conversion into the (S)-sulfone 6a has established that the more potent enantiomer of 1 has the R absolute configuration. PMID- 3351866 TI - Seasonal variation in body size and the relationships among body size, parity, and fecundity of host-seeking Tabanus quinquevittatus females (Diptera: Tabanidae). PMID- 3351867 TI - Hosts and population dynamics of Amblyomma variegatum (Acari: Ixodidae) on Guadeloupe, French West Indies. PMID- 3351869 TI - Caloric determinations of phlebotomine sand flies (Diptera: Psychodidae). PMID- 3351870 TI - The pattern of Dermatobia (Diptera: Cuterebridae) myiasis in cattle in tropical Mexico. PMID- 3351868 TI - Parity and voltinism of several Culicoides spp. (Diptera: Ceratopogonidae) in Israel, as determined by two trapping methods. PMID- 3351871 TI - Abnormal development of Amblyomma variegatum (Acarina: Ixodidae). PMID- 3351873 TI - A new ligation technique for soft ticks (Acari: Argasidae). PMID- 3351872 TI - Lack of behavioral responses of the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae), to a broad spectrum of ultrasound. PMID- 3351874 TI - Hosts of Anopheles earlei Vargas (Diptera: Culicidae) in southwestern Manitoba. PMID- 3351875 TI - Chromosomes, reproductive biology, and developmental stages of Aponomma varanensis (Acari: Ixodidae). PMID- 3351876 TI - Lone star tick (Acari: Ixodidae) management by host manipulation through habitat modification. PMID- 3351877 TI - Sex ratios of Boophilus ticks (Acari: Ixodidae) reaching adulthood on cattle. PMID- 3351878 TI - Metabolism of coumaphos in susceptible and resistant strains of Boophilus microplus (Acari: Ixodidae). PMID- 3351880 TI - Pregnancy, obstetrics and the moral status of the fetus. PMID- 3351879 TI - Technical expertise as an ethical form: towards an ethics of distance. AB - The present article proceeds from the observation that the therapeutic relationship is basically unequal. This inequality essentially concerns the respective situation of the patient and his or her doctor vis-a-vis medical knowledge. A strict professionalism guarantees that this inequality remains factual and without essential value. Yet, if both partners unreflectively allow affectivity excessively to intrude into their relationship, their behaviour may then be inspired by subconscious, rather than rational, motives. In that case, the unverifiable allegations of philanthropy or paternalism may be used to rationalise a kind of 'medical sadism' which attempts to justify the will to humiliate the patient by means of the constraints inherent in medical care. The concept of ethical form is introduced as a non-verbal criterion of ethical reliability. It is mainly a way of training the will through the application of rationally justified rules of behaviour. In this context, it is suggested that an effort to remain constantly within the limits of professionalism represents a method of training for the achievement of some degree of ethical credibility in the therapeutic relationship. In the long term, such abstinence could constitute a sort of catharsis, and thereby help to reveal the non-rational motives in medical behaviour. Contrary to the belief prevailing in modern society, the established limits of medical knowledge are not so broad. The application of these limits would probably be the best method of preventing emotions from interfering undesirably in the therapeutic relationship. PMID- 3351881 TI - Ethical dilemmas in pharmacy. AB - Results of surveys in which pharmacy students and pharmacists responded to ethical dilemmas are discussed. Respondents indicated a high level of concern about patient welfare and patient rights in dilemmas involving conflicts with socio-economic issues, and with peers and physicians. Conflicts that might arise as the roles of pharmacists change and the health-care systems evolve are also discussed. PMID- 3351882 TI - Attempting to demystify law reports for the non-lawyer. AB - To a non-lawyer, references to law reports can appear confusing and complicated. This brief article attempts to explain how to decode such references and thus get to the reports. Those wishing to pursue the matter further are referred to more detailed explanations. This article deals primarily with English case law and is up to date as of December 1987. PMID- 3351884 TI - Competition in medical ethics. Persons and values. PMID- 3351883 TI - Competition in medical ethics. PMID- 3351885 TI - Competition in medical ethics. Would it have been better had he died? A case conference. PMID- 3351886 TI - Ian Ramsey and the practice of medicine. PMID- 3351887 TI - The patient advocate as adversary. PMID- 3351888 TI - Polymorphic acetylation of sulphamethazine in a Zimbabwe population. AB - Sulphamethazine, 8 mg/kg body weight, was administered orally in tablet form to 100 healthy volunteers and total and free sulphamethazine were determined in the six hour urine sample. The bimodal population frequency distribution for percentage acetylated sulphamethazine showed 42 of the tested population to be fast and 58 to be slow acetylators, that is, an estimation of q = 0.72 +/- 0.3 as the frequency of the allele controlling slow acetylation. The study also revealed ample evidence that the assay of the drug in urine can be done in a significantly shorter time. PMID- 3351889 TI - Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association. AB - We report a sibship of two brothers and one sister with the osteoporosis pseudoglioma syndrome and congenital heart disease. They presented in infancy with visual impairment and psychomotor retardation. Major features included bilateral cataracts, generalised osteopenia, severe platyspondyly, borderline mental retardation, muscular hypotonia, joint laxity, and ventricular septal defect. Parental consanguinity and affected sibs of both sexes strongly suggested autosomal recessive inheritance. Analysis of the present and previously reported cases showed a wide range of interfamilial variability which may point to the existence of multiple allelism or genetic heterogeneity in this syndrome. PMID- 3351890 TI - Iris coloboma, ptosis, hypertelorism, and mental retardation: a new syndrome. AB - To sibs and an unrelated single patient have a combination of iris coloboma, ptosis, hypertelorism, broad nasal bridge, short stature, and mental retardation. The London Dysmorphology Database was used to determine whether this is a new syndrome. PMID- 3351891 TI - Association of an ataxia indistinguishable from Friedreich's ataxia and congenital glaucoma in a family: a new syndrome. AB - An inbred family is described in which three sibs have congenital glaucoma and two of them also have an ataxia indistinguishable from Friedreich's ataxia. The association between these two disorders has not previously been reported. The genetic mechanisms of this association are discussed. PMID- 3351892 TI - Prenatal diagnosis of inv(X)(q12q28) in a male fetus. AB - Amniocentesis and prenatal chromosome analysis were performed for advanced maternal age. The fetus was male with a paracentric inversion in the long arm of the X chromosome. The mother and a brother also carried the inversion. The pregnancy continued to term and the infant is developing normally at one year of age. PMID- 3351893 TI - A recognisable short stature syndrome with premature aging and pigmented naevi. AB - We report the progress up to the age of seven years of a small for dates baby whose face and neck are strikingly devoid of subcutaneous tissue and who has, in addition, multiple pigmented naevi. PMID- 3351894 TI - VATER association: report of a case with three unreported malformations. AB - The VATER association is the sporadic non-random association of Vertebral anomalies, Anal atresia, Tracheo-oesophageal fistula with Esophageal atresia, Renal defects, and Radial limb dysplasia. Cardiac defects are common, as are other limb malformations. The present report describes a premature infant with most of the known major and minor defects of the association as well as agenesis of the bladder and penis and an askeletal rudimentary tail. The latter have not previously been described. PMID- 3351895 TI - Two whole arm reciprocal translocations. PMID- 3351896 TI - Royal Society discussion meeting: Prevention and Avoidance of Genetic Disease, held on 29 to 30 April 1987 at the Royal Society. PMID- 3351897 TI - Expression of fragile X chromosome and possible deletion in successive cell divisions. PMID- 3351898 TI - Noonan syndrome. PMID- 3351899 TI - The population genetics of Duchenne muscular dystrophy. PMID- 3351900 TI - A reappraisal of the CHARGE association. AB - We describe 14 boys and six girls, including monozygotic twins, with the CHARGE association. All of the children had at least four of the seven major features included in the mnemonic CHARGE and all had ear anomalies or deafness or both and either coloboma or choanal atresia or both. All the boys had evidence of hypogonadism. A characteristic facial appearance (unusually shaped ears, unilateral facial palsy, square face, malar flattening, pinched nostrils) was observed in many of our cases. The aetiology remains unknown. All our cases are sporadic. PMID- 3351901 TI - Further delineation of the G syndrome: a manageable genetic cause of infantile dysphagia. AB - Three families including five subjects with the G or Opitz-Frias syndrome are added to 23 published cases who had dysphagia; characteristics of the two affected relatives were added to 19 well documented published reports. The data from index cases support the concept of the G syndrome as a constellation of midline defects, which include hypertelorism or telecanthus (89%), oesophageal dysmotility (69%), laryngotracheal clefts (44%), cleft palate or bifid uvula (34%), heart defects (29%), hypospadias (100% of males), renal or ureteral anomalies (42%), and mental retardation (38%). Affected relatives, often identified by hypertelorism, dysphagia, or hypospadias, had a much lower incidence of associated defects and mental retardation. They provide a more rounded but still biased view of a syndrome compatible with normal intelligence and life span. The data do not support a highly characteristic face in the G syndrome, which discriminates it from the phenotypically similar BBB syndrome. The variable expressivity and five cases of male to male transmission observed in 18 families are consistent with autosomal dominant inheritance. Vigilance for the morphological characteristics of G syndrome in patients with dysphagia is underscored by the potential for normal development with appropriate intervention. PMID- 3351902 TI - Intellectual development in Apert's syndrome: a long term follow up of 29 patients. AB - Twenty-nine patients with Apert's syndrome were ascertained through hospital records. The mean age was 19.3 years (range eight to 35 years). Further information was obtained on their intelligence, education, and employment records. Fourteen patients (48%) had a normal or borderline IQ (greater than 70), nine patients (31%) were mildly mentally retarded (IQ 50 to 70), four patients (14%) were moderately retarded (IQ 35 to 49), and two patients (7%) were severely retarded (IQ less than 35). Early craniectomy did not appear to improve intellectual outcome. Six of the seven school leavers with normal or borderline intelligence were in full time employment or vocational training. PMID- 3351903 TI - Familial spastic paraplegia, bilateral sensorineural deafness, and intellectual retardation associated with a progressive nephropathy. AB - We present a family in which at least four persons have evidence of an inherited disorder comprising a variable spastic paraplegia, bilateral sensorineural deafness, intellectual retardation, and a progressive nephropathy. Focal segmental proliferative lesions with sclerosis suggestive of mesangial IgA nephropathy (Berger's disease) were found on renal renal biopsy in two affected persons. The glomerular basement membrane showed none of the changes characteristic of Alport's syndrome. Males and females are affected and the segregation of the disease is consistent with dominant transmission. PMID- 3351905 TI - Family size limitation: a method for demonstrating recessive inheritance. AB - Limitation of family size after the birth of a child with a serious disorder poses a problem in demonstrating autosomal recessive inheritance. In this paper methods are presented for distinguishing autosomal recessive inheritance given a 100% deterrent effect, and revealing a partial deterrent effect by analysis of sibship size and comparison with general population data. These methods are illustrated using information from phenylketonuria families. PMID- 3351906 TI - The frequency of consanguineous marriage among British Pakistanis. AB - An enquiry answered by 100 randomly selected British Pakistani mothers in the postnatal wards of two hospitals in West Yorkshire showed that 55 were married to their first cousins, while in only 33 cases had their mother been married to her first cousin. This suggests an increasing rate of consanguineous marriage in this relatively small group, by contrast with the decreasing rate observed in some other countries. The genetic implications merit further study. PMID- 3351904 TI - Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome. AB - Instability of the heterochromatic centromeric regions of chromosomes 1, 9, and 16 associated with immunodeficiency was found in a four year old girl. Similar phenotypic and chromosomal abnormalities were described in a previous patient studied by us and in four other published cases. All these patients have facial anomalies in addition to combined immunodeficiency and chromosomal instability. Stretching of the heterochromatic centromeric regions of chromosomes 1, 16, and to a lesser extent, 9 and homologous and non-homologous associations of these regions were the most common cytogenetic findings in all the patients. Multi branched configurations and whole arm deletions of chromosomes 1 or 16 or both were also found. Comparing clinical and chromosomal data we conclude that immunodeficiency, centromeric heterochromatin instability, and facial anomalies form a new syndrome, for which we propose the acronym ICF. A mutation interfering with the normal process of condensation of part of the centromeric heterochromatin is postulated as the basic chromosome defect in this syndrome. PMID- 3351908 TI - Sclerosteosis. PMID- 3351907 TI - Clinical, haematological, and genetic studies of type 2 normal Hb A2 beta thalassaemia. AB - The clinical and haematological phenotype as well as chain synthesis data were studied in 35 doubly heterozygous patients with either normal Hb A2 and Hb F, type 2 beta thalassaemia and beta (high A2) thalassaemia (26 patients), or type 2 and other rare beta or delta beta variants (nine patients). Patients doubly heterozygous for type 2 and beta zero or delta beta zero thalassaemia variants had no detectable Hb A, indicating that the type 2 normal A2 beta thalassaemia is primarily the result of a beta zero gene. The clinical phenotype varied from severe thalassaemia major to mild thalassaemia intermedia, and was mainly related to the thalassaemia variant with which the type 2 normal A2 beta thalassaemia was combined, and the proportion of Hb A produced in beta + thalassaemia patients. Haematological and chain synthesis data were similar in heterozygotes with type 2 and beta zero or beta + (high A2) thalassaemia. Hb A2 levels were within the normal range (2.3 to 3.6%) though absolute values (Hb A2 per RBC) ranged from low normal (0.5 pg/RBC) to increased levels (1.0 pg/RBC.) The variation of Hb A2, as well as the presence of Hb A2 in a type 2/delta beta high F patient and the complete absence of HbA2 in a homozygous type 2 patient, indicate that there are at least two genotypes of type 2, one beta zero and the other delta beta zero. This has been recently proven by gene mapping studies. For clinicians, routine haematological and family studies are sufficient for the proper treatment and prevention of doubly heterozygous type 2 patients. PMID- 3351909 TI - Hirschsprung disease associated with polydactyly, unilateral renal agenesis, hypertelorism, and congenital deafness: a new autosomal recessive syndrome. AB - An association of Hirschsprung disease with polydactyly, unilateral renal agenesis, hypertelorism, and congenital deafness is described in sibs (brother and sister) of consanguineous parents. It is suggested that this might represent a new autosomal recessive syndrome. PMID- 3351910 TI - Unusual dual genital duct remnants in true hermaphroditism. AB - A case of true hermaphroditism is reported in which a 46,XY karyotype was associated with a testis and an ovotestis. The dual presence of a Fallopian tube and a vas deferens on the side of the ovotestis is documented as a previously unreported finding. PMID- 3351911 TI - De novo 10q23 interstitial deletion. PMID- 3351912 TI - Interstitial deletion (6) (q11----q15) in an infant with congenital abnormalities. PMID- 3351913 TI - Terminal deletion of chromosome 1(q43) in a female infant. PMID- 3351914 TI - Anomalous X chromosome inactivation: the link between female zygotes, monozygotic twinning, and neural tube defects? PMID- 3351916 TI - Pressure-induced dissociation of brome mosaic virus. AB - Brome mosaic virus reversibly dissociates into subunits in the pressure range of 600 x 10(5) to 1600 x 10(5) Pa, as demonstrated by studies of the spectral shift of intrinsic fluorescence, of filtration chromatography and of electron microscopy of samples fixed under pressure. Smaller shell particles (T = 1) were detected as intermediates in the dissociation pathway. Dissociation was facilitated by decreasing the concentration, as expected for a multimolecular reaction. The estimated change in volume upon dissociation into 90 dimer particles was -2960 ml/mol. Large increases in the intrinsic fluorescence intensity and in the binding of bis(8-anilinonaphthalene-1-sulfonate) occurred at pressures higher than 1400 x 10(5) Pa. The pressure-dependence profile of the different spectral properties shifted to lower pressures when 5 mM-MgCl2 was included in the buffer or when the pH was raised from 5.5 to 5.9. When the pressure was progressively increased above 1400 x 10(5) Pa, a value that led to 75% dissociation, the capsid subunits lost the ability to reassociate into regular shells and only amorphous aggregates were formed after decompression, as evidenced by both electron microscopy and gel filtration chromatography. The formation of these random aggregates of brome mosaic virus can be explained by a conformational drift of the separated subunits, similar in nature to that found in simpler oligomeric proteins. PMID- 3351915 TI - Genomic organization of major sperm protein genes and pseudogenes in the nematode Caenorhabditis elegans. AB - The major sperm proteins (MSPs) are a family of closely related, small, basic proteins comprising 15% of the protein in Caenorhabditis elegans sperm. They are encoded by a multigene family of more than 50 genes, including many pseudogenes. MSP gene transcription occurs only in late primary spermatocytes. In order to study the genomic organization of transcribed MSP genes, probes specific for the 3' untranslated regions of sequenced cDNA clones were used to isolate transcribed genes from genomic libraries. These and other clones of MSP genes were located in overlapping cosmid clones by DNA fingerprinting. These cosmids were aligned with the genetic map by overlap with known genes or in-situ hybridization to chromosomes. Of 40 MSP genes identified, 37, including all those known to be transcribed, are organized into six clusters composed of 3 to 13 genes each. Within each cluster, MSP genes are not in tandem but are separated by at least several thousand bases of DNA. Pseudogenes are interspersed among functional genes. Genes with similar 3' untranslated sequences are in the same cluster. The six MSP clusters are confined to only three chromosomal loci; one on the left arm of chromosome II and two near the middle of chromosome IV. Additional sperm specific genes are located in one cluster of MSP genes on chromosome IV. The multiplicity of MSP genes appears to be a mechanism for enhancing MSP synthesis in spermatocytes, and the loose clustering of genes could be a result of the mechanism of gene duplication or could play a role in regulation. PMID- 3351917 TI - Crystals of a nucleosome core particle containing defined sequence DNA. AB - Nucleosome core particles were reconstituted from a DNA restriction fragment and histone octamers, crystallized, and the crystals examined by X-ray diffraction. A DNA fragment was engineered by site-directed mutagenesis to obtain a 146 base pair sequence that takes up a symmetrical arrangement in the core particle. The resulting DNA sequence was cloned in multiple copies into pUC9 and excised as monomer via EcoRV to produce it in milligram quantities. Nucleosome core particles incorporating the DNA were reconstituted by salt gradient dialysis and purified by anion-exchange high-pressure liquid chromatography. DNase I digestion was used to demonstrate that the termini of the restriction fragment are located 73 base-pairs from the molecular dyad axis of the particle. The diffraction limits of crystals of defined sequence core particles extend along the principal direction to a approximately equal to 4 A, b approximately equal to 5 A and c approximately equal to 3 A, giving about a twofold increase in the number of measurable X-ray reflections over previous crystals containing mixed sequence DNA. The methods developed here should be useful in the study of other large protein-DNA complexes. PMID- 3351918 TI - Tertiary structure of Bacillus thermoproteolyticus [4Fe-4S] ferredoxin. Evolutionary implications for bacterial ferredoxins. AB - The structure of a low-potential [4Fe-4S] ferredoxin from Bacillus thermoproteolyticus has been solved using anomalous scattering data from iron atoms in the diffraction data of native crystals and refined partially to a crystallographic R-factor of 0.33, with 2.3 A (1 A = 0.1 nm) resolution data. The least-squares refinement based on the Bijvoet differences has determined that the four iron atoms in the cluster are an equal distance, approximately 2.8 A, apart. The NH ... S hydrogen bonds between polypeptide nitrogen atoms, and both cysteine and inorganic sulfur atoms, are present, as in ferrodoxin from Peptococcus aerogenes. The polypeptide chain of the B. thermoproteolyticus ferredoxin has a fold closely similar to that of 2[4Fe-4S] ferredoxin from P. aerogenes. The structural correspondence indicates strongly that both types of ferredoxin evolved from a common ancestor. The second cluster-binding region in P. aerogenes ferredoxin corresponds to the alpha-helix in B. thermoproteolyticus ferredoxin. The secondary-structure predictions strongly suggest that the alpha-helix is generally present in the monocluster-type ferredoxins. The conformational change to alpha-helix, insertions of a loop and a protrusion, as well as the absence of the second cluster in B. thermoproteolyticus ferredoxin, result in the lack of 2 fold symmetry present in P. aerogenes ferredoxin. So, the track of gene duplication is no longer detectable in the tertiary structure alone. The evolutionary events that may have occurred in the ferredoxins with the [4Fe-4S] cluster are discussed. PMID- 3351920 TI - Interaction between external medium and haem pocket in myoglobin probed by low temperature optical spectroscopy. AB - The visible absorption spectra of carbonmonoxymyoglobin in the temperature range 300 to 20 K are reported and compared with the analogous spectra of carbonomonoxyhaemoglobin. The temperature dependence of the zeroth, first and second moment of the observed bands is analysed to obtain information on the local dynamics in the proximity of the haem. Contrary to haemoglobin, the first moment of the observed bands in myoglobin is markedly affected by the solvent composition and its value saturates at temperatures at which the solvent undergoes the glass transition. These data indicate that solvent properties influence the haem pocket stereodynamics in myoglobin; moreover, the different behaviour between myoglobin and haemoglobin suggests that the process should involve the surfaces that are buried in the haemoglobin tetramer and exposed to the solvent in myoglobin, and/or the different protein compressibility. PMID- 3351919 TI - Protein-ligand dynamics. A 96 picosecond simulation of a myoglobin-xenon complex. AB - A 96 picosecond dynamics trajectory of myoglobin with five xenon-probe ligands in internal cavities is examined to study the effect of protein motions on ligand motion and internal cavity fluctuations. Average structural and energetic properties indicate that the simulation is well behaved. The average protein volume is similar to the volume of the X-ray model and the main-chain atom root mean-square deviation between the X-ray model and the average dynamical structure is 1.25 A. The protein volume oscillates 3 to 4% around the volume of the X-ray structure. These fluctuations lead to changes in the internal free volume and in the size, shape and location of atom-sized cavity features. Transient cavities produced in the simulation have a crucial role in the movement of two of the ligands. One of the ligands escapes to the protein surface, whilst a second ligand travels through the protein interior. Complex gating processes involving several protein residues are responsible for producing the necessary pores through which the ligand passes between transient cavities or packing defects. PMID- 3351921 TI - Two calmodulin genes are expressed in Arbacia punctulata. An ancient gene duplication is indicated. AB - Calmodulin is highly conserved, and only in the sea urchin Arbacia punctulata have two distinct isotypes been reported. We have isolated and sequenced two cDNAs from a lambda gt 11 library constructed from RNA from ovary tissue of A. punctulata. One clone, designated alpha, encodes a calmodulin isotype previously designated A. It encodes an amino acid sequence that is identical with calmodulin of most vertebrates in positions 1 through 141; however, it does not encode the last seven amino acids. The other clone, designated beta, starts with an open reading frame and encodes the B form of calmodulin from position 11 through the C terminal position 148. It has only four differences from vertebrate calmodulin, occurring at positions 78 (Asp, beta Glu), 99 (Tyr, beta Phe), 143 (Gln, beta Ala) and 147 (Ala, beta Ser). The nucleic acid sequences of the alpha and beta cDNAs differ at 46 nucleotide positions that are distributed throughout their coding sequences. We conclude that the corresponding mRNAs are not derived from post-transcriptional processing of a single gene, and we infer that they are transcribed from two non-allelic genes. The gene duplication is inferred to have occurred prior to the divergence of the vertebrates and the echinoderms. The expression of these calmodulin mRNAs in ovary tissue and eggs of a single animal differs as judged by hybridization of probes to RNA immobilized to filters. PMID- 3351922 TI - The human VK locus. Characterization of a duplicated region encoding 28 different immunoglobulin genes. AB - Two large regions of the human multigene family coding for the variable parts of the immunoglobulin light chains of the K type (VK) have been characterized on cosmid clones. The two germline regions, called Aa and Ab, span together 250,000 base-pairs and comprise 28 different VK gene segments, nine of which have been sequenced. There is a preponderance of VKII genes but genes belonging to subgroups I and III, and genes that cannot be easily assigned to one of the known subgroups, are interspersed within the VKII gene clusters. A number of pseudogenes have been identified. Within the Aa and Ab regions, all gene segments are organized in the same transcriptional orientation. The regions Aa and Ab, whose restriction maps are highly homologous, were shown not to be allelic structures; they must have arisen by a duplication event. Taken together with previous results, one can conclude that the major part of the VK locus exists in duplicated form. One individual has been found who has only one copy of some of the duplicated regions. By chromosomal walking, the A regions could be linked to the O regions, an analysis of which has been reported. The A regions contribute about one-third of the VK genes so far identified. PMID- 3351923 TI - Sequence and spacing requirements of a retrovirus integration site. AB - Following infection, retroviruses insert a DNA copy of their RNA genome into the host cell genome. This integrative recombination reaction occurs at specific sites on the viral DNA: inverted repeat sequences near the termini of the linear DNA form of the viral genome. We have described elsewhere the generation and analysis of deletion mutations at one of the inverted repeat sequences in Moloney murine leukemia virus. We describe here the effects of insertion mutations made at this locus. Our results show that substantial sequence changes at the site of recombination can be tolerated, and that the spacing between the cleavage sites on the viral DNA can be expanded as well as contracted while still allowing efficient viral integration. After several rounds of virus replication, each of the insertion mutants gave rise to pseudorevertants with new alterations at the integration site. PMID- 3351924 TI - A promoter of the rat insulin-like growth factor II gene consists of minimal control elements. AB - We have characterized the cis-control signals in one of the two promoters of the developmentally regulated rat insulin-like growth factor II gene (rIGF-II) by a combination of in-vivo transient expression, in-vitro transcription, footprinting, gel band-shifting and methylation-interference experiments, using a series of deletion mutant templates. Our results indicate that this simple (minimal) promoter (P2) consists of no more than 128 base-pairs, which include an ATA box and four proximal upstream GC boxes binding the general transcription factor Sp1. Three of the latter sites deviate from the known Sp1 consensus recognition sequence. The two types of cis-acting regulatory signals (GC/ATA motif) of the P2 promoter are inter-dependent and sufficient for transcription. A model for the operation of this type of minimal promoter is discussed. S1 nuclease-hypersensitive sites, localized by in-vitro mapping to the region of the P2 Sp1-binding sites, are also present in vivo and correlate with the transcriptional state of chromatin in the rIGF-II locus. We show that recognition sites for Sp1 binding are a subset of sequences that exhibit hypersensitivity to S1. PMID- 3351925 TI - Newly synthesized small nuclear RNAs appear transiently in the cytoplasm. AB - Newly synthesized small nuclear RNA (snRNA) species U1 and U2 are easily identified in cytoplasmic fractions prepared by standard aqueous cell fractionation. However, because the mature stable snRNA species leak from isolated nuclei during cell fractionation, the possibility exists that these newly synthesized species also leak from the nucleus. To overcome the problems of nuclear leakage, mouse L929 cells were fractionated by cell enucleation. Enucleation extrudes the nuclei from cytochalasin-treated cells and produces cytoplasts that, by several criteria, are a bona fide cytoplasmic fraction uncontaminated by nuclear material. All six of the major snRNAs are present in the cytoplasts (c-snRNAs) shortly after synthesis. The species are identified by immunoprecipitation with specific antisera against the ribonucleoproteins and by Northern blotting and hybrid selection using cloned probes. This confirms and extends similar studies that used non-aqueous cell fractionation and manual dissection to overcome nuclear leakage. Kinetic studies demonstrate that the c snRNAs return to the interphase nucleus after approximately 20 minutes in the cytoplasm. The U2 precursor U2' is processed to mature-sized U2 in the cytoplast fractions before returning to the nucleus. The c-snRNAs occur in ribonucleoprotein particles with similar antigenicity to the mature nuclear particles within six minutes of transcription. This suggests that in mammalian cells, important steps in the assembly of these ribonucleoproteins occur in the cytoplasm. PMID- 3351926 TI - Structural analysis of polymers of sickle cell hemoglobin. I. Sickle hemoglobin fibers. AB - The structure of fibers of deoxyhemoglobin S has been under investigation for several years and a number of different models have been proposed for the arrangement of molecules within the particles. We have used reconstruction and modeling techniques in our analysis of these structures. Several new approaches have been employed in this analysis in order to provide improved estimates of the co-ordinates, pairing, and polarity of the hemoglobin S molecules. Fibers have a variable pitch and, in order to minimize distortions in the reconstructed density maps associated with these variations in pitch, we have developed an iterative procedure to measure the instantaneous pitch and have modified the reconstruction algorithm to incorporate the measured values. This procedure improves the accuracy with which the hemoglobin S molecules can be located in the density maps. Furthermore, the determination of the instantaneous pitch allows us to measure directly the rotation of the individual hemoglobin molecules. These measurements are in excellent agreement with the values predicted using a random angular walk model (as originally proposed for F-actin) to describe the variable pitch. The reconstructions confirm that the fiber consists of 14 strands of hemoglobin S arranged in a hexagonally shaped cross-section. We have determined the pairing of the molecules to form double strands directly from the density maps by identifying the molecules that have intermolecular distances that conform to those of double strands in the Wishner-Love crystal. The seven double strands identified in this manner are consistent with the strand pairings proposed by Dykes et al. (1979) rather than the alternate pairings proposed by Rosen & Magdoff-Fairchild (1985). In addition, we have for the first time determined the polarity of the double strands directly from the reconstruction data. This was achieved using a procedure that amounts to essentially "dissecting" individual double strands from the reconstructed density maps so that their density distribution could be examined independently of the neighboring double strands. Knowledge of the relative polarities of the double strands is essential for determining the intermolecular interactions that stabilize the fiber. PMID- 3351927 TI - Structural analysis of polymers of sickle cell hemoglobin. II. Sickle hemoglobin macrofibers. AB - Sickle cell hemoglobin macrofibers are an important intermediate in the low pH crystallization pathway of deoxygenated hemoglobin S that link the fiber to the crystal. Macrofibers are a class of helical particles differing primarily in their diameters but are related by a common packing of their constituent subunits. We have performed three-dimensional reconstructions of three types of macrofibers. These reconstructions show that macrofibers are composed of rows of Wishner-Love double strands in an arrangement similar to that in the crystal. We have measured the orientation and co-ordinates of double strands in macrofibers using cross-correlation techniques. In this approach, the electron density projections of double strands calculated from the known high-resolution crystal structure are compared with regions along the length of the particles in which the distinct pattern of double strands in c-axis projection may be observed. Contrary to assertions by Makinen & Sigountos (1984), our results unambigously demonstrate that adjacent rows of double strands in macrofibers are oriented in an antiparallel manner, as in the Wishner-Love crystal. Adjacent rows of antiparallel double strands are displaced along the helical axis relative to their co-ordinates in the crystal. Electron density models of macrofibers based on the crystallographic structure of the sickle hemoglobin double strand are in good agreement with the projections of macrofibers observed in electron micrographs. We have studied the structure of a closely related crystallization intermediate, the sickle hemoglobin paracrystal. The arrangement of double strands in paracrystals is similar to that in Wishner-Love crystals, except that they are displaced along the a-axis of the crystal. Measurements of the double strand co-ordinates reveal that the distribution of strand positions is bimodal. These results further establish the close structural relationship between macrofibers and paracrystals as intermediates in the crystallization of deoxygenated sickle hemoglobin. PMID- 3351929 TI - Control of gene expression in the P2-related temperate coliphages. V. The use of sequence analysis of 186 Vir mutants to indicate presumptive repressor binding sites. AB - The prophage of coliphage 186 produces a repressor protein that is required for maintenance of lysogeny and that renders lysogenic cells immune to superinfection by 186. The repressor is likely to be a DNA-binding protein that prevents transcription of the 186 early-lytic genes from promoter pR. To identify the binding site of the repressor, we have isolated virulent mutants that are able to form plaques in the presence of repressor and determined their DNA sequences around pR. The mutants all have mutations in an inverted repeat within pR, and we predict that this repeat is the primary binding site of the repressor. Many of the mutants have second mutations near pR, which allow them to form plaques in the presence of higher concentrations of repressor. The sequences containing these "secondary" mutations show no homology with the putative repressor-binding site, and the role of these mutations in virulence is not clear. PMID- 3351928 TI - Local mobility of nucleic acids as determined from crystallographic data. III. A daunomycin-DNA complex. AB - The local mobility of the complex between the anti-tumor drug daunomycin and a DNA hexanucleotide duplex of sequence d(CpGpTpApCpG)2 has been determined by anisotropic refinement of single crystal X-ray diffraction data of 1.2 A resolution (1 A = 0.1 nm). The directions and amplitudes of the local motion indicate that changes in mobility of DNA due to daunomycin binding are primarily limited to the residues forming the intercalation site and do not propagate to the neighboring residues. The intercalated daunomycin ring system (aglycone) is rigidly fixed in the base stack, apparently serving as an anchor for the amino sugar segment of the drug which is one of the most mobile regions of the entire complex. The high flexibility of this amino sugar may be important for inhibition of replication and transcription not only by sterically blocking the minor groove, but also by allowing nonproductive interactions to be formed with various polymerases or other DNA-binding proteins. The crystallographic model is improved sufficiently by the rigid group anisotropic refinement to allow additional bound water molecules to be located. PMID- 3351930 TI - Structural analysis of polymers of sickle cell hemoglobin. III. Fibers within fascicles. AB - We have examined the structure of hemoglobin S fibers, which are associated into large bundles, or fascicles. Electron micrographs of embedded and cross-sectioned fascicles provide an end-on view of the component fibers. The cross-sectional images are rotationally blurred as a result of the twist of the fiber within the finite thickness of the section. We have applied restoration techniques to recover a deblurred image of the fiber. The first step in this procedure involved correlation averaging images of cross-sections of individual fibers in order to improve the signal-to-noise ratio. The rotationally blurred image was then geometrically transformed to polar co-ordinates. In this space, the rotational blur is transformed into a linear blur. The linearly blurred image is the convolution of the unblurred image and a point spread function that can be closely approximated by a square pulse. Deconvolution in Fourier space, followed by remapping to Cartesian co-ordinates, produced a deblurred image of the original micrograph. The deblurred images indicate that the fiber is comprised of 14 strands of hemoglobin S. This result provides confirmation of the fiber structure determined using helical reconstruction techniques and indicates that the association of fibers into ordered arrays does not alter their molecular structure. PMID- 3351931 TI - Structure of tumour necrosis factor by X-ray solution scattering and preliminary studies by single crystal X-ray diffraction. AB - The structure of tumour necrosis factor has been investigated by X-ray small angle scattering and X-ray diffraction using synchrotron radiation. The overall radius of gyration is 25.5 A. A plausible model accounting for the scattering curves consists of an elongated trimer with an axial ratio of 3 to 4 and a maximal chord with a lower limit of 80 A. Tumour necrosis factor has been crystallized in a trigonal space group. Our results are in favour of a single trimer in the asymmetric unit. The diffraction extends to 3.5 A. PMID- 3351932 TI - Crystallization and preliminary crystallographic data for oncomodulin. PMID- 3351933 TI - Crystallization and preliminary X-ray study of staphylococcal enterotoxin B. PMID- 3351934 TI - Molecular cloning and sequence of the concatemer junction from vaccinia virus replicative DNA. Viral nuclease cleavage sites in cruciform structures. AB - The concatemer junction from replicative forms of vaccinia virus DNA was cloned into plasmid vectors and shown to be a precise duplex copy of the viral terminal hairpin structure, with each strand corresponding to one of the alternative sequence isomers. The plasmids were relaxed circles with extruded cruciforms representing two copies of the vaccinia telomere hairpin structure. Head-to-head dimers containing two copies of the vaccinia virus concatemer junction were observed to contain only one set of stem-loop structures per molecule, suggesting that the initial formation of a small cruciform, and not branch migration, was the rate-limiting step in cruciform formation. The plasmids containing the concatemer junction were converted into nicked circular, linear and cross-linked linear molecules by a nuclease isolated from vaccinia virions. The region specific cleavage near the border of the hairpin loop and the formation of DNA cross-links in some of the molecules is consistent with the nuclease acting as a nicking-closing enzyme that participates in the resolution of mature termini from replicative concatemer intermediates. PMID- 3351935 TI - Characterization of the gene encoding ovine beta-lactoglobulin. Similarity to the genes for retinol binding protein and other secretory proteins. AB - Beta-lactoglobulin is the major whey protein in the milk of ruminants and is expressed in the mammary gland during pregnancy and lactation. Here we describe the isolation and characterization of genomic clones encoding ovine beta lactoglobulin. Two very similar but non-identical, types of beta-lactoglobulin clone were obtained. DNA sequence analysis of one of these showed that the gene is 4900 bases long and contains seven exons. It codes for a protein of 180 amino acid residues, containing an 18-residue signal peptide, within exons I to VI; exon VII is non-coding. We show that the genes encoding serum retinol binding protein, major urinary protein, alpha-1-acid glycoprotein and apolipoprotein D have a similar organization of exons and introns to beta-lactoglobulin. In particular, a comparison between beta-lactoglobulin and retinol binding protein shows that both genes encode equivalent elements of three-dimensional protein structure within analogous exons. These proteins are all members of a large, diverse family of secretory proteins, many of which function in binding small hydrophobic molecules. PMID- 3351936 TI - Structure and evolution of the horse zeta globin locus. AB - The equine zeta globin gene locus consists of an intact 5' gene and a truncated 3' pseudogene (psi zeta) that has only 5' control sequences and a first exon and intron. Nevertheless, the psi zeta gene has retained almost perfect homology with its neighbour, presumably by gene conversion. The first introns of both zeta and psi zeta genes contain a number of degenerate tandem repeats of a 14 base-pair sequence that has been found in the zeta genes of goats and humans and that is related to a family of human minisatellite sequences. Comparisons of sequences flanking the zeta and psi zeta genes reveal areas of considerable interspecies homology, which can be explained by a zeta gene duplication that pre-dated the mammalian radiation. PMID- 3351937 TI - Sequence of chicken c beta 7 tubulin. Analysis of a complete set of vertebrate beta-tubulin isotypes. AB - In chicken, beta-tubulin is encoded by a family of seven genes. We have now isolated and sequenced overlapping cDNA clones corresponding to gene c beta 7 (previously designated c beta 4'), the only chicken beta-tubulin not previously characterized. The inferred amino acid sequence of c beta 7 tubulin is identical with the class I beta-tubulin isotype found in human, mouse and rat. Moreover, c beta 7 is highly expressed in almost all tissue and cell types in chicken, a pattern similar to those of the genes for class I beta-tubulin isotypes in other vertebrates. Comparison of the complete family of chicken beta-tubulin gene sequences reveals that the heterogeneity of beta-tubulin polypeptides encoded in a higher eukaryote is confined to six distinct beta-tubulin isotypes. Five of these are members of evolutionarily conserved isotypic classes (I to V), whereas the sixth represents a divergent erythroid-specific tubulin whose sequence has not been conserved. PMID- 3351938 TI - Rat lens gamma-crystallins. Characterization of the six gene products and their spatial and temporal distribution resulting from differential synthesis. AB - We have isolated, purified and characterized six individual gamma-crystallin polypeptides present in the rat lens. Comparison of their amino acid compositions with the known structure of the six gamma-crystallin genes permits a one-to-one correspondence to be made between each protein synthesized and the encoding gene. This demonstrates that each of the six genes is actually expressed in vivo. Two classes of three gamma-crystallins each, which we have designated classes gamma ABC and gamma DEF, are known to exist, on the basis of internal sequence homology. We have measured the temperature-dependent phase-separation characteristics of solutions of the six purified gamma-crystallins, and find that the three members of the gamma DEF class (gamma 2-2, gamma 3-1 and gamma 4-1) are all cryo-proteins with relatively high phase-separation temperatures, whereas the three gamma ABC crystallins (gamma 1-1, gamma 1-2 and gamma 2-1) do not show phase separation above -7 degrees C. We have measured the spatial distribution in rat lens of each of the alpha-, beta- and gamma-crystallins as a function of age from 1 to 420 days, using size-exclusion and ion-exchange high-pressure liquid chromatography (HPLC). Our findings in the cortical layer permit us to establish the differential synthesis of each of the crystallins during lens development. Particular attention has been devoted to the spatial and temporal distribution of the six individual gamma-crystallins. Up to birth, synthesis of the three components of the gamma DEF class predominates, and in particular that of gamma 2 2. In subsequent development the three components of the gamma ABC class assume a greater proportion of monomeric crystallins synthesized, while beta s-crystallin synthesis predominates in late development. Our analysis of different layers within single lenses provides novel information on spatial gradients of the water soluble and water-insoluble protein fractions as a function of age. We consider the consequences of these findings for lens transparency and opacity in both rat and mouse lens. We show that the high concentrations of gamma DEF-crystallins appear to be responsible for the opacity known to occur in young rat lenses. We conclude from these observations that close control of the differential synthesis of gamma-crystallins plays an important role in maintaining lens transparency during development. PMID- 3351939 TI - Recurring loop motif in proteins that occurs in right-handed and left-handed forms. Its relationship with alpha-helices and beta-bulge loops. AB - A common feature of alpha-helices in proteins is a loop at the C-terminal end, with a characteristic hydrogen bond pattern. It is noted that several loops with the same structural features occur independently of alpha-helices; two are even situated at the loop ends of beta-hairpins. The name paperclip is suggested for loops possessing the appropriate hydrogen bonds. A number of features of paperclips are described: they exist in two classes, depending on the number of residues at the loop end; one class is very much commoner than the other. Two paperclips are found that belong to the common class, except that the main-chain conformation of each is the mirror image of that normally found. The majority of paperclips are shown to have tightly clustered sets of main-chain dihedral angles. These are somewhat similar to, but distinct from, a subgroup of another common family of loops that have been called beta-bulge loops; in the latter, the dihedral angles are also tightly clustered. The high degree of clustering in both cases is likely to be a result of steric constraints associated with hydrogen bond patterns at the ends of loops. PMID- 3351940 TI - Calculations on crystal packing of a flexible molecule, Leu-enkephalin. AB - Crystal packing calculations have been carried out on a substantial number of conformations of Leu-enkephalin; namely, those obtained both from crystal structures and from energy minimizations on isolated molecules, and with and without waters of crystallization. The known crystal structures represent the most energetically stable packings found. The conformations of the enkephalin molecules in the crystal are not the most stable for an isolated molecule; i.e. intermolecular interactions force the isolated molecule to change conformation in order to achieve a small packing volume and an optimal packing energy in the crystal. It is found that the packing energy of an enkephalin molecule is a reasonably smooth function of its molecular volume in the unit cell, if structures with intermolecular hydrogen bonding are excluded, and is substantially independent of other details of the molecular conformation or of the crystal packing. Hydrogen bonding provides additional stabilization of the crystal structure, and would likely permit crystallization of the system if it is sufficiently dense. Solvent molecules further stabilize the structure when they can also provide intermolecular hydrogen bonds. PMID- 3351941 TI - Fluctuations in the polymerization of sickle hemoglobin. A simple analytic model. AB - Using the stochastic theory of chemical reactions and the theory of first passage times, a simple analytic expression is derived for the distribution of delay times that has been observed in studies of the polymerization kinetics of sickle hemoglobin under conditions where the polymerization progress curves exhibit stochastic variation. The rate of homogeneous nucleation can be readily extracted from such experiments using this expression. This work constitutes a significant addition to the rather limited number of examples where contact can be successfully made between the stochastic theory of chemical kinetics and experiment. PMID- 3351942 TI - Preliminary X-ray crystallographic study of amicyanin from Thiobacillus versutus. PMID- 3351943 TI - Nucleotide sequence analysis of soybean small heat shock protein genes belonging to two different multigene families. AB - In soybean, the small heat shock proteins of 15 to 18 kDa are encoded in the nucleus by at least two different multigene families, designated class I and class VI. Genomic DNA sequences of two new heat shock genes and flanking regions were determined: Gmhsp18.5-C, a class I gene, and Gmhsp17.9-D, the first known class VI gene. Comparison of both genes revealed a moderate homology (approx. 38%) mainly within the 3' ends of their coding regions. Hydropathic characterizations and secondary-structure predictions of the deduced amino acid sequences revealed two conserved domains within the C-terminal halves of the polypeptides that are also present in related proteins of other organisms. The transcription of both genes is heat shock dependent and the mRNA start sites, as determined by S1 nuclease mapping, are located downstream from typical TATA box sequences and multiple heat shock promoter elements such as 5' CT-GAA--TTC-AG. The putative promoter regions of the genes are preceded by long tracts of repetitive sequences with a high A + T content of 79 to 89%, which are bordered by runs of "simple sequences" such as (A) 12/13, (T)10 and (TA)10. Similar characteristic features are present in the promoter and 5'-flanking regions of other soybean heat shock genes. The possible function of these distinct sequences is discussed. PMID- 3351944 TI - 5' structural motifs and Xenopus beta globin gene activation. AB - We have analysed the structure of the Xenopus beta globin gene 5' flanking region in erythroid and non-erythroid chromatin, in supercoiled plasmids and in minichromosomes assembled in HeLa cell transfections. We have identified two erythroid chromatin-specific, nuclease-hypersensitive sites (HSs), one centred on the cap site, the other located 1000 base-pairs further upstream. An (AT)n tract is located 200 base-pairs upstream from each of these sites. In supercoiled plasmids, the (AT)n tracts, and not the chromatin HSs, are preferentially cleaved by single strand and double strand-specific nucleases. Using restriction enzymes, we have looked at the structure of the cap site HS in minichromosomes assembled in HeLa cell transfections. We find that the structure is indistinguishable from that found in erythroid chromatin, thus reinforcing our previous suggestion, based only on DNase I studies, that the formation of this HS is not dependent on erythroid-specific factors. In view of this close structural mimicry of the situation in vivo, we have used the HeLa cell model system to study the sequences required for cap site HS formation. We find that deletion of the (AT)n tract immediately upstream influenced neither the formation of the HS nor transcription of the globin gene. Indeed, these features remained unaffected by further deletion of upstream sequences, including 50 base-pairs of the HS itself. In this construct, the dimensions of the HS remained the same as in the undeleted construct, with the plasmid sequences that replaced the deleted Xenopus sequences becoming hypersensitive. Thus, HS formation is directed by sequences downstream from --116 acting over a distance of at least 50 base-pairs. PMID- 3351945 TI - Crystal structure of p-hydroxybenzoate hydroxylase complexed with its reaction product 3,4-dihydroxybenzoate. AB - Crystals of the flavin-containing enzyme p-hydroxybenzoate hydroxylase (PHBHase) complexed with its reaction product were investigated in order to obtain insight into the catalytic cycle of this enzyme involving two substrates and two cofactors. PHBHase was crystallized initially with its substrate, p hydroxybenzoate and the substrate was then converted into the product 3,4 dihydroxybenzoate by allowing the catalytic reaction to proceed in the crystals. In addition, crystals were soaked in mother liquor containing a high concentration of this product. Data up to 2.3 A (1 A = 0.1 nm) were collected by the oscillation method and the structure of the enzyme product complex was refined by alternate restrained least-squares procedures and model building by computer graphics techniques. A total of 273 solvent molecules could be located, four of them being presumably sulfate ions. The R-factor for 14,339 reflections between 6.0 A and 2.3 A is 19.3%. The 3-hydroxyl group of the product introduced by the enzyme is clearly visible in the electron density, showing unambiguously which carbon atom of the substrate is hydroxylated. A clear picture of the hydroxylation site is obtained. The plane of the product is rotated 21 degrees with respect to the plane of the substrate in the current model of enzyme substrate complex. The 4-hydroxyl group of the product is hydrogen bonded to the hydroxyl group of Tyr201, its carboxyl group is interacting with the side-chains of Tyr222, Arg214 and Ser212, while the newly introduced 3-hydroxyl group makes a hydrogen bond with the backbone carbonyl oxygen of Pro293. PMID- 3351946 TI - Crystal structure of manganese superoxide dismutase from Bacillus stearothermophilus at 2.4 A resolution. AB - The crystal structure of manganese superoxide dismutase (MnSOD) from Bacillus stearothermophilus has been solved at 2.4 A resolution by a combination of multiple isomorphous replacement and molecular replacement (1 A = 0.1 nm). The structure has been refined to a conventional R-factor for all 16,560 unique reflections at 2.4 A of 0.26, and the 2Fo-Fc density maps show features more consistent with the known amino acid sequence of MnSOD from B. stearothermophilus than with the starting model, the MnSOD from Thermus thermophilus. The molecule is a dimer of identical subunits, each with 203 amino acid residues. The polypeptide chain of the monomer is organized into two domains, one of which has an "all-alpha" structure and the other an "alpha/beta" structure, with the manganese ion bound between them. The ion is co-ordinated by three histidine residues, 26, 81 and 167, and one aspartic acid residue, 173, in a tetrahedral arrangement strongly distorted towards trigonal pyramidal. We anticipate that Tyr34, whose hydroxyl group is only 5 A from the metal, is involved in the catalytic reaction. The active site is particularly rich in aromatic amino acid residues. As in the Cu/ZnSOD there are indications that MnSOD provides electrostatic guidance to the substrate entering the active site. PMID- 3351947 TI - Morphological and videofluorographic study of the hyoid apparatus and its function in the rabbit (Oryctolagus cuniculus). AB - The anatomy of the hyoid apparatus and positional changes of the hyoid bone during mastication and deglutition are described in the New Zealand White rabbit (Oryctolagus cuniculus). A testable model is constructed to predict the range of movement during function of the hyoid, a bone entirely suspended by soft tissue. Frame-by-frame analysis of a videofluorographic tape confirms the accuracy of the prediction through observation of hyoid bone excursion during oral behavior. During chewing, translation of the hyoid bone is diminutive and irregular, lacking a clearly discernible path of excursion. However, some movements of the hyoid occur with regularity. During fast opening, anterodorsal movement of the hyoid is interrupted with an abrupt posteroventral depression when the bolus is moved posteriorly toward the cheek teeth by the tongue. This clockwise rotation (when viewed from the right side) of the hyoid accompanies jaw opening and is reversed (posteroventral movement) for the jaw closing sequence. Lateral movements of the hyoid may be slightly coupled to mandibular rotation in the horizontal plane. The findings suggest that the hyoid bone maintains a relatively static position during the dynamics of chewing. The primary function would be to provide a stable base for the movements of the tongue. Another possible function would be to control the position of the larynx within the pharyngeal cavity. Some characteristic features of the rabbit hyoid apparatus may be consequential to relatively erect posture and a saltatory mode of locomotion. PMID- 3351948 TI - Morphology of the pronephros of the juvenile brown trout, Salmo trutta. AB - The pronephros in juvenile brown trout (Salmo trutta) consists of a large ovoid renal corpuscle and a pair of tubules. The corpuscle is retained for 11 months, after which the glomerulus regresses. The glomerular arteries come directly from the dorsal aorta. The interstitium is permeated with venous blood vessels that arise from the anterior cardinal veins and are closely apposed to the tubules. Two distinct segments of the pronephric tubular system are distinguished by the histological and ultrastructural features of their component cells: 1) a short, transitional neck in which cells change from capsular epithelium to columnar epithelium, typical of tubules; 2) the convoluted segment composed of cells similar to first proximal tubular cells of the opisthonephros with well-formed brush borders, apical vesicles that vary in size and number along this segment, and lysosomes. Pinocytosis and exocytosis are also evident in this segment. The tubular system increases in length and in its convolutions until about week 9, when the opisthonephros develops. Distally each tubule connects with a Wolffian duct, with cells marked by the absence of apical inclusions and the presence of a uniform brush border, numerous mitochondria, and elaborate infolding of the basalar membrane. Nephrostomes, which are often characteristic of pronephroi, are not present. Cells with long cilia are found throughout the tubular system but are most characteristic of the neck and Wolffian-duct segments. PMID- 3351950 TI - Program and abstracts of the VIIth meeting (Japanese Section) of the International Society for Heart Research. Keidanren Kaiken, Japan, 12-13 February 1988. PMID- 3351951 TI - Patient teaching tools in the ophthalmic unit. PMID- 3351949 TI - A quantitative analysis of mitochondria during fetal mouse oogenesis. AB - A quantitative analysis of mitochondrial populations during the meiotic prophase of mouse oogenesis was carried out. The mean absolute area occupied by mitochondria and the mean number of mitochondria per cell increases in a linear fashion from pachytene through dictyate. The mean area occupied by mitochondria increases at pachytene and thereafter. Both small and large aggregations of mitochondria are seen, particularly during the later stages of prophase. Vacuolated mitochondria are present from preleptotene through pachytene. Mitochondria show major dynamic changes throughout fetal mouse oogenesis, which may suggest significant functional activities yet to be elucidated. PMID- 3351952 TI - Essentials of writing for publication. PMID- 3351953 TI - Use of the Honan intraocular pressure reducer. PMID- 3351955 TI - A surgical counseling plan for patients undergoing cataract surgery. PMID- 3351954 TI - ECCE with phacoemulsification and flexible IOL implantation. PMID- 3351956 TI - Evaluating a choroidal mass. PMID- 3351958 TI - New treatment for invasive bladder cancer: early results. PMID- 3351957 TI - Natural products as antitumor agents: direct versus indirect mechanisms of activity of flavonoids. PMID- 3351959 TI - Screening tests: wasteland or proving ground? PMID- 3351960 TI - Effect of flavone acetic acid on Lewis lung carcinoma: evidence for an indirect effect. AB - Flavone-8-acetic acid (FAA), a new antitumor agent currently undergoing clinical trial, fails to inhibit the growth of early stage Lewis lung (LL) tumors growing in the lung. However, the growth of advanced subcutaneous tumors, arising from inoculation of either the original in vivo LL line or a tissue culture-adapted cell line (LLTC) derived from the LL line was delayed significantly by FAA treatment. Comparison, by clonogenic survival assays, of the cytotoxic effect of FAA on LLTC cells demonstrated that most cell killing occurred between 2 and 8 hours following in vivo exposure but occurred to a much lesser extent and at later times following in vitro exposure. FAA was inactive against LLTC cells growing in vivo in diffusion chambers, suggesting that a host cellular component was necessary for activity. FAA was found to induce hemorrhagic necrosis in the advanced LL tumors, as well as in a number of human tumor xenografts growing in athymic mice. The human cell lines from which the xenografts were derived, as well as the LL tumor lines and P388 leukemia lines, were inhibited by FAA in vitro. However, the ranking of FAA activity in vivo did not parallel that observed in vitro. Together, these observations strongly suggest that FAA has an indirect mode of antitumor action. PMID- 3351961 TI - Differential effect of dietary methionine on the biopotency of selenomethionine and selenite in cancer chemoprevention. AB - The influence of a low methionine intake on the chemopreventive efficacy of selenomethionine versus selenite was compared in the 7,12 dimethylbenz[a]anthracene-induced mammary tumor model in rats. Animals were fed from weaning a purified 20% casein diet with or without 0.3% methionine supplementation. Selenomethionine or selenite, at a final concentration of 3 ppm of selenium (Se), was added to the diet starting 5 days after DMBA administration. Control rats continued to receive the basal diets which contained 0.1 ppm of Se. Results of the carcinogenesis experiment indicated that suboptimal dietary methionine significantly reduced the protective effect of selenomethionine in cancer prevention. In contrast, the efficacy of selenite was not affected. In rats given 3 ppm of selenomethionine, tissue Se was actually higher in those fed a diet with a suboptimal amount of methionine than in those with an adequate intake of methionine. On the other hand, dietary methionine did not influence the level of tissue Se in animals given selenite. An increase of dietary methionine to 0.6% did not enhance the efficacy of selenomethionine in cancer protection but would allow the use of a higher level of selenite without the accompanying adverse effects. The biological significance of Se utilization under suboptimal or adequate methionine intake was also assessed using the glutathione peroxidase assay in the liver of Se-deficient rats given graded levels of Se as either selenite or selenomethionine. The enzyme study demonstrated that low dietary methionine decreased the nutritional biopotency of selenomethionine in restoring glutathione peroxidase activity but not that of selenite. These experiments suggest that adequate methionine intake is required for the utilization of selenomethionine for nutritional and anticarcinogenic purposes. PMID- 3351962 TI - Flat adenomas in a colon cancer-prone kindred. AB - We describe new pathologic findings in a hereditary nonpolyposis colorectal cancer family. Affected family members developed multiple small adenomas with right-sided predominance; many adenomas had an unusual appearance featuring slightly elevated lesions with adenomatous changes confined to the upper regions of the colonic crypts. We have adopted the previously established term "flat adenoma" for these lesions. This phenotype may be a morphologic marker for at least one subset of hereditary nonpolyposis colorectal cancer. PMID- 3351963 TI - Muscle electrophysiology in patients with advanced breast cancer. AB - Sixty-one consecutive patients with advanced breast cancer (defined as metastatic disease) and 20 normal age- and sex-matched controls were admitted to a prospective study designed to assess muscle electrophysiology. Nutritional status, lean body mass, and ultrasonographic measurement of the triceps brachialis, sternomastoid, and adductor pollicis muscles were determined in patients and controls. In addition, tumor mass and performance status were determined in the patient group. Electrophysiology of the adductor pollicis muscle was assessed during isometric voluntary maximum effort and during electrical stimulation via the ulnar nerve (80-120 V, 50-100 msec). Nutritional status, lean body mass, and ultrasonographic measurements of the triceps brachialis, sternomastoid, and adductor pollicis were not significantly different between patients and controls. Maximum strength after supramaximal stimulation at 50 Hz was 34 +/- 15 N in patients, versus 40 +/- 9 (P less than .01) N in controls. Relaxation velocity was 336 +/- 149 N/sec in patients, versus 507 +/- 251 (P = .02) N/sec in controls. Fatigue (% of initial strength after 30 sec of stimulation) was 67% +/- 22% in patients, versus 79% +/- 17% (P = .03) in controls. Muscle electrophysiology did not correlate with tumor mass or performance status. It was concluded that patients with advanced breast cancer have abnormal muscle electrophysiology that is not due to abnormal nutritional status or decreased muscle mass. More research is needed to better characterize this disorder and to better define its cause. PMID- 3351964 TI - Risk of hepatobiliary cancer in carriers of Salmonella typhi. PMID- 3351965 TI - Trends in cervical cancer rates in Norway. PMID- 3351966 TI - Being black in America is hazardous to your health. PMID- 3351967 TI - Origin of AIDS. PMID- 3351968 TI - The University of Florida sickle cell screening program for neonates: design and results. AB - During the first 18 months of a pilot program for sickle cell screening at the University of Florida College of Medicine, Gainesville, 2,058 black neonates were screened. An incidence of homozygous sickle disease of 0.5 percent was greater than that expected or predicted by carrier frequency (8.3 percent). Fifty percent of all infants with abnormal cord blood electrophoreses were retested. All infants with actual homozygous disease or other clinically significant variants had confirmation of their diagnosis and were channeled for appropriate care. A change of phenotypic diagnosis based on a follow-up sample was made in eight cases. Errors were either interpretational or through contamination of cord blood samples by maternal blood at the time of delivery. Although location of infants for retesting after discharge was made more difficult by the largely rural composition of the target population, certain measures were taken to improve patient retrieval: use of public health personnel; enlistment of the aid of private physicians in the community; and inclusion of information regarding the screening program in the hospital discharge packets of black mothers. It is concluded that screening programs serving rural populations can adequately identify infants with abnormal hemoglobin patterns while educating and caring for families of these infants in a cost-efficient and effective manner. PMID- 3351969 TI - Representation of the black elderly in Detroit metropolitan nursing homes. AB - This paper presents the results of an analysis of the distribution of black elderly patients in the long-term care systems of Detroit City, Wayne, and Oakland counties, Michigan. These areas were chosen because of their proximity to Wayne State University and because Detroit has a large black population. Wayne and Oakland counties are largely suburban areas. Black, long-term care utilization was compared with the black elderly representation of the base population in these three locations. The sex-specific distribution between whites and blacks in long-term care populations revealed that black men utilized the greatest amount of long-term care and were more dependent on Medicaid. One hundred twenty-one licensed nursing homes were contacted by telephone and a follow-up questionnaire was sent to the respondents during the five-month study period.It has been observed nationally that the elderly black population is underrepresented in the long-term care system. The findings obtained in this study, however, are not in agreement with the national trend. In Detroit, the black elderly are represented in nursing homes in approximate proportion to their representation in the larger community.This analysis raises questions of need vs utilization of long-term care by the black elderly in urban areas. This is the first study of black elderly long-term care representation in a specific urban area in the United States. PMID- 3351971 TI - Bloodless operation for a giant hydrocele. AB - A new hydrocele eversion technique designed for treating giant hydroceles (fluid content over 3 L) is described. The technique takes advantage of the existence of an avascular, loose areolar plane between the external and internal spermatic fascia within which a subdartos-cremasteric pouch is developed. The hydrocele fluid is drained through a trochar and cannula, and the tunica vaginalis is everted and then quilted with 2/0 chromic catgut. The testis and the quilted tunica are placed in the subdartos-cremasteric pouch and the incision is closed. The quilting of the tunica vaginalis not only prevents reinversion of the sac, but, together with the tight fit of the pouch around the sac, it also reduces the potential space into which postoperative seroma can accumulate.This technique is particularly useful when fibrous adhesions develop between the tunica vaginalis and the subjacent spermatic fascia in giant hydroceles. No drains or external pressure dressing are required, and the technique has been used in 14 giant hydroceles with no complications or recurrence. PMID- 3351970 TI - The relationship of isolated sleep paralysis and panic disorder to hypertension. AB - An hypothesis is proposed that there exists a subgroup of African-American hypertensive patients whose hypertension could have been prevented by the early detection and treatment of easily recognizable symptoms that signal the initiation of the pathophysiologic processes that lead to essential hypertension.A pilot study of 31 patients with elevated blood pressure revealed that 41.9 percent had isolated sleep paralysis, 35.5 percent had panic attacks, and 9.7 percent had panic disorder. These proposed hyperadrenergic phenomena may be related to the development of hypertension in certain individuals. PMID- 3351972 TI - Sirenomelia: mermaid syndrome. AB - Sirenomelia, or "mermaid syndrome," represents a severe form of caudal regression. It is a rare congenital malformation that is incompatible with life. In the following case report, a double inferior vena cava was also present, and this anomaly in association with sirenomelia has not been reported. Ultrasound may be useful in the early antenatal detection of this anomaly. This is the first case of sirenomelia reported in the black race. PMID- 3351974 TI - Incisional recurrence of endometrial adenocarcinoma. AB - A 73-year-old woman manifested recurrent endometrial carcinoma, which presented as multiple nodular lesions in an abdominal scar from previous pelvic surgery. PMID- 3351973 TI - Epidural angiolipoma with spinal cord compression. AB - A case of epidural angiolipoma is reported. This tumor rarely occurs in the spinal canal. The most common location is in the thoracic region, and its histogenesis is probably congenital. PMID- 3351975 TI - Institutional imperatives: a clear message from the Association of American Medical Colleges. PMID- 3351976 TI - Time course of electrophysiologic effects induced by di-n-butyl-2,2-dichlorovinyl phosphate (DBCV) in the adult hen. AB - Previous work in our laboratory indicated that di-n-butyl-2,2-dichlorovinyl phosphate (DBCV) produced electrophysiologic changes in hen peripheral nerve that coincided with the development of histopathologic changes and neurologic signs of peripheral neuropathy. The purpose of the present study was to follow the time course for the development of the electrophysiologic changes and to determine whether pretreatment with the phosphinate analog of DBCV (DBCV-P), a nonageable organophosphorus compound, prevented these effects. Although significant electrophysiologic deficits occurred in the tibial and sciatic nerve 24 h after DBCV treatment, the most marked changes coincided with the onset of clinical signs of organophosphorus-induced delayed neuropathy (14-21 d). The sciatic and tibial nerves were equally susceptible to DBCV in producing deficits characterized by changes in the relative refractory period and an increased strength-duration threshold. Pretreatment with DBCV-P prevented the clinical signs and also attenuated the electrophysiologic deficits induced by DBCV treatment. These data suggest that electrophysiologic deficits occur before clinical signs of organophosphorus-induced delayed neuropathy (OPIDN) and may be indicative of a link between neurotoxic esterase (NTE) inhibition and onset of overt clinical toxicity. PMID- 3351977 TI - Hepatic changes in rats following subchronic administration of FYROL 6, an organophosphorus ester flame retardant. AB - This study conducted to evaluate the subchronic toxicity of FYROL 6 [diethyl N,N bis-(2-hydroxyethyl)aminomethylphosphonate] in rats demonstrated an hepatic effect not commonly reported for related compounds. Sprague-Dawley rats of both sexes were gavaged daily with 0, 10, 100, or 500 mg/kg FYROL 6 in corn oil for 13 wk. No treatment-related mortality and few signs of toxicity were noted during the study. Fyrol 6 did not inhibit plasma, erythrocyte, or brain cholinesterase activities. Treatment-related necropsy and microscopic alterations were restricted to the liver. Increased liver weights, hepatocellular hypertrophy, and eosinophilia of centrilobular hepatocytes were evident in 100-mg/kg females and in both sexes at 500 mg/kg. Morphometric analysis revealed a 40% increase in cross-sectional area of individual hepatocytes in 500-mg/kg males, compared to controls. There was no morphologic evidence of hepatic necrosis or clinical evidence of liver dysfunction. This study demonstrated low toxicity for FYROL 6 and treatment-related changes restricted to the liver suggestive of an adaptive response to FYROL 6. PMID- 3351978 TI - Body and organ weights of rats exposed to carbon monoxide at high altitude. AB - Although chronic exposure to carbon monoxide (CO) or high altitude produces pronounced cardiovascular changes in humans as well as animals, there is little information on the effects elicited by these stressors combined. Theoretical considerations, as well as data from acute studies, suggest that CO inhaled at high altitude may be more detrimental than CO inhaled at low altitude. The purpose of these studies was to construct a system in which CO and altitude could be controlled precisely, and to investigate the effects of continuous exposure to CO and high altitude on body weights and hematocrit ratios, as well as heart, spleen, adrenals, kidneys, and pituitary weights. Male, laboratory rats were exposed for 6 wk in steel barometric chambers to (1) 100 ppm CO, (2) 15,000 ft simulated high altitude (SHA), and (3) CO at SHA. Altitude was simulated by a system of gate valves and a vacuum pump, and measured by an altimeter. CO, from high-pressure cylinders, was introduced into the air supplying each chamber through a mass flow controller and measured by a nondispersive infrared (NDIR) analyzer. Although SHA had no affect on left ventricle plus septum (LV + S), adrenal, spleen, or kidney weights, SHA decreased body weights, and increased hematocrit ratios, as well as right ventricle (RV), total heart (HT), and pituitary weights. CO had no affect on body weights, RV, HT, adrenal, spleen, or kidney weights, but CO increased hematocrit ratios and LV + S weights. There was no significant interaction between SHA and CO on any parameter except kidney weight. These results indicate that, in general, the effects produced by 15,000 ft SHA are not intensified by exposure to 100 ppm CO. PMID- 3351979 TI - Impairment of calcium homeostasis by hexachlorobenzene (HCB) exposure in Fischer 344 rats. AB - Human exposure to hexachlorobenzene (HCB) has resulted in demineralization of bone and development of osteoporosis. Experiments were undertaken to investigate the effects of HCB on the homeostatic mechanism of calcium metabolism. Fischer 344 rats were dosed with 0, 0.1, 1.0, 10.0, or 25.0 mg HCB/kg body weight 5 d/wk for 5 wk while being fed normal rat diet or vitamin D3-deficient diet. Rats receiving the normal diet had a dose-related decrease in body weight gain and increased liver weight when compared to their controls. Serum cholesterol, alanine aminotransferase (ALT), 1, 25-dihydroxy-vitamin D3 [1,25-(OH)2D3], and parathyroid hormone (PTH) were significantly elevated when compared to control values. In the vitamin D3-deficient diet group, there was a dose related increase in liver weight, liver-to-body weight ratio and kidney-to-body weight ratio. Serum cholesterol and 1,25-(OH)2D3 were significantly elevated. Urinary calcium decreased significantly with increasing HCB dosage, indicating conservation of calcium. The data from this study indicate that HCB does affect calcium metabolism by altering the concentrations of two primary controlling factors in calcium homeostasis. PMID- 3351980 TI - Calcium transport, thiol status, and hepatotoxicity following N nitrosodimethylamine exposure in mice. AB - The hepatotoxicant N-nitrosodimethylamine (NDMA) is presumed to exert toxicity through reactive metabolites. NDMA is similar in this respect to numerous other hepatotoxicants, for which hepatotoxicity is also associated with a rapid depletion of soluble and/or protein thiols, and an inhibition of calcium transport systems. We examined the hypothesis that hepatotoxicity for NDMA is preceded by thiol depletion and/or inhibition of calcium transport in isolated liver subcellular fractions. Centrizonal liver necrosis in mice was evident at 24 but not at 12 h subsequent to intraperitoneal administration of 40 mg NDMA/kg. Hepatotoxicity was not preceded by depletion of liver protein-free sulfhydryls, nor by protein sulfhydryl depletion in liver whole homogenate, microsomal, or plasma membrane fractions. NDMA-mediated toxicity was also not preceded by inhibition of calcium uptake capability by microsomal, mitochondrial, or plasma membrane fractions. In contrast, carbon tetrachloride produced the expected rapid decrease in microsomal calcium uptake capability, followed by a centrizonal necrosis that was maximal at about 24 h. These studies suggest that the mechanism of NDMA hepatotoxicity may differ from that of a number of other hepatotoxicants (e.g., carbon tetrachloride, acetaminophen, bromobenzene) for which toxicity is also mediated through reactive metabolites. PMID- 3351981 TI - Morphologic lesions and acute toxicity in rainbow trout (Salmo gairdneri) treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - To determine effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on growth, mortality, and morphologic lesions in rainbow trout, juvenile Shasta or Wytheville strain fish, obtained from 4 hatcheries, were administered graded single doses of TCDD, 0.1-125 micrograms/kg, ip. TCDD doses of 25 and 125 micrograms/kg caused 85% lethality 2-4 wk after treatment. At these high doses, death occurred before body weight loss could be detected. A lower dose of 5 micrograms/kg caused decreased growth and cumulative mortality of 20% after 11 wk. Stress associated with netting and weighing the fish at weekly intervals significantly shortened the delay period prior to TCDD-induced lethality. Gross and microscopic lesions were evident in rainbow trout treated with 10 micrograms TCDD/kg, but not in fish treated with 1 or 0.1 microgram/kg. Morphologic lesions occurred consistently in epithelial and lymphomyeloid tissues of TCDD-treated fish. Lymphomyeloid lesions included thymic involution, splenic lymphoid depletion, and hypocellularity of hematopoietic tissues in the head kidney and trunk kidney. In association with decreased hematopoiesis, peripheral leukopenia and thrombocytopenia occurred in Shasta strain yearling trout treated with 1 microgram/kg or more TCDD. Regarding epithelial lesions, all 4 hatchery strains treated with 10 micrograms/kg or more TCDD showed multifocal necrosis of gastric cardiac glandular mucosa, 3 of 4 hatchery strains showed vacuolar inclusions in exocrine pancreatic cells, and 2 of 4 hatchery strains showed fin necrosis. The severity and character of lesions in the liver and gastric mucosa varied markedly between hatchery strains of trout. One hatchery strain showed no hepatic lesions, two showed mild hepatocyte lesions, and one exhibited severe diffuse hepatopathy. In this severely affected hatchery strain, hyaline intracytoplasmic inclusions occurred in hepatocytes at 14 and 34 d after TCDD exposure, and bile-duct hyperplasia occurred at 34 d following TCDD exposure. One of 4 hatchery strains showed atrophy of serous gastric glands and 1 of 4 hatchery strains showed hyperplasia of these same glands at 25 and 34 d, respectively, following TCDD treatment. Thus, lymphomyeloid and epithelial tissues are the primary targets for TCDD-induced pathologic lesions in rainbow trout, and the incidence and severity of these lesions is influenced by the strain of trout used and the hatchery from which the trout were obtained. PMID- 3351983 TI - Disposition of 2-(2-quinolyl)-1,3-indandione (D. C. yellow #11) in rats dosed orally or intravenously. AB - The disposition of 2-(2-quinolyl)-1,3-indandione (D. C. yellow #11, DCY) in male Fischer rats dosed intravenously or by feeding was determined. For rats given [14C]DCY in the feed (0.00044-0.41% of the diet), recovery of radioactivity during the 24-h dosing period and the 72-h period thereafter ranged from 89.1 to 93.9% for feces and from 4.98 to 6.25 for urine. Tissues contained only trace amounts. Following intravenous dosing with [14C]DCY (0.93 mg/kg), radioactivity distributed readily into most tissues; maximum amounts were present at 5 min, the earliest time of assay. Maximum amounts of radioactivity in fat, skin, and gut tissue, however, were present at 30 min after dosing. These three tissues also had relatively long alpha phases for the elimination of radioactivity. In 24 h after intravenous dosing, rats excreted 81.1% of the dose in the feces and 16.0% of the dose in the urine. For rats fitted with biliary cannulas, 54.5% of the dose, all of which was metabolites of [14C]DCY, was recovered in the bile in 4 h. Associated with the rapid and extensive biliary excretion of metabolites of intravenously administered [14C]DCY was the appearance of large amounts of radioactivity in the feces and also, at intermediate time points, in the liver, gut contents, and gut tissue. In conclusion, rats rapidly distribute, metabolize, and excrete [14C]DCY. PMID- 3351982 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in yellow perch (Perca flavescens). AB - Growth, mortality and morphologic lesions in juvenile, hatchery-reared yellow perch, Perca flavescens, were studied after treatment with graded single doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1-125 micrograms/kg, intraperitoneally). TCDD doses of 25 and 125 micrograms/kg caused 95% mortality by 28 d after treatment, without decreasing body weight. A TCDD dose of 5 micrograms/kg resulted in progressive loss of body weight with cumulative mortality of 80% by 80 d posttreatment. Periodic handling stress did not affect the time course of mortality or cumulative percent lethality in TCDD-treated perch. Fin necrosis, petechial cutaneous hemorrhage, and ascites occurred in perch treated with 5 micrograms/kg or more of TCDD. Thymic atrophy, decreased hematopoiesis in the head kidney, fibrinous pericarditis, focal myocardial necrosis, submucosal gastric edema, and hyperplasia of the epithelium of gill filaments and lamellae occurred in perch dosed with 25 or 125 micrograms/kg. Dose related splenic lymphoid depletion occurred in perch receiving 5 micrograms/kg or more TCDD, and hepatocyte lipidosis occurred in groups treated with doses of 1 microgram/kg or more TCDD. Thus yellow perch are as responsive to the acute toxic effects of TCDD as some of the more sensitive mammalian species, and neither loss of body weight nor histologic lesions in TCDD-treated perch are sufficient to explain mortality. PMID- 3351984 TI - DNA strand breaks induced by hydrogen peroxide in isolated rat hepatocytes. AB - It has been proposed that increased rates of hepatic hydrogen peroxide (H2O2) production may initiate or promote the liver tumors that appear following chronic exposure of rodents to chemicals that cause peroxisome proliferation. However, the effect of H2O2 on the structural integrity of DNA in parenchymal hepatocytes, the target cells of peroxisome proliferator-induced carcinogenesis, is largely uncharacterized. Furthermore, oxidant-induced cellular damage has been invoked as causal of a number of hepatotoxic effects associated with exposure to chemicals other than peroxisome proliferators. For these reasons, alkaline elution analysis was used to study the action of H2O2, added exogenously, on DNA of intact, isolated rat hepatocytes. Addition of a bolus of H2O2 (0.01-1.0 mM) to monolayer cultures of hepatocytes caused concentration-dependent increases in single-strand DNA breaks (SSDB), which were maximal within 30 min of exposure. Cytotoxicity, as measured by lactate dehydrogenase (LDH) release, was minimal during a 1-h exposure to H2O2 concentrations less than 1 mM, but the efflux of oxidized glutathione was increased. Formation of SSDB was nearly linear with respect to H2O2 concentration in the range 0.1-1.0 mM. No double-strand DNA breaks or DNA protein crosslinks were identified at H2O2 concentrations of 1 mM or less. Repair of SSDB in H2O2-free medium occurred in a rapid, linear manner only for the first 15 min, resulting in disappearance of 65% of the SSDB. A second, slower phase of SSDB rejoining occurred between 20 and 60 min of incubation in H2O2-free media; at 60 min rejoining was maximal (80% repair). These results define a specific type of DNA damage associated with H2O2 exposure of hepatocytes and suggest that primary cultures of rat hepatocytes are a suitable model for characterizing the potential genotoxic effects of oxidants, particularly excess H2O2 that may occur in the livers of animals exposed chronically to peroxisome proliferators. PMID- 3351985 TI - The use of absorbable mesh in splenic trauma. AB - Previous reports from this hospital documented a splenic preservation rate of 50% (18/36) in adults after blunt and penetrating trauma. Recently (January through December 1984), use of an absorbable mesh helped to attain a 67% (22/33) salvage rate. The mesh is applied in such a fashion that it acts by tamponade. It proved useful in patients with bleeding from a large surface area or from deep parenchymal injuries, even those extending into the hilum. No deaths occurred in the splenic salvage patients. There was no difference in postoperative complications among the splenectomy, conventional splenorraphy, or mesh wrap splenorraphy groups. However, workup of persistent postoperative fevers in two splenic wrap patients revealed perisplenic fluid collections on CT scan. Aspiration yielded sterile fluid. Possible cause and effect relationship is being studied in the dog lab. We conclude that splenic wrapping is both a safe and efficacious method of splenic preservation. PMID- 3351987 TI - Functional recovery and medical costs of trauma: an analysis by type and severity of injury. AB - This study was designed to delineate the factors that influence the extent and rate of recovery as related to the characteristics and duration of functional limitations resulting from trauma. The study population was 597 surviving trauma patients aged 16-45 years from two trauma centers in a single state system which follow similar care protocols, and included patients with extremity, abdomen, thorax, brain, and spinal cord injuries. Of 479 trauma patients (80% of the total) who were followed for a full year, 57% had no activity restrictions, 16% had some limitation with either a major or minor physical activity, but did not have any difficulty with mobility or self care, and 27% were limited in either mobility or one of the five basic self-care activities. Further analyses show that of the 262 individuals who were working full-time before the injury, 57% had actually returned to full-time employment within the year. Factors in addition to type and severity of trauma that influence return to work were higher educational level, white collar employment, higher preinjury income, and the presence of supportive individuals among family or friends. Recovery as defined by functional status and return to full-time work is analyzed by body region and severity of the principal injury sustained. PMID- 3351986 TI - Urgent thoracotomy for pulmonary or tracheobronchial injury. AB - Three hundred eighty-eight of 7,283 (5.3%) admitted trauma patients underwent urgent thoracotomy. In 61 patients (15.7%), pulmonary or tracheobronchial injury prompted thoracotomy (11, blunt; 50, penetrating). Pulmonary hemorrhage necessitated thoracotomy in 54 patients (88.5%); tracheobronchial injury in five patients (8.2%). The mortality was 27.9%. Nine patients (14.8%) underwent pneumonectomy: eight died of intractable hemorrhagic shock during thoracotomy despite rapid control of pulmonary hemorrhage: one died of sepsis. Eleven patients (18.0%) underwent lobectomy: six (54.5%) died of concomitant injuries. Thirty-six patients (59.0%) underwent pneumonorrhaphy: one died of concomitant injuries. Five (8.2%) patients underwent tracheobronchial repair: one died of concomitant injuries. Pneumonectomy was uniformly fatal and should be a procedure of last resort in the treatment of pulmonary injury, as lobectomy and pneumonorraphy are better tolerated by these critically ill patients. PMID- 3351988 TI - Variables affecting outcome in blunt chest trauma: flail chest vs. pulmonary contusion. AB - We reviewed 144 consecutive patients with flail chest and/or pulmonary contusion between 1979 and 1984. The purpose was to analyze the factors adversely affecting morbidity and mortality. There were 97 males and 47 females, with an average age of 40 years +/- 18 S.D. (range, 2-83). Seventy-five per cent of the injuries were caused by motor vehicle accidents, with the remainder due to falls (17%), cardiopulmonary resuscitation (4%), altercations (2%), or falling objects (2%). The Injury Severity Score (ISS) averaged 32 +/- 14 S.D. in all survivors versus 60 +/- 14 S.D. in those who died. Eighty-three patients (58%) required mechanical ventilation. Thirty-six patients died (25%). Isolated pulmonary contusion or flail chest had a mortality of 16% each. However, the mortality more than doubled when there was a combined pulmonary contusion and flail chest (42%). More than half of all deaths were directly attributed to central nervous system injuries with another third due to massive hemorrhage. Factors that were associated with a higher morbidity and mortality included severe associated thoracic injuries, a high ISS, the presence of shock, falls from heights, and the combination of pulmonary contusion and flail chest. PMID- 3351989 TI - The utility of physiological status, injury site, and injury mechanism in identifying patients with major trauma. AB - It has been suggested that if triage criteria are to identify accurately patients with major trauma, not only physiologic status, but also anatomic site and injury mechanism must be assessed. This study examined the influence of physiologic, injury site, and injury mechanism criteria on the diagnosis of major trauma in 2,057 trauma patients. Because the Trauma Score was found to be a highly specific indicator of major trauma (98.7%), the strategy adopted for isolating the factors that minimize inappropriate triage was to determine which, alone or in combination, are the most effective in identifying patients with major trauma among those with high Trauma Scores (greater than 12). Based on this analysis, a set of triage guidelines was developed. The application of these guidelines to the study population indicated an undertriage rate of 4.1 to 6.3% and an overtriage rate of 16.8 to 21.3%, depending on the definition of major trauma. PMID- 3351990 TI - Management of vascular injuries in the lower extremities. AB - From 1981 through 1985, 220 consecutive patients with presumed vascular injuries in the lower extremities underwent operation at the Ben Taub General Hospital. More than 81% of injuries were due to penetrating wounds, and blunt and iatrogenic injuries accounted for the remainder. A preoperative emergency center arteriogram was performed in 63.2% of patients, and physical examination alone prompted operation in 36.8%. Eight patients underwent immediate amputation; the remaining 212 patients were found to have 225 arterial (63.9%) and 127 venous (36.1%) injuries. More than 50% of patients were noted to have both arterial and venous injuries. Arterial repair was most commonly accomplished by segmental resection with an end-to-end anastomosis (28.4%) or insertion of a graft (38.8%). Venous repair was most commonly accomplished by lateral venorrhaphy (48.8%), ligation (19.7%), or insertion of a conduit (18.1%). Postoperative infection in closed wounds, in wounds left open because of the magnitude of injury, and in adjacent fractured bone occurred in 13% of patients. Late amputations were necessary in only four patients, three of whom had infection as the cause. PMID- 3351991 TI - Lower extremity vascular trauma: a comprehensive, aggressive approach. AB - During this study, 25 patients (26 limbs) incurred 37 vascular injuries to the lower extremity. The majority were young males injured by penetrating trauma (84%). There were 25 arterial and 12 venous injuries (two isolated). Sixteen patients had soft-tissue injuries, 12 had fractures, and six had peroneal nerve damage. Twenty-two arterial injuries were repaired, the majority (17) by saphenous vein bypass. Three tibial vessels were ligated. All major venous injuries were repaired. No synthetic material was used. Vascular repair took precedence in all but two cases. After repair, the vascular surgeon assisted with stabilization. Thirteen limbs required fasciotomy; nine required subsequent debridements and later plastic reconstruction. Limb salvage was 96%. More important, 21 patients can ambulate independently on the injured extremity (84%). These results support an aggressive approach to lower extremity vascular trauma with repair of all major arterial and venous injuries in conjunction with aggressive debridement and soft-tissue repair. PMID- 3351992 TI - Septic complications associated with the use of peritoneal drains in liver trauma. AB - This study reviewed all 164 cases of liver trauma seen at the Charity Hospital of New Orleans from 1980 through 1984, in 12 of whom intra-abdominal abscesses formed. Thirty four per cent of the patients had no peritoneal drainage and an abscess rate of 1.8%, 18% had only closed suction drainage and 0% abscess rate, 15% had only open sump drainage and a rate of 8.3%, 14% had only open Penrose drainage with a rate of 8.7%, and 19% had a combination of both open Penrose and sump drainage with a rate of 22.5%. Certain findings or conditions were related to the development of postoperative sepsis. Gunshot wounds were associated with a 9.9% abscess rate, blunt trauma with 3.8%, and stabbings with 0%. Patients who presented in shock were at a threefold increased risk for intra-abdominal abscess formation, those who needed blood transfusions of greater than 6 units were at a tenfold increased risk, those with major liver injuries were at a sixfold increased risk, and those with a total of three or more abdominal organs injured were at a threefold increased risk for abscess formation. There was no significant relation between presence of gastrointestinal perforation and subsequent abscess formation. For patients without the specific risk factors mentioned above, the probability of developing an intra-abdominal abscess is low. This group of patients would therefore benefit little from the presence of a drain, but might very well be harmed by the introduction of external contaminant bacteria into the peritoneal cavity by the drain itself.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351994 TI - Risk of fatality from physical trauma versus sex and age. AB - No large-scale epidemiologic study to investigate how sex and age affect fatal trauma risk from the same impact has been possible previously because large numbers of people are rarely subject to sufficiently similar major physical insults. This paper describes such a study, made possible by two recent developments: first, the availability of a large data file, the Fatal Accident Reporting System, which gives information on more than one third of a million people fatally injured in traffic crashes; second, a new technique, the double pair comparison method, which, by focusing on vehicles containing two occupants, at least one of whom is killed, allows appropriate inferences to be made from such data. Fatality risk versus sex and age was determined for ten categories of vehicle occupants (unbelted car drivers, helmeted motorcycle passengers, etc.). Similar effects were found for different occupants, indicating that basic physiologic response (not confined to traffic fatalities) is being measured. It is found that fatality risk is about 25% greater for females than for similar aged males from about age 15 to 45 years. At younger and older ages males are more at risk. For both sexes, fatality risk is least at age 20 years. At age 70 it is about three times what it is at age 20. PMID- 3351993 TI - Granulocyte contamination of Ficoll-Hypaque preparations of mononuclear cells following thermal injury may lead to substantial overestimation of lymphocyte recovery. AB - During ongoing flow cytometric studies of burned patient blood leukocytes, it was noted frequently that large numbers of granulocytes were present along with the mononuclear cells at the plasma/Ficoll-Hypaque (F-H) interface following centrifugation over F-H. Since differential WBC counts are not routinely performed on F-H interface cells, it is possible that many previous immunologic studies of burned patients have greatly overestimated numbers of lymphocytes recovered. The present study sought to quantify the extent to which granulocyte contamination of F-H separated cells occurs following burn injury. Blood from 15 thermally injured patients (7-55% total body surface area burn) was studied serially at 24 hr, 48 hr, and weekly thereafter through 6 weeks postburn (PB). Controls were age-matched normals (No. of control bloods = 59). Three-part differential cell counts (lymphocytes, monocytes, and granulocytes) were performed on both F-H interface cells and RBC-lysed whole blood. Counts were performed by light scatter analysis on a flow cytometer. Except at 48 hr, at every time studied through 4 weeks PB, there was significant contamination of F-H interface cells with granulocytes. At 24 hr PB, 41 +/- 9% of the interface cells were granulocytes while at 4 weeks, PB 24 +/- 8% of the interface cells were granulocytes. The data did not support the interpretation that this increase in F H interface granulocytes was simply reflective of the granulocytosis commonly observed after burn. Thus artificial generation of granulocytosis by addition of extra normal leukocytes to normal blood resulted in complete separation of granulocytes from mononuclear cells following centrifugation over F-H.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3351995 TI - Fat embolism in patients with an isolated fracture of the femoral shaft. AB - Analysis of basic pathophysiologic variables in fat embolism patients is often restricted by the complexity of the different injuries present in each individual patient. To avoid this problem we investigated the presence of the fat embolism syndrome in patients with an 'isolated' fracture of the femoral shaft. Two groups were distinguished: those who had an open fracture or a closed fracture treated operatively within 24 hours after the accident (decompression group), and those who were treated initially conservatively (nondecompressed group). Clinical fat embolism occurred only in patients in the nondecompressed group (3.5%). They showed significantly higher initial temperatures, lower pulse rates, a progressive hemoglobin decrease, and a fracture localization more proximal (p less than 0.025) than the other patients in the nondecompressed group; they also showed significantly different pathophysiologic patterns from the patients in the decompressed group. Although the pathophysiologic mechanism of the onset of clinical fat embolism remains unclear, initial temperature elevations in combination with 'typical' fracture localization and fracture type appear to have a predictive value. PMID- 3351996 TI - Trauma associated with three and four-wheeled all-terrain vehicles. AB - Death or serious injury may occur as the result of accidents involving three- and four-wheeled recreational vehicles. Thirty-two cases of such trauma requiring hospitalization at the University of Missouri Hospital were reviewed, and followup questionnaires sent to each patient. Head and extremity trauma was nine times as frequent as torso injuries. Males were injured in 81% of the cases, and the average age of all patients was 18.6 years. Fifty per cent required intensive care monitoring and 74% required surgery. Two patients died of head injuries. Of the 25 survivors who responded to the questionnaires, 44% reported either inability to return to work or substantial interference with daily living due to their injuries. Inexperience riding the vehicle, prior use of alcohol, and lack of protective riding apparel were frequently cited as contributing factors in these injuries. PMID- 3351997 TI - All-terrain vehicle accidents in Maine. AB - All-terrain vehicles (ATV) are designed for off-road vocational or recreational use. Their popularity has increased steadily, but only recently has information accumulated concerning morbidity and mortality associated with the use of these vehicles. The 221 ATV accidents reported in Maine during 1985 are reviewed to more fully characterize the trauma associated with ATV accidents. These data are compared with reports from other geographical areas and recommendations made regarding ATV use. PMID- 3351998 TI - A comparison of nail-plate fixation and Ender's nailing in pertrochanteric fractures. AB - A randomized comparison was made of condylocephalic (Ender) nails and a nail plate technique (McLaughlin) for fixation of trochanteric fractures, to evaluate the consumption of acute hospital bed-days, number of reoperations, peroperative blood loss, and operation time. Reoperations were performed in 30% of the Ender group and in 10% of the McLaughlin group and blood loss was doubled for the McLaughlin method. Our study has shown, that in our hands, patients operated on with Ender nails had more reoperations, but in spite of this the total cost, in the form of days in hospital or operation time was not increased. PMID- 3351999 TI - Factors influencing the outcome of cervical spine injuries. AB - Factors such as cause of the trauma, concomitant injuries, and cervical sagittal spinal canal size were compared between survivors and nonsurvivors of cervical spine injuries. Traffic accidents were more commonly the cause of the trauma among nonsurvivors (76%) than among survivors (50%). Concomitant injuries were of a more serious degree among nonsurvivors than in survivors. Cervical sagittal spinal canal size was measured at the atlas level. Patients without any neurologic deficits had significantly (p less than 0.001) wider canals (24.1 mm) than fatalities (20.7 mm). The energy level at the moment of trauma and the cervical sagittal spinal canal size are of great importance for the survival prognosis and also probably for the genesis of various degrees of neurologic deficits. PMID- 3352000 TI - Traumatic anterior dislocation of the hip. AB - A case of traumatic anterior dislocation of the hip is presented. Reduction was easily achieved but was unstable because of disruption of the iliofemoral ligament by detachment of the anterior inferior iliac spine. A stable reduction was achieved by operative reattachment of the anterior inferior iliac spine. PMID- 3352002 TI - Retained knife blade and acute superior vena cava obstruction. AB - A case is described in which transfixation of the superior vena cava by the retained blade of a knife was the cause of acute caval obstruction. Use of a venous cannula as a stent allowed repair of the caval lacerations. PMID- 3352001 TI - Fracture of the femoral neck after internal fixation. AB - A case of femoral neck fracture despite the presence of a previously inserted sliding screw and sideplate is reported. Internal fixation in itself did not prevent subsequent fracture. A critical factor in the mechanism of this fracture was the patient's underlying disease, felt to be alcoholic osteomalacia. PMID- 3352003 TI - The Pediatric Trauma Score as a predictor of injury severity: an objective assessment. AB - The ability of the Pediatric Trauma Score (P.T.S.) to predict injury severity and mortality was evaluated by analysis of its relationship with the Injury Severity Score (I.S.S.) of 615 children entered into the National Pediatric Trauma Registry (N.P.T.R.). Mean age was 8.2 years and mortality was 3.5%. Mean I.S.S. of survivors was 8.1 in comparison to 59.7 for nonsurvivors. Linear regression coefficient determined from analysis of these variables produced a slope of -3.7 with a statistically significant correlation of P.T.S. to I.S.S. (p less than 0.001; r2 = 0.89). Analysis of the mortality for each cohort of patients with the same P.T.S. identified three categories of mortality potential. Children whose P.T.S. was greater than 8 had a 0% mortality. Children whose P.T.S. was between 0 and 8 had an increasing mortality related to their decreasing P.T.S. (r2 = 0.86), and children whose P.T.S. was below 0 had 100% mortality. This study documents the direct linear relationship between P.T.S. and injury severity, and confirms the P.T.S. as an effective predictor of both severity of injury and potential for mortality. PMID- 3352004 TI - Comparative outcomes of children and adults suffering blunt trauma. AB - In order to test the hypothesis that outcome from blunt traumatic injury is different for children and adults, a statistical method based on the TRISS Index was used to compare patient outcomes after blunt injury among three pediatric populations (N = 594 children: ages 0-3, ages 0-8, and ages 0-14) and an adult population (N = 7,809: ages 15-54 inclusive). There was no statistical difference in predicted outcome between these populations. Using a methodology that accounts for both anatomic injury description and physiologic response (TRISS), the survival probability function does not appear to be age dependent below 54 years. PMID- 3352005 TI - Video recording trauma resuscitations: an effective teaching technique. AB - Since the initial hour after injury is the most crucial time for trauma patients, resuscitation technique is of vital importance. Standardized courses for first hour management (ATLAS) have been widely accepted. A teaching format based upon video recording of every resuscitation has been developed. Tapes are reviewed by the staff and by the individuals involved in a particular resuscitation. In a weekly resuscitation review conference, actual footage is presented to the trauma team members, specific aspects of a resuscitation are critiqued, and supplemental didactic information is presented. Legal problems have been avoided by making the review and conference a part of the quality assurance process. Patient anonymity is preserved by positioning the video camera at the foot of the resuscitation bed. Tapes are erased after each conference. Video recording allows analysis of: 1) priorities during the resuscitation; 2) cognitive integration of the workup by the team leader; 3) physical integration of the workup by the team leader; 4) team member adherence to assigned responsibilities, resuscitation time, errors or breaks in technique; and 5) behavior change over time. In 3 1/2 years, more than 2,500 resuscitations have been recorded. Over a 3-month period, average resuscitation time to definitive care decreased for age- and injury severity matched patient groups cared for by one team. Resuscitations have become more efficient and adherence to assigned responsibilities better. Weekly review of resuscitation contributes to improved technique and trauma care. PMID- 3352007 TI - Effects of total hip replacement and bed rest on blood rheology and red cell metabolism. AB - In order to better understand the pathophysiologic changes in the immediate postoperative period after total hip replacement surgery and to distinguish alterations due to the surgical operation from those due to bed rest, we examined rheologic parameters and red cell metabolism of patients before, 1 day after, and 5 to 6 days after total hip replacement and compared the results to those obtained from normal volunteers placed at bed rest for 5 days. Bed rest in the control group led to increases in hematocrit, mean corpuscular hemoglobin concentration, red cell DPG and ATP levels, and plasma concentrations of total proteins, globulins, and fibrinogen, with attendant increases in whole blood viscosity, plasma viscosity, blood viscosity, relative blood viscosity with hematocrit adjusted to 45%, and viscometric aggregation index, and the viscosity of red cell suspensions in Ringer's solution at 45% hematocrit decreased at low shear rate. The patient group, despite the postoperative lowering of their hematocrit, mean corpuscular hemoglobin concentration, and total plasma proteins and a consequent decrease of whole blood viscosity, revealed disproportionate increases in blood viscosity, relative blood viscosity, and viscometric aggregation index. These rheologic changes, which reflect an enhanced red cell aggregability, may contribute to complications of thrombophlebitis. Enforced inactivity, when superimposed on the effects of trauma, blood loss, transfusion with bank blood, and the low-flow state, would exaggerate these rheologic problems. The results suggest that management of total hip replacement patients should include hemorrheologic considerations (e.g., preoperative intentional hemodilution) and early postoperative activity. PMID- 3352006 TI - Resuscitative thoracotomy: the effect of field time on outcome. AB - In the past 5 years, 72 moribund patients have undergone resuscitative thoracotomy (RT) at the Medical University of South Carolina: 62 patients underwent the procedure before the adoption of a policy of mandatory rapid transport (scoop and run) for penetrating and unstable victims of trauma by our EMS system (Group I). Group II is comprised of ten patients who underwent RT following adoption of this policy. Resuscitation was successful in three patients in Group I (4.8%) and there were only two survivors (3.2%). In contrast, resuscitation was successful in two of ten patients in Group II (20%) and there was one survivor (10%). Nineteen patients in Group I (31%) were in traumatic full arrest on the scene, all of whom died. Twenty-five patients in Group I (40%) had a measureable pulse and/or blood pressure when EMS personnel arrived at the scene and subsequently "died" before their arrival at the trauma center. RT was also uniformly unsuccessful in this subgroup. Eighteen patients in Group I (29%) suffered cardiac arrest following their arrival at the hospital. Three of these patients (16.6%) were successfully resuscitated and two (11%) survived to leave the hospital. There were four traumatic full arrests in Group II (40%) and all four died. Only two patients in Group II (20%) lost their vital signs in transport and both died. Four patients in Group II (40%) suffered cardiac arrest after arrival at the hospital. Two of these patients (50%) were successfully resuscitated and one left the hospital (25%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352008 TI - Useful ICP monitoring with subarachnoid catheter method in severe head injuries. AB - ICP in 233 patients with severe head injuries was monitored utilizing a subarachnoid catheter technique. The relationships between initial ICP and GCS, between initial ICP and GOS, between maximal ICP and GCS, and between maximal ICP and GOS were examined statistically. The correlation was significant in each case, but particularly so between maximal ICP and GOS. Thus morbidity and mortality may be dependent upon maximal ICP. Catheterization of the subarachnoid space presents little difficulty using a Tuohy needle for epidural anesthesia as an introducer. Though the catheter is very fine (1.0 mm in outer diameter), failure of waveform occurred in only 2.1% of all patients. The procedure can be easily performed at the bedside, is safe, inexpensive, and useful for the management of severe head injuries. Meningitis was recognized in 4.7% of all patients. PMID- 3352010 TI - Patterns of high-speed impact injuries in motor vehicle occupants. AB - Trauma from high-speed motor vehicle accidents is a leading cause of death and disability. Most of these injuries could be prevented if the driver and occupants of motor vehicles wore seatbelts or used other restraining devices. The injuries produced when an unrestrained occupant of a motor vehicle is ejected from that vehicle or impacts on a hostile surface at high speed occur in a reproducible pattern. The types of injuries sustained by drivers and front seat passengers are different and specific enough to allow one to identify drivers and passengers with confidence. Because of severe life-threatening injuries to the central nervous system, and thoracic and abdominal viscera, other serious injuries may be overlooked. Knowledge of the mechanism of injury and the role of the victim (i.e., driver or passenger) should lead to the prompt radiographic evaluation of all areas at risk. Our findings are based on a study of 250 drivers and 250 front seat passengers involved in motor vehicle accidents. We found distinct common injury patterns and radiographic findings in drivers and front seat passengers. PMID- 3352009 TI - Acute cardiovascular effects of experimental spinal cord injury. AB - The effects of acute head injury or subarachnoid hemorrhage on the cardiovascular system (CVS) are well known, but data are lacking on the effects of acute spinal cord injury (SCI) on the CVS. The clip compression SCI rat model was used to measure changes in the mean systemic arterial pressure (mSAP), cardiac output (CO), heart rate (HR), total peripheral resistance (TPR), and central venous pressure (CVP) after SCI. Three groups of five animals each were anesthetized with chloralose-urethane: one group underwent only the surgical procedures including laminectomy, and the other two received either a 2.3- or 53.0-gm injury at the T1 spinal cord segment for 1 minute. The CO was measured using the thermodilution technique. CVS parameters were measured before injury, and then at designated times for 135 minutes after SCI. Analysis of variance and paired t test with significance at p = 0.05 were used for analysis. There were no CVS changes as a result of anesthesia, operative time, or laminectomy alone. Cardiovascular system (CVS) changes occurred after the 2.3- and 53.0-gm. injuries but were significantly different only in the 53.0-gm injured animals. In this group mSAP increased from a preinjury value of 105 +/- 8 mm Hg to 178 +/- 11 mm Hg as a result of SCI, followed by a prolonged period of hypotension (46 +/- 15 mm Hg) lasting until 135 min post SCI. The CO after SCI also decreased from 394 +/- 22 to 218 +/- 29 ml/min/kg with the TPR reaching a minimal level at 45 min post SCI (265 +/- 23 to 213 +/- 29 mm Hg/ml/min gm wt), after which it returned to preinjury values. There were no significant changes in the CVP in either group. In the 53.0-gm group significant bradycardia (492 +/- 7 to 356 +/- 44 beats/min) was observed by 45 min and continued to decrease until 135 min after SCI. Thus the CVS showed two major alterations after severe SCI: post-traumatic hypotension, and a parallel decline in CO. There were no major changes in TPR, HR, or CVP, although HR ultimately declined. These findings suggest that the decline in CO was not entirely due to decreased sympathetic tone, but may also have resulted from direct myocardial injury, similar to that demonstrated after head injury or subarachnoid hemorrhage. PMID- 3352012 TI - Avulsion fracture of the tibial tuberosity in late adolescence. AB - Between January 1982 and May 1985, eight patients with avulsion fractures of tibial tuberosity were seen at the University of South Alabama Medical Center. All were boys, average age, 15 years 8 months. Six of eight had a positive history of Osgood-Schlatter disease. Seven patients underwent open reduction and internal fixation, one had closed reduction and cast. Followup ranged from 5 months to 3.5 years, averaging 19.5 months. All, except one who had lateral meniscectomy, regained practically full ROM and reported no pain or limitation of activities. No patient developed genu recurvatum deformity or leg length discrepancy due to the injury. Open reduction and internal fixation is the treatment of choice in displaced intra-articular fractures. Lateral parapatellar incision is a more direct approach to this fracture and is less likely to injure the infrapatellar branch of the saphenous nerve. PMID- 3352011 TI - The role of IVP in blunt trauma. AB - To investigate the role of the IVP, we studied 139 patients with blunt abdominal trauma and hematuria. Multivariate analysis of clinical parameters was utilized in attempt to predict which patients would have abnormal IVP's and which would eventually require genitourinary operation. Thirty-four patients (25%) demonstrated abnormalities on IVP; however, no combination of clinical findings (including degree of hematuria) could reliably predict which patients would have abnormal IVP's. On the other hand, in 90% of the patients, the necessity for genitourinary operation could be reliably predicted based on: presence of blood at the urethral meatus, degree of hematuria, patient age, Injury Severity Score, and number of rib fractures. We conclude that to detect IVP abnormalities, IVP's need to be performed on all blunt trauma patients with hematuria. However, patients likely to have injuries requiring operative repair can be predicted. Those patients unlikely to have genitourinary injury requiring repair, therefore, may have IVP performed on a nonurgent basis. PMID- 3352013 TI - Operative treatment of displaced intra-articular fractures of the calcaneus. AB - Thirty-five patients with 41 calcaneus fractures, seen at Cook County Hospital over a 3 1/2-year period, underwent an open reduction and internal fixation of their fractures through a sinus tarsi incision. Bohler's angle averaged 6 degrees preoperatively and 26 degrees postoperatively. An additional measurement, the critical angle, was defined. This angle is a measurement of the congruency of the posterior facet. It facilitated the selection of patients for an open reduction as well as allowed a determination of the adequacy of restoration of the joint surfaces postoperatively. In this series the critical angle averaged 26 degrees preoperatively and 1 degree postoperatively. Followup was possible in 73% of the patients. Almost all of the patients exhibited some degree of limitation of motion of the subtalar joint, but the reduction of the fracture fragments was maintained in all cases and secondary deformity and complaints did not develop. PMID- 3352014 TI - Hyperglycemia is not a poor prognostic sign in head-injured children. AB - Hyperglycemia among adult trauma patients with head injuries is a recognized phenomenon which has been shown to be associated with a poor prognosis when it takes the form of nonketotic hyperosmolar hyperglycemia. It is not known to what extent a similar phenomenon occurs in pediatric patients, although it is known that a child's physiologic response to injury, particularly to neurologic injury, is often different than an adult's. This study was undertaken to characterize the hyperglycemic response of children with closed head injury compared to children with a non-head injury, and to measure the extent to which the presence of hyperglycemia is associated with a poor outcome among children with severe head injury. Records for all children ages 2 to 12 years admitted to a major regional trauma center with closed head injury over a 6-year period were compared to the records of a control group of children hospitalized for a non-head injury. The hyperglycemic response was more common among those with head trauma, occurring in 40% compared to 5% of the controls (p less than 0.001); however, the level of hyperglycemia could not be associated with any indicator of outcome. The entity known as nonketotic hyperosmolar hyperglycemia did not occur in any of these patients. Apparently, the hyperglycemia associated with closed head injury in children is transient, does not need to be treated with insulin therapy, and in contrast to what has been demonstrated in adult trauma patients, does not predict patient outcome. PMID- 3352015 TI - Atypical downhill skiing injuries. AB - To evaluate the incidence and types of atypical ski injuries, charts and X-rays of all patients brought to Pocono Hospital with ski injuries between October 1984 and March of 1985 were reviewed. Atypical injuries occurred in only 5% of those seeking medical attention, but accounted for 67% of those requiring immediate hospitalization. Prompt recognition is essential for proper treatment of these potentially life-threatening injuries. PMID- 3352016 TI - Survey of factors influencing injury among riders involved in motorized two wheeler accidents in India: a prospective study of 302 cases. AB - Two-wheeler trauma in developing countries differs in some respects when compared to that in developed countries. A total of 302 cases involved in motorcycle, scooter, and moped accidents were analyzed. There were 201 drivers and 101 passengers. Injury severity scores (ISS), overall number of wounds, and number of fractures were studied. Motorcycle riders had a significantly higher ISS than did scooter riders. Persons involved in collisions with other powered vehicles had 36% more fractures and higher ISS than those involved in accidents where no collision occurred with a powered vehicle. Female passengers, sitting sideways, and involved in collisions, sustained fewer injuries than did a comparable group of male passengers who sat astride; the ISS of female passengers was also lower. Helmet users had a much lower incidence and severity of head injury than riders who did not use helmets. Turbans appeared to offer partial protection from head injury. PMID- 3352017 TI - Ligation as definitive management of injury to the superior mesenteric vein. AB - Ligation of the injured superior mesenteric vein in patients with multisystem trauma has been regarded as a hazardous procedure with a narrow spectrum of indications. We present three patients who underwent ligation of their superior mesenteric veins. A collective review of 33 superior mesenteric vein ligations and 75 superior mesenteric venorrhaphies indicated that ligation of this vein is indeed a valid option when a simple repair cannot easily be performed. PMID- 3352018 TI - Proximal upper limb replantation in children. AB - Proximal upper limb amputation not only leads to serious local disability but carries with it substantial systemic implications. The replantation of an avulsed limb is all too frequently followed by disappointing functional results. In children, however, with secure bony stability, vascular reconstruction and immediate appropriate nerve repair the results of replantation can be most gratifying. Two such cases have been seen at The Hospital for Sick Children and are reported in detail. The late functional results as illustrated make this complex procedure a very worthwhile undertaking. PMID- 3352019 TI - Preoperative percutaneous intraluminal balloon catheter control of major arterial hemorrhage. AB - Preoperative percutaneous balloon catheter control of major arterial hemorrhage is a useful technique when the damaged vessel is difficult or dangerous to expose. We report two cases, one with a gunshot wound to the internal carotid artery and one with a ruptured splenic artery aneurysm, in whom this approach was successfully employed to stop hemorrhage, control shock, and allow a precise, controlled vascular exposure and repair. PMID- 3352020 TI - Ileal entrapment as a complication of fractured pelvis. AB - A case of entrapment of small bowel in a fracture of the pelvis is presented. It was found on laparotomy in the present case, but contrast enema or computerized tomography have been reported as diagnostic of this rare, life-threatening condition. PMID- 3352021 TI - Retropharyngeal hematomas. AB - Hyperextension of the cervical spine in the elderly can cause retropharyngeal hematomas. We report this unusual cause of retropharyngeal hematoma in a 77-year old women. The airway must be thoroughly evaluated in any such patient in whom this lesion is suspected. PMID- 3352022 TI - Free intraperitoneal rupture of a pancreatic pseudocyst: a presentation of acute abdominal trauma. AB - A rare case of traumatic rupture of a pancreatic pseudocyst is presented. Its unique aspect is definitive pseudocyst drainage via a Roux-en-Y cystjejunostomy at initial laparotomy. PMID- 3352023 TI - Visual loss following traumatic asphyxia in children. AB - Two young children suffered loss of vision in separate incidents following traumatic asphyxia. Visual loss secondary to trauma can occur from a variety of causes. This is apparently the first description of traumatic asphyxia causing visual loss in children. In children, visual impairment is easily missed unless the degree of handicap is severe. All children should have their fundi and visual acuity assessed before discharge following significant trauma, including all episodes of traumatic asphyxia. PMID- 3352024 TI - Extracorporeal shock wave lithotripsy using a new, compact and portable unit. AB - We report on the use of a new compact, inexpensive, portable shock wave lithotriptor. To date 40 treatments on 37 patients with different calculi in the upper urinary tract have been performed at our institution with excellent results and no complications. More patients currently are being treated with this machine at additional centers with equally good results. PMID- 3352025 TI - Extracorporeal shock wave lithotripsy-induced perirenal hematomas. AB - Subcapsular or perirenal bleeding is the most commonly experienced adverse effect directly attributable to externally applied shock waves. The first consecutive 3,620 extracorporeal shock wave lithotripsy treatments with the HM3 Dornier lithotriptor at our institution resulted in 24 hematomas in 21 patients, for an incidence of 0.66 per cent. Various factors associated with treatment were examined. The number of shock waves (up to 2,000) and voltage up to 24 kv. did not correlate with the development of hematoma. Coagulation studies were normal in all patients with hematomas. There was no correlation of patients size and weight, or stone size, number or location with the occurrence rate of perinephric hematoma. Patients with pre-existing hypertension, particularly those with unsatisfactory control of hypertension, had a significantly increased incidence of perinephric hematoma. The incidence of hematoma in hypertensive patients was 2.5 per cent and it increased to 3.8 per cent in patients with unsatisfactory control of hypertension. Therefore, pre-existing hypertension is a significant risk factor in the occurrence of post-extracorporeal shock wave lithotripsy bleeding. The incidence of perinephric hematoma also was increased in patients with pre-treatment urinary tract infection and those who underwent simultaneous bilateral treatment. Management of post-extracorporeal shock wave lithotripsy bleeding generally is conservative although a third of the patients required transfusion. PMID- 3352026 TI - The role of posterior lumbotomy in the management of surgical stone disease. AB - A total of 50 consecutive patients underwent posterior lumbotomy for removal of upper third ureteral or renal pelvic stones between June 1983 and October 1986. Morbidity was low, hospitalization was brief and 100 per cent of the patients were rendered free of stones postoperatively. Dorsal lumbotomy compares favorably with other currently available methods for the management of selected patients with calculous disease. PMID- 3352027 TI - Creatinine clearance prediction in spinal cord injury patients: comparison of 6 prediction equations. AB - The renal function of spinal cord injury patients frequently is overestimated by 3 commonly used equations to predict creatinine clearance. Overestimation of creatinine clearance may result in aminoglycoside overdosage and resultant nephrotoxicity. Three newer prediction equations have been developed from creatinine clearances measured in neurologically abnormal patients. These 6 equations were tested in 77 male and 9 female spinal cord injury patients (48 quadriplegics and 38 paraplegics, including 38 with acute and 48 with chronic injuries). The equation developed by Sawyer and Hutchins was superior to 2 other equations developed in spinal cord injury patients and 3 equations developed in neurologically normal patients. However, creatinine clearances predicted by this equation were within 30 ml. per minute of measured creatinine clearances in only two-thirds of the spinal cord injury patients. Errors ranged from overestimation by 95 ml. per minute (151 per cent) to underestimation by 106 ml. per minute (45 per cent). The potential for large errors in creatinine clearance prediction necessitates measurement of creatinine clearance as soon as possible when renal excreted and toxic pharmaceuticals are administered to spinal cord injury patients. PMID- 3352028 TI - Ureteroscopic results and complications: experience with 130 cases. AB - Since its introduction for general use, the role of rigid ureteroscopy in the diagnosis and therapy of urological disease has been in evolution. We evaluated retrospectively the experience at our institution with rigid ureteroscopy from January 1983 to July 1986 in an attempt to identify clinical situations or techniques that tended to increase the incidence of either success or complications. We determined that ureteroscopic complications were rare in procedures performed for diagnosis compared to those performed for calculi (2 of 33 or 6 per cent versus 27 of 99 or 27 per cent, p less than 0.025). The likelihood of failure or complication was greater for stones above than for those below the pelvic brim (15 of 25 or 60 per cent versus 26 of 75 or 35 per cent, p less than 0.05). Major complications were more common early in our experience (9 of 63 or 14 per cent versus 2 of 69 or 3 per cent for the combined years 1983 and 1984 compared to 1985 and 1986, p less than 0.05). Our success rates in the treatment of calculous disease were similar to those reported previously, and they were somewhat better for stones located below (62 of 75 or 83 per cent) than for those above (17 of 25 or 68 per cent) the pelvic brim. Based on our findings we conclude that carefully performed diagnostic ureteroscopy has little potential for major complications, ureteroscopy for stones above the pelvic brim should be avoided when possible, and an increased rate of complications and failures is expected early in any series owing at least partly to the learning curve effect. PMID- 3352029 TI - The continent ileal bladder for urinary tract reconstruction after cystectomy: a survey of 44 patients. AB - The continent ileal bladder is an ileal pouch that is anastomosed to the urethral stump for urinary diversion after radical cystectomy. The ureters are implanted by an antireflux nipple ureteroileostomy. We report our results in 44 patients who underwent this type of diversion. The perioperative morbidity and mortality were comparable to those of an ileal conduit diversion. Urodynamic evaluation showed the ileal bladder to be a low pressure reservoir with a capacity that increased to more than 300 ml. The ileal bladder was emptied by straining without significant residual urine in all patients. After a training period of a few months all patients were continent in the daytime. However, some patients required pads at night because of occasional loss of urine. PMID- 3352030 TI - Long-term followup of 103 patients with bladder exstrophy. AB - We reviewed 103 patients with exstrophy of the bladder. Followup was more than 15 years in 51 patients. Initial management consisted of primary bladder closure in 32 patients and urinary diversion in 71. Urinary continence, renal function, urinary tract infections and development of malignant lesions were evaluated. Factors leading to success or failure were analyzed. Although the highest continence rate (83 per cent) was achieved in 40 patients with ureterosigmoidostomy, renal functional deterioration was highest in this group, with 70 per cent of the evaluable renal units being abnormal. Furthermore, 10 per cent of this group died of renal failure and 23 per cent lost 1 kidney each. In 26 patients with an ileal conduit 69 per cent of the renal units evaluated were abnormal. Only 1 patient died of renal failure but 27 per cent lost 1 kidney each. Of 32 patients with primary bladder closure 31 had preservation of renal function. Twelve of 18 patients (67 per cent) in whom vesical neck reconstruction had been completed had total urinary continence and 3 (17 per cent) had partial continence. The incidence of significant urinary tract infections was highest in the ureterosigmoidostomy group (63 per cent) and next to the highest in the ileal conduit group (48 per cent). Malignant lesions developed in 8 patients (8 per cent). PMID- 3352031 TI - Stress incontinence: classification and surgical approach. AB - We present a modified classification for stress urinary incontinence based on the nature of vesical neck descent and the integrity of the intrinsic sphinteric mechanism. Surgical treatment was undertaken in 72 patients with this classification. With a minimum followup of 18 months there was a 94 per cent cure rate with respect to stress incontinence. However, in 14 patients significant frequency and urgency developed, which persisted for at least 6 months postoperatively. Of these patients 13 had undergone a pubovaginal sling procedure, 3 of whom had refractory symptoms, including urge incontinence, which resulted in augmentation cystoplasty in 2 and supravesical urinary diversion in 1. PMID- 3352033 TI - Functional evaluation of penile hemodynamics. AB - A multidisciplinary study was performed on 200 consecutive patients with erectile dysfunction more than 1 year in duration, which included a standardized intracavernous injection of a vasoactive substance mixture (15 mg. per ml. papaverine plus 0.5 mg. per ml. phentolamine). The multidisciplinary findings correlated well with the intracavernous dose needed for full erection. The group without pathological hemodynamic findings (36 patients) needed an average of 0.67 ml. and the group with pathological inflow (107) needed an average of 1.07 ml. In the venous insufficiency group (57 patients) only 18 achieved full erections with an average of 2.1 ml. (39 achieved tumescence only to 3 ml.). The results show that standardized intracavernous injection of a vasoactive substance mixture is a useful method to evaluate penile hemodynamics. This pharmacological test appears to be effective in the differential diagnosis of nonvascular and vascular erectile dysfunction. PMID- 3352034 TI - Dystrophic penile calcification in Peyronie's disease. AB - Plain film radiography was performed in 66 consecutive patients with Peyronie's disease. Dystrophic calcification was noted in 22 patients (33 per cent). Patients with dystrophic calcification were younger (p less than 0.025) and had a more severe deformity (p less than 0.05) than those without calcification. PMID- 3352032 TI - Opacification of the glans penis during cavernosography. AB - Cavernosography and cavernometry were performed in 150 impotent patients and 10 normal potent volunteers. Opacification of the glans penis was noted in 5 normal volunteers, while among the impotent patients it was noted in 53 per cent of those with venous leakage and in 36 per cent of those without leakage. We believe that opacification of the glans during cavernosography must be regarded as a normal variant rather than as a sign of pathological shunts between the glans and the corpora cavernosa. PMID- 3352035 TI - Implantation of model AMS 700 penile prosthesis: long-term results. AB - The American Medical Systems inflatable penile prosthesis has undergone periodic design changes to improve device reliability and longevity while maintaining a high degree of patient and partner satisfaction. Previous data reported from this institution did not consider these frequent design changes and the assessment of device reliability incorporated consecutive cases involving several different designs. This study was designed to evaluate followup data on 120 patients who received the model 700 inflatable penile prosthesis, permitting assessment of device reliability of a single design. Two groups were evaluated: a pre-fix group of 57 patients and a post-fix group of 63 patients. Over-all, 11.7 per cent of the total group required revision (21 per cent of the pre-fix and 3.2 per cent of the post-fix groups). Careful life-table analysis of the results with the current model 700 device (post-fix) reveals that this model has a 97 per cent chance of maintaining normal mechanical function for 3 years. Further assessment of these patients in the future will provide additional data on long-term reliability of this design. PMID- 3352037 TI - Value of early operation in blunt testicular contusion with hematocele. AB - The use of ultrasound for evaluation of blunt testicular injury with hematocele allows contusion to be differentiated from rupture, and some authors advocate reserving surgical management for rupture. Our experience with the conservative management of 20 men with testicular contusion and hematocele was not encouraging. Of the patients 8 (40 per cent) required delayed exploration that involved orchiectomy in 3 (15 per cent) because of unresorbed hematoma or infection despite antibiotic use. In contrast, early surgical exploration in 19 patients reduced the morbidity and duration of disability, and resulted in an orchiectomy rate of 0. PMID- 3352036 TI - Severe penile curvature after implantation of an inflatable penile prosthesis. AB - We describe 6 cases of penile curvature following implantation of inflatable penile prostheses. Exploration revealed severe scarring of the corpora cavernosa, which produced the curvature in 4 patients. In all 4 cases this area was incised and the defect was filled with a polytetrafluoroethylene vascular graft. The penis was straightened and the prosthesis functioned normally. The remaining 2 patients were treated with inflation for 8 weeks with resolution of the curvature. To our knowledge, these cases represent the first reported complications produced by abnormal scar tissue outside of the inflammatory pseudocapsule after implantation of an inflatable penile prosthesis. PMID- 3352038 TI - Familial double testicular tumors: identical chromosome changes in seminoma and embryonal carcinoma of the same testis. AB - An identical abnormal chromosome, i(12p), and a marker chromosome of unknown origin were seen in 2 tumors of different histology (seminoma and embryonal carcinoma) in the same testis. A younger brother of the patient also had undergone orchiectomy for 2 seminomas in the left testis 2 years previously. These findings are discussed in relation to the possible cellular background of testicular tumors and their genetic parameters. PMID- 3352039 TI - Papaverine testing of impotent patients following nerve-sparing radical prostatectomy. AB - To investigate the etiology of impotence following nerve-sparing radical retropubic prostatectomy we performed papaverine testing on 23 patients who did not regain erections sufficient for vaginal penetration. Intervals from surgery to testing ranged from 3 to 30 months, with an average of 9 months. All patients achieved some degree of tumescence. In response to intracavernous papaverine injection only 1 patient (5 per cent) obtained an erection equivalent to the preoperative state. Of 18 patients who were fully potent preoperatively 8 (44 per cent) achieved an erection less than normal but judged to be sufficient for intercourse by the examining physician. Twelve patients, including 2 who were not fully potent preoperatively, had erections of poor quality insufficient for vaginal penetration. The results suggest that in most of these patients postoperative erectile dysfunction is predominantly vasculogenic in origin. Thus, factors other than injury to the neurovascular bundles may be responsible for postoperative impotence. PMID- 3352041 TI - Value of acetic acid screening for flat genital condylomata in men. AB - Application of acetic acid solution to the genital skin followed by magnified examination permits the detection of grossly inapparent flat condylomata acuminata. To evaluate the accuracy of this screening method, the male sexual partners of 36 women with genital condylomata were examined by this method and biopsies were obtained when results were positive. Of 47 biopsies of acetowhite (the whitish change that occurs when an epithelial surface is stained with acetic acid) lesions there were 26 cases of histologically confirmed condylomata, 9 of koilocytotic atypia and 12 with false positive results. There were 25 men whose sexual partners had cervical condylomata and cervical dysplasia. In this subgroup, considered to be at higher risk for flat condylomata, the screening method revealed 15 cases of condylomata, 6 of koilocytotic atypia and 4 in which no changes by acetic acid could be found. The extensive involvement of genital skin with flat condylomata in this subgroup raises doubts as to the practicality of treatment. Nevertheless, before treatment is rendered a punch biopsy for confirmation of the screening test is advised. PMID- 3352040 TI - Pharmacological treatment of erectile dysfunction after radical prostatectomy. AB - The potential for potency after radical retropubic prostatectomy has improved considerably since the anatomical description of the neurovascular bundles to the penis and a technique whereby these nerves may be spared from injury. However, impotence remains an unavoidable complication in some patients. It is in such patients that we have chosen to evaluate the technique of intracavernosal injection of a papaverine/phentolamine mixture to obtain erections. After classical radical prostatectomy potency was restored by the injection technique in 12 of 14 patients (85 per cent). Three patients who failed to attain erections initially had successful results with larger doses. Two patients who failed to achieve erections had the lowest penile brachial index values and 1 in whom priapism developed had the highest value, indicating that this may be a useful technique to determine the initial dosage of the injection. PMID- 3352042 TI - Polyuric urinary tract dilatation with renal damage. AB - Polyuria of diabetes insipidus and psychogenic polydipsia can produce massive dilatation of the urinary tract in the absence of any mechanical obstruction. Renal failure in these cases is rare. We report the second case of nephrogenic diabetes insipidus with nonobstructive hydronephrotic renal damage. Temporary suprapubic drainage restored renal function to normal and decreased the upper tract dilatation. Renal function has been preserved for more than 10 years. Surgical intervention beyond temporary vesical drainage is unnecessary. PMID- 3352043 TI - Ileocecal bladder augmentation in myelodysplasia. AB - We discuss 14 children and adolescents with myelodysplasia who underwent bladder augmentation with the ileocecal segment. The bowel was not detubularized nor was the ileocecal valve intussuscepted. Urodynamic evaluation was performed before and after the procedure in 13 patients with a followup of 1 to 8 years. Postoperative capacity and compliance were normal but cecal contractions occurred in 8 patients despite adequate doses of anticholinergics. Reflux was demonstrated at capacity with a cecal contraction in 4 patients but upper tract dilatation and infection were not clinical problems. Three patients required reoperation for complications owing to ureteroileal stenosis and/or urinary tract calculi. Although the clinical results were satisfactory, detubularized segments of bowel with intussuscepted afferent loop valves to prevent reflux may resolve these problems in the future. PMID- 3352044 TI - Augmentation cystoplasty in the failed exstrophy reconstruction. AB - Of the 148 patients with bladder exstrophy seen at this institution during the last 10 years 12 have ultimately required bladder augmentation. In 4 cases augmentation was performed for an inadequate bladder capacity, upper tract decompensation and dry interval of less than 1 hour after bladder neck reconstruction and epispadias repair. Likewise, 3 patients underwent augmentation for an inadequate bladder capacity and dry interval of less than 2 hours after bladder neck reconstruction and epispadias repair. Of these 7 patients 3 had undergone 2 previous bladder neck reconstructions, while 4 had undergone 1 prior repair. Five augmentations were performed for an inadequate bladder capacity before any type of continence procedure had been done. Nine patients underwent adjunctive procedures in addition to bladder augmentation, including a Young-Dees Leadbetter procedure in 4, an artificial urinary sphincter in 3, transureteroureterostomy and psoas hitch in 1, and a Mitrofanoff procedure and bladder neck closure in 1. Of the 12 patients 11 are continent, although 9 require intermittent catheterization. There were no major complications. However, 1 artificial urinary sphincter was removed for erosion 2 years after placement. Augmentation cystoplasty has provided prolonged stability of the upper tracts and continence in these patients, and it has proved to be a successful alternative to urinary diversion in this select group of exstrophy failures. PMID- 3352046 TI - Congenital neuroblastoma presenting as a paratesticular tumor. AB - A 1-month-old male newborn was operated upon for a scrotal tumor that was localized outside of the testis. Histological diagnosis was neuroblastoma. Although neuroblastoma often may present as metastatic disease when first seen, this case is unique in that an undetected adrenal neuroblastoma presented as a paratesticular tumor immediately after birth. PMID- 3352045 TI - Primary epithelial tumors of the bladder in children. AB - Epithelial tumors of the bladder in children are extremely rare and recurrences are even more unusual. We report 3 cases of which 2 had recurrence. ABO(H) antigens were negative in 1 case and they were mildly positive in the other. Although the current opinion is that epithelial tumors in children are benign and single, with a low incidence of malignancy, 3 other pediatric cases of epithelial tumor recurrence have been reported in the literature. Therefore, we wish to emphasize the importance of long-term and careful followup of these patients, since further recurrences are possible. PMID- 3352047 TI - Splenic gonadal fusion. AB - Splenic gonadal fusion is a rare anomaly that is frequently associated with skeletal abnormalities. Although rare, this entity should be considered in the differential diagnosis of scrotal masses in children. Routine frozen section prevents unnecessary orchiectomy. We describe a child with limb anomalies in whom splenic gonadal fusion presented as an incarcerated inguinal hernia. PMID- 3352048 TI - Intracavernous injection of vasoactive drugs after radical prostatectomy. PMID- 3352049 TI - The acquired immunodeficiency syndrome: prudent precautions for the practicing urologist. PMID- 3352051 TI - Treatment of unusual Kock pouch urinary calculi with extracorporeal shock wave lithotripsy. AB - Since the establishment of extracorporeal shock wave lithotripsy for the treatment of upper urinary tract calculi, further potential applications have been explored. We report the successful use of extracorporeal shock wave lithotripsy for the treatment of obstructive calculi on staples within the afferent nipple of a Kock pouch ureteroileal urinary diversion. PMID- 3352050 TI - Endopyelopyelotomy: percutaneous surgery for ureteropelvic junction obstruction in a bifid pelvis: further experience. AB - A patient with a bifid pelvis and ureteropelvic junction obstruction of the lower system was managed successfully by endopyelopyelotomy. This percutaneous procedure consists of creation of an internal fistula between the 2 pelves by incision of the intervening tissue with an optical urethrotome. This procedure provided a satisfactory and reproducible result. PMID- 3352053 TI - Corynebacterium-induced cystitis with mucosal incrustations. AB - Alkaline-incrusted cystitis is a rare condition that was first described more than 70 years ago. Since then few cases have been reported. To our knowledge, we report the second such case in the literature in which Corynebacterium D2 was considered as the causative factor of incrusted cystitis. PMID- 3352052 TI - Bilateral organ-limited amyloidosis of the distal ureter associated with osseous metaplasia and radiographic calcification. AB - We report a case of organ-limited amyloidosis of the distal portion of both ureters in which bilateral osseous metaplasia was present as well as radiographic evidence of ureteral wall calcification. This case represents the twenty-eighth report of localized ureteral amyloidosis and the fourth report with bilateral involvement. PMID- 3352054 TI - Perineal urethrocutaneous fistula complicating ischiectomy. AB - The role of ischiectomy for the repair and/or prevention of ischial ulcers is controversial. We report a rare complication of a perineal urethrocutaneous fistula following ischiectomy and flap closure to repair an ischial ulcer. This complication and its management are reviewed. PMID- 3352055 TI - Malignant melanoma of penis. AB - We report a case of malignant melanoma of the penis. Appropriate staging of these rare cancers is discussed in light of current views of the biology of malignant melanoma arising at other skin sites, and the implications of Breslow thickness for management are considered. There is no good evidence in the literature that extirpation of the entire penis offers the only hope of cure for stage I penile melanoma. PMID- 3352056 TI - Adenomatoid tumor of testicular tunica albuginea mimicking testicular carcinoma. AB - Adenomatoid tumors are an uncommon neoplasm of the paratesticular tissues, with the majority of the reported cases involving the epididymis. A case is reported of an adenomatoid tumor of the testicular tunica albuginea that masqueraded as testicular carcinoma. PMID- 3352057 TI - Pseudomyxoma peritonei presenting as a scrotal mass. AB - Pseudomyxoma peritonei may occur after intraperitoneal rupture of a mucinous adenocarcinoma. The liberated cells produce copious amounts of mucus, which mimics ascites. With the improved technology of computerized tomography and ultrasound, many of these cases are now being diagnosed preoperatively. Surgical debulking is the preferred therapy, while the role of chemotherapy and radiotherapy remains debatable. We report a case of pseudomyxoma peritonei presenting as a scrotal mass that was diagnosed preoperatively. PMID- 3352058 TI - Pyelo-choledochal fistula accompanying operative cholangiography. AB - Fistulous communications between the biliary system and the urinary tract are encountered infrequently and, routinely, they are associated with operative dissections involving both systems. We report a case of opacification of the right renal collecting system during cholangiography following uneventful cholecystectomy. Prompt spontaneous resolution was verified by subsequent excretory urography. PMID- 3352060 TI - Effects of granuloma formation at site of vasovasostomy. AB - Spermatic granulomas forming after vasectomy reversal have been thought to mechanically compromise the anastomosis. We have studied the physiologic effects of vasectomy and vasovasostomy in rats. Following delayed microsurgical vasovasostomy, fluid flow through the anastomosis and cauda epididymidal hydrostatic pressure are not significantly different in tracts that form, or do not form, sperm granulomas at the anastomosis. Given a properly performed microsurgical vasectomy reversal, a sperm granuloma arising from a small leak does not appear to mechanically compromise the anastomosis in the rat. Fertility after vasovasostomy is not significantly reduced in rats with granulomas. PMID- 3352059 TI - Local suppressive effect of clonidine on penile erection in the dog. AB - Dogs, 8.5 to 10 kg. in weight, were anesthetized with sodium pentobarbital (35 mg./kg.), intraperitoneally. Penile erection as indicated by an increase in the intracorporal pressure (ICP-increase) was produced by electrical stimulation of the right cavernous nerves. Drugs were administered into the internal pudendal artery (IPA) and femoral vein. A low dose (0.2 to 0.4 microgram/kg.) of clonidine, an alpha 2 adrenoceptor agonist, which could not affect either ICP or systemic arterial pressure (SAP) through an intravenous route, did suppress the ICP-increase markedly via direct injection into the IPA which supplies the penile blood flow. By intra-IPA injection, yohimbine (2.5 micrograms/kg.), an alpha 2 adrenoceptor antagonist, remarkably restored the ICP to the erection state. By intravenous injection, clonidine at a dose of 1.6 to 3.2 micrograms/kg. also profoundly reduced the ICP-increase, but only negligibly lowered the SAP. The IPA blood flow (IPAF) decreased coincidentally when the ICP-increase was effectively reduced by either intravenous or intra-IPA injection of clonidine. These findings suggest clonidine could act locally in the penile structure to suppress penile erection, possibly resulting from a penile vasoconstriction involving alpha 2 adrenoceptor. Whether this vasoconstriction is caused by a direct alpha 2 stimulating effect on the vascular smooth muscle or by an alpha 2 presynaptic inhibition of the vasodilator nerve (cavernous nerve) endings has been discussed. PMID- 3352062 TI - Anatomical study of the infra-montanal urethra in man. AB - Five samples infra-montanal prostatic urethra fixed in formalin and stored in liquid nitrogen at -30C were examined histologically. The results of this study demonstrated that muscle fibres of the striated sphincter extend as far as the level of the verumontanum. The proportion of rapid and slow striated fibres was identical. These striated fibres were mixed with smooth muscle fibres of the urethra. The density of innervation of this muscular tunic was found to increase closer to the striated sphincter; it is composed of equal numbers of adrenergic and cholinergic fibres. PMID- 3352061 TI - Measurement of multidrug-resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrinsic drug resistance. AB - We measured the levels of messenger RNA of the human multidrug-resistance gene (MDR1) in 25 urogenital tumors before chemotherapy. Many of the renal cell carcinomas continued to express MDR1 gene at high levels, reflecting the increased expression of MDR1 RNA in normal kidneys. In other urogenital tumors, the MDR1 RNA levels were low reflecting low MDR1 RNA levels in normal bladder, prostate and testis. For comparative purposes, we performed in vitro chemosensitivity testing on many tumor samples using soft agar culture techniques. Vinblastine sensitivity in vitro inversely correlated with MDR1 RNA levels (p less than 0.01). Moreover, mean sensitivity of seven renal cell carcinomas to vinblastin was significantly lower than that of the other seven cancers (p less than 0.05). As for doxorubicin, mean sensitivity of six renal cell carcinomas was lower than the others (p less than 0.1). These results suggest that the high MDR1 RNA levels in renal cell carcinomas are associated with intrinsic multidrug-resistance. PMID- 3352063 TI - A new approach to the study of urinary macromolecules as a participant in calcium oxalate crystallization. AB - Despite intense investigation, the relationship of urinary proteins to urinary stone matrix formation remains poorly understood. In an attempt to gain more information regarding this interaction, the binding of urinary proteins to calcium oxalate crystals formed in urine in vitro was studied. 0.1 M calcium chloride and 0.1 M sodium oxalate were added to an aliquot of urine collected from five non-infected, non-stone forming males. The resulting calcium oxalate crystals were centrifuged and the pellet demineralized with 5% EDTA. Gel filtration chromatography was used to isolate the protein fraction from the urine samples before and after crystallization of calcium oxalate. The proteins recovered from the crystals and urine were separated by two-dimensional polyacrylamide gel electrophoresis. Many, but not all of the urinary proteins were bound by the crystals. Albumin, seen to the most abundant urinary protein, was absent or markedly diminished in all instances, and the second most abundant urinary protein, PC-30, became the predominant protein component of the crystals. An unidentified protein with approximate molecular weight of 22,000 daltons and isoelectric point of 6.4 was highly concentrated by the crystals even when undetected in the urine. The study suggests that the binding of urinary proteins to calcium oxalate crystals formed in urine in vitro is not a random event but rather a selective phenomenon. PMID- 3352064 TI - AUA eighty-third annual meeting. American Urological Association, Inc. June 3-7, 1988, Boston. Abstracts. PMID- 3352065 TI - Diffuse arterial narrowing as a result of intimal proliferation: a delayed complication of embolectomy with the Fogarty balloon catheter. AB - Most complications of embolectomy with the Fogarty balloon catheter are recognized early and have received ample attention in the surgical and radiologic literature. However, the delayed complication of diffuse arterial narrowing causing severe ischemia has received little emphasis, perhaps because follow-up arteriography is not always performed. This report describes five patients--women 43 to 62 years of age--with progressive leg ischemia discovered 2 to 4 months after embolectomy with the balloon catheter. Angiography showed a characteristic pattern of severe, smooth narrowing of that portion of the artery in which balloon embolectomy was performed. Pathologic examination of arterial specimens, available in two of the five patients, revealed marked intimal cellular proliferation, which narrowed the arteries severely without evidence of thrombosis, significant atheromatosis, or active arteritis. The cause appears to be intimal damage by the balloon. Embolectomy with the balloon catheter should be done especially carefully in relatively young women. PMID- 3352066 TI - Early myointimal hyperplasia after balloon catheter embolectomy: effect of shear forces and multiple withdrawals. AB - Arterial stenosis occurring after balloon catheter embolectomy may be caused by myointimal hyperplasia (MIH). This study investigated the effects of shear force and repeated catheter withdrawals on the development of MIH after embolectomy. The procedures were performed in the common carotid and common femoral arteries of 18 anesthetized dogs. During catheter withdrawal, the balloons were filled gradually to produce shear forces rising smoothly from 50 to 200 gm. Four weeks after embolectomy, the vessels were perfusion-fixed in situ with 2% glutaraldehyde and were excised. The thickness and circumferential extent of MIH were measured in cross sections from segments of the vessels exposed to shear forces of 50, 100, and 200 gm. Sixty-nine of 72 arteries remained patent. Low shear force (50 gm) consistently elicited less MIH than did higher shear forces (p less than 0.05). At each level of shear force, repeated withdrawals resulted in greater circumferential extent of MIH than did single withdrawals (p less than 0.005). Although clinically it usually is necessary to perform multiple passes during balloon embolectomy, these data suggest that, in humans, attempts should be made to perform a minimal number of catheter withdrawals at low shear force to minimize the subsequent development of MIH. PMID- 3352067 TI - Transcutaneous oxygen and carbon dioxide pressure monitoring to determine severity of limb ischemia and to predict surgical outcome. AB - Transcutaneous oxygen and carbon dioxide pressure (PO2 and PCO2) foot monitoring was compared with ankle Doppler-derived systolic pressure regarding their respective abilities to discriminate the severity of limb ischemia before vascular reconstruction and to predict surgical outcome early in the postoperative period. Transcutaneous PO2 (tcPCO2), foot-chest tcPO2 index, transcutaneous PCO2 (tcPCO2), foot tcPO2/tcPCO2 index (tcPO2/tcPCO2), ankle Doppler systolic pressure (AP), and ankle-brachial pressure index (ABI) were determined in 89 revascularized limbs. The measurement of tcPO2 and foot-chest tcPO2 was found to be more sensitive to degrees of severity of limb ischemia and more closely associated with the outcome of revascularization than AP and ABI. TcPCO2 and tcPO2/tcPCO2 were not useful in assessment of the vascular patient undergoing reconstructive surgery. Before operation, tcPO2 less than or equal to 22 torr and foot-chest tcPO2 less than or equal to 0.46 indicate severe limb ischemia requiring urgent revascularization. After operation, tcPO2 less than or equal to 22 torr and foot-chest tcPO2 index less than or equal to 0.53 indicate that revascularization is likely to fail. We conclude that tcPO2 monitoring, as a metabolic test of actual tissue perfusion, is a more reliable indicator of preoperative limb ischemia and postoperative outcome of revascularization than hemodynamic, Doppler-derived pressure tests. PMID- 3352068 TI - Bacterial infectibility of chronically implanted endothelial cell-seeded expanded polytetrafluoroethylene vascular grafts. AB - Vascular prosthetic grafts become more resistant to infection as the interval between implantation and bacteremic challenge increases. Endothelial cell (EC) seeding of such grafts has been shown to improve measurably their ability to resist a bacteremic challenge several weeks after implantation, presumably by reducing the amount of thrombus-free area (TFA) on their luminal surface. However, no investigators have reported the impact of EC seeding on the ability of chronically implanted vascular prostheses to resist a late bacteremic challenge. Bilateral common carotid interposition grafts were placed in 15 adult mongrel dogs with a 4 mm internal diameter, experimental, expanded polytetrafluoroethylene (ePTFE) prosthesis. One animal died shortly after operation and the grafts in two dogs thrombosed, thereby leaving 12 animals with at least one patent graft for subsequent study. At a mean interval of 45 weeks after implantation, five dogs (seven patent grafts) were challenged with an intravenous infusion of 3 X 10(8) radiolabeled Staphylococcus aureus; bacterial adherence and the TFA of the graft's luminal surface were determined for each of the patent grafts. There was no statistically significant difference in bacterial adherence or TFA between EC-seeded and control grafts. At a mean interval of 53 weeks after implantation, the remaining seven dogs (14 patent grafts) received a similar bacterial infusion and the animals were allowed to recover. Five days later, the grafts were harvested and cultured. Once again, there was no significant difference in the infectibility of EC-seeded vs. control grafts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352069 TI - Extended reconstruction rate for limb salvage with intraoperative prereconstruction angiography. AB - A prospective study was performed between May 1982 and March 1987 to assess the value of intraoperative prereconstruction angiography (IPA) in limb salvage. Eligibility was limited to patients with rest pain, ischemic ulcers, or gangrene limited to the toes: only candidates for infrapopliteal bypass were included. Seventy-eight such patients were examined with preoperative angiography. Delayed films, selective catheterization, reactive hyperemia, or vasodilators were used routinely. In only 11 of 78 patients (14%) was the runoff adequately visualized, demonstrating the tibial vessels and the pedal arch. The remaining 67 patients (86%) (with nonreconstructable disease by currently accepted outflow criteria) had surgical exposure of a tibial or pedal artery for IPA. In 56 of these patients (84%) good runoff was demonstrated and bypass was performed. The reconstruction rate was 86% (67 of 78 patients), significantly higher than the 33% rate reported by others. The operative mortality rate was 2.8% (2 of 78 patients). We concluded that in severe ischemia preoperative angiography is often inadequate in demonstrating runoff, even with adjunctive measures to dilate the outflow vessels. IPA through the tibial and pedal vessels eliminates all of the proximal vascular resistance, thereby providing a "completion angiogram" before reconstruction. This in turn extends reconstructability to many patients who would otherwise undergo primary amputation. PMID- 3352071 TI - Treatment of a case of thromboembolism resulting from thoracic outlet syndrome with intra-arterial urokinase infusion. AB - A 36-year-old man with thoracic outlet syndrome, admitted to the hospital with digital ischemia from subclavian artery thrombosis and distal embolization, was given intra-arterial urokinase. Thrombus in the subclavian artery was lysed successfully and peripheral emboli were partially cleared, resulting in relief of digital symptoms. Although surgical decompression and vascular reconstruction at the thoracic outlet may be necessary, this technique provides a means of recanalizing small distal vessels. PMID- 3352072 TI - The management of steal syndrome occurring after access for dialysis. PMID- 3352070 TI - Biochemical and histopathologic comparison between blood and saline storage of canine veins. AB - Patency of vein grafts may be influenced by the medium in which they are stored temporarily. We compared saline solution vs blood on prostanoid production and maintenance of endothelium in canine veins after 1 hour of storage at 23 degrees C with 0.2 mg/ml of papaverine. Spontaneous and arachidonate-stimulated prostaglandin levels were measured by radioimmunoassay. Endothelial integrity was analyzed by light and electron microscopy. Prostaglandin production in blood vs that in saline solution was 1821 +/- 1264 and 1259 +/- 719 pg/cm2/min at control and 6705 +/- 3702 vs 6264 +/- 3409 pg/cm2/min, respectively, after stimulation. There were no statistically significant differences between the groups at any time point. Thromboxane levels were also indistinguishable between groups. Microscopy revealed 70% endothelial loss in blood vs 95% for saline solution. We conclude that endothelial preservation is enhanced by blood storage, that the medial layer produces substantial amounts of prostacyclin, and that additional storage solutions need to be investigated. PMID- 3352073 TI - A simplified technique for percutaneous insertion of permanent vascular access catheters in patients requiring chronic hemodialysis. PMID- 3352074 TI - A technique for visualization of an anastomosis during flushing. PMID- 3352075 TI - Evaluation of a proposed standard reporting system for preoperative angiograms in infrainguinal bypass procedures: angiographic correlates of measured runoff resistance. PMID- 3352076 TI - External carotid revascularization. PMID- 3352077 TI - Heparinization reduces endothelial permeability and hydrogen ion accumulation in a canine skeletal muscle ischemia-reperfusion model. AB - Skeletal muscle injury after revascularization (ischemia-reperfusion) continues to be a major clinical problem. Although heparinization has been recommended, its action in an experimental model of I-R has not been evaluated. We investigated the ability of heparinization to decrease I-R injury in 10 anesthetized dogs (nonheparinized, n = 5; heparinized, n = 5), subjecting one gracilis muscle to 6 hours of ischemia followed by 1 hour of reperfusion while the identically prepared contralateral muscle served as a nonischemic control. Skeletal muscle infarction was determined by Tc-PYP uptake. Endothelial permeability was quantified by measurement of skeletal muscle 125I-Alb activity after intravenous injection. Interstitial hydrogen ion (H+) accumulation was determined by a miniature pH electrode inserted into the gracilis muscle. Isotopic activities from the ischemic muscle were calculated as a percentage of the contralateral nonischemic muscle (mean +/- SEM). Nonheparinized ischemic muscles had an increase in the activities of Tc-PYP and 125I-Alb of 684% +/- 149% and 742% +/- 130%, which were reduced to 218% +/- 54% and 378% +/- 85% by heparinization, respectively (p less than 0.05). During ischemia, the nonheparinized muscles accumulated 1223 +/- 121 nmol of H+ compared with 785 +/- 95 nmol in the heparinized animals (p less than 0.01). This significant reduction in I-R injury may be causally related to diminished endothelial permeability and H+ accumulation. PMID- 3352079 TI - Growth factor production by polytetrafluoroethylene vascular grafts. AB - In earlier studies, we have shown that porous (60 micron internodal distance) PTFE grafts develop a complete endothelial layer 2 weeks after being implanted in baboons. Subsequently, the intima of the graft thickens on account of SMC proliferation only where an overlying endothelial layer is present. SMCs in normal endothelialized artery proximal and distal to the graft show no detectable proliferation. The purpose of this study was to investigate the possibility that growth factors released from the graft endothelium or SMCs regulate SMC proliferation. PTFE grafts (4 mm I.D., 60 micron internodal distance) were placed in the aortoiliac circulation of baboons and removed at 2 weeks. The grafts were perfused ex vivo with tissue culture medium (Ham's F12 + 25 mmol/L HEPES and 2% calf plasma-derived serum) at 2.5 ml/hr for 5 hours. Perfused native carotid, aorta, and femoral arteries served as controls. After this period of perfusion, graft and arterial endothelium was intact as shown by scanning electron microscopy. The mitogenic activity (thymidine incorporation) of the perfusates was measured in an assay with quiescent 3T3 cells and baboon aortic SMCs and corrected for the surface area of the perfused vessels. These studies demonstrated markedly increased mitogenic activity in the perfusates of grafts compared with perfusates of native vessels. These results provide support for the hypothesis that the vascular wall cells in healing grafts can produce factors that regulate smooth muscle cell growth. PMID- 3352078 TI - Kinetics of endothelial cell-surface attachment forces. AB - Physical and biochemical forces exist that are necessary for the persistent attachment and function of ECs on native and prosthetic blood vessels. The optimization of conditions that permit regeneration of these attachment forces may allow rapid establishment of a durable, biocompatible EC monolayer. We examined the effects of three major factors, protein substrate, EC incubation time, and shear stress, on the attachment kinetics of human adult ECs to two different polymers. ECs were incubated up to 30 minutes on polymers (PS or PET) coated with extracellular matrix proteins: collagen I/III, fibronectin, collagen IV/V, laminin, gelatin, or saline control. After incubation, continued attachment in the presence of shear stress (created in a rotating disc device) between zero and 90 dynes/cm2 for 30 minutes was evaluated. Maximal adherence was observed on all substrates by 30 minutes. Therefore, after a 30-minute incubation, the percentage of cells attached (postshear ECs/preshear ECs/preshear ECs X 100) was measured as a function of shear stress. ECs attached to a matrix of fibronectin or collagen I/III demonstrated shear-resistant adherence after as little as 5 minutes of static incubation before initial shear exposure. By 30 minutes, more than 90% of the ECs on both matrices demonstrated the ability to remain attached in the presence of 90 dynes/cm2 of shear stress. We conclude that forces that attach ECs to surfaces are affected by temporal factors (incubation time) and substrate composition and may be quantified with a defined shear stress detachment assay. Understanding and manipulating these temporal physiochemical parameters should allow one to re-create an optimal EC monolayer on a blood contacting surface. PMID- 3352080 TI - Visceral helminth communities of an insular population of feral swine. AB - Nine species of helminths, all nematodes, were recovered from the viscera of 48 feral swine (Sus scrofa) from Cumberland Island, Georgia. Both the overdispersed frequency distributions and the abundances of the four common species of helminths (Stephanurus dentatus, Metastrongylus apri, M. pudendotectus and Gongylonema pulchrum) did not vary significantly across the main and interactive effects of host sex and/or seasons. Whether or not the present low population densities of feral swine on Cumberland Island has influenced the pattern of fluctuations in abundances of helminth species across seasons as often observed in helminth communities from other hosts was not resolved. The apparent recent decline in prevalences and abundances, and the loss of certain species from the helminth communities of feral swine on the island may be explained partially by the decreasing transmission potentials of direct life cycle species caused by a recent marked reduction of numbers of individuals in the host population. Conversely, the apparent increased prevalence and abundance of three species of helminths (S. dentatus, M. apri and M. pudendotectus) may be related to their common utilization of earthworms as paratenic or intermediate hosts. Gongylonema pulchrum was the only helminth in which abundances seemed to remain unchanged. This was the only species that was not strictly host specific to feral swine. We found no evidence that helminth infections were responsible for morbidity or mortality in this feral swine population. PMID- 3352081 TI - Experimental anaplasmosis in mule deer: persistence of infection of Anaplasma marginale and susceptibility to A. ovis. AB - An experimental Anaplasma marginale infection was induced in a splenectomized mule deer (Odocoileus hemionus hemionus) which persisted subclinically at least 376 days as detected by subinoculation into susceptible cattle. Anaplasma ovis was experimentally transmitted from sheep to a splenectomized and a spleen-intact mule deer, and back to sheep. The pathogenesis in deer was very similar to that seen in sheep using ovine blood inoculations. PMID- 3352082 TI - Skull deformity in a herring gull chick (Larus argentatus). AB - A skull deformity resulting in death of a herring gull chick (Larus argentatus) is described in detail. The bones of the skull and upper jaw were twisted, asymmetrical and of unusual size or absent. The lower jaw had an almost "spoon like" external appearance and lacked normal articular surfaces. PMID- 3352083 TI - An internal X-cell pseudotumor in a black croaker (Cheilotrema saturnum). AB - Cells closely resembling X-cells were the primary cellular component of a large pseudotumor in the viscera of a black croaker (Cheilotrema saturnum). The fish was captured in coastal waters off San Diego, California and was maintained at the Scripps Aquarium. After 2 years in captivity the fish exhibited extreme abdominal swelling due to a visceral mass, which weighed approximately one-fifth the total body weight. The cells associated with the pseudotumor were identified as X-cells due to their great variability in size, vesicular nuclei which stained negative for DNA and their formation of a pseudotumor. This is the first report of an X-cell pseudotumor in the visceral cavity. We agree with the hypothesis that the X-cell is a protozoan, and the description here of X-cells in a visceral pseudotumor in a fish of the family Sciaenidae associates an additional type of lesion with this enigmatic parasite. PMID- 3352084 TI - Severed intestine in channel catfish. AB - Six cases of severed intestines in farm-raised channel catfish were examined at fish disease diagnostic laboratories in Mississippi and Alabama. This condition has not been reported previously in fish. Affected fish had a 4-7-cm-long intestinal section (hyperemic where it was severed) attached to the stomach. The remainder of the intestine was completely missing in all six cases except for a 1 1.5-cm section of intestine prolapsed from the anus in fish from three of the cases. Ischemia, autodigestion following intussusception, or intestinal epithelium degradation are suggested as possible etiologies for this condition. PMID- 3352085 TI - Experimental Cryptosporidium parvum infections in opossums (Didelphis virginiana). AB - Five nursing opossums (Didelphis virginiana) were each inoculated with 5 x 10(6) Cryptosporidium parvum oocysts of calf origin. Following inoculation, endogenous stages of C. parvum were observed in the ileum, cecum, and colon of these opossums. Two of three noninoculated pouch mates acquired infections during the study based on examinations of feces and tissue sections of all eight opossums. Mild diarrhea was observed in four of seven opossums harboring C. parvum, although none died as a result of the infection. Under the conditions of this study, C. parvum appeared to be only mildly pathogenic for opossums. PMID- 3352086 TI - Mesocestoides sp. tetrathyridia (Cestoidea: Cyclophyllidea) in the iguanid lizards, Cophosaurus texanus texanus and Sceloporus olivaceous, from Texas. AB - New host records are reported for Mesocestoides sp. tetrathyridia in two species of iguanid lizards (Cophosaurus texanus and Sceloporus olivaceous) from Texas. Tetrathyridia were found free within the body cavity or encapsulated in the liver of the hosts. Prevalence of infection was generally low, with intensities ranging from 90 to over 200 tetrathyridia per host. In addition, a summary of North American lizard species reported as hosts of Mesocestoides sp. tetrathyridia is presented. PMID- 3352087 TI - Dirofilaria immitis in the dingo (Canis familiaris dingo) in a tropical region of the Northern Territory, Australia. AB - The heart and lungs from 32 adult dingoes (Canis familiaris dingo) were examined for canine heartworm (Dirofilaria immitis) infection. Eighteen of 32 (56%) samples were infected, with intensity of infection ranging from 1 to 31 worms per animal. Seven of 18 (39%) infections were single sex infections. Large numbers of circulating microfilariae were present in blood from all dingoes infected with both sexes of worms. PMID- 3352088 TI - Notes on parasites in penguins (Spheniscidae) and petrels (Procellariidae) in the Antarctic and Sub-antarctic. AB - Blood smears were examined from 143 penguins of four species (Aptenodytes patagonicus, Eudyptes chrysolophus, E. schlegeli, and Pygoscelis gentoo) from Sub antarctic Macquarie Island and Heard Island. No blood parasites were reported. The vectors of Hepatozoon albatrossi (reported from three species of albatross) are probably shared by penguins, and it is suggested that the latter are not susceptible to infection with this protozoan. Cestodes of the genus Tetrabothrius were present in large numbers in the intestines of 17 Antarctic petrels (Thalassoica antarctica), and evidence is presented indicating that euphausiid crustaceans may be intermediate hosts. PMID- 3352089 TI - Blackbuck antelope (Antilope cervicapra), a new host for Psoroptes cuniculi (Acari: Psoroptidae). AB - Information was requested on the cause of extensive lesions and death of a blackbuck antelope (Antilope cervicapra). Psoroptes cuniculi, the ear mite of domestic rabbits, was identified as the cause of the lesions. Death of the antelope was attributed to a secondary bacterial infection. This is the first report of P. cuniculi on blackbuck antelope. The potential impact of these mites on blackbuck antelope and other exotics in Texas is unknown. PMID- 3352090 TI - Actinobacillosis in free-ranging snowshoe hares (Lepus americanus) from Alaska. AB - Actinobacillus capsulatus was isolated from lung, liver, and/or spleen tissue of three snowshoe hares (Lepus americanus) in Alaska. This is the first report of the isolation of this bacterium from free-ranging hares. Actinobacillus capsulatus may have a negative impact on the population density of hares. PMID- 3352091 TI - Hematology, intestinal parasites, and selected disease antibodies from a population of bobcats (Felis rufus) in central Arkansas. AB - Eight bobcats with adjoining or overlapping home ranges were examined. Hematological values were within previously reported ranges. Six bobcats demonstrated antibody titers to Toxoplasma gondii. Isospora spp., Taenia taeniaeformis, Spirometra mansoides, Physoloptera rara, Toxocara cati, Strongyloides spp., Trichurus spp., Capillaria spp., and Ancyclostoma spp. were found also in the animals examined. The mean number of parasite species per host was 4.1. All bobcats tested negative for serum antibodies to Rocky Mountain spotted fever (Rickettsia rickettsii). Two bobcats had titers less than or equal to 1:20 for tularemia (Francisiella tularensis), and two were positive for leptospirosis (Leptospira spp.). PMID- 3352092 TI - Carcass temperature in relation to botulism. PMID- 3352093 TI - Characteristics of Yersinia spp. isolated from wild and zoo animals. AB - Thirteen strains of Yersinia spp. were isolated at the Rome zoo and at Castelporziano, a game preserve near Rome. The strains were tested for calcium dependency, autoagglutination, heat-stable toxin production, 50% minimum lethal dose in mice (LD50), pyrazinamidase activity and content of plasmids by electrophoresis in agarose gel. The former three tests were negative for all strains, the LD50 was always greater than or equal to 1 X 10(7.6) CFU/ml and pyrazinamidase activity was positive for all strains. Electrophoresis revealed the presence of two plasmids of 27 and 66 megadaltons (MDa) in the two strains of Y. enterocolitica of serotype 027 isolated from animals in the zoo. The two strains of the same species and serotype, isolated from wild animals harboured a 42-MDa plasmid. A small plasmid of 2 MDa was found in two strains of Y. enterocolitica of serotype 07.8 from two subsequent samples of a zoo animal. PMID- 3352095 TI - Toxic effects of natural saline waters on mallard ducklings. AB - Water from 10 saline wetlands in Saskatchewan was provided as drinking water for 1-day-old mallards (Anas platyrhynchos). Ducklings given water with conductivity from 3,750 to 7,490 microns hos/cm grew as well as birds on fresh water during a 14-day trial, but birds given water with conductivity of 4,000 microns hos/cm grew poorly during the last 2 wk of a 28-day trial. Ducklings given water with conductivity of 7,720 micron hos/cm grew poorly during a 14-day trial. Six of 10 ducklings given water with conductivity of 20,000 microns hos/cm died, and only two of nine ducklings given water with conductivity of 21,500 microns hos/cm survived 14 days. Survivors were much smaller than controls and had many abnormalities. All ducklings given water with conductivity of 35,000 and 67,000 microns hos/cm died within 60 and 30 hr, respectively. The results indicate that ducklings hatched on many saline wetlands will suffer toxic effects unless they are able to find a source of fresh water shortly after hatching. PMID- 3352094 TI - Effects of sodium and magnesium sulfate in drinking water on mallard ducklings. AB - One-day-old mallard (Anas platyrhynchos) ducklings were given drinking water for up to 28 days that contained concentrations of sodium and/or magnesium similar to those found in saline wetlands. Growth, tissue development, and biochemical characteristics of these ducklings were compared to those reared on fresh water. Much of the ingested salt was excreted by passage of voluminous fluid excreta. This effect occurred in birds given water with as little as 500 ppm Mg or 1,000 ppm Na. The supraorbital salt gland was active within 4 days in ducklings drinking water containing greater than or equal to 1,500 ppm of Na. Feather growth was decreased in ducklings drinking water with greater than or equal to 1,500 ppm of either Na or Mg. Ducklings drinking water with 3,000 ppm of either ion, or 1,500 ppm of each, grew more slowly than control birds. Ducklings drinking water with 3,000 ppm of either Na or Mg had reduced thymus size and bone breaking strength. Those drinking water with 3,000 ppm of Mg, or 3,100 ppm Na and 1,300 ppm Mg also had less trabecular bone and enlarged adrenals. Birds drinking the latter water had an elevated concentration of Na and calcium, and a decreased concentration of phosphorus and chloride in their serum, and elevated plasma protein levels. Ducklings reared on fresh or slightly saline water adapted very poorly to an abrupt change to more saline water (specific conductivity = 15,250 microns hos/cm) at 14 days of age. These birds stopped eating, became inactive and some died within 3 days; survivors had many tissue and biochemical abnormalities at 20 days of age. The level of salinity in these trials was similar to that in "brackish" or "moderately saline" wetlands and lower than that previously found to have effects on growth and feathering of ducklings. Many of the sublethal effects were subtle and non-specific manifestations of stress, and would be difficult to detect in wild ducklings on saline wetlands. PMID- 3352096 TI - Brain cholinesterase activity of apparently normal wild birds. AB - Organophosphorus and carbamate pesticides are potent anticholinesterase substances that have killed large numbers of wild birds of various species. Cause of death is diagnosed by demonstration of depressed brain cholinesterase (ChE) activity in combination with chemical detection of anticholinesterase residue in the affected specimen. ChE depression is determined by comparison of the affected specimen to normal ChE activity for a sample of control specimens of the same species, but timely procurement of controls is not always possible. Therefore, a reference file of normal whole brain ChE activity is provided for 48 species of wild birds from North America representing 11 orders and 23 families for use as emergency substitutes in diagnosis of anticholinesterase poisoning. The ChE values, based on 83 sets of wild control specimens from across the United States, are reproducible provided the described procedures are duplicated. Overall, whole brain ChE activity varied nearly three-fold among the 48 species represented, but it was usually similar for closely related species. However, some species were statistically separable in most families and some species of the same genus differed as much as 50%. PMID- 3352098 TI - Bone morphometrics and tetracycline marking patterns in young growing American alligators (Alligator mississippiensis). AB - Nine young American alligators (Alligator mississippiensis) were injected at monthly intervals with tetracycline to determine the bone apposition rate and the resorption patterns over a 3-mo period. The periosteal apposition rate increased progressively over the 3-mo period from 2.99 microns/day to 5.94 microns/day. Endosteal apposition rate was much slower with incomplete tetracycline lines being observed on the endosteum. This suggests that most modeling-resorptive activities occur on the endosteal envelope. PMID- 3352097 TI - Concentrations of contaminants in muscle of the American alligator in Florida. AB - Samples of tail muscle from 32 American alligators (Alligator mississippiensis) in Florida were analyzed for contaminant concentrations to provide preliminary information on the potential public health hazard of meat consumption. Detectable levels were found for eight metals; copper, zinc, iron, chromium, mercury, lead, cadmium and arsenic. Mean residue was highest for mercury (geometric mean = 0.61 ppm). DDE, DDD, DDT, dieldrin, heptachlor epoxide, lindane, and PCB's were found. Mean residue concentrations were compared by lake. Alligators appeared to be suitable monitors of environmental pollution. Concentrations of contaminants found in these animals probably pose little threat to public health. However, recommendations must await analysis of larger sample sizes and information on amount and frequency of meat consumption. Alligators killed for human consumption should continue to be monitored for contaminant residues. PMID- 3352099 TI - Hematology and serum biochemistry of captive swift foxes (Vulpes velox). AB - Blood samples were taken from 23 swift foxes (Vulpes velox) which were to be used in a reintroduction program. The foxes originated from two different captive breeding programs: one at the Calgary Zoo (CZ) and one at the Wildlife Reserve of Western Canada (WRWC). Several differences between swift fox and domestic canine hematology were seen, including an increased number of smaller red blood cells and lower absolute leukocyte counts in swift foxes. Serum glutamic pyruvic transaminase was higher than in the domestic canine normal range while serum creatinine values were lower. Hemoglobin, serum potassium, total protein, globulin in the two groups (CZ and WRWC) were statistically different as were male versus female mean corpuscular volume values. PMID- 3352100 TI - Response of urinary hydroxyproline to dietary protein and fasting in white-tailed deer. AB - The effects of dietary protein, fasting, and refeeding on urinary hydroxyproline of nine captive female white-tailed deer (Odocoileus virginianus) were examined from 23 February to 3 May 1984 in northern Minnesota. In the fasted group, mean hydroxyproline:creatinine (OHP:C) was greater (P less than 0.05) at week 4 compared to baseline at week 0. Between fasted deer and deer fed high protein high energy (HPHE) and low protein-high energy (LPHE) diets, no difference in OHP:C ratios was detected during the initial 4 wk of the study. Urinary OHP:C ratios were significantly (P less than 0.05) greater in the fasted group during refeeding, concomitant with greater feed consumption and weight gain. There was also a significant (P less than 0.02) time effect in the fasted-refed group; OHP:C ratios increased during these two phases of the study. There was no difference between the HPHE and LPHE fed deer in renal OHP excretion. However, mean OHP:C ratios in yearlings (16.8 +/- 2.2) were greater (P less than 0.001) than in the adults (7.5 +/- 1.2) of those groups, indicating a higher collagen turnover rate. Urinary OHP:C shows potential as an indicator of growth and starvation, and the data presented may serve as reference values. PMID- 3352101 TI - Trichomoniasis in free-living goshawks (Accipiter gentilis gentilis) from Great Britain. AB - The goshawk Accipiter gentilis has recently been reintroduced into parts of Great Britain. During the course of a study of one population, lesions of stomatitis were observed in 14 young from five broods and all the affected birds died. Postmortem examination of three birds revealed live Trichomonas gallinae in exudate from one, and histological findings consistent with a diagnosis of trichomoniasis were made in this and one other bird. It is suggested that trichomoniasis may be a significant mortality factor in goshawks from Britain. PMID- 3352102 TI - A piece of my mind. Le Mot Juste. PMID- 3352103 TI - A piece of my mind. Messages from afar. PMID- 3352104 TI - DNA fingerprints come to court. PMID- 3352105 TI - Three-dimensional magnetic resonance cardiac imaging shows initial promise. PMID- 3352106 TI - Presidential commission recommends campaign against drug abuse to help combat AIDS. PMID- 3352108 TI - Leads from the MMWR. Premature mortality by income level--Multnomah County, Oregon, 1976-1984. PMID- 3352107 TI - Spring's here; can end of present influenza season in United States be far behind? PMID- 3352109 TI - Leads from the MMWR. Mercury exposure in a high school laboratory--Connecticut. PMID- 3352110 TI - Leads from the MMWR. Self-reported hearing loss among workers potentially exposed to industrial noise--United States. PMID- 3352111 TI - Impact of the revised AIDS case definition on AIDS reporting in San Francisco. PMID- 3352112 TI - HIV transmission and childhood sexual abuse. PMID- 3352114 TI - The deprofessionalization of medicine. PMID- 3352113 TI - Caring for the poor. PMID- 3352115 TI - Toxicity of diethyltoluamide-containing insect repellents. PMID- 3352116 TI - 'Treatment IND' is an oxymoron. PMID- 3352117 TI - Patient-controlled analgesia. PMID- 3352119 TI - Anencephalic newborns as organ donors: a critique. PMID- 3352118 TI - Establishing the diagnosis of benign familial hematuria. The importance of examining the urine sediment of family members. AB - Patients with microscopic hematuria are generally referred for urologic investigation. We describe 30 patients with normal renal function referred to our clinic during the years 1970 through 1987 for evaluation of hematuria, usually microscopic, in whom prior urologic and radiological studies had failed to determine the cause of bleeding. Urinary sediment from the patients and first degree relatives revealed hemoglobin and red blood cell casts; the inheritance pattern was consistent with autosomal dominant transmission. During follow-up for up to 18 years, renal function remained normal, thus confirming the diagnosis of benign familial hematuria. Immunoglobulin A nephropathy and Alport's syndrome were less common than benign familial hematuria and could be differentiated from it by history, physical examination, and routine laboratory testing. Since benign familial hematuria is a common disorder in adults with hematuria and normal renal function, urinary sediment from patients and family members should be examined before extensive urologic and radiological procedures are performed. PMID- 3352120 TI - A piece of my mind. Unsung hero. PMID- 3352121 TI - Drug testing upheld, decried; physicians asked to help decide. PMID- 3352122 TI - Tobacco-and-health courtroom drama continues. PMID- 3352123 TI - When medical help really is far away... PMID- 3352124 TI - Does physical fitness of today's children foretell the shape of tomorrow's adult America? PMID- 3352125 TI - Projects demonstrate how to involve physicians in care of workers at risk of health impairment. PMID- 3352126 TI - Leads from the MMWR. Autopsy frequency--United States, 1980-1985. PMID- 3352127 TI - The selection of residents. PMID- 3352128 TI - Autologous blood donation. PMID- 3352129 TI - A physician's guide to adoption. PMID- 3352130 TI - Platelet utilization in a university hospital. AB - Two hundred forty-three patients received 22,717 U of platelets in our hospital during a three-month period. Those with hematologic diseases accounted for 43% of the patients but used 86% of the platelets. Sixty-eight percent of the transfusions were given to prevent bleeding and 32% were given to treat active bleeding. Ninety-two percent of therapeutic transfusions but only 22% of prophylactic transfusions met guidelines established by the Transfusion Therapeutics Committee of the University of Minnesota Hospital and Clinics, Minneapolis. However, 78% of prophylactic platelet transfusions that did not meet the guidelines involved patients with at least one clinical factor that their physicians believed placed them at an increased risk of bleeding. Following this analysis, the guidelines were modified and applied prospectively to requests for platelets. This resulted in a 14% decrease in the number of platelet units used during the following year. We conclude that published recommendations for platelet transfusions do not reflect the complex nature of many patients' conditions and that the use of guidelines developed by the medical staff can alter the use of platelet transfusions. PMID- 3352131 TI - Legionnaires' disease associated with a hospital water system. A five-year progress report on continuous hyperchlorination. AB - In 1981, sixteen cases of nosocomial legionellosis occurred among 456 patients admitted to a new hematology-oncology unit (35 per 1000 admissions). Monoclonal antibody typing and restriction endonuclease plasmid analysis identified a unique strain (09,04) of Legionella pneumophila serogroup 1 isolated from both patients and water outlets. Continuous hyperchlorination of the hot and cold water began in January 1982, and chlorine levels of 3 to 5 mg/L have been maintained most recently. Water samples have been consistently negative for Legionella for more than five years. Four sporadic cases of nosocomial legionellosis have occurred in the hematology-oncology unit during the same period (one per 1000 admissions) associated with a different strain of L pneumophila serogroup 1 (09,00). The environmental reservoir(s) of L pneumophila serogroup 1 in these cases has not been identified. Levels of trihalomethanes (potential carcinogens) were high (greater than 100 micrograms/L) when chlorine levels of hot water exceeded 4 mg/L. Some corrosion damage to the water distribution system has occurred: the average number of leaks per month increased steadily from zero in 1982 to 5.2 in 1986. The chlorinator installation costs were +75,800, and annual operation expenses were +12,500. Continuous hyperchlorination is a promising but still experimental technique for control of nosocomial legionellosis. In our experience, epidemic disease has been controlled, but sporadic cases have continued to occur. PMID- 3352133 TI - Guidelines for platelet transfusion. PMID- 3352132 TI - Preventing the heterosexual spread of AIDS. Are we giving our patients the best advice? PMID- 3352134 TI - Cascades, collusions, and conflicts in cardiology. PMID- 3352135 TI - A piece of my mind. Forgiveness. PMID- 3352136 TI - A piece of my mind. Listen to the picture. PMID- 3352137 TI - A piece of my mind. The mark of a survivor. PMID- 3352138 TI - A piece of my mind. Panic. PMID- 3352140 TI - A piece of my mind. An unexpected burden. PMID- 3352139 TI - A piece of mind. A piece of her heart. PMID- 3352141 TI - A piece of my mind. Charity, the media, and limited medical resources. PMID- 3352143 TI - [A more detailed discussion of bioethical considerations in nursing research]. PMID- 3352142 TI - Triple urogenital cancer in a patient with a history of heavy smoking who had been exposed to the Hiroshima atomic bomb explosion. AB - A survivor of the Hiroshima atomic bomb experienced triple cancer of the urogenital organs after a long history of heavy smoking. The cancers comprised a clear cell carcinoma of the right kidney, transitional cell carcinomas of the urinary bladder, left ureter and left renal pelvis, and adenocarcinoma of the prostate. PMID- 3352144 TI - [Basic concepts of nursing ethics and underlying philosophies]. PMID- 3352145 TI - [Ethical issues in nursing research]. PMID- 3352146 TI - [Contemporary Japanese culture and recent trends in ethical ideas]. PMID- 3352147 TI - [Ethical judgment and choice of actions]. PMID- 3352148 TI - [Overview of ethical issues and trends related to nursing research]. PMID- 3352149 TI - [Ethical problems and strategies for nursing research: basic concepts]. PMID- 3352150 TI - [Ethical problems of nursing research in Japan]. PMID- 3352151 TI - [Human rights committees]. PMID- 3352152 TI - Whatever became of charity? PMID- 3352153 TI - Physician's obligation to cooperate with third-party payors. PMID- 3352154 TI - Two double translocation families. PMID- 3352155 TI - Balloon dilatation therapy for calcific aortic stenosis in the elderly. PMID- 3352156 TI - A standard nomenclature for structures of the kidney. The Renal Commission of the International Union of Physiological Sciences (IUPS). PMID- 3352158 TI - Theophylline in rats during maintenance phase of post-ischemic acute renal failure. AB - We have shown previously that theophylline increases both renal plasma flow (RPF) and glomerular filtration rate (GFR) during the initiation phase of post-ischemic acute renal failure (ARF) in rats. The purpose of the present experiments was to determine the effects of theophylline during the maintenance phase of ARF, five days after initiation. Clearance techniques were used to measure renal function in a control group of pentobarbital anesthetized rats (group C) and in three experimental groups, five days after subjecting the left kidney to a thirty minute period of complete ischemia. Group SS received saline during both the ischemic episode and the clearance measurements; group ST received saline during ischemia and theophylline, acutely, during the clearance measurements; group TS received theophylline during ischemia and saline during the clearance measurements. In comparison with the values for the control group (group C), RPF and GFR of the post-ischemic left kidneys of group SS were approximately half normal. In groups ST and TS, RPF and GFR of the left kidneys were higher than in group SS. Collectively, these results demonstrate that pretreatment with theophylline during the initiation phase of ischemia-induced ARF leads to increased RPF and GFR during the maintenance phase, and that acute theophylline treatment during the maintenance phase acutely increases RPF and GFR. Since increases in GFR were associated with increases in RPF, and since theophylline is an adenosine receptor antagonist, these results are consistent with the hypothesis that adenosine-mediated hemodynamic changes play a pathogenic role in ischemia-induced ARF in rats. PMID- 3352157 TI - Glomerular size and charge selectivity in insulin-dependent diabetes mellitus. AB - The pathogenesis of clinical nephropathy in Type 1 (insulin-dependent) diabetes was investigated by measuring renal fractional clearances of albumin, total IgG, IgG4 and beta 2-microglobulin, four plasma proteins which differ in size and charge. Seventy patients and eleven control subjects were studied. In diabetic patients with normal urinary albumin excretion (less than 30 mg/24 hr), fractional IgG clearance was two to three times higher than in control subjects, whereas fractional clearance of the anionic plasma proteins IgG4 and albumin was similar to that of control subjects. These alterations indicate an increase in anionic pore charge within the glomerular basement membrane concomitant with an increase in either pore size or impairment of tubular reabsorption. Diabetic patients, whose urinary albumin excretion has started to rise (30 to 100 mg/24 hr), had unchanged fractional IgG compared to patients with normal albumin excretion, while fractional IgG4 and albumin clearances were increased three- to fourfold; indicating unchanged glomerular pore size, but a decrease in anionic pore charge. In patients demonstrating urinary albumin excretion of greater than 100 mg/24 hr fractional IgG clearance increased to the same extent as fractional albumin clearance, indicating an increase in large pore area. Fractional beta 2 microglobulin clearances were similar to that of control subjects in the different patient groups indicating unchanged tubular reabsorption of proteins. Thus, the increase in large pore area seen in patients with clinical nephropathy is preceded by loss of anionic charge in the glomerular basement membrane. It is likely that this loss of anionic charge is due to loss of heparan sulphate proteoglycan. PMID- 3352159 TI - In utero aminoglycosides-induced nephrotoxicity in rat neonates. AB - Pregnant Wistar females were treated with gentamicin (G), netilmicin (N) or amikacin (A) during two periods of pregnancy covering organogenesis and the beginning of nephrogenesis. Deliveries occurred normally. We studied functional effects--influence of sex, litter size, diuresis, creatinine clearance, G-kidney concentration, and kidney morphological alterations--in rat neonates on day 1 of life. After G and N, the creatinine clearance of the neonates was decreased according to the dosage given to the mother. Whatever the aminoglycoside, kidneys presented proximal tubular alterations (close to those observed in adults) at protonic microscopy and, with electron microscopy, some modifications of distal tubules and of mature and immature glomeruli. It is concluded that the developing kidney can be altered after treating pregnant mothers with aminoglycosides. This model of in utero-induced nephrotoxicity is dose-dependent. Mature and/or immature structures could be affected. The toxicity of the investigated antibiotics could be asserted as G greater than or equal to N greater than A. PMID- 3352160 TI - Improvement of growth and food utilization by human recombinant growth hormone in uremia. AB - We compared growth rate, food conversion ratio and morphology of the growth zone in female Sprague-Dawley rats with subtotal nephrectomy or sham operation. Both groups were either given vehicle or 1.4 IU/day recombinant human growth hormone (GH) by s.c. osmotic minipump, or 2.5 IU twice daily intraperitoneally for 14 or 20 days, respectively. Compared to uremic rats infused with vehicle, infusion of GH significantly (P less than 0.01) improved growth; that is, it increased gain of weight (delta 27.0 +/- 7.7 g vs. 11.6 +/- 4.9 g) and length (delta 1.8 +/- 0.3 cm vs. 1.12 +/- 0.44 cm) in ad libitum fed uremic rats. This was accompanied by increased food utilization ratio (0.146 vs. 0.065 g weight gain per g food intake). A similar increment of growth and food utilization ratio was also observed in GH versus solvent infused controls, either pairfed as for the uremic animals or fed ad libitum. Despite administration of GH, growth was not completely restored to normal in uremic animals. Circulating immunoreactive IGF I was not significantly increased by GH infusion in either uremic animals or controls. Histological analyses of the proximal tibia showed increased rate of longitudinal growth, as evaluated by tetracyclin-labeling, and increased volumetric density of primary spongiosa with unchanged width of primary spongiosa trabecules when GH was infused in uremic animals. The data suggest that growth impairment in the uremic rat is partially responsive to GH, and this is not accompanied by an increase of circulating IGF I. Therapeutic trials with recombinant GH in uremic children appear justified. PMID- 3352161 TI - Renal functional changes in experimental cystic disease are tubular in origin. AB - Chronic (30 weeks) structural and functional changes were correlated in diphenylthiazole (DPT)-induced polycystic kidney disease (PKD) in rats. DPT induced two different types of progressive tubular changes: cystic transformation and hyperplastic/atrophic tubular changes. Cystic changes diffusely involved collecting tubules in the outer medulla and cortex, and they were progressive over 30 weeks. Hyperplastic/atrophic changes occurred as clusters of tubules in the cortex and involved between 25% and 50% of tubular profiles after 12 and 30 weeks of drug treatment. Thus, the two types of tubular change were independent of each other and represent different cellular responses to the drug. DPT treatment induced no detectable light- and electron-microscopic or histochemical alterations in glomeruli or renal blood vessels. Renal functional changes consisted of: (1) early (4 weeks) and persistent impairment of concentrating ability; (2) a progressive drop in creatinine clearance and elevation in BUN; and (3) the late onset (30 weeks) of moderate proteinuria. These findings suggest that cystic as well as hyperplastic-atrophic tubular changes contribute to the loss of tubular and renal function in DPT-induced PKD. Both types of tubular lesions may have a role in the development of impaired renal function in other forms of experimental and clinical PKD. PMID- 3352162 TI - A focus of tissue necrosis increases renal susceptibility to gentamicin administration. AB - The purpose of this study was to determine whether a retained focus of necrotic tissue predisposes to aminoglycoside-induced acute renal failure (ARF). Rats were subjected to either (1) 25% liver ligation, creating a focus of ischemic tissue which was left in place; (2) 25% liver resection; or (3) sham liver ligation. Gentamicin, 80 mg/kg bid, was administered for two days after surgery to all three groups. A fourth group was subjected to 25% liver ligation but no gentamicin therapy. Only rats subjected to partial liver ligation plus gentamicin treatment developed ARF, manifested by azotemia (BUN 80 +/- 2; creatinine 1.63 +/ 0.21; mg/dl) and tubular necrosis. This occurred in the absence of any discernible reduction in arterial blood pressure, renal blood flow, excessive weight loss, or ascites formation. The partial liver ligation-gentamicin group had 70% higher renal gentamicin concentrations than the liver resection gentamicin controls (P = 0.01). To assess whether factors released from necrotic liver might account for these findings, additional rats were infused with: (1) 1 ml of a soluble liver extract alone; (2) 1 ml of liver extract plus gentamicin; or (3) 1 ml of saline plus gentamicin. Only the liver extract/gentamicin group developed ARF (BUN 88 +/- 13; creatinine 1.46 +/- 0.25). This occurred in association with a 110% increase in renal gentamicin uptake (P less than 0.03). In separate experiments, 5 ml liver extract infusions caused ARF (BUN 118 +/- 7; creatinine 2.1 +/- 0.18) without gentamicin treatment. In conclusion, a focus of liver necrosis can predispose to experimental gentamicin nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352163 TI - Lack of glomerular hemodynamic stimulation after infusion of branched-chain amino acids. AB - Renal hemodynamics (Inutest. CPAH) were studied in five adult volunteers infused on separate occasions with branched-chain amino acids (BCAA), a mixture of nonessential and essential amino acids of the same volume, osmolality and nitrogen content, and 0.9% saline solution. BCAA infusion caused moderate renal vasoconstriction, a slight increase of GFR and a progressive rise of the filtration fraction (FF), whereas the amino acids mixture induced a significantly higher increase of GFR and a state of renal vasodilatation without altering the FF. The volume expansion with 0.9% saline did not cause any notable hemodynamic modification except for reduced FF. This study demonstrates that whereas a state of hyperfiltration and hyperemia is specifically induced by an amino acid mixture independently of volume expansion and osmolar load, the administration of BCAA provides nitrogen without renal hemodynamic stimulation. PMID- 3352164 TI - [Emergency and urgent cholecystectomies]. PMID- 3352165 TI - [Surgical treatment of acute calculous cholecystitis]. PMID- 3352166 TI - [Emergency cholecystectomy in acute cholecystitis]. PMID- 3352167 TI - [Biliodigestive anastomoses and papillary sphincterotomies in treating obstruction of the external biliary tract]. PMID- 3352168 TI - [Changes in the liver in recurrent pains following cholecystectomy]. PMID- 3352170 TI - [Diagnosis and treatment of organic hemodynamic disorders in acute pancreatitis]. PMID- 3352169 TI - [Diagnosis and surgical procedure in traumatic lesions of the organs of the hepatopancreaticoduodenal area]. PMID- 3352171 TI - [Primary abscesses of the pancreas]. PMID- 3352172 TI - [Scintigraphy of patients operated on for hepatic echinococcosis]. PMID- 3352174 TI - [Morphofunctional state of the spleen and clinical results of embolization of the splenic artery in liver cirrhosis patients with portal hypertension]. PMID- 3352173 TI - [Transcutaneous transhepatic cholangiostomy in mechanical jaundice]. PMID- 3352175 TI - [Choledochotomy in treating acute and chronic cholecystitis]. PMID- 3352176 TI - [Use of the high-energy CO2 laser in pancreatic resection]. PMID- 3352177 TI - [Transverse rupture of the pancreas]. PMID- 3352178 TI - [Right hemihepatectomy for lymphangioma]. PMID- 3352179 TI - [Rupture of the gallbladder with massive intra-abdominal hemorrhage]. PMID- 3352180 TI - [Retinal detachment following implantation of a posterior chamber lens]. AB - In a series of 6000 cases of pseudophakia following extracapsular cataract extraction and implantation of Simcoe-type posterior chamber lenses, observed for a minimum of 20 months, the incidence of retinal detachment was 21 cases (0.33%). Significant risk factors include male sex (18/21, 82%), high myopia (axial length, over 25 mm in men), intraoperative rupture and late discussion of the posterior capsule. The frequency of retinal detachment following intracapsular cataract extraction without lens implantation was four times greater than that after extracapsular cataract extraction with implantation of a posterior chamber lens. After intracapsular cataract extraction and implantation of an iris fixation lens it was eight times greater. Horseshoe tears, most of which were located in the peripheral superior quadrants, were seen in 14 eyes (76%). In three eyes no holes were detected. Reattachment was less successful in eyes with posterior chamber implants than in phakic eyes with retinal detachments. PMID- 3352181 TI - [Strabismus operations in adolescents and adults]. AB - The present paper reports on 370 strabismic patients who underwent surgery after they had reached visual adulthood (ages 9-81). Surgery was performed for 183 exodeviations (50%), 139 esodeviations (37%) and 48 hypertropias. Patients desiring cosmetic improvement formed the largest group (172 cases, 46.5%). Most of these patients had been suffering from neglected concomitant heterotropias since childhood, but 17% attained subnormal binocular vision. To assess the risk of diplopia preoperatively, the deviation was fully corrected with prisms. Although intolerable persistent postoperative diplopia is a very rare event, the risk of this complication must be clearly pointed out to all visually adult patients. Apparently most adults, even those who have an anomalous retinal correspondence, respond as necessary to the new position of the eye and learn to ignore, suppress or fuse an initial postoperative diplopia. The best surgical results, in terms of restoration of binocular vision, were obtained in cases of intermittent exotropia and manifest exotropia without amblyopia. PMID- 3352183 TI - [Neodymium YAG laser effects on the cornea]. AB - With the Nd:YAG laser it is possible to produce epithelial defects, fractures of Bowman's membrane or ulcer-like defects of the anterior stroma, depending on the distance, intensity, and number of optical breakdowns in front of the cornea. The histologic picture is similar to the well-known changes on the posterior surface of the cornea. The possibility of therapeutic application of the Nd:YAG laser in corneal disease is discussed. PMID- 3352182 TI - [Endothelialization of central isolated leukomata adhaerentes]. AB - Among 820 eyes enucleated between 1980 and 1984 and examined histologically there were 132 globes with central corneal-perforations. In ten of these there was a leukoma adherens not in contact with the anterior chamber angle. In all cases it was endothelialized with formation of a new basal lamina. The mean interval between trauma and enucleation of these ten eyes was 22.6 +/- 16.7 years (0.5-52 years), the mean age of the patients at the time of enucleation 50.7 +/- 22.4 years (15-78 years). Common to all these eyes and therefore of possible pathogenetic importance were: suitable tissue in contact with the corneal endothelium; traumatization of the endothelium and other intraocular structures; intraocular inflammation. The tissue which was pathologically changed and adherent to the cornea served as a "scaffold" for the endothelialization. Healing of the wound caused cell migration and proliferation and, together with intraocular inflammation, secretion of growth factors. PMID- 3352185 TI - [Unilateral infiltration of the optic papilla in chronic lymphatic leukemia]. AB - This paper reports the clinical history of a 72-year-old woman in whom unilateral papilledema was the only organic manifestation of chronic lymphatic leukemia. In the light of the laboratory parameters direct leukemic infiltration of the optic disk was diagnosed by fundus examination and fluorescein angiography. Combined cytostatic therapy bed to a considerable improvement in the patient's clinical condition. PMID- 3352184 TI - [Pediatric neuroblastoma with early bilateral blindness]. AB - The authors present the case history of a child with neuroblastoma and early infiltration of the orbit accompanied by bilateral blindness. The typical clinical signs developed later. The thickening of the periosteum infiltrated by the tumor in the lateral wall of the orbit was demonstrated by computerized tomography. This may be regarded as an early sign of infiltration of the orbit by the neuroblastoma. In the case reported here a severe inflammatory reaction developed in the left orbit and anterior segment during massive chemotherapy and melted the cornea. PMID- 3352186 TI - [Unilateral progressive diabetic retinopathy following a filtering glaucoma operation]. AB - The authors report on three patients with glaucoma and diabetes mellitus, each of whom underwent a unilateral filtering procedure. In all cases a progressive diabetic retinopathy was observed in the treated eye within one to three years. The relative hypotension is considered as a possible cause of the progressive retinopathy. PMID- 3352187 TI - [SI units in the medical field]. AB - A number of SI units important in medicine are listed; special attention is focused on two units which are indispensable in ophthalmology, the kilopascal and the millinewton, as conversions of the old units of pressure and force. Conversion tables are included. PMID- 3352188 TI - [Diurnal fluctuations in human refraction]. AB - The spectacle values of young healthy students were determined morning and afternoon by means of phoropter and autorefractometer. In addition, keratometry was performed. When the morning and afternoon refraction values were compared the latter were found to be about 0.25 diopters lower. This effect cannot be attributed exclusively to changes in the radius of the cornea. PMID- 3352189 TI - [Clinical use of the Canon R10 autorefractometer for determining refraction in children with strabismus]. AB - Using a Canon R 10 Autofractor, refraction was measured in 131 children with squint. Measurements before and after cycloplegia were compared to a reference measurement (taken with the Rodenstock PR 50 hand-held refractometer after cycloplegia). In 80% of the cases the power and axis of the cylinder equalled the reference measurements. Due to accommodation, 40% of the values for spherical equivalents before cycloplegia were false. After cycloplegia 80% of the spherical equivalents were also in agreement with the reference measurement. The short examination time and the interesting fixation target facilitate multiple measurements in children. As a result, refraction can be measured more reliably with the R 10 Autorefractor than with the hand-held refractometer in children from age 2 1/2 or 3. Retinoscopy is only indispensable in cases where it is difficult or impossible to use an autorefractor, i.e., on children aged under 2 1/2 and those with extreme head tilt. PMID- 3352190 TI - [Determining the true size of an object on the fundus of the living eye]. AB - In a preceding paper with the same title the result was represented by curves which enable factors used in calculating the true diameter to be determined. Instead of the curves a quadratic equation is used to produce the same factors. The data for the equation are given in two tables. PMID- 3352191 TI - [Measuring stereoscopic vision using a stereo distance vision instrument and a new stereo near vision instrument]. AB - Normal stereoscopic vision is necessary for many occupations. Therefore, stereoacuity must be measured accurately. Borderline values are not yet available for existing stereo-tests or, as for haploscopic tests, their degree of difficulty is too low. In order to provide an accurate, natural measuring method for both scientific and practical applications, an existing three-rod tester was modified to convert it into a distant-vision stereo-tester, and a new near-vision stereo-tester was designed. A standardized test method was developed and borderline values were established for both units. PMID- 3352192 TI - [Demonstration of thrombocyte membrane proteins with monoclonal antibodies by a flow cytometry bioassay]. AB - Formation of a hemostatic plug is triggered by platelets. Platelet function (e.g. adhesion, aggregation) depends essentially on membrane bound receptor proteins. Conventional chromatographic analysis of these glycoprotein macromolecules is difficult and not appropriate for diagnostic routine. In combination of cytoflowmetric single cell analysis with monoclonal staining we developed a bio assay for qualitative and semi-quantitative analysis of glycoprotein IB and IIB/IIIA on vital fixed platelets. The expression of these molecules was evaluated in 20 healthy volunteers. The assay offers for the first time the possibility of screening the expression of receptor proteins on platelet membranes, which are related to indicate either a functional lack in bleeding disorders or a prethrombotic state due to an enhanced functional potential in high risk patients. PMID- 3352193 TI - Plasma-triglycerides and exercise: a delicate balance. AB - Alimentary lipemia was studied in 12 healthy young men with and without exercise. Three sets of experiments were performed. While continuous exercise of 90 min duration significantly reduced postprandial triglycerides by 26% (study I), this effect could not be observed when exercise was interrupted for 5 min after each 25 min (study II). Plasma free fatty acid concentrations, in the latter experiment, were significantly higher (by 311%) than during rest. When, in a third experiment continuous exercise was compared with intermittent physical activity, the latter condition significantly increased postprandial triglyceridemia, most probably due to precipitous rises of free fatty acids on each interruption of ergometry. It is concluded that in the third experiment the balance between triglyceride removal and triglyceride synthesis was shifted toward the latter. Whether exercise lowers, leaves unaltered, or raises plasma triglyceride levels may depend on subtle changes of experimental design. PMID- 3352194 TI - Urinary factors of kidney stone formation in patients with Crohn's disease. AB - An increased frequency of kidney stone formation is reported in patients with inflammatory bowel disease. In order to investigate its pathogenesis, the concentrations of factors known to enhance calcium oxalate stone formation (oxalate, calcium, uric acid) as well as of inhibitory factors for nephrolithiasis (magnesium, citrate) were determined in the urine of 86 patients with Crohn's disease and compared with those of 53 metabolically healthy controls. Six patients with Crohn's disease already had experienced calcium oxalate nephrolithiasis. Patients with Crohn's disease had significantly higher urinary oxalate and lower magnesium and citrate concentrations. Among all patients magnesium and citrate were significantly lower in those with a positive history of kidney stones. Our results demonstrate that the increased propensity for renal stone formation in patients with Crohn's disease is a result not only of increased urinary oxalate, but also of decreased urinary magnesium and citrate concentrations. PMID- 3352196 TI - [Plaques in the brain]. PMID- 3352195 TI - [Changes in creatine kinase activity in serum following intramuscular injection]. AB - The effect of intramuscular injections of two multivitamin preparations, two excipient preparations without vitamins, and a placebo preparation (glycine 2.5%) on serum creatine kinase activity (S-CK) in ten healthy volunteers (three female, seven male) aged between 23 and 25 years was investigated. One of the multivitamin preparations contained no lidocaine, the other 1% lidocaine. The one excipient formulation was isoosmotic, while the other contained added saline to bring it to the same degree of hyperosomolarity as the multivitamin formulation without lidocaine. The formulations were administered by deep ventrogluteal injection by means of a standardized injection technique. Blood samples were taken before and 6, 12, 24 and 48 h after injection. Following the administration of all the formulations except that of the glycine 2.5%, a marked increase in S CK activity (1260 I.U./l) was observed 12 h after injection (normal range: male: 47-243 I.U./l, female: 39-226 I.U./l). The relative standard deviation for the 12 h S-CK value was 66.4-97.3%. On applying a threeway analysis of variance to the parameter S-CKmax, no significant differences (alpha = 5%) were found between the effects of the multivitamin and excipient formulations. There was a difference between these and glycine 2.5%, however. There were significant differences between individual volunteers but no significant differences based on the sequence in which the injections were given. With regard to the parameter S-CK AUC (area under the curve, trapezoidal rule), a significant difference (alpha = 5%) was observed only between glycine 2.5% and the multivitamin formulation containing 1% lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352197 TI - [Bridges instead of walls]. PMID- 3352198 TI - [The power of speech]. PMID- 3352199 TI - [Is the quality of basic education still ensured despite personnel shortage? Endangered basic education?]. PMID- 3352200 TI - [Transitional program for certified nurses of the Swiss Red Cross. From nursing assistant to nurse]. PMID- 3352202 TI - [Experts too need training]. PMID- 3352201 TI - [No fear of exams]. PMID- 3352203 TI - [Education in general nursing and the demands of care in the population. Necessary changes]. PMID- 3352204 TI - [Considerations with respect to the article "A usable potential". Tensions but also similitudes]. PMID- 3352205 TI - [Nurses facing AIDS: "I experienced the battle between life and death]. PMID- 3352206 TI - [Nursing care in case of catastrophe. Choosing a preventive approach]. PMID- 3352207 TI - [A field to be developed--patient education]. PMID- 3352208 TI - [With regard to the article "Nursing care and military service: deontologic incompatibility?" Taking a personal stand]. PMID- 3352209 TI - [How to start ... to promote health for all by 2000?]. PMID- 3352210 TI - [Potentials and risks of lighting technic in the operating room]. PMID- 3352212 TI - [Living with AIDS]. PMID- 3352211 TI - [Switzerland: educational guidelines]. PMID- 3352213 TI - [Gentamycin]. PMID- 3352214 TI - [Music therapy--a common path]. PMID- 3352215 TI - [What does the nurse have to know about the medical instrument law]. PMID- 3352216 TI - [How important are autopsies today?]. PMID- 3352218 TI - Megaoesophagus in ICRC mice. AB - The occurrence of megaoesophagus in ICRC/HiCri mice afforded opportunities to study the genetics and histology of this condition. The anomaly was found to be inherited as a recessive character. Histology indicated abnormality in the myenteric plexus. PMID- 3352217 TI - A simple method for prevention of coprophagy in the mouse. AB - A series of studies of coprophagy in mice has been conducted from the viewpoints of behaviour and nutrition. Since it was necessary to prevent coprophagy to investigate its significance, an attempt was made to devise a restrainer. A polyethylene bottle was cut and fixed to the mouse so as to prevent its head from reaching its anus when faeces were excreted. The animals were also housed in cages with floors of larger mesh size in order to let the faeces fall through. PMID- 3352219 TI - Altered clinical and histological features of male MM mouse pyelonephritis associated with a change in its microbiology. AB - Radical changes in the clinical, microbiological and histological features of spontaneous pyelonephritis in MM male mice occurred when they were transferred to a new environment after Caesarean derivation. Although the incidence of pyelonephritis remained the same, the survival age was increased. The renal histology indicated a shift to a more chronic form of pyelonephritis with renal amyloidosis as a common feature. At autopsy much more renal scarring was seen, resulting in the 'shrunken' kidney typical of chronic pyelonephritis. Renal lymphocytic accumulations were commonly found in MM mice, but they were also seen frequently in C57BL mice and in germfree stocks of both strains: no association was found between these lesions and pyelonephritis. PMID- 3352220 TI - Effects of repeated blood samplings on locomotor activity, evasion and wheel running activity in mice. AB - The effects of serial blood sampling on nocturnal locomotor activity, evasion, wheel-running activity and body mass were studied in male NMRI mice aged 7-8 weeks. The erythrocyte count, haematocrit and haemoglobin concentration at the beginning and end of the study showed no difference in group 1 (two samples per week, 0.08 ml each) while there was a significant decrease in the group 2 values (three samples per week, 0.08 ml each). The total amount of nocturnal locomotor activity decreased in the animals bled repeatedly while the periods with locomotor activity increased. These alterations appeared particularly after bleeding. In the test-group animals evasion showed a decrease compared with the untreated control animals, but there was no evidence of a relation to the timing of the bleedings. PMID- 3352221 TI - Allelic profile at 37 biochemical loci of two inbred strains of the house mouse derived from wild Mus musculus musculus. AB - Two newly established inbred strains derived from Mus musculus musculus, designated PWD/Ph (F29) and PWK/Ph (F33), were examined for their alleles at 37 biochemical loci located on 12 different chromosomes. The allelic pattern showed characteristic differences from those observed in common inbred strains. The genetic distance D between PWK/Ph and PWD/Ph was 0.027, whereas the corresponding values for the genetic distances between PWK/Ph and C57BL/6J, DBA/2J, BALB/cJ and SWR/J were 0.777, 0.721, 0.721 and 0.838 respectively. New allozymes are described as being controlled by the loci Es-23, Pre-2 and Tam-1. The genetic relationship to M.m.molossinus is indicated by identical alleles at six other loci (Es-2, Es-9, Es-10, Es-11, Es-18 and Es-22). PMID- 3352222 TI - Morphology of the terminal bronchiolar region of common laboratory mammals. AB - The histomorphology of the terminal bronchiolar region of the mouse, rat, hamster, guinea pig, gerbil and rabbit was studied. Although some general structural similarities existed in the progressive intrapulmonary branching pattern of the airway tree between species, there were conflicting accounts in the literature about the presence of the respiratory bronchioles in common laboratory mammals. In our light microscopy study we failed to detect the existence of typical respiratory bronchioles with characteristic interruptions on their walls projecting into the alveoli. Frequently in these species the terminal bronchioles were short and abrupt, opening directly into several alveolar ductules. PMID- 3352223 TI - Infantile disease with microvesicular fatty infiltration of viscera spontaneously occurring in the C3H-H-2(0) strain of mouse with similarities to Reye's syndrome. AB - The clinical, biochemical and histopathological findings of an infantile disease occurring in the C3H-H-2 degree strain of mice, which has similarities with Reye's syndrome in children, is described. PMID- 3352224 TI - Dermal cryptococcosis in a guinea pig. AB - A case of cryptococcosis in a guinea pig with lesions confined to the dorsum of the nose is described. Results of clinical, postmortem and histological examination are discussed. The diagnostic and therapeutic possibilities and problems of cryptococcosis are mentioned. PMID- 3352225 TI - Parent nutrition education: a conceptual model. AB - Getting nutrition information to parents is beneficial for several reasons. Children need support from their parents to implement behavior changes learned in primary prevention interventions. In addition, positive eating behavior changes last longer if interventions are aimed at family attitudes and habits rather than individuals. Finally, parents also can benefit from the information. This article summarizes selected research about the impact of youth-directed nutrition education interventions on parents. A conceptual model is proposed to guide development and evaluation of future interventions with a parent component. PMID- 3352226 TI - Simple procedures for comprehensive vision screening. AB - Visual problems can cause poor academic performance or inappropriate behavior. This article explains simple, easily administered procedures to determine if students have problems with acuity, accommodation, binocularity, or eye movements. The evaluator can use vision screening in conjunction with associated learning or behavior problems to initiate referral to the family vision care specialist. PMID- 3352227 TI - A pilot study on cholesterol screening in the school environment. AB - A newly-developed analyzer measures total cholesterol from a single drop of blood and gives results within minutes. This procedure has made mass cholesterol screening inexpensive and less invasive than methods requiring a venipuncture blood sample, and it offers the opportunity for on-the-spot counseling and referral. In a pilot study, 610 high school students in the Victoria (Tex.) School District were screened for elevated cholesterol. Eighteen percent were found to have cholesterol levels above 180 mg/dl. Mean cholesterol values were higher for females than males, and higher for blacks and Hispanics than whites. Follow-up questionnaires indicated students and their parents understood the basic relationship between cholesterol and cardiovascular disease and how to modify their diet to reduce cholesterol intake. Telephone contact with parents of students with elevated cholesterol showed only about 27% of students with elevated cholesterol had visited a physician subsequent to the cholesterol testing. PMID- 3352228 TI - Differences in black and white adolescents' perceptions about cancer. AB - This study determined if black and white adolescents differed significantly in cancer knowledge, attitudes, and beliefs. Using the Health Belief Model, a 97 item questionnaire was developed by the researchers and completed by 573 black and 297 white junior and senior high school students from a large, midwest school district. Chi-square analyses yielded nine significant differences (p less than .01) between blacks and whites on cancer knowledge (etiology, warning signs, and prevention techniques). Further significant differences were found when items comprising the separate Health Belief Model subscales were analyzed. Blacks and whites differed significantly on cues to action (one item), perceived susceptibility (two items), perceived severity (one item), perceived barriers (two items), perceived benefits (three items), and interpersonal relationships (three items). Blacks and whites received cancer information from the same sources, with the exception of books, which was reported more by blacks. PMID- 3352229 TI - Writing activities that teach about commitment. PMID- 3352230 TI - The nurse's role in identifying children with communication disorders. PMID- 3352231 TI - Pediculosis capitis among primary schoolchildren in urban and rural areas of Kwara State, Nigeria. AB - The prevalence of head lice (pediculosis humanus capitis) was investigated among urban and rural schoolchildren in Ilorin, capital of Kwara State, Nigeria, and two neighboring rural communities. Among the pupils, 57 (3.1%) of 1,842 urban schoolchildren examined were infested, compared with only one (0.1%) of 1.056 rural school pupils. More female pupils had infestations. Children less than age five, primary I pupils, and pupils in primary VI were not infested. Urban schoolchildren with 41-45 lice per head constituted 7.7% of those infested with nits and lice. Most infected children had one-five and 11-15 lice per head. The school health component of the national primary health care scheme should be intensified to screen schoolchildren regularly for pediculosis and other childhood diseases. PMID- 3352232 TI - The checkerboard cardiovascular curriculum: a culturally oriented program. AB - A cardiovascular health education curriculum was designed and pilot-tested with 218 fifth grade students from rural New Mexico. The program incorporated materials, examples, and exercises relevant to the Navajo and Pueblo American Indian and Hispanic cultures of the students. Significant increases in knowledge about the cardiovascular system, exercise, nutrition and obesity, tobacco use, and habit change were found, suggesting a culturally oriented program may help promote a healthy lifestyle in minority group children. PMID- 3352233 TI - Involving nurses in public school sex education. PMID- 3352234 TI - Comparing two methods of preschool and kindergarten hearing screening. AB - Preschool and kindergarten hearing screening programs rely primarily on pure tone audiometry though its reliability with this population has been questioned. Some experts have suggested speech reception testing may be a better indicator of hearing in young children. This study compared screening results on 576 students tested with both pure tone and Verbal Auditory Screening for Children (VASC), a speech reception-based audiometer, and findings of 43 students who could not respond to pure tone testing but did complete VASC. Data indicate VASC was more effective in identifying possible hearing deficits in young children being tested in a screening environment. PMID- 3352235 TI - Courtship violence. AB - Historically, the courtship relationship is thought to be one of peace and tranquility. However, recent research has demonstrated that many dating relationships include violence as a means to resolve conflicts. While differences have been found in the prevalence of violence between high school and college students, both groups report similar locations, causes, and consequences for the behavior. Peers are cited most often as confidants for students who have experienced the violence. Unfortunately, almost 25% of those who experience violence report it to no one. This paper also describes means school health personnel can use to discuss courtship violence with students. By demonstrating awareness of and sensitivity to the problem, school health personnel may be able to counter use of violence in dating relationships. PMID- 3352236 TI - Determination of LSD in urine by capillary column gas chromatography and electron impact mass spectrometry. AB - A procedure for the determination of LSD (lysergic acid diethylamide) in urine at concentrations as low as 0.5 ng/ml is presented. After addition of deuterium labeled LSD as the internal standard, a rapid n-butyl chloride extraction of LSD from urine at pH 8 is followed by formation of the trimethylsilyl (TMS) derivative by treatment with N,O-bis(trimethylsilyl)trifluoroacetamide. The TMS derivative of LSD is identified and quantified by selected ion monitoring with a fused-silica capillary column and electron impact ionization. The procedure was used to monitor LSD concentrations in urine for eight hours following oral administration of 70.5 micrograms of LSD to two human volunteers. Concentrations of LSD determined by the assay are compared with concentrations determined by two other methods of analysis, a radioimmunoassay and a high-performance liquid chromatographic (HPLC) assay. Data concerning the stability of LSD in urine are also presented. PMID- 3352237 TI - Analysis of thiodiglycol in urine of victims of an alleged attack with mustard gas, Part II. AB - Improvements on a procedure for the determination of thiodiglycol in urine are presented. This procedure is based on the conversion of thiodiglycol to mustard gas with concentrated HCl followed by headspace analysis. With deuterated thiodiglycol as the internal standard, more accurate quantitative analyses are possible. Residual amounts of chlorine in the water used for preparation of standard solutions posed problems, and the reaction between chlorine and thiodiglycol in water has been studied. The possible formation of mustard gas from thiodiglycol and sodium chloride was also investigated. The modified procedure was applied to urine samples of several Iranian patients who were victims of an alleged attack with mustard gas and who were treated in European hospitals in 1986. With the exception of one relatively high value (330 ng/mL), the thiodiglycol concentrations were in the same range (10 to 100 ng/mL) as those found during an investigation in 1984. The urine of 20 male controls contained thiodiglycol amounts not above 20 ng/mL. The combined data obtained in 1984 and 1986 (25 Iranian patients and 25 controls) show statistically significant differences. Approximately 80% of the Iranian patients had levels above the 95% confidence limit calculated from the control group. PMID- 3352238 TI - Systematic analysis of solvents and other volatile substances by gas chromatography. AB - Four column packings for screening volatiles in biological material by gas chromatography are evaluated. Retention data are standardized by the calculation of retention indices, and packing materials are compared by discriminating power and identification power. A combination of 5% Carbowax 20M on Carbopack B and 0.3% Carbowax 20M on Carbopack C appears to be best suited for screening. Hydroxy n-alkanes are used as reference substances for the calculation of retention indices. PMID- 3352239 TI - Serum propoxyphene concentrations in a cohort of opiate addicts on long-term propoxyphene maintenance therapy. Evidence for drug tolerance in humans. AB - Propoxyphene, norpropoxyphene, and cyclic dinorpropoxyphene concentrations in the sera of eight opiate addicts were measured by gas chromatography. The addicts were enrolled in a propoxyphene maintenance program and had received 800-1600 mg of propoxyphene napsylate daily for 13-50 months. Serum propoxyphene and norpropoxyphene ranged from 127 to 1070 ng/mL and 814 to 2638 ng/mL, respectively, and their ratio ranged from 0.1 to 0.4. A roughly linear dose-to serum-concentration relationship was found for serum propoxyphene and norpropoxyphene in the cohort. Cyclic dinorpropoxyphene was detected in three of the subjects' sera. Because tolerance to propoxyphene occurs, knowledge of prior drug exposure is necessary to determine whether an elevated propoxyphene or norpropoxyphene concentration is toxic to patients or decedents with apparent propoxyphene overdose. Serum norpropoxyphene concentration exceeds that of propoxyphene following chronic propoxyphene use. Measurable cyclic dinorpropoxyphene implies chronic propoxyphene use but its absence does not exclude chronic use. PMID- 3352240 TI - Determination of methylxanthine stimulants in urine of racing greyhounds by high performance liquid chromatography. Resolution of a contested drug administration case. AB - Results of urine drug analyses for three racing greyhounds that tested positive for caffeine in this laboratory were contested by the animal trainer, who asserted that positives were achieved from deliberate chocolate feeding by a rival kennel. The metabolism and excretion of methylxanthines was examined by high-performance liquid chromatography of extracts of the urine of racing greyhounds force-fed either caffeine (No Doz) or chocolate (Hersheys chocolate drops). Samples from untreated animals served as controls. Study results showed that test animals fed chocolate could be very easily distinguished from those fed caffeine. While the former animals exhibited a prominent theobromine peak with trace amounts of caffeine and theophylline, the caffeine-treated animals gave a prominent caffeine peak with moderate theophylline levels and almost nondetectable theobromine amounts. When these results were compared with the results from the positive authentic racing animals, chocolate feeding was clearly ruled out as an alternative to caffeine administration. PMID- 3352241 TI - Paraquat extraction from plasma or serum without sample deproteinization. AB - Available methods for the determination of paraquat in plasma or serum require sophisticated laboratory equipment and give low recoveries and nonquantitative yields. The method reported here utilizes SepPak C18 cartridges to extract paraquat directly from plasma or serum without deproteinization. It gives complete recovery and does not require the construction of a standard curve. PMID- 3352243 TI - Stability of T-2, HT-2, and T-2 tetraol in biological fluids. AB - The stabilities of tritium-labeled T-2, HT-2, and T-2 tetraol were studied in blood and urine at -70 degrees, 4 degrees, and 23 degrees C for 6 months in the presence of EDTA or NaF. Samples were counted with a radiochromatographic scanner and results indicated the stability of T-2 tetraol greater than T-2 greater than HT-2. Toxins were most stable when stored at -70 degrees C, in the presence of NaF, and in urine (pH 6). They were less stable in saline (control, pH 7) and least stable in blood (pH 8). These results suggest that urine and T-2 tetraol are the biological fluid and metabolite of choice for diagnostic purposes. PMID- 3352242 TI - Gas chromatographic analysis of bromophenylmercapturic acids in urine. AB - A gas chromatographic assay specific for the analysis of bromophenylmercapturic acids in urine is described. The mercapturic acids are first hydrolyzed to form bromothiophenols, which are acetylated, extracted into dichloromethane, and analyzed by gas chromatography with a flame ionization detector. Using samples from rats and mice treated with bromobenzene, the authors make a comparison between this specific method and a nonspecific assay for the determination of total thioethers in urines. PMID- 3352245 TI - Cross-reactivity of oleander glycosides. PMID- 3352244 TI - An attempted homicide using d-CON rat poison. AB - Two adult residents became ill after ingesting food and medication allegedly tainted with d-CON. Police later recovered a box of the poison from the household of the residents and immediately arrested their teenage daughters for attempted homicide. Samples of the food and medication were analyzed for Warfarin, the active ingredient of d-CON, using ultraviolet spectrometry, gas chromatography, and gas chromatography/mass spectrometry. Results confirmed the presence of Warfarin in both the food and medication. PMID- 3352246 TI - A GC/MS method for the determination of 4,4'-diaminodiphenylmethane and substituted analogues in urine. AB - A sensitive and specific gas chromatography/mass spectrometry (GC/MS) method has been developed for the analysis of 4,4'-diaminodiphenylmethane (DDM), 3-ethyl DDM (EDDM), and 3,3'-diethyl DDM (DEDDM) in urine. The method has been applied to the analysis of urine samples from workers exposed to a mixture of all three compounds, and the analysis has shown that EDDM and DEDDM are excreted in urine. We have also shown that there are two classes of conjugates present in urine. EDDM and DEDDM are excreted as heat labile conjugates, while DDM and EDDM are excreted, at least in part, as heat stable but alkaline hydrolyzable conjugates. It is proposed that the method described here could be used for biological monitoring of workers exposed to mixtures of DDM, EDDM, and DEDDM. PMID- 3352247 TI - Composite speech spectrum for hearing and gain prescriptions. AB - Average long-term RMS 1/3-octave band speech spectra were generated for 30 male and 30 female talkers. The two spectra were significantly different in both low and high frequency bands but were similar in the mid-frequency region. It was concluded that a single spectrum could validly be used to represent both male and female speech in the frequency region important for hearing aid gain prescriptions: 250 Hz through 6300 Hz. In addition, the male and female spectra were compared with analogous spectra reported by Byrne (1977) and Pearsons, Bennett, and Fidell (1977). For each sex, significant differences were found among the three spectra in a few frequency bands. The best estimate of the average speech spectrum for each sex was obtained from a weighted average of the three sets of data, excluding the significantly different data points. The long term RMS 1/3-octave band speech spectrum for male and female talkers combined was derived for use in hearing aid gain prescriptions. PMID- 3352248 TI - Babble and random-noise masking of speech in high and low context cue conditions. AB - "Perceptual" masking of speech by multitalker speech (babble) has been widely reported but poorly quantified. Furthermore, the validity of the construct of perceptual masking is questionable. This report describes an experiment using a newly standardized test of speech perception in noise (SPIN) with both babble and spectrally matched random-noise maskers. Classical psychophysical ogive curves were used to model speech recognition as a function of signal-to-noise ratio (S/N). The two maskers yielded speech recognition functions of the same steepness but different locations on the S/N axis. The high-context items of SPIN yielded speech recognition curves with steeper slope and different locations on the S/N axis than the low-context items. These data are used to argue that perceptual masking was not documented (under certain assumptions) and that the superior masking of babble may be explained in purely acoustical terms. Speculations are offered about the possible acoustical differences that could be responsible for the differences in masking effect. PMID- 3352249 TI - Similarities between tactual and auditory speech perception. AB - Perception of synthetic speech continua through the sense of touch and audition was compared utilizing a 32-channel spectrally oriented electrocutaneous display and standard auditory psychophysical procedures. Results indicated a close correspondence between tactual and auditory discrimination and identification for a vowel (/a/-/e/) and a consonant (/sta/-/sa/) continuum. These results suggest that at least some aspects of speech perception are amodal. PMID- 3352250 TI - Interobserver reliability and perceptual ratings: more than meets the ear. AB - The purpose of this study was to examine the reliability of ratings of perceptual characteristics for 10 ataxic dysarthric subjects. The influence of the occurrence of "deviant" speech parameters on the calculation of reliability coefficients was also explored. Results indicated that overall interobserver agreement levels for minimally trained judges compared favorably to reliability coefficients reported in previous studies. Furthermore, levels of overall agreement were above levels of agreement expected on the basis of chance alone. In contrast to overall interobserver agreement, much lower levels of interobserver agreement were obtained when "occurrence reliability" coefficients were calculated for deviant dimensions alone. However, occurrence reliability coefficients surpassed the level of agreement expected on the basis of chance alone for all subjects. Based on the results of this investigation, recommendations are made for modifying standard practices for obtaining interobserver reliability for perceptual ratings of speech characteristics. PMID- 3352251 TI - Commentary on J. Harrington's paper "Stuttering, delayed auditory feedback, and linguistic rhythm". PMID- 3352252 TI - Proverb comprehension in context: a developmental study with children and adolescents. AB - Although previous studies have reported that proverb comprehension remains quite literal before adolescence, the results of the present study indicated that fourth graders performed well on a proverb comprehension task involving contextual information and a written multiple choice format. It was also found that performance on the proverb task steadily improved at least through the eighth grade and was significantly correlated to performance on a perceptual analogical reasoning task. The study contributes to the small but growing body of information concerning language development during the preadolescent and adolescent years and may have some important implications for the assessment of youngsters of this age range who have comprehension deficits that are troublesome, yet difficult to document. PMID- 3352253 TI - Onset sequencing of selected lip muscles in stutterers and nonstutterers. AB - The present study examined lip muscle activity during the speech production of stutterers and fluent speakers to provide information about the nature of stuttering blocks. Depressor Anguli Oris (DAO) and Depressor Labii Inferioris (DLI) were recorded, using hooked-wire electromyography (EMG), in 3 stutterers and 3 nonstutterers during productions of the words "peek", "puck", and "pack." EMG records indicated that nonstutterers activated DAO prior to DLI for production of the initial/p/. Stutterers frequently reversed this sequence of onset, particularly when they stuttered. Results are discussed in terms of mistiming versus anticipatory hypertension hypotheses about stuttering. PMID- 3352254 TI - Stuttering, delayed auditory feedback, and linguistic rhythm. AB - The models of stuttering and delayed auditory feedback (DAF) discussed in this paper are derived from a model of the fluent production of speech in which a rhythmic structure prespecifies the intervals between vowels of stressed syllables. The same rhythmic structure enables a prediction to be made concerning when vowels of stressed syllables will be auditorily perceived. In both stuttering and speech produced under DAF conditions, it is suggested that an incorrect prediction is made concerning when the vowel will be perceived relative to its production. The proposed model of stuttering can account for a variety of other phenomena. Finally, a preliminary model of the onset of stuttering in children is proposed. PMID- 3352256 TI - Subgrouping young stutterers: preliminary behavioral observations. AB - The purpose of this investigation was to identify speech and nonspeech behaviors associated with stuttering of young persons and to use these behaviors in attempts to discern and describe subgroups of these individuals. Forty-three young stutterers (10 girls and 33 boys) produced stutterings and associated behaviors during conversations that were video/audio recorded. Fourteen associated speech and nonspeech behaviors and speech disfluency types were identified and quantified for 10 stutterings from each of the 43 subjects. The 14 associated behaviors and speech disfluency types were further reduced to form three related indices: (a) Sound Prolongation Index, (b) Nonspeech Behavior Index, and (c) Behavioral Variety Index. Results indicated that five subgroups of young stutterers could be identified and described on the basis of these youngsters' number and variety of speech and nonspeech behaviors associated with their stuttering. Findings are taken to suggest that these speech and nonspeech behavioral differences reflect differences in young stutterers' reactions and adjustments to their problem. PMID- 3352255 TI - Vocal shadowing in singers and nonsingers. AB - Five nonsingers and five singers vocally matched the pitches of frequency modulated tones. Subject responses to the shadowing task were analyzed in terms of accuracy, and in terms of duration and speed characteristics of pitch changes. In addition, each frequency change was categorized according to hit, overshoot, undershoot, or oscillate patterns. Singers were found to effect pitch changes in significantly less time than the nonsingers. This finding was attributed to more direct patterns (hits) and faster maximum speeds obtained by the singers. Both groups demonstrated a direct relationship between the size of the pitch change and each of the duration and speed parameters examined. Similarly, for both groups, pitch lowering was faster than pitch raising. Faster speeds and more direct paths in effecting pitch changes were viewed as evidence of greater vocal proficiency in singers as compared to nonsingers. Implications of the data for mechanical and physiological aspects of voice frequency control are discussed. PMID- 3352257 TI - Grammaticality judgments and sentence comprehension in agrammatic aphasia. AB - The relationship between sentence comprehension and grammaticality judgment was examined for both neurologically intact and agrammatic aphasic subjects. Aphasic subjects were able to make grammaticality judgments and comprehension judgments, but were less accurate than healthy control subjects. However, the tasks appeared dissociated for the aphasic subjects: Both the effects of semantic cues and the hierarchy of difficulty of sentence types differed across the two tasks. Further, the findings suggest that not all aspects of morpho-syntactic processing may be equally disrupted in aphasia. The results argue against both a central deficit view of agrammatic aphasia, and a view suggesting that syntactic processing is intact whereas semantic or thematic mapping is not. Instead, the results indicate that the respective performance domains of comprehension and grammaticality judgment may draw on different processes and/or operate on different aspects of the language input. PMID- 3352258 TI - Conversational turn-taking violations in mother-child interaction. AB - Conversational turn-taking violations and corresponding repair mechanisms in mother-child interaction were examined. Thirty mother-child dyads, with children ranging in age from 2:10 (years:months) to 6:3, were videotaped in a 10-min free play situation. The interactions were analyzed for several aspects of overlaps (i.e., simultaneous talking), including general characteristics, participant involvement, turn-taking repair mechanisms, topic characteristics, and communicative intent. Of the 246 overlaps identified, the majority were single, nonconsecutive, and internal (Gallagher & Craig, 1982). Mothers interrupted significantly more than did the children. In terms of repair mechanisms, children exhibited a greater frequency of discontinuation of talking when the mothers interrupted than did the mothers for the comparable situation. Both within and following the majority of overlaps, mothers and children maintained the same topic. Utterances consisting of informative statements were interrupted more often than those consisting of requests. In general, mothers did not appear to be as facilitative of their children's turn-taking skills as they are for other pragmatic skills. PMID- 3352259 TI - Auditory brainstem responses to tone bursts in normally hearing subjects. AB - Auditory brainstem responses were recorded from 20 normally hearing subjects using tone-burst stimuli that were gated with cosine-squared functions. Clear responses were observed over a wide range of frequencies and levels. These responses were highly reproducible within individual subjects and were reliably measured by two independent examiners. ABR thresholds were higher than behavioral thresholds for all frequencies, especially for lower frequencies. Intersubject variability also was greater for lower frequencies. Wave-V latencies decreased with increases in both frequency and level for frequencies from 250 to 8000 Hz and for levels from 20 to 100 dB SPL. The standard deviations seldom exceeded 10% of the mean wave-V latency for any combination of level and frequency. These latencies can be viewed as the sum of both a peripheral and a central component. Assuming that the central component is relatively independent of both frequency and level, changes of wave V latency must be related to peripheral factors, such as travel time along the cochlear partition, and to stimulus characteristics, such as rise time. PMID- 3352261 TI - Prehospital defibrillation by emergency medical technicians. Results of a pilot study in Tennessee. PMID- 3352260 TI - The effect of continuous monaural noise on loudness matches to tinnitus. AB - Data from two psychophysical tasks are presented. In the first, 8 subjects with sensorineural hearing loss and tinnitus adjusted the intensity of a continuous monaural noise to mask the tinnitus. In the second, in the presence of continuous monaural noise, the same subjects adjusted the intensity of a pulsed monaural tone to match the loudness of the tinnitus. The tone was either ipsilateral or contralateral to the noise. Although the noise level required to mask the tinnitus increased substantially, as did the level of the ipsilateral matching tone, the change in the level of the contralateral matching tone was minimal. One possible explanation of these findings is related to the functioning of the peripheral auditory system. PMID- 3352262 TI - Major peripheral vein injury. PMID- 3352263 TI - A case of dermatomyositis. PMID- 3352264 TI - Pneumococcal meningitis and sepsis. PMID- 3352265 TI - Hypoxemia and a left upper lobe density. PMID- 3352266 TI - Patient sexual behavior and the risk for AIDS: the vital role of the physician. PMID- 3352267 TI - Primary care equals primary responsibility. PMID- 3352269 TI - Testing chemotherapeutic combinations in the Human Tumor Colony--Forming Assay. AB - A total of 362 tumor specimens were tested in the Human Tumor Colony--Forming Assay for sensitivity to one of eight drug combinations and to each component drug as a single agent. Peak pharmacologically achievable concentrations of drug were used in continuous exposure. In 175 assays greater than 50% inhibition of colony formation, defined as in vitro sensitivity, was observed for at least one drug. The percent inhibition of the most active single agent closely approximated the percent inhibition of the combination. This relationship was maintained for all tumor types and combinations tested. Resistance in vitro to each drug in a combination predicted resistance to the combination. However, our data suggest that the higher activity of combination chemotherapy relative to single agents is due to an increased probability of finding an agent to which the tumor is sensitive, rather than to a synergistic interaction between drugs. PMID- 3352268 TI - Surgery in papillary thyroid carcinoma: a review of 730 patients. AB - Between 1956 and 1978, 1143 patients with thyroid cancer, nearly half of all patients with thyroid carcinomas in Norway in this period, were seen in our hospital. Of 730 papillary cancer patients, 447 were operated with total thyroidectomy (TT), 179 with hemi-thyroidectomy (HT), while 104 patients had minor thyroid resections (RT). Survival and recurrence rates were similar in the TT- and HT-groups. Local recurrences were seen in 15.2% of the patients following total thyroidectomy and in 16.2% following hemi-thyroidectomy; distant metastases were seen in 10.7% and 11.2%, respectively. Beyond the seventh year of follow-up the cumulative survival was similar following total thyroidectomies, hemi thyroidectomies, and thyroid resections. Unless grossly malignant residues were left behind, the impact of the surgical procedure on prognosis in papillary thyroid cancer seems minor. PMID- 3352270 TI - Cytodiagnosis of soft tissue tumors. AB - The only acceptable definitive diagnosis of a soft tissue mass is histologic or cytologic examination. In recent years, fine-needle aspiration cytology is used in more and more centers for diagnosis of soft tissue masses. We studied 196 aspiration cytologies performed on soft tissue lesions. Out of these, in 48 cases a definitive surgical procedure or open biopsy for histology and further evaluation were performed. There were 25 sarcomas and 23 benign tumors. There was one false negative cytologic result in this group; no false positive cytologies were detected. It seems that cytodiagnosis of soft tissue masses performed by an experienced pathologist is the method of choice, permitting a good diagnostic evaluation, with almost none of the traumatic and oncologic disadvantages of the other methods of biopsy. PMID- 3352271 TI - Papillary thyroid cancer in identical twins. AB - The cases of a set of 19-year old monozygotic twins are presented--the first report of thyroid cancer of follicular origin occurring in identical twins. This report includes a brief review of reports of cancer of various sites in twins. Several studies and reports emphasize genetic factors influencing the concurrence of cancer. Other reports downgrade the likelihood of genetic influence in cancer. PMID- 3352272 TI - Establishment and characterization of a human urinary bladder carcinoma cell line (TSGH-8301). AB - A cell line derived from a well-differentiated human transitional cell carcinoma of the urinary bladder, designated TSGH-8301, was established in vitro. The cultured epithelioid cells exhibited monolayer growth and loss of contact inhibition. The tumorigenicity of TSGH-8301 had been shown by growth in soft agar and tumor induction in athymic nude mice. A reverse ratio of lactate dehydrogenase (LHD) isoenzyme in the cell line and nude mouse-grown tumors was seen predominantly with LDH-V. Chromosomal analysis revealed a heterodiploid stem line with a modal number of 50. Sera of urinary bladder cancer patients reacted with membrane antigens of the TSGH-8301 cells, suggesting the existence of tumor associated antigens in the cells. In vitro chemosensitivity tests of these cells may provide data valuable in the selection of proper anticancer drugs for the TSGH-8301 donor patient. PMID- 3352273 TI - Chordoma: natural history and treatment results in 33 cases. AB - Thirty-three chordomas were observed at the Istituto Nazionale Tumori of Milan from 1933 to 1983: 27 sacrococcygeal, 3 spheno-occipital, and 3 vertebral. The male:female ratio was 2.7, and the median age was 63 yr for patients with sacrococcygeal and 35.2 yr for those with nonsacral chordomas. After pathologic reassessment, distinct cytologic patterns were found: physaliphorous, syncytial, and mixed subtypes, with variable degrees of cytologic atypia. However, no evident difference in survival was documented in relation to these cytohistologic features. Four cases had a prior traumatic fracture, and the pathogenetic role of trauma is stressed. Eight cases were operated with adequate surgery and only three recurred, whereas of 11 inadequate operations, 10 developed local relapse. However, follow-up for recent adequate operations is short. Radiation therapy seemed to be effective with adjuvant or palliative aims. No chemotherapeutic regimen achieved any result; one case had a short complete remission after cis dichlorodiammineplatinum + vinblastine + bleomycin (PVB). This analysis confirms the possibility of achieving radicality with high resection of the sacrum for lesions confined below the second sacral vertebra. Nonsacral chordomas were all unresectable. The best treatment for unresectable lesions seems to be palliative surgery plus radiotherapy. PMID- 3352274 TI - Preliminary observations of malignant melanoma therapy using radiolabeled alpha methyltyrosine. AB - A strategy for cancer therapy using astatine-211-labeled alpha-methyltyrosine (211At-AMT) was studied in cultured B16 melanoma cells and compared to the radiotoxicity of iodine-125-labeled iododeoxyuridine (125IUdR), a thymidine analogue. Both 125I and 211At deliver lethal doses of irradiation to melanoma cells when administered as 125IUdR and 211At-AMT. The alpha decay of astatine-211 is more effective however, needing only a fraction of the cellular radioactivity of 125IUdR to effect comparable clonogenic survival. Compared with 125IUdR, 125I AMT is not cytotoxic because the range of the low energy electrons released does not interact with DNA. Uptake of radiolabeled AMT by melanotic cells is enhanced by theophylline. This preliminary evidence suggests that 211At-labeled melanin precursors may be exquisitely cytotoxic to B16 melanoma cells. PMID- 3352275 TI - Diaphragmatic neurilemoma. AB - The fourth case of diaphragmatic neurilemoma reported in the English literature is presented from our institution. Diaphragmatic tumors are usually benign and most are symptomatic. Utilizing CT scanning, these tumors can today be accurately localized. Excision via thoracotomy or celiotomy is easily accomplished and is the only reliable way to establish the identity of these lesions. PMID- 3352276 TI - Serum pseudocholinesterase levels in murine C3H mammary adenocarcinoma. AB - Serum pseudocholinesterase (PSC) levels may be depressed in persons with malignancy. Deficiency of this enzyme can lead to prolonged apnea in patients who receive succinylcholine. An animal model was developed to study this phenomenon in a controlled setting. C3H/HeJ mice inoculated subcutaneously with C3H mammary adenocarcinoma demonstrated lowering of their PSC levels. This decrease was attenuated by chemotherapy with intraperitoneal cyclophosphamide which also prolonged survival. Non-tumor bearing control animals identically treated with cyclophosphamide experienced a transient drop in PSC on the 29th day which reverted to control values by the 36th day. No gradient of PSC could be demonstrated across a tumor's vascular bed. The effect of other chemotherapy agents on PSC is unknown. A possible role for PSC as a non-specific marker for malignancy is worthy of further study. PMID- 3352277 TI - Laparotomic eventration or colonic prolapse after chemotherapy-induced emesis. AB - Four cases of patients suffering from abdominal scar injuries (laparotomic eventration and colonic prolapse through the site of previous colostomy) associated with antineoplastic chemotherapy-induced emesis are presented. The hypothesis of emetic strain as the main cause of eventration of prolapse is discussed. The authors suggest the need of a routine prophylactic antiemetic treatment in patients submitted to abdominal surgery and subsequent antineoplastic chemotherapy in order to avoid these accidents. PMID- 3352278 TI - Functioning metastases of a nonfunctioning paraganglioma. AB - A case of nonfunctioning paraganglioma, initially qualified as benign, is described. Two years following extirpation, functioning bone and lung metastases were manifested by hypertensive crises and increased levels of vanilmandelic acid and catecholamines in urine. The criteria for benign and malignant paragangliomas are discussed with regard to functional transformation of the tumor described in this case. It is concluded that the phenotypic heterogeneity of the primary tumor cells could explain the difference in biological behavior of the primary tumor and its metastases. PMID- 3352279 TI - Pharmacological aspects of selected herbs employed in hispanic folk medicine in the San Luis Valley of Colorado, USA: II. Asclepias asperula (inmortal) and Achillea lanulosa (plumajillo). AB - Interviews with Hispanic families in the San Luis Valley of Colorado revealed that several herbs, including Asclepias asperula (inmortal) and Achillea lanulosa (plumajillo), are popular ingredients in Hispanic folk medicine preparations. A review of the scientific literature indicates that related species of Asclepias asperula and Achillea lanulosa contain pharmacologically active compounds; these data serve as the focal point for continuing ethnopharmacologic investigation at the University of Colorado School of Pharmacy. PMID- 3352280 TI - Anti-inflammatory activity of oleoresin from Brazilian Copaifera. AB - The oleoresin from Brazilian Copaifera species yielded copalic acid and sesquiterpenes and showed marked anti-inflammatory activity using various experimental models in rats. The oleoresin significantly inhibited carrageenin induced pedal edema following oral doses from 0.70 to 2.69 ml/kg, but was somewhat less effective than 50 mg/kg calcium phenylbutazone. Repeated administration of the oleoresin at a dose of 1.26 ml/kg for a 6-day period reduced granuloma formation with a response comparable to that of 20 mg/kg of calcium phenylbutazone. This same dose of oleoresin also reduced the vascular permeability to intracutaneous histamine. The LD50 value of the oleoresin in rats was estimated to be 3.79 (3.21-4.47) ml/kg. PMID- 3352281 TI - Effect of Teucrium polium boiled leaf extract on intestinal motility and blood pressure. PMID- 3352283 TI - Effect of an aqueous extract of Portulaca oleracea leaves on smooth muscle and rat blood pressure. AB - An aqueous extract of Portulaca oleracea leaves and stems produced a dose dependent relaxation of guinea pig fundus, taenia coli and rabbit jejunum and a dose-dependent contraction of the rabbit aorta. On spontaneously-beating rabbit right atria and electrically-paced left atria, the extract produced a dose dependent negative inotropic and chronotropic effects. On rat blood pressure, the extract produced dose-dependent pressor responses. Phentolamine reduced the relaxant effect of the extract on gut smooth muscle and abolished the contractile response on the aorta as well as the pressor response on blood pressure. Guanethidine and tetrodotoxin had no effect on extract-induced relaxant or contractile responses. On rat blood pressure atropine and cyproheptadine had no effect on extract-induced pressor response, whereas propranolol slightly reduced the pressor response. An increase in extracellular calcium reversed the inhibitory effect of the extract on the rabbit atria. The extract may, therefore, act in part on postsynaptic alpha-adrenoceptors and by interference with transmembrane calcium influx. PMID- 3352284 TI - Effect of Trigonella foenum graceum on blood glucose levels in normal and alloxan diabetic mice. AB - The hypoglycemic effects of a decoction and an ethanol extract of Trigenolla foenum graceum seeds on the serum glucose levels of normal and alloxan diabetic mice were studied. A single 0.5 ml oral dose of 40-80% decoctions to normal as well as alloxanized mice was followed by hypoglycemia developed over a 6-h period. Reduction in blood glucose concentration was highly significant, was maximum at 6 h and was dose-dependent. The hypoglycemia caused by the ethanol extract (200-400 mg/kg) in alloxanized mice was also dose-dependent and 200 mg/kg was comparable in effect to 200 mg/kg tolbutamide. PMID- 3352282 TI - Anti-infectious phytotherapies of the tree-savannah of Senegal (West-Africa) II. Antimicrobial activity of 33 species. AB - The screening of the antimicrobial activity of 33 medicinal plants from Senegal is reported. None of these plants showed activity against the gram-negative test bacteria and against Candida albicans. Extracts of Cnestis ferruginea and Voacanga africana showed strong activity against Aspergillus niger. The former plant was also active against dermatophytes. Twenty-five of the plants tested showed activity against gram-positive bacteria. PMID- 3352285 TI - Antifertility profile of the aqueous extract of Moringa oleifera roots. AB - An aqueous extract of Moringa oleifera roots was investigated for its estrogenic, anti-estrogenic, progestational and antiprogestational activities. Oral administration of extract progressively increased the uterine wet weight of bilaterally ovariectomized rats. This estrogenic activity was supported by stimulation of uterine histo-architecture. When the extract was given conjointly with estradiol dipropionate (EDP), there was a successive reduction in the uterine wet weight when compared to the gain with EDP alone and uterine histological structures were also inhibited. In the deciduoma test, the highest dose of 600 mg/kg interfered with the formation of deciduoma in 50% of the rats, showing some antiprogestational activity. Doses up to 600 mg/kg of the extract orally failed to induce a decidual response in the traumatized uterus of ovariectomized rats. The antifertility effect of the extract appears to be due to multiple attributes. PMID- 3352287 TI - Ethnobotanical observations on Paraguayan Myrtaceae. I. AB - A survey of myrtaceous plants used in traditional medicine in rural areas of eastern Paraguay was undertaken to identify the constituents of crude drugs traded by herbalists. The literature on the use of those plants dating back to colonial times in Paraguay has been examined. Some crude drugs were shown to be mixtures of several genera and species. Those findings put into doubt the outcome of some pharmacological research work carried out without botanical documentation. PMID- 3352288 TI - Effect of Cassia alata leaf extract on hyperglycemic rats. AB - The oral effectiveness of Cassia alata leaf extract on streptozotocin-induced hyperglycemia in rats has been studied and the results compared with glybenclamide. While the extract has no effect on glucose levels in normoglycemic animals, it reduced the blood sugar value in streptozotocin-induced hyperglycemic animals. PMID- 3352286 TI - Pharmacologic studies on the active principles of Calliandra portoticensis leaf extracts. AB - The constituents of ethanolic and aqueous extracts of Calliandra portoricensis leaves were identified to be saponins, tannins, flavonoids and glycosides. The intraperitoneal LD50 of the ethanolic and aqueous leaf extracts in mice were 120.2 and 79.4 mg/kg, respectively. Both extracts inhibited the ulcerogenic effects of pylorus ligation and stress (cold-restraint) in rats at a dose of 50 mg/kg i.p. The anti-ulcer effects of the aqueous extract were always more significant than that of the ethanolic extract. This indicates that the higher content of the saponins and/or tannins of the leaf extract may be responsible for the anti-ulcer effects. The leaf extracts also had antimicrobial effects against Escherichia coli, staphylococcus aureus and Staphylococcus faecalis. Preliminary screening using isolated smooth muscle indicated some anticholinergic potential. PMID- 3352289 TI - Valve prostheses in children: a reassessment of anticoagulation. AB - We have previously published evidence that children with St. Jude Medical prostheses on the left side of the heart may not require anticoagulation. Between March 1979 and September 1986, we followed up 48 patients who had no anticoagulant therapy for up to 7 years after valve replacement, an aggregate of 122 patient-years. The 25 male and 23 female patients ranged in age at implantation from 5 months to 21 years (12 +/- 6 years, mean +/- standard deviation). Five patients (all with complex associated malformation) died in the hospital (10%), and nine died late (22%). None of the early and one of the late deaths was associated with a thrombosed prosthesis. During follow-up, seven thrombotic (one mitral, one aortic) or thromboembolic (two mitral, three aortic) events occurred (5.7 +/- 2.1 per 100 patient-years). Of these seven events, five occurred within the last 14 months of the study. There was no relation of these events to age of patient at implantation, age at the time of even, gender, or site of implantation. Concurrently, we have followed up 340 adult patients with St. Jude Medical prostheses who had warfarin sodium (Coumadin) anticoagulation for 875 patient-years. By the end of this study, the children who did not receive anticoagulants were significantly less free of thrombotic and thromboembolic events than the adults who did receive anticoagulants (p less than 0.01). PMID- 3352291 TI - Pericardial heterografts: why do these valves fail? AB - Eighteen explanted pericardial heterografts were studied (16 standard Ionescu Shiley, one Hancock, and one Mitroflow). Regurgitation was the reason given for explantation of all the Ionescu-Shiley valves. The other two valves were removed for technical reasons. All the Ionescu-Shiley valves had commissural tears and there was concomitant gross calcification in 10 of the 16 valves. In addition, an apparent increase in cusp area had caused "leaflet sagging". The explanted leaflets were thicker and stiffer than leaflets from an unimplanted valve. These features were confirmed directly with an animal model of subcutaneous implantation. Examination with an electron microscope revealed that these changes in mechanical properties seemed to be linked to fiber separation and infiltration by an amorphous proteinlike matrix. The durability of the glutaraldehyde-fixed pericardium depended on a number of factors. Early and midterm failure appeared to be stress induced. Predisposition to high mechanical stresses near the stent was exacerbated by the changes induced by the host environment. This problem was aggravated further in the Ionescu-Shiley valves by stress concentrations around the hole associated with the holding suture. In the long term, collagen disruption associated with leaflet flexure was followed by secondary calcification at the boundary between the intact and disrupted material. PMID- 3352290 TI - Ten-year experience with pericardial xenograft valves. AB - Five hundred fifty-three pericardial xenografts were inserted in 520 patients during a 9-year period at the Fu Wai Hospital in Beijing. The bovine pericardial xenograft was modeled after a similar type of prosthesis manufactured by Shiley Inc. (Irvine, Calif.). The late mortality rate in this series was only 1.8% per annum and the actuarial survival rate was 73.0% +/- 12% at 10 years. There was a very acceptable low incidence of thromboembolism of 0.41% per annum without the need for permanent anticoagulation. This is similar to the clinical reports with other tissue valves. The main question is the durability of the tissue prosthesis or, in other words, the freedom from valve-related clinical complications. In this series, the expected actuarial valve durability rate was 75.0% +/- 8.8% at 10 years. Whether this will continue to hold up over the next follow-up period is unclear. Certainly other tissue prostheses have shown significant degeneration rates beginning after the sixth year that have risen progressively thereafter. In any case, given the relatively low probability of thromboembolic phenomenon without anticoagulation, the trade-off of a prosthesis that may not be as durable as the mechanical ones is certainly acceptable. PMID- 3352292 TI - Relationship of right and left ventricular negative diastolic pressures, hypercontractility, and relief of outflow tract obstructions. AB - Continuous postoperative right and left ventricular diastolic pressures were measured in 12 consecutive patients undergoing pulmonic valvotomy and in 13 consecutive patients undergoing membranectomy and myectomy for discrete subaortic stenosis. All 25 patients had positive preoperative diastolic ventricular pressures. Negative ventricular diastolic pressure was detected immediately postoperatively in all 25. The lowest left ventricular negative diastolic pressure was -38 mm Hg, and the lowest right ventricular negative diastolic pressure was -28 mm Hg. Intravenous administration of volume (blood) reduced the right ventricular negative diastolic pressure significantly (from -14.8 +/- 9.2 to -6.4 +/- 6.8 mm Hg, p less than 0.001) and decreased right ventricular rate of pressure rise from 1100 +/- 320 to 380 +/- 180. Left ventricular negative diastolic pressure was not significantly affected (from -17 +/- 11 to -14.7 +/- 11 mm Hg). Left ventricular negative diastolic pressure disappeared spontaneously 6 to 9 hours postoperatively in association with a spontaneous decrease of left ventricular rate of pressure rise (from 3450 +/- 610 to 2100 +/- 660 mm Hg/sec). We conclude that negative right and left ventricular pressures are common findings immediately after surgical relief of outflow obstructions. Hypercontractility is the main reason for these phenomena. Volume load reduces the right ventricular negative diastolic pressure, but has insignificant effect on left ventricular negative diastolic pressure. The pathogenesis of the hypercontractility is discussed. PMID- 3352293 TI - Pulmonary hypertension in isolated aortic stenosis. Hemodynamic correlations and follow-up. AB - The clinical, hemodynamic, and angiographic data on 92 patients with severe isolated aortic stenosis were reviewed to determine the incidence and mechanism of pulmonary hypertension. The status of each of these patients was determined 1 to 8 years after diagnosis by cardiac catheterization. Patients were divided into three groups on the basis of the pulmonary artery systolic pressure: group 1 (less than or equal to 30 mm Hg), 46 patients; Group 2 (31 to 50 mm Hg), 31 patients; and Group 3 (greater than 50 mm Hg), 15 patients. The prevalence of pulmonary hypertension was 50% (46/92) and that of severe pulmonary hypertension, 16% (15/92). There was no significant difference in age, aortic valve gradient, or valve area among the three groups. There was a significant positive correlation in left ventricular end-diastolic pressure (group 1, 15.5 +/- 7.2 mm Hg; group 2, 23.3 +/- 8.1 mm Hg; and group 3, 29.5 +/- 5.8 mm Hg; R = 0.56, p less than 0.01). There was also a significant negative correlation in left ventricular ejection fraction (group 1, 67.5% +/- 14%; group 2, 62.3% +/- 13.8%; and group 3 49.9% +/- 18.3%; R = 0.43, p less than 0.01). Of the 92 patients, 85 had aortic valve replacement with four (4.7%) hospital deaths. Follow-up showed excellent symptomatic relief in all three groups. Thirteen of the 15 patients in group 3, with severe pulmonary hypertension, had aortic valve replacement. There were no hospital deaths and only one noncardiac death at follow-up in Group 3 patients, and 11 of the 12 surviving patients were in New York Heart Association functional class I. We conclude that pulmonary hypertension is common in isolated aortic stenosis and is related to an elevated left ventricular end-diastolic pressure, frequently with preserved systolic function. Surgical results are excellent. PMID- 3352294 TI - Effects of diltiazem cardioplegia on global function, segmental contractility, and the area of necrosis after acute coronary artery occlusion and surgical reperfusion. AB - We investigated the effects of diltiazem cardioplegia on myocardial function and infarct size in the region of the left anterior descending artery after acute occlusion and reperfusion during cardiopulmonary bypass. Sheep (30 kg) were subjected to 1 hour of regional myocardial ischemia by occlusion of the left anterior descending artery and assigned to a control (n = 8) or experimental group (n = 5). Control animals were placed on cardiopulmonary bypass and the heart arrested with potassium cardioplegia. The left anterior descending artery was released and two additional doses of 100 ml of cardioplegic solution were infused during the total cross-clamp time of 30 minutes. The animals were then weaned from bypass after 1 hour and beating, working reperfusion maintained for an additional 4 hours. The experimental group followed the same protocol except that the cardioplegic solution contained diltiazem (1.4 mg/L). Segmental myocardial function was determined by pairs of ultrasonic crystals in the area at risk, control segment, and minor axis. Global contractility was determined from maximum derivative of left ventricular pressure and cardiac output. The area at risk was determined by injecting monastral blue dye into the left atrium with the left anterior descending artery briefly reoccluded, and the area of necrosis was determined by measuring with a planimeter non-triphenyltetrazolium chloride stained areas in the sectioned left ventricle. After 5 hours of reperfusion, not only did the diltiazem group demonstrate better global contractility as defined by the derivative of left ventricular pressure (1853 +/- 292 versus 979 +/- 191, p = 0.05) but, in addition, the systolic shortening in the ischemic area improved significantly when compared with the control group (9.4 +/- 4 versus 2.13 +/- 0.77, p = 0.05). The group receiving diltiazem cardioplegia had an area of necrosis to area at risk ratio of 31.4% +/- 3%, which was significantly better than this ratio in the control group of 60.75% +/- 7% (p = 0.01). Diltiazem cardioplegia results in improved global and segmental contractility and limits the infarct size after occlusion of the left anterior descending artery and surgical reperfusion. PMID- 3352295 TI - The immature and the mature myocardium. Responses to multidose crystalloid cardioplegia. AB - This study was designed to determine whether multidose St. Thomas' Hospital cardioplegic solution is as effective for preservation of the immature myocardium during ischemia as it is for the mature myocardium. An isolated working heart model was used. Sets of six hearts from immature (3 to 4 weeks, 500 gm) and mature (24 weeks, 2 kg) rabbits were subjected to 60, 90, or 120 minutes of ischemia. Myocardial protection consisted of infusion of cardioplegic solution every 30 minutes at 4 degrees C in a dose of 10 ml/kg of animal weight and maintenance of hypothermia at 10 degrees C by immersion in a cold saline bath. The percent recovery of preischemic aortic flow was lower in the immature than the mature hearts after 90 minutes (60.3% +/- 7.4% versus 101.8% +/- 4.3%) and after 120 minutes (57.4% +/- 10.6% versus 91.1% +/- 13.6%) of ischemia (results expressed as mean value +/- standard error of the mean, p less than 0.05). There were no differences between the mature and the immature hearts in the recovery of heart rate, left atrial pressure, mean aortic pressure, or glycogen stores. Adenosine triphosphate levels measured at the end of the experiment were not different from control in the immature hearts subjected to 60 or 90 minutes of ischemia, but did decline after 120 minutes of ischemia (18.5 +/- 0.8, 16.9 +/- 1.3, 16.6 +/- 0.6 versus 12.3 +/- 1.8 mumol/gm dry weight, p less than 0.05). Adenosine triphosphate levels in the mature hearts were lower than control in hearts subjected to 60, 90, and 120 minutes of ischemia (18.0 +/- 1.2 versus 13.6 +/- 1.1, 12.8 +/- 0.9, 13.7 +/- 1.5 mumol/gm dry weight, p less than 0.05). Multidose St. Thomas' Hospital cardioplegia does not provide adequate preservation of hemodynamic function in the immature rabbit heart, even though myocardial high-energy stores are well preserved. Additional work is necessary to clarify the mechanism of this finding and to develop appropriate methods for protection of the immature myocardium. PMID- 3352296 TI - The effect of temperature and hematocrit level of oxygenated cardioplegic solutions on myocardial preservation. AB - The ideal temperature and hematocrit level of blood cardioplegia has not been clearly established. This study was undertaken (a) to determine the optimal temperature of blood cardioplegia and (b) to study the effect of hematocrit levels in blood cardioplegia. A comparison of myocardial preservation was done among seven groups of animals on the basis of variations in hematocrit levels and temperature of oxygenated cardioplegic solution. The experimental protocol consisted of a 2-hour hypothermic cardioplegic arrest followed by 1 hour of normothermic reperfusion. Group 1 received oxygenated crystalloid cardioplegic solution at 10 degrees C. Groups 2 through 7 received oxygenated blood cardioplegic solution with the following hematocrit values and temperatures: (2) 10%, 10 degrees C; (3) 10%, 20 degrees C; (4) 10%, 30 degrees C; (5) 20%, 10 degrees C; (6) 20%, 20 degrees C; and (7) 20%, 30 degrees C. Parameters studied include coronary blood flow, myocardial oxygen extraction, myocardial oxygen consumption, and myocardial high-energy phosphate levels of adenosine triphosphate and creatine phosphate during control (prearrest), arrest, and reperfusion. Myocardial oxygen consumption at 30 degrees C during arrest was significantly higher than at 10 degrees C and 20 degrees C, which indicates continued aerobic metabolic activity at higher temperature. Myocardial oxygen consumption and the levels of adenosine triphosphate and creatine phosphate during reperfusion were similar in all seven groups. Myocardial oxygen extraction (a measure of metabolic function after ischemia) during initial reperfusion was significantly lower in the 30 degrees C blood group than in the 10 degrees C blood group at either hematocrit level and in the oxygenated crystalloid group, which suggests inferior preservation. The hematocrit level of blood cardioplegia did not affect adenosine triphosphate or myocardial oxygen consumption or extraction. It appears from this study that blood cardioplegia at 10 degrees C and oxygenated crystalloid cardioplegia at 10 degrees C are equally effective. Elevating blood cardioplegia temperature to 30 degrees C, however, reduces the ability of the solution to preserve metabolic function regardless of hematocrit level. Therefore, the level of hypothermia is important in blood cardioplegia, whereas hematocrit level has no detectable impact, and cold oxygenated crystalloid cardioplegia is as effective as hypothermic blood cardioplegia. PMID- 3352298 TI - Reversal of reperfusion injury after ischemic arrest with pressure-controlled intermittent coronary sinus occlusion. AB - Recent experimental studies have shown that pressure-controlled intermittent coronary sinus occlusion effectively reduces both infarct size and myocardium at risk after coronary artery occlusion. This study was undertaken to determine whether this modality was equally effective in altering reperfusion damage after a period of ischemic arrest. Fourteen pigs were placed on cardiopulmonary bypass and subjected to 2 hours of ischemic arrest with multidose potassium crystalloid cardioplegia supplemented with topical and systemic hypothermia (28 degrees C). During arrest, the mid-left anterior descending artery was occluded with a snare, which was released immediately after aortic unclamping. In seven pigs, a 7F balloon-tipped catheter was positioned in the coronary sinus and pressure controlled intermittent coronary sinus occlusion was performed for 60 minutes after aortic unclamping. Seven other pigs served as controls. Parameters measured included stroke work index, ejection fraction, and myocardial pH in the distribution of the distal left anterior descending artery. Pigs treated with pressure-controlled intermittent coronary sinus occlusion had a significantly higher myocardial pH (6.99 +/- 0.06 versus 6.67 +/- 0.05, p less than 0.01), ejection fraction (50% +/- 2% versus 33% +/- 6%, p less than 0.01), and stroke work index (0.87 +/- 0.07 versus 0.61 +/- 0.05 gm-m/kg, p less than 0.01) after 60 minutes of reperfusion compared with those of the group not treated in this way. We conclude that pressure-controlled intermittent coronary sinus occlusion effectively reverses reperfusion damage after periods of ischemic arrest. PMID- 3352297 TI - The effect of oxygen free radical scavengers on the recovery of regional myocardial function after acute coronary occlusion and surgical reperfusion. AB - This study investigated the effects of the oxygen free radical scavengers superoxide dismutase and catalase, the peroxide ion inhibitor, in crystalloid potassium cardioplegic solution on infarct size and global and regional myocardial function after occlusion of the left anterior descending artery and surgical reperfusion in young sheep on cardiopulmonary bypass. After 1 hour of occlusion, the animals were randomized to receive either routine potassium cardioplegia or cardioplegia with superoxide dismutase and catalase. Global hemodynamics measured by maximum rate of pressure rise showed significant improvement after 5 hours of reperfusion in the group treated with superoxide dismutase and catalase (1843 +/- 163 versus 979 +/- 191, p less than 0.001). Regional myocardial function was measured by ultrasonic crystals implanted in the ischemic area and in a nonischemic control segment. The percent systolic shortening or bulging was calculated. At end of reperfusion in the animals treated with superoxide dismutase and catalase, there was active shortening in the ischemic area after reperfusion of +9.2% +/- 0.4% versus 2.1% +/- 0.8% in untreated animals (p less than 0.001). Infarct size measured by triphenyltetrazolium chloride staining showed significant difference (p less than 0.001) between animals treated with superoxide dismutase and catalase (0.9% +/- 0.1%) and control animals (61% +/- 70%). Superoxide dismutase and catalase given in the cardioplegic solution before reperfusion of an acutely ischemic area of myocardium enhances recovery of contractile function and results in a significant reduction in infarct size, which suggests improved salvage of the ischemic myocardium. PMID- 3352299 TI - Right atrial isolation: a new surgical treatment for supraventricular tachycardia. I. Surgical technique and electrophysiologic effects. AB - This study describes the surgical technique and electrophysiologic effects of isolating the right atrium while preserving normal function and continuity of the sinoatrial node with the remainder of the heart. Thirteen adult mongrel dogs underwent normothermic cardiopulmonary bypass. A posterorlateral right atriotomy was performed that encircled the upper right atrium but excluded the atrial pacemaker complex. The incision was extended anteromedially to the tricuspid valve anulus just anterior to the membranous interatrial septum and inferiorly just posterior to the os of the coronary sinus and the tricuspid valve anulus. Postoperatively, electrophysiologic data confirmed (1) that the body of the right atrium was electrically isolated from the remainder of the heart, (2) that the sinoatrial node continued to function normally, and (3) that the sinoatrial node remained in continuity with the left atrium and ventricles. Right atrial tachycardia was simulated by rapid right atrial pacing and was confined to the isolated right atrium. Moreover, the simulated tachycardia did not affect normal sinus rhythm or normal atrioventricular conduction. It is concluded that isolation of the right atrium with preservation of normal sinoatrial node function and continuity is feasible. This technique offers an alternative to the current surgical approaches for management of refractory supraventricular tachycardias that arise in the right atrium. PMID- 3352300 TI - Right atrial isolation: a new surgical treatment for supraventricular tachycardia. II. Hemodynamic effects. AB - Surgical isolation of the body of the right atrium presents a unique hemodynamic situation in which the synchronous right atrial contraction (kick) is lost but the synchronous left atrial contraction is preserved. The hemodynamic effects of this procedure were evaluated by pacing at selected atrial sites postoperatively to simulate (1) sinus rhythm with a synchronous right atrial kick, (2) sinus rhythm without a synchronous right atrial kick, (3) right atrial tachycardia propagated to the entire heart (propagated right atrial tachycardia), and (4) right atrial tachycardia confined to the isolated right atrium with sinus rhythm in the rest of the heart (confined right atrial tachycardia). Hemodynamic data recorded under these four conditions showed that (1) during sinus rhythm, synchrony of right atrial contraction had no significant effect on any of the hemodynamic parameters studied and (2) conversion from propagated right atrial tachycardia to confined right atrial tachycardia resulted in an increase in mean arterial pressure (65 +/- 5 to 78 +/- 3 mm Hg, p less than 0.005) and stroke volume index (9 +/- 1 to 19 +/- 3 ml/beat/m2, p less than 0.005) with a decrease in left atrial pressure (9 +/- 2 to 5 +/- 1 mm Hg, p less than 0.05) and right atrial pressure (6 +/- 1 to 5 +/- 1 mm Hg, p less than 0.05). Moreover, cardiac hemodynamic performance remained within normal limits for up to 14 weeks. Thus the right atrial isolation procedure does not adversely affect cardiac hemodynamics despite the loss of synchronous right atrial contraction during sinus rhythm, and the procedure prevents hemodynamic deterioration during right atrial tachycardia. PMID- 3352301 TI - Long-term clinical results after aortic valve replacement with the Bjork-Shiley prosthesis. AB - The results of 1753 consecutive aortic valve replacements performed during a 15 year period (1969 to June 1983) are reported. All patients received one of five models of the Bjork-Shiley valve. The follow-up was 99.6% complete and covered 10,658 patient-years (mean 6.4 years). An autopsy was performed in 72% of all fatalities. Early mortality was 5.5%. The early mortality rate for patients undergoing isolated, elective aortic valve replacement between 1979 and 1983 was 2.3%. Five-, 10-, and 15-year actuarial survival rates (early mortality excluded) were 85%, 70%, and 54%, respectively, and complication-free survival rates at the same time intervals were 78%, 59%, and 42%. Eighteen percent of the late deaths were considered valve related. Anticoagulant-related hemorrhage was the single most common valve-related complication (1.4/100 patient-years) and the most common valve-related cause of death (0.3/100 patient-years). The incidences of embolism and valve thrombosis were closely related to the efficacy of the anticoagulant program. Fourteen of 19 valve thromboses occurred among 180 patients without anticoagulants. The incidences of embolism and valve thrombosis among 1573 patients with continuous anticoagulant treatment were 0.7 and 0.06/100 patient-years, respectively. Six strut fractures occurred, all in convexo-concave valves. There was no mechanical failure among the Monostrut valves. The incidence of "prosthetic failure" (ie, valve-related complications [not leakage] necessitating reoperation or causing the patient's death) was 0.6/100 patient years. The incidence of embolism and prosthetic failure was similar for the different valve models, and these long-term results might therefore be considered representative for all Bjork-Shiley aortic valves. PMID- 3352303 TI - The omentum in the management of complicated cardiothoracic problems. AB - The pedicled omentum finds use in cardiothoracic surgery for management of complicated problems and prevention of serious complications. Its blood supply is excellent and is capable of inducing neovascularity. Based on the right gastroepiploic artery, it reaches anywhere in the thorax or neck. Its bulk helps to fill infected spaces. Thirty-seven patients have been treated with the pedicled omentum. In 16 patients the goal was preventive, to avoid bleeding, anastomotic leakage, or infection or to provide a source of fibroplasia or neovascularity. In eight patients with cervical exenteration the flap protected against innominate artery erosion and esophageal leakage, generally in an irradiated field. In six patients it permitted primary healing of heavily irradiated trachea--formerly unlikely. It was also used to provide coverage of a chest wall prosthesis in two patients. In 21 patients the omentum was used to obtain healing in the presence of infection. Bronchopleural fistulas were successfully closed in eight of nine patients. Six mediastinal infections that developed after cardiac operations were successfully treated. Four unusual vascular infections necessitated the use of omentum. Two patients had closure of esophageal perforations buttressed with omentum. This series demonstrates the efficacy of the omentum in the management of complex cardiac, vascular, esophageal, tracheal, bronchial, pleural, and chest wall problems. PMID- 3352302 TI - Cerebral microembolism during cardiopulmonary bypass. Retinal microvascular studies in vivo with fluorescein angiography. AB - To observe microembolic events in the central nervous system during cardiopulmonary bypass, we subjected 21 patients undergoing elective coronary operations to retinal fluorescein angiograms 5 minutes before cardiopulmonary bypass was discontinued. Patients with diabetes or clinically evident cerebrovascular disease were excluded. Bubble oxygenation and nonpulsatile perfusion were used for bypass. After 31 to 167 minutes of cardiopulmonary bypass, all 21 (100%) patients had retinal microvascular occlusions indicative of microembolism. Control fluorescein angiograms obtained preoperatively and in five patients immediately before bypass but after aortic cannulation showed retinal perfusion. During bypass there was a mean of 3.5 (range 1 to 7) blocked arterioles of less than 50 micron caliber and a mean of 6.3 (range 1 to 10) focal areas of capillary nonperfusion per 30-degree field of retina centered on the macula per patient. Repeat studies 30 minutes after discontinuation of bypass showed partial reperfusion with occlusions in four of the five (80%) patients and a decrease in the mean total microembolic count from 12.6 to 4.8 (38%). In later studies at a median of 8 days postoperatively, only two of 16 (12.5%) patients had persistently occluded retinal vessels. The total microembolic count did not correlate with bypass time (r = 0.14) and was not reduced by arterial line filtration with a Pall 40 micron filter (Ultipore) in a subgroup of 11 patients. Twenty patients completed four standardized psychometric tests. Retinal microvascular occlusions were more numerous in those patients with a psychometric deficit (n = 7) than in those with no deficit (n = 13; p = 0.075). In a dog model of cardiopulmonary bypass, eight of nine (88.9%) had retinal microvascular occlusions after 10 to 90 minutes of bypass. Retinal histologic studies revealed intravascular platelet-fibrin microaggregates 20 to 70 micron in diameter and focal ischemic changes in seven of the nine (77.8%) dogs. Six dogs undergoing sham bypass had normal retinal perfusion and histologic findings. This study demonstrates a very high incidence of microvascular occlusions in the territory of the internal carotid artery during bypass consistent with a microembolic origin. The clinical significance of these findings is uncertain. PMID- 3352304 TI - Management of pediatric esophageal perforation. AB - Esophageal perforation is a serious complication necessitating immediate therapy. In a retrospective study we have evaluated the results in 13 children treated for esophageal perforation. Eleven of 13 perforations could be managed conservatively. In one child with extrapleural effusion, tube drainage was performed. The only death in this series occurred in a child who was brought for treatment after a 60-hour delay. Thoracotomy and multiple abscess drainage eventually proved unsuccessful. On the basis of our experience with children with esophageal perforation or with complications after esophageal atresia repair, we conclude that management of esophageal perforation in children differs substantially from therapy in adults and necessitates restrictive treatment guided by clinical symptoms. PMID- 3352305 TI - Early and late results of aortic root replacement with antibiotic-sterilized aortic homograft. AB - Between November 1972 and November 1986, 108 patients aged 5 to 73 years had complete replacement of the aortic root with an aortic homograft into which the coronary arteries were implanted. The main indications were (1) a tunnel type of aortic obstruction involving a hypoplastic ring, (2) a para-aortic annular abscess, (3) prosthetic valve dysfunction, mainly a previous aortic homograft, and (4) aortic stenosis with a small aortic anulus. Eighty-four patients (78%) had previous aortic valve operations. Concomitant cardiac procedures were done in 34 patients (32%). The 30-day mortality rate was 14% (15 patients). The cumulative follow-up period was 180.3 patient-years. The late mortality rate was 6.1% per patient-year (11 patients). The patients were not given anticoagulants postoperatively, but the entire group has been completely free from thromboembolism. The actuarial 5-year survival rate including operative deaths was 72%. The freedom from valve-related death at 5 years after operation is 86% and freedom from reoperation at 5 years is 96%. The use of homografts for replacement of the aortic valve and root in patients with complex lesions affecting these structures has shown encouraging early and late results, with regard to both survival and valve performance. PMID- 3352307 TI - Early and late results of a protocol for simple transposition leading to an atrial switch (Mustard) repair. AB - Inferences: A treatment protocol for patients with simple transposition, consisting of initial balloon atrial septostomy and leading to a delayed atrial switch repair of the Mustard type, in good circumstances, results in survivorship at 1 month, 1 year, 10 years, and 20 years of 95% (95% confidence limits [CL] 90% to 97%), 90% (95% CL 84% to 94%), 83% (95% CL 74% to 90%), and 80% (95% CL 70% to 88%), respectively. Low birth weight adversely affects survivorship. Hypoxia or heart failure accounts for most deaths within the first month and before the atrial switch (Mustard) repair. Most of the few deaths late postoperatively are sudden and they appear to occur particularly in patients who have junctional rhythm. A progressive increase in the prevalence of junctional rhythm has been a risk of the atrial switch repair, and only 76%, 65%, 59%, 56%, and 53% of patients can be expected to be free of this by 1, 5, 10, 15, and 20 years after repair. Important right ventricular dysfunction late after an atrial switch repair, with its adverse affect on the patients' functional capacity, appears to be present in up to 10% of patients after the atrial switch repair, but may not be an immutable risk of this type of repair. About 90% of patients, essentially all of those who do not have right ventricular dysfunction, can be expected to be in New York Heart Association class I or II late postoperatively. PMID- 3352306 TI - Two decades' experience with aortic valve replacement with pulmonary autograft. AB - Aortic valve replacement with a pulmonary autograft was performed on 241 patients between June 1967 and October 1986 at National Heart Hospital, Guy's Hospital, Middlesex Hospital, Harley Street Clinic, and Italian Hospital in London by one of the authors (D.N.R.). The longest follow-up is 18 years 7 months, and the cumulative total follow-up is 1130 patient-years (pt-yr). The overall 30-day mortality rate is 6.6% (16 patients), with no deaths after 1976, and the late mortality rate is 1.7%/pt-yr (19 patients). The actuarial survival rate is 57.3% +/- 9.6% at 19 years. No anticoagulation has been used and there have been no thromboembolic episodes. The incidence of bacterial endocarditis is 1.2%/pt-yr (14 patients), and its actuarial event-free rate is 74.2% +/- 8.1% at 19 years. Reoperation because of failure of the pulmonary autograft was performed on 36 patients, 27 of whom needed valve replacement. The incidence of pulmonary autograft replacement is 2.5%/pt-yr, and its actuarial event-free rate is 48.5% +/- 13.7% at 19 years. For reconstruction of the right ventricular outflow tract, 186 aortic homografts, 26 pulmonary homografts, 16 autologous fascia lata valved conduits, 7 autologous pericardial conduits with or without a valve, and 6 xenograft valved Dacron conduits were used. Thirty-one patients were reoperated on, mostly because of degeneration of this material. Pulmonary rather than aortic homografts are now favored for reconstruction of the right ventricular outflow tract Because of its satisfactory long-term result without the need for anticoagulation, as well as its safety as an established surgical procedure, this operation can be recommended to a wider range of patients. PMID- 3352308 TI - Ventricular aneurysms and other lesions produced by the struts of bioprosthetic valves implanted in sheep. AB - Damage to the posterolateral wall of the left ventricle was found in eight of approximately 700 sheep undergoing mitral valvular replacement as part of animal model studies of bioprosthetic valves. The damage consisted of left ventricular aneurysms in five animals, subacute rupture of the left ventricle in one, acute left ventricular laceration in one, and endocardial scarring in one. Six of the eight bioprostheses were bovine pericardial valves, including five low-profile valves and one standard valve; of the two porcine bioprostheses, one was intentionally oversized and the other was a low-profile supra-annular valve. In each of these animals the damage appeared to have been caused by contact between the most posterior strut of the bioprosthesis and the left ventricular wall. PMID- 3352309 TI - Successful nonsurgical therapy of mural thrombosis of the left atrium after mitral valve replacement. AB - Mural thrombosis of the left atrium is a complication of mitral valve replacement. In this report we present a case of mural thrombosis of the left atrium after mitral valve replacement treated successfully without surgical intervention. PMID- 3352310 TI - Cor triatriatum dexter with anomalous pulmonary venous drainage and sinus venosus atrial septal defect. AB - The atypical location of a membrane in a case of cor triatriatum dexter prompted successful repair of accompanying anomalies, with in situ use of the membrane. The anatomy is described with a review of the literature. PMID- 3352311 TI - Repair of pulmonary artery branches with broadly based autologous pericardial flaps. PMID- 3352312 TI - Management of discrepancy between radial arterial and aortic pressures after cardiac operation. PMID- 3352313 TI - Traumatic bronchopericardial fistula presenting as cardiac tamponade. PMID- 3352314 TI - Benign lymphocytic angiitis and granulomatosis: experience with three cases. AB - Of three patients with lung-biopsy-proven benign lymphocytic angiitis and granulomatosis, two experienced complete resolution of their disease from therapy with chlorambucil and one underwent spontaneous remission with no drug therapy after lung biopsy and removal of a benign spindle cell thymoma. Clinically, it is difficult to determine whether benign lymphocytic angiitis is a low-grade (prelymphomatous) lymphoma or a vasculitis. Its position in this spectrum of diseases is uncertain. Nonetheless, benign lymphocytic angiitis and granulomatosis corresponding to a low-grade angiocentric immunoproliferative lesion is a clinicopathologically useful concept. PMID- 3352315 TI - Incidence of malignant bone and joint tumors in Olmsted County, Minnesota, 1935 through 1981. AB - During the 47-year period 1935 through 1981, 30 cases of malignant bone and joint tumors (in 20 male and 10 female patients) were identified among Olmsted County, Minnesota, residents. The incidence rates per 100,000 population, age-adjusted to the 1970 US total white population, were 1.0 overall, 1.4 for male subjects, and 0.7 for female subjects. Mortality rates, likewise age-adjusted, were 0.7 overall and 1.1 and 0.3 for male and female subjects, respectively. These rates are similar to those from tumor registries, a finding that suggests that reporting of these tumors is relatively complete. The similarity of the incidence and the mortality rates is consistent with the high case-fatality rate. A comparison of the Olmsted County cases with Mayo Clinic referral cases provides some evidence for referral bias, as the referral patients were significantly younger and had significantly more high-grade tumors. PMID- 3352316 TI - Surreptitious use of salicylates: a cause of chronic recurrent gastroduodenal ulcers. AB - We describe five patients who had chronic recurrent gastroduodenal ulcers and pain, intestinal obstruction, bleeding, or a combination of these symptoms. Four patients required surgical intervention because of a poor response to medical therapy. The ulcers recurred in all patients, despite evidence of achlorhydria in two of them. Although the patients denied the use of salicylates, all of them had therapeutic blood levels of salicylates. A salicylate level should be determined in patients with severe ulcer disease that is resistant to medical therapy or that is recurrent after appropriate surgical therapy when the presence of hypergastrinemia or hyperchlorhydria has been definitely excluded. A low serum level of uric acid can also be a clue to the abuse of salicylates. PMID- 3352317 TI - Percutaneous placement of the Greenfield vena caval filter. AB - During the period from August 1986 to August 1987, 50 patients underwent percutaneous placement of a Greenfield vena caval filter from the right femoral vein, left femoral vein, or right internal jugular vein at our institution. All 50 patients had a contraindication to anticoagulation therapy or had complications of anticoagulation for deep venous thrombosis or pulmonary emboli. The percutaneous placement was accomplished in the angiographic suite with use of local anesthesia and was well tolerated by all patients. Only three complications related to the percutaneous approach occurred during the short-term follow-up (3 months to 1 year). These complications were deep venous thrombosis of the leg in two patients and misplacement of the filter in one patient. The three patients tolerated these complications well. We conclude that placement of Greenfield vena caval filters can be readily accomplished by means of percutaneous entry. Our experience demonstrated minimal associated morbidity and no mortality. PMID- 3352318 TI - Surgical resection of carotid body tumors: long-term survival, recurrence, and metastasis. AB - We retrospectively reviewed a 20-year experience with 59 carotid body tumors in 55 patients examined at our institution in order to determine the long-term results of surgical resection, including the rates of distant metastasis, local recurrence, and long-term survival. Complete surgical excision was possible in 52 of the 55 patients (95%). Perioperative mortality was only 2% (1 of 59 procedures), and no operative deaths occurred during the last 10 years of the study. Survival of patients after resection of a carotid body tumor was equivalent to that for sex- and age-matched control subjects. Only one patient (2%) had development of metastatic disease during long-term follow-up. Three patients (6%) had recurrence of the carotid body tumor after complete excision. All recurrent tumors were observed in patients with multiple paragangliomas or a family history of cervical paragangliomas. Therefore, we advocate early surgical resection of all carotid body tumors in low-risk patients. Such early resection maximizes the possibility of cure and minimizes the risks of neurovascular complications associated with large and neglected tumors. PMID- 3352319 TI - Cardiopulmonary function in long-term survivors of childhood Hodgkin's lymphoma: a pilot study. AB - Twelve patients who had received mantle radiotherapy for Hodgkin's lymphoma during childhood underwent cardiopulmonary testing 7 years or more after the initial diagnosis and treatment. All but one patient had been asymptomatic. Results of echocardiography, pulmonary function tests, or exercise studies were abnormal in 9 of the 12 patients. Long-term follow-up of cardiopulmonary function will be important to determine the ultimate significance of these abnormalities. These potential complications must be considered in planning prospective therapeutic studies in children with Hodgkin's disease. PMID- 3352320 TI - Chest pain in a young woman. AB - Chest pain in a young person is often caused by chest wall tenderness, associated with mitral valve prolapse, or attributed to psychologic factors. Ischemic cardiac pain may be overlooked because of its rare occurrence in this age group. A 35-year-old woman complained of substernal chest pressure precipitated by exertion and relieved by rest. The symptom had been noted for 15 years. Worsening of the symptom during dancing prompted her to seek medical advice. She had no other illnesses, was taking no medications, was a nonsmoker, and had no family history of coronary disease. Physical examination disclosed a grade 1 (on the basis of 1 to 6) systolic ejection murmur, an ejection click, and a grade 2 diastolic murmur. An exercise test produced symptoms at 4 minutes. Coronary arteriography showed the absence of a left coronary ostium and filling of the entire coronary system from the right ostial injection through collateral vessels from the right coronary artery. Surgical repair was recommended. Operative intervention showed a dysplastic bicuspid aortic valve with a membrane that covered the left coronary ostium. Excision of the membrane reestablished antegrade blood flow to the left coronary system. A follow-up exercise test revealed normal findings. Because chest pain in a young person is rarely ischemic in origin, benign or noncardiac causes are usually considered; however, if the history suggests ischemic pain, the possible presence of unusual cardiovascular abnormalities should not be disregarded. PMID- 3352321 TI - Predictive equations for basal caloric requirement derived from the data of Boothby, Berkson, and Dunn. PMID- 3352322 TI - Pulmonary lymphocytic angiitis: a nosologic quandary. PMID- 3352323 TI - Using administrative data to predict important health outcomes. Entry to hospital, nursing home, and death. AB - This paper assesses our ability to use administrative data for developing indicators of health status. Traditionally, measures of health status have been derived from interviews. Here indicators from administrative data and from interviews are compared, i.e., their ability to predict important health outcomes for a large representative sample of elderly residents of Manitoba, Canada. Indicators of health status derived from an administrative data system and from health interviews are shown to provide roughly similar predictions of nursing home entry. Administrative data provide significantly better predictions of death and future hospital entry than do variables from interview data. PMID- 3352324 TI - Changes in resident physicians' collective bargaining outcomes as union strength declines. AB - This paper examines the effect of reductions in union bargaining strength on total compensation and compensation mix for resident physicians. The working conditions examined in this paper include hourly wages, life/health insurance, meals on the job, professional liability insurance, and employee grievance procedures. Data for resident physicians with and without collective bargaining agreements are examined for two distinct time periods. The findings suggest that as bargaining strength declined, resident physician unions were less able to deliver advantages in both total compensation and compensation mix. In addition, these unions were more willing to make concessions on fringe benefits than on wage earnings. PMID- 3352325 TI - Daily symptoms and behavioral responses. Results of a health diary with older adults. AB - Research on the health care behavior of older adults in response to symptoms will benefit from having data collection methods that can monitor health actions as they occur on a daily basis. In the present study, symptom experiences over a 2 week period and the actions taken in response to them were studied with a self kept daily diary. Participants were 142 community-resident older persons, aged 62 94. Diary information about number of daily symptoms and the accompanying pain/discomfort was correlated with health perceptions and psychosocial indices obtained in an interview prior to the diary period. Women tended to take a more active response to symptoms than men, particularly in the area of personal care actions. Preventive health behaviors were not strongly related to symptom-related actions. Satisfaction with one's income was the only predictor of seeking professional assistance. Overall, the diary method is feasible to use with older adults, although certain groups may require special consideration (e.g., the visually impaired, persons with multiple symptoms per day, or those with a limitation on writing ability). PMID- 3352326 TI - Malpractice claims experience associated with fertility-control services among young obstetrician-gynecologists. AB - Threatened and actual medical malpractice claims associated with delivery of fertility-control services are studied in a national sample of 1,420 recently trained obstetrician-gynecologists who had been in practice an average of 3 years at the time of the survey. Nine percent of respondents report having been threatened with a fertility-control-related lawsuit, and 5.5% report being named as a defendant in such a suit. The types of services named most frequently as the basis of threatened lawsuits are sterilizations and abortions. In logistic regression analyses, variables found to significantly increase the risk of both threatened and actual lawsuits are number of years in practice and number of abortions provided during the last year of practice. Treatment of more minority patients significantly reduces the risk of both threatened and actual claims. Type of practice arrangement, physician gender, and attitudes toward physician patient communication are among the variables found not to affect the risk of litigation. Implications for provision of fertility-control services are discussed. PMID- 3352327 TI - Temporomandibular disorders. Variation in clinical practice. AB - This research describes the extent of variability in diagnosis and treatment of temporomandibular disorders (TMD) and relates this variability to treatment outcomes. A health maintenance organization sequentially referred 145 patients with orofacial pain and dysfunction to two TMD clinics. The two clinics differed substantially in their use of tomography (applied to 28% vs. 64% of all patients), and varied moderately in diagnoses assigned to the patient groups. There was large variation in selection of treatments including appliances for bruxism (64% vs. 5%), mandibular repositioning (10% vs. 25%), and joint stabilization (3% vs. 30%); anti-inflammatory medications (44% vs. 19%) and analgesics (16% vs. 2%); and subsequent referral for dental or orthodontic treatment (1% vs. 42%). The differences in diagnostic and therapeutic practice that were found were not associated with important differences in patient reported pain and dysfunction at 1-year follow-up. These data indicate the need for systematic approaches to identifying, evaluating, and modifying variation in health care practices for common presenting problems lacking reliable methods of evaluation and generally accepted clinical standards for choice of treatments. PMID- 3352329 TI - Statistical interactions in studies of physician utilization. Promise and pitfalls. AB - It has been suggested that use of interactive statistical models would greatly increase the proportion of variance accounted for by studies of physician utilization. The purpose of this paper is to evaluate and describe the benefits and pitfalls of using interactive statistical models of physician utilization. The paper presents Monte Carlo simulation data and real world data to determine how much more of the variance in physician utilization can be accounted for by interactive regression models. Results indicate that adding interaction terms is unlikely to produce large increases in variance accounted for. The usefulness of interactive models is particularly low when there is substantial measurement error in the predictor variables. Other advantages and disadvantages of interactive models are discussed, including 1) improved understanding, 2) inflation of alpha, 3) sensitivity to transformations and scale of measurement, and 4) confounding of interaction effects with nonlinear effects. PMID- 3352328 TI - Variations in pregnancy outcomes and use of obstetric procedures in two institutions with divergent philosophies of maternity care. AB - Pregnancy outcomes were compared between a stratified random sample of 796 women delivering a live birth at a maternity center (BMC) and a frequency matched sample of 804 women delivering a live birth at a tertiary hospital (TJUH) in 1977 1978. The relationship of use of obstetric procedures with pregnancy outcomes was investigated within and between the two samples. The neonatal morbidity rate, as measured by Hobel's neonatal risk score, was significantly higher and mean birth weights were lower at TJUH than at BMC when adjusted for institutional differences in use of obstetric procedures, medical-obstetric risk, and demographic characteristics. Conversely, the proportion of newborns with low 1 minute Apgar scores (fewer than seven) was significantly greater at BMC. The relationship of use of obstetric procedures with each outcome varied between the two institutions as well as across the three measures of pregnancy outcomes. The relationship of use of some procedures with each outcome may be explained in part by use of the procedure because of a suspected poor outcome of pregnancy, rather than an elevated risk of poor outcomes because of use of the procedure. Self selection of some patients to BMC cannot be ruled out as a possible explanation for institutional differences. PMID- 3352330 TI - Predictors of safety belt initiative by primary care physicians. A social learning theory perspective. AB - Even with the passage of state safety belt laws, primary care physicians can contribute to their patients' safety by brief interventions. The present study explores the prevalence of such action with adult patients and tests the power of constructs taken from social learning theory to explain physicians' behavior. These constructs included self-efficacy, personal behavior (self-modeling) and three outcome expectations--expectation of patient follow-through, health impact, and impact of health promotion on the practice. Data were taken from a survey of Texas family physicians prior to enactment of the state law (n = 209). History taking and advising were combined to form a single scale, "safety belt action." Prevalence of safety belt action was low. Overall, only 5% said they ask routinely about safety belts; 58.1% do not advise or discuss the risk even when they are aware of nonuse. Social learning theory variables accounted for 34% of the variance in safety-belt action after controlling for year of graduation in a hierarchical regression analysis. Self-efficacy was entered first, and it predicted 25% of the variance. The other social learning variables were entered together, and they predicted the additional 9% of the variance after controlling for year of graduation and self-efficacy. Of these other variables, only health impact was significant, however. These findings suggest several avenues for improving safety belt action and add evidence for the importance of outcome expectations over and above self-efficacy. PMID- 3352331 TI - Patient satisfaction with primary medical care. Evaluation of sociodemographic and predispositional factors. AB - As patient satisfaction has been demonstrated to influence certain health-related behaviors (e.g., compliance with medical regimens and use of medical services), research has attempted to identify its key determinants. Although the influence of patient characteristics often has been studied, attention has been focused on sociodemographic characteristics (e.g., age and sex) rather than attitudinal or situational factors (e.g., confidence in the medical care system and feelings of internal control) that may predispose one toward satisfaction with care received. Data to test the relative importance of these types of determinants were collected in a general household survey of 400 persons. The patient satisfaction scale developed and tested by Roghmann and his colleagues using nonmetric multidimensional scaling was used. Multiple regression analysis was performed on the data. Results show that certain predispositional factors (confidence in the community's medical care system, having a regular source of care, and being satisfied with life in general) are more important predictors of patient satisfaction than patient's age, sex, race, educational attainment, or income. PMID- 3352332 TI - Methods for measuring patient satisfaction with specific medical encounters. AB - This paper presents the results of two studies that compared methods for measuring patient satisfaction with specific medical encounters. One form used six-point response scales ranging from "very satisfied" to "very dissatisfied" (S6 scale); the other used five-point scales ranging from "excellent" to "poor" (E5 scale). Forms were assigned randomly to outpatients in fee-for-service (N = 136) and prepaid systems of care (N = 363) and were compared in terms of response variability, reliability, and validity. In both studies, the E5 scales showed greater response variability and better predicted whether patients intended to return to the same doctor in the future, recommend the doctor to a friend, and comply with the medical regimen. Reliability was satisfactory and did not differ between methods. Results are discussed in terms of their implications for constructing visit-specific satisfaction rating scales. PMID- 3352333 TI - The dental appointment and patient behavior. Differences in patient and practitioner preferences, patient satisfaction, and adherence. AB - Although the quantity and, in many cases, the quality of research on the practitioner-patient interaction has improved over the last 10-15 years, many related topics remain largely unexplored. The relationship of the similarity of practitioner and patient preferences to treatment adherence has not been carefully investigated, either in a medical or dental setting. This paper presents a study of patient and practitioner preferences for a dental appointment, and assesses the impact of their similarity on patient satisfaction with the appointment and adherence to the recommended treatment regimen. Results indicate that the similarity of patient and dental student preferences for an appointment is a very significant predictor of patient satisfaction with the appointment, reported improvement in oral hygiene behavior, and actual improvement in objective dental health. Patient satisfaction was, in turn, an independent predictor of reported behavior change and objective improvement in dental health. Similarity of patient and practitioner preferences for appointments should be studied more carefully in future doctor- and dentist patient interaction research, as it is a critical variable for understanding how the interaction experience is translated into patient behavior. PMID- 3352334 TI - Measuring the clinical appropriateness of the use of a procedure. Can we do it? AB - Increasing attention is being paid to data on geographic differences in population-based rates of use of medical and surgical procedures. To understand these differences and to determine what level of use is appropriate, a method is needed to judge the clinical appropriateness of services. We recently developed and tested such a method in two large, urban geographic areas. Eighty-one medical records from a randomly selected sample of 30 billing entities (46 physicians) who performed upper gastrointestinal endoscopy (UGIE) on Medicare patients were abstracted. Ninety-four percent of physicians who were asked agreed to participate. Reliability testing showed 99% agreement on items abstracted from a subset of records independently reviewed by two abstractors. Based on the abstractions, each patient could be assigned at least one (mean 2.2) specific clinical indication for which UGIE was performed. Using ratings derived from a previously held panel meeting, it was possible to evaluate the appropriateness of the indications for each UGIE. PMID- 3352335 TI - Effect of curtailed insurance benefits on use of mental health care. The Tenneco health plan. AB - This article presents the impact of a health insurance benefit redesign on utilization and costs for mental health care in a large corporation. The design change primarily limited coverage to 45 days of hospitalization and 20 outpatient visits. Group health insurance data before and after the benefit changes (effective January 1, 1984) were compared and analyzed. Per capita charges for mental health care between 1983 and 1985 decreased by 41%, from $89 to $53. Responses to the benefit modifications differed for inpatient and outpatient services. Inpatient costs and length of stay decreased dramatically, especially for dependents, while utilization rates remained about the same. Statistically significant increases occurred for outpatient care utilization and costs. PMID- 3352336 TI - [Aztreonam: prevention of bacteremia in urologic surgery in patients with urinary infection]. PMID- 3352338 TI - [Education and diabetes type II]. PMID- 3352337 TI - [Primary renal glycosuria and diabetes mellitus]. PMID- 3352339 TI - [AIDS phobia: a new facet of an old problem]. PMID- 3352340 TI - [A central file for clinical histories and clinical services of a hospital]. PMID- 3352341 TI - [Blood culture and pneumonia]. PMID- 3352342 TI - [Changes in calcitonin in hepatic cirrhosis]. PMID- 3352343 TI - [Human immunodeficiency virus infection in hemophiliacs]. PMID- 3352344 TI - [An epidemic outbreak of measles in La Victoria (Cordoba)]. PMID- 3352345 TI - [Multicenter study of acute myocardial infarction in Navarra in 1984 and 1985]. PMID- 3352346 TI - [Cerebral ischemia episodes in patients under 45 years of age. Retrospective study of 58 cases]. PMID- 3352347 TI - [Bromocriptine therapy in macroprolactinomas with extrasellar extension]. PMID- 3352348 TI - [Prognostic factors and predictive models of the different causes of failure in te induction of remission in acute nonlymphoblastic leukemia]. PMID- 3352349 TI - [Cerebral ischemia in patients under 45 years of age]. PMID- 3352350 TI - [Regression of renal lesions in hypertensive patients with renal insufficiency]. PMID- 3352351 TI - [Behcet's syndrome: intracranial hypertension without cerebral venous thrombosis]. PMID- 3352352 TI - [Methodology for the study of prognostic factors in oncology. I. Actuarial analysis]. PMID- 3352353 TI - [Acute myocardial infarct in Spain: comparison of 3 national multicenter studies with a multicenter study in an autonomous community]. PMID- 3352354 TI - [Feminizing multi-secreting corticoadrenal carcinoma]. PMID- 3352355 TI - [Amiodarone-induced hyperthyroidism resistant to treatment with thiol derivatives]. PMID- 3352356 TI - [Membraneous glomerulonephritis and adenocarcinoma of the prostate: association or coincidence?]. PMID- 3352357 TI - [Graves' disease and idiopathic thrombocytopenic purpura]. PMID- 3352359 TI - [Erythema nodosum and brucellosis]. PMID- 3352358 TI - [Respiratory depression and oral morphine]. PMID- 3352360 TI - [Use of sex hormones in pregnancy in Spain 1976-1984]. PMID- 3352361 TI - [Essential mixed cryoglobulinemia. A prospective study of 21 cases]. PMID- 3352362 TI - [Nontraumatic rhabdomyolysis: a clinical and morphological analysis of 53 cases]. PMID- 3352363 TI - [Hypodipsia in the elderly]. PMID- 3352364 TI - [Rapid correction of severe hyponatremia without neurological sequelae]. PMID- 3352365 TI - [Hyponatremia and the elevation of serum vasopressin in a hypothyroid patient]. PMID- 3352366 TI - [Polymicrobial infectious endocarditis in an intravenous drug addict]. PMID- 3352367 TI - [Program for improving the quality of epidemiologic information in sexually transmitted diseases]. PMID- 3352368 TI - [Contribution of gammography with gallium-67 to the study of pulmonary sarcoidosis]. PMID- 3352369 TI - [Determination of biventricular volumes using isotopic ventriculography. Physiologic response to exercise]. PMID- 3352370 TI - [Primary intestinal lymphoma of the western type. Retrospective study of 24 patients]. PMID- 3352371 TI - [Superior vena cava syndrome in a 78-year-old male with chronic lymphatic leukemia]. PMID- 3352372 TI - [Maternal smoking during pregnancy and risk of cancer in childhood]. PMID- 3352373 TI - [Late systemic vasculitis in a patient with Cogan's syndrome]. PMID- 3352375 TI - Update on antibiotics II. PMID- 3352374 TI - [Gingival and ocular metastasis as initial manifestation of a neoplasm of the lung: apropos of a case]. PMID- 3352376 TI - Antibiotic therapy of osteomyelitis in outpatients. AB - The therapy of osteomyelitis utilizing 481 courses of intravenous antibiotics in outpatients was analyzed to identify the types of bone infection most frequently treated by this form of therapy. The efficacy of this form of treatment is also discussed. PMID- 3352377 TI - [Reflections on the value of routine check-ups after curative treatment of breast cancer]. PMID- 3352378 TI - [Routine scintigraphy of the skeleton in breast cancer in Sweden 1986-1987]. PMID- 3352379 TI - [Best prognosis for the development of infants is to be born to non-smoking mothers]. PMID- 3352380 TI - [The knee joint is often the debut joint in rheumatoid arthritis]. PMID- 3352381 TI - [Treatment of massive digitalis poisoning with specific antibodies]. PMID- 3352382 TI - [Acquired toxoplasmosis is often mild but the symptoms can be difficult to interpret]. PMID- 3352383 TI - [Gastroscopy without duodenal biopsy--a waste of resources?]. PMID- 3352384 TI - [Prevention of endocarditis with antibiotics]. PMID- 3352386 TI - [HIV infection of the nervous system--pathogenesis clinical aspects and diagnosis]. PMID- 3352385 TI - [Orthopedic problems in bone dysplasias]. PMID- 3352387 TI - [Symptoms and behavior disorders among problem school children]. PMID- 3352388 TI - [Gluteal abscess shown to be a cholecystocutaneous fistula]. PMID- 3352389 TI - [Deglutition disorders caused by scleroderma was misinterpreted as achalasia cardiae]. PMID- 3352390 TI - [Is auditory screening of 4-year old children a good method for locating serous otitis which demands treatment?]. PMID- 3352391 TI - [One-session treatment of specific phobias--a rapid and effective method]. PMID- 3352392 TI - [Experiences with cases of diphtheria in Stockholm during the spring of 1986]. PMID- 3352393 TI - [Surgery of pancreatic cancer in Sweden--where and how?]. PMID- 3352394 TI - [Hypercalcemia with anemia and hypersedimentation--a case report]. PMID- 3352395 TI - [The All-Functions Ambulance system--a Swedish standard ambulance with new possibilities of pre-hospital care]. PMID- 3352396 TI - [Fight against drug abuse. The decision of the Judiciary Ombudsmen protects the rights of the patients]. PMID- 3352397 TI - [Progressive cerebral infarction caused by Borrelia infection]. PMID- 3352399 TI - [Extragenital endometriosis--differential diagnosis in pain of unknown origin]. PMID- 3352398 TI - [Tobacco or health: choose health]. PMID- 3352400 TI - [Endometriosis causing sigmoid perforation]. PMID- 3352401 TI - [Collagenous colitis--a lesser known cause of chronic diarrhea]. PMID- 3352402 TI - [Chronic urethral syndrome--a hidden female curse]. PMID- 3352403 TI - [Status epilepticus in adults--diagnosis and treatment]. PMID- 3352405 TI - [Surgical indication in acute myocardial infarction. Improved diagnosis and good surgical results in rupture of the heat septum]. PMID- 3352404 TI - [Thrombolysis in acute myocardial infarction. Chemical methods do not yield accurate diagnosis of reperfusion in intravenous streptokinase therapy]. PMID- 3352406 TI - [5-8 years after sterilization: many young people regret their decision]. PMID- 3352407 TI - [Chronic compartment syndrome of the forearm extensors]. PMID- 3352408 TI - [Repeated dosage of activated charcoal--an effective treatment in theophylline poisoning]. PMID- 3352409 TI - [PTA--is often a suitable treatment of atherosclerosis of the pelvic vessels]. PMID- 3352410 TI - [HIV and intravenous drug abuse]. PMID- 3352411 TI - [Which health care workers should be tested for HIV-infection]. PMID- 3352412 TI - [Surgical methods in spinal neurogenic bladder disorders]. PMID- 3352413 TI - [Anisakiasis--an inflammatory condition caused by roundworms from raw fish]. PMID- 3352414 TI - [HIV screening of pregnant women--results and experiences after 1 year]. PMID- 3352415 TI - [HIV status and risk behavior among imprisoned intravenous drug addicts in Stockholm]. PMID- 3352416 TI - [A case report of chronic abdominal pain with unexpected course]. PMID- 3352417 TI - [Intracranial vasculitis turns out to be brain abscess]. PMID- 3352419 TI - [HIV and hospital personnel]. PMID- 3352418 TI - [A survey of accidents in elementary school. Can occupational legislation include pupils?]. PMID- 3352420 TI - [The shoulder at a district medical officer's clinic. Refined diagnosis, treatment and follow-up]. PMID- 3352421 TI - [Neuroleptic malignant syndrome with rhabdomyolysis and compartment syndrome]. PMID- 3352424 TI - [Acetarsol-an organic arsenic compound with toxic effect on the optic nerve]. PMID- 3352422 TI - [Oral contraceptives causing chorea in a young woman]. PMID- 3352426 TI - [Immigrants consult health care centers more often than Swedes]. PMID- 3352423 TI - [Perinatal listeriosis--a nosocomial outbreak in an obstetric department]. PMID- 3352425 TI - [Acute psychosis as the major symptom in a case of hypothyroidism difficult to diagnose]. PMID- 3352427 TI - [Psychiatric sequels after extreme stress--an aspect of refugee psychiatry]. PMID- 3352428 TI - [Toxic effects on the heart in tricyclic antidepressant poisoning--a case report and therapy]. PMID- 3352429 TI - [Papillary cystic pancreatic tumor in a girl--a case report with cytological diagnosis]. PMID- 3352430 TI - [Swedish Obese Subjects--an intervention study on obesity]. PMID- 3352431 TI - [The nursing situation in a community in Stockholm: the home care services are heavily overloaded during the reorganization of geriatric nursing]. PMID- 3352432 TI - Spontaneous tonsillar hemorrhage. AB - Spontaneous tonsillar hemorrhage (STH) of non-iatrogenic causes occurs most frequently from infection. Infection can lead to erosion into a major vessel, such as the carotid artery or a smaller peripheral tonsil vessel. Whereas fatal erosion into a major vessel from a deep neck abscess was relatively common in the past, it is rare since the advent of antibiotics. Spontaneous tonsillar hemorrhage, when it does occur, appears to occur most commonly in a peripheral tonsil vessel from bacterial tonsillitis. Medical records of 860 patients with conditions considered to be susceptible to STH were reviewed. Ten cases of STH were identified. All were from peripheral tonsil vessel hemorrhage; none was secondary to major vessel erosion. Bacterial tonsillitis was the most common cause of STH and occurred in 8 of 10 cases. This condition accounted for an incidence of STH in tonsillitis of 1.1%. A history of chronic tonsillitis appeared to predispose a patient to STH. Other causes of STH were infectious mononucleosis and neoplasm. Seven of the ten peripheral STHs presented with bleeding from an obvious venous source. The other three patients had significant hemorrhages which led to arteriography. Arteriograms are indicated in patients with clinical features suggesting possible major vessel erosion or in those patients where significant bleeding is not from an obvious peripheral source. A peripheral STH can be successfully managed with local intervention and tonsillectomy. PMID- 3352435 TI - Paralyzed eyelids reanimated with a closed-eyelid spring. AB - Implantation of gold weights and open wire springs to close the eyelid have provided good corneal protection in selected patients with eyelid paralysis. These techniques, however, do not overcome lower eyelid drooping. The closed eyelid spring technique was developed to address this problem, and, to date, the author has implanted 27 closed-eyelid springs. This technique has reestablished a voluntary blink, provided corneal protection, and effectively held the lower lid in a relatively normal position in 25 of 27 patients. This report describes patient selection, surgical technique, and results of implanting closed-eyelid springs to reanimate paralyzed eyelids. PMID- 3352433 TI - Phototherapy with the argon laser on human melanoma cells "sensitized" with rhodamine-123: a new method for tumor growth inhibition. AB - Laser photodynamic therapy of superficial malignancies is a promising new approach that will become clinically useful when fluorochromes with high tumor specificity and low toxicity to normal tissues are identified. We recently reported that the mitochondrial dye, Rhodamine-123 (Rh-123), at nontoxic doses, is an effective sensitizing agent for argon laser treatment of human squamous carcinoma and melanoma cells in vitro. We now report the complete inhibition of in vivo tumor development by human M24 melanoma cells transplanted subcutaneously into nu/nu mice after exposure to 1 microgram/ml of Rh-123 for 1 hour and treatment with an argon laser at nonthermal temperatures of 36 to 40 degrees C. Significant in vivo growth was observed for all control tumors. These results demonstrate that Rh-123 enhances the tumoricidal effects of the argon laser at nonthermal temperatures and provides evidence that effective photodynamic therapy may be possible in vivo with the new fluorochrome Rhodamine-123. PMID- 3352434 TI - The prevention of carotid artery rupture with isobutyl-2-cyanoacrylate. AB - Carotid artery exposure and rupture is one of the most feared complications of head and neck surgery. The ideal method for preventing rupture of an exposed artery should be easy to perform, safe, effective and should spare local and regional flaps for later use in reconstruction. Isobutyl-2-cyanoacrylate (Bucrylate) is a commercially available compound that appears to meet these criteria. Test animals were divided into two groups. The carotid arteries of 12 dogs (group A) were exteriorized bilaterally and coated with Bucrylate unilaterally. Group B (four dogs) underwent the same procedure except that the vessels were bilaterally coated. Wounds were dressed twice daily with moist-to dry gauze. No antibiotics were given. Nine of the 12 unprotected arteries in group A ruptured within 2 weeks, and one unprotected artery ruptured on postoperative day (POD) 29. Two dogs healed over both vessels. In group B, three dogs ruptured their arteries within 2 weeks. One dog healed over both vessels. Gross and histologic examination of the arteries showed a striking difference between coated and uncoated vessels. We believe that Bucrylate and cyanoacrylate adhesives hold promise in the clinical protection of exposed carotid arteries. PMID- 3352436 TI - Sensorineural hearing loss in sickle cell crisis. AB - The present investigation examines the effects of sickle cell crisis on peripheral auditory function and auditory brainstem response (ABR). The study includes 10 homozygous sickle cell anemia patients with documented sickle cell (SS) hemoglobin. Testing was performed during the crisis and 1 month after it subsided. Unilateral high frequency hearing loss was found in three patients but persisted in only one of them. Abnormal ABR tracings occurred in four patients but reversed to normal in one of them. The study suggests a trend toward increased incidence of sensorineural hearing loss (SNHL) and ABR changes as frequency and severity of crisis episodes increases. The relationship between SNHL and ABR is analyzed and discussed. PMID- 3352438 TI - Acceptability ratings of tracheoesophageal speech. AB - Thirty-one naive listeners rated the intelligibility and acceptability of tracheoesophageal, esophageal, and normal laryngeal speech of 15 adult speakers. Intelligibility was measured using a multiple-choice word test while acceptability was rated on a seven-point equal-appearing interval scale. Judgments were made on the features of fluency, pitch/quality, speech rate, inflection, and overall acceptability. Tracheoesophageal speech was found not to differ significantly from normal speech in intelligibility, rate, and inflection, but was less acceptable for fluency, pitch/quality and overall acceptability. Tracheoesophageal speech was more acceptable than esophageal speech for all features measured. PMID- 3352437 TI - Anomalies of the middle ear. AB - Malformations of the ossicles in 52 ears of 48 patients were analyzed on the basis of surgical findings. The external meatus of each of these ears was patent. The long process of the incus and the stapes are frequently involved in this series of observations. There are distinct groups of ossicular anomalies, in each of which patients show similar degrees of hearing loss and ossicular findings. These include spindle handle, malleus bar, and dislocated annulus. Spindle handle gets its name from the shape of the malleus handle. There is disconnection between the long process of the incus and the capitulum of the stapes. Malleus bar is a kind of malleus fixation, in which a small bony bar connects the tip of the malleus handle to the posterior wall of the tympanic cavity. In the dislocated annulus, the annulus is dislocated cranially in relation to the middle ear structures. Anomalies of the ossicle are usually present. Surgical repairs for these conditions are discussed. PMID- 3352439 TI - Vocal cord abduction rehabilitation by nervous selective anastomosis. AB - Laryngeal reinnervation procedures were performed on 15 dogs. An anastomosis was performed between a selected motor branch of the ansa hypoglossi and the posterior cricoarytenoid nerve. The results were analyzed endoscopically, electromyographically, and histologically. Results were satisfactory in 12 cases. The methods and results have been compared with those obtained using other reinnervation techniques. PMID- 3352440 TI - Electromyographic rehabilitation of facial function and introduction of a facial paralysis grading scale for hypoglossal-facial nerve anastomosis. AB - For reinnervation of facial paralysis, the XII-VII nerve anastomosis provides tone and mass contraction but rarely allows selective muscle control. The efficacy of EMG rehabilitation was evaluated in 30 patients who had no coordinated control of facial muscles. EMG signals from bilateral homologous facial muscle sites were converted into computer-compatible waveform traces and displayed on a video monitor. This facilitated modification of neuromuscular responses using behavioral shaping techniques. A six-point Facial Nerve Grading Scale was introduced for hypoglossal-facial nerve anastomosis to assess the results of EMG rehabilitation. Rehabilitation lasted from 3 to 18 months. Ten patients (33%) achieved the highest possible grading (II) with symmetry and synchrony of function and spontaneity of expression; 17 (57%) reached grade III, which allowed voluntary control of eye and mouth function; 3 (10%) showed minimal gains. It is suggested that neural plasticity allows therapeutic manipulation of central facilitory and inhibitory mechanisms, and possible unmasking of neural connections between the ipsilateral VII and XII nerve motor nuclei which leads to improved facial function. PMID- 3352442 TI - Motions of the posterior pharyngeal wall in swallowing. AB - The motions of the posterior pharyngeal wall during swallowing were studied in four asymptomatic males using a new method for videoradiography. Radiopaque markers of 4 mm diameter were affixed to the pharyngeal wall by suction. Ventrodorsal and axial components of motion were measured frame by frame. Large axial motions occurred during the pharyngeal stage of swallowing. Cephalad displacement of each marker occurred early and was followed by caudad motion. Within the pharyngoesophageal segment, there were cephalocaudal motions measuring as much as 25 mm. A late caudad motion beyond the reference position was observed in this segment in two participants. This late motion may play a role in passing the bolus through the pharyngoesophageal segment. The findings support the concept of an "engulfment" mechanism in pharyngeal kinesiology. PMID- 3352441 TI - Autosomal dominant osteopetrosis: an otoneurological investigation of the two radiological types. AB - Otoneurological examination was performed on 14 patients with autosomal dominant osteopetrosis. Eight patients had radiological type I osteopetrosis, characterized by a pronounced osteosclerosis of the skull and an enlarged thickness of the cranial vault. Six patients had type II, in which osteosclerosis is most pronounced at the base of the skull. All investigated patients except one had otoneurological manifestations, but only two of of the 14 had otoneurological complaints. Symptoms were related to radiological types. Involvement of the trigeminal nerve was seen only in type I, whereas involvement of the facial nerve was found primarily in type II. Conductive hearing loss was particularly common in type I, and may reflect a high frequency of otosclerosis. Tomography of the petrous bones showed a significant narrowing of the internal acoustic meatus in type I (p less than 0.01) when compared to normal controls, but no significant narrowing in type II. PMID- 3352443 TI - Metastatic thymoma to the head and neck. AB - Malignant thymoma is a mediastinal tumor which spreads primarily by local invasion. Spread to regional lymph nodes and distant organs is variable. The most common sites of metastasis in the head and neck region are the supraclavicular nodes and the brain. Cervical lymph node metastasis as the presenting symptom of malignant thymoma has not yet been reported in the otolaryngologic literature. We present three cases of metastatic thymoma to the neck from a series of 28 thymomas, ten of which were malignant. The clinical presentation, histopathological features, therapy, and prognosis of malignant thymomas are discussed. PMID- 3352444 TI - Pediatric upper airway obstruction due to ectopic thyroid: classification and case reports. AB - Few clinical situations can be as frightening, challenging, and as rewarding as stabilizing the airway of a child. Most causes of pediatric upper airway obstruction are well recognized, often discussed in the literature, and commonly encountered in practice. However, ectopic thyroid (i.e., thyroid tissue found in places other than its normal location) may be an unusual cause of pediatric upper airway obstruction with which the clinician may not be familiar. The resulting airway obstruction may be slow or rapid in onset, total or partial, and the relationship of the thyroid to the airway may be clear or obscure. Two cases of obstructing ectopic thyroid are presented which demonstrate the spectrum within which this form of airway obstruction may occur. One case is the first reported example in the English literature of pediatric intratracheal thyroid. A review of the literature is also presented. Four types of ectopic thyroid (lingual, sublingual, thyroglossal, and intralaryngotracheal) are illustrated and discussed in relation to their effect upon the pediatric upper airway. The authors also review the developmental anatomy of the thyroid and present two major theories regarding the development of intralaryngotracheal thyroid. The possible etiologies of the other ectopic forms are also discussed. PMID- 3352445 TI - Laryngeal/voice findings in patients with velopharyngeal dysfunction. AB - It is reported frequently that individuals with palatal clefts have a high occurrence of laryngeal/voice symptoms. It has been speculated that vocal pathology in this population is the result of laryngeal compensation for abnormal velopharyngeal valving. This paper describes the prevalence of laryngeal/voice findings in a group of 85 patients referred for multimethod evaluation of velopharyngeal dysfunction. Forty-one percent of the patients had auditorily perceived voice symptoms and/or observable laryngeal abnormalities. Twenty-one percent of the patients had vocal fold nodules or thickened vocal folds. There was no clear relationship between laryngeal/voice findings and nasoendoscopic or aerodynamic assessments of velopharyngeal dysfunction. However, there was a significant relationship between laryngeal/voice findings and estimated subglottal pressure. Patients with laryngeal/voice findings (with or without nodules) had average estimated subglottal pressure values which were outside the normal range more often than patients without laryngeal/voice findings. These results suggest patients referred for assessment of velopharyngeal dysfunction should receive a comprehensive evaluation which includes screening laryngeal structure and function. PMID- 3352446 TI - The temporal fossa in head and neck reconstruction: twenty-two flaps of scalp, fascia, and full-thickness cranial bone. AB - We reviewed 22 consecutive flaps based on the blood supply of the temporal fossa. Our purpose was to demonstrate reliability of the vascular supply and to illustrate the versatility of these tissues for reconstruction of specialized structures, including eyelids, eyebrow, ear, lips, oral lining, orbit, and mandible. For these complex problems, all but one patient required multiple-stage surgery to obtain their final aesthetic and functional results. All flaps proved reliable and versatile. Their advantages include proximity to the reconstructive site, ease of bilateral reconstructions, and well-camouflaged donor deficit. In particular, the ability to transfer vascularized full-thickness cranial bone for total or bilateral mandibular reconstructions presents an additional possibility for this difficult problem. We conclude that the reconstructive potential of these flaps is limited only by the surgeon's ingenuity. PMID- 3352447 TI - Modification of the deltopectoral flap for pharyngoesophageal reconstruction. AB - These modifications minimize flap loss, fistulae, and stenosis, and make the final stage easier to perform. The need for periodic dilation with Maloney dilators may be required; however, we do not consider this a significant complication. The goal is a predictable result with a low complication rate so that oral feedings can begin 5 weeks after laryngopharyngectomy, and postoperative radiotherapy may be started at 6 weeks. The need for three stages may appear excessive; however, three planned stages are better than three or more unplanned stages that result in flap loss or dehiscence. PMID- 3352448 TI - Total Patient Care Conference. PMID- 3352449 TI - Remote biomedical spectroscopic imaging of human artery wall. AB - We discuss a general technique, laser spectroscopic imaging (LSI), remote acquisition of spectroscopic images of biological tissues and tissue conditions. The technique employs laser-induced spectroscopic signals, collected and transmitted via an array of optical fibers, to produce discrete pixels of information from which a map or image of a desired tissue characteristic is constructed. We describe a prototype LSI catheter that produces spectral images of the interior of human arteries for diagnosis of atherosclerosis. The diagnostic is based on the fact that normal artery wall and atherosclerotic plaque exhibit distinct fluorescence spectra in the 500-650 nm range when excited by 476-nm laser light; the fluorescence from blood is minimal. The catheter is composed of 19 optical fibers enclosed in a transparent, protective shield. Argon ion laser radiation is used for excitation, and an optical multichannel spectral analyzer is used for detection. Sequential sampling is used to minimize crosstalk among fibers and reduce blurring of the image. Computer-processed 19-pixel spectroscopic images are produced of fresh cadaver artery in vitro. Regions of normal tissue, plaque, and blood are identified, and the diagnoses are confirmed histologically and by direct spatial correlation. The results demonstrate the concept of using this laser catheter system for real-time imaging. PMID- 3352450 TI - New developments in laser cardiology. PMID- 3352451 TI - Phycocyanin: laser activation, cytotoxic effects, and uptake in human atherosclerotic plaque. AB - Phycocyanin is a phycobiliprotein with peak absorption at 620 nm. The laser activation, cytotoxic effects, and uptake into atherosclerotic plaque of phycocyanin was studied. Optimal activation was produced by argon dye laser at 0.5 W and a total energy dose of 300 J/cm2 at 620 nm and 650 nm, irradiated through blood with a hematocrit of 8%. Activation was evidenced by reduction of optical density by 0.3 units at 340 nm caused by oxidation of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) in a buffered reaction solution containing 0.1 mg/ml of phycocyanin. Cytotoxicity was evaluated by measuring viability of mouse myeloma cells in culture after incubation with phycocyanin (0.25 mg/ml) and irradiated by 300 J/cm2 at 514 nm. After 72 hours post-treatment the cells showed 15% viability compared to 69% and 71% for control cells exposed to laser only or phycocyanin only, respectively. Atherosclerotic artery segments obtained within 5 hours postmortem were perfused with 0.1 mg/ml phycocyanin in oxygenated Krebs Ringer solution at 30 mm Hg for 5 minutes followed by washout with phycocyanin-free Krebs for 10 minutes. Artery sections examined histologically by light and fluorescence microscopy showed specific fluorescence localization within the plaque particularly at the elastic laminae and to a larger extent at the internal elastic lamina but not in the medial muscle layer. In conclusion, phycocyanin is a cytotoxic photosensitizer that exhibits specific binding to plaque and is activated at a wavelength minimally absorbed by blood. These properties suggest potential therapeutic use for plaque localization and regression. PMID- 3352452 TI - Effect of pulse duration on selective ablation of atherosclerotic plaque by 480- to 490-nanometer laser radiation. AB - The effect of varying pulse duration on selective ablation of human arterial plaque was evaluated by measuring ablation thresholds and ablation efficiencies on fresh human fibrofatty plaque, calcified plaque, normal intima, deep media, and adventitia using 480- to 490-nm laser radiation at 1, 8, and 50-microseconds pulse durations. For all tissues examined, the ablation threshold energy increased with increasing pulse duration, but the threshold for normal tissue ablation was approximately twice that of plaque at all pulse durations. Ablation efficiency was studied at a fluence that was twice the ablation threshold for plaque. For those fluences, normal intima had detectable ablation only at 50 microseconds. The ablation efficiency of fibrofatty plaque was minimally reduced with prolongation of pulse duration; however, there was a substantial decrease in the ablation efficiency of calcified plaque when the pulse duration was lengthened from 8 to 50 microseconds. These data show significant selective ablation of fibrofatty and calcified plaque at 1, 8, and 50 microseconds and suggest that the optimal pulse width for selective ablation of all plaque in the 480- to 490-waveband is less than 50 microseconds. PMID- 3352453 TI - Mechanism of tissue fusion in argon laser-welded vein-artery anastomoses. AB - The mechanism of laser vascular tissue welding remains unknown. This study compared the acute tissue response and long-term healing of sutured and laser welded anastomoses of vein segments used to bypass ligated canine femoral arteries. For each procedure, one anastomosis was formed using running 6-0 polypropylene suture (control), and the other anastomosis was formed using argon laser tissue welding (experimental). The vein grafts were harvested at 4 (n = 2), 8 (n = 1), 12 (n = 1), and 16 (n = 2) weeks, and selected samples were evaluated by histologic examination, electron microscopy, tensile strength testing, and by measuring the formation of [3H]hydroxyproline as an index of collagen synthesis. Examination of successful laser fusions immediately after they were formed showed bonding of collagen to collagen and elastin to collagen. Follow-up evaluations showed that the precision of tissue apposition affected the rate of healing and tensile strength. Laser-welded anastomoses demonstrated a progression of healing similar to sutured repairs, with remodeling of fibrous tissue and collagen being the primary component of weld integrity. This study demonstrates that sutured and argon laser-welded vein-artery anastomoses heal comparably up to 16 weeks postoperatively, and that laser welding is a satisfactory alternative to sutured anastomoses. PMID- 3352454 TI - [Campylobacter pylori--status of knowledge from the morphologic viewpoint]. AB - The morphological alterations of the gastric mucosa due to Campylobacter pylori (C.p.) were examined with high resolution light microscopy, scanning electron microscopy, and transmission electron microscopy. On the ultrastructural level the number and distribution of bacteria were correlated to the extent of the inflammatory resp. degenerative epithelial alterations. Intestinal metaplasia was always free of bacteria, even with strong colonization of the residual mucosa. In comparison to the gastric mucosa in the IM the cellular disintegration was less strongly developed. The topographical distribution of C.p. was studied on two ulcer resection specimens and documented by means of "campylobacter-mapping". Contrary to the subjective impression made by stomach biopsies, the bacterial colonization examined was not patchy, but rather it was evenly distributed. The association between C.p. and duodenal ulcer, made in most literature, relies primary on cultural, or morphological studies of the antrum mucosa, thereby actually representing the correlation of C.p. to the accompanying gastric inflammation. An analysis of the detection methods--morphological, cultural, and the urease-test--confirms the significance of morphological methods in the diagnosis of C.p.-infection. PMID- 3352455 TI - Renal effects of low-dose aminophylline and enprofylline in newborn rabbits. AB - Renal function was studied in 15 newborn New Zealand rabbits administered either 0.6 mg/kg enprofylline intravenously. Each animal acted as its own control. Glomerular filtration rate (GFR) and renal blood flow (RBF) were assessed by the clearances of inulin and para-aminohippuric acid, respectively. Enprofylline, a xanthine with low adenosine antagonistic properties, did not modify urine flow rate, GFR, RBF, renal vascular resistance, filtration fraction, sodium and potassium urinary excretion, whereas administration of theophylline, a potent adenosine antagonist, was associated with a significant increase in diuresis, renal vascular resistance and filtration fraction. The differences observed in the renal effects of theophylline and enprofylline strongly support the view that 1) the renal actions of micromolar concentrations of theophylline are mediated by an antagonism with endogenous renal adenosine; 2) renal adenosine could play a physiological role in the regulation of renal hemodynamics. PMID- 3352456 TI - Characterization of [3H]forskolin binding sites in the iris-ciliary body of the albino rabbit. AB - [3H]Forskolin binding sites were identified using membranes prepared from the iris-ciliary body of adult, albino rabbits. Scatchard analysis of saturation binding experiments demonstrated that [3H]forskolin bound to a single population of high affinity sites. The Kd and Bmax values were 8.7 +/- 0.9 nM and 119.0 +/- 30.9 fmol/mg prot. using membranes prepared from frozen tissue and 17.0 +/- 6.2 nM and 184.4 +/- 47.2 fmol/mg prot. using fresh tissue. The binding of [3H]forskolin was magnesium-dependent. The Bmax was enhanced by sodium fluoride and Gpp(NH)p, a nonhydrolyzable guanine nucleotide analog. Forskolin was the most potent inhibitor of [3H]forskolin binding; two commercially-available analogs were weaker inhibitors. In an adenylate cyclase assay, there was the same rank order of potency to enhance enzyme activity. Based upon binding affinities, magnesium-dependence, sensitivity to sodium fluoride and Gpp(NH)p, rank order of potencies of analogs and correlation of binding with adenylate cyclase activity, these studies suggest that the [3H]forskolin binding site in the iris-ciliary body is similar to the binding site in other tissues. PMID- 3352457 TI - In vivo binding of [18F]GBR 13119 to the brain dopamine uptake system. AB - Regional rat brain uptake of [18F]GBR 13119, a high specific activity, positron emitter labeled derivative of the potent dopamine uptake antagonist GBR 12935, is reported. Striatum to cerebellum ratios of 3 are obtained at 90 minutes post injection. Specific binding in striatum can be blocked by pretreatment with dopamine uptake system antagonists (mazindol, nomifensine) but not with receptor antagonists (spiperone, flupenthixol). [18F]GBR 13119 is proposed as a new positron-emitting radioligand for in vivo PET studies of the pre-synaptic dopamine uptake system. PMID- 3352459 TI - Binding of [3H]forskolin to solubilized preparations of adenylate cyclase. AB - The binding of [3H]forskolin to proteins solubilized from bovine brain membranes was studied by precipitating proteins with polyethylene glycol and separating [3H]forskolin bound to protein from free [3H]forskolin by rapid filtration. The Kd for [3H]forskolin binding to solubilized proteins was 14 nM which was similar to that for [3H]forskolin binding sites in membranes from rat brain and human platelets. Forskolin analogs competed for [3H]forskolin binding sites with the same rank potency in both brain membranes and in proteins solubilized from brain membranes. [3H]forskolin bound to proteins solubilized from membranes with a Bmax of 38 fmol/mg protein which increased to 94 fmol/mg protein when GppNHp was included in the binding assay. In contrast, GppNHp had no effect on [3H]forskolin binding to proteins solubilized from membranes preactivated with GppNHp. Solubilized adenylate cyclase from non-preactivated membranes had a basal activity of 130 pmol/mg/min which was increased 7-fold by GppNHp. In contrast, adenylate cyclase from preactivated membranes had a basal activity of 850 pmol/mg/min which was not stimulated by GppNHp or forskolin. Thus, the number of high affinity binding sites for [3H]forskolin in solubilized preparations correlated with the activation of adenylate cyclase by GppNHp via the guanine nucleotide binding protein (GS). PMID- 3352458 TI - In vivo depression of reserve albumin binding capacity by cadmium: a preliminary evaluation. AB - The effect of cadmium upon the depression of reserve albumin binding capacity (%RABC) was investigated in male, New Zealand white rabbits at daily dosages of 0.65 mg and 0.90 mg Cd/kg body weight. Correlations of % RABC to the duration of exposure were strongest at the higher dosage. After 30-35 days exposure, the decline in % RABC was partially reversed. Levels of total protein in urine increased sharply within a few days after the % RABC had been reduced by cadmium to their lowest values. PMID- 3352460 TI - Hydroperoxide and cigarette smoke induced effects on lung mechanics and glutathione status in rat isolated perfused and ventilated lungs. AB - The effects of t-butylhydroperoxide (TBH) and cigarette smoke on lung mechanics (CDYN and RL) and glutathione status (GSH) were studied using an isolated perfused and ventilated rat lung preparation. TBH (200, 400, 1000 microM) infused via the pulmonary circulation caused a dose-related bronchoconstriction. The lung GSH-levels were also significantly reduced. Pretreatment of rats with diethylmaleate (DEM) potentiated the TBH elicited bronchoconstriction. DEM (1 mM) infused into the pulmonary circulation caused an almost complete depletion of GSH content but no effects on lung mechanics were seen. Indomethacin (2.8 and 28 microM) infusion attenuated TBH (400 microM) induced bronchoconstriction. These findings suggest that the TBH induced bronchoconstriction is at least partly mediated via arachidonic acid metabolites. When TBH was administered intratracheally, weak and not dose-related bronchoconstriction was observed even though doses higher than those given intravascularly were used. However, the GSH content of the lungs was markedly decreased. Cigarette smoke caused weak if any effects on lung mechanics but significantly decreased lung GSH-content. PMID- 3352461 TI - Effect of indomethacin on modest pressure natriuresis in chloralose-anesthetized, non-laparotomized dogs. AB - To determine if indomethacin (indo) would attenuate the effects of changed renal perfusion pressure on sodium excretion as reported by others, we performed clearance studies in chloralose-anesthetized dogs without the major stress of laparotomy. Mean renal arterial pressure was varied by a balloon-tipped catheter indwelling the aorta suprarenally. With pressure decreases to mean values above 85 mm Hg during isotonic saline infusion, sodium output decreased only by 10.7 +/ 2.4% per 10 mm Hg pressure decrease without indo pre-treatment but decreased by 22.0 +/- 3.8% per 10 mm Hg pressure decrease with indo pre-treatment. The greater, rather than lesser, pressure effect on excretory function after indo in these experiments with chloralose anesthesia suggest that renal prostaglandin (PG) activity does not mediate normally pressure natriuresis. Instead, the data suggest that, in the absence of major stress, the renal pressure effects on excretory function may become more sensitive after indo. In addition, we postulate that the normal acute pressure natriuresis may be modest and may average no more than 20% change for each 10 mm Hg change in mean pressure above 90 mm Hg when stress is minimal and when vasoactive preglomerular autoregulation is nearly perfect. This is a phenomenon which keeps intrarenal tissue pressure and urine output relatively constant with arterial pressure elevations. PMID- 3352463 TI - Presynaptic inhibition of nigrostriatal dopamine release in the mouse: lack of cross tolerance between apomorphine, GBL and CGS 10746B. AB - Acute parenteral injections of apomorphine, gamma-butyrolactone (GBL) and CGS 10746B decreased dopamine release in the mouse nigrostriatal pathway as evidenced by decreases in striatal 3-methoxytyramine levels. In a 7 day treatment paradigm, the effects of acute apomorphine, GBL and CGS 10746B were unaltered in animals treated b.i.d. with GBL (500 mg/kg, i.p.). In contrast, the actions of acute CGS 10746B expressed a complete tolerance in mice treated b.i.d. with CGS 10746B (20 mg/kg, i.p.), while the actions of acute apomorphine or GBL were similar in the chronic saline and chronic CGS 10746 groups. These data show that the inhibition of striatal dopamine release by CGS 10746B is susceptible to tolerance. In addition, the lack of cross tolerance between GBL, apomorphine and CGS 10746B suggests independent sites of action for these agents in inhibiting dopamine release. PMID- 3352462 TI - Evidence for suppression of serum LH without elevation in serum estradiol or prolactin with a brain-enhanced redox delivery system for estradiol. AB - We developed a redox system for brain-enhanced delivery of estradiol based on an interconvertible dihydropyridine in equilibrium pyridinium salt carrier. Estradiol (E2), when combined with the lipoidal carrier, readily crosses the blood-brain barrier. The carrier, when oxidized, reduces the rate of exit of the estradiol-carrier complex from the brain. Subsequent hydrolysis of the carrier provides sustained production of estradiol in the brain. The aim of the study was to evaluate the effects of single vs. multiple injections of the estradiol chemical delivery system (E2-CDS) on both central and peripheral estrogen responsive tissues. Ovariectomized Sprague-Dawley rats received an intravenous injection of E2-CDS at 10, 33, 100 or 333 micrograms/kg BW or the drug vehicle, dimethyl sulfoxide (DMSO; 0.5 ml/kg) every 2 days for 7 injections (2 weeks) or a single injection only at 2 days before sacrifice. With a single injection, E2-CDS did not affect serum luteinizing hormone (LH) levels at the 10 micrograms/kg dose but caused a dose-dependent reduction in serum LH of 39-52% at the dose range of 33 to 333 micrograms/kg. By contrast, multiple injections of E2-CDS caused a 32 to 76% reduction in serum LH levels at doses ranging from 10 micrograms/kg to 333 micrograms/kg. Additionally, multiple doses of E2-CDs caused a dose-dependent reduction in body weight at the 10 and 33 micrograms/kg doses with the higher doses causing no further weight reduction. For both single and multiple dosage groups, serum E2 levels remained unchanged after doses of E2-CDS of 10 and 33 micrograms/kg, then increased to 21 pg/ml for the single dosage group and to 23 pg/ml for the multiple dosage group at the 100 micrograms/kg dose, and to 59 pg/ml for singly-injected rats and 60 pg/ml for multiply-injected rats at the 333 micrograms/kg dose. Serum prolactin concentrations were closely correlated with serum E2 levels for both the single and multiple dose groups. These data reveal that a single or multiple doses of E2-CDS can reduce serum LH levels without elevating serum E2 or prolactin concentrations, supporting the concept of brain enhanced delivery of estradiol with an estradiol chemical delivery system. PMID- 3352464 TI - Effect of ethanol on serum electrolytes and osmolality. AB - Rats and rabbits were injected ethanol 2 g/kg intraperitoneally. One hour after injection blood was analyzed for serum electrolytes and osmolality. Administration of ethanol caused decrease in serum sodium (p less than 0.0005), potassium (p less than 0.0005), calcium (p less than 0.0005), chloride (p less than 0.005), magnesium (p less than 0.0005) in rabbits. Further studies of intraperitoneal administration of ethanol in rats showed decrease in concentration of sodium (p less than 0.025), potassium (p less than 0.025), calcium (p less than 0.01) chloride (p less than 0.005) magnesium (p less than 0.005), phosphorus (p less than 0.025) and glucose (p less than 0.005). Administration of ethanol caused an increase in serum osmolality in both rabbits and rats (p less than 0.005, p less than 0.05). It is concluded that ethanol ingestion is probably the commonest cause of the hyperosmolar state. Although the osmotic and sedative effects of ethanol are pharmacologically unrelated, the presence of ethanol should be considered in comatose patients in whom the measured plasma osmolality appreciably exceeds that predicted on the basis of plasma glucose, urea and electrolytes concentration. PMID- 3352465 TI - Nigrostriatal dopaminergic activity is increased during exhaustive exercise stress in rats. AB - Exercise capacity is influenced by both increases and decreases in central dopaminergic activity. To investigate the effects of exercise stress on intracerebral dopamine metabolism, rats were run on a motor driven treadmill at 37 m/min for varying times up to exhaustion at 19.6 +/- 0.6 min. Dopamine, DOPAC, and HVA concentrations in striatum, brain stem, and hypothalamus increased towards exhaustion. 5-HIAA concentrations increased in striatum whereas norepinephrine concentrations decreased in hypothalamus. The results indicate that delayed increases in dopaminergic activity occurs during exercise. These, and other observations indicate that central dopaminergic activity modulates exercise performance. PMID- 3352466 TI - Inhibition of platelet [3H]-imipramine binding by human plasma protein fractions. AB - Inhibition of high-affinity [3H]-imipramine binding to platelet membranes by human plasma fractions and isolated plasma proteins was investigated. Several plasma proteins were found to contribute to the observed apparent inhibition and this contribution was assessed in terms of inhibitor units. Alpha 1 acid glycoprotein, high density and low density lipoprotein, IgG and alpha 1 antitrypsin were identified as effective non-specific inhibitors. Alpha-1-acid glycoprotein was confirmed to be the most potent plasma protein inhibitor. Cohn fractions were evaluated for the presence of the postulated endocoid of [3H] imipramine binding site. PMID- 3352468 TI - Calcium uptake into renal brush border membranes in vitamin B6 deficient rats. AB - The calcium uptake into renal brush border membrane vesicles, which has been purified from normal or vitamin B6 deficient rat renal cortex by calcium precipitation, was investigated. The values of Km and Vmax were determined to be 1.89 mM and 4.26 nmol of Ca2+/mg of protein per 20s in vitamin B6 deficient rats, respectively. This Vmax was lower than that of normal rats. The chemical compositions of renal brush border membranes did not display a difference in normal and vitamin B6 deficient rats. The amount of brush border membranes isolated from 1 gram of renal cortex in vitamin B6 deficient rats was less than in normal rats. PMID- 3352467 TI - Decrease in plasma tryptophan after tryptophan-free amino acid mixtures in man. AB - Male healthy subjects, fasting 12 hours, ingested increasing amounts of a mixture containing a fixed proportion of seven essential amino acids (L-isoleucine 11.5%, L-leucine 18.0%, L-lysine 13.1%, L-methionine 18.0%, L-phenylalanine 18.0%, L threonine 8.2%, L-valine 13.1%) and lacking tryptophan. The diets produced a rapid fall in plasma tryptophan which was proportional to the total amount of the amino acids ingested. Following the highest dose administered (36.6 g) plasma tryptophan fell to a minimum of about 35% the initial level and remained markedly reduced at 6 hours after treatment. The mechanism of this decrease and its potential clinical relevance are discussed. PMID- 3352469 TI - Neutral lipid transfer protein does not regulate alpha-tocopherol transfer between human plasma lipoproteins. AB - Vitamin E has no known plasma carrier protein and is transported by plasma lipoproteins. The site of association of vitamin E in the lipoprotein particle and the mode of transfer of vitamin E between plasma lipoproteins have not been ascertained. Since neutral lipids (triglycerides and cholesterol esters) exchange between plasma lipoproteins by processes mediated by neutral lipid transfer protein, we questioned that if vitamin E, a hydrophobic molecule, is carried in the core of the lipoprotein particle then its transfer between plasma lipoproteins may be mediated by neutral lipid transfer protein. Transfer of D alpha(5-methyl-3H)tocopherol from in vitro-labeled human plasma lipoprotein fractions to other plasma lipoproteins was measured under incubation conditions that were designed to yield markedly differing degrees of neutral lipid exchange. Despite the presence of the d greater than 1.21 g/ml lipoprotein-poor plasma fraction or purified lipid transfer protein that resulted in up to a 10-fold increase in neutral lipid transfer, vitamin E transfer between very low density lipoproteins, low density and high density lipoproteins remained constant. Even excess amounts of lipid transfer protein, which caused triglyceride transfer between very low density and high density lipoproteins to reach saturation, failed to affect significantly vitamin E transfer. Vitamin E distribution between lipoprotein fractions did correlated with lipoprotein mass ratios. Vitamin E transfer was higher as the protein ratio of acceptor lipoproteins to donor lipoproteins increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352470 TI - Lysophosphatidylcholine accumulation in the ischemic canine heart. AB - The production of cardiac arrhythmias and the elevation of lysophosphatidylcholine level in the ischemic myocardium have been well documented in a number of studies. However, the relationship between the production arrhythmias and the elevation of tissue lysophosphatidylcholine level was not reported. In this study, the lysophosphatidylcholine level and the occurrence of cardiac arrhythmias in the ischemic canine heart were monitored. A temporal relationship between the accumulation of lysophosphatidylcholine and the occurrence of arrhythmias was established after five hr of ischemia. A significant elevation of lysophosphatidylcholine was detected at three hr of ischemia without the occurrence of arrhythmias. The results indicate that cardiac arrhythmias did not cause the elevation of lysophosphatidylcholine and if lysophospholipids are causally related to the arrhythmias that a critical level of the lysophospholipid must accumulate in order to elicit electrophysiological alterations. PMID- 3352471 TI - Metabolism of sitosteryl beta-D-glucoside and its nutritional effects in rats. AB - [4-14C]Sitosteryl beta-D-glucoside, intragastrically administered to rats, was not absorbed by the intestinal mucosa. At three hr after the application, radioactivity was concentrated almost exclusively in the digesta of stomach, small intestine as well as cecum and colon, whereas only low proportions of radioactively labeled compounds were found in the various tissues of the gastrointestinal tract. Minor proportions of labeled metabolites of [4 14C]sitosteryl beta-D-glucoside, such as sitosterol and sitosteryl esters, were formed in the small intestine in vivo and in slices of small intestine in vitro. In the tissues of cecum and colon as well as the digesta derived from them, high proportions of labeled coprositostanol, i.e. 24 alpha-ethyl-5 beta-cholestan-3 beta-ol, that obviously had been formed by bacterial degradation of the substrate were detected. The feeding of sitosteryl beta-D-glucoside (0.5 g/kg body weight X day) over a period of four weeks did not alter significantly body weights or organ weights of rats. Analyses of steryl lipids of the various organs and tissues confirmed the findings obtained with the radioactive substrate: neither sitosteryl beta-D-glucoside nor sitosterol or sitosteryl esters derived therefrom had been transported in appreciable amounts to organs and tissues outside the alimentary canal during the feeding period. Minor proportions of unmetabolized sitosteryl beta-D-glucoside were detected in the tissues of stomach and intestine, whereas large proportions of the substrate were found in feces of rats that had received the sitosteryl beta-D-glucoside-containing diet; coprositostanol was found in feces of these animals in high proportions as well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352472 TI - Genetic variations in serum lipid levels of inbred mice and response to hypercholesterolemic diet. AB - The serum lipid contents of a number of inbred and congenic strains of mice were measured. There were inter-strain variations in each of the lipid fractions in mice fed a normal diet. Male and female C3H mice had the highest total cholesterol level; AKR mice showed the lowest values. Serum phospholipids were correlated well with cholesterolemia. The greatest variations between strains were in the triglyceride levels. There also was significant variation in the high density lipoprotein cholesterol serum levels (from 73-88% of the total cholesterol). The response to a hypercholesterolemic diet (1% cholesterol) was tested in seven inbred strains. All strains showed changes in serum cholesterol and in the proportions of the lipoproteins fractions. There was a large increase in the low density lipoprotein + very low density lipoprotein fractions. Feeding the diet revealed marked interstrain differences in the responses of the serum cholesterol and electrophoretic lipoprotein profiles. The C57BL/6 and B10.D2 strains were hyperresponders to the hypercholesterolemic diet with 71% and 63% of their serum cholesterol in the low density lipoprotein plus very low density lipoprotein fractions, respectively. PMID- 3352473 TI - Subcellular distribution of disaturated phosphatidylcholine in developing rabbit lung. AB - To determine the subcellular distribution of disaturated phosphatidylcholine (DSPC) in lung tissue during perinatal development, fetal rabbits at 24, 26, 28 and 31 (term) days gestation and newborns were studied. Following alveolar lavage, fractions enriched in nuclei-cellular debris, mitochondria, microsomes, surfactant (lamellar bodies) and cytosol were prepared from the residual tissue homogenate, and their DSPC content was determined. The DSPC content of the unfractionated residual lung tissue homogenate progressively and significantly increased during fetal development, rising from 9.09 +/- 0.91 to 17.45 +/- 2.88 mg/g dry lung between 24 days gestation, and term. Between 24 and 26 days gestation the overall increase in tissue DSPC was due to a two-fold increase in the mitochondrial, microsomal and cytosolic pools. Lamellar bodies were first isolable at 26 days gestation. The DSPC content of this fraction increased six fold (from 0.10 +/- 0.02 to 0.67 +/- 0.15 mg/g dry lung) between 26 and 28 days gestation and a further seven-fold (to 4.63 +/- 1.06 mg/g dry lung) by term, accounting for the overall increase in the tissue homogenate value during this time period. By the first postnatal day, microsomal and cytosolic DSPC increased another two-fold, but no significant change occurred in the other subcellular fractions. Alveolar lavage DSPC progressively increased over the time period studied. While there was no change in the lamellar body DSPC/total PC ratio during fetal development, each of the mitochondrial, microsomal and cytosolic ratios decreased between days 26 and 28 of gestation and then increased at term.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352474 TI - Differential utilization of long chain fatty acids during triacylglycerol depletion. I. Rat heart after ischemic perfusion. AB - Rat hearts were perfused with Krebs-Henseleit buffer for 90 min according to the Langendorff procedure. Normoxic perfusion for 90 min resulted in minor changes in fatty acid composition and a decrease in residual heart triacylglycerol to 60% of preperfusion values. When the protocol included 30 min of slow perfusion-induced ischemia, the hearts were observed to be depleted of 89% of their initial triacylglycerol content. The triacylglycerol fatty acid composition (mg %) remained similar after compared to before perfusion except for a 121 mg % increase in stearic acid and a 225 mg % increase in arachidonic acid. The percentage composition of both fatty acids was significantly inversely correlated with the amount of triacylglycerol remaining in the heart after perfusion. Postperfusion, arachidonic acid and stearic acids were present at nearly 1:1 in the residual heart triacylglycerol, suggesting that a common mechanism may be involved in the selective retention of these fatty acids by the heart. PMID- 3352475 TI - Fluorescence formation from hydroperoxide of phosphatidylcholine with amino compound. AB - The hydroperoxides of methyl linoleate, 1-palmitoyl-2-linoleoyl phosphatidylcholine and trilinolein each produced similar fluorescent substances through reaction with amino compounds after decomposition by heme methyl ester. Fluorescent substances formed from methyl linoleate with 1-aminopentane revealed characteristic fluorescence peaks on HPLC, while those obtained from 1-palmitoyl 2-linoleoyl-phosphatidylcholine and trilinolein were not eluted under the same conditions. However, when both of these fluorescent substances were transesterified to methyl ester, the same fluorescence peaks were observed. This result suggests that fluorescent substances formed from oxidized membrane lipids with amino compounds remain attached to phospholipids without being released from their glycerol backbone. PMID- 3352477 TI - Effects of thermal denaturation on the longitudinal relaxation time (T1) of water protons in protein solutions: study of the factors determining the T1 of water protons. AB - The factors determining the longitudinal relaxation time (T1) of water protons in protein solutions were investigated by analyzing the effects of thermal denaturation on the T1 of the water protons. We treated the water protons and the protein protons "on a protein surface" as a dipole-dipole coupled two-spin system where relative translational diffusion is the dominant mechanism, and measured the change in the time development of the nuclear Overhauser effect (NOE) factors of the water protons. The T1 of the water protons was shortened markedly when the proteins were thermally denatured. Our analysis indicates that this relaxation enhancement is due to an increase in the value of the translational correlation time as well as the fraction of hydration water molecules, though the influence of "proton exchange" between the water protons and the labile protein protons cannot be completely neglected. PMID- 3352476 TI - Effects of dietary peanut oil on serum lipoprotein patterns of rats. AB - Oils prepared from two varieties of peanuts and from a hybrid corn having linoleic acid concentrations substantially different from the respective commercial oils were compared with commercial oils for their effects on serum lipids of weanling female rats. In the first experiment, serum lipid patterns appeared to reflect linoleic acid content of the dietary oil. However, with a longer feeding period in the second experiment, serum lipid patterns were determined by the plant source of the dietary oil rather than its linoleic acid content; all peanut oils differed from both corn oils in their physiological effects. Diets containing triglyceride, hydrocarbon and sterol fractions obtained by liquid chromatography of peanut and corn oils were fed to female rats. The data provide no evidence that the hydrocarbon or sterol fractions of peanut oil are responsible for its unusual atherogenicity when fed as the sole fat source or that similar fractions from corn oil are protective against the effects of peanut oil. PMID- 3352479 TI - Precision in calculated rho, T1 and T2 images as a function of data analysis method. AB - In NMR imaging rho, T1 and T2 images are usually calculated from a set of partial saturation, saturation recovery or inversion recovery experiments with multiple echoes and multiple repetition times. Several methods can be envisaged to extract parameter images from such a set of source images. These methods to a greater or lesser extent take advantage of the fact that a multiple echo/multiple repetition time experiment provides a set of largely independent T1 and T2 measurements. In this study several data analysis methods, including weighted and non-weighted averaging of results of independent T1 and T2 measurements, weighted and non weighted averaging of source images prior to data reduction and simultaneous three-parameter fitting, were compared against another in terms of precision, computational efficiency and robustness. The predicted performance of the examined methods was verified by stochastic simulation experiments. PMID- 3352478 TI - Application of the maximum likelihood principle to separate exponential terms in T2 relaxation of nuclear magnetic resonance. AB - The method of maximum likelihood has been implemented for the estimation of multiple exponential components of T2 decay curves in spin echo NMR measurements on biologic tissues. Each Each component contributes an exponential term described by two parameters (initial amplitude and T2) to the T2 decay curve. The maximum likelihood method estimates the parameters and their standard errors for all terms simultaneously, avoiding the subjectivity inherent in methods such as graphical peeling. In the model used, it was assumed that water protons are compartmentalized and that the measured spin echo signals from the protons undergoing relaxation obey the Poisson distribution. A system of non-linear equations was derived and solved iteratively for the values of the exponential parameters which maximize the likelihood of obtaining the observed data under these assumptions. The approach was implemented for bi- and tri-exponential models on a MicroVAX II computer (Digital Equipment Corporation, Maynard, MA). Simulations of bi- and tri-exponential data, with and without system noise, were analyzed to assess the accuracy and reproducibility of the method. A subset of the simulations was repeated with non-linear least squares techniques and was compared to the results obtained with maximum likelihood. Rabbit muscle and gerbil brain samples were measured and analyzed with the maximum likelihood method. The simulations showed that within specific limits on relative sizes and relaxation rates of components, these parameters can be estimated with errors less than 5%. The comparison to non-linear least squares analysis showed that the maximum likelihood method is generally superior in estimating the parameters in difficult cases. The results from tissue measurements demonstrate that the method is effective even in cases where graphical peeling would clearly not yield reliable results. PMID- 3352480 TI - Proton MR properties of lyophilized urine samples from normal and stone former individuals. AB - Proton MR measurements were performed in lyophilized urine samples collected from 5 normals (N) and 5 idiopathic hypercalciuric recurrent stone formers (SF). T1 and T2 relaxation times were measured with a Bruker PC Multispec at 20 MHz and 37 degrees C in the lyophilized samples and in samples gradually rehydrated. Significantly (p less than 0.01) prolonged T1 and T2 relaxation times were measured after addition of water to the lyophilized samples. The relaxation time prolongation patterns were significantly different (p less than 0.01) for the two groups; the rehydration curves of the lyophilized urine samples from the SF group had relatively shorter lag than that of N group. In calculations of water compartmentalization for similar water content, significant (p less than 0.01) differences in the fraction of bound water (FB) were found between the two groups. These results may reflect differences in the macromolecular properties, contents, in the amount of water binding sites and/or in the water multilayer thickness between the two groups. These differences, expressed as changes of the relaxation times values may provide new diagnostic possibilities of different renal pathologies. PMID- 3352481 TI - Errors in T1-determination using multislice technique and Gaussian slice profiles. AB - Multislice SE- or IR-sequences with different TR- and T1-times, respectively, are often used, to determine T1- and T2-values for tissue characterisation. To investigate the perturbating influence of the sequential excitation in multislice technique, we measured the signal intensities and calculated the T1-values of phantoms as a function of gap widths between neighboured slices. Phantoms contained fluids of different T1. We found a strong dependence of signal intensities and therefore of calculated T1-values on the gap width, when a T1/TR ratio of more than 0.3-0.4 was reached. T1-values are considerably overestimated in this case, whereas T2-values are not influenced by the sequential excitation. We conclude that reliable T1-measurements necessitate a large spacing of more than 1 slice thickness between adjacent slices. PMID- 3352482 TI - Rapid 19F magnetic resonance imaging of perfluorooctyl bromide in vivo. PMID- 3352483 TI - MRI of the head and neck. PMID- 3352484 TI - Electrocardiographic gating and monitoring in NMR imaging. AB - ECG gating and monitoring during NMR imaging may be achieved reliably by applying the principles in this tutorial. In order to use the ECG signal both for triggering and for patient monitoring it must have a prominent R-wave, while at the same time must have little artifact from gradient switches or the Lorentz voltage across the aorta, and not be significantly distorted by gradient switching artifacts. The twin goals of no image artifacts and minimal ECG artifacts may be achieved by the following means: (1) using ECG electrodes with minimal metal, (2) selecting electrodes and cables with no ferrous metals, (3) placing the limb electrodes close together, (4) placing the line between the limb electrodes and the leg electrode parallel to the magnetic flux lines and, if possible, parallel to the transverse component of the gradient flux lines, (5) keeping the area between the limb electrodes and the leg electrode small, (6) placing that area in the center of the imager and (7) twisting or braiding the cables. Following these principles allows artifact-free images and reliable ECG monitoring during ECG-gated NMR imaging examinations. PMID- 3352486 TI - The difference between in vitro and perfused organs. PMID- 3352485 TI - MR imaging of liver abscesses; application of Gd-DTPA. AB - The potential utility of Gd-DTPA contrast enhancement of MR images in the evaluation of liver abscesses was assessed in rodents. Twelve rats with surgically implanted sterile liver abscesses were imaged at various stages of focal hepatic inflammation, 48 hours, 4 days, 7 days, 14 days and 21 days after lesion induction. Spin echo images, acquired before and repeatedly after intravenous injection of 0.2 mmol/kg Gd-DTPA, demonstrated improvement of the lesion-to-background contrast ranging from 2% to 40% depending on the stage of the disease. The enhancement pattern also varied with abscess evolution. Two, four and seven-day-old abscesses typically showed a ring enhancement, whereas two and three-week-old abscesses presented largely homogeneously enhancing lesions. In the earlier lesions, contrast enhanced rim surrounding the low intensity center corresponded histologically to the formation of a capsule consisting of fibrous tissue and inflammatory cells. The center was necrotic. Data show that abscesses can be detected on images acquired with long repetition and echo times without injection of Gd-DTPA. The administration of Gd-DTPA, however, improved the lesion-to-background contrast and helped to define the abscess capsule evolution. PMID- 3352487 TI - [Improved method of equilibrium radionuclide ventriculography]. AB - The commonly used method of static radionuclide ventriculography with a cardiosynchronizer does not permit obtaining a curve of ventricular function over a complete cardiac cycle, especially using computers with a small memory volume. Besides, the final segment of a curve is usually insignificant as a result of variations in a duration of the R-R interval. A method of 2-stage recording of radionuclide ventriculography has been proposed, the second stage being shifted to a certain time interval, i. e. a delay line is introduced between a synchronizing device and computer. Two methods of delay--in the software and hardware--are proposed, the latter being more preferable as it makes unnecessary extra technical devices. Particular attention is drawn to a choice of delay time depending on a computer memory volume: in a small memory volume delay time must be approximately one-third of the patient's R-R interval. PMID- 3352488 TI - [Experimental perfusion scintigraphy of the myocardium using 199Tl chloride]. AB - The authors conducted phantom, pharmacokinetic and scintigraphic investigation of the radionuclide thallium-199. It was shown that the spectrum of x-rays permitted good imaging of the phantom on photon energy peaks of 72 keV using a scintillation camera with a standard high resolution collimator. The physiochemical and pharmacokinetic characteristics of the radionuclide give an opportunity to use it for perfusion scintigraphy of the myocardium. PMID- 3352489 TI - [Structure of functional scintigraphic images during the development of gallbladder bile reflux into the intrahepatic ducts]. AB - The authors proposed a method of cholescintigraphy with functional imaging reflecting RP distribution within the entire area in the field of vision of a gamma-chamber detector taking account of the type of motor activity of the gall bladder. This method was based on plotting an activity-time curve along the outer contour of a gall bladder image, the determination of moments of change in gall bladder motor activity on this curve, and the calculation of corresponding gradients of RP accumulation and clearance functions represented on an image where the color of each element was determined by a sign of the gradient and its intensity--by its absolute value. The use of this method in 92 patients made it possible to reveal conditions with possible B-bile reflux into the intrahepatic ducts, and to raise its diagnostic accuracy by 7% as compared to a routine analysis of activity-time curves by decreasing the number of false-negative results. PMID- 3352490 TI - [Localization of left ventricular myocardial lesions using 201Tl chloride scintigrams]. AB - The authors propose some methodological approaches including stereometric methods, for determination of visible left ventricular walls in different projections of a gamma-chamber detector with relation to a position of the left ventricular anatomical axis (LVAA) in space to improve topographic diagnosis of left ventricular myocardial lesions with 201Tl. The above method can be implemented on computer. PMID- 3352491 TI - [Repeated irradiation of patients with Hodgkin's disease in connection with local recurrences]. PMID- 3352492 TI - [Topometric and clinico-dosimetric aspects of the radiotherapy of cancer of the oropharynx]. AB - The use of modern diagnostic facilities led to a study of the physico-dosimetric, topometric and clinical aspects of radiotherapy of oropharyngeal cancer. The most effective approaches to therapy of oropharyngeal tumors with account of their site, spread and degrees of differentiation were developed. The most effective method was shown to be the combination of gamma-beam therapy (50 Gy) with electron-photon radiation (20 Gy) of an accelerator of 18-20 MeV, radiation exposure of normal tissues being lowered by approximately 10-20% as compared to that in gamma-beam therapy used alone. The use of the above method in 45 oropharyngeal cancer patients resulted in an immediate clinical effect (disappearance of a tumor and regional metastases (if any) in 60% of the patients. The 2-year survival rate calculated by actuarial curves, was 62 +/- 10%. PMID- 3352494 TI - [Increasing the efficacy of radiation damage to transplantable tumors using postradiation hypoxia]. AB - It was shown that the duration of remission (by the criterion of the time of reaching an initial tumor size) of ascitic solid Ehrlich carcinoma of mice could be doubled by post-radiation tourniquet hypoxia both in single and fractionated irradiation. The effect of placing a tourniquet is equal to a 1.5-fold dose increase. PMID- 3352493 TI - [Radiation-induced changes in normal tissues during neutron-photon therapy of recurrent cancer of the root of the tongue]. AB - The paper is concerned with a case of a 2-year follow-up of a patient with recurrent cancer of the root of the tongue treated with fast neutrons on the Y 120 cyclotron. Medical history included a preoperative course of photon therapy at a dose of 40 Gy and operation. The total focal dose of fast neutrons of a repeated irradiation course was 11.2 Gy, that of photons--14 Gy corresponding to a total photon equivalent dose of 50 Gy. The authors provided the evidence of late radiation changes of the skin, temporomandibular articulation, pharynx, and the upper esophagus, and analyzed the causes of development of radiation complications. PMID- 3352495 TI - [Fractionated irradiation of Ehrlich carcinoma using fast neutrons]. AB - Ehrlich's carcinoma growth inhibition was studied under the conditions of fractionated irradiation with fast neutrons and x-rays. Fast neutrons were obtained from a reaction of 13.6 MeV alpha----Be on the Y-120 cyclotron. Neutron beam irradiation doses were within 2-17 Gy, x-ray doses from 7.5 to 72 Gy. Tumors were subjected to local irradiation with 1-8 fractions at a 3-4 day interval. The results showed that an increase in the total duration of a course of irradiation and a decrease in a dose per fraction resulted in a reduced effect of carcinoma growth inhibition. At the same time, an increase in the fast neutron RBE under these conditions from 3.4 (in single irradiation) to 5.4 (in 8-fold irradiation) indicated more pronounced inhibition of reparation and/or repopulation in a tumor in neutron beam irradiation. PMID- 3352496 TI - [Calculation of doses and choice of regimen in x-ray contrast studies of the urinary tract in children]. PMID- 3352498 TI - [Quality control in radionuclide diagnosis (principles and approaches)]. PMID- 3352497 TI - [Biological effects of the intramuscular administration of 239Pu as affected by chelate therapy]. PMID- 3352499 TI - 1988 American College of Sports Medicine. Annual meeting abstracts. May 25-28, Dallas, Texas. PMID- 3352500 TI - A versatile multinuclear probe designed for in vivo NMR spectroscopy: applications to subcutaneous human tumors in mice. AB - We describe a versatile NMR probe that is designed for a variety of in vivo spectroscopic studies on small animals in vertical wide-bore magnets. Replaceable brackets enable the coils to be exchanged readily in order to observe 1H, 13C, 31P, and other nuclei, and to carry out double-resonance experiments. Two solenoidal coil designs are described and applied to observe 31P, 13C, and 1H natural abundance spectra of subcutaneously implanted human tumors in mice. For 31P and 31C observation with 1H decoupling, a concentric coil arrangement was employed with a broadband inner coil and the outer coil tuned to 1H at 400 MHz. A single coil tuned to 400 MHz was used to observe 1H resonances. A thin copper foil design was found to be superior with respect to S/N and resolution to previously described Faraday shields used to shield the NMR signals originating from nontumor tissues. 31P spectra of in vivo tumor tissue were compared to spectra of in vitro perfused tumor cells of the same origin. Tumor tissue in vivo exhibited much higher levels of inorganic phosphate and phosphocreatine. Signals from [13C2]glucose and its major metabolite, [13C2]lactate, were readily observed and monitored in an unobstructed region of the 13C spectra of tumor tissue in vivo following the injection of [13C2]glucose in adjacent tissues. A 1H spectrum of tumor tissue, characterized by five broad resonances, was observed with excellent water suppression. PMID- 3352501 TI - Multiline chemical-shift (MULCH) imaging. AB - A fast chemical-shift imaging technique is presented. The method involves saturating all spins outside a plane, selectively exciting individual lines, phase encoding along each line, sampling the FID without gradients, and interleaving interrogation of multiple lines. A 64 X 64 array of spectra with 5 Hz resolution can be obtained in 17 min. PMID- 3352502 TI - Triple nuclear NMR studies of cerebral metabolism during generalized seizure. AB - Noninvasive NMR spectroscopy of 1H, 31P, and 23Na is performed simultaneously to study brain metabolism during grand mal seizures. Decreases in PCr and increases in lactate associated with seizure as well as an intracellular shift of the Na+ ion pool are demonstrated. A close correlation between the phosphate potential and the intensity of the seizure, as well as the intra/extracellular ionic gradient, is shown. PMID- 3352503 TI - Continuous distributions of NMR relaxation times applied to tumors before and after therapy with X-rays and cyclophosphamide. AB - In vivo measurements of T1 and T2 values in two experimental tumors growing in the legs of mice were made during tumor growth and after treatment of the tumor with either X-rays or cyclophosphamide. The T1 and T2 values were obtained by fitting the data to continuous distributions of relaxation times. This technique gives broad distributions of relaxation times which are characterized by a number of peaks with characteristic T1 and T2 values. Before treatment, the T1 and T2 values increased before a palpable tumor mass could be detected. The response to subcurative doses of either treatment method was a reduction in the T1 and T2 values and a parallel reduction in tumor weight. Although local recurrence was characterized by the same pattern of tumor growth as was observed before treatment, therapy was found to give higher relaxation time values than those measured in untreated tumors. The higher relaxation time values of tumor-bearing legs were the result of redistribution of the peaks in the distribution and not changes in the relaxation times of the individual peaks. PMID- 3352504 TI - 31P NMR characterization of graded traumatic brain injury in rats. AB - Irreversible tissue injury following central nervous system trauma is believed to result from both mechanical disruption at the time of primary insult, and more delayed "autodestructive" processes. These delayed events are associated with various biochemical changes, including alterations in phosphate energy metabolism and intracellular pH. Using 31P NMR, we have monitored the changes in phosphorus energy metabolism and intracellular pH in a single hemisphere of the rat brain over an 8-h period following graded, traumatic, fluid percussion-induced brain injury. Following trauma the ratio of phosphocreatine to inorganic phosphate (PCr/Pi) declined in each injury group. This decline was transitory with low injury (1.0 +/- 0.5 atm), biphasic with moderate (2.1 +/- 0.4 atm) and high (3.9 +/- 0.9 atm) injury, and sustained following severe injury (5.9 +/- 0.7 atm). The initial PCr/Pi decline in the moderate and high injury groups was associated with intracellular acidosis; however, the second decline occurred in the absence of any pH changes. Alterations in ATP occurred only in severely injured animals and such changes were associated with marked acidosis and 100% mortality rate. After 4h, the posttraumatic PCr/Pi ratio correlated linearly with the severity of injury. We suggest that a reduced posttraumatic PCr/Pi ratio may be indicative of altered mitochondrial energy production and may predict a reduced capacity of the cell to recover from traumatic injury. PMID- 3352505 TI - Some observations of the design of rf coils for human internal use. AB - Some features of the design and implementation of NMR probes for insertion into peripheral orifices of the body are described. In particular, the possibilities of using parasitic coils without direct connections in conjunction with conventional whole body coils are examined. The use of windings around the NMR probe carrying gradient pulses as a means of eliminating the very high signals from tissue immediately adjacent to the coil windings is also evaluated. These approaches are, in practice, difficult to combine, and hence need to be viewed almost as alternative possibilities. Practical results of experimental investigations are presented using both phantoms and volunteers. PMID- 3352506 TI - Experimental acute pancreatitis: MR relaxation time studies using gadolinium DTPA. AB - Spin-lattice (T1) and spin-spin (T2) relaxation times of normal and sodium taurocholate-induced pancreatitis (38 rats) were determined in vitro using a 10.7 MHz magnetic resonance (MR) spectrometer. The increase in pancreatic T1 time in acute hemorrhagic pancreatitis correlated well with the elevated water content of the organ. Gadolinium-DTPA did not affect significantly the relaxation times of normal pancreas in vitro during 1 t 20 min postinjection, but it decreased the elevated T1 times of inflamed pancreas almost to baseline values. MR imaging studies of rat pancreas in vivo (8 rats, 0.35-T resistive magnet) indicated that the swollen pancreas and associated edema were depicted using a T2-weighted SE sequence. Fifteen minutes postinjection of gadolinium-DTPA a homogeneous enhancement of inflamed pancreas was detected. The differentiation of pancreatic necrotic foci from surrounding viable tissue and edema could not be detected on Gd-DTPA-enhanced MR images after 15 min postinjection although microscopical workup indicated these different tissue constituents in the pancreas. PMID- 3352507 TI - Acquisition order and motional artifact reduction in spin warp images. AB - Multiple averaging can be a powerful tool against motional artifacts if significant motion occurs between the redundant acquisitions taken at a given gradient strength. However, if the time delay between these redundant measurements is too short, data or images depicting the patient is exactly the same position will be combined. Pooling such identical data has no effect on motional artifacts. This problem can be solved by increasing TR, increasing the number of redundant acquisitions, or changing the order in which acquisitions are taken. Usually all acquisitions at a particular value of the warp gradient are taken before proceeding to the next gradient value. This order minimizes motion between redundant acquisitions and so maximizes artifacts. The effect of other acquisition orders on both periodic and nonrepetitive motion is discussed. Human images for breathing and phantom results for single-occurrence motions are presented. PMID- 3352508 TI - Noninvasive measurement of molar concentrations of 31P metabolites in vivo, using surface coil NMR spectroscopy. AB - The measurement of absolute concentration of 31P metabolites is described, using water 1H as an internal concentration standard. An analysis of the effect of variations in coil Q on flip angle and sensitivity is presented and verified experimentally. Concentrations of nucleoside triphosphate in rat brain and muscle have been measured. PMID- 3352509 TI - Fast MRI data acquisition using multiple detectors. AB - We present a novel imaging procedure using multiple receiver coils. This circumvents the sequential acquisition of signals required by conventional imaging strategies. The advantage of this technique over existing subsecond imaging techniques is that (a) contrast can be maintained and (b) there is no magnetic field gradient switching involved. PMID- 3352510 TI - Accurate quantification of in vivo 31P NMR signals using the variable projection method and prior knowledge. AB - Free induction decay signals are analyzed by fitting a model function directly in the time domain. No starting values are needed for linear model parameters, and omission of corrupted data points poses no problems. A significant gain of accuracy is achieved by imposing prior knowledge about the model parameters. PMID- 3352511 TI - Opsoclonus, myoclonus, ataxia, and encephalopathy in adults with cancer: a distinct paraneoplastic syndrome. AB - The clinical and pathological findings in 4 adults with cancer and opsoclonus were compared with those of 15 other patients described elsewhere. The clinical syndrome of paraneoplastic opsoclonus is characterized by the acute onset of opsoclonus and truncal ataxia, often accompanied by encephalopathy, myoclonus and a cerebrospinal fluid pleocytosis. Unlike most other paraneoplastic syndromes, the course is often remitting and relapsing. Neuropathological examination in 3 of our patients showed lymphocytic cuffing of occasional blood vessels throughout the central nervous system, associated with a mild, diffuse proliferation of microglia in 1 patient. Apart from a mild, patchy loss of Purkinje cells in 1 patient, there was no loss of neurons from the cerebellum, brainstem, cerebral hemispheres, or spinal cord. These patients differ from those with the more common paraneoplastic cerebellar degeneration by the predominance of truncal over limb ataxia, the presence of myoclonus, the absence of severe dysarthria, a tendency for remission, and the preservation of Purkinje cells. PMID- 3352513 TI - Perinephric abscess. Modern diagnosis and treatment in 47 cases. AB - The records of 47 patients with a perinephric abscess diagnosed from 1975 to 1986 at 8 San Francisco Bay Area hospitals were reviewed. The mean age was 51 years. Fifty-five percent were females and 45%, males. The left kidney was affected in 47% of cases, the right kidney in 40%, both in 4%, and a transplanted pelvic kidney in 9%. Fever (55%), chills or diaphoresis (47%), flank pain (40%), abdominal pain (40%), and nausea or vomiting (32%) were the most common presenting symptoms. About half the patients had symptoms for 1 week or less and 12% had no symptoms. Fever was documented before diagnosis in 88% of patients. Abdominal mass (13%) or tenderness (49%), and flank mass (9%) or tenderness (42%) were seen less frequently, and 11% of patients did not have fever, flank, or abdominal findings. The most frequent underlying conditions included previous urologic surgery (45%), previous urinary tract infection (38%), diabetes mellitus (36%), and urinary tract stones (36%). Cultures of perinephric abscesses yielded gram-negative aerobes in 52% of patients, primarily Escherichia coli. Staphylococcus aureus was isolated in 26% of patients and anaerobes in 17%. A single pathogen was isolated in 71% and multiple isolates in 29%. Of interest and great potential therapeutic importance was culture of anaerobes, primarily Bacteroides spp. in 17%, Enterococcus spp. in 7%, and Candida albicans in 7%. Positive blood and urine cultures identified perinephric abscess organisms exactly in 58% and 37% of cases, respectively. Routine laboratory tests such as the white blood cell count and urinalysis were insensitive and non-specific for perinephric abscess. Leukocytosis and anemia at admission were seen in slightly more than half of the patients. For radiologic diagnosis, computerized tomographic scanning was most helpful. Ultrasound and intravenous pyelography were falsely negative in about one-third of cases. Mortality (13%) was low in this series when compared with earlier studies, and probably reflects modern medical care. Six patients (13%) died during hospitalization, 2 of whom had diagnosis of PNA established only at autopsy. Drainage of the perinephric abscess was carried out by open surgical drainage in 64% of patients, percutaneous drainage in 19%, and both in 13%. The initial procedure, whether open surgical drainage or percutaneous catheter drainage, was usually successful. Late complications included nephrocutaneous fistulas in 3 patients and disseminated candidiasis in 1 patient. PMID- 3352512 TI - Enzymatic diagnosis in non-spherocytic hemolytic anemia. AB - Blood samples from 722 unrelated patients with anemia and/or reticulocytosis were submitted to our laboratory for red cell enzyme assay during the past 7 years. Among these 722 cases, we found 82 cases of 7 different red cell enzyme deficiencies and 2 of unstable hemoglobin. Abnormalities of pyruvate kinase (PK) were found to cause hemolysis in 55 patients. Although their average PK activity was about 35% of the normal level, 5 showed normal and 2 demonstrated high PK activity. Among 17 patients in whom pyruvate kinase assays or screening tests had been carried out in routine laboratories, the correct diagnoses had been made in only 4. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was found in 15 patients, pyrimidine 5'-nucleotidase deficiency in 5, glucose phosphate isomerase deficiency in 3, adenylate kinase deficiency in 2, phosphoglycerate kinase deficiency in 1, and glutathione synthetase deficiency in 1 patient. Even after we performed a panel of over 20 different red cell enzyme assays, 519 patients still remained undiagnosed. PMID- 3352514 TI - The emerging role of Fusarium infections in patients with cancer. AB - Infection due to Fusarium species is an increasing cause of serious potentially fatal disease in patients with cancer. We described 9 patients with infection caused by Fusarium species during a 4-year period at the M. D. Anderson Hospital. The spectrum of infections included disseminated disease in 4 patients, skin or soft-tissue infections in 3, pneumonia in 1, and fungemia in 1. All 4 patients with disseminated infection had culture- and biopsy-proven skin lesions caused by Fusarium species and the blood cultures yielded the organism in 3 of these 4 patients. Maxillary sinusitis was the presenting manifestation of Fusarium infection in 2 of these 4 patients, suggesting that paranasal sinuses are potential portals of entry for the infection. Eight patients had a hematological malignancy and 7 were neutropenic at the onset of their infection. Patients with deep-seated infections remained neutropenic and died from infection despite treatment with amphotericin B. All 5 isolates tested in vitro showed resistance to ketoconazole and miconazole, whereas 3 were susceptible to amphotericin B. Fusarium species could play a role in producing myelosuppression and fungal cultures are required to differentiate it from the more commonly encountered Aspergillus species. Fusarium species are emerging as a serious, potentially fatal, pathogen in patients with cancer. PMID- 3352515 TI - Mood and memory: mood-congruity effects in absence of mood. PMID- 3352516 TI - Exploring long-term modality effects: vocalization leads to best retention. PMID- 3352517 TI - Visual working memory in young children. PMID- 3352518 TI - Memory confusions for real and imagined completions of symmetrical visual patterns. PMID- 3352520 TI - Focused search of semantic cases in question answering. PMID- 3352521 TI - The crossword puzzle paradigm: the effectiveness of different word fragments as cues for the retrieval of words. PMID- 3352522 TI - Memory access: the effects of fact-oriented versus problem-oriented acquisition. PMID- 3352519 TI - Comparison processes on visual mental images. PMID- 3352524 TI - The replacement effect: repeating some items while replacing others. PMID- 3352523 TI - Decision time, subjective probability, and task difficulty. PMID- 3352525 TI - Distribution of psychiatric beds, United States and each state, 1984. PMID- 3352526 TI - Triparental crosses in Streptomyces coelicolor A3(2) as a means of demonstrating the de-repression of SCP1 plasmid conjugative functions. AB - A conjugative plasmid free in the cytoplasm promotes recombination if it is transferred to two plasmid-less strain in triparental crosses of Streptomyces coelicolor. The recombination frequency is the same as that of biparental crosses between a plasmid-bearing and a plasmid-less strain. The "conjugative" functions of the plasmid are responsible for recombinant formation. Hyphal contact and subsequent heterokaryon formation are necessary but not sufficient steps for the recombinant process. This paper shows that the presence of a conjugative plasmid is necessary for chromosome mobilization and subsequent recombinant formation. PMID- 3352527 TI - [Gastrointestinal diseases]. PMID- 3352528 TI - [Progress in ophthalmology]. PMID- 3352529 TI - [Fat metabolism]. PMID- 3352530 TI - [New drugs, 1978 to 1987]. PMID- 3352531 TI - Drugs for tuberculosis. PMID- 3352532 TI - Clinical utility of fine needle aspiration in the diagnosis and management of neuroblastoma. AB - Eleven fine needle aspiration (FNA) biopsies were performed in five children with neuroblastoma, including one patient with peripheral neuroectodermal tumor of the thoracopulmonary region (Askin tumor). Cytologic features in conjunction with immunocytochemistry and electron microscopy on the aspirated material enabled us to make a primary diagnosis in four of the five patients and diagnose local recurrence and metastatic disease in three patients. There were no false-positive or false-negative cytologic diagnoses; therefore, diagnostic accuracy was 100%. FNA is an extremely useful technique for the primary diagnosis and management of neuroblastoma and excludes other small cell malignancies of children. The results of this study and literature review demonstrate that FNA cytology coupled with ancillary techniques of immunocytochemistry and electron microscopy is a rapid, safe, minimally invasive procedure which can aid in the diagnosis and management of patients with neuroblastoma without resorting to more aggressive diagnostic procedures in selective cases. PMID- 3352533 TI - Effectiveness of attenuated chemotherapy in myelodysplastic syndromes: a preliminary report. AB - A small group of elderly male patients received attenuated doses of daunomycin, cytosine arabinoside (Ara-C), and 6-thioguanine for treatment of myelodysplastic syndrome (MDS). Three patients had refractory anemia with excess blasts (RAEB), and two had chronic myelomonocytic leukemia (CMMoL). All five patients had developed severe transfusion requirements for platelets and red blood cells before therapy was begun. One patient developed necrosis of the cecum and expired 19 days after therapy, but the other four all showed substantial benefit from treatment. Three of those patients received multiple courses of chemotherapy which led to improvement in peripheral blood counts in each case. Duration of responses as noted by improvement in peripheral blood counts compared to pretreatment levels ranged from 1.5 to 9 months. Despite considerable improvement in peripheral blood parameters, some of the abnormal morphologic features of MDS persisted after each course of chemotherapy. These results obtained with attenuated chemotherapy schedules in a small group of patients are sufficiently encouraging to warrant an expanded phase II trial, which is under way at the University of Rochester Cancer Center. PMID- 3352535 TI - Rhabdomyosarcoma presenting with diffuse bone marrow involvement, hypercalcemia and renal failure. AB - Rhabdomyosarcoma and other small round-cell neoplasms of infancy and childhood frequently involve the bone marrow. An unusual clinical presentation of diffuse bone marrow involvement as the sole manifestation of the disease represents a difficult diagnostic challenge. We report the case of an 18-year-old boy presenting with lower back pain, sternum tenderness, anemia, thrombocytopenia, leukoerythroblastic blood film, hypercalcemia, and renal failure. No solid tumor was found. A diagnosis of rhabdomyoblastic bone marrow metastatic involvement was initially suggested by the morphological picture, and later confirmed by the ultrastructural findings. Hypercalcemia and renal failure were controlled, initially, with furosemide and calcitonin. The patient was treated with intensive chemotherapy, including vincristine, actinomycin D, cyclophosphamide, and doxorubicin. A remission was achieved, lasting 5 months until relapse. PMID- 3352534 TI - Cytogenetic evidence for involvement of erythroid and granulocyte/macrophage progenitors in an infant with monosomy 7 syndrome presenting de novo. AB - Monosomy 7 presenting as a myelodysplastic syndrome following radiation and chemotherapy has been reported to involve a stem cell capable of both erythroid and granulocyte/macrophage differentiation. To determine if monosomy 7 presenting de novo also involves a multipotential stem cell, we examined mitoses from individual colony-forming units (CFU)-GM and burst-forming units (BFU)-E colonies derived from semisolid cultures of marrow from an infant with this disorder. Direct cytogenetic analysis of bone marrow cells disclosed the characteristic 45,XY,-7 karyotype in 32 of 35 abnormal metaphases. Metaphases were obtained from 63 (73%) of 85 CFU-GM and BFU-E colonies (median metaphases per colony = 4, range = 1-21), with well-banded analyzable chromosome spreads available for 15 of the colonies with metaphases. The monosomy 7 karyotype was present in all 14 metaphases from ten BFU-E colonies and in all seven metaphases from five CFU-GM colonies. These results indicate that the monosomy 7 karyotype can originate in haematopoietic stem cells with both erythroid and granulocyte/macrophage differentiative potential. PMID- 3352536 TI - Clinical and pathological evolution of alpha chain disease to immunoblastic lymphoma and response to COMP chemotherapy. AB - A small adolescent with alpha heavy chain disease presenting as malabsorption and evolving to immunoblastic lymphoma is reported. The pathological evolution is documented by serial endoscopy and small intestinal biopsy. Clinical and pathological remission was obtained by the use of COMP combination chemotherapy. PMID- 3352537 TI - Tumors of the thymus. PMID- 3352538 TI - Prognostic factors in 281 children with nonmetastatic rhabdomyosarcoma (RMS) at diagnosis. AB - Pretreatment characteristics of 281 children with nonmetastatic rhabdomyosarcoma, included in the registry of the International Society of Pediatric Oncology (SIOP) between January 1975 and December 1983, were examined to study the children's prognosis. The multivariate statistical method (Cox regression model) was used for each of two endpoints: survival time and disease-free time. The three most important predictors for survival time were primary site (p less than .001), clinical stage (p = .009), and sex (p = .020). The best results involved paratesticular and orbital primary sites, regardless of the clinical stage; males fared slightly better than females. These same three factors were also significant predictors for disease-free time. PMID- 3352539 TI - Trends in the incidence of childhood and adolescent cancer in Connecticut, 1935 1979. AB - Trends in the incidence of childhood cancer in Connecticut are reported and analyzed for the period 1935-1979 by 5-year age groups (0-4, 5-9, 10-14, 15-19 years), using a log linear model method. A threefold increase (P less than .001) in the incidence of ALL in males 0-4 years of age was observed, with significant increases of smaller magnitude seen in males aged 5-9 and 15-19 and females aged 0-4 and 5-9. The incidence of central nervous system cancers also increased in several age groups for both sexes with the largest increase seen in males 0-4 years old. Significant increases in incidence of large magnitude were also observed for Hodgkin's disease, in males aged 15-19 years and females aged 10-19 years, for neuroblastoma in both sexes at ages 0-4 years, and for testis and ovarian cancer at ages 15-19 years. This study of trends in incidence of childhood cancers by 5-year age groups has revealed significant changes, which would not have been as apparent if broader age groups had been used. These results provide relevant data for investigating the etiology of cancer during infancy, childhood, and adolescence. Trends in Connecticut are compared with findings from other registries in the United States and other countries. PMID- 3352540 TI - Hematologic and clinical features of patients with chromosome 5 monosomy or deletion (5q). AB - This paper analyzes the hematologic features and outcome of 13 patients with chromosome 5 abnormalities (monosomy 5 or deletion of 5q), either isolated or with additional anomalies. Among four patients with isolated del (5q), two had a stable refractory macrocytic anemia with thrombocytosis (5q-syndrome). All nine patients with complex karyotypes had acute leukemia or refractory anemia with excess of blasts in acute transformation; two cases were TdT-positive, with a lymphoid or a mixed phenotype. In seven patients, preleukemia preceded overt leukemia, and in six, a prior therapeutic, or occupational exposure to mutagens/carcinogens had occurred. Additional chromosome 7 abnormalities were seen in four cases. The median survival of patients with complex karyotypes was 19 months from the time of diagnosis of the hematologic disorder and 5 months from the time of identification of the chromosome 5 abnormality. Pathogenetic implications of the chromosome 5 monosomy or del (5q) through a proto-oncogene activation and the putative hemopoietic stem cell involvement in a clonal disease are discussed. PMID- 3352541 TI - Malignant disease in the mothers of children with Ewing's tumour. AB - Previous research has shown that mothers of children with soft tissue sarcoma, osteosarcoma, and chondrosarcoma are at excess risk of developing breast cancer. The occurrence of malignant disease in the mothers of a population-based series of children with Ewing's sarcoma was investigated in order to determine whether these mothers were at excess risk of cancer and of breast cancer in particular. Sixty-one mothers were traced; there were two cases of breast cancer and two other registrable neoplasms. Risk of malignancy in the mothers was not in excess of expectation. PMID- 3352542 TI - Fine-needle aspiration biopsy in children: experience in 70 cases. AB - Results of 70 fine-needle aspiration biopsies (FNAB) were evaluated retrospectively in 61 pediatric patients. Over a period of 9 months all mass lesions suspected being malignant were aspirated. Twelve of the 70 aspirations were performed in children having known tumours, in order to exclude recurrence or metastasis. The others were carried out to obtain a diagnosis. Satisfactory specimens were obtained from 58 (83%). There were 21 benign diagnoses, 36 malignant diagnoses, and 1 with suspected malignancy. Correlation of histologic and cytologic diagnoses was possible in 45 cases. The diagnostic sensitivity and specificity were 95% and 80%, respectively. We have found FNAB more accurate in the diagnosis of malignancies than in benign lesions. The results suggest that this is a useful technique for obtaining a first diagnosis of malignancy, as well as for excluding recurrence or metastatic disease. PMID- 3352543 TI - Bulk flow model for multislice magnetic resonance imaging sequences with phantom validation. AB - A simple conceptual model for describing the effects of one-dimensional bulk flow on image intensities is presented and validated using a multislice imaging sequence specific to one vendor. The model allows quantitative estimates of echo amplitudes versus velocity by using the equation of motion to follow the pulse history of fluid volumes influenced by the readout pulse for any slice of interest. Each affected volume is divided into equal elemental components and the state of each component is computed at discrete times in a pulse position-timing diagram until readout occurs. The final amplitude for the composite volume is determined by the signed summation of each of the elemental components. Validation of the quantitative model was performed by imaging a rotating bulk flow phantom centered at each of the slices of a multislice, partial saturation, spin-echo sequence. Effects due to rf field inhomogeneities were normalized by dividing the results of the dynamic scans by the corresponding static one. The results presented here are relatively insensitive to odd-echo dephasing (even echo rephasing). PMID- 3352544 TI - A dose homogeneity index for evaluating 192Ir interstitial breast implants. AB - To evaluate and optimize dose homogeneity of 192Ir interstitial breast implants, we define a quantity, the dose homogeneity index (DHI), as follows: DHI = [V(TDR) -V(HDR)]/V(TDR), where V(TDR) denotes the total treatment volume enclosed by the prescribed treatment dose rate (TDR) and V(HDR) denotes the volume enclosed by high-dose rate (HDR), which is 1.5 X TDR or greater. We have used the DHI to examine and compare 192Ir double-plane implants of various sizes planned by the Memorial system or the Tufts system. Criteria have been suggested for the number of planes required for implants in a given treatment volume. Anderson's volume dose histogram with inverse square suppression is adopted for illustration. PMID- 3352545 TI - Solutions of two paramagnetic ions for use in nuclear magnetic resonance phantoms. AB - The introduction of paramagnetic ions to affect relaxation times has been used in a variety of nuclear magnetic resonance (NMR) applications. All such relaxants used in NMR phantoms to date have consisted of a single paramagnetic ion. The disadvantage of this is that only one relaxation time can be adjusted as desired, either T1 or T2. This study demonstrates that, by properly choosing two paramagnetic ions, it is possible to adjust both T1 and T2 independently over a wide range of values. Specifically, solutions of MnCl2 and NiCl2 were prepared that simultaneously matched target T1 and T2 values to within approximately 6%. PMID- 3352546 TI - Energy deposition patterns in an amputated human lower leg heated with a miniannular phased array. AB - The energy deposition patterns in both alcohol-fixed and unfixed amputated human lower legs produced by a miniannular phased array (MAPA) applicator have been determined. The nontumor bearing portions of four human legs, amputated for therapeutic purposes, were heated within the MAPA. Experimental measurements of the time rate of temperature rise at many locations inside the leg (between 125 and 150) were transformed to specific absorption rate (SAR) values at each point. A simple model was developed which predicts the axial variations in SAR inside the heated limb based upon quantitative details of the leg's geometry obtained from computerized tomography scans. The axial location of the region of maximum energy deposition was predicted by the model with a precision of approximately 1 to 2 cm. Significant time rate of temperature rise was measured inside the cortical portion of the tibia, while the temperature rise in the cancellous (marrow) portion of the tibia was negligible. The alcohol fixation process appears to have no significant effect on the energy deposition patterns within the various leg tissues. PMID- 3352547 TI - An algorithm for three-dimensional visualization of radiation therapy beams. AB - A computer algorithm to display radiation beams superimposed on three-dimensional (3-D) views of patient anatomy has been developed. It may be implemented as a postprocessing step to existing software for 3-D presentation and display. The algorithm takes as input a shaded 3-D view (reconstructed, for example, from computed tomography scans), together with the associated depth map, and generates as output an enhanced 3-D view highlighting in color the visible points which lie within the projected beam outlines. The algorithm is independent of the method used to generate the 3-D view (surface or volume rendering techniques may be used) and is independent of beam shape (beams may be modified with shielding blocks). It is not restricted to external surfaces and will correctly show radiation beams projected onto cut-away views of internal organs. The method is illustrated by application to a tangential pair for breast malignancy, using 3-D views generated with volume rendering software. PMID- 3352548 TI - Slit design considerations for rotating-aperture, scanning-beam radiography. AB - The rotating-aperture wheel (RAW) scanning-beam device is uniquely applicable for scatter elimination in short-time, rapid-sequence, and real-time radiographic imaging because of the continuous rotary motion of its slit pattern. This rotary motion places special restrictions on the slit pattern design. Although simple sector-shaped slits provide uniform primary transmission, they entail an unacceptable degree of slit widening on small-diameter wheels. The use of multiple slit zones with slits of different angular width has reduced the extent of this widening on a prototype RAW; however, interzone boundary artifacts caused by differential primary x-ray cutoff are apparent on some clinical images. This problem is eliminated with a unique spiral-shaped aperture pattern which consists of slits of constant width and constant spacing. Each slit is radially continuous and provides uniform primary transmission without interzone artifacts. This spiral pattern satisfies all requirements and appears to be the pattern of choice for rotating-aperture scanning-beam radiography. PMID- 3352549 TI - Characteristics of an ethylene-polyethylene high-pressure ionization chamber and its potential for deriving radiation dose and quality information in neutron gamma radiation fields. AB - A recently developed method for measuring dose and quality parameters in mixed neutron-gamma radiation fields is extended for neutron energy regions relevant to current neutron therapy. It is theoretically shown that if a polyethylene high pressure ionization chamber filled with a gas mixture of 95% ethylene and 5% carbon dioxide is used at suitable gas pressures, it may overcome the limitations found for a similar tissue-equivalent chamber and measure both the gamma ray absorbed dose-fraction and the mean incident neutron energy for neutrons between 0.1 and at least 30 MeV, if certain conditions exist. The simultaneous use of the polyethylene high-pressure ionization chamber as a conventional neutron dosimeter also allows determination of both the neutron and gamma ray absorbed doses. Estimated accuracies are 15% for the mean incident neutron energy and 15%-30% for the doses determination. The present method may complement currently available techniques as it presents certain advantages in situations where the neutron spectrum is poorly known. If coupled with other dosimeters, the accuracy of the method can be improved. PMID- 3352550 TI - The role of humidity and other correction factors in the AAPM TG-21 dosimetry protocol. AB - A detailed derivation is presented of the formulas required to determine Ngas and Dmed in the AAPM TG-21 dosimetry protocol. This protocol specifies how to determine the absorbed dose in an electron or photon beam when using exposure or absorbed dose calibrated ion chambers. It is shown that the expression given in TG-21's recent letter of clarification is incorrect. Accounting for humidity correctly increases, by 0.4%, all absorbed dose determinations using an exposure calibrated ion chamber. Taking into account other correction factors in the equation for exposure could also have varying, but significant effects (possibly over 1%). These are the stem scatter correction, the axial nonuniformity correction and the electrode correction for electrodes made of different materials from the wall. Attention is drawn to differences in the definitions of the exposure and absorbed dose calibration factors, Nx and ND, respectively, as supplied by the NBS and the NRCC. PMID- 3352551 TI - Two-dimensional dose distribution around a commercial 125I seed. AB - The Monte Carlo method was used to investigate the dose distribution around a 3M Company model 6711 125I seed immersed in a water phantom. Dose rate per unit activity data are presented as a matrix of 63 points surrounding the seed. Relative dose data are presented graphically for two mutually perpendicular directions and compared with the corresponding data for the only other 125I seed currently available, the 3M Company model 6702 125I seed. The 6711 relative dose distribution decreases more rapidly with distance from the seed than does the 6702 relative dose distribution. Uncertainties in the 6711 seed dose distribution produced by end-weld thickness variations were investigated and found to be substantial at certain points. PMID- 3352552 TI - Problems with organic materials for magnetic resonance imaging phantoms. AB - Organic liquids are frequently used as magnetic resonance (MR) phantom materials. It is often not appreciated that indirect spin-spin coupling can dramatically affect signal amplitudes in spin-echo experiments. These effects are evidenced in three ways: (1) modulation of spin-echo amplitudes; (2) decrease in measured T2 relaxation times; and (3) dependence of spin-echo modulation and measured T2 values on the echo time (TE) in multiecho Carr-Purcell-Meibroom-Gill experiments. This paper illustrates these effects and warns against the inappropriate use of organic liquids as MR phantoms. PMID- 3352553 TI - Dependence of noise on array width and depth in digital radiography. AB - Measurements are reported for the image noise levels in digital radiographs using 256(2), 256(2)-zoom, 512(2), and 1024(2) storage arrays. The noise was essentially the same with 256(2)-zoom or 512(2) arrays, while it was 25% lower for a 256(2) array, and only 15% larger for a 1024(2) array than for a 512(2) array. Compatibility of these results with different models is evaluated. Also the number of bits/pixel was varied to determine the effect on noise; noise before digitization ranged from 4.3 to 0.13 gray levels. The noise level was found to be increased only if the noise was less than approximately one-half of a gray level. PMID- 3352554 TI - Total inhomogeneity correction including chemical shifts and susceptibility by view angle tilting. AB - A correction technique of the total magnetic field inhomogeneity effects including the localized object induced inhomogeneities such as chemical shift and susceptibility is developed and its usefulness is experimentally demonstrated. With this new and simple technique all the inhomogeneity induced artifacts can be corrected simultaneously. The basic idea of this method is to add a compensation gradient of the same amplitude as the selection gradient in simultaneity with the reading gradient in such a way that the view angle is tilted. Thereby all the inhomogeneity induced geometrical shifts and hence the intensity changes are corrected, since the addition of the compensation which is independent from the field inhomogeneities including both chemical shifts and susceptibility. This technique has been theoretically examined and its usefulness is demonstrated by experiments. PMID- 3352555 TI - [Choledochal cyst simulating a septated gallbladder]. PMID- 3352556 TI - [Development of psychosomatic medicine from the history of body-soul dualism]. PMID- 3352557 TI - [Ganglioside therapy in uremic polyneuropathy]. PMID- 3352558 TI - [Perthoracic needle biopsy in the diagnosis of pulmonary coin lesions. Results and complications]. PMID- 3352559 TI - [Improvement in leukocyte rheology with pentoxifylline]. PMID- 3352560 TI - [Acute febrile neutrophilic dermatosis: Sweet syndrome]. PMID- 3352561 TI - [Clinicopathologic conference. Incidental finding of primary hemochromatosis at an early stage? Differential diagnostic considerations]. PMID- 3352562 TI - [Score systems optimize intensive care medicine]. PMID- 3352563 TI - [Listeria meningitis after eating cheese]. PMID- 3352564 TI - Fetal alcohol syndrome in families. AB - A retrospective study of the clinical literature of fetal alcohol syndrome (FAS) was conducted to determine the incidence of FAS among younger and older siblings of a patient with FAS. The incidence of the disorder among older sibs was 170 per 1,000 whereas among younger sibs the incidence was 771 per 1,000. Since the risk for FAS in the general population is 1.9 per 1,000, these results clearly indicate the high risk of FAS among siblings if one sib is diagnosed as FAS. PMID- 3352566 TI - Response force titration for the assessment of the neuromuscular toxicity of 2,5 hexanedione in rats. AB - A silent, non-moving glass lever combined with strain gauges and mounted in an operant chamber measured the vertical isometric force exerted by the forepaw of rats. Every weekday the rats were subjected to a force titration schedule consisting of a sequence of discrete trials signalled by a lever light. The required force, above which a water reinforcement is delivered, was regulated by a generalized bisection algorithm. A stable force level which the rat was able to attain at 50% of the trials was quickly reached in each session by this algorithm. This technique was used to measure the neuromuscular performance decrement due to repeated 2,5-hexanedione treatment (250 and 500 mg/kg/day per os). The results were compared with fore- and hindlimb grip strength measurements on the same animals. This experiment showed that the force titration technique is able to distinguish between motivational and true force decrements, a distinction which cannot be made by the grip strength technique. PMID- 3352565 TI - Maternal age as a factor in determining the reproductive and behavioral outcome of rats prenatally exposed to ethanol. AB - Nulliparous Long-Evans rats were bred at one of four different ages and assigned to one of three treatment groups within each age condition. Maternal ages were 9, 18, 32, and 36 weeks. Treatment groups were ethanol (E), administered by gavage as 8 g/kg in two divided doses on days 10-14 of gestation, pair-fed (PF) controls, administered as an isocaloric sucrose solution by gavage on days 10-14 of gestation, and ad lib fed controls (C). All offspring were surrogate fostered shortly after delivery to untreated recently parturient dams. Litter sizes were standardized to 8 on the day of birth. Offspring were assessed longitudinally for growth, mortality, and behavior (olfaction, locomotor activity, maze learning, avoidance acquisition and startle). Approximately 85% of the 36 week old dams did not produce viable litters. In the remaining maternal age conditions, ethanol delayed offspring olfactory orientation and increased locomotor activity, the latter dissipating after 50-60 days of age. These ethanol-related effects occurred independent of maternal age condition. Maternal age, independent of ethanol, was a factor which reduced litter size and offspring weight up to 50 days, but produced few effects on behavior. The combination of maternal age and prenatal ethanol interacted to increase pregnancy loss (oldest maternal age), reduce offspring weight up to day 99 (oldest and middle maternal age), alter olfactory orientation performance (oldest and middle maternal age), reverse the typical ethanol-induced increase in activity for males in the figure-8 test (oldest maternal age group), shift the pattern of open-field activity, and change errors in a complex water maze. Not all of these interactions turned out to be specific to the ethanol X old maternal age condition. Several of the interactions occurred in both the old and middle maternal age conditions. The only effect of old maternal age that interacted strongly with ethanol was in their combined effects on reproduction. Here the combination of the two factors increased maternal mortality, the number of early pregnancy losses, and the number of litters where all members were dead or resorbed. It was concluded that short-term prenatal ethanol combined with advanced maternal age produces additive interactions on pregnancy success without affecting longer-term outcomes, while young maternal age showed no clear detrimental effects compared to the middle maternal age reference group. PMID- 3352567 TI - Go/no-go discriminated avoidance learning in prenatally x-irradiated rats. AB - Male Fischer344 rats were exposed to x-irradiation at a dose of 200 rad on Day 17 of gestation. Irradiated and control rats were tested at 10-13 weeks of age with the paradigm of go/no-go (active-passive) discriminated avoidance conditioning for three consecutive daily sessions. During the first conditioning session, they learned only active avoidance responses to two different warning signals. During the second and third sessions, they learned active and passive avoidance responses: in response to one warning signal, rats were required to make an active response to avoid a shock, but not to run in response to the other signal in order to avoid a shock. Prenatally irradiated rats made more active avoidance responses to both warning signals than controls (first session). In the early training phase of the go/no-go task, irradiated rats performed significantly higher active and lower passive avoidance responses than controls. Irradiated rats established a strong tendency to respond actively to the no-go signal, but eventually learned to respond to it. PMID- 3352568 TI - Short duration exposures to organic solvents: the relationship between neurobehavioral test results and other indicators. AB - Short duration exposure to solvents at even low concentrations can induce signs of mild toxicity such as mucous membrane irritation, tearing, nasal irritation, headache, and nausea. These irritant effects are often used as warning properties for potential solvent toxicities and have frequently been classified in the literature as pre-narcotic effects. With higher exposures the toxic effects are more pronounced and can include intoxication, incoordination, exhilaration, sleepiness, stupor, and the beginning stages of anesthesia. Collectively these effects are taken as indicators of narcosis. Offering recommendations for safe exposure limits for these shorter term exposures is made difficult because, (1) the mild toxic effects are often reported subjectively and tolerance usually develops, (2) the solvent concentration(s) cannot be documented in all cases, and (3) the effects are reversible when individuals are removed from exposure. Laboratory experiments involving controlled exposures to solvents using neurobehavioral performance tests represent one form of investigation that can provide meaningful information in this instance. The results can be viewed in two ways with reference to issues of safe exposure limits. One is to ensure that performance functions that can compromise safety are not affected by the exposure limits prescribed. The second is to consider performance changes due to short term exposures as possible precursors of similar but more severe effects given longer term exposures. Thus, setting exposure limits to protect against these performance changes could possibly prevent the development of more serious cases of chronic solvent neurotoxicity. This paper compares solvent concentrations from short-duration exposure studies using neurobehavioral tests with the concentrations producing irritant and narcotic effects, as documented by the two main standards recommending bodies, the National Institute for Occupational Safety and Health and the American Conference of Governmental Industrial Hygienists. Comparisons are also made with the regulatory exposure limits established by the Occupational Safety and Health Administration. In general, the neurobehavioral changes which occur following short-duration exposures are reported at concentrations between those which produce irritant effects and narcosis. For the chemicals which have been tested, the performance changes measured by the present day neurobehavioral tests in use rarely occur at or below those limits recommended by the standards recommending bodies. PMID- 3352569 TI - Dose-dependent consequences of cocaine on pregnancy outcome in the Long-Evans rat. AB - The number of obstetric patients abusing cocaine has increased dramatically in recent years. To better understand its effect on pregnancy and to establish the LD50s for maternal and fetal fatalities, the dose-dependent effects of cocaine on pregnancy outcome were investigated in the Long-Evans rat. Pregnant animals were given either saline or 40, 50, 60, 70, 80, or 90 mg/kg cocaine hydrochloride from gestation days 7 to 19 inclusive. An additional group was non-treated and had ad lib access to food and water. Animals were sacrificed on gestation day 20 and the fetuses were examined. Despite treatment during the major periods of organogenesis and brain development, few congenital abnormalities were observed. There were, however, dose-dependent effects on maternal weight gain, maternal food and water consumption, fetal weight, maternal and fetal fatalities, fetal edema, abruptio placentae and cephalic hemorrhages. Despite suppression of maternal weight gain, there was preservation of fetal weights at cocaine doses up to and including 80 mg/kg/day, suggesting some protection of fetal growth. In addition to providing information on the gestational effects of cocaine in the rat, the present study provides information useful in guiding the selection of cocaine doses for subsequent behavioral teratology studies. PMID- 3352570 TI - Prenatal alcohol exposure and offspring hyperactivity: effects of physostigmine and neostigmine. AB - Rats were fed a liquid diet containing ethanol from days 6-19 of gestation. Controls were pair-fed the same diet with sucrose substituted for ethanol, or received ad lib chow and water. The activity of the offspring was observed at 10, 16, 22 or 28 days-of-age. Overall, offspring exposed to alcohol prenatally were hyperactive compared to controls at 16 and 22 days, but not at 10 or 28 days. Administration of physostigmine had no effect on the activity of any group at 10 days. At 16 days, physostigmine enhanced the activity of the alcohol group, had no effect on the sucrose group, but depressed the activity of the chow group. At 22 days it led to a dose-related decrease in activity in controls but had no effect on the activity of the alcohol treated pups. At 28 days, physostigmine decreased the activity of all three groups. Administration of the quaternary derivative, neostigmine, indicated that the effects of scopolamine at 22 days were probably central in origin. These data indicate that a putative cholinergic/inhibitory system becomes functional in control pups before 22 days, but in pups exposed to alcohol prenatally development is delayed by a number of days. PMID- 3352571 TI - The contribution of primary and secondary neuronal degeneration to prenatally induced micrencephaly. AB - Prenatal exposure of rats to the alkylating agent methylazoxymethanol acetate (MAM Ac) induces severe micrencephaly in the offspring. The aim of the present study was to examine the contribution of primary cell death (due to a direct action of MAM Ac on the neuroepithelium), and secondary (target-dependent) cell death to the subsequent cell deficits in the visual system following prenatal exposure to MAM Ac on embryonic day 11, 12, 13, 14, 15 or 16. The results showed that when primary cell death substantially reduced the neuronal population of a target structure then there was increased target-dependent cell death in the neurons which normally project to that target. This was particularly evident in the dorsal lateral geniculate nucleus following exposure to MAM Ac on E15. Although the MAM Ac caused virtually no primary cell death in the embryonic precursor cells of the dLGN, the nucleus in the adult offspring was reduced by 87% compared with controls. This reduction was shown to be due to increased postnatal target-dependent, or secondary, cell death due to a severe reduction in layers III and IV of the occipital cortex. The cortical damage was due to primary cell death. Hence, primary cell death only partly accounts for the degree of micrencephaly seen in the offspring, consideration of secondary cell death is necessary to understand the total deficit. PMID- 3352573 TI - 2,4-D-n-butyl ester (2,4-D ester) induced ataxia in rats: role for n-butanol formation. AB - Three formulations of 2,4-D were tested in rats for their ability to increase landing foot splay, a measure of ataxia. When administered for three to four consecutive days, 2,4-D-n-butyl ester (150 mg/kg/day SC) produced significant increases in landing foot splay while 2,4-D acid (120 mg/kg/day SC) and 2,4-D mixed butyl esters (150 mg/kg/day SC) did not. The ability of acute n-butanol, 2 butanol, and a 50:50 mixture of both (2.13 mM/kg SC) to increase landing foot splay was then assessed. Only n-butanol significantly increased landing foot splay. Similarly, when n-butanol was administered daily, at doses corresponding to 150 mg/kg/day of the 2,4-D-n-butyl ester, significant increases in landing foot splay were evident. The pattern of splay increases was remarkably similar to that observed for 2,4-D-n-butyl ester. When locomotor activity was the dependent variable, daily n-butanol had no effect. These results suggest that in vivo formation of n-butanol after administration of 2,4-D-n-butyl ester is responsible for the motor incoordination but not the depression of locomotor activity observed following 2,4-D-n-butyl ester administration. These data demonstrate that different formulations of the same herbicide can produce differential behavioral effects. PMID- 3352572 TI - Neurobehavioral toxicity of 2,4-D-n-butyl ester (2,4-D ester): tolerance and lack of cross-tolerance. AB - Daily administration of 2,4-dichlorophenoxyacetic acid-n-butyl ester to rats (2,4 D ester, 150 mg/kg/day SC) initially produced depressions in photocell locomotor activity and increases in landing foot splay. Maximal tolerance developed to these effects following ten days of repeated exposure. By themselves, physostigmine sulfate (0.01-0.10 mg/kg) and (0.3-10.0 mg/kg) n-butanol produced locomotor activity depression in a dose-related manner. n-Butanol produced increases in landing foot splay while physostigmine had no effect at the doses employed. No cross-tolerance was observed between 2,4-D ester and physostigmine sulfate or n-butanol when locomotor activity was the dependent variable. Similarly, a lack of cross-tolerance was observed between 2,4-D ester and n butanol when landing foot splay was measured. Unlike physostigmine, prior exposure to n-butanol tended to enhance its toxicity upon subsequent exposures, an effect which was blocked when 2,4-D ester was administered between n-butanol exposures. PMID- 3352574 TI - Continuing professional education, continued learning or refreshment? PMID- 3352575 TI - Conversion courses: the views of British enrolled nurses. PMID- 3352576 TI - Computers and nursing education in one Australian tertiary institution. PMID- 3352577 TI - Encouraging students to be research minded. PMID- 3352578 TI - AIDS and general nursing training curricula: a survey of UK schools of nursing. PMID- 3352580 TI - The use of an extended simulation in ward management training (1): Rationale for development and design criteria. PMID- 3352581 TI - Nurse education in Sweden. PMID- 3352579 TI - Recruitment--the graduate nurse. PMID- 3352582 TI - The development of a conceptual framework for mental handicap nursing practice in the UK. PMID- 3352583 TI - The dilemma of moral and ethical decision making in the intensive care nursery. PMID- 3352584 TI - The positive effects of positioning. PMID- 3352585 TI - Dysrhythmias in infancy. PMID- 3352586 TI - Preparing a family for home monitoring. PMID- 3352587 TI - Factors influencing men's transition into parenthood. PMID- 3352588 TI - Comparisons of axillary and rectal temperatures in the preterm infant. PMID- 3352589 TI - Dilemmas in the care of impaired infants: effects on nursing and health care. PMID- 3352590 TI - Nursing management of the human response to the premature birth experience. PMID- 3352591 TI - The case of baby Alice: AIDS/ARC in infancy. PMID- 3352592 TI - Characteristics of the interaction of anthrapyrazole anticancer agents with deoxyribonucleic acids: structural requirements for DNA binding, intercalation, and photosensitization. AB - The binding constants for interaction of several novel anthra[1,9-cd]pyrazol 6(2H)-ones (anthrapyrazoles) with DNA have been determined by an ethidium displacement method. The apparent binding constants range from less than 2 X 10(6) to 2.7 X 10(8) M-1. The binding is influenced not only by the nature of the side chains but also by the number and position of hydroxyl groups on the chromophore. Unwinding angles, determined by a topoisomerase I assay, ranged from 0 degrees to 29.2 degrees. The deshydroxy compound 1 gave the highest unwinding angle, and both substitution of hydroxyl groups in the chromophore and alterations in the side chains decrease the unwinding angle, consistent with a decreased or partial intercalation. Representative anthrapyrazoles cause an increase in sonicated DNA viscosity as expected for intercalators. Spectrophotometric examination of the binding of compound 1 to DNAs of different base composition show that the apparent binding to GC is approximately 3 times that of AT, a result which was paralleled by thermal denaturation studies. Certain of the anthrapyrazoles exhibit marked visible light photosensitization and induce DNA single-strand breakage upon illumination in the presence of NADH. The essential structural requirement for photosensitizing properties with these agents was the absence of hydroxyl groups in the chromophore. By employing 32P labeled DNA of known sequence, it was possible to examine the anthrapyrazole 1 photosensitized cleavage of DNA at the individual base level employing denaturing polyacrylamide sequencing gels. Smooth sequence neutral photosensitized cleavage of DNA is observed analogous to hydroxyl radical "footprinting." PMID- 3352593 TI - The distribution of cytochrome P-450 monooxygenase in cells of the rabbit lung: an ultrastructural immunocytochemical characterization. AB - The cytochrome P-450 monooxygenase system of the mammalian lung is known to be associated with the microsomal subcellular fraction and has been demonstrated in two pulmonary cell types rich in endoplasmic reticulum: Clara cells and type II pneumocytes. However, analysis of ultracellular fractions, isolated cell preparations, or light microscopic immunohistochemical studies of tissue sections has permitted only limited resolution of the distribution of this enzyme system within the 40 or more cell types of the lung. Therefore, we have used the greater resolving power of transmission electron microscopy and immunogold labeling to characterize the cellular and subcellular distribution of the cytochrome P-450 system in the lung. In Lowicryl-embedded sections of lung from adult rabbits, antisera (1:10,000) against the constitutive pulmonary microsomal cytochrome P 450 monooxygenase isozymes 2 and 5 and NADPH-cytochrome P-450 reductase (anti-2, anti-5 and anti-R) bound specifically to regions known to be rich in agranular endoplasmic reticulum (AER) in the cytoplasm of Clara cells. The plasma membranes of bronchiolar Clara cells, the tips of microvillae of ciliated cells, secretory granules of goblet cells, and the cell membrane and pinocytotic vesicles of endothelial cells were all intensely labeled with anti-2 and anti-5 but not with anti-R, even at a 10-fold higher concentration. The intensity of labeling of AER in Clara cells with anti-R and anti-2, but not anti-5, appeared to correlate positively with the cellular content of secretory granules. The Golgi membranes of ciliated cells were labeled intensely with anti-5 only. The plasma membrane of type II pneumocytes was not labeled by any of the antisera, but with anti-2 or anti-5 there was labeling of AER-associated vacuoles, the membranous residue of lamellar bodies, and, to some extent, mitochondria; at 1:5,000 but not 1:10,000 dilution, staining with anti-R was qualitatively similar. Type I pneumocytes, ciliated cell cytoplasm, and nuclei were essentially unlabeled. Immunoblots (Western) of tracheal homogenates yielded no evidence for epitopes other than those in microsomal fractions from whole lung. Contact blots of fresh whole trachea, before but not after lavage, bound anti-2 and anti-R. Thus, we have demonstrated for the first time that components of the pulmonary cytochrome P-450 monooxygenase, although localized in the AER-rich regions of the Clara cells and type II pneumocytes, are not restricted to these cell types or to the endoplasmic reticulum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3352594 TI - Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model. AB - Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia. A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as "nonclassical" cannabinoid analgetics that conform to this agonist-receptor three-point interaction model. At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor. A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro. Enantio- and stereoselectivity were exhibited by the nonclassical cannabinoid compounds for both the analgetic response and the ability to inhibit adenylate cyclase. The magnitude of the enantioselective response was equal for both the biochemical and physiological endpoints. Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo. A conceptualization of the cannabinoid analgetic receptor is presented. PMID- 3352596 TI - External location of sites on pig erythrocyte membranes that bind nitrobenzylthioinosine. AB - Nucleoside transport in erythrocytes of various species is inhibited by the binding of nitrobenzylthioinosine (NBMPR) to high affinity sites associated with nucleoside transport elements of the plasma membrane. The present study examined binding of [3H]NBMPR to unsealed ghosts and to sealed right-side-out vesicles (ROVs) and inside-out vesicles (IOVs) prepared from pig erythrocytes. Kd values for NBMPR dissociation from the ligand-site complex in unsealed ghosts, ROVs and IOVs were similar (1.6-2.4 nM), and Bmax values (mean +/- SD) were, respectively, 22.2 +/- 5.5, 25.8 +/- 6.4, and 37.3 +/- 4.0 molecules/fg of protein, reflecting differences in the protein content of the membrane preparations. When temperatures were decreased from 22 degrees to 4 degrees, NBMPR binding to erythrocyte membrane preparations was reduced in IOVs relative to that in unsealed ghosts and ROVs. At 22 degrees, the association of NBMPR molecules with IOVs was slower than with ROVs and unsealed ghosts, differences that were virtually eliminated by permeabilization of the membrane preparations with saponin. Thus, the binding sites were more accessible to external NBMPR in sealed ROVs and unsealed ghosts than in sealed IOVs, indicating that the NBMPR sites are located on the extracellular aspect of the membrane. PMID- 3352595 TI - Identification of serotonin 5-HT3 recognition sites in membranes of N1E-115 neuroblastoma cells by radioligand binding. AB - [3H]ICS 205-930 recognition sites were analyzed in membranes prepared from murine neuroblastoma N1E-115 cells. [3H]ICS 205-930 bound rapidly, reversibly, and stereoselectively to a homogeneous population of high affinity recognition sites: Bmax = 40 +/- 5 fmol/mg of protein, pKD = 9.20 +/- 0.05 (n = 11). Nonlinear regression and Scatchard analysis of saturation data suggested the existence of a single class of [3H]ICS 205-930 recognition sites on N1E-115 cells. The affinity of [3H]ICS 205-930 determined in kinetic studies was in agreement with that obtained under equilibrium conditions. Competition studies carried out with a large variety of agonists and antagonists also suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. [3H]ICS 205-930 binding sites displayed the pharmacological profile of a 5-HT3 receptor. Potent 5 HT3 receptor antagonists showed nM affinities for [3H]ICS 205-930-binding sites with the following rank order of potency: SDZ 206-830 greater than SDZ 206-792 greater than ICS 205-930 greater than BRL 43694 greater than quipazine greater than BRL 24924 greater than MDL 72222 greater than GR 38032F. Methiothepine, mCPP, and metoclopramide showed sub-microM affinity. The rank order of potency of agonists was: 5-HT greater than phenylbiguanide = 2-methyl-5-HT much greater than 5-methoxytryptamine = 5-carboxamidotryptamine. All antagonist competition curves were steep (pseudo-Hill coefficients not lower than 1), monophasic, and best fit for a one-site model; 5-HT and 2-methyl-5-HT produced pseudo-Hill coefficients of 1.2-1.4. Drugs acting at 5-HT1, 5-HT2, alpha- and beta-adrenergic, dopaminergic, and histaminergic receptors (methysergide, ketanserin, propranolol, phentolamine, sulpiride, SCH 23390, cimetidine) were essentially inactive at 10 mumol/liter. The binding of [3H]ICS 205-930 was not affected by guanine and adenine nucleotides (GTP, GppNHp, and ATP) at 1 mmol/liter. These nucleotides did not affect the binding of agonists, suggesting that 5-HT3 recognition sites are not coupled to G-proteins. The interactions of agonists and antagonists with [3H]ICS 205-930 recognition sites were competitive in nature, as demonstrated by saturation experiments carried out with [3H]ICS 205-930 in the presence and the absence of unlabeled compounds: apparent Bmax values were not reduced, whereas apparent KD values were increased in the presence of competing ligands.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 3352598 TI - Inhibition of repair patch ligation by an inhibitor of poly(ADP-ribose) synthesis in normal human fibroblasts damaged with ultraviolet radiation. AB - The effect of inhibiting poly(ADP-ribose) synthesis on DNA excision repair following UV irradiation of cultured normal human fibroblasts was determined under conditions which did not perturb NAD+ concentration. Following UV irradiation, there was a transient increase in DNA strand breaks to a maximum of 800 rad eq of breaks 30 min after damage. 3-Aminobenzamide (5 mM) caused a 50% increase in the maximum number of DNA single strand breaks following damage but did not prevent the decline in strand breaks which normally occurs within the first hour after damage. Addition of 3-aminobenzamide several hours after damage, when most of the strand breaks had disappeared, caused a reaccumulation of strand breaks. 3-Aminobenzamide inhibited ligation of repair patches, as measured by exonuclease III, following damage by UV radiation and the magnitude of the inhibition was sufficient to account for the increases in strand breaks caused by 3-aminobenzamide. UV radiation alone did not lower NAD+ concentrations; however, when the repair synthesis step was inhibited by aphidicolin and hydroxyurea, the number of single strand breaks increased and the NAD+ concentration fell to 11%. 3-Aminobenzamide inhibited this depletion of NAD+ by 80%. PMID- 3352597 TI - Mechanism of halothane-induced inhibition of isoproterenol-stimulated lipolysis in isolated rat adipocytes. AB - The effect of halothane on isoproterenol-stimulated lipolysis was determined in isolated rat epididymal fat cells. The maximal lipolytic response (Emax) activated by isoproterenol was 350 +/- 61 nmol of glycerol/10(5) cells/hr with an EC50 of 5.1 X 10(-9) M. When the adipocytes were simultaneously bubbled with 2.5% halothane, the Emax decreased to 158 +/- 43 nmol of glycerol/10(5) cells/hr and the dose response curve for isoproterenol was shifted to the right (EC50 3.5 X 10(-8) M, p less than 0.05). When lipolysis was maximally stimulated with (-) isoproterenol (10(-6)M), the inhibitory effect of halothane was found to be both dose dependent (IC50 approximately 2.5%, v/v) and reversible following washout. Neither the nonhydrolyzable cAMP analog, 8-(4-chlorophenylthio) adenosine 3',5' cyclic monophosphate (2 X 10(-3)M), nor forskolin (10(-6) M) was able to normalize lipolysis in the presence of halothane. The activation of cAMP dependent protein kinase (EC 2.7.1.37) activity by isoproterenol was not different in halothane-exposed cells when compared to unexposed cells. When control adipocytes were exposed to isoproterenol (10(-6) M), there was a 2.5-fold increase in the activity of hormone-sensitive lipase (EC 3.1.1.3) from 0.64 +/- 0.13 to 1.53 +/- 0.32 pkat (pmol/sec) per mg (p less than 0.005, n = 10). However, in the presence of halothane (2.5%, v/v) isoproterenol stimulation of hormone-sensitive lipase was attenuated by 50% to values of 1.06 +/- 0.23 pkat/mg (p less than 0.01, n = 10). Halothane had no direct inhibitory effect on hormone sensitive lipase since this enzyme's activity was unaffected when homogenates of isoproterenol-stimulated control cells were incubated with halothane. These studies suggest that halothane impairs the activation of hormone-sensitive lipase by cAMP-dependent protein kinase and in this manner inhibits beta-adrenergic stimulated lipolysis. PMID- 3352599 TI - Polymerase III transcription factor B activity is reduced in extracts of growth restricted cells. AB - Extracts of cells that are down-regulated for transcription by RNA polymerase I and RNA polymerase III exhibit a reduced in vitro transcriptional capacity. We have recently demonstrated that the down-regulation of polymerase I transcription in extracts of cycloheximide-treated and stationary-phase cells results from a lack of an activated subform of RNA polymerase I which is essential for rDNA transcription. To examine whether polymerase III transcriptional down-regulation occurs by a similar mechanism, the polymerase III transcription factors were isolated and added singly and in pairs to control cell extracts and to extracts of cells that had reduced polymerase III transcriptional activity due to cycloheximide treatment or growth into stationary phase. These down-regulations result from a specific reduction in TFIIIB; TFIIIC and polymerase III activities remain relatively constant. Thus, although transcription by both polymerase III and polymerase I is substantially decreased in extracts of growth-arrested cells, this regulation is brought about by reduction of different kinds of activities: a component of the polymerase III stable transcription complex in the former case and the activated subform of RNA polymerase I in the latter. PMID- 3352600 TI - Neoplastic transformation induced by an activated lymphocyte-specific protein tyrosine kinase (pp56lck). AB - The lck proto-oncogene encodes a lymphocyte-specific member of the src family of protein tyrosine kinases. Here we demonstrate that pp56lck is phosphorylated in vivo at a carboxy-terminal tyrosine residue (Tyr-505) analogous to Tyr-527 of pp60c-src. Substitution of phenylalanine for tyrosine at this position resulted in increased phosphorylation of a second tyrosine residue (Tyr-394) and was associated with an increase in apparent kinase activity. In addition, this single point mutation unmasked the oncogenic potential of pp56lck in NIH 3T3 cell transformation assays. Viewed in the context of similar results obtained with pp60c-src, it is likely that the enzymatic activity and transforming ability of all src-family protein tyrosine kinases can be regulated by carboxy-terminal tyrosine phosphorylation. We further demonstrate that overexpression of pp56lck in the murine T-cell lymphoma LSTRA as a result of a retroviral insertion event produces a kinase protein that despite wild-type primary structure is nevertheless hypophosphorylated at Tyr-505. Thus, control of normal growth in this lymphoid cell line may have been abrogated through acquisition of a posttranslationally activated version of pp56lck. PMID- 3352601 TI - The human c-fps/fes gene product expressed ectopically in rat fibroblasts is nontransforming and has restrained protein-tyrosine kinase activity. AB - A 13-kilobase EcoRI genomic restriction fragment containing the human c-fps/fes proto-oncogene locus was expressed transiently in Cos-1 monkey cells and stably in Rat-2 fibroblasts. In both cases, human c-fps/fes directed synthesis of a 92 kilodalton protein-tyrosine kinase (p92c-fes) indistinguishable from a tyrosine kinase previously identified with anti-fps antiserum which is specifically expressed in human myeloid cells. Transfected Rat-2 cells containing approximately 50-fold more human p92c-fes than is found in human leukemic cells remained morphologically normal and failed to grow in soft agar. Synthesis of p92c-fes in this phenotypically normal line exceeded that of the P130gag-fps oncoprotein in a v-fps-transformed Rat-2 line. Despite this elevated expression, human p92c-fes induced no substantial increase in cellular phosphotyrosine and was not itself phosphorylated on tyrosine. In contrast, p92c-fes immunoprecipitated from these Rat-2 cells or expressed as an enzymatically active fragment in Escherichia coli from a c-fps/fes cDNA catalyzed tyrosine phosphorylation with an activity similar to that of v-fps/fes polypeptides. Thus, p92c-fes is not transforming when ectopically overexpressed in Rat-2 fibroblasts. This lack of transforming activity correlates with a restriction imposed on the kinase activity of the normal c-fps/fes product in vivo which is apparently lifted for v-fps/fes oncoproteins, suggesting that regulatory interactions within the host cell modify fps/fes protein function and normally restrain its oncogenic potential. PMID- 3352602 TI - The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing. AB - Tropomyosin (TM), a ubiquitous protein, is a component of the contractile apparatus of all cells. In nonmuscle cells, it is found in stress fibers, while in sarcomeric and nonsarcomeric muscle, it is a component of the thin filament. Several different TM isoforms specific for nonmuscle cells and different types of muscle cell have been described. As for other contractile proteins, it was assumed that smooth, striated, and nonmuscle isoforms were each encoded by different sets of genes. Through the use of S1 nuclease mapping, RNA blots, and 5' extension analyses, we showed that the rat alpha-TM gene, whose expression was until now considered to be restricted to muscle cells, generates many different tissue-specific isoforms. The promoter of the gene appears to be very similar to other housekeeping promoters in both its pattern of utilization, being active in most cell types, and its lack of any canonical sequence elements. The rat alpha TM gene is split into at least 13 exons, 7 of which are alternatively spliced in a tissue-specific manner. This gene arrangement, which also includes two different 3' ends, generates a minimum of six different mRNAs each with the capacity to code for a different protein. These distinct TM isoforms are expressed specifically in nonmuscle and smooth and striated (cardiac and skeletal) muscle cells. The tissue-specific expression and developmental regulation of these isoforms is, therefore, produced by alternative mRNA processing. Moreover, structural and sequence comparisons among TM genes from different phyla suggest that alternative splicing is evolutionarily a very old event that played an important role in gene evolution and might have appeared concomitantly with or even before constitutive splicing. PMID- 3352603 TI - Effects of single-base substitutions within the Acanthamoeba castellanii rRNA promoter on transcription and on binding of transcription initiation factor and RNA polymerase I. AB - Single-point mutations were introduced into the promoter region of the Acanthamoeba castellanii rRNA gene by chemical mutagen treatment of a single stranded clone in vitro, followed by reverse transcription and cloning of the altered fragment. The promoter mutants were tested for transcription initiation factor (TIF) binding by a template commitment assay plus DNase I footprinting and for transcription by an in vitro runoff assay. Point mutations within the previously identified TIF interaction region (between -20 and -47, motifs A and B) indicated that TIF interacts most strongly with a sequence centered at -29 and less tightly with sequences upstream and downstream. Some alterations of the base sequence closer to the transcription start site (and outside the TIF-protected site) also significantly decreased specific RNA synthesis in vitro. These were within the region which is protected from DNase I digestion by polymerase I, but these mutations did not detectably affect the binding of polymerase to the promoter. PMID- 3352604 TI - Amplification and expression of heterologous ornithine decarboxylase in Chinese hamster cells. AB - We have developed an amplifiable mammalian expression vector based on the enzyme ornithine decarboxylase (ODC). We show greater than 700-fold amplification of this vector in ODC-deficient Chinese hamster ovary cells. A passive coamplified marker, dihydrofolate reductase (dhfr), was amplified and overexpressed 1,000 fold. This ODC vector was a dominant marker in a variety of cell types and displayed at least 300-fold amplification in wild-type Chinese hamster ovary cells. PMID- 3352605 TI - A novel hsp70-like protein (P70) is present in mouse spermatogenic cells. AB - Mouse spermatogenic cells contain relatively large amounts of a 70-kilodalton protein (P70) that is closely related to hsp70, the major inducible heat shock protein. When hsp70 from spermatogenic cells is heat induced, it migrates to the same location as does P70 on two-dimensional polyacrylamide gels, indicating that it has an apparently identical mass and isoelectric point. P70 reacts strongly and specifically with an anti-Drosophila hsp70 monoclonal antibody that is specific for products of the hsp70 gene family. Both P70 and hsp70 are also ATP binding proteins and are purified by using ATP-affinity chromatography. However, P70 and hsp70 are unique proteins on the basis of peptide map analysis and are regulated differently in germ cells. P70 appears to be a novel heat shock protein of spermatogenic cells which is synthesized in association with germ cell differentiation. PMID- 3352606 TI - Stable variant-specific transcripts of the variant cell surface glycoprotein gene 1.8 expression site in Trypanosoma brucei. AB - The structure and transcriptional regulation of the 1.8 variant cell surface glycoprotein (VSG) gene expression site located on a 430-kilobase (kb) chromosome was examined in a 430-kb-chromosome-specific library. Using 32P-labeled nascent transcripts generated by nuclear run-on, we selected recombinant clones derived from the 430-kb chromosome which were coordinately activated with the 1.8 VSG gene. The results show that a repetitive region with a minimum size of 27 kb is coordinately activated with the 1.8 VSG gene. As with the 1.8 VSG gene, transcription is by RNA polymerases that are insensitive to the drug alpha amanitin at concentrations up to 1 mg/ml. Transcription results in the generation of several stable variant-specific mRNAs. These mRNAs most likely belong to a family of repetitive expression-site-associated genes. PMID- 3352607 TI - The length of the downstream exon and the substitution of specific sequences affect pre-mRNA splicing in vitro. AB - We have shown previously that truncation of the human beta-globin pre-mRNA in the second exon, 14 nucleotides downstream from the 3' splice site, leads to inhibition of splicing but not cleavage at the 5' splice site. We now show that several nonglobin sequences substituted at this site can restore splicing and that the efficiency of splicing depends on the length of the second (downstream) exon and not a specific sequence. Deletions in the first exon have no effect on the efficiency of in vitro splicing. Surprisingly, an intron fragment from the 5' region of the human or rabbit beta-globin intron 2, when placed 14 nucleotides downstream from the 3' splice site, inhibited all the steps in splicing beginning with cleavage at the 5' splice site. This result suggests that the intron 2 fragment carries a "poison" sequence that can inhibit the splicing of an upstream intron. PMID- 3352608 TI - The cell-specific elastase I enhancer comprises two domains. AB - Two separate domains within the 134-base-pair rat elastase I enhancer and a third domain at the enhancer-promoter boundary are required for selective expression in pancreatic acinar cells. The domains were detected by a series of 10-base-pair substitution mutations across the elastase I gene regulatory region from positions -200 to -61. The effect of each mutant on the pancreas-specific expression of a linked chloramphenicol acetyltransferase gene was assayed by transfection into pancreatic 266-6 acinar cells and control NIH/3T3 cells. The two enhancer domains are nonredundant, because mutations in either eliminated (greater than 100-fold reduction) expression in 266-6 cells. DNase I protection studies of the elastase I enhancer-promoter region with partially purified nuclear extracts from pancreatic tissue and 266-6 cells revealed nine discrete protected regions (footprints) on both DNA strands. One of three footprints that lie within the two functional domains of the enhancer contained a sequence, conserved among several pancreas-specific genes, which when mutated decreased linked chloramphenicol acetyltransferase expression up to 170-fold in 266-6 cells. This footprint may represent a binding site for one or more pancreas specific regulatory proteins. PMID- 3352609 TI - Generation of a mutant form of protein synthesis initiation factor eIF-2 lacking the site of phosphorylation by eIF-2 kinases. AB - The phosphorylation of the alpha-subunit of initiation factor eIF-2 leads to an inhibition of protein synthesis in mammalian cells. We have performed site directed mutagenesis on a cDNA encoding the alpha-subunit of human eIF-2 and have replaced the candidate sites of phosphorylation, Ser-48 and Ser-51, with alanines. The cDNAs were expressed in vitro by SP6 polymerase transcription and rabbit reticulocyte lysate translation, and the radiolabeled protein products were analyzed by high-resolution two-dimensional gel electrophoresis. The wild type and Ser-48 mutant proteins became extensively phosphorylated by eIF-2 kinases present in the reticulocyte lysate, and when additional heme-controlled repressor or double-stranded RNA-activated kinase was present, phosphorylation of the proteins was enhanced. The Ser-51 mutant showed little covalent modification by the endogenous enzymes and showed no increase in the acidic variant with additional eIF-2 kinases, thereby suggesting that Ser-51 is the site of phosphorylation leading to repression of protein synthesis. PMID- 3352611 TI - [Integration and evaluation of a standardized, multi-axis diagnostic system in pediatric psychosomatic medicine]. AB - We present outcome data of 171 children with psychosomatic and child-psychiatric disorders and discuss the pros and cons of two standardized multiaxial diagnostic systems (DSM III and the Multiaxial System of Rutter 1975). Results and arguments were considered until a clearcut choice fell for the DSM-III. As a major conclusion we introduce the BAT-Index, a factor derived by comparing the psychosocial stressors (Axis 4 DSM III) to the highest level to adaptive functioning past year (Axis 5 DSM III) which can be helpful in estimating the to be expected changes and complications in therapeutic settings and gives us a good prognostic assessment of the patient. PMID- 3352610 TI - Localization of a highly divergent mammalian testicular alpha tubulin that is not detectable in brain. AB - Sequence analysis of a mouse testicular alpha-tubulin partial cDNA, pRD alpha TT1, reveals an isotype that differs from both the somatic and the predominant testicular alpha tubulins at approximately 30% of the 212 amino acid residues determined. Although this mouse testicular cDNA retains the highly conserved sequence, Glu-Gly-Glu-Glu, found in the carboxyl termini of many alpha tubulins, the protein extends substantially beyond this sequence and does not terminate with a C-terminal tyrosine. Using rabbit antiserum prepared to a novel synthetic peptide predicted from this mouse testis alpha-tubulin cDNA, we have have detected by immunoblot and indirect immunofluorescence an antigenic epitope present in testicular alpha tubulin that is not detectable in brain alpha tubulins. We find that the antiserum specifically binds to the manchettes and meiotic spindles of the mouse testis but not with neural fibers or tubulin extracts of the adult mouse brain. These results demonstrate that at least one of the multiple alpha-tubulin isotypes of the mammalian testis is expressed and used in male germ cells but not in the brain. PMID- 3352612 TI - [Systemic humoral immune response to food antigens following oral immunization or immunization via the respiratory tract]. AB - Differences and similarities of the systemic humoral immune response to cow's milk proteins were investigated after exposure of the gut or of the airways to antigen, both in children and in rabbits. Circulating antibodies were determined by radioimmunoassay (children and rabbits) and by enzyme-linked immunosorbent assay in a small number of children. An age-dependent reference range was established, reflecting the rapid change of active antibody formation after oral immunization against bovine serum albumin in healthy, non-breastfed children up to the age of 24 months (n = 181). In contrast 16 children with recurrent aspiration due to anatomical disturbances or swallowing difficulties, all had antibody-titers well above this reference range. 7 of 9 children with cow's milk protein intolerance and with failure to thrive (oral immunization) also showed high concentrations of milk antibodies in the circulation. In adult rabbits immunized by oral or inhalational route, the vigorous immune response seen in recurrent aspiration could be mimicked. As investigated by enzyme-linked immunosorbent assay, higher titers of antibodies to bovine serum albumin, alpha lactalbumin, beta-lactoglobulin, alpha-casein and bovine gammaglobulin could be shown in all isotypes tested (specific anti-IgG, -IgA, and -IgE) both in recurrent aspiration (n = 11) and cow's milk protein intolerance (n = 4) as compared to normal age-matched children (n = 14). PMID- 3352614 TI - [Congestive heart failure in a newborn infant with arteriovenous malformation of the vein of Galen: diagnosis using color-coded Doppler image echography]. AB - Arteriovenous malformations of the vein of Galen are rare disorders that may appear in the newborn period with severe congestive heart failure mimicking many intrinsic cardiac defects. Using combined two-dimensional ultrasound and color coded blood flow mapping arterio-venous aneurysm of the vein of Galen and congenital atrial septal defect could be diagnosed in an newborn with congestive heart failure. In addition to the presented clinical value of the new two dimensional color Doppler echography physiological aspects of intracranial arteriovenous fistula in infancy discussed. PMID- 3352615 TI - [Recommendations for operating safety and functional capacity of infant incubators currently in use]. PMID- 3352616 TI - [The course of treated and untreated depressions and anxiety disorders. A clinico psychiatric and epidemiological follow-up study]. PMID- 3352613 TI - [Toxic shock syndrome in 2 girls with pharyngeal infection and wound infection]. AB - In 1981, a 13 year old girl died of her shock lung. She had been admitted with the classical toxic shock syndrome then still unknown to us. Staphylococcus aureus had been cultured from a pharyngeal swab. But even in 1987, it took us 48 hours to correctly diagnose the toxic shock syndrome in a 17 year old girl. The diagnosis became evident when she was found to have a staphylococcus aureus wound infection after a surgical procedure. For pediatricians, it is crucial to know this syndrome well. Not only menstruating girls using tampons, but also quite young children can acquire this disease. Quick diagnosis and prompt institution of the correct therapy can be life saving. PMID- 3352617 TI - [Electron microscope studies in functioning pigmented ("black") adenoma of the adrenal gland]. PMID- 3352618 TI - [Preparation and possibilities of the use of immuno-gold conjugate in light- and electron microscopic immunohistochemistry]. PMID- 3352620 TI - [Vascular structure of colonic diverticula]. PMID- 3352619 TI - [Lectin-histochemical studies in osteoclastoma and other giant cell processes]. PMID- 3352621 TI - [Actinomycosis of the liver in wearers of IUDs]. PMID- 3352622 TI - [Immunohistochemical and ultrastructural studies in chordoma]. PMID- 3352623 TI - Chromosomal analysis in mouse eggs fertilized in vitro with sperm exposed to ultraviolet light (UV) and methyl and ethyl methanesulfonate (MMS and EMS). AB - Chromosome aberrations were analyzed at the first-cleavage metaphase of mouse eggs fertilized in vitro with sperm exposed to ultraviolet light (UV) as well as to methyl and ethyl methanesulfonate (MMS and EMS). The frequencies of chromosome aberrations markedly increased with dose of UV as well as with concentration of MMS and EMS. In the UV-irradiation group, the frequency of chromosome-type aberrations was much higher than that of chromatid-type aberrations. About 90% of chromosome aberrations observed in the eggs following MMS and EMS treatment to sperm were chromosome type in which the frequency of chromosome fragments was the highest. The effects of UV on the induction of chromosome aberrations were clearly potentiated by post-treatment incubation of fertilized eggs in the presence of Ara-C or caffeine, but the effects of MMS and EMS were not pronounced by post-treatment of Ara-C or caffeine. The results indicate a possibility that UV damage induced in mouse sperm DNA is reparable in the eggs during the period between the entry of sperm into the egg cytoplasm and the first-cleavage metaphase. PMID- 3352624 TI - Analysis of mouse metaphase II oocytes as an assay for chemically induced aneuploidy. AB - Our initial objective was to develop an in vivo mammalian, female aneuploid assay that is consistent, time efficient, and that yields a large number of oocytes amenable to objective analyses. Subsequently, we desired to use such an assay for identifying chemicals and dosages that could increase the incidence of aneuploidy in mouse metaphase II oocytes. The experimental protocol involved superovulating CD-1 mice with PMS; HCG was given 48 h later. At the time of HCG injection, different dosages od diethylstilbestrol diphosphate, cadmium chloride, chloral hydrate, or colchicine were injected intraperitoneally. 17 h later, oocytes were collected and fixed prior to C-banding the chromosomes. The procedure required about 3 h to process oocytes from 25 mice and yielded over 100 analyzable metaphase II oocytes. Colchicine was the only compound tested that resulted in a statistically significant (P less than 0.01) increase in hyperploid (N greater than 20) oocytes over controls. The incidence of hyperploid oocytes in the colchicine group was 2/167, 1/182, 21/220, and 38/202, for control, 0.1 mg/kg, 0.2 mg/kg, and 0.3 mg/kg, respectively. This assay appears sensitive for aneuploidy detection but requires further validation. PMID- 3352625 TI - Inactivation of DNA-mediated transformation of hamster cells by gamma-rays and deoxyribonuclease I. AB - DNA damage has been induced in the mammalian expression vector pSV2-gpt by irradiation with X-rays or treatment with deoxyribonuclease I (DNAase I) under controlled conditions in vitro. The biological effect of such treatment was assessed by stable gene expression in Chinese hamster ovary (CHO) cells using DNA mediated gene transfer. Induction of DNA double-strand breaks (dsbs), resulting from the interaction of independently-induced single-strand breaks (ssbs) under the present conditions, was measured by agarose gel electrophoresis of the treated vector. The correlation between radiation-induced gene inactivation and dsb induction mediated by OH radicals suggests that a dsb in the gene is a major inactivating lesion in this system. Individual radiation-induced ssbs and nucleotide damage are produced much more frequently than dsbs under these conditions, but the majority of these lesions do not appear to inactivate the gpt gene. DNAase I treatment, giving only simple 5' P + 3' OH breaks in the vector DNA, gave a correlation of approximately 1.5 dsb in the gpt gene per inactivating event, confirming little repair of dsbs in this system. Inactivation of the gpt gene without appreciable formation of dsbs was found, however, when the vector was irradiated at high dose rate in the presence of the OH-radical scavenger KBr. The nature of non-break damage causing inactivation requires further study. PMID- 3352626 TI - Distribution of O6-ethylguanine in DNA exposed to ethylnitrosourea in vitro as visualized by electron microscopy using a monoclonal antibody. AB - Application of a monoclonal antibody (Mab ER-6; Rajewsky et al., 1980) specific for O6-ethyl-2'-deoxyguanosine (O6-EtdGuo), in conjunction with a protein-free spreading procedure for double-stranded DNA molecules and transmission electron microscopy, permits the visualization of antibody molecules complexed to O6 EtdGuo residues formed in DNA upon reaction with the carcinogen N-ethyl-N nitrosourea (EtNU) (Nehls et al., 1984). To obtain information on the distribution of O6-EtdGuo in native DNA exposed to EtNU in vitro, samples of purified rat brain DNA were briefly incubated with EtNU at concentrations differing by a factor of 8 (0.5 and 4 mg of EtNU/ml, respectively). As determined in DNA hydrolysates by competitive radioimmunoassay, the resulting DNA preparations contained O6-EtdGuo at O6-EtdGuo/2'-deoxyguanosine molar ratios of 15.1 X 10(-5) and 116 X 10(-5), respectively. Interspace distances between Mab binding sites in both sets of ethylated DNA were determined by electron microscopy both in individual DNA fragments of different size, and in computer generated, long-thread DNA constructs. Comparative statistical analyses by a newly developed MOLRANDO computer program show a non-random distribution pattern of Mab-binding O6-EtdGuo residues. PMID- 3352627 TI - Transmission of radiation-induced rearrangements through cell divisions. AB - A BrdU incorporation technique associated with heat denaturation, acridine orange staining and UV irradiation, was applied to G0-irradiated lymphocyte cultures. This made it possible both to obtain an R-banding, and to estimate the number of divisions undergone by each cell in mitosis irradiation. Cell survival and slowing down of the cell cycle could be distinguished. The frequency of various types of rearrangements, and their association was studied at each cell division. It is shown that the loss of cells carrying chromosomal rearrangements is determined by several parameters such as the presence of dicentric or multicentric chromosomes and above all the association of several rearrangements in the same cell. PMID- 3352628 TI - Lymphocytes proliferation kinetics and SCE variation after rubella vaccination. AB - The effect of anti-rubella vaccination on lymphocyte proliferation kinetics in vitro and on SCE frequency was studied in three young women. The studies were carried out by taking blood samples before vaccination (day 0) and subsequently on days 7, 14, 28 and 42. The mitotic index (MI) shows a decrease at day 14 and 28 followed at day 42 by an increase above day 0 levels. The average cell cycle (ACC) shows a decrease at day 14 followed by an increase at day 28. Complex variations were also found in the percentage distribution of cells in the various division classes. The SCE frequency showed variations inverse to the MI. The whole picture seems to indicate the existence of changes in the lymphocyte population which can be correlated with immune response. PMID- 3352629 TI - The biological activity of hydrogen peroxide. IV. Enhancement of its clastogenic actions by coadministration of L-histidine. AB - An enhancing effect of L-histidine (L-His) was detected on the induction by hydrogen peroxide (H2O2) of chromosomal aberrations of both the chromosome type and the chromatid type, in human embryonic fibroblasts. The maximum efficiency of induction was about 8-fold higher in the presence of L-His than in the presence of H2O2 alone, at a concentration of L-His of 50 microM. D-His and DL-His showed lower enhancing effects than L-His, with approximately 2-fold and 5-fold enhancement of induction of chromosomal aberrations, respectively. L-Histidinol and L-His-methyl ester, among various derivatives of L-His tested, also enhanced this process. However, the effects of these derivatives were smaller than those of L-His in a range of concentrations equivalent to that of the most effective dose of L-His (50 microM), while they produced greater enhancement than L-His at concentrations higher than 200 microM. Other derivatives of L-His, such as L carnosine, urocanic acid, imidazolepyruvic acid, 1-methyl-L-His, imidazolelactic acid, imidazoleacetic acid and histamine and imidazole itself did not enhance the frequency of chromosomal aberrations induced by H2O2. These results indicate that at least both the imidazole ring and the amino group are essential components of the chemical structure of L-His required for the enhancing effect. Moreover, in order to cause such an enhancing effect, L-His had to be applied together with H2O2 to cells, because the enhancing effect of L-His was not observed with cells which were washed after pretreatment with L-His. The preliminary study suggested that this enhancing effect depends on the His-peroxide adduct derived from L-His and H2O2. None of the amino acids tested other than His produced any enhancing effect on the induction of chromosomal aberrations by H2O2. PMID- 3352630 TI - Lower prevalence of chromosome aberrations and SCEs in self-poisoned pregnant women. AB - A cytogenetic investigation was conducted in 18 self-poisoned pregnant and 16 self-poisoned non-pregnant women and in 31 pregnant and non-pregnant controls. Blood samples for analysis of chromosomal aberrations and SCEs were collected from women who were at different early stages of pregnancy. The difference between self-poisoned women and controls was very highly significant in the case of chromatid-type and unstable chromosome-type aberrations and highly significant in the case of SCEs. Further, the frequency of chromatid aberrations in pregnant women relative to non-pregnant ones was significantly lower suggesting a possible protective effect of pregnancy. PMID- 3352631 TI - Ultraviolet radiation-induced lethality and repair of pyrimidine dimers in fish embryos. AB - Pimephales promelas (fathead minnow) embryos were used to show a correlation between induction of pyrimidine dimers in DNA and embryo death. Embryo killing was measured by a lack of heart-beat and blood circulation at 48 h post ultraviolet radiation (UVR). When the embryos were exposed to various doses of UVR from a FS-40 sunlamp followed by exposure to photoreactivating light (PRL) (320-400 nm), the number of pyrimidine dimers decreased significantly. The photorepair of dimers was accompanied by a substantial increase in embryo survival. When embryo killing was examined as a function of the number of dimers present, dimers were identified as a major lesion involved in UVR-induced killing in these fish embryos. This in vivo study on photoreactivation treatment of fish embryos shows a direct association between UVR-induced pyrimidine dimers and embryo killing. In addition, when embryos were held in the dark for 9 h after UVR, 50% of the dimers were removed by excision repair. PMID- 3352632 TI - Induction of mutations in males of the fish Oryzias latipes at a specific locus after gamma-irradiation. AB - We have studied frequencies of mutations induced at the b locus of the fish, Medaka Oryzias latipes, after gamma-irradiation. Homozygotes for the b locus have colorless melanophores whose phenotypic expression can be distinguished from that of the wild type. An advantage of the use of oviparous fish for detection of skin color mutations is that the mutant phenotype can be confirmed as early as 1.5 days after fertilization because of the transparent egg membrane of the embryo. Wild-type (B/B) male fish were exposed to 4.75 or 9.5 Gy of 137Cs gamma-rays at a dose rate of 0.95 Gy/min and then mated with the female testers (b/b). A total of 77,761 F1 offspring were examined for mutation and other abnormalities. In the control, we had 1 mutant among 22,068 offspring, resulting in a mutation rate of 4.53 X 10(-5)/locus/gamete. However, this mutant embryo died before hatching. Therefore, in an attempt to present specific-locus mutation frequencies in the fish, the frequencies of color mutants that survived more than 4 days after hatching were used as frequencies of viable mutants; (number of viable color mutants)/(number of hatched fry that survived more than 4 days after hatching). In the 4.75 Gy-irradiated group the viable mutant frequencies were 45.0 X 10(-5), 69.7 X 10(-5) and 0/locus/gamete, while exposure to 9.5 Gy resulted in mutation rates of 217 X 10(-5), 130 X 10(-5) and 8.06 X 10(-5), respectively, for sperm, spermatids and spermatogonia. In comparison with viable color mutant frequencies those of the total color mutants, which include such mutants as ones that died before hatching (defined as number of total color mutants/number of fertilized eggs minus number of early deaths), were considerably higher. For sperm, spermatids, and spermatogonia after exposure to 4.75 Gy, the frequencies were 1180 X 10(-5), 629 X 10(-5) and 9.90 X 10(-5)/locus/gamete, respectively, and in 9.5-Gy-irradiated fish, the frequencies were 1940 X 10(-5), 953 X 10(-5) and 55.5 X 10(-5). Although our data are incomplete, the present results were compared with mutation induction in mice. We concluded that the frequencies of viable color mutants in the fish can be compared with those in mice. PMID- 3352633 TI - Effects of hormone treatment on chromosomal radiosensitivity of somatic and germ cells of Snell's dwarf mice. AB - The X-ray induction of micronuclei and structural chromosomal aberrations was studied in bone-marrow cells of normal and dwarf (dw) mice in combination with thyroxine and/or prolactin treatment or otherwise. Hormone treatment clearly increased micronuclei induction but not chromosome breakage, suggesting that indirect effects were involved. Since no clear differences in the timing of the final stage of erythropoiesis could be found, it is likely that the indirect effects are mediated via the formation-differentiation kinetics of erythroblasts. The induction of reciprocal translocations by X-rays in stem cell spermatogonia of dwarf mice was lower than in normals and treatment with prolactin, growth hormone and/or thyroxin, did not influence the chromosomal radiosensitivity of spermatogonial stem cells. PMID- 3352634 TI - The effect of dose fractionation on the frequency of ethylnitrosourea-induced dominant cataract and recessive specific locus mutations in germ cells of the mouse. AB - A combined dominant cataract-recessive specific locus mutation experiment for fractionated exposure to ethylnitrosourea (2 X 80 mg/kg, 24-h fractionation interval) was designed to determine if lower doses of ethylnitrosourea are more effective in inducing dominant cataract mutations as suggested by previous results. This observation was not confirmed by the present experiment. The extensive, statistically more reliable specific locus results indicate an additive effect of fractionated ethylnitrosourea treatment. A saturable repair system for ethylnitrosourea-induced DNA damage has been previously documented (Karran et al., 1979; Sega et al., 1986; Van Zeeland et al., 1985). Two parameters inherent to a saturable system, the minimal time required for the saturated system to recover and the minimal dose to saturate the system are important, and results of experiments employing a fractionation exposure protocol must be interpreted relative to these two parameters. Longer fractionation intervals or smaller doses result in a reduced mutagenic effect. Due to the inherently lower experimental variability of the specific locus mutation assay as compared to the dominant cataract assay, the specific locus assay is the test of choice to determine factors affecting the mammalian germ cell mutation rate. The dominant cataract test requires a larger investment of experimental resources to achieve a comparable degree of accuracy. The dominant cataract mutation test is important in assessing the mutation rate to dominant alleles in germ cells of mammals. Due to the immediate expression of the mutant phenotype in newly occurring dominant mutations, a dominant mutation assay screens a genetically relevant endpoint in an assessment of the mutagenic hazard for man in mouse experiments. A multi-endpoint design screening specific locus, dominant cataract, and biochemical mutational endpoints (Ehling et al., 1985) allows a systematic comparison of mutagenic results for different classes of mutations in the same animals. PMID- 3352635 TI - Induction of congenital malformation in mice by parental irradiation: transmission to later generations. AB - In order to investigate the genetic basis of the increased incidence of congenital malformations in the offspring of irradiated mice, the frequency of malformations among the offspring of individual F1 sons of irradiated females was studied in detail. Among 90 fully tested F1 sons of females which had been mated 15-21 days after receiving 360 cGy X-rays 4 were definite or probable carriers of dominant genes giving a low penetrance of malformations. This confirms that the malformations seen in the first generation are of genetic origin and can be transmitted to later generations. However, the incidence and penetrance of the mutant genes detected were too low to account for all the anomalies found in the first generation. It was concluded that the genetic basis of the original anomalies was heterogeneous, with some due to genetic changes of high penetrance and rapidly eliminated, and others due to genes of low penetrance like those found in this work. Other malformations, in both the irradiated and control series, were probably of non-genetic origin. PMID- 3352637 TI - Dominant cataract and recessive specific-locus mutations detected in offspring of procarbazine-treated male mice. AB - The induction of dominant cataract mutations by procarbazine was studied concomitantly with the induction of specific-locus mutations in treated male mice. The most effective dose in the specific-locus test, 600 mg/kg of procarbazine, and a fractionated dose of 5 X 200 mg/kg were used. The frequencies of dominant cataract mutations were higher, but not significantly different from the historical control. The ratio between the number of recovered specific-locus and dominant cataract mutations was in accordance with that found in our experiments with gamma-rays (Ehling et al., 1982; Kratochvilova, 1981) or in experiments with ethylnitrosourea (Favor, 1986). A total of 3 dominant cataract mutations were recovered in the offspring of procarbazine-treated spermatogonial stem cells. Two mutations had complete penetrance while the third exhibited a reduced penetrance of approximately 70%. The viability and fertility of the heterozygotes of all 3 mutations were not affected. Only 1 mutation was shown to be viable as a homozygote. PMID- 3352636 TI - Genetic injury in hybrid male mice exposed to low doses of 60Co gamma-rays or fission neutrons. III. Frequencies of abnormal sperm and reciprocal translocations measured during and following long-term weekly exposures. AB - Male B6CF1 mice were exposed to either fission neutrons or 60Co gamma-rays at once-weekly doses approaching occupational levels for periods up to 60 weeks. Both during and after the irradiation sequence, the mice were screened to determine the incidence of abnormal epididymal sperm and of reciprocal chromosome translocations in metaphase spermatocytes. Abnormal sperm frequencies equilibrated with dose/week by 10 weeks and also showed an additive nonlinear seasonal increment. The relative biological effectiveness (RBE) for these damages is 12 +/- 1. After exposures ended, sperm frequencies in gamma-irradiated mice quickly returned to near-normal levels. Neutron-irradiated males showed a significantly elevated level of abnormalities for approximately 30 weeks--a paradoxical finding--as no clear evidence of cumulative injury was seen during exposure. When assayed at 10 and 25 weeks of exposure but not later, translocation frequencies demonstrated an increment, significant in the neutron series, attributed to irradiated spermatocytes. Dose-response analysis with cumulative dose up to the 60-week maximum gave an RBE of 45 +/- 10. Post exposure, the incidence of translocations subsided slightly, but the RBE remained above 30. PMID- 3352639 TI - X-ray- and chemically induced germ-line mutation causing phenotypical anomalies in mice. AB - A large and significant increase of phenotypical anomalies was observed in the progeny of ICR parent mice treated before mating with X-rays, urethane, 7,12 dimethylbenz[a]anthracene, ethylnitrosourea (ENU), and 4-nitroquinoline 1-oxide, but the increase was not significant with furylfuramide. Major types of induced anomalies were cleft palate, dwarf, open eyelid, tail anomalies, and exencephalus. Dwarf, open eyelid and tail anomalies were predominant types of viable anomalies and were inherited as if they were dominant mutations with varying expressivity or penetrance. Incidence of prenatal anomalies increased with treated doses of X-rays, urethan, or ENU for both spermatozoa and spermatogonia. Spermatogonia were less sensitive to X-rays and urethane than spermatozoa, while ENU induced a very high incidence of prenatal anomalies by the spermatogonial treatment. In contrast to the previous works with X-rays, there was a clear, almost linear increase of anomalies in the dose range from 0 to 216 rad after spermatogonial exposure. For treatment of oocytes, there was also a clear increase with doses of X-rays and urethane. Doubling doses of X-rays for prenatal anomalies were 12 rad for spermatozoa, 27 rad for spermatogonia, and 19 rad for mature oocytes. These values are similar to those for ordinary mouse mutations. However, the mean rate of prenatal anomalies per rad (1.2 X 10(-4), 6.6 X 10(-5) and 9.1 X 10(-5) for spermatozoa, spermatogonia and mature oocytes, respectively) and that for 1 micrograms/g of ENU (3.4 X 10(-4) for spermatogonia) were 4-40 times higher than that of ordinary mutation in mice, because overall phenotypical abnormalities were scored in this study. Information obtained from the work on phenotypical anomalies is valuable to assess genetic risk of radiation and chemicals, because a majority of human genetic diseases show this kind of irregular and uncertain inheritance and most of the induced anomalies are similar to those found in humans. PMID- 3352638 TI - Effect of X-ray and ethylnitrosourea exposures separated by 24 h on specific locus mutation frequency in mouse stem-cell spermatogonia. AB - Specific-locus mutation frequencies in mouse stem-cell spermatogonia were determined in 3 experiments in which mature male mice were exposed to 100,m 300, or 500 R of X-rays followed, 24 h later, by intraperitoneal injection of 100 mg/kg of ethylnitrosourea (ENU). The purpose was to find out if the mutation frequencies would be augmented over those expected on the basis of additivity of the effects of the separate treatments. Such augmentation had been observed in earlier work in which exposure to 100 or 500 R of X-rays was followed 24 h later by a second exposure of 500 R. No augmentation was observed for X-rays followed by ENU. The mutation frequencies in all 3 experiments actually fell below those expected on the basis of additivity, although the reductions were not statistically significant. PMID- 3352640 TI - Influence of dietary carrot on cytostatic drug activity of cyclophosphamide and its main directly acting metabolite: induction of sister-chromatid exchanges in normal human lymphocytes, Chinese hamster ovary cells, and their DNA repair deficient cell lines. AB - We have utilized an in vivo drug metabolism technique (i.e. injecting the chemical into rat and isolating plasma with metabolites from blood) for detecting the genotoxicity of indirectly acting cyclophosphamide and its directly acting metabolite phosphoramide mustard in cultures of human peripheral blood lymphocytes of normal individuals, Fanconi's anaemia (FA) and aplastic anaemia (AA) patients, wild-type Chinese hamster ovary cells (CHO) and its DNA repair deficient mutant 43-3B cells. In addition, the influence of dietary carrot on the clastogenic activity of these 2 chemicals in all the different cell types was studied. The genotoxicity was assessed by the ability of the metabolites of these agents to induce sister-chromatid exchanges in the treated cells. A dose dependent increase in the frequencies of sister-chromatid exchanges was observed in all cell strains following treatment with activated metabolites of cyclophosphamide or phosphoramide mustard. The sensitivity of lymphocytes from normal donors, FA and AA patients to these 2 chemicals was similar. In CHO cell lines the induced frequency of sister-chromatid exchanges was slightly higher after treatment with the metabolites of cyclophosphamide than with phosphoramide mustard. The mutant 43-3B cells responded with higher frequencies of SCEs when compared to the wild-type CHO cells, about 1.5-2-fold, at low doses. Pretreating of rats with fresh carrot juice effectively inhibited the increase in the frequencies of sister-chromatid exchanges induced by cyclophosphamide in wild type and mutant CHO cells (P less than 0.01), and to a lesser extent in human lymphocytes (p less than 0.05). In contrast, no inhibitory effect was observed in any of these cell types in combination of dietary carrot for direct acting phosphoramide mustard on the frequency of induced sister-chromatid exchanges. The possibility that dietary carrot exerts its antimutagenic effect by affecting the processes of enzymatic activation of cyclophosphamide is discussed. PMID- 3352642 TI - Activity of germ-cell mutagens and nonmutagens in the rat spermatocyte UDS assay. AB - The ability of 13 chemicals of known germ-cell mutagenicity to induce unscheduled DNA synthesis (UDS) in rat spermatocytes was examined. At selected times following i.p. injection of test compounds, spermatocytes were isolated from Fischer 344 rats by enzymatic digestion of the seminiferous tubules and cultured for 24 h in the presence of [3H]thymidine. 7 compounds, methyl methanesulfonate, triethylenemelamine, cyclophosphamide, methylnitrosourea, ethylnitrosourea, procarbazine, and dibromochloropropane produced positive UDS responses in spermatocytes. These chemicals are also positive for specific locus mutations, heritable translocations, or dominant lethal mutations when administered to male rodents. Mitomycin C, which produces DNA interstrand crosslinks and induces heritable mutations and translocations in male germ cells, failed to stimulate UDS in rat spermatocytes. Germ-cell nonmutagens N-methyl-N'-nitro-N nitrosoguanidine, dimethylnitrosamine, 4-nitroquinoline 1-oxide, and ethylene dibromide were negative in the rat spermatocyte UDS assay. Correlation of these results with those of other assays for heritable mutations in germ cells indicates that the in vivo/in vitro spermatocyte DNA repair assay is useful in predicting the mutagenic potential of chemicals in male germ cells. PMID- 3352641 TI - Genotoxic effects of a sub-acute low-level inhalation exposure to a mixture of carcinogenic chemicals. AB - A study was conducted using a combined testing protocol (CTP), to determine whether short-term biological end-points, singly or in combination, are sufficiently sensitive to identify damage induced by exposure to ambient levels of industrial chemicals. A small-scale inhalation set-up which is both economical and easy to assemble was designed. Mice were exposed to 4 concentrations of a custom-blend mixture of benzene, chloroprene, epichlorohydrin and xylene in a ratio of 2:2:1:2, respectively. The concentrations for benzene, chloroprene and xylene were 0, 0.1, 1.0 and 10 ppm each. Concentrations for epichlorohydrin were half those for the other components. Groups of 22 males and 22 female mice were exposed to each concentration of the mixture for 3 and 6 weeks. Selected biological end-points including urine mutagenesis, bone marrow cell aberrations and micronuclei, spleen lymphocyte aberrations and liver enzyme induction were monitored. The spleen lymphocyte aberrations and liver enzyme induction were the most sensitive end-points. The lymphocytes showed a significant induction of chromosome aberrations from exposure for 3 weeks to all 3 concentrations of the mixtures. After 6 weeks of exposure, significant induction of aberrations was observed after exposure to low and medium concentrations but not to the high concentration. This lack of response at the high concentration after 6 weeks exposure, appeared to correlate with a significant induction of glutathione S transferase in the liver. Since this enzyme is known to detoxify 3 of the 4 chemicals in our mixture, it may indicate a detoxification mechanism after enzyme induction. The present study indicates that the CTP is sufficiently sensitive to identify toxicological effects after exposure to ambient levels of a gas mixture. PMID- 3352643 TI - Effect of dipyridoimidazole pretreatment on mutagen activation in rats. AB - Rats were pretreated with a single oral dose of different mutagenic fractions obtained from glutamic acid pyrolysate: Glu-P-2 (2-amino-dipyrido[1,2-a:3',2' d]imidazole), Glu-P-3 (3-amino-4,6-dimethyldipyrido[1,2-a:3',2'-d]imidazole), the tar residue and a basic extract (B2). The liver S9 fractions of these animals were used to investigate the mutagenic activation of 3 promutagens (2 aminoanthracene, Glu-P-2 and Glu-P-3) in Salmonella typhimurium strain TA1538. Different factors were analyzed; influence of the structure of the compounds administered, doses, time interval between pretreatment and sacrifice and sex of the rats. Interpretation of the hepatic induction effects was complicated, however, by the fact that simple oral pretreatment with the solvents (DMSO or ethanol) enhances the activation of the substrates tested for mutagenicity. A dose-effect relationship was found between 2-AA mutagenic activation and Glu-P-2 pretreatment. Glu-P-3 induced the activation of 2-AA more than did Glu-P-2, in the male as in the female. The mutagenicity of 2-AA activated with S9 from male rats was found to be optimal after 24 h pretreatment with 20 mg Glu-P-2/kg b.w. The mutagenicity of Glu-P-2 was poorly influenced by the different pretreatments applied to either the males or the females, whereas some dose effect was found in the autoinduction of Glu-P-2 mutagenicity. Compared to Glu-P-2, the mutagenicity of Glu-P-3 was increased at higher levels when tested with S9 from males pretreated with the same compound, but no differences were observed between males and females. PMID- 3352644 TI - Effect of anticonvulsants on human chromosomes. 2. In vitro studies. AB - The effects of 3 anticonvulsant drugs (diphenylhydantoin, ethosuximide, and phenobarbital) on human peripheral lymphocytes in vitro were studied. The rate of chromosomal aberrations induced by the 3 anticonvulsants was significantly increased from the first concentration analyzed, similar to half the therapeutic serum concentration. These findings are compared with other previous reports. PMID- 3352645 TI - Chromosomal damage induced by maleic hydrazide in mammalian cells in vitro and in vivo. AB - The induction of sister-chromatid exchanges (SCE) and chromosomal aberrations (Ch.Ab.) by the herbicide maleic hydrazide (MH) has been investigated in Chinese hamster ovary (CHO) cells grown in vitro and in bone marrow cells of mice treated in vivo. MH induces SCE and Ch.Ab. in CHO cells without metabolic activation; however, no induction of SCE was found in the in vivo experiments. PMID- 3352646 TI - SCE induction in Chinese hamster ovary cells (CHO) exposed to G agents. AB - Cultured Chinese hamster ovary (CHO) cells were exposed to two neurotoxic organophosphates, either sarin (GBI, GBII) at 1.4 X 10(-3) M or soman (GD) at 1.1 and 2.2 X 10(-3) M for 1 h, grown and their metaphase chromosomes scored for sister-chromatid exchanges (SCE). No cytotoxicity was seen with either agent at any dose level tested. Since histograms of SCE per cell showed that they were non symmetrically arrayed around the mean, the number of SCEs were analyzed by using the nonparametric tests, Mann-Whitney and Kruskall-Wallis. Agents GBI and GBII did not show any significant increase in SCE over baseline. On the other hand, GD demonstrated a statistically significant increase in SCE with and without metabolic activation. Ethyl methanesulfonate (EMS) alone at 5 X 10(-3) M and cyclophosphamide (CP) at 10(-4) M in the presence of rat microsomes (S9) induced a 3- and 8-fold increase in SCE per cell, respectively. PMID- 3352647 TI - Mutagenic and clastogenic activity of nitracrine analogues in cultured V79 Chinese hamster cells. AB - Nitracrine is used clinically as an antitumour agent, and analogues are actively being developed in some laboratories. The mutagenic activity of 9-[(3 dimethylaminopropyl)amino]-acridine and its 1-nitro (nitracrine), 2-, 3- and 4 nitro derivatives was evaluated at the 6-thioguanine and ouabain resistance loci in cultured Chinese hamster fibroblasts (V79-171b cell line). The des-nitro, 2- and 3-nitro caused no statistically significant mutagenic activity at either locus. Each of these 3 compounds weakly increased (approximately 2-fold) the incidence of micronuclei in the same cell line when tested at cytotoxic doses. Both the 1- and 4-nitro compounds increased the incidence of 6-thioguanine resistant cells from around 1 in 10(-6) to approximately 1 in 10(-4). The former compound significantly increased the frequency of ouabain-resistant cells. Both of these compounds were potent inducers of micronuclei in V79-171b cells, indicating high clastogenic activity. It would appear prudent to regard both of these compounds as potential human carcinogens. PMID- 3352648 TI - Nitroso-aldicarb induces sister-chromatid exchanges in human lymphocytes in vitro. AB - Nitroso-aldicarb was tested for its ability to induce sister-chromatid exchanges (SCE) and cell-cycle delay in human peripheral blood lymphocytes in vitro. This derivative of aldicarb induced a dose-dependent increase in SCE values per cell. In addition, a slight decrease in the successive mitotic progression of cells in culture was observed. PMID- 3352649 TI - Genotoxicity of epoxy resin hardeners in the hepatocyte primary culture/DNA repair test. AB - The genotoxicity of 9 chemicals used as epoxy resin hardeners was examined in the DNA repair test with rat hepatocytes. DNA repair synthesis was elicited by 7 chemicals, i.e., 4-aminodiphenyl ether, 4,4-diaminodiphenyl ether, 3,4,4' triaminodiphenyl ether, 3,3'-dichloro-4,4'-diaminodiphenyl ether, 1,3-phenylenedi 4-aminophenyl ether, 4,4'-diaminodiphenyl methane and 4,4'-methylene-bis(2 chloroaniline). The positive results obtained with 4 epoxy resin hardeners of unknown carcinogenicity, i.e., 4-amino-diphenyl ether, 3,4,4'-triaminodiphenyl ether, 3,3'-dichloro-4,4'-diaminodiphenyl ether and 1,3-phenylene-di-4 aminophenyl ether suggest that they may be carcinogens. The genotoxicity of 1,4 phenylene-di-4-aminophenyl ether, of unknown carcinogenicity, and 4,4' diaminodiphenyl sulfone, for which there is no sound proof of carcinogenicity, was not confirmed in the DNA repair test. The result with 4,4'-diaminodiphenyl sulfone was in agreement with its lack of mutagenicity in Salmonella typhimurium. PMID- 3352651 TI - In vivo genotoxicity of nitrates and nitrites in germ cells of male mice. II. Unscheduled DNA synthesis and sperm abnormality after treatment of spermatids. AB - Effects of both sodium nitrate (doses of 600 and 1200 mg/kg/day for 3 days) and sodium nitrite (doses of 60 and 120 mg/kg/day for 3 days) on spermatids of mice were investigated by measuring unscheduled DNA synthesis (UDS) 17 days after the end of treatment, and sperm-head abnormality 11 and 17 days after the end of treatment. Neither chemical induced the UDS response in early to mid spermatids (17 days). The only positive result in the sperm-head abnormality test was obtained for the dose of 120 mg/kg/day of sodium nitrite both at 11 and 17 days after treatment. The results presented are in accordance with those of our earlier experiments with the same chemicals, suggesting their nonmutagenic action on the tested germ-cell stages of male mice. PMID- 3352652 TI - Mutagenic effects of dimethyl terephthalate on mouse somatic cells in vivo. AB - The mutagenic activity of dimethyl terephthalate (DMtP) was evaluated in the micronucleus test in mice. A clear clastogenic effect was obtained at all concentrations studied (0.2-1.0 mmole/kg body weight). The maximum number of micronuclei occurred 24 h after a single intraperitoneal (i.p.) injection. The time-course for the DMtP-induced micronuclei was in agreement with the available data on the rapid excretion of phthalates from the mammalian body. The dose effect response was best described by a linear equation with a logarithmic component. The emergence of the latter term was related to the toxic effects of DMtP at higher concentrations on bone marrow erythropoietic function. A comparison of the effects induced by DMtP and by methyl nitrosourea indicated that DMtP cannot be considered a strong mutagenic compound. We have compared the sensitivity of the mouse micronucleus test and that of Drosophila dominant-lethal test by contrasting the effects obtained at similar exposure doses. This comparison leads to the conclusion that the micronucleus test is capable of responding to far lower phthalate concentrations than the Drosophila dominant lethal mutation test. Our results testify to the ability of dimethyl terephthalate to cause genotoxic damages in vivo in both somatic and germinal cells of higher organisms. Thus, the chemical in question may be of potential genetic hazard to man. PMID- 3352650 TI - In vivo genotoxicity of nitrates and nitrites in germ cells of male mice. I. Evidence for gonadal exposure and lack of heritable effects. AB - Effects of nitrate (doses of 600 and 1200 mg/kg/day during 14 days) and sodium nitrite (60 and 120 mg/kg/day during 14 days) on germ cells of male mice were investigated. The mode of application was stomach intubation. The germ cell stages analysed were spermatids (for the heritable effects) and differentiating and stem-cell spermatogonia (for direct effects). A lack of heritable translocations, sperm abnormalities, as well as morphological changes, such as changes in eyes, coat colour, testes and body weight, was demonstrated in F1 males originating from treated P males. Significant effects in treated males were found with respect to: (1) sex-chromosomal univalency in the diakinesis methaphase I stage after the treatment of stem spermatogonia (both doses of sodium nitrate and the higher dose of sodium nitrite), (2) sperm-head abnormalities after treatment of differentiating spermatogonia (the higher dose of sodium nitrate and both doses of sodium nitrite), and (3) fertility after treatment of spermatids (the higher dose of sodium nitrite). Nonmutagenic effects and possible carcinogenic potential of the tested doses are discussed. PMID- 3352653 TI - SCE increases after an accidental acute inhalation exposure to EtO and recovery to normal after 2 years. AB - Sister-chromatid exchanges (SCEs) were studied in 3 workers accidentally exposed for about half an hour to high levels of ethylene oxide (more than 700 ppm) during a sterilizing process. The 3 workers had clinical symptoms of exposure and were tested for SCE frequencies 5 days and 2 years after the accident: 2 had also been tested 6 months earlier. All 3 showed a similar increase in SCEs after the accident, to a mean of 13.8 SCEs/cell compared with 8.6 for a control group. The incidence of 'high-frequency cells' was markedly elevated but decreased over 2 years, when the mean SCE frequencies had also returned to pre-accident levels. PMID- 3352654 TI - Differential response of the dog quadriceps muscle to external skeletal fixation of the knee. AB - The change in muscle fiber size and fiber percentage was studied in three heads of the dog quadriceps following 10 weeks of immobilization using an external skeletal fixator. Muscle biopsy morphometric analysis revealed that muscle fiber atrophy was greatest for the vastus medialis and least for the rectus femoris. The atrophic response for type 1 fibers was, in order from most to least atrophied: VM greater than VL greater than RF, whereas for type 2 fibers the corresponding order was VM = VL greater than RF. An increase in connective tissue was also observed for all muscles. These results are discussed in terms of skeletal muscle architecture, initial fiber-type distribution, and level of use. As a result, predictions are made as to the muscles that are most vulnerable to disuse atrophy, namely the postural muscles that contain a relatively large proportion of slow muscle fibers and cross a single joint. Conversely, those that are least susceptible to atrophy are those that are not used as postural muscles, that cross multiple joints, and that are predominantly composed of fast muscle fibers. PMID- 3352655 TI - Transient weakness and altered membrane characteristic in recessive generalized myotonia (Becker). AB - The isometric force of arm and leg muscles was studied in five unrelated patients with recessive generalized myotonia (Becker). The symptom of myotonia was present mainly in the legs, whereas transient weakness was the prominent symptom in the arms. Tocainide improved both symptoms, although it improved the stiffness more than the weakness. A specimen of intact muscle fibers was excised from the external intercostal muscle of one of the patients. The resting potential of the fibers was normal, but on injection of depolarizing current the fibers responded with repetitive action potentials. In normal interstitial fluid the current voltage relationship was N-shaped, with a region of negative slope between -70 and -55 mV. Replacement of chloride by an impermeant anion changed this relationship very little, suggesting an abnormally small chloride conductance. The potassium current through the inward-going rectifier was larger than normal. The force of tetanic contractions of a rested bundle was not sustained but fell quickly to a plateau that increased with repeated stimulation. The relaxation of a rested tetanus was slow and accompanied by spontaneous electrical activity. In subsequent contractions the relaxation became faster and electrical after activity decreased. However at 23 degrees C the speed of relaxation was always high despite a large amount of electrical after-activity. The electrical instability of the membrane and the transient weakness can be explained on the basis of the N-shaped membrane characteristic. PMID- 3352657 TI - Morphometry of intramuscular nerves in amyotrophic lateral sclerosis. AB - Morphometric analysis of 90 intramuscular nerves from the biopsied biceps muscles of 16 cases of amyotrophic lateral sclerosis (ALS) were done and compared with controls. In all fascicles (large and small) of ALS, the total number and the numbers of large and small myelinated fibers were significantly reduced to 52, 16, and 64% of controls, respectively. A histogram of the largest fascicles revealed a unimodal distribution and a shift to the left, showing a single peak at 1 micron diameter. The results indicate proximal and distal involvement of the most remote portions of the nerves to the muscle in ALS and support previous suggestions of a neuronopathy. PMID- 3352656 TI - Detection of muscle injury in humans with 31-P magnetic resonance spectroscopy. AB - Strenuous exercise can result in muscle injury that may persist for 2 weeks. Our purpose was to determine if muscle injury can be detected with 31-P magnetic resonance spectroscopy. Normal subjects performed repeated lengthening contractions with either arms or legs designed to result in mild muscle injury. One hour after the arm exercise, there was a significant increase in the inorganic phosphate to phosphocreatine ratio (Pi/PCr), with the maximum increase in Pi/PCr occurring 1 day postexercise (0.12 +/- 0.01 to 0.21 +/- 0.05). Pi/PCr remained elevated for 3-10 days. Similar results were seen following the leg exercise protocol. ATP/(Pi + PCr) decreased in all the arm exercised subjects. Exercise protocols that did not contain lengthening contractions did not result in changes of Pi/PCr or ATP/(Pi + PCr). Patients with various neuromuscular diseases with evidence of muscle damage (elevated CK, muscle soreness, and histopathological findings) also showed increased Pi/PCr at rest. We conclude that elevated Pi/PCr at rest can reflect nonspecific muscle damage in normal and diseased subjects. PMID- 3352658 TI - Adaptation of skeletal muscle to immobilization in a shortened position. AB - This study determined the morphological changes and adaptations that occur following immobilization of rat soleus and gastrocnemius muscles when the ankle joint is placed in complete plantar flexion for 2, 5, 7, 14, 21, and 28 days by means of plaster casts. Previous studies of such shortened muscles have shown that the number of sarcomeres in series is reduced, but how the sarcomeres are reduced has not been determined. We observed that the fibers in the mid-belly region of the muscles demonstrated a progressive degenerative process over the first few weeks. Myofibrils across the entire width of the affected fibers underwent dissolution. However, by 4 weeks new myofibrils were being formed, and sarcomere lengths appeared normal. Portions of the fibers near the tendon underwent segmental necrosis. These findings are similar to the response of the soleus and gastrocnemius muscles to tenotomy and are clinically relevant to orthopedic procedures that maintain muscles in shortened conditions for prolonged periods. PMID- 3352659 TI - Association between biochemical and physiological properties in single motor units. AB - Motor units from the cat tibialis posterior muscle were examined for an association between physiological and biochemical properties. Functionally isolated motor units were categorized on the basis of their physiological properties. This was followed by quantitative microbiochemical analysis of single muscle fibers from each unit, identified in cross sections using the glycogen depletion method. The activities of malate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase distinguished between fatigable (type FF) and fatigue-resistant (types FR and S) units. The activities of both lactate dehydrogenase and adenylokinase were higher in fast- than in slow-contracting units. Cluster analyses, based on both physiological and biochemical properties or on biochemical properties alone, produced groupings identical to types FF, FR, and S. The association between physiological and biochemical properties substantiates the idea that biochemically distinct groups of motor units correspond to physiologically identifiable groups. PMID- 3352660 TI - Continuous motor unit activity confined to the upper extremities. AB - We report a patient with clinical vermiform motor activity, muscle cramps, delayed relaxation of grip, and continuous motor unit discharges who developed mild symmetric symptoms in the upper extremities following a viral infection. Treatment with carbamazepine produced considerable symptomatic improvement. Needle electromyography (EMG) in several muscles showed irregular grouped spontaneous discharges composed of potentials resembling normal motor units. The discharges occurred asynchronously in distal muscles with identical and different peripheral nerve innervation but were not seen in more proximal muscles innervated by the same nerves. Our EMG findings indicate an origin of this spontaneous activity in the terminal branched motor nerves. PMID- 3352661 TI - Sympathetic skin response in diabetic peripheral neuropathy. AB - There were 72 diabetic patients with clinical evidence of sensorimotor peripheral neuropathy investigated to determine the sensitivity of the sympathetic skin response test (SSR) for detection of sudomotor dysfunction and its correlation with other autonomic function tests, autonomic symptoms, and degree of peripheral neuropathy. Nerve conduction velocities (NCV) were abnormal in all patients, SSR was absent in 60 of 72 patients (83%), Valsalva test was abnormal in 32 of 67 patients (48%) who had the test, and 6 of 72 (9%) had orthostatic hypotension. Statistically significant correlation was found between the Valsalva test abnormality, the degree of peripheral neuropathy, and the SSR in our patients. All patients with orthostatic hypotension had an absent SSR and an abnormal Valsalva test. Most patients had one or more autonomic signs or symptoms. Orthostatic dizziness only correlated with SSR, however. These results suggest that sudomotor activity detected by sympathetic skin response is a valuable test for investigation of dysautonomia in diabetic peripheral neuropathy. PMID- 3352662 TI - Nature of the sensory loss in leprosy. PMID- 3352663 TI - ALS CSF: effect on cultured neurons. PMID- 3352664 TI - Syringomyelia: electrophysiologic aspects. PMID- 3352665 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 13-1988. Pelvic mass in a 42-year-old woman with a history of salmonella sepsis. PMID- 3352666 TI - Coverage of the uninsured and underinsured. A proposal for school enrollment based family health insurance. PMID- 3352667 TI - Medicine and the nature of vertical reasoning. PMID- 3352668 TI - Corticosteroids and allergies to contrast material. PMID- 3352669 TI - Case 34-1987. PMID- 3352670 TI - Hydroxyl radical formation in neutrophils. PMID- 3352671 TI - What is quality care? PMID- 3352672 TI - Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. AB - Autografting of dopamine-producing adrenal medullary tissue to the striatal region of the brain is now being attempted in patients with Parkinson's disease. Since the success of this neurosurgical approach to dopamine-replacement therapy may depend on the selection of the most appropriate subregion of the striatum for implantation, we examined the pattern and degree of dopamine loss in striatum obtained at autopsy from eight patients with idiopathic Parkinson's disease. We found that in the putamen there was a nearly complete depletion of dopamine in all subdivisions, with the greatest reduction in the caudal portions (less than 1 percent of the dopamine remaining). In the caudate nucleus, the only subdivision with severe dopamine reduction was the most dorsal rostral part (4 percent of the dopamine remaining); the other subdivisions still had substantial levels of dopamine (up to approximately 40 percent of control levels). We propose that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits (in "higher" cognitive functions) are, if present, less marked or restricted to discrete functions only. We conclude that the putamen--particularly its caudal portions--may be the most appropriate site for intrastriatal application of dopamine-producing autografts in patients with idiopathic Parkinson's disease. PMID- 3352673 TI - Why there will be little or no physician surplus between now and the year 2000. AB - Most observers think that by the year 2000 there will be a considerable surplus of physicians in the United States. In this paper we present a new framework for estimating the future balance between supply and demand with respect to physicians' services. Our analysis suggests that even if competitive medical plans serve approximately half the population by the year 2000, there will probably be little or no physician surplus. Moreover, if a slight surplus should occur, it is likely to be largely erased by increased involvement of physicians in administrative activities and a variety of nontraditional clinical activities that currently occupy little of a physician's time. Our prediction of little or no surplus could be altered appreciably, however, by two forces that would have opposite effects: an acceleration of technological change would increase demand beyond our projections, whereas widespread rationing of beneficial services would constrain the demand for physicians' services. PMID- 3352674 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 14-1988. A 40-year-old man with rapidly progressive blindness and multiple cranial-nerve deficits. PMID- 3352676 TI - Beyond GMENAC--another physician shortage from 2010 to 2030? PMID- 3352675 TI - Reporting the aspirin study: the Journal and the media. PMID- 3352677 TI - The aspirin-heart study and the Journal's embargo policy. PMID- 3352678 TI - An overview of the British and American aspirin studies. PMID- 3352679 TI - The physicians' health study: aspirin for the primary prevention of myocardial infarction. PMID- 3352680 TI - Disturbing dreams with long-acting verapamil. PMID- 3352682 TI - Protein C deficiency and the risk of venous thrombosis. PMID- 3352681 TI - Continuous axillary plexus block in the treatment of accidental intraarterial injection of cocaine. PMID- 3352683 TI - Video-camera vision: transient monocular diplopia. PMID- 3352684 TI - High-technology medicine in China. The case of chronic renal failure and hemodialysis. PMID- 3352685 TI - Cigarette smoking and risk of stroke in middle-aged women. AB - It is known that cigarette smoking is associated with increased risk of both thrombotic and hemorrhagic stroke among men. To test for such an association among women, we examined the incidence of stroke in relation to cigarette smoking in a prospective cohort study of 118,539 women 30 to 55 years of age and free from coronary heart disease, stroke, and cancer in 1976. During eight years of follow-up (908,447 person-years), we identified 274 strokes, comprising 71 subarachnoid hemorrhages, 26 intracerebral hemorrhages, 122 thromboembolic strokes, and 55 strokes about which information was insufficient to permit classification. The number of cigarettes smoked per day was associated positively with the risk of stroke. Compared with the women who had never smoked, those who smoked 1 to 14 cigarettes per day had an age-adjusted relative risk of 2.2 (95 percent confidence interval, 1.5 to 3.3), whereas those who smoked 25 or more cigarettes per day had a relative risk of 3.7 (95 percent confidence interval, 2.7 to 5.1). For women in this latter group, the relative risk of subarachnoid hemorrhage was 9.8 (95 percent confidence interval, 5.3 to 17.9), as compared with those who had never smoked. Adjustment for the effects of relative weight, hypertension, diabetes, history of high cholesterol, previous use of oral contraceptives, postmenopausal estrogen therapy, and alcohol intake did not appreciably alter the association between cigarette use and incidence of stroke. These prospective data support a strong causal relation between cigarette smoking and stroke among young and middle-aged women. PMID- 3352686 TI - The mortician's mystery. Gynecomastia and reversible hypogonadotropic hypogonadism in an embalmer. PMID- 3352687 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 15-1988. A 26-year-old woman with cardiomyopathy, multiple strokes, and an adrenal mass. PMID- 3352688 TI - Discontinuing antiepileptic drugs. PMID- 3352689 TI - Ethical decisions in discontinuing mechanical ventilation. PMID- 3352690 TI - Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. PMID- 3352691 TI - Dietary potassium and stroke. PMID- 3352692 TI - Male hypogonadism and bone fracture. PMID- 3352694 TI - Gifts from the sea for medicine. PMID- 3352693 TI - Maternal-fetal transmission of myasthenia gravis with acetylcholine-receptor antibody. PMID- 3352696 TI - Carcinoma of the urinary bladder after treatment with cyclophosphamide for non Hodgkin's lymphoma. AB - We observed nine cases of transitional-cell carcinoma of the urinary bladder among patients who had had long-term treatment of other cancers with cyclophosphamide. Seven of the bladder carcinomas occurred within a cohort of 471 patients treated for non-Hodgkin's lymphomas. In this cohort the relative risk of bladder cancer was 6.8 (95 percent confidence interval, 3.2 to 14.2). The cumulative risk (mean +/- SE) was 3.5 +/- 1.8 percent 8 years after the start of treatment with cyclophosphamide and 10.7 +/- 4.9 percent after 12 years. Three of the nine patients were 50 years of age or younger; seven died with progressive bladder cancer. Subsequently, an additional patient had acute nonlymphocytic leukemia. Hemorrhagic cystitis was observed in 33 patients (cumulative risk, 11.8 +/- 2.1 percent after five years). Development of carcinoma of the urinary bladder was not related to previous hemorrhagic cystitis. The results caution against long-term treatment with cyclophosphamide for diseases with a favorable prognosis. PMID- 3352695 TI - Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease. AB - To assess the causal relation between acute mental stress and myocardial ischemia, we evaluated cardiac function in selected patients during a series of mental tasks (arithmetic, the Stroop color--word task, simulated public speaking, and reading) and compared the responses with those induced by exercise. Thirty nine patients with coronary artery disease and 12 controls were studied by radionuclide ventriculography. Of the patients with coronary artery disease, 23 (59 percent) had wall-motion abnormalities during periods of mental stress and 14 (36 percent) had a fall in ejection fraction of more than 5 percentage points. Ischemia induced by mental stress was symptomatically "silent" in 19 of the 23 patients with wall-motion abnormalities (83 percent) and occurred at lower heart rates than exercise-induced ischemia (P less than 0.05). In contrast, we observed comparable elevations in arterial pressure during ischemia induced by mental stress and ischemia induced by exercise. A personally relevant, emotionally arousing speaking task induced more frequent and greater regional wall-motion abnormalities than did less specific cognitive tasks causing mental stress (P less than 0.05). The magnitude of cardiac dysfunction induced by the speaking task was similar to that induced by exercise. Personally relevant mental stress may be an important precipitant of myocardial ischemia--often silent--in patients with coronary artery disease. Further examination of the pathophysiologic mechanisms responsible for myocardial ischemia induced by mental stress could have important implications for the treatment of transient myocardial ischemia. PMID- 3352697 TI - Medically inappropriate hospital use in a pediatric population. AB - To assess the extent of inappropriate hospital use in pediatric inpatients, I modified the Appropriateness Evaluation Protocol (AEP)--developed to assess inappropriate hospital use in adults--to apply to children and used it to evaluate pediatric inpatients retrospectively for every 10th day, from July 1982 to July 1983, at the University of Wisconsin Hospital. Of 1098 patient-days evaluated, 21.4 percent were judged to represent inappropriate hospital use on the basis of the protocol's criteria. The rate of inappropriate use varied according to admitting specialty, ranging from 7 of 70 days (10 percent) for pulmonary medicine to 43 of 61 days (70 percent) for neurology (P less than 0.005). There was a tendency toward lower rates of inappropriate use in uninsured patients (6 of 44 days [14 percent] vs. 226 of 1038 days [22 percent] in patients with Medicaid or private insurance, P = 0.13), and rates were lower in younger children (74 of 432 days [17 percent] in children less than or equal to 5 years of age vs. 162 of 656 days [25 percent] in children greater than 5 years of age, P less than 0.005). There was no variation according to sex, day of the week, or month. Contrary to expectations, inappropriate use decreased with increased lengths of stay (for stays of 1 day, 8 of 13 days were inappropriate [61 percent]; for stays of 2 to 6 days, 118 of 410 days were inappropriate [29 percent]; for 7 to 13 days, 58 of 291 [20 percent]; and for greater than or equal to 14 days, 51 of 362 [14 percent], P less than 0.001). I conclude that there is a substantial rate of inappropriate hospital use in pediatrics and that such use is more likely during short admissions than during long ones. Cost-containment efforts directed at limiting the length of hospitalization may therefore not reduce inappropriate hospital use in this population. PMID- 3352698 TI - Selective reduction of multifetal pregnancies in the first trimester. PMID- 3352699 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-1988. An 83-year-old woman with anemia, oliguric renal failure, and past lymphoma. PMID- 3352700 TI - Myocardial ischemia in coronary disease. PMID- 3352701 TI - Stiff-man syndrome--an autoimmune disease? PMID- 3352702 TI - Selective reduction--a perinatal necessity? PMID- 3352703 TI - Persistence of Streptococcus mitis in an aortic vegetation after 25 days of penicillin-netilmicin combination therapy. PMID- 3352704 TI - Sodium chloride and essential hypertension. PMID- 3352705 TI - Genetic factors in abdominal obesity, a risk factor for stroke. PMID- 3352707 TI - A new waiting game. PMID- 3352706 TI - Plasma glycocalicin. PMID- 3352708 TI - Effect of generous funding for AIDS research on general biomedical research. PMID- 3352709 TI - Neck-cracker neuropathy. PMID- 3352710 TI - Body fat and the activity of the autonomic nervous system. AB - The cause of most cases of human obesity is unknown. Specific alterations in the activity of the autonomic nervous system may mediate and perhaps cause obesity in animal models. We therefore looked for alterations in autonomic activity in human obesity. Fifty-six healthy men with various percentages of body fat underwent autonomic testing while at rest. Significant correlations were found between the percentage of body fat and the variation in the R-R interval after beta adrenergic blockade (r = -0.30, P less than 0.03), the heart rate (r = 0.30, P less than 0.03), the plasma norepinephrine concentration (r = -0.30, P less than 0.05), the plasma epinephrine concentration (r = -0.49, P less than 0.001), and the pupillary latency period (r = 0.39, P less than 0.01). Each of these variables reflects the activity of the sympathetic nervous system or parasympathetic nervous system or both. Depressions in sympathetic and parasympathetic activity were significantly but weakly associated with increasing percentages of body fat. These associations indicate that in obese persons, autonomic changes, though not necessarily causal, involve several organ systems. We suggest that autonomic alterations are important in human obesity, as they are in animal obesity. A disordered homeostatic mechanism may promote excessive storage of energy by decreasing sympathetic activity, while defending against weight gain by decreasing parasympathetic activity. The use of autonomic profiles holds promise for classifying human obesity and identifying obese patients at increased risk for various disorders. PMID- 3352711 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 17-1988. A 40-year-old man with a cerebral mass one month after severe pain in the region of an upper tooth. PMID- 3352712 TI - More on the Ingelfinger rule. PMID- 3352713 TI - Macular hemorrhage in the aging eye: the effects of anticoagulants. PMID- 3352714 TI - Diet pills and sudden death. PMID- 3352715 TI - Respiratory distress in twins. PMID- 3352716 TI - Testicular torsion in a hot country. PMID- 3352718 TI - The reform of health care. PMID- 3352717 TI - More on simplified calculation of body-surface area. PMID- 3352719 TI - The medical clerkship. PMID- 3352720 TI - Production of sterigmatocystin by Aspergillus versicolor isolated from roughage. AB - A total of 69 samples of hay and straw collected during the winter period of 1984/85 were surveyed for their contamination by Aspergillus versicolor. The percentage of A. versicolor-positive samples was 14.5%. Nineteen A. versicolor strains mainly isolated from roughage were tested for the production of sterigmatocystin. All of the isolates examined were capable of producing different levels of sterigmatocystin on a cracked corn substrate. The majority of these strains were highly toxigenic; 53% of the isolates produced more than 500 mg/kg of sterigmatocystin. These findings suggest that corn is a very suitable substrate for sterigmatocystin production and that particularly in the surface layers of feed stocks and corn silos such toxigenic strains of A. versicolor can produce considerable growth and possibly sterigmatocystin, too. PMID- 3352722 TI - Fungal volatiles associated with moldy grain in ventilated and non-ventilated bin stored wheat. AB - The fungal odor compounds 3-methyl-1-butanol, 1-octen-3-ol and 3-octanone were monitored in nine experimental bins in Winnipeg, Manitoba containing a hard red spring wheat during the autumn, winter and summer seasons of 1984-85. Quality changes were associated with seed-borne microflora and moisture content in both ventilated and non-ventilated bins containing wheat of 15.6 and 18.2% initial moisture content. All three odor compounds occurred in considerably greater amounts in bulk wheat in non-ventilated than in ventilated bins, particularly in those with wheat having 18.2% moisture content. The presence of these compounds usually coincided with infection of the seeds by the fungi Alternaria alternata (Fr.) Keissler, Aspergillus repens DeBarry, A. versicolor (Vuill.) Tiraboschi, Penicillium crustosum Thom, P. oxalicum Currie and Thom, P. aurantiogriesum Dierckx, and P. citrinum Thom. High production of all three odor compounds in damp wheat stored in non-ventilated bins was associated with heavy fungal infection of the seeds and reduction in seed germinability. High initial moisture content of the harvested grain accelerated the production of all three fungal volatiles in non-ventilated bins. PMID- 3352723 TI - AIDS and public opinion in France. PMID- 3352725 TI - Cash windfall for UK pioneers of MRI. PMID- 3352724 TI - HIV-2 detected in UK. PMID- 3352726 TI - CNRS outlines its biology plans to 1990. PMID- 3352721 TI - Paracoccidioidomycosis in nude mice: presence of filamentous forms of the fungus. AB - Congenitally athymic nude mice (nu/nu) and their phenotypically normal littermates (nu/+) were intraperitoneally infected with yeast cells of a strain of Paracoccidioides brasiliensis. The nude mice developed a severe and generalized infection with an intense parasitism of several organs, accompanied by a low-grade of tissue reaction. The lesions were characterized by abundant yeast-like cells of the fungus, and in some animals, numerous hyphal forms could be well visualized. In control animals, infection was moderate, almost exclusively restricted to the area of inoculation, and the lesions presented few parasites surrounded by an inflammatory response. Filamentous forms of the fungus were never encountered in these animals. PMID- 3352727 TI - UK's biotechnology lacking specialists. PMID- 3352728 TI - Moral failure? PMID- 3352729 TI - Protein structure. An extra dimension to NMR. PMID- 3352730 TI - Neural populations revealed. PMID- 3352731 TI - AIDS incubation period in haemophiliacs. PMID- 3352732 TI - Solitons and energy transfer in DNA. PMID- 3352733 TI - Population coding of saccadic eye movements by neurons in the superior colliculus. AB - The deeper layers of the superior colliculus are involved in the initiation and execution of saccadic (high velocity) eye movements. A large population of coarsely tuned collicular neurons is active before each saccade. The mechanisms by which the signals that precisely control the direction and amplitude of a saccade are extracted from the activity of the population are unknown. It has been assumed that the exact trajectory of a saccade is determined by the activity of the entire population and that information is not extracted from only the most active cells in the population at a subsequent stage of neural processing. The trajectory of a saccade could be based on vector summation of the movement tendencies provided by each member of the population of active neurons or be determined by a weighted average of the vector contributions of each neuron in the active population. Here we present the results of experiments in which a small subset of the active population was reversibly deactivated with lidocaine. These results are consistent with the predictions of the latter population averaging hypothesis and support the general idea that the direction, amplitude and velocity of saccadic eye movements are based on the responses of the entire population of cells active before a saccadic eye movement. PMID- 3352734 TI - Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo. AB - Cutting the axons of the cholinergic neurons that project to the hippocampal formation results in death of most of these cells. Previous studies have shown that administration of nerve growth factor before or at the same time as the lesion will prevent this cell death. Here we demonstrate that basic fibroblast growth factor (FGF) administered into the brain reduces the death of cholinergic neurons in the medial septum and diagonal band of Broca after transection of their axons, in both young adult and aged rats. Moreover, FGF can partially protect against death of cholinergic neurons even when administered two days after axonal transection. These results indicate a possible function for FGF in the normal support of basal forebrain cholinergic neurons, but its range of activity could be wider, for FGF also supports noncholinergic neurons in vitro, it is localized in many of the central nervous system neurons, and it is found in relatively high concentrations in the brain. PMID- 3352736 TI - Three-dimensional NMR spectroscopy of a protein in solution. AB - The geometric information used to solve three-dimensional (3D) structures of proteins by NMR spectroscopy resides in short (less than 5 A) interproton distance data. To obtain these distances, the 1H-NMR spectrum must first be assigned using correlation and nuclear Overhauser effect (NOE) experiments to demonstrate through-bond (scalar) and through-space connectivities, respectively. Because the NOE is proportional to r-6, distance information can then be derived. The increased resolution afforded by extending NMR experiments into a second dimension enables one to detect and interpret effects that would not be possible in one dimension owing to extensive spectral overlap and much reduced information. A number of small protein structures have previously been solved in this way. Extending this methodology to larger proteins, however, requires yet an additional improvement in resolution as overlap of cross-peaks in the two dimensional (2D) NMR spectra present a major barrier to their unambiguous identification. One way of increasing the resolution is to extend the 2D-NMR experiments into a third dimension. We report here the applicability of three dimensional NMR to macromolecules using the 46-residue protein alpha 1 purothionin as an example. PMID- 3352735 TI - Stimulus-dependent myristoylation of a major substrate for protein kinase C. AB - Bacterial lipopolysaccharide (LPS), the major surface component of gram-negative bacteria, exerts a profound effect on the immune system by enhancing the release of proteins and arachidonic acid metabolites from macrophages (for review see ref. 1). The molecular mechanism(s) by which LPS induces these various secretory responses is unknown. We previously reported that LPS promotes the myristoylation of several macrophage proteins including one with a relative molecular mass (Mr) of 68K2. We have now found that by several criteria the 68K myristoylated protein is similar or identical to the 80/87K protein, a major specific substrate for protein kinase C (PKC) found in brain and fibroblasts (for review see refs 7,8). We have also found that the myristoylated PKC substrate is quantitatively associated with the membrane fraction. Myristoylation of the PKC substrate may target it to the membrane and constitute a transduction pathway for stimulus response coupling. PMID- 3352738 TI - Funding needed for private enterprise in genome sequencing. PMID- 3352737 TI - South Africa uses deportation in the battle against AIDS. PMID- 3352739 TI - Self-assembling surfaces. PMID- 3352740 TI - Evolution of the third kind. PMID- 3352741 TI - Receptive fields in the body-surface map in adult cortex defined by temporally correlated inputs. AB - Receptive fields (RFs) obtained at specific cortical sites can be used to define a topographic map of the body surface in adult mammalian somatosensory cortex. This map is not static, and RFs at particular cortical sites can change in size and location throughout adult life. Conversely, the cortical loci at which a given skin surface is represented can shift hundreds of micrometres across the cortex in the koniocortical field, area 3b (refs 1-12). This plasticity suggests that RFs derive not from rigid anatomical connections, but by the selection of a subset of a large number of inputs. We have proposed that inputs are selected on the basis of temporal correlation 11-15. Here we test this idea by altering the correlation of inputs from two adjacent digits on the adult owl monkey hand by surgically connecting the skin surfaces of the two fingers (the formation of syndactyly). This manipulation increases the correlation of inputs from skin surfaces of adjacent fingers. The striking discontinuity between the zones of representation of adjacent digits on the somatosensory cortex disappeared. These results support the hypothesis that the topography of the body-surface map in the adult cortex is influenced by the temporal correlations of afferent inputs. PMID- 3352742 TI - Immediate and chronic changes in responses of somatosensory cortex in adult flying-fox after digit amputation. AB - The somatosensory cortex of adult mammals has been shown to have a capacity to reorganize when inputs are removed by cutting afferent nerves or amputating a part of the body. The area of cortex that would normally respond to stimulation of the missing input can become responsive to inputs from other parts of the body surface. Although a few animals have been studied with repeat recording, no attempt has been made to follow the time-course of changes at cortical loci and the immediate effects of a small amputation have not been reported. We have followed the changes in response in the primary somatosensory cortex in the flying-fox following amputation of the single exposed digit on the forelimb. Immediately after amputation, neurons in the area of cortex receiving inputs from the missing digit were not silent but responded to stimulation of adjoining regions of the digit, hand, arm and wing. In the week following amputation, the enlarged receptive fields shrank until they covered only the skin around the amputation wound. The immediate response is interpreted as a removal of inhibition and the subsequent shrinking of the field may be due to re establishment of the inhibitory balance in the affected cortex and its inputs. PMID- 3352743 TI - Cholinergic-rich brain transplants reverse alcohol-induced memory deficits. AB - Alcohol-induced memory impairment in man has been attributed to deficiencies in subcortical noradrenergic and cholinergic systems, as well as to damage in midbrain structures. Korsakoff's psychosis, a disease in which alcohol poisoning causes apparently irreversible memory defects, is characterized by lesions in cholinergic and noradrenergic nuclei and by a decrease in the activity of choline acetyltransferase (ChAT) and the content of noradrenaline (NA) in forebrain areas such as cerebral cortex and hippocampus, innervated by these nuclei. Prolonged intake of ethanol in rodents similarly produces signs of noradrenergic and cholinergic deafferentation in the cortex and hippocampus, as well as persistent memory deficits. To test whether alcohol-induced memory impairments depend on cholinergic deafferentation, we transplanted cholinergic-rich fetal basal forebrain cell suspensions into the cortex and hippocampus of alcohol-treated rats. The substantial and persistent memory losses produced in our rats by ethanol intake were associated with an impairment of cholinergic function, and were reversed by cholinergic-rich transplants into cortex and hippocampus. PMID- 3352744 TI - The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase. AB - Neuroleukin (NLK) is a protein of relative molecular mass (Mr) 56,000 (56K) secreted by denervated rat muscle and found in large amounts in muscle, brain, heart and kidneys. The protein is a neurotrophic factor for spinal and sensory neurons and a lymphokine product of lectin-stimulated T-cells. It also induces immunoglobulin secretion by human mononuclear cells. Molecular clones of NLK have been expressed in monkey COS cells and the product was shown to have the same biological and biochemical properties as the extracted protein. NLK is abundant in muscle, brain and kidney, but is active at concentrations of 10(-9) to 10(-11) M, similar to those for other polypeptide factors. We have cloned the gene for pig muscle phosphohexose isomerase (PHI) (EC 5.3.1.9) which catalyses the conversion of glucose-6-phosphate to fructose-6-phosphate, an obligatory step in glycolysis, and determined its amino-acid sequence. Surprisingly, it is 90% homologous to the sequence of mouse neuroleukin. PMID- 3352745 TI - Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences. AB - Neuroleukin is a neurotrophic factor of relative molecular mass (Mr) 56,000 (56K) found in skeletal muscle, brain, heart and kidneys which supports the survival of embryonic spinal neurones, skeletal motor neurones and sensory neurones. Neuroleukin is also a lymphokine product of lectin-stimulated T cells and induces immunoglobulin secretion by cultured human peripheral blood mononuclear cells. Mouse neuroleukin has been cloned, the complete nucleotide sequence has been determined and its complementary DNA has been transiently expressed in monkey COS 1 cells. The serum-free supernatant of the transfected, but not of control mock transfected, cells was shown to mimic the properties of neuroleukin isolated from mouse salivary glands. In our work on the molecular genetics of carbohydrate metabolism we have recently isolated a mouse glucose-6-phosphate isomerase (or phosphoglucose isomerase, PGI) cDNA clone using the yeast PGI gene (PGI 1) as a probe. We report here that there is complete sequence identity between the 759 nucleotides at the 3' end of this clone (coding and non-coding) and the sequence of mouse neuroleukin. PMID- 3352746 TI - Human gene expression first occurs between the four- and eight-cell stages of preimplantation development. AB - The earliest stages of development in most animals, including the few mammalian species that have been investigated, are regulated by maternally inherited information. Dependence on expression of the embryonic genome cannot be detected until the mid two-cell stage in the mouse, the four-cell stage in the pig (J. Osborn & C. Polge, personal communication), and the eight-cell stage in the sheep. Information about the timing of activation of the embryonic genome in the human is of relevance not only to the therapeutic practice of in vitro fertilization and embryo transfer (IVF), but more importantly for the successful development of techniques for the preimplantation diagnosis of certain inherited genetic diseases. We describe here changes in the pattern of polypeptides synthesized during the pre-implantation stages of human development, and demonstrate that some of the major qualitative changes which occur between the four- and eight-cell stages are dependent on transcription. In addition, it appears that cleavage is not sensitive to transcriptional inhibition until after the four-cell stage. PMID- 3352747 TI - The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. AB - Two glucose-regulated proteins, GRP78 and GRP94, are major constituents of the endoplasmic reticulum (ER) of mammalian cells. These proteins are synthesized constitutively in detectable amounts under normal growth conditions; they can also be induced under a variety of conditions of stress including glucose starvation and treatment with drugs that inhibit cellular glycosylation, with calcium ionophores or with amino-acid analogues. Unlike the closely-related heat shock protein (HSP) family, the GRPs are not induced significantly by high temperature. Recently, GRP78 has been identified as the immunoglobulin heavy chain binding protein (BiP) (ref. 5 and Y.K. et al., in preparation) which binds transiently to a variety of nascent, wild-type secretory and transmembrane proteins and permanently to malfolded proteins that accumulate within the ER. We have tested the hypothesis that the presence of malfolded proteins may be the primary signal for induction of GRPs by expressing wild-type and mutant forms of influenza virus haemagglutinin (HA) in simian cells. Only malfolded HAs, whose transport from the ER is blocked, induced the synthesis of GRPs 78 and 94. Additional evidence is presented that malfolding per se, rather than abnormal glycosylation, is the proximal inducer of this family of stress proteins. PMID- 3352748 TI - Structure refined to 2A of a nicked DNA octanucleotide complex with DNase I. AB - The cutting rates of bovine pancreatic deoxyribonuclease I (DNase I) vary along a given DNA sequence, indicating that the enzyme recognizes sequence-dependent structural variations of the DNA double-helix. In an attempt to define the helical parameters determining this sequence-dependence, we have co-crystallized a complex of DNase I with a self-complementary octanucleotide and refined the crystal structure at 2 A resolution. This structure confirms the basic features of an early model, namely that an exposed loop of DNase I binds in the minor groove of B-type DNA and that interactions do occur with the backbone of both strands. Nicked octamer duplexes that have lost a dinucleotide from the 3'-end of one strand are hydrogen-bonded across a two-fold axis in the crystal to form a quasi-continuous double helix of 14 base pairs. The DNA 14-mer has a B-type conformation and shows substantial distortion of both local and overall helix parameters, induced mainly by the tight interaction of Y73 and R38 in the unusually wide minor groove. Directly coupled to the widening of the groove by approximately 3A is a 21.5 degree bend of the DNA away from the bound enzyme towards the major groove, suggesting that both DNA stiffness and groove width are important in determining the sequence-dependence of the enzyme cutting rate. A second cut of the DNA which is induced by diffusion of Mn2+ into the co-crystals suggests that there are two active sites in DNase I separated by more than 15A. PMID- 3352749 TI - Grass-eating leopards: wolves turned into sheep? PMID- 3352750 TI - Conference on the Interaction of Radiation Therapy and Chemotherapy. Williamsburg, Virginia, September 28-October 1, 1986. Proceedings. PMID- 3352751 TI - Increase in hypoxic fraction of human colon tumor xenografts by preirradiation of tumor bed. AB - In these experiments, the normal tissue in the hip region of nude mice was irradiated with 15 Gy of x-rays. One day after irradiation, 1 X 10(7) clone A human adenocarcinoma cells were injected to produce solid xenograft tumors. The stromal damage produced by the x-rays yields inhibition of volumetric growth with the time needed to reach 500 mm3 about 2.2 times that seen in mice bearing tumors in nonirradiated tissue. At a volume of 500-600 mm3, tumors growing in either irradiated or nonirradiated stroma were either sham irradiated or irradiated with a single large dose of 30 Gy of x-rays. These mice were either breathing air or had been asphyxiated with nitrogen gas (10 min) immediately prior to exposure. Tumors were then excised, enzymatically disaggregated into single cells, and assayed in vitro for clonogenic cell survival. The hypoxic fractions were determined according to the parallel line bioassay technique. The hypoxic fraction in control (non-preirradiated mice) was 3.5%. However, the hypoxic fraction in tumors growing in preirradiated sites was 25.1%. Therefore, the growth of solid tumors in damaged normal tissue may be associated with an increased percentage of hypoxic cells, possibly produced by impairment of vascular supply. PMID- 3352752 TI - Development and application of a rat tumor model for human bronchial carcinoma. AB - Five squamous cell carcinomas were induced in the lungs of WAG/Rij rats by radiation emitted from isotopes iridium-192 or iodine-125. Tumor fragments were transplanted subcutaneously in syngeneic hosts for propagation of the tumors. A lung cancer model based on implantation of tumor fragments in the lung has been developed. Tumor implants in the lung grew into large invasive squamous cell carcinomas. Metastases in the renal cortex were frequently observed. Tumor growth was determined from repeated chest radiographs. Volume changes after cytostatic treatment could be monitored accurately up to several months. Squamous cell carcinomas transplanted subcutaneously responded as heterogeneously to a variety of cytostatic drugs as did their human counterparts. Responses of the tumor line L17 to doxorubicin were similar when tumors were growing intrapulmonarily or subcutaneously. However, the response of L33 tumors to cisplatin was different, depending on the location. The tumors growing in the lungs provide a model for realistic testing of regimens involving radiation doses, cytostatic drugs, and combinations thereof. PMID- 3352753 TI - Effect of spirogermanium and radiation therapy on the 9L rat brain tumor model. AB - Spirogermanium (SPG) was investigated in the 9L rat brain tumor model in vivo and in vitro. Used at a single ip dose of 50 or 60 mg/kg or at 5 daily doses of 10 mg/kg, SPG was ineffective in prolonging survival of rats burdened with the intracerebrally implanted tumor, i.e., the median survival time (MST) was the same as that for the controls. Only a schedule of 3 X 20 mg SPG/kg every other day improved the MST compared with controls. Single-dose (20-Gy) radiation therapy (RT, cesium-137 whole-head irradiation) did prolong survival. However, when single-dose SPG was combined with RT (1 hr or 1 day before, or 1 hr after RT), the survival response was worse than after RT alone. When the daily SPG was combined with daily RT (5 doses of 6 Gy), survival was no better than after daily RT alone. In vitro, SPG produces a concentration-dependent, exponential decrease in cell survival as measured by colony formation assay. When combined with radiation, there is an additive effect on cell lethality. Aside from the possibility that SPG does not penetrate the rat brain tumor itself, we have no explanation why SPG shows some activity against human brain tumors and is cytotoxic against 9L cells in vitro, yet is both ineffective by itself and fails to potentiate RT in the 9L rat brain tumor model. PMID- 3352754 TI - Improvement of differential toxicity between tumor and normal tissues using intratumoral injection with or without a slow-drug-release matrix system. AB - The therapeutic effects of cisplatin on tumor and normal tissues were assessed when the drug was given by different administration routes either as free drug or associated with a collagen-based matrix. Tumor response was assessed by growth delay of the murine RIF1 tumor, grown subcutaneously in female C3H/km mice. Normal tissue responses were assessed by plasma clearance of [51Cr]EDTA (giving an estimate of kidney damage), by the drop in peripheral white blood cells, and by a loss in mouse body weight. Intraperitoneal injections of cisplatin were the most toxic to the normal tissues for a given drug dose. Intratumoral injections of matrix-associated drug were the least toxic. Comparison of tumor growth delays for a given normal tissue damage demonstrated the superiority of all intratumoral schedules over the ip route. PMID- 3352755 TI - Response of murine tumors to matrix-associated cisplatin intratumoral implants. AB - The response to collagen matrix-associated cisplatin (cis-DDP-CM) implanted intratumorally into KHT and RIF-1 fibrosarcomas grown sc in C3H mice was studied. The effects on tumor growth as well as body weight and animal survival were assessed. The effect of cis-DDP-CM (8 mg/kg) on the growth of KHT tumor was assessed by determining the number of days required for tumors to grow to three times the pretreatment volume of 100-150 mm3. When cisplatin (cis-DDP) was administered ip, the number of days required for threefold growth was 11.1 +/- 2.5 SE. Administration of cis-DDP-CM intratumorally resulted in a value of 17.2 +/- 1.7 days. Epinephrine (0.1-5.0 mg/kg) was also added to the matrix as a vasoconstrictor to further localize the activity of cis-DDP. This resulted in enhanced antitumor activity and, presumably, lower systemic exposure to cis-DDP. For cis-DDP administered ip, the dose required to kill 50% of the test group at 10 days after injection was approximately 14 mg/kg. When cis-DDP-CM was administered intratumorally in doses less than or equal to 30 mg/kg, no mice died. Loss in mouse body weight (greater than 3 g) was detected with ip doses of cis-DDP at 8 mg/kg, but no weight loss was detected for mice treated with matrix implant delivering cis-DDP doses less than or equal to 25 mg/kg. PMID- 3352756 TI - Effects of matrix-associated chemotherapy in combination with irradiation in vivo. AB - Delay of tumor growth in RIF-1 fibrosarcomas in C3H mice was studied, comparing ip delivery of 5-fluorouracil (5-FU) or cisplatin (cis-DDP) versus collagen matrix-associated intratumoral delivery of drug with and without irradiation to a total dose of 1,500 cGy. For cis-DDP (6 mg/kg), the number of days required for treated tumors to attain three times their original treatment volume was 6.2 +/- 1.6 SE for ip drug and 7.0 +/- 1.3 for intratumoral drug matrix. The use of the vasoactive agent epinephrine (1 mg/kg) in the matrix resulted in a growth delay of 10.1 +/- 2.0 days. Irradiation given 60 minutes after drug administration enhanced the delay of tumor growth to 19.2 +/- 2.6 days for systemic drug and 16.7 +/- 2.5 days for matrix-associated drug. The delay of tumor growth for irradiation plus matrix-associated cis-DDP containing epinephrine was 33.0 +/- 5.4 days. X-rays alone caused a tumor growth delay of 11.2 +/- 1.3 days. Similar results were found for 5-FU at a dose of 50 mg/kg, although the epinephrine in the matrix was not as effective. PMID- 3352757 TI - Administration of radiation or cyclophosphamide versus alternated radiation and cyclophosphamide treatment of primary tumor and pulmonary metastases. AB - The experimental tumor 3924A in ACI rats metastasizes to the lungs, but this is rarely apparent unless the life span of the animal is increased by treatment of the tumor. Pulmonary metastases were prevalent among animals given radiation daily or in multiple fractions per day over periods of 3-4 weeks at total doses ranging from 3,000 to 11,250 rad. Multiple doses of cyclophosphamide, each at the level that was lethal to 10% of the animals, did not cure the primary tumor but appeared to delay the appearance of metastases. Treatment schedules that alternated the delivery of multiple 250-rad fractions of radiation during 2-day periods with cyclophosphamide at a dose of 150 mg/kg for a total of three courses were effective in curing the primary tumor and eliminating pulmonary metastases. PMID- 3352758 TI - Systematic investigation into interaction of ionizing radiation and doxorubicin in the Dunning R3327G prostatic adenocarcinoma model. AB - The interaction of doxorubicin and radiation has been systematically studied in the Dunning R3327G prostatic adenocarcinoma, the preeminent animal model for human prostatic cancer. Subcutaneous tumors (produced by injection of 10(7) cells) were treated when about 1 cm3 in volume (19-22 days postimplant). Each modality was used at 1 of 3 dose levels; 2, 4, and 9 mg/kg for doxorubicin; and 5, 15, and 25 Gy for radiation. Single treatment with each agent was combined, in both sequences and five delay times (0.5, 12, 24, 48, and 120 hr) between agents. Growth of individual tumors was fit to a quadratic exponential growth model which was solved for the growth delay and growth rate at twice initial volume. Analysis of variance identified significant interactions for doxorubicin and radiation (due to drug toxicity), sequence and delay, and sequence and radiation, in addition to the four factors individually. The effect on the tumor of combined doxorubicin and radiation is basically additive. Sequence and delay are important in overall tumor control. PMID- 3352759 TI - Mechanisms of cross-resistance between radiation and antineoplastic drugs. AB - The mechanisms responsible for the cross-resistance between radiation and certain antineoplastic agents have been examined in human ovarian cancer cell lines. Cell lines established from patients at a time when they were resistant to combination chemotherapy regimens, which included cisplatin and an alkylating agent as well as cell lines with resistance induced in vitro to melphalan and cisplatin, all have increased cellular levels of glutathione (GSH) compared with drug-sensitive cell lines from untreated patients. In addition, cell lines with acquired resistance to melphalan and cisplatin, but not to doxorubicin, were cross resistant to radiation. L-Buthionine sulfoximine (BSO), an irreversible inhibitor of gamma-glutamylcysteine synthetase, lowered GSH levels in all the resistant cell lines studied. Lowering of GSH levels to less than 10% of control values potentiated the in vitro cytotoxicity of melphalan and cisplatin. Furthermore, BSO was also shown to potentiate the cytotoxicity of melphalan in a nude mouse model system of ovarian cancer in which mice die of disseminated intra-abdominal carcinomatosis. The BSO administered in the drinking water decreased GSH levels by 96%. A single melphalan treatment of 5 mg/kg following GSH depletion produced a 72% increase in median survival time compared with treatment with melphalan alone. In addition, depletion of GSH levels in cell lines with acquired resistance to melphalan led to a marked sensitization of these cells to irradiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352760 TI - Inhibition of radiation dose-rate-sparing effects in human tumor cells by 3 aminobenzamide. AB - The capacity of two recently established human tumor cell lines (a germ cell carcinoma of the testis and a squamous cell cervical carcinoma) to repair radiation damage has been determined by assessing in vitro cell survival over the dose-rate range of 150-1.6 cGy/minute. Survival after irradiation at a high dose rate (150 cGy/min) showed that the cervical carcinoma was more radioresistant. A dose-sparing effect was observed at low dose rates (3.2 and 1.6 cGy/min), compared to the high dose rate, to a similar extent in both cell lines. In addition, 3-aminobenzamide added 2 hours prior to and removed 18 hours after irradiation caused a small but similar increase in cell kill with the high dose rate in both cell lines. It also steepened the survival curves at low dose rates. Since the survival curves obtained at 1.6 and 3.2 cGy/minute help to define a dominant component of the initial slope of the acute curve, we conclude that 3 aminobenzamide can act as a modifier of this component. PMID- 3352761 TI - Interactions between antitumor drugs and radiation in mammalian tumor cell lines: differential drug responses and mechanisms of resistance following fractionated X irradiation or continuous drug exposure in vitro. AB - Drug-resistant mammalian tumor cell lines have been derived by either fractionated x-irradiation treatment or exposure to vincristine or etoposide (VP 16-213) in vitro. Analyses of the patterns of responses expressed by these differently derived, resistant cell lines have shown variations in responses to a range of antitumor drugs depending upon the agent used to induce resistance. However, all treated cell lines express resistance to vincristine and, with one exception, to VP-16-213. Preliminary evidence has indicated that resistance to vincristine in drug-treated cells, but not x-irradiation-treated cells, is associated with impaired vincristine uptake; resistance to VP-16-213 in both differently derived, resistant sublines is associated with a reduction of VP-16 213-induced DNA single-strand breakage; and collateral sensitivity to cisplatin in x-irradiation-treated cells is associated with enhanced drug-induced DNA cross linking. These data indicate that patterns of responses to antitumor drugs and the mechanisms associated with these altered responses differ depending upon the agent used to induce resistance. PMID- 3352762 TI - Cell-cycle, phase-specific cell killing by carmustine in sensitive and resistant cells. AB - Cell-cycle, phase-specific cell kill caused by carmustine (BCNU) was measured in 4 cell lines with different sensitivities to the drug. Cells were treated with BCNU for 1 hour after which enriched subpopulations in various phases of the cell cycle were obtained by centrifugal elutriation and were assayed for cell survival. Levels of activity of guanine O6-alkyltransferase were measured for each line; intracellular levels of this repair protein have been correlated with cellular resistance to chloroethylnitrosoureas. Only BTRC-19, a clone of the 9L line, had significant levels of alkyltransferase activity and exhibited a relatively flat age-response curve to BCNU. Alkyltransferase activity was not detected in the other 3 cell lines, all of which displayed a similar age response in which G1- and G2/M-phase cells were relatively sensitive to BCNU compared with the response of S-phase cells. We conclude that alkyltransferase activity may overwhelm other determinants that cause cell-cycle phase specificity to BCNU. PMID- 3352763 TI - Chinese hamster pleiotropic multidrug-resistant cells are not radioresistant. AB - The inherent cellular radiosensitivity of a Chinese hamster ovary pleiotropic cell line that is multidrug resistant (CHRC5) was compared to that of its parental cell line (AuxB1). Radiation survival curve parameters n and D0 were 4.5 and 1.1 Gy, respectively, for the CHRC5 line and 5.0 and 1.2 Gy, respectively, for the parental line. Thus, the inherent radiosensitivity of the two lines was similar even though key intracellular free radical scavenging and detoxifying systems employing glutathione, glutathione transferase, and catalase produced enzyme levels that were 2.0-, 1.9-, and 1.9-fold higher, respectively, in the drug-resistant cell line. Glutathione depletion by buthionine sulfoximine resulted in the same extent of aerobic radiosensitization in both lines (approximately 10%). Incorporation of iododeoxyuridine into cellular DNA sensitized both cell lines to radiation. These studies indicate that pleiotropic drug resistance does not necessarily confer radiation resistance. PMID- 3352764 TI - Interaction of cisplatin and x-rays in rat kidney. AB - Cisplatin was administered as a single iv dose of 5 mg/kg in WAG/Rij female rats at intervals of 7 days or 30 minutes before or 7 days after graded irradiation of the left kidney. The unirradiated right kidney was removed 4 weeks after the x ray treatment. Kidney function was determined by measuring urine osmolality and plasma urea. The kidney function parameters did not change measurably in animals treated with cisplatin alone. Only differences in urine osmolality were observed between the groups that received combined treatment or irradiation only. Long term renal fibrosis was assessed by measuring the hydroxyproline content. Significant increases in renal hydroxyproline content were observed in animals receiving treatment with cisplatin either 7 days before or 7 days after irradiation, compared with animals receiving irradiation alone. PMID- 3352766 TI - Radioresistance of human tumor xenografts: possible mechanisms. AB - Cells of three human tumors irradiated in situ in athymic nude mice are more radioresistant at all doses than are corresponding cells irradiated in vitro. The tumors investigated were Na11 melanoma and two colorectal adenocarcinomas, HRT18 and HT29. While the Na11 tumor contains an exceptionally large hypoxic fraction, this is not true for the other two tumors, and other mechanisms have been proposed to explain these findings. Results of experiments described here suggest that the effect is not dependent on intercellular contact or on the age distribution of the cells in vivo. Tumor cells irradiated in situ were sensitized by both high-pressure oxygen and misonidazole, and the effect of the two agents together was greater than that of either used alone. It is concluded from the shape of the survival curve and from the response to high-pressure oxygen and/or misonidazole that the tumor cell population contains cells ranging from acutely hypoxic to fully oxygenated and includes a subpopulation of partially hypoxic cells of intermediate radiosensitivity. PMID- 3352765 TI - Altered radiosensitivity of hematopoietic stem cells by vincristine pretreatment: superoxide dismutase activity as a possible mechanism. AB - The effect of vincristine (VCR) on hematopoietic stem cell and progenitor compartments and its ability to induce transient periods of radioresistance was investigated so that we could ascertain the drug-radiation intertreatment interval affording optimal radioprotection and determine if its ability to induce increased levels of superoxide dismutase (SOD) is a potential mechanism for this radioprotection. Measurement of marrow stem cell and progenitor compartments demonstrated that these subsets displayed differential sensitivity to VCR and that this sensitivity appeared to be proportional to how "primitive" the subset was. Treatment with VCR prior to irradiation was observed to enhance significantly both 8- and 12-day spleen colony-forming unit recovery with maximal radioprotection occurring for a drug-radiation interval of 12-48 hours. Monitoring of copper-zinc SOD levels demonstrated an increase in activity following VCR that was localized in a fraction of the bone marrow enriched for stem cells and progenitors. The temporal pattern of this increase, however, did not correlate with the drug-radiation schedules affording optimal radioprotection, which indicates that other factors appear to be operative in this radioprotection as well. PMID- 3352767 TI - Glutathione as a determinant of cellular response to doxorubicin. AB - We have studied in detail the relationship between glutathione (GSH) depletion and sensitivity of HEp3 human carcinoma cells to doxorubicin [Adriamycin (ADR)]. Exponentially growing HEp3 cells were incubated with L-buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, for different periods so that a range of GSH depletion could be obtained. These GSH-depleted cells were then treated with a combination of BSO and ADR (1 microgram/ml) for various durations. Under these conditions, the cytotoxicity of ADR was significantly enhanced by GSH depletion. The extent of ADR dose enhancement was found to be inversely proportional to cellular GSH level at the time of ADR treatment. Furthermore, it was shown that the dose-enhancement factors (DEF) also correlated with the duration of combined BSO and ADR treatment. For example, at a GSH level of 45% of untreated control, 18.5 +/- 3 fmol/cell or 4.8 +/- 0.3 X 10(-3) fmol/mum3 (+/- SD), DEF of 8.0, 6.4, and 5.0 were obtained for treatment periods of 3 hours, 2 hours, and 1 hour, respectively. Further study showed that the GSH kinetics differed significantly for the different treatment times, which indicates that GSH kinetics may be an important factor in determining the intrinsic sensitivity of HEp3 cells to ADR. Furthermore, the kinetics of GSH response to ADR varied significantly between cell lines. In the study of the effect of such differences, the GSH kinetics of 3 human ovarian tumor cell lines with different intrinsic sensitivities to ADR were investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352768 TI - Cell-cycle dependence of X-ray oxygen effect: role of endogenous glutathione. AB - The oxygen effect was measured in human T-1 cell populations synchronized by mitotic selection and x-irradiated in vitro after they were allowed to progress to six different ages during the division cycle. Survival curves and dose-ratio calculations with 95% confidence intervals were obtained from computer fits of the data to the linear-quadratic model. The oxygen enhancement ratio (OER) values at the 1% survival increased level were 2.6 +/- 0.08 in G1/early S phase and increased to 3.0 +/- 0.15 in late S/G2 phase. The OER values at 10% survival increased linearly from 2.6 +/- 0.2 for G1-phase cells to 3.2 +/- 0.2 for late S/G2-phase cells. The increased OER in S-phase cells was the result of a greater hypoxic radioresistance compared with that measured with G1-phase cells. In parallel experiments with synchronized cell populations, glutathione (GSH) and glutathione disulfide levels were measured by the Tietze assay and also were found to increase over the same period. The molecular mechanisms responsible for the radiation response involve a number of factors, one of which in this cell line may be GSH levels, especially under conditions of hypoxic exposure. Our data are consistent with the hypothesis that G1- to late S-phase, age-dependent fluctuations in GSH content may be correlated with changes in OER during the human T-1 cell cycle. Changes in GSH content relative to its constitutive levels in the cell and alternative reductive factors (i.e., protein thiols), as well as their cellular location, may be important factors in the comparison of these findings to other cell lines. PMID- 3352769 TI - Inhibition of radiation-induced DNA-protein cross-link repair by glutathione depletion with L-buthionine sulfoximine. AB - Cells depleted of their glutathione (GSH) by treatment with L-buthionine sulfoximine (BSO) are more sensitive to ionizing radiation and chemotherapeutic agents. To assess the effects of GSH depletion on repair of radiation-induced DNA damage, we have determined DNA-protein cross-links (DPC) in A549 cells by a nitrocellulose filter binding assay. Untreated A549 cells have a low level of DPC (0.7%), whereas cells incubated with BSO for 92 hours have an elevated level of DPC (1.5%). The dose response for production of radiation-induced DPC is approximately 0.4% DNA bound per 10 Gy for both BSO-treated and non-pretreated cells. Cells not exposed to BSO repair 85% of the radiation-induced DPC in 4 hours. Less repair (55%) is observed for BSO-treated cells incubated for 4 hours postirradiation in conditioned medium, and DPC repair is nearly completely blocked if GSH-depleted cells are given fresh medium during the 4-hour repair interval. The DPC repair is not influenced by the pH of the media between 6.6 and 7.4. Data indicate that intracellular GSH regulates the level of a sulfhydryl containing repair enzyme, and that other, as yet undefined, nutrients may further influence the steady-state level of DPC. PMID- 3352770 TI - Renal damage in mice after treatment with cisplatin and x-rays: comparison of fractionated and single-dose studies. AB - Functional kidney damage in mice was measured after bilateral irradiation with x rays alone or in combination with cisplatin (c-DDP). A single drug dose (6 mg/kg) was injected 30 minutes before the first of four or eight x-ray doses, given as four fractions per day with a minimum interval of 5 hours between treatments. A 30-fraction schedule was also investigated, with 15 fractions given in the first week (3 fractions per day), followed by a 2-week rest period and another 15 fractions in the fourth week. The c-DDP (4 mg/kg) was administered 30 minutes before the first fraction of each week, giving a total drug dose of 8 mg/kg. Renal function was assessed monthly from 10 to 37 weeks after the start of treatment by the clearance of 51Cr-labeled EDTA. The combined treatment caused more kidney damage than either agent alone for all fractionation schedules. Enhancement of the radiation damage by c-DDP changed only slightly with fractionation; dose enhancement factors were 1.2 for 1 fraction to 1.3 for 30 fractions. Modeling studies showed that this was consistent with the additive toxic effects of the two agents. There was no change in the alpha/beta for renal damage after x-rays plus c-DDP, compared with x-rays alone (alpha/beta = 1.9 Gy), implying that there was no reduction in repair and no modification of the x-ray response by c-DDP. PMID- 3352771 TI - Radioprotection of rat subependymal plate with 4-OH sodium butyrate. AB - The central nervous system is a radiation-dose-limiting structure, and cellularity of the rat subependymal plate (a location of neuroglial stem cells) has been used as a model of radiation damage. In the present work, an attempt has been made to improve its radiation tolerance using 4-OH sodium butyrate (gamma OH). Adult rats received 10-Gy 250-kV (peak) x-rays or 3.5-Gy 15-MeV deuterons plus Be neutrons. Cell counts were obtained by histological examination of the subependymal plate. Photon and neutron irradiation alone resulted in a mean cell depletion of 62% and 58%, respectively, compared with sham-irradiated controls, which was not statistically significant; the relative biologic effectiveness was 2.9. In the absence of radiation, gamma OH did not significantly alter the cellularity of the subependymal plate, compared with that in controls treated with chloral hydrate. At doses greater than or equal to 1 g/kg, gamma OH was associated with a statistically significant reduction of subependymal plate cell depletion in animals treated with photon or neutron radiation, and the magnitude of the effect was similar. Arterial blood gas analysis failed to show a significant difference in arterial oxygen tension between control and test animals. PMID- 3352772 TI - Pilot study of interaction of radiation therapy with doxorubicin by continuous infusion. AB - Doxorubicin was initially administered alone by continuous infusion for 5 days every 3 weeks in escalating doses to 13 patients with advanced metastatic and/or recurrent malignancies. The maximum tolerable dosage was 13 mg/m2 per day for 5 days. Kinetic data showed a steady level of 60 ng/ml for 4 days and a biphasic disappearance curve. Radiation therapy (150-200 cGy per session) was then administered in 5-day cycles, every 3 weeks, concomitantly with continuous infusion of doxorubicin (12 mg/m2 per day) to 21 patients with various advanced unresectable recurrent or metastatic malignancies. Four of 9 patients with soft tissue sarcomas achieved complete response after a radiation dose of 2,206 +/- 590 (SD) cGy and 3 had partial response; the median durations of the response were 142 +/- 65 (SD) weeks for complete response and 28 +/- 10 weeks for partial response. Of 4 patients with primary hepatoma, 2 achieved partial response after 1,290 +/- 210 cGy. No response was seen in any of the 7 patients with adenocarcinoma of the gastrointestinal tract or breast. Complications of this regimen included moderate leukopenia and thrombocytopenia, mucositis, skin erythema, and decrease of the ventricular ejection fraction at a cumulative doxorubicin dose of 840 mg/m2. We conclude that doxorubicin given by protracted infusion can be safely administered with concomitant radiation and appears to enhance the effects of radiation on most soft tissue sarcomas and on some hepatocellular carcinomas. PMID- 3352773 TI - Treatment of high-risk sarcomas in children and young adults: analysis of local control using intensive combined modality therapy. AB - Although combination chemotherapy and local irradiation are quite effective treatment for some children and young adults with small round cell sarcomas, high risk patient groups, including patients with localized disease of the trunk and proximal extremity and those who present with metastases, continue to fare poorly with standard combined modality therapy. In an attempt to improve the local and systemic response of these tumors, an intensive treatment protocol was designed that integrates five cycles of chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VADRIAC) plus radiation therapy to the primary tumor (55-60 Gy), bone, and soft tissue metastases (45-50 Gy). Patients achieving complete response to this induction therapy receive intensification treatment with total body irradiation (8.0 Gy), a cycle of VADRIAC, and autologous bone marrow transplantation. All treatment is completed within 6-7 months. From January 1983 to February 1986, 76 consecutive, previously untreated patients were entered in this study; 75 patients are evaluable. Twenty-five patients were diagnosed with rhabdomyosarcoma, 23 with Ewing's sarcoma, 15 with primitive neuroepithelioma, 12 with primitive sarcoma, and 1 patient with metastatic neuroblastoma. Forty-three patients (57%) had metastases at presentation. Overall, 68 of 75 patients (91%) achieved complete response. Fifty-eight of 61 patients with measurable soft tissue masses at the primary site had greater than or equal to 50% tumor reduction with two cycles of chemotherapy prior to local irradiation. Seven patients failed to have complete response at the primary site following five cycles of chemotherapy and local external beam irradiation, although 3 were subsequently rendered locally disease free by intraoperative radiotherapy (2 patients) or surgery (1 patient).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352774 TI - Integration of full-dose adjuvant chemotherapy with definitive radiotherapy for primary breast cancer: four-year update. AB - Controversy exists over the effect of definitive radiotherapy on the ability to administer full doses of adjuvant chemotherapy in primary breast cancer. Ninety six consecutive women with clinical stage I and II breast cancer were treated with radiotherapy plus chemotherapy. Three combinations of drugs were used: cyclophosphamide and 5-fluorouracil (CF); cyclophosphamide, methotrexate, and 5 fluorouracil (CMF); or cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP). Chemotherapy consisted of two cycles of CF (cyclophosphamide at a dosage of 100 mg/m2 orally on days 1-14+5-fluorouracil at 600 mg/m2 iv on days 1 and 8) during concurrent radiotherapy, followed by six cycles of CMFP (same CF dosages+methotrexate at 40 mg/m2 iv on days 1 and 8+prednisone at 40 mg/m2 orally on days 1-14). The study included 63 premenopausal and 33 postmenopausal patients; 72 had 1-3 positive nodes, had greater than or equal to 4 positive nodes, and 9 had negative nodes and negative estrogen receptors. The mean CF doses delivered during concurrent radiotherapy were 95% of the optimal doses, and the mean CMF doses administered during the six cycles after radiotherapy were 89%. The CMF was delivered at level I (greater than or equal to 85% of optimal doses) to 73% of the patients. With a median follow-up of 36 months, 16 relapses have been observed. Two of these patients had treatment failure only in the breast or axilla and are disease free after mastectomy. Of the 72 patients with 1-3 positive nodes, 10 relapsed in distant sites, while 4 of 15 patients with greater than or equal to 4 positive nodes have had distant failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352775 TI - Comparison of total nodal irradiation versus combined sequence of mantle irradiation with mechlorethamine, vincristine, procarbazine, and prednisone in clinical stages I and II Hodgkin's disease: experience of the European Organization for Research and Treatment of Cancer. AB - The H5 study of supradiaphragmatic Hodgkin's disease in clinical stages I-II consisted of two controlled trials adapted to patients considered to have either favorable or unfavorable characteristics, based on prognostic factors identified in two former studies by the European Organization for Research and Treatment of Cancer. Of 494 patients, 257 who were classified as having unfavorable prognosis qualified for the more intensive treatment and consequently were spared a staging laparotomy. They were randomized either to total nodal irradiation (TNI) (132 patients) or to treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternated with mantle irradiation (MOPP X 3-mantle irradiation MOPP X 3; 3M) (125 patients). In complete responders (96%), the 6-year relapse free survival was 77% in the TNI arm and 91% in the 3M arm (P = .02). Relapses in the initially involved and irradiated mantle area were less frequent in patients started on MOPP. The 6-year actuarial total survival (TS) (TNI, 82%, and 3M, 89%; P = .05) appeared to favor the 3M arm, but this difference disappeared when patients dying from causes unrelated to cancer were excluded from analysis. In men less than or equal to 40 years old, there was no difference in relapse-free survival, freedom from disease progression, or TS between the groups receiving TNI and 3M. Thus, TNI is a short and appealing treatment, especially because it preserves fertility. The same observation was true in women less than or equal to 40 years old. In addition, even irradiation less than TNI, which is meant to spare the ovaries, provided a TS similar to that for 3M. PMID- 3352776 TI - Platinum-radiation interactions. AB - The important chemotherapeutic agent cisplatin is currently being combined with radiation therapy (RT) in clinical protocols intended to exploit the potential for this drug to potentiate radiation-induced tumor cell kill. This paper reviews the reports from preclinical studies leading to the design of combined modality protocols and describes the effects produced when platinum complexes are combined with RT. Two interactions that are receiving considerable attention since they might produce an improved therapeutic ratio are the radiosensitization of hypoxic cells and post-RT potentiation of cell kill. This latter effect might include the inhibition of recovery from RT-induced potentially lethal or sublethal damage. However, platinum-radiation interactions are complex and probably include several mechanisms that are unknown at this time. The potential for platinum complexes will be especially promising if results of ongoing phase III combined modality trials show them to be efficacious, since it is unlikely that current protocol designs are optimal. Furthermore, second-generation platinum analogs or other metal complexes designed as potentiators of RT may prove to be more interactive with RT. PMID- 3352777 TI - Combined modality treatment of peritoneal mesotheliomas. AB - Five patients with peritoneal mesothelioma were treated with a multimodality approach consisting of debulking surgery, ip chemotherapy, and whole-abdomen irradiation. Chemotherapy included cisplatin and doxorubicin; radiation was given by an open-field technique. Three patients remain disease free at 46, 60, and 61 months after diagnosis. This treatment approach may serve as a model for common tumors characterized by abdominal carcinomatosis. PMID- 3352779 TI - Concomitant therapy with infusion of cisplatin and 5-fluorouracil plus radiation in head and neck cancer. AB - We have combined cisplatin, 5-fluorouracil infusion, and radiation in an every other-week schedule in a phase I-II study of 44 patients with head and neck cancer to assess toxicity and response. Ten patients were treated palliatively with 2 to 6 cycles of therapy, and 34 were treated curatively with a planned 7 cycles. Of 34 patients treated curatively, all were initially controlled. Three died during treatment (1 myocardial infarction, 1 bowel perforation, and 1 renal failure after amino-glycoside antibiotics). Four patients have had regional recurrences, 7 failed at distant sites (follow-up 2 to 5 yr). Thirty-three percent of 20 patients with complete clinical disappearance of all evidence of their cancer have had a recurrence, as have 38% of 14 (P greater than .1) with some residual abnormalities (partial responders) following treatment. All failures were in the 25 patients with T4 and/or N3 disease. None of the 9 patients with lesser stage IV or stage III disease who were followed for 24 months or more had recurrences. Eighteen patients (53%) survive with a projected 3-year survival of 63% (95% confidence interval 47% to 77%). Nine (27%) have died of disease, 1 (3%) died of a second primary in the head and neck, 3 (9%) of intercurrent disease at 15 to 45 months, and 3 (9%) during treatment. Of the 10 patients treated palliatively, 1 died during treatment with hepatic failure, 6 had complete responses, and 2 had partial responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352778 TI - Simultaneous therapy with high-dose cisplatin and radiation for unresectable squamous cell cancer of the head and neck: a phase I-II study. AB - Studies using simultaneous radiation therapy and conventional doses of cisplatin have suggested improvement in local control and patient survival. This study was undertaken to determine toxicity and patient tolerance to concomitant high-dose cisplatin (40 mg/m2 per day X 5) and radiation (60 Gy in 6 wk +/- 10-Gy boost to residual tumor). Seventeen patients with advanced, inoperable squamous cell cancer primary tumor in the head and neck were treated (15 males and 2 females; median age, 57 yr). Cisplatin was started on day 1 of radiation therapy and repeated every 28 days for three cycles. Normal saline infusion (250 ml/hr) was started 12 hours prior to the first dose and continued 12 hours after the fifth dose. The daily dose of cisplatin was dissolved in 250 ml of 3% NaCl and given over 30 minutes. The cisplatin dose for subsequent cycles was reduced 10 mg/m2 per day only for a nadir granulocyte count less than 500/mm3 or fever greater than 101 degrees F during leukopenia. Of the 17 patients who started therapy, 15 have completed therapy; 1 patient died after one cycle, and 1 died after two cycles. Eleven patients received three cycles of cisplatin, and 10 patients required one dose reduction (6 at course 2 and 4 at course 3). Seven possible infections were successfully treated. Grade 2 neuropathy occurred in 3 patients, and renal toxicity greater than grade 1 occurred in 1 patient. Additional toxic effects were median WBC count nadir of 1.8 X 10(3)/mm3, platelet count nadir of 128 X 10(3)/mm3, hemoglobin nadir of 9.8 g/dl, and median weight loss of 5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352780 TI - Simultaneous radiotherapy and chemotherapy with 5-fluorouracil and cisplatin for locally confined squamous cell head and neck cancer. AB - Fifty-four patients with previously untreated or minimally treated locally confined (MO) squamous cell carcinoma of the head and neck were treated with chemoradiotherapy employing multiple courses of simultaneous radiation, cisplatin, and a 4-day 5-fluorouracil infusion. Twenty-eight patients subsequently underwent definitive surgery, and 26 were treated without surgical resection. Of the 54 patients, 51 were ultimately rendered disease free by this combined modality protocol. The projected relapse-free survival rate for the entire cohort is 71%, with a median relapse-free survival time greater than 17 months. Thirteen patients who had tumors that were technically operable did not undergo surgery after achieving a complete response to induction chemoradiotherapy. Only 1 of these patients experienced subsequent local failure. Although the treatment-associated mucositis and local failure. Although the treatment-associated mucositis and myelosuppression were significant, this chemoradiotherapeutic protocol offers a significant chance of relapse-free survival for all patients with locally confined disease and merits comparison with more standard treatment approaches. PMID- 3352781 TI - Effect of sequencing on combined toxicity of renal irradiation and cisplatin. AB - We are using a rat model to study the effects of sequencing on the combined toxicity of renal irradiation and cisplatin (cis-Pt). Unanesthetized female WAG/RijMCW rats were given bilateral kidney irradiation (20 Gy in 9 fractions), preceded or followed by single ip doses of cis-Pt. Renal irradiation causes an increase in the acute toxicity of cis-Pt given 3-9 months after irradiation. Low dose cis-Pt given immediately before irradiation, or as long as 9 months after irradiation, causes a decrease in the latent period for radiation nephritis and an increase in its severity. When given 3.7 to 7.7 months prior to irradiation, cis-Pt has a less severe effect on radiation nephritis. The greatest enhancement of radiation nephritis is seen for cis-Pt given 3 months after irradiation. Additive effects of cis-Pt and radiation on renal function can explain much, but not all, of the combined toxicity. PMID- 3352782 TI - Sequential administration of methotrexate, cisplatin, and 5-fluorouracil in multimodal therapy for locally advanced head and neck cancer. AB - Thirty-eight previously untreated patients with locally advanced head and neck cancer received three cycles of induction chemotherapy with methotrexate (120 mg/m2) followed by cisplatin (100 mg/m2) and a 5-day continuous infusion of 5 fluorouracil (1,000 mg/m2 per day). The response rate in 34 evaluable patients was 94%, with a complete response rate of 26%. Thirty-one patients underwent local therapy following induction chemotherapy, and 25 (81%) were rendered free of disease: 14 of 15 treated with surgery and radiotherapy and 11 of 16 treated with radiotherapy alone. At a median follow-up of 11 months, 8 patients have relapsed while the remaining 17 patients continue free of disease. The dose limiting toxicity of chemotherapy was mucositis resulting in reduction of the 5 fluorouracil dose in 28 patients. This regimen is highly effective in inducing responses in patients with locally advanced head and neck cancer; 81% of the patients who complete local therapy are rendered free of disease with this multimodal approach. Due to short follow-up, the relapse rate, overall survival, and disease-free survival cannot yet be determined. PMID- 3352783 TI - Chemotherapy with low doses of radiation followed by definitive radiotherapy for advanced unresectable carcinoma of the head and neck. AB - Thirty-six patients with advanced unresectable carcinoma of the head and neck were treated with a combination of three courses of chemotherapy and low doses of radiation, followed after 3 weeks by definitive irradiation. Each course was repeated every 3 weeks with the following sequence. Cisplatin (20 mg/m2) was given in a 20-minute infusion, followed by a 2-hour infusion of 5-fluorouracil (400mg/m2), on days 1,2,5, and 6. Low doses of radiation were given on days 3 and 4, followed by a 2-hour infusion of 5-fluorouracil (400 mg/m2) with a dose of 3 Gy on the target volume. For definitive irradiation, a total dose of 60 Gy was delivered in 30 fractions within 6 weeks. The complete response rate reached 30%, and the partial response rate was 30%. With a median follow-up of 11 months, median overall survival was 10 months; median survival was 21 months for patients with complete response, 9 months for patients with partial response, and 6 months for those with no response (P=.02). PMID- 3352784 TI - New strategies for avoiding total laryngectomy in patients with head and neck cancer. AB - Cisplatin-based chemotherapy has yielded high response rates in patients with head and neck cancer but has failed to improve the survival rates in randomized studies. Thus, its place in the management of head and neck cancer remains unclear. We have been investigating whether the combination of chemotherapy and radical irradiation as an alternative to morbid surgery in selected patients might yield an improved quality of life without compromising survival. Between January 1983 and December 1985, we treated 32 patients with epidermoid carcinoma arising from the larynx, base of the tongue, or hypopharynx, using an interdisciplinary regimen, with the objective of avoiding total laryngectomy. All of these patients had large primary tumors that could not have been removed without total laryngectomy. Patients who could be treated by conservation laryngeal surgery were excluded, as were patients who presented with clearly unresectable disease. The regimen employed cisplatin-based chemotherapy together with brachytherapy and external radiation therapy, with highly individualized treatment planning. Seven patients had T2 lesions, 19 had T3, and 6 had T4. The follow-up periods ranged from 8 to 38 months (median, 18). The actuarial survival rate at 2 years is 85%, and the laryngectomy-free rate at 2 years is also 85%. None of the 11 patients with laryngeal cancer has relapsed, and none has required laryngectomy. None of the 12 patients with base of the tongue cancer treated by brachytherapy has relapsed above the clavicles and none has required laryngectomy, but 1 patient has died of complications of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352785 TI - Clinical experience with high-dose cisplatin and radiation for treatment of epithelial malignancies. AB - Over the past 5 years, 129 patients have been treated with a combination of high dose cisplatin (CDDP) and radiation for locally advanced epithelial malignancies. The CDDP was administered at a dose of 100 mg/m2 by iv infusion over one-half hour, no more than 1 hour before irradiation, every 3 weeks during a full course of external beam irradiation. An attempt was made to take advantage of the interaction of high-dose CDDP and radiation. Tumor systems studied included head and neck, ovary, lung, cervix, and prostate. Median survival times are as follows: squamous cell carcinoma of the head and neck (trial 1), 36 months; ovarian carcinoma, 19; and squamous cell carcinoma of the lung, 14. Median survival has not yet been reached in trials of squamous cell carcinoma of the head and neck (trial 2), cervical carcinoma, or adenocarcinoma of the prostate. PMID- 3352786 TI - Tolerance and preliminary results of simultaneous therapy with radiation and cisplatin for advanced cervical cancer. AB - From 1982 through 1985, 49 women with advanced cervical cancer were treated with concurrent radiation and cisplatin to assess tolerance to the combined modality regimen and its efficacy in comparison to historical controls at the same institution. Eligibility criteria included clinical stage IV disease; para-aortic lymph node metastases; and bilateral, unresectable, and/or multiple (greater than 3) pelvic node metastases. Nodal status was assessed by extraperitoneal surgical staging in the majority of patients with clinical stage I-IVA disease. There was no increase in acute or chronic toxicity compared to historical controls. No patient required reduction of the planned dose of radiation because of acute toxicity. Comparison with historical controls suggests a modest improvement in relapse-free survival in the cisplatin-treated group with positive para-aortic nodes (59% vs. 54% at 2 yr and 59% vs. 42% at 3 yr). We conclude that adjuvant cisplatin can be given simultaneously with radiation for advanced cervical cancer without excessive toxicity or compromise of the radiation regimen. However, confirmation of the modest improvement in relapse-free survival rates for patients with positive para-aortic nodes and identification of other subsets of patients who may benefit will require a prospective randomized trial. PMID- 3352787 TI - Clinical potential of synchronous radiotherapy and chemotherapy for advanced squamous cell carcinoma. AB - The equivocal results of past treatment regimens in which concurrent radiotherapy and chemotherapy were used may have resulted from a lack of site-specific active drugs that were also true radiation sensitizers. This report demonstrates an experience with 3 chemotherapeutic agents, 5-fluorouracil, cisplatin, and mitomycin, given simultaneously with radiation for locally advanced squamous cell carcinomas of such diverse sites as the anal canal, cervix, and esophagus. Early results show that the toxicity of these combination regimens is generally acceptable and indicate that such synchronous combination treatments may be superior in local control and survival to radiotherapy alone. PMID- 3352788 TI - Long-term consequences of chemotherapeutic agents on hematopoiesis: development of altered radiation tolerance. AB - The long-term effects of chemotherapeutic agents on subsequent radiation tolerance of the hematopoietic marrow were studied after a single injection of doxorubicin, 5-fluorouracil, or cyclophosphamide at a maximum tolerated dose. At designated intervals following drug treatment, drug-treated and age-matched control male B6D2F1 mice were exposed to 4.5 Gy of total-body irradiation, and the recovery kinetics of the stem cell (assayed at days 8 and 13 colony-forming spleen units) and progenitor (burst-forming erythroid units, and colony-forming erythroid and granulocyte/macrophage units) compartments were established. Response deficits were calculated for each compartment by comparison of treated and control recovery curves at 5 intervals over 32 weeks. Based on these response deficits, a number of conclusions were drawn: 1) There is selective drug specificity for the more primitive (13d) and mature (8d) CFUs subpopulations; 2) these sensitivities determine the temporal consequences of drug treatment on subsequent radiation tolerance in the marrow (e.g., acute, delayed, or long term); and 3) drugs that influence long-term radiation tolerance of the marrow are dose dependent and initially affect the more primitive stem cells. The data suggest that the initial lesion in the stem cell compartment, resulting in long term enhancement of radiosensitivity, involves a major restriction (either in cell number or in genetic functionality) of the proliferative potential necessary for recovery from subsequent radiation insult. PMID- 3352789 TI - Models of normal tissue injury following combined modality therapy. PMID- 3352790 TI - Rodent model of chemoradiotherapy-induced white matter necrosis. AB - This report describes a laboratory model that permits study of the radiochemotherapy interactions in the CNS. Rats are stereotaxically implanted with a cerebroventricular cannula attached to an osmotic minipump, which slowly infuses a chemotherapeutic agent into CSF for up to 14 days. The cervical cord is irradiated, and forelimb paralysis develops 4-6 months later at an effective dose for paresis in 50% of the animals; the doses with radiotherapy alone are 2,125 cGy for a single fraction and 2,950 cGy for split fractions. Investigations with the model indicate that mature CNS tissue is not sensitized to either single fraction or split-dose irradiation with either simultaneous or post-radiation exposure to high concentrations of methotrexate. PMID- 3352791 TI - Quantitative risk of second cancer in patients in first complete remission from early stages of Hodgkin's disease. AB - Thirty-three second cancers, excluding basal cell carcinomas of skin and in situ carcinomas of the cervix uteri, were observed among 1,084 patients in first complete remission from Hodgkin's disease treated from 1964 to 1981 by the Lymphoma Group of the European Organization for Research and Treatment of Cancer and the Groupe Pierre et Marie Curie. Five of these second cancers were acute nonlymphocytic leukemias (ANLL), and five were non-Hodgkin's lymphomas (NHL). The 15-year cumulative proportion was 7.6% for second cancers; 0.7% for ANLL; and 1.2% for NHL. For solid tumors (ST) occurring in a previously irradiated area, it was 1.0% after regional radiotherapy (RT); after extended-field RT, it was 8.2% (P = .009). The relative risk (RR) of ANLL after combined chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone plus RT (relative to the general population incidence rates) was 39 (P less than .001) during the first 4-year period; it was not significantly increased in patients treated by RT without combined chemotherapy. Similar RR was observed for NHL (RR = 31; P less than .001). Moreover, an increased RR of NHL (RR = 53; P less than .001) was observed in patients treated by RT without combined chemotherapy after 10 years. For ST, no significant increased risk was observed regardless of the treatment. There is, however, a slight tendency for the risk of ST related to extended-field RT to increase after 10 years. PMID- 3352792 TI - Mechanisms of interaction between radiation and drugs with potential for improvements in therapy. PMID- 3352793 TI - Alternating chemotherapy and radiotherapy. AB - The more effective utilization of well-established chemotherapeutic agents with radiotherapy can be brought to clinical use more rapidly and with greater efficiency than can new agents. New therapeutic approaches to improving cancer treatment will most likely be coordinated with either chemotherapy or radiotherapy or combined chemotherapy and radiotherapy. The results of experimental, theoretical, and clinical studies suggest that the potential for the greatest progress over the shortest period of time in the clinical management of tumors responsive to both treatment modalities lies in the more effective interaction of well-established chemotherapeutic agents with newer radiotherapy schedules in which large amounts of radiation can be delivered between the courses of chemotherapy and temporally separated to minimize toxicity without loss of therapeutic effectiveness. The experimental and theoretical studies reinforce the basic tenets first demonstrated in the clinical management of Hodgkin's disease. This provides the medical framework for more rapidly exploiting the concepts of alternating chemotherapy and radiotherapy in tumors responsive to both treatment modalities and brings options into sharper focus. 1) Either the doses given in radiotherapy or chemotherapy can be increased or the time between treatment modalities or between courses can be decreased. 2) Experimental, theoretical, and clinical results to date provide a rational basis for clinical protocols designed to determine the most effective utilization of these two primary means of cancer management. PMID- 3352796 TI - Deutsche Gesellschaft fur Pharmakologie und Toxikologie. Abstracts, 29th spring meeting. March 8-11, 1988, Mainz. PMID- 3352794 TI - Scoring of late toxic effects--interaction of two modalities. PMID- 3352795 TI - Response of cell subpopulations in spheroids to radiation-drug combinations. AB - Chinese hamster V79 cells grown as multicell spheroids were treated with radiation and/or selected antineoplastic drugs (5-fluorouracil, cisplatin, doxorubicin, mitomycin, and carmustine) administered at equitoxic levels in defined preirradiation and postirradiation sequences. Clonogenicity of the treated cells was determined, and the results from conventional assays were compared with those from cell-selection experiments, using a fluorescence activated cell sorter, to determine the degree of interaction and regions of activity of the agents. Marked sequence-dependent differences in overall toxicity were observed; drug toxicity, spheroid reoxygenation, and direct sensitization appeared to be operative to a different extent with each drug and sequence. Maximal interaction between all drugs and radiation was, however, observed when drug exposure immediately preceded irradiation. PMID- 3352797 TI - Malignant external otitis. An unusual route to mastoiditis. PMID- 3352798 TI - Evaluation and management of selected non-neoplastic disorders of the esophagus. PMID- 3352799 TI - A Trollope is not necessarily a ho-ho. PMID- 3352800 TI - What does it take to quit smoking? PMID- 3352801 TI - Lung cancer. Relationship to active and passive smoking. PMID- 3352802 TI - How should hospital ethics committees function? Who should be included? PMID- 3352803 TI - Anorectic agents in the control of obesity. A message from the North Carolina Board of Medical Examiners. PMID- 3352804 TI - American teens and birth control. PMID- 3352805 TI - AIDS: discrimination and justice. PMID- 3352806 TI - Capitalizing on the new economics: nurse executives as catalysts for action. PMID- 3352807 TI - Organizational determinants of nurse staffing patterns. PMID- 3352808 TI - Johnson & Johnson-Wharton Fellows Program in Management for Nurses. PMID- 3352809 TI - Selecting and using a nursing consultant. PMID- 3352811 TI - Medical inflation. PMID- 3352810 TI - Nurse manager succession: the processes of taking charge. PMID- 3352813 TI - [Between reading and writing]. PMID- 3352812 TI - Production and marketing of an ethics video series. PMID- 3352814 TI - [Discoid lupus erythematosus and other clinical manifestations in female carriers of chronic granulomatous disease]. PMID- 3352815 TI - [Does something go wrong with the hands in bicycling?]. PMID- 3352818 TI - [Misunderstandings concerning the bursae of the shoulder]. PMID- 3352816 TI - [Nutritional value of meals provided in Dutch hospitals]. PMID- 3352817 TI - [Problems with high-dose estrogen/progestin combinations such as Mestrogen, in India]. PMID- 3352819 TI - [Bacterial arthritis]. PMID- 3352820 TI - [Desobstruction of the carotid artery; a retrospective study]. PMID- 3352821 TI - [Adverse effects of the state vaccination program in 1986]. PMID- 3352822 TI - [About the uroborus, the T-shirt and other affectations]. PMID- 3352823 TI - [AIDS in children]. PMID- 3352824 TI - Overlapping of functions performed by the physician and registered nurse. PMID- 3352825 TI - Current proposals for regulation of physicians' office laboratories in Nebraska. PMID- 3352827 TI - The scope of nursing practice. PMID- 3352826 TI - Avascular necrosis of bone. PMID- 3352828 TI - Persistent, non-productive cough without any demonstrable etiology. PMID- 3352829 TI - Residents' hours. PMID- 3352830 TI - False positive bone scan secondary to sympathectomy following resection of a ganglioneuroblastoma or affect of unilateral sympathectomy of bone scan in the pediatric patient. PMID- 3352832 TI - Professional liability--a societal problem. PMID- 3352831 TI - Magnetic resonance imaging in thoracic outlet syndrome. PMID- 3352833 TI - A case-control study of breast cancer in relation to oral contraceptive use in Slovenia. AB - With the aim to investigate a possible association between oral contraceptive (OC) use and breast cancer occurrence, 534 women aged 24--54 years with newly diagnosed breast cancer and 1989 individually matched hospital controls were interviewed during 1980--1983. The overall risk for ever-users vs. never-users estimated by logistic regression and adjusted for several possible confounding factors was 1.62 (p less than 0.05). The analysis of potential biases indicated that this risk may be overestimated, especially because the controls might not be fully representative of the basic population. The risk was increasing with total duration of OC use, reaching the highest value by more than 7 years of use. As to the latency, the risk was the highest for women starting pill use 4--8 years before diagnosis, thus suggesting that OCs might act as promoters rather than initiators of tumor growth. There was no substantial difference in risk between women starting pill use before 25 years of age and those starting it later. The number of users before first term pregnancy was too small to warrant relative risk estimation. Interaction (significant) was found between OC use and family history of breast cancer; there was no such evidence in other subgroups of women being at baseline breast cancer risk. There were no significant differences in the distribution of cases and controls classified by individual OC formulations used. The increased relative risk for users was concentrated in early stages of breast cancer, most likely owing to detection bias. Considering the indicated biases, the results of the study may not be quite conclusive as to the adverse effect of OCs on the breast, but they call for further investigation of this problem. PMID- 3352835 TI - Lipid peroxidation in the nuclear fraction of rat lungs induced by hydralazine. AB - Hydralazine (1-hydrazinophthalazine) was administered in drinking water as a 0.0312% solution to randomly bred female Wistar rats during 3 weeks. The average daily intake of this compound was 6.74 mg for a rat. The treatment resulted in lipid peroxidation in the nuclear fraction of the lungs. This lipid peroxidation was detected spectrophotometrically by the appearance of a peak at 233-235 nm in the spectrum of chloroform-methanol extract. The close proximity of DNA may make it a possible target for attack by free radicals. PMID- 3352834 TI - Monitoring of effects of cis-diamminedichloroplatinum (II). IV. In vivo effect of cis-diamminedichloroplatinum (II) on the function of mouse spleen cells: antibody formation and cell proliferation. AB - The effect of the cytostatic drug Platidiam (Lachema, Brno, Czechoslovakia; effective substance cis-DDP) on the primary antibody response of mouse spleen cells in tissue culture, blastic transformation of spleen cells after PHA stimulation, body and spleen weight, number of peripheral blood leukocytes, lymphocytes, polymorphonuclear leukocytes (PMNL) and reticulocytes was studied. The substance was administered to inbred C3H mice at single doses of 0.83 mg/kg, 2.5 mg/kg, and 3.35 mg/kg i.p. at time intervals of 3, 7, 14, and 21 days before testing. The weight of the mice decreased only from the third day after the dose of 3.35 mg/kg. The spleen weight was not influenced significantly. The peripheral blood leukocyte number increased on the 7th day after cytostatic application, lymphocyte number was less influenced. After cis-DDP application the ratio between lymphocytes and PMNL changed in favor of PMNL. The greatest increase of PMNL was recorded on the 7th day after cis-DDP administration. The number of nucleated spleen cells increased on the 7th day. Suppression of hematopoiesis appeared after all doses in the number of reticulocytes within 3 days, rapid regeneration from the 7th to the 14th day. The primary antibody response increased on the 3rd and 7th days, at further intervals it dropped to 20-70% in relation to the drug dose. The blastic transformation test was increased only on the 14th day after the substance application at the dose of 0.83 and 2.5 mg/kg. The dose 3.35 mg/kg suppressed the cell proliferation at all intervals tested. PMID- 3352836 TI - A study on the effect of vitamin A deficiency and supplementation on tumorigenesis in mice. AB - The effect of vitamin A deficiency and supplementation on the incidence of tumors, tumor growth and life expectancy was assessed in a murine model. Although the nature of response varied with respect to the tumor types studied, in general an increase in incidence of tumor take and further growth was noted with a concomitant fall in the survival rates in the group maintained on a vitamin A deficient diet. Supplemental vitamin A produced a prolongation of the latent period and delayed appearance of the tumor, reduced incidence and growth and improved life expectancy. Such effects seem to be mediated by a direct action of the vitamin on tumor cells, as well as through the host immune system, as revealed by nucleic acid synthetic patterns and nature of changes in the lymphocyte/neutrophil ratio, thymus weight and PHA-induced blastogenesis of peripheral lymphocytes. PMID- 3352837 TI - Some immunological parameters in Hodgkin's disease. AB - Mononuclear cells in the peripheral blood of 69 previously untreated patients with Hodgkin's disease were investigated and their changes were followed up in the course of the disease. Before the initiation of the treatment, the total number of lymphocytes, cells with ring-shaped nucleolus, E-rosette forming cells and lymphocytes with dot-like ANAE positivity were decreased and ferritin-bearing lymphocytes significantly highly increased (p less than 0.01) when compared with healthy persons. In cells of the monocyte-macrophage lineage, only the total number of cells in initial state of transformation to macrophages (active nucleolus) was significantly highly increased (p less than 0.05). In comparison with early stages, only the changes of quiet, resting cells were significantly more pronounced in advanced disease (p less than 0.01 and p less than 0.05). An excessive depression of ring-shaped nucleolus-bearing cells was associated with B symptoms. Using a discriminant analysis method, the independent influence of these cells upon the immunocompetence of the patients has been proved. After the completion of primary treatment the changes of cells were more profoundly expressed. No complete restauration of immunocompetence has been found within 1-2 years in patients responding satisfactorily to therapy. Verified by the discriminant analysis, persistent imbalance of T-lymphocyte subpopulations plays the most important role in the immune defect of patients in the second year after the therapy and later. PMID- 3352838 TI - Natural killer activity and antibody-dependent cellular cytotoxicity in patients with non-Hodgkin's lymphoma. AB - Natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood lymphocytes from untreated non-Hodgkin's lymphoma patients were found to be depressed, when tested against the human erythroblastoid cell line K562. The percentage of active killer (AK) cells and that of target binding cells (TBC) of the patients were also inhibited. Treatment of the patients lymphocytes with interferon (IFN) caused an augmentation in their NK activity which was comparable with that seen in the controls. Lymphocytes from some of the patients and controls were cocultured with K562 cells for production of natural killer cytotoxic factors (NKCF). The NKCF released by the patients lymphocytes showed a reduced lytic activity against K562 target cells. The depression in all the activities reported here showed a correlation with the clinical status of the patients except in the case of ADCC. These results indicate that further characterization of the properties of NKCF will contribute the understanding of the mechanism of NK cytotoxicity. PMID- 3352839 TI - Occurrence of carcinoembryonic antigen in tumor tissue and serum of breast cancer patients. AB - In 116 breast cancer patients, the levels of carcinoembryonic antigen (CEA) were determined before operation in the serum using RIA, and after operation in sections of breast tumor tissue using the immunohistological PAP technique. CEA circulating in the serum was found in 49 patients (42%). Elevated values (over 10 micrograms/l) were found in only 12 patients (10%). In histological specimens CEA positivity was found in 94 tumors (81%), however, in a majority of them the number of positive cells per section was low (1-10%). A comparison of positive and negative findings both in the serum and in the tumor specimens of individual patients showed that both serum and tumor sections were CEA positive in 40 patients (35%) and both localizations were CEA negative in 13 patients (12%). Although most patients had positive histological sections but negative sera (46%). Only 7% of patients had negative sections and positive sera. In 41 patients CEA could be examined both qualitatively (immunohistologically), and quantitatively in the cytosol of the same homogenized tumor. Of them, 30 patients (72%) had in the cytosol a CEA concentration exceeding 5 micrograms/g proteins, in 11 of the 41 patients (28%) no CEA was found. Immunohistological examination of CEA in this group gave positive results in 35 out of the 41 patients (85%), and only 6 tumors (15%) were completely negative. CEA was shown to be present in each histological type of the tumors studied, invasive ductal tumors being slightly more frequent and more positive than the lobular ones. No relation was observed to the structure of the tumors, nor to the degree of their differentiation. Thus, the examination of CEA levels can hardly contribute to the improvement of histological classification. PMID- 3352840 TI - Sequential development of chronic lymphocytic leukemia in a patient with polycythemia vera. AB - A patient with a seven-year history of polycythemia vera treated by repeated phlebotomies and intermittent busulfan administration developed gradually lymphocytosis accompanied by thrombocytopenia in peripheral blood and in the bone marrow. A marked pathological monoclonal proliferation of the B-cell population was detected. The sequential development of chronic lymphocytic leukemia in the patient with polycythemia vera could be considered as a coincidence because there is no reliable explanation of this event at present. PMID- 3352841 TI - Chronic lymphoproliferative disease of large granular lymphocytes. AB - An 80-year-old patient has been followed for hepato- and splenomegaly, hemolytic anemia, neutropenia with lymphocytosis with large granular lymphocyte predominance in his peripheral blood, with infiltration of bone marrow, liver and probably also spleen. Determination of surface markers of proliferating lymphocytes in peripheral blood showed a mixed phenotype of T suppressor/cytotoxic and natural killer cells (SIg-, E+, T3+, T8+, EAC+, Leu7-, N901+, NK9+, VIB C5 and VIB E3-, Ia-). An in vitro cytotoxic test showed the functional inactivity of the cells tested also after human leukocyte interferon stimulation. Chromosomal analysis neither of peripheral blood lymphocytes nor of bone marrow cells proved the monoclonality marker. Following long-term prednisone therapy, the improvement of anemia, later also neutropenia accompanied by the decrease of lymphocytes has been achieved. As the disease present in our patient was distinguished only in recent years and in our country has not been reported yet, the details on its clinical, morphologic, hematologic, cytogenetic and mainly immunophenotypic characteristics are given in this paper. The problems concerning classification of the disease and determination of its biological nature are discussed. PMID- 3352842 TI - [Prognostic significance of lacunar lesions in magnetic resonance tomography in multiple sclerosis]. AB - 175 patients with definite multiple sclerosis underwent nuclear magnetic resonance imaging. T1-weighted images showed in 59 patients (34%) periventricular lesions with a central area of decreased signal intensity. They appear as lacunar defects in the walls of the lateral ventricle system. In accordance with neuropathological findings we suggest that in these plaques a cystic degeneration has replaced gliosis. Patients with cystic defects are characterized by a high activity of the disease (e.d. increased annual production of plaques) and a poor prognosis. Lacunae are found in the early stages of the disease and provide a prognostic sign in multiple sclerosis. PMID- 3352844 TI - [Centrally-induced paradoxical innervation of the masseter muscles--an unusual cause of trismus]. PMID- 3352843 TI - [Herpes simplex encephalitis following irradiation of a brain stem glioma]. PMID- 3352845 TI - [Cretinism in empty sella syndrome]. PMID- 3352846 TI - Insulin binding and glycolytic activity in erythrocytes from dialyzed and nondialyzed uremic patients. AB - Insulin resistance in uremia has been attributed to impaired hormone-receptor binding or to postbinding defects. Oral glucose tolerance tests, insulin binding, and in vitro glycolytic activity were studied in purified red blood cells from normal control subjects (C) and from uremic patients belonging to three groups: nondialyzed (U), on chronic hemodialysis (HD), and on continuous ambulatory peritoneal dialysis (CAPD). Glucose intolerance and hyperinsulinemia were demonstrated in all groups of patients. Maximal specific binding of 125I-insulin to erythrocytes, kinetically derived receptor numbers per cell, and affinity constants for insulin binding did not differ between control and patient groups. No correlation was found between the degree of glucose intolerance and insulin binding parameters. Basal lactate production by erythrocytes incubated in vitro was significantly higher in U and HD patients than in C, whereas CAPD patients did not differ from C in this respect. Addition of 1 mM dibutyryl-cAMP and 0.5 mM isobutyl-methyl-xanthine during incubation of erythrocytes caused an increase in the rate of lactate production that was similar in magnitude in the U, HD and C groups, whereas cells from CAPD subjects showed a significantly larger absolute response to these compounds after 1 h of incubation. There was no evidence of impairment of glycolytic capacity in red blood cells from uremic patients. In addition, no correlation was found between the degree of glucose intolerance and basal or stimulated lactate production by erythrocytes. Our results obtained in human erythrocytes suggest that the insulin resistance observed in uremia does not involve a defect in hormone binding or in the intracellular capacity to utilize glucose through glycolysis. PMID- 3352847 TI - Withdrawing life support. Do families and physicians decide as patients do? AB - We studied whether families and physicians decided as patients do, in discontinuation of life-supporting treatment. We did so by comparing 66 competent patients, who themselves decided to stop dialysis to die, and 66 incompetent patients for whom families and physicians decided. We also compared comatose to demented patients and families' to physician's decision-making. There was no difference in sex, diagnosis, age, time period, decision maker (family or physician), site of residence, duration or type of dialysis, home or in-center dialysis or survival time after discontinuation. More competent than incompetent patients died at home (p less than 0.005). All incompetent patients had emerging complications, but such complications were present in only 40/60 competent patients (p less than 0.0005). In the early 1970s the physician initiated the termination of dialysis in all cases of incompetent patients; in the 1980s this had decreased to 48% (less than 0.001). No case was decided by court or hospital committee. There was no difference between comatose or demented incompetent patients, nor was there any important difference between family and physician decision-making. We believe our study indicates that substitute judgement is applied appropriately and that the decision can safely and best be left to families and physicians. PMID- 3352848 TI - Plasma levels and loss of antithrombin III in chronic ambulatory peritoneal dialysis and nephrotic patients. AB - Plasma antithrombin III (AT III) levels were measured as antigen concentration (radial immunodiffusion) and as heparin cofactor (amidolytic method) in 9 patients on continuous ambulatory peritoneal dialysis (CAPD). The loss of albumin, proteins, AT III antigen and AT III functional activity was calculated from the peritoneal dialysate and the corresponding serum levels were measured. The same determinations were performed on serum and urinary samples from 9 patients with nephrotic syndrome. Mean plasma levels of AT III antigen and AT III heparin cofactor in CAPD patients were normal, whereas nephrotic patients showed a reduction in these values within a wide range. However, the loss of AT III antigen was similar in both groups and was strictly correlated to the loss of albumin. Most AT III in the peritoneal dialysate from CAPD patients was still active, whereas in nephrotic patients only 26% of the excreted AT III was functionally active. The difference in plasma AT III was functionally active. The difference in plasma AT III levels between these two groups, in spite of the roughly similar amounts recovered in the dialysate and in the urine, might be explained by an additional AT III loss in nephrotic patients due to renal metabolism. PMID- 3352849 TI - Hexachlorobenzene and 1,1-di(4-chlorophenyl)-2,2-dichloroethene in serum of uremic patients and healthy persons: determination by capillary gas chromatography and electron capture detection. AB - The concentrations of organochlorine pesticides in serum have been determined by GC and electron capture detection. Studies were performed in 7 nondialyzed, 10 dialyzed and 6 healthy persons. Only hexachlorobenzene (HCB) and 1,1-di(4 chlorophenyl)-2,2-dichloroethene (p,p'-DDE) were consistently present. No interference by other pesticides or polychlorinated biphenyls was found by checking with GC-MS. For the nondialyzed uremic patients the average HCB concentration was 16.2 nmol/l (sigma = 6.7, n = 7), and the p,p'-DDE level 26.4 nmol/l (sigma = 31.4, n = 7). For the dialyzed uremic patients the average HCB level was 15.5 nmol/l (sigma = 11.2, n = 10) before dialysis and 17.2 nmol/l (sigma = 14.4, n = 8) after dialysis, the concentration of p,p'-DDE was 27.0 nmol/l (sigma = 38.4, n = 10) before dialysis and 28.0 nmol/l (sigma = 37.4, n = 8) after dialysis. For the healthy persons the average concentration of HCB was 7.7 nmol/l (sigma = 1.8, n = 6) and the concentration of p,p'-DDE was 20.1 nmol/l (sigma = 10.4, n = 6). HCB concentrations were significantly higher in serum of dialyzed and nondialyzed uremic patients than in controls (Wilcoxon's test). PMID- 3352850 TI - Familial medullary sponge kidney in association with congenital absence of teeth (anodontia). AB - Medullary sponge kidney was found in association with congenital absence of teeth (anodontia) in 3 siblings of a single family. Anodontia occurs in the rare familial syndrome of ectodermal dysplasia, but its association with a renal (mesodermal) anomaly is not known. The present report lends further support to a possible hereditary etiology for medullary sponge kidney. PMID- 3352851 TI - Hypouricemia due to increased tubular urate secretion. PMID- 3352853 TI - Usefulness of urinary red-cell morphology examination. PMID- 3352852 TI - Cephalosporin-induced encephalopathy in uremic patients. PMID- 3352854 TI - 'No-needle' devices for hemodialysis: is sepsis unavoidable? PMID- 3352855 TI - Glyoxylic acid in ethylene glycol poisoning. PMID- 3352856 TI - Bone aluminum intoxication: an unpreventable sequel of parathyroidectomy? PMID- 3352857 TI - Can plasmapheresis improve lupus nephritis without its immunological markers? PMID- 3352858 TI - Renal replacement therapy in Great Britain. PMID- 3352859 TI - Plasma oxalate in chronic renal failure and normal subjects: methodological problems. PMID- 3352860 TI - Simple technique for bedside peritoneal dialysis in neonates. PMID- 3352862 TI - Normal erythrocyte deformability in acute uremic rats. PMID- 3352861 TI - Negativeness of skin biopsy in dialysis amyloidosis. PMID- 3352863 TI - Carpal tunnel syndrome complicating Cimino-Brescia fistula: an electrophysiologic evaluation. PMID- 3352864 TI - Metaphit prevents locomotor activation induced by various psychostimulants and interferes with the dopaminergic system in mice. AB - Metaphit, an isothiocyanate analog of phencyclidine and a proposed phencyclidine receptor acylator, inactivated the carrier involved in the neuronal uptake of dopamine in in vitro experiments with preparations of the striatum in the mouse. In ex vivo experiments 2 and 24 hr after the intravenous administration of metaphit, no changes were observed either in the binding of [3H]cocaine to striatal membranes or in the uptake of [3H]dopamine into synaptosomes or slices. In in vivo experiments 24 hr after pretreatment with metaphit, selective labelling of uptake sites for dopamine in the striatum of the mouse with [3H]GBR 12935 was unaffected. In these in vivo experiments, however, metaphit antagonized the locomotor stimulation induced by blockers of the uptake of dopamine (methylphenidate, mazindol, cocaine, GBR 12909) but not that induced by drugs that affect locomotion by other mechanisms (amphetamine, phencyclidine). Twenty four hours after treatment with metaphit there was an increase in homovanillic acid in all regions of the brain studied (striatum, olfactory tubercle, cerebral cortex). There was no effect of metaphit on the disappearance rate of 3,4 dihydroxyphenylacetic acid and homovanillic acid from the striatum during the inhibition of monoamine oxidase with pargyline. If the increase in homovanillic acid reflected a greater rate of dopamine catabolism in metaphit-treated mice, it could explain the lack of locomotor stimulation of blockers uptake of the dopamine in these animals, resulting from a rapid breakdown of extracellularly accumulated dopamine. PMID- 3352865 TI - Selective 5-HT1B agonists identify the 5-HT autoreceptor in lumbar spinal cord of rat. AB - The purpose of the present study was to characterize the 5-HT autoreceptor in the lumbar spinal cord of the rat. The effect of selective 5-HT1A and 5-HT1B agonists on K+-evoked release of [3H]5-HT and the binding of [3H]5-HT were examined. The 5 HT1B compounds, mCPP and quipazine were more potent than exogenous 5-HT at decreasing K+-evoked release of [3H]5-HT in slices of spinal cord. The pEC40 values of 5-HT agonists tested, determined from release assays, significantly correlated with the relative affinities (pKD's) of these compounds for the binding of [3H]5-HT to the 5-HT1B receptor subtype in the presence of 2 microM 8 OHDPAT, as determined from radioligand binding studies (r = 0.98, P = 0.003). Conversely, the potencies of the 5-HT1A agonists 5-MeODMT and 8-OHDPAT, at the 5 HT autoreceptor, were negatively correlated (r = -0.77, P less than 0.10) with their potencies at displacing [3H]5-HT from the 5-HT1A subsite (binding of [3H]5 HT in the presence of 1 microM mCPP). Thus, the 5-HT autoreceptor in spinal cord appears to bear a significant pharmacological similarity to the 5-HT1B binding site. Further testing of the present results requires the development of new 5 HT1 agonists which are selective (1000-fold difference) for the 5-HT1A and 5-HT1B subsites. PMID- 3352866 TI - Administration of aspartame potentiates pentylenetetrazole- and fluorothyl induced seizures in mice. AB - An association has recently been proposed between the incidence of seizures and prolonged consumption of the phenylalanine-containing artificial sweetener, aspartame. Since consumption of aspartame, unlike dietary protein, can elevate phenylalanine in brain, and thereby inhibit the synthesis and release of neurotransmitters known to protect against seizure activity, the effect of oral doses of aspartame on the sensitivity of mice to the proconvulsant agents, pentylenetetrazole and fluorothyl was studied. Doses of aspartame were used which increased phenylalanine more than tyrosine in brain, as occurs in humans after the consumption of any dose of aspartame. Pretreatment with aspartame significantly increased the percentage of animals convulsing after administration of pentylenetetrazole and significantly lowered the CD50 for this convulsant. The average time to onset of seizures induced by fluorothyl in control mice was 510 sec; pretreatment with oral doses of 1000, 1500 and 2000 mg/kg of aspartame 1 hr earlier significantly reduced the time required to elicit seizures (394, 381 and 339 sec, respectively). The seizure-promoting effect of aspartame could be demonstrated 30, 60 or 120 min after the 1000 mg/kg dose. The seizures induced by either convulsant were potentiated by equimolar amounts of phenylalanine, a major endogenous metabolite of aspartame, while the other metabolites, aspartic acid and methanol, were without effect. Administration together with aspartame of the large neutral amino acid valine, which competes with phenylalanine for entry into the brain, completely abolished the seizure-promoting effect of aspartame.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352867 TI - Action of nootropic drugs on transcallosal responses in rats. AB - The effects of nootropic drugs and related compounds on transcallosal responses were examined in urethane-anesthetized rats. The transcallosal response was recorded from the surface of the anterior neocortex following electrical stimulation of the contralateral corpus callosum. The transcallosal response consisted of a biphasic positive-negative waveform. Hopantenate increased the amplitude of the positive- and negative-waves, without affecting the latency. Aniracetam, idebenone, bifemelane hydrochloride, TRH and meclofenoxate increased the amplitude of the negative-wave, without affecting the latencies. Vinpocetine and eburunamonine had no effect on the transcallosal response. Muscimol, amino oxyacetic acid, diazepam and pentobarbital increased the amplitude of the positive-wave and decreased the amplitude of the negative-wave, without affecting the latencies. Bicuculline and picrotoxin increased the amplitude of the negative wave, without affecting the latencies. Physostigmine decreased the amplitude of the negative-wave, without affecting the latency. Atropine was without effect. The pharmacological nature of the transcallosal response is discussed, based on findings with 16 different pharmacological agents. PMID- 3352868 TI - Behavioural and biochemical effects of haloperidol during the oestrous cycle of the rat. AB - The effects of two doses (1 and 2 mg/kg, i.p.) of haloperidol (HAL) on catalepsy, on concentrations of DA and DOPAC in frontal cortex, nucleus accumbens and striatum and on serum levels of oestradiol were investigated in intact female rats during the 4-day oestrous cycle. Catalepsy induced by haloperidol did not vary much during phases of the cycle. The turnover of DA in the cortex induced by haloperidol was significantly greater on proestrus and smaller on oestrus. The effect of haloperidol on the turnover of DA in the nucleus accumbens and in striatum was marginally affected by the oestrous cycle being greatest on oestrus. The levels of serum oestradiol were higher on proestrus and lower on oestrus. No significant differences were detected between diestrus and metestrus. After haloperidol there was a dramatic increase in serum oestradiol on oestrus, a slight increase on metestrus and diestrus and a decrease on proestrus. However, serum levels of oestradiol were not significantly different between phases of the cycle in rats treated with haloperidol. The results indicate that the oestrous cycle has a detectable influence on DAergic mechanisms in the frontal cortex and possibly in the tuberoinfudibular system, brought about by treatment with haloperidol. PMID- 3352869 TI - 5'-N-ethylcarboxamido[8-3H]adenosine binds to two different adenosine receptors in membranes from the cerebral cortex of the rat. AB - In the present study it is reported that [3H]NECA binds in a specific and saturable manner to membranes from the cerebral cortex of the rat. Scatchard analysis revealed two binding sites. The high affinity binding site (Kd 10.66 +/- 5 nM, Bmax 0.305 +/- 0.05 pmol/mg prot) was characterized by the following features: maximum binding at 25 degrees C, sensitivity to pretreatment with NEM and regulation by Gpp[NH]p, enhancing of binding in the presence of 1.0 mM MgCl2 and 1.5 mM CaCl2; the rank order of potency of several analogues of adenosine in competing with [3H]NECA for binding, was CHA greater than L-PIA greater than NECA greater than CADO. The low affinity binding site (Kd261.8 +/- 50 nM, Bmax 4.19 +/ 0.33 pmol/mg prot) showed maximum binding at 0 degrees C, insensitivity to pretreatment with NEM up to 1 mM and to regulation by Gpp[NH]p, and inhibition of binding in the presence of MgCl2 and CaCl2. The low affinity site was also present in membranes not pretreated with adenosine deaminase and, even in this condition, an IC50 of 188.5 +/- 36 nM for NECA and an IC50 of 4.35 +/- 0.20 microM for adenosine were found. It is concluded that the high affinity binding site is similar to the A1 adenosine receptors. The low affinity binding site is not classifiable among the A-type adenosine receptors, although it shows peculiar features shared both with the human platelet A2 receptor and the adenosine receptor formerly studied with [3H]adenosine in membranes from the brain of the rat; these results could reflect heterogeneity of adenosine receptors in central nervous system. PMID- 3352871 TI - Responses of anterior hypothalamic-preoptic thermosensitive neurons to locally applied capsaicin. AB - The effects of local application of capsaicin on the activity of single thermosensitive neurons in the anterior hypothalamic-preoptic area were studied in the urethane-anesthetized rat. Local injection of capsaicin through a cannula to the vicinity of the neurons increased the activity in 15 of 28 warm-units, decreased the activity in 2 of 4 cold-units and had no effect on 5 of 10 thermally-insensitive units. Electrophoretic application of capsaicin with the use of multibarrelled microelectrodes excited 16 of 27 warm-units, inhibited 12 of 17 cold-units and had no effect on 35 of 60 thermally-insensitive units. Progressive decreases in the responsiveness of the neurons to both capsaicin and the hypothalamic temperature were observed with repeated applications of capsaicin. Many neurons ceased firing after showing excitatory or inhibitory responses to single or repeated applications of capsaicin either by local injection or electrophoretic application. The results may explain the acute thermolytic response, as well as the subsequent decrease in responsiveness to the injection of capsaicin into the anterior hypothalamic-preoptic area, on the basis of changes in the activity of thermosensitive neurons in the anterior hypothalamic-preoptic area. PMID- 3352870 TI - Anti-serotonin action in combination with noradrenaline-stimulating action is important for inhibiting muricide in midbrain raphe-lesioned rats. AB - The present study was designed to examine the possible involvement of both an anti-serotonin action and a catecholamine-stimulating action in the mechanism of the inhibition of the muricide in rats with lesions of the midbrain raphe. Serotonin antagonists, such as cyproheptadine (10 mg/kg), cinanserin (10 mg/kg) and pirenperone (1 mg/kg), given alone showed little suppression of muricide in rats with raphe lesions, although the first two drugs were inhibitory at very large doses. Methamphetamine showed no inhibition of muricide at 0.32 mg/kg (i.p.), but exerted a marked inhibition of muricide when combined with the above serotonin antagonists. In addition, the dose-response curve for cyproheptadine and cinanserin was shifted markedly to the left when combined with L-threo-3,4 dihydroxyphenylserine (L-threo-DOPS) (100 mg/kg i.p.), but not with lisuride (0.32 mg/kg i.p.). Similarly, pirenperone produced a marked inhibition of muricide at doses of 0.32-1.8 mg/kg (i.p.) when combined with L-threo-DOPS, but not when combined with lisuride. These results suggest that the combination of an anti-serotonin action with noradrenergic activation is important for inhibiting muricide, at least in rats with raphe lesions. A similar mechanism also seems to be valid for the anti-muricidal effect of antidepressant drugs. PMID- 3352872 TI - Correlated effects of guanabenz on single-neuron activity in the nucleus reticularis gigantocellularis, systemic arterial pressure and heart rate in the rat. AB - The simultaneous effects of guanabenz on the activity of single-neurons in the nucleus reticularis gigantocellularis of the medulla oblongata, systemic arterial pressure and heart rate were assessed in Sprague-Dawley rats, anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Of the 35 arterial pressure-related neurons (neurons that temporally altered their spike rhythm subsequent to fluctuations in arterial pressure) which were evaluated in this reticular nucleus, 32 changed their discharge frequencies that exhibited a degree and time course parallel to the hypotension promoted by the amino-guanidine compound (5, 10 or 20 micrograms/kg, i.v.). More importantly, these alterations neuronal activity preceded the occurrence of the induced vasodepression, signifying a causative relationship between the two events. Four of the 5 non-arterial pressure-related neurons in the gigantocellular reticular nucleus, on the other hand, manifested no basic modification in their spike frequencies in relation to the hypotension induced by guanabenz. These observations provided further support for the idea that the nucleus reticularis gigantocellularis participates actively in the cardiovascular suppressive actions of the aminoguanidine compound. PMID- 3352873 TI - A study of the interaction between clonidine and morphine on analgesia and blood pressure during continuous intrathecal infusion in the rat. AB - In the rat, the continuous intrathecal (i.t.) infusion of clonidine (0.4 microgram/hr) significantly increased the tail-flick latency (TF) and the threshold for paw pressure (PP) withdrawal for 5 days and decreased the systolic blood pressure (up to 24 mm Hg) for 7 days. The antinociceptive effect of continuous intrathecal infusion of clonidine (0.4 microgram/hr) in the tail flick and paw pressure tests was not attenuated in rats that were tolerant to morphine. The acute intrathecal administration of clonidine (2.7 micrograms) and morphine (1.0 microgram) resulted in a synergistic interaction in the tail-flick and paw pressure tests. A synergistic interaction was also observed during the continuous intrathecal infusion of morphine (1.25 micrograms/hr) and clonidine (0.2 microgram/hr) in the tail-flick and paw pressure tests. Individually, these doses of morphine and clonidine had no antinociceptive effect. However, intrathecal infusion together yielded peak tail-flick and paw pressure responses comparable to that of 0.4 microgram/hr clonidine alone, without affecting systolic blood pressure. No delay in the onset of tolerance to the analgesic effect was observed with the combination as compared with clonidine (0.4 microgram/hr) alone. The data indicate that clonidine-induced spinal analgesia is independent of endogenous opioid systems linked to mu-receptors in the spinal cord, and that optimization of spinal analgesia (e.g. synergism) can be achieved during continuous intrathecal infusion without affecting cardiovascular activity. PMID- 3352874 TI - Behavioural and electrocortical changes induced by paraquat after injection in specific areas of the brain of the rat. AB - The behavioural and electrocortical effects of paraquat were studied after its administration into the substantia nigra, pars compacta, an area where dopamine (DA) containing cell bodies are present, into the caudate nucleus, where DA containing nerve endings of the DA nigro-striatal system project, into the locus coeruleus, an area containing noradrenaline cell-bodies and into the n. raphe dorsalis or into the n. raphe medianus, two nuclei containing serotonin (5-HT) cell bodies. The intraventricular administration of paraquat (10 and 50 micrograms) produced an intense pattern of behavioural stimulation and an increase in locomotor activity, circling and the wet-dog syndrome. This symptomatology was accompanied by desynchronization of the electrocorticogram (ECoG) and the appearance of bilateral high voltage epileptogenic spikes, culminating in clonic convulsions. The infusion of paraquat into the s. nigra produced contralateral head and neck deviation, behavioural and motor stimulation, these effects being observed also with smaller doses (1 and 5 micrograms), than those used intraventricularly. The ECoG activity was desynchronized and characterized by high voltage spike discharges. A similar behavioural, postural and ECoG pattern was also observed after infusion of paraquat into the caudate nucleus (10, 25 and 50 micrograms). In addition, paraquat, infused into the locus coeruleus or into the raphe nuclei (5 and 10 micrograms), produced circling, escape responses, jumping and clonic convulsions accompanied by ECoG desynchronization and epileptic phenomena. In conclusion, the present experiments showed that paraquat was able to produce central neurotoxicological effects which did not seem to be specific, at least for the doses used, for the DA nigro-striatal system. PMID- 3352875 TI - Effects of serial administration of kainic acid on the developing brain. AB - The purpose of this study was to determine whether the repeated administration of kainic acid at 24-hr intervals results in pharmacological kindling. Rather than developing an increased intensity of seizures, this method of serial administration of kainic acid resulted in the development of tolerance to its effects. PMID- 3352877 TI - Subtemporal transdural use of detachable balloons for traumatic carotid-cavernous fistulas. AB - Endovascular use of detachable balloons has revolutionized the management of carotid-cavernous fistulas so that the goals of angiographic elimination of fistula and preservation of carotid patency can usually be achieved nonsurgically. Certain circumstances of flow dynamics and anatomy, however, make an endovascular approach difficult for even an experienced interventional neuroradiologist. Fistulas involving the posterior carotid wall at its proximal cavernous entry and the anterior carotid wall in its initial horizontal intracavernous segment, as well as very low flow fistulas at other sites, have posed particular problems. Three patients with such traumatic fistulas whose endovascular treatment failed were managed by the direct transdural introduction of balloons. Intraoperative angiography was accomplished with open internal carotid artery (ICA) catheterization and the use of a portable C-arm with a 6-in. image intensifier. After temporal craniectomy and subtemporal exposure, the course of the cavernous ICA was mapped out with spinal needles and the site of the fistula was localized by intraoperative angiography. An incision was then made in the lateral wall of the cavernous sinus, and latex balloons were manually introduced via a 7 French introducer sheath. The balloons were inflated under angiographic control and detached when the fistula was obliterated. This simple technique was initially successful in three patients; the fistula was eliminated with preservation of carotid patency. One patient suffered a recurrence of his fistula 2 months postoperatively while lifting weights, and one patient developed a new 3rd nerve palsy after operation. PMID- 3352878 TI - Cavernous carotid artery aneurysm associated with Marfan's syndrome: treatment by balloon embolization therapy. AB - Intracranial aneurysms arising in the region of the cavernous carotid artery are difficult to manage surgically because of the surrounding cavernous sinus. With recent advances in microballoon technology and permanent solidification agents, it is now possible to treat certain intracranial aneurysms by detachable balloons and preserve the parent vessel. A patient with Marfan's syndrome presented with severe retroorbital pain, ophthalmoplegia, and headaches. Cerebral angiography demonstrated a large cavernous carotid artery aneurysm measuring 17 X 9 X 6 mm. This was successfully treated by placing three detachable balloons within the aneurysm and preserving the carotid artery via a transvascular approach. Intravascular detachable balloon embolization may offer a form of alternative therapy for the management of surgically difficult aneurysms. PMID- 3352876 TI - Indications for treatment and classification of 132 carotid-cavernous fistulas. AB - Classification of carotid-cavernous fistulas (CCFs) into the four types described by Barrow allows the surgeon to choose the optimal therapy for each patient. Type A patients have fast flow fistulas that are manifest by a direct connection between the internal carotid arterial siphon and the cavernous sinus through a single tear in the arterial wall. The best therapy is obliteration of the connection by a detachable balloon. Ninety-two of 95 traumatic CCFs were treated in this fashion. Direct surgical exposure of the cervical or cavernous internal carotid artery (ICA) was necessary in the remaining 3 patients, who had undergone unsuccessful surgical trapping. Three ruptured cavernous aneurysms and 2 spontaneous CCFs also had Type A connections. Other carotid-cavernous fistulas are slow flow, spontaneous dural arteriovenous malformations (AVMs) that have been classified into B, C, and D types on the basis of arterial supply. Occlusion of the ICA is not a logical choice in the treatment of dural AVMs that occur in the elderly, are relatively benign, and are often bilateral. Type B are rare and are fed by meningeal branches of the ICA only. We have not seen this type of dural fistula in our series. Type C are supplied by feeders from the external carotid only and can almost always be obliterated successfully by embolizing the external carotid artery (ECA) branches. There are 4 Type C cases in this series of 37 spontaneous CCFs. All occurred in patients less than 30 years of age and were shunts between the middle meningeal artery and the cavernous sinus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3352880 TI - Giant and multiple aneurysms of the distal posterior inferior cerebellar artery. AB - A case involving giant and multiple aneurysms of the distal posterior inferior cerebellar artery (PICA) is presented. Of the 130 reported cases of peripheral aneurysms of the PICA, 6 have been described as giant aneurysms and 5 have involved multiple aneurysms located on a single PICA. The occurrence of multiple aneurysms including one giant aneurysm has not been reported previously. A clinical description of our case as well as a review of the literature is presented. PMID- 3352879 TI - Preoperative balloon occlusion of arteriovenous malformations. AB - Many materials have been utilized to embolize cerebral arteriovenous malformations (AVMs) preoperatively. Specific vascular anatomy with large feeding vessels deep to the nidus or aneurysms within feeding arteries favor the use of detachable balloons over other embolic agents. Detachable balloons allow test occlusion of a vascular pedicle before permanent occlusion and can obliterate aneurysms in feeding arteries. We describe 36 feeder arterial balloon occlusions performed in 31 patients. Twenty-nine patients subsequently had surgical resection. None of the patients developed normal perfusion pressure breakthrough or required blood transfusions. The preoperative balloon occlusion was judged by the neurosurgeon to decrease significantly the difficulty in surgical resection of the malformation. The remaining 2 patients underwent embolization before radiosurgery. One patient had aneurysms in the feeding artery, which was balloon occluded to diminish the risk of hemorrhage. There were two neurological deficits and three asymptomatic arterial dissections related to the balloon procedure. Balloon occlusion of feeding arterial pedicles in selected cerebral AVMs may be a valuable surgical adjunct. PMID- 3352881 TI - Subarachnoid hemorrhage of unexplained cause. AB - During a 7-year period, we observed 58 patients with signs and symptoms of subarachnoid hemorrhage (SAH) in whom clinical and neuroradiological investigations failed to reveal a reasonable cause of the bleeding. Repeat panangiography was negative in the 2 patients with spasm. Rebleeding episodes soon after admission were rare, and the overall rebleeding rate was 3.4% (equivalent to an annual recurrence of 0.6%). In 1 case, a second extensive angiographic evaluation showed a small cerebral arteriovenous malformation, which was successfully treated surgically. On follow-up, 89% of the patients experienced a good outcome, with return to normal activities. This study confirms a good prognosis for patients with SAH of unknown cause. The necessity of performing a second angiographic study and the role of small infundibular dilations of the cerebral arteries are discussed. PMID- 3352882 TI - Spinal fixation after anterior decompression for symptomatic spinal metastasis. AB - Surgical strategies for the treatment of symptomatic spinal metastases must take into account both decompression of the spinal cord and stabilization of the spinal column. A method is described for securing spinal stabilization in patients who have undergone surgical decompression for symptomatic spinal metastases by an anterior approach. The fixation device used is a tailor-made prosthesis consisting of a U-shaped stainless steel plate permitting screw fixation to secure axial and rotational stability with an interposed methyl methacrylate strut to provide axial strength and support. The device has been used successfully in 51 patients who have undergone anterior decompression procedures for symptomatic spinal metastases. PMID- 3352884 TI - Central spinal cord injury: magnetic resonance imaging confirmation and operative considerations. AB - A case of central cervical spinal cord injury, confirmed by magnetic resonance imaging (MRI) and treated by myelotomy, is presented. After recovering well from his central cord syndrome and walking with assistance, the patient developed a rapidly progressive myelopathy beginning 2 months after injury. His main injury localized clinically to the C8, T1 level; but central cord abnormalities were identified 3 months after injury at the C6 level by MRI: a high signal intensity on the proton density sequence and a low-signal intensity on the T1-weighted sequence. At operation 41/2 months after his injury and 1 month after complete paraplegia, a myelotomy at C6 failed to reveal any cavity (syrinx) but instead disclosed only intense gliosis inside a slightly atrophic spinal cord. Rapid clinical improvement ensued. Secondary syringomyelia may be an endstage condition after spinal cord insults that trigger a progressive, pathophysiological reaction leading to central cord necrosis. In selected cases, myelotomy may interrupt this MRI-identified, nosogenic process before cavitation has occurred. PMID- 3352883 TI - Indomethacin and dexamethasone treatment in experimental neoplastic spinal cord compression: Part 1. Effect on water content and specific gravity. AB - Water content and specific gravity were measured in the cervical, high thoracic, thoracic, and lumbar segments in an experimental model of neoplastic epidural spinal cord compression in rats harboring a thoracolumbar tumor. Increased content of water was observed only in the compressed lumbar cord segments of paralyzed rats (P less than 0.04). A progressive increase in specific gravity values of the compressed segments accompanied the increasing severity of neurological dysfunction (P less than 0.003 in paraplegic rats). Electron microscopy of the compressed cord revealed enlarged interstitial spaces, myelin breakdown, and extravasated blood cellular elements. Treatment with dexamethasone (10 mg/kg q 12 hr x 3) failed to reduce the increased content of water, but corrected specific gravity changes. Treatment with indomethacin (10 mg/kg q 12 hr x 3) reduced both elevated water content and specific gravity values back to normal levels. In untreated animals, the interval between the first neurological sign (limp tail) and paraplegia was 2.8 +/- 0.34 days (mean +/- SE). Treatment with dexamethasone lengthened this period by 28.6% (P less than 0.05); treatment with indomethacin lengthened it by 66.4% (P less than 0.005). We conclude that, because the specific gravity measurements in this model reflect complex pathophysiological processes, their translation into water content values is not advisable. Pharmacological intervention with indomethacin compares favorably with dexamethasone in reduction of spinal cord edema and in delaying the onset of paraplegia. PMID- 3352885 TI - Serious complications of microvascular decompression operations for trigeminal neuralgia and hemifacial spasm. AB - Serious complications of microvascular decompression operations for trigeminal neuralgia or hemifacial spasm are reported. Among 278 patients who underwent microvascular decompression, 9 serious complications were observed: 1 intracerebellar hematoma with acute hydrocephalus, 1 cerebellar swelling with acute hydrocephalus, 1 supratentorial acute subdural hematoma, 2 status epilepticus, 1 infarction of the brain stem, 1 subarachnoid hemorrhage due to traumatic aneurysm, and 1 infarction in the territory of the posterior cerebral artery. Of the 9 patients with such complications, 2 died. The possible causes of such serious complications are discussed. PMID- 3352888 TI - Dorsal root entry zone lesions for the treatment of brachial plexus avulsion injuries: a follow-up study. AB - Dorsal root entry zone (DREZ) lesions have been shown to yield short term relief from the pain associated with a brachial plexus avulsion injury. Because of the propensity of pain to recur after neuroablative procedures, 39 patients with pain after a brachial plexus avulsion injury were observed for 14 months to 10 years after DREZ lesions were made. Fifty-four per cent of these patients were afforded good pain relief. Of 21 patients who had multiple small lesions made within the DREZ, 15 (72%) were afforded good pain relief. PMID- 3352887 TI - Diagnosis and surgical treatment of spasmodic torticollis of 11th nerve origin. AB - Of 22 patients with spasmodic torticollis, 7 were treated by microsurgical decompression of the 11th nerve. In these patients, there was an intermittent horizontal torticollis characterized by aggravation of the symptoms when in a resting posture, presenting with a striking contrast to the torticollis of extrapyramidal origin that was alleviated while in the resting posture and aggravated by postural stress. A tight neurovascular contact was observed at the C1 level, occurring between the principal 11th nerve and the vertebral or posterior inferior cerebellar artery. Nerve decompression was achieved in 2 by transposing the compressing artery and in 5 by sectioning at C1 or C2 the branching root of the 11th nerve that had caused the tight cross contact by locking the nerve trunk to the dura mater. The symptoms had improved after an interval of 1 to 4 weeks. After an average follow-up of 3 years, full or satisfactory relief had been obtained in 5 and some improvement had occurred in 2 patients. Possible neural mechanisms related to torticollis of 11th nerve origin are discussed. PMID- 3352886 TI - Use of perioperative steroids with microvascular decompression operations. AB - Complications associated with the use of perioperative steroids in elective craniotomies were evaluated in a single-blind prospective study of 222 consecutive microvascular decompression operations. Patients were randomized into one of three groups: Group A received steroids preoperatively and for 4 days postoperatively, Group B received steroids pre- and postoperatively for 1 day, and Group C received no steroids. There were 17 complications in Group A; 12 of these were wound-related. There were significantly fewer complications in Groups B and C (P less than 0.01). Group B had 3 complications, Group C had 4, and there was only 1 wound-related complication in Group C. There were no deaths, deep wound infections, or life-threatening complications. Severe postoperative headaches, a symptom that steroids were intended to minimize, occurred in 38% of patients in Group A, 42% of patients in Group B, and 25% of patients in Group C. The use of perioperative steroids did not reduce the length of postoperative hospitalization. Duration of the operation had no significant effect on the incidence of postoperative complications or the length of postoperative hospitalization. We conclude that there is no indication for the routine perioperative use of steroids with microvascular decompression operations of the posterior fossa cranial nerves and that such use leads to a higher incidence of postoperative complications. PMID- 3352889 TI - Return of gonadal function with resection of nonfunctioning pituitary adenoma. AB - A 42-year-old man with severe testicular failure (testosterone 24 ng/dl, normal 300-1100) was found to have a nonfunctioning chromophobe pituitary adenoma. Resection of the pituitary tumor resulted in recovery of gonadal function (testosterone 359 ng/dl). Hypogonadism caused by pituitary adenomas is usually attributed to either hyperprolactinemia or irreversible destruction of normal pituitary tissue, neither of which is applicable to this patient. The recovery of our patient's gonadal function after operation suggests that a reversible compression of viable tissue or impairment of hypothalamic-pituitary communications was responsible for his endocrine deficiency. PMID- 3352890 TI - Predictive value of temporary external lumbar drainage in normal pressure hydrocephalus. AB - In a prospective study on the effect of shunting, 22 patients diagnosed as suffering from normal pressure hydrocephalus (NPH) were investigated by means of temporary external lumbar drainage (ELD). Five patients had to be excluded from the study because of complications of ELD or definitive shunting. ELD correctly predicted the outcome of shunting in all of the remaining 17 patients. The value of external lumbar drainage in NPH is discussed on the basis of personal experience and data from the literature. It seems to be a safe and valuable tool for predicting the outcome of definitive shunting procedures. PMID- 3352891 TI - Relationships among cortical ischemia, infarction, and hemorrhage in eclampsia. AB - Cerebral infarction and hemorrhage are well-known cerebrovascular complications of eclampsia. A 30-year-old woman with eclampsia developed bilateral posterior parietal and occipital hemorrhages 4 hours after computed tomography demonstrated lucencies indicative of ischemia or infarction within the same regions. The association between infarction and hemorrhage has not been previously documented by computed tomography in eclampsia. Review of the pathophysiological mechanisms and associated risk factors has prompted a more aggressive prophylactic therapeutic approach. PMID- 3352892 TI - Acute subdural hematoma associated with nontraumatic middle meningeal artery aneurysm: case report. AB - A rare case of acute subdural hematoma from rupture of a nontraumatic aneurysm of the middle meningeal artery is described. The subdural hematoma was evacuated and the aneurysm was removed. The literature on nontraumatic aneurysm of the middle meningeal artery is reviewed. The importance of cerebral angiography in the patient with an unexplained subdural hematoma is emphasized. PMID- 3352893 TI - Cervical root compression by a traumatic pseudoaneurysm of the vertebral artery: case report. AB - We report the case of a patient with cervical monoradiculopathy secondary to a pseudoaneurysm of the vertebral artery caused by a knife wound to the neck. PMID- 3352894 TI - Intraspinal schwannoma presenting solely with rectal pain. AB - A cauda equina schwannoma presented solely with rectal pain. The tumor was found to have infarcted and hemorrhaged. A discussion of rectal pain is included, and it is speculated that some forms of rectal pain, especially those classified as proctalgia fugax or rectal neuralgia, may be due to cauda equina tumors. PMID- 3352895 TI - Amyloidoma of the cervical spine: a case report. AB - This is the first published report of an amyloidoma localized to the cervical spine. Primary amyloidosis of bone is rare. Only 5 cases involving the spine have been described. We present a 74-year-old man with cervical and occipital radicular pain as the manifestations of an amyloidoma involving the 2nd cervical vertebra. The signs and symptoms of this disease, when localized to the vertebrae, are nonspecific and result from bony destruction and compression of neural structures. Diagnosis requires a high index of suspicion and, ultimately, adequate tissue biopsy for histopathological studies. Curative resection is possible for well-localized lesions. Additionally, external immobilization with a halo vest and bony grafting for fusion may be indicated when the cervical spine is involved. PMID- 3352896 TI - Pleomorphic xanthoastrocytoma: report of two cases. AB - Two cases of pleomorphic xanthoastrocytoma are presented to draw attention to this relatively benign variant of glioma. The circumscribed tumors, each with a cystic component, were located superficially, one in the mesial right temporal lobe and one in the right temporoparietal region. The patients were aged 12 and 14 years, and it is now almost 7 years since the onset of symptoms in the 12-year old boy. The optimal plan of management is discussed. PMID- 3352897 TI - Malignant transformation in craniopharyngioma. AB - Malignant transformation in a craniopharyngioma has not been described previously. A 49-year-old woman presented with recurrence of a suprasellar craniopharyngioma diagnosed 35 years previously. The patient had been treated surgically for recurrence on five occasions. Radiation therapy had been administered 7 years before the final presentation. Tissue obtained from the fifth operation revealed malignant degeneration in a typical craniopharyngioma. PMID- 3352898 TI - Use of Halifax interlaminar clamps for posterior C1-C2 arthrodesis. AB - Eight patients with atlantoaxial instability secondary to trauma or rheumatoid arthritis were treated with posterior C1-C2 arthrodesis using the Halifax interlaminar clamp and autogenous bone graft or methylmethacrylate. Thus far, with an average follow-up of 6 months, satisfactory stability has been achieved with no instrument failure. PMID- 3352900 TI - Conversion of a lumboperitoneal shunt to a lumboatrial shunt through femoral catheterization: technical note. AB - A new technique for the diversion of the peritoneal end of a lumboperitoneal shunt into the right atrium through femoral vein catheterization is presented. As an alternative to a ventriculoatrial shunt, this is a promising technique for the treatment of patients with communicating hydrocephalus when the peritoneal cavity is not suitable for placing the distal end of the shunt. PMID- 3352899 TI - Technical note: the removal of free peritoneal catheters in the revision of ventriculoperitoneal shunts. AB - The widespread usage of ventriculoperitoneal shunts has been followed by a plethora of complications. One of these complications, the separation and migration of the distal tubing to be free intraperitoneally, has been relatively disregarded in the literature both as a phenomenon and as to treatment. We present our experience with nine such cases, four involving two peritoneal catheters. Unless contraindicated, we think that such tubing should be removed during shunt revision by single digit blind palpation of the tubing. No complications arose from this procedure, and the postoperative course was uneventful. The indications for this procedure are discussed in relation to the relevant literature. PMID- 3352901 TI - Removal of malignant astrocytomas. PMID- 3352902 TI - Seronegative myasthenia gravis. AB - Of 221 patients with myasthenia gravis, 18.5% had no detectable antibodies to acetylcholine receptor. Seven of 14 patients (50%) with only ocular symptoms for more than 2 years were seronegative, and 25 of 145 (17%) patients with generalized myasthenia were seronegative. The clinical characteristics of seronegative patients did not differ from patients with high antibody titers. No seronegative patient had a thymoma, but that difference did not reach statistical significance. Lack of serum antibodies did not preclude favorable response to thymectomy or plasmapheresis. PMID- 3352903 TI - Focal task-specific tremor and dystonia: categorization of occupational movement disorders. AB - We studied 28 patients with focal task-specific disorders. Three groups were identified, according to the occurrence of focal tremor alone (group I, n = 10), dystonia alone (group II, n = 8), and tremor-dystonia combination (group III, n = 10). Four of six patients in groups I and III showed improvement with beta blocking agents alone, and another patient improved with primidone and metoprolol. Four of seven patients in groups II and III improved at least moderately with only anticholinergic medication. The coexistence of focal tremor and focal dystonia in the same limb in 10 patients (group III) suggests a link between these focal disorders. We conclude that focal tremor and focal dystonia are related to generalized essential tremor and generalized dystonia. A scheme which conceptualizes these interrelationships is proposed. PMID- 3352904 TI - Hemiparkinsonism with hemiatrophy. AB - We studied fifteen patients with hemiparkinsonism and ipsilateral hemiatrophy (HP/HA) to better characterize the clinical features of this syndrome and its rate of progression. Patients were distinguished by highly asymmetric parkinsonism with predominant signs on the side of HA, early age of onset (43.7 years versus 60.2 years in our control population of idiopathic Parkinson's disease [IPD], abnormal birth history (7/15), and dystonia occurring prior to levodopa therapy (10/15). In six patients, the mean duration of disease until the initiation of levodopa therapy was 14.2 years, as compared with 4.1 years in our control population of IPD. The slow progression of disease underscores the relatively favorable prognostic significance of HP/HA and its distinction from IPD. PMID- 3352905 TI - The clinical course of spasmodic torticollis. AB - Among 24 of 36 patients with idiopathic spasmodic torticollis referred to one of us over a 10-year period, who were followed up for more than 1 year, we defined three outcome groups. Three patients (13%) underwent complete or almost complete remission at a median of 3.0 years into the illness. Eight patients (33%) had partial remissions, which tended to occur somewhat later than the first group. The remaining 13 patients had no significant improvement in their disease; they were more likely to be older at the onset of the illness, develop constant rather than intermittent neck deviation, and have a "geste antagonistique." As a whole, the study population was exposed to a wide variety of therapeutic interventions that had little, if any, obvious clinical effect. PMID- 3352907 TI - Role of motor performance in cognitive processes of parkinsonian patients. AB - Sixty-seven parkinsonian patients and 44 control subjects were tested for cognitive function and motor performance, using reaction times and movement times. Parkinsonian subjects did significantly worse in tests that required visuoperceptual and perceptual motor abilities, such as Object Assembly, Block Design, and Zazzo's test. Analysis of covariance of test scores showed that Block Design and Object Assembly scores were not significantly different between patients and controls when adjusted for reaction and movement times. Also, reaction and movement times were more delayed in parkinsonian patients than in controls. These results stress the main role of motor dysfunction in visuospatial and perceptual motor impairment. PMID- 3352906 TI - Clinical significance of the relationship between O-methyldopa levels and levodopa intake. AB - A recent clinical trial of controlled-release carbidopa/levodopa preparation afforded us the opportunity to examine the effects of chronically increasing circulating 3-O-methyldopa (OMD) levels on the clinical response to levodopa. In patients taking standard Sinemet, both mean plasma OMD levels and the area under the plasma concentration-versus-time curve (AUC) obtained during 8-hour periods of blood sampling correlated highly with the total daily intake of levodopa. In patients taking the controlled-release formulation, the mean daily intake of levodopa was doubled. This, in turn, led to a doubling of the mean OMD level and its AUC, whereas the AUC for levodopa was unchanged. Despite the increase in circulating OMD there was no reduction in mobility in either the "on" or "off" conditions. Thus, doubling plasma OMD levels did not seem to interfere with brain uptake of levodopa sufficiently to cause a deterioration in its therapeutic efficacy in these patients. PMID- 3352908 TI - Axial versus distal motor impairment in Parkinson's disease. AB - We measured axial (head rotation) and distal (wrist flexion and extension) movements in parkinsonian patients with varying stages of disability, before and after administration of L-dopa. Velocities for both movements were proportionately reduced in all stages of disease. L-Dopa administration provided a small but consistent increase in distal movement velocity for most patients, whereas in patients with advanced disease (stages III to V), axial movement velocity actually declined after administration of L-dopa. This decline may be partially responsible for the failure of L-dopa administration to reverse the loss of "righting reflexes" in these patients. Measurement of axial motor control may be a useful tool in evaluating therapeutics for Parkinson's disease patients. PMID- 3352909 TI - Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication. AB - Manganese (Mn) poisoning, a well-known hazard in miners and industrial workers, shares many features with Parkinson's disease. Two young agricultural workers with a parkinsonian syndrome, who mentioned exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate), led us to investigate a new possible source of Mn intoxication. Fifty male rural workers with occupational exposure to maneb were compared with 19 rural workers without fungicide exposure. We noted significantly higher prevalence of plastic rigidity with cogwheel phenomenon, headache, fatigue, nervousness, memory complaints, and sleepiness in the exposed group. In addition, we saw other neurologic signs, such as postural tremor, cerebellar signs, and bradykinesia, although without statistical significance. The data suggest that occupational exposure to pesticides containing Mn is a possible source of Mn intoxication of the CNS. PMID- 3352910 TI - Ambulatory EEG recordings in epileptic and nonepileptic children. AB - We examined the cassette-recorded 24-hour ambulatory EEG findings in children who had either clinically definite seizures or episodic behavioral disturbances not regarded as epileptic on clinical grounds. Among 40 epileptic patients, 22 had one or more attacks during the 24-hour recording session. In 15 of these patients all clinical attacks had appropriate ictal electrographic accompaniments; in another 6 some (but not all) attacks did so. Among 55 children with nonepileptic spells clinically, the 24-hour recording was uninterpretable for technical reasons in one, and in 30 it provided no relevant information because there were no recorded clinical or electrographic attacks. In the remaining 24 patients, one or more clinical attacks were captured, and in no instance was there any accompanying electrographic change. Our findings indicate that the absence of ictal EEG changes during attacks cannot be used in isolation to make a diagnosis of pseudoseizures, but support such a diagnosis made on clinical grounds. The more important role of the ambulatory EEG is to exclude a diagnosis of nonepileptic attacks by demonstrating electrographic seizure activity accompanying typical clinical attacks. Whether the technique will have a useful role in the evaluation of patients when the nature of an episodic disturbance of cerebral function is unclear clinically remains to be established, but will require long-term follow-up to validate any conclusions reached by the electrophysiologic technique. PMID- 3352911 TI - Leptomeningeal dissemination of low-grade gliomas in childhood. AB - Although leptomeningeal spread (LMS) of primary CNS tumors in children has been well documented in the literature, it has rarely been reported in children with low-grade gliomas. Between 1975 and 1985, 6 of 162 children (3.7%) with low-grade gliomas treated at Children's Hospital of Philadelphia had LMS. LMS was present at diagnosis of the original tumor in one patient, was the first sign of relapse in one patient, occurred simultaneously with local relapse in two patients, and after local relapse in two patients. Pathology of the original tumor was low grade astrocytoma in five and low-grade oligodendroglioma in one. Primary tumor site was cervical cord in three, chiasm in one, frontal lobe in one, and cerebellum in one. All of the children with LMS had undergone surgical treatment at the time of diagnosis of the primary tumor; four had total resections at some point in their course. Three of the six patients died; three are still alive after treatment with radiation therapy and/or chemotherapy. The longest survival to date has been 3 1/2 years after diagnosis of LMS. We compared clinical characteristics of these six patients with 131 children with low-grade tumors without dissemination treated at our institution during the same time period. LMS, although relatively infrequent, does occur in children with low-grade gliomas, especially spinal cord tumors. LMS may occur at any time during illness and diagnosis may be difficult unless LMS is suspected. Treatment, at times, results in clinical improvement and considerable disease control. PMID- 3352912 TI - Cognitive impairment and sensory loss associated with chronic low-level ethylene oxide exposure. AB - A 29-year-old college graduate worked for 10 years adjacent to an ethylene oxide (EtO) chemical sterilizer. When the sterilizer was closed, levels of EtO in the air around the sterilizer were 4.2 ppm (OSHA maximum level, 1 ppm). Seven years after beginning work with EtO, she experienced impaired memory, increased irritability, clumsiness, and falling. Three years later exposure ceased, and symptoms markedly improved over the next few months, but did not disappear entirely. Neurologic and neuropsychological exams 1 year after exposure ceased demonstrated emotional lability, impaired concentration, cognitive slowing, impaired recent and remote memory, and impaired thermal and vibratory sense in distal limbs. Her pattern of relatively preserved learning and profound forgetting distinguished her from most other subjects with memory disorders. No other causes for the condition were identified. PMID- 3352913 TI - Hereditary branchial myoclonus with spastic paraparesis and cerebellar ataxia: a new autosomal dominant disorder. AB - We report a family with branchial myoclonus, spastic paraparesis, and cerebellar ataxia in which six members were affected in two generations and the inheritance appeared to be autosomal dominant. Age at onset ranged from 40 to 50 years. Rhythmic myoclonus involving the palate, pharynx, larynx, and face was followed by truncal ataxia and spastic paraparesis in most patients. CT and MRI revealed mild atrophy of the cerebral and cerebellar cortex and severe atrophy of the medulla and spinal cord. The pons appeared normal and the olives not hypertrophic. CSF studies revealed severe reduction of the serotonin metabolite 5 hydroxyindoleacetic acid. Treatment with 5-hydroxytryptophan and carbidopa at highest tolerated dose mildly improved ataxia but did not modify the myoclonus. Treatment with anticholinergics, benzodiazepines, phenytoin, valproate, carbamazepine, and baclofen was unsuccessful. The clinical symptoms were progressive, leading to death or severe disability 5 to 10 years after the onset of the disease. PMID- 3352915 TI - Myasthenia gravis and primary squamous cell carcinoma of the thymus: a case report. AB - We detail a case of primary squamous cell carcinoma of the thymus in a patient with myasthenia gravis. The clinical course of the patient and the gross and histologic appearance of the thymus are discussed. Appropriate therapy for patients with these tumors includes resection of the tumor followed by radiation therapy and continued surveillance for recurrence. Review of the literature indicates less than 50% survival at 10 years and 22% recurrence rate at 5 years for patients with this tumor. PMID- 3352916 TI - Neuropsychological and behavioral abnormalities in an adolescent with frontal lobe seizures. AB - A 13-year-old girl had a reversible frontal syndrome secondary to partial complex seizures. She developed sudden and dramatic behavioral changes including sexual disinhibition, loss of concern for personal hygiene, physical and verbal aggression, and pressured and tangential speech. Although the basic neurologic examination was normal, neuropsychological testing revealed selective impairment on tasks sensitive to frontal dysfunction with relatively normal performance on other tests. This case demonstrates that a frontal syndrome can be caused by partial complex seizures and that behavior comparable to that observed in adults with frontal dysfunction may occur in young adolescents. PMID- 3352914 TI - Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy). AB - We report a large French-Canadian kindred with 33 affected members in six generations showing early-onset autosomal dominant limb-girdle myopathy and contractures. This myopathy is unique because of its benign course, with many members only minimally impaired even in old age. Examination of affected members revealed mild to moderate proximal weakness and wasting. Contractures were observed at the elbows and ankles in all, while in some they were more widespread. Serum CK was either normal or slightly raised, and electrodiagnostic studies suggested a primary myopathy. Muscle biopsy revealed nonspecific features of a myopathy without fiber necrosis or regeneration. Cardiac involvement was absent clinically in all patients and at autopsy in two affected individuals. The similarities between four previously reported families and our own establishes this myopathy as a distinct clinicogenetic entity, for which we propose the name "Bethlem myopathy." PMID- 3352917 TI - Rare Ha-ras and c-mos alleles in patients with intracranial tumors. AB - The occurrence of rare hypervariable Ha-ras alleles or of a rare c-mos allele in white blood cell DNA is claimed to be associated with susceptibility to cancer. We analyzed a group of patients with intracranial tumors to determine whether the occurrence of rare alleles at the Ha-ras locus and at the c-mos locus was increased in comparison with normal individuals. We found a higher incidence of rare hypervariable Ha-ras alleles (9.5% to 3%) and a 5 kilobase EcoRI c-mos allele (2.5% to 0%) in the patients. These results are consistent with the opinion that such unusual alleles are associated with a predisposition to intracranial tumors. PMID- 3352918 TI - Ischemic stroke associated with methamphetamine inhalation. AB - Intracranial hemorrhage and ischemic stroke have been reported to complicate oral or intravenous use of methamphetamine. We report three cases of ischemic stroke following methamphetamine inhalation. PMID- 3352919 TI - Epidemiology of multiple sclerosis in London and Middlesex County, Ontario, Canada. AB - A case-controlled epidemiologic study of multiple sclerosis (MS) was carried out in London, Ontario, and its surrounding Middlesex County for the period 1974 1983. The prevalence rates for clinically definite/probable MS on January 1, 1984 were 94/100,000 for the city and 91/100,000 for the county. The estimated annual incidence rate for the decade 1974-83 was 3.4/100,000. The female-to-male sex ratio was 2.5:1. A familial history of MS was recorded in 14.4% of close relatives and a total of 17% when distant relatives are included. The MS group is predominantly of British (70%) and European (23%) origin. The urban-rural residence pattern analysis indicates no significant regional influence on the risk of developing MS. PMID- 3352921 TI - Intracerebral hemorrhage revisited. PMID- 3352920 TI - Multiple sclerosis in Saudi Arabia. AB - There are indications of increasing incidence of MS in Saudi Arabia. Of 806 neurology inpatients, 16 had MS, 21 myasthenia gravis, and 10 amyotrophic lateral sclerosis, with a ratio of 1:1.3:0.6, respectively. The symptomatology and site of lesions are similar to that seen in the West, but the course and evolution might be different. The main course was remissions and relapses but without transformation to chronic progressive disease, and the main disability was partial or complete bilateral visual loss, seen in 19% of the patients. PMID- 3352923 TI - Seizures induced by exercise. AB - Three patients had a clinical history of epileptic seizures during exercise. In all three patients, generalized epileptiform EEG abnormalities were activated by exercise, whereas none had paroxysms during resting wakefulness or during hyperventilation, and only one had a paroxysmal discharge during sleep. Advice to epileptic patients about physical activity should be based on a careful history of individual tolerance. In doubtful cases, an EEG recorded during exercise can provide evidence for an epileptic mechanism. PMID- 3352922 TI - Carrier drugs. Presidential address American Academy of Neurology, 1987. PMID- 3352924 TI - Ictal speech, postictal language dysfunction, and seizure lateralization. AB - In 84 patients with complex partial seizures evaluated by EEG and video telemetry, who went on to have seizure surgery, complex intraictal vocalizations and postictal language dysfunction were found to have strong lateralizing significance. Thirteen patients had ictal speech, and 12 of these had right-sided seizure foci. Twenty-eight had intact postictal language, and 21 of these had right-sided foci. Of the 32 with impaired postictal language, 21 had left-sided foci. PMID- 3352925 TI - Familial parkinsonism, apathy, weight loss, and central hypoventilation: successful long-term management. AB - We report a third family with six members with features of the syndrome of familial parkinsonism, depression, weight loss, and central hypoventilation. Patients with this syndrome typically die suddenly, presumably from central respiratory failure. Following multiple respiratory arrests, one affected member was successfully managed with aggressive pulmonary care, tracheostomy, and intermittent home mechanical ventilation, which, combined with carbidopa/levodopa, allowed for a functional lifestyle with improvement in apathy, mobility, and nutritional status. PMID- 3352927 TI - Comparison of the prevalence of Parkinson's disease in black populations in the rural United States and in rural Nigeria: door-to-door community studies. AB - A door-to-door survey of Parkinson's disease (PD) in Copiah County, Mississippi, using a pretested screening procedure (with a high sensitivity for detecting PD), followed by examination of all positives by a senior neurologist, revealed similar prevalence ratios for blacks and whites. The same procedure was applied in the community of Igbo-Ora, Nigeria, a black population of West Africa. To assure uniformity in the procedures and application of the diagnostic criteria, a neurologist from each survey site visited the other site. Among a black population of 3,521 over age 39 in Copiah County, there were 12 cases of PD, with an age-adjusted prevalence ratio of 341/100,000. The comparable figures for Igbo Ora were as follows: population over age 39 = 3,412; cases of PD = 2; age adjusted prevalence ratio = 67/100,000. PMID- 3352926 TI - Phenobarbital does not alter phenytoin steady-state serum concentration or pharmacokinetics. AB - Phenytoin pharmacokinetics and biotransformation were studied with stable isotope tracer techniques in six patients before and after addition of phenobarbital. No significant (p less than 0.05) changes in phenytoin serum concentration, clearance, elimination half-life, volume of distribution, or clearance via production of p-hydroxyphenyl-phenylhydantoin or phenytoin dihydrodiol occurred after addition of phenobarbital. Thus, frequent phenytoin serum concentration determinations or a change in phenytoin dosing rate are probably not necessary after adding phenobarbital. PMID- 3352928 TI - Compulsive pre-sleep behavior and apathy due to bilateral thalamic stroke: response to bromocriptine. AB - A 38-year-old women with bilateral thalamic infarctions had a severe memory disorder, severe apathy, and a compulsive tendency to assume a sleeping position. Bromocriptine improved the apathy and the disinhibited pre-sleep behavior. PMID- 3352930 TI - Hydromyelia associated with arrested hydrocephalus. AB - A 16-year-old male with a 9-year history of spontaneously arrested hydrocephalus was noted to have hydrosyringomyelia and increased intracranial pressure shortly after sustaining minor head trauma. His symptoms resolved completely following ventriculoperitoneal shunt replacement. Hydrosyringomyelia may occur in the setting of long-standing, apparently arrested hydrocephalus. PMID- 3352929 TI - Lack of efficacy of phosphatidylcholine in ataxias. AB - We gave phosphatidylcholine orally at a daily dosage of 9 grams for 4 years to 20 subjects with Friedreich's ataxia (FA) and 24 with olivopontocerebellar atrophy (OPCA). There was no clinical improvement during the follow-up compared with 12 ataxic patients (six FA and six OPCA) who did not receive any treatment. A 6 month trial at a double dose did not have any significant effect. This study indicates that phosphatidylcholine does not change the natural course of ataxias. PMID- 3352931 TI - Asterixis mimicking drop attacks in chronic renal failure. PMID- 3352932 TI - Cortical innervation of forehead. PMID- 3352933 TI - Microsaccades and vision. PMID- 3352934 TI - Central and peripheral demyelinization. PMID- 3352935 TI - Torsion dystonia. PMID- 3352936 TI - Thoraco-abdominal aortic approach for the treatment of pararenal aneurysm. AB - The results of a thoraco-abdominal retroperitoneal approach for the treatment of pararenal aneurysms are discussed. Fifteen patients with juxtarenal (7 pts) and suprarenal (8 pts) aneurysms were operated on by a left side thoracolaparotomy with retrocolic dissection. In 12 patients suprarenal aortic cross clamping was necessary for 10 to 60 minutes. Seven tube and eight bifurcation grafts were implanted using the inlay technique. There were no postoperative deaths; only one patient had a severe complication with total renal failure for which hemodialysis was started. In our experience the thoraco-abdominal aortic approach is a safe method for the treatment of patients with pararenal aneurysm. PMID- 3352937 TI - Decreased venous outflow without venous obstruction--an analysis of three cases. AB - Three patients without prior thrombosis or varicosities presented with decreased venous outflow. They suffered from venous complaints, such as oedema and pain in the leg after prolonged standing. Phlebograms showed no obstruction or hypoplasia. Normal function of calf muscle pump and valves was present at venous pressure determination. The theoretical basis of venous emptying is discussed and a hypothesis is postulated that decreased emptying is due to a change in elastic properties of the venous vessel wall. PMID- 3352938 TI - Tissue expansion in reconstructive surgery. AB - A surplus of skin for closure of a defect can be obtained by gradual filling of a subcutaneous balloon. In this way reconstruction of extensive skin defects with neighbouring skin is possible. Two patients with skin defects of the head are illustrative for this expansion technique. The technique, indications and histology are discussed. PMID- 3352939 TI - Gross abdominal distension in a neonate. PMID- 3352940 TI - Thoracic outlet syndrome after corrective surgery for pectus excavatum. AB - Two patients are described who developed a thoracic outlet syndrome (TOS) after undergoing Ravitch's operation for the correction of pectus excavatum. In one case the syndrome developed a few days after surgery, whereas in the second patient it manifested more gradually. A third patient presented with latent TOS and pectus excavatum. It is recommended that prior to the correction of pectus excavatum, the patient should be examined to detect signs of neurovascular compression due to latent thoracic outlet syndrome. After surgery the possibility of this complication should be kept in mind to avoid permanent lesions of the cervicobrachial plexus. PMID- 3352941 TI - Actinomycosis of the gallbladder. AB - Actinomycosis is a chronic suppurative infection usually caused by Actinomyces israeli. It is rarely located in the gallbladder and, if so, it can masquerade as a chronic cholecystitis. The case history of a 54-year-old female patient with actinomycosis of the gallbladder is described, and a survey of the literature is given. Although surgical drainage is the initial treatment of choice, a prolonged postoperative antibiotic treatment is advocated. PMID- 3352942 TI - Artificial pleuroperitoneal shunting. PMID- 3352943 TI - [Respiratory function evaluation in esophageal surgery. Predictive value of tests]. AB - In the context of major surgery the predictive significance of respiratory function tests in relation to postoperative pleuro-pulmonary complications is assessed. A statistical analysis is performed on a series of 85 oesophagectomy after thoracotomy and laparotomy. The most significant respiratory function indices are found to be those relating to volume restriction and the Mottley index. PMID- 3352944 TI - [Macrocytosis in relation to the severity of the hepatopathy]. AB - Among factors causing the hepatopath's relative erythrocyte macrocytosis, the influence of alcohol and liver function damage was compared. Hepatopathic macrocytosis is different from Biermer's macrocytosis and evidently involves different pathogenetic mechanisms. It is significant that a deficit in vit. B12 does not occur and a modest deficit in folates only rarely. There is much evidence of an alteration in lipidemia and particularly in apo-protein content. It is concluded that the two factors considered have different mechanisms but produce the same results. PMID- 3352946 TI - [Evoked auditory potentials of medium latency in subjects with normal hearing]. AB - The parameters of normality in MLC to frequency-specific click and tone burst stimuli are analysed. Thirty four patients aged 15-50 with normal hearing revealed by preliminary subjective audiometry and impedance examination are examined for the following variables: threshold, latency, amplitude and repetitivity in response to click and tone burst stimuli. The audiometric and psychoacoustic thresholds were found to be closely connected. The MLC latency was in the 8-80 msec range as reported in the literature. Amplitude was neither significant nor reliable as a parameter since it varied so much from patient to patient, whereas the repeatability over time of these evoked potentials demonstrated their reliability. The results of this study confirm the view that MLC analysis is a valuable addition to the battery of diagnostic tests in routine use. PMID- 3352945 TI - [Determination of fibrinogen-fibrin degradation factors in neoplasms]. AB - Disseminated intravascular coagulation (DIC) and Primary Fibrinolysis (PF) are frequently reported in the literature as occurring in a wide variety of tumours whether subjected to chemotherapy or not and triggering a thrombohemorrhagic mechanism that is often fatal. It was therefore decided to assess the extent of the Fibrinogen-Fibrin Degradation Products (FDP) in a group of cancer patients in order to identify the primary, asymptomatic clinical expressions of these syndromes with a view to ascertaining the possibility of preventing more severe forms. The data confirm the presence of circulating FDP in a small percentage of the patients (26.9%) especially those with solid tumours metastasising to the liver. The involvement of that organ is therefore considered decisive for the onset of DIC and PF. PMID- 3352947 TI - [A case of AIDS-related complex (ARC/LAS) in a health worker]. AB - A case of ARC/LAS syndrome in a student nurse accidentally pricked by an infected needle is reported. This case-report is published to encourage the recognition of hospital staff. PMID- 3352948 TI - [Laryngospasm and hiatal hernia]. PMID- 3352950 TI - [X-ray computed tomography in latero-cervical lymph nodes, clinically undetectable, in preoperative staging of malignant neoplasms of the larynx]. AB - Postoperative CT of the latero-cervical lymph nodes was carried out in 25 patients suffering from laryngeal cancer. The surgically removed lymph nodes themselves were measured and examined histologically. 529/621 removed lymph nodes (about 85%) were recognisable with CT. The metastasized lymph nodes were clearly identified because of the presence of hypodense, poorly vascularised central foci. Some lymph nodes with a diameter of more than 15 mm on CT investigation proved free from metastatic lesions. This criterion should therefore be considered inadequate for diagnostic purposes. The CT cannot be held to be sufficiently precise to avoid conservative functional latero-cervical emptying as it is probably not able to recognise metastases without capsular rupture, not present in this series. PMID- 3352949 TI - [Pancreatic stone protein, a new marker for chronic pancreatitis]. AB - A CaCO3 precipitation and crystal growth inhibitor has recently been isolated from pancreatic calculi and from pancreatic juice. It is a glycoprotein with a molecular weight of 14,000, whose probable physiological role is the stabilization of exocrine pancreatic secretion which is normally supersaturated with CaCO3. It is hoped to determine a simple, but sensitive assay of this new protein on pancreatic juice and on serum, a decrease in which could be a marker for chronic pancreatitis. PMID- 3352951 TI - Partially overlapping territories of nerves to hindlimb foot skin demonstrated by plasma extravasation to antidromic C-fiber stimulation in the rat. AB - The innervation territories of the cutaneous nerves to the hindfoot were examined in the rat. Plasma extravasation of Evans blue to antidromic stimulation of C fibers in the saphenous, sural, peroneal and tibial nerves was the means to determine the innervation areas. A high degree of bilateral symmetry was found for the territory of each nerve in individual rats. Stimulation of pairs of nerves, one on each side, that innervate neighboring skin regions revealed the existence of overlapping territories for all pairs of nerves. The area of overlap was greatest on the toes and just proximal to the toes on the dorsum of the foot, whereas overlap on the volar aspect of the foot was minimal. The need to consider the existence of overlapping cutaneous innervation in normal animals in studies involving collateral sprouting after nerve injuries is discussed. PMID- 3352952 TI - Seasonal changes in inhibitory currents in rat hippocampus. AB - Spontaneous inhibitory postsynaptic currents were recorded in voltage-clamped neurons (clamp potential -60 to -70 mV) in the pyramidal cell layer of the CA1 region of hippocampal slices from 3- to 4-month-old rats. The average time constant of decay of the currents progressively increased from March (early autumn) to July (mid-winter) and then declined progressively from July to November (late spring). The changes were statistically significant. It is suggested that such seasonal changes in the time course of inhibitory postsynaptic currents may have behavioural consequences and could explain the reported seasonal variations in the occurrence of disorders such as mania. PMID- 3352953 TI - The protective effect of hypothermia on reversibility in the neuronal function of the hippocampal slice during long lasting anoxia. AB - The reversibility of neuronal function (postsynaptic potential and level of high energy phosphates) during deprivation of oxygen and/or glucose at 37, 28 and 21 degrees C was studied using hippocampal slices. The resistance of the neurons per se against anoxia could be well determined in the brain slice free from post anoxic circulatory disturbance. During deprivation of oxygen and glucose the survival time, the period of deprivation of oxygen and glucose during which neurons of the tissue slice can survive for recovery, was at 10, 15 and 45 min at 37, 28 and 21 degrees C, respectively. During deprivation of glucose only it was 1.5, 3 and 5 h at 37, 28 and 21 degrees C. During deprivation of oxygen only the survival time was 2.5, 5 and 15 h at 37, 28 and 21 degrees C. Deep hypothermia (21 degrees C) and the presence of glucose prolonged tremendously the survival time of the neurons of tissue slice during long-lasting anoxia. PMID- 3352955 TI - Long-latency baroreceptor inhibition of supraoptic neurones in the cat. AB - Experiments were done to determine the central delay to inhibition of supraoptic neurosecretory neurones by carotid baroreceptors in chloralose-anaesthetised, paralysed cats. Fourteen out of 18 neurosecretory cells (identified by antidromic activation from the pituitary neural lobe) were tested for their response to inflation of the ipsilateral carotid sinus (prepared as a blind sac). This stimulus inhibited the spontaneous activity of 10 neurones, which were thus identified as putative vasopressin cells. Repetitive, precisely timed pressure pulses were delivered to the carotid sinus and used to construct post-stimulus histograms of this inhibition. The latency measured from the baroreceptor afferent barrage (recorded from the sinus nerve) to the onset of inhibition in supraoptic neurones was 251 +/- 58 ms (range 152-328, n = 10). The significance of this long latency for the neural pathways involved is discussed. PMID- 3352954 TI - Changes in Ia reciprocal inhibition from the peroneal nerve to the soleus alpha motoneurons with different static body positions in man. AB - Experiments were conducted in man to evaluate the changes in Ia inhibitory interneurons activated from the anterior tibial muscle and projecting to the soleus alpha-motoneurons in relation to different static body positions. Subjects were fixed to a tilting chair and the effects of body rotation were evaluated at 80 degrees (normal sitting position) and 40 degrees of backward inclination (head supine, nose-up). A test H-reflex was used to assess changes in excitability of the soleus alpha-motoneurons after a conditioning stimulus applied to the deep peroneal nerve. In 5 out of 6 subjects, we observed a significant increase in the reciprocal inhibition after backward inclination of the body (40 degrees) with respect to the control position (80 degrees). Such increase was attributed to facilitation of the Ia inhibitory interneurons projecting to the soleus motoneurons. We consider the possibility that the observed increment in reciprocal inhibition after backward inclination be sustained by variations of tonic vestibular activity. PMID- 3352956 TI - Effects of intra-amygdalar dopamine agonists and antagonists on gastric stress lesions in rats. AB - Microinjections of dopamine (DA, 3 and 30 micrograms) or its agonist apomorphine (3 micrograms) into the central amygdala (CEA) attenuated cold restraint (3 h at 4 degrees C)-induced gastric ulcer formation in rats. Pretreatment with DA antagonists, haloperidol and metoclopramide (both i.p. and intra-amygdalar) reversed the stress ulcer attenuating effect of DA. It is suggested that the CEA is one of the central sites for this DA cytoprotection and that D2 receptors are possibly involved in this effect. PMID- 3352958 TI - Chronic in vivo ethanol administration alters the sensitivity of adenylate cyclase coupling in homogenates of rat brain. AB - The high activities of adenylate cyclase, phosphodiesterase and protein kinases in the synaptic terminals of the central nervous system makes these enzymes prime candidates for the in vivo actions of ethanol. Adult female rats were fed a liquid diet containing ethanol as 35% of the available calories for 6 days. This resulted in a decrease (22-45%) in the basal activity of adenylate cyclase, as determined by cyclic 3',5'-adenosine monophosphate (cAMP) production, in homogenates of all brain areas tested. In these homogenates the ability of guanosine triphosphate and noradrenaline to stimulate basal cyclase activity was severely reduced. These results suggest that ethanol administration causes an uncoupling of the beta-receptor/adenylate cyclase cascade and an interruption of the control of the synthesis of cAMP. PMID- 3352957 TI - Propentofylline (HWA 285) protects hippocampal neurons of Mongolian gerbils against ischemic damage in the presence of an adenosine antagonist. AB - The effect of the xanthine derivatives theophylline and propentofylline (HWA 285) on postischemic selective nerve cell damage was studied in the hippocampus of the Mongolian gerbil and assessed by measuring the decrease of Nissl staining in the CA1 area. Theophylline administered 15 min prior to a 2-min period of bilateral carotid occlusion led within 4 days to a marked damage of CA1 neurons which was not seen in untreated animals. Prolongation of the ischemic period to 5 min led to the same degree of damage in theophylline-treated and untreated animals revealing that the protective power of endogenous adenosine is limited. In contrast to theophylline, treatment with propentofylline (10 mg/kg, i.p.) antagonized cell death; such a protection by propentofylline was also achieved after 5 min ischemia in animals treated with theophylline. This indicates that propentofylline does not exert its protective effect via adenosine-mediated mechanisms. PMID- 3352959 TI - Age-dependent differences in cholinergic drug response in two strains of mice. AB - The behavioral effects of nicotine and oxotremorine were assessed in two strains of mice, C57BL/6 (C57) and DBA/2 (DBA), differing in the ontogeny of forebrain cholinergic structures. Both nicotine and oxotremorine depressed to a higher extent the behavior of DBA mice starting at day 45 of postnatal life. PMID- 3352960 TI - Determination of the pharmacokinetics of 2-amino-7-phosphonoheptanoate in rat plasma and cerebrospinal fluid. AB - The pharmacokinetics of 2-amino-7-phosphonoheptanoate (AP7) in rat plasma and appearance in cerebrospinal fluid (CSF) are reported. Using high-performance liquid chromatography (HPLC) with fluorescence detection, concentrations of AP7 can be detected as low as 1.0 microM. Peak CSF concentrations (12-15 microM) for both the D-AP7 and D,L-AP7 are observed 10-15 min after i.v. administration and amount to approximately 0.1% of a 1 mmol/kg dose. Significant quantities (3 microM) are present in CSF at 2 h and no AP7 is detectable at 4 h. Following i.v. administration, a monoexponential clearance was observed for D-AP7 clearance from plasma, 15.4 +/- 0.8 S.E.M. ml/min/kg with a t1/2 of 38.9 +/- 0.8 S.E.M. min. However, a biexponential clearance from plasma was observed for D,L-AP7. PMID- 3352962 TI - OBRA message is clear: quality or bust. PMID- 3352961 TI - Phosphorylation of elongation factor 2 in the rat superior cervical ganglion. AB - Elongation factor 2 (EF-2) and its associated kinase, Ca2+/calmodulin-dependent protein kinase III, have recently been identified as a major protein phosphorylation system in mammalian tissues. We have measured the phosphorylation of EF-2 in 32P-labeled superior cervical ganglia. Phosphorylation of EF-2 was increased by preganglionic stimulation or by treatment of the ganglion with dimethylphenylpiperazinium or veratridine. Increases in EF-2 phosphorylation presumably reflect the activation of Ca2+/calmodulin-dependent protein kinase III by nicotinic stimulation and depolarization. The phosphorylation of EF-2 may help to coordinate neuronal protein synthesis with neuronal activity. PMID- 3352963 TI - Teaching nurses the language of the marketplace. PMID- 3352965 TI - A valid profession needs valid diagnoses. PMID- 3352966 TI - In pursuit of accreditation. PMID- 3352964 TI - Budget-driven era demands new lesson plan. PMID- 3352968 TI - Always prepare an i.v. admixture before labeling the container. PMID- 3352967 TI - Child development center-nursing center partnership: a win-win arrangement. PMID- 3352970 TI - Know the early signs of HIV dementia complex. PMID- 3352971 TI - Princess of the city. PMID- 3352972 TI - How the easter bunny came to the I.C.U. PMID- 3352969 TI - Thank you, Barney. PMID- 3352973 TI - Electric window strangulation. PMID- 3352974 TI - Managing complications of i.v. therapy (continuing education credit). PMID- 3352976 TI - Try this new trauma assessment form. PMID- 3352975 TI - Do we discriminate against the elderly? PMID- 3352977 TI - Why you should teach your diabetic patients to chart. PMID- 3352978 TI - Cyanosis: the sign you can't count on. PMID- 3352979 TI - Get in touch and in tune with cardiac assessment. Part 1. PMID- 3352980 TI - Do you know all the legal answers? PMID- 3352981 TI - Mark's rehabilitation was a labor of love. Nursing grand rounds. PMID- 3352982 TI - A drug by any other name. Part 2. PMID- 3352984 TI - Test your knowledge of adult health care: gastrointestinal disorders. PMID- 3352983 TI - Welcome to our home. PMID- 3352986 TI - We hurt, too. PMID- 3352985 TI - Myths & facts about suctioning techniques. PMID- 3352988 TI - Pain control: too little, too late? PMID- 3352987 TI - How much do your patient know about AIDS? PMID- 3352989 TI - Kate kept her family together--until she fell apart. PMID- 3352990 TI - Get in touch and in tune with cardiac assessment. Part 2. PMID- 3352991 TI - When your patient needs spiritual comfort. PMID- 3352993 TI - Epiglottitis. PMID- 3352992 TI - More about charting with a jury in mind (continuing education credit). PMID- 3352994 TI - The battle against AIDS: a report from the nursing front. PMID- 3352995 TI - An almost-tragedy of errors. PMID- 3352997 TI - Giving drugs through an endotracheal tube. PMID- 3352998 TI - What's wrong with this patient? PMID- 3352999 TI - Think twice about borderline hypertension. PMID- 3353000 TI - The last game. PMID- 3353002 TI - Fever: different types, different causes. PMID- 3353001 TI - Beyond the wall. PMID- 3353003 TI - You're the jury. PMID- 3353004 TI - A legal perspective on the case. PMID- 3353005 TI - Mrs. Allen wouldn't change with the times. PMID- 3353006 TI - AIDS: the haunting facts, the human care (continuing education credit). PMID- 3353007 TI - The right to die. What nurses need to know. PMID- 3353008 TI - 10 legal safeguards for giving a deposition. PMID- 3353009 TI - Living with laws: How they differ from state to state. PMID- 3353010 TI - The missing expert witness. Is expert testimony needed to prove nursing negligence? PMID- 3353011 TI - [I, Helen, teaching clinical nurse....]. PMID- 3353012 TI - [Between approach and contents]. PMID- 3353013 TI - [The nurse and research]. PMID- 3353014 TI - [A shock for the heart. A new technic]. PMID- 3353015 TI - [Therese Rainville--honorary member of the A.Q.I.I.P. (Quebec Association of Psychiatric Nurses). Interview by Ghislaine Boucher]. PMID- 3353016 TI - [A nursing model in community health]. PMID- 3353017 TI - ["Health and therapies...", colloquium of international scope]. PMID- 3353018 TI - [Four years with the Accreditation Committee]. PMID- 3353019 TI - [Personalized nursing care: a deontologic question]. PMID- 3353021 TI - [Position statement. Care complementary tools]. PMID- 3353020 TI - [World health--an international dimension]. PMID- 3353022 TI - Antecedents from adjunctive disciplines: creation of nursing theory. PMID- 3353023 TI - Concepts: essential elements of theories. PMID- 3353024 TI - Wallowing while waiting. PMID- 3353025 TI - Structuring nursing knowledge: a priority for creating nursing's future. PMID- 3353026 TI - Research blenders. PMID- 3353027 TI - Theory-based practice: structuring nursing care. PMID- 3353028 TI - The art and science of nursing: similarities, differences, and relations. PMID- 3353029 TI - Medical and health library resources in New Zealand. PMID- 3353030 TI - Impact of private medical insurance on the demand for child consultations with general practitioners. AB - Data were collected on over 4000 consultations with general practitioners for childhood complaints. Almost half of these consultations (46%) were covered by private medical insurance. A larger proportion of consultations for respiratory conditions were covered by insurance (50%) compared to those for nonrespiratory conditions (42% insured). Amongst those with respiratory conditions larger proportions of consultations for upper respiratory tract infections were insured (50%) than was the case for the potentially more serious conditions of asthma or otitis media (46% insured). The delay in seeking consultation for respiratory conditions was examined. In consultations for followup or persisting problems there was less delay among the insured (8.7 days) than amongst the noninsured (11 days). Those consultations initiated by the patient (or parent) were more likely to be covered by insurance (50%) than those which had been initiated by the doctor or other agency (44%). The findings are discussed in terms of the implications for equity and efficiency in health care. PMID- 3353031 TI - Campylobacter pylori infection in patients undergoing endoscopy in Fiji. AB - Forty two patients (20 Fijian and 22 Indian) presenting for endoscopy at the Colonial War Memorial Hospital, Suva, Fiji, were biopsied to detect Campylobacter pylori infection. Detection of the organism's urease activity in biopsy material or seeing the organism in Warthin-Starry silver stained histology sections were used to diagnose infection. Thirty-nine patients (93%) were infected; 19 of 20 Fijians (95%) and 20 of 22 Indians (91%). Of the 39 infected patients, 37 (95%) had chronic active gastritis and 24 (62%) had active peptic ulcer disease. The implications of these findings in relation to the management of endoscopy patients in Fiji are discussed. PMID- 3353033 TI - Electronic communication with colleagues overseas. PMID- 3353034 TI - Chelation therapy. PMID- 3353032 TI - High school students' attitudes towards and use of contraceptives. AB - A questionnaire survey was conducted in an urban coeducational secondary school in the North Island region. Of the 162 adolescents sampled in this study, 39 percent reported coital experience. Of these coitally experienced students, contraception was always used by only 42%. The pill and the condom were reported as the most used contraceptives. Females were found to be significantly better contraceptive users than males. Although many students report preferring their parents as a source of contraceptive information, the majority of both males and females relied upon school sex education classes as their main source of their contraceptive education. Students ability to discuss contraceptive matters with parents was found to have no effect upon coital activity. These results indicate that society must come to terms with the fact that many adolescent New Zealanders are sexually active and run a high risk of having unplanned, unwanted pregnancies. PMID- 3353035 TI - State control versus private enterprise. PMID- 3353037 TI - Urine microscopy and culture. PMID- 3353036 TI - The personal view from a deputising service. PMID- 3353038 TI - Toilet training in children. PMID- 3353041 TI - Why is it difficult to obtain prednisolone in New Zealand? PMID- 3353040 TI - High risk groups for chlamydial infection. PMID- 3353042 TI - Fetal foot length: relationship to menstrual age and fetal measurements in the second trimester. AB - The purpose of this study was to describe the ultrasonic measurement of fetal foot length and to develop mathematical models to quantify the relationships between menstrual age and commonly measured fetal structures. We evaluated 120 patients with known last menstrual periods and normal pregnancies to develop a cross-sectional study population. All patients had ultrasonic measurement of the fetal foot length, biparietal diameter, head circumference, abdominal circumference, and femur length. Least-squares estimation of linear models was used to select the best mathematical models to describe the relationship between menstrual age and fetal foot length. A similar evaluation of the relationship between fetal foot length and the other measured parameters was performed. All models were best described by a linear equation. An R2 value of 0.94, with a standard error of the estimate of 0.204, was obtained for menstrual age versus fetal foot length. When the model for fetal foot length and menstrual age was compared with published anatomical data, close agreement was seen over the time interval studied. Our results suggest that the measurement of fetal foot length with ultrasound gives a reliable assessment of anatomical fetal or neonatal foot length and is highly correlated to the menstrual age of the fetus. PMID- 3353039 TI - Human dwarf tapeworm Hymenolepsis nana in rats in Western Samoa. PMID- 3353043 TI - Determinants of fetal heart rate response to vibroacoustic stimulation in labor. AB - To determine whether the fetal heart accelerates in response to a sound stimulus in labor, 40 women at various stages of labor were chosen at random to receive either a vibroacoustic stimulus or sham stimulus over the fetal head. Subsequent fetal heart rate (FHR) accelerations occurred to a significantly greater extent in study patients. One hundred thirty-two high- and low-risk patients were studied to determine correlations between the acceleration response and other maternal and fetal variables. There was a statistically significant negative correlation between the heart rate response to stimulation and three maternal variables: the degree of cervical dilation, the presence of ruptured membranes, and use of epidural anesthesia. The degree of fetal response did not correlate significantly with fetal distress at delivery or abnormal FHR tracings at the time of stimulation. Fewer than one-fifth of the fetuses manifested variable heart rate decelerations after the stimulation. In light of possible risks, the clinical use of the fetal acoustic stimulation test in labor should wait until its diagnostic value is better defined. PMID- 3353044 TI - Labor pain: a comparison of parturients in a Dutch and an American teaching hospital. AB - Women giving birth in two university hospitals, one in the Netherlands and the other in the United States, were surveyed postpartum regarding expectations of pain in labor and availability of medication for its relief, perceptions of the painfulness of labor, and use of analgesia and anesthesia. American women expected labor to be more painful, anticipated that they would receive medication for it, and did receive such medication in significantly greater proportions compared with Dutch parturients. These findings point to fundamental, culturally determined differences between these two societies with respect to women's views of the painfulness of childbirth. PMID- 3353045 TI - Cervical cerclage for the temporary treatment of patients with placenta previa. AB - Cervical cerclage as a temporizing measure for the treatment of patients with placenta previa was evaluated in 25 patients admitted to the hospital for vaginal bleeding between 24-30 weeks' gestation and sonographic evidence of a placenta previa. The patients were randomly assigned to either cerclage (13) or conventional management (12). Cerclage patients had significantly better perinatal outcome, as indicated by more advanced gestational age at the time of delivery (34.9 +/- 3.0 versus 31.6 +/- 2.9 weeks; P = .02), larger birth weight (2709 +/- 511 versus 1812 +/- 506 g; P = .002), and fewer neonatal complications (two of 13 versus ten of 12 infants; P = .001). Maternal bleeding was more frequent and severe for patients in the control group. The total hospital cost was less for cerclage patients than for those receiving conventional expectant management ($9898 +/- 3943 versus $27,271 +/- 9901; P = .02). These results support the use of cervical cerclage for the treatment of patients with symptomatic placenta previa early in gestation. PMID- 3353046 TI - The natural history of preterm ruptured membranes: what to expect of expectant management. AB - We asked the question: What can be expected of expectant management in preterm ruptured membranes? Our findings showed that ruptured membranes during the first half of the third trimester occurred in only 1.7% (N = 298) of 17,877 pregnancies delivered at our institution, yet accounted for 20% of the total perinatal deaths during the study period. Expectant management was seldom successful; only 20 (7%) of pregnancies with preterm ruptured membranes did not begin labor within 48 hours. The condition of preterm ruptured membranes was also frequently associated with other obstetric complications such as twins, breech presentation, chorioamnionitis, and fetal heart rate decelerations in labor. We conclude that preterm ruptured membranes is an uncommon but complex obstetric problem that remains largely unsolved. PMID- 3353047 TI - Connective tissue changes in the cervix during normal pregnancy and pregnancy complicated by cervical incompetence. AB - When postpartum cervical biopsy specimens were compared with biopsy specimens from nonpregnant women, they revealed a 12-fold decrease in mechanical strength, a 50% reduction in the concentrations of collagen and sulfated glycosaminoglycans, a 35% reduction in hyaluronic acid, an increase in collagen extractability, and a fivefold increase in collagenolytic activity. Primiparas with relatively high concentrations of collagen and hyaluronic acid had relatively long cervical dilatation times during established labor, suggesting a physiologic importance to these variables. This correlation was not found in multiparas, even though the mean values of the biochemical parameters tested were similar to those in primiparas. Second-trimester biopsy specimens taken from patients with cervical incompetence contained normal collagen concentrations, but relatively high collagen extractabilities and collagenolytic activities, exceeding normal postpartum values. A biopsy specimen that was tested biomechanically had a very low strength and very high extensibility. Most likely, these data reflect a high turnover of collagen in incompetent cervices, resulting in a high proportion of newly synthesized collagen with low biomechanical strength. PMID- 3353048 TI - Determination of the elastic properties of the cervix. AB - The elastance of the uterine cervix of nonpregnant women was measured by placing a 3- or 4-cm compliant balloon in the cervical canal and determining its pressure volume characteristic while filling with up to 5 mL of sterile water at a rate of 12 mL/minute. The mean elastance for 247 patients who had previously suffered either one or more spontaneous midterm pregnancy losses, preterm birth, or three or more early spontaneous abortions was significantly lower than that of 42 controls who did not meet these criteria. Elastances were significantly lower in groups having a clinically observed patulous cervix or laceration, or a clinically diagnosed incompetent cervix, than in the normal cervix group. No significant difference was found between the follicular and luteal phases for 64 regularly cycling women. Values were significantly reduced in women showing a widened cervix on a hysterosalpingogram when compared with those with a normal appearing cervix. When larger Hegar dilators were passed without resistance, the elastance was generally lower, although there was not always good correlation between the largest dilator passed and elastance. PMID- 3353049 TI - Surgical treatment of stress urinary incontinence: a comparison of the Kelly plication, Marshall-Marchetti-Krantz, and Pereyra procedures. AB - Six hundred eighty patients surgically treated for stress urinary incontinence were observed annually for up to ten years to compare the efficacy and complications of three types of repair procedures. Although Marshall-Marchetti Krantz procedures yielded the most effective repair in the immediate postoperative period, Kelly plications were equally corrective more than three years after surgery (69 and 66%, respectively). Both were superior to the original Pereyra urethropexies at all times. Repeat operations were more likely to fail than primary repairs. The efficacy of the Pereyra procedure was increased with the use of permanent suture. Marshall-Marchetti-Krantz procedures were not affected by suture selection. Pereyra procedures had more complications, many related to intravesical suture. Success rates of all procedures declined steadily with lengthening periods of observation. We conclude that Kelly plications and Marshall-Marchetti-Krantz procedures have similar long-term efficacy and complication rates. The use of intra-operative cystoscopy and permanent suture with the Pereyra procedure might make it competitive. PMID- 3353050 TI - Oral contraceptives and the hemostatic system. AB - We studied 30 control women and 131 pill users to evaluate effects of birth control pills and clinical factors on hemostasis. When control patients were matched with an equal number of pill users, none of the direct markers of activated hemostasis (fibrinopeptide A, platelet factor 4, and beta thromboglobulin) were increased. Plasminogen, prekallikrein, and protein C (protective against clotting) were significantly higher in pill users. Fibrinogen, antithrombin, alpha-2 antiplasmin, and fibronectin were comparable. Among the 131 pill users, antithrombin levels decreased with a family history of thromboembolism. Fibrinogen and fibronectin were increased with obesity, but there was no evidence of activated hemostasis. Overall, pill use did not appear to result in hypercoagulability. Considering family history of thromboembolism might further improve the safety of oral contraceptive use. PMID- 3353052 TI - Proline aminopeptidase activity as a rapid diagnostic test to confirm bacterial vaginosis. AB - Two biochemical indicators of bacterial vaginosis, proline aminopeptidase activity and gas-liquid chromatographic analysis, were compared. Five hundred women had their vaginal secretions tested for pH, presence of a positive amine test, levels of volatile and nonvolatile short-chain organic acids, and proline aminopeptidase activity. In addition, direct microscopic and Gram stain examinations were performed. Of the 500 women, 349 (70%) had some form of vaginitis. One hundred sixteen were diagnosed as having bacterial vaginosis, and 69 of these (59%) had Mobiluncus sp on either direct microscopic or Gram stain examination. Two hundred thirty-three had either mixed or other forms of vaginitis. One hundred fifty-one patients were normal. The sensitivity of the proline aminopeptidase assay was 83 and 79%, respectively, in patients having bacterial vaginosis with and without Mobiluncus morphotypes. In contrast, gas liquid chromatography of short-chain organic acids had sensitivities of 71 and 30%, respectively. Specificity of both assays was about 95%. The greater sensitivity of the proline aminopeptidase assay, especially in patients without Mobiluncus morphotypes, proves its superiority. PMID- 3353051 TI - Outpatient treatment of pelvic inflammatory disease with cefoxitin and doxycycline. AB - Sixty-three women with abdominal pain and adnexal tenderness were enrolled in a study of ambulatory treatment of acute pelvic inflammatory disease. Treatment consisted of 2 g of cefoxitin intramuscularly and 1 g of probenecid orally, followed by doxycycline, 100 mg by mouth twice daily for 14 days. Patients were stratified into groups indicating whether pelvic inflammatory disease was probable, possible, or unlikely, based upon endometrial biopsy and clinical criteria. Among 52 women who were evaluated, Chlamydia trachomatis and/or Neisseria gonorrhoeae were initially recovered from 16 (67%) of 24 with probable pelvic inflammatory disease, three (33%) of 11 with possible pelvic inflammatory disease, and three (18%) of 17 in whom pelvic inflammatory disease was considered unlikely. Of the 24 patients with probable pelvic inflammatory disease, 22 (92%) were clinically cured or improved. Of 22 patients initially infected with C trachomatis and/or N gonorrhoeae, 20 were culture-negative for both organisms after therapy. Both microbiologic failures had been reexposed. This study suggests that the combination of cefoxitin and doxycycline is effective for ambulatory treatment of pelvic inflammatory disease. PMID- 3353053 TI - Accuracy of office and operating room curettage in the grading of endometrial carcinoma. AB - This retrospective study reviewed the records of 375 patients with clinical stage I adenocarcinoma of the endometrium. After criteria for exclusion were applied, 223 patients were analyzed further. Results from office and operating room curettage were compared with findings at hysterectomy. Twenty percent of cases showed an increase in grade at hysterectomy after office curettage; 15% showed upgrading after operating room curettage, a nonsignificant difference. We conclude that the techniques have equivalent accuracy in the determination of tumor grade. However, despite their well-documented reliability in tumor detection, a 15-20% upgrade suggests that frozen section confirmation of grade and depth of invasion in the hysterectomy specimen may be necessary if further surgical staging is not already planned. PMID- 3353054 TI - Southeast Asian folklore about pregnancy and parturition. AB - Southeast Asian refugees immigrating to the United States bring many traditional beliefs about pregnancy and childbearing to their new home. Harmony with nature, dualistic concepts of disease, and pathogenetic metaphor are important ingredients of indigenous health practices. Pregnant and postpartum women must be protected against "wind," lost of "heat," and poisons. Because these notions and the behaviors used to carry them out may seem bizarre to unsuspecting Western trained health care personnel, it is important for Westerners to understand the basis for these beliefs. PMID- 3353055 TI - Funipuncture: a rose by any other name.... PMID- 3353056 TI - A suburethral sling procedure with polytetrafluoroethylene for the treatment of genuine stress incontinence in patients with low urethral closure pressure. AB - One indication for suburethral sling procedures has been recurrent genuine stress incontinence after previous incontinence surgery. Patients with low urethral closure pressures (20 cm H2O or less) in association with genuine stress incontinence are at particular risk for failure of standard anti-incontinence procedures. Urodynamic evaluation was used to select 17 patients with genuine stress incontinence and low urethral closure pressures for surgical treatment with a sling procedure using polytetrafluoroethylene. The technique of the procedure, cure rate, and postoperative complications were assessed. An 85% subjective and objective cure rate was found on urodynamic testing three months postoperatively. Complications included wound seroma, urinary tract infection, and urinary retention. PMID- 3353057 TI - A semiquantitative human chorionic gonadotropin assay for the detection of ectopic pregnancy. AB - Human chorionic gonadotropin (hCG) was measured in 117 serum samples with known quantities of hCG after a dilutional modification of a reliable, simple, and inexpensive qualitative assay for hCG. The modification yielded a semiquantitative assay for hCG with a sensitivity of 5000 mIU/mL. At hCG concentrations below 4000 mIU/mL, the assay had no false-negative or false positive results; above 6500 mIU/mL, there were also no false-negative or false positive results. In the range of 4000-6500 mIU/mL, the clinical false-positive rate was 28%. Using the described dilutional modification of this qualitative hCG assay, the test is semiquantitative, and is useful in selecting the appropriate time to perform ultrasound and laparoscopy in women suspected of having an ectopic pregnancy. PMID- 3353058 TI - An active management approach to the postdate fetus with a reactive nonstress test and fetal heart rate decelerations. PMID- 3353059 TI - COSHH and carcinogens. PMID- 3353060 TI - Cancer education at the workplace. PMID- 3353061 TI - A look at skin cancer. PMID- 3353062 TI - OH on the fireground. PMID- 3353063 TI - Getting it right on the beautiful Moray Firth. Interview by Jane Wilson. PMID- 3353064 TI - Disclosure of records. PMID- 3353065 TI - "Beware the Ides of March". PMID- 3353066 TI - AIDS testing. PMID- 3353067 TI - AIDS surveillance update: Ohio 1987. PMID- 3353068 TI - Ohio to get three AIDS research centers. PMID- 3353069 TI - Getting professional help. Hiring a marketing firm. By the OSMA Department of Communications and Physician Marketing. PMID- 3353070 TI - PICO: 1987 in review. PMID- 3353071 TI - Help for the adolescent health crisis. PMID- 3353072 TI - Association of skin and other lesions with cervical dysplasia. AB - Association is reported in a series of 805 patients between cervical dysplasia and the occurrence of lesions in other organs, in particular the skin. The occurrence of associated lesions in these patients was markedly in excess of that in case-matched controls. It was not related to the increased frequency of gynaecological investigation in patients with cervical dysplasia. Pigmented naevi were the most common associated lesions, occurring before and after the diagnosis of cervical dysplasia. Three cases of malignant melanoma were seen in the test group. Gynaecological lesions were also common. The findings are discussed in the light of recent work on viral synergism in genital neoplasia. PMID- 3353073 TI - Adjuvant chemotherapy for murine neuroblastoma with special reference to cell kinetics of residual tumor after primary tumor removal. AB - We examined the effect of adjuvant chemotherapy for neuroblastoma (C-1300NB) after surgery, especially on the increase in cells in the DNA synthetic phase in the remaining neuroblastoma from the 6th to 24th postoperative h caused by the reduction of the tumor cell in the tumor-bearing A/J mice. The mice were inoculated with C-1300NB cells in the chest and leg simultaneously, and administered adriamycin (ADM), as a cell cycle phase-specific agent, or cyclophosphamide (CPM), as a cell cycle phase nonspecific agent. The growth rate of chest tumors (residual tumors) in the mice treated with ADM just after amputation of the tumor-bearing leg was significantly lower than that of the other groups (p less than 0.05). 3H-TdR labeling indices of chest tumors in this group decreased more effectively than in the other groups. These results indicate that it is important to administer a cell cycle phase-specific agent rather than a cell cycle phase nonspecific agent during the period of rapid growth of residual tumors after surgery. PMID- 3353074 TI - Inhibition of 12-O-tetradecanoylphorbol-13-acetate-stimulated 32Pi incorporation into phospholipids and protein phosphorylation by 2,7,11-cembratriene-4,6-diol, an antitumor-promoting agent. AB - A possible mechanism of antitumor-promoting activity of alpha-2,7,11-cembratriene 4,6-diol (alpha-CBT) was studied. alpha-CBT inhibited the 32Pi incorporation into phospholipids of HeLa cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast to the property to interact with calmodulin of many other antitumor-promoting agents, which were proved to inhibit TPA-stimulated 32Pi incorporation into phospholipids, alpha-CBT did not show any interaction with calmodulin; i.e., the fluorescence of N-phenyl-1-naphthylamine enhanced by binding with Ca2+-calmodulin was not influenced by treatment with alpha-CBT. TPA stimulated phosphorylation of 47-kilodalton protein, which is phosphorylated by protein kinase C in human platelets, was found to be inhibited by alpha-CBT. However, the specific binding of 3H-TPA to mouse epidermal particulate fraction was not inhibited by treatment with alpha-CBT. These results suggest that alpha CBT inhibits the activity of protein kinase C by another mode of action rather than the effect on its receptor site, and that this action and calmodulin independent inhibitory effect on phospholipid metabolism of alpha-CBT may play a certain role in its antitumor-promoting activity in vivo. PMID- 3353075 TI - Regional pharmacokinetic selectivity of intraperitoneal cisplatin in ovarian cancer. AB - Five patients with intraabdominal ovarian cancer, 4 of whom with concomitant ascites, refractory to cisplatin-containing combination chemotherapy were treated with intraperitoneal cisplatin. Cisplatin, 90 mg/m2, was administered intraperitoneally in 2 liters of warm 0.9% NaCl with a 4-hour dwelling time on day 1 q 21 days. Platinum concentrations in plasma, ascites, ultrafiltrates of plasma and ascites, and urine were assayed by flameless atomic absorption spectrophotometry and determinations were verified by neutron activation analysis. Peak total and ultrafiltrable plasma platinum levels were 1.63 +/- 0.6 and 0.76 +/- 0.3 microgram/ml, respectively. Peritoneal clearance of total platinum (PA) was 21 ml/min whereas body clearance of total platinum was on the average 13.8 times PA, varying from 171 to 429 ml/min; the mean AUC (peritoneum) to AUC (plasma) ratio was 11 +/- 3. In 2 patients control of ascites was obtained, in 1 of these patients prior positive cytology became negative after her first intraperitoneal course. No nephrotoxicity was observed and gastrointestinal toxicity was mild. No catheter-related infections were observed. Intraperitoneal cisplatin therapy is well tolerated, pharmacokinetically rational and may be useful in managing ovarian cancer patients with malignant ascites or minimal residual disease at second-look laparotomy. PMID- 3353076 TI - High doses of methylprednisolone with or without alizapride in the prevention of cisplatin-induced emesis. A randomized, double-blind, crossover study. AB - Fifty-two patients undergoing cisplatin-based chemotherapy were randomized to receive either methylprednisolone (1 g i.v. total dose) or methylprednisolone plus alizapride (800 mg i.v. total dose). Major control of emesis (less than or equal to 2 episodes of vomiting) was obtained in around 30% of patients, without difference between the two arms. The combined antiemetic treatment was significantly superior to the single drug in reducing overall number of vomiting episodes (median: 4 vs. 9), duration of emesis (2 vs. 4.5 h), and number of patients with more than 5 vomiting episodes (47.5 vs. 62.5%). Both antiemetic regimens had negligible toxicity and were easily given to outpatients. Though some superiority has been shown for the combined treatment over the single methylprednisolone, the low rate of major control of emesis does not warrant for further investigations of this regimen in cisplatin-treatment patients. PMID- 3353077 TI - Multiple myeloma presenting with spinal cord compression. AB - The clinical features, treatment, and course of 6 patients with multiple myeloma, who presented initially with spinal cord compression, are reviewed. These 6 represent 12% of all patients with myeloma seen at our institution since 1979. Eighty-three similar patients were identified from the medical literature. There are no patient characteristics predictive for this presentation. A higher than expected proportion of patents have clinically localized disease, but progression to myelomatosis is common. As these patients present without a known diagnosis of malignancy, a prompt, invasive diagnostic procedure and the immediate institution of definitive local therapy is mandatory. Despite such an aggressive approach, the prospect for significant return of neurologic function is poor. Survival does not appear to be different from that of other patients with myeloma. Unlike other malignancies, a presentation with cord compression is not inconsistent with long term survival, although significant morbidity secondary to the resultant functional disability can be expected. PMID- 3353078 TI - Decline of childhood cancer mortality in Italy, 1955-1980. AB - The decline in childhood cancer mortality in Italy from 1955 to 1980 has been evaluated through (1) comparison of age-specific and age-standardized (0-14 years) rates for the periods 1955-1960 and 1979-1980 and (2) computation of expected numbers of deaths by application of the age-specific rates for the period 1955-1960 to the population structure of subsequent periods. Certified mortality fell by 35% for leukaemias, 90% for Hodgkin's disease, 30% for non Hodgkin's lymphomas, 40% for bone sarcomas, 30% for kidney (Wilms') tumours, 65% for retinoblastoma. No clear trend was reported for other neoplasms, including neuroblastoma. About 300 cancer deaths per year were avoided in the period 1979 1980 compared with the expected number based on the 1955-1960 rates (170 for leukaemias alone). Although clearly encouraging, these trends are substantially less favourable than those from several other developed countries. It is therefore likely that several dozen other deaths from childhood cancer could be avoided each year through earlier (or more accurate) application of effective therapies, particularly for neoplasms requiring radiotherapy or surgical treatment. PMID- 3353079 TI - The value of a monoclonal anti-epithelial antibody (mAB lu-5) in the differential diagnosis of tumors. Immunohistochemical study. AB - The usefulness of a monoclonal anti-epithelial antibody, mAB lu-5, was assessed in the histologic differential diagnosis of 102 formalin-fixed, paraffin-embedded tumors including various carcinomas, sarcomas and lymphomas. A variety of nontumorous tissues were also evaluated. Although mAB lu-5 failed to provide conclusive results in a few cases, in general, it was found to be a reliable immunohistochemical marker of tumorous and nontumorous epithelial cells. Immunostaining with mAB lu-5 did not distinguish between tumorous and nontumorous tissues and between benign and malignant tumors. Further work is required to clarify the significance of strong immunoreactivity noted in chorionic epithelium and pituitary corticotrophs. PMID- 3353080 TI - Responsibilities in animal experimentation. PMID- 3353081 TI - Corneal rupture following radial keratotomy in cats subjected to BB gun injury. AB - We performed this investigation to determine if radial keratotomy (RK) predisposes an eye to rupture when exposed to projectile trauma. Radial keratotomy was performed on 22 cat eyes; 17 eyes were used as controls. Incision depth was set at 90% by averaging ten corneal thickness readings by ultrasonic pachymetry of each cornea. An optical zone of 4.0 mm was used and eight incisions were made. Eight weeks after RK the cats were divided into three groups, subjected respectively to BB velocities of 148.5 ft/sec (N = 4), 190 ft/sec (N = 5), and 240 ft/sec (N = 13). In groups 1 and 2, all nine eyes had hyphemas and no eyes perforated. In group 3, four of 13 RK eyes had corneal rupture. All control eyes had hyphemas and none ruptured. The study suggests that RK can predispose to rupture eyes exposed to projectile trauma sufficient to produce hyphema. PMID- 3353082 TI - Transpupillary argon laser cyclophotocoagulation in the treatment of glaucoma. AB - Twenty-seven patients with glaucoma, which could not be controlled with maximum tolerable medication and standard laser techniques, underwent transpupillary argon laser cyclophotocoagulation. Only six patients (22.3%) had a successful outcome, and the postoperative course in many cases was complicated by an additional, sustained increase in intraocular pressure. Notwithstanding these results, the procedure may be useful occasionally to preclude the need for conventional glaucoma surgery. PMID- 3353083 TI - Choroiditis compatible with the histopathologic diagnosis of sympathetic ophthalmia following cyclocryotherapy of neovascular glaucoma. AB - A 44-year-old man had a blind painful right eye secondary to neovascular glaucoma. Cyclocryotherapy was performed because medical therapy was ineffective in lowering the intraocular pressure or reducing the pain. The eye became comfortable, but 5 months later vision decreased in the left eye. Examination revealed a marked posterior uveitis suggestive of sympathetic ophthalmia. Enucleation of the right eye and corticosteroid therapy were effective in eliminating inflammation in the left eye. Histopathologic examination of the exciting right eye revealed classic signs of sympathetic ophthalmia. This case is particularly unusual because there was no history or evidence of ocular perforation in the exciting eye. PMID- 3353084 TI - The PAR IS 2000: a new system for retinal digital image analysis. AB - We describe the PAR IS 2000, a new system of digital image analysis of the optic disc. The system uses a simultaneous stereoscopic camera and a video camera to acquire images directly from the optic disc and from optic disc photographs, respectively. The image data are stored on an optical laser disk capable of handling large amounts of data (4000 monochrome images/disk). These images can be analyzed using a modified digital interactive mapping program to generate stereometric parameters, contour maps, section profiles, pallor maps, depth maps, and three-dimensional topographic plots of the retina. A skeletonizing program permits determination and measurement of shifts in the position of retinal vessels. The system's wide range of capabilities may be helpful in improving patient care and ophthalmic research. PMID- 3353085 TI - A surgical technique for the successful and stable reconstruction of the totally contracted ocular socket. AB - We describe the successful and stable reconstruction of 47 severely contracted sockets over a 10-year period. The surgical technique employed in all these cases used a large custom-designed, C-shaped conformer wrapped with a full-thickness oral mucous membrane graft. After all cicatricial tissue within the socket was excised, the wrapped conformer was sutured at its midperiphery to the inferior and superior orbital rims. In contrast to other procedures using flatter conformers, which direct their force in a vertical dimension, this uniquely designed conformer directs its force both vertically and deeply posteriorly within the socket. A somewhat modified but similar conformer also can be used for sockets compromised by total symblepharon formation. Excluding six patients with inadequate follow-up, we were able to successfully reform spacious and stable fornices in 40 of 41 severely contracted sockets. The average postoperative follow-up after reconstruction in these cases was 23.9 months. This technique represents an effective approach to successfully reconstruct and maintain stable ocular cul-de-sacs in cases of severe socket contracture or total symblepharon formation. PMID- 3353087 TI - A method of monocanalicular silicone intubation. AB - A method for silicone intubation of a single canaliculus is described. A lacrimal stent has been crafted from a short segment of silicone tubing and a punctal plug. The distal end of the stent is fixed in the punctum with a punctal plug. The silicone stent, which is attached to the punctal plug, bridges the canalicular laceration. Because the punctal plug remains fixed in the punctum, no sutures are needed to fixate the stent to the eyelid. PMID- 3353086 TI - CT scan of cutaneous lacrimal (anlage) fistula. AB - We report CT visualization of both a rare congenital lacrimal fistula and a large mucocele of the lacrimal sac on the opposite side of the same patient. CT scan visualization of a patent anlage fistula has not been reported previously. CT scans can demonstrate extensive orbital abnormalities not detectable by routine clinical or radiologic evaluation. PMID- 3353088 TI - A simplified scleral graft technique for covering an exposed orbital implant. AB - A simplified method of covering an exposed orbital implant is presented. Donor sclera is placed between Tenon's capsule and the spherical implant without dissecting any tissue planes between the conjunctiva and Tenon's capsule. Technical manipulations and bleeding are thereby minimized. Preplaced absorbable sutures in the periphery of the graft are externalized and tied to the anterior surface of the conjunctiva. PMID- 3353090 TI - Anticoagulants and cataract surgery. AB - A series of 49 cataract operations in 42 patients is presented in support of our contention that if anticoagulants are necessary for a patient's well being, they should not be discontinued for cataract surgery. PMID- 3353089 TI - Prediction of post cataract extraction visual acuity: 10 Hz visually evoked potentials. AB - Cataract patients suspected of having disease that might interfere with good postoperative visual function were evaluated by eliciting monocular steady-state luminance visual evoked potentials (VEPs) with closed eyes at a stimulus rate of 10 flashes/sec. VEPs were rated as either normal or abnormal. Patients with normal VEPs were predicted to have visual acuity of 6/15 (20/50) or better. Patients with abnormal VEPs were predicted to have acuities of 6/18 (20/60) or worse. Postoperative acuities were determined for all patients who underwent surgery and who had no intraoperative or early postoperative complications. The predicted and observed postoperative acuities were quantitatively compared for the 59 patients who met these criteria, using a 2 X 2 contingency table. The chi square was significant (p less than .001). The overall accuracy of prediction was 80%. Accuracy of the predictions for patients with preoperative acuities of 6/60 (20/200) or better was compared with the accuracy of the predictions for those with preoperative acuities of 60/120 (20/400) or worse. There was no significant difference (p greater than 0.10). PMID- 3353091 TI - Clockwise versus counterclockwise rotation. PMID- 3353092 TI - The effect of carbachol combined with intraoperative viscoelastic substances on postoperative IOP response. PMID- 3353093 TI - The developmental success of Amblyomma hebraeum and Amblyomma marmoreum on the leopard tortoise, Geochelone pardalis. AB - The success of natural infestations of various life history stages of Amblyomma hebraeum and Amblyomma marmoreum on the leopard tortoise, Geochelone pardalis, was compared. Success was measured by the time taken for ticks to detach, as well as the percentage of ticks engorging and subsequently either moulting to the next life history stage or laying viable eggs. Larvae of A. hebraeum were the only developmental stage not recovered. Nymphae and female A. hebraeum were less successful in moulting or laying eggs than the corresponding stages of A. marmoreum. Nevertheless, 48,7% of A. hebraeum nymphae moulted, while 1 of 6 females laid viable eggs. PMID- 3353094 TI - The characteristics of a variant strain of Brucella melitensis Rev 1. AB - Circumstantial evidence is presented for the occurrence of a variant of a vaccine strain of B. melitensis Rev 1, designated "FSA" (foreign South African). FSA resembles Rev 1 in its reactions to penicillin and streptomycin but reacts closer to a field strain of B. melitensis as regards dye (thionine and basic fuchsin) sensitivity and colony size. Although colonies of Rev 1 were consistently smaller than other B. melitensis strains, their size was 0,75 mm as opposed to the 1-2 mm reported in the literature, while B. melitensis 16M colonies were 1,25-1,5 mm as opposed to the 3-4 mm previously reported. Rev 1 was found to be urease positive, unless a test of low sensitivity was applied. PMID- 3353096 TI - Ascites and the anatomy of the peritoneal sacs of broilers. AB - Although the ascites syndrome of broilers is well documented, all the authors fail to describe exactly in which of the various coelomic cavities ascitic fluid is found. Determination of the precise location of this fluid is essential if the pathogenesis of the syndrome is to be understood and explained. Post-mortem examinations were done on 100 broilers that had ascites or had died of the ascites syndrome. In all of them large quantities of fluid were found in the ventral hepatic peritoneal cavities, moderate amounts in the right dorsal hepatic peritoneal cavities and small amounts in the intestinal peritoneal and pericardial cavities. No ascitic fluid was found in the left dorsal hepatic peritoneal cavity. The amount of ascitic fluid effusing from the liver was directly proportional to the surface area of the liver in a given peritoneal cavity. PMID- 3353095 TI - Arthropod parasites of common reedbuck, Redunca arundinum, in Natal. AB - Twenty-five common reedbuck, Redunca arundinum, from the Himeville region, 21 from the Eastern Shores Nature Reserve, 4 from the Charter's Creek Nature Reserve and 2 from the St Lucia Game Park, Natal were examined for arthropod parasites. The reedbuck from Himeville were infested with 4 ixodid tick species, those from the Eastern Shores with 7 species and those from Charter's Creek and St Lucia with 6 species. Rhipicephalus evertsi evertsi was the only tick common to the 4 localities. The lice Damalinia reduncae and Linognathus fahrenholzi were present on the reedbuck from each locality. In addition 3 red duiker, Cephalophus natalensis, and 2 bushbuck, Tragelaphus scriptus, from the Charter's Creek Nature Reserve plus 2 impala, Aepyceros melampus, from the St Lucia Game Park were examined for ixodid ticks. The red duiker were infested with 3 tick species and the bushbuck and impala with 4 each. PMID- 3353097 TI - Experimental transmission of jaagsiekte (ovine pulmonary adenomatosis) to goats. AB - Jaagsiekte was successfully transmitted to at least 2 out of 6 goats inoculated intratracheally with partially purified jaagsiekte retrovirus. Multiple, small, well circumscribed nodules found in the lungs consisted of typical papilliform proliferations of neoplastic Type II epithelial cells. Histological evidence of a mild interstitial pneumonia in 4 of the experimental animals can probably be attributed to a contaminating lentivirus in the jaagsiekte retrovirus preparation, as suggested by the seroconversion of the animals. PMID- 3353098 TI - Isolation of pure Babesia equi and Babesia caballi organisms in splenectomized horses from endemic areas in South Africa. AB - Both Babesia equi and Babesia caballi are endemic in large parts of South Africa. Attempts were made to obtain pure local isolates of both B. equi and B. caballi for the purpose of developing serological tests to study the epidemiology of equine babesiosis in this country. The indirect fluorescent antibody test was used to screen horses for B. equi and B. caballi in an endemic area. Seven horses and 3 donkeys between 3 and 36 months of age that tested negative were subsequently splenectomized. The splenectomy operation was performed through the abdominal approach. A 100% survival rate was achieved through this method, probably because it reduced the risk involved in the operation. Blood collected from naturally infected horses and passaged in fully susceptible splenectomized horses and a donkey, under laboratory conditions, produced 2 isolates of Babesia caballi and 1 of B. equi. Microscopical and serological examinations confirmed that these were pure isolates. PMID- 3353100 TI - The pathology of chronic Drechslera campanulata toxicosis in inbred rats. AB - Cultures on autoclaved maize of the phytopathogenic fungus, Drechslera campanulata, were incorporated into diets and fed to male inbred BDIX rats. In a pilot trial, a diet containing 30% D. campanulata culture material killed 5 out of 5 rats in 15-25 days. Lesions included gastric corpus erosions, gastrorrhagia and ulcerative typhlitis. Diets containing 5% or 10% culture material induced erosive to ulcerative typhlitis and oedema and hyperplasia of the ileocaecal lymph nodes in 40 out of 40 rats. Other changes included: mass loss; normocytic, hyperchromic anaemia; leukocytosis with neutrophilia; reductions in plasma proteins, creatinine, calcium and cholesterol; elevated serum enzymes; hepatosis, nephrosis and mycoplasma-like interstitial pneumonia. No lesions were present in control rats, and their profiles were normal. Ulcerative typhlitis induced by D. campanulata in rats resembles that seen in chronic piperonyl butoxide intoxication as well as that due to single treatments of indomethacid, although small intestinal ulcers are more frequent in the latter. Overgrowth of intestinal flora may be involved in ulcer pathogenesis. The pathology of drechsleratoxicosis in rats is compared to that in sheep and goats where necrotic lesions in the forestomach and, to a lesser extent, in the caecum are characteristic findings. PMID- 3353099 TI - The clinical pathology of heartwater. I. Haematology and blood chemistry. AB - Clinical pathological studies were undertaken in 5 calves with experimentally induced heartwater. The most important findings include a progressive anaemia which may be associated with bone marrow depression and fluctuations in the total and differential white cell count, of which an eosinopenia and a lymphocytosis were the most marked. A severe drop in serum protein, especially in the albumin levels, was observed in all 5 cases. This disease is probably associated with an increased capillary permeability, as the protein content of the pericardial fluid in 1 case that died, approximated that of the serum. The osmolality of the effused fluid was also higher than that of the blood. No significant changes in the serum electrolyte levels occurred, except for total calcium levels which tended to decrease to below normal during the acute stage of the disease. Marked increases in total bilirubin were recorded. This, however, was not associated with liver pathology or haemolysis and may possibly be ascribed to a fasting hyperbilirubinaemia. Darkening of plasma colour was associated with peak rises in total bilirubin. Increases in both blood urea and creatinine levels indicate interference with renal glomerular filtration during the acute stage of the disease. PMID- 3353101 TI - Further observations on the electrophoretic characterization of South African Schistosoma mattheei and S. haematobium. AB - Eleven enzymes, which were used to compare South African S. mattheei and S. haematobium in a former study, were employed to study intraspecific variation within S. mattheei, using starch gel electrophoresis and iso-electric focusing where resolution in starch gel was poor. Acid phosphatase varied intraspecifically within S. mattheei in that the most southern population differed from the northern populations. Malate dehydrogenase also varied intraspecifically. Three populations which occur sympatric with S. haematobium had a MDH-1 allele in common with the human schistosome while an allopatric population did not. PMID- 3353102 TI - Wildebeest-derived malignant catarrhal fever: unusual epidemiology in South Africa. AB - The epidemiology of wildebeest-derived malignant catarrhal fever in South Africa differs from the worldwide accepted pattern. Here the occurrence of the disease is often not related to close contact between cattle and wildebeest, and most cases are observed during late winter and spring, when wildebeest calves are 8-10 months old. This is in contrast to the situation in Kenya and Tanzania, where most cases are encountered during autumn, when wildebeest calves are 3-4 months old. PMID- 3353103 TI - Aerobic metabolism of trehalose in the taxonomy of coagulase negative staphylococci. AB - Comparative assays demonstrated that the probability of error was 12.1% when testing the aerobic fermentation of trehalose by coagulase negative staphylococci when this carbohydrate was added to the medium prior to sterilization whereas the error was only 2.7% in media if filtered trehalose was added subsequent to steam sterilization of the medium. PMID- 3353104 TI - The use of domestic chickens as laboratory hosts of the larvae of the bont tick, Amblyomma hebraeum. AB - A comparison of attachment, engorgement and moulting success of Amblyomma hebraeum larvae fed on domestic chickens and Himalayan giant white rabbits indicates that chickens are better hosts than the rabbits. Moreover the time needed for detachment of all engorged larvae is significantly less for chickens than for the rabbits. No evidence of induced immunity was found in chickens on re infestation with larvae of A. hebraeum. PMID- 3353105 TI - [The ischiopagus tetrapus twins of Pecs]. PMID- 3353106 TI - [The effect of smoking during pregnancy on the birth weight percentile values]. PMID- 3353107 TI - [Percentage, per thousand, per ten thousand! More than 100 cases or less than 100 cases? Responsibility of the author, proofreader and publisher]. PMID- 3353108 TI - [Autoimmune origin of juvenile diabetes]. PMID- 3353109 TI - [Evaluation of ischemic heart disease and its primary risk factors by ergometric studies at the Mecsek Ore Mining Company]. PMID- 3353111 TI - [Development of home care in Vorarlberg]. PMID- 3353112 TI - [Care of the sick on its way to health care]. PMID- 3353110 TI - [Reye's syndrome: management of hyperammonemia by essential amino acid-ketoacid substitution]. PMID- 3353113 TI - [Health promotion--a challenge for everyone]. PMID- 3353114 TI - Developmental regulation of ovarian-specific Mos expression. AB - To gain better insight into the physiologic role of the Mos proto-oncogene in mice we have been studying the cell type and developmental specificity of its expression. It was previously shown that in adult mice, Mos is transcribed predominantly in ovaries and in haploid spermatids of the testes. Using in situ hybridization techniques we now show that in the ovary, Mos is expressed in oocytes, but not in somatic cells. In these analyses Mos transcripts are not detected in primary resting oocytes, but accumulate soon after the oocyte enters the growth phase. High levels of Mos RNA are present throughout oocyte growth and maturation. Mos RNA is also abundant in ovulated eggs prior to fertilization. Following fertilization, however, there is a dramatic loss of Mos RNA, as evidenced by the failure to detect hybridization in late one-cell embryos. The narrow developmental window for Mos transcription defined by this study suggests a role for ovarian Mos in one or more of the processes of oocyte growth, meiotic maturation, ovulation, or fertilization. PMID- 3353115 TI - Rapid appearance of novel phosphoproteins in the nuclei of mitogen-stimulated fibroblasts. AB - A sequential extraction procedure has been used to prepare three protein fractions from control and mitogen-stimulated [32P]-PO4-labelled fibroblasts, the first containing soluble and membrane-bound proteins, the second mainly the cytoskeletal proteins vimentin and actin, and the third, a chromatin-derived fraction enriched in histones. We describe here an analysis of the mitogen stimulated changes in the [32P] labelled phosphoprotein composition of these fractions. The most obvious changes in response to epidermal growth factor, embryonal carcinoma-derived growth factor, basic fibroblast growth factor and bombesin were the rapid appearance of 33 and 15 kDa phosphoproteins in the chromatin-derived fraction. The epidermal growth factor- and basic fibroblast growth factor-stimulated 33 kDa phosphoprotein produced similar chymotryptic peptides and was phosphorylated on serine residues. DNAse/RNAse treatment of the lysates was essential for the extraction of the 33 kDa phosphoprotein. Further, its presence could be demonstrated in preparations of conventionally purified nuclei. An in situ extraction procedure has been used to provide morphological verification of the sequential extraction data. The final structure containing these phosphoproteins is clearly derived from nuclei, enriched in histones, stains for DNA and appears by electron microscopy, to be homogenously composed of chromatin-like material. Thus, we describe here the rapid mitogen-induced appearance of novel phosphoproteins in the nucleus, raising the possibility that they may be involved in orchestrating early nuclear responses to polypeptide growth factors. PMID- 3353116 TI - 'To do good' is purpose of PMS Trust. PMID- 3353117 TI - Revenue Act of 1987 affects physicians. The Health Care Group. PMID- 3353118 TI - A survey of cervical lymph node biopsies. PMID- 3353119 TI - Nonoperative management of hepatic injury. PMID- 3353120 TI - The care of SCI patients in the developing nations--can we stem the rot? AB - The aims, objectives and results of the Madras Paraplegia Project at the Government General Hospital, Madras is presented. Eight hundred and forty four Spinal Cord Injury (SCI) patients have been treated in 8 years and 4 months. The Madras Model offers an alternative strategy for the total care of SCI patients. The merits and drawbacks are highlighted. The results to date commend replication of the model in areas of the world where the services for SCI Care are meagre or non-existent. PMID- 3353121 TI - Spinal cord injuries in Enugu, Nigeria--preventable accidents. AB - This is a review of 72 patients who were treated for Spinal Cord Injuries in the University of Nigeria Teaching Hospital, Enugu, Nigeria, during the period January 1980 to January 1985. There were 20 patients who had tetraplegia as a result of their injuries and 52 with paraplegia. All the patients were treated conservatively. The catchment area of the hospital is in the rain forest belt of West Africa where tall palm trees grow. Palm tree climbers use jigs which are woven from palm fronds. The climbing jigs are prone to snapping during periods of low humidity between the months of November and March. During this period of the year the tensile strength of the jigs is greatly reduced. Our experience is that the commonest cause of spinal cord injury is a fall from palm trees. Climbers should be educated about the time related jig failure, falls and subsequent spinal cord injury. Alternative sources for stronger materials for weaving jigs, and increased growing of shorter species of palm trees from which harvesting of palm nuts take place at ground level are advocated. Other causes of spinal cord injuries and preventive measures are discussed. PMID- 3353122 TI - A clinical review of the adult hip guidance orthosis (Para Walker) in traumatic paraplegics. AB - Twenty Adult traumatic paraplegics with neurologically complete lesions between C8 and T12 have ambulated using a ParaWalker (adult hip guidance orthosis), for a minimum of 6 months at home. At follow up, on average 20 months from the date of issue of the orthosis, 17 patients (85%) were still regularly using their ParaWalker. Patients achieved independent use of the orthosis and low energy ambulation both indoors and outdoors on a variety of surfaces. A new classification of adult paraplegic ambulation using an orthosis is described. PMID- 3353123 TI - Long-term follow-up of spinal cord injury patients with vesicoureteral reflux. AB - The medical records of 32 spinal cord injury patients with 43 vesicoureteral refluxes admitted to our hospital from 1970 to 1982 were retrospectively reviewed. These patients were followed yearly with pyelograms together with cystograms or cystourethrograms. Many of these individuals were on an indwelling Foley catheter at the time reflux was detected, indicating that free urinary drainage such as a Foley catheter did not prevent reflux formation. Further, the majority of refluxes developed 1-2 years post-injury, and some disappeared spontaneously without causing any damage to the urinary tract. However, the indwelling Foley catheter was ineffective for reflux treatment because in the long run it did not prevent progression of vesicoureteral reflux and did not protect the refluxing kidney from damage. We also noticed that the incidence of reflux was statistically higher in patients with complete spinal lesion than in those with incomplete neurological dysfunction. This incidence was also higher in individuals with an upper motor neuron lesion. PMID- 3353124 TI - Fever and thromboembolic disease in acute spinal cord injury. AB - Thromboembolic Disease (T.E.D.) is a major cause of morbidity and mortality in the first few months following spinal cord injury. The purpose of this three year retrospective study is to delineate the previously poorly described role of fever as both a common component of T.E.D. manifestation and, on occasion, the sole presenting sign of an otherwise occult T.E.D. process. We reviewed 148 consecutive admissions to the Southeastern Michigan Spinal Cord Injury System (1982-1985). Ten patients with documented T.E.D. were found and extensively reviewed; 3 had inadequate documentation of clinical manifestations and 1 patient was found from venography to have a non-acute thrombosis. Of the remaining 6 cases, all had fever as a sign, and 4 of these patients had fever as the sole presenting sign. Full fever work-ups were performed in each case and no other source for fever could be found. Fever spikes occurred most commonly at night, with a maximum temperature of 100.2 degrees F (oral) to a high in one case of 103.0 degrees F (oral). All fevers resolved within the first week of adequate anticoagulation therapy. These findings indicate that fever may be the earliest and, possibly, only clinical sign of an otherwise occult T.E.D. process. PMID- 3353125 TI - Heart rates of participants in wheelchair sports. AB - The relative stress of participation in wheelchair basketball, volleyball, tennis, and racquetball were determined by monitoring the heart rates of wheelchair athletes. Heart rates were recorded for 5 seconds every 30 seconds during monitoring sessions of 10 min or longer under game or practice conditions. Subjects were volunteer paraplegic athletes with lesions below T5 or with equivalent disability according to an international sport classification system. Average heart rates were 89 beats/min for tennis 'practice', 96 for racquetball 'practice' 107 for volleyball 'practice', 114 for volleyball 'game', 127 for tennis 'game', 129 for basketball 'practice', 135 for racquetball 'game', and 149 for basketball 'game' conditions. The percentage of time when heart rates were above 140 beats/min, followed the same pattern as the average heart rates and ranged from 0 to 62%. PMID- 3353126 TI - Tumour or infection? Misleading spinal radiographs. AB - Radiological appearances alone are often insufficient to make a precise diagnosis of spinal pathology, and should be supplemented by appropriate investigations, which ideally should include histological and bacteriological examination of the diseased tissues. PMID- 3353127 TI - Evolution of post-traumatic cervical syringomyelia: case report. AB - A patient with complete post-traumatic paraplegia below T6 developed urinary problems and late secondary syringolmyelia. The concordance between the appearance of micturition difficulties and the first sensory symptoms leads us to discuss the role of important and repeated efforts to obtain reflex micturition, during the development of post-traumatic syringomyelia. PMID- 3353128 TI - Inbred mice infected with Plasmodium yoelii differ in their antimalarial immunoglobulin isotype response. AB - Antibodies are known to be important in mediating malarial immunity, but the influence of the various immunoglobulin isotypes on parasite elimination is unclear. The purpose of this study was to provide basic information on the induction of isotype expression in genetically different mice during primary malaria. Parasitaemias and the serum antimalarial IgM, IgG1, IgG2, IgG3 and IgA antibody titres measured in a radioimmunoassay were followed in outbred and 11 inbred strains of mice infected with 17XNL Plasmodium yoelii. Severity of infection, as judged by length of infection, peak parasitaemias and death, was found to differ between the strains. All strains developed rapid IgM responses, but only 3/11 inbred strains produced significant antimalarial IgG1 levels during primary infection. All strains produced an IgG2 response, which developed slightly more quickly in strains with the least severe courses of malaria. A large variation in the IgG3 response was noted between strains. In general, IgG3 antibodies were the first IgG-isotype to appear in serum. They were detected as early as day 8 in strains that developed mild infections but were not present until around day 20 in strains with the most severe cases of malaria. Only one strain produced detectable antimalarial IgA antibodies. These results show that different patterns of isotype expression are induced in inbred strains of mice during primary P. yoelii infection. PMID- 3353130 TI - Suppression of mucosal mastocytosis by Nematospiroides dubius results from an adult worm-mediated effect upon host lymphocytes. AB - Infections with the nematode Nematospiroides dubius fail to elicit mucosal mast cell (MMC) responses in the intestines of host mice, and suppress MMC responses generated by heterologous infection. Larval N. dubius have the capacity to prime for mastocytosis, and to elicit this response in primed mice during a challenge, but only if adult worms are prevented from developing, either by anthelmintic treatment or by irradiation of the larvae themselves. The suppressive effect of the adult stage was confirmed in experiments where such worms were implanted directly into the intestines of mice primed by exposure to irradiated N. dubius larvae or concurrently infected with Trichinella spiralis. Data on the mechanisms underlying this suppressive effect were obtained from experiments involving the adoptive transfer of mastocytosis by mesenteric lymph node cells (MLNC) from T. spiralis infected mice. When MLNC were taken from mice infected concurrently with both T. spiralis and N. dubius no enhanced mastocytosis was seen in recipients after challenge with T. spiralis. Exposure of MLNC from T. spiralis infected donors to the presence of adult N. dubius after transfer did not reduce the adoptively transferred response. The response was also unaffected when MLNC from adult N. dubius infected mice were simultaneously transferred with MLNC from T. spiralis donors. It is concluded that the suppressive effect of adult N. dubius upon the expression of mucosal mastocytosis acts upon the generation of lymphocytes capable of promoting the development of MMC from precursor cells. PMID- 3353129 TI - Immunity to coccidiosis: adoptive transfer in NIH mice challenged with Eimeria vermiformis. AB - The development of a reliable model for the adoptive transfer of immunity to coccidiosis (infection with Eimeria vermiformis in NIH mice) is described. More than 10(8) of a mixture of spleen and mesenteric lymph node (MLN) cells, given either intravenously or intraperitoneally, were required to transfer a significant degree of protection. Dividing cells, present in the donors at 10 or 14 days after priming, but not at 5 or 19 days, were shown to be the effectors. When examined separately, MLN cells were found to be superior to spleen cells, and the injection of as few as 5 x 10(7) was capable of substantially reducing the oocyst output from a challenge inoculum. The recipients of cells from primed mice had earlier, and sometimes higher, titres of specific antibodies in the serum but, overall, there was no correlation between these titres and protection. Further characterization of the cells responsible for adoptively transferring immunity to this infection should now be possible. PMID- 3353132 TI - The most dangerous disease of childhood. PMID- 3353131 TI - Cytotoxic activity of rat granulocytes against Mesocestoides corti. AB - Rat eosinophils or neutrophils were purified from peritoneal washings which had been enriched either for eosinophils by infection with the parasite Mesocestoides corti or by intravenous injection with Sephadex G200 particles, or for neutrophils by the intraperitoneal injection of glycogen. Neither eosinophils nor neutrophils attached to or damaged live M. corti parasites in vitro although they did lyse chick erythrocytes in the presence of rat anti-chick red blood cell antibody, with the neutrophils showing the highest level of cytotoxicity and the eosinophils from the infected rats the lowest. Neutrophils gave a specific antibody-dependent cytotoxic response to chick erythrocytes coated with solubilized M. corti extract, a response not seen with eosinophils. The cytotoxicity shown by neutrophils could not be blocked by adding eosinophils or sera obtained from chronically infected rats although it was reduced by incubating the neutrophils with cell-free supernatants obtained from the spleen cells of infected rats following stimulation with solubilized parasite extract in vitro. Eosinophils from infected rats expressed fewer membrane Fc receptors for antibody than did neutrophils or eosinophils from uninfected animals. Incubation of neutrophils and eosinophils from uninfected rats with the immune spleen cell supernatants reduced Fc receptor expression to levels similar to those seen with eosinophils from infected animals. These same supernatants had no effect on the expression of granulocyte complement receptors. It is suggested that infection of rats with M. corti can lead to the production of an antigen-specific suppression capable of impairing the antibody-dependent activity of granulocytes in vitro. PMID- 3353133 TI - Molecular biology and high tech cancer therapy. PMID- 3353134 TI - School-based clinics: impact on teenage pregnancy prevention. PMID- 3353136 TI - Technology dependent children in the home. PMID- 3353135 TI - Newborn outcomes with maternal marihuana use in Jamaican women. PMID- 3353138 TI - Cluster care nursing: Maricela's story. PMID- 3353137 TI - Exclusively breast-fed infants: growth and caloric intake. PMID- 3353140 TI - Networking across professional lines. PMID- 3353139 TI - Juvenile rheumatoid arthritis--parent support group: do parents perceive a need? PMID- 3353143 TI - Orphan drugs. PMID- 3353142 TI - The surgical neonate: principles of nursing management. PMID- 3353141 TI - Communication: a two-way street. PMID- 3353144 TI - Addressing legal issues associated with AIDS. PMID- 3353145 TI - Involuntary smoking--children in crisis. PMID- 3353146 TI - Using the home inventory to assess the family environment. PMID- 3353147 TI - Invited commentary on the review article by S.G.Miles, W.A. Cumming and J.L.Williams: Pneumatic reduction of ileocolic intussusception in children. Some thoughts on pneumatic reduction of intussusception. PMID- 3353148 TI - Primary bone tumours of the hand. Report of 21 cases. AB - Twenty-one primary bone tumours of the hand in children from 8 paediatric hospitals are reported. Osteochondromas and enchondromas were not included. Our material consisted of 16 patients with common tumours (3 Ewing's sarcoma, 5 aneurysmal bone cyst, 6 osteoid osteoma and 2 epidermoid cyst) and 5 patients with uncommon tumours (osteoma, simple bone cyst, haemangiopericytoma, capillary angiomatous tumour and benign ossifying fibroma or osteoblastoma). The X-ray diagnosis of the common tumours should have high concordance with histology, whereas that of uncommon tumours is much more difficult and uncertain. The characteristic features of Ewing's sarcoma are stressed as all our children with this tumour had a delayed diagnosis and a fatal outcome. Differential diagnosis with other short tubular bone lesions of the hand - specifically osteomyelitis - is discussed and the possibilities of microscopic diagnosis are stressed. PMID- 3353149 TI - The trichothiodystrophy syndrome of Pollitt. AB - Trichothiodystrophy, or sulphur-deficient brittle hair, is a clinical marker for a syndrome that consists primarily of cystine (and hence sulphur)-deficient brittle hair, nail dysplasia, mental and physical retardation and decreased fertility. The radiological aspects of this syndrome have received scant mention in the literature. I describe a 5-year-old boy whose skeleton exhibits axial osteosclerosis and peripheral osteopenia which is similar to two other previously described cases. PMID- 3353150 TI - Solitary hepatic Burkitt lymphoma presenting as acute pancreatitis. PMID- 3353151 TI - Diffuse neonatal gastric infarction. AB - Diffuse neonatal gastric infarction can be a devastating complication of invasion of the gastric wall and vessels by fungi colonizing the gastric mucosa. Even in the presence of extensive transmural necrosis, however, the radiographs do not necessarily show evidence of gastric mucosal abnormality. Instead, plain films and positive contrast studies may erroneously suggest a mechanical gastric outlet obstruction. Ancillary evidence of a devitalized viscus in a baby who appears to have complete gastric outlet obstruction should suggest the diagnosis of gastric infarction. PMID- 3353152 TI - Juvenile xanthogranuloma of the kidney. AB - Juvenile xanthogranuloma is a benign histiocytosis of infancy and childhood characteristically involving the skin, the eye, and, rarely, the lungs, liver and mesothelial structures. This report documents the first known case of renal involvement which is demonstrated by ultrasound and computed tomography. PMID- 3353153 TI - Ovarian torsion: an unusual cause of bilateral pelvic calcifications. AB - Ovarian calcification in children is rare, usually unilateral, and in most cases implies tumor involvement. A case of bilateral ovarian torsion with calcification that might mimic neoplasm is presented along with a literature review. PMID- 3353154 TI - Explanation of confusion in recent article. Postnatal resolution of large ovarian cysts detected in utero. PMID- 3353156 TI - Pulmonary emphysema in a neonate with Marfan syndrome. PMID- 3353155 TI - Sickle cell anemia and cholelithiasis. PMID- 3353157 TI - Immunoreactive somatomedin C/insulin-like growth factor I in urine from normal subjects, pituitary dwarfs, and acromegalics. AB - Using antibodies to somatomedin C/insulin-like growth factor I (SmC) produced in rabbits using the recombinant hormone, we have developed a radioimmunoassay for SmC. Gel-chromatography of urine revealed that the vast majority of immunoreactive SmC was eluted coincident with 125I-SmC and a small portion eluted with fractions having a mol. wt. range of 30,000-40,000. The SmC concentration in urine was determined by radioimmunoassay after ammonium sulfate extraction. Values did not ordinarily exceed 1 ng/ml. When the values from normal subjects were expressed as ng/mg creatinine, high levels were observed in the neonatal period. These values fell rapidly in infancy, declined more gradually in childhood, were slightly elevated at early puberty, and were lowest in adulthood. Urine SmC concentrations in 15 pituitary dwarfs were lower than the averages obtained from agematched control subjects, and six of them showed abnormally low values. Three patients with active acromegaly had high SmC values in urine. In conclusion, 1) SmC, mainly of monomeric form, was immunologically detected in urine. 2) Radioimmunoassay for urine SmC revealed that values varied considerably with age in normal subjects and were partially dependent on the human growth hormone status. However, the full meaning of the findings remains to be elucidated. PMID- 3353158 TI - The effect of tin-protoporphyrin on bilirubin conjugation and production in cholestatic rats. AB - Tin-protoporphyrin (SnP) is actively being investigated for treatment of exaggerated neonatal hyperbilirubinemia. Because both bilirubin conjugation and excretion are immature in the human newborn, we investigated the effect of SnP on bilirubin-conjugating mechanisms and the efficacy of SnP in suppressing serum bilirubin levels in adult rats made cholestatic by surgical bile duct ligation. Male Sprague-Dawley rats received SnP (100 mumol/kg body weight) subcutaneously either 24 h before or 24 or 48 h after bile duct ligation. Serum and urine specimens were collected 72 h after bile duct ligation and analyzed for bilirubin and its conjugates. As compared to a control group that received bile duct ligation and a sodium phosphate buffer injection, all SnP-treated animals had a significant lowering of total serum bilirubin levels. No differences in the distribution of serum bilirubin mono- and diconjugates in serum or urine samples were observed. However, the concentrations of covalently linked bilirubinprotein conjugates were significantly higher in the control cholestatic rats when compared to the SnP-treated animals. SnP effectively lowers serum bilirubin levels in rats with an impaired biliary excretory pathway for SnP. There was no adverse effect on bilirubin conjugation and no observable toxicity. PMID- 3353159 TI - Long-term monitoring of treatment with recombinant human growth hormone by serial determinations of type III procollagen-related antigens in serum. AB - Inasmuch as recombinant human growth hormone is now more generally available for the treatment of different types of short stature, there is a need for better short-term indicators of treatment success. In healthy children, serum concentrations of antigens related to the aminoterminal propeptide of type III procollagen (P-III-NP) closely follow the growth velocity curve. P-III-NP was measured longitudinally in 20 children with growth hormone deficiency during 6 months of human growth hormone substitution therapy. Two different radioimmunoassay systems were used; one recognizes predominantly the intact propeptide showing a lesser affinity to a smaller monomeric peptide (RIAgnost assay), while the other assay detects both forms equally (FAB assay). These results were compared to the growth response [median 5.6 (0.4 to 13.9) cm in 6 months] and to other established growth correlated parameters (somatomedin C, alkaline phosphatase). A relatively better growth response correlated significantly with high pretreatment P-III-NP (RIAgnost assay) values (r = 0.56) and delayed bone age (r = -0.70). A combination of these parameters in multiple regression analysis increased the cumulative prediction value to above 60% (r2 = 0.61). On the other hand, P-III-NP (FAB assay) values proved to be best in monitoring treatment, correlating with the individual growth rate during the first 3 months (r = 0.40; p less than 0.05), during the consecutive 3 months (r = 0.66; p less than 0.001), and during the total 6-month period (r = 0.46; p less than 0.05). All other parameters showed associations to growth only during some treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353160 TI - Enhanced uptake of taurine by basolateral plasma membrane vesicles isolated from developing rat liver. AB - Inasmuch as taurine biosynthesis is decreased during early postnatal life, an efficient mechanism for taurine uptake by the liver must be present to maintain intracellular stores of this beta-amino acid. Therefore, basolateral liver plasma vesicles prepared from 14-day and adult rats were used to examine taurine transport during development. For both age groups, the presence of an inwardly directed Na+ gradient stimulated the initial rate of taurine uptake and caused a transient accumulation of taurine above equilibrium. For all time points before equilibrium, taurine uptake was significantly greater with membrane vesicles from 14-day compared to adult rat livers. In contrast, no age-related differences in Na+-independent uptake as measured with a K+ gradient were detected. With equal intravesicular and extravesicular Na+ concentrations, taurine uptake remained significantly greater in the younger age group. For both age groups, Na+ dependent taurine uptake was saturable but the apparent Km and Vmax for Na+ dependent taurine uptake were significantly greater in membrane vesicles from 14 day compared to adult rats. These findings suggest that an increased number of functional carriers for taurine are present in developing compared to adult basolateral plasma membrane perhaps reflecting the needs of the immature liver for this essential nutrient. PMID- 3353161 TI - Effects of epinephrine on the renal vascular bed of fetal, newborn, and adult sheep. AB - The renal hemodynamic response to renal artery infusions of epinephrine were compared in conscious and chronically instrumented fetal (125-139 days gestation; term 145 days), newborn (5-13 days postnatal), and nonpregnant adult sheep. Epinephrine produced similar dose related decreases in renal blood flow velocity in all three groups. The mean estimated concentration of epinephrine in renal blood producing a 50% decrease in renal blood flow velocity, ED50, was 0.008 microgram/ml. Epinephrine infusions during renal alpha-adrenoceptor blockade with phentolamine produced increases in renal blood flow velocity that were of greater magnitude in fetal compared to newborn and adult sheep. The maximal increase in renal blood flow velocity observed were 57 +/- 11%, 22 +/- 3%, and 18 +/- 3% in fetal, newborn, and adult sheep, respectively (p less than 0.001). This vasodilation produced by epinephrine during alpha-adrenoceptor blockade was completely inhibited by ICI 118,551, a beta 2-adrenoceptor antagonist. Inhibition of renal vascular beta-adrenoceptors with propranolol in fetal sheep did not enhance alpha-adrenoceptor-mediated renal vasoconstriction with epinephrine infusions. Results of the present study demonstrate similar renal vasoconstrictor responses to renal artery infusion of epinephrine in fetal, newborn, and adult sheep. In contrast, the renal vasodilator responses observed with epinephrine infusions during renal alpha-adrenoceptor blockade were greater in fetal compared to newborn and adult sheep. However, epinephrine-mediated renal vasoconstriction was not enhanced by blockade of beta-adrenoceptors in fetal sheep. PMID- 3353162 TI - Influence of repeated upper airway obstruction on the arousal and cardiopulmonary response to upper airway obstruction in lambs. AB - Experiments were done on five lambs to determine if repeated obstruction of the upper airway influences the arousal and cardiopulmonary response to upper airway obstruction. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial hemoglobin oxygen saturation. A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. The animals were studied after a 3-day recovery period. During a study, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that air flow could be obstructed by inflating the balloon. The balloon was inflated each time the animal went to sleep for approximately 100 consecutive epochs (17 to 30 h) and the time to arousal and the arterial hemoglobin oxygen saturation at arousal were recorded. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred from both sleep states during upper airway obstruction but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial hemoglobin oxygen saturation were significantly increased with repeated upper airway obstruction only during active sleep. Inasmuch as it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanisms of the state-specific changes in the arousal response to upper airway obstruction are warranted. PMID- 3353163 TI - Thyroxine inner ring monodeiodinating activity in fetal tissues of the rat. AB - We studied thyroxine (T4) inner ring monodeiodinating activity (5-MA) in various tissues of fetal, maternal, and adult male rats. Tissue homogenates were incubated with 0.26 microM T4 in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA and 400 mM dithiothreitol (final volume 0.7 ml) for 10 min at 37 degrees C; the 3,3',5'-triiodothyronine (rT3) generated was measured by radioimmunoassay of ethanol extracts of incubation mixture and the result was corrected for rT3 degradation during incubation. Compared to maternal tissues, T4 to rT3 5-MA in the 14-day-old fetus was increased about 70 times in skeletal muscle (mean +/- SEM, velocity, 5.4 +/- 0.9 versus 0.08 +/- 0.01, pmol rT3/h/mg protein); approximately 8 times in intestine (0.72 +/- 0.17 versus 0.09 +/- 0.03);and approximately 4 times in cerebral cortex (19 +/- 0.5 versus 4.5 +/- 0.9), while it was similar in skin (3.2 +/- 0.48 versus 2.6 +/- 0.52). Hepatic T4 5-MA approximated 1.1 +/- 0.63 in the 14-day-old fetus; it could not be measured reliably in maternal or 19-day fetal tissue because of extensive (greater than 90%) degradation of rT3 during incubation. Relative to mother, T4 5-MA in 19-day fetal tissues was increased approximately 30-fold intestine, approximately 20 fold in skeletal muscle, and approximately 6-fold in cerebral cortex while it was similar in skin. The T4 5-MA in maternal rat tissues did not differ significantly from corresponding values in adult male rat, except skin, where it was lower in the mother rat (2.6 +/- 0.52 versus 4.6 +/- 0.61, p less than 0.05). In summary, relative to adult tissues T4 5-MA is exceedingly active in several fetal tissues, most notably in skeletal muscle followed by intestine and cerebral cortex. PMID- 3353164 TI - Developmental hemodynamic changes in rat embryos at 11 to 15 days of gestation: normal data of blood pressure and the effect of caffeine compared to data from chick embryo. AB - We attempted to measure arterial blood pressure of the rat embryo. The embryo was excised within the uterus and immersed in Hanks' solution at 37 degrees C. The uterus wall and yolk sac were opened to expose the umbilical vessels. The umbilical artery was punctured with a glass micro-pipette, and blood pressure was measured by using a servo-null micro-pressure system. The mean blood pressure was 0.27 +/- 0.05 mm Hg in the embryo at the 11th day of gestation (n = 7), 0.48 +/- 0.03 mm Hg in the 12-day embryos (n = 19), 1.3 +/- 0.08 mm Hg in the 13-day (n = 11), and 2.6 +/- 0.1 mm Hg in the 15-day embryos (n = 10). Heart rate was 84 +/- 11 in 11-day, 122 +/- 3 in 12-day, 192 +/- 7 in 13-day, and 198 +/- 5 in 15-day embryos. These parameters were stable within 10 min after the excision. A comparison of the data with those of the chick embryo of comparable developmental stages revealed that the blood pressure was lower in 11- and 12-day rat embryos than in the chick embryo of Hamburger-Hamilton stages 18 and 21, but this was reversed in the later stages. In the stage 21 chick embryo, intravenous administration of caffeine (60 +/- 9 mg/kg embryo weight) induced an increase in blood pressure by 11 +/- 3% (n = 8), but did not result in a significant increase in dorsal aortic blood flow (6 +/- 6%, n = 9) or in heart rate. In contrast, caffeine (62 +/- 3 mg/kg) increased the heart rate by 8 +/- 2% (n = 10) without changing the blood pressure in the rat embryo of day 12. The velocity of blood flow in the truncus was measured by a pulsed Doppler flowmeter. Caffeine injection increased the mean velocity by 21 +/- 8%). Herein we indicate that measurement of blood pressure in the rat embryo is feasible, but with some limitations, and that there may be qualitative hemodynamic differences between the rat and chick embryos. PMID- 3353165 TI - Alterations in cerebral blood flow and phosphorylated metabolites in piglets during and after partial ischemia. AB - Ventilated piglets were studied before, during (15 min), and after (90 min) hemorrhagic hypotension to correlate a 60% reduction in cerebral blood flow with cerebral energy state using radiolabeled microspheres (n = 12) and in vivo 31P nuclear magnetic resonance spectroscopy (n = 11). Cerebral blood flow (ml.min 1.100 g-1) decreased during hypotension (98 +/- 28 to 41 +/- 28, p less than 0.05), increased at 5 min postreperfusion (131 +/- 53, p less than 0.05), and returned to control values by 90 min postreperfusion. Cerebral O2 uptake was reduced during partial ischemia, remained depressed 5 min postreperfusion, and increased to within 20% of control values at 90 min postreperfusion. Relative to control, hypotension was associated with decreased (p less than 0.05) phosphocreatine (62 +/- 11%), phosphocreatine/inorganic phosphate ratio (41 +/- 10%), and nucleoside triphosphate (82 +/- 12%) while inorganic phosphate increased (155 +/- 32%, p less than 0.05). During ischemia intracellular pH dropped from 7.06 +/- 0.07 to 6.59 +/- 0.31 (p less than 0.05) and the cerebral arteriovenous difference of glucose increased. Phosphorylated metabolites returned to within 10% of control 15 min after blood reinfusion and remained constant thereafter. Based on calculations of ATP synthesis and utilization rates during control and hypotension, we speculate that the rate of energy utilization of the brain during ischemia is reduced 18-49% relative to the control utilization rate. PMID- 3353166 TI - Portal venous and aortic glucose and lactate changes in a chronically catheterized rat. AB - A method for portal venous, aortic, and gastric cannulation in the rat is described. Changes in mean portal venous and aortic blood glucose and lactate concentrations after an intragastric infusion of d-glucose to chronically catheterized rats (after regaining preoperative weight) were compared to those of acutely catheterized rats (1 h after catheter placement). Both portal venous and aortic catheters were patent for blood sampling in 67% of rats 8 days after catheter placement and 42% after 14 days. After intragastric infusion of 10 ml of 0.29 M dextrose, mean aortic blood glucose and lactate concentrations in chronically catheterized rats increased 80 and 73%, respectively, 15 min after infusion and decreased to preinfusion concentrations by 60 min. In acutely catheterized rats, mean aortic glucose and lactate concentrations increased linearly for 60 min. The concentration differences between portal venous and aortic blood glucose and lactate concentrations in chronically catheterized rats were not significantly different than baseline differences. The portal venous glucose concentrations were significantly greater than aortic concentrations in acutely catheterized rats 15, 30, and 45 min after the glucose infusion when compared to baseline differences. These data suggest that the rate of glucose uptake and metabolism to lactate is significantly altered in acutely catheterized rats when compared to chronically catheterized animals. PMID- 3353167 TI - The effect of fasting on rat portal venous and aortic blood glucose, lactate, alanine, and glutamine. AB - Using a chronically catheterized rat model, the effect of fasting on portal venous, aortic, and venous blood concentration minus aortic blood concentration ([PV-A]) blood glucose, lactate, alanine, and glutamine concentrations was determined. It has been postulated that the intestine is a source of lactate and alanine, precursors for glycogen synthesis, in the fed state. After 48 h of fasting portal venous glucose, lactate, and alanine blood concentrations decreased by 31, 28, and 41%, respectively. Portal venous glutamine concentration was not affected by fasting. A glucose [PV-A] was not found in either fed or fasted states. Whereas the lactate [PV-A] was not present in fed rats, it was negative in fasted rats. Alanine [PV-A] was positive in fed and fasted rats. The glutamine [PV-A] was negative in fed and fasted rats. These data indicate that portal venous concentrations of the gluconeogenic precursors, lactate and alanine, decrease in fasted rats. In fasted rats intestinal utilization of lactate increases as reflected by a negative [PV-A]. Fasting did not affect alanine production by the intestine or glutamine utilization. Despite these changes with fasting, we conclude that the intestine does not appear to be able to maintain portal venous blood concentrations of gluconeogenic precursors. PMID- 3353168 TI - Fibrinogen has a rapid turnover in the healthy newborn lamb. AB - The half-lives for coagulation factors in the healthy newborn infant are not known and may be different than for the adult. We measured the half-life for fetal sheep fibrinogen and compared it to the half-life of adult sheep fibrinogen. Fibrinogen was purified from adult and fetal sheep plasma and radiolabeled with either 125I or 131I. The half-lives for these fibrinogens were determined in the adult sheep and newborn lamb. In addition, the fetal and adult sheep fibrinogens were compared by reptilase time, thrombin clotting time, sialic acid content, and the behavior of the N-glycans derived from these fibrinogens on the immobilized lectin, Sepharose-concanavalin A. Finally, the in vivo response of coinjected radiolabeled fibrinogens to increasing doses of infused thrombin was determined. The fetal sheep fibrinogen differed from the adult as indicated by a prolonged reptilase time and an increased sialic acid content (fetal: 10-11 residues/340 Kd versus adult: 8-9 residues/340 Kd). The latter was also reflected in differing chromatographic profiles for the N-glycans on Sepharose-concanavalin A. The half-lives for both the adult and fetal fibrinogen were significantly more rapid in the newborn lamb (fetal: 47 +/- 2.0 h; adult: 46 +/- 2.4 h, mean +/- SEM) than in the adult (fetal: 116 +/- 6.5 h; adult: 121 +/- 6.9 h). Finally, the adult and fetal sheep fibrinogen responded to thrombin in an identical fashion in the intact animal. In summary, both adult and fetal fibrinogen have faster half lives in the lamb compared tot he adult, despite a higher sialic acid content for the fetal fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353169 TI - Measurement of tidal volume during high frequency ventilation by impedance plethysmography. AB - Electrical impedance plethysmography was evaluated in lambs as a method of measuring tidal volume (VT). Over tidal volumes ranging from 15 to 414% of estimated dead space, and frequencies of 300 to 1000 breaths/min, correlation between VT measured by the impedance technique and VT measured by whole-body plethysmography was 0.98. Above 600 breaths/min, the correlation between the two methods was 0.94. Independent calibration of the impedance technique using a pneumotachograph at conventional rates of ventilation yielded absolute values of VT which closely corresponded to values obtained with the whole-body plethysmograph (slope = 1.05, intercept = 1.4 ml, r = 0.99). These results support the potential utility of impedance plethysmography in clinical applications of high frequency ventilation. PMID- 3353170 TI - Surface cooling rapidly induces coordinated activity in the upper and lower airway muscles of the fetal lamb in utero. AB - Stimulation of cutaneous thermoreceptors may be an important factor in the initiation of continuous breathing at birth. Maintenance of a patent airway is also important in the continuation of effective ventilation after birth, but whereas in the adult the principal pharyngeal dilator is the genioglossus muscle, in the fetus genioglossus phasic activity is not synchronous with that of the fetal diaphragm. To ascertain whether a cold stimulus that initiates continuous breathing would also induce synchronized inspiratory activity in the upper airway muscles of the fetus, we have cooled fetal lambs in utero and examined the response of the genioglossus and alae nasi muscles in relation to diaphragm activity. Deep regular breathing as recorded by diaphragmatic activity and tracheal pressure started within 1-102 s after cooling commenced and coordinated inspiratory activity was seen in the alae nasi within 2-356 s. Genioglossus activity became synchronized with that of the diaphragm within 11-356 s. Cooling was continued for 4 h but although in one fetus continuous breathing with associated inspiratory activity in the genioglossus and alae nasi muscles lasted throughout the 4-h period, in the others continuous breathing was not sustained and adaptation to the cold stimulus occurred after periods ranging from 27-218 min. The relationship between breathing, upper airway muscle activity, and sleep state passed through one or more different phases, including breathing through high voltage electrocortical activity, before the normal fetal pattern of episodic breathing restricted to the low voltage electrocortical state resumed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353172 TI - Control of thyroglobulin secretion in patients with ectopic thyroid gland. AB - Serum thyroglobulin (Tg) measurements were performed in 17 children with congenital hypothyroidism due to an ectopic thyroid gland before therapy and during follow-up. Data were analysed in four periods according to duration of therapy and compared to results obtained in a group of 51 normal children aged 1 month to 6 yr. At diagnosis serum Tg was higher than the mean normal value measured at a similar age. We observed a rapid and parallel decrease of both Tg and thyroid-stimulating hormone during the early weeks of therapy. However, Tg was always detectable in the serum of treated (euthyroid) patients. After 34 months of therapy serum Tg was 11.4 +/- 1 ng/ml, a value significantly different (p less than 0.001) from that obtained in normal controls of similar age (23.5 +/ 3 ng/ml). In nine treated children aged more than 2 yr, thyroid-stimulating hormone and Tg were increased after a brief period of decreased L-thyroxine dosage. These data indicate that ectopic thyroid tissue does not involute during thyroxine therapy and, in response to elevations of serum thyroid-stimulating hormone, can be stimulated to secrete Tg. PMID- 3353171 TI - Control of fatty acid oxidation by intramitochondrial [NADH]/[NAD+] in developing rat small intestine. AB - The oxidation of palmityl-coenzyme A and acetate to CO2 by mitochondria isolated from rat small intestine increases 10-fold at the time of weaning (18-21 days of age). Carnitine palmitoyltransferase (EC 2.3.1.21) activity is 2-fold greater in mitochondria of suckling rat intestine compared to postweaned intestine. These data indicate that carnitine palmitoyltransferase does not control the increase in intestinal fatty acid oxidation during weaning. We have previously reported that the estimated intramitochondrial [NADH]/[NAD+] as determined by the ratio of tissue levels of 3-hydroxybutyrate and acetoacetate is fivefold greater in suckling rat intestine compared to postwean animals. High intramitochondrial [NADH]/[NAD+] which is present in suckling rat small intestine is associated with a decrease in citric acid cycle activity and beta oxidation. The addition of acetoacetate causes a decrease in intramitochondrial [NADH]/[NAD+]. The oxidation of acetate and glucose to CO2 by suckling rat intestine mitochondria was stimulated by the addition of 1 mM acetoacetate. These data suggest that the lower rate of fatty acid oxidation by suckling rat small intestine is controlled by elevated intramitochondrial [NADH]/[NAD+]. PMID- 3353173 TI - Ethnic variation in blood pressure among preadolescent children. AB - As part of a study on methods for assessing diet and exercise among 163 3rd to 6th grade students, data were collected on blood pressure, diet, urinary electrolytes, aerobic activity, resting pulse, and body composition. Data were collected on a stratified sample, with almost equal numbers of children of both sexes from 3rd or 4th and 5th or 6th grades; from three ethnicities: Anglo-, Black- and Mexican-American. Three resting blood pressures were obtained using a Hawksley random zero sphygmomanometer. Data analytic procedures relied on analyses of variance and covariance to assess differences across design factors in blood pressure, with dietary sodium, resting pulse, body surface area, and energy expended as covariates. No differences were detected across ethnic groups in systolic pressures, but Mexican-American children were shown to have significantly higher diastolic fourth phase pressures than Anglo- or Black American children. Only the dietary variables differed across ethnic groups, but not in the same pattern. Differences in the covariates did not account for the difference across ethnic groups in diastolic pressures. PMID- 3353174 TI - Aluminum-associated hepatobiliary dysfunction in rats: relationships to dosage and duration of exposure. AB - Aluminum may contaminate parenteral nutrition solutions and accumulate in bone and liver of patients receiving this therapy. Although aluminum exposure is associated with low-turnover osteomalacia, there are few studies of hepatotoxicity. We therefore studied the effects of aluminum given to rats on total serum bile acid concentration and bile flow to determine if aluminum administration could produce abnormalities. Aluminum was given intravenously as follows: 5 mg/kg daily for 7 or 14 days and 1 mg/kg for 14 days. Hepatic aluminum was high in treated rats and undetectable in controls. Total serum bile acid concentrations were significantly higher in treated rats than in pair-fed controls with higher concentrations after 14 days than after 7 days. Bile flow was reduced by 33% in rats given 5 mg/kg but not in rats given 1 mg/kg. Hepatic aluminum correlated inversely with bile flow but not with serum bile acid concentration. Aluminum exposure in rats is associated with elevated serum bile acid concentration and diminished bile flow and may play a role in the pathogenesis of parenteral nutrition-induced hepatobiliary dysfunction. PMID- 3353175 TI - Cellular dehydration and immunoglobulin binding in senescent neonatal erythrocytes. AB - The life span of neonatal erythrocytes (60-80 days) is shorter than that of adult erythrocytes (120 days). We studied neonatal red blood cells separated on stractan density gradients to further characterize the aging process and to explore the possibility that senescence antigens play a role in the destruction of neonatal erythrocytes. Quantitation of membrane proteins 4.1a and 4.1b served as a marker for cell age and confirmed an enrichment for senescent red cells in the most dense layers of the gradients. Despite the shorter life span of neonatal erythrocytes, cord blood contained a larger percentage of very dense, K+-depleted red cells than did adult blood. ATP levels in dense neonatal and adult cells were decreased to 50-80% of normal values for unseparated red cells. Levels of reduced glutathione did not fall with increasing cell density. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of red cell membrane proteins showed increased membrane-associated globin in senescent neonatal cells, but such gels run without reducing agents did not show oxidative protein cross-linking. Membrane bound immunoglobulins were detected on senescent neonatal and adult red cells by the rosetting antiglobulin test. We conclude that senescence antigens are revealed during the aging process of neonatal erythrocytes, thereby labeling them for antibody-mediated destruction in the reticuloendothelial system. PMID- 3353176 TI - The ontogeny of pulmonary defenses: alveolar macrophage function in neonatal and juvenile rhesus monkeys. AB - Using the technique of bronchoalveolar lavage, we isolated alveolar macrophages (AM) from the lower respiratory tract of newborn (1-4 days of age), infant (6-10 days of age), juvenile (3-6 months of age), and adult rhesus monkeys. The AM thus obtained were assayed in vitro to determine their chemotactic, phagocytic, and candidicidal capabilities. The predominant (greater than or equal to 89%) cell type in bronchoalveolar lavage effluent in all ages was the AM. Chemotaxis, phagocytosis, and killing of Candida albicans were markedly impaired in neonatal AM as compared with those from infants, juveniles, and adults. AM chemotactic activity achieved normal adult values by 6 days of age. Phagocytosis, and to a lesser extent candidicidal activity, were significantly improved in 6-day-old animals, but adult levels were still not achieved even by 6 months of age. PMID- 3353177 TI - The effects of biosynthetic insulin-like growth factor-1 supplementation on somatic growth, maturation, and erythropoiesis on the neonatal rat. AB - Somatomedins are anabolic hormones that may stimulate growth during the perinatal period. To test this hypothesis, neonatal rats were injected with a biosynthetic somatomedin, insulin-like growth factor 1 (IGF-1) twice daily for the first 2 wk of life. Two biosynthetic IGF-1 preparations of different potency were tested as well as a preparation of human growth hormone in five litters of rats. When compared to saline-injected rats, IGF-1 injected rats had increased body weight and tail length as well as specific increases in weights of liver, brain, heart, and testes. In addition, significant increases in bone marrow erythropoietic cell precursors were apparent after IGF-1 injection. IGF-1-treated neonatal rats also exhibited precocious eye opening as a sign of epithelial cell differentiation. Five additional litters of rats received similar injections but were exposed to postnatal nutritional deprivation via artificially increasing litter size. Although IGF-1 caused stimulation of bone marrow erythropoiesis and precocious eye opening, no effects of IGF-1 on somatic or organ growth could be documented. This represents the first demonstration in vivo of the anabolic effects of IGF-1 in rapidly growing neonatal rats but suggests that nutritional sufficiency may also be necessary for the full expression of somatomedin effects. PMID- 3353179 TI - In vivo bile acid uptake from terminal ileum in cystic fibrosis. AB - The cause(s) of excessive fecal bile acid loss in cystic fibrosis (CF) has not yet been fully determined, but in vitro studies have suggested that a primary mucosal defect in ileal bile acid uptake may be of importance. To examine this mechanism in vivo, the terminal ileal uptakes of taurocholate and glycocholate were determined using a marker-perfusion technique in three CF infants and four controls. Normal and CF ileal conditions were stimulated by varying the taurocholate:glycocholate concentration ratio (normal 1:1, CF 1:4) and pH (normal 7.8, CF 6.0) of the perfusate. The mean bile acid uptake under normal perfusate conditions was not significantly different in CF subjects (taurocholate 0.124 mumol/min/cm ileum +/- SD 0.127, glycocholate 0.117 mumol/min/cm ileum +/- 0.114), and controls (0.142 +/- 0.164 and 0.115 +/- 0.120 respectively). Similarly, under CF conditions, bile acid uptake values in CF subjects and controls were similar. The results are not consistent with deranged ileal bile acid reabsorption being a major cause of fecal bile acid loss in CF. PMID- 3353178 TI - Acute brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide. AB - Bilirubin toxicity produces significant neurologic and audiologic sequelae. Successful therapeutic intervention requires an understanding of the timing of neural dysfunction after exposure to bilirubin. BAEP were used in an animal model of bilirubin encephalopathy to study the onset of neural dysfunction after acute injection of a sulfonamide used to displace bilirubin out of the bloodstream and into tissue. Fourteen pairs of jaundiced Gunn rats from eight litters were studied at postnatal day 18. Baseline BAEP recordings were performed in anesthetized animals; then either sulfadimethoxine or an equal volume of saline was injected into the peritoneum. Another BAEP was done immediately, and then 2, 4, and 8 h after injection. Human serum albumin was injected into an additional 10 animals after the 2-h BAEP recording to see if induced BAEP abnormalities could be corrected. The sulfonamide-treated jj rats developed increased latencies for waves II and III, and I-II and I-III interwave intervals (p less than 0.0001). The latencies were prolonged by 2 h after injection and became progressively longer at 4 and 8 h. The amplitudes of waves II and III progressively decreased at 2, 4, and 8 h (p less than 0.0001). Latency and amplitude of waves I and IV did not change. The rats injected with albumin at 2 h showed improvement of BAEP abnormalities at 8 h. These studies show that neurophysiologic abnormalities occur as early as 2 h after intraperitoneal injection of sulfadimethoxine, and are reversible with appropriate therapy. These abnormalities are hypothesized to be due to the sulfonamide driven net transfer of free, toxic bilirubin into the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353180 TI - Cerebral metabolism in the newborn lamb with polycythemia. AB - Infants with polycythemia and hyperviscosity are known to have a reduced cerebral blood flow. Eight newborn lambs were studied to determine what effect the reduction in cerebral blood flow might have on the cerebral delivery and uptake of oxygen, glucose, lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate. Measurements of cerebral blood flow, hematocrit, blood viscosity as well as delivery and uptake of the forementioned substrates were made during a control period and at 60, 180, and 300 min after an exchange transfusion with packed newborn red blood cells was performed to increase the hematocrit. Sixty min after the exchange transfusion, cerebral blood flow fell while cerebral oxygen delivery and uptake were stable. Although arterial glucose concentration remained unchanged, there was a significant fall in cerebral glucose delivery. At 180 min after the exchange transfusion, the arterial glucose concentration fell from 90 to 70 mg/100 ml causing the cerebral glucose delivery to further decrease. This resulted in a significant fall in the cerebral glucose uptake and glucose:oxygen quotient. At 300 min arterial glucose concentration remained low but a rise in cerebral blood flow resulted in a small increase in the cerebral glucose delivery and consequently the cerebral glucose uptake and glucose:oxygen quotient returned to normal. We conclude that polycythemia results in a decrease in cerebral glucose delivery and uptake during normoglycemia. PMID- 3353181 TI - Effect of salicylic acid on mitochondrial-peroxisomal fatty acid catabolism. AB - To understand the possible role of salicylic acid in the pathogenesis of Reye's syndrome, we examined its effect on the oxidative metabolism of fatty acids in the rat liver mitochondrial-peroxisomal fraction. Fatty acids of different chain lengths are oxidized in different organelles. Octanoic acid is oxidized in mitochondria, lignoceric acid in peroxisomes, and palmitic acid in both mitochondria and peroxisomes. Salicylic acid (up to 1 mM concentration) had no effect on the oxidation of [1-14C]lignoceric acid. However, at the same concentration it inhibited the oxidation of [1-14C]palmitic acid by 26% and [1 14C] octanoic acid by 42%. The apparent Ki for the oxidation of [1-14C] octanoic acid, [1-14C]palmitic acid and [1-14C]lignoceric acid were 0.27, 6.0, and 14.8 mM, respectively. This selective inhibition of mitochondrial oxidation of medium chain (octanoic acid) and long-chain (palmitic acid) fatty acids by salicylic acid may potentiate the accumulation of fatty acids in plasma in Reye's syndrome patients. PMID- 3353182 TI - The American Pediatric Society and the Society for Pediatric Research. Combined program and abstracts. Washington, D.C., May 2-5, 1988. PMID- 3353183 TI - Photophysical properties of Sn-porphyrins: potential clinical implications. AB - The photophysical properties of Sn-protoporphyrin and two of its synthetic analogues, Sn-mesoporphyrin and Sn-diiododeuteroporphyrin, were examined. All three compounds are potent competitive inhibitors of heme oxygenase, the rate limiting enzyme in the catabolism of heme to bilirubin, and can suppress completely or diminish significantly experimentally induced or naturally occurring forms of jaundice in animals or man. The results of these studies show that all three compounds have long-lived triplet states which are quenched by molecular oxygen both in solution and when incorporated in liposomes. However, the addition of quenching groups such as iodine to the porphyrin macrocycle results in a marked (approximately 60%) decrease in the triplet yield and a threefold decrease in the triplet lifetime. The triplet yield was shown to be independent of the excitation wavelength, and as a result, the metalloporphyrins were extremely poor photosensitizers when excited in the spectral region commonly used in phototherapy. In the presence of serum albumin, the triplet state of Sn protoporphyrin was not quenched by oxygen. These results indicate that Sn porphyrins can be custom designed with considerably reduced photosensitizing properties for potential clinical use as inhibitors of bilirubin production. PMID- 3353184 TI - Jaundice in the healthy newborn infant: a new approach to an old problem. AB - We measured the serum bilirubin concentrations in 2,416 consecutive infants admitted to our well baby nursery. The maximal serum bilirubin concentration exceeded 12.9 mg/dL (221 mumol/L) in 147 infants (6.1%), and these infants were compared with 147 randomly selected control infants with maximal serum bilirubin levels less than or equal to 12.9 mg/dL. A serum bilirubin concentration greater than 12.9 mg/dL was associated strongly with breast-feeding (P = .0000) and percentage of weight loss after birth (P = .0001), as well as with maternal diabetes, oriental race, decreased gestational age, male sex, bruising, and induction of labor with oxytocin. Risk ratios and the risk of jaundice were calculated for hypothetical infants in the presence and absence of these variables. These calculations show that, in certain infants, "nonphysiologic" jaundice is likely to develop and its presence in such infants might not require laboratory investigations. In others, a modest degree of hyperbilirubinemia could be cause for concern. An awareness of these factors and their potential contribution to serum bilirubin levels permits a more rational approach to the action levels used for the investigation of jaundice in the newborn. We need a new definition of physiologic jaundice. PMID- 3353185 TI - Nursing interval and maternal responsivity: effect on early infant crying. AB - In industrialized societies, the unique pattern of crying in the first three months is "unexplained" but thought to be due to different biobehavioral factors from later crying behavior. To increase the range of the feeding and caretaking behaviors hypothesized to be relevant determinants of early crying, home observations and diary records were analyzed from samples of two subcultures of American middle-class women (La Leche League and "standard care" mothers; each n = 16) differing primarily in such practices. Both during and after the early crying stage, frequently fed infants cried or fretted less often (8.1 v 15.8 episodes per hour at 2 months of age; 10.7 v 16.6 episodes per hour at 4 months of age), and fewer of them exhibited rhythmic crying behavior (four v 11 at 2 months; eight v 13 at 4 months) during observations. However, only during the early crying period at 2 months were interval between feedings and maternal response latency shown to be independent determinants of cry/fret frequency (overall r2 = .35, P = .01), each factor accounting for approximately half of the explained individual variance. Furthermore, feeding interval was the only variable associated with rhythmic crying behavior at 2 months of age (r2 = .20;P = .01). In similar analyses at 4 months, there were no significant relationships with later crying or fretting. The results suggest that, in the presence of variation in feeding practice greater than that which is typical for our society, feeding interval may be a significant factor in early (but not later) crying behavior; furthermore, this effect is independent of and additive to the soothing effect of short response latency. PMID- 3353186 TI - Neonatal circumcision and penile problems: an 8-year longitudinal study. AB - The prevalence of penile problems was examined in a birth cohort of more than 500 New Zealand children studied from birth to 8 years of age. By 8 years, circumcised children had a rate of 11.1 problems per 100 children, and uncircumcised children had a rate of 18.8 per 100. The majority of these problems were for penile inflammation including balanitis, meatitis, and inflammation of the prepuce. However, the relationship between risks of penile problems and circumcision status varied with the child's age. During infancy, circumcised children had a significantly higher risk of problems than uncircumcised children, but after infancy the rate of penile problems was significantly higher among the uncircumcised. These associations were not changed when the results were adjusted statistically for the effects of a series of potentially confounding social and perinatal factors. PMID- 3353187 TI - Infant mortality increase despite high access to tertiary care: an evolving relationship among infant mortality, health care, and socioeconomic change. AB - In this study, the determinants of an apparent increase in the infant mortality rate of an urban population with high access to tertiary neonatal care are reviewed. For a 4-year period (1980 to 1983), all infant deaths (n = 422) of the 32,329 births to residents of the City of Boston were analyzed through linked vital statistics data and a review of medical records. A significant increase in the infant mortality rate occurred in 1982 due to increases in three components of the infant mortality rate: the birth rate of very low birth weight infants (less than 1,500 g), the neonatal mortality rate of normal birth weight infants (greater than or equal to 2,500 g), and the mortality rate of infants dying during the postneonatal period (28 to 365 days). These increases were associated with inadequate levels of prenatal care. Although transient, the impact of the observed alterations in these infant mortality rate components was enhanced by a more long-standing phenomenon: the stabilization of mortality rates for low birth weight infants. This stabilization allowed the increases in other component rates to be expressed more fully than in previous years. In this report a mechanism is shown whereby fully regionalized neonatal care ultimately may confer to the infant mortality rate a heightened sensitivity to socioeconomic conditions and levels of adequate prenatal care. PMID- 3353188 TI - Enteral drug administration practices: report of a preliminary survey. AB - This study was initiated to determine whether there is sufficient variation in enteral drug administration practices in hospitalized pediatric patients to result in adverse therapeutic consequences. A survey was developed and administered to nurses from three pediatric and six general hospitals. A total of 317 pediatric nurses responded. Results of the survey confirmed that the primary responsibility for administering enteral medications resides with the nurse. It also documented that many elements in the administration of enteral medications vary significantly among nurses, although nursing personnel expressed confidence in the efficacy of their individual drug administration techniques. Further quantitative evaluations of the efficacy of practices of enteral drug administration must be performed before meaningful standardization of drug administration techniques can be accomplished. PMID- 3353189 TI - Closed chest cardiac massage in the newborn infant. AB - The recommended techniques for external cardiac compression during cardiopulmonary resuscitation of the newborn are reviewed. The American Heart Association advises the rescuer to depress the infant's midsternum with the index and forefingers. An alternative recommendation is to encircle the chest with both hands and appose the thumbs on the midsternum. The cases reported here prove the superiority of the latter maneuver over the former in improving cardiac output and systemic blood pressures. The history of external cardiac compression in infants and children is briefly reviewed, further supporting the conclusion that the technique of encircling the chest with thumbs at midsternum is more efficacious and hence the preferred approach to closed chest cardiac massage in the newborn. PMID- 3353190 TI - Pruritic rash associated with cat scratch disease. AB - Cat scratch disease is a benign, self-limited illness characterized by regional lymphadenopathy that usually occurs in association with a history of contact with a cat. Cases of cat scratch disease with skin manifestations that included erythema nodosum; erythema multiforme; erythema marginatum; and non-specific maculopapular, petechial, and morbilliform rashes have been reported. No case of pruritic rash associated with cat scratch disease has been previously reported. In fact, one authority specifically states that the rash of cat scratch disease is nonpruritic. We report a well-documented case of cat scratch disease in which the patient's principal symptom was a pruritic rash. It is possible that this rash was the result of an immunologic reaction to the infectious agent of cat scratch disease. We conclude that cat scratch disease should be included in the differential diagnosis of pruritic rashes in children. PMID- 3353191 TI - Concurrent and predictive validity of the Yale Children's Inventory: an instrument to assess children with attentional deficits and learning disabilities. AB - The Yale Children's Inventory rating scales for completion by parents were developed to improve the ability of clinicians and researchers to evaluate the school-related problems of children. The inventory consists of 11 narrow-band and two broad-band scales, the Behavioral and the Cognitive. The concurrent and predictive validity of the Yale Children's Inventory scales are reported in a school-based sample of 103 boys. External criterion variables were obtained from parents, teachers, and standardized tests administered to the children. We found that the Attention scale overlaps both broad-band domains, indicating the importance and the intrinsic relationship of attention to both behavioral and cognitive functions, which supports the Diagnostic and Statistical Manual of Mental Disorders, ed 3 nosology for disorders of attention and activity regulation. It also increases the number of children whose assessment may be enhanced by the availability of systematic parent report forms. PMID- 3353192 TI - Psychologic aspects of childhood reflex neurovascular dystrophy. AB - Psychosocial factors in 21 families with children affected by reflex neurovascular dystrophy were studied. Each family was interviewed and given a battery of standardized psychologic tests. Two distinct types of families were identified. Fifteen families showed high internal cohesion, expressiveness, and organization and low levels of conflict. Six families showed high overt conflict with low levels of family cohesion, expressiveness, and organization. In all families parental enmeshment with the patient was present. Marital discord was present in 12 families. Thirteen patients had significant school problems (ten had learning disabilities). Although most of the children were described as especially bright, only four had above average intelligence test scores. Four had a history of sexual abuse. The patients and their mothers perceived the health problem as significantly worse than did children with arthritis from whom similar scores had been obtained. Possible role models with similar symptoms were reported by ten patients. These data support the concept that childhood reflex neurovascular dystrophy is frequently a stress-related disease; the therapeutic approach to treating these children and their families must take these psychosocial factors into account. PMID- 3353193 TI - Neonatal arytenoid dislocation. PMID- 3353194 TI - Inflammatory bowel disease in a patient with nephropathic cystinosis. PMID- 3353195 TI - American Academy of Pediatrics. Annual meeting of the Section on Pediatric Urology. Summary of the meeting, Nov 1-3, 1986. PMID- 3353196 TI - American Academy of Pediatrics Committee on Adolescence: Rape and the adolescent. PMID- 3353197 TI - Palpable lymph nodes. PMID- 3353198 TI - Head circumference data. PMID- 3353199 TI - Chlamydia and suspected sexual abuse. PMID- 3353200 TI - Clinical spectrum of mucolipidosis type IV. PMID- 3353201 TI - Diagnosis of meningitis. PMID- 3353202 TI - In defense of verbal arguments. PMID- 3353203 TI - The collector's mind. PMID- 3353204 TI - Psyche in ancient Greek thought. PMID- 3353206 TI - Comparison of the in vitro dissolution properties and in vivo steady-state pharmacokinetics of two sustained-release theophylline preparations. AB - The sustained-release properties and relative bioavailability of Theolin Retard and Pharphylline Retard were studied in eight healthy adults after treatment for five days with twice daily 450 mg, respectively 425 mg. During the day-time dosing interval on the fourth and fifth day theophylline plasma concentrations were assayed by HPLC. After intake of Theolin Retard, minimum theophylline plasma concentrations were significantly higher, fluctuations in theophylline plasma concentrations were significantly smaller and t75 (the period within a dosing interval during which the plasma concentration exceeds 75% of the maximal concentration) was significantly longer than after Pharphylline Retard. Maximal concentrations and AUC values were not significantly different. For both products the plasma concentration time-curves on day 5 were significantly lower than on day 4. In vitro dissolution tests confirmed the more sustained release of theophylline from Theolin Retard. These results indicate an equal extent of absorption from the two products but better sustained-release properties for Theolin Retard. PMID- 3353205 TI - On the do not resuscitate policy. PMID- 3353208 TI - Symposium: Disposition and delivery of peptide drugs. FIP satellite symposium. Leiden (The Netherlands), September 5 and 6, 1987. Abstracts. PMID- 3353207 TI - The bioavailability of Tamoplex (tamoxifen). Part 3. A steady-state study in breast cancer patients. AB - The bioavailability of two tamoxifen preparations (Tamoplex and Nolvadex) was compared in a multiple dose two-way cross-over design in twelve breast cancer patients. The formulations were found to be bioequivalent. Mean steady-state serum levels of tamoxifen and N-desmethyltamoxifen were 133 ng/ml and 242 ng/ml, respectively, at a single daily dose of three tablets of Tamoplex 10 mg and 128 ng/ml and 248 ng/ml, respectively, at a single daily dose of three tablets of Nolvadex 10 mg. While there was a large interpatient as well as intrapatient variability in steady-state levels of tamoxifen and N-desmethyltamoxifen, their ratio appeared to be constant in the individual patient. PMID- 3353209 TI - Pharmaceutical and Biomedical Analysis Meeting. Weesp (The Netherlands), November 13, 1986. Abstracts. PMID- 3353210 TI - A standard nomenclature for structures of the kidney. The Renal Commission of the International Union of Physiological Sciences (IUPS). PMID- 3353211 TI - Respiratory changes induced by activation of testicular afferents in dogs. AB - Reportedly, more than 90% of the testicular afferents of the dog are of the polymodal type. The possible involvement of these afferents in modulation of respiration was studied using anesthetized dogs, which had been vagotomized and with both common carotid arteries ligated. Electrical stimulation of the superior spermatic nerve at an intensity of 1/5 Tc (Tc: threshold intensity for C-fiber activation) induced no substantial changes in respiration, while above 1/2 Tc it induced an increase in minute expiratory volume (VE), or a decrease followed by an increase in VE. The pattern of respiratory change was converted from the former to the latter by increasing the stimulation frequency while maintaining the same intensity. Mechanical stimulation of the testis through a stimulator with a tip of 1 cm in diameter caused an increase of VE at 200 g and a decrease followed by an increase of VE above 500 g. Intra-arterial injection of bradykinin (3 x 10(-6) M), hypertonic saline (1.5 M) and high K+ solution (180 mM) to the spermatic artery induced similar respiratory changes. Pneumograms showed a shift in end-expiratory position even at stimulus intensities without significant VE changes. Phrenic nerve recordings from some artificially ventilated dogs, revealed an prolongation of the first expiratory phase followed by augmentation of phrenic activity, mostly an increase in respiratory rate. Comparison between afferent activities and reflex respiratory changes suggests that above described two types of respiratory changes are brought about by the activities of testicular polymodal receptors. PMID- 3353212 TI - Blockade of pulmonary stretch receptors reinforces diaphragmatic activity during high-frequency oscillatory ventilation. AB - During apneic periods elicited by high-frequency oscillatory ventilation (HFOV) a tonic diaphragmatic activity was observed, contrasting with the absence of diaphragmatic activity during apnea induced by lung inflation. To clarify the mechanism underlying the persistence of the diaphragmatic activity during HFOV induced arrest of breathing the reflex responses to short periods of HFOV, and to periods of lung inflation with airway pressure (Paw) equal to the mean Paw and/or to maximal Paw during HFOV were examined both before and after the blockade of slowly adapting stretch receptors (SR) by inhalation of sulphur dioxide (SO2) in anaesthetized rabbits. In animals with intact SR, the HFOV-induced reflex apnea lasted longer than that induced by lung inflation, the associated diaphragmatic activity being in the most cases higher than the diaphragmatic activity during quiet expiration; inflation, however, completely inhibited diaphragmatic activity. After blockade of SR, spontaneous breathing continued during periods of lung inflation, i.e., the Hering-Breuer inflation reflex was abolished, whereas HFOV still led to a cessation of spontaneous breathing, the associated diaphragmatic activity even exceeding the level observed during quiet inspiration. From these results we conclude that only one part of the reflex response to HFOV is due to SR-stimulation and that in addition other vagal pulmonary receptors (irritant- and/or C-fibre-receptors) are involved. The stimulation of the latter counterbalances the concomitant stimulation of SR, giving rise to the tonic activity of the diaphragm. PMID- 3353215 TI - Deutsche Physiologische Gesellschaft. The Physiological Society. Abstracts of the joint meeting (65th meeting). 16-19 March 1988, Wurzburg. PMID- 3353213 TI - Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane. AB - In order to study the mechanism of pancreatic HCO3- transport, a perfused preparation of isolated intra- and interlobular ducts (i.d. 20-40 microns) of rat pancreas was developed. Responses of the epithelium to changes in the bath ionic concentration and to addition of transport inhibitors was monitored by electrophysiological techniques. In this report some properties of the basolateral membrane of pancreatic duct cells are described. The transepithelial potential difference (PDte) in ducts bathed in HCO3(-)-free and HCO3(-) containing solution was -0.8 and -2.6 mV, respectively. The equivalent short circuit current (Isc) under similar conditions was 26 and 50 microA . cm-2. The specific transepithelial resistance (Rte) was 88 omega cm2. In control solutions the PD across the basolateral membrane (PDbl) was -63 +/- 1 mV (n = 314). Ouabain (3 mmol/l) depolarized PDbl by 4.8 +/- 1.1 mV (n = 6) within less than 10 s. When the bath K+ concentration was increased from 5 to 20 mmol/l, PDbl depolarized by 15.9 +/- 0.9 mV (n = 50). The same K+ concentration step had no effect on PDbl if the ducts were exposed to Ba2+, a K+ channel blocker. Application of Ba2+ (1 mmol/l) alone depolarized PDbl by 26.4 +/- 1.4 mV (n = 19), while another K+ channel blocker TEA+ (50 mmol/l) depolarized PDbl only by 7.7 +/- 2.0 mV (n = 9). Addition of amiloride (1 mmol/l) to the bath caused 3-4 mV depolarization of PDbl. Furosemide (0.1 mmol/l) and SITS (0.1 mmol/l) had no effect on PDbl. An increase in the bath HCO3- concentration from 0 to 25 mmol/l produced fast and sustained depolarization of PDbl by 8.5 +/- 1.0 mV (n = 149). It was investigated whether the effect of HCO3- was due to a Na+-dependent transport mechanism on the basolateral membrane, where the ion complex transferred into the cell would be positively charged, or whether it was due to decreased K+ conductance caused by lowered intracellular pH. Experiments showed that the HCO3- effect was present even when the bath Na+ concentration was reduced to a nominal value of 0 mmol/l. Similarly, the HCO3- effect remained unchanged after Ba2+ (5 mmol/l) was added to the bath. The results indicate that on the basolateral membrane of duct cells there is a ouabain sensitive (Na+ + K+)-ATPase, a Ba2+ sensitive K+ conductance and an amiloride sensitive Na+/H+ antiport. The HCO3- effect on PDbl is most likely due to rheogenic anion exit across the luminal membrane. PMID- 3353216 TI - Managing information. PMID- 3353214 TI - Phasic changes in intracellular pH during action potentials of sheep Purkinje fibres. AB - Regulation of intracellular pH (pHi) and the relationship between H+ and Ca2+ may vary during activity. Ion-selective microelectrodes were used to record pHi during action potentials of sheep Purkinje fibres prolonged by low temperature (21 degrees C) and elevated CO2 content. Intracellular pH also was measured during changes in extracellular calcium concentration, [Ca2+]o. Cytosolic alkalinization (peak pHi change, 0.03-0.05) was observed during the long action potential plateau and transient acidification (0.01-0.02 units) upon repolarization. Potassium-induced depolarization to plateau potentials (i.e. to 15 +/- 2 mV) simulated the peak magnitude of the alkalinization. However, compensation for the alkalinization occurred at a faster rate during the action potential (8.9 +/- 4.3 nM/min) than during K+ depolarization (1.2 +/- 0.5 nM/min). In comparison, the cytoplasm acidified in resting fibres (0.06-0.07 log units) during changes of [Ca2+]o thought to increase intracellular calcium concentration. Alterations of pHi were translated into changes of proton concentration ([H+]i). Ten- to twenty-fold elevation of [Ca2+]o evoked a comparable change in [H+]i (mean increase, 5.7 nM) but oppositely directed from that during the plateau (mean decrease, 8.8 nM). The findings in resting fibres seem consistent with displacement of bound protons by Ca2+. In contrast, the initial change in pHi during the plateau is proposed to be consequent to Ca2+ release from sarcoplasmic reticulum and/or phosphocreatine hydrolysis coupled to ATP regeneration. PMID- 3353217 TI - Accessing clinical data. PMID- 3353218 TI - MERGE: a software package for generating a single data-base starting from EMBL and GenBank collections. PMID- 3353220 TI - Objective comparison of exon and intron sequences by means of 2-dimensional data analysis methods. AB - Here we advocate the use of 2-dimensional data representation in the context of the informational approach of sequence analysis (Claverie & Bougueleret (1986) Nucleic Acids Research 14, 179-196) by applying these methods to the problem of intron/exon discrimination. Two main findings are reported: i) oligonucleotide patterns complementary to the Ul small nuclear RNA are specifically avoided in exon sequences, ii) vertebrate intron sequences, to the exclusion of other eukaryotic phyla, are characterized by a peculiar distribution of CpG containing patterns. PMID- 3353219 TI - BIGPROBE: a computer program that predicts the sequence of long oligonucleotide probes with high reliability. AB - We have written a computer program, BIGPROBE, which facilitates the design of long nucleic acid probes from the partial or complete amino acid sequence of a protein. BIGPROBE relies upon information on codon usage, intercodon dinucleotide frequency, and potential probe self-complementarity. We have examined the accuracy with which the program predicts coding sequences using sample human and rat genes and probe lengths of 30-60 nucleotides. Rat probe sequences selected by BIGPROBE using either codon usage or dinucleotide frequency data alone averaged 86-92% homology with the known exons of the corresponding gene sequences. Predictive accuracy with rat gene probes could be improved to 89-94%, depending upon probe length, by applying codon usage and dinucleotide frequency data in combination. Similar accuracy was achieved for human genes. PMID- 3353221 TI - Regen: program for designing gene assembly. AB - One of the main problems in constructing synthetic genes is the incorrect hybridisation between the oligonucleotides. The problem is resolved if the sequence uniquely defines the position of the oligonucleotide in the assembled gene. This can be accomplished through the wise partition of dsDNA sequence in the fragments. We describe a program for use in designing such gene assembly. For a given DNA sequence and the approximate location of oligonucleotide boundary it generates all sets of protruding ends that share the smallest homology. PMID- 3353222 TI - Interactive molecular biology computing. AB - It is clear that the selection of the best possible algorithm for a computer program is essential for the creation of a useful tool. After this first step is taken, however, the usefulness of such a program may be greatly enhanced or impeded by the way it is implemented. We illustrate this point by describing our implementation of the well known FASTP/FASTIN algorithm in an interactive software environment. PMID- 3353223 TI - Automated sequence reading and analysis. AB - We report on a system developed by Bio-Rad Laboratories, Inc. which combines automated reading of DNA sequencing autoradiograms with comprehensive software for shotgun overlapping of the readings, analysis of the sequences derived and searching of databases. Reading is accomplished using a high speed optical scanner and pattern recognition software operating on a personal computer. Overlapping, analysis and database searching software each incorporate significant advances over prior systems. PMID- 3353224 TI - New developments at BIONET. AB - BIONET has made considerable progress in developing communication links among molecular biologists and biochemists worldwide. We describe these efforts and also note the many new enhancements to the BIONET system itself. PMID- 3353226 TI - The EMBL data library. PMID- 3353225 TI - The GenBank genetic sequence data bank. AB - The GenBank Genetic Sequence Data Bank contains nearly 15,000 entries for DNA and RNA sequences that have been reported since 1967. This paper briefly describes the contents of the database, the forms in which the data are distributed, and the services available to scientists using the GenBank database. PMID- 3353227 TI - The protein identification resource (PIR). AB - The Protein Identification Resource consists of an integrated computer system composed of a number of protein and nucleic acid sequence databases and software designed for the identification and analysis of protein sequences and their corresponding coding sequences. The PIR serves the scientific community through on-line access, distributing magnetic tapes, and performing off-line sequence identification services for researchers. PMID- 3353228 TI - PROPHET--a national computing resource for life science research. AB - PROPHET is a national computing resource tailored to meet the data management and analysis needs of life scientists working in a wide variety of disciplines, ranging from pharmacology to molecular biology. The PROPHET system offers a fully integrated graphics-oriented environment designed for the manipulation and analysis of tabular data, graphs, molecular structures, biological simulation models, and protein and nucleic acid sequences, and it includes access to molecular structure and sequence databases. PMID- 3353230 TI - Dark side of the moon? PMID- 3353229 TI - The last cigarette. PMID- 3353231 TI - The divided unions. PMID- 3353232 TI - Sisterly feelings. PMID- 3353234 TI - 3.5 million days are lost each year waiting in outpatients' departments. Are you waiting comfortably? PMID- 3353233 TI - 3.5 million days are lost each year waiting in outpatients' departments. What can nurses do about it? PMID- 3353235 TI - Point taken. PMID- 3353236 TI - Abandoned to a 'social death'? PMID- 3353237 TI - Brachial plexus injury. PMID- 3353238 TI - Far from black and white. PMID- 3353240 TI - Making sense of suctioning. PMID- 3353239 TI - Recruit and retain. Career women. PMID- 3353241 TI - Lessons in trauma. PMID- 3353242 TI - Computers in Nursing News. PMID- 3353243 TI - Computers in Nursing News. Self-help is at hand. PMID- 3353245 TI - Keeping up with Jones. Interview by Laurence Dopson. PMID- 3353244 TI - Computers in Nursing News. Counting the cost of care. PMID- 3353246 TI - Assertiveness training. Number 2. When and why non-assertive? PMID- 3353247 TI - Honourable members. PMID- 3353248 TI - Who will be in the hot seat?. Interview by David Mitchell. PMID- 3353249 TI - What the papers said. PMID- 3353250 TI - Nurses on strike: what the public thinks. PMID- 3353251 TI - The long and winding road. PMID- 3353253 TI - AIDS and the nurse. PMID- 3353252 TI - Nurses' pay: what the government said. PMID- 3353254 TI - For what they're worth. PMID- 3353255 TI - Old school ties. PMID- 3353256 TI - Child abuse. The wilderness years. PMID- 3353257 TI - Reality orientation. Does it matter whether it's Tuesday or Friday? PMID- 3353258 TI - Save the children. PMID- 3353259 TI - Reality orientation. Worth a try. PMID- 3353260 TI - Last chance for change? PMID- 3353261 TI - Reality orientation. Checking skills. PMID- 3353262 TI - Making sense of central venous pressure monitoring. PMID- 3353263 TI - Recruit and retain. Tailor-made training. PMID- 3353264 TI - A repetitive problem. PMID- 3353265 TI - A world turned upside down. PMID- 3353266 TI - Recruit and retain. Will you not come back again? PMID- 3353268 TI - Home is where the hurt is. PMID- 3353267 TI - The long goodbye. PMID- 3353269 TI - Classroom psychiatry. PMID- 3353271 TI - Quest. NT's educational supplement. PMID- 3353270 TI - Investing in health. PMID- 3353272 TI - Quest. Lighting the touch paper. PMID- 3353273 TI - Midwives' Journal. PMID- 3353274 TI - Quest. Changing the curriculum. PMID- 3353275 TI - Midwives' Journal. Crybabies. PMID- 3353277 TI - Midwives' Journal. Malaria in pregnancy. PMID- 3353276 TI - Midwives' Journal. Antenatal care--boon or bore? PMID- 3353278 TI - Working in the hothouse. PMID- 3353279 TI - Who needs merit money? PMID- 3353281 TI - Rocking the rollercoaster. PMID- 3353280 TI - Milk of human kindness? PMID- 3353282 TI - American nursing. A tale of two systems. PMID- 3353283 TI - American nursing. America the brave? PMID- 3353284 TI - American nursing. Cousins in crisis. PMID- 3353286 TI - Research in action. PMID- 3353285 TI - The case of the disappearing midwives. PMID- 3353287 TI - Milly's hip replacement. PMID- 3353289 TI - Systems of life. No. 157. Senior systems. 22. Alcohol and elderly people. PMID- 3353288 TI - Everyday ethics for nurses. An easy death? PMID- 3353290 TI - Recruit and retain. A career in nursing? PMID- 3353291 TI - Stoma care. Identifying patients' problems. PMID- 3353292 TI - Stoma care. Waste disposal. PMID- 3353293 TI - Nucleus energy. PMID- 3353295 TI - London calling? PMID- 3353294 TI - The lonely dilemma. PMID- 3353296 TI - Writing on the wall? PMID- 3353298 TI - Recruit and retain. Child's play? PMID- 3353297 TI - Trolley full of trouble. PMID- 3353299 TI - 'I just didn't want him'. PMID- 3353300 TI - Facing the challenge. PMID- 3353301 TI - Program of change. PMID- 3353302 TI - The final straw. PMID- 3353303 TI - Stoma care. Taking an holistic approach. PMID- 3353304 TI - Assertiveness training. Number 1. Understanding assertiveness. PMID- 3353305 TI - The Journal of Infection Control Nursing. PMID- 3353306 TI - The Journal of Infection Control Nursing. Bed-making and bacteria. PMID- 3353307 TI - The Journal of Infection Control Nursing. Urinary drainage systems: a new look. PMID- 3353308 TI - The Journal of Infection Control Nursing. The salt bath myth. PMID- 3353309 TI - Mucus extractors: an infection risk? PMID- 3353310 TI - The effects of a "low-risk" diet on tumor incidence in chemically induced colon cancer in rats. AB - The relationship between various dietary constituents and colon cancer has been demonstrated by previous research. We conducted a study to investigate the combined effects of several dietary constituents on intestinal tumor incidence in azoxymethane (AOM)-induced colon cancer in rats. A nutritionally adequate, "low risk" (LR) diet was formulated through nonextreme dietary manipulations of dietary fat, fiber, protein, vitamins A and E, and selenium. Seventy-two female F344 weanling rats were given three weekly subcutaneous injections of either AOM or physiological saline solution, and were maintained on either the LR or a "high risk" (HR) diet. Food consumption and body weights were monitored on a weekly basis throughout the study. Tumor incidence was determined 36 weeks following the first injection of AOM. The incidence of adenocarcinomas in the LR diet group was 4.2% compared with 29.2% in the HR diet group. There were no significant differences in the incidence of small intestinal tumors or in the incidence of benign polyps between the diet groups. The results of the study indicated a significant protective effect of the various chemopreventive dietary factors when combined in an LR diet for colon cancer. PMID- 3353311 TI - The relative validity of a retrospective estimate of food consumption based on a current dietary history and a food frequency list. AB - The relative validity of information and food consumption in the distant past was assessed by combining a dietary history (referring to the recent past) with a food frequency list (monitoring major changes over the past 12-14 years). This approach was evaluated in a study of two groups of apparently healthy elderly people (mean age 80 years) who had participated in a food consumption study 12-14 years before the start of the present study. One group consisted of 18 harbor employees who retired subsequent to the initial assessment of food intake. On the average, each member of this group had reduced his food consumption by about 1,000 kcal. The other group consisted of 46 elderly men and women who had retired before their food consumption was measured initially. This group had not markedly changed their food intake. The results showed that both groups overestimated changes in their food intake and that the systematic overestimation and random error were similar for both groups. If the men in both groups were combined to form one group, a valid ranking of subjects in small and large consumers of energy and most of the selected nutrients was possible. However, current food intake influenced the accuracy of the measurement of past food intake. PMID- 3353312 TI - Correspondence between perceptions of change in diet and 15-year change in diet reports in the Tecumseh Diet Methodology Study. AB - As part of an effort to assess the most reliable method of obtaining information about long-term dietary intake, a study was conducted of the correspondence between perception of change in diet and measured change in reported diet from 1967 to 1982. Respondents were 1,201 men and women participants in the Tecumseh Food Frequency Study of 1967-1969 who were 45-64 years of age in 1982-1983, the time of the Diet Methodology Study. Perceptions of change were obtained by asking respondents directly if they thought they currently ate each of 12 food groups more often, less often, or as often as they did during the year of their earlier interview. Measured change was obtained by subtracting each respondent's baseline frequency for each of the 12 food groups from his or her current frequency. For 10 of the 12 food groups, correspondence was found between perception of change and measured change; fats and oils added at the table and meat were the exceptions. Significant linear relationships were found between perceptions and measured change for all food groups except fats and oils. However, greatly varying coefficients were associated with terms such as more often or as often as before, thereby limiting the potential utility of combining perceptions of change with current frequencies to obtain a reliable measure of baseline frequencies. PMID- 3353313 TI - Bath PUVA treatment: lack of specific psoralen retention effect in Langerhans cells. PMID- 3353314 TI - Polymorphous light eruption and oral contraceptives. PMID- 3353315 TI - Experimental reproduction of hydroa vacciniforme lesions. PMID- 3353317 TI - Sunscreen substantivity: comparison between water and sweat resistance tests. PMID- 3353316 TI - Solar purpura--an unusual manifestation of polymorphous light eruption. PMID- 3353318 TI - Comparative pharmacokinetics of 8-MOP in serum and in suction blister fluid. PMID- 3353319 TI - Quantitative assessment of UV-induced pigmentation and erythema. AB - In this paper we present methods that we have developed to measure pigmentation in human skin. This involves the measurement of diffuse reflection spectra from human skin in vivo and referencing them to either totally depigmented skin, or the skin of the same individual if we are measuring variations in pigmentation. Changes in the pigmentary system brought about by UV radiation can be measured for each individual. Absolute measurements lead to estimates of the melanin concentration in the skin, while differential measurements lead to estimates of the quantity of additional or reduced pigment content of some skin lesions. The same instrumentation has been successfully used to assess UV-induced erythema as well as other vascular changes. The determination of the minimum detectable erythema dose can be performed even in the darkest-skinned subjects without loss of sensitivity as in the case of laser Doppler instruments. It has been shown that what is perceived by the eye as erythema is a very complex phenomenon, encompassing a large number of vascular reactions that can be studied in detail through diffuse reflection spectroscopy. Some of the possible responses are presented, as well as the contributing chromophores that have been identified so far. PMID- 3353320 TI - Biomechanical analysis of stability and fixation strength of total shoulder prostheses. AB - The Neer I (polyethylene glenoid), Neer II (plastic glenoid surface with metal backing), Cofield, and Gristina monospherical total shoulder prostheses were tested for joint subluxation resistance and glenoid component fixation strength. Synthetic glenoid models with consistent structural properties and standard under cutting geometry were used for glenoid component fixation with bone cement. It was found that joint subluxation resistance varied linearly with axial compressive force applied. Higher subluxation strength was associated with the amount of curvature of the glenoid articulating surface. Consequently, joint stability was consistently higher for the Gristina design, and all had lower resistance in the anteroposterior direction. After complete joint dislocation under high axial compressive force, the polyethylene material at the site of subluxation experienced gross plastic deformation. The fixation strength of the glenoid component was lowest for the Neer I design and highest for the Cofield design. Fatigue loading at the joint did not seem to affect the glenoid component fixation strength. In general, all glenoid components appeared to have sufficient fixation strength against normal shoulder joint forces except the Neer I design. Loosening and fracture of the plastic glenoid component may occur under excessive loads. PMID- 3353321 TI - External fixation of the proximal humerus. PMID- 3353322 TI - Archer's shoulder. Recurrent posterior subluxation and dislocation of the shoulder in two archers. AB - Two right-handed archers presented with posterior instability of the shoulder. A 19-year-old Japanese and a 26-year-old white male archer developed pain and instability of the shoulder of 6 months' duration. Both had engaged in archery for several years. Both exhibited a positive apprehension test and recurrent posterior subluxation and dislocation by flexing the arm to 80 degrees with internal rotation. Both could reduce the instability with a snap by extending the arm. For the subluxation, Neer's inferior capsular shift procedure via a posterior approach was performed. For the dislocation, a posterior bone block was added to the inferior capsular shift. The posterior capsular redundancy was marked in both cases. At 5 and 9-years follow up respectively, both were doing archery and full activities without pain. These cases are thought to be examples of how a repetitive force can cause shoulder instability. PMID- 3353323 TI - Radiologic case study. Sacroiliac joint involvement by gout and hyperparathyroidism. PMID- 3353325 TI - Carpal tunnel syndrome due to gonococcal tenosynovitis. PMID- 3353324 TI - Answer please. Hemophilic pseudotumor. PMID- 3353326 TI - The differentiation and treatment of ankle sprains. PMID- 3353327 TI - Giant cell tumor of bone. A case history and discussion. PMID- 3353328 TI - Metastatic lesions of the hand: report of a case. PMID- 3353329 TI - Detrimental effect of cement fixation in medullary area. PMID- 3353331 TI - The presence of a mass prompts one to consider a gamut of diagnoses. PMID- 3353330 TI - Avascular nonunion of a subtrochanteric femur fracture with formation of a heterotopic bone strut. PMID- 3353332 TI - Cocaine--a particularly addictive drug. PMID- 3353333 TI - Antibiotic choices for the penicillin-allergic patient. PMID- 3353334 TI - Permanent cardiac pacing for brady-arrhythmia. AB - The indications for and technology associated with permanent cardiac pacing have undergone major changes during the past decade. In contrast to the 1970s, most patients now receive cardiac pacing devices subsequent to the diagnosis of sick sinus syndrome. However, since this condition is prevalent in elderly patients, it is crucial that indications for pacing be critically evaluated and pacing recommended only for those with documented symptoms or marked abnormalities indicative of high risk for a subsequent cardiac event. This is particularly important because pacing has not been shown to influence survival in these patients. The technological advances in pacing devices during the last ten years now provide many desirable options. As a result, available pacemakers range from very simple to highly complex; accordingly, they have a wide range of prices. It is more important than ever to carefully select the appropriate pacing device for a given patient, since its cost, longevity, and required follow-up may differ greatly. PMID- 3353336 TI - Electrophysiologic studies in cardiac arrhythmia. When and why they are useful. AB - Electrophysiologic studies have contributed significantly to the improved understanding of cardiac arrhythmias. Whereas previously treatment of these arrhythmias was largely empirical, electrophysiologic studies have paved the way for a scientific approach to evaluation and management of the patient with a potentially life-threatening problem. PMID- 3353335 TI - The new antiarrhythmic drugs. How to put them to the best use. AB - Treatment of cardiac arrhythmia should be specifically aimed at symptom control or reduction in the risk of sudden cardiac death. Until recently, a limited number of antiarrhythmic drugs were available to the practicing physician, but during the last four years, seven new ones were approved. However, these drugs are complex and have different mechanisms of action and potential for adverse effects, so the safety of therapy with them continues to be debated. Although there is little doubt that many of the new drugs (particularly flecainide [Tambocor] and encainide [Enkaid]) are highly effective in suppressing ventricular premature complexes, they should be used with caution, since they also carry a potential for worsening arrhythmia (proarrhythmic effect) and congestive heart failure. Since suppression of arrhythmia has not yet been proven to reduce mortality, care must be taken in evaluating the risk-benefit ratio when prescribing therapy, particularly for patients with less malignant arrhythmias. Careful evaluation of the effects of treatment in individual patients is indicated whenever antiarrhythmic drugs are used. Until important mortality trials have been completed (eg, the Cardiac Arrhythmia Suppression Trial), therapy should be conservative and reserved for patients with severely symptomatic or malignant arrhythmias. PMID- 3353337 TI - Supraventricular tachyarrhythmias. Mechanisms, types, and management. AB - Advances in the area of clinical electrophysiology have allowed definition of the mechanisms of most forms of supraventricular tachyarrhythmias. Reentry, automaticity, and triggered activity are the three basic mechanisms. Treatment of the arrhythmias is based on frequency and hemodynamic severity. After accurate diagnosis, empirical therapy with currently available medications usually controls symptomatic supraventricular tachyarrhythmias. Nonpharmacologic therapy with permanent antitachycardia pacemakers, percutaneous catheter ablation, or surgery is indicated for selected patients with medically recalcitrant supraventricular tachyarrhythmia. PMID- 3353339 TI - Insomnia. Clinical assessment and management of the patient who can't sleep. PMID- 3353338 TI - Significance of arrhythmias in congestive heart failure. AB - Patients with CHF are commonly encountered in clinical practice. Cardiac arrhythmias, particularly complex ventricular premature contractions, often occur in these patients. The presence of ventricular tachyarrhythmia, especially ventricular tachycardia, denotes a poor prognosis. Patients with CHF already have a limited life span, and the presence of ventricular arrhythmia further increases an already high death rate. Although previous reports failed to show any significant effect of treatment on mortality in patients with CHF, results of recent studies are encouraging. Several reports have shown that treatment with angiotensin converting enzyme inhibitors and newer antiarrhythmic agents reduces the frequency of ventricular arrhythmia and decreases mortality. It is hoped that the results of these studies will be confirmed in well-controlled, large-scale, prospective trials. PMID- 3353341 TI - Nasal disorders in children. PMID- 3353340 TI - Inflammatory bowel disease. Options in office management. AB - Current therapeutic options make office management of the patient with uncomplicated left-sided ulcerative colitis or mild to moderate Crohn's disease quite feasible for the primary care physician. On the horizon are additional drugs that will enhance the physician's ability to treat patients with inflammatory bowel disease effectively, with minimal risk of side effects or toxicity. PMID- 3353342 TI - Common fractures of the extremities. How to recognize and treat them. AB - Primary care physicians are called on to see and treat a variety of orthopedic problems, including the common fractures discussed in this article. They must recognize the fractures they feel comfortable in treating and differentiate those that should be referred to someone with more experience in complex fracture care. The goal of treatment is to restore optimal function without deformity. PMID- 3353343 TI - Differentiating Crohn's colitis from ulcerative colitis. A rundown of likenesses and dissimilarities. AB - Crohn's colitis and ulcerative colitis are two distinct clinical entities with differing clinical, pathologic, endoscopic, and radiographic findings. Because of distinct differences in their response to surgical and, in some instances, medical management, clinical separation of these two unique disease states is important. Although at times diagnostic confusion may persist, thorough clinical evaluation, including the judicious use of mucosal biopsy, yields the correct diagnosis in the majority of patients. PMID- 3353344 TI - No soapsuds enemas! PMID- 3353346 TI - Peptic ulcer disease in infants and children. PMID- 3353345 TI - Anaphylactic shock. Guidelines for immediate diagnosis and treatment. AB - With the pathophysiology of anaphylaxis firmly in mind, the primary care physician can accurately diagnose and effectively treat this acute, life threatening condition. The necessary drugs and equipment must be present in the office of any physician who performs skin testing, administers immunotherapy or intramuscular antibiotics, or uses local anesthetics. The drug of choice, epinephrine, must be administered as soon as the diagnosis is made, and hospitalization is necessary to guard against recurrent anaphylaxis. Preventive measures, including identification of the offending antigen, avoidance instructions, epinephrine for self-administration, and immunotherapy should be considered for all patients. PMID- 3353347 TI - Automated blood testing in the office. PMID- 3353348 TI - Benign cystic teratoma of the lung. AB - A young man with recurrent cough and hemoptysis was found at thoracotomy to have benign intrapulmonary cystic teratoma. Although benign cystic teratomas are a common mediastinal neoplasm, they rarely occur within the lung parenchyma. Fewer than 30 cases have been reported in the literature. Occasionally, patients present with bronchiectasis, abscess, or pneumonia in addition to cough and hemoptysis. The patient in this report had little evidence of infection and recovered rapidly following surgical excision of the mass. PMID- 3353349 TI - Infections in intravenous drug abusers. What makes them different. PMID- 3353350 TI - Effect of the antioxidant N,N1-diphenyl-p-phenylenediamine (DPPD) on bromobenzene metabolism and toxicity in isolated hepatocytes. AB - Bromobenzene induced cytotoxicity in isolated hepatocytes was partly prevented by the antioxidant DPPD (N,N'-diphenyl-p-phenylenediamine). This protection did not appear to be a result of an inhibition of lipid peroxidation but rather to an inhibition of the metabolic activation of bromobenzene. The extent of DPPD dependent inhibition of cytochrome P-450 catalyzed reactions appears to depend on the substrate being metabolized. Thus, whereas cytochrome P-450 catalyzed metabolism of bromobenzene and harmine was inhibited by DPPD, the N-dealkylation of aminopyrine was not. The results presented in this paper indicate the importance of evaluating the effect of antioxidants such as DPPD as inhibitors of bioactivation prior to drawing definitive conclusions regarding involvement of lipid peroxidation in drug induced cytotoxicity. PMID- 3353351 TI - Tissue and subcellular localizations of 3H-cyclosporine A in mice. AB - The tissue and subcellular localizations of 3H-cyclosporine A after administration to mice were determined with whole-body autoradiography and scintillation counting of lipid extracts of tissues and subcellular fractions. The radioactivity was widely distributed in the body and the pattern of distribution after oral or parenteral administration was the same, except that tissue levels were generally lower after oral administration. Pretreatment of the animals with a diet containing cyclosporine A for 30 days before the injection of radioactive cyclosporine A did not change the pattern of distribution substantially. No significant radioactivity was found in the central nervous system, except for the choroidal plexus and the area postrema region of the brain. In pregnant mice no passage of radioactivity from the placentas to fetuses was observed after a single injection. 3H-cyclosporine A and/or its metabolites showed a high affinity for the lympho-myeloid tissues, with a marked long-term retention in bone marrow and lymph nodes. There was massive excretion in the intestinal tract after parenteral administration, and the liver, bile, pancreas and salivary glands contained high levels of radioactivity. In the kidney radioactivity was confined to the outer zone of the outer kidney medulla. In liver homogenates no quantitatively significant binding of 3H-cyclosporine A and/or its metabolites to cellular molecules such as proteins, DNA, phospho- or neutral lipids was found. After lipid extraction with organic solvents, almost all radioactivity was recovered in the organic phase. PMID- 3353353 TI - Effects of postpuberal castration on dopamine receptor sensitivity in the male rat brain. AB - In order to study the effects of castration of brain dopamine (DA) receptor sensitivity, the effects of apomorphine on locomotor activity and striatal DA synthesis, as assessed by the dihydroxyphenylalanine (DOPA) accumulation after NSD-1015 treatment, were examined in normal and castrated male Sprague-Dawley rats pretreated with reserpine (5 mg/kg-18 hrs). There was an enhanced locomotor response to apomorphine (0.05-0.1 mg/kg) in castrated animals, as compared to sham operated controls. Furthermore, the increase in DOPA accumulation produced by the reserpine treatment was antagonized to a greater extent by apomorphine in the castrated animals. These results indicate an enhanced DA receptor sensitivity at both pre- and post-synaptic sites. PMID- 3353352 TI - An experimental study on ethanol elimination at subphysiological temperatures. AB - Hepatocytes isolated from fed and fasted rats have been used to study the rate of ethanol elimination at different incubation temperatures. In the presence of exogenous pyruvate, hepatocytes from fed and 42 hr fasted rats, eliminated ethanol at 37 degrees by a rate of 11.6 +/- 3.4 and 6.4 +/- 0.8 nmol/min./mg of cell protein (+/- S.D.; n = 5), respectively, which are comparable to the rates obtained in vivo. The ethanol oxidation rate in cells from rats of both nutritional states correlated linearily to the incubation temperature (t = 24-37 degrees) with a temperature coefficient (Q10) of 1.8-2.3. (Q10, (= temperature coefficient) is the factor by which the enzyme activity is increased on raising the temperature 10 degrees). These findings indicate that the oxidation is not controlled by processes which involve membrane transitions in the temperature range 24-37 degrees. Our results indicate that a hypothermic individual with a body temperature of 27 degrees would have a 40-50 per cent inhibition of the ethanol elimination rate. Thus, the observed dependency of the ethanol oxidation on the body temperature has to be regarded in back-calculations of blood ethanol concentrations in forensic toxicology. PMID- 3353354 TI - Long-term effects on biotransformation of labelled choline in different parts of the rat brain induced by single choline injections. AB - The long-term effects of single choline (Ch) injections on the uptake and metabolism of a tracer dose of 3H-Ch were studied in male rats. Choline was administered as a threshold infusion to obtain convulsions 10 and 4 weeks before sacrifice (group 1). At a single threshold infusion of choline 4 weeks before sacrifice no convulsions were induced in 50% of the animals in a second group (group 2--) whereas convulsions were induced in the remainder of the animals in this group (group 2+). Group 3 contained control animals. One min. after administration of a tracer dose of 3H-Ch the animals were sacrificed and examined for 3H-total activity, 3H-Ch, 3H-acetylcholine (3H-ACh) and 3H-phosphorylcholine (3H-PhCh). These activities were determined in three parts of the brain (cortex, striatum, midbrain + medulla oblongata). In the cortex a significant negative correlation between brain weight and 3H-ACh synthesis was seen in group 1. A comparison between group 2+ and group 2- indicated that induced convulsions were not critical for this effect. In the striatum there was a significant reduction in the total uptake of radioactivity in group 1 and group 2- when values were compared to the control group. Furthermore a significant positive correlation was found between the concentration of radiolabel and 3H-ACh synthesis and a negative relationship with the level of 3H-Ch. In the midbrain preparation the synthesis of 3H-ACh was reduced in group 1 where a significant negative correlation was found between the average threshold dose of choline and both 3H-ACh and 3H-PhCh synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353355 TI - Effects of treatment with phenobarbitone or isoniazid on hepatotoxicity due to prolonged subanaesthetic halothane inhalation. AB - Rats were exposed to halothane vapour, 50 p.p.m., or air for a period of four weeks. Within each exposure group, some animals drank plain water, some received water plus phenobarbitone, while some received water plus isoniazid. Halothane exposure resulted in increased serum bromide concentrations and liver injury evidenced by increased serum alanine aminotransferase activity, focal hepatocellular necrosis and fatty change. Administration of isoniazid reduced halothane metabolism by 33% as assessed by serum bromide concentrations, and completely blocked the injurious effects of halothane on the liver, suggesting that halothane metabolism plays a role in halothane hepatotoxicity under these conditions. Administration of phenobarbitone partially prevented the increase in serum alanine aminotransferase activity and hepatocellular necrosis due to halothane. In contrast to isoniazid, phenobarbitone led to a slight increase in halothane metabolism. However, phenobarbitone also caused an increase in liver size, such that the amount of halothane metabolised per gram of liver was reduced by phenobarbitone treatment. These results suggest that metabolism of halothane is an important factor in liver injury due to prolonged, subanaesthetic halothane exposure. PMID- 3353356 TI - Seasonal variations in serum aluminum concentrations. AB - During 1984 and 1985 we performed frequent measurements of serum aluminum (Al) in patients with moderate chronic renal failure, and healthy controls, all living in the Oslo region. The results demonstrated seasonal variations with high levels in the autumn. During the peak periods serum Al increased by a factor greater than four. Outside the peaks patients using Al-containing phosphate binders had higher serum Al levels than non-users, a difference not seen during the peaks. Serum Al levels were unrelated to parathyroid hormone (PTH) concentrations and to calcitriol intake. Urinary excretion and the glomerular filtration rate was stable during the period with high serum Al in the autumn 1984. Increased gastrointestinal absorption of Al, possibly caused by a waterborne factor with chelating properties, may explain the seasonal variations. PMID- 3353357 TI - Effects of antiparkinsonian drugs on muscarinic receptor binding in rat brain, heart and lung. AB - The anticholinergic antiparkinsonian drugs biperiden, benztropine, trihexyphenidyl, methixene, and procyclidine were compared with atropine and pirenzepine, as well as with orphenadrine, amantadine and some standard antidepressives and neuroleptics in their ability to inhibit the binding of tritiated quinuclidinyl benzilate (QNB) to the muscarinic receptors in rat brain cortical tissue. Most of the antiparkinsonian drugs studied were potent inhibitors of (-)3H-QNB binding, when compared to atropine (IC50-value = 0.22 microM), the IC50-values ranging from 0.0084 microM (biperiden) to 0.07 microM (procyclidine). Orphenadrine had a low and amantadine no evident affinity for muscarinic receptors. With the exception of pirenzepine and biperiden the inhibition curves were steep and parallel, giving linear Hill plots with coefficients close to unity. The binding profile of atropine, pirenzepine, and biperiden was further studied in heart and lung tissues, atropine showing only small divergences in its binding to the different tissues, but biperiden and pirenzepine having five to ten times lower affinity in the peripheral tissues than in the brain. The results confirm the high affinity of most of the antiparkinsonian drugs for brain muscarinic receptors. The dissociation constants agree with the average clinical doses of the drugs. It must be remembered, however, that the binding data may represent multiple events at receptor sites because most of the drugs used are mixtures of stereoisomers. Thus further studies using individual enantiomers are needed to compare more directly binding data between the compounds. PMID- 3353358 TI - Tissue distribution of 125I-labelled bovine superoxide dismutase (SOD) in the rat. AB - Bovine copper/zinc superoxide dismutase (SOD) was labelled with 125I using the chloramine-T method. The tissue distribution of 125I-SOD (dose of SOD 5 mg/kg) was studied with whole-body and microautoradiography at various times after an intravenous injection. The distribution of 125I-SOD showed a remarkable organ specificity in that the localization of the enzyme to the kidneys and the urinary tract completely dominated the autoradiograms. The time pattern of localization of 125I-SOD also gives a clear picture of the renal handling of the enzyme in that, as a consequence of the renal elimination, the enzyme rapidly disappears from the circulation with an elimination half time of about 6 min. Up to 20 min. after the injection, there were high concentrations of 125I-SOD in the renal pelvis, ureter and urinary bladder showing that in addition to renal uptake there was an initial substantial urinary excretion of the enzyme. From the microautoradiography it is clear that the grains were exclusively localized over proximal tubular cells and tended to be concentrated at the luminal rather than the peritubular side of tubule. This would be compatible with renal uptake secondary to glomerular filtration of 125I-SOD, which is what one would expect from the renal handling of a protein with a molecular weight around 31,000 and an isoelectric point around pH 5.4. Pretreatment with a large dose of SOD (88 mg/kg) tended to competitively decrease the renal uptake of labelled SOD after 5 min. and apparently further increase its renal excretion. However, a noticeable renal uptake of 125I-SOD was still apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353359 TI - [The German Central Committee for the Control of Tuberculosis. Guidelines for tuberculin diagnosis (tuberculin test)]. PMID- 3353360 TI - [Primary tracheobronchial amyloidosis--endobronchial laser treatment with the neodymium-Yag laser]. PMID- 3353361 TI - [New developments in the diagnosis of occupational asthma]. PMID- 3353363 TI - [Interaction pattern and therapy of compulsive families]. PMID- 3353362 TI - [Comprehensive determination of laterality at a speech pathology clinic]. PMID- 3353364 TI - [Evaluation of pediatric and adolescent psychiatric treatment in 3 Hessian districts]. PMID- 3353365 TI - Diffusion in a rough potential. AB - Diffusion in a spatially rough one-dimensional potential is treated by analysis of the mean first passage time. A general expression is found for the effective diffusion coefficient, which can become very small at low temperatures. PMID- 3353366 TI - Proline metabolism in N2-fixing root nodules: energy transfer and regulation of purine synthesis. AB - N2-fixing root nodules of soybean (Glycine max L. Merr.) convert atmospheric N2 to ammonia(um) in an energy-intensive enzymatic reaction. These nodules synthesize large quantities of purines because nitrogen fixed by bacteria contained within this tissue is transferred to the shoots in the form of ureides, which are degradation products of purines. In animal systems, it has been proposed that proline biosynthesis by pyrroline-5-carboxylate reductase (P5CR) is used to generate the NADP+ required for the synthesis of the purine precursor ribose 5-phosphate. We have examined the levels, properties, and location of P5CR and proline dehydrogenase (ProDH) in soybean nodules. Nodule P5CR was found in the plant cytosol. Its activity was substantially higher than that reported for other animal and plant tissues and is 4-fold higher than in pea (Pisum sativum) nodules (which export amides). The Km for NADPH was lower by a factor of 25 than the Km for NADH, while the Vmax with NADPH was one-third of that with NADH. P5CR activity was diminished by NADP+ but not by proline. These characteristics are consistent with a role for P5CR in supporting nodule purine biosynthesis rather than in producing proline for incorporation into protein. ProDH activity was divided between the bacteroids and plant cytosol, but less than 2% was in the mitochondria-rich fractions. The specific activity of ProDH in soybean nodule bacteroids was comparable to that in rat liver mitochondria. In addition, we propose that some of the proline synthesized in the plant cytosol by P5CR is catabolized within the bacteroids by ProDH and that this represents a novel mechanism for transferring energy from the plant to its endosymbiont. PMID- 3353367 TI - Nonsense mutations in the human beta-globin gene affect mRNA metabolism. AB - A number of premature translation termination mutations (nonsense mutations) have been described in the human alpha- and beta-globin genes. Studies on mRNA isolated from patients with beta zero-thalassemia have shown that for both the beta-17 and the beta-39 mutations less than normal levels of beta-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human beta-globin mRNA.) In vitro studies using the cloned beta-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. We have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, we have studied the effect of five nonsense mutations and two missense mutations on the expression of human beta-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation. PMID- 3353368 TI - Continuous synthesis of two protein-kinase-C-related proteins after down regulation by phorbol esters. AB - The phorbol 12-myristate 13-acetate (PMA)-dependent down-regulation of immunoprecipitable protein kinase C was studied in human breast cancer cell lines that display different growth inhibitions toward the tumor promoter. PMA induces translocation of [35S]methionine-prelabeled cytosolic protein kinase C to membranes, followed by complete degradation of the enzyme (t1/2, 2 hr). PMA does not affect the protein kinase C synthesis; 20-80% of total protein kinase C of control cells was still immunoprecipitable as membrane-bound 74- and 80-kDa protein kinase C-related polypeptides if cells were allowed to incorporate [35S]methionine during PMA exposure for greater than 6 hr. These two proteins lack protein kinase activity and phorbol ester binding but reveal V8 peptide patterns identical to the active forms of protein kinase C (77/80 kDa) of PMA untreated cells. The amounts of the immunoprecipitable membrane-bound 80-kDa protein kinase C-related polypeptide synthesized during the prolonged PMA treatment appear to inversely correlate with the extent of PMA-mediated growth inhibition of the respective human breast cancer cell line. These data suggest that after homologous down-regulation, functional protein kinase C (77/80 kDa) is replaced by a population of membrane-associated but enzymatically inactive protein kinase C-related polypeptides (74/80 kDa). PMID- 3353369 TI - Splicing mutation in human hereditary analbuminemia. AB - We have identified a structural defect in the serum albumin gene in human analbuminemia. Sequence determination of 1.1 kilobases (kb) of the 5' regulatory region and of 6 kb across exonic regions revealed a single AG-to-GG mutation within the 3' splice site of intron 6 in the defective gene of an analbuminemic individual. In an in vitro assay on the RNA transcript this mutation causes a defect in splicing of the intron 6 sequence and in subsequent ligation of the exon 6-exon 7 sequences. Using polymerase-amplified genomic DNA and allele specific oligodeoxynucleotide probes, we have also shown that the sequence of this intron 6/exon 7 splice junction is normal in a different, unrelated analbuminemic individual. Analbuminemia in humans is therefore the result of one of multiple defects in our genome. PMID- 3353371 TI - Neural networks counting chimes. AB - It is shown that the ideas that led to neural networks capable of recalling associatively and asynchronously temporal sequences of patterns can be extended to produce a neural network that automatically counts the cardinal number in a sequence of identical external stimuli. The network is explicitly constructed, analyzed, and simulated. Such a network may account for the cognitive effect of the automatic counting of chimes to tell the hour. A more general implication is that different electrophysiological responses to identical stimuli, at certain stages of cortical processing, do not necessarily imply synaptic modification, a la Hebb. Such differences may arise from the fact that consecutive identical inputs find the network in different stages of an active temporal sequence of cognitive states. These types of networks are then situated within a program for the study of cognition, which assigns the detection of meaning as the primary role of attractor neural networks rather than computation, in contrast to the parallel distributed processing attitude to the connectionist project. This interpretation is free of homunculus, as well as from the criticism raised against the cognitive model of symbol manipulation. Computation is then identified as the syntax of temporal sequences of quasi-attractors. PMID- 3353370 TI - The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence. AB - The primary structure of the beta chain of human glycoprotein Ib (GPIb), the platelet receptor for von Willebrand factor, has been established by a combination of cDNA cloning and amino acid sequence analysis. A lambda phage cDNA expression library prepared from human erythroleukemia cells (HEL cells) was screened with a radiolabeled affinity-purified rabbit polyclonal antibody to the beta chain of GPIb. Eighteen positive clones were isolated and plaque-purified and the nucleotide sequences of three were determined. The composite sequence spanned 968 nucleotides and included a 5' untranslated region of 22 nucleotides, an open reading frame of 618 nucleotides encoding a signal peptide of 28 amino acids and a mature protein of 181 amino acids, a stop codon, and a 3' noncoding region of 307 nucleotides. The 3' noncoding sequence also contained a polyadenylylation signal (AATAAA) 14 nucleotides upstream from the poly(A) tail of 18 nucleotides. Edman degradation of the intact beta chain and of peptides produced by chemical cleavage yielded amino acid sequences spanning 76 residues that were identical to those predicted from the cDNA. The amino-terminal region of the beta chain contains a leucine-rich sequence of 24 amino acids that is similar to a sequence that occurs as seven tandem repeats in the alpha chain of GPIb and nine tandem repeats in leucine-rich alpha 2-glycoprotein. The leucine rich sequence in the beta chain of GPIb is flanked on both sides by amino acid sequences that are similar to those flanking the leucine-rich tandem repeats of the alpha chain of GPIb and leucine-rich alpha 2-glycoprotein. The amino-terminal region of the beta chain of GPIb is followed by a transmembrane segment of 25 amino acids and an intracellular segment of 34 amino acids at the carboxyl terminus of the protein. The intracellular segment contains an unpaired cysteine and two potential sites for phosphorylation by cAMP-dependent protein kinase. PMID- 3353372 TI - The effect of quaternary structure on the kinetics of conformational changes and nanosecond geminate rebinding of carbon monoxide to hemoglobin. AB - To determine the effect of quaternary structure on the individual kinetic steps in the binding of carbon monoxide to the alpha subunit of hemoglobin, time resolved absorption spectra were measured after photodissociation of carbon monoxide from a hemoglobin tetramer in which cobalt was substituted for iron in the beta subunits. Cobalt porphyrins do not bind carbon monoxide. Spectra were measured in the Soret region at room temperature after time delays that varied from a few nanoseconds to the completion of ligand rebinding at about 100 ms. The results show that the liganded molecule, alpha(Fe-CO)2 beta(Co)2, is in the R state, but can be almost completely switched into the T state by the allosteric effectors inositol hexaphosphate and bezafibrate. The geminate yield, which is the probability that the ligand rebinds to the heme from within the protein, is found to be 40% for the R state and less than 1% for the T state. According to the simplest kinetic model, these results indicate that carbon monoxide enters the protein in the R and T quaternary conformations at the same rate, and that the 60-fold decrease in the overall binding rate, of carbon monoxide to the alpha subunit in the T state compared to the R state is almost completely accounted for by the decreased probability of binding after the ligand has entered the protein. The results further suggest that the low probability for the T state results from a decreased binding rate to the heme and not from an increased rate of return of the ligand to the solvent. PMID- 3353373 TI - Bacteriorhodopsin's L550 intermediate contains a C14-C15 s-trans-retinal chromophore. AB - Conformational changes of the retinal chromophore about the C14-C15 bond in bacteriorhodopsin (BR) have been proposed in models for the mechanism of light driven proton transport. To determine the C14-C15 conformation in BR's L550 intermediate, we have examined the resonance Raman spectra of BR derivatives regenerated with retinal deuterated at the 14 and 15 positions. Vibrational calculations show that the C14-2H and C15-2H rocking modes form symmetric (A) and antisymmetric (B) combinations in [14,15-2H]retinal chromophores. When there is a trans conformation about the single bond between C14 and C15 (14-s-trans), a small frequency separation or splitting is observed between the A and B modes, which are found at approximately equal to 970 cm-1. In 14-s-cis molecules, the splitting is large, and the Raman-active symmetric A mode is predicted at approximately equal to 850 cm-1. In addition, the monodeuterium rock should appear at an unusually low frequency (920-930 cm-1) in the 14-2H-labeled 14-s-cis molecules. These patterns are insensitive to computational details: similar results are predicted by a modified Urey-Bradley force field and by MNDO (modified neglect of differential overlap) calculations for twisted chromophores and for highly delocalized protonated Schiff base cations. Time-resolved resonance Raman spectra were obtained of BR's L550 intermediate regenerated with [14-2H]-, [15-2H]- and [14,15-2H]retinal. The symmetric A rock in L550 is found at 968 cm-1, within 4 cm-1 of the frequencies for the monodeuterio derivatives, and no scattering is observed between 800 and 940 cm-1. The rocking frequencies of deuterated L550 are within 5 cm-1 of those observed in BR568, which contains a 14-s-trans chromophore. These results show that L550 contains a 14-s-trans chromophore and suggest that only 14-s-trans structures are involved in the proton pumping photocycle of BR. PMID- 3353374 TI - Cell-cell and cell-matrix interactions differentially regulate the expression of hepatic and cytoskeletal genes in primary cultures of rat hepatocytes. AB - Freshly isolated adult rat hepatocytes exhibit a flat, extended morphology when cultured on dried rat tail collagen in the presence of growth factors; they actively synthesize DNA and express high levels of cytoskeletal mRNAs and proteins (actin, tubulin, cytokeratins, vinculin, alpha-actinin, and desmoplakin), while exhibiting low levels of liver-specific mRNAs (albumin, alpha 1-inhibitor III, and alpha 1-antitrypsin) and limited synthesis and secretion of albumin. Hepatocytes cultured on hydrated gel matrix from the Engelbreth-Holm Swarm (EHS) mouse tumor form small spherical aggregates and exhibit low DNA, cytoskeletal mRNA, and protein synthesis, while at the same time exhibiting elevated liver-specific mRNAs and albumin production; these cells, therefore, more nearly conform to the program of gene expression seen within the normal animal. Hepatocytes on hydrated rat tail collagen resemble those on dry collagen when cultured at low density, but at high density they form compact trabecular aggregates, synthesize negligible amounts of DNA, and maintain a pattern of gene expression resembling that of hepatocytes seeded on the EHS matrix. If cell morphology is compact, as on EHS or on hydrated rat tail collagen when densely populated, DNA synthesis and expression of cytoskeletal genes are low, while liver-specific mRNAs are abundant. When cells are extended the opposite is the case. Without the growth supplement DNA synthesis is low throughout but gene expression is little affected. These studies point to the importance of cell-cell and cell-matrix interactions in determining the differentiated phenotype of hepatocytes, and they reveal an inverse relationship between cytoskeletal and liver-specific protein expression. PMID- 3353375 TI - Mouse ornithine decarboxylase gene: cloning, structure, and expression. AB - We used molecular cloning to isolate a functional gene for mouse ornithine decarboxylase (OrnDCase; L-ornithine carboxy-lyase, EC 4.1.1.17) from a cell line in which that gene had been selectively amplified. The position of the 5' terminus of the mRNA was identified, and the coding sequence was shown to be preceded by a 312- or 313-nucleotide (nt) untranslated leader. The latter is highly G + C rich, particularly in its 5'-most portion. The leader can be anticipated to have extensive and stable secondary structure. The transcription unit of the gene is of relatively small size, approximately equal to 6.2 kilobases (kb) from the start site to the proximal site of polyadenylylation. Sequence analysis of DNA near the transcription start position demonstrated the presence of a "TATA" box, but no "CAAT" box. Functional properties of the cloned gene were tested by transfecting it into cultured cells. Expression of the putative full-length gene efficiently conferred ornithine decarboxylase activity on recipient mutant cells deficient in that activity. To assess the function and strength of the OrnDCase promoter region and to delimit its boundaries, we used a transient expression assay. Upstream of a bacterial chloramphenicol acetyltransferase gene was placed a portion of the OrnDCase gene, including the presumed promoter region, spanning a region from approximately equal to 3.0 kb 5' of the site of transcription initiation to the first 250 nt of the transcript. When expressed in mouse NIH 3T3 cells, this OrnDCase genomic element was comparable in strength to the Rous sarcoma virus long terminal repeat promoter. A similar construct, truncated so as to retain only 264 base pairs of the OrnDCase gene 5' to the site of transcription start, yielded undiminished levels of expression. PMID- 3353377 TI - Lamin B is rapidly phosphorylated in lymphocytes after activation of protein kinase C. AB - Lamin B was shown to be a major substrate of cellular phosphorylation in the response of lymphocytes to phorbol esters. Lamins A and C, which were not observed in lymphocytes, were also substrates of phorbol-stimulated phosphorylation in those cell types that express them. Lamin B phosphopeptides labeled with 32P in intact cells treated with phorbol 12-myristate 13-acetate were compared to those produced by in vitro phosphorylation with protein kinase M, cAMP-dependent protein kinase, and Ca2+/calmodulin-dependent protein kinase II. The phosphopeptides labeled by in vivo stimulation with phorbol esters are very similar to those phosphorylated in vitro by protein kinase M, a catalytic domain of protein kinase C. Phorbol treatment of interphase cells significantly reduces the amount of detergent-insoluble lamin B, suggesting that phosphorylation of lamin may alter the architecture of the nuclear lamina. In addition, we have shown that treatment of a B-cell line with antibodies to IgM induces a modest increase in lamin B phosphorylation. These results strongly suggest that ligands that are known to activate protein kinase C at the cell surface or in the cytosol also lead to the activation of a nuclear kinase activity with a protein kinase C-type specificity. PMID- 3353376 TI - Cell-cycle regulation as a mechanism for targeting proteins to specific DNA sequences in Tetrahymena thermophila. AB - Transcriptionally active macronuclei and transcriptionally inert micronuclei of the ciliated protozoan Tetrahymena thermophila contain similar DNA sequences but have very different histones associated with the linker regions of chromatin. In situ hybridization showed that a gene coding for micronuclear linker histone is expressed only in association with micronuclear DNA replication, whereas the gene for macronuclear H1 histone is expressed during macronuclear (but not during micronuclear) S phase. These results indicate that cell-cycle regulation plays an important role in directing proteins to the appropriate nucleus in Tetrahymena and that the replication-expression model [Gottesfeld, J. & Bloomer, L. S. (1982) Cell 28, 781-791; Wormington, W. M., Schlissel, M. & Brown, D. D. (1983) Cold Spring Harbor Symp. Quant. Biol. 47, 879-884] for establishing appropriate transcriptionally active or repressed chromatin complexes during DNA replication is generally applicable. PMID- 3353378 TI - Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells. AB - The predominant subclasses of mast cells in both the rat and the mouse can be distinguished from one another by their preferential synthesis of 35S-labeled proteoglycans that contain either heparin or oversulfated chondroitin sulfate glycosaminoglycans. Although [35S]heparin proteoglycans have been isolated from human lung mast cells of 40-70% purity and from a skin biopsy specimen of a patient with urticaria pigmentosa, no highly sulfated chondroitin sulfate proteoglycan has been isolated from any enriched or highly purified population of human mast cells. We here demonstrate that human lung mast cells of 96% purity incorporate [35S] sulfate into separate heparin and chondroitin sulfate proteoglycans in an approximately equal to 2:1 ratio. As assessed by HPLC of the chondroitinase ABC digests, the chondroitin [35S]sulfate proteoglycans isolated from these human lung mast cells contain the same unusual chondroitin sulfate E disaccharide that is present in proteoglycans produced by interleukin 3-dependent mucosal-like mouse mast cells. Both the chondroitin [35S]sulfate E proteoglycans and the [35S]heparin proteoglycans were exocytosed from the [35S]sulfate-labeled cells via perturbation of the IgE receptor, indicating that both types of 35S labeled proteoglycans reside in the secretory granules of these human lung mast cells. PMID- 3353379 TI - Enhanced osteoblast proliferation and collagen gene expression by estradiol. AB - Estrogens play a crucial role in the development of postmenopausal osteoporosis. However, the mechanism by which estrogens exert their effects on bone is unknown. To examine possible direct effects of 17 beta-estradiol on bone-forming cells, we used pure rat osteoblast-like cells in vitro as a model. Osteoblast-like cells prepared from calvaria of newborn rats were cultured serum-free in methylcellulose-containing medium for 21 days. Osteoblast-like cells proliferate selectively into clonally derived cell clusters of spherical morphology. 17 beta Estradiol at concentrations of 0.1 nM and 1 nM enhanced osteoblast-like cell proliferation by 41% and 68% above vehicle-treated controls. The biologically inactive stereoisomer 17 alpha-estradiol (same concentrations) had no effect. Moreover, the antiestrogen tamoxifen abolished the stimulation of osteoblast-like cell proliferation by 17 beta-estradiol. After 21 days of culture, RNA was prepared and analyzed in a dot-hybridization assay for the abundance of pro alpha 1(I) collagen mRNA. Steady-state mRNA levels were increased in cultures treated with 17 beta-estradiol in a dose-dependent manner with maximal stimulation at 1 nM and 10 nM. At the same concentrations, the percentage of synthesized protein (labeled by [3H]proline pulse) that was digestible by collagenase was increased, indicating that 17 beta-estradiol acts at pretranslational levels to enhance synthesis of bone collagen. These data show that the osteoblast is a direct target for 17 beta-estradiol. PMID- 3353380 TI - Thiazide diuretic drug receptors in rat kidney: identification with [3H]metolazone. AB - Thiazides and related diuretics inhibit NaCl reabsorption in the distal tubule through an unknown mechanism. We report here that [3H]metolazone, a diuretic with a thiazide-like mechanism of action, labels a site in rat kidney membranes that has characteristics of the thiazide-sensitive ion transporter. [3H]Metolazone bound with high affinity (Kd = 4.27 nM) to a site with a density of 0.717 pmol/mg of protein in kidney membranes. The binding site was localized to the renal cortex, with little or no binding in other kidney regions and 11 other tissues. The affinities of thiazide-type diuretics for this binding site were significantly correlated with their clinical potency. Halide anions (Cl-, Br-, and I-) specifically inhibited high-affinity binding of [3H]metolazone to this site. [3H]Metolazone also bound with lower affinity (Kd = 289 nM) to sites present in kidney as well as in liver, testis, lung, brain, heart, and other tissues. Calcium antagonists and certain smooth muscle relaxants had Ki values of 0.6-10 microM for these low-affinity sites, which were not inhibited by most of the thiazide diuretics tested. Properties of the high-affinity [3H]metolazone binding site are consistent with its identity as the receptor for thiazide-type diuretics. PMID- 3353381 TI - Immunological lesions in human uracil DNA glycosylase: association with Bloom syndrome. AB - Three monoclonal antibodies that react with uracil DNA glycosylase of normal human placenta were tested to determine whether one of the antibodies could be used as a negative marker for Bloom syndrome. As defined by enzyme-linked immunosorbent assay, monoclonal antibody 40.10.09, which reacts with normal human glycosylase, neither recognized nor inhibited native uracil DNA glycosylase from any of five separate Bloom syndrome cell strains. Immunoblot analyses demonstrated that the denatured glycosylase protein from all five Bloom syndrome cell strains was immunoreactive with the 40.10.09 antibody. Further, each native enzyme was immunoreactive with two other anti-human placental uracil DNA glycosylase monoclonal antibodies. In contrast, ELISA reactivity was observed with all three monoclonal antibodies in reactions of glycosylases from 5 normal human cell types and 13 abnormal human cell strains. These results experimentally verify the specificity of the aberrant reactivity of the Bloom syndrome uracil DNA glycosylase. The possibility arises that determination of the lack of immunoreactivity with antibody 40.10.09 may have value in the early diagnosis of Bloom syndrome. PMID- 3353382 TI - Cholesteryl ester accumulation in macrophages incubated with low density lipoprotein pretreated with cigarette smoke extract. AB - Although cigarette smoking is one of the major risk factors for atherosclerosis and coronary heart disease, the precise mechanisms of its adverse effects have not been fully elucidated. We incubated low density lipoprotein (LDL) with cigarette smoke (CS) extract and examined the incorporation of the lipoprotein by macrophages in vitro. When incubated with macrophages, LDL pretreated with CS extract (100 micrograms/ml) stimulated cholesteryl [14C]oleate synthesis approximately equal to 12.5-fold that with unmodified LDL and transformed macrophages to cells rich in lipid droplets positively stained with oil red O. Enhancement in cholesteryl ester synthesis was dependent on the concentration of CS-modified LDL and exhibited saturation kinetics. When subjected to electrophoreses, CS-modified LDL migrated to a more anionic position than did unmodified LDL and showed extensive fragmentation of apolipoprotein B. This LDL modification depended upon the incubation time and concentration of the CS extract. Superoxide dismutase inhibited modification of LDL by 52%, suggesting that superoxide anion is, at least in part, involved. These results suggest that CS extract alters LDL into a form recognized and incorporated by macrophages. Such modification if it occurs in vivo, could explain the increased incidence of atherosclerosis and coronary heart disease in smokers. PMID- 3353384 TI - Evidence that associative interactions between synapses during the induction of long-term potentiation occur within local dendritic domains. AB - The present study evaluates whether the associative interactions between synapses that lead to long-term potentiation and depression (LTP and LTD) can occur between spatially segregated synapses of the medial and lateral temporodentate pathway of the rat. Coconditioning of crossed and ipsilateral pathways resulted in LTP of the crossed system only when the current sinks of the two conditioned pathways overlapped sufficiently. Likewise, conditioning of an ipsilateral pathway alone resulted in LTD of the crossed pathway only when those current sinks overlapped sufficiently. These observations support the idea that associative events that lead to LTP or LTD can be restricted to a local dendritic domain. The postsynaptic cell can therefore serve as more than one unit of integration for synaptic modification. PMID- 3353383 TI - Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals. AB - Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in the type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is approximately equal to 80% informative in all Gaucher patients studied. PMID- 3353385 TI - Long-term memory in Aplysia modulates the total number of varicosities of single identified sensory neurons. AB - The morphological consequences of long-term habituation and sensitization of the gill withdrawal reflex in Aplysia california were explored by examining the total number of presynaptic varicosities of single identified sensory neurons (a critical site of plasticity for the biochemical and biophysical changes that underlie both types of learning) in control and behaviorally trained animals. Sensory neurons from habituated animals had 35% fewer synaptic varicosities than did sensory neurons from control animals. In contrast, sensory neurons from sensitized animals had twice as many varicosities per sensory neuron compared to controls, as well as enlarged neuropil arbors. These changes suggest that modulation of synapse number may play a role in the maintenance of long-term memory. PMID- 3353386 TI - Purification and reconstitution of serotonin receptors from bovine brain. AB - An affinity-chromatography column was used to isolate and purify 5 hydroxytryptamine (serotonin, 5-HT) receptors from bovine brain frontal cortex. The affinity ligand lysergic acid ethylamidoethylbromide was synthesized and coupled to an agarose matrix via a thioether bond. Receptors in the crude cortical membrane fragments were solubilized using 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS), affinity purified, and reconstituted into lipid vesicles. [3H]5-HT binding analysis indicates a single class of high affinity binding site (Kd, 16.9 nM) that was reconstituted. 5-Methoxytryptamine, a competitor for high-affinity serotonin sites, inhibited this binding and showed a Ki of 27.4 nM. Ketanserin, a high-affinity ligand for 5-HT2 type receptors, was ineffective in displacing [3H]5-HT binding at concentrations up to 4 microM indicating a 5-HT1 receptor as the primary receptor type isolated. The average specific activity of 359 pmol/mg in the reconstituted fractions is an enrichment of 1062-fold over crude membrane fragments. Sodium dodecyl-sulfate electrophoresis showed the presence of four proteins in the reconstituted vesicles with approximate relative Mr values of 63,000, 70,000, 81,000, and 94,000. PMID- 3353388 TI - Acidic fibroblast growth factor enhances regeneration of processes by postnatal mammalian retinal ganglion cells in culture. AB - Postnatal rat retinal ganglion cells (RGCs) were identified with specific fluorescent labels and placed in culture. Under these conditions, the outgrowth of processes by RGCs was found to be promoted to a far greater degree by acidic fibroblast growth factor (aFGF) than by basic fibroblast growth factor (bFGF). The effect of aFGF and bFGF on process extension by solitary RGCs was quantified after 24 hr in culture, a time when neither a FGF nor bFGF enhanced RGC survival. The action of aFGF on process outgrowth was markedly potentiated by the addition of heparin (10 micrograms/ml) to the medium, but heparin alone had no effect. In the presence of heparin, half-maximal process outgrowth occurred at an aFGF concentration of less than 20 pg/ml (1 pM). Since all of the centrally projecting processes have already been formed in the living animal prior to use (at 7-12 days of age), at least a portion of the process outgrowth in culture appears to represent a regenerative phenomenon. Statistical analysis of the increase in process growth revealed that aFGF with heparin contributed to both neurite initiation and elongation. The mean number of glial cells, identified with polyclonal antiserum against glial fibrillary acidic protein, was slightly increased in cultures receiving aFGF plus heparin, but this effect was variable, and these glial cells were not in contact with the solitary RGCs that were scored for regeneration of processes. Thus, glial cells probably did not exert a direct physical influence on the degree of process outgrowth observed in the solitary RGCs, although a humoral effect cannot be totally excluded. These results suggest that aFGF has a potent influence on the outgrowth of processes by a neuron in the mammalian central nervous system. The potentiation of this effect by heparin leads us to speculate that the interaction of aFGF with a heparin-like molecule located in the extracellular matrix (such as heparan sulfate proteoglycan) may produce physiological effects in vivo. Furthermore, the lack of a substantial effect of bFGF in this system under these conditions shows that a specific population of mammalian central neurons may be differentially influenced by these two closely related peptide growth factors. PMID- 3353387 TI - Odorant-binding protein and its mRNA are localized to lateral nasal gland implying a carrier function. AB - Odorant-binding protein selectively binds various odorants and is discretely concentrated in nasal mucosa and secretions. We have localized rat odorant binding protein mRNA to the lateral nasal gland by in situ hybridization histochemistry and have also localized the protein to this gland by immunohistochemistry and by tritiated-odorant autoradiography. The lateral nasal gland extends a long duct toward the external nares. Odorant-binding protein, released from this duct, may transport odorants to olfactory receptor neurons. PMID- 3353390 TI - Influence of serotonin on myocardial blood flow in the presence and absence of a coronary arterial stenosis: observations in domestic swine. AB - This study tested the hypothesis that 5-HT may impair coronary flow regulation by inappropriately increasing arteriolar tone in the coronary circulation. Ten closed chest, domestic swine were studied both in the presence and in the absence of a severe artificial intraluminal coronary stenosis. A 5-French micromanometer catheter with fluid lumen was placed in the left anterior descending coronary artery and used to record pressure and infuse 5-HT (40 and 100 micrograms/min) into the coronary circulation. For the stenosis phase of the protocol the catheter was embedded in the artificial stenosis. Hemodynamics, regional myocardial blood flow (microsphere technique), coronary vascular resistance, lactate consumption, and oxygen metabolism were measured at control and at 5 min of each 5-HT dose. In the absence of coronary artery stenosis (i.e., full vasodilatory reserve), there was no change in regional myocardial blood flow or coronary vascular resistance during 5-HT infusion. In the presence of a severe coronary stenosis (i.e., limited vasodilator reserve) 5-HT produced a significant (P less than 0.05) decrease versus control in the distal left anterior descending: circumflex zone endocardial blood flow ratio (0.63 +/- 0.19, mean +/- 1 SD, to 0.55 +/- 0.15) and a significant (P less than 0.05) increase versus control in endocardial (50.6 +/- 16.6 to 61.2 +/- 19.8 mm Hg/ml/min/g) and transmural (49.9 +/- 9.5 to 57.2 +/- 12.8) coronary vascular resistance. Thus, 5 HT does not impair coronary flow regulation when full vasodilatory reserve is present. When coronary vasodilatory reserve is impaired by the presence of a severe proximal stenosis, 5-HT causes modest impairment of endocardial flow regulation. PMID- 3353389 TI - Desensitization of rat renal thick ascending limb cells to vasopressin. AB - Previous studies from this laboratory have demonstrated that vasopressin stimulates K, Mg, Ca, Cl, and Na reabsorption by the thick ascending limb of Henle's loop (TALH) of the rat kidney. Micropuncture of superficial nephrons and clearance experiments were performed to determine whether desensitization of the TALH to vasopressin may be demonstrated in vivo and whether such desensitization is specific for the effects of vasopressin (i.e., homologous) or also alters the response to the other hormones acting on the same pool of adenylate cyclase in this nephron segment. Brattleboro rats, with hereditary hypothalamic diabetes insipidus (DI), were given i.m. injections of 1-desamino-8-D-arginine-vasopressin (des-1-amino-[DArg8]VP (herein designated dDAVP); 2 micrograms/day) for 3 days. The effects of maximal physiological doses of arginine-8-vasopressin ([Arg8]VP (herein designated AVP); 20 pg/min per 100 g of body weight) were studied 2 days after the cessation of treatment, when the animals had returned to DI. The K, Mg, Ca, and, to a lesser extent, Cl and Na concentrations in the fluid leaving the TALH of superficial nephrons were higher in dDAVP-treated than in untreated rats given similar amounts of AVP during the experiments. A 50-60% desensitization of the TALH to AVP was still apparent 2 days after stopping the dDAVP injections. Desensitization is homologous, as judged from normal responses to physiological doses of glucagon and calcitonin, two hormones acting on the same cyclase pool as AVP in the rat TALH. The AVP-dependent increase of urine osmolality, however, indicated that its effects on the permeability to water of the collecting duct were scarcely affected in dDAVP-treated rats. It is concluded that (i) AVP induces homologous desensitization in the rat TALH and (ii) the TALH can be markedly desensitized to AVP when the collecting duct response to this hormone is poorly affected or even fully maintained. PMID- 3353392 TI - Effect of topically applied beta-aminopropionitrile on granuloma tissue biochemistry. AB - The effects of the percutaneous transport of vehicles and the transport of beta amino-propionitrile (beta APN) in vehicles were studied in rats. The bioavailability of topically administered beta APN was determined by measuring the degree of collagen cross-linking inhibition in the underlying granuloma tissue. Granulomas were induced by subcutaneous implantation of polyvinylalcohol sponges. From the 4th to 12th days postimplantation, a 20 mg/cm2 dose of beta APN fumarate was applied. Vehicles employed included dimethylsulfoxide (DMSO), urea, and occlusion. DMSO significantly enhanced the effect of beta APN in reducing the cross-linking of collagen. beta APN administered onto urea-pretreated skin and followed by occlusion in the granuloma tissue was more effective than beta APN in 30% DMSO, but only in the parameter reflecting extractibility of collagen into urea or thiocyanate solutions. The results suggest that beta APN administered topically in an appropriate vehicle penetrates the granuloma tissue and affects collagen polymerization. Though beta APN was topically administered, a systemic effect from the drug was evident, as documented by lower body weight of treated rats. PMID- 3353391 TI - Effects of mezerein and diglycerides on ornithine decarboxylase activity in mouse mammary gland explants. AB - One of the most rapid actions of prolactin in mouse mammary gland explants is the stimulation of ornithine decarboxylase (ODC) activity. Several protein kinase C activators including mezerein, dicaprin, diolein, and 1-oleoyl-2-acetyl-rac glycerol were found to stimulate ODC activity as does prolactin. Both mezerein and the diglycerides produced nonadditive responses when tested with maximum stimulatory concentrations of prolactin. The results of these studies therefore provide further evidence that the prolactin stimulation of ODC activation in the mammary gland may involve an activation of protein kinase C. PMID- 3353393 TI - Stimulation of prolactin secretion from turkey anterior pituitary cells in culture. AB - Prolactin (PRL) secretion by monolayer cultures of turkey anterior pituitary cells was significantly increased (up to 44-fold) by vasoactive intestinal peptide (VIP), arginine vasotocin (AVT), and by an extract of turkey hypothalami (HE). Several other neuropeptides (including thyrotropin-releasing hormone) and neurotransmitters were ineffective in influencing PRL secretion at doses up to 10(-6) M. The dynamic PRL response to HE and VIP was studied using superfused pituitary cells attached to microcarrier beads. HE, administered in 30-min pulses, resulted in a significant, dose-related increase in PRL secretion from a basal secretion rate of 2.32 ng/min/10(7) cells to a peak secretion rate of 127.13 ng/min/10(7) cells at the highest dose of HE tested (1 mg tissue equivalent weight/ml). VIP significantly increased PRL secretion at all doses studied (from 10(-10) to 10(-6) M), with 10(-8) M VIP producing a response similar to that observed with 1 mg/ml HE. A highly significant (P less than 0.001) linear relationship was demonstrated between the log-dose of VIP administered and peak PRL secretion rate. These studies suggest that VIP, but not TRH, may be a physiological stimulus for PRL release in the turkey. PMID- 3353394 TI - Stimulation of prolactin release in turkeys by vasoactive intestinal peptide. AB - Vasoactive intestinal peptide (VIP) is a potent releasor of prolactin in birds. The main purpose of this study was to identify its site of action. Synthetic porcine VIP administered intraatrially to freely moving ovariectomized (OVX) turkeys induced an elevation of circulating PRL within 15 min in a dose-related manner. Removal of hypothalamic control of PRL release by surgical disconnection of the neurohemal regions of the median eminence did not significantly diminish the PRL response to VIP. Intraatrial injection of eledoisin or bradykinin into OVX hens did not influence PRL secretion, indicating that the PRL releasing activity of VIP is probably not attributable to its vasodilatory action. These results support the possibility that VIP is an authentic prolactin releasing factor (PRF) in birds. PMID- 3353395 TI - Regional blood flows by the microsphere method: reproducibility in portal hypertensive rats and influence of a portal vein catheter. AB - To determine the reproducibility of splanchnic blood flow measurements by the microsphere method in rats with portal hypertension and the effects of laparotomy with portal vein cannulation, eight groups of 10 rats were studied. Cardiac output and regional blood flows were measured twice, 10 min apart, in pentobarbital anesthetized or awake, sham-operated or portal vein-ligated rats, with or without portal cannulation. Variability between the two successive measurements was not affected by portal hypertension or portal cannulation, and was not different in the splanchnic territory and in other organs. Laparotomy with portal cannulation had no significant effect in sham-operated rats. In awake portal hypertensive rats, cardiac output (53.9 +/- 3.0 vs 45.8 +/- 2.9 ml.min 1.100 g body wt-1, P less than 0.01) and splanchnic blood flow (12.31 +/- 0.72 vs 9.34 +/- 0.85 ml.min-1.100 g body wt-1, P less than 0.01) were lower in portal vein cannulated rats compared with those of non-cannulated animals. In anesthetized portal hypertensive rats blood flows were unaffected by portal cannulation, but arterial pressure (100.2 +/- 4.3 vs 119.9 +/- 3.4 mm Hg, P less than 0.01) and heart rate (366.5 +/- 10.0 vs 405.5 +/- 7.4 beats.min-1, P less than 0.01) were elevated. Anesthesia also decreased portal pressure (14.8 +/- 0.5 vs 12.0 +/- 0.4 mm Hg, P less than 0.05) in portal hypertensive rats. We conclude that the microsphere method remains reproducible in portal hypertensive rat models. Laparotomy with portal cannulation can alter systemic and splanchnic hemodynamics in portal hypertensive rats; these effects can also be changed during pentobarbital anesthesia. Regional blood flow measurements in portal hypertensive rats should be performed in animals without portal cannulation and preferably in the awake state. PMID- 3353397 TI - Inhibition by 2-deoxy-D-ribose of DNA synthesis and growth in Raji cells. AB - When Raji cells were cultured for 3 days in serum-free medium, addition of 2 deoxy-D-ribose at the start of culture inhibited incorporation of [3H]thymidine and cell division. At deoxyribose concentrations between 1 and 5 mM, viability was 80% or greater after 3 days of culture even though 5 mM deoxyribose inhibited thymidine incorporation 95-99%. Inhibition by deoxyribose could be completely reversed if the culture medium was replaced with fresh medium up to 8 hr after the start of culture. The inhibition was specific for deoxyribose since other monosaccharides had no effect. Inhibition of DNA synthesis did not appear to be due to depletion of essential nutrients in the medium since the percentage inhibition of thymidine incorporation by cells cultured either in suboptimal serum-free media or in media supplemented with 0.025-5% human AB serum was similar. When DNA repair synthesis was measured as hydroxyurea-resistant thymidine incorporation, addition of deoxyribose to Raji cultures caused increased thymidine incorporation. These results, together with data from others, suggest that deoxyribose damages DNA. PMID- 3353396 TI - Effect of high calcium diet on magnesium, catecholamines, and blood pressure of stroke-prone spontaneously hypertensive rats. AB - To test the effect of a high dietary calcium intake on blood pressure, we fed stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto rats (WKY) diets containing (a) 0.25% Ca/0.08% Mg, (b) 4.0% Ca/0.02% Mg, and (c) 4.0% Ca/0.08% mg, beginning at 6 weeks of age. SHR-SP and WKY rats receiving 4% Ca with the lower Mg content had lower blood pressures, hypomagnesemia, and hypomagnesuria, and grew poorly. SHR-SP receiving 4% Ca and the higher Mg diet had blood pressures no different from those of rats receiving the 0.25% Ca diet, in spite of having lower body weights. Rubidium flux studies in erythrocytes were not influenced by Ca or Mg in the diets. Plasma phosphate values were moderately reduced in rats receiving 4% Ca diets. Epinephrine and norepinephrine values were higher in SHR-SP than in WKY rats. Norepinephrine increased with stress in both strains, independent of diet. Epinephrine values were lower in SHR-SP receiving the 4% Ca diets and showed less of an increase with stress compared to SHR-SP receiving the 0.25% Ca diet. After 26 weeks of diets, SHR-SP and WKY rats were given 0.9% NaCl in their drinking water. NaCl increased blood pressure in SHR-SP irrespective of Ca content of the diet. These data suggest that a high Ca diet influences Mg homeostasis and adrenal medullary function in SHR-SP. Further, SHR SP appear resistant to any blood pressure lowering effect of Ca irrespective of NaCl intake. PMID- 3353398 TI - Type I and type III collagen content of healing wounds in fetal and adult rats. AB - Full-thickness, dermal wounds were surgically created on the dorsa of fetal rats on the 17th day of gestation. The granulation tissue which developed after 2 days (19 days of gestation) was harvested from six to nine animals and pooled and the collagen was extracted with 0.5 M acetic acid and acetic acid plus pepsin. The ratio of type III:type I collagen was estimated from densitometer scans of electrophoretically separated alpha-chains. Full-thickness (to fascia depth) wounds were also produced on the dorsa of adult rats and granulation tissue which had developed for different periods of time up to 30 days was excised. Relative proportions of type III and type I collagen were assessed in normal and granulation tissues taken from the adult rats. Both fetal and adult granulation tissues have elevated type III collagen content but normal fetal tissue has a much higher content of type III than does normal adult tissue. PMID- 3353399 TI - Measurement of blood flow and oxygen consumption in the pelvic limb of fetal sheep. AB - In order to determine blood flow and oxygen consumption in the pelvic limb of fetal sheep, we applied the Fick principle of measurement of oxygen consumption in seven paired experiments in seven fetal sheep under normal conditions and after treatment with pancuronium bromide. Catheterization procedures, which minimized interference with the study limb circulation, avoided changes of catheter tip position during fetal movements,n and prevented collateral circulation to and from tissues not located in the pelvic limb, were utilized. Blood flow through the external iliac artery was measured by means of a transit time ultrasonic method. Six sample sets for oxygen content were drawn from the external iliac artery and vein during 45-min control period and repeated after neuromuscular blockade. Normal oxygen consumption under these experimental conditions was determined to be 20.7 +/- 1.9 (mean +/- SEM) mumole.min-1.100 g-1. Neuromuscular blockade caused oxygen consumption to decrease significantly (P less than 0.01) by 12% to 18.1 +/- 2.1 mumole.min-1.100 g-1 and decreased the average coefficient of variation from 15 to 8%. The data demonstrate that spontaneous skeletal muscle activity accounts for a significant amount of oxygen consumption, the level of which can vary widely over brief periods of time. These results suggest that such tissues with significant spontaneous changes in metabolic activity require repeated blood flow measurements with simultaneous determination of substrate arteriovenous differences to best describe metabolism under normal conditions. PMID- 3353400 TI - The effect of cold on adrenergic neurotransmission in canine saphenous arteries and veins. AB - The effect of severe cold (5 to 10 degrees C) on adrenergic neurotransmission was compared in the isolated cutaneous (saphenous) artery and vein of the dog. The vein contracted to sympathetic nerve stimulation at temperatures as low as 10 degrees C; higher temperatures were needed for the artery to contract. Both blood vessels contracted to exogenous norepinephrine at temperatures as low as 5 degrees C. However, the contractile response to exogenous norepinephrine was less in the saphenous artery, and contractions to high K+ solution were depressed by cooling more in the artery than in the vein. During electrical stimulation of the sympathetic nerves in saphenous arteries and veins previously incubated with labeled norepinephrine, progressive cooling from 37 to 5 degrees C caused a sharp decline in overflow of [3H]norepinephrine and its metabolites. However, overflow of labeled norepinephrine in both blood vessels continued at very cold temperatures. Thus the inability of the saphenous artery to contract to sympathetic nerve stimulation at 10 degrees C can be explained by a greater sensitivity of the arterial smooth muscle to the direct depressant effect of cold, rather than to a differential release or metabolism or norepinephrine in the arterial wall or a loss of responsiveness to norepinephrine at very cold temperatures. PMID- 3353401 TI - Disruption of endoplasmic reticulum is the primary ultrastructural lesion of the pancreas in the selenium-deficient chick. AB - Severe uncomplicated selenium (Se) deficiency was produced in chicks by feeding, from 1 day of age, a purified diet that contained 0.010 ppm Se but was adequate with respect to all other known nutrients. The deficiency was characterized by depressions in rate of growth and efficiency of feed utilization and by reductions in the plasma activity of Se-dependent glutathione peroxidase (SeGSHpx) by 85-97% from levels in chicks fed the basal diet supplemented with 0.20 ppm Se as Na2SeO3. Histological observations of the target organ of Se deficiency in the chick, i.e., the pancreas, using transmission electron microscopy, showed severe losses of endoplasmic reticulum (ER) and absence of secretory granules in acinar cells of Se-deficient animals. These effects were not uniform within individuals, as Se-deficient pancreases also showed areas of unaffected acini. By 14 days of age, Se-deficient pancreases contained many apparently undifferentiated cells, which were absent from pancreases of Se-fed chicks. It is noteworthy that abnormal mitochondria were not observed in any pancreas sections. It is concluded that the metabolic consequences of severe uncomplicated Se deficiency in the chick result from the disruption of ER and loss of functional acinar cells, rather than to damage to mitochondria as previously suggested. PMID- 3353402 TI - Parents in the anaesthetic room: a blessing or a curse? PMID- 3353403 TI - Violence and the organisation. PMID- 3353404 TI - 'Back to nursing'--a sham. PMID- 3353405 TI - Extra-corporeal shock wave lithotripsy. PMID- 3353406 TI - The unit-dose system of drug distribution. PMID- 3353407 TI - Mental confusion in the dying patient. PMID- 3353408 TI - Natural healing processes: an essential update. PMID- 3353409 TI - Bereavement: the needs of the terminally ill patient's family. PMID- 3353410 TI - A parents' guide to weaning. PMID- 3353411 TI - Mandatory continuing education: your views. PMID- 3353412 TI - Nurse/psychotherapists: their role in the community mental health team. PMID- 3353413 TI - Drug update: antibacterial agents. PMID- 3353414 TI - Neurochemical lesion of the nucleus locus coeruleus increases neophobia in a specific exploration task but does not modify endocrine response to moderate stress. AB - In order to test more specifically the role of the nucleus locus coeruleus (LC) in reaction to novelty, rats with bilateral 6-hydroxydopamine lesions of this nucleus, vehicle injected rats and non-operated animals were tested in the open field and in the Hughes apparatus where motor activity is recorded in both a familiar and a non-familiar environment. In the open-field, the LC lesioned animals were significantly less active. A similar decrease of locomotor activity was observed in the Hughes test: the number of passages between the two boxes of the LC lesioned rats was significantly decreased. Likewise when the locomotor activities in the two boxes were pooled, the activity of the rats with lesions was significantly lower than the activity of the control rats, but in this case the locomotor deficit appeared only in the familiar box, the locomotor activity in the novel enclosure being the same in both LC lesioned and control animals. This result suggests that exploratory induced locomotion is not disturbed by the locus coeruleus lesion. The significant locomotor deficit showed by the LC lesioned rats in the familiar box could be due to an increased immobility induced by the stressful situation. Moreover, the deficit observed was the same whether the behavioral test began 4 days or 4 weeks after the lesion. Finally, at the end of the experiment, all rats were submitted to a moderate novel environmental stress and blood samples collected to measure the plasma levels of different stress hormones (ACTH, glucocorticoids, PRL, catecholamines).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353415 TI - Behavioral factors in development of tolerance to ethanol's effects. AB - Dose-effect analyses were used to monitor the development of tolerance for ethanol's effects on FR30 operant performance in rats under different conditions of chronic ethanol exposure: (a) pre-session ethanol injections (PRE) vs. post session ethanol injections (POST) in Experiment 1; and (b) an ethanol liquid diet (ED) vs. a control diet (CD) in Experiment 2. The PRE and ED groups developed tolerance at the conclusion of the chronic regimens, which declined by six months but not to baseline levels. These data suggest that tolerance results from learned compensatory adjustments (through intoxicated practice) to ethanol's disruptive effects. The POST, but not the CD, group developed a progressively increasing degree of tolerance after several ethanol challenge tests. These results suggest that some threshold level of passive ethanol exposure in the POST group interacted with their limited intoxicated practice. Finally, the tolerance developed under intoxicated practice conditions did not appear to reflect a generalized tolerance to rate-reducing properties of drugs, changes in ethanol kinetics, or age-related changes. PMID- 3353416 TI - The effect of breakfast on social behavior and brain amine metabolism in vervet monkeys. AB - Two groups of vervet monkeys were fed, on alternate days, either before or after a morning observation period. This enabled us to determine changes in behavior when the animals were fed a nutritionally balanced breakfast of monkey chow. Feeding did not alter the proportion of behaviors that were social or non-social, but had a marked effect on individual behaviors. Feeding increased active behaviors among the adult animals except for the vervets who were lowest in the social hierarchy in each cage. For some of the individual behaviors that were altered by feeding, the changes were most marked early on in the observation period, when the animals were still feeding. Other behavioral changes were seen only later in the observation period, a time course consistent with a food mediated change in brain biochemistry. A parallel biochemical experiment showed that feeding decreased the levels of tryptophan and 5-hydroxyindoleacetic acid in the CSF. Our data indicate that feeding can influence both brain biochemistry and behavior. The behavioral changes may be influenced by social and psychological factors as well as changes in brain biochemistry. PMID- 3353417 TI - Protection by the calcium antagonist Wy-47,037 against stress ulceration in the rat. AB - Wy-47,037, a novel compound with both intracellular and extracellular calcium blocking properties, was evaluated for its effects on cold/restraint stress induced ulceration in the rat. Wy-47,037 dose-dependently inhibited ulcerogenesis; with an ED50 of 8 mg/kg, PO, it was approximately twice as potent as nitrendipine (ED50 = 15 mg/kg). Wy-47,037 also reduced basal gastric acid secretion (ED50 = 7 mg/kg) and gastrointestinal motility (ED50 = 16 mg/kg). It is thus possible that Wy-47,037's alteration of basal gastric acid secretion and/or of gastrointestinal motility may contribute to its therapeutic efficacy against stress induced ulcer formation. PMID- 3353418 TI - Pressure reversal of the depressant effect of ethanol on spontaneous behavior in rats. AB - This study deals with the interaction between high pressure and a sub-hypnotic dose of ethanol in rats. Male Sprague-Dawley rats were given either ethanol 1.5 g/kg or saline IP and subsequently exposed to 1 atmosphere absolute pressure (ATA) air or to 1, 12, 24 or 48 ATA of helium-oxygen (heliox). The gas temperature was adjusted to offset ethanol and helium-induced hypothermia. Ethanol induced a characteristic unsteady pattern of locomotion which was completely reversed at 48 ATA, partially reversed at 24 ATA, but not affected at 12 ATA. Other behavioral effects of ethanol such as depression of total motor activity and rearing were similarly affected. Blood and brain concentrations of ethanol in the pressure groups did not differ significantly from concentrations measured in the 1 ATA groups. A similar pattern of reversal was observed whether the compression was initiated 4, 10 or 16 min after injection. These results show that hyperbaric exposure antagonizes the depressant effect of ethanol on spontaneous behavior in rats. This antagonism does not appear to be due to changes in ethanol distribution or elimination. PMID- 3353419 TI - Effects of selection delays on radial maze performance: acquisition and effects of scopolamine. AB - The effects of post-selection confinement (delays) on both the acquisition of performance and the response to the muscarinic blocker, scopolamine, were examined in an automated version of the eight arm radial maze. Long-Evans rats, exposed to post-selection delays of 0.5 sec (n = 4) or 100 sec (n = 4) during daily training trials did not differ in either the number of trials to acquire an accurate baseline of performance or in the amount of time required to obtain all eight food pellets. However, the pattern (delta-arm scores) of within-session arm selections demonstrated by the two groups of rats differed. Rats exposed to the 0.5-sec delay typically selected arms adjacent to arms from which they exited while rats exposed to the 100-sec delay were more likely to enter arms 2-removed from the exit arm. When scopolamine (0.03 to 1.0 mg/kg) was administered prior to testing, rats in the 100-sec delay group showed a greater reduction of accuracy and a larger increase in selection latency than rats in the 0.5-sec delay group. The differential effect of delay value on delta-arm scores was also eliminated in a dosage dependent manner with scopolamine. Scopolamine methylbromide (0.3 mg/kg) was found to have little effect on performance. In summary, the results indicate that the post-selection delay procedure is a sensitive and selective test for chemical-induced dysfunctioning of spatial memory in rats. PMID- 3353420 TI - An evaluation of the mechanism of scopolamine-induced impairment in two passive avoidance protocols. AB - The effects of several doses of the centrally-acting muscarinic antagonist, scopolamine, on subsequent learning and memory were examined using two versions of a standard light versus dark passive avoidance paradigm. The first protocol was employed primarily to examine the effects of scopolamine on the acquisition component of learning and memory as subject performance was measured during five successive (repeated) training trials. The second protocol employed a one-trial twenty-four hour retention task in which subjects were given one training trial followed by one testing trial twenty-four hours later. This latter test encompasses acquisition, retention, and recall components of learning and memory. Dose response studies indicated an effective dose range of 0.4-1.2 mg/kg with 0.8 mg/kg producing maximal performance decrement. Differential scopolamine treatment demonstrated that the drug's primary effect was on the acquisition component only under the present experimental protocols. Furthermore, scopolamine was not found to produce state-dependent learning. Animals administered scopolamine before training and testing failed to perform better than animals receiving pre-training administration only. PMID- 3353421 TI - An analysis of cocaine effects on locomotor activities and heart rate in four inbred mouse strains. AB - The effects of cocaine on Y-maze activity and heart rate have been examined in four inbred strains of mouse (BALB, C57BL, C3H and DBA). In addition, brain [3H] cocaine concentrations were measured at the time of maximal response to cocaine. Cocaine produced a dose-related increase in Y-maze cross activity in C3H, DBA and C57BL, with C3H mice being considerably more sensitive than DBA or C57BL. Cocaine was without effect on Y-maze cross activity in BALB mice. Cocaine produced a biphasic effect on rearing activity in C3H mice, a dose related depression in BALB mice, and was without effect on C57BL and DBA mice. At the highest dose studied (15 mg/kg), cocaine produced a small decrease in heart rate in C3H mice. Strain differences in behavior were maximal 15 minutes after a dose of 5 mg/kg, IP. At this dose and time interval, brain [3H]-cocaine concentrations were not significantly different among the four strains of mice. The results suggest a genetically-determined difference in CNS sensitivity to cocaine. PMID- 3353423 TI - Kainic acid lesions of the nucleus accumbens selectively attenuate morphine self administration. AB - The influence of kainic acid lesions of intrinsic and efferent neurons of the central medial nucleus accumbens on responding simultaneously maintained by food, water and morphine self-administration was assessed. Rats were trained on a multioperant baseline to respond on three different levers that resulted in either a food pellet, the presentation of a water dipper or an infusion of morphine. While responding on the morphine lever was related to dose (0.83-13.2 mg/infusion), increasing concentrations of the drug had little or no effect on responding maintained by food and water before the lesion. Bilateral infusions of the neurotoxin into the nucleus accumbens decreased morphine self-administration but did not appreciably alter food or water intake. Food extinction probes before the lesion produced significant increases in drug intake and decreases in responding on the water lever, but the neurotoxin lesion attenuated the food extinction induced decrease in water intake. These data suggested that kainic acid lesions of the nucleus accumbens decrease the reinforcing efficacy of morphine but do not alter the reinforcing properties of food and water. The neuronal systems potentially involved in mediating the reinforcing effects of environmental events are discussed. PMID- 3353422 TI - Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues. AB - Endogenous opioid peptides have been implicated in stress-induced analgesia and stress-induced feeding behavior. An earlier study from our laboratory showed that rats subjected to cold swim stress consumed significantly more food compared to controls. The present study describes changes in the levels of various opioid peptides in the central nervous system and periphery due to cold swim stress. Male Sprague-Dawley rats were subjected to cold swim stress (1 degree C for 5 min), then sacrificed by decapitation; brain, pituitary, adrenals and plasma were collected. Tissue extracts were assayed for opioid peptides by RIA. Cold swim stress resulted in analgesia which could be blocked by prior administration of naloxone, as observed by a tail-flick latency test. Cold swim stress caused a 42% decrease in pituitary beta-endorphin, but increased the level of this peptide in the hypothalamus and plasma by 36% and 337%, respectively. Dynorphin level decreased by 62% in the hypothalamus, but was not affected in the pituitary. Levels of Leu-enkephalin and Met-enkephalin decreased in the adrenal gland by 37% and 18%, respectively, but were not significantly affected in the CNS. These results indicate that cold swim stress has a differential effect on the level of CNS and peripheral opioid peptides, and that both central and peripheral opioid peptides may be important in stress-induced analgesia and feeding behavior. PMID- 3353424 TI - Effects of ethanol, barbital, and lorazepam on brain monoamines in rat lines selectively outbred for differential sensitivity to ethanol. AB - The acute effects of ethanol, barbital, and lorazepam on the synthesis and metabolism of brain monoamines were studied in the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) lines of rats, which have been selected for differential motor impairment after ethanol administration. The ethanol-sensitive ANT rats are also more sensitive than the ethanol-insensitive AT rats to the motor impairment caused by barbital and lorazepam. Ethanol increased, whereas barbital and lorazepam decreased, the synthesis of catecholamines in several regions of the brain. Ethanol did not affect the formation of DOPAC, whereas barbital and lorazepam reduced it. Similarly, the accumulation of 5-HTP was increased after administration of ethanol, but was decreased after administration of barbital or lorazepam. Ethanol, barbital and lorazepam decreased the formation of 5-HIAA. The rat lines did not differ in any of these responses. Some differences could, however, be demonstrated between the AT and ANT rats in the effects of the three drugs on the levels of the brain monoamines. Although the importance of these differences in the differential sensitivity to these drugs between the two lines is difficult to determine, the role of central monoaminergic mechanisms cannot be excluded. These findings also suggest that the motor impairment induced by ethanol, barbiturates, and benzodiazepines is probably not primarily based on the monoaminergic systems. PMID- 3353426 TI - Restricted feeding does not modify discriminative stimulus effects of morphine in the rat. AB - An experiment was performed to determine if the discriminative stimulus effects of morphine are modified by mild food deprivation, a condition that increases drug-reinforced behavior. Rats were trained to discriminate between SC injections of saline and morphine (3.0 mg/kg) in a discrete-trial shock-avoidance procedure. Stimulus generalization curves for morphine were then determined on three occasions by a cumulative-dosing procedure: before, during and after the body weight of the rats had been reduced to 86-87% of normal by restricted feeding. Food deprivation had little or no effect on the morphine generalization curve. Despite a close relationship between the reinforcing and discriminative stimulus properties of opioid drugs, stimulus control of behavior by morphine was not modified by a condition that enhances opioid-reinforced behavior. PMID- 3353425 TI - Functional responses to baclofen and 4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin 3-ol (THIP) in rats repeatedly treated with desipramine. AB - Subcutaneous chronic desipramine (DMI, 5 mg/kg once daily for 18 consecutive days) prevented subcutaneous THIP (20 mg/kg) reduction in body temperature but did not affect THIP behavioral depressant effect (open-field behavior). Repeated DMI treatment did not affect subcutaneous baclofen (2.5-10 mg/kg) reduction in body temperature and behavioral depression (open-field behavior). PMID- 3353427 TI - Scopolamine reverses haloperidol-attenuated lever-pressing for water but not haloperidol-attenuated water intake in the rat. AB - The operant lever-pressing response has previously (Ljungberg, Pharmacol Biochem Behav 27: 341-350, 1987) been found to be inhibited by lower doses of haloperidol than the corresponding consummatory act, i.e., water intake. In the present study it was found that the attenuation of the lever-pressing response caused by the neuroleptic, but not the attenuation of the water intake, could be counteracted by scopolamine. The results support the notion that blockade of operant responding by low doses of neuroleptics are probably related to the extra pyramidal side-effects of neuroleptics seen in the clinic, as both phenomena can be counteracted by anticholinergics. These results therefore conflict with the anhedonia hypothesis put forward as an explanation of the attenuating effects of neuroleptics in operant settings. The findings also have a clear bearing on the role of dopamine in feeding and drinking behavior, as the results implies that different aspects of the control of water intake (i.e., the operant vs. the consummatory phase) are governed by different mechanisms in the CNS. PMID- 3353428 TI - Naloxone and diprenorphine reduce responding for brain self-stimulation in a fixed-ratio schedule in rats. AB - Rats were implanted with bipolar stimulating electrodes in the midbrain-central gray area (MID-CG) and trained to lever-press for intracranial self-stimulation (ICSS) on a continuous reinforcement schedule (CRF). When behavior was stable, animals were tested in 30 min ICSS sessions following the administration of either naloxone or diprenorphine, both over the dose-range 0.001-10 mg/kg, or with vehicle. Following testing on the CRF schedule, animals were re-trained on a fixed-ratio:30 (FR:30) schedule. When behavior had again stabilized, testing with naloxone, diprenorphine and vehicle was repeated. In the CRF tests, neither naloxone nor diprenorphine had any effects on response rates over the 10,000-fold dose-range used. In the FR:30 tests, however, both drugs significantly reduced response rates at the 10 mg/kg dose, and the reduction produced by naloxone was significantly greater than that produce by diprenorphine. These results suggested that diprenorphine is qualitatively similar to naloxone in altering the rate of responding maintained by ICSS, but is less potent than the prototypical opioid antagonist in this paradigm. PMID- 3353429 TI - Effects of cigarette smoking on resting EEG, visual evoked potentials and photic driving. AB - The effects of smoking a cigarette (1.3 mg nicotine delivery) versus sham smoking were studied using EEG, visual evoked potentials (VEP), photic driving (PD) and heart rate (HR) in thirty young healthy male and female habitual cigarette smokers. Heart rate (HR) and exhaled carbon monoxide (CO) level were significantly increased by real as opposed to sham smoking. Real versus sham smoking significantly increased relative power in the beta bands, reduced alpha and theta activity to a small but significant extent, but had no effect on delta activity. Dominant EEG alpha frequency was significantly increased by real as opposed to sham smoking. Smoking produced no significant mean change in PD or VEP. However, correlational analysis indicated that variables such as basal CO level, residual butt filter nicotine, basal electrocortical response level and personality, predicted to varying degrees the magnitude and direction of the effect of smoking on VEP, PD and EEG. PMID- 3353430 TI - Nicotine increases thermogenesis in brown adipose tissue in rats. AB - This study has tested the hypothesis that nicotine might increase thermogenesis in rats by activating the sympathetic nervous system which supplies brown adipose tissue. Three hours after a single injection of nicotine, both the turnover of norepinephrine and the binding of the purine nucleotide, guanosine 5'-diphosphate (GDP) to mitochondria from brown adipose tissue were significantly increased. After 11 days of treatment with nicotine, the turnover of norepinephrine and the GDP binding to mitochondria from brown adipose tissue both remained elevated but weight gain was not different. These data are consistent with the hypothesis that nicotine may have part of its effect through changes in thermogenesis involving sympathetic nervous activation of peripheral thermogenic tissues such as brown adipose tissue. PMID- 3353431 TI - Naloxone decreases ethanol consumption within a free choice paradigm in rats. AB - The effect of subcutaneous naloxone administration on the consumption of a weak ethanol solution in rats on the three consecutive days (testing days) was investigated using a behavioral paradigm which includes a first forced ethanol exposure (conditioning day) followed by a two-bottle ethanol/water choice procedure. Besides reducing fluid intake, naloxone treatment prior to forced ethanol exposure interferes with the acquisition of ethanol preference. Post conditioning naloxone administration fails to affect ethanol preference. Administration of naloxone prior to the first testing session induces a reduction on total fluid intake, at the day of treatment; a decrease on ethanol preference throughout the three consecutive testing days is also observed with the higher dose of the antagonist (5 mg/kg). An involvement of endogenous opioids in ethanol consumption is suggested through the modulation of alcohol reinforcement or the affective quality of the gustatory cue. PMID- 3353432 TI - Behavioral interactions between nicotine and caffeine. AB - Nicotine (0.01-1.0 mg/kg) was administered alone and together with three doses of caffeine (3.0, 10.0 and 30.0 mg/kg) to rats responding on a fixed-interval 2-min schedule of food reinforcement. The effects on overall response rate depended on dose: with the 3.0 mg/kg dose of caffeine response rate was increased by an amount approximately equal to the effect of the caffeine alone, while 10.0 mg/kg of caffeine reduced and 30.0 mg/kg completely abolished the increases in response rate produced by nicotine. The within-interval pattern of responding was affected in a similar, dose-related manner by both nicotine and caffeine alone. These effects added to produce large changes in the pattern when high doses of the two drugs were co-administered. The changes comprised increases in lower response rates in the early and middle parts of the interval and proportionally smaller increases or decreases in the higher rates occurring later in the interval. The interaction between nicotine and caffeine cannot be characterized simply, but depends on the particular aspect of behavior under examination. PMID- 3353433 TI - Prevention of the convulsant and hyperalgesic action of strychnine by intrathecal glycine and related amino acids. AB - Intrathecal administration of 25 micrograms strychnine induced consistent sensory and motor behavioral events in rats. Sensory events included scratching and biting the lower half of the body, spontaneous vocalizations and skin hyperalgesia, evidenced by vocalization and reflex scratching in response to stimulation with a 5.5 g von Frey fiber. This mild stimulus failed to elicit vocalizations in the preinjection condition. Strychnine induced two types of motor seizures: (1) falling over with tail whipping and (2) convulsions. The effect of equimolar doses of glycine (G) and some related amino acids: beta alanine (A), taurine (T) and betaine (B) on the strychnine syndrome was tested by administering them (intrathecal route) along with strychnine. T and G but not B significantly decreased most of the sensory events triggered by strychnine. All amino acids significantly decreased the incidence and duration of convulsions; T and B abolished them. A decreased vocalizations and skin hyperalgesia but synergized with strychnine to facilitate scratching and self biting. These results are consistent with findings that G, A and T displace strychnine from its binding sites in the CNS. PMID- 3353434 TI - Inhibition of feeding and hoarding behaviors by phenylpropanolamine in the adult rat. AB - The mechanism by which phenylpropanolamine (PPA) reduces feeding and body lipid is unknown. To determine if malaise associated with PPA treatment mediates its anorexic action, the present study compared the actions of PPA on feeding and hoarding behavior with that of lithium chloride at dose levels that induce comparable conditioned taste aversions. Adult male rats were injected (IP) 30 minutes prior to a test of feeding and hoarding behavior with either 0.9% saline, 32 mg/kg lithium chloride or with 10 mg/kg, 20 mg/kg or 40 mg/kg PPA. Although 32 mg/kg lithium chloride was without effect on either feeding or hoarding behaviors, PPA significantly suppressed both behaviors. These results do not support the notion that malaise is a critical aspect of the anorexic property of PPA and that hoarding behavior may represent a sensitive index of anorexic drug potency. PMID- 3353435 TI - Yohimbine potentiates cold-water swim analgesia: re-evaluation of a noradrenergic role. AB - Continuous cold-water swims (CCWS) elicit a nonopioid and neurohormonal analgesia which displays adaptation. The norepinephrine (NE) system has been implicated since parallel alterations in NE occur following acute and repeated CCWS exposure, and since CCWS analgesia is reduced by locus coeruleus lesions and is potentiated by clonidine and desipramine. The present study evaluated the effects of the alpha-2 NE receptor antagonist, yohimbine upon CCWS (2 degrees C for 3.5 min) analgesia on the jump and tail-flick tests, CCWS hypothermia, and basal nociceptive and thermoregulatory measures in rats. Yohimbine (0.1-2.0 mg/kg, IP) dose-dependently increased basal jump thresholds and potentiated CCWS analgesia: these effects appeared to be additive. Yohimbine potentiated CCWS analgesia on the tail-flick test without altering basal latencies. Yohimbine failed to alter either CCWS hypothermia or basal thermoregulation. Since yohimbine and clonidine, an alpha-2 NE receptor antagonist and agonist respectively, similarly potentiate CCWS analgesia, it appears that NE effects are orthoganol to the intrinsic system mediating CCWS. PMID- 3353436 TI - "Crack smoke" is a respirable aerosol of cocaine base. AB - The smoking of cocaine base [corrected] ("crack") has emerged as a significant substance abuse problem. A detailed characterization of cocaine smoke is a prerequisite for studies of its pharmacokinetics, abuse potential and toxicity. Model pipes were used to generate cocaine smoke analogous to that inhaled by human "crack" abusers. Using procedures to minimize pyrolysis, cocaine base smoke was determined to be 93.5% cocaine particles with the remainder being cocaine vapor. The average particle size generated from all model pipes was 2.3 mu which is small enough to ensure deposition into the alveolar region of the human lung. Although this particle size is eminently respirable [corrected] by primates, a much smaller fraction will reach the alveolar region of rodents. Special generating procedures would therefore be required to expose rodents to meaningful doses of airborne cocaine that mimic the rapid absorption achieved by "crack" smokers. PMID- 3353437 TI - Blockade of brain M2 muscarinic receptors lowers blood pressure in spontaneously hypertensive rats. AB - Injections of the M2 muscarinic receptor antagonist 4-diphenylacetoxy-N methylpiperidine methiodide (4-DAMP; 1.5-40 micrograms) into the cerebral ventricles of urethane-anesthetized rats caused a dose-related inhibition of the pressor response to intravenously injected physostigmine. A similar reduction was obtained with 1/80th the dose of methylatropine, but not with the selective M1 antagonist pirenzepine. Intraventricular injection of 4-DAMP (6.25-25 micrograms) caused a dose-related reduction in blood pressure in unanesthetized spontaneously hypertensive rats (SHR), but not in normotensive controls. Systolic pressure fell 42 +/- 6 mm Hg at the 25-micrograms dose. Pirenzepine did not lower blood pressure in SHR and inhibited the antihypertensive effect of 4-DAMP. PMID- 3353439 TI - Antipyrine absorption and disposition in the elderly. AB - Twelve young (24-41 years) and 11 elderly (62-77 years) volunteer subjects received a single 1.0-gram dose of antipyrine on three occasions: intravenously, orally in the fasting state and orally following a standard breakfast. Plasma antipyrine concentrations were determined for 24 h after each dose. Compared to young males, elderly men had significantly prolonged elimination half-life (17 vs. 11 h, p less than 0.025) and reduced clearance (32 vs. 54 ml/min, p less than 0.06). However, elderly and young women did not differ in half-life (12 vs. 11 h) or clearance (37 vs. 44 ml/min). After oral dosage in the fasting state, young and elderly groups (regardless of gender) did not differ in peak plasma antipyrine concentration (Cmax) or time of peak concentration (Tmax). Absolute bioavailability was not significantly less than 100% and was not related to age. Postprandial oral dosage of antipyrine caused reduced Cmax and prolonged Tmax in all groups, but absolute bioavailability was not significantly less than 100%. Again, there were no age-related differences. Although aging may lead to reduced clearance of antipyrine among men, there is no evidence that old age is associated with impairment of the rate or extent of antipyrine absorption from the gastrointestinal tract. PMID- 3353438 TI - Propylthiouracil disposition in older hypothyroid patients. AB - The pharmacokinetic disposition of propylthiouracil (PTU) after a single oral dose was studied in 6 severely hypothyroid patients. Severity of disease, as indicated by thyroid-stimulating hormone concentration, was inversely related to plasma clearance of PTU. There were trends to increased apparent volume of distribution and plasma half-life for PTU as a function of age. The large apparent volume of distribution for PTU in these patients compared to euthyroid and hyperthyroid subjects, after a single drug dose, suggests that hypothyroidism as well as chronic drug ingestion must be considered as possible factors mediating this change. PMID- 3353440 TI - Influence of tetanus and typhoid vaccines on hepatic drug metabolism. AB - Several experiments suggested that vaccines might inhibit liver drug-metabolizing enzymes, an assumption in agreement with other findings obtained with most immuno enhancing agents. A direct, non-specific activation of macrophages with subsequent release of interleukin 1 may account for this inhibition. The purpose of the present study was to investigate whether tetanus and typhoid vaccines exerted such an influence on pentobarbital sleeping time in mice and antipyrine elimination in rabbits, both in vivo correlates of the activity of these enzymes. It is shown that tetanus (unlike typhoid) vaccination in both species can lead to a marked but transient impairment of hepatic drug metabolism in these conditions. The reason for this discrepancy is unclear. The assumption that aluminium hydroxide might play a critical role, as this adjuvant is included in the formulation of tetanus vaccine in contrast to that of typhoid vaccine, is not supported by our findings since aluminium hydroxide alone failed to exert any influence in our experimental conditions. Further studies are therefore warranted to elucidate the mechanism of this inhibition of the activity of hepatic drug metabolizing enzymes. PMID- 3353441 TI - Protection by opioids against gastric lesions caused by necrotizing agents. AB - The synthetic opioid met-enkephalin analog [D-Ala2, MePhe4, Met(0)5ol] enkephalin (DAMME) and the opiate morphine injected intraperitoneally to rats at doses of 0.5-2 and 5-20 mg/kg, respectively, showed a protective effect on gastric damage induced by oral administration of necrotizing agents (0.6 N HCl or 0.2 N NaOH solutions, 1 ml/rat). The protection was prevented by naltrexone (10 mg/kg s.c.), an opioid antagonist with long-lasting activity. Histological sections of mucosal samples from animals pretreated with morphine (10 mg/kg i.p.) and DAMME (1 mg/kg i.p.) showed less alteration of the columnar epithelium, with a normal glandular structure, than untreated rats. A mediation of prostaglandins is suggested, since indomethacin (10 mg/kg s.c.) significantly reduced the protective effects of opioids. PMID- 3353442 TI - Antiarrhythmic and arrhythmogenic actions of methyl lidocaine during the recovery phase after canine myocardial infarction. AB - Programmed electrical stimulation was used to evaluate the electrophysiologic and antiarrhythmic actions of methyl lidocaine in both conscious and anesthetized dogs, 4-7 days after myocardial infarction. When administered to animals demonstrating sustained ventricular tachycardia (n = 6), methyl lidocaine (5 and 10 mg/kg i.v.) prevented the induction of the original ventricular tachycardia in 2 dogs, and in the remaining 4 dogs slowed the tachycardia (cycle length 163 +/- 18 ms vs. 198 +/- 11 and 219 +/- 11 ms, respectively, p less than 0.05). New morphologic forms of sustained tachycardia were observed after drug administration in 4 of 6 experiments. When administered to animals developing only nonsustained ventricular tachycardia or no arrhythmias with programmed stimulation, methyl lidocaine administration enabled programmed stimulation to produce monomorphic sustained ventricular tachycardia in 10 of 13 experiments. The drug increased activation delays in both normal and ischemically injured epicardium, with larger activation delays always observed in ischemically injured tissue. The drug increased refractoriness in ischemically injured myocardium without altering refractoriness in normal tissue. The data suggest that the depression of conduction and prolonged refractoriness produced by methyl lidocaine in ischemically injured tissue may extinguish or slow some forms of ventricular arrhythmia while promoting the formation of new reentry pathways. PMID- 3353443 TI - Effect of chronic dietary treatment with L-tryptophan on the development of renal hypertension in rats. AB - Chronic dietary administration of L-tryptophan (2.5 and 5.0 g/100 g food) to rats provided significant protection against the development of hypertension induced by bilateral encapsulation of the kidneys with latex envelopes. Lower doses of tryptophan (0.5 and 1.0 g/100 g food) attenuated the rate of elevation of blood pressure, but failed to maintain systolic blood pressures at levels significantly below that of untreated renal hypertensive controls. The body weight of the rats was not affected significantly by treatment with any dose of tryptophan used. Chronic treatment with tryptophan also protected against the reduced urinary concentrating ability during a 24-hour dehydration that characteristically accompanies renal encapsulation. A modest (5-8%) effect of treatment to reduce cardiac hypertrophy was also observed. The mechanism of the antihypertensive effect of tryptophan is not revealed by these studies although they rule out the possibilities that reduction in sodium intake and/or reduction in body weight may be important factors. PMID- 3353444 TI - Generation of photon energy deposition kernels using the EGS Monte Carlo code. AB - The EGS Monte Carlo code was used to generate photon energy deposition kernels which describe the energy deposited by charged particles set in motion by primary, first scattered, second scattered, multiple scattered and bremsstrahlung plus annihilation photons. These were calculated for a water medium irradiated with monoenergetic photons with energies in the range 0.1-50 MeV. In addition to the primary energy deposition kernels, primary charged particle transport was further characterised by computing the effective centre of the voxels, and the effective penetration depth, effective radius and effective lateral distance travelled by these particles. The dose per unit collision kerma for parallel monoenergetic primary photons beta' was calculated. Additional applications of the energy deposition kernels are discussed. PMID- 3353445 TI - Practical limits on the biomagnetic inverse process determined from in vitro measurements in spherical conducting volumes. AB - A technique of locating current dipoles in spherical conducting volumes by determining the location of the magnetic field maximum and inverting the magnetic field equations was developed and the expected localisation errors were predicted. AC current dipoles were placed in spheres of uniform conductivity. Each dipole's magnetic field was measured and its location was calculated by determining the angle between the magnetic field null and maximum and using an iterative inverse solution to the magnetic field equations. Absolute agreement between predicted magnetic field strengths and actual magnetic field measurements was within 5%. A study of the effect of signal to noise ratio and number of data points in the analysis indicates that dipole localisation of approximately 1 mm is achievable for a signal to noise ratio greater than 10 decibels (S/N greater than 10 db). PMID- 3353446 TI - Can photography be used to measure isodose distributions of space irradiance for laser photodynamic therapy? AB - The space irradiance isodose distribution of light delivered in tissue by an interstitial optical fibre may be determined by photographing the light diffusing out of the tissue. Provided that a plane of symmetry is photographed, it is shown that there is no significant distortion of the isodose distribution measured in this way. Two series of photographs were taken to test the method. In one set, a partially reflecting film was used to simulate the presence of the missing tissue. Isodose distributions obtained were in agreement with the predictions of diffusion theory. The isodoses were "scaled' by measuring the space irradiance at one point with a bulb-tipped optical fibre. Optical parameters are deduced from the measurements. The method, which is simple and fast in use, should be of wide applicability. PMID- 3353447 TI - Laser ablation of discs of agar gel. AB - Discs of agar gel mixed with ink were used to study ablation effects with an argon laser as a light source. Varying amounts of ink were added resulting in a variation of the attenuation coefficient between 0.45 and 6.3 mm-1. For laser beam irradiation horizontally incident on a vertical sample, the average velocity of ablation was found to be approximately constant for thicknesses up to 1.7 mm. When the laser beam was directed vertically on a sample held horizontally, the vaporized debris present in the beam attenuated the incident laser energy to such a degree that the average ablation velocity decreased by a factor of approximately five. Horizontal beam experiments for various attenuation coefficients showed that an attenuation coefficient of about 1.7 mm-1 is optimal for fast penetration of discs thicker than 4 mm. Thus, based upon the optical properties of a given tissue, there may exist an optimum laser wavelength to maximise ablation velocity. PMID- 3353449 TI - Measurement of the PSF for a CT scanner: appropriate wire diameter and pixel size. PMID- 3353448 TI - Density-exposure conversion curve and microblackness characteristic in the radiological domain. PMID- 3353450 TI - Some electrical and fabrication properties of virgin and recycled A-150 tissue equivalent plastic. PMID- 3353451 TI - Statement from the 1987 Como meeting of the International Commission on Radiological Protection. PMID- 3353452 TI - The use of gamma functions in the calculation of organ perfusion functions for non-diffusible radioactive tracers. AB - This paper introduces a method for quantification of mean organ perfusion by the impulse response function using the experimental time-activity curves for the organ of interest and its supplying artery. These are approximated by gamma functions and a general expression for the impulse response function is then derived. In any particular case, the impulse response function can be calculated simply by insertion of the numerical parameters. The procedure combines speed with freedom from random measurement errors. As an example of a clinical application, the impulse response function of healthy brain tissue is calculated and some clinically important parameters are tabulated. PMID- 3353453 TI - A rapid method for the quantification of C, N and O in biomedical samples by proton-induced gamma-ray emission analysis applied to human placental samples. AB - A new fast, accurate and simple quantification method for C, N and O in biomedical samples by external-beam proton-induced gamma-ray emission analysis is presented. Concentration values for C, N and O in commercial standards of NBS bovine liver 1577a, IAEA animal muscle H-4 and IAEA horse kidney H-8 were determined using the new method. The concentrations of C, N, O, Na, Mg and P were determined from placental samples of 13 alcoholic mothers and from 16 abstinent controls. The values obtained for C, N, O, Mg and P were the first values ever obtained for human placentas. PMID- 3353454 TI - Estimation of effective dose equivalent to staff in diagnostic radiology. AB - The irradiation of staff in diagnostic radiology was simulated for conditions commonly encountered in fluoroscopy. Scattered radiation distributions were produced from diagnostic x-ray beams generated at tube potentials in the range 60 120 kVp, using the abdomen sections of a Rando phantom. Doses to a number of organs in the head and neck were measured using a Rando phantom loaded with lithium fluoride thermoluminescent dosemeters. The torso sections were placed on a water phantom on top of a stand, with film badge dosemeters positioned on the surface of the phantom at the forehead, neck, chest and waist, and the phantom was placed in the radiation field. Doses to organs in the torso were calculated from the waist-level film badge dosemeter reading using normalised organ dose data. Radiation doses to organs below a lead apron, when worn, were estimated from the unshielded dose values using a transmission factor appropriate to the quality of the scattered radiation. The effective dose equivalent (EDE) to the phantom was calculated for various x-ray beam qualities and lead apron thicknesses and compared with the film badge doses. The results indicate that a dosemeter worn at the waist/chest level under a lead apron generally underestimates the EDE. Conversely, dosemeters worn at the forehead/neck tend to overestimate the EDE. It is recommended that a dosemeter is positioned under a lead apron, if worn. PMID- 3353455 TI - Measurement of x-ray image intensifier sharpness in the x-ray department. AB - A method is presented for determining the modulation transfer function (MTF) of an image intensifier as it is found in the x-ray department. The image of an edge input into the image intensifier tube is photographed at the television camera port with a high quality camera and the photographic image scanned with a microdensitometer. Densitometric conversion enables the determination of the edge spread function and further calculation produces the line spread function and the MTF. A correction is made for the camera/lens/film/developer response function. Results from the use of the technique on over 25 x-ray image intensifiers in New Zealand hospital x-ray departments are presented and discussed. Most of the image intensifiers had been in use for more than 7 years. The low-frequency drop values were similar to reported values with an average value of 22%, but modulation values at 1 cycle/mm (the average value was 29%) were generally lower than values previously reported, indicating that the sharpness performance in the clinical environment is inferior to claims for new or state-of-the-art intensifiers. PMID- 3353457 TI - Effects of tendon pressure on alpha motoneuron excitability in patients with stroke. AB - The purpose of this study was to evaluate the effects of two intensities (5 and 10 kg) of continuous and intermittent Achilles tendon pressure on the H-reflex in eight hemiparetic subjects. A decrease in the H-reflex was interpreted as a depression in motoneuron excitability, a condition conducive for reducing muscle tone. The H-reflex measurements were obtained before, during, immediately after, and 2.5 minutes after tendon pressure application. Piecewise linear regression equations were used to evaluate the effects of four pressure conditions. The mean of the midpoints of the lines for each pressure condition was compared with prepressure baseline values by t tests and with the other pressure conditions by an analysis of variance. All four pressure conditions demonstrated H-reflexes less than prepressure baseline values, with three of the four conditions (5 and 10 kg of intermittent pressure and 5 kg of continuous pressure) being significantly less than prepressure baseline values (p less than .05). The analysis of variance revealed a significant difference among pressure conditions. Scheffe post hoc contrast comparisons revealed significant differences between intermittent and continuous pressure but not between 5 and 10 kg of pressure. The results of this study indicate that in these hemiparetic subjects, the H-reflex was depressed during both continuous and intermittent tendon pressure. Intermittent pressure was more effective then continuous, but 10 kg of pressure had no greater effect than 5 kg of pressure. The effects of pressure lasted only as long as the stimulus was present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353456 TI - Effects of a supervised home exercise program on patients with severe chronic obstructive pulmonary disease. AB - The purpose of this study was to analyze the effects of a home exercise program on physical work capacity and dyspnea during activities of daily living in patients with severe chronic obstructive pulmonary disease. Twenty patients with severe respiratory impairment were assigned in a stratified, random manner to an Exercise Group (n = 10) or a Control Group (n = 10). Patients in the Exercise Group performed the supervised home exercise program of daily mobility, strengthening, and endurance exercises. Patients in the Control Group were visited regularly by a physical therapist but did not follow the exercise program. Six patients were eliminated from the study, either because of death (n = 1) or noncompliance with experimental conditions (n = 5), leaving each group with seven patients. The results of a progressive bicycle ergometer test after 18 weeks showed a significant between-group difference in physical work capacity. The physical work capacity of patients in the Exercise Group had improved 3% and had deteriorated 28% for patients in the Control Group (p less than .05). The symptom-limited multistage step test and the Chronic Respiratory Disease Questionnaire showed no difference in the patients' physical work capacity or dyspnea during ADL. Although not conclusive, this study yielded some evidence for the beneficial effects of home exercise training on patients with severe chronic obstructive pulmonary disease. PMID- 3353458 TI - Effects of high voltage pulsed electrical stimulation on blood flow. AB - The purpose of this study was to determine whether high voltage electrical stimulation would increase blood flow to skeletal muscle in healthy subjects. Subjects were assigned to one of three groups: 1) an Electrical Stimulation (ES) Group (n = 16), 2) an Exercise (EX) Group (n = 14), or 3) a Control Group (n = 8). Isometric contractions were induced electrically at 30 Hz in the ES Group and performed volitionally in the EX Group for five minutes at intensities of 10% and 30% of predetermined maximal voluntary isometric contraction (MVC) efforts. Blood flow, heart rate, and blood pressure were unaffected in the ES Group, but blood flow and systolic blood pressure increased and decreased, respectively, for the EX Group at 30% of MVC. High voltage stimulation at a pulse rate of 30 Hz and at intensities needed to evoke contractions at 10% and 30% of MVC for plantar flexion did not increase blood flow at the popliteal artery. PMID- 3353459 TI - Relationship between antigravity control and postural control in young children. AB - The purposes of this study were 1) to determine the relationship between antigravity control (supine flexion and prone extension) and postural control (static and dynamic balance), 2) to determine the quality of antigravity and postural control, and 3) to determine whether sex and ethnic group differences correlate with differences in antigravity control and postural control in young children. I tested 107 black, Hispanic, and Caucasian children in a Head Start program, with a mean age of 61 months. The study results showed significant relationships between antigravity control and postural control. Subjects' supine flexion performance was significantly related to the quantity and quality of their static and dynamic balance performance, whereas prone extension performance was related only to the quality of dynamic balance performance. Quality scale measurements (r = .90) indicated that the children in this study had not yet developed full antigravity or postural control. The study results revealed differences between sexes in the quality of static balance and prone extension performance and ethnic differences in static balance, dynamic balance, and prone extension performance. PMID- 3353460 TI - Comparison of maximal isometric hip abductor muscle torques between hip sides. AB - A posturally induced "stretch weakness" of the right hip abductor muscles has been reported in many healthy right-handed persons in the literature. The purpose of this study was to test for differences in the maximal isometric hip abduction torque produced between hip sides across multiple hip abduction angles. The torques were measured on 40 healthy right-handed individuals using a specialized torque-testing table at hip abduction angles of -10, 0, 10, 20, 30, and 40 degrees. Statistical analysis of the results did not demonstrate a specific "weakness" of the right hip abductor muscles at the hip angle used to clinically test them. The results, however, did demonstrate statistically significant differences in the torque-hip angle slopes across hip sides. We hypothesized that these slope differences may result from muscle adaptation to lengths imposed by standing posture. We discuss how manual muscle testing procedures may bias the likelihood of encountering stretch weakness in muscles that are habitually maintained at near-maximal elongation. PMID- 3353461 TI - Evaluation of students' approaches to studying in a problem-based physical therapy curriculum. AB - The purpose of this study was to investigate the approaches to studying of first- and second-year students in a problem-based physical therapy program. The Short Inventory of Approaches to Studying was administered to 112 first-year students (66 female, 46 male) and 100 second-year students (62 female, 38 male). Ninety nine first-year students and 88 second-year students responded to the inventory, representing a return rate of 88%. The results of both groups were compared. Further comparisons were made with reported normative inventory scores and with inventory results reported of first-year students in a medical problem-based school. All comparisons were made using two-tailed t tests. The inventory scores proved similar in both year groups of physical therapy students and were more desirable than the normative values. The first-year physical therapy students' scores were similar to those of the first-year medical students reported to be desirable. It was concluded that the physical therapy students possess desirable approaches to studying. PMID- 3353462 TI - Survey of burn education in entry-level physical therapy programs. AB - We investigated the extent of burn education in entry-level physical therapy curricula and also collected information about oncology instruction. A questionnaire was sent to the directors of 96 entry-level physical therapy curricula, and 76 directors responded. Most of the respondents (98.7%) indicated that burn and cancer management warranted lectures. The programs that quantified instruction averaged 4.8 hours of burn-related medical and surgical lectures and 4.2 hours of burn-related physical therapy procedure lectures. The instructional time devoted to oncology was slightly less. Physicians presented the medical and surgical lectures in 36% of the curricula and provided instruction with physical therapists and nurses in 39% of the curricula. Physical therapists alone presented the lectures on physical therapy procedures in 83% of the curricula. Sixty-three percent of the respondents believed that new graduates could effectively treat both patients with burns and those with cancer, but other respondents attached various qualifiers to their responses. Some respondents thought that new graduates could not adequately treat patients with burns (12%) or cancer (8%). Suggestions for future physical therapy burn education are given. PMID- 3353463 TI - Craniosacral therapy and myofascial release in entry-level physical therapy curricula. AB - The purposes of this study were 1) to discover the extent to which craniosacral therapy (CST) and myofascial release (MFR) instruction are included in entry level physical therapy curricula; 2) to determine the amount of faculty and program director interest in such instruction; and 3) to determine what educational materials, if any, are desired. A one-page questionnaire was distributed to the program directors of 109 accredited entry-level physical therapy programs in the United States. Of the 95 respondents, 1 (1%) included a unit on CST only, 14 (15%) included a unit on MFR only, 14 (15%) included units on both CST and MFR, and 66 (69%) included neither. The highest percentages of programs with CST and MFR units were entry-level masters' degree programs and programs located in the Pacific Coast and Middle Atlantic regions. All of the units were presented within required courses, usually during the second year; most were taught by physical therapists. The greatest amount of instructional time was allotted for CST laboratory sessions (mean = 5.8 hours), and the least amount of time was allotted for MFR lectures (mean = 1.7 hours). The mos frequently cited reason for noninclusion of CST or MFR instruction was inadequate room in the current curricula. The most frequently requested materials were bibliographies and laboratory guides on CST and MFR. Implications of these findings are addressed, and suggestions for further research are given. PMID- 3353464 TI - Measures of thermal stress. PMID- 3353465 TI - Musculoskeletal deviations. PMID- 3353466 TI - Clinical measurement dialogue. PMID- 3353467 TI - Importance of Physical Therapy grows. PMID- 3353468 TI - [Psychotherapy in the education and practice of general practitioners and specialists in the USSR]. AB - For about three years psychotherapy has been introduced as a must for any medical student in the USSR. The author describes the policies behind this important step, its implementation, and first effects in detail. Psychotherapeutical services for the hospitalized, for crisis intervention, ambulant teams, its significance for surgery, and the delivery of psychotherapeutical short term programs in spas are described. The significance of psychotherapeutical work as a link between the specialized medical branches is stressed. PMID- 3353469 TI - [Development of the specialty fields of psychiatry and psychotherapy in East Germany]. AB - The development of psychiatry and/with psychotherapy ever since the beginning of the German Democratic Republic after WW2 is described and analysed. The author's main focus is on the confrontation, addition, and cooperation of both the classical medicine of matters and medicine of mind with conflicting, and at least varying paradigmatic reference. The pro and cons on shock therapy are discussed as a crucial point, here. The author holds that shock therapy interferes with the basics of a therapy where the patient is an integral and responsible part of the work as the mode of such treatment annihilates the Leitmotiv of psychotherapy within the framework of social psychiatry. PMID- 3353470 TI - [The patient in psychotherapy]. AB - Within the process of individual psychotherapy the author stresses the importance of understanding the initial everyday life view of "what is about being sick" for to establish a working, and cooperative setting. Thus, a three step procedure has been developed to guide the patient to a self responsible attitude toward conflicts and disease well at variance with common beliefs about healing, and the roles of the professional and his client herein. PMID- 3353471 TI - [Role of the home visit in the therapeutic program involving families of schizophrenic patients in Krakow]. AB - The authors report about a long term practical program involving the families of schizophrenic patients in the therapeutical context. They argue for advocacy of the two, both patient and "his" family. Detailed hints with theoretical backing are given to find a way of common sense for the patient, the family, and the therapists to gain a common, though not oversimplified and complexity reducing working context. PMID- 3353472 TI - [Occupational rehabilitation of psychiatrically handicapped patients in Leningrad, USSR: a visit to the Bechterew Psychoneurologic Institute]. AB - With reference to a recent reader on rehabilitation for the chronically mentally ill in the German Democratic Republic and the USSR the authors travelled to Leningrad, USSR, to learn about the efforts to integrate rather than add up multidisciplinary approaches to work rehabilitation. The authors found a sheltered workshop for about 400 patients where much of the principles of work rehabilitation obviously work: flexible and manyfold work, well adapted to the varying standards of the patients both unskilled workers and patients with academic background. The workshop being one branch of the nationally significant Bechterev Institute for Psychiatry and Neurology also transfers patients to the general workforce where rehabilitation patients are paid a 125% salary. Both the optimistic atmosphere and the economically self supporting shop give good reason to learn more about rehabilitation for the chronically ill in the USSR and the efforts to progress. PMID- 3353473 TI - [Goals and methodology of research on the rehabilitation of psychiatric patients as a comprehensive interdisciplinary project--content and system of data processing]. AB - The authors describe and discuss the problems of a current long term international comparative study on rehabilitation for the mentally ill. Above all methodology of computerized data sampling should not interfere with the complex holistic structure of the underlying theory of rehabilitation. Thus first theoretical assumptions are explained emphasizing a holistic approach. With critical reference to earlier efforts and studies elsewhere structure of data organization is described with direct reference to the documentary sheets for case documentation use. The documentation form developed enhances precision of task definition, interdisciplinary work, self control for the professional, and the establishing of new hypothesis. PMID- 3353474 TI - Scalar expectancy theory and choice between delayed rewards. PMID- 3353475 TI - Feature analysis in early vision: evidence from search asymmetries. PMID- 3353476 TI - "Abnormal fusion" of stereopsis and binocular rivalry. PMID- 3353478 TI - Psychophysiology begins its 25th year of publication. PMID- 3353477 TI - Discovering functionally independent mental processes: the principle of reversed association. PMID- 3353479 TI - Evaluation of a new ambulatory blood pressure monitor (Accutracker 102): laboratory comparisons with direct arterial pressure, stethoscopic auscultatory pressure, and readings from a similar monitor (Spacelabs Model 5200). PMID- 3353480 TI - Personality and individual differences in spinal motoneuronal excitability. PMID- 3353481 TI - Baroreceptor stimulation alters pain sensation depending on tonic blood pressure. PMID- 3353482 TI - Enhanced P3 evoked potentials and longer P3 recovery times in psychopaths. PMID- 3353483 TI - Heart rate acceleration and its relationship to total serum cholesterol, triglycerides, and blood pressure reactivity in men with mild hypertension. PMID- 3353485 TI - Attentional effects on sexual arousal. PMID- 3353484 TI - Habituation of the skin conductance response to strong stimuli: a twin study. PMID- 3353486 TI - The effects of task on the modulation of event-related potentials by word repetition. PMID- 3353487 TI - Electrodermal lability predicts presentation rate effects and stimulant drug effects on paired associate learning in hyperactive children. PMID- 3353488 TI - Eye movements and the detection of sleep onset. PMID- 3353489 TI - On the validity of heartbeat tracking tasks. PMID- 3353490 TI - How many blood pressure measurements are enough? An application of generalizability theory to the study of blood pressure reliability. PMID- 3353491 TI - Nursing shortage affecting salaries. PMID- 3353492 TI - DNA denaturation kinetics in CHO cells exposed to different X-ray doses and after different repair intervals using the alkaline unwinding technique. AB - The kinetics of DNA denaturation in alkaline solution (pH 12.2) was studied in CHO cells using the alkaline unwinding technique. After X-ray doses of 0, 3, 5 and 9 Gy, the kinetics of alkaline denaturation was found to be independent of the number of induced strand breaks confirming earlier studies on this subject. In addition, the denaturation kinetics measured in cells exposed to 9 Gy were found to be identical for different repair intervals. This result shows that for the three different classes of DNA strand breaks described previously (Dikomey and Franzke 1986a) strand separation in alkaline solution occurs at the same kinetics. As a consequence, the relationship between the numbers of strand breaks and the fraction of remaining double-stranded DNA is considered the same for the three different classes. PMID- 3353493 TI - Chromosomal effects in lymphocytes of 400 kV-substation workers. AB - In a previous study we found an increased rate of chromosomal aberrations in substation workers. To follow up this finding we in this study present data from 38 employees of electric power companies; 19 of the subjects worked with the repair and maintenance of circuit breakers and disconnectors in 400 kV substations. The other 19 served as controls and were only exposed to normal environmental electromagnetic fields. Coded blood samples were sent to a laboratory for determination of the rate of chromosomal aberrations (CA), sister chromatid exchanges (SCE), and cells with micronuclei (MN). Compared to the control group the exposed men displayed a statistically significant increase in CA and cells with MN. No increase was found in the frequency of SCE. Since "in vitro" studies of lymphocytes exposed to transient electric currents (spark discharges) produced similar results the increase in chromosomal damage in substation workers may be associated with exposure to transient electric currents during work. PMID- 3353494 TI - The effect of glycolysis inhibitors on the radiation response of CHO-K1 cells. AB - Exposure of CHO-K1 cells to three different inhibitors of glycolysis, prior to treatment with a single dose of ionising radiation, reduced their survival. The effects were concentration-dependent but occurred under all conditions where cells were exposed to the inhibitors prior to irradiation. The results are similar to those obtained by this group when glycolysis was altered using analogues of D-glucose or by blocking the pyruvate----lactate reaction using added lactate or oxamate. They support data from other workers suggesting a role for energy metabolism in the final expression of radiation damage. PMID- 3353495 TI - Microanalytical study of thorium 232 deposits in bone marrow and liver. AB - Analytical microscopy was used to study the distribution and chemical composition of thorium deposits in bone marrow and liver after injection of thorium dioxide and thorium nitrate. Thorotrast (thorium dioxide) was identified as being localized in bone marrow macrophages of a patient who had undergone cerebral arteriography forty two years ago. Large thorotrast deposits were also present in liver cells. We show that non-colloidal thorium (thorium nitrate) injected in rats concentrates in a non soluble form in bone marrow macrophages, hepatocytes and Kupffer cells. These deposits of thorium associated with phosphorus can be explained by the formation of thorium phosphate in lysosomes and we demonstrate that they remain in tissue for a long time. Microanalysis was performed with ion microscopy, and electron probe microanalysis by X ray spectrometry, which can identify and localize thorium and associated elements at cellular or intracellular level. PMID- 3353496 TI - Effect of plutonium-239 on the mitotic activity of mouse bone marrow cells. AB - Mitotic index of the bone marrow cells was studied in femoral bone marrow of mice given 313 kBq 239Pu kg-1. The attention was turned to the femoral midshaft and the mitosis concentration, intensified by Colcemid stathmokinetic effect, was evaluated in a sampling field from endosteal surface to the central venous canal, throughout 68 weeks. It has been found that the plutonium effect in the sampling band is rather uniform except the points in subendosteal zone early after plutonium injection, where the mitotic index was reduced in such a way that the mitotic gradient, observed in controls, was affected. The mitotic activity in femoral diaphysis of plutonium injected mice was mobilized approximately till the 30th week of contamination. Later it deteriorated progressively. The results are discussed and should not be regarded as representative for the entire bone marrow hemopoiesis. PMID- 3353497 TI - It is time to reopen the question of thresholds in radiation exposure responses. PMID- 3353498 TI - RIF-1 tumor treatment in anesthetized mice with minimal effects on blood flow and hypoxia. AB - The injectable anesthetic etomidate and a clip that facilitates hyperthermia by water bath immersion (the "Gibbs clip") were evaluated for their suitability with subcutaneous flank RIF-1 tumors in C3H/HeJ mice. For tumors between 100 and 250 mg (mean, 160 mg), etomidate at 40 mg kg-1 ip did not significantly increase the radiobiologic hypoxic fraction (RHF); as calculated from an in vitro assay after treatment in vivo the RHF increased from 0.06 (95% C.I.:0.03-0.13) to 0.08 (0.04 0.16). In contrast, for larger tumors (270-650 mg; mean, 400 mg) etomidate increased the RHF from 0.08 (0.04-0.17) to 0.28 (0.14-0.60). Holding 250-mg-or less tumors 3-mm laterally away from the flank in an X-ray jig did not significantly reduce tumor blood flow as inferred from the clearance rates of Xe, but the RHF of 0.15 (0.08-0.26) was significantly (P less than 0.05) greater than the RHF in unanesthetized mice, although not the RHF in anesthetized mice. The Gibbs clip, which folded skin around a tumor to enhance thermal conduction from a water bath, did not impair the increase in tumor blood flow in response to the cardiovascular arousal associated with exposure to a hyperthermic stimulus. Intratumor temperature was within 0.25 degrees C of bath temperature 3 min after the tumor and clip were immersed, but only when rectal temperatures were at 37 degrees C or above; tumor blood flow increased intratumor temperature gradients by 0.10 degrees C for each 1.5 degrees C that the body temperature was below 37 degrees C. PMID- 3353499 TI - Stable H2O2-resistant variants of Chinese hamster fibroblasts demonstrate increases in catalase activity. AB - Hydrogen peroxide (H2O2)-resistant variants of the Chinese hamster ovary HA-1 line have been derived by culturing cells in progressively higher concentrations of H2O2 (greater than 200 days, in 50-800 microM H2O2). The H2O2-resistant phenotype has been stable for over 60 passages (240 days) following removal from the H2O2 stress. The resistant cells demonstrate both increased capacity to deplete exogenously added H2O2 from the growth medium and increased catalase activity. H2O2 resistance correlates well with catalase activity. An increase in chromosome number occurred in the cells adapted to 200-800 microM H2O2, but increases in aneuploidy and tetraploidy were not necessary for resistance. These results suggest that adaptation to chronic oxidative stress mediated by H2O2 in mammalian cells is accompanied by a stable heritable change in expression of catalase activity. PMID- 3353500 TI - Recovery from effects of heat on DNA synthesis in Chinese hamster ovary cells. AB - The hyperthermic inhibition of cellular DNA synthesis, i.e., reduction in replicon initiation and delay in DNA chain elongation, was previously postulated to be involved in the induction of chromosomal aberrations believed to be largely responsible for killing S-phase cells. Utilizing asynchronous Chinese hamster ovary cells heated for 15 min at 45.5 degrees C, an increase in single-stranded regions in replicating DNA (as measured by BND-cellulose chromatography) persisted in heated cells for as long as replicon initiation was affected. Alkaline sucrose gradient analyses of cells pulse-labeled immediately after heating with [3H]thymidine and subsequently chased at 37 degrees C revealed that these S-phase cells can eventually complete elongation of the replicons in operation at the time of heating, but required about six times as long relative to control cells which completed replicon elongation within 4 h. DNA chain elongation into multicluster-sized molecules was prevented for up to 18 h in these heated cells, resulting in a buildup of cluster-sized molecules (approximately 120-160 S) mainly because of the long-term heat damage to the replicon initiation process. Utilizing bromodeoxyuridine (BrdU)-propidium iodide bivariate analysis on a flow cytometer to measure cell progression, control cells pulsed with BrdU and chased in unlabeled medium progressed through S and G2M with cell division starting after 2 h of chase time. In contrast, the majority of the heated S-phase cells progressed slowly and remained blocked in S phase for about 18 h before cell division was observed after 24 h postheat. Our findings suggest that possible sites for where the chromosomal aberrations may be occurring in heated S-phase cells are either (1) at the persistent single-stranded DNA regions or (2) at the regions between clusters of replicons, because this long-term heat damage to the DNA replication process might lead to many opportunities for abnormal DNA and/or protein exchanges to occur at these two sites. PMID- 3353501 TI - Early structural changes in sheep lung following thoracic irradiation. AB - Using a large animal model of radiation lung injury--the sheep exposed to bilateral thoracic irradiation--we have recently shown the development of sustained pulmonary hypertension during the first 4 weeks following radiation. This is the period prior to the onset of pneumonitis and pulmonary fibrosis. In the present study, we have examined biopsy and autopsy lung tissue from these same sheep and assessed the sequential changes in lung morphology. Six unanesthetized sheep received bilateral thoracic irradiation (a total of 15 Gy); control sheep were sham irradiated. Lung biopsy tissue was taken prior to and at weekly or biweekly intervals during the 4 weeks immediately following radiation. The lungs were also removed at autopsy for light and electron microscopic examination. Our results show early (Week 1) interstitial and progressive intraalveolar edema accompanied by endothelial and epithelial injury. A gradual increase in number of interstitial mononuclear cells was evident from Week 1, both in the lung tissue and in perivascular cuffs. The number of peripheral lung interstitial mononuclear cells was twice baseline from Week 3 and included accumulation of lymphocytes, fibroblasts, and intravascular macrophages. The increased numbers of mononuclear cells paralleled the development of chronic pulmonary hypertension, perhaps suggesting their involvement in the pathogenesis of this disease. Alternatively, it may be that increased mononuclear cell number represents a stage of lung repair. PMID- 3353502 TI - The role of low intracellular or extracellular pH in sensitization to hyperthermia. AB - Cells are more sensitive to heat when they are heated in an acidic environment, and this study confirms (K. G. Hofer and N. F. Mivechi, J. Natl. Cancer Inst., 65, 621, 1980) that intracellular pH (pHi) and not extracellular pH (pHe) is responsible for the sensitization. The relationship between pHe, pHi, and heat survival of cells heated in vitro in various buffers at pHe 6.3-8.0 was investigated. Cells' adaptation to low environmental pH in terms of increases in pHi and heat survival also was investigated. Finally, we studied the relationships among pHe, pHi, and survival from heat for cells heated in sodium free reconstructed medium. Intracellular pH was measured by the distribution of the weak acid, [2-14C]5,5-dimethyl-2,4-oxazolidinedione. Our results are summarized as follows: (1) CHO cells maintained the same relationship between pHe and pHi in four different media or buffers (McCoy's 5a medium buffered with CO2 and NaHCO3 or 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (Hepes) and 2-(N morpholino)ethanesulfonic acid (Mes), Krebs-Ringer bicarbonate solution, and Krebs-Ringer phosphate solution) with pHi being 0.05 to 0.20 pH units higher than pHe as it varied from 7.0 to 6.4; furthermore, heat sensitization by acid was the same in medium buffered with NaHCO3 or Hepes and Mes. (2) The low pHe adapted cells multiplied with an increased doubling time of 20.7 +/- 0.7 h and appeared morphologically similar to the unadapted cells. However, the pHi of these cells was 0.15-0.30 pH units higher than that of the unadapted cells when pHe was varied between 7.0 and 6.3. (3) After being heated at 43.5 degrees C for 55 min or at 42.5 degrees C for 150 min at pHe 6.3-7.2, the pHi of the adapted cells increased by 0.2-0.1 pH units. However, heat caused no significant change in the unadapted cells. (4) Heat survival plotted versus pHe was 1000-fold higher for the adapted cells than for the unadapted cells at pHe of 6.3. However, heat survival plotted versus pHi was identical for the two cell types. (5) In sodium free reconstructed McCoy's 5a medium, pHi was 0.25-0.1 pH units lower than that in the sodium-containing counterpart at pHe 6.3-7.2, and heat sensitization increased accordingly; however, heat survival plotted versus pHi was identical for the two types of media. PMID- 3353503 TI - Induction and repair of DNA strand breaks and 1-beta-D-arabinofuranosylcytosine detectable sites in 40-75 kVp X-irradiated compared to 60Co gamma-irradiated human cell lines. AB - We have compared the initial yield and subsequent enzymatic repair of DNA strand breaks and 1-beta-D-arabinofuranosylcytosine (araC)-detectable sites in cultured human cell lines after irradiation with soft (40-75 kVp) X rays and hard (60Co) gamma rays, two forms of low-LET radiation whose average ionization densities differ by 15-fold (i.e., approximately 4.5 keV/mu and approximately 0.3 keV/mu, respectively). Incubation of X- or gamma-irradiated cell cultures in the presence of araC resulted in the accumulation of DNA single-strand interruptions, as measured by conventional velocity sedimentation analysis in alkaline sucrose gradients. Since the drug is a selective inhibitor of DNA polymerase alpha, this observation implicates polymerase alpha in the repair of radiogenic damage. Specifically, DNA repair analysis in X-ray-treated cells suggested that polymerase alpha is a key participant in the repair of a distinct, albeit structurally undefined, class of radioproducts [presumably a combination of double-strand breaks and alkali-stable lesions (e.g., modified base/sugar residues and DNA crosslinks)], but takes little, if any, part in the restitution of single-strand breaks (whether frank scissions or alkali-labile bonds) induced by ionizing radiation. Accordingly, the drug did not significantly inhibit the repair of DNA damage in cultures exposed to less than or equal to 100 Gy of gamma radiation. A remarkable difference was evident with respect to the absolute yields of these two major classes of DNA injury--that is, araC-detectable sites and single-strand breaks--depending on the type of radiation administered. For the same dose, the level of araC-detectable sites found in cells treated with gamma rays (less than or equal to 150 Gy) was as much as 3.4 times lower than that observed in X-ray-exposed cells (i.e., one site per 1,155 and 335 eV, respectively). In contrast, the number of strand breaks induced by gamma rays was approximately 2.3-fold higher than that produced by X rays (one break per 27 and 61 eV, respectively). Assuming that, among other conditions, the relative biological effectiveness of the comparatively densely ionizing soft X rays is roughly twice that of the sparsely ionizing hard gamma rays, our data strongly imply that those radioproducts which are manifested as araC-detectable sites may be approximately 45 times more deleterious, on a per lesion basis, than those observed as single-strand breaks. PMID- 3353504 TI - Effects of sodium butyrate and 3-aminobenzamide on survival of Chinese hamster HA 1 cells after X irradiation. AB - HA-1 cells were grown in medium containing 2 mM sodium butyrate and then exposed to graded doses of 250 kVp X rays. After irradiation, some of the butyrate treated cultures were treated with either 10 or 20 mM 3-aminobenzamide for 2 h at 37 degrees C. The butyrate treatment produced a small degree of radiation sensitization as indicated by an increase in the alpha parameter using a linear quadratic description of survival responses. The dose-modifying factor at the 10% survival level (DMF10) was 1.15. Similarly, both 10 and 20 mM 3-aminobenzamide treatments produced concentration-dependent increases in radiosensitization, again as indicated by an increase in the value of the alpha constant, with DMF10 values of 1.22 and 1.40, respectively. However, the combination of the 2 mM sodium butyrate + 10 mM 3-aminobenzamide treatments produced a supraadditive response in terms of increased cell killing (DMF10 = 1.76). We interpret this to mean that 3-aminobenzamide inhibits a sodium butyrate associated increase in poly(ADP-ribose) which then predisposes hyperacetylated chromatin to attack by endogenous nucleases leading to increased cytotoxicity. PMID- 3353506 TI - Multidisciplinary contributions of the journal. PMID- 3353505 TI - Comments on strand breaks calculated from average doses to the DNA from incorporated isotopes. AB - The techniques used to calculate DNA strand breakage from average doses to small segments of DNA are examined. It is shown that the methods of calculation contain serious flaws and lead to invalid results. PMID- 3353507 TI - Implication of prostaglandins and histamine H1 and H2 receptors in radiation induced temperature responses of rats. AB - Exposure of rats to 1-15 Gy gamma radiation (60Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations. PMID- 3353508 TI - Radioemetic protection at 24 h after 60Co irradiation in both normal and postremectomized cats. AB - The radioemetic dose-response relationships were established in 46 unanesthetized cats for each of two whole-body exposures, 24 h apart, to 60Co radiation at selected doses between 7.5 and 60 Gy. Individual episodes of vomiting were recorded for a period of 48 h as distinctive intrathoracic pressure deflections signaled through a catheter placed in the superior vena cava. Five cats with chronic lesions of the area postrema were included in the group exposed to 45 Gy. The lesioned animals were not detectably different in their radiation response behavior from the intact cats. Initial exposure in the entire cat series produced an increasing incidence of radioemesis from 25 to 80% over the specified dose range for the first observation period of 24 h. By contrast, the second exposure produced an inverse dose-related incidence of emesis varying from 63% to zero with an apparent crossover of radioemetic susceptibility for the two exposures at about 15 Gy. Complete protection during 12 h after the second exposure was obtained at 30, 45, and 60 Gy, and for all of 24 h at 45 and 60 Gy. In a separate group of 11 normal cats, the emetic drug xylazine invariably evoked vomiting when radioemetic protection was otherwise manifest after initial irradiation at 45 Gy. We conclude that the temporary recovery of well-being following acute lethal irradiation results selectively through increased radioemetic resistance, and it does not depend on the integrity of the area postrema. PMID- 3353509 TI - Further studies on the radiation-induced expression of a tumor-specific antigen in human cell hybrids. AB - The neoplastic transformation of human cell hybrids (HeLa x skin fibroblasts) is accompanied by the expression of a cell surface protein for which monoclonal antibodies have been raised. The gamma-radiation-induced neoplastic transformation of these cells has been studied where the expression of this cell surface protein, as detected by immunoperoxidase staining, has been used as an end point. The yield of foci of positively staining cells has been shown to increase with increasing time postirradiation at which the assay is done and decrease with increasing density of viable cells plated postirradiation. The time of plating postirradiation is also an important parameter with transformation frequencies increasing over the first 6 h of postirradiation holding at confluence, followed by a gradual decrease. PMID- 3353510 TI - Postirradiation alterations of neuronal chromatin structure. AB - Previous work from our laboratory suggested that neuronal chromatin structure may be altered immediately after exposure to ionizing radiation. In the present study, whole brains of 4-month-old male Fisher 344 rats were irradiated with a dose of 25 Gy. The kinetics of restoring the chromatin structure to its unirradiated state was investigated in rat cerebellar neurons using three different approaches: (1) measurement of changes in the DNA superhelical structure by the fluorescent halo assay, (2) measurement of changes in chromatin accessibility to digestion by micrococcal nuclease, and (3) measurement of changes in the accessibility of the nuclear-matrix-associated DNA to digestion by DNase I. Immediately after irradiation, the topological constraints on the DNA loops were altered, the chromatin was more accessible to m. nuclease digestion, and the DNA associated with the nuclear matrix was more resistant to digestion by DNase I. Return of the chromatin structure to its unirradiated state as measured by each of the three methods followed biphasic kinetics with the fast phase having a half-time of several minutes and the slow phase having a half-time of several hours. The kinetics are similar to that previously reported for repair of radiation-induced DNA damage in mammalian cells. Although the independent assays used in this study seemed to follow the same kinetics, their relationship at the molecular level remains to be determined. PMID- 3353511 TI - [Psychoanalysis at an institution]. PMID- 3353512 TI - ["Amadeus"--some reflections on envy]. PMID- 3353514 TI - [Some comments on Freud's repudiation of the seduction theory]. PMID- 3353513 TI - [The psychoanalyst as an interpretive conversational participant]. PMID- 3353515 TI - Enhanced preference for a flavour following reversed flavour-glucose pairing. PMID- 3353516 TI - Thoracic CT-scanning follow-up of residual mediastinal masses after treatment of Hodgkin's disease. AB - Sequential thoracic CT-scanning was performed for 14 patients presenting with residual mediastinal masses on chest X-ray after treatment of stage I and II Hodgkin's disease (HD). Eleven patients initially presented with bulky mediastinal involvement. No mediastinal biopsy was performed. No local recurrence was detected at a 48 month median follow-up. Early evaluation by CT-scanning showed cystic degeneration in three cases. Sequential CT-scans on longer follow up demonstrated continuous regression of residual masses in six cases and no or limited volume reduction in six other cases. In two patients, part of the residual mass remained stable and the other part showed reduction in size. In addition, late calcifications developed in four cases. The results of sequential CT-scanning suggest that residual mediastinal masses do not generally represent active disease. Hence additional, potentially toxic, therapy can be avoided. PMID- 3353518 TI - Effect of step-down heating on hyperthermic radiosensitization in an experimental tumor and a normal tissue in vivo. AB - The effect of step-down heating (SDH) on the radiosensitization induced by simultaneous hyperthermia and radiation was investigated in a C3H mammary carcinoma inoculated into the feet of CDF1 mice and the skin of normal CDF1 feet. SDH consisted of a sensitizing treatment (ST) of 44.5 degrees C/10 min followed by a test treatment (TT) of 41.5 degrees C for 30, 60 or 120 min. Simultaneous administration of radiation and hyperthermia was achieved by delivering radiation in the middle of the TT. The endpoint selected was the radiation dose needed to achieve either tumor control or moist desquamation in 50% of the animals. The results were evaluated by the thermal enhancement ratio (TER), defined as dose of radiation needed to achieve endpoint in relation to dose of combined radiation and hyperthermia needed to achieve the endpoint. SDH of tumors increased the TER significantly compared with step-up heating (SUH). The ratios between TCD50 values for corresponding SDH and SUH increased with TT heating time and at 120 min a 2.5-fold increase in the radiosensitizing effect was achieved. It has previously been shown that SDH alone causes thermosensitization in tumors by decreasing the activation energy. However, the effect was too small to explain the increased radiosensitization observed with SDH. In the normal tissue studies SDH combined with radiation treatment gave a lower TER compared to the SDH tumor results, suggesting a possible therapeutic gain. PMID- 3353517 TI - Sequential combination of 5-fluorouracil, cis-platinum and irradiation. 1. Advanced head and neck cancers. AB - Based on the synergistic action of 5-fluorouracil (5-FUra), cis dichlorodiamminoplatinum(II) (cis-DDP) and gamma-rays, which was suggested in experiments on murine tumours, a sequential treatment combining irradiation and chemotherapy for human solid tumours known to be resistant to conventional treatments has been developed. A pilot study was carried out on 30 patients with recurring head and neck cancers previously treated by radiotherapy and surgery. The good tolerance and the initial results justified applying this protocol to previously untreated cases. The second study involved 40 patients with stage III and IV tumours. After 3 cycles of combined radio- and chemotherapy followed by a conventional radiotherapy, 78% were good responders (51% in complete remission). Oropharynx and oral cavity, without base of tongue, have a 51% actuarial survival at 3 years when they achieved an early complete remission. PMID- 3353519 TI - Re-irradiation of mouse skin: similarity of dose reductions for healing and macrocolony endpoints. AB - The amount of residual injury in mouse tail skin, assessed by the decrease in re irradiation dose for equal effect, was similar whether assessed using healing or colony endpoints (17-21% after single priming doses). There were tendencies towards an increased sensitivity of the colony-forming cells by a factor of about 2, and less residual injury after multifractionated priming doses. These observations are compatible with a lower alpha/beta ratio characterising the response to dose fractionation for residual injury than for the acute healing response. PMID- 3353521 TI - Quantitative measurement of changes in human lung density following irradiation. AB - In a recent clinical study, we have shown that computed tomography (CT) can provide a good qualitative endpoint for the presence of radiation-induced pulmonary damage. However, CT data are also potentially useful as a quantitative measure of lung damage. Changes in lung density were quantified by comparing CT images taken before and after radiotherapy for 54 patients. Lung densities were assessed separately in the irradiated and nonirradiated regions using both the average regional densities and density distributions. For the 36 patients demonstrating visible post-irradiation lung damage on CT, the mean relative increase in average lung density was 0.20 +/- 0.10 in the irradiated regions. The mean change in the nonirradiated regions was 0.02 +/- 0.09 for the same group. For 18 patients without visible damage, the mean relative changes were 0.00 +/- 0.09 and -0.05 +/- 0.07 for the irradiated and nonirradiated regions, respectively. The results suggest that an increase in average lung density of 5% or greater is associated with the visible detection of pulmonary damage. The dose response relationship based on this quantitative criterion was comparable to that derived using the qualitative endpoint. PMID- 3353520 TI - Interstitial hyperthermia using 27 MHz wire antennas and interstitial photodynamic therapy in a rat rhabdomyosarcoma: phantom and animal studies. AB - This paper deals with the interaction of interstitial hyperthermia (HT) and interstitial photodynamic therapy (PDT). Its main focus, however, is on a newly developed heating system; phantom studies as well as temperature-response data obtained from the in vivo experiments are presented. Heat was delivered by thin, flexible wire antennas operating at a frequency of 27 MHz. Measurements in muscle equivalent phantom with infrared thermography were performed. Uniform heating over the inserted length of the antenna was obtained and impedance matching appears possible by simple variable air coils, thereby minimizing the reflected power to less than 20%. Light was obtained from an Argon-Dye laser system tuned to a wavelength of 625 nm at a dose rate of 75-100 mW per fiber to a total incident dose of 900 J from four linear light applicators. An experimental murine tumor (Rhabdomyosarcoma, type R-1) was transplanted in WAG/Rij rats and, after reaching an average diameter of 2 cm, the active component of haematoporphyrin derivative (HPD), Photofrin II, was injected intravenously. The tumors were subsequently implanted with four flexible catheters, through which either light or heat could be applied. Dose-response relationships for PDT alone, HT alone and PDT followed by HT were established with cure as endpoint. The animal experiments showed that with the use of low-frequency wires a good localized heat distribution in the tumors can be obtained. Moreover, this study showed that PDT and HT, in the proper sequence and only when optimal temperatures are reached, result in an augmented cytotoxicity on the tumor cells in vivo; i.e. a cure rate of 41% was obtained. PMID- 3353522 TI - Accuracy in radiation field alignment in head and neck cancer: a prospective study. AB - A prospective study has been performed to determine the accuracy of radiation field alignment for a group of 22 patients with tumors in the head and neck. The accuracy was assessed by an analysis of 138 megavolt portal films in comparison to 55 simulation films. The distance (at the patient midplane) between corresponding points at the field edges on verification film and simulation film appeared to be 5 mm on the average and the standard deviation 5 mm. The analysis was extended by translational and rotational matching of the fields in order to separate each error in a translation error of the field with respect to the patient and an error in field size or shape. Translation errors appear to be somewhat larger than field size or shape errors. From an analysis of a series of megavolt films taken every third radiotherapy session, it was concluded that treatment-to-treatment variations are as large as the errors due to the transition from simulation to treatment situation. Further analysis showed that variation of the patient's position within the cast is clearly one of the error sources. PMID- 3353524 TI - [Comparison of bupivacaine hydrochloride 0.5% and bupivacaine carbonate 0.5% in interscalene plexus anesthesia]. AB - Carbonated local anesthetics are less acidic than the hydrochlorides and require less buffering by the tissues. Rapid buffering and diffusion of the carbon dioxide enables free base to be deposited in high concentrations on nerve fibres. Carbon dioxide increases the intracellular hydrogen ion concentration, thus increasing the amount of active cation at the receptor site. The interscalene approach to the brachial plexus was chosen for comparison of bupivacaine hydrochloride 0.5% and carbonated bupivacaine 0.5%. The interscalene route has many potential advantages, including anesthesia of the shoulder and reliable block of the musculocutaneous nerve, but large volumes of local anesthetic solutions are needed. The use of such volumes may exceed the limit of toxicity. Therefore, the plasma concentrations produced by 40 ml of local anesthetic solution were studied in 42 patients for whom brachial plexus block was considered a suitable technique. The latency of onset of sensory analgesia was shortest and with the least variability in the dermatomes C5-C7. The first analgesia was detected by pinprick 5.1 +/- 0.4 (SE) min and complete analgesia in 19 +/- 1 min after bupivacaine hydrochloride and 4.7 +/- 0.5 min and 15 +/- 1 min after bupivacaine carbonate. The more caudad nerves showed a significantly longer latency time than the more cephalad ones. The duration of sensory analgesia varied between 6 and 12 hours, the more caudad nerves showing the shortest duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353525 TI - [The effect of thoracic peridural analgesia on the cortisol and glucose response in surgery of the abdominal aorta]. AB - It has been shown that the stress response to lower abdominal surgery can be inhibited by epidural analgesia (EA). But EA seems to have little influence on the stress reaction to major abdominal surgery. The purpose of our study was to find out whether EA is able to diminish the cortisol and glucose response to major transabdominal surgery. METHODS: 31 patients undergoing elective surgery of the abdominal aorta were subdivided at random into 3 different anaesthesia groups: 1. halothane anesthesia, 2. neuroleptanalgesia (NLA) and 3. thoracic EA with bupivacaine (0.5%) in combination with a light general anesthesia. Some patients of each group received an intravenous infusion of 5% glucose. Blood samples were drawn before anesthesia, after intubation, 5 times during surgery and at the end of the operation and were analysed for cortisol and glucose. During the early postoperative period, 1, 2 and 24 h after surgery, only cortisol was measured. RESULTS: Only the glucose levels of patients who received no carbohydrate-containing infusion fluids were used for evaluation of the stress response. In the halothane group, there was a significant increase of the mean cortisol and glucose levels after the start of surgery. No intraoperative elevations of blood glucose and cortisol were seen in the EA group. Patients of the NLA group showed no hyperglycaemia and only mild elevations of the cortisol levels during the intraoperative period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353523 TI - Stimulating effect of pentagastrin on cancer cell proliferation kinetics in chemically induced colon cancer in rats. AB - Pharmacological doses of pentagastrin or gastrin are known to stimulate cell proliferation in normal colonic epithelium but the growth-promoting effect of gastrin on colon carcinoma is still controversial. In this study morphological parameters were measured to study the effect of pentagastrin (240 micrograms/kg) on the cell proliferation kinetics in experimental tumours. Colon cancer was produced in rats by weekly injections (20 mg/kg b.wt.) of 1.2-dimethylhydrazine for 24 weeks. Tritiated thymidine was given after administration of pentagastrin or the control solution to the animals. 75% of the animals from the pentagastrin group and 66% of the controls had at least one colon cancer. Autoradiographs of the colonic tumors were performed and the percentage of labeled cells in the cancer cell population was determined after counting 4000 to 16,000 cancer cells per tumor. The labeling index for cancer cells in the pentagastrin-treated group (21.49 +/- 1.76%) was higher (P less than 0.01) than in the control group (14.76 +/- 0.66%). In a second study vincristine sulphate (1 mg/kg) was given to the animals 20 h after administering pentagastrin or the control solution. The percentage of arrested metaphases in the tumours was determined after counting 10,000 to 24,000 cancer cells per histological section. Pentagastrin increased (P less than 0.01) the mean metaphase index by 108% (4.9 +/- 0.44% vs 2.35 +/- 0.32%). These data indicate that cell cycle manipulation of colon cancer is possible with hormonal peptides. PMID- 3353527 TI - [Anesthesiologic management of cesarean section in a patient with transposition of the great vessels]. AB - The maternal mortality associated with cesarean section in the presence of congenital cyanotic heart disease is high. We report the anesthetic management of a 26-year-old pregnant patient with transposition of the great vessels and a functional single ventricle whose child was delivered by elective cesarean section under continuous epidural anesthesia. There were no hemodynamic problems and the outcome was successful for both mother and child, who could be discharged from the hospital on the 17th postoperative day. Elective cesarean section may be an acceptable method of delivery, and lumbar epidural block proved to be an appropriate procedure for this patient. The cooperation of cardiologists, anesthesiologists, and obstetricians was necessary to assure maternal and fetal survival. Continuous invasive hemodynamic monitoring and use of small epidural top-up doses (2-3 ml) of local anesthetic were of utmost importance in maintaining the hemodynamic stability. PMID- 3353526 TI - [Epidural hematoma following epidural catheter anesthesia in thrombocytopenia]. AB - We report a 21-year-old male patient suffering from acute myeloid leukemia and concomitant thrombocytopenia. Following a diagnostic thoracotomy-which revealed Aspergillus pneumonia-he developed respiratory insufficiency and dyspnea. A thoracic epidural catheter was inserted and epidural morphine treatment led to improved ventilation. No clinical signs of pathological epidural processes were noticed during the treatment. The patient died of Aspergillus sepsis 26 days after catheter insertion. Autopsy revealed bacterial growth in the epidural space with slight infectious tissue reactions as well as an epidural hematoma. No evidence of spinal cord compression was found at autopsy. The development of epidural infection or hematoma seems to be a possible complication of epidural analgesia in patients suffering from impaired defense mechanisms or thrombocytopenia. These risk factors should be taken into account when epidural analgesia is considered. We suggest that the platelet count should be determined beforehand in patients suspected of having thrombocytopenia (e.g. cancer, pre eclampsia). PMID- 3353528 TI - [Inguinal paravascular blockade (3-in-1 block) in combination with general anesthesia]. PMID- 3353529 TI - [Axillary blockade of the brachial plexus. A prospective evaluation of 1133 cases of plexus catheter anesthesia]. AB - The results of 1133 axillary catheter brachial blocks are reported. Effectiveness and side-effects were monitored in a prospective manner over a period of 1 year. METHOD: The puncture was performed with an 18-gauge plastic cannula fitted with a solid steel stylet. The stylet has a 45 degrees, short bevel with rounded edges. When puncturing the axillary neurovascular sheath, no attempt was made to elicit paresthesias with the needle. A distinct "click" and very easy advancement of the plastic cannula were signs of being well inside the neurovascular sheath. To confirm the correct positioning, 0.5-3 ml refrigerated saline solution were injected. If no paresthesias could be produced, a new puncture was performed using a nerve stimulator. The plastic cannula was fixed to the skin. For long lasting operations or if postoperative analgesia or sympatholysis was required, a more flexible catheter was introduced through the plastic cannula. As an initial dose 40 ml 1% mepivacaine was injected via the cannula. If there was an insufficient block after 20 min, another 20 ml 1% mepivacaine was given. For long lasting operations, 40 ml 1% mepivacaine was injected every 2 h. RESULTS: Surgery was completed in 72% of patients; 24% required some form of supplementation including 17.2% of patients who received a "top-up" after 20 min (Table 1). In 3.8% of cases the technique was considered to be a complete failure, meaning that patients needed some type of general anesthesia including the use of i.v. ketamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353530 TI - The technical quality of mammography in centers participating in a regional breast cancer awareness program. AB - Quality control is particularly critical in mammography. Data presented here suggest that even among centers established for breast cancer detection, there is need for improvement. PMID- 3353531 TI - Gd DTPA. Clinical efficacy. AB - Both the diagnostic accuracy and sensitivity of the MRI diagnosis of central nervous system neoplasms appear to be improved by the administration of a paramagnetic contrast agent, Gd DTPA. PMID- 3353532 TI - Gd DTPA. Future applications with advanced imaging techniques. AB - In this admittedly preliminary view of the future, the authors present a number of new concepts in MR imaging and consider their possible advantages and limitations. PMID- 3353533 TI - Pediatric case of the day. Osteoblastoma of the lateral mass of C6 on the right. PMID- 3353534 TI - High resolution CT of the lung parenchyma with pathologic correlation. AB - The authors describe a technique for directly correlating high resolution CT scans and gross and histologic sections of the lung. They conclude that HRCT provides anatomic detail comparable to that seen on gross tissue inspection. PMID- 3353535 TI - The Radiological Society of North America. 73rd scientific assembly an d annual meeting. Image interpretation session. Sunday, November 29, 1987. PMID- 3353536 TI - Magnetic resonance imaging of internal derangements of the knee. AB - The authors, in a careful prospective study, report the accuracy of MRI to be comparable to that of pneumoarthrography and arthroscopy in the diagnosis of internal derangements of the knee. PMID- 3353537 TI - Cognitive assessment and intervention: Captain's Log. PMID- 3353538 TI - MusicShapes. PMID- 3353539 TI - Problem behavior and psychiatric impairment within a developmentally disabled population. III: Psychotropic medication. AB - This report is the third in a series on problem behavior and psychiatric impairment in a population of 35,000 individuals receiving developmental disabilities services. Young and middle-aged adults were found to receive psychotropic medication at higher rates than children, adolescents, or elderly persons. Psychotropic receipt rates were found to increase with increasing severity of mental retardation, but most evidently with increasing restrictiveness of residential setting, increasing rated severity of problem behaviors, and presence of a psychiatric impairment. Rates of medication receipt also varied as a function of psychiatric diagnostic category. Discussion remarks emphasize the need to include information relative to clinical and social aspects of program settings and the roles and decision-making performance of physicians and psychologists in research on settings serving persons with developmental disabilities. PMID- 3353541 TI - Depression in mentally retarded children. AB - Thirty-one mentally retarded emotionally disturbed children, hospitalized within a university medical school's psychiatric intensive care program, were matched on age and sex and compared to 31 children from a normal school setting on depression. Measures included the Child Depression Inventory (CDI) and the Child Behavior Profile (CBP), with children being compared on total and subfactor scores for both measures. Depression and its various subcomponents were more prevalent in the mentally retarded group. There were no significant sex or age differences. Degree of overall psychopathology and depression were highly related. The relationship between criteria for depression on the CDI and CBC were also made. Correlational data showed a strong relationship between the cut-off scores for both measures, an important finding because they were based on norms established with children of normal intelligence. These data suggest that similarities exist between depression in mentally retarded children and those without such cognitive handicaps. The relationship of depression to other forms of psychopathology in the group of 31 emotionally disturbed mentally retarded children was also examined. A wide range of disorders including schizophrenia, aggression, withdrawal, and hyperactivity were evaluated. These are the first empirical data with mentally retarded children in the United States that are aimed specifically at evaluating depression, and should be useful to the clinicians in better understanding the phenomenon. PMID- 3353540 TI - Community-based instruction with profoundly mentally retarded persons: client and public responsiveness. AB - Three experiments were conducted to evaluate the effects of a training program implemented in a community setting for teaching receptive language skills to profoundly mentally retarded persons. In Experiment 1, the program was implemented in a local department store and consisted of a least-to-most intrusive prompting paradigm and contingent consequences. The community-based training strategy was effective in teaching receptive identification of three objects to a profoundly mentally retarded adolescent. Additionally, generalized improvements occurred in other store locations, although cross-modal generalization in terms of changes in expressive skills did not occur. These results were replicated in Experiment 2 with two other clients in the same store, and in Experiment 3 with another client in an outdoor recreational area. Also, a questionnaire survey indicated that store employees in the first two experiments had very favorable reactions to the program. Results are discussed in regard to continued research with community-based training as a means of expanding educational opportunities for individuals who are profoundly mentally retarded. PMID- 3353542 TI - Ongoing use of an affective rating scale in the treatment of a mentally retarded individual with a rapid-cycling bipolar affective disorder. AB - Empirically tracking cyclic variations in the behavior of mentally retarded individuals with bipolar affective disorders is difficult because disturbances in mood are difficult to operationally define and quantify. The following report presents a case study in which a moderately retarded man's mood and energy were rated by direct care staff who completed a mood rating scale two times each day. The resulting weekly summaries of the data were plotted on a graph which indicated the cyclic fluctuations in symptom areas related to his bipolar disorder. This information was of great value in assessing therapeutic interventions and in designing habilitative activities congruent with shifts in the behavioral patterns. PMID- 3353543 TI - Reducing inappropriate behaviors of developmentally disabled adults using antecedent aerobic dance exercises. AB - The effects of aerobic dance exercise on inappropriate behaviors of two developmentally disabled adults were observed in a day activities center. The experimental phase, in which the subjects engaged in exercise with seven other individuals on Monday, Wednesday, and Friday of each week, was preceded and followed by baseline phases in which subjects did not exercise and in which there were no contingencies in effect for the dependent variables. Exercises consisted of those commonly used in exercise dance classes. Observations occurred during 15 minute periods immediately before and following exercise while subjects engaged in regular classroom activities. Observations also occurred in the same time periods on no-exercise days during all phases. Behaviors observed included inappropriate vocalizations, repetitive movements, and off-task. Results indicate for both subjects a decrease in each of the inappropriate behaviors as a result of exercise. PMID- 3353544 TI - Measuring knowledge of citizenship rights and responsibilities. AB - The purpose of this study was to develop and standardize an instrument designed to assess the extent to which people with mental retardation demonstrate knowledge about citizenship rights and responsibilities. The test development phase included: (a) generating 83 items related to six content areas (i.e., human, civil, and legal rights; and moral, civic, and legal responsibilities), and (b) pilot testing these items with 236 members of self-advocacy groups for people with developmental disabilities. The resulting 30-item instrument was standardized with a sample of 391 self-advocates from 13 states. The psychometric properties of the standardized instrument included: a mean performance level of 77% correct; a mean item-total correlation of r-ij = .33; and an internal consistency reliability coefficient of r alpha = .82. The instrument's potential usefulness as a device for screening, diagnosis, and program evaluation was supported by its psychometric properties. Future studies could address the use of the instrument with the secondary school age population that faces the transition from school to community. PMID- 3353545 TI - [Effect of epidural bupivacaine on platelet aggregation and bleeding time]. PMID- 3353546 TI - [Hemoglobin desaturation during orotracheal aspiration]. PMID- 3353547 TI - [The intracavitary electrocardiogram for checking catheters in the right atrium]. PMID- 3353548 TI - [Use of butorphanol in peridural anesthesia: a preliminary report]. PMID- 3353549 TI - [Conventional ventilation via transtracheal catheter. A gasometric study and its potential use]. PMID- 3353550 TI - [Sedation in tetanus]. PMID- 3353551 TI - [Therapeutic regimen in the medical treatment of cancer pain]. PMID- 3353552 TI - [Postoperative care in severe lesions of the upper extremity]. PMID- 3353553 TI - [Septic meningitis following intradural anesthesia]. PMID- 3353554 TI - [Tumors of the anterior mediastinum. Apropos of a case]. PMID- 3353555 TI - [Cardiac herniation following radical intrapericardial pneumonectomy]. PMID- 3353558 TI - [The Revista Espanola de Cardiologia in 1988: its monthly publication]. PMID- 3353556 TI - [Bicompartmental location of a multiorifice peridural catheter]. PMID- 3353557 TI - [Comments on the Boyle 2000 Modular]. PMID- 3353559 TI - [Evaluation of congenital aortic stenosis by noninvasive methods]. PMID- 3353560 TI - [Hemodynamic effects of intravenous verapamil in patients with obstructive myocardiopathy]. PMID- 3353561 TI - [Perioperative mortality risk in coronary revascularization surgery: a prospective study on 130 patients]. PMID- 3353562 TI - [Surgery of interatrial communication in the adult. Long-term results in 100 consecutive cases]. PMID- 3353563 TI - [Registry of patients with acute myocardial infarct and unstable angina hospitalized in Barcelona (I). The demand for care]. PMID- 3353564 TI - [Effect of various doses of aspirin on the development of aseptic thrombotic aortic endocarditis experimentally induced in the rabbit]. PMID- 3353565 TI - [Aneurysm of the interatrial septum in a 13-month-old girl with interatrial communication]. PMID- 3353566 TI - [Echocardiographic diagnosis of an aneurysm of the interatrial septum associated with mitral valve prolapse]. PMID- 3353567 TI - [Therapeutic embolization via catheterization of a Blalock-Taussig fistula]. PMID- 3353568 TI - Integrating program evaluation, quality assurance, and marketing for inpatient rehabilitation. PMID- 3353569 TI - Head trauma rehabilitation: program evaluation. PMID- 3353571 TI - A patient satisfaction survey for a rehabilitation unit. PMID- 3353570 TI - Unit-level quality assurance: essential for success. PMID- 3353573 TI - Nurses' use of the terms compliance and non-compliance in rehabilitation nursing practice. PMID- 3353572 TI - Lifestyle behaviors in treated hypertensives as prediction of blood pressure control. PMID- 3353574 TI - [3d seminar on the nutrition and feeding of herbivores. Paris, 26-27, March 1987. Proceedings]. PMID- 3353575 TI - Homocysteine thiolactone in arteriosclerosis and cancer. AB - Homocysteine thiolactone was isolated from normal human plasma, sera of patients with acute myocardial infarction, and human neoplastic tissue. The compound was identified by ninhydrin reaction and by nitroprusside reaction following alkaline hydrolysis. Thin layer and ion exchange chromatography demonstrated a single uniform peak which co-chromatographed with authentic homocysteine thiolactone. The substance was isolated by extraction of plasma, serum or tissue with chloroform:methanol, re-extraction of the chloroform layer with dilue HCl, and evaporation of the resulting aqueous acid layer. The amount of homocysteine thiolactone was found to be 1,670 mumol/L in normal human serum and 12,500 mumol/L in sera of coronary heart disease patients. Although there is variability and overlap of values between groups, the difference between the two groups is significant (P = 0.025). The amount of homocysteine thiolactone in three human neoplasms was 17-123 mumol/kg. Only trace amounts were found in normal tissues, and none was detected in two other human neoplasms. The findings support the previous demonstration of abnormal homocysteine thiolactone metabolism in arteriosclerosis and cancer. PMID- 3353576 TI - Pyruvic acid protects against the lethality of sulfide. AB - The efficacy of pyruvic acid in protecting mice against the lethal effects of sodium sulfide was examined. Pyruvic acid (1 g/kg, i.p.) reduced the mortality of sodium sulfide (100 mg/kg, i.p.) from 100% to 5% when administered 15 min prior to the sulfide. The protective effect of pyruvic acid decreased over time but was still present at 20 min and 30 min, with 40% and 50% mortality, respectively. The lethality of sulfide in larger mice was less than that in smaller mice when the doses were normalized for body weight, but the protection factor of the pyruvic acid, approximately 2.0, was the same for both sizes. PMID- 3353577 TI - Reduction of doxorubicin-induced cardiotoxicity in mice by taurine. AB - The effect of taurine on doxorubicin-induced cardiotoxicity was examined in mice. A single intraperitoneal injection of doxorubicin (15 mg/kg) produced a significant elevation of calcium and lipoperoxide content at 72 hr, as well as a significant depletion of creatine phosphokinase, glutamic oxaloacetic transaminase and lactate dehydrogenase activities at 48 hr and glutathione peroxidase activity at 24 hr in the myocardium. These results suggest that a substantial myocardial damage had occurred. All biochemical alterations except depletion of glutathione peroxidase, were markedly attenuated by the combined oral and intraperitoneal administration of taurine. Taurine significantly improved the survival rate of the mice treated with doxorubicin. These results demonstrate that taurine antagonized doxorubicin-induced cardiotoxicity. PMID- 3353578 TI - The effects of indomethacin on the systemic and regional vasodilator responses to minoxidil in the conscious dog. AB - To define the role of endogenous prostaglandin (PG) synthesis in the vasodilator response to minoxidil (MNX), whole body and regional hemodynamics were measured in conscious, MNX-pretreated dogs before and after the administration of the cyclooxygenase inhibitor indomethacin (INDO). Twenty minutes after an i.v. dose of 2.0 mg/kg, INDO did not affect the reductions in mean arterial pressure and total peripheral resistance achieved with 1.0 mg/kg of MNX i.v. INDO appeared to selectively reverse MNX's vasodilation in the skin and stomach, as vascular resistance in these two tissues increased to pre-MNX levels. Since INDO also exerts a selective vasoconstriction in the skin and stomach of conscious, nonpretreated dogs (Humphrey and Zins, 1983), the fact that skin and stomach resistances were near baseline with this drug combination implies that MNX continues to exert a net vasodilation in these vascular beds. In contrast to INDO's negligible hemodynamic interactions, MNX's vasodilation was nearly completely reversed by continuous i.v. infusions of the direct vasoconstrictor arginine vasopressin (ADH) administered at a mean dose of 35 mU/kg/min. MNX's reversal by ADH was not matched by maximally effective i.v. infusions of the alpha-adrenergic agonist norepinephrine at a mean dose of 0.4 micrograms/kg/min. These results indicate that the sustained peripheral vasodilation seen with MNX in the conscious dog is not dependent upon the synthesis of endogenous, PG-like dilator substances, as defined by concomitant INDO administration. PMID- 3353579 TI - Monthly variations in the pharmacokinetics of antipyrine in the rat: circannual rhythm or random variation? AB - We examined the pharmacokinetics of antipyrine in the rat over an 18 month period to determine whether or not the variations in pharmacokinetic parameters previously reported exhibited a circannual rhythm. While the clearance of antipyrine varied over the study period, no discernible rhythmic pattern was found. Comparing this data with previously published work also failed to demonstrate a rhythmic pattern of variability. Unlike previous investigations, we found only relatively small variations in antipyrine volume of distribution and half-life from month to month. These data indicate that the monthly variability in the pharmacokinetics of antipyrine in the rat are random and do not exhibit a circannual rhythm. PMID- 3353581 TI - Influence of calcium on aluminum accumulation by the rat jejunal slice. AB - The isolated rat jejunal slice was used to determine if aluminum (Al) interacts with the gastrointestinal (GI) calcium (Ca) transporting system. Al uptake by the rat jejunal slice was reduced by Ca channel blockers (verapamil, nifedipine, diltiazem-10 microM) and a medium containing no added Ca. Conversely, Al uptake was increased by Ca channel activators (4-aminopyridine, .05mM, .1mM; Bay k 8644, 1, 10 microM) and by 5mM Ca. Al uptake was saturable and energy dependent but yielded a low activation energy (Ea = 3.9 +/- 0.3 kcal/mole). Al uptake was increased by vanadate (100 microM), an inhibitor of both the active Ca pump and Na/K-ATPase. These results suggest that Al does interact with the GI Ca transporting system. This interaction may form the basis for its accumulation and toxicity in different tissues which contain similar processes for handling Ca. PMID- 3353580 TI - Hepatic lipid peroxidation in CoCl2-treated rats, evidenced by elevated concentrations of thiobarbituric acid chromogens. AB - Parenteral administration of cobalt chloride (CoCl2) to male Fischer-344 rats caused hepatic lipid peroxidation, as evidenced by the thiobarbituric acid (TBA) reaction for malondialdehyde (MDA) and related chromogens in fresh liver homogenates. After a single sc injection of CoCl2 (300 mumol/kg, body wt.), hepatic concentrations of TBA-chromogens became significantly increased by 4 h and reached peak levels at 24-72 h post-injection. For example, in rats killed 48 h post-injection, hepatic TBA-chromogens (mean +/- SD, N = 7) averaged 607 +/- 141 nmol/g of tissue, wet wt., (P less than 0.01 versus 245 +/- 73 nmol/g in 19 controls). A dose-effect relationship was observed between CoCl2 dosages (100 to 450 mumol/kg, body wt.) and hepatic concentrations of TBA-chromogens in rats killed 24 h post-injection. This study indicates that hepatic lipid peroxidation develops as a consequence of acute CoCl2 toxicity in rats. PMID- 3353583 TI - Intestinal ammonium production in the rat: the role of the colon, small intestine, and circulating glutamine. AB - The intestinal ammonium production and the intestinal uptake of circulating glutamine were investigated in anesthetized intact rats and rats with resected small intestine or colon by simultaneous measurements performed on portal and arterial blood. It was shown that ammonium release into the portal blood by the small intestine is of equal magnitude to that released by the colon, and that circulating glutamine participates in ammonium production by the small intestine. Increased levels of circulating glutamine induced by its i.v. infusion to intact rats were not accompanied by an increase in intestinal ammonium production. PMID- 3353582 TI - Accumulation of aluminum by rabbit renal cortex. AB - Aluminum is a ubiquitous metal with significant toxic potential for humans. It is eliminated principally by the kidney, however the mechanisms involved remain obscure. The purpose of this study was to define and quantify the uptake process for aluminum by incubated slices of rabbit kidney cortex. Time-course experiments demonstrated that aluminum uptake was progressive and substantial, with a slice to-medium ratio (S/M) exceeding 20 after four hours of incubation of slices in the presence of 0.01 mM aluminum (as the lactate). Concentration-dependent uptake studies suggested that the process was of limited capacity with maximal tissue uptake of approximately 24 micrograms/gm wet wt. Incubation of slices with aluminum in the presence of metabolic inhibitors (NaCN, 2,4-DNP) demonstrated that about 20-35% of the uptake could be attributed to an energy-dependent component. The calcium channel blockers verapamil, diltiazem and lanthanum decreased S/M aluminum by 65-73% compared to control, suggesting that a calcium dependent process plays a role in aluminum accumulation in renal cortex. Aluminum was not acutely toxic to the renal tubular cells even at a medium concentration of 1.0 mM. PMID- 3353585 TI - Indomethacin in canine acute hemorrhagic pancreatitis. AB - The effects of indomethacin administration on hemodynamics were investigated in canine acute hemorrhagic pancreatitis (AHP). Thirteen mongrel dogs were randomly divided into a fluid treatment group, an indomethacin prophylaxis group (IMP), and an indomethacin therapy (IM) group. Indomethacin (5 mg/kg) was administered as a bolus dosage 30 min before the induction of AHP in the IMP group. In the IM group, indomethacin was also given as a bolus (5 mg/kg) in 5 min starting 30 min after the induction of AHP. AHP was induced with a mixture of trypsin and sodium taurocholate infused into the pancreatic duct. Hemodynamics were monitored during the 4.5 h of surveillance time. Heart rate did not change significantly between the groups. Indomethacin prophylaxis maintained mean arterial pressure at a significantly higher level (P less than 0.05) and prevented the initial fall in blood pressure when compared to the fluid treatment or IM group. Indomethacin increased cardiac output (P less than 0.05) in the IM group, but did not differ significantly in the IMP group in comparison with the fluid treatment group. In conclusion, the inhibition of the initial fall in blood pressure by indomethacin in AHP suggests prostaglandins to play a role in hemodynamic changes and pancreatic shock to be "septic" as evaluated by hemodynamic changes. PMID- 3353584 TI - Meal-stimulated cholecystokinin release and exocrine pancreatic secretion in dogs. AB - To confirm the role of cholecystokinin (CCK) and secretin in digestion, exocrine pancreatic secretion, plasma CCK, and secretin were measured simultaneously in six dogs prepared with gastric and pancreatic fistulas after feeding a solid meal. Plasma CCK concentration determined by radioimmunoassay increased significantly from the basal level, reached a peak 35 min after meal ingestion, and after a dip it further increased toward the end of the 3-h observation. Pancreatic protein output increased significantly, peaked at the fifth 10-min period, and then declined progressively. Plasma CCK concentration and pancreatic protein output correlated significantly during the first postprandial hour. Plasma secretion demonstrated significant elevation at 15 min and a peak at 25 min after a meal. Plasma secretin correlated significantly with both bicarbonate output and flow rate during the 3 h. Simultaneous measurements of plasma CCK and secretin and of pancreatic secretion suggested that postprandial pancreatic secretion is primarily mediated by releases of CCK and secretin, but these hormones do not seem to be the only factors responsible for the secretion. PMID- 3353588 TI - Topics in renal pathology. PMID- 3353586 TI - Calcitonin and granulation tissue formation in the rat. An experimental study. AB - The effects of systemically administered calcitonin (CT) on granulation tissue development were compared using viscose cellulose sponges as wound model in the rat. The ingrowth of new granulation tissue was analyzed for the contents of various connective tissue components (total nitrogen, hydroxyproline, DNA, and RNA) and for the differential counts of the cells infiltrating the sponges. The results indicate that up to 4 weeks postoperatively (p.o.) CT did not affect the net amount of collagen, measured as hydroxyproline, total nitrogen, aminosugars nor the dynamics of differentiation and viability of the invading cells. The present observation that CT has negligible effects, if any, on the early stages of connective tissue formation and on the cell population indicates that surgical procedures could be carried out safely during systemic CT therapy without an increased risk of wound complications. PMID- 3353587 TI - Effect of the larynx on ventilation and respiratory pattern in anesthetized rabbits. AB - The effects of the larynx on ventilation and pattern of breathing have been investigated in anesthetized, spontaneously breathing rabbits. Breathing was either via a tracheostomy or via a supralaryngeal tube in control condition, after laryngeal denervation and after subsequent bilateral midcervical vagotomy. Laryngeal resistance was measured in all experimental conditions when breathing was through the larynx. In control conditions the presence of the larynx in the breathing circuit, as compared to breathing through the tracheostomy, slightly but significantly lowered inspiratory and expiratory airflows, tidal volume, and minute ventilation and increased tracheal pressure. Inspiratory and expiratory durations were not significantly changed. Expiratory laryngeal resistance was higher than inspiratory. Laryngeal deafferentation did not significantly modify values of the respiratory variables. Subsequent motor denervation of the larynx enhanced the decrease in ventilatory parameters due to adding the larynx to the circuit and lengthened the respiratory cycle. Inspiratory laryngeal resistance increased sevenfold and expiratory resistance threefold. Subsequent midcervical vagotomy induced a further increase in inspiratory and expiratory durations and augmented tidal volume independent of the route of breathing, and also reduced laryngeal resistance previously increased by motor denervation. These results reveal the ventilatory effects of the larynx and show the importance of its patency in the pattern of breathing. PMID- 3353589 TI - Nodular renal blastema and metanephric hamartomas in children with urinary tract malformations: a morphologic spectrum of abnormal metanephric differentiation. AB - In a retrospective review, we identified a variety of abnormal immature and differentiated metanephric tissues including nodular renal blastema and metanephric hamartomas in 12 children with urinary tract malformations with or without renal dysplasia. Four infants also had trisomy. Nodular renal blastema was characterized by small subcapsular clusters of primitive metanephric cells, in some cases with evidence of tubular, papillary, or trabecular differentiation. Metanephric hamartomas included papillary adenomas and tubular hamartomas. Undifferentiated renal blastema was multifocal, but more differentiated blastema usually occurred as isolated nodules. When accompanied by renal dysplasia, blastema tended to show differentiation. One child had a spectrum of lesions with both blastema and more differentiated metanephric hamartomas. PMID- 3353590 TI - Quality of care equals patient outcome. PMID- 3353592 TI - Cross-national comparisons of primary health care systems. PMID- 3353591 TI - A comparison of primary care systems in the USA, Denmark, Finland and Sweden: lessons for Scandinavia? AB - In the United States large corporately owned health care delivery institutions, some of which are known as health maintenance organizations (HMOs), are assuming an increased prominence in the provision of primary care (PC). These private organizations are similar in many ways to the public-sector providers that have functioned for decades within the Scandinavian systems. This article explores the similarities and differences between these two PC approaches. This is accomplished by contrasting the governance, organization, financing and staffing of the PC systems of three Nordic countries (Denmark, Finland, and Sweden) to that of the US. Also provided is a critical analysis of the extent to which each model attains the ideal attributes of PC including; 1) accessibility, 2) comprehensiveness, 3) coordination and continuity, and 4) sensitivity to the patient's social milieu. For each facet of PC assessed, the American models offer approaches that are worthy of consideration by Scandinavian clinicians and planners. These include innovations in the areas of coordination between primary and secondary care, preventive care for adults and incentives for financial efficiency. Also, although successful in attaining many attributes of PC, this article discusses some perceived weaknesses of the Scandinavian systems. PMID- 3353593 TI - Referral from general practice to dermatologists. AB - There are many unexplained differences in the rates at which general practitioners make referrals to other medical specialists. We investigated 5,082 referrals from 141 general practitioners to dermatologists in Ringkobing county in Denmark. As an expression of the referral rate to dermatologists an index of referral to dermatologists was estimated for every general practitioner. The index of referral to dermatologists was the number of referrals to the dermatologists per 1,000 patients per year, including children, standardized for age and sex to the average population in Ringkobing County. The following six variables were evaluated in relation to the referral index: 1) Distance to the dermatologists, 2) number of doctors per practice, 3) number of consultations per general practitioner per year, 4) number of patients registered, 5) number of consultations per 1,000 patients per year standardized for age and sex, and 6) number of supplementary procedures per consultation. Stepwise multiple linear regression analysis was used. The study showed that the referral index to dermatologists fell both with distance to the dermatologist and with the number of supplementary procedures per consultation. No correlation was found between the referral index and the four other variables studied. PMID- 3353594 TI - Strain on caregivers of demented elderly people living at home. AB - Forty-six patients with senile dementia and their primary caregivers were studied. The strain score of the caregiver and the mental and behavioural deviation of the patients were estimated. Memory problems, listlessness, apathetic, critical and demanding behaviour and urinary incontinence were the most disturbing features of the patients. Eighty-five percent of the caregivers felt despair and anger and 75% complained of chronic fatigue. There was a statistical significant correlation between caregivers strain on one hand, and duration of symptoms, degree of dementia and deviation of behaviour on the other hand. Elderly women caring for their husbands and daughters caring for their parents were especially at risk. Future services must concentrate on maintaining the ability of caregivers to proceed the caring task. PMID- 3353595 TI - Follow-up in general practice of patients treated for precancer of the cervix uteri. AB - It is known that some patients with invasive cancer of the cervix uteri have previously had a positive vaginal cytology, which was not followed up. More recent investigations have also shown that invasive cancer has developed in patients who were treated for premalignant stages of cervical cancer, but who were not followed up adequately. In Denmark, these patients are advised to attend their practitioner for an annual check. The aim of the present study was to find out if 39 women, treated in a hospital for early cervical cancer, did in fact attend their practitioner for adequate follow-up. Fifteen per cent attended less frequently, and 21% more frequently than recommended, while 64% attended as per the schedule. Women who had undergone surgery for the early stages were significantly better attenders. Women over 30 years of age had a similar tendency, but the difference was not significant. It is suggested that, in the interest of more effective follow-up, registration should be computer-controlled. PMID- 3353597 TI - Consultation among peers in general practice; from no consultation to peer review. AB - The present study concerned several aspects of peer consultation by general practitioners, investigated in a group of 184 doctors (response rate: 83%) who had their vocational training in the department of general practice of the University of Utrecht and practised for at least three years at the time of the study. Questionnaire responses indicated that consultation during and outside surgery hours and participation in case-discussion groups generally extended over more than two years, occurred frequently, and usually pertained to diverse problems associated with diagnosis and treatment. Participation in study and peer review groups extended usually over a shorter time (1 to 1 1/2 years) and the problems dealt with were predominantly the same as for individual consultation. One-third of the general practitioners consulted colleagues frequently and continued to do so for long periods, dealing systematically with a variety of problems; one-third did so infrequently or unsystematically, and one-third did little or not at all. A relationship was found between the setting of the practice and consulting behaviour: 20% of those who practised alone never consulted peers, whereas those in group practices and health centres were accustomed to do so regularly. PMID- 3353596 TI - Users of prescription drugs in Finnish primary care. AB - This study investigates the users of prescription drugs in primary care in Finland in 1976. The data are derived from a national health interview survey, the sample of which represented the whole non-institutionalized population of Finland (N = 21,018). Thirty-two per cent of people 15 years of age or over and 13% of children were using prescription drugs at the time of interview. Women used drugs more than men in all drug categories except for respiratory agents. Children used drugs mainly for respiratory or skin diseases, or for allergic disorders. Cardiovascular agents and analgesics were the most frequently used drugs among the adults. The elderly used all drugs more than other adults except for analgesics, which were used most by the late middle-aged. Characteristics of users of cardiovascular drugs were studied in exploratory multivariate analyses. By far the best predictor of their use was cardiovascular morbidity. In stepwise analyses other significant predictors were age, the visiting to a primary care physician, sex, and work status. Marital status, family income and region appeared not to be statistically significant predictors to the use of cardiovascular drugs. PMID- 3353598 TI - Patterns of psychotropic drug use in a Swedish community. AB - In this study individual data on prescription drug purchases in the total population of a Swedish municipality have been analyzed in order to study changes in the use of psychotropic drugs (in this study mainly hypnotics, sedatives and minor tranquillizers) over time. The number of psychotropic prescriptions decreased by 27% during the twelve-year period 1972-1983. The proportion of psychotropic drug users in the total population decreased from 16 to 11%. This decrease in psychotropic drug use was not evenly distributed within the population. The proportion of users decreased from 10 to 4% in the age group 15 44 years and from 23 to 15% in the age group 45-64 years, while the higher proportion of users in the oldest age group, 65 years and older, only decreased from 33 to 28%. Psychotropic drug use was almost twice as common among females as compared to males throughout the study period. Psychotropic drug use among heavy users of prescription drugs in general--identified with the use of a sex- and age specific definition--was also studied. The decrease in psychotropic drug use during the time period studied was much greater among non-heavy users as compared to heavy users. PMID- 3353599 TI - Proceedings of "Methods for Longitudinal Data Analysis in Epidemiological and Clinical Studies". Workshop sponsored by the National Heart, Lung, and Blood Institute. Bethesda, Maryland, 25-26 September, 1986. PMID- 3353600 TI - The use of lung function tests in identifying factors that affect lung growth and aging. AB - Lung function tests are used both clinically, in assessing disease, and epidemiologically, in identifying those factors which influence the growth and aging process of the lungs. The user must beware of several common pitfalls in the use of these tests, however. First, the commonly used tests of lung function can only identify patterns of dysfunction, not specific pathologic processes. Second, these tests are subject to many sources of intra- and inter-subject variability, making it difficult to dissect out the signal (for example, the rate of lung aging in adults) from the noise which may greatly exceed the signal. Finally, the analysis of longitudinal pulmonary function data is complicated by the alinearity of the growth and aging process, missing data, variable follow-up times, information censoring mechanisms and covariate processes, and problems in defining abnormality. PMID- 3353601 TI - Analysing repeated measurements with possibly missing observations by modelling marginal distributions. AB - Suppose that subjects are observed repeatedly over a common set of time points with possibly time-dependent covariates and possibly missing observations. At each time point we model the marginal distribution of the response variable and the effect of the covariates on that distribution using a class of quasi likelihood models studied in McCullagh and Nelder. No parametric model of dependence of the repeated observations of the subject is assumed. For large samples, the quasi-likelihood estimates of the time-specific regression coefficients over the set of predetermined time points are shown to be approximately jointly normal. This, coupled with various inference procedures, provides a global picture about the effects of the covariates on the response variable over the entire study period. A lack-of-fit test for testing the adequacy of the assumed quasi-likelihood model is also provided. All the methods considered here are illustrated with real-life examples. PMID- 3353602 TI - Likelihood analysis of multi-state models for disease incidence and mortality. AB - Data related to life histories of individuals can be obtained in many different ways, and the usefulness of multi-state models for statistical analysis is generally highly dependent on the type and nature of the data. In this paper, we focus on this, and present an approach to estimation for certain 'difficult' situations associated with retrospective or incomplete prospective observation. The paper begins with the identification of some problem areas in the analysis of data on life history processes. We discuss maximum likelihood estimation in some simple contexts and introduce a pseudo-likelihood which enables the simple analysis of some sampling procedures. This approach is illustrated on standard retrospective and case-cohort designs. PMID- 3353603 TI - Report of a Workshop on Statistical Issues in Longitudinal Studies of Health held in Berlin (West), 23-26 June 1986. PMID- 3353604 TI - Comparison of baseline and repeated measure covariate techniques in the Framingham Heart Study. AB - The purpose of this paper is to indicate how repeated measures on risk factors have been employed in the prediction of the development of disease in the Framingham Heart Study. Since these measures vary over time, the method accounts for time dependent covariates. The technique is a generalized person-years approach in that it treats each observation interval (of equal length) as a mini follow-up study in which the current risk factor measurements are employed to predict an event in the interval. Observations over multiple intervals are pooled into a single sample to predict the short term risk of an event. This approach is compared to the long-term prediction of disease which utilizes only the baseline measurements and ignores subsequent repeated measures on the risk factors. PMID- 3353605 TI - Effect of cigarette smoking in epidemiological studies of lung cancer. AB - This paper describes a method for adjusting the analysis of occupational/environmental lung cancer risks for the effects of cigarette smoking in cohort and case-control studies. The method uses a function that relates an individual's death rate to his age and cigarette smoking history. Two such functions are examined. The first depends on total packs of cigarettes smoked and age. The second, based on the multistage theory of carcinogenesis, depends on age, age at start of smoking, and subsequent smoking rates. The lung cancer rates predicted by these two functions are compared to those observed in cohort studies of male British physicians and U.S. veterans, and in a case-control study of non Hispanic white men in New Mexico. Neither of the cohort data sets distinguished the fit of the two functions. The New Mexico data were fit better by the second function, though both functions overpredicted death rates among ex-smokers. Each function explained substantially more variation in the New Mexico data than did any of several logistic regression models involving categorical variables for age and smoking. PMID- 3353606 TI - Models of the interaction of mortality and the evolution of risk factor distribution: a general stochastic process formulation. AB - Generally analyses of longitudinal studies of chronic disease risks do not directly model the change with time of risk factor values and the interactions of those changes with risk levels. Failure to account for such process characteristics can lead to incorrect inferences about the specific effects of risk factors on mortality, the inability to accurately forecast the future risk of the cohort, and inaccurate statements about the effects of specific risk factor interventions on mortality. We present a model which does describe such a process and show how it can be estimated from longitudinal studies. We also illustrate the effects of certain risk factor process features on the evolution of disease risk data from males in the Framingham, Massachusetts study. PMID- 3353607 TI - Effects of mismodelling and mismeasuring explanatory variables on tests of their association with a response variable. AB - We consider three commonly-used statistical tests for assessing the association between an explanatory variable and a measured, binary, or survival-time, response variable, and investigate the loss in efficiency from mismodelling or mismeasuring the explanatory variable. With respect to mismodelling, we examine the consequences of using an incorrect dose metameter in a test for trend, of mismodelling a continuous explanatory variable, and of discretizing a continuous explanatory variable. We also examine the consequences of classification errors for a discrete explanatory variable and of measurement errors for a continuous explanatory variable. For all three statistical tests, the asymptotic relative efficiency (ARE) corresponding to each type of mis-specification equals the square of the correlation between the correct and fitted form of the explanatory variable. This result is evaluated numerically for the different types of mis specification to provide insight into the selection of tests, the interpretation of results, and the design of studies where the 'correct' explanatory variable cannot be measured exactly. PMID- 3353608 TI - Aspects of the use of relative risk models in the design and analysis of cohort studies and prevention trials. AB - Relative risk regression methods provide a unifying and powerful approach to a range of problems in the design and analysis of cohort studies and prevention trials. Standard partial likelihood-based estimation procedures do not, however, encompass several features that are important in such contexts. Specifically, one may wish to relate disease rates marginally to 'recent' risk factor measurements, whereas a partial likelihood approach requires one to condition on an accumulating risk factor history. Secondly, risk factor values may be ascertained with considerable measurement error, thereby requiring specialized procedures to estimate relative risk parameters. Thirdly, analysis of raw materials to obtain desired covariate (risk factor) histories may involve considerable expense if carried out for the entire cohort. Case-control and case-cohort sampling procedures can avoid much of this expense, but once again partial likelihood estimation procedures require generalization. Such generalizations are described herein. PMID- 3353609 TI - Missing data in longitudinal studies. AB - When observations are made repeatedly over time on the same experimental units, unbalanced patterns of observations are a common occurrence. This complication makes standard analyses more difficult or inappropriate to implement, means loss of efficiency, and may introduce bias into the results as well. Some possible approaches to dealing with missing data include complete case analyses, univariate analyses with adjustments for variance estimates, two-step analyses, and likelihood based approaches. Likelihood approaches can be further categorized as to whether or not an explicit model is introduced for the non-response mechanism. This paper will review the use of likelihood based analyses for longitudinal data with missing responses, both from the point of view of ease of implementation and appropriateness in view of the non-response mechanism. Models for both measured and dichotomous outcome data will be discussed. The appropriateness of some non-likelihood based analyses is briefly considered. PMID- 3353610 TI - Analysis of incomplete multivariate data using linear models with structured covariance matrices. AB - Incomplete and unbalanced multivariate data often arise in longitudinal studies due to missing or unequally-timed repeated measurements and/or the presence of time-varying covariates. A general approach to analysing such data is through maximum likelihood analysis using a linear model for the expected responses, and structural models for the within-subject covariances. Two important advantages of this approach are: (1) the generality of the model allows the analyst to consider a wider range of models than were previously possible using classical methods developed for balanced and complete data, and (2) maximum likelihood estimates obtained from incomplete data are often preferable to other estimates such as those obtained from complete cases from the standpoint of bias and efficiency. A variety of applications of the model are discussed, including univariate and multivariate analysis of incomplete repeated measures data, analysis of growth curves with missing data using random effects and time-series models, and applications to unbalanced longitudinal data. PMID- 3353611 TI - Estimating hidden morbidity via its effect on mortality and disability. AB - The applicability of the theory of partially observed finite-state Markov processes to the study of disease, morbidity, and disability is explored. A method is developed for the continuous updating of parameter estimates over time in longitudinal studies analogous to Kalman filtering in continuous valued continuous time stochastic processes. It builds on a model of filtering of incompletely observed finite-state Markov processes subject to mortality due to Yashin et al. The method of estimation is based on maximum likelihood theory and the incompleteness in the observation of the process is dealt with by applying missing information principles in maximum likelihood estimation. PMID- 3353612 TI - A longitudinal view of blood pressure during childhood: the Muscatine Study. AB - Four thousand three hundred and thirteen children beginning at five to fourteen years of age have been examined on three to six occasions in Muscatine, Iowa, on alternate years. To compare blood pressures throughout the period of observation each value was expressed as a percentile rank. For each subject the average percentile rank (level), the trend in rank and the variability over time were calculated. Values for height, weight, relative weight and triceps skinfold thickness measurements were expressed in the same fashion. There is a relationship between average rank of blood pressure and average rank of body size as well as between trend of blood pressure and trend of body size percentiles. These observations indicate the importance of relative rate of growth in the establishment of the rank order of blood pressure during childhood. PMID- 3353614 TI - Autoregressive growth curves and Kalman filtering. AB - The first part of this paper describes how a Kalman filter can be used to construct maximum likelihood (ML) estimates of autoregressive (AR) and polynomial parameters in polynomial growth curves with AR-1 errors and irregularly-spaced data. The second part introduces a disturbed highest derivative polynomial (DHDP) as a model for growth curves. This model does not depend on regression coefficients. Variances of the highest derivative disturbance and the observation error are estimated (by ML) using a Kalman filter. The estimated DHDP growth curve is obtained by optimally smoothing the output of the filter. Equally spaced data is not required. The DHDP model and analysis are developed for an individual and extended to a population growth curve using data from many individuals with covariates. PMID- 3353613 TI - Autoregressive modelling for the analysis of longitudinal data with unequally spaced examinations. AB - Missing and/or unequally spaced examinations are often present in longitudinal studies. An autoregressive model is presented for the analysis of such data for continuous outcome variables. The fitting of the model can be accomplished by weighted non-linear regression methods available in standard statistical packages. Some features of the model include consideration of both time-dependent and fixed covariates, assessment of the relationships between changes in outcome and exposure over short periods of time, and use of all available person-time for an individual. An illustration looking at the role of personal cigarette smoking on changes in pulmonary function in children is included. PMID- 3353615 TI - Issues in the analysis of repeated categorical outcomes. AB - This paper discusses statistical methods for the analysis of repeated observations of categorical variables as they might arise in longitudinal studies. Two general types of models are described: marginal models that give representations for the marginal distribution of response at each occasion, and transitional models that give representations for the transition probabilities between outcome states at successive occasions. The conceptual and technical differences are discussed and recent work advancing both approaches is reviewed. The two approaches are illustrated through analysis of repeated observations on interval history of the respiratory symptom 'persistent wheeze' in preadolescent children. PMID- 3353616 TI - Development of techniques for the detection of blood doping in sport. AB - Increased performance after blood transfusion was first demonstrated 40 years ago, but the technique did not create attention until the early 1970s when it was dubbed 'blood doping' by the media. The procedure can increase both maximal oxygen uptake (VO2max) and performance in endurance sports. It was forbidden by the International Olympic Committee (IOC) after the 1984 Olympics, despite the fact that no methods had been devised for unequivocal detection. There are 2 types of blood transfusions: either from a matching donor (heterologous transfusion) or reinfusion of the subject's own blood (autologous transfusion). While the subject's haemoglobin normalise, blood can be stored in commercially available blood bags for 4 to 5 weeks in a 'blood bank' (+4 degrees C), or as frozen erythrocytes with a storage time up to several years. A blood doping procedure, independent of transfusion type, induces some pronounced physiological changes. A desired effect of blood doping is the increased total red blood cell mass leading to increments in haemoglobin, which after successfully induced blood doping is in the magnitude of at least 10%. In addition, storing of blood leads to a constant decline in RBC count due to the limited life span of the RBC (haemolysis). Thereby, serum iron and bilirubin levels will increase and reach maximal levels within the first day. Haemolysis is more accentuated after storing of blood in a blood bank than in the frozen state. The regulation of RBC formation is mediated through a negative feed-back mechanism via the glucoprotein hormone erythropoietin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353618 TI - Soft tissue sarcomas. PMID- 3353620 TI - Patterns of metastatic spread following resection of extremity soft-tissue sarcomas and strategies for treatment. AB - This study examines recurrence patterns in 255 patients with soft-tissue sarcoma treated with preoperative chemotherapy and radiation, followed by limb-sparing surgery. Eighty-five patients developed metastatic disease: 13 had isolated local recurrence, 43 had isolated pulmonary metastases, 11 had metastases to lung and elsewhere, and 18 had metastases to multiple sites. Of the patients with isolated pulmonary metastases, 19/43 had resection of the metastases, and 9 are disease free. All 13 patients with local recurrences had resection of the recurrence, and 9 remain disease-free. Patients with multiple sites of recurrence had a 2-year survival of less than 10%. Resection of metastases is beneficial to a small number of patients who develop metastatic disease. PMID- 3353617 TI - Heredity and trainability of aerobic and anaerobic performances. An update. PMID- 3353619 TI - Soft-tissue sarcoma: initial characteristics and prognostic factors in patients with and without metastatic disease. AB - Five hundred and sixty-five patients with soft-tissue sarcoma were admitted to Memorial Sloan-Kettering Cancer Center from July 1, 1982 to July 1, 1985. Clinical and pathologic factors were analyzed to identify initial characteristics and to determine factors associated with prognosis and the development of metastasis. In decreasing order of frequency, the most common sites of primary tumor were the extremity (51.1%), retroperitoneum/viscera (28.8%), trunk (15.9%), head and neck (3.7%) and breast (0.4%). The most common histologic types were liposarcoma (21.4%), malignant fibrous histiocytoma (20.2%), leiomyosarcoma (20.0%), fibrosarcoma (11.0%), and tendosynovial sarcoma (9.6%). One hundred and twenty-eight patients (22.7%) had metastases in a median follow-up period of 19 months. Metastasis was more common in patients with retroperitoneal and visceral sarcomas than in patients with extremity sarcomas. Patients with leiomyosarcomas were more likely to develop metastases than those with other histologic types. Fibrosarcoma and liposarcomas were the least likely to develop metastases in this time frame. Tumors greater than 5 cm in diameter occurred more frequently in patients with metastases. Actuarial survival was related to the site of primary tumor and the histologic type and grade of malignancy. Multivariate analysis indicated that patients with low-grade sarcomas, extremity sarcomas, and fibrosarcomas and patients without metastatic disease demonstrated significantly improved survival. In patients with metastases, disease-free interval (less than 365 or greater than or equal to 365 days) was significantly related to overall survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353621 TI - Histological diagnosis and grading of soft-tissue sarcomas. AB - Grading methodology for soft-tissue tumors is not yet unequivocally established. The authors use a system that is an elaboration upon that of the National Cancer Institute: grade 1 or low-grade lesions are malignant lesions with minimal risk of metastases with a tendency for local recurrence if not totally excised, and with a capability for progression to a higher grade with recurrence; grades 2 and 3 are high-grade lesions with a significant risk of metastases; grade 2 are lesions with intermediate aggressiveness, and grade 3 are highly malignant lesions with dissemination early in the course of the disease. Whereas the great majority of grade 3 lesions recur within 24 months of the initial diagnosis, patients with grade 2 lesions may go recurrence-free beyond 36 months. Although more experience is needed in grading soft-tissue sarcomas, it is hoped that grading will continue to contribute to the management of patients with malignant tumors of the soft tissue. It represents an adjunct to histological typing, which is useful in conveying the degree of biological aggressiveness as judged by histological features. Histologically 80% of the lesions can be classified on the basis of hematoxylin and eosin-stained sections and other conventional special stains. In some instances electron microscopy and immunohistochemistry are necessary for histotyping. The most challenging area for histopathological differential diagnosis remains the distinction of tumor-like reactive conditions, and pleomorphic benign tumors from sarcomas. PMID- 3353622 TI - Prognostic factors for local recurrence and survival in patients with localized extremity soft-tissue sarcoma. AB - The charts of 423 patients with localized extremity soft-tissue sarcoma treated at our institution over a 10-year period (1968-1978) were reviewed. Data were subjected to both univariate and multivariate analysis, with independent variables in the multivariate analysis appearing in capital letters. Factors associated with an increased risk of local recurrence included the following: AGE greater than 53; PRESENTATION WITH RECURRENT DISEASE; HIGH TUMOR GRADE; positive regional nodes; TREATMENT BY LIMB-SPARING SURGERY (LSS); invasion of vital structures (LSS only); INADEQUATE MARGINS; and biopsy with delayed definitive resection. Survival was adversely affected by the following: AGE greater than 53; PAINFUL MASS; PROXIMAL SITE; SIZE greater than or equal to 10 cm; HIGH TUMOR GRADE; POSITIVE NODES; invasion of vital structures; TREATMENT BY AMPUTATION; INADEQUATE MARGINS; and local recurrence after treatment at our institution. Significant variations in both local recurrence and survival according to histopathology were also observed, with EMBRYONAL RHABDOMYOSARCOMA, ANGIOSARCOMA, and MALIGNANT PERIPHERAL NERVE TUMORS emerging as independent predictors of local recurrence. Using the Cox models for local recurrence and survival, patients were stratified into high-, intermediate-, and low-risk categories based on the presence or absence of each variable. Risk factor analysis should be part of the overall evaluation of each patient with extremity sarcoma. PMID- 3353623 TI - Selective combination of modalities in soft tissue sarcomas: limb salvage and survival. AB - One hundred fifty-two consecutive patients with soft tissue sarcomas were operated in the period 1977 through 1985. Eighty-seven patients with minimum resection margin of 2 cm or greater had no further local therapy, whereas 65 patients with minimum margin less than 2 cm had adjuvant postoperative radiation. Of 121 patients with extremity sarcomas, only 5 (4%) were managed with amputation. The overall 5-year survival rate is 58%, and for patients with extremity tumors, 67%. The 5-year local recurrence rate in extremity sarcomas was 10% for patients with minimum surgical margins 2 cm or greater and no further local therapy, and 6% for those with lesser surgical margins and adjuvant postoperative radiation. With selective combination of modalities limb salvage can now be practiced in 96% of the patients with acceptable local control and survival rates. PMID- 3353624 TI - Surgical management of soft tissue sarcomas, with an analysis of 313 cases. AB - From 1964 to 1978, 313 patients, 192 males and 121 females, with soft tissue sarcoma underwent surgery in our hospital. All patients have been followed up for over 5 years. One hundred ninety patients (60.7%) had recurrence of the tumor after previous surgery. The tumor was located in the head in 55 cases, in the trunk in 136, and in the extremities in 122 cases. Regional lymph node metastases occurred in 23 patients (7.4%). Fibrosarcoma, neurofibrosarcoma, and rhabdomyosarcoma were the types most commonly encountered in this series. The 5 year survival rate, according to the extent of surgical resection for 117 patients with local resection, was 47.9%; for 75 patients with wide local resection, 62.7%; for 43 patients with amputation, 18.6%; and for 78 patients with local resection combined with irradiation, 48.7%. For the whole series, the 5- and 10-year survival rates were 47.6% and 35.8%, respectively. The 5-year survival rates of stages I, II, III, and IV (TNM classification) were 60%, 46.9%, 40%, and 22.2%, respectively. PMID- 3353625 TI - Meningitis caused by Streptococcus suis in humans. AB - Between 1968 and 1984, 30 strains of Streptococcus suis causing meningitis were isolated in the Netherlands. Twenty-eight strains were type 2, one was type 4, and one was untypable. The average age of the patients infected with these strains was 49 years (range, 21-76 years); the male-to-female ratio was 6.5. Twenty-five patients (83%) were employed in the pork industry. Two patients (7%) died. In seven cases (23%), predisposing factors were identified. The most frequent sequela was hearing loss (54% of surviving patients). The data for these 30 patients were compared with those for 30 patients from outside the Netherlands whose cases of meningitis due to S. suis type 2 were described between 1968 and 1985. No differences were found. The estimated annual risk of developing S. suis meningitis among Dutch abattoir workers and pig breeders was approximately 3.0/100,000--a rate 1,500 times higher than that among persons not working in the pork industry. PMID- 3353626 TI - Assessing and modeling heterosexual spread of the human immunodeficiency virus in the United States. AB - Epidemiologic investigation of the AIDS epidemic among heterosexuals has consisted chiefly of studies of partners of individuals infected with the human immunodeficiency virus (HIV) and population surveillance. Heterosexual partners of infected individuals appear to be at high risk of infection, but only a small proportion of cases of AIDS have been attributed to heterosexual contact in the United States and Europe. An epidemic model for heterosexual spread of HIV infection is developed and fit to surveillance data. Fitted values are restricted to a range consistent with findings from partner studies. Because, at present, most HIV-infected heterosexuals and bisexuals have been infected through other means (intravenous drug use or homosexual contact), the model considers two interacting populations: a small population of individuals rapidly infected by high-risk activity and a large population of individuals at risk only from heterosexual contact. No precise predictions concerning the AIDS epidemic among heterosexuals are possible now, but current epidemiologic findings neither predict nor preclude a major heterosexual epidemic. Projections depend strongly on the delay between infection and infectivity. The model can also be used to demonstrate how interpretation of results of case-control studies of HIV infection depends on underlying assumptions about the dynamics of the epidemic. PMID- 3353627 TI - AIDS and biomedical research funding: comparative analysis. AB - One of the critical policy questions raised by the AIDS epidemic is the proper size of the United States federal government's commitment to AIDS-related research. The extent of the federal government's investment in AIDS-related research in relation to research investments in cancer, coronary heart disease, and unintentional injuries is examined. Appropriation levels for fiscal year 1986 are divided by indexes of projected disease burden for 1991 to create a research investment ratio for each health impairment. Indexes of disease burden include numbers of total deaths, early deaths, expected life years lost, and discounted life years lost and direct economic costs. Despite the uncertainty about the future of the AIDS epidemic, there is no indication that AIDS is being overfunded relative to cancer and heart disease. Injuries appear to receive relatively low funding priority. Confident conclusions about research priority depend upon resolution of qualitative considerations and better understanding of the dynamics of the AIDS epidemic. PMID- 3353628 TI - Infectious disease rounds: deteriorating neurologic status in a young woman with schizophrenia. PMID- 3353629 TI - Q fever in Spain: acute and chronic cases, 1981-1985. AB - Two hundred forty-nine cases of Q fever were documented at the laboratories of the Centro Nacional de Microbiologia, Virologia e Inmunologia Sanitarias (CNMVIS) during the 5-year period 1981-1985. Two hundred thirty-four cases corresponded to acute infections, mostly sporadic but including two epidemics. The clinical presentation was respiratory in 74% of the cases and febrile in 18%. Fifteen cases, all but one of which were endocarditis, were categorized as chronic. The cases studied were referred from almost every region of Spain. The clinical and epidemiologic analyses and the number of cases reported permit only an approximation of the true incidence and characteristics of Q fever in Spain. PMID- 3353630 TI - Nosocomial bacteremia in a large Spanish teaching hospital: analysis of factors influencing prognosis. AB - Five hundred forty-three episodes of nosocomial bacteremia were prospectively followed in a large Spanish university hospital. The commonest isolates were Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida species. The most frequent sources of infection were intravenous lines, urinary tract, and lower respiratory tract. Overall mortality was 18%. A step-forward logistic regression analysis defined eight variables independently influencing the outcome: shock, underlying rapidly fatal disease, high-risk source of bacteremia (intraabdominal, lower respiratory tract, or not identified), age more than 70 years, hospitalization in intensive care or medical units, inappropriate antibiotic treatment, infection due to a high-risk microorganism (P. aeruginosa, Serratia marcescens, Klebsiella, Bacteroides, or Candida), and development of septic metastasis. The identification of those factors independently influencing the outcome and their possible modification may represent a further step in the control of nosocomial bacteremia by improving its prognosis. PMID- 3353631 TI - The nature of human brucellosis in Kuwait: study of 379 cases. AB - Three hundred seventy-nine Kuwaiti patients with brucellosis were admitted to Adan General Hospital, Kuwait, during the period 1984-1985. Of these 231 were males and 148 were females. Diagnosis was based on symptoms and signs compatible with the disease and on the detection of significantly elevated antibody titer and/or positive blood culture. The primary means of exposure were the consumption of raw milk and contact with goats, sheep, or camels. Patients most frequently presented with fever (91%), chills (40%), sweats (39%), gastrointestinal symptoms (30%), headache (23%), respiratory symptoms (23%), and musculoskeletal symptoms (22%). The major signs were osteoarticular involvement (37%), hepatosplenomegaly (27%), and lymphadenopathy (9%). Different regimens of treatment were used, but the highest rate of cure was achieved with triple therapy--tetracycline, streptomycin, and rifampin. PMID- 3353633 TI - [The woman and fertilization. The experience of in vitro fertilization in a case study]. PMID- 3353632 TI - Anorectal infections in patients with malignant diseases. AB - Fifty-seven episodes of anorectal infection in 44 patients with malignant diseases primarily leukemia or lymphoma, have been retrospectively reviewed. Seventeen patients died in hospital, but only in seven cases was the anorectal infection a major contributing cause of death. The most important prognostic indicator of outcome was number of days of neutropenia during the infectious episode. Cultures obtained at the time of surgical drainage or by needle aspiration of the wound revealed multiple organisms in 26 of 29 instances, and anaerobic organisms were the commonest isolates. Anorectal infection was controlled in 28 (55%) of 51 treatment courses when antibiotics were the only treatment given. However, if the antibiotic regimen included both an aminoglycoside and an antibiotic with anaerobic coverage, control of infection was observed in 15 (88%) of 17 cases. There were 26 surgical procedures performed, with acceptable morbidity. Infection was controlled in 19 (73%) of 26 cases treated with surgery and antibiotics. The results support managing most of these infections initially with medical treatment, using an antibiotic regimen that includes an aminoglycoside and a specific drug against anaerobes. Surgery is recommended if there is obvious fluctuance, a significant amount of necrotic tissue evident, or progression of the infection locally or continued sepsis after an adequate antibiotic trial. PMID- 3353634 TI - [Dental caries. Its incidence and prevalence]. PMID- 3353635 TI - [Training in communication. A necessity for nursing]. PMID- 3353637 TI - [Patient care. Clinical epidemiology]. PMID- 3353636 TI - [Benefit of health exams]. PMID- 3353638 TI - [The perception of becoming ill]. PMID- 3353639 TI - [Nursing care of pressure ulcer patients]. PMID- 3353640 TI - [Cooking for the day care center (I)]. PMID- 3353641 TI - [Home care. The Cantera Primary Care Center]. PMID- 3353642 TI - [Alma Woolley, dean of the School of Nursing of Georgetown University. Nursing, a humanistic bond between people and technology. Interview by Rosalia Rodriguez Garcia]. PMID- 3353643 TI - Practical ways to snuff out stress. PMID- 3353644 TI - My sister isn't the only one who won't forget her nurses. PMID- 3353645 TI - How nursing takes over when medicine gives up. PMID- 3353646 TI - The heart and soul of hospice nursing. PMID- 3353647 TI - Preventing and treating geriatric infections. PMID- 3353648 TI - A worst-case guide for any case of psoriasis. PMID- 3353649 TI - The new wave in lithotripsy: implications for nursing (continuing education credit). PMID- 3353650 TI - Do COPD patients really need to manipulate you? PMID- 3353651 TI - A keep-your-cool guide to giving a deposition. PMID- 3353652 TI - Living with AIDS. PMID- 3353653 TI - Making pain control easy. PMID- 3353654 TI - [Differential diagnosis of hyperdense space-occupying lesions of the cerebral hemisphere in computerized tomography]. AB - A CT survey of the most frequently encountered hyperdense space-occupying lesions in the region of the cerebral hemispheres. Description of differential diagnostic deliberations. PMID- 3353655 TI - [Clinical course, electrophysiologic monitoring and neuroradiologic findings in acute basilar artery thrombosis and local fibrinolytic therapy]. AB - The development of new catheter materials and techniques has made it possible to perform local intraarterial fibrinolysis in the region of the basilar artery in case of thrombotic arterial occlusions. We present the case of a 27-year old patient suffering from thrombosis of the basilar artery in whom local fibrinolysis was performed. The clinical course is demonstrated in respect to imaging methods (angiography, CT and MRT) and electrophysiological monitoring. PMID- 3353656 TI - Localised form of spondylo-epiphyseal dysplasia congenita. AB - We report an unusual case of spondylo-epiphyseal dysplasia congenita which affected only the hips and the thoraco-lumbar spine. The epiphysis of the long bones are normal apart from the hips. Our child has a bilateral epiphyseal dysplasia of both proximal femoral epiphysis discovered incidentally at 11 months and confirmed later on at 8 years, associated with abnormalities of the superior margin of the vertebral bodies from T11 to L2. Very few similar cases have been reported anteriorly. PMID- 3353657 TI - [Spondylolysis/spondylolisthesis--a new thesis of its etiology]. AB - Attention is drawn to the mode of development of spondylolysis/spondylolisthesis and to the fact that the articular processes of the small vertebrae can exercise an action on the pars interarticularis only if the latter are in oblique position. It is pointed out that the requisite obliqueness of the pars interarticularis is only possible in conjunction with lordosis, so that the latter is an essential condition for the pathogenesis of spondylolysis/spondylolisthesis. It is also pointed out that excessive load due to upright position of the subject is the triggering factor for spondylolysis/spondylolisthesis, because it is only from this position that the articular processes of the small vertebrae can exercise an action on the pars interarticularis. In four-footed animals there is no excessive load on the articular processes because they do not walk or sit upright, which means the articular processes cannot act on the pars interarticularis to trigger spondylolysis/spondylolisthesis. Likewise, there are no vibrations of the vertebral column with lordosis as the inevitable result and consequently there is no spondylolysis/spondylolisthesis. Hence, it is only in humans that the preconditions and triggering factors for spondylolysis/spondylolisthesis exist at all. PMID- 3353658 TI - [Has the new roentgen legislation been understood? 10 clinical questions concerning the new roentgen legislation]. PMID- 3353659 TI - [Differential CT diagnosis of tumors of the cranial calotte with intracranial spread based on a case report]. AB - A report on patient presenting in the cranial computer tomogram with changes in the cranium in the left temporal region typical of a meningioma, as well as with changes in the floor of the middle cranial fossa. Correct diagnosis was obtained only by the overall assessment comprising anamnesis, laboratory findings and state of the skeletal structure: namely, a plasmacytoma involving the calotte of the cranium. PMID- 3353661 TI - [The France team at Anaheim]. PMID- 3353660 TI - [The 7th symposium of Berck hospitals. Berck-sur-Mer, 17 October 1987. Prolonged post-traumatic coma]. PMID- 3353662 TI - [Lymphedema of the upper limb]. PMID- 3353663 TI - [Treatment of diabetic arteriopathy of the lower limbs]. PMID- 3353664 TI - [Buerger's disease or thromboangiitis obliterans]. PMID- 3353665 TI - [Ehlers-Danlos syndrome: clinic and genetic aspects and molecular basis]. PMID- 3353666 TI - [Emergencies in peripheral arterial pathology]. PMID- 3353667 TI - [Peroperative hemodynamic monitoring]. PMID- 3353668 TI - [Economics of blood products: the value of normovolemic hemodilution]. PMID- 3353669 TI - [Value of paraclinical tests for the preoperative evaluation of cardiac risk in anesthesiology]. PMID- 3353670 TI - [Preoperative exploration of hemostasis]. PMID- 3353672 TI - [Relations between trabecular bone mass and the configuration in the space of the trabeculae of bone. Histomorphometric study of a population of 145 osteoporotic women]. AB - 145 women with involution osteoporosis and at least one vertebral compression noted on X-Rays, underwent a biopsy of the iliac wing and measurement of the mean cortical thickness, trabecular bony volume and parameters concerning the spatial configuration of bony trabecules (MTPT = Mean Trabecular Plate Thickness, MTPD = Mean Trabercular Plate Density, MTPS = Mean Trabecular Plate Separation), reflecting respectively the thickness, the density and the separation of the trabecules. The results were compared with those of a series of 22 control women of the same age. The post-menopausal osteoporotic patients present a decreased VTO, MTPD and MTPS with normal MTPT. Patients with senile osteoporosis show no difference as compared to the control patients of the same age. Half of the patients had a VTO higher than the spontaneous vertebral fracture threshold. Involution osteoporosis where the VTO exceeds the threshold present a significant decrease of the number of bony trabecules without decreased thickness. There is a negative correlation between age and the number of trabecules; a linear correlation between VTO and thickness, between VTO and trabecular density confirming the close relationship between mass and spatial configuration of the bone. There is a geometric configuration between density and separation of the trabecules, indicating a great sensitivity of the microstructural framework of disorganized trabecular bone. These data show that a decreased bony mass is not the only physiopathological mechanism observed during involution osteoporosis. Alterations of the spatial configuration of the trabecules or the mechanical resistance of the bony matrix are additional factors, the role of which might have been underestimated. PMID- 3353671 TI - [Assay of erythrocyte, platelet and serum superoxide dismutase, glutathione peroxidase and catalase in rheumatoid polyarthritis]. AB - The authors present a study of superoxide dismutase, catalase and glutathione peroxidase in hemolysis product, platelets and serum of 23 patients with rheumatoid polyarthritis and 11 healthy subjects. The nature of the treatment enables to divide the 23 patients into 3 groups: group I (8 cases): no treatment; Group II (7 cases): steroid therapy alone; group III (8 cases): basic treatment associated (3 cases) or not (5 cases) to steroid therapy. Statistical analysis shows no significant difference, whatever the environment and the treatment contemplated. The significance of these results is discussed and compared with literature data concerning only enzymatic activities and not the blood levels as in the present study. PMID- 3353673 TI - [Prognostic and therapeutic significance of bone marrow biopsy in multiple myeloma. Analysis of 31 stage II A and III A patients]. AB - The prognostic value of bone marrow biopsy was established in 31 patients suffering from stage IIA and IIIA myeloma (Durie and Salmon classification). Data obtained from quantitative marrow cytology permit to differentiate 3 sub-groups of cells: plasmocytes, plasmoblasts, plasmocytes/plasmoblasts of which the incidence on the prognosis and the response to treatment was studied. There is a correlation between the response to MP and the nature of various cells populations and, on the other hand, the type of infiltration. A sub-group of patients, resisting to MP, was identified: diffuse plasmoblastic myelomas of poor prognosis. Induction poly-chemotherapy seems far superior over the MP combination, which was always a controverted issue. PMID- 3353674 TI - [Arthroscopy of the hip]. AB - In reference to 50 arthroscopies performed since january 1983, we describe a simplified approach to the hip. This joint may be divided, from the standpoint of arthroscopic anatomy, into a coxo-femoral area per se and a peripheral area. The latter represents the most interesting part from a rheumatologist's standpoint. This is the area that our method enables to study quite easily. With the macroscopic study and the possibility of controlled biopsy or biopsy under direct vision, arthroscopy realizes an additional diagnostic approach to questionable hips. It represents already a new therapeutic approach in hip chondromatosis. PMID- 3353675 TI - [Matched immunological study of serum and synovial fluid in 68 patients with rheumatoid polyarthritis]. PMID- 3353676 TI - [Assay of polyisoadenylates (2-5A) in the blood of patients with ankylosing spondylarthritis or psoriatic rheumatism]. PMID- 3353677 TI - [Acute inflammatory spondylitis caused by spontaneous lysis of calcifying nucleopathy]. PMID- 3353678 TI - [Pseudotumoral form of calcified hematoma]. PMID- 3353679 TI - [Experimental studies on the factors of osteogenesis by transplantation of patellar cartilage framework in rats]. AB - The cartilage framework of the patella in rats is capable of inducing ossification after homotransplantation in many various sites: muscle, thyroid, testicle, ovary, kidney, anterior chamber of the eye, etc. The frequency of ossification does not depend on the technical conditions of the transplant, but on the age of the donors and receivers; it approximates 84 p. cent when the two rats are three weeks old. It is close to 100 p. cent in case of autotransplant. It is non-existent in case of heterotransplantation. A cartilage that is killed by alcohol or cold, has no longer osteogenetic abilities, even if it is placed in contact with live cartilage. The transplant of patellar cartilaginous framework represents a model which may be used to study the factors responsible for physiological ossification as well as the effect of various experimental conditions on osteogenesis. PMID- 3353680 TI - [Value of orthesis canes in rheumatoid polyarthritis]. PMID- 3353681 TI - [Reactional ureaplasma urealyticum arthritis]. PMID- 3353682 TI - [Kagger's triangle in arthritis urica]. PMID- 3353683 TI - [Plasma fibronectin and proteins in biological inflammation. Study of statistic relations]. PMID- 3353684 TI - [Polyarthritis in Gougerot-Sjogren syndrome or sarcoidosis?]. PMID- 3353685 TI - [HLA and familial scleroderma]. PMID- 3353686 TI - Effects of culture substrates and normal hepatic sinusoidal cells on in vitro hepatocyte synthesis of Apo-SAA. AB - Primary hepatocyte cultures synthesize apo-SAA upon stimulation with supernatant from lipopolysaccharide (LPS)-treated macrophages. The matrices on which the hepatocytes were grown influence their basal apo-SAA synthetic capability. Fibronectin was superior. Coculturing hepatocytes with hepatic sinusoidal cells did not adversely affect the ability of hepatocytes to synthesize and secrete apo SAA into the culture medium. In 72 h, clear islands of endothelial cells nestled in layers of hepatocytes. Both apo-SAA and apo-SAA were made in considerable quantities but no evidence could be obtained that the apo-SAA were free of apo-A 1. The coculturing of hepatocytes with liver sinusoidal cells, the site of ultimate AA deposition, is a first step in establishing an in vitro system for AA amyloidogenesis. PMID- 3353687 TI - Features of the in vitro established rat large granular lymphocyte leukaemia RNK 16. AB - A large granular lymphocyte (LGL) leukaemia cell line from the Fisher/F344 rat strain called RNK-16 has been established in vitro, maintaining the same surface markers as tumour cell growing in vivo. The tumour has also maintained its specificity pattern and cytotoxic reactivity and serves as a suitable source of natural killer (NK)-like effector cells in vitro. The cells show no evidence of dependency on, or production of, interleukin 2 or interferons, nor is the cytotoxic capacity influenced by treatment with mitogens. The in vitro line does not produce natural killer cytotoxic factor (NKCF) in a constitutive manner, but can be induced to do so via coculture with tumour target cells. When the fine specificity patterns were analysed, the RNK-16 cells express species-preferential lysis of susceptible target cells and a highly discriminatory power to kill only 1 out of 5 rat erythroleukaemia cell lines. When testing normal target susceptibility patterns, RNK-16 kills lymphoblasts of B type better than T blasts, which is well in line with previous findings on normal NK cell specificity patterns. PMID- 3353688 TI - Autoantibodies from rheumatoid arthritis patients recognize antigens on the synoviocyte surface. AB - We have found autoantibodies in the sera from rheumatoid arthritis (RA) patients which recognize two cell surface antigens of approximately 70 kDa and 28 kDa from synoviocyte extracts as detected by immunoprecipitation analysis. These polypeptides were immunoprecipitated from extracts containing mainly macrophage like synoviocytes (type A) but not from extracts of homogeneous fibroblast-like synoviocytes (type B). These autoantigens are not selectively expressed by RA synoviocytes, since both RA and non-rheumatoid synovia were reactive for RA sera. From the panel of different RA sera tested, 64% immunoprecipitated the 70 kDa band, and 27% recognized the 28 kDa polypeptide. These differences in the specificity of the sera seemed to be related to the clinical state of the donor. The sera from patients suffering from other autoimmune diseases such as autoimmune thyroiditis and systemic lupus erythematosus (SLE) do not appear to be reactive for these specificities, but sera from patients with Sjogren's syndrome, psoriatic arthritis, and Crohn's disease showed a weak cross-reactivity with the 70 kDa polypeptide. This autoreactivity against synovial cells in RA supports the idea that these cells participate in the initial immune response of the disease. PMID- 3353689 TI - Immunization with nanogram quantities of nitrocellulose-bound antigen, electroblotted from sodium dodecyl sulphate-polyacrylamide gels. AB - Intrasplenic immunization with antigen immobilized on nitrocellulose (NC) paper results in an immune response with nanogram amounts of antigen without the use of Freund's adjuvant. Comparing the sensitivity of the intrasplenic immunization with intraperitoneal or subcutaneous administration, we found that the intrasplenic method resulted in more positive animals with higher titres than did the other techniques with the smallest amount of antigen (70 ng of bovine serum albumin). With larger amounts of albumin the intraperitoneal method yielded the highest titres. No loss of antigenicity was observed when we immunized with equal amounts of protein separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotted and stained with either Coomassie brilliant blue R 250 or Amido black 10 B. PMID- 3353690 TI - The organ distribution of F protein in the mouse. AB - F protein is of unknown function and found principally in the liver, with smaller amounts detectable by gel diffusion and immunostaining in kidney and brain. By taking advantage of a newly developed radioimmunoassay, capable of detecting down to 1 ng ml-1 of F protein, the organ distribution of this molecule in the mouse was re-examined. F protein was not confined to the previously known tissues and indeed was detected at different levels in every organ studied. The highest concentration (6-10 mg g-1 wet tissue) was found in the liver, but significant amounts (2-25 micrograms g-1) were also found in kidney, heart, and brain. Lower quantities were detectable in all other tissues studied. The presence of F protein in the thymus, and the lack of tolerance to this in bone marrow chimaeras between mice of different F protein types, places certain constraints on the amount and/or location of a protein required for tolerization. PMID- 3353691 TI - Disturbed iron metabolism among workers exposed to organic sulfides in a pulp plant. AB - The aim of this study was to investigate a possible relationship between exposure to sulfides and disturbances of the synthesis of heme and the erythrocytes. Eighteen workers exposed to sulfides at a pulp and paper plant were examined and compared with individually matched referents from a thermomechanical pulp plant without such exposure. The exposure levels of methylmercaptan, dimethylsulfide, and dimethyldisulfide were low. However, five subjects were exposed to high levels of short duration, and their data were analyzed separately. The activity of the enzymes delta-aminolevulinic acid synthase and heme synthase in reticulocytes, characteristics of the erythrocytes, and the iron status were analyzed. A minor decrease, not statistically significant, was observed for the enzymes among the five highly exposed subjects. However, the concentrations of iron and transferrin were elevated and the concentration of ferritin was low in comparison to the corresponding levels of the referents. This combination will not occur spontaneously. A previous study indicated that sulfides may inhibit heme synthesis, and the present study suggests that they may also disturb iron metabolism. PMID- 3353692 TI - Medical consequences of work-related accidents on 2,454 Swedish farms. AB - The medical consequences of accidents related to work on 2,454 farms in two Swedish rural municipalities were studied. The objectives were to describe the nature and scope of the injuries incurred, to collect data for the health planning procedure, and to test a local system for continuous injury surveillance in emergency care. All the injuries of 163 patients during the period 1 January 31 December 1983 were analyzed with regard to diagnosis, severity, medical treatment, hospitalization, and temporary and permanent disability. Wounds, contusions, fractures, foreign bodies, sprains, and strains constituted the main diagnostic groups. Injuries to the fingers, head and face (including the eyes), feet, and legs dominated. Six percent of the patients were admitted to the hospital. Seventy-five patients were put on temporary disability for a total of 2,431 d. For 62 of these patients the injuries were classified as minor. Permanent disability was observed in 4% of the cases. The study emphasizes the importance of registry criteria when one is comparing different injury surveillance systems. The majority of the injuries could have been prevented by the proper use of appropriate personal safety equipment. The results may serve as a basis for general measures to improve local safety consciousness. PMID- 3353693 TI - Risk for reduced sperm quality among metal workers, with special reference to welders. AB - The purpose of this study was to investigate whether men employed in the metal industry have sperm of poorer quality than men in other types of work. A postal questionnaire was sent to men employed in the metal industry, certain other types of nonmetal industries, and other types of employment in which the factors suspected to influence sperm quality were not present. By means of this questionnaire survey, it was hoped to define the possible influences of the work environment on sperm quality. Out of the total of 3,119 men included in the investigation, 2,517 (81%) filled out the questionnaire satisfactorily. Semen analysis was performed for all 3,119 men. There was a greater risk for poor sperm quality among welders than among men not employed in welding. The risk for poor sperm quality was increased for those welders who worked with stainless steel. Welding in general, and specifically with stainless steel, is connected with a risk of reduced sperm quality. PMID- 3353694 TI - Ultrastructural changes in peripheral nerves of the fingers of three vibration exposed persons with Raynaud's phenomenon. AB - A finger biopsy was performed on three patients with vibration-induced white finger (VWF), and the specimens were examined by electron microscopy for peripheral nerve changes. A characteristic neuropathy with perineurial fibrosis was revealed which was often accompanied by a thickened perineurium with a lamellar structure resembling onion skin. This peculiar fibrosis consisted of elongated cytoplasmic projections of perineurial cells or fibroblasts and a greatly increased amount of collagen which occasionally contained fibrous long spacing collagen. In the endoneurium, a decrease in the number of nerve fibers and a marked increase in collagen with fibroblasts were noted. Myelinated axons became smaller, and this occurrence suggested incomplete regeneration. The pathological changes were presumably the result of the long-term clinical course of VWF. PMID- 3353696 TI - Memory sequelae of solvent intoxication. AB - A retrospective study on a small group of female workers accidentally intoxicated by organic solvents (toluene and aliphatic hydrocarbons) evaluated complaints of residual memory impairment. Memory testing was first performed two months after the intoxication with a follow-up six months later to assess recovery. The workers showed normal patterns of performance on tests of learning and short-term and longer-term memory, but marked difficulties were observed when attention had to be allocated between two resource-competing tasks. As there was no evidence of recovery by the follow-up session, the results indicate that solvent intoxication can cause neuropsychological sequelae lasting for over eight months. PMID- 3353695 TI - Prospective clinical and psychometric investigation of patients with chronic toxic encephalopathy induced by solvents. AB - Sixty-two patients with chronic toxic encephalopathy diagnosed in 1976-1981 were considered for reexamination in 1983-1984. Thirteen were found to have other diseases that might contribute to brain dysfunction. Seventeen were unwilling or unable to participate. The final group consisted of 32 men 33 to 63 (median 55) years of age who were physically and psychometrically reexamined with the same methods used in the initial investigation. The interval between the first and present examination was 21-88 (median 48) months, and exposure to solvents had ceased. The subjects reported some improvement in their neurasthenic problems. In particular they suffered less from fatigue, headache, and dizziness. When diagnosed they had an average of seven out of ten typical neurasthenic symptoms included in the toxic encephalopathy syndrome. At the time of the follow-up the mean number of symptoms had decreased significantly to five. The psychometric retesting showed significant deterioration in verbal memory, improvement in visual memory, and unchanged results on the other tests. In conclusion, these toxic encephalopathy patients improved subjectively when exposure stopped. Psychometrically they performed very close to the initial testing, which excluded progressive brain disease or subacute pharmacological solvent intoxication. PMID- 3353697 TI - Comment on the interpretation of Jappinen et al concerning increased incidence among board mill workers. PMID- 3353698 TI - Fixing NIH: the 110% solution. PMID- 3353699 TI - Game depletion hypothesis of amazonian adaptation: data from a native community. AB - The low population densities and impermanent settlements of Amazonian Indians are often interpreted as adaptations to a fauna that offers limited protein resources and is rapidly depleted by hunting. Data spanning the 10-year life cycle of one northwestern Amazonian settlement show that variations in hunt yields result from temporal variations in peccary (Tayassu pecari and T. tajacu) kills that appear extrinsic to native population size. After 10 years, hunting success remained high and the kill rates for most prey did not suggest depletion. An array of environmental factors accounts for the incipient settlement relocation observed. PMID- 3353700 TI - HIV infection in the laboratory. PMID- 3353701 TI - Primate research and "psychological well-being". AB - In Mark Crawford's News & Comment article "Superconductor funds flat" (4 Mar., p. 1089), Robert J. Birgeneau was reported to have had his grant cut to $4.4 million. That National Science Foundation grant actually covers the Massachusetts Institute of Technology's Materials Research Laboratory and supports 40 faculty members. Birgeneau's personal grant was reduced from $125,000 in 1987 to $122,000 for this year. PMID- 3353703 TI - Institutes proposed for deafness, rehabilitation. PMID- 3353704 TI - It matters how you slice the pie. PMID- 3353702 TI - Hammer seeks $1 billion to cure cancer. PMID- 3353705 TI - Kennedy suggests NIH foundation. PMID- 3353706 TI - EPA bars use of Nazi data. PMID- 3353707 TI - Diet and health in China. PMID- 3353708 TI - The nasotemporal division in primate retina: the neural bases of macular sparing and splitting. AB - In primates, each hemisphere contains a representation of the contralateral visual hemifield; unilateral damage to the visual pathways results in loss of vision in half of the visual field. Apparently similar severe, unilateral lesions to the central visual pathways can result in two qualitatively different central visual field defects termed macular sparing and macular splitting. In macular sparing a 2 degrees to 3 degrees region around the fovea is spared from the effects of unilateral damage to the visual pathways. In macular splitting there is no such spared region and the scotoma produced by unilateral brain damage bisects the fovea. The patterns of decussation of the different classes of retinal ganglion cells in both New World (Saimiri sciureus) and Old World (Macaca fascicularis) monkeys have been determined by horseradish peroxidase injection. In both species the distributions of ipsilaterally and contralaterally projecting ganglion cells in the central retina are different from those in other mammals and suggest neural bases for macular sparing and splitting, respectively. PMID- 3353709 TI - Molecular basis for the influence of muscle length on myocardial performance. AB - According to Starling's law of the heart, the force of contraction during the ejection of blood is a function of the end-diastolic volume. To seek the molecular explanation of this effect, a study was made of the effects of length on Ca2+ sensitivity during tension development by isolated demembranated cardiac muscle in which the cardiac form of troponin C was substituted with skeletal troponin C. The results of troponin C exchange were compared at sarcomere lengths of 1.9 and 2.4 micrometers. Enhancement of the myocardial performance at the stretched length was greatly suppressed with the skeletal troponin C compared with the cardiac troponin C. Thus the troponin C subunit of the troponin complex that regulates the activation of actin filaments has intrinsic molecular properties that influence the length-induced autoregulation of myocardial performance and may be a basis for Starling's law of the heart. PMID- 3353710 TI - DNA looping. PMID- 3353712 TI - A Soviet human genome program? PMID- 3353711 TI - Biowarfare lab faces mounting opposition. PMID- 3353713 TI - Biological bases of childhood shyness. AB - The initial behavioral reaction to unfamiliar events is a distinctive source of intraspecific variation in humans and other animals. Two longitudinal studies of 2-year-old children who were extreme in the display of either behavioral restraint or spontaneity in unfamiliar contexts revealed that by 7 years of age a majority of the restrained group were quiet and socially avoidant with unfamiliar children and adults whereas a majority of the more spontaneous children were talkative and interactive. The group differences in peripheral physiological reactions suggest that inherited variation in the threshold of arousal in selected limbic sites may contribute to shyness in childhood and even extreme degrees of social avoidance in adults. PMID- 3353714 TI - Multiplex DNA sequencing. AB - The increasing demand for DNA sequences can be met by replacement of each DNA sample in a device with a mixture of N samples so that the normal throughput is increased by a factor of N. Such a method is described. In order to separate the sequence information at the end of the processing, the DNA molecules of interest are ligated to a set of oligonucleotide "tags" at the beginning. The tagged DNA molecules are pooled, amplified, and chemically fragmented in 96-well plates. The resulting reaction products are fractionated by size on sequencing gels and transferred to nylon membranes. These membranes are then probed as many times as there are types of tags in the original pools, producing, in each cycle of probing, autoradiographs similar to those from standard DNA sequencing methods. Thus, each reaction and gel yields a quantity of data equivalent to that obtained from conventional reactions and gels multiplied by the number of probes used. To date, even after 50 successive probings, the original signal strength and the image quality are retained, an indication that the upper limit for the number of reprobings may be considerably higher. PMID- 3353715 TI - Tertiary structure is a principal determinant to protein deamidation. AB - The protein deamidation process involves the conversion of the amide side-chain moieties of asparagine and glutamine residues to carboxyl groups. This conversion is an unusual form of protein modification in that it requires catalysis by an intramolecular reaction where both the substrate (asparagine and glutamine side chains) and "catalytic site" (the peptide nitrogen of the succeeding residue) are constituents of several consecutive residues along the polypeptide chain. The stereochemical factors governing this process were studied with a data base derived from the neutron crystallographic structure of trypsin from which amide groups and oxygen can be unambiguously differentiated because of their different neutron scattering properties. The neutron structure allowed for the direct determination of those residues that were deamidated; 3 of 13 asparagine residues were found to be modified. These modified residues were clearly distinguished by a distinct local conformation and hydrogen-bonding structure in contrast to those observed for the other asparagine residues. No correlation was found between preference to deamidate and the chemical character of residues flanking the site, as had been proposed from previous peptide studies. PMID- 3353716 TI - Electric field x-ray scattering measurements on tobacco mosaic virus. AB - The feasibility of electric field x-ray solution scattering with biological macromolecules was investigated. Electric field pulses (1.25 to 5.5 kilovolts per centimeter) were used to orient tobacco mosaic virus in solution (4.5 milligrams per milliliter). The x-ray scattering is characteristic of isolated oriented particles. The molecular orientation and its field-free decay were monitored with a time resolution of 2 milliseconds by means of synchrotron radiation and a multiwire proportional area detector. The method should also be applicable to synthetic polymers and inorganic colloids. PMID- 3353718 TI - The protein folding problem. PMID- 3353717 TI - A previously undetected MHC gene with an unusual periodic structure. AB - The major histocompatibility complex is a chromosomal segment embodying several gene clusters among which those with immune functions are the best characterized. This region is suspected to host other as yet undetected genes whose characterization may shed light on the population genetics and evolution of the whole gene complex and thus on its unexplained character of marker locus for a number of diseases of nonimmune or unknown pathogenesis. A novel gene was identified that is transcribed in all tissues tested and is located in mouse and man between the CA and Bf genes of the H-2 and HLA complexes, respectively. From the nucleotide sequence, derived from liver complementary DNA clones, it is predicted that this novel single-copy gene encodes a 42-kilodalton polypeptide that bears no recognizable relation to the protein families known so far, but it displays striking hallmarks of natural selection. PMID- 3353719 TI - NIH drug tests. PMID- 3353720 TI - The Windscale legacy. PMID- 3353722 TI - Voodoo science. PMID- 3353721 TI - Breakthrough for education at NSF? PMID- 3353723 TI - Japanese views on science compared to U.S. attitudes. PMID- 3353724 TI - Duesberg gets his day in court. PMID- 3353725 TI - Three-dimensional solution structure of plastocyanin from the green alga Scenedesmus obliquus. AB - The solution conformation of plastocyanin from the green alga Scenedesmus obliquus has been determined from distance and dihedral angle constraints derived by nuclear magnetic resonance (NMR) spectroscopy. Structures were generated with distance geometry and restrained molecular dynamics calculations. A novel molecular replacement method was also used with the same NMR constraints to generate solution structures of S. obliquus plastocyanin from the x-ray structure of the homologous poplar protein. Scenedesmus obliquus plastocyanin in solution adopts a beta-barrel structure. The backbone conformation is well defined and is similar overall to that of poplar plastocyanin in the crystalline state. The distinctive acidic region of the higher plant plastocyanins, which functions as a binding site for electron transfer proteins and inorganic complexes, differs in both shape and charge in S. obliquus plastocyanin. PMID- 3353726 TI - Molecular cloning of human and rat complementary DNA encoding androgen receptors. AB - Complementary DNAs (cDNAs) encoding androgen receptors were obtained from human testis and rat ventral prostate cDNA libraries. The amino acid sequence deduced from the nucleotide sequences of the cDNAs indicated the presence of a cysteine rich DNA-binding domain that is highly conserved in all steroid receptors. The human cDNA was transcribed and the RNA product was translated in cell-free systems to yield a 76-kilodalton protein. The protein was immunoprecipitable by human autoimmune antibodies to the androgen receptor. The protein bound androgens specifically and with high affinity. PMID- 3353727 TI - Cloning of human androgen receptor complementary DNA and localization to the X chromosome. AB - The androgen receptor (AR) mediates the actions of male sex steroids. Human AR genomic DNA was cloned from a flow-sorted human X chromosome library by using a consensus nucleotide sequence from the DNA-binding domain of the family of nuclear receptors. The AR gene was localized on the human X chromosome between the centromere and q13. Cloned complementary DNA, selected with an AR-specific oligonucleotide probe, was expressed in monkey kidney (COS) cells and yielded a high-affinity androgen-binding protein with steroid-binding specificity corresponding to that of native AR. A predominant messenger RNA species of 9.6 kilobases was identified in human, rat, and mouse tissues known to contain AR and was undetectable in tissues lacking AR androgen-binding activity, including kidney and liver from androgen-insensitive mice. The deduced amino acid sequence of AR within the DNA-binding domain has highest sequence identity with the progesterone receptor. PMID- 3353728 TI - Increased attention enhances both behavioral and neuronal performance. AB - Single cells were recorded from cortical area V4 of two rhesus monkeys (Macaca mulatta) trained on a visual discrimination task with two levels of difficulty. Behavioral evidence indicated that the monkeys' discriminative abilities improved when the task was made more difficult. Correspondingly, neuronal responses to stimuli became larger and more selective in the difficult task. A control experiment demonstrated that changes in general arousal could not account for the effects of task difficulty on neuronal responses. It is concluded that increasing the amount of attention directed toward a stimulus can enhance the responsiveness and selectivity of the neurons that process it. PMID- 3353729 TI - The rationale for the development of antithrombotic, antimetastatic and fibrinolytic drugs: a mechanic point of view. PMID- 3353730 TI - Antimetastatic agents. II. Summary of the interactions of tumor cells with blood coagulation factors, platelets, fibrinolytic factors, and inflammatory cells and their soluble mediators: potential for therapeutic interventions. AB - Although not reviewed during this session of the Workshop, other reactions in the hemostatic pathways are relevant to tumor-host cell interactions, are potential targets for antimetastatic agents, and are therefore included in Figure 1 and Table 1. For example, elsewhere in this issue of Seminars Loskutoff reviews the recent evidence for the importance of naturally occurring plasminogen activator inhibitors in the regulation of fibrinolysis. Since tumor cells may contain both tissue plasminogen activator and a urokinase-like plasminogen activator, the balance between tumor-mediated fibrin formation and fibrinolysis becomes an important issue in assessing antimetastatic treatment protocols. The relationship of the fibrinolytic pathways to metastasis has been reviewed recently by Dano and colleagues. Clearly, no single therapeutic approach designed to inhibit only one of these complicated interactions between tumor cells and host defense mechanisms is likely to be successful. However, each of the pathways illustrated (Fig. 1) and each of the theoretical steps in the metastatic cascade (Table 1) must be considered in the design of new strategies for the use of antimetastatic agents. PMID- 3353731 TI - Pharmacokinetic studies of standard unfractionated heparin, and low molecular weight heparins in the rabbit. PMID- 3353732 TI - Effect of dietary lipids on arterial thrombus formation: rationale for the support of drug therapy by diet. PMID- 3353733 TI - [Indications and methodology of transfixation of large joints with the monofixation device]. PMID- 3353735 TI - [Incidence of accidents and prevention of injuries in windsurfing]. PMID- 3353734 TI - [Cholecystitis following polytrauma]. PMID- 3353737 TI - [The halo fixation device--possibilities for its use and dangers]. PMID- 3353736 TI - [Arthroscopy of the proximal wrist joint. Indications, technic and clinical results]. PMID- 3353738 TI - [Stress fracture in biomechanical changes of the arch of the foot]. PMID- 3353739 TI - [Late brachial plexus lesion following clavicular fracture]. PMID- 3353740 TI - Congenital hepatic fibrosis. PMID- 3353741 TI - The postoperative chest. PMID- 3353742 TI - Medical geography--selected papers from the 1986 Rutgers symposium. PMID- 3353743 TI - A geographic regression model for medical statistics. AB - A method for modeling geographic processes using census-type data is introduced in an analysis of male and female lung cancer mortality rates. The study area comprises the counties in those states which abut the Gulf of Mexico and the southeast Atlantic Coast of the United States. A spatially autoregressive model is used to estimate the strength of the univariate relationship between both the male and female lung cancer mortality rates in a country and in the respective lung cancer rates in the first to fifth order adjacent counties. The results show that male lung cancer exhibits spatial autocorrelation while female lung cancer does not, and that the female data exhibit a spatial trend while the male data do not. These findings suggest that factors which vary at the regional scale play a greater role in the etiology of female lung cancer and that factors that vary at the neighborhood scale play a greater role in the etiology of male lung cancer. PMID- 3353745 TI - Display of small-area variation in health-related data: a methodology using resistant statistics. AB - Health care planning requires characterization of the population to be served. Examination of available demographic and epidemiologic data is one early step in this process. However, aggregate data for the entire geographic area of concern often fail to reveal important differences among geographically defined sub populations--differences that influence the form an effective delivery system should take. We present a methodology based on exploratory data analysis (EDA) techniques that we have found useful in examining health-related data for our ambulatory care catchment area. Our examples use three population characteristics that have major implications for health care planning for the elderly: 1970-1980 change in population aged 65+; the percent of the population aged 65+ below poverty level; and the percent of single-person households among households with one or more persons aged 65+. With these data for the 25 municipalities of Middlesex County, New Jersey, we illustrate a two-step process: (1) the construction of stem-and-leaf displays that permit examination of a data distribution for asymmetry, concentrations around specific values, gaps in values, and outliers; and (2) the use of the median, the fourth-spread, and other information from the stem-and-leaf display in the systematic selection of data value classes to be given distinct shadings on a map of the selected geographic area. Discussion emphasizes the usefulness of graphic display of data in detecting similarities and unusual data values. Comparison of maps based on the EDA techniques and maps based on several traditional methods of value classing for the same data illustrates the influence of classing choices on the interpretation of cartographic displays of health-related data. PMID- 3353744 TI - Carrier models for the simulation of Hodgkin's disease: a review with some extensions. AB - Epidemiologists have unearthed a good deal of both anecdotal and statistical evidence to suggest that Hodgkin's disease might be a transmissible entity. This paper critically reviews those findings which have led to the building of a single-region carrier model capable of making deterministic simulations for the temporal incidence of Hodgkin's disease. The results of fitting this model to the monthly incidence of the disease in Greater Manchester between 1962 and 1976 are discussed in relation to the plausibility of the equilibria associated with the more realistic solutions. In the light of this evaluation, the specification of the model is extended to include multi-region settings with more complex infective mechanisms. Finally, the improvements that accrue from adopting a stochastic modelling style are outlined. PMID- 3353746 TI - Regional development and seasonality of communicable diseases in rural Andhra Pradesh, India. AB - This paper explores the seasonality of morbidity due to communicable diseases in Guntur district in Andhra Pradesh, India. The district has been divided into development regions using cluster analysis. Seasonality of selected communicable diseases is then compared with the levels of development. It is shown that seasonality is most pronounced in the least developed region of the district. In the most developed region, seasonality of morbidity is low. The paper supports the general hypothesis that there is a decreased seasonality of illness as development takes place. PMID- 3353747 TI - An hierarchical location-allocation model for primary health care delivery in a developing area. AB - Location-allocation models can play an important role in making primary health care facilities more accessible to rural populations in the developing world. Traditional models, however, have failed to deal realistically with the fact that health care systems are hierarchical in nature, and that benefits and utilization decline with distance. In this paper, an hierarchical location-allocation model in which benefits accrue to facility level and decline exponentially with distance is presented as a possible approach to ameliorating problems of rural accessibility to health care in Third World settings. The model is subjected to sensitivity analysis with reference to data for Salcette Taluka, Goa, India. The analysis suggests that the traditional P-median model may be a much less appropriate solution to the problem than a simple strategy of locating facilities from the highest to the lowest level in centers of strictly decreasing population. PMID- 3353748 TI - A hybrid FLEET model for emergency medical service system design. AB - Covering models have been used to locate emergency services such as ambulance and fire protection systems. As an example, in the late seventies, an analysis of the Baltimore, Maryland fire protection system was conducted with the development and use of a covering model called the Facility Location and Equipment Emplacement Technique (FLEET). The FLEET model combined the location of fire stations with the allocation of primary and special service equipment to the stations. Further, in a recent study of Austin, Texas the ambulance system was restructured based on the use of a covering model. Covering models have also been extended to handle some of the special circumstances involved in emergency service systems. One example is the maximal expected coverage problem (MEXCLP). This paper presents a new covering model which utilizes both the special coverage structure of the MEXCLP and the simultaneous station location and equipment allocation of the FLEET model. Optimal solutions are found using linear and integer programming. Results of the model applied to several planning data sets (including a form of the Austin, Texas planning problem) demonstrate that more concentrated ambulance allocation patterns exist which may lead to easier dispatching, reduced facility costs, and better crew load balancing with little or no loss of service coverage. Tradeoff curves are presented which show that significant reductions in the number of dispatching sites (keeping the number of ambulances constant) can be made without any major changes in service level. PMID- 3353749 TI - Health education and baseline data: issues and strategies in nutrition campaigning. AB - A central problem for health education is the lack of baseline data concerning relevant issues such as smoking, alcohol consumption or nutrition. In the absence of this information there is little detailed knowledge of the public's habits or willingness to change those habits. Furthermore, the social context and spatial variation of these factors is unknown. Often the only way in which suitable information can be acquired is through social surveys. This paper uses a case study of a nutrition survey to outline a general framework for the collection of baseline data. The approach centres around postcode based data linkage. The effectiveness of the approach is considered and its shortcomings noted. PMID- 3353750 TI - Linking the geographical, the medical and the political in analysing health care delivery systems. AB - The models and methodologies used by medical geographers for analysing health care delivery systems are critically reviewed. As a result, it is argued that an intellectual cul-de-sac has been reached because of the lack of linkage in these models and methodologies that explicitly recognize the socio-cultural and political-economic influences in the environment, where the health care delivery system under study exists. Using the example of abortion services in Canada in general, and Ontario specifically for illustrative purposes, a general model for linking the geographical, the medical and the political aspects of health care delivery is proposed. PMID- 3353751 TI - What does distance matter? Leprosy control in West Nepal. AB - One of the major planks of leprosy control strategies is that distance from established treatment centres deters leprosy cases from seeking treatment. The integration of leprosy care with locally available primary health care services is therefore a common feature of leprosy control programmes. Within these guidelines, a National Leprosy Control Programme was established in Nepal in 1975, with intensive case-finding surveys and the provision of leprosy care in government basic health posts. A study of one district, Lamjung, in West Nepal suggests that far from being a deterrent, distance afforded welcome anonymity for leprosy cases anxious to disguise their diagnosis and thereby avoid the social ostracism which could result. Cases from ethnic groups in which the stigma of leprosy was high travelled farther for treatment. Gender differences in distance travelled suggest that women's mobility was restricted, but the local availability of care did not increase attendance for regular treatment. It is suggested that this was more the result of poor quality of care than fear of being known locally as a leprosy case. PMID- 3353752 TI - Privatising residential care for elderly people: the geography of developments in Devon, England. AB - The growth in numbers of very elderly people is becoming a trend in many Western societies. Often, these people may come to require some kind of assisted living environment. In Britain during the 1980s the overwhelming growth of residential accommodation has been in the private rather than the public sector. This has links with a number of other trends in health care and other sectors of the economy which are moving towards privatisation. The reasons for this are discussed and a case study of the county of Devon introduced. A survey of about one-quarter of all 450 homes in the county in mid-1984 revealed that they had important characteristics as small businesses. Countywide, a marked concentration of private residential homes has developed in some coastal 'holiday' locations. However, there have recently been changes in this pattern and growth of numbers of homes in some main towns also. There have been certain adverse reactions to the growth of homes and in a few areas, planning authorities have attempted to prevent the development of local concentrations of homes. This has been related to other policies elsewhere to prevent the concentration and ghettoisation of service-dependent groups. The nature and results of such planning policies are briefly considered. The paper addresses the overall questions of the type of care we wish to provide for our elderly people and whether privatisation of this aspect of health and welfare services is justified. This poses an important area of research for medical geographers interested in service delivery and aspects of equity in health care provision. PMID- 3353753 TI - Migration and morbidity: implications for geographical studies of disease. AB - Many studies have examined associations between the geographical patterns of disease and possible causal factors. Underlying such studies is the assumption that residence in an area can be equated with exposure to conditions that pertain there. Migration upsets this assumption. Using data on self-reported morbidity from the 1981 Census for Great Britain it is shown that the health status of migrants differs considerably from that of non-migrants. Young migrants, particularly those moving longer distances are relatively healthy. Area of net out-migration of this age group are therefore likely to become characterised by a less healthy population whereas the reverse will be true of areas of net in migration. Amongst older people migration tends to be selective of those in poor health moving shorter distances to avoid environmental health hazards or to be closer to medical care. This has the curious effect of increasing morbidity and mortality rates in areas with favourable environmental conditions and good medical services. Migration is therefore likely to be a significant source of error in geographically based studies of the association between disease and the environment. Sometimes the effect will be to obscure real environmental causes of disease. In other circumstances spurious association will be produced. These problems will be greatest for diseases with long latent periods which allow plenty of time for mobility of the population. Problems are also likely to increase with the growing mobility of the population. PMID- 3353754 TI - Time-space clustering of Vibrio cholerae 01 in Matlab, Bangladesh, 1970-1982. AB - Growing evidence for the existence of an aquatic reservoir of Vibrio cholerae has led some observers to postulate the existence of two distinct modes of disease transmission: primary and secondary. In primary transmission vibrios pass from the aquatic reservoir to humans via edible aquatic flora or fauna, or drinking water. Secondary transmission consists of faecal-oral transmission from person-to person and may spawn epidemics. Cholera outbreaks are particularly well documented for the Matlab area of Bangladesh, where a field station has been run since 1963, at which patients from a study population of nearly 200,000 are treated for diarrhoeal diseases and monitored in a longitudinal demographic surveillance system. This paper seeks to illuminate the process of secondary transmission by presenting preliminary results of an analysis of the time-space distribution of cholera cases in Matlab for the period 1970-1982. It is argued that the detection of time-space clusters of cases resulting from secondary transmission requires locational data below the level of the village, that is at the level of the bari, or patrilineally-related household group because this is where inter-personal contact is greatest. The mapping of the study area at the bari level is described briefly and it is argued that the proportion of all asymptomatic infections and cases which can be mapped is great enough to enable inferences about transmission processes to be drawn. Results of the analysis of time-space interaction using the Knox method are presented and provide some support for within-bari clustering of cases resulting from secondary transmission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353755 TI - Monitoring and predicting community mental health centre utilization in Auckland, New Zealand. AB - Deinstitutionalization of mental health care has been in progress in many countries for over a quarter of a century. A comprehensive and detailed literature has evolved focussing on this process and its implications for alternative forms of combatting the incidence of mental illness. Most notably, literature has concentrated on the need for community-based mental health services both to prevent hospitalization in the first place and to ease the return of the hospital patient into the outside environment. In this paper the evolution of such a community-based system in metropolitan Auckland, New Zealand is discussed. More specifically, the focus is on the utilization of four community-based centres, with a view to plan better growth or reduction of service provision. Two dimensions of centre use, spatial and sociodemographic, are analysed and incorporated into four predictive models that, with appropriate refinement, can be used to determine the likely level of centre use in unserviced parts of the metropolitan area. Distance of individuals from centre locations is shown to be a significant factor in affecting use for three suburban primary prevention and intervention centres, whilst distance is non-significant for an inner-city aftercare facility. Also, various combinations of socio-demographic variables, reflecting service-specific needs for specific groups in the population, are shown to contribute significantly to predicting centre use. The paper presents the results against a policy backdrop in New Zealand where community mental health services are very much experimental in nature. The results reaffirm the importance of community mental health care in fulfilling an important need in society that health care administrators should take seriously in future policy developments. PMID- 3353756 TI - Obstetric care in The Netherlands: regional differentiation in home delivery. AB - In this paper attention is focused on home delivery in the Netherlands, which still accounts for 36% of the total number of births delivered. Compared to countries with a similar level of socio-economic development, home delivery plays an important role within Dutch obstetric care. To understand this unique situation, one needs to have insight into the organization and structure of Dutch obstetric care which is described in the first part of this paper. In the second part of this paper regional differentiation in the relative importance of home delivery is described. Finally regression analysis is used in order to explain the observed regional pattern. A brief abstract from the vast amount of Dutch literature on the discussion between advocates and adversaries of home delivery is included in an appendix. PMID- 3353757 TI - The epidemiology of primary acute pancreatitis in Greater Nottingham: 1969-1983. AB - In most countries primary acute pancreatitis is a rare disease. However, its incidence has been increasing for several decades and many patients do not survive their first attack. During the 15 years (1969-83) 493 patients with the disease were admitted to Nottingham's two District General Hospitals. The geographical distribution of the disease within the study area was determined using 62 electoral wards and two patient cohorts namely 214 1969-76 admissions (1971 census base) and 279 1977-83 admissions (1981 census base). The incidence of the disease increased from 27 per annum to 40 per annum in the two cohorts. Most of the alcohol associated patients (18 first cohort: 38 second cohort) were young or middle aged males. For gallstone and 'non-gallstone' associated groups the incidence rose sharply with increasing age for both sexes. For both cohorts there were large statistically significant variations in the distribution of pancreatitis within the study area. Moreover, the spatial distribution was very similar for both cohorts with most of the highest rate wards clustering in a U shaped area east of the city centre. Investigation of environmental factors suggested that this high-rate area coincides with the region served by the Burton Joyce domestic drinking water supply. Examination of the residential histories of the 493 patients showed that 25.6% had moved home less than five years prior to their first attack. Analysis of these moves confirmed that many patients had moved to suburban areas from two major inner city housing renewal schemes located within the high-rate Burton Joyce water supply area. Re-calculation of incidence rates of pancreatitis by former address for the six water supply areas established that only the Burton Joyce area had significantly high numbers of cases for both cohorts. PMID- 3353759 TI - Worksite health promotion. PMID- 3353758 TI - The comparison of health care systems through regional analysis: the case of hospital admissions in Belgium and The Netherlands. AB - One of the problems in the international comparison of health care systems is the small number of units of analysis. Usually only a small number of systems is compared which makes cross-sectional statistical analysis impossible. The two obvious solutions to this problem--neither of which is generally feasible--are either to enlarge the number of systems being compared or to use time series on a small number of health care systems. Quite another solution is to study regional variations within and between a small number of systems. The number of regions has to be sufficiently large to make statistical analysis possible. This is the solution chosen in this article. The phenomenon which is central to our analysis is the number of hospital admissions per 1000 of the population. To explain variations in the hospital admission rate, it is hypothesized that there are a number of variables that have the same kind of influence on hospital admission rates in all western industrialized countries (such as the supply of hospital beds and the health status of the population). On the other hand there are determinants of regional variation in the number of admissions which either exert an influence dependent on the nature of the system, or are unique to a particular health care system. Concerning the first group of hypotheses (the general model), our analysis based on data for 1974 showed that the only variables to have a clear and equal influence on the regional variation in hospital admission rates in the Netherlands as well as in Belgium are the number of hospital beds per 1000 inhabitants and standardized mortality (an operationalization of the concept of health status). The influence of system-specific variables (the second group of hypotheses) has been analysed, taking the difference between the actual number of admissions and the number of admissions expected on the basis of the number of beds and mortality as the dependent variable. In the Netherlands, none of the variables appears to have a clear influence on the level of this ratio, whereas in Belgium there is a greater number of admissions than expected in regions with a higher birth-rate and a higher number of both general practitioners and specialists in the common disciplines (internal medicine, pediatrics, gynaecology) in relation to the total number of specialists. PMID- 3353760 TI - Changing health practices: the experience from a worksite health promotion project. AB - This paper uses data from an employee health promotion project for government employees to examine initial health practices and their relationship to social and demographic variables. It then uses data collected one year later to examine changes in health behaviors and to try to explain what types of people are most likely to undertake health behavior changes in a year, within the context of a worksite health promotion project. Most people in this sample of employees do make positive changes in health habits in at least one of the following areas: smoking, seatbelt usage, diet, exercise, alcohol usage. While a variety of different social and demographic variables are important in explaining initial differences in health practices, these same variables along with measures of personal efficacy and job stress are poor predictors of whether people change their health behavior over a year. Future research might usefully focus on more detailed collection of qualitative data to help understand what factors motivate people to change health behavior. Future survey approaches may then incorporate broader and more diverse categories of explanatory variables into regression models. PMID- 3353761 TI - Gender differences in worksite health promotion activities. AB - A model of intentional health-related behaviors was tested to predict men's and women's participation in six worksite health promotion programs. The model was best at predicting participation in programs that treat unhealthy conditions or behaviors. It was least successful at predicting participation in programs than can appeal to both those with 'health risks' and to health 'maximizers'. Women had higher rates of participation than men in three of the four 'treatment' programs, and they participated in more programs. In every program type, the factors that influence women's participation were different from those affecting men; and women with children showed different patterns of influence from women without children. The patterns of influence are consistent with two sources for women's greater concern with treating poor health: their nurturant role responsibilities, and a particular emphasis by the medical profession on women and women's concerns. PMID- 3353762 TI - The effects of a worksite health promotion program on the wives of fire fighters. AB - One method of increasing the cost-effectiveness of worksite health promotion programs is to develop programs that also have an impact on risk factors of family members and friends of the employees. In this study, 41 wives of fire fighters were interviewed concerning changes the fire fighters and they had made in their health habits--exercise, weight, and consumption of fats, fruits/vegetables, and cereal/whole grain breads--in the previous year. Thirty two were wives of fire fighters who had received a worksite health promotion program and nine were wives of fire fighters who had not yet received the program. Findings of our exploratory study strongly suggest that wives of fire fighters who received information were more aware of the program (93% vs 56%), had greater exposure to the written diet plan (72% vs 11%) and guide to high fat foods (72% vs 0%) than controls. Furthermore, the intervention led to changes in the fire fighters' health habits that were reported by the wives. No significant changes in the wives' health habits occurred as a result of the intervention, although the changes were in the predicted direction in every category; changes by the wives were, however, related to changes by fire fighters. Involvement of the fire fighters in the preparation of meals and sharing of information from the intervention program by the participant with the wife, were related to change in health habits of the wives.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3353763 TI - Health and fitness at work: a participants' perspective. AB - In the 1980s worksite health promotion or wellness programs have become more common in American corporations. Corporations see them as a way to control rising health care costs and to improve employee health. This paper examines participants' perspectives on participation in a health and fitness program, based on participant-observation and 35 in-depth interviews with members of one corporate program. Participants have a decided fitness-orientation (as opposed to a health-orientation), focusing on staying in shape and controlling weight. The consequences of this orientation for the promotion of health, the future of wellness programs, and the corporation are discussed. PMID- 3353764 TI - Workplace wellness participation and the becoming of self. AB - This paper provides a sociological examination of workplace wellness participation as a process that occurs in two stages or levels. The existential model of self provides the theoretical orientation for this examination, and data are presented from an ethnographic study of a large workplace wellness program. The first stage or level of participation involves the establishment of a sense of competence. Competence refers to the perceived ability to 'fit in' with the program, to master the often subtle skills required for membership in the class. Once a minimal sense of competence is established, the employee may decide to join by viewing participation either as an extension of a commitment to wellness, or as a vehicle for experimenting with or establishing a new style of self, the identity of a 'well person' so highly valued in contemporary western culture. The dynamics of workplace wellness participation illustrate a more general cultural trend towards health-as-accomplishment. PMID- 3353765 TI - [Individualization of materials for the change of dressings]. PMID- 3353766 TI - [Psychological and relational aspects of the terminal phase. To die and to watch dying]. PMID- 3353767 TI - [Abandonment, therapeutic persistence, euthanasia]. PMID- 3353768 TI - [Analysis of a case of care of pervasive pain]. PMID- 3353769 TI - [Relationship of assistance to the dying and to oncologic patients. November 1983 June 1987]. PMID- 3353770 TI - [Death with the Yoruba of Benin-Nigeria in black Africa]. PMID- 3353771 TI - [Making an active verb out of "dying"]. PMID- 3353772 TI - [A prison nurse in the penitentiary]. PMID- 3353774 TI - [The helping relationship]. PMID- 3353775 TI - [Physical dependency and primary care]. PMID- 3353773 TI - [Preparation and role of the nursing staff in a nursing school]. PMID- 3353776 TI - [Non MAO inhibiting non tricyclic antidepressive agents]. PMID- 3353777 TI - [Animal models of depression]. PMID- 3353778 TI - [Chronobiology of depression]. PMID- 3353779 TI - [Prescription of an antidepressive agent]. PMID- 3353780 TI - [Clinical evaluation of the effects of antidepressive agents]. PMID- 3353781 TI - [Dosage of tricyclic antidepressive agents. Monitoring and guide to therapy]. PMID- 3353783 TI - [Depressive disorder; disease of the century]. PMID- 3353782 TI - [Mechanism of action of antidepressant agents]. PMID- 3353784 TI - [Various aspects of the activities of city specialists]. PMID- 3353785 TI - [Certification of work sites in the hospital]. PMID- 3353787 TI - [Program for improving public health]. PMID- 3353786 TI - [Planning and organization of epidemiological research into the health status of the population in relation to air pollution]. PMID- 3353788 TI - [Prophylactic methods in oncological urology]. PMID- 3353789 TI - [Problems in teaching a course on Soviet law in medical schools]. PMID- 3353790 TI - [Cardiovascular and cancer diseases in the population of the developing countries of Africa]. PMID- 3353791 TI - [Planning the utilization of hospital bed capacity for medical first aid]. PMID- 3353792 TI - [Unusual complications of implanted artificial heart valves]. PMID- 3353793 TI - [Surgical treatment of cardiac myxoma]. PMID- 3353794 TI - [Chylothorax--problems of therapy]. PMID- 3353795 TI - [Problems in thoracic surgery in Czechoslovakia]. PMID- 3353796 TI - [Surgical possibilities of hyperlipidemia therapy]. PMID- 3353797 TI - [Retroperitoneal rupture of the duodenum in a 9-year-old boy]. PMID- 3353798 TI - [Cystic degeneration of the adventitia of the popliteal artery]. PMID- 3353799 TI - [Aorto-enteral fistulae]. PMID- 3353800 TI - Morbidity in the elderly--could dietary changes help? PMID- 3353801 TI - Aspirin and myocardial infarction. PMID- 3353802 TI - Mesothelioma is a fibre-specific tumour. PMID- 3353803 TI - Disease outbreak investigations--objectives, methods and importance. AB - In South Africa approximately 100 disease outbreaks or epidemics requiring investigation and control can be anticipated each year. Outbreak investigations play a critical role in determining effective disease control strategies. The application of modern epidemiological methods to the study of disease outbreaks is discussed and problem-solving methodology, which has similarities to the approach used in clinical diagnostics, described. These methods were applied to the investigation of an outbreak of Legionnaire's disease at a Johannesburg teaching hospital. PMID- 3353804 TI - Adolescent health problems--can paediatricians in the RSA cope? AB - Paediatricians are probably the physicians best able to care for adolescents. However, in the RSA they tend to set the upper age limit of their patients at the early teens. This study compared the disease profile of paediatric medical admissions with that of adolescent medical admissions in a Third-World situation in order to determine whether the training programme for local specialist paediatricians needed to be widened to ensure successful management of the older age group. In addition, the number of adolescent and paediatric medical admissions were compared to establish whether adolescent admissions formed a large enough group to justify changes in the specialist training curriculum. It was found that adolescents were admitted to medical wards in significant numbers. Their disease profile differed markedly from that of patients admitted to the paediatric wards. It was evident that additions to the curriculum would be necessary before paediatricians in the RSA could manage adolescents with expertise and confidence. PMID- 3353805 TI - Neonatal screening for congenital hypothyroidism. A decade's review, including South Africa. AB - Since its introduction in 1974, neonatal screening for congenital hypothyroidism has been very extensively conducted world-wide. It is the commonest disorder found in all neonatal screening programmes, occurring in 1:3,000-8,000 births. Laboratory testing for thyroid function within the first 5 days after birth identifies this disorder weeks to months before clinical symptoms become evident and the clinical diagnosis is made. A screening programme in Pretoria (February 1981- October 1986) has identified 11 hypothyroid neonates in some 45,577 infants tested. Internationally, there is now a 10-year experience (and a follow-up for a number of programmes) of neonatal hypothyroidism diagnosed by laboratory screening tests and treated within weeks of birth. There is conclusive evidence that the physical and mental development of these children is within, or approaches to a great degree, normal limits. PMID- 3353806 TI - Response of severe infantile diarrhoea to soya-based feeds. AB - Ongoing acute diarrhoea in infancy may respond to a change from a cows' milk to a soya-based formula. This is usually ascribed to the change in carbohydrate content of the feed but the ideal carbohydrate composition of the soya feed is uncertain. Twenty infants with severe watery diarrhoea persisting 2 days after initial rehydration and refeeding with a cows' milk formula were randomly allocated to one of two soya-based formulas. In one the carbohydrate was a mixture of sucrose and glucose polymers and in the other all the carbohydrate glucose polymers. No advantage was noted for either formula. Approximately 50% of each group responded to dietary change. The prompt cessation of diarrhoea and the disappearance of evidence of carbohydrate malabsorption suggests the response is due to the removal of lactose from the diet. Those infants that did not respond had evidence of continuing carbohydrate malabsorption and were not simply lactose intolerant. The pathogenesis of this carbohydrate malabsorption and the possible relationship to small-bowel bacterial overgrowth requires further investigation. PMID- 3353807 TI - Epidemiological factors in acute infectious infantile diarrhoea in Cape Town. AB - The results of a year-long prospective study of the epidemiological factors associated with acute infectious infantile diarrhoea in Cape Town are reported. Many coloured infants had a low birth weight, which was a risk factor for subsequent malnutrition. The parents were young, often unmarried, had 1-3 children and below average living conditions. However, coloured parents were better educated and had smaller families than their black counterparts. The incidence of breast-feeding was low, especially in the coloured population group. Black families originated from a largely migrant population and generally came from a squalid environment and had a higher incidence of sibling deaths. A hypothesis is advanced: coloured infants with infectious diarrhoea come from a deprived subgroup of their community while black patients come from a society that is generally disadvantaged and impoverished. In both groups financial pressures exacerbate the situation. Priorities are an improvement in living conditions--particularly for the black community--and the promotion of breast feeding among coloured mothers. Oral rehydration programmes are advocated for both groups. PMID- 3353808 TI - Dagga-smoker's hand--a new physical sign? AB - The results of 103 medicolegal autopsies undertaken to detect the presence of cannabinoids in the urine are compared with stains on the hand supposedly suggestive of cannabis smoking using the 'bottleneck' technique. Experience with the EMIT d.a.u. (Enzyme Multiplied Immuno-Technique for drugs of abuse in the urine) cannabinoid assay system (Syva Corp., Palo Alto, California, USA) is discussed. PMID- 3353809 TI - Percutaneous transhepatic balloon dilatation of strictured hepaticojejunostomies. AB - Strictured hepaticojejunal anastomoses can be surgically repaired with excellent results. However, remedial surgery may be difficult or hazardous in some patients and percutaneous transhepatic balloon dilatation (PTHBD) may be used as an alternative. Three patients with complicated strictured hepaticojejunostomies have been managed with PTHBD with good short-term results. The procedure was safe, technically easy and associated with low morbidity. Although long-term efficacy is not proven, this method can be used to prepare patients for elective surgery or as a definitive procedure in patients who are poor surgical risks. PMID- 3353810 TI - In vitro determination of bone mineral content of the femur neck. Use of computed tomography. AB - An accurate method for the in vitro measurement of mineral content of femoral bone by means of computed tomography (CT) is presented. The bone mineral content (BMC) of the femoral head in patients with a subcapital fracture was determined and compared with that in patients with osteo-arthritis. There was a satisfactory standard curve and a highly significant relationship between the CT number (Hounsfield number) and a standard bone equivalent reference (K2HPO4) was obtained at two different energies (96 and 125 kV). The calculated error in the calibration procedure was less than 1,5% and the overall error of the method was 8,8%. The femoral BMC of patients in the fracture group was found to be substantially lower (P less than 0.001) than that in osteoarthritis. PMID- 3353811 TI - [Renal cell carcinoma with a spindle-cell element--sarcomatous or sarcomatoid?]. AB - In this study the light microscopic and electron microscopic findings in two renal cell carcinomas with spindle-cell elements are described. The ultrastructural features of the spindle-cell element of sarcomatoid renal cell carcinoma have previously been documented, namely pentalaminar desmosomes, basal lamina formation and intracytoplasmic lumina with microvilli. The electron microscopic findings in the 2 cases described here showed mesenchymal rather than epithelial differentiation. It would appear that some renal cell carcinomas with a spindle-cell element are true carcinosarcomas, rather than sarcomatoid renal cell carcinoma. PMID- 3353812 TI - Epidermolysis bullosa misdiagnosed as child abuse. A report of 3 cases. AB - Three cases of epidermolysis bullosa are reported; the typical skin lesions were misdiagnosed as non-accidental injury to the children. Awareness of the manifestations of this uncommon genodermatosis, as well as the wearing of identifying Medic Alert discs, should prevent this inappropriate diagnostic stigmatization. PMID- 3353813 TI - Fatal head injuries in bicycling. PMID- 3353814 TI - Unusual rupture of a flexor profundus tendon with a gunshot wound. PMID- 3353815 TI - Artificial saliva for xerostomia. PMID- 3353816 TI - Melatonin in human semen. PMID- 3353817 TI - [Hidden complications of bilharzia]. PMID- 3353818 TI - [Flours]. PMID- 3353820 TI - [Postnatal examination]. PMID- 3353819 TI - [The pathologic puerperium]. PMID- 3353821 TI - [Postpartum kinesitherapy: importance and principles]. PMID- 3353822 TI - [Psychological aspects of the puerperium]. PMID- 3353823 TI - [Postpartum contraception and sex life during the puerperium]. PMID- 3353824 TI - [Endometritis. Case report]. PMID- 3353825 TI - [Bronchiolitis of the newborn and the young child. Nursing record]. PMID- 3353826 TI - [Physiology of the puerperium]. PMID- 3353827 TI - [The normal puerperium]. PMID- 3353828 TI - Cyclosporin A stimulates proliferation of the liver cells after partial hepatectomy in rats. AB - The effects of cyclosporin A (CyA) upon regeneration of the liver were studied in rats after partial hepatectomy. In group 1, a standard two-thirds hepatectomy was performed. In group 2, CyA, a dose of 10 milligrams per kilogram, was given orally one day prior to, on the day of the operation and 24 hours after hepatectomy. The liver weight restoration, histologic findings and mitotic activities of remnant livers and serum levels of aminotransferase, albumin, total bilirubin and creatinine values were examined from 24 hours to ten days after the operation. Treatment with CyA resulted in an increase of the mitotic activities of the hepatocytes, which were twice as high as those in the control group. This phenomenon coincided well with the regenerative rate of remnant livers, histologic factors, albumin synthesis and other biochemical parameters. Our results indicate that CyA has a stimulatory effect upon liver cell proliferation after partial hepatectomy in rats. The augmentative effect of CyA on liver regeneration is discussed. PMID- 3353829 TI - Special problems after iatrogenic vascular injuries. AB - Iatrogenic vascular injuries occurring at our institution were reviewed and several special problems not previously well described were found. These include carotid and femoral pseudoaneurysms, occult hemorrhage and knotting of the angiographic catheter. These problems are exemplified in four patient reports to illustrate how appropriate planning of operative approach and adherence to vascular surgical principles can optimize results. PMID- 3353830 TI - Primary hyperparathyroidism. AB - An experience with 316 patients operated upon with a presumptive diagnosis of primary hyperparathyroidism is presented. Of the 316 patients, 291 (92.1 per cent) were cured after the initial cervical exploration without using any technique for preoperative localization of parathyroid tissue. Persistent and recurrent hyperparathyroidism occurred in 4.0 and 3.7 per cent, respectively. The success rate for secondary operations (cervical and mediastinal) was 82 per cent. Permanent unilateral vocal cord paralysis occurred in three patients and persistent symptomatic hypercalcemia occurred in another two. Twelve (4 per cent) of the patients had hyperparathyroid crisis and five (1.8 per cent) had carcinoma of the parathyroid gland. The mean follow-up time was six years. Removal of a single macroscopically enlarged gland, if the other glands are normal, is all that needs to be done in most instances. Subtotal parathyroidectomy should be preserved for those patients who have diffuse glandular hyperplasia. PMID- 3353831 TI - Elevated levels of 6-keto-prostaglandin-F1a from a lower extremity during external pneumatic compression. AB - The synthesis of either fibrinolytic serine proteases or platelet inhibitory ecosonoids by the intact endothelial cell may limit thrombus development. In a preliminary study from this laboratory, an elevation in the level of 6-Keto prostaglandin-F1a, the stable metabolite of prostacyclin (PGI2) was demonstrated in femoral vein plasma obtained during surgical treatment from an extremity undergoing external pneumatic compression. Simultaneously, no elevations in thromboxane B2, the stable metabolite of thromboxane A2, were observed. The present study is an inclusive prospective series of 26 patients. A single pneumatic compression stocking was applied to the left limb in patients who underwent an operation under general anesthesia. Base line venous samples (3 milliliters) were obtained from the femoral vein on the experimental side and the control contralateral side, as well as from the upper limb. Additional samples were drawn at 30 and 60 minutes after the onset of compression. Nine samples per patient (234 total) were analyzed for 6-Keto-prostaglandin-F1a by competitive binding radioimmunoassay in duplicate in a single blind manner. Base line values for the upper limb, right leg and left leg were 0.08 + 0.01 nanogram per milliliter; 0.14 + 0.03 nanogram per milliliter, and 0.13 + 0.02 nanogram per milliliter, respectively (no statistical difference). By 60 minutes of compression, control samples increased to 0.40 + 0.07 nanogram per milliliter (right leg) and 0.42 + 0.08 nanogram per milliliter (upper limb) while the experimental leg increased to 0.71 + 0.13 nanogram per milliliter (p less than 0.05 versus right leg, p less than 0.005 versus upper limb). There was no statistical difference at 60 minutes between the men and women. PMID- 3353832 TI - Carcinoma of the duodenum. AB - Primary carcinoma of the duodenum is an uncommon tumor of the gastrointestinal tract. We reviewed the histories of ten patients seen between 1976 and 1986. Some of the patients with tumors in the second part of the duodenum presented with clinically evident jaundice. The symptom complex of all other patients was compatible with many benign diseases and made the diagnosis difficult. At laparotomy, seven patients had resectable disease. Two patients had advanced disease so that no curative resection could be done. In one patient, a resection was technically impossible. A modified Whipple procedure (in which the pylorus is saved) is the method of choice for tumors of the second part of the duodenum. We perform a segmental resection for other tumors. In five patients, there was no involvement of the lymph nodes and these patients are well--two more than 30 months postoperatively and one patient almost ten years postoperatively. In two patients, one or more lymph nodes were involved, but they are still well 30 months postoperatively. As the prognosis of carcinoma of the duodenum, once metastasized, is poor, a greater awareness of the possibility of a duodenal tumor must accompany aggressive diagnostic and surgical procedures. That will be the only way to a higher percentage of cures. PMID- 3353833 TI - The peel away introducer for the peritoneal limb of peritoneal venous shunt placement. PMID- 3353834 TI - A clampless method of rectal division during anterior resection. PMID- 3353835 TI - Surgical intubation by a new biliary endoprosthesis. PMID- 3353836 TI - A new operating proctoscope designed for use in rectal anastomosis by stapling techniques. PMID- 3353837 TI - The finger fracture technique in the fat laden mesentery. AB - A technique for easy and bloodless dissection of fat laden intestinal mesentery, both small and large, has been described. This technique can also facilitate Roux en-Y reconstruction in the obese patient. PMID- 3353838 TI - Fusiform intracranial aneurysms. Clinicopathologic features. AB - Seven fusiform aneurysms were found at autopsy in five patients (two males and three females) over a 13-year period. The subjects were between 56 and 65 years of age. The basilar trunk was the most frequent site. Four aneurysms were of giant proportions and contained laminated thrombi. Subarachnoid hemorrhage occurred in four patients. Microscopic examination of the aneurysm walls revealed atheromatous degeneration, focal wall attenuation, mural hemorrhage, rupture, and acute and chronic inflammatory cell infiltration. These findings suggest that rupture is not rare and that atherosclerosis is but one mechanism in the pathogenesis of these lesions. PMID- 3353839 TI - Ependymomas: a clinicopathologic study. AB - Since 1924, when ependymomas were first classified as a distinctive glial neoplasm by Bailey, much has been published concerning these tumors, but there are important points of interest that are still not clear. In order to study more fully the clinical and pathologic characteristics of the ependymoma, we identified 62 patients with histologically proven neoplasms. Twenty-two were supratentorial, 21 were infratentorial, and 19 were intramedullary spinal cord tumors. These groups had mean ages of 17, 7, and 41 years, respectively, at the time of first symptoms. The presenting and accompanying symptoms were related to location and included headaches, nausea, visual changes, hemiparesis, and neck, back, and radicular pain. Neurological signs included papilledema, nystagmus, gait disturbance, cranial nerve palsies, altered mental status, paraparesis, and sensory dysfunction. Radiologic modalities of particular importance included computed tomography and myelography. Surgery and radiation therapy were the primary treatment modalities with median survival times from first symptoms being 92, 36, and 117 months for the above groups, respectively. Based on computer generated survival curves, several characteristics significantly affected survival. These included tumor site, age, and neuraxis metastases. In patients with supratentorial tumors, cranial nerve palsies, microcystic changes, and mitotic figures were important, while in patients with infratentorial tumors, widened sutures, increased head circumference, age, epithelial features, and subependymal features significantly affected survival. Patients who had complete gross resection of a spinal cord tumor had no recurrences or mortality. PMID- 3353840 TI - Effect of nimodipine-associated hypotension on recovery from acute spinal cord injury in cats. AB - The effect of nimodipine on acute spinal cord trauma was studied in cats. Spinal evoked responses (SERs) were abolished after weight drop injury of 100 g-cm. All control animals showed spontaneous recovery of spinal cord function as measured by SERs. Treatment with a moderate intravenous dose of nimodipine resulted in a 32% drop in systemic blood pressure and delay in or failure of spinal cord recovery. We concluded that in this model, nimodipine treatment had deleterious effect on the spinal cord recovery due to the significant associated hypotension. It is likely that marked hypotension in the case of traumatic loss of autoregulation overrides the expected nimodipine-related increase in spinal cord blood flow with resultant additional ischemic damage. PMID- 3353841 TI - Three-quarter prone approach to the pineal-tentorial region. AB - A three-quarter prone, operative approach to the pineal region is described: the three-quarter prone, operated-side-down position. This approach avoids the disadvantages of the approaches from other directions to this region and provides a comfortable position for the surgeon and assistant, minimal retraction of the parietal-occipital lobe, and access to the third ventricle, pineal region, midbrain, and superior vermis. PMID- 3353842 TI - Disappearance of quadriparesis due to a huge cervicothoracic aneurysmal bone cyst. AB - A young man who had suffered from rheumatoid arthritis developed a huge cervicothoracic aneurysmal bone cyst and progressive quadriparesis. Complete recovery occurred after "incomplete therapy," which consisted of an open biopsy and a small dose of irradiation. This tumor was observed and characterized as a blood-filled cyst excavated from the bone. Because of the controversy in the literature over the benefit of surgery vs. irradiation, this report emphasizes the fact that even "partial" treatment may beneficially affect this tumor. PMID- 3353843 TI - Percutaneous diskectomy in the treatment of pediatric lumbar disk disease. AB - Intervertebral lumbar disk herniation in children and adolescents is rare. The incidence varies between 0.8% and 3.8% of all disks treated surgically. The uncertainty concerning operative or conservative treatment of this rare clinical entity has led to considering the use of atraumatic techniques, such as chemonucleolysis or percutaneous diskectomy. We report the unusual case of an 11 year-old girl with herniated disk at the L4-5 level treated by percutaneous diskectomy. This is, to our knowledge, the first case of a child treated by this technique. The technical simplicity, the minimal trauma it causes, and the excellent clinical result show that percutaneous diskectomy is a reasonable therapeutic alternative in the treatment of juvenile disks. PMID- 3353844 TI - Primary chromoblastomycosis of the medulla oblongata: complication of heroin addiction. AB - A 20-year-old male heroin addict had a sudden onset of progressive medullary dysfunction and died within 12 days. Postmortem examination disclosed mycotic granulomas due to primary chromoblastomycosis strictly limited to the medulla oblongata and adjacent leptomeninges. Similar lesions were absent outside the central nervous system. Such pathologic lesions related to narcotic addiction have not been reported previously. PMID- 3353845 TI - Pituitary apoplexy with intracerebral hemorrhage simulating rupture of an anterior cerebral artery aneurysm. AB - Pituitary apoplexy presenting with intracerebral hemorrhage into the left frontal lobe and lateral ventricle, simulating an anterior cerebral artery aneurysm rupture, is reported. No other cases of intracerebral hemorrhage caused by pituitary apoplexy have been found in a review of the English literature. PMID- 3353846 TI - Intramedullary subependymoma of the cervical spinal cord. AB - The authors report a rare case of intramedullary subependymoma of the spinal cord. The case is discussed and a review of the literature is presented. PMID- 3353847 TI - Disappearance of a tumor shadow fed by the tentorial artery. PMID- 3353848 TI - A view from the center. A former division chief's perspective on being a megadepartmental chairman. AB - Upon completing his sixth year as chairman of a large department of surgery in a major United States medical school, the author, a neurosurgical chief for 32 years, reflects upon the goals of departmental stewardship. The charges and challenges to any chairman of a multispecialty department are sampled from the perspective of personal experience. The general message could be interpreted as a call to service and a job description. PMID- 3353849 TI - The Peter Principle. PMID- 3353850 TI - Ethics corner. Mandatory retirement: convoluted euthanasia? PMID- 3353851 TI - [Cervical lymph node metastases from an unknown primary tumor]. AB - From 1978 through August 1986, 32 patients with lymph node metastases of the neck and unknown primary tumor were treated at the Radiotherapeutic Hospital of the University Erlangen-Nurnberg. Most of the cases were large metastases from squamous cell carcinomas or anaplastic carcinomas. The patients were treated by surgery and postsurgical radiotherapy or radiotherapy alone. In nearly all patients the target volume comprised both sides of the neck including the median structures as well as the base of the tongue and the nasopharynx. A dose of at least 50 Gy was aimed at, which was given within five weeks by individual doses of 2 Gy each. The survival at three years is 70% and at five years 52%. Out of twenty patients irradiated with more than 50 Gy following lymph node extirpation or radical excision of the lymph nodes of the neck, sixteen are tumor-free. The five year survival of this group is 80%. The results of radiotherapy alone are unsatisfactory, because only two out of nine patients are alive with follow-up periods of less than one year. Two primary tumors were found after the end of treatment. Both were situated within the ORL areas beyond the ancient irradiation fields, and both were developed by patients who at first had only been treated by local irradiation. Half of the patients with lymph node metastases of the neck and unknown primary tumors can be cured by complete tumor excision and postsurgical irradiation. The target volume of radiotherapy comprises both sides of the lymph drainage area of the neck as well as the mucous membranes of the ORL region including nasopharynx and base of the tongue. The dose is at least 50 Gy which is given after surgery with conventional fractionation. PMID- 3353852 TI - [An applicator for the implantation of I125 seeds for interstitial therapy of brain tumors]. AB - A compact magazine has been developed allowing a quick and easy implantation of I 125 seeds in interstitial therapy of intracranial tumors. The magazine is made of steel and has the shape of a right parallelepiped. One seed can be put each time into a movable insert. The magazine is connected to a normal application canula. It is easy to handle and contributes much to radioprotection. PMID- 3353853 TI - [Synchronization of tumor cells with 5-fluorouracil plus uracil and with vinblastine and irradiation of the synchronized cultures. A contribution to combined radio-chemotherapy]. AB - In this article, some arguments are put forward which support the conception of a combined radio-chemotherapy acting by a reversible inhibition of tumor cells with cytostatic drugs in a not cytocidal dose and the following selective killing by irradiation of the cells blocked in a radiosensitive phase. The two cytostatic drugs 5-fluorouracil (FU) and vinblastine (VLB), as inhibitors of DNA synthesis and mitosis, respectively, are tested in vitro both separately and combined in two tumor cell lines of the mouse, i.e. the Ehrlich ascites tumor and the sarcoma S 180. A cell-proliferative and, as far as possible, not cytocidal dose is used because of the inevitable side effects exerted by these drugs on normal tissues. A reversible synchronization of the ascites tumor is achieved even in the young mouse by FU in a dose of 15 ng to 500 ng (applied seven times every two hours), if the synchronization is controlled by applying the antimetabolite together with uracil in an equimolar concentration and then stimulating the growth of the cells inhibited during DNA synthesis by the administration of thymidine. The statistical analysis of dose-effect curves after X-ray irradiation shows an increased radiosensitivity of the synchronized cell population, provided that the optimum moment had been chosen for the irradiation. PMID- 3353854 TI - Choledochoduodenostomy for benign and malignant biliary tract diseases. AB - Although nonsurgical alternative treatments for primary or retained common bile duct stones--such as dissolution of gallstones with deoxycholic acids and, especially endoscopic papillotomy--have become available, choledochoduodenostomy (CDS) has been used with increasing frequency over the past decade, with extension of the indications for its use. We report our experience with side-to side CDS in 116 patients with benign (65 patients) and malignant (46 patients) biliary diseases. Even though the mean age of our patients with benign disease- patients who underwent urgent operations because of obstructive jaundice (74%), liver damage (approximately 60%), and other biliary complications--was 66.8 years, the perioperative mortality was 3.07% and the long-term follow-up results were excellent with no biliary complications. In regard to the controversy about the use of CDS in malignant biliary obstructions, our experience shows that none of the 42 patients had any complication due to malignant invasion of the stoma, and only one patient had ascending cholangitis; the perioperative mortality in this group was 8.6%. In our opinion, CDS is a relatively safe, definitive procedure for treatment of benign and malignant biliary diseases, with good long term results in high-risk, aged patients. PMID- 3353855 TI - Incidence of ureteral obstruction after aortic grafting: a prospective analysis. AB - In this prospective analysis of the incidence of ureteral obstruction after aortic bifurcation grafting, 120 patients were entered into the study: 19 were subsequently excluded for cause, and 101 patients were studied by isotope renography. The renographic findings were indicative for subsequent intravenous pyelography, which was performed in 26 patients. In two cases supplementary retrograde pyelograms were done. Two patients (2%) had ureteral obstruction related to the vascular prosthesis, and in one of these patients the process was bilateral. The lesions were asymptomatic in both patients. PMID- 3353856 TI - Thyroid and parathyroid surgery performed with patient under regional anesthesia. AB - Thyroid and parathyroid surgery is usually performed with the patient under general anesthesia; however, for selected patients regional anesthesia may be preferable. Between September 1977 and March 1986 regional anesthesia was used successfully as the sole anesthetic technique in 17 patients who underwent thyroid surgery and two patients who underwent parathyroid surgery. Procedures included two total thyroidectomies, 14 lobectomies or lobectomies with isthmusectomies, and one isthmusectomy. These 17 operations represent approximately 5% of the thyroid operations performed by the senior surgeon over the corresponding time. One patient underwent combined completion thyroidectomy and parathyroidectomy, and another patient underwent successful parathyroidectomy under regional anesthesia. In two additional patients, procedures could not be completed under regional anesthesia alone. In one of these two patients regional anesthesia appeared to effect a transient recurrent nerve paralysis. The indications for use of regional anesthesia have been primarily patient preference and associated cardiac or pulmonary disease. We now consider as contraindications to regional anesthesia patient apprehension about the technique, deafness, high spinal cord injury, recurrent laryngeal or phrenic nerve palsy, and allergy to local anesthesia. During this period, from 1977 to 1986, our administration of regional anesthesia has evolved from bilateral deep and superficial cervical plexus blocks to bilateral superficial blocks alone using bupivacaine with epinephrine, 1:200,000. PMID- 3353857 TI - Reactive hyperemia in patients with septic conditions. AB - In a prospective study microvascular reactivity was examined in 12 patients with septic conditions by means of the provocation of reactive hyperemia (RH) for evaluation of microcirculatory function. Data were compared with data from 10 nonseptic, postsurgical patients. At the time of the initial measurement, an adequate hyperemic response could be produced in all patients. In the further course of the disease, in nine of the 12 patients severe multiple organ failure developed. In spite of sufficient values for arterial blood pressure, oxygenation, and the clotting system, RH was absent in these patients (8 +/- 2 days after the initial measurement). Subsequently, seven of these nine patients died (4 +/- 2 days after the onset of microvascular nonreactivity). Until death, RH was absent in each patient, and at this time therapy-resistant hypoxemia, hypotension, and severe disturbances of the clotting system were present. In the two surviving patients RH was restored completely. These results indicate that (1) the septic state per se is not necessarily combined with impaired microvascular reactivity (rather, the absence of RH may be a sign of generally poor clinical conditions); (2) the absence of RH is not related to therapy resistant hypotension, hypoxia, and severe clotting disorders but precedes these changes; and (3) provocation of RH may be of clinical use for early detection of microcirculatory malfunction in high-risk patients. PMID- 3353858 TI - Heparin-induced thrombocytopenia and thromboembolism in the postoperative period. AB - The heparin-induced thrombocytopenia and thrombosis (HITT) syndrome is associated with hemorrhage as well as development of systemic thrombosis. A case is presented in which a posthepatectomy patient had probable heparin-induced thrombocytopenia complicated by venous thrombosis and pulmonary emboli after receiving low doses of heparin as line flushes. HITT is reviewed and factors related to its successful management in this postoperative patient are analyzed in detail. PMID- 3353859 TI - Spontaneous subclavian vein thrombosis: a successful combined approach of local thrombolytic therapy followed by first-rib resection. AB - In 17% to 74% of patients with subclavian vein thrombosis, conservative treatment or venous thrombectomy led to residual symptoms. To improve these results, a prospective study was started in patients with subclavian vein thrombosis who were treated with a combined approach of local thrombolytic therapy followed by a first-rib resection. From 1983 to 1987 five patients entered the protocol. Total lysis was achieved in all cases. In the follow-up period, phlebography and strain gauge plethysmography according to Whitney showed no recurrent thrombosis. All patients were able to resume their normal activities. PMID- 3353860 TI - Aortocolic fistula caused by an ingested chicken bone. AB - Primary aortocolic fistulas are a rare but lethal complication of aortic or iliac aneurysms. A case of fistula between a nonaneurysmal aortic bifurcation and sigmoid colon caused by an ingested chicken bone is presented. This cause of rectal bleeding, which has never been described, might have been suspected after careful examination of abdominal x-ray films. Surgical management included removal of the foreign body and primary repair of the colonic and aortic rent and appeared to be adequate. PMID- 3353861 TI - Anomalies of extrahepatic biliary duct and gallbladder associated with intestinal malrotation: a case report. AB - Knowledge of congenital anomalies in abdominal viscera is important for surgeons, if they are to treat such patients and solve their problems adequately. This article presents an unusual case of reversed rotation of the intestine associated with anomalies in the biliary tract and gallbladder. This patient underwent surgery because of a bleeding duodenal ulcer. During surgery the following viscera positions were detected: the gallbladder was located to the left of the round ligament, the choledochus was in front of the first portion of the duodenum, the small intestine was in the left portion of the abdomen, and the colon was exclusively at the right side of the abdomen. This reversed rotation is a rare condition, only occasionally reported in the literature. However, the simultaneous association with anomalies in the gallbladder position (in the left lobe) and the biliary tract (the choledochus located in front of the duodenum) makes this a case unlike any other described in the medical literature. PMID- 3353862 TI - Experimental induction of microphthalmia in the chick embryo with a single dose of cisplatin. AB - Chick embryos were injected on the fifth day of incubation with 75 ng cis diamminedichloroplatinum II (cisplatin) and killed at daily intervals. Bilateral microphthalmia appeared in 88% of the surviving embryos; the decrease in eye size was noticeable 2 or 3 days after injection. Coinciding with this, macroscopic, histological, and ultrastructural changes started to appear in the ciliary body: ciliary processes failed to form and the cells in the inner layer of the ciliary epithelium underwent degenerative changes. Changes in the retina appeared somewhat later. Despite the decreased growth rate of the whole eye the neural layer of the retina continued to grow rapidly; as a result, it formed numerous folds and acquired a glandular appearance. In the most severe cases the rapidly growing retina would invade the ciliary region and replace completely the degenerated inner layer of the ciliary epithelium. It has been shown by previous authors that intraocular pressure is a determinant of eye expansion and also that the secretion of water and ions by the ciliary epithelium is important for the maintenance of that intraocular pressure. On this basis, our results are interpreted as indicating that the primary lesion induced by cisplatin was in the ciliary epithelium and that microphthalmia was the consequence of decreased pressure. It is also concluded that the retinal changes were due to the fact that the retina continued to grow despite the lack of expansion of the eye as a whole. PMID- 3353863 TI - Prenatal ethanol weakens the efficacy of reinforcers for adult mice. AB - Pregnant C57BL/6cr mice were fed a liquid diet containing 20% of the total calories from either ethanol (E) or sucrose (S) for gestation days 5-17. Adult male and female (six of each from both prenatal-treatment groups) offspring were tested under various schedules of food reinforcement. The first phase was a test of fixed-ratio (FR) acquisition in which the required number of responses per unit of reinforcement was increased from 1 to 20 to 100. Prenatal ethanol exposure interacted with other factors to produce an acquisition deficit. The second phase involved responding under extinction (Ext). Under standard Ext procedures there were no prenatal-ethanol effects; however, when a conditioned reinforcer was superimposed on an FR 5, the E males did not increase their rates as much as the S males. Finally, under a multiple FR 5 DRO 15-sec (differential reinforcement-of-other-behavior) arrangement, prenatal-ethanol effects were found in each component. For the FR 5 component, prenatal ethanol eliminated the sex differences found in the S subjects. For the DRO 15-sec component, prenatal ethanol elevated response rates. The results indicate a general decreased efficacy of positive reinforcement in adult mice following prenatal ethanol exposure. PMID- 3353864 TI - Long-term changes in medication during pregnancy. AB - The Finnish Register of Congenital Malformations, established in 1963, rendered possible the study of changes in medication during pregnancy. The study consisted of 659 control mothers who had delivered a healthy child during the years 1964 1984. The data of this long-term follow-up study were collected by interviews at Maternal Health Care Centers after delivery and were completed by filed antenatal data. The results show a continuous decreasing trend in the usage of analgesics and tranquilizers but not in the usage of antiemetics, antibiotics, and vitamins. We believe that in Finland the publicity aimed at unnecessary medication during pregnancy has affected both the mothers and the health personnel. PMID- 3353865 TI - Brain changes in rats induced by prenatal injection of methylazoxymethanol. AB - Various doses (0, 1, 5, 10, 15, 20, or 25 mg/kg) of methylazoxymethanol acetate (MAM), a potent alkylating agent, were injected singly into pregnant rats intraperitoneally on day 15 of gestation. Relationships between brain weights and neurochemical changes in the cerebral hemispheres (CHs; cerebral cortex and subjacent white matter, hippocampus, amygdala) and remainder of the brain (BGDM; basal ganglia, diencephalon, and mesencephalon) were examined at 60 days of age in offspring; varying degrees of microencephaly were observed. Dose-dependent reductions in the weights of CH and BGDM were observed. Reductions in total DNA content positively correlated with decreases in brain weights also observed. Dose dependent elevations of noradrenaline (NA) and dopamine (DA) were observed in CH at MAM levels 10 mg/kg and above; dose-dependent elevations of 5 hydroxytryptamine (5-HT) were observed at 15 mg/kg and above; and in BGDM at 20 mg/kg and above dose-dependent elevations for NA and 5-HT were observed; dose dependent elevations at 15 mg/kg and above were observed for DA. Monoamine concentrations were negatively correlated with brain weights or total DNA contents. NA and DA concentrations increased to the extent of approximately 1.3 times of control at a time when an 18% loss of CH weight was noted in animals treated with 10 mg/kg MAM. It is suggested that the above variables might be appropriately sensitive neurochemical markers for detecting minor developmental anomalies in the brain. PMID- 3353866 TI - Heritable pulmonary lobation anomaly in the rat. AB - A new mutant gene which caused fusion of lung lobes was found in the Wistar rat. The genetic analysis revealed an autosomal recessive inheritance and the mutant gene was named fused pulmonary lobes (gene symbol: fpl). The right lung of the fpl/fpl homozygotes had fused lobes of varying degrees. The fpl/fpl homozygotes were semilethal at the neonatal stage and had externally visible associated malformations such as malocclusion of incisors, eyelid anomalies, and digit abnormalities in the fore- and hindlimbs with different incidences. These traits were considered to be caused by the pleiotropic effects of the fpl gene. PMID- 3353867 TI - Behavioural and developmental abnormalities in mouse trisomy 19: an animal model of mental retardation induced by chromosome imbalance. AB - Murine trisomy 19 (Ts19) can be regarded as a general model of human trisomies. It is the only autosomal trisomy in the mouse that survives the perinatal period. Therefore, it is the only animal model available for postnatal investigations of trisomy-specific mental retardation. To evaluate the extent of developmental retardation during the late-embryonic and fetal period of gestation, total body weight development was documented for 60 Ts19-fetuses and compared with that of 219 euploid in utero-mates. In addition, a postnatal study on body-weight development of 77 Ts19-neonates and 74 euploid littermates was performed starting on day 1 postpartum and continuing until spontaneous death or until day 22. Forty seven Ts19-individuals were further tested in nine behavioural test systems in order to determine their neurophysiological developmental profile. Findings were compared with age-dependent morphologic and physiologic parameters. The data obtained in the present study show a significant retardation of organ- and body weight development in Ts19-mice starting on day 14 of gestation. Retardation of physiological parameters is progressive and persists throughout the perinatal and postnatal periods. Furthermore, the trisomic individuals showed specific behavioural abnormalities. PMID- 3353868 TI - Umbilical vein variations: review of the literature and a case report of a persistent right umbilical vein. AB - A case of a ligamentum teres formed from an obliterated right umbilical vein is described. It passed to the right branch of the portal vein. The quadrate and left lobes of the liver were not separated by the usual fissure. Very few cases of anomalous umbilical veins or persistent right umbilical veins have been recorded. Of these, several have been recorded only in the umbilical cord, while in others the persistent right umbilical vein has been found intra-abdominally, in an extrahepatic position, and passing directly to the right atrium or to the inferior vena cava. Its presence is generally associated with severe congenital abnormalities, in contrast with the present case. In view of the high incidence of congenital defects associated with aberrant or accessory umbilical veins, when these are detected either in the umbilical cord or in the abdomen by umbilical phlebography, it is suggested that the patient should be carefully investigated for other congenital abnormalities. PMID- 3353869 TI - Television, children and the pediatrician: impact on health practices. PMID- 3353870 TI - Predictive values of low birth weight and preterm pregnancies. PMID- 3353871 TI - AIDS-related knowledge, attitudes and behavior in Travis County. PMID- 3353872 TI - Gastric restrictive surgery and obstructive sleep apnea. PMID- 3353873 TI - Abortion laws in Texas. PMID- 3353874 TI - Effects of breathing supplemental oxygen before progressive exercise in patients with chronic obstructive lung disease. AB - A study was carried out to determine whether supplemental oxygen before exercise would improve maximum exercise performance and relieve exertional dyspnoea in 20 patients with chronic obstructive lung disease (mean FEV1 0.79 l; forced vital capacity 2.30 l). Patients performed two progressive treadmill exercise tests to a symptom limited maximum, with at least 30 minutes rest between tests. They received compressed air or supplemental oxygen from nasal prongs for 10 minutes before exercise in a double blind randomised trial with a crossover design. Heart rate and breathlessness score on a visual analogue scale were compared between tests at 75% of the maximum distance walked in the compressed air test. The mean arterial oxygen saturation (SaO2) after oxygen (93%) was significantly higher than after compressed air (91%). There was no significant change, however, in maximum distance walked or maximum heart rate, or in the breathlessness score or heart rate at 75% of maximum distance walked. The study had a power of 93% for detecting an increase of 50 metres in maximum distance walked. There was an order effect, with better performance on the second test; but the magnitude of the difference was small. It is concluded that administration of supplemental oxygen sufficient to raise SaO2 above 90% for 10 minutes before exercise is unlikely to improve maximum exercise performance or breathlessness on exertion in patients with chronic obstructive lung disease. PMID- 3353875 TI - Use of nebulised saline and nebulised terbutaline as an adjunct to chest physiotherapy. AB - To determine whether sputum clearance is increased by using nebulised saline or terbutaline as an adjunct to chest physiotherapy, a radioaerosol method (using technetium-99m labelled human albumin millimicrospheres) was employed in eight patients with stable bronchiectasis on four occasions, for comparison of sputum clearance with four different regimens. These were: control, with the patient resting in an upright position; chest physiotherapy, by the forced expiration technique with postural drainage; and chest physiotherapy following five minutes' inhalation of either nebulised normal saline or nebulised terbutaline 5 mg. Use of both nebulised saline and nebulised terbutaline immediately before chest physiotherapy gave a significantly greater yield of sputum than did physiotherapy alone, and terbutaline also significantly increased radioaerosol clearance from the whole lung and from regions of interest. The mechanism is unclear, but this method may provide a simple way of increasing the efficacy of conventional chest physiotherapy. PMID- 3353876 TI - Platelet size in patients with chronic airflow obstruction with and without hypoxaemia. AB - Platelet size, expressed as mean platelet volume, was estimated in 35 patients with chronic airflow obstruction and a wide range of arterial oxygen tension (PaO2) values. In these patients there was a negative correlation between MPV and PaO2 (r = -0.70). Mean platelet volume was greater (9.41 (0.86) fl) in 20 patients with an arterial PaO2 of 8 kPa (60 mm Hg) or less than in 18 normal subjects (8.21 (0.63) fl; p less than 0.001). After 24 hours of supplemental oxygen treatment there was a small fall in mean platelet volume, from 9.47 (1.06) to 8.96 (0.8) fl (p less than 0.05) in 12 hypoxaemic patients (PaO2 breathing air less than or equal to 8 kPa) but no change in nine non-hypoxaemic patients. Larger platelets are considered to be haemostatically more active, leading to abnormal platelet function, which may contribute to the development of pulmonary vascular damage in chronic hypoxaemia. Supplemental oxygen may partially reverse these changes by modifying platelet size and activity. PMID- 3353877 TI - Cigarette smoke inhalation patterns and bronchial reactivity. AB - The manner in which a cigarette is smoked varies considerably between individuals and may be an important determinant of the altered bronchial reactivity observed in cigarette smokers. Twenty smokers were examined to determine the relationship between cigarette smoke inhalation patterns and bronchial reactivity. Inhalation patterns were measured non-invasively with a respiratory inductive plethysmograph and these were related to the provocative concentration of histamine that caused a 20% fall in FEV1 (PC20) and to the cough threshold for inhaled citric acid. Histamine PC20 values were inversely correlated with depth and rate of inhalation. Cough threshold was inversely correlated with greater cigarette consumption and with depth of inhalation. PMID- 3353878 TI - Massive haemoptysis caused by spontaneous rupture of a bronchial artery. PMID- 3353879 TI - Sarcoidosis possibly predisposing to disseminated histoplasmosis. PMID- 3353880 TI - Bilateral diaphragm paralysis and sleep apnoea without diurnal respiratory failure. PMID- 3353881 TI - Response and acclimatisation of symptomless smokers on changing to a low tar, low nicotine cigarette. PMID- 3353882 TI - Seasonal variation in non-specific bronchial reactivity: a study of wheat workers with a history of wheat associated asthma. AB - To investigate seasonal variation in non-specific bronchial reactivity in wheat workers, we carried out histamine inhalation tests in 29 workers (28 of them men) from a small farming community with symptoms of wheat associated asthma before, during and after the 1983-4 Australian wheat harvest season. Four were cigarette smokers, and the age range was 12-54 (mean (SD) 30 (10)) years. Twenty eight subjects were atopic (one positive skinprick test result in tests with 10 common antigens), 60% reacting to house dust mite and all to at least one of eight wheat antigens. Baseline spirometry gave normal results (mean FVC1 90% (SD 8%) predicted; FVC 91% (7%) predicted). Bronchial reactivity was tested by the method of Yan et al. The cumulative doses of histamine acid phosphate (up to 3.91 mumol) that caused a fall of 20% from baseline in FEV1 was determined (PD20) and expressed as the geometric mean. In the low exposure season, May 1983, nine subjects had a PD20 (mean 1.2, range 0.3-3.9 mumol). The number rose to 19 in the summer harvest season, December 1983 (mean 0.8, range 0.07-3.9 mumol) and returned to nine in the subsequent winter, July 1984 (mean 1.8, range 0.4-3.9 mumol). The change in the number of subjects with a PD20 was significant (p less than 0.01). Four additional subjects probably had increased bronchial reactivity in the harvest season: in two the post-saline FEV1 was too unstable to give them histamine challenge and in two the challenge was inadvertently discontinued prematurely. Baseline FEV1 and FVC fell by 8% between the first and second studies (p less than 0.001); values were intermediate in the third study (FEV1 3.74, 3.44, and 3.57; FVC 4.66, 4.28, and 4.41 litres respectively). Linear modelling analysis of log PD20, season, FEV1, FVC, age, seasonality of asthma symptoms and skin test data indicated that the harvest season was the only significant determinant of variation in log PD20. It is concluded that in these wheat workers there is a seasonal variation in bronchial reactivity that may reflect a response to allergens associated with grain. PMID- 3353883 TI - Quantitative features in the computed tomography of healthy lungs. AB - This study set out to determine whether quantitative features of lung computed tomography scans could be identified that would lead to a tightly defined normal range for use in assessing patients. Fourteen normal subjects with apparently healthy lungs were studied. A technique was developed for rapid and automatic extraction of lung field data from the computed tomography scans. The Hounsfield unit histograms were constructed and, when normalised for predicted lung volumes, shown to be consistent in shape for all the subjects. A three dimensional presentation of the data in the form of a "net plot" was devised, and from this a logarithmic relationship between the area of each lung slice and its mean density was derived (r = 0.9, n = 545, p less than 0.0001). The residual density, calculated as the difference between measured density and density predicted from the relationship with area, was shown to be normally distributed with a mean of 0 and a standard deviation of 25 Hounsfield units (chi 2 test: p less than 0.05). A presentation combining this residual density with the net plot is described. PMID- 3353884 TI - Diagnosis of pulmonary hypertension from radiographic estimates of pulmonary arterial size. AB - The reported accuracy of radiographic measurements in predicting pulmonary hypertension is very variable. Measurements of right and left descending pulmonary artery diameter have been reported to provide a correct diagnosis in as many as 98% of patients. A study was carried out to determine the predictive value of measurements made from the chest radiographs of 50 normal subjects and of 27 patients undergoing right heart catheterisation for cardiac or pulmonary vascular disease, taking account of radiographic magnification. After such corrections a right descending pulmonary artery diameter over 16.7 mm or a left descending pulmonary artery diameter of over 16.9 mm distinguished 12 of 23 pulmonary hypertensive subjects, with no false positive results. The diameter was then arbitrarily squared (any differences between patients and control subjects being exaggerated) and the product was divided by either predicted or actual lung volume in an attempt to correct for body size. The new index distinguished 19 of 23 patients with pulmonary hypertension, with one false positive, when the divisor was actual lung volume; when predicted lung volume was used 18 of 23 patients were distinguished, again with one false positive result. PMID- 3353886 TI - Value of Tru-cut lung biopsy in focal and diffuse lung disease. AB - The results of 382 consecutive Tru-cut lung biopsies were reviewed to evaluate this investigation. The age of the patients ranged from 16 to 84 years (median 63 years); 284 patients suffered from focal and 98 from diffuse lung disease. Of the 206 patients with focal disease in whom the final diagnosis was a malignancy, 161 (78%) had a correct biopsy diagnosis. Of the 78 patients in whom the final diagnosis was non-malignant disease, 60 (77%) had a correct biopsy diagnosis. In diffuse pulmonary disease the histological diagnosis was correct in 75 of 98 patients (77%). In focal benign disease and in diffuse disease the reliability of the diagnosis increased with the specificity of the diagnosis. Where the biopsy diagnosis was not in accordance with the final diagnosis, histological examination usually showed normal lung tissue (with or without non-specific inflammation), necrotic tissue, or no tissue at all. Two patients died from the procedure. Minor complications occurred in 18%. It is concluded that the usefulness of Tru-cut biopsy is not confined to malignant focal disease; it is also reliable in benign focal disease and diffuse pulmonary disease when a specific diagnosis is obtained. PMID- 3353885 TI - Lipoprotein macroaggregates in bronchoalveolar lavage fluid from patients with diffuse interstitial lung disease: comparison with idiopathic alveolar lipoproteinosis. AB - Lipoprotein macroaggregates were present in cytocentrifuge preparations of bronchoalveolar lavage fluid from four patients with diffuse lung diseases other than idiopathic alveolar lipoproteinosis. In three patients the primary diagnosis was cryptogenic fibrosing alveolitis and in one sarcoidosis. We confirmed the presence of large multilamellar aggregates of lipoprotein by ultrastructural examination in patients with both interstitial lung disease and idiopathic alveolar lipoproteinosis. The small lamellar bodies and amorphous debris found in idiopathic alveolar lipoproteinosis were rare in the patients with interstitial lung disease. The lavage fluid from patient with interstitial lung disease did not show the substantial alterations in phospholipid composition that were seen in lavage fluid in idiopathic alveolar lipoproteinosis. These ultrastructural and biochemical features may help to distinguish idiopathic from other causes of alveolar lipoproteinosis, particularly at an early stage, when differential diagnosis may be difficult. PMID- 3353887 TI - Fatal infection with Mycobacterium fortuitum associated with oesophageal achalasia. PMID- 3353889 TI - Bony metastases in desmoplastic pleural mesothelioma. PMID- 3353888 TI - Ciliary function in Young's syndrome. PMID- 3353890 TI - Splendore-Hoeppli phenomenon in bronchocentric granulomatosis. PMID- 3353891 TI - Effect of particle size of bronchodilator aerosols on lung distribution and pulmonary function in patients with chronic asthma. PMID- 3353892 TI - Low serum testosterone as an indicator of metastatic bronchial carcinoma. PMID- 3353893 TI - Effect of dietary supplementation with fish oil lipids on mild asthma. AB - Recruitment of inflammatory leucocytes to the airways may play a part in the pathogenesis of asthma. As dietary enrichment with fish oil lipids can suppress leucocyte function, the effect of these lipids on asthma control and neutrophil function was studied in 20 subjects with mild asthma. Twelve subjects received capsules containing 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid daily and eight subjects received placebo capsules containing olive oil for 10 weeks in a double blind fashion. Baseline specific airways conductance, airways responsiveness to histamine and exercise, diurnal peak expiratory flow, symptom scores, and bronchodilator use were measured. Neutrophil fatty acid composition was evaluated by gas chromatography, calcium ionophore induced neutrophil leukotriene (LT)B4 and LTB5 generation were measured by reverse phase high performance liquid chromatography and radioimmunoassay, and neutrophil chemotactic responses to formyl-methionyl-leucyl-phenylalanine (FMLP) and LTB4 were assessed by a microchemotaxis technique. Although the fish oil supplemented diet produced a greater than 10 fold increase in the eicosapentaenoic acid content of neutrophil phospholipids, there was no significant change in airways responsiveness to histamine or any change in any of the clinical measurements. After dietary supplementation with fish oil there was a 50% inhibition of total LTB (LTB4 + LTB5) generation by ionophore stimulated neutrophils and neutrophil chemotaxis was substantially suppressed. Neutrophil function remained unchanged in the placebo group. It is concluded that in subjects with mild asthma a fish oil enriched diet attenuates neutrophil function without changing the severity of asthma. PMID- 3353894 TI - Effects of a fish oil enriched diet on aspirin intolerant asthmatic patients: a pilot study. AB - The effect of a fish oil enriched diet containing about 3 g of eicosapentaenoic acid was studied in 10 patients with aspirin intolerant asthma. Subjects were studied during six weeks on a control diet followed by six weeks on the fish oil diet in a single blind study design. They were asked to record their peak expiratory flow (PEF) twice daily, bronchodilator and steroid doses, and subjective ratings of pulmonary symptoms on diary cards. There were no significant changes in symptom scores over the six weeks of either the control diet or the fish oil diet. PEF values, however, were significantly lower during the fifth and sixth week of the fish oil diet than during the control diet (308 v 262 l/min week 5 and 306 v 256 l/min week 6). Bronchodilator usage was also greater during the fifth and sixth week of the fish oil diet than during the control period (12.0 v 7.4 and 13.0 v 7.4 puffs a day in weeks 5 and 6). This pilot study suggests that fish diets may have a deleterious effect on patients with aspirin intolerant asthma. PMID- 3353896 TI - [In vitro fertilization]. PMID- 3353897 TI - [Hallux valgus. A retrospective evaluation of surgical results]. PMID- 3353895 TI - Effect of house dust mite avoidance measures on adult atopic asthma. AB - Twenty one adult patients with asthma, with positive skin test responses to the European house dust mite, Dermatophagoides pteronyssinus, were randomly allocated to a control group or to a group applying house dust mite avoidance measures. These included an initial application of liquid nitrogen to mattresses and bedroom carpets to kill the live house dust mite population. Histamine airway responsiveness, symptom scores, peak expiratory flow rates (PEF), and house dust mite numbers were determined during the two week pretrial and eight week trial periods. Nine patients in each group completed the study. By the end of the study there was a significant reduction in live mites in the "avoidance" group but not in the control group. The avoidance group showed a significant improvement in symptom scores measured on a linear analogue scale, in the number of hours each day spent wheezing (mean reduced from 8.6 to 4.5 hours), and in PEF (l/min) both in the morning (from 364 to 388) and in the evening (from 368 to 392). These changes were not found in the control group. The provocative concentration (PC) of histamine causing a 20% fall in FEV1 (PC20FEV1) had increased significantly in the avoidance group at eight weeks (from 0.58 to 2.3 mg/ml), whereas no change was seen in the control group (from 0.93 to 1.21 mg/ml). These results show that house dust mite avoidance, combined with initial killing of the mite by liquid nitrogen, diminishes airway responsiveness and improves asthma symptom control over an eight week period in adult asthmatic patients with house dust mite allergy. PMID- 3353898 TI - [Resurfacing arthroplasty of the hip joint]. PMID- 3353899 TI - [Normal pressure hydrocephalus. Critical evaluation and status]. PMID- 3353900 TI - [Legionnaires' disease]. PMID- 3353901 TI - [Human pentastomiasis]. PMID- 3353902 TI - [Biosynthesis of complement in mononuclear phagocytes]. PMID- 3353903 TI - [In vitro fertilization]. PMID- 3353904 TI - [The usefulness of simulation models in the understanding of the HIV epidemic]. PMID- 3353905 TI - [Urinary tract infections in women. Should intravenous urography be done in recurrent infections?]. PMID- 3353906 TI - [Ureteral obstruction following aortoiliac vascular surgery]. PMID- 3353907 TI - [Accidentally ligated ureter treated with percutaneous nephrostomy]. PMID- 3353908 TI - [Splenectomy. Indications and complications]. PMID- 3353910 TI - [Hydrocarbon pneumonitis in adults]. PMID- 3353909 TI - [The resistance of microorganisms in bacteremia]. PMID- 3353911 TI - [Inequalities in health habits in Norway in 1985]. PMID- 3353912 TI - [Contraception among women demanding abortion]. PMID- 3353913 TI - [Sterilization of women]. PMID- 3353914 TI - [Cerebral palsy in Vestfold 1970-1984. Occurrence in a period of decreasing perinatal and neonatal mortality]. PMID- 3353915 TI - [Ventricular rupture after mouth-to-mouth resuscitation without tube]. PMID- 3353916 TI - [Brain stem response audiometry in otoneurological diagnosis]. PMID- 3353917 TI - [Spinal epidural metastases]. PMID- 3353918 TI - [Polyorchidism]. PMID- 3353919 TI - [Tonsillar calcifications]. PMID- 3353920 TI - [Transfer of tissue by a microvascular technic]. PMID- 3353921 TI - [Psychiatry in general practice. Psychiatric problems and general practitioners in Telemark]. PMID- 3353922 TI - [Brief dynamic psychotherapy. A long-term follow-up study of 54 evaluated patients]. PMID- 3353924 TI - [Acute renal failure following surgery for abdominal aortic aneurysm]. PMID- 3353923 TI - [Immediate allergic reactions to natural rubber]. PMID- 3353925 TI - [Treatment of liver injuries]. PMID- 3353926 TI - [Secondary lens implantation]. PMID- 3353927 TI - [Where ought psychiatric patients be placed? A survey of ideal and realistic residential and therapeutic possibilities for patients in psychiatric hospitals]. PMID- 3353928 TI - [Mass screening of women. Experiences in a small municipality]. PMID- 3353930 TI - [Treatment of hypertension and prevention of coronary heart disease]. PMID- 3353929 TI - [AIDS and statistics]. PMID- 3353931 TI - [Shock wave therapy of urolithiasis. Norwegian experiences]. PMID- 3353932 TI - [Recurrent kidney calculi. Metabolic examination and medical prevention]. PMID- 3353933 TI - [Rhabdomyolysis and acute kidney failure]. PMID- 3353934 TI - [Pulmonary aluminosis in an aluminum worker]. PMID- 3353935 TI - [Atypical pulmonary mycobacteriosis. Occurrence, manifestations and treatment in Hordaland, Sogn and Fjordane]. PMID- 3353936 TI - [Atypical Mycobacterium infections of the neck]. PMID- 3353937 TI - [Mesenteric cyst. Mesenteric cyst as the cause of an abdominal tumor]. PMID- 3353938 TI - [Aspergillosis of the maxillary sinus]. PMID- 3353939 TI - [Possible decrease in semen quality over a 20-year period]. PMID- 3353940 TI - [Pediatric aspects of in vitro fertilization]. PMID- 3353941 TI - [A disaster in a local community. Experiences following an airplane crash in Spitsbergen]. PMID- 3353942 TI - [AIDS testing on a large scale is needed in the fight against the epidemic]. PMID- 3353943 TI - [Female sexual problems after proctectomy]. PMID- 3353944 TI - [Sexual abuse of children. Manifestations and management in primary health care]. PMID- 3353945 TI - [Thoracic empyema]. PMID- 3353947 TI - [Brachial plexus injuries in the newborn infant]. PMID- 3353946 TI - [Lung abscess]. PMID- 3353948 TI - [Septic cavernous sinus thrombosis]. PMID- 3353949 TI - [Trichomonas vaginalis infection. Frequency and diagnosis in women]. PMID- 3353950 TI - [Pharmacological induction of leukemia cell differentiation]. PMID- 3353951 TI - [Late femur shaft fractures around an implanted hip prosthesis]. PMID- 3353952 TI - [Drug abuse among prisoners. A questionnaire study of 4 Norwegian prisons]. PMID- 3353953 TI - [Fish and fish oils in the diet. Can increased use minimize the occurrence of coronary heart disease?]. PMID- 3353954 TI - [Sex behavior--attitude and practice for teenagers]. PMID- 3353955 TI - [Sex education among teenagers--is it effective?]. PMID- 3353957 TI - [Chronic subdural hematoma. Surgical or conservative treatment?]. PMID- 3353956 TI - [Self poisoning. Medical and social aspects]. PMID- 3353958 TI - [Fractures of the neck of the talus]. PMID- 3353959 TI - [Erectile impotence]. PMID- 3353960 TI - [Impotence and arterial circulatory disorders]. PMID- 3353961 TI - [Penile blood pressure measurements]. PMID- 3353962 TI - [Autologous blood transfusion. More common in the near future?]. PMID- 3353963 TI - [Female general practitioners--female patients]. PMID- 3353964 TI - [Outcome of the HIV epidemic in Norway. Results of an HIV antibody survey at the Microbiological Laboratory, Ulleval Hospital 1986-1987]. PMID- 3353965 TI - [Drug handling in homes for the aged. Suggestion for routines based on the principle of patient-related drugs]. PMID- 3353966 TI - [An evaluation of routines for drug handling in homes for the aged]. PMID- 3353967 TI - [The paranoiac--the enfant terrible of psychiatry]. PMID- 3353968 TI - [Diabetic neuropathy]. PMID- 3353970 TI - [Photochemotherapy and skin cancer. The occurrence of premalignant and malignant skin changes in patients with psoriasis treated with photochemotherapy (PUVA therapy)]. PMID- 3353969 TI - [Digital rectal exploration as a screening for prostatic cancer]. PMID- 3353971 TI - [Erectile impotence and disorders of venous circulation]. PMID- 3353972 TI - [Cavernosography in erectile dysfunction]. PMID- 3353973 TI - [Congenital curvature of the erect penis without simultaneous changes in the urethra or corpus spongiosum and with normal erection]. PMID- 3353974 TI - [Constrictive pericarditis. Diagnosis by echocardiography]. PMID- 3353975 TI - [Unemployment and health]. PMID- 3353977 TI - Batting 1,000 in medical staff marketing: strategies for marketplace achievement in turbulent times. PMID- 3353976 TI - Making the mental shift: strategies for superior hospital management. PMID- 3353978 TI - Maximizing the potential of marketing personnel. PMID- 3353979 TI - What is excellence in health care marketing? PMID- 3353981 TI - Networking strategies for hospitals. PMID- 3353980 TI - Strategic market planning. PMID- 3353982 TI - Product-line management: concept to reality. PMID- 3353983 TI - Marketing for success through product-line development. PMID- 3353986 TI - Pharmacokinetics of clearance in the maternal-fetal amniotic fluid system of the rat. AB - A pharmacokinetic model of the maternal-fetal amniotic fluid system was designed to permit calculation of clearances from the steady-state concentrations of p phenylbenzoic acid (PPBA) during infusion of PPBA into the maternal vein and the amniotic fluid of pregnant rats on the 16th to the 21st day of gestation. Transplacental clearance from the fetus to the mother maintained fairly constant values until the 19th day of gestation but decreased on Days 20 and 21 of gestation. Both clearances from the fetus into the amniotic fluid and from the amniotic fluid into the fetus showed higher values during the earlier stages of gestation, indicating that amniotic fluid may play an important role in the pharmacokinetics of PPBA in the fetus during the earlier stage of gestation. Fetal tissue clearance appeared to contribute to the elimination of PPBA in the fetus on Days 20 and 21 of gestation. Transplacental clearance from the mother to the fetus and clearance by nonplacental elimination in the mother increased with the day of gestation. The relationship between developmental changes in clearances and physiological changes in placenta and fetal tissues is discussed. The present model provides a basis for calculation of clearances in the maternal fetal amniotic fluid system. PMID- 3353985 TI - Mirex uptake and tissue disposition in intact and adrenalectomized rats. AB - The toxicity of mirex, an organochlorine insecticide, is increased significantly in adrenalectomized rats. To determine if this might be due to alterations in the tissue distribution of mirex, a disposition study was conducted in intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats. The peak plasma levels of [14C]mirex were shifted from 2 hr in intact and adrenalectomized corticosterone-supplemented rats to 4 hr in the adrenalectomized rats. The initial uptake and disposition of [14C]mirex in the brain of the intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats was essentially the same from 0.5 to 6 hr after dosing. By 48 hr after dosing, the [14C]mirex concentration in the brain of intact and adrenalectomized rats was significantly higher than that in adrenalectomized corticosterone-supplemented rats. Brain to plasma ratios reflected this difference. Corticosterone supplements to adrenalectomized rats decreased the absorption of [14C]mirex in the brain. The uptake of [14C]mirex during the initial 6 hr after dosing in all other tissues studied (liver, kidney, testes, and omental fat) was essentially the same for the three treatment groups. By 48 hr postdose, [14C]mirex concentration per liver was significantly higher in intact than in adrenalectomized and adrenalectomized corticosterone-supplemented rats. The difference in [14C]mirex disposition between the three treatment groups was not due to alterations in metabolism or elimination. PMID- 3353984 TI - Effects of N,N,N',N'-ethylenediaminetetramethylene phosphonic acid on cortical bone remodeling in the adult dog. AB - Phosphonic acids are of interest because of their potential usefulness in the treatment of disorders of bone and mineral metabolism, as a treatment for dental calculus, and as skeletal imaging agents. The effects of oral doses of N,N,N',N' ethylenediaminetetramethylene phosphonic acid (EDITEMPA) on cortical bone remodeling and histology of adult dogs were determined. After treatment for 3 and 6 months, there were dose-related changes observed in cortical bone as measured using histomorphometric methods. With higher doses, EDITEMPA treatment resulted in the accumulation of osteoid due to impaired or delayed mineralization of bone. There was an increased mineralized and osseous tissue porosity suggesting an early increase in bone resorption perhaps due to an increased activation of bone remodeling. PMID- 3353987 TI - Trifluoroethanol and its oxidative metabolites: comparison of in vivo and in vitro effects in rat testis. AB - Trifluoroethanol (TFE) and trifluoroacetaldehyde (TFALD) produced a reduction in testis weight 3 days after a single oral dose of 10 mg/kg. In contrast, administration of trifluoroacetic acid (TFAA) caused no observable testicular effects. Reduction in testis weight was accompanied by morphological changes, involving specific damage to pachytene and dividing spermatocytes, and round spermatids. In an in vitro Sertoli/germ cell co-culture system, only TFALD was found to produce dose-related effects at concentrations of 10(-3) and 10(-4) M. There was increased germ cell loss from the cultures, particularly loss of pachytene and dividing spermatocytes, accompanied by leakage of the pachytene spermatocyte marker enzyme, lactate dehydrogenase-X. TFE and TFAA did not produce these effects in the culture system at concentrations equimolar with TFALD. These results suggest that TFALD may play a critical role in the development of the testis lesion seen with TFE in vivo. The effects seen both in vivo and in vitro were remarkably similar to those previously reported for another substituted alcohol and its metabolites, ethylene glycol monomethyl ether. It is postulated that the two series of compounds may have a similar mode of action on rat testis. PMID- 3353988 TI - Methyl isobutyl ketone metabolites and potentiation of the cholestasis induced in rats by a manganese-bilirubin combination or manganese alone. AB - Methyl isobutyl ketone (MIBK) has recently been shown to potentiate the cholestasis induced by manganese-bilirubin (Mn-BR) or manganese (Mn) in rats. In this study, we investigated the effect of 4-methyl-2-pentanol (4MPOL) and 4 hydroxymethyl isobutyl ketone (4-OHMIBK), two major metabolites of MIBK, on these models of cholestasis. Dosages varying from 1.88 to 15 mmol/kg 4MPOL or 4-OHMIBK were administered once, 18 hr prior to the administration of a cholestatic Mn-BR combination. The cholestatic effect of the manganese-bilirubin combination was enhanced with dosages of 4MPOL of 3.75 mmol/kg and larger. On the other hand, dosages smaller than 15 mmol/kg of 4-OHMIBK did not potentiate the Mn-BR cholestasis. Daily pretreatment for 3 days resulted in an increased response to the cholestatic challenges of either Mn-BR or Mn alone. 4MPOL administered repetitively was a better potentiator than 4-OHMIBK with the Mn-BR model of cholestasis. However, with Mn alone, 4-OHMIBK proved to be more effective. 4MPOL and 4-OHMIBK per se were devoid of cholestatic properties, since the bile flow measured prior to the cholestatic challenge was not decreased and in some cases was significantly greater than that of vehicle-pretreated animals. These results show that MIBK metabolites can potentiate the cholestatic form of hepatotoxicity. PMID- 3353989 TI - Convulsant properties of cyclotrimethylenetrinitramine (RDX): spontaneous audiogenic, and amygdaloid kindled seizure activity. AB - Dose-effect and time course relationships were determined for the effects of the explosive cyclotrimethylenetrinitramine (RDX) on seizure susceptibility. Male Long Evans rats treated with 0-60 mg/kg RDX po were monitored for spontaneous seizures during an 8-hr interval between dosing and audiogenic (AG) seizure testing. Blood samples for analyzing plasma RDX concentrations were obtained immediately thereafter. Spontaneous and AG seizures were observed at dosages as low as 10-12.5 mg/kg, with significant seizure incidence induced by dosages of 25.0 mg/kg (5.34 micrograms RDX/ml plasma) and 50.0 mg/kg (8.28 micrograms RDX/ml plasma), respectively. Spontaneous seizure incidence peaked at 2 hr for all RDX treatment groups, then decreased (12.5 and 25.0 mg/kg) or remained elevated (50.0 mg/kg) for the remaining 6 hr. In contrast, AG seizures (37.5 mg/kg) could be elicited only at 8 and 16 hr, despite significant elevation of plasma RDX concentrations at 2 and 4 hr. Because limbic system involvement was suggested by spontaneous seizure characteristics, the rate of amygdaloid kindling was measured following daily treatment with 6.0 mg/kg. This dosage significantly accelerated kindling development without inducing spontaneous seizures or producing an accumulation of RDX in plasma. These data provide preliminary evidence that limbic structures may participate in RDX-induced seizure susceptibility. PMID- 3353990 TI - Effects of chronic exposure to ozone on collagen in rat lung. AB - Pulmonary fibrosis is a consequence of severe injury from some toxic agents including high doses of ozone. It is not known, however, whether chronic exposure to low doses of ozone, such as those encountered in polluted ambient atmospheres, could also result in abnormal accumulations of lung collagen. Rats were exposed to ozone for 20 hr per day, 7 days per week for 3, 6, 12, and 18 months at concentrations of 0.12, 0.25, or 0.50 ppm. Controls were exposed under identical conditions to purified air. Upon removal from the chambers, rats were euthanized and lung tissue slices incubated with [14C]proline. The incorporation of 14C into hydroxyproline and the total hydroxyproline content of lung tissue were measured as estimates of lung collagen synthesis and content, respectively. The formation of labeled hydroxyproline tended to decrease significantly with time in controls and at the three ozone doses. There were, however, no significant dose-related changes at any of the time points tested. Total lung hydroxyproline increased with age in all groups, but no dose-related changes were detected at any time point. It was concluded that chronic exposure of rats to ozone at concentrations which approximate ambient urban concentrations did not affect normal age-related changes in either synthesis or accumulation of lung collagen. PMID- 3353991 TI - The effects of mono-(2-ethylhexyl)-phthalate on rat Sertoli cell-enriched primary cultures. AB - There is considerable evidence from in vivo studies that the Sertoli cell is an initial target cell for the actions of phthalates in the rodent testis. Because this metabolically active cell type plays a central role in spermatogenesis, we examined the effects of a toxic phthalate, mono-(2-ethylhexyl)-phthalate (MEHP), on the secretory and synthetic activities of primary testicular cell cultures isolated from 18-day-old rats. These cultures were 78-84% Sertoli cells. Exposure to MEHP decreased cellular ATP by ca. 20%, decreased production of radiolabeled 14CO2 from acetate, and decreased media levels of pyruvate, while it increased media levels of lactate and intracellular lipid. Protein synthesis, evaluated by radiolabeled leucine incorporation, was not affected by MEHP. Mitochondrial succinate dehydrogenase activity was decreased in the presence of MEHP. Michaelis Menton kinetic analysis indicated this was a mixed inhibition. There was no apparent change in mitochondrial Rhodamine 123 uptake. These data are consistent with the concept that mitochondria are one target for the actions of MEHP in the Sertoli cell. PMID- 3353992 TI - Reproduction studies in rats treated with ornidazole. AB - Reproduction studies were performed with ornidazole, a compound with trichomonacidal activity. Male rats were treated for 61 days prior to mating and female rats were treated for 2 weeks prior to mating and throughout gestation and lactation at doses of 0 (control), 25, 100, and 400 mg of ornidazole/kg/day. A decrease in the pregnancy rate was observed in high-dose rats without altered mating performance. Crossover matings between high-dose treated and control male and female rats showed that male but not female fertility was affected and that the effect on fertility was reversible within several days after the cessation of treatment. Testicular and epididymal weights were not altered in treated male rats. Histopathological examination revealed that spermatogenesis and the testes were normal and that the epididymides of treated male rats contained normal appearing sperm. It is concluded that ornidazole, at high dosages, produces infertility in the male rat; however, unlike many other 5-nitroimidazole compounds which are reported to inhibit spermatogenesis, no effect on spermatogenesis was observed under the conditions of these studies. This in conjunction with the rapid reversibility of infertility suggests that the mode of action of ornidazole involves a rapidly reversible effect on epididymal sperm function. PMID- 3353993 TI - The effect of ornidazole on fertility and epididymal sperm function in rats. AB - A comprehensive study of male fertility and sperm production and function was performed in 20 control and 20 rats treated with ornidazole, a compound with trichomonacidal activity. Rats were treated for 4 weeks at dosages of 0 (control) and 400 mg/kg/day of ornidazole during which fertility was assessed by weekly matings. Testicular sperm production and epididymal sperm function were assessed in one-half of the rats while the reversibility of effects after a 2-week recovery period was assessed in the remaining half. Male rats treated with ornidazole were infertile during the second week of treatment. After 4 weeks of treatment, testicular and epididymal weights, testicular spermatid counts, epididymal sperm reserves, sperm morphology, and sperm viability were similar in treated and control rats. A quantitative assessment of epididymal sperm motility using a dark-field photomicroscope with a stroboscopic light source revealed that ornidazole markedly inhibited sperm motility. Although the percentage of nonmotile sperm was not substantially increased in treated rats, the vigor of tail movement was markedly decreased which resulted in decreased sperm velocity. Restoration of fertility and normal sperm motility and velocity were observed in the group of recovery rats assessed 2 weeks after the cessation of ornidazole treatment. It is concluded that ornidazole, at a high dosage of 400 mg/kg/day, produces infertility in male rats by inhibiting epididymal sperm motility in terms of decreased sperm velocity. These effects are rapidly reversible after the cessation of treatment. PMID- 3353994 TI - Specific alteration of the form of selenium in fetal liver on maternal methylmercury treatment. AB - We have recently reported that maternal administration of methylmercury caused a striking increase in the selenium concentration in fetal liver accompanied by a decrease in selenium-dependent glutathione peroxidase (GSH-Px) activity. These changes resulted in the lowered bioavailability of selenium as far as the GSH-Px activity was concerned. The present study demonstrated that maternal administration of methylmercury caused a specific alteration of the form of selenium in fetal liver. Sephadex G-200 gel filtration of liver cytosols revealed an additional major peak of selenium in the fetal livers of mice treated with methylmercury. This peak was not present in the liver, kidney, or placenta of mothers treated with methylmercury. PMID- 3353995 TI - Effect of dietary vitamin E on ferric nitrilotriacetate-induced nephrotoxicity in rats. AB - The effect of dietary vitamin E on renal tissue damage and lipid peroxidation was investigated following treatment with ferric nitrilotriacetate (Fe-NTA) in rats. Almost 100% renal proximal tubular necrosis was observed in the vitamin E deficient rats following Fe-NTA treatment (5 mgFe/kg body wt, ip) as early as 12 hr. In the vitamin E-supplemented rats, no injury was observed in the proximal convoluted (cortical) tubules, although some injury was seen in the medullary outer stripe (mostly pars recta of the proximal tubules) 24 hr after Fe-NTA treatment. The tissue lipid peroxidation was dose-dependently increased 1 hr after a single ip injection of Fe-NTA (1 to 10 mg Fe/kg body wt). Vitamin E deficient animals had an increased tissue content of thiobarbituric acid-reactive substance following Fe-NTA treatment, whereas vitamin E-supplemented animals showed suppressed lipid peroxidation. This study indicates that vitamin E provides some protection against the nephrotoxicity and associated lipid peroxidation induced by Fe-NTA. PMID- 3353996 TI - Macromolecular interactions of inhaled methylene chloride in rats and mice. AB - The in vivo interaction of methylene chloride and its metabolites with F344 rat and B6C3F1 mouse lung and liver DNA was measured after inhalation exposure to 4000 ppm [14C]methylene chloride for 3 hr. DNA was isolated from the tissues 6, 12, and 24 hr after the start of exposure and analyzed for total radioactivity and the distribution of radioactivity within enzymatically hydrolyzed DNA samples. Covalent binding to hepatic protein was also measured. A further group of rats and mice were dosed intravenously with [14C]formate after exposure to nonradiolabeled methylene chloride for 3 hr to determine the pattern of labeling resulting from incorporation of formate into DNA via the C-1 pool. Low levels of radioactivity were found in DNA from lungs and livers of both rats and mice exposed to [14C]methylene chloride. Two- to fourfold higher levels were found in mouse DNA and protein than in rat. Chromatographic analysis of the DNA nucleosides showed the radioactivity to be associated with the normal constituents of DNA. No peaks of radioactivity were found that did not coincide with peaks of radioactivity present in hydrolyzed DNA from formate-treated rats and mice. Under the conditions of this study there was no evidence for alkylation of DNA by methylene chloride in either rats or mice. PMID- 3353997 TI - Pharmacokinetics of tetrachloroethylene. AB - A physiological pharmacokinetic model is developed to describe the pharmacokinetics of tetrachloroethylene (PCE) in mice, rats, and humans. The body is divided into four tissue compartments (vessel-rich, muscle, slowly perfused fat, and liver) connected by the arterial and venous blood flow pathways. The physiological parameters of the model are blood flow rates, cardiac output, tissue volumes, ventilation rate, and tissue/air and blood/air partition coefficients. Metabolism is assumed to occur only in the liver compartment and is described by a combination of a linear metabolic component and a Michaelis-Menten component. The metabolic parameters for PCE were determined by fitting model predictions to species-specific empirical data. Comparison of model results with independent empirical data on inhalation and gavage exposures in mice, rats, and humans demonstrates that the physiological pharmacokinetic model can be used to determine the time course of PCE in these species. We show that human metabolic parameters can be predicted by scaling rat metabolic parameters as a function of body weight, whereas scaling of the metabolic parameters of mice overestimates human metabolism. PMID- 3353998 TI - Hydronephrosis in rats associated with postnatal exposure to a fatty acid oxidation inhibitor. AB - Methyl palmoxirate, an inhibitor of long-chain fatty acid oxidation, was administered by gavage (0, 1, 5, or 20 mg/kg/day) to female rats over the last third of gestation and throughout lactation. Weight gain (mid- and high-dosage group) and survivability (high-dosage group) were significantly (p less than or equal to 0.05) reduced in offspring of methyl palmoxirate-treated dams as compared to control offspring. Mid- and high-dosage male offspring found dead after Day 4 of lactation exhibited grossly distended bladders and renal pelves. A dosage-related increased incidence of dilated renal pelves was observed in both sexes at necropsy of 21-day-old mid- and high-dosage group pups. Microscopic examination of the urinary tracts of a number of affected pups revealed renal parenchymal atrophy and urethral obstruction. Drug disposition studies indicated lactating pups were exposed to significant amounts of methyl palmoxirate via mammary secretions. Cross-fostering experimentation suggested that some of the adverse effects observed in offspring were due to lactational, rather than in utero, exposure. PMID- 3353999 TI - Disposition of octachlorodibenzo-p-dioxin (OCDD) in male rats. AB - Octachlorodibenzo-p-dioxin (OCDD) is a widespread environmental contaminant which has been reported to be nontoxic after acute administration. The disposition of [14C]OCDD was studied in male Fischer 344 rats in order to better assess the significance of chronic environmental exposure to OCDD. Rats were treated with 50 micrograms OCDD/kg iv, and 50, 500, or 5000 micrograms/kg po and held in individual metabolism cages for 3 days. Additional rats treated iv were held up to 56 days to follow elimination of OCDD-derived radioactivity and to determine terminal tissue distribution. Feces was the major route of elimination after both routes of exposure with little radioactivity ever appearing in the urine. Gastrointestinal absorption was nonlinear between 500 and 5000 micrograms/kg, never exceeding 10% of the administered dose. Liver was the major depot, followed by adipose tissue and skin. No metabolites of OCDD were detected in tissues, bile, or excreta. The whole-body half-life for the elimination of OCDD was between 3 and 5 months. Repeated oral exposure resulted in linear accumulation of OCDD in the tissues. Thus, OCDD, while poorly absorbed, can accumulate upon low dose, repeated exposure and concentrate in the liver and adipose tissue. PMID- 3354000 TI - Dioxin-like effects observed in male rats following exposure to octachlorodibenzo p-dioxin (OCDD) during a 13-week study. AB - Octachlorodibenzo-p-dioxin (OCDD) is a ubiquitous environmental pollutant which has been reported to be nontoxic following acute exposure but has recently been shown to accumulate upon repeated exposure. To determine if this accumulation results in toxic effects, male Fischer 344 rats were treated with 50 micrograms/kg [14C]OCDD by gavage for 10, 20, 40, or 65 times (once a day, 5 days/week) and terminated 3 days postexposure. OCDD accumulated linearly with increasing number of doses and the liver was the major depot, while the adipose served as a secondary sink. Hepatic accumulation resulted in alteration of several biochemical parameters. In animals given 65 doses of OCDD, 7 ethoxyresorufin-O-deethylase activity was elevated 40-fold over controls. Total cytochrome P-450 content doubled and exhibited a 2-nm blue-shift in the Soret maximum for the CO-reduced complex. Treatment-related cytoplasmic fatty vacuolization in the liver was observed concomitant with the biochemical alterations. Thus, subchronic exposure to OCDD appears to cause effects similar to those observed following exposure to low levels of TCDD, but is only 1/100 1/1000 as potent. Such a potency, given the persistent environmental levels to which man may be exposed during a lifetime, suggests that OCDD may pose a potential risk to human health. PMID- 3354001 TI - Strain dependence in mice of resistance and susceptibility to the testicular effects of cadmium: assessment of the role of testicular cadmium-binding proteins. AB - The nature of the cadmium (Cd)-binding proteins in the mouse testes is unknown, although some studies have implied metallothionein (MT) is responsible for the marked strain dependence of Cd-induced testicular necrosis in mice. This study attempted to define the role of MT in strain-dependent Cd resistance using NFS (susceptible) and BALB/c (resistant) mice. In all cases, testicular proteins were compared to hepatic MT isolated after treatment with zinc (Zn). A low-molecular weight (Mr) Zn-, Cd-binding protein was detected in testicular and hepatic cytosol from both strains after gel filtration. These proteins were extractable by heat treatment and sequential acetone precipitation. When such extracts were further purified with reverse-phase HPLC, two forms of authentic MT were shown by amino acid analysis from both NFS and BALB/c livers. However, of two testicular forms separated by HPLC from NFS and BALB/c mice, neither could be classified as MT based on amino acid composition. Methylation of the MT-I gene was also studied in testicular and hepatic DNAs isolated from control mice or from mice made resistant to Cd-induced testicular necrosis by Zn treatment. Major differences in methylation between tissues were seen, as the testicular gene of both NFS and BALB/c mice was highly methylated, a condition often linked to genetic quiescence. Zn treatment had no effect on MT-I gene methylation in testes of either strain, although rendering the NFS strain resistant to Cd. Zn treatment did not alter levels of this testicular protein in either strain while causing a marked induction of hepatic MT in both. These results indicate the low-Mr Cd-, Zn binding proteins present in the testes of both resistant and susceptible mice are not MTs and further that the MT gene may not be expressed in either strain. PMID- 3354003 TI - Teratogenic effects of benzo[a]pyrene in developing chick embryo. AB - The effect of benzo[a]pyrene (BP), an established carcinogen, on developing chick embryos was investigated. The embryos were exposed in different stages of development to various doses of BP via the yolk sac route. This resulted in retarded growth, as reflected by lower embryonic body weight, reduced crown-rump length and bill length. Abnormal survivors showed remarkably twisted legs with shortening of the bones, abdominal oedema, haematomas, blisters and a short neck. These findings suggest that BP is a teratogen when injected via this route, and the 'oedema syndrome' is a possible mechanism causing teratogenic effects in developing chick embryos when treated with BP. PMID- 3354002 TI - Induction of hepatic peroxisome proliferation in mice by lactofen, a diphenyl ether herbicide. AB - A technical grade of lactofen (1'[carboethoxy]ethyl 5-[2-chloro-4-[trifluoro methyl] phenoxy]-2-nitrobenzoate) has been shown to induce liver tumors in mice. To determine a possible mechanism of action, the effect of exposure for 7 weeks to dietary concentrations of 2, 10, 50, and 250 ppm technical grade lactofen and 250 ppm of pure lactofen was studied for various liver parameters in groups of male and female CD-1 mice. Liver-weight to body-weight ratio, liver catalase, liver acyl-CoA oxidase, liver cell cytoplasmic eosinophilia, nuclear and cellular size, and peroxisomal staining were increased by the tumorigenic dose of lactofen, i.e., 250 ppm, in a fashion similar to the comparison chemical nafenopin (500 ppm), which is a peroxisome proliferator. Lower doses of lactofen that were reported as nontumorigenic had little or no effect on these parameters. Thus, pure and technical grade lactofen appear to induce murine liver tumors through a mechanism similar to epigenetic hepatocarcinogens of the peroxisome proliferating type. PMID- 3354004 TI - Effect of androgens on phalloidin-induced liver toxicity in mice. AB - A single i.p. dose of phalloidin, 0.75 or 1 mg/kg body weight, induced peliosis hepatis-like lesion (PHLL) at 3 h after injection to mice. Pretreatment with various doses of testosterone propionate for 7 days enhanced phalloidin-induced PHLL. Other anabolic steroids, methyltestosterone, methandriol. fluoxymesterone and oxymetholone had no effect. PMID- 3354005 TI - Effect of di(2-ethylhexyl)phthalate (DEHP) on hepatic mixed function oxidases in different animal species. AB - Administration of 2000 mg/kg of di(2-ethylhexyl)phthalate (DEHP) for a period of 7 or 15 days in rats, mice, guinea pigs and rabbits produced a differential effect as judged by alterations in body weight gain, liver weight and activities of mixed function oxidases. DEHP exposure for 7 days caused an increase in the activity of aniline hydroxylase, arylhydrocarbon hydroxylase and ethylmorphine N demethylase in rats, mice and guinea pigs, but a decrease in that of rabbits. However, exposure for 15 days produced a smaller degree of increase in the activity of these enzymes in rats and mice and even produced a decrease in the activity of these enzymes in guinea pigs. This differential response of DEHP in various animal species suggests a species difference in the toxicity of the plasticizer. PMID- 3354006 TI - Metabolism of chloral hydrate in the anoxic perfused liver. AB - The metabolism of chloral hydrate (CH) under anoxic conditions was investigated in the non-recirculating, hemoglobin-free liver perfusion system. CH uptake in the anoxic liver decreased to about 80% of that in the oxygen-supplied liver. The reduction of CH to trichloroethanol (TCE) increased and the oxidation of CH to trichloroacetic acid (TCA) decreased. The TCE/TCA ratio increased; however, the total trichloro compounds, that is TCE and TCA, were not significantly altered by anoxia. Though approximate 14% of the CH infused into the oxygen-supplied liver was changed to substances other than TCE or TCA, the unknown part was a very small portion in the anoxic liver. The decrease in CH uptake, by the anoxic liver, is thought to be equivalent to the decrease of the unknown metabolites. The TCE/TCA ratio under anoxia was also altered by pyruvate or lactate infusion. PMID- 3354008 TI - Comparison of the trichothecenes deoxynivalenol and T-2 toxin for their effects on brain biogenic monoamines in the rat. AB - Male Sprague-Dawley rats (180 g) were orally dosed with deoxynivalenol (DON) and T-2 toxin at 2.5 mg kg-1 body weight. Brains were collected 24 h postdosing, dissected into five brain regions and analyzed for biogenic monoamines by high performance liquid chromatography with electrochemical detection. DON and T-2 toxin treatment resulted in significantly elevated concentrations of the indoleamines, serotonin (HT) and 5-hydroxy-3-indoleacetic acid (HIAA) in all brain regions examined, whereas norepinephrine (NE) and dopamine (DA) regional concentrations were not significantly altered. These results indicate that DON and T-2 toxin influence brain biogenic monamine metabolism, and suggest that the central nervous system (CNS) actions of these trichothecenes are similar. PMID- 3354007 TI - In vitro penetration of pesticides through human newborn foreskin. AB - The in vitro dermal penetration of 14C-labelled parathion, fenvalerate, carbofuran, and lindane through fresh full-thickness human newborn foreskin was determined at 1, 6, 24, and 48 h. The pesticides were applied to a constant dosing area (0.031 cm2), and a fixed dose (1.18 microgram), for each of the compounds studied. 90%, or greater, of the labelled pesticides were recovered in all cases. Carbofuran showed the greatest mean penetration of 82% followed by parathion and lindane with mean penetrations of 79 and 66%, respectively. Fenvalerate exhibited a mean penetration of 9% which is significantly lower than that of the other three compounds. No difference was noted in the penetration of pesticides through human skin from blacks and whites. PMID- 3354009 TI - Effects of culture conditions on susceptibility of alveolar epithelial cell monolayers to NO2. AB - The effects of nitrogen dioxide (NO2) exposure on primary cultured monolayers of rat type II pneumocytes were investigated as a function of the isolation and culture conditions. Monolayers were cultured in Eagle's minimum essential medium (MEM) and in MEM supplemented with Ham's F-12; in some experiments, the initial cell suspension was also replated after 3 h. Both supplementation of the basal medium and replating increased the sensitivity of the monolayers to NO2, as measured by reduction in dome formation of plastic dishes 24 h post-exposure. These findings suggest that comparisons of in vitro toxicologic observations may be complicated by the effects of specific experimental conditions. PMID- 3354010 TI - The mutagenicity of urine fractions from patients administered antineoplastic therapy. AB - A concern among hospital personnel is their exposure to mutagenic drugs and in the incidental exposures that could occur in caring for the patients. In a recent published study the mutagenicity of urine from patients administered antineoplastic drugs was determined and techniques were developed to chemically inactivate the mutagenicity. A question still remained as to what components of the excreted urine were mutagenic. Urine samples from patients receiving mutagenic drugs were fractionated by high pressure liquid chromatography (HPLC) to then assay by the Ames test the collected and concentrated fractions to determine what were the mutagenic compounds in the urine. Urine samples from patients on single agent cancer treatment with cisplatin, cyclophosphamide, doxorubicin and mitomycin C were assayed. In general, all urine samples containing the cytotoxic agents studied were mutagenic because of the presence of the parent compound, except cyclophosphamide which requires activation and therefore an active metabolite was the major mutagenic constituent in the urine sample. This data indicates that the mutagenicity of urine from patients receiving these antineoplastic agents is the result of the parent compound or a single major metabolite. PMID- 3354011 TI - Effect of T-2 toxin on lipid peroxidation in rats: elevation of conjugated diene formation. AB - A single dose of T-2 toxin (3.6 mg/kg, oral) enhanced conjugated diene formation in rat liver, spleen, kidney, thymus and bone marrow, implying that lipid peroxidation was stimulated. Lipid peroxidation showed apparent specificity in each organ as time elapsed (1-6 h). In liver and kidney maximum stimulation (+74% and +72%, respectively) was noted at 1 h after T-2 treatment. In spleen and thymus, maximum values were observed at 3 h (+95% and +32%, respectively). In bone marrow, a continuous elevation was noted which reached a maximum at 6 h (+112%). Results obtained from serum transaminase assay and histological examination suggested that T-2 toxin exhibited low hepatotoxicity even when the rat received a dose close to the oral LD50. PMID- 3354012 TI - Early diagnosis of basilar artery occlusion using magnetic resonance imaging. AB - Three patients with a clinical diagnosis of pontine infarction probably due to basilar artery occlusion were studied with magnetic resonance imaging within 24 hours after onset or latest progression of symptoms. The earliest changes on magnetic resonance images were an absence of signal void in the basilar artery suggestive of severe reduction of blood flow or occlusion (flow-void phenomena). The presumed basilar artery thrombosis was best demonstrated as a linear structure isointense or hyperintense with the brainstem in the pontine cistern on T1-weighted parasagittal images and as either absence of flow-void phenomena or higher signal intensity at various levels corresponding to the course of the basilar artery on the axial T2-weighted images. Brainstem parenchymal changes characteristic of infarction were not obvious for at least 12 hours after onset or 90 minutes after latest progression of symptoms and were best shown by both axial and coronal T2-weighted images. Recognition of these magnetic resonance imaging findings may allow earlier diagnosis and treatment of acute ischemia in the vertebrobasilar system. PMID- 3354014 TI - Treatment of systemic hypertension and intracranial hypertension in cases of brain hemorrhage. AB - We studied the effects of nifedipine, chlorpromazine, reserpine, furosemide, and thiopental on the mean arterial blood pressure, mean intracranial pressure, and cerebral perfusion pressure in 38 patients with increased intracranial pressure resulting from either hemorrhagic cerebrovascular disease or systemic hypertension. These agents are widely used in neurosurgical practice for the treatment of systemic hypertension. Patients were assigned to two groups on the basis of their mean intracranial pressure. Group I comprised 20 patients with a mean intracranial pressure of 20-40 mm Hg (moderately increased ICP group), and Group II consisted of 18 patients with a mean intracranial pressure of greater than 40 mm Hg (severely increased ICP group). Nifedipine, chlorpromazine, and reserpine reduced mean arterial blood pressure by 18-20% in both groups (p less than 0.05 in each). In Group I these agents raised mean intracranial pressure by 10-35% and decreased cerebral perfusion pressure by 20-32% (p less than 0.05 for both), but in Group II these changes were more marked: mean intracranial pressure increased 38-64% and cerebral perfusion pressure decreased 40-54% (p less than 0.01 for both). Furosemide did not significantly reduce mean arterial blood pressure but slightly reduced mean intracranial pressure in each group. Thiopental reduced both mean arterial blood pressure and intracranial pressure in both groups. The effect on intracranial pressure was pronounced in Group II, in which mean arterial blood pressure fell by 18% (p less than 0.05) and mean intracranial pressure decreased 50% (p less than 0.01), whereas in Group I mean arterial blood pressure was reduced by 16% and mean intracranial pressure dropped 23% (p less than 0.05 in each).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3354013 TI - Local intra-arterial fibrinolytic therapy in acute carotid territory stroke. A pilot study. AB - The possibility that intra-arterial local infusion of fibrinolytic agents may achieve recanalization of previously occluded carotid territory arteries in acute stroke was tested in a prospective angiography-based open pilot study at two centers. Fifteen of 20 patients with acute symptoms (mean treatment-onset interval 7.6 hours) demonstrated complete recanalization; 10 of the 15 patients exhibited clinical improvement of varying degree by the time of hospital discharge. Four of the 20 patients suffered hemorrhagic transformation of the infarcted territory without clinical deterioration or demise. Because of the study format and the limited number of patients, dose responses for recanalization and risk relations were not established. We conclude that local intra-arterial fibrinolytic therapy may lead to cerebral arterial recanalization in acute carotid territory thrombotic stroke. The particular implications and limitations of this approach are discussed. PMID- 3354015 TI - Serial changes in focal hyperemia associated with hypertensive putaminal hemorrhage. AB - Seventeen separate xenon-enhanced computed tomographic images were performed in seven patients with hypertensive putaminal hemorrhage. Regional cerebral blood flow maps were then computed and assessed. All patients were categorized as being of good recovery potential, with moderate-sized hematomas, and all were treated conservatively. The regional cerebral blood flow assessments were scheduled within 4 days after, 2 weeks after, and less than 25 days after the ictus. The initial decrease in hemispheric blood flow ipsilateral to the side of the hematoma was calculated as the ratio of ipsilateral to contralateral hemispheric blood flow and was correlated with the size of the hematoma; that is, the larger the hematoma, the greater the decrease in the ratio of ipsilateral to contralateral hemispheric blood flow. The decrease persisted for 1 month. The mean of the ratio at 2 weeks after onset was 70%, the lowest during follow-up. All cases examined within 4 days after onset demonstrated perihematomatous focal hyperemia, or "luxury perfusion," which accounted for the delayed decrease. The same tissue that had previously shown hyperemia showed decreased regional cerebral blood flow 2 weeks after onset. Our results demonstrate that the luxury perfusion syndrome caused the secondary brain damage even in the cases that were in relatively good condition. The feasibility of treatment can be assessed by considering these results. PMID- 3354016 TI - Cerebral vasospasm and eclampsia. AB - We describe a patient who experienced focal cerebral and brainstem ischemia in the setting of postpartum eclampsia. Cerebral angiography showed spasm of large- and medium-caliber arteries. This case provides rare documentation that vasospasm may account for cerebral ischemia in eclamptic women with focal signs. This observation suggests that in such patients cerebral angiography may be informative and useful. PMID- 3354017 TI - Trends in mortality from cerebrovascular disease in France from 1968 to 1978. With reference to cardiovascular and all causes of death. AB - Cerebrovascular disease mortality in France during the period 1968-1978 was compared with cardiovascular and all other causes of death. Our study demonstrated a 25% decline in the age-adjusted cerebrovascular disease mortality rates in both sexes and particularly in the middle-aged groups. This decline is greater than that of the general causes of mortality, which was on the order of 20%. It parallels the decline in congestive heart failure mortality but differs from that of ischemic heart disease. Nevertheless, despite the increase in the proportion of elderly people in the population, the total number of deaths from cerebrovascular diseases has remained almost unchanged, although the deaths occur at a higher age than previously. If this trend is confirmed, cerebrovascular diseases will remain one of the more frequent causes of death in the elderly and thus a social problem of crucial importance. PMID- 3354018 TI - Response time of stroke patients to a visual stimulus. AB - We used a computer program to test response time among stroke patients in a clinical setting. Visual stimuli were presented to 82 hospitalized stroke patients, to 21 hospitalized controls, and to 76 nonhospitalized controls. Stroke patients had longer mean response times than controls. Patients with right hemispheric lesions had longer response times than those with left hemispheric lesions when the stimuli were presented on the left. The corresponding phenomenon of longer response times in patients with left hemispheric lesions to stimuli presented on the right was not observed. Patients with right hemispheric lesions with visual hemineglect had a longer mean response time than those without visual hemineglect when the stimuli were presented on the left or centrally, whereas the patients with right hemispheric lesions without neglect had a mean response time similar to that of patients with left hemispheric lesions. PMID- 3354019 TI - Attenuation of postischemic cerebral hypoperfusion by the 21-aminosteroid U74006F. AB - The ability of the nonglucocorticoid 21-aminosteroid U74006F, a potent inhibitor of iron-dependent lipid peroxidation, to antagonize progressive brain hypoperfusion after a 5-minute episode of global brain ischemia was examined in alpha-chloralose-anesthetized cats. Immediately after a 5-minute episode of near total tourniquet-induced brain ischemia, cortical blood flow returned to normal or above normal. Thereafter, cortical blood flow fell progressively to a level 71.7% below normal by 3 hours after ischemia. In contrast, in cats that received 1 mg/kg i.v. U74006F 15 minutes after the ischemic episode, cortical blood flow remained significantly greater than that seen in vehicle-treated cats. At 3 hours, cortical blood flow had declined by only 45.7% (p less than 0.04 compared with vehicle). In addition, U74006F treatment significantly improved postischemic maintenance of blood pressure and recovery of somatosensory evoked potentials and reduced postischemic arterial blood acidosis. U74006F had no effect on cortical blood flow, somatosensory evoked potentials, or blood pressure in nonischemic cats. Our results suggest that U74006F may be useful in the early treatment of global cerebral ischemia. PMID- 3354020 TI - Transesophageal two-dimensional echocardiography in young patients with cerebral ischemic events. AB - Using transesophageal echocardiography, cardiac structures can be imaged with high resolution. The aim of our study was to evaluate whether transesophageal echocardiography is superior in detecting mitral valve prolapse and other cardiac abnormalities compared with transthoracic echocardiography in an age-matched control group and in young patients with cerebral ischemic events (patient group). Forty patients with cerebral ischemic events (mean age 35.2 years) and 29 controls (mean age 30.4 years) were examined using both methods. Transthoracic and transesophageal echocardiography showed a significantly higher incidence of mitral valve prolapse in the patient group compared with the control group (p less than 0.001). By means of transesophageal echocardiography, it was possible to measure highly significant bulging in both the anterior and the posterior mitral leaflet in the patient group compared with the control group (p less than 0.001), and the thickness of the mitral leaflets was significantly higher in the patient group. In 9 of 20 (45%) patients with normal transthoracic echocardiograms, transesophageal echocardiography showed pathologic findings. We found transesophageal echocardiography to be a sensitive method for detecting mitral valve prolapse as well as valve changes and other cardiac abnormalities not detectable by conventional echocardiography. Our study underlines the role of mitral valve prolapse in young stroke patients as a relevant risk factor and emphasizes the importance of changed mitral valve morphology. PMID- 3354021 TI - Prostaglandin concentrations in cerebrospinal fluid of rabbits under normal and ischemic conditions. AB - Clinical studies have demonstrated elevated levels of both arachidonic acid and prostaglandins in the cerebrospinal fluid of humans after ischemic stroke and subarachnoid hemorrhage. Such increases in free fatty acid, arachidonic acid, and prostaglandin concentrations suggest excessive production and accumulation of these substances in the ischemic brain. We used a rabbit model of ischemic infarction to examine the relation between controlled central nervous system ischemia and cerebrospinal fluid prostaglandin levels. We found that following stroke PGF2 alpha and not PGD2 was the predominant prostaglandin present in the cerebrospinal fluid. PGF2 alpha also underwent the largest percent increase over control prostaglandin concentrations. This is similar to human and dog cerebrospinal fluid studies, which demonstrate PGF2 alpha as the predominant prostaglandin following ischemic injury. The lack of PGD2 elevation under ischemic conditions may suggest that the rabbit model is more like stroke in humans than the rat or gerbil models. Our preliminary work demonstrates that it is practical to study postischemic prostaglandin changes in cerebrospinal fluid rather than in brain tissue in a rabbit model of central nervous system ischemia. PMID- 3354022 TI - Intra-aneurysmal pressure measurements in experimental saccular aneurysms in dogs. AB - Intra-aneurysmal pressure was studied in an experimental model of saccular aneurysm in dogs, using a vein pouch grafted onto a common carotid arterial bifurcation. The mean and the pulse pressures were recorded simultaneously from within the aneurysm and within the common carotid artery, before and after 50% proximal carotid artery stenosis. These experiments were performed under systemic normotension, hypotension, and hypertension. Normal data suggest that mean intracarotid and intra-aneurysmal pressures are similar and relate in a nearly linear fashion to mean arterial pressure. However, after 50% stenosis, the data had a cubic relationship, the reduction of pressure occurring only in the middle range of mean arterial pressure. Both intra-aneurysmal and intracarotid pulse pressures displayed less dependence on mean arterial pressure. However, sigmoid curves also were observed with the pulse pressures after 50% proximal common carotid artery stenosis. In all cases, after 50% stenosis, the rate of increase of the pulse pressures with mean arterial pressure was greater for higher mean arterial pressures. Our preliminary data indicate that a detailed study of intra aneurysmal pressure and blood flow in relation to systemic variables such as mean arterial pressure, cardiac output, and peripheral resistance may not only suggest improved means of managing patients with intracranial aneurysms, but also may raise the possibility that, under certain conditions, higher intra-aneurysmal pressures may be induced by downstream stenosis. PMID- 3354023 TI - A new model of brainstem ischemia in dogs. AB - A new model of brainstem ischemia in dogs is described. The perforating arteries arising from the posterior cerebral arteries as far as the bilateral junctions with the posterior communicating arteries were occluded using a subtemporal approach to the region of the interpeduncular cistern. Infarction of the posterior thalamus, subthalamus, midbrain, and upper pons was consistently produced. The dogs survived for greater than 1 week while exhibiting such clinical symptoms as disturbance of consciousness, tetraparesis, oculomotor paralysis, respiratory abnormalities, bradycardia, and arrhythmia. The clinical features and extent of infarction observed in this model closely resemble those of rostral brainstem infarction in human stroke. The model may be useful in studying the pathophysiology of brainstem ischemia. PMID- 3354026 TI - Glial swelling during extracellular acidosis in vitro. AB - Intracellular and extracellular acidosis may determine the ultimate outcome for brain tissue in cerebral ischemia. An extracellular acidosis that occurs in the penumbra zone was investigated in vitro as to its role in the formation of cytotoxic cell swelling. For that purpose, C6 glioma cells or primary cultured astrocytes were suspended in normal isotonic medium in normoxia during acidification to a final pH of 6.2. The cell volume response was determined by flow cytometry using hydrodynamic focusing, which allows one to recognize changes in cell size of less than 1%. A threshold pH of 6.8 was found that had to be crossed to induce cell swelling by acidosis. Once pH fell below this threshold, the increase in cell size appeared to be an all-or-nothing phenomenon. The cells rapidly assumed a final cell size of 115% of normal in the case of C6 glioma or of 118% in the case of primary cultured astrocytes independent of the actual level of acidosis or the duration of exposure. Acidosis-induced glial swelling could be significantly attenuated by 1) addition of amiloride, 2) administration of acetazolamide, or 3) replacement of bicarbonate buffer against N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Replacement of extracellular Na+ by choline chloride led to complete prevention of the acidosis induced cell swelling. Taken together, the findings strongly indicate a central involvement of Na+/H+ and Cl-/HCO3- exchange mechanisms in the development of cell swelling under these conditions. Activation of the Na+/H+ antiporter can be considered an attempt to maintain a normal intracellular pH at the expense of an abnormal cell volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3354025 TI - Bioenergetics of different brain areas after experimental subarachnoid hemorrhage in rats. AB - We studied energy metabolism after experimental subarachnoid hemorrhage in rats. Four different cerebral areas were tested: frontal cortex, occipital cortex, hippocampus, and brainstem. Vmax of the following enzymatic activities was evaluated: in the homogenate: hexokinase, phosphofructokinase, and lactate dehydrogenase for the glycolytic pathway, and glucose-6-phosphate dehydrogenase for the hexose monophosphate shunt; in the purified nonsynaptic mitochondria: NAD+-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase for the Krebs cycle, and cytochrome oxidase for the electron transfer chain. We also evaluated some parameters related to the respiration of nonsynaptic mitochondria (State 3, State 4, uncoupled state, respiratory control ratio, and ADP:O ratio). Subarachnoid hemorrhage did not significantly affect Vmax of the enzymatic activities related to anaerobic and aerobic metabolism; however, mitochondrial respiration was affected, particularly in the presence of NADH-producing substrates (glutamate + malate). PMID- 3354027 TI - Benign disappearance of ventricular thrombus after embolic stroke. A case report. AB - The source for a patient's middle cerebral artery territory embolic stroke was found by echocardiography to be a left ventricular cardiac thrombus. The apical mass was large, pedunculated, and moved with systole into the ventricular cavity. The absence of ventricular dyskinesia was thought to favor a tumor, and surgery was considered before repeat echocardiography showed disappearance of the mass, making thrombus the likely diagnosis. No further embolic events occurred during or since the disappearance of the thrombus while on anticoagulation therapy. Serial echocardiography for change in or disappearance of a ventricular mass may be critical in distinguishing thrombus from tumor. PMID- 3354024 TI - Brain eicosanoid levels in spontaneously hypertensive rats after ischemia with reperfusion: leukotriene C4 as a possible cause of cerebral edema. AB - The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane B2 and 6-keto prostaglandin F1 alpha levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfusion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C4 levels. That the increased brain water content was causally related to an increase in leukotriene C4 was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C4 and brain water contents after reperfusion. Our results indicate that leukotriene C4 is closely associated with an induction of ischemic cerebral edema. PMID- 3354028 TI - Medical treatment of transient ischemic attacks: does it influence mortality? AB - All randomized studies published on the medical treatment of transient ischemic attacks in which controls received no treatment or placebo and in which mortality was reported were reviewed. Using the odds ratio method, we analyzed the results to determine if treatment had an effect on expected mortality. Studies were analyzed separately according to the treatment modality used. Chronic anticoagulation was used in four studies and platelet inhibitors in 12 (14 trials). This meta-analysis showed that neither treatment modality significantly reduces mortality. Chronic anticoagulation may have an adverse effect, and even though platelet inhibitors appeared to reduce mortality, no significance can be demonstrated, and the 95% confidence intervals did not allow us to rule out the possibility, albeit small, of an adverse effect or no effect at all. PMID- 3354029 TI - Effect of nimodipine on blood pressure in acute ischemic stroke in humans. AB - Nimodipine is currently under investigation for the treatment of acute stroke. Although relatively specific for the cerebrovasculature, acute reductions in blood pressure after a dose may adversely affect neurologic outcome. We studied 29 consecutive acute ischemic stroke patients treated with placebo (n = 9) or either 120 (n = 10) or 240 (n = 10) mg/day of nimodipine. Blood pressure was recorded before and 30 and 60 minutes after a dose for the first 8 days. Ten neurologic physicians were asked to predict the treatment group (placebo or drug) of randomly selected patients based on blood pressure results. Only those patients on 240 mg/day of nimodipine had significant decreases in blood pressure after a dose (p less than 0.001); however, these were minimal (average 10 mm Hg systolic). Only 26 of 48 treatment predictions (54%) were correct. At the studied doses, nimodipine has a minimal effect on blood pressure in the acute stroke period. PMID- 3354030 TI - Heparin anticoagulation in acute brain ischemia. PMID- 3354031 TI - Resumption of anticoagulation during hypertensive cerebral hemorrhage with prosthetic heart valve. PMID- 3354032 TI - Resumption of anticoagulation after intracranial bleeding in patients with prosthetic heart valves. PMID- 3354033 TI - Atrial septal aneurysm as a cause of cerebral embolism in young patients. PMID- 3354034 TI - Computers and nursing: the five W's. PMID- 3354035 TI - Effect of preoperative shampoos on resident scalp flora. PMID- 3354036 TI - The manager as cheerleader. PMID- 3354037 TI - Theatre nursing in Scotland. PMID- 3354039 TI - Platelet membrane glycoprotein changes during the preparation and storage of platelet concentrates. AB - Previous studies of platelet membrane glycoproteins during blood bank storage have reported conflicting results. This study assessed two major plasma membrane glycoproteins (GP Ib and GP IIb), an alpha-granule membrane protein (GMP-140), and the concentration of platelet membrane microparticles in cell-free plasma during routine hospital blood bank platelet storage. 125I-monoclonal antibody binding was used to measure membrane glycoproteins on the surface of intact platelets and to measure the concentration of membrane microparticles in cell free plasma. Platelet concentrates were stored at room temperature in polyolefin bags for 7 days. In this blood bank, two types of rotators are routinely used for platelet concentrate storage: a 2-rpm circular tumbler rotator and a 6-rpm elliptical rotator. Different results were obtained with the rotators. With the tumbler rotator, there was no loss of platelets and antibody binding to GP Ib remained normal. With the elliptical rotator, one third of platelets were lost into clumps during storage, and a 50 percent decrease of antibody binding to GP Ib occurred in the remaining single platelets. There was no loss of antibody binding to GP IIb with either rotator. Antibody binding to GMP-140 increased equally in both rotators indicating that the remaining single platelets had secreted about 16 percent of their alpha-granule contents. The plasma concentration of platelet membrane microparticles was greater in the bags stored in the elliptical rotator. These results indicate that it is possible to maintain the normal concentration of platelet membrane glycoproteins Ib and IIb during 7 days of room-temperature blood bank storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 3354038 TI - Approaches to preventing or reversing platelet alloimmunization using animal models. AB - Animal transfusion models were established to assess treatment programs for preventing or reversing platelet alloimmunization. Five control baboons given weekly transfusions of radiolabeled platelets from a single unrelated donor became immunized after an average of 2.4 +/- 2.1 transfusions. Similarly, 18 of 21 (86%) dogs given up to eight platelet transfusions from a single unrelated donor became immunized after an average of 2.3 +/- 1.7 transfusions. In six of seven baboons, prednisone or antithymocyte globulin alone or in combination effectively delayed platelet alloimmunization. In contrast, only two of 12 (17%) dogs given prednisone or antithymocyte serum (ATS) resisted alloimmunization. Neither splenectomy nor cyclophosphamide prevented alloimmunization in the baboon. In addition, attempts to reduce the immunogenicity of transfused platelets by inactivating the contaminating leukocytes with gamma radiation or by giving leukocyte-poor platelets were of no benefit in dogs. Reversal of platelet alloimmunization was achieved in two of three dogs treated with ATS and procarbazine hydrochloride. However, neither splenectomy, cyclophosphamide, ATS plus prednisone, nor vincristine sulfate produced any improvement. These studies show that the highly immunogenic nature of platelet transfusions in animals makes feasible the study of the prevention and reversal of platelet alloimmunization. PMID- 3354040 TI - A chloroquine elution technique for platelet serology. AB - The authors describe a prototype elution method employing chloroquine, a quinoline derivative, to elute IgG antibodies from the platelet surface. This chloroquine elution technique is relatively easy to perform and is effective in the removal of alloantibodies from the platelet surface. Eluted alloantibody was immunologically active once the chloroquine was removed from the eluate. The major advantage of this technique is that serologic testing of platelets after elution is possible, as 50 percent of the platelets remain after exposure to hypertonic acid chloroquine solution. Antigens on the platelet surface maintained their antigenicity subsequent to treatment, although measurable reductions in PIA1 reactivity occur. The elution technique was also successful in removing IgG from the platelet surface in patients with diseases involving elevated levels of platelet-associated IgG. PMID- 3354041 TI - Patient-related blood drives. AB - Ten patient-related blood drives were evaluated and compared to five other blood drives. The patient-related blood drives were easier to organize, more fruitful, and more satisfying for the donors and workers. The authors suggest a role for patient-related blood drives in the present recruitment system and discuss how hospitals and blood centers can coordinate their efforts to have this type of blood drive. Finally, it is suggested that patient-related blood drives can increase recruitment, especially in large metropolitan areas that suffer from chronic blood shortages. PMID- 3354042 TI - Density gradient isolation of peripheral blood mononuclear cells using a blood cell processor. AB - Large numbers of mononuclear cells (MNC) are needed for hematologic reconstitution using peripheral blood stem cells. The possibility of isolating those cells by discontinuous Ficoll-diatrizoate density gradient centrifugation in two blood cell processors (the Haemonetics V50 [V50] and the Cobe 2991 [2991]) were examined. Buffy coats from peripheral blood containing 6.23 X 10(8) MNC were separated in the V50, resulting in a recovery of 75 percent. The purity of the cells, defined as the percentage of lymphocytes and monocytes among all leukocytes, was 95 percent. With larger cell loads (3 to 7 X 10(9) MNC), the yield was higher in the V50 than in the Cobe 2991 (92 versus 75%). After separation in the V50 or the 2991, the cloning efficiencies of hematopoietic progenitor cells (CFU-GM and BFUe) were not different from those of cells isolated on 5 ml Ficoll-diatrizoate gradients in centrifuge tubes. Both leukapheresis and MNC separation can be carried out with the same bowl and tubing set in the V50. With that approach, an average of 6 X 10(9) MNC were processed in 16 experiments. An average recovery of 82 percent with 95 percent purity was achieved. The authors conclude that, in terms of simplicity of operation, cost effectiveness, and maintenance of sterility, the V50 may be better suited than the 2991 for the purification of MNC from peripheral blood. PMID- 3354043 TI - Five-week red cell storage with preservation of 2,3 DPG. AB - The 2,3 diphosphoglycerate (2,3 DPG) content of red cells stored in current anticoagulant-preservative products decreases rapidly after the first few days of storage, and by 3 weeks the red cells are essentially depleted of 2,3 DPG. Because ascorbic acid and ascorbate-2-phosphate (A-2-P) are effective in maintaining erythrocyte 2,3 DPG during liquid preservation, ascorbate was stabilized through autoclaving and subsequent storage by adding it as the trisodium salt of A-2-P to a phosphate-adenine-saline solution at a pH of 8.5 to 9.0. Red cell concentrates prepared from blood drawn into citrate-phosphate double-dextrose were supplemented with the A-2-P additive solution (AS-4) and studied in vitro and in vivo. Mean 2,3 DPG values for 22 units were 147.6, 113.5, and 82.3 percent of initial value after storage for 3, 4, and 5 weeks, respectively. Maintenance of 2,3 DPG was at the expense of adenosine triphosphate (ATP), which fell to as low as 22.2 percent of initial value after 5 weeks. Despite the low ATP values, the 24 hour 51Cr-labeled red cell recoveries averaged 80.8 and 74.1 percent after 4 and 5 weeks of storage, respectively. The AS-4 system provides a red cell product with acceptable viability and improved oxygen off-loading function. PMID- 3354044 TI - Loss of red cell alloantibodies over time. AB - The loss of red cell alloantibodies over time was analyzed in 160 patients with 209 antibodies retested 1 to 60 months after initial identification. The mean follow-up consisted of 3.6 specimens taken over 18 months. Twenty-nine percent of clinically significant and 72 percent of clinically insignificant antibodies were not detected on at least one follow-up screening. Anti-Jka and anti-C were lost in 59 and 45 percent of cases, respectively. No significant differences in overall antibody loss were found according to sex, diagnosis, or the presence of multiple antibodies. Patients under 20 years of age may be more likely to lose significant antibodies. Pretransfusion review of previous records is vital for the prevention of delayed hemolytic transfusion reactions, because of the high number of clinically significant antibodies that are undetected in subsequent routine screening. PMID- 3354045 TI - Quality assessment of transfusion practice in elective surgery. AB - A program of quality assurance (QA) was adopted to improve blood transfusion practice in elective surgery at a large urban hospital. For this purpose, a cooperative multidisciplinary group was formed, key indicators were identified, and an organization was set up. Data collected by this organization in the 1-year period needed for implementation of the program indicated that blood misuse was common practice. In fact, overrequest, overtransfusion, excessive reconstitution of whole blood (i.e., concurrent transfusion of red cells and fresh-frozen plasma), and underuse of predeposit were found in all ten surgical departments of the hospital. In a pilot study, data were collected from one surgical department during and after the implementation phase of the QA program; comparison of these data showed a postimplementation reduction of about two thirds in overtransfusion, whereas overrequest, reconstitution of whole blood, and predeposit rates remained unchanged. These results prompted continuation of the program in order to reach a definitive evaluation of its effectiveness. PMID- 3354046 TI - Red cell tolerance of admixture with heated saline. AB - Red cell stability in the face of thermal stress has been evaluated only in the setting of prolonged incubation. This study was conducted to determine red cell tolerance of rapid mixture with heated saline, which exposes red cells to heat only until thermal equilibration, which is a matter of seconds. Half-units of 35 day-old red cells stored in CPDA-1 were mixed at 6 to 10 degrees C in the blood container with an equal weight of 60, 70, or 80 degrees C saline. This resulted in mean mixture temperatures of 30.9, 37.5, and 42.6 degrees C, respectively. Controls consisted of the same mixture, but with 6 to 10 degrees C saline. The red cells in the mixtures were assessed for osmotic fragility, and the supernatant was examined for plasma hemoglobin and potassium. Neither osmotic fragility curves nor supernatant hemoglobin or potassium changed significantly with saline temperatures of 60 or 70 degrees C. When 80 degrees C saline was used, osmotic fragility, supernatant hemoglobin, and potassium all increased significantly (p less than 0.01) over control values. Red cells tolerate rapid mixture with 70 degrees C saline without hemolysis or change in osmotic fragility. PMID- 3354047 TI - A near-fatal reaction during granulocyte transfusion of a neonate. AB - Although reactions to granulocyte transfusions in neonates are rarely reported, we observed a near-fatal pulmonary reaction, presumably due to white cell antibodies, in a neonate with Rh hemolytic disease. The hemolytic disease was being treated with exchange transfusions, and at 2 days after the infant's birth, bacterial sepsis was suspected and granulocyte transfusions were begun. The first granulocyte transfusion (Day 3) was uneventful. Five minutes after the beginning of the second granulocyte transfusion (Day 4), severe respiratory distress, hypotension, bradycardia, cyanosis, and acidosis suddenly occurred. The infant's serum obtained after the reaction contained granulocytotoxic and B lymphocytotoxic antibodies that reacted with leukocytes from the second granulocyte donor. Antibodies could not be detected either in the initial infant serum or in maternal serum. However, an antileukocyte antibody was present in the serum of a parous woman donor. We used plasma from this woman to prepare reconstituted whole blood for the exchange transfusion that we performed immediately preceding the second granulocyte transfusion. Despite the sequence of events, an irrefutable cause-and-effect mechanism could not be established because the properties of the donor and neonatal antibodies were similar, but not identical. However, this catastrophic event emphasizes both the potential for adverse effects of granulocyte transfusions in neonates and the need for caution when transfusing blood from parous women. PMID- 3354048 TI - Life-threatening autoimmune hemolytic anemia in a patient with the acquired immune deficiency syndrome. AB - Increasing numbers of patients are being seen with the acquired immune deficiency syndrome (AIDS). An abnormal serology with a positive direct antiglobulin test has been observed in these patients and is usually not thought to contribute to significant clinical morbidity. We describe a patient with AIDS who presented with a severe hemolytic anemia which was not distinguishable clinically and serologically from the idiopathic form of autoimmune hemolytic anemia. PMID- 3354049 TI - The global distribution of human immunodeficiency virus type 2 (HIV-2) infection. AB - We reviewed published reports of infection with human immunodeficiency virus type 2 (HIV-2) to provide a picture of its geographic distribution, pathogenicity, modes of transmission, and risk to the blood supply. Since the first reports in 1986, 627 HIV-2-seropositive persons have been reported; 604 of these were in natives of West Africa. Acquired immunodeficiency syndrome (AIDS) had developed in 42 patients, while 8 patients had AIDS-related complex. Transmission by sexual intercourse was the usual reported mode of spread. The modes of transmission of HIV-2 are thought to be the same as those for HIV-1, but perinatal transmission and transmission by sharing of needles among intravenous drug abusers have not yet been reported. The virus has not been identified in blood donors in the United States or West Germany, but two HIV-2-infected blood donors were reported in France. Further epidemiologic studies are needed to define the spectrum of disease, modes of transmission, and risk of HIV-2 to the blood supply. PMID- 3354050 TI - Questionable value of saline prepared granulocytes in the treatment of neonatal septicemia. PMID- 3354051 TI - Commercially obtained AB serum causing unacceptably high ionic strength in LISS techniques. PMID- 3354052 TI - Inactivation of HIV in antithrombin-III concentrate by pasteurization. PMID- 3354053 TI - New approaches to an old problem. Refractoriness to platelet transfusions. PMID- 3354054 TI - Efficacy of praziquantel against Schistosoma nasale infection in cattle. AB - Cattle naturally infected with nasal schistosomiasis were treated with a single oral dose of praziquantel at 20 mg/kg body weight. The drug was highly effective causing a considerable reduction in egg counts, cessation of clinical signs and progressive regression of the nasal granulomatous growths. PMID- 3354055 TI - Epidemiology of ovine helminthiasis in Haryana, India. AB - Tracer lambs were used to study the pasture contamination with infective stages of helminth parasites during one annual cycle in a subtropical climate. Post mortem worm counts indicated that low infections with Haemonchus contortus occurred throughout the year except in June. However, twenty five or more H. contortus per lamb were recorded in January, April, May and August. Trichostrongylus colubriformis infection was detected throughout the year and 150 or more worms per lamb were recorded during January to May and in August. Anoplocephalids were recorded from the lambs throughout the year but had no seasonal pattern. Low infections with Oesophagostomum columbianum and Trichuris ovis were observed. The faecal egg counts from the permanent flock with whom the tracer lambs were grazed revealed heavy to mild worm burdens throughout the year. Coproculture indicated that H. contortus predominated from the second fortnight of May to December except in the second fortnight of July. Infection with T. colubriformis was more severe from January to the first fortnight of May and in the second fortnight of July. Negligible infections with O. columbianum, Bunostomum trigonocephalum, Gaigeria pachyscelis and Dictyocaulus filaria were also observed. Biohythergraphs prepared for H. contortus and T. colubriformis showed differences between observed and expected results. It is suggested that for realistic biohythergraphs related parameters in addition to rainfall and temperature should also be considered. PMID- 3354056 TI - Efficacy of different adjuvants to potentiate the immune response to mycoplasma strain F-38. AB - A study was carried out to determine the efficacy of different adjuvants in enhancing antibody response to sonicated F-38 antigens. Goats were immunised against CCPP using antigens incorporated in Freund's incomplete adjuvant (IFA), saponin, aluminium hydroxide gel and buffered saline (PBS) respectively. Antibody responses were determined. The goats were challenged four months after immunisation to assess their immune status. Two of eight goats given antigen in PBS, six of 10 goats given antigen in aluminium hydroxide, seven of eight goats given antigen in IFA and all 10 goats given antigen in saponin withstood the challenge. Saponin and IFA were similar in their immune potentiation ability and were superior to aluminium hydroxide. As IFA has been considered unsuitable for use in food animals saponin may prove valuable in vaccination of goats against CCPP caused by mycoplasma strain F-38. PMID- 3354057 TI - Bovine anaplasmosis in Jamaica. PMID- 3354058 TI - Sheep trypanosomiasis in Somalia. PMID- 3354059 TI - Zinc deficiency in sheep: field cases. AB - Zinc deficiency was diagnosed in a sheep farm in Khartoum Province; the young sheep and lambs were mostly affected. Skin lesions, depression, wool eating, flexed knees and a markedly stiff gait were observed. Histopathology of the skin revealed mainly hyperkeratosis accompanied sometimes by parakeratosis. The animals responded rapidly to oral administration of zinc oxide. PMID- 3354060 TI - Clinical zinc and copper deficiencies in cattle of western Sudan. AB - Clinical cases of both Zn and Cu deficiencies are reported in a cattle farm in Kordofan Region of the Sudan after drought. The animals showed general weakness, stunted growth, infertility, parakeratosis and achromotrichia. There was macrocytic hypochromic anaemia and low Cu and Zn concentrations in sera. The condition was more prevalent in zebu-Friesian crosses than the local breeds. Drought and marginal or low Cu and Zn content in pasture may be the predisposing factors. PMID- 3354061 TI - Effects of supplementary feeding around lambing time on the productivity of Javanese thin-tail ewes. AB - The extent to which ewe reproduction could be improved by supplementary feeding around lambing time was investigated with four groups each of 16 ewes which were run continuously with fertile rams until they had lambed three times. One group was fed at a maintenance level throughout and the other three groups were given supplementary feed during the last four week of each pregnancy only, or during the last four weeks of pregnancy plus the first six weeks after each lambing, or during the last four weeks of pregnancy plus the first 12 weeks after each lambing. The average body weight of lambs weaned at 13 weeks of age increased (P less than 0.001) progressively from 6.0 to 9.1 kg with increasing duration of supplementary feeding. There were however no significant differences between treatment groups in mean interval between successive lambings (202 days), ovulation rate (2.26), litter size (1.58), lamb birth weight (1.8 kg), preweaning lamb mortality (37%) or number of lambs weaned per lambing (0.99). PMID- 3354063 TI - Influence of one- and two-stage biopsy-mastectomy procedures on psychologic adaptation of patients. AB - To investigate the psychologic adjustment of women undergoing radical mastectomy for cancer, we compared drug consumption (analgesics and sedatives) in the postoperative period and the time lag between operation and the first spontaneous observation of surgical wound in two groups operated according to different procedures. Group 1 (52 patients; mean age, 47 years) underwent a two-stage surgical treatment consisting of biopsy (local anesthesia) followed after 2-4 h by mastectomy (general anesthesia); in the interval patients were informed about ongoing procedures by the surgeon, who also pronounced some key words such as tumor, malignant disease, cancer. Group 2 (66 patients; mean age, 47 years) underwent biopsy and mastectomy in a single stage under general anesthesia. The relative risk (RR) of Group 1 vs Group 2 patients was calculated as regards both drug consumption and time of the first self-observation of the surgical wound. Our results seem to suggest that the two-stage procedure through special care given by the surgeon may result in a positive coping pattern and thus better acceptance of the mutilation. PMID- 3354062 TI - Anti-melanoma monoclonal antibody 225-28S: evaluation of toxicity in man. AB - To investigate possible undesirable effects due to the intravenous administration of a reagent of a xenogenic nature (monoclonal antibody 225-28S) in man, a toxicologic study was carried out on 85 patients with metastatic cutaneous melanoma. Two reagents were tested in this study: purified monoclonal antibody (MoAb) 225-28S and its F(ab')2 fragment. Purified MoAb was labelled with 131I and F(ab')2 fragment with 131I, or 123I, or 111In or 99Tc. The quantity of MoAb or F(ab')2 injected ranged from 14 to 750 micrograms, and the specific activity from 37.0 to 2116.4 MBq/mg. The total radioactivity injected varied from 25.9 to 891.7 MBq/mg. In addition to a careful clinical examination, the following tests were done to monitor possible adverse effects: blood glucose, azotemia, RBC, WBC, platelet count, serum creatinine, creatinine clearance, plasma electrolyte levels, serum proteins, albumin/globulin ratio, serum bilirubin, SGOT, SGPT, gamma GT, and CPK. These tests were done before the injection and on days 7 and 14. No patient experienced adverse general effects like fever, nausea, vomiting or allergic reactions. None of the aforementioned hematometric and biochemical tests showed significant variations compared with the initial values. It is concluded that a single injection of these reagents at the dosages tested is completely atoxic. PMID- 3354064 TI - Estrogen and progesterone receptors as prognostic factors in breast cancer. AB - The relation between estrogen receptors (ER) and/or progesterone receptors (PgR) and some clinical factors such as tumor size, axillary node involvement, histological tumor grade, and disease-free interval (DFI) in 500 patients with operable (TNM stage I-III) breast cancer was studied. ER-positive (ER+) tumors were commoner in older patients, whereas PgR-positive (PgR+) tumors were similarly distributed within the age groups. The concentration of ER+ protein also increased with age in contrast to PgR+ protein concentration. However, receptor status was not associated with menopausal status independently of age. Axillary node involvement influenced neither ER nor PgR status, but there was a statistically significant relation between tumor size and positivity of ER or PgR. There was no association between histologic tumor grade and either steroid receptor phenotype. DFI was longer in patients with ER+ than those with ER- tumors, independently of axillary nodal status. The positivity of PgR in patients with ER+ tumors contributed to an even longer DFI, suggesting that the combination of ER/PgR is a better indicator of DFI than ER or PgR alone. PMID- 3354065 TI - A phase II clinical trial of flutamide in the treatment of advanced breast cancer. AB - An antiandrogenic agent flutamide was used in the treatment of one male and 14 female postmenopausal breast cancer patients. Only a mild and transient response was seen in 2 female patients. Therefore, flutamide cannot be used solely in the treatment of female postmenopausal breast cancer. PMID- 3354066 TI - Thymoma: a clinico-pathologic study based on newly developed morphologic criteria. AB - A retrospective study of 28 cases of thymoma classified according to Marino and Muller-Hermelink (cortical, medullary, mixed common, mixed with cortical predominance, mixed with medullary predominance thymoma) was undertaken to determine the existence of correlations between histology and clinical behavior. Cortical thymoma was observed in 11 cases (39.2%), mixed common thymoma in 9 (32.1%), mixed with cortical predominance in 5 (18%), and medullary thymoma in 3 (10.7%). In patients with cortical thymoma the tumor was always invasive (stages II and III according to Bergh), whereas medullary thymomas were noninvasive in 2 cases (stage I) and slightly invasive with a moderate infiltration of the capsule in the remaining case (stage II). Mixed common and mixed with cortical predominance thymomas displayed intermediate behavior. Twelve patients were affected by myasthenia gravis: 1 had medullary thymoma, 6 had mixed common thymoma, 3 had mixed thymoma with cortical predominance, and 2 had cortical thymoma. One patient with cortical thymoma had superior vena cava syndrome and 1 had erythroid hypoplasia; mixed common thymoma was associated with Cushing's syndrome in 1 patient. These data confirm previously reported observations (16) showing a higher degree of malignancy in patients with cortical thymoma. PMID- 3354068 TI - Parafollicular C-cell hyperplasia. Report of three cases in primary thyroid lymphomas. AB - Three cases of C-cell hyperplasia were observed in a series of 21 cases of primary thyroid lymphoma (PTL). The association is not well understood, since PTL is not included in the group of thyroid diseases which are known to cause C-cell hyperplasia. It may be interpreted as a compensatory reaction to diffuse and rapid destruction of most of the gland, or a "stimulation" related to the production of "bio-humoral" factors by neoplastic cells. PMID- 3354067 TI - Bladder cancer prognostic indices: analysis of 286 patients treated with radical radiation therapy. AB - From 1974 through 1982, 286 patients with histologically proven bladder cancer (Tis 8, T1 62, T2 109, T3 86, T4 21 NXMO) were treated with external irradiation after transurethral resection. Irradiation was given with 260 degrees arc technique photon beam from a Cobalt Unit; the tumor doses ranged from 52.5 to 65 Gy in 21-50 days, with a TDF between 75 and 110. The analysis was conducted with the log rank test on the cumulative percent survival (CPS) at 5 years. The study pointed out the importance of risk factors other than clinical stage on cumulative survival in bladder cancer. Prognostic factors associated with a relatively successful outcome (p less than 0.001) were the Karnofsky performance status (100 vs others) (CPS 75% vs 30%), the absence of ureteral obstruction on the initial intravenous pyelogram (CPS 50% vs 35%), a negative urine culture (CPS 60% vs 30%), normal bladder capacity (CPS 50% vs 35%), low-grade histology (CPS 65% vs 35%), and grossly complete resection (55% vs 40%). The data from this analysis should be taken into consideration when radical radiotherapy is considered in new clinical trials. PMID- 3354069 TI - What's going on in nerve sheath tumors? PMID- 3354070 TI - Ultrastructural changes suggestive of focal segmental glomerulosclerosis in atypical minimal change nephrotic syndrome. AB - In an attempt to recognize early stages of focal segmental glomerulosclerosis (FSGS) in patients with a clinical course suggesting a diagnosis other than minimal change disease (MCD) and normal histology, or minor, nondiagnostic changes on light microscopy (LM), we used a protocol for systematic and extensive electron microscopy (EM) examination of kidney biopsies obtained from such patients. By this method ultrastructural pathology was found in 8 patients. These changes were localized, involving only portions of single glomerular segments. The findings included mild to moderate increase of the mesangial matrix, focal wrinkling of the capillary basement membrane, and early obliteration of the normal architecture of individual capillary loops, as well as electron-dense deposits in a mesangial and subendothelial distribution. Of these 8 patients, 2 are at present in remission without therapy (in 1, following therapy with cyclophosphamide); 3 are in remission on steroid therapy; 1 developed massive proteinuria during pregnancy, after a spontaneous remission lasting almost 2 years; 1 patient advanced to terminal renal failure 3 1/2 years after biopsy; and 1 died of sepsis 1 month after biopsy. We believe that the ultrastructural changes found may represent early or mild FSGS and that the protocol described can add valuable information in clinically worrisome patients in whom renal histology appears normal. PMID- 3354071 TI - A rapid and simple method for electron microscopy of paraffin-embedded tissue. AB - A new rapid and simple method for electron microscopy of paraffin-embedded material is described. The paraffin-embedded tissue is deparaffinized in xylene, stained in a 0.01% toluidine blue/absolute ethanol solution, infiltrated in a propylene oxide/resin mixture, and embedded in epoxy resin. This quick method, which excludes rehydration, postosmification, and dehydration, takes about 3 h and produces results equal to previously described more laborious re-embedding techniques. PMID- 3354072 TI - Unusual nuclear inclusions in CNS macrophages of a man with encephalomyelitis and acquired immunodeficiency. PMID- 3354073 TI - Limitations of the usefulness of microvillous ultrastructure in distinguishing between carcinoma primary in and metastatic to the lung. PMID- 3354074 TI - Ultrastructural changes of glomerular basement membrane in IgA nephritis: relationship to hematuria. AB - Ultrastructural changes in the glomerular basement membrane (GBM) of 415 samples from 344 patients with IgA nephritis, were examined for potential relationship to hematuria. The GBM showed various alteration: splitting, thinning, membranolysis with swelling of the lamina rara externa and interna, forming of small projections, and rupture. These lesions were present in 48% of IgA nephritis and in 16% of the controls. In the IgA nephritis group, the patients with hemispherical mesangial dense deposits had the highest rate (60%) of capillary wall abnormalities. Such lesions were more frequent in patients biopsied during severe hematuria (80%) than in those biopsied without hematuria (33%), (p less than 0.01). It is assumed that the ultrastructural abnormalities of GBM may contribute to the clinical evidence of severe hematuria. PMID- 3354075 TI - Ultrastructure of renal adenoma. AB - Renal adenomas, defined as minute cortical foci of proliferating epithelium, are frequently occurring lesions reported to be present in 15%-22% of all adult human kidneys. They can often be found in kidneys with renal cell carcinoma. Their light microscopic structure makes it improbable that they should represent intrarenal metastases. The concept does not include clear cell foci. Ultrastructure of these cortical foci in human kidneys is not well known. A series of 10 intrarenal adenomas in carcinoma-bearing kidneys has been studied using tissue fixed rapidly after nephrectomy by perfusion with 2% glutaraldehyde. The results confirm their tubular origin. Ultrastructural markers of different segments of the nephron were demonstrated. Several of these markers might be present in each single case. The interpretation is that their ultrastructural characteristics do not indicate an origin from a special segment of the nephron. They may reflect an abnormal gene expression associated with the neoplastic change of the cell clone. Some changes are similar to those seen in cells from renal cell carcinoma, although not as prominent as in malignant cells. PMID- 3354076 TI - [Raw diet in cancer prevention]. PMID- 3354077 TI - [The Danish health survey 1982-1983. I. Collection of data by means of diaries]. PMID- 3354079 TI - [Hepatitis B in patients and staff at an institution for mentally retarded in 1985]. PMID- 3354080 TI - [The occurrence of Campylobacter pyloridis in patients with upper gastrointestinal dyspepsia]. PMID- 3354081 TI - [Small intestinal atresia. A congenital malformation]. PMID- 3354078 TI - [The Danish health survey 1982-1983. II. The validity of health diaries]. PMID- 3354082 TI - [Osteosynthesis of femoral shaft fractures in children]. PMID- 3354083 TI - [Echocardiography in a district hospital]. PMID- 3354084 TI - [The occurrence of HIV antibodies in Danish dialysis patients]. PMID- 3354085 TI - [Young drug addicts admitted to psychiatric hospitals in the county of Arhus 1975 1984. III. Social background factors]. PMID- 3354086 TI - [Pseudothrombophlebitis in a case of ruptured Baker's cyst]. PMID- 3354087 TI - [Fatal autoimmune hemolytic anemia probably induced by treatment with piroxicam]. PMID- 3354088 TI - [Periodic hypersomnia. A case of possibly traumatic origin]. PMID- 3354089 TI - [Abdominal angina]. PMID- 3354090 TI - [Campylobacter colitis with light microscopy demonstration of bacteria in colon biopsy]. PMID- 3354091 TI - [Raw food against cancer. A report from a study done by the Society for Alternative Medicine]. PMID- 3354092 TI - [Interaction between H2 receptor antagonists (cimetidine, ranitidine) and alcohol]. PMID- 3354093 TI - [Automatic data processing registration of postoperative wound infections. A prevalence study]. PMID- 3354094 TI - [Etiology of bacterial meningitis]. PMID- 3354095 TI - [Delivery in breech presentations. A retrospective review]. PMID- 3354096 TI - [Trigger finger in small children. Care material from an orthopedic surgery practice]. PMID- 3354097 TI - [Mercury poisoning. A rare disease in Denmark]. PMID- 3354098 TI - [Hypophosphatemia]. PMID- 3354099 TI - [Tendency to edema as the initial symptom of Cushing's syndrome]. PMID- 3354100 TI - [Repeated acute dystonia following administration of metoclopramide and fluphenazine]. PMID- 3354101 TI - [Shall asthma be treated by acupuncture?]. PMID- 3354102 TI - [False positive mammography in edema of the breast]. PMID- 3354103 TI - [Young drug addicts admitted to psychiatric hospitals 1975-1984. I. A retrospective epidemiological analysis]. PMID- 3354104 TI - [Myelomeningocele in Denmark]. PMID- 3354105 TI - [Blood pressure measurement and the roll-over test at the start of the 3d trimester as predictors of the development of pre-eclampsia]. PMID- 3354106 TI - [Hypomagnesemia as the cause of severe therapy-resistant hypocalcemia after extensive intestinal resection]. PMID- 3354107 TI - [Fetal bradycardia in the 29th week of pregnancy. A sequel to hypoxia or genuine arrhythmia?]. PMID- 3354109 TI - [Carcinoma of the lips, mouth, pharynx and larynx in Denmark 1943-1982. Cancer statistics No. 22]. PMID- 3354108 TI - [Ketamine in the treatment of severe therapy-resistant status asthmaticus]. PMID- 3354110 TI - [Autoimplantation of the parathyroid glands]. PMID- 3354111 TI - [Complications of the surgical treatment of benign thyroid diseases in a teaching department]. PMID- 3354112 TI - [Complications of 2,028 operations for benign thyroid disease. Quantitative significance of various risk factors]. PMID- 3354113 TI - [Healing time for fractures of the scaphoid bone]. PMID- 3354114 TI - [Sex education for teenage girls seeking abortion]. PMID- 3354115 TI - [Course and prognosis of hepatitis in infectious mononucleosis]. PMID- 3354116 TI - [Young drug addicts admitted to psychiatric hospitals in the County of Arhus 1975 1984. II. Addiction patterns, reasons for admission and course of treatment]. PMID- 3354117 TI - [Skin infection with atypical Mycobacteria. Swimming pool/aquarium granuloma]. PMID- 3354118 TI - Anesthesia penile tumescence test. AB - This article describes a simple method which we have found useful in helping to diagnose psychogenic impotence. PMID- 3354119 TI - Erectile dysfunction due to ectopic penile vein. AB - A total of 86/260 patients with erectile dysfunction had venous leakage as (joint) etiology. In 5 of 86 patients cavernosography showed pathologic cavernosal drainage only via an ectopic penile vein into the femoral vein. After ligation of this pathologic draining vessel, 4 of 5 patients regained spontaneous erectability. One patient with pathologic bulbocavernosus reflex latencies needed intracavernosal injection of vasoactive drugs for full rigidity. PMID- 3354120 TI - Cylinder problems with AMS 700 inflatable penile prosthesis. AB - Six cases of cylinder problems encountered in 1986 with the AMS 700 Silastic inflatable penile prosthesis (IPP) were studied in detail. The problems included 1 case of significant penile bending, the development of a cylinder tear, and several cylinder aneurysms. Possible causes of the problems are explored, along with possibilities for prevention of future problems. PMID- 3354121 TI - Radical cystectomy for historical and pathologic T1, N0, M0 (stage A) transitional cell cancer. Need for adjuvant systemic chemotherapy? AB - Of 695 patients who, in a five-year period, underwent cystectomy for bladder cancer, 32 (4.6%) proved to have historical and pathologic Stage T1 (Stage A) transitional cell cancer. Of these, 23 (72%) had grade 3 disease or higher. Overall, in 17 (53%) progression developed after follow-up of greater than or equal to 5 years. Moreover, in 10 (31%) of the patients systemic progression developed during follow-up; less than 50 per cent of the patients were projected to be free of systemic progression at ten years. DNA ploidy pattern analysis did not prove helpful in predicting disease outcome. Because effective systemic chemotherapy has become available in the form of M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin), it seems justifiable that patients who are considered to be candidates for cystectomy because of high-grade, multifocal T1 transitional cell cancer of the bladder also could be candidates for effective neo-adjuvant chemotherapy, in addition to those who usually are part of these protocols--namely, those with greater than or equal to T2 disease. PMID- 3354122 TI - Fibroepithelial polyp in a child. AB - Only 15 cases of fibroepithelial polyp in children have been reported in the world medical literature. Clinical differentiation between this tumor and a malignant ureteral tumor is difficult and often results in unnecessary nephrectomy. We report the sixteenth case of a child with fibroepithelial polyp of the ureter. The lesion was resected, and the kidney was preserved. Optimum treatment of this lesion mandates renal preservation in children. The rationale for this recommendation is explored. PMID- 3354123 TI - Traumatic renal artery dissection. AB - Hypertension consequent upon traumatic subintimal dissection of the renal artery is described in 2 cases. The pathogenesis and treatment of this uncommon condition are presented. PMID- 3354124 TI - Urethrovasocutaneous fistula. AB - We report a case of urethrovasocutaneous fistula in an elderly man. There were several possible etiologic factors in this case including: prior vasectomy and transurethral prostatectomy, urinary tract infection, and neurogenic bladder. PMID- 3354125 TI - Use of office colposcope to diagnose subclinical papillomaviral and other infections of male and female genitalia. PMID- 3354126 TI - The Edelman catheter. PMID- 3354127 TI - Leiomyoma of tunica albuginea of testis. AB - Leiomyoma is an uncommon lesion which may originate anywhere within the genitourinary system where smooth muscle is present. The third case of leiomyoma of the testicular tunica albuginea is reported, and other reports of genitourinary leiomyomas are reviewed. PMID- 3354128 TI - Stony testicle: case of calcific granulomatous orchitis. AB - A thirty-three-year-old man presented with a hard testicular mass considered preoperatively to be a malignant testicular tumor. Frozen section revealed calcific granulomatous orchitis, which does not appear to have been previously described in man. Granulomatous orchitis is an important differential diagnosis of testicular lesions. The hard nature of this particular lesion contributed to the preoperative diagnosis of malignancy. PMID- 3354129 TI - Pyelosinus extravasation and urinoma associated with malignancy. Computed tomography demonstration. AB - We report 3 cases of abdominal malignancy with urinary tract obstruction and pyelosinus extravasation. Urinomas were present in 2 cases. The computed tomographic findings are emphasized, including the distribution of the extravasated urine reflecting the partitioning in the perirenal space. The cases presented within an eighteen-month period suggest pyelosinus extravasation and urinoma formation may not be uncommon in malignant disease affecting the retroperitoneum and pelvis. PMID- 3354131 TI - Urinary extravasation during renal colic. PMID- 3354130 TI - Changes in detrusor contractility after incontinence surgery. AB - To study the effects of incontinence surgery on detrusor contractility, a group of 24 women who preoperatively voided without a detrusor contraction during voiding urethrocystometry were re-evaluated for detrusor contractility three months after surgery for stress urinary incontinence. Twelve women regained detrusor contractility during voiding and were able to resume spontaneous voiding after incontinence surgery. The remaining 12 patients, representing true detrusor atony, continued to void without a detrusor contraction, and the majority (10/12) needed prolonged postoperative bladder drainage prior to resumption of spontaneous voiding. Presence of reduced flow rates and absence of detrusor contraction during preoperative voiding indicated true detrusor hypotonicity. Two thirds of the patients voiding with normal flow rates but without a detrusor contraction during preoperative voiding regained detrusor contraction after incontinence surgery (p less than 0.05). PMID- 3354132 TI - Sleep environment crucial in NTP assessment. PMID- 3354133 TI - Use of transrectal Foley balloon tamponade in prostate biopsy hemorrhage. PMID- 3354134 TI - [Methodological bases for research on the vestibulo-ocular reflex]. PMID- 3354135 TI - [Prevention of antibiotic ototoxicosis]. PMID- 3354136 TI - [Endaural phonophoresis in treating inoperable forms of otosclerosis]. PMID- 3354138 TI - [Changes in the microcirculatory bed of children with acute and chronic maxillary sinusitis based on conjunctival biomicroscopy data]. PMID- 3354137 TI - [Possibility of the statistical prediction of the effectiveness of cryotherapy in chronic inflammatory diseases of the nasal cavity]. PMID- 3354139 TI - [Status and developmental outlook of ENT oncology in the USSR]. PMID- 3354140 TI - [Immunocorrective therapy of chronic tonsillitis patients]. PMID- 3354141 TI - [Functional metabolic activity of neutrophilic granulocytes in angina patients]. PMID- 3354142 TI - [Adenotomy in the combined treatment of acute maxillary sinusitis in children]. PMID- 3354143 TI - [Comparative analysis of cultured cancer and normal epithelial cells from human laryngeal mucosa]. PMID- 3354144 TI - [Carotid-cavernous anastomosis evoking a suspicion of an intracranial rhinogenic complication]. PMID- 3354146 TI - [Neurinoma of the external auditory meatus]. PMID- 3354145 TI - [Errors in the diagnosis of scleroma of the respiratory tract]. PMID- 3354147 TI - [Liquorrhea following a radical operation on the ear]. PMID- 3354148 TI - [Ameloblastoma of the maxillary sinus]. PMID- 3354149 TI - [Nasopharyngeal fibrolipoma in a child one month old]. PMID- 3354150 TI - [A large foreign body in the main bronchus]. PMID- 3354151 TI - [Simultaneous surgical intervention on the lung and larynx for different tumors]. PMID- 3354152 TI - [Grisel's disease after tonsillectomy]. PMID- 3354153 TI - [Integrative radiomodifying therapy of malignant oropharyngeal tumors]. PMID- 3354154 TI - [Threshold and suprathreshold audiometric research on railroad transport workers]. PMID- 3354155 TI - [Acute sensorineural hearing loss as a consequence of craniocerebral trauma]. PMID- 3354156 TI - Comparative efficacy of triclabendazole, nitroxynil and rafoxanide against immature and mature Fasciola hepatica in naturally infected cattle. AB - In two trials the fasciolicidal activities of triclabendazole, nitroxynil and rafoxanide were assessed in cattle naturally infected with predominantly immature stages of Fasciola hepatica. Tablets containing 900 mg triclabendazole were administered orally at a dose rate of 12 mg/kg bodyweight. Rafoxanide and nitroxynil were used at a dose rate of 10 mg/kg, rafoxanide being given orally and nitroxynil by subcutaneous injection. Based on faecal egg counts nine weeks after treatment the efficacies were calculated to be 100 per cent for triclabendazole and 95.0 per cent for nitroxynil in the first trial and 98.4 per cent for triclabendazole and 52.9 per cent for rafoxanide 15 weeks after treatment in the second trial. In the first trial five animals from each of the three groups were slaughtered and their fluke burdens counted. Compared with the untreated control group the reductions in the fluke burdens were 96.9 per cent in triclabendazole treated cattle and 76.4 per cent in the nitroxynil treated group. PMID- 3354157 TI - Relationship of calf antibody status to disease and performance. AB - Three tests were used to measure the circulating immunoglobulin in 381 purchased calves as they entered a commercial calf-rearing unit. A correlation of 0.64 was found between the zinc sulphate turbidity (ZST) test and a quantitative latex agglutination test (LAT) measuring IgG1 (P less than 0.001). A qualitative version of the LAT related poorly to the quantitative version. The proportion of plasma samples identified by the quantitative LAT as having an IgG1 concentration of less than 5 g/litre which were incorrectly identified as positives (greater than or equal to 5 g/litre) by the qualitative LAT was 0.65. The proportion of plasma samples identified by the quantitative LAT as having a IgG1 concentration of greater than or equal to 5 g/litre which were incorrectly identified as negative (less than 5 g/litre) was 0.11. There was no statistically significant relationship between plasma IgG1 concentration and initial liveweight, subsequent overall daily liveweight gain or disease incidence (P greater than 0.05). Calves treated for infectious disease, particularly respiratory disease after weaning, had statistically significantly lower liveweight gains than healthy calves (P less than 0.001). PMID- 3354158 TI - Evidence of louping ill and tick-borne fever in goats. PMID- 3354159 TI - Experiences in veterinary practice: knowledge comes but wisdom lingers.